Gass’ Atlas ot

MACULAR
DISEASES
Dedication

]b my parents, grandmother and siblings

Vj'pihrfu Chendraiah
Oafish a U iam iruinit
.M .fJ. СЬллЛпшф
fi. S. Рсшшргшл
Onrcibr Sucfrnnj Vinuta'pnd МящаЬл
for iheir unending love and failh in me

]b my teachers

/. fJoWdJrf jM f^JSS
Amod Citplti
for iheir inspiration and teaching

and la iheir spouses and children

M argy Алл С л и dffd (iiin ib i <5iJf Gupia
fohth Carlton, .Merirdr Dean ami Sujpu^frid
for supporting their careers and allowing me to borrow iheir lime

To my colleagues and friends

for selflessly sharing their cases and knowledge

lb our paltenls
for giving us ihe privilege of learning through ihem

C.MLiiLiM'kir.ini! EJib.ift Rii-^.l Gabbedy

BSmjpracni EdHun 4:.i.\ii: Kj-Jl
bJiiiMiJ AjiijJmtfjli Kintuci Li'.yh'II
l^ojL'cr Млъщегн): Jt-кTFinmpbuij'Arji-™Rjldf
Duign: Sk-w.m L.ickiryn
l.l> r.iгi..11 \L.iili:-'. c: (ill inn |!.i■
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-
Llu-u.ici'r Mnjtm^ |Уь.|л.it.I
!-.I .iii i■
.■. . (Jfytkjuoz Nalfun
^l.ii k > МапядсгЬI IUk,'L SAJ: Liapvtr Jchei/I кlau \lui.Lk
 VOLUME ONE
FIFTH EDITION

Gass’ Adas of

A N I T A A G A R W A L , MD
A s s o c i a t e P r o fe & S jp r o t О p h t h a l m o l o g y

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lau n d ers

British lib ra ry C ataloguing in IhLblicalion Data

j^garwal, Anita.
Cass' atlas o f m acular diseases. - 5tit cd.
1. M acula in tea Diseases Atlases.
E. Title El. Cass. ]. D on ald M. (Jo h n D on ald Ш , Ю2Й-2005
Stereoscopic atlas o f m acular diseases.
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 CONTENTS

VOLUM E ONE

.i k f c f l □ N1\flign П ] L\l E£ i JCT.V

i'cmi'ortk .tv
I-Vot/lJ Мир uti l'
i ’tv/jff Го i'iflh frjJfrron i.irir
Preface Го гЛв J-'irrt lirfifj'iwi ллт1
/л Hom’mbmnce of Or. .vn-'i

1 Normal LVlacula
Anita Agpwai
Anatomic Subdivisions . . 2
Clinical Appearance . . . . 2
Blood S u p p ly .............. . 2
Gross A n a to m y ........... .4
Histology...................... .6
Normal I'luorescein Angiographic Findings 10
References............................................... 16

2 im a g in g a n d E le c tr o p h y s i о lo g ic a l S m d ie s 17
Anihi Agarutal

l^athophysiologic and Histopathologic Bases for Interpretation of Fluorescein Angiography.. . , ь b 13

AbnormaIities of Blood ];low................................................................................................................. IS
Window defects (transmission hyperfluorescence) in the retina] pigment epithelium causing
focal hyperfluorescence......................................................................................................................... 20
Exudation and Fluorescein Staining...................................................................................................... 20
lesions that Obscure the Normal Retinal and Choroidal Fluorescence................................................. 46
FI no rescence о f E.esio ns t J nrel aLed to Changes in Vascu lar Fermea bil i t y ............................................... 46
Endocyanine Creen Angiography.............................................................................................................. 4S
Auto fluorescence. .....................................................................................................................................50
Optical Coherence'I'omography.............................................................................................................. 52
Ultrasonography.......................................................................................................................................52
Adaptive O p tic s .......................................................................................................................................56
Llectroretinogram ( L R G ) ......................................................................................................................... 56
Multifocal £ R C .......................................................................................................................................5S
KlecLro-Oculogram [E iO G j.......................................................................................................................60
References............................................................................................................................................... 60
3 Diseases Causing Exudative and I teuionhagic DeLachmenL
of the Choroid, Retina and Retinal Pigment epithelium 63
Atiiiii Ajgimuf

Mechanisms of Serous acid Hemorrhagic Disciform Detachment of the M a c u la .......................................64

Specific Diseases Causing Disciform Macular Detachm ent........................................................................66
Idiopathic Central Serous Chorioretinopathy...........................................................................................66
Age-ReEated Macular [Regeneration............................................................................................................92
Bawl ijm in ar Drusen and Maculaf Degeneration.................................................................................... 132
Idiopathic Choroidal Neovascularization ............................................................................................... 136
l^eripheral 1diopath ic 5ub-RPE ^eovascul arizatio n ................................................................................. 140
Angioid Streaks and Associated Diseases..................................................................................................142
1'seudoxanlitom a EEasticu m.................................................................. .................................................. 146
Sickle-Cell Disease and Other I Eemoglobinopathies...............................................................................I SO
Paget's Disease........................................................................................................................................ 152
Myopic Choroidal Degeneration.............................................................................................................154
Presumed Ocu lar El istopl as mosis Sy nd r o m e ..........................................................................................15tf
Idiopathic E’olypoidal Choroidal YascuIo p ath y.......................................................................................176
Unusual Causes of Choroidal Neovascularization.................................................................................... 17Й
Acute Occlusion of the Short Ciliary and Choroidal Arteries....................................................................17S
Acute Occlusion of the PrecapЦlary Arterioles and Choriocapil la ris .........................................................1H2
Disseminated intravascular Coagulopathy............................................................................................... 1S2
Mali gctaul 1Eypertensio n ........................................................................................................................1Й4
loxemia of Pregnancy............................................................................................................................. 1Й6
Collagen Vascular Disease........................................................................................................................1ЙЙ
Goodpasture's Syndrom e........................................................................................................ ...............IS a
Systemic Necrotizing Vasculitis (Wegener's CranuEomatosis and E.ymphoid Cranulom alosis).................. 1ЙЙ
Or^an Transplantation and Hem odialysis...............................................................................................190
Extrinsic and Intrinsic Embolic Obslrtiction of the Choriocapil la ris............................................ b . .. .190
Dysproleinemia Causing Serous Macular Detachment andRetinopathy..................................................... 192
Idiopathic LJveal Lffusion Syndrome....................................................................................................... 196
Primary Pulmonary Hypertension..........................................................................................................202
Suprachoroidal Hem orrhage.................................................... ............................................................. 204
References............................................................................... .............................................. ...............206

4 holds of the Choroid and Retina 213

Anita

Chorioretinal l-olds................................................................................................................................220
Optic Nerve Head Diseases Associated with Chorioretinalt-'olds............................................................... 22a
Retinal l:o ld s...........................................................................................................................................230
PosterlO^ M icrophthalm os.................................................................................................................... 232
Outer Retinal <Corrugations in Juvenile X-Linked Ketinoschisis................................................................ 234
Non accidental and Accidental Trauma.................................................................................................... 234
14>st Macular Translocation Su rg e ry.......................................................................................... b . . .234
References.............................................................................................................................................236

5 Heredodys trophic Disorders Affecting the Pigment Epithelium and Retina 239
Anita AgtiruwJ

best's Di s e a s e ....................................................................................................................................... 240

Autosom aI-Do in inan t Vitreoreti nochoro id o p a th y .................................................................................24 fl
AulosomaE-Dominant Microcornea Pod-Cone DystrophyCataract xvish Staphylom a.............................. 24S
Autosoma I-Elecessive EJestrophin o p ath y................................................................................................. 2S0
Multifocal Vi tel li form Lesions in Patients Without Evidence of Best's Disease.......................................... 152
Aulosom aI-[dominant E]attern Dystrophies of the E iP E ........................................................................... 254
Systemic [diseases Associated with Pattern Dystrophy.............................................................................. 268
Myotonic Dystrophy............................................................................................................................... 268
KjellLn's Syndrome (I lereditary Spastic I^ ta p ltg ia ).................................................................................270
Macular Palleriii Dystrophy in MJDD, MLI.AS, and M ER R F......................................................................272
Starga rdf's Disease (Hindus Havimaculatus)............................................................................................27S
Autosomal-Ltomin ant Central Areolar Chorioretinal Dystrophy LFnassociated with Edrusen or Flecks. . .286
Basal Laminar Drusen Associated with Type П Membranoproliferative Glomerulonephritis.................... 290
MalaLLia l.evantinese (Dayne's ] Eoneycomb Macular Dystrophy]............................................................. 2У2
North Carolina Macular Dystrophy and other Hereditary Macular Staphylomata (C olo b om ata)............ 2У6
’ Jienign* Concentric Annular Macular Dystrophy................................................................................... 300
Juvenile Hereditary Disciform Macular Degeneration .............................................................................. 300
E^seudoindammatory Sorsby's E'undus Dystrophy (SI D ) ........................................................................ 304
helicoid Peripapillary Chorioretinal Dystrophy { vChoroidiLis Areata,A' Sveinsson's
Chorioretinal ALLophy).......................................................................................................................... 306
Cone Dystrophy (Cone Dysgenesis).......................................................................................................306
Nonprogressive Cone [dysgenesis............................................................................................................ 306
Congenital Achromatopsia.................................................................................................................... 306
Cone Monochromatism.......................................................................................................................... Э08
Progressive Cone D ystrop hy..................................................................................................................308
E.ate-Onset Sporadic Cone [dystrophy.....................................................................................................310
Fenestrated Sheen Macular Dystrophy.................................................................................................... 312
Dominantly Inherited Muller Cell Sheen [dystrophy (Familial Internal Limiting Membrane Retinal
Dystrophy)............................................................................................................................................. 312
Asteroid Маги Iar D ystrop hy..................................................................................................................314
S[ogren-l.arsson Syndrom e.................................................................................................................... 314
Ai cardi's Synd ro m e ............................................................................................................................... 316
Alport's D isease..................................................................................................................................... 316
Retinal Exstrophy in Duchenne and Becker Muscular D ystro p h y...........................................................31S
Occult Macular D ystrop hy.................................................................................................................... 3tB
Unclassified Macular D ystrophies......................................................................................................... 320
Flecked Retina Associated with Cafe-Au-l.aiL Spots, Microcephaly, Lpilepsy- Short Stature, and
Ring 17 Chromosome.............................................................................................................................320
Benign E'amilial Fleck R e tin a ..................................................................................................................320
Congenital Slationaiy Night-Blinding Diseases...................................................................................... 322
Autosomal-Dominant Congenital Statiotiary Night Eilandness................................................................ 322
Autosomal-Recessive and Simplex CongeniLal Stationary Night Blindness................................................ 322
X-U nked Co ngen itaE S tatio nary N ight Ell i ndn ess....................................................................................323
Oguchi's Disease..................................................................................................................................... 324
Nonprogtessive Albipunctale Dystrophy [E:undus Albipunctatus}........................................................... 324
Kandorl's Flecked lle L in a .................................... L .... „ ................ 328
Retinitis Pigmentosa (Rod-Cone D ystrophies]...................................................................................... 328
t3sher Syndrome..................................................................................................................................... 336
'lypical Pigmentary Retinal Dystrophy with CoaLs' Syn d ro m e................................................................ 333
Atypical forms of Retinilis Pigmentosa.................................................................................................... 338
Leigh Syndrome (NARP Syn d ro m e}.......................................................................................................338
Retinitis Pigmentosa Sine Pigmenti......................................................................................................... 340
Preserved Para-arterial RPli in Retinitis Pigmentosa.................................................................................340
Retinitis Punctala Albescens [R P A }...................... . , .........................................„ ............................342
Bothnia D ystro p h y............................................................................................................................... 342
Newfoundland Rod-Cone Dystrophy.......................................................................................................344
BJettjrs Crystalline Tapetoretinal D ystrophy............................................................................................346
Leber's Congeni LaI Am au l o s e s ...............................................................................................................330
Neonatal Retinal Dysgenesis and Dystrophies Associated with Systemic Diseases..................................... 332
Stationary or Slowly Progressive Dominantly Inherited TapetorelinaJ Dystrophy.................................352
E.ate-Onset Retinal Macular Degeneration...............................................................................................354
Eixtensive Macular AtLophy with Pseudodrusen Like AppeaLance............................................................. 356
West Endies Crinkled Relina I Pigment BpiLheliopathy.............................................................................. 358

Figures with indicate bonus stereoscopic images available online a I wwvv.eiipertconsult.com

£]ho roidenem la...................................................................................................................................... 360
Cone-Rod Dystrophies [Inverse Pfe^ prit^Ty Retina] Dystrophy)............................................................ 366
Gold man n-E'avre Syndrome (linhanced S-Cone Syndrome.................................................................... 368
X-Linked Juvenile lletlnoschisis............................................................................................................. 370
Non X-Llnked boveal Ret Inosch Isis........................................................................................................ 374
Localized oi tegmental. lrorms of ReLinllls Pigm entosa..........................................................................374
Autosomal-Dominant Vitreoretinochoroldopalhy............................................................................... 374
In te rio r AnnuIar (L’ericentraL Circinan?. PeripapiElary) f’igmenlary Kelinal D ystrop hy........................ 376
Paravenous Retlnochoroidal Atrophy..................................................................................................... 376
Sector pigmentary Relinal Dystrophy..................................................................................................... 376
Unilateral Ret ini Lis Pigmentosa................... , . . ..................................................................... ь b .378
Atypical Pigmentary Retinal Dystrophies Associated With Melaboftc And Neurologic Disorders............. 380
Gyrale Atrophy of the C h oroid............................................................................................................. 380
Hooft's Syndrom e.................................................................................................................................382
C ystln o sis............................................................................................................................................382
Albinism .............................................................................................................................................. 384
Pfiliiaiy Hereditary I lyperoKaturia........................................................................................................ 386
Inborn Error о Г Vitamin В3j Metabolism................................................................................................386
Methylmalonic Acad Urea Cobalam in-CType....................................................................................... 388
Vila m In A and li Deficiency................................................................................................................... 388
Jletinal C illopalhies.............................................................................................................................. 388
Uardel-ftledl Syndrom e........................................................................................................................ 390
Laurence-Moon Syndrom e................................................................................................................... 390
Alslrom Syndrome.................................................................................................................................390
Juvenile Familial Nephrophthisis Associated with Japetoretlnai LVgeDeration
( Senio r- Loken Synd ro me} ................................................................................................................... 390
Jeune Syndrom e................................................................................................................................... 392
Arleriohepalic DyspEasia [Alagilie's Syndrom e).....................................................................................342
Incontinentia Pigmenti Achrom lans..................................................................................................... 392
J-EeimLeKs Syndrome.............................................................................................................................. ЗУ 4
Cockayne's Syndrome........................................................................................................................... 396
Hereditary Microcephaly and Retinal E)egeneration............................................................................... 396
Osteopetrosis and Chorioretinal Degeneration.....................................................................................396
l^erioxisomal Diseases........................................................................................................................... 396
Cerebrohepatorenal Syndrome [XeIIweger's Syn d ro m e)....................................................................... 397
Ad reno leukodystrophies......................................................................................................................397
Jtefsum's Syndrome [I leredopathia Atactica roiyneuriliTorm tsJ............................................................ 398
Cenebro-oculohepaLorenal Syndrome (Arena's Syndrom e).................................................................... 398
Chorioretinopathy and Pituilary Dysfunction....................................................................................... 398
Retlnilis Pigmentosa and Autoimmune Polyendocrinopalhy..................................................................398
Atypical 'Iapetoretlnal Dystrophy Associated With Olivopontocerebellar Atrophy Konigsmark
Type ID , Jlardtng'lVpe 1 1 ................................................................................................................... 400
Spinocerebellar Ataxia 7 ........................................................................................................................ 400
Pantothenate Kinase-Associated NeurodegeneraLion [Hallervorden-Spatz Syndrom e)................ .. . . .402
Mitochondrial tincephalomyopalhies.................................................................................................. 402
Kearns-Sayre Syndrome........................................................................................................................ 404
Danon Disease...................................................................................................................................... 406
Bassen-Kornzweig Syndrome................................................................................................................ 406
fam ilial ] lypohetallpoproteinemia........................................................................................................ 408
tieu го Iip idoses...................................................................................................................................... 408
Sphingollpidoses.................................................................................................................................410
Gangliosidosis...................................................................................................................................... 410
Tay-Sachs Disease.................................................................................................................................410
SandhoiTs Disease.................................................................................................................................410
N lema nn- Pick D Isease........................................................................................................................ 412
Landing's Disease (Generalised CM: Gangliosidosis, type I ) ..................................................................414
barber's Disease ( Dl&seminaled E.ipogranulomatosis].............................................................................414
 Metachro malic Leukodyst ro p h y ............................................................................................................414
С aucher's Disease..................................................................................................................................414
Mucopolysaccharidoses......................................................................................................................... 415
Mucolipidoses....................................................................................................................................... 415
С aIactosia 1idosis ( Goldberg- Coll Ler Sy nd ro me} ................................................................................... 416
Neuronal Ceroid Lipofuscinoses............................................................................................................418
E.ong-Chain ^-Hydroxyl-Acyl-Coenzyme A Dehydrogenase (I.C HAD) deficiency.................................... 420
References............................................................................................................................................. 421

6 Macular Dysfunction Caused by Retinal Vascular Diseases 437

Am hi Дфяrival

Retinal Vascular Anom alies....................................................................................................................438

13ereditaiy Keti па I Artery 'i o rtu o sity...................................................................................................... 438
Inherited Retinal Venous H ead ing......................................................................................................... 438
Retinal Venous 'lortuoslly in In fa n ts...................................................................................................... 438
Congen ital FrepapJ Ila ry Vascul ar l.o o p s................................................................................................ 440
Congenital Retina] Macrovessels and Arterlovenous (Communications.....................................................442
Anomalous EoveaI Avascular / o n e .........................................................................................................448
Obstructive Retinal Arterial [diseases...................................................................................................... 450
Ei mho] ic О bs tru ctlo n ............................................................................................................................ 450
Endogenous Embolization from the Major Arteries and J leart................................................................450
Atheromatous Retinal Anerial E-mbol nation following Use of Onyx to Embolize Internal
Carotid Aneuiy&m..................................................................................................................................460
Alii aI Myxoma....................................................................................................................................... 462
t-'at EimbollKaLion..................................................................................................................................462
Eimbolization Claused by Intravascular Aggregation of Blood Elem en ts..................................................462
Disseminated ] ntravascu Iar Coagulopathy..............................................................................................462
Trolein 5 Deficiency...............................................................................................................................462
l.eukoembolization (RurLscher's and PurEscher's-l.ike lietlno p athyj....................................................... 464
Erythrocytic Aggregation.......................................................................................................................466
Exogenous Em bolization.......................................................................................................................468
'la k Retinopathy.................................................................................................................................... 46S
Retinal Emboli Erom Artificial Cardiac Valves.........................................................................................470
Retinal Anerial limbo!ization hallowing Corlicosteroid Suspension Injection.........................................^470
Obliterative Retinal Arterial Diseases...................................................................................................... 472
Arteriosclerosis and Atherosclerosis...................................................................................................... 472
Unusual Causes of Retinal Artery and Arteriolar Thrombosis.................................................................. 472
Arteritis and Arteriolitis......................................................................................................................... 472
Edlopathic Recurrent Branch Retinal Arterial Occlusion {Su&ac Syn d ro m e}............................................ 474
X-]lay Irradiation.................................................................................................................................... 47S
Retinal Arterial Obstruction Caused by Spasm........................................................................................ 480
Retinal Migraine . . , ............................................ L ........................................................................480
Retinal Arterial Obstruction Caused by Diseases of Surrounding Structures............................................ 480
Retinal Arterial hypoperfusion Caused by Systemic Hypotension and Ocular Hypertension.................... 482
Retinal Arterial Hypoperfusion Caused by Carotid and Ophthalmic Artery Obstruction......................... 482
Takayasu Retinopathy............................................................................................................................ 484
t-'ibromuscular D ysplasia.......................................................................................................................436
Retinal Hypoperfusion Caused by Cardiac A n o m alie s.......................................................................... 486
Retinal Arterial Hypoperfusion Caused by Occlusion of Retinal Venous O utflow .................................... 486
Retinal Arteriolar Obstruction Claused by Systemic Hypertension and Collagen Vascular Disease............488
Acquired Retinal Arterial Macroaneurysms..............................................................................................494
Retinal Capillary Diseases...................................................................................................................... 500
Cystoid Macular Edema After Cataract Extraction.................................................................................. 500
Cystoid Macular Edema Associated with RhegmalogenousRetinal D etachm ent..................................... 504
Cystoj d M acu lar Ede ma Eol Io^vi ng Other'] у pes о f I ntraocu! ar Su rg e ry................................................. 50 4
Co nip] icatio ns ¥oi Iowi ng Cystoi d M acula г E d e m a ................................................................................ 506
InfantiEe Cystoid M aculopatby.............................................................................................................. 506
Cystoid Macular hdema Associated With Choroidal Melanomas ...............................>■.................. .506
Cystoid Manila г Ldema and'I cpical Hpinephrine and EVostaglandin Inhibitor Therapy..........................506
Cystoid Macular iidema Associated vviLh Ocular inflammatory Diseases.................................................. 506
Cystoid Macular Hdema From О the г Causes........................................................................................... 50S
Idiopathic Cystoid Macular lidema......................................................................................................... 50Й
Pseudocysloid Macular hdem a.............................................................................................................. 50&
N icoti nic Acid M aculopa t h y .................................................................................................................. 510
Dominantly Inherited Cystoid Macular Ed e m a...................................................................................... 510
Primary or Congenital Retinal Telangiectasis (Lebeds Mlliaiy.Aneurysms, Coats'1Syndrome] . . . . . . .514
facioscapulohumeral Muscular Dystrophy and Coats' Syn dro m e.......................................................... 520
Congenital and Acquired idiopathic Macular Retinal Telangiectasia........................................................522
Group ] A: Unilateral Сjo ngen ilaf Macular 'let angiectasi a ........................................................................ 522
Group ] B: Uni lateral ldiopathicr hocal Macular 'I'elangiectasis................................................................52 A
Croup 2A: tiilateral. Idiopathic.. Acquired Macular (Jujitafoveolar) Telangiectasia.....................................526
Croup 2E5: |uvenite Occult FaEnilial IdiopaLhic JuxlafoveoEar Retinal Telangiectasis..................................532
Group ЗА: Occlusive idiopathic JuKlafovealar RelinaE Telangiectasis........................................................ 532
Group 3B: Occlusive Idiopathic luxtafoveolar Retinal Telangiectasis Associated with Central
Nervous System Vasculo pa t h y .............................................................................................................. 534
Cerebroreli пaI Voscu lo p a lh y ................................................................................................................. 534
t Eeredi tary I lemorrh agic 'I el angieclas ia ( Jfrn du- Os ler—WeberD isease)................................................... 534
Idiopathic Etetinal Vasculitis, Aneurysms, and Neuroretinopathy: {IR V A N )............................................ 538
Diabetic EJetinopathy............................................................................................................................ 540
Nonretinal Ocular Changes in Diabetes.................................................................................................550
Diabeles Mellitus, Diabetes insipidus. Optic Atrophy and Deafness (D1DMOAD,
Wolfram Syndrome]............................................................................................................................... 553
lladiation Retinopathy.............................................................................................................................554
Sickle-Cell Retinopathy......................................................................................................................... 556
Primary Retinal Vasculitis or Vasculopalhy (lijles' Disease]......................................................................564
Retinopathy of Prem aturity.................................................................................................................... 570
fam ilial Lxudative Vitreoretinopalhy...................................................................................................... 576
Incontinentia Pigment i ......................................................................................................................... 573
Dystroglycanopathies [Muscle-tiye-Hrain Disease).................................................................................5£2
Dyskeratosis Congenita......................................................................................................................... 5S4
Retinal Venous Obstructive Diseases...................................................................................................... 5£6
Centra] Retina] Venous O bstruction...................................................................................................... 5Si3
Impending. Incipientr E1arliatf or incomplete CenLral Retinal Vein Obstruction....................................... 5flS
Nonischemic Central Retinal Vein Obstruction (Perfused Central Retinal Vein Occlusion)....................... 5ЙЙ
Severe (ischemic) Central Retinal Vein Obstruction (Nonperfused Central RtrlinaL Vein Occlusion). . . ,5&&
Branch Retinal Vein Obstruction............................................................................................................596
] Eemiretina] Vein Occlusion.................................................................................................................... 602
lietinal Vascular Changes Caused by Hematologic Disorders...................................................................604
Retinopathy Associated with Anemia...................................................................................................... 604
Retinopathy Associated with Hyperviscosity........................................................................................... 60Й
Ret inopathv Associ ated w ilh I iy peri ipoprotei nemi a .............................................................................. 610
References............................................................................................................................................. 612

M a c u la r D y s fu n c tio n C a u s e d b y V it r e o u s a n d V i I re о re Lin a] In te rfa c e

A b n o r m a lit ie s 629
AufiLj A^tfJ U'rJj

Anatomic Considerations....................................................................................................................... 630

Vitreoschisis.......................................................................................................................................636
Vi treous' E'raction Macu Iopalhies.........................................................................................................63 S
Traction Maculopathy Claused by Incomplete ]\jslerior Vitreous D etachm ent.................................... 640
 Idiopathic Traction Maculopathy Lin associated wi ill I’exterior Vitreous tJetachment , . . .644
Idiopathic Aye-Related Macular H o le ............................................................................. .646
Macular Dysfunction Caused by Epiretinal Membrane Contraction................................. .672
Class ifi cation of Jipiretinal Membranes According to Severity of Retinal Distortion . . . . .672
Classification of lipiretinal Membranes According to Associated Biomicroscopic findings .674
]:o\reolar Hole in lipiretinai Meibbrane Simulating a Macular I LoLe (Pseudomacular Hole) .674
ILpsretinal Membrane Formation Associated with Full-'I hickness Macular Hole .676
Classification of Lpiretinal Membranes According to Associated Disorders . .67 S
Vi treopapi Ilary Tract! o n ............................................................... .636
Retinal Changes Associated with TCheginatogenous Retinal Detachment .686
Degenerative Ret inosch isis .694
Am yloidosis................... .702
Asteroid H ya lo sia........... .704
Vitreous C y sts................ .7Q6
References...................... .70S

8 Traumatic Retinopathy 713

Attita Л^тпш/

Eteriin's Eidema (Commotio Retinae}................................... .714

Posterior Choroidal Rupture [Traumatic Choroidopathy) . . . .716
Macular Complications of E’eripheral Chorioretinal Contusion and RupLure (Sclopetariia) .720
Postlraum aLie Macular Hole and t-'oveo Iar Pil . . „ „ b „ . ................................. .722
Purlscher^s Retinopathy..................................................................................... .722
Terson'i Syndrome............................................................................................. .724
Hemorrhagic Maculopathy Caused by Subarachnoid and Epidural Injections. . . .726
ENjstcontusion Neuroretinopathy....................................................................... .726
Shaken-llaby Syndrom e..................................................................................... .72 &
Retinal Vessel Rupture Associated with Physical Lxertion (Valsalva Retinopathy) . .730
Evulsion of the Optic D is c ................................................................................ .732
Ocular Decompression Retinopathy.................................................................. .732
intraocular toreign B o d ie s ................................................................................ .734
Chorioretinopathy and Optic Neuropathy Associated with Retrobulbar Injections .736
Photic Maculopathy........................................................................................... .738
Solar Retinopathy.................................................................. .73 S
Welding-Arc Maculopathy....................................................... .742
Lightning and Kleclromtion Retinopathy.............................. .744
Acute ЙЩоЫ Damage Caused by Ophthalmic [nst rumen is. . . .746
Retinal Injury from l.aser Exposure......................................... .746
References............................................................................. .750

irrricj
 CONTENTS
V O LU M E T W O

Toxic Diseases Affecting Lhe Pigment LpitheNum and ReLina 755

Anita A^rrm'tfJ

Chloroquine (Araten) and Hydroxychloroquine [PlaquenilJ Retinopathy................................................756

'Ihioridazine [M ellaril) Retinopathy....................................................................................................... 762
Ch Ioipro marine (ihorazine) Retinopathy............................................................................................... 764
Clofazimine Retinopathy........................................................................................................................764
Defcryxamtup M aculop ath y..................................................................................................................766
Siderotic Retinopathy............................................................................................................................. 76Я
Chalcosis M aculopathy.......................................................................................................................... 770
ArgyrOSES................................................................................................................................................ 770
CispEatinum im dBCN IJ [Canuustine) Retinopathy................................................................................. 772
Tamoxifen Retinopathy.......................................................................................................................... 774
O x alosis................................................................................................................................................ 774
Canthaxanthine M aculop ath y............................................................................................................... 776
West African Crystalline M aculopathy.................................................................................................... 77Я
Nitrofurantoin Crystalline Retinopathy........... ...................................................................................... 77Й
Necked Retina .Associated with Vitamin A Deficiency.............................................................................. 7S0
Aminoglycoside M aculopathy................... .. . . .............................. ..................... ...........................7S2
Interferon-Associated Retinopathy..........................................................................................................7S4
Methamphetamine and Cocaine Retinopathy......................................................................................... 7S6
presumed Dextroamphetamine M aculopathy......................................................................................... 7S6
Li docaine-Epinephrine Toxicity.............................................................................................................7Й6
Qui nine' toxicity..................................................................................................................................... 7fl Й
Methyl Alcohol Toxicity.......................................................................................................................... 790
Bisphosph оnates..................................................................................................................................... 750
Pact ilaxelToxi c it y .................................................................................................................................. 790
Im.uinib Mesylate {Gleevec} Toxicity....................................................................................................... 792
Clitazone'lbxicily.................................................................................................................................. 792
N icoti nic Arid Maculopa t h y .................................................................................................................. 792
Epinephrine and Prostaglandin An alog-induced Cystoid Macular Edem a................................................ 792
Venlafaxine............................................................................................................................................. 732
Marathon/Dehydration Retinopathy....................................................................................................... 794
High-Altitude Retinopathy.....................................................................................................................794
Carbon Monoxide iietinopalhy............................................................................................................... 794
Indocyanine Creen Toxicity.................................................................................................................... 796
'Tacrolimus T o x icity................................................................................................................................796
Amiodarone Optic Neuropathy............................................................................................................... 796
Sildenafil (V iag ra).................................................................................................................................. 796
Corticosteroid-Associated Central Serous Chorioretinopathy................................................................... 796
Retinoids................................................................................................................................................ 79S
Cidofovir................................................................................................................................................79 Й
Rifabutin................................................................................................................................................ 79 S
Vigabatrin............................................................................................................................................. 79 Й
]ndometbacin Retinopathy..................................................................................................................... 79a
Digitalis and Digoxin Retinal T o x icity.................................................................................................... 79Й
Glycine Retina] Toxicity Associated with Transurethral Resect ion.............................................................. 79 S
H ud ara bine' i'oxicitv................................................................................................................................ 799
 Qljjfrwb X EI ]

Gemcilabine []urtscher-Like RelinopaLby................................................................................................ 799

Acute MicuJaK Neuroreti пора thy after Injection ofSym palhom im etics..................................................799
Drug-Induced Acule M y o p ia ................................................................................................................. 799
References.............................................................................................................................................SO О

10 Infectious Diseases of the Retina and Choroid 805

Anita А $ т ш 1

[\ogenic Cho rlo ret] nit i s .......................................................................................................................Я06

Focal indolent Metastatic Bacterial Retinitis in Acquired Immune Deficiency Syndrome {A ID S ).............. SOS
Bacteria] Choroidal Abscess....................................................................................................................SOS
Nocard ia ................................................................................................................................................810
Cat-Scratch D isease............................................................................................................................... S I2
Lyme ttorretiosis.................................................................................................................................... 816
Leptospirosis.......................................................................................................................................... SI 6
l.uetic Chorioretinit is ............................................................................................................................ S IS
'I’uberculosis..........................................................................................................................................830
Lalesr D isease ....................................................................................................................................... 836
Leprosy.................................................................................................................................................. S3S
fungal Retinochoroiditis.......................................................................................................................Я38
Candida Retinochoroiditis....................................................................................................................840
Aspergillus Retinitis...............................................................................................................................842
Cocci dioidomycosis...............................................................................................................................842
Cryptococcosis......................................... ............................................................................................. 842
Mucormycosis....................................................................................................................................... Я44
Blastomycosis....................................................................................................................................... 846
Histoplasmosis Retinitis and Choroiditis in Immune Incompetent Patients............................................ 846
"Ibxoplasmosis Retinitis......................................................................................................................... 848
M alaria.................................................................................................................................................. 856
E^eumocystis Jiroveci C h o ro id itis.........................................................................................................858
'loxocariasis..........................................................................................................................................860
Cyslicercosis............................................ ............................................................................................. 862
Diffuse Unilateral Subacute Neurorelmitis..............................................................................................Я64
Filariasis and Guinea Worm ....................................................................................................................872
О nchocerciasis....................................................................................................................................... S7 2
E.oaiasis.................................................................................................................................................. 876
Diroftlariasis..........................................................................................................................................S76
Brugia Mai ay i and Wucbereria BaiicroftE................................................................................................ 876
Cnatbostomiasis.................................................................................................................................... Я78
Other Nematode Infections of the bye................................................................................................... S78
AngiostrongyEiasts..................................................................................................................................Я78
O phthalm om yiasis...............................................................................................................................880
C allip h o rid ae....................................................................................................................................... 880
Ophthalmomyiasis J nteina....................................................................................................................SSO
Gedoelstia Cristata..................................................................................................................................884
Lch enococcosis....................................................................................................................................... 884
intraocular I'remaloda............................................................................................................................ 884
Schistosom iasis.................................................................................................................................... 886
Fasciola Пера ties [Liver flu k e ).............................................................................................................. Я86
' I'rem aLodes in South In d ia ....................................................................................................................888
Retinopathy Associated with Rickettsial Diseases................................................................................... 888
Rickettsia Conorii (Mediterranean Spotted fever, M S F ).......................................................................... 890
Viral D iseases....................................................................................................................................... 890
Cytomegalovirus Retinochoroiditis and Optic N euritis.......................................................................... 390
Congenita] CMV In fe c tio n ....................................................................................................................890
Herpes Virus Retinorhoroidilis.............................................................................................................. 896
J Eerpes Si m ptex RetJ nocho roidi t i s .............................................. -896
] Eeipesvirus f t ............................................................................ .Й9Я
J Eerpes /osier C horoidopathy.................................................... .ау а
] Eerpes Zosteг Virus (H /V), Retinochoroiditisr and Optic .Neuritis . .a y s
Congenital Varicella Syndrom e.................................................... .ay a
Acute Retinal Necrosis {I Ecrpelic TEirombotic Retinochoroidal ArigiiLlis and Necrotizing Neuroretini tisj .300
Acute Eietinal .Necrosis in immune Incompetent Patients (Posterior Outer Retinal Necrosis] .90a
] ELiman Immunodeficiency V it u s [H iV ) and Acquired Immune Deficiency Syndrome . 912
tpstein-Barr Virus........................... .916
] Eli man 'J'-lymphotropic Virus Type I .У16
Rubella Retinitis........................... .913
Subacute Sclerosing PanencephaEitis .920
West \ile Virus Chorioretinitis .922
Dengue lever......................... .924
Chikungunya V ir u s .............. .92 a
Mumps Neuroretinitis........... .92 a
Elft Valley fewer Retinitis . . . .930
Vilritis and Retinitis in Whipple's EJisease .930
References . .................................... .. .934

Inflammatory Diseases of the Retina 947

Amta Aganual

Retinal Vasculitis and AeTlvasculEd*................................................................................ ,94 a

Acute Retttiyl Periphlebitis and Panuveilis Associated with Viral-Like Upper Respiratory D isease ,94 a
Idiopathic E-'rosted-Branch A ngiitis................................................................................ .950
Aeute Multifocal Hemorrhagic Retinal V a sru litis.......................................................... .930
Jietinocboroidal Degeneration Associated With Progressive Eris N e cro sis...................... .952
Acute Posterior Multifocal Placoid Pigment LpitheEiopathy............................................ .954
Persistent EMacoid Maculopathy..................................................................................... 960
Relentless Rlacoid Choroidopathy................................................................................ .962
Serpiginous Choroiditis [Geographic Choroiditis* l-Eelicoid PeFipapilEaiy Choroidopathy) .962
Acute Idiopathic M aculopathy.................................................................. ................... .У70
Unifocal 3telioid Choroiditis........................................................................................ .972
Acute Retinal Pigment Eipitheliitis................................................................................ .974
Mu hi pie Lvanescent While-Dot Syndrome..................................................................... .976
Acute /onal Occult Outer iietinopathy.......................................................................... ,9ao
Acu te Annu Iar Occu 11Outer Ret in o p a th y ..................................................................... .9S4
Disorders Simulating the Presumed Ocular ! tistopEasmosis Syndrome { pseudo-E:0 US J . ,9aa
MuEtifocaE Choroiditis and Panuveilis . . . ,9a a
Punctate 3nner Choroidopathy................... .990
.Acute Macular Neuroretinopathy................ .9У4
J Earada4 Disease......................................... ,9ya
JEarada4-L.ike Syndrome in Children........... 1002
Sympathetic U veitis................................... 1004
Acute tixud aLive E’olv morph ous Vi tel I ifonn Maculopathy. . . ю оа
Progress ive 3ubret inal ]-'ibrom atosis.................................... 1014
]\>sterior S c le ritis ............................................................... 1016
Choroidal Sarcoidosis....................................................... 1022
Retinal and Optic Nerve Sarcoidosis.................................... 1024
Acute Idiopathic Multifocal Inner itetinitis and NeuroreLinilis 102a
Ueh^el's Disease.................................................................. 1030
Diffuse, Chronic Non necrotizing Ret ini (is, Vilrilts, and Cystoid Macular Idem a 1034
Pars Rlanilis, E^ripheral Uveitis, or Chronic Cyclitis......................................... 1036
3di opath ic Age-re lated Vit ritis.......................................................................... ю за
Vltiliginous Chorioretinitis (birdshot Retinochoroidopathy)........................... ю за
 titan [jabs) Syndrome...........................................................................................................................1044
'I'ubuloinlerslitiaE Nephritis and Uveitis Syndrome ( U N IJJ.................................................................... 1044
Crohn's Disease . ................................................................................................................................ 1048
Collagen Vascular L^Eseases.................................................................................................................. Ю48
Eg4 N ephropathy................................................................................................................................ 1050
Systemic Lupus Erythematosus............................................................................................................. 1050
Chuig-Strauss Syndrom e..................................................................................................................... 1052
E'amiELai Chronic Granulomatous Disease of C hildhood.......................................................................1054
References........................................................................................................................................... 1056

12 T u m o rs o f th e R e lin a l P ig m e n t lip iL h e liu m ( R P E ) 1065

A\un /) Sitigji. Attfla

MeianoLic Nevi of the Retinal Pigment EpiLhelium .............................................................................. 1066

SoEi la ry-'I Vpe Congenital J [yperLrophy ofthe Retinal Pigment Epithelium [C H R P E ]............................. 1066
Multiple CEIRPE Associated with EamiEial Adenomatous Italy posis and Gardner's Syndrom e................ 1070
Grouped-'iype Congenital Pigmented Nevi of the Retinal Pigment Epithelium, "Bear'ftacfcs"..............1072
Albinoticand NonpLgmented Nevi of ihe Retinal Pigment Ep ith e liu m .............................................. 1074
Grouped-! ype Congenital A Ibinotic and Hypomelanotic Nevi of the Jtetinal Pigment EpiLhelium,
n]\>tar Hear tr a c k s '............................................................................................................................. 1074
Solltaiy-Туре iiypomeEanotic and Л1bimotic Nevi [Torpedo M acuEopathyj........................................... 1076
Congenital Simple Hamartoma of ihe Petinal Pigment Epithelium [Congenital i Eyperplasia of the
Retinal Pigment Epithelium, E’igmeлt Epithelial A d en o m a)................................................................. I07S
Combined Pigment Eipithelial and Retinal I lainartoma Involving the Optic Disc.................................1080
Combined Pigment Epithelial and Retinal Hamartoma Without Optic Disc Involvem ent................... 1082
Li ni lateral Retinat Pigment Epithelial Dysgenesis (Variant о Г Combined Elamartoma of the
Retinal Pigment Epithetium and Retina)............................................................................................... 1088
Reactive Hyperplasias of the Retinal Pigment Epithelium Simulating Hamartomas and Neoplasias , . , 1090
Adenocarcinoma (Malignant Epithelioma) ofthe Retinal Pigment Epithelium ......................................1094
References........................................................................................................................................... 1096

13 N e o p la s tic D is e a s e s o f th e K e L in a 10Э9
Arurt EJ .Striii^ Atiiln А ^ г г ^

Retinoblastom a................................................................................................................................... 1100

Reti noma/Ret in o ry to m a ......................................................................................................................1104
Medulloepithelioma.............................................................................................................................. Ш 2
Astrocytic J-i amarlo m as........................................................................................................................ 1112
Reactive Astrocytic Eiyperplasia Simulating an Astrocytic Ham artom a................................................... 1120
Retinal Vascular I lamartomas................................................................................................................1120
Retinal Cavernous Hem angiom as........................................................................................................1122
Retinal Capillary Hemangioma..................................................................................... ....................... 1128
Reti nal 'I el angiectas is and Arteriovenous Aneurysm...............................................................................1138
Vasoproitferalive Retinal Tumor ( Reactive Ketinal Vascular Proliferation).............................................. 1140
E.eukemic Rett no pa thy and Optic Neuropathy....................................................................................... 1142
V itreoretinal Lymphomas......................................................................................................................1150
Primary Central Nervous System Lymphoma (P C N S L )......................................................................... 1150
Mycosis Eungoidet................................................................................................................................ 1156
Eymphocytic Lym phom a......................................................................................................................1156
Other lymphomas and Related Conditions.......................................................................................... 1158
Adult Т-Cell Leukemia/lymphoma....................................................................................................... 1158
Richter Transform ation........................................................................................................................ 1160
AngioendotheliomaLosis..................................................................................................................... 1160
Mu Iliple Myeloma................................................................................................................................ 1162
E.ymphomatoid Granulom atosis.......................................................................................................... 1162
PosttransplanL [ymphoproliferative D isorder....................................................................................... 1162
Metastatic Carcinoma to the Retina and V itreous............................................................................... 1164
Paraneoplastic Retinopathy Associated with Carcinoma
(Cancer-Associated Retinopathy or CAR Syn d ro m e).......................................................................... 116Я
Me Ianoma-Associ aled Ret inopalhy (M AR Synd rome).......................................................................... 1170
Paraneoplastic Vitelliform Retinop athy............................................................................................. 1172
Reference*......................................................................................................................................... 1] 7J5

Neoplastic Diseases of the Choroid 1179

Arm? D Sjfi^/г,. Anila lAgarufal

Choroidal N e v i................................................................................................................................. 11SO

Melanocytoma....................................................................................................................................119Й
Diffuse Sclerochoroidal Melanocytic N evu s........................................................................................11DO
Diffuse Posterior Choroidosclera I Melanotic Schwannoma.................................................................. 1192
Multiple Choroidal Nevi and Melanoma Associated with Neurofibromatosis S....................................1192
Choroidal Malignant Melanoma,........................................................................................................ 1196
Bilateral Diffuse Uveal Melanocytic Proliferation Associated with Systemic C arcin o m a............... . .1202
Circumscribed Choroidal Hemangioma............................................................................................. 1206
Slurge-Weber Syndrojne................................................................................................................... 1212
Ipsilateral Facial and Diffuse Uv^nl Capillary Angioma Associated with Microphthalmos,
Heterochromia of the Iris, Chorioretinal Arterial Anastomosis, and tlyp o to ny................................... 1216
Choroidal Osteom a............................................................................................................................121Я
Sclerochoroidal Calcification............................................................................................................. 1224
Neuro fibrom a................................................................................................................................... 1226
Sch w ann om a................................................................................................................................... 122Я
Uveal Leiom yom a.............................................................................................................................. 122Я
Reactive Lymphoid Hyperplasia of the Llvea........................................................................................ 1230
Uveal Lym phom a.............................................................................................................................. 1234
Choroidal MetastaticTumors..............................................................................................................1236
Metaslatic Sarco m a........................................................................................................................... 1242
Leukemic Choroidopathy................................................................................................................... 1244
] Eisliocytosis [Frdheim-Chester D isease}.......................................................................................... 124Я
References..................................................................................................... ...................................1250

Optic Nerve Diseases that may Masquerade as Macular Diseases 1255

Anita Aganti$t

Oplic Disc Anomalies Associated with Serous Detach ment of the M acula............................................1256
Congenital Til of ihe Optic Disc and Serous Dclachment of the Macula.............................................. 1256
.Acquired Pits of the Optic N e rv e ........................................................................................................ 1260
Coloboma, ]mftapapi 11ary Staphyloma, and Morning С loiy D eform ity.............................................. 1262
Papillorenal (Renal Colohoma) Syn d ro m e ........................................................................................1264
Optic Disc Hypoplasia and'lilted-Disc Syndrome............................................................................... 1266
Dm sen [Hyaline Bodies) of the Oplic Nerve H e a d ............................................................................. 126Я
Hereditary Optic Neuropathies...........................................................................................................1272
Dominant Optic Atrophy [Kjer'l у p e ) ................................................................................................1272
Leber's Hereditary Oplic Neuropathy...................................................................................................1274
Leber's Idiopathic Stellate Neuroreti nit is and Multifocal R e tin itis.......................................................127Я
Recurrent Optic Neuropathy Associaled W ith Family History of CharcoL-Marie- ['oolh Disease...........12Я2
Familial Dysautonomia......................................................................................................................12Я2
Neuroretinopathy and Progressive Facial i-Lemialropby....................................................................... 12Я4
Anlerior Ischemic Optic Neuropathy................................................................................................... 12Я4
Idiopathic (Nonarteritic) Anlerior Ischemic Optic Neuropathy............................................................ 12Я6
Idiopathic Anlerior Ischemic Optic Neuropathy in the Young (AEO N V).............................................. 12ЯЯ
Arte rilic An le rio r I schem ic Op tic Neuropathy { a-Al O N ) .................................................................... 12ЯЯ
Idiopathic Optic Neuritis and P a p illilis ............................................................................................. 1290
Optic Neuritis in C h ild re n ................................................................................................................ ] 292
Traumatic Optic Neuropathy..............................................................................................................1292
Rad ialion-Induced Optic N europathy................................................................................................ 1292
Optic Nerve M eningiom as................................................................................................................. 1292
Optic Nerve t'.] to m a s ...........................................................................................................................1294
Visual 1joss Secondary to Papilledema Caused byincreasedintracranial Pressure.................................. 1296
E’seudolumor Cerebri (Idiopathic EntracranialH ypertension)..............................................................1296
Nutritional AmbEyopia [Toxic/Nutritional OpticNeuropathy)..............................................................1296
Diabetic Pa pi] topathy.........................................................................................................................1297
References......................................................................................................................................... 1297

Jnrfai
This page mtentlonaSly left blank

t lrst, ! want to express my thanks It) my chairman,
Dr. Paul Sternberg. fur his confidence in allowing me lo
work on the 5L|1 edition of the Class AtIль. His counsel,
support, and periodic overseeing helped keep the project
in tine and on to conclusion. 'Hie strength of any work
is its contents. Towards this end, [ am indebled to Dr.
Aruii D. Singh for his latent and time in updating the
tumor section of ihe boob. J am also deeply grateful to
all my colleagues and friends, who haw unhesitatingly
shared their patients' case histories and images. Jheir
generous contributions have enhanced immeasurably
the content and quality of the Allas. Ihe Allas helped
me make several new friends around the world; to my
immense surprise and pleasure, not one retinal special­
ist declined to con tribute cases wfien I approached ihem,
oflen as a complete stranger. I am particularly grateful lo
Dr. Amod tlupta, <chairman of Ophthalmology at my
ninui muter, PGl, Chandigarh and Dr. Vishali Gupta for
the images and cases (hey contributed, and the knowl­
edge they shared that made the Atlas truly international.
My colleagues at Vanderbilt gave me a free hand to select
any of their cases; ! sincerely respect their confidence. ]
also wish to thank my vitreoretinal colleagues for tak­
ing on some additional clinical responsibilities while
I devoted lime Lo this project. I feel fortunate Lo have
developed а close friendship with several leading reti­
nal specialisls who have welcomed me into Lheir com­
munity thus enhancing and enriching my knowledge.
Dr. Lee Jampol's review of some of the chapters was
timely and encouraging. Overali, the information in this
book originates not on Iу from my clinical experience
Acknowledgements
and publications of experts, buL also knowledge gained
through my long association with faculty, fellows and
residents at Vanderbilt and other institutions.
[ am deeply indebted to the always-positive Russell
Gabbedy, commissioning editor for lilsevier, and the
prompt and ever available Sharon Nash, developmenl
editor. 'Iliey both were the backbones of the produc­
tion of ihe Atlas. [ acknowledge Gillian Kichards, the
illustration manager, and Martin Woodward, the tal­
ented illustrator who has skillfully converted all of Don
Gass'1 hand drawn cartoons into illustrations. Stewart
Ljrking designed the elegant cover and pages and Kristen
Lowson was the editorial assistant. Nathan Wiles was
the multimedia producer. I thank Jess Thompson and
Andrew KiEey the project managers who coordinated the
various arms of production, even across continents and
smoothed and polished the final product. 1 thank stu­
dents Jose Garcia, rage Munn and Patrick Donahue for
their help in downloading loads of articles and PDFs
and painstakingly extracting images from presentations
and labeling them. 3 acknowledge the talented photog­
raphers at Vanderbilt for their abilities and lheir help
in enbanting the quality of images. In addition, this
Atlas would not be in its present form without the ever-
dependable t.ynne Siesser, my administrative assistant
who can find a solution to almost any problem.
Finally, 1 want to again thank the inspiration for this
project. Dr. |. Donald M. Gass. It has been a privilege
and honor to continue the work of my mentor, col­
league. and friend.
AfEi'ta Aganwl
Contributors
Arun D Singh M D
P ro fe sso r o f O p h th a lm o lo g y
D ire cto r, D e p a rt m e n l o f O p h th a lm ic O n c o lo g y
C o le Eye EnslitLttc
C le v e la n d C lin ic
C le v e la n d , O il, U S A
Forewords
This fifth edition of the Gass Allas of Macular Diseases
by Dr. Anita Agarwal brilliantly combines the best of the
previous editions with new technical advances, new enti­
tles and international perspective, '[he Atlas is a guide lo
help ihe clinician to arrive al a diagnosis of both com­
mon and uncommon diseases and to understand ihe
pathogenesis. The online version continues the tradition
for viewing slereo photographs. A hallmark of Dr. Gass'
teaching style is a simple yet detailed description of clini­
cal observations. 'lbis technique is preserved in the current
edition and enhanced through electronic illustrations and
Optical Coherence tomography (OCT) which frequently
depicts precisely whal Dr. Gass envisaged.
The table of contents is reorganized to reflect the explo­
sion of information, particularly in areas such as inflam­
matory and infectious diseases and tumors addressed in
separate chapters. Updates on manifestations of tubercu­
losis and syphilis are included along with new viral dis­
eases such as Eipstein-Вагт and West Nile virus. Chapter
11 contains a description of some new diagnostic entities
including acute idiopathic maculopathy and persistent
and relenLless placoid pigment epilheliopalhy. Tumors are
presented in three chap ten; - Retinal Pigment Kpithelium
( 12), Reti na { 13) and Choroid (] 4).
Dr. Agarwal and her co-author Dr. Arun D Singh,
have updated and extended the extraordinary work of Dr.
|. Donald M. Gass, an individual recognized as one ofthe
outstanding ophthalmologists of Lhe iOlh century and
helped to catapult his work into the future. In a time of
increasing paperless communication this wonderful text
will serve all physicians interested in macular disease as a
continuing reference to Improve their diagntrslic acumen
and provide better care for their patients.
John G. Clarbott, M D
Prt\feiiitrf Chair ami Dean Emeritus
tiascem Aifmerfite; J;uri;w!e. Mitimi, M
Whal a (ask it would be to rewrite the Bible! What about
the llible of retinal disease - ]Donald Cass' stereoscopic
atlas? Гог the last three decades this book has infonned us,
helped us in the diagnosis and treatment of difficult cases,
and sen-ed as the foundation for the evolution of the entire
field of medical retina. lhe brilliant pattern recognition,
memory, and synthesizing skills of Donald Cass allowed
him lo dtjcuinent an unimaginable amount of important
information in his book. He described for the first time
scores of neiv diseases and physical findings. Elis photo­
graphic collection - built over years of seeing patients
providing mail consultations, and attending innumerable
meetings, is unparalleled. ] (is knowledge of ocular patho­
logy added lo I be value of these archives, tven today. Lime
arid time again, when we suspect we have a new observa­
tion, perusal of the atlas shows us to be way behind Don.
As expected, Lhe Atlas aged and illness prevented Don
from completing a new edition. Jn most circuni stances
an edilor or many editors (hut not a single author)
would tty lo live up to the original and usually not suc­
ceed. tortunately one of Don's most talented disciples has
stepped into the breach.
Anita Agarwal was a fellow with Don and worked side
by side with him at Vanderbilt Univeisity. Since his death,
at conferences and in her publications, she has shown
immense grasp of Lion's knowledge base and hits taken
his place in educating us about the diseases that Don had
mastered. She has an excellent knowledge of systemic dis­
eases, genetics and many aspects of internal medicine
very rare in ophthalmology. Now we are grateful that she
has devoted years of her life lo updating this precious text.
Using Don's original files and her encyclopedic knowl­
edge of the retina, a new version of the Hihle appears.
(Dr. Arun D. Singh has assisted her on the chapters on
tumors.) The figures, including colour photographs, ОС Is,
angiographies, X-rays, and histopathologic specimens are
still unparalleled; multiple images are often available ofthe
same entity, demonstrating the variability of these diseases.
Anita has also added an international favour to lbe book
with disnrssions of diseases rarely or not seen in the LESA.
lhe hook covers common diseases {e.g. age-related macular
degeneration) in detail, but also discusses very rare entities
(e.g. diJfuse unilateral subacule neunoretinitis).
Ihere are other great books and atlases of triedical ret­
ina but this hook remains the Bible, '['hank you Anita
tfse. M. fampol, M D
Louis fcinberg Professcr ami Chair ffmeritNJ
Ncrtfirwesteni LTfFJi-CTiJjy, СЛгслдо, 1L
 O f all my ophthalmology books, the Cass Allas of
Macular Diseases has been the most treasured, and most
dog-eared, possession. Si net- I first acquired my copy of the
second edition as a resident, I avidly awaited the publication
of the more recent version, then immediately purchased it
to replace my Worn copy of the previous edition. When Dr.
Cass became too ill to write a fifth edition, I made a personal
commitment lo ensure that the legacy of tliis impactful book
would not pass away as well. I bus. it is with great pride that
I write this foreword, celebrating the continuance of the Class
Atlas, acknowledging the importance of careful clinical exam­
ination in the diagnosis of retinal disease, and recognising
the "passing of the baton” to the next generation.
Most of the ophthalmic community links J. Donald M.
Cass Lo the Kascom Palmer Eye Institute. Dr. (lass was one
of the founding physicians there, and forever changed our
understanding of the macula, tie opened our eyes to the
complexity of macular diseases, by creating logical, well-
defined classifications, based on careful! v made clinical obser­
vations and a remarkable necollection of patients with similar
histories and examinations, lie passed on this knowledge to
a world of residents, fellows, and colleagues across the globe.
In fad, virtually every retina specialist considers himself or
herself lo be a student of Dr. Cass- even if they never had the
opportunity to meet him. I'ortLinate were those who trained
at BPEi] and had the privilege of seeing patients with him and
attending the weekly fluorescein conferences. IL is no coinci­
dence that Eiaseom Palmer became the breeding ground for
many of the future leaders of the retina community.
However, the rest of us still learned from him. E'or some, it
was attending lectures at conferences like the Annual Meeting
of the American Academy of Ophthalmology. Por others,
they had the good fortune to work beside him as part of
mullicenter collaborative trials. [ vividly remember my first
meeting as an investigator in the Macular Pholocoagulalion
Study in the 19S0s. As Lhe day concluded, they held a ses­
sion where the Reading Center shared cases that were more
difficult or confusing. Ihe various experts would put for­
ward their thoughts: however, die case was not settled until
Dr. Class weighed in. t-.ven in a room lilled with the ‘'giants''
in our field, Dr. Cass had the final mird.
Here at Vanderbilt, we feel privileged to share some of
the credit for the legacy of Dr. Cass'' impact on ophthalmo­
logy. While |. Donald M. Gass was born in Canada, he was
raised in Nashville, Tennessee when his father accepted a
job in the state department of public heahh. Ele alLended
Vanderbilt as an undergraduate and as a medical student,
winning the ]4>under's Medal as the top student En his
graduating class. Ite married his high school sweetheart,
-Margy Ann, and it was anticipated thaL they would return to
Nashville when he completed his training.
However, his reLunt to Nashville was delayed for over JO
years until 1995 when he retired from his long-time faculty
position as Professor of Ophthalmology at the University
of Miami, lortunalely, his retirement was short-1ived.
Dr. Denis О Day, the chair al Vanderbilt al that lime- was able
to convince Dr. Class lo join the facully here, lie returned to
clinical practice writing, and leaching. Dr. O'Day writes, "Ihe
image that will forever endure for me is the one I saw every
week. It is of a man silling, surrounded by colleagues, resi­
dents, sludenls, and fellows. All aie peering at photographs of
the retina and the conversation is animated: all are engaged.
As J walk by. I recognise our singular good fortune in having
such a true academician in our midst"
One of those individuals surrounding D r Gass is
Dr. Anita Agarwal. Drawn lo Vanderbilt for a medical ret­
ina fellowship lo learn under D r Cass. Anita developed
an almost photographic memory of the Cass Allas, and an
encyclopedic knowledge of the reLin a literature, ihe came Lo
evaluate a case in a brilliant С ass-1ike manner. Over Lime,
her interest in the diversity of retinal diseases and her ability
lo make challenging diagnoses led her to eam a position of
respect among the small community of similar experts.
It is highly appropriate that Dr. Anita Agarwal should
be authoring ihis fifth edition. As well as any retina spe­
cialist in the world, she knows the previous editions from
cover to cover She has had the good fortune lo have daily
access lo the Cass Archives: Dr. Cass' slides, palienl charts,
and personal notes that were becjuesled to the Vanderbilt
Eiye Institute upon his death, in fad, much of her writing
has been conducted in a faculty office devoted lo the Gass
material: a room in which Dr. Cass' while coal hangs on the
door and where the space is dominated by the large wooden
cabinet with sliding trays that Dr. Cass would use lo prepare
his lectures and his manuscripts.
Dr. Agarwal has spent the better part of two years pre­
paring this magnificent fifth ediLion. While she has
restructured the chapters, updated the material lo include
newer conditions and new testing modalities like OCU
and engaged her talented friend and colleague. Dr. Arun
D. Singh lo wrile lhe chapters on intraocular tumors this
new edition retains the formal of the previous editions.
Most importantly, site has retained "the voice'7 of Dr. Cass.
Ihe words may be new or Lhe condition may have been
described subsequent lo Dr. Gass's death, buL D r Cass still
speaks lo us in this new edition.
I am hopeful that the Gass Atlas will live on through
many future generarions. 'Ihe editors and publishers at
Eilsevier have done Lhe ophthalmic community a xvonderful
service by investing in Lhe creation of this fiflh edition. I am
grateful for their confidence in Dr. Agarwal, and cerlain that
Lhe readers will agree Lhal this is a worthy successor Lo Lhe
previous editions.
Рай Sternberg, Jr., M.D.
G. W. H ate l>rafessor am i Cfr^nr;
ytm d erb ilt Eye in s titu te i\i\sh viik T, T,\'
XX! I

World Map
Internationa! Cases Presented in the Fifth Edition

Diabetes and Deafness,

Canada: Cispla1?n to^iaty
Newfoundland rod
cone йеуег-егацЁоп
ч________ ___________

France:
MacuEar atrophy
with pseudodrusen

r Tunisia;
Rickettsia conorii
^ _ ___ ___ _

f ---------------- "’I
West Indies
(French Guyana);
West Indies crinkled
Retinal pigment
spilhefiopathy
 XXftJ

Sweden;
Eotfi rti-з dystrophy

Netherlands:
Autsomal recessive Bestraphinopathy.
Central areolar chonordaE dystrophy.
Maternally inherited Diabetes an.d Deafness

Thailand:
Angiostrongjliasis

SflUdj Arabia:
Rrft Vailey fever retinitis Singapore;
Dengue fever

India;
Mycobaclerium tuberculosis,
Namibia: Takayasu arteritis, Mucormycosis
Gedoelstia c^istata Sarcoidosis, Sympathetic
ophthalmia, Trematode uveitis,
Leprosy, Dirofjlara. Chifcungunya
reEinitis. Malaria. Leptospiras-s,
Tacrolimus microangiopathy.
Ghloroqmne retinopathy. Laser
macular Ourn
Preface to the Fifth Edition
One of the т о й fortunate turns in life landed me only idiopathic, degenerative and miscellaneous causes of
square in from o f], Donald M Gass, my idol from a dis­ serous and hemonbagic retinal detachment. Ihe contents
tance- whose work I had read, studied and admired since of Chapter 7, (hat included both infectious and inflam­
the beginning of my ophthalmology training in India. In matory retinal diseasesr have been split into two separate
1997, I entered my medical retina Fellowship, initiating an chapter*, one on infectious diseases (Chapter 10) and a
unending. rewarding lesson from this giant. As known to second on inflammatory diseases (Chapter 11). Chapter
the entire world of retinal physicians, Deni Class has had 5 addresses heredo-dystrophic conditions of the retina,
a truly profound impact on our understanding of retinal choroid and pigment epithelium; it includes several new
and macular diseases. Mis keen observation skills, pho­ disorders including Bothnia dystrophy, Newfoundland
tographic memory of oculaF features, and ability to inte­ rod cone degeneration, and pattern dystrophy associated
grate clinical findings with pathological changes led him with newly identified systemic diseases such as maier-
to describe several diseases For the first lime and help us nally inherited mitochondrial diseases and hereditary
understand the pathogenic mechanisms of many other spastic paraplegia. 'Ihe neoplastic diseases have been reor­
previously described conditions. l\vo of his singularly ganised into three separate chapters for choroid, retina
important qualities - meticulous attention to clinical and retinal pigment epithelium and include the various
details and analysis oF stereoscopic images of the retina - benign tumors and hamanomas. Jhe chapter on infec­
became the hallmark of his defining publication, his tious diseases (Chapter 10] includes previously discussed
'Stereoscopic Allas of Macular Diseases'1 . Ihe evolution of bacteria] followed by fungal, parasitic and viral diseases,
Lbe Atlas over its multiple editions has captured and illus­ i lowever, various new entities and new information on
trated ihe tremendous grow Lb our field has experienced tuberculosis, leplospirosis, parasites, and viruses such as
over the decades between the first and Fourth version. chikungunya, dengue, west nile and rift valley fever have
ll is ihe greatest privilege of my professional life tobeen added. Attempts to include diseases prevalent out­
be selected to edit this new 5:h edition oF Cass' Atlas side the United Stales has been made to aid in diagnosing
of Macular Diseases . in this publication, i have tried to rare and unusual diseases. Ihe hand drawn illustrations,
retain the "voice" of Dr. Cass, and continue his work, which were a hallmark fealure of Dr. Cass' understand­
presenting new disease entitles, consolidating known dis­ ing of disease pathology, have been skillfully converted to
eases, and discussing new concepts in the pathogenesis of electronic artwork, and fundus photographs are now pre­
existing conditions. sented in color.
This edition incorporates a number of structural Ihe Atlas has maintained the case descriptive format
modifications. of Gass' teaching method, encompassing history, clinical
3’irst, each chapter includes an expanded table oF con­ exam and follow up when available. Ihe online version
cents to Facilitate locating the individual conditions. 'Ihe features stereoscopic images that are notated by a 3D sign.
contents of the Allas in Chapters 3, 5, 7, IQ and 11 of the A stereo viewer accompanies the book.
4rh edition have been reorganised. Previously.- Chapter 3 Overall, ihe AlEas emphasises clinical Features, palho-
was quite exhaustive and lengthy, containing all disor­ genesisr information about genetics and its role in dis­
ders that caused a serous or hemorrhagic retinal detacEi- ease pathogenesis where known, differential diagnosis,
ment. be it tnllammalary [such as V K ll and sympathetic and limited information on treatment. Ltlensive elabo­
ophthalmia), infectious (such as Toxocara or certain ration on results of clinical trials, controversies on medi­
fungal diseases), neoplastic (such as choroidal tumors), cal management and surgeiy are not discussed; the Atlas
degenerative {such as age-related macular degeneration) is designed to be an exhaustive guide in arriving at Lhe
or inherited [such as Malauia levantinese and Sorsby's proper diagnosis of common and uncommon diseases
dystrophy}. The various infectious, inflammatory, neo­ and understanding their pathogenesis.
plastic and inherited disorders have been moved lo indi­
vidual chapters, wilh the current Chapter 3 discussing Ап\1й Долгий?

Ihe accessibility of the tissues of the inner eye Lo
close scrutiny by the physician is unequaled by any
other organ of the body J laving squired a knowl­
edge of ocular pathology and the skills of ophthal­
moscopy and biomicroscopy. the physician is able Lo
record his in vivo observations of the ocular fundus in
gross paLhologic terras with reasonable accuracy, '['his
becomes of particular importance in evaluating Lhe
palienL with loss of central vision resuming from alter­
ations in the structure of the macula, lhe physician
should attempt Lo determine as far as possible the ana­
tomic changes present, such as choroidal atrophy, cho­
roidal thickening, choroidal wrinkling, change in color
of the pigment epithelium, serous detachment of the
pigment epilheEium. serous detachment of the retinar
hemorrhagic detachment of the pigment epithelium
and retina, cysloid retinal edema, inlraretinal hemor­
rhage, loss of retinal transparency, relinai wrinkling,
and preretina I membrane. Ele should also attempt Lo
determine the locus of the primary disease process-
choroid, retina] pigment epithelium, retinal, or vitre­
ous. Only after making these determinations can the
physician evaluate the significance of the patient's ocu­
lar, medicaE, and family history in arriving at a diagno­
sis, prognosis, and course of therapy.
A variety of ancillary studies may he helpful in cer­
tain instances. The use of intravenous fiuorescein is of
particular value in detecting and defining certain physi­
ologic as well as anatomic changes in the ocular fundus.
'lhe purpose of this atlas is to utilize black and white
fundus photographs, stereo color fundus photographs,
fiuorescein angiographs, and photomicrographs Lo
illustrate some of lhe .in atomic and physio Logic altera­
tions produced by a variety of intraocular disease pro­
cesses affecting the macular region.
After a discussion of the normal macular region
(Chapter 1), the diseases alfecling this region w ill be con­
sidered in the following order according to the primary
Preface to the First Edition
tissue involved: diseases of the chomid (Chapters 2 to
4), pigment epithelium (Chapter 5), reLina [Chapters 6
Lo 10), viireous [Chapter ilj, and congenital pil of the
oplic nerve head (Chapter 12). \his subdivision is some­
what arbitrary in that it is not possible in some instances
to know which of the ocular tissues is primarily involved
by a particular disease process. Stereopholographs of
some ofthe fundus photographs are included in fifteen
reels, each containing seven views, attached Lo the hack
cover of the book. 4'he appropriate reel number (Roman
numeral) and view number (Arabic numeral) are indi­
cated in the lower right-hand corner of the black and
while photographs.
All fundus photographs were made with the Zeiss
fundus camera, fluorescein angiography was done uti­
lizing modifications'"' of the technique described by
Novotny and A Ivis. '1Kodak Kodachrome U and Kodak
Tri-X film was used.
W ith a single exception, Lhe fundus photographs
used in this alias were obtained from the photo­
graphic files of the Bascom [’aimer tye Institute of the
University of Miami. Most of the patients were exam­
ined by me.
I wish Lo thank [>r. I!dward W.D. Norton, Chairman
of the Department of Ophthalmology, the members
of the full-time and resident staff, and the many other
physicians whose patients are illusLrated in this book. E
am particularly indebted to M l Johnny Justice, Jr. and
his assistants. Mr. Kenneth Peterson, Mrs. Uixie Sparks
Cilbert, and Mr. Lari Choroniokos for Llieir skill in fun­
dus photography, and to Mr. Joseph Coren and Miss
Barbara French for preparation of the illustrations.
E'inally, E wish to thank Mrs. Margaret Eierlolami, Dr.
Alexander I?. Irvine, Mrs. Reva Murtes, and Miss Belli
Eiailinshafer for Llieir help in preparing and editing the
manuscript.
/. UanjjW jVf;
In Remembrance of Dr Gass
As a teenager growing up on Eiey
Kiscayne, 3 v№i]iid awake on school
days and leave the house in Lime to
catch ni 6:15- a.m. school bus into
town. On the way otil. I would find
my father, up since before dawn,
hard at work in lhe downstairs den
of our home, ihe images of him
pecking away on hit electric type­
writer with his four finger technique-
peering up aL slides, rummaging
di rough piles of bide* cards, and
painstakingly drawing illustrations
of the macula remain imprinted in
my memory. Jhis sccne repeated itself for many years
beginning in the late sixties. nThe book", as we called iL
around the house (we didn't know it as the "Atlas'7 hack
then), Was taking shape. In those days... we were always
aware of the presence of the book in (he background of
daily life around the Cass household. My father Wiis usu­
ally careful not to let it intrude on other family priori­
ties. but from time to time an increased sense of urgency
to meet some deadline would become evident. My
mother would often wonder out loud, soEnetimes with a
tinge of irritation, if the book would ever be finished. As
it turned out, the answer was not for at least forty years
and I am now honored to contribute Lbis foreword for
the fifth edition of Gass' Allas of Macular Diseases by
Anita Agarwal MD.
I'm not sure when E became fully aware of the pro­
found impact on the world of ophthalmology that my
father's work at fSascom Palmer was having, lhe family
received hints of this from lime to time, bearing stories
about my father from his colleagues and friends who
would appear at our house. A modest and Unassuming
person, we would never hear a thing about any of this
directly from him. Not being a doctor myself, it took me
some years to piece together the full picture, but over
time I became cognizant of the fact that Lhe man I called
"Dad1 -' had become a giant in his field.
My job has lakect me all over the world and ] have
lived on five continents. Over lhe years and until now,
I have been amazed by the number of encounters E
have had around the world with former colleagues, resi­
dents. felloxvs, students or patients who- knew my father
personally or were somehow influenced by his work,
in many cases via. the Cass Atlas.. I here are always the
comments about the impact of his research, his skill as
a teacher, or the brilliance of his scientific insights. But
1 also find., without except ion, that the comments from
those who knew him personally are accompanied by a
slory about some kindness my father had shown them
or an anecdote about how he had somehow touched
their lives. They always want lo tell me something that
3 already know... thal in addition Lo being a renowned
physician- Don Cass was a Very special human being.
Indeed, my father was an extraordinary person apart
from all of his contributions to ophthalmology. J Ее was
first and foremost a loving husband, father, and grand­
father who cherished his family, lo niy brothers and sis­
ter and me., he was "l}a d u. To everyone else in the family,
including bis five grandchildren, he was "D on17. Crowing
up. there was nolhiEtg E wanted more than lo be doing
something with him. ] can remember him Leaching me
how lo fly a kite, ride a bike, throw a spiral, shool a free
throw underhanded, and bow to fish. He took me to
baseball games, taught me howto read a box score, and
turned me into a lifelong Orioles fan. More importantly,
1 Learned from him what it means lo live one's life well,
by observing over the years the most powerful example
of this 3 have ever seen. Whether one knew my father as
a physician, colleague, mentor, friend, neighbor or fam­
ily, he was respected and loved for his kindness, his gen­
tleness, his palience, his sense of humor, his integrity, his
steadfast faith in (he Lord, and a genuine humility rarely
seen in others^
When 1 was younger 1 often thought about what
motivated my father to get up every day before dawct
to write a book. 3 knew it was not a desire for fame or
recognition or Enoney. i could always see the constancy
of purpose and his passion for whal he was doing that
remained unabated until the day he died. 1 could also
sense the personal responsibility he lell for Lhe con­
tinued stewardship of bis work.- including (he Class
Atlas, because he understood it was itnportant. But as J
observed my father over the years. 1 came Lo understand
there was also something else that made him tick. it was
the simple yet deep satisfaction and joy that he got from
creating something, solving a problem, and complet­
ing a task well, hi bis later years, ] watched him become
an accomplished wood craftsman by applying the same
creativity, curiosity, dexterity, intention to detail, and
patience that made him a great doctor. He spent much
of his spare time in his wood shop crafting toys for the
grandchildren, furniture for Lhe house, or incredibly
detailed model sailing ships. Some of these projects took
hours; others took several years to compleLe. I loved
seeing the smile on his face and the twinkle in his eyes
which gpve away the pure joy and sense of accomplish­
ment he felt after completing even the simplest of these
projects. 1 am certain that is the same feeling be had jn
completing each successive edition of lhe Cass Atlas.
] am delighted and grateful that L>r. Anita Agarwal
who worked with Eny father in his final years at
Vanderbilt agreed Lo take on the challenge of authoring
the fifth edition of the Gass Atlas more than four decades
after the first edition was published. ] know that my father
woutd be very proud of her. Itie Cass Allas represents a
significant piece of my father's ILfes work and an impor­
tant part of his legacy. However, the most enduring legacy
of Dr. |. Donald M. Gass is. the one that lives on in the
lives, the careers, acid ihe memories of ihe people touched
by this remarkable man over the course of a lifetime.
fotm D. Cuss on behalf o f Jiiy m o lim Mqngy A рргг
bm lkcn CaiUon arid, Dean, ami m y sjjfer Medfrti
J. Donald jVI. Gass
Gendeman, Scholar and Genius
John Donald McEntyre Class was born on Prince Edward
Island, Canada on August 2:|<I 1928. At 2 weeks of age he
rode on a train with his mother from Canada to Nashville
to join bis father, a chest physician who had been named to
direct the tuberculosis hospitals in lennessee. He attended
the two-room Grassland primary school, which housed 3
grades iti each room. lieing exposed to the same lessons for
3 years, Don Cass mastered 3rd grade while still in first grader
leaving himself plenty of lime to learn more. ] Ее always
fondly recalled bis V1grade teacher, who loaded her station
wagon even,r monLh with books from Lhe library for her stu­
dents to read. 'Ihus, was bom his interest in reading. Several
years later, he mel his first and only lore, Maigy Ann Loser,
on their high school bus; ibey were married in 1950. He
attended Vanderbilt University for his undergraduate educa­
tion and was deployed to Korea soon after being married. On
his relum, he began medical school at Vanderbilt, graduating
with lhe highest honor: the E-bunder's medal.
Much lo his father's puzzlement, Don Cass chose oph­
thalmology, a field then in its infancy. I le spent his intern­
ship at the University of Iowa, and went on lo be a resident
at the Wilmer bye Enstitute at the lohns Hopkins Hospital.
I ll ere. he idolized Dr. ]:rank Walsh: whom he recognized
the inslanL Dr. Walsh walked in for morning rounds on
day one. While a resident, he wrote several papers on top­
ics ranging from the optic chiasm lo corneal iron lines.
Hetween his senior residency and year as Chief Kesident,
he completed a fellowship in ophthalmic pathology at the
Armed E'orces institute of Pathology. Ihis experience gave
him an insight into disease pathology thal he used skill­
fully through his entire career. He became quite facile in
describing and postulating the pathogenesis of anany dis­
eases, most often accurately. Many of these insights were
confirmed subsequently, using sophisticated lesls such as
OCT and aulofluorescence imaging.
His numerous clinical contributions resulted from a
unique combination of keen observation skills including
the evaluation of stereoscopic images, atlenLion to details,
ability to comprehend and explain symptoms, and an
uncanny memory for clinical findings among palients that
he may have seen decades apart, l ie could nol resl until he
figured out all aspects of a new disease. Dr. Gary Abrams
once told me thal when Don Gass came upon a new dis­
ease, he la Iked about it incessantly till he figured it out
completely in his mind. His excitement on seeing a new
or rare disease was palpable and spread lo his trainees.
E recall the twinkle in his eyes and the excitement in his
voice when he found (he 250 micron DU5N Worm coiled
up in the midst of several retinal scars. I Lis approach to
understanding findings was simple and straightforward,
and he used common objects Lo describe the analogy: a
bagel for ring shaped sub EtFE neovascularization and the
petalloid appearance of fluorescein staining in cystoid
macular edema. L-luorescein angiography was just intro­
duced as Don Gass began his career in Miami, his sludv
and interpretation of this investigative modality in retinal
and choroidal diseases has helped us understand a major­
ity of them, lo this end, the talented photographer fohnny
Justice at Rascom E^imer Lye Institute aided him.
Don Cass had a smipfr bus method to make
notes about Lhe various patients' findings, i Ее carried 4x6"
note cards in bis pocket and wrote down salient informa­
tion about a hitherto undescribed condition that he saw.
He cataloged them alphabetically When he saw a few
more palients with similar findings, he gathered all his
cards and began deciphering the findings. Jn this manner,
he described more than 30 original diseases and new fea­
tures of several others. Ihe descriptive names he gave Lo
these diseases such as acute posterior multifocal placoid
pigment epitbeliopathy, acute exudative polymorphous
vitelliform maculopathy, and acute zonal occult outer
retinopathy would provide the clinician insight towards
Lheir pathogenesis or pattern of involvement. His under­
standing of disease pathology was cemented by his draw­
ings. Many of his drawings are exact replica of whal we
now see on О С]' imaging; a feat lhal Don Cass achieved
several decades before the availability of О С Г imaging.
Elenderings of the pathogenesis of a macular hole, vilreo-
foveal tractionr type 1 and type 2 choroidal neovasculari­
zation. and the appearance of REM: detachments are just a
few examples.
]Tiis giant in our field was kind, humble and generous.
'Ihe transcriplionisl at Vanderbill Lold me of the largest
fruit basket lhaLshe had ever seen in her life arrive at her
doorstep when she was ill, sent by D r Cass, lie enjoyed
simple pleasures, such as fishing and woodworking. His
knowledge and interest in sports was evident during ani­
mated discussions on Monday at lunch about the iveek-
end's various sporting evenLs and results. Most of all- he
was a healer and Leacher, who made each one of us a bel­
ter doctor, a better teacher and a betler human being. We
were so privileged to have known him.
Written on behalf of all his sludentsr past, present and
future.
Ajrj'rrf Ag<iru\il
Normal Macula
ANATOMIC SUBDIVISIO NS
llie retina is a delicate transparent tissue of maximal thick­
ness (approximately £>.55 jnm) nil the foveal margin and
mini mat thickness at the umbo. Anatomically
the macula (macula iulea or central retina) is defined as
I hat portion of lhe posterior retina that contains xantho-
phyll a n J two or more layer* of ganglion cells. It mea­
sures approximately 5.5mm in diameter and is centered
approximately 4mm temporal to and О .й т т inferior to
the center of the optic disc [E'igure S.01) . 1 On the basis
of microscopic anaLomyr the macular area can be further
subdivided into several zones. The fovea [fovea centralis)
is a depression in lhe inner retinal surface in lhe center of
I be macula. It measures approximately 1.5mm [1500pm)
or one disc diameter in size, lhe central floor of the fovea
es caEled the foveola. It measures approximately 0.35 mm
in diameter. It lies within the capillary-free zone or foveal
avascular zone, which measures approximately 0.5mm
(500 цгп) in diameter in most patients. A small depression
in the center of the foveola es called the umbo. A 0.5-mm-
wide ring zone where the ganglion cell, imier nuclear
layer, and outer plexiform layer of itenle are the thickest is
called the parafoveal area. This zone is in turn surrounded
by a ].5-mm zone referred to as the peri foveal area.
CLINICAL APPEARANCE___________
Ophlhalmoscopically, the anatomic subdivisions of the
macula are ill defined (figure ].02),'lbe center ofthe macula
appears as a poorly defined, one-fourth to one disc diam­
eter size zone of greater pigmentation that is maximum
in lhe foveolar area. The foveal reflex, which is present in
most normal eyes, appears lo lie just in front of the center
of the foveola and therefore overlies lhe anatomic Litnbo.
There are no consistent ophthalmoscopic landmarks to indi­
cate Lhe margins of either die 0.35-mm diameter foveola or
the 1.5-mm diameter fovea. Jhe margins of the сарз Ilay-free
zone of the retina that in most patients measures approxi­
mately 500|im in diameter angiographically Cap only be esti­
mated biomicroscopicatly because lhe perifoveolar capiLEary
network is not visible. En younger palienls an oval or roucid
halo light re lex al lhe inner relinal surface may correspond
with the foveal margin [figure ] .02K).'l he foveal depression
can be visualized With the narrow slil-lamp beam.
BLOOD SUPPLY___________________
Retina
fhe blood supply lo the inner half of the relina is by way of
Lhe central retinal artery which usually divides InLo a supe­
rior and inferior trunk within the optic nerve head. Jhese
trunks divide into Lwo branches, one supplying the nasal
and the other Lhe temporal quadrant of the relina. lhe cor­
responding relinal venous branches have much the same
distribution as the arteries. Ibese mafor blood vessels lie in
f.OE Normal macula.
Л -C: Topiographic anatomy and iiiiitcipalholtjjjy of Ihe m ac­
ula. A, Fftvea containing (he.1 fovTtbfa (iiJ- capillary-free /one
(cfzl, bind umlit) (u:. Б, Pa Kb loves!. C, t^twifovea.
D: Ор1ка1 tCahtrerice tonography image o[1 be normal m ac­
ula corresponding Lo the histology sten 5л C.
1,r02 Variations in appearance of normal macula.
A: HrunelLo fundus showing moderate Lo heavy concen-
Lralion of piemen I in Lhe leLinal pii^m-c+nI epil helium LhjiI
obscures. mosL of Lhe cE»oroidal vessels. NoEe [he greater den-
sily of pigmenl i i the macular area, lhe? ciliorelinal arlery
tblacJ: arrow), a firs!-order arteriole ■;upper black and white
ariow.i, and a second-order arteriole (low er black and white
am w)i
B: Blond fundus. Cfioroidal vessels are visibte e v e ry w b a e
eaCepI in Lhe macular ,inea. The oval liji'nl reflex in lhe muc-
ula of Lhis-vexing child in located aL the mjirgin of Lhe lovea.
C: Tesseiated fundus in ald er pa lien I. Large chtoroidal vessels
are visible in lhe macular area because ol reEaLfve hvoopig-
menEaLion o f relinal piemen! epi Ihelium.
D: Heterochromia of the Hindus.
IА , Гхош i i i i a i . -" . A n iLTj<..in M r d i t .il -4s\r>: :;ilia n . A 7I
ftalHtVeJ.)
the nerve fiber kiyer close lo lhe internal Limiting membrane
of (he relina. 'Ihey give off arteriolar and venular branches
that posteriorly occur primarily al right angles lo the parent
vessel, lhe branching is predominantly dichotomous as they
course peripherally. The righl-angle branches are referred
lo as firsl-order arterioles and venules [figure 1.02Л). I li
approximately 20% of patients Justice and Lehmann- found
ibal a variable portion of the papillomacular area was sup­
plied by one or more ciliorelina] arteries derived from Lhe
ciliary circulation [Ngure f.02A). Occasionally a large cilto-
retinal artery may supply virtually the entire macula, 'lhe
relina] arterial circulation is ordinarily an end-arlery sys­
tem thal does not communicate with lhe blood vessels of
lhe choroid or ciliary body. The retinal arteries anil veins
are interconnected via an extensive capillary network ihal
extends oulwani lo the external border of the inner nuclear
layer. The blood vessel walls are normally transparent.1
lhe postcapillary venules join lo beeoEne relinal veins thal
accompany Lhe retinal arteries and exit through the lamina
cribrosa and drain into the superior ophthalmic veiti. lhe
relina] pigment epithelium (R $ tj and the pboloreceplors
are nourished by diffusion from the choriocapillaris.
Choroid
Ibe ophthalmic artery, the first branch of (he internal
carotid artery, divides inlo medial and lateral posterior
ciliary arteries, before entering the sclera each of these
divides inlo one long posterior ciliary (1.ЕЧ1А) and 5—]0
short posterior ciliary arteries [Si’CA). A total of two E.PCA
and 15-20 SFGA b are thus formed, lh e I.PC As pierce the
sclera 3-4mm from the optic nerve and course between
 ©
1,01
 ■i
4 A P T E R 1 Normal Vl-acida

the choroid and Lhe sclera along the 3 and 9 o'clock
meridians till they branch at lhe ora serrata. 4’hree lo five
branches bend posteriorly Hind supply lhe choroid Li I!
the equator. Lhe &PCA. enter (he sclera around (he oplic
nerve and course for a shorL distance in lhe suprachoroi-
dal space, then enter the peripapillary choroid and branch
anteriorly and posteriorly lo supply lbe choroid up Lo the
equator There are seven anterior ciliary arteries (AGA) that
accompany the four rectus muscles,- about S-3 2 recurrent
branches of lhe АСА supply lhe anterior choriocapil Laris.,
and the resl о Г the АСА form the major circle of lhe iris.
'ihe venous drainage of the choroid is mostly through Lhe
vortex veins and a small anterior portion occurs (hrough Lhe
anterior ciEiary wins. Fostchoriocapi Haris renules form affer­
ent reins thal converge into the ampulla of the vortex reins
(2 mm wide and 5mm long} in each quadrant. Eiach quad­
rant has one vortex vein; occasionally more lhan one is pres­
ent They are situated 3-3.5 mm behind lhe equator (Figure
L06D) atid drain into the superior and inferior ophlhalmic
veins. lhe superior ophthalmic vein drains a major part of lhe
globe and enters- the cavernous sinus after passing through
f .03 Cross dissection of a fresh human eye.
A: Fundus of lh e eye after removal af the anlerLo* jfljjm eni
partial loss thu normal retinal transpajlm di The
dark kiveoLn г spa) 1arrow) is caused by Ihe densely cu rten -
traled xantbuphvll and the retinal pigment epithelium iRFEiJ.
which is visible I hrough lhe lliin portion o f the foveolar reL-
ina. A halo ol" yellowiab color ■;кд ntfentjphy 11 in lhe retina sur­
round* (he dnirk spol.
B: Sflghlly magnified v ie w of (he same eye. Following
removal pi lh e semiupati-ue relina, the отап^е color of Ihe
RF'L, which is dens-и in lbe fovcaE area larcuwlr i-s visible.
C: Sam e eye following incomplete removal of the RF'E.
Compare i^realer density of КРЕ remnanl in Lhe m acular л red
(aififr^v) w ilh lha] surrounding lh e opiic disc; n^nd elsewhere.
NoLe Chat m 1hiн particular eye lhe darkness til Lhe macuiafr
area is prim arily caused by Lhe difference in Ihe densLLy of
lhe K FL and not E*v Lhe difference in concentration of Lhe
uveal me3anucyles.
D: Lye ,Hltjf removal o f Lhe chorciid. Approxim ately ]1 shorl
cilidrv arteries [arrowheads) perforate the sclera in the mid
periphera! m acular area. Two bfanchin^ shorL ciliary arteries
Fine evident n.it.il to the optic nerve head. Nole lhe iont; c ili­
ary artery nerve larruwi temfjoral lo Lhe macula.

the superior orbital fissure while Lhe inferior ophthalmic vein

enters lhe pLerygoid plexus via lhe inferior orbital fissure.' 1.04 Retinal xanthophyll,
Location and relative concentration of xanthophyll pigment
Chonocapillaris idolsj in Ihe relina in Ihe macula area. K P t. retinal pi ц т ил I
upLLhelium.
'lhe choriocapil Laris have unique features compared to cap­
illaries elsewhere in the human body. L'hey are 40-60|im in
diameter, as opposed to other capillaries Lhal are 5-l0|im of the choroidal vascular details throughout the poste­
in size, and have ihin walls with fenestrations measur­ rior fundus, tiven in very blond in d ivid u a l in whom
ing (j OG-ЙООЛ. 'Ihe fenestrations have a thin covering dia­ much of lhe choroidal vasculature is visible the choroidal
phragm and are more numerous on the internal side than blood vessels in the macular region usually are obscured
the external side, which has lhe endothelial cell nuclei. by the greater density of the 1$E*F centrally (figure I.02B).
Ihree to four red blood cells can pass through the chorio- ftpE becomes less pigmenled with age, and in brunette
capillaris at a Lime. L’ericytes are seen occasionally and gap patients the greater contrast between the larger choroidal
functions are present. Connective tissue, fibroblasts, and vessels and the surrounding melanocytes gives a lesselaLed
nerve fibers are present between the capillaries and provide appearance to the fundus [I'igure 1.02CJ. Often there is
support, ihere is a rapid transition from the arterioEes to the less pigmentation of lhe choroid and RPli in a segmental
capillaries, hence the large blood IIow in the choroid Jhere area of the fundus inferior to the disc in Lhe area of closure
is a central precapillary arteriole lhal breaks up into a lobule of the fetal fissure. Uneven distribution of melanocytes in
of choriocapil laris and empties into a peripheral poslcapil- lhe uvea may occasionally give a distinct heterochromic
lary venule. 'I here is regional variation in the choriocapil - appearance lo the fundus [Figure 1.02EJ).
Earis architecture. The lobular pattern of the choriocapil laris
is seen in lhe posterior pole, whereas near lhe equator the CROSS ANATO jVIY_________________
precapillary arteriole and postcapillary venule hare a more
direct connection through lhe capillaries,. and anteriorly lhe Jixami nation of the macular area with a dissecting micro­
choriocapillaris connects lhe arterioles and venules at righl scope is possible after making a coronal section through
angles, creating a ladder-like pattern. the pars plana of a fresh eye (Figure 1.03). 'llie retina
The KE*ii is more highly pigmented in lhe central macu- begins to lose ils normal transparency within hours of
Ear area than elsewhere; Whereas the amount of melanin death. Yellow pigmenl is apparent in lhe center of the
in the RPE is similar in alt races, the number of mela­ macula. It is highly concentrated in the foreolar area
nocytes and the amounL of melanin in the choroid are (i'igure 1.03A). If the central macular area of a fresh
greater tn more highly pigmenLed races. En Caucasians human retina is viewed in cross-sectionr the concentra­
the combination of lhe pigmenl in lhe R P t and lhe cho­ tion of the xanthophyll appears lo be maximal in the
roid imparls an orange or orange-red color to lhe fundus. outer nuclear and outer plexiform layers. Xanlhophyll is
In most pigmented individuals the ЛЕЧ: and choroidal also present, however, within the inner plexiform layer
pigment impart a brown color that obscures most or all inside the foreal area (E'igure 1.04). In monkeys the yellow
t .03
pigment has been localized by speclro photo metric ним ly­
sis lo all layers from the outer nuclear layer inward but
with the greatest concentration irt the outer and inner
plexiform layer central Ly.-"1 1 MicrodensilomeLry of relinal
sections of primate retinas suggests that the greatest con­
centration is in the cones axons centrally.3 Stereochemical
analysis has demonstrated evidence that xanlhophyll com­
prises iwo carotenoids with properties identical lo those
of zeaxanthin and lutein.11' 1' After removal of the semi­
transparent retina, the normal orange-red appearance of
the fundus is restored (Figure 1.03KJ. Ibis color results
primarily from the melanin within the RPE cells and not,
as often implied, from the blood wilhin the choroidal ves­
sels. lhe relatively dark area in the foveal region is prob­
ably caused primarily by the increased pigment content of
the КРЁ cells. 'Jhe relalive darkness of this area, along with
the normal orange-red color of (he surrounding fundus,
largely disappears after lhe ЙРЕ is removed with a cotton
applicator [E'igure L03CJ. Some of the relative darkness
of the cenlral macular area remains, however, because of
Lhe greater concentration of choroidal melanocytes in this
area, lhe large choroidal vessels in older patients appear as
yellowish white cords coursing through the macular area.
Ihis loss of choroidal vessel wall transparency in older
patients, nil though often referred to as "choroidal scle­
rosis/ probably represents a normal aging change in the
choroidal vessel wall and is not associated with significant
narrowing of its lumen.
After removal of the choroid, the entrance sites of the
short and long posterior ciliary arteries are visualized
[Figure 1.03D). The short posterior ciliary arteries are con­
centrated in the macular area, particularly along the tem­
poral margin of the fovea and the peripapillary area. In
the choroid they branch frequently and course outward
toward the periphery. Several short posterior ciliary arteries
enter nasal to the optic disc. The temporal long posterior
ciliary artery and ciliary nerve enter about 1Vi disc diam­
eters temporal to the center of the fovea. Melanocytes are
concentrated along either side of both of these structures.
HISTOLOGY_______________________
ihe specialized structure in the macular region accounts
for the predilection of certain disease processes to involve
this area and for the variety of ophthalmoscopic changes
peculiar to Lhis area. In the macula we find the thick­
est porLion of the retina (Figure 1.01 E>) surrounding (he
thinnest portion, the foveolar area, lhe normal reLina is
composed of a mass of interwoven neural cells with little
extracellular space. The relative Jack of extracellular space
is apparent only with electron microscopy, which demon­
strates cell membranes not visible with ordinary histologic
techniques. En the inner half of the retina there is exten­
sive intertwining of horizontally and vertically coursing
neural cell processes and blood vessels, all of which are
\.ОГ. H isto Iogy о t macula r and para in acula г rel ina.
Peripheral macula, Л: arid рвйГаГлфиЬг retina, 6J: shbwing
internal iiTTiiLin^ mufnbrane li), ganglion cell layer inner
|jiyxifonn layer lipj, irtner nuclear layer vnt). ouLer plejtifomi
layer or H en le ml, outer nuclear layer (о), external limiting
membrane (ELM),, and reCeplnf eleancnli; (r).
C: Schematic depiction of lhe Muller cell cone iMcc). g,
cell layer; H, Hun Ip nLive fiber layer.
It, jdiipltid Глзт £Jtfisu.1J, О 1993, AmeH.tip ,‘HL'diiн As.\rx.i,iii(>n. Ail
rij^ils ruMjrvod..
enveloped by lateral extensions of the Muller cell pro­
cesses. in the outer plexiform layer of Henle. however,
the long Muller and receptor cell processes radiate in an
almost horizontal and then oblique direction away from
the cenlral foveal area and are not interconnected by inter­
twining neural processes and blood vessels. The Muller
cells are modified glial cells .that provide the structural
framexvork supporting the neural elements of the retina.
Lheir nuclei lie in the inner nuclear layer. Anteriorly their
basal cell processes constitute the inner relinal surface,
which is lined anteriorly by the so-called internal lim it­
ing membrane, basement membrane, or basal lamina of
lhe Muller cells (Hgure 1.05). This membrane is relatively
thick in the macular region except in the area of the fov-
eola, where il is visible only by electron microscopy. Ihe
internal limiling membrane serves as an anchoring struc­
ture for the collagen framework of the vitreous. Jhe apical
or outer celE processes of lhe Muller cells extend external
lo the outer nuclear layer, where they are connected to the
visual cells by a system of terminal bars that constitute the
external lim iling membrane (E'igure l.O SB).1- ihis row
of tight junctions probably provides at least a partial bar­
rier to the passage of large molecules in either direction, it
probably functions on the one hand to protect the retinal
extracellular compartment from encroachment by subreti-
nal exudate and on the other hand lo prevent intraretinal
exudate from spreading into the sub relinal space.
An overlooked part of the fovea is the inverted cone­
shaped zone of specialized Muller cells composing the
floor of the fovea - Muller cell cone, first reported by
Vamada in 1969.1111 'ibis cone of Muller cells is likely a
reservoir for concentrated xanlhophyll and the primary
structural support for the foveola (Figure 1.05C). Ihe
apex of the cone was close to the outer limiting mem­
brane and the base formed the floor of the fovea centralis
and extended into the area of the divus in the peri foveal
region. The cytoplasm towards the apex of lhe Muller cells
appeared scant and optically empLy. it was denser towards
the base of lhe Muller cells; this is in contrast lo the greater
density of cytoplasm of the Muller cells elsewhere in the
retina lhe internal limiting membrane lining the inner
surface of die Muller cell cone Was thin (10-20 nm] com­
pared wtlh Lbat in the peripheral foveal area (1.5 pm }.1'1
HisfrJfjgy 7
8 I d iA PTI R ] N u rm al M a n ila
The retinal blood vessels are confined lo lhe inner half
of the retina. Eilectron microscopy has revealed that all
of Lhe major branches of lhe retinal arterial system have
the structure of small arteries I hat persists even beyond
Lbe equator.1 RetLrud arteries differ in their structure from
muscular arteries of the same size in other organs in
their Lick of an internal elastic lamina and their well-
developed muscularis. Posteriorly the arterial wall consists
of five to seven Layers of smooth-muscle cells; peripherally
this is reduced lo one or two layers, lhe relinal veins near
the optic disc have three to four layers of smooth-muscle
cells. I'hl muscularis disappears.. however, a short distance
from the optic disc and is replaced by fibroblasts. There is
controversy concerning the pattern of distribution of the
capillary network in lhe retina. PeLinal trypsin digest stud­
ies suggest a diffuse arrangement1,1,11(1 whereas injected
whole mounts suggest a two- or ihree-tier arrangement.1
Jlie superficial network is predominantly postarleriolar
and Lhe deep network prevenular. Ibere is a distincl radial
peripapillary capillary network thal arises at the optic disc
and extends along an arcuate course wilhin the nerve fiber
Eayer. Inis network richly interconnects wrilh the inner reti­
nal capillary layer.L? In the perifoveolar area, the capillary
network is reduced to a single layer of capillaries that sur­
round a capillary-free zone, which varies in size buE which
usually measures 0.4-0.5 mm in diameter (see figure
l.OOh below). I"he capillary-free zone is an important
fluorescein angiographic landmark in evaluating patients
with macular disease, [here is experimental evidence Lo
suggest thaL the capillaiy-fiee zone is normally vascular­
ized during the p ren aLai development of the retina. JusL
before or shortly after birth the capiIlary-free zone devel­
ops as a result of spoilLaneous capillary obliteration.1'' In
a few patients with normal visual function, all or pari of
this prenatal capillary network may persist inlo adulthood,
ihe retinal blood vessels, as well as all of those within the
central nervous system- are Lined by an endothelium with
tight cellular junctions demonstrable in electron micro­
graphs. I his peculiar endothelial structure constitules the
inner part of the blood-retinal and blood-brain barrier
system that is responsible for maintaining the extracellular
spaces of the retina and brain relatively free of extracellular
fluid.
ihe RPL is a monolayer of hexagonal cells densely
adherent lo one another by a system of tight cellular junc­
tions or terminal bars lhal comprise the ouler blood-
retinal barrier which maintains the sub retinal space in a
state of detuigescencc. ihe intercellular cohesiveness of
the ttPE is not easily disrupted. Snlerdigitalion of the api­
cal processes of the KPli cells with the rod and cone outer
segments of the retina provides only a tenuous adhesion
of the НИ: to the sensory retina. The RPL cells are taller
1.0b Normal choroids
Д: HisLulojjic sagittal fiactlq'rt. Retinal piyment epithelium
[left Lirrowi, Bruch's membran& (right arruwi, choriucapiilaris
(ccl, choroidal mtilanucyle Im), prec api 11a ry arteriole Ip), and
choroidal artery :caj.
ti: Three-dimensmnal schematic representation. Note Lhe
lobular paLLerns ol lhe choriucnpiilaris with each tubule sup­
plied by an arteriole, ca, choroidal artery; cvr choroidal vein.
Cr D: Vbrte-it vein am pulla seen undtir lh e macula in Lhis
hij^h myope,, normally seen 14-1.5 mm from thy I i nil j u s ll>i
and contain a greater concentration of melanin pigment in
(he macular region than elsewhere.' ■' There is an inverse
relationship between melanin and lipofuscin pigment
concentration in Lhe pigment epithelium. Lipofuscin con­
centration increases initially during the first two decades
of life and then ag^in in the sixth decade of life, l he con­
centration of lipofuscin in the pigment epithelium is sig­
nificantly greater in white than in black persons. wrhereas
the concentration of melanin in the pigment epithelium
is similar in black and white persons. 'Ihe melanin con­
tent of the pigment epithelium and choroidal melanocytes
declines with age. In young and middle-aged individu­
als ihe tiPE-. is tightly adherent to the underlying Eimcb's
membrane by means of its own basement membrane, i'h is
adherence decreases with advancing age. [n Lhis hook the
term "Bruch's membrane" is used only lo refer Lo Lhe sheet­
like condensation of the innermost portion of the cho­
roidal slroma that consists of two layers of collagen, one
on either side of a layer of elastic tissue (E'igure 1.06). Ets
inner surface is smoothr whereas its outer surface is com­
posed of a series of waffle-like collagenous protrusions
that extend externally to form the pillars separating and
supporting the choriocapillaris. lhe inclusion of the sub-
mitroscopic basement membrane Layers of the PHL and the
choriocapillaris endolhelium as part of Bruch's membrane
by some authors is unfortunate for several reasons. First,
Bruch could not have seen these latter two structures with
lighl microscopy, and second, and more important from
the pathophysiologic point of view, it is logical lo consider
Bruch's membrane as being part of the choroidal stroma,
lhe condensation of mesodermal connective tissue thal
composes Bruch's membrane is similar in its relationship
lo lhe stroma ofthe choroid, as Bowman's membrane is m
its relationship to the slroma of the cornea. As an integral
part of the slroma surrounding (he endothelial walls of the
choriocapillaris, Bruch's membrane does not represent a
distinct tissue layer capabEe of being separated physically
from the choriocapillary bed. Because of its porous struc­
ture it probably plays a minimal role in regulating move­
ment of substances across il.
1.06
 lhe choroid is supplied by the abort ciliary or choroi­
dal arteries lhal are concentrated in the macula and peri­
papillary region. Posteriorly, these arteries form a rich
anastomolic network that quickly empties large quanti­
ties of blood into the sinusoidal network, referred lo as
the choriocapillaris. that is encased within the outer part
of Hruch's m e m b r a n e . J h e s e wide interconnecting
capillary spaces are lined by a fenestrated endolhelium
that is attached by its basement membrane to lhe ouler
collagenous zone of bruch's membrane. lbe choriocap-
ilSaris is arranged in a segmental pattern that varies with
h i location."4 " ," J'' In lhe macula there is a lobular pattern
of highly concentrated interconnecting capillaries sup­
plied by a central arteriole and drained by circuinferential
venules (i-igure I.06E>).:f'- ^ -
The peripapillary branches of the short posterior c ili­
ary arteries supply lhe majority o f the capillaries in lhe
prelaminar part o f lhe oplic nerve2' Although occasional
arterial branches from the dioraid supply the optic disc,
the choriocapillaris does not conim unicale directly with
Lbe optic disc capillaries. L'he prelaniinar capillaries freely
anastomose aL lhe disc margin w ilh Lbose o f lhe relina.
JJoth capillary systems drain into the venules leading Lo
Lbe central retinal vein.-"1"-1, IJ :1
lhe nutrition of the inner half of the relina es supplied
by the retinal blood vessels, lhe light cellular junctions of
the retina! capillary endolhelium (blood-inner retinal bar­
rier) and the RPH (blood-outer retinal barrier), although
permitting Tree exchange of water, nutrients- and waste
products between the blood and the retina, form a barrier
that prevents passage of large molecules, including pro-
Leins and lipids, into the extracellular space of the retina
and into the sub retinal space. 'Lhe oncotic pressure, exerted
primarily by the high concentration of intravascular pro­
teins, together with intracellular physiologic pumping
mechanisms wiLhin the RJPE and relinal capillary endothe­
lium. are important in maintaining the retinal extracellu-
Ear space and sub retinal space relatively free of water. 'L'he
RPL is involved also in lhe photochemistry of vision, lhe
phagocytosis of degenerated outer segments of the retinal
elements, and the transport of metabolic wastes from the
retina into the choriocapillaris.
'l'he peculiar structure of the choroidal vascular tree
in the macula provides this area with the highest rate of
blood flow of any tissue in the body. Ibis is greatly in
excess of that needed to meet the nutritional demands of
the retina" and probably funcLions to stabilise the tem­
perature environment of the retina, particularly in lhe
macular area.35 Ihe choriocapitlaris is the major source
of nutrition for the ЙРБ and outer retinal layers. Although
rapid-sequence angiography has demonstrated some
degree of segmentation of the blood supply to the cho­
roid in both normal humans and experimental animals,
the availability of many pathways of collateral blood flow
in the choroid is responsible for lhe infrequent demon­
stration of loss of visual function caused by obstruction
f.07 Schematic diagram showin g relationship of
choroidal circulation, relinal pigment epithelium
(KPE), and relina.
Fluorescein enters by w^v or the ophthalm ic arlety <OA) ijnd
the ihorL t iliary arl [tries -:-С1Лi inLo the blood vessels of lhe
choroid ahd small capillaries wjppJyljig the optic пвпда hegri.
The dye passes in a m ore circuitous route by w ay of the cen ­
tral relinal artefy (CRAl into lbe retinal circulation. In the
tnatula the т о го density pi^jneiiltjd pigment up il helium .and
lhe retinal xanthophyll act an idlers Lo obst ure Lhe underly­
ing choroidal № ьёёяи from vitnv.
l l - ш т l i . i y r u h . " ' . ■ I 5 7 J . Л п ч т и .in iv l t i l .i . j Л ^ ы д 'и М ч п . A l l eig h ts
ratlVtd.)
1.08 Tech mque о I ftuo re scein a ngtog rap by,
Fnliejil (left), pholo^apher, and physician.
of lar^e choroida! arteries, particularly in the posterior
fundus, ’l'he choriocapitlaris, like the re&l of the capillary-
system outside the central nervous system, has an endo­
thelium with a pore size sufficient lo allow some larger
molecules, including proteins, lo escape into theexlravas-
cular space. Outside the eye, extracellular protein returns
lo the intravascular system via the lymphatic syslem. In the
eye there are no lymphatic channels, and the perivascular
and perineural spaces in the sclera probably function as
lymphatic channels to provide a pathway for extracellular
protein to exit the eye and to gain entrance into the lym­
phatic system. 'Jhus the choriocapiHaris endolhelium is of
primary importance in controlling the amount of extracel­
lular fluid normally present in lhe choroid.
NORMAL FLUORESCEIN
ANGIOGRAPHIC FINDINGS
Sodium fluorescein in solution when excited by a blue
light (465-490 nm) will fluoresce and emit a yellow-green
light (peak wave length of 520-530nm). Its molecular
weight of 376 is such that it diffuses freely out of all the
body capillaries except those in lhe central nervous system,
including the retina. It diffuses throughout Lhe extracel­
lular compartment, and it stains collagen, but it does not
enter the intracellular compartment in concentrations suf­
ficient lo be visualised. Approximately S0% of the dye is
bound to plasma proteins, mostly albumin. It is predomi­
nantly the unbound fluorescein in the plasma layer lying
between the relinal blood vessel wall and the column of
flowing erythrocytes lhal is detected angiographically.
In the eye the retinal circulation and the choroidal cir­
culation are separated by a filter of irregular and variable
density, the RPli (E-'igure 1.07). Huorescein injected rap­
idly into the antecubital vein of the normal patient (figure
1.0Й) enters the choroidal circulation by way of the
short ciliary arteries about 30-15 seconds after injection
 Choroic Reiina

i.oe
& I L i !A!’T I:K N o rm al .Vincula
(Figures 1.09 and 1.10). lhe choroidal flow is extremely
rapid; only with rapid-sequence phoLography can one
visualize the patchy choroidal filling that occurs in lhe
region of the shorL ciliary arteries. Rapid perfusion of the
choroid and leakage of Lhe dye from ihe choriocapil laris
produce a background choroidal flush that .has ,1 mottied
fluorescence because of the masking effect of the pig­
ment epithelium. Only in Lhe estramacular area before the
arteriovenous phase can details o£'perfusion of the larger
choroidal vessels be detected (Figures 1.00A and 1.10A 1
and A2). Elapid Leakage of dye from the choriocapillaris
and staining of tiruch's membrane give a ground-glass
appearance to the background choroidal fluorescence and
obscure all details of the choroidal circulation from view
(Figures 1.(}'.>B and L. 10til and 112). Lhe background cho­
roidal fluorescence is either absent or barely visible in the
norma! macular region, primarily because of the greater
density of the Ri*l. in this area and the presence of xan-
thop by II in the outer relinal layers. Ln darkly pigmented
individuals the increased density of the choroidal mela­
nocytes Ln the macula is also of importance in obscuring
the background choroidal fluorescence in the macula, in
most normal eyes, perfusion of any cilioretinal arteries
present occurs simultaneously wiLb that of the choroidal
Vessels and the capillaries of the optic nerve head, approxi­
mately I second before that of the proximal branches of
the cenlral relinal artery (Figure 1.0УА). Jn some persons.,
perfusion of the ciliary arterial system occurs simultane­
ously with or after the appearance of the dye in the retinal
arteries The dye perfuses the relinal arteries, passes into
Lhe capillary bed, and later collects at the margins of (he
Veins draining the area [Figure !f the bolus of dye
E5 given rapidly, Lhe major retinal veins may be filled with
dye at a time when minimal dye is evident in the arteries
(venous phase) [Figure ].ОУО). During the recirculation
1,091 Fluorescein angiographic study of the normal
fu n d u s.
Л: Prea feria l pfitfse jjjidWing the Tilling of ttie choroidal cir­
culation, Lind capillaries of Lhe optic nerve head larrow indi­
cates dye in moderate-sized choroidal vessel!. Mote patchy
b atkgrmj rid choroids I flus-li.
B: Larly arteriovenous phase (about 10 seco n ds showing
tilling of Lhe retinal artery and early laminar filling c l relinal
win.
C: LiiLer arteriovenous phase showing complete filEirg of
macuEar arterioles. Note laminar flow o f dye in veins (arrows
indicate, from right lo left, the retinal artery, first-order arteri­
ole, and second-erdef arteriole). Note ^round-j^lass appear­
ance of Ihc.*- b a ^ g iiifr id choroidal fluorescence ifial has
obscured from v ie w Lhe derails o f the choroidal vasculaLure.
1his is caused bv leakage of dye frum lhe chorioca pi Haris.
U: Venous slage showing maximum dye cdncErtfgLion in
relinal veins. .Note that choroidal vessels (arrow) appear non-
lIuonescenL. The spates bclw een lhe choroidal vessels, how ­
ever, appear fluorescent, because of leakage of the dye I hat
occurred in lhe inilia] pass of lEie dye through Ihe eye.
E: ГеП minutes after dyr injection. N<ile I ha I the dve is barely
visible in the choroid and relinal t irculatiun. Huorescence ol
Lhe opLit d iне. is prim arily caused by sLaming of the lamina
cribntrea.
F: M agnified view of normal m acula showing details o f perr-
loveal t apillary bed and avascular 2npe.
phases the outer edges of Lhe major retinaL vessels appear
relatively hyperfluorescent because of the greater amount
of fluorescein Ln the tangential section of the plasma cuff
near the edge of the blood vessels: Lhe dense RL3F in the
macular region effectively obscures the choroidal fluores­
cence and provides a dark background on which details of
the retinal circulation are displayed
 In many patients, particularly in those with a brunette
fundus, the tine relinal capillary nettvork, including I hat
surrounding the centra! avascular zone, can be visualized
angiographicalEy using the ordinary techniques of intra­
venous injection into the antecubiLal vein (Egure I.09E').
ihe diameter of the capillary-free zone is variable and is
usually 400-50t)|jm [one-third disc diameter). Serial
photography permits delection of ma^or flow alterations.,
whether caused by arterial, capillary, or venous obstruc­
tion. The detection of minor flow nille rat ions is difficult
without die use of cinematographic techniques. t he blood
vessels of lhe cenlral nervous system, including I hose of
[he retinar appear impermeable Lo the fluorescein mol­
ecule. ibis is nol true of blood vessels oulside lhe central
nervous system, including those of the choroid. Jhe dye
Eeaks out of the choriocapil laris, slains ttrueb's membrane,
diffuses into Lhe extravascular spaces of the choroid, and
eventually stains the sclera (Figure L. LO). ]usl as lhe reti­
nal vascular endothelium is a barrier to (he diffusion of
dye imo the retina, so the КГЕ: is a barrier to the diffusion
of dye from lhe choroid into the retina As die dye dif­
fuses into lhe body iissues and is rapidly excreted in the
kidneys and liver, (he intravascular concentration of fluo­
rescein decreases and dye begins lo diffuse back into the
choroidal vessels. !he Laige choroidal vessels lying in the
pool of exLravascular dye appear relatively hypofluorescenl
during the later stages of angiography [Figure 1.01Ю). Ihis
is partly because of a delay in the return of extravascular
dye inlo the choriocapil Earis, but more important! yr it is
a result of the greater amount of dye in the extravascular
spaces compared with the thin layer of intravascular fluo­
rescein surrounding Lhe cenlral column of erylhrocyles.
In evaluating diseases of lhe macula, fluorescein angiog­
raphy can be of value iti delecting: (1} alterations tn blood
flow; (2) alterations in permeability of lhe retinal blood
vessels; [3] alterations in the retinal vascular pattern; (4)
alterations in the density of the pigment epithelium; and
(5) other changes affecting the normal angiographic pat­
tern in this area.
In 1969- indocyanine green [ICC") was introduced as a
supplement Lo fluorescein as another dye for angiographic
study of the ocular fundus. weak fluorescent effi­
ciency o f ECG lim ited ils usefulness, however, until the
recent development of digital video imaging systems.'' "
ICCj is a water-soluble tricarbocyanine dye containing 5%
1.10 Fluorescein angiographic sludy of normal fundus.
Pertusion of normal choroid during angiography.
Compare angiogram (left) with schematic diagram
(rights Black dots indicate fluorescein molecules.
A l and A2: early perfusion of short ciliary arteries [scaf and
<. horiocapillaris \co producer early background choroi­
dal fEuoiest елее and fill я capillaries or lhe optic disc. RHL.
relinal pigment epjlhelium ; hm, Eiasemenl membrane.: E3M,
Kruch's membrane.
B l and 82: Arteriovenous phase showing Increase in back­
ground choroidal fluorescence caused l?v dye m olec li les
elstapJrtg iro n lhe cho-riocapil laris lo stain B ru ch s membrane
and [lie extravascular Ii унu -rit Ihи cEioroid. The dye docs nol
penelrate I be cell membrane ol Ibe relEnal pigment epithe­
lium, which is adherenl Lo Bruch's membrane by means of
lhe basement mem bra ne.
C l and С 2: Laler stages of angiography. Note the large cho­
roidal vessels are relatively IvypofEucnoHcenl I'arrcjwl. The
dye is d ill us mg back m1o [he chuTiocapi I laris as Lhe inLra-
vascular dye concent ration decreases. The large am ount of
dye in the exlravascular spaces and sclera in comparison
La lhal inLravascularly causes ibe larger vessels Co appear
hypofJuorescen L.
or less of sodium iodide, il has a molecular weight of 775.
When injected intravenously it es lighLlv bound lo plasma
globulins and is excreted solely by the liver. El has been
widely used medically since I У56 with minimal adverse
reactions.'' 11 Et should not be used in patients with a his­
tory of allergy to iodine. The principal advantages of ECXt
over fluorescein are its spectral absorption and fluorescent
characteristics in die near-infrared wavelengths. 3CG in
blood absorbs and emits light in the near-infrared range
(S05 and fl35 nm, respectively). Thus ICG angiography
atlows giealeT visualization through exudale, lipid, mela­
nin, and hemoglobin and provides a greater view of the
choroidal circulation than is possible with fluorescein
angiography, lieing more btghh piotein-bound than fluo­
rescein, it escapes more slowly from lhe choriocapil Laris
and new vessels into serous tissue spaces and, therefore,
in some circumstances is better able lo deled and Localize
areas of neovascularization Lying beneath serous detach­
ment of die pigment epithelium and retina.'1' En spite of
lhe increased use of ICJC angiography over the pasl two
decades, Lhere still exist some gaps in our knowledge con­
cerning lhe interpretation of iCG angiograms.
■j
n
"Я
1
p
2
о
Imaging and Electrophysiological Studies
PATHOPHYSIOLOGIC AND 2.0 E A ngi ographic d em on slra lio n о f btood flow
abnormalities in the eye-
HISTOPATHOLOGIC BASES
A: D elayed appearance o f fluorescein [20.2 seconds'I in reti­
FOR INTERPRETATION OF nal and choroidal circulation in pa lien I w ilh (jbslruction of
FLUORESCEIN ANGIOGRAPHY Lhe right carulid artery.
l>: Branch retinal artery alretruc Licm :arrow).
'Jhe anatomy and physiology of the choroid and retina О К г л п -Lh r e l i n a l v e i n u b s L r u c l i u n M a r r o w :.

and iheir relationship lo the normal fluorescein angio­ D: Per'HovetjIpaf retinal capillary occlusion,
t: LJelayed tierf"U4$tm □! Lhe choroid idark area'i caused Ijy cili­
graphic findings Were presented in Chapter 1 and are fun­
ary arLwiaJ (jcclubmn fallowing kryplon rad pholonja^uialion
damental lo understanding the principles of interpretation in papillomacular bundle area. Collateral drjjulalron to the
of fluorescein angiography in patients with ocuEar fundus choiiocapillariv was adequate Lo uneven I los-ь nl" visual acmLy.
ab norm aLilies. In this regard the following fads arc most r : Cunlrast I ^vilh normaf patchy areas \arrowsi o i delayed
important: choroidal jjurfuiiion by ihn short ciliary arleiies during eady
phases o f angiography.
1. Jhe choroidal vasculature and its extracellular compart­
lb, (rum L'uhi'n fl ;lI. 'l
ment are similar lo that of the body outside the central
nervous system in that ultrastructurally the capillary
endothelial cells have a pore size that permits escape of ABNORMALITIES OF BLOOD FLOW
relatively large molecules, including sodium fluorescein
W ith severe obstruction of either the carotid or the oph­
and some smaller proteins, into the choroidal extracel­
thalmic artery, there is usually evidence of delay in
lular compartment, which is погтплEly partly expanded
appearance of fluorescein in bolh the choroidal and the
by extracellular fluid.
retinal circulation (l:Jgure 2.01 Aft Jiecause of the end-artery
2. Jhe relinal vasculature and its greatly contracted extra­
arrangement of the retinal circulation and its high visibility
cell uEar compartment are similar lo that of the brain
angiographically, severe obstruction o f els circulation al any
in that the capillary endothelial cells are separated by
Eevel from the central retinal artery lo the central retinal
Light junctions ( blood -inner retinal barrier) that do
vein is readily delected angiographically [E'igure 2.01 B-D).
not permit escape of large molecules, including sodium
Jiecause of multiple posterior short ciliary arteries sup­
fluorescein and protein, into the relinal extracellular
ply ing the choroidal circulation and the rich arterial anas­
compartment, which is normally maintained in a state
tomosis within the choroid, angiographic demonstration
of re Ialive deturgescence.
of obstruction of one or more of the major choroidal arter­
3. Jhe choroidal circulation and its expanded extracellular
ies is infrequently demonstrated, liven when obstruction
compartment, which are nonnally stained with fluores­
occurs, collateral circulation is usually sufficient lo prevent
cein, are separated from the subretina I space and retinal
infarction of the overlying relina, as illustrated in Hgure
extracellular compartment, which are not stained with
2.01 E in a patient with ciliary artery obstruction caused by
fluorescein, by the relinal pigment epithelium (RJJb;
krypton red laser. IJapid-sequence angiography used in
blood-outer retinal barrier). The ЙРЁ is a monocellular
normal eyes often shows patchy areas of deEayed choroi­
layer of cells connected by tight junctions that prevent
dal perfusion in the posterior pole caused by minor varia­
escape of large molecules, including fluorescein and pro­
tions in the length and diameter of the short ciliary arteries
tein, from the choriocapillaris into lhe subreLinal space,
(E'igure 2.011-'), it may be difficult to differentiate these
which is maintained in a state of relative deturgescenoe,
changes from those caused by pathologic obstruction of
Jo assist in the regulation of the extracellular environ­
the posterior ciliary arteries. Peripherally, fewer pathways
ment, the choroidal and retinal vascular endolhelia, as
for anastomosis are available and occlusion of a major cho­
well as the ftPt, probably haw intracellular physiologic
roidal artery may cause a wedge-shaped area of ischemic
mechanisms that permit movement of molecules and
infarction of the KJ41 and outer retina [Amalric's triangle).
water against an osmotic gradient, in addition to these
After lhe disappearance of the white ischemic retina, angi­
functions, the R l'i. acts as an optical filter of irregular
ography usually demonstrates evidence of arterial obstruc­
density to obscure the choroid partly from view.
tion as the cause of the wedge-shaped area of RPB atrophy
Jh is. chapter briefly describes some of the basic patho­ (see Figures 3.56Еч and L, and 9.J51: and h). Acute obstruc­
physiologic and histopadiologic changes occurring in the tion of the precapillary arterioles and choriocapillaris is
posterior ocular fundus and illustrates how fluorescein usually accompanied by ischemic whitening of the RJ'H
angiography can assist in the detection and definition of and outer retina and a corresponding area of patchy Loss of
these changes. Additional details concerning specific dis­ choroidal fluorescence (E'igure '■). 15C-h). It is dirftcu.lt to dif­
eases are given in subsequent chapters. ferentiate these lesions biomicroscopically and angiographi­
In general, fluorescein angiography is useful in detect­ cally from similar changes that are unrelated to choroidal
ing [1) abnormalities of blood flow to or within the cho­ vascular obstruction (such as blocked fluorescence due lo
roid, optic nerve head, and retina and [2) lesions that alter opacification oi' the RPK (see discussion of acute posterior
the normal pattern of fundus fluorescence. multifocal placoid pigment epitheliopathy, chapter II).
 Angiography is helpful in delecting a focal area of
chronic obstniction of the choriocapillaris thal is accompa­
nied by alrophy of lhe overlying RVIL and retina. tfcorescei n
leakage in lhe normal choroid occurs primarily from lhe
choriocapillaris. Ef the choriocapillaris is obslmcted arigi-
ography may demonstrate perfusion of lhe large choroidal
vessels but Will show a delay in choriocapillaris perfusion
and late choroidal and scleral staining within lhe area of
overlying ИРГ atrophy (E-igure 2.Q1E:-H). karly staining
along lhe periphery of such lesions оссигъ from leakage of
fluorescein from the inlact surrounding choriocapiLlaris.
Angiography is helpful in differentiating Lhese focal areas
of 1113L, reLinal, and choriocapillaris alrophy from focal or
geographic areas of depigmenlation of lhe KPE: that biomi-
croscopically may appear similar (l-'igure 2.02A-E>). In these
laller instances angiography may show that the choriocapil-
Earis is relalively intact (see discussion of chloroquine macu-
lopathy, chapter 5).
"W IN D O W " DEFECTS
(TRANSMISSION
HYPERFLUORESCENCE)
IN THE RETINAL PIGMENT
EPITHELIUM CAUSING FOCAL
HYPERFLUORESCENCE
Focal areas of bypopigmenlalion, or thinning of lhe RI4:,
when associated with minimal or no alterations in the
underlying choriocapil laris, will appear hyper fluorescein
during lhe early phases of angiography because of the
grealer amounl of inciting blue light reaching Lhe cho­
roid and lhe greater visibility of the choroidal fluorescence
(figure 2.02A-E3). Stereoscopically, the area of the hyper­
flu оrescence appears flat or depressed and remains rela­
tively constant ici si/je throughout the sludy. The changes
in inlensilv of lhe fluorescence parallel that of the normal
choroidal fluorescence [figure 2.02A-[>). Areas of focal
atrophy or loss of the RETfi and choriocapillaris will cause
a delay in lhe early development of hypeiftuonescence
(E:igure im a - i fji
EXUDATION AND FLUORESCEIN
STAINING
Water and electrolytes are free to move back and forth
across the capillary endothelium. Ejrge molecules, particu­
larly protein and lipids, are nol, however, because of the
2..02 Hyperfluoresce n ce ca used by "w in d p w ,r d efe ct
in ihe retinal pigment epithelium fRPE>.
A —C : Fifly-ontJ-yetir-old wom an wiLh lupus e?ry1 hem alosus
and hu3J's-eye p.altedfi of dEpigrtlEntafifcib of the RPE Caused
by chloroquine. Mole evidence оГ early perfusion o f Lhe rela­
tively t r ia d choricicapillaris f o c i in B.
D : Diagram (jf v f iliСчЧI histopalholo^ic seel ion Ehnou^h l!k ?
m ac lfId of A F.liowinn depigrnentaljati or Fil’t (afimw^l
surrounding Llie central area of norm ally piymtmlud KI'Ei, and
inlacl undedving choriocapillriris.
E-G: ForEy-six-year-old рлМоШ with sotort! atrnpEiy and loss
ol lhe К PE: caused by Worthy's сепЕгаГ anuolar choroidal dys­
trophy. NoLe delayed choroidal perfusion in F indicative of
alrophy ol Ihe choriocapilEaris, and [ale fluorescein slain ing
of choroid rind ы:](.та in area of KF’b alrophy in G .
H : HisLopalhologic changes, including atrapEiy of KPE and
choricicijpillfms.
small capillary pore siix. JTie amounl of water lhal is pres­
ent in the extracellular space is determined osmolically
primarily by lhe pore size of the capillary endolhetiuni
and the amounL of prolei n within lhe exLraeellular space.
The amounl of pnolein normally present Lhere represents
a balance between thal escaping from lhe vascular com­
partment and lhal returning to Lhe circulation by wray of
the lymphatic system. When either elevalion of lhe iulra-
capillary pressure or pathologic altera Lion in the capillary
endothelium occurs, protein and in some cases larger lipo­
proteins and lipids escape into the extracellular space and
bring water with them (exudationJ.
[ntrachoroidal Exudation
Since fluorescein escapes normally from the choriocaptl-
laris, angiography is of little vaEue in detecting changes in
capillaiy permeability in the chnroid unless these changes
are associated wrtlh either loss of adherence ofthe НИ: lo
Bruch's membrane or damage to (he К Г t. blood-outer reti­
nal barrier.
Choroldat Exudation Causing Localized
(Disciform) Retinal Detachment
Localised detachment of the relina, often referred to as
disciform detachment, lhat is caused by exudale derived
from lhe choroidal circulation occurs primarily by ihree
mechanisms: (T) delachmenl of lhe JtE:E:; (2j choroidal
neovascularization; and (.1) devilalizalion of lhe RPf.
 it)
■r. ■
Detachment of the RPE
lh e normal adherence of the RI4i basement membrane lo
the inner collagenous /one of Bm chs membrane may be
disrupted by a variety of causes, including increased per­
meability of the choriocapil [am. degeneration of Bruch's
membrane, degeneration of the ЩРЕ anti its basemenL
membrane, and exudation from sub-RHi choroidal neo­
vascularization. Whatever lhe cause, serous exudation
from the choriocapiHaris or from sub-l?L:b new vessels may
produce a sharply defined, often blister-like, detachment
of the ЙРЁ [E-'igure 2.03).- Hi size varies from sub bio mi­
croscopic lo several disc diameters or larger. When the RP1:
detachment is riot caused by choroidal neovasculariza­
tion, it is usually round or oval in shape and less than one
disc diameter in size. It appears solid, and its color varies
from that of lhe normal orange-brown ЛРЁ to yellow-gray.
Jhere may be a pinkish rim of subretinal fluid around the
edge of the RPt detachment [b'igure 2.03). When small,
an ftPE detachment may be seen best in side illumination
with thesliL lamp. When caused by choroidal neovascular­
ization lhe serous RPt detachment oflen has a kidney or
notched configuration and bio microscopically and angio-
graphicallv demonstrates features suggesting the presence
of choroidal neovascularization [see discussion in the nexL
section). En nonvascularized serous RPli detachments fluo­
rescein molecules rapidly diffuse from the choriocapi I laris
across the full extent of the normally permeable Bruch's
membrane into the sub-RPK exudate lo produce the
pathognomonic stereo angiographic picture of a sharply
Localized area of fluorescein staining (figure 2.П.э). '['he
Angiography showing sequence of events in a
37-year-old man wilh a large serous detachment of
retinal pigment epiIhelium [RPE} surrounded by a
marginaE serous detachmenl of Lhe retina.
A I : K'ole light-colored, [JViL?,. serous deLiichmenl ol" Iby KFnt
strrfQunded (ту llit1 dflrier halt) ftf serous relinial dctach n i еп I
that extends inferiofly Id the i n-foncjN.'jn рог л I artery. Arrow
indicates several small param acular serous detachments of
the HPb.
A 2: Schematic diagram depicting serous detachment of the
HPt nind retina (Kj. io o n afler inje?c: Iiun of fluoresceSfJ, dye
molecules (black dotsJ enEer the choroidal circulation and
begin to diffuse* oltI of the cbariocapillari^ (ccl into Lhe exlra-
vascular spaces of the choroid and across Bruch's membrane
iBM^ into the sub-RI-’E space fcKs)-
B l and Б2: The dye poo It in [he sub-RRE space EjuL dues not
entp f.A e bubretinal ырлсе (ыКз..
C l acid C.2: Later the: dye outiines the area of detachment of
lhe b?PE. Although lb?1 fluorescence of the sub-ftPE exudate
begins lo fade as Lbe dye dilfuses back into the choriocapiE-
Earisr it is stiEE easily visible 1 hour after dye injection.
IAI. ti I. -iint 1IrumG.iKb. c;L.:l
fluorescence typically appears slighdy Laler lhan the back­
ground choroidal fluorescence and becomes maximally
intense later and persists longer than the surroumling cho­
roidal fluorescence liven when the RPH is detached, its
blood-ouler retinal barrier may remain intacl and prevenl
exudation into the subsensory retinal space [E'igure 2.(14).
 ttnnm

tmtm

Заеч
 A serous RPf detachment may cause loss of centra! 2.04 Disciform macular detachment. Exudative
vision in two wgjrsi Ji may enlarge concentrically until it detachment of the retinal pigment epithelium (RPE)
extends beneath the center of the macula (figures 2.03 and retina wi4 hout Сho roida I ne ovas с uIar iza tion.
and 2.04), or the detached R[TEi may deconi pen sate and
permit large molecules and water to enter the suhretinal
2.03 Developmental stages of occult type I
space and detach the retina [E'igure 2.04}. if the break­
sub-retinal pigment epithelium (RPE) choroidal
down in the ШЧ-. barrier is low-grade and not associated
neovascularization before retinal detachment,
with a physical break in the continuity in die RPf. fluo­
rescein molecules may not be able lo diffuse across the A: Chafiota рМЗдгу (ccj invasion оГ Hrurfr's membrane LBM).
detached R P f into the subretina[ exudate in concentra­ l-Wforation o l Brush's mumbranE? and ujrtnvlh bertfcath lhe
mlii’ril piymCht epithelium.
tions sufficient to be visible angiographically (see E'igures
2.03 and 3.03A-C). In the presence of a break, however,
fluorescein streams into the sub retinal exudate (see Figure
3.03 D-l).

Choroidal Neovascularization of the sub-RI’h space occurs, the new vessels establish a
tinder a great variety of circumstances, neovascular tufts relatively firm adhesion to the overlying RPh. Initially, the
arising from the choroid may either invade and perforate blood flow through the neovascular network is sluggish
Bruch's membrane or grow through defects in E3ruches and there is little or no exudation (l-'igure 2.0ti). During
membrane and proliferate in either the sub-RPli space this period of occult neovascularization, the overlying
(type E choroidal neovascularization) or in the subsen - retina and 3?ME-, may be minimally affected, and the net­
sory retin.il space (type 11 choroidal neovascularization).' work may not be detectable bio microscopically or angio-
lhe location and growth pattern ofthe neovascular protif- graphicaEEy {figure 2.06A and Б). Iltese occult neovascular
eration are determined primarily by the age of the patient complexes may be one disc diameter or larger and may be
and the pre-existing disease. irregularly or focally elevated inlo a mound by virtue of
proliferation of accompanying fibroblastic cells and new
Type I Sub-RPE Neovascularization vessels before development of evidence of the escape of
As part of the normal aging process as xvell as in certain exudate from Lhe blood vessels (figure 2.06C). With act
degenerative and dystrophic disorders (e.g., age-related increase in blood flowr through the network, the endothe­
macular degeneration and pseudoxanLhoma elasticum), lium decompensates, particularly at the outer margin of
the firm attachment of the ЙРЕ and its basement mem­ the network, and exudation extends into the subpigment
brane to the inner collagenous zone of Bruch's membrane epithelial space around the network. In such cases when
becomes loosened. En these patients new vessels extend­ the overlying RE^L is thinned and only slightly detacEied
ing from the choroid through liruch's membrane find little by serous fluid, details of the neovascular network in ay be
resistance lo their lateral growth into the sub-RPli space easily detected angiographically, even though biomicro-
(figures 2.05 and 2.06).1 I heir pattern of growth often scopically the ncLwork may be hidden from view by cloud­
simulates that of a sea fan or cartwheel with radial arteri­ iness of the exudate (figure 2.0S). lhe exudation may
oles and venules supplying and draining a circumferential extend through the ftPt and detach the overlying retina
dilated capillary sinus (figure 2.07). As neovascularization (figure 2.0УА and fi).
 RPE

Asynp:crna1k згпг I RPE d t :a c n n E n l

Зупрйгпэнс rEtna1dEtotfimenL
2M
 In oilier patients, exudation may begin at one margin
of lhe neovascular network and един: serous. detachment
of a large adjacenK area of KPE. Because of lhe relatively
firm attachment of lhe RPE lo lhe neovascular mem­
brane, these serous detachments of lhe KpE typically have
a reniform or notched shape as a result of their develop­
ment around lhe margin of the network, most of which
lies ouLside the area of RPE detachment within lhe notch
(t-'igures 2.t)9C-t and 2 .10A-C). lhe presence of the new
vessel membrane within lhe notch may or may not be evi­
dent angiographically as a mollled area of early hyperfluo­
rescence with or without some evidence of ill-defined [ale
staining. !f the detachment extends away from the enlire
border of the membrane, it may assume a doughnut con­
figuration (figures 2.09E and 2. JOil). If a highly elevated
serous detachment of the overlying as well as surround­
ing StpE occurs, the choroidal neovascular network will be
completely obscured bio microscopically and angiographi-
cally by the RPE detachment, which usually has an oval or
round configuration ( E'igure 2.0'Jt').
2.06 P re-evil dative stages of development of occuit
type 1sub-retinaf pigment epithelium (RPE) choroidal
neovascula rizat ior .
A: EarlS E3Vt. E3ruth's me.TnEjr;mo.
hLiC ncnvi^suuliir пгюгпЕклпо.
С: Eleva& d fibm yisdjJlar complex.
2.07 Growth pattern of choroidal neovascular
membrane, frontal view.
Cnu.Vi-lh Ьсэдт-ь with ь т л ]] capjihtry loop (1) e?xlending
ЬедааИЬ yithur lhth retinal рщлтс'п! t-'pilhuIiиm Ctype ll ot *en-
ыогу rcliita (type 911 and expands intu ^ ЗзВДе пел 1дл-shaped
Lomplex ;A\- with well-difFerenliated radial retinal arteries
0hd исты and a d ia le d cirt и rnEumnl ia I £лр:!1дгу ntflwoik.
AV*
 Leakage of large prole ins and extravasation 0 f erythro­
cyte s from the neovascular complex. causing large serous
ПРЁ detachments, often produce other biomicroscopic
and angiographic clues lo Lhe presence of neovascular­
ization. IJio microscopic clues include yellow sub retinal
and intraietinal exudate or blood near the margin of lhe
detachment I see Hgure 3.02L>), dark sub-RPE '"'fluid
Levelv at the inferior edge of the detachment (see ligure
3.19C), and uneven elevation oJ" lhe detached RPE not
explained by gravity. Angiographic clues to lhe pres­
ence of occult neovascularization include delayed and
incomplete stain mg of Lhe sub-]?ETEi exudate (see Figure
3.21). lhe neovascular membrane is most likely Lo be
Located in the less fluorescent zone of greatest opaci­
fication of the sub-RE’E: exudate. Accurate Localization
of new vessel membranes lying beneath large serous
RPE detachments, however, is not possible with fluo­
rescein angiography because of rapid movement of lhe
dye through EJruch's membrane throughout the extent
of the detached K P E En ihese types of R PE detachments
computcr-enhaneed indocyan ine green [ECG) angiography
appears to provide a more accurate means of localizing the
2.OS Sequence of events during angiography in a
70-year-old man with loss of central vision caused by a
type 1sub-retina I pigment epithelium (RPE} choroidal
neovascular membrane (CNVM).
A l : The arntiws indicflle Ihe local ion ol" [he faintly J^ray
C N V M . Ttiare rs a small amounL o f blood benealh lhe RHE at
Lhe margin Qf lhe C N V M .
A2: Schema) к diagram depidinjj serous de4achment rjt Lhe
rt’Linu overlying a C^V.Vl lying in lhe sub-KI-’E sftace. Sotm
afLer injecLion of fluorescein, dye m olecules i black dots?
enlei Lhe thorctidal изjc llI лIion and begirt Lo perfuse the
L S 'V M lyinu iit Che suEi-FifE space.
B l jn d В2: Details ol Ihe C N V M are outlined by fluorescein.
C l and C2: D ye кмкн Ггогп Lhe C N V M and stains tht1 еки-
dale but nol lhe bJood Inonfluoiescenl area;-. in ih esub -K Ft
space.
sub-RPE new vessel membranes.' ICC dye is tightly bound
to the serum proleins and gradually slains the choroidal
neovascukir membranes [C SV M s) but does not, as occurs
with fluorescein, diffuse rapidly into the sub-RE^E exudate.
—^ . . —Я — Mr-
 Detection attd accurate localization of choroidal neo-
vascular networks may be difficult because of rapid dif­
fusion of iluore&ceio into tbe exudate overlyittg and
surrounding the network. variability of blood flow within
the network, and partial obscuration of Lhe network by
cloudy exudate, blood, or melanin pigment. Ihe use of
stereoscopic fluorescein angiography Lo detect irregular
nonlit ain ing areas of shallow elevation of the RPH caused
by occult neovascularization- and detection of other bio-
microscopic and angiographic clues to the presence and
Location of CNVJVls art' important to the proper manage­
ment of the palienl
2.0l"J Disciform exudative macular detachment
caused by type I sub-retinal pigment epithelium ■
!RPE)
choroidal neovascularization.
A: L irly serous reliital dtfladim enl.
Serous reCinal delac hment.
C: itfrouh detach т о п I erf the flfljaCfifil K}'L.
D : fibum jiscLilar deladim enL o f KPE and exuda Li w delafh-
inejnt of adjntenL Fi^E.
i\ M uRjIflbed or ппц SLfruuH RPL deEachmerit.
F: i^rculs detach mtfrH ctf Ibe overly in^ К PE.
-F \ v >
l !V Л Л i *■
■■-1
Type il Subretinal Choroidal Neovascularization
lyp e 11 subnet inaL choroEda! neovascularization occurs pri­
marily in younger and middle-aged palients with acquired
damage lo lhe choriocapEl laris-Bruch's raem brairf-RPE
complex caused by focal choroiditis (presumed ocular
Liistoplasmosis syndrome, punctate inner choroEdiiEs..
serpiginous choroiditis* toxocariasis), retinochoroiditis
(toxoplasmosis), trauma (choroidal rupture}, choroidal
hamartomas [osteomas}, optic disc anomalies (oplic disc
drusen, optic disc pits, and colobomas), and retinal dys­
trophies (Best's disease].' En these palients.. new blood
vessels extending From the choroid ill rough the acquired
defects in Hruch's membrane as ihey grow laterally in lhe
subretinal space encounter the firm adherence of the sur­
rounding RETti to the underlying Bruch's membrane. The
path of the advancing neovascular complex is therefore
directed anteriorly beneath the sensory retina ralher than
benealh the R P l: (figures 2.11 and 2 .12). .As the capil­
lary network enters the space beLween the retina! recep­
tor cells and the apical processes of the il stimulates
the R P b cells to proliferate and to atlach themselves by
Lheir cell bases to the advancing sheet of new vessels in
an effort to envelop them, This reactive RPE prolifera­
tion initially results in a zone of hyperplasia of the RPE
at the advancing border of the membrane, often pro­
ducing a hyperpigmented ring ophlhaimoscopicaily. As
the fibrovascular membrane continues to expand later­
ally into the subrelinal space, a monolayer of inverted.,
variably pigmented RPE cells wiLh their base directed
toward the new vessels grows along the posterior sur­
face of the membrane, '['his inverted layer of RPE cells is
firmly attached by the base of the RPE cells lo the poste­
rior surface of the membrane, and is loosely attached by
the apical processes of Lhe R P E Lo the apical processes of
the native R P E . Anteriorly (he proliferating layer of RP1I
cells has more difficulty keeping pace with the advanc­
ing neovaseular membrane thal is usually separated from
the overlying relinal receptor cells by a layer of subretinal
exudate (see chapter 5 for climcopathologic correlations
of type II membranes). BiomEcrcKscopEcally this expanding
fibrovascular membrane lypically produces a gray or partly
pigmented subretinal sheet or mound of tissue extending
away from the edge of the pigment ring. This is usually
accompanied by varying amouLils of subretinal exudate
and/or blood. Lxcept for the tendency for the new vessels
to grow in a sea fan configuration in both lype I and type
2.Ю Patterns of serous detachments of lhe relinal
pigment epithelium (RPE} caused by lype 1 sub-KPE
choroidal neovascular membrane fCNVM: stippled
area).
I: R PE delaciinnenls. OLCuirtny д1 lhe margin o f [he C N V M .
IСогпрлг-е A, B, n.nd С with Figure 2.Q4C, лпН U r and p w ilh
Подите 2.09L:.l
II: H.PE d eL^b m i’nt ovErlylfig lliu C N V M (cam ppte wi*h
Fij^LiTE? 2.0fiF|.
11 neovascularization, their pattern of growth other vise is
distinctly different histopathologically. In spile of these
histopathologic differences, however, biomicroscopically
and angiographically the two types of neovasculariza­
tion are not always easy to differentiate from each other,
'lhe presence of a black or slate-colored subretinal halo
or mound at the site of origin of the new vessel and the
absence of evidence of either solid or serous RRE delach-
menL suggest lype II neovascularization. With further
fibrovascular proliferation, exudation, and hemorrhage the
pigment halo or mound may he obscured and there may
he no biomicroscopic clues to differentiate type I from
lype 11 neovascularization. In such cases lhe age of the
patient and the nature of the underlying eye disease are
most important in determining which type of neovascular­
ization is present. Patients under 50 years of age without
evidence of retinal dystrophies affecting the i?PL-Bruch's
membrane complex, e.g., pseudoxanthoma etaslicum and
pattern dystrophy, are most likely to have lype 31 neovascu­
larization. Determination of the lype is of relatively little
importance in regard lo indications add techniques used
for laser photocoagulation treatment of the membranes.
Differentiating the two types, however, is important if sur­
gical excision of lhe new vessel membrane is contemplated
(figures 2.11, 2.12, and 3.52).1 lixctsion of type II mem­
branes allows (he sensory retina lo reattach to the under­
lying native RPE, and in some cases there may be excellent
recovery of visual acuity (Figures 2.12 and 5.5 2). * Excision
of type I membranes, on the other hand, results in loss of
the native RPE and an absolute scotoma corresponding
to the site of the membrane (Hgure 2.15]. Thus surgical
removal of lype I sub foveal membranes appears to offer
no advantages over laser pholocoagulation in regard lo
visual rehabi Eilat ion or preservation and has the disadvan­
tage of risks associated wilh one, and in most cases two.
i ntraocular ope rat ive p rocedu res.
 Whereas patients with presumed ocular histoplasmosis
and ihose with age-related таси'аг degeneration are the
prototypes for type 33 and type [ choroidal neovasculariza­
tion respectively, both types occur In patients wilh other
disorders or with no evidence of a primary ocular dis­
ease. Age and the presence or absence of a diffuse dystro­
phy affecting the structure of the choriocapilEaris-Elruch's
membrane-pigment epithelium complex are probably
the two most important factors delerrnining Whether lhe
growth pattern of choroidal neovascularization ivitl be
type ] or type 11. ChoroEdnd neovascularization deveLopitig
in a pa Lien l with presumed ocular histoplasmosis beyond
50 years of age may be type E rather lltan type tL Likewise,
some patients less, than 50 years of age wilh chorioretinal
dystrophies affecling, the attachment of the pigment epi-
Lhelium to Bruch's membrane (familial cl ruse п.. cuticular
drusem pseudoxstritholfia elasticumr pattern dystrophy)
may develop type I neovascuEarization,
.
2 1 E D ia g r a m o f ty p e IE s u b s e u s o r y re tin a l
n e o v a s c u la rizat io n .
A, B, and C: Early invasion oJ choroidal capillaries (cc) and
fibrucyles ihrough a detfedt in bruch's membrane and relinal
pigment epi I helium iR P i. inlo the subfetinal space. K a le ir>
E3 ar>d t Lhe readm e ргпМГстаМоп of HPE cell? around lhe
margin uf Ihe sutjreliital new bltjod v e s s e l and early fhverii
nion and all^chment of К PE c el к Lo ibe posterior huitace of
lhe new vessels.
D and E: Sheellike j^owth of new capillaries, fibroblasts.,
and inverted layer o f K Pt cells into lhe subjolinal space sur­
round lhe defecL in Bruch's membrane and R P t. K ole a I
lhe l-p-уы aclively growing edge of Lhe defect it, атге^ Lhal
lhe RPEi tells have extended on lu Line anleriuT surface o f lhe
neovascular membrane in LbeEr allempL Lo envelop Lhe
membrane.
 RPE

V f4V l ^ l V P l^ L r'l'jl'llL l^ rn 1
l“ ■1ГЛ *■
■
г-+
л-. *Г%"-Л> *-Vi-.-VVprf1

ш Ш в ш й й ш
 Chronic choroidal congestion associated with increased
eKtrava^cular protein and water (ciliochoroidal edema and
detachment) may overwhelm ihe ntbiliLy of the К E'E:. Lo
prevent passage of protein and wale г inlo the subnet inal
space. Initially, this may occur in the absence of any bio-
microscopic or angiographic evidence of RFE damage. Ihe
transport of protein across the RE1Г is apparently so slow
and widespread Lbat angiographic evidence of leakage of
fluorescein dye across the RLnb cannot be demonstrated in
most patients with combined ciliochoroidal relinal detach­
ments., at [east during Lhe early phases of lhe detachment.
I.ater. hyperfluorescence caused by RPfc atrophy and by
irregular areas of fluorescein slaining at lhe Eevel of the RPli
may occur in patients with long-standing detachment (see
discussion of idiopathic uveal effusion, see Chapter 3).
2, 12 Surgical excision of lype II subretinal neovascular
membrane,
Л: Type II tteovasCtlE^ memb-rani:1 has extended ihrtMigh a
defect En Bruch's membrane ( В т : arnow&L is covered un ib
posterior surface an adlmienl inverted Зауег <jf mtinal pig­
ment eprthuii и m .KPfc celb-,, Lind is loosely adherent I и lhe?
underlying native KF’t cells arid the 6 verlyi'ng 4et1i<Sry relina
e^trpL ill lhe site of Ijtuch's m e m b ra ™ defeLl. ct., choroidal
c-apil lanes.
В and С: I h r surgeon bns graspE^d w ilh t'oncept Iupon arrow.
Lhe neovascular membrane lb.H includes Ihe inverted KPfc
all ached Lo ils outer suhfate with forceps '«pen arruw., iias
deLachod i1 from its situ oE o rig ^ , and is s-lid i-пц if Ihrough a
mlinntumy.
D: l'!i i-s allows Lhe reLinal receptors lo be rfj-apprujiimaLud 1o
Lhe n.Hive KFb tplls posloper.H ively. Seu Ligure 3.5.2 fur fundus
photographs and photomicrographs of type II rnemhranes and
their surgical excision. Compare Lhis figure tarlth diagrams of
surgical excision o f Lype 1 membranes in Figure 2.1 i.
Tyre £Choncida! [нЯввдЬгаДОп
2 J3 Surgical excision qf type ( sub-retinnE pigment
epiiheliirm (RPE} neovascular membrane,
A and E: Type I neowa-iclita г membrane lias invaded and
eKlErtned ihnjuyh Qruch^S т е т Ь т а п е [arrows) and betiealfji
Lhe KKt. The membrane is loosely adherenl Lo lbe inner
surface of E3r-ui:hfs membrane but is im ply atlached an ils
anterior Surface ю Lhe i:alive KKE. w hich in turn is looseJy
adherenl Lo the overlying sensory relina.
C: The surgeon's fo rc tm Lopjen artfiW) ex lends ihrou^h a reLi-
nutomy and has ^ rapped Ihe neovascular membrane Lhal lies
benealh and is firmly a LI ached to Ihe nalive KFJt.
D : hallowing removal of 1he membrane, 4vhi-ch in tJ'jd es
lhe nalive K J'L Ihrou^h lhe relinotomy, lhe surviving relinal
receptors will lie against the inner surf a te oi Hrut h's mem­
brane and visual l"unet ion in this area w ill be losl.
 tbdy OCCUl! E-tdDt

®
Devitalization o f the RPE 2.14 S e ro us re lin a l d etac h пае п I ca u se d by
d e v ita liz a tio n o f lh e re tin a l p ig m e n t ep ilh eEru m (R P E ),
Breakdown of the RP£ bload-outer retinal barrier and
exudative retinal detachment may be caused by cither Л -С : ^егоиы detachment d I the m atuLi in a J'-4-yEar-bld ^irl
□cute or chronic devitalization of the RPE. A variety of w ilh acute disseminated lupus eryEhemaraffifii. N o le mu hi fo­
acute. inflammatory, ischemic toxic, or traumatic insults cal areas, of leakage af fluorescein Ihrough irfancied RF’t inlo
thy subrelinnl exudate.
lo lhe RPE: may cause exudative detachment of the retina
D : RhmI infarction of Ihe K P t [aJTuWrt] caused by iDCal
(Figure 2.14). These include inflammatory cell infiltration
occlusion o f choriocapillaris. Fine black idols- indicate fluo­
of the choroid (e.g., Elarada's disease, sympathetic uveitis rescein molecules. В т , К ruth's membrane; c c r choiS&idal
and posterior scleritis; see Figures 11.27 and 11.23), neo­ cap il Inлек.
plastic infiltration of the choroid (e.g.r melanoma (see E r F. and G : Serous retinal detachment caused by diffuse
Figure 14.12], metastatic carcinoma (see Figure 14.30), lira nLi It mia I d u e ini ill rati cm o f [he choroid in a ttfbtaari w ilh
and leukemia (see Figure 14.34)), acute occlusion of lhe Harada's d iкелье. K a le mullip-le pinpoint foci o f leakage of
fluimesCein dye ihrxju^h damaged
choriocapi Haris (e.g., disseminated intra vascular coagulo­
H: Multifocal damage Eo Ihe КИЕ farrows) by choroidal
pathy, accelerated hypertension), toxemia of pregnancy
inflnmmalorv cells (coaise black dolsi.
(see Figure 3.59), collagen vascular diseases (Figure 2.14)..
and contusion necrosis of the pigment epithelium (see
Figure £.03). Muorescein angiography typically reveals
mulliple progressively enlarging pinpoint areas of fluo­
rescein leakage at lhe level of the pigment epilhelium and
late staining of lhe sub re Lina! exudate.
There is some experimental as welJ as clinical evidence
to suggest that alteration of the REMi metabolism may be
associated with changes in lhe structure and permeability
of the relinal I capillaries.' 7 Photoirradiation of the KPH
with minimal doses of long-wavelength laser may produce
endothelial proliferative changes in the overlying retjnal
capillary bed.':' Some authors believe that some of the dif­
fuse retinal edema and stain mg of lhe outer retina with
fluorescein in palients with bilateral fmtafoveolar telangi­
ectasis, diabetic retinopathy, Hind tapetoretinal dystrophies
may be caused by alteration of the blood-outer retinal
harrier*
Intraretmal Exudation Caused by
Damage to the External Limiting
Membrane and Decompensation ofthe
Outer Blood-Retinal Barrier
Jlit content and volume of the extracellular compartment
о Г lhe retina thal includes the siibrelinal space are regu-
Ealed by lhe retina! vascular endothelium (blond-inner
retinal harrier} anil R P t (blood-outer relinal barrier).
When there is a serous exudative detach menl caused by a
breakdown in lhe REM: barrier, such as occurs in patients
with idiopalhic central serous chorioretinopathy, the
external limiting membrane (ELM ) of lhe retina prob­
ably serves as a barrier lo movement of sub relinal exudate
into the retina (figure 2.15A). lor this reason we do not
see bio microscopic evidence of cysloid spaces in the outer
retina in these patients. The ELM is nol a true membrane
but is composed of a system of tight junction complexes
uni Ling MiiHer cells lo the photoreceptor inner segment
(zonula adherens). If prolonged retinal detach men L in
these patients causes severe damage lo the relinal -HI.,'vl
Eompte*, however, Earge molecules, including protein and
water lhal accompany them, may accumulate in the extra­
cellular compart menl of the overlying retina, particularly
in the outer plexiform layer. 'I"his results in bio microscopic
and fluorescein angiographic evidence of polycystic reti­
nal edema (Mgure 2.1SB). Initially, lhe dye is derived from
Lhe choroidal circulation, but afler prolonged detachmetn
the relinal capillaries may become damaged and contrib­
ute to lhe leakage of dye into (he extracellular compart­
ment of the reLina. These changes are frequently observed
overlying choroidal hemangiomas [see figures 14.15 and
14.16) and in palienls with retinitis pigmentosa. Extension
of a CNVM into the capillary-free /.one may disrupt the
receptor-lil_M complex and cause cysloid macular edema
(figure 2.L5C). Development of cystoid macular edema is
an hnportanl biomicroscopic sign of subfoveolar extension
of these neovascular networks. The predisposition for this
to occur in the capilLaiy-free zone may be related to struc­
tural weakness of the lil.M where Muller cell processes are
reduced in number as well as to the paucity of retinal ves­
sels there lo provide a pathway of return of the extracellu­
lar fluid to the intravascular comparlmenl.
When the endothelial damage is more severe, large
proteins and lipids escape inlo the extracellular com pa rl-
menl anti Lhe exudate may be cloudy (Figure 2.17). '['he
extravascular protein es transported across the pigment
epithelium, choroid, and sclera. Around the outer margin
of Lhe area of capiltaiy leakage, the transsclerat movement
of protein and return of waler inlo the normal retinal
and choroidal blood vessels by oncotic pressure result in
precipitation of the yellow lipid portion of the exudate
2.15 Barrier effect of relinal external limiting
membrane IELM-R) com pies in preventing migration
of sub retinal exudation into the retina.
A: In tad retinal LL.VI-K complex with no retinal Eidema.
B: LonirslHlldSHg HrtJtlalfyie detachment causing disrup­
tion of ELM-ft CDmpltfs and cysloid гласи I ar cd fm a and
degenenUkjrv
t. : La rly cys-LoSd m a c y jjr c'doma caututi by н-iibfovtal с 1ю-
roida.1 neovasculai m crnbrant1 and disruption of ELM-R
complex.
t>enealh and within the outer retinal layers, where it often
accumulates in a ring-like configuration (ci rein ate exuda­
tion) around the periphery of lhe area of leakage (figure
2.17A). Angiographically, the intraretinal exudation inside
the circinale ring slains wiLb fluorescein. The yellow exu­
date does not (figure 2 .17K- and C). Because ofthe cloudi­
ness of the exudate within Lhe cirdnaLe ring the polycystic
nature of its distribution is less evident biomicroscopicaEly
and angiographically. After resolution of the retinal capil­
lary leakage that occurs either spontaneously or following
pholocoagulalion, macrophages remove the lipid exudate
by phagocytosis (see Chapter 6).
Localized (Disciform} Exudative
Detachment of the Retina Caused by
Damage to the Retinal Endothelial
Blood-Inner Retinal Barrier
['he rale of leakage of exudate from damaged retinal ves­
sels may be sufficiently severe lhal the exudation extends
across Lhe reLinal-Ll.M receptor celL complex into lhe sub-
retinal space. In patients wilh localized retinal vascular
abnormalities (e.g., arterial macroaneuiysm and branch
veiLi occlusion) the secondary relinal detachment is con­
fined to the area immediately surrounding Lhe abnormal­
ity. In patients with a more widespread and severe vascular
abnormality usual к involving the peripheral retina (e.g..
retinal telangiectasis or capillary hemangiomas) chronic
gravitation of the subrelinal lipid-rich exudate lo the mac­
ula and inferior periphery may cause widespread deposits
of the yellow sub retinal and outer relinal exudate remote
from the vascular abnormality. Massive build-up of this
lipid residue is particularly prone to occur in the macular
area, where it may cause severe permanent damage to the
retina as welt as choroidal neovascularization [see figure
6.39A). Angiography in patients wilh relinal detachment
caused by retinal vascular disease shows evidence of intra-
retinal fluorescein leakage in lhe area of the retinal vascu­
lar abnormality and staining of lhe subrelinal fluid in the
vicinity of this abnormality.
Intraretinal Exudation Caused by
Damage to the Blood-fnner Retinal
Barrier
Daraiigf to the relinal vascular endothelium may involve
primarily arteries,, veins, or capillaries or any combination
of lhe three. When it is confined to the arteries or veins...
the exudation is largely restricted to the extracellular space
surrounding these large vessels (e.g., arteritis or phlebitis).
In many diseases the endothelial damage is largely con­
fined lo lhe capillary bed. l'he endothelial decompensa­
tion may he focal or widespread. The severity of capillary
endothelial damage detenuines lhe composition and the
Location of the extracellular fluid. Jf the decompensation
is mi Id only relatively small molecules, including small
proteins, escape into the extracellular space, and clear
serous exudate may be confined lo the in tier retinal layers-
where it is not visible biomicroscopically and is detected
angiographically as diffuse mild staining of the inner rel­
ina. If the capillary damage is moderate, and particularly
if the deeper plexus of capillaries is affected, the serous
fluid spreads posteriorly and laterally where it accumu­
lates within the inner nuclear and outer plexiform layers.
There: the paucity of horizontally coursing interconnect­
ing cell processes permits large polycystic expansion of
the extracellular space, ihe polycystic pattern of exudation
may spread laterally away from the site of the endothelial
2 .16 Aphakic cystoid macular edema.
A l jind A2: Гhorn iid thickening o i Iho CEJOilral macula flssuci-
rilcjd ■with multiple cystoid mSce£ filled w ilh swous oxud^le.
B l , nnd B 2 : Early leakage o f fluorescein idotsf out o i perifo-
vcolar nil inn I capillaries -into sfihjus MUdAte.
C l and (12: Com plete Hlainini; of H U iareliiul exudate t hour
aflor fluorescein iiTjoclion.
decompensation. When the capillaries near lhe center of
the macula are involved, expans ion of the large extracel­
lular space available in lhe outer plexiform layer of ( Eenle
causes the typical hiomicroscopic pi dure of cystoid macu­
lar edema '['here is swelling of the retina and loss of the
fovea I depression caused by development of three or four
large central cysts lhal are surrounded by a series of pro­
gressively smaller cysts [t-'igure 2.16). Angiographically,
fluorescein molecules diffuse out of lhe damaged capil­
laries, slain the extracellular serous exudate, and produce
a stellate pattern of fluorescein staining (t-'igure 2.16).
Compression of Henlers layer that contains a high concen­
tration of xanthophyll pigmenl by the large cystic areas of
serous exudation is probably the cause of the central yel­
low spot seen bio microscopically in the ouler retina as
well as the prominent nonRuorescenl central star figure
seen angiographically (Hgure 2 .]6 C i).
L E S IO N S TH AT O B S C U R E
THE N O R M A L R ET IN A L A N D
C H O R O ID A L F L U O R E S C E N C E
Any lesion that interferes with transmission of either lhe
exciting blue llghl or the emitted yellow-green light w ill
appear either hypo flu orescent nr nonfJuo rescent angio-
graphically. Ef it is located anlerior to the [eve] of lhe
retinal vessels, it will obscure both (he relinal and the
background choroidal fluorescence (figure 2.18].
F L U O R E S C E N C E O F L E S IO N S
U N R E LA T E D T O C H A N G E S IN
V A S C U L A R P E R M E A B IL IT Y ___________
" Pseudoflu о rescent"' Lesions
When angiography is done with poorly matched exciting
and barrier filters, the blue light reflected from the surface
of any white or light-colored non fluorescent. lesion in the
fundus may bypass the barrier filler arid angiographically
appear Lo be fluorescent.
Reflected Fluorescence
Kven when the exciting and biirrier filters are carefully
matched, lighl-coloredr nonfluorescent lesions may exhibit
fluorescence during the late stages of angiography because
of reflect ion from lheir surface of the yellow-green light
generated by the dye that normally escapes into the ocular
media.
Autotluorescent Lesions
Some fundus lesions before the administration of fluores­
cein are capable of emitting yellow-green light when irra­
diated with blue light. Examples of this "auloflLiorescence"
are calcified drusen of the optic nerve head and large
deposits of Jipofusrin
2. 17 Ci rein ate mac ulopalhy caused by congenital
retinal telangreclasis in a 48-year-old man with cysloid
macular edema.
A—С : Note angjagraphi-c evid en ce o i dilated capillaries and
late polycystic pattern oi staining centrally, and absence
Lit staining in Lhe лгедо of lipid exudaLe oulsidu lhe area of
Let^ngieptasfei
D : fcscape (pi protein (Pj and lip id-rich e K u ik le :L I ouL of
damaged relinal vessel into the extracellular currrparlmejiL
ot" lhe reLina and inlo lhe Hubnetinal space. The protein m ol­
ecules чэге transported acros-ь Che choroid and sclem inlo
lhe exl га sclera I space. The w alei component of lhe exudate
is drained inlo the сЬап осар Щ эгЬ and su^rc>uлdin^ normal
relinal vessels. The lipid m olecules precipilale lo Perm yello w
exud-iile (coarse stippling. w ilhiri and EieneaLh the relina in
lhe peripheral urea, w here maximum dohydralion o f lhe esu-
daLe occurs.
2ЩЪ Obstruction or normal choroid at and retinal
fluorescence.
A: O bslruclion ot choroidal fluorescence by subrelinal
hJood.
B: O bslruclion of choroidai <ind retinal (Еиотоысепсе by
blood lying between the internal lim iling membrane o f the
nelina iincl Lhe nerve fiber layer of Ihe retina.
Conclusion
Although for purposes of analysis and instruction the vari­
ous components of the pathologic fluorescein angiogram
have been divided, the reader should recognize that mul­
tiple components often occur together and thal at limes
it may be difficult lo detenuine which component is
dominant. Further. we still have much Lo learn about the
pathophysiology of chorioretinal diseases and some of the
concepts used in angiographic interpretations al this Lime
may prove lo be wrong. Nevertheless, these guidelines
should assist readers as they explore other sections Ln this
book and as they begin lo interpret angiograms of lheir
patients.
 Lilians VIis^kj^fr РЙтп^йЬШ^У

2 ; 1 ft
]N D O C Y A N IN E G R EEN
A N G IO G R A P H Y
ICG Is a water-soluble tricarbocvanine dye with both
hydrophilic and lipophilic characteristics. Et absorbs light
in the near-infrared range of 790-805 nm. it tin its light
Lii the 770-8Д0-nm range wiLh peak emission at 835 nm.
ihe RPE And choroid absorb 60-75^o of lhe blue green
light used in fluorescein angiography (500п т ), and only
20-3fl% of lhe near infrared light (800 nmj used in ICG
angiography; he nee ICC ran be used lo visualize structures
under the RPE.J
ICC is У8% protein-bound, mostly to globulins such as
alpha-lipoproteins, hence less of Lhe dye escapes through
the feneslralions of the choriocapillaris, thus allowing
for imaging the choroidal vessels, unlike fluorescein (hat
rapidly escapes into lhe extravascular space, preventing
delineation of the choroidal anatomy. N I fbwewer, some
amount of ICC slowly dilfuses through Lhe choroidal ves­
sels, staining the choroidal stroma in about 12 minutes.
Images should be captured up to 30 minutes during the
study. 1 L'he digital imAging system has an excitation fil­
ter that allows passage of only near-in fra red light which
excites the ICC molecule and the emitted light is captured
via a barrier filter Lhat blocks wavelength below 325 nm,
thus capturing only light emitted from the excited ICC
dye. Keal-lime. wide-angle, digital subtraction, and high­
speed angiography using scanning laser ophthalmoscope
are all possible.
ICC con tains a small amount of iodine and has to be
used with caution in patients with iodine allergy. Nausea,
vomiting, and urticaria are less common than with fluores­
cein. ICC comes packaged as a 25-rag dry powder and is
reconstituted with 5ml sterile water.
Principles of Interpretation of 3CG
Angiography
I'luorescein angiography is still the mainstay in the evalua­
tion of most relinal and chorioretinal disorders. ICC angi­
ography has a role in certain conditions. With presently
available technology and knowledge, ICG angiography can
be specific for: (1) identification of polypoidal choroidal
vasculopaLhy; (2) occult choroidal neovascularization;
(3) neovascularization associated with pigment epithelial
detachments; and [4] recurrent CN'VMs. ICG angiogra­
phy has a clear edge over fluorescein in delineating these
lesions. [CG has some role as a guide in diagnosis or treat­
ment - in identifying feeder vessels in age-related macular
2.19 Indocyanine green (ICG} angiography.
A-E: Left fundus of a 32-year-old African Am erican Wom an
w ilh bilateral polvpoidal choroidal tascu^opalhy .Ai. Note
lhe orange nodules in Lhe iLixLapapiliary relina and lem ро­
га] fovea (amoMra). A small jujdaujveal disciforno is seen.
Midffames al' Lhe fluorescein лп^ю ^глт and iC G d elin ­
eate Lhe polyps ■ :B—fJj. Auto fluorescence ima^in^ i.E.i shows
decieased a uLo fluorescence and lhe lluonescein ап^зодгат
shows a transmission detec I corresponding Lo 1he fovea I scar.
The o u lIinet of the polyps are visible on aulfif I uqi]p5oencR
imayin^.
F-L: А ^-year-old won«m with serous deLachmenl of the
macula iFl. Early FC.'tl shows lhe individual chorojdal ves­
sels and lhe laLe frames a hot spot or slain injj at lhe nasal
edj^e (-G—I). The fluorescein angic^ram also shows sLainini^ of
lhe same region thouj^h Ihe staining pattern in Ihe I w o dil'lcr
11 and K). The lesion seen on the fluorescein an^io^ram a n d
IC C shows decreased ^utofluorescence; how evei lhe pnoleln-
aceous ibih in the macuia shows hvper auto fluorescence ■:!. ■
.
degeneration. CNVMs, chronic central serous retinopathy
multiple evanescent white-dol syndrome, acute multifocal
placoid pigment epilheliopathy, Vogt-Koyanagi-Elarada
зупфготе, macular lesions associated with angioid streaks,
and bindshot chorioretinopathy, Huorescein angiogra­
phy is sufficient in most of these conditions Lo make the
diagnosis; ECC helps to corroborate some additional
evidence.^'
Schematic interpretations are similar lo fluorescein
angiography with hyperfluorescence and hypo fluorescence
relative to the surrounding area of presumed normal flu­
orescence (Figure 2.1^}. Elypofluorescence can be from
blocked fluorescence by thick blood or melanin pigmenl.
or due Lo vascular filling defect. Similar lo fluorescein
angiography, (he study has to be interpreLed by reviewing
images at various time points, since some areas that are
initially hypofluorescenl may turn hyperfluorescent late,
such as plaque staining in occult CNVM [figure 2.1УС-
]J, and chronic central serous chorioretinopathy in oth­
ers, hyperfluorescence seen in the early frames may turn
iso- or bypofluorescent late in Lhe study, as in "washout”
phenomenon of choroidal hemangioma. Pooling of [CG
dye can be seen in the late frames of serous ВДЕ detach­
ments. In addition certain anatomic changes in the choroi­
dal vessels can be seen such as polypoidal vessels (E'igure
2.19C and D) and feeder vessel(sj of a CN'VM on high­
speed angiography. Areas of occluded or missing choroidal
vessels can be seen in arteritic ischemic optic neuropa­
thy. Individual examples are described as and when they
appear in various chapters in the text.
fHdtH'i/nniiif Сп’ш 49
A U TO FLU O RESC EN C E
Lipofuscin is a pigment that auto fluoresces when excited
by blue light or an ultraviolet itghl. Jhc R P t accumulates
[ipofusem and melanolipofuscin over time and this gives a
background autofluorescence to the retina.' Jl' In certain
disease slates the ли to fluorescence increases or decreases-
and ihis can be imaged by aulofiuorescence imaging.
The Eleidelberg machine uses а 4ЙД-пт exciting and
barrier tiller for capturing autofl uoresce nee. Elowever, lhe
lopcon uses 512nm for ex.eiLing and 488 nm for capturing
the aulofluorescence. ]n addition to lhe lipofuscin, A2H
and alher producls can also exhibit autofluorescence/123
One has lo remember lhal aulofluorescence is masked by
increasing nuclear sclerosis of the lens. 'Ibe lens absorbs
some of the blue-wavelength light, which decreases
both the excitation of lhe aulofiuorescing material at
the pigment epithelial level and capture of the return
aulofluorescence.
Uolh the scanning laser ophthalmoscope and a video
Lund us camera can be used for cap Luring aulofluorescence
images. Ihe fluorophores other than lipofuscin and A2L
are iso-A 2E;, А2-РЫ12, А21Ч:, and A2-rhodopsin, all of
which are precursors of A2t, and which are formed in the
outer segments prior lo phagocytosis by Lhe Rl1!-..'-' ■'1'Jl'
Lipofuscin fluorescence has a broader emission band rang­
ing from 400 to 750 п т , hence the video fundus camera,
which has ex.ciLilian filter al 550 nm. picks up more aulo-
Lluorescence lhan the ] ieidelberg scanning laser ophthal­
moscope, which uses a 4S8-nm excitation niter.
Common conditions that show increased auto fluores­
ce nee are flecks of Slargardl's disease/fundus fiavimaculatus
where the Rl-’t; cells are not atrophic (Figure 2.20] and I),
RPE surrounding areas of alrophy (E'igure 2.20), RE1Г sur­
rounding the areas of pbotoreceplor disruption such as in
cone dystrophy, adjacent lo areas of alrophy in maculopa-
tby associated with mitochondrial mutalions and tbevilel-
Eiform material in patlern dyslrophy [figure 2.20C and
Dj and best disease (E'Lgure 2.201: acid }:). Other examples
of increased aulofluorescence are patients who have had
resolution of uveal effusion where lhe highly protein-
aceous material is being reabsorbed by the RPk and is
2.20 .Autofluorescence.
A Hind №■: Koi-t scIoral windows in a pationl vvilli idiop,ilhac
иуедГ effusion shows resolution o f lh e 5HF with plump reti­
nal pigmenl epil helium fEiF'L' cell> filled w ilh absorbed
protein and reorganisation lipofuscin лn-rl ftmaceEtuialf
pigfnent shows increased autoflUbrescencei
С And D: Focal increased aulofluorescence corresponding to
Lhe vi Lei I iform change in this patient with solitary viteFliform
pa Item dystrophy or aduit-onsel foveojnacular dystrophy.
E and F: A fi-year-oJd girl with L3esl disease shows iiiLenHe
hypef^Lnflgorescenpeaaf:ht? vilelliform d&tachmenL
G and H: Ova] Ljli 11 change in the matUjlia in Lhis
52-year-oEd wom an wiLh cbloroquine toxicity shows
decr^^SM aulofluorescence due I о disruplion of KHt cells.
I and |i This 40-year-old man w ilh SLargardl's disease iand
fundus flavimaculatus shows increased aUtuflilorespence
corresponding Lo Lhe ye llo w flecks and decreased auLotluo-
rescence Gqffltspdtidina to lhe areas of RKL atrophy and loss.
К and L: Aulofluorescence imaging clearly shows Lhe dis­
tinct margins of chorioretinal atrophic patches that are noL
as discernible on Lhe color photograph in this 5 fi-year-oId
wom an w Hi probable non-Ji-linked chofoidtrem ia. N o le the
flecks of increased auto fluorescence in Lhe intervening zones
suggesting uptake of excess lipofuscin by lh e surviving KPE
ceils.
loaded with this fluorophore (E:igure 2.20A and >S) (see
Chapter 3).
AutofluoFescence imaging is especially useful when Lhere
is decreased auto fluoresce nee in areas of IUnJL loss. This is
of benefit in patients wilh geographic atrophy (E'tgure 2.20]
and L) where the contrast on autofluoresoence imaging is
more distinct compared Lo color fundus photographs and
helps in accurately monitoring for progression, especially
in age-related macular degeneration and Staigardl's disease.
Another good example is in patients with chronic centra]
serous chorioretinopathy and MEiWDS where the sublle
RE3Ei alteration may not be easily visible on a fundus photo­
graph {Figures 3.06, 3.07 and 11.15, 11.16). Several exam­
ples are described in the various chapters.
■
O P T IC A L C O H E R E N C E
TO M O G RAPH Y
Ocular coherence tOmogijiphy JG C T J measures the echo
time delay and Intensity of back-reflected or hack-scattered
Eighl. ]l provides real-time high-resolution cross-sectional
images of the eye, and this enables identification of mor­
phological alterations, and provides contour information
and thickness measurements, its principle is similar lo
ultrasound, except that it uses light instead of sound. Low-
coherence interferometry is the principle on which OCE'
measurements are based.-5'
lhe interferometer has an 800-nm laser light source..
which is projected on lo a beam splitter (partially reflecting
mirror) Lhal splits the light into two paths, one that is trans­
mitted inlo the eye and the olher lhal is reflected. The lighl
that is transmitted inlo the eye is reflected back lo lhe beam
splitler from various intraocular structures as multiple
echoes based on lheir distance and thickness. The second
beam is reflected from a reference mimor placed at a known
spatial position back lo the beam splitter where il combines
with the beam reflected from the intraocular structures, lhe
Eliterferameter can precisely interpret the echo structure of
the reflected lighl lo make high-resolution measurements
of distance and thickness of the various structures, ihe OCE
allows:
1. imaging of retinal and choroidal layers [I igure 2.2] A-H)
2. retinal diickness measurements
3. retinal topography, mapping and analysis
4. retina] nerve fiber layer thickness measurements
5. retina] nerve fiber layer analysis
6. optic nerve head i magi tig and analysis
7. enhanced depth imaging of the choroid [Eletdeihurg
Spectralis ОС]').
Two principles of О С Г imaging are currently used -
time domain and speclral domain. Spectral domain
ffiDr^LO/OCT) uses ja S40-nni diode lighl source and per­
forms a sweep of 236 serial paraElel OCT E>-scans with an
axial resolution of З ц т , covering a 9 X 5-mm area iti the
transverse plane through the macula. Time domain stra­
tus О С Г (Stratus OC£ version 4.0.1 r Carl Zeiss Meditec
Dublin, С A, LISA) uses an 810-nm wavelength diode
source and scans six consecutive radial Б scans with a
resolution of lOjjm. Spectral domain has several advan­
tages over time domain imaging in that il has a faster
2.2 [ Op tical to heren ce Lomogra plhy (OCT J.
A and B: Swollen disc wilh dilated vessels on ils surface
with macuLir s-laг in a patient with сдI-scratch disease. OCT
shuwb turbid sutjrelinal fluid and inlra netina I Iif]id in the
oukir plexiform layer IrmuwHl.
(.. and D: Bull's-еун гласи lopalhy in a parent with chltMO-
quine toxicity. Corresponding OCT shows disruption of photo­
receptors Lind loss ot inner segment/outer segment (lap s)
junction in the fovea.
E and F: Client wilh Uascul^i^d retinal pigmefit t>pi Ihelium
iKI’tl detachment secondary lo occuEt choroidal neovascular­
ization in the ri^ht eye. 5lrah_S| iLinie>domainl OCT kHows the
eleimfed RPE and adjacent subretinal Eluid (5KFJ (artifcrtV).
acquisition speed (30 times faster, thereby decreasing
motion artifacts from eye movements), scans a Larger area,
has hEgher resolution, and can reproduce the same point
of reference each time.
U L T R A S O N O G R A P H Y ________________
Ultrasound uses acoustic waves lhal are created from oscil­
lation of particles within a medium. LHlrasoutid waves
have a frequency greater than 2QOGO oscillations per sec­
ond or 2t)klEz, rendering them inaudible to humans. Ihe
frequencies used in optilhalmic ultrasound range from &
lo ffiM l tz for conventional A and li scan. 'Ehe higher the
frequency the shorter the depth of penetration An ultra­
sound biomicroscope uses a SO-MHz prober hence the
depth of penetration is low and limited I о Lhe anterior
segment. The velocity of the wave is dependent on the
medium through which it passes; hence the wave passing
through water, vitreous, silicone oil. or a solid mass has
different speeds, 'ihe more compressible the medium the
slower the propagation, thus the sound waves move faster
in a solid tumor than the liquid vitreous. Acoustic inter­
faces created at lhe |unction of two media have different
acoustic impedance. Ihe angle of incidence of the sound
beating against an interface is important in determining
the strengLh of the returning echo. In addition, the size,
shape, and smootbtiess of the interface play a role in the
character of the returning echo. Some of the ultrasound
is absorbed and converted lo heat as it passes through a
medium; however, this is extremely Low and has no harm­
ful effects on tissue.
 IWcj American ophthalmologists, t>rs. Murick and Hughey
evaluated an intraocular lumor by using an amplitude mode
(Л-scan) ultrasound for the first time in ophthalmology in
1У56.1:1 In 1958 Eiaum and Greenwood developed the first
Lwo-dimen&ional immersion brightness mode (ЕЗ-scan) ultra­
sonogram for ophthalmology.11 Coleman and Weininger-
in the late 1960s., developed Lie firsl commercial immersion
11-scan ophthalmic instrument.'1 A contact tf-scan machine
was introduced by Bronson.1 ''
Instrument and Technique
Jhe transducer probe is the structure lhal products the
echo. Л piece of lhe electro crystal is placed near lhe
face of the probe and undergoes mechanical vibra-
Lion when it iinula ted by electrical energy. 'Ihis vibration
causes a longitudinal ultrasound wave that is propagated
through any medium. Certain terms need to be defined
and understood in order to perform and interpret ocular
ultrasonography.
Cain
All ultrasound instruments are created to adjust lhe ampli­
fication of the echo signals. Gain is measured in decibels
and represents the relative units of ulLrasound intensity.
Adjusting the gain does not change the aniou.nl of energy
emitted from lhe transducer; however, it changes the inten­
sity of the returning echo that is displayed on the screen.
Ihe higher the gain, the greater the ability of the instru­
ment to display weaker echoes., e.g.. vitreous opacities.
Clonverselv, if the gain is Lowered only strong echoes of the
retina are displayed, and thus eliminating low-jnlensity
echoes from vitreous hemorrhage and of her opacities, if
present.
Shadowing
When the sound beam interfaces with solid tissue a signifi­
cant portion of the echo of the beam is reflected back and
only a small amount is transmitted. Ihis creates a shadow
behind the solid interface. Shadowing is prominent when
sound waves interface with high-density substances such
as calcium or bone.
Dampening
When the sound waves interface with a solid mass, some
of the echoes are dampened, and this is especially seen in
choroidal melanoma, where the reflected echoes drop in
intensity as the wave passes through the lumor.
Important steps in performing a good ultrasound
В-scan are based on the following.
T h e В-Scan Probe Orientation
ihe basic oriental ions are axial, longitudinal, and trans­
verse. 'lhe ultrasound probe has a mark at the Щ o'clock
2.2 E Continued
Ultrasonography fUSG).
Ct : Nurmal mjlraSOund В 5dart Ы the ponUirior sc^menl. The
Optic nerve is normally: ecjho-luc:enl.
H —|: A patient with choroidal hemangioma showing an
orange eEevalton. The В scan shows a solid mass w ilh
smooth contour. А scan through the т я ;;* shdwS hiyh inLer-
HliI reflecLitily.
К and L: A patient w ith a retinal detachmerrt on В scan iK:
iirrd л single bpike on ап А ьелп that denotes lhe detached
relina :L'l.
hour which signifies the superior pole of the displayed
image. Turning this line lo a specific clock hour allows
images lo be seen in an axial orientation in that clock
hour. When evaluating an intraocular lesion, lhe follow­
ing components are evaluated: the location, extent, shape,
reflectivity, internal structure and attenuation, after move­
ment 4rascularity and convection movement.
Reflectivity
Jiefleclivily measures the reflectivity of all detected lesions.
Depending on the number of interfaces present within the
lesion, the reflectivity is altered. I hose that have multiple
interfaces such as a choroidal hemangioma display high
internal reflectivity (E-'igure 2.21 H-|). A solid mass such
as a choroidal melanoma decreases the internal reflectiv­
ity as the sound waves pass through the compact lesion.
Much more solid structures such as choroidal osteoma or
a metallic foreign body will cause shadowing by prevent­
ing transmission of most of the sound waves through lhe
solid structure
An ultrasound E>-scan is invaluable in evaluating fea-
lures of choroidal tumors, choroidal osteoma, or a retinal
detachment (i'igure 2.23K and L) when associated with
media opacities such as cataract or a vitreous hemorrhage,
ll is also invaluable in determining the presence of. or
locating, a retina! tear in patients presenting with a dense
vitreous hemorrhage. It is useful in locating an intraocu­
lar foreign body if associated With a vitreous hemorrhage
that obscures fundus details. The start of. or presence of,
a posterior vitreous separation can be seen in palients
wilh traumatic vitreous hemorrhage to help time surgi­
cal intervention. Presence of a dislocated intraocular fens
can be confirmed in eyes wilh trauma. A choroidal effu­
sion in a postoperative glaucoma eye can be evaluated and
monitored. E.iquefaclion of blood in suprachoroidal hem­
orrhage a few days after the event is useful in liming lhe
draining of the suprachoroidal blood. Choroidal thicken­
ing can be evaluated in patients wilh uveal effusion and
choroidal inflammation such as Vogt-Koyanagi-E!arada
syndrome and sympathetic ophthalmia, l'he presence of
any mass in and around the ciliary body can be evaluated.
i I L l~ - l □ [ F ] - £ . 0 hi
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TS ■ 64dB
A D A P T IV E O P T IC S
bcannmg Eiir^er ophthalmoscope л] tows microscopic view­
ing of living tissue, lhe system has to overcome several
aberrations beginning from the ffcar film, cornea, refrac­
tive indices of lhe lens and other structures aitd various
accommodative status of the eye to be able Lo obtain a
clear image of the retinal structures. Babcock. Elubin
and Goethe/' and Liang et a L lK used adaptive optics Lo
compensate for the monochromatic aberrations of the
eye. AOSLO is a scanning laser ophthalmoscope that uses
adaptive op Lies lo measure and correct the high-order
aberrations of the human eye. Adaptive optics increases
both laLeral and axial resolution, permitting axial sec­
tioning of retinal tissue in vivo. ГЬе instrument is used to
visualize photoreceptors, nerve fibers, and movement of
cells through retinal capillaries.'1 She central lO - lZ 5 of
cone mosaic can be imaged in the fovea/"' and combin­
ing it with images obtained using high-resolution spectral
domain О С Г may be helpful in detecting photoreceptor
changes, and their loss over Lime in understanding pro­
gressive macular dystrophies.1:
E L E C T R O R E T I N O G R A M (ER G )
lh e KRC is an electrical potential generated by the retina
in response to a flash of light. A standard ERG testing
done in the clinic measures: ( ] ) the ir.RC lo weak flash
or 24-dK finish, performed in scotopic or dark-adapted
conditions that measure lhe rod pholoreccplor poten­
tial; [2] followed by a very slrong flash, 0dB in the dark-
adapted state, which measures combined rod and cone
function; (5) the oscillatory potentials are next recorded;
(4) the patient is light-adapted for approximate-ly 10 min­
utes followed by tLRC wilh a slrong flash Odb to measure
the polential arising from the cones; and [5) repeated
stimulus - .1011z flicker is used to stimulate repeatedly
the cones lo pick up photopic responses lo superslimula-
Lion. Specialized types of ERG include: multifocal ERG
(mfV.RG), focaE ERG, and pattern ERG.
Technique
Jhe patient is asked to sit in front of a Ganzfeld bowl.
Contact lenses are placed over both corneas and a ground
electrode is placed over the ears, lhe patient is dark-
adapted for 20-30 minutes prior to testing in usual cases,
longer dark adaptation is used in certain situations such
as in stationary night blindness, in lhe dark-adapted State
a 24-dB photopic Hash or a blue lighl is used; this is a
weak flash that stimulates the rods (figure 2.22A and F),
The origin of lhe a-wave is mainly associated with
photoreceptors but also has a postreceptor contribution
primarily from the relinal off pathway. The dark-adapted
2.22 E!e сtroreti nogram (ERG),
A—E: Normal EhtC recordings in a 65-yeaг-ofd wum an. In the1
□aif'к-adapted stalE л dim fl n-sb '.24dbj slimy bless lhe* rods and
is measured as a b w ave (A). A stronger Hash (0 dbv in the
dark-ddSbted i-Lale HtmiulaLu* both the rods and to n es gen­
eral inj^ larger a ■
'fi rs;L rregative) and b I firsl m&srtive) waves ! В :.
The oscillatory potentials \OFiil are recorded next (Cl. In а
lijjht-adap-k'd Slate л kJ rcjni’ flash (OtJb stim u late only lhe
cones Ljfneratinji Ijoth a and b waves It.l:. Conlinuous sLimu-
lalLun of Ihe с о ties by a 30-Hz flicker liyhl results in several
negative and positive waves; o nly the b wave am plitude is
measured and inlejpfeled iL .
F-K: A i4-year-old wtnnun w ilh rapidly eniar^in^ Lctmpo-
raf field defed associated with photopsias in her left eye
was diagnosed with acuLt1 гопад occult outer reflmopalhy
lA Z O O K i. Ал LRC1 shtsws isyj rifi lyftV between the two eyes
buth in nod and cone function (F—I). The riqht fundus is normal
[I), the lell shows peripapillary retinal pigmenL epithelium alro­
phy eo:respondin^ Lo lhe efctenl of lhe enlarged blind sfiol (K..
TIk ! left еуе'н LbiC ampliLudes are lower than the ri^hL due lo
loss or dysfunction of lhe peripapillary pholuaetepLore.
a-wave is lhe initial negative wave lhal occurs in response
lo the strong stimulus. Lhis is only seen when both rod
and cone functions are lesled (Figure 2.22b and G). The
a-wave from cones alone occurs in Lhe light-adapted state
using a slrong stimulus. 'L'he b-wave es generated when the
conduction of the receptor potential occurs from the pho­
toreceptor onwards through the inner relina. 'L'he b-wave is
contribuled by the depolarizing activity of the bipolar cells
(Eigure 2.22K and G]. Hat Lents who have some amount
of cone dysfunction may show adequate amplitude on
the single flash photopic recording {figure 2.2ILL? and
IE). Howevet on repeated stimulation { l:igure 2.22E and
J), the amplitudes may fall off. The b-wave is a positive
deflection at light offset that is characteristic of photopic
l:3tC. Special cases of electro negative b-wave in patients
with congenital stationary night blindness are due to the
poor onward conduction of the receptor potential gener­
ated at the photoreceptors.
'lhe oscillatory potentials are a series of high-frequency
low-amplilude wavelength superimposed on the h-wave
lhat occur in response to slrong st ini ulus. 'Jhese are pres­
ent in the lighl- and dark-adapted conditions wilh con­
tribution from both rod (figure 2.22CJ and cone signals.
The number of oscillatory potentials induced by one flash
of light ranges between four and 10.
lhe oscillatory potentials are generated due to neuronal
interactions and feedback circles and lo intrinsic mem­
brane properties of amacrine cells.
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M U L T IF O C A L ERG
lhe mfHKG provides ni topographic measure с Г relinal elec-
Lro physiological fu n c tio n .Il is es pen ally useful in condi­
tions such as cone dystrophy and olher disorders affecting
Lhe po&lerior pole. Since there are a number of lighl stim­
uli lo several areas of lhe macula in a rapid sequence, the
eye is rendered vlighL-adapled,n and hence only cone func­
tion can be Lested.1'1[t measures app гоя in] лLely 40 0 of lhe
central retina. Severn] small potentials, typically 61 or 103
(wide field), at individual sites approximately 3-53 apari
are recorded from cone-driven retina.
As in full-field conventional ERG recording a corneal
electrode is used: however the nature of the stimulus and
the form of lhe analysts differ, lhe retina is stimulated
with an array of hexagonal elements (either calhode ray
tube (СЙГ) or Eiquid crystal display (LCD ) technology),
each of which has a 50% chance of being illuminated
every lime the frame changes (Figure 2.23 A). Each element
follows the same pseudorandom sequence of illumination
with the starting point displaced in Lime relative Lo other
elements. The recordings are not direct electrical potentials
from local regions of relinar but rather л mathematical
extraction of the sign al.'15 Because lhe stimulation rale is
rapid, the waveform of the local mfliRG response can be
influenced bolh by preceding ("adaptation effects") and
subsequent stimuli ("induced effects"), as well as by the
responses to lighl scattered on other retinal areas.'1'1
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2.23 Mu Eli focal eleclroreti nogram imt'EKG).
A: 6 ] hexagonal elements slimulale [tie c:enlr,iJ noli пл.
В D: Trace array showing normal retinal response in tliE
Hi mutated л гея.
Cr E: Three-dimensionat lopayraphy showing normal fuvt'Jil
and eslrafoveal response.
F Lind C: Ан/егд^е mftUG amplitudes of lhe various zones
int'a^Ljred at (nolaled by ihyculors;! Ml And НГ.
Electro-oculogram (E G O ,
H : Normal E O C measurements o f the right and lefl eye:
1, dark Lrouf^h And 2; chu li^hl peak. Arden rAliu is Ihe dif-
Гегипие in AmpliLude between tfi£ lijjht ptwk Lind lhe d^rk
LrDLigh.
lhe typical waveform of the basic mfEKG response
(also called the first-order response от first-order kernel)
is a btphasic wave wilh an initial negative deflection fol­
lowed by a positive peak {Hguie 2.23Й, D, h and G). There
is usually a second negative defleclion after the positive
peak. 'Ihese three peaks are called N I, P I, and N2, respec­
tively. N1 includes conlri but ions from the same cells thal
contribule lo lhe a-wave of the full-field cone LK£], and P I
includes contributions from the cells contributing to the
cone b-wave and oscillatory potentials. Although lEiere is
some homology between the mftiUC waveform and the
conventional Г KG, (he stimulation rales are higher for
the mftiKG and, as noted above, the infllRG responses are
mathematical extractions. Thus, the mft-RC responses are
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not technically ‘'little LKG responses." therefore, the desig­
nations fa-wave' and "b-wave. ^ used for the full-field ERG,
are not appropriate to describe features of the mfEEtG
wave form.46
Technique
The pupils should be dilated and pupil size noted,
fixation sLability is important and can affect the qual­
ity of recordings and can be monitored. Refractive errors
may niller the area of the retina stimulated due lo diffrac­
tion of the Eight stimuli; hence refractive errors should be
corrected. Pneadaptation involves exposing the subject lo
ordinary room light for al least 15 minutes prior to test­
ing. Moderate room lighting close to the illumination on
Lhe stimulus screen should be used. A total recording time
of 4 minutes for the (SI stimuli and & minutes for the 10.1
stimuli is required.
The responses are displayed as trace arrays (wave forms)
(Figure 2,23В and D ) and three-dimensional response
density plots (Figure 2.23G and Lj. '['race arrays are useful
in comparing an area of low amplitude to another area in
the same eye or a corresponding area in the fellow eye.'1
It can be compared against similar quadrants on a visual
field.1" Ihe three-dimensional plot shows the overall sig­
nal strength per unit area of the relina. Jhis should be
interpreted in conjunction with the trace arrays and not by
itself.
E L E C T R O - O C U L O G R A M {E O G )
When an electrode es placed oil lhe cornea and another
near die posterior pole of the eye (or elsewhere in the
body), a positive resting potential is found.4^™ 'Ibe EDG
displays this corneofundal potential, which benders the cor­
nea 0.006-0.LI]ОV positive compared to the posterior wall
structures (retinal receptors and RE’Ei) of the eye. Ihe cor-
neofundal potential is the result of metabolic activity of the
epithelium of the cornea, lens, and retina, ihe potential
from the RE3E is photosensitive white that from the cornea
and lens epithelium is dot. lhe RPE loses the potential in
the dark and recharges during light adaptation, '['his dif­
ference in lhe potential between dark and light, called the
'light peak/ is termed Arden ratio (Figure 2.231 {).
The measurement is based on the eye mcjvemenl-
dependent voltage generated and recorded between elec­
trodes placed at the inner and ouLer canthi of the eye.
Ihe palienl is seated in fronL of the Ganzfield bowl and
asked to look back and forth between two fixation lights
placed 50° from each other. When the eye moves to the
right the positive cornea becomes closer to one of the elec­
trodes, ihus rendering this electrode more positive than
the other, and the opposite occurs when the eye moves
Lo the left. 'Jhe palienl is preadapted in room light for 15
minutes. Fifteen minutes of the recording occurs in the
dark, followed by 20-minute recording under standard
light adaptation using the Ganzfaeld bowl. 'Ibe test can be
performed with the patient dilated or not. if the patient
is dilated the intensity of the Ganzfield background lighf
should be lower than if not dilated. The dark-adapted
EOG reaches a minimum and then fluctuates. L'he light-
adapted FOG gradually increases and reaches a maximum
and dien drops gradually. 'Ehe Arden ratio is the differ­
ence in the amplitude between the "light peak" and the
"dark trough'1and the normal is at least l.S, often around
2.5 (Figure 2.231-]). ihe right and left eyes are recorded
simultaneously.
'Jbe EO G is a function of the entire ]?I^Ei—photoreceptor
complex and not just the macular and photorecep­
tors. Rod and cone mechanisms contribute to the gen­
eration of the potential.П| EOG is abnormal whenever the
ERG is abnormal but the reverse is not true, as in Eiest dis­
ease and chloroquine toxicity.
In conclusion, a given patient sbouEd receive the
necessary and appropriate studies for diagnosis and
re-evaluation of treatment response. Ibe principles and
interp relation of fluorescein angiography have received the
most attention in this chapter. Understanding fluorescein
angiography should help the reader interpret oLher stud­
ies such as ICG angiography, aulofluorescence, and O CF
Only the basic principles of the remaining studies have
been touched upon, lo assist the reader in quickly inter­
preting their results. For a more succinct understanding of
the individual studies, lhe reader is directed to more elab­
orate sources.
References
1. Ocfltt SMG. F ft S_ MJin ; IF; a al.Traiaenl n за iilrg atef towtor red m 1
р1кйювм1ё(п1Ьг(Знсш пвтажиЕапгетЕвапк Fulra lEftioSfc-SC.
2. JtistiffiJrl Serajsdetadimfftot Etteredral вдпн! epftsi.ri
T r m d ir fe a d О з П П а ™ '9ве.7-ЗтЭ9С— 015.
Btdskn з! i u r a e a 'r s M H : j a 1 т т Ь т а л к . Д п J Oaitia rrcr' .£04:11 3 :2 6 ^ 3 ' '
i Gjj'j DR FMslte W, M ira M a al D:]ral ntaraine а ч щ cpxty in сЕюгаага!
а&>-З Е!з.сс1ш £1ж ^у аи2г?э:ае7-э1.
1. КМкгWrt Nc>]i; Cf!. & li es RA. ?. al \ pemeaMto JclKl c!retin al j.-gmiri sDrlhciF.il1
k e j 'етсе n fliu siepteiacr entiles Arch Sftttiamai' 9 Ю £ Й :72 Е-6
6. Ma'tfa I Qiwef * FeIIbn in e n?,v; ndm si ransi hBiatm зу krvш 1 . эг-с
1ж(5. Gx Opitalrfll Fl х Евг1 -if.
7. T s o k lC H CUiha-№z JGF.-Stih m al/AjcirnDDpaftnfci^o s u ly ut sbod-r^iii^ hanler№
й>ргг ir-ETal o i f l l s i , AfWD n t t : СрМтаПкЕ «1; £c 1 & ? i:l3 :l Ё5,
2. Caasfcall AG. CEiane G. ^lusti F. a al Faintic.la' le a.idKlaitf. Trait CthiialncJ Soc E#
1 9 f f i ;1 0 5 $ & - &
5. F c-ra ftV. Нж1п;:ткг Br ЕффалЕе gten ays; иэгьакше n t ririrec Лккрпол
L ta d a ^ a n g ai arn иЯапюиф w t i HitDreacefl apograph* Jcfin; H c ^ i ;
ll Craig W.Marae L3, raida F. id^.HHHKElKalisiha'cl rdx^inne wsn J/eiiagre
anmiifi an humn oailarSisaiesMPiefncd алжшрЕнс антеЙнп Оз№а(г^сдгг
i £08105:1 Gft-S
ll om DH. ?zin Ftrtsf Ш FttcTa сnalqiptsUionEal рй>^пnegran■Sa'aca
- crelmnirv i s t r t E- e Ear toes T h 'a i f/m l ^ : E :E ? .' ь-2 3 . o i |
12. F ■w FJV HKhiei^r Br dp;al s сиarc азрагаШ; Id' areJlaieci; 7
liie safaralt Binsl ac (hmeidal с г л й м г й . ItmsE Ofhi'dio]! 1&73:' 22^3-£l.
1 3. fe e r a ^ i te r> :A Сем i f s-Hral d a ails :si C; a; retiHfd Памгсй h m lais-; ar.:i
anerldil зшгьза AmJOptotelmal 1Э6Й66:15-И}.
14. Eater E^J. E r d r q c liu lc i'c io D fh te n ^ F l K d t m l i a h fo q a riifi iC 3 tw o ton a
a p t & ■ Ip p it e h s . FTac Е е M № d ■966:122:557-63.
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This page mtentlonaSly left blank
 Diseases Causing Exudative and Hemorrhagic
Detachment of the Choroid, Retina and Retinal
Pigment Epithelium
Diseases primarily involving the choroid cause loss of reti­
nal function in the macular region principally by three
mechanisms: ( ] ] reduction of blood flaw within Lhe cho­
riocapi Haris; [2) increased permeability of lhe choriocapil-
larib causing exudative and hemorrhagic detachment of the
retinal pigment epithelium (RPE) and/or retin® anti (3J a
coLTibinalion of lhe Iwo processes. E>iffusion of nutrients
from the choriocapil laris across Bruch's membrane is Lhe
major source of sustenance for the RPE and lhe photorecep­
tors. r['he choriocapiIIary endothelium and the RPE are the
primary barrier to the passage of large proteins and oncotic
water from the choriocapi Ilaris inlo the sub relinal space,
interference with the blood supply to the choriocapi 11 ris, for
whatever reason, may lead lo lhe loss of function of the over­
lying RIM- and retina. Acute visual loss secondary to obstruc­
tion of the short ciliary arteries occurs infrequently because
of the rich arterial anastomosis in the choroidal vascular bed.
Acute visual loss may occur, however, from either embolic or
Lhrombotic disease obstructing the choriocapi Ilaris. Ihere is
minimal evidence that chronic ischemia secondary to grad­
ual obi iteration of the1lar^e and small choroidal vessels is a
significant cause of deterioration of central vision, loss of
central vision occurs most frequently because of serous and
hemorrhage macular detachment caused by a variety of dis­
eases afTecLing the choriocapil laris, Bruch's membrane, and
RPR ihe frequent circular shape of this detachment or the
scar that results is responsible for use of the descriptive terms
vdisciform detachment* and "disciform lesions.''' Although
most localized detachments of the macula are caused by
diseases affect mg Lhe choroid and RPE:,. a localized macular
detachment may occasionally be caused by relinal vascu­
lar diseases, by retinal hole, by vilreomacular traction, or by
anomalies of the optic disc (see Chapters G, 7, and 15).
The peculiar structure of the choroidal vascular system
is probably of primary significance in explaining the pre­
dilection for localized detachment of the RPE and retina
to occur in die macula and peripapillary region of the eye
(see chapter I). It is in ihese areas that a large volume of
blood is fed inlo the choroidal circulation by way of the
short ciliary arteries (see figure 1.(16]. 'Lhe choroidal arter­
ies are richly interconnected and via short precapillary
arterioles quickly empty large quantities of blood into the
sinusoidal network of Lhe choriocapil laris, probably under
considerable pressure. ]h is blood is drained from the cho­
riocapi] Ian1bed by venous channels thal converge on the
vortex veins. 'Ihe concent rati oil of short ciliary arteries and
Lheir branches in the macular region probably accounts
for greater hemodynamic stress on the choriocapillary bed
posteriorly, t hus any disease process affecting the chorio-
capillary bed and the normal adhesion of the RPE to the
inner collagenous portion of bruch's membrane is likely
to result in exudative detachment of the RPf! and retina
in the macular region, [f the pathologic alterations also
involve disruption in the continuity of the collagenous
or elastic portion of Bruch's membrane, bleeding may
occur either directly from the choriocapiharis as in trau­
matic rupture- or much more frequently from rupture of
new capillaries thal haw grown from the choroid through
3.0 f Diagram of stages of hemorrhagic disciform
detachment caused by type ] sub-retinal pigmen!
epithelium (RPE) choroidal neovascularization.
R, retina; ccr chorioca pi Haris 'See Figure 2.09 for
slages of serous disciform detachmen( associated
with type ] sub-RPE choroidal neovascularization^)
ltruch's metnbracie into the sub-RPE. space (type E choroi­
dal neovascularization) or inLo the subretinal space (type
]] choroidal neovascularization] [see chapter 1). Ihe
stimulus for this process, referred to as choroidal neovas­
cularization. is unknown and probably is multifaclorial.
Liberation of angiogenesis factors from the RPE or retina
in response lo chronic ischemiar chronic nutritional depri­
vation, and other pathologic alterations caused by a vari-
eLy of diseases have been shown as vasoendothelial growth
factors (VLG]:J. 'type IE subretinal choroidal neovascular­
ization can be produced experimentally.1 '
M E C H A N IS M S O F S E R O U S A N D
H E M O R R H A G IC D IS C IF O R M
D ETA C H M EN T O F THE M A C U L A
Diseases of the choroid cause exudation and localized (dis­
ciform) macular detachment primarily by three mecha­
nisms: (1) increased permeability of the choriocapiUaris
associated with loss of adherence of the RPL to Bruch's
membrane; {2} choroidal neovascularization; and [3J
increased permeability of the choriocapil laris and devital­
ization of the RPE. Ihe reader is referred to Chapter 2 for a
discussion of Lhe various pathophysiologic, histopathologic,
and fluorescein angiographic changes that are associaLed
wilh these types of detachments and the histopathologic
and fluorescein angiographic features that accompany them.
'L'he histopathologic stages of focalized choroidal exu­
dative RPE and retinal detachment unassociated with cho­
roidal net)vascularization and those caused by choroidal
neovascularization have been illustrated diagram mali-
cally in Chapter 2 [see L-'igures 2.04 and 2.09). I he various
hemorrhagic and reparative stages are illustrated diagram­
matically in l-'igure 3.01. Each of these stages of changes
occurring anterior Lo Bruch's membrane, irrespective of Lhe
underlying choroidal disease, presents a characteristic oph­
thalmoscopic, hiomienoscopie, and fluorescein angiographic
appearance Lhal will be illustrated in subsequent discus­
sions of the underlying diseases. Ihe palienL with focal dis­
ease affecting Lhe choroid often remains asymptomatic until
he or she develops detachment of the overlying RPE; and
retina (as in a non-or minimally leaking occult neovascular
membrane), ibis detachment may obscure the underlying
choroidal lesion. \he clinician's initial problem, therefore,
is to recognize the presence of disciform detach mettl and to
identify its stage. By careful examination of the surrounding
fundus in the same eye. and particularly the macular region
of lhe opposite eye, and by consideration of the medical
hislory and other physical findings the clinician can often
determine Lhe nature of the underlying choroidal disease.
e p ith E :iu m ar>d ne1ir-a
S P E C IF IC D IS E A S E S C A U S IN G
D IS C IF O R M M A C U L A R
D ETACH M EN T
Idiopathic Central Serous
Chorioretinopathy
Clinical Features
Idiopathic central serous chorioretinopathy (LCiC}, previ­
ously referred lo as central serous retinopathy, idiopathic
flat detach menl of the macula. and central angiospaslic
retinopathy, is. a specific disease- lhal typically affects young
and middle-aged m iles with type A persona lilies between
20 and 45 years of age.1''" 0 Unusual emotional stress fre­
quently .accompanics lhe onset of visual symptoms. 'E'here
may be a history of headaches, which occasionally are of
the migraine type. Males are affected more commonly
Lhan females by approximately 10 to 1. liefore the onsel
of symptom s., most patients develop one or more small
areas of serous detach menl of the ttPE in the in acuta or
paramacular area (Figure 3.02A-Q .1' l3rlJ 'Ihis may be
followed by serous detachment of the overEying and sur­
rounding retina (I'tgure 3.02 D-F). If the detachment
does not extend into the central шасиЗаг area, the patienl
is usually asymptomatic (figure 3.02A-C]). lhe retinal
detachment may resolve spontaneously (Figure 3.02G).
When the detachment spreads inlo the central macular
arear lhe patienl typically develops metamoiphopsta. a
positive scotoma, and micropsia [E'igures 3.02E), 3,03, and
3.04). An occasional palienl wili describe ntacropsia with
the affected eye. Macropsia is the result of crowding of
the photoreceptors in a unit area and micropsia is due lo
decrease in their number in a unil area. A relatively posi­
tive central scoloma and metamorphopsia can usually be
demonstrated on Amsler grid testing, '['he micropsia may
he unappreciated by the patient until demonstrated by
confrontational comparison of image size of the examin­
er's head. Some describe the micropsia as "objects being
farther away with lhe affected eye as compared with the
normaE eye." lhe visual acuity is often only moderately
decreased and may be improved to near normal with the
addition of a smalt hyperopic correction. 'E'here is a delay
in retinal recovery time after exposure to bright light, loss
of color saturation, and loss of contrast sensitivity, l'he
patient's past medical history, family history, and general
physical findings are usual Ey un re markable. lhe author has
seen two instances of JC3C occurring in siblings.
3.02 Idiopa Ih ic centra Ese ro us с ho rio re Linopa thy.
Л-(..: Localized serous detach mefl( erf the relinal payment
epithelium i.RPE: arrowy A) w ilh a small halo of surround­
ing reJinal detachment in a 34-year-old man with a serous
deLat hfrtenl c f the гласи Li in lhe righl eye. H e was asymplom-
aJic in the leJl eye. Mute that Lhe detach men! does not extend
into the fowea. I-Eis visual acufty was 2 ( V I 5. Afiglogjgphy
outlines lhe a r™ (it hi RE delachmenl (E3>. Six monlhs laler
spontaneous reattachrnenL oP" the Rl-3t occurred fC).
D - l А 3 7 -year-old wom an with blurred vision seconda*y
Lo serous delachmenl or Lhe relina. Nole slLghl cloudiness
□f Lhe s u b jo in s I esudale and the moderaleily large under­
lying RPE delachmenl (arrows, Dj. The K.RE is mottled where
it is detached. There is a small KPE detachment outside Lhe
area of m acular detachment superiorly. Stereoscopic angio­
grams ■;£ ап-d Fl showed dye pooled in lhe region of Lhe
HF’l: delachm ent benealh Ihe retinal delachmenl as well as
benealh the smaller liF'E detachment superiorly (arrow, F).
Two months later I here was spontaneous resolution oj Lhe
relinal deLachmonl and slij^hl enlargement of lhe- RRE detach­
ment (<j )j In lh e Tight eye she had developed three paracen­
tral R l’t delachmenl-s (H and ]j. She was asymptomatic in
both eves.
)—L: This 40-yea r4 )ld man had serous retina! delnchmenL^
multiple small aibre(ina] precjpilales, and a small serous
deLachmenl of the RPE iarrows, I and Kl. Angiography dem­
onstrated lhe site oE a serous deLachmenl tjf lhe RRb terrow.
Ю. L is a diajjr^ni of |. The black dots represent fluorescein
LhaL stains lhe exudaLe benealh Ihe delached RH : bill (b e S
ncH enter the subrelinal space. 5RFr subrelinal precipi I ales.
Ophthalmoscopically and biomicroscopically, a well-
defined round or oval area of shallow elevation of Lhe retina
in the macular region is the typical finding [Figures 3.02­
3.04). 'E his area usually presents a slightly darker color than
lhe surrounding normal retina, 'l'he foveal reflex is attenu­
ated or absent.'Elie detachment may be relatively inconspic­
uous ophthalmoscopically but is usually readily apparent
on slil-Jamp examination of the macula with a fundus lens,
lhe stereopsis obtained by using a wide light beam directed
from a few degrees off the visual axis is generally adequate
lo appreciate separation of the retina from the underlying
Ш1]:. Observation of the increased distance separating a
retinal vessel from ils shadow cast on the underlying RF£ is
another helpful clue to the presence of serous delachmenl
of the relina. Separation of the narrow light-beam reflex tra­
versing the retina from that striking the ftPE, when demon­
strable- is further evidence of a serous delachmenl. En some
instances, particularly in the presence of a shallow detach­
ment, this separation may be impossible to demonstrate.
Rtlina

ERF

л i-'-vWa-

Sclera
 The detached retina is usually transparent and of nor­
mal thickness, '['he sub ret Inal serous fluid is usually clear.
Ibere may be a small round yellow spot- probably caused
by increased visibility of lhe retinal xanthophyll. in the
center of the fovea. This may be mistaken for a sma]! RPE
detachment. En some cases lhe posterior surface of the
retina may be partly covered with multiple yellowish dol-
Eifce precipllales [E'igure 3.02J). In approximately ЮЯ-b of
eyes the sub retinal space may be partly filled wilh a gray-
white serofibrinous exudate that may be misinterpreted
as a focal area of acuLe retinitis, an Ischemic infarction of
the relina. or a sub retinal neovascular membrane (Jigure
3.03])Л' Serofibrinous exudate es oflen associated with a
larger area of retinal detachment as xvell as more promi­
nent fluorescein leakage Into the subrelinal Hu Id [figure
3.03A and I.). 'Ihe serous detachment of the RPE under­
lying the retimil detachment is variable in size and in
some patients is often impossible lo detect Without (he
aid of fluorescein angiography [E-'igure 3.03A), 'typically,
il appears as a round or ova!., yellowish or yellowish-gray
lesion that is Less than one-fourlh disc diameler in size
(E'igure 3.02J). '['he surface of the R r i delachmenl may be
finely molt led (figure 3.02 A D,. C3. and llj.
A small КРЁ detachment is easiest to delect in retro-
iliu mi nation adjacent to the slit beam of light focused
on the RPE. It is usually located beneath the superior hnilf
of the area of retinal detachment. [I occurs infrequently
in the center of the fovea. !n some cases the FiPii detach­
ment may appear to Lie beyond the superior margin of
the retinal detachment. Ilecause of gravity the sub retinal
fluid tends Lo pool inferior to the area of serous detach­
ment of the RE^L. [Positioning lhe patient may be required
to demonstrate continuity of the areas of retinal and RPE
detachment. Focal detachments of the RPE are difficult to
visualise biomicroscopically when they are small in size.,
shallow in depth, or obscured by turbid sub retinal exu­
date. E'l uorescein angiography may he necessary Lo detect
the sile of RPE detachment.
Multiple ЯТЕ: detachments may occur (Figures 3.02[J
and H. and 3.03). Occasionally one or several detach­
ments of the Rl]li may lie outside the primary area of
retinal detachment (Figure 3.02L>). In lieu of a discrete
3.03 Id iopa Ih iс centra [ se rt>us cho rio re tin opa thy.
A —F: ’Ajunjj wom an wiLh serous retinal ctetachm^iL Note
small relinal pigment epilhelium iKF-’t leak iitfenonasally H^nd
w indow dufed temporally in E3. Angiograms E3—tJ, including
slerwjangiorgrams D, show dye flre-nming superiody inlo the
suhretinal space. Nole syld^fice o f um;ul fb tal leak ■iiLrrtyw.
D ' in lhe area of lhe w in d o w d e le d temporally. L is n dia­
gram illustrating riii:u--ion of the dyu |iu ip liii£ j from lhe cho­
roid into lhe sub-HFE space and then into the subretinal
space ihrough a break farrow i in Lhe КИЕ:. F is л represen­
ts live optical coherence tomography showing a small RPE
detachmeril w ilhin thfe area of serous retina] delachrnaif,
G-l: Serous retinal detachm ent overlying moderately Urge
RPb detachm en; w n fluofeh( eir> streaming Ihrough small
defect iarrow y H and I in dom e of K I3Ei delachmenl inlo
subretinal space.
3—L: ^iefouh delachm enl of reLina w ilh whitish sufjrelinal
fibrin surrounding small K l3t detachment rn a 40-yoar-old
man. Note heavy fluorescein slaining in area of fibrinous
eKudale а-н w l :II as lhe serous exudate elsewhere in the suh-
relinal space.
RPE detachment there may be an irregular, roundr or
flask-shaped area of mottled depigmentalion of the
RPE beneath the retinal detachment (Figure 3.0FH-].
3 . 0 and 3.07J Ihis occurs often in patients subject lo
recurrent serous elevation of the RP£ and surrounding
retina in the paracentral area before they become symp­
tomatic from spread of retinal detachment into Lhe central
macular area.
Although RPE: detachments are typically small in
patients with I C SC in some patients they may encompass
a disc diameter or larger. When larger the hlisterlike RPE
detachment may be surrounded by a reddish or salmon-
pink halo caused by a marginal serous separation of the
retina (3:igures 3.02A, G, and H, and 3.04А).|Л|: ^
]jtr^e RE]L detachments are typically circumscribed, oval
or round, dome-shaped, and orange or yellow-gray; they
present a solid rather than a translucenL appearance, it is
these features lhal occasionally cause a misdiagnosis of
a choroidal hemangioma, hypopigmenled melanoma,
or melastalic carcinoma of the choroid (Figure 3.04AJ.
The junction of the detached and all ached RPE: typically
produces a discrete and circumscribed halo surrounding
the base of the Lesion, in contrast Lo the less discrete lighl
reflex halo surrounding an. area of serous detachment of
the retina, ihe choroidal pattern thal is often visible pos­
terior to the serous detachment of the retina is usually not
visible behind Lhe serous detachment of the RPE, except
in the rare case in which there is extensive thinning and
depigmenlation of the detached k P t. L-'ine mottling of the
pigment and dumping of pigment on the surface of the
detached RPF are common [Figures 3.02 and 3.04). ihis
pigment clumping may produce a cruciate [Inn cross bun)
or triradiate pigment figure (ligurc 3.<MA and JJ1. !he vitre­
ous in patients wilh ]CSC contains no inflammalory cells.
Fluorescein Angiography
Angiography in patients wilh iCSC shows a variety of pal-
Lerns. In lhe presence of serous detachment of the retina,
fluorescein angiography identifies the area where the RPli
is detached and where serous exudate derived from the
choriocapi Haris is gaining entrance inlo the subretinal
space (see Chapter In those cases with a discrete
blislerlike detachment of the REnEi.. fluorescein rapidly dif­
fuses out of the choriocapi I laris across Hruch's membrane
atid stains the exudate beneath the RN-. creating a dis­
crete. often round spot of hyperfluorescence, correspond­
ing to the size of the RPE detachment [Figures; 3.02-3.04).
In cases of a shallow detachment of the RFE, the spot of
hyperfluorescence enlarges concentrically during the
course of angiography. In some palients the dye is con­
fined Lo Lhe &Lib-R[: li space [Figure 3.02h, E E, and |).
In others the dye may diffuse slowly through the detached
ЙРЕ to produce a faint fluorescent hai:e in the subretinal
exudate surrounding the ftP E detachmenL. In less than
10% of cases the dye passes through a small hole in the
RPK, often at the margin of, and occasionally within,
the dome of the detached R T F , and streams upward in a
smokestack configuration inlo the subretinal exudate lo
form an umhrelia pattern of fluorescein staining (figure
3.03A-E). I his upward movement of Lhe dye is probably
caused both by convection currents and by the relatively
3.04 Id iopa Ih iс centra I se rc>us cho rio re tin opa thy.
A -С: This 4fl-vmir-[)]el man had a large $ertH_i£ detachniLvil
ot The te lim l pigment e p ilhelium (RIJ Lj. Su-ven yeafjs previ­
ously he had serous m acular detachirafpt in his lefl eyEf IhaL
resolved г а й г Lanetrtisly Sijithifli 2 months. Visual acuily ir>
Lhe rifjht eye was 2СУ5 0. NoLe the sharp rfiargpn ot" Ihe? scrou*
detachment of Ihe К PE (A). There was no scjdUs detachment
o f Ihe surrounding retire. Note also (he pigjnenL figure on
Lhe surface ot lhe delached R P t. Angiography showfid diffuse
leakage of dye across B ru ch s membrane Enlo [he sulj-KPt
нрасе (IS'i. Nole Lhe pignienL figure Outlined ал lhe back­
ground of fluorescein. The palitfnl was observed at yearly
intervals wiLhoul change Ln his visual acuiLy or Lhe apficar-
ance of" Ihe fundus. W h e n he returned 9 yenrc alter lhu pho­
tograph :n A, lhe serous deLachrirujnl of Lhe K]JL had лImust
disappeared ILI and his visual acuiLy was £|У5£}.
D-l: Idiopathic central serous chorlorelinupathy in a
!34-year-old man W ilh a pereislunl serous Не1псЬтел1 of Lhe
macula for longer ihan A mortth.i .[] . А К т о ъ с ч ю и ч phase
revealed preserice of eilher art RPE delachm enl or defecl
in Ihe KL3t, \vhic;h is exlnernely minute (arrow, hi. The dye
ic-.-:-a-:- ii'in ll.c--i.hi4 lin.il v-p.n e .vv:l w.is t .irr:('d M.ifj i ' r i г!у
if . lh e dyt! pooled superiorly in the Huhretinal fluid in lhe
domu of the detachment (ti). O n e day afLer treatment the sin­
gle application of low-intensilv xenon phokKoa^ulaLioji whs
visible (low er arrow, Hj. The two small round spots are lijjht
reflex artifacts. U pper arrow indicates test spot. The retina
was flat 31i weeks afLer photocoagulation flj. Visual aL'uity
was 20/15. The Lest spot was no fonder visihie.
1-L: Subrelinal fiEirin suTrounding КГБ delachment (arrow y
l-L.l i:i Iw o pregnant W om en w h o developed id iopa Ihi с cen ­
tral serous chorioretinopathy during the seventh monlh of
pregnancy, lh e [i^tgehment disappeared earlv р<к1ряг 1и т in
both patients.
|A-t frum Cj;i5x c[ al J-*; J and k. fium Олыь.--1.. 0 1991.. Amentan Medi-cal
Aifstx :;ilMjn. АЛ мцЫк n.'st'rwcL.'i
higher specific gravity of the dependent subretinal exu­
date.” Eventually the entire subretinal exudate may stain
and appear hyperfluorescent, except in the foveal area,
where the luteal retinal pigment obstructs the pathway of
the exciting blue as well as the emitted fluorescent light.
Pelinal detachments associated with "■smokestack''' leaks
are generally larger in area than those with focal leaks.-’ '
bpi'cific Diseases Сдып'лд D fxifprm M ncuixr D flachnn'nt i I
72 1 Н \ ■i 3 Diseases C ausing Ex u d a tive and H em orrh agic Detachm ent
In palienls with irregular 1ЩЕ detachments and atrophy.
Lhe pallern of hyperlluorescence is correspondingly irreg­
ular pjrLLeu]лrly during the early phases of angiography
(Figure 3.05 И acid C). Patients with gray-white sub retinal
serofibrinous exudate usually shdW ilreaming of dye into
the tub retinal space near lhe exudate [E'igures 3.Q3J-L
3.0GA-Cr and Э.ОЙА-О),32,34'35 After resolution of lhe
macular detach menl. the angiographic findings may return
Lo normal. However, angiographic evidence of lhe small
RPE detachment may persist in some patients. Irregular
Loss of pigment from the ftP£ after prolonged retinal
detachment will be evident angiographically as mottled
areas of hyperfluorescence that tend Lo fade during the
course of angiography Angiography is helpful in detecting
Lhe large zones of exlramacuiar depigmentation of Lhe RFE
caused by chronic retinal detachment in patients; wilh a
more severe chronic form of this disease (Figures 3.05 and
3.06}.u-l!' in the majoriLy of cases the leaking sile is found
within one disc diameter of lhe cenler of lhe fo v e a .‘ The
foveolar area, however, is infrequently affected.'''
Approximately 30% occur in the superior nasal quad­
rant and 15% in the papillomacuEar bundle aiea.J ‘
Angiography, however, should always include photographs
of lhe paramacular areas as well as lhe macular regions
of both eyes. It is particularly important to photograph
those areas superior lo the macula and optic disc on the
side of lhe macular detachment to delecl eccentric areas
of leakage, which, because of gravity, may iie superior lo
the area of delachmenl. Scanning the fundus during the
Eater phases of angiography may be necessaTy lo delect
exlramacular areas of fluorescein leakage. Failure lo find
evidence of a leak angiographically in a patienl with a
serous detach men! of lhe macula should suggest the fol­
lowing possibilities: (1) a leak has occurred outside the
macular area, usually superiorly; (2) lhe leaking area has
Э.Оа Multifocal and recurrent idiopathic ten Ira I
serous chorioretinopathy^
Л -N : This 42-year-old jSsjoman w ilh lupus nephropathy who
bad undergoпЁ л renal {JrajT^plarct 7 years previously noted
a change in vision in her left eye in 2 005. The rEght eye was
un involved and saw 2 0 /2 0 w hile vision in lhe left eye bud
dropped (a 20/?0. A single packet of subrelinal fibrosis ( SR F>
associated with orange flecks was seen extending tempo­
rally from (.iie disc -.A'. An angiogram revealed leopard-spot
chang^f with transmission hyperfluorescence ot I ho? area nol
blocked by the orange piymenl that remained dad;. There
were fou: hoL spols af hyp&fltiOrestence, She was fibserved
and the serous delachmenl resolved sponl.a леон sly in 2
nionLhs. 'She relumed 3 Vj years laler w ilb symptoms in her
rifjjil е Уе fnam a pocket ol" 5iRF temporal to the fovea. An
angiogra rn revealed pate by leopaid-spot change in bolb
eyes, five bot spots on the right, and a single one on the left.
She underwent focal laser lo lhe hoi spots in Ibe fight s?ye
wiLh resolution o f fluid in 2 months lK-N'i. Autofluorescence
images show increased auloiluorescence corresponding lo
the ornnjje pigment and decreased aulofluorescence corre­
sponding 1o lhe rdinal pigment epilhelium loss It and h.
healed and the delachmenl will disappear within the next
few days or weeks; [3] presence of a peripheral retinal hole
or choroidal tumor (usually superiorly located); (4) a con­
genita! pit of Lhe optic nerve head is present; and. (5] idio­
pathic uveal effusion syndrome flLILS) is presenl.
Studies of palienls with ECSC wilh indocyanine green
have shown congesled and dilaled choroidal vein and cap-
ill aries, choroidal staining and leakage inlo the extracellu­
lar space lhal appears as areas of hypcrfluorescence in the
middle and late phases. This renders evidence of a broader
area of choroidal involvement than that demonstrated by
fluorescein angiography, hence the better name. IC SC.1
 Aulofluorescence imaging depicts a variety of findings
in ]C5C. 'l'he orange spots seen in acute I CSC lhal may
be sites of fibrin; lhe subretinal orange deposits Within
ап area oJ" serous detachment which could he fibrin alone
or mixed with photoreceptor elements; and serofibrinous
plaques that resemble relinitis all show increased auto­
fluorescence (Hgure 3.0JD (p^row) and I } . 1' Jn eyes
wilh chronic and recurrent ICSC/sleroid-related/organ
transplant retinopathy, areas of RPJ£ atrophy are seen as
wide gutters of hypoaulofluorescence.. the edges of which
show increased auto fluorescence [E'igures 3.06 L and Hc
and 3.07С and L>). Aulofluorescence imaging With ils
mixed areas of increased and decreased auto Fluorescence is
exiremely typical and is a useful non invasive technique in
eyes suspected of chronic recurrent 1CSC.
Choroidal congestion and thickening can be confirmed
by ultrasound К scan, and more recently with enhanced
depth imaging on optical coherence tomography (QCT)
using Spectral is.'14 'l'he patient's eye is brought closer lo
the OCT machine than during conventional retinal scan­
ning- and this enables the choroid to be visualized. Lyes
with ICSC have been found lo have a ihicker choroid as
compared Lo normal eyes. JEigh-resotuLion imaging of the
cones in the posterior pole with adaptive optics scanning
laser ophthalmoscope may prove lo be useful in monitor­
ing progression in eyes wilh chronic/sleroid-associated
IC SC ^ T h e technology is still evolving and the instrument
cost precludes its use routinely.
3.06 Ch ron ic recurre nI idio pa th it ce it ral sero us
chorioretinopathy associated with large dependent
zones of depigmentalion of the retinal pigment
epithelium (RPE) and migration of pigment into the
overlying retina,
A-*. : A
47-year-old n n n com plained ot" bilateral loss of
paracentral and superior fields -of vision and difficulty driv­
ing Hi nif^iL o f 4 years' duralion. Note iforves of" alnophy of
FiF-’t l.mows,. А лиг! Bi. Angiography showed m ultiple zones
oi" KKE atrophy and multiple leakage sites (arrows, О .
fclecLrorelinography was w ilh in normal limits.
D-l: Com posite -oi lundi o i a ti4-year-old man with a long
history o f bilateral recurrent Episodes of loss of vision caused
by serous detachment o f Lhe reUna. H is vision could lie cor­
rected to on lhe ri^hl and 20;!> 0 on lhe left. Soto
prominent zones of R PE changes extending Lo Ihe ora serrata
inferiorly. The areas o f RFh loan лррелг hypoautofiuofesccnl
IE and Hi. increased ,iulofluoreHcerrce is seen turroLmding
Lhese iiri'ai, su^PbLin^ the neighboring K3J t cells ir e invest­
ing bro-kon down pholonucepLor and oLhor cellular maleriaf-i
The Hgfit eye w j s drv (FI; the lofL Khowed Khallt>w s u-brel i rui I
fluid 'Г, for w lik li he received low-lluence pholodynamic
thenapy. H e did not recall sLeroid intake bill may have
received injeclions. Lo hiн wrist join!.
1Л -1 f r u m < _l;n s.''"
Atypical Presentations
Chronic IC S C
So pie patients, particularly La Lins and Orientals. dew! op
multiple sites of prolonged and recurrent serous reti­
naE detach mem in one or both eyes {figLBres 3.06 and
3.07}. Ihese initially may be confined to the juxlapapLl-
Eaiy, peripheral macular, or extramacular areas, and these
palients may lit’ asymptomatic for many years before
they develop a focalized detachment of the macula. By
this time there may be multiple, often teardrop or long­
necked. flask-shaped areas of atrophy of the ЁРЁ extend­
ing interiorly from the paracentral and particularly the
peripapillary areas lo the equator, or ora serrata (figures
3.06 and 3.07).::',::<,,,tL'1 Occasionally large dependent
areas of highly elevated chronic serous detachment may be
mistaken for retinoschisis [figure З.ОвП- L j.|:' Recurrent
detachment in these areas causes atrophy of both the KJ4:
and retinal receptor elements. A bone corpuscular pat­
tern of migration of pigment Into the atrophic retina may
occur in these zones and may be misinterpreted as evi­
dence of retinitis pigmentosa [figure 3.06G and 3.07A
and Ji These palients may have extensive Loss of the
superior visual fields, and some anay complain of diffi­
culty driving at night. Angiography often reveals multiple
focal areas of staining that usually are most prominent
near the superior aspect of the multiple zones of hyper­
fluorescence thal correspond to the areas of R T t atro­
phy. This atrophy and staining are frequently prominent
in the jufcLapapillary region of both eyes (figure 3.06C).
Autofluorescence imaging is particularly usefuE in detect­
ing the complete extent of the RPE involvemenL and is a
useful non invasive method to monitor the progression
3.07 С hron ic recurre nL idio pa th ic ce ntral sero us
chorioretinopathy resulting in pseudorehnitis
pigmentosa,
A - D : This presently i>.l-year-olrl man was fol lowed lor more
than 17 years with recufrenl and chronic centra] serous cho­
rioretinopathy. A few episodes o f acute leak were treated
w ilh gentle focal Inter in both eyes. The righl eye lost cenlral
vision insidiously about b years into the disease. Dark adap­
tation becam e difficult in the pasI Ъ years. Note Lhe focal
areas o f deep chorioretinal alropby and jieneralizttd loss of
relinal pij^m c*nI epi I helium KIPLl and superficial chorojd in
Ihe inferior fundus. Hone s-pjcule pinment migration is seen
in iiolh eyes 'A and Jl'i. Ih e vision in -his lighl eve is 2tV4Q0
and in Ihe left eye 20/20-. Autofluorescence imaging shows
gutters of R PE loss from fluid gravitating infertofly arrows.
(C and L>j.
in patients (figures 3.0&L and El and 3.07C and D). 'lhe
involved RJ3f is bypoautofluorescent with the area just
outside it being byperautofluorescent, suggesting increased
metabolic activity Ln the adjacent intact R P l i (figure 3.06f
and Kj. 'Ihese patients are particularly prone to recurrent
macular detachmenl and may permanently lose significant
visual acuity and paracentral field. With chronic detach­
ment lipid exudates and cystoid macular edema may occur
in the absence of angiographic evidence of subretinal neo­
vascularization. Chronic serous detachment of the inferior
retina may cause, in addition lo large areas of retinal and
RFE atrophy, loss of the retinal capillaries, retinal neo­
vascularization. vitreous hemorrhage, and electroretino-
graphic changes (figure 3.03J.'":■'lfi■|,' Long-term follow-up
studies of patients with Lypical 1CSO have demonstrated
that these patients with chronic recurrent detachment and
severe visual loss are part of the spectrum of l0Ei0.4t'"" ''
78 J Pi'.cM'ii's Ciiummp Lau d a tive am i IK m o rrh a ^ k Detachm ent
A cute Bullous Retinal Detachm ent
Multiple areas of serous deLachment of the retina maf
occasionally develop rapidly in the same or both eyes of
patients with I CISC.|: ■’ Lbese may occur in the midperipb-
eiy of lhe fund ил as well as in the poster ior pole. In a few
patients these detachmenls may become confluent and
result in a large buildup retinal detachmenl involving the
Lower half or more of the fundus (figures 3.0BA-C, and
3.10}.^^® ^55 ihis acute severe form of 1CSC es particu­
larly likely let occur in otherwise healthy patients ivho, as
Lhe result of a misdiagnosis, receive systemic corticoste­
roids.1' Multiple serous detachments of the RPL, often
Vi-1 disc diameter or larger in size. are typically present.
Jhey are frequently partly obscured by cloudy and at limes
gray-white fibrinous subretinal exudate. A similar pic­
ture often develo p s in the second eye within several days
or weeks, lhese patients may be misdiagnosed as haviEtg
a rhegmatogenous detachment, multifocal chorioreLini-
tis. metastatic carcinoma, lEarada's disease., or uveal effu­
sion. The angiographic demonstration of multiple serous
detachments of the ЙРЁ [Figures З.Ш В and Cj underlying
shifting subretinal fluid permits an accurate diagnosis.
Fluorescein characteristically streams through a hole in the
pigmenl epilhelium at lhe edge of the large KPb detach­
ments inlo the subretinal exudate (figures 3.08К and С,
and З.Ш С and D J,35 15 ,h Occasionally, large l*E*b rips may
occur al the edge of lar^e КРЁ detachjneEtls (Figure 3 ШГ1,
I and K ).^ ir
3.(tS Severe idiopathic ceniral serous
chorioretinopathy ■;I CSC) with bullous retinal
detachment in otherwise healthy patients receiving
systemic corticosteroid therapy.
A - C : 1his- 45-year-old man in il iл 11v presented w ilh л serous
detachlfienl of lhe ftiacLlja in lEio rif^Kt еу)Ё. I: was attributed
La choroidFlis and Ihe palient received oral prednisone. This
was lolluwed by tjilaleral bullous retftial de 1a(.hment asso­
ciated w ilh multiple large serous retinal pigment epithe­
lium FiF’t: detachments., some of w hich went' suirountled
by a cloud Ы white ГгЕэппоиь subretmal exudallon (arrcjws,
Al. Fluorescein tlve si reamed through small breaks i arrows,
E3) in the dome of lbe bTL delHchrnenls Into lhe subrelinal
space. Н.еь<1lu I ron ai" tiic suh filin al exudale o cc lirfed after
pholocoHjiulation of KPb detachments And slopping Lhe cor-
Ikosleroid^. rhe paJieiil had no furlhur episodes o f m acular
datachlfienl Until 63 years (if aye, w hen he? developed tubrol-
inal net jvascu-la гi га Li t] n al Lhe site of treated KTE detachment
superior lo Lhe rFp;bL tovea.
D-L: This 1/-year-old m.in developed bfflffleral serous
delachmenl of the m a c u Ji (D ) in In t Э90, in ,iddi-
tfiari 1o a ch-Tonic com phiinl o f subnormal vision, he devel­
oped floaters. L-ii Iл1егс11 peripheral! bul(aLla retinal elevation
inferccrEy and several lufts of relinal neovascularization were
noled (arrow, £ . Thn^o changes were aLlribuled to X-l inked
juvenile relincjschisis. In 199f1> in spile o f flieriiescEirt an^io-
urapfiic findings lhal suj’vesled chronic recurrent 1C5C ih
ai>d Cl , ihD diagnosis Wag relinal vasniliLis and tTea!menl
with systemic corticusleroids resulted in severe bilateral
bullous relina] detach monl, incorrectly aLlriliuled lo UveaJ
effusion syndrome. In; '1993, hi I a Lera I scleral windows., vor­
tex vein decompression, and larger doses ol corllcosteroids
resulted in massive subretinal serofibrinous exudation ГН
Lind 1). Arrows indicate foci of relink I neova sculariiaLion.
Fluorescein angiogjapEry revealed mu I Li Iota I areas of R PE
elevation nind decompensalion posteriorly, Eeakage from sev­
eral loci of relinal noovasculari nation i.,irro\vs, 11, and ,i bnjiid
гопе of netiiiH-il fapillHrv nonpeilusion i-nHrriorlv in b o lh e ye s
(K). A ller discontinuance ol Ihe corticosteroids the retinal
delachmenl resolvud prom pi k. leaving subrelinai frbrtius
bands in lhe m acular region of bolh eyes.
ID-L Trcmi Li.ibi .md Ljllk\j5(
 All of the otherwise healthy paticnLs wilh bullous reti­
nal detachment complicating LCSC seen by Gass have
beer middle-aged men. By lhe time he examined ihem
many of Lhem had diagnoses other than 1C5C and were
receiving oral corticosteroids,1],4& ]'hL& same clinical and
angiographic pjclure щйу, however occur occasionally in
women, particularly those receiving,corticosteroids for sys­
temic disease, e.g., disseminated Lupus erythematosus.
Crohn's disease/’1 rheumatoid arthritis/'’ hemodialysis/'"
and renal transplantation (Figures 3.11 and 3.12}." Ln
addition to these disorders Gass has seen this severe form
of LCSC in women with hemolytic anemia, cryoglobulin­
emia, eosinophilic /asciilis, severe atlergic bronchitis alter
commencement of systemic corticosteroid therapy, and in
one woman with multiple peculiar cutaneous and mucous
membrane vascutar malformations infiltrated wilh mast
cells [figure 3.. i J A-F).
Al the 13d2 Kaslern Ophthalmic Pathology Society
meeting Dr. Gilbert de Venecia reported the histopatho­
logic findings in one eye of a 40-year-old Native American
man who soon presented after a kidney transplant with
bilateral bullous retinal detachment and multiple serous
KFh detachments surrounded by white sub retinal exudate
(E'igure 3.12b and H).J " '■'iA''1lie found histopathologic evi­
dence that the whitish exudate beneaLh and surrounding
the R PK detachment was fibrinous Ёп lype (figure 5.E2G
and IE).
tC S C Associated with Chorioretinal Fofds
I CSC may occasionally occur in eyes Wilh choriorelinal
folds in the macular area secondary lo choroidal conges­
tion (E-'igure .3.0L>L and M)>
I C S C in W b T n e jj
JCSC in otherwise normal women is similar lo lhal in
males except that onsel tends lo be al an older age in
women.'0 ECSC in women receiving exogenous corticoste­
roids is more likely lo be associated tvith bilateral involve­
ment and subretinal fibrin.
Central serous chorioretinopathy in lhe elderly.
Acute idiopathic cenlral serous chorioretinopathy
(IC5C) with sildaneiil use,
A-F: This fi4-year-old man presented w ilh a drop in vision
in his right eye lo 2tV30. There Wasi a sm aolh turaut relinal
delachmenl Without any dresetl ^ le n d in g from lhe disf.
eri|^e to lh e fovea A). A n ^ io ^ am showed a mi It! lale hyper-
tlLldrascenl spol l-umporal lo lhe dist edge that was Eiyperau-
LoTluoretcenl (B-D ). The serous detachmenl w as smooth on
uplical coherence lomography iOCT.i without evidence of
drusen or olher RPE: abnormalities itj. Lighl laser to this spot
caused resolution of mosl of Ihe subretirtal fluid \Hi w ithin
4 weeks and return o f vision lo 20/20.
N ew -onset steroid-induced 1CSC with leopard-spot
change in the elderly-
G - M : This 72-year-old male w ilh no pjhftfiCJLis ocular his-
Lory experienced fluclualin^ vision more in his lefl eve ihan
rigjit- H 's glasses prescription had Ю etu corrected twice and
lie underwent calnracl sur^-ery i-п rhe lutl eye. Four weeks
followiiWf calaracL surgery he was noled lo have cystoid
macula г edema on the lefl eye and received a sub-Tenon
injeclion o 1 triam cinalone. H it vision dropped further. W h e n
ела m med а т о л I h Iл I or his vi sion w a s porrec I abl e 1o 2 Q/iO
on the righl and 20/.‘5O on Ihe left. Ln addition lo tEie flast-
shaped serous tfeacftm ent in Ihe lefl eye there were chorio-
nelinal folds (G and Hj. N o peripbera] choroidal delachm enls
were seen. Inner relinaE fEuid wan present in both eyes and
subretinal fluid in the lefl eye on O C T and K). Huorescein
showed only a leopard-spoL Lhanjje corresponding lo Hie
subretinal fluid wilhoul significanl breakdown of Lhe K P t >!L
and M l1. There was mild hyperfIuorescence al lhe disc edge
lhal was attributed Lo peripapillary atrophy. He denied s1e-
noid intake at any time, lie was a well-controlled diabetic
and hy|jeHensive w ilh a blood pressure o f 1 .lil'78 m-mhtg in
lhe office, a nil was in good heallh. His serum liuhl chains
were slightly eleva1ed bul M-protetn spike was absent. O n
lurtEier (]uesLir)nin|^ and tpeaking to his primary phytician^
lie was found lo have received three inLramust ular injedions
□f sleroids xJver lhe previous Id months for rata l congestion
and Lined penile inj eel ions of papaverine. prosLaglandin, and
phenlolam ine Гот impotence for Lhe previous 2 years.
 I CSC may occur in healthy women during the lat­
ter half of otherwise uncomplicaLed pregnancy.JJ 7l-7b
For unknown reasons it is associated with white subreti-
nal exudation surrounding the &РЁ detachment in over
90% of affected pregnant women." ll is important not to
mistake this serofibrinous exudation for evidence of suh-
retinal neovascularization, load retinitis, or focal retinal
infarction, all of which may suggest investigations includ­
ing fluorescein angiography, which are usually unneces­
sary in the differential diagnosis. Jhe detachment resolves
spontaneously soon after delivery and lhe visuid prognosis
is excellent. ICSC may oi may not recur during subsequent
pregnancies.
fCSC in the Elderly
Although most patients with ICSC are young and middle-
aged males, some first develop symptoms in the laler
decades of life (Figure 3. IEC-H ).' 7Щ 'l'he clinical picture
may be identical to lhal occurring in younger patients,
although a larger percentage of the older patients will
manifest fundoscopic evidence of previous episodes of
subclinical eccentric relinal delachmenl. as described pre­
viously. in older palients there is more concern lhal the
focal Leak demonstrated angiographically may represent a
focus of occult choroidal neovascularization. Although an
occasional patient with ICSC! Will eventually develop evi­
dence of AMD, there is no evidence that the two diseases
are more than casually reEated.
ECSC asso dated with siklenati
More older males are presenting wilh ICSC associated with
use of agents for erectile dysfunction such as sildenafil
[E'igure З.ОУА-!7) / '" 1'1 Unlike older patients with drusen
and age-related macular degeneration [AM D), the smooth
elevation of lhe photoreceptors and no areas of R PE
humps caused by drusen (Figure 3.0УН) on О С I' should
prompt the diagnosis of iCSC. Cessation of sildenafil
use caused resolution in most palients and some showed
recurrence oil resuming lhe medication.
ECSC with leopard-spot retinopathy iin elded у
patients on systemic steroids
]h is fundus appearance of yellow deposits in a "reticulated
Eeopard-spot fashion" was brought to attention by lid a
Et al.'1
- in 2002 as a newly recognized finding in 5 older
men between 6Й and 81 years of age receiving systemic
3.1E) Severe idiopathic central serous
chorioretinopathy (IG $Q with bullous retinal
detachment in otherwise healthy patients receiving
systemic corticosteroid therapy.
A -F: This 11 -year-old man developed detachttrenl of the
Ioft p c t l l a a^KociaLed w ill: a Focus of subreHi-nal flbrifi lhal
was- mi s i nLerpreled ms acute relinilis. Тпеа I mont for toxoplas-
musLs, including prednisone, was given. O n e week laler the
Hrapent had bullous sejjhal'ibrinou^ relinal deliichriient in lhe
rinhl eve and juxLapapillary and macutar reLrnal detachment
in lhe left eye (A and H). Large serous detachments cjI the
FiPt surrounded by bubreLinal fibrin wure present I>ilaterally.
The dt'La-Lhmenl resoived com pletely W ithin 2 Weeks alter all
medications w ere slopped. H e remained asymptomatic and
at Fast examination, 11 years later, had 2 0 /2 0 bilaterally.
f=--K: This 5-t-year-oJd man m ainlained near normal visual
acuity in spite of a 31 -year history o f recurrent eprsodes of
ГСУС, unLil lie developed an eprrelinal membrane in Lhe
righl eye. O n e day before scheduled vitrectomy he devel­
oped ICSC in Lhe fellow eve. Hu was slarLed on a course of
prednisone 100 mg/day preopera Lively. WiLhin several days
or surgery he developed bilateral bullous retinal delachmenl.
PostoperaLively lhe oral prednisone was tupplem enled by
reUobulbar Injection of corticosleroida. Six weeks postop-
eraLively his visual acuity was 20/400, njjhl eyor and couitL-
in^ fingers at 2 leel (60 tm l, left eye. There was Lola I bullous
ruliral delachm enl associated w ilh mu I Li pie large relinal
pigment epiLheliu-m Kl-1h I delachnnents b i 1д1е?гл111.- associ:-
aled with Iibriп-olis exudation and subrelinal fibrous Eiand
formation IC and Hj. In the left eye Ihere was a 300° Lear
ia nov/s I along Lhe ed^e of a lar^e H.PL delachm enl involving
Lhe superior тасиЭаг region l-ij. Angiography confirm ed Lhe
presence of mu I Li file bil^Ei detach merits in I h c*- right eye (I) Hind
Lhe RF’t tear in Ihe lell eye ijj. iMHe lhe irregular retracted
Eid^e I a n o w i dtf the Lorn KF’l: and lhe fluorescein slaining
wiLhin the urea of missing KiJ L. ti^hleen monlhs laler, after
corticosteroids w ere slopped, and afLer multiple opeiaLive
procedures, a fractional retinal delachmenl was sLill prc*senl
in the righl eye, but the relina in lhe let! eye was Teallached
iK) and lhe visual acuity had relumed to 20/30.
Ю - К Iг о т (J.jm ,: 11:1 L : L l J e . ' ' I
corticosteroids. However this same pattern was previously
described by Gass et al. in 1992 in patients following
renal, heart, and henrl-lung transplant who were receiv­
ing systemic steroids (see E-igure 3.b0A-E.J. Corticosteroids
seem to be the common factor IiLiking these two groups of
patienls (Figure 3.09£ and M l
84 I L HA PTE R 3 Diseases C ausing Ex u d a tive and H em orrh agic Deta chment
tC S C Simulating Pattern Dystrophy
Patients presenting wilh the typical findings of ICSC
may over j period of years develop multiple focal yellow
Eesions with pig men Led centers in tine or both eyes, slflffi-
Ealing lhal seen in patients wilh pattern dyslrophy. ibese
lesions may also simulate Klschnig spots caused by fibri­
noid necrosis associated wilh severe hypertensionr col­
lagen vascular disease, and disseminated intravascular
coagulopathy (DEC).
O th er Associations with IC S C
lhe author Eias seen ICSC occurring in 2 women in asso­
ciation with retinitis pigmentosa (see I'igure 5.41 Л-С)"-
and with episcleritis.0''-'1’
Prognosis
lhe prognosis for the majority of" patients with ICSC for
spontaneous resolution of macular detachment and return
of visual acuity is excellent."1'c'" 7 )Q Improvement can
continue for up to 6 months after reatLacbmenl of the ret­
ina. However, when tested carefully, many patients recov­
ering 20/20 acuity will still have a mild permanent defect.,
such as a decrease in color sensitivity. Loss of contrast sen­
sitivity. relative scotoma, micropsia, metamorphopsia, or
nyctalopia.'^’-'4''-'-''' Approximately 5 % wilt fail lo recover
20/30 or better acuity. With prolonged and recurrent epi­
sodes of detachment the patient may develop permanent
visual loss lo levels of 20/200 or less. Iliis is more likely Lo
occur in patients with the mu Ilice ntrie chronic form of the
disease.
The prognosis Fof reattachment of large serous detach­
ments of the RIM! is not as good as that for small detach­
ments. Patients with large serous detachments of the
PPL, however, usual Ey maintain relatively good vision for
months or years (l igure 3.04A-C).' ' ' ' "4 Jhere is great
variability in the bio microscopic appearance of the macula
after resolution of retinal delachmenl. In some patients
the fundus may regain a normal appearance. Most, how­
ever, will demonstrate some evidence of irregular depig-
mentalion of the RPEr usually most noticeable in the area
3 .1E Serofibrinous retinal pigment epithelium JRPE)
and retinal detachment occurring in patients receiving
corticosteroid treat in ent for systemic disease,
Л-C: Bilateral multflOcsl KPE detachments surrounded by
fibrinous Hubretinal exudate in a yuvm ar receiving s-yvtemic
Co'rt iссЙЙ! го id 5 for treatment of lupus erylhemaLos-ut-
D-F: liil.ilt'r.i! mull i foe a! RPL idelachitflents surm unded by
fibrinous sutjrelinal ejfc-JidaLe in a pn(iun-! receiving s-ytlemic
corli costeroid lifiatmenl tor lupus crylbemalosus.
G-l: БЛа1егд1 mu hi focal К HE detachments and subrelinai
fibrin in a w om an receiving systemic corticosleroid treat­
ment for r»odular fasciilis.
I—L: This wom an w ilh a fr-year history of conlinuouH pred­
nisone therapy for lupus erythematosus anti Sjogren's syn­
drome developed L'xudalive delachment o f the rigEi-L m dtula
associated w ith multiple terous RKE detachments (arrows^
Htibrt'tiriHil sefofibrii>cius relinal detachmeh^ and a pig­
ment epiLheliopalhy resembling lilndus flavimaculatus ir>
her ri цп I eye. Her Iell eye had been cmuc lu lled following
ftB y S jm o rta i endupbthalmilis. Two years previously' sbe bad
mullipJe amputations* of lhe J inhere ai>d bolh I идя (J h. Laser
pboloooagulation- of the RFL delachmontH failed to Mpduc^j
resolution o f lhe macular detachment. There was progression
ot" lhe pigment epilheliopalEiy lo involve most of lhe tundus
(I). Angiography revealed a leopard-spot pa Hern o i non fluo­
rescence and mu hi pie focal sites of leakage1 throughout Ihe
posterior fundus IL !. Note perHslcnl areas of RPE delachmenl
(anowsl.
of the RFt: detach ment. Ihose wilh recurrent detachment
may show extensive atrophy of the ЙРЕ throughout lhe
central maculararea.
'l'he long-term visual prognosis for most patients with
ICSC is good. Approximately 20-30% of palienls will have
one or more recurrences.1,1 ir' Although approx­
imately one-lhird of patients will have biomicroscopic and
angiographic evidence of one or more focal changes in the
ЙРЕ in the opposite eye; fewer than 20% are destined lo
develop serous detach ment of the macula in the opposile
eye. Evidence to dale suggests that only a small percentage,
probably less than 5%, of these patients will ever develop
choroidal neovascularization or chronic detachment with
cystoid macular edema. H'_
Pathology and Pathogenesis
Ihere is limited Inform atjijil concerning the pathology
of EC5C [Figures 3.3 2 and 3.13). Histopathologic e lim i­
nation of one eye obtained from a palienl who died of
a myocardial infarction showed no abnormaEily in lhe
choriocapi Haris underlying lhe RPE detachment (figure
З Л З ].1Ш l)r. de Venecia found no definite abnormality in
the choriocapi Haris in lhe cast’ occurring in lhe patient
wilh chronic renal failure previously cited (E-igure 3.]2J.C'1'
] Lis finding, however, th□L the gray-while exudate noted
clinically contained fibrin provides evidence thal a marked
alteration occurring in the permeability of the choriocap-
illaris bad permitted escape of serum proteins as large as
fibrinogen, '['his while serofibrinous subretinal exuda­
tion occurs in the area of RPH detachment in 10-15% of
all palients ivith [C!sC.-J I his observation, together with
other features of I CSC, including (he frequent hlisler-
Eilie detachmetil of the lit31: underlying the serous retinal
detachment and the frequent presence of large amounts
of subretinal fiuEdr is further evidence that increase in the
permeability of lhe choriocapillaris is the primaiy cause of
damage to the overlying RPt, focal loss of the RPE attach­
ment lo liruch's membrane. ,md movement of plasma
proteins and water into the subretinal space in palients
wilh ICSC Endocyanine green videoangiography
has provided additional evidence of abnormal chorio­
capil la ry permeability that may be more exlensive than
that indicated by fluorescein angiography.| :: iuL; ipiiznas
has suggested (hat a reversal of direction of ion secre­
tion by the focally damaged RPE allows water to move
toward the retina rather than the choroid. lw Marmor
postulates that patients With [CSC must have a in ore dif­
fuse area of metabolic impairment of the RPli to explain
3,1 j Bilatera I se rofi bri n(j u s retinal p igmen t e pi lhe Irum
(RPE) and bulk)lis relinal detachment occurring
fn patients receiving renal dialysis and after renal
transplantation,
A—D; Л 3 7-yea r-ol d К a Live Am erican wuman Heceiivirg renal
rl Jjil у his deveiofjed bilateral Serotibrirfous retinal detachment.
She had w e ll-controlled hypertension. .Note Lhe fibrin envel­
oping Ihe EiE’b delachmunlf- (arrows, A <tnd №.. Angiograms (C
and I J j show m ulliple RP£ delachm cnls in righleye.
E—H: Inferior hi Ia Lera I bullous detachment in a 40-year-ald
N alive Am erican man 1 inonlh after receiving a renal trans­
plant. H e was receiving systemic corticosteroids and antt-
meLalioliles. Н ет had woll-conLroMed hypertension. Note
w hile fibrinous exudalion surrounding R P t delnchmenls
farrows, E and J- . Angiography revealed "ктокеы чк к" leaks
from [he a№as of PPE detachment. Nine days later he devel­
oped rapid loss of vision in Lhe left eye. W ilh in 4 weeks
visual loss p repressed vo по I i^l it percept ion. Computed
tomography repealed evidence o f I hie keninjj ot' the Irtfl
oplic nerve And orb i la I Гissue. The lelE eye was enucleated.
HistopalEmlo^ic exam ina I ion revealed fifjrinous exudate in
the sub-KPE space farrows}' and subretinal space l-CJ and H !■.
N o definite pathologic changes in Ihe choriocapillaris were
identified. Separate LLssue removed from Lhe orbital apex
reve-ided aspergillosis erf Ihe optic nerve and orfiil.
il-Hjm dt Vertec ti ,L' i
the detachment that may persist for Weeks or months.H*
there is experimental evidence that a focal injury to the
choriocapi I Lary wall as well as the RPE may be impor­
tant in the pathogenesis of I CSC. Kl<’ '['he pathogenesis of
1CSC and the mechanisms explaining bow pholocoagu-
ialion accelerates resolution of relinal detach men L are
unclear.UlJ,2ftEC)7,lCj,J-]Ll
88 ' • ■] ! : А Diseases C ausing Hxudative and H em orrh agic Detachm ent
Allhough palients with ECSC typically have no systemic
disease.. they often are highly competitive and compulsive
workaholics who relate the onset of I heir symptoms Lo
unusual stress, such as a change in job. demanding dead­
lines, marital problems, family death or sickness, or acci­
dental injury'. I4 JLJ-!|J Yannim i has demonstrated a high
association of type A behavior pattern in patients with
ICSC compared lo control groups of palients.' 1^ t here is
no convincing evidence that ICSC is either infectious or
inflammatory in naturell£’ or that it represents a diffuse
RPb dystrophy.:s
A picture similar to ICSC has been produced experi­
mentally by intrasderal injection of indomethacin in
rabbits, and by repealed intravenous administration of
epinephrine in monkeys and rabbits.11" 1'' This work
Lends credence to lhe iheory lhal stress may play an impor­
tant role in causing focal perinea bilily changes in lhe cho-
liocapilEaris and loss of adherence of the RPh to Bruch's
membrane in palients who are predisposed lo macular
delachmenl. 'l'he observations lhal: (1) syslemic cortico­
steroid adm ini st rat ion may precipitate and aggravate ICSC;
(2) patients with Cushing's disease may develop [CSC; and
(3) pregnant women show a predilection for developing
ICSC suggest lhal elevated serum cortisol levels may be of
importance in the pathogenesis d f ^ C . * a 5Ml
There is some evidence to suggest that the prevalence
and severity of ICSC are related lo race. ICSC- along wilh
mosl olher disorders associated wilh exudative detach­
ment of the macula, occurs infrequently in black persons.
ICSC occurs commonly in Latins. Orientals, Asian Indians
and Caucasians. The severe recurrent form of the disease
may be more common in the Latin population.. Asian
Indians, and in Orientals.
3.13 H isto path oEogy of id iopa thie cen tra I se rous
ch ori oret inopathy,.
A: Hislopalhology of slto us detachm enI of iht1 retinal pig-
mL'iiI epilhulium (btlJ Lj (m d retina in a 52-yBSir-ald man W ho
died iiecaune cjt acute toronary thrombosis. lbi? palirnl
apparently had no visual cum plaints. The delachm enl was
found on rouline examination (И Lhe eye at aulopby. .Mute
E illd a tiV ^ detachment ol the macula. The choroid Lind pig­
ment ер Иhelium w ere normal.
B: Serial sections. through the macula revealed a small area
of serous duJachment ot tiic KFJb beneath lhe peripheral pari
df lhe ddachrnent (arrow). The underlying chorfaxapf [laris
was normal.
С—H i Probable idiopaLhic central serous cboriorelinopathy
occurring in a (/.t-year-o Id man who developed j lar^e area
of serous retinal detachment of lhe left Гйасщй -^mall art0 Ws;
Q . Superiorly there was subrelinal wbilish-gray exudate
fiaryo arrow, C j that bicicked fluorescence early л i>d stained
Late angjo^rapbica 11у (arrow, D;. There were scattered dru­
sen in Ibe peripheral fundus bu 1 only a few in lhe m acular
areas. The relina] detachmcml resolved spontaneously w ithin
several months. F-eur years laler his visual acuily was 20/20,
righl eye, and 20/25, left eye, jus I before his dealb as a res all
ul com plications of Laryngeal surgery. Hislopalhological
Examination revealed a small focus ш lype I sub-Rl^E neo­
vascularization benealb one drusen in ibe righL тасиЗд
(see Figure ЭЛ Й ) and in Ihe juxtapapi ilai v region of ibe lefl
oplic disc I hi.. In ibe area of fluorescein leakage in the lefl
eye ih eie was а focal loss of lhe relinal recepLors and K P t
ft:. Tbc lL:i lined K PL was irregularly tfevaled |jy a defiosil of
I'os-niipiiili; b . period it acid Sthiff-poSibiire \ . | j i i ъ;:|м-
lunyslic acid-positive :Сj I т а Le rial w ilh a fine fimshiike pat­
tern, suggesting lhal Ihe auEi-K^E material included fibrin. In
Ihis area I here wa.i some m ira tio n of RPEi cells inlo Ibe sub­
relinal space farrows, Ь and FL
Differential Diagnosis
Giber diseases that may cause localized serous detach­
ment of lhe Dijcubl include; ( 1 ) congenital pi I of the
optic nerve; ( 2) choroidal lumore. located in either the
macula or periphery] areas, particularly superiorly, for
example, hemangiomas, metastatic carcinoma, leukemia,
melanoma, and osteoma; [3} retinal hole in either the
macula or paramacular area of patients with high myo­
pia with posterior staphylomata or in the peripheral fun­
dus superiorly; (3) malignant hypertension, toxemia of
pregnancy, collagen vasculaF diseases, or other diseases
associated with D \C; [5] choroidal inflammatory diseases,
either focal, for example, presumed ocular histoplasmo­
sis or sarcoidosis, or diffuse, for example, Harada's dis­
ease, sympathetic ophthalmia, benign reactive lymphoid
hypeiplasia of the uveal lractr and posterior scleritis; ( 6)
idiopathic uveal effusion; (7) ocular contusion; (S ) trac-
Lion maculopalhy caused by incomplete posterior vitre­
ous separation; and [9] senile macular degeneration and
idiopathic polypoidal choroidal vasculopalhy (1PCV).
Long-standing interior peripheral exudative retinal detach­
ment in patients with chronic ICSC may be mistaken for
retinoschisis, uveal effusion, rhegmalogenous detachment,
or L-ales' disease if the patients develop Fetinilis proliferans
and retinal capi]lary closure in (he area of chronic retinal
iffiaachirient*4,<9 (See discussion of atypical presentations
of I CSC.) In patients older than 50 years of age and with
a few small drusen in the macula, or in palients with one
or two small chorioretinal scars, it may be impossible lo
exclude senile macular degeneration in the former and
Lhe presumed ocular histoplasmosis syndrome (l]OJ-i5j in
the latter as the cause of the serous macular delachment.
In such cases there is a greater risk that the focal leak may
represent a small neovascular complex rather than a serous
detachment of die ftPE. Jn some cases the association of a
systemic disease with serous macular detachment may be
coincidental.123
Patients loll owing scleral buckling procedures in the
early postoperative course may have one or more round
or oval areas of exudative relinal detach menl that simulate
serous detachments of the P P t in the macula (see l;igure
7.29C-1).
Treatment
'Ihere is no evidence that medical treatment, abstinence
from smoking, or the administration of beta-blockers has
proved useful in the treatment of [CSC.ljN Ihere is good
evidence that photocoagulation of the site of JtPL delach­
ment or the RPli leak produces resolution of the retinal
detachment usually within 3-4 weeks in mosl of these
patients (Kigure 3 04D _[}jiU ‘t.J7J4&rSO.8WDDJ96rHii25-us
There is no evidence, however, that prompl pholocoagufa-
Iton reduces the chances of permanent loss of visual func­
tion.-' 4 «.эцш л** There is no value of placement of
photocoagulation into areas other than those showing evi­
dence of leakage angiographically.IUJi- 1" 11'
Although lhe complications of photocoagulation, such
as accidental coagulation of the foveola, retinal distortion,
and choroidal neovascularization,; 14 are few, it is
probably iiot advisable to recommend immediate photo­
coagulation treatment in all of these patients. The follow­
ing criteria for photocoagulation are utilized by Cass:
■ Allow A months for spontaneous resolution if the
patient has had no previous history or ophthalmoscopic
evidence of previous detach menl.
* Wait 6 months or longer before photocoagulation if the
RPE leak is less than one-founh disc diameter from the
fovea.
■ Allow 1 month for spontaneous resolution in palients
with a history of several episodes of delachment in the
same eye, if after each episode the palienl has regained
normal macular function.
■ When the leak is al least one-fourth disc diameter from
the center of Lhe fovea, prompt photocoagulation is jus­
tified: ( ] } if detachment has been present for 4 monlhs
or longer; {2 ) if lhe patient has evidence of permanent
loss of acuity or paracentral visual field in either eye sec­
ondary to previous episodes of detachment; or [ 3] if for
occupational reasons the patienl cannot work because
of the visual dysfunction caused by the detach menl.
Lighl- to moderate-intensity applications of all modali­
ties of photocoagulation including argon, krypton, and
dye laser photocoagulation to lhe area of RPIi. detachment
or RPE leakage are effective in treating [CSC.j:
Laser debridement of Lhe Ki^E an Lhe area of lhe leakager
permitting ingrowth of surrounding RPE, is probably all
that es required to cause resolution of the detachment
(Figures 3.05 and 3.t)9A-F).':" : i2 It is importanL to look
for m y of the biotJUCroicopk: or angiographic signs of
choroidal neovascularization when evaluating Llie leak­
ing area in these patients. M iniffial-intensity photocoag­
ulation applications of a size tailored to Lhe area of RPE
delachmenl should be used. If there is any evidence to
suggest the leak may be caused by choroidal neovascular­
ization., Lhen more intense treat men Lis indicated. Even in
cases where no evidence of neovascularization is evidentr
probably of Lbese palienLs w ill develop evidence
of choroidal neovascularization within several weeks or
months of treatment.1 "1-0"' This is one of the most
important complications occurring after photocoagula­
tion in these patients. En some, iL is probably caused by
the treatment, and in others, il may exist before treat­
ment. Careful monitoring of the size of the treatment
scotoma on the Amsler grid by Lbe patient after treatment
is important in the early detection and treat ment of this
coLnplicalion.
Chronic and Recurrent IC S C
Lowering of discontinuing systemic steroids in those
receiving steroids should be tried as the first step. Failure
of resolution of fluid should prompt light focal laser to
the leaks (Figure 3.05J if demonstrated on an angiogram.
In those eyes with widespread chorioretinal involvement
as seen on fluorescein or indocyanine green angiography,
photodynamic therapy' is beneficial in most cases.л:>
Both full- and reduced-fluence treatments and full- and
ha If-dose have been used; more recently reduced flue nee
has been advocated to Feduce toxic effects of the therapy,
l'he spot size is determined by the area of staining on the
angiograms. Лп extra 50Q-|im zone is not necessary, as in
treating choroidal neovascularization, Care must be taken
Lo avoid including the foveal center if no significant sub fo­
vea I Hu id is present.
|ampol eL a!.1'' have shown resolution of subreLinal
fluid by (he use of mifepristone, an anliglucocorLicoid and
antiprogesterone medication used as an aborlifacienl. A
daily dose of 200 mg caused dramatic resolution of subrel-
inal fluid, but it recurred once the drug was discontinued,
l’he drug works by blocking Lhe glucocorticoid recep­
tors via negative-feedback control of adrenocorticotropic
hormone and cortisol, causing an increase of both in the
serum.
AG E-RELATED M A C U L A R 3.14 Ту pi cal o r еки dat 1ve d ru se n .

D E G E N E R A T IO N * A -С: Macular, peripapillary, and peripheral drusen in a

AMD is a chronic degenerative оr dystrophic disease affect­
ing primarily the cboriocapiHaris. Bruch's membrane, and
the ftP t.160' 1' ' It is the commonest cause of legal blind­
ness En the USA and UK. 'lhe large number of names used
in lhe old literature to describe the various stages of the
disorder have served lo obscure the fact that it is probably
a single disease LhaL in many cases is familial and inherited
as an autosomal-dominant trait,176 " " Site presently most
widely accepted name, age-related macular degeneration,
is unfortunate in some respects because it suggests lhal all
affected palienls are elderly and lhal its root cause is aging.
Although the average age of patients when they lose cen­
tral vision in the first eye is 65 years of age. some patients
develop evidence of the disease in lhe fourth and fifth
decades of life. As of 2004, it was eslimaLed lhal about 3
million individuals are affected by AMD in the USA and
1.75 million of them have advanced disease.'141 it mostly
24-year-fjld Шчэп with 2iV20 visual acuily in both eyes (A .
An^iojjiamH showed hyperfIUoresceri spots corresponding
w ilh dru^cn iВ and С ) .
D -F: M u hi pie variably sized dtustm in a 4 2 -уел r-old man
w ilh 2 & 2 0 visual acui’ v-
G-l: Confluence o f multiple brge drusen in л frfl-year-old
man. Nole lhe irregular paJlurn of Ыа ininjj erf lhe larger dru­
sen cenlm]ly. Visual acuily Was 2CH'&0.
1: Schem atic diagram showing variatiu-ns in Ihe ГСиосевсеп!
pa Item uf e'tudjilive drusen in w hich Ihe relinal pigmenl opi-
Iheliuin basemen) membrane fbm, arrajwl is of normal
or near normal thickness. Black dols represent fTuotescein
molecules. A hyalinizod drusen i l l may transrnil the inLra-
choroidal fluorescence because of thinning of Ihe overlying
FiF’t but may be sullicieiuiv dense lhal diffusion c l dye across
Bruch's membrane IBM inlo the виЬ-ЙРЁ material does nol
occur. In Lhe case of drusen w ilh Iели dense material benealh
lhe К RE i.2, .31, Jhe dye may diffuse- inlo lbe sub-KF’b malerial
anti cause inLe-nsafication of fluorescence of Che drusen dur­
ing the laler slaves of angici’Taphy.

affecls white blue-eyed individuals and es rarely respon­

sible for visual loss in black persons. I',', AMD should be
distinguished from lhe following diseases: (1] dominantly
inherited progressive juvenile fovea I dystrophy associ­
ated with drusenlike changes and macular staphyloma, a
disease that is endemic in western North Carolina (see p.
296J; \2) basal laminar drusen and macular degeneration
(see p. 132); and (3) pattern dystrophy (see Chapter 5).

'A lso known as senile macular degeneration, senii-c macular

fhoroid.il dcgeneraliion, senile disciform macular degeneration.
Ejjhnt-|unLus disciform dedchm ent, la mi I ial drusen, dom inantly
In h erit'd druseп, I lotchinson-Tays central guilaLe choroiditis,
Doyne’s honeycombed choroi Jitis, and ] lobhouse-Balten super-
Hciat choroiditis.
Prediscrform Stage
Typical of iE xudative Drusen
The earliest sign of AMD is the development of multiple,
usually discrete, round, slightly elevated, variably sized,
sub-RPL deposits in the macula and elsewhere in the fun­
dus of both eyes (f igures 3.14-3.16). 16r,_ш These deposits
□re called drusen. l'he German word лdruse" (plumI "dru­
sen") means nodule, referring in particular to areas of clear
crystallization within stones, 'l'he term "typical" or "exu­
dative1 ' drusen is used here lo differentiate these variably
sized deposits of extracellular material lying between the
basement membrane of the RPE and the inner collagenous
zone of ttruch's membrane from uniformly smalt, round.,
nodular thickenings of the RPE basemenl membrane
(basal laminar drusen, cuticular drusen J thal probably
have a different pathogenesis (see p. 132). '] у pica L or exu­
dative drusen may develop in early adulthood but infre­
quently are visible biomicroscopically until middle life or
later, ta lly in their development drusen may he inappar-
enl ophlhatmoscopicafly because of their smalE size and
relatively norma! overlying ftpji Usually, however, ihey
can be detected in retroillumination wilh the slit lamp as
semi translucent bodies.
As the deposit enlarges and lhe overlying RPEi thins,
druseii assume a yellow or gray color and are more eas­
ily detected. They vary widely in size from yellow punc­
tate nodules ( 1 'hardT drusen; Eigure 3.14A) to large, pale
yellow or gray-white, placoid or dome-shaped structures
indistinguishable from localized serous detachments of
the ЙРЕ ( uso fr drusen: Figures 3.14D and G and 3.15A).
Drusen are often clustered in the macular or paramacu-
Ear area. Whether centrally or eccentrically located, iheir
distribution is usually symmetric in both eyes n 13rusen
change in size- shape, dislribution, color, and cons isle псу
wilh the passing years (Figure 3.1 Although they
tend to increase in number and size [Figure 3.1 SC and D),
drusen may also fade from view and decrease in number
(Figure 3.1SA and El). In some cases, areas of geographic
atrophy of the pigrnenl epithelium may remain follow­
ing disappearance of drusen (Figure 3.15F and I-'). Drusen
may become calcified and crystalline in appearance (ilgure
3.15A. and see Figure 3.2У). 'Ihis change suggests dehydra­
tion of the drusen and often precedes lhe development
of geographic atrophy of the jftPE.. Occasionally drusen
develop a polychromatic or golden sparkling appear­
ance indicative of cholesterol deposits. Some drusen may
become ossified and assume a while appearance. A few
may appear pink secondary to choroidal neovascular tufts
growing through Bruch's membrane into the drusen. In
some palients the sub-ISP F deposits are distributed dif­
fusely rather than focally and are evident ophthalmoscopi­
cally onlv as an ill-defined area of slighlly mottled yellow
color of (he KPF in the macula.
3.15 Natural course of lypical (exudative) drusen,
A And B: .VlulLipk1 Iа где drusen, same o f which are con Пи-
m l, in а 65-yuar-old wom an w ilb a visual ist.uity o f 20/40.
Several drusen are pnrlly calcifiw J [аптлуа* A). Sam e palicml
4 years taler L3J shoWirlg fading and disappearance o f dru-
sen. VitUiiI acuity wan still 2ti'40.
С лгн! D: Note lhe? сЬапце in distribulion. sJiape, and size
□I the drusen in this 73-year-old palienl over a period of
3 years. Visual aciilty in С was 20/25 and in D was 20 "^0.
E and f: This 73-year-old patient developed multiple local
areas of geographic atrophy o i the retinal pigjnenL epithelium
fK P tj over a period of 2 years. Her initial visual acuity was
20/30. Her visual ncufoy w hen Iasi Mien :H was 21^40.
C - L : Prtjyression of large drusen to "drusenoi d" К PE detach­
ments of lhe К PE Narrows, I and Ll in a 67-yuar-o]d wom an.
Lelt eye, July 1Э в Ы С ) , April 1991 (H), February 1S93 (la n d
I). Right eye, July 1986fEQ, and February 1 9 H {L}.
Most patients with the predisci form stage of lhe dis­
ease have excel Lent visual acuity and are asymptomatic.
Soane With many drusen centralLy complain of decreased
ability lo read, particularly in dimmed illumination, and
mild metamorphopsia. I.oss of contrast sensitivity is com­
mon and may be out o f proportion lo loss of Snellen acu-
jty |oss тЛ у ihe entire macula and is
nol confined to lhe areas with d r u s e n .F a rly loss of sen­
sitivity may be a predictor of severe visual loss.-™ Patients
frequently experience difficulty with driving an automo­
bile al night. Eilectrophysiologic tests in most patients are
normal.-41" Some may have mild to moderate reduction
in eleclro-oculograpliic responses.
Drusen are nol always confined lo lhe macular area. In
some patients they may be present nasal lo the optic disc.
In others they may be largely confined lo lhe peripheral
macular area, particularly in the areas of the major vascu­
lar arcades. Drusen in this latter distribution may have a
somewhat granular, less discrete appearance and may be
seen in bEack palients, who infrequently deveEop drusen in
the macular area.-31' Many widely scattered drusen are usu­
ally visible with a three-mirror gonioprism in lhe periph­
eral fundus. In contrast to drusen in die posterior pole,
ihese drusen often have a haEo of pigment al their base.
In some palients these drusen are arranged in a conflu­
ent, linear, and triradiale pattern to produce a prominent
pigmenied network visible ophthalmoscopically in the
mtdperiphery of the fundus [Erigure 3. J 7J . Ih is is. usually
most evident nasally and is referred lo as senile reticular
pigmentary degeneration.j9L-2Lj-2Lji A narrow, indistinct,
yellow or gray zone caused by the deposition of sub-KE’Ei
drusen material often surrounds the temporal ha!for more
of the opLic disc.
■-ЧЙ
 Patients with multiple large drusen and with focal areas
of hyperpigmenlatLon in the macular area are at greater
risk of developing sub retinal neovascularization.^'^ ■'''12''
J'luorescein angiographic findings in drusen are variable
anti depend upon their size, height, degree of pigmen­
tation of lhe RPE on their surface, and the contents and
coEtsislency of the material lying between the ЙРЕ and
Bruch's membrane. Most (Ш е л cause focal well-defined
hyperfluorescence. The time of appearance of their early
fluorescence depends upon the rale of staining of Bruch's
membrane and the sub-RPE material, and (heir trans-
lucency. lhe intensity of their laler staining with fluores­
cein depends primarily on their consistency (hgure 3.14),
Although a delay in ihe appearance of the background
choroidal fluorescence occurs in some patients with dru­
sen, it is probable that this is caused by a delay in stain­
ing of Bruch's membrane and Lhe sub-PE1E: materia I, both
of which in some patients may have a higher lipid content,
rather than a delay in perfusion of Lhe choroidal blood
vessels."1" " ' Smaller Liodutar ("hard"} drusen typically
show a peak fluorescence wiLhin several minutes of injec­
tion, and fading paralleling that of the background cho­
roidal fluorescence. Ruorescence of medium and large
drusen may he delayed until Lhe later stages of angiogra­
phy (figure 3.14G-JJ. Ihis may be caused by the thickness
of the drusen as welt as the Jipid content of the drusen and
the underlying Bruch's membrane {E'igure 3.14G-J).22b
Angiography may reveal Lhe presence of more drusen than
are apparent ophthalmoscopically.
IILstopalhologically, most drusen consist of focal col­
lections of eosinophilic material lying between the base­
ment membrane of the РЕЧ;! and Bruch's membrane (E'igure
3 l6 j 1 й ^ !и&23г-2зэ 1Ъеу th e re in represent focal
detachments of the RPE\. ihe detached RPE cells may be
thinned and hypopigmenled. The sub-RPli material may
appear homogeneous and hyalinLted (E'igure 3.16A), finely
granular [E'igure ЗЛ6В), or a combination ofboLh (E'igure
3 J6 C ).'' En some cases it may contain calcium, cho­
lesterol clefts, and bone [Figure 3. !6L>).-jr,2W>Jh e variable
histopathologic appearance and composition of drusen
suggest that their consistency probably varies from watery
or mushy in the case of the large placoid drusen [E'igure
3.1GB], Lo farm in the case of the nodular hyalinLaed peri­
od ic acid-Schiff (PAS)-positive drusen (i'igure 3.I6A}, lo
hard in the case of calcified or ossified white drusen (E'igure
3. ] C15).|,J |[ ihese histopathologic variations I hat
have given rise Lo physicians' use of lhe terms "hard'" and
'soft1' to describe lhe clinical appearance of small, discrete
and Eargerr often placoid drusen, respectively.
As mighl be expected from the variability of Lhe clinical
and histopathologic appearance of drusen, there is hetero­
geneity in regard to their ultrastruclural and histochemi­
ca I makeup. There is evidence in monkeys and humans
that Lhe earliest development of some druseLi involves the
outward evagi nation of portions of the basal cell wall and
cytoplasm of the RI3Ei cell into the sub-RPh space beuveen
3.16 Morphologic variations of typical or exudative
drusen.
A: .VlulLiple hyafinized ^ ш т " nodular сНгиьитк
В: Granular "safl" drusen.
C: Com bined granular and hyaliniaeij drusefi (ahnow).
D: C alcified "crystalline" drusen. Nate new vessel larrup
henealh Lhe relinal pigrriint epithelium.
E: Diffuse deposition of granular drusen malerial ipnt)baE)3y
both basal lamina* unci basal linear deposits I in m acular
aJ6a. Note lo ta Г calcificaLion (arrows^ o f Bruch's membrane,
widening of Lhe falercatti hLry- pillars df Ihe t htjriuciapillafis.,
find partial obiLrucliijn of Lhe <horiocapilfaris.
F: Е х Ь з Ш с И Ш ife a of ьагггй eye. NuLe rel a Lively normal
Knrth's memE>rane and choriocapi I lari*.
the inner collagenous portion of Bruch's membrane and
the RPE celE.'"'--'*'1" 3^ 'Ibese vesicles of cytoplasm become
pinched off, degetierate, and form a nidus for the accu­
mulation of an admixture of metabolic products and sub­
stances derived from the surrounding RE4i, retina, and
choriocapi Haris tlislochemical and electron microscopic
studies of typical or exudative drusen reveal a variety of
substances and materials accumulating between Lhe rela­
tively normal basement membrane of Lhe detached RL’El
and the inner collagenous zone of Bruch's membrane.
These include sulfated and nonsulfated glycoconjugaLes;
lipid material; plasma membranelike material; vesicles;
amorphous material: types I, [EE. IV, and V collagen; ftbro-
nectin: imLTtunoglobulins; degenerated PPE organelles;
and viable cell processes.'',l}-'И - - ^ М Я | Some inves­
tigators have allribuled these viable cell processes sur­
rounded by basement membrane Lo macrophages, or
pericytes, rather than RPK cells.' |:'
1EtslopathologicaiJy there may be minimal degen­
eration of the relinal receptor elements overlying drusen.
Many eyes with focal drusen show, in addition, a thin
layer of fine granular eosinophilic materia! separating
the RETL from Bruch's membrane throughout most of the
macular region [figure 3.16b). Llltrastructurally ihis sub-
PL3E: deposit may lie between the RPE plasma membrane
and its basement membrane (basal laminar deposit) or
between Lhe inner collagenous zone of Ekuch's membrane
and Lhe basement membrane of the RIT: (basal linear dep
ositJ.L'jr-' 'ihe basal laminar deposit is com­
posed primarily of wide-spaced collagen;: the basal linear
deposit is composed of vesicular and granular electron-
dense. lipid-rich material. Some authors believe lhal basal
laminar deposit, which is primarily type IV collagen, is a
unique feature found in eyes predisposed to the develop­
ment of whereas others have prescnLed
evidence lhal il, along With the thickening of Bruch's
membrane and drusen, is an aging change and is nol
ULtique for A M U " '6,11' Both types of deposit are particu­
larly noticeable in eyes with multiple large so-called ^soft”
drusen and disciform detachments.■'|J
H fW s
 Other important histopathologic changes in lhe macula 3.17 Peripheral senile reticular pigmentary
accompany dniS^ 1w^ 23JJ3 ia ^ i53 There is in s u ­ ctegeneralion.
lar thickening and Lhinning of Bruch's membrane associ­ A-F: M acular drusen.. choroidal neova scuJari/aLion „
ated wilh calcific degeneration of the elastic and collagen ar?d peripheral reticular pigmentary deyenemtidfi iA - C .
tissue comprising this 5[ШС|иГе.2Я>':г3|'23?':г‘1б'-24' ,-:*‘| \n ihe Angiogr.iphv i j. v ( :--:! !od .'. I ri radiate pa1lern ; i |ji.-i i : :-ln:-i -; dn:-
underlying choriocapillaris there is thickening and hya- sen aL Lhe equator puriрзЬеги11■ , D-F-..
linizatioti of the intercapillary stromal pillars second аry G-l: N ate the peripheral drusen and pigment changes in
Lo lhe deposition of a PAS-posttiw material that effec­ Lhj* /.‘i-year-old man whose eye was enu Sea led beta use of
a small malignanl melanoma of Lhe choroid. Angiography
tively reduces the surface area oi' the capillary bed (I'igure
showed evidence df mu Hi pie drusen- and irregular loss oi pig­
З Л б Е ) ^ 00,231,1" lhe large choroidal vessels are unaffected.
ment from I ht1-relinal pigment epi I helium iHI3t.: (JI'j. Note Lhe
Ihere is no indocyanine green angiographic or rheologic reEicuiar partem cl nonfluorescenL pigmenl. H islcpalhulogic
evidence of impaired choroidal perfusion in patients with seel it >n ot С showed multiple drusen irregular thinning til Lhe
drusen.",|J''1, 'Ihe changes in Bruch's membrane and the RPE, and clumps a J large pigjnenL-laden cells (arrawr I}. The
choriocapillaris that accompany macular drusen have been retina i.nol shown) showtid mild Joss of Lhe receptor elemenls.
referred to previously as senile macular choroidal degen- I and K: Peripheral cross-hatch-1 ike pi^ n en t changes of
senile rt.4i-CLil-jsr pigment degeneration show up an Iiiradiate
eration.J' 0 It is uncertain., however, whether these changes
hyperauLol'luorescent changes.
are manifestations of a dominantly inherited dystrophy or
are merely degenerative changes secondary to aging. iCj-l ln>m Cjjii

I listopat biologically, a few scattered drusen are found fre­

quently in the peripheral fundus, particularly in the ag^ngeye
of white p a tie n ts.W h e n numerous they are arranged in a
reticular pattern and are associated with hyperplasia of Lhe p. 27Й), North Carolina fundus dystrophy (see p. 296),
iiS>L between drusen that produces a reticular pattern of pig­ fundus albi punctate dystrophy [see p. 326), Alport's dis­
mentation ophthalmoscopically Lhat may be mistaken cli ni- ease [see p. 316)r and ring-17 chromosome ret inopal hy
cally for that in retinitis pigmentosa (I'igure 3. J 7).jL|u J i (see p. 320). in monkeys and humans focal lipidization
In ail, ЯО-УО^ЬоГ patients with many peripheral drusen show of RPE cel3s may cause fundus lesions that resemble small
evidence of age-related macular changes. ''" drusen. ihese pun elate, yellow lesions usually are
'ihe pathogenesis of typical or exudative drusen is not evidenL angiographically. A few of them are often
unknown. Although most recent authors have favored the found in the central macular area of otherwise normal
view lhat aging or dystrophic changes in the RPL are primar­ fundi in adults of all ages, '['heir pathogenesis and their
ily responsible for the accumulation of abnormal material relationship to drusen formation are unknown.
beneath its basement membrane, it is uncertain whether the lhe primary cause of significant loss of central
primary locus of lhe disease resides in one o ra combination vision in paLients with AMD is serous and hemorrhagic
of Lhe retina and RPI., Bruch's membrane- or choriocapil- detachment of the RPE and retina caused by choroidal
^ demonstration of iteovascula rizat ion.
viable cell processes within drusen in their early develop­
ment" and Lhe later finding of incompletely digesLed O ccu lt C horoidal N eovascularization
RPL and relinal cell organelles within the sub-RPL material l'he ingrowth of new vessels exlending from the cho­
suggest Lhat the posterior evagination of buds of tift: cell roid into the sub-RE*h space In one or more areas occurs
hasal cytoplasm and basement membrane is an impor­ frequently and is the most important histopathologic
tant slage in the development of change lhal predisposes patients with drusen to macu­
Accumulation of lipids in ttmch's membrane is part of the lar delachment and toss of central vision [see discus­
agjng process of Bruch's membrane and makes il Lo some sion of type I choroidal neovascularization in CJhapler
degree a hydrophobic barrier lo the movement of water 2y^ijQ0№iit,2UMV.25ijA3.277-2S4 Neovascular buds
and ions toward lhe choroid. ''' ■''' 'Ihis may be an impor­ invade and penetrate the degenerated Bruch's membrane
tant factor in fostering enlargement of drusen (conversion and proliferate beneath the RP1: [figures 2.05-2.07 and
from hard to sofl dm sen), and confluence of drusen Lo form З л а ).162-255"™ In addition, capillaries may invade the
serous detachments of the pigment epithelium.'l'SJ£<’"3|,'i' " 1 sub-RPJ: drusenlike deposits adjacent Lo the oplic disc by
Although there is much evidence lo suggest that typical or extension through or around the edge of Bruch's mem­
exudative drusen may be inherited as an autosomal-domi- brane (figure ЗЛвО).-4^ ■'■ Et is not known whelher
Eiant characteristic the role of heredity in the causation of the granulomatous inflammatory response to degen­
drusen in most patients is uncertain.17 - Drusen erated Hruch's membrane found in some cases is an
have been produced experimentally in animals with intravit- important factor in the process of subretinal neovascu­
real injection of aminoglycosides."73 larization 24!>-JSil-
29a The accumulation of phospholipid-
Other retinal flecks that may clinically simulate dru­ containing membranes in the outer collagenous zone
sen include those occurring in patients with cuticular or of Bruch's membrane and of lipid within drusen may be
basal laminar drusen (see p. 132), blargardt's disease (see responsible for attracting these macrophages.-""1
 ]?ie new capillaries that penetrate bruch's membrane
grow in з Hat tanwhed or seafan configuration away from
their site of entту into the sub-RJ^E space (see I'igure 2.07).
l'he retinal blood flow in these vessels initially is slow and
the integrity of the capillary endoLhelium is adequate Lo
prevent ejtudalion (I'igure 3.JdJi). In some causes Lhe slow
proliferation of new vessels and fibroblastic prolifera­
tion may produce a solid election of the ЮРЕ (see Figure
2.QG). Jhese organized RTE detachments or mounds may
vary in size and shape and are often irregular in elevation
(see figure Э.22А and D}. because the fine biomicroscopic
details of the elevated j^FE arid drusen look much the
same as the surrounding RPE, arid because of the minimal
angiographic changes in the area of these organized RPE
mounds, they may be easily overlooked wiLboul careful
contact lens examination and good-qualily stereoscopic
fluorescein angiograms. Occasionally these organized
EPE detachments may assume tumor!ike proportions and
simulate choroidal hemangiomas clinically (see figure
3 2flEj. Failure to recognize areas of organized RJ4L detach­
ment adjacent to areas of bigh-flow choroidal neovas-
cular membranes (C.NV.Vis) or adjacent lo large serous
detachments of lhe RPE is responsible for many of the
poor results of photocoagulation.■'■'' "" ™ The structure
and function of the RPE and relina overlying these occult
CNVMs or mound5 may be m inim ally affected (figure
ЗЛ В). During tltis occult stage of choroidal neovascular­
ization Lhe patienl is usually asymp to malic and the new
vessels may not be apparent either ophthalmoscopically
or angiographically.'''' Ihe stimulus causing neovascular
invasion of lhe sub-KPk space and the explanation for its
more frequent occurrence near the center of the macula
and the peripapillary region is unknown. The histopatho­
logic observation of choriocapillary atrophy in the vicin­
ity of neovascular ingrowth suggests that ischemia may
be an important faclor. Екрет| menially, lype Jl sub retina!
3. IS Occult choroidal neovascularization in pa Lien Is
with drusen.
A—D: This 69-year-old man with a fe(w drusen Jarr-ows, Af
in lhe m acula ul Die ri^ht eve presented with и large serous
deLat/hnnenl of Ihe le lim in Ihe тлей la Ы the left eye (see
FJauie 3 . 1 0 ) . H e died o f com pficaJions Ы Laryngeal surgLwy
and teriaH sections of lh e right m acula nL lhe site erf one dru-
sth ikffnporalmost a n o w in Al revealed sis nuund break? ir>
Bruch's membrane. Through each о I Ihese breaks passed
a small capillary tuft inom Ihe t boriocapillaris into Lhe sub-
nerinal pigment epithelium (RPE) space (bihiws, E and C).
Simiilar sub-RPE capillary lufts were found beneath Lhe Lem-
poial margin or lhe -right oplic disc ^rrow , D).
E: Large sub-Rf-’t o c tu ll qid fn ida! neovasculai memEjrane
(CNVYvt; anowsl. N o le relalively normal R P t and relina as
well -as absence of exudation.
: I: f r o m (.Jr c u n .in d К и у .- 1 1 ■
choroidal neovascularization can be produced by photo­
coagulation damage to the choriocapillaris-Bruch's mem­
brane-liJ’li com plex.'" '''! '['here is no experimental
model for Lype I sub-Rl'J- choroidal neovascularization
that occurs in AM IX
D isciform D etachm ent Stages
Although mosl patients with A M I) are in their seventh
decade at the Lime of onset of symptoms, loss of acuity
in some patients may occur in the fifth decade or earlier.
Significant loss oJ' centra I vision in ihese patienls occurs
primarily by three mechanisms: ( J) confluence of drusen
lo form multilobulated exudative К PL detachments (5 %
or fewer of cases); (2) geographic alrophy of the RPE and
retina (5-10%); and (3) subnetEnal neovascularization
wilh serous and hemorrhagic detach menl of lhe R P t and
retm a{Sp-3tm }^*,ai,1^ J313S730S-111
A g ^ -R e l a t e d . Л 1 л т а 1 п г D t 'f i c m 'T f i i u w I О I
Exudative D etachm ent o f the Retinal Pigm ent
Epithelium U nassociated with Choroidal
N eovascularization (Avascuiar Serous RPE
D etachm enti
Unlike palienls wilh ]CSCr patients with drusen infrequently
develop large лгеля of serous retinal detach ment overling
small w iuui &PE detachments, but they frequently present
with large serous НРЁ detachments and minimal serous reti­
nal detachment (figures 2.04.. 2.09. and 3. i cJ}. Ibe normal
aging changes in the inner zones of Elrucb's membrane as
wnell as those lhal may be peculiar Lo AMD cause loosening
of lhe adherence of the RPK basement membrane to Bruch's
membrane. Increased lEpidizatLon of Enoch's membrane
renders it hydrophobic and л barrier to normal movement
of fluid by the ИРЁ inlo the choroid.- -1- 1 ]his predisposes
patients with AMD Lo the formation of soft dmsen and lo
progressive enlargement and confluence of drusen lo form a
focaE area of tit11: detachment, oflen with scalloped borders,
a slightly irregular surface, and a LriradiaLe patlern of orange
or gray pigmentation on its surface. 'Ihese avascular КГЧ-
detachments, referred to by some as drusenoid RPE detach­
ments, typically develop slowly and initially may cause mini­
mal complaints of blurring and melamorphopsia (E:igures
3.34C-I and J3.1Eit’r—L.). Angjograpby in these slowly devel-
opiLig avascular serous RPE: detach men Ls shows a gradual
staining of the suh-RHiexudale and oullines the nonfluores-
cent pLgmenl figure on its surface figures 3.141 [ and ] and
3.151). Ihere may be some irregularity of the Eale staining
pattern caused by irregular density of the sub-RPL material.
A few palients may experience abrupt visual loss and distor­
tion caused by a more rapidly developing, round or oval.,
smooth-surfaced, dome-shaped area of serous detachment
of the RE11-. in the absence of any evidence of occult neovas­
cularization (ligure 3.iyA-L>). These rapidly developing
avascular RPE detachments show a patlern of rapid even
fluorescein staining ( E'igure 3.1УЕ) lhal is unlike lhal seen
With most serous PPL detachments caused by choroidal neo-
vascularizali on (see discussion of vascularized RPE: detach­
ments. p. 106) as welt as ihose lesions that may simulate
3;19 Serous detachment of the relinal pig men I
epithelium (RPEj in palienls with age-related macuEar
degeneration.
A —D : This &4-year-old man experienced lEie unset of me)a-
morpbopsia in the li^Hl Hffift; Visual acuity was 20/3 О. Л
sen ju s; dc>1acE:menL of Ihe KI-’E was bresenL iА.. Liru-sen wtjfe
present in Lhe lelt m acula. Angiography revealed rapid, even
Rlainini; o f Lht1 Alb-RPE uxudaLe IB . I'he dark zone centrally
is. caused E)y Lhe ielin;il лшиЕюрЬу]!. Arj^on laser appii(.alions
were p Jic e d slraddlinu. lht1 rffergin of lhe FiF’i: delaC^irriertt
(Q . N in e months lalet (Ew detachment had resolved 1U>.
Visual acuity was 20/30.
f and F: A bO-yuar-old wom an w ilb serous d d o i^ n e n l of
Ihe FIL’fc ■arrows, t:-. O n e monlh afLef ruby laser Lreatmenl lo
Lhe margins of Lhe.1 KF’t delnchmcnl. ii had resoked (FK Visual
acuity was 2ft'40.
G: HisLopalhology of serous. de4achmenl of Lhe RPE in a
бй-year-old wom an w ilh m acular drusen. This lesion was
misdiagnosed as a malignitnl moliirmma. Arrow indiciiles
small drusen LhaL aie detached ^lon^ w ilh lEw KKL:. iub-KPb
exudate extends ihruujjh a small rhidfftrip in the RPL inLu Ihe
subretinal $pace пеаНЬк- lefL w id p t LEie photomicrograph.
|C j i г и т 2з1.Ы ii i A n > t r i [ . in M e d i c a l . ' V i a u L i . j I i o i ' i . A l l r i^ h t i
n.^ervi.'d.j
serous RPE: detachment, such as metastatic carcinoma, amet-
anotic melanomas, or other solid tumors.
Because of prognostic and therapeutic implications, It
is important lo look for signs of choroidal neovascular­
ization. ivhich usually is the cause of ihese rapidly devel­
oping detachments of the RPIi.-1 " 'L'be vision of palients
wilh subfovea I serous RPE detachments can usually be
corrected Lo 20;'25-20,'40 with the addition of plus lenses.
When Lhe re is no choroidal neovascularization there may
be only minimal progression of visunil loss over many
months or years. The detach menl may enlarge slowly and
occasionally may spontaneously flatten. 'I'he value of pho-
locoagulalion (i-'igure 3. P JJ is uncertain.*30'-^'1H9_1J4
Serous and H em orrhagic D etachm ent o f the
Retina C aused by C horoidal N eovascularization
Al any stage In the development of an occult CNVM
beneath the RPhlv blooci flow may become sufficient to
cause leakage of serous exudate and diapedesis of red
cells inlo lhe subpigment space around lhe CNVM. This
may progress to produce a variety of ophthalmoscopic
pictures of exudative and hemorrhagic delachmenl of
the macula. The mosl frequent sequence of events giving
rise lo symptoms is the decompensation of the RPE over­
lying the CNVM and serous delachmenl of the overlying
and surrounding relina (Kigure 3.20). A light-grayish dis-
coloralion usual]y occurs in lhe area of lhe CNVM. ihe
blood vessels comprising lhe CNVM may or may not be
visible biomicroscopicalEy (Kigure 3.20J. Small foci of sub-
relinal blood or yellowr lipid-rich exudate may occur near
the margins of the CNVM. In cases where the neovascu-
Ear membrane extends beneath the retinal capillary-free
zone, cystoid macular edema may occur, ihe reasons for
the accumulation of inlrarelinal exudate in this instance
are uncertain, but it may be caused in part by disruption
of the relinal outer limiting membrane-receplor cell bar­
rier lo the inlrarelinal migration of subretinal e\udale
and the paucity of the relinaL capillaries in ihis area lo
remove il [see Kigure 2.15 and discussion in Chapter 2).
'Jhe ability of" stereoscopic fluorescein angiography to
Localize a CNVM accurately depends primarily on the rale
of blood flow through the membrane and the presence or
absence of materia! anterior to the membrane lhal may
obstruct the view of the fluorescence within the capillary
network.1
The typical cartwheel or sea fan pattern of the new ves­
sels is visible in high-flow membranes wilh minimal
exlravasated blood, cloudy exudale, or fibrous tissue ante­
rior to il (figure 3.20). in some membranes with only a
3.2il Sub-retinal pigment epithelium {RPE)
neovascularization in patients with drusen,
A —£ : This t'kk'tly woman torn pi л i nod of mikl blurring (if
vision. The new-vessel (Yiembifene -was Lintel у obscured by
the grayish-yellow ex.udat£ lartipwsi in the sub-Hi1! space (A .
A few red capillaries were visible near Lbe upper margin of
Ifie membrane. Note dye peri using the sub-KPt vessel н lhal
were arrangec- in a seatan pattern :K rand C). The dye leaked
from these vessels and stained lhe surrounding exudale in
the sub-hi PE нрасе.
D and E: Another parent w ilb choroidal neovascularization
it.1l. Angiogram shtywed seafan configuration of new vessels (El.
F: Large chcxcridal nwivascular membrane (arTdWs] thaL
extended ibrougb break in Brush's membrane I ell iiniiw'i.
moderate blood flow rate, an ill-defined ooze of fluores­
cein appears late in the area of the membrane (Figure
3 . 2 ! When the serous retinal delachmenl ts caused by
leakage of exudate from the surface of an occult sub-I? I1!:
neovascular complex, angiography may show only a mul­
tifocal pinpoint or irregular pattern of staining al the sur­
face of the organized ]?PL detachmenL (}:igure 3.22ft and
С).114 л35-52й-3-' ihe accurate localization of choroidal neo­
vascularization in such cases \ч difficult, tl is also difficult
or impossible if part of the CNVM is obscured by blood
located beneath either the RPE or the retina. Stereoscopic
angiograms are essential to Lhe delection and localization
of mosl CNVKis, particularly lhal pan of the CNVM com­
plex lhal is occull. Areas of irregular elevation of the № £
that do not slain probably harbor occult new vessels. Once
exudation begins, mosl CNVMs progressively enlarge lo
\ - l disc diameters in size or larger and cause progressive
loss of visual function.
Serous D etachm ent o f the Retinal
Pigm ent Epithelium C aused by C horoidal
N eovascularization ( Vascularized RPE
D etachm ent)
!n patients with AMDj acute visual loss is caused by a
Eaige.. sharp] у circumscribed, smooth-surfaced, serous
delachmenl of the RPH in approximately 10% of rases.-11,
in the majority of cases, ill is detachment is caused by cho­
roidal neovascuEarizationJ3'*30,255--*26--350 Because of the
cartwheel orseafan pattern of sub-RPH CNV.V1 and because
of the relatively firm connection established between the
new capillaries and the base of the overlying ftPE, there
es a predilection for serous exudation and/or hemor­
rhage to occur near the margin of the GNVM. I his results
In detachment of the adjacent RPE around the margin
of the CWyM, and production of a variety of shapes of
Eaige RETE detachments [see figures 2.05, 2.10, 3.21 r and
3.22).1011 If the detachment occurs at one segment of the
edge of the CNVM, a flat-sided, reniform, or notched RPh
detachment is the result (Figures 3.2! and 3 .2 2 ).^ If the
detachment extends away from the entire margin of the
CNVM, a doughnut-shaped RPH delachmenl may occur.
Any of these irregularly shaped RPH detachments should
suggest the probable presence of a CNVM thal for the
most part lies outside the area of RPH detachment, within
either the notch or the central depressed area of lhe RPH
detachment (Mgures 3.21 and 3.22J. Uiomicroscopically
there may or may not be any other evidence of the pres­
ence of the CNVM in these areas, ff serous detachment
of the RE’ti overlying the CNVKl occurs, a round or ova!.,
dome-shaped detachment identical lo an avascular RPH
detachment may resulL. If serous detachment of the RPH
develops adjacent to an organised sub-RPK. detachment.
3.2 E Notched serous detachments of the relinal
pigment epithelium (R P E ) caused by choroidal
neovascu la rizati on .
A-^F: A ^ f- y e a td d w o n u n w iIh an RPE dclitchmenL tiils e d
by two qCO jIl choroidal neovascular membranes (C W V M s;
arrows.. ( I i w ithin nol t hud zones IA I. ^lureoscopit. view of
lhe late angiogram and 0 and early алдю ^гит ( Dj. Агдот
faser treatment was applied to the tw o neovascular mem­
branes, and two focal laser Ь ш ш were placed at the 4 :i0
marjj.il? of the RF’ L tJetachfiierl : Ы . Tw elve days later the fet-
ina and К H1!: w ore reallached iF-.. StibnetihS blood was Я е ь -
ervt at lhe sites of ph otocoa^Lil a ILon of (he C N V M k .
G - L : A 56-yea.r-oid man with a lar^e ftPE detachment. dark
fluid level (small л now. G), and nolch [large HtTow, Cl . ii>t
months laler lhe h?l-'Ei detachment was larger (H). N:(Hc slow
slainin^ of suIj-RF3E fluid, nonfluoiescenl fluid level, and late
fluorescein slaming in Ihe area of the notch 4j. anowsl. Argon
laser treatmenl was pfjated along' the margin of the delach-
ment and at 1hE!- site о I occult neovascularization ^ЩгаwJ К .
Note dark blood dial appeared j u M above reW-vesseJ mem­
brane fa n o w i during ifeatm&Ht. F4jur weeks laler Ihe relinal
and H.F’1: deLachmenls had resolved 'L.i. Visual acuity was
2 0/40.
an irregularly elevated, oval or dumbbell-shaped RPE
delachmenl develops (figures 3.22Л-С and 3.23A). lhe
details of lhe RE*L and drusen are better preserved in Lhe
less-elevated, orga ni/jed part of the detachment [['igure
3.22D). The presence of a dark meniscus [blood or blood
pigment) at the dependent part of the serous RPL detach­
ment (Figure 3.21 G J or of subrelinal blood or yellow exu­
date near its margin is evidence of the presence of a CNVM
located either just outside of the edge of. or benealh, the
(£№ detachment.
 The fluorescein aLtgiographic findings art important in
differentiating vascularized from nonvascularized serous
KPE detachments.'1)5,29Э In vascularized serous RPH detach­
ments, lhe sub-RPt exudate usually stains more slowly.
presumably because of the presence of a large amount
of protein and blood pigment within the exudate, and
incompletely because of an uneven distribution of blood
or a mound of fibrovascular tissue present beneath the
RPE detachmenl { Figures 3.21 and 3.22). When a serous
RPH detachment arises at one edge of either a Elat or ele­
vated organEzed CMVM, angiography often shows early
fluorescein staining of the sub-RPK serous exudate in
the area of serous detachment but delayed and uneven
or, occasionally, no staining in the area of the CNVM. In
st)me cases, however there may be an intensification of
Lhe staining of the sub-RPli exudate adjacent lo the CNVM
(E'igure 3.21 E). When exudaLe from Lhe CNVM detaches the
overlying as well as adjacent RE*K lo produce a round or
oval detachmentr slow or uneven staining of the sub-RPH
exudaLe in the area of Lhe neovascular complex may be the
only clue lo lhe presence of Lhe underlying CN VM
Serous RPK detach me nls caused by choroidal neovas­
cularization are likely lo be large, lo develop evidence of
hemorrhage and organization [sub-RTE; fibrovascular pro­
liferation], and to cause significant loss o£' central vision
soon after onset of symptoms. tJecause portions of the
CEWM are Liearly always bidden from view beneath the
RPE detachmenl. treatment wilh pholocoaguEalion is dif­
ficult and of uncertain
Retinal Pigm ent Epithelial Tear
PalienLs who develop a serous RPK detachment extend­
ing away from one pari of an organized RP11 detachment
are at some risk of developing an Rl’E: tear spontane­
ously, during or following pbotocoagulalion, and even
following anli-VHCK therapy (Eigures З.ЕУС, 3.22, and
3.J2J5J 1 Typical pretear findings are: [ ]) a
Eaige, round, oval, or slightly dumbbell-shaped elevation
of the RPE with one area less elevaled Lhan the other; (2)
preservation of the RE4i details, including drusen in the
smaller, less elevaled. organized ponion of the RfE! eleva-
Lion: and (3) irregular and incomplete fluorescein staining
in the area of less elevation, and delayed bul even more
intense staining of (he sub-RPK exudate in the more ele­
vated serous portion of the RPH detachmenl (figures 3.22
and. 3.23 J^-363311 ЧЪеге may be no other biomicroscopic
signs of underlying choroidal neovascularization. hither
spontaneously or following l realm ent, ati acute R L1Ь. I ear
may occur at or along the border of the serous RPH detach­
ment on the side opposite the location of the new ves­
sels. These patients usually notice an abrupt increase in
vLsuat Eoss caused by the passage of serous exudation from
beneath Lhe RPH inlo the suhreLinal space. Occasionally,
however, patients may retain excellent visual acuity in
spile of extension of lhe rip tjenealh the fovea] center
$.22 Pa rtly organ ize d ret iпа I p igmen t e priht Iin m
( R P E ) detachments.
A-K: Two notched serous H.5J t d e ta c b liric ^ surround my an
elevaled □rgaftiJSefcl detachmcnL. The lafler stained iiruj'-
ulaKy w ilh fluoresceitl i'hS, slereor arrows'.
С—H : K PE tear occurring in partly organized serous RPE
deLnchmeril i.n лп ftS-year-old man. NoLe drusen and bijj-
menE epithelial m a rk in g evident overlying nasal organized
half of R I’E delachmenl I arrows, O . h'ole uneven and incom ­
plete sLainin^ of nasal part of dolnchmenl (D and El.
Several i^ e k s Eater a leaf has occLfeed alon^, thy lemporal
ivuirqin of lh<- deLachmenl (FJ. The edge of the tear has curled
under and retracted nasally against Lhe organized parL o f tFie
deLachmenl iarrow). ^ngiogtapEry showed minimal slaining
wiLhin lhe fj igmenled mound, ] п-cdic-iatijn^ presence erf chonui:-
dal new vessels (□). Severaf weeks later there was subretinal
bleeding from lh e choroidal new vessels w ithin lhe pig­
mented anound I arrows.. Hi.
RPE tear posllreatment with ranrbizumab,
[—L Ttii5 65-year-old wom an w ilh a strong fam ily history of
age-reEated m acular degeneration developed a fibrovascu­
lar pigmenL epithelial deta ih m ел I Lhat was asymptomatic
and found during EDllow-up of caLaracl s-игэдегу. She received
inliavitrea] ran ibiz L im a Ej and noted dislorlion al vision aE'ler
Lhe second injection. Л tear in the h!L3L was found -:ind Eier
vision had dropped to 20/40, quickly worsening to 2(1/400 in
3 weeks due to further retraction of Lhe pigmenl epithelium
(K). hour years later a large disciform scar with chronic sub-
rdinal fluid anti blood in I ho E"ve could Ere гееп.
(E'igure 3.23.Д-Н E. and Only if seen within 14
hours after the tear w ill the free edge of lhe RPE be seen
before iL rolls under and retracts toward the area of sub-
retinal neovascular tissue.
by the time most patients present there is a crescenl-
sbaped geographic zone of absent RPE adjacent lo an ele-
vaLed hyperp igmen ted mound composed of the retracted
and rolled-under RPK collapsed against the surface of lhe
fibrovascular tissue (E'igures 3.22ti and K). ]he retinal
delachment resolves soon afLer development of the tear,
presumably because of regrowlh of hypopLgmenled RL]Ei
cells across the defect and perhaps also because of partial
closure of the choriocapillaris (figures 3.22 and 3.23).
In some palients this nets growth of RPH is visible bLo­
rn Ecroscopically as a blunting of the edges of the tear by
ingrowth of a faintly opaque layer of tissue inlo the area of
lhe tear. In some cases a prominent layer of fibrous meta-
plaslic RPK grows iLilo and obliterates evidence of Lhe tear.
Subretinal blood and lipid exudate frequently appear sooli
after development of the tear. Angiography done after the
tear usually shows evidence of early non fluorescence and
mottled late staining in the area of the retracted and orga­
nized RPE mound, as well as marked diffuse early and late
hypertluorescence in the area of absent or bypop igmen Led
RPE and staining of any subretinal fluid Lhat Ls present
(figure 3.22).
 I Loskin and associates’41 suggested Lhat lhe prelear
picture was best explained by separation of lhe RPti from
its basement membrane in lhe area of maximum eleva­
tion, predisposing il lo lear. '['his explanation, however,
is Linlikely because of lhe light adhesion of ihe К 14: Iri
its basemenl membrane in normal as well as pathologic
conditions/’" and because it does not explain the clini­
cal and angiographic findings lhal suggest that under­
lying choroidal neovascularization is the primary cause of
both the pretear and posttear appearance.1^ Chuang and
Bird"270 and LSLrd and Marshall"' 1 have stressed the itnpor-
tance of lhe hydrophobic nature of the lipidized Bruch's
membrane acting as a barrier Lo passage to fluid into lhe
choroid in the pathogenesis of Jt[TE tears in pal Lents wilh
AMD, 'Ihe hiomicroscopic and angiographic findings,
however, strongly suggest dial hydrostatic pressure gen­
erated by leakage of exudate from the margin of occult
suh-RIT new vessels is lhe primary precipitating cause of
mosl of the targe, smoolh-surfaced, bLister]Lke serous RPE
detachments as well as the acute ЕЖЁ tears that occur in
patients with AMD {Hgure ^ G Q jj,338*350 Occasionally.
however, rents developing in lhe thinned RPE at the edge
of long-sLanding avascular serous RPE detachmenLs are
responsible for their spontaneous collapse. L’atienls with
Large KPb lears associated with А Ш ) are at high risk of
developing RP!i tears in the fellow eye.11'
i.2 J Retinal pigment epithelium (RPE) lears in
patients with age-re Ialed macular degeneration,
A—F: This 59-year-old w om an developed melamorpbapsia
in Ihe LefL eye. Arrowheads indicate angiographic evidence
Lit' parity urbanized portion o i a bilobate hiKL rfefechmenl
IA and В in April ]№ 4 . K'ole delay in complete staining
o i the infenonnsal pari of lhe KF’b delachmenl I stereoscopic
view s E and Q . In M ay Э984 she developed a rip in the (IPE
lhal eslended benealh lhe cun lei of (he fovea ( 0 Jind ste­
reoscopic view s E and FI. Two months later, in spile of lhe
5и Ь fayeaI rip anti serous detachment of lhe relina, iior visual
ncuilv corrected lo 2CV2(). Ten months I a lor the acLiilv was
reduced lo 20/20Q.
G : Diagram showing palhogcnesis or KF’b lear. iilflge E,
Organi^Sd RPE delachmenl (anow j. ila g e 2 , Serous delach-
ment of lhe adjacent КГЕ. Stage Tear in Ihe FiPE and serous
delachmenl of Ihe felina. SLajje 4. l-ree edi^e of lorn K P t
ha ы го i leLl Lowaitl fib ru v a s ^ iu l tissue and non pigmenled
К F’f: has j^rown across Ihe defect, caLising resolution o f lhe
serous retinal detachment that occurred follow ing the tear.
Fir, rulinal receptors; ИРЕ, retinal piijjmejit epithelium: cc,
l horiocapil laris.
H -K : This -year-old male oeVelatoed an HfJb delachm enl
w ilh subretinal and intrarelinal fluid in his left eye (H). A rip
occurred alter bis scscond intravitreaS ranibiiLimaEj injecttpn
bul Ihe vision remained at 20/40 tlj. A vertical set lion on
oplical coherence tomography reveals lbe dinconlinuily of
Ifie pigmenl epi I helium ,|- and 'h e dark гопе bereft of RF3!
on «Lilofluorescunce lmaf’inj' |Kj.
I A —I- l y jm j p r e it n lc d at H u n r m ^ i n (Jlu b M t je L in ;; N u w jr ilK ir 1 1 , 1 Ч Я - J: G
\к>т iGjii.™)
 S’ags t -accuh rfiovaECjIarizElnn

Staoe 2 - s e ra L -s d e L a c h T e n l r i RPz

S la g e 1- R F £ Lear and r&iinar dalacfinneiL

(Gj SLaoe 4 - r E s a lu t a n c f reLnal dEtachm Enl

 Angiographic evidence of microrips at the edge of
smaller RPh detachments, wilh streaming of fluores­
cein dye inlo the subrelinal space similar to that seen in
palients with ICSC, occasionally occurs in patients with
A M D ,ЮС1'3’ ^ Likewise, large lU’L tears similar to those asso­
ciated wilh AMD occasionally occur in otherwise healthy
palients with ICSC with large, often multifocal sero­
fibrinous RPE detachments, and in palients with systemic
Lupus ery(hemalosus and the same findings (figure 3 .30).
Ihe R]’K tears in these patients are presumably caused by
hydrostatic pressure generated by severe focal damage lo
[he permeability of lhe choriocapillaris (see discussion in
earlier section on [CSC).
'lears in lhe RPE may occur along the juncture of fibro­
vascular elevation of Lhe RPH and serous RE’K delachmenl
during applications of pholocoagulation to the neovascu­
larization.’" ' 11' Ihese tears occur most frequently during
treatment of hypopigmentedr thick sub reLina! neovascu-
lar membranes wilh krypton red laser and are caused by
contraction of the fibrovascular tissue comprising lhe
membrane.
Radiating C horioretinal Folds Surrounding Partly
O rganized RPE D etachm ents
Spontaneous contraction of lhe fibrovascular tissue oflen
hidden beneath serous Rl^K detachments may pucker
BrndVs membrane and cause a series of radiating chorio­
retinal folds around the base of the ftFB detachment (see
Ttgure 4.04 j/ ''1The radial pattern of yellow rays seen oph-
tbalmoscopically and the hyperiluorescenl rays seen angi-
ographically are produced by the linear ridges of infolding
of the RE>K and choroEd. 'L'his pattern of folds may be the
on!y ophthalmoscopic sign of occult choroidal neovas­
cularization detectable in some patients with large serous
detachments of the RPE. ll is curious that this radiating
detachment stages
3.^4 H e m o r r h a g i c d is c if o r m
occurring in p a t ie n ts with drusen.
A find B: Hemcurhagic deLHthmenL in ,i 6fl-y war-old mar:
w ilh drusen. Mosl of lhe blued fs in № JAibrettnij ap ate
and was derived from a chofuidal nuavasLiilar т е ш Ь м п е in
the papitlum acular bundle region Narrows, A). Visual acuity
in Lhis- eye was 2li',30. There $afi bponlantious resolution of
Hubrt'tmal blood and return of visua! acuiLy Lo 20/25. li ^ a t
La ken J уеат* nfler A.
С And 3J: SpiWilanscHbls resolution of 1лгде? bkat к fumiorrha^Jc
deladm ienl езг" retina] pi^mL'nl opilhe I i шп :К HE: i and relina
ft". The disciform scjar ;Dl extended lo lhe interior edjje of
the foveal center.
E and F: This palienl was referred for te^itment of ,i chtftriJda.)
melanoma. The irregular brown i:olor change in Ihe sub-KPt
and ijLJbretinaj hlood w a s responsible for Ibe misdiagnosis.
Angiography showed no evid en ce of fluorescence within the
lesion IFF.
G : Large hemorrhagic deLachmenl ol the EiFE in я patient
with macular dmsen. Bleeding occurred from new vessels
lyin^ beneath Ihe Rh3E (arrow).
Il-гит Cuss.1
' *-'i
pattern of folds does not {Jtcur more often in response
lo pholocoagulation of CNY.V1. Jhe forces producing this
radiating pa item of chorioretinal Id Ids are similar lo those
responsible for a fmer pattern of superficial inner retinal
folds radiating outward from a contracted epi relina I fibro-
cellular membrane.
Linear C horioretinal Folds A sso cia ted with
O rganized RPF D etachm ents
A series of slightly irregular chorioretinal folds may
develop on the surface of organized ftPE detachments If
the superficial portion of the sub-JtfTEi fibrovascular tissue
undergoes shrinkage.1"'"
H em orrhagic D etachm ent o f the RPE and Retina
Bid d ing from the margin of a CNVM may hf mild and
cause only mild blurring of vision. Spontaneous rupture
of a blood vessel usually near one margin of a GNVM,
however, may cause sudden loss of centra I vision second­
ary lo a large hemorrhagic detachment of the RPH and ret­
ina [Rgures. 1.24 and 1.25).-1X1 Initially lhe blood may be
confined to the sub-RPr space and ophtbalmoscopically
may cause a dark, almost black.- discretely elevated mound
beneath the relina. Drusen are often evident on the surface
of this mound. Al the time of the hemorrhage or within
a few days or Weeks lhe blood dissecls through lhe edge
of lhe RPfc detachment and spreads lit a shallow layer inlo
Lhe subretinal space, where it often appears as a reddish
halo al the margin of the RPE detachment (figure 3.2-1).
Ih e dark appearance of blood beneath the RPE is caused
by the mound I ike collection of blood and nol by its mere
presence beneath the RPb. The reddish appeanmce of lhe
surrounding subretinal blood is caused by lhe absence
of the tillering effect of the RPI: but also by lhe thinness
of the layer of blood. Large mounds of blood, whether
benealh the RPt! or the relina or within the vitreous cav­
ity, often have a black appearaEtce. Ш a few paltents dur­
ing the early weeks after lhe bleeding episode there may be
remarkable retention of visual function in spite of a large
subfovea] hematoma.
3.2 j S e v e re in tra o c u la r h e m o rrh a g e c a u s e d b y age-
re la te d m a c u la r d e g e n e r a tio n (A M O ),
Л-E: Th rue monlhs SHtejJ a large hemorrhagic detachment «I
Lhe №titi9 itntl retinal piemen L epithelium (ИРЕ) 'rV m tine I el I
eye, ihis elderly' man relumed with blood slaining Of lh e vit­
reous ■;Lii and irih (arrow. Cl. O ver a fa-mo nth period Ihe vilre-
ous cleared and lhe iris relum ed lo ils normal blue color :□ .
А 1ат^е disciform scnir Wnis prusenl in lhe macula it).
F: Secondary subretinal hemorrhage occurring at the tem pe­
ra] edj*eof a disciform scar. Compare w ilh f.
G and H: Extensive subretinaF, suprachorordal, and inLravrLreal
bleed ing occurring spontaneously in Ihe lelt eye at ап eEderly
p.11i-f.-n". wiLb A M D and л disciform lesion in (he righl eye.
I: .Missive Subretinal and inlravilreal hemorrhage caiised by
bleeding from л tocal area of sub-RL3E. neovasc/ulafizalion in
Lhe m acular area lanowj.. This occurred in a Ьб-year-old man
With esisenlial 1турег1*ьпнюгт, chronic lytnphaQc leukemfa,
and drusen in lhe m acula of lbe opfiosile eye.
1: Secondary sub-RPE hemorrh.ige oct uning al lhe lempo-
ral margin df ал old disciform scar larrowi in Ihe macula of
an elderly patient w hose eye was misdiagnosed as having a
rnaligtpani melanoma o f the chom id.
■
i i ,1. im
11and J Imm Cab. :
 Lrlood in lhe subrelinal and sub-RPL space typically
obscures completely lhe underlying choroidal fluorescence
and most or л!Е of lhe fluorescein leaking from lhe neo-
vascular complex [ I'igure 3.24). lhe absence of subretinal
Lluorescence serves let differentiate a da_tk mound of blood
from a choroidal melanoma, which aIways shows evidence
of tale slain ing because of blood vessels near its surface
(E'igure 3.24L and f-'). Once bleeding occurs in the sub-
RFE space, varying degrees of organization of the blood
occur and Lhere is usually extensive degeneration of both
the overlying pigment epithelium and reLina. Conversely,
blood present in lhe subrelinal. space may reabsorb com­
pletely wilh variable and oflen minimal permanent dam­
age to the structure and function of the overlying retina
(I'igure 3.24A and
Many palients who develop large hemorrhagic macular
detachments will experience transient loss of peripheral
vision lhal in mosl cases is caused by diffusion of hemo­
globin, raLher than whole blood, inlo the vitreous sev­
eral weeks or months after the hemorrhagic detachment
occurs.Jlll) The fundus may be completely obscured from
view for many months (Figure 3.2 6A-li). I his process of
anterior diffusion of hemoglobin across the relatively
inlacl retina after damage to the outer harrier structures
of the retina by lhe sub retina! blood is similar to lhal
which occurs in some patients after a massive hyphema
with hemoglobin diffusing across damaged corneal endo­
thelium and Descemel's membrane to cause blood stain­
ing of the cornea. The breakdown products of blood may
stain nol only the vitreous but also the iris stroma. "I"his.
causes a yeilow-brfiftv§ discoloration of the vitreous and a
noticeable heterochromia in lightly pigmenled individuals
(i'igure 3.26В and C). Usually after 3-6 monlhs or longer,
as lhe blood pigment is phagocytosed, the iris regains ils
normal color, the vitreous clears, and lhe peripheral vision
3.26 Massive exudative and hemorrhagic detachment
of the retinal pigment epithelium iRPEj and
retina caused by pre-equatorral type 1sub-К PE
n eovasc u la rizati on.
A-С: Thi н S3 -yea r-ol d wom an w ilh RtaicuJdr drusen devel­
oped loss of central vision bilaterally because o f posterior
extension o f subrelinal lipid exudation arising in a large
peripheral exudative and hemorrhagic: subreLinat neovascular
complex i A яп-d В I. Laser photocoagulalion and transsdeial
cryopoxv went successful In destroying Ihe new vessels and
causing resolution of lhe suhmacular exudation i.C..
D-F: Multiple areas qf peripheral hemorrhagic delachmenl
of the RF’b and retina in Lin й7-year-old man wilh minimal
evidence of macular degeneration.
G - J: Hislopalhologic findings in an elderly wom an w h o ini-
liiillv had Lhe same ofjtilhajmoscopic findings seen in D-I-.
bhe developed massive sub-Fi^L-. subrotinal, and vilTeous hem­
orrhage ust before death w hile in Ihe hospital. Arrow fC> indi­
cates Hite of Hutj-HE’t nuovascular network and hrmiorrhage.
Hleedrn^ from a neovascular network lying alonj; the inner
side o f Bruch's гп е тЫ а п е iwhile arrows, Hi пелг the equa-
lor was rcsponsjhle for Lhe humorrhagjic del.ichmenl of the
K.PE: (black and white Arrows}. MoLe ruyjlure of blood vessels
in Sub-ftPf! neovascular nelwork if)Lick arrows, t) internal lo
KrudVs membrane (white amow№ | shows suh-RPL neovascu-
far network tf>lack arrows! on lhe inner surface of the Bruch's
membrane fw+iile arrows;- in anolher птеа oi lhe same eye.
returns. I’oor central vision and a large disciform scar are
usually the end result (I'igure 3.2(Sh). In elderly palients
presenting wilh inlravitreat blood. AMD should always
be considered as a possible c a u s e .- 15S-r,:' Lvidence of
AML> in the opposite eye is an important clue to the cor­
rect diagnosis. Ultrasonographic demonstration of a mass
of variable reflectivity in Lhe macular area of these patients
is helpful in excluding so me of lhe other causes of vitreous
hemorrhage
 In patienls With moderate lo lar^e areas of hemorrhagic
detachment of the JIETE and retina, photocoagulation
is often not effective because lhe blood obscures at least
p.irt of the CNVM from view, [n caws where the bleeding
appears to have occurred from one edge of the CNVM and
where the configuration of lhe CNVM suggests lhal il does
nol ел Lend far beneath lhe blood, photocoagulation of lhe
CNVM with a loiig-ivavelenglh laser may be of some value.
C hronic Exudative and H em orrhagic Stages
Once the process of exudation and hemorrhage begins...
the CNVM usually continues to enlarge, often in a concen­
tric manner. Oozing of blood cells from the outer dilated
margin of the CNVM occurs frequently and is responsible
for the fecks of subretinal blood thal may intermittently
appear at its margins (E'igure 3.27A). I'he dark irregular
areas often seen angiographically aL the edge of these sub-
ttFE membrane^ even in lhe absence of biomicroscopic
evidence of blood, are probably caused by breakdown
products of blood accumulating ihere. The yd low exudate
that occurs in the outer retinal layers and subretinal space
peripheral to the area of choroidal neovascularization
is caused by precipitation of the lipid component of the
exudate as water is drawn into the norma E blood vessels
of lhe retina and choroid (see pp. 46-47). ihe expand­
ing neovascular complex causes nutritional damage lo the
outer layers of lhe overlying retina, and once the mem­
brane has grown beneath Lhe center of the fovea, loss of
useful central vision is usual, bul nol always a certainty.
Involution of this neovascular process may occur aL any
stage of ils development and typically occurs Within sev­
eral years. Approximately 70% of eyes thal develop detach­
ment caused by a CNVM extending into the capillary-free
zone of lhe retina will haw a visual acuLly of 2G/200 or
Eess within 1 year.1^
Cicatricial Stage
Involution of the neovascular complex eventually occurs
and is associated with varying degrees of subrelinal scar
tissue, depending primarily on the duration and extent of
hemorrhage and exudation [figure 3.27). Jn some cases,
neovascularization extending throughout Lhe macula
may be associated with minimal reactive hyperplasia and
fibrous metaplasia of the RPf. and the laq;e neovascular
membrane after Involution may be difficult or impos­
sible lo demonstrate biomicroscopically or angiographi-
cally. In some cases the larger radial vascular trunks of the
involuted membranes may be visible as red vessels super­
imposed over the usually partly yellow-colored larger cho­
roidal vessels [ELgure 3.27D-E-). ihe slow rale of blood
flow in these involuted neovascular membranes may pre­
vent (heir demonstration angiographically. Angiography
may demonstrate nothing more than a circular area of
mottled or early hyper fluorescence and minimal or no
3.Z7 Reparative and cicatricial stages of disciform
macular detachmenl in patients with drusen.
A: Partial resolution of hemorrhagic detachment of Lhe reLi-
i .11 pigment epithelium IК PL '■ iind retina. Note evidence of
i If'L'M! .Hii i 1 ( i Iho blood I у i г»ц bcNiealh lhe KJ'I m i rt v.'s..
Thy re has btton ]il1le change in Ihe subfeLinal blood lhal sur­
rounds the ftPlE detach mu nL (нее С:.
В: IbrLiy organized, piymenLecf subrtHinal disciform mass
(arraWjjJ stimulating a melanoma.
Lar^e, white fibrovascular disci form scar with rel iгьосЕю-
roidal anastomosis (arrow).
D-F: B,l alend palcEuv nibrous p n o l i f c - M l io n and d iff L is e a t r o -
pEiy of the r m iiT a l pigment epithelium w i L h enlracellula-r pig­
ment dum ps (t J a n d Ё). The auto f l u o r e s c e n c e image le v e a lj
Lhe diffuse loss ot к Kb nesulLLng partly from atrophy and
pari Iу from r e l r a c l i o n i>v L h e fibrovastulaf Ж & и е !F I .
Сt: Ию(огп icrogra ph of hemonrhagi-r delathm ent of Lhe KF3t
and reLina in a palienl similar lo A. Blood in- the sub-KPt
sfHice has undergone urealer degradalion Lhan Lhal in Lhe
subretinal space.
H : E-’Fiolomicrograph o f a pi^menl-od vascularized subretinal
near pillow ing hemorrhagic delachmenL o f lhe Fil’E: and ret­
ina. NoLth degeneration of 1her outer relinal layers and degen­
eration and proliferation- of the overlying fifjrovascular
scar. Arrows indicate Bruch's ГгсетпЬгат^К
iC lr u n i С . и ы ^ : (.1 . L n t l H In y in C J.i m .''
slaining. In some cases, cystoid macular edema and degen­
eration may be present overlying flat, dlflicull-to-detecL.
involuted neovascular membranes lhat extend Into the
center of the fovea [see pp. 42-43).
I'oll owing develop menl of a large hemorrhagic detach -
menL of the KETL and retina, degradation of the blood
beneath the RPE usually causes a brown or yellowish
sub-ЙРЁ mass to form {E-igure 3.24E-). The blood In the
subretinal space surrounding the RPE detach menl often
requires a longer period of lime before a color change is
noled and before the blood is degraded [figure 3.27A).
Ihere is a gradual organization of the sub-RPli blood and
exudate by further ingrowlh of new vessels and fibro­
blasts from the choroid (Hgure 3.27C). HvenLually (he
exudative mass may be replaced by fibrous tissue contain­
ing varying degrees of hyperplaslic RPE [E'igure 3.27 Br Cf
and 11). 'lhe cicatricial lesions vary Ln color from while lo
brown or even to black and may be mistaken for choroidal
melanomas [figure 3.27B). Often anastomosis between
the relinal circulation and underlying choroidal circula­
tion develops within these old disciform scare {Eigure
3.27C}.-'0|‘' Ihere Is a general tendency for the devel­
opment of a similar pattern and size of disciform detach­
ment in lhe fellow E'luoresceln angiography in the
cicatricial stages of disciform deLacbment demonstrates a
wide variety of pictures, some of which may be similar to
dial produced by choroidal neoplasms.
M assive Exudative D etachm ent o f the Retina
(Sen ile Coats' Syn drom e}
In Jiiiob-t patients with drusen, lhe area of disci form delach-
menl is confined to the macular area and peripheral vision
is maintained. A few patientsr however, show progressive
exudative detachment of the relina lhat spreads far beyond
the macular region and may cause severe loss of periph­
eral as well as central vision (figure ^28D -J)VK':f,-36[-L:!l:1
Multifocal areas of eccentric choroidal neovasculariza­
tion and serous detachment of the UPE and relina may
occur-4"111'-' Extensive deposition of yellowish exudale
occurs in the subretinal space and in the outer layers
of the relina. It typically spreads initially in an inferior
direction, 'l'he fundus may resemble that usually seen in
younger patients with massive yellowish exudative detach­
ment of the relina secondary lo congenital Lelangieelasis
of the relinal vessels (the most common cause of Coals'
syndrome in young patients). The cause of this unusual
decree of exudaLion from the choroid in ihese elderly
patients is unknown, 'l'he exudale may eventually resolve
spontaneously, hut it Leaves in its wake marked widespread
degenerative changes in (he RPE and retina. Relinal neo­
vascularization and vitreous hemorrhage may arise as
complications of the chronic exudaLive detachment.
B u llou s Sero u s Retina! D etachm ent
IJarely these patients will develop massive bullous serous
delachmenl of the retina caused by chronic leakage of
serous exudate from large, highly vascularized ЙРЁ detach­
ments or disciform mounds that are usually located in or
near the macular area (figure 3.2ill?-JJ. Lon g-du ration.,
moderately intense, lai^e-size applications of laser photo­
coagulation to these fibrovascular RPE detachments, occa­
sionally pholodynamic therapy and anti-VbGP therapy
may cause reattachment of the relina and return of ambu­
latory vision [figure 3.2S).
Secondary H em orrhage from a D isciform Scar
A second ary exudative or hemorrhagic delachmenl of the
RPE can develop around the edge of an old disciform scar
and produce a lesion adjacenL lo the scar Lhat on occasion
'■f.Jf! Massive exudative retinal detachment
(Coals'syndrome) caused by age-related macular
degeneration.
A and B: Righl eye or" patient with large disciform delach-
mjsfcjFt and HubrtiCinal and ini rarct ina I ink I exudation. LhaL
extended to lhe ora s&Tgla inferiorlv.
( . : Hislthpalhoiogy of massive 11pdprtrteitf^Ccefius suhrtfLi na I
с \u(1.1!г )n c v i1riyi 11 .1 Inriii' macular .anti juxl a papillary cho­
roidal neovascular complex in an feltferffi paLient With
related mat. u]а г degeneration.
D —|: Massive exudative buEEnus r-c?Li nл I detachment caused
by j .large, orange, organized ostiamacular retinal p i u n i
-epithelium (.RPE) delachment (arrows, D-H|i in Lhe rigfiL
of a 74-year-old man wEwse lefl eye was blind from rubeo-
tic glaucom a caused by a s-imilar massive exudative retinal
deLnchmenl complicaliiT^ a^e-reiaLed macular degenera­
tion. Mote that the organized RPE detachment located Lem-
paral lo a white disciform scar showed minimal evidence
o! fluorescein slain ing (arruws, E-G). Argon ptioLocoagula-
Lion Was placed on lhe surface of Lhe organised RPE delach-
ment (arrows, 11 and was successful in causing resolution of
lEie Emllous relinal ddacbm ent and restoration of gmbulatcwy
vision 4 months nflej Irealmenl (J).
may cause (he physician to remove the eye because of a
suspected melanoma (Ligure 3.15¥ and J).2lja
Other Complications of Choroidal
Neovascularization
Vitreous Hem orrhage
L'he initial hemorrhage from CNVMs may dissecL ils way
into the retina where it is visible biomieroscopically as a
focal inlraretinal hemorrhage. The bleeding may be suf­
ficiently intense Lhal blood may break through the retina
into the vilreous and cause a massive vitreous hemor­
rhage {Figure Ш )1Ji'3™1 'ihis process of dissection of
blood Lbrough a defect in the relina is different from thal
of blood slain ing of the vitreous, which occurs more fre­
quently in these patients as a delayed phenomenon fol­
lowing lar^e hemorrhagic detachments of the RE5L and
retina (see previous discussion).
-
Ag&-Rdntejl.A&Kular 1.2 I
M a ssive Hem orrhagic D etachm ent o f th e RPE and
Retina
Rarely hemorrhage from a CNVM in the macular region
may produce a massive detachment of lhe RPL, relina, and
choroid, as Well az vitreous hemorrhage, closed-angle glau-
com.i and loss of lhe eye.ч'-' 'Ihis is more likely Lo occur
in patients receiving anticoagulant therapy or with a sys­
temic disease affecting the clotting mechanism (figure
3 .2 ^ 1 }™
Peripheral Exudative an d Hem orrhagic D isciform
D etachm ent
tlderly patients with macular drusen or without evidence
of AMD may develop serous and hemorrhagic detach -
ment of the retina second ary lo one or more siLes of sub-
KJM: neovascularization in lhe equatorial or pre-equaLorial
area, usually in the temporal half of the eye (I'igure .1.26}.
I.arge areas qI" serous or dark-colored hemorrhagic detach­
ment of Lhe RL’L in the periphery may be mistaken for a
choroidal melanoma because of the detachment's unusual
peripheral loca(ion.4IIJ 165 Many of these palients Will
show some evidence of peripheral sub-RPt neovascular­
ization in the temporal portion of the opposite eye. These
detachments will usually resolve spontaneously without
treatment. Jn those cases complicated either by bullous
exudative retinal detachment or by extension of yellow­
ish exudate derived from the neovascular network inlo
the m acuta, pholocoagulaLion or cryotherapy may he ben­
eficial {Figure 3.26 A-С). I^ripheral sub-RPE neovascular­
ization frequently develops as part of lhe normal aging
process in the peripheral fundus and is derived primar­
ily from Lhe ciliary body rather than the choroid (ligure
3.2G J . ^1 - ■ (See- discussion of peripheral idiopathic
choroidal neovascularization, p. 140.)
G eographic o r Central Areolar RPE A trophy
Although most patients wilh drusen lose useful central
vision because of complications of choroidal neovascu­
larization, approximately 5-Ю^Ъ lose central vision as
a resulL of lhe development of one or occasionally more
sharply circumscribed geographic areas of atrophy of the
RPE and relina in the posterior pole (i'igure 3.2У)/41'- 'i:
Dehydration and calcific crysta 11izalion
of druseii are often the forerunners of geographic atrophy
Эг29 Geographic atrophy in patients wilh macular
drusen,
A - t : Gradual unlargemen: of atoa of geographic atrophy
occurred in a b3-year-old mafl over a 6-yfepr period. Visual
acuiLy in A was 2(У&О and in С was 2CV20Q. NoLe changing
paLLem a t drusen, some1o f whn:h are calcified (jrtiflib).
D - F: 3n 1(J7 0 ihis ijl -ункг-'old wom an pr^senfed w ilh L>i!aL-
eral large diLisun and л siitous delacbment of the retinal pig­
ment epithelium ■К I^E i (^m W s, D ' in hoLh eyes.. Nole Ihe
stawoped bortJ-tir of I by KKL detachment resulting from con­
fluence Ы Urge drusen. Visual acuily w as 20/30 bilaterally,
l'he ri^ht eye was lrealed with laser apphcalions Lo the mar-
liir of lh-е КЗЧ: fh lat h merit. The hi PL delathm enl in the It'll
eye Spontaneously to J lapsed mid whs rej >1need by a pa Hern
□t" geographic .iLrophy lhal t ftahjjed VEry Гit1It? beLween I 974
It' and T "Hi. liI which lime LjctLb fundi looked him Liar and
Lhe Visual acuLLv was 20/50 bilateral ly.
G -J: Geographic alrophy o f the R PE in a 7T-year-oEd w om an
with large drusen. Sim ilar changes w ere present in the fellow
eye. Early angiogram showed evidence of partial preserva­
tion of the choriocapillans in Lhe area of geographic atro­
phy (И). Late angiogram showed staining oF Ihe choroid (If.
Several years JaLer m any of the drusen have faded Find Lhe
area of geographic atrophy has enlarged. Mote calcification
ot some of Ihe drusen (arnowt-j.
К and L: Geographic atrophy in a 6 5 -year-old man with dru­
sen. His visual acuity was Э/200 in the righ-l eye and 20/d0
in the left eye 4 months before be died. Histopalholojjic
examination revealed a sharp margin between lhe relattvely
normal retina and choroid and a zone of absence of Lhe
oliIcii" relinal layers and R ME I.:. TItuto was partia1 closure of
the choriacapiEEaris in Ibe region of the geographic atrophy.
that may begin either centrally or paracentral ly. Loss of
central vision occurs slowly and progressively as the area
of atrophy concentrically enlarges. A similar pal Lem of
atrophy is often seen in the second eye. Approximately
20% of these patienls, however who deveEop geographic
atrophy in one eye vrtJl develop choroidal neovascu­
larization and its com plications in the second eye.-11'0
J:iuorescein angiography shows varying degrees of loss of
the choriocapilEaris within the area of geographic atro­
phy (figure 3.2УС and li). Histologically the area of geo­
graphic atrophy is associated with focal Loss of (he relinal
receptor cells and RE^Ei and varying degrees of atrophy of
the choriocapillaris [E'igure 3.29К and L}.
 The pathogenesis of these sharply circumscribed areas
of atrophy is not understood. It is not known ivhether the
partial obstruction Lind, atrophy of the choriocapil laris are
the primary cause of. or the result of, the overlyLng RPli
and retinal atrophy. Geographic atrophy of the КРБ, retina,
and choriocapi Ilaris i s an ophthalmoscopic finding lhat
occur? in association with many other diseases. Including
Sorsbys central areolar choroidal sclerosis, basal laminar
drusen., Stargardt's disease. Best's viteliiform macular dys­
trophy. cone dystrophies, rod-cone dystrophies, chioro-
qulne retinopathy, ICZSC^ and traumatic macu lopalhy. In
palients with AMD, geographic atrophy may develop in aL
[east the following three ways: (1) with no precursor legion
other than macular dmsen; (2) following an acute tear Ln
Lhe КЕЧ-: (see pp. IQtf-Ml); and [3] following collapse of a
long-standing serous КРГ delachment.
Prog no il li
Most palienls with macular drusen never experience sig­
nificant loss of cenlral vision. The average age when they
develop loss of cenlral vision in Lhe first eye Is approxi­
mately 65 yeaii-115-154-3^ 3®^ Ihese patients will lose cenlral
vision in lhe second eye at a rate of approximately 5-10%
each year thereafter. Ihus many patients who have visual
loss Ln one eye will never experience visual loss in the sec­
ond eye. Nevertheless, AMD is the leading cause of legal
blindness not amenable to surgery Ln lhe USA and the UK.
Etiology and Pathogenesis
Our lack of knowledge concerning lhe cause of AMD and
macular degeneration parallels our Inability to alter Its
natural course, lhe only established factors of importance
regarding causation of Lhls disease relate lo age, race, and
heredity.Lfl5,211,343 The breakthrough in relating genetics
to AMD occurred in 2005 with the discovery of comple­
ment factor H (CJFHJ variant In 43-50% of patients with
AMD by three groups. i?0_i72 Since then, other genetic risk
factors, including ARMS 2 [H T JM J), complement factor В
(C2), and C3 have been found to be variously associated
with the risk of A M D .1' ,' 1'" РЛ ф п $ and ABCA4 render
a risk in less lb an 5% of AMD patlenti3® " ^ The С Ж
variant has been studied extensively in various population
groups and seems to be most commonly associated wilh
AMD. However, preliminary da La suggest that AtfMS.2 may
be more specific Ln rendering severity to the condition,
^omplemetit activation occurs as a result of inflammation
and healing which may be Lhe ULtderlying mechanism
con iri bu Ling to the со nsti lue n ts о f d rusen
3.30 Treatment of exudative age-related macular
degeneration,
A—G : T liis 67-year-old man presented w ilh a serous pigjnent
epithelial delachm enl and л notch w ilh a visual decline lo
2 ()o 0 Lhal could be cor retted Lo 2(1/25 w ilh a hyperopic
shifl. An^iojjmm cp rfjim ed Lhe serous detar hmSMt w ilh л
hoi *pol at ils superior ed^e ill and C.. O p lical coherence
tomography revealed nubnetmai Fibrosis (SKI-i adjacent to Lhe
relinal piijmunl epithelium detach muni 11». H e subsequently
unduiwenl 26 Ljcen tis injections in ihis eye over 3 yfciars.
After injection 15 he developed S la p h y fo c a c c u s epiderm i­
s's endophlhalm ilis and received intravilreal antibiotics Hind
dexamethasone. Persisting inrlammaEion led lo a pars, plana
viLntit. Lomy and lensectomy J days taler. I п Irav il rea I Lucenlis
was continued for further 11 injections and a total o i 26 for
mild persisLenL SE F (E). Two and three years later his vision
is slill w ilh a persisting L3t D And no SKF (F and (Li..
NoLe lhe ^ood retinal thickness, w hich accounls for Lhe
2СУ25 vision. In The m eanwhile the left eye also developed
a com bined serous/lfibrovascular pigmenL upiLhelial detach­
ment iind received 1I Lucent is injections. Vision remains al
20/20 in Ihe left wiLh a hyfioropic sliifl in spile of an ек1тлfo­
vea I relinal pigmenL epithelium rip.
H-L: O n e w eek post pars plana vilreclom y and fjas displate-
menl o f subrelinal blood in ihis Й2-year-old wom an ruveals
an occull membrane iVHh late punclale staining it and i .
Note lhe i learin^ of blood in Lhe cenLer ( № She was con­
tinued on anli-vascular endoLheffal growth Factor injections.,
and developed a new larger suhiolinal hemuioma afLer Lwo
further injecLions <K|. Л repeal vilrecLomy with Lissut plas­
minogen activator tLpa) injection displaced lhe blood tempo­
rally and interiorly 'ILj. ih e maintained moderale vision for
a few rodhtfrs but eventually developed д disciform scar in
spile of continued Lreatmunl.
Other environmental and health factors and biochemi­
cal aUerations of possible importance as either causative
of aggravating factors include: exposure to su n Bg b t^ -336
cigarette s m o k in g ,"iM fentale hormone replacement
therapy.wo systemic hypertension,.^1 anticoagulation;11- |,jl
dennal elastosls of exposed shin surfaces.1 loiv levels of
serum c a r o t e n o i d s , elevated semm cbо(ез1его]3;ir-iS4i
and serum zinc and copper. '''v' low levels of semm sele­
nium’01' and serum eeruJoplasni/4''-"1, high hematocrit,11'^
high while cell blood j^ w it406 h ^ e ro p la ,in c re a s e d
scleral rigidity, auto antibodies lo retina and retinal astro­
cytes, 111 decreased levels of catalase activity Ln the ftPE.344
decreased Ee^'els of hpluronic acid Ln the choriorellnaE com­
plex,"1^ and use of anllcoagulanls.ICK! Much is being dis­
covered and a lot remains lo be understood regarding the
pathogenesis of AMD In relation to genetic and environment
risk factorsr and is outside the scope of this clinical text.
Reticular Pseudodrusen
Reticular pseudodnisen (KIMJ) [figure 3.3i] is л yellowish
interlacing pallern seen best in red-free or blue Li^ht, most
often seeii straddling the suptrolemporal arcades* but can
be present through out the macula, across the infero-tem-
poral arcade and nasal to the oplic disc:
liarly Йп. it is made up of several punctate yellow dots.. lhal
evolve inlo an interlacing pattern. Lt in not usually visible
on fluorescein angiography, and correlation wilh aulo-
Eluorescence and spectral domain ОСЛ' shows the depos­
its to Eie between the retinal pigment epithelium and the
photoreceptors [figure ]:ven though
pseudodmsen is seen most often in patients with ARMJD^
it can sometimes be seen in eyes with no other abnormal­
ity. Though several papers describe it Lt) be a feature of
advanced AMD, mostly neovascular, this author has seen
pseudodmsen lo be distributed over all grades of A_fi_MD
(figure 3,311-1 to К), and even in eyes without ARMD. '['he
incidence of RE4> is underestimated as it can often be over­
looked especially in eyes with some degree of cataract or
subretinal flu Ed, and also early in its evolution before it
has developed the interlacing pattern. At the present lime.,
the complete significance of RPD in relation to severity of,
and association with genetic markers of ARMD is not fully
understood.
Fig u re 1.31 R e tic u la r p seu d o d ruse n .
U n ila te ra l p s e u d o d ru s e n .
A and B: S2-year-old tjjale w ith moslly in Immediate dru-
sen in the fovea (grade 2 age-related macular degeneration
i'AM Dll and pseudodruscin in the superior half of lhe macula
iA . The left eye had occult choroidal neotaht uiar memt>rane
(C N V M ) '.grade 5 1w ilh no BMSudddruS^n (Bj.
B ila te ra l s y m m e tric p s e u d o d ru s e n w ith a d v a n c e d
AMD.
C-£: This 77-year-old wom an had a vision of 2Q/70 in Ihe
righl and 20/5D in Lire left eve. Exlensive pseudodrusen
were seer* sym m etrically distributed in lh e Lwu eyes; :CJ and
D . The rijjhl Eye had a disciform ьс:аг and the fefj an uccull
C N V M . lhe red-frife image of lhe lelL eye demonstrates Ihe
pseudwdrusen w e ll (E l
F and G : This 90-year-old wom an has bilateral active cho­
roidal fiedvast uiari^al ion, lhe left gvl1 durminslraLin^ o c l l i I i
chririoretpal anastomosis i|inLrarelinal hemorrhage, Cl. The
fiseududrUsen in tfiSiri^Lited in lhe superiiip m acula si raddling
the superoLemporal arcade and es tends nasal lo the dine in
holh ryes i.arrows;-.
H and I: Bilateral pseudodrusen w ilh mild A M D Igradt? ] al.
E3oth feyes show pseudodrusen Lhat is symmetrically distrib­
uted superior Lo the disc with very few small pu m late drust'n
in each eye.
1 and K: Pseudodmsen visible on color phoLos and red-free
images, w ilh inlermodiaLe drusen vi-sible only on Ihe color
phoLos.
L: Pseudodrusen l o c a l s to lhe photoreceptoi Laver on opli-
cal coherence tomography seen just anterior to Lbe retinal
pigment epilhelium ’'^rrowt'i.
I A . i n f i! i L i j ij r i . u i y u l D r . J- r . in i'u B e t i h i . i ; C —£ ■: f t j f t e i y n 1 I Jr . K i u l
йетЬрьд,]
Occult Chorioretinal Anastomosis
lhe presence of small irilTfrrrtinal hemorrhages in eyes
with drusen and other features df agerelated macular
degeneration as a sign of occult, chorioretinal апаз4нщо-
sis was brought lo attention by work of Soubrane and
Closeas.-w Debate has ensued about the site of origin and
evolution of the chorioretinal anaslamosis since Vannuizi
coined the term retina] angiomatous proliferation
(RAP). lie describes the vascular malformation to arise
in the inner relina and grow vertically downwards towards
the КГЕ: and eventually reach the space between the RPli
and Bruch's membrane where it spreads horizontally. At
this stage, pigment epithelial deLacbment may be seen.
Others believe that a loss in Lhe photoreceptors from AMD
brings the inner retinal vesseEs in closer proximity to dis­
eased IJni/cboriocapillaris complex thal induces growth
of bridging vessels to communicate With occult choroi­
dal neovascular vessels possibly already present In that
Location.41-1 At our present understanding, it is likely both
mechanisms play a role in different eyes, sulfite lo say I hat
management of these eyes is difficult; laser photocoagula-
tioiir l3D I' and anti V E G F agents have all been used. Et is
Likely that the best results are obtained if we recognise its
presence early in the course and use anti V\iCY agents (see
case illustrated in I'igure 3 . 3 2 ) . ofl en the occult
anastamosis is bilateral and looking for the small focal ret­
inal hemorrhages in the fellow eye Is vital.'11"
3.32 OccuEl choгм)retinal a nastomosis (O t ЙД).
A.—j : This flO-year-old wonujn was fibal№ !ei| for melrimor-
phopstflj and decrease :n hei ri цhI eye vision lo 2(1/200. !ihe
was. found to have exudative age-reEated m acular degen­
eration w ilh an occult choroidal neovascular membran^ in
her rij*h1 eve. The vision in the left eye was 20/20 and care­
ful cjxjimin^tion fevealcd Lwo (onfl smaller lhan the oLherJ
inlTa retina I dcrf hemorrhages temporal lo Iht! foveal cenler
that isitej also seen on Ihe red-free image iA and H, arrows!.
Opffeal coherence tomography (O C T J through Lhe red hem­
orrhage revealed an intrartfartijl channel es.lfndinj' towaips
Lhe retina] pigmertf epithelium (C). Due Lo shadfjwing the
i : ■"i:.. i: ii i'i-.1
, ( ourso )l lhe <li^nncl is ncl \ !^i!:■
! . She was
advised inlravitneal bevacizum ab, bul did nol receive it by
the referring retina specialist. Three months Ia Let (he hemor­
rhage appears more prominent and hei vision is slill stable
a I 20/20 lD r arrow.. tX JT reveals lhe com m unicating ves­
sel. ih e was Parted cm monlhly injections of bevacku.mab,
and Ih e red lesion became very smaFI; the second one disap­
peared -I months later (F). Sis 'iCl and IS months laler 1Hi-
on Iv lhe SJupediCEa] intrarelinal com ponent remains on OCT.
Two further years later she is slifl stabEe w ith vision of 20/25—
from a catafact ll'i. A month afler ihis picture was taken she
developed a d iv e leakage and repeived inlravilneal bevacl-
ium aft, the membrane and vision stabilised after six injec­
tions and her vision remains al 2CV.iO-.
Ag^-Related.Л1лта1пг Dt'ficm'Tfiiuw \2
Treatment
Many authors have reported lhe possible benefit of
^holccodplatbn in treating the neovascular cci]nplica­
tions Of AMD. L^l3a.]i3.175r.il01J4fiJ84J3i9133*r3ilrJ5i(,J&5,.l]*-L}!*
Randomized controlled cl in Lea] trials have convincingly
dema^slrated lhal argon blue-green laser and krypton red
Laser treatment is of value Ln Lhe treatment of wet!-defined
CNVMs in lhe parafoveal {outside the capillary-free zone),
juittafoveal (inside but not beneath the center of the capil-
Eary-free ione), and subfovea] membranes in pat Lents with
AMDJ:M5'21>r^ s!!^J4-WLj^ JS 'these studies have a]so demon­
strated the vaiue of laser photocoagulation Ln the treatment
of persistent and recurrent C N V M ."'J;>I 1,1 Unfortunately
the great majority of patients with AMD present because
of Iон of vision caused by ill-defined or extensive sub reti­
na! neovascular lesions where there Hire no guidelines for
Lrealment.J J in 20 00, photodynamic therapy was intro­
duced to treat classic subfovea] CNVM. Approximately 54^-b
showed stabilization and less than 15 letters of visual Lots
(severe visual lossj; however this treatment did not restore
or improve vision in more than 7-9% of patients.
Since the Introduction of intravitreal ranibizumab..
a E-'c component of ^nti-VEGF antibody, visual recovery
and stabilization haw been seen in up lo 33% of paLients
wilh neovascular AMD at the end of 2 years. M ARINA and
ANCHO R trials established the success of this treatment
in both classic and occuEl Since then beva-
cizumab, which is the complete antibody to VHCIi has
shown equal success Lit Improving and maintaining vision
tn neovascular AMD patiiqflis.t:W' Wi Lise of ranbizumab and
bevacuumab has become the standard of care for neovas­
cular AMD at the present time. Some people use a combi­
nation of anli-VfcCF injections with pbolodynamic therapy
to reduce the frequency of Lntravitrea! injections. lbe injec­
tions are being done at various intervals based on experi­
ence and resulLs of several studies. Generally at Least four
monthly injections are given initially, and further injection
intervals are based on individual physician preferences.
'ihere is little evidence to support laser treatment to
reduce or eradicate drusen, and there are no clinical trials
regard ing the effectiveness of such treat ment
Surgical Treatment for C om plications o f AM D
I’ar; plana vitrectomy has proved useful in removal of vit­
reous blood that fails to reabsorb spontaneously (figure
З.ЗОН-Ц:4*4 it also appears to haw some usefulness tn the
evacuation of large subretinal hematomas in the macular
area* particularly when used in association with tissue plas­
minogen activator.IC"' Surgical excision of CNVMs, which
Lie in [he sub-RPK space in patients with AMD, appears lo
offer no advantages over laser photocoagulation in regard lo
restoration or preservation of visual fimction,2H1,,2ei^w,-J7fi
lioth result in permanent lass of retinal function in the
area of the neovascular membrane. (See discussion of sur­
gical excision of lypes L and 11 choroidal neovascularization
in Chapter 2.] Jhere is hope that transplantation of ЙРВ
after surgical excision of subfuveal membranes, or other
ЗгЗЗ Basal laminar drusen.
A and В: A 23-year-old wom an w ith 20/10 visual Sell tty.
Early arteriovenous phase anjjio^rarn (Bl reveals mu Hi pie
punctate drusen not eVldeint in A.
C—L: A 70-year-old л ю т л п seen Ijetnuse o f inoLa morphop-
sia in boLh eyes. Visual acuity in the rLghL eye was 20/40
=1п-rJ in- lhe 3efl eye was 20/40. A rraw s ^ dic;H e localized reLf-
nal detachmient and yello w subretinal exudate (CI.I. Sim ilar
findings were present in Lhe lefL eye. AngjograpEiy th aw ed
prompL hyjjerl luoresconce Ы innumerable uniformly small
basal I ami n j г drusen a tip laLe slam ing of larger variabiy
sized Lypical drusen as well as Lhe subretinal exudate in Lhe
right eye (D-F(. Angiograms o i left eye showed early local
slainin^ arrows, ti nn-ci lale s-Lliii T i сё" subretirtal exudate
(C and Hj. Thirty-six mtkiths laLej, sporttari^cAjs nesoluLio.n of
lhe subroLinal fluid i-п the iiцhI. eye had occurred (Ij. Visual
ncuily was 2CKG0.
|—L: A 5fl-year-old w om an with a J-year history of decreased
vidian caused by similar viLelljlorm retinal drfathm enL in
bolh eyes (Jf. Nole fluid level o i yellowish subreLinal exu-
diiLe. Visual acuily was 20/200. EEeclro-uculo$=iaphy was nor­
mal. Angiography showed basal Laminar drusen and si a in ing
of lhe suhfeLinal exudale К and Ll.
ll- г и т O.i^ss cl J it * '■ J3LihliahL4J w i!h р и г т 1ыыг>п :ш г п Г1тс A m L 'r i o . i n
Jo u rn al o f Uphflti^jlntulugy; Dopyrij^il h y Ih e O p h l l ’u im ic: Puhilhhin^ Cju.l
modifications of the surgical technique, will ijnprove Lhe
visual results.'1'''"1,-■A' ' SutgLcaE relocation of the macular ret­
ina has been suggested as another possible method of restor­
ing central vision in patients with AMD.'|,M
'L'he tiigh susceptibility of lhe retina to oxidalLve sLress
tweause of the cLose proximity of hLgti concentrations of
polyunsaturated fatty acids in the pholoreceplor outer-seg-
ment membrane. where exposure to short-wavelength light
may generate free radicals has suggested the possible value
of aLitioxidants in retarding the development of AM D .: ' jSD
'Ihere is evidence lhat increased serum levels of alpba-
locopheroL and an anliojudanl index, including ascorbic
acid, alpha-tocopherot, and bela-carotene, are protective for
AMD, ihere is. however, no evidence lo show that daily sup­
plementation of vitamins or niinerals is of any value in pre­
venting or ameliorating A M D r ^ 60^ 4 I he Age-Related Eye
Disease Study found retardation of progression of nonexu­
dative AMD in approximately 29 % of patients treated with
antioxidanl viatamiiiSv zinc, and copper. Several pilot studies
have suggested lhat low-dose externa I-beam irradiation LreaL-
ment may be of value in the treatment of subfoveal neovas-
cularizaLion.'11,'"|,с' Kecognilio]i of the easiest syjnptoms of
macular detachment by the paLienl aatd pntimpt exam illa­
tion (within several days after onsetJ by the ophthalmolo­
gist are the t>est means of preventing loss of vision in this
disease. ]Clients should tre instructed in regard to the use of
the Amsler grid and near-vision chart and Lhe importance of
prompl e x a m in a tio n .1Sfl 'l'he role of trauma, intraocular
surgery, and anticoagulants in precipitating exudation and
hemorrhage in these patients is uncertain:4®9,
Mosl patients who have lost central vision in both eyes
will benefit from the use of any one or several of the wide
variety о t' low visual aids available.''" ' :|
BA SA L L A M IN A R D R U S E N A N D
M A C U L A R D E G E N E R A T IO N
'Jlitre ii accumulating evidence to support lhe concept of
nodular thickening of the basement membrane al" the R]>H
as lhe cause for a distinctly different pattern of uniformly
small round drusen that may appear in early adulthood
and Lhat occur With equal frequency in blacks, Ljitins.. and
whiter {Figures 3.33, 3.34A-t, and 3,3 SA - ]^ - 3-437 Ihese
peculiar basal laminar or cuticular drusen predispose
patients, particularly white persons, to the develop menl
Ln the siitth decade and beyond of typical or exudative,
larger and variably sized drusen and occasional loss of
central vision lhal is often caused by an unusual vitelli-
form exudative macular detachment (Kigures З.ЭЗ, 3.3 4A,
and 3.3Si ).'1"'’ frasal laminar dmsen are usually 25-751im
Щ size and are discretely round, slightly raised, yellow,
subretinal nodules thal initially may be randomly scat­
tered ill the macular area of young adults, but later often
become more numerous and in some patients are grouped
in clusters of 15-20 drusen. These clusters, in turn, may be
closely arranged in a lightly knit pattern giving the entire
macular and paramacular area an orange-peel appearance
biomicroscopically. 'ibis patter]! is coarser and is com­
posed of more discrete flecks than thal seen in pseudox­
anthoma elasticum [PXEi]. Hasal laminar drusen are more
easily seen in young patients with bninelte fundi, '['hey are
more easily visualized angiographically than biomicro-
scopically. I hey fluoresce discretely during the early arte­
riovenous phase and in many patients give the fundus a
4tars-in-lhe-sky" or "mi Iky-wayu picture (Figure 3.33 b,
D, E, and С;).: '^ " : '1Ье fluorescence in basal laminar dru­
sen fades from view earlier and shows less in tense stain­
ing than in the case of exudative drusen (Kigure 3.33D-E').
On autofluoiescence imaging, these punctate drusen show
a hypoautofluorescent center surrounded by a ring of
increased auto fluorescence [Figure 3.3 5A-]).
Patients, particularly while persons beyond age 50 years,
wilh basal laminar drusen may begin to develop super­
imposed, variably sized exudative drusen usually in the
central macular region. They may experience visual loss
usually caused by yellow serous exudative detachment of
3.J4 Basal laminar drusen.
Д -C: Vi tel Ii form m acular deLachmenL in this 54-year-old
wom an with a 2-yenг histoTy Ы clifffc:ulLv w ilh adaplion lo
changing li^hLin^ conditions. Hi*f visual acuity was 20/JO
bilaterally. Both eyes had similar vitelliform m acular lesions
and angiographic evidence of bntal lam inar drusen.
D: Diaj^am shewing structure Ы: 1r tvpicai or exudative drusen
wilh detachment of lhe retinal pi^pnenl epitheljum iHPEii and
nurmaJ-lfiicknesE- basemen: m em brane'bm I from inner collag­
enous part ol Bruch's membrane IBM ) by extracellular material:
2, Ejasal laminar drusen composed or modular thtefcening of the
bascmenl membrane of the Kl'b: 3, ccHitbmed basal laminar
and lypil:.iI or "x.i:i.4iv;-d:4.-;-^ i ' . (boricк .ip ari*;.
E: Electron micrograph of com bined basal laminar and exu­
dative drusen. lh e I w o adjaconL а пеан of nodular thickening
ot th(' К ГЕ basement membrane (bm, sm all arrows) and i t
normal-thick ness basement membrane i.lar^e arm w tl are
detached from Ihe co33a^enous and elastic part of Bru ch s
membrane by amorphous material 4am^.
Cultcular and calcified drusen in patients with lype II
membranoproltfefalive glomerulonephritis (MPGh
F-l: A 50-year-old man, who had a history ol" renal trans­
plant al ауеь 16 and 35 years because of typo II MI-’C,
complained of Eilurred vision ol 2 m onths dura Iion. Visual
acuily in riLilil eye3 was 20л200г left eye 2(5/20. NoLe variabil­
ity of the size o f the drusen, some of w hich appear calcified.
AngiogTaplTV revealed cuLiculai drusen fiH and 31.
1 and К: А I ^-year-old nnan with childtiood-onsol diabetes
and nephrotic -syndrome associated with type II M P G . Visual
acuity in Ihe right eye was 20/20 and of the left eye was
20/25. NoLe cluslers ot" liny basai laminar drusen (arrows/
and mild background diabetic retinopathy.
L: Histology of an eye with basal laminar deposits shows the
local ion at lhe base of the Kt’t iarraw).
(О jr id E Г п з г п Lj.hSb- c l ,i- '." ' ' I'u U jih h f . '[ l W i t h р и гм и-^ю п Ггсчи l l i u
A m e j i t a f i Il 11j -гi i : 11 4. i Г i! j |□h ! 11.11j t i с :■I u ^ V : l r i^ lil I vy l h u (. J |.ih Ih i.il in il
lJu M ; - h i n ^ q f t j ) L c iH jrlL i y ii f k j l | j h i k . i l 1. i . ■
(be retina in one or both eyes [Figures 3.33C and J, 3.34A.
and 3.35F]j When discretely outlined and densely yellow,
diese detachmenLs may simulate the lesions seen in best's
vitelliform dystrophy and some patients with adult vilel-
liform foveomacular or paltern dyslrophy (E'igurcs 3.33]
and 3.34AJ. They may be mistaken for serous detach­
ments of the KPL. In the early phases of angiography this
yelEowish subreLinal fluid obstructs the background cho­
roidal fluorescence. Later, multiple progressively enlarging
siles of movement of dye through lhe RPH into the sub-
relina] fluid occur (E'igures 3.331-.-К and 3.34J! anil C).
]his pattern may be Jin istaken ly interpreted as choroidal
neovascuLarList Lon.
The older patients who develop yellowish delachment
3. Cuticular drusen and aulofluorescence.
A—E: WuN-domarc-iHod edges of Ihe cyticular dTusen ъичлп in
Lhe fovea and nasal I d чЕ>е disc in 1hiь 4ti-year-old Wui'rtan
w ilh a vision of 20/20 in each eye. The com pact druien
appeal as rings Vi-ilh я dark сел I lit and а EWperautofluores-
cenl o u I lt ring in Ejolh eyes ‘ Li and Cl. HigEi-poweT v ie w
shows Lhe lings more yiytdly (D and Ё).

of the macula often maintain acuity of 20/30-20/30 for F—J: This 45-year-old man had extensive cuticular drusen
in bolh eyes and a vilellifurm deladnmenl in the fovea. He
many monLhs with no change in the appearance of lhe
had Ereen trealed w i)b pholodynamit: therapy in Ihis eye fur
subrelinal fluid. In some patienlsr the subretlnal fluid dls- a diagnosis erf choroidal neovascularizaJion. He was placed
appeaif spontaneously and good acuily is restored (ligure under observatiail and 4he vision dropped Lo 20/400 from
3.331). '['he drusen in the area of Lhe detachment often the initial 2CV1 00 over -4 years; m eanwhile [he yellow mate­
disappear or become less prominent after reattach menl of rial was teahstifbed leaving й central geographic atrophy tC-V
the retida. In a significant number of patients geographic АкПпЙииГЙСепЁе imaging shows innumerable KypdSLrt-u-
atrophy of the К I1К and poor Visual acuity develop after lluorescenl dols surrounded by ЕтуреглиюГСиогонслт! rin^s.
aipept in lhe region of Lhe geographic atfdplty ;Hj. V itd<]n in
resolution of the detachment (I'igure 3.35h-H). Choroidal
the lell eye decreased lo 20^100 with patcEiy loss of relinal
neovascularization and serous and hemorrhagic disci­ pigment epiLhelium in lEie fovea and a sim ilar appearance of
form delachmenl may develop in some patients, 'this lat­ lhe drusen on lhe color photos a.nd aulofluorescenL images.
ter complicatioLi may occasionally occur in middle-aged К jmd L: This й4-уеаг-«Ы Wom an has e\udaLive druuen some
patients who have not developed superimposed exuda- Lit w hjcb are very large \Kl. 1bn- auKjfluonescenLe images
Live drusen. lhe electro-oculogram and eleclroretinogram appear simrLar to the culicular drusen, suggesting the ''ring
are normal. Most of the patients' siblings and offspring appearance" is likely tipi a led to lhe compaclness of Lhe dru­
sen and il-s distinct edge raLher lhan being typical o f cuLicu-
examined to date have shown no signs of the disease. 3L
Lar drusen alone (Ll. NoLe that the large drusen also have Lhe
has, however, occurred in other family members in a few
ling appearance (arrow).
cases.'4, Et probably will prow to be an inherited dystro­
phy primarily causing progressive thickening and nodu­
larity of lhe RVt basement mem brand similar to changes elastic zone. They proposed that all drusen represented
occurring in the comeal endothelial basement membrane focal thickening of the culicular or Inner part of liruch's
in t-'uchs' dystrophy (E'igure 3.34EU). Ihese nodules prob­ membrane secreted by tEie К L3b£ rather lhan Lhe outer elas­
ably begin to develop early in life. tic zone. Et was not unlit the advent of electron micros­
In addition lo the frequency of development of yellow­ copy lhal it was realized that typical or exudative drusen
ish subrelinal exudaLe., other differences between these were deposits of extracellular material lying between the
patients wilh basal laminar drusen and those with AMD relatively normal basement membrane (basal lamina) of
include lhe following: (1) visuaE symptoms occur less fre­ lhe RPE and the inner collagenous pan of Kruch's mem­
quently and they are delected on average 5—10 years ear­ brane, ]МД27'213<,Э^НИ It is likely that some of lhe uni­
lier; (2) the rale of visual loss after onsel of symptoms is formly small punctate yellow nodules lhal are seen in
slower; (3) spontaneous improvement in acuity is more small numbers in the macular area of many patients of
likely lo occur; (4) the incidence of development of geo­ all ages are basal laminar drusen and that some of these
graphic atrophy is higher; (5) the incidence of choroidal patients go on lo develop exudative drusen and visual Eoss
neovascularization and large exudative detachments ofthe later in life ( E'igure З.З.1)К and l.J. ll is nol possible biomi-
RPH probably is lower; and (6) the prognosis for retention croscopically lo differentiate one or several basal lamitia
of useful central vision Es better. drusen from smaEl lypicaE hard drusen or from focat Eipidi-
Clinicopalhologic study of basal laminar drusen by za Lion of K Pt cells.
Eight and electron microscopy has revealed thal basal Recent genetic studies in patients wilh basal laminar
Eaminar drusen are caused by nodularity of a diffusely drusen have found heterozygous 'iyr4Q2His AM D risk vari­
thickened ЙРЕ basement membrane (I'igure 3.34EJ.'1 " ant of C Ftt gene in five families of 30 probands.'01 'Ihe
J hough this is disli nelly different in appearance on light association of the same varianl in membranoprotiferalive
microscopy from lypicaE or exudative drusen that are focal glomerulonephritis lype 2, which also has drusen as a fea-
detachments of the RPL and its relatively normal thick­ Eure (Figure 3.34 E-' to К), suggests that the СI'H variant may
ness basemcLit membrane by amorphous and granular confer a common risk for drusen formation, and lhal other
material, cytoplasmic processes, and bent fibers-1 ■--*-1 genelic or environmental risk factors determine the occur­
immunohistochemlstry by Russell and coworkers has rence of exudative drusen, versus drusen of men]branopro-
shown thal the constituents of culicular drusen resemble llferative glomerulonephritis type 2 or cuticular drusen.^
[hose of exudative drusen.210 It is of historical interest lhat Dominantly inherited disorders associated ivilh culicu-
as early as 1836 Muller1147 and later Coats1"14 acid other !ar drusen North Carolina Macular dystrophy and Mai atria
Eight micmscopisis recognised thal liruch's membrane levantlnese and Sorsby's fundus dystrophy are discussed in
was composed of an inner cuticular zone and an outer chapter 3.
ID IO P A T H IC C H O R O ID A L
N E O V A S C U LARI ZATI O N
Patitbits may develop loss of central vision secondary lo
serous and hemorrhagic detachment of the macula caused
hy choroidal neovascularizatLon arising in the macula
(E'igure 3.36A-CJ, al the margins of the optic disc [E'lgures
3 36D-E 3.37, anti 3.33), and less frequently in the para­
macular { figure 3.36C-KJ or peripheral fundus [Figures
3.37 and 3.38) without any other evidence of intraocular
disease.503"*1-
Macular Type
When Lhe choroidal neovascularization develops in the
macular region of a child or a young or middle-aged adult,
El often occurs in association with a pigment ring or gray
mound similar to thal described in PO HS (type II subreti­
nal neovascularization) [E'igure З.ЗСА-С]. Class noted no
sex predilection Гог idiopathic membranes in the macu­
lar region Although Lhe cause of these neovascular mem­
branes is unknown, il is probable thal many of those
located in lhe macula In younger individuals seen in lhe
eastern half of the USA represent a forme fruste of POI IS,
whereas those occurring in patienls 30 years of age or
older are more Likely to represent a forme fruste of senile
macu Iar degene ra Lion.1,11
UltraslrucLurat features of three excised submaculaг
idiopathic neovascular membranes were similar Lo lhat
in patients with PO KS .^11 Spilznasand Boker studied 151
eyes wilh idiopathic choroidal neovascularizalion,- exclud­
ing all eyes With grealer lhan 6 D of myopia. They found
Lhat the probability of develop]tig neovascularization was
proportional Lo the degree of myopia." 1
3.3b IdtopaIh ic subreliна I neovascu!arizalio r.
A-С: This healLhy 45-vear-old wom an developed blurred
vision in her ":цЫ eye caused by л 5yp«? II subreLLnal cho­
roidal rtbovascular membrane of unknown cause (Af.
1here w ere no peripheral scare and lhe left eys was- nor­
mal. Anolljgrapliy revealed a J.ii-disc diameter membrane
ia nows. A and ti' thaL pixnjfebEy extended into the cenler ol
the fovea. The patient was scheduled for surgical E lu s io n
ut the membrane I jliI decided Lo postpone I be- Operation.
W h en she returned 6 months laLer, lh e viy:on- had returned
Lo 20/30, the subretinal blood and exudate had disappeared,
anti neova scula г membrane bad con I racled lo a smiill area
oulside the capillary-lree Zone (a rm w ^ Й .
D-F: B,i aleral idiopathic juxtapapillary subrelinal neovascu­
larization Narrows) in a frfr-year-old white woman. In her I ell
eye there was evidence ol" a small |.ixlapapillary neovascular
membrane and minim al evidence nf (JiaCLtlar degeneration.
The exudative delachmenl resolved sp&fflaneousJy. ie v e n
years laler she had developed a tew drusen in the macula
bilaterally, and visual acuity was 2 0 3 0 I.EJ. Twelve years aller
her initial exam i nation she developed a lar^e recurrenl nuw-
vessel membrane larrowt, K.l
G —Ki A large elevated subretinal pifjmenL epilhelium-neo-
vascular complex (arrows, G and S-lj ot unknown cau^e
centered in lhe exlramac Ltlar area temporally was associ­
ated w ilh exudative relinal delachm enl and los*. of cenlral
vision in this 76-year-old wom an. A lar^je scar bad been
seen :n lhat area ti yea re pT<=viouslv- Her left eve was normal.
A n g io ^ ap h y showed evidence ot widespread ill-defined
subretinal neovascularination |l). Ailer intense pholocoajjula-
tion treatment (II the exudative detachment resolved and 4
years later her visual acuity was 2iV40 ;K .
Juxtapapillary Type
Although idiopathic juxtap^ip LlLary- choroidal neovascu-
Earization may occur at я]! age-ь., El is seen most frequently
Ln women in the sixth and seventh decides of life (figure
З^йН-Е1').1'''- In Caucasians it usually occurs as a sin­
gle partly oig^niied juxlapapillary neovascular network
extending outward from lhe oplic disc toward lhe macu-
Ear area. It is- often surrounded on Lis temporaE aspect by
serous or yellowish subretinal exudate with or without
subretinal blood. In lbe opposite eye there is frequently
biomicroscopic as well as angiographic evidence of small
choroidaE neovascular tufls at lhe margin of lhe optic disc,
ihe visual prognosis for these latter patients is relatively
good, since the process often spontaneously subsides.
Nevertheless, they should be watched carefully and Lf they
show progression of the neovascular membrane beyond
the halfway point to the center of the fovea, they should
he considered for laser therapy. Sub-RPI; neovasculariza­
tion in the absence of hemorrhage or exudation is found
frequently in the pathology laboratory as an incidental
finding in the juxlapapillary and peripheral areas tempo­
rarily tn lhe eyes of elderly patients [Figures 3.1 SD and
З.Дб).-351'-^ l'he new vessel^ which might be considered as
part of the normal aging process,, are probably the source
of many symptomatic juxlapaptllary and peripheral idio­
pathic neovascular membranes.
The general guidelines for laser pholocoagulalion of
extrafovea I and fuxtafoveal choroidal neovascularization
associated with A M P and POI IS are used in patients with
idiopathic choroidal neovascularization More recently
anti V EG f antibodies are being increasingly used to treat
all types of choroidal neovascularization.'1'!
3.16 Continued
L—Q : La где notched i-еггшь d e licti ment of lh e retinal pig­
ment epithelium iK ft.i caused liy an oci:ull j и s lapap i 11ary
sub-KPE new-vessel membrane larrowa, L| in л 50-year-old
wom an wilh- skin changes compatible w ilh pseudoxanthoma
elaslicum. ih e had angioid breaks Jn the ri^hl eye. Visual
rituily vi-ан 2 OL-'.'AO. K a le ftnely mall led арреатапсе of lhe ele­
vated RPE and Ihe i;harp outline of 'he margin of the detach­
ment of the RPE {L ]. There is minimal sertAis elevation of
lhe retina surrounding the base o f Lhe К Г Е delac hment. N o
definite anpioid streak is visible. Several minutes following
fJuorest:ein injection ihete was faint fitiifirtry of the sub-KPt
enudale. O ne-hour an^io^Tam showed diffuse staining of lhe
sub-HRE exudate (N). This slow development o f staining indi­
cated lhe m obable presence of hi^h prolein concentration
and hJood pigment in the s Lib-К PE sprite. Note absence of
slainiпц, in lhe area o f lbe noluh iarro w Mj. Six weeks later
the patient developed circinate deposits along Lbe margins
of lhe RRE detach men I i{>:. This Was deft n i L<* evidence of
Lhe presence of choroidaf neovascularization somewhere
benealh the RPE detachment. Ei^hl days following Lhe р1ю-
loyraph in D lhe palienl develOtled evidence of bieedin^ m1o
Lhe area of RPl: delachm enl IP. Note lbe il uid ievel of bfo<jd
larrowsl. M anv monlhs later ihere w ere prominent neotascu­
ta r Lrunka (arrow, Q ) and lhe RPE deflnicbment had cul lapsed.
Eccentric Type
Solitary subretinal hematomas and disciform masses may
develop anywhere in the exlramacular region, in one eye of
patients whose eyes are olhenvise normal (I'igure 3.36G-
К ).,||:и'' Many of these probably arise in old postinHam-
uiatory' or traumatic scars lhat are hidden by Lbe disciform
detachment.
P E R IP H E R A L ID IO P A T H IC SU B-R PE
N E O V A S C U LA Rf ZATI O N
Multifocal areas of bleeding benealh the pigment epi-
Lhelium and relina may осей г anterior to lhe equalor
im w liy in lhe temporal half of the fundus tn elderly pat-
ipntSiJH-Sjii2j*i^ials?(-5|a lhe&e patients may or may nal
have evidence of AMD [Й^цгез 3.2S and 3.37J. These
hemorrhages probacy occur secondary lo blEeding from
neovasculartiatloti, which has heen demonstrated in the
sub-KPL region in lhe area of the inner collagenous por­
tion of iimch's membrane in approximately 4 JW of eyes
al autopsy near lhe ora serrala., particularly in the tempo­
ral sectors.' " " These vessels emanate from the adjacent
pars pEana region.-^11 Subrelinal scarring caused by these
peripheral hemorrhages is oflen discovered on routine
eye examination. Luge sub-RPH hematomas or hbrovas-
culiir masses may be mistaken for melanomas [E'igures
3.26 and 3.37J. rxlen ston of lhe suh reti nal blood into lhe
vitreous may cause die palienl lo seek an eye examina­
tion. Occasionally loss of central vision occurs because of
gradual migration of subrelinal exudation posteriorly inlo
the macular region. Abrupl loss of vision may result from
large serosanguineous RPK detachments exlending from
the posterior edge of the peripheral neovascular complex
into lhe macuSar area where a rip in die RPE may occur
(E:igure 3 37] Asymptomatic palients wilh no
visual impairment can be followed with lhe expectation
Lbat most w ill eventually show resolution of lhe bleeding
spontaneously. Transsclera! ciyореху, laser pholocoagu-
Ealion. and anli-VI-ХЛ therapy are effective in controlling
the hemorrhage and exudalion if the condition progresses
(E'igure 3.37К and L).
3..-J7 Idiopathic peripheral choroidal
neovascularization causing large lears in the relinal
pigment epithelium and loss ol" central vision.,
A—D: Large serous relinal pigment epilEielium iK PEl deLacb-
monl and К HE. luar in lhe 1етротл1 m acular л пел ol lhe left
eye ol a o7-year-old wom an with subrelinnl and sub-KPt
hemorrhages in LE^e temporal perlp fery of bo-lh eyes. Note
equatorial hemorrhages in A lh al extended posterior!^ to
lhe temporal edge of the т а с Ы л of the light eye. In Ihe lefl
eye aldng Ihe temporal odge of lhe m acula I hone was л ser­
pentine RJ'L 1елг iaTrows. Ill at :bu posleiiof edge o f л largp
peripheral sen sanguineous RI-’E detachment. Angiography
revealed striking hyperfluonescence in Ibe area of the tear
(C and Dl. E^our years CTeviously she had а renal 'ransplanl
because of renal failure related to Eight-chain disease.
E—f: A 7?-year-old man developed sudden loss, о i vision in
the lefl eye. It was caused bv rapid decompression ol a lar^e
peripherally Iпса led serosanguineous delachmenl Ы lhe K P t
through a large R PE rip in Lhe nasal edge of Ihe R PE detach­
ment into I bo su Eire! inn I space in lhe т л е й I л IE and Fi. His
visual acuity was 20/300. Ko1e the early hyperfluorescence
in Ihe лгеп of" lhrL large RE"E tear (arrcSfc F:- лп-d the movurnenl
ot dye through the hole 'arrow, <Li) into Ibe siibrelinal fluid in
Lhe macula. The HuE>retinal fFuid in the macula had resolved
2 '/j Weeks later IIH and 11 but the lar^ge peripheral serosa n-
gufneous detachment uf the R PE ren am ed (arrows, Jl. Note
absence ol evid en ce ol гласиlaf degeneration and rolled
peripheral edge of К PE (ear (If. The source o f the bleeding
and the serous exudalion was probably a choroidal neovas-
cular membrane in the vicinily of the equator tem poralIv.
К and L: Idiopalhic peripheral choroidal nooyascul^rlialitin
associated w ilh exudalite relinal delachm enl exI ending into
the m acula IK: was successfully Irealed w ilh pholocoagula-
liun [L),
lA - U L D U i l M - y 4 JI ] J r . b J a n e y k i r k ; t - l f r u m С 1 п ч :п .l i k J V j n i i r . . ' i
A N G IO ID ST R EA K S A N D
A S S O C IA T E D D IS E A S E S
Angioid streaks are irregular. rad tali ng, Fagged.- taper­
ing lines thal extend from the peri papi Itaiy ares into the
peripheral fundus.'1" u4 ]Ъе term "angjoid' Was chosen
because of the ophthalmoscopic similarity of these streaks
to blood vesseEs. rl"hey are caused by linear cracklike dehis­
cences in the collagenous and elastic portion of Bruchs
membrane (Figures $ф З-1^3),5г*гИЙ Near the optic disc.,
they are often interconnected by circumferential breaks
in Bruch's membrane. Larly in the disease the streaks are
sharply outlined in color, varying from reddish orange to
dark red or brown, depending on the pigmentary charac­
teristics of the underlying choroid that becomes visible
through the thinned R P t overlying the linear defects in
Bruch's membrane, l ibrovascu!ar proliferation from die
choroid may grow through the breaks in Bruch's mem­
brane and elevate the surrounding RPJi [Figure 3.4UCJ-E).
Jhls causes blurring and In some cases totally obscures the
streak margins. The protiferative changes are often promi­
nent along streaks extending into the macular region, and
they may be associated with slowly progressive m acuta г
changes and loss of centra! vision. Abrupt loss of vision.,
however, is more frequently caused by serous and hem­
orrhagic detachment surrounding areas of choroidal
J.38 Angioid streaks and pseudoxanthoma e East it urn.
A -С: Ib is 25-year-old man's visual atuiLv was normaE. Note
Ihe clum p of pijym 'nl and rnulLiple w hile £uhjelin<il tfys-
1лI line bodies {inferior Lo Ihe optic dine :Л and ]J, arrows:.
AngiogiapEiy showed irregular hypeifluorescence alone, Lhe
tourac Dl 1lie angioid slroritu ltl.i.
D and E: Large pigmented angiold slraaks. N o he peau
d'orange lem|>oral lo the left m acula (Ё).
f : Angioid itnealti Hop arnjwl, multiple calcified drusenlike
i t n k l u i e '.Exjltom arrow j, and peau d'orange ( hanpo.
G and H: H-eticular m acular dystrophy, angioid streaks;, and
cryslailine bodies 'iarroVh .
!: Anjjioid streaks and orusefl o f o p tic dfsc.
j and K: Psfeiudosanlhoma е1 ?вЦ си т ir> anlccubilal fossa
and neck.
neovascularization that have grown through the angioid
streak* into the sub-RPE or subretinal space in or near
the papi Elо т acu Ear bundle region [E-'lgures 3.39A and С
and 3.41 A-С]. Occasionally patients will develop Eaige
areas of serous detachment of the EiPfc adjacenL to these
neovascular membranes [t'lgure 3.42A).1' Because of the
brittleness of Bruch's membrane in patients with angioid
streaks, they may develop loss of centra! vision Secondary
to choroidal ruplure and submacular hemorrhage follow­
ing nisignificant trauma (figure 3.39L and
 Angioid streaks may show irregular hyperfluores­
cence during lhe early phases of angiography and varying
degrees of staining during the later phases (E'igures 3.33C,
3.39J:; 3.421 L and 3.43L*).SU,I,J:' '" ' hi some patients With
heavily pigmenled choroids, ЬсЯ¥еуе£ well-defined angi­
oid streaks may be barely visible angiographically (figure
3.39D). In other patients, angiography may be helpful
in delecting RiJh alterations along small angioid streaks
before they are visible ophthalmoscopically. Angiography
is also о Г value in delecting choroidal neovascularization
(E'igures 3.39E3, I>* and I, and 3.4] ]. In some cases of occult
choroidal neovascularization, however, angiography may
(ail to show evidence of new vessels (Figure 3.42A-1-).
I listopathologically, angioid streaks are discrete linear
breaks in Bruch's membraner which often shows extensive
calcific degeneration (Figure ■3i43G).saa',S2S,,5J5‘5afi Thifi may
be associated with changes in the choriocapillaris similar
to those seen in patients with macular drusen. Fibrous tis­
sue aloner capillary proliferation, or bolh may grow from
the choroid around lhe edge of the dehiscence in Bruch's
membrane inlo Lhe sub-RETE: space. It is these capillaries
that are the source of serous and hemorrhagic detachmectt
in these patients.
Clarkson and Allman ,^10 in a diagnostic workup of
50 patients with angioid streaks, were able to establish a
related systemic diagnosis in 25 patients (50%J. In 17 of
these palienLs the diagnosis was PXL, 5 had Paget's dis­
ease, and 3 had sickle-cell hemoglobinopathy. Ihere Ls
evidence that angioid streaks may be pathogenetically
related lo Lhlers-Danlos syndrome.511,1 lhe evidence is less
convincing for tnany other diseases lhal have' occasionally
occurred in palienLs with angioid streaks.'''"
3.39 Angioid streaks and pseudoxanthoma elastic urn.
A .111[< li: Choroidal neova scutari Italian 'iarrayi, Л. extend­
ing from [he edge of android s[r-eak and causing submacular
hemorrhage in a patient wiLh pseud^JLimtEidrna feUsHtLlm.
An^io^irini showed new-vessel network yarrows, E3:.
С ^nd D : РлтИПййС angioid streaks in a i З-уедr-old man
w ilh pseudoxanthoma elasLicum a rd loss of central vision
secondary Lo serous detach men L o f I ho imncula lafmivs, O .
A ngioginm showed evid en ce of a choroidal neovascular
топлЕмапе (arrows, l>i original ing a1 lhe siLe of inn angioid
slroak. N olo in Ihis paiiunl lhal I he angiogram showed m ini­
mal alterations of Iho angiographic paLLern along Lho course
□! lhe streaks.
f and F: Subjtrtlfral iiemorrtiage afler a minor b lo w Lo lhe lefl
eve of й 23-year-old wom an with muEliple anjjioid streaks
and pseudosanlhoma ola-sLitum. Nole vertical choroidal
rupture on lho nasal fidjge of [he fovea and partly reabsorbed
suliretinal blood ILI. fluorescein angiography sЕюwed irreg­
ular rluoresdfcio^ alonj* [he course of the imgioid Streaks
and pTominent fluorescence in the -region of lhe choroidal
rupture (h. l'h-c brilllenes-ь of КпесЬ'н memEirane caused by
pseudosanlhoma elasticum was prebafsJy responsible for
lhe development of a choroidal ruplure following n.(lativel\
minor [тпшпл. Thin pa lien I subsequently recovered norm j I
visual acuiLy.
G -L : SuEjreLrnaf neovascu larizal ion farrows, С a rd I) in Lho
riul+i I eyo of Ihis m iddle-aged w o m ;ir wilEi pseudoxanthoma
elasticum, angioid slreaks, and pattern dystropEiy (C and HE.
Laser photocc1aglljalion uealmenL i Kj was successful in eradi­
cating lbe noovasculariz.iLion :L'l.
.ingifjiri ifn.nJr^ mni Asso&jjted Dfprtirftfs 145

P S E U D O X A N T H O M A E L A S T IC U M
(G R O N В LA D -ST R A N D B E R G )
t’XE is a systemic disease named for its cutaneous coun-
LerparL, which is charactered by the development of
confluent yellowish papules thal give the skin л "plucked
chicken" appearance on the flexural surfaces in the neck,.
antecubilaE fossa, and periumbilical ja*a.ni'?,513-'3il*
I Lis-tjologically, these changes are canned by degeneration
and calcificaLion of lhe elastic tissue of the dermis. rLhese
changes may be associated wilh premature calcification of
Lhe large arteries of the extremities and with gastrointesti­
nal bleeding. I'XY. is a hereditary disease whose causal gene
is the adenosine triphosphate-binding cassette, subfamily
С {CJTR/MR_PJr member 6 [ABCC 6J gene, Which encodes
mu Ilid rug resistance-associated pro Lein-6 (M R PS).^ ' En
addition to streaks, other associated fundoscopic findings
in diese patients include the following:
* Peau drorange pigmentary change. Widespread areas
о Г mottling of the fundus caused by multiple, indis­
tinct, confluent, yellowish lesions at the level of ihe RPli
that have been likened to that of an orange skin (peau
drorange).‘'^ '‘ULl Ihese may become prominent in the
fundi in childhood before the develop menl of angi-
oid streaks [E'igure 3.3SE: and F ),5'■ ul Ihey are usually
most apparent in [he mid peripheral fundus, particu­
larly on fhe temporal side in older patients with ETXK.
'['hey are seen less often in patients wilh angioid streaks
associated wilh L]agetrs disease and sickle-cell disease.5,1?
1.40 P s e u d o x a n th o m a e la s tic u m a n c l p a tte rn
dystrophy^
A and В: Appearance of purrclale brown mgjnttijt spoLs »f
fundus pulvurulunLuK Lyptf ut" pfijLem dystrophy in lhe т-асиЗа
□f lhiH rmile wiLh angioid streaks and p^trudnsanlhoma ela-s-
Licum iL5'.
C: l^ilienL with pseuduxrinLhumn eliistacunn And angjiuid
streaks shows butterfly Lype in the m acula and fundus fla-
vima-LU talus Lype of pntlern tfvslrophy near lhe a.rcadHS
ia rmws I.
tr a n s itio n fro m o n e ly p e o f p a tte rn d y s tr o p h y lo
an o th er.
1) jind E: Initial f'Unrfus pukerulenlus Lype of pattern dysLro-
phy with granular brown du[s (D ) progress'd to develop yel-
l(iw viLellifuim type of dystrophy 5 years later ‘ L.i.
F and G : Extensive distribution ol" Lhe pattern dystrophy even
[jLiIside the гп-асиЗа.
H - L: This -tS-yeaf-uld matei h-ad o plic nerve drusen, anyioid
slieafcs.. buHerfly pattern dystropEiy and progressive spnnla-
neuus relinai IHgjrienL epil helium atrophy in bolh eyes. The
fleck!- of pattern dystrophy Khtiw Eirilliant autoA uorescente :l
and It).
lhe histopalhologic changes responsible for the peau
d'orange appearance are unknown. These lesions cause
minimal alterations on iluorescein angiography but ibay
be associated with a diffuse speckled pattern of indo-
cyanlne green byperHuorescence, a finding that suggests
Lhal lhe orange peel appearance may be caused by an
altera Lioil al the level of Bruch's membrane,"111
* I’atbem dystrophy of the macula. Approximately
of patients iviLh [’XL ладу develop ,1 pattern dystrophy of
macula bilatemlLy.' 1 It is most frequency manifest as ,i
reticular network or a combination of reticular network
and multiple punctate pigment spots (fundus pulveml-
entus) [figures 3.3SC;, i3 9 G and ] [, and 3.40A -D ]> ^4,1
(See pattern dystrophies, Chapter 5.) Olher typers of pat­
tern dystrophy have also been noted, including vitel-
liform [E'igure 3.40E), butterfly (Figure 3.40H-K], and
fundus flavimaculatus type [figure 3.40Cr arrows),
though less frequently.r' ] N attem dystrophy may appear
during follow-up (figure 3.40Л and B] or progress from
one type Lo another over time (figure 3.40D and tij.'lh e
pigmentary disturbance js. often more apparent angio-
graphicalty than ophthalmoscopicaily.
* 1'ocal atrophic pigment epithelial lesions. Multiple
small, round, yellow or slightly pink, Rl’h atrophic
lesions as welt as discretely punched-out white scars
With varying amounts of pigment similar to those seen
in POI-IS occur commonly in the peripheral fundus of
these patients. Ihese have occasionally been referred lo
as saimon spots.
3,4i Pseudoxanthoma elasticum: progression and
choroidal neovascularization.
A —G : Til is ^-year-old male wiLh pseudoxanthoma elasLi-
cum hfld previously underieifiC l<LH?r phlfflittccmu lalitfh lo
two exlrafoteal sites o f choroidal nyovaHcuJari/alion nlon^
ihe angioid streaks !arrCrtv4ieads)h H e developed recurrence
□I the membrane (A - t ) ihal required three sessions of pho-
tadynam ic iherapy. 1л the meantime spon I алеешь Lhinnin^
and atrophy of the retinal pign>erl ejjphelftJm (fip tj i v « s
noled farrows! away from Ihe she ol" the neovascular mem­
branes, (hat gradually increased in s iie (A-С, E and G>.
А'.ПоГкюгвдсапсе jmaf^in^ d e arlv delineates the area o f lit3t
atrophy in Ci.
* Crystalline hodles. Multiple round, small- sub retinal,
crystalline bodies typically occur in the jnid peripheral
fundus or juxtapapillary area, particularly interiorly,
in as manv as 75Vo of patients (Figure З.Звй, P, and
Th ese are always associated with some atro­
phic changes of the RPF. In some cases a "laiT of UPf
thinning lying posteriorly Lo a crystalline body gives iL
the appearance of а ^еотеГ (figure 3.3SB and h).
* Hyaline bodies of the optic disc. Hyaline bodies (dru­
sen) of lhe op Liс discs occur in approximately 5% of
patients with angioid streaks and pxfi5;,j,i46-5ja [Hgures
3.3SI and 3.4UIL, |, and L). H is not as common as
believed. Acute visual loss caused by an optic neuropa­
thy may occurin these paLients with hyaline bodies.'"’ '1
* [’regressive atrophy of the ЙПИ Spontaneous atrophy
of Lhe pigment epithelium occurs in the vicinity of the
angioid streaks without evidence of, or contraction of,
choroidal neovascularization [L-'igure 3.4UA-C, E and F,
arrows).
A PXii patient with congenital со ntiituni cation
bem'een a cilioretinal artery and retinal artery has been
described.543 The inheritance pattern of l*XH may be
either autosomal -do m inant or recessive. Ciass has seen
one patient whose mother and two maternal uncles had
Paget's disease of the bone.1,D
Siclde-Cell Disease and Other
Hemoglobinopathies
it has been estimated that 1- 2% of patients with the
sickle-cell hemoglobinopathies will develop angioid
streaks (Kigures 3.40J-L and 6.59H and
Streaks in these patients have rarely occurred under the
age of 25 years. Serous and hemorrhagic detachment
of Lhe macula occurs infrequently in sickle-cell patients
wilh streaks and in black patients in general (see figure
3.55}. Streaks have been reported in homozygous sickle­
cell disease, sickte<etl hemoglobin С disease, sickle-cell
thalassemia,5’2'575,576 sickle-cell t r a i l , h e m o g l o b i n
3A2 Angioid slreaks,
A—C: Thrs 42-yea r-oid male com plained o f progressive visual
lass in lioth eyes lor 5 years. He had atypFcal breaks, run­
ning in Lhe middle of b e macula (a rmws Л and В I, fundus
pulvemlunlus-Lype pa Пип dyslnophv in bo!h eyes and several
пгепи or spontaneous sutjretinal fibrous pnsliteration vuLhoul
evidence of choroidal neovascularization {arrowheads В and
Cl. The fluorescein angiogram helped in finding Lhe angf-
oid slreaks and Lhe pallcrn dystrophy (nol shown). The skin
on his neck showtfd Ihe lypical c h a n g e of pseudoKanLhoma
elasLFiium.
Angioid streaks fn sickle cell disease
D and E: Angioid streaks in a black patient vuiLh skide-cel! С
disease. \o te tortuohilv ol veins.
;■: A n jio id sweats m a 4 I -year-old blacJi wom an wiLh sickle-
l <?3I С disease-.
H disease.1-"'1 homozygous beta-thalassemia major, ■ i .-^ii
beta-thalassemia intermedia, beta-thalassemia minor,SS]"
1,1 congenital dyserythropoietic anemia type I,1"1’ and
hereditary spherocytosis. '4 Sonte patients with sickle thal­
assemia may have PXE as well as angioid streaks.575
Deposition of iron-calcium complexes in Bruch's mem­
brane caused by excessive blood breakdown was suggested
as a possible cause for Lhe brittleness of the membrane
and angioid streaks in sickle-cell disease.1' " 1 However,
(his could not be confirmed bislopathologieally in the
eyes of a 63-year-old man With homozygous sickle-cell dis­
ease and angioid streaks.:hJ| 'Ihere was extensive calcifica­
tion of llmch's membrane but no iron deposition.
PA G ET 'S D IS E A S E
Paget's disease es A chronic, progressive, and in some eases
hereditary disease characterised by thickening, rarefac­
tion,- and deformity of the bones. The disease may be con­
fined lo a few bones or may be generalized. In ihe latter
case, usually after ihe age of 40 years, ihe patient develops
enlargement of the skull, deformity of the long bones,
kyphoscoliosis, and hearing loss (higure 3.43). ЧЪе axial
skeleton is most affected. I"he condition is often asymp­
tomatic but can be associated with bone painr osteoar­
thritis, pathological fractures, and nerve compression
syndromes, Mxophthalmos and normal-pressure hydro­
cephalus are rare complications secondary lo involvement
of the skull. "■ " 1 These patients, particularly those with
skull involvement, may develop extensive catcificalion of
Bruch's membrane, an irregular pattern of angioid streaks,
and severe choroidal neovascularization and disciform
scarring (Figure £.|Й)'519'И5,5:!5"554 Approximately 10%
or less of patients with Paget's disease develop angioid
st r eaks. : I"hose with die earliest onset of disease
and severe bone involvemenl are most likely lo develop
angioid streaks and choroidal neovascularization. Some of
these patients show mottling of the RPli in the midperiph­
ery (peau d'orange) similar to lhal seen in ГХЕ-. Visual loss
Is caused most frequently by choroidal neovascularization
but can also be caused by optic atrophy that cannot be
explained solely on the basis of bony compression. 560%
choroidal neovascularization is type 2 that grows in the
sub retinal space, similar to lhat seen in P X L POHS, and
other chorioretinal scars, and unlike the neovasculariza­
tion of AMD which grows under the ]{P L
Paget's disease is more common in Caucasians, par­
ticularly in the UK and amongst British migrants to
Australia, New Zealand, and South Africa, and in western
and southern Eiurope. though reported, Lhe disease is rare
in Scandinavia- India, China, Japan, and South-east Asia.
Mutations have been identified in four genes: the most
important is Sequestome 1 (SQSTiM J), which es a scaf­
fold protein in the nuclear factor-i:B signaling pathway. ":!
Ihere is some evidence that a slow virus infection related
to either measles (paramyxoma virus) or respiratory syn­
cytial virus may act as a trigger for Paget's disease.'"
Other potential triggers include dietary deficiency of cal­
cium and repetitive mechanical loading of the skeleton.
Bisphosphonates decrease bone turnover and are helpful
ill alleviating bone pain.
An orbilal osteoclastoma which was extraskeletal in
origin Was removed from the orbit oi" a 51-year-old with
Paget's disease. Sarcomatous transform at ion of the orbital
bone has also been reported.5bl- '
Rare Associations
Angioid streaks may occur in parents with abetalipopro-
tt’inemia.',Hs' isolated case reports of angioid streaks
A n g io id streaks an d PageL's d ise a se :
c lrn ico p a lh o E o g ic c o rre la tio n .
A —H : This Ы -year-oEd man w ith FbgeL's disease was seen
ЬюЕаияв of rccrenl I dus o f cenLraI vision in his left eye. He
had previously lust Lhe centra! vision m his righl eye fol­
lowing a m acular hemorrhage. Note lhe onlanjed cranium^
dilated LDrLuauH temporal artery and hearing aid on lhe
i iH,hI side i.A'. Them1 was a lerpmJ detachment of lhe macula
secondary Lo choroidal neovaSdLilarilatioffii in Ihe area bf
an angioid sLneak and C".. NoLe Llie prominent slneak in
E (Harrow!'. The histopathology ol Lhis streak nL Ihe site indi­
cated i:-\ Lhe arrow :> ii usLraLed in i .. An^io^r.iphv showed
hyperfluorescence alonjj, (he streaks and a large choroidal
neovascular membrane (C N V M i in (he paprllom atular bun­
dle region La nows, Dl. Xenon pE»otucoagu[atian was placed
in the area o f the C N V M (Ё^. The subretinal fluid resolved.
Fifteen weeks Inter it . however, he developed further e v i­
dence bf choroidal noovastLitarizalion (anows, F). The
paLienL (rdbsec|Lien[ly died, and his eyes w uie obtained aL
aulopsy. Histopalhokigy of the angioid slreak depipted in В
showed а break in B n ich ^ membrane (arrowj, Lh inning of
Lhe reLinal pi^menL e p ilhelium iRF’b., sub-KPt deposition of
fibjillar fiK iA o p b tlic male rial. алН he-rniation of lhe choroi­
dal blood vessels inlo 1Ke> - area of (fit1 break : . There was
some atrophy of the choriocapillaris surrounding (he break.
Von Kossa's sLain ior callcium revealed ех1елмуе calcification
of Bruch's rraSmbramJ and соЗЗа^ип tissue surrounding lhe
choriocapillaris IH.. Note Lhe alnophk relina and LEal vascu­
larized subrefinal sea*.
I and |: НЧцглеnLed angioid slneaks and submaculnr choroi­
dal neovascularization in 55-year-old physician w ilh Paget's
disease.
lA -M Ггигп <,.L-;b o n d C la rtte u fl,'' 'l
associated with pituitary tumor, familial polyposis of the
colon, congenital hypertrophy of the RPE, and Sturge-
Weber syndrome with facial angiomatosis have been
reported.;se
Treatment
]Clients with angioid streaks should be warned of the
potential risk of choroidal rupture from relatively mild
contusion to the eye. As palienls with streaks reach the
fifth decade, they are at risk of spontaneously developing
serous and hemorrhagic detachment of the retina second­
ary to choroidal neovascularization. Eraser treatment may
be successful In obliterating the neovascularization Ifil has
nol extended inside the capillary-free zone [E'igure 3.3DG-
Lj because uf ihe multiple breaks in Bruch's
membrane, other neovascular membranes are likely lo
occur. More recently; anti-VKGP treatment with InLravitreal
bevacizumab and ranibizumab has been successful and
may be safer by preventing further breaks in the Bruch's
membrane from laser. *r:i-|:J:i-
M Y O P IC C H O R O ID A L
D E G E N E R A T IO N
PalienLs wilh progressive elongation of lhe eye (patho­
logic myopia) develop Lbinning of Lhe choroid and RPE in
the macular area, '['his may be associated xvith the devel­
opment of Lilting of Lhe oplic disc, peripapillary chorio­
retinal atrophy, posterior staphylomata. gyrate areas of
aLrophy of the pigment epithelium and choroid., and lac­
quer cracks (figures 3.44 and З д а .т к и '£Н 7 Lacquer
cracks art- caused by spoiltaneous focal linear breaks in
Bruch's membrane, this mplure may he accompanied by
a small subretinal hemorrhage unassocialed With evidence
of choroidal neovascularization [E'igure 3.44L>).': l | : '
Jliese subretinal hemorrhages are usually noted during
routine examination of young patients either al the site of
or limncdialely preceding the development of a lacquer
crack, l-acquer cracks often radiate outward in a reticular
pattern from one or several areas of choroidal pig men L
epithelial atrophy [E'igtire 3.44A and В).йи Visual acuity
may be excel lent in spile of extensive atrophic changes in
the R]'h and choroid.
Most patients are In their fifth decade or beyond when
they begin Lo experience slowly progressive loss of central
acuity associated wilh myopic degenerative changes. Rapid
loss of central vision is usually caused hy exudative and
hemorrhagic macular detachment overlying small areas
of choroidal neovascularization (figures 3.44C. L. and F,
and 3.45A). 'Ihis may occur adjacent to a lacquer crack, in
an area of geographic atrophy of the К Ft, or often in an
area of generalized alien nation of Lhe RE5Ei and choroid,
l'he new-vessel membrane and the area of delachmenl are
usually small and located close to lhe central macular area.
Thie new-vessel membrane characteristically appears bio-
mlcroscopically as a faintly gray semltransiucent plaque
wilh a hyperplgmented border (E'igures 3.44C and b, and
3.45A). Ef associated with subretinal bleeding, a small
relatively round mound of RPfi proliferation may develop
as the blood clears (Figure 3.44C. and El). This pigmented
mound may obscure lhe CNVM from View.^
The relatively small size of choroidal neovascular com­
plexes in myopia is probably a function of the attenuated
blood supply lo the thin choroid. Because of Lhe smallness
of the disciform lesions, the chances for retain ing 20/200
or better acuity is higher tn these patients following cho­
roidal neovascularization than in palienls with emme-
Lropia and senile macular d e g e n e ra tio n .Forste^f12 and
L,Ult I described a Mi sod. circular, pigmenled legion
that frequently develops In the macula of middle-aged
persons with myopia (]:orsler-l'uch& spot). Cl ini cal Ly and
hislopalhologlcally, this Lesion, which typically is approx­
imately Vi disc diameter in size., consists of a localized
ingrowth of fihrovascular tissue from the choroid and pro­
liferation of the RPL (E'igures 3.44C and 3.450)/^ '['here
is limited histopathologic information concerning choroi­
dal neovascularization in myopic degeneration.
3.44 Fundus changes in high myopia*
A: Lacquef cracks ^xrow J.
B and C: Smull lacquer crack (arrow, S) 5 months prior lo
developing ыгпиII type 31 subretinal tieaVasiSLilar п геш н ип ё
surrounded by л pigmenLed halo.
D : 5jmcn11 subretinal hemorrhage (arrow] I Ьл I subse­
quently г lea red without show ing evid en ce of subretinal
neovasculari zation.
L and F: Snbrelinal neuvascuIлriглLid n ^urowsj.
G : Kidmen Led disciform scar (arrow; at edge o f geographic
atrophy of U P t nnd choroid.
14 and I: Natural historv o f progression o f j uxlapapi I lary
geographic atrophy o i the relina and choroid over a T3-year
period. Nole disappearance erf small pigrnenlud disciform
scar 'w h ile arrow-1 and Lhe development of a focal slaphv-
luma si mu haling an optic disc !black anow'i.
]: ldiup<ilhic retinal detachment w ilh CortCave cunfigura-
litin within a macular staphyloma !arrows! in a pa lien I
who recently developed blurred vision in the righl eve.
Kiom icroscopy and fluorescein angiography revealed no
cause for the dieEachment, w hich may be related (o vilnecweLi-
пл1 traction.
K: К h^m ato^enous m acular detachment in the right eye
caused by a m acular hole {МЩ&Л in л patient with bilateral
fUlctapapillajy and macular slaphylomala.
L: RhegfnaflSganous delachmenl of the retina in lbe macula
лrtd param acular area caused by a small mund fuxtapapil-
lary retinal hole 'iarrowj.
'l'he ill frequency of development of serous detach-
menLs tn these patients and the frequency of occurrence of
choroidal neovascularization tn middle-aged rather than
older palienls suggest that Lhe new vessels from the cho­
roid in mosL patients would be more likely Lo grow inlo
the subretinal space (type !l neovascularization) rather
than ill to the sub-RPfi space (type 1} (I'igure 3.43EU).
Muorescein angiography may demonstrate abnormal ly
slow choroidal and retinal blood flow in Lhese palienls.
Angiography is helpful in identifying; and locating the site
of choroidal neovascularization in palients who develop
serous and hemorrhagic macular detachment (Figures
3.44F, nind 3.45-ti and C).
laudative detachment of the macula must he clearly dif­
ferentiated from a localized detachmenl caused by a macu­
lar hole or a minute, usually round, retinal hole that may
be in the paramacular area in myopic persons with pos­
terior staphylomata (Figure 3.44К and E.). Bio microscopy
is usually required to find these holes. Fluorescein angi­
ography is helpful in distinguishing this rheginatogenous
detachment from an exudative detachment. En the former
case, no evidence of fluorescein leakage from the choroid
is present. 'E'hese detachtnents are relatively stable and in
some cases may spontaneously resolve.1-'1: A chronic shal­
low serous delachmenl of the macula may also occur in
some myopic palienls with fuxtapapillary and macular
staphylomas in the absence of SLihrelinal neovasculariza­
tion, retinal hole, optic disc pit, or angiographic evidence
of a leak at the level of the RPE [ligure 3.44J) ]Ъе cause
of this shallow, smooth-surfaced. and lii some casts con­ 3.4 "> Cho roidal ne ovasc ula riza ti(in i n high myo pia,
cave retinal detachment is uncertain, but il may be caused
A -С: iE*roii? detachm enI of Ihe macula causcd by cho­
by occult vitreous [Faction in lhe presence of lhe staphy­ roidal neovascularization at Lhe margins ot an area ot cho­
loma.. That some of these may be a macular schisis rather rioretinal atrophy in a 30-yea*-old man w ilh Elijah myopia.
Lhan a retinal detachment or a combination of bolh has Note Ibe pigmenL ling ■arrow, А) л I Lhe superior margin of
been identified with Lhe use of high-resolution O Cl' Lhe aLrophic t horoidal lesion. Angiograms showed evidence
[E'igure .3.4511 and ]). Most recent Ly.- л localized choroidal of a small choroidal neovascular momljfan-E:- (C N V M : arrow:
on the temporal edge of lhe capillary-free ^one of Lho foveal
excavaiion termed unilateral myopic choroidal excavation
region i!E31. 1he C N V M and its feeding vessels were I пса Led
or ectasia has been noted in myopes who complained of
with argon laser photucaaguEation HQ. Two years alter pho-
melamorphopsias {E'igure 3.45J-L). Spectral domain OCE' Locoagulalion UealmenL the patient^ visual acuity was 20/20.
demonstrates one of two appearances: lhe chon) idal exca­ D: HisLopathoEogy of subrelinal lype II fibrovascular m em ­
vation involves the outer retinal layers up lo the external brane ■Horsler-Fuchs spot) in Lhe macula of a hjghly m yo­
limiting membrane [E'igure 3.45 к and I.), or il involves pic eye. Note lhal lhe I i bnjvascu I a г plaque u rro w i in lined
only the RPE accompanied by an optically empty zone posteriorly by an inverted layer of retinal pigmenl eprLheEium
between the photoreceptors and the ЙР£.61М17 The exact (KF’t i separating lbe membrane from the native KL^L Hype ill.
E: M acular region and posterior slapEryloma in a highly m yo­
cause of these excavations is hitherto unknown; il is usu­
pic eye. N trie the ejdreme ihinness of Ihe choroid and nela-
ally located in lhe vicinity of the fovea, not always under
Lively noim a! overlying sensory retina.
the foveal center.
The chorioretinal changes in high myopia may not be Myopic macular schisis.
confined to the posterior pole. Cobblestone degeneration F—I: PosLerior staphyloma, lacquer cracks, and myopic cres-
ccnl in n 4S-ye.ir4jld w om an With 20/30 vision in lhe right
and lattice relinal degeneration may be presen I in approxi­
eye. and 20/50 -1- in Ihe lefl -eye :F--N:. The EefL macula bad
mately 15-30Яъ of eyes.ul'11 ■lл lice degeneration is more
Ctpyopic schisfe w ilh si^nificanl KlfoLching ol lhe m i lor plexi-
common in eyes wilh mild than Severe! degrees of high Готт region and ganglion cell layer fl). The posterior hya­
myopia loid was sLill attached w ilhoul exerting significanl LracLion.
Il is still unclear whether Lhe chorioretinal degenera­ UpLical coherence lom oyraphy findings and the visual acuity
tive changes in progressive myopia are merely second ary were unchanged a vear later.
bioinechanical changes caused by progressive expansion Choroidal excavation in myopia.
of the scleral coals of the eye in response Lo normal intra­ f—I : This 47-year-old, й-D m yopic Asian wom an bad a vision
ocular pressure or whether ihey Hire an integral part of the of 2& 2 5 . Several areas of choroidal excavation ^ectasia:
genetically determined abiotrophy."1 1 Myopic degenerative were seen (K and L . Some of Ihone siles have Eieen known lo
changes affecting the posterior pole may occur in some develop choroidal neovast ularizaLion ibal responds Lo anli,-
patients with only modest degrees of myopia and enlarge­ vascular endothelial growl h M d o r LneaLment.
ment of lhe eye. ContrariwE&er other patients with high 11—L l-
i iurru-у .jl LJr. K. hl.nl'jv j-ii unil.
degrees of ocular enlargement may show minimal degen­
erative changes. Although choroidal neovascularization is
more likely to occur in eyes wilh some degree of myopic
degenerative changes in the fundir it is nol solely related Lo axial elongation of the eyebalE probably results from a
the axial length of Lhe eye or the presence of degenerative combination of altered fibrillogenesis and mechanical
changes."'" J have seen il occur in patients wilh only mod­ expansion.
erate myopia and minimal evidence of attenuation of lhe 'l'he guidelines for laser pholocoagulation treatment for
RPH or evidence of a posterior slaphyloma. Spilznas and subrelinal neovascularization caused by other diseases are
Bober have demonstrated lhal the predilection for devel­ nol necessarily applicable to treatment of this complica­
oping idiopalhic posterior subrelinal neovascularization is tion in patients wilh myopic degeneration, 'lhe extreme
directly proportional lo the degree of myopia in patients thinness of the choroid and Bruch's membrane in eyes
wilh myopia of 6 D or less. When focal atrophic lesions with myopic degeneration (E'igure 3>45H) makes them
of the К L3bi in the macula accompany Lhe neovasculariza­ particularly vulnerable Lo mechanical effects, including
tion in Lhe absence of other myopic degenerative changes those induced by photocoagulation. Attenuation of the
tn patienls wilh high myopia., il may be impossible lo choroid is pFobabty also responsible for the tendency for
determine whether the atrophic lesions and the new ves­ subrelinal ne(*vascular membranes lo remain relatively
sels are a product of focal myopic chorioretinal degenera­ small. 'Ibis., together with the predilection in these patients
tive changes or a prior episode of asymptomatic multifocal for pholocoagulation scars lo enlarge, suggests that pho­
choroiditis. locoagulation treatment of' subrelinal neovascularization
Kunala and 'Jokoro induced axial myopia associ­ in these patients is of limited val Anti-VLCK agents
ated with scleral thinning experimentally in monkeys work very well and cause prompt regression of myopic
by occluding the ipsilateral eye."''1 Ihey concluded that choroidal neovascularization and are lhe treatment of
alteration of fibrillogenesis in the sclera is Lbe key fea­ choice presently. Pholodynamic therapy is also successful
ture of scleral thinning in lid suture myopia, and that in most cases.
 Successful repair of a m acula detachment caused by
□ small posterior hole can be accomplished using a vari­
ety с f special scleral buckling techniques, vitrectomy, and
iniravitrej] injection of air o f gas (Figure 3.44J—L ) '
There: is little evidence that scleral reinforcement proce­
dures prevent or lessen Lhe effecL of choroidal degenera-
Lion and neovascularization.""'1
PRESU M ED O C U LA R
H IS T O P L A S M O S IS S Y N D R O M E ____
Woods and Wahlen?JS described a clinical syndrome of
serous and hemorrhagic detachment of the macula associ­
ated with multiple peripheral atrophic chorioretinal scat!i
and peripapillary chorioretinal scarring that occurs usu­
ally in healthy patienLs between 20 and 50 years of age in
the eastern half of the USA (t-'igures 3.46-3.53 ).6Jli There
is considerable evidence that the multiple chorioretinal
scars are probably caused by a mild or suhclinical systemic
infection with tm to p ltffliit ca p su ia tu m many years before
the onset of macular detachment and visual symptoms
lhe loss of central vision is caused years iater by choroi­
dal neovascularization occurring at the site of one of these
sear s . ^ ' M ' 'Ihe average age of patients seen at the
iiascom Palmer Lye Institute with symptoms in the first
eye was 4(3 years and in the second eye approximately 44
years. 'Jhis syndrome occurs infrequently in black
persons.11,3*'1'^
ihe patient's general physical findings are typically
normal. Approximately 50% of patients show a posi­
tive skin reaction to intracutaneous injection of 1:1000
histoplasmin. Most patients show a 3+-4+ reaction.
Complement-fixing antibodies are demonstrable in only
1 (5—G of cases.:"t0 Check and associates1^1 demon­
strated that lymphocyte stimulation by the yeast phase of
tlulupiiKmti antigens was more sensitive than either the
skin lest or serum antibody test in these patients. Can ley
and associates0"11 have demonstrated evidence of a hyper­
active cellular immune response lo histoplasmin antigens
by lhe lymphocyte transformation technique in patients
who develop disciform complications, lhe re is a higher
frequency1of the I II.A-R7 and IH_A-DRw2 antigens in these
patients with disciform lesions compared to healthy per­
sons. Salients with only peripheral atrophic scars also have
3.46 Pathogenesis о fa disci form detachment caused
b y focal choroiditis.
>- .11 I': i ■i dilib, A r damages [he choriocapillaris, retins I
pigment epithelium :RPb . and ВтисЬ'ы membrane and pro­
duce* an cxuditCivo detachment of lhe retina, L5, or type
I] aubrulinal neavasLulnfizaLion and hemonfh;t^e nLo lhe
Rubretinal зрлсе, C. A n y of thtse IhrM.1 Hinges- may Ц вЫ чве
leaving either a focal area of atrophy o f the KPL, ЕЗгисНЧ
membrane, and dtoroiid LL.1: (H, in the case of subreLinal
hemujrha^e, a disciform tear, & Eilher :n the absence of
further inflammation or under the influence of recurrent opi-
■
: i "- i i !' :i himmal ion, 11■■■с hi )mi da I Ы )od \ : s.i ......i г d-
inj$ an alrophic choroidal scar (D) may « c o m p e n s a te and
cause serous exudation. cboroidiil neovascularization, and
transient s № № deladimEfnl erf the rulina It.. This in turn may
result in hemorrhcigic detachmenl of lhe rcj-lina (f) and a di-s-
ciform гелг IfJj.
a high occurrence of ILEj \-DRw 2. but not 111A-Ei7.'f,,u":,ir
'Ibis relationship of patients with PGH5 to HLA-DR2 is
not found in patients with multifocal choroiditis and
panuveitis ( pseudo-PO ElS].L1' Chest roentgenogram evi­
dence of healed histoplasmosis is a frequent finding. Focal
calcification in the liver and spleen may occasionally be
demonstrable Elarelv is Lhere evidence of active pulmonary
histoplasmosis.
Sudden blurring of vision, metamoiphopsia, micropsia,
and a positive scotoma in one eye are the initial symptoms
in most patients. As many as 25% of patients note the onsel
of symptoms at times of unusual emotional stress.'"',0 'lhe
anterior segment and vitreous are free of evidence of inflam­
mation. A localised serous or hemorrhagic deLachment of
the retina involving the macula is the most frequent find­
ing (E'igures 3.4 6Ei and С. 3.47Л and C, 3,45К E, and L and
3.4УС and G). Usually in the parafoveolar region there is a
poorly defined, round or oval, slightly elevated, light gray
subreltnal lesion Lhat varies in appearance. Frequently a
darker gray, round or ova! ring of pigment is present within
ibis light-gray area (llgures 3.47A and C). lhe hyperpig-
menlation that accompanies the choroidal neovasculariza­
tion in patients with ПЙН5 is indicative of growth of Lhe
new vessels within the sub retinal rather than Lhe sub-RPEi
space. (See discussion of type I and IE choroidal neovascu­
larization in Chapter 2 and I'igures 3.46 and 3.52.)
(A facal sharad.trs -ff edisnforrn Явде 'D■ Fccal chofodhib -pred safarm sL^ge
I I
Invtf'лапЕпГ of picjrent eDilheILn and chtfiscapdlsis hercodynani;; and factors

I I

•■
•r;i~Г "i -' |

Щ
Зег-сиь c sa to fm геИ в d erBon m eiL iL 5e™u& reliral dEiachTenri ard SLbft:n£; RK'/abCL^ariHlion туре 2

Hemorrhagic dibcrfarrn relinal cietacfvrent Hemorrhagic disciform relinal Ье1асЬтет

FibnavBsculfdiLcirom scar
 Varying amounts of subretinal blood may be р г с Ш sur­
rounding lhe margins of this dark halo. Ihis pigmenl halo
indicates the probable presence of a tlNVM, (he derails of
which are often obscured from biomlcroscopic view by the
presence оГ cloudy subretinal exudate, lhe chorioretinal
scar from which the neovascularization arises is occasion­
ally visible either beneath or at one margin of the lesion
([■'inures 3.47A and lv 3.4 а К and 3.5 2А]. In some cases a
larger oval, round, or tongue-shaped diffusely greenish-gray
membrane or mound is present in lieu of the pigment ring
figure 3.47Г). Jhe pigment ring or mound is caused by
reactive proliferation of the RPL as it attempts to surround
and envelop the sheet of choroidal new vessels entering the
subretinal space al the edge of a focal scar (see discussion
of pathology tn a later subsection). Lxudalive and hemor­
rhagic delachmenl of the RPE: occurs infrequently in these
patients. When it occurs, it is usually in patients 50 years
of age or older, in POMS the exudation and bleeding occur
primarily beneath the retina and nol beneaLh the RPt. ih e
С№ /Ц niay be confined to the area of the pigment ring, or
Et may extend outward from iI into the surrounding subreti­
nal space. This further extension of the neovascular mem­
brane is usually evident as a gray-while semitranslucent
or slightly pigmented membrane biomicroscopically sur­
rounding the pigmenl halo In a few patients the area of
the choroidal scar and neovascularization may be so small
that it caEinot be visualized biomicroscopicalEy beneath the
serous relina! detachment. Jhe angiographic findings may
simulate Lhal seen in patients with ICbCJ. In some cases
the retinal detachment overlies an atrophic choroidal scar
in the absence of a demonstrable new-vessel membrane
(E'igure 3.47D and ti). A tongue-shaped neovascu-
lar membrane arising at the site of peripapillary scarriEtg
(Hgure 3.40L) may be the cause of macular detachmeEtt.
lYripapillaiy relinal detachment and oplic disc edema with­
out evidence of subretinal neovascularization may occur
occasionally.1 Multiple sites of retinal detachment
3.47 Sero us and he mo rr hagf с delachment о f th e
macula in the presumed ocular histoplasmosis
syndrome.
A—£.: SEnosfen^jinBdLiS rd m a' сГйасЫйепI irt I n v i b L i t L Note
fain I pigment halt) S id N co d around j^nny scar iA;. subretinal
пео!л'51;и(Й(Г membfane iantjw, B), яп-cJ linear, oonf luc?nl. uqua-
lorial distribution of peripheral d"ionors?lin;il scars III).
0 and E: Recurrent serous delachmenL of lhe relina larnjw-
headsr El without other evidence и I subretinal neovascular­
ization surrounding a local atrophic chorEDredEnaf scar.
Serous retina] detachTnenl caused by a large Kubfoveal
hyjKTpi^menled lype II subrelinal n eo vascu lif membrane
i^niriil arrows'' arising from an eKtiiifoveal chorioTeLinai scar
[large arrowj. This patient would be a good candidate far sur­
gical excision of Lhe membrane. (5e£ l iLjure .Э.52А-1.
f t - 1: Spontaneous resolution of Keniorrhaj’jc detachment of
lhe macula secondary I о a choroidal neuvast и 1лг membrane
(C N V M ! in lhe center of the т л и la in а 28-тоаг-оЫ Vi-omni:
(G and H). Visual acuily was 2(У200. Twelve years later (If
the visual acuity was 20/30 in spile of the subfoveolar scar.
1 See Figure 3.5 3. i
J-L: Sponlanuoub resolution of serous and hem orrhage
detachment ot Lbe macula associated with a large extra/oveal
CK'ViVi (arrows, K1 in a 4:5-war-old woman. Thu patients visual
acuity inilially wan tij^hleen months alter resolution of
tfte blood and exudale :iie vis-Ltai acuity was 2&'40 I.L I.
overlying C.NVMs may be presenl in the same eye.
t>ccasionally, serous and hemorrhagic retinal delachmenl
develops al the edge of a peripherally located chorioretinal
scar. Hgure 3.50 (A and B) illustrates one such patient who
was misdiagnosed as having a me!ant)т а . The disciform
macular scars that develop after (he resolution of the sub-
retiEtal blood and exudate vary’ in size., shape, and color. In
general ihev are smaller in diameter than those occurring in
older patlenls wilh drusen. Occasionally, however, ihey may
exceed 2 disc diameters in size.
 Other important features of PO HS include peri papil-
Eary choriorelinaE scarring and the presence of m ultiply
often sharply circumscribed, round or oval, focal, white.,
atrophic scars scattered throughout the fundi (Figures
3.47A and C 3.4tfA and C, and 3.51 К and G). lhe focal
scars vary in size and degree of hyperpigmenlation. Most
are W -l disc diameter in si/je or smaller. Some involve
the full thickness of the choroid and lirti and present the
biomicroscopic appearance of white, punched-out, atro­
phic lesions (i'igure 3 .4 8A and C ). A large choroidal vessel
may course through some of these lesions. Other lesions
are more deeply located in the choroid and involve the
R p t to a lesser degree. The)1 have a more yellow or orange
appearance and may be mistaken for focal nodules of
choroidal in filtration. Some Eesions show a combination
of these two cltangesr that is, a focal atrophic lesion sur­
rounded by an orange halo. Although RPli proliferation is
often conspicuously absent in these lesions, black pigment
may occur within or at the margins of the lesions [E'igures
3.47A. 3.4 S C and 3.51F}. ibe lesions may be located any­
where in the fundus. Occasionally; they are arranged in a
curvilinear row near the equator (Figure 3 . 4 7 C ) . in
some patients a continuous band of depigmentation may
extend around the equator in one or all quadrants. Ihis
equatorial distributton of lesions may occur in as many
as 5% of patients with PO JI5. Similar streaks have been
noted in patients wilh multifocal choroidal scare, vilri-
tis, and no evidence of histoplasmosis (see discussion of
pseudo-POl-IS, pp. 5 Acute visual symp­
toms in a few patients with PO HS may be associated With
swelling of the optic disc and enlargement of the blind
spot in the absence of any evidence of suhreti nal neovas­
cularization .''"14" i he symptoms and disc edema usually
resolve spontaneously and leave evidence of juxlapapil-
Laiy scarring. (See discussion of reactive lesions simulating
papilledema in a subsequent section.)
Fluorescein Angiography
Angiography typically reveals evidence of a cartwheel- or
seafan-sbaped CNVM in the area of the subnetinaI gray
or pigment ring lesion [E'igure 3.47E1. I L and K). The
neovascular membrane may be confined lo the area of
the pigmenl ring, or it may extend well beyond its bor­
der. Cood-quality, early stereoangiograms are essential lo
determine accurately the location, size- and proximity of
the CNVM to the center of the fovea. In some instances
blood or cloudy exudate overlying the neovascular mem­
brane prevents visualization of its capillary structure
(E-'igure 3.47K] and its proximity lo the fovea, 'l'he sub-
retinal exudale that surrounds the neovascular membrane
3,4ft Natural course ot focal scars in the presumed
ocular histoplasmosis syndrome^
A —C : Ac-quisilLon o f a new local chtorLoretrnaE scar. Nole two
peripheral atftdf&hic Lh oru ida scars in л patienl with active
pulmonary disease and Bernorrhgjjjc delachmenl of lEie т и с -
ula (A). AngiojjjapEny showed no evidence ol other local cEro-
roidaE scars :E3 . Compart! with photograph ( O taken 7 years
taler. Nole increase in Ihe pijjmenLalion of old scary and
presents of an additional scar (arrow, C l in 1971.
Choroidal neovascularization and hemorrhagic
delachmenl of the macula occurring at the siies
of previously observed chorioretinal scars in the
presumed ocular histoplasmosis syndrome.
D -F: A pErifovBtl scar was piesenl in 1^Cv3 w hen Ihe visual
acuilv was 2(У15 (D and El. Three years Later the patienl
develtjfxid serous and hemorrhagic delachmont of lhe тплс-
ula (Hi.
G —I: A small perifoveal scar (arrow; G ) was harely visible
b irtiiicfq sn Jp ically in lhin paLLenL when he wan exam i mid in
January 1969. Visual acu ily was 20/20. Angiography showed
laint spoil) hyperfliMresoeJfic-e i arrow, H i. In |uly l rJ7 l he
developed serous and hemorrhagic dlscflorm detachment (1b;
his visual acuily was 20/60.
j-L: A 2 7-year-old wom an witEi visual acuity of 20/20 had
mild chorioretinal changes between 4 and 6 o 'clo ck at
Iho udj^e a t the oplic disc in Augusl \ 96S - ; J Angiography
showed evidence of juxlapapillary scn^rring hul no chorioreLi-
nal scarring fn Lhe m acula (l£). In Seplember 1969 sEie devel­
oped serous and hemorrhagic deLachmeril of the macula
secondary lo a choroidal neovasc uEat jntm brane ariiin^ a I
iho edge of the oplic disc IL :.
lA—L Irunn C iu .Li iJ Wilk:risi:n
stains Intensely TS'ich fluorescein. I Eie various hemorrhagic
and cicatricial disciform stages of macular detachment
show fluorescein angiographic features similar to lhal
described in patients with A M I). Angiographic evidence
of serous detachment ofthe RPE occurs very infrequently
in patients with POH5 unless they are 60 years of age or
older. E-luorescein diffuses from the choriocapillaris as well
as from the retrobulbar vessels lo stain lhe sclera and sub­
net inal tissue wilhin the focal and peripapillary atrophic
chorioretinal scars [I'igure 3.4SE} and Е;]Л1и-('-"1
Natural Course and Prognosis
Over a period of 17 years the fundoscopic changes in a
series of patients wilh ЕЮ ELS were studied and documented
by means of fundus photographic maps and fluorescein
angiography al the Bascom E\ilmer Hye Institute to deter­
mine the natural course of the macular lesions as well as
the widely scattered atrophic chorioretinal scars.-' ч’ :' u ыа
 Once macular detach ment has occurred, ihe visual
prognosis depends on several factors, 'lhe proximity of the
CNVM Lo the center of the fovea is the single most impor­
tant factor. Following retinal detachment the CNVM may
not grow or it may expand in a circular pattern or, less
often, in a tonguelike projection from the defect in Bruch's
membrane. Usually the membrane does not extend fur­
ther than I disc diameter from the Bruch's membrane
defect. :Vs long as the sub retinal CbJVM does not grow
beneath the fovea, the patient with either a serous or hem­
orrhagic macular detachment may regain good centra!
vision following retina! reattach ment, whether it occurs
spontaneously [Figures 3.47C-], 3.4УК and L, and 3.53)
or following photocoagulation treatment (Figure 3.49C-F
and G-l). In general, patients whose CNVM arises from a
point beyond 1 disc diameter from the center of the fovea
have a relatively good short- and long-term prognosis. I his
includes those patients who develop macular detachment
secondary to a sheet of sub retinal new vessels growing
temporally from the optic disc margins [figure 3.4SL).,■ ,"
Because recurrent detachment may occur and because it
may be associated with furLber growth of the neovaseu-
lar membrane, those patients with the origin of Lhe new-
vessel membrane within 1 disc diameter of the fovea have
a more guarded prognosis even if they recover successfully
from one episode of detachment. Some paLients, however,
may recover and retain excellent acuity for many years,
even in the presence of a CNVM extending beneath the
center of the fovea (Kigures 3.47h and 3.53].b5?,6Slt in some
cases this recovery occurs over a period of many months.
The frequency of recurrent detachment and duration of
detachment are also important factors in visual prognosis.
The fundoscopic and fluorescein angiographic finding of a
discrete zone of hyper fluorescence secondary to pigment
epithelial atrophy that extends from the site of the CNVM
into the central foveal area usually indicates permanent
damage to the overlying retina caused by a previously pro­
longed serous or hemorrhagic macular detachment.
!>rior to anti-VLGF therapy, multiple studies concern­
ing the natural course have found that patients with
r -
V -
4,44 Photocoagnlation treatment in the presumed
ocular histoplasmosis syndrome^
A —F: This 39-year-old palienl Was asymptomatic wtien seen
initially. There was o re inactive scar in (he m acula (arrow, Ar.
He relumed 5 years laler w ith blurred vision caused by a de
novo choroidal neovascular membrane '.arrtfws, tl and Dj. He
responded Lo afgon laser treatment ё and F I. Visual atuity ,il
the time o f F wns 20/20. Nolu I be changes thaL occurred in
the ju?;lapapillary scare duTinj; Lhe course of obserealion.
G - l: Ttiis 26-year-old man with a perifoveal reovascular
membrane ;arrows, C j and an adjacenl scar in the Tight eye
had лг^ог"! lase? ffeatment :Hl. ТЫтГу-ещЫ nnhnLhs alter treat­
ment, his visual acuity was 20/1 5 (I]. HLs visual acuiJy in Lhe
left eye improved spontaneously Erorn 20^200 ■ :К I Iо 2П/50 it:
duiiny Jhe period or" obsore'alion in Lhe righL eye1.
j- M : Ibis -tfl-yeai-old woman had received one session of
photodynamic therapy It) Ini-s subfoveal neova-scular mem­
brane 2 months before being seen. A pigrnenled nn^ o f choroi­
dal neovascularization located subfoveal I у with flecks of blood
was noted. №ripapillary atrophy typical ol presumed ocular
histoplasmosis syndrome was also present and her vision was
2CVB0 (J). A classic |)a(tem Ы lacv FluoresccncH was seen on
,i nj$i ogt.iphy iK). Thi1 membrane regressed and remained jnac-
Live afLw three monthly injections of bevacizumdb (L and Mi.
serous detachment and with choroidal neovascularization
that lies outside the capillary-free zone have a 60-70%
chance of retaining 20/40 or better vision in the affected
eyE.rt.w,-fi39-fiM: if iln? neovascular membrane extends inside
the capillaiy-free zone, 15% or fewer retained 20/40 or
better vision.
Follow-up studies have revealed that some of these
patients continue to develop new scars as well as changes
in the appearance and size of old scare (Figures 3.4SA
and G, and 3.4УА and |п a
few cases, small lesions may disappear. In the follow-up
study in Miami approximately 20% of patients showed
an increase In the size of one or more scars in the macu­
lar region, and over an average S. 4-year follow-up, 9 % of
patients with normal maculas by both biomicroscopy and
angiography developed new atrophic scare in the macular
legion.'
 Life-table analyses of the patients observed in № ф !
revealed lhat 12% w£tf develop symptoms in the sec­
ond eye within 5 years and 22% will develop symptoms
in Lbe second eye within 10 y e a ii 431 l'he relative risk of
developing symptoms in the second eye caused hy cho­
roidal neovascularization dev el oping in the jujilapapillary
area or macula is twice as greaL in patients with macular
scars compared to those with none. Ihe risk of developing
symptoms from a neovascular membrane arising in the
macula [excluding the juxlapapillary origin) is 5.5 limes as
great. E>aLienls with symptoms in their first eye should have
several early angiographic views made of the opposite eye
to exclude the presence of macular scars lhat may not be
visible biomicroscopically. O f 42 patients without biomi-
croscopic or angiographic evidence of a scar at Lhe time
of initial presentation, only two have developed macular
delachmenl from a de novo macular scar.
3.S0 Pseu dotumors caused by p re sume d ocuiar
hfstoplasmosis syndrome-
A and B: Large black peripheral hubretinal hemorrhage (A
that was initially misdiagnosed as a choroidal melanoma. It
was claused b y peripheral (boro idal neovascular membrane
Iarrows, Hi lhal becam e abparfflf! several monlh*; after pari m I
resolution of Lhe blood.
C - F : Ibis paLien-L w a s b e in g o b s e rve d Гот a ^ Is c ifO fm s^ap i.C :■
in lh e right e ye w h e n h e re lu m e d b e i i i J s t o f furl h e r d e cre a se
in v is io n . T h y disci fo rm le s io n h a d w i larg ed a n d W as associ­
ated w ilh s u b re tin a l e x u d a tio n . IL c o n tin u e d to e x p a n d o v e r
a 6 -m o m h p e rio d o f o b s e rv a tio n , a n d th e re ЩЫ c o n c e rn Lhal
а m e la n o m a h a d arisen in ltie scar l!> a n d Ё ). T h re *1 m o n th s
Eater [he lesion b e g a n to s h rin k s p o n ta n e o u s ly (F).
G - J : R ea ctivaLion oi a n e c c e n lric h y p e rtro p h ic s ta r [G 1 d is ­
c o v e re d o n a ro u tin e e y e e xa m in a Eio n in M a rc h 1 9Sfi in a
2 3 -y e a r-o ld w o m a n inom Tennessee w ith m u llifo c a f c h o rio ­
retinal scars in l>och eyes. Th e m u llip le w h ile spoLs in G are
artifacts. She w a s a s y m p to m a tic until M a rc h 1 4 ^ 2 w fie fi she
d e v e lo p e d loss o f central vis io n in Ihe right e y e . H e r visual
.n: Liii". h'r'.i:- j-: 11.11. 1. ' -1 иi. :iic n . u u Lir -1ечг and m ltIIiI jb u J.u ele-
valed <hnrioretififll lesion laiffil a rro w s , H a n d j) a n d m u lLifo -
cal c h o rio re tin a l scars -(arrowheads) superonasal lo [h e slig htly
sw o lle n o p tic d isc. It ie tissue c o m p ris in g the u p p e r right lo b e
(right large a rro w , 11 app ears to b e p osterior lo Ihe retinal p ie ­
m en! e p iltie liu m . F o llo w in g Ireatm onl w ilh cortico steroid s the
m a c u la r slar a n d retinal d e la t h m e n l s u rro u n d in g Lhe e le va te d
Ictsion re sD i.ytd . W h e n !аъ1 ж ' п in Se p Le m lxir 1 У У 4 Lheno w a s
a [ru llild ib u la te d elevated w h ite s ta r s u p e ro n a s a h y i|i. T h e
m a c u la a p p e a re d n o rm a l but h e r visual a c u ily w as 2 0 /2 0 0 .
К a n d L : НЧеи d o -c a p i 11nrv a n g io m a opLic d is c in a pa lien I
w iLh p re s u m e d O c u la r h isto p la sm o s is s y n d riim e .
Histo pathology
has been mnVincLtigSy defflo^trated
H is ic p liu r tiii a ip s u h t iim
histo pathologically in the human eye of patients wilh sys­
tem ic histoplasmosis on several occasions but in no patient
who at the lime df enucleation Was known lo haw lhe typi­
cal clinical picture of 679 The organisms
have been described in three eyes of palients with POJ iS,
but ihere is some doubl lhal lhe structures found were
П. &ipiuJ'fltmT.'£iW"6e3 I here is out' report of exogenous histo­
plasmosis endopbthdmilis developing in a palienl wilh lhe
vilreous wick syndrome after cataract extraction.1'75 Jn some
of lhe cases of histoplasmosis endophthalmilis the organ­
isms have been found in (he retina, lhe vitreous, and lhe
ciliary body, but no( lhe c h o r o i d . ;, :1 In a palienl with
acquired immunodeficiency syndrome [AII_>SJ who pre­
sented wilh mullifocal while retinal and subrelinal lesion^
the organisms were found in the reLina and oplic nerve
as well as lhe uveal iratiL479 i'igure 3.51 (A-С) depicts lhe
clinical and histopathologic findings of multiple choroi­
dal granulomas hi a 14-year-old boy who died of widely
disseminated histoplasmosis.^1 Ihis represents the early
granulomatous stage, which is rarely seen clinically, figure
3.!>1L> depicls a disciform macular detachment second­
ary lo a large solitary Hislopiasrrfa choroidal granuloma in
a healthy 18-year-old man ivhose eye was enucleated with
Lhe mistaken diagnosis of an intraocular neoplasm.:,J 676
H. organisms were found wilhin lhe granu­
loma.4'27гй3*-6'6 Examination of the opposite eye some years
Ealer revealed multiple atrophic chorioretinal scars typical
of РОЙ£.йМ 0 ne can only speculate as lo whether or nol
the patient had active granulomas in both eyes aL the time
of enucleation. Ihis patient probably was detected dur­
ing the infectious stage of the disease only by virtue of lhe
unusual size of the macular granuloma.
3.5 I H rsto p a thoEogiс fin d rngs in d i s s e m in a le d
s y s t e m ic h is t o p la s m o s is a n d in the p r e s u m e d o c u la r
h is t o p la s m o s is s y n d r o m e .
A —C : F u n d u s p a in tin g o f л 1 4 -y e a r-o ld b u y w ilh d is -
s e m in a le d s ysle m ic h isLoplaam osis u n d I w o fo c a l c h o r o i­
dal LnfilLraCes i A : . H is E o p a Jh o lo ^ jc e x a m in a tio n o f the E y e
o f Lhe p a tie n t illustrate d in A re v e a le d a fo c a l c h o ro id a l
H istoplasm a g r a n u lo m a (E3). N o t e d e s tru c tio n o f th e over-
lyitifl rc-liп л I p i gmexid e p il h e liu m a n d m in im a l e v id e n c e o f
in fliim m a lo ry bigns in th e s u rro u n d in g c h o r o id a n d r tf i пл.
S p e c ia l stains s h o w e d H istopiasm a capsuiatum (a rro w s , C k
D : La r^ e fo c a l c h o n o id a l jfra n u ltm v i s e c o n d a ry Lo h isto p la s ­
m osis in an [ й -ye a r-o ld b o y w h o s e eyfi was re m o v e d w i lh
Lhe mis la ken d ia g n o s is (if an in tra o c u la r tu m o r. Suit? IЬ л L
lh e ^ г л п Ы о т л h a d e ro d e d ih ro u g h ВгисЬ 'ь |Т№Пп Ы н П ё a n d
p ig m e n t e p ith e liu m into Ih e s u b re lin a l s p a t e . A rim o f p ig ­
m e n t-la d e n tfta c m p h a g e s su rro u n d s L h e ^ u b re tin a l р о й о п o f
Lhe jjrnfi u le m a I a n e w s I. fsfistoptasnia Cabsuldfum O T g a iib m s
w e re id e n tifie d w ilh in this le s io n . bears ty p ic a l o l lh e p re ­
s u m e d o c u la r hisLoplasm osis s y n d ro m e vvefre sur>bequenl iy
n o le d in the o p p o s iL e e y e .
£ : Serous a n d h e m o rrh a g ic d e la c h m e n l o l Ihe r e lira arising
fro m a n are a o f fo ca l n o n g ra n u lo m a to u s c h o ro id itis la rro w }
in a 3 2 -y e a r-o ld m a n . 1 lie e ye w a s A m o v e d b ecau se o f a
suspected in lra o c u fa r tu m o r. O p h th a lm o s c o p ic e x a m in a tio n
o! lh e o p p o s ite e y e re v e a le d lh e p re s e n c e oE scattered lesions
c o m p a tib le » i ) h Lhe H ^ ts u m e d o c u la r h isto p la sm o s is s yn ­
d ro m e . N o o rg a n is m s w e re id e n tifie d in I his le s io n .
F ,md G: ClinicopaLnolo^ic c:onelalion of focal alnophic cho­
rioretinal scar fn а 5Э-уелг-оЫ п'.ап with Lypical L'indin^y in
both eyes of the presumed ocular histoplasmosis syndrome.
N o t e Ehe lymphocyEic infiltration surrounding (h e area o f
d c u vn ^ ro w Lh of retinal -cells, presumaf]ly anliocyles, into the
u n d e rly in g c h o ro rd (C).
IA-C (mm К inlwurlh c.4л1.'" '|. Ё 1973, ArrtttiCJm W*dii .il Ai_4|l i.Hion.
A B n .iL ils г(■^■L-г,^^,:l. frcnTi G a i i ^ , i n J W .iu r n r jn L T ,in c l h!i,Mn Ё fro m
с Д ■
 I igure 3.51 [F and G) depicts the clinical and histo­
pathologic findings of an atrophic chorioretinal scar in
an eye obtained at autopsy from a patient who had been
treated with photocoagulation unsuccessful])' several years
previously for the typical fundus picture of PO H S^ ®
IJistopatho Logic examination of several of the atrophic
peripheral scars revealed focal lymphocytic infiltration sur­
rounding a nodule of retinal tissue (presumably astrocytic
proliferation} that had filled in a focal defect in the under­
lying choroid and P E’ti. 'Itiere was only minimal inflam­
matory reaction in the area of the large disciform macular
scars in both eyes [figure 3.52G and tl). Other authors
have also demonstrated similar choroidal lymphocytic
infiltrates around iuxtapapillary and peripheral atrophic
scars in these patients.c,flJ^iL' IMI<'
It istopathologic examination of eyes of patients with
POMS and actively growing C.NV.Vls demonstrates type
II subsensory retinal choroidal neovascularization. (See
discussion of types of choroidal neovascularization in
chapter 2.) New capillaries and fibrocytes. originating
within the choroid at (he site of a chorioretinal scar and
Lymphocytic infiltration, grow through a defect in Bruch's
membrane, choriocapillaris, and RPh into the subretinal
space [E'igures 2.11, 2.12. 3.46C, Er and h and 3.52A-C).
IJecause most of these patients are young or middle-aged
adults wilh the RPE firjnly adherent to ttrueb's membrane.,
the fibrovascuLar membrane overrides the RPH and grows
in a sheet Iike fashion in the subretinal space, ihe new ves­
sels induce reactive hyperplasia of the R PE at the site of the
membrane's entry into the subreLinal space and in front
of its advancing border during ihe symptomatic stage of
POEiS. ihe RPE cells align themselves in a monoEayer with
their base attached to the outer surface о Г the expanding
membrane. 'Ihese active new vessels are associated with
serous exudation or bleeding into the subretinal space. If
the proliferating RPE cells succeed in covering the anterior
surface of the membrane, exudation may cease and the
membrane may undergo involution (ligure 333]. E'igure
3.511 depicts a large subretinaL hematoma derived from
choroidal neovascularization occurring within an area of
Bruch's membrane and RPE destruction overlying a focal
nodule of lymphocytes and plasma cells in the choroid.
Ih e nodule contained no organisms. Pigment-laden mac­
rophages and proliferation of the RPE surrounded the
defect in LSruch's membrane and an inverted layer of pro-
LiferaLing RP£ cells extended along the outer surface of
the neovascular complex. Several focal areas of lympho­
cytic choroiditis and overlying relinal atrophic scars were
3.5^ Qinicopathologk correlations in the presumed
ocular histoplasmosis syndrome^
Л -C: Hypejpiijmtinted type И subnetinal neovascular meir-
Ljrane mislaken for choroiclaJ melanoma. Arrow fA and color
plate V -1i indicates origin o f rcew-vussel membrane at s-iLe of
□Id scar surrounded by a pigmented halo. H istopalEiologic
examination ol horizonlal section at the level o f focal scar
Ia now. A i shfltos psreDwth of" n ew vessels from the Cftotnid
(curved arrow, ti: inlo Lhe subrelinal spate. Note hyperpias-
tic retinal piemen I epi Ihelium :KI3E-: Istrai^hl nr rows) л I edtje
a t CiE>r<TVris-i. ular membrane, w hich is covered on its ante­
rior surface by Ihinned KFb (Open arrow i and on its poste­
rior surface by an inverted layer o f КИЕ. Horizontal section
ill lhe le w i o1 lh e optic disc shows lar^e subretinal fibrtjvai;-
cuLar membrane Iarrows, Cf lined on ib posterior surface by
a layer of inverted R P t. Note partial preservalion til" : elinal
receptors and tenuous adherence of the libruvascular rnem-
Е)гале 1o Lhe overlying reli na and underlying nalive: RPL.
D —F: Surgical excision ol a type II subloveal neovascular
memEtrane in I his 3 0-yea r-old Wom an who nuk'd lois of
cenlral vision caused E]y ingrowth of choroidal new vessels
at the site of a focal choriorelinal scar ■:[J.I. Ih e visual acu ­
ity was 2Qi&0_ The neovascular membrane was gmspud w ill:
forceps and d ra p e d ihrough a retinoLomy sile temporal lo
Lhe tfiacula i t '. Note normal KE’fc (arrowl in lh e Center of the
macuEa. Several weeks later the visual acuity has returned to
20/20. NoLe old chorioretinal scar Harrow I and sclerolomy
sea r lem рога Ily.
G and H : C linicopathologic correlation o f pigfnented dis­
ciform near in patient w ilh presumed ocular hislopJasmonis
syndrome (same patient illustrated in Figure 3.43F and GJ.
Histopathologic examination revealed a subretinal I’ibro-
vascular scar separated from Bruch's membrane and rem­
nants of the nalive HEhb Ilow er arrows I Lny an inverted layer
ot R PE (upper a nows), evidence suggesting type II choroidal
neovascu lari zation.
preseiiL in the peripheral fundus. 'Jhis eye was enucleaLed
because of the incorrect diagnosis of choroidal melanoma.
Ophthalmoscopic examination of the opposite eye at a
later dale revealed the presence of scattered focal atrophic
chorioretinal scars compatible with P O ]IS *76
Choroidal Lesions similar to those occurring in humans
have been produced experimentally in animals infected
wilh H. capssiiatum .^^1 Exacerbation of Lymphocyte
infiltration occurring in the vicinity of macular or juxia-
papillary scars occasionally may cause reactive vascular
and RPE hyperplasia and tumefaction simulating a choroi­
dal melanoma (E'igures 12.I4M-L, 3.50C-J, and .V^IA-CJ
or benign hamartomas (figures 3.50K and L and 12.14К
and G }.
Pathogenesis 3.S 3 С Iinicopaihol ogic со rrdat ion a f spo ntane on s
resolution of sub fovea! type El neovascularization
Kvidence supporting lhe coEtcept lhal tl. SfrpsuiaftjfWi is a associated with good visual acuity in a young woman
cause o f this, din Leal syndrome in the USA Includes ( I ) with presumed ocular hi slop las mos is syndrome L
50-91?% associated incidence with л positive histoplas-
A —E : A 2 7 -y e a r -o ld w o m a n n o te d loss o f central v is io n
min skin lest; (2 } the high incidence of demonstrable lym­
caused b y я ju x la fo v e a l su b retin a l n e o v a s c u la r m e m b r a n e
ph ocyte stimulation and transformation la hJitfopfesmin (a rro w , A l . T h e s u b re tin a l b lu o d a n d e x u d a te re s o lv e d s p o n -
antigens in Lhese palienls; [3] good correlation between lanEMJUs lv- уел г? Ы е г sht' had ,i retLiTrwnl serous a n ti
the prevalence of the disease in areas where histoplas­ heri^DTThsSiC q rta c h rriE rtt o f lh e left m a c и I л, ,m d a n g io g ra p h y
mosis is endemic and where it is not; (4) frequency of s h o w e d e v id e n c e oE s u b fu v e a l e x te fis le ti o f (he m e m b irin e iE3
radiographic findings of multiple pulmonary scars typi­ лги! С ) . H e r vis-ил! a c u ity w as 2(1/70 . The dete ch m unt c k a r e d
s p o n ta n e o u s ly a n d she re c o v e re d visual a c u ity o f 2 ( V 2 5 ,
cal of histoplasmosis; (5) the Walkersville epidemiologic
w h ic h she m a in ta in e d lor 9 years w h e n s h e d ie d b e c a u s e
study1"11; ( 6J (he identification of Ш$о$йнтщ organisms
ut m e ta s la tiE е л г и п о т л . H t ^ f e p i d [ ^ i c e li m i n a ti o n
in the eye of at least one patient who was subsequently re v e a le d л tlnn a tr o p h fc s u b fo tc ^ l fib ro v a s tu la r m e m b r a n e
observed Lo develop lhe typical POHS picture in the i л n o w s , D). T h e sepa ra tio n o i Ih e retina fro m the m e m b r a n e
opposite eye [figure 3 311>); (7) the finding of multifo­ is a n a rtifa c t. H i^ h e r -p o w e r v ie w o f Ih e m e m b r a n e (Ё) s h o w s
cal scars typical of pO HS in si к of eight patients who e n c irc le m e n t o f the m e m b r a n e b y a n a Ero p h lc layer o f retinal
had systemic histoplasmosis some years previously^; p ig m e n t e p ith E lE u m (.КРЕ) A r r o w h e a d s ) e x c e p t w h e r e iE c o m -
p .iu n ica te d w ith the c h o r o id . ЬпллИ arTcAvs indici^te n fllive
and (ti) the experimental product toil of PO llS, includ­
R .F E эерлrated Ira m o v e r ly in g in v e rte d K K E cells a tta c h e d (o
ing development of subretinal neovascularization., in sub­
lh e m e m b r a n e . La rg e a r r u w in d ic a te s scleruLic a n d o c c lu d e d
human primates following intracarolid infection of П. b lo o d vessel in Ih e m e m b r a n e . T h e r e w a s s o m e th in n in g o f
ttipbditi urn.f t 2 7 G42.6?i, iД4-юа the re c e p ld i c e ?II la y e r.
Although the pathagenesis of this disease is uncer­ F : th e d ia g ra m s u m m a r i z e Elio s e q u e n c e o f e ve n ts in this
tain, the following is postulated: during an acule primary p a tie n t.
pulmonary infection with H, aipsuhftum, these patients
develop dissemination of the organ isms in the blood
stream and multiple sinaU granulomas throughout the 3.52A-t!), supports the theory that allergic phenomena may
body including the choroid. Except for mild respiratory play an important role not only in gradual changes observed
symptoms, the patient is asymptomatic during this phase in the atrophic scare but also in stimulating choroidal neo­
of the disease. 'Ihe primary choroidal lesions are suffi­ vascularization and macular detachment, i he failure of mosl
ciently small thiit even when they occur near lhe central patients with early macular detachment to show an apparent
fovea I area, they rarely produce visual symptoms. Because response to intensive corticosteroid therapy is disconcerting
the human being is very resistдш to ihis organism, it if indeed allergic phenomena are important in the patho­
es rapidly destroyed, leaving minuLe atrophic scars sur­ genesis. By lhe time therapy is instituted, however, the pro­
rounded by hype rim mune tissue. It is probable lhat most liferative vascular changes may be sufficiently advanced that
of these focal scars are subclinical initially. Over a period suppression of the allergic reaction is insufficient lo stop or
of yeare recurrent lymphocytic infiltration around these slow the exudative and hemorrhagic complications.
foci produces a gradual enlargement of these scars so lhat Evidence supporting the concept lhat the macular
they become ophlhalmoscopicaliy visible. When they lesions are caused by vascular decompensation and/or an
occur in the macular region and adjacent to the optic disc allergic reaction at the site of a previous choroidal scar,
these scars represent a locus minoris resistentiae. where rather than the direct result of an infectious granuloma,
the choroidal circulation is exposed Lo the subretinal includes: ( I ) failure to find evidence of active histoplasmo­
space. Ну virtue of the hemodynamic stress associated wilh sis elsewhere in these patients; [2] failure to find ophthal­
the peculiar blood supply in the macula, these palietils moscopic evidence of active choroidal infiltrates elsewhere
are predisposed to the development of serous exudation., in the eye; (3) failure of the lesions lo respond lo antifun-
choroidal neovascularization, and serous hemorrhagic dis­ gal therapy0'^; (4) failure of the disease lo worsen when
ciform detachment. An exacerbation of the lymphocytic treated with corticosteroids; and 15} occurrence of serous
infiltration around these scars may be important in precip­ and hemorrhagic disciform detachment in the second eye
itating these complications. at the site of a choroidal scar that was usually present al
'ihe finding of focal lymphocytic choroiditis in the vicinity' (he time of delachmenl in the firsi eye. Jhe development of
of apparently inactive focal chorioretinal scare {I’igure 3.311-' macular detachment in some patients with POH5 during
and C), as well as in scars associated with an actively grow­ pregnancy, usually during the last trimester is further evi­
ing subretinal neovascular membrane (figures 3.3it and dence in support of vascular decompensation.
Рггаизгшге!1titu la r HistpplasiJiuai* ЬупЛтсчие \ 73

E^ly occur rsovasolaisslETi

5>nplbTalic &:age

Eariy ilage invulirnn

L v.-? stagE .ihor

Differential Diagnosis
The Lfpical picture of РОЗ IS has been reported in patients
from nonendemic areas of histoplasmosis and undoubt­
edly can be caused by other otguntanas, such as Cacadieide?
[Figures ]U.I7A-]: and 30.3 8A-С J :u0 l’he clinician must
rely heavily on lhe extramacular findings Lo differentiate
POMS front other diseases., such as panuveitis and mul­
tifocal choroiditis1,1 {see discussion of pseudo-POl IS,
p. 9SS)r diffuse unilateral subacule neuroretinilis (see p.
S64], vi Uliginous chorioretinitis (see p. 103a), and mul­
tiple scars caused by toxoplasmosis (see p. 84$).
Diagnosis
Jhe diagnosis of РОЗ LS is based on the clinicaE features.
Cutaneous reaction to НЩорИшгл antigen and serologic
tests, including com pi ement fixation, immunodiffusion, and
mycelial antigen identification, are limited to confmningthe
diagnosis in patients wilh unusual clinical presentations.
Treatment
Jhe medical treatment of РОЗ iS is unsatisfactory. Although
it is of some theoretical value, there is little evidence lo
date to support the practical value of oral and sub-Jenon's
injections of conicosteroids. L'heir use should be limited lo
those patients with a relatively recent history of loss of cen­
tral acuity whose lesion does not reveal the typical features
of a CMVM. Jn such cases the author uses 40-100 mg pred­
nisone per day for several weeks, and then on an л]ternate-
day basis for several weeks, [f no response is apparent, lhe
dose should be rapidly tapered and discontinued.. 3f appar­
ently favorable responses occur, then a longer schedule of
progressively decreasing dose may be used.
Photocoagulation has been advocated for the treatment
of the neovascular component of E’OJ IS (Figure 3.49C-3;.
C-])W?,J«.W5,roi-7fc 'ihe Macula Pholocoagulation Study
(MP5] has demonstrated Lhe effectiveness of intense laser
pholocoagulation of CNVMs in presenting severe Visual
Loss of six or пюге lines of visual acuity in the following
groups of patients with i’OJ !S: ( I ) intense argon laser pho­
tocoagulation used lo cover the entire area of CNVMs that
lie outside the capillary-free zone; ( 2) krypton laser of iux-
tafoveal CNVMs Lhal do not extend into the center of the
macula; and {3} krypton laser of persistent or recurrent
neovascularization following pholocoagulation (I'igure
lhe long-term results of photoco­
agulation of juxta foveal and extrafovea! neovascularization
in patients wilh POHS are good.'''1''" 1 '[he rate of persis­
tence and recurrence of CNVMs after photocoaguEalion in
the M I’S slLidy was 23°-i and respectively7^ Jiolb were
associated with an increased incidence of severe visual loss.
Surgical excision of type il subreliiinil neovascular mem­
branes that have extended beneath Lhe fovea has restored
excellent visual acuity in some patients wilh POEH5 (Figures
2. 11, 1.12. 3.52A-l:) 2&J-№!j--k'6:’:!i-7jn lhe best candidates
3.54 Idiopathic polypoidal choroidal vasculopaIhy -
recurrent large sub retinal hemorrhages.
A -F: !?>$ 50-yea r-ol (3 African Am erican w tim an was seen for
sudden Joss of vision in ht? riftht eye Lo tounl fingccs. A lar^e
m acular зиЬгеЬпл! hemorrhage noled and an antjiogram
showed moslly blacked fluorescence, except fur a small area
d E peilusian. Slit* reLumed 6 inonlhs laler with .4 vision of
20/400 in this eye and 2(1/200 Ln Lhe bellow eye. The suhweti-
naf blood was mosllv [jone, Ej u I a Abiotic рп-rtly conLracLed
p<]Ivp was seen in lh-е superior macula. 5ubrelinal lipid and
ch-oriorelinal vtarfold was also noted (O . She was poorly
complianL with her follow-up and returned 2 years Eater w ilh
ли improvement m lhe Ict'l eye vision L<] 2tV40. Two years
later she developed several pjllypS and subnormal blood in
Lhe inferior m acula il? and tj. Two more уеагъ 3aLer1he blood
arid lh e po3vps had disappeared and the vision was CV 502 1
in ihis eye and 20.40- in Lhe iefl eye 13-'.
G - l: This f) 5-year-old African Am erican wo.nwn w ilh hyper­
tension was known !o have bled in lhe lefl eye 15 yea гг pre­
viously and IohI vision. Her vision was 20/20- on the right
and 20-400 on the left. There w ere small oran^isb nodules
temporal Iо Lhe disc and several drusen superotemporally
ft!', rndocy^ninc едгеоп angiography confirmed Lhe polyps
I Hi; the left m acula had a disciform scar fl'i.
Laser treatmenL of polype
]-L: This 58-year-old man of African Am erican and
Caucasian heritage developed progressive fipid and shallow
subretinal fluid whiPe lhe polype w ere beiny observed (Jl.
Moderale-inlensiLy argon green laser lEong-duralton, low lo
intermediaLe power) was applied Lo the exlrafoveal polyps.
1hree monlhs Iа к т lhe fluid has resolved and the lipid exu­
dates have decreased ILJ.
for surgical excision are patients wilh recent subfoveal
extension of the membrane thal has arisen from an iden­
tifiable scar outside the capillary-free /one. Pholodynamic
therapy has also been successful In treating subfoveal mem-
bractes secondary Lo PO HS.'2i'7-- However, a safer and
more effective iherapv has been the introduction of anti-
VEiGh therapy, in the treatment of most cases of exlrafoveal.
juxtaftweal, and subfoveal membranes.1 •*' A monthly
treatmenL regimen of about four infections of hevacizumab
or ranihizumab is first performed JJepeat treatments are
necessary only tn some cases and can be performed as
needed. Surgical excision of a juxtapapillaiy membrane
may still be considered in an occasional patient.""
Patients with retention of useful central vision in one or
both eyes should be instructed Ln the frequent use of the
Amsler grid and near-vision card and the importance of
prompt examination if changes are delected.
Reactive Lesions Simulating Melanomas,
Hamartomas, and Papilledema
As mentioned previously large subretinal hematomas aris­
ing from subretinal neovascularization occurring wilhin
peripheral as well as centrally located chorioretinal scars
may simulate a choroidal melanoma. Additionally, reaclive
proliferation of subnetinal fibrovascular retinal gjial vascu-
Ear tiss-ut’. and retinal pigment epithelial cells may simulate
choroid;*] melanomas [Hgures 3.50Л—J, лn J 12.14H-E.);
choroid jJ hamartomas, e.g., cavernous hemangiomas
and osteomas [ligure 71,50<J—J); and retinal hamartomas,
e.g.. capillary angiomas (figure 3.50K}, astrocytoma, ,ind
combined retinal and pigment epithelial hamartoma (see
figures 3.50K I. and I2.1^1-'and g )/ J|i" j" ihe stimu­
lus for this exuberant reactive proliferation is presumed lo
be the same recurrent lymphocytic response (hat causes
enlargement of the focal chorioretinal scare in i’OJ S-5.
Rarely, the mass lesion may be caused by proliferation of
И ctificiitrdjrrr with ill the mass/'" As might be expected
from lhe frequency of jujilapapillary scars in POJ ЕУ, there
is some predilection for ihese reaclive tumors Lo develop in
that region. In addition lo lhe more slowly developing jux-
tapapillajy pseudo tumors-., patients with POEiS may present
wilh acute visual symptoms, usually a temporal scotoma
and optic disc swelling simulating papillitis, papilledema,
or neoplastic infiltration of lhe optic nerve head.6*y,'fi5lJ
Ihese latter patients must be differentiated from patients
wilh acute blind-spot enlargement associated wilh multi­
focal choroiditis and pan uveitis lhat may simulate PO BS.
[See discussion of pseudo-PGHS and acute zonal occult
outer relinopalhy in Chapter lb pp. 9SR and УSO.)
HISTOPLASMOSIS RETINITIS
AND CHOROIDITIS IN IMMUNE-
INCOMPETENT PATIENTS
Multifocal active while retinal Subretinal, and choroidal
Lesions may occur in one or both eyes of patients with AIDS
or other immune-incompetent slates (see Chapler Ш).
IDIOPATHIC POLYPOIDAL
CHOROIDAL VASCULOPATHY
(MULTIFOCAL IDIOPATHIC SUB^
RPE NEOVASCULARIZATION
OCCURRING IN DARKLY
PIGMENTED INDIVIDUALS,
POSTERIOR UVEAL BLEEDING
SYNDROME)
Although neovascularization occurs much less commonly
in black persons. Orientals, and darkly pigmented individu­
als, these patients, most of whom are black middle-aged
women; may develop multiple and recurrent serosanguine-
ous detachment of the pigment epilhelium and retina asso­
ciated with multifocal, often orange nodular or plaquelike
areas of'sub-PPL neovascularization, lhat early in lhe course
of the disorder are often mosl prominent in the iuxtapapil-
Eary region [figure 3 .55) ^-^a^io.si^.ftj-r ^\лпу 0f these
3. т. ii Exten sive id iopat hi с poiypo idal с bo ro idal
vasculopathy,
Д -Н : Л 70-venr-old CaiJ£asia|i worn .in was referred fnr
worsening blurred vision ir> bolti uyus fur 5 mornlm. Her
vision was J0/50 о гг lhe righJ and couni iinj^ors an lhe left.
Both eyes had several poLkets of rh in al piemen I epithelium
iHh’t j and areas of blood :A, C, D.
С Lind H. arrows}.. There w ere areas of Lhoriore!inal stars
лnd suhretmai liEircisis 1'iR F l mure in the rij^Hl 1hiin IcM eve
fG and H:. The left mat-ufa had suhrotin al fluid. Апц]Огцгат
s h o w ™ la p il fiiiin■j, t)f the RPE dm ac. limerits in bolh eyes ■E-l
and Fj and indotyanm e цгееп demonstrated polype IEI. Focal
taser was done bo I fie Rh’E detachment temporal to the fovea;
3 wueks Idler Klt viticm Jiad improved to 2CK^50 with resi.)-
lulion of 'SKF. Another monlh Liter she had irmv subretinal
blood around I his K PL dLlacbmenC. Inlravitroal b evaciiyrn ab
wan Iried with no si^nifrLanl roduition in £RF. ih e was sub-
sequenlly managed locally and no further informali«n wns
available.
sub-RPL angiomatous lesioEts show minimal evidence of
perfusion and late-staining fluorescein angiographicallv
(l-'igure 3.55} H 0" J2 in ihose who are subjecl to recurrent
episodes of symptomatic bleeding, there is a predilection for
development of vitreous hemorrhage, '['his disorder should
be considered in the middle-aged or older black woman pre­
senting wilh a dense vitreous hemorrhage. Since its original
description in pigmented individuals, the disorder has been
seen in all eLhnic races, including Caucasians (Rgure 3.54). It
is more common among Japanese and Orientals and makes
up a significant proprlion of their AMD palients.'33 5 lhe
polyps can be few and confined to lhe posterior pole, or they
are peripheral or extensive [t:igure 3.55).
They are visualized well on indocyanine green angiog­
raphy and can be located within lhe choriocapiHaris or
dieeper in the choroid (figures 3.54 and 3.55H}. When in
the deeper choroid or if the blood flow is slow within the
aneurysmal dilatation, they are not easily visualized on the
fluorescein angiogram. Other than the orange nodules, the
presence of several pigment epithelial detachments, espe­
cially if associated with small or large subrclinal hemor­
rhages. should prompt the diagnosis of Et’CV [l:igure 3.54).
'lhey can sometimes mimic central serous chorioretinopa­
thy and should be suspected in persistent or recurrent
]CSC.' :: ' 1' Recently, high-resolution OCT has been
able lo isolate the polyp if in the choriocapi Haris. In
eyes that present with vitreous hemorrhage, ultrasound
may be helpful in delecting the extensive irregularly ele­
vated sub-RPli fibrovascular plaques that may be present
in the macular and exlramacuEar areas of these palients.
Perkovich el al. found a high association of systemic hyper­
tension in this group of patients.'1" One patient with
biopsy-proven sarcoidosis became legally blind because of
progressive subretinal fibrosis in both eyes.
hiiofwthii' J’-'-lii'ii'Uiijl/iPi1 I7 1
 Treatment includes direct laser photocoagulalion of lhe
exlrafoveal and exlramacular polyps (I'igure 3.53J-I.J. Care
should be taken Lo use low-power and long-duralion green
laser to coagulate lhe polyp slowty and avoid bleeding.
Photodynamic therapy7has been more successful lhan an Li-
VEGF medications in shrinking the polyps located close lo
the foveal center. Large subretinal bleeds can be Watched,
as mosl resolve with no sequelae (Hgure 3.53D-H].
I Lislopathologic examination of one eye of a white..
Зй-year-old man followed for 6 years because of multiple
siles of idiopathic subretinal neovascularization hemor­
rhagic pigmenl epithelial and relinal detach men is revealed
extensive subretinal fibrovascular proliferation and lym-
phocylic and plasma celE infiltration of the choroid/ 51 A
nonsynonvmous variant J62V has recently been suggested
as a possible candidate for causal polymorphism leading
to It'Ctf in Japanese palienls. i-
U N U SU A L C AUSES
O F C H O R O ID A L
N E O V A S C U L A R IZ A T IO N
It is probable lhal any disease lhat damages lhe ftPE is
capable of causing choroidal neovascularization as a sec­
ondary response to the injury. Some unusual causes of
choroidal neovascularization that are discussed elsewhere
in this book are acute niullifocal posterior placoid pig­
ment epithet iopalhy [see p. 9St), rubella netinopal hy (see
p. 5 lS )f best's disease (sec p. 240), uveitis, demarcation
lines caused by rhegmalogenous retinal delachmenl (see
p. 6S 6). chorioretinal folds [see p. 220J.. pholocoagula-
Lion, oplic disc colobomas and pits [see pp. 1260-1262)f
chronic papilledema {see pp. 1294-12^6. fig. f 5.171}-11),
and hyaline bodies of the oplic nerve head (see p. 126Й].
A C U T E O C C L U S IO N O F THE
S H O R T C IL IA R Y A N D C H O R O ID A L
A R T E R IE S
We seldom have the opportunity to see palienls wilh
eilher functional or structural changes in the eye caused
by localised occlusion of the short ciliary or major choroi­
dal arteries because of the availability of many collateral
pathways of blood flow. Occasional ly, however, patients
present With visual loss caused by ciliary arterial obstruc­
tion resulting from prolonged elevation of lhe intraorbital
pressure (Hgure 3.56A-1- and !- t)i systemic vascular dis­
ease, for example, giant cell arteritis fl:igure 3.37)/4' " "lh
periarteritis nodosa,'1' malignant hypertension (I'igure
3.3tiG-]J, or sickle-cell disease'' ihrombolic infectious
arteritis such as that caused by phycomyoosis [mucor­
mycosis) '' and herpes zosler (see acule relinal necrosis.,
and figures 30.43 and 10.46J' '-" embolization S5-75i;
Outer retinal ischemic whitening and infarction
caused by transient occlusion о I Lhe choroidal
circulation.
A -F: O n e day aller pfiacoernufsifl^atkiri erf a caLaiai:t ihis
37-year-old mad nuk'd a lartje centra] sccloTTia in lh e oper­
ated eye. Mute £h& cenLral cbejiy-red spol :R' and poJvgonal
islands of outer retinal whitening (A and С) at Lhe function of
the diffusely ischem ic and nonischem ic retina. A 30-second
angiogfarn showed polygonal zones oe" slainrng o! the reti­
nal dijftnefil epithelium IRF’L'i and ouler retina (□>, Fourteen
inonLhs later visual acuily was. 20/25. l'h-ure was a dense.1
parateritral siotom a to finder r-bunting that corresponded
w ilh lhe areas o f K P t derangement (E and hi.
Inner and ouler retinal infarction caused by transient
occlusion of the choroidal and relinal circulation by an
intraorbital hemorrhage-
G —|: Ischem ic optic neunopalhy (H i, palchy areas af inner
nelinnl ischemic whitening in the macula, and wudjje-sbaped
a№as fif ischemfe whitening ot" lhe ouler relina [am^tiifheads,
G and H i caused hy ophthalmic artery obstruction in а
wom an w ilh severe hvfjerlension and 3theroscie№rtic cardio­
vascular disease. I^ole delnv in choroidal and relina] arterial
perfusion at 4Й seconds ■!> and late slain ing of ouler rhin al
ischemic areas (|l.
К and L: After general an-trelhesia for a rhinopiasly. Ihis
1^-year-old heaflhy wom an aw oke with pain, severe lid
swell mg, and blindness in ihe right eye caused hy obslnuc-
Ldcjn of Ihс choroidal and retinal c.irculation. A l Ihe lim e of
these photographs 5 weeks later her visual acuity in ih e right
ц-ve was no lij'hl perception. IN'ole optic atrophy, narrowing
of retinal blood vessels and se^menlal W ed g e& hip eo zones
ol severe mottling and alruphy of lhe K FE in the peripheral
fundus. Angiography di'monslraled 4jn increased relinal cir-
culalion lim e and diffuse KFJl chang^si
1
|Л - > m i n i h l c 'i i . 'i i t i j u m c l , i l . t .M id I- f r o m t l a u .m r l f t i r r b h . ■
and hyperthermia.' ' Occlusion of the posterior ciliary
arteries may occur as a complication of surgery involving
lhe posterior sclera such as the Vasco-Posada sectioning
of the scleral ring lo alleviate central relinal vein obstruc­
tion. : Although the posterior ciliary artery blood sup­
ply generally has a temporal-nasal distribution on eilher
side of lhe op lie disc, in some cases the territorial division
of the ciliary circulation may be horizon tally based.7vi
Hecause of lhe rich anastomosis of Lhe choroidal vascnla­
in re, the area of delayed choroidal perfusion demo nstra Led
by fluorescein angiography during (he acute phase of the
obstruction is much larger lhan (he area of while ouler
retlrtal ischemia seen ophthalmoscopically [figure . 56G- j
sonie cases this choroidal hypoperfusion
may be associated with no visible changes in lhe fundus,
lhe rich anaslomolic nelwork in lhe choroid explains Why
multifocal gray-white ischemic lesions affecting Lhe pig­
ment epithelium and ouler retina caused by ciliary artery
obstruction rarely occur clinically.'^
 A Inline y. one of delayed choroidal perfusion may be
seen adjacent lo an area о Г krypton [лиг closure о Г one
or more large choroidal arteries in the absence of any evi­
dence of ischemic whitening of lhe outer retina hr perma­
nent damage Lo the retinal function in thaL area.'^''^"1
A triangular zone of solitary or multiple patches of outer
retina] ischemic whitening followed by chorioretinal atro­
phy is more likely to occur after occlusion of a large cho­
roidal artery in the midperipheiy of Lhe fundus, where
Lbere are fewer arterial anastomoses [Figure 3.56G-1.) (see
Chapter 6, and Figure У. l5A-F ).'l'‘:-7r'1
A peculiar picture of acute outer retinal ischemic infarc­
tion of the posterior retina may occur in patients complain­
ing of acute visual loss usually on the first postoperative
day following phakoemulsification for cataract removal
vitrectomy procedures, or neurosurgery procedures in
which prolonged pressure has been inadvertently placed
on Lhe eye (Figure 3.56A-C). -n Fundoscopic
examination reveals a picture (hat in ay be mistakenly diag­
nosed as a centra! retinal arteiy occlusion. 1Ъе outer rather
Lban the inner retinal layers are whitened. Ifie wintering
extends beyond the macula but does not reach the equa­
tor (Figure 3.56A-C). Multiple discrete patches of whiten­
ing separate Lhe diffuse areas of whitening posteriorly from
the relatively normal-appearing anterior half of the retina.
A cherry-red spot is present. Fluorescein angiography may
show no abnormalities of the retinal or choroidal circula­
tion times, or it may shotv a Late hexagonal or pentagonal
pattern of fluorescein staining in die area of retinal whit­
ening (Figure 3.56D). Mottled salt-and-pepper changes in
Lhe RPfc become apparent as the retinal whitening clears
(Figure 3.561: and Г"). The RPE in the fovea!a may remain
normal, lhe patients may regain a small central isEand of
vision and excellent visual acuity in addition Lo retaining
a broad /one of their peripheral visual field. Although the
pathogenesis of ihese changes is not certain, it has been
hypothesized (hat they result tiom an extended period of
elevation of the intraocular pressure just before or during
the course of surgery. ЧЪе duration of the pressure eleva-
Lion and closure of the choroidal and retinal circulation is
sufficient Lo cause ischemic infarction of the outer retina
hut not the inner retina. Jlie outer retina, particularly in
the posterior pole where it is thickest, is more sensitive lo
oxygen deprivation than is the inner retina and is more
predisposed to infarction during an extended period of
\,37 Chorioretinal and optic nerve ischemia caused
by giant cell arteritis occluding the major branches of
the ophthalmic artery.
A—D: Ischemic o plic neuropathy, cotton-wool palcbes in the
distribution o f cilioretinal arteries, and ischem ic choroidopa-
Ihy in a 73-year-old wom an w ilh acule loss a f vision in bolli
eyes (A . Angiography reveals deE&y in fjerlusion of lhe cho­
roid fE3 and О and I ale Gaining in Lhe inner retina and at the
level o f I lie relinal pit^nenl epil helium in Lhe papi Horn aculaf
bundle and m acular areas iD ). A Lem рати I artery biopsy was
positive for lemporal arLori Iis.
E nnd F: LSilaleral ischemic oplic neuropathy, choroidopathy,
and retinopathy in a 73-yeaT-oh; man With malaise, weight
lass, jaw claudicalion, and total loss ol vision in both eyes.
Two weeks pritw Lo the Etmdus photographs :E and Fj, he
develojied sudden Lola I loss of vision in lhe ri^lil eye and the
following dav becam e blind in lhe left eye. К ole the sevefe
oplic disc ischemia and sludging o f plood in the retinal ves­
sels o f the right eye (Ё) and lhe persistent cheny-iod spot in
Lhe left eye If >.
Disseminated intra vascular coagulopathy causing
submacular choroidal hemorrhage.
G —|: This 27-year-old wom an with anorexia, abdom i­
nal pain, arlhral^ia, fever, diarrhea, and bizarre neurologic
symptoms noled visual lost associated with yellowish jjTay
plaques and hem onhage in (he posterior choroid of both
eyes lairows, C|. ih e developed progressive ihrombocylo-
penia, hypofibrinogenemia, and accelerated fibrinolysis and
dierl. Hinlopalhokjrjjic exam ination o f Ibe eyes revealed cho­
roidal thickening farrowsr H) caused by intrachoroidal hem­
orrhage involving the temporal half of the macula. I Ькте was
extensive thrombotic occlusion o f the choriocapi I laris nid
larger choroidal arteries farrows ! and |l.
I t i - - I 1ГТУ1Г1 S jffn p J p i .Lnd Eu(dtlJWT.' '
closure of both the choroidal and retinal circulation. The
retina iti the foveoEar area, by virtue of its thinness, is less
susceptible to transient oxygen deprivation, '['his hypoth­
esis has been tested and verified experimentally in owl
monkeys. 1(1 [f (he retinal and choroidal circulation are
obstructed long enough, total irreversible blindness of the
eye and a biomicroscopic picture of widespread profound
ischcmic whitening of both the inner and outer retinal lay­
ers and ischemic swelling of the optic disc occur. This pic­
ture of combined ciHoretinal arterial occlusion ts followed
by optic atrophy and severe atrophic changes in the retina
and l£PE (Figures 3.SGG-L).
 Ischemic relinopalhy caused by ciliary artery obstruction,
unlike that caused by choriocapillaris occlusion (see discus­
sion in lhe nest section), is rarely associated ^\rLth exudative
re linn I detachment Induction of the perfusion pressure
in the /one o f ischemic necrosis of the IIPH and the resis­
tance of choroidal as well as relinal capillary endothelium
to hypoxic damage are probably important factors in this
regard. Experimental evidence suggests lhal the relink may
be resistant to permanent ischemic dam-age wilh occlusion
of the central retinal artery lasting for as long as 1 hour.
(See discussion of retinal artery occlusionr Chapter 6.)
Another mechanism of visual loss caused by iransienL
obstruction of the short ciliary arteries is thal of ischemic
optic neurapalhy related to hypoperfusion of lhe optic
nerve in the region of iheoplie canal (figure J.37A-F). (See
discussion of ischemic opLic neuropathy in Chapter 15.]
Color Doppler imaging has provided us with a new and
useful means of assess ing orbital blood flow."4'
ACUTE OCCLUSION OF THE
PRECAPILLARY ARTERIOLES AND
CHORIOCAPILLARIS______________
lh e rapid occlusion of segments of the precapiilary arte­
rioles and choriocapillaris by fibrin platelet thrombi may
cause acute necrosis of the overlying RPE and serous and
hemorrhagic detachment of the relina (Figure 3.5 7G-
J]7 SI-?S7 'Ihis pathologic change, referred to as fibri­
noid necrosis, is lhe resull of damage to lhe vascular wall
caused by severe spastic arteriolar narrowing associated
with severe hypertension [see Chapter 6] or collagen vas­
cular diseases (see Chapter ] ] ) or by D1C.
DISSEMINATED INTRAVASCULAR
COAGULOPATHY__________________
In DIC procoagulanls from various sources activate the
intrinsic and extrinsic blood-ctolling mechanism, lead­
ing to fibrin form alion and widespread occlusion of small
blood vessels. Depletion of clotting factors caused by con­
tinuous utilization of platelets and various coagulation
proteins .and activation of fibrinolytic enzyme systems
result in bleeding, shock, and widespread intravascular
clotting in the kidneys, liver, lungs, central nervous system,
gastrointestinal tract, and uveal tract. A variety of diseases
З .718 Hypertensive choroidopathy.
A: TFnift. paliunl had bi]<tleral ex u d aliw retinal detach г л у п I
ciL s 6 d by hypertension and severe renal disease. He died
boon after Ibis photograph, and his W e S oblainw l al
autopsy Istfe E).
B - D : Кои mi I pigment epithelium (KPLf degeneration and
dum ping (Elschnig spots; airuw) in a palienl w ilh chronic
severe hypertension and renal disease (E and C). Angiograms
showed evid en ce or Ihrombosed barge choroidal blood Ves­
sels A rrow s, D).
£: Hislopalholo^ic exam inalion or" lhe eye depicted in A
revealed esudalive retinal detachment and m uhiple focal
,1r-‘-.1- ii" xiin'm i: nlлч Iio: 1 cl Ihг1 КГ1 o v ltK :с■
■.11 ,rc,i-
□I fibrin pFalelet (jcd usio n I fibrinoid necrosisf involving a
choroidal arleriolc and adjacent i^norldtiiplllaris (b i t d w .
F—H: This 43-уеаг-uld womfln w ilh л hislory o f severe hyper­
Ions ion show? eifidei^fce of alherum,ilous pU que lom ialion in
the superior temporal r-elirral artery moderate optic atiophy,
and subtly S fc h n ifl spots (ai^tnv^ lhal are best seen angio-
graphically. N o le delay in choruJd^J perfusion.
may stimulate the intravascular clotting mechanism by
releasing thromboplastin inlo the circulation. 'Itiese
include malignant hypertension, severe toxemia of preg­
nancy, :"4 1 abruptio placentae,' 10 cancer (especially leu­
kemia). oi^an transplantation (especially renal yraft),'''' 1 'N
burns, bacterial septicemia, antigen-antibody reactions,
drug reactions, collagen vascular diseases,'1"'" ''1 ' 1 lym­
phoid granulomatosis/"^ Wegener's granulomatosis."1'1
Good pasture’s syndrome.14'1 thrombocytopenic purpura.'"-1,1'
thrombotic thrombocytopenic purpura/’00"1* '1 and famil­
ial dysplasminogenemia.'4 '1 lhe predilection for ihrombi
to develop in the choroidal but not the retinal circulation
may be caused by (he rapid deceleration of blood flow as
the blood empties from the choroidal arteries into the large
sinusoidal network of the choriocapillaris. ' " Retinal vascu­
lar occlusion occasionally occurs in patients with DEC but
in most cases is caused by factors olher Lhan intravascular
thrombosis.'1’''1 After treatment for systemic hypertension
and DlCi lhe retinal detachment resolves and patchy areas
of atrophy of the ]? [3L and pigment dumps (Htschnig spots)
that often are most prominent in the peripapillary and
macular areas remain as permanent scars."■'4' ' fclschnig
spots may be difficult to differentiate from inultifocal
lesions occurring bilaterally in some patients wilh fun­
dus pulverulentus paltern dystrophy, or following chronic
recurrent I CISC.
Malignant Hypertension
Patients with malignant hypertension may develop sec­
ondary detachment of Lhe reLina caused by acute mul­
tifocal areas of fibrin platelet occlusion and necrosis of
choroidal arLeries and choriocapillaris, and necrosis of lhe
overlying RPL [Figures 3.5& and 6.2<b to 6.2S)/I!;
Llschnig spots, irregular areas of pigment epithelial atro-
phy^ and angiographic evidence of choroidal vascular
obstruction often remain after resolution of the detach­
ment (Figures 3.5BC- 1>, and li.. and 6.28).’-*| Гt!’''!l1
3.?lJ Fundus changes caused by toxemia of pregnancy.
A: Missive* pnerd i nil I hemorrhage and retinal Hetachment in
a y H jr a irtfimafi who died several days later of com plications
q l eclampsia.
В and С: Th is 42-year-old H aitian wom an was hospitalized
because a t hypertension and generalazed seizures during Lhe
3j)lb week o f gestaticisi Three days afLer dclivery L>y cesar-
вап section she developed loss of vision caused by bilateral
bullous retinal detachment. K a le Lhe palchy white areas of
ischemic infarction of ibtf relinal pigmenl c-ffji Ihe.1! iLim LFit’ L:
ia nows I beneath Ihe retinal dcrfacbment <B). Angngraltls
showed m ulfiple art*as of leakage aL the level of Lhe KF’b 1C..
D and E: Acute bilateral loss o f vision occurred in a 29-year-
old moLhor soon after delivery of her baby. She bud severe
Lo\emia of pregnancy. ]"hrec: days a her delivery I here were
multiple w hile lesions aL lh e level of the pigment epi Ihelium
Find onEy minimal evidence of retinal delachm enl Early
angiograms showed a reticular pattern of non fluorescence
it.. M u lli focal areas o f staffing I arrow.1w-ere evidenl laler.
F and C : Thi-s feym ptoniatif t>3 -year-old wom an was referred
because of suspected heredomacular dystrophy. Visual acu ­
ity was 2tV20. The multiple Elschnig spots LarrowsJ and
branched pa Hern of yellow changes in bolh eyes were
caused many years previous^ by severe tosemia lhat caused
transient bilateral loss ol vision fust before birth of her sec­
ond child.
H and I: AsymplomaLic 50-year-old wom an wiLh KF3l
l hanges that were misinterpreted as henedomacular dyt-
Lrophy. She had experienced bilateral Visual Josh associated
wiLh toxemia of pregnancy just before delivery of each o f her
last Iw o children.
J- L Al age I S years ihis .^3-year-old wom an had eclam p­
sia and was blind in bolb eyes after delivery. She regained
2Q/4D0 visuaF acuity in both eyes. Note Elschnig spots
(arrows, J and L)r reticular network of pigment epithelial atro­
phy. narrowing of Lhe retinal arLeries, and peripheral inLra-
relinal m itral ion of pigmenl simulating a severe tapetorelinal
dysLrop-hy.
(A—
t Iroin C jSu and I 1ill Il'i ■' '
TOXEMIA OF PREGNANCY
A p p W tltp td y \-2°-b of palients who develop severe
hyperLension. proteinuria, and edema during lhe third
trimester of pregnancy- develop loss of vision caused by
serous relinal detachment (figure 3.59Л and II). d-7!W'?aj-
e: ' IhL& usually occurs ju-sL before or immediately
following delivery. A branching pattern of yellow-white
patches caused by focal necrosis of the К PE and outer
retina may or jnay not be evident [figure 3.5У t5 and D).
]Ъе detachment may be confined to the macula or, par­
ticularly in palients with seizures (eclampsia), may involve
the entire fundus and may rarely be associated with
bleeding into the choroid, subreLinal space, and vftre-
ous (Figure 3.59А]. These palients iqay or may not show
evidence of colton-wool patches and hemorrhages in lhe
retina. Angiography may demonstrate evidence of delayed
perfusion of segments of the choroid as well as mulliple
pinpoint areas of leakage of dye through lhe RPE in lhe
region of the subretinal yellow-xvhile patches (Figure
339C and L). After delivery and treatment of the hyper­
tension, the detachment rapidly resolves and recovery
of visual function is relatively complete in most patients.
An irregular branching pattern of hyperpigmenled dols
(flschnig spots), yellowish patches, and interconnecting
Lines of depigmenlation of lhe RPH often remains in lhe
juxtapapillary and macular area (figure H. and |).
ihese changes, caused by infarction of the RPE, are fre­
quently symmetric in both eyes and., if initially detected
on a routine eye examination years later may be incor­
rectly interpreted as signs of a macular dystrophy.
Ihey are often more evident angiographically lhan oph-
tbalmoscopically (Figure 3.ЗУ 1L^ G, I, and I.}. Patients
wilh severe toxemia тл у develop profound visual loss
and blindness secondary to total serous and hemorrhagic
retinal detachment and be left following recovery with
3 .60H EL L P sy nd ro me ( h em oEysis, elevated 1iver
enzymes, low platelets, and upper abdominal pain),
A-E Thifi 2 S -уен r-ol d O u c a s ia n wom an w«s diagntfse'j v/ilh
H L L L P (efevalEid Iiver enzymus anti low nlajSplets) syndnjm e
at 17 weeks' gestation and Llnderwejtt emergefjey с т я т п
нес I ion. SIte.1 rt!t|uired temporary hemodialysis for renal Fail­
ure Lhat №cove$fid- O n 4ht!- first day postpartum shy noted
M uned vision in her rij^hl pye. СХрЬфй \Iri.ftjogy co n stilEa li^
was ntiL m taih ed . Wh-un examined 2 mcmlhs I.Uer her vision
had improved Cotiwderably In 20/25 in each eye, Thu retina
W iiii attached vi'iJh interlacing mibnilinal fibrin plaques that
had Stallooed tA and 311. O ptica] СоИрёгТёПСЙ tomog­
raphy shows lhe mjitt?ri л I to be in [he subreUnal space. W e
presume she :i,ad Ssjjtensive enudnliw retinal detach т и п I
when symptomatic, that h ire? resolved leaving the protein-
aceotis material subr-etinally. Three weeks (D j and i months
(EJ later Lhe subretinal fibrin has decreased and resolved
alm a# completely.
iCautTny l^r D*vid Wfeliihcrji.)
extensive degenerative changes in the RPE and retina lhal
may simulate a diffuse lapetorelinal dystrophy (Figure
3.3yj—I.).-■' Correct diagnosis is important since lhe
changes caused by toxemia are notiprogressive.
The cause of toxemia of pregnancy is unknown. Some
pa lien Is presenting with bilateral retinal detachment may
manifest other evidence of DIC. for example, hemolysis.,
elevated liver enzymes, low platelets, and upper abdomi­
nal pain MlEI.LP syndrome). Some of these palients may
have normal or near-normal blood pressure.""’2'1 H E tiP
syndrome has been associated with centra! retinal w in
occlusion, serous and serosanguineous retinal delachmenl
(figure 3.ft0), vitreous hemorrhage. Purtscher-like retinop­
athy and occipital infarcts.:i-'-' Increased VLCF levels
have been noled in the serum of these women / "
Cottagen Vascular Disease
Palients With disseminated lupus erythematosus, ,3,SfflJ
poLyarierltib. ясойейа,801-^ disseminated scleroderma, der-
tnatomyositis, and relapsing polychondritis may develop
serous delachmenl of the macula с aused by fibrinoid
necrosis of the choroidal vessels (see figure 2.14). Ihey
may or may nal show ophthalmoscopic evidence of reti­
nal vascular involvement. 'Ihey may or may not have sys­
temic hypertension.
Goodpasture's Syndrome
Goodpasture's syndrome is characterized by lhe onset of
signs and symptoms of hemorrhagic pulmonary disease
(hemoptysis) and rapidly progressive glomerulonephritis
(hematuria) leading to progressive pulmonary and renal
failure. Deposition of immunoglobulin С occurs in a lin ­
ear pattern in the basement membranes of the glomeruli,
the lungs, and the choroidal blood vessels ,:|4 Circulating
basement membrane antibodies are frequently dem­
onstrated. Jhe autoantibodies are directed against the
Goodpasture antigen, which is part of the noncollagenous
domain of the alpha 3(TV) collagen chain. Approximately
75% of patients die within the first year. Scattered retinal
hemorrhages and exudates occur in approximately 10%
of the patients; bilateral juxlapapilh'.Ty subretinal neovas­
cularization and peripheral retinoschisis have been seen
in one patient.^1 * Kutlous retinal detachment second ary
Lo fibrinoid necrosis of the choriocapillaris and overlying
RPE may occur.SS? K
Systemic Necrotizing Vasculitis
(Wegener's Granulomatosis and
Lymphoid Granulomatosis)
Visual loss associated with multiple outer white lesions
at the level of (he KPli similar to lhal occurring in acute
posterior multifocal placoid pigment epilheliopathy in
palients wilh Wegener's granulomatosis'1’'10 and lymphoid
3.6 E Orga n-tr an spla nt с ho rio re linopalhy and
exudative retinal detachment
A-C: Ffvc months afLer a renal Jransplant, this 51-year-
old man noted bl:Eafera[ paracentral scotomas nnd bu rred
vision. After irafcarecl extraction hib visual acuity returned
lo 2 0/ 2 U Eh laterally,. t?uI his paracentral scolomas persisted.
Тчеле w pr6 zones af yellow Kb flecks and relinal piemen I
nhpfIhelium Rl-'E. i disTuplion pa ratxm Iral ly in fjoLh eyes (A .
A ngiography revealed w ilh in these zones n leopafd-sp^il pat­
tern СЙ n.onfluor£!sc:en1 flecks on- а background of hyperfluo-
rescen celC And □}.
t)- F : y e a n Sifter a hearl tmnsplanl Ihis fifl-vear-old man
devielofH-'d blurred vision And distortion o f vision in the ri^lil
eye associated with serous retinal detachment and progres­
sively enlarging zones dE RPE damage in a pattern similar to
lhe patienl in A -С. At the lime ol the photographs in D-F.
his visual acuity had irnpjrcjvt.4J hponLa nrous lv from 3;0/6l) lo
20/-50 and mtjsl of lhe subretinal !iuid had resolv&d. The Ы е-
phase angiograms showed pinpoint leakage p f EEuorescein
(anow r f ). The lefl eye was unal'tecled.
G - L : Two years afler a heart-tung transplant,, this 47-year-old
man noled mild visual disturbance. Examination at thaL time
revealed zones o f paracentral disruption and du m pin g of the
RF’fc associated w ilh localized serous retinal detachmenl ii:
the m acula o f holh eyes fG and Hi. Angiography showed a
leopard-spol pattern af i l u i ^ c e k e and pinpoinl areas of
focal staining in- bolh eyes. Fourteen monlhs later I here was
evid+jnt:e fitf progression of lhe pigment opilheliopathy .and
inferior bullous relinal deLachmt'nl Lhal exLended inlo Lhe
m acular areas. There was a widespread pa Hern of vellu w
fleckh resembling fundus flavimaculatus throughout the роь-
lerior l undi 11—L I.
. 7ч"
|A, C.!. .inrl Ci-L frurn GUi E t a l . I IW 2, Агiil -гi ■11 МСп1ч,lI
■ ■(X :■ !I I'll ЛИ r.i^h^ rt.icrved J
granulomatosis6* 3is seen occasionally. Retinal and choroi­
dal artery occlusions, serous retinal detachments, branch
and central relinal vein occlusions, severe retinitis and uve­
itis, sderitis, and sclerochorotdal granuloma, mimicking a
choroidal tumor are other posterior-segment manifesta­
tions in ihese patients.14:1 l:'
O R G A N T R A N S P L A N T A T IO N A N D
H E M O D IA L Y S IS
Patients following renal, heart, and heart-lung transplati-
Lalion may develop loss of vision caused by serous relinal
delachmenl associated with geographic zones of leopard-
spot pattern of dumping of orange RL’h and RPK depig-
menlalion in the posterior fundi of both eyes (Figure
3.G1J. rluorescein angiography accentuates these RPli
changes and during lhe exudative phases of lhe disease
demonstrates multiple pinpoint areas of fluorescein leak­
age within the zones of pigment epithelial damage (Tigure
3.61 R, C, Li, H I, and L). lhe subrelinal fluid usually
resolves spontaneously within several weeks or months.
Recurrences are common, 'l'he epEsodes of exudative
delachmenl do not coincide necessarily wilh clinical evi­
dence of graft rejection. All of the patients were receiving
a combination of oral corticosteroids, cyclosporine, and
azalhioprine. Any one or a combination of these drugs,
particularly the corticosteroids, may be of pathogenetic
importance.’^ ЧЪе pattern of pigment epithelial changes
suggests that acute damage lo the RHi, perhaps by local­
ized intravascular coagulopathy affecting the choriocapil-
Earis, may be responsible.
Multifocal serofibrinous retinal pigment epithelial
detachments and relinal detachment identical lo that
seen in patients wilh severe ICSC may occurr usually
bilaterally in patients receiving hemodialysis because of
renal failure^'' and occasionally after renal iransplanta-
Lion.46.07.м.7«.на ( Se£ previous discussion, ICSC, pp.
S4-86.) When occurring after renal transplantation, the
ocular symptoms have developed soon after the transplant
in patients who presumably were receiving hemodialysis
preoperativeiy. All but one of these palienls who devel­
oped ocular symptoms while receiving hemodialysis and
all of (hose who became symptomatic after renal trans­
plantation were receiving systemic corticosteroids, which
may either aggravate or cause ЕСЬС.4*"" Reduction of the
dosage of corticosteroids and laser treatment of exlrafoveal
RPli detachments may be beneficial in causing resolution
of retinal detachtffyail/'6 l.ow-fluence photodynamic ther­
apy is useful in eyes with widespread leakage.
E X T R IN S IC A N D IN T R IN S IC
E M B O L IC O B S T R U C T IO N O F T H E
C H O R IO C A P IL L A R IS
Kecause of the availability of multiple pathways of
coE lateral blood flow, embolic obstruction of the
3.bll Dys prote in e mia and serous macn Ear detach men t.
A—D: A 63-year-old man w ilh Waldenstrom's- macnoglobu-
linemia developed loss of central vision bilaterally associ­
ated w ilh localized serous retinal detachment (arrows, Bj in
lhe macula of both eyes. Ih e re w ere scattered relinal hem­
orrhages in Ifie periphery Ai bul minim al evidence of reLi-
naL venous; dilation. The visual acuiLy was 7/200 bilaterally.
A ngiograplifv revealed some scalLereri foci of mild relinal
m icrovascular changes, but no evid en ce of staining either
Ln Lhe relina or aL ihe level of the retinal pigment epithe­
lium (C Lind О]. Orre week later, following plasmapheresis,
lhe serous m acular detach m en t had nesoked anrl Lhe visual
acuity had improved Lo 2(^.2 00.
E-E: This wom an w ilh diabeLeb mellilub and m ulliple
myeloma developed loss of central vision caused by serous
relinal delachm enl in the macula :arrows, t) of botii eyes,
ih e hatl m inim al background di a belie retinopathy. The
deLnchmenl persisted and was associated w ilh an increase in
i. I-.■■Ii-■!к I l :ii■:>
| :' !"iv iF .i!l : i\ ■
. Angjogr.ijjh^ ч -.c.ih d —.
dence of background retinopathy and inlense staining o f Lhe
subretinal fluid.
choriocapillaris, whether caused by a shower of exoge­
nous embolic т а Leri aE, such as corticosteroid p reparat Lons
after periorbital injections, or fibrin platelet or cholesterol
emboli from (he carotid artery, rarely causes symptomatic
damage to the retina.' 56 fixpert men tally, it is difficult to
produce retinal damage and retinal detachment by embo­
lization of the choroidal vasculature alone. Injection of
emboli retrograde via the vortex veins to obtain an ele­
ment of venous obstruction, and photocoagulaLion lo
damage the RI41 physically as well as occlude the choroi­
dal blood vessels are techniques used to produce exudative
retina] detachment expert mental Еу.м"
Serous macular detachment may be produced ejtperi-
menLally in cats by photodynamic injury produced
by laser activation of intravascular rose Bengal.'’
HislopalboEogically the detachment is associated with
occlusion of the choriocapillaris and retinal vessels.
D Y S P R O T E IN E M IA C A U S IN G
S E R O U S M A C U LA R D ETAC H M EN T
A N D R E T IN O P A T H Y
Л palienl wilh Waldenstrom's macroglobulinemia devel­
oped bilateral loss of ct’Jilral vision caused by serous
detachmenl of lhe relina in lhe rrtaailar area, un associ­
ated wilh any fluorescein angiographic evidence of perme­
ability alien Lion of either lhe inner or ouler blood-relinal
barrier (Figure Л.62А-Е>]. One week after plasmapheresis
the relina fe attached bi Iale rally. Presumably ihe high lev­
els of abnormal serum proteins in these patients jnay gain
entrance into the subrelinal space and cause lhe accumula­
tion of water by osmosis. As demonstrated in lhe firsl case,
this may occur in lhe absence of a demonstrable alteration
of either lhe RFE or retinal vascular endothelium to fluo­
rescein (figure 3.6JA-D). Similar serous retinal detach­
ments that do nol exhibit fluorescein leakage have also
been seen in palients wilh multiple myelomar POEM S
syndrome (see below), and benign monoclonal gam-
mopalhy.^'1"1 '"'1, Many of ihese patients also have diabetic
retinopathy and this additional mechanism for the serous
delachmenl may be overlooked for diabetic vascular leak­
age. Other manifestations of hyperviscosity and second­
ary anemia in these patients include retinal hemorrhages,
microaneurysms, venous dilation and torluosilyr and
small-vessel occlusions (l-'igure 3 . 6 3 vieh0
3.b3 Sere us macula r delachm ent and Wald e nst rdm rs
macroglobulinemia^
Д-К: Thin diabetic male w ilh moderate nonpruliterafeve
diabetic retinopathy was noted to have bilaleraE m acular
delacbtnenls (A and Eli. An an^iu^ram showed micruaneu-
rv'ims btiL no reason for ihe subrelinal fluid, which could
be confirmed o r optical coherence lomojjjapby (F a rd Ch.
Olreervalicn was recommended, and a few months laler, the
m acular flujd had in с rented in bolb еувд (H anil I.. Further
i№ № ase in lhe MUiJatiwe delachmenl 6 months laLer I) and
PO prompted an evaluation lew dysproleinemias. He was
found Lo have WaldwnsLnom's feaci'OglcibunlFiernia anti Was
Klarledon сЬ е то ф е твр у and plasmapheresis.
К !i lu rb ra y 4зГ U r . КлИТ'п (.jr ih r x .J
Waldenstrom's macroglobulinemia is a В-cell lympho-
proliferalive disorder with lymphoplasmacytic infiltration
of (he bone т а now and lymphatic tissue, and secretion
of a monoclonal immunoglobulin protein IgM into the
serum. Clinical manifestations are second ary to infiltration
of the bone marrow and extra medullary sites and elevated
tgM levels. Pancytopenia, organomegaly, neuropathy, and
effects of hyperviscosity characterize the clinical picture.
Treatment strategies are complex and involve chemothera­
peutic drugs such as cyclophosphamide, riluximab, dexa-
melhasone, and eventually autologous stem cell transplant
and supportive therapy for anemia, and plasmapheresis
for hyperviscosity.
0

Л а к
m ш
 Multiple myeloma is a ti-cell malignancy wilh a mono­
clonal expansion of abnormal plasma cells in lhe bone
marrow lhal produce excess Immunoglobulin. Clinical
manifestations occur either second лry to the excess M pro­
tein, resulting in renal failure, systemic amyloidosis, or
recurrent bacterial infection due to decrease in polyclonal
immunoglobulins; or due Lo excess plasma cell prolif­
eration result ing in lytic bone lesions, osteoporosis, bone
fractures, anemia, and e*tra medullary plasmacytomas.
J teat ment includes hEgh-dose chemotherapy and stein cel!
transplantation, and supportive therapy for anemia, and
plasmapheresis for hyperviscosity.
POKMS is an acronym for a rare multisystem disorder
of plasma cell dyscrasia featuring polyneuropathy, organo­
megaly (spleen, liver, lymph node), endocrinopathy (adre­
nal, thyroid, pituilary, parathyroid, gonadal, pancreatic),
M protein and skin changes fhyperpEgmenlation, hyper­
trichosis, and hemangiomata}. Secondary sclerotic bone
lesions can occur. 3hey have anasarca and bilateral optic
disc edema and are known to have high systemic levels of
VliGH Bilateral retinal hemorrhages, serous retinal detach­
ment, cystoid macular edema, and optic disc edema are
ocular features.'""11)1,1~6bi Treatment by autologous periph­
eral blood stem cell transplantation reduces the VEGF
Eevel and the syslemic manifestations. ETerhaps, temporary
stabilization may be expected after systemic or intraocular
injection of aiitUVEGF antibodies^ 2
Courtesy of Dr. Ijeonard Joffe, Gass reviewed the pho­
tographs of another patient with mulliple myeloma and
З .Ы Uveal efi us ion syndrome.
A—F: DiEated conjunclival vessels I A!' and bullous relinal
delachmenl iri'i in it healthy 1.T-year-old girl w ho bad periph-
e.: гл I cilioc.boroid.il I delachmeipt Lind leopard-spol mollling
Dl Ihe pigmenl epithelium (CE. There w ere similar findings
in the opposite eye ID:. Visual acuity was counting fingers.
UIfrasOnOjjfipby sh ad ed diffuse Ihackenin^ of lh e posterior
choroid (arrows, Ь плг! ]■■.
G -L ; This 42-year-old Hispanic man experienced recur-
renl episodes o f sltcjlih delachmenl of lhe macula IG:-.
Anj^ic^Tams showed d ill use areas of hyperfluoreScence and
s o n » staining (arrow, Н]. He was incorrectly diagnosed as
having idlopathjfc central serous chcxionetirfppatfiy. lw o years
I,Меч note It'opiitd-spol changes th^it were evident angio-
graphically 11 and J>. There w ere m m cells in the vltrc'ous and
peripheral c:liochoroidal detacEimciilH. ^ix months later he
was legally blind hecause of bilateral bullous relinal and cil-
iocEwroidai detachment IK:-. Ten weeks after lamellar sclerec­
tomies and tt lefosLomies WilEiSut drainage (>f nubn.'Tinal I i'.iid
the detachments had PfcsoEved (L). TLLn yearn l.iLer Ihere bad
been no evidence of recurrence or" detachment.
lA-C bin<31frum G.i^a iinrE laltc™1* t frurn С i l l _3 ' 'l
diabetes mellitus who developed chronic serous detach-
menL of the retina in the macular region (E'igure 3.6]E-L).
Unlike the former case, angiography revealed evidence of
background diabetic retinopathy and intense staining of
the subretinal 11иid. Et was not possible to determine lhe
source of the tluorescein in the subretiniil fluid.
ID IO P A T H IC U V E A L E F F U S IO N
SYN D RO M E
Patients ttrllh LUEiS, most о flea heallhy middle-aged men
With norma I-size eyes, develop low; of vision in one or
both eyesr caused by serous detachment first of the cho­
roid and ciliary body and then of the retim [Figures
ЗЛ 4 '-:3 ^ ).й65"а7й i\itients may present either because of
Loss of their superior visual field secondary lo an inferior
retinal detachment or because of metamoiphopsia and a
positive scotoma secondary lo a serous detachment of the
macula. Dilation of the large conjunctival veiEis is often
present (E'igure 3.64A). lhe anterior segment otherwise is
usually free of inflammatory signs. Lhere may be blood
in Schlemm's canal, intraocular pressure is normal, '['here
are usually some cells in the vitreous. Initially the serous
retinal detachment may he confined to the macular area
and the choroidal and ciliary body detachment may be
overlooked unless ultrasonography is done (Figures 3.641-.
and И .3.651 and 3.66$ and Cj. Other palients present with
bullous detachment of the retina as well as serous eleva­
tion of the peripheral choroid and ciliary body [E'igures
3.64 В-L> and К, 3.63 and 3.66J. Typically there is marked
shifting of the subretinal fluid that is caused by its very
high protein content^ which is 2.5-3 Limes that in the
normal plasma.1'" :' '' Fluorescein angiography may show
some evidence of mild changes in the RPli early hut often
does not show a discrete leak beneath the serous detach­
ment of the retina. 'Ihe disease may affect initially only
one eye. Often a similar detachment occurs in the second
eye weeks, months, or years later. Lhese patients do not
respond to systemic corticosteroid treatment or anti metab­
olite therapy. Scleral buckling and drainage of subretinal
fluid often fail and may be complicated by hemorrhage.
Decompression of the vortex: veins in nanophthalmic eyes
3.65 Uveal eft usion syndrome.
A—F: This +5 hyperopic Ь Э -year-old тдк 1 w ilh hisLory of
Lfstuttalivtf aye-TetaLed macular degeneration in both eye:-,
treated previously w ith intravilreal bevacizumab, developed
pro^reii-si ve exudative rc.Ti Ич'ъI deMchmunl .-and lhe vinion
droppud Id hand molions Over 2 months. Peripheral tl>o-
roidal dL-4-achinents went? и*нп nil around in addiLion (Af C,
and D). Autoffuoresc-ence imaging shows mottled increased
rind decreased auloflirorea^fehce in the riLLat:hod ruling and
nt> fluorescence of lhe detached relink (9|l Following lbree
srdfertal w indow s the choroidal and retinal delachm enls
resolved w ilh increase in lhe Ityperaulofluonescenl speaks
It!'. TEiey w ere present anterior to the retinal pigment epithe­
lium as clumfis o1'yellow browrt piemenled malerial i h ■.
G - H : MjonLaye color and autofluoreHconce images shows a
nenttacEwd retina wilh yellow brown piemen! clumps :G and l-E).
has proved lo be successful.asLl-ft:il Patients often have a
prolonged course that is subject lo remissions and exacer­
bations. ihey eventually develop a leopard-spot pattern of
irregular clumping and thinning of the ЙРЕ that may be
most easily delected angiographically [E'igures 3.64И, C.
J E, I, and Jf 3.631. and 3.66ti, ]. and II]. The yellow-brown
pigment clumping is brilliantly aulofluorescentr suggest­
ing lhe material is likely lipofuscin and other lipoprotein
fluorophores [figures 3.65 and 3.66). Jhese are visible in
pretreated eyes and become more prominent, once surgi­
cal intervention has resulted in resolution of (he choroidal
and retinal detachments {bigures 3.63 and 3.66). In a few
patients flecks of yellow subretinal and outer retinal lipid
exudation may develop in lhe macular area. Severe chorio­
retinal degeneration and loss of visual field may develop
in some patients. Most of these patients are hyperopic and
if carefully reviewed will show gradual increase in their
hyperopia ovrer the preceding years.
Sftippnthic i-hr.].1LffuEioti S-mdrome I /
 Histo pathologically, the eyes show асаш ш Ш о п of
prole in-rich extracellular exudate within the choroid
and Clliity body; serous detachment of the choroid, cili­
ary body. Lmd relina; engorgement of the choroidal blood
vessels; O p lm al evidence of inflammation; Lmd expan­
sion of the subarachnoid space around the optic nerve
[E’igure 3.67A-CJ).’'I: '•* Abnormal accumulation of
glycoaminoj’lycans occurs belween lhe scleral fibers
I listochemically,- in one case- this accumulation consisted
primarily of proLeodermalan sulfite and small amounts
of proleochondroilin s u lfa te .S c le ra l cell tissue culture
has demonstrated intracellular glycogen-like deposits."'’1’"1
Abnormalities in scleral proteoglycans, increased sclera!
fibroneclin, and Lwi sting and fraying of scleral fibers have
heen described in nanophlhalmic sciera^3,ef!,i v ' '
The cause of iLJEib is unknown, it is probably caused
by a congenital abnormality ol" lhe scleral structure with
inlrascleral accumulation of abnormal amounts of extra­
cellular glycosamEnoglyeans over years. and hypoplasia of
the vortex veins.!'b,',H<,,'>'JU Forrester et al. have suggested
that IUFS may be a form of ocular mucopolysaccharido­
sis with a primary defect in proleodermalan synthesis
and/or degradation by scleral fibroblasts.11^ The obser­
vation of uveal effusion in a patient with Hunless syn­
drome and Maro Leaux-Li my syndrome [ME’S type VI) is
further evidence to suggest Ehal abnormalities in scleral
mucopolysaccharides may be important in the causation
of ciliochoroidal effusion in patients with IHEiS and nan-
ophlhalmos. '" Thickened sclera and vortex vein obslruc­
tion in nanophthalmic eves have been incriminated in the
pathogenesis of uveal e ffu s te ^ ^ 1-119^ 6
The following hypothesis has been suggested lo explain
the serous detachment of the uveal tract in idiopathic
uveal effusion: as aging changes take place in Lhe thick­
ened, abnormal sclera, particularly in the in ale patienl,
the eye loses its ability to cope with protein that normally
escapes in small quantities from the choroidal blood ves­
sels into lhe extracellular space.""' One of the primary
functions of (he lymphatic system is lo provide a means of
returning prole in in the extravascular compartment lo lhe
vascular system.''"' En Lhe eye lhe scleral emissary channels
probably function as lymphatic channels for extravascu-
Ear protein in Lhe choroid and ciliary body to escape into
the periocular tissue*96 Fncroachmenl on these channels
by aging changes in Lhe thick mucopolysaccharide-infil­
trated sclera, as well as a hypoplastic vortex vein system,
predisposes the eyes lo vortex vein obstruct ion and exces­
sive accumulation of extravascular prole in and waler in
the uveal tract [Figure 3.67153]. When the extravascular
protein concentration in the choroid and ciliary body
Uveal effusion syndrome; pathology and
treatment.
A and B: HistupathoEogic findings in a patient w ith (he uveal
effusion syndrome. Nole serous detachment ol" Lhe enjjor^ed
peripheral choroid (A), absence o f evidence flf inflam m a­
tion. FCjnuuH relinal detach menL, choroidal en^orgem ^#, and
dilated SLibarachnoid space (arrow, K:-.
C: l-tisLopatholof’ ii: findjn^s in another patient with uveal
effusion. 1here яг-е thickening of lhe sclera, Ihickeninjj o f lhe
choroid Eiy p e rio d s acid-^chiff-positive proteinaceous exu­
date Ia nows I, and lhe folding of the тгтет choroid and reLi-
naf piemen I epitEieJium beneath lhe protoinaceoub subretinal
exud-ale.
D; D ig r a m s of pa ill ways i.rirrKW^:- of Iransscleral movunnml
of extrratast ular protein Ktipplin^j. [. focal vascular leak ir>
an olherwise normal eye. 2, Aphakic eye w ilh Iransienl post-
operalive с iliac horoidaJ deLichm enl I hat may require several
days or Weeks for resolution. 3, Idiopalhrc uveal effusion
Hvndrome w ilh increased resistance lo protein oulfEow iind
uveal venous outflow caused by abnormal sclera.
E: Djijjfram o f suri’ ical technique for the InealmerU of <.hronic
uveal effusion. Note Lhe lam ellar bderedtnftiiies and scleras-
lomies 'arrows. done w iihoul drainage o f suEjretina! -luid ir>
each quadrant, avtaicfejrg Ihe meridian- of Ihe vortex veins.
lA .ir ir t b ( r u m V t 'r h t J i'll .h n r f W .i i l c " '' D .:n < f h fr u r n С а м . ' 1 ' ' i
approaches Lhal in Lhe vascular system, protein begins to
move across the RPE into the subrelinal space and bul­
lous retinal detachment develops. Jhe protein in the sub­
let inal fluid becomes superconcentrated lo levels 2-lVi
limes lhal in the vascular system, ihis is probably the
cause of: [ ]) the marked shifting of the subretinal fluid;
(2) the leopard-spot appearance ofthe R P l [3 ] the occa­
sional precipitation of yellow subretinal and infrared nal
lipoproteins; and [4] elevation of the pro Lein lewis of the
perEoptic cerebrospinal fluid lhal causes secondary expan­
sion of the perioptic subarachnoid space. Diffusion of lhe
protein from this area posteriorly probably explains why
lumbar puncture in ihese patients reveals elevation of the
cerebrospinal fluid protein levels in approximately 50%
of patients in the absence of pleocylosis. Dilation of the
episcleral veins and blood in Schlemm's canal are anlerior-
segment manifestations ofthe chronic vorlex vein obstruc­
tion that is usually present. The intraocular pressure in
most diseases causing ciliochoroidal edema or delachmenl
is lower than normal because of the lowered resistance
lo the Liveoscleral outflow of aqueous hum or. " ™
l'he typically normal intraocular pressure in patients with
idiopalh.ic uveal effusion is probably caused by the greater
than normal resistance to uveoscleral outflow.
 Ultti$Onograpby in [he early stages of the disease shows 3,h7 Idiopathic uveal effusion syndrome
evidence of thickening of the sclera, choroidr and caLiзг>г
A—L: This ЕО-уваг-old Caucasian w om an noted gradual
body thal may anted Lite any visible changes in the ocu­ dec Iir e in vision in holh eyes, left m ore IK m lhe rij^hl over
lar fundus. 3'his thickening is always present just prior lo J months. ih e W&a started on oral prednisone 60 mg for a
tmd after development of retinal detachment. JM■"':|- ihe diagnosis of c. h-i'jroiНлI del ach ment .n her left eye. Уhr? had a
demonstration of ultrasonographic evidence of increased hislory of hfeaiL (.'.inter lhat was treated w ilh a mastecJomy
thickening of lhe posterior choroid by extracellar fluid is 5 years previously Her visual acuity № 20/3(5 in the rijt.1iI
eye чЭлН 2 O '100 in lhe left Live. The rij^Hl eye had я le w yel­
essentia! before a diagnosis of uveal effusion can be made
low orange puncLile dots in lhe posterior pole And periph­
and scleral windows can be done. Ultrasonography may
eral cbofCiitfal effusions 'A . Ih e lefL eye had several amall
also demonstrate evidence of expansion of the oplic nerve punclate y d low d<jLh thfouLjhoui lhe fundus, JCj0° pefiplfeTHl
sheaths [positive 30е" test) (Figure 3.67R). Ihe uveal thick­ choroidal effusions and interior exudative relinal detachment
ening may also be delected in some cases by computed extending Lip lo Lhe inktfior arcade (8, C r and |j. Huorescein
tomography; and more recently by enhanced depth imag­ ®igi^ftram showed diffuse leopard-spot change in lhe left
ing of the choroid on Spectral is OCT."4'1 ey^ and hypofEuojescent lines fcarr^spondtag Lo choror-
dal folds at the equalor irom the choroidal detachments (D
Segmental- parti aI-thickness sclerectomies at or slightly
and t. arrows i Hie ye llo w dote were brilliam ly hvperaulo-
anterior lo Lhe equator, avoiding Lhe meridians of any
fluorescenl and Lhe choroidal and retinal del-achments were
existing vortex veins, followed by full-thickness sclerosto­ hypoautolltiorescent. Ал ultrasound confirmed the serous
mies without perforation of the underlying choroid Within choroidal :!Ci and r-minal detachmenti: (F). O ptical coherence
the sclereclomy sites, have been successful in the treatment tomography Ы the left m acula showed intta retinal and sub-
of IIJLS and nanophthalmos {figure 3.<5^Е) relinal fTuid in lhe m acula, and intraiolinal lluid in Ihe ri^hl
Use of episcleral instillation of corticosteroids in the macula, ih e underwent scleral w indow s in three quadrants
in the Ioil eyer the choroidalF resolved ovefniijhl, but the
area of the sclerectomies before closure of the conjunc-
serous retinal d-rilac hment r e s o le d over В weeks. The fun­
Liva probably reduces the chance of regrowth of tissue
dus of the left eye 3 months post scleral w indow s shows no
across the sclerectomies and recurrence of citiochoroidal subretinal fibrosis, increased visibility of the orange brown
detachment. pigment epithelial clumps IKJ, w hich are vividly hyperauto-
Decompression of the vortex veins and scleral resection fluorescertl ■L i.
halffc proved successful in the treatment of uveal effusion
in nanophlhalmic ihe author believes that
the scleral resection alone is responsible for the beneficial
effects of the operation, and lhat decompression of the with nanophthalmos and a tapetoretinal degeneration. J~D
vortex veins is unnecessary and adds to the morbidity of 'lhe author has seen two siblings with nanophthalmos.
Lhe procedure, ihis view is supported by the recent find­ retinitis pigmentosa, and bilaleraE uveal effusion, and
ings of Jin and Anderaaft. another patient with nanopbdialinos and retinitis pigmen­
Secondary causes for uveal effusion include ]ianoph- tosa who was referred for consideration of sclerectomies
thalmos/ldapBl^ jm3'M l dural arteriovenous fistu­ because of suspected chronic uveal e[fusion. The patient
las.*144"-1 scientist11 Harada's disease, benign reactive had no clinical or ultrasonic evidence of uveal effusion,
lyjnphoid hyperplasia of the uveal tractr luetic chorioreti­ lhe patient's eIeelrorelinogram was virtually extingLiished.
nitis. 41 carotid artery obstruction [Figure 6.13D-]), orbital i.ong-term follow-up of some patients after scleral win­
cellulitis, diffuse neoplasms of the uveal tract,,|J oxygen dows has revealed that some show evidence of progres­
inhalation therapy/'11 wound leaks following surgical or sive chorioretinal degenerative changes in the absence of
other traumatic wounds of the serous evidence of recurrence of u\real effusion. It is not known
choroidal delachment occurring during intraocular sur­ whether this may be caused by mild chronic recurrent
gery/40""1'' and after photbcoaEulalion.^* Angje closure efTu&ion or perhaps is caused by7 the same anomaly of
glaucoma may occur after ciliochoroidal detachment of mucopolysaccharide metabolism affecting the sclera in
any cause.'J ' LI veal effusion may occur in family members these patients.
;ё
 ТЬе diagnosis of 1UBS includes megmato-
genous retinal deLachment wfth aswdatpd cilioretina!
detachment, inflammatory pseudotumor of Lhe jtfveal tract,
diffuse amelanotic melanoma or metastalie carcinoma. bilat­
eral diffuse uveal melanocytic proliferation (set1 p. 1102),
Harada's disease (see pp. 948-1002), ICSC, particularly if
complicated by steroid therapy resulting in lai^e exudative
retinal delachmenl (see p. 78J/01, sympathetic uveitis {see p.
1004)., and posterior selerilis. [see p. 1016]. Ultrasonography
is particularly valuable in making lbe correct diagnosis.
Jhe leopard-spot pigmentation that frequently develops in
patients with uveal effusion syndrome is similar in appear­
ance to that occurring in some patients wilh systemic large
cell lymphoma (see p. 1160.. hig 1:!.34D-|), leukemia (see
p. 1244), or bilateral diffuse uveal melanocytic proliferation
(see pp. 1202-1204}. and in patients with organ transplant
chorioretinopathy [see p. 1 SB).
Primary Pulmonary Hypertension
Primary pulmonary hypertension is a rare fatal disorder of
idiopathic obi iteration of the pulmonary capillaries that
results in righl heart failure. Ocular findings are not very
common, hut when present manifest as dilated conjunc­
tival and episcleral vessels, exudative choroidal and retina!
detachment (Hgure 3.6S), or venous stasis retinopalhy
progressing to central relinal vein occlusion al times.'J''"
'J‘ ' One case of acute angle closure glaucoma has been
reported."'1' The resistance in lhe typically tow-resistance
pulmonary vascular bed increases, resulting in right heart
failure. Jhis in turn translates higher venous pressure lo
the head and neck veins, liver vasculature, and peripheral
veins. Stagnation of flaw in the retinal and choroidal veins
results in venous stasis retinopalhy and choroidal effu­
sions and prominent episcleral vessels.
Primary pulmonary hypertension is familial in 10%
(familial pulmonary arterial hypertension); the rest are
sporadic (idiopathic pulmonary arterial hypertension).
A female preponderance is known and the average age at
presentation is 36 years. Cermline bone morphogenetic
protein recepLor type II gene mutations has been found
3.68 P lim ary pu! monary hyper lensio n.
A—1: This 25-year-old white mate w ith end-stage primary
pijlmoiiary hypertension presented ] w eek before lung Inin*-
plant w ilh mild drstorlion in the left eye w hich was diaj=-
nosed .if- cenlral serous choriorelinopathy. Two weeks post
lung imnsplant, his vision decreased i.jflhef Lo 20/400. The
rif^t eye remained at 20/20. The lefE fundus showed serous
relinal delachmenl I A, ^ . А fluorescein лгк1 mdncyanine
green angiogram revealed mild w in d o w defect conespond-
Fny to lhe center oT the fovea (C, Df. O p lic a l coherence
tomography confirmed intraielLnat and subretinal fluid lEf. A
diagnosis of possible central serous churioretinopalhy versus
graft-versus-hos) disease was made. Steroids were decreased.
His tymptoms worsened Lo jjntfblve the riyhl eye Iо 20/60
and further decreased to 20/2(KJ in both eyes. The patient
developed a skin rash and looked very ill. AL Lhrs lime, his
oral steroid was increased. The vision improved lo 20/50
and 2 0 / 7 0 in 2 weeks, and further to 20/20 in bolh eyes in
aboul h weeks. The retinal and choroidal fluid resolved
A diagnosis of serous retinal and choroidal elfusion second­
ary Lo primary pulmonary hypertension was madeji since his
sympLoms began Ewfore '.he lung transplant and responded 1й
corLicostenoids.
[C6Uti«y (if Dr. Cmir .\U( .rn'i А1:1Д. Т!,тсш±н:: ■IjkVrL'iiLi'J., Hit l-teUr.il
A ll.* . S .iu iy trs 2 U I0 . p .fS b .l
in some of the familial and sporadic cases.9:7 l'he Lumen
of the precapi 11ary arterioles and smal! pulmonary arteries
is obliterated by cellular and myofibroblast proliferation
and in situ thrombosis, causing vascular remodeling that
raises the pulmonary arterial pressure'"" 'lhe secondary
causes of pulmonary hypertension are more com in on and
include connective tissue diseases such as scleroderma,
lupus, rheumatoid arthritis, mixed connective tissue dis­
eases, human immunodeficiency virus [H IV] infection,
cirrhosis, portal hypertension, and the use of appetite sup­
pressants.u:''' Since the condition is common in women, a
history of use of appeLile suppressants should be sought.
Death occurred within 2-3 years of diagnosis when
treated medically alone, previously. Newer medical and
support Lherapy has prolonged survival."""1'" Recenl suc­
cess of lung transplants has improved morbidity and life
Sftippntl.ic Llvi'iil Effusion SyndrnnfE 2D3
S U P R A C H O R O ID A L H E M O R R H A G E
ipotitaneous bleeding of a choroidal blood vessel may
produce a variety of clinical pictures. When it occurs dur­
ing the course of intraocular surgery, bleeding may be
massive and produce an etpulsLve hemorrhage. Risk fac­
tors for the development of spontaneous intraoperative
suprachoroid a[ hemorrhage are: history of glaucoma.,
increased intraocular pressure preopera lively, increased
axial length of the eye, oJder age. aphakia, posterior-cap­
sule rupture, generalized atherosclerosis* cardiovascular
disease, diabetes mellitus.. and elevaled intraoperative
pulse " " Clinical signs of suprachoroidal hemorrhage
Include pain, increased intraocular pressure, loss of red
reflex, progressive shallowing of Lhe anterior chamber and
smooth bullous, dark elevated mass(es) in the fundus. If
bleed ing occurs postoperativeEy, often during a period
of hypolony. the bleed ing may produce a ciliochoroidal
detachment of similar configuration Lo, but usually of
darker color than, that of uveal effusion (I'igure 3.69A-
C j .'35 Transiliumination clearly differentiates serous
from hemorrhagic detachment of the choroid and ciliary
body. In some cases, particularly following cataract extrac­
tion, the suprachoroidal hemorrhage may remain local­
ized and mimic a choroidal melanoma, a large choroidal
nevus, or a subretinal pigment epithelial hematoma.9
Huore&cein angiography shows no obstruction of back­
ground choroidal fluorescence over the center of (he
lesion, some relative non fluorescence around its border,
and usually some evidence of chorioretinal folds overlying
the suprachoroidal hematoma. Ultrasonography shows
acoustic hollowness of Lhe lesion without choroid aE exca­
vation (Hgure 3.69D, F-l L).
The etiology and pathogenesis of suprachoroidal hem­
orrhage appear Lo be dependent upon the change in intra­
ocular pressure. L'he primary event for initiation of (he
hemorrhage is thought to be hypotony resulting in effu­
sion of serous fluid into the suprachoroidal space, which
stretches and Lears Lhe long or short posterior ciliary
Suprachoroidal hemorrhage.
A -С: Tbis 7-1-year-old wom an bumped her «у е one day
aflcr th e undurwenL an intraoLular lens- exchange. W h ile
repositioning lhe displaced iiiLmocular lens .1 change in Lhe
red reflex was noted. She had developed an intraoperative
choroidal hfimewffla^e that was photographed [he nexl day
'Л'т-ч hi1: vision v.yi:- h.ind i: n-■:i :ni:- A f i Гho hemorrhage
resolvnd over lime with conservative managomenl and vi yitjn-
rrlurned I о 20/20 е^епШаИу.
D and E: A sem i I unar-sha ped brown reflex was noted w hile
this 79-year-old patienl was undergoing cataract surgery. His
posterior capsule bad ruptured during Lhe procedure and
anterior-chamber tens was placed and wound closed quickly.
W h en examined the nexl day he had в large U'mpornl Suprab
c: hTjn ji del I hemorrhage Lhal obscured his macula and coLild
be t от firmed on an ultrasound В scan IEJ>. Ten days later the
hemorrhage was drained, follow ing w hich fundus photo­
graphs could lie dune. Autofluonescence image shows alter­
nating cLirk and lighl linos- fqrrtEspo'H.d i пд I о lhe chcriorelinal
[bids at the posterior cd^e Erf lhe choroidal hemorrhage it ',
r and G : POslgJaucoma surgery suprachoroidal hemorrhage
iJ- in Ihis ЙО-year-old wom an 4 days apart showing reduc­
tion in s iie by almosL 5Cs-V-ih Cl .
H : Kjdensivt! choroidal hemorrhage in 1hiн 79-year-old male
who underwent ^ J/ltnettomy and scleral buckle placemen I
for a post Iraumatic calaracl remctval гс:ii:.■I delachmenl.
EHis sclera was very thin in I bo superior half and the buckle
sutures had to be placed carefully. The retina was flat al Ibe
end o f Lhe surgery and 2 0 % il-^ yas was placed. O n pos1-op
day 1, he coivplajned of no overnight pain: I fie gas had com ­
pletely disappeared and the globe was filled with choroidal
blood (H). The eye did poorly with development of a new
gianl retinal lear Hupoii<jf]y.
arteries, resulting in hemorrhage, iubsequenl stretching
of the ciliary nerves due to rapid accumulation of blood is
responsible for the patient's sensation of pain. It has been
postulated that necrosis secondary Lo associated systemic
vascular disease may result in weakening of the integrity
of blood vessel walls and contribute lo extravasation of
blood as well.:fJlv:u°-,,,|J
 ]' к
К ■g Ш ■
jT
_u_lViг.
V»^->
References 43. Ecace Rr KUjcik Jr JH FuTdus aul’^ujeS'STce ■ard'a senc-uE cxn jh ib c j I^
0|«^1оигаМ6Я12Л25-33.
1. to te '£ Г45С-.ЧКJsreuicfl з! te re in "ггг-а Cfhltdmoi Бос LK 1Йда471-ЗЭ. ^i. iw u n У Fi ih'fiia I. f.laRjais Fl s ! a. bihacec седо im aci^m al агегепя 1атвдга[1>/
2. Лгс1кг 36 Gainer "A. Eedmn тслкссрс issues cl едешпага! с1>хжй з ! ewrcti№!tral sei^L^oriaiedYipat^. нета МЙй'^69-73.
naMsaisreatHi. AmJ ^prttafma -56191 .433-57 15. Охе-£ A Mx S, el&. Th m iks cl ртсй/всеях ajfSE h fcfyxidal cnxorial
3. Arcrter j6 Gxinsr A MaiXacg c. й т ssceb a ^ x r^ rt. aid ig r иновирн; iea!j s -j hiaffiJxailrr xi: MtraJsaoEchoraiielsiflpa^.GraHifflflitlt Cli E>c OXiba^c
н к л т а н а ю ш ш neoesailamUm Жг J ^1№ пй 1Эе".:&12Э7-Э'' 20'0 2-3:1 C77-36.
4. MterM. MJbt Й; Flyar SJ.Tfe rcte cl rflraJ pigneni epitoeiurn i- Bie iio kitim suiani! Cafflfo-ti'ea,.CanrhaftT.ls:asVela Laig-tienmlbhNr-цзatcenfeaJserousretinofiachv
fam iiilratEn.Im ESt OXttans 4s >3 13eE.2r. '6^1-E2. h ISO^UKTli Djc iitilbsmai 195231J7S-66.
5. OKiUTB H.Ffjfjf.SJ.EKpeinenia idirelra п е а а д ц М г а н г т в в т и * ^ s n ie iiih 'a l 4:. Yan'r.zn LA. Sla^Jte' JS. haLlma-SFl ei i. j:a r щшкЛ cl i ftLse relhal ftj'ienl
п ^ ч е ^ ^ О р г а н Ь с М Я К Ш 11fl2-1il ealhelicfsty Slt J O^ntalral 1992:2:1 СЭ-14.
6. Fyan i,-. Ifa ■fe'eIcfmeit cl sr. e*pa n'cnia race- cl Ebbne! na пю ш ^аййоп n di-alam йЗ. toa: .CM. Litl t H. 31a!afii x\ cu: foa±Hf« retiiai -deiacfms ■
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120. B a ra toflHH f/a:lasiiK&.e:iil 0ш 1т18^^^1йпр%:1пеш )одв!кй ' 39 'Jelsan V ^ ii* R4 nVnLzii L. et al Мгерпйме Uealma t ci -dircfi с сапга жгсиь
anап Аю C^hlM-rd 1ВД1Т1П 223-33. ■diD'CfeliCfiTy. Reins 2'H37^7.1 '9-22.
12". '/,4itf ja U l;li}^ia l. Ai e^Lalicn x calcacb>d tieafln^it lor cenlu: sem i ' GO Eresde' Ш & esila S i ja ; ES. ^Ificsl cfiira^enslf3 cf CKfcical ге?лзси ar
cl>jDiElh^palfiv. Jpi J Gr Oputtilrfll 19^D:^:123-3. ntartrana.AfchO^sliri '987.105:3CS-13.
122, 7йи ;ja M. lilikwa £. Zem’a1ffiicus rtiomiftfiiBpaib omibicating iittetrt сспкнгс* '61 rerrLll F_ ts'ile iria jh fL ^ e 'a lc i Paiewof aiflH ^ w tfeam s.A ii J Endsfnd
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№13 a1age jh led Щ 19<"-72. M r g te fi D;. U.S. Gcntrriren: A il'nc Offices l £62.
v ial and -ealh Slaves. senes 1' na 229. »^£ paaica! cn x IFHS 83-1 t^S
Ш . tyran lG. Seri e там a1dsceneram ar ep cem с uq с cast лпса а с* nhes & Eabmae
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163. KaTHALetc. tfty .iirffti JF: й al. Ite F-radainnam Eire а д . Сийге art msja
i
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166. Кат HA Le Ew и. HU, GaM?y _P er al. Tie Framrgin;- Ffe 31jc^-. I.AssaclalMi cl
acfuhDimic piirc fiif nfh anq e Handles preraify nesuec n fa Ftaiinrtani -ealSlit?/.
Am-ifcidembl 19?7:1ЙБЕЗЙ1.
16?. Kav №, Moa'enead НЬ. Elal^a or tlndness n lhe model -ewnny aea. 1Э39-'' 070.
№sh inlcn DC №t onsl hsHutes cf Hath 19/3. CtfШ pitfeaifen № 73-^27
163. Kh M\1 Ldbowitz tfr Cutai!. el bl Ptm lenraor see: с сайга* Gallic reli cpitv.
senle macular ^делавЫп, and орел-вп^Е ^ELD«?)a h Ihe Вшп^илЕуеЕйму Am J
0]f4ham 97835:23-34
169. ten BE ton fl. fttaactaandimoilsr зедэгешвп л йегАпншге toh Ctirthdmd
ш Т З и т ьа [Ела1 лпг ia a
l ,'0. Leix- ..!.■:-M. duster DE. f.'jinoe' 1Д er aJ Jx F'am cgnair Ere Stjty rvufiograpli: an
SF^lhamao-^siJ ^nd aptdeirc+iqica ejck of cala'iait ааяапи. daaefc.reuncfa:™ ma^a1
dece1'кгол-ш. -and лиг! acu tw:n г детски эд j al on cf 3631 s ite , 19:3- -975. ar*
ЬЗРйалч).'-90O^:3aE-G1u.
171. MacDondd Д£ С а ж cl nnflrea In Canada, an a;ayss cf £4 '303 -ж к reg анес re
Сапайгт Naknal in iln s lar DieBind tin Medteat. ' 96332:2ё4-79. '
172. Mai пк -oS. CsirpKi Al. RrnKen J. el a Prevalence f cc Jar dtease n a x$i aicn ducty or
slU в^з 35 hKrs dd art a*te Am. Qpntiahid 1Э92;£4.' &1-Э.
173. Ml£j nnasj P. iraiinctiani ^e auev ^ir J Cchlldnd l &7&ЁЙ 332-3.
174. й. I'-i nada"K and causes of tindness пE ila d and Ш и l &4&-1ЭЕ2. jcftdor:
Her Wa est; e StalHisrv Ohfs; 19ЁЕ. Чежгз n puit Iran- and ;■tedcad ай e^ , гл.Ш
173. \\ttnx ^ РП-]осса>риюап >nt n e i p i nl пйсЛ' laaana. Csrf i lit OdHM rrtiw iл
М Ц Щ Mi.': и. km 197' 1:507-12
176. Lcndff; K. Betrdmzu slhaajicnen^n^cmie des^joes. A t r e Jlo &jelK ^
Ojrthahto I8h5;l:10&-13
177. DciHE W Ren a1oa d&ji cl с спа ctcumn^ in cl die w x lamfn
Tra'n; Oanti rrcl See UK 1Й9& 19 71
ITS. Fimi S, e^ tl J. Eitie clrnoiS cl ncHajq je ce la niili^a iHErtLnese; atlslcr m als'anl
3Ly«ipe № i deanerescerjoes f/ilrei du ой!е pasler ieuF. Qpnral^cttjia 1^32;l
179. HalfjGUie LH. fe^en FD. A case cl sitsrticcl ft jador^n bs al xaJiar tomar>daouaiJ
auia! cn. Trars OpKtal-cl Soc 1й7.17й2-л
150. HiKTjnsa ■J. &f1TdiKlnsil cetera t o гок- 'кпа dазам tramiM n senle ш и R Land
OJJnamc Hcif'Flcp 1BJEft23l44.
161. Jc n ii P Kiihii r:. 5s acte tfiific™ ? Errtatrq da UettiaJirine ресепшн n a a is
meaediSLitaKi^Eelii:^ger i923.
182. 03 er JM 1" Eflrgnia n J edtp ЛЙз seJlEner c^M'fil'nciiop'iscl jer fettnje ^ua ech
EjgaraurastafelnaidHnfelE d? ^*ilhiJn>:c-.ca r. 3ecl:(n ;■. :at XI.JBesbacfea 1900-^924.
183. O'mavl m. fo r cases or t o lte й&зеггпп tn cf (he macJa lulec. ^\a -щ Ив
l £27:77.16-21.
13^. £eddcn JM. £har: The ecoera ctot al асе-гйэй: macular osnccs'al m If CchltdiMi
Oil 2CW-^:17-39
1Э6. (tear i, .ifle L Se^fe mEiifcr ensrjas n me ЙаиЛ1гш. 3f J [ptilltfma 1978 62:
H^-50.
1Э6. Eta el M. telrag и Ш k der Maoiadiaai. J.r:i Чспаил ^gafis I^jg i £73.' >32
32Ё-31.
187. Deulmii' tf. fiJifis AM. ^el cuaf d^lnmhv or f t ral i^i ptaranl egilneluai: 'i^lrcpia
rociL.1a t tmr-ae п т в Л Ё а rsnDe al -. nc^ren. ^cn flir^n a ' £(9 32:5-9.
183. FutoJ "G. Dn.Kf! aftne relinal pgnenl sfilld urr. i n ' CpnTamcl 1ЭП :l E.TIHF.
189. RuKjs G. Cil I t ^f>s!3 'iTfI en rJ. Fam I a. and SEoatoy <тлаг-: -tsla oje ard Is /Лcnil
япЕйатг. Тгепь ^ir йгас 03fJtf!ama: Ola a^rjga ' 9? 17533H3
190. R]ikiE "G. Sftte&t'.'. Artier C. ~f-i ulraan.clj e cl crusen. Дп J Ijpfltamj. 1&7l;7'
1Ш6-ЯВ.
191. Fi eilma! E. Smlh "Tl Senls claiqs v te tonrapitera cf me patena Kfe Tuns Amfcad
ODfiraTTB' O ia a ^ a l * 3 69Й2-6"
192. GaH.DM.CncfciilnKri^scijlar- ^mbiines-lnes hBJ^:alictia^lr&aln>erl. "гэга An Acad
Oji-JCan'sOlslayigai 1973 77:2P3lD-CF220.
193. Gcfj G. :r edr'iin A, 'M s Gff. ^lacncfln aanle matJa dacenerabDr. Am. Opnrolr^I
l£yS76 ?0H .
№ . Klen fi. Пел EEK. jniai HF. PiedErci cl age-nelal&d inaaJafanf. Ц-t BeaNer Gam
Study. Ottnair-a^ 19S2:99 933-^3.
193. Fajatt cn D £trc-n;l?a Щ Wnasiiir D. el i. Ii jsa -as nil; lacljs in aqe-relast mxu ar
dsetEE.iijr J Cphtfrimd Ш . 1>M:3H3.
196. FeaoeШ. !>йгй^hmeyccRibretinaldegeneration;dпьа a>dce^tn feanir-s.& J
i № r a I0 fe5 2 :?a4
19?. Еа1йЗ-. Druia afrd: e: realtrsrt'tc: senleгйш1зг Зеасчеolnfl.Дивгj ODftfianc
1SS&& 117-ас
198. ТапЕгшит rt_ Esnaqar M Serie fcflr Cfrjenefs^Dn d Ihe m ails fa aTer е?ч-а
llmreaHin ала cgmjria aljty. Can J 0jffl;а та 1Э72;75й(Й
19a. Eanmdes 4 Pbl ГайиН D Ciitia rr It, er al Gsie a al -l-fier u. j 0]Г1Га M
шчпэо-г.
i'UCi. Gik M . PGllixena s cf с& з& т detacfimert cl Ite re j aeprt eium. 11. Senie iMfcm-
тэп ^ йвд пнзйт Am JOpfTtnahBi 1937:£S6' M fl.
20l. ^ n d e r tff. Пасиге Mj. jerian Tfl e al teesima t cl iisuii lunclcn t p a l™
ace-iealffiiraailJdegei'fl'alcfl^rt fcwrcusi a:ur,-. A'cf Cfhhalmcl 13fifl:1 ffi.l5i3-7.
232. Е^тег A GttJites '.0 Klesn '-.1_ e: al. fi3tna"3 aelweer tondia д а а 1агх and functen e5es
rtliase ielm ha; e*jcalr>e age-reliied m aJa1Песйпег^а- Г'/ей Cpmnalncl 'in £c '
lanaza-aa
Ж KleinEf ЧС. EirerC,Ale:^dft M: й ^ .сап ш зе щ й ^ т^ ^ й и й р п ап й г
decen? ilixJjicn CfMniimoi l £66: ;ffij3b-7.
304. Lenna strend a Aft si ап CO. Согаз: Krailf; ty in ^tsc-jca JeceneraODr and the ie alien a
iitien rt .sjol (TFar^nlAlaCfhitiH'DilBa&ti 225-32.
235. Ha'^tirFl'clacKifluialjcfl Sbjctj ^otp. Laser рг>:(ила^1г1а 1ol atU/aal r£j/sa:uar
kaans n ape-rebtfrdrcaLlaf'tgeneralicf: reafs !ra rand'apizec diacalfal ^rch
Ш а Ы Щ ;1И к1220-31.
Ж. maitirR'GlacQaqiialH! Stuc^flaip. S± fd ^ И л а й teMisin iqe rslaai rraoitr
deoens^ja': cnMlieaicf e^Ltilicfliffl healmecl г the M iJa 1FhaEoaaqJattnSljft'.
Aril Omtiainoi 1991:105:1242-57.
237. Eunneas.S Jcfn ian ^ Waisci FW.eta-. Fjelralseralr.'ti't^'dnisenirdnaidmsen^eae
a ilLtfy js га lunds penmehy ^Jtn Cfhlldmol l £E8: .06.1031 -4.
Ж Eiin^as ■£'.r.lasMl m, jamstr- № . eta. Dnriaiec ro^eii ieninhir, miy prDdci lhe
dsf/efapneTcf a'J^ffic a^-rel^lifrj;^laJir■jcga■Jerallc^:.C1:hlhгlm]iзc^, l9SJ:£t:375-5l.
Ж Ftfrran £A Сагазя C.F Jiran II lhe eiectro-oculograni г d(frBS[Jarnl^ drusen. Adi
OpTta:^l 197^^4:23-3.
2i J. tiai. JGM. Cn.aer a x tflscitei n -'jejia- dena^a eT and t g i eralcr. ъ J 0ртга1"й1
197330306-17.
211. Ma'tLi H Meti £ Vrfl M. et a; E earopfjgtf >5; sra n ааей'чем оt sen e macjar
dBgenaaknAnnOptTtHinKi 1963-:i&i35-B.
212. Jlaii'pa LM liesch.. Face, ra id j ^зедепеглсл. a;d Ihe rraciilar ffittocaogu alcn :tLJf
tatiOitttarrG '9d2:11D:l£99-7'iO.
213. Еа^ек Jv. 3 egel E5. il'asLint Eft. el a. №o ::-reUBl Lr>^jure: i gma ^r; oaltems cl he
pa ftissl luni.^. ОрПГаГкИсди' 1S62 89:115Б-63 '
214. [Kj^r E L гкге Ceienetiia en den certaheo -e! па en P gmerteu iheS: Erne nainct-gfiai-
andtemKhe Si-ak. Лtied-: 'лп &aelei .ton <in bp CpThal'tl l973;l fib' -l t.
215. DalrranAF.-anser Lf.iAA.Darinanl^inherte'da j b . ci Eatlsrrem jafl. 3r J Spfllhamoi
1970 ji:373-S2
21^. GaiXH.Cn.iena'JGa&afam MJJardeathnieaWdegmHatli^THBAraCfhtnaliid
Ее ,972:70:4C£-36.
217. HLn ph^p '/ll Ca 1зос R£. ftlaie Jr J№. is i e reltuir fcjth mcrf deqeTeralc-r. Am J
Opnfai'nl l984^E:7l7-22.
213. Levis H. Syaiiavd ER Rr: el si. fte д й ■deaereralicn -уТй a cmat ea the 1jh
0pm^:-clcgH£^92.l4aE-a
219. fresiler Ш. Breida £E, £&im .M. tr. al D'csn dmctEreics i и ! епк Ji:n enid^ue
-tr3Liijcne.tcal« ai-reBDednaai-: JecsTcrjlEr. ^кпа 1Щ 11Ю -14
22^3. Ere^ler SB. ^ g Jie MG breslar Ш. er al RelJUx-stip of си-sen a^d aa cwa Hies cf
Ihe i йгй pcmerl ep thejjn oc-Ihe crocrra a cf пелтая:Ja r mam ar г»зепайрп ton
Oprta nal 199П И :1 442-7. '
221. Eiic “JC Efjch's nemtrane tonpe Ш 1a^e. BpJ Cfhinal vd l SS2.76:166-2.
222. FaJe Hicff D. Chen JC. Ehendm IH el d. 2-haads perijs cn ifla-mally a ir aje-mlale-j
E1jch'a iiernh'^ne cneoje. Amj CpThaf t i 1990:1C 9 2 1-7.
223. Fi^el &. FaIpaic It. [hchHr, H. sl j . :>]iu!nr 3 ape-reiiied na;Ja1d:ti Шип v.ii'.
tinniifcI re fis n Й¥Ш'[] Itt .^Л! JCphlhilmi 1£&2' 13j657-61
22J. ЁспейгA teLhaiaer L Ъхеасепсе chasder sl t; a' drjsa' Cu'i x indK?^ire-preen
а тс+ н ^ a^] me r pcsab s acnelaian VAlh cfi&'a ca p-erliiiw. Ger J ^ Ittem }
225. Eheriit , G. SlenmEtz R MagiiiE.. er al. Core alcn stweer; if+ds saaded mai Brir^'s
memtfaieaid ace. Cctilh^n>:<Ky ШЗ:1С0.4г-51.
223. FaJe fcncfl D. Ha per -A M ashsller al ^jrc tortss m Eract: e nema^e; j htsladisnal
and rrtTf>](adc s Д 1.Cfhlhsimdocv 1^3.37:17" -8.
227. Elits fi1. fees^H-Eu'ns L. ClntfHrmrptatajc и 'e al cni al 'luia'. of Erjch's nembraift
Trans.An' CpTTalrol See ТЗЙС^аЗС'^-гЕ.
22S. Odfei'AJH. Bwnilesn £. The crwalepx cl mstJar d i® i n Mslmcmr efs. An J
Oam:a:"tl I933:ll]-2::I>7T
229. Fepn?y B jn : L. Bins 4F. йаа ^...Лде гйа1ей ггЭ'^ег cnaiga г |!.:1иле mr £С ^чоге се.
Am Jftfrthdmd 1S9Q 109:2йЕ-73
230. F'aik FTl. Green №. PcEa^. R Зет. e macu ar ceqenei nan cln cocalnctiqn- н л йа! cn: у a
ease i 1Та рчейк^иг ECige.^ur J СрЫпа1п>а 1?73'75 3S7-£4.
231. Gieer '^R. K?j i Sli. 3en t тзеп ar aecenersnx; hзйсalnc+Dgc sfli-d-. TrinsAm 0jnTfl me
Sdc -.977:75:1££-23^.
232. Hoqar MJ. Bri>?h's ms tiane and ia a H d Ihe naajs rde d eastt teaie srd acf t'jen.
Trati Gpntnalnd Зое 'Ж ' 967 87:113-61
233. Ealii EH .^jann and -dccenerallcfl r the песJa- гея cn: a ar-tcc-namiiiaaiial slu-dy. Er J
OanTa:"fil Ш Й Й З Й Ь И ;
234. F-ernEry-BjniL.GaC'C-Tn1^ №1укшпа enr^mac/lachesiiil^orhiima'FPi.Br.ch^
тетегглез'а dmsen I'wesCchlhilma'ifeSci 19S7:2&:1 '3£H7.
235. lih ta;h: Т. РгГегмг P. Oa jshi V. et al Fa milH' cl dmsn mlie huma: ене Am J Cchlldm])
1986101:342-33.
233. khtash ISorgenteN, ^orsoriR d ъ. ^itcgeneieTuiKr in fa a i iale.ln^l
CfinfalTilVfaSd Ш 27:1М -!!а
237. Машгк OA, HewttAl HifiWt etal. B^tetiHi cfspecfitertiaBdLbrmahiJtmdeaifesbi
ilmsen. B'udi's ma'trane and с I ary асф Am J C^hlnalma 15f! •.' 04 373-2'
239. Heqa-^ GS.LulnerPJ.yanrCncfp Ul.ffiai Ал П&з i:ed h^adheiis inairasdefi rimsen
as hnmaheis d imnuie-ned aled prcteases j: fa FPE-B'it±'s memtrane :mertse in idno
ancage-re^fld iftscJa- detfl>aai>a- Fmq t o EfeRes 23tl;2&i'£-32.
2^3. FlesHI SR. Mdins 4F, SchneHr B_ el a. Ltalicfl. зЛеЕисйлв, stjC etmpoe l>:r d aasal
!ainnardL«(i aarpaetj wlnd.aa' a;sc*alee v,Tlnaqrfl andagerdaed majJa1
dBgenetslm Am. Ортпатс! Ж С:129t£t6-14.
2-40 Gural l : и MGtf; Cdlua menaiem: 'eso^licn v a jsar atier aseгwag Jai <n: я
ецийтепй t o >uih Gptithdmd 19в5с10ЭЯ№-71&.
24'. B'euer № l !!iMa JC. B'essla £6. e al. Cin Dopaflologic mrelal on of arisen xc relral
ngmart sf-lhel al atiHrmcl lies n a;je-retilKl ra o ia Jegereralicf. Reona 199*1 4.13CH2.
242 Cneei 'AR. Engef О. Age-reltoJ i 'flalii deqeTeralic^ hsifalictajic stLCKE Oanta irclc^
1993:1 Cl'519-3E.
241 vifldEf Srhhl.U w /tW .deBunW C .eia hmiHhandrarkal iXLanJetalai
imrescqpy °f baja- la iiiir ftpos L Gaeles t o Cin -jo Cfhlldmol 1SS4:232 ‘ H .
244. Lo r ;■ KJU Lee VW. a aassl laTinij -jemir LflicpLe la аае-те aled п’эаЬг eeaercai cn?
/WiC№Jaiuill992^(M5-1C.
241 'ла1def Stfah~L.de Ef.rji'.WJ MooryCM.el a й ba^il amnaF iritpje \y аце-геЫе:!
i'da.l^'je^Te[alicfl?Afdi Opitalrfll 1991;1Сё :42£|-5.
241 Hscan Шгййгап [Щгвоат c: 3p.ci siren ixfl.TraraArAcac Cpirl'fllrcl Сйзиг/тос
19о5;ЁЕ:ЕйЗ-М.
241. Hash na У Wane *, ИШ ^а -. Ajnq зйязйкв of reiiia and chaori d Ja^neae: jgir
rsEro e^islJiycf maciilar recta', cl 1?Ё e^es.JpiJ Odd'a-fro l9t4.2fl:6S-l02.
£41 KoirF.veic AL. Chxcsi i' me ctoraapibris assccarteo -..lih ierile тки ar снегя ю л ton
С(М е Ы 1&7Ш53-64.
241 Penis a F. KJfogMcrti M. bart:: 1 An Lfl'asln.ciJsJ t o f э1 Lie ret с! Ie o g te and
; trcb asia in lie tre s to r el Eft о в =■*maxe. Ajg! Cairalricl 193^.1 . 207 &eenW3.Chi»pattiotogicS^ffitf M ^rtHodalrieoEsculajiTienfc!^ a ^viewand
2БС1. Sate SH. Seri e сПэ^сз! ec erasti. 3r J ЙрМи1тЫ1£7157 93-1 fir.
26'. SakE SH. №■ 'iiit l fcfTTfltHi berear ms 'el ni реггет etire :umin seile eres. 3f J
0pliltt*nd 1973i&7351-6&
262. Sabs Sh . Cri-aer piTsira (jeciipx ng а сяспцт a afroptry al lie rebial igmenl camelin'.
^ и с^ ы тслэеги & и . ' '
251 Smai f.'L.Greaslffi ^Ie t j J Bi^.5m fcrnacd#deffiiHatior:ai^iHBaMoMarElfiffl
cr №d cases wh TefftiflftfcRia! on ftnealh Ihe retitii agnail еа11йи(г. t o CFtinalmcJ
197Й:Ё4:№;-7.
2У. k Iirawofli fhC, Saite J 3. SaikE EH. Махзрс&эв г?1ш! la Gutfii msntfsne n KfriflalK
naalif jegeieiElicfl. ?f=’ 990 itfl 3-21
2E1 Fne-i'ian:. Sjrih W. Ки^аига 7 Sen le chof'Sbl ^эзеш рйМш and arisen, ftdi
0ptrtftikiKii96ae9Bffl-3a
251 ln>D^enw ^E&jen; l llH ^ c a с я т к w р А гЁ \i IT [>Kt?f cr sitrelral
гаjjfflciilaniKa'i and sicalme aje-re al^j n a ilif 'tga eralicfl. ^raete] t o С n Бр
Cfhll^n]! 1ЭЙй2К 313-20.
25r. Lff.'iis -. ^Наитз B^. rcas ^V.Ch-Df^iflna li'c u e m JM e e^lramacuii' arisen.
CfhlldTBtacv 1953:33:1 Cft-112.
251 Fexjen L.LiiJuidn а с тгаш rhima'.rej'njJ agina i ealti^ij i (Ilhscstcs eiL^me
fttudieniia, and p.llra:lncljsI Etuaies. Г к е ^hinlKri V:S S c ' 97:3:1
251 Fh&Jnan: mai Biskra EM. Fneta g£. e! 3^r*^nssis d sens liscncr'i с&цепяэтап й
Те тки а. Сатскгг ОркТдi wtgicum И . к,1е>н, 197k Acla 19'l :l .4У-3."
261 Сгадкса; E5. ;h.dcrG !!F: F^crnr £. ercl Dsciitnn eegereal an of (he ш ia. ll
Pilb jeflas.taJi OXffian-s-. 1£719i .755-7.
26'. Pod£ tIA trfK^esis w n^ilar dseaje. T'at: Дш Acad Ссштито^ Л:15гггюи
19ав:УС:С6б-32.
2Й. ip^Sd^l^M M iirC M .-deBiufiW C .M rtElfllc^iclEaliureEclltBea^ibpesclape-
гйа1я maoihf dsgeM Sir 0ртТо1"с1с^- '95299:276-66
261 iiertiKf FH G'Kstra l -F. ^ е з е г к е я (iiQlomi dae Ш ух cl lie п а^И t o
flgiTpntJ 1flB7;1ftSei-fl&
2Ы. Zsdis le FR Jiitilam le-^a-cl Ihs raaila arru^iirg а теид та t o СДОИпй
1^:Л:5С^7.
261 isi iDdsM'<'/fttanite fl, -amiKra S e! si. b cxerna r ^ 'a c asls'aaa a catlfairha m
a palerwth ^fericl^iisei'pm ato.a.B- ]l(^П ПзЫ 19SC:r4 ^33-t.
261 Hd: F l ShsfaiJiT: G. fcilei Jidt С. e а1.Лла jbс cf I pio asxals еИгктес ircni xran
г (ЗЭ-lif if с per plfifiJ Eji.ci s nenfcfine. n j Cpid'ihcJ 1394:112402-6.
267. At®naon ['-. "oka ^1 Fi^esl M e! il. Chiralff zalcn у tflla orr^d aestnUes ii
ctjkt. ilieceKiilsaiKflafej win sere aTdaae-relaed m ^Ja1detensia , Ew9/e Ffci
2009;УВ:24Щ
261 Гл.I its Ff. fijsse I 3Fl ATderaai D-. e: al Впмп ж к н м w'ti ajn] ard a e - t aled
rsja-la--iege icraJc-p Kflljn j^eiTa'ammx lae}Jii££jlLl3f depaLrsiKaailiea'.-nir
attieTEdffHi. ebstca;. i'lfyla^EE. a^d dense Jep*].: osease. FAiEB J 200C':li:B35-№
265'. Ha insc № . y.'eiiEf J Girsa к eL ai O sEtltaai d reli al ppnenl spnsj al tielKhmsrlE
asjKflled'.'.ilh d-usei С'эиеЛлсП 1\г,Ъ ц ^fltiam j '952233:11-'9
27C1. Chjing 3_ 3rdA l 1ч aiffixerHS cf le^: si 1те reti'cl ftgmenl eallteinn'. AmJ
Gphlldmd Ш 1 0 6 2 Й Ш
27'. 6 rd AC. t o u l J Ffehijl agmail eallteid oela^mei tE m lie elffl^ Tmii OJltia п'з. Sce
U < lS£ fc'K i:4 -£
272. Hftera SW Ixbx-; AA № № p r.( пе Hth aa- 'slatad n 'o b r dsgaiHaliii. ^nch
СрПШ^та lE fll'ffi 651-1 '
2гл iaiilM t И . С'^ггы I-J. Hainen L^. el a. Er per neinal i jser. fcnroucfl nda^d
inlm^iTKJariKgkEide rjectmn.AreJi ODilhatre; '937:1-3&:226-13.
2i 4. El Зам F. Спеет Wfi. Fleis^ira r J. el а- ОпсмаЛЬдц а сате1и>>! с! laduilcii ate
oelKhmenL cl lie retnd agmenl еа11йил\ Am J CpTTalvfil 1953:101:676-33.
271 Fei ft-Euni L, vm rft, <eir h'L.el a MKuMaJthhctfsncfcuaricn^ft. а Е«те(эвео
; иае:ег anjajifflic aid uhraliaral slid;. A'ciC'phltifmcJ 190l:996l>i172.
271 FiTe 6S Lpe aa decensf^xi al Ihe rejnN э cma l ep maij i .^ja J Gph!Taivd
1931:51.4651-73. '
2 гг. o i'j.ij п 1 3Р|'тгл I й. rrecjReiicrcte{li Q. et a^ hiLntfiilc eg (d EHidf я1GJDrsinil
I'lemb'aies mas- 'йа!я? л:ки1ог йкпе'з! <л. J x J Scdtnima ' 562 3S:^3-5l
271 B-essls №T F-asl W. BiesUff 5E. ecal. fhSljra Edi'se al к*'[у -defiiec ^сгска
гe^ a;tin :[n ai зазос al&d w ih macJa 1decer^a'. Агст Cchl'dmDi 1ЙЁЁ.' 06.
1537^'
279 Eresde' 5) wlJC, ЗгеЕЛе1hW e!il. ttncofdlhoiMEOGrealicfl JcccaTcKfcrd^
lecoasailaiialcn n &pe-retUfrdгй ?.15г -degts eralicn"Afai Gpntafcul l992:llC:S27-32.
£i?j ':xis К Futln JE. F aik FtJ. el a. H:-j;ln.;?.i rJ ^ iK r t f if e n a y ■
т alfediai тес^кгий
mai:drana п ке-'е aled ."dELla degei'eralicn. Сриш т^ку 19Эг2:Э&136&-73.
231 rreae:icK Jr tivty MG. Tcpa ngTfl. ^ al Pk a a ffljtk cl sipaed геппа э grna i
galiela cetcnenlE: a^g' al кэЛ Tea^aaailinziiljcn n aje-iehl^drcEilif dega eralM.
нйпа 1993:12:1-7.
232 Sasa JDM. Ектнлнсерс i sncfiaT-clcgic Kflsceialws rega'd ng Lie feasti'i: or sjgtal
etctn'DrsJlChtiJ riec^Ei1a meirbraiea.^ir JCfhlldmoi 1ss“ .' 13255-51
233 oas JD\1 FialhKeiebs cl a a:rari c'elKhmerl ci iie ееj'Kp (be,j i W.Fk cdesc^n
irgc^iaaa; sue; cf aenle a:c fc'n1тки ar aegeneraiai № JOphtfllind 1St7:G3.
S4E-59
23^ oasa JDM FTeaenl hdicsrt ens ax fela-r а т я у te hrxprDT-1ш . r. March W. &dilx
[jptilhamictiMrii^jremJricilaiei.'niaTfaie.^.^areEB Slick |ШБ4. p. .133.
£ S SasE JDk1 SlfliBM^p с з !к -уnaaJa Je е к к : daa'csi; aid (r-almat 3nc &d. S: L ie ;
W i i i l t t p. 19-217ВЭ.
2 ® jeh1; m Henal ',VJ. Je Jian j E iiaTmiiiiicn ^&^n:n mcaiEcpic ilurff i a aitrEli al
■diaTiiJsl nec^icda mfrtreneae ^agerelaed ma:Ja' аедашЬоп AniiOptmahilBt
19Ё2:''0833-7.
TtKtt ts'.4'амЕ. Fb I ra 1931:1' ,323-E£.
233 5fe«n 'n\ McDcrnell PJ. teo JH. Paltiatac sealu'K г sffi e тк и ar смепаг^эт
;^ihamaa?M^E:K:6'0-27.
239 ofosinbjG !f. \iainez Ж BtoH iW ,et| I'inLfiaa'icd'emtaJa'ii hateienKa.
j^ d iH 'D f sjjalveicaed Eiifelra newasciai mmbants h age-retled macJjf
Jega'eralcfl.Ai" J 0]CltiairS''5e2.11il:4£4-72.
29j im Ff. of'Bin4iiau; №. Lurhevl -M. e: al. PslhdajE ^ealj s у sjg ca?v енейеа
susTflca nec^ascJa meiitrans n age-nslaiied maoiar degeneration.Am JttoWiamof
19“ l: "26i7-E6
291 'tlim a ee fL 5emjs an her tniigic dGcricm oelKhmenl al 1те тки а. Тгаз Picf Csl
3tt-0]hha(rc Sccl959:4t:l39-S0.
£92 Sitm ne C. 5^taa G, ^ al. Osut attrelral гел-^es^U г ade rebleJ macdsr degeieraba:.
'ialum'HsT^a'c ea^'laa LwenLCfhlTalmclogy 4»j.^7|5i*4£-5r
293 Teete'aVW, Eird WC ^ claaal ilad; tf ^e vas^lanh cTseih? cealDrm macjar dece laatta'-.
Щ^ОрМнЫ
£9^ TeeteSyW, EMAC Tie с?^эргетс^ r&iMscJairjba' nl sails rfedkmn macJa1
■Jega-eralc-n. ft"i J 0xmaira; ’ 973:73:1 -rl
293 5аи JDM Serous rslral [>: ■ ■
isn! epiiel a ceiachmerl rtit. a nxch: a sjgn -i cecu Lcxrcifial
Teovaaailinialan.Reln;' ж:4:ЙЕ-2А.
293 J' 3£\ Ж Etrcfldea M Haniloi №fl feite lear cr ms ranal pgmer: ep me\лл It.
5^lhima 15® 16:7-1 a
297 < eE JC, b'd A l JaHapiLi lar.- ^tyaJa n&a.nscj атайог n elder :-alienls. Am. Op'Jal'ial
19fl0;K&11-19.
293 Ifls^heb <.Green 'Afl. Cranjsmilcus пекись la Bn^ :: m a'tfa’e n ape-'e alsJ r aEila
■Jega-eralc-fi. t o Opntaivfll 199^:115:ег.З-Э.
299 ййЕа JDM Pall>xeieaE ci тки ar oelamenl rs z daener^X: O^i flia n ie F:cл
1964:26-17. '
5asa JDM. Ffi k J i>gmenl ealhNel i p au'ic- k'itia l ret; laser Diotesagualice. An J
[tflhUma I9&i&:70£-1
301 I'fih ET.3jiifila !A Desra И к км гк-del г e^eimenlsl £fcraca i юдаси ап:лзг ii tie
■srt.Aroh Охтакга. '939:13':2t4-9.
302 Э В en ^A Ogden H Fwn Sj. 5uuiei cal йчссртИ&жоиЬ^д a m model or sJaetiiU
ttiva: j.!a:':a: cn nlhei^jti: Ftelnal5Gl 112^4-1
303 'лита U Oiotj ca escraseJa'Eilix . nmerta' anJ clntai t o .fea Sc; Ctmtilmcl
in199l:S6f11*HWL
30i ZibZ-RGcfl'digTfi.ScrcemeR.eLal Eipenmmal dibneflnsi im flsniaralior httieraatal.
SfaejH A'ci Cln la OphlTalmcl 1965:2^ 237-E2
303 Zx j-R Gcodagm fi. Scnenle N, el al. Maiptotooic с ш ^ т cn: al 'el па репч it epd'e -i
Dfdneral>:fl этйпйщ ивп&пг n te rahal ^elna 13ЕЭ;9[31Эг27.
306 З е ™ Ш 5uаезгй oeaasa.la zalic^i г aenle rdcila otecsieralien. Am J OxiTmre
1964:97:'43-7.
307 3lair ll. oflocraph сгйц ^с! he retii]l igmenl ealheliLin: a marrleaiilix al seoile rraaitr
■Jerja-eralH!. to O p ita h o l l975:£2:l9-25.
Э03. Згеае1SB BresifertiM. n e Sl.elal Ш ив! :ajMorchx>Jal ТспакиЬп'^тЬ'апеа
ч mil tfl iweal arascJsr гхч rt aenle macJa degeTerabx. Am J Ganta nml
1962:91:37-El
309 iteH lr SB Brassier Г.М. Hie $L. et al. Sublouea пюшеи ar п:етзгагк г ззпа macJa 1
-JegEreralc-n; lEtUjaiEhibet^Ben пкч^гале £зч xdwsusl p'M'cas. ^slna 1963:3: r- ll.
31u 5ha cra SR Gifpajda] IS Friearai E. ecal. Naijrai hгщ ^ cisalffm Jeceierafta': c! ne
macJa.^ir J CphtttdmcJ 1.&74 73 379-62.
311 Sfecar 1.3rd AC. [JiisTcIm IH Sen le dalami тасайгCKenefiai ii oe Eettftd e\t. 3r J
ap *n d iaT 7 jei:H i-7 .
312 -\iia i jG. Li ierfie с AM, rems ll FL e; al. Senle :'iaa.la degaemlc^: a caK-Eoilrcl si fit.
AmJEpidembl l993:llS:2'3-27.
313 Oiir. ML. JJG3C- FA. Щl^e FE. Sfw# leamea cl d"Cfliidal гючакиar летзгаге n age-
-ealed na:utif c ^ e m l on. CpIdTaJmctaj1' 939Ж:14' 6-21.
31- 5mсJf if.. Fi e £L. Pi-jcnascЙ pal ems .lili Li aiaal тки ar cnien. CtJlhalmaKy
l964:&-:27l-7.
313 iHmira i ER F ne 5. rtlis к The secx<] pre cf pa: exs htt senle matJsr аесетепзьх.
to ^ ilM m til I Й&3: ' 01:1191-3.
316 \lard?f -F. M c o i CM. H. Skm IT raw У a ir final TemaKiilinial cn л age-re alri
ma:iar аесетёгайх-. OXiflaira ogf 1sfl&:£6:1 Ш
3i7. Wi lejsar J' D. AatBl 'M. Stile macu ar csjensfj.?л and geaaiffa а м ф cJ ihe ra id
pgniert ep lhe и ч E( J CpTtafc-jcl 1979:52:E&' -3.
315. WtoiaRktetim ПВ1ЕГ.1 cl ie u t cjsrirHTi tejgJa 1rtfмер* ОатТап'ск^ lSTSjtK
1E50-8L
319. b'dAC,"sahrenofpm ^niepiiieka celacvieMsinТя ddefyTrarsCphlhaJKBl Ek HZ
19Ш 5 73-Б.
330. EfcLnilej: F,A Gass JDK-isota celich nerls cl ihe lesn:; pgrn-a t ep Ihejim 1■k I^ Ie wtfi
wife iracubr & е ж AmJ Ophinal’icJ 137&:6£.:662-^C.
321. He FC траш ш 1Еай| F.P'uecrK. PhotDooagisth^i of sercu; deodmerrts :те retral
pgmat ej) the ir\ in aabenls with seale naafcr cceae. tom OphtHlmd 19S4.' 6.213-Й.
323. Momecs 31jc?/ Graij . Retial jgmerl ealhelel detachments ;n lhe eks'h-: a
anri'c led tra cl agon User рЬпйкндJat cn. S' J Срмтапю! 1Sfi2:661-13.
323. Taitaifee i t Tieanfierl al lelna ригечееейека rfsartinent. АтОр^Йтакге!
№ ;1 5 Ш .
32^. 'jetileeg- i^ies NT ce Jang 3Ш E ii PJM. el a. A'qar. lass -ypij' eni ер^те)a
detaxjrersarje n1siBfrinal newasaJa 'Mrtrones n Ju iisM in ftseile CBCiFam
mace ar cs ensans' а p'aipectK. mfJifliized Gmefies Arch ■:in i c Cphnand
1ВД1Й 71^4
32E. ChaiiDeflr JA, Bnedsr ИЛ BesslerSB.ela.'lbeifiecTlundLsXclxraphsaTd-itfrescen
arqioqmnii 11 Те deifi Псавд arc irealmenl si tfuiridd newascuariiutn i the ЧасJa r
Ptotocoegdadffli Suit. Cphrth^Jпк4с«j,' 198Ш 1 526-34.
336. Ei cl НС. гсЬ JC. Sm eateje iron lie ■,?.■№pijns l. ep the 1j i \vm h age-retled
macuir CtMnsanXi Fjelra 1SSO.' CiJ^a-EC.
327. SgperlW.ElffSdef й.Аега'ие1J el a;. Jilile d tkid a pre.-tuifr uTeiC'Cealijfl'eiK
archxrsphc indng r.cm ittliejj^ fcn iaanasraalSjV A lh ш и а 1dHEHatHLtocii
Gxufania 1991109:211-5.
333. Meredh ТА. B'a ey Ff. Aate-т]1H. tatoiai history d serous defitfmHis у Те lelrci pigrafl
sit'd uni. An J tixtha 1ГС'' 979:45:Ё43-51.
329. Fa ■чг Li. Эк ft. Eirceis C. et al M a d ■;^cny cl relit! 3P ^erl ealheiel detadimerJs m
же-е aled iraaila degae'ai on. GfhhalTOtai' l933:33:E43-5l.
330. ^qemariLJ Э осИ йт JH Nur^nzl if Янг/cl aitljtfil agmecl ealhadtsla^mials
хйш е(1ч№ яМ мБа1а JTrienlra^ecflnrada nethia;a.lirzalicfl Dompkatiig ас^-чеа1и
шасиа'СЕС^пакгг, &s(iKtoch Oil Eo ^lldnoDi 1Й&&22(7:И1-г.
331. Enl A^ if f Fl'docasjgualicfl у ctealcT macu ar Is cits *&. k^pten a;er & _
0Di4haiTS' 079j63SES-73.
332. Macu a1Ft;atxsgjal cn GiUip. чёJ]l -х ^жс iier lass эх1:>:саси1г!вп lcp
ablj^a: re'jjcacu alalia -ж ста ay to лсе-е aled та с ш dagerfal сп'Т'й iT na’ca cl
n l al letn iis a^d in ha acu tv. Arch ОэтТл ircl 1995;l 12:4&(Н1.
333. EicffirrNM.firlieilieL'O.irresi Jj.el a Fs^a pomiFtepiTetd (jkt: ihncn^T Ihe гли
йтт ргсягд ^ с! -jMd и jal асJh'. Aich O^Jha ira ' 990:103:1 EM-7.
33^. Oanrll -L, Ftirav F^;. <ictlctf-ViH. R ps in +e pcmen: ep He in Arch ■Sptilhiimsi
Ш 1С Ц m 4
335. Chuarq EL EircAJC Т'К Ы ш Ш ус! leasff T^ iclrilp+j'^Mepl'Bliim.El'J 3jphlhdnEi
1ЭВ&.72 91 fi—50.
336. Oascsa i Iberic. F. jxtiane G. The tjetesr tfa'acte'iilics cl p(jmert ep the iii 3etaJ irexa:
a mat ci JO е^ .А тг OphltHTKl f3“ ;:lCfel037-J3
337. Ded^fWSaitomG£.IMIwM,e(aI RetiialagifterlealhelialWL's ОртТ^к^кЛ)'
lSfiiSO 307-12
333. Gaa .DM. Pslhac^nes s of teir: al he reliul lianenl ял11й cn'. 3r J iJlham U
12ЙШ313-Я'
339. Green 5N KU'iai U. Acs.i toar у te relira pipnem epnel lit. Renit 1333:3:1 Ё-20
34i], It id 'Hi. IrtadTems Я.э ш е т ep ii"fi t repzi' Gia^ei Ar^ C3h E»p 0 ? lha n1-:'
199£23ttar-1CD
341. Ней; г A. Eid flC. К. Te?j i al recinil ^cniert ep Ihe hni bi. 0?fhdШ
342. le D. YtimLzzi J . Epait 4F. el ь. 1.1и в^ в Л the 'e! na pmreifi epdfilum. А/-ШOjflha mn
Ш Ш 14^3-9
343. Ksenic F. ixtiane G. ^aas G. de I'ealheiur pcirtnnrs apiH ptiamcagJal с i
fc coirs de la degeneiaienK тйслате I ее a i'iffl. J Fir шгй1'1с1 195J.12:773-33.
344. t.fechs'e R Henal Л1.fie^nii pgma l ep ihe □ lesia h 'ic h lie iftiea v^lh a^erra! cn ■у
ixd >sjal ae.r- :. Af^ 0]flha no ' M l .139:1 ^£2-3.
343. NesiKFe M , Hihltt & in Ш E ^ ^ m e n tH B age-re aJ&d chaigea #a>C^-regcfl. Cut
Exeftes 1Мт;е..:2г 1-21.
346. Ed'ffippiH j LhiangE.BidAC.llBriirffiellM He^aia FDErtihLniais^ elna
aqmalepiheia lesra.AnJ ^chlhamii 1®й 103:й53-3.
347. Bf,ai3Gi D: KalniRi GjiakiV. Tea's cl insra'd ngrna r eathenLii1. cajien:£ nielral
daathireiu ай а ^зг ctelial sea:. Relna l S&41 115-6.
348. hamar £F: F.lacJuadunaKC, jcleyAJ.el a Fjelca сигешерейа tea Ш н ге
гйаиина! Ье?дс zinvii ler CHCtdJl neoffiscular iiema dje toice-u also iraciibr
dajeieiallfX. 3rd ftrthdhin 2tX'791S77-8
Ш G:f±oj": 'tl. rrtd 33: к. A ibwppeckIwoo Efl-tisnemara'? atitherana rcmeic
Ephejum.Sf d Sphlhdmrt 1£e5.6C:l7-2&.
330. ifeo JK MsrojSiS fAich: FJ1: Fielna pt:i enl epiTela toi;:: рлеп^^а а'зегк!;.
0]С1Ьа[гоед1ЁМ:уЬ.8-13.
331. Gass .DM. RdccI -aMricfelral тейз: з s (jn ~ycModal leftascLlinzai cn. Arch Oxtha пч
IS3V9910П6НЁ
332. £d"jt; H fltikmaJd H^, .c i sx FN. ngme7 ea ihe e la cs asacoaiec Hth re;ni
pgnist ep lhe \H-deta^irtт m ntacJar rtete ■flafer- Qtftia (гок}^ 1S9C;9f В38-И.
333. Edn etl GR Fi-.d^ Boci CF,el a. Fjracs jngBsflcclnisaiJaniHne n palEtevrth
ELhnelna henc^ce.ton d Ophthalnlof 1900109J3-7.
334. HasfiJtihг. A£. TiHrpe CL el si. ^изесий Ьагскгадег глорпс aoe-ieialed iraatar
d e c la im Amd O^Tilro; 198Э;ШЛЗв-Ф1.
353. Егзсчге UA, Rj : F£. Wassffe зрапатеаJt icbien nsl Ьетсглше Air J Ctnih5Jm-:^
197880S3C-7
35S. Tan Ft,'. Зигогег H. fi:telsc-n Ш Massr^e '.ilreojs Teir-aThige and » 'i e m ja r Iraida;
d£tenef.L'ia-L Алп^ Cpinalncl l9BG:9C.653-33.
357. Greer HR, Gass ДШ Senle dscfinr decenefiha': cl Ihe iraaila. ieinal irJena 12ЛТ. cJ
ihe ■ticu; pagje cencflihated ctnicalr/ aid hsncpDTc^icatfi Ajci Optithatnd 1F ' :&£.
4S7-9^.
353. Jaw A£. Am a MF. Trefrpt CL. ei a. Cha'a Cai nec-^ascJaisili-ar г-Чатreves ^ f aiers
ftih aitanced &enis macJa' deceieiaban: icfe cl Saar phaioaaaJain Arch МчЬаша
1ЯЯЯ01:1% 7
353. L^Jtn kl| E ae i B. Gregj L . ^тпшетн ci -Jscrai'i h Jftile-a age-reimed ш Ja 1
decenerdia - bt J O tT ifrc '991:75:133-G.
3&Э. Bar CJ. Aiflic TH r.'aiane suiecinil &-:jcialic-n i3K>^aed Vi in sen le naaiar 'dega eralicii.
V J^ Ih a m a i 197 71:539^
351. й'гой AC. Cuke JR. Cacto s скеаае.' FsriEW cl Ihe ireiato e. ascnElc 0lena Jn a l
Ытл. and plsms I pd siJtfes. B1J Cphlldina l Э6С47 335-4' 2.
352. Si маVE. B'ciT iril FJ. Heranijpic deto^чгет cf the знатен:! геж ; :•cma Lep lhehn
ArdiO^thatnc '97е^.12ЙЕг-5}3.
353. Fe:n SR. Katz LЛ Ai>3sdxper dJ. el Acule ang e-ctafe дйсяиа тат sacfllx-ean
masifje tenrnhapic ntirp ar cfo^ca detadmem: in upntied dacuoilic aid the'aaeul с
ааргл^. D3i 4halir-ai&^ l9SC:9T70-54
35J. Gass XM. Slefecsc-Dcc a; as cl m aia: diseases: екдпх с and teamed. 2rd ed £t Lcuc:
WWaiw, '977. p. aE.
355. F.jcs F^ 'eie W Стспаеспа jm c ifi uasctiaralfcn cl s n e maii e h p a^etf
hinkA Arch :&\Ш Я 19B21Й.1452-603.
355. Msaite:.Vk 1AK. Eexriphc a rx fi c! Ihe reht]l aamert Mtlhsiui:. Adi _ Gp^alncl
l^ e 102Й21-3 '
357. Ecial: H MdhmaJd HR Almane :ia ilif degei'eiakfl: 'ale d spiead cTдмдгарп с эйюрЛц
aid мя,а № . :jpfclt$ntiacy 19&9:£6:' 041-51.
355. Hclz ^.WfclienstagifTJ FlgjelB elil.BlasfjlKHcJar d'UieTinice-Tsalediraatar
detenifilia': crcgxis and re< lu^cra Cptialratofly' 99^ 1Jl :l E22-3
359. Kla ^IL Ma iin Ш Э с и и к vL: Herecrf и с эре- оaled ■ •'nxlis 'tq s sruitfi:
aasei-:a!cns f nrancaygctc Глчи Arch 1904112^32-r.
370. K)en ZsasC. Qiert d el а. С втф ^nl lactaf HpoMnwphan in эое-'е aleo iraalir
deceitJilia-i £H&Tce2'135:3C&5S3-9.
371. Han& JL HiLScr MA Sci";dl \ et a, Ccaip encei'l larter H-*s jnl rsecaes U'e nsk d &pe-
rebtod tec Jar degeieiatiGr. StiErce 2iI05;jM:-1 -9-21.
372. EJi^if-dsA^' FLlle-'llR.as Kd.elai Осп реш аШ ш Н aotymijXiyr aidage reiilted
ica^ibr cepenaaici St ens 2KE:2&3 -21 --I
373. Tcn^ j » J.2harg'i'.el A. _CdB77l Е-ИТЧА' я к р о р я р Ь а тв э я! ascepiialkte aa-
rettod tec.1st degeieialfx: A -uG£ r^iewicd |ri»arflteis.M il№ 2СЮ,'31955-&'
3:4. Ma ti Fhimifeita 1 Del Я e: al. ra iip ty a l iartar - aid L0C3S77lo 'репе
pDlhira'pia'fi c a Gree< pmdiicr. wlh ioe-'siated im ifcr degene'al ci. Giaeies ft-:f Q r
Eip^thdm d 2009^47:1547-53.
375. [leanpeii Ш J F Acams 3. et al.Ale es ii Te HiA. serine ptpddsse:' с^те a tor lhe 'Rk of
пачаа Jsr age-'e aled naa.& degeieralicn. Cfhli^ioiacv 2>B3:11Eil 200-121 Ej:e7
375. L^aef К EajedEH.RcTCiflF.el a. FLEK-A 10^&7713-НТчА' fc^-jciphism; a i
encilife ape-reiiied к й с л а г cec^neriha' ii "ie r e ch aqi j a: cn. Mcl 'M j C07: ' 3 2153-9
377. Кет* N.H:ijca3.l3iL4ishiK.el a. _CH3Ei77l Е+ИЧЛ' леатз r p^pjfflai J jciccj
icscjspalh/ am ape-refctodr'ficuiaf аедетеги^ r a Japarflse рорииИоп.Ат J Oxihairc.
2C07.1^:5C«-12
373. DeWan А. В'а^н; ME- -ch.. ".0 cflTeh: patwfts Щ igs-relsfcc macubi ce-jereranci Сj"
Oar Gere:Ce, 2C07.1722fi-5i '
37-3. Epa-ffif <L ОйЛ: LM, Ari asw 3M. et а- C3 Rl £2G эс+(т >1Хеш releases гёк cl зее-
retiied гас Jar deceierato:. -m Ws Gece:2}3S:l7.'&2i-i.
ЗЙ. MuI ns R: Overa FiA Qar- ^f. el al F Lu n-3 ftilrihла fi n xnan eves rehancs la age-
retied macJa rtegeierafrx. iaEjie Fbe 2007:34.372-^3.
331. Eloe EM. Егал ТА, Rjsse 134. er al Missense 'j^alcns n Te Itubn E gerje aid ape-ietued
ш аслагсипакт N£nglJM^2MM:351:346-53.
352. EhaslryBi. ^U ehx alneA£C4 and пкМвсчреписЬг&чЗ genes n tan I a cndspiMic
aiescJ Efjdalf>eage-reli'jeil -racja- detenefil»'. tt J t t J \4ec 20C4 U:753-r.
333. Allhneis R Fjrlher e^desxe tor an i^actlior cl AfltH ? lets tfth ace-'e aled n'aaiir
dscenerilia.le rto'nKa'Kl^CR&^eflina JiisonLm .Aid tirr Gaisi 23C,C-:67
487-91,
334. De La Pi- MA. G^ №. AJ>x-F>xq £; ir. a. Ara jiqs ol lha ila jina ciseaae ga e lAEC^i,
ape-iettod n aaia -jegeTeialicf. Зр1Шйп>^>^ V39&:l СЁ' i3 l -£.
355. StiineEM ^y^w VantfeiirflfiK el nl.AHc ^nation hABCRajsocotediWiSlaigajii
disease b ird ace-'ealfiCi iasula deqei eialiCfl.Nal janec l995;2£:3St-9.
355. AltkiielsR Shnqne N:.Ench N.el a. .ij^ x cl ne Siniga di iaeais-jeni- ^ ;R -n ace-
retted racJar dege'fircnan. 3 aat? 1997:27T;1S06-?.
357. Ш ш ил OS. Н а ш LE. iciaer AJ. et al Edeid&d прирез r the canpiaTenl laclDf H
Щ . and 0Frl--e alec |рЖ^| 1эгч^ cf geies agaiisl ареч al&d nacua degajeialcn:
JaiacTenjaiai. etiric diilnanx- and BwUkray meaScat cns. At Mbd 2МЁ:ЗЙ:К(2-534.
355. Н]дя"ш; GS. Arderan CH Jofnsci LV. et ai A ccmmx hapJa^ae г ts ccmaerarl
regj ativ ga'je iacla1h -If''.'-uF! pied sptse; iK^iaas to ape-ietito-d m a la *дечегс1с-п.
Frct'iintosdSc USA £)C£:lC&7227-32.
ЗИ. Cru c<sh<iite K J.'. e R Wan 3E<. 3xl gh; a c аре-realed : iaa.li. Jegxeiancfl. lh: Веа^е1
Dar e?ieihrty A:cri OptrfiiaJmol 19&3: "' 314-2.
399. Ганкг HF. Mura Б. ilfcsl i. el a-, toa e 1/ : and ts- cl ace-e aled iraaj^r degercal cn.
Tracs.Air OpKl'iikiclScc 199С:Й&'.63-^Й.
331. Taitf HF: '7/es: S. № nn Ё. el a. Т а cna-tonr eliecls cl ffite Ichl xi Тй Area
OpThanci 1992:11C:fl9-1Q4.
Э5£. : ас-MOM Равидив с иегз ■
:Аадпр н и ш degas'alai О^ФатЯм^1l935:i2S2Й-^
395. та 1 Могли С. 'to Н Sunl^T and а :е г й а к п и с ш йвдепвайй t o n GHithdmd
1ящшепн.
394. We£ SV Ftoaerlha Fi. B'esstor Щ s al. Bfosue to: j'l cn xc olier гл- teterc й age-
гйа1а ггэсиЬго&репяэ^ toh ^Iham d 1969107:375-9.
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3S6 '^inp RW. Ьс-tar ratton and где-гйай; ткийг c&penerэпт Eurv ^llham i
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re s. la deflenerflHi. Arch ОртгЬш 1333:111:' №H).
396. The Dc-aa Gase-^a Shift Grip Fisk focfcisft? newasoix i«-'e-aled macular
(toenratcn. ton Oxlha no ' 992:110:1701-S.
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fimicipatpf to 3n>D*;-rq. ft". J Ejtfmiai 1£93' 37130-2ВД
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Mtli ке-е aled naaJa -Jeiixeralcnand rleranxG wtti APM££ ccмтпмнгс. instil
орЬййпйИЕйатдатз-а.
401. Jampcl LM. лсе1етз cn aid чс.Ы лейте n Ihe macula Xulxaajbtnix st'.c-. ton
G p h № 1КГ:109:7в9^01
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arlcaagu anls. И Erg J Wen l £&&313:112E-.1
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canpicaied bo :Jia'aca пеошявшайвп. ^ Ih a m a ^ 1ЭВЁ:й6;&5£!-3.
4C6. S hefslaie EuL Laida. L. Bason С. й al. iix dig cofper insalBlisTn л pija wtfc sen le
maala degeTeralia:. A t Орттагии l995;17:4' 9-22.
■Ш6. Tsaig 'JCK. с F t. Sniia- F J, el a. ?^els cl атласам a-a аре-гаше-dnaala
«pare-al cn. D « 0лтапо! 1992:51:ЗЙM f ll
■107. Mfflcnme ih-.ati M, L&a e IJC. el а Мзси ar серела n a i ard afcjded is u n
ce'u tn aitrr. i'tfes: ^ h ljlic l 'it £c ' MG:27:1 Е7&-Й.
K-efl к to i BE*, Fringe Г. Tте reiafanihii d ta i? j® ^ lir tfceaie агй ils nsk lacier tc
agerelEfEC macufipiiri'.Thetei'.troini 1933:100:4C6-14:
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naa.1a igeierslicn. Dptohanflxy 1033:1 CGI &39-13.
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dege™aiin.OptTlii№kiQV 'Эй.ЭйлС'Н
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reiafcc m^itir зг ст. CpTTafcTcfcgy Й193Й02-7
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433 G. Зшсгапе G. "he s f e ff ra fnplii and x sn арсr- taer ca ne fCh'eil rep or a
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гее- 'йа1ес maacr cegene'al с 1aid л(Ше:а елгаЫеа! chxjdil iahasa.la aicn. Ar-di
ifilh^1993.11l:lieS-99.
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e&xg cl ape relaied riaa.la degeieralcn: us3al&d; r>j ngs irem t«i dnica Inals. Ajici
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1973:77:!DPGB—73.
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523. Faia' D. The reiain cf ainad streak to s/sla1^ dssaa Hpiicfiad. H: Cxdss С baras;
1972.
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E&1. Mann 3J F tK tt MA Ттзг JN. f^a та p'ssslie h-£toce:nai.fl a;d '■
’ xd a dae^e tf Ьоте^
GflmMigy?9e63ia&7-«12.
E56. Clarion .G. Psgsc s disae and arci a a et-s iKs : Cue tfmpdarm less/?. B' J ^Hldma
1991;ISSE1
E6t Ca^s 'R &cd! t f ir ? ^ чв al arc^d alreate and dhef xuur i>](rclsb]ri cf FapeLi
dseasa albcne.BrJ Qptilldmtf 1Ш 4 £ га- В £
E6г. frlli &.-. Srqe PL Nuaear n>ajacni n Pagefa d ie a i al toe. Scienx I s-гб №:?31 -1
E5&. Smlh I ^ifll's d a a it ird a^ichd s l'e ^ Ox aorp talic^ 1ен;. E^d 0juta n:&
1ЭЭа^4:Б77-^.
Ей. fenvH An-j&a иаКз зс aslale dafenrais. TrifD Д”: Cm hai'd Soc 1s34.S£j»5-y3.
E№. Erklfi 'f. К'эте! GEi Shi~ab iM. el а. ф а nejapallr/ r Rsj l i <пкак. Am J OtltiajnK
19W;S7:ED6-HI.
E6'. Rasten S-. Lnraslai AL. i^ i F. ftltixenaa a ard inaiMeireie c\ Fapet': сгзэм у 1лпг
LaTcel ММ:37?.1ь5-Е2.
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№дл; pot em: a ta s icpal. Hum 3otal ?i:03:31 :l E£r-31.
E6£ Geiebefg S. Затм !: iL. Dortran -C. el ti. Ea'xn an a Traisficirfllicn nl t e nftat in a pat en!
w. (Г F a il'; daease. Cftt'clmctey SJM .l 37:14Ы-7.
E£4. CcrfflmPL Efjeat GR to tr I nd ng; ii hem xtin SC daeaie n Ja ira ti AmJ CpTtUrd
1SH;74:9t?l-3f.
E6&. Cmixi P, Ee'jeaf CR O ilar' nd ngs n hjam^jccui e k I атетй ii Ja'iaica.Air d
optith*nd 1Ж ^гааз-4а
E66. С и чт P: Ёетат CR fe ls; nnd пз; n efierth aaesof ImuqhiLE aicHi-KlI (кегм n
Januica. Br J Cf hlhdma l 361 -A. '
567. Ceл ^ п Аг Клгаз В. Argcn bier iralnffir' n connpf csdat: у onp с с Етгеакз. ft"i J
C fhiym ai& 7aS 12-17.
E6&. GezfifilsrtJ.GiHf1\D ll.ATCiad itrea^andiickls tsjldseaiAjn J Cphl'Elmcf
Ш :4& 4Б(Н {).
E№. Cdodnai С. kx. Edm xr L. Haiand Mfi. Oilsr vmfeilalcfl; gI if^e cai lieaae Arc.'
OptitfEknd 1 *7 ;Б 0 № В г
E70. Hxilx4!A>d.Pcpi :M. Cantn FI eii.A tn d slreaiin .an a'an xiilefils vjiin Ihihebo us
a ale cdl dseisi E^J Сртга1"й11931 ' -7.
Б7'. dampcl LM, fi Eaaa Jr Ru з: al ЕВДНсйпл cf Brrh'a membrane n ong aid атака
•нm to 'cr^ x s s c^Ji cdTdiesi Arci Cf hlhifmcf 1[1Й7. ■fc 93-E.
E72. Najfll КС, Asdiflai C. ofltta jti )' £ al. ^jgicid sl'esK; aid acJJe fiaemo^fiinGpatn es, 3r
joa-man'fi i m k S M
&7i Pifcn iA n ia J strals r. stiie s i атетс. a 'txf. cf b'lH-aEei.AicfiCtlKhalmcl
шдав&пв.
E7^. iilh g JS.Ela^i FK Prcgn-Daa ai>dПегапч slirgcicsl'ieil:;. 'la sCchlhilma £x UK
19?Ш301гЯ.
E70 AessaxsA. 'rtKfaraj L Ka^xtis E. et al оа Егеай г dSfe-talassaria. An-J
Cfhlfdmai № 7 6 9 9 - 9 2
&7в Cacbagfif ^ha^sS.Ajtaca I CpntalnalMC m ii'rtalilixicfadJe oel ttiaasxme.
М Ц ВД Ш 1Ш ЙЗЗД.
F .-. CiH5 LS. Ai'acc атяо m « I (nr Гетс^И пэритгу. Am J J^fiMmd 19^:77.^ЁН
E76l Ca,fia'jne,i(U^.C'CJarli,riTos n a case of haarragaan Haiseaas. Er J Oxibaira.
E7BL АеаярвДаапйЕквД Sauite R a atftflfjfoj'aiate n hxraigxi Kia mlaaeiiia.
A m Jp tB h n l 1959:1 Ea:3E6-3.
Ей) S i gsma- L . Алра с йгэка г ll^ assa^ tй и . В- J Cfhlhaioa 1SfiSS^l? 5Й.
Ей1 <jrala rf Mxfl?f Ш Afgci'd adeiks n bela Tatassamti rnrcr Br J Cpbha^tf
Ш .7 2 3 0 3 Ч
K2 ^CtTel Ef.P>^[ FC. O LcjJln t.ecsl АгдаййГЕак; г .Tabiiifima т г с E l.
ЦзМ1йЫТ!В1:7Е]Ш
663 Atsscpx A FtuJas СЁ. Ы M, i al L-Ж; cr ^ a i л£зос aled win ^ c i j al'eiks n tela-
tHlassaiiainlffmeda I4 J -eni£]cJ2tt)e:l!7.3&-3.
66^ нахпз E. M at usi.cha;a <£ hJe^isc-rr R si il. В inaress Ле n anja с slraaka n xn-janaJ
J/ssr>ttircfrifla апэста . Ef. KiemscJ 3S^66
£65 iU x ffirJ.'A h is M C rn iln a m L .s a l ArgfijdsTsaksassaciaiHl'NrtabslatD'Xtcljenemii.
AmCpfittEfmcf. 1ВД1:-73-9.
666 UsnscwAn, S^etis J4. An e-z-iBi1Jr el a. M aJa1ахепзаия' n ang aid cnrsJc.
д а т а м и -S6l9::3E-4l
ES7 ^utcc F. MUIer DFP. MsA lasr J. й al. От м1этт i suDpte^jenl: an p'f^ei t fct -e1гapdty
d a w p in d E ra E il^ & J Cp-i!nl"d 19B&:7&'6&-71
666 jw an jal'/ EcXckfil SS. Havercff EE Aigfiic sieala г pailiTh- luntx sxth Msd J
1972,7:.-29S-2E£.
639 A/a11KJ. Fam I al pfifjVesti ax! anja с slrate n Ш ccUa Ixaus. Дт j Сртга1чс1
1977:SS'23-E.
camxra t cl lhe SiLr-pe-rt'eLflr sfxJ'ifre. Adi O tta rrc 1970:H:E2&-31.
691 AJi^^'a-ia H£, jilons A. Une CM, at al Алдлй s=irate '^rt. tDrca'i^ ^раЛ'з cl lbe
elna рсгге7«рг1е1ит:ап£Ы'Л1йха'ата1авП':йпя7 Ел л r>J-2032;15:Ё45-6
692 liraiKJlafe. MaKfrn Ц ^ке A tl a. jser (r-almxt al тгсиа' xtrcli'al re?ш :и arizaaia
n axadilreatf OpThriGlcgG l93::lSE.£4-7.
693 jeisfla': 0. -f клкзе F. Deulma' tf. A isnolemi latw-up sluJy of la s ■жсиЫЬ'а' al
xm aaalif nembrnxs mjfgctd slm^'Am j Op^ahc! 19и.1
69i jm I . Buiilef fJil, Mash MJ e al. Laser Шеэгтеп зг спотов nechaixbrzalicn n pmsra
.-■in axiad stream An1JCthi'diiBl 1S&S " G^ l4-23.
695 Masl к 1 ’■йЬпй' К. ^saie E6 or al. Lass 1»йш п n rraajtflitv cf psejoc^aifffima
aasicxi Cai JCphnama 1J76'-32i’H .
69(5 Atiie: P iX ja F tl а. ^ а и х & з^ х зи jm 1as пйпяазйшк EOUHfifniens
mx Jajea sj^fliinl aj c x fi des sines a'CBtdes J Fr Cfhnamol 1929' £.667—Ё.
ilrea«s.tel] a19&':' 75-03.
693 fttensai CF. SlirutiUC'T si iu jK id ш п зц М ай м . Ar, J Oxlt;a rm!' 976 81:1C4-6.
699 Mrra j : G. Hleti J. Ify eА ос al. htsrrtreal rxiajum i ftу cfcrcidal пеошайпгаЛг m
a gbd al-eifii. Am J QpTTafc-fil 2>Ш] ECi£S2-7'Mi:e'
№ Jd a D. Koiscfi Al, jd a Ж. Я H. ИП'гшез! 'x-ib ZLmik Iralm xl cl micuir cxfctal
imasailaizalcnsKaxaiYlc-aTCiad itrea^a апе-^и 'eiufs -Df a p'csp^clpje сяиау. Reijns
aiGl30fl85-r.
601 Saw M, jcmi F, yxj la.w M. or al Lxg-la m lesuls:(litaiIfeal to x u n ab niefln w
■^lb'ada nec^fiLiasaiicn мхлигг banaajdareaft.AnJ ^Uiam a-КСв 145;53^-
59Й:е2.
602 jfln iiM C M iJS.Ejn Ao?al.hlm*lfoaltaxiSLn:ab ^ о й nl Ix Xc-'a ca
Terr^aaailirial cn г axhadslnea^ a s e i e s . Op'iT-afc'rtfcgicb 3039:223:^-7.
603 Eum13J Hal n EC. lej'clh measiremxls and 1x a s canges -a tfe wx& efe An1J
:^f4hama 197171:42-65.
№ rLCB i. [in « H iJe jthwarae R&^: xi fA/ф . I Axeniei kd i:Ml .5.17' -8l.
605 -amxcfl Gfi. hcnn D. 3rd AC. 'rtsua p'ogrcti: cl d x fcn’i с к о с т я т т пг^зра
Ш 9 0 3 № в.
606 -otfifiia finsSL ^alxlccc т л а э ardспз'эла пхй ес J aisnlcx.AmJ OXTarra
1901.^.77-23.
607 jev\‘ Jti, Faixt НМ СЛ n BJ. The FuJs' axf: Ai ctMtdmciCDfiD and П и ей ег
agcflrapia sij &. At OpTTalxl 1977:S:l 466-43.
&53 Аа(э \1Pa m JU, Jati^E. or al H iira islciv of cxfciaal геэиаси спайаз n Jega'eialr.t
TtfifHi OXI arratm la&f:9l 1573-&"
&39 j ayasafti S. Udiioa M. Selfljs.ia T. Ej.trelral remamaces wh и wtr.xt oachUl
le^asalinial cn г Ш naada -d*patenli n n palhotiio n^tip a. Craslai ATt-:С ii bp
^ Ih a m a is o 225277-60.
6Ю Oiir. №1 G'tec £ Tfa Swlapmert cl tix^ie' xx lta i\ paTiiac ^Глиа Am J CfM'Elmcf
19ЙЙ:’ С6262-Е.
611 ^Tiei ^ V ais Ju. Goniisc Ffi. M jct iс агс« апаз a sfrea<s. and ix ira i с lana n
3iuh e n'emaa e. An J ^pfubama' Й 7 133:537-48
612. rcia!a i.Cphlldmaxiine bilrage E^rir. C.r Eniln: 1Ё62
613 ofeen 'tR ferna n i'. £pa"ta 'th. aihx ^llulm ic piltia a^: x. albi ar>d:окЬо*.
va. % M U Sarriffs: '935.p. 91Щ
6K Cfosin kaj] tf.. ieen Ш. У 'о cgt ivcrgi ш M ltiaaj; црйЬ Яйгз l992;l 2.' 27-33.
615 Зате1 M, Stirciti F. Е.Ли1 cn ipxtanee dj dexlemenl de ia гкье си pae xslenxr a.
т д о Щ J F- oa-lahcf 1391.1*1.6 6-23.
616 Vddahiaih- V. fiiihjrtra A. HcasfcK I ef a. ^nJasral dndibi e::a,^alfi in Ihe ггкиЬ
■dolfl^ed rjj ipedm.Laa-ji' cfllca и^ачй1стхгщ:1ту A£a 0pfl"atvcf^l0:S2.eiT-9'
617 .amxl J.'. 1ицгкй _■.£d"jceda ^ el a Uanxiiic and derapailt cfalsxes, FkI ra
К Ш г1 0 7 Я 1
618 ^etn-n JM. FTuitL Rl. 5maexE of [гак decenaanix and ils refadsr b anJl lexlh r sewne
rn/opia Am J Cpmi]lmcl 19J1:1 r>30-3. '
619 ix ^J. AcIhxj' al гт^эаа h J Cphhai'scf.' 990:74:47-8.
620 4fcr RH Cul n EJ. Laarna '.ivk feasia n paTcfc^ic т^на An' J CfhltafnoDf
197Е.7&Э6-&2.
621 ruiaca U, ctarc T. Solaal Lfiaxe в atpainaM/ niccic monhas. Graslea ft[f! Q r E>r
^ Ih im a 1990 223.174-9 '
622 jlnA E-V ^la JU.TrarpeCL.el a. Hfia'aaa nx^stJaeilicfl гй й д ян ат nrrxia rule
■7\ш Xcf&aiaailaU'X. CffUhamc Euig lS67:'6.72l-E.
 гА ш тае №. ^an ИкЮ юаийитcf co:itrTi macJa leaxa in lhe oculx
hiitKniaimMfi iflid'aroe. Am J OpKtalfll 197^:7E:13-1i.
■Ct. C+iJ: E. PhotoDBgdaiim T-ffilmsi Ld p'ennffi h & d & ric cf&adcraEw. 7^тз An
CfhlMTdSttigTC 70:43:-SO.
70r. Pjii k fine SL. Angx 1аэз [Ьйивд Ы пл n coiar is r^ аягкЕ E}ncram; N OptrEHlmd
ttoJBffiJMS-w:
70S. Pat А t a ■-, fel ы JS. Sore оСягтЭЬха on аах laser rtobcocgu alien Is lie presun'rf
hi^tiMEniEaiffld'STe. ModRcblOptiltiaimd 1tP4:l228fl-!H.
7Ml Satal?: ^ .L « K V' ГегшлЕ+и M&A ranpaolra Etid> al arccn aro lawtanlssa
pnasococcu alien e Те irealn'e t. $ presumed oalx tilts asrrsiis ^vd'anos С^Ша nt tai-
ш рЩ Щ
i ' 0. ScMaticl Jr Tr. Cofieid '1C. 21x* G. el a. PldDQBaJaton arid ctte- Ш эд 1ret hisJaaasmfi
ttorad» ■гхаАпАсааОртаа^Сйкиутп! l955:72:2E&-63.
■ ". RC, jerrirtx F t jgT сиди alia; г presumed hislaDlaamисИэ'дАпе. а лпГ aJed
tin ca Ш , № Ctfiifeimd 1971 36:127-22
711 'rSssurY.ftajE. Eei-Sra l Treatment ff тасизг sub'slna recastliaralMi uhTe
rec-lghi <naAcvi tisenn агезхчес acuarhfiladaamcass^l'Xie.An J ШтНяпй
1ЭВП31:172-€.
7' 3. В.трак №. ОсJa r nамсйа-ЩЕ srrcrane. PplrtHinotogy' 966 93:9&?-3
74. fitte r A FuaicuK MM.Kaplsr Ittdaf.Disseninsieil bisienil ctw jcreli ii s iie й
fteftphara ярвЛаШ i i paaeT wlh 1те ассигж mnrnrieticiatcy imd'aat.
GphltiakTHfcw 1933:32:1'59-34.
715. В а ш AS Кл^ап -J.Cncal aperiHHSMtife ajpcalim ndDl itrtora пидзеиа1
i "йтЬ'Э'ка.зтсггепг paalaperalrareaL-lli. QptlhamiKfl 19S2:S&969-7£.
715. SaE £J Grcsxi'Jaua HE. Lax: FP. el □. Lli'Bilmcrj H lealures ol surgnaft Hcised
3ja?anal aatfscuaf membranes iniie ocular ^:tcpnsirase ^ndorna. ^леп Cfhndn>](
1993;1l1:K-9fr.
7" 7. "batas MA. h£ftsn HJ. SjfgkaJ гепнн! d sufctteal гшавсиЁщ>ал m1те presumed oaJaf
hElnaaEmaas itfd-ame. An J OpiTalrwl 19Jl :l 11:' -7.
71ft; W nd 3E. S to m 3jp til тага^агет of a tonc^sisndiB s iih ta i пвошеи а; п н тгге
я х а и to a^ib hiilDlaanrai. Opntahc S lk 19932A:3£-9.
1' 0. Hmfeia 3£. .Згеза er NM. B'ecils JJ. s al Ritual rai cta л ctseivelfir ftr SLdlneal
cl>xia;l isohaia.^ Л1АП. ener asacc aled wlh lie ocular tels^m os a ^tndione v
■fl tpat^ I OfWiaWc fiidiqs 1щл a ra;dxiiiea eiital licl: Sutmsu or Si.rcer/ Tr afc
jSST' \rnp HШ SST F rn t \t. £. M \ OptfariGl 33W122:1&97-Й11. '
720. fef эег AS. О ог^ M. Ce Fl ere li1,a al £1;Ьш Ja ' н.гсеп/ xf зи твз! Е^лгайа:
rewa^ilarem a aes in palienls члlh sas jtk ! ccuar nisl'DFlsnciib Aiti C^hlhjJn>DJ
тп & ан .
725. Rnq^slt A. P!?T IpTc^d.'timic thniul treatnwaldHiotH nHMEcJaisaftiis С Hi1
aisiiiledvjilh р'е:ипео ocular М зйрш вд synttone pLUifl. ^In to o Aigareiaf
2-310:227:507-9.
721 F t s e i № F j . Saps iijer D.^. E!resaer W>1 e iii. Раой к^тал х Ih s iw v / lh veileftrtin n a^ibr
N iK B ia im a a i: u n s fl'fi lec. jpenlaael 2 ;- a r a: jd^1. С ^ ш п а ^ з с у 2 ( M l 1 1 : ' 72 S -3 3 .
723. EbrlictiЯ , З л а R Ц&1 Fl o l d . n lia d 'e d х л а г и т е с lsr ^creicia r;e'?fiacua,iza ia i
s e a n la y T ' f к и п н ; ocutir ri:tB ]ia im K S i^ d 'a m e . ^e ; га 2-ЗСЙ-:29:' ^ 10 -2 3 .
724. Szfiadj R. S mder Kl. iiah GK. el в. лИемПй bftaajuiiii f(r tTctciSal rеаики aruain in
ct Jsr Патссыг йж. AmJ 0JT a (no. 2п:03:ИЕ:В7Ь-б.
ir£. fesi EE. 5ifc]r MM. \fcrgon;C\1.el sl.Su'gcil remmalffiitoffraim \y dicpafic &t
ctiar nsncFUif'tiii ^voicmeaiactalsGbLLftrieal^a'ada гш а;а!а езйоп:йяя1
P'srerHiK № je £i3*e ^ndJig: Iran Ite rinda"jiM SST Gio-jd H7'hI: SST R=pai fJa 17. A'tf1
0р|Ш2(ШЖ1вЗв-31
M feiiai [ S Fr-lLten Р .Л Ь в Ц el a. nlraaibruraL'Ircm dasaiinilfld istcuain c ie . S ilh
MedJ 1991:fl4:7HD-1
727. GaisJ^W M ceina с с с г к а с ^ п т а к и г г ( а т а & а з й н н ж и с ргемта&зг, £i. л и а C<
f.V % m a l M M S
72S. Janfel HD йстасг-а1 ,йР. Ё. er a. 5ei ra1picrre ic agd ela' hipsn aiii агаеггпе
irrr-i'je jaKitiara rspcrtcl Гнй '^ й . ^eina 19$а:Ё:К£Н2.
7Й1 MiKff j ТА ta?ccrf FH Clamaere s\ a. Massive flrcocufcr hemrntiage г Те ctuia:
riiKBiaimasai^d'aTC.Oonlai'p O D C tarrtFu i l93;i:H-G5.
780. Сэаств Jr \ aae F:T. V lssrr ТА. b.ncfcmiic cbxjlu le^ascjitinia! tn п baUc.Aif
19H;l12:1031-7.
7?.. fiteConsr Ш , Cailgtaa K. Eiss& 1!. ecol. С ntcpanclc^ic cr (be
rmflcle ret л е т ssf'Bingu n&is ralnil jgnerl ealhcicl -iitn^meita imd'aaei ^elna
1934;14:143-52.
731 Рэьа,- Йг ВТ. inow ZN. В* I ilA e! 'A. Ai '.pdae ai гin pie reai 'гт sar-Dcaigu ceas r^i bI
pi^nenl efulh^alcfllachiHilEin Uadi women Fielit КС Ю:13-2й
733. ёГ^йс-п £H L s £С, Oh f t el г1. insdsK ата t n h i агпетг tl р й р гй tfo'a ta
■iasorfcpa^in 'с г а п азйагга Jx ; J CjptilhaliaDi 2Kfc 3 2 5 7 - E l
734. oe h^lc PC. 0'asl 0r Mas -S ecal. Ргй^Игк and epcen tjjgfi bUures d xff i>a3il
^poHlalTiasailopat^ r. Eouiieaile'n 3ra;i. 2037:21.1247.
736. Ctaii R. Vii:;.:j( i - Kant J el i. ^ctraodsl ^'oca^tistJaaalJih a^rdnceTCfctSal
anaslanffiis n JafcnsK pal enl: e ijbe lar picteitfUjric Iherift icf eiu^^e а м - ie ated
;u a lif 'jegeieralicfl. ^ n . О р тГак _й 12 0 3 а ;ЕС :З Ы -а З .
7ЗЬ >каш М, Vto Fl hjr.-sa^.ra A T ie ai ora iy pa oa eicfctial v.asnu tp.il ;,'. Br J
Cphlldnd2CC£i&9m2-7.
737. Hioch. T. Cfcto-ka H. Hicji^i M. el a. [anses j г j3 iel na celanem : h
JaaoiKs; palien!; ^ 's and cto. Rana 2 0 0 3 :? 9 :3 £ & -i^ .
73& Акца Щ Cavies 3f-l l-tnca FE. eL al Ft ipoia: tictctld ■^Kulciiatv and -sti al serau;
ch> ereli-o-Mlln-. Ос1тРи1пв1оду ®СП :13fl:l 009-13.
736l 'Ътиш- L A fieis .i <b, G:+±ojti h" si ai. P-:^p:rdaJ '^a-a oa u s t JDftUtr^ mai^erad пд аз
csna! ie 'oje d w a e t i i B p a ^ C ^lh a m a a j' М Щ Ш 7 :7 Е 7 - 7 7 .
■40. Ciina У Hjnjai М .й к а п ш Ю A el 2 l;lm |in w H 5 u d iztfQ n cd p c (flio « U d K n s H « i c J x a l ^
1е:ст£иу>ззаеста1^]пап оля1-л-тегелсе1а'пс^гарт/. Fieina 2C£*.29:S2-3.
f il Зш а i. d"Kar,a K, lla Vietal Dfienence n i'laaJar ncrff t ogr behveei poJfaida-
■±a;ad3l газавату xa yjiuiksagireiasd Tiacja'decensalia' telsclfc dy &лси
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792. HJrtj^O flrasnlJR ^ ^ H iM ^ an g iig ^ iJli^ lid p E^ ian q tA n ^ C p W tffiliT H l
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rarocan L'aiBiiia^x.A'tf GpThalrtf 1992:110.'717-22.
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acjraoiTi гй^алгЕ дил « ^ т п р п г ^ ,1,:ан! maaarema'Jtd pJsille s<Md 11ж
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This page mtentlonaSly left blank
Folds of the Choroid and Retina
C H O R IO R E T IN A L F O L D S
Any condition causing hi reduction in lhe area of the inner
surface of the sclera (scleral thickening or scleral shrink­
age) w ill cause (he inner portion of the choroid, including
{truth's membrane, lhe overlying retinal pigment epithe-
Eium (R PEJi and the outer relinal layers, Lo be thrown into
a series of folds or wrinkles.1 IndenLotion of the sclera
by sclera] depression or by an orbital tumor in the absence
of scleral thickening or shrinkage does not produce cho­
rioretinal folds. Choroidal thickening by congestion alone
or by choroidal inflammatory or neopiaslic infiltration
may or may not cause chorioretinal folds.1' 15 The terms
"choroidal folds." "choroidal striae," or more accurately,
"chorioretinal folds" are used to refer Lo Lhose folds thal
produce a characteristic ophthalmoscopic, hiomicroscopic,
and fluorescein angiographic appearance in the fundus
(figures 4.Ll I -4.05). figures 4.01К 4.L1JLH and C; and 4.03
IL illustrate diagrammaiieally and pholomicrographically
the histopathologic configuration of these folds.1'1k 16
Acutely acquired chorioretinal folds usually produce
visual dysfunction caused by distortion by the overlying
retina] receptors. Most patients with long-standing idio­
pathic folds, however are typically asymptomalic, have
excellent visual acuity, and may show no evidence of
metamorphopsia on the Amsler grid {Figure 4.01A-D).
Chorioretinal folds produce alternate yellow and dark
streaks, which often involve the posterior pole of the eye
(figure 4.01). Ihese fo]ds may have a horizontal, oblique,
or vertical orientation (figure 4.0]} and are generally
roughly parallel lo each other. ']hey may however, have
an irregular (i'igure 4.0LSJ ) or a radiating pattern (figure
4.04D -f). L'he longer the duration of the folds, the more
prominent they appear. 3iiomicroscopy reveals that the ele­
vated portion- or crest, of the folds appears yellow in con­
trast to Lhe darker appearance of the relative narrow trough
between Lhe folds, 'l’he retina, particularly its outer layers,
may or may not mirror precisely the contours of the cho­
roidal and RPE folds. The reLina in the central macula is
often thrown into a stellate pattern of folds.
Characteristic changes in the background choroidal
fluorescence are caused by folding of (he choroid and
КРЁ (figures 4.dl and 4.Q3-4.G6). I'igure 4.02 depicts
schematically the histopathologic changes occurring in
Lhe КРГ and choroid lhal account for the various angio­
graphic patterns seen in chorioreLinal folds, intensification
4.i>I Idiopa lh i с с hori oreti nal lo Ids,
A—C : Ttiis 49-year-old man has bilateral idiopathic folds (Af.
Не com plained o f difficulty With reading. Visual] acuity was
2(V20 ri^bt eyej 21V25 lefl eye. 1Кг? retriactm] error chanjjed
from -(}. J.1» I о -1-0.75 over 5 yea™ in each eye for din Ian'. e
with a -I-2.25 add rn both еуен. ТЬете wns no d istortion on-
the Am sler Rrid. 5i teieoa nglogja ms show hyperfluorescence
Dorresipor|fl]rg with the yellow elevaled icdcfc [B and C).
I 1 and : E3il.M(:r.il i-■ii■i| i-'i.n- : ■!■I:-. \ l .■i :ц:\\ ■I"-. -.1 ■ -.ч-:
evidence o f die folds as Well <ls evidence ol retina] piemen I
epithelial fibrous melaplnsia and ig e n e ra L ito chat|ge4 Simu­
la Lin^ a n m jd slreaks (arrows, El.
F: Histopalhofoyy of chorioFelinal folds (arrow). Note
p r o life r a te changes and reduplication ol the basemen I
membrane.
G : VcrLic.df' orienled folds.
Irregularly oriented folds.
1 and |: blurred vision occurred in ibis wom an w ilh bilaieral
idiopaIhk folds becaifce qf dew iopm en t ot a ( mMoldal neo-
tosCular membrane in t-he jif^ht eye (arhtrt^ J).
К ant] L: 5enokls m acular detachment occurred in the Lefl дуе
of ihis woman-. An^iof^aphv -Li demonstralud a local leak
bot no definite evid en ce of subrelinal neovascularization.
of the choroidal fluorescence occurs along the crest of (he
choroidal and К PEL folds and produces a series of rela­
tively hyperfluorescent streaks that are evidenL as ea rly as
the arterial phase. The hyperfluorescent streaks are caused
by the relative normality or slight thinness of the RPE on
the crest, the greater thickness of Lhe pool of choroidal
dye benealh Lhe crest, and the shorter course of the inci­
dent blue and reflected ye!low-green light through the RPE
on the cresL compared to that in the trough. 'E'ltis pattern
of fluorescence remains constant, but the degree of fluo­
rescence gradually fades a]ong with (he background fluo­
rescence, usually wilhin I hour The troughs of the folds
appear hypofluorescent. In some cases the choroidal folds
are quite broad and the troughs between them may be nar­
row [fsgures 4.03К and b and 4.0411J. 'Ihis results in the
angiographic finding of narrow dark Jines running within
a background of normal or slightly intensified background
choroidal fluorescence (figures 4.01 f and 4.03К and tj.
indocyanine green angiography also demonstrates (he
Lines; however the hyperfluorescent lines appear to be
broader than they appear on fluorescein angiography. 1!'
 Angiography is helpful in demonstrating these folds.,
which, if only mildly developed, лпау be overlooked. JL
is also helpful in delection of proliferative .and metaplas­
tic 131L changes [figure 4.01 L).. drusen formation, focal
ldJL leaks- and choroidal neovascularization LhaL may
occur occasionally along these folds (Figure 4.0]] and Q j 5
Angiography is also useful tn differentiating folds of
Lhe choroid and &P£ from folds in the relina, xvhich do
nol alter background fluorescence (Hgure 4.061; and E).
Aulofluorescence imaging also demonstrates the chorio­
retinal folds wilh the color of ihe lines being most often
opposite Lo lhe lines seen on angiography 3"he crests
appear dark or hyp о auto fluorescent due to s( retching
of lhe pigmenl epithelium and spread of the K[3L pig­
menl while the troughs appear hyperauto fluorescent due
Lo crowding of Lhe pigmenl tn Lhe pigment epithelium
(I'igure 4.02J and K). Auto fluorescence is rapid and non-
tnvasive and can replace fluorescein angiography. It is
especially useful in monitoring folds that are expected Lo
resolve, such as afler correction of hypotony, resolution of
choroidal detachments, and so forth.
Ultrasonography usually demonstrates some flattening
and thickening of the posterior sclera and choroid Ln (he
area of extensive chorioretinal folding (Figure 4.04ti).j1"'
Alta and Bvrne studied 31 eyes with folds in 24 patients
and found that over 60% had flattening of the posterior
ocular wall, 4Qc/a had thickening of the retinochoroi-
dal layer, and 25% had distended optic nerve she aLbs/"'
Computed tomography of patients wilh idiopathic
acquired folds also reveals flattening of the posterior globe
and mild to moderate enlargement of the optic nerve
s heaths. 11
Causes of Chorioretinal Folds
id io p a th ic C horioretinal Folds
Idiopathic chorioretinal folds are m*>st frequently encoun-
Lered as an incidental finding in predominantly male
patients, who are seen because of presbyopia and who
have normal or near normal visual acuity. these patients
typically have hyperopia that may vary from 1 lo 6 D or
more. When the lolds occur in the macular region, they
are often roughly horizontal in Lheir course or may radiate
4.0l! Chorioretinal folds.
Schematic diagram cornel а I ing the histopathologic a rd fluo­
rescein angiographic changes caused by wrinkling ol (he cho-
rc>LcI and retinal pigment epilhellfim iK fl:.. The y^JltAtf-.coldlfe ir>
eath d iig n ir represents fluorescein dyu in the choroid.
A: N o n n a I re la tio n s h ip c f lh e R F t lo [he c h o ro id ^ H ) a n d
scFera (SC].
B: ilighL w rink ling of Kruch^ membrjflne and Hf'E: lhaL may
produce I ill I с or no change in [he? background chohBmlal
fluorescence.
: M ore marked folding :r> rhe choroid and RF’t. The Kf-nt
on Ihe crest o f ifiE! fofd in relatively thinned LlefL arrow I and
Lransmitt lhe background choroidal flucKEEcence beLLer than
the compressed К HE in Lhe troughs o l (he folds I right arrow:
1 injure 4.0EA-L).
D: ESroad choroidal folds w ilh relatively narrowed [roughs.
There is compression- and heapjnj'-up of Lhe KPL in Lhe
trough ^ri^hs arrow:. The К ГЕ over Ihe center of Lhe folds (nay
be r e la t iv w normal or hh<*w some loss-of pigmentation ilefl
arrrKVj 1-i^ure 4.01 [ J and E).
E: After resql|mtin o f Ihe chojoidal folds, linear lines of
hyperpigmentation (arrowy m ay remain in Lhe region o f Lhe
previous nought and cause dark lines ahgiogfephicialEyi
F and G: A 5S-year-old male with b ilateral idiopathic folds
rind organ LransplanL relinopathy secondary to a renal trans­
plant. Note the orange flecks in [he right eye (arrows). He
underwent focal laser to a leak along lhe ST '.buperoLemporal
a rcade.
H and I: Hluoresoein angiogram а year latefsT^iws allernate
lif^ht and dark lines an:: hvpofluojescence o f Lhe two si Ins of
laser phcHor:oagu3a Li on in the nght eye.
I and K: Increased 8ulofluorescont lines correspond 1o lhe
dark lines on the angiogram in both eyes. The pigmenl epi­
thelial alterations in Lhe fieri papillary region seebndary to Lhe
chronic 1C5<_' idiopathic cefitral serous chorioretinopathy:-.-'
organ transplant retinopathy are seen as Lri radiate Fiypoau-
tofluorescence around an increased aulofluorescent center
Htoposite lo Lhe colors on an angiogram.
ЬЧ—1;, ( m m tj.L-Jb. 'i
outward from the optic disc [E'igure 4.0!J. They may
involve most of the posterior pole of lhe eye. frequently
they are confined lo an area either above or below the
macula and optic disc. In such cases their course is often
irregularly oblique. Iheir distribution in both eyes is
usually symmetric. E ' h may be confined to one eye in
some cases. Acquis ilion of folds in the second eye bpay
occur dnring observation. Idiopathic centra] serous reti­
nopathy occasionally occurs in these patients (i'igure
4.02]:-K; see Chapter 3 for discussion оГ associated find­
ings In [CSC). Since in the embryonic development of the
eye, the choroid should adapt itself lo developing sclera in
such a way lhat folds do not occur and since jnost patients
wilh high hyperopia do not have cEtoriorelinal folds, it
is probable that these folds are a c q u ire d .'"""'' Some
patients experience rather sudden change in vision, sug­
gesting lhat scleral shortening may occur abruptly in some
cases in the absence of any other sigjis of orbital inflam­
matory react ion.'1''1 It is likely that some inflammatory
process affecting the posterior sclera, either in late prena-
Lal Eife or some time during childhood in the absence of
clinical signs or symptoms, causes shrinkage of the fibrous
tunic of the eye:1 This xvould account for the hyperopia.,
the flattening of the posterior sclera, and the folds lhal
remain as a permanent residue of this inflammation.
Retrobulbar M ass Lesio n s
Benign and malignanL orbital tumors, including Eirdbeim-
Chester disease, lymph angioma, hemangioma, orbital
pseudotumor and others, as well as orbital implants for
repair of orbital wall fractures, may cause only an inden­
tation of the globe or in some cases may cause scleral
edema, choroidal congestion, and chorioretinal folds
(bigure 4.0:5Л-С and 4.04 A and :-JV rltie pattern and
Location of these folds may or may not be helpful In defin­
ing the site of the tи то г/'’ Intraconal tumors often induce
hyperopia, and extraconal tumors often induce astigma­
tism, broad yellow chorioretinal folds should be differen­
tiated from the finer retinal folds th.it may occasionally be
produced by a retrobulbar mass, Ihese latter folds produce
no changes in the angiographic picture. ]f the re tro b u lb a r
mass is removed or otherwise treated successfully, the cho­
rioretinal folds usually disappear (figure 4.03A-E'}.::
Scleral Inflam m ation
Thickening and inflammation of the sclera in thyroid
eye disease, inflammatory pseudolumor of the orbit, and
rheumatoid posterior scleritis may cause chorioretinal
folds (]:igure 4.03A-F).
Scleral Buckle
Jluckening of the sclera in the vicinity of a scleral buckle
for a rhegmatogenous retinal detacEiment may occasionally
Secondary chorioretinal folds.
A —C : LhoriortHinal folds caused by a r orbital inflammatory
pseudotumor in а 7G-year-old w om an with blurred vision
and proplosas of lhe rif^bL eye of reconl onset. Note prom i­
nent Ljroad tbnribre^rial folds delinealcd Li\ dark lines sep­
arating Lht? folds 'black arrtjws, A . Nole that .ill Ihe retinal
[olds do nol conespond to tbe fold к in Ibo choroid. Black
arttiW indicates a retinal fold. Fluorescein angiography
shows dark lint's tiirroWs^ B j liuil cor rtispo nd to I ho I roughs of
[ho i boroidal folds. Ten w^elcs after Ireal ment w ilh tvstemic
steroids the visual acuity returned to normal. The proptosis
and lh-E! chorioretinal foldsdisappeared 'Cj.
D —F: Chorioretinal folds and papilledema in a middle-aj^ed
m m a n with severe thyroid wtophlhalmos. bjrni lar changes
were present in the opposite eye. A n ^ io ^ a m i showed dark
lines i arrows, h) corresponding to the troughs between rela­
tively broad choroidal folds. Thw e was some dilation of Ihe
capillaries on lhe optic nt'rve head. Sixteen years later :Fl the
proptosii, chorioretinal folds, and papilledema bad resolved.
G and H : Chorioretinal folds associated with a malignant m el­
anoma ol Lhe choroid superi(H lo the macular region i.arrow.
G|\ In the histopathologic section of choroid (H) laken just
inferior to the melanoma, note configuration of the folding
ot Lht! pigment epithelium, Bfuch'*. membi.ine, and 1he: inner
choroidal 1issue. T h eciesl i ,i f n u w . I li corresponded lo lhe light
lines in C . The choroid Was considerably engorged in this area
adjacent lo the intraocular tumor. There was mild scterilis.
J—L: A 73-year-oEd male with limited suprachoroidal hemor-
rhiif^G during cataract s’jr^crv w illi ved^cally (NienLed folds
[joslerior to a lem pira I choroidal hemorrhage. The angjagrajji
a nr; .luloflu orescence imaging show allurnate dark and light
lines ibnl are opposite in colors lietween the lwo. Churiorclinal
wrinkling ГЁнееп al the retinal pinmerH epi I helium and cb q ra d
on optical coherence tomography; note Ihe elevation o f lhe
с horoid cofTHspgnding lo the choroidal hemorrhage.
C A - C , Ir iim КгЫ 1 . l n r l N r > r 1 (m , '1,
produce chorioretinal folds, which are usually present near
the posterior slope of the buckle.
C horoid al Tumors
Choroidal tumors, particularly malignant meEanomas
and metastatic carcinomas, may produce folds in the cho­
roid and retina surrounding the base of the tumor (i-'igure
4.0j5ti—
1J .1-11 lliese foids are produced by mechanical
displacement of the surrounding choroid by (he expand­
ing tumor, as well as by vascular engorgement, choroidal
edema, and scleral thicken ing.JL
H ypotony
In some instances patients with Intraocular hypotbnyi usu-
□I]y caused by a wound leak. cyclodialysis cleft, or exces­
sive filtration after a glaucoma-filtering procedure, will
develop loss of centra! 4rlsion secondaiy to marked irregu-
Ear faldlng of the choroidr RPE, and retlna.2,s-2ft'J5 Initially,,
these folds are broad and are not sharply delineated. !hey
tend to radiate outward in a branching fashion from the
optic disc temp ora! Iy, whereas nasa! to the disc they tend
to be arranged concentrically or irregularly (Hgure 4 04E-'
and H). This difference in the pattern of the folds Is prob­
ably determined partly by traction exerted nasally by the
optic nerve as the eye moves/0 ihere may be a broad area
of swelling of the choroid surrounding the optic nerve
head, which together with circumpapillary retinal fold­
ing produces a picture simulating marked papilledema.
The sensory retina may be arranged Into irregular folds
that do not exactly parallel the choroidal and RFE folds.
'Jhe sensory retina is often thrown into a series of radiat­
ing or stellate folds around the center of the fovea {Figure
4.04H). litis unusual central stellate retinal wrinkling is
caused by the central displacement of the normally very
thick retina surrounding the Very thin foveola by the thick­
ened posterior scleral wall and engorgement of the cho­
roid. lhe retinal vessels are often tortuous and sometimes
engorged. Cystoid macular edema is not usually present.
Jhe primary cause of loss of visual acuity in most patients
is the marked folding of the reLina cenL rally. Shallowing of
the anterior chamber caused by cilioehoroidal edema and
detachment may occur. A postoperative wound leak or a
cyclodialysis cleft, produced either inadvertently during
an iridectomy at the time of cataract extraction or inten­
tionally for the correction of glaucoma, were formerly the
most important causes of these changes. With the devel­
opment of improved techniques of wound closure and
controlled trabeculectomies the incidence of hypotony
maculopathy decreased dramatically during the I9B0s.
With the introduction of mitomycin С and 5-fluonouracl!
to improve the effectiveness of glaucoma-filtering proce­
dures; however, there has been an increase in Lhe incidence
of hypotony macu[opathy.-M Patients with chronic
hypotony caused by cyclodialysis are at risk of developing
permanent anterior synechiae and intractable glaucoma
after surgical closure of the cyclodialysis cleft, liarly detec­
tion of the characteristic fundoscopic picture of hypotony
and its causes is important because surgical correction of
the cause iviEl usually result in visual improvement. As the
intraocular tension becomes normalized, the choroidal
folds become flattened and may completely disappear. In
cases of prolonged hypotony, however, permanent, irregu-
Early dark, pigmented lines caused by changes in the RPE
4.04 S e c o n d a r y c h o rio re tin a l fo ld ?.
A rind H: Cbnriorelinal folds- cauned by orbilal infi llral ion by
ал eslheSdijff^^urxJbla^ittfna. Stero l a n [Jtq grA'iTiз revealed e v i­
dence of the ft]Iclt in addition to many ba&^l laminnf drusen.
C -E: Radial chorioretinal ['olds caused by c o n !ra tio n o f a
choroidal neovascular membrane (C N V M ) lying beneath an
□Kudative felinal pidmenl epilhelium iKKLl detachment in
a man with age-relaled m acular degwieration. Angiograms
showed lolds and gliotic neovascular membrane and Ef.
F and G: Chorioretinal wrinkling caused by iTyfioLony in a
patient following glaucoma surgery with mitomycin. Note
the mild tortuosity of [he retinal veins. Ultrasonography
showed *ignil"icant flattening of the posterior ocular w all and
congcaled choroid.
H ,ind I: bJadia].. irregular, and horizon fold*. in a palienl
w ilh hypolony. O ptical coherence tomography shows
invokiemont of lhe choroid, R P t, iind phclbreCepmrS in lhe
(olds.
|-L: Kilak'ial ischem ic oplic neuropalhv nf unknown cause
in a ЬО-утеат-old wom an w ilh horizontal cboritHeLinal folds.
DespiLe mlunbjve systemic cortfco^ieroid therapy bilaleial
oplic atrophy occurred anrl visual acuity was reduced Co
20/-t00 1 1 months later (I).
I- . L iir J L i , c x j u r l u s y i l l L J i . k ' r f r t ' y К .н п п и ;г ; H л г к ! 1, M J L i r C n y <jl D r . IV^ l i I
S h r n b e r g , It. I
reEnain. These changes are often present nasally as welt as
in the macular area. Eiarly in the course of hypotony, fluo­
rescein angiography shows an irregular increase in back­
ground choroidal fluorescence corresponding to the crest
of the choroidal folds and also shows some evidence of
leakage of dye from the capillaries on the optic nerve bead
but usually not from the retinal capillaries/ Permanent
alterations in the К PI: may be demonstrable with angiog­
raphy after resumption of normal intraocular pressure and
marked improvement in the degree of chorioretinal wrin­
kling. it is not known why most eyes with the acute devel­
opment of hypotony fail to develop chorloreLinal folds.
The maculopalhy is most likely to occur in young myo­
pic patients. 32 It is possible the sclera In young patients
is more susceptible to swelling and contraction, which
reduce intraocular volume and cause the redundanL folds
of choroid and retina to develop, ihe pattern of the folds
cannot be explained on the basis of uveal edema alone.31
C h o ro id a l Effu sion
Choroidal folds are also seen posterior to choroidal eleva­
tion in patients wilh both serous and hemorrhagic cho­
roidal detachments, lhe rapid rise in choroidal volume
throws the retina and choroid posterior to this Into folds
that run parallel to the elevation (Pigure 4.031-K: see
Chapter 3).
Ch oroida! N eo vascu!anza tion
Contraction of в sub-RPE choroidaE neovascular cotrtplex
and the underlying Bruch's membrane occurring either
spontaneously or afler pholocoagulalion may cause a radi-
.ilirig pattern of ch on ordinal folds around the membrane
(figure 4.04C-H).1111 Contraction of lhe superficial part
of a sub-KPE neovascular complex may produce a series
of parallel hyperpigmenled folds in ihe Щ Е overlying lhe
neovascufcar complex № discussion of occuli choroidal
neovascularization in age-related macular degeneration
tn Chapter 3). Radial chorioretinal folds arc sometimes
seen in association wilh a pigmenl epithelial rip follow­
ing treatmenl with antivascular endothelial growth factor
agents (Hgure 4.04С-Е).'Л
Vogt-Koyanagi-Harada D isease
'Jhe earliesl manifestation of Harada's disease is conges­
tion and Lhickening of the choroid visible as choroidal
folds or slriations^1'■l4-M: followed by exudative retinal
delachmenl. ihese slrialions are usually seen in the less
or later involved fellow eye when Lhe patient presents with
symploms in one eye, and can also be seen further in the
disease course in areas outside the pockets of SRI-' (sub-
retinal fluid). С-scan optical coherence tomography [OCE')
shows these unduLilions on the RE’t layer, which resolve
once lhe retina flattens111" (see Chapter 31 J.
Focal C horioretin al Scars
Occasionally contraction of deep focal chorioretinal scars
from a variety of causes at lhe retinal choroidal interface may
cause a pattern o1' radiating folds. Johnson et al. observed Lhe
development of radiating folds around what they believed
was a scar induced by itie operating microscope.:-
O p tic N erve H ead D isea ses A sso cia te d with
ch o rio re tin a l Folds
]he changes in the posterior sclera responsible for shrink­
age and flattening of the posterior sclera in patients wilh
choriorelinal folds may also be responsible for reduc­
ing the diameter of the perioplic scleraE ring and dura.
]"his change may be responsible for the frequency of lhe
"crowded disc" appearance or pseudopapilledema [i'igure
4.04Л and B) in these patients and for predisposing them
to the development of op Li с disc hyaline bodies (drusen).
4.H"i Choriorelinal foldsr pseudopapilEedema,.
juxtapapillary chorioretinal atrophy, and streaky
hypopigmentation of the retinal pigmenl epithelium
(KPE) peripherally in arteriohepatk syndrome
(Alagilie's syndrome) in a father and two sons.
A - D : Note the long narrow facies o f lhe 45-year-old father,
horizontal t hori ordinal folds (atroSbs; li and D), and slreaky
hypopij>men(;LLion of lhe KHL m the peripheral fundus CO­
E and F: The b-year-old son. Note long fades, psetidopapiri-
(к4б**па, and mild chori ordinal foidb (arrows, Fl.
G-l: The 13-year-old son. Note juxtapapiEiary changes, in Lhe
pigment epi1 helium. r?lL!-val-c?cl nasal dibt d$£argllTS- jand streaky
dep lamentation of Ihe К Kb. A ll lhree hjad л о г та ! visual ж Li­
lly ai;d jiptma} ulec Irnretino^Mms.
I—L: Posterior embyotoxin (aunws, | and K) in a 3 'ft-year-
oid child w ilh Alagille's w h o died Ьусгшыс of con^pJicalions
associated with hepaloocltar tafcifipm a. HlstopjaB^ployiC
ечапиnation litvfeatfed e in o e ite of hyperLrophv of SchwftJbt1^
rltig I a now, K) and patchy areas af variation in Ihe size and
melanin conlcnl of Ihe pigmenl epithelium 'arrows, L>.
i l - L . Mu-. l j s t - vwv- f jf t 'M 'n k ::! b y L V iS ii-O . h -n s c n .:l I h i; : i im b i n e d
V-t: г hi ■:nl- 11 S o c i e t y .. 11 г I h u f e f x f j j t t '. j f^ I , I h . i : m i t : K i i h o k i f t v ' £ o t : i « [ S n i L ' c C m i ; i n
М.ту 199-2. l-гтлп Eitrfciiiy ..'I .:l "'l
juxlapapillaiy subretinal neovascularization- ischemic
oplic neuropathy (E'igure 4.04J-l,)r and papilledema.''4
The small diameter of lhe oplic disc unassociaLed with
chorioretinal folds has been implicated in the palhogen-
esis of pseudopapilledema, ischemic op Lie neuropathy/'"■:u
and hyaline bodies of (he optic nerve head.11
Chorioretinal folds may occur in association Wilh pseu-
dopapillecfema in palienls wilh Alagille's syndrome [arte-
riohepatiс dysplasia] ( E-'igure 4.05; see <]hapter 5J. 1''■''
Chorioretinal folds often showing a horizontal course
in the macula but converging on the nasal side of the optic
disc haw been described in association xvith papilledema
caused by raised intracranial pressure.::ч" 11 ihe mechanism
for how papilledema causes folds that extend well away
from the optic disc is difficult to explain. The fad that
these folds may persist after resolution of papilledema sug­
gests lhal in some cases they may have been present before
the development of lhe papilledema. Because chorioreti­
nal folds occur with such frequency, their association wilh
other diseases m ayor may not be pathogenically related.
R ET IN A L F O L D S
I'oIds lhat in5jftilve only die neurosensory retina should be
differentiated from chorioretinal folds, '['tie)1 may occur in
3 variety of dreams lances and may simulate chorioretinal
folds (figure 4.06). They may be narrow and have a less
striking color than chorioretinal Folds. 'I’hese are seen most
commonly radiating away from a focal area of cotitradion
of the inner retinal surface by an epiretinal membrane (see
Chapter 7) or from an area of contraction of the outer ret­
ina in lhe region of a chorioretinal scar. 'Ihey may occur
concentrically around an 3cutely swollen oplic nerve head,
and they may he seen radiating away from the optic disc
following resolution of inflammatory diseases of the nerve
head and juxlapapillaiy choroid. A radiating pattern of ret­
inal folds centered in the macula occurs in a variety of sit­
uations associated wilh uveal and scleral thickening (e.g.,
[he uveal effusion syndrome), diffuse inflammatory cell
infiltration of the choroid, scleritis, and hypotony (f igure
4.04fl and 3]. Ihese may or may not be associated With
folds in the utiderlying choroid and KI’L [see previous dis­
cussion of chorioretinal Folds}. Irregular, broad, yellowish
folds involving primarily the outer layers of the neurosen-
sory retina are often seen in bullous rhegmatogenous reli-
nat detachments (figure 4.06А]. Prominent retinal folds
extend mg into the macula following surgery for repair
of retina! detachment may be responsible for subnormal
vision. 'Ihese may he caused by posterior placement of
radial scleral buckles, retroretinal fibrous bands (figure
4.0615), and fofds caused by use of inlravitreaf gas (figure
4.0&C).:,J' ']h i& complication is seen most commonly
in patients after pars plana vitrectomy, particularly in
those with subtotal retinal deLachments and either inter­
nal drainage through a peripheral retinal hole or exter­
nal drainage wilh simultaneous gas insufflation (figure
4.06C). Figure illustrates an unusual cause of
Lransiettl radiating retinal folds in a patient with the acute
onset of drug [chlorthalidone (Uygroton))-induced myo-
pja_,i sii,5, д^т лаг horizontal and radial retinal folds have
occurred in the macula of patients with acutely induced
myopia caused by elhoxzoljmide (Cardrase), acelazol-
amide, acetaminophen, and hydrochlorothiazide.''
4J0 6 Retinal folds.
A: Outer rc1ma3 feidiV in a rfw^malojiennus retinal
deLachmenl.
EJ: Prominent retinal fold caused by relrorelEnai fibrous band
'.arrows!' of гпеМрЗль! ic retinal pigment tipilholium (KFFl a11ur
scleral b u ttlin g procedure lor tfoegmatoypnoyp deLachmcnl.
Ketinal fold единое! by pnslunor sliding o f retina after vit-
reelomy ,ind scleral buckling in thi-s palionL. Note Iw o drop-
3oLs of demuonjCarbOrt liquid under the ix?1iг»л temporally.
I. : -F: Hne retinal folds radiating cxitw^md from I ho m acijjai
region LJl in a 22-yenr-old woman w h o developed acute
myopia w hile Inking chlorthalidone 5 daily for 2 weeks,
following delivery o f an infnrrL. Ног uncorrecLed visual acu ­
ity was 20/200. W ilh cyclopleyic refraction ol -4.75 in the
ri^hl eyo her ajHjfty was 20/25, and w ilh - J.? .1! in I ho loft eye
the acuity Wei'S 20^20. Angiography -.Б was normal. The med­
ical ion was stopped, and w ilhin 2-1 hours her Jmcorrected
visual acuity returned to 20.Пз and the retinal folds disap­
peared |Fj. H e r intraocular pressure was normal before and
Lifter cessation ol Iroalmon-L.
G - l: An unu5.uaI concentric pattern of superficial retinaF
folds of unknown cause in a 20-year-old man com plain­
ing ol bilateral loss of vision. His. visual acuity was 6/200 in
both eyes. Л KimilLir patbefn of relinLil to Ids whs present In lhe
other eye. Fluorescein angiography was normal. Neurologic
Examination was unremarkable. fh e eleclroretinoj'Tam w h s
normal. Visual evoked responses w ere subnormal.
r ..\ C o u r t a y o l D r . L1 i i K.l t L f L iIjlk in l.'
In some cases- hoivever. with acute drug-induced myo­
pia, researchers have described no retinal changes.1 ^ 'lhe
presence of transient radial retinal folds in these patients
suggests that the drugs cause sub macular edema that dis­
places the macula anteriorly, which might be expected to
cause transient hyperopia, lhe greater efFect of these drugs,
however, is probably exerted anteriorly, where edema of
lhe ciliary body may result in narrowing of Lhe anterior-
chamber actgle, relaxation of the zonules, and increased
lens curvature.
Figure 4.L16C-E illusLrates an unusual pattern of concen­
tric superficial retinal folds of unknown cause occurring in
both eyes of a heallhy young man.
P O S T E R IO R M JC R O P H T H A L M O S
An elevated рйМШрпию|1аг retln □I fold may occur in both
eyes of patients wilh congenita! foreshortening of lhe pos­
terior ocular segment and a f£la.tively normal anterior seg­
ment (posterior microphthalmos; L’lgure 4.07A-D).'1*■ lhe
eyes are highly hyperopic [usually greater than -f Ю.00 t>),
and the acuity is usually subnormal [20/30-20/400).
ТЬё corneal diameter and the anterior-chamber depth
are within normal Limits, whereas the length of'the globe
from the posterior lens surface to the oplic disc is short­
ened. Ultrasonography can measure this distance, thus
confirming the clinical anomaly. Angiography reveals the
absence of the relina I capillary-free zone due lo crowd­
ing of the retinal elements in die fold ( l:igure 4.07H
and F]. The disorder rmiy be inherited as an autosomal-
recessive trait occurring sporadically and in siblings " 1 '
rm biyologicjlly, the- retina is formed by the neunoeclo-
derm and the mesoderm contribules to the choroid and
the sclera. Since there is an anomalous paucity of lhe
mesoderm in this condition, lhe normntl-size neuroeclo-
derm ейпforms to the shortened mesoderm thus throwing
4.07 Posterior microphthalmos.
A —F: This 22-year-otd Iraqi male had poor vision in bolfi
eves since ctiildhooft His p.uents w ere fllrst uousiпк, Lind he
has oLher sipjfflMfi with ^imilai condiliun. His visual acuity
was- 2&70-2 and 2СУ20С}. He had normal corneal diameters,
short H^xial Itinglh isnd High bypefdpli; H is ftffrfldtipn was
+ 10.75 + i JOfr k 100 righL eye and +12.50 + 2 . DO X 1 70
M l eye. there wore1 typiCaJ-apBfi^rij^g riMStEEnmatLjIar ioklt
in each Ifeye !A- L3 and i i itTrjj/iipluv Showed an absent loveaI
avascular zone it, F).
G and N : С Х Л shows the fold to involve lhe neunosen-
sorv retira alone s|)ari:i}i Lhe pkpnenl epithelial anti phoLo-
rttepLor layers.
|Д-|-£. c u n r t n y (31 Ur. W i l l m n J-. M iu k -г an d Dr. k ' l k V. Okhu.
lhe redundant retina into a fold. Complications include
uveal effusion due to the associated thickened sclera,"
and rarelyr bilateral macular holes."’ lhe condition is seen
worldwide and has no racial predilection/1' ' An О С Г
can easily depict the fold and confirms the involvement of
lhe neurosensoiy retina alone (E'igure 4.07G and H).
JJ(rf&7T£FTMiiTDpbtjfyltnOB 2 33
OUTER RETINAL CORRUGATIONS
IN IUVENILE X-LINKED
RETINOSCHISIS
Jhese * flying s^giill'^pjw ialtng corrugations are seen in
some cases of X-!inked juvenile retinoschisis' fc4Q [ligure
4.OSA. C r and E}). They are seen most often temporal to
the macula, except in one ease where they were present all
around the macula. StraLus O C I has demonstrated these
corrugations to be in lhe outer retina (photoreceptors and
outer plexiform layer} (ligure 4.0&H and FJ; the newer
high-definition О С Г should be able Co delineate these
folds betler. The COmigallQOS can change in orientation
and even disappear (Rguie 4.0ЙС}, hence are speculated
to be caused by tautness of the adjacent retina to changes
in the height of the macular schisis.
NONACCIDENTAL AND
ACCIDENTAL TRAUMA____________
reri macular retinal folds are seen in nonaccidental trauma
(shaken-baby syndrome) and some cases of severe acci­
dental trauma, which result in extensive retinal hemor­
rhages, intracranial bleeds, and sever raised intracranial
pleasures/11 14r '] hough initially attributed solely to non ac­
cidental trauma, these folds are seen at the periphery of a
dome-shaped retinoschisis that involves the macula, lhe
severe rise in intracranial pressure transmits the pressure
through the perineural sheaths resulting in shearing of the
retinal vessels in all layers, causing bleeding and extravasa­
tion of fluid to separate the retinal layers154 (see Chapter 6).
4r08 Outer retinal corrugations.
A—C : Sibling 1: 17-year-old male with rapid change in vtsiun
in both eyes from 20/25 lo 20/50 ri^L eye and 20/70 left
eyfi over 3 months. Both eyes show mam Inr schisis with fine
radiating retinal foEds. Temporal lu lhe rnacuEa are "flying
seagull "-I ike outer retinal corrugations. FluoresceEn angio­
gram barely shows a change corresponding to lhe corruga­
tions '.arrows).
D: 5ifiling 2: 15-year-old younger brotEier had presented at
age 11 wi)h similar lundus appearance of fovea I scJiisis and
0 и Iff retinal corrugations.
E and F: Optical coherence tomography demonstrates Lhe
corrugations in lhe outer rulina in sibling 1.
G : The conruj'ii Lions disappeared by age 15 in sibl iпц 2.
Tii
1A —L a , H f i m ,ir !(l Ji. u i 2 tU J7 P A ir t e h i л п М ш и ш A D JU L :ir L fe ir t
A JI n ^ h la r L 'K t 'r v u i l
POST MACULAR TRANSLOCATION
SURGERY
l.imited translocaLion surgery for ntacular degeneration
and scars involves deliberate detachmetu of the retina by
injecting bubreLinal balanced salt soluLion and imbricat­
ing the sclera to foreshorten it, followed by flaLtening the
retina with air or g a i 3^ 7 t his maneuver shifts the macu­
lar neurosensory retina inferiorly, displacing it to overlie
a normal (fcPli bjse. Often this results in a retinal fold to
accommodate the redundant retina.1 , EietinaE folds
are seen occasionally in complete Lranslocations also.
Unlike folds involving the choroid and ItPE, folds of
the neurosensory re-Lina are not evident angjographically
(figures 4.06L and ] and 4.07h and F).
References A2. AlacilB C. 2aws И, GaJer M. el 3. - ejilt cir^Llir Црср анг asact alsj ^fli -aia Kla m с
laaa.^nebra iralicrialHi^ relada рцш 1. m eriaandsotriiti^tprem .Jhilanbc'
1. CaiigHri FE. Tres "f e [J.. № ЗД Jb. Cfca™. fcca ^jn J OptifHlmol l 97ft&6.o30-7. n;u-n:a' ЛЧйЙг1®;ВЁБЗ-71.
2. Beliaxni A Futdjs Хатсеа h Fuetepefaitie т^йату. Am .' ОртГ-alrEl 1955;4&73!-6. A'i. E£tiiif АЧ Gam uS .%&*} el l jstesluar« 1:1 юта a&xeltJw IT arlEf
3. FfiroatJ.D eLKvJJ R jH h a flB b g ^ a S B m rfa o p iH td ^ i^ b ffi.M o d Ptoti d ^ la a n a^l-iear-oid'jd.MeC Р й и Отся 1^20:7fl-6C
ОД-tiia fpo--971 J9:129-3&. 44. G d SiJM Stxafiitxc 21ai с! ш Ja r dcase^ сняпх s and йвйпеп. ^d ec. SL Li je.
A. GasJOfcitoHHGopkJ Has :r тгаоиа азеаж: а1.пхи£срс ard xaagraphc ЫМФ;. 1 3 а Щ й - г1
p'HH'talCT.Sl.LiiECi'fAiEth. 'ЭТО p. ЭЗ- 07 A1.i. LetuiHn С-A Herbel-Fiileui F. t o >Jret a:. MsrilesliflTB x Ja les жаккадтал! les
5. S is .04. Нкраму macu cpaiij. In: Go clreec Etems J. edttf. СоПмщшг> сДОИпвквд, lihT>jflise; cuelulats awerbil'scdares, Etil So: Offfrtalmolfr lSSl:8'.1G9-7U.
hxat^ Si' i-Lwi i DdK-ЕИег Eta na'e. hi I aic Д'ti fans; 13?2. j. ii3-EE. 4ti. Fjcmacx^ 'IG, JjiiaiGFL^'SLUijeCF: fcutir J-nJng; r artenXjeMlKCNsptea [Atujile's
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9. Kwl Al Utrtn EOD. Recream cf CTCiuial xiJs. Trim:. Air Асал OXfta ire Oltaiyrsa 43. Beter R3. Ё jfi.c .R Suider hi:uii kss n piejSHutoi ce'ra die b Hnlral r=on=! Ш\.
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h 1ша1 еззя. t o 0t T a riM ":йЗ:1П :3&r-9. 107337:39-97
10 tend ^ .О и агИ lads. Any-J 0|йНнЫ 1973:75:900-42. 53. Ha'rii A Sandera MO. Mxu ar -йи h-n frxr (aalDecs-ra. 5r J Oxite nr-a-
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This page mtentlonaSly left blank
Heredodystrophic Disorders Affecting the Pigment
Epithelium and Retina
Some of the heredodystrophle disorders appear to affect
pri 1Пч!лly the retfflal pigment epithelium (R P E J and only
secondarily Lhe relina (e.g., Bests disease], Others, such ль
ret Ini Us pigmentosa, appear lo a fifed both IAyers equally;
stitl others affect primarily the sensory retina (e.g., cone
dystrophies and lhe sphingolipidoses]. Some affect pri­
marily central vision, whereas others may afifed most of
Lbe visual field. Several heredodyslrophlc diseases Lhal may
prove to affect primarily the Rl’b and retina are frequently
associated with dmsen ant! disciform detachment [domi-
nanUy inherited exudative drusen; basal laminar drusen;
Korth Carol ina dystrophy and macular staphyloma).
BESTS DISEASE____________________
llesl's disease [viteliiform macular dystrophy] is an aulo-
somal-dominantly inherited disorder with variable pen­
etrance and expressivity.1 Linkage analysis has mapped
the gene for West's disease for pedigrees in Sweden and
Iowa to chromosome 11q i3 .j!!_',:" l'he gene responsible for
BVMD was cloned hy Pelrukhm and colleagues in 199S
and named Lhe (jH JSTJj gene. 4 it consists of
11 exons and 5S5 amino acids and spans IS kilobases of
genomic DNA. l'he gene is expressed predominantly In
the RPL ceils and the bestrophin protein is located mainly
on the basolaterai plasma membrane of the RPL and lo a
smalt extent within the (tPE cells, ihe protein is believed
to function as an Intracellular CaJj -dependent C]1 chan­
nel and an HCO^- chan n e t . Disruption of the ion
conductance across the RPL by abnormal bestrophin 1 is
Eikely responsible for the absence of light peak response
In the eiectro-oculogram (LO G ) in both patients and
unaffected carriers of llesfs disease.1-1 2A^6-i The disease
appears to affect primarily the RPh.
Previtelliforrn or Carrier Stage
Allhough vitelllform lesions have been observed as early
as lhe first week of life, the fundi of most palienls prob­
ably are normal during lhe first few months or years of life
(E'igures 5.0! A and 5.02A). Many carriers never manifest a
change in the fundus.
5,0 i Best's disease,
A—C : Changes occurring over a 21-year period in Ihis
27-ycar-old niitn with Best^ disease. l-fis fundi were con­
sidered as normal at age 4 ye a re (A). At age 7 yea re, be had
developed a lypicaE vi lol I i lot m lesion in EjoLh m acular ateas
(B). Visual acuin was 20/30 and 1-1 in bolh eyes. Al аце 17
his visual acuity was 20/10 right eye and 20/25 lefl eye (Q .
D-F: The brother of lhe patLenl illustrated in A -C was 10
yniars old when his fundi showed pardy scrambled viteE-
liform legions 11». His visual acuity in 1he rifjtr! eye was
20/15. At age 12 years, he relum ed com plaining of blurted
vision in hEs righL eye. NcHe the submacular hemcwrbage (Et.
Anjjiojjjam showed evidence of a (hom idal neovascular
membrane. A l age 30 years his visual acuity was 20/50 right
eye and 20/20 left eye. Note the white subretinal scar in F.
С and H: A l^J-ycar-old Еюу with Besl^ disease w ho
complained o f bluned vision Ln both eyes. His electre-
nculoyraphic findings w ere 1.00 in both eyes. Four months
later the vilellilerm lesions and surrounding relinal detach­
ment 'CJl had disappeared lH:-. Visual acuily was 20/20.
1 and J: This 13-year-uld female bad bilaterally symmet­
ric vilelliform macular lesions and a visual an.uily o f 20/1 5.
Angiograms showed m inim al fluorescence of bolh eye
lesions (probably pseudorlLiorescence cojrespo-ndiny to lhe
vik'lliform lesiom | .
К and L: A VilelEitorm lesion was presenL in bolh eyes oi Ibis
■^-year-old boy IК . and in lhe ri^ht eye i L i of his 73-year-old
grandfather wtio had a scar in the left macula.
[G end H « j u r t r s y ( J l I 3 r . M . i r k I . L l . ' i i l y ; k. B i d 1 c c j u r l c i - y iiC ]> r. i v i i c l i ^ч.г1
W Hints.)
Viteltiform Stage
3q infancy or in earEy childhood patients may develop
a sharply circumscribed subretinal. lesion that has been
Eibened to die yolk of a sunny-side-up fried egg [Figures
5.01 Б and Ir 5.02A, and 5.03CJ. Visual acuity at this stage
of the disease is usuaEly normal. Biomicroscopy and ste-
reop holography reveal a discrete lesion beneath the relina
[hal is Vi-1 disc diameters in size, yellowish, and usually
round or oval. Eiarly in the disease, little or no elevation
of lhe relina occurs. Subsequently the lesion appears ele­
vated as the yellow material increases in amount, and is
found in the outer photoreceptor zone, sub retinal space,
and within the ЕФЕ: layer. '- " I he color and pattern of the
EPE surrounding the lesion are usually normal. Variations
in size and stage of development of the lesion may be
present in the eyes of the same patient (Hgure 5.03A and
U). Ilie lesion initially may be evident only in one eye.
3n some patients the fellow eye may remain near normal
wilh 20/20 acuity throughout life.-M" ihe vitelliform lesion
may occasionally disappear spontaneously [t-'igure 5.OK!
and 11). I"he lesions may be eccentrically located and may
be multiple (h'igure 5 . 0 4 ) In a few patients they may be
unusually large and geographic in shape (i'igure 5.04G-1).
5ome patients may show a finely mottled pattern of yel-
Eowisb change in the KFL throughout the fundus (1-igure
5.03}:). liach of the affected family members illustrated
PravHe.iforr slage
Yibellrmlive s h l h
Atrophic stac?
bMl Eiest's Disease-correlation of clinical appearance
to schematic diagram
Л: Schematic diagram (jf pltibabie hiblopalhLiiagtc changes
in ЕЗкГь disease, Previlellilorm stage (see Fig. 5.01 Af. Stihlty-
Hide-up vilcllifom i slage 5.0 Ltil. RF’fc cells (arrows
iiic.1 distended iIh yellow pigmunt. V ilellinjplive £tage isoy
Fifjsi. 5.01 L5 and 5.03D). Disruption o( К Kb w ilh yello w pig-
inynt benEalh lhe? rutina ^nH atrophy o f rhe receplor ele­
ments. S « o u s di2tac:hmtjnl of lhe retina may t>ccur over lhe
vitelliform (see Fig*. 3.01 CJ and 5 .Q 4A and B )r the atrophic or
псоилзсЫпт sla^o (see ^iji. 5-Q3U. Л.1r<>ph cc Fitage. Choroidal
rtedVastuMijizaHan .inti cicatricial tfage inee hif^. 3.03H).
B and C: This 3b year old m ale with 2Q/S0 and 2(V200
vision respoclively bad a pseudo hypopyon appearing vitel-
liiorm lesion on lhe right and an alraphic lesion on the lefl.
D lo C : This young wom an w h s noted to have bilateral
maculopathy at 7. Photographs done at age 10 shows
mullifoc.il tile !Iiform depcreitH in ijoLh macula \D and E:.
Eleven years laEer, at aye 2 l ' r (here was an increase in the?
yellow material v.iLh a parli-a! scrambled евд ЗррвагагКпё ir>
bolli eyeii (F and O ). Her visual acuily -:lI ag^ 2-1 was best cor­
rected lo 2Q/40 righl eye and 20/2 5 left tiyu, EOCJ revealed
an. Arden ratio o f 1.2b on lh e rij'hl and 1.40 or> thy Jefl.
Q iu riusy. li ;ind (.!, Ur. l-bul S Lemberg li -C, Dr. tchiLird Cho-ntfy.
in figure S.O+A-h had several small, focal, yellow lesions
scattered in the fundus of each eye. These yellow punctate
Lesions may he the only manifestation of the disease in
some family members. '■
Vile'iforrr. Ыа;е
Sercus dstachmenl stage
Chorodaf neavascL.ar za li[n a rd
sisatnciEi ilage
Pseudo hypopyon Stage j.03 Best's disease.

Usually by lhe lime Lhe patient reaches puberty lhe yel­
lowish lesion shows evidence of disruption [Piggies 5.0] D
and 5.03A and L>). It appears lhal the yellow material is
partly taken up by the JJPh cells and the heavier material
gravitates inferiorly in lhe subretinal space. Some shifting
of this material may occur when die pa tie tit's head is tilled
Гог 60-90 minutes.11 ]Ъеге is thinning of Lhe RPE and
occasionally some clumping of pigment in the superior
portion of these lesions.
Scrambled-Egg Stage
With further disruption of the vitelliform lesion, multiple
irregular yellowish subretinal deposits produce a picture
likened to a scraEnbled egg. Multifocal yellow deposits may
occasionally be arranged in a more orderly ring distribution
near lbe periphery of these lesions (I igure 5.04C;). the visual
amity is often decreased lo lhe level of 20/30 to 20/40 in the
presence of extensive scrambling of the vitelliform lesion.
Atrophic Stage
Eventually all of the yellow pigment may disappear and
Eeave an oval area of atrophic KPt! (E'igure 5.03E-).
Cicatricial and Choroidal Neovascular
A -С: This 13-year-old black ^irl, one of Ibrce s ib lin g wi1 h
E 3 d i s e a s e , showed a partially scran-.Ejli’d vitelhform
lesion in Lhe Nfjht eye iand <l угтпчэЛ (.list iform нел г and serous
гласиЕдиГ dclachm eni in Lhe left eye (A and tf). Vinual acu ­
ity in Lhe right eye was 2Q/20 and in the left eye was 20/40.
Arteriovenous phase angiogram showed evid en ce of choroi­
dal neovascular membra ne I a now, Q-
D and E: This 14-year-old boy had Lhe vitellirupLive slrtfjt of
Best's disease. Note loss of yello w material in the superior
portion of the lesion and layering o f Lhis material inferiorly.
AngiognipEry fHji showed evidence of fluorescence superiorly
but not inferiorly in the region of the yelLowish material rnfe-
riorly. Later angiograms showed definite evidence of leakage
of dye in the superior half of lhis lesion.
F: The 37-year-oEd mother o f Lhe patient illustrated in D had
a visual acuity of 20/300. Mote Lhe elevated fibrous scar
benealh the retina and alropliv of surrounding relinal pig­
ment epithelium -К РЫ. There is a fine mol Lied palLern of" yel­
low discoloration oi the КИЕ throughout Lhe posterior pole.
A ngiugiaр1ту revealed staining of Lhe subretinal scar.
G - L : This fl-year-old ^irl was noted to have viteEliform
lesions in both maculas a l age -t. Ап 'Ч'Щ’ yolk"-! ike lesion
in ibt! righl macula (G1 is brilliantly auLofluorescent 'H i and
fills the subielinal spnee withoul overlying inner rutin ill dam­
age 1[). The [eft eye has a scrambled-ef^g appearance (Jl w ilh
a fibm lic star lhal is irrc^u I a rI у EryperautofuorescenL f К I. The
fibrous scar is associated w ilh subretinal fluid, impEying sub-
relinal neouascu Ia ri l a Li on Ll.
IG - L LtiurLiisy erf Dr. R a n t'd Kis/iihi .1. ■

Stage
Many patients develop evidence of one or more plaques of
white subretinal fibrous tissue, and in some cases there is sub relinal space (figure 5.03C). Il is probable lhat occult
evidence of choroidal neovascularization and hemorrhagic choroidal neovascularization is present within some of the
detachment of the macula (E-'igures 5.01 E and 5.03E5, C, subretinal plagues of fibrous tissue.
and !■These latter patients eventually develop a while Peripheral visual fields, electroreLinographic finding,
or partly pigmenled disciform scar (E'igures 5.0]F and and dark adaptation in these palients are normal. Color
5.03P). The central vision is generally 20/100 or Less al vision in the late stages of the disease may be mildly dis­
this stage of lhe disease. Serous detachment of the retina turbed. Ihe fiOti is markedly abnormal wilh the light lo
may occur at any stage of the development of vileUiform dark ratio usually being below 1.55.'vM jU EiOGs of carri­
lesions (ligures 5.01 Щ 5.03Л, K. and D. and 5.04A and Н]. ers of lhe disease usually yield a subnormal result. E]alients
In the vitelliform stage the early phases of angiography who are bolh homozygous and heterozygous for lhe fiestl
demonstrate complete obstruction of lhe choroidal fluo­ gene show low Arden ratio, thus making lhis feature mosl
rescence by the lesion (Figure 5.0] J J . -- Lli I here is no gen­ characteristic of lhe condition. Vitreous fluoropholometry
eralized obscuration of lhe choroidal fluorescence such shows no evidence of'breakdown in the outer blood-reti­
as occurs in Stargardfs disease. During the later stages of nal barrier wilh few exceptions in patients with advanced
angiography, (he vilellifoim lesion may appear nonfluo- macular degeneration.' : 'L'he disease is inherited as an
rescent or may appear to fluoresce slightly. Possible expla­ autosomal-dominanl trail, best's disease usually occurs in
nations for ihis apparent fluorescence include reflected Caucasian palients but may occur occasionally in Africans
vitreous fluorescence from the surface of the lesion, and Asians (Pigure 5.03A-C).11
improperly matched exciting and barrier fillers, and auto­ Visual prognosis is good for al least lhe first six decades
fluorescence of the yellow lesion. As the yellow pigmenl of life.n Most patients retain reading vision in at least one
gravitates inferiorly,. angiography in the area vacated by the eye throughout life. The progression of visual loss is slow
yellow material reveals evidence of early fluorescence sec­ and occurs for the mosl part beyond lhe age of 40 years,36
ondary lo de pig me mat ion and late staining of the altered Acute and permanent loss of central vision may occur in
RPfc (E'igure 5.03L). Often ihere is a narrow zone of hypo - association with bleeding from subretinal new vessels
fluorescence surrounding the atrophic lesion. Angiography (Figure 5.01 E). A macular hole may occasionally occur in
permits detection of choroidal neovascularization and patients with Jiesl's disease as well as in palienls wilh aduli­
shows evidence of staining of fibrous tissue present in lhe on set foveomacular dyslrophv or pattern dystrophy.'' ■
 The hlstopathology of the vifilifo rm or pseudo­
hypopyon stage оГ Lhe disease is unknown.' 1
Eiistopathologlc report concerned a relatively early scram­
b l'd -egg phase of the disease.1 One report concerned one
eye with mild pigment macular changes in a 6У-year-old
man with advanced degeneration in the fellow eye."
bindings in these reports were соnsistent in theiF dem­
onstration of a generalized RPE abnormality that was
associated with an abnormal accumulation of lipofuscin
granules in the RL:h and within macrophages in the sub-
retinal space. None of these studies, however, showed the
extensive lipofuscln storage characteristic of Stargardt's dis­
ease, a finding in keeping with the absence of a dark cho­
roid angiographically outside the area of the vltelliform
Lesion In patients with Best's disease.
Other histopathologic findings in best's disease
included a periodic actd-Schiff (t’ASj-positive, acid muco­
polysaccharide-negative,. electron-dense, finely granular
material in the Inner segments of the degene rat Ing pho­
toreceptors and Muller cells recently Identified predomi­
nancy an abnim iiil li 'iili.-i [илt-.Ti.il hc:u\Uh die
KJ^li cells In the region of photoreceptor cell loss, and nor­
mal chorlocapillaris.1' Breaks In Bruch's membrane and
choroidal neovascularization have been demonstrated.' _l
One group of authors concluded that the sensory retina!
changes were probably primary and the ItPE changes sec­
ondary. ■' Ihese studies, together with the In vivo dem­
onstration of autofluorescence of vitelllform lesions In
liest's disease by Milfei;7,32,36 1' suggest that the yellow pig­
ment may at least In part be caused by lipofuscln. There
is no fluorescein angiographic evidence in this disease-
however, for a diffuse market) lipofuscin storage disease
such as occurs in Stargardf's disease [see pp. 278-284).
Histopathologic examination of a S 6-year-oEd homozy­
gous for E tS T i gene showed accumulation of lipofus­
cin.. a large component of it made up of A IL, within the
ЁР 0 cells. OLher RVli granules were melanoJiposomes.
lixtraction. of the granules in this eye and another S I-year-
old's eye heterozygous for the gene showed the lipofuscin
to be mostly made up of A 2 L similar to that found in dis­
eases caused by the ABCR transport gene abnormality."1'1
]^he vtteEliform stage of Liest's disease should be differ­
entiated from other diseases that cause solitary yellowish
macular lesions; for example, dominantly inherited, adull-
onset vite t i t form foveomacular dystrophy (pattern dystro­
phy) (see Hgure 5.06-5.08), basal laminar drusen [figure
3.29), acute exudative vimlElform maculopathy (figures
11.30 and 11.31). and fundus flavimaculatus [Slargardt's
disease) with large central flecks. I he early age of develop­
ment of the yellow lesion and the progressive vtteLltrupti-
form changes are essential findings to differentiate patients
with Rest's disease from those with aduft-onset vitelliform
foveomacular dystrophy (pattern dystrophy}, because the
Eatter disease may be associated uith subnormal HOtls in
one-third of cases and because both are dominantly inher­
ited. hour oLher yellow lesions that may simulate West's
disease include focal serous RPE detachments containing
3.U4 Multiple vilelliform lesions in Best's disease.
One
A—E: This 25-year-old physician com plained of mild visual
blurring. Visual acu ily in lhe eve was 2CV20 and In
the left eye was 20/15. Note Ibe mu ILi pie slijjhlly elevated
lesions игаttflfed throughout the posterior pole of both eyes
i A and E3■. Clinically, Ibese k'sions resemble Somewhart a
somus detachment of [he retinal pigment epithelium IfiH’E;-.
Note the ill-defined braiders of ibe yellowish biaterial in
Lhe large central I E»i езл s. LaLe angiogram (C) in Ibe lefl eye
revealed no evidence of staining o f the large central lesion.
The slighl fluorescence of lhe paracemrnl lesion^ was prob­
ably caused l>v pseudoftuoTescrnce. The patient's elcctro-
oculographic findings were definitely abnormal (1.1 ri
eye and 1.3 left eye). SeveTaJ months; afler lhese pholo-
graphs, he became asymptomalic and remained so for
approximately 1 year, Wfiert lhe symptoms reLurned for
approximaLely t>months. H e again became relatively asymp­
tomatic. ] 'holograph of lhe !efl fundus taken 21 months arier
A anti li shows that the Central lotion hat largely rfesolVed
ID). The other lesions appear smaller, more discrete, and yel­
low in appearance. Sim ilar findings w ere present in Ihe right
eye. His visual acuity at Ihis time was 20/30 in Lhte right eye
and 20П 5 in the Lefl eye. Angiography IE] showed evidence
of s(jm« Ih inning of the HHb inferior to Lhe fovea I area. The
paracenLral leilflrts apfmared nonfluorescenl.
F: The left lu rd u s of the 15-year-old sister of Ihe patient
illustrated in A-E. Note the multiple, small, discrete, yello w ­
ish lesions scattered :n the posterior pole (arrows]. Another
brother and the father had sim ilar punctale yellow spols
in I be fundi. All 1hree had a markedly subnormal electro­
oculogram. The fundi and electno-oculographic findings of
another sibling and the moLher were! noimal.
G - l: Large m ullifocal vitellrform lesions in a 46-year-old
wom an who gave a 2 -уеДг history of bkur-ed vision. Her
molber bad tailing vision In late aduilhood, and a malernal
cousin had m acular degeneration. Note the pari I у dm ru pi L:d
lesion in the righl macul.i (£j) and the largu nondisrupted
lesions in lhe left macula '.Hi. Twenty monlhs later Ihe cen ­
tral m acular lesion had enlarged ill. Visual acuity was 3/200
in Ihe righL eye and 2 0 /4 0 + 3 in lh e left eye. Her electro-
□culugraphic findings w ere definitely abnormal. Her electro­
ns! inographic mdings w en: normal. Angiography revealed
tlie inlact vitelliform lesions to he nonfluonescent.
deheinoglobinized blood pigment, some cases of central
serous retinopathy with subrelinal fibrin, resolving sub-
retinal hematomas, and unusually lar^e acute solar macu­
lopathy lesions.10. To be confident that one is dealing with
Hesfs vitelliform dystrophy rather than some other type
of dystrophy, the following art required: ( 1 ) the presence
of one of the recognised polymorphous lesions typical of
Best's disease; [ 2J dominant mode of inheritance; (3) mod­
erate to severely subnormal КОС findings; and (4) onset
and natural course of the disease typical for best's disease.-'-
Without tills documentation the diagnosis of Best's disease
is open lo question.-,:ii|l:-'■ Gene testing for the filiSTl
gene with the presence of the above features confirms the
diagnosis, future identification of specific gene defects and
the nature of Lhe vitelliform material will help elucidate
the pathogenic relationship of the various disorders that
demonstrate similar yellow lesions in the macula.-^-11'
 Multifocal viletliform lesions may occur in patients
wilh llest's tjfeease (1'tgure 5.04).12 Most palienis with
multifocal vilelliform lesions, however, have no other f vi­
deлее of liest15 disease (see next secLion). lhe lesions may
vary in size. Some may he several disc diameters or larger
in si^e and often have some irreguEarily tic their contour
{E'igure 5.04G-l). These larger lesions frequently dem­
onstrate partial resolution or disruption. Multiple round
flecks of yellow pigment may be arranged in a circular or
oval distribution near the periphery of the partly disrupted
Eesiom [figure 5.04C}.
BesM gene has also been implicated in aulosomal-dom-
tnanl vitreoreti nochoroidopathy [ADVlRC), autosomal-
dominant microcornea rod-cone degeneration syndrome
(ADMRCJS], and autosomal-recessive beslrophinopalhy
(ARI1], all with extra retinal features implicating the gene
Lhat m i)1 be involved in ocular development.1’’
A U T O S O M A L D O M IN A N T
V IT R E O R E T I N O C H O R Q ID O P A T H Y
ADVlRC is a hereditary pigmentary dystrophy described
in 1932 by Kaufman and ]t has an autoso­
mal-dominant inheritance pattern and is characterized by
peripheral pigmentary retinopathy for 360° wilh a discrete
posterior boundary near the equator (figure 5.05 C-H)
associated with punctate whitish opacities in the superfi­
cial retina along with vitreous cells and fibrillary conden­
sation. Frequently, peripheral retinal arteriolar narrowing
and occlusion, evidence of retinal neovascula rizalion..
choroidal alrophyr and presenile cataracts are present
Evidence of blood-retinal barrier breakdown is seen by
cystoid macular edema. *
These patients usually do not have symptoms of night
blindness. The electroretinogram [E:RC) is normal or only
slightly reduced. 'Lhe HOG is variably affected, with Arden
ratio ranging from normal lo subnormal. There have been
a few cases with late cone dystrophy.;1 The gene defect has
been localized lo the ВЕ£ П gene with missense mutations
Ь.i>"p Autoso т а 1-dom ina nt vi tree re tin ocho rotdo pathy.
A - H : А 47-уг>лг-[)](Н Hannan af Hu^ucNiot iinteslfy pre-
sftited Wiilh pFDgffissiv^ visual E>lLirr i 1тц Find {jlars? hdf л уалг.
There was л с fanHly hislDry of tisual pruhlunn? ап-d she WaK
uthtirwiae hci-nill hv. Visual acuity w as 2(V25 in 1Itu- Tiftht eve
atld 20/40 in the left eye. .Vlild bilateral poifcrtor subcaMUr
Iл г cataracts vvuie present in bolh gyek. The publerior fifties
wcf(? normal in M th eyes A And 13 . M id peripheral т п г к ь
had ret ins I pi^menl tipil hej I i Ltm iR PLi mrgratiun in I hr:1form
ut Езопе spicules that Were li^liLly lo an ed <дпН sym m elricaI
between lhe two eyes (C-E). Ркю гезсем angifjgr-ifrt was Ш
mn\ in Lhe pteleriftr pule: Lhe periphery showed diffuse irruis-
inishicjn hvperfluoresicen се : n lurspc ised w ilh bEoclcijje from
pigment spletiles.
and exon skipping on the long arm of chromosome
^ 3 2 ,5 2 ,5 3
A U T O S O M A L - D O M IN A N T
M IC R O C O R N E A R O D - C O N E
D Y S T R O P H Y , C A TA RA C T W IT H
S T A P H Y L O M A ________________________
A subgroup of paLienls who have all or some features of
ADVlRC may also have microcornea and shallow ante­
rior chamber wilh evidence of subacute or acute angle
closure glaucoma. Some of these patients show posterior
staphyloma and some of them are myopic.7*'1 The inheri-
lance pattern is autosomal-dominanl,. and the gene again
has been ascribed lo the F fS T l mu la tion 'l"he HOG is
abnormal in all patients wilh AE3MRCS syndrome. A full-
field EiRG may show subnormal pholopic and scolopic
responses. W ilh time, ihese patients show progressive ГЖ т
changes wilh severe rod and cone photoreceptor dysfunc­
tion, unlike patients with ADVlRC who are relatively sta­
ble. lhe ADMRCS syndrome is generally more severe than
ADVlRC. However, there are family members who have
overlapping findings of the two conditions.-
A U T O S O M A L - R E C E S S IV E
B E S T R O P H JN O P A T H Y
Jhis condition Was described b y Burgess et al. in 200Й. "
It usually starts wilh cenLral Visual loss al да age of onset
ranging from 4 to 40 years., and the mean age Ш onset is
approximately 25 years. The visual acuity often deterio­
rates lo [ess than 20160 m both eyes within a few years.
Parents are generally hyperopic and show shallow ante­
rior chambers and may present with sub acute or acute
angle closure glaucoma, fundus examination shows
irregular RPt alterations with whitish subretinal depos­
its that are seen throughout the relina, preferentially in
the macula and Entdperiphery [I'igure 5.05J-1.J. Jlelinal
edema wilh neurosensory retinal detachment and sub-
relinal fluid may be observed in the macula occasionally;
this can he confirmed by op Lical coherence lomographv
(О С Г). E’alienls may not show the vitelliform lesions that
are characteristic of best's disease. Ihe macular lesions
may evolve inlo atrophic scars causing a further decline
in vision." lhe LOG is severely reduced or absent to
Eight rise. rl1te focal pattern EiRC in the macula is mark­
edly abnormal, indicating severe macular dysfunction. The
full-field E:RC shows reduced and delayed rod and cone
responses indicating pan relina I photoreceptor dysfunc­
tion. On angiography, there is widespread patchy hyper­
fluorescence due to R P t atrophy and retinal edema. iliese
areas correspond to areas of increased fundus aulofluores-
cence (Kigure 5.05].), suggesting lipofuscin accumulation
tn the pigment epithelium. The areas of ftPE loss show
decreased fundus aulofluorescence. Eligh-resolution OCT
of the macula shows photoreceplor delachmenl from the
pigmenl epithelium, disruption of the photoreceplor layer
but persevered inner relinal layers [ Figure 5.05M).n 55
Those palienls who are heterozygous to lhe mutation are
entirely normal clinically and eiectrophysiologically.
All the three conditions described above are caused by
mutations in the tiESTi gene, the same gene that causes
Best's vile Hi form macular dystrophy Whereas Best's,
AUVIRC, and ABM RCS syndromes are autosomal-domi-
nanl. АЦВ occurs in the presence of homozygous or com­
pound helereozygous ЙЁ5П mulalion.
j.O."- Continued
Au losum aE-recess ive beslro phin opathy,
l- M : Hundus photb^fajph of fi 30-year-old Female, who car­
ried two flfomoZyBtSLis nunvense muLalions in the B E S T 1
(^one. The visual acuily was 20/32 i0,63) in thy right eye. A
faint round yellowish lesion was present in lh e cenLral niflt-
ula. TJii^ lesion was su«m inded liy sume yellow-while ill-
defined spots. In addilion, [л i nl lv .Hrophi< hy pop igrriiented
ei neat could Ew noted around Lhe retinal vascular arcades
(11. Fluoreicein angiography revealed diffuse patchy hyper-
liuorascence Ihroughoul lh e fundus., com palible w ilh mild
diffuse atrophy o f ihv K f t . Around the fovea similar hyper-
fluorescent changE» w ere present, Joj^eLher with slain ing of a
small subretinal scar inferior of the fovea Ij and Ю-
fundus aulcfiuorescence p a g in g showed i^ight aulo-
fiuorescenE^ changes cen! rally in lhe macula. The brighl]y
aulofluorescent dots corresponded lo fbul outnumbered' the
yellow-while spols seen on ophthalmoscopy. These lesions
therefore seemed to reflect increased amounts o f relinal
lipofuscin. Around and beyond Ihe relinal vascular arcades,
small iire^ular spoLLed areas of increased and decreased
HuLofluorcscynce w ere noted i.L).
Speclral-domain optical coherence Lomography image,
scanned horizontally Ihrough (he macula, revealed hyper-
re flee Live materiaJ - SpsSfbly shed pholoreceptoi ouler seg­
ments between the slighlty elevated retina and the ТСРЁ (VII.
IA -H .LTji.irlLi'.y nl ■!Jr. K .in jiL i >I',.i ii'>v.11; U .M c u u г|г:ьу 11 Г U r . < a m ijc B w n .i
Nearly all mutations identified in Be&t's vitelliform
macular dystrophy and adull-onsel foveal macular vilelEi-
fonu dystrophy, a Lype of pattern dystrophy, are missense
mutations. Those mutations causing AIA'ERC and the
MRC5 syndrome are splice mutations. '" ' leading lo
in-frame deletions or duplications, lhe null phenotype of
ARB is caused by homozygous or compound heterozygous
nonsense or missense WES'H mutation.'■ ''': The variable
expressivity and penetrance probably account for lhe wide
variation in the phenotype of these conditions. It is likely
they are also dependent on olher genetic or environmental
modifiers lo manifest all features of the condition.
M U L T IF O C A L V IT E L L IF O R M
L E S IO N S IN PATIEN TS W IT H O U T
E V ID E N C E O F B E S T S D IS E A S E
MuUifocal vitelliform lesions with the same features as
those occurring in Best's disease, in l>r. Class' experience.,
occur most frequently in patients ivith normal EOG find­
ings and a normal family history (figures 5.L16 Hind 5.07).
1'Luorescein angiography typically demonstrates non fluo­
rescence о/ lhe yellow lesions (Figures 5.06C and L and
5.07Н]. Occasionally, however, the yellow Lesions demon­
strate early hypeFfluorescence {Figure 5.07]}. As in lhe case
of [Jest's disease, the yellow lesions may disappear (Ngure
5.07A-D}, lhe frequency of normal EDCi finding* and a
negative family history in patients with multifocal vitel-
Liform legions suggest that most of these patients do not
have either Best's disease or pattern dystrophy, ihe absence
of a family history alone does not entirely exclude these
diagnoses, since many affected persons with liest's disease
and pattern dystrophy are asymp to malic. I his condition
should he differentiated from acute exudative multifocal
vitelliform maculopathy, an acute-onset inflammatory dis­
order of so far unknown cause..'" ' ' 1A RIi,v '5 and paraneo­
plastic vitelliform maculopathy1" E J e u t m a n ' reported
a patient with loss, of central vision for many years asso­
ciated with peripheral and macular vitelliform lesions
together with elecLroretinographic changes compat­
ible with a rod-cone dystrophy, it is possible t>eut man's
patient had autosomal recessive bestrophinopathy.
S.0*i Multifocal vitelliform lesions in adull patients
with a normal family history,
Л-C: Th is 39-year-pld healthy black mail with a
history of melHTTHjrphopsia had a visual acuily of 0 in
Lhe r i eye and 2(1/25 in the lell eye. The partly disrupted
param acular lesion in the light eye 'A ) w<ia partly hvpoflu-
crescent (Cl. The yellow lesions w ere nontluorescent. His
eleclio-nculDgraphit: finciin_qs wore1 normal in the ri^hl
eye and 1.Й7 in Ibu left eyel.
D -F: ТЫн 34-уеаг-оId miin complained of hazy vision in
the left eye ol 5 months' duration. Visual acuity in hoLh eyes
was 2(1/20. He had m-ulliple vitelhform lesions iit bolh eyes.
A larj^e vi te 11i form legion involved the left macula (compos­
ite рЬо'оделрЬ, D). A ]luid level was evidEЛI bioniicfoscopi-
c H ly in a lesion nasal Id lEic left b p tK disc (aJrtAV, !>■ and
an^io^japhically in the largE m acular lesion -5-1егепап^ю-
^rams, E and F-l. M is family history was rwgativ£, JHis eletlro-
ocuio^rani Arden ratio was 1.0 Ejilalerallv'.
G —L: This 54-year-old man noted blurred vision in the ri e ft
eye. JHis famiJv hisLor\ was negative. Visual acuih' was 2C1/-E0
i:i I !if.' г,L;111. eye rind 20-'40 in lhe- loii о.ч1. Гhere.1 wcvo m ul­
tiple vitelliform lesions in both eyes (G and H ). His electro-
cicuioyrapbic findings w ere subnormal П .5 in (he ri^hl
eye and 1.4 in lhe left eye}. H is electroretinographic find­
ings wi'Jt? normal. His color vision was severely form al.
Sevt'n yearF- laler the lesions in lhe ri^ht eye w ere pari I у dis­
rupted ill and he had acquire^ a c e n ta l v ite llifomi [esicm in
the leEl macula (Jl. Visual acuity was 2 0 /2 0 in the right eye
and 20/40 in the lefl eye; Angiography revealc*d lltal Ihe dis­
rupted lesions in holh eyes w ere hyp^rfl^J о r e s e l l flv and L-.
The nondisrupted lesions in Ihe reft eye w ere nonfluorescenl
Ш . The multiple lar^e "sunny-siide-up'' lesions present in lhe
sixth decade o f life and the absence ol a history of affected
family membeTsarea1ypic.il for Bests disease.
[C i—L LC JU rl^ Sy cM L Jr. StL^ nhur, I. J-LV'-in. I n
 СП
.M iii'h fo L H .1 Viteltijm m Б й я о т т г гиг i'u tim fc iV ithtnti fcviderttSt o f B e s ts J-JiHLTnsf

(p j
A U T O S O M A L - D O M IN A N T
PATTERN D Y S T R O P H IE S O F
T H E RPE
Autosomal-dominant pattern dystrophies fire character­
ized by lhe development, usually in midlife, of mild dis­
turbances of central vision associated with a variety of
patterns of deposits of yellow, orange, or gray pigment in
the macular area.4"1' 52-11^ Jbe prognosis for retention
of good central vision in at least one eye until Kite adult­
hood is good. "Ehe EOQ may be slightly or moderately
subnormal. 'J'he ERG is Lypically normal. These dystro­
phies are usually inherited as an autosomal-dominant
trail. Mutations of the peripherin/H£JS and slow gene (Pro
210 ARti) and codon 1 67 of the gene were first dem­
onstrated in family members of patients with dominantly
inherited pattern dystrophy.1''1 i0S Since then several other
mutations of the peripberin/fJDS gene have been found
in families and sporadic cases of pattern dystrophy.'"1, b0''
O f importance are the various phenotypes, often within
families seen with the same genetic mutation.■ u' ,Dfi^]Lfl
In addition to the association with different phenotypes
of pattern dystrophy, peripherin/HDS gene mutations
are associated with central areolar choroidal dystrophy,
autosomal-dominant retinitis pigmentosa, autoso mal-
dominanl cone and cone-rod dystrophy, retinitis punc­
tate albescens, and digenic retinitis pigmentosa.1''' 1 L 1
One family demonstrated phenotypic variation, includ­
ing retinitis pigmentosa and fundus flavimaculatus. Iiyj The
peripherin/HDS gene localizes to chromosome 6p i l \1f
spans 26 Idlobases of genomic DMA, and contains three
exons. Ihe gene product :o f peripherin/WJJS is an integral
membrane protein peripherin/WRS within rods and cones,
and plays an important mle in the photoreceptor outer-
segmenl morphogenesis by managing disc formation.,
alignment, and shedding.
leased on the pattern of pigment distribution, pat­
tern dystrophies have been subdivided into al leasL five
principal groups. A few patients will show different pat­
terns in the two eyes.. A patient may show progression
from one pattern to another over a period of years. Some
pedigrees will show any combination or all fonr of the
patterns of fundus change described in the succeeding sec­
tions.'0 1 ' M" Jror these reasons it is probable that these are
closely related, if not expressions of the same disorder.
j.07 Multifocal vitelliform lesions in adult patients
with normal family history and normal or subnormal
electro-oculographk findings,
A^E: This 4D-)№r-aid mart presented t(] his- local physician
in 197.1 Ijecause of diffkully wilh. dark adaplation. H is visual
acuity Was 20/20 in bolh eyes. Yellow lesions were noled in
bolh fundi. Hi-s electrD-ocuiogrnphic findings were normal.
Two years later his acuity was reduced to 20/25 right eye
and 2iViJ0 left Eye. 1hurt1 Were m ultiple geographic yellow-
orange lesions in the parncenlral region o f bolh eyes and a
scar En the left m acula IA and E3>. Two years later (he fundi
wore unchanged (QJ. By 1У8-Е, а II o f Lhe yel Jow-oran^e
deposits had disappeared, leaving in their stead geographic
aLrophy of Lhe rulinal pigment epjlhelium (D and b). His
■. isu-.il acuity was 20/25 righl anc* 2Q/20Q tefl eye. His
findings were unchanged in January 1ЭЭ5.
F-H: " ■ii - - I-'-c.ii-. Id w< man pri'senlud Iл:■
■..л -с of ,i Г -year
hislory of visual loss. Her visual acuity was 20/40 bilaterally.
1here w ere multifocal yellow lesions in Lhe macula and .u?i-
tapnpiliarv area bilalerally d: and Ci). Angiugraphicallv Lhese
were ncmfluorescent centrally anti were sujm unded by a
ling of hyper fluorescence (Hi. b.loUroreli nogram, eleclro-
qculogram, d-нтк adapLalion, and color vision w ere normal.
Sixleei: months I ale г her findings wune unchanged.
1-L: lhis healthy 20-year-okl man noted а сел Ira] scotoma in
both eyes. M ultiple yellow lesions w ere scattered in the глас­
ила and jLmtapapillajcy rugion of bolh eyes Mi. These lesions
showed eadv iivperf luorescercce anti lalo staining (JL Two
mortLhs laLer he had developed evidence oi s'jbretinal fluid
artJLmd each of the y e llo w lesions :K . His electro-oculogram
was low потгшн! in boLh eyes. Eiighleen months later the
fesions had disappeared ^LJ and his visual acuity was 20/15
in Ijolh eyes.
F-H аэигЬну (if Ur. R id U fd j. r. i(jl(ibL r^. !-L tu u h lay ■
..i LJr. МЫнт! N
Jtthnsun .ind i^ilriLk I. ( -щкл'у..
Croup 1: Aduft-Onset Foveo macular
Vitelliform Dystrophy
Palients wilh adull-onsel foveo macular vilt:LiLft>nn dys­
trophy share lhe following clinical features: ( I ) vianally
asymptomatic or mild visual blurring and met amorph оp-
sia in one or both eyes, usually wilh lhe onset between
ages 30 and 50 years; [2) symmetric, solitary, usually
L/3-J disc diameter-size. round or oval, slightly elevaled,
yellow sub relinal lesions, often wilh a central pigmenled
spot in each eye (Figures 5.0S-5.J0); and (3) small yellow
flecks that may or may tiol be present in the paracenlral
regioii.62' l"L,6li'bti,:’|,,_:7i-?d h':31 ]he symptoms of
blurring and melamorphopsia are often unilateral despite
Lhe frequent presence of bilaterally symmetric lesions.'['he
symptoms may improve spontaneously hi ilia Ily, lhe yel-
Eow lesion may be present in only one eye. Although most
of lhe foveal lesions are approximately 1/3 disc diameter
in size, occasionally Lhey may be larger and misdiagnosed
as lhe ‘'sunny-side-up" stage of Best's vilelliform macular
dystrophy or as bilateral serous detachment of the RPh
(Figure 5.09J. Jhe yellow foveal lesions often develop a
central gray or orange clump of pigment lhal biomicro-
scopically may show evidence of the pigmenl extend­
ing into the posterior relinal layers [Figures 5. USA and B,
5.09D, and 5 .10A and B). Later the foveaE Lesions may fade
and leave an irregular oval or round area of depigmenla-
Lion of Lhe RPL (figure 5.0SEJ. Some palienls eventually
develop additional paracenlraE yellow deposits, often in
a triradiate pattern (I’igure 5.0SU-FJ. Fluorescein angiog­
raphy during the early stages of the disease shows either
a nonfluorescent lesion (I'igure 5.09C) or, more typically,
a smaEL irregular ring of hyperfluorescence surrounding a
central non fluorescent spot [halo) (J:igures 5.0ЙС and I
and Some of lhe exlrafoveal small yellow lesions
show discrete staining, such as drusen (Figure 5. IOC), and
others, siEnilar lo the foveal lesions, are either nonfluoies-
cent or have a halo of fluorescence surrounding Ehem. '['he
yellow and gray components of the lesions are brightly
aulofluorescent and lhe depigmenled KPF in late lesions
are hypoaulofluorescenl (I'igure 5.JJ К and L),
S.OS Adull-onset ioveomaсular vitelliform pattern
dystrophy.
A —C : Thin ЗО-уеаг-old yvtiite woman- developed melrtmor-
phopsiS find a positive ncotoma in the righl eye b weeks
before exam million. "lhe symploms had im pn ^ et) by the
lime of fea^minatidh. Visual acuiLy in lhe? rij^hL eye was
20/25-1 and |-1 and in the left eye was 20/50 and J-l.
Symmetric^ slighlly debatBd, ovai, discrete, one-LhiTd disf
diameter size, yello w lesions w ith a central pigrnenL clum p
weTe presenl in lhe Гоуео! в г areas ;Л and JJi. There w e ix sev­
eral sm.dl yelJtnv deposils En I be paracenlral area of I be lefl
eve :arrows}. Her eledno-CHJulographic findings went; sub-
потгпа! ■1.4 in both eyes}. Angiography showed а Flupresc r:nl
ring centered En lhe fovea of each eye I t ] . Yellow lesions in
lhe midperiphery iluonistjed iarrows).
I!): Jiight Dye erf Lhe 54-year-old mol her o f Ihe patlpnl i3lu*-
Lraled in A - t . She noled mild distortion of vision in her Lef1
eve 10 ye,]re previously. Visual acu ily in Lhe righl eye was
20/40 and |-2 and in Ihe lefl eye was 20/30 and J-2. In Lhe
center Ы Lhe fuVea is dn iTregular, found ^rea of depigmon-
Lalion surrounded by m ulliple yelJowinh deposits. A lew
deposits I arrow i are presen I in lhe exlramaculnr area. Her
elecLro-ocu-lographic findings were subnormal '1.22 in the
righL eye and 1.40 in Lhe left eyef. The angiographic pattern
was similar to LhaL in tl.
t Hind F: Tlie 70-yea r-o Id maternal grand molher of Lhe
paftmt illuslraled :n A-С had noted mild difficulty with read­
ing in her left eye fo? the lireL time SO years previously Ihis
remained unchanged since that lime. She was asymplomaLic
rn her right eye. Her visual acuily En bolh eyes was 20/40.
Note Ihe central area of d epi gm ел Ial ion of lhe reLinal pig-
nnent epilhelium (arrow, tj and fainlly visible jjeripheral
flecks. Angiography showed a reticular fjatlern of irregular
hyfierl'luorescence (FJ. H e r electro-otukir^raphic findings
were subnormal (1.0 in both eyesf.
G - L : Central yellow Lesions resembling inanimate and ani­
mate objecls, e.g., spaceship I d . thicken (H and I:, utinfish
(|)f airplane iK]f and hobbyhorse -I ). NoLe lhe yellow para-
cenlral flecks.
 This (c m of pattern dystrophy was observed in females
in three successive generations in one family (J-igure
5.0BA-F] al the fiasco m [’aimer Lye Institute. I his family
was originally reported in 1974 by this author (GassJ as
having a peculiar foveomacular dystrophy, later referred
[o as adult-onset vitelliform foveomacular dystrophy.81-^
Recently a mutation of the periphertn R D S gene has been
demonstrated in two of these patients.1'"' lhe mothers of
two unrelated patients with adult-onset fo ve o macular
vitelliform lesions showed evidence of butterfly dystrophy
(E'igure 5A2A-G}.
Large vitellFl'orm lesions associated with adult-
onsel vitellifofm foveomacular pallerr dystrophy.
A -F: This 51-year-old woman's visual acuily was 24VSO bilat­
erally, ih e had discrete slightly elevated, yellowish Eesicms ir>
Lhe cenler o f both та»: ulae A ап-d К Angiography rnvmalcd
Iho lesiun-H to be nmflgorescenL -:0. Same patient ..J years
Ia Lei ID and E). Note the pigment in Lhe tenter ol the lotion.
Visual acuity was 2pyl60. The an^io^ram now sffcAved an
irregular ramerfludtitoCfiHt rin^ centered in Lhe fovea It1:.
Sim ilar chan^us- look plate in Lhe left m acula during Ltiis
same period of lime. The palienl qave no family hislory of
m acular degeneration. H e r eleclro-oculo^raptiic Yinclin ^
were потпла].
G —L: This й З -year-otd w om an 's visual acuity was 2 D/50
bi laterally. Note the large vrtellilurm Eesicms (C and H). Her
eleclro-oculogniphic findings w ere normal i2.a in the riцЬI
eye and 3.5 in the LefL eye I. The lesion in Ihe Eelt eye was
пол fluorescent initially (If. La Lei phases fL and Kr slereo,
and L ■
. however, suggested pos-bible underlying cEiurttidal
neovasculari nation.
lA-4- frrun (-i.ii-ь.®11
 Unlike those in Kesl's vilelliform macular dystrophy,
the vi tel li form lesions in patients with pattern dystrophy
usually first appear in lhe fourth decade or beyondr are
generally smaller, and do nol show disruption and layer­
ing of Lhe yellow pigment in the depcndenL portion of the
Lesions. In some families there is an overlap in the features
of best's disease and patLern dyslrepjhy.31
Croup 2: Butterfly-Shaped Pigment
Dystrophy
When lhe gray or yellow pigment is arranged in a well-
organized tri radiate pattern con fined to (he center of the
macula in a symmetric fashion, it has been likened to the
shape of a butterfly {l-'igure 5.12A -C).r-: A zone of
depigmentation occurs around the pigment figure, '['he
optic disc and vessels are normal. Some palients have a
reticular pigmentary pattern of drusen in the periphery,
lhe early phases of angiography show hyperfluorescence
that outlines lhe non fluorescent pigment figures in the
macula (Figure .i. 12C). the shapes of the central yellow
Eesions in pattern dystrophies vary considerably and may
simulate a variety of inanimate or animate objects (l-'igure
5.03C-L).
э.1£1 Ginicopathologk findings fn adult-onsel
vileEtifо rm loveomacular paltern dystrophy,
A-F: This 06-yea r-old wom an had a 4-monlh hisLorf ol
gradual decrease of vision in bolh eyes. Her visual acu ­
ity was 2C.V30 and I-1 in the Tight eye and 2(^40 and !-2 in
the left eye. Note lh e central fovea I vellowish lesions w ilh
Lent rat black dots and the scattered., small, yellow ish lesions
in tfie paracunlral area (A arid Bj. Angiography revealed л
fluorescent rin^ in the central macular area anti hyperflLio-
rfiscencc of Ihe нгттаИ paracentral lesions IC_".>O ne year later
the patient's vision had deteriorated slightly secondary 1o
cataract;;. The fundi w ere unchanged. The patient died soon
aflur of carcinom a of the liver and lhe eyes were obla]ned for
paLholo^ic ejtnniinaLian. ^ i$ lo p b lh alb ^ c findings in IKu-1iK*11
m acula tl5‘ sbowed focal loss of relinal receptor e le m e n t
and piemen I m itral ion into I be rtilinn in ibe foteal area
Ia n o w lj.. du m pin g oi cells laden w ilb pigmenL and с hono­
red naj adhesion in lhe fovea] area fartitjW 21, □ paracenfral
zone o f thinning of Lhe retina] piemen! ep hb dium '.arrows t
and 4), and locaE diusen (arrow 5]. High-power view erf the
foveolar area i f showed clumps of pwment-fadeti cells and
calcilic body lairowl. NoLu pneservalion of the choriocapLl-
laris anti sligbl thickening of Ibe I nteivapiNarv pillars. Hj^h-
power v ie w of Ivpical diusen i]-. correspond i n^, w itb one of
Lhe STiTnil yellow paractm Ira] lea ions.
G - |: Small parLly faded cenLral lesion fti and H in Lhe
57-year-old daughter of an fl1-yE*ar-old mother iIb bilat­
eral buLterfly pattern of yello w flecks (I and ]>. The daughter's
vihual acuity was 20/40 in (be rfght eye and 20/50 in the Tefl
eye and Lhe molher's was 20/70 in both eyes.
I.A—f fro m L i .iM . '' ■
Croup 3: Reticular Dystrophy of the RPE
3q patients with reticular dystrophy the pattern of yel-
IdW pigment extends into lhe periphery оГ lhe macula
hi a highly organized pattern Lh□L hcii been likened to
со arse, knotted fishnet or сВДщей wire (r'igure 5. ] 2J —
I j и 74,77.66.но,94 development LisuiiIIу begins in the
faveal area. Ihe network gradually extends four or five
disc diameters from lhe macula in all di reel ions. The
net meshes are usually less than one disc diameter in
si^e. The midperipbery and the periphery of the fundus
are unafTecLed early in the disease. The network may be
more apparent angiographicahy than ophthalmoscopi-
tally (i'igure S. I 2HJ. Jt usually fades with age and may be
replaced by extensive atrophic changes in lhe RPB in later
life. Д similar but coarser pigmentary network has been
reported by Mesker and associates."1 Patients with reticu­
lar dystrophy may show an autosomal-recessive as well as
aulosom al-domi nantinheri tance.
i .1 I Variations in pattern dystrophy,
A—C : Fam ily w ith adult vitellifurm luveom acular dystrophy.
The 2K-year-old son ;A ' had mild blurring or' vision in lhe
lighl eye and bilateral, мтла1 lr focal v^teNHorm lesions in lhe
macula. Visual acuity was 20/20 in Lhe right eye and 20/1 5
iin Ihe lt4L eye. Ь lec Iго-ос и Iograph id ratEfls Were 1 .b in bcuh
eyes. rhs 31-ущаг-old mother bad Ь]1а1вщ| bulterfly dystro­
phy (B and С')- Ног visual acu ily was 20/25 In lhe riglil eye
and 20/30 in the left eye. The ST-year-old maternal gjand-
falher had Ы lateral geographic alrophv of lhe КГ-1!: and less
Lhan 20,^200 vision.
0 and E: Kindus pulvemlpnlus type of pattern dystrophy in
a 73-year-old man with mild visual lost of 3 years' dura Lion.
Visual acuiLy was 20/25. He had pruinmenl cel Lc el а г pig­
mentary changes in the periphery.
F —H: Reticular dyslropliy in a young girl with visual acuily of
20/20 in bul-h eyes. Her etec Ino-oculogram and elecLrorelino-
gram We№ flormal: Two siblings had similar findings.
I—L: Fh is 10-year-old maEe com plained of difficulty see­
ing lhe Ы -Setboard. His visual acuily was 20П 5 and 20/20
uncorructod. Bolh retinas show symmoLricaJ appearance of
pDneVcfflHb uf chicken wire-like relicular pal tern dy-slrcjfjliy
(I and |l. The hyperpijjrTienled retinal pijjmenl epbtheEium
showed increased aulofluorescence (Ю- The fovea had a nor­
mal i:onlour w ilh in I act inner segmont-ouler segment junc­
tion IL . lighl eye:-.
Й—Hiг 1л uГ 3>i. L14" S. AniJL-T'-on. l-L, i.uurir.'sy uf ]Jr. S tijli lii o: li'j.:
Croup 4: Multifocal Pattern Dystrophy
Simulating Fundus Flavimaculatus
Some patients develop multiple irregular or iri radiate yel­
low Legions centrally or eccentrical I}1, and in some eases
these дге widely scattered and partly interconnected in a
Lriradiate fashion that may simulate that in fundus. flavi-
maculalus (Slargardl's disease) {Figure 5.13A-H).Lie-1M
Jhese palients. who do not show fluorescein angiographic
evidence of a dark choroid suggesting lipofuscin storage
have heeit recently reported as examples of dominantly
inherited fundus flavimaculatus (see p. 284). Unlike most
patients wilh fundus flavimaeulalus. these patients have
good visual acuity and a more favorable visual prognosis.
I Lowever some of these palients with an exaggerated phe­
notype can show progressive loss of lhe yellow material
and JtETEi/photoreceptor thinning and atrophy resulting
in islands of. or con fluent, geographic atrophy (Figure
Б.] 3). Choroidal neovascular membranes can rarely occur
[E'igure 5.13). Histopathologic and electron microscopic
studies of the eye of a patient with this type of pattern dys­
trophy have demonstrated that the flecks are not caused by
abnormal lipofuscin storage (Figure 5.15C and i l ).Lj0
Croup 5: Coarse Pigment Mottling m the
Macula (Fundus Pufverulentus)
Tallents with fundus pulverulent us typically display mild
visual loss associated wilh a prominent, coarse, puncti-
form molding of the pigmenl epithelium in the central
macular area (Figure 5. ] 2F)-C).,■
,■
' J s ]'his pattern is mosl
often seen in patients with pseudoxanthoma elaslicum in
the author's experience.^'
Allhough Et is convenient to subdivide patients With
pattern dystrophy inlo these five groups, it is important lo
realize lhal lhe fundus findings in some patients do not
fall precisely into one group. Some may show one pattern
in one eye and another pattern in the fellow eye. Olhers
may show one or more eccentric triradiale yellow or da rid у
pigmented lesions. Some may have one or more lesions tn
only one eye early in their course, l'he fundus findings in
patients wilh pattern dystrophy and an asymmetric distri­
bution of triradiale pigment figures must be differentiated
from similar findings Lhal may develop in some patients
wilh recurrent idiopathic central serous chorioretinopathy/
organ transplant retinopathy, and in patients wilh Flschnig
spots caused by hypertensive choroidopathy, e.g., in a
patient with toxemia of pregnancy. [See Chapter 3, Erigures
3.57 and 3.5Й.)
The visual prognosis is good in all subgroups of domi­
nantly inherited pattern dystrophy.15,0'1^ Late geographic
atrophy (Figure 5.111 and K) and choroidal neovascular­
ization may occur in any of the subgroups and are respon­
sible for visual loss. Choroidal neovascularization occurs
э. 12 Pattern dystrophy simulating itmdus
flavimaeulalus.
A-C:"This 5J-year-old wurmin hsd visual at и i tv- bilat­
eral ly. H e r eEeclroreLmograpbEc and eletlra-acLilographic
findings were norm^J; rhere was no family history lor eve?
disease An^io^rams of bolh eves and О ahftwfiq n u bi­
focal slellale bypdfluorescent lesions surrounded by byper-
I iuorescence anti no evidenc^ o f diffuse dampening ol the
background flcmrescence.
D - H : C firicopalhologrc findings in a 51-year-old man w ilb
normal visual acuity and a ■fundus picture nimulalin^ 1un-
r.kis ffavimaculalus. So to the peripheral flecld and lhe nor­
mal a m a ia r c o i of lbe cenlral macular area i.D-F-l. Lif^bt and
electron microscopy rt&tyealed sublie i r d focnil distension
and minor variations in pigmentation of the retinal pigjTtenL
epithelium iRF’t . Occasional cells showed dislended, rela­
tively n o n p ig r n e n d o m e - s h a p e d apices extending above
the adjacent RPE {G and Hi. The KPE did ro t stain w ilh peri­
odic acid—Sc bi if or for acid m ucopolysaccharides. Lied run
microscopy showed that those HPt ceils wiLh distended cylo-
plasm contained tuEjelovesicular membranous material iJ-h.
I-L: A rx^-year-old wom ai: from Trinidad with minc'd heritage
of African, bast Indian, and l-rench presonled with decreased
vis;on in her left eye lo 20y100. Bolh fundi showed exten­
sive iLindub I iavimaculaLus type of patlurn rlysLrophv ея.1end­
ing Eieyond lhe arcades and loss of the vilelliform material in
much cH lbcL lesions. Both maculas showed geographic atro­
phy and I h r lefL, a fchorrisdal neovast ularization in addition
tl). A fluorescein angiogram conlim iud lbe subfoveai choroi­
dal neovascular membrane in lhe tenter oi lhe geographic
alrophy, With increasing flo re s c e n c e in the late frames
fj and K.i. Note lbe absence of a dark choroid and hi*3o of
byperfluorescence around central bEockage from pigmenl^
typical Sf. Itmdus ilavim aculatus Ivpe of pallein dvslnophy.
l'he ri^bl eye hail a simitar appearance withoul lbe choroi­
dal neovascular membrane. 5be received inlravitreal injec­
tions o f bevacizumab every monlb for 4 months followed by
every 2 monlhs for a Lola! of S inj eel ions. Her vision in the
loft eye improved Lo 20''40 and conlinued to remain stable
a I last follow-up 3 years laler. An a и Lo fluorescence ima^infj
shows mcreased autolluorcttcence o f the yellcjw flecks and
decreased auLofluorescence of Lhe alrophic Hot ks :L I.
only infrequently.1<H Class observed il mosl frequently in
patients wilh the solilaiy vilelliform. butterfly pattern, and
lhe exaggerated pattern simulating fundus flavimaeulalus
(Figures 5.1IA-H and 5.121-1.).. 5ome, if not mosl, of the
reports of subretinal neovascularization in fundus flavi-
maculalus probably concern patienls with pattern dyslro-
phy.122 Absence of a dark choroid angiographically and
good visual function suggest paltern dystrophy rather than
fundus flavimaculatus. An occasional cause of Loss of
vision in these patieLils is the development of a macular
hole.1""1 Cass has observed the development of a macular
hole in both eyes of a patient who some years previously
presented with adult-onset foveornacular dystrophy.
 I lislopathologic ebaminalion of two eyes of a patient
with a solitary yellow fovea! lesion bilaterally (Figure
3.J0A-F) showed foca! loss of the retinal receptor ele­
ments and atrophy and partial loss of the fi£PE in lhe
fovea I area of both eyes."1' lhe central pigmented spots
seen biomicroscopically were caused by a clump of large
pigment-Laden celts and extracellular melanin pigment
Eying between lhe retina and Bruch's membrane with
some extension into the ouleT relinal layers. In a ring­
like zone surrounding this centra! pigment clump was a
thick layer of slightly granular, eosinophilic, PA5-positive
material lying between the thinned atrophic KFF and
Bruch's membrane. Fluorescent microscopy showed no
unusual amount of lipofuscin present within the ЙРЁ cells
in this lesion. Bruch's membrane, the dioriocapiliaris. and
j. 13 Complications of pattern dystrophy.
Choroidal neovascular membrane (CNVM).
A - hi: This /З-уеаr-okl V/drrian had a hibLory of soliLaTy vitel-
lil'orm lesions in bolh eyvs And ptmsented with a choruidal
ne£va$cLilar membrane in her lei; uye and a visual dec.-line
Lo 2W 100 (A, B). She undejwenl pholodynamrc therapy
l(i Lhe left eye., which resulted in a disciform star. Fifteen
months lalr'r lhe visjon jn [he right eve dropped Iо 2Q-,40
wiLh increase in the size of Lhe vilelliform lesion and reor­
ganization of Jh(! central pigment I.C:. An angiogram showed
staining o f Ihe yello w material (□ and EJ. Four months laler
her vision dropped Lo 2W 100; she now sbowud evid en ce of
a C N V M with subretinal ikiid and biood (F); An an^io^ram
showed л classic C N V M w ilh lacy appearance early and
late leakage (G and l-t'i. The liLjhl eye also underwent phoLo-
dynamic Lherapy w ilh i'm iled success.

the large choroidal blood vessels underlying the lesion Geographic atrophy.
were within norma! limits, lhe paracentral yellow spots 1—L: This f>.i-year-old m ale presented w ilh a vision of
seen opbtbalmoscopically proved to be typical drusen his- 20/70 in Ihe riyhL and 20/20 in Ihe left eye. Ttiere was a
topathologically (Figure 5.I0I:). small island of gafc^aphic alrophy corresponding lo Lhe
Histopathologic examination of the eyes of two other loss of Ih e yello w pigmenL Fn the foveal lesion (I and jr.
Autcifluoresconcje shows decreased autofluoiesoence consi-s-
patients with almost identical lesions revealed similar
LonL w ilh ioss of reLma' pigment epi I helium (It), lh e left vitel-
findings.'1 1 In one case, however, the eye showed evi­ liform lesion showed hyperauto fluorescence fL.'.
dence of a high concentration of lipofuscin, which may
be responsible for the centra! yellow lesion. 1 A report of
the histopathologic and ultraslruclural findings in two
eyes of a 5] -year-old in an with a pattern of fleets suggest­
ing fundus flavimaculatus and norma! macula and visual
acuity found no evidence of lipofuscin storage or acid
mucopolysaccharide accumulation in the APE - ihese are
characteristic findings in fundus flavimaculalus (Figure
tlevated aggregates of enlarged RFti cells
wilh apices distended by accumulated lipid membranes
with a tubulovesicular appearance Were responsible
for die flecks (]:igure 5.]3C and ][}. 3he findings in this
patient suggest that the yellow flecks in the pattern dys­
trophies. although they clinically appear similar to those
in Slargardl's disease and fundus flavimaculatus, are not
caused by focal lipofuscin storage in the RI>F. ibe same
may prow true in the case of vi tel li form lesions in Best's
disease. Unlike palients with Slargardls disease, patients
wilh Best's disease and aduk-onsel vilelliform foveo-
macular dystrophy do not show the angiographic feature
of obstruction of the normal background choroidal fluo­
rescence (silent choroid] that is caused by diffuse heavy
deposition of lipofuscin material in the RPE.
S Y S T E M IC D IS E A S E S A S S O C IA T E D
W IT H PATTERN D Y S T R O P H Y
Macular changes typical of pattern dystrophy occur in
7 0 % ' of paLients with pseudoxanthoma elasticum (see
Figure 3.38G-L and Chapter 3j. Щ fundus pulverulentus
pattern is most frequently observed, though all йч'е types
of pattern are seenILI: [t-'igure 3.40.J ETattern dystro­
phy has also been observed in patients with myotonic dys­
trophy (1'igure 5. !4), Kj ell in's syndrome (hereditary spastic
paraplegia] (Figure S .IS J QldteiDally inherited mitochon­
dria] myopathies, and one patient xvith McAndle's disease,
a glycogen storage disease in which a deficiency of myo-
phosphorylase inhibits the ability of striated muscle to use
its stored glycogen.]Jfl
M Y O T O N IC D Y S T R O P H Y ____________
Myotonic dystrophia (myotonia atrophica) is a heredo-
famlHal disorder characterized by myotonia, with selec­
tive muscle atrophy baldness, testicular and ovarian
atrophy, premature senility, and cataracts; it is also asso­
ciated in at least 20-2S0i of patienls with some evidence
of retina! degeneration,12'1-1 'v Л variety of funduscopic
pictures have been described, most of which involve the
various forms of the pattern dystrophies, including dark
and yellow spots; stellate [Figure 5J4A -F), butlerily, and
reticular patterns of pigmentation: and drusen (see Figure
E>.]3I-K).[ ■|-EJ|''1 1iU Most patients have minimal loss
of visual acuity, I’igment clumping and yellow flecks in a
j. !4 Pattern dystrophy in patients with myotonic
dystrophy^
A-C: This ^3-year-old man w i]h myoLunit dystrophy had
mild ca La rads, deafness, and pattern dystrophyi Visual acu ­
ity was 20/30. ApplanaLion pressure bilaterally was 6 mrnHg.
Fluorescein angiogram of holh eyes shows halo of hyperfluo-
resrence ground linear lin-rs of hJcickcd fluorescence from
pigment.
D-F lhis -year-old male wilh m yolonk dystrophy had
cataracts in ЬсяЬ eyes. Fundus appoajance in Lhe let") eye
post Calarad remtTval bhows л partial bullerflv type o f pa.L-
Lem dystrophy :LJ), w hich on anglbfltaphy resem tJcs Lhe pre­
vious patient w ith linear blocking by pigment surrounded by
hype-riTdorescenet! (E anti FJ.
triradiate or stonewall configuration have been described
in the peripheral fim dui134^34 Narrowing of the arterioles
may occur. Kurian and Kurns111 found re]iiarkably low
voltage b-waves and subnormal a-waves in these patients,
even when unassociated with any ophthalmoscopically
visible changes. They also demonstrated daik adaptation
abnormalities, l-'oveal densitomeliy changes are frequent
early in asymptomatic patients.111 Ihere is histopathologic
evidence of degeneration of the peripheral retina with
migration of pigment into the retina and some migration
of pigment into the outer plexiform layer in the macular
area.1'' Melanosis and microthrombosis of the peripheral
retinal vessels, together with pigmentary degeneration,
have been described by other authors, bonne authors have
implicated quinine therapy in these patients as the cause
of the fundus changes.
Kj ELL IN 'S S Y N D R O M E
{H E R E D IT A R Y S P A S T IC
P A R A P L E G IA )
Kjel]inr3 syndrome is an autosomal-recessive syndrome
characterised by slowly progressive spastic paraparesis iind
dementia.1'1^ 1'3'* Some of these patients may show evidence
of pattern dystrophy of Lhe retina, most often lhe fundus
fiavin^ajjitija type (i'igure 5.] 5). Ibe flecks seem to be sta­
tionary or very slowly progressive wilh no change noted over
5 years in a patient followed by the author (figure 5.3Г>А, В,
К, and L). The fluorescein angiogram shoe's central block­
age from tbe yellow materia] wilh halo of hyperfluorescence
surrounding this, quite lypical of tbe appearance in isolated
pattern dystrophy.1 Autofluorescence study shows brilliant
fluorescence of lhe material in lhe macula {Hgure 5.15JI
and I ) ' |:; in addition the pigment epithelium shows wide­
spread reticular lype of byperautofluorescence outside lhe
macula (Figure 5.15 H and 3), lhe significance of which is
slill unknown. ЧЪе OCT suggests accumulation of the mate­
ria! wilhin and just anlerior to the ШЧ: [figure 5.1 5J 1 and
|2J. 'lhe flecks and lhe RI4: changes are not associated with
significant visual morbidity, suggesling very slow breakdown
of tbe cells that may be conlribufing towards the accumula­
tion of the yellow material.
Vitelliform lesions similar to pattern dystrophy
have been seen in a variety of maternally inherited
r ¥
L A
j. I j Kj ell in's syndrome (hereditary spastic paraplegia)
and pattern dystrophy.
A lo L: lh is 44-year-old male developed prftdjfcssive ataxia,
.11. 11j i -,.1i ■■
, cr ili' ■11-• ions lilvi\Li's I li- v is j.i :hc lj-
iГу w a i correctable it) 2 ft 20 w ilh refraction- w hen first ™ m -
ined in 2003. Both eyes showed yello w tri radiate flecks,
some w ilh bruwn pigment wilhin Ihem, distributed over Lbe
posterior pole IA and Hf. Fluorescein angiogram showed
central nonl'Viorescence with hi halo of hypedl uoiescence
typical of pattern dy^truphy ( Г -tJ. In 20Qft, autolLuores-
cence imaging showed central increased autofluorescence
corresponding lu iht! brown pigmentation In addlEdti Ihuie
were lattice-like auto fluorescent changes in tbe nasal retina
extending up lo Lhe equator, ihril corrt'spionded !o mild pig­
mentary changus setm on fundus phuKjgiapby lF-[). O ptical
coherence tomography revealed these Lesions as thickening
of Lhe retinal pigment epilhelium (| 1 and E2l. His lesions iind
vision have remained unchanged over more than 7 years LK
artd L i, suf^gestjng lhe condition isaJm osI nortpragjessive.
IA-D, Alsu/c'jnnuj^i.. LawrcnCe J.r the J-Jrfinjl Al I ; l s , Saunders HO ] 0.. B7S-
1 ) - 7 П 2 А - 1 .Т 2 4 ) - 9 г p. I I 2 ).
mitochondrial diseases, including maternally inherited
diabetes and deafness (MTDDJ; mitochondrial myopathy,
encephalopathy lactic acidosisr and stroke-like episodes
[М Ы Л й], myoclonic epilepsy, red ragged fibers (M EftRFJ,
and more widespread pigmentary changes in Kearns-
Sayre, neurogenic muscle weakness, ataxia retinitis pig­
mentosa ( N A R P ) , and Danon disease (see later sections).
M A C U L A R PATTERN D Y S T R O P H Y
IN M1DD, M E LAS, A N D M E R R F
Mitochondrial 15N A is inherited from Lhe mother.
Mltdmonddal defects affect high-energy-utllt/ing organ s
such as the central nervous system, eye, Inner ear., skel­
etal.. and cardiac muscEe. A poiLie. mutation A3243G in
the mitochondrial t>NA causes both M1DD and MLLAS.
Ih e «{act reason why the wme mu tation causes a differ­
ent phenotype Is not completely understood, though there
can be an overlap of findings in. some palients with M IDD
and MLLAS to a variable extent.1,1n Affecled individuals
can fall anywhere in the wide spectrum ofcEinical feature;;,
lhe disease can vary greatly in severity acid features within
a family. 'Itie degree of heteroplasnny (cells contain bolh
muLaled and normal mitochondrial DMA) likely deter­
mines the phenotypic variability between the three syn­
dromes and in Individuals within the same family.
АЛ243С; mitochondria! mutation In individuals is seen
with a wide range of mitochondrial encephalomyopatbles,
including МЁ1АЙ or ^ELAS/MEtUiF overlap syndrome. It
has been postulated that mitochondrial dysfunction causes
a reduction In adenosine triphosphate, which in turn leads
to an Ion imbalance tbit results In death of hair cell and
stria vascularis in the Inner ear. Postmortem histopathologic
examination of the temporal bone of a Woman with M IDD
due to the A3243G mutation has identified diffuse outer hair
cell loss, severe degeneration of the stria vascularis, as well as
a reduction In spira] ganglion cells. Similar histopathologic
findings have been reported In association with lhe A3 243G
mutation In K it LAS, though marked loss of neurons and gli­
osis In the ventral cochlear nuclei were also по||Щ.ш
Macular pattern dystrophy seen In this disease spectrum
has a variable phenotype (figures 5.16 and 5.1 7 ).11: lSi
lhe manitestations can be: grade E: several punctate pig­
ment dots in the macula; grade 11: a butterfly or reticular
patter]! that on fluorescein angiography shows the typical
hyperfluo rescent halo around an area of decreased fluores­
cence; grade Ml: In some eyes mulLifocal or a continuous
perifoveal atrophy of the RPE. 'Itie flecks show increased
autoiluorescence [l-'igure 5.17If] [resembling the pattern
seen in fundus fiavlmaculatus] while the areas of RPH atro­
phy show decreased auto fluorescence (l-'igure- 5.17J and L.).
i.lfr Progression of pattern dystrophy in
maternally inherited diabetes and deafness (MIDDX
mitochondria! myopathy, encephalopathy. Eactic
acidosis^, and strobe-like episodes {M ELA51, and
myoclonic epilepsy, red ragged fibers (MEKRFK
A -F: Tht.1 patient is а 51-уваГ-^И female w ho first presented
ir 2001 w ilh л 5 -year history o f blurred vision w hich she
described as w ind s disappearing w hile reading. Visual acuity
was 2 0/20 both eyes. She was found to tie mutation-positive
Гаг the mitochondrial D N A A 3 2 4 3G mutation, test medical
history included -a 31-tear history of insu in-dt'pendenI dia-
Ejetes, a Ь-уйщг bislorv o f decreased hearing Hind tinnitus, dif­
ficulty w ilh balance, peripheral neuropathy. cardiomyopathy;
weakness, and fatigue. Her mother had diaErctes and dual-
ПЕ5&. The patient's 51 -year-ofd sister had r o diatieles, hearing
loss or eye piobferns and deni м3 other medical problems:
she did not havE! mutation IrcLing. 1bu pa lien Is 29-year-
old son had no history of any systemic problems olher Iban
an appendectom y in lhe past. 1-1is fundus revealed myopic
nerves w ilh normal fundus auCofluorescence. ThE patient^
27-year-old slaughter also had a normal fundus esam anti
autofluorescenc e Eiut did have a hisLory of migraine and
faligue. liolh children w ere found It) he positive for the
A.324.1C mu Lai ion. Нет fundus esarn revealed circumferen­
tial perifoveal islands of atrophy w ilh surrounding pit^nenl
clumping (A and B). There was mild N K D R in both eyes.
Angio^raphv showed w ind ow defects in Lhe area of lhe aLro-
phy, Eiyper fluorescent microaneurysms and blot king defecl
by the subreLinal pigfnent cl Limps (C anti D), Fundus autoflu-
oresc.ence demonstrated decreased aLilol'luorescence in areas
or alrophy with sunoundini^ sfwckled areas ol increased anil
decreased autofluorescence in an area that was Larger I ban
would be expected liy fundus e*am alone '.b and Fj.
G and H: This patient first presen led Гп 1У 96 al the age of 43
w ilh a pigmenLary macular abnormality in bolh eyes wh-i(.h
was diagnosed as a pattern dytlrophy. Vision was 20/20 in
both eyes. Hasl medical history was significant for hearing
Eoss and EinniLus from the age of 25; there was no history of
diabetes. In 2000 aL 47 years of age she had a mild cerebro­
vascular Occident anti later duvxjlofied seizures. D u e lo the
development of additional m edical problems mitochondrial
LDNA testing was performed. The patienl was foLind lo have
Lhe A"!243C mutation. The family history was posilive for a
mother w ith diabetes. The fundus revealed mild mottling of
Lhe retinal pigmenl epithelium with mild pigment с I Limping ii:
Lhe periphery of both eyes; no atrophy was presenL It] and Hi.
 Kath et al.” 6classified M ID D A3243G mutation-associ­
ated macular dystrophy Lnlty.
* Type 1; cci]i Li i i l l o u s or discontinuous peri foveal geo­
graphic atrophy
* type 2: pattern dystrophy with flecks and variable RPH
atrophy.
It appears that Lb€ phenotype changes with age with
increasing geographic atrophy over time.1
i .16 Continued
I—P : This patient firs-t presented in 1934 al the age uf 4b w ilh
d history or paracenlial scotomas Jind difficulty л [J justing lo
changes in lighting. Visual acuity was 2 0 / 2 0 in both eyes.
M edical history was significant lor diabetes of 4 years dura­
tion, rn&uEin-dependent for 2 months. H earing loss began
Lo develop in 1996. Fundus photos in 1994 revealed dr-
nJtttfeгел вй porifovual areas ut geographic atrophy 11 and
|j. There wan significant progression r:*f Lhe macular atrophy
wiLh visual aouiLy of 2Q/.JQ in bolh eyos in 2001 iK and L;.
Fundus autoflLroruscence in 2tK17 reveals decreased a biLo-
I luorescence in areas Ы atrophy with surnoundin^ areas of
speckled auLolluorescence in an а гул larger lhan w ould bo
Expected based on clin ical exam. Fundus auLofluurescence
of ihu patients mother :C3 and IV, whoso fundus appeared
nurmal,. showed subtle moLLiinjj t)f Ihe aLitofltkxracence
in a ti ncum I erenL ial palltiin peri fovea Ily. Inlwestinjilv- the
paLienL's mother's blood Letted negaJive for the A.lIi43C
inilochondrial D M A mu La I ion; no muscle biopsy wab per­
formed. 11 is known LhaL (ho ability to dc4ect Hie mulaLion
i 1 :!ic pcripheiv, he 'd dc -с .. -.i^ person а^ен: : is ■: so
possible Ihis was a new mulation in Lhe parienl herself buL,
lets likeJy ^liven Ihe fundus aulofluonuscence mifiDrmalittfia
in the moLhor. lh e m a tb e also had a Hi-sLtjry (it aduJt-unsel
diabetes Without hearing loss.
[С й |_ 1 г Е « у o l U r . KhitM jI.L K . l ILi .kind I J r . A l j i h H ir d : A - f r o m H i lJn :-,ir;n c;l
ii ■'-1' Й ’r, H - L , Гr u m K u lt i e l j l . l | , : -
5 .17 Pattern dystrophy in maternally inherited
diabetes and deafness (M IDD),
Л -F- Evolulion of relinal lesions in a patient who was
47 years of ajje at firs-L examination (A-C), E in d after 3
yt'ars. of rbJIcnv-up She? carried I hc- rniJochondrial
ГП.3243А i> G mutation, and was previously diagnosed w ith
sprtsOrlrteliral hearing loss and diabetes mellitus. During (ol-
low-up, her v isual acuity remained *Lable (20/40}, although
she experienced subjective central visual loss. Initially, Lhis
patient showed macular and peripapiIlary pijjjnenLary altera­
tions. In the (oven, a vitelliform lesion (A) ^ ilb increased
autofluorescence and some satellite lesions (El were
observed, th e lesion was hypofluorescenl o r angiography,
due lo blbckafte ot" t h e choroidal fluorescence and w h s sur­
rounded by a hyperfluorescent m ildly atrophic zone jC l
Hyperreflective material w as seer between tbe neurosen-
sorw retina and TeLinal pij}nienl epithelium iC2). Throe # №
IЛея, Lhe vitol lifti-rrri material had disappeared leaving a zone
o f chorioretinal atrophy that began to encroach on the fovea
IjJj. This (, horiorelinal atrophy corresponded to markedly
decreased aulolluorescercce. io m e satellite lesions faded,
whereas oLher lesions Ьтчзсате more ртогптеШ in nize iind
irte rsity o f autofluorescence (E^. A hyperfluorescent weLL-
demarcaled w indow defect was seen o r angiography 1F 1>.
О л optics) coherence lomojjrapby, inegular isClenuation of
the photoreceptor-retinal pijjfnenl epithelial Layers was seen
in tbe atrophic area o f lhe previous viLellilorm lesion. The
ouler retinal simetures in the fovea also appeared aboarm ai4
LjliI htili relatively preserved :E2).
G - L : Retinal phenotype o f a 5r>-year-old paLienL, w ho was
asymptomatic and had a visual acuity of 2 0 / 2 0 in both eyes.
A few years previously, diabetes meElilus was diagnosed,
bul no deafness. After 1be mLinal pbcnoLype was diagnosed,
MCDE> was confirmed by Che finding o f lhe m.3243A > С
mitochondria I пиАдОал. O phlhahnoscopy revealed a b rtiid
horseshoe-shaped zone of choriorelinal atrophy LhaL encir­
cled Ihe fovea of [he right eye (G). A less severe appearance
w ilh fovea 1 sparing was neon jn Ihe I cl I eye I Hi. Tbe "(oveal
island" of normal aulorlucjroscence was su*rounded by a
lar^e югъе o f absent autoflkJCreixACe due Lo chorioretinal
alrtiphy. Oulside Lhis atTopbic area, speckled variable auLo-
fluorescence w as roLed 11 and J)4 The angiogram ol the Left
eye shown irregular tiansmission hv|jcrfluorc:sconce ejtcepl
where blocked by pigment (К). Four years later, (be chorio-
nelinal atropby has expanded wiLh gradual narrowing of Lhe
pres^tVfid (oveal area IL:.
IC j d U t t ic y t if D r i C a m i c j l Ь - и н п .'
S T A R G A R D T 'S D IS E A S E (F U N D U S
F L A V IM A C U L A T U S )
In I W J Slargardl described an apparently autosomal-
recessive disorder in seven patlenls from two families wilh
visual lens beginning in the first iwo decades of life, often
wilh a normal fundus, and later associated Tvith macu-
Ear atrophy and yellowish Jeep retinal leeks. ih Kosehr
examined two of Slargardfs original palients 50 years later
and found that Lhey had good peripheral function. In
1U65 b'ranceschelli described similar palients but with
flecks that extended into the peripheral fundus.151 *c'
3ListopaLbologic and histochemical sludies in recent years
have demonstrated evidence lhal these patients have a dif­
fuse lipofuscin storage disease affecting lhe RL*F.'' "]6J
Starga rdf's disease and fundus flavimaeulalus are names
now used interchangeably in the literature Гог what the
author believes are a heterogeneous group of disorders.
Most authors do not restrict the diagnosis of Stargardt's
disease and fundus flavimaculatus lo palients with fluo­
rescein angiographic evidence of lipofuscin storage in the
RPil, although most agree lhal lhe majority of patients
show evidence of il. Ibis author prefers to resLricl the diag­
nosis of Slargardfs disease and fundus flavimaeulalus lo
describe different stages of the same disease in patients
who, early in life, develop a verm i I lion or darkly colored
fundus caused by excessive storage of lipofuscin within
Lbe RPE lhal prevents visualization of choroidal details
( лda rk” с ho roid).] ' J ST-Щ
Patients With Slargardlrs disease, usually during child­
hood or early adulthood, develop visual loss that may be
unassocialed with any evidence of flecks or RPh atrophy
initially (E'igures .i.lS.A and R and 5.ISA and E) but soon
afterward is associated wilh atrophic macular changes
and Lhe appearance of peculiar yellowish RE^ti flecks
(E'igure 5.13G, F, El, and I), lhey appear somewbal simi­
lar to. but should be differentiated from, drusen. These
flecks are variable in size, shape, and distribution. Unlike
drusen, Lhey are less often discretely round, oval, and
j L18 Stargard Vs d isease..
A-С: In 1973 lb iн 1 ^-year-old w hite mart bnd a paiacen-
Lral scoboma. His visual acuity was 2 0 / 2 0 . Except for a deep
orange-red (vermillion) color, lbe fundi w ere normal (Af.
AngiogTriphv dm ioH^tiatm а лнНсп1" choroid and a ring
of 1'ainl hyperfluorescence. In 1391 his visual acuity was
20/200 and m ulliple flecks (CJ were evident.
D - C : This lb-year-old female wiLh unexplained visual loss
and 20/200 vision in bolh eyes was susfjecLed of having a
brain lumor. The fundi appear normal (D j. Neurologic гкд т-
inaLion and skuil rM nlg eftaaram i w ere normal. Angiography
(Ef revealed a fa in I ring of hyperfluorescence in (he central
m acular area and no evid en ce o f obstruction oi Ihe choroi­
dal fluorescence. O ne year later :l-l llie ie were definile* atro­
phic changes in the relinal pigmenl epithelium as w ell as
multiple small flecks in Lbe m acular areas. Angiography (Gf
showed ^neaLer tiyperftuorescence cenlrally and e v idence of
obstrucLi-on o f the choroidal fluorescence elsewhere.
H -L: ForLy-yeai-old miile followed for the pasL 7 years w ilh
20/20 vision in each eye. ExLeiiHive yellow pisejform f[ticks
in the posterior pole of both eyes with islands of geographic
aLrophiy sparing lhe fovea Щ and If. The yelEow flecks
towards 1he periphery are hyperautofluorescenL; I hose Lhal
have ]osL lbe yellow material towards lbe center are h^poau-
Lo fluorescent lhe- itlLinds of KF3t loss are nonaulofLuoTescenl
i| and Kf. GplicaE coherence tomography localises Lbe flecks
Lo lbe neLinal piymtml epithelium fL:.
dome-shaped. When iocaled in lhe midperiphery, they
are oflen arranged in a triradiale or reticular pattern lhat
has been likened lo a forked fishtail. As Lhey begin lo fade,
their color changes from yellow lo gray, partly due to loss
of RLnL substance- and they may appear larger and less dis­
crete. I'luorescein angiography is important in differentiat­
ing Lhe flecks Ln itargardt's disease [fundus flavimaeulalus)
from dmseti. Whereas drusen show a pattern of hyperfluo-
rescence corresponding precisely wilh their si;ie. lhe yellow
flecks Ln fundus flavimaculatus eilher appear nonfluores-
cenL when the lipofuscin is intracellular or show an irreg­
ular pattern of fluorescence with disruption or atrophy of
RJ4i cells (figures 5.13G and 5TE?IL).':,J
RPE
 Most patients ^viLli this disease experience loss of cen­
tral vision first in childhood of young adulthood. Some.,
however, first become symptomatic in midlife or beyond.
I.oss of central vision may he accompanied by symptom­
atic as well as dectropby sic Logic evidence of significant
cone dysfunction.;l: '■|й0 Likewise some patients. particu­
larly Lhose who develop w idespread flecks extending into
the periphery, may develop evidence o f rod j s well as cone
dysfunction.' ' 1 On lhe basis of the fundus and fluorescein
angiographic findings nit lhe time of presenLation, patients
with btargardt's disease can be subdivided into the follow­
ing groups.
Croup 1: VermЩ)on Fundi and Hidden
Choroidal Fluorescence
Some palients with subnormal visual acuity have relatively
normal-appearing fundi except for the easy-to-overlook
heavily pigmented EiPL that in most while patients imparts
a vermillion color and thaL obscures most of the details
of the choroid from view (Figures S. ISA and ti and 5 Д М
and fi). Angiographically lhe retinal vessels are displayed
prominently on a dark background of minimal choroidal
fluorescence, hi some cases lhe retinal capillaries appear to
be more dilated than normal.
Croup 2 : Atrophic Maculopathy with or
without Flecks
In some patients the loss of pigment in the macula may be
so minima! lhal only with angiography can this be dem­
onstrated wilh certainty [Figure 5 .ISh). 'I hese palients and
those in group 1 may be misdiagnosed eilher as having
functional complaints or as having a lesion involving the
optic pathways. Particularly in young children, the flecks
may not be present or may be quite small and limited in
number {figure 5.18K). E.ikewise lhe vermillion fundus
and dark choroid angiographically may not be present in
early life (figure 5.1SL) and E),-M On subsequent follow-
up. flecks as well as evidence of diffuse lipofuscin storage
in the J£FE occur (E'igure 5 .JSF and Cj. Lhe flecks may be
confined lo the macula or may extend into the midperiph-
eiy of the fundi, l he degree and pattern of atrophy of the
RPJ: in the central macular area vary and do not noways
correlate with the degree of visual loss, lhe klfL may show
only mild loss of its normal color, a beaten-metal appear­
ance, or marked geographic atrophy. A diffuse oval or
bull's-eye pattern of atrophy occurs commonly [E'igures
5.] St I and 1and 5.1У)—L.). The lipofuscin within the flecks
accounts for the increased auto fluorescence, which may be
surrounded by regions of decreased auto fluorescence from
the adjacent atrophic KPt. Ihe auto fluorescence pattern
can resemble chronic idiopathic central serous chorioreti­
nopathy. mitochondrial myopathies, and flecks of pat­
tern dystrophy. Patients with fundus flavimaculatus show
a ring of decreased autofluorescence around the disc and
in the fovea, unlike Lhose with mitochondrial myopathies
5.19 Stargardfs disease wilh peripheral flecks (firndus
flavimaculatus).
A—G : D om icShdy от pseudodominandy i nheii Led Slargardt's
disease 1fund lls llavimaculaLus . А 7-year-old girl whose
visual acuity was 20y50 hud verm illion fundi and an^io-
^raphk evidence of ohslruclion c f lh e diorOidal fluores­
cence i.A and P:. She later developed л picture of fundus
flavimacuialus. Ног brother had a verm illion bul other­
wise normal fundus bilaterally w hen he was S years old
(C . Hve years laler he developed I leeks in Lhe m acula and
in id peripheral fundus ль w ell as aftnplty ot the retinal pig­
ment epithlium £RP£J in the macula. W ith in a few weeks
of beanj; examined, lhe brother was Ktfuck in lh e njjht eye
w ilh a dodjjeball. He noled no change in Ihe vjsion hul 2
monLhs laler he had evidence o f a 23-disc diamc'Ler altera-
Lian in lhe h!PL: inferior to the ri^hl macula (arrows, D>. O n e
monLh laler I here was evidence ol SLif>reCinal neovascuJar-
i^aJion, including a small amount of suhrelinal blood and
fibrous mel aplasia and hyjjerplasia c l Lhe К PE. In his lerl eye
temporal tu Lhe т л е й la he had a peculiar paracenLral area
of j^eo^raphic aLrnphy of Lhe Rl-3t similar lo that depk:ted in
Lhe patienl illuslrated in |-L. Anolher 12-year-old brother and
their 30-year-old mother ( i) had mild visual loss associated
w ilh widespread flecks and central PPL atrophy, [here was
no history of previously affecLed generations.
F-H: Ln I his young w om an note lhe unusual IvW areas of
^eo^raphic aLrophy o f Ihe PPL: Ioca Led just temporal Lo Lhe
macula of the left eye (arrows).
I-L: This African Am erican male had a visual acuily of" 20/20
in 1h f ri^hl and 2fiG'D- in lhe lefl eye. Tri radiate yellow flet ks
alon^ w ilh smalli islands of ^ m j^aph ic alrophy were seen in
Lhe macula of bolh eyes (I and fl. The older cenlral lesions
showed decreased aulofluorescence suggesting loss of Lhe
yellow malerial and atrophy of Lhe P5J t, w hile Ih e more
peripheral flecks showed increased aulof iuorescenee from
lhe lipofuscin wiLhin Lhe K F L The areas o f geographic aLro-
phy showed no auLnfluorescencc: IK and L;.
lA - t, c i k j M l'w l iI JJr . L i.ir y L h is h i l- L , сиигкчу n f [.lr . I i r t i c i f . J l u v . i
where Lhis pattern is absent {Figure 5.1 SJ and k). Patients
wilh the bull's-eye change may initially be seen with nor­
mal visual acuity and a ring scoLoina. A few such patients
retain 20/20 visual acuily unLil 40 years of age or beyond
[figure 5.20C-L). Varying degrees of atrophy of the KPL
surround and extend beuveen the flecks, lhis is always
more evident angiographically than bionncroscopically
[E'igure 5.191!]. If the number of leeks and amount of
Щ?Е atrophy are great, the angiographic dark choroid sign
typical of Slargandt's disease may not be evident in Lhe
posterior fundus, although it is often preserved in the peri­
papillary area, lhe oplic disc and retinal vessels in patients
in groups ] and 2 are normal.
Patients wilh widespread flecks may develop in one or
occasionally both eyes an eccentric well4lefined zone of
reactive RPE changes that includes hypertrophy, hyper­
plasia, fibrous metaplasia, and atrophy (E'igure 5. PJD ).
Palients wilh many flecks occasionally develop subreti­
nal neovascularization and disciform detachment of Lhe
macula.1-2-1^ 1^
 Color vision testing usually shows a mild red-green dys-
chromatopsia. Many patients show a prolongation in rod
dark adaptation and selective prolongation of the la ter seg­
ment of rod recovery.1 ■'^K-leclroret biographic find­
ings are usually normal or slightly disturbed. The hOG is
subnormal in ю т е cases. Some patterns may develop pho­
tophobia, loss of color vision, and eiectroreti nograp hie
evidence of a cone dystrophy.
Croup 3 : Atrophic Maculopathy with
Late Signs and Symptoms of Retinitis
Pigmentosa
Patients in group 3 are similar to those Ln group 2 but in
addition show signs and symptoms of retinitis pigmen­
tosa, including nyctalopia, diffuse lots of pigment from
the Шзе;, narrowing of (he retinal vesselsr and abnormali­
ties of both thescotopic and pholopic ERC.US
Croup 4: Hecks not Associated with
Macular Atrophy
Patients may have paracentral and central flecks associated
wilh minima] bio microscopic and angiographic evidence
of atrophy of the RPli between the flecks. Visual acuity
may be normal if the center of the Ebvea is not involved
by a fleck. Most patients with a large fleck in the foveola
have subnormal acuity. Fluorescein angiography shows a
dark choroid, obstruction of the background fluorescence
by tbe flecks with minimal hyperfluorescence in a small
area immediately surrounding tbe flecks. In the absence
of mformation concerning other family members, and
in eyes showing borderline evidence of a dark choroid..
El may be difficult or impossible to differentiate some
patients in group 4 front patients with dominantly inher­
ited pattern dystrophy.'^1,|5ы
Whereas the fundus findings and the degree and rale
of visual loss are usually symmetric, the atrophic changes
and visual loss in some patients may be more advanced
in one eye. in general, the onset, rate., and severity of
visual loss are similar in family members, bu( notable
exceptions to this rule occur. In an appraisal of visual
loss with age by both life-table analysis and cross-sec-
Lional procedures in У5 patients wilh Stargardtrs disease,
5.2(j Exte n sive fl e с ks о f fund us flavi macn Ealus,
A-F: Г1тis 30-vuar-oid Ща1й had extensive frivol vemenl or the
fundus in both t'yus evlending almost to Lhe equator A-D:.
Note Сhe decreased Э1ИйЙ1(огйевпее rn mosl uf the lesions
EfKct'pl the very anterior onus that show (frapased auto fluo­
rescence, signifying progressive atrophy oJ (he netins I pig­
ment epilhelium cells and loss of tbelr lipofuscin content (E
and Fi. His visual acuity was count lingers in Lhe fight and
20/30 in Ihe left [*уе.
Evolution of flecks in fundus tlavimaculatus and
normal vision.
G-L; This 21-year-old young male was asymptomatic in
2004 and Ihe flecks were discovered on н rouline examina­
tion [(jr glasses. He had a vemiillion fundus without visible
choroidal vessels in Ihe posterior pole and yellow flecks,
ноте with central pigmentation in Ihe superior тлей la and
superior to the disc (G and H). The red-free images better
delineate 1he flecltfi.
I and J: Five years laler there was a significant increase in the
flecks now distributed all over the posterior pole and nasal
to the disc in both eyes (K and Ц His visual acuity was slill
20/20 in each eye.
iA-]-, ci iurlL'1-уii| U r . I-мпси U«cLhi.t and Ur. •■
!■
■I г.■
1’ishman and associates found the probability of main­
lin in g a visual acuily of 20/40 or better in at least one
eye was 52% by age \9 yeait -, 32% by age 29 ye ait -, and
22% by age 39 years.1 lhe visual acuily after reaching a
level of 20/40 tended to decrease rapidly and stabilize al
20/200. l.ow-vision correclion in these palients is highly
successful.1'*'-1^
"lhe re is considerable evidence that Slargardl's disease
and fundus flavimaculalus are the same disease and thal
(be latler probably represents a more advanced and wide­
spread stage of lipofuscin storage and ЙРЕ damage [Figure
5.14A-K). I"he age of onset of visual loss and the severity
of visual loss are generally greater in patients with wide­
spread flecks [fundus flavimaculatusj.11"1 The eleclro-
oculograpbic and eiectroreti nographic findings are more
likely to be subnormal in patienls who either have or are
destined to develop widespread flecks in the fundi and
other signs and symptoms of a more widespread lapeto-
retinal dystrophy. ^ 'lhe eleclrophysiologic studies
therefore are probably of sonte prognostic value, particu­
larly itt younger palients who have only minimal flecks.
 I LLsKjpлthologic examination reveals Lhal the RE’Ei cells
posterior to the- equator л re enlarged and densely packed
with an intensely E1AS-positive substance with ultra-
slructural,. auto flu orescent, and hislocbemical properties
consistent with an abnormal form of lipotuscin (I'igure
5.2L).1 " ihe greatest concentration of this lipopig-
ment is located in the posterior fundus. Scanning electron
microscopy has shown evidence that focal areas of marked
hypertrophy of ftPt cells, as ^velE as aggregates of cells
containing lipofuscin., зге responsible for the nonfluores-
cenL yellow flecks {figure 5.211 and f ).1'*" lt'° E:igure 5.21
(Ei-C;) illustrates the typical light microscopic changes (haL
occurred in one eye in each of two sisters wilh identical
changes of geographic atrophy of the RPE associated With
macular flecks characteristic of itargardfs disease. En an
eye of a 16-month-old to y with incipient Starga rdf's dis­
ease the НГК cells were less distended with lipofuscin and
at 5 years of age his remaining eye showed angiographi­
cally a dark choroid that was confined la the posterior fun­
dus.'"' This observation and the angiographic changes in
the child illustrated in figure 5.1Й are in keeping
with the concept that the lipofuscin storage disorder of
the RPE is an ongoing process and may not be clinically
detectable in Lhe early years of life ."'1 Ilirnbach et al. have
suggested that dll-tnhs retinol dehvdrogenaser a photo­
receptor outer-segment enzyme, may be defective in these
patients.'1*1
l'he marked engorgement and hypertrophy of the ElPli
cells with lipofuscin in patients with widespread decks
appear it) predispose them to development of one or more
local patches of reactive and hypertrophic changes in the
RPE [figure 5.11Ю]. The author has seen these RPH lesions
in association with fundus flavimaculatus in eight patients.
In al Least one patient they were observed to develop fol­
lowing a blow to the head with a dodgeball (figure
5.PJD ). Ihus RL3L engorgement with lipofuscin may pre­
dispose patients with fundus flavimaculatus to ouler
retinal damage in the event of a contusion injury. Al the
19У5 Retinal Society Meeting D r. Richard О her reported
a palLcnl with fundus flavimaculatus who sustained
hlunl trauma and lierlill's edema that was confined lo
the macular region Ln an eye with the typical appearance
of fundus flavimaculatus. Several weeks later the patient
developed widespread degenerative changes of the RPli
and subretinal fibrosis in the injured eye. Del Buey et a f
have reported similar severe d egen erative changes develop­
ing rapidly in association with fundus flavimaculatus in a
young girl struck in the: eye with a cork.'"
In most patients who show clinical evidence of lipofus­
cin storage fundus flavimaculatus is inherited as an auto­
somal-recessive trait. A similar phenotype, however, occurs
En some families showing evidence of dominant inheri­
tance [E:igure S.19A-^J. 1,! The author has seen only
one such family, and because only involvement of two
Ь.2 [ С Iinicopal hologic find ings rn Starga rdl rs disease.
Д and B: Progression of geographic alropfiy over a 9 -year
period in a palicnl w ilh Stairiteftft's disease.
Youn^ wom an w ilh SLargamlIгн disease Hind large area of
geographic atrophy o f Lhe reLinaE pigjTtenL epithelium IRPE^.
NoLe flocks near Ihe edge of the c e n ta l legion. Her sisLer,
who had identical findings, died of cancer and her eyes were
oLilainud ar aulopsy.
D —G : Histopalhology o f SLargardt's disease in Lhe srsler
of Ihe patient illuslraLud in Cl. LJulh sislers had geographic
atrophy of Lhe KFfc wiLh supjuu-ndirW Hecks- in l'he m acular
area ophlhalm oscopicaliv £t-T Note Lhe enlarged KF’fc ceils
i i l" r^o1 wiLh lipoluM in in : K : pus1jjrior fundus
ID); 1Еъе positive staining of Ehe КИЕ w ilh periodic acid-Schiff
IPAS'- (jgg lhe loss o f 1f>e ouLef retinal layw s and FilJ t i|arr*j(VYs:-
in Lhe central m acular area (H j; and Ihe near-norma I appear­
ance of lhe Rf3t near the equaLor (Gj.
H —|: Scanning electron microscopy (II and lighl micros­
copy If) of lhi> eye removed from a 2-t-year-oid man With
widespread flecks 'ifund-us ffavimaculalusl in lhe fundi fH
revealed lha) the Ilucks w ere causer! J?y focal hfyperLrophy
of lhe КГЕ: cells lhal are d islender! with an intensely KAS-
[josit-ive, granular, autofluorescenl substance wiLh lhe proper­
ties of an abnormal form of lipofLiscin.
K: Diffusely hypertrophic RL3t w ilh KAS-posiLive granules^
in lbe posterior pole (above}; where Lhere are nnwe K P t
melanosomes, compared Lo Ihe periphery w ilh few er KF3fc
melanosomes.
I C - G . c u U h t e s y O l I J r . K c b i - r l P . V h iL V L ir : H - f f jo m u l , l I. K " ; K,
L'LJurLe^.v' I IJr . k ,il|jh C . ! .isi"hr I г
successive generations was demonstrated, the inheritance
may be recessive rather lhan dominant (f igure 5.1UA-G).
In families ivith dominantly inherited fundus flavimacula-
tus, gene mutations have been mapped lo the short arm of
chromosome 1 and to chromosome I3q34.|Ч” 192 Linkage
lo chromosome 6q has also been established.-113 'l'he
patients in this latter family did not show angiographic
evidence of lipofuscin storage. The author believes lhal
patienls wilh a fundus flavimaculatus-like distribution of
flecks, absence of a dark choroid, autosomal-dominant
inheritance, and generally a more favorable visual progno­
sis are more appropriately classified as having pattern dys­
trophy rather than Stajgardfs disease. lJkewise, the author
prefers Lo classify recessively inherited alFophic macular
dystrophies in patients without flecks and without a dark
choroid as "unclassified'' rather lhan Starg^rdt's disease.lM
Pattern dystrophy is not Lbe only disorder that may
simulate fundus flavimaeulalus. A similar pattern of flecks
may develop within weeks or several months In one or
both eyes of patients with idiopathic uveal effusion (see
chapter 3), diffuse bilateral uveal melanocytic prolifera­
tion |see chapter 13], renal or other organ transplantation
and chronic central serous chorioretinopathy (see chapter
3), collagen vascular disease (see chapler 3), and large cell
lymphoma (see chapter 13). Яг‘
A UTO SO M ALD O M 1N A N T
C EN TRAL A R EO LA R
C H O R IO R E T IN A L D Y S T R O P H Y
U N A S S O C IA T E D W IT H D R U S E N
O R FLEC K S
]"hLs dystrophy is characterized by the development of
fine, mottled depigmenlation in the macular region.. usu­
ally in late childhood or early adulthood in the absence
of any symptomii (Figure S.22.\ B, G. and 11). Visual acu­
ity, visual fields, FRG, and dark adaptation art normal
early Ln the course. Multifocal FKG shows abnormal cen­
tral function anti late stages may sometimes show more
widespread cone and rod d y s f u n c t i o n . The HOG
may be subnormal. Fluorescein angiography is helpful in
detecting the earliest pigmentary changes of the macular
region that may eventually have a bull's-eye configura­
tion (Figure 5.22B, I, and J). Associated wilh the gradual
development of symmetric, sharply outlined, bull's-Eye
oval or round areas of geographic atrophy of the RPE in
the macula in the absence of any flecks or drusen there is
slow, mild deterioration of visuat acuily during the fourth
and fifth decades of life (Figure 5.22C l:, G, and li). The
tindings can Ье staged from I lo 4 (Figure 5.23). Families
wilh earlier age of onset of visual acuity changes (Figure
5.22G-]) are known.1"' lhe area of geographic depigmett-
tation of the R P t enlarges concentrically but usually does
nol exceed three lo four disc diameter;;. In some patients
geographic atrophy of the RFli in the peripapillary region
accompanies the macular changes As the patient lives
beyond the fifth decade, the reddish orange color of the
Lii'lv d ’.-.-i'oLda] u-ssds wiliiiu ::il' .mv. H \l\:i. лI I'-iphv is
replaced by a color (Figure 5.22F К and L).
Serous and hemorrhagic disciform detachment occurs
rarely, if al alE. Visual acuity in the range of 20/100- 20/20t}
may he retained even during (he seven ih and eighth
decades of life. The optic disc, retinal vessels, and R P t out­
side the macular area are usually normal in appearance.
"-.21! Autoso т а I-dom i nan t ce ntral a reo larch oro i dal
and retinal pigment epithelium (RPE) dystrophy
unassociated with drusen or tlecfcs.
Л nnd B: A 19-year-uld buy with visual acuily Ы 20/15
had minimal changes in the K P t centrally. Angiography :13
revoked delinile evidence of pig merit loss in lhe m acula.
С—E: The 4 (j-year-о Id lather o f patient ir A had visual acu ­
ity of 2Q/70. H e had a central scotoma corresponding lo dis­
crete агёай a l FIE’L й1фрЬу Eji laterally |'C)j Arleriovonous-sLii^e
angiogjani showed delay in perfusion of lhe large and small
choroidal №sbe3s cenlrally ■L.JI. Approximately 20 minutes
after injeclion, the angiogram showed choroidal staining that
was mosl marked m Ihe periphery of the cenlral esion lb'.
F: The 74-year-old palernal grandlather of Lhe palient in A.
Note whitening of Lhe lar^ge choroidal vessel walls. His acu ­
ity №15 20/100. The palient illustrated in A had tw o affected
siblings, l he p a tie n t illustraled in Л and C- had modoralely
abnormal electro-oculographic findings. Their и lectroreli no­
graphic findings w ere normal. Several members of Lhis Fam­
ily a ho have von Hippel-Lindau disease.
C —|: This healthy 13-year-old wom an had 2(У15 visual acu ­
ity in both eye^; There was mottled depigmenlation ol the
pigment epilbelium and mauled 1турег1 luorescence m the
fihaculaГ: area bilalerally. Нет oleclio-acLilogfam, eleclnoret-
inograin, anti 100-hue color vision lest resulLs wore normal.
Three si filings had n^acular degeneralion.
К and L: The 46-year-old mother o f Ihe palient in G-l noled
visuat loss beginning al age 24 years. H e r visual acu ily was
10/200 Ejilaterally. The rod and cone eleclroreLinujjjam and
electro-oculogram findings w ere moderately abnormal. This
patient's mother, Iw o malernal aunts.. Lwo maternal uncles^
and maternal grandmother had m acular degenrtra ti on.
initially, a relative (but later an absolute) central sco­
toma corresponding to the area of JJPL atrophy can be
demonstrated. Peripheral fields are normal. Fluorescein
angiography demonstrates varying degrees of loss of lhe
choriocapi Haris within the area of KPL atrophy that cor­
relates well wilh the degree of loss of visual function.
There usually is minimal evidence of atrophy of the large
choroidal vessels throughout the course of the disease.
(
 Dominantly inherited central areolar chorioretinal
dystrophy unassocialed wilh fecks occurs infrequently
and has been confused in the Literature with a variety of
other more prevalent diseases Associated with geographic
atrophy of the КЕЧ:. Central areolar or geographic atro­
phy of the RPli and choroid is a nonspecific change that
may occur in association with other diseases, including:
( 1 ) familial macular dystrophies associated wilh macular
coloboma; ( 2) central areolar RPE dystrophy1"" that may
he the same disease as (1); (3 ) dominant macular drusen
associated with senile macular degeneration and disciform
detachment (see figure 3.46); (4) basal laminar drusen;
(5) autosomal-recessive macular dystrophy associated
wilh Stargardl's disease or fundus tlavimaculatus (Liguies
5.13 and 5. « ) ; (* ) central areolar atrophy in the cone
and rod-cone dystrophies (figure 5.] 6); (7) central areo-
Ear atrophy secondary to myopic degeneration (see Figure
3.34); and (a] central areolar choroidal and RE’Ei atrophy
secondary to serous or hemorrhagic disciform detach­
ment of the EiPt and retina from a variety of causes, such
as idiopathic central serous chorioretinopathy or choroi-
ditis.:i”1 Autosomal-dominant central areolar choroidal
dystrophy may also be confused with other disorders lhaL
cause a bull's-eye pattern of pigment epithelial atrophy
(see benign concentric annular macular dystrophy, p. 300,
and chloroquine and hydroxychloroquine toxicity).
In J953 Sorstjy and Crick described five pedigrees of
patients wilh "central areolar chon)idal sclerosis " Only
one or possibly two families had evidence of dominant
inheritance.'41 Several patients showed evidence of flecks
or drusen and may have had either Staigardfs disease or
senile macular degeneration. Histopathologic exa mi nation
of one patient showed evidence of choroidal and RPE atro­
phy but no evidence of sclerosis of the choroidal vessels"0J
A family of three successive generations of patients
wilh central areolar macular dystrophy seen in Miami
also have autosomally dominantly inherited von Hippel-
l.indau disease {Vigurc 5.22A-L'). Wansour reported three
brothers, each affected wilh central areolar choroidal dys-
Lrophy and pseudochondropEaslic spondyloepiphyseal
dysplasia, both of which are heterogeneous disorders
wilh autosomal transmission.''1 The association of two
rare diseases having an autosomaL-doniinanf inheritance
(germ cell mosaicism in one parent) or autosomal-reces­
sive inheritance resulting from parental or grand pa ren­
tal consanguinity (new syndrome) is more likely to be a
true association than a simple coincidence. '' Mutation
in the peripherin/tfJJS gene on chromosome 6 is the most
common cause of autosomal-dominant central areolar
choroidal dystrophy, though the disease is genetically het­
erogeneous. 113i20-1 Five different mutations have so far
been found, the commonest being arginine 19!> Eeucine
b .'Jl Stages of centraE areolar choroid a! dystrophy,
A—С : Stage 1 central areolar choroidal dystrophy (CACD>
in a i^-year-o Id asym plom atic patient with a visual acuity
of 20/'2£). ih e carried л p.Argl42Trp missense mutalion in
Lhe ркЙ Н 2 gene. 1L>d fundus photograph shows parafoveal
zones of hypopigmenLaLion -A), w hich correspond to areas
о: increas'd .luLolluorusci'n- с 15. Spot Ir-i i-dr n i.iii: ;ip t k jl
coherence tomography iC X U l horiJ® ntally Ihroujjh LheKe
zones jusL below the Fovea shows disorganization and lhick-
□r:in^ of lhe; ou1ermost neuroretinal layers, aL Ihe level o f Ihe
pholorecepLor outer segments LLl.
D-F: Stage 2
CACLJ. in a 60-year-old patienl with a visu.il
acuity I 20/20 ip.Ar$142Trp mulationi- She com ­
plained of mild micropsia. A hnildly alrophic hypopiцпшmud
oval area was. seen in Lhe m acula iLJ). lhe lesion was fainlly
byperfluorescent on fluoresceEn angiography. Fundus auto­
fluorescence showed an uvaE lesion wiLh granular areas of
decreased auLofluorescence anti a lew spols ot increased
autofluonescencr? HEj. In early stage 2 CACD, speckled areas
ol increased autofluorescence predominate, A horizontal
spectral-domain O C T scan through LhEs lesion showed an
accumul alion of hypeireffcctive m alenal L in d e r lhe fovea^
between Ihe neurosensory retina and retinal pigment epithe-
I !Li in. This hyperreflective material m ay correspond I о clum p­
ing of aJlercd photoreceptor ouler segments. OLilside Lhis
area was disruption of photoreceptor Jayer with some byper-
rufl'jc. live spots that m a v c o rre s p o n d Lo t lum p s ot" a Lm o rm a l
p h o lo re c o p Lo r o u Ie r-s e ym e n t m a le ria l ( R .
С - 4 : ^lage 3 C A C t J , in a 4 7 -y e a r -o ld paLionL w h o also
carried ,i р . А г ^ М Л т р n iu la tio n in the P f\ FH2 g e n e . Th e
visual a c u ily w a s 2 0 / 2 5 , a n d lh e p a lie n l re p o rte d a m ild
decrease m visual a c u ilv A n a re a ol" w e ll-d e m a rc a te d
c h o rio re lin a l a tro p h y w a s se e n jusl o u ts id e lh e fo vea I
cc n le r i G ) . O n fu n d u s a u to flu o re s c e n c e , Lhis a tro p h ic area
s h o w e d an a b s e n c e ol" a u tQ lT u o re s c c n c e . t> u ts id e this, the
m o re m ild ly a fleeted a re a s h o w n d LjTanular /tin e s o f a lte re d
fiuLolTu urescen ce a h o r iz o n ta l s p e c ira l-d o m a tri О Г Г
scan, lhis arua o f с h o rio ru lin a l a lro fih y c o fre ^ p o m ie d to a
Lh in n itij; o f Lhe o u te r n e u ro re Lin a l layitirs, ynrirkud A tte n u a tio n
oE Lhe p ii{ )L o m :e p to r ia ver, his w e ll а к an a U c n u a le d retinal
p ig m e n t e p ilh e liu m layer. O u ts id e this a re a r ih e s e structures
w e re m o re rhiildly d is o r^ a n ize rl a n d a Men и a Hid iLj.
I- L: Sta^e 4 CACILJ, in a 49-yuar-oJd patr-unL with a visual
acuity o f 20/200 (p.Argl42Trp mutation in FR FH 2 ).
OphthaMhSsDopy showed a w ell-circum icribed are;i of pro­
found chorjoreLinaJ atrupliy lhal invtblved Ihe fovea, w ilh
some pigmenl clumping (Jf. Tin is atrophy ajjain corresponded
to an aL)stjnce cjr" fundus auLollutjrescence. Sam e residual
increased a и Lo l! иог-escence was seen at the border of the
Eesion (K.l. O n fluorescein angiography, the choroidal vessels
were visible through th« relinal pi^ n en t epilhelral w in flo w
defect. The Eiorder of the lesion showed some staining ll...
It 'иигГту Ы Ur. <J,;nhirj| Hiiim.J
BASAL LAMINAR DRUSEN
ASSOCIATED WITH TYPE
II MESANGIOCAPILLARY
(MEMBRANOPROL1FERATIVE)
GLOMERULONEPHRITIS
Mesan^dcapiUaljf glome rulonephrilis (MCGN.. KipGbl) is
а renal disorder characterized by proliferation of mesan-
glal cells acid alterations in die basement mem bra ne of
the g!omeru]us.'u',-JI4 MCGN has been classified on the
basis of lhe localization and composition of the glomer­
ular deposils: lype ] With subendolhelial etectron-dense
deposits along the glomerular basement membrane with
presence of complement and immunoglobulin within the
glomerulus, type 19 with electron-dense ribbon like depos­
its of C3 in the lamina densa of the glomerular basement
membrane without the presence of immunoglobulin [also
called dense deposit disease), and type III with deposits
Eike those of bolh types E and II. and bolh subepilhelial
and subendothelial location. Other associated features of
the disease Include chronic hypocomplementemia.. partial
Eipodyslrophy, and a higher incidence of diabetes. Type 3
is twice as common as type II and is less severe. 'lVpe 91
usually begins in childhood or early adulthood and
tends lo be a progressive unremitting disease., often recur­
ring even after renal transplantation. M l’CN comprises
approximately 4-7^-ii of palients with idiopathic nephrotic
syndrome. Basal laminar drusen and larger more typical
drusen occur frequently in the macular region of patients
wilh lype 19 MCGN {Jrigure Б.2^А-Н).-0Г~-''1 'Ihe num­
ber of deposits increases in number and size with age
and duration of the disorder.11" Although mosl patients
are visually asymptomatic, some may develop choroidal
neovascularization al an early age.'" x lbe fundus find­
ings occur more frequently in those palienls with type EE
MCGN who have in addition partial lipodystrophy.307
I hose patients who have undergone renal transplant may
develop signs of organ transplant retinopalhy with exuda­
tive retinal detachment, relinal pigment epithelial mot­
tling, or serous pigment epithelial detachmeiit5JL>," 'h
which may alter the fundus appearance. EJgbl ^nd eleclron
j.24 Cuticular and taicil'itid drusen in palients wilh
type 11 membranoproliferatlve glomerulonephritis
(M1>GNL
A—D: A 5Q-year-ol[I man, who had a history of renal trans­
plant rU ages .36 and 39 years because of type lj MIJGN.
complained of blurred vision of 2 months' dur.ilion. Visual
ncuilv in ri[ihl eye was 20/200.. iefl eye 20/20. Nole variabil­
ity of the size of the drusen, some of which appear calcified.
АпцiciijTiiphv revealed culicular drusen (C and EDf.
E and F: A 19-year-old man with childhood onset diabe­
tes- and nephftrtfid syndTome associaLctd with tvpe II MPGN.
Visual acuily in (he rijjhl uye was 20/20 and of lhe left
eye w;ls 20/25. hvole dust№ of liny basal laminar drusen
ia mows I and ini Id background diabetic rellnopalhv.
Radial basal laminar drusen imaEallia levantiiKsejL
G —L: An iv| v"-.4-i i d 1 ч :: .i-i.ir i: . ilf Ironi li'iiri'- sci- i ..чи::'
a diagnosis o f age-related macular degeneration from age 40
onwards. H is visual acuity W at 20/400 in each eye. H e had
т(я1ета1е CH^Iarads. Kodufar drusen wore distributed in lhe
macula and nasal lo lhe disc. The fovea showed extracellu­
lar pigment ,ind atrophy. The Lemporal drusen w ere smaller
and arranged in a radial fashion. He also had evidence of an
old s-uperoleniporal branch relinal vein occlusion IG and H..
H i5 4S-year-old daughter accom panied him and was ехапэ-
ined. Her visual acuity was 20/50 in the fight and 20/00 in
lhe left eye. IJolh jjtjweas showed cenlral fibrosis 5ИгтйЦ1псЫ
by several small drtlsfin lhal had a radial arrangement tempo­
rally and w ere also seen nasal to the disc (I and Jj. The radial
anangem onl is more distinct on lhe ned-Fruo images ■.К I; lhe
angiogram of Ihe right eye shows lale staining of the central
fibrosis (L). They had no relatives in Switzerland but Ih e Fam­
ily could be Iraced back Lo the L-K.
microscopic study in one patient with drusen revealed
diffuse and focal deposits in the basement membrane of
the IJE’b si ini Iar to those found in the glomerulus."0' 'E he
nature of these deposits was nol determined.
A variety of mutations in the complement factor IE
(C fH ) gene are seen in a minorily of palients wilh W PGN
LE. Homozygous or compound heterozygous Cf:H muta­
tions result in lack of plasma C 1:1 E. causing uncontrolled
alternate complement pathway activation resulling in
ubiquitous G3 deposition in the bruch's membrane and
glomerulus.-'■ Jl9
D O M IN A N T L Y IN H E R IT E D
R A D IA L B A S A L L A M IN A R D R U S E N
{M A L A T T IA LEV A N T IN ESE,
D O Y N E 'S H O N E Y C O M B M A C U L A R
D YSTRO PH Y)
A dominantly inherited disorder characterized by a radial
pattern of Innumerable, small, elongated basal lami­
nar drusen was in Hi all у reported in a family from the
I.evantine valley in ^tti^erlaiidJ120' 22^ И was later found
that the condition; is the same as the dominantly inher­
ited honeycomb retinal dystrophy described by Doyne in
1В99.Л ' Typically the radiating pattern is most prominent
in the temporal macular area and is often accompanied
by larger nodular, and at Limes papillary, drusen and vari­
able amounts of irregular subrelinal fibrous metaplasia
and hyperplasia of lhe RPE (I'igure 5.24CI-JJ. Ibis subreLi-
nal scar tissue may or may not be vascularized. 'ВДв visual
acuity is often excellent in spite of the fibrous metaplaslic
changes, lhe radial drusen demonstrate early discrete flu­
orescence similar Lo that of basal Laminar drusen (ligure
5.25 В, C, F, and J). On indocyanine green angiography
the lesions mask the fluorescence early, and Lhe central
drusen stains late with hypofluorescence of its edge.226
i Iigh-resolution OCT shows conical deposits between the
RPE and the Bruch's membrane, and late stages second­
ary disruption of the outer nuclear layer......choroidal
neovascularization is known lo occur and responds lo
surgical removal photodynamic therapy, and antivascu-
Ear endoLhelial growth factor antibod ies.22*JJ0 Streicher
and Krcmery' " and l>usek and associates' 12 have reported
a dominantly inherited pedigree of patients with radial
basal laminar drusen. Even though the typical appearance
is of nodular drusen that fill the macula and often the
area nasal to the disc, phenotypic heterogeneity is seen in
some families, showing less extensive drusen or predomi­
nant fibrous change rather than drusen (I'igure 5.2GLand
Mutation in the EFEM Pl gene (Arg345'E'rp) is
responsible for the conditio n.'""1 : '" 'I here has been a fam­
ily diagnosed clinically as malattia levantinese, without the
5.25 RadiaE basal laminar drusen ^malattia
levanlmeteh
Д-C: A 31-vear-o Iti man complained Of m'eti^morpbop-
sia of 4 m onths dura ILon. His family hislory w;ls negalive.
Visual acuily in Il:e lighl eye Was J l V l . 1» and in 1h^ Iem'I eye?
was 2Q/40. A radial pisllern of drusen and subrelinal star­
ring w ere present in both eyes |A1. Angiograms in bolh eyes
r e e l e d a similar rudinl pistlern of drusen LhaL i kioresced
during lhe early arteriovenous- phase LE3 and Cj. Ther>j was
evidence ol subrelinal neovascularization rn lhe Iel L eyelE^.
D-F: К ad i□I drusen in a 4Д-уна r-ol d wom an w ilh a 10-year
history of poor dark adaplation and .1 1-year hisl cjry ol
blurred vision. Her brother had similar visual complaints and
her mol lief and mnlernaf grandm other were legally blind
because of ma-cular degeneration. Ih e palienL's Viwai acuity
was 211/.Ю liLjhl eye and 2 El/70 LefL eye. Note Ihe prom in m l
nudulaLion and evidence of calc if Feat ion of Lhe cenlral dru­
sen in □.
G-l: kadial pattern of drusen in a 43-year-old 'л о т an whose
family history wan negative. Visual acurty was 20/40 in Lhe
righl eye anti counling finders in lh e lei 11 eve. N o le hyperpla-s-
Li( relinal pigmenL epithelium i KFE j stars in bolh eyes.
J and K: HisLofjathology [ and K, electron micnographic find­
ings o f largE rvm ILi nodular and papillary basal Jaminar drusen
Iarrows I in patient w ilh dom inanlly inheriled radial dfusen.
NoLo Ihe papillary lhickenin>j of lhe basal Lankina I3JL' o f Lhe
f£FE in k.. Com pare w ilh Lhe pnominenlly elevaLc’d drusen in
G. Note loss erf retinal receptors and subretinal fibrous meta­
plasia in ).
il . i n d (ru m L ju s i- k i :1 ,l1. " " '" I
Arg345Trp mutation, suggesting other gene defects iflay
also cause this phenotype. "1' L.ight and electron micro­
scopic findings in one patient demonstrated evidence
that these drusen are caused by thickening of the base­
ment membrane of the RPt (see Kigure 3.29] and
Dr. Cass has seen one member of a family with North
Carolina dystrophy who had a small zone of radial drusen
{see ne/a section). Et is of interest that only one of the half­
dozen patients with prominent radial basal laminar dru­
sen examined in Miami had a family history of macular
degeneration (figure 5.25D
, V
5 .1 1 M a ta ttla Eeva nt in ese - va ridbl e p h e n u t y p e .

А and i‘ : Kighl and lefl eye of a patient v.i rh ma Ini Li a leva rTt|-
nese showing symmetric арр&агап^Ё of lesions compirised of
nodular druHfn, pigmenl с lumping, and Ihe radial arrange­
ment of Lhe dTusen I и л |i o i a 11y.
C -L: Two affected sisIeijs iim(tnjj tour Hi blinds wil h fextreme
variable phenoLype. Tbe 64-ytfar-okl younger s - i buc.imo
symplomaLic around age 4t> with a vis ил I a m ity of 2tl',2L)0
Ёп each eye. Cenlral macular alrophy surrounded by nodu­
lar culicular drusen Ihdl extend nasal lo Ihe disc with radial
temporal distribution seen in hath eyes ft! and L>). lb e nodu­
lar drusen ant1 highly aulofluonescont and 1hr*-central alrophic
area is fiypoaiitafluqnescenK^ and \ . ipeclralis O C t dem on­
strates nodulai and confluent RE’L accum ulations corre­
sponding Id Iho drusen in bolh eyes IС to J). Her й b-year-old
sister had a visual acuity of 2CK-'40 in each eye and showed a
much m ilder phenolypfi (K and L'iv comprising o f small dru-
sen. arranged in a radial pa Horn in the luft eye, resembling
cuLicular d Risen of \ o rlh C arolina m acular dystrophy isee
t igure 5 .2 7 A and Й). ThciT m ii& niaJ uncle carried a diag­
nosis of L?ayne F5 honeycom b dyslrophy; lhe if moLher whs
relatively asymptomatic Ljv histon1 1 II she dic'd al age ЙО. Л
daughter and son of Lho Lwo sisters examined al age 32 and
34 w ere lA a fleeted.
N O R T H C A R O L IN A M A C U L A R
D YSTRO PH Y A N D O TH ER
H ER ED IT A R Y M A C U L A R
S T A P H Y L O M A T A (C O L O B O M A T A )
North Carolina macular dystrophy1 is an autosomal-
dominantly inheriled disorder with complete penetrance. Its
onset is in infancy and perhaps рюЩаЛу, its course is gener­
ally stable, and Us phenotype is highly variable and includes
drusen! ike changes. disciform lesions with choroidal neovas­
cularization, macular slaphylomala, and peripheral drusen.
liJeclrort’lmography, electro-oculography and color vision
are normal. lefieret aL3i3 and Jrank et л ]:"1" reported a large
pedigree from western North Carolina consisting of 545 fam­
ily membeis in seven generations wilh a dominanlly inher­
ited macular dystrophy lhat they characterized as progressive.,
usually commencing in infancy and reaching its maximum
severity in the early teenage years. Scattered lesions that they
believed were dmsen and pigmentary changes. in Lhe mac­
ula with normal visual acuity were Lhe earliest fundoscopic
changes {stage 1) fhigures 5.27A and В, 5.2SB, h-L). As Lhe
vision declined to lhe 20/50 range, there Was an increase
in the number as welt as Lhe confluence of the drusen]ike
changes (stage 2]. In many patients the fundus changes did
not progress beyond the drusen stage and visual acuity may
have remained normal. Other family members showed a
progressive decrease in the acuity lo the 20/200 level cott-
comitanL with the development in some cases of almost
total atrophy of lhe choroid, EIRE:, and retina in the LnacLilar
area (stage 3). Although J.efiefs and Frank's photographs
appeared to show evidence of stapbylomatous ouLpouching
in association wilh these severe changes- they did nol men­
tion that change. Neither did ibey describe peripheral dmsen-
like changes or evidence of choroidal neovascularization and
disci form detachment, although one of the patients depicted
in their report as well as one of our palients showed evidence
of this complication."'' Ihe retinal vessels, peripheral fields.,
color vision, ERG, and EOG were normal.'lhe general medi­
cal examination was typically nonnal except for a Lransporl
type of aminoaciduria Lhat segregated independently of
the foveal dystrophy, but tvhich was also dominantly inher­
ited. Small el al/4'' studied 15 of She original Ijefler's. and
trank's patients over !0 years and noled slahle vision and
fundus appearance in all but one eye of one palient.- thus
confirming the relatively nonprogressive nature of the condi­
tion.. Additionally, (hey noted peripheral yellow drusen!ike
changes in some of them.
Cass has seen members of ihree families from west­
ern North Carolina who demonstrated all of lhe clinical
features reported by t.eller and associates and Erank and
associates (Figure 5.27). ’Lhe yellow spots in the macula
appeared biomicroscopically lo be caused by focnil areas
of depigmentalion of the RPE in the absence of nodu­
lar elevation, as observed in more typical drusen (ligure
5.27А. В, E and l.J. In one patient there was a radial pat­
tern of drusen in the paracentral region (ligure 5.27A). All
of the drusen as well as the central spots showed prompt
j.2 7 North Carolina macular dystrophy.
A—С : Note? Lhe? d u ster of peculiar, ycllowish-whilu lesions til
lhe level of Lhe rulinal pigmenL epithelium ■ :hi PE i in Lhe matu-
lar region of tioLh eyes (A and Б) of i his lfl-year-o-ld W ornali
who had гю ibcular symptBfns and had 2 0/2 0 visual acuiLy.
A n£| ior^iii pliy revealed a pattern of hyperfluoreiicence I hat
wan apparent in lhe arterial phase [Q and did not change
in pattern during lhe course of artfciogjaphfe !\'oie lhe faintly
visible radial pattern of lhe lesions in Lhe temporal m acular
area. The central conlluenL агсан o f depigmenlation of Lhe
EtF’l may or fray nol be caused by drusenlik-e deposits. The
radial distribution ol the lesions temporally suggests LhaL they
may Eie Eiasa laminar d rjsen.
D and E: The mother of Ihe palienl illustrated in A—С had
subnormal vision all her life. The vision had not changed
for at leasl 2!) years. Her visual acuity in the righl eye was
20-40, and Lhe lufl eye was 20/200. N’cHe Lhe irregular white
Hubretinal near in addition Lo several drusen in lhe rii^hI
macula ID ) and aLrcjphy ot lhe R P t wiLh chimp ing o f Lhe pig­
ment in lhe lull m acula LE. . EioLh the moLher and daughler
had m any small drusenlike deposils in the periphery o f both
eyes. JJolh pallenls w ere from wesLern Norlh Carolina.
FiTtiis asymptomatic 7-year-old girl from North Carolina had
normal visual acuily. She had drusenlike changes similar to
LhaL in A and В bilalerally.
G - l: Excavated atroph -. ( п;ч ч :i r .11 k-ions in a 57-year-
□ld W4)man w hose vision was apparently subnormal all her
life. She had noled mild p ro fessio n of her visual symptoms
in lecenl year?. There was an overhanging lip oE retina Lhal
pari Iу surrounded ihese lesions. Visual acuily in the right
eye was 20/50 and in lhe left eye was 20/70. Angiography
revealed Lhe presence o f only a few small choroidal blood
vessels in Ihe area of Lhe m acular lesions fL).
I and K: The Ь2-year-oltf sister of Ihe patient illustrated in С
and H. NoLe lhe lip of relinal 1issue lairows, |- overhanging
the large staphylomalous Lesions. Her visual acuity in Lhe
rigfi I ey e was 2tYS0 and in I he left eye was 20/ 100.
L: The 20-year-old grandson ol the palienl illusLrated in С
and H. N'ole Lhe mull i pie drusen in I lie m acula. His visual
acuity was 20/15. Sim ilar iesions were found in lhis patient b
fa I her. A ll o f ihese pa Lien Ls had muHlple drusen in the
periphery of (he Tundus. The family was originally from west­
ern N o nh Carolina.
fluorescence (I’igure 5.27CJ. In one family ihe mother
shoved evidence of disciform macular scarring in one eye
[figure 5.27D). In lhe olher family the grandmother and
her sister showed large, deep, circumscribed, staphyloma-
tous or colobomatous areas of marked atrophy of the cho­
roid and retina, absence of high m yo p ia , and remarkably
good visual acuity (ligure 5.27G, 11, J, and K ).-” 9The son
and lhe grandchildren showed varying degrees of drusen­
like changes in lhe macula. Unlike the cases reported by
the previous authors, some of our patients have shown
drusen in the peripheral fundus. rltie radial pattern
[E'igures 5.03b and \ and 5.2SC and 1!) has also been seen
in Small's group of patietits.-' Patienls with drusen are
largely asymptomatic unless they develop choroidal neo­
vascularization. Often the parents are completely asymp-
tomalic and have been incidentally discovered when lhe
child developed symptoms (ligure 5.2b).
 The North tLarolina Macular dystrophy gene (Л4СВДШ
is mapped lo lhe 6ql4-qS6.2 region, though the dis­
ease causing gene Is yet to be identified, '[hough initially
described in inhabitants of North Carolina With their
descendancy traced Lo three Irish brothers, Lite pheno­
type has been found in Caucasian patients outside North
Carolina and the LISAr"111"2^ in African American (Figure
5.25}, Belize/'1'1 and Korean patients.2-1s A black family in
Chicago where three generations are affected is described
in Kigure 5.29.
The presumabEy congenital staphylomalous macular
tenons [referred lo by some as macular colobomas, more
recently as macular caldera by Goldberg el simi­
lar to tliat illustrated in this large pedigree, may occur in
families Lhal may show other features including Leber's
congeniLal blindness.-''"'”" progressive cone-rod dys­
trophy and skeletal abnorma I ities. ■'sa,J " Pedigrees
wilh fundus findings similar to North Carolina dystro­
phy include those of Leveille and associates"''" in a black
family, Eel ken hour and associates.1'" and Miller and
ilre s nick.21,0 SmalE and associates^ have recent!v estab­
lished that the cases reported from North £!jrolinaJ, , " ' :i
and Lhose b y iiermsen and fudisch and LeLkenhour and
associates' '' are descendants of three Irish brothers who
seLLled in Lhe North Carolina mountains Ln Lhe IS30s.
Cass has seen a 3a-year-old mother and her ] 6-year-old
son, both with moderate Eoss of central vision and large
macular staphylomata unassociated With high myopia
[E'igure П.30Л-1-]. LRG, LOG, and color vision testing were
normal in the mother. L'he son had a markedly abnor­
mal rod LFtC. ibey had no known relatives from North
Carolina. Salorre and colleagues reported a Spanish fam­
ily wilh autosomal-dominHinl biiaLera! macular colobo-
mala.jl ' Cass has seen one patient with cone dystrophy
and congenital macular staphyloma (see E'igure 5.32Land
h). ""1 Пескеnlively el al. reported macular colobomas in
families with J-ebcr's congenital amaurosis and progressive
cone-rod dyslrophy."'|:' L>r. Cass has seen another young
woman who, over a period of 13 years, developed progres­
sive macular degeneration Lhal was accompanied by the
developmecU of a large macular staphyloma in one eye
[E'igure 5.30C-J). 13er family history was negative.
North Carolina-Like Dominant Macular
Dystrophy
Ibree other families with autosomal-dominant drusen
and early-onset macular dystrophy resembling North
Carolina macular dyslrophy have been described recently
wilh loci different from 6q]4-ql6.2. One is a four-
generation British family localised to chromosome 5,
region pi3.T-pl5.33, ^GDJS^T65; second, an Lnglish
family with associated progressive sensorineural deafness
Lo chromosome 14qi,:1'; and the third, a Norlb American
family mapped Lo 6ql4 belween loci for cone-rod
North Carolina macular dyslrophy (N C M D ):
stability o l lesions.
A -F: Til i-s I й-уелг-oid fun^le nolud central тИапЪогрвйэрна
and disLorLion in- her rs^ht eye far 2 months w hich глrlu^il Jy
improved aver the nextm onlh. Her vrsion was 2Q/25- on Lhe
ri^hl and 20/20 on the left. A hypeipijim enled faiued t:enlral
lesion surrounded by a rimy c f mottled rcJiплI pigment epi-
ihelium w ilh л few p und ale drusen within il was, seen
on the rijjhl (A}. Sm all and intermediate punctate drusen disL
Lribuled within lhe* iovea w-ns seen on Lhe lefl \№j. findings
huj^csl л sponlaneously repressed lyfie 2 choroids] nn>ovaii-
LuEar membrane in a palienl w ith N C M D . Autofluorescence
и п л^ п у s le w e d л : i r>fj, of mcreased auLofluor&scence sur­
rounded by a rin^ of decreased aulofiuoiosconce corre­
sponding Lo Ihe ring of mol Iled U P t (C). O ptical coherence
Lomo^raphy itXH'.l showed no aclivity on the ri^lit. and lbe
drusen could not be picked up by O C T :LJ1 and [32:. Her
40-yt-jar-old asvmpttjmalic jnotheij with a conrfuled visual
acuily of 2tV20r shuwed hi mil a г ъгплН com pact dru-sen w ithin
Lhe Eovcm in l>oth eyes it and
’■■-L: A 13-year-old female was found to have tom pacl
sninEI drusen w ilh Lrmipoial radial arrangement in both eyes
typical of NCM fij; tin л routine examinalion for ^ksses It i
and Hi. Hour уелги laler Ihe lesions are unchanged, dem­
onstrating slaEjilily and very slow pn^ression il and I .
AulofluorescenLe was nonspecific w ilh some lesions show ­
ing puncM te hypoaulofluorescence shown. Her 4 5-year-old
fa I her was asymptomatic anti had ипплН CDmpatl drusen in
the fovea (K and L); л brother whs known to have simitar
ch-an^os w hen ^ л т 1 г « р eke w b ^ n 1.
It j - I. A ls u , Y .b n n u ^ v i. L . L w r L 'n L t ; I . , H i t l i L t m . i l A,1 i . i A ^ . L u n t b i r a ^ Ш О . . 4 7 f l -
L i- 7 t i2 t ) - i3 2 U - 9 r |3 .7 4 .j
dystrophy 7 (COftD7) and North Carolina macular dystro­
phy {М С П Щ ).257
ChoriorettnдI Coloboma
Patients with typical inferolemporat chorioretinal coEobo-
mas tbaL extend into the macula cnay occasionally develop
loss of central vision because of choroidal neovasculariza­
tion developing at the margin of the coloboma [E-'igure
3.31 К and l )- 011—'■J
Parametric linkage ana lysis originally localized the SJrO
gene lo chromosome 22ql3-qter.JJ's Subsequently, five
different missense mutations and a splice sile mutation
have beeit identified in TTAdPJ [tissue Inhibitor of metal-
loproteinases 3у * ™ [q ihe UK, all SFD faniities carr\r
lhe saine SerllilC ys TttviP3 mutation and it has been sug-
gesled that all cases relale lo one single ancestor. TIMP3
encodes an lti>L-expressed member of a group of zinc-
binding endopeptidases involved in relinaE extracellular
matrix remodeling. Mosl recently a susceptibility locus
near TJA№9 has been found to be associated with age-
relaled macular degeneration, suggesting overlap of some
disease mechanisms between the two condilions.J "''
" B E N IG N " C O N C E N T R IC A N N U L A R
M A C U LA R D YSTRO PH Y
in 1974 ОеиТгплп described benign, concentric, annular
macular dystrophy in рл tlenlu whri develop а paracentral
ring scotoma associated with a bull's-eye pattern of peri-
foveal atrophy of the Ш 5Е: and variable degrees of hyper­
pigmentation of the central macular region.' slight
narrowing of lhe retinal \ressels may be present. 'Ilie optic
discs are normal, ihe visual, acuity is either normal or
near normal, ih e URG may be normal or slightly abnor­
mal. Che LOG may be subnormal, '['here may be a mild
to moderate color vision defect, ihe disease is inher­
ited as an autosomal -Jo minanl trait Although initially
termed "benign,” a recent Ш-уеаг follow-up of the pedi­
gree described by Deutman revealed evidence of progres­
sion of benign, concentric, annular macular dystrophv
into a more genera I ized Lapelorelinal dystrophy involving
both rod and cone Function/4" A progressive decrease in
visual acuity, nyctalopia, and dyschromalopsia were found
in some members of the pedigree as well as an increase
in the pigmentary macutopalhy and peripheral bone cor­
puscular changes. Llectrophysiology confirmed equal
involvement of the rod and cone systems. This progres­
sion of the phenotype is indicative of retinitis pigmentosa
wilh bull's-eye appearance, since rod dysfunction and nyc­
talopia may be seen early. Photophobia and early loss of
central vision, features of cone-rod degeneration, are not
typical findings.ж Eienign concentric annular macular
dystrophy maps to 6p ] 2.3-q 16 in the vicinity of the inter­
photoreceptor matrix proteoglycan] (iA4PG]] gene.',l1' The
disease is autosomal-dominantly inherited. Miyake el al.
described a bu!l.rs-eye maculopalhy and a negative EiRG
(b-wave smaller than a-wave) in four unrelated males with
initially normal vision, progressive decrease in visual acu­
ity, preserved cone L-.RG, and mild to moderate deficiency
in color vision. '"1 They believed that ihese palients had a
disease similar to benign concentric annular dystrophy,
although none of their patients had evidence of domi­
nant inheritance. LOG is almost always subnorm aE or
abnormal and deteriorates wilh age. Dark adaptation also
decreases with Lime. Visual fields may be normal early on
and show a rtnglike /one of decreased sensitivity around
a sma!I central island. Blue-yellow color vision may be
deficient.
The differential diagnosis of concenlricr annular, macu­
lar dystrophy includes cone dystrophy, rod cone dystro-
pEiy lipofuscinosis, chlonocjuine retinopathy bull's-eye
maculopalhy associated wilh Stargardtrs disease {fundus
tlavimaculalus). sporadic progressive loss of visual acuity
secondary to bull's-eye macular atrophy without cone dys-
Lrophy fenestrated sheen macular dystrophy, parafoveal
atrophy of the RPL secondary to drusen, and aulosotnal-
dominant central areolar chorioretinaE dystrophy unasso­
ciated with flecks (I'igure 5.12G-]).
j. 2'J North Carolina macular dystrophy in an African
American family^
A-D: Ibis Л1гкдп А т е Ь с а п m.ile hnd 2W25 vision in EksIIi eyes
rind belonj’ud to a family exanHrtfid over four ^нпепИio?is w ilh
jp H o m a lly inhoriLed jfriacula^ dystrophy in Chicago. H ll had
confluent ^nd noncortfluent drifts ri confined !a I he? love л ir>
both eyes {A and Bf. Thu lesions show window defects on angi-
oi^aphy iTJ Lind Hi у molhtfj and maternal grandfather WS№
miamined in 1(J7Q wiLh bibitemi macular lehionn and were then
^iven a dia^ntttis of cenlTal JTeolar choroidal alroptiy.
E -H : The son of the above patient had bilateral staphyloma-
Lous lesions IE and I" with cufiI m I aJrophy shoWLJig loss of
choriocapillaris on the an^iqjifam .CJ and 1-1), SLErroLrnded by
sи brut iпа I fibrosis.
I and |: An older maternal cousin was txiinim ed in N e w
York who also bad a similar staphylomatous lesion ll) with a
visual acuity of 2(t/b0 that showed Ures ol auU'fluorescence
with a rin ^ o f hyporaulofluoreHcenfje al Lhe ed^c of Liie lesion
11). Several other member* of Lhis lam iJy have been ш т -
ined at various Limes [jelwoen 1У79 and .200У and found lo
have eilher Lhe drusen or lhe sLaphylomatuus phenotype. The
iiiheritiinte has been in ;in aulcHomal-dwliinant pnllern.
f. jju r U tnf Ur. L ijn ic K iLTiun . LJr. Sc спи M.sn p hie a d an d Ь т. W illia m
К J . l M '. ' H i I м ,1 A l l , i s .
M i t ' J t / r . 1. a n d ]■, A l i r > , V ^ n c i u j ' j i i . l . - . i m c r n . L '
^lunyb’r. JttlCi, ^7iU).7(i2Ci-ijICi-4r [П.7.Ч.
JU V E N IL E H E R ED IT A R Y D IS C IF O R M
M A C U L A R D E G E N E R A T IO N
Disciform macular detachment occurs infrequently in
children. When it occurs unilaterally in the absence of
abnormalities in the opposite eye, it is usually attributed
lo an inflammatory lesion such as Toxocctm cjnis, diffuse
unilateral subacule neuroretinilis, and toxoplasmosis,
or to a posttraumalic choroidal rapture. Occasionally, a
child with rubella retinopathy [see I'igure 7.27), pars pla-
nitis (see Hgure 7.75}, acid multifocal choroiditis and
panuveitis [the pseudo-presumed ocular histoplasmosis
syndrome} may develop a disciform macular detachment.
Some patients with best's vitelliform macular dystrophy
may develop choroidal neovascularization and Lhe various
slages of serous and hemorrhagic disciform detachment
{see figures 5.ф ь and 5.03GJ. Choroidal neovasculariza­
tion has occurred in two sibling children with juKtafoveo-
lar retinal telangiectasis. ' 1 En general, however, disciform
macular detachment in children secondary lo hereditary
disease apparently occurs rarely. Al the 1979 .International
Fluorescein Angiographic Meeting at Hath. L>rs. Alan bird
and Steven Ryan briefly presented two families with mul­
tiple children wilh bilateral disciform macular lesions of
unclassified type, in Miami we have observed bilateral dis­
ciform detachment of" unknown causes in several childreLi
wilhout a family history of macular degeneration, and in
two sisters. Ihe findings by Hi i d and Ryan suggest Lhat the
clinician should be cautious in making a diagnosis of bilat­
eral disciform detachment secondary to an inflammatory
cause withouL carefully examining other family members.
э.3'.I Familkil bilateral macular staphylomata.

A -F: Ttiis 28-year-old mother LA-Q and her 16-year-old boy

ID —h) had minimal eye complaints. She noled (rouble w ilh
her near vision for -f ye a n . I-Ier visual acuity w a-ь 20/200
in 1hch righl e y e and 2(У50 In lhe* lefl c-ye. Hin visual acu ­
ity was 20/200 and J-I in lhe li^ht eye and 2 ^ 1 0 0 and |-1
in Ihe lefL eye. Bolh had normal color vision and electro-
Dculujjraph-k: Tin[lings. The mother'!- electraetijtaftfern was
normal. The son had markedly subnormal rod responses. The
cone responses wttre normai Гhere was no oLber family his-
Lory of eye disease. The family was from Indiana and had no
known relatives in Korth Carolina.

NonfamiliaJ progressive macular dystrophy and

unilateral macular staphyloma^
G —|: ThFS 43-year-old wom an f^ave a 13-year history of
decreased vision in Lhe rijjhl eye and a rucenL hds-1ory of
Visual change m Ihc.=- [fin eye. Com pare fundus moLts- made
in 1975 iG and H>, wiLh chase made in 1 ЭВ7 fl and j). Note
in the righl eye Lh*f change frcim geographic atrophy of reLi-
naf bi^rrierft cpilhuliunn i<_ii Ln a lar^e si aptiy Jcma (arrows, I .
and 1ht! development of mu ItipJe areas of врофГарНй: atrophy
in Lhe left eye 11■. Her visual acuiLy № 20/400 ri^hl Eye and
20/25 left Efye Hi lhe Iasi eatatjaination. Her family histtny was
negative. She missed mosl ol Lhe H R R color pi a les with each
eye, N o elecLropiiysiolo^ic information wan obtained.

Chorioretinal coloboma associated with choroidal

neovasc ula rizat iол .
К and L: Eh i-s J 5-yea г-old man developed metamorphopsja
caused by a io taH ^ 'd serous detachment that Was associ­
ated with a local area m sLainin^ |arrow, Ll aL Lhe superior
lim ol Lhe*- staplwloma I a n o w s. Kj. Thu m acular delach-
ment resolved after laser pbolocoagulation LjuL subse­
q u e n t recurred along w ilh lurlher evidence of choroidal
net)vascu lari nation.
P S E U D O IN F L A M M A T O RY
S O R S B Y 'S F U N D U S D Y S T R O P H Y
(SF D )___________________________________
In 11>4У iorstjy and associates'" 1 described five families
with dominantly inherited macular dystrophy that ujas
characterized by the development, usually during the fifth
decade of lifer of choroidal neovascuEarization, sub retinal
hemorrhage, and changes suggestive of disciform degener­
ation (Figujfe 5,31 Л-E-'). Progressive atrophy of the periph­
eral choroid and fcPE occurs later in life and in some cases
causes loss of ambulatory vision. LJnfortunately Lhe loss
of peripheral function has generally been overlooked.,
as indicated by the name pseudo inflammatory macuiar
dystrophy, '['his name was chosen because Lhe extensive
macular and paramacular changes have suggested to some
a past inflammatory change. The term "pseud иinflamma­
tory* is perhaps unfortunate for other reasons: [ ] ] many
of the patients have a disciform scar that is indistinguish­
able from that seen in a host of diseases, including senile
macular degeneration and angioid streaks; ( 2) the fact
that the scar extends away from the macula is a nonspe­
cific change that may occur in patients with senile macular
degene ration and angioid streaks; and (3) some patients
with typical dominantly inherited macular drusen may
develop disciform detachment in the fourth decade or ear-
Eier. Ashton and Sorsby"' ' studied the eyes of two sisters
with this condition and noted histopathologic changes
similar to those of senile macular degeneration and angj-
oEd streaks in patients with pseudoxanthoma elasticum. AL
least three of the original families reported by iorsby and
associates showed some evidence of drusen deposits at the
level of Bruch's membrane. One of his fainiLies (kempsler
pedigree) had peripheral retinal dysfunction [progressive
loss of Bight vision for up to 25 years before loss of central
vision)., a deposit of yellow subrelinal material throughout
the fundus, a tritan color defect, and loss of vision occur­
ring because of choroidal neovascularization by the fifth
decade of life. Some patients lost central vision because
of geographic atrophy/'1' lhe yellow material tended to
become less apparent with age. Light and eEectron micro­
scopic examination of the eyes of a 65-year-old descen­
dant of the Kempster family demonstrated a thick deposit
within llruch's membrane that stained positive for lipids.,
gross loss of the outer retina and KPE, and atrophy of the
ehoriocapilJaris.' Although no yellow change in the fun­
dus was apparent iust prior to death the thickened layer of
material between lhe basement membrane of the RHL and
the inner collagenous zone of Bruch's membrane may be
Lbe honiologof the yellow material seen clinically earlier
in Eife. These changes were not noted in the histopatho­
logic study of the eyes of one of two sisters described by
Ashton and Sorstjy.''*
Dreyer and Midayal described the clinical and histo­
pathologic findings in a f.tmily with dominantly inherited
Ь. .■!E So rsby 4 tun du s dyst rop hy^
A-G: A 55-vear-oEd wom an was diapfiusied with m acular
degeneration 10 years previously w hen she received laser to
bleeding ir> her righL eye. Her mother and maternal gjand-
moLher weft; diagnosed with m acular degeneration in Lheir
30 ы und 60s. Her visual acuilv 50 in edchj eye. In
addition It) pari Iу atm phic and pnrtly fibrcitic scars in bulb
macuLi* I hi' patient hajJ mu'Upkv'lar^e JihcrtOidal neotLiscu-
bir membranes with suEjreCinal blood and fiuid. There were
estens-ive pseudodrusenlike L'hant^s extending up [a, and
^interior lo, lhe et|Uii[(jr in Eioth eyes iA -U i. FRjOt&sciem
angiogram shew ed earlv hyperffuurescente <?l" lhe dru­
sen and leakage curruspendiny te lhe choroidal neotascu-
lar memFjranes ■El and Fj. Her СоЫплапл visual Fields were
moderately constricted. C iven lhe early age of" ел set and
sUung family hislory she underwenl genelic lestinjj and was
positive For H M F 3 mutation. 5he received inlravilreal anli-
vancular endothelial growth Pador a n l i E w d i e s .
early-onset peripheral and central visual loss with marked
EOC change&J ■ ’M ’he histopathologic changes were similar
lo (hose seen by Capon et al.r- ' except no thick sub-IU’ H
deposit was described. El os kin el al. noled a confluent yel­
low deposit confined to the macula and angioid streaks
in another of Sorsby's pedigrees ( hwbank}.-'' lhe yellow
material in both families was associated with some del<iy
in the appearance of fluorescence angiographically that
was interpreted as evidence of delayed choriocapillary
perfusion.
it is of interest that in a follow-up report of the origi­
nal five families of Sorsby and associatesr two palients
were found with a typical fundoscoplc picture of angi-
oid streaks and multiple fine drusen Iike deposits that
appear identical to the peau d'orange change occurring
in patients with pseudoxanthoma elasticum/ ': Ehere was
no mention in the report as to the presence or absence of
lhe skin lesion, ^orsius and associates^* have reported a
l:innish pedigree with a recessively inherited pseudoiin­
flammatory dyslrophy characterized by colloid bodies
deep within the retina that they tikened to those occur­
ring in relinitis punctata albescens (tilVv), angioid streaks,
and widespread areas of choroidaE atrophy and pigment
derangement as the disease progressed. A four-generation
pedigree characterized by submacuEar neovascularization
in the third to fourth decade, yellow punctate deposits al
the level of the pigment epithelium, myopia, nyctalopia
beginning in childhood, mid peripheral equatorial pig­
ment clumping and migration, and electro physio logic
abnormalities was reported from Oklahoma.-'14 Hamilton
et al reported a seven-generation pedigree with loss of
central vision between the second and fourth decades.
While to yellow fundus spots, atypicaE for drusen. accom­
panied a disciform degeneration in many patients.-*'
boone had atrophic maculopalhy and others showed no
spots. Atrophy of retina and К E^L spread to lhe periphery.
Wu et al. studied two brothers of ramify wilti dominant
L
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: : г * '-.ipc d l l i т е I ь г р *г г с с ч п : n г ■ч ч i hhdc .:г ? : г r S i
' 4"
■ *i'i ipvH«pA!сзРп*7 "S*v-P-sl>I ! NOI\i йг-f»1нГу>р|
inherftance, They described generalized ftn-e RPE gran­
ularity, iris ^osiEliu^natlD fl defects, LRG changes, dis­
ci form Lesions, iind angiographic evidence of delay in
choroidal perfusion in Lwo brothers aged 28 and 34 years,
fedyeat and colleagues described a dominantly inherited
pedigree characterized by onset o f nyctalopia beginning
in childhood, myopia, subretinal neovascular membranes
and yellow punctate deposits at the level of the RPli, mid
peripheral and equatorial pigmenL dumping and migra­
tio n and ERG abnormalities/*1 Sleinmetz el al. studied a
family with poor night vision and diffuse yellow deposit
at the level of Bruch's membrane in the posterior pole._M
Ihere was minimal change in dark adaptation in the
region of ophthalmoscopically normal fundus.
The term ''pseudoinflammalory fundus dystrophy"
should probably be confined Lo dominantly inherited
pedigrees, who in the fourth and fifth decades of life
or earlier lose peripheral as well as central visual func­
tion associated u'ith serous and hemorrhagic disci form
detachment una&sociated with macular drusen (E-igure
Ъ.1\Л-¥).27*'2 т ™ - 1й7
H E L IC O ID P E R IP A P IL L A R Y
C H O R IO R E T IN A L D Y S T R O P H Y
(" C H O R O ID IT IS AREATA/'
S V E IN S S O N 'S C H O R IO R E T IN A L
A T R O P H Y )_____________________________
This is a rare, distinct bilateral autosomal-dominant fun­
dus disorder characterized by sharply demarcated, wing-
or prupellerlike atrophic chorioretinal lesions radiating
away from the optic discr in the absence of evidence of
inflammation [serpiginous choroiditis), angioid streaks*
myopic degeneration, and paravenous retinochoroidal
atrophy.J D 3 Mild astigmatism is common,JQJrJG7 It was
first described in fee land in 1939 by Sveinsson who
named it "choroiditis areata"; Franceschelti in 1962,M|
renamed it helicoid peripapillary chorioretinal degen­
eration due lo the lack of inflammation, and Sveinsson
redescribed four affected successive generations in 197У
demonstrating dominant inheritance and progression with
fji.ни- lesions can be seen at birth and progress
slowly with late macular involvement, lhe topography of
the lesions suggests that they may result From tearing of
liruch's membrane and ftPE.m:| All cases so far have been
described from Iceland, and the ones seen in Canada,
Denmark, Faroes, Germany, Norway, Sweden, Switzerland,
the UK. and the 1(5A all have ancestors in Iceland who
are members of the extended Icelandic pedigree. En
order to prevent ambiguity associated wifll the term heli­
coid peripapillary chorioretinal dystrophy, the name
SVetrusou's chorioretinal atrophy has been proposed.Щ
lhe defect has been mapped lo the 11 p lS region by link­
age analysis.-1* 4' ,0!l
э.ЗЕ Continued
Cone dystrophy.
H -K : Tbrs 10-уеаг-old boy failed vision screening a l his
school. W ith н mild refractive corrrcjtian tii-s vision tfilprtiw n
La 20/50 on Lhe rif^bL and 20/50- on Lhe le ft There was лп
oval bulls's-eye-Lype d i-алоде in both m acula. The fundus
Lotor was normal wiLh visible choroid-al vessels clin ica lly
ruling (h j L Slargardt's disease. A central fovea I increased
auLofluorescente surrounded by a risng of decreased aulo-
fluonescente correspond? la Lhe bull's-eye Lhange Lypiral of
Lone dysLnophy.
l A —C r , c u U l f & y erf Lj r . L c tu b 'in S l u m . ' : H - K . ■ n j L i r l i i s y o l D h . H r Л и т I £ s [ t f t :,j
C O N E D Y S T R O P H Y (C O N E
D Y S G E N E S IS )
Cone dysfunction may occur as a result of eilher a mal-
development of the cone system that is associated eilher
wilh no or minima! progressive deterioration of lhe ret­
ina (nonprogressive cone dysgenesis], or with enity malic
defects that lead to progressive deterioration of the cone
system (cone dystrophy).
Nonprogressive Cone Dysgenesis
C ongenital Achrom atopsia
Congenita] achromatopsia is relatively rare and palients
present with poor Vision from birth, nystagmus, vary­
ing degrees of color vision loss, and photophobia. Ihe
conditioii is usually nonprogressive. ihe nyslagmus may
improve and become Less prominent over time, lhe fun­
dus examination is usually nortnal but occasionally
peripheral pigmenL alteration or bull's-eye marulopalhy
will be seen. Most patienls are hypermetropic. !iRG shows
normal rod function but no cone function.
Complete Achromatopsia (Typical Achromatopsia or
Rod Monochromatism)
Complete achromatopsia has an incidence of about 3 in
30000. ll is a recessivelv inherited disorder characterized
by either complete absence of or severely limited color
vision, reduced visual acuity, nyslagmus, and photophobia.
The visual acuity is usually in the 20/200 or worse range
wilh debilitating aversion to light. Full-field cone ERG
responses are eilher absent or severely reduced. The fundi
may show absence of the fovea I reflex and mild distur­
bances of the pigmentation in the macula.. Histopathologic
exam illation of eyes with complete mo noch nomat ism has
shown S-10% reduction in the normal number of esLrafo-
veal cones and abnormal structure of the foveal cones.-!|: 111
They have normal rods. These palients show no perception
of color and all colors can be matched to various shades
of gray. The Sloan achromatopsia test allows these patienls
to make matches of various colors to shades of gray lhal
Сone D ystruphy (Сдпс D ip ig trU sii) 307
is not possible in patients with floimal vision or a more
benign congenital coEor vision deficiency. Jhree genes have
been implicated so far. About one-quarter of the patients
are associated with C N G A 3 mutation, about 45-50% with
CNCЦЗ mutation, and ihe third gene responsible, CNAT2,
is found in less than 2% of palients.,|J
Incom plete Achrom atopsia {A typical
Achrom atopsia)
ihese patients have a mild ability Lo discern color though
abnormal, and have somewhat heller visual acuity as com­
pared to the complete achromats. lhe condition is also
inherited as an autosomal-recessive inheritance Where
mid- and long-wavefenglh cones are probably present
to a small extent. Mutations in CNG'Ajj have been found
til patienls with incomplete achromatopsia, the pho­
tophobia is more severe than the Eoss of vision. 4'bese
palients often wear more than one pair of sunglasses due
to extreme photophobia, lied contact lenses help alleviate
some of (he photophobia.
C o n e jV/on о ch ю т а tism
'JVvo of lhe three cone systems (b small, M medium, and
t long) are absent or nearly absent in these palients. '['he
more common forms of cone monochromatism are those
thal have either lhe red or the green cones, as compared to
blue monochromats.
X-Linked Blue Cone Monochromatism
Palients with X-Linked blue cone monochromatism are
males having subnormal visual acuity, pendular nystag­
mus, photophobia, myopia, minimal I'un Ju s changes, and
psychophysical and eleclrophysiologic evidence of both
normal rod and blue cone functions. Neither red cone
nor green cone function can be demonstrated psycho-
phvsieally. Mutations in the L- and M-opsin gene array (hat
resull in the lack of functional L- and M -pigments, and
thus inactivate the corresponding cones, have been Iden-
Li.fied in lhe majority of cases with blue cone monochro­
matism.'■' ''1 Provisional assignment of the gene locus for
blue cone monochromasy is in the vicinity ofX q 2 S.:::
Congenital Color Blindness
Deuteranomaly resulls when a normal middle-wavelength
[M J cone pigment is replaced by one that has a peak sen-
silivily at a longer wavelength {L). Prutanomaly results
when the normal long-wavelenglh pigment is replaced by
one lhal has a peak sensitivity at a shorter midrange wave­
length. Prolanopia is caused by tack of a red cone pigmeLil
and deuteranopia by Jack of green cone pigment. Visual
acuity and the ocular fundi are normal. They are also
inherited as an X-linked disorder and Lhe gene defect es at
Xq28. Congenital tritanopia, if it exists, is rare.Jl^
Sr32 Cone dy strop by,
A and B: This 5 1-year-old wom an com plained o f visual dis­
tortion and day blindness. Sine.1denied color vision abnorm al­
ities iind had normal responses Eo color vision- tesliny. Family
history was negative. Visual acuity was 2.0/20. Her electro­
ns inographic co n e responses were subnormal, and Ihe n(id
responses w ere noimal.
Q nind E?: С оле dystrophy in a 29-year-old man com plaining
□I loss ol vision and day blindness. Note the bulE's-eye pal-
Lem oE retinal pigment epithelium fRPE) atrophy in both eyes.
His electro-reEinogjam showed no cone responses and nor­
mal rod function. H it electro-oculogram was normal.
E and F: Cone dystrophy or dysgenesis in a 32-year-old man
who has had subnormal Visual acuily and color blindness since
childhotxJ when he was diagnosed as having a "hole in the
retina." His visual acuilv had dccneasod irom 20/Я0 lo 2№2QO
rkiriitij IEhj past 2 years, hie had bilaterally symmetric rfaphyki-
maloLK fovea I lesions. Note sli^hl narrowing ol" the retinal ves­
sels. His cone elecEFO-retinoyram was moderately abnormal.
Hie rod eleclrorelinogram and eleclEO-oculofljam were normal.
FrirnswujfLh-MjnwlJ l OO-hueEJtetingshowed a Lrilan axis.
G : The 23-year-old color-blind sister ol patient shown in E.
Jrtfere was a Eainl perilotetilar rin^ of KFfc aLrophy bilater­
ally. Results ol eleclro-relino^rapEiy, electru-ocu logjaphy, and
color vision Ieating w ere idenlical to those of her brother.
H : This 2 2 -year-old man noted day blindness al 22 years of
age and later progressive loss o( cenLraE and color vision. His
visual acuity was 2 0 ^ 0 . His fundi w ere unremarkab3e. His
eiectroretinograpliic and electno-oculogjaphic findings were
normal. His sister and mother had similar complaints.
I: M ol her of patient illustrated in H.
Cone dystrophy with Miizuo-Nakamura phenomenon
j-L: LaEe-onseE X-linked recessive cone dystrophy wilh
lapelc-like sheen and Mi^uo-,Nakamura phertplnnenort. Note
iridescent КГЕ changes i.p and Kl Lhal partly disappeared after
dark adapEaLion ILI.
11—L Inirn H-LMkiTilivuly ;ind WuHiur. ■J l(Jf5b, Arnurk in Vn.'dic.il
AslfttiaJ Hjn. ЛИ ri^hls ftntTwcl. '' ■
Goldmann-Favre Syndrome
Ihere is increasing evidence to suggest that Cold man n-
]:avre syndrome may be a genetically determined re Lin .si
receptor dysgenesis primarily affecLlng the cone syslem
in which an overabundance of S-cones parlly replaces the
other cone types, (йее p. 36Ё, ch 5.)
P R O G R E S S IV E C O N E D Y S T R O P H Y
lhe term Acone dystrophy* is used Lo describe Lhose
patients with a heritable dystrophy in which predomi­
nantly the cone syslem is affected.J ',i|- ■ u t Et includes
some patients in whom no evidence of rod dysfunction
develops as well as those in whom rod deficiency later
develops but cone deficiency predominates.417 Holh types
may be seen In lhe same pedigree. Most cases are spo­
radic. but when they are familial, most are autosoma l-
OF X-l inked cone
dystFophy. [n X-l inked cone dystrophy, pseudoprot-
anomalv nind abnormal fovea I densitometry findings
have been identified in female carrt^cjL^32 Щ other fami­
lies fundus changes and abnormalities in color vision..
BRQ and visual evoked potential were found in female
carriers S5J Lhe age of onset, severity. and rate of pro­
gression vary from family lo fjjnily and wilh in the inline
family. Ihe age of о nsel varies front childhood lo midllfe
or beyond, ihe clinical features, nil! of which or only some
of which may be present, initially include: [ 1 ] onset of
progressive visual loss; ( 2} impairment of color vision
even with minimal acuity loss; [3] impaired visual func­
tion in brightly illuminated situations and heller vision
in hytftgbt or dim illumination and day blindness I'hem-
eralopia); [4 1 normal or near-normal fundi initially and-
later, KPt atrophy in the macula often progressing to a
bull's-eye pattern: (5J temporal pallor of the optir disc in
some palients; ( 6) fluorescein angiographic evidence of
depigmentation of the RPE in the macula (often antedat­
ing visible alterations in the fundi); (7) central scoloma
wilh normal peripheral fields; and ( 8) reduced or non-
delectable photopic as well as abnormal flicker response
ERG. Some patients may demonstrate a supernormal sco-
Loplc Ейе £?Иг3 Karly selective involvement of the blue
cone system may occur in some families with autosomal-
dominanl inherilance.5 , Visual amity varies
from 20/20 early lo 20/200 or less laler. The macula may
he normal (figure 5.31] i), or it may show a variety of
changes, including mollling and clumping of the pigment
epithelium, a bull's-eye pattern of depigmcnlalion. focal
chorioretinal atrophy, and a macular staphyloma (ligure
5.321-. and ' The bultrs-eye pattern of RPE atrophy and
a corresponding zone of byperiluorescence surrounding a
central non fluorescein spot similar to lhat seen in chloro-
quine retinopathy are the most, commonly described bio-
microscopic and angiographic changes in these palients
(figures 5.31G and II, 5.32A, C( and l>). Occasionally
temporal pallor of the optic disc may be the only fundus
change. Auto fluorescence testing can show increased auto­
fluorescence in a ring around lhe fovea surrounding an
area of central hypoaulofluorescence that corresponds lo
the bull's-eye atrophy (Kigure 5.31 E and f).1"^ An acquired
fixation nystagmus may be present. A few patients with
predominantly the peripheral portion of lhe cone system
affected may have normal color vision performance in the
presence of a subnormal photopic ERG (l igure 5.32A).
Some of these patients may present wilh complaints
of progressive day blindness yet haw normal visual acu­
ity ' ' 1"' Gonversely, if the central portion of Lhe cone
system is primarily aflected, patients may have subnormal
visual acuity, abnormal color vision, and a normal photopic
tKG. As the disease progresses, they will develop abnormal
photopic 1LRG findings. Many patients evenlually develop
some el eel roreli nographic evidence of abnormal rod func­
tion. " " lhis varies in severity. When severe, it is associated
with varying degrees of optic disc pallor, narrowing of the
relinal vessels- and peripheral field loss. Often there is no
or only minimal evidence of pigment migration. The E-.OG
may be normal or abnormal. Patterns with cone dysLrophy
and fundi resembling retinllis pigmentosa rarely complain
of night blindness. Despite an extinguished К KG they may
show either .1 normal or mildly abnormal dark adaptation
curve, lhis discrepancy is seen also in chloroquine retinopa­
thy. lhe earliest histological changes seen are distortion and
kinking of the fovea! receptor segments folloxved by Loss of
nucleus and the rest of the cell bodies. Histopathologic and
ullraslmclural findings in an eye removed after develop­
ment of ERG changes of rod involvement showed changes
in lhe peripheral retina similar lo Lhat of mild retinitis pig­
mentosa. ",u lhe differential diagnosis of a bull's-eye macu-
lopalhy has been discussed elsewhere (see p. 300).
Lhe progression of cone dystrophy is usually more rapid
in patients wiLh early onset of visual symptoms. Visual loss
is usually, but not alwaysr symmetric, lhe acuity usually
does not decrease much below 20/200.
Some patienls with cone dystrophy will show, in addition
to reduced or missing potentials al Iighl-adapted conditions
and reduced photopic flicker frequencies, a supernor­
mal dark-adapted b-wave amplitude [supernormal rod
1Ж ] ) . ': ’ '' ' i:‘ Some patients showing this latter ERG find­
ing have a congenital stalionaryr cone dysgenesis, whereas
others demonstrate evidence of a progressive cone dystro­
phy. Most show pigmentary changes In the macula lhat in
seme patienls has a bull's-eye palLern. MulaLions in KCjW2
which encodes a subunit of a vollage-galed potassium chan­
nel in bolh roils and cones has been found recently1,!
An X-linked form of cone dystrophy may have a golden
sheen Lhal disappears on dark adaptation; this is known
as the Mizuo-Nakamura phenomenon (Figure 5.3 2[-[.).
Female carriers can have a wide speclrum of finding^,
some appearing relatively normal to those having bull's-
eye change in the macula. X-linked cone dystrophy has
been mapped lo three loci on the X chromosome.
Aulosomal-dominaul cone dystrophy or cone-rod dys­
trophy has been associated with several mutations that
include [nutations of the peripherin/RWS gene, the GflX
gene, the relinal gu any Iale cyclase gene (ЛЁТ-GCl), the
guanylyl cyclase-activating protein 1 (iJC A P J) gene. A ll'L l,
C.UCY21X Р1ТРЫМЗ, ГКОЛЛ, R IM S], SLMA4A, and
gene.3SJ 1,'i Heripberin RD S Is present on bolh rod
and cone segments. CKX codes for a photoreceptor-specific
domain transcription factor, lhe W£"JLG CI and CCAP1
gene are involved in cyclic gu anosine monophosphate
(cGM P] production. Different mutations within the same
gene and mutations of several genes result in variable
severity of the cone dystrophy. '1'
Late-Onset Sporadic Cone Dystrophy
Patients with late-onset sporadic cone dystrophy, who
are often older than 50 wars of age at the onset, develop
slowly progressive loss of central or paracentral vision
usually ill the absence of any fundoscopic abnormal i-
lies.,J 1■1 1 Visual acuity is often normal or near normal
at presentation. Detection of color vision dysfunction is an
important clue to early diagnosis because initially full-fietd
hRC findings may bt normal.'15-5 These patients are often
subjected to extensive neurologic investigaLions, '['he dif­
ferential diagnosis in patient?, particularly if they present
with asymmetric paracentral field defects, or with a history
of rapid onset of visual loss (hat may be associated with
photopsia, includes acute zonal occult outer retinopathy
(see Chapter It ] attd occult macular dystrophy. Drug tox­
icity has been implicated in acute cone degeneration.
A subgroup of patients with StaigardL's disease [atro­
phic maculopathy, flecks, and a dark choroid on fluores­
cein angiography J present with hemeralopia and HRG
changcs typical for a cone dystrophy. ЧЪе disorder is reces­
sively inherited in these patients with few exceptions.
lhe retina! dystrophy associated with autosonial-
dominant cerebellar ataxia may affect primarily the cone
system [spinocerebellar ataxia 7: SCA 7, see later secLion).
Two of the four patients described with Lbis association
showed, in addition to the typical E-RC findings of a cone
dystrophy a supernormal dark-adapted b-wave.'
Some patients with cone and cone-rod dystrophies
may exhibit a bright tapelo-lifce retinal reflex.3J5,-UD-355
Eleekinlively and W'eleber reported a late-onset cone dys­
trophy with X-linked recessive inheritance in patients with
a greenish-goIden iridescent RPE change in the posterior
pole (Figure is./Jlf-L).' 1" I'hese patients demonstrated
the Mizuo-Nakamura phenomenon and were prone to
development of rbegmatogenous retinal detachm e n L [see
Oguchi's disease, Kigure 5.37). In a family with domi­
nant cone dystrophy. Noble et al. observed a scintiElat­
ing golden reflex, identical to that seen in female carriers
of X-linked retinitis pigmentosa in the son and a diffuse
golden-gray sheen similar lo that of Oguchi's disease in his
mother.1" Л golden sheen and pigment disturbance may
also occur in families with progressive visual loss, nor­
mal ERG findings, and absence of the Mizuo-Nakamura
phenomenon.
Analysis of genomic DNA isolated from affected mem­
bers of a family of X-linked cone degeneration revealed
a й.З-ldlobase deletion in the red cone pigment gene.'-'1
deduced levels of alplia-l-fucosidase activity in leukocytes
was found in two patients with sporadic cone dystro­
phy.1'" Screening of 24 pa Lien Is with several forms of cone
dystrophy failed lo find this abnormality.121 Antibodies
against human retinal proteins have been identified in the
serum of some patients with cone dystrophy.33*
I Leavily tinted glasses or miotics may be helpful in alle­
viating photophobia in patients with cone dystrophy.
FEN EST R A T ED S H E E N M A C U L A R
D YSTRO PH Y
1'enestrated sheen macular dystrophy is ап autosomal-
dominant гласи]йг disorder ch a ira ^ lie d in young
patients by liny red fenestrations occurring in a centra!
macular zone of a golden sheen [E'igure 5.33A-C).1,
Multifocal areas of hypopigmentation of lhe Rft: become
manifest in the paracentral area in young adulthood, and
Lbis may progress to an annular zone of depigmenlalion
by the fourth decade. fluorescein angiography shows win­
dow defects corresponding lo the t№£ changes and not
related to the red feneslralions. lhe visual acuity may be
mildly affected in late adulthood and ranges from 2U/2L>
to 20/30. Mild changes in the К KG and HOti and color
vision abnormalities may develop. The sheen reflex that
appears lo lie between the level of lhe RPE and retinal
vessels persists, but the central fenest rat ions disappear as
more changes in the R P t occur. L>aily and .Vlets suggested
that this disorder may be related lo a defecl or abnor­
mality in macular xanLhophyII.,,,u Eh is disease should be
added to the list of bull's-eye maoilopathies.
D O M IN A N T L Y IN H E R IT E D
M U L L E R C ELL S H E E N D Y S T R O P H Y
(F A M IL IA L IN T E R N A L L IM IT IN G
M E M B R A N E R ET IN A L D Y S T R O P H Y )
Pom inanlly inherited Muller cell sheen dystrophy is a
rare, previously unreported disorder characterized bio-
microscopical ly by prominent glistening light reflections
emanating from the inner retinal surface Lbat appears to
be thickened, yet translucent, and thrown into a pattern
of railroad track-like folds (E'igure These
changes are most prominent bul are not limited lo the
posterior fundus, Ihis dominantly inherited disorder
is apparently associated with minimal visual morbidity
prior lo midlife, when patients may experience visual loss
in one or both eyes as the result of biomicroscopic and
angiographic evidence of widespread intraretinal edema
(E'igure 5.33E3-E3). In addition lo typical cystoid macular
edema, there is a pattern of superficial micnocystic changes
that extend throughout lhe posterior fundus. ViLrectomy
in three eves of two members of the same family bas
failed to improve the visual funelson (l:igure Fr.33EU—E).
One family member developed monocular loss of central
vision that was attributed to vUreomacutar traction. Pars
plana vilreclomy failed to change either the visual func­
tion or lhe appearance of the fundus [E'igure 5.331>-1 i).
i Iistopathologically these fundus changes are caused by
thickening and undulation of the internal limiting mem­
brane of lhe retina, superficial retinal schisis. and cyslic
spaces in the inner nuclear layer. All of these changes sug­
gest д primar)r defect in the Muller cells (figure 5.3JJ-1.).
5.33 Fenestrated sheen macular dystrophy^
Д—(7: А 32-year-old man with рй й и тйс) dom inanlly inher­
ited lenestraled sEwen m acular dystrophy He complained of
recent loss of vision. His acuity, which had previously been
20^20, was 2CV40. His family history was negative. His color
vision and electronelinographic findings w ere normal. The
small, dark, lencstraied areas within- lhe ^liHtoniny sheen
in the central т а с Ы л г area are barely visi 111e in lhe pholo-
[iraphs. Angiography showed mol Iled hypcrfluonnscence cen-
Lrallv huL no evid en ce of abnormal staining.
Dominantly inherited MulEer cell sheen retinaE
dystrophy ffamiltal internal limiling membrane
dystrophyh
D -H : This ii.'i-year-old т а л , his sisler, his mother, and a
maternal second cousin had a long-standing history o f a
peculiar fundus glistening reflex change that. In the palieni
and his cousin, Wiis associated w ilh some visual loss. The
patient liad laser treatment for recurrent idiopalhic tenlral
serous chorioretirKipalETV in January 1454. Hi я symptoms
failed lo ms pond to laser Imatmen'. There w ere marked glis­
tening reflexes and some distortion o f the retinal vessels in
bo-lh eyes. There was clinical and angiographic evid&mce of
macular edrm a in the rigEhL яуе {D and Ё]. This edema uqis
alLributed lo vitreom acular LracLion and a |>ars p]ana viLrec-
tomy was donE in September 1994. This resulted in m ini­
mal change in the fund-us appearance and vjsual funcLion.
In Decem ber 1У94 his visual acuity was 2CV20C- ri^hl eye
and 2(V25 left eye. He missed all of the iHNFi plates w ilh
Lhe righL eve and go! nearly ail or" i Ei e j t i i w ilh IE t f 1 lefL eye.
EJiomicroscopically lhe inner reLtnaE surface was thrown into
folds ibal gave a railroad Ir.ick-like reflex runnjn^j Ihroughoul
much of lhe posterior fundus of the right eye and to a lesser
degjee in the Teft eye (f). In (he righf е Уе there- was cysloid
m acular edema and a fine pallern of superficial reLtnaE cysts
tEiaL defended throughout the m acular area. Fluorescein angi­
ography showed some improvement in the dye leakage from
lhe г+itinal ci]pil.laries It.] and Hj. Angiography of lhe left eye
was normal except for evidence of Eoca.1 si:ars relaled Lo cen ­
tral serous chorionetinopalhy. I-[is past n o d ical history Was
positive for diaEic4es and carpaE tunnel syndrome.
I: Note lhe same but lets prominent fundus t hanges in his
sisLer w h o had normal visual acuily.
|-L: The eyes of th-e mother, w h o had a history of right bemi-
anopia, optic disc cupping, and normal intraocular pres­
sures, wen? obtained aL auLopsy. fJrtrth examination of her
eyes revealed prom inon I lignl reflexes on Lhe surface of Lhe
rrjlina. ht]sl.t)patholoj^ic examination revealed ibickening anti
undulalion o f the internal I inciting membrane of the retina
(anriws, |-Lj, multiple superficial schisis cavities separating
lhe internal limiting membrane from lhe nerve ГзЕзег layer,
ganglion cell aLrophy, and cyslic spaces in the inner nuclear
layer. Plains for elastic tissue, amvloid, and mucopolvsaccha-
i ides w ere negative.
{ Л - C , Гго ггс ] X i : i - an d M r ii, U I A r tf tt f itjir t M l ' cI i l . iI A m 'Lu i j l i u n . ,\ l!
rtnf-rvcdi -^'i
O
■_/'
A S T E R O ID M A C U L A R D Y S T R O P H Y i . J 4 Asteroid macular dystrophy.

A—C : This 3fl-year-old black wom an com plained of mild

figure 5.34 ( A-С), depicts the ophthalmoscopic Hind angi­ visual changes. Family history and past medical history were
ographic findings in a young wortiati with a striking seven- normal. Visual acu ily was 2(У20. Ko1e the peculiar slfillate
point dark stellate figure centered in tbe fovea и Г both lei-itm, lonsislin^ til scvun fine* irregular dark lines- radiaL-
eyes.""1 Her vlsujt acuity was 20/20. !]er family history inj$ from 1he center of Lbe fovea in each eve. Angiography
was norm at. No family members were available for e lim i­ i- i ■=»: 11 i n I". df-1- i‘ nl . 111■l i in hi-. ?l 11: (.■ "i I in-11 m liiuhI
epithelium $КРЕ)-
nation. It is probable, however, lhal this is л foveomacular
dystrophy or dysgenesis with a good visual prognosis. Sjogren-Larssen syndrome^
0 and E: NoLe lhe yellow ish deposit and line crystalline
deposits in lhe m acula (D ] in this i t -month-old black b(]y
S jO G R E N - L A R S S O N S Y N D R O M E
wiLh mental and nwtor rstardalion, Echlhvosis, getjerdliled
Sjogren-Larsson syndrome, an autosomal-recessive neu- weakness, and spasticfly (Ek There was som e narrowing of
the re1in.il arterioles.
roculaneous syndrome, is characterized by the following
clinical features: { I ] congenita! ichthyosis; ( 2) congeni­ Aicardi's syndrome.
ta] Eow-grade stationary menial deficiency; [3j symmetric F—H: Two-year-old girl w ilh microphthalmos and orbital
spastic paresis with maximum involvement of the legs; (4) cysl, rif^ht Side; colohoma bf the . biPl ever absence ol" the
convulsions; (5) dental and osseous dysplasia; ( 6) defec­ corpus callosum ; hydrocephalus secondary ta aqueductal
HencKis; anti psvchomolor and mental retardation. The alro-
tive sweating; (7) hypertelorism; ( 8) reduced life expec­
phic fialchoh in the chom id and КИЕ w ere ncLucLed aL binl:
tancy; and (9) ophthalmoscopic changes in the macula, and w ere initially interpreted as possible chorioretinal scars
characterised by the presence о Г white glistening flecks and caused by cytom egalic inclusion disease.
yellowish pigmentary changes that may simulate best's
Flecked retina in Alports syndrome.
vitelhfbrm dystrophy (Figure 5.34E> and E )L 3t"l-1fi7 These
I - L This ЗО-уедг-old man, with hearing lost, anterior lE!r:Li-
macular changes are present in a majority of patients
conus fD:, and nephrilis, had m ultiple flecks in lhe m acular
and considered pathognomonic, ibe glistening dots are region h ol" ЕнмЬ eyes |E anrl F). Angiography (G ) revealed no
believed Lo be located in the inner retina (ganglion cells charges corresponding w ith Lhe flecks implying Lhe flecks lo
and inner plexifomi layer), may appear by age 1-2 years., be :n inner ratma rather Lhan aL th« КИЕ levrl. Hii- visual acu ­
and increase with age. Photophobia is often present. On ity was 20/25-. His elecLrorerinogram and efecLrtboculogram
fluorescein angiography die foveal and perifoveal areas were normfiL
show hyperfluorescence. The crystals do not block fluores­ 1 ■
' .iin: Ci tTMjrlL'sy mi' Dr. K.inclv L -.impjo: l i nirid 1. Гrum f.jiilicrL uL
I 9&Br А те гь с ^ Н h1tMJiL.il A s^ u i.L liu ri. ЛИ rig h n m'stjrvt.'tf.
cence, and are hyperautofluorescent.!":: In addition to the
crystals in inner retina, microcystoid spaces may he seen
on OCX a feature somewhat similar Lo idiopathic juxtafo-
veal telangiectasia type 2 .'"' Macular pigment Levels were
found to be reduced by macular pigmenL refleclometer
and aulofluorescent testing by Van der Veen el a l.: EiRC
and HOC done in a few of these palients are usually nor-
ma]:ifU f,!|..i,-|.J-- Patients with this syndrome are spe­
cifically deficient in the fatly aldehyde dehydrogenase
component of the fatty .alcohol oxidoreductase that cata­
lyzes the oxidation of medium- and long-chain fatly alde­
hydes to corresponding falLy acids, l his deficiency may be
detected in the skin fibroblasts of patients and in carriers
of Lhe disorder.-^
SjagretV-Ljirs^Qn Syndrome 3I 5

A IC A R D J- S S Y N D R O M E
]he cardinal features c f Aicardi's syndrome are infantile
spasms, agenesis of the corpus callosum, and a character­
istic chorioretinopathy that may occur in association with
other ocular abnormalities, including microphthalmia,
colobomas of the optic nerve and choroid, sclera! ectasia,
persistent pupillary membrane., and glial tissue extend­
ing from the oplic disc. ' ! i&* Other associated findings
are menlaE retardation, generali;ted seizures, hypotonia,
cerebral malformations including microcephaly, poly­
microgyria, periventricular and intraeortical gray-mailer
heterotopias, interventricular cysts, choroid plexus papil­
lomas and cysts., asymmetry of cerebral hemispheres, cor­
tical atropity, pineal gland cysts, vermian anomalies, and
cerebellar hypoplasia,14^ 5"-189 Costovertebral defects
such as scoliosis, hemivertebrae, block vertebrae, fused ver­
tebrae, and missing or bifurcated ribs and craniosyostosis
are common findings. Characteristic fundus lesions
are well-defined, circular, white lacunae with minimal
pigmentation al their borders varying in size from one-
tenth disc diameter lo twice the normal sих of the optic
disc {Figure 5.34F-H). Ihey are usually bilateral and are
often symmetrically distributed, hi general the lesions are
clustered around the oplic disc and decrease in size and
number as they extend into the periphery of the fundus,
fcleclrorelinography may be normal or minimally dis­
turbed. 11islopathologically these lesions have been shown
to correspond lo areas of depigmenlation and deficiency
in the RE'ti as well as gross choroidal 'atrophy^75'377'-331 it
is probable that the chorioretinal lesions represent a dys­
genesis and not a progressive dystrophic disorder since
new lesions do not occur. Progressive pigmentation of
the lesions has been documented. Aieardi's syndrome
occurs only in females, and no familial cases have been
reported excepL for one report of discordance in monozy­
gotic twins.1" ' It has been reported rarely in Klinefelter's
47,XXY males, except for one report in a 46,XV
та1е.Ли" No study so far has been able lo demonstrate
a defect in the X chromosome, hence it appears lhal the
change occurs after fertilization. Attempts lo find the
mutation in the Xp22 and the Xq2d regions have been
unsuccessful. ^ 1'37
A L P O R T S D IS E A S E ___________________
Alport syndrome is associated with genetic abnormality
involving the ОOL4A3. COI.4A4, and COL4A5 genes lhal
encode the production of type IV collagen, lhis protein is
common lo the basement membrane of the glomerulus,
cochlea, retina, lens capsule, and cornea. The glomerular
basement membrane is irregularly thickened and splinted
and stretched. The immunohistochemical stain shows
absence of A5 chain. Carrier females may have variable
inactivation of the X chromosome in different tissues and
may manifest some of the featunafLMa,3M Ihese patients
j. IS Macular hole (n Al port’s syndrome.
A and B: A 34-year-old male w h o had a history of rartal
Lransp3ant Lind tearing fuss. H e showed several flecks a I the
posterior pole, characteristic. fur Alport's h-yndmme. H e вцЬ'г
sequenlly developed a Iraumatic cataract requiring cataracl
surgery wiLh ini ra ocular lens placeman). Following Lhis, lie
was found to have several small holers in the m aC u li Lhal
became cun fluent into a Solitary giati} htde,
С Hind E): Left eve of another patient with inner №tinal Ifecks
Lhat eventually developed а lar^e macular hole.
E—I: A 22-year-uld Indian m ale had progressive -decrease in
vision m bolh eyes assucialed wiLh worsening тепа] insuffi­
ciency and deafness. His parents and sisler were asympljom-
alic. His visual acuitv was 1<У50 and 2Q/64D. Bilateral anterior
lunLiconus with localized cataract due lo microbreak!; ir>
capsule was present \b and Fi. UilrHeral symmetrical macular
flccks wore seen in Ilie superficial retina, likely at the level of
the internal limiting membrane, suggesting abnormalities of
the footplates of M uller cells IG and HI1. O ptical coherence
tomography demonstrates the flecks lo be at the internal lim­
iting mon'ibmne and just beneath it. Visual acutLy returned lo
20/20 in both eyre following cnlaracl Surjjety.
■. V ( . l i u rlc:;-y Lil l>r. ! J . i v k E W l iritH irH - 4 tm .. W in n l i i h:i , t i I i v k t k и J. l!u -
htcCin.il ЛИ ,ib, S.tuntlurs J 0 LC1, V 7 t i - Q - 7Q 2 Q- i |j. L1 2 .
prftftent with hematuria, deafness, and progressive renal
dysfunction, ihe condition was first described by Cecil
AJporL in 1927. The frequency' is 1:5000. it accounts for
2. 1% of end-stage renal disease in pediatric patients. ЯйВД»
of affected patients are male. Affected males are more
likely to be deaf and develop renal failure than females.
]l is associated with the following ocular findings:
mJcraspherophakia; lenticonus [Figure 5.35E and K);
anterior or posterior suhcapsular cataracts, posterior poly­
morphous comeal dystrophy; multiple, small (20-50 pm
in diameter], punclaLe, yellow-whiLe lesions in the super­
ficial pericentral retina in the macula (Figures 5.34|, К
and 3.35A and С, С and If); and confluent and clustered,
punctate, yelloiv-white lesions located deep lo the retinal
vessels in the midpcriphery of tEie fundi. ‘0Ll" L1,1 '1Ъе mac­
ular lesions may be present in early childhood but prob­
ably become in оre apparent with age and are seen in
35% of p a tie n ts .T h e y are nol associated with angio­
graphic or electrophysiologic changes other than that
whicit may occur as a result of hypertension and renal
faiJure.-l0‘l-‘ul£^ ?M|,'UN I here may be spotty areas of win­
dow defects in the RPE associated with the peripheral
lesions."" The nature of these lesions is unknown. These
patienls are known to develop giant macular holes likely
due lo defective Muller cell basement membrane (figure
5.35A-D).,lL'' The anterior lenticonus is pathognomonic
for Alport syndrome. Posterior polymorphous corneal dys­
trophy due to defect in the Descemet's membrane occurs
infrequently. I?rusen in Bruch's membrane, degeneration
of the ItP E in the macular area, and serous retinal detach­
ments occurring in the terminal stage of renal insufficiency
have also been reported in these patients.
 Because these patients have abnormalities affecting
basement membranes elsewhere, particularly that of the
renal gjomeruli, it is possible Lhal the mid peripheral
lesions may represent nodular thickening of the base­
ment membrane of the RVb. (basaE laminar drusen' see
chapter 3], and that the superficial lesions in the macula
are related to abnormalities of the basement membrane
of the Muller cells or retinaE astrocytes. Cehrs et al. have
suggested that the retinal flecks may consist of an abnor­
mal subtype alpha 5 of type IV collagen, which is a major
structural component of the glomerulus basement mem­
brane.'^ lhe gene encoding for this protein has been
Localized to the same locus (C G I 45A ) at XqlZ, where
genetic linkage studies have placed the defect in patients
with X-tinked Alport syndrome.-111. Mutations in collagen
type IV genes have been described to be responsible for
X-1inked [COL4A5)j autosomal-recessive, and. autosomal -
dominanl Alport syndrome tCOlAA3fCOL4A4), A related
disorder benign familial hematuria, is an aulosomal-
dominanl disorder: about 40°ю of these cases cosegre-
gate with the COL4A3/COL4A4 loci the same site for
autosomal -dominant Alport syndrome. It is likely lhal
some cases of benign familial hematuria may represent
the carrier state for autosomal -recessive Alport syndrome.
Collagen type IV nephropathy is an entity in itself, and
phenotypic manifestations of <ZOL4A3fCOLAA4 muta­
tions may range from monosymptomatic hematuria
(benign familial hematuria] to severe renal failure {Alporl
syndrome), depending on the gene dosage.'1' '
R ET IN A L D Y S T R O P H Y IN
D U C H E N N E A N D B EC K ER
M U SC U LA R D YSTRO PH Y
Duriienne muscular dystrophy is a lethal X-linked reces­
sive disorder characterized by progressive proximal mus­
cular weakness, loss of ambulation, and early death.
Ninety-five percent of patients are wheelchair-bound
by age 12 years and the mortality rate is 95°/b by age 20
years. I"he dystrophin gene for lhe disorder is mapped lo
Xp21. E>yslropbin, lhe gene product of Duchenne mus­
cular dystrophy is a 427-kDa sub membranous cytoskel-
elal protein and many dystrophin-associated proteins,
such as utrophin, dystroglyeans, sarcoglycans, syntrophins
and dystrobrevins. have been identified. Dystrophin and
dystrophin-associated proteins are very important pro­
teins for skeletal, cardiac, and smooth muscles and also
for the peripheral and central nervous syslem. including
the retina. Dystrophin and bela-dystroglycan localize al
the retinal photoreceptor terminal; their deficiency results
in abnormal neurolransmission between photoreceptor
cells and ON bipolar cells, [dystrophin has seven isoforms
in variable tissues, and the retina contains full-lenglh dys-
Lrophin (Dp427), Dp260, anti Dp7L Dp7l localizes in
the inner limiting membrane and around the blood ves-
selsr and Dp260 is expressed in the outer plexiform layer
5жЗЬ Fleck retina in ring 17 chromosome^
A —D: This 34-year-old man had short slalure, m icroceph­
aly, cafe-au-lait spots, mild mental deficiency, yellow flecks
Lhroughoul the postequalorial fundi ГА and B), and ring 17
chromosomc; (D). had no visual рсм^пгаайпIs. His visual
Eicuily was 20/30 hi laterally. There w ere a few cortical flecks
in both lenses. Fluorescein angiography revealed a saEt-and-
popper pattern of ffibtLEed hypertluqrescence and nun fluores­
cence corresponding w ilh the llecks I Cl). H is chromosome
diiLi^nosit was-tb,XY,ri 17; Ip I $^25}, thsJ o f a majet wiLh nn^
17 chronidsoni c\ His Family history was гьс^д I i ve.
Benign flcck retina^
E Lind F: This asymptomatic yuung Australian Abui]j;ine
wtnniin had л о гтл ! visual acuily, colur vision, And d e t-
Lrormino^raphic findings. There w ore Widespread poly­
morphous. flecks at the level o f the pigment epitheEium
throughout lhe peripheral fundi. The family history was nega­
tive. N o other family members were avai fable for гоатЗпа-
Lion. NuLe Himilarilv lo Figure .i.Jtit?.
It is generally assumed that dystrophin functions Lo sta­
bilize muscle J'Lbers with dystrophin-associated proteins
by linking lhe sarcolemma Lo the basement membrane
in muscles, but its function in the retina is unknown so
far. i’alienls with Duchenne muscular dystrophy have
subnormal scotopic LRG amplitudes in the form of elec­
tronegative b-waves; tbe ex lent is likely determined by
tbe presence of, and location of, lhe gene deletion .'1,e"121
J:ocal hype rpigme mat ion of the macula may be seen, but
color vision, pholopic EiRCs, visual acuily, and exlraocular
muscle function remain normal, distinguishing EDuchetme
muscular dystrophy from other X-linked disorders wilh
electronegative EiRCs.'^
O C C U LT M A C U LA R D YSTRO PH Y
Occult Hereditary Macular Dystrophy
Miyake et aL423 described Lhree patients in two generations
wilh progressive central visual loss, normal fundus and
fluorescein angiographic findings, mild or moderate color
vision defects, normal full-field ILRG, and severely affected
macular ll is an autosomal-dominant disorder
wilh age of presentation between 20 and 45 years, ihough
an 1 1 and a 16-year-old patient have been described.i2fr
-
Since the original description, lhe spectrum of visual loss
and progression has widened. The presenting visual acuity
is from 20/20 to 20/200. Color vision is variably affected,
bome patients may show no progression of visual loss or
change in their central scotoma, while the majority show
worsening central vision.10^ M u lt if o c a l ERG and more
recently OCE' have been useful in confirming the fi|jd-
i n g s . ’■|1: All patients show fovea! cone involve­
ment: some show variable involvement of fovea I rods, ihe
characle risitic m L i l l i focal ElfcG finding is decreased ampli­
tudes in the central ring or hexagons, with amplitudes
 \

т r 5 w — ш

®
returning to lhe control values as one moves eccentrically
towards lhe peripheral hexagon s.'1J|,,k' ’ 'Im p licit limes, Ш
additionr have been found to be delayed in доте studies,
suggesting involvement of more anterior retinal elements
than cones aione. OCJJ' shows Variable thinning of the outer
nuclear layer in most eyes, though some eyes wilh poor
cone function have normal outer nuclear thickness, sug­
gesting functional rather ihan structural laas.JJSjl3a [hough
the early reports were from |apan, case series have been
described in Italy, the resl of Eiurope, and the LISA.'1iG "451 1
No specific gene defect has so far been implicated.
Sporadic Occult Macular Dystrophy
A clinical and elect rophysiologic appearance identical to
the heredifary form of ocoilt macular dytrophy has been
seen in patienls wilh no family history suggesting the dis­
order may have multiple etiologies or has variable pene­
trance.' ' Patients with autoimmune antibodies to enolase
or other retinal elements can presenl wilh central sco-
Loma, cone dysfunction, and normal fundus anti fluores­
cein appearance.111 A careful history of the age at onset of
symptoms, progression, and any associated autoimmune
disease may help differentiate Lhese patienls from occult
macular dystrophy.
U N C L A S S IF IE D M A C U L A R
D Y S T R O P H IE S
Patients with a variety of nonspecific patterns of atrophic
macular dystrophy unassociated wilh flecks, angiographic
evidence of lipofuscin storage, or other elect rophysio-
Logic or systemic manifestations are occasionally encoun­
tered.'114 Jn such patients the author prefers Lo label their
macular dystrophy as "unclassified” ralher than Stargardfs
disease.
F LEC K ED R E T IN A A S S O C IA T E D
W IT H C AFE-AU-LAIT SPO T S,
M IC R O C E P H A L Y EPILEPSY,
S H O R T STATURE, A N D R IN G 17
CH RO M O SO M E
A ring chromosome is a type of deletion lhal results from
breakage and loss in the terminal ends of each arm of a
chromosome, followed by union of the broken ends
(figure 5.36D). Patients with ring 17 chromosome may
have menial deficiency, seizures, short stature, micro­
cephaly, and cafe-au-lait spots and demonstrate a striking
pattern of yellow flecks at the level of the RPr throughout
the posterior fundus (Kigure 5.36A and u ).‘n6-'1 None
of these patients has cutaneous neurofibromas, Lisch iris
^.■Sb Continued
G - L This 42-yeaг-old Hispanic wom an was sesm for inter­
mittent blurred viKiorr in bolh eyes. Shy was hospitalised tor
acute myeloid leukemia and had received prednisone, cyta-
rabjn, da jnorubicin, vincrihlinu, m Ш hotruKate, and radia-
lion. Htrr vision was 2Й/2Й in both eyes with Й6гта1 color
vision. Both Eundi had sym m etrical appearance o f flecks lhal
w ere smaller in Lhe posterior pole resembling those of lun-
duii flavimacjulaluH and larger Low;trds lh e m idperfchray and
e ® e (* fc d anterior Co I ho equator- There w h * no known family
history: she succum bed Lo her illness and lhtL eyes could no1
I)u obtained for bis-l o]o£>y. The tundus appearance Was typical
cl" familial betligfl fleck reLina and nol s e c o n d ly lo Joukumia
or Ihe? effects o f her inedica liens.
t ,in d F-, In im M l Л IJis In г l 'I iiji 1 L i- L , l :u u rlrji.v ц| l>r. iV.uhut'] CJber.
К .1 IhiJ L, АЗьо, Y iin n u j'ii, L jw rirn i.4! I. Ih u i n.:l A ll л .. Sju n ck rci 24JJO ,
p .F JS .'i
nodules, or a family history of neurofibromatosis. I heir
chromosome diagnosis is 46,XYrr[l7 ) fpl3q23). Although
the Nh'-J gene has been mapped lo chromosome 17, it
is unlikely that Lhese patients have N F-I. The fluorescein
angiographic findings in one case suggest that the fiecks
are associated wilh irregular depigmentation or thinning
of (he FEFE as well as focal obsl ruction of the background
fluorescence by some of the flecks (Figure Ъ.ЗбС).'5-''
Charles et al.436 found some evidence of blockage of cho­
roidal fluorescence by lhe fiecks. which Were believed to
be at lhe level of Lhe pigment epithelium. Although the
fiecks resemble drusen, their poor correlation wilh foci of
discrete hyperfluorescence suggests they have a different
morphology.
B E N IG N F A M IL IA L FLEC K R ET IN A
Sabel Aish and Dajani-110 and later, McAllister et аМЛ:>and
Audo et al.,'1"11 reported a beautiful pattern of somewhat
polymorphous white flecks scattered wideLy throughout
the fundi unassociated wilh any visual deficit or eleclro-
physiologjc deficits [E'igure 5.361-1-[.J. ]he flecks appear
round posteriorly but become more polygonal towards
the equator and periphery ( figure 5.36К and Lj. ihere is
a suggestion Lhe shape follows the choroidal venous lob­
ular pattern especially beyond the arcades (Figure 5.36H
and i). The fiecks are hyperautofluorescent, suggesting
accumulation of fluorphores wilhin the KFE .1,1 No pro­
gressive changes in the flecks, the RPE, or photoreceptor
function have been described to dale and lhe condition
remains benign, 'lhe pattern of fiecks appears similar lo
that reported by Miyake and Нага da"*42 in three patients
in uvo families with congenital sLaLionary night blindness.
4wo of their patienls had absent scotopic EftG responses,
subnormal Ep G responses, and delayed dark adaptation.
C O N G E N IT A L S T A T IO N A R Y
N IG H T - B L IN D IN G D IS E A S E S
Congenital, nonprogressive. ni^ht-blindiny diseases are
characterized by infantile onset of nyctalopia without
progression and good visual acuity. These patients can be
subdivided into two groups: those with nonna!-appearing
fundi and those of a distinctive fundus abnormality.
Normal Fundus
Autosomal -dominant {absent scotopic TRG, Riggs type;
type L)
1. rhodopsin mutation (ЯН О }
2. & subunit of rod transducin ( C j'jV A J '2 , Nougaret)
3. \ 'a subunit of rod c G M P phosphodiesterase G il)
X-l inked (negative HRG, Schubert-Bornshein. type tl)
1. E.-type calcium channel {САСЛ/ДЗР} incomplete
X-linked stationary night blindness
2. Unidentified gene Xpl 1.4-11.3 complete X-Eiliked sta­
tionary night blindness.
Abnormal Fundus
Autosoma L-recessive
1. Arrestin (&4C: QguchiJ
2. Rhodopsin kinase [ЯМОА: Oguchi)
3. 11-ris retinol! dehydrogenase (KDH5: fundus
albipunctatusj.
Autosoma I-Do m ina nt Co nge n ita 1
Stationary Night Blindness
AutosomaL-dominant patients haV( normal visual acu­
ity and classically show a reduced but normal -appearing
photopic response, and poor or absent amplitudes under
sco topi с conditions, lhis type of ERG response in con­
genital station ary night, blindness is referred lo as the Higgs
response.'1'1'1 fro longed dark adaptation does noL improve
the scotopic ERG amplitudes. Some pedigrees, however,
may show a Schubert-llomscbein-lype response (electro­
negative ERG) that is more frequently observed in reces­
sive and X-l inked pedigrees of congenital stationary night
blindness.
R H O M utation
'three different missense changes nave been found in
the rhodopsin gene so far: GlyUOAsp, ]frh>4lle, and
Ala292Glu. The night Ы indness remains stationary in most
patients, but san e with GlyDOAsp mutation may develop a
few bone spicule pigmentary change, mild vascular attenu­
ation, and constriction of their peripheral visual field after
age 35. Mild late cone disfunction in ay also occur
Afphn Subunit o f Transducin M utation: N ougaret
Type
Transducin mediates the second step in the phototrans-
duclion cascade; pholoaclivated rhodopsin interacts wiffi
the alpha subunit of transducin. The only known disease
causing mutation is Gly33Asp change, '['he cones have sub­
normal sensitivity and need 10 times more intense stimu­
lation, there is a rod-cone break in dark adaptation, and
the rods show a mild response under veiy bright flashes.
'Ihe mechanism for this response is not understood. 'L'hese
patients Ьач'е a normal fundus appearance throughout life.
Beta Su b u n it oi R o d cC M P P h o sp h o d iestera se:
Ram busch Type
Jtod cGMP phosphodiesterase, the third member of the pho­
to transduction cascade, is composed of one ft, one X and
two i subunits, lhe change in the .1 subunit is a l]is25tiAsp.
which results in alteration of cGMP concentration affecting
impulse transmission. Their fundi remain normal.
Autosomal-Recessive and Simplex
Congenital Stationary Night Blindness
Autosomal-recessive and simplex palients may have nor­
mal or moderately reduced visual acuity and most are
myopic. The LRG typically shows a progressive increase
in the negative response [a-wave) during dark adaptalion.
buL no similar increase in the positive response (b-wave).
lhis electronegative ERG in congenital slationaiy night
blindness is referred to as the Schubert-Slornsc he in type
and it may occur in X-l inked as well as recessive pedi­
g r e e s . Miyake et aI. further subdivided this group of
patients based on the evaluation of the rod ERG and/
or psychophysical dark adaptation: one group [complete
type) lacked rod function, and the other group (incom­
plete type] showed evidence of rod function.11-1
Х-Linked Congenital Stationary Night
filirjdness
these patients arc usually myopic and most have sub­
normal visual acuity. The fundi are unremarkable other
ttp i for myopic chadgeii^5-^ LlectroFetinographic
changes include normal to near-norm aI photopic
responses and a barely recordable or un recordable scoto-
pic r e s p o n s e . D a r k adaptation sltidies typically
show elevated rod thresholds. deduced amplitude of oscil­
latory potentials of the EiRG occurs in most patients'14 as
well as in female carriers of the X-linked Most
heterozygous (carrier) females in families with X-!inked
congenital stationary night blindness are asymptomatic,
'['hose with symptoms and eleclrophysiologic evidence of
the disorder are nearly all daughters of asymptomatic car­
rier mothers.-1''' Daughters of affected males rarely show
signs or symptoms of congenital stationary night blind­
ness. Uneven X-chromosomal I ionization is the most
likely reason for females manifesting this disorder. The
gene locus of this disorder has been found on the short
arm of the X chromosome proximal lo the DXS7 locus/1"
the region between 01C and TJJvJJ1 on tbe short arm of the
X chromosome/1^ and distal lo lj.28 at Xp2L4b|'
Patients with congenital stationary nighl b Eind ness may
present with infantile blindness with a markedly subnor­
mal photopic and scotopic l:RG.J " Ibis may incorrectly
suggest lhe diagnosis of liber's congenital amaurosis.
Visual responsiveness as measured by TRG lakes 6-12
months to mature fully. En congenital stationary night
blindness visual improvement during ptiotopic conditions
in these patients may be dramatic during the first year of
life. Serial liIJGs to detect evidence of this improvement
may be helpful in some Cntses.
Oguchi's disease, fundus albipunctatus,. and Kandorfs
disease are disorders in which congeniLal stationary night
blindness is associated wilh fundus changes.
Oguchi's Disease ^>.17 О guch Vs d i&ea se,

Oguchi's disease is one form of congenital stationary A - F : This 4b-year-old black wom an had normal visual аш -
iI y. Note lhe golden color of lhe fundus in I he? I ighL-ndaf >k’d
night blindness in patients wilh normal visual acuity,
sLale iA—L». Her ehHJtro-ocularyraphtc findings w ere normal.
visual fields, and color vision .1,'-i:=
E-|6j Ophthalmoscopy The electrorelinogram showed depression of I I k - b-^vivo <md
in the light-adapted Elate reveals either a green ish-white reduced rod function, w jglotffaphy 'Lj W lIS normal. Fundus
or a golden-yellow color lo the fundus [Figure 5.37A phologTaphs i.F i o f lhe light eye following I hour of dark
and II]. It may be confined to the posterior pole or lo the adaptation. Note Lhe color of Lhe retinal pigment epithelium
periphery., or it may involve both. The densily of lhese is normal.
(1РЁ changes obscures lhe details of lhe choroidal vascu­
lature. 'lhe retinal vessels stand out in hold relief, and lhe
color of the arteries and veins may be similar. The fundus
color vision are normal, i-undoscopic exa mi nation reveals
achieves a normal color in from 30 minutes to several
a Eaige number of discrete, small, punctate, while spots
hours after dark adaptation (Mizuo phenomenon) (f;igure
at Lhe level of the RPh (Figure 5.33).-,l:il_-"'4 These lesions
5.37b] fluorescein angiography yields normal
have their maximum density in Lhe poslequatorial region,
results (figure 5.37E). Dark adaptation shows a delayed
but the center of (he macula is usually spared (Figure
secondary adaptation (type 1} or, rarely absence of sec­
5.3S). 'lhe spols generally increase in number over the
ondary adaptation (type II). The EftG shows subnormal
уИ(Т& 469 but some spots can disappear over time in older
rod responses that usually persist after prolonged adap­
people.1'1"'1 2 Lhe disc and retinal vessels are normal. Ilte
tation. Oguchi's disease is similar to fundus alhipunclate
liRG is usually normal, but when it is abnormal, it usually
dystrophy in that there is reversibility of the psychophysi­
improves toward normal levels after prolonged adaptation.
cal function following prolonged dark adaptation, but
Ibe L-.OG may be subnormal but becomes normal after
si is different from X-linked congenital slalionary night
prolonged dark adaptation. The dark adaptation thresh­
blindness associated wilh myopia, in which this adapta­
olds are markedly elevated but return lo normal absolute
tion does not occur. Histopathologic studies have revealed
threshold levels if the lest is continued for several hours
abnormally Large cones in an area that extends 20a tem­
or longer.1v-' Overnight patching of the eyes prior to elec-
poral from the optic disc and an additional layer of gran­
irophysiological tests is a useful way lo achieve prolonged
ular pigment between the photoreceptors and the true
dark adaptation. Fluorescein angiography reveals a mottled
KPH."’1'0 Yamanaka'MlJ failed lo find evidence of a distinct
pattern of fluorescence throughout the mid periphery of the
Layer between the JJPK and lhe receptors. Ue Jong el al. in
fundus, in general there is no correlation between the areas
four patients wilh X-Linked relinoschisis postulated (hat
of hyperfluoreseenee and the white spots. Angiography
the Mizuo-Nakamura phenomenon may be caused by an
may demonstrate changes in the RPli in the macular area,
excess of exlmcellular potassium in the retina as a result
and occasionally a few patients may lose central vision
of a decreased potassium-scavenging capacity of retinal
because of a cone dystrophy or atrophic maculopathy
Muller eeEls.lc0
(Figure 5.38B and С).-*-*7* 'lhe flecks are not hyperauto-
'ibis disease is inherited as an autosomal-recessive trait
fluorescent suggesting that these changes may not be al the
and mutations have been identified moslly in the arreslin
pigment epithelial level but rather in (he outer part of the
gene and occasionally in the rhodopsin kinase gene.^4,465
pholoreceptor layer. High-definition OCT con firms that
A golden sheen confined lo the macular area and the
the flecks correspond to dome-shaped opacifications al the
Mizub phenomenon may occur in some paLienls wilh pro­
pholoreceptor outer-segment layer and continuous with
gressive, lale-onsel X.-1inked cone dystrophy (Figure 5.32J-E.)
the RPF cells.■;‘l 'lhe disease demonstrates an autosomal-
and X-l inked relinoschisis. 4'''
recessive inheritance with the gene defect in П -cfs retinol
dehydrogenase (R D ILS), the enzyme found in the RPti
Non progressive Albipunctale Dystrophy cells responsible for the production of 11-cej retinal, which
is transported Lo the rods and cones lo act as the chromo-
(Fundus Albipunctatus) phore in rhodopsin and cone opsins.1*75^76 A total of 19
Patients with nonprogressive albipunctate dystrophy com­ different mutations have been found Lhus far in patients
plain of night blindness. Visual acuity visual fields, and wilh fundus alhipunctatus.
 '17115 typically nonprogresstve form of lhe disease is
more common than Its counterpart, R[TA ...... '' (see Mguie
5.3HES-D) nind Bothnia (I'igure 5.44) and Newfoundland
rod-cone dystrophy (Figure 5.45). Differentiation of
these two diseases in younger patients may be difficult/"
Occasionally both forms of the disease may occur in the
same family.” '-'tdu RPA shows progressive nyctalopia,
hone corpuscular pigment change, and vascular narrowing
beginning by the third decade. Some patients, especially
from ]apan 0ф -4Э%), have a macular or cone dystrophy
in addition lo the fecks of fundus albipunctalus, all of
whom have mutations in the tfD H j gene of fundus aEbi-
punclatus.‘j7i,',S]^lil4 Most, but not all, patients with macu­
lar involvement were older; whether this is a function of
Longer duration of disorder or а с о ш ф п Japanese ances­
tor in these various families remains to be determined.'1"'
lhis macular change associated with decreased cone LRG
amplitudes resembles the macular change seen in patients
with Bothnia dystrophy; however (he gene defecLs in the
two conditions are different {see section on llothnia dys­
trophy below). Et is conceivable the metabolic derange­
ments caused by the two mutations have some similarity
or overlap, given that they are both involved in the metab­
olism of 1] -tt's retinol.
Fundus albipunctalus should be differentiated E'rom
acquired nyctalopia associated with vitamin A deficiency
(Figure as weLl as crystalline retinal dystro­
phy (see Hgure 5.46), oxalosis (see Figure 5.67}, cysti-
nosis (see Figure 5.64), canthалаnthine retinopathy (see
Figure ^.10), basat laminar drusen (see figure 3.31 and
3.32), and Alport's syndrome (Figure 5.35). [Ydigrees with
larger "scale” or '"silkworm-shaped'’ flecks w ith 1"'11 or with­
o u t'"' 1,11 similar electrophysio logic findings may represent
variants of albipunctale dystrophy (i'igure 5.3SO), Llayashi
et al. found compound heterozygous mutations p.VI77G
and p.[.31UdelinsE:V in the RDH5 gene in a 3-year-old pro­
band with night blindness and fundus changes similar lo
benign fleck retina.""*' His asymptomatic parents and one
of the grandparents each carried one of the mutations,
explaining the autosomal-recessive inheritance.
5.1Й Fu nd us a Ehip uпс latu s.
A and B: This 14-year-old female had normal vision, normal
eleclroretinogram, and &n aEjnormaL eleclro-oculoiyam . The
centre I and peripheral visual1 fields w ere normal. Dark adap­
tation studies revealed absence ol rod vision. Small punctate
opacilies exlendcd almost to the ara serrata (A a n d hS;. Two
brothers, 15 and 17 years o f age, had similar findings. Al! lhe
palienls were niyhl-Eilind. A 12-year-old sisler hafl normal
eyes. Angiography revealed a mottled paLLem o f byperfluo-
tescence indicative o f depiym enlation o f Lhe r e L i n a l piemen!
epilholium - everywhere excepL in lhe macular area.
5 o m eo f Lhe punctate spots o b s c u r e d choroidal fluorescence,
whereas others did nol.
t : Fundus albjpundM us in a 33-year-old man with bilateral
macular dystrophy. H it visual acuity was 2CJ/40 in f>oth
eyes. His erectro-oculographic findings w ere normal. H is
electroretinogram showed moderately abnormal rad and
normal cone funclion. After 50 minules of d a r k a d a p L a l i o n
Lhe eiectroreti nayram was normal. His FamsworLh-Munsell
100-hue test revealed a blue-yelltjw defect. Angiography
showed evidence erf biPt. atrophy in Ibe m a c u l a .
Hereditary stationary night blindness with
polymorphous flecked retina,
D : Large w hile flecks confined Kj Ihe peripheral fundi of an
1 1-year-old yirl w ilh lamilia! stationary night blindness. Note
similarity lo figure 5.36E--L..
E to K: The parents of this now 33 year old wom an, (sec­
ond of 3 sibling^! noted a visual behavior in lhe dark differ­
ent from her older sister w hen she was 3-5 years of aye. Her
vision was 2 0/20 in each eye aL age 33, fundus showed sym-
melric appearance of several punctate w hile doLs distributee
up lo the periphery and a bull's eye m aculopathy (E to Lj. Гhe
visual funclion with stationary niyhl blindness and fundus
appearance was unchanged 0 years laler I] and KJ.
LJ, flrfim V iiy .ih u . r id H .ir.ic L v 1""I
Kandori's Flecked Retina
Kandori's flecked retina3*9^ 1' is an apparently rare, atypi­
cal type of congenital non progressive nij^ht blindness; it
was described in four patients with sharply defined., dirty
yellow, irregular relatively large tlecks or patches of RX’E
atrophy distributed in the equatorial region between the
macula and the equator. The macula Was un involved. ’['he
relinal vessels and optic nerve were norma], Dark adapta­
tion was delayed but returned Lo normal in 30-40 min­
utes. Visual acuity, visual fields, hOtJ., EiRG., and visual
evoked potentials were norma!. Huorescetn angiography
showed evidence of foes] depigmenlation of the К I11: cor­
responding with the peripheral lesions. None of the four
patients was from the same family. I he flecks in these
patients appear similar to, if not identical to, congenital
grouped a Ibinotic RP1: spots, th is is believed to be л con­
genital anomaly of the ЙЙ0 that is usually unassociated
With night blindness (see Rgure 12.05-).
R E T IN IT IS P IG M E N T O S A
(R O D - C O N E D Y S T R O P H IE S )
Retinitis pigmentosa, tapetoretinal dystrophy; and primary
pigmentary retinal dystrophy are names used interchange­
ably to refer to a targe spectrum of disorders of variable
age of onset, rale of progression, severity, and mode of
inheritance. Ihese can be subdivided into two jbroajd cat­
egories: typical and atypical.
Typical Retinitis Pigmentosa
■'Typical retinitis pigmentosa" is used lo refer Co those
patients wilh a hereditary dystrophy characterized by the
onset of night blindness in childhood or young adult­
hood, progressi4,e contradio n of the peripheral visual field
beginning as a mid zonal ring scotoma with preservation
of central vision, and frequently profound visual loss or
blindness in middle or laler life [figures 5.35-5.41 533
liarly in the course of (he disease the (post common pre­
senting complaints are headache (5 3 % ) and photopsias
(35%). u Pholopsias are spontaneous impulses eshita­
tted by dying or disintegrating photoreceptors.. Tat tents
describe them as tiny blinking or shimmering lights or
gold sparkles. A total of 10-15% of palienls may not be
aware of symptoms unlil central vision is affected. Iliey
experience variability in their visual function and may
note worsening of vision during stress, 'ihere is a high
incidence of relative myopia,4*2 'Ihe earliest fundoscopic
changes consist of gray-green discoloration of the RPE
giving a tapetal-like reflex, depigmentation of the RPE*
mild narrowing of the peripheral retinal blood vessels,
and migration of pigment inlo the overlying retina in
a bone spicule pattern in a mid peripheral annular zone
i.S 'J Retinitis pigmenlosaL
A—D: Cystoid macular edema in an 8-year-old bay wilh
nyctalopia. Nole thy na*rawing of Ihe reinal arterioles iA..
Visual acuity №9; 20/30. His eluctmreNnoymm Wa$ exlin-
HLiihhtjd. Гhe fififlilphery bf the fundus ■LJ.i showed milrl Еюпе
corpuscular pigmentary changes, Early angiography (Q
revealed evfdfence of generalized detjJ|JmenfcsUQn af Ihe reLi-
nal pi^mf.'nl ppirhehUjfh.. Нфе the tic^jfltiftrescenl trass in the
fovGdla? апиа. This it proljably caused by cenJral compres­
sion of ihe rrrtinal хм п I hophyl-lfit pE^nionl by the lar^'j cenltal
relinal cv'sls. One-hoLrr anjjjpjbyrarfi ■L?l г е к л Ы minimal ejtf-
doncu ol sLaifl I ntt in the macula.
E and F: Widespread retinal edema and cysloid macular
pdcrnH in a 4J-vear-o!d Worna# wilh ni^ht blindness, moder­
ate number of vilnt'ous col Is, and minimal inliarelinal pignwni
migration. Her electrnnetincgram was severplw abnormal bul
nol uxlin^uiuhed. Her sister had similar finding^.
11—1; rhis Э7-year-old man wilh an fl-yuar history of nyctalo­
pia deveJo :"-:i evidence cl retinal telan^ie* lasis irlc-ri ч I-. in
the Ji^ht eye in 19S54 |H and И-. Note niirrowin^ of the? relinal
vessels jCk Because of progressive exudalion he was treated
with IransscJeral cry ореху in II^У0.
J-L: t l jjv i' lopi: ioni : i' pcripbcral rotin.i 11■I or : i-■ and
subnet lna[ exudation occurred in the вуе of I his- рл I i uni
duong observation for typical lelinilis piujmenlosa, 1 + viLre-
ous and eyn jild m atular erloma. The rtVina] lo]an^iet:-
ta^is was not present at the lime of inilial eKamirralian al age
14 but de^'eloped at aye 13 years К . there иан eidensive
kwt.a^e of flurjrt'scein from retinal vessels in m acular and
pararnai ular Telina. The CKUtlatjon UL4in in К ttfiar&d крип-
tantfously (Л'ег a period of 2 years :L I. Ln spile of chrcjnic:
cysloid macular edema she maintained 20/40 visual acuity
during the IS years o f observation. She experienced gradual
loss ol peripheral vision. J-ier eleclroreLino^Tam was exJin-
gutshpd at the time fil initial exam ina!ion.
of both eyes. This annular zone progressively enlarges in
an anterior and posterior direction and is associated With
further attenuation of the retinal blood vessels, waxy pal­
lor of the optic disc, and the development of a glistening
reflex and crinkling of the inner retinal surface secondary
lo an epiretinal membrane. Ihe pallor of the oplic disc is
due to astroglial proliferation on the surface of the optic
disc. J&ztinaJ arterial and venular narrowing is a second­
ary phenomenon from retinal autoregulation, fxjss of
photoreceptors, the highest naetabolically active cells in
the retina, results in dilTusion of nutrients from the cho­
roidal capillary circulation into the timer retina reducing
the metabolic demand on the inner retina and consecu­
tively narrowing the retinal arteries and veins. Posterior
polar cataract and ftne vitreous opacities or cells often
develop.''" ihis adds to visual loss. Classically, the mac­
ula has been described as being relatively normal and
visual acuity is excellent until the later stages of the dis­
ease. Recent investigation has revealed that 50% or more
of patients at the lime of initial presentation w ill have
biomkroscopic and йЩмегарЫе evidence of macu­
lar changes, including cvstoid macular edema (figure
epiretinal mera-
brane,.410, ,L 1 jnd atrophic dunces, in the RPE. Some
degree of epiretinal membrane change in the macula is
evident hi most patients wilh retinitis pigmentosa.'""
Cystotd macular edema is visible bio microscopically in
fewer than 10°Ъ of parents, in the author's experience. '['he
high incidence of 70% in 5S patients studied retrospec­
tively by ]-et ken hour ant! associates'" probably reflects (he
fact thal patients with central visual Joss are more likely Lo
he referred for photographic studies. Iliose wilh cysloid
macular edema often have more cells than usual in the vit­
reous. Although the incidence of eystoid macular edema
probably is higher in younger patienls showing minimal
pigment migration into the relina, it may occur in ail age
groups and in patients with typical pigmentary changes. In
most patienls with subtle macular edema that is evident
only angiograpbtcally in the paracentral area, visual acuily
is good. By the time cysts become visible bio microscopi­
cally, die patients are complaining о floss of central Vision
and the acuity is usually 20/40 or less. Some patients with
chronic macular edema may letain good visual acuity for
many years (figure 5.42A-D). Most patienls wilh macular
edema have 1+ or 2+ vitreous cells. E.oss of bnellen acuily
in some patienls is associated wilh atrophic WfE. changes
in lhe macula. This appears Lo occur more often in black
patients than while palienLs.Hfl
j.40 Retinitis pignienlosa with Coats'-type response.
A and B: This 40-year-old wom an from Iraq com plained of
difficulty SEiein^ a I nif^ht for mo№ than а у wars. Her visual
acuily was 20/20 in each eye. Visual fields; w ere narrowed
lo catft ГаI 20“ in e a d i nyu. LSolli up! к nerves w ere pale, Lhe
vessels were diffusely narrowed, the retEnaf pigment epithe-
I]Lin? was alrcsphac everywhere tisocepl lhe rr>ScUJa and Еюпе
spicule pigment migration spared [he гпасиЕа^ typical of reti­
nal iu p igmenlosa (A and E3:-.
С and D : This 37-yenr-old man with an tt-уенг history of nyc­
talopia developed evidence of relina I teEangiectasis inferfody
in ibe righl eye in IUS4 (C and L3). h:ole narrowing of ibe ret­
inal vessels. ВеСДЙВй of progressiva ex:idalion be was 1шакчЗ
with ЬгагкнгТеfal с г у и р и у in 199Q;
E anti F: Devtflopmtinl of peripheral reLinaJ t^langiectAS^
and nuLjietinal exudation occurred in the fifth* eye of this
patient durinjj] oireervalion for Гурjjc л I retinilis pigmentosa,
2 + vitreous cells, and cysloid macular edema. The retinal
lelangiectasis was not present a I lhe Lime of miLial examina­
tion al йде 14 but davelopEid aL age Ifi yeeis ;Ы. There was
Extensive leakage d flu q ie s te in from retinal vessels in m acu­
lar and paramaculiH retina. The exudation seen in I. cleared
Spontaneously over a pwit?d of 3 years (FJ. In spile of chronit
cysloid macular edema she maintained 20/40 vasual acuity
during the IS years o f observation, ib e experienced gradual
Id s of peripheral vision, h e r electroretinogjam was extin­
guished at ibe time of initial exam ma1 ion.
 Kluorescein angiography often shoe's evidence of reti­
nal and oplic nerve capillary «illdiLLo ii. angiographic evi­
dence of retinal capillary leakage may be confined Lo the
macular area or the paracentral area in lhe vicinity of lhe
vascular arcades, or it may involve the entire fundus. In
those patients with visible cysts in the macula, most show
a polycystic pattern of staining typical of cysloid macular
edema. In some, hoxvever, no staining, minimal staining,
or intermittent staining may occur (I'igure 5.42). Et is dif­
ficult to determine whether mosl of the fluorescein stain­
ing is derived from dye leaking from retinal capillaries or
from Lhe choriocapiHaris through abnormal RPE.53;|,5‘ia5ilL
Tluorescein angiography usually shows an increase in the
retinal circulation time and sharply outlined zones of
hyperfluorescence corresponding Lo the areas of atrophy
of lhe KPL. ]n some palients ihere may be a delay in lhe
development of choroidal hyperfluorescence in the area
of Rl3h atrophy, indicating s-ome atrophy of die under­
lying choriocapillaris. In others, the rapid development
of the diffuse background choroidal fluorescence suggests
the underlying choriocapil laris is intact. Autofluorescence
studies show decreased aulofluorescence corresponding
to lhe involved K Pt and periphery, and a ring of increased
autofluorescence in the macula suggesting increased meta­
bolic activity and lipofuscin accumulation in the macular
ЙРЕ cells (figure 5.3УС;, I ], K. and L).
Recurrent serous detachment of the pigment epithe­
lium and retina, identical to that occurring in idiopathic
central serous chorioretinopathy occurs as an infrequent
compEication in palients with retinitis pigmentosa/*1"503
Dr. Class has seen two such patients [figure 5.41A -C).
ihese patients should be distinguished from palients With
chronic idiopathic central serous chorioretinopathy, who
occasionally develop pigmentary changes that resemble
sector retinitis pigmentosa but that ,ue caused by long­
standing dependent peripheral zones of serous retinal
detachment (see i'igure 3.06 and 3.07).
liislopathologic examination of eyes of patients With
retinitis pigmentosa have shown degeneration of the reti­
nal receptor elements, depigmenlation of the Rl’Ei, migra­
tion of RPL cells into the overlying retina, particularly in
the perivascular areas, hyalinizalion and thickening of
the retinal vessel walls, diffuse atrophy of the whole ret­
ina, and gliosis {figure 5А\С-1).:^ 7^ Г:-12-Гм 'Ihese
changes are usually mosl prominent in the mid periph­
eral fundus. The RPE and choriocapil Laris are preserved
during the early course of these changes. Liter (he RPE
becomes atrophic and there may be partial obliteration
of the choriocapil laris. Degeneration in the pigment epi­
thelium and retina are probably of primary importance in
causing (he atrophy of (he choriocapil laris. 'l|f "lh As (he
disease spreads posteriorly there is gliosis of the optic disc
with extension of a fibrocellular glial membrane on Lo the
anterior surface of the retina [E'igure 5.41 H ).41'1 ' " in the
Continued
( t-L: Thin 22-уедг-old wom an whs a mumhtir of a family wilh
auLosamaF-dominanl retinitis pigmentosa. bhe had muderaleiy
severe changes ol roLinilin pigmentosa in bo’ li eyes i£il, w ilh
cycloid macular edema, dmionstratod on ihu angiogram (UK
Optical СопЁгегсе tomography confirmed lhe presence of
cysts in both macula (II and E2J. The inferior fundus showed
telangiectatic changes in [he Vessels w ilh lipid caudal ion and
retinal detachment !|-l... Laser was applied in severaS sessions
to both eyes; the rEghL eye responded wiLh resol ution Ы almost
all the lipid; however (he lelt eye continued Lo leak and Ihe
lipid exudation reached (he lovea Ln spite of m ulliple lasnr
Ireal men Is. Her vision remained at 20Л0Й on Lhe righL and
20.400 on the Ictr.
atrophic macular region, there is focal loss of the receptor
cells, the outer limiting membrane, followed by degenera­
tion of the RPE and attenuation of the underlying chorio-
capillaris (figure 5.4K1).
l.aige cystic spaces in the outer nuclear and outer plexi-
form layens and smaller cysts Lying in the inner nuclear
layer encircling lhe central area similar lo that seen in
aphakic cystold macular edema have been described in
one patient with retinitis p ig m e n to s a .In a study of the
macuLas of 41 patients with all genetic types of retinitis
pigmentosa, Slone et al. " found evidence of some Loss
of ganglion cells as well as the underlying receptor cells
(suggesting transsynaplic degeneration) but demonstraLed
that many eyes, particularly those with dominantly inher­
ited retinitis pigmentosa, retain many ganglion cells even
in lhe presence of marked loss of the underlying receptor
cells (I'igure 5.41]). Ultrastructural studies of the vitreous
of patients with retinitis pigmenlosa have revealed the
presence of RPE cells, uveal melanocyteSr retinal astrocytes..
lymphocytes, and macrophage-like cells....... ■ '
Kolb and Gouras on the basis of electron microscopic
studies suggested lhal the melanocytes collecting around
retina] blood vessel in retinitis pigmentosa may be uveal
m elan o cytes.' Et is difficult, however, to explain why
uveal melanocytes- which are poorly reactive cells, would
migrate into lhe relina and vitreous. It is more likely that
these are К PL celts that undergo a me! amo rp hosts thal
simulates uveal melanocytes. The prcdileclion for these
ftPL cells to accumulate around lhe retinal blood vessels
accounts for the bone corpuscular patterns of pigment
seen ophthalmoscopically. Newsome and Michels found
that the predominant vitreous cell type in retinitis pigmen­
tosa was the lymphocyte, most of which were T cells."’''1
They were unable lo determine whether the vitreous cells
played an aclive role in the pathogenesis of the retinitis
pigmentosa. The presence of Г cells in the vitreous may be
largely the result of breakdown in the blood-ocular barrier
ihat occurs in retinitis pigmentosa.'''
 Several subtypes of retinitis pigmentosa due to various
gene defects can show a variable appearance of the RPL
change. A type of relinilis pigmentosa With REE preserva-
ticm is seen in patients with Crumbs homo log I (C tfJi?)
от CHl/.VfB gene defect (See figure &.43G and H ] Some
patients show very little migration of pigmenL epilhe-
Lial cells* called retinitis pigmentosa sine pigmenti. Those
patients with autosomal-recessive retinitis pigmentosa
have earlier onset of symptoms Hind findings. Women,
who are X-linked curriers, can show a variable amount
of involvement. Sometimes involvement is sectoral and
occasionally it is extensive. Irregular lyonization of cells
es responsible for the varying degrees of symptoms in
feiitale carriers of X-linked recessive retiniLis pigmentosa.
Peri central retinitis pigmentosa patients have most of the
findings related to the in id peripheral fundus around the
arcades. Sectoral retinitis pigmentosa was first described in
1937. These patients generally have fine shiny crystals in
addition to the sectoral consideration of the photorecep­
tor loss. Several of the patients can progress from cone to
cone-rod degeneration.
Associated findings in typical retinitis pigmentosa include
congenital deafness ft|sher's syndrome) that may or may
not be associated with other evidence of centra! nervous sys­
tem abnormalities^2^ - 5™ vttlligp,50®'536-5^'554'557 and cal­
cific nod uIar d ruse n w ilh in the optic ne rve head 19 ^ 5isr'H
Calcified bodies on the optic nerve head in patients
wilh retinitis pigmenLosa have been attributed lo hyaline
bodies (drusen) by some4’ 5r5S* and lo astrocytic hamarto­
mas by others.1"'1 r'2'' The evidence in favor of the for­
mer is more convincing.
RetiniLis pigmentosa may be inherited in any one of the
three classic modes. There is a general tendency for earlier
and more severe involvement in those showing X-Jinked
recessive and autosoma I-recessive modes of inheri-
There are notable excep­
tions Lo the genera! rule that (he disease in families with
dominant inheritance is m ilder.""' Clients with X-]inked
disease are usually almost blind by the age of 30-^0 years*.
whereas many affected patients with autosomal-recessive
disease or no fautiLy history of disease retain central vision
until they are 45-60 years o !d .':" 11 An alteration in
sperm axoneme is present in patients with X-linked retini­
tis pigmentosa .Sfil-56J Almost 100% of the female carriers
of X-l inked retinitis pigmentosa cut be identified on the
basis of either or both fundus and ERG changes.',tJ '['he
fundus changes include tape to-! ike reflex in the macula.,
isolated regions of peripheral retina! degeneration, and
occasional]}' widespread retina! degeneration.
Some authors have subdivided patients with domi­
nantly Inherited retinitis pigmentosa into two primary
subgroups: one having diffuse pigmental ion. concentric
visual field loss, and no recordable TRC, the other with
regionalized pigmentation, sectoral held toss, and some
recordable ER & 5J5^ fi°j56*"Sb7 th e cumulative probabil­
ity of maintaining a visual acuily of 20/40 or belter over
each decade of life decreased rapidly in the former type
з. 4 E Re tinit is pig me ntosa and с enlra I se rous
ch ori orel ino pathyb
A —C : Recurrent episodes o f idiopathic central serous. reLi-
nopalihv associated with m ultiple serous detachments of
the retinal pi^rnt'nl ebtlheJjum ((№E: arrows, A and Cl
in bolb uyes occurred in this i 0-year-old w om an w ilh
relinilis p4gnrenUfca sine piemen 11 and а г exIinguishcHJ
elcjt/l rorel i nofttam.
Late onset retinitis pigmentosa,
D-F: Long-standing “late-onser retinitis piyrnenlosa
occurred in this ii6-ytar-old w om an w h o w;ls asymptomatic
uniii 3- months prioT to ibes*! piclures. Her family hittc]jv was
n e^ilive. Her visual acu ily was 20/25 riyjil eve and 20/Й0
left eye. b-Uu- had marked conctjhllfic conslriclion of the visual
fiefds bi laterally. Angiography revealed relative preservation
□f the Rh’E centrally and mild intraretinal staining in the cen ­
tral macular area of both eyes :b and Hi.
G - J: HisLopathologv oJ retinitis pigmentosa. .МасиГаг area
IG ' i show Mg yjflensive atrophy of Lhe receptor cull laytir that
is Ihimied Lo one cell I hackness i.arru^vH., and mild degen­
eration of I be K! hafc and slight attenualifitt of lhe chor:of:ap-
: laris. M id peripheral fundub 'H and li showing exlensive
j^li tjsi-s and atrophy of the lelina, inlrarelinal migralion ol' K F t
around sclerosed retinal blood vessels, atrophy of Lhe KFE
and chcmocapiHarih 11own: arrow I, and celiular epirelinal
membrane ■;upper ^rrow, IJ. H ig h -power v ie w showing ^ilre-
uus cell filled with m-elanin pigmenl I).
iA-t.. fcfim
and remained above 90% through the fifth decade in the
latter type. Patienls with dominant disease can retain cen­
tral vision beyond the age of 60 years.
A number of distinct mutations in lhe rhodopsin gene
have been identified in different families with autosomal-
dom inant retinitis pigm entosa.'" и 4.5м,5*г-я?а l he re is
evidence lhal some cases of dominant retiniLis pigmentosa
are the result of mutations in the retina! degeneration slow
{HDi') gene on chromosome 6. *Ts Rosenfeld et al. reported
a rhodopsin gene defect in one family wilh autosomal-
recessive retinitis p ig m e n to s a .DisLinct mutations have
not been identified in patienls wilh X-l inked retinitis pig-
menLosa. ^ 1'^ (acobson et al. found discernible differ­
ences in the pattern of retinal dysfunction in patienls with
different rhodopsin mutations.1'1"
A natural course study of retinitis pigmentosa иnasso­
ciated wilh systemic disease showed significant decline of
full-fieId LRt; amplitudes over a 3-year period in 77% of
patients with delectable levels al baseline.' u Patients lost
an average of 16-1 £.5% of remaining £RG amplitudes per
year and 4.6% of remaining visual field per year.
Most patients with relinilis pigmentosa have myopia
except for those with early-onset autosomal-dominant ret­
initis pigmentosa with nanophlhalmos, Ijber's congen­
ital amaurosis, and preserved para-arterial RPK. ( figure
5.43C and H ).'1,8*1
Autoimmune responses have been detected in many
degenerative ocular diseases, including relinilis pigmen-
tosar but their role in the pathogenesis of retinitis pigmen­
tosa is unknown .’’11'"'''"'1
 Ib e iE is no proven effective treatment to slow the loss
of visual function in patients wilh retinitis pigmentosa. A
randomized trial of vitamin A {1 5000 ELl/day) and vita­
min i. (400 lU/'day) supplementation for retin Elis pigmen­
tosa showed a beneficial effect of vitaitiin A in regard lo
jfihibiting decline of JiliCI amplitudes* but it failed lo dem­
onstrate any benefit in slowing the course of toss of visual
field 'Ehe results of the trial suggest an adverse effect
of vitamin H on the course of retinitis pigmentosa. Lfse of
oral acelazolamide and melhazolamide and topical doraol-
amide for the treatment of chronic cystoid macular edema
in patients with retinitis pigmentosa has been beneficial in
some cases.,L' 3n some cases acuity improves without
demonstrable improvement in the degree of angiographic
fluorescein Leakage, '['he mectianism seems to be via stimu­
lation of the pump function of the KE4i. Results of a scat­
ter pattern of grid laser treatment for cystoid macular edema
in a small series of patients with retinitis pigmentosa are
unimpressive, and risks of this treatment in patients with
only a limited peripheral field are high.0^' there is some
hope for the therapeutic # u e of Iratisplantation of retinal
tissues and gene therapy for retinitis pigmentosa and mac­
ular degenerative disorders. I'ranssderal transplantation
of RE31: into the subrelinal space of animals has retarded
photoreceptor degeneration in the vicinity of the trans-
plaEtt. itansfer of correctixre genes into the subrelinal space
by the use of viral vectors is another possible strategy for
therapy. Tissue growth factors appear to inhibit or slow
the rale of hereditary retinal degeneration in anim als.^
AlLhough studies of patients wilh diabetes and relinitis
pigmentosa have shown a protective effect of the latter in
regard lo the development of diabetic proliferative retinopa­
thy, optic disc and relinal neovascularization does occasion­
ally occur ■ ' ' ' When relinal neovascularization occurs in
diabetics wilh relinitis pigmentosa, it usually develops in
the periphery al the junction of perfused and non perfused
relina. Ilicrc ;> EH'gjUve associ.ition ■■:' rbegmatogenoLis
retinal detachment in patients wilh retinitis pigmentosa. "0"
Recent studies With implantable chips thal function as reti­
nal receptors are in progress. Elapid and extensive expanse in
genotyping and genetherapy processes is likely Lo result in
novel therapeutic approaches for these patients in the near
future.
Lleclrorelinography dark-adaptation studies, and auto­
mated light- and dark-adapted perimetry are useful in the
diagnosis, classification, and follow-up of patients with
■ ЧГ - i №М
ret milts pigtnenLosa.
Usher Syndrome
Usher syndrome is an autosoma I-recessive disorder of
deafnessr often congenital, combined wilh features typi­
cal of retinitis pigmentosa []:igure 5.42С1 to |). Cystic or
atrophic macular changes are seen earlier in patients with
Usher's than typical retinitis pigmentosar and are more
prevalent in type E (61% ) than type El (32%J, most likely
due to the more severe and earlier involvemeEit in (he
ЬЛ2 Relinitis pigmentosa: response of cystoid
macular edema (CME} to acetazolamide.
A —F: Tinii ? 5-yea г-oEd African Am erican m ale had a. best-
corrticLt'd visual acuity o f 20/80 a r d 2Q/7D. In addition Id
the peripheral plgmenLary retinopathy,. a large central cyst
suncmnded by a few зтаГ1 Lysis- w ere presen L in both macu-
Eas (A and Bj. O ptical coherence tomography docum ented
the cystoid m acular edema in e a d j eve tC and D^. He was
treated with oral aoelazolam ide 250 mg (hree times a day,
which he toleraled well. EiLjhI weeks Liter bfs visjorc had
improved to 20/40 and 21V.10 nes-pectivelvr ihe cysts had
decreased significantly in both eyes (E and Fj. Acetazolam ide
was conlinued a I I he same dose fur 2 more months and
slowly lapered (ail over llie nest ? month s. Tht! CM b recurred
once he cam e off the aoefaj!oraniide and he w as ккр1 or>
m aintenance dose of il from I hen onwards. The cys-L in the
right eye persisted, but the left eye remained resolved.
Usher's syndrome.
G —|: A bS-year-old older brother has been follow ed for
Usher's syndrome for more lhan 20 уел гг. HLs visuaE acuity
has remained at h a n d motions for Lhe p a s l 20 years. Holh
eyrre h a d estunsive relinal a t r o p h y , including l h e macula ilh
bone corpuscles retinal piemen I epi I helium :F iP f n_jjura­
tion '.CJ and H:-. His b4-year-old younger brother h a d 20/400
vision t n each eye. The o p l i c nerves w ere p a l e bilaterally;
vessels were narrowed w ilh exLensive pigment migration ir>
еле I: eye It and |J. The m acula had some preservation of KPb
L h a t a c c u u n L E h d for t h e 2fV400 v i s i o n .
former.'"'' ']"hough von Craefe first described the condition
in Charles U slier, a British ophthalmologist, noticed
the hereditary nature of the disorder.
Usher syndrome can be divided into three major
groups, lhe two most fret]Lient forms are types ] and 19. Iti
type I. there is profound congenital sensorineural deafness
resulting in prelingual deafness and speech impairment.
Vestibular symptoms and childbood-onsel retinopathy
accompany (he deafness. 'IVpe II is characterized by par­
tial or profound, but non progressive, deafness, absence of
vestibular symptoms and milder, laler-onse! retinopalhy.
The least common is type III, in which there is progressive
deafness starting late in the second lo fourth decade of life
onset of retinopathy in adult life, and hypermetropic astig-
matism.:'u' lype LIE resembles type El except for progressive
worse]i ing of hearing.
Approximately 3-6% of persons have profound pre-
iingual deafness of type 3 Usher syndrome, lype il Usher
is more common and accounts for about two-thirds of
patlenls. 'Eype Ell constilutes less lhan 20%. 'lhe tR ti is
nondelectable in alt groups early on in life Occasionally
a Lype El Usher can have cerebellar atrophy resulting in
ataxia. Type Ш has been associated with psychotic symp­
toms and magnetic resonance imaging (MRE) changes
associated with this*fiQ4,6flS rIhe disorder is genetically and
clinically heterogeneous and at least nine genetic loci have
been identified. Usher type E has six different gene loci,
mapping Lo Mq32. H q l3 , 11p 15, ]0q, 2lq2l and chro­
mosome 10. Usher type 11 has been mapped to 1ц41, Зр..
and 5q. and others have been postulated.1"
! лггпп— шщйфр^у1gjjfpj tjjjj'
 Cochlear implants can be placed in profoundly deaf
children and lhis has helped their speech. Usher syndrome
can be mistaken for rLibella retinopalhy due lo lhe deaf­
ness and pigmentary changes. However, an ERG w ill be
useful in confirming lhe diagnosis of Usher's. Other syn­
dromes lhal can be associated with deafness and pigmen­
tary retinopathy include infantile Refsum disease, adult
Refsum disease, (iocayne syndrome. tiardet-ftiedl syn­
drome, Alstrom disease, Flynn^-Aird syndrome, Friedreich's
ataxia, and Kearns-Sayre syndrome.
Typical Pigmentary Retinal Dystrophy
with Coats' Syndrome
Some patients with typical sporadic or familial reti­
nitis pigmentosa, usually during adulthood, may
develop yellowish subnelinal exudation derived pri­
marily from lhe peripheral retinal vessels and present
wilh a Coats' syndrome picture {figure 5.40C-E-' and
G-L).Jfl7,j1H,'l ^ijMfl,slu,,5Cl?,Sl1,5li'-bl,7"SQ* Tbe exudative detach­
ment may be confined lo the peripheral fundus, or it may
be massive and extend inlo lhe posterior pole. Total reti­
nal detachment may occasionally occur.6'11' J-'ocal areas of
irregular telangiectatic dilation of the retinal blood ves­
sels, and occasionally angiomatous proliferation of reti­
nal capillaries, occur usually in Lhe peripheral fundus on
a background of the typical finding of retinitis pigmen­
tosa. Fluorescein angiography may show widespread evi­
dence of capillary leakage in lhe retina in areas outside
as well as within the area of exudative retinal detach­
ment. Cystoid macular edema is usually presenL. the
exudation may be self-limited (Figure 5.40E and K), or it
may be progressive anti result iti extensive loss of vision.
Ihese patients require pholocoagulation and cryotherapy
to control the exudation [Rgure 5 40]-l.J. lhis exudative
response may also be the cause of massive segmental reti­
nal gliosis in these palients.'1'1 IlisLopathologic findings
in one case revealed evidence of communication of cho­
roidal blood vessels ivilh tbe oVEriying exudative retinal
mass.1'1-1 h is uncertain whether this communication is of
primary importance in causing relinal exudation or occurs
only secondarily after a long-standing exudative retinal
detachment.
Angiographic evidence of retinal vascular leakage,
either confined to lhe macular area or involving the
entire fundus, has been frequently observed in retinitis
pigmentosa/^-1, as well as a variety of olher atypical
tapeloretinnil dystrophies, cone dystrophy, rod-cone dys­
trophy. Slargandl's macular dystrophy, and familial exuda-
ifve vilreoreLinopalhy. it is probable that massive yellowish
exudative deLachment in patients with retinitis pigmentosa
represents an unusually severe alteration in the relinal vas­
cular permeability lhat can probably occur in any of the
inheritance patterns of retinitis pigmentosa. ЧЪе frequency
of bilateralilv, adult onset, and absence of sex predileclion
suggest strongly that this exudative response in patients
wilh relinitis pigmentosa is unrelated lo congenital retinal
j . 4 3 Retinitis pigmentosa with unusual peripheral
relinal changes.
Д -С : lietinilis punctata albescens in a 12 -y p flk l Id man w ilh
nyctaEopia, progressive loss of peripheral vision, and m ul­
tiple, discrete, round, white flecks at Ihe level Ы the relinal
pigment Epilhelium I HP E- in the peri centra I чэ-геа i'A l These
flecks w ere more numerous and smaller in the mid periph­
eral area where there we/e m ore advanced alnophic changes
in the RPfc and retina. Note lhe narrowing ol lhe relinal ves­
sels 16 . Angiography revealed widespread dupi^menlalion of
ihe K P t lhat was more marked peripherally Ю .
D -F: Peculiar perrvatt Lrlar and ^eogranhii (jttfctribiiEtin of
subreHnal w hile lesions i> - H i in a wom an with nyctalopia
and evidence of a lapetorelinaE degeneral ion.
G and H: Periarlerial sparing of Lhe pLgmenL epithelium and
an O^uchj-l i ke metaEEic refte> in lh e periphery o f a healthy
8-year-old hoy w ilh nyctalopia, on;-el of progressive visual
loss al age 5 years, and an eHlingurshed eleclrofetinogram.
His visuaT acu ily was 2 0(i bilaterally. 1hero was no nys­
tagmus. lie had Ihree norm л I sib lin g . There was n-o histciry
of c(Hisa n^uinity.
i—l i 1hree-dimensional ]ace3il;e network ^>1" white relinal
capillaries l|-l.i in a 34-year-old wom an with л Iifelony his­
tory o f nyctalopia, severe loss of peripheral visual field, and
,m extinguished eleclroretinogTan^. She had a sisler w ilh
Lhe same ocular disorder. Her visuaJ acuiLy was 2(1/60 in
the eye and 20''5D letl eye. Her eleclrorelinogram wag
eKlingnished bilalerally.
lelangiectasia, the most frequent cause of Goats' syn­
drome. Dr. Gass has observed it developing in one patient
during follow-up for a unilateral localised area of pseudo-
retinilis pigmentosa change caused by trauma. Mutations
in the Cfi£! J gene have been found in Ь5Уо of palients with
Goals'-type retinilis pigmentosa, lhe condition has been
seen in palients as young as 4 years and in patients with
Usher syndrome type I1.Q 11 fil"
A T Y P IC A L F O R M S O F R E T IN IT IS
P IG M E N T O S A _________________________
"Atypical pigmentary relinal dystrophy” is a term applied
lo relinal dystrophies lhal are closely related Lo typical reti­
nitis pigmentosa and in some cases are incomplete forms
of the disease.
Leigh Syndrome {NARP Syndrome)
Leigh syndrome is a hereditary neurodegenerative disorder
of infancy or childhood, and is characterised by develop­
mental delay, psycho mo tor regression, signs of brainstem
dysfunction, lactic acidosis, and symmetrical necrotizing
lesions in the basal ganglia on the brainslem ]he clinical
course is variable wiLb mosl cases of a poor outcome wilh
progressive neurological deterioration Eeading lo death
Within months or years, 'lhe definitive diagnosis depends
on MR] changes, described as hyperinlense lesions of the
put amen and the brainstem.
 №AHF syndrome is typically caused by defects of the
mitochondrial enzymes Including pyruvate dehydroge­
nase and complexes 1, 2, and 4 of the respiratory chain.
In most cases, the deficiencies are due Lo mutations in
the nuclear genes ,ind coding subunits of the completes
PL>HAlr and M )J ЕЛ, proteins implicated with assembly of
complexes such as SURJ-'l and LRPPRC. In addition, mito­
chondrial 1DNA mutations are important causes of tiig h
syndrome. А ГЗЗЭЗС! mitochondrial DMA inula Lion is a
cause of Ijeigh syndrome."11-015
The clinical picLure is variable, and some patients have
a milder phenoLype. Iliese patients who do not fulfill all
the criteria Гог l^igb syndrome, are classified as ].eigb-like
syndrome, and they have a better prognosis but a lower
biochemical and molecular diagnostic yield than patients
with E.eigh syndrome. The phenotypic variation in lhe
mitochondrial ЕЖ А mutation is due Lo heteroplasmy or
variable affection of the mitochondria! E>NA mulattons.^1'
Jhe A-f'iLATJ45 gene encoding lo subunit 6 of the adenosine
triphosphate symhase complex S is the commonest DNA
gene mutation seen in cases wiLh NAKP. Ibe J^ y^ j gene
muLation is the commonest [nutation seen.'014
Some patients are known to improve significandy after
lfi-1 a yens of age.0,1' 'Itiis may be due lo the decrease in Lhe
mutational load wilh age that has been observed in some
patients. rlhe ocular changes that have been seen in these
patients can be variable, bull's-eye maculopathy has been dis­
covered in an infant with Ijeigb's disease noted al the age of
ft months. In niddilion, lhe relinal arterioles are diffusely nar­
rowed wilh consecutive pallor of the optic disc,|иа consisLent
with diffuse loss of photoreceptors. Optic atrophy, nystag­
mus, strabismus, ophthalmoplegia along with developmen­
tal delay, hypotonia, seizures*, and psychomotor regressions
are all features of Leigh's disease. I.eigh's disease should be
considered in Lhe differential diagnosis of neurologjcally
impaired infants presenting with a bull's-eye maculopathy.
Retinitis Pigmentosa Sine Pigmenti
Patients with otherwise typical retinitis pigmentosa may
show minimal or no evidence of pigmenl migration into
the retina (Ttgure lleariman and associ­
ates1,-v have presented evidence to suggest that the absence
of pigment migration represents an initial stage of typical
retiniLis pigmentosa and is manifested by shorLer dura-
Lion of symptoms, less severe nighL blindness, and less
impairment of the electroretinographic b-wave. Eiecause
some patients may initially be seen with visual loss sec­
ond ary to cystoid macular edema or with field defects
simulating arcuate scotomala. these patients may be mis­
diagnosed as having a neurologic disease or glaucoma.
The ophthalmoscopic findings of waxy pallor of the opiic
di&Cr a glistening reflex secondary Lo epirelinal membrane
change, a greenish or gray tapelo-like reflex from the
altered RPE, and slight narrowing of the retinal arterioles
should alert the clinician to inquire concerning symp­
toms of night blind ness and to obtain elec trap bysio logic
studies, Kluorescein angiography is helpful in detecting
j.44 Bothnia dystrophy.
A: A 1.‘i -year-old male with ni^ht blindness ^-ince parly (.hild-
haod, with 20/20 vision in berth eyes. Visual fields were lull
bilaberamG rod responses w e n 1 undeLectable, minted rod and
cone response's were poor, and lhe CORife reSfHJnatJ Was sub­
normal. Left eye shows uni form w hite dots resembling flecks
o f fundus albrpunclatus (A). The severely diminished s c d -
topiE find phc>tc.hpiс amplitudes di fteren Ii ale il 1тот Ktfidus
albipunclatus.
В and C: Hi is 16-yea r-okl female w ilh a visual acuity of
2 0 3 0 both eyes bad a relative rinj^ scotonii5 and suffered
nj^ht blindness мпсе смг1у childhood. Her rod and mixed
rod and cony responses w ere undetectable and the to n e
Responses w ere subnormal. The fundus shows aiffuse
^lisLenin^ pun cl и ate white dols interspersed w ilh hyperpi^-
mented doLs (B and Cl.
D ап-d Ibis 26-year-old fem ale With history of nighl blind­
ness since early childhood and progressive loss o! central
vision had a visual acuity of 2&2Q0 botfi eyes. bhows ai:
older phenoLype Ы KoLhnia rivslrophy with fliffclsely allered
pigmentation of her fundus i'15) and peripberaI islands of
^eojjraphic atrophy Tesemblin-i^ ^yrale atrophy (Ё). Her visual
fields showed relative central and paraccnLral scfrtomas. The
rod and mixed responses were undetectable and the cone
responses w ere low.
f and G : A 3C)-yoar-<jld jwOman w ilh distinct pu n d alij white
dots in lhe macula and diffusely mottled pigment eprtheEium
OLMside lhe m acula [F a ltd Cj'. Her vision was £L¥1DD ri I
eye and count finders left eye. ih e had hi la Lera I Central sco­
tomas and undmectnbrE rod and cone геуропкен.
H: A 42-year-old female with 2-0/200 vision in both eyes,
undeleclable rcjd and cone eiedrOrelinOgrajns w ilh white
dols all ovei the fundus and toveal atrophy (H,!1-
IvJ-ULirl.-L-jyC.-I Ur. 01,1 ^Lincl^run ,ind l>r. iVLlflr !1l|--.1L'(il
zones of depigmenbitiou of the ЙРЁ not readily apparent
ophthalmoscopically. ] Eislopathologically, the changes
are si mil ar but less severe than those in typical retiniLis
pigmentosa. I'll ere is evidence of pigment migration into
the retina but in amounts insufficient to be detected
op h(hal moscopica I Ly.
Preserved Para-arterial RPE in Retinitis
Pigmentosa
Jfecken lively reported five patients with relinilis pigmen­
tosa. probable autosomal-recessive inheritance, hyper-
melropia, and preservation of the R Pt beneath the retinal
arteries in areas of otherwise severe pigment epilhelial and
retinal aLrophy [Figure S.43С and Mutations
in the (GltBl gene have been reported in a variely of
autosomal-recessive retinal dystrophies, including retinitis
pigmentosa wilh preserved para-arteriolar EiE^,1'-22 relinilis
pigmentosa with Coals'-Jike exudative vasculopatby, early-
onsel RPK wilh preserved para-arterial RPE (PPR PE), and
JjebeKs congenital amaurosis.f,J^IL appears that loss of func­
tion of members of the CRB/Cfijfi complex in Drowpitila and
vertebrate retina results in typical architectural disorganisa­
tion and light-induced degeneration. The alterations occur
at the RPG photoreceptor level and also at the Muller cells.
Retinitis Punctata Albescens (RPA)
RPA is mostly an autosomal-recessive conditit)n (rarely
dominant}*^1 with multiple small gray or while dols that
resemble lhe flecks of fundus albipunctatus. Confinement
of lhe flecks lo the region iust outside the macula (not
reaching the periphery), progressive night blindness, nar­
rowing of relinal vessels, loss of peripheral field, and
appearance of pigment spicules differentiate it from
fundus albipunctatus {figure 5_43A-C)j467'3S3'625-*2''
Intermediate forms of these disorders exist.
RPA is mostly associated wilh mutations in
НЛД^Зг'1*410^"^1 and occasionally in KDS, and
ЙОН:5 g e n e s . I here is a wide genetic heterogene­
ity amongst a reasonable phenotypic uniformity in ihis
condition. Various mutations in lhe R LB Pl gene have
heen found, and in some cases none of the known muta­
tions is positive.1 , ilolhnia dystrophy and Nl^RCD closely
rtoembJe RPA in many features and the gene affected is
however the mulattoiis are different j&Om
those known for RPA.
The differential diagnosis includes basal laEninar
drusen, fundus llavimaculaLus., isbetalipoproteinemia..
oxalosis, cyslinosis, talc emboli, Alporl's syndrome, can-
thaxanthine retinopathy, and fundus xerophlhaimicus.
Other types of leeks and peculiar color changes of the
peripheral retina occasionally occur in patients with reLini-
tis pigmentosa (figure 5.43!>-].).
Bothnia Dystrophy
Jhe onset, is in early childhood wilh symptoms of night
blindness when the retina appears normal. Hunctale while
dots of RPA appear in leenage and young adults (Figure
5.44A). Macular pigment deposits (E'igure 5.4 4B, Cj fol­
lowed by macular atrophic changes occur next (Figure
5.44D. il). This is followed by paracenlral and mid
peripheral round chorioretinal atrophic lesions resembling
gyrate atrophy [E:igure 5.44E:) and narrowing of retinal ves­
sels. Widespread pigment epithelial migration in the form
of bone spicules occurs occasionally. Visual acuity progres­
sively declines wilh age, leading to legal blindness by (he
fourth decade of life. I hose whose vision never develops
beyond lU/iiU show nystagmus. Premature cataract has nol
been a feature. Muorescein angiography shmvs mottled
transmission defects from Rl]H atrophy.< :"w'
Visual fields are normal in young patients; gradu­
ally increasing central scotomas develop in the teens
or in young adults, eventually Eeaving only peripheral
islands of visual field. Color vision is affected early and
worsens with age. L>ark adaptation studies show abnor­
malities of both rod and cone function that progressively
worsen, Eilectrorelinography shows decreased amplitudes
i,-l> Newfoundland rod-cone degeneration (NFRCD).
A iind B: Ibis 47-v-rw-ukl m-iika w js inito|igalEid for hypor-
rt?il-c!x.i.1 nnd <ihnomi;il ^iiC iti 1993 In 2000. u^Lil dlj^hir^ntp
Worsened And ,i reLinaf degeneration was п-oted. LerciEreJlar
mid cerebral atrophy was foLfnd on maj;i>Eflic roat]minte
ima^in^ in 2001 r and by 2007. lh e spabLrdty Lonfined him
Lo л wheol thisi r. Me w^s found to h,ivu puricLaLE* whiltf
ail over lhe Гиги:Jus \early slag,e) with some patches c l relinal
pigment epithelium/cburiDcapilLdry atrophy (A and tJl. O n e
sister had similar history and findings Lind two olEit'r siblings
find faiirenis Were и п .;Mec I ud. His jod etectrpbetinogram
f 1лL Sind tone? responses were? diminished.
and increased i пэр licit times for rod and rod-cone func­
tion early, and progressive cone dysfunction laler on.
Individuals heterozygous for the mutation show near­
normal EiRG amplitudes and implicit limes. E:OC is sub­
normal in all patients.:,4°-,b,u
It is a unique auLosomal-recessive rod-cone retinal dys­
trophy first described in the Etothnia Occidental is region of
Vasterbotten county of non hern Sweden, with a high prev­
alence of I per 4500 population, lhe disorder is caused
by a mutation in the R LB Pl gene mapped to chromosome
I5q2ft, encoding the human cellular retinaldehyde-bind-
ing protein (CElAE.iiPj. Patients affected by Bothnia dystro­
phy are homo^gous for a C-lo-T transition in exon 7 of
(he Ri.tfPJ gene, leading to an arginine lo tryptophan sub­
stitution al position 234 of the protein (EiI34W ). C RA lBP
is located in the RP!\, Muller cells, ciliaiy body pigment
epithelium, outer epithelium of the iris, cornea, the optic
nerve, and pineal gland. En the КГЕi it functions as the car­
rier protein for endogenous retinoids such as 11-ci'j-retinol
involved in the visual cycle. Defect in the gene leads
lo defective binding of 11-сез relinaldehyde, thus prevent­
ing its regeneration, and subsequently loss of rod func-
lion.:' "" 3le et a I. found R23 4W displays fivefold increased
resislance to light-i nduced photo isomerization relative lo
wild-type GRAE.liP, caused by unanticipated domino-like
structural rearrangements causing Bothnia-type retinal
dystrophy by (he impaired release of 114'i.c-retin,d from
R234W'':-
Other mutations in the gene have been
described: R]50Q in exon 5 in three patients from India
and in patients from Saudi Arabia, three additional muta­
tions in a small family of Eiuropean ancestry and two
splice junction mutations, one of which causes .NI:RCL}.
Most of these patients present with white flecks, peripheral
degenerative changes, and maculopathy and resemble the
phenolype of Bothnia dyslnuphyr except NI-'RCl), which
has an earlier onset and more rapid progression and so far
has nol developed the macular areolar atrophy."36j6J 1tj4]
Newfoundland Rod-Core Dystrophy
Symptoms begin in infancy with night blindness, followed
by progressive loss of periphery central, and color visit)n
in childhood, resuUing in severe visuaE Iон by the second
to fourth decade of life. Several while dols similar to fun­
dus punctata albescens/fund us albipunclatus and Bothnia
dyslruphy may be seen in lhe posterior pole and midpe­
riphery in ьогае patients, hi contrail to Bothnia dystrophy,
where macular involvemenl occurs early, the macula in
N R iC l) is normal or exhibits a 'beaten-bronze* atrophy. A
perimacuSar ring of white stippling simitar to that in RPA
is observed in young patients, and a scallop-bordered geo­
graphic atrophy of the mid peripheral ItPE develops over
time {Figure 5.45A and 'Lliis is similar in appear­
ance to early gyrate atrophy, choroideremia, and Bothnia
dystrophy; however, plasma ornithine levels are normal.
Clalaracls have not been documented, myopia is not seen
consistently, and glaucoma has nol been identified. Roue
spicule pigmentation is nol seen, optic discs are either nor­
mal or show trace pallor until late slage, and only mild
attenuation of retina! vessels is seen in advanced disease
[Figure 5 .4 5 ф к),^ *
The EiRC rod responses are selectively reduced early, and
the EftG rod and cone responses are both extinguished in
advanced disease, 'lhe early visual field defect is a ring sco-
Loma close to fixation rather than in lhe mid peripheral
field seen in dassic relinitis pigmentosa (l:igure 5.45L).
CenlraE visual acuity may be as good as 20/20-20/60,
although the ceuira! field may be less than 5q. lhe rate at
which the ring scoLoma widens and becomes a complete
centraE scotoma is an indicator of the rate of progression
IA j Continued
C—L: This pa Lien L w ilh NFK.CD had confluent peripheral and
in id pufiphufril lacunar atrophy ir> bodi eyes i m idsla^e, C
end Angiogram showing ^moth-eaten" retinal pigjneni
epithelium jn Lhe mat ul;i Lind loss Ы cJioriocapill aris in Lhe
areas ol" lacuna г atrophy, Com posite images show Lhe enteriL
лг>Н dis^ribulion of the atrophy in lhe midperi pinery in holh
eyes ( ( j — Five yea re Iл Lew, Lhe Eacunar atrophy appears sta­
ble without pnojireshion inLo the m acula in bulh eyes [] and
Kj. Visual Field defccLs correspond Iо the lacunar atrophy
with ring scotomas early in the disease, but o nly remaining
temporal field w hen the di-sease is ad vances ana elctends lo
Lhe m acula (Li.
К Ч 'И Г Ь л у ( j f I J r J . t n i L - ! W h f c 'I . l N
of the disease. Color vision defects are initially mild red/
green with or wilhoul blue/yelloxv defects, but this pro­
gresses rapidly Lo eventual loss of color perception. I here
are however exceptions where palients in iheir 30s or 4Lls
have only mild to moderate color vision defeels.6ia
Llie area in Newfoundland in which lhe majority
of affected paLients reside is wilh in a Ю-mile (IG-km)
radius. Most inhabitant here migrated from southwest­
ern England in the mid Ifclh century, and tbe popula­
tion has remained fairly isolated till recently. A single
common ancestor has not been identified. Two Н1.БГ1
splice junction mutations are responsible for WFRCD,
whereas missense mutations of NLHPJ are responsible
for UFA, Bothnia dvstrophy, and autosomal-recessive
Bietti's Crystalline Tapetoretinal
Dystrophy
Puli ems xviib BLetlf's crystalline tapetoretinal dystrophy,
usually males, are Liiittally seen In middle age because of
slowly progressive loss of vision frequency unassociated
with nyctamfea.^J-&53 ]n lhe early slaves of lhe disease
fundoscopic examination repeals a striking fundoscopic
picture characterised by the presence of glittering crystals
scattered ihroughout the posterior fundus (Ngure 5.4 A,
I>. i l. and Ij. lhese are located in alt layers of the retina
and can be con firmed on pC T .65^ 657
Ihere are oflen multiple areas of geographic atrophy of
the RPE: in the posterior fundus [higures 5.46 and 5.47).
Ault)fluorescence imaging shows decreased autofluores­
cence со [responding to lhe areas of RFE loss, punclale
increased auto fluorescence corresponding lo pigment dots.,
possibly RE’t hyperplasia, and very little hyperautofluores­
cence of the crystals.10’ lhe crystals are less apparent in the
areas of pigmenl epithelial atrophy. lhe optic disc and reti­
nal vessels are typically normal. Jhere may or may not be
marginal crystal line dystrophy of the cornea characterized
hy lhe presence of sparkling yellow or white, round, polyg­
onal or needle Iike crystals located in lhe anterior stroma
of the peril imbal regjon.'e<u'W 6--&5Dj653 These crystals may
become more prominent lale in ihe disease^, and biopsy
of the I imbal conjunctiva and cornea has shown these ays-
Lills to be complex lipid inclusions within fibroblasts.1, H
The electmrelinographic and electro-oculographic fitidings
are usually subnormal. hluorescein angiography reveals
atrophy of the ehoriocapiHaris in the zones of pigmenl epi­
thelial alropby. 'Ihe&e zones progressively enlarge, become
confluent, and extend into the periphery of the fundus, lh e
rate of progression and severity of the disease are variable.
I'tgure S.4G (H-L) illustrates a black woman who had rapid
progression of the disease. Most cases have been reported
Ш patienls of Italian or oriental extraction, in particular
Chinese and Japan^ fib,'6W -lSfi3
B le ttri crystalline tapetoretinal dystrophy.
A—D : Atypical pijgfneritiry njlinal dystrophy asiiod^led ^vilh
widespfead subretinal crystalline deposits in a 54-year-old
man of Italian descent w tio had recently noted paracen­
tral Hi'ulomas in both eyfis* His visual acuiby was. normal.
Note lhe relative bafjfefty of u v s la llin e ВД ЁЫ нт in those
areas of geographic atrophy of the relinal pigmenl epithe­
lium (RFE) (A and B). Visual field defects corresponded
with the areas oE R PE Q EpiKltenlation. The corneas and
conjunclivae were normal. His ^leCbi>cicit)p® 3 rn was nor­
mal. Elccrnornjlirm^raphy showed subnormal rod and cone
responses in bdth eyes. !Hrs pas1 medical hrShJty was unre­
markable. He had normal levels of serum ornithine and
urine oxalates. There was no fam ily history o i consanguinity
or visual loss.
E and G: This 34-ycar-old Lebanese man noted slow Itfss of
cunlral vision for several w ars. His family history was r>ej“-
alive. H it visual acuiLy was; J0/70 righl eye and 20/50 lefl
eye. He had many retinal crystals in lhe posterior lundi IE:
anti sublie crystals in the corneas. There was evidence of
early geographic atrophy of the -KPE m the righl eye <E-GK
Note evid w ice ol non-perfusion oi the chariocaprilaris para-
ccnlrally (arrows) and d e ti grnehtat ion o f lhe K^E ihroufjhoul
lhe macula iJ- and C j. An electron^ no^ram revealed mild
decrease in cone amplitudes.
H-L: This 15-year-old female had many variably sized crys­
talline d e p o sit throughout lhe poslequalbrial fundi IH and
I). Three and one-half years later, ^he had severe visual loss,
alrophy of Lhe piymen! epi I helium. loss of lhe crystalline
material, and sheathing of lh e choroidal vessels (|). Note the
extensive lass of lhe choriocapillaris evident in the angio­
grams (K and U .
 The hereditary pattern is autosomal-recessive and the
causative gene is CYi*4V2, which belongs lo the cylo­
ch rome V450 hemilhiolate prole in superfamily атщ is
responsible for oxidizing various substrates in Lbe meta­
bolic pathway, Several mutations in ihe CYF4V2 gene
have been described.1"^"’"" Cultured cells and peripheral
lymphocytes from patients with Uietti's crystalline tape-
Loretina! dystrophy are found to have abnormally high
triglycerides iand cholesterol storage, and reduced metabo­
lism of labeled fally acid precursors, suggesting that liic:tli s
crystalline dystrophy may result from abnormality of lipid
metabolism/'"'"^ ‘^"'ЧЬе nature of the crystals within die
retina is unknown, bul is presumed Lo be similar nr related
to the inclusions in ihe corneal and dermal fibroblasts and
peripheral blood lymphocytes.
j.47 E^etH's crystal line dystrophy;
A—D: This 47-year-old woman of German descent tom-
piained of nighl blindnoss lor mcnfe than 10 years. Ни visual
acuily was 20,40 on Гht.1ri^hl and 20/100 < j i >ihe lefl. Diffuse
яtrophy ul the reti nail pigment epithelium < Kl-1Ьi ard uhorio-
capillaiis н'ли seen in l.he posterior pole with shiny yellow
white crystals all over in iioth eves. Fluorescein angiography
showed diffuse dioriofolinal abtJphy wilh pakh pruscfv-iLtiur*
□f RРЫand chor io.api Ilari s Iti-D'i.
E—I: A 50-yeac-old Hispanic wom an w ilh com plainls of pho­
tophobia and nycatalopia had a visual declin e lo 20,40 and
20/100. C ulo r vision was diminished [cj2/1J on lhe righl and
0/12 on [ho lerl by Ishihara tenting. Kolh eyes showed cenlral
FiF’L'choriocapillafy atrophy w ilh shiny (.ryslals ihroughoul
Lhe fundus (E and Fk ChorLocapiflary and R F E loss were seen
cm angiography i.G-l).
l u l g r f C e a y flf. Dr. Iir i.:ii M < t^ u
.ItyfJj'oiJ Porm i i’f Pigm etitQSfl 349
Leber's Amaurosis (Infantile Tapetoretinal
Dystrophy, Retinal Neuroepithelial
Dysgenesis)
Leber used the раше Congenital amaurosis" lo describe
an aulosomal-recessively in he riled disorder character­
ized by blindness or very low vision aL birth, failure to
(is, nystagmus, sluggish pupillary reaction, occasional
photophobia, a positive oculodigital sign, and hyperopia
in patients who later developed evidence of retinitis
jMgpKniasa.a5fi,sa3jS66^fc&aPatteiit3 with ljeber's amauro­
sis are usually hyperopic, unlike patients wilh retinitis
pigmentosa, who are typically myopic. Because there is
accumulating evidence thal many patienLs with congeni­
tal amaurosis have a retinal dysgenesis associated with
minima! evidence of progressive visual loss., il is useful
to group these patients, who are otherwise normal, aparL
from those with congenital blindness associated with a
host of syslemic disordersr including psychomotor retar­
dation, mental retardation, hydrocephaly, deafness, epi­
lepsy. cardiomyopathy, myopathy, dyscephaly, dwarfism,
and other skeEetal anomalies. |й3_н* it jj possible that
some of these latter patients may have an infantile-onset
progressive tapetoretinal dystrophy.
At birth the fundi of most patients wilh Leber's amau­
rosis are normal. Some palient&, however, may show dys-
pta&tic fundus changes, including pseudopapilledema
(figure 5.4ЙА), optic disc pallor [figure £4SQ),^ab
optic disc hypoplasia (figure 5.^eD),:" macular colo-
boma,"<l6'J56,67;1 and chorioretinal coloboma (Figure 5.4ЙЕ
and Г). A variety of pigment epithelial and relinal changes
develop in early childhood and continue into adulthood,
ihese include salt-and-pepper pigmentation.1"'1, yellowish
Яескв,06^ ^ ” 4^ ^ 1 nmarbieizedv fundus with mosaic
patter]i [E'igure 5.4SC and I],'1' periarteriolar distribu­
tion of well-demarcated yellow lesions located external Lo
the retinal vessels/'1* 1" nummular pigmented lesions
fE'igure 5.4SC ),l:::':,c'1''1 reLi ni Lis pigmentosa/"'1 eh oroide r-
emia,l"’:'' gyrate atrophy,4'’’1-1 macular ^ifobqjiiiuta,-411,356,,fiaa
and bull's-eye maeulopathy.'""1'^1' A variety of progressive
chorioretinal degenerative changes associated with nar­
rowing of the retinal vessels and optic atrophy eventually
develop (Figure and C). Only occasionally does lhe
typical bone spicule pattern of relinitis pigmentosa occur.
Cataract and keratoconus are late complicalions.
The ERG is extinguished in approximately 75^6 of
patients and is markedly abnormal in the remainder. For
infants with unexplained visual loss, an blit; is essential in
differentiating J.eber's amaurosis from other causes of con­
genital blindness/"b E'luorescein angiography may show
evidence of R]?t atrophy not appreciated ophthalmoscopi­
es Ely as well as evidence of papilledema.
LCA is usually inherited as an autosomal recessive trail,
although dominant inheritance has also been reported.
Mutations in ip reLinal genes have so far been shown lo
cause LCA, namely A IP II, CKBl, CRXr EUCY2D, ШУИ,
ЙPE65, KPCRJPJ, TULPJ, IMpDHL and, more recently.
Ь.4 8 Leber’s со nge n iLai a maurosis.
A: This 2 -year-old gid had onLy lijjht perceptitэп in both eyes.
NoLe the anom aly of Lhe oplic disc. Fhe E lH ^ rire tin M fa jfl
was- exLi n^uished. H er refractive error was + -4.^0.
G and C: This- fl-vnar-old boy had hand movements visitfn in
the right eye and 20/70 in [he left eye. Note the extensive
geoj'rapbiс ягель ol atrophy of Hie relinal pi^mcnl epilhe-
lium I Krjt ■posteriorly and the round du m pin g bf pigmenl
in Lhe мИрЕъегу of № fundus. His ftlecbtireti nogram was
esrinLj-ji^hed.
D : O p tic di sc hypoplasia, and m a ile d narrowing of lhe reLi-
nal vessels in this boy with nyslagmus, niyhl blindness., and
arr extinguished electruioLino^ram.
E and F: This 1-1-year-old bay had poor vision з й с е birth,
nyctalopia, marked narrowing of lhe Retinal vessels, pigmen­
tary mottlfrig in lhe macula (E)r marked consLrrclion oF lhe
visual fields, an extrnjjuished electroretinogram, and an infe­
rior colobom ata of the cEwroid and retrna bilaterally I FI. His
i i-ihil .=i i. ■
■■
. v- _:n ■d'il ! J>: In !■■■■ iv i . A lii-l
tousin had poor vision of uncertain cause. At aye 25 yeani
bis findings w ere similar huL his visual acuity was 20/200
bilaterally,
G —I: Coats' syndrome in the left eye o f this w om an w ilh
nystagjnus and marked loss of vision since birth, She bad
marked rrsrroWi'ng of lhe relin-al vessels and exLenbive degen­
eration o f lhe HI’L wiLh pun( tale КГБ hyperplasia (H and I; in
both eyes. En the left eye interiorly there was extensive yel­
lowish exudative dwlachmenL ol" lhe retina and retinal telan­
giectasis |G and H }. Arrows in G and H indicate optic disc:.
J: Hislopathologv of lhe eye of a 12-year-old boy with
Leber's amaurosis and xeroderma pFgmenlcisaJ tvole m ono­
layer of retmiil reoeplors and aEisence oF cone outer se^menls
(anow ) fn the macula, w hich was otherwise unremarkable.
The mid peripheral retina shtjwed disruption- o f lhe normal
relinal aTfhilucture by gliosis.
K: Histopathology of the eye of another patient with Loberb
amaurosis who developed spontaneous rupture of Lhe cor­
nea lhal had severe keratoconus. Note in Lhis sedion of Lhe
peripheral retina lhe marked degeneration ;^nd gliosis, the
m itral ion of Kf’fc {Icfl агГ-oVi inlo I be №fina, 4ind Lhe Local
areas of suEiroLjna: KPh hype rpl asia beneath Lhe rd in a lriL|hl
arrow?.
CEP29Q, because of lhe increasing number of [jtiA-causing
genes., il is difficult Lo classily patienls with LCA on a molec­
ular basis and consequently to evaluate phenolype-genolype
correlations. CSene (herapy trials are underway in СЩЕ65
involved patients. Ejong-tcrm follow-up studies of patients
with liber's ajnaurosis reveal Lhat, although Lhere is a pro­
gression of the fundus changes throughout Eife, the visual
function remains relatively stable in most patienls."''"""'
J.oss of function is most likely to occur in those with macular
cotobomas, and those who in later life develop keraLoconus
and cataracts. Most patients with Ember's congenital amau­
rosis have the capability of norma! cognitive function- but
most perform poorly on standard CQ tests.
In childhood, histopathologic changes consist primar­
ily of failure of develop men L or loss of the rods and cones
{figure 5,4SJ]k Ihese changes are followed by progres­
sive degenerative changes involving all of the relinal lay­
ers and RHl; similar to Lhat seen in retinitis pigmenLosa
(figure 5 .4 8 K Ji^
 lhe natural course of most patients with leber's con­
genital amaurosis suggests that it is a retinal dysgenesis
and not a progressive tapetoretinal degeneration, '['he
progressive fund*>scopic and histopalholo-gic changes
observed in these patients can all be explained on the
basis of reactive changes occurring in lhe retina and pig­
ment epithelium in response to tbe widespread absence
at birth of the retinal receptor cells, t hese reactive changes;
include degeneration, proliferation, and intra relinal
migration of the pigment epithelium; narrowing of the
retinal blood vessels; pro!iteration of retinal glial cells; and
transsynaplic degenera!ion of tbe ganglion cells.
ITie differential diagnosis of liber's congenital amaurosis
includes cortical blindness, achromatopsia, con genii jJ sta­
tionary night blindness, infantile-onset retinitis pigmentosa,
and infantile ceroid lipofuscinoses. Electroretinography
is important in establishing whether the retina is affected.,
and to what degree it is affected. Although the E-RC may
be severely abnormal or extinguished in leber's amauro­
sis, it is not affected in cortical blindness, and only mildly
or moderately affected in congenital stationary night blind­
ness. it may be severely affected early in infantile-onseL
tapetoretinal dyslrophies. Absence of searching nystagmus-
relatively good visual acuity, and absence of high hypero­
pia in these latter patients are features atypical for Leber's
amaurosis. A^ SS3
Neonatal Retinal Dysgenesis and
Dystrophies Associated with Systemic
Diseases
Several well-defined singie-gene defects and other less
Well-defined disorders occur in which retinal dysfunction
is one aspect of a generalized disease affecting other organ
systems. These include Zellweger's cerebrohepatorenal syn­
drome [see p. 397}, Saldi no-Mai nzer syndrome, Senior-
l.oken syndrome [see p. 390), Joubert syndrome (see p.
393), and Arima's syndrome {see p. 39S). Unlike Leber's
congenital amaurosis, hyperopia is not characteristic of
these disorders. Uussell-Lggitt et a!, have reported seven
members of four families nith neonatal nystagmus, poor
vision, photophobia, severely abnormal or extinguished
EJtG responses, cardiomyopathy, and short obese habi­
t u s . S i x had a life-threatening episode of cardiac failure
and two died. Examination of muscle obtained at autopsy
was unremarkable. Mrak eL al. reported a congenital myop­
athy associated with congenital features of Leber's amauro­
sis, hypotonia, delayed motor development, and histologic
evidence of broadened or smeared A bands.^ 1
~r. 49 S lo w ly p ro g ie ss ive d om inan lly 1n h eri te d
d y s tro p h y in a fa m ily w ith n y sta g m u s, m y o p ia ,
m ic r o c o r n e a , S - s h a p e d lo w e r - 1id d e fo rm ity ,
v a ria b le d e g re e s o f v isu a l a c u ily lo ss, fie ld loss,
re tin a l d e g e n e r a tio n , o p tic d isc pallor, a n d
e ie c tr o r e ti n o g ra ph iс a b n o rm a IiI ies.
A-С: Ten-year-old black girl wEth ltd deformity, optic disc
pal I (jt, and juslapapi! лгу Lind peripheral rt'linal pij^menl epi­
lhelium and relinal alrapEw Her electrOlfeiirtogbadhlc sludy
was normal.
D and E: ErotEier, 28 years old, c l palient in Л.
E lectrorefl i nography revealed severely abnormal rod and
cone function.
F: Falhur, 31 years old. of patienl in A. His eleuljoretino^rani
was nonfttordabki.
G : Paternal aunt. 5Ь уеагъ old, of patienl in A.
Electrore<inography revealed moderately abnorm al rod and
to n e functions
H jjnd I: Ei ght-year-old grandson of pa Irent m CJ.
Stationary or Slowly Progressive
Dominantly Inherited Tapetoretinai
Dystrophy
Three successive generations of a black family seen at the
Nascom Palmer Eiye Institute demonstrated an early-onsel.
slowly progressive, atypical tapetoretinal dystrophy of vari­
able severity associated with S-sbaped deformity of the
upper eyelid, microcornea, and angle closure glaucoma
(Hgure 5.43).№: Some of the family members showed
only mild RftE and retinal, degenerative changes with­
out visual Joss. Others had more severe loss of central as
well as peripheral vision. Ibis family shares some features
wilh a dominantly inherited ШЧ: dystrophy with vari­
able expressivity and complete penetrance characterized
by myopia, nystagmus, and an RE4: dystrophy of vary­
ing severity reported by .Noble and associates/''1’ in some
patients the fundus changes were mild and confined lo the
macula. T he severity of the changes was not related to the
extent of involvement or to the degree of myopia. Visual
acuity varied from near normal to 20/200 or worse. 'Ihe
pendular nystagmus was not related to the visual funclion.
Lleclroretinograptiic changes were present in all patients
buL varied from mild to severe. ТЪеве families might
be considered as having a dominant, less severe form of
Leber's amaurosis.
Late-Onset Retinal Macular
Degeneration (LORM D)
Paiiejits wilh Scottish ancestiy were first described with
this autosomal -dominant condition.*^ rYbey are asymp­
tomatic and have normal fundus Lill tbeLr fifth decade.
Symptoms of night blindness begin in the fifth to sixth
decade and progress rapidly over a few years. Early retinal
changes include "dmsenl ikeu yellow spots throughout the
fundus that represent sub-Rl3L deposits (Hgure 5.50C).
Evoon islands of RE4i atrophy ensue, leaving intervening
spacer of RTE that have scalloped edges (J:igure 5.SOD, li..
|-L). The photoreceptor function rapidly worsens over an
average of 5 years to leave the patient With Severely con­
stricted visual fields; central vision is lost later with fur­
ther geographic atrophy of the macular KJJli. There may be
patchy involvement with preservation of the RPE-. in some
parts of the fundus {figure 5.501?.. Lr K, and I.). Larly in
the course of the disease dark adaptation is affected. The
retinal appearance resembles gyrate atrophy; however in
patients wilh gyrate atrophy, the islands of geographic
atrophy begin in the periphery and slowly progress
Lowards the posterior pole, whereas those in LORMD are
present early In the posterior retina, and ornithine and
other amino acids are normal.
Some patienls wilh abnormally long and anterior-
attached lens zonules have been described.^1' Histology,
electron microscopy, and immunohistochemistry show
deposition of material made up of components similar
to deposits in age-related macular degeneration and {SFD
under the -1 |q .iddilion there is accumulation
of esterified (slains with oil red O j and unesterified cho­
lesterol similar to contents of atheromatous plaques, '['he
gene defect has been localized to CTHP5.
j . 5 0 L ate -о n s et ret i n al m a cu Ltr d e g e n e ra lie n
(L O R M D ) .
A—H: This i)2-year-o!d wom an of G erm an descent com ­
plained of difficulty w ilh ni^ht vision for lhe Qast 5 years.
H e r optometrist noted reLinal changes Lhat were not seen
5 years before w hen he had Iasi examined her. She Was
am blyopic in her ri^hl eye hincn early childhood -rind read
2 0/2 DO rif^hL eve and 2Q/50 left eye. Several л ш п т Ы а г aLru-
p h it patches LhaL became larger lowaftfc the periphery п и е
seen in the posterior pole IA and B) and temporal fundus (D
and Ь . The nasal relink showed lino drusen. W in d o w defeuls
were seem on ^il-giograplTy and the lesions w ere hvpoaulo-
Hl h h c s i L Visual fields showed peripheral constriction
and e Iec Цй ret iIngham revealed ?everolv depressed гкя! and
cone ampliludoh in both eyes. Her fa Iher was known (o have
developed poor vision m his laler lift!: she had two living sib­
lings with no visual dysfunction. Two sons a^ed 32 and 34
Were also asvmplomatic..
I—L: This ftO-v&ar-oId H ispanic male complained of nyctal­
opia and reduced central vision for 5 years.. SevuTal o f his
cousins had poor vision,; no history was available aboul
his own sibEings. H is vision was 2№100 and 20/30. Round
patches o f retinal pigment epithelium (RFEj/choriocapiHaris
Пtrophy w ere seen around lhe lovea and diffusely in lhe infe­
rior fundus of both eyes (t-Lj. hatchy pijjmenl migration and
clumping were seen; there w ere inLer\ening scalloped areas
of KKh preservalion lypical of L O R M D ф .
Extensive Macular Atrophy with Pseudo
Drusenlike Appearance
Hamel el л I. described IS patients with an onset before
age 50 of л rapidly inert-rising atrophic macular lesion
that involves the entire posterior pole up Lo the arcades
resembling geographic atrophy of age-related macular
degeneration (Figure 5.51).0:'lhis vertically oriented atro­
phic macular lesion is surrounded by numerous drusen-
lifee deposiLs (resembling reticular pseudod Risen) found
throughout the posterior pole and the mldperipheiy in
all cases (Figure 5.51A-C). All patients also had paving-
stone degeneration in the far inferior periphery. S o patient
developed choroidal neovascularization and the disorder
is not familial.
■
5 . э ! M a c u la r a tro p h y w ith p s e u d o d r u s en,
A-F: This 54-year-old w h ile w om an had a lam ily history of
blindness in the elderly. Onset o f symptoms slarled л I .ij^e
.>0 with -ni^hl blindness, m-arknd photo phobin^ and difficulty
in reading and iace recojjnilion at distance. Her visual acu ­
ity w as right eye: 20У40 with —3.25 sph —1.25 X 170° and
[eft eye: 20/400 with —4.00 sph —1.25 X 180°. Inlraucular
pressure was 13 m m Hg rifjht eye and 12 т т Н р leIC eye. O n
СоМлилпп perimetry she had bilaler-al absolute cenLral sco­
tomas 11. Fj, and dark adaptation was delnyud. BilaltTal lar^e
m acular atrophy With (fee lar^esl diameter in the Vertical asis^
and п и т cjtihis pseudodrusen W B ? нееп in the mid periphery
i A. В . 0pLica5 ccihercmcu tomography showed the alrophy
ot" iht! outyг layers of ihc reLina (D). Pseunodlrlsen were not
autoHuortstent (CJ and were1 ro t vi*ib3e on -angiography or
on Optica] (coherence tbmogfaplry1.
[Сйцрееау erf L)r. Oiriiliiin' H ;irnr:l. -
.ItyfJj'oiJ Porm i i’ f PigmetitQSfl 35 7
West Indies Crinkled Retinal Pigment
Epitheliopathy
Recently. a novel retinal dyslrophy (]:igure 5.51) Was
reported by Cohen et al. (presented aL lhe Macula soci­
ety an null meeting, February. 2010). All reported patienls
were black of from black ancesiryr and originated in
Martinique, a Trench West Indies island. The disease
affected a whole family of an й6-year-old mother and her
four children. Two other patients were diagnosed wilh lhe
condition, one related [cousin] lo this family, and one
unrelated, bul originating from the same geographic area.
The main fundus feature is the presence of a while
reticular net located at the level of lhe Ri'L. dense in the
macular area, but also present in the midperiphery, resem­
bling crackled diy mud [figure 5.52A-C). Some pigment
may be observed wilh in lhe relicular pattern either in the
macula or the periphery. Autofluorescence pattern is vari­
able, wilh Itypoau to fluorescence of the white lines (Jigure
5.52D). tluorescein angiography reveals a hyperiluores-
cent network pattern in lhe early frames, with lale stain­
ing (I'igune 5.52Т-П). Indocyamne green angiography also
displays the reticular pattern on tale frames (Hgure 5.521).
On OCT the R]>H appears rippled, giving the crinkled
appearance (t'igure 5.52]). The etiopathogenesis of lhe
disorder is unclearr be il an acquired or a dyslrophic con­
dition. Two patients developed subrelinal hemorrhages
related to possible polypoidal choroidal vasculopathy.
Two patients also had disciform macular scarring which
may have been secondary Lo hemorrhages andfoF choroi­
dal neovascularizalion. Eilectrophysiology and genetic test­
ing a re origoing.
5.52 West Indies crinkEed relinal pigmenl
epilheliopathy,
Л .ind E: Composite of ri^hl and ]efL eye oj a patient w ilh
crinkled corrugaLions of Lhe lelinal pij’menl thpiLhelium
appealing as a w hile retitular re t more densely packed in
Lhe m acular area buC ел I ending to the ttiidperip№ry, rasem-
blinjj. a crackled dry land. M ild pigmentation of the corruga­
tions in lhe fovea and periphery.
С—I: Left eye o f a second pa Lien I showing the distinct crin­
kling ECl. The auloFluorescence is variable,; mosl of the
wrinkles correspond lo hypoautol luorosicence ^uggesLing
displacement of retinal pi^menl epi I helium Kl'Lil pii^nrml
nwny from lhe wrinkles ^similar to lhal seen in choriorMinal
fuldi) (Dj. Fluorescein angiography revealed lhe w rinkle lo
be ЬурегПиогеьсегН, ajjain s-u^grfsLing relative Заек or" pig­
ment w ilh in I hi? Ft^E (El w ilh lule Hlaining ■
;F-j. Kight eye of
lhe sam e patient shdWetl evidence of choroidal netivascular-
i^alion w ilh subrelinal hemorrhage tC and H). Indocyafltltp
green angiography showed a retfcular paHSHfn on Iale frames^
Ljli1 lens disLinelly O ptical coherence tomography showed
LhaL Lhe EiFE was thrown into ripples, giving the crinkled
appearance (Jj. Electm physiology and genetic testing is
ongoing.
(Cfr-lrlesy oE Uri. :SY tdhtfn, A Ju.in-(Jhi.-irltfK, .Mill hi M i t Ic
CHOROIDEREMIA
Choroideremia is a X-linked recessive chorioretinal dys­
trophy. ,l5I"7Lj il probably Lb lhe same disorder reported
previously by some authors as X-1inked choroidal sclero­
sis. '' Affected males usually note the onsel of nighl blind­
ness between 10 and 30 years of age. Some years later they
become aware of loss of peripheral fields. Central vision
es affected only in middle or Jaler life. Molded depigmen­
tation of lhe ftPL may be lhe only finding initially. Large
patches of ftPE and choroidal atrophy, however, develop
in the ni id periphery of the fundus and spread gradually in
anterior and posterior directions. Eventual by Lhe palient is
Eeft with only a small island, of relatively normal choroid
and R[Jt: in the macular area (Hgure 5.53] and J, anti 5.54V
and L.). Choroidal neovascularization may rarely occur.
ManAwLng of the retinal vessels and optic atrophy accom­
pany the later stages of the disease. fluorescein angiog­
raphy during the lale stages of the disease demonstrates
slowing of the relinal and choroidal circulation, marked
loss of the Rl'iL, and choroidal vasculature, but relative
preservation of Lbe and the choroidal vessels, includ­
ing the choriocapillaris in the central macular area (Ligure
5.53b]). Angiography usually demonstrates the presence of
many choroidal vessels that may be difficult Lo see opb-
thalmoscopically Some patients .show severe impairment
of the photopic functions in dark adaptation. Color vision
is essentially normal. ihe LKC is abnormal early and
becomes extinguished usually by mid life
'llie female carrier demonstrates normal visual acuity,
visual fields, dark adaptation studies, and eleetroretino-
grapbic findings nind. wilh few exceptions, shows character­
istic RPE mottling and depigmentation that is most marked
in the midperipheiy (figure 5.53H and C G and M, 5.541:
and K). lhe pigment granules in carriers have been described
as being irregularly square in appearance. rltte pigmen-
Lary changes are not associated xvith abnormalities of either
the optic nerve head or retinal vessels, lhe fundi resemble
those seen in rubella retinopathy (see figure 7.27] and
Lo:tie retinopathy caused by thioridazine [see ligure 9.02A)
but are different from the streaky iridescent changes in Lhe
fundi of some carriers of X-l inked retinitis pigjnenlosa.
j.53 Choroideremia^
A: A 33-year-old man w ilh visual acuity at 2(V4t) in lh e ri^hl
eve and 2Q^0t> in lhe fefl eve had £ liters lye alidpby al" Lhe
choroid лrrrJ relinal pi^Tnenl epilhciliu-im i HPE'i in bolh eyes.
There w a s preservation ut name of [he RKt centra IK' ■Mrrow.
Al. 1 he retinal vessels Vtitfie narrowed.
В and C: Carrier state of choroiderem ia with widespread
inoLlliny at the KFJt thrau^houl lhe hindus Of и 9-yoar-old girl
with normal ■ . ibuaf acuity. Her father had с horoi doncin i а . Her
electro-oculagraphic Hnd e]ecLroretjnogjaph]c findings w « e
narnial.
D and E: ChoroklerLfinia in a Э4-уеа г-оГН man. Visual acuity
was- 2 0/25 in I he riyhl eye and 2 D/20 in I he left eye. H is el ec-
trorel i nogram was ejtSin^uiHhed. His brother was; srrnilafte
affected. Two sisters had pigmentary changes in lh e fundi but
normal visual function.
F-J: This 34-year-dld wom an com plained of mild metamor-;
phopsia in f:er right eydi: Visual acuity was 2tA<25 in the rii^liI
eye and 2 0 /2 0 in the lelE eye. She gave a history of "relini-
Lis pii’menioha" associated with fartg-standing nycbilopia in
her father. Both eyes had slippled pigmentation resembling
'"cracked d a y " tF-H). Her visual fields were full, and elec-
troreli nogram was normal in both eyes. A diagnosis o f car­
rier fitala o f choroidenumia was made and father asked Iо bo
evaluated. Father had diffuse loss of pigmenl in lhe fundus
with preservation o f Lhe RKE in the fovea, nan ow ed retinal
arteries, severely constricted visual fields and a visual acuity
of 20/bO in each eye ! and J). The findings were lypical of
chomi donum ia.
[L-Jj-Al*t}, Viflhrtuiilt. LaUA*tlBS!., fht fttlihiil AlLs^ SJuHiJl i j ГОЮ 57fl-
П - 7 П 2 П - :к 5 2 1 1 - Ч , p . I 4 f 5 . |
It is important lo identify these carriers because their
sous will have a 50% chance of having choroidcremia and
their daughters a 50% chance of being carriers of the dis­
ease. Some female carriers are known lo manifest clinical
features of choroideremia, especially later in life due lo
irregular inactivation of the X chromosome (lyonizalion).
No known systemic association has been described in
patienls with choroideremia, except for one male with
polydaclyEy, which was caused by an autosomal-dominant
inheritance of polydactyly on his paternal side. Me had
normal growth, normal mentation, and no evidence of
hypogonadism. M
 ChoroEderemia is caused by mutations in Lhe С Ш
gene localized tо the long arm of X-chromosome
(Xq2L2). lhe mutation affects the production of Hab
escort protein iso form 1 (REP-IJ, previously kncuvn as
component A of Eiab geranylgerauYltransferase (GGfaseJ,
the enzyme that plays a key role in the activation of Uab
proteins that are responsible for the regulation of exocytic
and endocytic cellular pathways, they control the protein
trafficking of secretory and endocytic pathways. Л reduc­
tion in particular of activated Kab27a by preferentiaE bind­
ing by RE: EM is implicated in choroideremia.'1^ 151 Several
types of mutation in the СИМ gene, including point dele­
tion^ l.irge basepair deletions, splice site substitutions,
and transfocationsv have been associated with the cEini-
caE findings of choroideremia.. ]hough these patienLs lack
1Ш М iti all other cells loo, the retina and choroid are the
only structures affected in choroideremia: il is believed
that RL!*-2f that resembles JEtEIM to about 75v/a is enough
to activate Hab proleins in cells outside the retina and
choroid .1|,J
DMA analysis of chorionic villi obtained during preg­
nancy permits prenatal exclusion of choroideremia. 20
Histopathologic examination during the late stages
of the disease reveals atrophy of the choroid, RPIi. and
overlying retina with relative sparing of the macula and
r
L J
j.54 Choroideremia..
A —L: A 15-year-oEd boy was found to have mild visual field
constriction on n rouline Humphrey field tes) done at лп
optometrists office. His visual acuity WaS 2 0/2 Q in each
eye. Tbere way diffuse loss oi piemen I in [he fundus in each
c^-ye sparing I he centinl macula. £(nall pigmenl clum ps
were seen here and there in I bo fundus iA-C). His 8-year-
old half-brother was also asymptomatic and bad fine pig­
ment stippling in the fovea and moderate loss of pigment in
Ihe midperiphery and anterior fundus in each eve (□ . Ih eir
40-year-old mother wan asymptomatic w illt 20/20 vision
and an almost normal fundus appearance iL). "their УЗ-уеаг-
old maternal grandfather had lost his right eye I о advanced
glaucoma, and the left fundus showed complete absence
of pijjfnenlj narrowed retinal vessels and a visual acuity of
20/400. The fundus 3 уеагь Liter showed further loss of reLi-
nal pigment in both half-brothers (О-]), normal pigmentation
in Iheir carrier molher iK , and complete absence (if retinal
pigment in their grandfather ■1_:.
■(.' ,]nd H.. .■'lImJ, YllVinn^il, l.LViTL'I.Lf I., I Ht'ti n.il All .lb, i.LUinlrjr^-2fi ED,
37;tO-7li2()-3j2Ci-9, p.147.)
periphery. Llltrastructurallyr the cur­
vilinear trilaminar structures ivithin macrophages in
the RFK and outer retina are similar to those seen in
abetalipoproteinemia.11
 The retina in a symptomatic female carrier displayed
areas o f severe degeneration, vxrilh complete low of pho­
toreceptor outer segments, photoreceptor nuclear atro­
phy. and atrophy of the inner retina interspersed with
near-по по aI areas, in affected regions, the R[4i showed
severe degeneration, with thinning, pigment clumping,
and deposition of subepithelial debris, lhe choroid was
depigmenled. E.abeling With cone opsin and rhodop-
sin antibodies revealed that cones and nods Were severely
affected. Wltrastructurally, RPEi apical microvilli and basal
in foldings were absent in the macula and handed fibers
composed of clumps of wide-spaced collagen were present
on the RPE s basal surface and choroid. JJruch's membrane
was fiEled wilh vesicular structures, some smooth and oth­
ers with bristle-1ike projections.
The differential diagnosis of choroideremia includes
diffuse choriocapillary atrophy, which in some cases is
dominantly inherited,"1' and gyrate atrophy of the cho­
roid- which ts associated with hyperornithemia and auto­
somal-recessive inheritance.' 2i figure 5.55 illustrates a
;"undus picture simulating ch oroide remi a in two unrelated
women with late-onset visual loss and a history of sibling
in v o lv e m e n t Amino acid analysis, mode of inheritance,
and oim lnatiD n of the mother's fundus are important if
Lhe diagnosis of choroideremia is uncertain.
Ь. з j Non X-linked choroideremia.
A -F: This 5 B-yea r-ol d w hile wom an noled lhe? onstrt qf visual
las? at agu 4 Я years. The* visual loss bad buen si able for
years.. 5 he had one sister w ilh the same eye disorder. Two
р г й т м ? had normal eyes. 1he paLLenL's visual liil1,’ in Lhe
right e ye Was 20/50 and in the left eye 2(У200. Her finjjer-
cjounlin^ field peripherally in both н уж was full The chofoid
and retina near lhe Equator and beyond appeared norm .iI.
H e r eieclroretinugram revealed markedly reduced rod am pli­
tudes wiLh delayed Liming and moderately niducud cone
amplitudes with delayed timing bi laterallv-
G and H: This 5fl-year-old Latin wom an was asymptom-
alic al a^e 44 years w hen she was told that she had e v i­
dent!1 ul" rulinilis piemen losa. She had noted Lhe gradual bul
severe loss o f vision sinue a^e 53 years. Visual acuily in lhe
right eye w as hand movements and in lh e IeA eye 2Q/200.
Goldman*} fie Id к revealed preservation of siime peripheral
visuj.i ln'lri :i ■.111■ 111 . I l :f u rd u - lird u>|s w itc- almm t iden
Lical to those shown in A-F. There was a history of similar
eye findings in four of 10 siblings.

Non X-Itnked Choroideremia

Several women have been seen with diffuse chorioretinal
atrophy (l:ig. 5.55) without a family history of X-l inked
choroideremia. They do nol have Turner's syndromef XO )
or be a product of an affected faLher and a ch oroide re mini
carrier mother. It is likely that they have a disease different
from choroideremia, and future genetic analysis is likely lo
yield a cause.
C O N E - R O D D Y S T R O P H IE S
(IN V E R S E P IG M E N T A R Y R ET IN A L
D YSTRO PH Y)
I.ass of centra] and color vision and development of nyc-
Lalopia, usually early in life, are the hallmarks of cone-
rod dystrophy l::'4 Иле onset of symptoms
may not begin until adulthood (Hgure 5.56A). Initially
some patients may manifest only clinical and electro-
physiologic evidence of cone dystrophy (see p. 306). In
the beginning the KPL in the macular area may be normal
(t'igure S.S 6F and t".). Later, mottling of the pigment in
the macula along with slight narrowing of the retina! ves­
sels occur ' 1Ъе pigmentary changes progress and may or
may not be associated with bone spicules in the periph­
ery. A bull's-eye-like pattern of pigmentary derange me nL
frequently develops centrally followed later by temporal
pallor and capillary telangiectasis of the optic disc (l:igure
5.5GA. В, H, and !3}. ''' lhe l:RG, however, usually reveals
markedly abnormal or absent cone responses and reduced
rod responses. It may become extinguished. The HOG
is flat. '1'hese patients show severe abnormalities of color
vision. Jhere may be some value to suhclassification of
these patients into groups depending upon the relative
severity of the reduction of cone versus rod LRC ampli­
tudes. " n Vitreous fluorophotometry is less likely [o be
abnormal in these patients than those with typical retinitis
pigmentosa.'3''
Cone-rod dystrophies are a heterogeneous group of
inherited disorders. Flhey may be inherited by all three
main modes. The four major causative genes in the patho­
genesis of cone-rod dystrophies are A8CA4 [which causes
SLargardt disease and also 30-60% of autosomal-recessive
cone-rod dystrophies), CSX and GUCY2D (which are
э .5 б Cone^-rod d y s lr o p h v
A -С: ip o rad ic Lite onset of cone-rod dyslnopEiy in this
3 t -year-old man w ilh л 27-year histoTy a l nyctalopia and л
l -уелг hislory сГ visual loss. Visual acuity, w hich а! I be age
□t 2S was 20/20, was n<iw ^СУ400 in Lhe right eye \A' and
20/20 in- lhe lefl eye His efettroneliitographic findings
revealed severely abnormal rod and tu n c responses.
D and E: Earty-onset cone-rod dvslrophy in a 12-year-old
boy with peripheral bone corpuscular changes in the retina
and a noruocordable electrorelircogram. His visual acuity
was 24/200. A brother had similar findings. Note bull's-eye
p j Item of relrnal pigmenl e p ilhelium :RPE:. illnc>phv_
F —I: Cone dystrophy, probably progressing to a cone-rod
dysLrophy, in a T7-yeai-old female w ilh progressive spino­
cerebellar degeneration and spastic quadriplegia. She noted
progri.'s-si ve IOS'S ot" vision beginning a I age 14 yEars. Her
visual acuity was 20/2 00. An etectrofeLrnojram showed
markedly л Ьп о тта] cone time I ion and norma! rod funcLion.
H e r fundi it and и n giogja pliv It.!' were w ilh in normal lin v
its. AL 22 vears ot ago.. Ь н vision had doc rented further and
Lherii was narrowing ot lhe retinal vessels and widespread
KF't changes (H i. A ngicgr лpEny ill revealed a bu1l^-eye pat­
tern ot hyperfluorescence in I he macula of bolh eyes and
evidence or" diffuse aLrophy of lhe КИЕ.
responsible for many reported cases of autosomal-dom­
inant cone-rod dystrophies and cone dystrophies), and
kPGR {which causes about two-thirds of X-linked reti­
nitis pigmentosa and also an undetermined percentage
of X-linked cone-rod dystrophies).' ' 1 Et occasionally is
associated With neurologic disease (bigure 5.561'-E). JJabb
et al. reported the clinicopalhologic findings in a patient
with cone-rod dystrophy.'_ъ 'Ihey can also be part of a
syndrome such as Eiardet-lliedl and SC A 7. A similar dis­
ease in baboons and Rdy cats has been studied by light
and electron microscopy." 1 " 1,1 Deletion mapping of a
cone-rod dystrophy resulted in assignment to Itfq 2ll.' '
О т 1—Кл\{ Dif^trcrhics (inverse Pigrtiailary Retmid Dystrophy) 3G /
Goldmann-Favre Syndrome (Enhanced
S-Cone Syndrome)
Goldmann-ravre syndrome fhya Ioideotapeto retinal
degeneration) is an autosomal-receive disease character­
ized by night blindness, atypical peripheral pigmentary
dystrophy, central a n J peripheral relinoschtsis, compli­
cated caLaract at an early age. optically empty vitreous with
an occasional vitreous band, and a markedly abnormal,
often nonrecord able, ERG.7Jti_:’‘N In addition lo narrowing
of the retinal vessels and waxy pallor of the disc, Lhe mac-
uJa appears diffusely thickened by prominent superficially
Located macrocysts that fail to it ain on fluorescein angio­
graphic study (figure 5.57C, t r and P). Ciiant macular schi-
sis and cyst formation can be confirmed on 0 С Г testing
(ligure 5.57J-1.). Ibere have been reports of benefit with
oral acetazolamide in decreasing the macular thickness in
patients with enhanced S-cone syndrome.
Cases of night blindness and peripheral retinoschi-
sis without macular schisis occur/^ 3-listopathologic
examination of a peripheral biopsy specimen in one case
showed nonspecific degeneratioEi of the sensory retinal
layers, thickened retinal vessel basement membranes,
areas of retinal vascular occlusion, preretinal glial mem­
branes, and choroidal 4rascular changes."N Some patients
with CjoJdmann-]:avre syndrome demonstrate relatively
enhanced S-cone function electrophysiologically identi­
cal lo that found in the enhanced S-cone syndrome/46' 1,4J
']"hese latter patients have night bEindnessr maculopathy
(often cystoid), degenerative changes with partly pig­
mented yellow flecks in the region of the major vascular
arcades, relatively mild visual field loss, slow progression,
and a characteristic ЕЙ0/ !"lb e dark-adapted ERG shows
no response to low-in tensity stimuli that normally acti­
vate the rods but large, slow responses to high-intensity
stimuli. The large, slow waveforms persist without change
under light adaptation and show a striking mismatch Lo
photopicaliy balanced short- and lottg-wavelength stimuli.
With sensitivity much greater to short than to long Wave­
lengths it is possible that patients with G old man n-E'avre
syndrome and those with enhanced S-cone syndrome,
some of гг bom do not have macular schisis, are not dis­
tinct entities but are simply two identifiable phenotypes
of clinical expression of a reLinal degenerative disease
with a single pattern of retinal dysfunction. Patients with
both syndromes have been observed in the same fam­
ily. I here is evidence that patients with the enhanced
S-cone syndrome have a retinal dysgenesis that prob­
ably occurs during the early development of the retina
and results in many more S-cones that form in the place
of many l./M-cones and rods."10 Many of the clinical and
functional characteristics of enhanced S-cone syndrome,
e.g., the negative wave form, reduced osci 11atorv potentials.
5. >7 Goldmann-Favre syndrome (enhanced S-cone
syndrome^
Л-C: Th is 19-year-old boy's YisuaT a t oily in Lhe rijjhl eye
was- 2 0/50 Lind I-1 and in Lhe left eye was- IQ/200. H e had a
mid ^onal scotoma. There w e iE extensive schisis and large
tystoid changes of" lhe entire macular region .AJ. There was
a broad mid jo n al area of alrophv ol I ho relinal pi f^rn-^nI
epithelium .'г - м :.11■ I w ilh fo nu 1 m iдтлIion ■■Г :ill”i:•"!iI .'in:;
narrowing of Lhe retinal vessels (B). ThertL was no peripheral
relinoschisis. FFuorescein angiography (C) was within пог­
нил! Jim its. There whs no leakage oL dye in thjj late ttages of
angiography. His elecCrorelinagram showed absent photopic
responses and markedly abnormal KcoLopk responses. His
color vision was normal I'FamnworLh U-151.
D-F: Coldm ann-Favre disease in a 12-year-old boy com-
plaLning of mild loss o f vision. His fam ily history was nega­
tive. Visual acuity was 30/40 in lhe riyhl eye and 20.'iOO ir>
Lhe left eye. He had tpfirtaj thickening and cystic changes
throughout the m acular areas ID:-. There wore ill-defined
subretina I w hite flecks I a nows, U and El in the perimacu-
lar area. Angiography revealed focal areas of liyperfluores-
cence corresponding w ill: lhe fftrcrkь (arrow, t- and F). lh ete
Vuai no evidence of in Ira ret in a I slaining. An eleclroretino-
gram shewed severely abnormal rod and cone funcLion.
The elecLro-oculographic fmding^ were markedly abnormal.
EiyhL years Ia Let lhe fundi were unchanged. Vrsual acuity was
20/400 and |-.'i in lhe righl eye and 2 0 в 0 0 and 1-2 in. lhe left
eye.
G-L: Tinis presen I 30-year-old male was examined by L>r.
Cnis-s aL ayq E9 w]th a hisLoTy of running inLo Eju h Iio s when
Lhe child goL oul ot Line car in Lhe dark tor lhe previous 10
years. Al LhaL lime he carried a diagnosis of juvenile m acular
scbrsis in botli eyes. H e was found Lo have a disciform scar
in lhe m acula ot" the righL eye and extensive schisis in Lhe
macula o f the left eye rephо Lographed al age 30 fCj and Hi.
He also had pigmcnled nummular tesibni (arrow I soilnound-
ing lhe arcadcs in each eye i[ and )l. The reLinal vessels. were
of reasonably caliber and no bone spicule pigmenl migration
was; visiEile in eiLher eye. Л diagnosis of tloidm aiin-Favre
Lenhanced i-cone dystrophy) disease was made by Dr. Cass.
O ptical coherence tomography shows- a scar from invo I и Led
choroidal peovasculbpt membrane in Lhe righL eye wiLh co l­
lapsed schisms and extensive schisis ol lh e left macula extend­
ing up I о Lhe arcades (K and L).
relinoschisis, and vitreous changes, may be consequences
of this early ab normal tty in Lhe complex development
sequence of the retina. :fl Eiolh patients illustrated in
Hgure S. 57 (A-H) reported in previous editions of this
atlas as еяатр 1е& of Coldmann-l'avre syndrome were
recalled and both have enhanced S-cone syndrome.
Mutations in \\R2E3 which encodes a photoreceptor
nuclear receptor are responsible for enhanced S-cone syn­
drome, Goldmann-Havre syndrome, and clumped pig­
mentary retinopathy.
Familial Foveal Rqtin orchis is
l^veal rednoschisis, which is characterized by a delicate
network of radiating cystic changes in the superficial retina
and confined generally Lo the foveal area, is the halEmark
of X-linfced juvenile retinoschisis and should be differenti­
ated from macular schiyis., which is composed of a more
coarse pattern of larger cystoid spaces that may extend
throughout most of the macular area and is the hallmark
of Gold mm n-E'avre syndrome. With rare exceptions. ■
v 7-year-old boy w ilh a rhejjrnatojjenuus retinal detachment.
famitial foveal retinoschisis is found only in males/5*1
77tr Ihe jnacula is involved in all cases, and many patients
demonstrate evidence of widespread changes in the retina
and K PL
X-Linked Juvenile Retinoschisis
A consulnt diagnostic feature of X-Linked juvenile retinos-
chisis, which is present at birth or soon afterward in all
affected males, is a characteristic macular lesion referred
to as "foveaE schists* (Tigure 5.5SA. C, G, |. and L and
5.5УА-С, fc-G). Only 50% of patients will have evidence
of peripheral reiinoschisis or related findings, mostly in
the inferolemporal quadrant {figure 5.5&A, Ei, |, and K).
Ihere may be lar^e ovaL or round holes in the inner reti­
naE layers creating "vitreous veils* (figure 5.58b). Retinal
hlnod vessels may or may not accompany (he inner reti­
nal layer Unsupported retinal vessels in ay course into the
vitreous cavity. Semi translucent gray-white arborescenL
scrolls, a dendriform pattern of occluded retinal vessels
(figure 5.5831}.. silver-gray glistening patches on the retinal
surface, perivascular cuffing, chorioretinal scars., vitreous
detachment, intrarelinaL gray-whiLe spots [figure 5.5tiG}..
э л К X-linked juvenile reiinoschisis.
A and E3: Typical Tadialin^ inner rulinal evils associated u-i1h
fa veal tchisis ir a boy wi)h peripheral retinoschisis and lari^e
holes in the inner re iin il layers.
С and D ; fuveum acular schis-is in a 24-уеаг-ик1 man w h o
firs) noLEsf decreaaed vision at aye 5 years. Visual acuity was
20/30. An^io^raph\ shnwud -minima] ч lianytw in- Ihe relinal
pifjmtmt epil helium.
E and F: Cystic changes simulating fuveaf reiinoschisis in a
Thesedis^ispefllfefcl after a sc I era I b u ck in g procedure.
G - l: Fuveal and- peripheral retinoschisis in a 14-year-uld buy
with widespread inlra retinal у ray-white spots and shealhed
Lind occluded peripheral retinal vessels. There w ere lari^e
holes in I he inner retinal la y № temporally i n 1h-t! fi^ht eye.
]-L: Twenty-«S»-year follow-iip of X- linked juvenile relinu-
Hc.bisi-н in a paLient V/hn Was aye 15 years with visual acuity
o! 20/60 bilaterally w hen Jiisl seen with fovenm acular ichisis
l.l and К I. Visual acuity at last exam ination was 20/200 right
eye and 20/BO left eye. There was minim al change in the
fundi flit
intraretinal blood cysts. and evidence of recent or old vit­
reous hemorrhage are other findings that may be present.
Nasal dragging of the retina may be present in infancy
and is presumed Lo be related to temporal dehiscence of
the nerw fiber layer.' lieltnal and optic disc neovascu­
larization may occur.' Usually these patients are ini­
tially seen during the early school years, either because
of reading difficulty or because of symptoms of vitreous
hemorrhage. An occasional patient may be seen early in
life because of a massive area of schisis that partly or com­
pletely obstructs the pupillary space.
 Uio microscopically, foveal schisis presents 4 characteris­
tic picture of smaEl superficially located cysts arranged in
a stellate pattern and radial striae centered in the fovea)
area (Retires 5.5dA,. C, G, }, and L and 5.59C., L, К and C).
ihe central cysts often have a fusiform shape. Additional
cysts become evident more peripherally. This is associ­
ated with some elevation of the inner portion of Lhe ret­
ina. A peculiar sheen develops on the retinal surface, Ihis
occasionally may presen L a golden tapetal reflex and the
Mizuo-Nakamura phenomenon.' " Eventually the cyst
walls may coalesce and form a large central schists cavity.
Jhi& is followed in some cases in adulthood by disappear­
ance of the cystic changes- alterations in the underlying
KJ4i. and finally development of a nonspecific atrophic
macular lesion. Some patients demonstrate corrugations
of the outer retina either in the temporal macula, or more
extensively throughout the fundus These corrugations
appear to be at the photoreceptor and outer plexiform
layers and are known to change in orientation and shape
over time,, and sometimes may disappear altogether. Two
brothers arc shown in figure 5.59. The younger sibling,
who became symptomatic first, lost the corrugations over 5
years (figure 5.5911 and Kj. Whether the change in height
and Lautness of the schisis cavity imparl forces to the tem­
poral retinal to cause Lhese corrugations is a hypothesis. 1,1
Some pa Lien is show progressive narrowing of the retinal
vessels and develop peripheral changes of pigmentary reti­
nal dystrophy, in childhood the RPE may be normal (figure
5.58С and L>) or may be diffusely or irregularly depig-
mented (figure 5.5S| and K). Rhegmalogenous detach­
ment Infrequently occurs, and spontaneous realtachment
may occur Jlupture of a superficial retinal neovascular tuft
within the area of schisis may cause either vitreous hem­
orrhage or bleeding into a peripheral retinal cyst/ '5 Most
vitreous hemorrhages resolve spontaneously. Anomalous
vascular looping or branching on the optic disc is common.
Most of the changes occurring in X-l inked juvenile reti-
noschisis occur during the first two decades of life. 80 Visual
amity often stabilizes at 20/50-20/300. lhe peripheral visual
field is affected only when peripheral schisis is present.
On fluorescein angiography the posterior fundus is fre­
quently normal [Figure 5.5SD}. In some patients there
j .59 X-1in Iced j uve n ite re I inosc hisls an d q uter re tinal
corrugations.
This 12-уеат-old male ■sibling A I h.ad л besL-corrutled visual
acuity (if 2Q/60 in each eye. There were cystic changes in
lhe fonea in bolh eyt;s, more prominent on Lhe ri^hl i.A.i I him
the left. In addition corrugations ol the oulor retina w ere lik­
ened lo "flying sua^uirs'1' temporal Lo the sc bis in cavilv rn his
EefL eye fB). His mother's eye examination was normal. His
vision gradually worsened over 5 years to lhe 20/200 level.
Five years later bis brolEier o lder by 2 years LsiblLn^ В I noted
a rapid change En vision and could not tie corrected with his
contacl lenses beyond 20/40. He bad fov^al schisis in bolh
eyes ^ssocUt^d with similar ouL^r nelinnl corrugations, in bis
right eye (C and E). The schisis tSVSty was noL detected by
fluorescein angiography, w hile Lhe corrugations w ere m ildly
fluonescenl iJJ. arm w j. O ve r lhe nexl ve?ar lhe conu^alioris
changed in shape in his riyhL eye and appeared in Lhe left
eye (arrows, H and C:-. O ptical coherence lomo^ruphy (O C T '
of bolh m aculas showed schisis Cavity [n m ulliple layers :H 1
and I-C2 i. O C T through Lhe corrujjalions showed Lhem lo be
in lhe outer retina wiLh processes of the photoreceptors and
esternal limiting membrane Iarrows, 11 and 12 . Sibling A
now had lonL lhe mliiTal corrugations in his left eve, lhe schi­
sis was more Widespread in E>oth eyes (f and К . and lhe O C T
showed schists cavily on Lhe LefL was larger ■L.i.' ' u
may be diffuse mottled hyper fluorescence indicative of
extensive pigmentary changes present throughout the ret­
ina (figure 5.32J and K). Patients wilh evidence of periph­
eral schisis may show leakage of dye from the retinal
vessels within the area of schisis, as well as adjacent areas
{figure 5.581}. Evidence of nonperfusion of segments of
the retina may be present. ОСГ demonstrates the cavi­
ties with vertical pillars separating them from each other
(figure 5.53111 and 112). Dark adaptation is usually nor­
mal or minimally affected. Electroretinography typically
shows abnormal b-wave acid normal a-wave amplitudes,
prolonged b-wave latencies and implicit times, reduced
oscillatory potential generated by either rods or cones.,
and reduced 30-1 lz flicker response. ''"The findings are
probably parity dependent upon the severity of the reti-
noschisis and the age of the patient. lilectro-oculographic
studies are usually normal in young patienls.Iltey may be
subnormal in patienLs wilh severe involvement of the HE1El.
О т 1—Кл\{ Dif^trcrhics (inverse Pigrtiailary Retmid Dystrophy)
 I LLsUjpлthoLogicLT.11y, the splitting in juvenile retino-
scbisis occurs in the nerve fiber layer and g£nglion cell
[avers.'1"" ' l,‘' ?ai The internal limiting membrane of the ret­
ina is thinned over the area of schisis. '['he inner layer may
or may not contain retinal blood vessels, lo date no his-
topathology is. available concerning the typical early stages
of foveal schists. The histopathologic findings and LRG
ah no rn] aLilies affecting the b-wave implicate the Muller
cells at the primary cell involved in this disorder. eQ'7SJ
(See p. 50& for (he histopathologic findings of infantile
cystoid maculopathy that macroscopically resemble foveal
retinoschisis.) Unlike senile schisis, xvhere retinal splitting
occurs predominantly in the outer plexiform layer and
adjacent nuclear layers, the superficial juvenile retinoschi­
sis cavities do not conLiin acid mucopolysaccharides.
Progression of visual loss is usually slow and may be
associated with minimal changes in the appearance of the
fundi {Figure 5.5BJ and L). Peripheral schisis usually does
not progress, and in щ ш е cases spontaneous reapposition
of the inner and outer layers occurs.
There are no fundus changes in the female carri­
ers.'1 Arden et at. reported identificalion of obligate het­
erozygous X-linked juvenile retinoschisis: all patients
demonstrated a lack of rod-cone interaction electro-
retinographically.'61 Linked LJNA probes have been used
for carrier detection and diagnosis of X-linked juvenile
retinoschisis. ■
Mutations including deletions, missense mutations,
and null mutations in the lletinoschisin gene X k L S i are
responsible for the condition.
Koveal schisis may be simulated by focal contraction of
Lbe interna] Limiting membrane caused by contracted pre-
foveolar vitreous cortex following an aborted macular hole
(see Hgure ]2.I4|-E.), by changes occurring in the inner
retina in patients with a rhegmatogenous retinnil detach­
ment (Figure 5.326: and FJ, and by in far] tile cysLoid m aa l­
lopathy (see p. 506).
Bullous peripheral retinoschisis affecting the macula is
seen mainly in infants and children and there is a marked
Lendency for spontaneous resolution. Prophylactic treat­
ment to prevent spread of the schisis or to reattach the
inner retina is generally unnecessary and may lead lo
severe comp Iieations.
Non X-Linked Foveal Retinoschisis
Typical foveal schisis has been reported in females with
peripheral schisis/^ and in families showing evidence
o f autosomal-dominant inheritance (Figure ,-'4,' :’1'
Jhe paltern of the foveal cystic changes is variable (Figure
5 . A. Ei, G, and H); some resemble cystoid edema in
patients with retinitis pigmentosa whereas others have
more vertically oriented columns of tissue between lucent
spaces [E-'igure 5.-6IJ. Lewis and associates have reported
typical foveal schisis in three daughters of a no neon san­
guineous marriage. '"I' Yamagucbi and Нага have reported
5.60 Non X-linked roveomacular schisis.
A-С: Fuvuonia lu IFif schisis fn а 19-year-old wfim afl
with visual acuity 20/20 right eyer and 2Q/40 1еЛ eye.
Anjjiojjraphy was normal {G>. H e r family history was nEga-
ii№ . Her eledroretinographic study was normal.
D-l: Familial foveom-acular schisis in a brother -and sister.
Macular lesions w a r iksL noled in the sister al a^e b years.
Al atje 1^ years her acuity in the rigEil еуй was iUOO bffaler-
ally. bhe had mild ^paretinal m^febrane changes and cystit
Hyeal c h a n t s bilaterally 1-h<al wt're assonaLed with а yel­
lowish change at (he level of the reEinal pigment epithelium
i K.P1: > in Ihe rij^hl eye (.1Э and E). A Few vitrwjus cells ivmb
prraent. 1here were по рати plana exudates. FIuaresetin
angiography in the left eye was normal i.F). An е1ес:1гоге1-
iiiaryram was normal. The Ejpother presented al aije 2T years
compl^yjpftig of gradual Visual loss lor П years. He denied
nyctalopia or hemeralopia. FHis visual acuiLy was 20/60
bilaterally. There were minimal vitreous cells present bilater­
ally, mild uplrtilinal membrane c:-h-iin£$esr and a Ear^t! cenlral
cysl surrounded Ejy smaller cysts in ihe center bf llie macula
E)i laterally 1C and bb. 1Ь н е was no peripheral ret5nost hi,-
нis. An^jio^iaphv revealed a local window djj feU hyperfluo-
nescence t:enlrally in both eyes ! . The retinal vessels and
HFJ£ H^ppcaned nonv-nl. An elecLrortfinogram revealed some
reduction of rod and cone amplitudes.
f—L= This 63-year-old woman had bi fa Lera I foveomacu lar
schisis ;; and K'i and peripheral retinal schisis. Angiography
was ипгетагкатй L.!. Her family EiisLory was neyalive.
a family of probable autosomal -recess ively inherited
peripheral retinoschisis without foveal schisis.786
Localized or Segmental Forms of Retinitis
Pigmentosa
Autosom al-D om inant Peripheral Annular
Pigm ent D ystrophy (Autosom al-Dom inant
V iireoretinochoroidopathy, se e ADVIR.C p . 243
in Chapter 5)
Autosomal-do mi nan L peripheral annular pigment dys­
trophy is characterized by coarse hyperpigmentation and
hypopigmentation for 360n, with a sharp posterior border
at approximately the equator, superficial and deep punctate
yellowish-while opacities, retinal vascular attenuation, tran­
sudation and neovascularization cystoid macular edema-
choroidal atrophy vitreous degeneration, and cataract for!
m a tio n ^ "'01. it is a relative stable disease and, unlike reti­
nitis pigmentosa, is associated with minimal nyctalopia
and visual field loss. ERG responses are normal in younger
patients and moderately abnormal in older patients.
Flistopathologically the findings show some similarities to
that in retinilis pigmentosa. Unusual findings include mul-
lifoeal areas of Loss of retinal receptors and extensive prereti-
nal membrane formation with cellular debris and layers of
Mii Her cells. Ihere is no histopalhologic evidence lo suggest
a primary involvement of either (he vitreous or choroid in
the pathogenesis of this disorder.
Posterior Annular (Pericentral, Circinate >
Peripapillary) Pigm entary RetinaJ D ystrophy
A variety of names has been given Lo the development of a
ring of pigmentary atrophy with or without intrareLinal pig­
ment migraLion in a ringlike zone immediately surrounding
[he posterior pole (Figure З.бЗА-Н)/ ^ -' l>? Ihese patients
usually have normal visual acuity, lhe ERG typically is sub­
normal and may be extinguished. When this condition is
not associated with pigment migration into the retina, it
has been called circinate choroidal sclerosis/'"' Progression
in most patients appears to be Slow.™ 79 its mode of
inheritance i& probably most often autosomal-recessive.
Paravenous Retinochoroidal Atrophy
Patients with paravenous retinochoroidal atrophy many of
whom are asymptomatic and have normal visual function.,
shoi^ a striking pattern of sharply outlined zones of atro­
phy of the RPE that follow the course of the major retinal
wins (Figure 5.62G). flQ9'ilhese may extend posteriorly
and he confluent wilh zones of atrophy surrounding (he
optic disc. I'here is often migration of pigment into (he
retina to surround the relinal veins, lh e condition is bilat­
erally symmetric, in most patients Lhe optic nerve and the
caliber of the retinal vessels are normal. Some cases have
shcrtm evidence of narrowing of the retinal vessels; optic;
disc pallor,. and changes in the HPE in the macula and sub­
normal acuity. One boy seen in Miami had eccentrically
Located macular staphylomata (Mgure 5.62G)f Chen el al.
described biiateral macular colobomata associated with
pigmented paravenous atrophy.1^0Fluorescein angiography
outlines the areas of RHL atrophy and in some cases may
demonstrate evidence of atrophy of the choriocapillaris.
Aulofluorescence imaging shows decreased autoftuores-
cence corresponding to the area of atrophy surrounded by
a /.one of normal or iso fluorescence, outside which there is
a ring of increased autofluorescence.:iM- '['his appearance
is seen in a variety of dystrophies associated with photo­
receptor loss, including cone dystrophy; sector retinitis pig­
mentosa. and con e-rod dystrophy, lhe increased fundus
aulofluorescence, and therefore, excessive lipofuscin accu­
mulation in K P K cells, may result from an abnormally high
turnover of photoreceptor outer segments or impaired R P li
Lysosomal degradation of normal or altered phagocytesed
molecular subslraLes. This arc of increased fundus auto­
fluorescence in different retinal dystrophies migrates with
Lime as the area of involvement spreads.
Га ravenous retinochoroidal atrophy may occur in sib­
lings and in successive generations/'00-''1--"4-1 Some cases
of paravenous atrophy are probably acquired as the result
of inflammatory disease.'1’ 6:& Gass has seen one patient
who presented initially with a widespread perivenous
distribution of acute chorioretinitis that over a period of
several years progressed to severe typical serpiginous cho­
roiditis. lhe occurrence of paravenous atrophy bilater­
ally in one of two monozygotic twins is evidence that in
some patienls it may have a cause Linrelated to genetic
5.61 Non-X-linked macular schisis.
A —F: Thin ЬО-уелг-old wum iin had be№cHrretEed vision of
2Q/2.T vision in eai'h- Careful ijxamiriattoti of the fovea
showed faint yellow stippling o l lhe temporal lovea in each
eve I ha I did not capture w ell on lhe photoj^mpta. O pt if л I
coherence tomography showed only mild Ihickenin^; and
cjysts in the temporal macula: qf both eyes. The intervening
pillars w ere obliquely oriented in the ir a n ila and vertically
oriented in lhe temporal retina lA-D ). There was no fam­
ily history suggestive оГ retinoschisis. She was treated w ith
oral aceLazolamide for more lha:i 3 months with only mild
changes in the height of the s-сЪi-pjs cavilv in httlh eyes :t and
F . Shy m fiinclined a vjsion (if Лр/25 and the actHazcil amide
was stopped.
|Cu J r t « y tj[ L)r. t':+kV.ird t Ьетгмгу.)
makeup. Males are affected more than females, in about a
4:1 ratio.""' :,|Л Some cases are familial, most are sporadic;
no definite inheritance pattern has been established.01''"105
Mutations within the CRB1 gene have been found by vari­
ous groups; other conditions associated with C K iiJ muta­
tions include some cases of Leber’s congenital amaurosis,
early-onseL retinitis pigmentosa (РРДРЁ, HP 12), and reti­
nitis pigmentosa associated with Coals'-1i ke vasculopathy
Jt appears that loss oJ'C’WIif leads to displaced photorecep­
tors anti tocal degeneration of all neural layers attributable
lo loss of adhesion between photoreceptors and Muller
cells.
Hlectropbysiologic tests are usually normal or only
mildly affected but in some instances may be markedly
sufcmormaljй0HvHlW Most cases fail to show progression. In
some cases, however, the disease onay progress and result
in significant visual loss. In a sLudy of IF patients over
lime, the mean change in remaining visual field and ERfi
amplitudes was much slower than in patients wilh typical
retinitis pigmentosa.’"''
Differential diagnosis includes angioid streaks, helicoid
peripapillary chorioretinal degeneration, radial lattice reti­
nal degeneration, and chorioretinitis.
Sector Pigmentary Retinal Dystrophy
In some patients the ophthalmoscopic evidence of pig­
mentary retinal dystrophy that may or may not be asso­
ciated with hone spicule pigmentary migration may be
confined to one sector of the fundus, most frequently the
inferonasal quadrant (Figure 5.621 E and [he dis­
ease is usually discovered in adult patients who may have
mild symptoms of night blindness. 'Jhey usually show
slow progression of the disease, which rarely reaches the
disabling stage. Jhe visual acuity is usually normal, lletinal
arterioles in the area of pigmentary changes are narrowed,
lhe field defect usually corresponds wilh the area of К [3b£
atrophy. AbsoSute visual thresholds, hoitfevet may be ele-
vaLed Lhroughoul Lhe retina.f2&,a31 Occasionally chronic
angle closure glaucomar macular holes, and exudative vas-
culopaLhy have been associated with щви-835
 (uvenile nephronophthisis and sectoral retin lies pig­
mentosa have been associated in one instance."''
I listopathologic and metabolic abrtortHaffl^fe involving iht;
ш ш 1а1-арреаЩ ге11|Ё have also been demonstrated.
In patienls showing minima] ophthalmoscopic evidence
of RPt changes in lhe affected arear the field defects may
simulate a nerve fiber bundle defect or bitemporal hemi-
anopia and lead to the mistaken diagnosis of glaucoma or
an intracranial lesion."'’ 1' HlecUortlLnography may show evi­
dence of rod, rone, or combined dysf u n c t io n . 1-luorescein
angiography is helpful in detecting the sector areas of atro­
phy of the ft PL that may be overlooked ophthalmoscopi-
cally. Most cases are sporadic, but autosomal-recessive and
dominant inheritance Dociirs.3^"1^ 58-6-14 Jtod opsin muta­
tions are responsible Гог autosomal-dominant inheritance
of segmental retinitis pigmentosa in some families."'"
lhese latter patients demonstrate abnormal dark adaptation
kinetics nith marked prolongation of the later phase of rod
adaptation.141,1
Patients with sector pigmentary retinal dystrophy
should he clearly differentiated from patients wilh seg­
mental areas of bone spicule pigmentation related lo
long-standing serous detachment, such as occurs particu­
larly in some patients wilh a severe form of idiopathic
central serous chorioretinopathy {see Mgure .S.06) and in
patients with acute zonal occult outer relinopathy (see
Ngure 11. Ift}. In such cases the distribution of pigment ary
changes is usually asymmetric. Although sector pigmeti-
Lary retinal dystrophy may occasionally occur unilaterally,
pigmentary changes When confined to one eye are much
more likely Lo be the result of trauma [see Figures 8.Q2D-E-'
and S.03L); previous long-sLanding retinal detachment
related to a retinal hole, choroidal hemangioma (see
Figure 14.1GJ or choroidal nevus; or previous occlusion of
a large choroidal artery.
Unilateral Retinitis Pigmentosa
The diagnosis of unilateral retinitis pigmentosa should
he made only when: [ l j Lhere is functional efectroretino­
graphic and ophthalmoscopic evidence suggesting a pri­
mary pigmenLaiy degeneration in one eye; (2) Lhe visual
function, li-HG, and appearance of the other eye are nor­
mal; [3] follow-up has been at least 5 years in order to
rule out delayed involvement of the second eye; and (4)
inflammatory. traumaticr or olher causes in the affected
eye have been excluded. 14,1 Patients wilh these criteria
rarely have other affected family members, and their fun­
dus changes probably are caused by some acquired disease
rather than by a primary genetically determined dystro­
phy (Hgure 5.62J and K }.642,8^3 i:emale carriers of X-l inked
ret ini its pigmentosa can develop unilateral symptom­
atic retinitis pigmentosa when the process of lyonizalion
S .62 Locafized forms of pigmentary retinal dystrophy.
A—D: Annular pigm enlary retinal dystrophy in л 6-3-year-old
man com plaining of nyctalopia of lfl monlhs' dura! ion. His
family hislorv was negative. Visual acuity was 20/20 in lhe
right and 20/200 in lhe lelt eye. C olo r vision testing was
markedly abnormal. H is electroretinographic studies showed
moderalely abnormal nod and cone dysfunction. Note the
i:ng [)! retftlaJ pigjtfiEnl epi I helium alrophv surrounding lhe
macula (A—CJ. Angiography in the It^L eye ([>> shuwed e v i­
dence of a tainl bull's-eye pattern of hyper fluorescence ten-
Iralh- lanowsl. There lias been only minim al change in the
fundi and visual function during the ti voaTsof follow-up.
E and F: Identical I w in females developed mild visual loss
associated with foveomacular schisis in their Leenage years.
The schisis disappeared in their 20sr and they developed an
incomplete segmental annular dystrophy of the pigment epi­
thelium and id in n in iheir 30s It njnd Fl. Their visual acuily
VuaS 20/20 hi laterally. Eileclroretinogiaphy was within normal
I j m i I l-.
G : P’aravencnjs relinochoroidal aLrophy and m acular slaphy-
Fomata in a 34-year-old Latin boy whose visual acuity was
20‘25 in the righl eye and 20/200 in lhe lefL eye. His elec-
Lroretinogram showed severely abnorm al rod and cone
fu n d u M Hi к family hislorv was negative. A sjmiluT picture
was present in bolh eyes. This u -лл observed a1 age years
and photographs during the pas I 5 years have revealed only
minor changes in the fundus appearance.
H and I: tegmental neLfnitis pigmentosa involving lh e nasal
half of the lundi (H i in a -17-year-old man with a bitemporal
hemianopsia. A paternal nunl had rtaL5niIiн pigmentosa. Visual
acuily was 20/20, The lumpoml halves o f lhe fundi w ere nor­
mal fl). H is co n e and rod electroretinog^aphic findings were
moderately abnormal.
|-L: L-п i lalera I relinilis pigmentosa-like fundus in a 34-year-
old wom an w h o was asym plom atic before presenling w ilh
acute Loss ot central vision in Lhe right eye caused by a sub-
retanal neovascu lar membrane in lh e righL eye :arrow, J.. In
addition Lo lhth typicHj findings of pseudoxanthoma elasLi-
cum w ilh angioid streaks and peau d 'orange changes in bolh
eyes, she had marked narrow1ing of Lhe reiinal vessels and
extensive 360'' bone—corpuscular changes ihsl w ere con­
fined lo lhe left eye -Lj. An eleclroretinogram was normal
in thn righl eye and severely abnormal in the lefl eye. Visual
acuity was 20/30 right eye and 20/20 leJl eye.
inactivates the normal X chromosome, inflammation,
trauma, and cojnbined choroidal and retinal vascular
occlusion are probably responsible for most cases. Jn lhe
southeastern USA diffuse unilateral subacute neurorettni-
tis is the commonest cause of a unilateral retinitis pigmen­
tosa-] ike syndrome (see I'igure 30.2ft). Patients with acute
ional occult outer retinopathy and multifocal choroiditis
and panuveitis may also present with unilateral fundus
changes typical of relinilis pigmentosa [see Figures 11-Л8
and II .1?).
A T Y P IC A L P IG M E N T A R Y R ET IN A L
D Y S T R O P H IE S A S S O C IA T E D W IT H
M E T A B O L IC A N D N E U R O L O G IC
D IS O R D E R S
Gyrate Atrophy ot the Choroid
tliyrate atrophy of the choroid is а rare recessive!}' inherited
chorioretinal dystrophy and inborn error of metabolism
caused by a generalixed deficiency of the mitochondrial
matrix enzyme ornithine aminotransferase. Myopia and
nighL blindness are the first clinical symptoms and the
disease appears in. childhood. It is manifest early in life
as garland-shaped, sharply defined zones of chorioretinal
atrophy involving the mid periphery o f'the fundus (l-'igure
5.63A and ]"hese lesions spread peripherally and
posteriorly. The macula is usually invohred later in life.
Ixjcal areas of atrophy are variable in size and fuse to form
Earge atrophic areas wiLh festooned edges (Figure 5.63).
Ihe mechanism for the chorioretinal atrophy remains
unknown; ad4ierse effects of creatinine or deficiency of pyr-
rol'ine-B-carbojiilate on retinal function may be a cause361*
Small glittering crystals may he visible on the fine velvet­
like RE^Il in areas unaffected by choroidal atrophy. Some
pallor of the optic disc, vitreous opacities, narrowing of the
retina! vessels, and cataracts occur during the later stages of
the disease. Optic disc drusen and cystoid macular edema
miry occasionally Qccw.'qu-Ma 'L'he late fundus picture may
simulate that of advanced choroideremia (Figure 5.631
and J] or LGRM D, Most patients have a high degree of
myopia and manifest varying degrees of night blindness.
Progressive peripheral field loss accompanies the fundus
changes. N' Color vision is normal UEilil later Eife. The LO G
is markedly abnormal. Ihe scotopic E^RG is usually extin­
guished. lioth rod and cone amplitudes may be severely
reduced in early childhood at a time when the fundus
changes may be m inim al." Dark adaptation reveals pro­
gressive loss of nod function. lakki64 л and McCollough
and have demonstrated abnormal levels of
ornithine in the plasma, urine, cerebrospinal fluid, and
aqueous humor in these patients. The enzyme ornithine
ketoacid transaminase is deficient in these patients.4'1'
At least 50 different mutations have been found in the
OAT gene mapped lo 10^2(3.^"" Nearly half the patients
that are known are of Finnish origin, in addition lo the
eye changes, other systemic findings include: ( I) minor
decreases in intelligence; ( 2} changes in the electro­
encephalogram (EEC ); [3] minor weakness of muscle;
(4) changes in staining of type IE muscle fibers; (5) Lubu-
lar inclusions in muscle cells on electron microscopy; f6)
fine, sparse, straight hair with microstructural changes;
and (7) lenglhening and enlargement of mitochondria
in liver cells.1^"'5*'1 ihe central nervous system involve­
ment in patients with gyrate atrophy and hyperornithin­
emia involves degenerative changes in the white mailer in
approximately 30% of patients with gyrate atrophy and
S.63 Gyrate atrophy of Ihe choroid.
A —C : Gyrale atrophy in a 25-year-old wom an whose visual
acuity was ri^ht eye and 2(>/£J0 left eye. The rod and
to n e eEectroretina^ram was- extinguished. H e r serum urni-
ihine lev-ul was 7 5 J |nnol,'L.
1)-L: A 43-year-old motEier com plained of nyctalopia for
2 years. She Larried a diagnosis o f KetinitEs pigmentosa for
30 уе^гн. f t p visual acuilv Was 2 0/20 Eialh eyes. W ide-field
pholngrapEis show peripheral p>igmenl change ir> a reticular
Of Jishnet-fEke pattern w ith norma l-ca liE>er vessels ID -G j. Her
ringiog^an-j showed liypoflJOresi^tlCe corresponding to the
pigment with adjacent areas of hyperfluoresicfcince I HI. Her
two affsfcted sens With progress-i ve jjaiL dislurtiance showed
periphery] h tim m jl^ thorm relinnl atrophy that was sym ­
metric: between the 1viO eyes and Eietween each (jlher Lypi-
cal ol gyrate atrophy ll and J). The atrophic patches were
hypoautoflLiorescenE w ilh intervening areas o f increased
riuLniiuorescence iK- in her and her non s. O ptical coher­
e n t tomography showed preservation (Я rt'linal pignienl
epitheliLim and pholcreceplurs in ihe intervening лгчмн hul
loss cprrespondrrtB to the atrophic Stines :L I. The angiogram
showed loss of <.l>ori oca pil laris in I hose areas.
ilJ - L , :l i i j г I -i,' u l l > r . LJ-.iv icl Ь л п л Г
70% ol' patients have premature atrophic changes, a strik­
ing increase in the Virchow's spaces. About half the patients
show abnormal background activity on FIX'.. Ihe KLС and
MR] findings do not correlate wilh each other.
ihe re are two clinical subtypes of gyrate atrophy based
on the presence or absence of an In vivo response to vita­
min Uf|J which is ihe cofaclor of the enzyme ornithine
aminotransferase. Vitamin H(, responsiveness is defined as
а БС№о reduction in serum ornithine levels. Patients with
B 6 responsiveness generally have a milder disease than
ihose who are not responsive. Somalic celt hybridisation
studies have demonstrated absence of complementation
among K,, responders and non responders, which indicates
that these iwo forms of gyrate atrophy probably represent
different allelic mutants of the same gene.:" i "’' 1 Lise of
arginine-restricted diel has also been shoxvn to slow pro­
gression of the vision Loss in patients with gyrate atrophy
due to lower plasma ornithine levels. Carriers of gyrate
atrophy have no clinical signs but in ay have slighl eleva­
tion of blood ornithine levels, clear ornithine more slowly
on loading test, and demonstrate only 50% enzyme activ­
ity on cell culture. Mutations of the ornithine aminotrans­
ferase gene show a high degree of heterogeneity, reflecting
the heterogeneity of the disease.1"5'1'*"1!!7r
Histopathologic examination of eyes of a patient with
Vitamin J^.-responsive gyrate atrophy has shown abrupl
transition between normal retina and near-total atrophy of
ihe retina, pigment epithelium, and choroid correspond­
ing with the gyrate areas of atrophy seen clinically.1" "
Mitochondrial abnormalities may be evident in the cor­
neal epithelium, nonpigmenled ciliary epithelium, and lo
a lesser exlent in the photoreceptors." 6
 ibe differential diagnosis of gyrate atrophy includes
choroideremia and generalized choroidal sclerosis.' J ''
Peripheral confluent zones of old in active chorioretini­
tis secondary to congenital or secondary7syphilis or other
inflammatory disease if discovered in young patients
might be cor]fused wilh gyrate atrophy. Similar multiple
geographic zones of atrophy also occur after spontaneous
resolution of large zones of suh-RPE large-celI lymphoma.
(See Chapter 13. p. ll&CJ.J NFKCD, IJothnia dystrophy,
and 1.0 RML) are other conditions that have Earge areas of
geographic atrophy in the midperiphery that progress over
time.
Blood ornithine levels have been successfully lowered
through the therapeutic use of vitamin b^ 3-86***'77 pypj.
dosal phosphate,? and a iow-arginine diet.r ii; : " The
results of therapeutic trials lo date are inconclusive as lo
whether treatment is of benefit in retarding progression of
the d isease.8* ’■
Ч
Hooft's Syndrome
i looft's syndrome is an autosomal-recessive disorder of
tryptophan metabolism, characterized by atypical pig­
mentary retinal dystrophy, extinguished ERG, panhypo-
lipidemia., hypoglycemia, mental and growth retardation,
erythematous skin rash involving the face and extremi­
ties, whitish discoloration of lhe nails* dry hair, tooth
decay, and a progressive course leading to death by 2 years
of age." lhe fundus may show a dusty-gray appear­
ance with pigmented spots or gray or yellow patches,
lhe macula has been described as appearing to be 'cov­
ered by a kind of snail's s itin g ™0'['his is a varianl of the
llassen-Kornxweig syndrome but without steatorrhea and
acanthocylosis.
Cystinosis
Nephropathic cystinosis is an autosomal-recessive Iу inher­
ited storage disorder in which non prole in cystine accu­
mulates with ill cellular Jysosomes caused by a defect in
lysosomal cystine transport, liarly in life these patients
experience growth retardation, renal tubular and glomer­
ular dysfunction, anemia, and hyperthyroidism. Renal
transplantation is usually necessary by 10 wars of age.
Ocular manifestations usually develop in the fLrst year of
life and include photophobia; progressive accumulation
of coruealr conjunctival, and iris crystals; and yellowish
mottling of the pigment epithelium in the macula and
more marked mottled REnti degenerative changes in the
peripheral fundi (figure 5.<S4Aand В),йм'ш crys­
tal deposition begins in the superficial peripheral comeal
stroma and subsequently involves the central and deeper
i.64 Cystinosis,
Д and B: There was л peculiar yellow crystalline material at
Lhe level of lhe uHtsroi d anti relinal pi^menl epi I helium in л
7-year-old gjH w ith renal insufficiency diagnosed as cystine
догаде disease.
(. : Л 14 -year-old Femd]c with cyslinosis developed a urinary
Lract infection a I b months of aj^e. ih e w as dja^nosed as hav­
ing R in co n i s hyndrome. A1 6 year*. she developed pholo-
phohia and multiple corneai crystals w ere noted. At 7 years,
bright refraclile deposits were noled in lh e choroid. Visual
acuilv was normal. ih ch died a I 14 years or ,ige ffom com pli­
ca! ions ol im m unosUppreSartl therapy following renal trans­
plantation. Histopathologic examination of the Eyes revealed
square, rectangular, and sliverlike crystals in the choroid.
These crystals w ere also found in the cornea, iris, ciliary
body, sclera, episclera, and optic nerve shealh.
IА, Ггопн h l l t t i ,:l.yl|: A|-ntrirj,>n M ed ical A ijd eijn ln rk A ll
ri^Fili Reserved. fruro ' ■
corneal stroma. Fine crystals may be visible in the retina
in some patients/ 11^ 1p‘" With longer survival made
possible by renal transplantation, additional ocular com­
plications have occurred/1’' 'lltese include incapacitat­
ing photophobia, blepharospasm, posterior synechiae,
thickened iris stroma, crystal deposition on the anterior
lens surface, tritan color vision abnormalities, elevated
dark adaptation thresholds, reduction in rod and cone
amplitudes elect roretinograp hie ally and impairment in
visual function. 'Ibere is some evidence that cystinosis in
the Krench Canadian population may be associated with
milder complications of the disease.H istop atho logic
and ultraslnictural examinations have shown evidence of
intracellular crystals within the RFE and choroid but not
in the retina fig u re 5.64C). Ef is probable that accumu­
lation of cystine crystals within the RE’Ei is responsible for
the characteristic fundus pictures seen in these patients/"''^
although Winter found the crystals only in the choroidHi,'J
(figure 5.64С].
Cellular cystine accumulation, which is the putative
cause of the ocular damage, can be reduced by over 90%
wilh the free thiol, cysleamine, both in vitro and in vivo,
'ibis treatment apparently stabilizes renal function but
does not reverse exisLing renal damage. Likewise, it does
not reverse the corneal deposition of crystals and proba­
bly does not reverse the retinal dysfunction.' '1 Studies are
needed to determine whether cysteamine therapy, which
is usually discontinued after successful renal transplanta­
tion, is of benefit in retarding progressive ocular changes.
Cysteamine eye drops have been used to reverse corneal
crystal deposition. '1''
Albinism
Albinism is a group of disorders associated with an inborn
error of amino acid metabolism affecting lhe production
of melanin. Associated defects that may occur include
nystagmus; strabismus; large refractive errors* particularly
myopic and astigmatic errors; macular dysplasia (hypo­
plasia); deafness; mental retardation; reticuloendothelial
incompetence; and coagulation d e f e c t s . Macular
dysplasia is characterized by loss of Lhe foveal depres­
sion and reflex and absence of or ill-defined capillary-free
/one (Pigure 5.65СГ Eir Fr and EHJ. bonne paLients, however,
demonstrate a capillary-free zone by fluorescein angi­
ography.'11"1 Prominent retinal blood vessels may course
directly through, rather Lhan arching around, the dysplas-
tic macula (figure 5.65
Oculocutaneous Albinism
Oculocutaneous albinism may be inherited as either an
autosomal-recessive or a dominant trail (figure 5.65A-
:i Most patienls with ophthalmic symptoms
have the recessive form of the disease. Patients whose hair
bulbs lack tyrosinase have platinum blonde hair, pink
skin, severe photophobia, nystagmus, subnormal acu­
ity, diaphanous, I ighl-colored irides that transilluminale
diffusely (Pigure .3.65И), absence of pigmental ion of the
fundi, and macular dysplasia. Patients wilh tyrosinase
in the hair bulbs usually have more ocular pigmentation
and less visual symptoms and disability. Three subtypes
of tyrosine-negative oculocutaneous albinism include:
( ] ) tyrosinase-negative albinism; [ 2} platinum albi­
nism; and (3) (he yellow mutant type, tight subtypes of
tyrosinase-positive oculocutaneous albinism include: ( I )
minimal pigmenl oculocutaneous albinism, ( 2] tyrosi­
nase-positive albinism; [3] brown albinism; [^) minimal
pigment albinism: (5) Herman sky-Pud! ak syndrome; (ti)
Chediak-Uigashi syndrome; \7) rufous albinism; and (a)
autosomal-dominant albinism : Other features of
Chediak-ltigashi syndrome include: reticuloendothelial
incompetence associated with susceptibility to infection
and lymphomatous disease, lymphadenopalhy, hepalo-
splenomegaly mental reLardalion, cytoplasmic inclusions
in leukocytes, and death in childhood (E:igure 5.G5K and
l.).:' JI Features accompanying oculocutaneous albinism
in Hermansky-Pudlak syndrome include: blood-clotting
defecl (caused by defective glutathione peroxidase activity)
and Cross's syndrome ( microphthalmos, cloudy vascular­
ized corneas, skeletal anomalies, athetosis, and mental
retardation}.14'
O cular A lbinism
P a tie n ts with a defecl in melanogenesis that is la rg e ly
confined lo the eye fail into three major categories:
( ] } Lhe Netlleship- Tails X-finked type ( t h e most com­
mon of the three c a t e g o r i e s 4 ( 2) the
l-'orsius-trtksson X-Linked type [ A l a n d Island disease),
S.6i Albinism.
A—C : О си loc uLa nE*ous albinism in a 16-year-old girl w ilh
lull Lranurikirv.inaLicjTi of the indes. S f e had nystagmus; Visual
acuily was 5/20Q. Her pa luma J ^randhalhei and l*is brolhers
had albinism. Therfe wab no well-defined cap(l|&ry-free zone
nr foveolar depression a q liiic № c D illc a l ly it".
D - F : O t UI Of uLl ПC4JUS ■I I ■!!1i ^П I. O jjlic ПОГУе I IVpOpI a i J a , a n d
flj&ked relina in п 127-year-old LaLin man with nysta^mUj^
poor vision, and mild hyperOpic asIijjfiialism all a t bib life.
The mother, and piiternal yrandlalbLT w uts blond but find
good vision
С —г X-linked ocular albinisni in а 14-year-old man w ilb
nyhLaymuh and 2CV70 acuity. Hu had dark hiair, hncnvn irides
LhaL showed scmt' Lransil Ilitti i пл Li езл defects,, aijtfl albinoLif
kind: With fovea I dysplasia.
j: SLrcaky and mol I kid rut i: id I pi|^ncml epi I helium in an
asymptomatic female carrier of X-linkud ocular albinism.
K: O culocutaneous albinism in Chediak-Hi^ashi disease.
L: Stlppllhg of w hile cells in Г hudiak-l-Ei^ashi syndrome.
accompanied by an atypical protanomalous defect (E'igure
5.65C-1 ]''' and (3J the autosomal-recessive type. Alt have
impaired visual acuity, translucent irides, congenital nys­
tagmus. photophobia, hypopigmentalion of the fundi,
and macular dysplasia. Some of lhe female carriers of
the Nettleship-Palls type show patchy areas of iris trans­
it! Limination and a coarsely mottled or irregular streaky
change in lhe RP£ peripherally (E'igure 5 .6 SJJ,The affecLed
patients and obligate carriers have abnormal giant mela-
nosomes in the skin.d!t5,i,97-Mfi rrhe pigmentary mosaicism
in carriers is not found in the horsius-txiksson type.
in a variant of X-linked ocular albinism in black males
there may be a lack of iris transillu mi nation defects and
characteristic fundus hypopigmenlation.'''''1 Lhe visual acu-
ily is belter than in typical X-l inked ocular albinism and
diagnosis may require skin biopsy '1Ъе carriers in addi­
tion to having the typical fundus changes, may have a
striking alternating spokewheel-libe pattern of the iris stro­
mal hypo- and ftyperpi|gmentBii|1d>ft^15
i iislopathologjc examination has revealed evidence of
foveomacular dysplasia, including absence of the foveal
pit in palients wilh oculocutaneous as welt as ocular
albinism.'1^ [tie ganglion cell layer is present
throughout the macula, and the cones resemble those seeti
in the normal parafoveal area.
Variable results have been reported in regard lo 1Ж т
findings in patients with albinism. Whereas some have
suggested that increased a-wave amplitudes and shorter
latencies of both a- and b-waves are characteristic of
patients with ocular as well as oculocutaneous albinism,
others have reported that most of these patients have nor­
mal DIC. findings.'^1'P a t ie n t s with ocular albinism
should be distinguished from palients with isolated foveo-
macular dysplasia and Lhese wilh dysplasia associated
With aniridia.'" "JJ Flash visual evoked potentials acid
1-KC may he helpful in this regard.'' "
%
Partial O cular A lbinism
Congenital heterochromia of the iris and fundus may
occur alin e (Figure 5.6(Ю-|) or may be associated with
Localized congenital depigmenlation of lhe лkin and
hair, Гог example, Waardenhurg's syndrome (Figure
5&GA
Primary Hereditary Hyperoxaluria
Primary hereditary hyperoxaluria is a rare in bom error
of gty ab late metabolism characterized by calcium oxa­
late nephrolithiasis, chronic renal failure, and systemic
deposition of oxaEate crystals in many tissues, including
the tie art. bone, testes, central nervous system, thyroid,
media of arteries, adipose tissuer lymph nodes, muscle;;,
skin, and eye.': j , -":" Approximately 30% of patients will
demonstrate rettnopalhy.^-11 '['here are two types of hered­
itary oxaluria. 'I'ype ! hyperoxaluria results from defi­
ciency of the cytoplasmic enzyme hepatic peroxisomal
aIani ne :glya >1ate am inotrisnsferase." :■■": 1 Itiese pat ienls
have increased urinary excretion ol' oxalate and glycolate.
Type 11 hyperoxaluria is caused by a deficiency of г^glyceric
dehydrogenase, which causes an increased synthesis of
oxalate. Only patients wilh type ! are symptomatic and
develop eye signs. I'hese include crystalline flecks Widely
scattered throughout ali layers of the retina and ЙРЕ
[E'igure 5.67). Irregular dense clumps of RE4\ hyperplasia
and hypertrophy, and fibrous metaplasia, ranging in size
from small ringlets I о large several disc diameter-si^e geo­
graphic plaques, occur in the macula r area.'1-1 'n i-J ' ‘Optic
atrophy as well as choroidal neovascularization may occur.
Visual acuity loss is greater in those patients with optic
ateophiy,531^-1
In type [ primary hyperoxaluria, the calcium oxalate
crystals early in life may be deposited primarily in (he
ftp И at the posterior pole.1'1'1 En older children, however,
the crystals clinically and histopatbiologically are found in
great numbers in the retina With a tendency for periarte­
rial distribution.0-1, EJypertrophv and hyperplasia of the
ftPE are prominent in the macular area (figure !>.G7A and
in a 46-year-old man with a clinically milder and
Liter-mi set :.imili.:.l Ьурсгоха-ипл, ophlhalmoscopicallv
and hislopathologieally the crystals were located primarily
in the outer plexiform and nuclear layers of llie retina and
not in the pigment epithelium and inner retinal layers.'" 1
HistopaLhologically, oxalate crystals may be found in the
otber ocular and body tissues, including the kidneys.4-'1
Sim ilar retinopathy has been described in acquired oxa­
losis following meLhoxyflurane anesthesia that produced
acute renal failure (see Hgure 9.09G-K).'J ' ■'4 'i A similar
retinopathy has been produced in rabbits by injecting cal­
cium oxalate subcutaneously.'JJe .lhe differential diagno­
sis includes the fleck retina syndromes, jBietffs crystalline
dystrophy, cystinosis, gyrate atrophy. Sjogren-l.arsson syn­
drome. tm exifen reLinopathy, Alport's syndrome. and talc
i . f Partial albinism.
A - C : Rirlial albinism in W^arcfGnburg's syndnorjfe jn this
13-year-oEd black ^irl with partial deafness,, white forelock,
synophrys, lateral displacement o f fhe medial CEinlhus, and
jTeterochtritflia of (he Uides and fundi. H e r v iнил!! acuity in
the rijjht eye was 20/25 and in the left eye was 20/40. She
did nol have poliosis of lhe eyelashes and brGw or congeni­
tal vitilijjo of lhe кк1п. The left iris {A) and fundus |Cl were
hypopa^mynted.
D - G : This 20-year-ald Latin male with visual acuity o f 2 0 /2 0
bilaterally had heterochromia of the irides and fundi ID and
Ё , some I os-я of hearing in lhe ri^bl ear. pBthiS m cavatum
11-., and a low cato-au-lait ipots Lt-i'. Hih parents w ere cous­
ins. The familv hiilory was fie^alive for ocular nEinormalititfs.
H —|: Heterochrom ia ol the iris I'Hj and fundi (l> in а 6-year-
dd black Ejov w ilh visual a-LLiilv in btrth eyes.
1. СгDmthumpsun und Curtllt’ f^ KJ 1994. Amerit/ил iVtediLnl
IL>—
A m ih . i. iI i№ l Л И r:^ .h L b, j t i c r w d . '
embolization, '['he progressive BPE changes that may occur
in association with oxalate crystal s. may simulate any of
the disorders associated With atypical retinitis pigmentosa.
Inborn Error of Vitamin B 12 Metabolism
Ibere are at least three autosomal-recessive inborn errors
of intracellular cohalamin that may cause methylmalonic
aciduria wilh homocystinuria. lhe cohalamin form
may be caused by deficiency of a cytoplasmic hydroxy-
cohalamin reductase that results in faulty synthesis of the
two active forms of cohalamin and absence of adenosyl-
cobalamin and metbylcobalamin. Absence of these lat­
ter two cofactors results in methylmalonic acidemia and
aciduria, accumulation of homocysteine and its deriva-
livesr and decreased methionine, liarly in life, patients
wilh the cohalamin С type of melhyl т а Ionic aciduria and
homocysLinuria develop failure to thrive, developmen­
tal delay, seizures, megaloblastic anemia, and a progres­
sive maculopathy.'..... 11 Exported ocular findings include
pigment epithelial mottling in the macula with progres­
sion lo a bull's-eye ap p earan ce,p erip h eral satl-and-
pepper pigment changes,'4" and oplic disc pallor.'^ Most
patients develop nystagmus early in life, but its onset may­
be delayed in some patients. Visual acuity is reduced lo
20^200 or worse in most patients. Pupillary response may­
be sluggish. Hyelid clonus may be evident.940The electro-
retinographic amplitudes are reduced early, lhe cones may
be more affected than the rods.'M‘
] Eislopalhologic and ultrastruclural examination of the
eyes of a 22-month-old chEld revealed depigmentation of
the rtPEi and loss of receplor cells in the macula, reduced
numbers of (he small ganglion cells in lhe papillomacular
bundle area, thickening of the posterior sclera associated
wilh accumulation of acidic and weakly sulfa ted muco­
polysaccharide, and diffuse storage of material in clear or
granular cytoplasm in most of the ocular tissues.14,1
Methylmalonic Acid Urea Cobalamin-C
Type
Methylmalonic acid urea wilh homocysteinuria cobala-
min-C type is [lie commonest inborn error of vitamin K. i
metabolism. It is an auLosomal-iecessive disorder caused by
mutation in the MMACH& gene. Early- and late-onset sub­
groups are distinguished based on their age of onseL.'*'1^ ),|(r
Patients who present within the first year of life are affecLed
more severely than ihose with Liter onset. Ihe early-onset
group of patients presents wilh failure to ill rive, lethargy
anil feeding difficulties, 'these child ren show neurologi­
cal deterioration, multisystem pathology pancytopenia,
megaloblastic anemia, cognitive disabilities, and progres­
sive retinopathy. Ihe ]ate-onset group presents with gait
abnormalities, extrapyramid aI symptoms, psychiatric distur­
bances, dementia, mild to moderate cognitive disability, but
no retinopathy. Jiarly recognition of the condition and treat­
ment with hydroKycobalamin. vitamin supplementation,
carnitine and Ji.:. help to modify the Severity of the disease.
The ocular findings have shown progressive macular
changes which initially appear to be a bull's-eye macu-
lopathy which continues to progress with central atrophy
and hyperpigmentation (]:jgure 5.67tj and 11). Coarse pig­
mentary retinopathy with bone spicule formation is seen
over time (figure 3.4371 Consecutive optic atrophy
occurs subsequently '['hose patients with late-onset dis­
ease show reasonably got>d оси tar function, including rod
and cone-media ted ERG responses. No significant ocular
pathology has been noted. Subtle ERG or l!OG changes
may not be functionally significant."'1'' ''i0
Vitamin Л and t Deficiency
Combined deficiency of vitamins A and fc may cause nyc­
talopia and progressive retinal degeneration in humans/'1"
IJergeretal. reported these same changes in a patient with
an lfi-year history of avitaminosis E associated with an
autosomai-recessive form of intrahepatic cholestasis with
malabsorption of predominantly vitamin Ei?™ ]hey sug­
gest that the vitamin fc deficiency may be the major cause
of the retinal degeneration previously attributed to com­
bined deficiency of vitamins A and b..
R ET IN A L C IU O P A T H IE S
disruption of the function of proteins associated with
photoreceptor cilia results in л wide variety of phenotypes
ranging from isolated retinal degenera Lion to more wide­
spread phenolypes. Systemic associations include neuro-
sensory hearing loss, developmental delay, situs inversus,
infertility, disorders of limb and digit development, obe­
sity, and kidney, liver, and respiratory disease. Ih e retinal
dliopathies include retinitis pigmentosa, macular degen­
eration, cone dystrophy, cone-rod dystrophy, l.eber's con­
genital amaurosis, retina! degenerations associated with
Usher syndrome, primary ciliary dyskinesia, SertJor-Jtikeri
5.67 Vrim ary hype roxa Iuria.
A *n d B: This 1-t-year-old female was referred for evaluation
oi black m acular Eesrons. Ac 9 years of age her visual acuity
was .20/20. Al 13 years, she had а rena] Iransplant Ьссьшке
of shrunken calcified kidneys. Her visual acuity al the lime
ol" these phonographs was 2 (V M . M<;ny ysllow crysH^B w w e
scattered Ihrou^houl ihe retina at dll levels. Note I heir pre-
dj led ion for periarterial distribulion. Irreyular gc*ogTaphit
blade subrelinal lesions WHh Incun не and stinic fibrous tissue
were presen I in the macula r агедо Уhe subsequently diud,
find Lhe histopalbolo^ic findings were similar to chose found
in secondary oxalosis (s№ Figure 9.09>.
F: primary fam ilial hyperoxaluria in a 33-year-old Irani a n
wom an w h o developed nephrolithiasis at 20 уеагг erf age.
Renal dialysis was necessary at age JO years. At that time
she had peripheral neuropathy, hyperuricemia, pericarditis,
and migratory1 arthritis. O n e brother had а тепл I transplant.
Four other relatives had renal stones. Visual acuity was 20/25
in Ihe right eye and JtV iO in Ihe lc*fL eye. Ih e limdi sliowrsd
widespread retinal crysLals and grade J hypertensive reLi-
nupalhy and 1.1). Angiography revealed marked loss p i the
peripheral retinal vessels (F) and eKtensive retinal vascular
chnmgei (t).
Methylmalonic actdurfa
G Гсэ I: This lti year old m^le with CF vision aL 1 feet in
e-ath eye, was bom al full term hy emergency C-sedion for
felal dislness. Al a|^e 6 weeks, he was found lo feed poorly,
was lethargic, irriLable, had emesis and poor muscle tone.
MlfethylnliJonic a d ri was Eound in his urine, fundns was nor­
mal at Iha I time. Vitamin ЕЛ2 shots were given with reduc­
tion in M M A. M ethylm alonic aciduria, cohalam in С type
(cbl-CJl was diagnosed. Al 9 monlhs of age he had nyslag-
tnUs, a "bulls eye maculopathy'' Was noted bi I ale rally and
Eh?С was non recordable. He received orientation and
mobility training, learnt BrailTe in kindergarten, has aver­
age 3CJ, gTaduatud hiyh school with peers and aLtends com ­
munity college. H e skis in the blind program and aspires lo
tjpfiome a sfjorls radio and T V slalihCician. IJolh m acula show
central chorion:1inal atrophy surrouffaed by hyperpijftnented
RFE. (G and HI. The rest of the fundus shows diffuse pigmen­
tary alteration w ilh coarse K PE clum ps and bone spicules Ш.
There was m ild w axy pallor o f the optic discs in both eyes.
IA .inrl b. Irun> Mcri.'Llilh d ,lI ,a-- „ i ■И М , A m m ил n I i:l .i I
Aisrjcia.iwjr'i A I rdi;l]ls nuurvit'cL C-f, CLKiilL'b-y uf 3>r. Kidi.m l A.
( I Lrj I. lhjurTL i'r' ('I Ur. A lin Kimuni.l
syntlrome. Joiifeeri syndrome, Elardel-tiiedl syndrome.
Laurence-Moon syndrome. Me Kusick-Kaufman s\rn-
drome, and Biemoni! syndrome. Mutations for these dis­
orders have been found in retinitis pigmentosa-1 (A P J),
retinitis pigmenLosa GTl:ase regulator retinitis ptg-
menLosa CJfl>ase regulator-interacting protein (RTGR-1P),
and in the Usher, Bardet-Biedl, and nephronophthisis
genes. Sj'stemic disorders associated with retinal degenera­
tions that may also involve ciliary abnormalities include:
Alstrom. ^d^'ards-Sethi, rllis-van Creveld. Jeune- Meckel-
G ruber, orofaciodigital type and Си trie гё syndromes.
Understanding these conditions as "ciliopathies''' may help
the clinician to recogni/e associations between seemingly
unrelated diseases and have a high degree of suspicion that
a systemic feature may be present.'bL
BARDET-ESIEDL S Y N D R O M E
IJardet-JJiedl syndrome is characterized by: ( I ) pigmen­
tary retinal dystrophy; ( 2) mental retardation; [3} congeni-
La] obesity (usually a J:nohlich. type); [4J hypogenitalism
(more frequently in males); and ( 5-1 polydactyly or syn­
dactyly (J:igure 5.6S].'J '' ' " ' i n any one patient, the syn­
drome may be incomplete. Other defects include deafness...
nystagmus, strabismus, shortness of stature, genu valgum,
pes plana, congenital heart disease, cystic kidney dysplasia.,
and atrophic pyelonephritis. Jt occurs more coinmonly in
males. '['he fundus often shows the typical changes of reti­
nitis pigmentosa and may in addition show evidence of a
bull's-eye maculopathy (figure [i.GtiA)."'1, Retinal wrinkling
caused by an epireLinal membrane may be present,?56'M1
KEuorescein angiography sboxvs evidence of hyperfluo­
rescence in areas of RPE atrophy and frequently shows
Eeaka^e of dye from the capillaries on (he optic nerve head
and paramacular area without evidence of cystoid macu-
Ear edema [E'igure 5.6SK-D).' lhe 1LKC iis markedly
abnormal or extinguished. Patients with no measurable
peripheral visual field may show a variety of different pat­
terns of central visual dysfunction: an island of only cone
function centered in a bull's-eye lesion, patches of rod func­
tion surrounding geographic atrophy, or a central island
of excellent nod sensitivity but severely impaired cone
function.®*3 The EOG is markedly abnormal,'ш Whereas
most patients retain central vision through their early
school yeans, many develop macular changes and 20/20(1
visual acuily or less during the second decade of life.™
Approximately 50% are legally blind beyond 20 years
of age. Most patients eventually become virtually blind.
The disease is inherited as an autosomal-recessive trait.
Premature death is often caused by renal failure secondary
to low-grade vesicourethral reflux, urinary tract infection,
and hypcrLensive vascular disease.""'' Jhere is an increased
incidence of diabetes meliitus in these patients.'"':
LAU REN CE-M O O N SYN D RO M E
Patients wilh Laurence-.Moon syndrome are similar Lo
those with Bardet-Eiiedl syndrome except polydactyly
and obesity are not present, and these patients develop
spastic paraparesis.":'! E'urlherr these patients show
extensive choroidal atrophy approaching that seen in cbo-
roideremia. Some patients may show features of both syn­
dromes.™ A hypothalamic hamartoma was found in one
patient. ■jt.:
A LSTRO M SYN D RO M E
Patients with Alslrom syndrome [Alstram-] lallgren syn­
drome) manifest a tapetoretinal degeneration [infantile
SL6fl Bardet-Biedl syndrome,
A - 11: This 12-учзлr-old fiiFri w ilh men I л I relciidation, Hrohiich-
type obesity, polydactyly. night blindness, and a negative
family hislorv had visual acuily of 20/100. 1here w enj many
vilnjous tells. Her BlectfOreti rragt^rfji showed severely Jihnor-
mal rod and cone ninctioii, Note (.he narrowing of lhe retinal
arierfoles (A). Fluorescein angiography 1B-D) showed e v i­
dence of diffuse m;l I piym enlary changes лп-d ie.ikn^e of dye
from I lie retinal capiliaries- along the major B re a d s .
E a rd F: Frtihiich-Lype oIjtsiLy and polydactyly 'a rro w I in
anotfier paLienL with I b e r im e syndrome!.
retinal dystrophy} in association with obesity, diabetes
meliitus, acanthosis nigricans, polycystic ovaries, hypo­
gonadism, cardiomyopathy, and neurosensoiy deaf­
ness. '" :i Other features occasionally presented include
mental deficiency, baldness, hepatic dysfunction, and
hypertriglyceridemia.'1-,u-‘'1; Kenal dysfunction is vari­
able, age-related, and probably the most frequent cause of
death.'1'■They present with nystagmus and photophobia,
with severe cone dysfunction in infancy, progressive Eoss
of rod function, and usually an extinguished I:KG by 5
years of age and no ligbL perception by age 20.4 7 b'l hese
patients may be initially misdiagnosed as achromotopsia.
Handel-Kiedl, Leber’s congenital amaurosis, or cone-rod
dystrophy, infantile cardiomyopathy and/or weight above
the УOth percentile associated with severe early-onsel
cone-rod dystrophy should =ilert one towards the diagno­
sis.’1 : The condition is recessive Iу inherited and the defec­
tive gene ALAJS] maps Lo chromosome 2pI3. ihe ALM SJ
gene encodes a protein found primarily in the cettlro-
somes and basal bodies of ciliated cells, suggesting a func­
tion in cilia formation, maintenance, and funetion.'J'4,
JU V E N IL E F A M IL IA L
N E P H R O P H T H IS IS A S S O C IA T E D
W IT H T A P E T O R E T IN A L
D E G E N E R A T IO N (S E N IO R - L O K E N
S Y N D R O M E )__________________________
Some patients with aulosumal-reeessively inherited juve­
nile familial nephrophthisis or cystic disease of the renal
medulla may have an associated tapetoretinal degen­
eration.'1 :" '4: Jhe earliest signs of the renal disorder are
polydipsia, polyuria, and nocturia secondary lo impaired
urinary concentrating abilitv. The renal disease is insidi­
ous; there is little warning before development of uremia
or anemia. Results of urinalysis are essenlialEy normal.
Jhe retinal degeneration resembles leber's amaurosis, pig­
mentary retinal degeneration, and HPA. Usher's syndrome,
segmental retinitis pigmentosa, and Coats'1syndrome have
been reported in these patients.'4"'
JE U N E S Y N D R O M E
] liLs is ап autosomal-recessive disorder characterized
by skeletal abnormalities (short-limbed structure,, short
ribs), long thorax with respiratoiy insufficient.' that may
lead lo infantile death, brachydactyty, hjetaphysedl irregu-
Earilv, polydactyly, progressive rettali disease, occasional
ocular nibnorma Lities... Lnc Iuding reduced visual acuity,
photophobia, nystagmus, strabismus, and abnormal
LRG.4'" Histopathologic exa mi nation and electron
microscopy show mildly altered RPB, marked loss of reti­
nal receptor cells with relative sparing of cones, and mod­
erate loss of peripheral ganglion cells.''9
A R T E R IO H E P A T IC D Y S P L A S IA
(A L A G IL L E 'S S Y N D R O M E )____________
Alagl lie's syndrome is an autosomal-dominantly inherited
syndrome characterized by intrahepatic biliary hypoplasia,
neonatal jaundice, pruritus, cardiovascular anomalies (par­
ticularly pulmonary artery stenosis), vertebral anomalies,
growth retardation., hypogonadism, and a characteristic
fades (deep-set eyes, mild hypertelorism, overhanging fore­
head, straight nose, and smalt pointed chin), and hoarse
voice (see figure 4.05).''JU" JVI: Associated ocular anomalies
that are apparent in at least SO^-a of cases include posterior
embryotoxon jTtienfeldi anomaly],'-1^' pigmentary retinal
degeneration, pseudopapilledema, chorioretinal folds (see
Rgure band keratopathy, ectopic pupil, eso­
tropia. high myopia, and tortuous retinal blood vessels.
I’Osterior embryotoxon and Lhe peripheral retinal pigmen­
tary changes are the most consistent fitidings and may be
helpful in differentiating this benign form of neonatal jaun­
dice from other more serious causes of neonatal jaundice,
ihe disorder is of variable penet ranсe and is benign in most
patients. Some, however, may have severe cardiovascular
and renal complications as well as progressive neurovascu­
lar deterioration caused by vitamin A and E deficiency.991 '
ihe "'cholestasis'' facies, although occurring frequently in
this disorder, may be seen in patients with congenital intra-
hepalic cholestaLic liver disease unassociated with Alagille's
syndrome.'m The ERG and HOC maybe subnormal.
IN C O N T IN E N T IA P IG M E N T !
A C H R O M IA N S ________________________
Incontinentia pigmenti acbromians ( hypomel,mosis of
Ito) ts characterized by linear and whorled, лтатЬ 1е<аке"
streaks of cutaneous depigmentalion on the trunk and
extremities (along the lines of IllaschkoJ similar to streaks
of hyperpigmenlation seen in patients with incontinen­
tia pigmenti, and anomalies of Lhe central nervous system,
including psychomotor retard aLion and seizures, eyes, hair,
teeth, nails, musculoskeletal system, and. internal organs
>.69 1nсо ntine nlia p igm ent i ach ro mia ns.
A-E: A 7-year-old Latin buy was SE>en because ot progres­
sive caliiract in the left eye, n'.ild visual lots in thie riyht eye,
and lelt excrtropia. H e was Ihe product of a J 7-week gesta-
Li(jn and a breech pelfVeV- Ccnj^j niLal anomalies included
гiц.ЬI ElBmiatiiaphy of the body, incJudin^ lhe tongue ID ) and
palate, crypJorchLsm. and foot deformities; retinal pigment
epithelium ■К РЫj abnormalities we-re nolrcl in the lundi a I
1 month and mynpffl at 1 № уелгь. Abnormal dentilU n It:,
alopecia are,Ha, ощГпевэ, and streaks pf cutaneous hypopij;-
mentataon ihypomjj l a n ™ s of Но] i.C" occurred before 5 years
o! afj,e. Visual acuity in the ri^hl eye ( — Й.00 was 20/50
and in lhe lefl eye f — 4.50 D j was hand т с п е ш Й Й . There
were bilateral cortical cataracts, worse ir Lhe left eye. The
rif^ht fundus showed лп anomalous optic disc, coiifse st-nealtK
and changes in the (A and Bi. tlectrorelino^rapbic find­
ings showed reduced rod and t o tie amplitudes.
Hypo melanosis of Ito associated with
m ed till oblasto ma.
F-L: This 14-year-old Eemale was operated for a medullo-
blastnnla and was found (o have a con^enilal № k le defor­
mity and whorfs ol skin pigjnen I al ion along the lines
ot' Blanch ко. A trisomy ot" chromosome 3 Was found on
genetic testing, a defect so far not known (o be associ­
ated with medullobiaslon'.a. bhc? had pundate areas of K P t
hypopi^rrentafion more visible in the rr^bt than Lhe left
macula iF i*nd C ), that were hypoautofluorescenl (H bind I
and appeared as transmission defects on angiography -!J
Her visual acuity was normal in both eyes, lh e streaks of
hypcipigmentation were present on her back IK:. forearm (L:.
and race. There was по Га mi Iv history of medical disordert.
[E'igure ifiS )? ™ - ™ ' 'lhe name "incontinentia pigmenti
acrottklaiHi:* should not link this condition with incontinen­
tia pigmenti, which occurs only in females (transmitted by
X-linked inheritance and lethal in males); (hey are in no
way related, except for the superficial resemblance of the
skin changes. Incontinentia pigmenti achromians occurs in
both sexes with a female-to-male raLio of 2.5:1 and geneti­
cally is not well defined.'" : Evidence documenting
single-gene transmission is unconvincing and recurrence
risks in the same family are negligible in most cases.
Karyotyping of blood lymphocytes, skin fibroblasts, and,'or
keraiinocytes of li5 individuals reported in the literature as
reviewed Ijy Sybert11)1" revealed abnormal chromosome con­
stitutions in 60. ЧЪгее patients were 46,XX/46,XY chimeras,
and two were 46,XX,'46,XX chimeras. .Vlost patienls were
mosaic for aneuploidy or unbalanced translocations, with
Lwo or more chromosomally disLinct cell lines either within
the same tissue or between tissues. Hie common alterations
were mosaic trisomy IS, diploidyi'iriploidy, mosaicism for
sex chromosome aneuploidv. microdeletion of the proxi­
mal legion of Щ and lelmsomy
beaLures frequently seen in incontinentia pigmenti such as
vesicobulfous and verrucous phases predating the skin pig­
ment changes and severe relinal vascular anomalies leading
to blindness (see bigure 6.6У) are not seen.
 A Variety of ocular а й р [Ш ю including strabismus, epi- 5.70 Heimler syndrome.
canthal folds. со Ioho ma, myopia. microphthalmos. corneal
A—H: Th is- 1 b-vtfar-oId S e ir a n was dtscriliud by L>r. Hoi in lor
asymme^y, atrophic irides., irregular pupilr heterochro­ in 1У91 w hen sHii was (j years of aj^e w ilh denial and riaf)
mia of the iris, cataract and retinal detachment, have been anomalies C and HV. Лп <н:и1аг eHamirfltioli was тш1 per­
reported.|0Й|,11)|'' Streaks of hypopigmentalion of the formed nit I ha I time. BoLh eyes- now had jjiayinj* ol Lht1 роъ-
ii]°L and optic disc anomalies occurred in a 7-year-otd boу terior pole at [lie Itfirel of [he rc.4irtbiI pi^imenl epilholium,
with incontinentia pigmenti achnomiansseen at (he Bascom yxtondirrf; up to the ecAiator -A and ttj. Visual Jt u ily was
20/40 in each eye. O ptical coherenLe Lontography showed
Palmer Jiye Institute [figure 5.69A-E).™5 I ie also had bilat­
tyhls/schisis cavity in the гласи la fE ап-d hi. Autofluortyseence
eral congenital cataracts* myopia, and dental anomalies.
imaging revoalud punctale hvper- and hypoautoliuofes-
Other cases with ocuEar changes limited to pigmentation cen! changes in both eyes Iha I w ere symmetrical (C und D:.
of the fundus alone without visuaE compromise have heen Electrorminrj^ram showed mildly subnormal amplitudes for
described.10] 1 We have seen an 18-year-old female with tones and w ilh in the normal Ш е for rods.
meduLloblastoma, dim orphic facies including epicanthic fA —H , O lU M l'S V III JJr. lrLJllL' .-lILl D r . I ,-:WrrJn.:.LJ ’гиппи^ л!
folds, broad nasat bridge, congenital ankle deformity, and
bilater.il large great and second toes wilh extensive whorls
of skin pigmentation following lhe lines of ttlaschko, espe­
cially on the face, bacl<r and arms {I'tgure 5.69F-L}. She
(white dotsj on their finger- and toenails With hypoplastic
was visually asymptomatic and her fundus showed patchy
enamel in their permanent teeth - more so the molars, wilh
depigmentation of the RPE {figure 5.6&f:-|}. She was found
relative sparing of the incisors [figure 5.70G and 11J .' :1*
to carry a partial duplication of the long arm of chromo­
lhe primary dentition is normal in all cases, '['he condition
some 3 (46rXX, dup (3) {q23q27}.
is believed lo be autosomal-recessive; subsequendy there
Overall, it appears that the skin changes of hypomela-
have been three reports in two siblings one sporadic case,
nosis of [to are associated with a variety of chromosomal
and a set of mouo^ygolic twins.llllS Ehe original patient
anomalies rather than a specific gene defect; hence it may
described by HeimEer was recently eitaniined at age 26 and
bes! be addressed as a feature rather than a disorder as
found to have visual acuity of 20/40 in each eye. symmet­
suggested by Sybert.
ric widespread gray white changes at the pigment epithelial
level throughout the posterior pole, and cystoid macular
H E IM L E R S S Y N D R O M E ______________ edema in both eyes [figure 5.70Af Б, \Lt and t-'). lhe pig­
ment epithelial changes correspond to punctate decreased
1 leimler el
aE. in 1У91 described two siblings with sensori­
and increased aulofluorescence [Figure 5.70C and [}). FUG
neural deafness that began in early childhood, associ­
showed mild decrease in scotopic and pholopic function.
ated with beau's lines [horizontal ridges) and leukonychia
C O C K A Y N E 'S S Y N D R O M E
Lockiyne's syndrome is an jj|tofio teal -recessive form
of dwarfism associated with premature aging. character­
istic vbind! ike" facies, microcephaly, sunken eyes, beak
nose, prognathism. disproportionately Eaige hands and
feet, flexion contractures of the limbs..- kyphosis, hearing
Loss, intention tremor, nystagmus., ataxia, muscle rigidity,
incontinence, mental retardation, hypeipigmentation and
photosensitivity of die skill, 1'salt-and-pepper'T retinopa­
thy with waxy optic atrophy, and narrowed retinal ves­
sels. _Ui l: "]Q|:> Vis Ion is generally poor. K.lectrorelin{)graphic
findings arc normal or minimally abnormal. A French
family of four brothers whose parents Were first cousins
showed hypermetropra and bilateral maculopathies with
decreased cone amplitudes in all four. No retinal vascular
or pigmentary changes were seen. Ilteir mother had uni-
EateraL peri pap iПату pigmentary retinopathy on the left
side and the father was normal/" 4'
On the basis of a neuropat ho logic finding it has been
regarded as a leukodystrophy and a subgroup of the
Ffciizaeus-Mer/bacher disease. The basic defect is unknown.
1LisLopathology show evidence of loss of nerve fiber and
ganglion cells as xvell as loss of photoreceptor cells, irregu­
lar hypopigmenlation, hyperpigmentation, and migration
of pigment cells into the retina and subretinal space.101"
H ER ED IT A R Y M IC R O C E P H A L Y A N D
RET IN A L D E G E N E R A T IO N ____________
Although the association of chorioretinal degeneration,
electroretinographic abnormalities, and microcephaly
has been reported most often in families with autosomal-
recessive inheritance, it may occur in families with autoso­
mal -dom inant inheri tance.10J1
O S T E O P E T R O S IS A N D
C H O R IO R E T IN A L D E G E N E R A T IO N
Osteopetrosis is a group of hereditary metabolic diseases
characterized by increased bone mass caused by defec­
tive bone resorption. It is subdivided into juvenile- and
adult^nsft types. Infantile malignant osteopetrosis is an
autosomal-recessive disorder present at birth and is lethal
during childhood unless treated. Osteoclast dysfunc­
tion causes abnormal bone resorption, thickened corti­
cal bone skeletal defects, and frequent bone fractures.
I Lemato logical abnormalities due to bone expansion into
Lbe marrow space with extramedul’ary henialopoiesis are
present. Hearing and visual loss may occur as the result
of encroachment on the auditory and tip Li с foramen,
optic atrophy, or progressive retinal degeneration. ' as parafoveal sub retinal pigmenL proliferation. Classical
KetinaL degeneralLon may be evident on ophthalmoscopic
examination as depigmentation and aLrophy of the pig­
ment epithelium in the macula,111' ■ ' or electroretiпо-
graphical ly in patients whose fundi are within normal
E L m it s . sCQ-i thorough neuroradLologLc and imaging
studies and electroretinography are important in these
children when they present wLlh poor visual function.
optLcdisc pallor, and oLherwLse normal fundi before pro­
ceeding with suigery to decompress the optic foramen.
The optic foramen may show only minima! narrowing,
and most of the visual Loss may be on the basis of the pro­
gressive retinal degeneTattoil^ 1
Allogenic hematopoietic stem celt transplantation done
early in Lhe course has resulted in survival and Increased
life expectancy in these ch ild ren ."4, Mutations in the
Tcirgl (Atp6V0a3), locus which encodes the a3 subunit of
the vaculolar-type proton-transporting AL'Pase, an enzyme
involved in the development o f visual function, es known
to cause half Lhe cases o f severe autosomal -recessive
osLeopeLrosis.1^ 1™
P E R IO X IS O M A L D IS E A S E S ___________
Malfunction of die peroxisome, a subcellular organelle,
results In several childhood ophthalmological disorders.
'L'hese disorders have been divided Into three groups: f l)
defective biogenesis of Lhe peroxisome (Zellweger syn-
dromer neonatal ad renoleukodystrophy, and infantile
Ke [sum's disease); ( 2) multiple enzyme deficiencies ( rhi­
zome! Lc chondrodysplasia punclata); and (3) a single­
enzyme deficiency (X-l Inked adrenoleukiodystrophy,
primary hyperoxaluria type T).
Zellweger syndrome, the most lethal of the three per­
oxisomal biogenesis disorders, causes infantile hypoto­
nia, seizures, and death within the first year. Ophthalmic
manifestations Include comeal opacification, cataract,
glaucoma, pigmentary retinopathy, and optic atrophy.
Neonatal adrenoleukodystrophy and infantile Refsum's
disease appear to be genetically dlstlncL, but clinically,
biochemically, and pathologically similar to Zellweger
syndrome, although milder. Rhizcimeiic chondrodyspla­
sia punctata, a peroxisomal disorder which results from
at least two peroxisomal enzyme deficiencies, presents
at birth with skeletal abnormalities and patients rarely
survive past 1 year of age. lh e most prominent ocular
manifestation consists of bilateral cataracts. X-linked
(childhood) adrenoleukodystrophy results from a defi­
ciency1 of a single peroxisomal enzyme, and presents in
the latter part of the first decade with behavioral, cogni­
tive, and visual deterioration. Lhe vision loss results from
demyelination of the enlire visual pathway, but the outer
retina is spared. Primary hyperoxaluria type t manifests
Kefsum's disease is also a peroxisomal disorder.
Cerebrohepatorenal Syndrome
[Zellwegers Syndrome)
Zellweger's syndrome is a inliLliiyitem Congenital disorder
characterized by severe central nervous Ftyb-t^jn. Involve­
ment (hypotonia, seizures, and psychomotor retardation),
hepatic Interstitial fibrosis (jaundice, hepatomegaly, hypo-
prothrombinemia, and gastrointestinal bleeding), mul­
tiple renal cortical cysts, calcified stippling of the bony
epiphysis, characteristic facies (high forehead, microgna­
thia, flat supraorbital ridges, and high arched palate), and
in some patients evidence of a tapetoretinal degenera­
tion. 1029Most of these patients die within the first year
of life. 1 listopatbologic examination reveals changes simi­
lar lo retinitis pigmentosa.1:Jh Ultrastructural examination
shows bI leaflet inclusions of the KPh. These patients have
an excessive amount of veiy-long-chain fatty acids in the
ocular tissue. These histopathologic and biochemical find­
ings are simitar lo those in neonatal adrenoleukodystro­
phy a metabolic neurodegenemlive disorder characterized
by generalized visceral dysfuncLlon. central nervous system
white-matter degeneration, and adrenal hypofunclion.i:",L
A D R E N O L E U K O D Y S T R O P H IE S
I he adrenoleukodystrophies are a group of rare disorders
that include a childhood-onsel X-Einked variant [Schilder's
disease), adrenoleukomyelo nephropathy, and neonalal
adrenoleukodysirophy. Patients with all three disorders
demonstrate central nervous system demyellnlzatlon,
ail renal cortical atrophy and/or lamellar inclusions,
and increased serum levels of long-chain fatty acids.1031
features of neonatal adrenoleukodysirophy include:
onset of hypotonia and seizures in the neonatal period,
visual loss, optic atrophy, calaracl, pigmentary retinopathy
(50^'a), autosomal-recessive mode of inheritance, long-
chain fatty acid in multiple organs, and diminution In size
and number of hepaLocellular peroxisomes.Ш| The mean
age of death is Ъ years. Histopathologic and ultras Lruc-
tural changes in the eye include loss of the ganglion cel!
and nerve fiber layers, oplic atrophy, atrophy of the retinal
receptors, cystoid macular edema., pigment cell migration
Into the retina, cataracts, and characteristic blleafiet inclu­
sions in retinal macrophages, pigment epithelial cells,
photoreceptor cells, and vitreous macrophages.!03Q,]LlJI
Zellweger's syndrome is similar lo neonatal ad reno­
leu kodystrophy but is associated with renal cysts but no
adrenal cortical atrophy (see Zellweger's syndrome). The
features of childhood adrenoleukodysirophy include:
onset al 4-S years of life of progressive dementia, gait
disturbances, visual loss, primary adrenal insufficiency
leading to skin pigmentation and symptoms of hypo-
adrennilism, X-l inked recessive mode of inheritance, mor­
phologically normal hepatic peroxisomes, and death In
adolescence.| :' ' Visual loss is primarily caused by central
nervous system demy el inidation, bul ganglion cell degen­
eration may also be operative, legmenlary macular changes
occur in some patienls.Adrenoleukom yeloneuropathy
Is associnited wilh lale-onset [range 20-30 years) hypogo­
nadism. spaslictjLiadriparesis. and X-l inked inheritance.
R E F S U M 'S SY N D R O M E:
(H E R E D O P A T H IA A T A C T IC A
P O L Y N E U R S T IF O R M IS )
Kefsum's syndrome is a familial disease characterized by
night blindness, atypical pigmentary retinal dystrophy,
chronic polyneuropathy, cerebellar alaxia, and elevated
cerebrospinal fluid protein without pleocytosis.
]TiIs. disease begins insidiously in either infancy or early
childhood. Ihe average delay in diagnosis of Etefsum's
disease is approximately Ю years after the diagnosis of
retinitis pigmentosa.*0^ Cataracts, ichthyosis, skeletal
anomalies, and electrocardiographic evidence of conduc­
tion defects frequently appear, bomt patients develop
hearing loss, lhe pupils may be small and nonreactive.
Oculomotor apraxia may be seen, 'lhe LiRC amplitudes
decrease as the disease progresses. EJeath is caused by heart
failure or respiratory paralysis.
'IllIs is a recessively inherited disorder of lipid metab­
olism with mutations in the gene encoding a peroxi­
somal enzyme phyla noyl-coenzy me A alp ha-hydroxylase.,
which results in the inability lo alpha-oxidize phytanic
acid.IU' 7 , As a result phytanic acid, which is not an
endogenous product but Is supplied with food mainly as
phytanic acid or its precursor, phytol, accumulates In the
urine, plasma (normal, с 1 |imol/l),and body tissues and
nerves Two hypotheses have been postulated: ( I ) phy­
tanic acid methyl groups may act to destabilise the myelin
Eipid layer in axons; or (2) the phytanic acid may replace
Long-chain fatty acids in phospholipids and triglycerides*
resulting in decreased function of the affected tissues. In
the eye, abundant fat-staining substances have been Found
within the RPii.: this may eventually lead lo photoreceptor
cell death. Eislerilocation of vitamin A with phytanic acid
may also lead to the demise of photoreceptors, treat men l
wilh a diet low in phytol and phytanic acid reduces
plasma phytanic acid levels and causes some improvement
in neurologic signs!l" ' and may retard the progression
of relinal degeneration.1 Plasmapheresis can help
lower Serum phytanic acid Eevels in severe metabolic aber-
Ш^опя^ " -14 ’ ' Early diagnosis, however, Is important Lo
prevent development of the neurologic complications.10''
C EREBRO -O C U LO H EPA TO REN A L
S Y N D R O M E (A R IM A 'S S Y N D R O M E )
Arlma's syndrome consists of characteristic facies (bleptta-
roptosls and telecanthus], nystagmus, Ijeber's amaurosis.,
hypo Lon la, profound psychomo tor retardation, agenesis of
cerebellar vermis, infantile polycystic kidneys, progressive
chronic renal insufficiency, and Elver disease.]Cl4b Its fea­
tures are similar lo those of ]outurf's syndrome, which in
addition includes infantile episodic respiratory abnormali­
zes Lbat may be life-threatening.1'■
;^|СчТ
j.7 E Spinocerebellar atrophy (5CA7}.
A—G: Ttiis 36-year-old m ale complained o f decreased vi-sion
in Licilh eves; fa* 10 yeafs. He* had а 5-укзпг history ol" f^ail,
Eimb, and speech ataxia. His vision was 2СУ1 00 in each eye
wiLh bi Lateral ( ц-пIriLt scutomija tt.. Bolh foveas wure Ibinned
out with reddish coloration |A-E3j. A foveolar w ind ow dfifot I
was seen on ii fluorescein il? and Ei and no changes ал an
in d p c y ^ ilie green angiogram 1F.l. E led noneti no^ram showed
diminished rod and co n e function. Foveal phoEoceceptore
were lost on optical coherence tomography (0|T- His gene
Leiting showed 4fl f.'ACi repeats on Lhe A T X N 7 gene consis­
tent with SCA7.
C H O R IO R E T IN O P A T H Y A N D
P IT U IT A R Y D Y S F U N C T IO N __________
Lhe syndrome of chorioretinopathy and pUnitary dysfunc­
tion is characterized by severe congeniLal or early-onsel
atypical pigmentary retinal dystrophy; hypothatamic-pilu-
itaiy dysfunction manifested by growth retardation: sexual
infantilism; hair abnormalities, including long lashes,
sparse, fine scalp hair, long bushy eyebrows (Lrichomeg-
aly}, and failure to develop post pubertal hair patterns;
and perhaps, Lo a lesser degree, hypothyroidism. u^e-uisi
Jxss consistent features include low birth weight, abnor­
mal pregnancy, and mental retardation. Patients may show
an extinguished ERG, widespread areas of thinning and
coarse clumping of the RE^i.
R E T IN IT IS P IG M E N T O S A
A N D A U T O IM M U N E
P O L Y E N D O C R IN O P A T H Y____________
During childhood or early adulthood, patients with Lype
] autosomal-recessive autoimmune polyendocrlnopathy
develop hypoparathyroidism, mucocutaneous moniliasis.
Addison's disease, and keratoconjunctivitis.1,1 This
syndrome may also include chronic hepatitis, malabsorp­
tion, pernicious anemia, alopecia, and primary hypo­
gonadism. A few patients may develop typical retinitis
pigmentosa."1''' E have seen one such patient and the medi­
cal records of another. Neither had evidence of malabsorp­
tion, and both had normal serum vitamin A levels. Ihe
occasional association of retinitis pigmentosa with type i
pDlyendocrinopathy may be related to the proximity of the
gene locus for these two disorders, which in the case of the
polyendocritiopalby, has been assigned lo chromosome
Wood and coworkera observed the development of
an asymmetric fundus picture of retinitis pigmentosa iti
a young man with lype L autoimmune polyendocrinopa-
thy."' ' E'hey demonstrated markedly elevated titers against
(he retina and optic nerve and hypothesized that Lhe eye
findings were autoimmune and part of the syndrome.
 ftcfj'ptifif Pifim ciitosf. ami Aithiitnm uhe Potycndxrinapathy 399

®
A T Y P IC A L T A P E T O R E T IN A L
D Y S T R O P H Y A S S O C IA T E D W IT H
O L IV O P O N T O C E R E B E L L A R
A T R O P H Y K O N IG S M A R K T Y P E III,
H A R D IN G TYPE II
^typical tapetoretinal dystrophy associated with сегеЬеЩг
ataxia is an autosomal-dominantly inherited disease char­
acterized by loss of centra] vision that is caused by atrophic
changes of the retina and RPii. which are initially confined
to the macula but which gradually spread to involve the
peripheral fundus (Fteure 5.56Г—I) .: Patients with
infantile-onset disease typically have pigmentary changes
and exhibit a rapidly progressive course that often leads
to early death.lUc,|: Later onset in childhood is less severe,
and aduh-onset disease is accompanied by relatively mild
and slowly progressive cerebellar degeneration and cir­
cumscribed macular lesions.т й borne patienls may have
pyramidalr extrapyramidal, and brainstem dysfunction,
findings in some patients may include dystonia., nystag­
mus, internuclear ophthalmoplegia, progressive ophthal­
moplegia, ptosis, and disturbances in esophageal, bladder
and bowel funcLion. iilectrophysiologic testing may be
normal early but severely abnormal in the later stages of
Lbe disease, Some patients have progressive external oph-
Lbal moplegia. 1listopathologic and ultrastructural findings
in the infantile type ]]] olivopontocerebellar atrophy and
degeneratioii show retinal degeneration affecting primarily
the retinal receptor layer with maximal involvement being
in the macular area, striking variability in pigmentation
of the RPiv osmiophilic multi me mb ran оus and complex
lipo fuse in inclusions in conjunctiva, keratocytes, lens epi­
thelium, iris and ciliary body iibrocytes, outer retinal ceils,
and pigment epithelial i5lc]u.
sions are similar to those seen in the neuronal ceroid lipo­
fuscinoses (NCL). Unlike in the latter patients, however
there are no curvilinear inclusions.
Olivopontocerebellar degene rati oil type Ш should be
suspected in infants presenting with a neurodegeneralive
and retinal degenerative picture, these patients should
be differentiated from those with the infantile form of
NG[„ in fail tile phytanic acid storage disease, abetalipopro-
teinemia, and recessive neonatal adrenoleukodystrophy.
Detection of evidence of the disease in a parent and clini­
cal evidence of ataxia are important findings to differen­
tiate this from the other disorders. Conjunctival biopsy is
helpful to confirm the diagnosis but does not differentiate
it from the lipofuscinoses, t-'amily members with normal
fundi and visual acuity may show ERG changes.Ш7
j.7 i Continued
H - M : This; 2В-уе^г-оЫ African Am erican worn^n bad я
family historv of decreased vision in m<jLhor, л sis1er. and
a brolher. Heir FAQfher ta.fried a diagnosis of m ultiple scle­
rosis. O n e other sister had normal vision. She was a type 2
diabetic for 5 years, She u jm p la in rd of dccreased vision in
berth eyes and said her vision was better at mghL. 5ihe was
a —В .50 myope with sigmficarcL a&tigrrcatisrn ol +3.25 on
Lhe ri^hl and +■!>.25 on lh e left. Vision was- 10/200 in each
eye. H e r fundus was rwrirul -:H and 1l artd HVF showed cen ­
tral scotoma in boLh eyes. N b specifee: diagnosis could be
made and whtin ie-o\amined 2 vears laLer her fundus was
si 111 li nrem ciikable With 2 0/4 CO vjsion rn both eves. Three
years. laler the mp^ufa developed bull's-eye-[ype change in
oath foveijfs, more prominent on lhe rigbl ihi^n Lhe left | .
which conlinLied lo i&olyfe over Сhe пел I 2 years. The Luteal
change was hypoautofliffWesLenl iК '■and showed a w in d o w
defect an angiography (LI. O p tical coherence [oncography
Lhiou^h [he fovea confirmed loss of Lovell cones and ihin-
niny of inner retina !M^. O ve r lhe В years she w js followed
her ataxia processed and she becam e wheelchair-bound.
She and her mother tested positive fof CA£j repeats on 3p12-
1J , confirming lhe dingn<jsrs o f SCAT.
l A —i_ i . -LOLirlL^-v' U r . Io il ; PuIjiJo. H d u U H c i y o f L Jr. ItM1! VulCer.l
Spinocerebellar Ataxia 7
SC]A 7 is an autosomal-dominant neourodegenerative dis­
ease with progressive reUnal and cerebellar degeneration.
ClEnical features in patients with SC!A 7 consist of early
blue-yellow color blindness, progressive visual iinpair-
ment with central vision becoming compromised first.
The fundus m;ry look normal in the ear!y stages of the
disease, then dew lops a subtle reddish change with thin­
ning (figure 5.71Л and b) that can be discerned only on
high-resolution OCT! Imaging. Progressive RPL hypopig-
menLation ensues that manifests as window defects on
angiography (figure 5.71 ID), lbe О СГ at this stage shows
complete loss of fovea I photoreceptors (]:igure 5.71 G).
Ibese changes are usually accompanied by progressive
limb ataxia. dysarthria, slowing of saccades, and ophthal­
moplegia. Patients become wh eel chair-bound over time.
Gene ataxin is expressed in the brain and eye. 'lbe repeat
expression of СAC gene causes cytotoxic gain of func­
tion of the protein and aggregation, resulting in structural
changes to the involved tissue. lhe repeats are unstable
between generations, and this results in anticipation in
the children of these patients, lhe higher the number of
repeals, the more severe the disease manifestation.
PA N T O T H EN A T E
K IN A S E - A S S O C IA T E D
N E U R O D E G E N E R A T IO N
(H A L L E R V O R D E N - S P A T Z
SYN D RO M E)
Pantolhenale kinase-associated neurodegene ration,
formely к now [i as Hallervorden-Spatz syndrome. is char­
acterised by the early onset of an exlrapyrami dal motor
disorder (dystonic posturing, muscular rigidity, choreo-
aLheloid movements, ataxia, hyperreflexia. and spasticity),
dementia, iron accumulation in the brain, and a relenl-
tes-sly progressive course leading lo death in early adult­
hood. ' 10 ' Approximately one-fourth of these patients
w ill demonstrate retinal degeneration that initially may
show only mottling of the RPH bul subsequently may
show evidence of a flecked retina and later bone spicule
formation and a bull's-eye annular maculopalhy." " L'here
Is some evidence lo suggest that those patients wilh the
retinal findings have an earlier onset of lhe disease and
a much more rapid course, with death occurring In tale
childhood. Some patients have an associated acanlho-
cytosis and normal beta-lipoprotein level s . ' Pupillary
ah norm aLilies resmbling Adie's pupil, poor convergence
reflex, patchy loss of pupillary ruff, and sector iris atrophy
are seen in some patients, likely due to proximal degen­
eration of the fibers deslined to the iris due lo iron depo­
sition in the mid brain in or near lhe substantia nigra."'"'
Palienls wiLh a variant of I lallervorden-Spalz syndrome
have hypoprebelalipoproteinemia, acanthocvtosis, reti­
nitis pigmentosa, and pallidal degeneration (H ARP syn­
drome).10'" Computed tomography of the brain may show
basal ganglia opacities and 'П-weighted .VIЩ shows char­
acteristic abnormalities of the globus pallidus described as
"eye of the tiger17sign (much darker with a central bright
spol).l0r' ■n' ■°1’' Neuro pathologic criteria for diagno­
sis include: ( ]) symmetric, partially destructive Lesions of
Lhe globus pallidus; (2) widely disseminated rounded or
oval non nucleated structures ( "sphenoids'7J, identi hable
as swrollen axons, especially numerous in the globus pal-
[idus and pare reticulata; .ind (3) accumu3alion of pig­
ment, much of it containing iron, in lhe affected regions.
3listopathologic examination of the eye shows absence
of lhe pholoreceplor cells, attenuation of lhe plexiform
and outer nuclear layers, normal inner retinal layers and
degenerative changes with accumulation of melanofuscin
b.72 Kearns-Sayre syndrome,
A -С: This- 16-уелг-old 1Чтлл1с! w ilh atypical p if^ e riflB y reLi-
nal dystrophy, exlernai ophthalmoplegia (A). t.t)nnple4e heart
Ыог:к, arrt&rtdrrhea, and nularded growth had S^jkra-AjfldtorW
attacks Lhal w ere relieved by a cardiac pacemaker. Her
visual acuity was 2QV25. There was concentric: contraction of
lhe visual fields tu colur lest objects. DiiTuse pigrnenl abnor­
malities thiil wtf-пи not brurninenl t^jhrhalm0£copically were
r e a № apparcml angiographic ally.
D - H : This ЗЧчУч^Г-dld black man with heart blof:k com ­
plained of ptosis of both eyelids of several years' duration
(Dj. Nole lhe plaque of hyperplastic retinal pigment epilhe-
liLim :К HE nasally (EJ and m auling o f the RI?E: in ihs тасиЗл
i Г . An^io^nphv- uhtjavs coarse patfeln of hyperfI исхетсепсе
fti and H|.
in the [her€ вдц accumulations of Rl]li
cells as well as extracellular pigment around equatorial
blood vessels.lD7^l0ftl Jbe disease is inherited aulosomal-
recessively secondary lo mutations in the gene encoding
panlot hen ale kinase 2 (PANK2J located on chromosome
20pl3, involved in the biosynthesis of coenzyme A.
103 Deficiency of PANK2 enzyme results in accumulation
of cysteine in the globus pallidus. causing neuronal death.
'Ibe exact mechanism leading lo iron accumulation In the
area is not understood.iaee 'IWo forms, classic or early-
onset, with a more severe phenotype and progression, and
an atypical form, adult-on set slowly progressive parkin­
sonism, are known. M-::-
M IT O C H O N D R IA L
EN C E PH A L O M Y O PATH IES___________
4'he mitochondrial encephalomyopathies are a group of
clinically heterogeneous disorders that share common
biochemical and morphologic abnormalities in the mito­
chondria. Ibis group includes the Kearns-Say re syndrome.
MTEAS syndrome,: and MtRfcF syndrome,1
A patient who shows features of two or three of these dis­
orders is referred lo by some as having a mitochondrial
euceph alo myopathy overlap syndrome.-'"1' A number of
DMA mutations have been localized in patients wilh these
disorders. L|L"- Interestingly, in. some instances a specific
gene mutation can account for more than one phenotype.
TWO patients wilh the overlap syndrome demonstrated
identical mitochondrial Df\A mutations al nucleotide
position 3243 (\li£J AS mutation}. |0'J 7
Kearns-Sayre Syndrome Ъ.72 Continued

Kearns-Sayre syndrome is л гаге sporadic multisystem l- L: This 14-year-old boy w ith Keams-5ayre syndrome?
develofied pttftis and feKtricled eye ГСю^ЕГпепЬ л1 9 year*
mitochondrial disorder niffectiiig the centra! nervous sys­
йГ Age. He knd mild neduclion in visual acu ily and sub­
tem, muscles, and endocrine organs. Clinical features normal e le c trd ^ Iira g ^ p tlic findings. There were mcrilled
Include atypical pigmentary retinal dystrophy (kigure pigmentary changes in ib y mafiul^f л rtiFi (I rind I lhal were
3.72), myopaLhic external ophthalmoplegia with the onset relatively inappafenl in litis blond fundun. He dcvelopud
of ptosis in early childhood,. ,ind heart block .1:01 Other купе орлГ attatfcy ал-ri heart block 5 monlhs betore dealli fol­
features that may be present include widespread muscu­ lowing CDftfclicatiorti of лп upper nespintlory mfectiorv His
lar dystrophy, deafness, vestibular dysfunction, elevated eyes were obtained al диЮрыу. HistopalEralogic examination
re vK i’ed evidence nfrptjfpigjnen tatlon and dupigmenlatitju
spinal fluid protein, dwarfism, hypogonadism, cerebel-
of lhe K^L IK). In ь о т е нгалн there Wiia evidence ol stime
Ear and corticospinal dysfunction, endocrine dysfunction, lass of Ibe retinal receptor elements. Tbe retina and choroid
nephropathy, and comeal opacity.IL|1' ■Jt " uRagged-redv were athefWjJaP Unremarkable. Then’ were- marked скйейега-
myopathy anti spongiform degeneration of lhe central tive changes involving lhe extraocular muscles HL l. Sim ilar
nervous system are characteristic histopathologic find­ alleratrons were noted in (he muscles ol" Lhe Tower Ktlremi-
in g ."04 Ihese patients usually have excellent visual func­ Lies.. shoulder girdV1. and diaphragm.
tion. '['here may be some loss of central vision in later life,
l.ess than 50% experience nyctalopia. Diplopia is uncom­
mon. ']he characteristic fundus finding is the presence of
widespread salt-and-pepper К ETti mottling that Is most yet nonspecific (figure p7 2LJ.ll0li--Ljll-llLJ Liter there may
striking in the macula and deplgmentation of the RE*k in be Eoss of the R P t and receptor cells that is most marked
the peripapisEary area (Figure 5.7211, E, ¥t lr and |). '['here in the macular area (E'igure 5.72K). Ultrastructural study
is rarely evidence of pigment migration into the overly­ reveals enlarged mitochondria in the basaE part of the
ing retina. lhe retinal vessels are of normal caliber, and RE3E:, the photorecepLor ellipsoid, outer plexiform layer,
the optic disc is normal. 1л ter in life some patients may and nonpigmented cisiary epithelium.111-),] 11,1 Macrophages
develop a picture more closely simulating retinitis pig­ containing phagocytosed lamellar discs were present in
mentosa and in a few cases demonstrate severe chorioreti­ the subretina] space. lhe clinical and histopathologic find­
nal atrophy simulating choroideremia.111'7' lhe LOG may ings suggest that the primary disease affects the Kl3k and
he normal or subnormal. The LRO may be subnormal or that the posterior fundus is affected more than the periph­
extinguished. A patient wilh findings typical of adult vi tel - eral fundus. L'he use of systemic corticosteroids In these
liform pattern dystrophy has been described recently - a patients may precipitate hyperglycemic acidotic coma
feature similar to that seen in patients With MkMS/MEDD, and death.L]0j A simitar syndrome but wilh progressive
signifying changes affecting the ItP E .l]Lfl l-.arly in life the optic atrophy and absence of tapetoretinal dystrophy may
histopathologic changes in the eye may be confined to an occur,” ' 1,
irregular area of hypopigmentation and hyperpigmenta­
tion of the tj:PEr macrophages in the sub retinal space, mild
loss of rod and cone cells (llgure 5.72KJ, and dystrophic
M ID D/ME LAS
changes in the extraocular muscles that are characteristic See earlier section under pattern dystrophies.
D A N O N D IS E A S E
Danon disease Is а rare X-3Inked di sorder characterized by
cardiomyopathy, skeletal myopathy and mental i£fairia-
1:10-1"- The; skeleLal myopathy is generally mild
and the menial retardation variable and Oonprogressfi^
but cardiomyopathy is progressive and determines the
outcome. Mutations in the LAMP2 gene on Xq24 have
been shown to be responsible for the disease, the cellular
pathogenesis being caused by a deficiency of lysosome-
associated membrane protein-2 I Ь\М Р 2). lysosomal stcjr-
age occurs in this disorder, with elevated muscle glycogen
in spite of normal t\-g[ucosidase activity. C]ylopl,ismic
vacuoles containing autophagic material and glycogen
are seen in skeletal and cardiac muscle cells. An animal
model, the lamp2-deficienl mouse, shows reduced weight
and increased mortality, with accumulation of autopha­
gic vacuoles in many tissues, including skeletal and heart
muscle, liver, pancreas, spleen- and kidney, in hepalo-
cytes, the autophagic degradation of long-lived proteins
is severely impaired, cardiac myocytes are ultrastnictuially
abnormal, and heart contractility is severely reduced.'''"
Jbe affected males present early in age {2-3 years) with
fatigue and show evidence of progressive hypertrophic car­
diomyopathy end secondary arrhythmias, the commonest
being W olff-Parkinson-White. Unless a cardiac transplant
is done, death can occur suddenly from an arrhythmia or
due lo progressive heart failure from a heavy heart and
thickened venlrlculnir wall and interventricular seplum.
Women present later in life, in the fourth decade or later
(I'igure 3.73H -JL with signs of dilated cardiomyopa-
Lhy.Kl " lhe less severe disease in women is likely from
irregular lyonizatlon of the X chromosome.
Male patients have moderate decrease in vision in lhe
20/40-20/60 range and may complain of nyctalopia
while women may have normal or near-normal acuity,
ibe retina of affected men shows diffuse loss of RjPE and
choroidal pigment resembling the fundi of choroideremia
(I'igure 5.73A-C, li and С ), though may not be as severe.
Women show annular mid peripheral and peripheral fine
pigment mottling [Hgure 5.73H-I) resembling sall-and-
pepper fundus of rubella and the carrier stale of choroi-
deremia. Huorescein angiogram delineates the pigment
moLtling better [E'igurv 5.731> and li). Eilecloreli nogram
in affected males is subnormal and mildly affected in
women. i.ens changes in Lhe form of stellate dots or fine
flecks may be present.1'1'"1 w"r>" u' Macular changes have
been mentioned in one case but no images are available,
lyin g (he ocular findings with lhe cardiac history is impor­
tant to make the diagnosis, which in turn can save the
patient's life with a timely heart transplan!.
j.73 Darmn disease.
A—G: This 35-year-old visually asym plom alic male was
found lo haviu 20/20 vision with livpupiymcnlt'd pate Itus
□E lhe relinal pigment epithelium in both eyes (А-Ск
Anj’ ioj’Trim reveafed punclale 1оск<хЗ fLo ru ^ ^ n o t! drum pig­
ment iD and fc'. Three years lator the fundus ярреапэгн:е was
Unchanged jn bolh eyes iF and (j). H is otJtilaT p ca m ii^ lib fl
wan prompted by hiн mt’dical findings o f pS£diomyopa(h$
requiring hesft lranaplflnl.
H - J: Visually asymptomatic sFsler ol a patient with cardja-
myopalhv and anhylhm ia ^howud fine moLtling of piemen I
more prominent outside the posterior pole. Eleclroretinogram
amplitudes w ere normal but impEfcil limes wore prolun^ed.
lA - C j , t (> u rlL " :y ОЙ I J r . М л Ь п г л \ , --г.|; H - J r t o u r k ' s y erf I J r V ir e s h
Mahtddvj.l
B A S S E N - K O R N Z V V E iG S Y N D R O M E
Nassen-Korn/weig syndrome is characterized by atypical
pigmentary relinal dystrophy (retinitis pigmentosa albe­
scens In some cases], night blindness,, spinal cerebellar
ataxia (Friedreich's type), celiac syndrome, acanlhocyto-
sls. low serum levels of cholesterol, triglycerides, and fat-
soluble vitamins, extinguished EiRU, and abelalipoprotein-
en fe .J5Cuil&_^J6 Abnormalities of exlraocular movements,
including ptosis, strabismusr nystagmus, and progressive
ophthalmoplegia, have been noted.-I ?:>
Hassen-Korn/weig syndrome is recessively inherited,
wilh mutations in the gene encoding the large subunil of
microsomal iriglycerlde transfer prole In (M 'lP) on 4q22-
24. M (tJ acts as a chaperone that facilitates the transfer of
lipids on lo apofS.Llil ApoH-100 is an essential component
of very-low-densily lipoproteins and low-denslly lipopro­
teins (LDLs). Аров-4й is secreted from the intestine and
is needed for the assembly and secretion of chylomicrons
by the intestine.'0, The patient can assimilate fat into the
intestinal mucosa, but a defect exists in its removal from
this site because of the deficiency of plasma chylomicrons.
Jbe liver and the retina become depleted of vitamin A.
Ibe role of vitamin A deprivation in causing the retinal
degeneration in ihis syndrome is supported by observa­
tions (hat large doses of vitamin A have produced return
of dark adaptation thresholds and electroretinographic
responses.112' l^rge-dose vitamin E supplementation com­
bined wilh low-fat diet and soluble vitamin supplemen­
tation appeared lo prevent the retinopathy in one small
uncontrolled sLudy.11 Studies have shown prevention of
the neuro logical and relinal degeneration to a large extent
if water-soluble vitamin A, Er and sometimes К supplemen­
tation is begun before age 2:"' Some progression
may still occur, and reversal of changes does not occur.
 The pigmentary retinal de-gene™Lion in these patients is
often associated with waxy pallor of the optic disc, attenu-
aLion of [he retinal vessels, periphery] ring scotoma, and
E#£ atrophic changes associated with clump or spot pig­
mentation rather than bone corpuscular pigmentation.
The retina[ degenerative changes were milder in two broth­
ers with the syndrome seen at the Bascom Painter bye
Institute (I'igure 5.74). One of these brothers has main­
tained excellent visual ["unction while being given 25 000
LiniLs o f water-soluble vitamin A for 20 yeans [figure 5.741:
and F], lie recently noted progression of nyctalopia to the
point that he had to give up driving. Jfis serum vitamin A
levels were low. After treatment with 50 000 units o f vita­
min A, the serum levels of vitamin A returned to normal
and he experienced marked improvement o f The nyctalo­
pia and some improvernent in the l:HC.
Histopalhologicallyr Lhere is widespread loss of pho­
toreceptors and abnormal L3AS-positive granules in the
j.fj :u , |/[erlron microscopically the RPE contains
abnormal amounts о flipofuscin and lamellar inclusions."'''
F A M IL IA L
M Y P O B E T A L IP O P R O T E IN E M IA
Kiimilial hypobetalipoproteinemia is a distinct entity
from the llassen-Kornzweig syndrome.-11J6 jl-U [t is a
dominantly inherited disorder characterized by low total
plasma cholesterol levels and low levels of LDLs, I lepalic
vitamin A transport is normal but vitamin В transport
is severely affected due to lack o f LL>L Patients may be
asymptomatic or may have a variety of neurologic defects
ranging from psycbomolor retardation to polyneuropa­
thy, mostly attributed to lack of vitamin E. An atypical
form of pigmentary degeneration may occur in homo­
zygous patients. A patient with heterozygous hypobeta-
Lipoproteinemia developed night blindness at age 51
years and ophthalmoscopic evidence of severe progressive
retinal degeneration before she died at age 75 years,L|J"
Histopathologic examination o f her eyes revealed absent
photoreceptors and massive deposition o f basal linear
j .7 4 Basse п-Ko m zweig synd ru in e .
A - D : 7lus 2 1 -year-old man iIb hi^h myopia and his brother
had mild bigjnentary reLinai dy-tLrophy, HiiretalipoproLoin-
en'.ia, MtigresSive spinocerebellar degenerating, Lrernor,
a-Lanthocylosis, and с ф а с syndrome. Th-L'i г paTents Were fi rs-l
coLJsiпя. His visual acuity W a i 20/40 in bolh еуен w hen he
wan ]nilially Examined, B is fundi shewed paraoenlral and
patchy peripheral zones o f depigm enlaJion of lhe retinal pig­
ment epjlhulium (R^L) and m inim al na-rrowin^ of the relink I
vessels ■A —[ J i. An eleclroretino^rana r e v e le d hli^hlly abnor­
mal rod and conn funtLion. His acuity was unchanged until
age 3 2 years. AL age 4ft years his visual at uity had declined
La a/100 ri^hL eye and ii/200 left eye. He had bull's-eye тп.эс-
ulopalhy. There was no nyclalopia and modejaLe tonslric-
Lion of the peripheral visual fields. Thu peripheral fundi wure
blottd and free of pigmentary migration.
E and F: His ID-year-old bnolber showed similar but less
severt! pi^menLarv changes in addition to a prominent angi-
oid slreak :arrow, E) and a blond ["undus peripherally. A
lar^e, flatr scalloped, hypopi^nienLed lus-ion in lhe periph­
ery ol one eye was probably hypertrophy ol the R PE 4FI. His
visual acuity was 20/25 in the right eye and 20/40 in the left
eye. Hes electroretinogram in the right eye was normal and
in the left eve showed modera1e3y abnormal nod anti cone
ne^ionses. H e took vitamin A, 2 5 0 0 0 unils dally. There was
minimal change in his visuaJ function and fundi w hen exam­
ined al a^,e 4^ years. During lhe following 2 years, hfbVEfvcr,
he developed moderately severe nyctalopia that responded
favorably lo 5 0 0 ( 5 0 unils of vitam in A daLJy.
it nnd I-, ^[lurlun; uf 3>r. knhn I f lynn.i
deposit and jninimal migration o f pigment epithelium
into the retina. Vitamin t supplementation, along with A
and K, caii limit Lhe neurological and relinal degeneralioLt
if begun early and maintained lifelong.^"
N E U R O L IP ID O S E S
Lhe term "neurolipidoses" is used to describe the iteuto­
nal storage diseases. Iltese can be divided into two hroad
types: (1) the sphingo lipidoses; and [2] the nonglycolipid
neuronal storage diseases, or ceroid lipofuscinoses.
fwt'imylipiihac* 40
Sphingolipidoses
lhe sphingolipidoses are lysosomal metabolic disorders
Involving conjugated derivatives of ceramide wilh phos­
pholipid or sugars 110 Specific catabolic enzyme deficien­
cies are responsible for abnormal accumulation of normal
cell constituents. Demonstration of Lhe enzyme deficiency
makes iL possible Из detect heterozygoles [carriers) so I hat
prenatal counseling can be provided." In some o f the
sphingolipidoses, abnormal accumulation of lipids within
Lbe retinnil ganglion cells causes opacification of these cells
and results ophlhalmologically in the so-called cherry-red
spot macular lesion [E'igure 5.7SA-CJ. 'Ihe sphingoiipido-
ses that may be associated with a cherry-red spot include
the following types.
G angliosidosis
lhe Л-hexosaminidase system consists o f two major
isoenzymes, ;5-hexosaminidase A [<* - ;)) and
.l-hexosaminidase R ( l - (3) as well as one minor isoen­
zyme,. jj-hexosaniinidase S ['"■-'*). 'Ihese isoenzymes are
formed by the different combinations o f the two subunits,
tv and i. The (\ subunit is encoded in the M K A ' A gene
located on chromosome 15q 23-24 and lhe l subunit is
encoded in Lhe НИХ 8 gene located on chromosome 5q
13.У. A defect o f the .] subunit leads to total absence of
bolh ^-hexosaminidase A and H, and gh^es rise to Sandhoff
disease, while a defect of lhe subunit results in 'lay-Sachs
disease due to (he absence of г■.-hexosaminidase A and S.
Storage in Tay-Sachs disease Is mainly in the central ner­
vous system, whereas in SandbofFs disease storage is abuLi­
da nt in the liver, pancreas, kidney, and other tissues. 'Ihese
two diseases present an identical ophthalmic and neuro­
logical clinical picture" i2 lMh but organomegaly and skele-
Lal abnormalities are seen in additioLi in Sandhoffs disease.
G.'Wj G an gliosid osis, Type i
Tay-Sachs Disease
Although patients appear normal al birth, by approxi­
mately (s months they manifest blindness, irritability, and
psychomolor deterioration that results in death by 2-4
years o f age. Nystagmus, cherry-red spot, and poor vision
are prominent early (l:igure 5.7I5AJ. The cherry-red spot
may fade or disappear shortly before death due lo loss
of ganglion cells: it is accompanied by progressive optic
atrophy. Occasionally corneal clouding and endothelial
changes can be seen.Ji:37,ll3e In Tay-Sachs disease there is
a selective deficiency of the A component of hexosamini­
dase, whereas it] Sandhoffs disease there is almost total
absence of both (he A and В components of hexosamini­
dase. 'i’he pathogenesis of 'lky-Sachs disease is attribut­
able to the accumulation o f GM2 trihexosylceramide due
to defective i hexosaminidase A enzyme, caused by muta­
tion in the alpha subunit o f the hexominidase A gene on
chromosome 15q(lj. СЛ12 trihexosylceramide accumu­
lates predominantly: in retina! ganglion cells whereby ret­
ina becomes turbid with milky-white coloration and the
э.7л Sphingolipidoses^
A: Cherry-ned spoE in an infant w ith Tay-Sachs disease.
B: HisEopalhology Ы retina in Tay-iachs disease showed
marked loss and disruption o f IheganyEion cell Eayer. Special
stains far fat showed fat w ilh in [he remaining .ganglion Lei Is
Kis well as within Ihe inner relink I layers.
C: Election micrograph showed lysosomal bodies di-s­
Iended w ilh Га mingled uphingolipidK within a gAiigtrai ce([
[X 200001.
D -F: Granular whiLe niricula haio lesion 'Li asso( ialed w ilh
N i итп л п п-Hie к disease lype tS in a ti-vear-old gt.H w ilh nor­
mal intelligence hepalosplenomegaJy (D), and normal visual
K U ily , NoLc lipid-1л den madtippbagES in boiie m,irrow 'h .
G - l: Granular white m acular halo (C ) first detected at aye
1 1 years in a 43-year-oEd paEienl w ith peripheral poEyneurop-
л Ih^1
. 2 0/2 □ visual acu ily bilMStatEy, associated wi'.h sea-blue
[H!Stiqtytasi5 ■l-Ej. Electron micnuscopy revealed slriking coE-
Ieel ion of heterogeneous material stored in cells of various
types (l}_ It was most prom inent in endoneural fibrubEasCs.
The appearance of lhe stored material was mosl like I ha I
seen in Niem ann-Hick disease. Ttie patient's older sisler had
simitar findings. Both patients w ere otherwise healLhiy.
1C; Г ю п > V . i r i i J l l . i r i d F E l t e 11 D -F , O w n |- E ,jr^ r:r ■L'i ; i l . IIJ I. 1 ■ 1Ч7Б.
A m L r i c . i i M t s d lL llI A im e t a C ia n . Л И r c H u r v c c l . C i- 1 , и з U t i n y Of
U r. t l u r c lo n К л г и -.. t> r A l ) ^ tA W j№ n c c I . Ih e U<.'l i r i . i l A ll as,
Svju iv J l1f i i d 1 0 . fc .lO S l
cherry-red spot. Gangliosides are most plentiful in the gray
matter with most o f the clinical and pathologic manifes­
tations occurring in the nervous system. The commonest
form is the infantile form, as described earlier, with death
by age 4. A juvenile form with later onset and slower pro­
gression is also known. The mildest form o f the disease is
the adult subtype, also called late-onset lay-Sachs disease.
Manifestations include ataxia, dysarthria, muscle weak­
ness. and dementia, in this form, no cherry-red spot is
seen, as the amount of accumulated ganglioside is smaller,
lhe last variant is the chronic form, with patients surviving
well into adulthood, ihere are approximately 7S described
mutations, although the majority o f patients have the
infantile form The diagnosis is confirmed by assaying
the activity of individual i hexosaminidase isoenzymes
in serum and cultured cells of patients. Tay-Sachs is most
common among Ashkenazi Jewish children
Substrate reduction therapy that uses small molecules
lo slow the rate of glycolipid biosynthesis shows efficacy in
mouse models o f Tay-Sachs. linzyme replacement therapy
and gene substitution hold promise for the future.
G M j G angliosidosis, Type II
Saiidhofr's Disease
The clinical presentation is similar to Tay-Sachs with
similar neurological and ophthalmic features, including
seizures. An infantile and a late-onseL form are seen clini­
cally based on the nimount of accumulated gangliosides.
] Eepatosptenomegalv is present, lh e disease is autosomal-
recessive and has been seen worldwide and is not panicu-
lar to Ashkenazi Jews.1
N iem ann-Pick D isease
N iem ann-lVk disease, an аutosomal-recessive disor­
der, has been subdivided into five types differing in their
clinical manifestation, age o f onset., severity of neurologic
involvement, anti genetic background.11+|-lM? All have in
common a deficiency of sphingomyelinase enzyme or iso­
enzyme. Macular changes have been noted only in types
A-C.
']Vpe A (infantile form] of Niemann-[]ick disease is
the most common and most severe form. It is o f particu­
lar interest to ophthalmologists because o f the occurrence
o f cherry-red spot in at least 50% o f cases, mild corneal
cEouding, and brown granular discoloration o f the ante­
rior lens cortex or capsule, 'Ihese children have a clinical
course similar to lhal of lay-Sachs disease. The visual loss,
however, is delayed because o f preservation of the gan­
glion cells, '['his results in a less well-defined whiLe opaci­
fication that extends farther into the periphery and persists
in Niemann-Pick type A disease. Fifty percent of reported
patients with this autosomal-recessive disease have been
Ashkenazi Jem. Ilepatosplenomegaly, progressive neuro-
degenerative features followed by death in infancy ensues.
]Vpe В is a non neuropathic form o f Niemann-EHck
disease that occurs in patients with normal vision, hepa-
tosplenomegaly, byperlipidemia, interstitial lung disease,
and variable survival to adulthood [ligure 5.75L>-K). A
brownish-red foveola surrounded by a granular gray halo.
Less prominent than the typical cEterry-red spot, may occur
in some patients (figure 5,44E ) . 11 Cogan
et aE. coined the term "macular halo syndrome' to
describe this ringlike perifoveolar distribution of crystal­
loid opacities.; The macula has multiple layers of gan­
glion cells and I he foveola is devoid of ganglion cells.
Lipid storage in die multilayered ganglion cells results in
the grayish-white macular halo. I h is finding is presen t in
several of the lipid storage disorders, including'Iay-Sachs,
Sandhofrs. ЩЛ2 gangliosidosis, galactosialoidosis. and о
neuraminidase deficiency.11''
Figure 5.7SG depicts a macular halo that occurred in
two siblings who were in good health until middle life
when (hey developed moderately severe peripheral poly­
neuropathy associated with sea-blue histiocytosis, absence
o f foam cells typical o f .Niemann-Pick disease, marked
depletion of sphingomyelinase activity in leukocytes and
cultured skin fibroblasts, and electron microscopic evi­
dence of a striking collection o f heterogeneous material
stored in cells of various types in a biopsy of the sural
nerve. Storage of material was most prominent in endo­
neural fibroblasts in the form of electron-dense inclusions
with some suggestion o f lamellar structure; dense inclu­
sions containing numerous vesicular or vacuolar struc­
tures. often with fine electron-dense floccular material
centrally: structures with a concentrically arranged lami­
nated appearance; structures having the appearance o f
Ь.7 6 Ga uche r Js d isease.
A-D: This 54 -year-old W om an with Ihe aduii form «I
Gaucher'? disease bad a splenectomy at ID years o f aye.
Except for hi Iакта I hip replacement for degenerative jo ml
disease, her цепега! heallh was |^ood. ^Kc* had prom т и п I
yd law p^ngiMclJral aL the n a iil and temporal linnbus o f bolh
eyes. Visual acuity was 20/2 0 in I he ri uinI eye and 20/30 in
the left eye. Note (he variably sized w hite d eposit, some of
which ant; anLerior [(] the гиГiПчТI vessels scnllejed thrdtlghuui
Lhe fundus, Relatively few small lesions were* present in the
m acular area larntjw.. Dl.
E and F: Sim ilar w hite lesions in [his 6-year-old boy w ith
Ihe U$fa nti ijaj Ю г т of G ailch ft's disease. HislopaLho logical I v,
the I ti-si (]л-5 w erti caused by clusters of Foamy m acro p h ig te
iasterisk: on Ibe inner г*?Г iпйнI иигГлсе.
Galaclosralidosi-s,
G and H : tlherry-nod spu5 in ,i 2 1 -year-old wom an w ilb the
cherry-red spot-myoclonus syndrome. She had a slowly pro­
gressive neurologic disease characterized hy reduced visual
acuily,. nystagmus, dysarlhria, ,итН m yoclonic spasms. A sister
was sim ilarly affected. Angiography was normal except for
slij^hl bkiTring of detail^ of m acular capillaries 441.
I: Histfcpalhalojjit fin d in g in the maculat area of a 22-year-
old wom an w-ilh bilateral cherry-red spols, generalized
Irum or, muscular weakness. convulsions. and mental dele-
;i oral ion. The eyes w ere oblainud aL aulopsy following death
from bronchopneumonia. Note that Lhe ganglion cells in the
m acular region are enlarged and contain an eosinophilic
[iranular inlracytoplasmic malerial with eccentric disfjlace­
ment ol the nuclei. Special stains revealed periodic acid-
5chitf-posi)ive, diasLase-resistanl material in the cyloplasm of
the ganglion cells. The material in the ganglion cells stained
positively with oil red O , Luxol Iasi blue, anil Sudan black.
Slams for acid mucopolysaccharides, w ilb and wjlhout hyal-
uronidase and Iron stainsr were negative.
ib nraJ к Iruni UmO 1Л al.11>:; 1. fmhl h ml.1*L’■
myelin debris; and из me mul til animated structures bear­
ing a resemblance to zebra bodies. Although the appear­
ance o f the stored material most closely resembled that
seen in \iem ann-Pick disease, the clinical picture and
bone marrow biopsy findings were unlike any of the vari­
ous forms o f Niemann-Tick disease.
Type С Niemann-l]ick disease occurs in non-Jewish
patients and is a milder, chronic form o f the disease that is
characterized by normal early development but later pro­
gressive psyehomotor deterioration and death between age
5 and 15 years. There is moderate visceral and central ner­
vous system involvement. Some patients have vertical oph­
thalmoplegia. the cherry-red spot is less prominent and
granular in appearance, similar to Lhat in type H. Visual
acuity is usually within normal limits. Histopathologic
and ultrastructural studies of eyes with type С Niemami-
Pick disease have shown variable degrees o f lipid storage
in the ocular tissues." 2 " 1
fwt'imylifihhtSL'* -4I 3
 Variable degrees о Г psychotic behavior including aggres­
sIon and sexual disinhibitionr and mild to moderate cog­
nitive dysfunction, are seen in some individuals. The
disease Is inherited as an autosomal -recessive trait and
results from the deficient activity of lysosomal hydroSase
acid: sphingomyelinase (A Shi) enzyme with subsequent
accumulation of sphingomyelin, lhe phenotype is vari­
able; the exact reason for Lhis is not well untiersLood. EL is
likely that environmental or unknown genetic factors In
addition lo (he various mutations in the ASM gene may
contribute to Lhe phenotypic heterogeneity. 1L5|-]|54
Landing's D isease (G en eralized CM :
G an gliosid osis, Type f)
landing's disease is a lethal inborn error o f metabolism
caused by a defect in the ensyme beta-galaclosidase A,
И. and с..'- uC'^ ’llC'(' It is characterised by decreased psy-
cliomolor development, hepatosplenomegaly, cherry-red
spols in approximately ^Q^i] of paLienLs, and corneal opac­
ities. ihe disease is classified as a mucolipidosis because it
combines both clinical and biochemical signs o f a muco­
polysaccharidosis and a sphingolipidosls.
F a rte r’s D isease (D issem in ated
Up ogran uloma tosis)
ГагЬегЧ disease is a lysosomal storage disorder character­
ised clinically by hoarseness, subcutaneous nodules, pro­
gressive arthropathy: retarded growth and development,
lyniphadenopathy, visceral and neural involvement, and
occasionally fever.11 l ] " Death usually occurs In patients
between G and IS years of age. Ocular manifestations may
include a mild cherry-red spot in the macula.1 ' 'Jhe accu­
mulation of ceramide is characteristic and is secondary to
deficiency o f lysosomal ceramidase. Hislopalhologically,
there is an accumulation o f a gjycolipid within the retinal
ganglion cells. 1 Uitrastmcturally. intracellular inclusions
and structures similar to other sphingolipidoses have been
described." 4
Meta chrom atic Leu kodys trop hy
Mclachro malic leukodystrophy.- an autosomal-recessive
disorder, is caused by a deficiency o f sidfalase A., a lyso­
somal hydrolase. Hie resulting lysosomal storage of
metachro malic glyco lipids (mainly su Ifat ides) and degen­
eration o f myelin are responsible for the progressive
mental retardation, dementia., hypertonia, ataxia, convul­
sions spastic quadriplegiar and death that usually occur
In infancy.11w' 11 Optic atrophy and., less commonly,
perifoveal retinal grayness or a cherrv-red spot mav
occur,L]fr0
Gauchefs Disease
Gaucher's disease is a hereditary autosomal -recessive
disorder o f lipid metabolism characterised by the accu­
mulation of sphingolipid gjucosylceramide in the reticulo­
endothelial organs, especially the spleen., liver, and bone
marrow. Infantile (type 2) and chi Id hood/adolescence
forms (type \ and 3) of the disease have been described.
The infantile form is characterized by progressive psycho­
motor deterioration beginning at about 6 months o f age.
with death occurring before 1 years of age. The adolescent
form of the disease is more common and is character­
ised by splenomegaly, anemia, thrombocytopenia, bone
!esionsr lung features., aortic valvular and ascending aor­
tic calcifications, and conjunctiva] pigmentation. Age of
death In the adolescent type is in early adulthood; how­
ever recenL ensyme therapy has prolonged life expectancy
in these patients.m::
The evidence for cherry-red spot maculas occurring in
(his disease Is questionable.11:1' Scattered, discrete, while
spols distributed in (he posterior fundus, especially along
the inferior vascular arcades situated in the superficial retina
or on its surface, ha\T been described In three cases (Figure
5 . 7 6 K ) . Similar spots were seen at the llascom
Palmer Hye Institute in a patient wilh the adolescent form
of the disease (f igure She also had very promi­
nent pingueculae that have been previously reported in
(his sjfndronHiL,( " " " While spots similar lo ihose appear­
ing in the retina occurred in the peripheral cornea, in Lhe
anterior-chamber angle, arid at Lhe pupillary margin of tw&
adult brothens.J 11,11 fight and electron microscopy revealed
tbal these white spots in the fundus are caused by clumps
of macrophages distended by numerous mem bra ne-
bound vacuoles containing tubular structures identical
lo these cytoplasmic bodies of Gaucher's celts observed in
other organs such as the spleen, liver, bone narrow, and
the central nervous system (Figure 5.76К}.,]<' ;' IN'r>':i u One
Taiwanese Woman with relinal va&cular leakage and macular
edema wilh subsequent alrophic changes in Lhe macula has
t>een described. lfJ' Demonstration of glucocerebnosidase
deficiency in white blood cellsr fibroblasts, or histiocytes is
required for diagnosis* because there is so much overlap in
lhe clinical signs with olher diseases.IM,Ll "10,1 Rnzyme ther­
apy with infusions of mannose-terminated glucocerebro-
sidase has helped reduce the visceral and hematological
manifestations.L "■
M U C O P O L Y S A C C H A R ID O S E S
l he mucopolysaccharidoses ли a heterogeneous group
flf inherited diborders in which a deficiency pfafr jfifczyffljje
leads Lo interference wilh the degradation o f dermatan
sulfate, heparan sulfate, and/or keralan sulfate, result­
ing Ln accumulation of glycosaminoglycan Ln lysosomes.
Lhe associated system Id manifestations are variably and
depend upon the type of mucopolysaccharidosis. Tjiese
include hepatosplenomegaly, coarse facies, skeletal dys­
plasia, mental deterioration, cardiorespiratory abnormali­
ties, and eventual early death. ОсШаг changes in some
of the Lypes include corneat clouding (types \ and 2),
pigmentary retLnal degeneration, optic disc edema. glau-
co ma, and optic atrophy.11,1 1176 E^lgme n Cary re LInal degen-
eralion occurs in the following mucopolysaccharidoses:
mucopolysaccharidosis 1 (HuFler's disease), mucopoly­
saccharidosis 1-S (Scheie's syndrome), mucopolysacchari­
dosis 1-1 ]/S ( Hurler/bcheie), 2 (Hunter's disease), and
mucopolysaccharidosis 3 (Sannlippo's syndrome).1' '
Mucopolysaccharidosis 1 is characterized by the defi­
ciency o f alpha-i-iduronidase, the enzyme responsible
for hydrolyzing the terminal <*-L.-iduronic acid residues
of dermatar arid heparan sulfate at Lhe 4pl6.3 locus.1' a
Ophthalmoscopic evidence o f the presence of retinal
degeneration in patients with these disorders is often
minimal. Kundus abnormalities include pseudopaplll-
edema, papilledema, macular edema-like changes, and
mild pigmentary disturbances, 'h e eleclroretlnographlc
abnormality common lo ail Lhree types of the mucopoly­
saccharidoses Was the pattern of rod-cone dystrophy, with
rod amplitudes being more affected than cone ampli­
tudes."'' I listopathologic and ultrastruetural examina­
tions have demonstrated variable degrees of outer retinal
damage that is similar Lo that found in retinitis pigmen­
tosa. ' J-,lh’ Mucopolysaccharidosis type 2 (Hunter)
patients may develop exophthalmos due Lo shallow OFbits
and secondary papilledema and optic atrophy PatienLs
with mucopolysaccharidosis lype G (Maroleaux-L.amy)
can develop corneal clouding, papilledema, and glaucoma,
but pigmenLary retinopathy has nol been described.1' ' ' l [ ''
JridocilLary cysts have been seeEi in one patient each
wilh bcheie and Maroteaux-Lnny syndrome.1" ' 1, Stored
material showing fibrillogranular and multlmembranous
inclusions may be found in many o f the ocular and body
tissues in these disorders and is nol diagnostic o f a specific
mucopolysaccharidosis, f urthermore, similar structures are
found Ln the olher storage disorders, including lhe sph in-
go] rpi doses and m u co lip id o ses.' Therefore, further stud­
ies such as skin fibroblast culture and enzyme analysis are
required for specific diagEiosis.
Successful bone marrow transplantation can aller the
biochemical and some of the systemic manifestattons o f
these disorders, and there is preliminary evidence to sug­
gest that it may result Ln partial clearing of comeal cloud­
ing, resolution of optic disc edema, and stabilization o f
retinal function, " :,й
M U C O L IP ID O S E S
3he mucolipidoses ate ал autosomal-recessively inherited
group o f lysosomal storage diseases that share some fea­
tures with die mucopolysaccharidoses, including Eiurler-like
facies, shorl stature, skeletal dysplasia, hepatosplenomegaly,
and dysostosis multiplex, but do not have excess mucopoly­
saccharides Ln Lheir urine."''' :l" ihis clinical phenotype
is a feature o f the earEy-onset forms of sialidosls (muco­
lipidosis I), as well as l-cell disease (mucolipidosis EE) and
pseudo-J Eurler poiydystropby (mucolipidosis III). I wo dis­
orders added later to the mucolipidoses, lhe cherry-red spot
myoclonus epilepsy syndrome {sialidosis type I) acid muco­
lipidosis EV. differ in that the facial appearance is normal
and they do not have skeletal dysmorphlsm.
Kozyme deficiencies have been identified in mucolipi­
dosis i, II, nmd Ш and lhe nomenclature has been changed
as below." Transport of newly synthesized lyso­
somal proteins Lo lysosomes is Impaired due Lo a genetic
defect of the Colgi enzyme uridine diphosphate jtJD P)-
jV-acetylglucosamine: lysosomal enzyme N -acetyl glucos­
amine 1-phosphotransferase. ihe basic molecular cause
o f mucolipidosis JV Is nol known but linkage analysis is
underway Lo Identify1 the chromosomal map position of
Lhe defective gene. Precise diagnosis o f these autosomal-
recessively inherited diseases depends upon radiographic
studies for skeletal dysplasias, analyses o f urine for sialy-
Ioligosaccharides, morphologic studies of bone marrow
acid skin biopsy specimens and enzyEnatic determinations
o f sialidase and Ш>] ■-/V-acetyIglucosamine: lysosomal
enzyme JV-acetylglucosamine-1-phosphotransferase.
Mucolipidosis Type-1 (Cherry-Red Spot
Myoclonus Syndrome; Sialidosis, Type 1}
lhe cherry-red spot myoclonus syndrome Is a slowly pro­
gressive autosojnal-recessively Inherited sLorage disease
caused by a lysosomal enzyme deficiency of neuraminidase,
'lhe early-onset form o f the disease is a severe progressive
disorder characterized by onset before age 2 years of Hurler-
like facies, hepatosplenomegaly, delayed development, cor­
neal clouding, visual loss, op Lie atrophy, cheny-red macular
spots, and cataract. fl The late-onset form becomes mani­
fest in children 7 years or older. It affects non-Jewish indi­
viduals and is compatible with a long life 1155' 1136 Its features
Include cherry-red spot maculae, resting and intention
myoclonus, nystagmus, mild to moderate reduction of visual
acuity, and normal intellect." )T Hgure 5.76 [C3 and
EiJ deptcls an example o f the late-onset Lype. Et shows the
cherry-red spol and angiographic findings in a patient who
was seen at the Bascorn I’almer Eye Institute in 156S"'11, and
who, together with her sister, subsequently was shown lo
have evidence of storage of sialidated glycopeplides and gly-
co lipids caused by a deficiency of the enzyme alpha-N -acetyl
neuraminidase.1’...... . Yonl reported the histopaLhologic
findings In an adult patient with cherry-red spot maculae
who jnay haw had this syndrome (figure 5.761).ljK"
Mucolipidosis 3(Stalidosis, Type IE)
Patients with mucolipidosis 3 have, facies resembling those
tn J in tier's syndrome, skeEetal abnormalities. and often
tow beta-gaEactosidase activity. Myoclonus is less promi­
nent. Many of the patients are mentally retarded, and
some have corneal and lens opacities and are deaf. Almost
all have cherry-red spots. Many patients are lapanese.
Mucoliprdosis Type II (ML II Alpha/Beta,
1-Cell Disease)
Clinical findings present at birth include Hurler-like facies.,
bulbous nose, and thick doughy skin. Mnear growth stops
at age I year. Progressive joint stiffness, dysostosis multi­
plex, recurrent respirator}- infections, and congestive heart
Failure lead to death by 5-Й- years o f age. Corneal cloud­
ing and glaucoma may occur. A characteristic histological
feature is the presence o f enlarged lysosomes filled with
undigested compounds in patient fibroblasts, also called
inclusion or [-celк 'Ihe affected gene is GNFTAB 12q23.X
Mucoliprdosis Type 111A {ML IEE Alpha/
Beta, Pseudo-Hurter Polydystrophy)
Patients with mucolipidosis type Ell develop the onsel during
the first Few years o f life o f joint stiffening mild facial coarse­
ness, stature below third percentile for age, kyphoscoliosis,
and X-ray evidence of dysostosis multiplex similar to that
seen in the mucopolysaccharidoses with the amis and hands
most prominently affected 'J:5' I hey have a milder form of
M L II alpha/beta. The disease stabilizes after SS years of age
and patients may live up to the eighth decade; Patients may,
however, have aortic insufficiency. As a result o f an enzy­
matic defect there is an excess intracellular storage of acid
mucopolysaccharides and gjycolipids that are apparent ultra-
structurally as fihrillog^attular inclusion bodies and membra­
nous lamellar vacuoles, respectively. Corneal clouding and
hyp егоpic asLigmatism are constant ocular features. Retinal
haziness; surface wrinkling retinopathy, and optic disc
edema may be present. They may have a relatively mild reti­
nal dysLrophy.1 1 lji:l ihe affected gene fe G N P lA S ]2ql3.3.
Mucolipidosis 11IC (M U II Variant, ML EEI
Gamma)
Jhe affected gene is C N lTC, I6pl3.3. It has a milder phe­
notype o f the pseudo- Hurler type.
Mucolipidosis Type IV
Patients with type IV mucolipidosis manifest delayed
development, psychomotor retardation, and general­
ized hypotonia soon after birth.1" ' ' Skeletal anomalies.,
hepatosplenomegaly, and coarse facial features are typi­
cally abseilt. Strabismus, corneal clouding, optic disc pal­
lor narrowed retinal vasculature, pigmentary retinopathy,
and extinguished LKG may develop during early life. Light
3.77 Lipofuscinosis.
A -and IJ: This З-уиаг-old white? j>irl com plained of the necenl
onsel (31 poor Vision'. Her isual ac uity in the ri^hl eve W ifi
2CV30 and in the lalt eye was 2 D/40. Note the bull's-eye pat­
tern o1 retinal pigment epi Ihelium iKF’t i atrophy and the
slighllv naTrnwud retinal vessels in (her I of I macula in A and
Iho с<загне m o ilin g of Ihe? RPL in the peripheral fundus in 11.
On1 .1year previously line patienl had been ajJym plom atic. Her
visual aCllHy was and the fundi appeared wilhin nor-
maE Iimils.. AL 7 years of age the patient's visual acuity was
reduced to coum ing lingers in Lht1 righl eve and hand m ove­
ments in the left eye. Al 3 years of age she developed grand
mal seizures and nyMaцд1us. At ;It-.i1 lime she had li^nl per-
ceplion with pour projection Ln both eyes.
С and D: This fl-yoar-oSd brother o f the patient illustrated in
A iind E had first noted vis uni d b h lifairces t year previoutlv.
Visual acuity at that time was 20/50. Visual acuity aL Ihe time
these photographs were made VL-as linger counling in belh
eyes. Note ih e раЭ1ог Ы 'he C&tit disc, marked attenuation
□I Ihe retinal vessels, and cuarue clum p iny of pigment in the
peripheral fundus. Over the subset]ыепI 3 years he devel­
oped further visual loss, jjenera I i ie d seizures, nyslagmus,
dy-sarlhria, and mild dementia.
E and f: Histopalholoyy of the macular region of a child
who died of juvenile EipftfL^sdfiosis. NoLe Ihe marked atrophy
involving all of the reliral layers in the foveal area (E) and
Lhe peripheral macular area IF I of Ihe same eye. N o le loss
of ganglion cells and marked degenerative changes involving
lhe oul-er nuclear layer and receplor plemapts. The-го wure
pigment-laden cells present in lhe outer layers, o f the retina.
and electron microscopy have demonstrated loss o f retinal
photoreceptors, pigment migration into the retina, and fine
granular material consistent with mucopolysaccharides and
concentric lamellar bodies, presumably representing phos­
pholipids, in macrophages, plasma cells, ciliary epilhelial
cells. Schwann cells- retinal ganglion cells, and vascular
endothelium.11*'1 LHC changes in isolated cases include
severely reduced rod and cone-mediated responses and an
electronegative scotopic response.|J0? Patients [both girls)
with a mild phenotype consisting of corneal clouding
alone without neurological or skeletal changes have been
reported. 1307 Ml. IV is caused by mutations in M CO LS3,
which codes for mucolipin-lr a O-amino-acid protein
ill at is a member o f the transient receptor potential fam­
ily/ 'Ihus far. most o f the patients have been Ashkenazi
Jew's and the mutations in them seem to differ from
the imitations seen in affected non-Ashkenazi Jews.l-'"'
G A L A C T O S IA L ID O S IS
(G O L D B E R G - C O T L IE R S Y N D R O M E )
Galactosialidosis is a lysosomal storage disease character­
ized by decreased alpha-neuraminidase and beta-galaclosi-
dase caused by a decrease in a protective protein/calhepsiu
A, an intraly50S0JTtal protein that protects these enzymes
from premature proteolytic processing. '■''' 12,2 three types
ofgalactosialidosis are recognized clinically.
1. Eiarly in fa n Lilt form: presents tieonatally with Elurler-
like facies, dysostosis multiplex, progressive neurologi­
cal changes, progressive visceromegaly, find early death.
Ocular abnormalities are common and felal hydrops
occurs in one-third of cases.1' ' ' '■'ll
2. E.ale infantile form: presents in the first 2 years o f life
with visceromegaly, valvular heart disease, with or
without cardiomyopathy, growlh retardation, dysosto­
sis multiple*.- mild neurological compromise, ocular
changes, and angiokeratomata. The disease progresses
slowly: cardiac management is of primary concern.1" '
3. Juvenile/adult form: found exclusively in |apanese
presents anywhere fro.m 3 years o f age Lo adulthood.
Neurological, caidiac. and ophthalmological features are
prominent with cherry-red spot* myoclonus, and ataxia.
Corneal clouding, decreased vision, coarse facies, acid
arrhythmias can also occur.Ii'1" 1212 lhe cheny-red spot
may fade and be relatively inapparent in older patients.
I lislopalhoEogic and ultrastnictural examination of the
eyes of a 13-year-old boy with lale infantile шгтп revealed
Loss of retinal gang)Ion cells, abnormal accumulation ol" lipid
and protelnaceous material in residual ganglion cells, optic
atrophy, and inlracyloplasmic inclusion bodies in retinal
and amacrine c e l l s . Conjunct ival biopsy in two siblings
with the adult form showed Several types of inlracyloplasmic
Inclusions In die fibroblasts, lymphatic capillary endothelial
cells, bchwann cells, and cpiLhelial cells. Membrane-bound
vesicles wilh fibrillogranular content, dense granular inclu­
sions, and oil droplets were also seen.1'11’-'
N E U R O N A L C E R O ID
L IP O F U S C IN O S E S
llatten in 1903 described two siblings wilh progressive
macular dystrophy and cerebral degeneration, the juve­
nile form of NCL. 'lhe name fa lle n 's disease" should be
reserved for this form of N C L NCL is a Lysosomal storage
disease that Involves the accumulation o f insoluble fluo­
rescent lipoproteins believed to be ceroid and lipofuscin.
pigments normally associated with a g i n g . _ l i " '['he
term "пеигопаГ is misleading, since many different cell
types, including smooth muscle, glands, Schwann cells,
and vascular endothelium, contain the storage prod u ct1'*
Psychomotor retardation, seizures, visual loss, and prenia-
Lure death characterize the clinical features o f this group o f
neurodegenerative disorders.'I’he&e patients can be divided
into four principal groups on (he basis of the age o f onset
as well as ultrastruetural findings related to the deposi­
tion of this aulofluorescent pigment in neurons and other
body tissues, 'lhe mode o f inheritance in these disorders
is autosomal-recessive and genes C LW l-C LN B baVe been
identifi ed.lli2 ~l2U
">. 713 L o n g -c h am fatty acfd d eh vd ro g e n a se d e f i с ie n cy
(LCHAD).
A—I: An almost 5-year-old wa& exa mined w ith a visual acuity
[)E 2 0 /4 0 in each eye and fire pigment mottling through rjul
the fundus HA—Cl I. PhulogTaphs w ere repeated at дде 11 and
13 ( [ H j ) with no apparent Lhange in Lhe retinal appearance.
The patienL had L C H A D deficiency. She was maintained on
a low-fal carbahvdr;lie-rich diet and showed na prtitof£s5ive
chorioretinal degeneration. O ptical cohefence tomo^raplw
showed clioroidiai ^ha-rrtm-in^ Irom the increased foveal reLi-
naf pigmum up iI helium pigfrt^nt [H and I .
iCaUrtesy tjl Dr. M:Lh.k l ■i I i ri -
Infantile Group (CAN/, Haltia-Santavuori
Type)
infantiIe-group patients manifest microcephaly, severe
neurologic and visual symptoms usually before 2 years of
age. Enfan tik -onset NCL is caused bv mutations in a pal-
mitoyl-protein thioeslerase 1 gene, CLJV1, located at]p32.
Late Infantile Croup (C L N 2 , Jansky-
Bielchowsky Type)
Jhe onset of severe neurologic disease, including ataxia,
seizures. loss of speech, and regression o f developmental
milestones., begins between 2 and 4 years o f age and usu­
ally precedes the visual symptoms, ihese patients typically
have a rapid progression of the disease, resulting in coma
and death within a few years, [.ate infantile .NCL is caused
by mutations tn a pepstatin-resistant peptidase 1 gene,
CLN2r located at 11p i 5. Up to 3 5 % o f these patients also
have an approximately 1-kb deletion in the CLflJj gene
located at 16pl2. which coties a hydrophobic protein of
unknown function. CLN5 at 13q3]-32, Ci.,4'6 at ]Si\2]-23f
and CJ.M7 and al Sp23 are associated wilh certain
variants of late infantile NCI..
The Juvenile Croup [C L N 3 , Spielmeyer-
Sjogren Type)
Juvenile group patients, resulting from the mutation of
CJ..M3 gene at ]6p]2. who constitute the major subgroup
of these disorders, typically are seen initially in child­
hood at a peak age of й-7 years because of visual symp­
toms, which are often advanced. Mental disturbances, such
as loss o f recent memory, tantrums, speech disturbances,
and inability to learn, may be present at the time of pre­
sentation but are often overlooked; londoscopic examina­
tion may reveal very mild changes in the RJbL. -Soon Lhey
develop signs of a bull's-eye type of macular atrophy, fol­
lowed by progressive alterations in the RPE throughout lhe
fundus together wilh narrowing o f the retinal vessels and
optic atrophy [f-'igure j L77A^D).l2i5 Fluorescein angiogra­
phy is helpful in detecting the early signs of the disease.
Klectroencephalograpby and electroretinography are useful
in making a correct diagnosis before the onset o f definite
neurologic symptoms.1'" " ''''4l' ' 11 Diagnostic findings in
the juvenile type include vacuolaled lymphenries in the
peripheral blood; rectal biopsy ultrastructurally Shows
fingerprint forms intracellularly in neuronal tissue, 'Lhese
patients experience progressive neurologic symptoms,
including seizures, With a peak incidence of 1-2 years after
the onseL of symptoms, tremors, ataxia, dementia, and
paralysis, resulting in death usually by 20 years of age.
Histopathologic examination reveals extensive loss
o f the rod and cone cells, outer nuclear layer, and outer
plexiform layer; accumulation o f a PAS-posiliw lipid sub­
stance in the ganglion cell layer; narrowing o f sin all retinal
vessels; and gliosis of the nerve fiber layer (figure 5.77E
and fr).1:230-1213 ^ nQ^e ль &епсе c f дщо flu­
orescent inclusions in the photoreceptors, suggesting lhaL
photoreceptors may he rescued if a therapy for Batten dis­
ease can be developed.1"1'' Changes are more marked pos­
teriorly than anteriorly. Iheie is extensive RFE atrophy and
migration of pigment into the overlying retina, electron
microscopy reveals curvllinear bodies and fingerprint
profiles in the ganglion cells — “f he differences
in retina! pathology of the three childhood forms of the
neuronal ceroid lipofuscinoses are of a quantitative rather
than a qualitative nature.
Kufs Disease (Adu]t Neuronal Ceroid
Lipofuscinosis)
Kufs disease is the rarest form (l.i5-10%J o f lhe neuro­
nal ceroid lipofuscinoses and is autosomal -do minanl in
inheritance. Cerebellar, extrapyramid aI, and motor signs
predominate. Visual failure is infrequent. M ild central
visual and color deficiency and impaired smooth pursuit
have been noted.l -i'' Seizures are rare, and lhe patients
are often demented. Two clinical phenotypes, type A,
wilh progressive myoclonic epilepsy, and type B, with
progressive dementia, exlrapyramida! symptoms, sup ta­
bu Ibar and cerebellar dysfunction, are known, lhe under­
lying molecular defect in Kufs disease (C LN 4) is still not
known. tie d ton microscopic examination of the
peripheral blood lymphocytes for characteristic "finger
profiles." single membrane-bound intracyloplasmic vacu­
oles, and osmiopbilic granular bodies is a sensitive means
o f delecting palienis with any o f lhe four forms as well as
the carriers.12111
Long-Chain 3-Hydroxy-Acyl-Coenzynne
A Dehydrogenase (LitHAD) Deficiency
Fatty acids are metabolized within lhe mitochondria by
beta4?xldalion by the LCHAD enzyme. Deficiency o f
LC H A D resulLs in bypokelolic hypoglycemia, hepatic ste­
atosis, card iomyopa thy, and rh ab do myolysis, in addition,
peripheral neuropathy and retinopathy occur ]deficiency
of LCEfAD is a severe disease that usually results in death
during the first 2 years o f life unless the natural course can
be modified by a low-fat, high-carbohydrate diel Death
is usually due lo hepatic or cardiorespiratory failure.
Children who have been diagnosed early and have been
maintained on a low-fat, high-carbohydrate diet show
ocular findings.
'I'he ocular findings in a large cohort were classified
into four stages.1' En slage I, the retina appears normal
at birth. Soon after pigment dispersion occurs al the reti­
nal pigment epithelial level {stage 11) (Figure !>.7i3A-C).
Palcby chorioretinal atrophy, progressive occlusion of cho­
roidal vessels and choriocapillaris in the posterior pole
follows, resulting in deterioration of central vision, oflen
with relative sparing of the peripheral fundus [I'igure
/5.7Й1: and C ) (stage III). Central scotomas and posterior
st^pbyioma develop in slage IV. Developmental cataracts,
which are flaky opacities around the nucleus, progressive
myopia, and deterioration o f visual fields and color vision
are the finding? o f LCHAD deficiency. fcKG abnormalities
and chorioretinopathy precede the development of myo­
pia and posterior Staphyloma.1: il
3:luorescein angiography in the second stage onwards
shows poor choroidal filling and progressive loss of cho-
riocapiHaris. Subsequently, dropout of choriocapillary
lobules occurs with large areas o f chorioretinal atrophy. hi
late stages, Lbe laige choroidal vessels are preserved mostly
temporal to the macula. Color vision and dark adaptation
are affected by stages Lt-LtL il is possible that derange -
menL of the ЙРЕ and choriocapillaris is the primary defec!
in this condition, and the photoreceptors1 ' function is lost
secondarily, ihe fundus changes in stage HE onward resem­
ble central areolar choroidal sclerosis, progressive bifocal
chorioretinal dystrophy, choroideremia, and pathological
myopia. En the early sLages, it resembles a carrier slate of
choroideremia or rubella retinopathy with fine pigment
mottling [t-'igure 10.50). Both night blindness and diffi­
culty wilh central vision eventually occur.
lhe condition is inherited in an autosomal-recessive
fashion wilh a C152SC mutation in the gene o f lhe
LCHAD enzyme.' ' I:i' 13J" lhe treatment is early rec­
ognition and management with a low -fat and a high-
carbohydrate diet, and survival up Lo aye 31-plus has been
noted.lZAi
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retrftE ngmerMa. to,1J ^ lld m a 1Kfr 113:1fi1 -4
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625. H.fi't'Sl G Daieb'et. Sarstlia \ Я^Н ягаэд ав deletion retilsqfttojrepean; r: FlEPi
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Macular Dysfunction Caused by
Retinal Vascular Diseases
diseases affecting primarily the retinal arteries., capillar­
ies, and veins or any com b u llio n o f the ihnee may be the
underlying cause of central vision loss. Angiography pro­
v id e r information concerning alterations in retinal blood
flow, the normal retinal vascular pat t e n a n d retinal vascu-
Ear permeability. Jn addition, in the sensory retina, which
normally has ve ry little extracellular space, stereo angi­
ography provides а means of pictoriallv defining expan­
sions of the extracellular space produced by extracellular
fluid accompanying alterations In vascular permeability
and cellular destruction. Optical coherence tomography
(Q C T ) has enhanced the ability to define these lesions in
a vertical cross-section and three-dimensional layout, far
a more detailed discussion of the basic pathopbysiologic
and histopathologic changes occurring in retinal vascu­
lar disorders and their correlation wilh fluorescein angio­
graphic and biomicroscopicchanges, the reader should see
Chapter 2.
R ET IN A L V A S C U L A R A N O M A L IE S
A variety of minor anomalies of the retinal vascular tree
occur commonly and are unassociated With visual morbid­
ity. Some of the vascular anomalies, h oivever. [nay cause
visuaE loss.
Hereditary Retinal Artery Tortuosity
IJecurrent macular hemorrhages occurring in family mem­
bers with congenital arteriolar Lortuosity constitute a rec­
ognized syndrome (figure 6 .i)lA -C ).]' lr Visual loss in
these patients may occur spontaneously or following rela­
tively minor trauma (see the discussion on Valsalva maoa-
lopathy, p. 730 in Chapter Sj. Kelinal arterioEar tortuosity
may increase with age, particularly during adolescence.
Jhe tortuosity affects primarily the second- and third-
order retinal arterioles in the macular area and the veins
are spared. Fluorescein angiography has failed to disclose
any primary alterations in the retinal vascular tree that
would account for the predilection for hemorrhages I he
pathogenesis is unknown. Despite recurrent bleeding-
vision usually returns to normal, Itotinal bleeding during
scleral buckling procedure has been reported.'1' ЗЪеге is
no evidence that a systemic hemorrhagic diathesis is pres­
ent in patients with this disease, which is inherited as an
autosomal-dominant trait. Families With increased nail
bed capillary tortuosities- carotid aneurysm, and micro­
scopic hematuria have been described. i' ' - > Con genital
retina] arteriolar tortuosity must be differentiated from
other diseases associated with acquired retinal vascular
tortuosity, including polycythemia, leukemia, dyspro-
teinemia, sickle-cell disease, famiEiaE dysautonomia.
6.01 Re гnull vase ula r ano mal ies.
A - t.: Congenital n.'tmal лПепд! tuTtuosiiy and spontaneous
macular hemorrhage in a 2 6-year-old man who сI-eveloped
Foss o f central vision in the righl eye w hile weight-lifting. He
had had a similar episode? in Eioth eyes previously, tnuh lime
the hemotfhaifES и lea reel and jte regained 20/20 acuity. He
was df Eastern Ьишрщлп {JescenJ and had two palcrnal first
cousins with I he к а т е o cular problem.
i.^-F: Congenital reLinal aHeria loop in an asvmptumalic: Ejcjy-
G-l: CongenrLal retinal arterial rnalformalion in a young
nsymptomalic wom an w ilh 2 0 /2 0 visual acuily.
I—I : Congenital venous loop in an asymplomittic young
woman.
| A - t . u o u r t e iy o ! D r . О и г м Ы I. I V A i u i l o . i
]nucopolysaccharidosis VI, and Kabry's disease. Pulsatile
three-dimensional arteriolar tortuosity, previously
reported in patients wilh coarctation o f the aorta* rarely
occurs now because o f early surgical intervention.
Spontaneous retinal hemorrhages may occur in multi­
ple family members in the absence of related systemic dis­
ease or retinal arterial tortuosity
Inherited Retina] Venous Beading
Meredilh described five affected m embers in two genera­
tions with sausage Iike beading o f the major retinal veins
and conjunctival venules, focal retinal infarctions, altered
retinal vascular permeability, and in some cases abnormal­
ities of arteriolar and venular distribution.11 E.arge venules
crossed the horizontal raphe in some cases. Three mem­
bers had retinal and/or optic disc neovascularization and
vitreous hemorrhage. Some members had renal disease
{Alport's disease) and decreased leukocyte counts. Stewart
and Critter reported four affected members o f two genera­
tions with retinal venous beading bu( no conjunctival ves­
sel tortuosity.1 The affected members had low to normal
neutrophil leukocyte counts that differed significantly
from unaffected members.
Retinal Venous Tortuosity in Infants
Neonates born to mothers who smoke during pregnancy
have a higher incidence o f venous dilation and tortuosity
arteriolar straightening and narrowing, and intraretinal
hemorrhages. I his is likely the result o f a combination of
higher hematocrit and higher peripheral vascular resis­
tance in these babies. All vascular changes correct by age
6 montbs.]<* Infants with congenita! heart diseases show a
higher incidence o f retinal vascular tortuosity [ 4 mor e
so those with cyanotic heart disease, low hematocrit, and
low oxygen saturation.-7
/irffrfHil Vam'u 1лг. mvl^ies 4.59
Congenital PrepapiHary Vascular Loops
Imitated loops in v b m n g fitffir lhe veins or the arteries may
occur in and around lhe op Lie nerve head (figure 6.0 1
D-L).-11 l.oops involving the retinal arteries are more
common than those involving veins (4:1].J| Retina E arte­
rial loops may arise on or near lhe optic disc from a major
branch retinal artery, the central retinal artery. or a cilio-
retinal artery (Hgure (S.01 JJ-F). Jhey extend anteriorly into
the vitreous., are composed of one or more Lwisls,. and usu­
ally supply one o f the retinal quadrants. 'Ibe loops often
exhibit movement within the vitreous and casl a shadow
on lhe surrounding fundus. 'Ihey may pulsate. They occa­
sionally occur bilaterally, may be familiaE, and may be
partly surrounded by gliaE or fibrous sheaths.-1- Retinal
circuш Lion lime in the affected quadrant may be slightly
increased, '['here is a high incidence of cilioretinal arteries
in these eyes, and they often supply much of the retinal
circulation.Jl A small percentage o f these patients may
Eose vision secondary to occlusion of lhe arterial loop
(Hgure vitreous hemorrhage
amaurosis fugax,-'1 and hyphema.*1 Thrombosis or twist­
ing of the loop probably causes the obstruction (Jigure
6.02Л-С). Histologically the artery comprising thE loop
is o f normal structure."1'i'he pathogenesis of the vitreous
hemorrhage occurring in and around these loops is uncer­
tain but probably is caused by rupture o f small vessels
near the base of lhe loop caused by its movement.
P re papillary loop with branch retina] artery
occEusion.
A —G : This 17-year-old fem ale developed a sudden temporal
field defect in Hilt lefL eye. Shu li^id л liihtury of sickle-cell
trail but was- otherwise normal. Her visual acuity was 20/25
in each eye. A prapapillary loop emanated from Lhe disc
along with retinal opacification in [he upper nasal quadrant
necondarv o f a branch relinal лКегу to occlusion within the
loop. Ttie retinal color recovered in 4 weeks but the visual
field defect remained. Thrombotic ucdu sion of 1he torn-
mu meat ion 1rom !hc loop to the £цреГопази bijlaidl relinal
artery was noled (artow).
Congenital macro vessel
H - J: A 34-year-old m ale presented with a 3-year history
d I type 2 diabetes. Visual acuity was 2(У15 in both eyes.
[Jilalu d fundusi examination of lhe ri^h! eye showed а Злг^е
mitcrovessel Ltjursin^j the m acula. The mat-roVessel w as a
V4iin and the angiogram showE^d it draining into lhe supero-
temporal vein aflfit crossjng the htJiizonlal raphe and 3at-
eral to Ihe fovea and dipping back inferior to (he fovea and
rucrosibinft nasal to lhe fovea.
l A - C i , 4. c i u г l i n y C Ji- l - r . u i t c j H r ' L c l n n : H - l . Ггш п . i l l h ' r l ■| r i i i I lI
iv ilh [s c m u ^ M o n Ггснп fm n rA . Н г А 1 м ± г 'c '. i n n u . i j - i. L . u v r c i i L 'i r I. t h e k L 'lin .L l
Al l.i!-. S.iuiyiLW 2UI0, ^7e-D-7CJ2U-i^2U-1r [Л.ЗИ4.1
Congenital prepapillary venous loops (figure 6.011-1,)
and macroretinal vessels should be differentiated from
acquired dilaled venous col lateral channels caused by
retinal venous obstruction (see E'igure S.-Sl] and K) and
meningioma o f the optic nerve (see I'igure ] 5.16).
Congenita] Retinal Macrovessels and
Arteriovenous Communications
A large aberrant retinal yesscL more often a vein than
artery; may extend from the optic disc into the central
macular area, where it typicaSLy sends tributaries across
Lbe horizontal raphe (I'igures 6.021]-] And 6.03 A-E).'ujL
In some patients.. both an artery and a vein are affected.
Visual function is usually normal. Fluorescein apngiogja-
phy typically shows no permeability alterations but may
show small areas o f capillary non perfusion and focal cap­
illary dilations [Ensure 6.03C and L>]. In some cases the
capillary bed separating the dilated artery and 4rein may be
normal (ligune 6.0211-J). In others there is a direct arte­
riovenous anastomosis [Kigure 6 .0 3 b-G ].1-' Changes fit
blood flow or permeability within these communications
may precipitate loss o f visual function (Hgure 6.0ЗА and
11, and H-G) and are reported following bungee jumping,
ihese malformations typically occur uni laterally in single
or multiple sites. I here is a predilection for involvement
of the papillomacular bundle area and the superotempo-
ral quad r a n t . Both sexes are affected Detection o f the
anomaly usually occurs on routine examination. JJetinal
macrovessels may occasionally be associated with similar
vascular anomalies affecting the conjunctiva and mouth
(fig u r e 6..03J-L). Macrovessels are isolated findings and
should be differentiated from large-caliber retinal vessels
(artery or vein] associated With anomalies such as Goats'
disease, retinal capillarv hemangioma, fajniliaE exudative
fc. 03 C o nge n ila i ret in a Eп и cro vessels.
A and B: .Macular hemorrhage occurring in a 50-year-old
iлап w ild on awakening n o ktl a central srdrtoma c-ausfep by
a гс-LiплI hemOrt+iagC; associated with л congEiniLal macro-
aMery and vein. His visual acuity wan 2ti'4u.
С and D : MicroaneAirysJns lanows) associated w ilh congeni­
tal macnokrtery and vein. There was minim al staining o f the
microaneurysms.
E—G : Blurred vibiun uccurred in Ihis heallhv w ilh m ac­
rovessels associated with an g io ^ ap h ic evidence o f arte­
riovenous shunting (arrow, FI, and hypoperfusion of the
juxtafeveal relinal capjllary nelworli iC ).
H-L: Conjjenftal retinal macrevieins (arrows, H and If asso­
ciated w ilh macTovensels ctf the conjunctiva Ijj and the dor­
sal ■К I and Central side fL) of Ihe longue in an apparently
hcallhv ®l-yeaH>1d man. Comp u led I omography 01 Ihe brain
revealed multiple venous a noma lie*..
LC лгк; I). [ U L ir f L 'jy ■
:-I I Jr. !. S. (Julian .
VEtreoreti пора thy (l-'LYR], ittconlinentia pigmenti. and
other peripheral vascular occlusive diseases.
iietinal arteriovenous anomalies have been subdivided
into groups, depending on the severity of the anomaly.= l i-1'1
Archer's group I comprises patients with retinal macro ves­
sels with interposition of an arteriolar or abnormal capil­
lary plexus between the major communicating artery and
vein, ihese well-conipensated arterivenous communica­
tions rarely extend to involve the papillary vasculature and
are rarely associated with cerebrovascular malformations.
 l*atients in group 1 demonstrate clirt^ct arteriovenous
communication;; without the interposition of capillary
or arteriolar elements (figure б Л ^ )^ 1,34-32 lliese dilated
arteriovenous communications, sometimes referred to
as artietlovenoiijB aneurysms or racemose aneurysms* may
be single or multiple. Leaking macroaneuiysms occasion­
ally develop on these enlarged vessels (t'igure й.04Ь).:’1
Angiography demonstrates a short dye transit time but
usually no evidence o f e\Lravascu3ar leakage." d| The
neighboring microvasculature may be alteredr and there
may be beading and multiple fusiform dilations of Lhe
Eaige-vessel walls. Capillary nonperfusion or an absence o f
capillaries may be evident in the neighborhood o f major
vessels. These arteriovenous communications typically
remain stationary. In some cases decompensation may
occur and cause hemorrhages (figure 6.04f and G ]j focal
areas of estravascu!ar ejtudaLion and perivascular scarring
(b'igure Ш 1 ); and neovascular glaucoma. 1 11 Occlusion
o f a portion of or the entire malformation may occur
(E'igure й.041> and E* and IE and 1}.
^.04 Retinal arteriovenous malformation.
A - t : This 2 2-year-old asympLomalic м тлп had 20/20
visual acuity bilaterally. The lefl eye was normal. She had
no evidence o f е к м о с Щ а г vascular malformations. Note
the artsridVetipUs comm uni cal ion in thy macula i.A^ and
focal vascular sheathing and scarring in I be- periphery : В I.
Angiography demonstrated lhe arteriovenous com m unica­
tion j and minim al slain mg tinly in the area o f the periva-s-
cular scarring.
D and E: Ttiis 14-year-old gtrE had 20/20 visual acuily w hen
first examined. Angiography at 14 seconds showed prompt
fill inn al Ihe superior arteriovenous anom aly LL>. Tvto yearC
laler she E>:perjenqed ncule loss of vision in lhe eye. W h e n
seen 9 monLhs later, her visual acuity was 20/300. The optic
disc was swollen (Ej. Sh-Liathing of some o f lhe large retinal
vessels and pigmentary abnormalilies in Ihe m acula had
occUrr&d. Angiography revealed perfusion of Lhe relinal arter­
ies, increased retinal circulation Limer and л w indow defect
in Ihe macula, all findings suggesting partial occlusion of Lhe
vascular anom aly and previous submacular exudation.
F and G : This teenage girl was asymptomatic and had nor­
mal visual fu n d ion w hen lhe arteriovenous anom aly was
dlfecftvenkJ (R . She had no exlraocular vascular malforma­
tions. Several years later she noled a paracenlral scotoma in
Lhe right eye caused by spontaneous bleeding from the vas­
cular anom aly nasal lo the oplic disc fC).
H and I: Arteriovenous malformations in lh e macula (H) and
periphery of the right eye and lhe maxi! a n 1 bone of ibis girl
were discovered afLer the experienced severe bleeding dur­
ing a denial ejttracLron. Surgical ligaLion o f the ipsilaleral
carotid artery was required Iо conlrol Ihe bleeding, Soon
afterward there was sponlaneous occlusion o f the m acular
arteriovenous aneurysm (I).
|-L: Gross photograph and photomicrographs o f an arterio­
venous aneurysm with arteriovenous anaslomosis (Arrovl^ J
in a rhesus monkey. Fluorescein angiography showed no e v i­
dence o f ini ra retina I staining. Nole lhe enlarged retinal ves­
sels LhaL encroach on the surrounding retina iK and L). The
dilated spaces in the inner nuclear and oulur plesiform layer
w ere free of proleinaceous esudale and apparenllv con­
tained a serous Iransudale.
[D a r i d Ё., й й и г Е п у tnl U r . k i o b u r l к i r.i li. :n ir n I . ^ L J i. a v ,jl . i l . ' V I Гго т
г : : ■. 1 9 (6 , Л п ч п г мп M e d ic a l M l i o n . A l l J~ iuhC x r r i M i r v L 'i : ! . I L
■Г "
Г г и т H u r iu c h i c l .il. ; p u b lis h e d w iL h { ж г л и и п п f r o m I t i c Л п к г к а п
l u u r n . i l u f O p l ' . l h . i l i r u l i i ^ y ; f i i f l S r L j t h i l i y I I k : O p h l K i l m i r I i l i ч -l r i i^; C f f J
k-
©
 In group 3 patients [Figure 6.03} there are many anas­
tomosing channels o f large caliber Thai are so inter!wined
and convoluted that separation into their arLerJnL and
venous components may he difnculL. Visual acuity is usu­
al ]y poor. Ophtbalmoscopically and ingiograpb^al!^ the
retina may show perivascular sheathing, exudation, and
pigmentary degeneration, Home eyes may be blind from
hirth. P’atieuls with severe retinal involvement are lhe
most likely Lo have periorbita! or cerebral involvement
СWyburn-Mason syrtdro me).-1 ■’7# M& S2M™
Com plications of these vascular anomalies include inlra-
retinal hemorrhage, aneurysm formation with intraretinal
exudation, retinal artery occlusion, Valsalva retinopaLhy, :
central and peripheral retinal vein occlusions, neovascular
glaucoma, vitreous hemorrhage, arterial macroaneuiysm,.
and macular hole [Figure 6.G4B, t, C„ and ])
Severe visual loss caused by occlusion of the malforma­
tion occurs infrequently (Figure 6.04D and F). Slow visual
Loss may occur because of mechanical compression of the
optic nerve.*1" Spontaneous regression of the lesions may
occur occasionally^11 lhe histopathology of arteriovenous
communications identical to those seen in humans has
been described in rhesus monkeys (Figure 6.04]—E_).: ' 4'
Anomalous arteriovenous communications should be dis­
tinguished from those acquired secondary to peripheral
vascular occlusive disease [see figure G.ttll and tv).""'
Photocoaguiation treatment may occasionally be
warranted in those patients who develop exudative
maciilopathy.i1
For a discussion of congenital retinal telangiectasis and
retina] vascular hamartomas, see p. 514 in Chapter 6 and
Chapter \ 3, respectively.
б.(l Re Irnal a rter iovenous malformat io n .
A and B: Ths 16-year-old fc-n 11•.= was seen Гог intractable
headaches jand migraine w ilh лига. H e r vision was 20/15
in each eye. She had several anom alous vessels emanating
from the disc and peripapillary area. 5iome of lhe I a r^er-ca I i-
ber vessels appeared lo com m unicate with the choroidal cir­
culation ajs they dipped into Ibe substance ol" the relina w hile
lhe others; w ere pari of a network of vessel;; seen on the disf.
and superficial peripapiJjarv retina. She had had агг inflam­
matory workup, w hich shew ed m inim ally elevaited angioten­
sin-converting unA'me. Vla^ndic resonance imaging MKI
df lhe bead did nol reveal other ifttjffcnatous (ocj. She was
treated m edically fur headaches and mi prairie.
C—F: This 23-year-old m ale w ith cuunt-rinjjers vision in Lhe
ri^hl anrl 20/20 vision in Ihe left eve complained of several
episodes of headache for the past 2 years. He had a previ­
ous .MK1 that show ed arteriovenous jra lfo m i^ ib n s in his
brain. A la*^u arteriovenous тттл horn-a Li on simulating a
ot" worms was seen in Ihe righl fundus involving lhe vessels
on lhe disc and in lhe m acula associa Let! w ilh dilated and
tortuous reLinal arteries and veins extending up to Ihe periph­
ery. O n e Iflr^e vessel lhal dipped into lhe retina communi-
CnVin^ with the choroid showed w hilenin^ of ilu w all (C iind
Ff. Fluorescein angiogrant showed rapid filling ol the malfor­
mation, making il difficult to determine if the majority o f Ihe
vessels filled from Ihe choroid or from Lhe retinal side - they
Eifcely filled simultaneously from Lhe choroid and retina (□
and I:!. He was trealed iynnptomalScal I у lor lhe migrainous
headache.
Retinal capillary hamartoma.
It- K : This 34-year-old male noled meLamoiphops-ia in his
righL eye for a le w months. A 2 X 2 disc diameter sublie e le­
vation farrowsl was noted in his I'ii^hL eve jus I temporal to Lhe
lovea associated w ilh cysloid swelling of the temporal fovea
(G). An angiogram revealed deep dilated рГениз of vessels
with several bulbous dilatations in the inner relina i I and Jf.
The anom alous capillary plexus leaked with fluid accum u­
lation i-nlo cystoid spaces IK.. The tnalmrmaticfti appears lo
be an isolated hamartoma of lh e relinal capillaries wilhoul
an astrocytic com ponenl. There was no evidence of hamar-
Lomnis elsewhere in lhe eye от body ihus ruling out Luberous
sclerosis.
I A ..n n F H-. n j u r l c s v :>Г I J r . I-1,t in e , к L n H 'i i i , t j - K , c j o u r l r i s 'y ■i: ]> r. I X i \ i( i
Welhbtig.!
Anomalous Foveal Avascular Zone
Controversy exists about the development of the fovea!
avascular zone (HA2); one Jichool believes the future EAX
is initially vascularized.. and by a process similar lo apop-
tosis the capillaries are lost lo form a capillary-free ione.
Absence of ihe E'AZ and multilayered foveola seen in reti­
nopathy o f prematurity [ROE1) is explained by this theory " :
lhe other school studied seven retinal whole mounts aged
between 26 and 4] weeks'" gestation and found a blood ves­
sel-free zone in all retinas, including at the 26-wee к gesta­
tional age.1"1'Ihis ring Was open temporally at age 26 weeks
and closed by 37 weeks' gestation lo form a complete cir­
cle. il is believed that the superior and inferior blood ves­
sels grow faster than the horizontal raphe and the nasal
vessels grow faster than the temporal ones, resulting in the
open temporal ring till about the 37-week gestational age.
ihe diameter o f ihe FAZ gradually decreased in size from
500 pm at 35 weeks to 300-350 pm at 40 weeks. After birth.,
the accelerated retinal growth stretches the foveat pitr mak­
ing it wider and shallower; this remodeling o f the fr\Z con­
tinues to occur even up to 15 months to eventually yield an
I'AZ that is 300-750 |im in size.
It is likely various factors influence formation of the
fovea I vascular zone during development: astrocytes., mac­
ular pigment, ganglion cells, vasoemJothelial growth factor
(VliGHj levels and their alteration in hypoxia, to consider
a few.^'^' Whatever the insult that allows blood vessels to
invade the future fovea I pit during development (figure
6.06), this in turn likely prevents normal foveal piL for­
mation, resulting in a multi hive red Ibveal center (1'igure
6.06b, Fr K, and Lj. Eiypoplastic fovea with small or absent
6.0b Absent foveal avascular zone fFAZ) and toveal pit,
A—F: This 40-year-old m ale had л hi-sLcwy of "jum ping eyes"
with subnormal vision since childhood. W h e n his son was
e vaIилled for nysla^mus al a^e 6 mftnths, he was sen! in for
a reli na consulLiilion Lo f>E.hlp find a diagnosis ["от Ihe infanl.
He was best corrected to 2Q/bO in each eye Л rnoder-
ately high m yopic refractive error. He was nol atbinotic.
Tht! tu ndus hud a blonde coloration w ilh orange color a I
the posterior pole. Л fluorescein angiogram showed no spe­
cific a b n o rm a lly Due Го Ihe myopia and lighl fundus back­
ground.. я good perfusion of ihe Lovea vascular pattern was
nal oblainable. Scanning through Lhe entire m acula, a fovea I
depression could nol (re found on oplical coherence Югпоэд-
raphy IE and Flf bu^geslin^ arrcsled foyjEal devel op m ел I as
the cau-se of the subnormal vision and nystagmus.
C-L: This 16-yea r-oEd girl could only be corrected to 2El/25
all thfough her refractive evaluaLionii for lhe previous [0
years. Her color vision was full b ilaterally and she had ли
nystagmus. The righl eye had an anomalou-s architecture of
the reliriril arteries w ilh two branches eacJ> supplying Lhe
superior and inferior posterior pole 1GK The left eye's archi-
Leclure appeared within- Lhe normal Variation I HI; Careful
examination of Lhe fovea and its angiogjam revealed possible
small foVeaJ avas-cuLir zone. tJp lic a l coherence tomography
Lhrough lhe fovua could ncfl localise the Loveal pi1 in either
eye IK. and I.), confirming Lhe arrested foveolar developmenl
as a plausible cause of Lhe subnormal vision.
I G - L , CLIU r l r j i v III U r. I , i n i : t ’ L . I ,m - I
hAZ associated with multilayered foveal pit on O C I is
a feature o f albinism, chiasmal misrouting,1'' ЕЮ ft and
aniridia. IL is likely we will discover more developmental
vasculopathies and other disorders that harbor a multilay­
ered foveal center.

O B S T R U C T IV E R ET IN A L A R T E R IA L
D IS E A S E S
Ш с й ^ а Ь ^ й Л у , diseases may cause obstruction o f
Lbe retinal arLerial blood flow, primarily through one or
a combination o f Lhe following processes: ( I ) embolism;
(2) vascular narrowing; (3) thrombosis: (4) arterial spasm;
(5) vascular narrowing caused by exlravascular disease;
and (6) reduction in blood tlow caused by carotid or oph­
thalmic artery obstruction, lowered syslemic blood pres­
sure, or elevated intraocular pressure.
Embolic Obstruction
Obstruction of the retina] circulation may be caused by7
emboli derived from within lhe human body [endoge­
nous em boli} or front without (exogenous emboli).
En d o gen o u s Em bolization From the Major
Arteries an d Heart
bmbpli derived from ulcerated atheromatous plaques in
the carotid artery, occurring either spontaneously or dur­
ing manipulation o f the carotid artery during arteriogra­
phy or surgery, are probably the most common cause of
major retinaE arterial occlusions (higures 6.07-G.10)
Other Important sources of emboli are diseased or anoma­
lous heart valves. Lmbolization from the heart may occur
spontaneously or during open-hearl surgery or coronary
artery angioplasty.85_йе Patients with embolic occlusion
usually experience sudden monocular loss o f vision, litis
loss may be antedated by episodes o f transient loss o f
monocular vision Easting 1-2 minutes (amaurosis fugax)
in 20-25% of cases, and transient ischemic attacks in
approximately 5-10% o f cases.e’J rl"he average age o f onset
o f symptoms is approximately SO years. ]:ewer than 10%
o f occlusions occur in persons under 30 years of age.^-'4'
Occlusion is more common in nten than in women. In
all, 50-75% of patients over 40 years of age with retinal
6r07 C e n tra l re tin a l a r te r y obstruction ^
A—D: Central relinal artery obstruction occurred 1 w eek
a flew replacement of яп aortic and itiitral valve |Ъг rheu­
matic heart disease in a 55-year-old man w hose visual acuity
consisted of Мцhi percep!ion only. Note Lhe L'herry-ned Spot
and ^boxcnr^ formation of blood in the retinal Vessels iA .
A n d m a p liy shows marked retinal л Мету obstruction and
relrojjrade filling of proximal rd ii:al veins via I h oplic disi
col lateral circulation iL3-l?l.
E and F: Central relinal artery obstruclion in a t E>-year-old
wom an. Angiography show к fluorescein leakage from peri fo-
^TEal arterioles.
G —I: Central retinal artery obstruction and retinal hemor­
rhages in a 2У-year-okl man w ilh rheum alic mitral valvular
disease and subacuLe bacterial endocarditis. Note I be cherry-
red spoL, "b o x car1' formal ion, and angiographic evidence of
marked increase in relinal с ire Ltl a L i o n lime.
|—L: KiLchy retinar ischemia and delayed perfusion o f both Lhe
retinal and choroidal circulation caused by ophthalmic artery
obslni-cti<m in a 73-year-old hypertEri$ive man with ullrasono-
Epaphic evidence ot thyroid ophthalmopathy. He experienced
sudden almosJ complete toss of vision in lhe rijjht eye several
weeks before Lbese phoLojjraphs. H e noted partial return of
peripheral vision soon afterward, Angiography m o w e d Lhal
dye appeared in lhe chtjroid aL 2 ] seconds and in Ihe cenlral
retinal arlery at 15 seconds iK and 3. .
artery occlusion wilE have clinical evidence of carotid
artery disease.''1 '■ In younger patients the emboli are usu­
ally derived from heart valves damaged by rheumatic fever,
congenital anomalies o f the heart valves and great ves­
sels. or prolapse o f the mitral valve (Bartow's syndrome)
(figure C't.07t—L) ,-s :: Most patients with central retina!
artery occlusion (CFtAQ) will have a smaLl area o f pres­
ervation o f light percept ion caused by the presence of
small cilioretinal arteries fl:igure 6.LlSL> and K, arrow].’’"
En patients with no light perception, the physician should
look for evidence of abnormalities of choroidal and optic
nerve head circulation. " ' '
QbsmfdHur R e tin a l. irtfrin l DzprtiS^s -4^ I
 If retinal artery obstruction is incomplete ant] of short
duration, only a slight gray ha^e may result; and little or
no permanent damage to the retina may occur (iigure
б.ОУСг and H j;,. ,9R If Lhe block is more complete, progres­
sive whitening nind swelling o f the inner half o f the retina
develop (figure 6.07A and H). 'these physical changes are
caused by denaturaLion and breakdown of the normally
transparent intracellular prole in, an increase in the intra­
cellular water, and, finally, complete cell al i t necrosis
(figure 6.101).'"' 00 Acute ischemic w hilening of the retina
is a more accurate descriptive term for this change than
retinal edema, which is best reserved for retinal thicken­
ing secondary lo the accumulation o f serous fluid escap­
ing front retinal capillaries inlo the extracellular space,
producing multiple cystoid changes in (he outer retinal
Layers. Acute ischemic retinopathy may be localized
(cot ton-wool patch], as in small arteriolar obstruction, or
more diffuse, as in obstruction of the central retinal artery
or one o f its major branches. Intensified retinal whitening
along the peripheral edge of ischemic areas that cut across
nerve fiber layers is related to the damming effect of the
orlhograde and retrograde axoplasmic fld w JDI
Patients with visual loss caused by acute retinal artery
obstruction usually seek treatment in the first week
after obstruction and show a variety o f clinical pictures,
depending on the portion of the retinal, arterial tree
involved. In central retinal artery obstructionr widespread
ischemic whitening of Lhe retina occurs, except in the fove-
otar area (cheny-red spot), whose blood supply is derived
from the choriocapil laris (figures 6.07A and 6.08G), and
except in some patients in whom focal peripapillary areas
are supplied by a cilioretinal arteiy. Absence of lhe с berry-
red spot in patients with С RAO should suggest the pres­
ence of choroidal vascular ischemia as wet].1" ' hi some
patientSr particularly those wilh chronic systemic hyperten­
sion, transient obstruction o f the central retinal arteiy- may
produce a peculiar picture of multiple gray patches of reti­
nal whitening simulatitig that seen in furtscher's retinopa-
Lby (figures 6.07|-L see figures 6.2311, and 6.25[j. Ihis
pattern is probably the resull of regional variations in arte­
rial perfusion that occur normally or that are the result o f
formation of collateral pathways o f retinal capillary flow
caused by foca] narrowing o f the origin o f the tirst-order
arterioles in hypertensive patients. She visual prognosis in
patients showing this pattern o f retinal whitening is rela­
tively good.' ' '
llranch artery obstruction may be overlooked or mis-
Laken for other disease processes, particularly if lhe patient
Cenlral retinal artery occlusion (CRAOl wilh
n eovasc u la rization о f d isc.
A-F: This 6fl-year-old hypertensive diabetic wumar with a
hijtOry of tind-sta^e renal disease presumed wil-h light per­
ception vision in her right eye. Tlie posterior pole was opaci­
fied and [he blood column in лII Ihe retinal а гй п й ^ and
some of lhe vein*; were fia^men led 'A). A Liny corkscrew
vessel was present cn Ihe optic disc. A small zone of retina
adjacent Lo thy 5Llperalemp6r$ edge of Lhe disc appeared 1o
be perfused by a cilioretinal artery. The left eye had scattered
microaneurysms and dot hemorrhages Irom diabetes Ш|.
Four weukh IdCer she was found lo have a vrLreous hemor­
rhage, bleeding from the corkscrew-shaped vessel seen pre­
viously un the disc i.С and Ап angiogram showed almosl
no perfusion d( the retina ewcepL lor a small zone Itо т a
ciliorelinal artery :t and FJ. Lc is likely the ischemia second­
ary to iheCKAO Emhaneed lhe pre-exislin^ diabetic ischemia
Lo cause the new vessel lo blued.
G - |: The rijjhL fundus of Lhis m ale patient who presented
With severe headache and sudden Joss of vision in his ri^hl
eye shows opaciftalioti of Lhe relina wilh a cherry-ied spoL
and boHcaning of Iho blood column in Lhe retinal arterioles
(C)i Лл arYgiagram shows poor perfusion ihrou^h lhe cen­
tral retinal arLery fHJ. (laroLid angiogram shows dissecLion of
Lhe ri^hl internal carotid arLery resulting in ihetlRAO if and
|j. A few weeks laler, lhe oplic nerve turned pale. The box-
carrin^ of Ihe retinal arterioles continued wilh regaining of
the orange color of the reLina. The vision renamed aI lij^hl
perception.
К anti L: This 75-year-old male wilh hyfjerc-holesterokmia^
hypertension, and previous history of bilateral carotid end-
arterectomies shown a retinal etnbblus in Lhe superoLemporal
arteriole and opaci fjcal ion of the posterior pole -secondary 1o
a CRAD. There is a small patch of и nopacified orange ret­
ina temporal lo lhe disc from perfusion Ihrou^h a cilioreLr-
nal artery larrow^. Note Lhree cotton-wool spots that likely
predale the С RAO. Optical coherence Lomogfaphy showed
LhlckenSng and opacification of the inner relina and shadow­
ing of lhe photoniceplor layer (l_j.
I t , - 1, ': n u rlL J i v nil L ] i . k u l jt i r l W i t lr .v . , 1 1 1 1 1 I . A Im i, V .in n L ij-^ i L .ii.v rL 'n c t: I.
11ч- K i lm .!l A l3 .ii. $ Й т * И 3 0 1 D, 9 7 3 - 0 - 7 0 2 0 - ^ 2 0 - 4 , | j . 3 » 7 . i
has a central scotoma caused b y obstruction of a cilioreti­
nal artery or other small arterioles supplying most o f the
macular area.-1,..... Varying degrees o f arterial narrow­
ing occur. Segmentation o f the blood column indicates
marked s]owing of arterial flow (figure 6.07A. H, and I).
Often one or more emboli are visible in the arterial tree,
either as a taige embolus at a bifurcation of lhe central ret­
inal artery on the oplic nerve head (figures 6.0У G and H
and 6.ШК and I.) or as one or more emboli lodged al dis­
tal bifurcations (I'igure 6.(Ж>).
 Three major types o f emboli occur. Platelet fibrin
emboli are dull, gray-white- often elongated plugs that are
subject lo fragmentation and movt'nKnL into more distal
artertoHS (E-'igure 6.0У| and K). Jhey may be either single
or multiple and are most often Lodged at a bifurcation.
Cholesterol emboli are often multiple, yellow or copper-
coEored iridescent globules that are most often seen in
Lhe peripheral radicles on the temporal side o f the fundus
(t-'igures G.09E) and 6.1 0 C I:).||1Л:UJ L'hey are often unas-
socialed with obstruction of blood flow. W hen causing
obstruction, cholesterol emboli are usually located near
the optic nerve head. Calcific emboli are usually single,
solid, white, uonrefractite, ovoid or angulated emboli
derived from the aortic or mitral valve (figure 6.10Ar Б, K,
and L], l'hey are usually near the optic nerve head and-
unlike cholesterol emboli, which often disappear in a few
days, they may remain visible permanently. Occult calci­
fied emboli may be delected ultrasonograph Leal Ey at the
level of lhe lamina cribrosa in pntlients i\,Jth L1E1AO and in
some patients who present with ischemic optic neuropa­
thy.1'1 Jhe narrowest site of central retinal artery is where
the arteiy perforates the durat sheath and enters the optic
nerve; any of the three types of emboli can lodge here and
not be v i s i b l e . Occasionally a stream o f emboli may be
present, many behind the lamina cribrosa, hence not vis­
ible. Cholesterol emboli arise primarily from atheroma­
tous disease affecting the proximal carotid artery. Calcific
emboli arise primarily from the aortic valve and less often
the aorta and carotid artery.
I'oeal areas o f periarterial sheathing and focal accumu­
lation o f serum Eipids within the artery wall at the site
o f embolic damage to the endothelium may be evident
rather than the emboli themselves ( figure
because both platelet fibrin and cholesterol emboli are
soft and consequently become rapidly fragmented and
cast into the distal radicles of the retinal circulation, fluo­
rescein angiography often fails lo demonstrate complete
obstruction o f either a branch or [be central reLinal artery
by the time the patient reports for examination (figure
6.0У] and К )."4 likewise, the rapid development of
collateral flow around an embolus obstructing the central
retinal artery behind the level o f the lamina cribrosa may
restore intraocular blood flow Lo nearly nomial Levels soon
after the occlusion, ihe best scenario for im provement in
vision is with occlusion at the entry of ihe central retinal
arteiy into the optic nerver since several pial and intra-
neural collaterals vessels can contribute to filling the cen­
tral retinal artery distaE lo its occlusion..112 In most cases,
however, lluorescein angiography reveals a delayed appear­
ance time and an increased retinal circulation time in the
area o f the occluded segment (figure 6.0УВ) En complete
occlusion o f the central retinal artery1, no dye enters the eye
by the artery, but dye filling the optic nerve capillaries by
Way of the ciliary artery circulation may pass through col­
lateral channels and fill the proximal branches of both the
central retinal vein and artery fig u re 6.U7A-D). In com ­
plete branch artery obstruction the arterial tree may be
t .0l4 Bra n сh re linal a rtery obstrn ctio n.
A -С: branch relinal artery obstruction o f unknown cause
in a 1 Ь-year-old man. N o le lhe oliscu ra Li о n of I be proximal
parL of Lhe obstructed retinal artery lhal sujj^HsLs I be possibil­
ity cif a focal area uf reliniLis and late aL ibe sile of
obslrucLion.
D-F: This 6 1-year-old man- developed sudden ortat; of cen-
Lral scotoma in his ri^hL eye setDftdary Id em bolic obslruc­
Lion of a dlioTeLEnal artery. Note Lhe Ej j S^Ih pi Piquet in Ihe
ciliorelinal arlery and lhe superior branch of" lhe central reli-
naf artery ■:arrow*, D). At'ler 16 seconds there was delayed
perfusion of lhe retina in Lhe region of distribution ol Lhe
ciliorelinal arlery i.D. Several months l.iLur lhe scotoma per­
sisted, bul Ibe reLinal whitening had cleared iJ- . Гh :s- pa lien I
bad angiographic evidence of obstruction of his right carotid
arlery.
G - l: Transient em bolic obstruction (arrow, C l of Lhe fnlerior
relinal arLery. NoLe istbuntic w hilening of I be reLina infe­
riorly. The paLient had an alliLudinal field del eel superiorly.
Visual acuity wan 20/20. Nineteen months JaLer lhe relina
had r e f in e d iIн transparency; and lhe patienl had no field
defect. He lalea developed loss ol lhe inferior field of vision
caused by emboli zaLion of Lhe superior branches o f Lhe cen ­
tral relinal i^rtery (arrow, H and I). Note that perivascular
ciifMnrt persisLs aL the sLLe of lhe previous embolus in the infe­
rior arlery I Hi.
\ and K: Focal atheroma narrows' o f a reLinal arterial bifur­
cation following resolution of an impacted choE-esLerol
embolus. S o le tiie sli^liL narrowing of Lhe arterial w all indi­
cated in Lhe ^ u la g r a iil (arrow, K:.
L: ArterioarLerial anastomosis :n a 62-year-old wom an dis-
Lal lo a pjevious atheromatous embolus in Lhe main Irunk of
the arteriole. She had another tiny plaque a! Lhe Ctjveai end
ol 1be arteriole not seen in fig. Thts patienL had suffered a
central retinal arLerv occlusion On Lhe ri^ht side and subse­
quent v developed another branch retinal artery occlusion in
Ihis eye w ilh loss of a si^nificanl part of her visual lieid. ih e
had a diseased aortif valve and an arrhvLhmia.
ID jnrj L. fmm Giisi.1'1'. 6 19ЧЛ, Anxvic.m Mt-ifi* ,il AiMjei,iti(jn. All
п^Иь ri'btrvtid. к
perfused in a retrograde fashion by neighboring collateral
vessels.11" In most instances an embolus lodged in an arte­
rial bifurcation either on Lhe optic nerve head or in the
periphery is only partly successful in impeding the flow
of lluorescein into Lhe artery distal to the site o f obstruc­
tion. In some in stances Lhe dye seeps by the etn bolus,
and in others it bypasses the embolus by way o f collat­
eral Tow.1"' """■ д significant reduction in flow is usu­
ally demonstrated angiograpbically in either case (E'igure
6.07Л—EI5). KeLinal flow remains depressed even after dis­
solution o f the embolus because of the collapse of the
capillary bed by the ischemic and swollen relinal tissue.
Fragmented emboli may completely plug the paramacular
arlerioles. Ilie dye column entering the partly blocked area
may show a pa item of laminar flow. In other cases there
may be alternating nonlluoreseenl zones Cniused by pack­
ets of erylhrocyles and hyperfluorescent zones caused by
stagnant plasma {figure 6.07D and tlj. Носа! fluorescein
leakage may occur at the site of the obstructing emboli
and less often at sites where emboli have previously
Impacted on the arterial wall (Figures 6.07F and fi.09).1'1.
Failure o f fluorescein to leak from lhe bhwd vessels dis­
tal to Lhe site o f arterial obstruction. even Whert circula­
tion has been partly restored. testifies to the resistллее of
Lhe retinal vessel endothelium lo the effects of Ischemia.
In rare instances massive embolization of the retinal cir­
culation may cause marked d^inagel to Lhe endothelium
o f the major relinal artery segments and produce striking
periarterial dye Leakage. Small emboli frequently observed
in the arterial tree beyond the site o f obstruction and else­
where in Lhe fundus usually show little or no tendency to
alter the How of fluorescein. No staining occurs al the site
of these nonobstructing emboli. Very few patients with
endogenous retinal arterial embolization show angio­
graphic evidence of embolic occlusion of the choroidal
circulation.
Some patients with branch artery occlusion may subse­
quently develop another branch artery occlusion or central
retinal artery obstruction (figure 6.0УС-Е). Patients with
recurrent episodes o f multiple branch retinal artery occlu­
sions are more Ukdy to have a nonembolic cause for the
obstruction. (See discussion of recurrent branch retinal
artery occlusion (Susac syndrome), p. 474 in Chapter 6.)
blectroretinography In eyes with central retinal artery
obstruction reveals loss o f the oscillatory potential and
transient depression of the b-wave with either a normal or
supernormal a-wave. Ihe eleclro-oculograEn is diminished
or absent.
]'he intraocular pressure may he subnormal in both
the affected and the opposite eye in some paLienls With
both branch artery and CEtAOf7 Jlelalive hypolony in
the affected eve suggests the presence o f ciliary as well as
retina] arterial obstruction, 'ihe reported incidence o f neo-
vascular glaucoma after CRAO varies from under 2.3% lo
15% or m ore.'" M,)" J'"Some authors suggest thal it occurs
most ofteci in patients with chronic ocular ischemia asso­
ciated with severe carotid or ophthalmic artery diseaserIJ
whereas olhers have not found this association.'D],]2J
Glaucoma usually develops within 2-3 months, often ear­
lier than occurs with central relinal vein occlusion likely
due Lo the rapid onset of relinal Ischemia, liven rarer is the
development of neovascularization of the disc and subse­
quent vitreous hemorrhage (Figure G.OSD).
During the first few days after retinal artery occlusion,
light microscopy reveals swelling of the inner half of the
retina. The swelling is caused by intracellular edema and
cellular dissolution (l:igure 6.] ( ) ] ) . Histologic examina­
tion 3 or 4 weeks later reveals marked loss o f the inner
retina] layers and preservation o f the outer retinal layers
(Figure 6.101).
The white inner retinal lesions caused by arterial
obstruction should be differentiated from white lesions
caused by: (1} retinitis (e.g., toxoplasmosis, acute multifo­
cal inner retinitis JS; see Behcet's disease, Fig. It. 40 and
11.41); (2) inflammatoiy disease of the choroid and reti­
nal pigment epithelium (R PEj fe.g., acute posterior mul­
tifocal placoid pigment epithellopafhy); (3} ouLer retinal
t. It) Embolic retinal artery obstruct ton.
A: C alcificd embolus; from Lhe JbCjrLic valve гн Indeed in a
bifurcalion of Lhe г-e^Frtal arifelV
15: HisLapathology of a calcified embolus (arrow .
(. : HisLopatliology of -a retinal artery embolus cu n Laining
cholesterol crystals farrow).
D -F: OtreLruclicm f f lfic central retinal iirLery left arrow,
D and arrow and c.iIi„чгу arterius fri^hl arrt^ws, D and
arrows, Hi caused by thnndriraaitb^^j thaL EAelasiasJzaJ from
Lbe hip in a 27-year-old man. His symptoms w ere acule onset
of headache, left hemiplegia, and Lose of vision in Ihe rifihl
eye. L and F show a high maynificalion of tumor obstructing
Lbe central retinal artery and ciliary arteries, respectively.
<=: M ultiple coLLon-wool palches in a pa Lien 1 w ilh fnl embo-
Eisnrtf Associated with mull i pie E)one fractures.
H!: Fal embolus I arrow, i in a relinal capillary.
I: H istopal hoi o^y of acute relinal artery obslruclicn. Note
Ihe swelling of lbe inner half of Ihe retina.
J: HisltspaLhologv showing alruphy of Lhe mner half of Lhe
relina monlbs after retina] artery occlusion.
К and L: Large calcific embolus in the m ain trunk of Lhe
inferior retinal artery coming off lhe disc, resulLing in opaci-
fic.il ion of Lhe inferior half of Lhe retina in Lhis- man with a
diseased aorlic Valve.
Ili, L 4 ju rtt, ! y i j l U r . A n c lr t 'w ^ + i'r ry ; t . L o u r U f s y *>l U r . I.tiu it. K j r f i ;
IJ - h . Ггопч B u r d f r r i л !.1 .(. j . C a ilr iM y оГ L Jr. S i J r t t L. О и . ш н ; ^ 1, Ir u m
M l i ^ . l i i t i n t l Z iir im n ir r n .m ; L. i ■ и м I w ilh p c h in B ir t h io im h u k r .it S,
■' l(* -l l! I b'h ! I j. I: II l[>IL D ( f d j J ( j L i r l j b i ( h r L I J N b u ll .S lk t f i П n r t i n . l . ] I n i r C 'I .i r L ',
N1: SLu:k, JO I [I. [>. ii\ .
whitening frojn choroidal ischemia caused by prolonged
elevation o f the Intraocular pressure [see Figure 3.63); (4)
retinal contusion ( commotio retinae, Beilin's edema); f5)
neoplasia (e.g., reticulum cell sarcoma); and (6) opaque
sub retinal fibrin (e.g., idiopathic central serous chorioreti­
nopathy; Figures 3.03] and 3.04) and L). Fmboll may be
simulated by atheromatous plaques developing wllhm
the arterial wall al a focal site of retinal arteiy endothe­
lial defect, e.g., patients who are prone to develop arterial
macroaneurysms [see p. 454 in Chapter 6) or focal arte­
rial wall damage caused by previous Impact of an embolus,
an immune complex, or inflammatory reaction, e.g., in
patients wilh bilateral idiopathic recurrent branch reti­
nal artery occlusion (see Figures 6.19-6.21); acute retinal
necrosis caused by herpes zoster virus (see Chapter Ш):
toxoplasmosis (see Kyrieleis plaques, and figure L0.22]:-
]■[): chronic uveitis1-1; or neoplasia (see Figure 13.3] El).
inner retinal infarction occurs experimentally after com­
plete occlusion of the central retinal artery lasting beyond
approximately 11/j hours.1" 1 Only occasionally does the
patient who develops an acute retinal arterial obstruction
report for therapy within (he first few hours. Treatment,
therefore, is infrequently beneficial. Nevertheless^ in some
patients with incomplete arterial obstruction, obstruction
due lo spasm, or obstruction o f short duration, the isch­
emic .l^.Kiated with the retinal whitening may be
reversible [E'igure 6.Q9G and II). Even the presence of bio-
mlcroscopic evidence of slow blood flow (rouleaux forma­
tion) does not exclude the possibility of visual recovery.131
QrejjjtfcdHur R e tin a l. i/te n n l DL-casc s -4^ 7
Iherefore, in any patient With a history of occlusion of
21 hours or Eessr therapy consisting o f paracentesis, inter­
mittent massage, breathing of 95% oxygen and 5 % car­
bon dioxide, and administration of acetazolamide may
be helpful.' 1'■ Olher modes of therapy th.it havp been
employed include the intravenous administration оГ vaso-
dHalt)и such as papaverine, perfusion of the ocular circula­
tion by cannulation o f lhe supraorbital arteryr hyperbaric
oaygen, .surgical removal of lhe embolus, and Nd-YAG
laser disruption o f lhe embolus."1'L>i' 1 Kxperimenlal use
o f recombinant tissue plasminogen activator lo lyse reti­
nal arterial thrombi was first reported with retinal arlery
o c c l u s i o n . ' ,!l Most recent, has been the interest in
intra-arleria I tlirom bo lysis by cannula ling the ophthalmic
arteiy via the femoral arlery and injecting tissue plasmin­
ogen activator. I his treatment has a rote if it can he per­
formed within 4 hours o f occlusion. W hen arrangements
for intra-arterial cannuJalion are not possible., intravenous
use o f tissue plasminogen activator in (he correct settings
Lo manage any complications can be tried if the patient
arrives within 4 hours o f visual loss.IJ5-|J,L tven without
therapy some patients will experience a remarkable visual
recovery..1
In the absence o f ophthalmoscopic evidence of emboli
in patients over 65 years of age, a sedimentation rale
should be obtained along wilh an exhaustive review of
systems lo exclude lhe possibility o f cranial arteritis as
the cause qf the occlusion. Auscultation of the heart and
carolid arteries and comparison of die pulsation of the
carolid arteries with Lbe ophthalmic arteiy pressures, either
by ophthalmodynamometry or by finger pressure, are use­
ful measures for determining the source of the emboli.
Transesophageal echocardiography in addition to Irans-
tboracic echocardiography is necessary for delecting mitral
valve prolapse or other cardiiac abnormal]lies such as pat­
ent foramen ovale, endocardial vegelations, and noninfec-
tious masses."^" I "J : All patients should have a medical
evaluation. In patients who are reasonable suigical candi­
dates and who have no other explanation for (he emboli-
Lbe evaluation should include aL least digital subtraction
carolid arteriography, which may demonstrate evidence o f
carolid stenosis and/or atheromatous plaques ipsi late rally
in approximately 50% o f cases.1 147
Normal retinal transparency usually returns 2-3 weeks
after acute retinal arteiy obstruction,- but ihe retinal flow
through the involved area is only partly restored. I his
probably is primarily caused by collapse o f lhe capillary
bed accompanying the postnecrotic atrophy o f lhe relina.
In most cases following central artery obstruction and in
many cases following branch artery obstruction, oplic
aLrophy and some narrowing of the retinal arterial tree
fc. I E Carotid maneuvering during internal carotid
aneurysm embolization causing retinal embolization,
A —}: This 4 2 -year-old wom an underwenE onyx, emboli za­
Lion for an inlerna.1 t^tnoLkl aneurysm on lhe lett sidy. Soon
afLei lhe procedure she com pldined of a "film w ilh spotty
ht ill's" ■
■■
. i i her lift eye*. Hr:r vivid л v. ,ix 2.0/20 0*1 the HpM
and 2№30 on I he* Iof I with з relative afFeSml pupillary
dofeeE. She had numerous- white inLraarleriolar refracLiie
emboli imd batchy areas of иЧтл1 whileniitj^ more so in
Lhe lumpoml periphery of" Lhe left eye (A—t , Ci). Angiogram
revealed paLchy choroidal and relinal arteriolar l<]lin^ w ill:
Iale Wedge-shafted hyperfluorescence o l iht! lemprjral rel­
ina sin u la lin ^ Am alric's I nancies. The Lrian^ular area-s of
byperfluorescence w ere secondary lo choroidal ischemia
from occ. I li яion of lai^e choroidal vessels. Her vision spon­
taneously improved to 20/25. Three months later she still
had retractile emboli w ilhin her reLinal a[terioles fH—| lhe
peripheral retinal vessels w ere sheaJhed, and the previous
areas of choroidal infarcls showed pigmentation 1E and JJ. The
emboli arc believer] It) be diulesEerol em boli originating in
Lhe cniolid bulb due to nianipulalion of Lhe hardware! slil h as
Lhe fjuiduwire and caLheLer, and noL Ihe onyx Lised for embo-
lizin^ [he in I ntf ra nial aneurism 'w h ich w ould l>e blacV in
cjcLor).
I ( ! i l u r t n y o l U r. k! ir c n k x j t iLncl Lj r . l-r.snL:<> h li.t i I n ; i . i
occur, bi olhers wilh less ischemic relinal damage the ret­
ina may reLurn to a relatively normal appearance. Some
with persistent low-grade chronic relinal ischemia may
show multiple peripheral retinal hemorrhages (venous
stasis retinopathy) identical to that seen in patients wilh
carotid artery obstruction.Ni' Lj,° Although visuaE recovery
is generally poorr as many as 35% o f palients after central
retinal artery obstruction regain 20/100 or better visual
acuity. Only 1-5% of palients with С RAO will develop
rubeosis and glaucoma, usually within 1-3 mo m bs."
These I alter patients are likely to have significant obstruc­
tion o f the carolid arteiy on the ipsi lateral side. Relatively
few palients with embolic relinal artery obstruction in
one eye develop a similar process in the second eye. Some
authors have found that the life expectancy for palients
wilh relinal arteiy obstruction is reduced.15й 153 whereas
others have noL.1 "' Although there is an increased incidence
of stroke, most palients die o f atherosclerotic heart disease.
It is clinically relevant to classify CHAD into:
]. nonartenelic Q tAO : most ofLen due lo embolism
2. arte re tic С KAO: second ary to giant cell arteritis, almost
all associated with ischemic optic neuropathy
3. transient CRAO: recover? almost complete vision within
a few hours of occluston.
System ic risk factors an d retinal artery o cclu sio n
In 33 patients wilh CRAG seen over 11 years.. 6 4 % [21
patl^iis] showed additional vascular risk factors after the
event; hyperlipidemia was seen in 36%, new diagnosis
or poor control o f hypertension in I t % , 27% had > 50%
carotid stenosis, 13% (6 patients] needed carotid end ar­
te rectomjj and two developed a vascular event, with coro­
nary artery ^ у п ф ш е in one and a stroke in the other. !53
I layreh el at. haw reported in 433 patients (^59 eyes) with
CRAO and branch retinal artery occlusion a significantly
higher prevalence of hypertensionr smoking, diabetes
mellitus, ischemic hearl disease, and cerebrovascular dis­
ease соmpared to a comparable US population. They also
report a 71^6 incidence of carotid plaques in patients with
C RA G and 66% in brancti retinal artery occlusion, abnor­
mal echocardiogram in S.2% of CRAO and 42% of branch
retinal arteiy occlusion.1*' Hence patients who present
with a central or branch retinat arteiy occlusion should be
( reassessed for the associated risk factors and necessary
corrections undertaken.
Atherom atous Retinal Arterial Em bolization
Follow ing U se o f O n yx fo Em bolize Internal
C arotid A neurysm
Onyx is a liquid embolic agent used for occEuding intra­
cranial, renal, and peripheral aneurysms and arterio­
venous malformations (AVMs). In comes in rcady-to-use
vials containing ethylene-vinylalcohol copolymer, d i meth­
yl suIfoxide, and tantalum, '['he polymer is dissolved in
dimethyl sulfoxide, and microni^ed tantalum powder
which is radiopaque, Is added. Concentrations o f 6, 6.5,
and № are variably used. 'I.he higher the concentration,
the more viscous is the agent. After injecting heparin, a
microcatheter is threaded to the nidus of the aneuiysm
and dimelhylsLilfoxide es first iniected to fill the dead space
in the catheter, followed by Lbe selected onyx concentra­
tion. Ilte aneurysm is filled to its neck under fluoroscopic
guidance. This material forms an acrylic cast occJuding the
aneurysm Completely153,154
During the procedure, manipulation of the guidewire/
catheter and other hardware near the carotid bulb can
dislodge a stream o f cholesterol placjues that can ещЬо-
ll)9e the retinal and choroidal vessels. Two such cases are
illustrated in Hgures 6.11 and 6.12 C The overwhelming
feature seems to be the multiple emboli affecting the reti­
nal and/or the choroidal circulation. Since these two cases.
6.12 Fat embolism.
A—H: This 1.‘i-year-old boy brake bis collarbone w h ile pliiy-
ing soccer. He noled а superior visual fluid less lhe nexl
morning. H is visual acu ily was 20/25 and [he superior half
Lit" the macula was perfused via a ciliorelinal artery w hile the
nest of his rotina was o f)aciiiid from occlusion of his сеП1щ1
relinal fertery (A). Autofluoresccnce imaging showed allered
ПиШЁ^бГксс from lhe opacified relina U I . A Iransesopba^eal
счНто гev из It’d a persisLenl foramen ova;e, w hich led to I he
paradoxical fa I tin bolus fnvn the fractured <lavicle.
Branch relinal artery occlusion in protein S deficiency.
C—F: This 40-year-old ivom an of African Am erican anceslry
woke up with a superior field loss in her ri|^hl eye. In addi­
tion to I he compact cutfcular diusen in Ihe fovea b i later­
al lyf there was a rii’hl inferotemporal iiran< h relinal arlejy
occlusion 1C. Angiogmm revealed minimal perfusion of the
involved arteriole and staining of the endothelium at the site
df the thrombosis (D -Я). She was otherwise beallhy anti bad
no known cardiac or vascular disease. There was no family
history of strokes or other vascular diseases. Evaluation of
her Iteart arid carotids yielded no cause for I he occlusion.
A la juratory workup гн-\ч-: ed prole 'i ; t:lr ionty. She was
placed on aspirin therapy and has bad no further episodes.
Her vision remains at 2Й/20 in each eve.
Choroidal vascular emboli during oryit embolization
of internal carotid aneurysm,
G —|: Ttiis 51-year-old wom an underwent onyx em boliia-
Lion of her right superior hyfiophyseal aneuTvsm. A few ho-urs
after the procedure she noticed a ■ ‘'v e il" over her right eye
with fluctuating vision. Her vision was 20/25 on the ri^ht
and 20/20 on Lhe left w ilh a relative afferent pupillary defecl
on lh e righl side. There was faint w hitening of lhe inferior
half ol her rigbl retina {G). N o retinal arteriolar em boli were
seen. Angiogram reveaEed delayed choroidal and retinal fiTl-
irig in the inferior half (3-1-1 Secondary to choroidal emEiolic
infarcl and partial inferotemporal retinal trunk occlusion.
Her vision eventually .improved 1o 20/20 and subjectively the
scotoma faded to becom e almost im perceivable.
IA .h in t H . t c ju r lc f - v <■>! D r. Hjl I w r d S|.i.Lit Jt-. A j A I m j , Y .m n L i^ z l.. L.L w rL'nry; I.,
t h e k t l m . L l A U . i b , J i-iu ru fc rb 21510. 9 7 f U l- 7 [ l 2 l % } . 1 2 0 -0 , f i . i r t l . t i - J . D r.
K.irc;n Icxj: ahd Dr. l-r.mtcj HdLchi.i J
attention is being paid hy the interventional neuroradiolo-
gtsls to minimize manipulation of the guidewire and other
hardware at the carotid root. Other coinplicaliotts include
bleeding at the site of the AVM, bleeding at Lhe percuta­
neous entry site, and anesthetic complications resulting in
oxygen desaturation from dimethyl sulfoxide, though small
and transient most of the time. ' ^
Other Causes of Endogenous
Embolization
Atrial M yxom a
Kmboli from atrial myxomas, benign polypoid tumors
o f endocardial origin arising in the left atrium, should be
suspected in patienLs who have symptoms o f retinal artery
occlusion, usually involving the left eye, and repetitive neu­
rotonic symptoms suggestive of ipsilateral ischemia affect­
ing the distribution of (he middle cerebral artery.1,^,-]C,-,
Signs and symptoms suggesting pulmonary hyperten­
sion and bacterial endocarditis also anay be present.1'"
Ihe tumor is more common in middle-aged Women and
75$| originate in the left atrium. Tumor embolization of
the ciliary arteries (sivelling o f the optic discs and choroi­
dal lesions] has been shown clinically and histopathologi-
c a l l y . Jhe relatively large size and friable naLure of (he
embolus or emboli as compared to a cholesterol or fibrin
platelet embolus is likely the reason for multiple, large-cal-
iber vessels such as the ophthalmic, choroidal, and cerebral
involvement1***45 Embolization o f the ciliary and retinal
vessels with tumor emboli from extracardiac sources has
been observed [E'igure G.IOD-FJ. :, kl' ill<'
Fat Em bolization
following liberation o f neutral fat into the circulation at
[he time o f long-bone fracture or. less often, after injury
Lo fatty tissues, patients may experience sudden cardiopul­
monary and neurologic deterioration. I his usually occurs
after a latent period of 12-3G hours. The pathogenesis is
poorly understood hut apparently is the result of release of
free fatty acids, a toxic vasculitis, platelet fibrin thrombosis,
and obstruction of small vascuEar radicles by macroaggre­
gates of fat. Approximately 5 0 % of patients with fat embo­
lism syndrome may show retinaE abnormalities, including
cotton-wool patches, small blot hemorrhages, and, rarely,
obstruction of major branches o f the central retinal artery
(E-'igure 6.12A and or a fundus picture of Purls chers
retinopathy (see discussion lo follow ].11'’-1''1Young people
presenting with relinal artery occlusion following a frac­
ture should alert the physician for presence of a patent
foramen ovale, the incidence o f which is approximately
29% in the general population {figure 6 .12A and R).
Em bolization C aused by Intravascular
Aggregation o f B lo o d Elem ents
Ihe spontaneous aggregation of thromhofytes, leukocytes
(E’urtscher'sJ, or erythrocytes (sickle-cell; see Eater] may be
the cause of embolic occlusion o f the retinal vasculature in
certain disease sLates.
D issem inated intravascular Coagulopathy
Disseminated intravascular coagulopathy, or patho­
logic aggregation o f thrombocytes, may cause vascular
occlusion in many of the body organs, 'litis occlusion is
much more likely to affect the choroidal arterioles and
6.13 I’urtscher's-like retinopathy.
A—С : Bilateral retinopathy associated with acute pancreatitis
in an alcoholic patient com plaining of bilateral Ions ol" cen ­
tral vision. Arr^io^am :C.'i iJio w s evidence ot loc.il retinal
arteriolar dctlusiqfas in Ihe pftifaVeal пгеа.
D -F: FielinopaLEiy SsSbctated w ilh acufe p,incieal i I i s t?i in
a 3 2 -year-old alcoholic; patient who subsequently becam e
comatose and died. ] t i slopa Ihe lojj ic exam inal ion of I he eye
revealed necrdiis and sweEfirig or the iftrrer IwO-ihlrtJs of the
retina ibl and thrombotic arteriolar occlusion (arrow, F:J.
G - K : l-'tirtscher'H-like retj^opafby in a 2-E-year-old wom an
who noted severe visual loss in both eyes, on awaking
aflur а cesarean SFiction dor^e 1к*саике tnE toxemia of preg­
nancy (C and H ). H e r visual acuily was 2(1/200 bilaterally.
AngiajjiapEiy showed evidence of capillafy nonperfusion cor­
responding with lbe w hile lesions tl and |j . ^ho recovered
20'25 visual acuiJy in Eiolh eyes w ith iгг several monlhs bul
showed evidence of oplic atrophy IK).
L: Furtscher's-Eike retinopathy occurred in both eyes ol this
39-year-oEd wom an with E^pereosiridptHffeL, skin rash, diesl
pain, arthritis, and eosinophilic fasciitis. Visual acuity was
20/40 in both eves.
[ A —Cl.. L t i u r t i - s y o l U r . H . i u J I V , i I(.t i ,: i j .j I , i , I J - K I r n n i К i n c . Lief c L . t l .
L i- K . fro m U lo d i l-I .l I L. B f i u r t a Y <rf 1Эг. A r u n K s ld .j
choriocapjllaris than (he retinal circulation (see Chapter
3). Thromboembolization o f the retinal circulation is
probably responsible for arlerial occlusions that may
affect the brain, hearl. lungs, and kidneys o f patients with
idiopathic persistently elevated blood eosinophilic count
(Churg-Strauss syndrome; see Chapter 11}. ■' ■1 '
Protein S D e ficie n cy
Protein С and protein й are vitamin K-dependent proteins.
Protein S is a cofaclor for protein C. Protein С is activated
lo protein Ca. which inactivates factor Va and Villa, thus
acting as an anticoagulant, and proteolvtically inactivates
the inhibitor to tissue plasminogen activator, thus increas­
ing fibrinolytic activity. Deficiency o f protein С and S can
increase thrombus formation in both venous and arterial
circulation. 'Ihe deficiencies can be congenital (autosoma I-
dominant} or acquired. Homozygous deficiency results in
life-threatening thrombotic disease in the neonatal period,
whereas heterozygous deficiency may result in symptoms
in early adulthood or later. Acquired deficiency occurs due
lo poor hepatic synthesis o f p r o t e i n s . The thrombus
occurs at the siLe o f the occlusion and has been reported in
the central and branch retinal arlery (figure [j.l2C and E3).
cerebral, common carotid, brachiocephalic, and as a cause
of anterior ischemic optic neuropathy.1" " lii0 Recurrent
branch arterial occlusions may occur in some patients,
simulating busac syndrome. 'Ihe absence o f arLerial wall
staining on tluorescein angiography [see figure Ь.21С and
h) helps differentiate Susac sydrome from this. Any artery
or vein can be affected. Olher factors such as pregnancy,
irauma, childbirth, or surgery can sometimes precipitate
thrombosis in these patients. Treatment involves anti­
coagulation with heparin and warfarin.
CJbsritfcdHur Retinal. \rtcrial Dz'prfяйф 463

■
»+
Leukoembolization (Purtscher's and
Purtscher's-Like Retinopathy)
inlravascular aggregation of leukocytes in response to
unusual activation o f complement C5a has been incrimi­
nated as lhe possible cause of retinal arterial embolization
that produces the ophthalmoscopic picture of" Purtscher's
retinopathy. Thfe response occurs after trauma (see Figure
S.06) and in patients with acute pancreatitis (Figure
6 .]3A -F).1 Similar findings have heen reported in
patients with call age n vascular diseases (figure 6.14J!J0,
igjr in patients receiving hemodialysis143; in paLients with
chronic renal failure :'J: or hemolytic-uremic syndrome195;
during plasmapheresis for thrombotic thrombocytopenic
purpura1:J0 and thrombotic thrombocytopenic purpura
per s t 1)7-L?3 Still's disease11-15 and-0Ll [Figure 6.1SA-F), in
normolensive obAtetrie patients after a precipitous deliver}'
induced iviih intravenous oxytocin (Pjt|ocin)(3Ll1 follow­
ing d e liv e r by cesarean section [Figure в. t3C -K j: and in
patients with amniotic fluid embolism,J<" H ELLP syn­
drome {see Figure 3.58J,-20,1 fat ^ n ^ ^ isn u 20^20* cardiac
aneurysm,*" ophthalmic arteiy obstruction,ЛУщ bypereo-
sinophilia syndrome (Figure 6.1SF-E-I), post bone marrow
transplantr cytotoxic drug lherapy->u:' Ju': and reLrobuShar
anesthesia (see E-'igure B .] 2JJ.-': :-jri- '['he frequent asso­
ciation of centraJ nervous system symptoms, in patients
whose ophthalmoscopic picture resembles t’urtscher's reti­
nopathy suggests that leukoembolization may affect the
cerebral vessels as well.
^Lirtscher described multiple, superficial, white retinal
patches, superficial retinal hemorrhages, and papillitis
occurring in five patients with severe head trauma1HC1,l!’"
(see Figure S.06).. lhe pathogenesis of the fundus changes
is not completely understood. lhe white lesions were
attributed Lo lymphatic extravasations secondary to a sud­
den increase in intrathoracic pressure, fat embolism, reflux
shock waves through the venous system, air embolism,-" :
and. laLer, granulocytic aggregation.№
Chronic alcoholics hospitalized for treatment of acute
pancreatitis, with or without signs of central nervous sys­
tem involvement, may suddenly Jose vision in both eyes
secondary to a fundoscopic picture identical to that of
Purtscher's retinopathy (Figure G .H A - F J.1'1''1*41^ '25-1
Shapiro and Jacob studied blood samples of 12 consecu­
tive alcoholic patients admitted for acute pancreatitis and
were able lo demonstrate marked granulocyte aggrega­
tion, reflecting the presence o f activated complement C5a
in eight patients, This lends some support lo the concept
Lhat leukoembolization may he responsible for the fundus
picture.IJ!S
Coin pie menl. platelet, and neutrophil activation and
endothelial dysfunction and inflammation characterize
pre-eclampsia.-'1' these likely exert an effect similar to the
1.14 I’urtscher's-like retinopathy associated with
collagen vascular diseases,
A-F: Ischemic retrtfippathy ir> <
l 2 6-year-old normolensive
black wom an With lupus efytt'jisffiatoiy-s w ho noltd acute
bilateral loss of vision, lethargy, mental in f u s io n , and hal-
lucinatfatis ! A I. Visual acuity was i/200, fcSolh eyes sftmved
a sim ilar appearance. Her bLocid pressure was 120/7H.
Ал^ ioj^Ta phy showed m ultiply branch retinal arteriolar
QccluSlDns and dye leakage from lhe telinal veins Li anq t!:.
1hree years laler visual acuity was 20/100 :n lhe fif^hc eye
and 20/200 in the lelt eye. Note in LJ and t the Optic atro­
phy. Iflffje areas ol retinal vascular nonperlusian, and optic
disc new vesKols larrows, E). After panpholocoa^uJaLion.
Lheru Wttre atrophy and occlusion of lhe disc new vessels iFj.
G-Ki Ischemic retinopathy associated with severe sclero­
derma aлd syslejnic iTyportension in a 54-yea r-ol d wornan
who developed blurred vision in both eyes. Visual acuity was
20/200 in each eye. Note the multiple cottcm-wool patchtes
and incom plete macular Hlar (□). The nonfluoresicenL areas
iH and Jl correspond to cotton-wool patches aлd dye leak­
age (rum the lirrt-order arterioles (arrow, I) and capillaries
adjacent Lo lhe cotLon-wool paLches. The pa lien I developed
pulmonary edema, became Homicomatcfte, and died soon
aflur ihese photographs- were made. Hislopatholo^ic exam i­
nation revealed multiple cyloid bodies (Kj and relinal arterio­
lar occlusions as well at some areas ot fibrinoid necfosis of
choroidal arleries and the chpdocapillaris iarrow, Jl.
mechanism of pancreaLitis causing leukocyte and platelet
aggregation and vascular thrombosis in E^urtscber's-like
retinopathy occurring around childbirth.
Most patients with collagen vascular disease have nor­
mal fundi. Some patients, usually those who have hyper­
tension, may develop retinal or choroidal changes (see pp.
4ЙВ-4!Ю in Chapter 6, and p.. 1ЙЯ in Chapter 3 J.1 A
few patients, particularly those with an exacerbation of
disseminated lupus erythematosus, lupuslike syndrome
associated with autoantibodies lo Sjogren's syndrome A
antigen, derm ato myositis, Still's disease and scleroderma,
may develop acute loss of vision in one or both eyes with
a fundoscopic picture suggesting multifocal embolic reti­
nal arterial occlusions simulating those seen in E’urtscber's
retinopathy (Figures 6.16 and 6.14).li," ':i7~J J '' These
patients often have central nervous system symptoms as
well. The occlusive process may be confined to the poste­
rior pole or may involve extensively the peripheral fundus
(Figures G.16 and бАО А-#)/22—7* 50-236 The reLinal arte­
rioles and arteries may be partly filled with a milky while
material. I hose with involvement o f the periphery may
develop severe relinal neovascular proliferation and vitre­
ous hemorrhage, lhe presence o f anti phospholipid anti­
bodies in patients with systemic lupus erylhematosus also
plays an important role in retinal vascular thrombosis.
(See unusual causes for retinal arteiy and arteriolar throm­
bosis in subsequent sections.)
CJbsritfcdHur Retinal. \rtcrial Dz'prfяйф 465
 The retinal whitening b referred to as a E^urtscher
"Eleckeij and it typically has a clear z o n e between Lis
edge nind an adjacent retinal arteriole (f igure &.ЗЗА,- L).
I'Luorescein angiography in i ll o f Lttese palients who have
an ophthalmoscopic picture simulaLing l:urtscher4 reti­
nopathy is similar. ]l reveals multipEe focal areas of retinal
arteriolar and arterial obstruction, adjacent areas o f capil­
lar.' nonperfusion, and extensive leakage from the vessels
in the nireas o f infarction [E'igures 6. 13 and (t. 14 ). '] his- lat­
ter feature es uncommonly seen in branch arterial occlu­
sion caused by emboli from the heart and great vessels.
IJesolution of lhe white peri papillaiy and macular isch­
emic areas may require several months. Varying degrees
o f narrowing and sheatlning of the retinal arteries, optic
atrophy, and retinai neovascularization may occur [ figure
6.14D-E-). Jn some patients With collagen vascular disease,
evidence o f occlusive arterial disease may be confined Lo
the peripheral fundus and be associated wilh evidence o f
vasculitis and venous si as is.'""
1LislopaLhology o f an eye studied 23 days after onset of
Purlscher's retinopattiy in a patient secondary to pancreaLi­
tis. showed material occluding reLinai acid choroidal arteri­
oles to be positive for fibrin. Коса I areas o f retinal edema,
cysioid degeneration, and loss of inner retinal architecture
wilh a sharp demarcation from an area o f normal retina
was noted. ■'3S
further research is required lo determine the role
o f complement activation and leukocytic aggregation
and embolization in ail of these disorders resembling
Purlscher's reLinopathy. tiy Lhe lime many of these patients
consult the physician, (he level o f complement C5a may
have returned lo nearly normal. Ef elevatEon of comple­
ment proves to be important, then the use o f systemic cor­
ticosteroids has some rationale.'"
Erythrocytic Aggregation
Although the role of erythrocylic aggregation in the patho­
genesis of relinal vascular occlusion is uncertain in diseases
such as diaheles mellitus and bales' disease, there is good
6.15 Purtscher-Eifce retinopathy associated with
thrombotic thrombocytopenic purpura^
Л —E: Ri^hL and left fundus appefifance lin a 2 ? -year-old maie
who presented w ilh acLfLe blurry vision in bolb eyfes for
3 days. His acu i ly was 2CV40 on thy riyhl a п-d 2Q/.100 on lhe
loft. There were several cotton-wool spots and small relinal
infarcls in bolh posterior ЙЫ е* !A and B). A n ^ io ^ am showed
qKTfJjjded relinal в rleriо los and laLe staining of Lhe? vessel
w alls und breakdown. of Lhe btood-^et|rial barrier in Liolh
eyes Hu bad had а rash, fever, Sort I hroaL, jjty^lgia,
thus I pain, shorlness or treaLh, pareslhesia, and weakness
far the past monlh. His sedimenfalion rale was 93 mm/h.
C -read Jvt prolelri 2 J-F mg/d I, w hile counl 27 efipityj, hemo­
globin S ./ j’/dl, .l'lif liver function Lesls were abnormal. He
also had a pleural and pericardial effusion and hepaLo-
splenomegaly. H e was diajjnosed with adull-onsel 51ill's dis­
ease and required plasma exchange, anNrfi^tabolrtes such as
Cytoxan, vincristine, and intravenous immunoglobulin atler
no response to ibuprofen and pultife steroids.
Purtscber-like retinopathy associated with
hype re osi г op li iIia synd rom e,
F- H : This 25-year-old African Am erican paLienl developed
decrease in vision in both eyes associated wiLh cough,
rani:, rind muscle soreness. His w hile counL was elevated
Lo 51 O M l'm m ' w ilh eosinophils.. So t hr retinas- show ed
several relinal fnfSficts and coitort-wiocJ spots simulating
PurEscher's retinopathy LFK The small retinal vessels showed
leakage on an^io(^aphy Bone гид n o w biopsy showed
several eosinophil я with ч&рес1ас1е-ике nuclei" !I—11. Three
days later he developed pleural and peri-cardial effusions,
cardiomyopalhy, uncontrolled hypertension, seizures, right
middle cerebral and bilaleral occipital ir.\ircts.
lA - E , ■:11■.i r li" 1 ^ u l U r. K o L iru u -; h ! i(.ч: A jr H d ® . A l i o , Y j i n r i u i / i . I j w r t a j C B
I ...T h e W ^ tin n i A il: i4 . S m n d c r ^ 2 0 i0 r 9 7 Я - 0 - 7 т 0 - : 3 3 ? 0 - У , p. 194. F - H ,
исзиЛику с>Г Or. iLftuph Млц.шгс.1. 1
evidence Lhat il is important in Lhe case of sickle-cell dis­
ease. 215 increased deformity o f the erythrocytes caused by
hypoxia in the peripheral fundus is probably responsible for
occEuding the small retinal arterioles, capillary nonperfusion,
and reactive proliferation of new vessels into the vitreous
(for further discussion, seep. in CbaplertJ.
Exogenous Embolization
7aIc Retinopathy
Drug users ma\r prepate a suspension for injection by
dissolving crushed tablets, most often methyl p he nidate
(Ritalin), in boiling water. The suspension may be inad­
equately filtered and iniecLed initt&fveiiDUSly, causing show­
ers o f insoluble fillers, principally N ik Lind cornstarch, Lo
embolize the pulmonary vasculature. Larige-caliber collat­
eral vessels are created around areas of occluded pulm o­
nary vasculature after repeated embolization. I'he trapped
particles also produce pulmonary granulomatosis and pul­
monary hypertension; particles that are 7|iin or smaller
can traverse the intact pulmonary bed. lbgether with
larger particles that pass through tEie pulmonary collateral
vessels, they may be deposited as multiple., tiny glisten­
ing, irregularly shaped particles in the retinal vasculature,
particularly in the macular area [E'igure 6.17A, B, and
D) mcjjit patients they produce no symptoms,
in some patients deposits o f this material in the periph­
eral retina may cause areas o f retinal capillary nonperfu­
sion and retinal neovascularization al the function of
perfused and nonperfused retina similar to that in sickle­
cell d i s e a s e . ll' Angiography may show no evidence
o f obstruction or may show small areas o f capillary non­
perfusion, niicroaneurysmal changes, and widening and
irregularities of (he FAZ. Some such patients may have
subnormal acuity. Optic disc neovascularization, vitre­
ous hemorrhage, and Lractioii retinal detachment have
occurred.'11,''!' O nly those patients wi(h Long-term drug
use develop fundoscopic changes. Ihe retinopathy has
been produced experimentally in primates." " ,a,:114 in
patients with a patent foramen ovale, that is prevalent in
29% of population. larger particles cati occlude branch
t. I t Central retinal artery and vein occlusion
associated with throm botic throm bocytopenic
purpura (TTP) and Still's disease-
A - J : Л previously healthy SO-yeai-old W o m a r developed
rash, fever, abdominal pain, and weakness over 1 w eek
and w h s diagnosed as having л dull-on set Still's disease. She
developed encephalopathy and secondary TTP, a tier w hich
she noted bilateral Loss of vision to counling fingers at 6 feet
(2 meters). She had symmetric-appearing exLensive retinal
□ййсШыЕОП and blot hemorrhages consistent w ilh a mm-
bined central retinal artery occFusionVcentral retinal vein
occlusion picture fA and Bl. Anjjiograpliy re v o k 'd w t y fjoor
perfusion of both retinal arteries { t - f f . Her vision continued
lo decline arid dropped to hand motions And light percep­
tion. Intravilreal triamcinolorre (4 mg' did not help her retinal
changes, and sfu1developed neovascularization of the iris on
the right side requiring intravitreat bevacizum ab and panreti-
niiI photocoaguhilion. Й о т eyes uncled with ex Iго те atrophy
erf the retina and sclerosed vessels with no lighl percepUon
vision I (LI—J I.
Ih r u m jc h '/ H . t r lji 4.-1 '' W i [ h p o - m l n - l o r t .)
retinal arteries (Figure 6.17С liiopsy of the pulmo­
nary nodules showed material consistent with laic that
was birefringent under polarizing microscope (figure
6.1 7F and С J. Other foreign materials may occasion­
ally lodge in the reLiual vessels of drug addicts.? ' Itt
those with retinal arteiy occlusion after use o f cocaine,
heroin, and methamphetamine, the mechanism of the
retinal arlery occlusion may be pharmacologic rather than
e m b o l i c . {See Chapter 9}. Veiy tiny talc particles in
a chronic methamphetamine snorter using for more than
15 years has been reported, Ihe mechanism may be from
absorption of the particles imo the nasal mucosal vessels
eventually reaching the lungs and Lbe retina.'' :
Retina,I Em boli From Artificial Cardiac Valves
Clolh particles derived from cloth-covered artificial cardiac
valves may cause loss of central vision secondary lo Fetinal
arterial embolization.11^
Retinal Arterial Em bolization Follow ing
C o rtico stero id S u sp e n sio n In jectio n
Injection of corticosteroid suspensions such as methyl-
prednisolone acetate [tJepoKdedrolJ into the nasal
mucosa, Lips, face, scalp, tonsillar fossa, and orbit, as well
as directly into periocular lesions (chalazion, hemangi­
oma), may pass in a retrograde fash toil into the ophthal­
mic, central retina!, and short ciliary arteries and produce
visual toss caused by infarction of either the retina1''""'1'
or the optic nerve."'4 1 Boih eyes may occasionally
be affected.^0 ihe presence of the drug in both the retinal
and choroidal circulation may be evident over widespread
areas in the fundus (Figures 6.I7E and ] and 6. I 8A-C).
In some cases the patient may regain normal visun:! acu-
ijy ^t.-KM д similar picture has been produced experimen­
tally in dogs.' "
Other causes of exogenous embolization include retro­
bulbar injection of silicone and fat (Figure 6, lR P - lIp ^ -274
surgical enibolizaLion of intracraniaE arteries with poly­
vinyl alcohol,-"' platelet transfusion,"'' 5 fragments of artifi­
cial heart valves and arterial implants, and air,1''4 A picture
suggesting multifocal retinal artery occlusions after local
anesthesia For blepharoptasly was attributed to tissue sub­
stance released into the lacrimal arteiy.-'
6.17 Exogenous embolization of ihe central retinal
arlery.
A and B: Intra-arterial talc em boli in a patient w h o chroni­
cally injected melhylphenidatei (Ritalin) intravenously.
C—G: This 24-year-old wom an was asked to be evaluated for
positive fungal! blood cultures during a hospilal admission for
osteomyelitis. She was visually asymptomatic and found lo
have ,i branch relinal arlery occlusion cm the right and sev­
eral in Ira-arteriolar white pari idea ((! and D). ^he admitted
to having used recreational drugs intravenously Гот several
years. A transesophageal echo revealed a paten I Foramen
ovaie, which alloVied larger talc particles inlo her lefl cintu-
l,i I ion thaL resuJled in lh e ГеМгьа! em boli. A computed lom oj’-
raptiy angiogram ot her с heal revealed a diffuse nodular
pattern isnd focal nodules it. arrowsi. Lung biopsy showed
foreign-body giant-cell reaction lo polartzable material can-
sistunl with laic (F and C ).
H : Retinal arterial embolization after inlmnasal injection
ot melhyJprudnisoJone acetate :n a 24-year-old w om an
who com plained Ql "cham pagnc bubbles,* numbness of
tfie upper lip. and transient blindness of the ipsilalera! eve.
Visual acuity returned Lo 2СУ20 30 minuloH ar'lor injection.
1 and J: Retinal Mrrows.i and widespread choroirlal arterio­
lar em bolization in a 35-year-old paLient who experienced
a positive scotoma, orbital pain, diplopia, and visuaF loss
immediately after injection erf methyl prednisolone acetate
into the ipsi lateral nasal turbinates. Visual acuity initially was
20/£10 bul returned lo 20/20. tin e day later most of lhe reLi-
nal emEioli w ere no lonj^er present. K a le lhe inlrachoroidal
rm boli were less apparenL f|).
IA лпгЕ 11. lu u M c ^ ' оГ U r. М 4тк I. iJ.iily : f.-Lj, frurn Ijr.tn l'jl,: Я л ]./ .
H - l, lrr>m H-vcrf-." ''J 1979, Am rricj-n M e d k .il .''.iMJi-Mtion. All rij^ib
fbOitrViJ. I
■

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-■ iZ> R i
Obi iterative Retinal Arterial Diseases
A rterioscfero sis an d A th e ro sclercsis
focal narrowing iiaf the major arteries supplying the ret­
ina caused by arteriosclerosis and atherosclerosis With
Lbrum basis may cause lhe typical picture of Cl? AO or, less
oftenr branch retinal artery occlusion, It is probable that
this mechanism for occlusion occurs less commonly than
eipbolizattbn, particularly in cases of branch artery occlu­
sion. Systemic atherosclerosis may affect the ophthalmic
artery and the central retinal artery up lo the level of (be
lamina cribrosa, but rarely does it affect tbe more anterior
portions of the central retinal artery. The reason for this is
uncertain hut may be related Lo (he absence of (he inter­
nal clastic lamina in the retinal arteries, which have a com­
plete muscular coat out as faF as the equator.J ' b Although
primary atherosclerosis of the retinal arterial tree is rare.,
the formation of secondary: often uonobstnictive athero­
matous plaques at focal sites of retinal arterial wall dam­
age may develop in association with a variety of disorders,
including arterial maeroaneuiysms, usually in patients
with hypertension (see p. 4У4 in Chapter 6), toxoplasmo­
sis retinitis [see Kyrieleis plaques, figure 10.22K-U), bilat­
eral idiopaLhic recurrent branch relinal artery occlusion
(see p. 474 in Chapter 6), acute retinal necrosis caused by
herpes zoster (see Chapter 10) large-cell lymphoma (see
figure ] 3.J? 1 It), and chronic uveitis.1'''
Unusual Causes of Retinal Artery and
Arteriolar Thrombosis
Occlusion of the central retinal artery, presumably caused
by thrombosis, may occur occasionally in association with
systemic diseases including essential (hrombot^themia/
LbromboLic thrombocytopenic bomocystin-
UFia, mild hypeFhomocysLeinemia in heterozygotes,
anliphospho lipid antibody svndrome (Snedden's
syndrome},:^ '- - ^ '- ^ p ro te in S deficiency,1™ 1™ (ligure
6.]frC-lr) protein С d e fic ie n c y ,a n d Lyme disease.'"
Multifocal arteriolar occlusions associated with bone
marrow transplantation may simulate [^urtscbers reti-
nopathy."381'-'100 El Is uncertain whether these arteriolar
occlusions occur primarily as a complication of irradiation
or some other mechanism such as leukoembolization. The
administration of fibrinolytic agents, such as tranexamic
acid, to reduce lhe chances of bleeding may occasionally
6.18 Exogenous embolization of the central retinal
artery.
Л —E: A 1.1-year-old ^irl received 1 ml uf methv! prednisone
ateLaLe lo a Bfbgrejeftfli hemangioma a1 lhe Lip o f her гкгее.
Уbe lost i onstiousness 1 2 0 seconds afLer die injecLion.
On fw p ffin g сопнсюиагтеу;; she cnmplaLhBd of visual loss in
bulb eyes. to no li^hl perc up-l i o n . Both reflirias showed srw-
eral intTa-arLunal em bulit material and areas ol relinal and
ctioiiiidal wbiLeninj* IA and t?'. t’aracenlesis ol lhe anterior
chamber Ln bcub eyes improved vision to oounl finders bilat­
eral Iy. The emboli had broken down 4Й hours I ale" and lhe
vision had improved Lo 20/200 (t ). Her vision gradually
improved t-q 2 0 /ft0 tin lhe ri^bl and 20/3(1 on the left over
10 days w hen Ibe relinal o p a f i fit л Li и n had failed and all lhe
emboii had disappeared (L'J and Li and evenHjallv Iо 20/30
on I be rijjhl and 20/20 on Lhe left by 1 year.
F-lr Ischem ic TelinopaHiv and crtoraidopalby caused by
embulizaLion o f silicone injected mlo Ibe lid. The pa Lien I
experienced sudden loss of vision immediately atler Lhe
injeclion. Note lhe multiple blfjtc hy relinal hemorrhages
Allgiajfrapby reveal ml mul Li focal filling delects n lhe cho­
roid Hi and focal retinal arteriolar leakage .
I.A—t , (.uurlLvx i il' Or. VI iii Liujjl.,1 ;iiy J Ljr. АггикЕ Li Lrjl-,1.'
promote spontaneous thrombosis and branch relinal
arteryr occlusion.^'1
Arteritis an d A rtenolitis
A variety of inflammatoty disorders, some infectious and
some of unknown etiology- may cause acute obstruction
of either or both the ophthalmic and relinal arterial circula­
tion,. e.g., cat-scratch disease, (see p. 812 in Chapter 10]. her­
pes zoster [see pp. Й9Й-ОД0}. mucormycosis (see p. 844 in
Chapter 10}f toxoplasmosis (see pp. 848-852 in Chapter
10),J|J- gjant cell arteritis-4 (see figure 6.23С-l), hypereosino-
phi lie syndrome.1 ■ ' eosinophilic fasciiLis [figure 6.131. and
6.15F-E1). Churg-Strauss syndrome (allergic angiitis and
granulomatosis. Figure 11.51 ),L- Kawasaki disease,2-1
’* idio­
pathic multifocal retinitis (see p. 86 in Chapter 11J. and acute
multiple sclerosis Although the retinal occlusive dis­
ease seen in these patients* as well as in patients with collagen
vascular disease, has been attributed by some authors to arte­
ritis- the arterial obstruction may be caused by other mecha­
nisms. including hypertensive arteriolar narrowing, immune
complex vascular damage, thromboembolization or leuko­
cytic aggregation, and embolization (see discussion under
leukoembolization, p. 464 in Chapter
Idiopathic Recurrent Branch Retinal
Arterial Occlusion (Susac Syndrome)
Apparently heal thy individuals w ay develop, in one or
both eyes, visual Loss caused by recurrent episodes of
muLliple branch retinal arterial and arteriolar occlusions
Lbat often spare centraE vision (I'igures & 19^6.21
3Mrrtue scotomata jnay be accompanied by pholopsia,
typically characterized as irregular shimmering, geomet­
ric iines or shapes of light just preceding a new scotoma
and confined to the area destined lo become scolomatous
(^ 5 % )Г vestibuloauditory symptoms (50%); other tran­
sient focal neurologic symptoms, often affecting the face
and upper extremities (3 0 % ) [Figure 6.J9A-F); and a his­
tory of migraine [40%). defined as recurrent episodes of
scintillating scotoma (with or without headache) or severe
one-sided headache with nausea.103 Memory and cogni­
tion disturbances with confusion and bizarre behavior
with mood ;ind personality changes may accompany, pre­
cede.. or antecede the other symptoms. I he disease affects
20-40-year-olds of both sexes wilh a slight preponderance
in females.
It is considered to he an autoimmune endotheliopa-
tby involving the arterioles of the brain, eye, and cochlea
and is also referred to as relinocochleocerebral vascu-
Lopalhy. The focal relinal arterial obstruction is umisso-
ciated with visible emboli, may occur in the midportion
of an artery and al arterial bifurcations, and es frequently
associated wilh focal periarterial whitening and fluores­
cein angiographic evidence of segmental arterial stain­
ing near ihe sile of ihe obstruction and elsewhere in ihe
fundus [E'igure Sheathing and multiple
periarterial yellow-ivhile plaques often develop along (he
obstructed arterial segmenl and may remain permanently
[figure в. 19G, H, Kr and L). Hgan et al. named these Gass
plaques [Figure 6.19 EC].-Mk-JOiS in some cases only a ghost
remnant of the completely occluded arterial segmenl
remains (figure 6.2] A and Ci). These patients are subjecL
Lo recurrent relinal artery occlusive events that, in some
cases, may extend over a period of 10 years or more.№L
Retinal, optic disc, and iris neovascularization may
develop in 25% of eyes and requires phoLocoagulation or
6,19 Idiopathic,. bilateral, recurrent, branch relinal
arterial occlusion (Susac syndrome),
Л —F : rhis 26-уеаг-оЫ wom an noted (innitus and mu Hi pie
negative and scintillating scotoma La in the left eve associ-
aled with muhiple b iaiK ti relinal arteriolar occlusions (A).
A nil ioij гл pbv re".f ill'd m .illiple knjal ii-is :э1 rolin.il ч1<г\
and лтГагтЗаг slainin^ and occlusion IB and C"). Sbie sub­
sequently developed similar occlusions in (he ri ц Ы eyie
(arrows, D-F: and had multiple oilier e p is tle s ol branch
arterial occlusion d № r a 1-yaar period. Medic.al evaluation
was ne^alive. W h en Iasi seen !>years after the onsul of symp­
toms, her visual acuity was 20/20 in both eyes,
G —|: Tti is 4 Q - y еат- o l d m a n h a d m u lt ip le b ra n c h retinal a rtery
d c t Iunions in h o l h eves o v e r a 3 - у в а г p e r io d . D e s p it e m u lLf-
ple e xte n s iv e m e d ic a l e v a lu a tio n s , n o c a u s e w a s f o u n d . N o t e
Lhe j^hostinjj a n d sheath in jj 0f the relinal arteries, periarterial
p la q u e s , a n d fo c a l area o f retinal n e o v a s c u l a r iz a t io n (a rro w s ,
I a n d | . W h e n iast SEwn 13 years after И ге onse t o f h y m p l o m s ,
visual acuiLy w a s 20?2(J.
К iin-ri L: frei&arierial piaque associated w ilh bilateral, recur­
rent branch relinal artery occlusions ot unknow n ( .^ute in a
!>1-year-old man. Ih e plaques becam e less promin-ent over a
4 -year period farrowsl.
in some cases vitrectomy (Figure 6.191 and joe
These patients are frequently SLLbjecled (o multiple exten­
sive unrewarding in ed tea I evaluations. Standard screening
lests for blood dyscrasia, dysproleinemias, and coagulop­
athies, including those for .mliphospbolipid antibodies
and naluraE anticoagulant deficient stales; imaging tests of
lhe carotid arteries, heart, and brain: and screening lests
(excluding magnetic resonance imaging: M R I) for systemic
vasculitis are Lypically negative. Johnson el al. found mul­
tiple lesions compatible with focal brain infarcts in one
of three patients sLudied with M R lftl Jbe angiographic
and ophthalmoscopic findings suggest that focal retinal
arteritis and arteriolitis, perhaps caused by precipitation
of immune complexes along the arterial wall, are respon­
sible for the occlusions. Ihe occasional association with
serologic evidence of cytomegalic infection and protein 5
and protein С deficiency disease in these patients may be
coincidental. 3?a
 Most patients wilh idiopathic recurrent branch retinal
arteiy occlusion are part of the triad of the syndrome of
multiple branch retinal arterial occlusions, hearing toss...
and encephalopathy (Susac sydrome). The triad some­
times is not apparent for a few years and die diagnosis
may be delayed.' ' Ihe encephalopathy usually develops
subacutely and oflen includes psychiatric features, person­
ality change, and bizarre and paranoid behavior.m '['he
hearing loss is usually bilateral, asymmetricr and is oflen
associated with tinnitus, vertigo, and ataxia. Low and
medium frequencies are affected, localizing the lesion
to the apical portion of the cochlea. MKJ of the inner ear
fails to show microin fa rets in the inner ear. MRI typically
shows numerous infarcts in white and gray malter. more
often in the periventricular region and the central pari
of the corpus callosum, and may show ieptomeningeal
i n v o l v e m e n t . r|"he lesions in the corpus callosum are
smallr multifocal г and enhance in the early stages of the
diseases (Figure 6.2] Jj. 'Ihey are responsible for the behav­
ioral manifestations, 'lhe lesions are hyperintetise on T2
fluid-attenuated inversion recovery [FlA lR ), Diffuse tensor
imaging may be able to detect white-m alter abnormali­
ties in the early phase of the disease. 1Ъе clinical findings
and MR] changes are often attributed to M S'"'4-111 or acute
disseminated encephalomyelitis. Jhe key differentiating
features on M.RI are central corpus callosum involvement
in Susacrs but peripheral in Mb and acute disseminated
encephalomyelitis, Iepto meningeal involvement is lim ­
ited to busac, and basal ganglial lesions are seen more
often in Susac and are rare in MS,31' The cerebrospinal
fluid examination usually reveals minimal pleocytosis.
Jhe clinical course in these palients with encephalopathy,
hearing toss, and multiple branch retinal arteiy- occlusion
can be self-limited, ranging from 1 lo 2 yearsr with a good
prognosis.11- Elowever, in some patients, the disorder may
be progressive and resuU in severe visual loss and death
(E’igurefr.llC-L).
Pathogenesis of the disease is poorly understood.
Lndothelial deposition of C4d demonstration histo­
logically (Magro CMj unpublished data), serum anti
endothelial antibodies at a titre of ]:960, and indirect
immunofluorescence demonstration of IgC, subclass
&,20 Idiopathic recurrent branch retinal artery
occlusion associated w i(h cerebrovascular
fnvoEvemenl.
A—F: In February "19Б6 this 4B-year-old wom an with л long
history of migraine headaches experienced a sudden onsel
o f a paracentral scotoma in [he righl eye associaled with a
small branch retinal arlery occlusion. In Lhe asymptom­
atic tel low eye she had evidence of а branch retinal arlery
obstruclion Iarrow, A and multiple focal areas of relinal
arterial w all permeability changes (C and D ). Several days
after initial examination she developed dizziness and diffi­
culty 5wn I lowing and In I к ini’. The diagnosis “ brainstem
migraine." O ver the next 2 years she experienced m ul­
tiple branch retinal arterial occlusions (Er February 34J56:
F„ Augu-bt lF)3f)l. Extensive m edical and neurologic investi­
g a tio n including assay For prole in (I. prole in 5, and lupus
anticoagulant w ere norm ;iI. O ve r tHfe nexL 3 years she b id
no furl her ocular or neurologic iwmptoms. l-ler visual acuity
when last seen correcLcd lo 20/1 5 bilaterally.
G-L: In D ecem ber 19B4 this 71-year-old man presented
w ilh a J-month history of progressive loss ol vision m the
left eye and a 5-day :iistory of headaches and loss ol" vision
in lhe right eye. His pasl medical history was unremark­
able excepL for well-LonLroiied systemic hypertension. His
visual acuity was 20/25 right eye and hand movements lefl
eye. There were multiple branch retinal arteriolar o cclu ­
sions.. extensive atheromatous retinal arterial changes, and
scattered relinal hemorrhages in both eyes (G—IJ. The lefl
optic disc was pale. Fluorescein angiography revealed e v i­
dence of extensive retinal artery and arteriolar occEusion (J>.
The patient was hospil aliped. and medical and neurologic
evaluations, including temporal artery biopsy, cerebral arte­
riograms, and computerized scans of the brain, were nega­
tive. In J.inuary ] (>G5 he developed n ew paracentral branch
relinal artery occlusions in the right eye (K). In April 1УЁ5
he developed bilateral vitreous hemorrhage and prolifera-
live reLinopalhy -L'i. His family noled IhaL he had a change in
personality. In June 1 985 he developed signs of a right-sided
strode, and progressive mental deleriuralion; he died aMer
cardiac arresi io September
antibodies1*1 suggest the disorder lo be autoimmune in
nalure. Eilevaled levels of factor VUE and von Willebrand
factor antigen may be the result of endothelial damage.
Response to steroids and immunosuppressives also lends
strength to the autoimmune hypothesis.
 A specific treatment is yet to he con firmed since lhe
disease etLopathogenesis is not completely understood.
Treatment has evolved over die years and currently is a
combination of systemic corticosteroids, immunosup­
pressives,. and immuno modulating drugs. For an acute
severe presentation, intravenous immunogitihulin (1VIG,
2 g/kg divided over five doses) every other day along with
a high dose of systemic steroids Li begun. IV LG Ls given
every month far the first year or so and then maintained
at 2-monthly intervals indefinite]у lilJ the disease shows
no flareups over a few years. SysLemic steroid is main­
tained at a moderate dose for (he first few months then
at a low dose for a few years. Mycophenolate mofelil
has been substituted as a steroid-sparing agent in some
patients. Cyclophosphamide has also been used as a long-
Lerm immunosuppressant in place oFlVEG. Most recently
riLuximab, a monoclonal antibody is being tried.1..... 1 by 2 weeks: over the course of several previous and fur­
Some patients have a self-limiting disease that quietens
in 1-2 years and do not require long-term maintenance
therapy.
Young patients with branch retinal artery occlusion
associated with idiopathic multifocal retinitis and neu­
roretin ilis {cat-scratch disease) may simulate idiopathic
recurrent branch retinal artery occlusion [see Chapter 10,
Figure 10.04),
X-Ray Irradiation
Exposure of ihe retina to X-ray irradiation may cause
retinal arteriolar narrowing cotton-wooi patches, cap­
illary telangiectasia, and retina! arterial occlusion (see
pp. 554-5 5G) * 5-’17
6.2 E 5 usac's s y n d ro m e .
A—H i This 25-year-old w om an presented with diplopia and
ataxia in 1999. She was diagnosed with mu I Li pie sclerosis
when magnetic resonance imaging ItvLKI> shewed while-
maLter changes, and was lreated w ilh intravenous methyl
prednisolone and pelted cm mLerferon-1-alpha. Two years
Eater she developed a visual fit'Id defect in her right eye and
M a tin g loss, when she? received in Iravenous melhyl pred­
nisolone. Her visual loss improved bul hearing remained
impaired. Л year laler she noted a new field loss m her lefl
eye w hen she was evaluated aL VandefhilL and diagnosed
и-s EiaVinjj SusaCs syndrome. She had a Ires hi supefoiempo-
ral branch relinal arleiy occlusion on the IdL with relinal
whiLening and evidence of old occiusion on lhe гiцЬI A and
E3). Angiogram showed typical finding of iiusac syndrome
wiLh fusiform staining of the involved vessel w all (CJ and
other uninvolved vessels IE; and prevfbLisw occluded ves­
sels on Ihe right ■1 . The relinal whjitening faded sOmewhal
ther episodes her o p lk nerves became pale 1G and H}- ih e
had patchy lield loss, lhough her cenlral vision remained a I
20/25 in each eye. 5Eie was Healed w ith ini ravenous im m u­
noglobulin (IVEti) and systemic sLeroids and maintained on
monLhlv 1VIC injeclions. She conlinues Lo remain slable.
I- L: This .VI-year-old w om an in 1^)15, soon after lhe Ejinh of
her second child, was evaluated liy her psychiaLrisL for per­
sonality changes and diagnosed with anxieLy and depression.
O ver the nest 10 years she developed episodic hearing loss,
and visual field loss I ha I was atLri billed to лти1Ир]е sclero­
sis." In Lhe m eanwhile her cognition was impaired and she
had E>ecome a "slow Lhinker." She was Lreated w ilh ini ra­
venous melhyl [HBdriisdpAe and sLarled tin inlerferon-l -
alpha. In 2QQ7 she presented lo Vanderbilt with bilateral
visual field defects attributable Lo fresh branch -retinal arleiy
occlusions 111. ih e was diagnosed as h^tvin^ Susac's syn­
drome and started on IV IC , oral steroids, and methotrexate.
An МКГ of her brain showed several callosal I . periventricu­
lar, cortical, cerebellar, and ponUne hyper intense lesions on
T 2 fluid-atlenuated inversion recovery (FL A I Kl imaging. .She
developed a superolemjioral arterv occlusion in Ihu righl eye
a le w monlhs later w hen she self-decreased her oral predni­
sone iK). Note the narrowing at ihe sile of previous o cclu ­
sion in lhe inPerotomporal arteriole La now ). An angiogram
s h o w ™ Ihe typical fusiform slain ing of the affecLed and
unavTecbed vessel walls IL, arrow heads). HEie also shows e v i­
dence of past occlusions in llte inferonasal arteriole. ilie has
remained withoul further relinal occlusions o w r lhe next S
years and is on m aintenance tVICJ and a very low dose of
prc^dnisone.
|J, iM iurlL'i v jjI U r . iiijd h .L r.im .'i W iw .ite.-
®

©
Retinal Arterial Obstruction Caused bv
Spasm
Some degree of reflex spasm probably plays a role in reti­
nal arterial obstruction from many causes. Lhe ocular
fundi of patients yrtth amaurosis fugax have been observed
numerous times during лп allack ' Lhe characteristic
picture described is pallor of the optic di.se And marked
narrowing of the retinal arteries. With restore Li on of circu­
lation. vision promptly returns, tn some cases this spasm
may be associated with recognizable causes, such as ocu­
lar migrainer collagen vascular disease, sickle-cell disease
(see Figure G.6QA-H), inhalation of cocaine [t-'igure 9.13)
and amphetamines, and administration of proprano-
jDj ]t рГС?ЬаЫе that some cases of isch­
emic infarction resulting from relinal arteiy occlusion are
caused by prolonged spasm of the central retinal arteiy.
in lhe review by Brown and associates of a series of 27
patients under the age of 30 years who had retinal artery
occlusion, lhe only associated finding Was migraine head­
aches.; ' 4(1 Woller and burchfield^-1 reported a L2-year his­
tory of recurrent episodes of lotal vision loss in one eye
associated with a cherry-red spot and complete recovery of
vision in a 20-year-old in an with ocular migraine. It is of
interest (hat the photographs in their case show narrowing
of the retinal veins rather than the arteries. This same phe­
nomenon was noted in another patient by l?r. Mark Daily
(E'igure 6.221-1 and I).
Retinal Migraine
IJelinaE migraine is a rare cause of transienL monocular
visual loss, firel described by Galezowski in 1BS2, It is
usually characterized by episodes of partial or complete
reversible monocular visual loss ipsilateral to the head­
ache and lasting less than an hour. Sometimes it can result
in irreversible visual l o s s . ' [ ' h e 2004 International
Headache Society criLerla for the diagnosis of retinal
migraine are as follows1' 1:
Л. At least two attacks fulfilling criteria В and С
Hully reversible monocular positive and/or negative
visual phenomena confirmed by examination during лп
attack or by Lhe patient's drawing of a monocular field
defect during an attack
C. ]■Lead ache fulfilling criteria - migraine without aura
begins during the visual symptoms or follows them
within 60 minutes
l.>. Normal ophthalmological examinations between
attacks
h. Not attributed to another disorder.
]"he condition is more common in young women in their
second and third decades. Lhe field defect may not always
be from the retina; the optic nerve or lhe choroid may be
the site of spasm, hence "monocular migraine” may be a
belter term.j:iS'13e When examined during an episode these
b.2l Episodic vasospastic central retinal artery
occlusion,
A - G : This young black wom an w ilh lupus pry! bem alosus
fiп[I sicklo-Le! f^emaglofcrin С diabase e^rerEenced epinodes
ut" blindness, each lasting 1-3 minutes, in the right eye sev­
eral times daily. During an episode I fie retinal arteries were
narrowed ‘.A). Angiography revealed Lolal oEretrucLion nr" lhe
ccnlral retinal artery and slow filling ol bodi n'tinal veins anri
arteries via optic disc collateral vessels (EJP 12 seconds: C.
27 seconds; LJ, -10 second ь; L, Й5 seconds after injection ol
Lhe dye). As vision retUrtted Iо norm ill, dil.iMon ol lhe reti­
nal arLerius and veins occurred ■Fj and angiography revealed
normal relinal perfusion [Cjk Hut Hi^ns and svmpLoms Tailed
Iо Respond la blood Iran sin sions but did so aJLty hyslemic
corli a s te ro id treatment.
H and I: Focal conslriction of relinal veins i.fcj occurring dur­
ing an episode of ucuLir migraine. Compare H w ilh asymp-
lom alic slale in E.
1Л. L. I-. ind С (runi jh.i'.v M a I !l1'; hi and I, r:uurk'iy jjf l>r. Muгк I
D.Lily.J
patients may have an alTerenl pupillary defect, ronslricLed
retinal arterioles, pallor of the optic disc, retinal whiten­
ing. and occasionally relinal venous 0Dnst№^0bnb32r,--lJ7,J2e
The documentation of a visual field defect that completely
reverses in association wilh headache on lhe side of the
visual Loss is necessary lo make the diagnosis.. Treatment
wilh propranolol can prevent future episodes and should
be begun in a confirmed case.01 These patients should
be differentiated from patients with recurrenL branch reti­
nal artery occlusion of Susac syndromerJ2fl amaurosis
fugax from carolid embolic disease, retinal arteiy occlu­
sions from collagen vascular disease such as lupus and
anlipbospholipid syndrome, protein С and S deficiency
and in older patients from giant cell arleriLis, polyarteritis
nodosa, and eosinophilic vasculitis.
Retinal Arterial Obstruction Caused by
Diseases of Surrounding Structures
Acute closure of the retinal arterial circulation may be
caused by diseases primarily affecting the surrounding
tissues, including inflammatory diseases such as reti­
nal toxoplasmosis (figure Ю.22Л-С), neuroretiiuLis/ w
Bartonella associated muUifocal retinitis and neumreti-
nitis1^ [see Hgure 1 0 .0 4 and orbital cellulitis; external
pressure on the ophthalmic, central retinal, and cilioreti-
nal arteries such as in orbital hemorrhage.14 cavernous
sinus thrombosis,1*-' inlereheaLh peri optic hemorrhage,: u
papilledema-1 J u ischemic optic neuropathy optic disc
d ru s e n ,c e n tra l retinal vein occEusion,^:' and neo-
plaslic diseases of the orbit, optic nerve, and retina-^7;
carcinomatosis of lhe meninges of the brain and optic
nerve1™; and surgical manipulation such as retrobulbar
procedures,
 Branch. retina] or cilioretinal artery occlusion may
accompany central relina] vein obstruction in Lhe same
eye.' " " J in лоте eases both may be the result of primary
disease effecting the optic nerve head. ]n other patients,
particularly those with cilioretinal artery obstruction,
the central retinal vein obstruction may he the cause of
decreased perfusion within the cilioretinal artery that nor­
mally has a lower perfusion pressure than the central reti­
nal artery,11 J
Retinal Arterial Hypoperfusion Caused
by Systemic Hypotension and Ocular
Hypertension
Reduction of retinal blood tloxv in patients during systemic
hypotensive episodes rarely produces evidence of retinal
ischemia unless il occurs in patients with pre-existing dis­
ease causing reduced retinal flow.34? Marked elevation of
intraocuEar pressure may cause symptomatic optic nerve
or retinal ischemia, particularly when it occurs in patients
with other diseases, such as stckle-cell disease, (iompression
of the eye and orbital tissues during general anesthesia in
Lhe face-down position may occlude the ciliary and central
retinal arterial blood supply lo the e y e . ( S e e Rgure
3.54К and I..} This can also cause posterior ischemic optic
neuropathy.
Retinal Arterial Hypoperfusion Caused
by Carotid and Ophthalmic Artery
Obstruction
Reduction of retinal arterial blood fiow may be caused by
obstruction oJ" either or both the ipsilatEral carotid and
ophthalmic arteries.l04,i4fr Whereas this obstruction is
usually caused by slow progressive narrowing associated
wilh atheromatous disease, it may have a variety of other
causes, including giant-cel I arteritis/’' spontaneous dissec­
tion/ fibromuscular dysplasia [t-'MD),"- surgical com­
plication,1 '''Takayasu's disease.1^ '1"1' and cavernous sinus
thrombosis.'^2 Rapid obstruction such as may occur in cra­
nial arLeritis (figure 6.23CM.), mucormycosis, or herpes
rosier causes acute visual toss and ischemic retinal infarc­
tion.'" 1 Lhis is often accompanied by signs of ciliary' artery
obstruction, pallor of the optic disc, and hypolony (Figure
6.23J and ]n a few palients multi­
focal areas of ischemia simulating Purlscher's retinopathy
may occur [E'igurt- 6.16Н].:Й [f obstruction of the major
arteries occurs more slowly from atheromalous disease or
chronic inflammation of the large arteries {Takayasu's dis­
ease), reduction in blood flow to the eye may or may not
be sufficient to cause visual coin plaints (figure 6.23Л-С).
A variety of fundus pictures may occur: ( 1 ) minimal or no
ophthalmoscopic changes in patients complaining of tran­
sient loss of vision in one eye [amaurosis f u g a x j ( 2)
few widely scattered blot and dot retinal hemorrhages and
k.23 Ca r(itid and oph Ih aim ic arle гу о bstruct ion.
A—С : b?loLc:hy peripheral retinal hemorrhages and relinal
capillary charges larrows, A j in a 57-year-uld man w ith a
4-month history o f frequenl 3-10-minuie episodes o f "tog­
ging" of vision o f Ihe right eye. There was no oilier history
of lransionl ischemic Attacks. H e Itad xanthelasma for
yea re. Visual acuity was 20/20. O phlhalm odynam om elry
wan 25/20 in lhe right eye and 1 1(V40 in lh e left eye.
Алдк 1£тар 1ту showed increased relinal iM fllla B a n lime,
microaneurysms* and di la Li on of relinal capillaries [О- Гlie
loft Cundus was normal.
D -F: Loss of peripheral vision, hypolony, and a .iftO" serous
delnchm-unl of the Ciliary body and choroid developed in a
72-year-oEd aphakic mar 3 weeks after medical evaluation
qeStectBa ipsi Ja LeraI carotid artery obiilrljfcthari. tliJiochoroidal
ddnchmcnl nasal ly oxtended almost lo the optic disc ■15 and
E, arrows). Note lhe round retinal hemorrhages that were
preh-enl throughout Iho m idpenpiiery of lhe eye. there whs
iip ii lli. ilrn i^iv: l-iin mi м.' I гi: i " . ':i:' i-I.- f I n.i-ki'd roducliun in
Lhe ophthalmic arlery pressure.
G - l: This elderly wom an noted the sudden loss o f vision in
lhe lefl eye. Her vision and the [undus of the ri^h! eye were
normal 'C j. Visual aeility ]n lhe leil eye was 2Q/20U. Note
in the lefl fundus- !ht' palchy dense whilem n^ of lhe inner
juxta papillary retina (H.i and lhe diffuse whitening of the
relina superiorly. On lhe following day she jwvfllie with no
light porcepLion in lh e riglu eye. Ehe ri^hl oplic disc d ip p e d
swelling and pallor It) typical ol ischem ic optic neuropathy
associated w ilh gianl-cell arteritis, which was demonstrated
histopathoiogicaEly on temporal artery biopsy. Intensive cor­
ticosteroid therapy was given. Ten months Eater she remained
blind in the right eye and retained 20/70 in the left eye.
I and K: Unilateral blindness caused by ophthaFmic artery
occlusion in an elderly palitinl w ilh era n ini I ajterilih. Note the
aafttJt of :he optic disc and harrowing of lhe retinal vessels
caused by previous obstruction of t i nculation in the cenUal
relinal artery; also noLe the segmental atrophy of the retinal
pigment epi I helium caused by obstruction o f lhe short ciliary
aiterial circulation ; and Kj.
L: Hislopathology o f Ihe temporal artery in a patient w ilh
craniiil arlerilis. N ote severe narrowing of iht! vessel lumen
by jifiinuloniiilous arlerilis.
mild dilation o f the retinal veins (venous stasis retinopa­
thy}.. usually in palients with minimal visual complaints
(Kigure (3) dilation of the retinal arte­
rial tree, dilation o f the relina veins, and cotton-wool isch­
emic patches {Figure 6.23H); (4] retinal capillary changes^
incltiding microaneurysms, cysloid macular edema (Ш Е ] ,
and angiographic evidence of areas of capillary- nonper­
fusion that may be confined Lo the area along the hori­
zontal raphe (figure 6.23A-C)-!'"t-,(' :, (5) larger areas of
peripheral capillary’ non perfusion, retinal neovasculariza­
tion, and hemorrhage; ( 6) any degree of branch or cen­
tral relinal vein or arterial obstruction [Figure 6.2313); (7)
ischemic optic neuropathy (Figure 6.231); and [tfj any of
the above associated with panuveilis, neovascular glau­
coma. and a rapidly progressing cataract [ischemic ocular
syndrome).21*'5' ^
 Dt. Gass has seen one aphakic palitnl with carotid
лrt-ery obstruction develop loss of vision caused by acute
exudative detachment of the choroid and ciliлг>г body
(E'igure 6.23Q-F), 4'he detachment resolved rapidly after
carotid endarlerectomy. Ih e ophthalmologist faced with
any patient who has these ocular signs or symptoms
should (bqulie abouL other signs or symptoms of tran­
sient ischemic attacks and should look for other evidence
of ipsiLiteral carotid artery obstruction- such as reduction
of carotid artery pulsation, a bruit over the carotid artery
and orbit, and ease of col [apse of the ipsilatera] central ret­
inal artery with finger pressure on the eye compared With
that of the contralateral eye. fluorescein angiography in all
such cases should show a late appearance lime of the dye
in the central retinal artery and choroid and a prolonged
retinal circulation time. In some cases a dramatic improve­
ment in the fundus changes may occur after carotid
endartereclomy.
Takayasu Retinopathy
Mildlo 'L'akayasu in 190S described the ocular manifesta­
tions of this condition as 'peculiar changes in the central
retinal vessels and wreaLb of arertiovenous communica­
tion” around the optic disc., 'lhe retinal changes include
d data Lion of the retinal arteries and veins with beading
(l':gure 6.24[ and |). microaneurysms at the capillary level
and along the arterioles (very typical: ftgtciE 6.24A- К E-L),
vascular occlusion, large zones of nonperfusion, arterio
venous shunts, relinal and optic disc neovascularization
(bigure 6.241 and L), and, occasionally, vitreous hem­
orrhages. Ilte arm lo retina lime and Lhe arteriovenous
transit times are p r o l o n g e d . E ]oor blood flow to the
eye is lhe basis of the ocular findings and is seen in those
patients wilh involvement of the common carotid arter­
ies (ligu.re b.J!4G and E1). The left side is more commonly
Involved than the right. Since the intra vascular hydrostatic
pressure is low. these patients have very few retinal hemor­
rhages, and minimal leakage from the new vessels (ligure
6.14 E.) and microaneurysms. 4'he poor endothelial oxy­
genation causes a break in the blood-retinal barrier and
mild fluorescein leakage, bul much less intensely than
other conditions such as diabetic retinopathy. Intraocular
pressure is low due to poor perfusion of the ciliary body;
eventually rubeosis irides (but rarely neovascular glau­
coma) and cataract develop. I radion relinal detachment
and phthisis bulbi have been seen very occasionally 'iTiose
patients wilh renal artery stenosis without involvement of
the carotids show features of hypertensive retinopathy in
the form of arteriolar narrowing, retinal hemorrhages, and
arteriovenous crossing changes.
Takayasu arteritis, also known as "aorta arteritis" and
"pulseless disease," is a form of chronic granulomatous
panarteritis With possible autoimmune origin lhal affects
the aorta and its branches. The coronary and pulmonary
arteries can sometimes be involved. W hy it is more com­
mon in Asia, Mexico, and other tropical countries is not
fc.24 Takayasu retinopathy.
A —H: A 2 S-year-old tasL Indian wom an had a 6 -man Ih his­
tory of d jminiiticm or vision in both eyes accom panied by
giddiness, which recovered on lowering her head. H e r visual
acuily Was 2 0 / 2 0 0 in each eye and inlraocular pressure 6
and 7m m Hg respectively, lhene went1 no iris new vessels and
pupils w ere sFujyjish. MultipEe microaneurysms were seen in
Eioth eyes, w hich went! significantly mere common anterior
ifi the equator, and several on the larger arterioles (arrows
A and Й). There was remarkable delay in dye appearance in
Ejoth the choroidal and retinal circulation. Several m icroan­
eurysms as well as dilated capillary bed tilled on angiogra­
phy. The late frames showed diffuse vessel w all staining of
ail retinal vessels "C lo F-l. Her physical exam was sifjnificiinl
far absent radial and brachial pulses. She underwent com ­
puted tomography: angiogram of the arch of the aorta and
its branches was su ^ estive o f type 4 1'akaysu arteritis involv­
ing lhe ascending arch and descending aorla, left pulm o­
nary aTterv. bilateral com m on carol id artery, brachiocephalic
trunk, E>ilateral subclavian and axillary arteries (C and Ы:.
She was treated w ilh oral steroids.
l- L: This W-year-old Indian female was seen for opisodjc
headache!; and Irequenl blackouts. Her vision at initial eval­
uation was ^О.'ЗО both eyes, bul subsequently declined over
a year to-couni finders in both eyes. llolii eyes showed sev­
eral microaneurysms, marry o f them on Lhe arterioJes arrow.,
dilated and sausage-shaped veins ■:I and l.i. There we-re no ret­
inal hemorrhages due to slow flow in the vessels. The Teft eye
also had a large K V t J (ll. An an^io^ram flicks up the numer­
ous microaneurysms (K), and late frames show breakdown in
the blood-relinal barrier dae to endoLhelial hypoxia. Note
lhe N V D does not leak early due Lo Ihe verv slow blood ffow
throughout the relina it . Her blood pressure was unnccord-
able in lhe Upper limbs and measured 1 Ь 0 / А О тт Н ц in bolEi
low er imbs. Her carol id, radial, brachialis, and suEjcI avian
pulses were absent bilaterally, but Lhe femora I, popfiteal,
posterior lib-idl, and dorsalis fred is w ere present. O it an aor-
Logram lhe rrj^hL suliclavian artery was absonL, only slumps
of Lhe lofL com m on caroLid anrl subclavian w ere seen, and
Lhere w ere ricEi collaterals between Lbe intercosta Is anti asil-
Eary vessels. She had type 2 Takayasu arteritis.
[A-L, Ldtarieiy ul l>r. AmnrJ Uupl.i: 1-1, (.uurlL'w 1 1 Г l>r. Vi stun ii f.i ip l ; ;ind
Mi. Antod Ou|jt,i.i
fully understood. A link lo poststreptococcus auloimjuune
change or to tuberculosis has been p o s t u -::M
Intimal proliferation and fibrosis of the media wilh scar­
ring, thrombus formatioLi, and eventual stenosis of the
affected artery occur.
A female preponderence of up to У: I is seen in Asia,
and affects young adults who present wilh clinical features
based on the vessels invob'ed. '['hose with involvement
of the branches of the aortic arch present with amaurosis
fugax, dizziness, and syncope. Renal artery stenosis leads
lo hypertension and its manifestations.
Takayasu arteritis is classified based on vessel involv-
mcnt using radiological imaging into six groups1" 1:
■ lype I: branches of aortic arch
■ Type I Ел: ascending aorta, aorlic arch, and ils branches
■ lype lib: descending thoracic aorta with or withoul
ascending aorta, arch, and its branches
* lyp e J U: -descending thoracic aorta and abdominal aorta
* type JV: abdominal aorta only
* Type Щ aortic arch, descending Lboracic aorta, and
abdominal aorta.
Пнтару depends on Lbe stage of the disease, [f the patienL
is seen Early in Lbe course of arteritis without signifi­
cant occEusion, systemic steroids and immunosuppres­
sives alone are indicated. О nee occlusion or significant
slenosis occurs, angioplasty and bypass grafts are needed
in addition to the immunosuppressives. -
Medical management of hypertension, nephrectomy,
and autolransplanialion of the kidney may be necessary.
Antituberculous drugs In those patients with highly posi­
tive Mantoux. lest is indicated.i?-
Fibromuscular Dysplasia
KMU is a nonatheromatous, noninflammatory vascu-
Ear disorder thal commonly affects the renal and internal
carotid arteries, it is known to cause choroidal hypoperfu­
sion central relinal arteiy.. and ciliorelinal arteiy occlusion.,
though extremely гаШу.3*0-341 JJetinal hypoperfusion,
and its various manifestations, leading to retinal neo-
vascularEzalion and traction retinal detachment, simi-
Ear to Takayasu retinopathy, has been described in one
patient.u " A fatal stroke and multiple retinal hemorrhages
have been seen in an l i -month-old infant.-'14 When a
young patient without cardiovascular risk factors presents
wilh a С KAO, one should rule out lliese patients
may have recurrent strokes, transient ischemic attacks,
syncope, headache, tinnitus, and cranial nerve palsies.'141
Unlike atherosclerosis lhal affects lhe proximal or origin
of the caroid artery, 1MD affects the middle or distal part
and has a typical appearance on carotid Doppler/angio­
gram with the "pulled screw'7 configuration, focal tubular
narrowing, or localized outpouching of the artery. 'i|,J Ibese
configurations occur specifically in the three types of IM D
( ! ) pulled screw or multiple constrictions in the medial
type; [2 ) focal tubular narrowing in the intimal type;
and (3J outpouching in Lhe adventitial type Aneurysms
and Involvement of olher medium-sized arteries can also
occur. Genetic risk factors are being investigated, as the
disease is known to occur in first-degree relatives.
Retinal Hypoperfusion Caused by
Cardiac Anomalies
Young patients with congenital cyanotic heart dis­
ease commonly develop some dilation and tortuos­
ity of the major relinal vessels often associated with
polycylhemia.^-^Frank central retinaE vein occlusion,
atypical mbeosis i rid is can be seen rarely*3S:>3^ Patients
Hypertensive retinopathy.
A - C : This- ^J -year-o Id womflti had a visual acu ily of 2!O/fl0
secondary L-cj sevejffi raj$fcrtensEve retinopal by. NoLe the
m acular sLar, coLLon-wnol B.alcheJ} and Eiemonhages. Early
arleriovenous-slage angiogram f- s h e w e d N a jr o w iJn ii t>f lb e
first- And second-order arterioles jarrq w i) suppm ng Lhe
Macula IK) and patchy Gaining of Lhe retina corresponding lo
areas of dilated L’api Hades (Cj. Note Lhe absence ot fluores­
ces n starninu; in lht? m acu la.
D -F: Foveal hemorrhage (D l ел used by hypertensive micro-
vascular changes evident in the angiogram i L ■. NoLe Lht?
w hile puncLale fle a ® tin the surface ol" Lhe oval sufjerficial
relinal blood a rd Lhe F&fgef атеа гл" subreiinal blond. Seve*al
imonLhs laLtTJ lbe bltHjd Lien red lLi and lhe; visual acurty
returned to norm ill.
G - l: Ischemic oplic neuropathy and branch retinal arte­
rial ocdusron in a patient With яел/йгб chronic1 hvperlensit>n.
NoLe lhe sharp derma real it jn Jinc M m iw s, ( Ji separating Lhe
ischemic. relinal whitenjng from ^hc nonischemic peripheral
nelina in the areas of distribution of the obstructed artery. The
peripheral retina retained ils Ira п-нрагел су Ье^ аш е ot previ­
ously established col 3aLera I arl trial channel я :arrows; ■ lhal
became murn apparenl several mombs later in H and I.
I —L Purtscher's-lilce retinopathy in Lhis .^fl-year-old man
caused by central retinal artery obstruction in a patient With
hypertension. He noted blurred central vision in the [eft
eye lhal progressed over a ptiritJtl of 24 hours to include
lhe ел Li re visual field. His visual acuiLy was 1/200. Note
Lhe severe reLinal whitening in- lhe papillom acular bun­
dle .re.i <:ntl rclin.il '.viiikning in Lhe m.u .il-г .ire.i.
A n l;iot^ia phv revealed delay i n perfu s юл o f I he rel inal с i re u-
Ia Lion. Echography revealed dislen^ion nr" lhe leM oplic nerve
sheaLh with fluid. -Carotid artery studies w ere negative. His
serum 'riglyceride was '>44.
with pulmonaiy hypertension and a reversed bidirectional
shunt through an intracardiac defect (Eisen monger's syn­
drome] may develop retina! micro vascular changes simi­
lar lo that in patients with carotid artery obstruction. ""
Paradoxical embolus due to a right-Lo-left shunt can cause
retinal artery occlusion. ***
Retinaf Arterial Hypoperfusion Caused
by Occlusion of Retinal Venous Outflow
Lf severe and rapid obstruction of the central venous out­
flow occurs before collateral channels of venous out­
flow begin to function, severe ischemic whitening of the
retina, in addition lo widespread retinal tiemorrhages,
occurs, producing Lhe ophthalmoscopic picture of com­
bined central retina] arterial and venous ppdusion,331^ 9
Obstruction of the central retinal vein may cause selective
obstruction of a ciIioretinal artery because of relatively loxv
perfusion pressure of the cilioretinai arteries ).l3fiiUlim-59L
RETINAL ARTERIOLAR
OBSTRUCTION CAUSED BY
SYSTEMIC HYPERTENSION AND
COLLAGEN VASCULAR DISEASE
Ihrough auto regulation, reLinal arteries respond to an
elevalion in .systemic blood pressure by constriction. Mosl
patients, however, with chronic mild Lo moderate degrees of
systemic hypertension have no Visual complaints ant! mini­
mal or no fundoscopic changes [focal and diffuse narrow­
ing of Lhe relinal arteries, an increase in the arterial reflex*
and arteriovenous crossing changes), which are caused by
thickening of the smalt arterial and arteriolar walls (arterio­
lar sclerosis). '!J:: Kocal narrowing of the major retinal arterial
branches is the single most reliable early sign of systemic
hypertension Fluorescein angiography usually shows no
evidence of microvascular changes in patients with mild lo
moderate hyperl^bsion,22t,39J Retinal and op Lie nerve
arteriolar sclerosis is of palhogenetic importance in lhe fol­
lowing causes of central vision loss in hypertensive patients:
( ] } branch retinal vein occlusion (see p. 556); [ 2] arterial
macroaneurysm formation (see p. 4 9 4 and (3) ischemic
optic neuropathy (see pp. 12ti4-1 S}.
Patients wilh more severe chronic or wilh accelerated
malignant hypertension may develop marked arterial acid
arteriolar constriction and evidence of focal vascular wall
damage that is mosl severe al the origins of first- and sec­
ond-order retina] arterioles tn the posterior fundus [Figures
6.2 5A-С and 6.26El and |^395-1|] Leakage of blood ele­
ments into the arteriolar wail causes narrowing or cloture
of arterioles and focat ischemic whitening of the retina
(cotton-wool spoLs) in the vicinity of the optic disc and the
major retinal vascular arcades posteriorly [E:igure 6.25A).
Part of the intense whitening in collon-wool spots is caused
by stasis of amplasmic Tow wilh in the nerve fiber layer in
Lhe area of relinal ischemia.^” '11'1 Microaneurysmal forma-
Lion. irregular telangiectasis, occlusion, and increased per­
meability and remodeling of ihe retinal capillaries within
and around these ischemic areas are best, seen with fluores­
cein angiography (Figure 6.25B, C, and
Jhese changes may persist after disappearance of lhe cot-
ton-wool patch. Ehey are responsible for varying amounts
of intraretinal serous exudation, yellowisb exudation, and
retina] hemorrhages that are usually confined to the periph­
eral macular area and are associated with varying degrees of
Loss of centra] aaiily [Eigure 6.25A and 6.27). I'ocal depres­
sion of Lhe inner relinal surface may be evident biomicro-
scopically afler disappearance of a cotton-wool patch.-" 1
In the presence of marked ischemic arteriolar and capillary
permeability changes in the relina and optic nerve head,
a macular star and swelling of lhe oplic nerve head may
develop (Figures 6.25A and (j, and 6.26E.}). borne loss of
central vision may accompany these changes and prob­
ably is primarily related lo ischemic damage to the nerve
fibers within lhe optic nerve rather than alterations in the
macula, which is protected by lhe rich pattern of collaleral
6.26 Hypertensive retinopathy, optic neuropathy, and
choroidopathy,
A - C : Unilateral ischemic optic neu*opalhy and m acular
slar c-ii Li:--L'( I bv s e vH t, previously undiaj^ntfted hyperten­
sion in а 56-year-uld wom an com plaining o f headacEres and
blurred vision in lhe njjht eye. Note the irregular attenuation
□I the relinal arteries (arruw, A). Visual acuity was. 20/40.
^ j E e j r a p h y revealed shaming of lhe o plic disc and no sLain-
in^ in Ihe macula.
D - F: Biliileral sld3ale exudative m a ty lopathyr seious mac u-
lar delachm enl, collon-wool ischemic pattbes, and mulli fo­
cal grav-while ischemic relinal pigment epithelium iRt’ii
lesions (arrows, E and F) in this palient w ilh severe hyper­
tension. Focal areas of fluorescein staining in the temporal
m acular area (arrows, are a I lhe level ol' Ihe b!l-3E.
: -L: Hem orrhagic delat limenl o f lhe inlernal limiUnjj mem­
brane (G J in n -t'M'ear-old w om an with severe Erv'perleni-ion.
The hemorrhage was caused by rLiplure of a small superfi­
cial relfnaE capillary. Note Ihe vertical wrinkles i.lop arrow:
of the inlernai ItmitifW membrane and E)ltx>d pooled inte­
riorly around lh e bleeding sile ibollom arnowi. ihere was
wrinkling of the inner retinal surface caused by an epi retina I
membrane in the Eeft eye fHJ. The visual acuity was 20/25.
NoLe the fine relinal folds secondary lo Iranslutenl epirelinal
membrane over lhe superior and nasal part of the macula.
AngJograpfry in Ihe lefl eye :Ij showed early leakage of dye
from dilated capillaries and a chain of micnoaneur^Hms sur­
rounding a focal zone o f capillary nonperfusron (lefl arrowf,
and oEislruclion of lhe frrsl-order arlurioles Irijjhl a rro w .
This palient died soon afler these photographs w ere laken.
H istopatEiologic findings of the eye illustrated in С showed
bliWjjd and p iцдтепI-laden macrophages benealh lhe in!ernal
limiting membrane larrrjw, J Histopathologic examination
of the relina in lhe Tcgion of the left arrow ir> I revealed e v i­
dence ol a cytoid body (K). A fihrocellular opirelmaE mem­
brane (arrow, L was presenl inferonasal lo )he macula.
frurn U.LJi.'' . ' 1н>Ьй Altierkrin \1l i I;.,:I Abi::-: j.ilrtjn A-lii^his
r ts e lV ts l.)
circulation. Swelling of the disc caused by ischemic papil-
lopathy ntay occasionally precipitate branch relinal arterial
occlusion that, because of we]l-deve]oped collaleral arte­
rial circulation, may show an unusual distribution of reli-
nal whilening (Figure 6.25Ci-E). Some patients with severe
hypertension may have mild blurring of vision, a macular
star, and swelling of the optic nerve head (grade IV hyper­
tensive retinopathy; E'igure 6.27A-F) and only minimal exu­
dative and ischemic changes in lhe retina otherwise (Figure
6.26A-C). Ihese palients, who often have headaches and
undiagnosed malignant hypertension, may be mistakenly
diagnosed as having neurorelinttis. Ijebefs stellale maculop-
aLhy, or papilledema. Other patients, particularly children,
may experience marked visual loss caused by severe isch­
emic papillopathy and massive extension of intraretinal and
subnetinal exudation inlo lhe macular area.5!h,Jia Patients
wilh moderate lo severe chronic essential hypertension usu­
ally do not show ophthalmoscopic of fluorescein angio­
graphic evidence of choroidal ischemia.lQft [See Chapter
3, p. IS 2.) Patients with rapid acceleration of malignant
hypertension are mosl likely to develop choroidal vascular
complications [I'igures 6.27 and 6.28).
 Angiographic changes in the microvasculature., even
in the presence оГ grade EV hypertensive retinopathy. aFe
primarily outside the central macular area. Following
medical control of malignant hypertension, angk)graphic
evidence of permanent remodeling of the relinal capillary
bed (microaneurysms, capillary telangiectasis, small areas
of capillary non perfusion, and permeability alterations)
is most prominent in Lbe imaapapiLlary area and along
the course of the major relinal vessels posteriorly [Figures
6.25D-Ev and 6.261i and l).JU Hemorrhagic detachments
of the internal limiting membrane of the retina in the
macula may arise from these permanent microvascular
alterations (figures 6.25EJ-K and 6.26t;-J}_ '['here is prob­
ably an increased incidence of epirelinal membrane for­
mation in the macular region in patients who have severe
hyperLen&ive vascular changes [E'igure 6.26] ■ ! and L). Ehese
patients are susceptible to all of the со mpl tea lions of arte­
riolar sclerosis mentioned previously in patients with less
severe hyperlens ion.
During exacerbation of collage]! vascular diseases
patients may develop cotton-'wool patches that may occur
in the absence of significant elevation of systemic blood
pressure.l^ M “ SJ '^ 4DJ i|Chi‘ll5-4]b Although in some cases
Lhe cause of the arteriolar obstruction ts identical lo that
produced by severe hypertension, in other cases it may
occur by a different mechanism such as thrombosis from
a hypercoagulable state associated with a lupus pnUcoaguk
lartt1®1"2"' J H (see discussion of leukocytic aggregation
6.27 Hypertensive retinopathy optic neuropathy, and
choroidopathy,
A - D : л 19 -year-oid African Атетзсап №>гтЦп with hivtcny
ot sYst^mic lupus erythematosus chronic renal failu re and
hypertension presented with vision ol" 20/1 foD on the rig^il
and counting fin^erh on I ho l3oth eves had tw u llen optic
discs, with exudation of fluid and lipid along with retinal
hemorrhages and cotton-w oo I spots secondary to hyjNJften-
sive retinopaLhy and optic neuropathy IA and B). She was
hospitalized and lhe E>]oud pressure was brought under ton-
Iroj. Two week? idler her vision had improved to 2{J/S0 iind
20/300; Ihu optic disc edema had improved significantly,
more on the right than Ih e Eefl ( t and Dj. She returned to the
hospital Fur uncontrolled byperlension a few weeks later bul
ocular exam w-ns not sought.
Hypertensive retinopathy and choroidopathy.
E and F: Hypertensive reLinopalby, charuidopalhy, and esu-
daiFve retinal detachment in (his patienL show ing peripapil­
lary nerve fiber hemorrhages, cotton-wool spots, choroidal
infarcts lElschnfg's spots\f and inferior dependent subretinal
fluid in liolh eyes :E and arr-t^ws).
lA —O, U U t a | f иГ дЛт Vl^I I Urn I- M ju Ilt A .mil H. AJkj, Vaiip'dzti,
L.iwrtricuP.. Ihu T5l-I-i i-il Allafc S,iun<Jcpi ?C11C), 07^-70:0-i.i20-4,
|]. л а в л
and embolization, pp. 464, 565 and figures 6.13r 6.14
and 6.62). Ehese patients also may show evidence of
occlusive vascular disease affecting the choroidal vascula­
ture (see pp. 40. 84. 464).
 All of the retinalr choroidal, and tjptic nerve head
c h a n ts set’]i in Ьшдалз with accelerated hypertension]
have been reproduced in the rhesus monkey using л modi­
fied Ooldblatt procedure. W9-,*MWl?-'U J Hayteh and oth­
ers described .1 peculiar focal intra retina I perEarteriolar
transudate that frequently develops during the first few
weeks after the onset of experimentally induced malignant
hypertension.1*1" Unlike cotton-wool spots, these pinhead­
sized, dull-white, deep retinal lesions that are associated
with punctate fori of fluorescein leaks are specific for
malignant hypertension (l-'igure 6.28). Ihey probnibly rep­
resent focal ischemic damage to the Kl’L.
6 .2 Й H y p e r te n s iv e c h o r o id o p a th y w ith e x u d a tiv e
re tin a l d e t a c h m e n t
Л -L: This ahorl-bta Lured m^iLch had receivLid a kidney [r;in*i-
planL for erd-stage гелл! d beast 1 rt-sli 11i nj^ Irrjm л posterior
urelhral valve. He had developed secondary hyperpara­
thyroidism and renal osteodystrophy due lo nonLom pliance
With phosphate binders. Vision was counting finders at 1-2
fool (30-b0t:mf in both eyes. Both retina:- had small '.el-
low distinct-appearing spots all over the posterior pole w ith
overflying m acular detachments and large inferior delach-
ments with shiflin^ flu.d -A-Dj. A ti d iog'raii hy showed 1n i Ii л I
hypefl'luorescence of Lhe lesions that leaxed dye late, w hich
pooled in lhe subretinal space |E and Fj. OplicaE coherence
tomography confirmed loLLitated StJibretinal fibrosis in boll:
maCulas :G anti Hi. He was hospitalized, his Ы Ьй р pres­
sure was broughl under control from I 9CV1 .Iftm m Hjj, and
.117r_>i:m .;nd hypok.ik'nii.'i wi.v< irf-ih-i. f V.e wf-i'k l.ih" I■
-i-
vision improved Lo 2Q/5i) on lh e ri^lil and 20/2 00 о л the I el I
and 2.5 weeks later lo 20/25 and 20/30. The exudative reti­
nal dutachmenLs m soked, leaving residual chronic Llschnijj’s
spots w ilh distint.1 ed^es !I—L 1.
[O lurCrsy ol Ur. M.irk J ILn[Гil■I.:f..1
A C Q U IR E D R ET IN A L A R T ER IA L
M ACRO AN EURYSM S
Parents who develop acquired retinal arterial macro­
aneurysms are usually in their sixth to seventh decade of
Eife when they seek treatment because of visual loss caused
by exudation or bleeding from lhe aneurysm. Typically a
solitary round or fusiform aneuiysm arises on one of lhe
four major branch retinal arteries., usually within the (hird-
order branches (Figures 6.29 and б.ЗО).'*- л~**° 1"he aneu-
г\гки1 occasionally develops on a cilioretinal artery or on
the opLir nerve bead.'4' it occurs more frequently in
WoK^fcdJ4M,*<5j44ti ]"he superotemporal arLery Is most ran-
mo nly affected. ' I he alieu rys m о flen ocru rs at the si le о f a n
arterial bifurcation or an arteriovenous crossing. In some
cases it may puEsale.4^ 1'1'1' Pulsation is not a reliable indi­
cator for high risk of hemorrhage."1' The author has seen
one pulsating macroaneurysm spontaneously disappear.
The right eye is affected more commonly than the lefl
eye. Aneurysms may be present in both eyes in approxi­
mately 10% of cases. A total of 50-75% of palients with
acquired arterial macroaneuiysms have a history of sys­
temic hypertension and/or ophthalmoscopic evidence of
retinal arteriolar sclerosis. Some assocIatlon wilh systemic
.sarcoidosis has been noted, though Lhe relationship Is not
understood. Visual loss is most frequently caused by leak­
age of proteinaceous and lipid-rich exudates, often along
wilh some blood from the aneurysm, into lhe surro иtiding
retina. L'his leakage produces an area of clrclnate retinopa­
thy that includes the macular area (Figures 6.2')A, F. and
C. and 6.30D). ierous detachments of the macula (Figure
6.30D) and bleeding beneath the retina, the internal lim ­
iting membrane,. posLerior hyaloid and into the vitreous
are olher causes of vision loss (figures fi.29J. 6.30J i and
К and 6.31).’"^ Bleeding may occasionally be precipi­
tated by a Valsalva maneuver." Jn cases associated with
6.29 Acquired retinal arlery macroanetirysm.
A—F: C irri nate maculopaLhy caused by retinal arterial
тасгстпеитуягп in a 4^-year-(jld Etypi^rtensjVe wom an w ilh
a visual acuily of 20/40. Note the local atheromatous cuff
larrow. Л) jusl proximal hi :!icj iirtnun am. there w±s minimal
evid en ce of obstruction of arterial flow either by the aneu­
rysm lletfL anruw, Ef or by Lhe atheromatous cuff (right arrow}.
The laLe angidjgKrfl ^C'i showed m inimal slaining ot (he roL-
ina suirounding lhe aneurysm larrow'i. Argon laser troalmenl
(D) was applied Lo the aneurysm and sunounding relina.
' ive months laler 11;■ visual -acuily whs 20/20. N o le Ihe alh-
enoma lesion in lhe small retinal arlery (arrow I is s:i 11 visible.
Several years lal^r the had developed a new macroanrtirysm
find pxudaliun nasally in Ihe same eye il.. NoLp lhe aLher-
om-a (arnjw, Fl in the arlerial w all dislal lo the aneurysm.
G - l: Vitreous hemorrhage and uncinate maculopaEhy caused
by an accpined rulinal arleriaf macroaneuR'sm J arrow, C ).
Angiogr^phv (H i confirmed the presence of" the aneurysm
(arrtnv). Sixteen months la!er.. fallow iFgj parLial sfionlanenus
resolulion of vilroous blood and relinal exud)dE .I ■ , visual
acLi i I v was 2 0 /.10 . Note thflt Ihere was no ionger any caudate
in lhe foVealar. area iarrow..
3—L: Serous and hemorrhagic detachment of the inlernal lim­
iting membrane of Ihe retina was caused by a m aooaneu-
rysm larrows) in Lhfs patient. NoLe the blood in the inferior
pa К ol Lhe detachment as w ell as another boat-shaded area
и! subhyaloid blood interiorly. Angiography (K and LJ dem­
onstrated dye leaking from the aneurysm.
bleeding, Lhe blood is often presenl in front of and pos­
terior to the retina and may partly or totally obscure the
aneurysm from view [Figure 6.30H). Full-thickness macu­
lar holes can occur as a complication. High pressure under
the internal limiting membrane resulting in foveolar
necrosis or secondary vitreofoveal traction as a sequela to
the hematoma mav plav a role iin lhe palhgenesis of the
Ь о Й Й »^ Ч
Ac^uiijE^. f& fina! A rit'h n i Mdcncrtrtefrr^snsS *|95
 Subnet ina I neovascularization, though rare, has been
reported.4*1 Occasionally multiple aneurysms occur along
the same sit^ y (figure 6.3CJGJ or elsewhere in the eye,
Approximately iO^'o of patients have one or more focal
yellow arterial w ill plaques either proximal to or, less
often, distal to the aneurysm (Figure &.2УЛ and l:). These
lesions, which often incompletely surround the blood col­
umn and do not interfere with blood flow, are probably
Localized deposits of serum fat (atberomata) occurring
at the site of defects in the arterial wall. These represent
potential sites for future development of an aneurysm.
Prevkhidy these atheromata have been misinterpreted as
embtil^*29r4i3,il4S,<1,3 ratients with these plaques show no
clinical evidence to suggest embolic disease, Lvidence of
branch arterial occlusion distal to the aneurysm may be
present {figure &.Э015 and H).
branch retinal vein occlusions occasionally may occur
within the same or opposite eye..'N:' "l"he arterial macro-
aneuiysm may be within the area of the branch vein
obstruction or remote to it. This association of these two
disorders is not unexpected since hypertension is a risk fac­
tor for the development of both. Muorescein angjography
may fail to demonstrate the aneurysm when it is partly
obscured by blood or exudate [L:igure 6.301). Angiography
may show evidence of complete (figure 6.30h.), partial
(Figure 6.2LJB), or no obstruction of the artery at the site
of the aneurysm,.'1-11, in some cases a few microvascular
abnormalities may be present in the vicinity o f'the aneu­
rysm. These include widening of the periarterial capil-
Eary-free /one around the aneuiysm. capillary dilation.,
small areas of capillary non perfusion, microaneurysms-
6.30 Acquired retinal arterial macroaneurysm.
A-< : МасГггапеИгузЦ (arrow, A I causing subrelinaf and
relink I hemorrha^y,. as wtill as m acular delach merit. S o le
the Evidefttfi of Hlainiitu anftio^rap-hi-LJ^iLly (cirrow, B). Visual
лсиМу w.is 1 j/ 2 0 0 . E Eeven monlhs laler Ihene wan йЬогдапе-
ous то?ыо ILrlfcm of the {.■Kudate and blood (C l The HineUryifrt
u rro w ) dppauryd shrunken and starred. Vis ил I acuity was
20/30.
D and E: iuTous m acular delachmuni ismaH arrow*: luuslmJ
by an acquired macnoaneurysrn llar^e arnowj. NoLe obstruc­
tion of ihu dye flow ,il Iho she of the a n eu ftim u rro w r Ej.
F and G : Acquisition cl л m acroanuuryim ■irif’hl arrow.
C| ^nd c iгечплLc axudalion in a 7-year-old hypertensive
worn л n. H o le lbe small arteriali лпиигунт llcft anow, C j л I
the site of a previous retinal hemorrhage ;H l. CL, was made
5 years л tier F.
H artd 3: Н е то г гЬ л ц к retinal duU-chmenl and viLneoub hem-
urrltrige Iha I simulated а mulanoma w ifi caused Eiy rupture
of an acquired rdtlnal лПигЫ тл его а п и и гуьт ''arrtiws, H
and I). NoLe [he failure oJ the aneurysm, w hich was Locally
obscured by blood, [o oirelruct the flow trf litioruscein. The
subretina I blood cleared 5ропЕлпеои&1уг and visual acuity
was 2 0 /.Ю 2 years later.
J: Sobnefifial hemorrhage caused by arterial та сго л п еегун т,
snd cystoid т л с и 1аг edema caused by old тг"ого1о т р о г л 1
branch reLinaf vein obsl rue lion in л hytipriensii» patienl.
К and L, iubm lim il and stininterni (Uniting membrane hom-
оггНлуе with fluid level caused by arlEtrial т а с г о н т 'и г у а т
farrows'!.
and intra-arterial collateral vessels. Leakage of fluorescein
occurs primarily from the site of the aneurysm and to a
much lesser degree from the microvascular abnormalities
immediately surrounding Lhe aneurysm.
 I I islo pathological Iу macroaneurysms show evidence
оГ a linear break in the artery wall surrounded by a thick
Laminated layer of fibrin platelet clot and varying amounts
of blood, exudate, lipid-laden macrophages, hemosid­
erin, and tibroglial reaction (figure 6.3] С -E:)."137, Hl'kM'
Similar miliary aneurysms may occur in the central ner­
vous system on vessels thaL are 100-300|im. 'Lhese
are more commonly found in hypertensive individuals
than in normal individuals. Although lhe pathogenesis
of Lhese aneurysms in the eye and central nervous system
is uncertain, they probably occur at sites of focal arterial
wall developmental and aging defeels, which particularly
in a patient with hypertension are more likely Lo decom­
pensate (figure 6.2УА] Lhe presence of focal atheromala
eilher adfacent lo or in other parts of the retinal arterial
Lree is evidence of the presence of other focal defects in lhe
arterial wall, which in some cases may lead to future devel­
opment of additional aneurysms. Eiecause of the associa­
tion of hypertension. Lhese patients probably are at higher
than normal risk for stroke and cardiovascular d is e a s e .'
tvidence suggests that, following a period of exudation
and hemorrhage, the defect in Lhe arterial Wall may close
spontaneously (hrough a process of thrombosis and scle­
rosis (figures 6.29G-I and 6.30A and In some cases
the retinal artery may be almost completely restored to its
normal caliber. Additional aneurysms may arise elsewhere
(figures b.lOY and 6..30H and C). lhe visual prognosis is
excellent in most cases. Patients With chronic yellowish
exudation in the macula and ihose with evidence of bleed­
ing into the subfovea] area are the most likely to lose some
vision permanently l.arge hemorrhagic detachments of
Lhe retina in these patients are often mistaken for sub reti­
nal hematomas caused by age-related macula; degenera­
tion, and occasionally for a choroidal melanoma [figures
6.3(J] I and I and 6.31A-C). ,Q,<‘35 The eccentric location
of the hematoma centered beneath a major retinal artery is
an important clue lo the correct diagnosis when the aneu­
rysm is obscured by inlraretinal or p re retinal blood. When
associated with cirrinale yellowish exudation- a macro­
aneurysm may be misdiagnosed as retinal telangiectasis,
branch retinal vein occlusion, diabetes, and irradiation
retinopathy. 'I'here is usually no difficulty in differentiat­
ing patients with acquired arterial macroaneurysms from
older patients with congenital retinal, telangiectasis, 'lhese
latter patients, most of whom are males, usually have
multiple arterial aneurysms, larger areas of capillary drop­
out, and more extensive telangiectatic changes involving
both the capillaries and the veins (see p. 514]. A peculiar
6 .? !E H rsto p a th o lo g y o f re tin a l a rte ria l
m a c ro a n e u ry s m ,
A - C : An arterial mac поапеитуигп caused ЕнтюггЬл^ас
detachmunt of lhe? macula (A i that was misdiagnosed .is
в melanoma. Rupture o f the aneurysm (arrow, В :■ caused
fttens-iuri or blood inlo lhe s ubrel i na I space (henialuffivUh
and eo&in slain). A periodic ac id— i ff section HCl) taken
amBcent Lo К showed whorls of fibrinous oxudale and blood
LhaL cau-sed iflfetJlnjj of Lht? retina and largely d o sed Lhe
flaplike opening '.arrowI in lhe arterial wall. Note also the
pa Lei ncy ot 1he ап еш уъm .
D and E: Arterial тктоапеигук-т causing inLrartrtiппI and
Hubrctmal hemorrhage. Note the cEiitk fitnin pi ale kit w all
ia n o w [J: surrounding lhe large detect in Lhe internal elasLic
lamina farrtrtV tj sErown in lhe elastic: stain.
IA4.. IroiT* JVrrj- cl ,tl.l: ", t- \')?7. Лпшги ;in MediL .il Ачшч.Шоп. All
n.i^hi1t n'M:rvr.4J.: L) and L, cuu rlrif-y 11ГI k hie tjl j l .
disorder characterized by mulLiple V-shaped macro­
aneurysms occurring at the bifurcation of lhe major retinal
arteries of both eyes causing exudative neuroretinopaLhy is
of uncertain etiology (LdiopaLhic retinal vasculitis, aneu­
rysms, and neuroretinopathy: IKVAN) {see Figures 6.52
and 6.33}.
Since spontaneous healing of macroaneurysms is
part of the natural course of this disorder,, treatment is
nol always indicated. The primary indication for photo­
coagulation is the persistence or progressive accumulation
of yellowish exudate in the central macular area (E'igure
й.29A-E)J,i26■■
435■
il33'^33■ <
^35'J57■
,t^s■
,iS5-,57 Moderately heavy
argon green or dye yellow laser photocoagulalion using
large-spot-size (300 imj, long-duration (0.5-second)
applications directed lo the aneurysm is successful in expe­
diting the healing of the defect (E-'igune 6.2УА-Е:) Ihis
treatment may cause a transient obstruction of the ш о у
and occasionally may cause bleeding from the aneuiysm.
Since the site of the leakage is the aneurysm, the use of
indirect treaLment con fined to the area surrounding the
aneurysm has little rationale. Surgical drainage of the
sub retinal hematoma is technically possible but has not
been demonstrated to produce visual results better than
achieved by either laser treatment or by the natural course
of die disease.i : ' if'-' it does expediate the visual recov­
ery. lhe same can be said ft)г the technique of using the
CJ-sw itched Nd:YAG laser to release sub internal limiting
membrane hematomas into the vitreous1' l0'461 or pneu­
matic displacement of the hematoma.
© T in rr

■■
' i.
RETINAL CAPILLARY DISEASES
Ihc retina normally contains very lin k extracellular fluid.
!k>mt’ diseases primarily affect the structure and perme­
ability of the retinal capiL]ar\r bed. These alterations often
result in leakage of exudate and. in some cases, escape of
blood cells into (he retinal tissue. I he content of caudate
depends ол the severity of the capillary endothelial dam­
age. Intravenous fluorescein is helpful in delecting the
structural and ротпедЩцу alterations in the retina! capil­
lary bed and the degree to which the extracellular space of
the retina is expanded (see Chapter 2J.
Cystoid Macular Edema After Cataract
Extraction
Approximately 50-70^u of the patients who have an
uneventfuE intracapsular cataract extraction will develop
fluorescein angiographic evidence of leakage of fluorescein
from Lbe parafoveal retinal capillaries [E'igure б ^ !).4^ -1' 1
More than $ 0% of these patients WUl show no biomicro-
scopic evidence of CME, and they will not have any sig­
nificant decrease in their visual acuity. 3"he incidence
of this subclinical CME. is so high that it may be consid­
ered as a normal physiologic response to intracapsular
cataract extraction. Approximately 5-15% of all patients
will develop loss of visual acuity secondary to clinically
significant CME after uneventful intracapsular cataract
extraction.||,к^ ' these patients will demonstrate the typi­
cal bio microscopic and fluorescein angiographic changes
caused by a polycystic pattern of expansion of the extracel­
lular space by serous exudation (I igures 6.32-6.34). 'Jhese
changes are described in detail in С hap ter 2. 'Jhe incidence
is much lower after extracapsular caLaract extraction and
phacoemulsification surgery. Clinically significant CM E
usually occurs within 4-12 weeks postoperatively, but in
some instances its onset may be delayed for months or
many years after surgery. " ’ It infrequently occurs before
the third postoperative week471* Blurred vision is the usual
complaint. Visual acuity is generally reduced to the range
of 20/30-20/70. A few patienLs may complain of mild irri-
Lation of the eye and show some circumlimbaE conjunc­
tival injecLion Jhe anterior hyaloid face is ruptured in
approximately 50% of patients after ittlracapsular cataract
extraction46'1 or the posterior capsule is dehisced with or
without anterior vitrectomy in eyes undergoing phaco­
emulsification. Some inflammatory cells may be present in
Lbe posterior vitreous, which typically shows evidence of
extensive liquefaction Vitreous attachmenl to the macula
12 Aphakic cystoid macular edema (CME).
A—D: Note thickening of the гласи lar region and the pres­
ence of ni-utipte cysloid spaces (A). An early angjograni
showed evid en ce of perifovBal dye leakage from the relinal
capillary bed (ht). There was some evid en ce erf dye leakage
from the optic nerve head. The dye leaked into the cystoid
spaces in the outer retinal layers and spread centrally and
poripheraiiv t ho-urafter injection (jC aftd D]. The dye stained
the fluid in lbe cystoid spaces. Note the dark stellate figure
centra 11y, the feathery margins of Ihu inlratelinal dye periph­
erally, and Ihe presence uf relinal vessels I ha I appear as dark
lines overlying the fEuorescein.
E and F: C M E following cataract extraction. The vitreous
haite partly obscured the cystoid spaces irom v ie w .(£). The
a n o w indicalcs л small yellow deposil Ivinj} deup w ilhin the
relina. M ild papilledem a was ргньеп!. Л I -hour angiogram
I.F!■showed a typical angiographic paLLem of C M E.
C —L: This African Am erican wom an w h o underwent
unevx7nlful pha ax 'm u l s-ifixation and placement of posterior-
с. hamber inlraocular len* bilaterally developed СЛЛЁ and
subretina I fFuJd in both eyes iG—J:. A ltef minimal response
to lopicnl steroids and nonsteroidals for neady a vear, she
was slatted on bra I acela^olam jde three Limes a day.
ih e responded with resolution of subnet inn I and in-trarelinal
I in id in approx iт а Lei у i monLhs. The C. M L lecu n e d in a mild
fashion after d iv onlinuation ot acela^ol amide, but resolved
on ils reinstitution IK. and Lj. She was slowly tapered off I he
acetazolam ide after another 3 months and remained stable
with 2iV2Q vision in each eye.
|fn m £ jL ^ s j| iL i U d i l u n . ’ 1 У ^ Б , A n i L 'r i c i L n 4^L.4dic.. l I A o d c i a l i l W A ll
IIi^i!'■nL'btrvuiJ. \
usually cannot he demonstrated. Mild and rarely severe
degrees of papilledema may be present. Usually there is no
optnhaimoscopLcaily visible change in the structure of the
capillary bed. An occasional small inlraretinal hemorrhage
or microaneurysm may be present.4'"-A pproxim ately
t0% of patients will show some evidence of epiretinal
membrane formation, or so-called cellophane maculopa-
thy (see Chapter 7). Over 50% of these patients will have
either clinical evidence of sysLemic hypertension or fun-
doscopic evidence of focal retinaE artery narrowing.”-"1
The eyes are typically normotensive. СМЁ after cataract
extraction appears to be more common and more severe
in patients with blue rather than brown irides. It occurs
as a complication of cataracL extraction less frequently in
blacks than in whites and occurs infrequently after extra-
capsular cataract extraction in c h i l d r e n [en5
extraction in infants is accompanied by an anterior vitrec­
tomy, significant and persistent СМЁ may occur-f"'
Kefirm! Сар/Нлп/ Dbi'uscs 5Q!
 thirty phases of fluorescein aa^Ography demonstrate
dye leakage from the parafoveal relinal capillaries, and
Later phases show the characteristic picture of CM E (iigure
6.32). Angiography can he helpful in the diagnosis of
CM E in these palients, who often have hazy ocular media
that prevent detailed biomicroscopic exam in at ion of the
Enacula. Leakage of fluorescein oflen occurs from the capil­
laries of the optic nerve head and anterior uveal trad, '['he
aqueous humor typically stains heavily with fluorescein.
СМ Ё disappears spontaneously, and visuaE acuity returns
Lo 20/30 or better Witten 3-12 mouths in two-thirds of
these patients after intracapsular cataract extraction and
no lens implant. Other patients w ill show clearing of the
edema and return of good vision from I to 5 years follow­
ing the onset of CME, The incidence of permanent visual
loss caused by CME after exlracapsular cataract extraction
and posterior-chamber intraocular lens implantation is
approximately 1-1.5IM>. The duration of CME is usually
Longer and recurrences are more frequent in palients with
a history of vitreous Loss at the time of extraction or in
those who develop incarceration of vitreous in the wound
posloperalively. Angiography of the opposite phakic eye
shows no evidence of abnormal retinal or iris vessel per­
meability except in the rare patient who has chronic bilat­
eral vitritisof unknown cause before cataract extraction.
Vitreous fiuoropholomelry in patients with aphakic
CM E shows evidence of increased ocular vascular perme­
ability that parallels the severity of the C M L ^ 1 byes with
iris-supported implants that develop CM E have a higher
incidence of developing chronic CME: and comeal edema.
ILislopathologically, the extracellular space of the ret­
ina, particularly in the inner nuclear and outer plexiform
Eayerhr is expanded by serous fluid of low protein content
(figures 0.34 and 6.35). Small numbers of chronic inflam -
maloiy cells have been found histologically in eyes with
aphakic C M E.]Sa J-:ine and Hrucker's electron microscopic
findings suggested that the cystic spaces in CM E might
be caused by accumulation of intracellular fluid within
expanded Muller cell processes.'11'1 Cass et al., however
demonstrated that CME is caused by accumulation of
serous exudate in the extracellular space, which is more in
keeping with clinical, angiographic, and Light microscopic
findings in patients wilh CME.'1""
The pathogenesis of aphakic and pseudopbakic CME
es unknown. Direcl traction on the macula by the vitre­
ous does not appear to be an important factor, '[he inci­
dence of CM E is higher in palients who have had vitreous
ftЛ Э Diagr a m il Ius Ira t ing t he b io microscopic
appearance of the macula in the presence of cysloid
macular edema.
The Eitilefjtjr buwLng uf Lhe fetinal muriate in Lhe
foveal region is caused by I hi c kem ny ul lhe ruling. The l v *-
tic pockelt of extracellular serous fluid are seen best w ilh
lelTuilluniiiTrilion.
Il-mm C a st .lrirE N(nrli>n.",l,'r t i l (№b, Arm 'ric.in M e d i a l A ™ i.ition. All
r4JH:rvtfd..
loss during cataract extraction and palients who develop
a peaked pupiE wilh vitreous adherence lo the wound fol­
lowing delayed rupture to Lhe anterior hyaloid face. Ihe
typical findings of inflammatory cells in the posterior vit­
reous of most, huL nol allr patients suggest the possible
iirtportance of inflammation. It in ay however be that these
cells are (he resull of, rather than the cause of, the retinal
capillary abnormality. Comparable inflammatory reaction
in the vitreous from olher intraocular surgical procedures
usually does nol produce Enacular edema. Removal of lhe
lens is undoubtedly a hey factor in this disease, but the
mechanism by which il leads to retinal edema is nol clear.
Diffusion of prostaglandins from the anterior segment lo
lhe retina, hyperosmolarity of the vilreous secondary lo a
ruptured anterior hyaloid face, smoldering low-grade eye! i-
lis, and vitreous traclion acting on the peripheral retina
are suggested but unproved causes of CME, l he frequenl
foldings of narrowing of the retinal arterial tree and sys­
temic hypertensioEi suggest that underlying retinal vascu­
lar d isease is also an important factor in the pathogenesis
of C M E Ihe incidence of CM E occurring following cata­
ract extraction in patients with background diabetic reti­
nopathy is much higher than in healthy patients.'1""1' En one
study the incidence of clinically significant С ML was 75 %
versus 6% of the control eyes, and lhe CME persisted for
more ihan ] year in 56% of diabetic eye*."”5 "ihe incidence
of CM E occurring in the second eye following an utievent-
ful cataract extraction in ay be as high as 5 0 % .11,4 [t may
occur soon after the subsequent о pening of the posterior
lens capsule, lhe incidence о Г CME after posterior-chain -
ber lens implantation with simultaneous capsulotomy ver­
sus that after the same procedure without capsulolomy is
probably slightly greater. '['he incidence of CME after
delayed Nd:YAC laser capsulotomy is probably Eess thaEi
] _ 2% **M 8S
H c f i r j a l С п р / Я л т у D z 's m s m 503
 ']he treatment of aphakic or pseudophaldd CMt! with
anti-inflammatory agents such as lhe anti prostaglandins
and corticosteroids may result in some temporary improve­
ment Ln visual acuity. yet there is no evidence that they sig­
nificantly shorten the duration of clinically stgjjtilJicant СМИ
or reduce lhe incidence of the development of chronic
C M E*T lbpica] nomierdiidd anti-inf] ammalorv
drops may be effective in reducing CME bul probably are
no more successful in this regard in mosl patients than
topical corticosteroid drops.'1 r~r"‘" Ihere is some evidence
Lo suggest that in some patients the increase in the intra­
ocular pressure induced by use of topical corticosteroids is
partly responsible for its Lherapeutic effect.,U! l--xcision
of vitreous that is incarcerated in the wound is of value in
some patients with persistent C M E.™ Some patients with
vitreous incarceration, particularly those xvith complaints
6f irritation and photophobia and those With many vitre­
ous opacities, do obtain relief of symptoms and improve­
ment in acuity following a Vitrectomy In the absence of
chronic irritation, photophobia, or corneal edema, vitreous
Excision from the wound is nol recommended for al least
1 year after the onset of edema because of the uncertainly
of its value and the likelihood of spontaneous resolution.
Carbonic anyhydrase inhibitors have been suggested for
the treat men I of aphakic and pseud op ha kic CM E (I'igure
6.32G-E.)
In the aphakic or pseudophakic patient presenting
with visual loss, conlacl lens examination usually is suf­
ficient to determine the presence of CM E as the cause,
i'luorescein angiography and O C I' are helpful in those
cases where CM E is not evident bio microscopically; or in
cases where an explanation of the visual loss is not evi­
dent lhe physician should remember that CM E identical
to that complicating cataract extraction may be associated
with many other disorders- some of which may have been
unrecognized before, or have developed after. cataracL
Extraction.41'' ' '' O f particular importance is de Lectio n of
the presence of a subtle rhegmatogenous retinal detach­
ment, choroidal neovascularization in eyes with other
evidence of age-related macular degeneration or vilreo-
foveal traction- that may play a role in causing the CME*
or in producing a macular lesion lhat simulates СМИ
bioinicroscopicaUy.
Cystoid Macular Edema Associated with
Rhegmatogenous Retinal Detachment
A few patients may develop the bio microscopic and fluo­
rescein angiographic picture of CMH secondary to a rheg­
matogenous retinal detachment455-511-535 CM E in ay be
ij. 'i4 HistopalhoEogic findings in a patient with
aphakic cystoid macular edema.
A : NoLe lh e tysLic spa css cu n la in in ^ serous- exudaLe in
lhe ouler plexiforrei layer afid lhe srrtalj ^рдсеь w ilh exudate
in the inner rtudear layer. Despite Ihu- marked ihickenin^
of the retina, there is liElle evidenLe of loss of neural tissue.
Note lhe s3ij>hl serous separation <H 1Еш irfe^’jla iiy thinned
11 11 piem en I epjthuiium .
u nd erlyin g r-EPl i :
ri: НкЛотк'подгдрп of л seel ion lak-ип nearer lo the CLbn-Lerof
the lovea than A. Note the arLi factitious rupture (arrow) of the
inner w ill of the lar^e ctmlraJ cyst.
IA frum ■(J.h s . iг i I Nurtfifi. " . ' 1.9£&> Лпиткмп M edical A suy ialkiri'- All
Г(дНЙ reserved.
present preoperalively or may appear initially during the
postoperative course. Angiographic evidence of the edema
has been described in 25-^0 of phakic patients who have
undergone a scleral buckling procedure and in 40-65% of
aphakic eyes undergoing scleral buckling procedures. '1
lhe incidence of CM E appears to be higher in older
patients, and in many instances it clears spontaneously
]_ale resolution of CM E is responsible for the delayed
improvement in visual acuity that sometimes occurs in
patients 6 months or longer following successful repair of
a retina] detachment. The general prognosis for spontane­
ous resolution of (he CME is good.,|J CM E has been no Led
after cryotherapy of a retinal tear in the absence of rheg­
matogenous detach ment.i; '
Cystoid Macular Edema Following Other
Types of Intraocular Surgery
Transient CME also has been observed postoperative ly
in a few phakic patients who have had other intraocu­
lar procedures, such as glaucoma filtering operations
and peripheral iridotomies. CME is a major complica­
tion afler penetrating keratoplasty.""' 11 Kramer found
a 42% incidence of clinically significant Ci-MEi in aphakic
eyes in which penetrating keratoplasty and vitrectomy
had been performed. 5]S lie found an incidence of 1 Й |
of CM E following com bilied cataracl extraction and pen­
etrating keratoplasty with a vitrectomy .md only a 4 %
incidence following combined procedures without ari
anterior vitrectomy In eyes with bullous keratopathy
and CM E with anterior-chamber and iris-supported lens,
good visual recovery often occurs after penetrating kerato­
plasty and exchange of the intraocular lens for a posterior-
chamber lens. '■L' C M E has been noted following a laser
iridotomy.,:i
Complications Following Cystoid
Macular Edema
Although visual acuity may return to lO jiO or belter after
2 or more years of CME.. н зтс patients develop permanent
relinal damage second ary to the prolonged edema, '['he
spontaneous rupture оГ the inner wall of a large central
cystoid space to form a la me! Ear hole is one of the com pli­
cations of C ^ E ,5^ When this occurs it producer a char­
acteristic biomicroscopic and a diagnostic angiographic
change (E'igures. 6.35 and &.36-). Eiiomicroscopically a
round or oval one-third disc diameter, punched-out defect
occurs in the center of (he macula, Ihe RJ?t in the base
of the hole is undisturbed. A sheen or light reflex is usu­
ally evident on the surface of the remaining retina ач a ilit
beam is moved across the hole. Yellow deposits within the
hole and a halo of marginal retinal detachment typical of
a full-thickness hole are not present. Small peri fovea I cys-
toid spaces surrounding the inner lamellar hole may be
difficult to visualize. Lite-phase fluorescein angiography,
however, demonstrates a poly cystoid pattern of dye in the
perifoveoiar area surrounding a round or oval, nonfluores-
cent, zone that corresponds with the inner lamellar hole
(E'igure 6.36E>J. ]-ollowing rupture of the inner cyst wall.,
the fluorescein can no longer concentrate in the area of the
Eamellar hole (figures 6.35 and 6.3&}. following resolu­
tion of the CM E surrounding the lamellar hole, fluorescein
angiography of die macula appears normal. Occasionally,
multiple ruptures of the inner cyst walls produce a multi­
faceted lamellar macular hole, rather than a solitary oval
or round hole.
In the aphakic patient with poor central vision and CME,
failure to demonstrate the presence of central cysts during
the iale stages [10-60 minutes) of angiography suggests a
poor prognosis caused by the presence of a lamellar hole.,
retinal atrophy, ora nonmacu lar cause for the visual loss.
Cellophane maculopathy and macular pucker caused
by epirelinal membrane formation may be evident at the
onset of CME, or they may occur as late complications of
CME. When they occur, it es less likely that central acuity
will return to normal following resolution of the CME.
Occasionally, however, these membranes may peel spon­
taneously from the surface of the retina, and good acuity
may be restored [see I'igure 7.23).
Prolonged C.VIt:. may occasionally produce atrophy of
the outer retinal layers, and the macula may appear rela­
tively normal except for the absence of a fovea I reflex.
Infant 3le Cystoid M ac и topa thy
Infantile cystoid maculopathy that macroscopically
resembled that seen in X-linked juvenile retinoschisis was
6.15 EEectron microscopic fmdings in phakrc
woman with cystoid macular edema and a choroidal
melanoma.
A—E: Before enucleation, angiography revealed evidence of
cysloid macular ed^Tim 'A and Bl. Epoxy resin-embedded
Section of [he eye (Cj revealed cystic expansion of the extra­
cellular space in the inner nuclear and outer pleKiEorm lay­
ers Ыm iron microscopic section Ihrough the edge of
one ol" the smaller cystoid spaces fD) showed the extracellu­
lar space fiIEemJ wilh homogeneous material between healthy
well-pnehervod ct»3Is. Cilvcogen ^mnules lanow.i indicate
prompt ГхлИоп I К E 5 ОСЮi. There wan thickening of (he teLi-
nal capfl-jbiV basement mum bra ne \t, X7200:.
(Prtittli Cj.iiK eL at. |i
observed on gross examination of the eyes of three pre­
mature infants of both sexes by Trese and I-qos.'""' Cystoid
changes were noted at various retinal levels. Reduced num­
bers of ganglion cells were found m the retina and central
nervous system of all patients.
Cystoid Macutar Edema Associated with
Choroidat Melanomas
Patients with peripherally located melanomas may
develop the (ypical biomicroscopic and angiographic;
appearance of CM E и nassociated with serous detachment
of the macula (Figure 6.33). ,ai 5Jj| 'E'be cause of this edema
may be the chronic inflammatory cell infiltration within
the choroid adjacent to the melanoma and retinal vascu­
litis. it is important that patients with, unilateral CME: have
a carefuL examination of the peripheral fundus to exclude
the presence of a meEanoma.
Cystoid Macutar Edema and Topical
Epinephrine and Prostaglandin Inhibitor
Therapy
Hither aphakic or phakic patients may develop the typical
biomicroscopic and angiographic appearance of CME fol­
lowing the use of topical epinephrine-like and antiprosta-
gEandin drops for glaucoma.''""^0 if CME occurs and is
caused by the drops, it can he reversed by discontinuing
the medication.
Cystoid Macutar Edema Associated with
0 c иla г Inflammatory Diseases
CME may occur in a variety of recognised inflammatory
diseases of the eye, such as pars planilis, Ekh^et's disease,
vitiliginous chorioretinitis* sarcoid os is-, idiopathic vilritis.
and scleritis.
Cystoid Macufer Edema From Other
Causes
Discussions of c m associated Kith tapetoretinal dystro­
phies. enrolld arteiy occlusion, congenital iuxtafoveolar
capillary telangiectasia, overtying occult choroidal neo­
vascularization.. and occurring after occult central retinal
vein occlusion are found on pp. 33O, 522, 570 and 58S..
respectively.
Idiopathic Cystoid Macular Edema
GME of uncertani cause occasionally occurs in one or
both eyes of patients (Figures 6.37 and 6.38A-HJ. '['he
CJML may be associaled Wilh a typical paltern of fluores­
cein leakage, or with no evidence of fluorescein staining.
5ome of these palients may eventually develop evidence of
a tapetoretinal dystrophy.
Pseudocystoid Macular Edema
Superficial changes in the retina occurring in patients with
se\-linked juvenile retinoschisis (see Figures 5.5УЛ.. С.
and F and 5.5S), -Goldmann-havre syndrome [see Figure
5.57Л. D, and II). infamile cystoid maculopathy, and rheg-
nsalogenous retina] detachment, lighLning maculopathy
(see Figure S. 16), and following spontaneous viLFeoretinal
separation (see i:igure 7 .14Г-1.) may be mistaken for GMfL
Fluorescein angiography is helpful in this differential
diagnosis. In palients With suspected GM E and a negative
angiogram, care must be taken lo exclude the possibility of
a tapetoretinal dystrophy [see Figure 5.42) and nicotinic
acid maculopathy (Figure G.38I-E.J.
Lamellar macular hofe developing in a palient
with proEonged cystoid macular edema (CME) after
cataract extraction.
A —D: Mote (Eie yellow pigment centrally lying within [he ret­
ina (aiiaw , Aj. Visual acuity was 20/40. A 1-hour angiogram
■Ы■shows a lyp ical picture of C M E. NcHe lb,]I Lhe dye fills Ihe
cenlraf cystoid spaces. Four years later 1C), thte patient has
developed a circum scribed d efed involving Lhe inner layers
or' lhe retina c t n f r ilfy. I heie was biomferascopiC evidence
of ,1л Bpiretinid membrane and cysLoid edt!mn ot Lhe retina
around lhe lamellar hole [Cl. The visual acuity was 20/70.
Angiography dtimonsl rated evidence of C M E surrounding the
lam ellar hole ID ). There was no pooling o f Che dye centrally
Ejecause H was free lo diltuse into Lhe vitreous ihruugh Lhe
defect in the inner retinal layer. The palienl died soon afler
Ihe photographs in С and D were taken.
E: Histopalholo^ic examination revealed a lam ellar hole i'l:.
epi relina I membrane i 2 ', the si it-like areas of relinal edema
in Ihe outer pfesilorm Eayer ■;31. and small pockets ot exudate
in Lhe inner nuclear layer. There was some loss of lhe recep­
tor elements i4) in the v id n ily of Lhe lameUar macular hoie
wFiere because ol postmortem artilact the receptor cell layer
is folded back on itself.
F a n d C : S c h e m a tic diagram s h o w i n g Ihe developm ent of a
la m e lla r m a c u la r hole in я palient w i l h tilvlt.
F: C M E before rupture of Lhe inlernal limiting membrane.
G : Lam ellar m acular hole with surrounding epirelinal
membrane.
i|-rHjmO.iih. '"i
L A
Nicotinic Acid Macijjopathy
Л small percentage of paLients (probably under [% )
receiving high oral doses of nicotinic acid ( 1 .S-!ig/day)
for the trealment of hypercholesterolemia w ill develop
bilateral blurring of vision caused by CM E fig u re $.381-
Lj;ia tu 3i Although the biomicroscopic appearance of
CM L is identical lo that seen in patients after cataracl
extraction, it is unaccompanied by vitritis, other retinal
vascular changes, and fluorescein angiographic evidence
of retinal capillary penneabilily alterations [bigure 6.3SK).
Cystic spaces are seen in the ouler plefciform and timer
nuclear layer on QCY.1 '*' - :(i 'lire reason for the absence of
fluorescein leakage is speculative. Whether the perineabil-
ity change in the retinal capillaries is so mild that fluores­
cein panicles do not leak out or Mil Her ceil edema is the
cause of the cystic spaces is still debated.5■ JhrompL
recovery of normal vision and complete resolution of mac­
ular edema occur after nicotinic acid therapy is stopped
(bigure 6-38L).slb-539 ReinstilulioEi of the therapy results in
recurrence of the CMb.
Dominantly Inherited Cystoid Macular
Edema
Deutman et al. described an autosomally domtnanL mac­
ular dystrophy characterized by CME, fluorescein leakage
from the retinal capillaries throughout the posterior pole,
normal electroretinographiс findings, subnormal electro-
oculographsc findings, and hyperopia."1^ F4j Atrophic
pigment epithelial changes with a beaten bronze” appear­
ance may eventually develop. Histopathologic exami­
nation reveals large retinal schisis spaces in the macula,
marked disorganization of the inner retinal layers, and
advanced degeneration of Muller cells/"111 Treatment with
oral acetazolamide has not been successful.-11 However a
somatostatin analog, octreotide acetate, stabilized visual
acuity and decreased fluorescein leakage in seven out of
eight eyes.1,411
b.17 Idfopalhic cystoid macular edema (CME).
А: (Йidpajlblc: unilateral CJMt in itie left t»ve ol Lbis man VwtiQ
wan complaininy of blurred vision. There were no vilroous
cells or biomicroscopic evidence ol" vitreomacu la* Lraction.
SteramsCqpic ллдкздгнтн showed thickening □[' Ilit? relina
cenlrally bul no fluorescein *;Гдininiq. One monlh later lhe
C M E had disappeared and ih*re was evidence of posterior
vilreous detachment.
B - D : Idiopathic self-limited bilateral C M E in this 37-year-old
wom an w ith a 4-month history of visual toss in both eyes.
Soon afler lhe onset or" symptoms examination revealed
marked bilateral C M E and onEy a few vitreous celEs. Except
Гог m ultiple а Ile v ie s her past medical history wan nega-
[Iv e . Th-u C M E failed to respond lo (png-acting prednisolone
orbital injections and oral prednisone. W h e n aeon in Miami
her visual acuity was 20/70 bolh eyes. There w ere no vilre-
ous cells. Prom iner I C M E in tbe absence o f any other abnor­
malities was presen I bilateral Ey (И and C). Angiography iLJ !'
showed no staining. Her family hisEory was negative. An
electroretinogram was normal. Approxim ately 1 month
EatfiHf she had surgery for abdominal scarring caused by
endomulriosis. Three months Liter lhe ("Mb had cleared
spontaneously.
E—G : Idiopathic, possibly congenital, nonstaining C M E in a
M-year-oEd woirffiUl with pendular nystagmus, poor vision
all her life, -find no history of nyctalopia or hem eraJopiл.
\ ler visual acuity was 20/60 right eye and 2 0 /2 0 0 JefL eye.
Fluorescein angiography revealed evidence o f slight mottled
depigmentation of lhe RPL paracenlrally -.Cl. C oIoj vision
by lshihar=t color plaLes was normal. An eleclrorelmugram
revealed mild ducrease in cOiiife and rod amplitudes w ilh the
b-wave nuich m ore atfected Lhan the a-wave.
H-L: This 55-year-oFd phakic wom an compEained of blurred
vision in her rigfil eye for Eji montEns. B io m io o s co p ic exam i­
nation reveflfcd cy-bLs in lhe right fovea |.M:■that did nol accu ­
mulate dye on angiography 11). There wore no vilreous tells,
vitrebftfVaaJ Iraction, cv other bculap paLhologv. She was on
no medications. Observation over 4 months; did not change
her ocular stalus. O p lical coherence tomography (O C T ;
confirmed persistence of cysts and revealed a pre-existing
posterior vitreous separation. She was trealed w ilh ora! acet-
a^olamide З З О т у ihree limes daiiy, the cysts resolved, and
vision relumed to 2 G/ 2 0 ( K1 by 3 months. Acetazolam ide
was Lajwferl (jver 2 months and repeal O t T 2 fLiither rvionths
laler 'Li revealed no recLiTrence of C M b .
(j. ЗЙ Idiupalhic cyslciid macula; edema (CME).

A—D: Idiopathic bilateral C M E LA and E) occurring 1 w eek

aflfr a m iIcl uiraJ-ЩЙф jfltosiruihftKrtinal :!!поьн. in an olli-efwise
heall-hy w om an, who o r awakening noted marked loss of
central vision bilaterally. Examination revealed 2СУ200 acu ­
ity. [jfomimml C M E in ppthi eyes ;A and Bj, and no bigns of
tRLraOcdbr iciГ1:агтппт:Пicvn. there wan a [jourk defined oc.]uato-
rial zone of leopard-spot byperpigjnentation in bolb eyes (Cf.
Angjoyraphy revealed a pro m3пел t slainin^ pattern typical for
C.ML (D). An oleclroretinaj’ram and peripheral visual fields
were normal. W ilh in & weeks she was asymptomatic and her
tissual acuity returned Co 20/25 right ove and 20/20 left eye.
E and F: Bilaleral postpartum CMfc and mild vitreous c e lIlilar
in fill ration in a 2 2 -ye ar-old frftrif&n w ho pitied blurred vision
3 days iiflEir a normal delivery Ы а full-term heallhy in fan I.
Visual acuily was 20/50 in :he righl eye and 20/25 in. :he lefl
eye. Two months later lbe visual acuily was 20/40 in Lhe right
eye and 20/20 in the left eye. There was an ^Jtrelinal mem­
brane in the right eye hul no m acular edema or vilreous cells
in either eye.
С and H : kliopalhic unilateral C M E in a 52-yeaf-old healthy
man with a 4-munlb history о! blurred vision. His visual acu ­
ity Was 20/30 in the right eye and 2 0 /2 0 in lhe left eye. there
were no vitreous cells. His past m edical and family history
was negative. H is findings w ere Lin e hanged 5..i yeans laLer.

Nicotinic acid maculcip;Hhy.

I- L: This 50-year-old man experienced progressive loss of
cenlral vision bilaterally. H e was receiving 3-5 grams o 1 n ic­
otinic acid a day for Lhe treatment of hypercholesterolemia.
Visual acu ily in the righl eve was 20/70, and in the left eye
was 20/.f0. The fjn d went.1 п о тта ! e*cepL for typical C M E !l
and J). Кluorescein angiography showed no evidence of ca p ­
: lary permeability in the macula (K). Six monlhs after ces­
sation o f nicotinic acid therapy, bis visual acuity returned to
20/20, and Ih e C M t had resolved iL.- bilaterally.
l-l. Iгг >iri Cijivi ':■:!■ Amerii ли lilcdJtal Aibm i.-il ii hfi. All ri^hL1.
reserved. I
Kefirm! CufvUnnf Dbi'uscs -1 I 3
P R IM A R Y O R C O N G E N IT A L
R ET IN A L T E L A N G IE C T A S IS (LEB ER 'S
M IL IA R Y A N E U R Y S M S , C O A T S '
SYN D RO M E)
Ketinal telangiectasis, a term original ty proposed by
Keese.’’” is a nonfamilial, developmental, retinal vascular
anomaly characterized by irregular dilation and incam -
pelence of lhe relinal vessels that typically occurs in one
eye of a male patient [Figures 6.3У-6.42). ''!‘ Although
primarily lhe relinal capillaries are affected, multiple focal
aneurysms of the major retinaE vessels, particularly the
arteries, may be present. Women are occasionally affected
(fewer than 10% of cases), and a few patients may show
bilateral involvement. The extent of lhe retinaE Involve­
ment and the degree of permeability alterations are vari­
able. At one end of the spectrum are patterns, usually
In fan Is or children. In whom most or all of the retinal
vessels, including the arteries and ve\ns, are telangiectatic
with massive yellow exudative and occasionally hemor­
rhagic reli пора thy and detachment of the retina. 'I his
clinical picture is referred to as 11Coals'1 disease," or, more
correctly, лCoats'1 syndrome" [Figure 6.40). Congenital ret­
inal Lei angled as is is only one of the three causes of yellow
exudative retinaE delachmenl described by Coats.131S' ^r'~ ' ^
At lhe other end of the spectrum are palients With the
retinal telangiectasis confined to a small segment of the
juxtafoveolar area. Ihese palients constitute type ! juxta-
foveolar relinal lelangiecla&is (]:igures 6.42 and 6.43).
Decompensation of these localised areas of lelangiec-
Lasis and visual loss oflen do not occur until adullhood.
Approximately one-third of palienls are 30 years or older
before the onset of symptoms.
Tallents with loss of macular funclioci may present a
variety of ophthalmoscopic pictures: [ 1 ] telangiectasis of
the capillary bed. which may or may not be confined lo
the macular area, wilh minimal evidence of intraretinal
exudation (l:igure 6.43A, G, and H ); [2) telangiectasis of
Lhe macutar capillaries With extensive evidence of intrareti­
naE exudation, Lncluditig CME\ and ci rein ate maculopathy
(t-'igures 6.431i and ] and 6.44A and EJ, (3) telangiectasis
of the macular capiHaries with extension of the exudate
Into the sub retinal space; (4) exudative detach menl of the
macula caused by gravitation of pro Lein- and Eipid-rich
exudate derived from peripheral areas of retinal telangi­
ectasis (Figure 6.ЗУ A and |); and (5) a focal, organized-
sub retinal disciform mass (figure 6.331.) or atrophic scar
(E'igure 6.33! I) caused by chronic pooling of exudate into
the macular region, oflen seen after laser or ciyo treatment
of the telangiectasis.'” " lhe latter two changes are most
often seen in infants and children with extensive areas of
peripheral retinal telangiectasis. E'hese patients often have
esotropia or an abnormal pupillary reflex caused by the
massive accumulation of yellow exudate in lhe posterior
pole [Figures 6.3 УA and D and 6.42). lhe yellow exudate
is always more prominent remote from the areas of the
6. <l'J Co nge nital ret inaEte Ian gieclasis.
Д - t : SubmvrcJlafc scar surrounded by yelltj^ ish inLnarelinal
and *ul>reLina] exudate in- ia 17-уёаг-old boy w ilh unilalw al
Efqualorial telangiectasis. NoLe lhe retinal vessels dipping
into die subneLina] scar iarrow, A I and large г т и ш у я т я and
Lelan^ieclalic vessels :I3. ihaL perfused w ilh dye (£.':.
D-F: IrUrarelinal and s-ubr^Li па I yellowish esudale in a
12-year-old boy w ilh uni Fa Lera I retinal telangiectasis involv­
ing lhe arteries, veins, and capillary bud in the paramacular
а пип \D). Visual acuity wan 2(1-400. K a le Lhe fusiform dila­
tion and Local narrowing o f lhe relinal vein (tower atrow
and aneurysmal dilation o f lhe relina I artery iupfior arrow .
Arteriovenous-phase angmgraphy сlemonsl ra LL>d aneurysmal
dilation ol the firsL-order arteriole (arrow), the capillary bed.
and the infraLemporal vein :Ы . Alter ph-otocoagulaLion, mosl
o l Ihe yellow ish exudate in Lhe macula resolved (Fj. Visual
acuity was 20Л Of).
G —I: Spontaneous resolution of submacular exudation
in a younj’ man w Ito had puor vision in lhe lefl eye all of
his lile. The right eye was normal. Note lhe sheathed and
partly occEuded relinal vessels in Lhe area of active exuda­
tion around Ihe patch of retinal lelangiectasis superior Lo Lhe
lar]ge atrophic m acular scar |H and 11 as well as elsewhere
in the fundus ( O . There w ere many areas o f occlu ded reti­
nal arterial aneurysms (arrow, H) and lelangiectalic vessels
thrbughd*jt Lhe periphery o f the Eye.
J-L: Unilateral esudnLive retinal detacEimtmL :Coats' syn­
drome) in a 2 /ч-уеаг-oJd boy caused by peripheral reti­
naE teEangiectasis HК h. The subretinal exudate resolved afler
xenon phtotucaaguEaLion o f tEte telangiectasis. Note thE
residual disciform scar in '.he macula 7 years after treatment.
Visual acuily was limited tu counting fingers at 6 foot 11.80
meters).
_ Cju „
1Л-5- und J-L.. 1гтнп (.j.s;--- , I .1
Атегк/лп Mediul Absirx i lion. All
nj^il nefit'rverS. •
retinal telangiectasis, which in some cases may be con­
fined to Lhe equatorial region (Mgure 6.3УА-С and |-L).
As the cloudy often greenish, subretinal exudate gravi­
tates more posteriorly, particularly during sleep, the serous
componeLit is reabsorbed Into the retinal vessels, leaving
the yellowish, lipid-rich residue beneath and within the
outer retinal layers (figures 6.39A and J, 6.41 C-l, and
6.41). lhe accumulation of this material in the macu­
lar region probably occurs during sleep. Over a period of
many months the yellowish exudate in the macular area
may incite lhe ingrowLh of blood vessels and fibrous tis­
sue into the sub macular exudate (Figure 6. ЗУA). Intension
of exudation Lnlo Lhe posterior fundus from telangiectasis
confined to the periphery, particularly if it is located inferi­
orly may not occur in some patients until late in life.
lluorescein angiography is helpful in defining this
structural and permeability alteration in the affected ves­
sels and in demonstrating the extent of lhe exlravascular
leakage of serous exudate into and benealh the retina.'1''1
Angiography demonstrates focal aneurysmal dilation of
lhe capillaries (figures 6.3УС, li, and E, 6.40D-K 6.42D,
L. and H, and 6.43EJ and C), retinal arteries, and veins
(Ngure 6.ЗУ С and li). The surrounding cap i Пату bed may
be dilated from slow flow and portions of the capillary
bed may show nonperfusion [E-'igure 6.4JED). I'hLs Lb par-
Licularly prominent in Lbose palients with large aneurys-
mj] Vascular anomalies in Lhe peripheral lundus. Ihere
may be some delay in passage of dye through lhe telan­
giectatic capillary bed, particularly if ihere is extensive
saccular aneurysmal formation. '['he permeability of lhe
LelangieclaLic veSseli is quite variable. Dye leakage is
Largely confined lo lhe dilated vessels. When intraretinal
serous exudation is extensive, fluorescein stains the exlra-
vascular iluid pooled in the outer layers (o produce a char­
acteristic angiographic pattern of C.Mt [E-'igure 6.44F). 'E'he
dye diffuses into the sub retinal exudale. It may nol, how­
ever, slain subrelinal exudate pooled beneath the relina
in an area remote from Lhe telangieclalic vessels. Iheyel-
Eowish exudale beneath or wilh in lhe retina will nol show
fluorescence. llcLinal function remains Умact in an area of
telangiectasis if the permeabitily of lhe relitial vessels is
relalively normal.
The natural course of relitial telangiectasis is variable.
Patients who seek treatment early in life because of exu­
dation are more likely to have more widespread retinal
involvement and develop progressive detachment and
degeneration. In some cases this may be followed by
rubeosis.. lelinal acid vilreous hemorrhage, secondary glau­
coma, and loss of the eye. Acule orbital cellulitis secondary
to transscleral movement of toxic products may occasion­
ally occur (figure 6.41 |-L.). This presentation closely mim­
ics retinoblastoma. En palients with milder degrees of lhe
disease, ihere may be fluctuations in the degree of vascular
leakage. Spontaneous resolution of exudation may occur
(E'igures 6.3?El and <3.43El-G). Patients with telangiecta­
sis confined lo several clock areas, usually in feriorly. may
gradually develop over a period of many years an elevated,
organized, exudative mass lhal may be mi&laken for a mel­
anoma or an ело phytic capillary hemangioma. En some
cases it may nol be possible lo differentiate this stage of
the disease from exudative intra retinal and sub retinal
masses caused by primary relinal capillary hem angiomas
or secondary fibrova&cular proliferation caused by branch
vein occlusion, focal inflammation, trauma, or chronic
retina] delachment (see Rgure 7.2RJ. Vitreous hemorrhage
secondary to localized areas of relinal or optic disc neovas­
cularization may occasionally occur.
Primary reLinal Lelangieclasis. is rarely associated with
clinical evidence of vascular anomalies elsewhere in lhe
body. Although congenita] telangiectasis of the cerebral
blood vessels is occasionally found at autopsy, il rarely is
associated with clinical symptoms and has nol been asso­
ciated with retinal involvem ent' Cass has seen one boy
with a prominent facial angioma associated wilh typical
retina] lelangiecLasis.
In treating children xvilh Goals' syndrome, pholocoagu-
Ealion and cryotherapy should be used whenever possible
to destroy telangiectatic vessels so as to preserve visual
function and prevent rubeotic glaucoma (figure 6.39D-Er
and J-L). Drainage of the subrelinal exudale may be
required in some cases Lo treat highly elevated abnormal
*5.4(1 Co ngeni talre LinaEteIan gieclasis associ ated w\ Ih
systemic disease.
A—F: Bilateral peripbuial and m acular retinal telangiectasis
in a E7-year-old man w ilh fa d № a p u ld r | r a e r a l muscular
dy'sLrophy. Note the macular star and esudalive relinopalhy
surrounding large arterial ,md venoLit апиитунтъ tem porary
in lhe righL eye IA Lind Li) and lhe subtle microaneurysms in
Lhe lemfwjral macula ul lhe left eye (d )L LEis visual acuitv was
2 0 ^ 20 0 rii’ hl eye and 2QS2U let! цус.*. Angiography showed
[evidence о i telangiectasis and lar^e peripheral голе o f capiE-
lary n o npLT'fusic.ni ктлротаИу in lhe ri^hl eye i.U and E. , and
rulin,il staining in Lhe paracentral area in lhe left eye I Hi.
G and H : PtfC'.iliar Lcni lateral retinal telangiectasis in a
patEbrtt with tuberous sdefttfls.
I-L: iЛчЧI Lelaniiiedasis and ewildalivfe rtflinal detachm en I
in the corcLralateral eye of a paLien-L w ilh progressive hem i­
facial atrophy (fbrrif-Rhdjfibeig syndrome I.
|C .:11 I hi. hum hn! .i.k! CJIk l-l... Iruiri Ё л п Ll al. 1 11
blood vessels. A more conservative approach is possible
in older patients who seek trealmenL later in life because
of peripheral localised detach ment or mild loss of central
vision caused by telangiectasis confined to Lhe paracentral
retina. Some patients wilh chronic cystoid edema caused
by jualafoveal telangiectasis may retain nearly nonnal
visual acuity for many yen re [E-'igure 6.4:5A-L>).' " ihose
showing progressive accumulation of yellowish exudate
in the central macular area should, however, be consid­
ered for laser treatment if the lelangiecLasis is localized
outside the papillomacular bundle region (figure 6.44A-
j -i.iKi-if:.? (Recently intravilreal anti-VEGF agenls have
been used in conjunction with laser pholocoagulalion
with the in lent ion of Irying lo decrease the accumulation
of lipid under the macula.' [ntravitreal triamcinolone
in addition to laser pholocoagulalion has also beett tried
with variable success. Surgery lo remove the submacular
lipid has been tried anecdotally ™ Macular distortion sec­
ond ary lo epi relina I membrane formation and contraction
may accompaciy retinal telangiectasis or may follow pho-
locoagulalioLi treatment. Gass has seen one adult patienl
who developed total retinal detach Lnenl and massive peri-
retinal proliferation following cryotherapy to peripheral
retina] lelangiecLasis in an eye wilh 20/20 vision discov­
ered Iale in life.
ЧЪе hislopalhology of advanced retinal telangiecta­
sis in eyes enucleated with the incorrect clinical diag­
nosis of relinobla&loma reveals irregular dilation of the
retinal capillaries, arteries, and veins and is often associ­
ated with a massive outpouring of periodic acid-bebifT-
posilive exudate into the outer retinal layers [E-'igure
6.4]D -l)J55a553'5&6'567 This outpouring is associated with
varying degrees of degeneration and disruption of the
normal relitial architecture. Retina] detachmettl may or
may nol be present. Cholesterol clefts are seen wilhin the
subrelinal eaudales and lipid-laden macrophages are usu­
ally found remote from the site of the retina! lelangiecLa­
sis. bolh beneath and in the outer layers of the overlying
retina (higure 6.4] I}. Marked retinal vascular endothelial
proliferation and hemorrhagic infarction of the retina may
occur in some children with severe retinal telangiectasis
[E'igure Й.41Л-]’).
Shields el al., in an attempt to stream line management
and understand the prognosis, have classified Coats' dis­
ease as ,l :'
* slage I: telangiectasia only
* stage 2: telangiectasia and exudation
* .stage 2A: ext rafo veal exudation
■ stage 2K: fovea] exudation
* slage 3: exudative retinal detach men I
т stage ЗА: subtotal
* stage 3R: lolaf
* slage 4: total detachment with secondary glaucoma
* slage 5: advanced end-stage disease.
Jhis staging has prognostic significance, with patients pre­
senting in stage I with almost no visual Lossr and stage 2В
with some amount of yisual loss that can be treated with
Laser pholocoagul aLion. Slage 3 had Worse visual progno­
sis.. although some could be treaLed. while eyes with slage
4 and S disease had to be enucleated.
In a recent finding, both a mother who had Coats' dis­
ease and her soil with Norrie's disease had a missense
muLation for (he N D P gene on chromosome X p ll.2 . The
same investigators also analysed relinas of nine enucleated
eyes from mates with Goats' disease and 1'ound a so malic
mutation of the retinal tissue in one of the nine cases.
Jhey speculated that Coats' disease might be the result
of a somatic mutation in the NDPffibtifc which results in
deficiency of the protein norrin. Coats' disease may occur
as a poslfertilita lic n change in the X chromosomc in a
recessive fashion, similar to Aicardi syndrome, However
6.41 Co nge nital ret inaE te Ian giectasis.
A - f: Exudative and hemtwrhagic *eLi nopal hy and fltelacEv
ment caused by widespread sever? retina Г leJangtectas is
in one (.'те o 1 a 3-yea r-oLd boy w ho had a w hile pupillary
reflex. Vision in Lhis eye Was no lighl bra^fepliontj ThtJ other
rsyc.1-was normal. Because of the possibility of retinoljiasloma.
tEie eye was etiud sated j HiStopaLh^lrajfe Btam ination of the
eye revealed prominent intraretinaI exudation and blood
fa nows, L.i, 1eJang i«.talic retina] vessels farrow, Dl, and vas­
cular t'nd<jLh(?liл1 pro-lifuralion 'L and Pi.
G - l: The eye of this, child was enucleated because o f sus-
petled relinoEjlastoma. Clinically, lh e patient aw babltf Kad a
fundus picture similar lo that in b^ure Ъ.17 I and K. Cross
examination o f lbe eye revealed a peripheral mass (arrows,
C l and inlra retinal and suWeHhal exudation exlending pos­
teriorly to the m acular area. Photomicrographs revealed
dilated relinal vessels- farrow, H )r massive inlranelinal and
subretinal exudalion w ilb i'holesteroJ cletls, lipid-Jarlen ,т}.зс-
rophages, hemosiderin, and retinal di'£>enr?ralion. Lipid-ladcn
macrophages w ere present w ithin and beneath lh e retina far
posterior to the area ol retinal teFangiecLasis (arrows, If.
I—L: Orbital cellulitis and chemosis it) simulating endoph-
Ihalmilis and rclinoblasLoma in a 2 -year-old infant with
massive subreLinal lipttproteinaceous exudation iK|- (Coats'
syndromej caused b y congenital retinal telangiectasis.
Histopathologic exam ination revealed Lolal retinal detach-
meni and marked leiangiectasis of lhe retinal blood vessels
(a nows, Ll.
1Л-1- ГгШ !) C l j i i . '''■
given that Aicardi's is an X-linked dominant condition, Lhe
mutation is lethal for mates. No study so Гаг has been able
to denionstrate a defect in the X. chromosome in Coats' or
Aicardi syndrome. "
 *7■ ' г'^г* $'■ ■
it ■■lr i *1 “ ' ■*,*-,4Л.’"
l ■

№*
 A clinical picture qI" retinal telangiectasis and Coals'
syndrome may develop in one or bolh eyes of patients
with progressive facial hemiatrophy (figures 6.40E-L
and 15.12),'"' ' in multiple family members with
facioscapulohumeral muscular dystrophy (fSUI>) and
deafness (figure 6,40А^К),55 Alport's syndrome, '”1 the
epidermal. nevus syndrome,,:ч' tuberous sclerosis (ligure
6.40G and El J , isolated hemlhypeiplasla,5^ and in
patients With reLinitis pigmentosa (figure (5.411-'-H ).™ In
one report of relinal telangiectasis in л patient With hypo­
gammaglobulinemia, Lhe retina] lesion was a cavernous
relinal hemangioma rather than telangiectasis.566-1147
lhe differentia] diagnosis in young patients with exuda­
tive retinal detachment caused by congenital retinal telan­
giectasis includes retinoblastoma (see Hgure 13.0IA-E')-
retrolental fibroplasia. IhYR (see E-'Egure 6.68), angio­
matosis retinae, JcLTCCLVirta с*тй, incontinentia pigmenli,
retinitis pigmentosa (see Figure 5.40). proliferative reti­
nopathy caused by inflammatory diseases such as pars
planilis or by chronic rhegmalogenous retinal detachment
(see Figure 7.2Й), and endophthalmitis [E'igure 6.4i]-
L) . ' " Globular, yellowish exudative detachments of the
retina secondary lo lelangiecLasis in infants and children
may simulate closely those wilh exophytic retinoblasto­
mas. Telangiectatic vessels may occur on the surface of lhe
mass lesions in both cases, hi retinoblastoma these dilated
vessels are continuous wilh large vascular trunks that
extend into the depth of the tumor, whereas the dilated
vessels in retinal telangiectasis do not exiend into the sub-
retinal exudative mass, fluorescein angiography may be
helpful in establishing the diagnosis (E'igure 13.01A and
f). Ultrasonographic demonstration of calcium in the
eye with retinoblastoma is also important in this regard.
Patients with localised congenital telangiectasis associ­
ated with retinal arterial and venous aneurysms may be
misdiagnosed as cavernous hemangioma of the retina
(see E'igure 13 16A-C), acquired arterial macroaneurysnis
(E'igure 6.23), branch vein occlusion [see figure 6.Б1С-Н),
and bilateral multiple retinal arterial aneurysms associated
with neuroretinilis (see figures 6.52 and 6.53}. [See a later
subsection for the differential diagnosis of type E juxtafo-
veolar telangiectasis.)
Facioscapulohumeral Muscular
Dystrophy and Coats' Syndrome
Г5111) is an aulosomal-dominanL disorder with a variable
age of onset from childhood to old age, and severity from
mild weakness to severe disability. A family history may be
difficult to elicit because expression of the gene is variable
and penetrance is incomplete. Jhe characteristic clinical
features include wasting of the shoulder girdle, upper del­
toid, pectoral is, biceps, and iriceps muscles, with relative
hA'2 Coals'disease,
A—E: Hi is 36-year-old male noted trouble w ilh his vision on
lhe га£=Ы J т о п Iha previously. H i? vision whs 3/2 OQ on lhe
riн,4пI and 2 f'li) on lbe left. In the sLiperolttmpuraI quadrant
3-4 rlisc antias of relinal lelanj^ieclasia with hemorrhages sur­
rounded by dense druinate lipid exudates and retinal thick­
ening w ere seyn Anulher patch w as present nasallv.
Angiogram showed the bulbous vessels, c.apillarv nonperfu­
sion, SLcrrou nd i nu. di 1. 1Led capillary bt'd, and leakage from the
lelan^ieclalic vessels '13 and El. H e underwent laser Irual-
inent and moved lo Texasj
Coals' disease with reUnal degene ration L
F-H: Л 72-year-old man, follow ed since 19EO Irom age 45
for rhinitis pigmentosa, initially presented w ilb retinal .and
vitreous hemorrhage in the right eye, requiring pars plana
vitrectomy X 3 Find phacoemulsification c.a(arat:t surgery.
Thai eye Lurned phLhisical. The left eye has had several epi­
sodes of vilreous hemorrhage and received laser trealmenl
(F-H).
I - H , rjburtm .-y " I 3>r L ,i j n ' h L i 1 W . A r t 'r u l .
preaerygtion of the lower deltoid and prominence of the
upper trapezius muscles. Muscle weakness can progress to
the trunk and lower limbs over lime and 20% can become
confined to the wheclchair. l.oss of tone of the abdomi­
nal musles leads to a protruding belly, and of the facial
muscles lo a drool and protruding tongue. iefl [.eg muscle
involvement can lead to tiptoe walking and foot drop,
resulting in an unstable gail. I joss of vision caused by reti­
nal telangiectasis and deafness (high-frequency hearing
loss) occur in some of these patients and rarely may be the
initial manifestation of f'SUD {figure 6.40A-fJ.’1’ v ',:-1:х,_
5io.>h E&iijr onsel of symptoms and deafness herald
more severe cases. Myoclonus and temporal-lobe absence
attacks can occur. Unlike congenital retinal lelangi-
ectasisr bolh eyes are affected and both sexes are affecLed
equally. ЧЪе onsel of visual loss is variable and may occur
in early childhood. Asymptomatic family members with
minimal evidence of E-SI ffi may show evidence of retinal
telangiectasis wilhoul evidence of exudation. 'iTie patients
and family members should he screened for evidence of
retinal telangiectasis si nee early treatment with photocoag­
ulation may prevent visual loss. A young girl's presentation
wilh neovascular glaucoma al age 2 led to the detection
of bilateral Coals' disease; further onset of seizures led to
lhe diagnosis of P&HD,5^ Croats' syndrome has also been
reported in a scapulohumeral muscular dystrophy that is
probably is a variant of f 51 ID .-’75
IV ld in n ,;i lhe l<i]ig a:r.i c-:' . |-к|ЗЛ) h
the locus for the gene for 151ГD; however the exact gene
has not been found .'"11’'1
C O N G E N IT A L A N D A C Q U IR E D
ID IO P A T H IC M A C U L A R R ET IN A L
T E L A N G IE C T A S IA
Adult patients may develop loss of central vision caused
by exudation, dt ITu.s.ioп аЬп^ф а1Щ ^ or from isch­
emia ,ind nonperfusion of ectalic and incompetent
relina] captUдrles that are confined to lhe fovea I and peri-
foveal region, which are either congenital or оГ unknown
c a u Thei £ palients Щ into several
subgroups. Since lhe extent оГ die telangiectasia may vary
and extend beyond lhe fovea, "macular telangiectasia"
appears lo be an appropriate name.
Croup 1A: Unilateral Congenital
Macular Telangiectasia
Patients wilh unilateral congenital fovea I and parafoveo-
lar telangiectasis probably suffer from a localized mild
form of congenital retinal telangiectasis, a nonfamilia!
disorder affecting predominantly one eye of maies with­
out other evidence of systemic disease'1' 351 [see pre­
vious discussion of congenital retinal telangiectasis and
Coats' syndromej. lhe localised form of congenital reti­
nal telangiectasis is typically confined lo an area between
I V i and 2 disc diameters in the temporal half of lhe mac­
ula , where il straddles the horizontal raphe [E'igures ^.43
and 6.44]. ,(,i Approximately one-lhird of patients will
have some focal telangiectasis in the extramacular area,
usually temp orally. Yellow, lipid-rich exudation is usu­
ally present at the outer margins of (he area of telangi­
ectasis, often in a ring con figuration (figures 6.43], and
6.44A and t). The mean age of onset of symptoms is
approximately 35 years. Polycystic macular edema and
exudation are the cause of the loss of acuity, which usu­
ally ranges from 20/25 lo 20/40. Telangiectatic capillaries
are easily visualised wilh bio microscopy and fluorescein
angiography. Blunted right-angle venules, superficial reli-
naE crystals, intrarelinal pigment plaques, and sub reti­
nal neovascularization, features of group 2 fuxtafoveal
capilSary lelangieclasis, are not found in these palients.
1-arly-phase stereoscopic fluorescein angiography shows
prompL filling of the lelangiectalic vessels, affecting both
the superficial and the deep capillary network, and late
intra retina] staining, ihe natural course of this disorder
is variable, bome patients may retain excellent visual acu­
ity for many yeare in spile of chronic waxing and waning
ti.43 Natural course of congenital juxlafoveolar retinal
telangiectasis, group 1A„
A - D : Tbiк r>2 -yuar-ojd man noLed blurred vision in lEie 1йА
eye. Hi 5 visual acuity in [Ьы Ifit eve was 20/30. The right
eye was nominal. .Note lhe localized zone o i capillary Cel-
,1n^ieclatis, w b id i was confined lo die juxlafoveoiar region
terriBoraEEy [arrows, Aj. Angiography demonstrated the lelafi-
^iectasis i]f) and showud evidence (if cysloid m acular edema
fCIJ. N o treatment was giver. Twelve years later Eie bad deveE-
uped some lipid feKudatiofi (□ ) and his visual acuily was
20/40.
E—I: Spontaneous resolution о! с ire inale m aculopalhy caused
by juxtafoveolar retinal (elangieclasiv occurred in л lb-year-
old Ixa. \vl'o v. lic r !k-v.'.is inili.ilk in I h.id ri.irki ■
exudative maculopaLhv ;Ll; bis visual acuity was ijppnoxi-
matelv 2 (>/1 0 0 . i i * years later Lbe exudate had cleared, be
was asym plom aIic, and bis visual acuity was 20/20 I.F and CJ>.
Angiography demons! ra led "Ehil ihu telangiectasis extended
into the p e iifjh tra I lundus temporally lH:. AL age ЗЙ years he
noted decreased vision in the right eye. His visual acuity was
20/50. Note tEie recurrence Dt the lipid exudation (Ip.
]-L: This 57-year-old глас presented with a Ь-vear history of
blurred vision in the left eye and a 2 -week history of blurred
vision in lEie righLeye. His visual acuily was 20/20, right eye,
and 20/30, left eye. He bad bilateraE juxtafoveolar telangiec­
tasis associated with mr3d cystoid edem a but no lipid exu­
dation in Ejotti eyes ■! . Ten years later his visual acuity was
20/30, ri^ht eye, and 2Q/40, left eye. Note the temporaE loca­
tion of tEie telnn^iectalk capillaries .uirl the lipid exudate [K
and L}.
CMJi (flg iiiE 6.43A-1J."'15w Those wilh yellow lipid exu­
date in or near the cenler of the macula are probably al
grealesL risk of developing progressive loss of visual acuity,
focal applications of laser pholocoagulalion of the telan­
giectatic vessels may be helpful in restoring and preserving
cenlral acuity (I'igure 6.44А-И). Congenital telangiectasis
confined lo lhe capillary bed in the region of the macu­
lar area should be differentiated from idiopathic bilateral
acquired juxtafoveal capillary1 telangiectasis (figures 6.45-
6.43),55L-556-SlH,Jsa5M and telangiectasis caused by branch
vein obstruction (see figure 6.79[>-К]. diabetic reti­
nopathy (i'igure 6.52A-C), X-ray Irradiation retinopathy
(figure 6.57), tales' disease,^1"-’ i: sickle-cell maculopa-
thy. tuberous sclerosis [Figure 6.40C and El), and carotid
artery o b stru ctio n .: Croup lA palienls should be
clearly differentiated from patients wilh dilated peri fovea I
capillaries and evidence of vitreous cellular infillralion,
whether it is caused by acquired inflammatory disease or is
part of a tapetoretinal dystrophy.
Croup 1 B: Unilateral, Idiopathic, Focal
Macular Telangiectasis
Most patients With unilateral idiopathic focal juxtafo-
\t-oLir telangiectasis are middle-aged men who have mi3d
mctamoFphopsia or bSurring caused by exudation from a
minute area of capillary telangiectasis that ее usually con­
fined lo 1 hours of the clock or leas at the edge of lbe cap­
illary-free zone [l:igurc 6.441—Lj. ,L,| ',:'Ll Et may or may not
be associated wilh a Small amounl of yellow exudate. The
vIsu-lTI acuity is usually 20/25 or better. Angiography shows
the focal capillary telangiectasis ,ind minimal staining.
i Nhotocoagulalion is usually nol advisable because of the
pFOKimity of Lbe leakage to the capillary-free /one and the
good visual prognosis without treatment. Et is uncertain
whether this is an acquired lesion or merely represents a
minute focus of congenital telangiectasis.
(j.44 Co ngen ilaE j uxta loveolar reti n al te Iangiectasis,
group IA,
Л—D: Retinal telangiectasis involving the capillary bed
1етрогаГ to I by macula as-soCi'ated vw-il К л localized serous
detpn.hmen1 of I lit? letina, relinal edema, and cirunaLe reLi-
nopalhv in а 27-year-old n u n i.A). K o 1e Hie shea I bed cap il­
laries j-u-sl. 1с?трогл I I о Iho macula Iл now ). The HevaUflt) of
Iha lesion was tensed primarily by :hkkening t>l" lbe retina
sfcotidary Lo edemaj Angiography revealed OKlensive leian-
giectatk: involvement of the capillary bed lemporal to Lho
macula 113- and Cj. 1bn-re was- marked leakage ot dye from lhe
capillary bed in lho area sunoundod by circ inale relinopa-
ihy |C 1. Note lho partial dad: figure :n lhe гласиI.ч 'arrow*.
Twelve monlh.1. after яепо-п phoLocoagulalion, the ejiudato
bad cleared (D) and V Ih ^ J acuity was 2 0 /2 0 .
F- H : Uni literal сопрел i La I juxLafovoolar telangiectasis ir>
lho rij’hl eye iL- and F) of this 49-v'oar-ok iran, whoso visual
ntuily was 20/50. Following focal argon Inser pholocongula-
tion his visual acmLv improved I о 2Q-'20 and the uxuda[]on
resolved ;Hl.
Congenital monocular focal jtndafoveolar retinal
telangiectasisr group IU.
I and J: This 40-yuar-okl man noled blurred vision in the
right eye caused by exudalion from <i total area of capillary
telangieclasis iarrows, I and | a 1 the edge of lhe tapillary-
frue jo n e al 1 o'clock.
К anti L: This boallbv 2 fi-year-old ™ n notod metamorphop-
sia in lho loft eye t aused by yoJJcjw oxudaLion from fo Q l reLi-
naE lelanyieclasis confined to a small area at the cdjje o f lhe
Capillary-free! ionti.
Croup 2A: Bilateral, Idiopathic, Acquired
Macular fluxtafoveolar) Telangiectasia
Mosl of these patients are in the fifth or sixth decade of life
(mean age 55 years) when they seek treatment for mild
blurring of vision in one or both eyes.'1 both sexes are
equally affected. PaLients with group 2A telangiectasis typi­
cally demonstrate bilateral, symmetrically small areas, usu­
ally 1 d isc di ameleT or 1ess, of occul l capi II ary tel angteclas is
that involves and may be confined to the temporal half of
the foveolar areas or may include pan or all of the nasal
para foveolar areas (figures 6.45 and
]"his form of telangiectasia is associated with minimal
intraretinal serous exudation and no evidence of lipid
exudation. Visual acuity Is typically 20/30 or better when
persons initially seek treatment. Hiomicroscopically, the
development of (his disorder can be subdivided into five
stages. !n stage 1, usually found in the fellow asymptom­
atic eye, bio microscopy demonstrates no abnormality,
lhe early phases of sleieoangiography show minimal or
no evidence of capillary dilation, and late phases show
mild staining at the level of the outer parafoveolar retina
temporally En stage 2 there are slight graying and loss
of transparency of the para foveolar retina and minimal
or no telangiectatic vessels (Figure 6.45A and D). Farlv-
phase angiography reveals evidence of mild capillary tel­
angiectasis affecting primarily the outer capillary network
temporally (Figure 6.45В and C). En stage 3 there is bio-
tnicroscopic evidence of one or several slightly dilated
and blunted retinal venules that extend all right angles
into the depth of the parafoveolar retina. These are usu­
ally first evident temporally. Stereoscopic angiography
often shows unusual capillary dilation and permeability
change in (he outer relina beneath one or more of these
venules (Figure 6.45EJ-1:). A peculiar linear branching pat­
tern of these capillaries occurs in some patients (figure
6.46H-D). In stage 4, one or several stellate foci of intra-
retinal black hyperplastic RPli envelops (he posterior
extension of the right-angle venules [E'igures 6.45J-L, and
6.46A and L). I'hese intraretinal pigmented plaques have
a characteristic appearance that should suggest the correct
diagnosis, even when the telangiectasis cannot be visual­
ized bio microscopically In stage 5, biomicroscopic and
fluorescein angiographic evidence of type 2Л subretinal
neovascularization occurs in the para foveolar area, often in
Lhe vicinity of the intraretinal pigment epiLhelial tnigralion
(E'igure 6.460 and l-L), Multiple, tiny, golden, crystalline
deposits develop near the inner surface of the parafoveolar
retina in approximately one-half of the eyes in stages 2-5
fc.45 Bilateral acquired juxlafoveolar lelangiectasis.
group 2A,
A —C : Bilateral, acquired, paraloveoEar capillary telangiecta­
sis in л 59-уеаг^йш man With a 3-year hi story of mild blur­
ring of vision in both eyes. His pasl medical history and
family history were negative. Visual acuity in Che rFghl eye
was. 20/20: the left eye was 20/30. He had nasal paracen­
tral scotoma la in botii eyes on Amslcr grid testing. There was
slij’hl graying of Lhe juxLafuvunl reLina temporally in boll:
eyes (Ah. N o dilated capillaries w ere visible. Angiography
ffivealfed early leakage of dye from Ihe relinal capillaries or:
the temporal sidE! o f the m acula bilaterally (C).
D -F: Acq .lined juxtnloveolar telangiectasis and foveolar
atrophy in a 4 2 -year-old wom an w ilh a 2-monlh history of
painless progressive loss of vision in bolh eyes. A general
medical exam inalion was w ilh in normal 11mils. The fam­
ily his Ion 1 was negative. Visual acuity in lhe rij^hl eye1 was
2 0 Л 0 0 and in llie lefl eye was 2 0 3 5 . There was a fainl J^rny
halt) in fiolh m aculae ■;[?!. Angiography revealed evidence
et" mild peri foveolar capillary telangiectasis -I: and ^ and
paracentral fluorescein staining bilaterally. There was no e v i­
dence of cystoid m acular edem a (C M E } centra.! Ey.
G —I: Acquired, bilateral, juxtafuveolar telangiectasis and
CVlL in a 54-year-оid surgeon wiLh a 10-year hislory of mild
blurring of vision and melamorphopsia ihal w ere worse in
the right eye Ihan in lhe lefl eye. His visual acuilv was 2(1'25
in both eyes. Nole the halo o f ^дау discoloration of Ihe peri-
foveolar retina and the y e llo w spoL centrally {C }. The appear­
ance of lhe fell m acula was similar, except there was no
central yellow deposit. H is past m edical hislory and family
hislory were nugalive. Angiography shewed bilateral jusla-
foveolar telangiectasis and evid en ce of peri foveolar retinal
staining that did not extend ini о the central m acular area 13-1
and ll.
J-L. Acquired. :iI.i:: ■I juxNUoveola angi^t-isi-. :n .i
6 .1 -year-oldwom an who had a hislory of telangiectasis for fr
years aL Ihe time ol the photograph in J w hen she had super­
ficial retinal crystals and one small stellate retinal pigment
epithelium lesion (arrow, J}. O ver a period o f 4 years, she
develofied multiple areas o f stellate pigment ftiijjration into
Ihe relina (arrows: around lhe right-angled venules draining
the telangiectatic capillaries in both eyes Ik and I ) . Nolo Lhe
small superficial punctate white retinal crystalline deposits.
Her visual! acuity w hen last measured w as 20/50 in the ri ghl
eye and 20/Д0 in Lhe lefl eye.
|A—( . fmm ibml t?ViiLm.t.^|rl.. t j £$62, AinL'rk.sn Medltal
AMry.j.Mujn. All ri^bls: fH^ervtd ■
(Figure 6.46A, F, and G-l). Approximately 5% of patients
may develop a round, yellow, intraretinal spot 100-300(im
in diameter in the center of the foveola in one or both eyes
(Figure 6.45t;). Ihis is usually associated with minimal
loss of the foveolar depression.
 QCFahows one or more cysls or lacuna in the inner or
outer relina in all stages of the disease [E'tgure 6.47H and
I). These cysts or lacunae may be the result of breakdown
and loss of lhe Waller cell bodies in the MO Her cell cone
and the rest о Г the fovea.
Visual acuity is usually normal in stages 1 and 2. Most
patients become symptomatic at stage 3, and some main­
tain good acuily after developing stage 4. Loss of central
vision in these patients typically occurs slowly over many
years and is associated with atrophy of the foveolar relina
that develops in the absence of typical СМ И Jhis atrophy
tnay produce a picture simulating a lamellar macular hole
(E-'igure 6.46E: and h j.'11, fluorescein angiograpEty in stages
1-4 fails to show late staining extending into the center of
the fovea in all but a few eyes that develop angiographic
evidence of capillary ingrowth into lhe PAZ (E-'igure 6.45J E
and J). PC T demonstrates some degree of thinning in
almost all palients and is extremely useful in confirm­
ing this observation made by Cass. Cystoid edema, yel­
low exudater and loss of the foveolar depression develop
only in those patients who develop subrelinal neovascu-
Earizalion (figure 6.46G-L)/hHt This complication may
be associated with rapid loss of vision, subrelinal hemor­
rhage. disciform scarring, and relinocboroidal anastomosis
(Figure 6.46C-L).
The yellow fovea I lesions in these patients may be mis­
taken for those seen in the adult form ofvilelliform foveo-
tnacular dystrophy {see Figures 5.QS and 5.09) oi Best's
disease {see E:igures 5,01 and 5.02). 'I hose with stellate pig­
ment plaques or with choroidal neovascularization may
be misdiagnosed as having senile macular degeneration or
chorioretinal scare secondary to focal choroiditis.
rii&lopathologic examination in one patient with group
2A telangiectasis reported by Green and coworkers showed
focal thickening of the sensory retina in the parafoveolar
region, Lhickening of the relinal vessel walls, evidence of
t>. EJila tera I acquired j u xtafoveo la r lelangi ectas i s,
group 2A,
Л -E: Th 5 wom an first noted loss ol central vision at age 50
yean-. Al thaL time her visual acuity was 20/25 bilaterally
1 here was mild loss of Tolinal transparency and superficial
relinal c r y s ta l in lhe juxtafoveolar region lumporally in Ьо 1К
eyes (A . Stei’aaiCopjc angiograms rriA^aled evideirtCe o f jux-
tafoveal telangiectasis in both eyes temporally and evidence
erf a peculiar rtHnadelinjj o f cl i Ia led blood veisels in lhe ouler
retina in the left eye ( B—EI>h. W h e n sEie returned 13 years later,
visual acuity was 2 Q/2 O0 r right eye, and 20/30, left eye. She
had developed stellate foci of inlraretinal retinal pigment
epi I helium hyperp3asia temporally in both еун» (E). Note the
mullipie, superficial, pale yelJdvy crystalline deposits, ,im,J
the focal atrophy o f the relina central Ey simulating an inner
lamellar hole.
f : Thiы woman hnid bilatemi .required jjujttafovteolar relinal
tel л n l; iecLisi я. Mote lEie sharpk deJmcaLed fovedlah atrophy
simulating л macular hole.
G-L: This 3 6 -yea r-oEd man was being observed because
of mild blurring of vision caused !iy acquired, bilateral,
peri foveolar telangiectasis, before developing marked
metamorphopsia in Lhe ri^ht eye caused Ijy subnetinal neo­
vascularization (G). He was asymptomatic in the left eye {Ht.
Note the prom iпел I superficiai crystalline retinal opacilies in
belli eyes iC.1 and M l S k yeart laler in the left eye he devel­
oped subrelinal neovascu lari ja l ion fl-K; ihal resulled in a
lar^e disciform scar ■L.l.
I t ] - I., Ггигп L i i K . .in d r j'.-.lk.LW.I ". О I .-VИК Т -I ilrl ,'vk l I L-I
Aiibcialmn. All ni^hlK J4!st'rv<;c( 1
capillary endothelial abnormalities, but minimal or no
evidence of capillary telangiectasis [figure 6.4Й).'" In a
review of histopathologic sections of the eye previously
reported by Creep and coworkeis. Gass found evidence of
retinal capillary invasion of the retinal receptor layer and
minimal evidence of cystic accumulation of extracellular
fluid (E-'igure 6.4SH-!])
 I low do we account for the fetlnaj staining and lhe
absence of evidence of mlgralioEt of extracellular iluid
Into the central macular region to form cystoid edema in
patients wilh group 2A juxtafoveolar Lelangieclasis? '['tie
("oilawing sequence of events appears to occur (Figure
fi.47JJ. Larly fluorescein staining of lhe thickened capillary'
walls, particularly those in the deeper plexus, is responsi­
ble for the early-phase angiographic appearance of "telan­
giectatic" vessels. lhe altered structure of the capillary wall
is associated with decreased metabolic exchange and mini­
mal increased endothelial permeability. These changes
result in low-grade chronic nutritional damage lo the reti­
nal cells, particularly those al the level of the Inner nuclear
layer that includes the Muller cells. The lale diffuse stain­
ing that stereoscopically appears to occur al the middle
anti ouler retina is probably caused by staining of minimal
amounts of extracellular matrix and intracellular diffusion
of fluorescein into damaged retinal cells. Further changes
In the outer capillary bed, which may include capillary
proliferation and invasion of the outer retina and occa­
sionally the foveolar retina, are accompanied by alteration
of the pattern of venous outflow and formation of dilated
rigjit-angjed venules (Hgure 6.47Jr stage 3). Nutritional
deprivation of the retinal cells In the middle retina, partic­
ularly the Muller cells, leads lo degeneration and atrophy
of these cells and the connecting photoreceptor cells, 'litis
loss of photoreceptor cells is responsible for the gradual
loss of visual acuily and biomicroscopic picture that may
simulate a lamellar macular hole. Loss of photorecep­
tor cells permits KFIi cells to migrate inlo the overlying
retinar particularly along Lhe right-angle venules, lo form
black stellate plaques [Kigure 6.47], stage 4]. Stage 5 dis­
ease results when loss of relinal cells induces proliferative
changes in the deep capillary network that may eventually
gain entrance into the subsensory retinal space, where a
type [I pattern of sub retinal neovascular growth and reac­
tive proliferation of the RET- occurs (Kigure G.47|, stage
5). Although il is probable that Lhis neovascularization
6.47 bilateral acquired juxtafoveolar telangiectasis,
group 2A wilh good vision and lacunae.
A —I: l'hih 67-year-dld womian noled a change in ihtir vision in
her right eye in 2004 Lo 20Л40. She saw 20/20 w ilh her lefl
eye. Both foveas had fine telangiectatic vessels, no pigmen­
tal ion, cryslals от befifljflfrhagps :A and Hi. Anyio^ram was
consisLenL with Bftempnral hypefflUorescertEe and slaining
erf Linkup IС and D). Hour yearn later her visjon continues lo
remains at 20/40 righL and 2 0/25 lefL eye. She now bas a few
Ejigmelrl figures in Lhe lefl fovea fF and G . O plical coher­
ence tomography shivs lhe lypical lacunae seen in [his l o h -
dilion likely from change^ in the M u lle t cell cone :H and Ij.
J: Diagram of presumed analom ic changes Hiccompanying
stages 3, 4, and 5 of developm ent ol acquired fuxLa foveolar
Lelan^iecLasrs involving lhe deep relinal plexus.
SLage 3, IncompeLent retinal capillaries, sw elling ol the
nelina on lbe left side of the fovea, developm ent o f dilated
rigjit-anyle venules (RaVj draining lhe deep capillary plexus
(DCfVj and early proliferation ot capillaries inlo [he outer rel-
inal layers-. Arrow indicates superficial relinal crystals.
iLage -t, Alrophy of ouLer reJinal layers, lnyperpJaHia o f Lhe
relinal pigment epi I helium (RPtf, inLrarelinal m itral ion of
R PE cells alongside the KaV, further proliferation and remod­
eling ol" lhe LJCIJ.
SLa^e 5, Type 2 subretinal neovascularization, subrelinal
bleeding, and exudation, lh e subretinal new vessel я m ay or
may not ana-sLomoso with lbe choroidal vessels.
is primarily derived from the retinal vessels, evidence of
chorioretinal vascular anastomosis may eventually occur.
The cause of the golden refraelile structures at the inner
retinal surface In the juxtafoveolar area is unknown, 'I heir
appearance suggests diat they are lipid. Their Eocalion in
the region of the internal limiting membrane of the retina
suggests LhaL Lhey may be a product of degenerating Muller
cells whose nuclei are Eocaled in the inner nuclear layer
at the sile of the altered deep retinal capillary plexus, and
whose fool plates form Lhe internal limiting membrane. il
Ш ьЖ
'j V l
 The cause for group 2A telangiectasis, which is lhe люьЕ
com [non form of idiopathic juxtafoveolar teSangiectasis, is
unknown CJhronic venous sLasis caused by obstruction of
the retinal veins as they cross the retinal arteries on bolh
sides of the horizontal raphe may be a factor.1,011 More
recently, study of the FAZ using whole mounts at 26-41-
week gestational age has shown that the vessels making up
the lemporal FAZ are the last to close in lo complete lhe
ring.1,: lhe lemporal juxtafoveolar vessels are the earliest
vessels to he affected in type 2 juxtafoveolar telangiectasis.
Whether there is a relationship between these two features
is interesting and needs further exploration. Although
approximately 15% of" these patients may have evidence
of system fie diseases Including systemic hypertension, bor­
derline diabeteSr coronary artery disease, and renal failure
associated with Alport's disease, long-term follow-up stud­
ies have failed lo link group 2A telangiectasis to systemic
disease in the majority of patients.iS] Familial cases of
group 2A telangiectasis occur occasionally.
Patients vrtlh group 2A telangiectasis should be differ­
entiated f r o m cases of bilateral retinal telangiectasis with
other causes, including bilateral group I A congenital jux-
Lafoveal telangiectasis (higure 6.43J-L), juxta foveal telangi­
ectasis associated with tales' disease (see figure 6.62A - 1!),
diabetes met!Hus, and irradiation retinopathy.
There is limited in formation available concerning the
results of photocoagulation treatment of group 2A telan­
giectasis. It Is probable that photocoagulalion is ineffec­
tive In restoring visual function in these palients before the
development of subretinal neovascularization because loss
of function is associated with retinal atrophy rather than
inlraretinal exudation, as in the case of group 1 teEangiec-
tasis. a5 EL is also unlikely that prophylactic photocoagula-
tlon of the paraccntral retinal capillaries will eilher slow
or prevent the loss of visual acuity. In mosl instances the
close proximity of subretinal neovascular networks to the
center of the fovea precludes photocoagulation as a means
of restoring or preventing loss of central vision.
Croup 2B: juvenile Occult Familial
Idiopathic juxtafoveolar Retinal
Telangiectasis
|uxtafoveofar retinal telangiectasis similar lo group 2A, but
w itbm i evk v:ia- ol righ:-.ingle vm Liles superJkLi] relina!
refract lie deposits, or stellate pigmented plaques, has been
reported in Hvo siblings, 3 and 12 years of age.
Croup ЗА: Occlusive Idiopathic
luxtafoveolar Retinal Telangiectasis
Croup ЗА patients experience variable degrees of loss of
cenLral vision in both eyes associated with juxtafoveolar
6.4Й Spontaneous retinal hemorrhage In bilateral
acquired juxtafoveolar lelangiectasisj group 2A,
A-D: This 65-year-old asymptomatic wom an with vision
of 2СУЗО in ea( h eye when seen ftл a rouline exam was
found I о have bilateral foveal lelangi ectasia ■wilh fine ini ra­
re! in л I pigment, and ,i flock of bkwid in Lbe superfit ial relina
in her lefl eye. An an^iajjram revealed Ihe typical patient
01 staining c l the intraretinal tissue, but no tale pooling of
dye. O ptical coherence tomography did nol reveal inlra- or
ни brut ina I IbicltCfpfng or fluid (IJ.i. N o Irealm cnl was given
and lbe retinal hemorrhage disappeared by 3 months.
Examination 13 monllis lalei revealed no change in vision,
or si^nsor subrelinal neovascular membrane ID:-.
Clinfcopathologlc correlation of bilateral juxtafoveolar
retinal telangiectasis, group 2A.
E—H : This 5S-year-otd wom an, whose visual acuity was
2 ОС л in both eyes, had an^io^raphit evidence of intrareLi-
naf lluorescein slaininj* in the lempora! u^talovnolar ruj^ion
bilaterally lb ■Liglil m icm scopy revealed local Lhickeningof
the retina in the juxtafoveolar area (F}. Com pare lhe normal
relina on lhe null I side o f Lhe arrm v in И vviLh Lhe affected
retina on the left side o f Ihe arrow. The ganglion cells appear
vacuolated and swollen. There is m inim al evidence of ;ocal
net uniuIalion of extracellular iluid in lhe inner nuclear and
■outer plexiform layers. 14igher-pawer views of the affected
relina showed uvidunce of focal invasion of the nerve fiber
layer of H enle and the receptor cell layer w ith fine capillar­
ies i.arrcjws. С and Hi. The retinal piemen I epilholium and
t hiiroid w ere normal.
It .ITfJ К Гшгп(j[H 1 tl .hi.' -l'I
retinaE telangieclasis and progressive loss of the jLLXta-
paplllary capillary network In later life associated with a
variety of systemic diseases, including polycythemia, hypo­
glycemia, ulcerative colitis, multiple myeloma, and chronic
lymphatic leukemia [E:igure 6.4УА-^].55,-®а The macular
changes In ihls group are similar to those that occasion­
ally occur in patients with sickle-cell retinopathy diabetic
retinopathy (Figure fr.52), and X-ray radiation retinopa­
thy (J-igure 6.57B and Dj. 'Lbe loss of central vision may
be abrupt and be associated with ischemic whitening of
the relina centrally, occlusion of the peri foveolar retinal
capillaries, and minimal evidence of telangiectasis, which
develops only taler {Figure 6.51 A). In others the loss of
para foveolar retinal capillaries may occur slowly and be
associated with telangiectasis of Lhe adjacent capillaries,
probably as the result of development of collateral path­
ways of flow.
Croup 3 B : Occlusive Idiopathic
Juxtafoveolar Retinal Telangiectasis
Associated with Central Nervous System
Vasculopathy
Croup 3JS patients have a hereditary oculocerebral syn­
drome characterized by the onset in middle or Iale r life of
progressive loss of central vision in both eyes caused by
progressive obliteralion and telangiectasis of the peri fo­
veolar capillary network, which in some patients is asso­
ciated with optic atrophy, abnormal deep lendon reflexes,
and other evidence of central nervous system involvenienL
[Figure ! 14д|н ь а д 1и о ,!» :ыв [oss of lht
capillaries, marked aneurysmal dilalion of the terminal
capillar)' network, and relatively little fluorescein leakage
from the affected capillary bed are features lhal differen­
6.49 Btfaferal, idiopathic, juxtafoveolar, relinal
capillary occlusion and telangiectasis, group iA,
Л - С This 5-9-ye-ar-plcl wom an com pl,iined of onsel of a posi­
tive scolom a of I by rij^hl eye lhal herein b Vveaks previously
bul Pti.irreased in size 1 w eek previously after taking predni­
sone CiQm^ daily tor 2 weeks. She? had a past Hmbry of iritis
in the left eye and recurrenl ulcerative colrLis. Visual acuity
in lhe right eye was 24У200 and in the left eye, JO/JO. S o le
the inegular ischem ic whitening of the retina in lh e central
m acular area of the right (A}: There was no evidence of
iridocyclilis. Angicnbaphy revealed evidence of relinal ca p ­
illary arteriolar and occlusion and irregular dilalion of Lhe
paracenlral relinal arlerioles ill and Cj. N in e years iaLer she
had e vid e m e of posterior synechia and an immalure cala-
racL in Lhe ri^hl eye. The visual fund ion was unchanged.
There was [ocaI dilaLion of Lhe retinal capillaries adjacenl 1o
Lhe enlarged capillarv-free zone centrally. The lefl eye Was
ПОТГПйЗ.

tiate ihese patients from those in groups I and 2. In one !.?--£■: AtcpU Ired perifoveolar retinal le3angiecCasds and cap il­
famiEy lhe retinal telangieclasis was associated with fron­ lary occlusion in a middle-aged woman w ilh polycyl hernia
vera. Despite Earye areas of capillary non perfusion centrally
toparietal-lobe pseudolumors, comprised of s-mall blood
in hoLh eyes, hervisu-.il acuilv was 2(1/25.
vessel damage and fibrinoid necrosis of while matter in
UilaLeral. idiopnlhk j uxlafoveola ( rcHin.nl capillary pctlu-
the absence of evidence of vasculitis.v'" Van hffenlcrre et sion and lelangieclasis associaled With central nervous sys­
al. described three sisters wilh similar retinal findings tem in volvem ent group 3L3.
involving retinal telangieclasis and capillary occlusion in G —|: A 47-year-old man had a 1-year history of progressive
the peripheral retina and posterior pole, associated with Loss ol vision in both eyes. Note lhe slight Lemporal pallor
poikiloderma, graying of the hair, and idiopathic non ar­ ot bolh optic discs, focal obliteration of lhe capillaries in Lhe
teriosclerotic cerebral calcifications.l,lU Pathology stud­ cenlral m acular region, and aneurysmal dilalion of some
ot" the terminal capillaries (G and H^. Angiography showed
ies revealed smal [-vessel hyalinosis caused by baseinenL
irregular w idening o f Lhe capillarv-lree zone, aneurysmal
membrane thickening involving the digestive (ract, kidney, dilation of the abnormal blood vessels, and no evidence of
and calcified areas in the brain. In another family wilh evi­ dye leakage (I and |J.
dence of autosomal-dominant inheritance of both central К and L: This 51-year-old man w ilh a poorly defined neuro­
and peripheral retinal obi iterative vasculopathyr there was logic disease developed progressive loss of Central vision in
associated Raynaud's phenomena and menial changes, bolh eyes. His visual acuily was 2Q'70 in the TighL eye anti
mainly forgetfulness, aggression, and depression.1"'1 20/30 in Lhe left eye. The macular changes and angiographic
findings w ere identical Lo those o f the palienl depicted En G —J.
Fh!ers and Jiendfcn reported similar macular lesions in
three family members of two successive generations. These
patients did not have optic atrophy or neurologic disease. phenomenon may be associated in some. Other organs
somethnes involved include the Eiver with elevated
C E R E B R O R E T IN A L V A S O JL O F A T H Y enzymes, kidney, and osteonecrosis of the blip."1' '' 'J lliree
disorders that appear to be related lo each olher and share
Cerebroretinal vasculopathy is a rare adult-onsel [fourth
the same genetic locus at 3p21.1-p21.3 are: (1) hereditary
decade onwards) autosomal-dominant disorder involv­
vascular retinopathy; (2 ) cerebrorelinal vasculopathyr and
ing the microvessels of Lhe brain and retina due to fra me­
(3) hereditary endotheliopathy with relinopathy, nephrop­
sh ifl mutations in the gene TREXI .<l0:| Patients present
athy, and stroke.|,]J C
'SJ
with vision loss, seizures, hetniparesis, apraxia. dysarthria,
or memory loss. Progression to blindness, a neurovegeta-
Live stale, and death ensues within 5-10 years. It was first H ER ED IT A R Y H E M O R R H A G IC
described by Grand el al. in TO family members and sus­ T E L A N G IE C T A S IA (R EN D U - O SLER -
pected in eight others, spanning over four generations.^'1 W E B E R D IS E A S E )
Retinal capitlary and smal L-vessel о bliteral ion and tel­
angiectasia involving the macula alone, or including the Hemorrhagic hereditary lelangiectasia is a dominantly
periphery, are seeni?®5-1"06 Retinal or optic disc neovascular­ inherited disorder characterized by lelangiectasias of the
ization occurs occasionally.^' capillaries and venules involving many organ systems,
Pseudotumor of the brain due to fibrinoid necro­ including the skin and mucous membranes and visceral
sis from ischemia can mimic a tumor in approximately AVM& The affected blood vessels are friable and prone lo
half of patients, while the other half may have multiple bleeding. The most frequent signs and symptoms include
small white-mat ter lesions, which may be misdiagnosed epistaxis, gastrointestinal trad bleeding, and dyspnea
as demyelinating disease. ,U"-(,|U Migraine and Raynaud's on exertion caused by either hemorrhage or shunting
. V '.
of blood through abnormal vessels in the nasal mucosa,
gastrointestinal tract, liver, brain, and lung. Paradoxical
einboli/ation and stroke may occur when venous thrombi
from the lower extremities and pelvia pass through AVMa
in die lung and lodge in the brain.
Multiple spiderlike telangiectases involving the palpe­
bral conjunctiva occur frequently and may cause bloody
Leaning. Involvement. of the retinal blood vessels occurs
tn frequently. ;,u-"|:: Brant and cowo rkers-1,1: examined 20
patients w ilh heredilarv hemorrhagic telangiectasia and
found relirtal telangiectasis in two patients.1'1’ In their
review of the literature they cited reports of four patients
with retinal vascular malformations, primarily AV.Ms., in
association with hereditary hemorrhagic telangiectasia.
Ceisthoff and covvorkers examined 75 patients, of whom
none had retinal telangiectasia,. but 28 had conjunctival
telangiectases.11' Intraoperative choroidal hemorrhage
has been reported in each eye of a -year-old Caucasian
woman- one during vitrectomy and the other during
phacoemulsification,^'" and large choroidal vessels visible
on fluorescein and indocyanine green angiography in a
73-year-old wilh serous RPE detach mentis*21
t ..1 E) Id Ibpa Ihic retina I Vasculitis^ neurysms, a nd
neuroretinopathy^
A—L: This palient presented w ilh sevKirtil hard exudiilus in the
pusLerior pole л ssiOL iated vw-i IК лпеш уытм ! dilations ut the
blood vessels on opCiu d ist anti in (be simo-undint; area iA
rind B:. Fluorescein лпцшдмгг, the mull ipie aneu­
rysms nlon^ 1he riHinal arterioles (C and El'. A mid peripheral
angiogram showed |jeripher.nl nunperfusion 16(У in bolh
eyes {& - C ). Thu- f]LHient u r i k i W ^ p d m itira l pholocoa^ula-
tiun in Eit)lh eyes. The апиитучиз worsened ovur time [H j and
he also developed flat N V E in Hie left eye. Ttiere was pro-
gSfcsive ^leathing and occlusion of Lhe retinal vessels and
further N V t in i» t h еутея !I—L i over I be ne*r year.
|{ iu u rB L ^y и Г U r. N ic h .ir d S p ^ iiJ u .)
Two types of hereditary hemorrhagic telangiectasia.
H r f t l [more frequent pulmonary and cerebral AV.WsJ,
from mutation in the endoglin gene [£MCJ) and ННТ-Й
(more frequent hepatic AVVls) from mutation in activin
receptor-1ike kinase 1 gene {A C VJU J, A ltf J, chromosome
] 2q ] 3] are knoWn^ 2621
ID IO P A T H IC R ET IN A L
V A S C U L IT IS , A N E U R Y S M S , A N D
N E U R O R E T JN O P A T H Y : BILA T ER A L
N E U R O R E T IN O P A T H Y W IT H
M U L T IP L E R ET IN A L A R T ER IA L
A N EU RYSM S
Multiple, peculiar, saccular, and fusiform aneurysms
InVbivldg all of lhe major relinal arteries in both eyes may
be accompanied by neurorelinopatby, vitreous and ante­
rior-chamber inflammatory cell infiltration, and angio­
graphic evidence of arterilis in children and young adults
[Enures 6,50 and 6.5l).!'~,|"rtSl> 'ihe multiple aneurysms
protruding from both sides of the retinal arteries, as well
as lhe V-shaped aneurysms affecting lhe arterial bifurca­
tions. give the impression of a series of knols in the arte­
rial tree [Figures 6.50 and 6.51). Ih ey may extend from
the optic nerve head into the midperiphery of lhe fundus
and may be associated wilh irregular dilation of the retinal
wins, vascular sheathing, focal areas of capillary telangiec-
Lasis, retinal hemorrhages, peripheral zones of occlusion
of lhe relinal circulation, retinal neovascularization, and
vitreous hemorrhage. Swelling of the oplic nerve head
may be accompanied by retinal exudation, juxtapapillary
retinal detachment and a macular slar (Figures 6.50 and
(L S I ).1*24 l-'luorescein angiography may demonstrate dye
leakage from some of the arterial aneurysms, focal peri­
venous staining, optic nerve head slaining, focal areas of
retinal capillary staining, peripheral zones of capillary7
nonperfusion [Ngures 6.50 and {j.51}, and ret in,si neovas­
cularization. Development of these arterial aneurysms over
a 3-year period has been observed in a young woman who
presented initially wilh symptoms related lo peripheral
b.5 E Multiple retinal and optic nerve head arterial
aneurysms, arlerrtis., and neuroretinitis flRVAN}.
A —F: A 21 -yoar-ol d wom-ian com plained of progressive lass of
cunlral vision in both l"yes. N o le lhe marked tortuohilY and
irregular di Ial ion ot" lhe rTiaj'o| opLic nerve head and relinal
arteries that ex kind into Lhe peripheral fundus [А, B. and D.
and the circin ale paLLem ol lipid-rich exudate surrounding
Lhe opLic disc in both eyes. There was peripheral capillary
Leianj^iedasis in areas posterior Lo zones of retinal Vascular
ohlileralion ■□:. Angiography denionsirated lorluosily, irregu­
lar caliber, aneurvsm lormalion, and total ureas of slaining
o f the major arteries, ol Ih e optic disc and relina IE and FI.
G —J: Л 7-year-old fem ale w h o Was healthy co m plained of
blurred spot in Ihe right eye. She saw 20/20 in l>oth eyes.
Fundus examination revealed In e w y s m s in Lhe arterioles
coming olT Ihe disc wiLh large areas of hard exudates in holh
eyes. Huorescein angiogram showed aneurysmal difalions
ot" Lhe retinal arlery in and л round Lhe disc. Her peripheral
ru1ir:a was perfused normally.
| {j- l, а ш г к ' . у u f [ J t. U tiv irn i.b t i ]
retinal neovascularization.6^ Ll is uncertain whether the
arterial aneurysms and Lhe other retinal vascular altera­
tions are caused by a congenital retinal arterial defect or
are the product of an acquired inflammatory allergic vas­
cular disease.. If the lalLer is true, then these palients LTtay
have some pathogenetic relationship to those with Falesr
disease. 'Lhe value of anti-inflammatory medications
including steroids and immunosuppressives and photo­
coagulation in the manage men I of exudative complica­
tions is uncertain but should be tried in appropriate cases.
Pametinal photocoagulalion (PR P) is required for those
eyes wilh extensive retinal nonperfusion and new-vessel
formation [E'igure 6.50).
D IA B E T IC R E T IN O P A T H Y
Diabetes mellilus is a heterogeneous disorder c f carbo­
hydrate metaboltsm wilh multiple ettologic facto rs I hat
ultimately lead to hyperglycemia. I'here are two primary
types of diabeies. ]ype 1 insulin-dependent diabeies mel-
Eitus (ID D M ) is an autoimmune disease characterized by
hyperglycemia resulting from loss of the pancreatic islet
cells. Up to 90% of these patients and 5.1% of their non­
diabetic relatives have demonstrable serum tilers of islet
cell antibodies/'4 lhe age of onset is before 30 years and
often The disease begins in childhood. riype 2 noninsulin-
dependenl diabeies (N1DDM) is characterized by late-
onsel hyperglycemia typically occurring in obese patients
who are ofLen asymptomatic at the time of diagnosis.'13'
It appears to result from deficiency in the regulation of
insulin secretion and/or in its actEoti at the cellular level
in the liver and peripheral tissues. Secondary types of dia­
betes may be associated with pancreatic disease, excess
counterinsulin hormonal disorders, and drug-induced and
geslational diabeies. In ail types, hypergjycemia, although
of primary' importance, is only one of many pathogenetic
factors (aldose reductase-mediated cell damage; vaso-
prollferative factors produced by hypoxic retina; growth
hormone and erythrocyte, platelel, and bEood viscosity
abnormaEilies) involved in this complex metabolic disor­
der affecting all of Lhe major organ systems, including the
eye/ "1 '61l' Although there has been much emphasis on the
importance of the alterations of (he blood vessels in regard
to the morbidity associated with diabeies, primary meta­
bolic damage to the parenchymal cells is impor Iant.1:1 ' 'L'hese early anatomic and physiologic changes are respon­
Bor example, the development of color vision abnormali­
ties (acquired blue-yellow defect}, abnormalities in con­
trast sensitivity, and electro re Linographic alterations in
some diabetics may precede any demonstrable evidence of
retinal vascular abnormalities."
India ink injection techniques, trypsin digestion prepa­
rations. and fluorescein angiography have been important
in elucidating the anatomic and physiologic changes that
constitute diabetic retinopathy."1'"'1" 'I'he initial changes
involve the retinal capillary bed and include selective loss
of pericytes., microaneurysm formation, thickening of the
basement membrane, focaE closure of the capillary bed.,
dilation of adjacent capillaries, shunt formation, and per­
meability alterations (figure (S.52)."" Jhese changes
may be followed by arteriolar closure, large zones of vas­
cular nonperfusion, and proliferative neovascutar changes
within and on the inner retinal surface. " ' Microaneurysms
develop as outpouchitigs that initially involve primar­
ily the prevenular capillaries al sites of loss of pericytes
(perilhelial cells}. Jhey may arise as an isolated change
or may be clustered around focal zones of capillary occlu­
sion. I heir walls may be thin by weakening or thickened
by proliferation of the endothelial basement membrane.
Jheir lumen occasionally may be packed with agglutinated
erythrocytes or a thrombus. Focal zones of Loss of capil­
lary endothelial cells, thickening of the capillary basement
6.32 Eiacfcground diabetic retinopathy.
A-F: Иго^пнкгюп cl ifeJmjJajTO 1Ьл1 OCciijred between
Septemher 1985 |Д| and January 19S7 <С-Ё). Argon laser
traaLmenl w a s given. In January 199T, visual acuiLy was
20/25 and Ihere was minimal evid en ce o f relinopathy (F).
G —n Ischem ic background reHnnpaUiffi in an irrsulm-depen-
rienl dialietic with prominent cystoid macula^edeftia, dilated
peripheral m acular retinal capillaries, and evidence of lass of
Lhe juxlafoveolar capillary network (stereo photos G and Hi.
An^icjjjrnphv I) shew ed loss o i pericentral ca p iI'Eary network,
and capillary полрегг'имст In lhe area o f Lhe cottcm-wcjol
patch and in lh e lempnrnl periphery af Иъе Ш аси Ш
|—L: Submaculnr hemorrhage Ijl cause by bleeding from ju?i-
Lafoveolar fnicravascu lar changes 'K i cleared spuntaneousfy
(U and the patient recovered 2lV3() visual acuity.
membrane, and reduction of blood flow develop and are
associated with surrounding areas of compensatory capil­
lary' dilation, capillary endothelial proliferation, and per­
meability alterations, Ihis change in permeability of the
dilated capillaries and microaneurysms is associated wilh
extravasation of serous and lipoprotein aceous exudate
and, in some cases, intrarelinal bleeding [figure 6.52|).
Other physiologic changes accompanying diabetic reti­
nopathy include alterations of blood How and blood VJs-
m slty^ S-fi,Sft Autoregulation causes venous dilution when
local tissue hypoxia and hypoglycemia are detected. With
constant changes in the vessel caliber from fluctuating tis­
sue glucose levels, the venous lone is eventually lost, result­
ing in chronic venous dilation. ] lyperglycemta per se can
cause dysfunction of autoregulation.
sible for the ophthalmoscopic changes referred to as back­
ground and nonproliferative diabetic retinopathy 'ihese
include red dot like microaneurysms*, areas of dilated relinal
capillaries, superficial flame-shaped or deeper dot and blol
relinal hemorrhages, white-centered hemorrhages, yellow
exudates, and focal areas of gray-whitening of the retina (col-
lon-wool spots] (figure 6.52 J/"1'1'-" '-^'Microaneurysms are
lhe earliest clinical sign of diahetie retinopathy (E'igure 6.S2
Л). 'Ihey may occur anywhere in the retina. In some cases
they are widely distributed, whereas in others they may he
concentrated in the central maculararea.
Visual loss in patients with nonproliferative diabetic reti­
nopathy occurs primarily as iht? result of macular exudation,
particularly in patients with late-onset diabetes (I i.gure 6.!>2
-|hj5 т л у occur either as the result of focal
leakage of exudate from one or more dusters of microan­
eurysms and dilated capillaries, each often surrounded by a
ring of yellow, deep relinal exudates, or as the result of dif­
fuse Leakage from most of the retinal vasculature in the mac­
ular area. In general, the loss of central vision parallels Lhe
degree of intrarelinal exudalion seen biomicroscopically and
angiographically. Minimal loss о faculty may be associated
wilh mild intraretinal exudation from capillary microaneu­
rysms lhat are eilher confined Lo the posterior pole or are
more widely scattered. More pronounced degrees of intra-
relinal exudation are often associated with greater evidence
of dilation of both the small and bige retinal blood ves­
sels. Scattered yellow елиdates, relink hemorrhages, and
occasional cotton-wool spots may be present. Cotton-wool
spots In diabetic retinopathy are indicative of focal zbjbSS of
relative retinal ischemia caused by either partial or, in some
cases, complete closure of the capillary bed in the zone of
retinal whitening [Hgure 6.53)JK£№72'- Ihey occur com­
monly during the early development of nonproliferative
diabetic retinopathy are not necessarily related to elevated
blood pressure, and do not necessarily suggest a high risk
of progression of Lbe retinopathy. In general they persist for
a longer period of time in diabetes than in hypenension.
When they resolve, they may be associated with a local sco­
toma.. nerve fiber bundle scotoma, or no scotoma/" 1 lhe
presence of numerous cotton-wool spots, particularly when
associated with other signs of pceproliferativie retinopathy,
may indicate rapidly progressing retinopathy.
A frequent clinical picture seen in patients with early
loss of vision is that of one or more circinate zones of yel­
low lipid-rich exudation, usually centered in the paramac­
ular area and extending into the fovea (blgures and
C, and 6.53D). the yellowish deposits surround clusters
of microaneuiy&ms and cloudy intra retinal and sub retinal
exudate. Circinate zones may be round, oval, or irregular.
They are most frequently centered in the temporal portion
of the macula, lhe amount of lipid exudation around the
retinal capillary abnormalities in these patients is related
to their serum lipid levels and their diastolic blood pres­
sure. Lhe presence of extensive deposits of intraretinal
lipid exudates may be indicative of hyperlipidemia (see
hgure 6.fiSj-L ).fi?5 (See discussion of hyperlipemic reti­
nopathy, p. 6Ю.) Transudation of serum lipids into the
vitreous in such patients may occasionally simulate
endophthalmitis.11'4’
Some patients wiLb diffuse retinal capillary leakage
and C M t angiographically may show minimal evidence
of yellow exudate and loss of retinal transparency biomi-
bfQscoplcaJly^3^' l'"> lhe edema may wax and wane,
remain stationary for long periods, or steadily progress.
Occasionally the C M E may occur in the absence of promi­
nent background retinopathy and dilation of the major
retina] vessels.1'6^6^ Other causes of central vision loss in
diabetic patients include hemorrhage from lEte perifoveal
capillary abnormalities {]:igure 6.52), peri foveolar capil-
Eaiy occlusion [figure &.S2 )r vitreofoveal traction (Figure
7.09] and J), and epiretinal membrane formation.
When the vascular occlusive phenomenon caused by
diabetes begins to Involve the precapillary arterioles and
larger retinal arterioles, fundus changes characteristic of
prep rot ifera Live retinopathy develop. These include mul­
tiple colton-wool spots and retinal hemorrhages, dark blot
hemorrhages, venous beading and loops, irregular dilated
segments of the capillary bed [intraretinal microvascular
abnormalities, or IRMA], and large areas of loss of reti­
naE vascular details or "featureless" retina (J:igur« 6.52G
and 6.54A-B). I'hese latter areas show extensive vascular
nonperfusion angiographically [Figure 6.54). Ihis process
6.53 Diabetic exudative maculopathy and response to
treatment.
Л a n d B : O r t i t i a J e lip id associate d w ith fo v e a I lh k k e n in g
in I his pa I к 'п I w h o ii.ss h a d p a n ie tin a l p h o jfa c m g u ta tia n for
p ro life ra tiv e d la b e lic F-elinop a lhy I.A.I. F o u r m o n th s later a lo t
ol lht> lip id e x u d a tte h a v e clis a p p e a re d IK-'i.
C - F : N o n p ro life r a tiv e d ia b e tic re tin o p a th y a n d c irc in a te
m s tliE o p a lh y b e fo re IС a n d t?i a n d afapr IF nirgcm laser p iio -
to c o a g u la liio n . N o t e fe s o lu lio n o f the lip id o x и d a le :F-l.
G a n d H : H is to p a th o lo y y o f d ia b e tic e x u d a tiv e m a c u Eo p a th y.
N o l o lh e m a c ro p h a g e s la rta w s ) e n g u lfin g Lhe lip id e x u d a te
a n d jSfridence o f cystic d e ffin tr a liiH i o f Lhe retina C j .
Diabetic neuroretinopaihy fpapillopalhy).
I—I L This yqu-ng svorijt^h W ith c h ild b tx jd d ia b e te s n o te d Lbe
s u d d e n unsel o f vis u a l lo s t in Lhe righl e y e . N o t e th e m a c u la r
slar, the o p tic d in t s w e llin g , a n d m in im a l u vid enc e o f b a c k ­
g ro u n d d ia b e tic re tin o p a th y {I a n d J!'. Six m o n th s later h e r
visual a c u ity h a d i m p r o w d lo 2tVJ20. N o t e Ib o p a llo r o f the
o p tic d is c I.Kj. T h r e e m o n th s later she e x p e rie n c e d lb e sam e
s e q u e n c e o f e ve n ts in the left e y e .
D L D M O A D (WoEfram syndrome}.
L: K i g h L p a le o p Lic d is c t le fL , n o t s h o w n I of a n 1 f!-y e a r-o ld
w ith ty p e 1 d ia b e t e s , n E p h r o g e n ic d ia b e t e s rn s ip td u s , b ila t ­
eral p ro g r e s s iv e o p tic a t f p o m a n d d e a f n e s s . H o a ls o h a d
h y d r o n e p h r o s is s e c o n d a r y t o the d i a b e t e s i n s i p i d u s a n d r e n a l
I n s u f f i c i e n c y . t i e n e L e s t ln g f o r b V F S ? ц е п е w a s p o s i t i v e .
I I -It, Ггот Li.irr c;l al i ■ I ЧДО). Апм-til ;ir, ,\кчЕи a I A iH jd .itiu ti. A lj
rif^nlb raM.'-rvLHJ. t>-J, AImj. V,in n u zii, LnSnfivM I., Ih^ до№ы1 A il.is,
S.iui>Lk’ r-. iU K ). 47fl-4J-70GH-iJ2n-1r [5.2ДМ
of vascular occlusion frequently involves the peripheral
retina and in some cases may initially be largely confined
lo the ext гаmacutar areas, in other cases capillary nonper­
fusion affects the central macular area early and may cause
loss of visual acuity.’’7<
>The IRM A occur near areas of vas­
cular nonperfusion and in some cases represent dilated
segments of the capillary bed or shunt vessels, whereas in
other cases lh.ev are intraretinal newly developed blood
vessels.^
Lbe risk of developing proliferative diabetic retinopa­
thy (PD R) is approximately 50% within 15 months in eyes
wilh preproliferative diabetic retinopathy/'*1 It is impor­
tant lo realise that, by the time neovascularization has
commenced, many of lhe signs of active preproliferative
retinopathy may no longer bepreseLtl. Neovascularization
usually begms within 45* of the optic disc and oflen arises
oti the optic disc. New vessels are subdivided On the basis
of their location as follows: those arising on or within \
disc diameter of the op Lie disc (NVL>), and those elsewhere
in (he fundus [NViiJ. 'lhe NVD begins as tine loops or net­
works of vessels lying on the surface of the optic disc or
bridging across the physiologic cup. They may be difficult
lo differentiate from dilated optic nerve vessels. Likewise,
differentiating NVli front IRMA may also be difficult, par­
ticularly when the N VE do not yel show any of (heir char­
acteristic features, including wheel-like network, extension
across both arterial and venous branches of the underly­
ing retinal vascular network and accompanying fibrous
iJ ir iK 'f r r Rctinopnifn/ 5 -4^
proliferation. fluorescein angiography is helpful in dis­
tinguishing new vessels, which leak difTuseEyr from ves­
sels located within the oplic disc and retina, which show
minimal leakage New vessels typically form networks
simulating sea fans (figure 6.55A-C), but, in some cases,
particularly when ihey arise from the optic disc, they may
grow across lhe retinal surface and present the appearance
of mature retinal blood vessels (E'igure 6.55E'-ll]. Patients
with new vessels are often asymptomatic until vitreous
separation elevates the new vessels and causes intravitreal
bleeding. Vitreous separation often begins along the supe-
rotemporal vessels, tempi) гаI to the macula, and above or
below the opLk diM' ■ I'lu1 vUronis usually does n< l
separate from Lhe disc in palients wilh N VD. 'i'raction on
Lhe new vessels by the partly separated vitreous may cause
vitreous hemorrhage. Bleeding into Lhe vitreous may also
be caused by avulsion of retinal blood vessels [usually a
vein) or a relinal tear. Displacement and distortion of
Lhe macuEa caused by vilreoretinal traction and epiretinal
membrane contraction and tractional detachmenl of the
macula may cause loss of visual acuity, dimness of vision,
metamorphopsia, and d ljftc n tfa ^ ^ '* 8' Focal serous
detachment of Lhe macula is an infrequent complication
of diabetic retinopathy unless it occurs secondary Lo vit­
reous traction wilh or without macular hole formation
(ftgure 7.03f-E1J.
A peculiar form of occult vitreomacular traction occur­
ring in patients, particularly after unsuccessful scalier
macular pholocoaguialitm, may be responsible for severe
macular edema and diffuse fluorescein staining of lhe
maoila. Visual function in Lhese latter patienls may
improve dramatically following pars plana vitrectomy
(see figures 7.05G and I L, and 7.031 -K) Nasrallah el al.
found Lhat adult-onset diabetic eyes wiLh macular edema
were less likely to have posterior vilreous detachment than
eyes without e d e m a Ihey found the reverse was Lrue in
Eyes of patients wilh type 1 diabetes.'
PDR. may occur in lhe peri macular area [figure 6.55)
but it infrequently occurs near the center of the macula/''"
W hat may be an aborted form of intraretinal and p re reti­
nal neovascularization may give rise to a peculiar cluster
of coiled aneurysmal blood vessels in the juxtafoveolar
area, particularly in insulin-dependent diabetics wilh evi­
dence of macular capillary non perfusion and following
PRP (figure Thest juxtafoveolar aneurysmal
changes are associated with excellent visual acuity and
good visual prognosis and may occur in both eyes. Similar
abortive nodular neovascular outgrowths without an extra-
vascular fibrous component may arise along the major
vascular arcades in eyes with extensive areas of capillary
nonperfusion (figure 6.53А-С).й*'1 Histopathologically,
they are nodules of vessels with gross hyalinidation of
their walls and without a fibrous component.1'L rihese
Eesions may represent aborted forms of neovascularization
[hat develop in the absence of a vilreous scaffold.
'Ihere are significant differences in the natural courses
of 3D DM and N lD D M J6M,taj Jn chiidbood-onsel
fe.^4 Accelerated pro Iiterative diabetic retinopathy.
A—K: This 18-yea r-oid African Am erican yirl w ith type 1 dia­
betes had vary minimal N V D in I he rijjhl eye and no new
vessels in Ih e (eft eye. Her retinal veins w ere dilated and
she had several intraretinal m icrovascular abnormalities
(IffifvtA in bolh eyes ■arro w s in addilinn U> scattered colton-
Vuftol spots 'A i-iп-cl Angiogram confrrniLKl extensive c.apil-
lary unnperfusion and lh e presence of widespread IK.VlA in
bciSh cyos. .Vlontaye images of Ihe riijhl and left eye sbaW
estensive ischemia. Е-1ет renal function was ^brrewmal and
□lopd iuijArs w ere in Lhe (jOOSmg/di. In spite of рлпгеНпл!
pholocoagulation bef^un in both eyes voon afler these pic­
tures, she developed biEaLeral extensive capillary drop-oul
and new у Pise I Д (F, C. L, and )J- Fhe let"1 eye si ill had some
perfusion of her native vetsels w hile lhe ri^hl o nly showed
dye in Ihe residual vessels on Lhe disc (H). Further panreLf-
naE pholocoa^Lihttion did nol pnsvcml nuovasc ular glaucoma
LfiiiL developed in bcuh с у й ret|-uirin^ brlatefal Luiw shunls
(K). Com plicated cataracts developed quickly w ilh new ves­
sels on the anterior surface of the lens :K. and vision dropped
Lo no li^hL pencepLion, followed by tradlkinal relinal delacb-
ment confirmed on uLtrasoond. She died w ithin a year o f her
inilial evaluation.
type 1 diabeles, retinal microaneurysms and other dia­
betic retinopathy seldom develop before puberty.0'-1"" u0
In a popula Lion-based study of 271 insulin-dependent
patienls diagnosed before 30 vean of age and without
retinopathy at Lhe time of initial examinalion, 5У% of
patients developed retinopathy, including 11% with pro­
life rative relinopalhy, by the Lime they were examined 4
years later }l Overall worsening of Letinopalhy occurred
in 41% of the population, whereas improvement occurred
in only 7%. 'Ihe incidence of proliferative retinopathy
rose with increasing duration until 1.3-14 years of diabe-
les and thereafter remained between 14% and 17%. Klein
and coworkers found tbaL Ш.2% of adult-onset diabetics
have ret inopal hy al the lime of initial diagnosis.ш During
a 4-year period Lhey found Lhal 47% non users of insulin
without retinopathy developed il, that 7 % of those with­
out proliferalive retinopathy developed il, and thaL wors­
ening of the retinopathy occurred in 34% of all of the
patienls.1" for nonusers of insulin the corresponding rates
were 34% for any retinopathy. 2% for developing prolifera­
tive retinopathy, and 25% for worsening retinopalhy In
ihose initially free of retinopathy approximately 50% of
those using insulin and 35% of nonuseis will develop reti­
nopathy wilhin 4 years of diagnosis. ш During this same
period of lime approximately 35% of users and 25% of
nonusers wEH develop worsening of their retinopathy.
'i'he most important risk factor for developing diabetic
retinopathy is duration of the disease "l: '■ ■
■ JSetinopalhy
in LDDM occurs in frequently before 5 years after onsel of
lhe disease, It Is present in 27% of patients with disease
duration of 5-1G years, in 71% wilh longer than 10 years,
and in over 90% afler 30 years, lhe prevalence of back­
ground retinopathy in N ID D M 11-13 years after lhe onsel
is 23%, afler 16 or more years il is 60%. and after I I o:
more years 3 % haw proliferative retinopathy."" Other risk
factors associated with progression of dia belie retinopathy
include number of £iicroaneuiys tfta*70й albuminuria,"'1'
elevation of blood pressure. 0(1 11J posterior vitreous
attachment,61wa4j?L0 increased fovea! thickenmg/ '1 blue
or gray arides. 12 sm oking,"1' IS,7|J increased testosterone
Levels in males willt type ] diabetes. 1 ' previous irradia­
tion lo the eyer,LI: reduction in eEectroretinographic oscil-
Eatory potentials,'1' environm ent! and racial factors/"'
prej;nanc\'. 1,1 and cataract extraction.'' 0' 25 Carotid artery
obstruction may have a favorable effect on diabetic reti­
nopathy in some patients.'16i72B
Kluorescein angiography has provided greal under­
standing of (he microvascular changes caused by diabe-
17.72?- Г31 C |1 ц к и р а 1 Ь Ы ^ -
correlations have helped in interpreting and understand­
ing these lhe develop ment
of mJcroaneiirysms and alterations in Lhe capillary perme­
ability are lhe earliest changes detectable with angiography
Ш the diabetic retina (figure 6.52A). lhe microaneurysms
are predontinantly on the venular side of the capillaiy bed.
Kound and occasionally fusiform microaneurysms are scat­
tered in the macuEa and perimacular region and have no
particular relationship to the distribution of lhe major reti­
nal vessels such as occurs in hypertensive retinopathy, F-'ocal
areas of capillary closun: may develop wilh in the capillary
bed affected by marked aneurysm formation. Capillary
closure occurs much more frequently and to a greater
extent initially in the mid peripheral fundus and generally
increases towards the periphery.e_'4 Some enlargement of
Lhe t'AZ occurs commonly in diabetes but is usually unas-
sodated wilh visual loss until the VAZ approaches ЮООцт
in diameter (E'igure 6.52C-E).1' " " " Capillary closure occurs
less frequently in the macula and rarely if ever, in the area
of the juxtapapiltary radial capillary network^4 ' 1’^ 1'733''3''
Extensive mid peripheral and peripheral capillary closure
may be relatively inapparent ophtbalmoscopically, and its
extent is directly correlated with the development of disc
and relinal neovascularization. Dilated, tortuous, shunt cap­
illaries may traverse large areas of capillary closure that are
oflen more evident in the more peripheral retina. Intensive
microaneurysmal changes in the capillary bed may be dem­
onstrated angiographically in the macular region in patients
who do not have significant loss of visual acuity, lhe per­
meability changes in the capillary bed and the degree of
serous exudation inlo the exlracellular space of lhe retina
are variable and are the most important factors causing
Loss of macular function, in some cases, however, progres­
sive closure of the perifoveal capillary network is the cause
of loss of macular function (figures &.52C-], f i d 6.54A-]),
ihis closure occurs more commonly in pa lien Ls With
puveni Ie-onset d i a b e t e s / Ihere is no iluorescein
angiographic evidence of choroidal vascular disease lo
account for the loss of central vision in diabeies. ihere is
some indoeyanine green angiographic, histopathologic,
and scanning electron microscopic evidence that the cho­
roidal vessels may be affected in diabetes."' "' Areas of
t..j -I Continued
L and M: This pa tier L with proliferative diabetic retinopathy
,ind suiihyaloid hemorrhage underwent p arrruliпаI pholooo-
ajjubtion iL , Fallowing which he developed contraction of
the posterior hyaloid and traction thickening of lh e under­
lying retina lM:.
\ and G : This- youn^ palk^rl sou^hl tneatmenl because
ot vitreous hemorrhage in lhe li^ht eye. She had extensive
neovascularization of lhe opLic discs and periphery of both
&bs- "I here WHi 4nJiOftraf)hlc evidence of extensive cap il­
lary rionpiylu&iori in rhe mid peripheral and peripheral fundi.
Fanrelinal pholocoa^ulation in lhe right eye (N) resulted in
Ыонипе ot" lhe optic disc new vessels EjltL incom plelt1 t lohuie
ot lhe retira! n ew vesiels ■iarmw. Oj.
neovasmlar proliferation on the surface of the retina are
always accompanied by angiographic evidence of dye leak­
age from these vessels (Figure; 6.55J.
l he pathogenesis of diabetic retinopathy is complicated,
controversial, and beyond the scope of this book. Jhere is
overwhelming evidence that hyperglycemia is important in
(he pathogenesis of retinopathy but genetic and other fac­
tors are importanL63i ^ M £3 Release of angiogenic factors
(VEGF) in the hypo perfused hypoxic retina is important in
th e de vel op menl of pro! iferat ive reti no pa Lhy."16-61 ?i-
l’holocoagulation treatmenthas been advo­
cated for Lreatmenl of exudative and I’DR for many
years.( , ! J i2-7s<> jn recf]1| years randomized
controlled cliiiical trials have established useful guidelines
for use of pholocoagulation and vitrectomy for the treat­
ment of diabetic retinopathy.f,s:j'c,bl-7 ■|,Ll-rr-1 lie fore
publication of the results of the harly Treatment Diabetic
ISelinopalhy itndy (t'EUHW), several randomized clinical
trials reported pbotocoagulation lo be of value in lhe treat­
ment of diabetic macular edema. ,3-7|Л Although employ­
ing somewhat different protocols and case selection, all of
these studies have concluded that laser treatment is effec­
tive in reducing the rate of visual loss in eyes wilh macular
edema but resulLs in significant visual improvement in only
a limited number of cases, 'lhe LTDK5 concluded lhal eyes
wilh mild to moderate nonproliferative diabetic relinopa-
ihy and clinically significant macular edema, when treated
with focal argon blue-green or argon green laser to micro­
aneurysms and a grid treatmerit to zones of diffuse leakage
and non perfusion, show the maximum benefit of treat­
ment (figures fr.!>2L>-J-. and 6.53А-Г)/ "1 Clinically signifi­
cant macular edema was defined as: ( I) retinal thickening
involving, or within 500|.m from, the center of the macula;
( 2 ) hard exudate(s) (wilh thickening of the adjacenl retina)
at or Within 500,1 m from the center of the macula; and [5)
a zone of retinal thickening I disc area or larger in size, any
part of which is wilh in \ disc diameter from the center of
the macula.
Because of the risk involved in treating lesions closer
than 500pm lo the center of lhe macula, it may be prudent
lo follow eyes with dinicafly significant macular edema
showing such lesions when the visual acuity is normal and
i?iViKrfrr Rctjiu^aifn/ 54/
the center of the macula is uninvolved. ihere is little risk
Ёп following s.uch eyes lo delermine whether the edema
is Worsening.™ Oik and coworkers have used a modified
grid pattern technique Гог treating diffuse diabetic macu­
lar edema, emphasizing treatment of diffuse leakage rather
than focal leakage. ' " They have demonstrated (hat
visual acuity and fovea] threshold in these patients aFe pre­
served at the expense of generalised loss of threshold sensi­
tivity across the central Ю п of visual fields '
In eyes wilh mild lo moderate macular edema, ГкГ
should not be used till the macular edema is treated. И1Р
treatment increases lhe risk of loss of visual acuity, par­
ticularly in patients with macular edema. " 1,7711
deduction in the anea of retina needing to be perfused
following PftP redirects more blood flow lo the posterior
pole, ihus increasing the intravascular hydrostatic force
within these vessels, causing increased leakage, treatment
of the macular edema # ith focal and grid treatл tent given
before scatter treatment reduces this risk. f2,7' 1 [f high-risk
characteristics for PDR are also present, dividing lhe scatter
treatment into multiple sessions beginning wilh the nasa!
quad гаms, using a more peripheral pattern of scatter treat­
ment using smaller spot size applications, and using less
intense treatment are techniques that may reduce the risk
of aggravating the macular e d e m a / ^ ^ W J ' ^ f
PI?Г treatment should be carried out promptly in most
eyes wilh PDR lhal have well-established NVD and/or vil-
reous or preretinal hemorrhage. When high-risk charac­
teristics are present, scatter pholocoagulation should be
carried out even in lhe presence of fibrous proliferations
and/or localized traction retinal detachment. Likewise,
scatter treatment is indicated in eyes wilh extensive neo­
vascularization of the anterior-chamber angle, or in eyes
with preproliferative retinopathy and evidence of rapidly
progressive closure of the retinal capillary, whether or not
high-risk characteristics aie presen I (Figure 6.54Л-1}-'"'
lliese latter paLients should be warned of the high risk of
further loss of central vision caused by occlusion of the
remaining vessels supplying the macula.
The prognosis for recovery of central vision Is poor in
pa lien Is wilh angiographic evidence of loss of the perifo-
veal capillary network: severe C M E , particularly when asso­
ciated with significant background retinopathy; organized
yellow enudate in Lhe macula; and severe renal disease and
hypertension. Retrealment of eyes that fail to show an ini­
tial response to scalier treatment is indicated and is suc­
cessful in approximately 5C№& of cases,li6i'?7J,7eij7ft2 'Jliose
who fail after retrealmenl h ave an unfavorable prognosis.
'lhe wave length of laser light used for the Irealmenl of
the various stages of diabelic relinopathy appears to be
relatively unimportant. i>:" Although all of the clini­
cal trials have used fluorescein angiography as part of the
invesligation of patients wilh diabetic exudative macu-
Lopalhy, lhe decision as to whether lo treat, and where to
treatr depends primarily on biomicroscopic observations.
It) г that reason some have suggested that pret real men l
angiography is unnecessary.'
fe.5 I1rol ife rat ive d ia be lit retin opalhy.
A—С : Relinal venous loop 1arrow, A> and retinal
F iE f iv a s c L lla r i n a t io n .
D - H : Severe! pw lilefjttive retinopathy in Lhe righL eye a l
a y(Ji>ng diabetic patient ;ID-F). Scrte lhe Hubhyalnid hem­
orrhage :Ei and lhe prominent nonelev^ted neovascular
Irunks r.idialing frum a masai relinal vein (arrows;, h-H:.
Angiography showed sluggish blood flow w ithin the new
vessel nelwork (G and H).
I: HiblopaLhologv of diabelic proliferative relinopathy (arrow­
h ead s and dilaled intrarelinal blood vessel (arrtswj.
|-L: R in ^u J preretinal fibrovascju lar tissue surrounding the mac­
ula in a patient w ilh severe proliferative diabelic relinopathy.
'lhe favorable effect of pholocoagulation treatment
on diabelic retinopathy is mullifaclorial. Hypotheses to
explain how pholocoagulation causes resolution of the
neovoscular and exudative complications of diabelic reti­
nopathy include reduction of YEG F lewis, improvement
of the blood-ouleF relinal barrier by pholocoagulation
debridement of sick or fatigued RPE cells; release by pho-
locoagulalioti-damaged RPL cells of a factor that reduces
retinal capillary endothelial proliferation and causes res­
toration of the integrity of the blood-inner relinal bar­
rier' 1 " and increased oxygen tension at the inner relina]
surface caused by partial pholocoagulation destruction of
the retinal receptor cells and Rl]li cells.' ' 'lhe increased
oxygen lension occurs in spile of the partial loss of the cho-
riocapillaris that accompanies PRP. ]jong-lerm follow-up
sludies after panpbolocoagulalion have demonstrated per­
sistence of the irealmenl effect for as long as ] 5 yeans.' ' **
Complications of laser pholocoagulation treatment of
diabelic relinopalhy include development of sub retinal
neovascularization,'"' '" subfoveal fibrosis/'110"*0'1 serous
macutar detach in ent,""-"1 ciliochoroidal detach me nL, and
enlargement of pholocoagulation scars.f,)'1
'i'ransscleral ciyotherapy is a useful adjunct lo pholocoagu­
lation treatment when recurrent vitreous hemorrhage occurs
without visible new vessels posteriorly. It is likely small
pew vessels are present very anteriorly; these can be easily
destroyed by two or more rows of transconjunctival periph­
eral стуоросу.^1 w" 'litis is also especially useful in those eyes
that show recurrent vitreous hemorrhages after pars plana vit­
rectomy where no new vessels can be found. Applying two to
three spots lo lhe sclerostomy sites helps in those eyes where
a vessel may be bridging the sclerostomy site on the inside.
Pars plana vitrectomy has beet)me the standard treat­
ment for serious visual loss caused by dense. noncJearing
vitreous hemorrhage; traction retina! detachment; and mac­
ular heterotopia.673,6ftS,76l7fii7M,795,iQ!>-ei!i Eariy vitrectomy
is beneficial in patients with type 1 diabetes and recent
severe diabetic vitreous hemorrhage reducing visual acu­
ity lo 5/200 or less for at least 1 m onth/1 *-1 ,7 1 4 In older
patients with type 2 diabetes and recent severe diabetic reti­
nal hemorrhage, il is neosonable to allow lime for sponta­
neous clearing of the vitreous hemorrhage for 4-6 weeks
before considering vitrectomy. Partial posterior vitreous
i?iViKrfrr RctinL’pnifiw
separation that may follow a vitreous hemorrhage in some b . э f> D i a b e t ic in tra re tin al p го I i fe ra liv e re t Ё п о р а Ih y .
cases may help in en bloc dissection during vitrectomy.
A—C : Peripheral inLrareLinal neovascularization (anowsl.
Karly vitrectomy should be considered as an adjunct lo D and E: This 3fl-year-o!d type 1 diabetic developed several
pholocoagulation in eyes with useful vision and advanced, small inEraierinal b^fcjvaSciJ1ат tTonds in b(]lh Суш 'L?). There
active [nDR with extensive new vessels that fail to show were а few 1ufLs of IJt^Melinffi mit r o v a s c u l a r abnormal ilios
substantial regression after photocoagulalion, or when (arrow 1 EhaE did ntH leak on [he angiogram w hile Lhe N V E
additional photocoagulalion is precluded by vilreous hem­ leaked profusely ■!£).
orrhage and when iris vessels begin to appear.'64 Allhough F— 1 : Focal juxlaloveolar intrareEinal neovascularization w ilh
Mood ;этго№, F'l in а pa lien I with pmiifuTHlive diabetic reLi-
vilrectomy is of value in restoring central vision in patients
nopalhy (F). The preretinal neovascularization seen else­
.who have developed macular detachment secondary to vil­
w here disappeared after pan retinal phoLocoagulation but Lbe
reous traction detachт е ш Л 1"'"'1' it may not be indicated ju>;L;i foveolar in-Lrarelinal neovas^ularizalion Liecame more
when the traction detachment does not extend into the prominttnL (C —If.
manila.""1'1 ' because of the high association of cataracts in I- L: luMafoveal inLrarcVlinal iwovascularizaLion larrowi and
diabetes and their frequent development soon after vitrec­ N V E persisLed (o tte rin g panrelina! p h o lcaw ^ u ialio n in thb
tomy, combined vitrectomy and intraocular Lens insertions 40-year-old type J diabeLic. 5he received further photocoajju-
EaLionr wenL OH to develop LracLion relinal detacbrYUjnl invu Iv­
are frequently done in these patients*1'' Ihe 5-year survival
in^ 1Ii€H macula, and vision dropped o§ 2(V400. F’ars plana
rate of patients undergoing vitrectomy for complications of
vitrertGfHy with lenw val of 1пэ< lion memlwaпе.ъ and lill-ir>
diabetic retinopathy is approximately 75%.'41 p a rre H ra phoLoLoayulaLion restored r vision lo 2LV20 ir>
Pharmacotherapies for diabetic retinopathy include treat­ spile of moderate nonperfusion o(" the pdisteribf pole.
ment of macular edema using intravitreal injection of triam­
cinolone or sustained-release corticosteroids* and to a Lesser
effect intravitreal antiangiogenic agents. '-" и Machemer
first reported the use of intravitreal steroids Lo halt cellular Nonretinal Ocular Changes in Diabetes
proliferation in diabetes., which was not very successful.r 2 C o rn ea
Corticosteroids have ,inLipermeability, antiangiogenic,- and
Diabetics have a higher incidence of dry eyes and
anti fib ro tic effects.1' 1 ihey help stabilize (.he blood -retina!
decreased tear production. In addition, corneal sensitiv­
barrier, down regulate inflammatory factory and increase
ity is decreased. The ability of the corneal epithelium lo
absorption of fluid. Triamcinolone [most recently with­
adhere to lhe basement membrane is altered by impaired
out preservatives) al I and 4 mg can be used in those eyes>
glucose meLabolism. This includes thickening of lhe base­
which fail to, or do not completely, respond Lo focal laser
ment membrane of the corneal epithelium, decreased
phctocoagu]ation.'5j‘l It is also indicated in eyes with C.ME
hemidesmosomai frequency, and decreased penetration of
without significant capillary leakage oli angiography and in
anchoring fibrils. All these contribute Lo frequent corneal
those eyes with diffuse leakage from all vessels in the mac­
erosion and comeat epithelial defects. Jh is is especially
ula. Complications include cataract formation, elevation of
noted after surgery or laseF therapy where the corneal epi­
intraocular pressure, infectious endophthalmitis and acute
thelium can break down easily as a sheet.
toxic/inflammatory response; hence judicious use of intra­
vitreal steroids hearing in mind the potential complications
is recommended, i-’osurdex, a biodegradable copolymer
consisting of 70% dexamcthasone [350 or 700|_:g} and 30% Those patients with significant ischemia, especially of
polylactic-glycolic acid, and IteLisert, a sustained-release lhe peripheral retina, develop neovascularization of the
ешplant of Auocinolone acetonide which linearly releases iris and Eteovascular glaucoma due to diffusion of VLGT
fluocinolone for 3 years, have been tested. (Cataract forma­ into the anterior chamber. Contraction of the new vessels
tion and elevated intraocular pressure are very common fol­ in the iris can cause ectropion uvea and peripheral-angle
lowing these implants and hence haw limited their use. closure, resulting tn neovascutar glaucoma. Recurrent vit­
Antiangiogenic agents bevacizumab and ranibizumah reous hemorrhages can result in ghost cell glaucoma via
have a role for adjunctive treatment of proliferative reti­ blockage of the trabecular meshwork by enlarged macro­
nopathy in eyes Lhat show persistent new vessels in spite of phages that have engulfed blood pigment. Khaki-colored
adequate PRfc in those eyes wilh recurrent vitreous hem­ large cells containing Heinz bodies, which are preci pita Led
orrhage following TEi]> or vitrectomy, preopera Lively lo hemoglobin, are seen in these eyes.
decrease Lhe caliber of large new vessels before parr plana
vitrectomy, and in those eyes with neovascularization of ie n s A bnorm alities
the 1Й5.Й ;И,'И6 By themselves as primary trealment for pro­ Increase and decrease in (he osmolarily of the Lissues sur­
liferative retinopathy they are not beneficial in the long run rounding the lens and the lens itself due to increase and
due to short duration of effect. Jhe ability of an Li-VXCr decrease in the level of the blood sugar cause abnormal
agenls in reducing Lnacular edema alone by altering vas­ focusing resulting in fluctuating vision. Ihe hyperglyce­
cular permeability is limited and variable; response is seen mia per se causes changes in Lhe basement membrane of
only in eyes wilh associated significant retinaL ischemia. the lens epithelium, resulting in posterior subcapsula: and
cortical cataract. Young diabetic patients can develop a
flaky cataract with .superficial vacuoles.
O p tic N erve
Acute opLic disc edema or diabetic papillopathy is a fea­
ture of diabetes. Ibis is unlike ischemic optic neuropathy
and usually occurs in the second lo fourth decades of Life
and generally has no correlation wilh severity of diabetic
retinopathy^'' !l-,D El may be associated wilh only a mild
Loss of vision; often the vision is unchanged. Swelling of
the disc may be accompanied by hemorrhages, exudates, a
star figure, and CME. lhe visual field usually is normal and
may occasionally show some small defects, which include
enlarged blind spot or an arcuate scotoma. fluorescein
angiogram will reveal leakage of dye from die dilated ves­
sels on the optic disc (figure 6.5-E1-K). Jhe condition can
be bilateral in about half the cases. Occasionally the second
eye may be affected Eater. Visual prognosis is usually good
and the papil Iopalhy resolves in a fexv weeks lo months. A
fcvv fv.ik-ii-s arc k'h with mild optic atrophy, lhe cause is
uncertain, and treatment other than contra! of the diabetes
is probably not indicated. Jhese young diabetics are al sig­
nificant risk of developing proliferative retinopathy.
Cranial N erve Abnorm alities
Cranial nerves III. IV, and VI palsy can be seen in patients
wilh diabetic microvasculopathy. The vasa nervorum sup­
plying the nerves are affected by diabetic changes reduc­
ing blood supply to (he nerve, resulting in cranial nerve
palsies. Mbs! cranial nerve palsies recover spontaneously
within 3-6 months.
tris
lhe excess accumulation of glycogen in the iris epithelial
tissue makes the iris boggy. They dilate poorly lo mydri-
atics. In addition, sympathetic changes that occur in the
nerves supplying the iris muscles also cause poor dilation
in some patients with longstanding diabetics.
C ilia r y B o d y
lixcess glycogen accumulation in the epithelium of the cili­
ary body can he seen histologically as vacuoles.
'lbe value of rigid control of diabetes in preventing or
reducing ocular complications Was controversial till the
results of the Diabetes Control and Complications '['rial
study were released. Diabetes Control and
Complications Trial Research Croup, in a long-term fol­
low-up 5Llidy of 1441 patients with IDDM (726 with no
reLinopalhy at baseline and 715 with mild retinopathy),
randomly assigned lo intensive therapy versus conven­
tional insulin therapy, demonstrated a 76% reduction in
the adjusted mean risk for the development of retinopathy
in the intensively treated group as compared lo the group
receiving conventional therapy.^1' they further demon­
strated a slowing of the progression of diabetic retinopa­
thy by 54% and reduced the development of proliferative
retinopathy or severe nonproliferative retinopathy by 47%
in the intensive therapy group. They confirmed the previ­
ously reported initial worsening of retinopathy lhal occurs
durmg the first year of intensive treatment but found thal
it often disappeared by IS m onths^ 1,835 Whereas lower­
ing of blood lipid levels with dietary and drug therapy may
reduce the number of yellow exudates in diabetic retinop­
athy, its value in preventing visual loss is uncertain.6^ * 37
Several randomised controlled trials of administration of
aspirin and sorbinil (aldose reductase] have demonstrated
no beneficial effect on the course of diabetic retinopa­
t h y '''■ One trial, however, found that aspirin alone
or in combination with dipyridamole significantly slows
the progression of microaneurysms in early diabetes.1'' A
irial concerning liclopidine (an lip Iale let agent) demon­
strated a favorable effect of the drug in reduction of pro­
gression of background diabetic retinojfetby,Bi's
In spile of the many changes (hat have occurred in the
treatment of diabeles. the Wisconsin hpidemiologic Study
of Diabelic Retinopathy reported that there had been Jil-
lle change during the previous Щ уели in (he incidence
and progression of diabetic retinopathy.'1'1' They found a
10-уелг incidence of retinopathy 79%, 67%), pro­
gression of retinopathy (70b, 69%, 53%), and progression
to proliferative retinopathy (30%, 24%, 10%) were highest
in the group diagnosed before age 30 years, intermediate in
the insulin-taking group diagnosed at age 30 years or older,
and lowest in the non insulin-taking group, respectively
Renal and pancreatic transplantation and hemodialysis
may have a favorable effect on diabetic reti nopat by.й*ам|
Other medical problems, particularly hypertension and
pregnancy, may exacerbate diabetic retinopathy.:’,'1i’"i''l',">
" '
The risk of development of diabetic microangiopatliy may
be related to HLA-associated genetic factors."
Hyperglycemia and diabetes do not appear to increase
the likelihood оГ (he development of age-related macular
degeneration.1'I:‘
A recent report from the Wisconsin group on preva­
lence of diabetic retinopathy in the USA [2003-200S)
lists prevalence of retinopathy al 2fl.5% and vision-threat­
ening retinopathy at 4.4%. Non-Hispanic black people
had a higher incidence compared Lo non-I lispanic white
individuals. Male se.\, higher lib A lt!, longer duration of
diabeies, insulin use, and higher systolic blood pressures
correlated independently with higher prevalence of diabetic
retinopathy.^'14
DIABETES MELLITUS, DIABETES
INSIPIDUS, OPTIC ATROPHY AND
DEAFNESS (DIDMOAD,
W O L F R A M S Y N D R O M E )_____________
Wolfram syndrome is an autosomal recess ively inher­
ited or spoaradic type 1 diabetes that is associated With
nephrogenic diabetes insipidus, progressive optic atro­
phy (I'igure 6.531.), deafness, anosmia, gonadal dysfunc­
tion, and neurogenic Ы adder.F Other ocular features
include pigmentary maculopatbyr congenital cataracts,
and itystagmus^ ^ Si Mutations of the VVF5J gene that
encodes wolfram in, a transmembrane glyoco protein of the
endoplasmic reticulum, are responsible for the condition,
lhe prognosis for life is limited due to the secondaiy com­
plications such as hydronephrosis and renal failure, wilh a
mortality rate of 63fl/h by age З З .^
R A D IA T IO N R E T IN O P A T H Y
Structural and permeability alterations in the blood vessels
of the retina and optic nerve that develop months or sev­
eral years after X-ray irradiation of the; orbital region may
cause toss of visual function (Hgure 6.57
Ophthalmoscopic alterations in Lhe retinal vasculature
include lhe development of focal arteriolar narrowing,
cotton-woo I patches, Lnicroaneurysms, dilated capillary
channels, perivascular shealhitig, irregular loss of the reti­
nal capillary bed, intraretinal exudation and hemorrhage,
and cirdnale exudation (figure 0.57). 'Ihese changes are
identical in all respects to diabetic relinopalhy. They are
usually most marked in lhe macular region, and. loss of
centra! acuily may be primarily a result of C M t, yellow­
ish exudative maculopathy or loss of the perifoveal capil-
Eaiy network Retinitis proliferans, optic disc new vessels,
vilreous hemorrhage, relinal detachment, rubeosis, and
glaucoma may evenIlially occur. Subretina! neovascular­
ization lhal in some cases may he derived from the retinal
circulation occasionally develops. bluorescein angiogra­
phy highlights the structural, and permeability alterations
of the retinal vasculature (figure 0.57). lhe latent period
until lhe onset of relinopalhy after irradiation therapy is
slightly shorter in patients receiving the episcleral cobalt
plaque treatment than in those receiving external-beam
irradiation, and is more prolonged after irradiation of
periorbital than of orbital tumors."'i:''J-,!l'J i?l 'lhe retinopa­
thy may appear as soon as (■ >months or as late as 5 years
or longer after irradiation Ufcatmen£3Sli'6' ] lielinopalhy
may develop after as little as 1500 rad of externai-beam
irradiation, but usually 3000-5500 rad is necessary lo
produce changes.s,i Lower doses of irradiation may pro­
duce retinopathy in patients receiving chemotherapy eig.,
1200cCy tola I-body irradiation after bone marrow trans­
plantation. and in patienls and experimental animals wilh
diabetes melliLus :: High dosages of cobalt plaque
therapy (mean dose of 15 000 rad delivered lo the fovea)
are required lo produce the same changes/"1
Visual acuity loss after irradiation may be caused also
by acute irradiation oplic neuropathy that is often char­
acterized by swelling of lhe optic disc, peripapillary hard
exudales, hemorrhages, subretinal fluid, and cotton-woo!
ф о ^ а к л б д а - в д fluorescein anjyography in patients
shews evidence of optic nerve head ischemia with superfi­
cial vascular noEiperfusion accompanied usually by changes
in the neighboring retinal blood vessels. l>isc swelling usu­
ally 1asls several weeks to months and is followed by optic
atrophy. Loss of acuity in these patients is usually severe
hut in some cases may partly improve with resolution of
the disc edema.:",IJ Oplic disc swelling and retinal changes
fe.^7 Radiation relinopalhy.
A and B: A 37-year-old whiLe man dtfveloped m acular
ttdema and exlensivn1 nhlciroanetJrysifraJ Spirmatlfin in bo ll1
eyes jjecdftdaiy to X-ray madia Lion of a recurrent basaJ cell
carcinom a of Lhe nose. Visual acuity in the left eye was
20/30. NoLe lhe local area of serous detachment of the
relina surrounded by a yel IOwl sb exudate (arrows:- al Lhe
su perokim рога I margin ot Che optic nerve head A), Early
an^io^aphy demonsLraled multiple microaneurysms lhal
1л1-ет showed evidence o f dye leakage ■Ltl. Sim ilar changes
□troUrred in Ihe opposite eye.
С and D: Extensive cystoid m acular edema IL M E ) with cir-
fijna.te relinopaLhy caused by X-iay irradialion therapy oi
n caitirram a of lbe anlrum in а 53-year-old wom an whose
visual acuity Was 2CV50 (Cl, Angiography 6bowed rtiicftf
aneurysms and dilation and parlia! Io sf et retina! capiilJaries
in lhe temporai ball of Lhe m acula. O n e hour after dye injec­
tion, angiography showed sLaininj; of Lhe serous fluid in Lhe
oilier layers of Lhe relina in a lypical paLlern o f C M E. Thirly-
Lwo monlhs afler xenon pholocoagul.it ion itD. visual acuily
was 20/3(1. There was no longer any angiographit evidence
ot C M E.
E—H : X-ray irradiation relinopalhy assoc iated with exudative
and hemorrhagic m acula pal hy ii> lhe right eye (E) and a sub-
hyaloid hemorrhage in 'iiu leM eye ■;FJ. Angiography showed
loss uf the juxtafoveal retinal capillaries bilaterally (G !■and
proliferative retinopalhy (arrows, H ) in the fefl eye.
Stability of radiation retinopathy over 3 years-
]-L: TГ: у 44-year-oid male with liidiatJon roLanopalby niain-
Lai ned a vision of 20/25 and 20-20 respect its^y tivtir more
Lhan 5 years of fo]lc*w-up. Scattered microaneurysms and
in iciO vasC liw abnormalities were p holographed in L)olh
eves in 2005 i and JJ. Three years laler ixjLh reLinas appear
relatively u n c handed W ilh minimal ^Iteration in the appear­
ance of lhe microaneurysms and Ihe mienjvasc ular changes
(K and L). H is vision remained unchanged in both eyes.
iA - l> . I r 'ii n L . l i v ' I'OljiFi.. A .m r.T iL .in M iji.liL .il A M ii J L i il J u n . .'VII ri^.hl:-;
r u it ir v i.'t l. I
may be absent in patienls with acute severe visual loss jn
one or both eyes occurring usually !- ] 5 years after irradia­
tion of parasellar tumors."1'1 L'hese patients typically show
visual field loss indicating optic nerve or chiasmal involve­
ment. Contrast-enhanced MRl and orfcilal ultrasonography
are invaluable in identifying the sites of radionecrosis of
the optic pathway and may obviate the necessity for biopsy
to eKclude recurrence of the primary tumor or a radiation-
induced tumor/ Some patients who have received
irradiation treatment lo Lhe chiasmal region may experi­
ence abrupt lale-onset visual loss in one or both eyes 4-35
months after receiving irradiation doses of less Lhan 200 Gy
daily and less than 6000Gy total dosage." : lhe visual loss
is permanent and no treatment is effective.
 I iigh-dose irradiation dellttrfct} to Lhe choroid and ret­ 6.5S Sic kte -cell re I iг opa Lliy.
ina via episcleral plaques will cause post irradiation atro-
ph ic changes in the choroid and pigment epithelium in
addilion lo lhe relinal vascular changes mentioned prevf-
ously/'"^* " K:' lbe size and location o i Lb-e tumor and the
amount of radiation delivered afTeel lhe incidence of radia-
Lion retinopathy, in a study by E\aul Finger only one eye of a
patient with A tumor in the anterior uvea developed radia­
tion retinopathy^ while 52% of the posterior choroidal
melanoma patients developed radiation retinopathy, lhe
radiation reLinopaLhy occurred closer to the tumor closer lo
the macula and the optic nerve, and more often in higher
metabolic posterior relina than nasal or anterior retina.
In a similar study by Cundu/ et al. of 13СЮ patients with
posterior uvea! melanoma, radiation retinopathy devel­
oped in 43.1% of patients; 5% had nonproliferative radia­
tion retinopathy at 1 year and 42% at 5 years, E’toliferative
retinopathy occurrcd in J % at 1 year and S % at 5 years.
Tumor margin of less than 4 mm from foveola had the
highest incidence of radiation retinopathy along with radi­
ation dose greater than 2frQcCyyhour lo lhe luiuo- base.4" '
In humans and experimental animals the principal histo­
pathologic changes caused by X-ray irradiation Involve loss
of lhe retinal capillary endothelial and perithelia I cells, cap­
illary occlusion. dilaLion arid hya Ianimation of thick-walled
A—C : Subretinal arid ргегеНплЕ macular hemorrhage in an
8-year-old black boy wrth sickle-cell hemoglobin С disease.
Anyiogjapby showed nonperfusiun ol the retinal vascular
bfed temporal lo lhe m acljJiJ i H j . Several m onlht I л lei lhe
Mood |iarl!y cleared, leaving лп iridesconL piemen Led pate h
□E hemosiderin And depi ^mentation o f Lhe relinal pigment
epithelium (C!:.
D-F: A( L ile Iом? of cenlral vision occurred in lHis- man w ilh
sickle-cell hemoglobin С disease. Note the subirternaT lim­
iting membrane berbatorrtas i arrows, L3i. A palch of fme
orange hemosiderin crystals was locaLed in the superficial
relina Iairowheadsj ■superior Lo a Jarge sunbursl paLtern
of pi^menl. lhure was eWtfehsive relinal capilJarv nonporfu-
Hicjn Ihrou^houl lhe Lemporal fundus, including lhe ВГпрогн!
macuEar area LE and FI. W ilh in 4 monlh-s lhe hematomas dis­
appeared and he recovered 20 f2% visual acuilv.
C and H: F\]ripheial salmori-palch hemorrhage before imd
afl-er parLial clearing ol lh e blood.
1: " 5tinI>Li-rsI" pigmenl Йар! with surrounding depiym enlation
a I Lhe sile of a previous relinal hemorrhage.
I and K: Peripheral proliferaLite retinopathy at the junclion of
Lhe perfused and nonped n-sed rciLina. Note early staning of
Lhe neovascular "sen tan."
L: Hislopalholo^v ol л "sea fan" o terlyin ^ lhe peripheral
пол pen used rtlina.
|L. cu ulu sy ill a>r. W. HkhiiryJ Cj-гщип

collateral channels- focal ischemic retinal infarcts, intrareti-

nal exudation, and inlrarelinal and preretina I neovascular- StC KLE-C ELL R E T IN O P A T H Y _________
iiiation.^41^41’7'^'00 Smaller vessels show thickening of the
walls by fibrillar and hyaline material. Mild myointima! Jilack patients wilh homozygous sickte^ell disease (SS),
proliferation of both the choroidal and central retinal arter­ hemoglobin SC disease (SC), and sickle-cell thalassemia
ies occurs.4'^ "1 'Ihese changes are occasionally sufficiently disease (S-lhal) and hemoglobin SO Arab"" may develop
severe lo result in occlusion of the central retinal artery.J' " occlusive vascular disease of Lbe peripheral retina that is
lh e outer retinal layers are more resistant lo irradiation associated with circumferential arteriovenous commu­
damage, lh e pathogenesis of radiation retinopathy is con­ nications, retinal neovascularization ("sea fans"), and
sidered to be loxiriLy lo the endothelial ceJEs. rlhe toxicity is focal intraretinal and sub retinal hemorrhages (\salmon-
progressive and occurs even after several years of radiation. patclT hemorrhages] at the juncture of the perfused and
Some eyes show no or minimal progression of the radiation nonperfused retina [E'igure 6.3Rj ' These latter
retinopathy even after several years (Figure 6.571-1.]. hemorrhages (J'igure 6.5#A and П). which occur near act
'lhe patients with exudative retinopathy caused by Local­ occluded arteriole, resolve and leave either an iridescent
r/ed capillary changes outside the papillomacular bundle patch of hemosiderin [E'igure 6.5БС, G, and H } or, if the
may be helped by pholocoagulation (figure 6.57C-J-']. blood extends beneath the retina, a black patch of hyper­
l>R[>may be of value in patients who develop severe prolifera­ plastic R r t {"sunburst" spoL&J (I'igure G.S&D-Ev and J)
tive retinopathy;ы Treatment of irradiation optic neuropaLhy or a byperpigmented scar. "J1 Ihese may be mistaken for
is generally unsatisfactory although some patients may expe­ A^'.il лпмл ■'I clioL'iori'Linitii. J:luorc-scd3t angiographic
rience restoration of vision after administration of hyperbaric evidence of peripheral retinal vascular occlusion develops
oxygen soon after the onset of visual fcns$£et,,,Ml Radiation in ПОЯ-b of children with SS and SC disease by the age of
maculopathy and macular edema with lipid exudates can be 6 years and in by age ]2 years.” ' " v Sanders et al.
Lreated. local laser photocoagulation lo the microaneurysms found Lhe mean largesl diameter of the f-'A7. in patients
has improved vision and decreased incidence of further with SC and SS disease was J .Omm compared to 0.61 mm
vision loss. Most recently, use of bevacizu mab has been con­ in normals."-' 'I'here was no significant difference in the
sidered. Jhe treatment is followed by reduction relinal hem­ FAZ diameter within the sickle-cell group in regard to the
orrhage. exudation, and edema. Visual acuities either remain degree of retinopathy, type of sickle-cell disease, or the
stable or improve in mosL patients.""’’''''' visual acuity.
 Despite lhe frequency of development of retinal vas­
cular changes, they cause visual Ioss in 10% or fewer
of patients with SC and SS disease.!tLfi-9Lfl Visual symp­
toms are most frequently caused by vitreous hemorrhage
derived from the retmafc neovascularization [E'iguies
6.SS J-L and 6.59C and both of which are more likely
to occur in males between the ages of 20 and 39 years...
and in patients with SC rather than SS disease. 503 IJI
Some patients, however, initially experience acute Eoss of
centraE vision caused by occEusion of one or more para­
central arterioles (i'igure 6.60A-J:], They have multiple
patches of ischemic retinal whitening that disappear in
several weeks. Angiography shows loss of localized areas
of the parafoveal capillary- network (I'igure G.GOD-F and
6.61 A-D) .These paracentral occlusive vascular changes are
more likely to occur in SS than in SC d i s e a s e . " I t
is probable that many of the small mtcrovascular changes
seen in the parafoveal capillary network in asympLomalic
sickle-cell disease are the resulL of minuLe arteriolar and
capillary obstructions Evidence of juxtafo-
veal capillary obstruction may occur in as many as 29%
of patients wilh sickle-cell hemoglobinopathies,10'"1 but
has been observed much less frequently in the patients
in Miami. Asdourian and coworkcrs'"'1 noted continuous
remodeling of the macular and paramacular vasculature
in such cases. Loss of central vision is occasionally caused
by occlusion of the central relinal artery" \ occlusion
of the centraE retinal vein (see I'igure 6.74A-Fj,J(l''i macu­
lar hole fdfttiati0n, usually associated with retinal tradion
caused by proliferative re tin o p a th y su b re lin a l and pre-
retinal bleeding from retinal new vessels al the junction
of the perfused and nonperfused retina that in some cases
may extend posteriorly into the macular areaJ"'' ; trac­
tion retinal detachment {Figure 6.GIG and H J; rhegmatog-
enous retinal detachment (i'igure 6.5yG]*~s; neovascular
g l a u c o m a retrobulbar ischemic optic neuropathy'"'1;
possible choroidal infarcts (iigure 6.601-L); and, rarely,
exudative retinal detach meat [E'igure 6.61 I).' ■ Macular
epi retina I membranes, which occur in approximately
4 % of patients with 55 and SC disease may he respon­
sible for subnormal visual acuity.1,1" " '' AJthough angioid
streaks occur in as many as 22% of patients with SS dis­
ease and less frequently in those with SC disease, rarely
are they associated wilh central vision loss caused by cho­
roidal neovascularization (Figure 3.32C-! and 6.S9H and
P) 334j9is [ПС[^епсе of angioid streaks and retinitis pro-
Liferans increases with age. I",r'
Other ocular findings occurring in sickle-cell dis­
ease include optic disc neovascularization.'" hair­
pin neovascular loops, 1''14 spontaneous peripheral
chorioretinal neovascularization,''' occlusion of the pos­
terior ciliary arteries,"l:" ' 1 pseudocapillaiy angiomas of
the r e t i n a , i s c h e m i c Infarction of the optic nerve
secondary to eEevated intraocular pressure/''1" 945 isch­
emic optic neuropathy in normotensive eyes/'41' and focal
t>.n9 Sic kEe -cell ret in (jpa Lhy,
A and B: A 10-yea r-oEd boy w ilh sickl-e-celI (Ь5) disease
WHi asymptomatic and seen With a vision of 2 0/20 during a
screening е к а т . There w ere ли retinal hemorrhages, scars,
new vessels. or nonperfusion. JJolh I urn porn I periphr;ral
small Vessel? wore prominent, suggesliny dilated capillary
bed and stow flow in these vessels in response to relative
tissue hypo\ia. rhe dilated capillary bed is Visible on the
angiograms in the temporal periphery o f both eyes .4 and 0}.
С and □: This 28-year-o3d with H b SCI disease had a flat
relinal neovascularijalion in Lhe upper nasal quadrant o f the
left eve wiLh nonperfusion at the retina anterior to il fArrow
Cl. In the superolemporal quadrant was an N V E with partial
auloiiivululion [Arrow t?l and a pigjiitMi Ied choriorefbi'aj star
a I Lhe silo of a previous hemorrhage (D).
Angioid streaks rn sickle-cetE retinopathy,
E and F: This .5:5-year-oId m ale w ilh HEi 55 disease had a
best-corrected vision at 20/2(1 in each eye. Angiojd s lre a K
were seen radiating from lhe oplrc disc in Eiolh eyes (E
and L ). There was no evidence of pallern dvslrophy, peali
d'orange, co m ^ s, -choroidal neovascularization or skin
changes, thus eliminating pseudoxanthoma etasticum.
С and H: This 54-year-old male Irom C h a n a presented w ilh
sudden I(k s of vision in his right eye lo couni fingers: Jb O B
of peripheral relinal n-onperfusion was seen assthciated w ilh
several auloinlarded raiserl and flat пей vascular tLifts, lhure
were ill,rue lears in Lhe interior and ml'erolomporal relinal
periphery cuasing the retrnar detachment JG J. The left eye
had peripheral пол perfusion lo a leaser degree arid auloin-
voluted new vessels (H i. Vision- in lh e LefL eye was 20/20. He
underwenl a pars plana vilrectom y with silicone oil place­
ment as lhe interior vitreous e*tremek- adherent La lhe
avascular relina.
capillary stasis in the inferior conjunctival cul-de-sac and
optic nerve head/'1 Ihese taller two findings are help­
ful in making Lhe clinical diagnosis of sickle-cell disease,
which ultimately requires hemoglobin electrophoresis for
confirmation. Coldbaum described a peculiar light reflex
seen when viewed via an indirect ophthalmoscope of
(he thin temporal retina resulting from posterior retinal
infarcts. "11' This is illustrated well on OC1' (Kigure 6.61 E\
and t-'). Monocular signs and symptoms, including mus-
cuhjskeletal and joint pain, abdominal discomfort, cho­
lelithiasis, and episodic anemia, that are often present in
patients with SS disease are frequently minimal or absent
in patients with SC disease. Ocular complications, how­
ever, are more frequent in patients with SC] disease. Eiare
forms of sickle-cell hemoglobinopathies also may be asso-
ci ated w ilh ocu lar com pI Lcalio П5.'у' '■"'"'3 1'1 Reli na I vascul ar
changes rarely occur in patienls with sickle-cell trait unless
they have additional systemic diseases that affect the ret­
ina or other relinal vascular diseases."' ''' Cass has seen one
such young patient who developed extreme peripheral
proliferative retinopathy and recurrent vitreous hemor­
rhage after initially developing bilateral central retinal vein
occlusion [see Tigure 6.74).
 Paaents with StI- and S3 disease prior lo the development
of proliferative relinopalhy may demonstrate evidence of
со Ip: vision abnomuLitici*, electron! inograp hie changes.,
and abapntialitjes of retinal vascular autoregulalion.' '■ ' '
There is a predilection for spontaneous regression or
autoinfarction of retinal neovascularization in sickle-cell
d Js ™ ^ f 9^ ^ №Sl?,9jJ,,'9S6 This may be more common in
S i disease."1' E-'or this reason, treatment Is probably nec­
essary only hi patients experiencing vilreous hemorrhage.
In such palients, focal pholocoagulation or cryotherapy
applied directly Lo areas of neovascularization nr scalier
treatment in zones of retinal vascular nonperfusion are
usually successful in causing regression of the new ves-
use of lhe fffider
technique of occluding neovascular fronds is associated
with a significant incidence [94% ) of posttrealment devel­
opment of choriovitreal neovascularization and should
he avoided in favor of scatter trealmenL to the periph­
eral zones of retinal capillary nonрегГшю n 4lo" Ct|
Posllreatmenl choriovitreal neovascularization may result
in further vitreo retina I complications and permanent
loss of visual function Other postpholocoagula-
Lion com plica lions are the development of choroidal neo-
vascularkzalEon/H4;^ r-s^ № :’ choroidal ischemia,'^1 and
relina] holes.''^' Scleral buckling procedures, vitrectomy,
and Md:YAG laser vilreo lysis are techniques used in these
palients with rhegmaLogenous nind Iractional retinal
detachi(3^OTx lixchange transfusions, formerly done
before sclera] buckling procedures lo reduce the chance of
severe ocular ischemic complications, probably should be
abandoned since the development of newer procedures for
managing relinal detachment. ''ил " 1
fc.bG ReversibEe macular i nfare tie ri in sicfele-tell
relinopalhy.
A-H: lliis 2 4 -year-o-l(I R e im a n t a m e m Гог a той lin e c x a n
a n d r u l e d a rig h l-e y e fie ld d efect w h e n sh e lo o k e d u p . i h e
saw 2 О Ч О О o n th e right a n d 2 0/20 o r the lefl. B ra n c h reLf-
naf a rle ry o c c lu s io n s w e re seen in (he rig h t m a c u la a n d
nasal relin a ( A Lind IS I. T h e la r Le m p o M l p e rip h e ry of. lh-е ri^ h l
s h o w e d va s c u la r o ct I us io n :C l . A n g io g r a m s h o w e d d e la y e d
il i i n ^ o f lh e in v o lv e d relin a l arlriolHS. W h e n e x a m in e d 1 a n d
.3 W eekij later the vis io n h a d im p r o v e d m a r g in a lly 1o 20^2 00^
lh o relina w as IransparenL a ^ a in , a n d Ihe vast u !a r p e rfu s io n
h a d fe -e s la b lis h e d in the right m a c u la ( H ) , She w a s k n o w n to
h a v e H b S i disease w ith several crises.
Choroidal ischemia in sickle-cell retinopathy.
I—Ll This 4 2 -y e a r-o ld A fr ic a n A m e r ic a n m a le w a s seen With
p o o r v is io n in b o th e y e s Гот a fe w y e a rs . His- b e sl-co rrticLe d
vis u a l a c u ity w a s 2 0 / 2 0 0 in e a c h e y e . B o th m a c u la * h a d
Ih in n in y w ilh p ijjm u n la lic m a1 the relina ] p ig m e n t e p ilh e lia l
level I a n d J); A n a l d i u ^ m re v e a le d p o s s ib le ch ori o ca pi I-
laris loss in the m a c u la , p o s s ib ly Iro m c h o ro id a l Lnfarcls sec­
o n d a r y Lo s ickle -ce ll disease (K a n d L j.
.Л-H, кшЛту Ы IJr. Will;.LinМк'к:г. Л.,i■
■
I LJ. Altu Y.innu^i. Ljvvrcinci.-
L . T b t R je lln a l A lin s . S a u n d c r i 2 0 I D r 9 7 B-0 -7{ 12( } J 3J [ } - 9 , p . 4 7 2 . U L ,
CCUrtM'tLJr. H.lliI Mci 'irx r^
1Ъе differential diagnosis includes Hales' disease, FtVH,
retrolental fibroplasia, sarcoidosis, inconLinenlia plgn^nij^
branch relinal vein occlusion, talc relinopalhy chronic
myelogenous leukemia, uveitis, pars planitis, radiation ret­
inopathy, aortic arch syndromes, carotid cavernous iislula,
diabetes, and collagen vascular disease.
5j'ckfc-Cdl Rctinvpatfuf 5b I
 Constant remodeling of lhe Vascular tree secondary
to micro infarcts and micro-occlusions, especially in the
retina temporal lo the nucule has been noted (L;igure
6.61 A-[>J. Cioldhaum described the relinal depression
sign indicating a small retinal infarct temporal to the mac­
ula.''' ' 'lliis is best seen by indirect ophLbalmoscopy With
a deflection of the light reflex More recently, this has been
documented by O C i findings. shdJWtrtg the temporal fovea
Lo be thinner than the nasal fovea (L:igure 6.6] E and J-'}.
In a study by Lima et al.,' 3! con fundi va I vessel altera­
tion was not influenced by age. gender, felal hemoglo­
bin estimation, serum creatine albumin lewis, presence
of alpha-thalassemia or beta-gjobin gene haplotypes.
However increasing the conjunctival vessel alteration was
seen In patients with hemoglobin less than У.0 grams per
100 ml. hematocrit of less than 36.74%, and Sb phenotype
of sickle-cell anemia, suggesting that Lower hemoglobin
and lower hematocrit and Sb phenotype are risk factors
for conjunctival vascular anomalies. Age over 17 years was
a risk for retinal vascular anomalies in sickle-cell disease
patients. Treatment of acute CRAG or occlusion of larger
relinal vessels can be done with immediate-exchange
transfusion, improvement of the oxygen-carrying capac­
ity, and deliveiy of lOO^o oxygen by nasal cannula or
other means, lhe occlusion of the sickle cells is wors­
ened by a mechanism called logjam where more sickle
cells pile up behind the initial site of ocdusionr increas­
ing the area of nonperfusion, including surrounding areas
for nonperfusion and occlusion. It is believed that similar
stagnation of cells occurs in the choroid as occurs in the
retinal circulation. Lhe smaller choroidal vessels Ln the
6.61 Sic kte c e ll re lin o p a lh y
A—F: This 23-year-old m ale from wesl Africa £jave я history
Dt diplopia and ё stroke that resuiled in Weakness o f Lhe k*fl
aide of his body. He was hospitalized for poor mentatkrfi.
W h en ho regained to list iousnoss bo nolrtd Subnormal vision
in +iit rigbL eye lhal improved lo a $|nall oxieni over lime.
W h en examined .1 yaari laler bolh maculav showed enlarged
foveal avascular zune (B and C) associated with micTova-s-
cular changes in Iho fovea I vessels (я). The p if lib e ra l relina
showed expensive nonperfusion Eli laterally hul no n ew ves­
sels ID.. The lemporai foveal rt*1iпл was linn compared Co lhe
nasal f o w j in boch eyes it and J-, arrows!.
G and H: Ajuloinlarction of the raised new vessels resulting
in gliosis and traction c l the leading arleriok^s in a patiEnl
with Hb SS disease.
I: r h ii 10-yeaг-old ^irl with slckle-cell disease was nsymp-
lom alic. she had an outer relinal/t/huioidal w hite lesion
associated w jlh surrounding subretinal fluid. 14 Ls likely Ibal
lhe yeliow lesion is subretmal or outer relinal dt1hurno^lo-
b in iied blood. The vellow patch and subrelinal fluid had
resolved sponlaneousJy whian she wan i6 - E x a # H d 2 months
later.
choriocapillary lobules are more prone to vaso-occlusion
by the effect of sickling on choroidal circulation [E'igurt
G.60L—[.). It is known from studies that the blood flow is
slower in patients with sickle-cell disease rather than nor­
mal patients. Et is also useful to monitor these patients
for desferrio^amine toxicity since many of them are on
chelating agents to treat (he iron overload from repealed
transfusions.4’ ^
P R IM A R Y R ET JN A L V A S C U L IT IS O R
V A S C U L O P A T H Y (EA LES' D IS E A S E )
A]though Eales originally described lhe association of reti­
nal hemorrhages i^'ith epistaxis and constipation, the lerm
"bales' disease" is now used to describe patients who. in
the ear]y course of this disorder of unknown cause, have
active occlusive vasculopathy affecting primarily the major
retinal vessels in the peripheral fundus and who laler
develop neovascu lari nation occurring along the posterior
edge of broad areas of periphery] retinal vascular occlu­
sion. ' ■ ,a: Most of these patienis are asymptomatic al
the time of the active occlusive vascu Iopalhy or ^vascu li­
tis/ xvhich cnay involve primarily the retinal veins, retinal
arteries, or bolh. If seen during this active phase of the dis­
ease, because of complaints of visual field loss, pholop-
sias, or floaters, fundoscopiic examination may reveal a
variety of pictures, including peripheral retinal perivenous
exudation, retinal hemorrhages and exudation, or retinal
periarterial exudation, arterial occlusion, and ischemic
retinal whitening. Because many patients are asymptom­
atic during the early active vasculopathy stages of bales'
disease., we have little information concerning the reIalive
frequency of the various fundoscopic pi dunes lhal occur
early in these patients, who later present with a similar
t'undoscopic picture of peripheral retinal vascular occlu­
sive disease (figures 6.62 and 6.63}. Salients wilh bales'
disease are typically healthy young men between the ages
of 20 and 30 years who seek treatment because of float­
ers or vision loss second ary to vitreous hemorrhage. The
hemorrhage is caused by peripheral relinal neovascular­
ization and in some cases optic disc neovascularization
[figure 6.62 ]-[.}. Occasionally, loss of vision is caused by
retinal capillary telangiectasis and C.ML [figure 6.62) or
macular pucker caused by an epiretinal membrane. Similar
changes in the peripheral fundus are often present in both
eyes. Although ihere is a higher than normal incidence of
6.62 tales'disease,
A —D: Recurrenl vitreous hemorrhage occurred in the right
eye of л 35-year-old man with 20^20 visual acuity. Гп bolh
eyes he had lar^e equatorial zones mf relinal capillary non­
perfusion anti геУ1iniris pjtblifefHnS as well as capillary lelan-
gicctasis i-п the Lemporril птасиЗл o f both eyes I arrows. A and
K). In the asymptomatic lelt eye be had optic disc neovas­
cularization >A . Angiography demonslTalud rrifrrirnil leakage
□I lbe tefwfljlectatit cnpiliaries in 1be macular areas ■1-51 and
staining o f the oplic disc and peripheral new vessel? (C and
D)_ rtin retinal pholocoagulation of the nonpertused retinal
/ones anti laler a vitrectomy were required to Stop lhe vilre-
ous hemorrhages.
E-H: This healthy 30-year-oFd man noted loss o f paracen­
tral vision in (he left eye. His visual acu ily was 2(Y1 5 bilat­
erally. Note the prominent papillary and j uk tapap i 11ary
lel.niLiiet l.14s. irregular n.irrtm n;.', or tin1 rdii>,il .■■t-i i1 .nn::
cotton-wool patches biEalerally (t and F^. He had extensive
oblilDTalbon ol" his peripheral retinal Visculatum in both eyes.
Angiography demonstrated extensive m icrovascular changes
and a focal area o f capillary nonpttrtubio-n fa now, H.I cor­
responding w ilh a patch ol" ischem ic whitening on lhe lefl
oplic disc. Soon afterward he began lo experience recurrenl
vitreous hemorrhages with peripheral and optic: disc n-uovas-
CLtlari^aLion that required panrelinal photucoagulalion and
vilrectomy.
I- L: Th it hen 11by younjj man e x p e r ie n c e severe; b ila k ia l
Ecus of vision associated with severe peripheral occlusive
retinal vein and arterial disease that extended posteriorly and
was assoc in kid w ilh exlensive pepl iterative retinopaLhy.
positive react inn lo lhe tuberculin protein, there is no evi­
dence that the ocular changes are directly related to active
tuberculosis. Jn most palienls examined before develop­
ing vitreous hemorrhage, there is minima! evidence of
inflammation in either the vitreous or retina. One or more
retinal neovascular fronds are usually found near the pos­
terior border separating (he anterior tionperfused retina
from the normal retina {Figure 6.6ЗА and H). 'Jhese retinal
vascular changes are usually more prominenL temporally.
 Huorescein angiography during the acute vascular
occlusive phase of the disease reveals evidence of severe
permeability alterations and obstruction lhat ttiay affect
primarily the retinal veins or the arteries. During the Iale г
stages of the disease angiography defines the zcrnes of loss
of the retina] vasculature and the remodeling of lhe reti­
nal circulation. Which often includes retinal neovascular­
ization along the posterior border of the zones of perfused
and non perfused retina (figures S.62K and I., and 6.63C
and D, |-L).
Tales'' disease probably is a heterogeneous disorder
that involves at least two groups of patienls. in one group,
who arc predominantly males, the vasculopalhy involves
primarily the relinal veins. In the olher group, with no
seK predilection., (he relinal arteries are primarily affected.
Ihese latter palients are probably part of the spectrum of
idiopathic hi lateral recurrent branch retinaE arterial occlu­
sion (see p. 4S2J. Recent folEow-up study of these palients,
who typically present wilh visuaE toss caused by mukiple
branch retina] artery occlusions caused by focal "arteri-
otilis" involving the posterior fundi, reveals a high inci­
dence of development of evidence of peripheral retinal
vascular occlusive disease and proliferative retinopathy.
Some of these patienls may develop olher evidence of
focal central nervous involvement."'1 Eividence suggests
a higher than nomial incidence of auditory and veslibu-
Ear abnormalities in these patienls wilh bilateral recur­
rent branch relinal artery occlusion as well as in series of
palients wilh E-ales' disease.'
Laboratory investigations of palients wilh kales' disease
haw Г-aikd to determine the cause of the vasculopathy.
Klevalion of the patient's serum alpha-1 acid glycoprotein
Eevels has been demonstrated in these patients during the
active phase of the disease."*5'litis is a non specific finding
that jnay be present in some patients with inflammatory
disease, malignancies, and Lissue necrosis. In a taige group
of patients from India with hales' disease, Kengaraian
and coworkers found two specific serum proteins, one of
Which was an an ionic peptide, that were not present in
normal control patienls.')Sl:
EaEesr decease,
A—G : This 29-year-old physiciлтл from India was Evaluated
Гит floaters in his right eye. He had no history sugj^eslive of
lulberc и Ios i s. There was а partly gliolic raised N V t in the
яapejolumporal quarIм nt, anterior to w hich was retinal non-
perf union. There '■v'era sheathed reLjnal veins in IKf1 infero-
nasal quadra nl and Еэпе choriorelircal hear IA and b5:. N o
areas of аСЙуе vasculilis w ere found. A fluorescein angio­
gram defined Lhe areas (]f nonpertusi-on sind neovascular-
Eiialion (C ^nd □). He underwent scalier laser № the areas
□E nonperfusion. A Uiberculosis skin lesl relum ed кЕгип^Зу
posiliver but a chesL X-ray was normal. He was Billow ed, the
new vessels repressed, and lhe vilreous hemorrhage cleared.
A year kiler he was seen lo develop several sniH^II relinal
hemorrhages and p7hlcE?iIi^ (affloW) in the lempotal periphery
и! the rEght eye (E). Since he now showed active vasculitis
with breakdown oE the blood-retinai barrier on fluorescence
angiogram 11 , he was Lreatetl w ilh an 113-monLh course е>г a
four-drui} anlilubenculous regimen and iapering dose ol oral
sluroids for 2 months-. The vasculitis and reflinal hemorrhages
cleared and his vision remained aI 20/20 (G). The lefl eye
was normal throughout.
H-L; This healthy 5 ]-year-old m ale gave a 4-monlh history
of progressive loss of vision rn holh eyes assaciaIed w ilh
severe! occlusive reLinal vastuls^ disease affecting primar­
ily Lhe retinal arterial system. Recently lie had developed
mild vilreous hemorrhage caused by peripheral relinal neo-
vascularination-. Hib visual acuily was 20-'-(00, rigbl eye,
20/200, let* eye. Note Lhe multiple affifitomafdub plaques in
lhe arterial walls (H and I ■ , pallpr of the oplic discs, and Ihe
widespread dol and blot relinal hemorrhages. .Vledical and
neurologic evalualions, including magnelic resonant ec in>a^-
in^ of Ihe brain, w ere negalive. AngiogjaplTV revealed exten­
sive loss o f the rh in al m icrotasculalure in Ehe m acula areas
and peripherally |-L). There was marked microaneurysmal
change and laEe staining in Lfie area ot pari Iу fieri usnd relina
posteriorly. Liolh eyes subsequently required pan retinal pho-
Locoagulalion and vitrectomy.
IH -L , cLiur1(j:-y tif l>r. l-мпк J. СыБиНа.)
 'lhe diagnosis of Hales' disease should be reserved for
patiqob with no evidence of other discLises th al can pro­
duce lhe identical fundus changes. Ihese diseases include
sickle-ceH disease, diabeies, collagen vascular disease (Figure
6.MA-K}. Incontinentia piginenti, ROJ? [see p. 5Л)], FEVR
(see p. 576}f branch relinal vein occlusion,
FSHDp sarcoidosis, pars planitis, serpiginous choroiditis {see
pp. 962-368), frosted retinal angiitis (see p. 350), ulcer­
ative colit Is.-... chronic idiopathic central serous chorioreti­
nopathy (see p. 76J, and a familial syndrome that includes
young women wilh graying of lhe hair., poikiloderma, and
idiopathic nonarteriosclerotic cerebral calcifications.™
(See discussion of reLin.nl vasculitis in Chapter 1].) Patients
wilh JTCVA.N syndrome haw a peripheral obi iterative vascu-
Lopathy that resembles Kaies' disease in all ways except for
the presence of arterial aneurysms [ilgure 6.5(1 and 6.51).
WheLher these two conditions are causally related is yet lo
be determined.
The natural course of Hales' disease is variable. In some
patients spontaneous occlusion of the new vessels occurs,
and in others recurrent vitreous hemorrhage and progres­
sion of the occlusive vascular disease may lead lo tola I reti­
nal dctachmenl.
rholocoagulation of the non perfused peripheral retina,
avoiding lhe Eai^ge areas of retinal neovascularization, is
indicated in patienls experiencing vilreous hemorrhage.
In some palients with vitreous traction, a vitrectomy also
may be necessary. L’holocoagulation may be beneficial in
the few patients who develop CM£ or circinate rnaculopa-
tby caused by paracentral telangiectasia.
6.64 Collagen vascular disease associated vasculitis.
A—F: This 1S-year-otd m ale w ilh polyarthritis, circulat­
ing lupus anlicoajjulanl,. mi Ed Raynaud's phenomena, pro­
lei пипа, тлисиш inomljfane lesions, arid severe ischemia
chanjjlB of" till.1 dibits df holh hands developed peripheral
occlusive retinal vasculopathy affecting prim arily the venous
svslem IG-I). Ten ivtvks later there was extensive whitening
ot I ht* occluded retinal vessels i'll a r d proliferative retinopa­
thy (K and L). biopsy o f the kidney, liver, and femur repealed
arierilis.
Idiopathic oblilerative arteritis.
G-L: A 47-year-old Lai in Am erican male was seen for
blunt'd vision for 25 days associ a I ed w ilh few floaLers and
flashes of lijjhi. His vision was 2 0/20 on the right and 2 0 /3 0
on lhe Ief1. 1 4- vilreous cell-ь w ere seen on Lhe ileit. Vlost of
tEie retinal arleiioles bhowen patchy periarterial w hiten­
ing in bolh eyes associated w ilh few colton-wool patches.
Angiogram showed occlusion of lhe infenolemporal artorioJe
on lhe ri^Jil and infeTonnisaI arteriole -on lhe left, iyslem ic
work-up Гог lulierculosiis and collagen vascular disease was
negative. He received systemic steroids; lhe lell eye devel­
oped neovascular glaucom a and vilreous hemorrhage requir­
ing a tube shunt and viuocloinv. His final visual acuity was
2U/h0 and 20/40. The working diagnosis was bales' disease,
which may or may not lie the accurate tecrrt for his condition.
l A ^ F . f r L im If u ll c l j |J : Ci-L. L O L i r l u ^ v <>■ LJr. Ь :Ш 1 Ь п и ч л Е .)
R E T IN O P A T H Y O F P R E M A T U R IT Y
Prematuf^infants with a birth weight less than ISO tJgrants
and bom at less than 32 weeks of postconceplional Age are
at risk of developing E'he fundamental process
underlying the development of RD P is incomplete vascu­
larization of the retina, and the ophthalmoscopic find­
in g slem from this arrested development. Enuring normal
retinal developmenl, vessels migrate from the opiic disc
to the ora serrata, beginning at approximately 16 weeks of
gestation. Vasculogenesis transforms precursor cells inlo
capillary networks. Mature vessels differentiate from these
networks and extend lo the nasal ora serrata by 3(i weeks of
gestation and to the temporal ora serrata by 39-31 weeks,
lh e location of the interruption of normal vascutogen-
esis is related lo the time of premature birth, '['he clinical
appearance of the various stages of ROS> is related Lo lhe
location of Lhe vascular-avascular junction.
I4>r the purposes of defining the location and extent of
the retinopathy lhe International Classification of ROT
divides the fundus into two circular and one crescenlic
zones centered on the oplic disc; zone I (posterior pole
or inner zone) is a circular zone, the radius of which sub-
Lends an angle of 30° from lhe optic disc (the radius of
the circle is equal to twice the distance of the fovea I cen­
ter from the disc edge). As a practical approach for the
clinician, (he approximate temporal extent of zone I can
be determined by using a 25- от 2S-[> condensing lens.
Бу placing the nasal edge of the optic disc at one edge
of the field of view, the limit of zone E is at the temporal
field of view, /one 11 extends from lhe edge of zone 1 lo
a point langential lo the nasal ora serrata. /one Ell is lhe
residual temporal cre&cenl of retina anterior lo zone J]..■"■
Il’-;- l'x-l'iH of the disease is spLYiJial U' hours ■ ■i\ '.he
clock. Jhe stages of abnormal retinal vascular response are
as follows: stage 1 of this disease is associated wilh a flat
circumferential white retinal demarcation line caused by
proliferating primitive vascular endothelial spindle celts at
the junction of the vascularized and the nonvascularized
retina. Slage 2 is associated with widening and elevation
of the demarcation line inlo a ridge of tissue anterior Lo
the plane of lhe retina [E'igures й,65 and 6.6£>A-C;J. The
ridge may change from white lo pink as retinal vessels
leave the plane of the relina lo enter it. Multiple isolated
polypoid neovascular lufts [ лpopcorn” ) may occur near
the posterior edge of the ridge and occasionally in the
6.6". Re tino pa Lhy qf prem atu ri I у fRO!Tl.
A—C: FYeniatufifE in1;ml w ilh 1 R O I'. Arrows indicant?
nenvascLllaf' lufls ("popOirfnT) aiong thy poslerior tfdge of lhe
nedVascuraB ridge.
D-l: Mage 2 K O P in д prortiaLurp intant. NoLc lhth di laired
relinal vyirih and Ihe.1 m uiliply round noovasuular lulls (л'рор-
corn'T) (arrows, D—I) ptis-loricjr 1c Lhe пeovaBful л г fid^e and
on lhe optiu dine: iF I.
] rind K: Histcragfiology ol" lilaye 1 KC?F’ shuwjn^ lhy anterioi
io n -и t)f proliferaLiijn of priniilivt! теьи гк’Етута! се53н in lhe
non vascularized roLina (arrow, 11 ,ind lhe inirareLinal and pru-
rtilinal neauastular 1iss-Lrt1-tombtisiritt lhe ridgp -.arrowheads-. I
poHleriof to thy avascular z!)nt\ The arrr?w in К iindicateb a nuo-
vascular lull ("popcorn"! arising from the vascularized retina
posterior Lo the ridge.
lA -i, rm m G ;in ju n u l ,il.1|ll;ii
posterior fundus (]:igure .Й.й5),Ю 04-14)18 Jhese neovascular
lufls are not considered part of the fibrovascular growth
required for slage 3. Microscopically the ridge anteriorly
is composed primarily of retinal astrocyte precursors lhal
stimulate the proliferation of main re endolhelial cells inlo
a capillary network [I'igure 6.65J and Stage 3 is
associated wilh extrarelinal Iibrovascular proliferation: ( I )
continuous wilh (he posterior aspect of (he ridge, often
causing a ragged appearance of the ridge: (2 ) immedi­
ately posterior lo the ridge but not always connected lo
it; or (3) extending into the vitreous perpendicular lo the
retinal plane, in some patients Lhe fibrovascular prolif­
eration begins nasally1'" ' "'Plus" disease is used to desig­
nate a more severe form of each slage of JtOR When any
of the stages of (he peripheral relinal vascular changes are
accompanied by evidence of progressive vascular incom­
petence, including dilation of Lhe poslerior retinal veins,
lorluosiLy of the retinal arLeries, iris vascular engorgement
pupillary rigidity, and vitreous haze, a plus sign is added lo
lhe slage."■'L1,|I|J" this definition was further refined to be
made only when sufficient vascular dilalation and Lortuos-
ity were present in at least two quadrants of the posterior
fundus.1021 Stage 4 designates a subtotal relinal detach­
ment.. either exudalive or iraclional. Stage 4A is used for
extrafoveai detach men Ls and 41i for detachments involving
lhe fovea. Stage 5 is associated with a total funnei-shaped
retinal detachment (E'igure G.67A-3’).
 An uncommon, rapidly progressing, severe farm of
ROFf is designated aggressive posterior ROP. Ef untreated,
it usually progresses to relinal detachment, oflen without
moving sequentially through the classic stages 1-3. '['he
characteristic features of this type of ROP are its posterior
location, anlerlor-segmenl vascular congestion, promi­
nence of plus disease out of proportion lo the peripheral
retinopathy, and the Ill-defined nature of the retinopa­
thy. IUJ'’ Most infants wilh ROP show partial or alл tost
complete regression of the retinopathy without treat­
ment. lypically by 45 Weeks of posiconceptional age, the
demarcation line and ridge may atrophy and disappear
as retinal vascular migration into the peripheral avascu­
lar zone resumes. Nearly all patients with stage ] and 2
ROP undergo complete resolution."vJ J,ess severe changes
Lli.it may accompany die mild ckv.tru i.il disease [stage Э]
Include mytrpia; amblyopia; strabismus: relinal pigmen­
tation; vitreous membranes; and equatorial folds at the
junction of a vascularized and avascular relinak:iJ:: i a jj
straightening of the relinal blood vessels In the temporal
arcade, wilh decrease in lhe angle of insertion of the tem­
poral arcades into the oplic disc; dragging of Lhe retina
and macular dispEacement, usually In a lemporal direc­
tion (figures 6.66A, В, D, and H and 6.67K}; and retinal
neovascularization occurring near the equator (Figure
6.G6I- L).lClJ,:-50::- Amblyopia may be caused in part by
arrest of Lhe normal postnatal development of the central
macula,:01^ 'lub |02L>occult hyperoxemic relinal necrosis,1'"11
and progressive RPli and relinal atrophy.l03ljL{U2 Peripheral
fundus changes include incomplete vascularizaLion of the
peripheral retina; abnormal, nondicholomous branch­
ing of retinal vessels; vascular arcades wilh circumferen­
tial interconnecting Lelangiectalic vessels (figure fi.671);
retinal pigmentary changes; vltreoretinil interface changes;
falciform relinal folds (Jigure 6.67k; vitreous membranes
wilh or without attachment to relina ( l:igure 6.67C and
I}; lattice Iike degeneration; irregular retinal breaks; pos­
terior displacement of the vitreous base; and exudative,
Lractlonal, and rhegmatogenous retinal detachment.
Pseudoexolropia usually accompanies the ectopia of the
macula {I'igure <3.66C.].1UJ''
Patients wilh mild to moderate degrees of cicatricial ROP
may later in life develop rftegmalogenous, lractlonal, and
exudative relinal detachment as well as pseudoangioma-
tous masses [Figure lb e exuda­
tive changes may resemble those seen in Coals' syndrome
caused by congenital relinal telangiectasis, angiomatosis ret­
inae, and FFVR (E'igures 6.66L and 6.671).ki:" Interestingly,
patients with a hislory of premature birth oflen shtnv a
significantly smaller FAZ*3 and absence of a normal foveal
contour, ihese changes likely represent develop mental
arrest of Lhe normal centripetal migration of retinal gan­
glion and Inner nuclear cells. They appear to be ittdepen-
denl of refractive error or relinal ablative LreatmeLit and may
be compatible wilh excellent visual acuity.1"'0
Other diseases that nilrsl he included in the differen­
tial diagnosis are H3Vti. incontinentia pigmenli, sickle­
cell relinopalhy, Kales' disease, diabetic retinopathy,
&.66 Relinopalhy pf prematurity {ROP).
A -С: D ra w in g of lhe? lefl m acula ;ind relirral VE^sels Icmpe-
rally in a premature infanl. Com pare A , before d r a ^ in j’, w ilh
EJ. NcLe the neovascular t-bmplefc :CJI Щ Lhe equator lempt)-
rjbi ly tind lliL1absence erf relinal VLisHels; beyond lhe complex.
D -F: KOh3 causing heterotopia ol lhe ri^hl macula it)' and j
retinal mid ex It1riding Iron, lhe lefL optic: dist to Lhe fern para}
peripheiy h and F-l. Nt)Le lhe absence o f relinal vessels in the
Lemporal re1ir>a (F.l.
G - K : Late mild cicatricial sLage of R O P causing temporal
i h.v.^-in'J, nl ilic i i;L;hl mai'ul.i .ind рнеиск uxotru hi,d К ; ,ind I I
in a 12-year-old f^irl whose visual acuilv mas 2ОП0. NoLe the
evidence of occlusive relinal vascular disease at Lhe equalur
LemporaNy I and J.i. A n ^ io^ a phy shrined a broad zone of
nelirral nun perfusion tem porally and sLainjn^ of die abnormal
vascular arcades juil p o ileiiu r to this- ^оп-e ;K;.
L : La te m ild cicaLricial E i O P c a u tjn ^ p e rip h e ra l CJoals' s yn ­
d ro m e fn a i 3 -y e a r-o ld m a n w h o s e b irth w e ig h I w as 2 Ih
(Q .SEtjjJ. N o t e the s u b re tin a l a n d i nlrareiEna f lip id e x u d a te
derivEtd fro m p e rip h e ra l i nlra neLi na] n e o v n s Lu l.iri^ i^ liD n .
lA-< . njurLtVr Ы IJr. Irstin Г. Flynri.'i
and the ectodermal dysplasia, eclrodactyly, and clefting
syndrome.
1Ю 11 has been reported in full-term infants,11'
though these diagnoses may actuaEly represent cases
of HliVR.
While improvements in maternal antenatal and neo­
natal care haw lowered the incidence of HOI1, low birth
weight and gestational age remain lhe most important risk
factors. Exposure to ambient light in (he nursery has been
proven not be a risk facto r. L0■
|-,
The role of oxygen supplementation in ROl1 pathogenesis
remains complex and controversial. Growing clinical expe­
rience suggests lhat lower, buL narrowly conLained. oxygen
saturations (R5-92',4) early in postnatal life significantly
lowered the incidence and severity ot" h'ewer
protocols for oxygen supplementation provide for age-
directed target ranges, in which salutations are targeted lo
85-92% until 34 weeks' poslconceplion, and then raised lo
У2- l(J0% after 34 weeks' posiconceptional age.llllH
'lhe majority of premature infants will develop some
ROP In al least one eye, and in mosl infanls, the disease
will regress spontaneously.LUL Screening for ROP should be
initialed no sooner lhan 31 weeks of postconceptional age
or 4-6 weeks of chronological age, whichever is later.
lhe median onsel of stage I ROP is 34 weeks' postcon-
cep Lion, and the median age of ROP requiring treatment
is approximately 36 weekti’ poslconceplion. M>" : Liser pho-
locoagulalion of Lhe avascular retinal periphery, in a near­
confluent pattern of spots, has been shown to reduce lhe
chance of unfavorable visual and structural outcomes m
infants with type I ROT. lype I ROE* was defined as; f ij
any stage of ROP wilh plus disease in /one 1; [2] slage 111
ROP in zone 1; (3) stage 19 or LIE ROE1 with plus disease in
ione 2. Huorescein angiography may be of value in dem­
onstrating peripheral retinal vascular changes associated
with cicatricial ROP and may reveal areas of retinal non­
perfusion requiring laser ab]ation.3lJrLW}l lDj5
 Converging lines of laboratory research and empiric
clinical evidence support Lhe rationale of targeted phar­
macologic inhibition o fV EG F as а treatment Гог advanced
1?ОГ. Intravitreal injection of bevacizumab [Avastin| has
been shown lo be highly effective in reducing vascular
activity and eliminating retinal neovascularization. primar­
ily in eyes with posterior disease and a guarded prognosis.
It has been used successfully as rescue therapy follow­
ing laser treatment- as an adjuvant to laser in eyes with
tin paired fundus visualisation due to anterior-segment
congestion, and as щогффЁегару.11
Although relinal ablation is effective in mosL cases of
advanced ROPj a significant number of these eyes progress
to reLinai detachment. Detachmenl Is often seen associated
with areas of incomplete peripheral ablation (skip areas) or
in eyes wilh inexorably progressive, usually postequatorial
disease. Contraction of neovascularization along the ridge
and growth into lhe overlying vitreous precede traclional
retinal detachment. Condensation of vitreous into sheets
and strands acts as a scaffold for further extension of the
hbrovascular tissue. Traction along the retinal surface and
contraction of the posterior hyaloid face contribute to dis­
tortion of posterior-pole architecture. 'lhe configuration of
Lhe relinal detachment in ROE3 depends primarily on the
Location of the ridge and the orientation of vectors of vil-
reoretinal traction. Traclional forces are exerted by contrac­
tion of the posterior hyaloid as well as in the directional
vectors intrinsic to the relina, from the ridge to the lens.
6.67 Stages of retinopathy of prematurity (ROP^.
A —F: Stages 1-5.
I . AbrupL end lo the vp^ssds, Ем'уогкН which is avast::.i lar
relina 'A ). 2. l^emarcalion :ле Eje(we.4.j n v a s c u lii^ e q and
avascular reLira ( В I. 3. Vascular gjowth over д ridge beflween
A s c lila r and avascular relina !CJl. .3 plus. J >il<ilucI and til.rtu-
ulis vessels pOstaflw Гсз lhe ridge, bignityirjj plus disease |D>.
4. C o rlra c tio r o f lhe ridge w ilh localized I где I io r detach-
menl ro t involving lhe macula \Er arrow). 5. TracJion relinal
delachm-urr! involving Ihie macula
G and H : Coats'-lilce response and H ad ion relinal detach­
ment in an Я-уедг-nid jjii] ivilh KC.3K. Nole lhe avascular
relina temporally and llie vascular alteration ir the posterior
pole on angiogTaphy :Hl.
I: Lo nlsr-like response with liptd accumLH.il ion pcftLerior lo
lhe ridge ll j.
j: Contraction ot the hyaloid where attached lo I he previous
ridge. Nolo lh e extensive avabcuLarity sflpiet'lorly.
K: A dull КОИ Mfith dragging of" lhe temporal relina into и fal­
ciform fold.
К j n u r c t i y Cjf U r . iT .IH C lil H cil l M i.i.J
iransvilreally from ridge to ridge, from ridge to ciliary body,
and extending from lhe disc stalk (i’igure 6.G6C-K}. Some
or all of the above components are present in КОP-related
retinal detachments. The configuration of the detachment
is determined by the relative force vector contribution of
tiactional component.'0^3Spontaneous reattachment of lhe
retina in slages 4 and 5 rarely occurs.1:1,1

F A M IL IA L e x u d a t i v e
V IT R E O R E T IN O P A T H Y
hbVK Is a hereditary ocular disorder first described by
CrlsWlck and 5chepens in 196У. It can be inherited as an
autos-orm*]-dominant, recessive or X-linked trait with high
penetrance and variable expressivity. il resembles RGP but
occurs in patients with no history of prematurity or neona-
Lal oxygen therapy■ ' in its earliest and mildest form,
areas of peripheral retinal whitening without sclera] depres­
sion, peripheral cystoid degeneration, vitreous band fbrma-
tion, vitreous traction, and minimal or no retinal vascular
changes are presenl in Lhe temporal periphery of otherwise
normal eyes. Peripheral retinal avascularityr retinal seovas-
cuEarijiation, disc neo\rascnlari^ation, fibrous proliferation,
exudation, and localized relinal detachmcnt in Lhe area
between the equator and ora serrata with traction and drag­
ging of the major retinal vessels and macula in a temporal
direction represent a moderately advanced stage of the dis­
ease (Ngure 6.6SC and C). Ihese changes cause retinal and
subretina] exudation [Coats' syndrome), vitreous traction,
retinoschisis, retinal hole formation, falciform retina! folds,
total retinal detachment, cataract, intraocular hemorrhage,
and neovascular and angle closure gjaucoma [I'igure
Loss of central vision may be caused by heterotopia of (he
macula, relinal striae, cystoid retinal edema, epiretinal
membrane, and retinal d e t a c h m e n t .I’seudoexotropia
caused by temporal dragging of the macula is frequently
evident [E'igure G.6SA and F). fluorescein angiography
shoxvs areas of capillary nonperfusion anterior to the
equator, diEaled relinal vessels and retinal neovasculariza­
tion, and dye leakage into the fibrovascuEar masses and
from relinal capillaries elsewhere [E'igure 6.6^1i).lu,,:,,l° 71-
Angiography of the lemporaE periphery may be helpful in
diagnosing the miEdest form of the disease, ^олст
Three t'iHVR genes have been identified lo dale: N D P
(MEM 30065S, X-tinked), FZD4 [M IM 604579, domi­
nant), and А.КГ5 [M lM 605506, dominant and reces­
sive). l0,--k-,u Linkage analysis in one family suggests a
gene locus either at Xq21.5 or at X p ll. It is of interest lhal
the gene for Nome disease an X-l inked disorder charac­
terized by severe proliferative retinopathy, is also located
at X p il.lu" lhe N D P gene codes for norrin protein that is
also defective in Nome's disease. The gene for autosomal -
dominanl E-'LVK has been mapped lo the Jong arm of chro­
mosome П . ' ^ |м::1 More than 50% ofFEV ft cases do not
carry any of the mutations so far known; hence il is likely
more genes will be identified Id lhe future.
6 .6 B F a m ilia l e * u d a liv e v itre o re tin o p a th y .
Л -F: This S^-year-old molh-er and Я -year-old child had pseu-
doexolrapia caused by Lrmiporal drafy^inj} of lhe m acula in
bolh eyes (A-CI, and F). Visual acuily in the mother was light
perception ir [he right вуЕ and 20/25 in the left eye. The ret­
ina fn rht: ri ц,ЪI eye was totally delacbud by v^'ilow exudates
lli.i. RbrtfVascuEar pttftff-er^tfVe relir^rl сН$ИйФ occurred in
the lemporiii periphery. Fn the ielt eye (C and (here was
fieripheral retinal schisis w ilh inner relinal hoiet !aTrcwsr P .
The sun had temporal draj^jjn^ oP lhe macula, retinal prolif­
erative changes, and lau d a tio n in ’ he te m p o ™ periphery it
and F>. His visual acuity was 2Q/20. Cryotherapy was suc­
cessful in flptHliEraling peripheral retinal vascular abnormal i-
Ljoh The visual function in bulh palienls was unchanged 20
years Lalei.
G -l: This 4-year-old child had fibrovascuiar changes in lhe
infernteiviporal anti inferior periphery of Lhe ri^ht eve i.C and
H and iniurioT periphery of lhe left eye. The left eye in addi­
tion had an ч^ЬпогтаИ у adherttnl vitreous Eiand ex lending
from nasal Iи the dtat .
j and K: Histopalhoio^y of familial exudative vilreoretinopa­
lhy showing funnel-shapMid exudalite retinal detach menl iH
and dense prerelinai vitreous membranes (arrow, Ki (tflng on
lEie inner -surface of a degenerated peripheral retina contain­
ing occluded blood vw seb .
I t ]- 1 ■
: i lur v 11| L i r. F- m n c u A k l e J i I ; ,. I
i fislopathologic examination of eyes with advanced
stages of the disease demonstrates tola! retina! detach­
ment, peripheral reLinal vascular proliferation, exten­
sive prerelinal fibrovascuiar membranes, intraretinal
and sub retinal exudation, and usually iris neovascular­
ization and angle closure glaucoma [t-'igure 6.6SK and
Q-ios+iuiss.i'j^ subretinal hemorrhage occurred
in one case,Л5* and focal inflammation in the regiott
of lhe peripheral fibrovascuiar relinal mass occurred in
ihree eyes.|;'^к|П',с,1]Qiifl ]^e role of inflammation in the
pathogenesis and progression of this disease is uncertain.
Hvidence of ihrombocytopalhy has been found in some,
but nol in other, families. lO S7,m!^-uM6
Unusual fibrovascular proliferation from Lbe retina inlo
the vitreous occurring in late intrauterine life or neonalally
in FtYR is also a feature of Incontinentia pigmenli (see
пел! section), Norrie disease, a congenital X-1inked reces­
sive disorder in males who present either at birth or soon
afterward wilh bilateral blindness and a while relrolental
mass,11"'1 and non familial retinal vascular hypo pi asia asso­
ciated with persistence of the primary vitreous.
]N C O N T IN IL N T IA P IG M E N T I
Incontinentia pigmenli (ttloch-bul/berger syndrome) is
an inherited generalized ectodermal dysplasia thal often
iiiVoLveS the eyes (3 5 % of cases), hair, teeth. And central
nervous system (30% ) [E'igures 6.6У and
Jl is usuaEly inherited as an X-l inked dominant trait
Lhal is lethal In males. Ocular and dermatologic find­
ings of incontinentia pigmenti may occur in mates wilh
Klinefelter karyotype 47,ХХУ of from genelic mos­
a i c i s m . A less common form of the disease (N'aegeli
type] probably has a dominant mode of inheritance,
affects both seres, and is without ocular mill form at ion.1" 1
Incontinenlia pigmenti achromtans is a closely related
syndrome thal also occurs in both sexes (see figure 3.69).
lhe skin, particularly of lhe extremities and trunk in
patients wilh incontinentia pigmentir is involved at birth
or soon afterward wilh bullous, erylhematous lesions
tbal may progress lo the verrucous stage [Figure 6.69A)
and may further progress lo the flal pigmented lesions
that are arranged in whorls and splotches [figure 6.701),
as well as in a linear fashion around the ribcage (nevus
Eines of Blaschko) (I'igure 6.6Ж С, £, and f). The pig­
mentation may fade and disappear in later years. Alopecia.,
nail changes, and dental hypoplasia are frequent {Figures
6.69D and 6.70] I). Central nervous system disorders
incEude seizures, spastic paralysis, mental retardation, and
occasionally rapidly progressing neonalal cerebral isch­
emia.1"''' Ocular abnormalities lhal are frequently Linilat­
eral or asymmetric include strabismus, cataract, myopia,
nystagmus, blue sclera, corneal opacities, conjunctival
pigmentation, diffuse molded pigmenlaiy change in lhe
fundus1" ' {i'igure 6.6!?[■'), patches of chorioretinal atro­
phy. retinal vascular anomalies, peripheral retina! non­
perfusion, p re retinal neovascularization, infantile retinal
detachment, optic atrophy, retinal dysplasia, foveal hypo­
plasia, pseudogtioma (Figure 6.69CJ, and phthisis bulbi.
Progression from only mild relinal involvement neona-
lally to total relinal detachment and blindness may occur
within 3 or A monlhs afler birth.1'"1 ЛЬ normal ilies of lhe
peripheral retinal vasculaLure near the temporaE equator
incEude vascular dilation, arteriovenous anastomosis, pre­
retina] fibrous proEiferation, vascular proliferation, exuda­
tion, and absence of the retinal vessels peripheral to these
changes (Figures 6.6931 and I and 6.70Л-С, |-E.)."r'''
^attachment of the retina
can occur at limes (I’igure 6.70E').111} 'Ihese changes simu-
Eate those in RDF, t-'LVK, sick!e-celE disease, and tales' dis­
ease. Abnormalities of the retinat vessels in the posterior
fundus occur less frequentlyab norm at vascuEature of
the FAZ,IU5jlJLfi dragging of the retinal vessels and hetero­
topia of lhe macula and retinal folds may occur (I'igure
6.69J-I.J. Whereas ihere is a predilection for the retinal
fe.blJ Incontinentia pigmenti
A: Hullo u? and t/errucoUs lesions (]n the fool of a female;
infan: w ilh Lm:onli rienlia pljrijienti.
S: Linear ад япцвгП йт of blgrnwiied nkin lenionn around lhe
rib cajje (nevus lines ol" Bla$£hfco).
(. and D: Pseudogfftirtia in lhe rij^hl eye and bigfntwiled skirt
Eesicm in the armpit of [his ID-year-old f>irl w h o had denial
hypoplasia (D L
E—G : Blotchy pijjm enlalion ol lhe 3egs and fundi in a young
l^iil w ilh optic dif-c anomalies.. peculiar r^idi^itiп_ц lines or
fold*, and subrelinal lesions in lhe m acular areas it. I..
H and 1: Angiogram (H) show ing peripheral retinal vascu­
lar proliferation and shunts :h-E* posterior edge ol lhe io n e
or relinal vascular n o npeil'u-siо n Erel'one photoLoajjulaLion.
Composite fundus photograph (I] shotws ь л т е area a i l e
pholooria^u hit ion.
J-L: Inianl girl w ilh typical pigmented lesions around lhe
Irunfc Ц'1, dragging of lhe macula (a maw, К and L . and a reLi-
nal fold. CryoLherapy was u w d Lo [teal proliferative relinal
vascular changes (not shown] in lhe peripheral fundus, ih e
was delivered afler a fuK-lerrn pregnancy and did nol receive
ни pplementa I oxygen a fler dn I ivory.
IT-,iivI (j, fr-uni ,Vk(..'r,iry- ;md Smlfii1'' I ^641, Апшпс/мп iVttdk ;il
As4* uJidh All r^hls н.'чипл'с! I'E niritf 1. Irum Nislrmui.i L’l
vascular changes to involve the periphery, the posterior
pole may be affected by similar BpqLdj&0Lgs.jOW' m i-LO:17,!}
Patchy variegated and whorl-like pigmentary changes in
the fundus, similar to those of (he skin, mav occur (Figure
6ЯЭР)
L'he palhogenesis of lhe fundus changes is uncertain;
lhe similarity of the pathology' lo KOP suggests a congeni­
tal defect in the development of lhe retinal vasculature. On
lhe other hand, lhe retinal vascular and nbroproliferative
changes may be secondary lo a primary abnormality of the
RPE. ]"1~> Nisliimura and associatesIL:'" observed the pro­
gressive development of avascular areas in the peripheral
relina of a full-term newborn during Lhe first month and
a half of Eife (llgure 6.69 El and I), ill is was much more
severe in one eye than in the other and was accompanied
by ischemia, a cherry-red spot, and optic atrophy in the
more severely affected eye. 'Ihey believed Lhat proliferative
retinopathy Was caused by progressive postnataE vascular
obstruction and postulated (hat the circulatory impair­
ment may also involve the choroid, optic nerve, and other
tissues in the body. A similar case of fiftrente relinal avas-
cularity with vasculature limited lo approximately 1.3 disc
diameters on either side of Lhe oplic disc has been noted
in Lhe left eye of a 26-day-old infant by Meal Eel et at.1" '
and in a newborn by Chao et al.111'' iome aulhors have
demonstrated what they interpreted as a favorable effect of
pholocoagutalion and cryotherapy in the treatment of pro­
liferative retinopathy (Figure 6.69H and lyura.nflJ.JUB.ius
Other authors have reported less favorable resulls.1141
Ijicttn J/pfejK{jLT 5/9
 Mutations in lhe inhibitor o f kappa Sight poly peptide
gene enhancer En К cells., kinase gamma. IH JftC (Gen Han к
ISM_003639.3; M IM # 30 024 8 ) Л Iso called nuclear factor
kappa II (N F -кЖ essential moduli! to г (N tA I oflKKgpm m a}
at the Xq28 location, is responsible for incontinentia pig-
menli in about 8 0 % of p a t i e n t s . M u t a t i o n in this gene
Leads Lo activation o f eotaxin, an eosinophil chemokine.
Accumulation o f eosinophils in tissue, and in or around
blood vesselsv results in skin vesicles and vaso-occlusive
findings in lhe eye and brain.1 1' The mutation may occur
de novo or may be tracism tiled in an \-\inked dominant
fashion.
b.7L) incontinentia pigmenli.
A —I: lbih 40-yoar-old youngest of five siblings with no Family
history ot eye <jt sysletnlt disease was found Lo have )з.гн;И#Й-
lous vessels in the righl five ;.A \ She was в ггкик!та1е myope
w ilh corrected vision to 2Q/20 in each eye. lh e temporal and
inferoLemporal retina showed peripheral nonperfusion w ilh
pigmentary changes suggesting sponlaneous ^ U a d y n m l
of a detached retina (E-D ). Angiogram confirmed peripheral
avascularily (Ё and FK Гlie left fundus had a normal vascular
pattern. She had small vitiliginous patches on her skin simi-
l.ir Lo Ьем falhcr. N ail .H and skin changes or" inconl inentia
pigmenLL w ere seen over her forearms and Lhighs lb. She gave
и Liislory o f having bliiLers over he* L>ody and scalp as a neo-
natn. Two older brolhers and sislers and m olta1? w ere Unaf­
fected. indicating the possibility ol de novo mutation in her.
J-L: Thi н 5 2-year-old white female prosonLed with vilitegus
hemorrhage in Lhe 1еЙ eye. She had a past history ol viLre-
ous ЬёйтОггИада in Lhe right eye requiring laser photocodgLl-
lalion approximately 6 years; previously. The posLcrior pole
was normal. The lemporal periphery showed laser scars w ill:
sheathing of the relinal vessels and absent vessels anterior lo
the laser scar. Far periphery of lhe lefl eye showed periph­
eraL nonperfusion and ghost-like proliferative vessels, some
inlraretinally and ногтч1 growing inLo vilreous at I Lie junction
of Lhe perfused and nonperfused retina (J and KJ. Fluorescein
angiogram of the periphery showed dilated collaterals and
capillary lied corresponding Lo Ihe gbosldike vessels seen on
lhe color photographs lj. The relinal vessels were shon in
other areas o f the periphery. She had skin lesions Lypical of
inconlinenLia pigmenti w ilh whorl-like defecls.
U—L. t.[jurt*iy nt Ur 'iVMi.nn Mjl'Ilt.!
Dystrog[ycanopathies (Muscle-Eye-Brain
Disease)
Dystroglycanopalhies are л ^roQP Ф 7genetic disorder jthat
involve bolh centra! (brain and eye) nnd peripheral ner­
vous system (skeletal muscle) caused by underglycosylation
o f djijpha-dv'stioglycaft. with O-!inked c;irbohydraLes. Alpha-
dystroglycan es а 156-k3.>a peripheral transmembrane
protein th at undergoes multiple glycosylation sleps lo
Lnteracl with extracellular matrix proteins such a& laminin,
neurexin, and perlpqan.113-1 So far, mutations in six differ­
ent genes - J f c m № \ IT 2 , P O M G n ti' fukutin (Г К Г Х ).
FK R P ; and I.ARtrt' - Ilave been recognised..1 ihere is con­
sider able phenotypic variation in lhe clinical syndromes
with a wide spectrum of clinical findings ш each - Walker-
Warburg syndrme, muscle-eye-brain disease, Fukuyama
congenital muscular dystrophy, congenita! muscular dys­
trophy types ID and 1 Cf and limb girdle muscular dystro­
phy variants, LpM D 2I, I.GMD 2E.. and ^ M D 2N .lt24
The clinical findings of hypotonia, muscle weakness,
contractures, seizures, hyporeflexia. and menial relarda-
Lion coupled with elevated serum creatine kinase activ­
ity guide lhe diagnosis of dystroglycanopalhy. The group
of disorders is characterized by variable involvement and
severity of cerebraE cobbles lone lissencephaly (agyria,
pachygyriar or polymicjogyria}, cerebellar, pons or brain­
stem hypoplasia, absent corpus callosum, hydrocephaly,
muscular dystrophy, eye involvement including myopia,
retinal delachment, abnormal retinal vasculalure, anterior-
ehamt>er abnormalities. microphthalmia, and persistent
hyaloid sys lem
fc.7 E Mu sc Ie-eve—brain 1.1ЧЛЕВ) disease,
A -F: This 2-rticjnlh-cild presdrrted w ilh puur fixation in bolh
eyes and was found L(] have rn^tpiibbflrarnia and retinal
detatfiriti^flt in 1h-u right eye and aljnormal iDveal imJ&k in lhe
left eye. She wan born at full term liy £^Кэгвап нес Iion, .ind
was rioted lo have hip dysplasia. th ere were no s-kiгь lesions,
tiompuled lom oyraphv scan showed enlarged laleral ven ­
tricles and thin corpus taLlusum. lh e rij]hl retina wa.^ dys-
plasUc will* peripheral a vascularity in Lhe superior Quadrant
and exudative rh in al delachinent iA and B '. The lefl reLrna
was also iiypoplasLic but fillached Ci. A fluorescein an^io-
цгат bf lhe ri^ht eve confirmed Lhe peripheral nunperfusion
on lhe riuliL and anom alous vascular pattern in Lhe left \L5-h .
Ftillhef delay in milestones, hypotonia, floppy musc3esr nnd
elevaled creatine kinase IС!K) levels prompted leslin^ for
ME;hi disease lhal returned positive for heterozygous nv.Ha-
tion in F Q M G n T I f^ene. lhe- exudative relinal detachmunl ir>
the rif^ht eye sell led oveT 1 years-, leaving a fold in Lhe pos­
terior pokh in пег righl eye. The lelt eye underwent periph-
eraE scatLer ablation lo areas o f nonpedusion. Bath retinas
remained unt handed at a^e 4.
ш П Й у ol IJr. НлпЬй R c L -c t i -f i .l
Muscle-eye-brain [P ^ M C n T l] has more ocular involve­
ment involving both anterior and posterior segments,
including microphthalmos, glaucoma, myopia, coloboma.
secondary cataracts, retinal hypoplasia resulting in periph­
eral avascu!artly similar to ROP (I'igure 6.7115 and t), exu­
dative (I'igure 6.71Л and В ) or secondary7tractional retinal
detachment and optic nerve hypoplasia,1135']1261UJ9-L]iJ
Ъ ^ о п ф ка Ил piem en fi 5й-3
D Y S K E R A T O S IS C O N G E N IT A
Dyskeratosis congenita is a m иI Lisystein disorder that is
caused by defects in lelomere maintenance. Telomeres are
com pie* DNA protein structures lhat protect chromosome
ends from degradation and inappropriate recombination.
Jelomeres shorten wilh each cell division, -and when they
become critically short a D KA damage response is acti­
vated, causing cell cycle arrest and cell death. She]letin,
a complex of sis proteins, binds to lelomeric DNA and
protects it. Telomerase enzyme synthesizes le loin eric
repeal sequences on to lelomere ends. Et is inherited as an
autosomal-dominant, X-l inked recessive, or sporadically
by de novo gene mutations, in the X-l inked form, muta­
tion occurs at the Xq2S locus, resulting in dysfunction of
dyskerin, a protein in lhe telomerase complex.1,31 '['he
dominant form is caused by mutations in the о Lher com­
ponents of the enzyme telomerase. such as the telomerase
RNA, TERC, and a reverse transcriptase TTiRT1154
Гоог lelomere function affects cells wilh high turnover
such as the epithelium, bone marrow; skin, and nails,
resulting in multisystem manifestation. The disease was
first described with a Iriad affecting nails, skin pigmenta­
tion, and mucosa] leukoplakia more lhan Ш0 years ago.
Hone marrow failure, premature aging, pulmonary fibrosis,
and malignancy are serious manifestations. Pancytopenia,
short, ridged fingernails, and patchy skin hypopigmenta-
Lion are hallmarks of this condition. Ocular findings may
include epiphora due lo tear duct obstruction, dilated con­
junctival blood vessels, corneal limbal stem cell failure,
corneal vasculopathy, dry eyes, conjunctivitis, blepharitis,
loss of eyelashes, microphthalmia, strabismus, and cata­
ract.1' " Retinal changes are rare but can include retinal
hemorrhages, nerve fiber layer infarction, narrowing of
the retinal vessels, prerelinal fibrosis, and oplic atrophy.
Ketinal vasculopalhy in the form of aneurysm forma­
tion with leakage resembling Coats' disease is seen.111'
Occasionally, progressive peripheral vaso-occlusive reti­
nopathy occurs (Figure 6.72)." "
Other systemic features lhat have been recognized
include premature graying of hair, premature tooth loss,
en tenopathy wilh т а Iabsorption, immune deficiency.
b. 72 Dys kera losis со nge nitn .
A -L: А 20-year-old m ;i It? was 1he pf oband w il h 2 0/20
vision in the righl eye and 2 0 / 2 0 0 in [he left eye. He was
known to have interstitial lung disease, and had a biopsy of
his lunyr liver, and Iw ne ttiarrow, Min f,Uheir's diagnosis was
esLaIjIinhed 10 years previously and a sisLer had died in htir
early 20s from renaE faiГиге. His platelet counL was I S 000
Lells/^tt. total w hile count 2500 ceEls^l, hemoglobin 13.1ц/
dl, with elevated liver enzymes and bilirubin. H-lood urea
nitrogen and creatinine w ere normal. The ri^bL fundus was
normal: lulan^ieclatic dhafltaes w ere seeflj in Ihe left rnaculS
(A and И).. In addition Lo dilaLed and leaking capilEaries and
aneurysms in Ihe iefl macula, artgfogram showed peripheral
nonperfusion which was worse on Lhe leil compared to lhe
ri^ht, and mild toveal capillary leakage on (he right fC-G).
The left fovea was thickened on optical coherence lomoj;-
raphv. M iн 47-yeaf-old fa Lher had 20/20 vision in bfllh eyes,
and showed mild foveal Lelan^ieclasia fl and J1 LhaL leaked
very m inim ally on Lhe angiogram ik and 1Л H e had pulm o­
nary fibrosis and peripheral edema. Another tislef and Lwo
nieces ot" lhe pmEjand were also posilive, in addition to Lho
proband and his lather, for Lho !ЬКС. gene mutation. The
family clearly depicts genetic anticipation; Lhe falhter was
less severely affected compared 1o lhe коп iprobandi and a
daughter w h o died in her early 20s.
il- ш т kthrjsr:,n c l j | . wdlh репт1Ещпгт, A, 15. t. i ■:I (.!, A b u , n n n u i i i ,
L .m r c m и J .. l l i u K u Ijn . j I А Й * £ b .iu rid i’ n 1(11 0, 9 7 Л - П - 7 (Ц ()- 3 .!2 0 - И ,
MS.L
esophageal slriclure, cardiomyopathy, fiver cirrhosis,
osteoporosis, and avascular necrosis of the bone. urinary
tract abnormalities, testicular atrophy, mental retardation,
intracranial calcifications, and cerebellar hypoplasia with
ataxia. They have a predisposition to develop malignan­
cies such as secondary acute myeloid Leukemia, myelo­
dysplasia, head and neck cancers, and esophageal cancers.
Wore lhan one cancer may occur in an individual.11^ !^!J
All features are nol preseLit in childhood; many develop
over Li m e.
'Lhe Nobet Prize in medicine was awarded to tlizabeth
H. Blackburn, Carol W. Greider, and ]ack W. Szostak in
2009 for the discovery of how chromosomes are protected
by telomeres and the enzyme telomerase.

R ET IN A L V E N O U S O B S T R U C T IV E
D IS E A S E S
In lhe end-artery vascular system found in lhe retina,
obstruction оГ a retinal vein causes elevation of lhe wnous
and LntracapilEaiy pressure and a slowing of arterial blood
flow in the area drained by lhe vein. 'lhe visual defects and
retinal damage produced by venous obstruction depend
primarily on the rapidity of its development, lhe degree of
obstruction, and lhe availability of collateral pathways of
venous outflow, if lhe degree of obstruction is mild, capil­
lary endothelial damage is minimal and leakage of serous
exudation and exlra\rasation of try throcytes into the retina
may be unassociated With significant ischemic damage to
Lhe relina (Figures 6.7 ЗА and 6.74A-D). Complete resolu­
tion of lhe fundus changes and return of retinal function
may occur following venous recanalizalion and (he estab­
lish menl of collateral venous channels.k With moder­
ate venous obstruction, Lhe decree of retinal hemorrhage,
exudation, and ischemia is greater, E'ollowing restoration
of normal venous pressure, the retina may remain edema­
tous secondary to prolonged or permanent damage to [he
retinal capillary endoLbelium (secondary retinal telangiec­
tasis). if the degree of venous obstruction is great, hemor­
rhagic infarction of the relina causes extensive loss of the
retina] capillary bed and postischemic cysloid degenera­
tive and atrophic changes that remain after restoration of
6.73 H is to p a th o lo g y o f re tin a l vein o b stru ct io n.
A: V iild venous obstiucLitMi with intfaneti na I UKEMvasation
ot etyihtocytes ;ind m-нiп I en-ia nee ot" i d л lively normal relinal
architecture in a hypertensive palienl With evidence (if arte-
i i о Is r sdujosi я ■arnrm .
i?: Severe venous obtLruclion with hemorrhagic i шГл rc: Li on of
Lhe inner ralina.
: CysLic degeneration ot the relina many lYionlhs afler
severe ven ou?- obsLruc Li o n .
D : Cystic degeneration ol Lhe reiina and m acular hole Гснтла-
Lion after нечего central relinal vein a te I us ion.
E: M acu la r schisis, exudative refi поражу, retinal degen­
eration, and epiretinal т ш п Ь м п и and pucker secondary lo
severe central retinal vein occlusion and rubeotfc glaucoma.
NoLo Lhe lipid-laden ftiacrophages i.nrrcnvi in Henle's layer.
normal venous pressure (Figures 6.73 E3—L> and 6.74G-L).
The presence of retinal arterial insufficiency enhances the
likelihood of venous obstruction and increases the retina]
datnage caused by the venous obstruct ion. lliere is little
clinical or experimental evidence, however, to support
the viexv that some degree of arterial insufficiency is nec­
essary for venous obstruction to produce retinal hemor­
rhages. 1,1" !- 11 ■" Jhcre is color Doppler imaging evidence
lo suggest that diffuse smal[-vessel disease and reduced
blood velocity may be important in the pathogenesis of
central retinal vein obstruction in some patients. ■I'J|>LI 4
C E N T R A L R ET IN A L V E N O U S 6.74 Central retinal vein obstruction.

O B S T R U C T IO N A—F: M oderately severe central relinal vein obstruction in

lhe left eye E3' of а 4.2-year-old black wom an w ilh slfckHe-ceft
Various terms have been used lo describe Lhe severity of Ira it. Visual acuity was 2 0 / 2 0 in lhe rigjil eye (A) and was fin­
retinopathy associated wilh central relinal venous obstruc­ der co'.i riling in I Fie left eye IK). Bulb oplic disLS were sli^hlly
pale. Angiography demonstrated evidence o f prolonged reti­
tion (Figures (i.73 and 6.74).11 ,:-1" " None is completely
nal cirvuIaLiun lime and diffuse dye leakage from Lhe relinal
satisfactory. '['he clinical terms used lo describe lhe ocu- capillaries, venules, and veins (Cl. Two years later the patient
Ear fundus reflect the degree of obstruction of Lhe entire relumed because u1 binned vision secondary to impending
venous outflow from lhe relina [central retinal vein plus cenlral reHlnal vein ofaslrudiqii in I be riftht eye <Ш- Nole the
eollaleral vesselsJ and not jusl lhe centra! relinal vein dilated venous collateral vessel on the optic disc (arrows
alone. A palienL may have complete anatomic obstruc­ lh e leA fundus was normal ■:£). Visual acu ily was 20 /15 in
tion of the centraE relinal vein at the level of the Eamina lhe rijjfil eye and 2Q/21) in lhe left eye. Two months laler lhe
relinal hemorrhage* bad cleared I-ir however, a few m icro­
cribrosa. with we 11-developed collateral ven out Йг^ЬпеЦ,
aneurysms remained. Visual acuiLy was 20/Sjffl bilaterally and
and manifest only minimal fundoscopic changes of has remained so for 7 years, despiLe recurrent vilneouj; hem-
venous occlusion. onhaLjes secondary lo peripheral areas o f neLinilis probrer-
ans and retinal vessel nonperfusion identical lo thaE seen in
Impending, incipient, Partial, or sickle-cell hemoglobin С disease.
G —|: M oderately severe nonischem ic central retinal vein
Incomplete Central Retinal Vein Dc-dlision and optic disc edema f(J . Angiography rtvE H e d
Obstruction an increased retinal circulation time and inlraretinal sLa in-
in^ ■:t-E and I). Note ioi lowing spo n I aneou s resolliLion af lhe
Jhese terms л re used synonymously lo describe the fundi obstruction iho venous eollaleral vessel (arrow, 3) on lhe
of patients who are either a s y m p to m a tic or who may optic disc and lhe reLinai [jit>menl epithelium atrophy con­
complain of mild, ofLen transient episodes of blurring of tra llv caused by dissection of inlra retinal blood inlo 1he sub-
vision. 1heir fundi demonstrate mild venous dilation, a retinal space during lhe acule phase pf the disorder.
few widely scattered retinal hemorrhages ( I'igure 6.74D), К and L: ie v e re Central relinal vein obsIm c lion. Nole the
pallor o f (he optic disc, colton-wool patches, diffuse isch­
and a mild increase in relinal circulation lime angio-
em ic w hitening of (he reflina, and multiple retinal hemor­
graphicallyl]5l1lM The term "venous stasis ielinopathyD
rhages K.I. Angiography revealed massive dmp-oul oi lhe rel­
to describe these patients probably should he avo id ed , inal capillary bed ■;Lj.
since it was originally used in Lhe literature lo describe
focal retinal hemorrhages scattered in the peripheral fundi
in patients wilh reduced retinal artery pressure caused by
hemorrhages; marked swelling and obscuration of the
carotid artery obstruction.
optic disc margins; multiple focal zones of ischemic u'bit-
ening; colton-wool patches; diffuse loss of relinal transpar­
Nonischemic Central Retinal Vein ency; marked Increase in lhe central retinal vein pressure
Obstruction (Perfused Central Retinal as determined by an inability to collapse Lbe relinal vein
Vein Occlusion! with digital pressure;1 angiographic evidence of marked
increase in retinal circulation time; evidence of Earge
Mi id to moderate loss of acuity usually 20/200 or better; iones of capillary nonperfusion; severe capillary perme­
widespread retinal hemorrhages; angiographic evidence ability alterations; and severe alterations in the eleclroret-
of mild lo moderate cysloid relinal and optic disc edema; inogram (Figure 6.74К and Lj.-ir: The term "combined
minima] or no areas of capillary nonperfusionr and an central retinal artery and v ein obstruction" may be war­
increase in relinal circulation lime characterize these ranted in patients with severe visual Eo&s and extensive
pa lien is (Figures 6.74K-, Cr and С -I, and 6.7!>А-С). Hlood ischemic whitening of th e reLina as well as scatLered reti­
Levels are often seen within the large retinal cysts in the na! hemorrhages. L'hese palients are more Likely Lo have
foveolar area.L s fbo me cotton-wool patches, particularly in evidence of ophthalmic or carotid artery insufficiency
Liypertensive patients, may be present Transient retinal ves­ Patients initially exhibiting one of the lesser degrees of
sel wall sheathing may occur.'1" lhe intraocular pressure obstruction may subsequently develop a more severe
in the affected eye is often lower lhan in the fellow eye.1" 0 form of obstruction.11111''11''- A limed fluorescein angio­
graphic study, preferably using a wide-angle fundus cam­
Severe (Ischemic) Central Retinal Vein era. can document the degree of obstruction, the severity
Obstruction (Nonperfused Centra] of the capillary permeability alterations, and after partial
resolution of the intrarelinal hemorrhages the extent of
Retinal Vein Occlusion]
lhe retinal capillary nonperfusion (Figure 6.74К and L).
Patients with severe central retinal vein obstruction typi­ ll is important lo include views of the peripheral fun­
cally have severe visual Loss- usually less than 20,'200; an dus and the posterior pole, since capillary nonperfusion
afferent pupillary defect; widespread confluent relinal is most likely lo occur in ihese areas. In the presence of
widespread сил fluent hemorrhages, El may not be pos­
sible lo determine angiographically the extent of capillary
closure.1 1 Lite staining along the large relinal veins is a
characteristic finding in moderate and severe degrees of
central retina] vein obstruction (figure 6.741). Jhe ctini-
caE findings of visual acuily of Less than 20/200r an affer­
ent pupillary defect, marked intraretinal hemorrhage with
Loss of retina] transparency, and inability lo collapse the
central retinal vein with finger pressure are adequate lo
make an accurate diagnosis of an ischemic-type central
retina] vein occlusion.1' : L]'' Ancillary tests including
fluorescein angiography and eleclroretinography are rarelv
necessary. i]^ il?i-il??-:i7f;:
Unusual changes lhat may accompany central relinal
vein obstruct toil include shallowing of lhe anterior cham­
ber. " IJ angle closure glaucoma.!_ " malignant glaucoma
following a glaucoma filtering procedure,"liL exudative
retina] detachment.L]63rL] 6J and cilicreiinal artery o c c a ­
sion.>ЛьVery rarely, ongoing vascular remodeling can occur
for yeari after a central retinal vein occlusion, resulting
in telangiectasis and formation of collaterals leading lo a
Coafjs'-type response (llgure 6.7G],
The natural course of this disorder is variable and
in large measure correlates wilh lhe degree of obstruc­
tion evident initially, the location of the occlusion in
the course of the vein, and the length of occluded seg­
ment of the vein ."64'118*-11*6 Some palienls with mild
to moderate obstruction may show complete recovery of
vision and restoration of the fundus to normal with in a
matter of months (I'igure 6.74A-F) from restoration of
lbe flow wilh in the vein. Others show slower resolution
of die retinal changes and incomplete visual recovery.
Some develop evidence of prominent venous and collat­
eral channels on lhe op lie nerve head that shunt blood
through the choroidal circulation and thus decompress
the congested vasculature [Figures 6.74D).M'1' Progression
from the nonischemic to lhe ischemic form of central reti­
nal vein obstruction occurs in approximately I d— of
older patients and 5-lQMi of patients less than 65 years
of a g e . A f t e r resolution of all relinal hemorrhages and
Venous engorgement, varying degrees of permanent retinal
capillary dilation, capillary loss, and permeability altera­
tion may remain in the macular area (figures 6.74]).
Permanent macular changes include СМИ with or
without evidence of cystic degeneration {i'igure 6.75C,
L and b')f an inner lamellar macular hole, a full-thick ness
macular holer epi retinal membrane change, RPE atro­
phy. and proliferation caused by dissection of blood
beneath the retina during the acute phase of the disease
(figure 6.74]).. arid traction detachmenl of the macula.
6.7j Central retinal vein о bslruction.
A—С : Chronic cystoid macular edema IB and C) remaining
us the o nly siyn o f л previous cefttral relinal w in occlusion
IA' lhat occurred 12 months previou^v.
D -F: In 196a this patienl had a moderately severe central
relinal vein obstruction in the lefl eye (D). AIL of [he reti­
nal hemorrhages cleared but his visual acu ily remained a I
10/200 because of с h remit cysloid mac a Ini degeneration
and edema until 19-71 IE In the Eate anjjio^ram was a l.irec
irregularly shaped cenlral cyst indicalive of" permanent dam­
age lo lhe foveal relina Inol shown'. Al lh al time si\ appli­
cations [jf setiOfi phoLocoa^ulalion w ere placed in lhe area
□f lhe relinal arlu-nes supplying Lhe m acular area. Six months
later Lhe cysLoid m acular edem a had resolved, bul i here was
no improvumenl rn visual acuity (F).
С and H : O ccu lt central relinal vein occlusion occurred dur­
ing the course of follow-up of 1hiн patienl at yearly intervals
because of idiopathic central serous retinopalhy in the Mghl
eye. Note the development o f numerous small venous co l­
laterals on lhe optic disc ol the left eye that occurred over a
1-year interval in lhe absence o f any symploms or other e v i­
dence of venous obstruction.
I—K: This 48-year-old African Am erican oLherwise healthy
wom an presenled w ilh headache and visual b urring of her
Eeft eye. Fttalloid-shaped deep outer plexiiorm layer hem­
orrhage and some while-cunlored hemorrhages prompted a
head computed lomography lo rule oul subarachnoid hem­
orrhage and blood dyscrasiaF- causing anem ia ilj. Angiogram
revealed good relinal pertu-sion. O ther Lhan being on oral
contraceptives, no olher risk factor was detected, ih e pro­
gressed to a central retina I veirl occlusion wiLh d ia le d and
tortuous relinal veins, increase in number and extent of reLi-
nal h em o rrh age i1f1^ collon-wool spols. and a decline in
vision Lo 20/2Q0 2 weeks later. W ilh in T2 weeks she devel­
oped iris nuovasculaTizalion requiring panrelin.il pholo-
coa^ulation. Thu iris vessels regressed and her intraocular
pressure rem.iinrtd Linder 21 mm Н у with lopical medical ions.
Her vision remained al 2 0/200.
lo r uncertain reasons, proliferative retinopathy occurs
less frequently after centra] lhan after branch relinal vein
occlusion.-111" Probably fewer than of palienls
with central retinal vein occlusion will develop evidence of
iris neovascularization and hemorrhagic glaucoma, Ihis
severe complication is most likely to develop within 3-4
month5 in those palienls who have the severe ischemic
forms of the disorder.L]e^l]90itie risk of developing neo­
vascularization is less in patienLs with a posterior vitre­
ous separation.1'"! l he risk of developing a cenlral retinal
w in occEusion in the second eye is approximately lO-lS^o
and is more likely to occur if the paLient is diabetic or has
some other associated systemic disorder such as polycythe­
mia or macrogtobulinemia.l|,>i
 lhe visual I prognosis in palients below the age of
50 years is belter than in older patients [F L m f 6.74A-
K).'■E:' ||Й*-||Й-1|М leaner of the younger patienls show (he
severe acule phase of obsL ruction. and a high percentage of
younger palients with all stages of the disease show greater
degrees of visual iecotfery.110'1 Lhe term "'papilloptilebi-
Lts" is used by some authors to describe the incipient and
mild to moderate degrees of centra] relinal vein occlusion
in younger patients, particularly in paLients with promi­
nent optic disc swelling and with retinal hemorrhages
la te ly confined to lhe posterior fundus." 1'■|: ,fl Some
patients wilh papillophlebiLis may manifest evidence of
partial obstruction of the cenlral or branch retinal artery
and optic disc ischemia as well (I'igure 6.77A-Ei, and
H ).3i&rL]S? in younger patients venous obstruction is prob­
ably caused primarily by disorders producing oplic nerve
and disc swelling wilh secondary venous compression.,
rather lhan a primary venous thrombosis occurring al lhe
Eevel of the lamina cribrosa, as is usually the case in older
palients {Figures 6.76 and 6.77F-J). in т о м palients with
papilEophlebitis there is no associated systemic disease
and there are no inflammatory cells in the vilreous near
the oplic nerve head. In a few patienls il may be associ­
ated wilh oLher disorders including pregnancy, use of birth
control medications, oplic neuritis, and ulcerative coli-
^ _iiss,lhmu(M Although young, otherwise heallhy adults
with central retinal vein obstruction have a more favor­
able prognosis than older patienls, as many as one-third of
those referred lo retir'd specialists miiy have a final visual
acuity of 20/200 or worse.L-IJI'
Ijtperimental production of the clinical picture of a cen­
tral retinal vein occlusion in animals is difficult because
of the avahabilily of collateral pathways of venous out­
flow near the optic nerve head."1■!--IN LI" ■j-iimopalhologic
studies in humans have demonstrated a thrombosis occur­
ring al the level of, or posterior lo, the lamina cribrosa.1"'1
It is likely the thrombus is a secondary event due lo sludg­
ing proximal to the site of occlusion, lhe greater likeli­
hood of associated central relinal arterial disease in older
palients may explain Why they have a poorer visual prog­
nosis than young patients.
Allhough some patients have factors predisposing them
Lo cenlral relinal vein occlusion, such as glaucoma, diabe­
tes mellilus, hypertension, polycythemia, sickle-cell trail
(E'igure G.74A-L), Reye's. syndrome, inayamoya syndrome,
homoeysleineniia, dysproleinemias, carolid artery insuf­
ficiency, carotid cavernous fistula, and use of oral contra­
ceptives. amphetamine, cocaine, phenyl propanol amine,
and Lranexamic acid, most have no recognizable cause
for developing venous th ron ^ osi*** 2fi0'3 £ ] ]
Mansour el a I., followed 78 patients for 2 years or more
and found no increased risk of mortality or morbidity. '■ '
Retinal venous obstruction occasionally may occur fol­
lowing accidental trauma, surgical trauma, such as repair
of a blowout fracture or scleral buckling procedure, isch­
emic oplic neuropathy, papillitis, papilledema, cilioretinal
and branch retinal a rtery occlusion, congenital anomalies
(j.7t Sequelae of central retinal vein occlusion with
Coais'-like response.
A —L: This 1 7 -■jujir-uld A ft1Can Am erican т л и noEed a uudden
Foss o f vision in his lefl eye associated with severe headache
Lh;tL lasled only miiuiles. He was found ta h a w sectoral deep
relinal wbi Lenin ед associated w ilh sevafal blot retinal hem­
orrhages :Al. Anj'iojjram revealed .щ т с delay in Lhe arrtj lo
rcliiTEiAjhtNoid lime МЙ sec-dtitbj (B and Cl. hi is vision was
20/25 w hen seen, w hich was 7 days alter his symploms
A:i : -i! ? : i! -: n iv.il .u- t ii\ 11-.:: ■
■■i: v. ,ь - - i i f : ii:
ihis otherwise healthy man. E3Г-cjod work, orbital and head
magnetic resonance imaging revealed no abntjnmaIiIies. The
whitening and hemorrhages; had improved в days lairs IDJ.
H iы blood pressure was m ildly elevated and he was starled
on medications. SEh weeks later he returned w ilh no new
symptoms and a vision o f 20/20 in both eyes. He n o w had
venous toTtuosily, and several retinal hemorrhages in all
four quadrants consislenl w ilh a central relinal vei:n o cclu ­
sion (E-C ). His central vision dropped to 20/40 over the next
monLh secondary Eo cystoid m acular edema. Coagulation
nUrries and (.-.irdvu workup i ivi-iilo: nr :■ .ibnormaiilies:
he was monitored. A year ialer his vision had improved lo
20/25r most of lhe hemorrhages had resolved iH and IK and
lhe cysts in the fovea hnid decreased, hie was found lo have
peripheraJ lipid in the mferu nasal and temporal periphery 3
yvars later that gradual Iу increased. An angiogram revealed
dilated capiElary bed in the adjoining areas and microaneu-
rvsm formal ion ■;К and L) simulating CoaLs' response. C iven
the 20/20 vision and the peripheral location o f Lhe exudales,
he was monitored and grad’ja ily lh e lipid decreased over the
nexl 3 уеагъ.
of the oplic disc, drusen of the oplic nerve head, and
B'regnanCJt/195jll9^Lsa2-tlj!!i O ilier factors incriminaLed
in venous thrombosis include abnormal blood viscos-
ityr1^ - 1223 elevated erythrocyte aggregaLion,1-i-"'and lipo­
protein and plaletel abnormalities. I-W5_'123- Although
patients with glaucoma are al increased risk of venous
obstruction, i:"-A oplic disc size and oplic cup disc ratio in
fellow eyes of patients wilh venous obstruction are no dif­
ferent lhan that seen in normal e y e s . Likewise,
congenitally lilted oplic nerve heads do nol appear lo be a
risk factor for central retinal vein occlusion. ^ Although
some have found evidence lo suggest a seasonal variation
in lhe onset of central retinal vein obstruction, others have
n(>lL2ММЮ
lhe re is no convincing evidence of medical treatment
favorably altering the natural course of central relinal vein
occlusion. Pilot studies have suggested that oral iroxerulin.
an inhibitor of platelet and erythrocyte aggregation, and
hemodilution treatment lo lower blood viscosity in ay be
of some bene fit.] J Jij' 4: Intravenous admin islralioti
of streptokinase appeared lo reduce the morbidity but has
never gained favor because of the risk of intravitreal hem­
orrhage. i : ij lhe value of systemic steroids in Lhe treatment
of young patients with central retinal vein obstruction
wilh the presumption that it is caused by a "papillophle-
bitis'T is uncertain, since mosl young patienls have a favor­
able course without treatment.
 The results o f Lhe Central Vein Occlusion. Study con­
cerning lhe Value оГ early prophylactic ГК11 treatment in
patients wilh ischemic-type сел Ira I relinal vein occlusion
in preventing iris neovascularization demonstrated (haL
prophylactic treatment does not totally prevent im and
angle neovascularization, and that prompt regression of
iris and angle neovascularization in response to PFEF is
more likely to occur in eyes that have not been treated pre­
viously.Ijl 41'I hey identified four risk factors for developing
iris and angle neovascularization: (1) extent of nonperfu­
sion on fluorescein angiography (2) large amounts of reti­
nal hemorrhage; (3) short duration of cenLral retinal vein
occlusion; and (4J male sex. Jf adequate fluorescein angi­
ography cannot he done because ot" hazy media or because
o f extensile in Ira retinal hemorrhage, eyes should be fol­
lowed as if they had an ischemic vein occlusion.1' J1 |Лм
]Ъе sludy found no apparent benefit in performing []RP
before development of iris and angle neovascularization.,
provided frequent follow-up examinations can be per­
formed. Since 20% of early trealcd patients later devel­
oped iris and angje neovascularization, frequent follow-up
is necessary following PRP. lhe study group recommended
careful observation o f all patients with recent central reti­
nal vein occlusion with frequent (approximately monthly)
follow-up examinations for 6-fl months (including undi­
lated slit-1 amp examination o f the iris and gonioscopy)
and prompt P R ET of eyes in which iris and angle neovascu­
larization develops, it is important lo follow patients with
nonischemic central relinal vein occlusion since the sludy
found thal, with in 4 months, 10% o f cases of nonisch­
emic patients progressed to ischemic central relinal vein
occlusion.
The use of scatter treatment for CMti caused by cen­
tral retinal vein occlusion was evaluated by lhe Central
IJelinal Vein Occlusion Study, which found the treat­
ment ineffective in preserving or improving cenlral visual
acuity.-"""1-1'1' 'lhe SCORE: study found that use o f I mg
and 4 mg of triamcinolone lo improve visual Loss from
macular edema in patients with central relinal ve in occlu­
sion was better lhan observation alone, lhe 1-mg dose
had a better safety profile than the 4-mg dose.124f More
recently, inlravitrea! injection of ranibEmmab and dexa-
melhasone implants have been shown to be belter than
observation alone; however these studies have been short­
term studies lasting up lo 6 monlhs only. l-‘r '-| j '1
Surgical incision in the area of the sclera at the junc­
tion of the scleni and optic nerve dura has been sug­
gested as a means of relieving obstruction o f the cenlral
retina] vein. iJ Radial optic neurotomy by introducing the
microvitrectomy blade into lhe optic nerve and dchiscing
the lamina cribrosa and the compartment behind it does
nol have a strong rationale lo be effective, '['hose eyes thaL
fc. 7 7 Id itjpa Ih iс centra I reti nal ve in obslru с lio n
associated wilh opiic disc edema ("papitlophiehilts'7).
Л —E: O pt с nerve heat! swelling asstjcia Led with partial
obstruction of [he cenlral retinal атГег) and vein caused
acuta visual loss in the Left eve of this heal I by 31 -year-old
man. Kolo the vent l.-- dilation. с:pl i ■I : - iivl prr papillary
relinal hemorrhages, and ischemi< w hilen ol the relina
centrally iA . Angiography Tovealed early rc>tiплI artery fill­
ing al 21 seconds (Йг arrow), and nc venous perfusion al 35
seconds (С). Lchography of the optic nerve and orbit was
negative. Two weeks Eater there w ere more peripapillary
hemorrhages and some vifroous hem orrhage but Less relinal
ischemia ID). One* year later Ihere was mild opiic atrophy
it.. Hrs visual acuily was 2Q/70. The righL eye was погтаГ.
F-J: This m ildly hypertensive 40-year-old man presented
with vision change in his riyht eye to 20/25. Feripap i 11ary
hemorrhages, totlon-w<Kjl s&o1srF dilated and tortuous veins
were seen in the rj^ht eye IF). The left eye was normal; note
an absent o piic disc cup lG). Extensive workup done else­
where, including coagulation pmfile, collagen vascular,
carotid workup and magnetic resonance imaging ol bis head
revealed no other abnormal ity. The retinal findings reserved
over -E monlhs [llj approx iт а icily ti weeks alter the onset in
his right eye he noled a change in Jniн lull eye. His vision was
still 2W20 but he had peripapillary nerve fiber whitening and
hemorrhages, dilated and tortuous relinal veins and hemor­
rhages in all four quad rants il-h.. The relinal findings resolved
over the following 3 months and his final visual acuity was
20/15— in each eye. The left optic disc had mild residual
pallor (Jl.
К: Combined cenlral relinal vein obstruction and branch
relinal artery oEjsLruclion associated w ilh л swollen optic
disc in an otherwise healthy 31-year-old wom an whose
visual acuity was 2 0 /2 0 bilaterally. The LefL eye was nor­
mal. Angiography revealed evidence cfT central retinal vein
and tiranch arlory obstruction and staining pf lh e ri^ht optic
disc. Echography of lhe opLic nerves and orbit was nor­
mal. Her pasl medical history was positive only for the use
of birth control pills. Two years laLer her visual acuily was
unchanged. The fundi w ere unremarkable except (or seg­
mental optic alrophy in lhe rig)il eye.
L: Acule loss ol vision caused by lar^e prL>macular hem a­
toma that was associated with swollen opiic disc and cen ­
tral retinal vein o Ejs I ruction i-п a 4 1-year-old man. There were
scattered superficial and deep retinal hem onhages as well
as extension o f blood into the vitreous near the optic disc.
Anjjiogjaphy sEiowed evid en ce of increased relinaE circula­
tion time and probable location ol a large hematoma in Lhe
subhyaloid space.
have improved following ihis procedure have done so by
lhe development o f collateral vessels between lhe retinal
venous and choroidal 'venous circulation. 'Ifiere is experi­
mental and clinical evidence that production o f relinocho­
roid aL anastomosis, using photocoagulalion distal lo the
site of branch venous thrombosis, may be efficacious in
relieving outflow obstruction {Figure 6.S3J. El6J-: J

B R A N C H R ET IN A L V E IN
O B S T R U C T IO N
ilranch relinal vein obstrucLion typically occurs al an arte­
riovenous crossing in middle-aged or older paiit’iils.. who
in aboLil 75 % of cases have systemic hvperlension (E'igures
6.7Д and 6 Ц 7 9 i Ss-i an T h e
o f lhe obstruction is thrombosis occurring at the site
where the artery and 4rein share л common wall. 1172 The
obstruction involves the supero temporal vessels more
frequently, probably because of lhe greater frequency of
arteriovenous crossings superiorly.'■ 2M-' ■ Ш М * 7* At
the obstrudion site lhe relinal artery crosses anterior lo
the vein in 53-У99a of cases. Patients typically seek treat­
ment for visual loss secondary to a localised, often fan­
shaped area of hemorrhage and exudation, lhal extends
from lhe site of the obstruction to all or a portion o f lhe
superior or inferior half o f the macula [Hgures &.7ЙЛ and
6.79H and Kj. 'Jhe sile of the Obstruction al an arteriove­
nous crossing usually can be delected near lhe apex of the
Lesion. IE may, however, be obscured by intraretinal exu­
date or hemorrhage. Collateral vascular channels may or
may not bridge the site o f the obstruclion or be evident
along lhe horizontal raphe, in Severe cases blood and exu­
dates may dissect beneath the retina in the macular area.
]he presence of cotton-wool patches arid loss of transpar­
ency of lhe retina indicate a greaLer reduction o f blood
flow in the area o f lhe obstruction. The degree o f central
visual, loss is variable and initially depends primarily on
the degree o f ischemia arid on the amount of blood and
exudate in the cenlral macular region, in some cases exu­
dative detachment o f the macula is the cause of visual loss
[E'igure 6,7 9 D ) J1 1 1 The relinal hemorrhages
gradually clear over a period o f many weeks. Varyi tig
degrees of capiilary dilation, secondary capillary retinal
telangiectasis, capillary loss, chronic retinal edema, and
retinal atrophy remain as permanent residua of the venous
obstruclion (figures 6.7Й and 6.791). In approximately
50% o f patienis, the macular edema improves and visual
acuity returns to 20/40 or better within 6 months (E'igure
6.7Й13}. En other patients the edema may continue clear­
ing over the subsequent 6-12 months. Dilated collateral
channels bridging the site of the obstrudion and develop­
ing along the horizontal raphe and papillomacular bundle
region become more apparent as the blood and exudate
resolve (figure 6.7&L>). Figm entary changes in the mac­
ula secondary to sub retinal blood, development of large
irregular cystic spaces in the macula [E'igure G.7SG), and
Lbinning and macular distortion caused by an epi retinal
membrane o f the macula are late changes seen in palienls
whose cenlral vision fails to improve beyond the 20/40­
20/50 range. 3n some cases lhe secondary retinal capillary
6 .7 8 EJra n с h re lin a l v e in о bs Iru c t j o r .
A—F: Intrarelinal hemorrhage secondary to branch vein
oEjstruclion in lhe macula о1 л patient whose visual acuity
was 2 0 /2 0 0 (A). liLood obscured № t site of lhe obhlTuction
at the arlerLovenous crossing. Anj^io^aphiy showed evidence
ot a dilator I c a p ilW y bed in lh-е paramacular rwjion and
permeabiliLy alterations denpik1 lhe presence of blood Lhal
c .,u s e
obscured mosl df 1h-cj details 01 I he underlying retinal ve*-
nels '!t? and C). Twenty-1 w o monlhs later I Ere blood hud
resolved rD). Visual acuity was JIU/3Q. In Lhe area of previ­
ous hemorrhage Lhene Were HheaLhod vessels anti dilated
relinal captflaries. Collateral vesSela w ere evident at lhe site
ot Lhe previous block ( i t row, D )r as well ак nlonf^ Гhe; hori­
zontal raphe and nanalty lam jws, £). Angiography revealed
evidence of secondary capillary Lelangieclasis and minimal
evidence ol" leLinal oot'ma in the par.n'uvoolar «ген ■b and L i.
G - l: Cystoid macular edema (C M EI caused by secondary
Lelangieclasis follow ing obstruction of tw o branch venules
La nows, C;- in a ft.5-yea r-okl man with a fr-monlh history of
blurred vision. Visual acuily was 2(.V50. NoLe lhe C M E in
an otherwise normal-appearing lundus (G.i. Earlv angiogra­
phy revealed delay in filling of the inferior m acular arteries
and venules 'H i. There waii dilalion of the capillary hud in
Lhe region ol 1he venular obstruction larrows, IJ. O n e hour
afler dye injection lhe an^io^ram showed lhe lypical paLtern
ot C M E.
J-L: Thin 4ft-year-old man W ho i years previously had 1ran-
Kienl loss of cenLral vision in Lhe lefL eve because of acute
Ejranch retinal vein occlusion developed sudden loss ol
centraE vision in Lhte same eye w hile dij^in^ in the garden.
This was caused by a fovfial hemorrhage :arrow, I occur­
ring in lhe area or" secOodartt capillary 1e3an^iL>cMsis, w hich
was evident an^Lo^raphicaLly (K and Lj. The Eremorrhaye
cleared over a period of several months and hrs visuaE acuity
iu!urned Lo 20/2 0 .
Itj-I, frum t j . i s v 1 -, S. 19Ы 1. Л п и т к и п M e d i c ,il AhbLniniLicjn. A l l и^пГь
rLscirwtl.J
telangiectasis is associated wilh a pattern o f circinate reti­
nopathy [E:igure 6.Й0С and h). Ln palients wilh hyperl ip-
idem ias the amount о/ yellowish intra- and subrelinal
exudation may be extreme.'■■h! In a few cases there п\яу
be extensive focal aneurysmal and diffuse dilation o f the
retinal arteries, veins, and capillary bed.1'0: 13a3^ l2&’ Such
cases may sijnulate closely congenital relinal telangiectasis
(figure 6.43 and 6.44).IJiU- bolitary anerial macroan­
eurysms, which are also common in hypertensive patients,
may occasionally accompany branch vein occlusion either
remote from or within the region of venous obstruc­
tion [E-'igure 6.2LJ]j. Multiple branch vein occlusions т л у
occur in one or both eyes. Occasionally the occlusion L7i;iy
involve two adjacent venules in die macular area (E-'igure
6.7&). Visual field studies in patients reveal arcuate scoto­
mas o f variable density depending upon the severity of the
venous obstruction and secondary retinal ischemia. ' J
 fluorescein angiography during the acute hemorrhagic
phase of (her disease may show nothing more lhan a large
nonfluorescent area Where Ihe blood obscures both the
relinal and choroidal circulation [t'iguie 6.7BA-C). late
photographs are important in detecting evidence of intra-
relina] extra vasal Lon of dye, which may ел lend beyond the
area of hemorrhage. A focal area of dye leakage may occur
either al or jusl proximal lo lhe site of the arteriovenous
crossing [i'igure 6.7S). 11 occasionally occurs at a focal area
o f Venous wall decompensation before the development
o f the venous obstruction. Angjography may demonstrate
either complete or incomplete venous obstruction al the
arteriovenous crossing and usually shows minimal inter­
ference wilh arterial flow."'''1 Collateral channels bridging
the site of the arLeriovenous crossing and draining into
adjacent quadrants usually become evident angiographi-
cally as the relinal hemorrhages begin Lo clear (I'igure
й.7ЙЬ. and Fj. Ihese collaleral channels typically do not
show evidence of dye Leakage during the early stages o f
venous obstruction. After resolution of Lhe hemorrhages
and restoration o f relatively normal intracapillary pres­
sure. angiography often demonstrates residual damage to
Lhe structure and permeability o f the retinal vascular bed
(E'igure F| J I, and I. 6.79 if and I). Ouring the early
stages after branch venous occlusion, lluorescein angi­
ography demonstrates increased relinal circulation lime,
evidence o f capillary leakage, and perivenous staining in
the obstructed /one. W ithin a matter of weeks or several
months after partial clearing o f the subrelinal blood- angi­
ography in patients wilh relatively mild venous obstruc­
tion typically shows varying degrees o f mild capillary
telangiectasis, dilation o f the collateral venous channels,
and staining o f the retina, including Lhe typical pattern of
C M E In some patients with persistent sub no ranaI visual
acuity, Lrt patients with more severe acute venous
obstruction and retinal ischemia, large areas o f capillary
6.7'J Branch retina] vein obstruction (BRVQ).
A -С: ThLs Э-З-уеаr-old Othefiwise heallhv Wqman was Seen
because □[' blurred vision in the right eye associated w ilh
small ruling I ftjferntjfthages in Lhe interior half o1 Lhe macuia
and a fa ta l area af whitenjnj; (А) а I ап inferoLempofal reLi-
naf arLery and vein t russing siLo where angiography revealed
a local area o f staining iarrnw, Й). The foveal ca-piliaries
showed leakage wrth dye accum ulation in a cystoid paLtern
ft!:. A ll syslemic investiyalicms were normal and she was
normotensive. The venous endothelial damage at the site of
an arteriovenous crossing may Ehj responsible far the KKVO .
D: Serous delatlrm enl of Lhe macula (arrows, caused by
&KVO.
E —Iг Thin 5 4-y ear-old hvptfrlensive wom an presented w ill:
sudden superior field change rn her ri^hL eye from a local­
ised H R V O and a vision of 20/40. W 'ilhin a w eek her
vition dropped '.o 20'200 w hen Ihe cysloid macular edema
iCML.i increased in size -!H). ^he rfec&jved an inlravilreal
injection or 4 т ^ Triesence, which promplly resolved Lhe
L.VlL I <Li|i and vision reLurned to 2tV30. №y Э months she
developed a small tW L It-I and i arrow I in spite of lim it'd
nonperfusion requiring scalleF laser Lo the affected quadranL.
) and K: This frO-yea г-old asymptomatic wom an w ilh a
foveal-sparing Hupefioj liK V O (Jl progressed v.'ilh increase
in hemorrhages, venous lofluosily, and development of С М Ё
over 2 monlhs (It). Note lh e со I laterals on Ihe o plic disc.
nonperfusion, which in some cases may include the mac­
ula, are evident angiographically and may lie accompa­
nied by retinal and/or optic disc neovascularization. Initial
reports described a poor visual prognosis in those palients
with persistent macular edema with angiographic evi­
dence of segmental nonperfusion of the peri foveolar capil­
lary netw o rkljrLI 1270 Mnkelstein, however, found Lhat the
prognosis for spontaneous visual acuity improvement was
better in those patients with angiographic evidence o f jux-
lafovea] capillary nonperfusion.1"^
 lhe deVtlopigeoi of retinal and op Lie disc new vessels Ь.(Ш Venous collateral varicosities causing late-onsel
Ё& one o f lhe major complications of branch vein obslruc- visual loss after branch retinal vein obstruction,
Lion.]271D' lja9,]MQ New vessels are most likely to occur in A Find E: Sudden Ioss ot cjtinlr.nl vision caused by bleed­
patients who Initially have multiple cotton-wool patches, ing from parafoveotar venous collateral variousilies in the
diffuse Ischemic whitening, and extensive hemorrhages left eye of <l 32-ytiar-old black patient with severe pupping
In the retina, and who Eater show multiple zones of reti­ ot 1h t!- optic disc and noirnaJ intraocular pressures* Tbcie
naE capillary nonperfusion. lhe new Vessels often occur was angiographic evid en ce o f occult superior hemirelinal
at the junction between lhe perfused and nonperfu&ed vein obstruction. hi is visual acu ily was 2£h'20, r if^hc eye, and
20/25r left eye. Note the central nodule o f altered intrarelinal
retina. Occasionallу,- however, they may develop remote
and subrelinal blood and I h r:- m ulliple patches of subrLlir>aI
from the zone o f relina affected by the venous obstruction blood (arrows, AI beneath the dilated venous collaterals seen
(Figure 6.801Ч and I ) . 114'1 i?etinal and optic disc neovascu­ best in the Sngldfjrarti <BJ.
larization Is less likely to develop in eyes after posterior C -E: Ciirtinate pattern of macular exudation caused by leak­
vitreous detach ment.1 n ' J' r ' lie Li nal neovascularization ing collateral venous channels (arrows, D) in a patient w h o
probably develops in fewer than 2 5 % o f pal Lents with bad evidence ot a previous infefolempoTaI branch relinal
branch vein obstruction- and probably 5 0 % or fewer o f tejn occlusion, NoLe ibe lale filling ot the aneurysm involv­
ing the b c l r a m l vessel it:.
Lbese ever develop a vitreous hemorrhage.l25fi Sheathing o f
F —I: Two years before ll>ese fjhoto^rap-hs I his patient devel­
the retinal arteries and veins In an area of venous occlu­
oped a superolemporal vein olrelrudion in lhe Eeft eye.
sion may occur in some cases.11и Other complications o f O ne year later his visual acu ilv w as 20/20. Vet 1 year laler
branch vein occlusion affecting the macula include dis­ it declined to 20/200. \ o te the circ.inate maculopalhy sur­
tortion secondary to epiretinal membranes, JamelEar and rounding aneurysmal dilation ot a venous collateral (arrow,
full-thlckness macular holes, traction relinal holes and temporal lo lhe l e f t mac. Lil a and lhe delay in perfusion and
detachment,|J" 1-1256 hemorrhagic delachmenl of the inler- incornplcHe filling of lhe aneurysm iarrow, £]l. Argon laser
photocoagulation (arrow, H) resulted in disappearance of
ttaE limiting membrane o f the r e t i n a , and rhegmalo-
the aneurysm and circinale exudale (Il. Ttiere wav minimal
gcnous retinal detachm ent/^''11^-12^ 1^ - ^ '^ Disorders
improvement in visual acuity because of subfovea I fibrosis.
occasionally associated with branch retinal vein occlusion Arrow 11) indicates site c*f aneurysm.
include optic disc d m s e n , sarcoidosis*1 ■ tomplasmo- I and K: Prominent venous collateral vessels simulaling
sis., serpiginous choroiditis, idiopathic multifocal retinitis a congenilal arltiriovenous malformation in a hyperten­
and neuroretinitis, acute intermittenl porphyria,: 1hyper- sive patient following a supurotemporal branch n ilinal vein
Eipidemia and hypercholesterolemia,1' 11 and beta-throm- occlusion.
boglobulln and platelet factor 4 abnormalitiesL,J33
Varicosities and decompensation o f venous collaterals^ Pholocoagulatlon treatment for the edemalous and neo-
usually along the horizontal raphe, may be a delayed cause vascular complications o f branch relinal vein occlusion has
o f loss of visual acuity many months or years after reso­ been investigated by numerous authors.1^ 1J l:i-1J ] 307-t3]S
lution of branch retinal vein occlusion (figure 6.H0).1' " 1 A randomised controlled clinical irial has demonstrated
]hl& complication typically occurs in patients wilh a large ill at a scatter pattern o f argon laser applied lo the area of
/one o f capillary nonperfusion in the area of previous vein capillary leakage within the macular area and outside the
occlusion and is associated with die development of л ring ¥AA was o f value in preserving central vision in patients
o f yellow exudate surrounding the foveal side of the leak­ persisted rjiarnlar edema and visual acuity of 20/40 or
ing collateral vessels (Figure 6.80). On occasion, acute worse (figure fc.70A-l-').L- ':'A Because of the relatively low
bleed ing from the collateral vessels into Lhe sub retinal frequency of development of neovascularization, periph­
space may cause visual loss [I'igure 6.ЗОЛ and B). eral sea tier photocoagulation was recom mended as a means
I [istopathologlc examination o f eyes with branch reti­ of reducing lhe risk o f vitreous hemorrhage only In those
nal vein occlusion has demonstrated a fresh or canalized '■
■
■Im: du:n MisLra-ed neoYiisai l,ni::.:.M- т. iiia v m:
thrombus al the site of obstruction and varying degrees o f evidence that pholocoagulalion during the acute stage of
sclerosis o f the wall o f lhe corresponding retinal artery al branch vein occlusion is of value. Jjs e r treatment is of bene­
the sile o f the obstruction. ! ]QJ Inner Ischemic retinal fit for patients frith delayed loss of vision caused by decom­
atrophy, relina] neovascularization, 1I1MA, and СМ Ё and pensation o f venous collateral vessels [ligure &.&£)).
degeneration are found in the area o f the venous occlusion. lixperimen tally recombinant tissue plasminogen acti­
Many of the ophthalmoscopic and angio­ vator is effective in lyslng laser-induced branch retinal
graphic changes seen in humans with branch venous occlusions In rabbits.ljL£ Surgical separation of
retina! vein obstruction have been reproduced experimen- lhe retinal vein and artery where they cross is technically
j.fowevtTi chrunlc CM E and possible jnd has been tried in animals and humans with
retinitis proliferans, which are o f visual significance in branch retinal vein obstruction, but its value in improving
humans, have not been reproduced. venous perfusion is uncertain."-l'
 Widespread retinal hemorrhages that may simulate
those caused by central rettn^l vein occlusion may occur
because of decreased blood flow lo the eye (carotid
artery obstruction1 ]R;; venous stasis retinopathy); marked
reduction in intraocular pressure (ocular decompression
retinopathy after filtering procedures)n i'’; capillary per­
meability abnormalities caused by a n e iq la , leukemia, and
seplic retinopathy; reduction of blood (low associated
with hyperviscosity (macroglobulinemiaj; and LransienL
rise in central relinal vein pressure associated with com­
pression injuries o f the chest and by mechanisms lhal are
nol well understood in patients with subarachnoid hem­
orrhage syndrome) and cocaine inhalation (see
Chapter У).
More recently, treatment o f macular edema second­
ary to branch retinal vein occlusion has involved lhe use
o f intravitreal triamcinolone acelonide, anti-VrbGf: agents
such as ranibizumab and bevacizumab, and long-acting
dejcamelha&one implants.’ '■‘u" 1i25 lhe belief lhal these
agents decrease vascular permeability is the underlying
hvpothesis of the treatment, lhe response is variable in
patients; in many the edema recurs once the treatment is
discontinued unless the eye develops adequate collater­
als: this is the only certain mechanism for resolution of
edema. It is reasonable to consider any of these treat men Is
till one can either demonstrate development o f good col­
lateral vessels, or not, in which case no treatment is likely
to improve vision and edema.
t .S E Laser tre a t m e i t lo r reti г aE ve in o b s tru c tio n .
A -F: Sm;dl branch retinal vein obstruction ели hi ex и da live?
m aculopathy i A - U j . The visual acuity was 2(VdO. hive ye art;
following ar^on laser photocoa^uliition ;El, I Imre was m ini­
mal exudalinn (F) and visual acuily was 20/20.
G and H : This palienl developed nplic disc and Totrnal neo­
vascularization (aftrJWS, Cl and a Trmcular келг following an
inierotemporal branch vein occlusion. Angiography showed
marked lost of Lhe retinal capillary bed in the area of relinal
vascular sheathing inferior In [he macula. A scalier pattern
ol argon la-Mjr trealmcnl was applied lo lhe area of capillary
nonpenfusion. Twelve months later the disc and retinal nen-
vasculari nation had nesalyed IH .
3—L: Laser reLinochoroidal anaslomobis in the trealmenl
□f central relinal w in occlusion in this patient, who енре-
lienced pfojjressive decrease in vision (I), Several months
following Intense 0. 1-second. 50-|im laser appjicalions
Lo create a netinochoroidal venous anastomosis inferiody
tarrow, 11, lhe relinal hemorrhages had cleared. The laminar
flow pattern in lhe an^io^rams in Mica Its retrograde ilow pf
venous blood toward the anastomotic sitelarrow s, К and L).
11—I_Irrjiii M cAlliskT i n i С йлЙ лЫ с.1 i I № 5, AiraTft.jn Mt'cl.L.il
Амгл .,|Иип ЛИ мц!'1ь jl-^l t v it : ■

Hemi retina I Vein Occlusion

Retinal vein occlusion may invoke half o f the fundus and
may be caused by obstruction o f one of the dual, trunks of
the central retinal vein (I'igure 6.7У ] and Kj, an anomaly
Lhal occurs in approximately 20% of individuals.1 1iJ"
The; obstruction probably occurs at the level o f the lam­
ina crib rasa and palhogeuetically is more closely related
to occlusion o f the central ralher than the branch retinal
veins.
RETINAL VASCULAR CHANCES
CAUSED BY HEMATOLOGIC
DISORDERS
Changes in the composition of the cellular and extrace E]u-
Ear components o f blood may alter its viscosity, flow char­
acteristics, coagulability and transport system for Oxygen,
carbon dioxide, and olher metabolites, which in turn may
cause alterations in the retinal blood vessel caliber, length,
color, nind permeability Some of these blood alterations
have been discussed previously, such as sickle-cell disease,
thrombocytopenia, disseminated inlravascular coagulopa­
thy, and complement-activated leukocytic aggregation.
Alterations associated with leukemlas are presented In
Clhapler 13.
Retinopathy Associated with Anemia
i\ilients wilh moderately severe or severe anemia may
exhibit fundoscopic changes, including flame-shaped,
white-centered, and subinlernal limiting membrane hem­
orrhages; coLlon-wool spots: retina! venous dilation and
tortuosity; retinal exudation; pallor o f the fundus with
increased choroidal markings; and optic disc sweEling
[Enures 6.Д2А, fi, FP ]. and K, 6.S3 A-E and 6,84 B-F), in
some cases intraretinal hemorrhage may be associated
with proliferative relinal rascular changes that may simu­
late a retinal vascular hematoma (I'igure 6.82Г and G } ■'
Retinopathy is more likely lo be present in cases o f
rapid development of anemia and in older palients with
anemia.1 : Unless one of the hemorrhages involves
the central macular area, the palient usually has no visual
symptoms. In som.e cases o f severe blood loss, retina! and
optic nerve ischemia may be associated with profound
visuaE loss.i:m -tm
A small subset o f patienls with anemia may present as
idiopathic intracranial hypertension with bilateral papill­
edema, peripapillary hemorrhages, retinal coLton-ivool
spots, and prerelinal hemorrhages.1',ilr" 1 ,1 Cerebrospinal
fluid pressures are normal and so Is the KdRl; these
palients may have severe iron-deficiency anemia. As soon
as the anemia is trealed, their signs and symptoms o f pap­
illedema, relinal hemorrhages, and cotton-woo! spols
resolve. Anemia should be considered in Lhose patienls
6.8^ A n e m ic с h ori ore lin o pa thy.
A - D : This 1?-yoa r-oid wom an noLed а scoLoma in lho lefl
eye w hile in lhe hospital for IxeaWrttfit □( severe anem ia ,ind
idiopathfe thromEjocylopenic purpura. Her h emogl ob in was
2.9g/dt and humalocril was 3 % . Note the superficial relinal
hemorrhages in bath eyes-, the prominent chorojdal vascular
markings, lhe Eighit color pf lhe fundus, and Lhe relinal ves­
sel fcrtutisity iA and LS.I., all □( which disappeared after blood
transfusion and spleneclom y IС and P :.
E-l: This .J-ycar-old c h ild w i lh K lip fje l- T r e n a u n a y - W e b e r
s y n d ro m e d e v e lo p e d s e v e re Eiemolytic a n e m ia , th ro m b o ­
c y to p e n ia , h e p a to e p le rto m e g a ly , h yp e rte n sio n . a n d c h r o n ic
re n al 1л i I Lrrc.1. H er hervioyiloEnn w a s 5,1 g/dl a n d h e r hematei-
cril w a s ] 5 % . 5up eronasa3ly in the right ^ye (E an d Pi, and ir>
lhe? left m a c u la r area s h e h a d Iw o fo cal a re a s ot" inLrareli-
n a l h e m o rrh a g e , re lin a l Lh icken in g . a n d m ild lv d ila te d c a p il­
laries s u n o u n d e d Ety y e llo w is h u x u d a lio n The a p p e a r a n c e of
the fundi w n s s im ila r to that illu strated in p Eio to yrap h s m a d e
at ag e 2 0 m o n lh s [E—C ) . 5 h e a p p e a re d lo h a v e g o o d v is u a l
a c u ilv in lhe right eye, w h o s e m a c u la w a s u n a ffe c le d b y Lhe
re lin a l v a s c u la r ch a n g e s. W h e n se e n al age 20 m o n th s the
fu n d u s c h a n g e s w erL" in le rp rc lu d as re tin al v a s c u la r m a l­
fo rm a tio n s .1 Т Е » a u th o r b e lie v e s lEial Ihe re lin a l c h a n g e s
w e re m o re lik e ly a c q u ire d as a c o m p lic a t io n of an em ra,
LhromE>ocyLopenin, a n d H yp erten sio n . Nole lh e telang iectasis:
ot" lh e le y an d fo o l ( H a n d lj.
J-L: This 2ti-year-o3d Lalir* man w ilh anem ia ■hemogl oh i r*
6.3g/10Dmlj rtilaled Lo treatment for acquired immunodefi­
ciency syndrome HAIDS) developed bilateral blurred vision
causrcl hy sub internal limiling memtirane hemorrhages in
lhe m acula bilaterally. NoLe Ihe widespread white-centered
superficial retinal hemorrhages I and jt). Three monlhs later,
afler correction of his anemia, lhe hemorrhages w ere gone
bill Ere had developed cytomegalovirus relinopalhy in lhe
inferior macula area of the left eye (L\
11, frurn Brtjd ft .il.1
w h o d o n o t fit the usual p ro file o f id io p a lh ic in tra cra ­
n ial h y p e rte n s io n o f excess w eig h t a n d w h o are o th e rw is e
negative fo r o th e r causes o f isolated, p a p ille d e m a . A n e m ia
associated w ilh k id n e y disease an d d ia b e tic n e p h ro p a th y
m ay aggravate lh e retin opathy, lh e re !alive h yp o x ia causes
m u llip le- o rg an tissue in ju jy . T h e re h ave been cases o f anc-
m ic re tin o p a th y w ith m icro a n e u ry s m s an d d o t- b lo l h e m ­
orrhages, all o f w h ic h reversed as so o n as the a n e m ia w as
co rrected .M ',,J T h ere have been reports o f b ran ch retin al
artery o c c lu s io n In pa Lie nts w ith iro n - d e ficien cy an em ia.
 Anemic retinopathy is often characterized by W o t
hemorrhages that look like ли ink dot made up o f mul­
tiple tilde dumps of red blood cells [ligure
Ё5 believed that lhe low oaygen-carrying capacity causes
damage lo the endothelium and the blood cells seep out
Lbrough Lhe damaged endothelium and hence lhe hem­
orrhages are more like an ink blol rather Lhan nerve fiber
Layer or more dense. Along wilh the blot hemorrhages, lhe
wins are dilated due to auloregulalion and as a compensa­
tory mechanism to decrease lhe flow through the retina lo
extract as much oxygen as possible by the relinal cells.
The cause o f anemia, as well as accompanying hemato­
logic abnormalities such as thrombocytopenia, leukemia,
and macroglobulinemia.. may be more important lhan the
Level o f hemoglobin in lhe production of retinal hemor­
rhages. 1 33J' 1 ' t U i I hrombocytopeni a. thro mhas-
thenia, and other platelet abnormalities in lbe absence
o f anemia may be the underlying cause of relinal hemor­
rhages' ' ’*■1' 1" and retinal edema ( figure 6.£j4tl-] ].
6.БЗ Anemic retinopathy.
A—D : This 45-year-old wom an w as post unknown donor
Е1]. IL р в п р К й в ! stem cull transplant lor acute m yeloid leLiltemiiii
w ho hiid developed erafI- versus 4 lM l disease i C v H D 'l Her
v if-ion wan 20/40 in- uaoh eye. iihe had bolh nerve? fiber and
deep ink blot-type feLlnaJ h ^ r o lt b a ^ I'arrow.i.. some w ilh
w h i t e c e n le T S (arrow ), secondary to anem ia le ia ie d Eo her
blood dy*CM5i<L iA -D ). The retinal hemoirrhajjesi resolved
o n c e h e r n in y m ia im p r o v e d .
E: This 53-ytiEir-old patient had advanced glaucom a and had
undergone repeaL кета Iop Iasi ies in this eye. 5he was found lo
have several tar^eL-shaped Ia n o w i deep retinal hemorrhage's
typical o f anemia during her posloperaLive vis-iI. ih e had
anemia o f chronic disease w ilh a hem oglobin o f 8 .4 ^ 100ml
Lhal improved lo I 1 ^/IGOml with IreaLment.
Retinopathy Associated with
Hyperviscosity
lh e hyperviscosity syndrome consists of a bleeding dia­
thesis,. neurologic dysfu net ton.- and retinopathy that maj^
be associated with monoclonal gammopatbies such as
Waldenstrom's macroglobulinemia. [Clients who have
Waldenstrom's Enacroglobulinemia h a v e a high intra-
vascular concentration o f an abnormal monoclonal IgM
prole in that causes increased blood viscosity and intra-
vascular volume. I h is may produce the hyperviscosity
syndrome associated with fatigue: headaches; epistaxis;
visual impairment; sausagelike dilation of retinal 4t"ins;
increased venous tortuosity; dot, blot, and flame-shaped
retinal hemorrhages: retinal and optic disc edema; and
retinal detachment {figure 6.&4]-L.).: 1Uh En addition
to increased retinal circulation time, angiography may
demonstrate areas o f capillary nonperfusion and micro­
aneurysms. Serous deLachment of the retina in the macula
may occur in some patients with Waldenstrom’s macro­
globulinemia and other dysproteinemias (see Figure 3.60).
Plasmapheresis can 1 о Ш senun viscosity and reverse the
retinopathy.1 Ocular signs of serum hyperviscos­
ity may also occur in patients with multiple myeloma.,
polycythemia, or leukemia, and in patients with poly­
clonal gammopathies, most of whom haw rheumatoid
arthritis.1ч-1-' 1^ 0 Severe occlusive and p ro life ra te retinal
vascuiopatby may occasionally occur in association with
systemic light-cbain deposition, a plasma cell dyscrasia
associated wilh a monoclonal paraprotein spike that may
occur in the absence of the hyperviscosity syndrome.11111
(э.Й4 Retinopathy associated with anemia and
dysproteinemia,
Л -F: Subconjunctival hemurrhage (A.i and bilateral loss of
cenlral vision caused by m acular hemorrhages in a pnIiftihI
With aplastic anemia. Note lhe fine whiLe dots on the sur­
face of lhe !>loud narrows, li and Cl, w hich probably lies
jList beneath the internal Ii n^it injq т е т Ь м п е . Several small,
white-centered, superficial retinal hem onhajjes were presenI
I.D). Angiography IE and F> shewed гю evidence of vascular
permeabiliLy a hern) ions.
G - l: Retinal vascular leakage associated w ilh plalelet Abnor­
mality in both eves o f This asymptomalic 6-yoar-old biack
boy vuho had elevated Ejeta-lhnjmboglobulins.. К'рсгавдго-
^able pfhteletir Increased platelet factor IV. and m k rt icyl o-
nis. Visual acuity was 2G/20. The posterior iandi appeared
normal (Gl. There went! no Lulls in 1hci viLrutruh. Angiography
demonstrated marked roUna] venous and ca pi I Ian- O scu lar
pormeabillt) alter.i:ion> in bt'lh ovos И and I ■
. ! x'unMvo
medicas and hematologic ev a I иа Li ons w ere otherwise
ne^tive.
|-L: Ruling] hemcirrhayei and venous; engorgement in a
patient vviLh W aldenstriim s macruf’lobulinomia. Note the
I ink-на usa^e changes :arrow s. L and mol tied fluorescence
Within lhe dilaLed relinal veins.
К .' I, '. i:iurlL"y i.'l Ur. ^HLirrdL'rs L. h luf>|j.■
Hyperlipoproteinemia
Kive types o f hyperlipoproteinemia are described.1!53 Kach
has дп abnormality of one or more o f lhe plasma lipopro­
teins,. chylomicrons, beta-lipoproteins, or pre-beta-lipopro-
teins. tach may occur as a heritable disorder or secondary
Lo oilier diseases, particularly diabetes tnellitus. Lipemia
relinalis and lid xanthomas itray occur as complications of
types 4 and 5, bolh of which arc characterised by increased
very-low-density lipoproteins (pre-bela-lipoproleins)
and increased serum triglyceride levels [I'igure 6.S5A-C!.).
Cholesterol levels л re increased in type 5 and may be nor­
mal fa lype A. Lipemia relinalis is believed lo be direclly
correlated with lhe level of serum triglycerides.: '■*’ : ■*
It usually develops when serum triglyceride levels reach
2500 mg/d I. lhe retinal arteries ami veins develop an iden­
tical salmon-pink color that may progress Lo an ivory or
cream color when the triglyceride level exceeds 5000mg/
dl (]:igure 6.85A-C). Ordinarily ihis is unassocialed With
a visual deficit, and the fundus rapidly returns lo a normal
appearance as serum lipid levels return toward normal.
Jhese p^lienLs usually do not develop retinal hemorrhages,
collon-wool patches, or exudation. -155
W hen hyperlipidemia is associated with other diseases
afleeting capillary permeability, unusual amounts o f intra­
retinal hemorrhage and exlravascular intraretinal accumu­
lation o f lipid may occur. lji'c'-1yr'7 Some patients who have
excessive accumulation o f yellowish, lip id-rich exudate in
or beneath the relina associated with frequently encoun­
tered disorders, such as choroidal neovascularization,
diabetic retinopathy, and branch relinal vein occlusion,
may have an underlying hyperli pop role inemia (figure
6.-35t:-l.).liia Reduction of the amount o f circulating
bfood lipid may reduce the severity o f the exudation.8™
Hyperlipidemia in palients with proliferative retinopa­
thy may occasionally resull in lipid iransudation into lhe
b .f lj RelrnopaLhy associated with hyperlipidemia.
A—С : Lipem ia relinalis in a patient before (Af and aller
IB and C| developm ent of lipemia relinal in. Note the pallor
□I (he m ajor retinal vessels, w hich had a salmon-pink hue
IH Lind C).
D -F: Cherry-red spol mamEopathy and visual loss lo ГУ30
occurred bilaterally afler il weeks o f hyperalimentation in
this 23-year-old man with weight loss and fever caused by
Crohn's- disease (D). Angiography was normal tE>- The relinal
whitening disappeared and Erie acuity relurncxJ lo normal
within 2 weeks after discontinuing parenteral nulrilion iF-..
The relinal whitening was presumed lo l>e caused bv tem­
porary accum ulation ol" lipid bv Ihe ganglion pelb during
hyfH?*nlimentaLion.
G —I: This- palienl, w ho had diabetes, hypertension, Hind
hyperlipidemia, developed focal mounds of intraretinal hem­
orrhage and Tipid exudation 1GJ and angiographic: evidence
of dialled m icrovascuiar changes а1олщ lh e major vascular
arcades, in both eyeslH ?. Angiography demonsEraled minimal
evidence of diabetic and hypertensive relinopalhy oulside
the focal areas of exudalion and hemorrhage. The exudation
Mod hemorrhage processed 1o involve the centra] m acular
nren a f :b oth eyes w ilh in 9 muni h я -I'.
J-L: PnMraSsJwa loss of visuFil acuity occurred w ilhin t»
months in ihis ftJ-year-old wom an w ilh diabetes mellilLis,
hypertriglyceridemia, arLhrilis, gout, and an inierolemporal
branch relina vein obslrLKlion. Nole lhe increase in lhe hpid
eKLitLilion and Ihe jujdapupillary hemorrhages w hen her
visual acuiLy hnri dec lined Lo 20/400 ■Lj.
llJ - h Ггигп V jk ljt rt ,1! 1 J-L. CfiUrjfcy ol [Jr. K i n k J. (. u lk jll.n
vitreous, producing a picture simulating endophthalmi­
tis.- u 'I'here is some evidence that patienls with hyperlip­
idemia, particularly types 4 and !>, have an increased risk
of developing retinal venous obstruction.13SS
Parenteral hyperalimentation of lipid may occasionally
result in focal intraretinal extravasation o f lipid and blood
{ Figure 6.
References 42. G'&ieisa; E A talo H iaisan a m B n n if (he rptra: a ж-в cf ям r t f cole trcm bffi t; sn d
‘heal rg'. ^ Cphl'elioDi 19£l .5&937-S.
1. Effnj EM F M lire Tdiiasrcis ft'Me re 1ris^Tiiilalsr en mi Vа^йЕкИш Kir- r.'aiatsti fl3. Иг;ам!а t, <3"amjf W, M i hia K l. el a! Anomalous [га^Иг 'йжйь case repa1& d ibmsw
AugaihdW 1958^3253240. a! Lie recerl J^ar^a ita a u t Am Mithinol l9flG22i04-&.
2. m n a -. Salna1 Berrao ziir ^unfidren -Лjcfilas За deiien MedhaJBdSrtai. hefa-G, 3m i , -яН Л. si TheWitum-Masai аугягс-те. ortantaif ch asira aid
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3. Cag an1 6. Zur toanltfe bale cer laTtlaiei TcitLJim oer kjerei Пеншидейж 40. Hcimdi Т. Сйи JOW. С&с \L АЯегШиУе ''ikf ,^vilton r f t iei гa of a marJ^/. A n .
Oatta ma &g ca ’i9C3;15£:32?4 Op-it-ai'icl 197^:32:0st-9M.
■i. Cag anj: 0. 'A'eтег H Zun t ’asiklieitsbid Ja lami и ф Ta"!i>:ebla: da fen a Hedha.rainereri 43. U ii:a ^ Hender EF: M:F^l ТА. Ca Jial тешатойта г Те mad a. vjtdi h^i Hjpce ; dяа;е:
ritM aaM lJuig.W h MniijmAfcjentetfcl 1953:1 £3633-42. reral ■? a aae. j Oral 3jg tVeah Hctfj Deri Ser' W;22:2E2-9
5. Gc+le'g hff.PtrfachlRetal Facial retral aifcrida: tMtuosiy wtti 'eina hsTKmigs.Ajr j ^7. Magrijs H. Afe.rfEru als'Cfio-^m fr relict, 'itoiftm flidi Falicl A iiL' &7^£3:31146
CC*4tia ггэ" 972.73:1 S3-91 43. Наге1Я M. Sl: e ariim-iiie ce ^a:i si rici ea r ciucaar mada а1'атем:ша cim ce jela
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7. Кзг^л-.а1 M e ^ ii I Retral апепйаг Миж ty wlh там аг hervcn таде Ann [jpdlhalma № .M b -£ei,l 1:433-6
53. [Icnali H, Ciena .F, ^te1RFl. '^I'liai -si na Mei' acctaa'. ш л aled wn 'E nd ale t^oDuc
3. \Vdls OG. ^ ra 4E. P-oaesir/e i'icnlec rNnai iris car leduM^ ъ Ih ^ таг& 1 £refliii matnyiralcn.Ophliilic+Dg» Ж:133:24-Э|3
harcTrages. CphlruJnt+Dgy' ЭЕй:Э2:1 Cl 5-24. 01. T1ач;5 f.'D. Hsyti G. DeLlriin A" Gcftjenrjl i^ a ййчш; KrrmutaftDcs ай te
3. Fiaiisl IK. A itid £0. New тепа flakes CL^:g sclaiJ y&l eg r itetfM relnal ггегл ar ds^apfreT cl twe Npes у :мк ng "S1па: л’а'татеиг^ ms. An J 0 № a n:nl 1931:l 12:3'-3.
larUool^ArofcODiirairc' 995:11ЗДБ34. 52. M^bug MiKT fi А ш ^ я;аj] insinysri cf nid-tmr aid r«na \у^Игаил and meria
IQ Ceela -. Efcheda K. Ju g s M, et a Fairlcl тлna-alfiiil Vfljoahr aiscoala; mn МшаГг ^aogea 0ri>n 134Э:Ё&:* 63-2C2.
г пз1 к ] oap l arts. Ardi Oifiha o : 2006:124:1 4Э24. 53. Eilrcn _ 2з(ан;'П]Е,'53: ^ L.ris^ aJa' aausiisasa Jo p K flo n o FT jetyb in ^ sti
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12. Em >. <r, I. Vj RG A c a t cl oarciid aie ur/sm r-fan la! гала arts al m.tirty. Kc'tir J netOTS аме^ Гаге^нге d u o de la iais el Галет cite с nsade di кг^хи. Ё il -.'jem Sk
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a m № . OptiPHlmcJ 1991:10a^3S6-ft. a w e . A^. 0 (№ M 1W [l tefoi-5.
14 Maeati ТА. imenled reina! тегс4в. baadrq. А'й’ Cptrsircl 1957:1 C6.949-E2. 5S. detrexm !L Fannie L. Allta WC ei ii. 'Лаaba rcflnqHiff is i& ^ d a It: a « ije n Ю1
10 £lf.-.tfi W, ilia KA. Itt e-rec relt'al 'jenau aeaJng An1J Cfhlhilfltf 1Sfi£?" 06675-6' reliral гтгЯ'Шаа. A^: GpiTal'icl 2Ю0:118 -4G-7.
16 Ей 1al о 4G. Vinwigaj Д, K Jairii J ei Li. 'ilasalar 'etna abw illie s :mec iafe^ cl mod 57. Kr zumi H .;£ T. 'iisri 7 et a. ianai a le tlir i "o aars-r?in' aic occgsila relinal
ntnanotHl d[щ як га л су j Redat 3X0 ;13fl:760-6 таж^екое! СртГсЬтс Slto Laiers. 2CC0 -^Ii:5l 2—£■
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2CtS;' 9 33-24 148-51.
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19 & Ш 1 GC. Usjca'gil L.^gibL'ga .J. el a. : rcieifa adeiii; t-аж -sс relraI cneha &3. Muioz F. Fk>]( edi G. ^o'S; FJ. s al Солдат relra анеомпа£ с о ш тсяй т
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21 Fi&genlnei L Gc-deJ V, Зя&» Д, et a. FKlira Jitens t ® w:i js ci.Arn ^pfliama' du'i'ij paitile relra torren t.Irrrt3j O^Jttiarra V s ii ?3(К;4'.2Й27-3£.
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lie ifiisi nesenai cl 3i cptic ncne clicma Ju ii Nebrc'-OEfiitisma l £66 б 1-6
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reiira vehorclfim Opntfiakralaij !99' 93:59^-601
343. Fehsi Л Antel М. 1ктагс reiral апивЬогв in arcac amsL Ann Q(flttflhul 1979,11.
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№ S a Jf® M ^ o G b i 1933:Эе:2Ы-12.
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Pedotrics 1972:4£:24^9.
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f o r t Ш ЯБйЗНк
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р д ж те AnJOptTtfislnKl 1994' 17Э02-Г
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339. Fjtfams RC. ^ fttaneoiE accluasi ct lbs сача! nei na artery ard nan. Trans^r СптГйСй
£k ' 979:77.1 ai-^9.
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391. M iK d DiRiiDCP йкнейн! nfKaamattEfretralwin сим вол. & JCcbltdmct
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399. de Йтеоа 1 Jampa iA H e aye n acee eralec hisleiG cn. II LxaiBec а т; js 30(айчгет5
al ite rema r-pal enli.A^OpMiafTcl 1934:1 EE3-73.
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w S 3(ris.Ljcet190fi;1ft^M .
432. D^acitn a . flSlncpett^wHi cemi3nr\4iJla tocn ^Iham ii 1965 74:734-6
433. Gas; шМ.АЙипезсег a^xraduc al macjar tfpfuncticii aectfldar- la rninal ^ialar
disease. II. -^eleis№ retmcpaffiv. Af?- upntancl 1953:Ёь:Е69-Щ.
№. &idMai(i Mi. ^Etnal dscfesscfl ii-r ndcalrg a recnai rtarul i\ir J ppClhaJma
1973.86:45-S£-
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4M. Непйпj P [toiler; 6T. PstDfflws^cDV al the retnal казаы bed latirtit aajte етвеапэг.
te C fh |-d T H l1 £ E 6 6 ffl£ -7 . '
437. НсСзе JV, -йа1ел' C7 Fleinel sar eaiHes, a ciacal sbf^ tw cd sj a d Нлгеасегсе
t m m . 5 J Med ■56433:11 M l
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Алл Ffsr-Dc 19Ё2:4' 473-6
439. PfetlEfbadi DC, ^cia-fn'srRV,- M iiem Rps^of the 'ennai als'clea Я . к
1973 225:4аС-3
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1962 89:1132-45
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156239:11^7-31
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iriben. J Felatr Opiralricl STsbiiirus' 99229:297-9
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199320324-6
414. Ganer^Astilaih. 'tHlh R FailmeTeas cl 1Г|р?1елйке slnapallrr: ar enpefrena stua^
415. Kafnaav.a F. Hcrca A Seniem ml na use J s leva's In Ix ts Егчвнлаош. ton
OpTtaml 1981:1112934
AM. Ncdnski I tier. amixV, ria call M. el a. Ocuar i^atemenl г 143Ш erymeiralcejs a :n.fidjl
Ipannicu il a.- Oaita inlc^ 1962 89.114Ё-&4
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1932:54.666-9.
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424. AiaxraiGK Bofcbero MF JarpoEL.eta. № ti^ maawnfurysms. An?t Optiruimot
1S77fl6:62M.
426. A/ns l_F: Kr.nms'Hcfer TiL ‘^sata n aiutpDinr,' i e to a relral arena тюатеш уат. Arn
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426. Gass 1Ш OSais n the aealmet cl iraculsr OseaK. Tran: ОатТятс! See Ud
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424 Gass iH t i-teiHroaa alls rf irrculsr tiie a s : dacr osii arc treatment, 2nd ed. Si. L&je
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1973;Ё2:Ы&-57.
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432 Hudcn:t; J rlave i FhsncoDagJal on Гваигеп: cf ad a y aneiyan near tje писай k-tea
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436. PiJ^sl ns AG. Fuaeraor: DM. Ga ester EC. Наяшеитате cf the -st ra ateaa An' J
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440. 'ilan i Da-tKrai AF. Arca- laset lieii ien! -j ramal mama-&j ^ ts. In! ililhiJnid
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lis№y. flr J МтВДш* 1990:74:595-600.
447. PiraliiA.^MdKii&.TliEiocEiiaaiFG.ela l.iacraa eir/ime arens reliia'pubale:
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Ajn JGfhnalmd l5'4;77.4i>-.
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472 Jcrtan A_ E fiw n l Cadscn M. Pamacena? d aa^ahc n aais ecema Am. OmTarid
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473 'iasartlat) R6. Ш ш SC. Palsc ne AG. МзсJa r thc-jen rg ire hisuil acu t^1raasiiEment
n piieira v»t wila с macu ar edara. GfmriiJn>]*oc-s' 1937:34:1' 34-9.
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GcftlhslmJ 1563^7:321-36.
6 4 3iesnickGH Da^M l, W^s FL sial.C; -срапс+здс Krreiaicns i' cctsdiran'Dpallrn
I. Gin td irjG hslctoct: арка’апсез у гл гй apibr,' u s janfl.rfsn;a.Ajch 5pi;lli3mii
1377:56'213-20. '
6^3 Ere-HickGH H aj :B.cc'^nicaG Rehnjlwrknc anji-j?.taf neie'a^iiin aailic
■slnsHlIu ftich 1970 97:13SC-3.
6*6. Goiin D1 Ki/.^ilMra" Cici liTn stiuifis r tfe nlhxens s d ciahsi^ гя 1щ й 1гц basles
19E2.'2.293-2110.
6^7 Gopin D i "auasaM 0. Kir,-.lcra T. Relnsl ■ й &л.Ь г pallsrns V Daaeuc rrttropahy. A'X
^Itiam^1£6lfi6:33£-78L
6^3 de Vesi&iia G. Cafis M, Engerman R Ohcqpatt»opt csnebtys mdsfcedc lelincKitj1.t
-istaffljfii'a llLcreEffiinaigicfl,aa^cfn:i'™neurjBms.A,d-.OpntalncJ 197^:^ "!b6-72.
6 ^ ^]fns- EW; Daltov CT. F сjsscer ам йазйг ol 1П6lunJii л dabetra гй и ват. Er Med
Eut 1970:26:190-70.
6 jj ^]fne- F4. Codaff CI. Falssan J* ' ei a. Arlffel '.ts 'K a r a d ia n dаИг: гаипс^эПу.
CiEtete Ш Ш 1 - Ю .
651 W as -EM. Herknda. Cwe alien г пшншеЬ antjogsm ar>dranit d^esl r cctel с
slnaaslhi AnJ(B№ ainKi 1&7069^33-14.
632 ■J Qr t f i nO. van: 0 аэзб: neblcfa;^ siJled ^ Hitjess n атсссгар^
^ т я и а а '963 150:5-17.
633 Scad DJ. CT. HJ; D^V Fue^iiein stjce: у Та -el па с icuiili«i г cctel и. Br J
CtiithdiM 19б3.^7:53е-9.
63i Sn rr\s j К KwMsln Г Mjactei К kkperri'e a fun-la Inm«merL ii a lA lt fctnoativ.
CtMdmrfraj 1901^6601-11
653 3slram E. ш ! S, Fetisler S. FtelmsUcttjLMtn nme i' eiat^iea nelbu; tp e ' . 5r J
2pi!lh^m^l99l 73:-«2-6
656 -j"jar T. :ahiTJ. Kai er Ell. Lmg-tErm la Hw-iic j rons b tlm n datetes using Те
uluelichl emcflic pnensrieoa-. Ei J G^tbami}. 569:73.1-6.
637 Irm er T. ^ n a J. K'Dimer E?m fyroi; месжД' and d ifllc ralropattiv. В J СрП1пз1то1
159frr74:4CCH. ' '
636 Sricbf S i Min;j a-reli ct сj j i jf\ hsmctnna' is г dabrtc palerrt. ^Шз1тз1>^
19£l:56'3S0-£.
639 Iiifllc Fb :nqpadijf StuJf Fieseirch Gup A n >ilical м :(tfs Ariie H is a dassilcafian ci
■iaxb: гащн(1ч. ntissi ОхТап'е vis Sa 1ьЙ':?' 210-26 |Fjej:r7.j
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ciifili^e. Opltixlnctogica 13&7:l 54 151-K. eaema Oxitiaii'aapr 1£Ё&Й933-ЕС'.
74 i S an^iih p ЙЩ ja x it macu ar ederra ara a-ax iaser dcblocaagu alicfl: а ргафкйе 7м iilntf. GG Нзг JrWH. 0k M o ilie d gid laser ^filxsafletli'x !ir d^bei; тэ.\х eoema.
r a r t m i f f i d s t t it y Ep fc lh s im a xfl 1 ^ 7 £ :B 6 t6 9 -.-a . ■■к ehscl a1Te^rd-a visual lidd.GfllilTahclajy' &ES:3^:l Ё7о-9
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terapff йл JOptTlialtiKi 197£:8'.:83-£E. ■aaDetrelneoal-y. ^lliaJm ^xy l935;32:26&-93.
745 Ciafceic lelflopalfrr Sludy ^eiHrcli отар. :cu' ntk 1асш far seraph jal Ira m i ,'9 E!tinhen:hp Ш к rirical cxipa'iix d Knlral a^d кпрчега! згеоп aser pa rtia l
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l979:J7:65l-3. ' 730 Sarcner ГЛ1.EllerM, FnaeroTR i& ic l ci it swre macuir edeii a г е^ез virt" pxr vaai
74Б. Ha’ihc^/■W. Г^ньсепгаЧ gI danil>: reU'Cf-ify. “г э г а £kLK 1977;&7.Ц&4-й. a ic rffliflia гюкнэсшаих fcrprdls'al^ dafrin^ rehozcarry. &ае1к.й^тСкп ib
747. Haa.tesEL Gayecl. jLcaeSi-Etal Fe'itfera final ateix4nlx treatment aladreralr.-e
tiielic гейцнйту: a tree-v ear .nter n' repxl у a randon'i^d. ccfllrcled elJds1lan; tie 731 М 'Ш CJit Peawi Щ .ag^r JD el ai. Етепъе зксп aa- cnxcccajLla^i in ne
аип ice- & J OpTraixl 19?7;&1 :&55-63. is iT *!п; ^prtlfie'aL^ dchsi^ r-sir>:i:-alTr. Er J O x tam 19№73:1Э7-2(П.
T‘1&. Ttrcj; [f.Aatan;Ш ArcciiaiS'pTclKiaiaculiiix tralma l cl dash: cfstoc пхикраТу. TcC. li:ll Etl Metz DU. !-F.AugmHUatai cser fcr prcl fe'al« dзал : гзщаПг/ 1тз1fa n tic
% n^ № Jm ol 1977;9t3E&^2l e i^ 'c la nna pa'ieliial Xclxaacubi™. 19a2:K'.723-3E.
749. McDondd StiiL7H. Grid [fclxaacu alien lor dflLbe macu ar ейап а. Ftona' 935:5: 733 3bitenitip GW Ger-£E. ЕзЛ e J . t e and Diue-greei зксп dubn: (ипиша
Ш 2. tclxsacjitiliof. SfaelesAid- Cm ^СрП!тз1тс11ElfiS:2?7 3S^-fi.
76C'. Menn 5. Kinto L buy U Traarmenl у tintielic macu£paity fy a-qsn liief. Br J Sffuhamrt гЗ^ EreKJe'LB.Djejoeerijhn'ads твг ptiDtcsij-laingeiKwlh KHcJa1decennial of
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196ИВ:Б07-Ш 736 Li>]fem 6 Ездп M. tiz ia i A. Electcel r^prapnic Ihdncs v panielnal ptichmagualcn la
7E£ CfiJiE SioisFlft IferalealofifllxaagulaJicfii'ttienerapvcl artiierat&euabelic relroaath. ■jaDeteieinc^Ty iiaftJciriic aumhinuje gTeer aom arfradlepHilasaa &aefe
АттСрМтаШ 19E£:75337-H. Ajct Uln Еы CfNhantf 1SS&2'23 2J2-6
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rsnoDfolhi-. This Am Acad Cfhlltalmol OHar>ngeJ 1£72:76 33*-£. хьгех argai3nd -rpecfl 1айвд.Щ1ЭЙ^ ЮЗ-72.
765 Р ш э t o Ai, C-'igniH toi.el а. А сопншйне sal cf непх a t and agefl laser 733 ;ik ft.. Amsi cree i p!4 xK' Mensjs 'i’rpl'X red :5^7 nmi ncd fiec cr-.i aser plmoca;)Janci
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1932:6Й'3-3. 739 .^ijj El Airer Mwie Laser pcanoa^u'alien ocm‘3 cl d asfc n'acLtzr и dena. :Diai
765 fieeser F. :la;cm ui... ti№rcs jA. el X :Л щ у агшп aierбнЬюэдДОгн :n 11 iLO'eiahangM'aXv.B' J ^ihaJm i 159.7597-9.
теойгетсТ ciciile ciislic relrwatlih'.AriJ (frtharnd 1981 32:7a2-r. 790 AdariiAP. Ш- Jn мтэ) M-T. m^eaitd '^aacuar e^dclhatU gram ia^cf leds n Te
76r. S]dsr HF.Fmxaacu alien rcbnale m^cuopilbv iidafcelc rctiiKdhy.Am J Crtiinamal кЬ?яб Dl^jea-.^lh p-siieralrjecjlfllic relicpair'.:. A"i J ^ tra m J 199+ llEi:^45—£0
Щ й :2 4 2 - Я . ' 791 ШегзласА E. ^ e n ard daxfc t\t 'За ве G asfeE^ch Etp l^lhama
755 FE Tx ireaimert ftdsfiietic retrain*. In: GiDbeg \f. Fine SI. ethers Йррфшл 13SC:23S.l2-D-a.'
cn Ihe^alma'ld debeSt retinopat^. Ajfe(b^W airertofl;vigriia: ?itfic tea in 5&vra 792 31ЙПКЯ1E. fiUXemer 1 deJ u t e j t FjelbH пщетаЬоп yd laser I'saurem n pa:a'lE
P l i с л х N3 'щ ngta-. DC, 14ай. 'J.S. >p3lmail cf -eiilh. Ecucalicn xc V^lare ■лth cictn: iefj[>](.4illrf. Aim J Ophnai'id 1992:1 ■jl26-^.
Sefleidter^5oO[3cter 1 .1 Щ . j 56>^S. 793 Wti& JJ. ZLC^je ira i fi. The iV cexe ct tt;e рГс&ес^г-^Е дтр e? x d e nner elna: ar
7Б 9 . Ш ъ d d s HW i Hjeami M . F>^. el A H ie J a x l c m a ^ it ’p a t i s . Trant C p ir!-iilvd Soc sflaralicfl larineteiefciaJ riecl: z tftfxaoigu alien. CfhiltaJ-iBlxv 1933.27:1 'S3-9.
U-: 1Э7&ЭЭ31^-2й 79^ '^(мп it, Slela asx E. ^fcrnbers L Opl с dak nearaalaf^alicfl arfl relral 'jecsal dатэгег
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г й п я н й г c i i k a a q d b a tn n HednDcatw Slucb №RS| fiTcStga. C F £ r^c tu n u m lsr 79G \laflder .F. Cuker JS. Efersc^ V/E. Lxt-la m :laaHy an-dv ia l свисте alls' lajsraLfe in tiai
з . е р Ы ш &3i:35:5e3-*»j. ■езр'ХЖ a! islrieratoeaatKlE reliCMtfttic iLairelial phJl'Dfcnagj alcn. C-phnalTtl-^y
7K : Ciite! с 3ё1nafMltr^ Stud) ^eismch Sr-xf. TvK-jtif « j m -i vcl^I згигг г кмеге dab*: 19S1:9&’ 575-S.
КпвЕгай* reli’KCDCi^ * th I (яапажпй! >aslc Fjsn cpa^y Vfccclafc SiJdy 797 Зе'рег Al, 3a'ij ^.I. &lileral sijreliTal тесназсиЬпга! m аЛег fcal aiccn 'ase-1
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76Cl C iiel с isl n3faltrf l-litj^ -кезгеп нар. E^rlv niM niN 1вг даеге vtreotE tiaroTraji 733 jc j.g К i-djaxal AF. N airn' МЦ Cxicical i'e?^abcu'3[iiaiia,i one- laser p^DMc-эздj al an
:n dasfcretncfsTv ж - « а 'eulcrfa ran-tfl’isc lid: QaxfcFlekcpiTy viraclxv/ tordsfefcn^cuhrsdHiifl. Е^Ийт^ас1/ 199Э;Й-7:603-11.
SlJd^'repn 2.AxiCcni'EimcJ 1^ЁЕ.:.03.16^-Е2: 799 ш « №. Fran^. E. P u iij B#. SLCreli al ге^дассиАгсааап aller Ixj- argan laser la daHtc
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ran^ltrr а г^н :,it-LKlii мэх. reaitDfirankrruBJtrd-Dirac^Ifm caitiv £Oj Qu^r D l !J A ti» Du. Smrt;t^ Suianal ftrees alte-laser ftictxocgu^ilicfl In dnsete
'■^ire^cflu Eiud,r reportlOiMHliiitito» 1933:^:1 ЗОг-21 na: Ja ' edema Am J C^mh^Td 1W l' 13652-5
^66. Ciitei с ^sl nopals '^irecinv Slue-. Fjeax^i Ga^z*. Eir у TOflany fr fltditffjfa &Ol -ai CP Meler № Eulai T5 !!иьтзс jar It ™ ^attsr pholicx&gLtox fcr oatel с macJa'
dibelic reh cEltib 11 еуЧЕ hPi jKfi.1; s n . cln gI aDfl caix al remits -уз rand'^i'u’ec ей та: Алл J Oplrftairel 1992:1' 3:513-21.
tc I- >зЫ1с Feln^irh-repol I iM a n d p 1^Й:ЁЬ'321-34. & E lul eige БК Waiow l-L, Р^Ьа' GL Stt-aamect ealhsiel тетЬгж в alle-ptoTctcaj.liiai
7№. C iin с ^si пзра11ггtttrectonf Ehidv W34?. учИгефт saflre ^iTsctt !■! daxfc rr&itsr edera. AfX: OpTtalricl 1933:111.603-13.
remj'hage r Ciitel с 'el napollr/; li)J itar resuts у i гзшйгка tf:a: JiDetj? Fieb lcpaty &03 V*allctt I'L. 3 nde»-CC. rccal Xclxaaigu 3licn al l i t lie mxu ar edaia; a cEn K f alxbgi:
Si repel &. Ami ^hlTUmd 1 Ж : 1№ 955-E4. ■aie-ex^ Relii3.136S82S1-5.
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1935:1 C3f79G-aCHE. &Oj 5ctiau - MaceiiO HcDcfiaid ffl el X ^кц'нйеегЬгсетеШ cl ase1xaEdclJ.vra
766 Eaitf T'eii'flnl Iil^ lic F»iгцнЙКSlcd'r Рджг^ G'a.p. 'eatirem f e c i a i d cincal ■jricber Xcteaagualicfl lor dtftise dabe(j[::"s]?.lare<iemiAT:TCi:til,ialmcJ 19&l:'ffl:
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769. EaitfTei'j'fln: Jilflli: FbIicoqIUn-Shjitf FBsa^ Сгхр."ест+:jes.fcf :-:и^d j tcu dasfcrelixpary. MthaimDixv 19S7:£4:6'f-9.
diiftsicu alien V&rrM d ditel с 'el пэми’ц: -ari*Treiv*nl jaxlic РйИгср^;,' S in 1 607 I k s M Garer fr'J.Регртегз! гкпз! х д х а 1^cr s±iclsl иРвав remar'hxe. An J
repc[fnal!nl^](Hli3lmdarl937:27:2E4-6^l. ' CtMidmd1Se&.TQ5377-e2
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ара"жт W&j JAieI 1Эы£.48-ЕЕ. O rb r^ l 1977;BlDP53b-OP54Li.
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1033. Fielder ЭД. S ai; DE. Fjch паю I scol. r^alj i hsir^ -s r^iFEpativ ct peiran tv a 1-341. Wati Kj. -'г ш I TjpjGri' n EsTcdarmal ^ p aai аЛс^xht^ aTd с ehrc syrjerarre and
L f C ip e a jf e ilu J y . i'/e 1 9 9 2 ^ :2 3 3 ^ 2 . atalem' leliial dela^ma!4: Алсп Cptilialmol l Ш ' 11.734.
1031. Fleteier MC. В-акШ 5. З Д с al ргатаИшЬ j QpTdial rt 135E:4i:474-^l. 1342. K-JSTjerBJ. jlserkna i Fleiic^la hhTpasa r nl-lerni .-.fl culajpcare la
Ю32. Fr;i' J". Вгг^: :.: E.: xn. n:fc E^.ЙеКпарнщг у f#H tirFy dacflKe. seuatty. and Tjlual suoplai tfnla [£«pi. AmJ LtHhamoii' 93^:37.14S-i3.
CphГ^a^^>D^эo1,1937^4:E20-9. 1343. Rayxtfi .0. Hafjf ^J. Квптей1HA el al. L a i d еН ж ; cl igm 'sdicLm m p^'U^g
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hm ■90J- i(J 7:. О р Ш м Ш 137Э:а&1 Ш . 2 ^ m l ме G-xp ‘■ iЕлд 3\1x 1У й 335.1 *’ 2-*3 '
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OphlHbTBl 1377:Se.:217-23. nidaiiK cl mesWd геслэрш^ v pranalifcly. "■ais AmCphlhalm]! b e 2006.104:7£-&4
1005. Gavjp DD. Gc+dJ. Лйг-Эяй R. EflLai ca -yl>:'uh r as [txitls (ЖНеЛ^ ^artj n lie 134E. Ctm LG ^liaT <ii. Soa А. Саг евгдн n dhcalpnaci к CKtase ne I'cr^xe a se^re
[^ [г й г 'Ш Й т ^ я р г е т а и ^ .В г а i£9':75i32-4. reinapallrf crpfaralut/ r ffi.'vlmblih secM гйтз?Ресе1ла 2DCS'' 1339-4E^
1003. Glassэ. ■ллгг GB ^Ь-атп^н; КПЗ. Effe^ й hftjt I c^l ii tf^e xipls! ik ib e v cn 1x 1-34Ё. Saars JE. P ей.. Ьпэз С. el a-. A tttnoe h c ft^ i зxflerreia&x ыг dxrease Те
, n : ;d e n a у i d llH fa tt H 'r i pranalmfci NEng J W al '^ 6 S :3 1 3 :^ С 1 -^ nsdars c! 'el naaadv cl je'ialuirt^. OoiTa ifdcgf гС0911G:513-&.
1Ф7. Ка-ПЕГ fr'E. en PW Fj-jiaMi Jj. jagл : апа ^ s d n^ licm n caie reis'tJifrh' cl 1347. ftiV.li и -re1tma cl сг^отегарг^ br reir^pahy cl p'emaiLni; Fra irixrf -e:u a. G'ytihaiaft-
fjferrali ly. AmJ Oa ir-аrrc 1933:132:1 -G Я teiHialtrj ■ у FT&^nrr СсожгИгй Gicuj Ajch C^lhaiiftS 19&& 103:471 -79
ТЮЗ. Нег'Л [fcfli At. iliaoels С. Рй nrafpholoaal denkpmenl у ta hfan Ьлеа. 1-34Й. Rayxtia^D.foscc V Q ir GE.e! a Evccxe-laiedia-aenrgaile'tifcrrelixpatvcf
Cpheialniok)flyi9MS1:MM2. ' fftmatufitv: natud hбТогц'-йгй frcni lh5O4T0-RCPand J2KT-R0F Endiea &jch Jffillialrei
100Э. hiniSf VL FElralemil ih'Xiasa: OBpernlre Eauc^ cl 'erccnli! Itra ta a aid re ьм a: 3M2:iaft147Q4k
Я Ш tah ^IhUm a 1s e M - y 3 ' 1-34&. К .fir er BJ. Ussra L1&]Hei U. el a. Renr-]fiimJ ^fcfcpasii I. ^ c ta ic сата^з' ^jci
1010. Pdmer EA Gpl ira imng у earn ral cn ki асле retnclerla lih'iulasia. ф Ш йтаэд ф № т 1“ 77.й 23-35.
19S1jflfl(BE2-a. 1-35C. Cl ;te ftic a u - Малик-Скейте f,^. -era'cez-flias k,L ei ai.^ ayjaje
1011. Palmer EA F f^ Jl Кгг-й fil si ai. tindense ат- ea v caise 1 reilnepatw d :rema:'j Iv. ixra^rtttiiirl'^Tealbeftaijnabtj 'sinaaadit al яепаШтГц Fielra 2ССй?а^ц:р1|.
OpIrtHlfflolm1' 9i)l .99.1 E2&-0.
1012. SchJetunj irE.Fvemir I e A, Cf-n R NahjialNstury cl reli apiTi1al p:em3tLnri. El 3 1351. Rec^ia FM, Caxne 3r ^ Ocfliarpa,a,y undssla'dx; ai>diraiB^mmt ci 'el naaadu al
CphrKlmd 13fi7;J-::S37-«. aaralut^. FElra 2CC4.24 233-52.
1013. -asrim'ft.'ifteiecmiJ diixes nccaLxcl 'sfrtexaJ It™ aaa Trans {Ultulma Sc: 1-352. Marin DF'deienifrE Upflr^ftXiEieinalreGttacnnremt in stage GreliicfaTvrf
1973SB:HS-94. jranaluiy. Aren Cfhlialmol l SS2;''0 io3-4.
1014. "en%TL ЕсекиpremaULv and Itn i a^:miemnMicl р ечав:: г ш ,Ы sxali tehnd 1053. Bam tesM i HanidaiAv 13лс >lsc гхгаБоМ гЛm in dcmirenl Mjclalrje
e&^! a>stalie lens. I Frclimryrsfxrt № JUpTiBalrel t trairel imath: f a n ' £<399:27C-5
1015. Inlarтонна rarrnm In lie с asalcal an у ta ele tla-jes cl relfcpzTy cl p'smalunk. 1054. Bad'ey Ei Egaer P Gass JOM. el a "he йЕЩшНода r miriial аииса! к hfl'&aedxfitj
ап п1нлЕ№ла1с1шбса1кл al e:raxl^ al (Rm tun! I.Hisctssiialicn al ■£ra а герот у t * casas.Й1Й1 0a^atra 1930 103:23Ml.
cEtachment A 'J QpntHfeml 1357:l СЬЖО-12. 1-35E. Br&ixfsl F J . ^ h a n ^ a l x l M C IrdTosm la iia ejudalr^'Alo'einapalhy
1013. Ffefisi № . iji!- h s CG, Rii ^r EA. e! al. Tire insJerce cl IhiiiKBlaaE ш!егнег:х5 n AndkCpMBtanol 1BB1:9SL2143-6
c l:ij?' :.::i Ш i.eght lass Ihar '261 cr.ji's Rea;:: Ih'c.id: i>' 'SjEflia.С^сЙкл^ Ui 135Ё. Ca"i ■.C-_B. Cl мег Gl Ftc e^ef i innraiaiihc in in y r fa-^l a >trxrelr*Md''..
RHj>:cDL'r/ -DfFi-Eflalunry йкрнавге G'aV- ОХШапчо^ l&StruVi^l-,-. AnJiOphi'fllmdlSTBiW 1114-20.
Ю17. F^i ■JT. Aj '. iTjemilictEd aasalcanan cl mlscnitv cl шЕ-тайИк a n a l enre'ience. 1357. ChajLChai PR. AR Gcutn ne el а. :зип(и1 a-Lcai \t ьтткгепхрагу
Cchii]lmc+4V'®3:32:9fi7-9i. assxBlflj'.vtlilaiila ИтптйоцЮраИ^ E i. Op.ift-iiliil1933:E7:7&b-3.
1С66. Ога.;l' h.VE Утеряй CL Fa lia. efudatoe Mlreaiei napallrf Am J Opiiltaimd
196ЭдаЙ№тЙ
1069. E.. Wine^L.Cleaih- 1Ж Алоэяти rtminartairialNE vtoeoffliHBattntActi
№ rird ШИИ:1532-5.
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пэлткс Jsr imlicn. OpTtafc-l 197В:Й£.'6СЧ-5.
TJE1 &>v J. СЛrer GL. Fania efudaJta tftneoret raaaM ai еиатСеИ v ei,. Arch йrtslirai
197^ .86:150—5.
1062. Ucua H. -ami al ешаа^е n&Kretiicpatfiy. AlbiKfci rad Graels A'tf- Иг Eaji Озгта ira=
1S&O 213:121--53
1065. Мг.-акХч К Hesrimcfti 'I. № )A j Ih S нейф ж иЬг рв1Ш$ n femld вийШв
wlra-dincpaliN. ф И ^ таед 19&4:Й' :1524-30.
1С64 !.lf,iakJs К т л н к Н а Л л й Ь К FtednaJNmdvEment irc n n J эШ й№ ni- e? ^|>:сэ1тд
Шшго^ЭДВ5;1!5-Э5.
1«6 Sljsier МЛ knc-iWE Farid sjaiFje vttBaeflnopam^nJ Ортглгта 1Я79;В7:
1Ш
1066 Tain'ai W,АюЕбитн ll, ffikJfe JA, et al Fanflrf еяизпич ййвогейпсраш Т^тз Am
ОЛ-Talre See 1351:7“.2' -M.
1С67. «n Г.сли^в CE. Ekmtnav audafffi t irarelic cdfo and dher нззаза dew оркниа
fetfjfefstf the jenpieral И ла DacOa"thajr& ISfe;H :H 1 5
1G6&. ran Nojujs LE. Jlm ri e relra I (fctactum a: a ■э'фсЯш of famIol enud-jj-e
w tpx^patiy. гсга*г0рита1пс1 13S9-:at:221-3.
1069 Sv.a'Ea-D, 3uih ЧВгс.^С. 'teuil css тэп r^nd зесегд i autosaral damjiat audA e
mr&Dfid^pal’r,-. i!r J ODniiDtra-"S©2.0S?S27-9
1070. N ^ D hJ i№ № Affi ce ferxAL. Fluorescein araiamatiw n midsl&gescl dorttait
eeiUMUbEOTtinqMi) ModPrtti ^Uiatrna 1979 30:1 J ’ - 4
К Г O ir R1, Erd Al-. -^amiln .AM. « aJ ВДрага! й тгат: au ta re crrecreliTC-pat^'. 3r J
O r ta ™ 19Mfl4:l10-afl.
10712 IllfiTibafз Jr R Lc^ei P:. LarCtfl НЛ ecal. Оспгонф n Tfl тагорегсеи: cf reh краП'у
al xer -fllirfy Ал! J ОргеиЩ 19Э2.1' i ' 93-2C2.
1073. FljJIe- JA.AIi M GJamOF FtaA.eral Mutatire r TSWJ1£t£as&autoearakfcrj(Hit
laiila fiiudatftEvtranUiiEriJwflm J -u rn 6 e n e t 3 M l ; w 4 S - 5 3 .
Ш Fictnalle JM V^lice K. Zhaq 6 SaLftienolftic Dralapdlameslrailalife
hir&jsncfanf/fEflj i-.rr pe-aa.ei: ihalwscuaiu's prV| aused зу -№ m-nauorsm
p d w i F^.gies OpHulriicCeTel 2№Э ^И^З-ЗС'.
1076 хи CH. .и -. J ; ; j e D. el U.A ™ s ft- fain I al ew te te .-traii^woaltiy k lk J ?f
тикнгй. HJ"; ГЛ1 Genel 3CC61Z.1o£E-12.
1076. ':fiija 4 c;ia -cjjiiffsf:. D ansaM flal Itarel in :a i ElhaajalfiLiaiCflt fen;
^ rtc . FZC^l. QEfi3ie famlak^ifliirevuafelE apiT^.HuKi jan^:SOIi7.l2l:l;EO.
1077. ^пид Ш b-xda D, GcazsIk СЛ. el a-. Fcn'id « ic a l m tfa lu ard m tJa r Me
ft-icred г и т е nd.MdJil Semr0cirlalncl2i>3::22:e&-6.
1076. Kti^iai A t: R Kteflim A. el a;. Ислч1muatcn n FШ сете i l a Jipaiese p a b * wifi
laula ewistoevtrea'elfiKmYAir J 2lW 133^7C-'.
1079 T(H"fls 0. Csf, *y LM. fci-jcmtv H\l el 1 анinbai an tf a lam Ikus 1ЕЯ4: for la^:ia
ИИБЩЙШИГЩ ГЕ'Лу. Ш 'lit 2iViq;1 С:37-^2.
Ш Кклй h H. ^Gima K. el a-. rr ^ g et iFZD- iruliiaв n ряекз 'ftIf fanliil
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1061 Faitfli CXni C. 5tmK Ci. e! al. "he <xJa 1&iTc c?; a1Г-.cne 'iieas? mi aelui ci 11
.i B k i' g e s la ia T a la g e .G ia e ie s A fc h Q i ' E ^ O r t a ' i ™ 1 9 9 0 2 3 & ? 4 f r ^ i :
10S2 L: V, Fuimii'fl С Sc^opsE elil.ThemefcrautoDma^iirLflfamliiJeujcai'.e
hii'HrajTctalt/ itri^i-i-Schieiai я Фе Idtc am' cl ейш тш те 11. AmV 0ркГа1гй1
19921l3:rl2-o
10S3. L V.№le' Б. F i|№ n i -, зг al Tте аш нт^йзчпгП faialale^idshe ^rraneli cpiJhv
letjs cn 11qггс e -iDcel^ inrcd ti Cl 1S&33 to1J Hum jsnef 1992.51:749^.
ш NcTcfcoc OK GgLc i Cism-Srtspen; interne rtlamlial snealre Л т а й н ш й
stLfly al j C-]4a h ii k^Ce-d Ajch ^ lld m a 1J6 1 102:151 £-22
ш ?,iec[K£ CA.Fova: KA tin -C Fj"ilai cexkire 'дЩьтШфаttrj i^H-andftaelel
^sfun^y. Ei J Otfta ' 933:73:4У г-8,
1066 rti Г-.сjx is 2E. о ij!:i. comical ce. and Лзйе: aqgifpaliл il im'iial souiad re
Nil'fcfeti'Kcanry.Am.. OmTalricI l93l:l 1
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parsiilsr-ca cf lhe ^ may v.lrexs. а к.ч cin cal Entity? _ Fe-iaT On'irai ч1 Siai:i;(ru;
156625:77-66
1086 Beil\t Renliti F. -tef 'He "RseLtol cm' te ce1k a liienli! ctn'e in. ^in Mc^alia
A jqtfteM 1974.^9-32 '
1069. Elih 3. □pa'ltmi^e. hiitiar id ': 1ж±г е*л еэ стай Л еФ у Игйзгйтеш с рqmeial.
Stfiwec № с ^хтепжт 1£2£.Е6 ^ - Е .
1090 Ет™ W.liKiTlfeidafiqmenli tPedertspmenl si ш .с й с т а & JCftil'clmcl
1986.72:^52-6
Ш Cola аю PA inam reina jgmenli Ля1J Cfhlhilm]! l £S&.' 10G95-7CO.
т . FffihxiiR je ifc )^ lica fiienliificn'eT!. D f-exh'a^srflaniroajir
алвига rtet Ajn J Opirt-ahcl 1972;73:96M.
1093. F>Mel Щ jf-sir. m '.U. :,eiihile J5. el a 0:ctir; nl па: al rim re m jEpmedli p a
mae fllar vitli Kiisietn j (n J ате. J PeJ air ОртГ-amd Й 'а а з ш ' № :Й :1
ш Fmceactien A. JtidiSiST A OTfcs се Г ‘ifM lrenl a pqm&'ir. detmralu^ d; й л
я т г а п Е drle e'it: toirant sojs le mtne lernie DEmactgica 1Э54.1 C6' -23.
ш . fetijenq M F.C jalr]Fsu a andcttsr ni^ ilesliiia acf iTcaTmailtpci'ieni lEJxh-
£uli4'qsf ^rcram^. ODftiiaircBffr l££S'C015^5-64
1096 healicaeJu £схзe: ЕЛ.M usГ-.R krartinentiapun e^ :з с а & э 4aidi
obrpalhokbca Ira liH .C * Л Щ г Й Й 199120:229-37
1097 JairiFfi.Wlett; 03.Funiscliii ce; h ncainfdliipici^ eni (Hocii-3dztK(gerspdHre):a
ase герЛ. 8- J Cphlld^Dl 1£7&62 022-6.
W Kieji'H .au* „. 'Jeunalce'^e'a'ce-insn Da ncc^lrenla о^т£ч и lEtd’-SutLflnje'-
djTrtrcrri]. H ] r r | t i щ и hfiki 19711c4 '33-42.
'Lt+I LprQWA.Guerr:,-il D.FuKl^ctia:qs t iccciiienlB ptii e n iE^xi-SlL- sreer ff/TCJ-nrei.
A riJO rta rrs ' 95845:2£E-7l
1100 Median/ U JA^Smtti Л. [onjun'^d a"c (йнЛпш тш йа agmenii Лисп ^inamai
' 968:79:417-22.
1101 WeiGhSa-Maniar O. Fud'cuei Ip.SiddsJ^.eLal Fslralf+j^nl ^.liTeluin h
iTcaiflna'lii pi^'ieт.. Ш jtpKfalncJ 1975:7£.&7' -7.
T102 N^tma'a И OmY Ta^g I. el a:"nednic3l feiiresand bmtjrihitof the rctHgrtn al
Ehicii-Sn zta as ы j-ane Гго^йпяйн pcirsmi. Jn i J Олша n:c.' 330:2^,3l C-3
■103 Nк R3. A^4? СJ Fk: feialw leliTCjiity aa x al^d v.ilh nmlren: a pqma'U. Rani
ipi:M 5flr61
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1106 Smc JG F'BciraT ^l. C iile'i tt ei jJ. Ct Ja r ^aides i l iте EJach-SuHje'qer ^crom;
i}m ira itii р^тэй]. 3r J Cpiilldmsi 19E£-3927q-6£
1107 £са+эге A. Incchl ntnfla cgmenli lElacii-Eljlzsrcfl' мгйире!. seven теасг^з bm aie
lamlf & . Cdh-e it i 1 -K^-34.
108 Sjlnerce1МБ. ЬсогЬтепйарчрчги BtacT-su^ttrpen rapcrtal a-adilicflDl aae.vinh
сзпчгет са pasiU; rela: ci ъ a nw s^wan'e j ^amlial aic ялзепгл ггакк! ei. Ait.
Dsm acl3^ Ш :М :5?-99.
1109. totiise PC. Зоегеп^ТЗ, Сатеу J' F£. ^nnnf haiaJa dian^s cl i K^lreM a pqmsrij. Aren
0[№flhBi 1^7E:j 4:743-2. '
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' 96632:71 E-22. '
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J -umienS303l:££:l2':'>7. '
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p jp e if FletJia 139ft;'K M :
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la o i; hinctrtiitaidapigrentL FKlca 2LflE:26320-3J
ill-. Etiu'e'tiii i LcrsT: С Аяпзг? Ц й ^ т c^ercu: a asiix a: a isk жтег т дхсл
relml 'й п -Docjjijcfl. ft'i J ^fcslm a:' № 117:211-3
1115. ESennilen D\1 Treie Hjt^ramaiaBtoreawEala pi^err-iiicafcl reaflrenfe
ccfl'em.Fieira19Sa.'&&6i-£.
П16. ОайитЩ Лаг^зг msoilopafw and KwcJ-na'm nsiiU;eTia piqmend.-flphtHhiic
1117. Nealel MA. bnci J. Siul Г Й ^ e n e ace al 'el na a ^ a la ^ 11 а Гепйе rearale и fr
ncaifin?cttFiJ"flnl.. Fielra 2CC424 613-E.
1118. C_fic АЧ L l CC. Kaa ?. el jL in:cnl na ia pi^menli a1tnd c a ts lb a i m amd mca-
c a ir» k i*iM H ii Fulra 2Hi0t5O553-K'.
1119. Ralii J. -a>periaid J.Ea'bdaj'AEii al lie reh tp rkd i corUTenlc picireTd: ii>:tasilu
каП гщ ty c^ lh sif 8r_J Cfhlhilms 1£Ё& f4 ft 7-£.
1130. Скайпа R“. 1драутйу М. гатал Ш Tr^lmeif cl etc ilsrare 'el naлШ ; аасаагес *tFi
nca-nns'iii pigrenk ^jn J OpiTalricI 1ЭЭД:1107СП-2.
■ 121. Эгah ^ ^ula a G. ilab'S; F. et al. Garamc rean ij ce m\ ii NE'.IC irnni1:-NF-hzffa:
аййКп aid a a ca.ce rt памигеп! a aqmBrii. The iT-aralo^ ncTtiienla FVj^nli
Cixscnum Нш -еМ ООЯЗЕ^б^.
1 1 2 2 . Uaffeiffl Ттеайга^ атааН ^П е nevMia'csEcI OHHh I gbcaMlilix. C'emn
FtedotrJiejd 2&ffi?rt1S2-&.
1123. Desn С, Зааппвс A. Ftha H.eta. FOUiiT l т ^ а --and ffle t^ ic specftm n r"<.scle-
eie-tjai d seai J Med jener 303^:41:e115.
424. EtiraTVa cc de Berrab? D.Vqt T. Lofcran s al. f/ulai cis r ihe -genecai cause
ii:lec e-ftie-h'an d«a;e ire i>akr-V*a>jg spdmie. j MeJ Сете) 2C04/1 :-±i
'125. EJiew^f/. \l2r^ifi-№. Затвта"п 0G. el. al Musce-E e-Erandseise. JC ii
gBucmiisai В Д Щ 1 1:124-6.
1136. Denir E, Sus.^nef <,Aklirk А. й й Ат uiuibsf ргке тгаьа' cl mJscJe-^t-laan Sitae,
sereie weatremaitiawiti mid nu^M biam & M lrefBra hJecram^al
0QO9;1S:B»-5
1127. О-е^зй FK Wiai^blan M. ktare CJ, et a: Cram^епйй&т cl lhe LAfi2E lantf у
^ K ^ jiB s ^ a i± ia S s акк-азЫ м1т ^Elu^icaicaaBiies. Gv-ttiJK-i'
1138. Hil laclj £ Gtei 0. Senal Th. ei al 0 iiial iped'um a" nuaile-ftie-h'a n cease: ''а ч tfl
hp:a preienlnan-iere'saiUilic lEatim A&UjfD ^№:23:l37-9
1139. Sanls-ji.cn ^P-fihc H й п о к ela.ttLicle-efe-tmr ceease aTd^ter-rt'anu'g
^тсГлге.Аг! J Mea Gerel 19ЙС-:36371-4.
ИЗО. Metci'iM. tofd Si Mjs3e-?,‘H J2icii£S3'!'EE-. Згас Df'j 193C.l2:2fi
1131. ^ntauori ^.Sare1H.buiaK e!iJ. ttEcfc-ne braii aiffiseiME3i.6'ar D?:
'989:11:147-53.
'132. Railti 0. Lamnns W, SartartHfi P ei a. ^ h lh ilii» ™ ! гnd r^i с a new г^п^а "fl i .rr
iriisce.ejie antm r № * a v£nl.Acla Cpilhilma i^cpaihi 197E:E6465-72.
1133. Kni3fL He к 'JS.VJlaruyTJ el sUiHrkedftiskifDficas йиоятйа is predxinaittf
cased и mssar-se п'Шэсатз г. Ihe CKC1 -репе Ля' J Hum Sena 1993Й5:ЕС-Й
1134. Vuicm*' T. ttamaie й. Gadma; F. et a. Ihe ^№.аипюпеt c! letmsraK is n'clala: i
аийига- саипа-! а ^ е гтЛ:ег cxqe da. Naire Й01 ,h13:4^-5.
у +e 1135. Oijn'Kfi X S d n a OF.Ctja1luiicsm jfshersjticiii sftierra. Eilh DefecfiOrto Art>: Se1
1332:18:1 £7-74.
1136. Teto'a _F.5hecs 0.. Мэт E. ri ± 3 (a a i mlia. Mascucaaltn1n a paier v^lh d'piberalaits
KfgaTia.Ajch ^lldm ai 2CC6132:134-5
113?. Jofnscn CA Hatnsld U, f\J cc Fslra. щки toathy n a fan fr inti аийига flamnsri
(^анайвв cmgerita. GphEHlnk Geic-t £009 33:1 614
1133. Basler Ц W l» i '& tfasai PJ. -tystjeralos а caxei га. FEES Let: ЯЙ0 5$) 10:584:
3831-fi.
1133. Мэдо К 'ft Isai СВ Ееьйе1M. DyStaalos a caxei la - a 'is m ct ChYuiciaal e Иге e
гиПепалх.йпг Wot Мес 20C6.51.53-70.
114fl. EiiвегKJ.Ktsn.A Har>:i.к о т J.el a. Oxcola y vei_sara iisuai p'igpasis anei сен:-
resnal нйп KClii.:-iC4!. Але CpTtahwl 1953:21 Ш-7.
114B. Fu no T. Cutii 'Л. \ctten ГЛ j . Ечра i; ™ ccira relial wii « d js cn: j Ойпрайт cl
iM-aocjar ax edraxu oxlwiai Aren ^ lld m ? l S6&61 395-4Й
l U2. H iiilm Ml. Kjc-h'iif 3M Fosei C. scal. Efpsinenlsl *exus ахиаэт Ftk fi £к Med
1ЭМ Л7:1«И .
1143. HarifcnAlM.Kiofcm BA, ftisenD-, Яа 1.Е я н г н 11в1 reli'alterit '.тегосааа-т mesjs
ncntffb I Q ua] appeararras. 3r J ОЗла rca: '979$ 3J77-Sf.
1l4q. SS DflLiiMioi алеижтепЙ ял кз! lie cenlral recnal геп кйимг fa s
Ophnakinl SOC-UK1964]Н:51Ю-вЗ. ' 1154. Cuitai FH Ehian \IJ.
114S, H^Ter.SS.'.'sii -eifrir-hV^J.hUf^si':fhlS E<pei n'eiral 'Sira '.cscJa xd usicr.
Fmqeness ct ceclral ranal n каияоп. № OptrfiiaJmol 197Й.Ё631 1-23.
1143. U .ТпрзгГ: FJC АсПйп 4 Etpa ireral 'el na tranct: цйn acdu^x г *e monkey
tislaEllm jH lard JlrasTJClira-anles Tran; Opitohcl See UK 197630232-9.
1U7. taifcy D.Tnpal'j FC A^lcn W ЕдрачгегпЛ rt\rtf trartfren k^uskt i :neaus
ncntfns II HsiflitfjciajiMl andebchn гг!Ж [£ н 1 stuies. EWJ OotTfL^md
la ra s ia flM ii.
1143. hii-hoif ЕгЛ Doiony СТ. Siaki M, et a. Esps iretal lernal bmch ve p Ktfusicfl. Am J
Cptdokml 197C:6a77S-e25.
1149. FhtinDdnJi.jMHti;insuflсettcyfe;toma; «ДОфоДОш osfrrt щ п к )ш 1| Таи
C3phrnlnnl Scmt-UK1964Я4:БМ-в1.
И й . Keiner&..Faury ^M.Seiccn IC el i.CArDtnclerAaagngarterialbkKdl&.vm zenl'a
r«na van K[lU;Hi. -[йИигЛт^зд 199^:11': w - f l .
1m . VAl т от ~H.Biffir Gr/. 2етга1 ie li'a lin f ljs m. an nresttgatiai ff tctf С(мрн
|[Ж 11Сл t+xd^jHtf $ a^eislics ax pecdiai v iris п к ^ к JaiiEbDi!.
11ь2. Gas JEW. f<iSL-aiKcen щ ср’щек е щ 1cl irecu агЛ 1Д.1ПЯР1 зеозгйа.ч1lc relra
'Лйсиаг с к а к . I. Ftelvial ^an ctemdlcn. Anti O pnai'd 1ЭДВ:еО£йЬаЙ.
1li3. Gas j!№. Elsяо скг aim ct (гзсиЬг dieasea dticnaiia аь ireanienl, 2x ed. S: lais:
CVUiifry т . ъ ! к
1154. Guliiir FA. Ewlualcfl o' i рзпет win cental relzdfwifi tbtebr. CfMldioDtei1
1ЭаЗШ 4М ^.
1155. Ha^'ET: SS. 5ка1м Jsn!ra i '(йп KduiCfi.' 1 ?ве1вдеге1^ letunoiw^, dnica
neatjres. Optitalmokgca 11721-13.
1105. Hi.vrsr SS- Casriical cn ot мгис! isi ri \чг и и а х : OtO;a ire c^ 1£f!S90.£55-74.
Ili? . Hiysf ^ Э т п н т а л MB, F. nsaeroe d ram Bljite эГш а wh щЛенп
aod пег гезлгггй and dfemHsp с -:Ьегэс1етз1сб. Ah ^ O p itJiicl l№ :l 17.425-Jl.
IliB . HllCrt G'illlliaJD T^im raaBirednal ffirtt™txH£.TiaTsCdiitBlnitiiSac IK
l9^:3C:3£9-22.
1139. JafeL.GoliflHgFIc.MagaigaJL^dal Uaoibibrandi «hocdiam [|№а1гйщ[
l®3;a?:&l-a.
1160. Kctins IM La lia n ^ L.Ctchiai J Tie rraxc&'ienl а: сег=тг1 neira^r cccliann.
OptiriakiBlogy 19S3^1:4M-?.
1161. Laib-Ji^i ^ Кзт^rEU. FIjctescan ar^rap iy aid is aaomilic stgnlcaicB m'anl'a
leinal van scaiisicfl. -3r J Oftilhs/mal 1976.60:^11 -&
1102. ^ ie la L OtfBiaji; U. Laef-naad tfc'ioieti'el * я щ з’а^гаоз с п тыйтет: сг
nmsclHrc кг1га1 ra id неп кйижг. k f i ОрМхПй 1ЭЭЕ.1 -S:4i6—ЁЭ.
1103. Mejead С. ;Лч;е' ЕМ. И-и'^гтГлраз гтаг catral 'el иа'иг кс uex-. Cphlld^
19?9:ЭЁ.1Й£-.
11сй. Fv iin+; [\ FutKiti-oi СМ. Шlechast V , : , . . спз-fcn r lclsf.v-L-рal occJ.b cn or t t - a n r j
rana чйр ta ycux adJls, Am J C^hhaliKt 1Ж:20Г 90-2C2.
1165. aFittiW./SrlH^insutflnencvlritie^ wnctc coil_fl[i;i i|a sjrerew^ 'm s
Gptithalmai S x LK Э9Й)М:М1 -fi ' 1205. Elraai' f/J S ail AJi. 'j. i-iai PM ci ai. His гбч fcr sf^le^; 'jscu ar ceeaaes сгй ncratly ii
1lOS. Zeaira -. it ir a i FA, Zaiw fi, г al. Pinal acc naon cl tie Krtral 'кпа не п. An -
орйнышдезэо-7.
116:. MefflnsTF. Dnerenld ааепкв -тcatrzl "ei na' w ii cbslnc! ci 6pTiaix* 4i'
19fl3SM75-8Q.
1169. fleyes ^t. За^т К . Garre JW EiMd e« a :n itac Ja 1wlad spaces sre If ar rela: cisi p la
isnai van steluciHV Rel na 19Ё^:11 ' 4-i£.
1169. FasAJZ. Headon MR Hanln! AW. et a. ra'Bieni >езм m l sffiil iic :n acis reliiil vsn
ccd£iai3.Eu:1M?6.313-£.
1179. Нэугг SS f/aitf-Vi1,Fl'e cs CD Oujfer twwtaw ■■](сгм'с nelfal win co:ljs cn.Aici
CphiTGlnti 13те:£0827-33.
1171. Sata:ea R. Htnse T. \1cMeel ,’,V. Efedrareln>jact!i'm ts р тш кЬ эх с asilral cn of
ca tra! -e1na wh сния т-. Arci Cf hlhaJiwi 1Sfii -01232-Б.
1172. Minun J, Згспп 50. Fl h « sh i зг rcn эс1нг>; cestnl tcI ra re n aoalriiлап to lie
isciemic h^'nnl. Qptilldmaagy 198Ш:1?&8-е2.
1173. Wefcti JG. i\ugEtu gft il. hsisssrreil A anja ia ffc retrial caplan.' nmpejtuaon n ca lral
PMinlwn пойвЬп-.Дт J O^fraira- 1987:1u3;7fi1-6.
1174. Haph SS. Ш уи n ШШ, 3a: hi sccl. СгяеиНа&х cl всЬепй:iron-mn isd'em с ■snl'a
regnal van ac^uscti djrrc йвежЬай 1е chae G'aeHesAjchOJr Efp l*ihaJn>i
1993:22Й:2Р'-1:.
1175. Serais GE 1vn psti US, «ягёй SS. Зйа! w atietenl puaiay cfds! г ceriral i^rnai rt г
codLHtfi QptitfiflmiloCT 1966S3:M1-i
117S. Gret' Й1Б. Эм и 4 . FHitf i t aenrn aid rejaaw inerenl p+i ceffls n canal netna ren
щ и Euf J Cphlfi3jT>Di 19S-'.
1177. Ha^eiSS.hugnan MR ^зФа^. P^aJ.Elan'aisinacrafJvii canal ■esna ^r.
'Хс1^сп:соте1а&](- cl asclrctelrcgiaJ^ cisrgs ;:tf рид(а^' abTC<raJilies G'aeies
AjciCIn EraCfhiialTCt 1ЭВЁ.227 049-E'.
11те. Jbtah! M^ W efts Т.. EBarofetimgraiSic ^nd ngt n Iris гшня^атайсп djs lc кий
ciiral relral-jeinooilieGn Arch -^шэгтя 1993.1 H:S5e-U
1175. Granl WH. Sfalaw na ^ f t artericrdmtof lalaw nn -xajscn of tje кгага гейн1 «in.
AmJOpTfjolxl 19?3:?E:3£4-9.
USD. Hj -lLtb i'.V.NenianiE.T'aiscrdai-flle-dBSjrBcJaLC']!^ sneriermaj лп к^иь*зг. 3rd
iflllem ji 1&72Й353-Е.
m i : Weber RA, ^cisc JS Beks ’■.D.Ca lral jelna ^rccckt^icn-1 та№ М ейижгаз toh
;ftilli;;ma'!“£.7.'iJ3:ji33-0
1 1 5 2 . fiasco С. ?агл kfi.Ejudatwe reftaJ detachment SLdseajeM йгейпа! №n гаи эх.
(Ш й п к Ц и Ш Ж Т 7 -& .
1 1 8 3 , W ate га и Ja ift LM.Sotiazh. Sal Еиййв1^1^адфп^1ойш гд cenlral ала
leraca'tfil 'el na: w r c k ^ t j . ^cn ODCJhalrtiii .990:1 M:27' -5.
flK, fl al. the nabmi ooliss cl tenlral rennai re п каш ™ . Am
J0 rt* * ia t 1990.1 it.I £-23.
115Б. ЧЦ^в F^ SocJui [l. Oenfa reUul vein ocdjsicti fscfle a^ec 4C jiecfs c les::; awifu
ot :7palienlE.3rJ0]fttiati4) '^3:7^:3C-S
1Ш. Zecsra ti Gjyan Octriala J.Therjlu'aioirsed snlralreanal'fan Kausw.
flp fa ro k w Ш В Й 1 931-9.
1157. ChK-CC. jhe tt. nireqjersjctrelnalnecnasculajizaUintettrwrq Knlralr«nal
oodл cn. CcnnanKtoqi'' 979:55:2E£-02.
11Д1 Hjf’iel S3. R]cas ?. Pocna;sfy P. ct a. O^tr re:waflcu arizaiai wlh iei na: mcscJa r
oc-Uj;cn. II. пайегк d xu a1nec^uscia'ahу Viili rsort! ,e г ^Hiusti W itfrfm d™
l353:St.4&3-52£.
11-55. ■.'a^gal I . EiX'.'.t GC, A jciticcrJ,. e^al.NanaxilargtiucanalDkr; rgctnl'a retnel
■hn'isfirjclicfl. З^МапЯху 1Э51.62:' №6-1 C-l.
1191}. S naa r SH. SfiicaШ K . arMX3s H" n.C«s a n>di Шмид snlia reinal vesnxauicn.
3rd 579j63 735^3
1191. Atooi J, |щйа M KaKelaii A. et al. Rde cl tx ^ir&ir. ш роегегп' seperi
x tf^ ilan ia: ci ;n anra red nl van -xil.scn. CpIinaJiic S jg 1391;22498^502
1192. PdIoch.A. Dorian £ 0 iva M. The 1е1ал г/е ii retinal <t n actiusf^ dsease. Qftlia rro
195£:5e.E42^.
1193. D ft"fila ^ l.lcier r.R F neS^ slai.Theehe'Hc! xe a t i flci *^ a o .ik a iT e ^stenlc
^idvejel jregiaferfcffiiral w a №a' ca: .ж- Aust UZ_ Ср_,Тдк"й1 l93l:i£:l '£*-22.
1194. fiuansle n К -jenea EB. Raiel van x d jst-n: iDxlem p'aspeclb lei ^eara' ct
143 paJtisfa.Br JC p h ltn ti 197Ё:Ё0.-^-ЕС.
1195. Hunter M. Л tfp : 1R. et a. Faal сiism a ard oiet ейг с с с Ь л In j ptegiart
woman. J [I n hta.roSpttTDinna' S0212226-9
119ft L teK.^tMrK.Fjcli'a 'кяска 0 jCphhafd 1951:46. i :3-^0.
1197. Йпнрнп JMS.Ode JG. Е^ча'е kW elai.La'gecflic nerNf.vlr central retinal arleft ax
vBsnoKJjscns iretn ap^B r^jns.]periia;nlc 'alierl'ari Ijx t. J Qn НешЯЦйаНтй
1994:14:'67-9.
1Ш. Ci=KerJ£,Sef'Jctl:RC.Sa-:njPd.etal Optc Teurito wtti m rcian ieina \tr»xislaL.
:^4ilhi;n»3cv 1939:56:475-50.
1195. K?Hef 3J НзззАЧ Relral 'лааси ar ctssase г d y a l # Ed fe. Ал1j (№йтйn'c
1394:116393-Ё.
m . FcmACO SciaLTH.?..V:I'cna;d -fi e! а. Секта; rek a «n cccb an n vxiflaaillL
jpaplcpilEtilBi R ein alS1 113-1 т
1ЯП. Green № . Criah ОС. ralchiTS Ж er al. Central ‘etna: ueh ccciiam а ргф*йге
istm atf3ycslit^d29ej4sn25'asfs 3s!nal93l.: 27-55.
1203-. Apaal'. ^ (Jetridge C . Pdil'XS к о ж а ж Г (eliiclvein codja n n hjpa'is.
SfiilMmol W ;l9 L3 0 f-ib
1293. Араз!' № Тчтое CL 3isK гашз assacianed w Ih crandi ke. cenlral r«nal vein KEiusHi.
Щ0р(йи1пи lsfis.?' 153-7.
1234. Brane^l iSccrier D.Ca lraJ ^elna Merifltciiaa-o> "dcalii^sxnlar-eajS'a.Tdc-
^ tfia jE hEtLH А"С1 GptrtHJmd 1967.' ffi -'-0^-5.
DarienlEv.ilh'STral rflhal*in«xkEim.CiMial!iKiefly 10S£iS7^S43-S.
1MB. Girrc G .^ n W .T K ^ M.eta 0^-tTe-caj,lerj:tH'jlpr3]eit];ai(in-.- a x a tle caise
ot central шпз reii ncajjtenAfliiCptfflHJmcl 1966.'-04 042.
1297. Glace: Ben arc A. Ztistansl A. Casas G, et ai Еш1 cn de Гзогесазз! еп е н кр re au
coxs ds xdusicf s rereusss nelnerties. J Ft Odtalxl Ш3:13.бОО-i.
1m Hnh ngs F^. ibaeT- GL. Стопе netiial ^an ocdjsica г айопй. Ei _ OpirT-ahct
197Ш Й4Л
1205. da'^eraen JS.Gjlotl P. Ojfltafrcscqx li'mcain sp-aiaoecu: cercwca^nctislisliiti.
ai aiat^ts r23 libectL G'aetestoch n Елp ^ilhamcf 1968225:34-6.
121D. K-Dtiner EM Oafpr JM Dj r t dcal cendtionf Пане tn rllu ais on сына; relir-al w l
js cn7Pmc з sac Mod 1974:67:10524
1211. K'ifjef К.Дгдег V Hass D. >r Тгю ^brhfldf-tiarim-1l-Kompte* Ursaitia k i и ;с:е i
■^l35S№iachLsen d?f Hetrhani 0]С-№апчаде'992:-в9:Е7-г0.
1212 . h'iarst.: AM, '.Vasi J6. Gcti^'ga 6. et al Rcle cl djitfes ire;ics cn lie na!ja: hHct>•?
oiiral reUal^nculificn.CpTlolrttcfliLa 1992:204:57-fif.
1213. Mc&at.^tt rt'schslet F. Кпдо AEl.etal rKtcra cd ii culXhtu relra w r
■xdjs cn. M i i-tcm Мей 1978:136:216-23.
1214 fiar.EIiankfihJ Slii' Dh el ^J.Fls-ilaiifi'aijf regnal ^na^ustDrs aaase-ccnl-ia a w .
С^Шгтк(вд 1992;59r509-14
1215. Rsss Ri-issilM 1жз H CiiijlandeteclrajinfitsicJMica «Her^Lflns rpaljenlsHitiktt
aessuie 'slnaMlhh1Br.O pitiaixt l956:7!i.66l^.
1216. Sdira d D. 3chjroij-fl r M. 2eitraNflerrfersa1us als -cte nai sxrla'en ater frexsen
-isle n net A le ii carctE mm Snus cat h'chje. Fcrstt Opifo ncl 1991:5fi:665-0.
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 KfiJoM rtrct'.va HYasncaA Rdeal Ihe'jilreojs г reUJlrjejascuahz^aievaLaled
b; a xrnpa sen г секта relsial 'т ccclisjn ard агачп rnn^ ген эойиног. A:ia Sx
СрМпаЫ-рп 13E&;9S&l2-£.
1292. KatoM iremDtC- Fi:le d1Tk Mrt'frDLum згвгст rsrsnsJ н^п ккаи&зл. ^ti ^ Сртз а^й!
1935:1 C5:20<
12 9 3 . T r a ip e i l . T a K e l m №. fo p io w -V i . Vfcecus с т е л ю in re i f a hraicfi re г « с iisfcn
О р Ж | г т » * о у ^ !ЙГ1 :ЕШ: Ш - 7 .
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Macular Dysfunction Caused by Vitreous and
Vitreoretinal Interface Abnormalities
Diseases affecting primarily the vitreous and vilreo-
retinal interface are associated with a variety o f i m c i i U e
lesions causing loss of central vision. These lesions may
be detected ophthalmoscopically and bio microscopi­
cally and should be differentiated from the other causes
o f macular dysfunction. Jn no other area o f macu h r dis­
ease is the use o f a fundus contact lens more important Lo
detect and define the anatomic changes. Recently intro­
duced techniques that imp row our nihility in this regard
are optical coherence tomography ( O G ) and kinetic
ultrasonography."' 1
A N A T O M IC C O N S ID E R A T IO N S
ihe vitreous is a semi solid gel containing a hyaluronic
acid network interspersed in a framework o f randomly
graced collagen fibrils, ihe framework is most appar­
ent histologically in Lbe region o f the pars plana, where
Et is strongly anchored lo Lhe ciliary epithelium in an area
referred lo as (he vitreous base. In te rio r to the pars plana
the concentration of collagen and hyaluronic acid is great­
est in the ill-defined outer part o f the vitreous gelr referred
to as the vitreous cortex, th.it lieu along the inner retinal
surface. The collagen fibrils., which are condensed to Ebrm
an outer layer o f the vitreous carte*, are adherent (o the
internal limiting membrane (]LM : basement membrane,
or basal lamina of the Muller cells) o f the retina [Ngures
7.03 and 7.0.11 The basal lamina thickness increases from
the vilreous base posteriorly, to where it reaches maximal
thickness at the crest o f Lhe foveal clivus. from ihere it rap­
idly becomes thinner, reaching a thickness of 200 A or less
in the foveal center.l1>At the margin o f lhe oplic disc, the
basal lamina abruptly thins to approximately 4!>0 A, where
il covers the disc surface. Here the basal lamina is associ­
ated with multiple gaps associated with glial epipapillary
membranes thal are probably of developmental origin."
Attachment plaques or hemidesmosomes are evident elec­
tron microscopically along the vitreoietinal junction in
7.01 Vitreo relinal allachm eni in lhe macular region.
lh u ВЬНЦвд Shaking up thy vitreous i ог1ек i.vi ■
а о Ш Ё г п Co lhe internal liinilii>n membrane ibasecnent гпвгл-
Ьгапе of M uller cellsh- This membrane is thick in [he perL-
fovejI a re a liul gfiKlremely Lhin Ln lbe fove^f fegior. A r ru w
in d ic a te v fte o c y te I v inj^ on- the internal iimilin^ mombrantf
л I the.1 v iI neuic-Li mi I interlace-.
7.0^ Vitreorelinal interface al lhe electron
microscopic leveL
Thy dojlagen fibtfHae m^kiu^ up Lho vitreous cart-eX (vi ■^ft?
ad h^ ent lo lh e basement nif'jnbrane fbm, b a s « lamina,
iгИ(?гплI limilin^ mernfirancji (]i lhe Mu3!er cells iM ;. O n sepa­
ration erf the t iLrct] the ооНлдеп Jibnllae realign to form
Lhe posterior hyaloid membrane Iphm:-. Some of lhe vitre-
dlis cuftex lnjiv- t e n iin adherent Lo lhe basement membrane
(a rio w l.
(he peripheral and equatorial zones but are absent poste­
riorly except tn lhe foveal area.10 These findings indicate
greater adherence o f the basal lamina lo the Muller cells
in these xones wilh attachment plaques hut do noL neces­
sarily refect greater adherence of lhe vitreous lo the basal
lamina in these areas.|J ihere is olher evidence, however,
lo indicate greater adherence o f cortical vitreous lo the
basal lamina in these areas, including Lhe cenlral macular
region. ^ 1' Trogressive liquefaction of lhe posterior vitre­
ous occurs Wilh aging, giving rise Lo a lar^e optically empty
cavity of liquified vilreous in the premacular area, referred
lo as the premacular bursa, or prefoveolar pocket [E'iguie
7.03).'■r" :'- the thin layer of the posterior cortical vitreous
gel lying on the inner surface of the macula is not visible
bio microscopically and the anlerior interface o f the burea
may be visible and misinterpreted biomicroscopically as
(he posterior hyaloid of the separated viLreous.
 №1

51101}t?J2pi*11ДJ i _>lШО-JUUу
 The degree o f vilreoretinal adherence varies with Age
as well as location in lhe eye. O CT illustrates the change
in the contour of lhe vitreous attachment to the posterior
pole with. age. children and young adults show no Sepa­
ration o f the posterior hyaloid from the retina] surface
(i'igure 7.04D). i-'rom the fifth decide onwards lhe pos-
Lerior hyaloid shoe's a gentle curve away from the retina,
stiEl being attached to the fovea and the optic disc (Figure
7.04h, arrows), There are no visible effects o f traction on
any structure al this slage. As the posterior hyaloid tries
Lo separate from the retina, various configurations occur
Ш different eyes that include incomplete separation with
residual viireofove.il or vitreopapillary traction, and anom­
alous separation with viireoschisi^ resulting in epiretina!
membrane and full-thickness or lamellar macular hole
(i'igure 7-05A-E, С., 3, and ]). A normal vitreous separation
shows the posterior hyaloid membrane separated from
Lhe retina wilh a normal foveal contour (Figure 7.04F).
Generally the adherence decreases with age. ihe attach­
ment o f the vitreous Lo the retina is greatest at Lhose sites
where lhe !t.M o f the retina is lhe thinnest (I'igure 7.01).
Jhese sites Include Lhe vitreous base, the major retinal ves-
selsr the optic nerve head, the 1500-|im-diameter rim sur­
rounding the fovea, and the 500-|im-dianieter foveola. Lhe
Eailer two sites of attachment are probably important in
Lhe development o f idiopathic age-related macular hole.
Forces generated by movement of the vitreous and (he
ptentacular bursa as the eye moves may also play a role in
Lhe pathogenesis of posterior vitreous detachment (J4'D ),
epiretinal membranes, and macular holes (Figure 7.03).
7.<13 Diagrams of vitreous structure in old^r adults.
A-С: O p L ic a lly e m p ty p r e m a c u la r bursa, siles. o f m a x im u m
vhreorcH inal A IIa c h m e n l ila rg e r riTruwu indicate? g tB a te t
a LI rifh m tin l I <md d y n a m ic к □( vitflfiBus m o vtm H jnl w ith ^azc1
left Lind right '.И Lind C ).
Kishi and coworkers found anatomic evidence that
the prefoveoEar vitreous corteji (PV C ) may be focal3y con­
densed and lightly adherent lo the inner surface o f the
foveolar retina. 1 'iliey examined 59 eyes with sponta­
neous ITl^ with scanning electron microscopy, in 4 4 %
of the eyes ihey found three patterns of vitreous rem­
nants on the surface o f the foveolar area, lbe most com­
mon pallern, type I. found in one-half of these eyes, was
a 500-p m-diameler disc of condensed conical vitreous
adherent lo lhe foveolar retina (Figure 7.0ftA), hi ЗО^-Ъ
of cases (type 2) a 500-p m-diameler ring o f remnants
was found adherent to the margin of lhe foveolar retina
(Figure 7. Oft Li and Cl), lit some eyes Lhe authors also noted
a I 50Q-; m-diameler ring of vitreous remnants at the
foveal margin [L'igure 7.06А]. Twenty percent of the eyes
(type 3) showed a pseudocys! formation consisting o f a
focal 200-300-jim-diameter disc of contracted vitreous
cortex bridging the foveolar area. Ihese findings suggest
that the structures of the P V c and the vilreoretinal inter­
face in die foveolar area are probably different from that
elsewhere in the macular area.
•4--- Gai€:eft Обе-bricfiL --- &
 The cells that arc part o f the normal vitreous are
widely scattered W lthin the vilreous cortex along the .sur­
face o f the retina and ciliary body. iTieir concentration is
maximal ihe vitreous base and near the posterior
pule. 'these cells, termed "hyalocytes/ show phagocylic
properties, ba№ a high metabolic activity, and may be
responsible for bolh the formation and (he maintenance
o f Several vitreous components. L'hey are probably mes­
enchymal celts with macrophage-like properties. When
properly stimulated, ihey are capable of cell migration.,
proliferation, collagen formation, and membrane contrac­
tion. lhe membrane contraction (collagen) may be medi­
ated via Lransforming growth factor fUGFJ-fa since using
anti-TGE-'-fo neutralizing antibodies experimentally can
block the contract] o n . I his capability o f fibrous meta­
plasia may supplement the process o f collapse. condensa­
tion, and shrinkage of the normal collagen framework in
the production o f pathologic vilreous membranes. Much
o f the posterior vitreous becomes liquefied by the sev­
enth decade (synchysis senilis). This process o f syneresis
may be accompanied by spontaneous separation of the
vitreous cortex from lhe retina, a process referred lo as
PV D .]Q'3^ E'ollowing vitreous separation, there is con­
densation and realignment of the collagen molecules com­
prising the ouler surface o f the cortical vitreous to form a
dislincl membrane, the so-called posterior hyaloid mem-
braner which may be visible biomicroscopicaEly and his­
tologically (Figure 7.02J. EVE) is present in over 2 5 % o f
persons by the sevenlh decade and approximately 6 5 %
by the eighth decade, il is more common in women. PVD
most frequently begins in the macuiar region following
spontaneous dehiscence of the posterior hyaloid near the
center o f the m a c u l a . " 1 Et may, however begin more
peripherally. En most patients separation of the posterior
hyaloid face from the retina occurs rapidly and smoothly
and may or may not be accompanied by symptoms o f
pholopsia and lloalers Slit-lamp examination reveals
7.04 D ia g ra m s h o w in g stages o f p o s te r io r v itre o u s
s e p a ra tio n .
A: Tup, Vitreofovea: detachmenl. A rm w indicate*; crjnLratted
rind bdlidensed pjofoveolar vilrutws cortex.: [MKudtJ-operc и I uni.
suspends! on the posterior surface (amowEieads) at" lhe vitreous
ctnLical gtl.
B : M id d le , V ilr e o m a c u la r d e la ch m e rtt. th e posled-or h y a lo id
(arrraytlftad s) is s t p a ^ f e d from lh e m a c u ila Eh i I not 1lie.1 op Lic
disc.
C: Bottom, Roslerior vilreous delachment with hyaloid
(arrowheads) separated from the retina and optic disc.
ArrowH indrcale prepapMlarv condensation rin.ii.
D and E: GplicaE coherence LomarjjfapEKy o f a 40-year-old
wom an w ilb intact vilruotih com pletely filling lEie vilntxjus
Cn3viLv With iLh posLerior w all Abutting Lhe relinal surface, (D).
A 50-year-old woman w ilh early signs o f preroveal vilreous
t han^ei, that makes the posterior Eryaloin somewhat taut, and
it Eiegins I о sh-ow as a convex bulge towards lEw retina, (£j_
Fi An older paLienl w ilh complete posterior luvaloid separa­
tion LhaL is -seen freely EEoatinjj in fhont of Lhe ruJinn liirroW .
anterior displacement of the posterior hyaloid membrane;
A gray-white ring of vitreous condensation (Weiss ring)
l hat marks lhe site of previous vilreous attachment lo the
margins o f the optic disc is usually visible and is the single
most important btomicroscopic sign of posterior vitreous
separation from the optic disc and macular area [E-'igure
7.(14]. in cases where the posterior hyaloid face tears near
lhe site of attachment lo the crest o f the fovea, a similar
condensation ring may lie in Его til o f the macula (E-'igure
7.(16). These condensation rings are often distorted and
iwisled. [JVL> usually occurs without producing any visible
alterations in the re Lina. As the vitreous separates, traction
on the inner surface o f the optic disc, along the major vas­
cular arcades, or near the vilreous base may occasionally
produce a focal inlraretinaEr preretina], or diffuse vitreous
hemorrhage (Hgure 7.07A and B ).,a],iJ
 ?5eud:-openojlLVT

. i ,

If
V
®

Л r ' f ' n г-71 Г - Л Г п п П П П рп-Г-nq I7P|

■ 7 V
(s

Pnepapillary ring
 PYL) Lb the primary cause of peripheral retinal tears and
rhegmatogenous relinal detachment Pat ho logic alterations
in the vilreous gel unrelated lo aging may be responsible for
vitreous shrinkage and premature PVD. Patidflts with high
myopia are more likely lo develop V\!D early." Anomalous
$ fD may result in either vitreoschisis leading to macular
hole, macular pucker or diabetic traction detachment (see
next section) or partial (incomplete) PVt) With residual trac­
tion in the periphery c^iusing peripheral retinal tears, Dr1i in
the macula causing vilreomacular traction, or the oplic disc
resulting in vilreopapillaiv traction.1''
Vitreoschisis
Posterior vilreous сопел is composed of lamellae run­
ning tangential lo die H M . 'Ibese lame Ihe are the site o f
potential cleavage when the vitreous detaches. Anomalous
I^ D results in vilneoschisis whereby a split occurs within
the posterior hyaloid leaving a membrane adherent lo, or
in close proximity to, Lhe relinal II.M. Contraction o f this
membrane may result in anleroposlerioror tangential trac­
tion al various points o f adherence lo lhe inner relinal sur­
face {I'igure 7.08.A-C). lhe pathogenesis of macular hole
and macular pucker may be explained al least in part via
this phenomenon. Uyalocytes are located approximately
50|.m from the reLinal surface within the cortical vitreous.
It has been postulated lhat the split occurs at different lev­
els in patients with macular hole and pucker. A split pos­
terior to the hyalocyles is likely lo play a role in macular
hole formation where a thin acellular membrane is left
adherent to the ILM. '1'auL contradion o f Lhis membrane
over lhe fovea likely pops up the foveal depression which
7.03 Anatomic changes in the macula caused by
traction exerted by incomplete posterior detachment
of the vitreous.
A: Transit^ тасикн dislurLion. Arnm- indicates Ihe area
where1 vitreous remains adherent and is exerting Iraclion on
the rp4in,i.
К: lJos3erioj vilrtioui dulachmonl is complete. N<jle rarefnc:-
Li(]n cjf lhe poslermr hyaloid anIcrior lo Lhe foVeal area.
C: .VliLcular Iraclion.. edema, de^enermion.. and detachm ent
D: l^Lrnmacuiar Unction, retinal vessel avLilblun, and relinal
detachm ent
E: .MacLtl ar hole.
f : luxM papillary Iraclion and retinal delachm enl.
may cause a dehiscence in the continuity o f the foveal
tissue, initialing lhe process o f a macular hole. A split
in the cortical vitreous anterior lo the hyalocytes leaves
behind a thicker cellular membrane on the retinal sur­
face. Hyalocytes stimulate migration of monocytes from
the circulation and glial cells from the retina. Cytokines,
platelet-derived growth factor, and oLher cbemokines stim­
ulate proliferation of these cells, resulting in hypercellular
epiretinal membranes. Uyalocytes are also knoivn to cause
collagen contraction, resulting in a pucker. Recurrence of
epiretinal membranes may also be explained by vitreo-
schisis wherein the anterior wall may be removed at sur­
gery and the cells in the residual posterior wall proliferate
and contract. О С Г is able to delect ihese membranes and
their interplay with the retina, except when lhe mem­
branes are extremely thin. ■'
j гд,ь'ло ц sxfiTQ jixuajzjjj у
 Two disti tict clinicopalhological features o f membranes
removed from eyes with vilreomacuEar traction syndrome
without obvious PVD suggest different form.t o f epireti­
nal fibrocellular proliferation: (1} multilayered cellular
membranes separated from the 1LM by a layer of Interven­
ing native vitreous collagen In eyes with visible epi retina!
membrane; and ( 2 ) single cells or j cellular monolayer
directly on the ILM with no visible eplretinal membrane.
The predominant cell type Is piyofibrObla3t that contrib­
utes to the contractility, in botb types. The higher number
In the multilayered membranes may explain the cystoid
macular edema and progressive vilreomacular traction
characteristic o f this disorder. Overall, It appears that the
Eocalion of the split in the posterior vilreous cortex and
variable cellular proliferation determine the nature and
severity of vltreofoveal traction and eplrelinaE membrane
formation.
V IT R E O U S T R A C T IO N
7.0Г- Continued
G and H : This 78-year-old diabetic wom an complained of
cenlral visual change and difficulty reading for 4 weeks.
Her vision dropped from 2СУ20 lo 20/40. Ор1клГ coher­
ence tomography feveaffid focal vilreotovcfll traction causing
foveal cybts that did not spontaneously resolve on observa­
tion tor 3 months Л para plana vitreclom y resolved the
m acular е д Ё т а л п сI vision relum ed Lo 20/20 fH..
I-L: 1hiы 70-year-old woman's; vision decreased Lo 20/40
and 20/50 respectively. Small cysls in bolh foveas were seen
secondary Lo focal vitroofovea! traclion (I and |). Absence
of sponlaneous improvement wi'lh continued observation
Lot 3 monlhs in lhe rrgbl eye and 9 months in- lhe left eye
prompted a vilreclo in y in both eyes,; which resulted in resto­
ration of foveal contour and visual improvement to 2(V20 in
eaCh uye fК anti t ■
.
7,06 Vitreous remnants on inner ret in at surface in lhe
fovea following spontaneous vitreoret in al separation.

M A C U L Q P A T H IE S ____________________ Л: S c a n n in g e le c tro n m ic ro g r a p h s h o w in g !i00-|im -diam eter

d isc of c o n d e n s e d v ilr e o u s co rle x (w h ite a rro w ) adnferenl
Changes in the vitreous gel may cause traction on the reti­ to fo v e o la r re tin a. O p e n a r ro w in d ic a te s 13 00 -|im -d iam eter
nal surface and macular distortion through several differ­ ri ng o l vi treo u s rem n a n ts at the m arg i n o l lb e fovea I ret in a.
ent mechanismsr including; f l ) incomplete IV D In which B : S c a n n in g e le c tr o n m ic ro g ra p h s h o w in g 5 0 0 -p m - d iam e ler

the vitreous remains attached focally to the macular sur­ rin g oJ v itre o u s c o r tic a l re m n a n ts (w h iLe flrt& w ) at lh e m a rg in
of lb e fo v e o ia .
face, resulting in macular cysts or macular detachment;
C: H ig h e r m a g n ific a tio n ol open a rro w show n in B.
(2) anomalous posterior vitreous separation resulting in
N o te a lie n e d c o lla g e n fihers of v ilre o u s o r ig in in con­
vitreobchisis with continued broad fovea! traction causing trast (о s m o o th a p p e a r a n c e o f u n d e r ly in g in te rn a l lim itin g
macular cysts; (3) vitreoschisis with proLi feral ion of the pos­ m e m b ra n e .
terior layer into epiretinal membrane causing macular dis­
-I N j r n K u h i й j I ')
tortion; (4) vilreous gel condensation and shrinkage caused
by Inflammatory, vascular and metabolic diseases In the
absence of hyaloid separation; (5) complete IV D with sub­
sequent epi retinal membrane formation; and (ft} a peculiar
form of traction jnaculopathy that is related lo focal tan­
gential contraction of the PVC, anterior displacement of the
foveal retina, resulting in idiopathic macular hole.
7.06
Traction Maculopathy Caused
by Incomplete Posterior Vitreous
Detachment
Approximately of patients (average age 60 years)
who develop a symptomatic V\D will have evidence o f
vitreous hemorrhage or a peripheral retinal tear or both.
This affects twice as many women as men. hi all, 10-15 %
o f (hese patients Will develop a PVD in Lhe second eye,
usually within 1 years. Vitreous hemorrhage that Is usu­
ally caused by a demonstrable peripheral full- or parllal-
thickness retinal tear is lhe т о Ы frequent cause o f
transient loss o f vision in patients after an acute i’VL?
(figures 7.03 L> and 7.07A), hi most cases lhe macula is
unaffected by the ETL). Small hemorrhages around the
optic disc, along the major vascular arcades, and less fre­
quently in the macula may be the only sign of mtcro-
Lгаи т а to the retina caused by the FVD (bigure 7.07 A and
II). 1"1: When the PVD is impeded by abnormal vitreoreli-
nal adhesions In ihe macular area, tract ion and distortion
o f the macula may cause blurring o f vision, metamor-
phopsia, and occasionally a scotoma [bigures 7.05A^. G,
]. and |, and 7.07C-b and J-L). Ophthalmoscopic and
biomLctoscoplc examination reveals a parllat PVD and
tenting of the relina at the site o f the vitreoretinal adhe-
slon,25'30'"36-10 T b li site may be localized in the parafoveal
region rather than directly in the foveal area. If the onsel
o f symptoms is recenL. Lhe vitreoretinal adhesion may
separate in a mailer of days or weeks and visual function
may be restored to normal (bigure 7.07h, F, and L). 'Iliese
patienls, however, may subsequently develop evidence
of epiretinal membrane {figure 7.L17G). Jn a few cases an
epiretinal membrane may develop before PVD (a visible
Weiss ring) occurs [Hg]ure 7.0SA-C).
7.07 V itre o u s tra c tio n m a c u lo p a th y
A and B: This w om an experienced sudden blurring ol vision
associated W ith л pTeretinal hemorrhage caused by posterior
vitreous delachmenl and avulsion of a small capillary in lh e
viciniLyof the superolumpcual netjna vein jarrows);
C—G: A 41-year-old man noted sudden onset cl" blurred
vision and me(tarnorphci|Hia in the right eye да а result of
incomplete separation Ы the vitreous, which remained
allached to Ihe superior natal portion o f lhe macula (arrowy
1 ,i:n [1: i-fe I-i^Mrc r.UfiAi. I ne relin.il slri.ie r-adhted ouL-
ward Iran -, lhe т л е и Li. Visual acu ily was 2(V70. Angiography
revealed no definite abnormality, bight days later spontane­
ous separation of lbe vitnxjus was associated with a circu­
lar Lear in lb e |>оч’епот hyaluid in lb ?; foveal area :E ftnd Fl.
The condensation of lb e edges oP" the hole in the posterior
hyaloid indicated in the fundus painlin^, fF is no! visible in
E i'see Hgure 7.05И . Visual acuily returned to 20(2Ъ . The
relinal w rinkles noted in C w ere no longer visible. Eighteen
inonLhs laler h e developed Irie la m o rp h flp s ia caused b y c o n ­
tractio n o f an e p in e h n a l m e m b ra n e in the nasal h a lf o f Ih e
macula. N o le lbe lin e relinal folds radiating from the 1em р о ­
га] e d g e o f the m e m b ra n e (C .l
H : ftua macu lar yitreOus Iraclion causing relinal vesw l avul­
sion (arrow i and serous detachment of the гласи] л isee
Figure 7.05 Dl.
I: Vilreous Iraclion on lbe optic disc and juxlapapillnry relina
was responsible for liie misdiagnosis of p ap iIledema in this
patient (see Figure 7.05F:.
J-L: Blurred vision in a 02-year-old wrrfnan w ith m acular
edema rand detachment resulting’ tmff) prolonged vilreous
traction i see &iL;ure 7.05tl). Visual acu ily was 2(V200. Arrows
Indicate margin or lhe dttfathment. Angiography rescaled
evid en ce of cysLoid macular edema :K^. l'wenly-nine months
taler lbe vilreous separated and visual acuilv relurned lo
20/40 (L).
!H . f n :n L Ч ^ п к л п j n d I.L t n iit n ." : 3J- l (J£)-4. Д п н ч . L . i n iM c l I . i -. i I A s M i L 'i . h l i n n .
A l l r ijjh !!- r t ' M ; r w i l . '
 In some patients vitreorelinal adhesiott in the m acijjar
area is sufficiently dense lhaL prolonged traction causes
distortion, cystic edemar degeneration, and detach­
ment o f the тлей la. Ibis may be caused by a linear area
of attachment o f the posterior hyaloid Lo the retinal sur­
face (E ^uitt 7.07C), a single condensed strand o f vitreous
attached to Lhe paracentral retina, a cone-shaped mass o f
con denied vitreous wilh attachment Lo the entire foveal
timer surface (I'igures 7.05t and 7.07] and I.), and para­
central Lraclion at lhe mafor vascular arcades (Figure 7.07A
and J i). Vitreoschisis with spliLLing o f the posterior hya­
loid into two layers, and persistent broad attachment o f
the posterior layer lo the retina may be responsible for
this [Figure 7.081]. When lhe partEy detached vitreous
remains alt ached lo (he center of the macula, the retina
es tented anLeriorly, causing a localized tractional serous
retina] detachment lhaL is surroutided by radiating reti­
nal folds [Figures 7.03C, and 7.07| and U 7.0&C, E - H J:
Cystic changes are often evident centrally {I'igure 7. OS ГС).'11
Prolonged vitreous Lraction may be associated witfj angio­
graphic evidence o f retinal capillary permeability altera­
tions, and development of an epiretinal membrane in lhe
area of vitreoretinal adhesion. Spontaneous separation
o f the adhesion may eventually occur (Figure 7.07|-L).
Surgical separation of the vitreoreLinal attachment may be
required lo reattach the macula (I'igure 7.09J-F)I2" “*
Lysis of vitreoretinal adhesions may be accomplished in
some cases with Q-switcbed neodyjnium laser.'1*
Vilreous traction aL Lhe site o f a major retinal vessel may
cause not only a I rarlional retinal detachment that extends
into the macula but also avulsion o f the blood vessel
[Figures 7.05L* and 7.07И), vitreous hemorrhage, prolif­
erative retinopathy (I'igure 7.09]r and infrequently a full-
tbickness retinal hole’ 13-^
Vilreous traeLion on the optic nerve head and juxta-
papiltaiy relina may cause a fundus picture that simulates
papilledema, optic disc capillary angioma, astrocytoma, or
combined retinal pigment epithelium (IJPh) and retinal
hamartoma (Figures 7.05L and 7.071,- 7.09D--G, and see
Figure 7.26).
7 .0 S V it r e o t 'o v e a l t r a c t i o n c a u s in g m a c u l a r e d e m a a n d
m a c u la r d e t a c h m e n t .
A - D : A 7lj-year-old mule w ilh glaucoma and a visual
decline to 20/flQ ir his right eye showing a partial ring in Ihe
BrEifdrVEal vilreous (arrow) i A . Angiography revealed cystoid
m acular edarfia (В). O ptical o o h ^ t ic e fijntotfraphy iO C f :
revealed Irarticmal foveal detachment and cysts (C). A vrtrec-
lomy caused pfflrtipl resolution of Ihe cysls a nr I lhe detach­
ment.. w ilh vision recovering Lo 20/.Э-0.
t- H : lh is 1r--vv iг--;'! d ty p e 1 L^i.1 ! i wi l h p rio r p iu ir u in .il
p h o fo o o a g u la tio n for s e v e re p noliferatfve d ia b e tic re tin o p a th y
c o m p la in e d of floaters a n d ra p id loss o f v is io n in h it lefl e v e
o v e r 2 w e e k s . 1-1e had a lo v e a j d i'ta c h m e n l w ilh a prweLi-
n. 11 h e m o rrh a g e o v e rh a n g in g h is lo v e a w ilh in a v ilr e o u s tra c ­
tion b a n d (£j. l h e tra c tio n h a n d w a s c u n n e tte d Lu nn агед of
g lio sis a b o v e the s u p e ro te m p o ra l a r c a d e IF I. O CT s h o w s dis-
coiHim xiLy o l lh e o levaLod re lin a d u o Co -shadowing t'rom Ih e
p re fo v e a l b lo o d a n d m e m b ra n e (t^. A OCT seel io n ih ro u g h
Lhe e d g e o f Lhe v itre o u s b a n d s h o w s the lo ve a I d e ta c h m e n l
nnd the a tta c h m e n t of lhe b a n d Lo I fie re tin a ■
!1-31.
V it r e o s c b is r s c a u s in g m a c u l a r e d e m a .
I—K: This 56-year-old m ale shows evidence of splitting ol the
posterior uyiiloid iarrow) i.ll witii m acular LracLitjn caused by
the adherence of the posterior layer to Ihe reLina resulting in
diffuse macuEar edem a ф. PostvrtFectomy the m acular edema
resolved w ilh resLoralion of visfon lo 2 i\;2 5 iKi.
Ц U lira structure of the foveolar area lying belween Ihe smail
arrows shows a significant populalion ol '■ -■
1Li Nor cells (pale-
slaining cells indicated by I he- large a now ) in lhe и ml jo
region.
11., rrcmi I ki” .m uL .11. I
In some cases with unusual adherence of Lhe cenLer of
the fovea to the vitreous., a J’VLD thal begins in the extra-
inacular area may cause either a partial (lamellar) or futl-
thickness macular hole as it extends through the macular
area {Figures 7.051: and 7.09H, J-L). 'I'hts, however, is att
infrequent mechanism for causing a macular hole {see
discussion o f idiopathic macular hole in a subsequent
section].
Idiopathic Traction Maculopathy
Unassociated with Posterior Vitreous
Detachment
Jhere Is some evidence lo suggest lhal subtle changes may
occasionally occur in the vilreous body, causing it Iо con­
tract and to exert anterior traction on the retinal surface
posteriorly, without any biomicroscop ic evidence o f pos­
terior separation. or discrete vitreous bands allached lo the
inner relinal surface (Figure 7. L01L—I). This Iraclion may be
associated with cystoid macular edema and angiographic
evidence of retinal capillary Leakage in the in acu lar area or
serous delachmenL o f the sensory relina. (See discussion
ot" diabetic traction maculopathy, p. 544, and congeni­
tal pit of the optic nerve head, p. 12й0.1 Vascular leakage
or Inflammation wilh or without secondary vasajlal per­
meability alteration can result in vitreous соntradion
without posterior separation in conditions such as pari
planilis (Figure 7. ШЛ-D), retinal capillary hemangioma
(see Chapter 13)., Coats' disease, and others.
7 Vitreous traction maculopathy associated wilh
epiretinal membrane formation,
А—С : Л 26-year-old palienl initially was seen because of
blurred vision caused I?v viLrilis associaterl w ilh an active
focus o f lo«oplasmobis in the p«ri|з-hcinI fund lih. Three?
monLhs laler lhe vilreous cleaned and visual acuity returned
to 2Q/'2Q. O n e month later he devolopt'd crinkling of the
fnner refine I surface caused by an epi relina I membrane
farrows. A), Seven weeks later he was seen because of mela-
morphopsia. Tbr> vilreous alonj; wirh lhe Epiri'tinal mem­
brane had detached suppriorly and was adherenl lo ihe
center of the macula larrows, Bj. Visual acuity was 20/.10.
O ne week later Che vision had improved lo 20/20. The viL-
reous detach men I had exlended furl her inferiody. Six years
lalcr Lhe condensed b a ll of epi relina I mem brane (arrow, C}
and Ihe posterior hyaloid w ere Still al Inched lo lbe relina
inferonasally
D-G: This 65-year-old patienl developed blurred vision
associated w ilh a m acular pucker lhal appeared lo have
pulled free from its atlachment lo a branch relinal artery infe­
rior Lo lh e macula inferiftrly (arrow, D:-. Note Lhe suggestion
of a small vascular luft (arm m E J J Seven monihs later ihe
patienL returned with a semfopaque angiomatous prerelinal
lesion resembling an aslrocytom.i (Ef. Angiography revealed
a netTvascular frond w ilh in lhis lesion fF-:. O ve r Ihe nexl fi
months- I he lumor enlarged (C j. FblEowiOg phoLocoayulatioi:
Lhe palient developed subretinal freovascularliatFor,
H : M acular hole caused by vilreous Iraclion. Note irregular
inferior edge of holt1; where ihe flap has Lorn free. The oper­
culum i.irrnwi was alteched Lo lh e posterior hyaloid face.
In ilSflSj Lhis -FO-year-old man w ill: high myopia noLed
a paracenlral scoloma in the righl eye. O n e year later his
visual acuity was 20/25 bilaterally. Tbere was an incomplete
posterior vitreous delachmenl and adherence of [he Vitre-
o listo a focal area o f epireLinal membrane condtmsaLiun and
IracLional retinal delachmenl. Angiography demonstrated
evidence o f mild underlying depigmentation of the pigment
epithelium. O ver the subsequenl 4 years he developed a
focal area of geographic alrophy beneath the local area of
Lraclional roLina] detachmenL (II. The visual acuily was 20/30.
I and K: M acular dulat hmenl and hole caused b y vilreoLis
Iraclion. Note in Lhe stereoscopic view s ■J I the focal adher­
ence of lhe vilreous strand to Lhe edge o f the hole. Because
of persistence o f Ihe detachment a vLtrectomy was done and
the relina was reallat bed (K).
L: O ptical coherence tomography of a palienl with a full­
thickness macular hole with a complete posterior vitreous
detachm ent
Ihl, Imm I,i H£ll ''': Ll-t.i CfljjKtLiy uf Or Rubtrt ‘И.кТнмгтнл i
AtocitjfflraT^L’s 6-1-5
Traction Maculopathy Caused by
Spontaneous Contraction of the
Prefoveolaг Vitreous Cortex Unassociatec!
with a Posterior Vitreous Detachment
id io p a th ic Age-Related Macular H ole
Idiopathic age-related matttlar hole, referred to henceforth
in this section аз macular holt, affects predominantly
older patients, more often womeii) at a ratio of 2 or 3:1. '■
Jhey often discover blurred vision and metamorphopsia
when they cover the fellow normal eye.''1" " 11 Most patienls
report that bolh eyes were normal during their Iasi eye
examination I or 2 years previously. From the patho­
genetic and Lherapeulic standpoint, it is important lo dif­
ferentiate idiopathic age-related macular bole from the less
common causes of macular hole, such as trauma or macu­
lar traction resulting from incomplete posterior vitreous
separation, transvilreaL bands o f vitreous condensation,
or neighboring epiretinal membranes. An understand­
ing o f the structure o f the vilreous and aging changes in
its structure discussed previously in this chapter, and the
L il lr a s t n i c t u r e of the foveolar retina (Figure 7.0SL) are
important in considering the pathogenesis o f age-related
macular hole, which typically begins in eyes with an opti­
cally empty I iqueued premacular vitreous and no evidence
o f posterior vitreous sepa rati on,
It is Likely no other condition in ophthalmology hat
elicited as much debate and controversy about its patho­
genesis as macular hole, since the original description by
Gass. Et is important lo bear in mind lhal Gass described
Lbe mechanism much before OCIxvas available. W ilh the
advent o f O C T we began to view the interplay between
Lbe fovea and the vitreous, a concept Lhat Don Cass had
visualised by his keen observation wiLb a fundus contact
lens and interpretation ihe earliest observations with the
first-generation 0(71 were made by Alain Gaud tie, where
he introduced the terms "foveal cyst" and "anteroposterior
traction forces" at the vitreofoveal junction associated with
localized peri foveal vitreous detachment.1" Subsequent
reports have continued to use this as lhe basis of macular
hole formation.^ I’" Cass, xvho constantly reappraised the
Linders Landing of various diseases, in 19У9 wrote about
the forgotten "Muller cell cone" (Figure 7.1] К J and pos­
tulated dissolution o f the Muller cells in eyes destined lo
develop a macular hole. "A n inverted cone of Muller cells
occupying the inner half of the fovea centralis was firsl
shown by Yamada et al. hislopaLhologically in a 45-year-
old woman (Figure 7.081.). 1 Cass postulated breakdown
o f the compact arrangement o f the Muller cells and per­
haps their movement into the prefoveal vilreous cortex
in ilia Ling centripetal conlraclioti that pops lhe foveal
depression up (Figure 7.10J—L ). It is likely that the dis­
solution of the Muller cell cone weakens the fovea which
splits by Lhe contracting forces o f lhe overlying vilreous.
lhe concentric contraction of the prefoveal vitreous cortex
caLi explain the localized perifoveal vitreous detachment
7 .1[J Traction maculopathy unassociated with
posterior vitreous detachment
A-D: This- 21-year-old suliefed □ gradual decline In his right-
eye vision (o 20/200 over a year secondary to pars planLtis thal
responded to anLerfor suEbTenon Inamcjnalone injedion. The
dentdy gdherenl vitreous. in Che posterior pule ton traded,
resulting in retinal puckering and telangiectasia of IhE small
reLLnal vessels 4A and Hf. Optical coherence tomography
revealed tradion over iLw disc Lind posterior pole A tedious
,ind long vilTedomy resulled in removal of the densely adher-
r.ml v il их Ч, -. .and im[jrwvuniont in vision l i -'■> S o . К и to- the
residual papillomaculaT fold frcsn relinal redundancy second-
aiy So sLrelchiing hy IFm .1adhurenl vilreouK (D|l
E—1: Tiliн 15-year-old woman underwent a fritreclomy wilh
memEirane pee] after Lreinj’ sympLomalic lor more lhan 9
years. fro m id io p a lh ic i.sponlitneous) m a c u la r pucker. H er
viuua.1 acu ity w a s c o u n t lin g ers lh at im p ro v e d I о 2 0 /100.
1here w a s n o p o s te rio r h y a fu id sep a ra tio n ; lh e v ilr e o u s w .is
c o n tin u o u s w ith '.he m e m b ra n e that w a s m u lliL a y e re d an d
d e n s e ly a d h e re n t lo lh e re tin al s u rfa ce i G a n d H ). R e s id u a l
si n a tio n s w e r e ;и= п a I lh e re tm al p ig m e n t e p ith e liu m Level
fo I lo w i п ц v itre c to m y 11
seen on О С]' [E'igure 7. IK !) by foreshortening the vitre­
ous cones. Subsequent reports have alluded lo this con­
cept. 1 ihe role of the Muller celt cone changes in eyes
destined lo form a macular hole is further strengthened
by the observation of various other anatomic appearances
such as foveal cysts, foveal detachment, and diffuse foveal/
macutar thickening (Figures 7.07 and 7.CS), in eyes with
vitreomaeular traction alone, none of which leads lo a
macular hole. Figure 7 ILF also illuslrales that tangential,
ralher than anteroposterior, forces play a role Ln macular
hole formation; the operculum is Lying close to the fow-
ola rather than being drawn more anteriorly which should
have occurred if anteroposterior traction forces were
predominant.
Table 7.1 and the diagrams in Figures 7.1.0 (f—L) and
7.11 summarize the characteristic biomicroscopic features
and lhe presumed anatomic changes accompanying each
of th e stages о f deve Lopm en t o f a m acu Lar hole. 1
Stage 1-A: im p e n d in g Macular Ho/e
Although the earliest precipitating event responsible for
the progression o f changes leading Lo a macular hole has
not been identified, the author believes that proliferation
of Muller cells located in the center o f the normal foveola
(Figures 7.ft and 7.10J-I.) 1 and ihetr extension through
lhe LLM al Lhe umbo inlo the outer part o f lhe layer of
formed P V C is most Likely responsible for causing contrac­
tion, condensation, and partial loss of transparency o f the
outer part of vitreous cortex in lhe foveolar and perifoveo-
lar region. IJelinaL astrocytes and vitreocyles would seen]
lo be less likely candidates as cells responsible for induc­
ing contracture o f the P V C .75j l>Tangential contraction of
lhe ouler part o f the prefoveolar cortical vitreous causes
anterior displacement and serous detachment o f the fove­
olar retina (Figures 7.10К and 7.11ft). fttomicroscopicatly
a yellow spot appears centrally (Figures 7.1.2А лnJ 7.! ЗА).
Iliis. spot is caused by greater visibility of the retinal xan-
tbophyll, which is highly concentrated in thtL receptor
cells and nerve fiber layer in the foveolar region. It is more
apparent as lhe relink separates from the ftPE. 'Ihe patient,
particular^ if he or she has a macular hole in [he fellow
eye, may experience the abrupt onsel of melamorphopsia
Linassoci.aled with pholopsia or floaters. The visual acuity
may be almost normal. DistorLioti o f the Amsler grid is
usually present. EJLomicroscopically, there is no evidence o f
a I’VD but there is loss of the normal foveolar depression
and the foveal reflex. Eluorescein angiography often shows
a focal area of faint fluorescence centrally (I'igure 7.J3U).
Sfage 1-B: Im p en d in g Macular H ole
As the foveal retina elevates to the level o f lhe surround­
ing thick peri fovea I relina (figures 7.] 01. and 7.I1CJ, lhe
retinal receptor layer is put. on strelch and thinning of
the foveolar relina around the umbo causes a change in
the biomicroscopic appearance from a yellow spot lo a
small donut-shaped yellow ring lesion {Figures 7.t2t>and
7.14Л). Although a yellow spol occurs with foveal detach­
ment from other causes, e.g., idiopathic cenlral serous cho­
rioretinopathy. the change from a spol lo a ring is peculiar
to patients developing a macular hole. 1
Stage 1-B: QccuSt Mac и far H ole
Whereas die small central area o f iranslucence in the
center o f the \eltow spol may result from attenuation of
the foveolar retina, it is probable that lhe clearly defined
yellow ring that develops soon afterward is caused by
a break in the continuity o f the receplor cell layer at
the umbo. structurally the thinnest and weakest site in lhe
retina. This is followed by centrifugal movement of the
foveolar relinal receptor cells, their radialing nerve fibers,
lhe K luHer celts, and the xanlhophyll beneath lhe ILJv-t of
the retina and the со li traded PVti (I'igure 7.1lA(d and e)).
Initially the ]]_M of the foveolar relina and lhe thin layer
o f horizontally oriented Muller cell processes separating it
fro cn the retinal receptor cells may not be involved in lhe
central retinal break. Regardless, as long as the contracted
p refoveo Iar vilreous cortex bridges the hole, it may be'Visi­
ble biomicroscopically as a semilranslucent interface. Thus
Lhe change from a stage 1-Jt impending hole to a stage
1-b occult hole cannot be delected biomicroscopically.
Keadive proliferation of Muller cells and retinal astrocytes
occurring within the area of the receplor cell dehiscence
probably contributes lo lhe opacification of the tissue
bridging the defect and. in some cases, may cause ruffled
edges o f lhe relinal dehiscence surrounded by fine radial-
ing re Li nal fo Ids ( Figu re 7. ] 2C, and I ] ).
Fluorescein angiography in stage 1-ti lesions o f alt sizes
usually shows hyperfluorescence of variable intensity cen­
trally Although a high intensity o f fluorescence is more
suggestive thal a full-lhickness hole is present, angiogra­
phy is nol reliable in this regard.
7.10 Continued
H .: Diagrams illustrating presumed mechanism of
early macular hole developm ent
J: tA.lension ol" M uller cell? Ihrough Lhr? inlernal limiling
membrane of n?!ma inlo Lhe ouCer part of lhe layer of gelaLi-
nuuh vilreous corlex {чС) Га form a pTeloveukr vilrpoglial
membrane Jarrnwt-1. The tirftihiacijlar bursa (pmb) conlains
liquefied viLreoun. The doCled пШ пи Indicating lhe area of
highly conccmlrated relinal rarrthckihylj,
K: plage 1-A impending m acular hole. Condensation and
Langenlial contraction o! Lhe prpfaveolaif vlLreojilial mem­
brane tauKes; detachment cf" rhe fuveolar rcflinn. Separation
[il Lhe foveolar retina Ir-um [he pigment epi Ihelium causes
lhe xanlhophyll Lo be visible biomicnobcopically an a vellow
ypoL.
L: Milage 1-B impending m a c u la r hole. Furtfiec contraction of
Lhe pretoveolar vilreuylial membrane elevales rhe Foveolar
retina tu Ihe level <]{ the pdSrifmeal relina and fafclstt stretch­
ing and alien и al ion of lhe re lin a l receptor layer c e n L ra lly a n d
a change from a yellow sfiol I о a small, yellow, d cju gh nul-
ahaped finj^ biomicro!icopic^l3y.
Stage 2 H ole
Spontaneous VltrejJfoVeal separation may occur soon
after lhe central relinal dehiscence, and the contracted
I’V e becomes visible as a semitranslucent prehole opac­
ity or operculum-like structure Lying anterior to a small
foveolar hole (f igure 7.] 1Л (Q} . Initially the diameter of
ihis opacity is often taiger Lhan Lhal o f the foveal at hole.
In a few patienLs wilh early stage 1-Ji lesions, separation
of the EVC knay be accompanied by avulsion of part of
the foveolar retina, resulting in a true operculum forma­
tion. Hiomicroscopy, however cannot delermine the pres­
ence or absence of retinal tissue in (he prehole opacity. En
some patients the conltacLed E’VC, eiLher while il [emains
attached to and bridges the macular hole or after it sepa­
rates from lhe perifoveolar retina, may be transparent and
undetectable biomicroscopically. in such cases very small
stage 2 holes without a prehole opacity may be evident.
In most palienls, however, the contracted vitreous cor-
lex is semilransparenl and remains attached lo the inner
retinal surface surrounding the retinal hole as the foveolar
retina continues lo retracl cenlrifugally (Figure 7.11A(e)).
Hi оmicroscopically there is progressive enlargement of
lhe yellow ring, which may become serrated along its
inner margin that corresponds lo the edge o f lhe occull
round retinal hole (Figure 7.12FE-K). Eventually the finsl
bio microscopic evidence o f a dehiscence may occur in
lhe semi transparent vilreous cortex at the inner edge of lhe
yellow ring (E'igures 7.llA(gJ and 7 .12CJ). In the area
of the dehiscence, lhe serration of lhe yellow ring disap­
pears, presumably because o f relief of Iraclion on lhe
edge of the relinal hole, and lhe yellow pigmentation
fades, possibly as a result of diffusion o f xanlhophyll oul
of lhe relina in ihis area. Over a period o f days or weeks,
further en lavem ent of the macular hole and additional
contraction of the EVC cause a can opener-type 3605 tear
FJjjiflIfi&lJЩШ[,'Y ИОГ^ЛШ/. r/l
in the contracted l^/C, separating Ll from the less con­
densed outer vilreous cortex at the edge of the retina! hole
(E'igures 7.I I A(h) and J.12G-L)* lh e contracted prefoveal
vitreous cortex is visible bio microscopical Iу as an opercu­
lum-like Opacity (pseudo-operculum) suspended anterior
to the hole on the posterior surface of the layer of trans­
parent vitreous gel Lhat bridges the hole and lie^ along the
inner retinal surface in the macula, this prefoveolar opac­
ity oscillates slightly WiLh eye movements. Et is usually not
possible lo delect hiomicroscopically an interface caused
by lhe layer o f transparent vitreous cortical gel surround­
ing the pseudo-operculum.
Sta g e 3 H ole
Centrifugal ret radio n o f the foveolar retinal receptors
continues unlit the hole becomes fully developed and
its diameter in all bul a few cases reaches 400-600pm
(Figures 7.11 A{h}, 7 I2F and L, and 7.13C. G, 3. and K).
All stages of progressive enlargement of the hole are con­
sidered as stage 2 holes. Since the ultimate diameter o f lhe
hole is variable, for purposes of classification die author
suggests thal all holes les!i than 400pm in diameter be
considered slage 2 holes.
Stage 3 holes are associated with a mean visual acuity of
20/200 with a range from 20/40 to 5/200. Jhe sharply out­
lined 400-600-pm-diameter hole is typically surrounded
by a 1000-1500-|im-diameter gray rim of retinal detach­
m e n t . ■7i 'the palienL describes metamorphopsia on
the Amsler grid. A well-defined cenlral scotoma., however is
usually difficult lo demonstrate on the grid. Microperimelry
using the scanning laser ophthalmoscope demonstrates an
absolute scotoma corresponding with a macular hole, and
a relative scotoma corresponding with the rim of retinal
detachment surrounding lhe hole. With further refinement
o f the perimetric technique, it is probable lhal visual defects
Lhat extend beyond the area corresponding wilh the rim of
detachment will be detected. 9-63 N inety-ftve percent of
patients report a gap in a narrow slit beam of light (positive
slit-beam sign. Walzke sigjtJ when the slit of light is directed
Lhrough a fundus contact lens into the center of the macu­
lar hole. A 50-|im krypton or argon laser aiming spot placed
within a slage 3 or 4 hole w ill nol be seen in almost 100% of
patients (positive laser beam sign). thinning and depigmen-
talion of Lhe RE4-. develop within the area of the hole. A pig­
mented demarcation ring may occur (ligLire 7.15E'). Within
most holes. ihere are several yellow nodular opacities al the
level of lhe HFE (figures 7.12F:, h' and I, 7.15K, and 7. ! SC
and D], Jhese opacities change in number and distribution
from one examination to the other, ihe RE^L and choroid sur­
rounding the hole typically appear nonnal.. allhough some
palients in ay haw drusen. Several small inlranelinal cysts
may be evidenl near the margin of lhe hole. In 10-20% of
patients, fine crinkling of the inner retinal surface caused
hy an epiielinal membrane develops around Lhe hole, ihe
membrane occasionally may distort the contour of the hole
(Figure 7.15K). An operculum-like structure (contracted
7.11 L>iagra ms il Iu sIrat ing t he presirm ed a n atomy of
the stages of development o f an idiopathic macular
h o le L
A: Normal fovea. Layer o f vilreous- corLew (vc) lying on inter­
nal limiting гпетЕ>гапе of retina.
Slage 1-A imf rending hoSe. Early conlraclion (]1 о и кч pari
□i vitreous cortex w ilh iovuoiar deJachment.
SLage 1-B impending hoEe. d and e, Stage 1-E occuEL hole.
LJiriiiscunce of Lhe re lin k recepLor layer al lhe umbo w ilh
Cefitofugal redaction of the relinal receptors. ^tagc 2 hole
wiLh early нерлгаПоп o f corrLfensud pnefowolar vilreous оог-
Lex w ilh form alien ot pseutJo-opercuium that и larger Ihrin
lhe hole. g,. Slage 2 hole with tear in vilreous cortex at junc­
tion Gif Lhe prefuvuolar vitreous bttffejt and ed^t1 of m acular
hole, h, Stage 3 hole w ilh pseudo-operculum. \, 5la^e 4 hole
after posterior vilreous suparalion.
В: Y u Her cell co nt1 Mic.i. D raw ing of Lhe anatom y of lhe
foviea cerH-mlis showing M c r whose base :arrows) corre­
sponds w ilh Ihe internal limiting membrane, -and whose
ape* correspond;- with Ihe ouler limiLirg membrane cenlral !y
(arrowheadf. H enfe nerve fiber layer 1H> and foveal edge of
the ganglion cell layer (gj are shown. Drawing represents Lhe
author's interpretation ot a photomicrograph from Vaniada.
1Л/С) is suspended on the posterior surface o f Lhe hyaloid
membrane in front of the bole in 75-85% o f cases (Figures
7.I2HV Ei and Щ and 7.13C and E). In these cases there is no
evidence of a EVD except in die foveal area.
Sfagj? 4 H ole
After separation o f the vitreous from the entire macular
surface and optic discr irrespective o f its diameter- the hole
is designated slage 4 (Eigures 7. ]]A (i ) and 7.12C). Ihe
operculum-like opacity can often be found attached lo
lhe mobile posterior hyaloid membrane near the temporal
side of the Weiss ring.
Fluorescein angiography in patients wilh stages 2, 3, and
4 holes typically demonstrates prominent, early hyperfluo­
rescence caused primarily by lhe absence of xanLhophyll
in the area o f the hole hul is also caused by RPK thinning,
depigmentalion of the RPb, and slight loss of transparency
of the relina immediately surrounding the hole.''' ■' : ■in
palients wilh a long-standing hole, the central zone o f hypcr-
fluorescence may be surrounded by a rim o f faint fluores­
cence corresponding wilh Lhe rim of relinal detachment and
the underlying hjpopigjnented R[JH [Figure 7.131,). En a few
patients with a heavily pigmented choroid, the fluorescence
may be minimal or absent. Lhe yellow deposits within die
depth of lhe hole and the operculum overlying the macular
hole (Figure 7. J3J and I.) usually appear nonnuoiescent or
hypofluorescenl.
]f the anatomic interpretations summarized in I'igure
7.1 LA are corrcct, the implications include the follow­
ing: (L) most macular holes develop as the result of a cen­
tral relinal dehiscence at Lhe umbo, followed by centrifugal
 r_/3
V"j7n,4.vr> Тгасрпп Mn^itiL>'wthics

i 'i ir ii irt 1f m iV r t № ________ .................................................................................... Ilirni \jfilir in..............

Ift- ■
■" " '■**r.‘" ■
■
•“:■
■*■J---:: --■ ...........................
Ь State 1-A impending h:Je ; Slage 1-Б mcendhD bclE

/ *

(d ) StagE 1-Б Occuh halE \ b i Slage 1-S Gc-euIL hole

i;.
n.'ftfr*-.-! PHfiF.? - f l* . - 5 * Я ftfj
Ш ' 1
Stage t h:ie
® Slage Z folE

J
Staoe 3 hde £ j ';■ Slage i holE
displacement o f the idativety normal complement of reliniil
receptors; (2) ihis dehiscence occurs soon after the change
from a yellow spol (stage l -Л impending hole) to a y d low
ring lesion (stage l -И impending hole), but in mosL cases
El is n o t detectable wilh a thin slit beam as a defect in the
center of the ring because of lhe presence o f the sem[trans­
lucent condensed cortical vitreous bridging the hole (stage
1-1J occult hole); (3) most of the prehole opacities overlying
stage 2 and stage 3 holes are condensed prefoveal vitreous
cortex (p&eudo-opercLila)r not opercular and [4) following
successful vilreous surgery- which includes lamponade of Lhe
hole with an tntravttieal gas bubble, if done within 1 year of
commencement of bole fomtalion, the anaLomy of the cen­
tral retina and its visual function may be restored to nearly
normal levels in some patients os a result o f retinal reattach­
ment and centripetal repositioning of the retinal receptors. ]f
these concepts of the anatomic changes occurring in macular
hole development are correct histopathologic examination
o f the prehole opacities should determine thal most of ihem
contain no retinal receptor cells hut are composed o f vitre­
ous collagen, reactive Muller cell and astrocytic proliferation,
and jn some cases 1ЕЛ1 of the reLina. Although relinal oper-
cula have been described histopalhologicaily in two eyes, one
with postlrau malic and the other with an idiopathic macular
hole, it is uncertain whether the "opercula" contained retinal
receptor cells."'' Opercula have not been observed in most
idiopathic maailar holes studied histopalhologicaily.
Spontan eou s A b o rtio n o f Mac и far H ole
Form ation
in approximately SOftb of cases, patients with stage l -Л and
early stage 1-b lesions may experience rapid improvement
in visual symptoms because of spontaneous separation
o f the vitreous from the fovea without developing a full-
tbickness macular hole [E'igure 7.14). ^ [ nsuch cases,
the patient usually notices improvement in the symptoms
and biomicroscopy may show several different picturesr all
o f which are accompanied by return o f the foveal depres­
sion and a good visual prognosis.
Vitreofovea I Separation and Pseudo-operculum
Forma l ion
ihe foveal area returns to a normal appearance except for
the presence o f a semitranslucent. operculum-like sLructuie
or pseudo-operculum (condensed, contracted prefovea!
vilreous cortex) immediately in front of the fovea (Kigure
7.14A-C). When viewed obliquely with a thin slit beam,
the pseudo-operculum in a few patients will, cast a yellow
shadow on the pigment epithelium.*1Some patients wilh a
pseudo-operculum will notice a small scotoma when read­
ing and a few will describe il as having a yellow color.
Vitreofovea I Separation without Pseudo-operculum
Formation
After spontaneous vitreofoveal separation the fundus
returns lo a normal appearance and no pseudo-operculum
es evident.
7.11 Continued
C: The asympEomalic f-ellow -eye of a patient with a full-thick-
nuss c irc u la r hu]e s h o ^ n g early peri fovea I viLreouK detach-
menl; this eye subsequently developed я т л е н ha г hole.
D and E: Sl«j"u 2, А ЬВ-уид r-ol d wumflFi dropped her vbren
bo 2Q/S0- in her EefL eye. GpticaE coherence Lomogjaphy
■shcjwii lhe edgE 01 an operculum ax depicted in Л.
F: Stage 3 hole with an operculum lying just anterior to the
hoie.
(.j : Slsfje -f hole w ith Ihe operculum pul ltd aw ay Imm lhe
Imle due to suircequerrL posterior vilreoub detachment.
(j\ I r - > in (. i.L i- v hi, j d d p L e d f r n r n G j s s . u; I A m e r i i r . i n M c d i L '. n !
.-V is L K J M L ir jn . Л М n . ' h ' s г е м .т \ - 1ч.1. i
Vitreofovea] Separation and Lamellar Hole
Formation
Sepa ration of the vitreous from the fovea in these palients
is associated with a break in the continuity o f the tLM and
the bio microscopic appearance o f one or more sharply
defined reddish defects in (he inner relinal surface in the
foveolar area {E'igures 7.141U—b' and I and f, and 7.
Ait operculum is usually evident overlying the defect, lhe
defect may he minule and simulate lhal seen after sun
gazing or in patients with no recognisable cause fig u re
7.14J).' ' Larger lamellar holes often have a scalloped bor­
der (figure 7.14D). Unlike futl-thickness holes there is
no rim o f retina] deLachmenL. 'lhe visual acuity is usually
20/30 or better. fluorescein angiography shows minimal
or no fluorescence in the area o f the lamellar hole (figure
7.14Ei). The demonstration o f a focus of bright fluores­
cence wiLhin the area of the lamellar hole suggests the
possible presence of a ful E-thickness hole without a rim of
detachment (E'igure 7.13D-E7), 'Ibis type o f full-thickness
hole appears identical biomicroscopicallv ю a lamellar
hole, may be associated with visual acuity o f 20/30 or bet­
ter, and is likely to develop a rim of retinal detachment
and be associated wilh visual loss at a later date, lhe visual
prognosis for patients with a lamellar hole is excel lent.
Incomplete Separation of the Contracted
Pretoveolar Vitreous Cortex
A portion or all o f the contracted EVCJ may remain as a
smalj stellate opacity on the surface of the center of the
foveolar relina and be associated with fine stellate retinal
folds simulating X -1inked foveomacular schisis [figure
7.14K and L).fi4
il is important lo use a fundus contact lens to look for
signs of vitreofovea] separation not only in the symptom­
atic eye but also in the fellow eye of any patient wijh evi­
dence o f a macular hole in one eye. Spectral domain OCE'
is very useful in detecting Lhe relation of the posterior hya­
loid to the fovea, l^llow eyes wilh evidence of vitreofovea!
separation probably have less than a 5 % chance o f devel­
oping a macular hole.'" '"■'лли Some patients who have
reportedly developed a hole after demonstration of a IV U
probably had small occult holes thLit developed at the Lime 7.12 Stages of development of idiopathic macular
of Others probably had residua! vitreous cortex on holt\
the inner relin лt surface cent ml ly after separation o f the A and B: Progress ion of sJ-age I-A iтропе I i r>g amLUlat hole
vitreous from the optic disc and paracentral macular area. with yiellow spot (arrow, A J to stage 3 hole w ith prehole
opacity lalrcAy, E L
Natural Course C: Stage 4 “ii."it liLit hole With posLeOtw vitreous detach mcnt.
D -F: Progression stage 1-B yellow ring lesion I.Dj, to early
lhe Lime course from the development of symptoms and stage 2 hole Inole small eCtentrlc round hole and underlying
stage 1 impending macular hale to a fully developed stage yellow ileck al the 10 о гЫос:к edge of Che yellow ring, El,, lo
3 or 4 hole varies but in т о ы patients is within 6 months. slage .1 bole I Pi. Hrehole opacily P ^ e ly visible overlyihg Lhe
inferoCompora! Ьогккч of hole.
In some palients the course may be complete within a
G - J : Progressive enlargement o f can opener-type slage 2
matter o f weeks, and in others hole formation may not
hole farrows) that began at the 2:30 to 3:30 o'clo ck margin
have progressed beyond stage 1 till several years later, '['he of the yello w ring (<Jj. I^iee Figure 7.1 1G .) W h en last exam ­
visual acuity usually stabilizes after the first 6-12 months ined lhe holt1 extended from 1:30 Lo й o'clock tJ). N o le I he
at a mean level af 2 0/ 20C I. "' A few patients with stage serrated зплег edge t)f liie yellow плд in H and [.
3 and 4 holes may maintain excellent visual function o f К and L: This eocentrio can-opener tear extended 11 clock
20/40 to 20/50 for years. houre from 4:30 lo 8:30.

Spontaneous reatlaehmenl o f the retina surroutiding I I J - I - ;in d C - K , [r u m (.j.is s . V,- I 9 № , A m tlic a h M H id if .iJ А ч ы л -м ! i o n .

All r i^ iils r e s d V tf d .
the hole may occur (Kigures 7 .15G and 7.16) and the bio-
microscopic appearance may be identical with that o f a
lamellar macular hole. In some cases the hole may disap­
pear and recovery of vision may be excellent. Closure prognostic significance in the fellow eye is the presence or
o f a macular hole occurs occasionally as the result o f absence of a р у р ,5е |0иш* 'Hie reported risk for develop­
development of an epiretinaE membrane (Figure 7.16].' : ment of a hole in Lhe normal fellow eye has varied from
Approximately 2 5 % of patients with a macular hole 1 % lo 2 2 % .55j4j',fi3'65j6M,7i95' lDa" lClE ЧЪе probable risk is
have evidence of posterior Vitreous separation from the between 10% and 15%* lhe presence of a 14''D or vitreo-
optic disc and macula in the fellow eye. The macula of foveal separation probably reduces Lhe risk of developing
the asymptomatic eye is usually normal but it may show a hole to or less. Possible explanations for the occa­
evidence of previous spontaneous separation of the vitre­ sional patient with a PVD who develops a hole include:
ous that is limited to the fovea] area.1. In addition, other a tear in the posterior hyaloid at the lime of l^E}, leav­
minor changes may occur at the vitreoretinal interface, ing vitreous cortex attached lo the centra! macular area,
including epiretinal membrane formation., small irregular and a subclinical full-Lhickness microhole caused by
folds of the inner retinal surface, and absence o f the foveai traction during the F V D .HH In most patients the second
reflex, fluorescein angiography in the "asymptomatic eye" eye becomes involved within 2 yeareLM П ю ве with bilat­
is typically normal. 1Ъе value o f focal electroretinogra- eral involvement usually retain moderately useful central
phy in delecting predilection for hole development in vision, and mosL can read successfully with high-power
the fellow eye is uncertain.1' 0 The only finding o f definite spectacles.

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Pathology and Pathogenesis
Immunocytochemical labeling and electron microscopic
examination of vitreous removed at the time of surgery for
impending macu lar holes has demonstrated cortical vitre­
ous containing КРЪ and glial fells. Histopathologic
examination of a macular hole has failed lo demonstrate
any evidence of either retinal or choroidal vascular dis­
ease as a cause for the development of a macular hole
(E-'igure 7 .l5 ).K,'!i'-l0:,-ll-: lhe edges of the hole are typi­
cally rounded, some cystic spaces in the outer plexiforrn
and inner nuclear layers are often present, and there is
frequently cellular proliferation front the edges of the
hole on lo the neighboring inner retinal surface (figure
7.]5t;).IL'' Л cellular prehole opacity may occasionally be
observed (figure 7.15Л and Н]. It is not known whether or
nol retinal receptor cells are included.
Nodular proliferations of the RPEi overlying an eosino­
philic material probably account for the yellowish depos­
its noted biomicroscopically in the depth of Lhe macular
hole [E'igure 7.15C and E3). These appear to be identical in
structure lo the reactive, proliferative type ofdrusen noted
hislopiUhologically in eyes with long-standing relinal
delachmenl. [Proliferation of the RPE: is probably caused
by loss of the RPEi's contact with the outer segments of the
retinal photoreceptors as Well as its exposure lo the vilre-
ош .Ё5 '['here are two reports in which histopathologic
exam illation of the second eye in patienls with unilateral
macular hole found cystic spaces in the outer plexilbrm
Eayer in the paracentral macular area.^' 1:5 lhe fad lhat
fluorescein angiography in asymptomatic second eyes, as
well nis in thE affected eyes, shows no permeability altera­
tions suggests that these cysts probably are nol caused by
abnormal retinal vascular permeability, in spite of these
findings, which suggest that a slow process of cystic degen­
eration of the center of the fovea may predate the develop­
ment of a macular hole. Gass's observations suggesl that
macular hole development is not preceded by a gradual
change in either the appearance of the macula or visual
function. On the contrary, its formation begins abruplly,
although its full development usually occurs over a period
of 1-3 months. 'Iliere is no e vid e n ce to incriminate either
the underlying RFfe or the choroid in the pathogenesis of
macular hole formation.1,0, |и,|И As discussed previously
Lhe primary tissues involved in macular hole form alion
involve the vilreoretinal interface region in the foveolar
area. Election microscopic study of a series of prefoveolar
operculum-like structures collected at the lime of macular
7.13 Angiographic findings rn stages of macular hole
develop men I.
A—C: A slayc 1-A impending m acular hole developed in a
b2-year-dd Woman w ilh л 4^clary ЫнЮгу of meLamoi|ihup-
sia in lhe left ey*?. ih e had previously developed л m acular
hole m lhe riyhl eye isee I and |j. Visual acuily in lhe led
eye was 2CV40. Note central yellow lesion ГA.. There were
no cystic changes or evidence of a dehiscence in the ret­
ina. Angiography revealed slight fluorescence centrally IB;.
Twenty-six n^onlhs later 1C) a m acular hole with an opercu­
lum was presen] and lhe patient's visual acuily was 2W70.
D-F: W h a t appeared Id be an inner lamellar m acular hole
ID? showed local К 'р сП luoresconce i b r su^ostin^ the pres­
ence of an occult small sla^t! 2 hole. Ei^jhl monlhs later she
chim ed evid en ce or Ihe small si aye 2 hole with a rim o f reLr-
nal detachment.
(j and H: Slage 3 macular hole in a (>4-year-old woman wilh
a visual acuity of 20/100. Nole sharp margins of lhe hole,
surrounding halo caused by nutmill elevation and cystic
degeneration of Ihe relina, small yeMow deposits LhaL appear
lo lie on the surface of the retinal pigmenl epithelium, and
small prehole opacity lying just anterior (o the relina and
Hartly obscuring the underlying. vellow deposils from view.
The ret’nal vessels are wilh in normal Iimils. Fluorescein
an^io^aphy (H) revealed a circumscribed aired of hypejfluo-
rescence corresponding to Ihe size of Lhe retinal hole. This
fluorescence faded within i hour. The parafoveal capillary
bed was wilhin normal limits.
1 and |: 3 macular hole wilh prehole opacilv in a
62-year-old woman wilh a .'i-year hisLory of loss of vision
in !bt1- riyhl eye and a 4-day hislcrv of distifftEon of vision
In the lefl eye (see А-Cl. Vision in Ihe right eye was 20/200.
^rtgilwjraphy -|i revealed lirvfJerfluonescence corresponding to
the area of the hole and obstruction ot this fluorescence by
lhe piehole ofwacily.
К and L: A Ion$"-standing m acular hole and localised reLi-
nal detachment surrounded hy an epiretinal membrane.
Anyiogra phy showed lhal lhe w hile opacities within Lhe
hale wcto nonfluorescent (Lj, Nole rim of hyperftuoTescence
ar&Lind Lhe hole showing evidence of loss of pii’menl from
lhe rtitinnil pii’menl epi Ihelium in Ihe area of ]ong-slant;ing
relinal detachment surrounding Lhe hole.
hole suigery are needed to confirm theninalomic interpre­
tation of the biomicroscopic stages of hole development
suggested here by the author. !
'['he predilection foF hole development lo occur in
women has suggesled that ingestion of estrogenic com­
pounds may he of importance in the pathogenesis of mac­
ular hoib5**3 ^
Treatment
In s-Lir^ic-al separation of the IV C was suggested as a
possible treatment to prevent hale formation in patterns
with stage 1 impending macula holes.'"^ Uncontrolled
pilot studies of vilreous surgery for treatment of impend­
ing macular holes suggested that the surgery might be of
benefit.'1'■111 '■ -i2S ihe criteria used For an impending
hole by these authors., howeverr were not confined to those
of a stage I impending hole as defined by this author.>
l'urlhermorer there are many lesions lhal may simulate a
stage I hole and misdiagnosis of an impending hole is fre-
qu£fitS4 A randomi;ced, mulltcenler clinical trial to evalu­
ate the effectiveness of surgical peeling of lhe vitreous for
treatment of an impending macular hole in one eye in
patients wilh a stage 3 or 4 hole in the fellow eye was orga­
nized in l9 Sa The results of this study of 62 patients
showed that approximately 40^-а of eyes in both groups
developed a full-illickness hole. ЧЪе sludy was discontin­
ued before definite conclusions could be reached because
of a dramatic drop in patient recruitment coinciding with
enthusiastic reports concerning treatment of fu![-thickness
holes. W ith the following available information: ( I ) lhaL
40-6 of slage I holes spontaneously abort; [2] lhal
there in a high incidence of misdiagnosis of stage 1 holes;
and (3) the apparently favorable results of surgery for full-
Lhickness hole-s, It is probably pmdent lo observe patients
wilh a slage I Impending bote, particularly when the fel­
low eye is normal.
7.14 Aborted stages of development cf a macular
hole.
A-С: Th is wom an with a m at'u la г holy in the ft! Ikm- eye?
developed blurred vision and a slage l-G fesiqn in I he1
eye iA and top part ot" Cj. Several weeks later her symp­
toms disappeared and her Visual acuLLy and fundus returned
to л е гт п ! IE and bottom part of C l). Arruw in C l indi­
cates pseudo-operculum that was faintly visible biomicro-
scopically. This 70-year-old man noled melamorphopsia
H w hiie reading, of 3 weeks' duration. His visual acuity bad
decjeasctd lo 20/-Ю and careful biOpjUcroSCUpic examination
revealed vilreous tract ion. over the foveola. O ptical coher­
ence tomography confirmed foveolar elevation -second­
ary I о posterior hyaloid Iraclion ;arrow C2 above.'. H e was
observed and гЙ Ш пет b weeks laler with a W eiss rinj^ and
rcsl oral ion of visual acuity !o 20/20 iC2, tie low I.
D -F: This man w ilh a macular hole in his fellow eye devel­
oped meLamorphopsia and blurred vision in the lefl eye
caused by a Hta^e 1-A impending macular hole, hi is symp­
toms improved spontaneously and exam inal ion revealed a
Ia r;j; inner lamellar m.icuktr hole and prehole upacity iDf.
Note the sharply defined scalloped ed^es and absence of a
::m o f detachment. Angiography showed only faint ftuoies-
cence 1Ej. F indicates the probable anatomy o f this lesion.
His Visual acuity in Ihis eye has remained 20/25+ for 5
years.
 Kelly and Wendel in 1991,J ' Claser and colleagues
lj j I9^ 2 ,'"!' E’oltner and ’Lbrnambe in 1992,"'' and oth-
ers,<li' L:3D' 154 [n uncontrolled pilot studies,. reported suc­
cessful closure of Jiiaculлг holes and Visual improvement
using pars plana vitrectomy, intraocular gas, and ]-2
weeks of face-down positioning (E'igure 7 l&J. Glaser's
group used a tissue growth factor, TGF-p> to stimulate pro­
liferation of glial cells lo seal the hole. So me surgeons have
used the patient's serum hi lieu Of TGf-(Ji^i5 ilie visual
results obtained by all of these investigators were similar
in (hose eyes wiLh successful real Lachment of the retina.
Approximately 70% obtained improvement of Lwo lines
of" visual acuily or belter, and 20-40% regained 20/40 or
belter These same authors, who originally obtained only
approximately a 50% rcaltachment rale, have reported al
recent meetings successful, reallachment. in 90-95% of
cases and return of acuily to 20/40 or belter in approxi­
mately 50% of cases (b'igure 7.11fA-H). Keoperalion of
eyes with failed macular hole surgery may result in visual
improvement." 36i111
Since first conceptualized in 191 J9, removal of the ИМ
at the time of Lbe vitrectomy has vastly improved the rale
of hole cloture and decreased the need for repeat surgery.
Various methods to stain or delineate the transparent ILM
have been employed using indocyanine green [ECG], try­
pan blue, and triamcinolone. 'Ibxicitv with use of ICC
appears Lo be variable and related to the longer duration
of the surgery and the higher intensity of the illuminat­
ing light. SuFgical complications have included retinal
tears with and without retinal detachmenl. retinal vascular
occlusion; light lo r d ly pigment epitheliopalhy; cataract;
acLiLe permanent loss of temporal visual field, probably
caused by damage lo ihe nasal part oi" the optic disc dur­
ing Huid-gas exchange: and reopening of the macular
ho|e.'27.'29,!.ч.ив-'.и д clinical trial random­
izing patienls wilh full-thickness holes to surgery or to
observation is under way, and over ] 50 palients have been
randomized.1"
hollowing successful reattachment of the re<ina afler
surgery foF a macular bole, the macula may return to a
nearly normal appearance, the hyperfluorescence corre­
sponding with the hole preoperatively oflen disappears..
7.14 Continued
I t - 1 : This w o m a n n o Lt*d b lu rre d v is io n a n d m ttta m o rp h o p -
nia in lh e rig h t t?yt aji^b ci^ted w ith a sMgc- I -11 lesion ( G ) .
i b t ; im p r o v e d HponLn r>™ us ly a n d h e r 1. isual a c u ily im p ro v e d
la 2 Q '!3 0 . N o l e Ihe р л iг o f pa race n tral гп п ег la m e lfe r h o le s
(anow, Ih
J: N o L e lh e sm all in n e r la m e ] 1дг b oJe l^ n q w ) associate d
w ith 2 0 /2 0 visual a c u ity in this m a n w ith a stage Э Ею1е a n d
10 /2 0 0 vis u a l a c u ily in bis fa llo w e y e .
К a n d L: R a d ia tin g retina fo ld s associated w ilh stellate c o n ­
tracted p r e lo v e o lar v itre o u s c o rte x associate d w ilh 2 0 /3 0
vis u a l a c u ity in a w o m a n w h o p ro b a b Ey s p o n ta n e o u s ly
a b o rLe d a n im p e n d in g m a c u la r h o le .
and a cenlral scotoma may no longer be demonstra­
ble. 56,10 A few patients may regain 20/20 visual acuity.''4,
These surgical results were difficult to explain on Lhe basis
of the initial anatomic interpretation of the biomicro­
scopic stages of hole development.'1' 'Ihe p re bole opacity
seen in 75-ti0% of patienls was originally thought to rep­
resent an operculum containing the foveolar retina; this
operculum was thought to be derived from a circumferen­
tial tear occurring in the periphery of a stage 1-B lesion,
and significant improvement of vision even with reattach-
menL of the retina around the hole was thought unlikely.
Evidence now strongly suggests that nearly all macular
holes begin as an occult central foveolar dehiscence at lhe
umbo and [hat hole development is lhe result of centrifu­
gal sliding and retraction of the receptors away from lhe
center of the hole analogous to lhe opening of a lens dia­
phragm. U is understandable that surgical reattachment of
the retina around llie hole, xvhen accompanied by reac­
tive glial cell proliferation and contraction, may result in
"closure of the lens diaphragm" and return of (he foveal
retina lo its near-normal anatomic position and function
in some patients (figures 7.] a and 7.19). lhe disappear­
ance of the focal hyperfluorescence corresponding with
lhe iioler and of the absolute central scotomas lhal occur
in some patients after successful macular hole surgery, is
further evidence in support of the concept of centripetal
movement of lhe paracenlral retinal receptors and the
xanlbophyll.':'
 VTfju'uirs Tbicfmn Miati^ltrpaihlcs Gfa 3

O
'■M)'1
 The crileriл. for recommending surgery for a гиаси1лг
holt’ hate evolved o\rer lhe past 20 years. At lhe start most
patients undergoing surgery had symptoms for a year or
[esjir visual acuity of 20/70 or worse, and a large stage 2
or stage 3 or A macular hole. Lhe results of a randomized
study and olher reports broadened to include early stage
2 holes and holes of longer duration. Although the likeli­
hood for progression to a stage 2 hole is probably directly
related Lo the diameter of the stage l-B yellow ring and
Lhe level of visual acuily loss, there is no reliable informa­
tion or method at this time to determine which stage 1-fl
lesions will progress lo hole formation. л
The patient considering surgery ("or j macular hole
in one eye and having normal function in lhe fellow eye
should be aware of the following: ( I ) chances of develop­
ing a hole in the fellow eye are Ю—1!>% and probably less
than in the presence of vitreofoveal separation; and
(2) treatment usually involves two operations, Including
cataract surgery. N l-|:K'
l.aser treaLment lo the edge of macular holes has had
minimal success in improving visual function. l' 'lhe
treatment has no rationale as far as preventing further reti­
nal detachment in patients with senile macuiar holes is
concerned since the detachment involves only the cenlral
macular .irea and is unlikely to cause extensive detach­
ment in these patients with relatively emmetropic eyes.'"
Ihere is less chance for visual improvement following sur­
gical treatment of macular holes associated with other dis­
eases, such as diabetic retinopathy, Behcet's disease, or for
Itolcs caused by trauma.11'
7.1 j H rsto p a th o lo g y of a n id io p a t h ic s e n ile m actiEar
h o !f\
А' Cross pholo^raph showing rtim al “bperctilujiljr :.мггл№.
SusperMed in front (if Lhe holt.
B: PtiD b m icltig ijp h of retinal "opufculum " shown in A
demanstralcs ^li.il cells I jliI no defm ile Й£ЙЙепсв of feLi-
nal phokneLeptor [oils. This may be lhe lulled-up nudu3e
□f oontjatted prefav^oJaf libro^linl mem Ымпе and nut an
operculum.
C: H islopa Iholu^y of full-lhkkness rnacul® ht>Je with nodu­
lar pnolifuraLicjnii at the nelinal pigment tpitheliurn (RPE] in
Lhe? base Of lhe hnie (arrows*.
D : Higb-pHi'Wer view o f сЬдп^е in [he К PE shown in A
iarrows'!. \ti(e llial the anderlyinj’ choroid is w ithin normal
limits.
E: Hiyh-power view ol" the edf;e ol" Ihe? hole shown in C.
Note lh e extension uf relinal yiial L e lli (arrOWl on Lo Lhe
anterior surface ef lhe netin^.
F: Lon^-sl-andin^ mncuhtr hole with demarcation tirtjj
l.arraws'l composed ol proliferated R PE cells. Cbi2 l|b!T. yrade
1 idiopaLhic juxtafuyeotar relinal telangiectasia.
С : MactHaE hole with renltachrnenl of ils Efdges.
H : Inner lanwllar т а с ш а г hole.
IA J h d H . Гг<зп> f r a h g lu t i J.I " J n d H.. Iruan CIuvlt cjI a t..1 ■
 .д а *

® •R'■
 Macular or paramacular holes do not cause rhegmato-
genous retinal detachment unless they are associated with
a posterior staphyloma and high myopia,lW or with vitre­
ous bands causing traction on the surface of the posterior
relina. In such cases the detachmenl infrequently extends
beyond the equator. Treatment of such holes requires
either one or a combination of permanent or temporary
scleral buckling techniques; for example, the К Ioil! clip;
vitrectomy; intravitreal injection of air or gas; and cryo­
therapy, diathermy, or pbotocoagulaUon.11115l' 1'
Macular holes may develop in several clinical settings.,
some of which are unusual, e.g... Best's disease,l56,]!i7 adult
vitelliform foveomacular dystrophy.1 high myopia with
posterior staphyloma,' posterior microphthalmos,1 ''
congenital arteriovenous aneurysm,"" hypertensive reti­
nopathy/1,1,1 and following commencement of topical
pilocarpine therapy,163 _l:i pneumatic retinореху,l!" and
Nd-YAC posterior capsulotomy.l6S Macular holes occur­
ring in association with rbegmatogenous retinal detach­
ment caused hy peripheral retinal tears, trauma. myopia,
contraction of an epiretinnil membrane. and solar retino­
pathy are discussed elsewhere in this text.
7Ah Natural course ol macular hole,
A: Diagrafiti so w in g natural course of macular hole.
Stage 3 b o le , .M ost m a c u la r h a le s re m a in at 4 0 0 —6 0 0 (ц п
in d ia m d e r vviLh a m e a n vis u a l a c u ity ot 2 0 /2 0 0 .
Stage1 4 hole.. A p o s te rio r v ilre o u s d e La c h m e n l o c c u rs in
stm ie Ivoles. A n epi relin a I m e m b r a n e Ia rro w i o fte n b e e ttm e S
a m a r e n l c lin ic a lly a ro u n d b o th slage 3 a n d stage 4 h o le s.
T h e m e a n vis u a l hi-c:LiiIv is 2 0 /2 0 0 .
S p o nlnin eous re a lta c h m c n l o f Ihw re tin a . Thin o c c a s io n a lly
o c c u rs a n d lhe- vin u a l a c u ity m a y im p ro v e re m a rk a b ly - th e s e
hales are indislinguinhabit? b to m fc tiH p ttip ic s N y Iro m in n e r
La m e lla r h o te s (see В a n d C ) . A n g io g ra p h y , h o w e v e r , ty p ic a lly
s h o w s h y p o rflu o re s c e n c u in lh e fo rm e r a n d n o t the latter.
D is a p p e a ra n c e o f the h o le . T h e ed g e s o f the re a tta c h e d
relina m i i y llallen a n d m s o m e cases, not s h o w n o n the d ia ­
gram . llie y m a y b e d ra w n la g e th e r, p r n b a b Jy as the resu lt o f
glial p ro life ra tio n , in a w a y s im ila r Itji ibaL w h ic h o c c u rs in
p a tie n ts fo llo w in g v itre o u s surgery.
C lo s u re o f the h o le b y o v e r^ r o w lh o f nn cpi retina I m e m -
b ra n o . C< j t r t ip ± ] № o r O v e rg ro w th o f a n epi retina I m e m b r a n e
s u rro u n d in g [tie h o le m a y resull in its clo su re .
В a n d C: lh e rim o f d e la c h m e n t in Ihis slage 2 m a c u la r h o le
in E3 h^d s p o n ta n e o u s ly d is a p p e a re d ■<I) w h e n the pa lien I
re lu m e d fo r fo llo w -u p a lm o s t J years biler. Th e p a tie n t^
visual acuiLy w a s 2 0 ',2CM5.
 :

bags Ahffe

"D ьэрреггапое" of tele

Differential Diagnosis
Most palients referred lo the author wilh a diagnosis of
a slage 1-A impending hole have had a foveolar yellow
lesion caused by one of the following: solitary drusen..
small RPli detach me nl.. idiopathic central serous chorioret­
inopathy, foveolar detachment with epiretinal membrane.,
bilateral idiopathic juKLifoveolar retinal telangiectasis.. pat­
tern dystrophy, cystoid macular edema, and soEar macu-
lopathv (3:igure 7.17J.S;|
Lesions that may simulate a full-thickness macula hole
include an inner lamellar macular hole fMgure 7.14D),
a hole in an epiretinal membrane [Figures 7.17|-L and
see E-'igure 7.2ЭА). geographic atrophy of the RE1Ei ( Eigure
7.17Ci—1), choroidal neovascularization, a small focal
area of cenlral serous chorioretinopathy, cystoid macu­
lar edema with a large central cyst [Figure 7.17A-C),
focal retinal atrophy associated with bilateral juxtafoveal
retinal telangicclasis [E-'igure 7.171} and L) congenital
optic pit., and a soEitary macular cysl, a lesion that rarely
occurs.ILlfii 11'' 1 Е-'eatures of a hiII-thickness macular hole
that differentiate il from most simulating lesions are the
presence of a halo of relinal detachment surrounding the
hole, yellow deposits within lhe deplh of the hole, and
7 .17 Lesions simulating a macular hole,
A-С: Id io p a th ic c y s lo id m a c u fa r e d e m a IC M E ) w a s a s s o c i­
a te d w ilh a la f^ e cenlral cvsl ( A a n d C.i lhal w a s ttffetaken for
a m a c u la * h o le in- th i* m ;tn . y ^ ig iq flTH p h y re v e a le d I h e c o rn e d
d ia g n o s is iB>.
L>—F : B ila te ra l td ia p a lb ic ju K ta fo w e o la r telangiectasis w a s Lhe
ca u se o f the focal a tro p h y o f lh e relina ! D a n d F : lh a l w a s
in c o rre c tly d ia g n o s e d as a m a c u la r h o le , b e fo re lh e a n jjio -
t’ ram '.L) w a s o b ta in e d .
G - l : G e o g r a p h ic a tro p h y Ы lEie o u te r relina a n d relinal
p ig m e n t e p ith e liu m c a u s e d b y a ^ e -re la le d m a c u la r d e g e n ­
e ra tio n i C лп-rl Ej a n d focal h y p e rflu u re s c o n c e ■!H I w a s
re s p o n sib le fo r lh e i n t o n e d d ia g n o s is o f а пплсЫ аг Ew le in
Lhis e ld e rly p a tie n t.
a zone of hyperfluoiescence corresponding to the size of
the hole during the early stages of angiography. Lise of the
siil-beam lest (Walzke sign), S(J-|im-size aiming beam laser
perimetry, OCT. and lluorescein angiography are helpful
adjuncts lo contact lens examination in arriving at the cor­
rect diagnosis. Echography is capable of delecting PVD and
lhe presence of pseudo-opercula but appears lo he no hel­
ler than contact lens examination En this regard.-1'’
7 J7 Continued

J—L: This- p atie n t, wJk> hnid а гпасиЗаг h o le in lh e ri

h ad no c o m p la E n ts i r (h e left eye. V is u a l a c u it y w a s 20/20.
A c i r c u i t rim (if c o n d e n s e s v ilru o u s ly in g on lh e in n er reLi-
rj.al s u rfa c e c e n tr a lly I.Ej a n d m in im a l e v id e n c e o f c rin k lin g erf
lh e in n e r re lin k ] s u rfa c e suggested [h e p t f t e n c e o f a n o c c u ll
p e rifo v e o la r e p iie t in a l m e m b ra n e (L). T h e re w a s n o E v id e n c e
o l p o s te rio r VltrecJ^Js d e la c h m e n l. S h e so o n d e v e lo p e d я pos-
Lerior v itre o u s se p a ra tio n , m ild v is u a l b lu rrin g , a n d d e fin ite
e v id e n c e i f f л p e ric e n tra l e p lre tin a l m e m b ra n e i К :.

7LI 8 Dinigrj in о f s urg iсj ! rep л iг of пысиЗа r huleL

A: P te o p e ra tiv e a p p e a r a n c e of s la g e Э h o le . Air-ow in d ica te s

c o n tra c te d v ilre o u ii с о п е л '.pseudo-operc u k im : attach ed lo
the tayer o l v itre o u s gel ly in g b e tw e e n (h e liq u e fie d v itre o u s
(p ie m a c u la r b u r ia l a n d ih e re lin a l h o le .
B : I\ k Io p e ra tiv e a p p e a r a n c e after v ifre c to m y r su rg ic a l p e e l­
ing tif c o r tic a l v iffe o u s , ,ind in lra v itre a l gas fn je c lto n . W it h
the p aN en t in the fa c e - d o w n po^-iLiслл_. lh e b u b b le c o m p re ss e s
the ed g e s o f th e h o le a g a in s t the re tin al p ig m e n t e p ith e liu m .
С—E: E n la rg e d v ie w s to s h o w that p ro life ra tio n a n d co n trac-
lio n o f re lin a l g lia l c e lls c a u s e C e n trip e ta l m o v e m e n t cl" lh e
re lin a an d c lo s u re ol lh e hoJe.
F - 1: Th is Ь Е -y e a r-o ld w o m a n h a d л visual d e c lin e It) 2 O ,'3 0 -
o v e r 3 m o n th s , b h e h a d a stage 2 h a le w ith ап e c c e n tric
o p e rc u lu m stiEE a tta c h e d Lo the fo v e a l e d g e iF a n d G ) . H e r
vis io n im p ro v e d 1o 20 /3 0 fo llo w in g a v itr e c to m y vvilh inter-
naf lim itin g m e m b r a n e p eel le a d in g lo h o le c lo s u re J H j .
] a n d K : This ЬО-услг-oJd w o m a n s h o w e d c lo s u re of ho3e
an d Jjtiin ol" full fo veal th ic k n e s s o v e r b m o n th s fo llo w in g a
v ilr e c lo m y an d in tern™ I lim itin g m e m b ra n e p eel.

11 K, CDUYlыу йГ ]>г. Ргллса KtlClhl.h. I

 Gn^ m :b lv

^гегпк^бг t-ursa
 L.in i ted hbtcipatfmlogic information also supports ihis
mechanism of hole formation and closure (1'igure 7.1J‘t>—
G). tunata and coworker.s examined histopathologically
hoth eyes of a patient whose visual acuity improved from
20/400 to 20/30 in lhe left eye and from 20/400 Lo 20/40
in the right eye after surgery Гог a retinal hole.SJ1 I hey
found successful neattachmenL of the retina in both eyes.
Closure of the hole in the right eye was associated with
glial proliferation and probable centripetal inward draw­
ing of the retinal receptors (Figure 7.]9L>-h). In the left
eye retina] reattach men L was unassociated with gliosis.
Madreperla et al. reported their findings in another patient
whose preoperative visual acuity was 20/80 and postop­
erative acuity was 20/40.IH One month posloperaLively
Lhe patient died and histopathologic examination showed
closure of Lhe hole and close approximation of the reti­
nal receptors centrally by proliferating Muller cells (J-'igure
7 .1 9 G }.
7.19 5jrgical repair of macnEar hole.
A—С : Free pern live appearance o f stage 3 m acular hole (Af.
Vis uni .icuily, 20/30. Angiogram shawijjfl fljjfyheecertft con­
tra Ily. PosEuperali ve appearance (B). Visual acuity, 2Q/20. The
holt1w ; ls no longer I'videnC. Anyia^n'm i Q showed л rin^ of
pereislenl fluorescence.
U--!-: Preaperadve арроагагке ql а sla^e 3 hole :Dl. Visual
acuity was 20^200. Postoperative appearance (E). Visual
acuity was 20/40. Hi-sLopjatholo^ic exam inal ion o f lhe eye
uhliiintid At fltjulopsy shows ( losurc of hole Eiy proliferating
iji.il tfells ;arrow, F).
C : Histopalholo^y b[ л т л с и !л г hule following surgical
ret^lr sliows reappro\imation or lhe hole edjjes i.arrxjfws: by
M uller te ll proliferation.
IA —L \ c u u rlc iy y i;| dJr. t V i l i i . i r n I jm i-d iJ y : t - C I r u m l u n , i [ , i и I a l . 1" '
M A C U L A R D Y S F U N C T IO N C A U S E D
BY E P IR E T IN A L M E M B R A N E
C O N T R A C T IO N
After partial or complete PVDf a translucenL or semi-
translucent fibrocellular membrane may become appar­
ent ophLhilmoscopically and bio microscopically ол tbe
inner retinal surface in the macular area (I'igure 7.07C—Ci).
In approximately 25% of cases similar membra п н may
develop before deveJopment o!" A l3V£> (figure 7.09A-C).
Anomalous PV9 due lo spltiling of the cortical vitreous
lamellae may leave a residual cellular membrane over the
retinal surface that proliferates and contracts, resulting in
an epi ret Inal membrane. 22
lhe contraction or shrinkage of this epirelinal mem­
brane produces varying degrees o f distortion, intraretinal
edemar and degeneration of the underlying relina (Figures
7.20 and 7.2]}.*J-Lfi’-L™
Eipiretinal membranes may be classified according Lo
the severity of retinal distortion, associated biomicroscopic
changes, and associated ocular disorders.
Classification of Epiretinal Membranes
According to Severity of Retinal
Distortion
Grade 0: "C ello p h a n e M aculopathy”
In cellophane maculopalhy the membrane may be com­
pletely translucent and may be unassociated with any
distortion of the inner relinal surface, lhe only ophthal­
moscopic or biomicroscopic clue to its presence is а лсе1!о-
phane" tight refle* coming from the inner reLinal surface.
Grade 1: "C rin k le d C ellophane M a cu lopa thv"
Following contraction or shrinkage of the epiretinal
membrane, the underlying innej retinal surface may be
gathered into a series of small irregular folds 'Lhese altera­
tions produce an irregular iridescent light reflex, which
may be likened to that stemming from the surface of cel­
lophane that has been rolled into a ball and reopened
into a sheet containing many fine irregular crinkles on
its surface (figures 7.7G, 7.УЛ.. and 7.20Л. C, and F).
blomicroscopically. details of the underlying small reti­
nal vessels may be indistinct, bine. superficial radiat­
ing retinal folds extend outward from the margins of Lbe
con traded membrane and are often the most prominent
№ >-;-4bV:Г п Г г г У Л ? . 1даУiv-Li\-якцм.чi - V - : ** '
.н и п п и ш и ш ш т н ш .т о и ш н п и ш
7.20 Epiretinal membrane.
А: Diagram showing crinkled cellophane m ibtifcpalhy asso­
ciated w ilh Eire irregular wrinkles, o f the inner retinal layers.
Diagram showing macular tiucldfcr. Coarse relinal folds
□lien associaLed w ith relinal edema, cystic degeneration, and
localised delachment.
C-E: This patient developed rnelanifj-rpbopsi-a caused by a
small juxtafoveolar epiretinal membrane larrows). Note reti­
nal fa Ids radiating outward from lhe region ol the membrane.
Some of ihese pass through the m acula. Fundus painLing
of Ihe? same patient illusl rating Lhe relalianship ol the epireLi-
nal membrane (arrowh lo lhe underlying relina. Angiography
revealed mild torEuosily o f lhe relinal vessels in the region of
lhe membrane III: .
F: Semilranslucent epiretinal membrane causing distortion of
the macula of I his ЗЗ-уеаг-ок! palienl, who had no ol her e v i­
dence о I inlraocular disease. t.'unlraclion of lhe membrane
has pulled ihe param acular vessels Inward lhe horizontal
raphe.
С : I pi relina I membrane k'injj. in Ihe central area of the m ac­
ula in ibis Ы -year-u-ld girl, w h o had no oLher evidence of
ocular disease. Note retinal folds radiating oulward from the
macula.
Hi: F’rominenl epiretinal membrane in .i 40-year-old man
whose visual acuity was 20/20.
I- К : Epiretinal membrane causing macular pucker in a
72-yea r-old man who had no oLher evidence of intraocular
disease. Visual acuity was 201/400. Several small holes w ilh
an appearance similar to Swiss cheese were present in Lhe
relina superior to the m acula tarrowr ll. EJenealh these holes
was a small amount of SLibretinnil fluid. This palienl hiss
been oEiserved for ap p ro*iт а lely fl years with no l hanjje.
Angiography revealed marked tenlral displacemenl ol" the
param acular reLinal vessels Ф , early leakage of dye from
lhe retinal capillaries, and an irregular pa ILem of fluorescein
slaining in lhe relina IК and L). Tbe lypical cystoid palLern is
nol apparent Егесн-иье ef lhe marked dislorLion of the relinal
a rchi Leclu re.
sign indicating the presence of an epirelinal membrane
(figure 7.20C and L>). О С I' demonstrates fine superficial
wrinkles in the inner retina (I'igure 7.201.). 'ihe membrane
is often centered in the peri fovea I area but may occasion­
ally extend across the full width of Lbe macula. Lhe wrin­
kling may be sufficient lo produce tortuosity of the line
macular capillaries, if the area of membrane contraction
is sufficiently large. It produces tortuosily of the under­
lying paramacular vessels and displaces the surround­
ing retinal vessels toward the fovea (I'igure 7.20F}. Some
patients show multiple focal areas of preretinal mem­
brane contraction In the posterior pole. Cystoid macular
"J .....
in ' '■ | i IIIIMIIIIIlMllllllllllllMIIIIMII
 Л-Ьп'п/лг Djf/rJiinctifiTt Ёвизсф by EpititHnai M em b^n e Ccwr fitTLJTHJFT Ь{ 3

®
edema, retinaE hemorrhages, retinal exudates, and dis­
turbances of the R]°H are typically absent except in those
eases in which the vitreoretinal interface changes are either
secondary lo or incidental to other choroidal and retinal
diseases. Vitreous degenerative changes and a E]VD are
often present, inflammatory cells are usually not present.
When seen they surest that an underlying inflamma­
tory disease is present and lhal the inflammation is more
Eikely the cause o f rather than the result of, the epiretinal
membrane. Many patienls with grade 1 membranes have
normaE acuity and are asymptomatic. ОСГ may show mild
flattening of the foveal depression, without reLina! thicken­
ing or cysts I t-igure 7.2()[.). Some patients are seen because
of л mild visual disturbance in one eye. lhe patient is
often unable lo date the onset of" lhe visual complaint.
Acuily is typically reduced to a level no worse than 20/40.
Metamorphopsia is demonstrable in patients wilh reduced
acuity, 'ihe reduction in acuily caused by an epiretinal
membrane is primarily related to the distort ion produced
in the outer retinal layers [pholoreceptors) and nol to the
size or degree of translucency of the membrane. Visual
acuity may be unaffected in some patienls with prominent
centrally located membranes [Figure 7.20El). This taller
type of membrane probably is caused by cenlripelal slid­
ing of lhe contracting membrane along the ll.M
Grade 2: "M acufar P ucker"
Jhe epiretinal! membrane may be sufficiently dense lo
be visible as a distinct grayish membrane on the inner
retinal surface (figures 7.20b, ti-E, and 7.22A). ]l may
partly obscure the underlying relinal vessels, hi such cases
the degree of retinal distortion and crinkling is usually
marked, and gross puckering of lhe macula may be present
(Figures 7.201, 7.22A and C-t, and 7.23£]). Retinal edema,
small retinal hemorrhages, cotton-wool exudates, and
Localized serous delachmenl of the retina may accompany
prominent prerelinal vitreous membrane formation and
contraction. A Weiss ring is present in over 90% о Г cases.
Soon after the development of severe macular distortion,
angiography usually shows leakage of dye from the underly­
ing retinal vessels and evidence of relinal edema (E'Eguie 7.20|
and k). because of retinal distortion, lhe patient of d'ye stain­
ing is irregular and not typical of cystoid macular edema. In
a matter of weeks or months there is usually a reduction in
the amount of relinal edema and dye leakage. Visual acuily
is usually significantly affected. !t may he less than 20/200 if
the macula is severely puckered, in many instances patients
are unable to date die onset of iheir symptoms. En others,
ihey may suddenly experience cenlral photopsia and Loss of
central vision [I'igure 7.23C). Metamorphopsia is usually
demonstrable in these cases in which the entire thickness of
the relina is affecled by wrinkling.
IHpi relina I membranes responsible for puckering of
the retina may he eccentrically located in the paracentral
region, including the area of the optic disc, in xvhich case
Loss of macular function is primarily caused by traclionai
displacement as well as distortion of the foveal area (I'igure
7.2 E Sp on lane on s contra с tio n of a peri love of ar
epiretinal membrane causing a picture simulating a
macular hole.
Л -C: Mo It ■in epiretinal пнттпЬгапе simu lat ing a macular hoJe
in an asymptomatic 64-year-old woman w h o had 2 lY la visual
acuity and normal Amsler ^r:d, stalicr чэпе1 kinetic perimeUjt
findings in lhis eye. \oLe lhe fine.1 trinkiing Ы Ihe* inner reLi-
nal surface surrounding Ihe holt3 fn ал epiretinal membrane
and Lhe fine retinal folds radiating outward [rom the macular
атеа ;Ai. Angiography s-howod no abnojmaEiLy (B). tX JT Lind
diagram (C> sEwws fibrocellutar epi relina I membrane (arrow,
above* before conlraction, and alter Contraction i below I and
formaLion of a psuudomacular hole. The membrafte surrounds
bu! liues nol cover Ihe foveal a№a. H, Following sfionLane-
ous conlraclion of Lhe epiretinal membrane. Shortening of lhe
cells making up the epirelinal membrane produces an anle-
rior and centraE displacement of the inner retinal layers lo pro­
duce the- clinical picture of a pseudomacular Ewle. Nole lhal
there is minimal or no distortion of lhe ouLer retinal layer;; or
Lhe reLinal pif^nenl epiltieiium.
D - r ; Spontaneous parlial closure of" a hole in an epireLi-
nal membrane occurred in Lhis 69-year-old w o m m w ilh a
2-monlh hislory o f floaters in lhe rEghl eye. Visual acuiEy in
lEie ri^hl eye w a s 20/25 and in lhe lefl eye w h s 20/20. A poo­
ler ior vilreous deLachmenl and a tew cells in Lhe anLeriorand
poslerior vitreous in Ihe right eye were present. Note Jhe oval
hole surrounded by an epirdinal membrane :L3j. Fluorescein
ап^кз^гарЕп was ftormal. Fifteen monlhb later visual acuily in
the righl eye was 20/50. Furihter contracLion of LE>e epiielinal
membrane has narrowed the oval hole in the membrane to
a horiionlal slil lhal is now displaced lemporal to the cenler
11; '.he i i n .il.i 'I ■
. Lli,i^r..:ii I i jMr.Hes the- ■ )iilna< Lion ol
lhe epirelinal membrane and panial closure of lh e pseudo-
macula-r hole.
7.22С-Ь'.'\. Contraction of a juxtapapiElary epirelinal mem­
brane may occasionally be mistaken for papilledema or jux-
lapapillary combined RPE- and retinaE hamartoma.
Classification of Epiretinal Membranes
According to Associated Biomicroscopic
Findings
Foveolar H ole in Epi retina! M em brane Sim ulating
a Macular H ole (Pseudom acular H ole)
Spontaneous con tract Lon of an epiretinal membrane
that surrounds but does not cover the foveolar area
may produce a biomicroscopic appearance simulal-
Eng a full-thickness macular hole (ligures 7.17|-L„ 7.21,
and 7.24).J|1, 17j-171 Most of these membranes probably
develop before PVD and fail lo cover the foveolar area
because of the unusual degree of vilreoret Inal adherence
there. 'Ehe patient usually has no complaints, and visual
acuity ts normal or nearly normal. Kiomkroscopy reveals
crinkling of the inner relinal surface surrounding die hole
in Lhe epiretinal membrane and a punched-oul appear­
ance in the area of the hole. As the sill beam is moved
across the hole, there Is usually a light refle* that is evi­
dence of retinal tissue in the base of the hole, lhe foveal
r 1

I A
reflex is usually absent. Fluorescein angiography is gener­
ally normal [Figure 7.21 fi) but may show a very faint копе
of hyper fluorescence corresponding wilh Lhe pseudo­
hole. This zone of hyperfluorescence is lypically much
Lets prominent Lhan Lhe finely granular area of hyperfluo­
rescence seen with л fu I l-l hickness hole (I'igure 7 .1.IE-I,),
ihe presence of the semitransparent perifoveolar epireti­
nal membrane probably causes lhe foveolar area to appear
faintly byperfluorescenl by contrast lo the perifoveolar
area. Features of a full-lhickness macular hole, includ­
ing the halo of marginal detach men I, yellow deposits
within the hole and a translucent operculum in front of
some holes, are not seen in a pseudo macular hole. OCT
Will reveal retention of photoreceptors (Figure 7.22C),
unlike a full-thickness macular hole (I'igure 7. lit-’ and Ci).
lhe visual prognosis in these patients is good, in a few
patients additional contraction of an eccentrically located
perifovea! epirelinal membrane may distort lhe foveal area
(E'igure 7.2SD and h). En others the epiretinal membrane
may peel free from the inner relEnal surface [Figures 7.21]-
I.J. '] eardrop-shaped or slit like pseudomacular holes fre­
quently accompany a severe macular pucker Cion traction
of a pericentral epi retinal membrane thal remains firmly
adherent lo the inner retinal surface may cause an anterior
herniation of the foveolar retina through Lhe hole in the
membrane (L-'igure 7.21 G - 1) А 'ihis lesion may also
be mistaken fora full-thickness macular hole. Bonnet and
Heury noted lhe development of this foveolar prolapse in
Lhree eyes that developed recurrent epirelinal membrane
following surgical peeling о fan e^i retina I membrane.1 5
EpiF&tina} M em brane Formation A sso cia ted with
Full-Thickness M acular H ole
Occasionally vilreous contraction on Lhe retinal surface
around the foveal area may be sufficient lo mechanically
cause a ful 1-thickness bole in the macula (E-igure 7.24G-i)
or in the paracentral region (E'igure 7.20]J. Macular holes
produced by this mechanism are lypically oval or irregu­
lar in shape. They simulate closely a bole that involves
the epirelinal membrane alone (pseudo tnacu Iar hole).
Angiography in the former case, however, shows striking
hyperfluorescence соrresponding with the full-lhickness
bole (i'igure 7.24J|. it is usually impossible to determine
whether the macular hole occurred before the develop­
ment of an epi retinal membrane or developed as a com-
plicalion of the membrane. Mi Ed degrees of crinkled
cellophane retinopathy often accompany a full-lhickness
macular hole (Figure 7.13K).
Pigm entation o f Epiretinal M em branes
Hyperpigmentalion of an idiopathic epiretinaf membrane
may occur spontaneously in the absence of a reLinal hole
(Figure 7.22С and ID).1'" Pigmented epirelinal membranes
caused by a proliferation of $PE cells may occur, usually
in lhe extra macular region, in as many as 3 % of patients
following repair of rhegmalogenous retinal detachment.''
Sim ilar pigmented membranes may occur in the macula of
patients with peripheral retinal holes.1" J ' " I hey also
7r2E Continued
G - l: Anterior herniation o f lh e Foveolar retina FoElow-
injjj spontaneous contraction ol a periloveoEar epirelinal
memEirane iC and 31 was misihEerprete^ Lit а macular holt?.
Fallow ing surgical excision ol lhe membrane lhe visual acu ­
ity improved from 2 0 4 0 0 to 2CVo(J (H). Diagram il) illus­
trates the p ro fe s sio n of an epirelinal membrane laEiovei lo
relinal herniation |be Ia w after conlraclion ol lhe epirulinal
momE>rane.
I—L: This 57-year-old wom an complained ol mild blurring
of lhe rij^hl eye. Visual ncLiilv in lhe i i^hl eye was 20/25
and i . Vision ir: Ihe led eye was 20/20 and 1-1. Ntrte Ihe
pseudomacular hole .|) surrounded by an epirelinal mem-
Eirane. Fifteen monlhs iaLti-r Lhe patient was asymptomatic.
Visual acuity was 20/1 5. TEieepirelinal membrane had spon­
taneous I v pcelud from Lhe reUnal ниПасе :K.. Diagram it.
shows epirelinal membrane before (above) and after (arrow,
b e lo w peeling.
IA jnd tt. from U.isr1: and ti-l. frnni imiddy .irut G *u 1 ■ -J 1473,
Ann rir:.Ln Medical AiooCulitjri. All riL'Jilb rcHL-rvud
have been observed overlying pholocoagulalion scars.
Proliferation of pigmented as well as nonpigmenLed
RPE cells has been demonstrated histopalhologicaily in
epirelinal m e m b r a n e s . Jn some cases, pigmenla-
lion of epiretinal membranes may be caused, by lhe incor­
poration of macrophages containing either melanin or
hemosiderin.
C horoid al N eovascularization U nderlying
Epiretinal M em branes
Gass observed the development of choroidal neovascular­
ization in two patients several years after they developed
an idiopathic macular pucker. An unsuspected choroidal
neovascular membrane (CN VM j Was discovered by fluo­
rescein angiography benealh the pucker of another patient
referred for surgical peeling of the epiretinal membrane
(I'igure 7.22F and Fj. En these three patients ihere was no
evidence of any abnormality in the macula of the oppo­
site eye or of any other cause for the choroidal neovas­
cularization in the affected eye. Stereoscopic fluorescein
angiograms and OCF should be obtained Ш all patients
scheduled for surgical peeling of opacified epiretinal
membranes lo exclude the presence of occult choroidal
neovascula rizat ion.
Spontan eou s Separation o f an Epiretinal
M em brane
Occasionally the peripheral portions of the contracting
membrane detach from or slide along the retinal surface
and curl up into a roll or ridge al one edge of Lhe mem­
brane [Figures 7.2i J-U 7.22A, and 7.23G and ED).Ni9-
i л. i' l уj- ih • f^j3 process of sponLaneous peeling of a
preretina] membrane ofLen stops along the course of a
major retinal vessel, where the vitreoretinal adhesion
may be maximum. In some instances the membrane may
spontaneously detach from the enltre macular surface and
remain as an adherent localized mass in Lhe extramacular
Abtrt/Lir G-msni by E.pirctinal M&iibranc Coiibactum 67 7
region [Figures 7.£)9A-C and 7.23l>). Distortion of the
macula may disappear and visual function imp rows in
such instances. Spontaneous detachment of more periph­
erally located epirelinal membranes thal зге lhe cause of
fractional relinal detachment may also occur.'"'
Classification of Epiretinal Membranes
According to Associated Disorders
id io p a th ic Epiretinal M em branes
Crinkled cellophane maculopalhy and macular pucker mяу
occur in heallhv patients without evidence of other intra­
ocular membranes usually
occurin one eye of patients SO years of age or older. Both
sexes are affected equally. iUlateral loss of central vision from
severe pucker occun infrequently, lhe peripheral fundus
should be examined to rule out peripheral tears or retinal
vascular lesions. In 90% of the patients a I’VE) is present.' ' '
Macular dysfunction caused by an epiretinal membrane
is occasionally seen in asymptomatic children and young
adults in the absence of any history to explain their pres­
ence [Е-'igure 7.10G and 7.23E—E.). |:^л 1lj^ 'iltese mem­
branes in younger patients aie generally nonprogressive,
are frequently centered over major retinal vessels, and are
unassociated with a IVD . Occasionally they can be exten­
sive. multilayered, and strongly adherent lo the underlying
retina {I'igure 7.10K-H).
Retinal Vascular D iseases
Lpirelinal membrane formation occurs frequently in asso­
ciation with relinal vascular diseases causing intrareti­
nal exudation, such as diabetes, hypertension [see irigure
6.26H and I.), venous obstruction, telangiectasis, angio­
matosis (see figure 13.19}, and aphakic cysloid edema.
Macular distortion caused by the development of an
epiretinal membrane may occasionally occur early follow­
ing pholocoagulation of relinal vascular diseases, particu­
larly when the treatment is do tie in the paramacular area.
Retinal Tears an d Rhegm atogenous Retinal
D etachm ent
Crinkled cellophane maculopatby and macular pucker are
frequently encountered in patients either before or after
treatment for a peripheral retinal bole or a rliegmatog-
enous retinal detachment.-': ^ l}l Macular pucker is a major
cause of poor central vision after successful repair of a reti­
nal d e t a c h m e n t . It typically occurs B-16 weeks
following surgery. its development is probably determined
primarily by the events occurring at the time of vitreous
contraction and retinal hole formation rather than by
the type of treatment used. Nevertheless, various authors
have incriminated a variety of factors in its pathogenesis,
including preoperative findings of macular detachment,
vitreous hemorrhage, low visual acuity, rolled edges of
retinal holes, star folds, equatorial folds, cryotherapy, age
greater Lhan 30 years,-01 and multiple operations,-01'-11'1
as well as intraoperalive complications such as loss of
1,l'l P s e u d o m a c u la r h o le .
A: A ЬВ-уеа r-ol d asvm plom atic wom an hand 20/20 v isi cin and
a W eiss ring. The loveal center appears red against the jj^ay
contrast ol the epirelinal membrane that spares Lhe loveola,
giving il. Ihe appearance ol a psuudomat u3ar hole.
В and С: Similar ароеайпСе df a pseudomacular hole in
this f}5-year-ald wom an w h o also had optic disc drusen (Й):
GpLical coherence tomography shows preservation ol Lhe
foveal cones and early partial sepaTalion ol lhe epirelinal
membrane from lihe relinal surface (Cl.
Macular pucker.
D and t: M acular pucker with partial separation and rolled
edge o f epirelinal mumbrane Harrow, D). Note marked distort;
tion and displacement ol the retinal vessels toward the hori­
zontal raplH f: h I.
F and C: Delayed pigmental ion occurring ]n an idiopalhic
E!pi relina I membrane in a heallhy woman who was 57 years
□Id when seen initially in 1965 because of recent loss of
vision in 1he right eye. Her visual acuity was 2tV4ihl. She
had a nonpi^menled macular put kor ii'. ihe was observed
at yearly intervals until 1975, during which time her visual
acuity improved Jo 2fK'70 and lhe epirelinal membrane
became progressively pigmented iCr. There were no holes in
the relina.
H—J: This patient was referred to Ihr- Kascom ЕЫгпег Eye
fnsl ilu ltj for turcica i removal of an iditjpathic epirelinal mem­
brane in the rrghf eye (H and IK There was no biomicroscopic
evidence of ditimldaJ neovascularizalion. AnjJfbdRpby, how­
ever, unexpectedly revealed its presence l|J.
К and L: IdiopaLhic ju x ta p a p |l№ pucker and retinal neovas­
cularization in a 35-year-old man who noted metnmorpbop-
sia of 2 years' dura I ion. If is visual acuity was 20/25. Note
capillary dilation and leakage IK and L) w ithin tbe area of
the epi relina I membrane, w hose peripheral ed^es have con-
Lraclc’d toward Ihe; pa pi П о таем lar bundle.
vitreous and multiple attempts at sub retinal fluid drain-
age.Jut Коса I areas of epiretinal membrane formation in
the periphery of the fundus identical to lhat occurring
in the macula are responsible for the star-shaped retinal
folds that may accompany detachment. Macular pucker
and star-shaped folds represent mild forms of the more-
severe disorder of proliferative vstreoielinopathy (massive
vitreous proliferation), which is caused by cellular prolif­
eration, predominantly lhat of RPf cells and astrocytes, on
both the anterior and posterior surfaces of the retina.-06 j0.
Approximately 20% of patients who develop a macular
pucker after a scleral buckling procedure will experience
improvement in visual acuily.-':J 3>art of this improvement
is caused by relaxation or partial peeling of the epiretinal
membrane and pan is caused by partial resolution of the
intraretinal edema, which is more likelvj to be severe earlv^
after its development, particularly in aphakic patients.
fyitreo&s Inflam m atory D iseases
Any disease producing an inflammatory cellular infiltrate
in die vilreousT such as toxoplasmosis retinitis [figure
7.0УА-С], uveitis, trauma, intraocular tumor, or tapetoreti­
nal dystropIites, may be associated with development of
epirelinal inembrants in lhe macula.
Pathology and Pathogenesis
] Iistopa Lho logically, epireLinal membranes are composed
of a fib rocell ular sheel lhat varies in thickness Jrojii a sin­
gle hyer of collagen and interspersed cells (I'igure 7.25A)
to a thicker. mu] it layer of fibrocellular proliferation lhal
often bridges соагъе folds on the relinal surface ( figure
7.25ti). The latter is often associated with intraretinal
edema.1 precise morphologic
identification of the cells of origin of epiretinal mem­
branes by either electron or light microscopy is difficult
because of the ability of astrocytes, hyalocytes... librocyles,
macrophages,1' " and l?ETb cells to change into cells with
a simi lar appea ra nee and fu nclio n.1 1 t?e. iai.л L-Mf \-j
epiretinal membranes are composed of a variety of cell
types, including one or more of the following: myofibro­
blasts, RPE cells., fibrous astrocyles, fibrocytes, and mac­
rophages. 3:ew fragments of lhe footplates of Muller cells
are seen on the retinal side of the membrane.--"' Several,
and perhaps all, cell types have the capability of develop­
ing myofibroblaslic properties that are probably responsi­
ble for the contractile properties of epirelinal and vilreous
tnenibranesJ ] l '2 Epjretinal membranes can
be produced experimentally by a variety of techniques,
Lij^litding intravitreal injection -if Ы\?-ч1. carS'ii particles.,
fibroblasts, and ЙРЕ odis.^5,-13_Ji7
'lhe stimuli for epiretinal membrane formation are
poorly understood. A I’Y P appears to be one important
sti m uLus.3*$■1r'L-1 -241
Approximately 75% of epiretinal membranes are found
in eyes with a [ Т 1 > . ' ihese membranes are par­
ticularly prone to develop in eyes following Lransient
vitreomacular traclion soon afler separation of the vilre­
ous from the relina and wilh in weeks or several monLhs
after vitreous detachment and rhegmatogenous retinal
detach menl. J':u Two dilTerent mechanisms for epireti­
nal membrane formation and contraction after vitreous
delachmenl have been proposed. One mechanism (more
recendy, believed to he the less common) is lhe prolif­
eration and contraction of fibrous astrocytes that ejilend
from the relina and oplic nerve through either pre-existing
dehiscences in the ILM of the relina and oplic nerve head.,
or dehiscences caused by vitreous separation. 'L'bese dehis­
cences are most likely to occur on the oplic nerve head or
along the major retinaE vessels where lhe ILM is attenu­
ated. These fibrocellular membranes are composed of a
7.^3 Spontaneous separation and movement of
epiretinal membranes.
Л and B: NoLfc partial peeling anti superotemptэгаI displace­
ment or -ал epireLinal membrane (arrows) Lbal occurred over
5 yeare i п I his 44 -yea г-ol d rmi n.
С and D : Spontaneous detachment of the epi ml i гта I mem­
brane occurred in this Ь6-уеагч)Ы шйл who developed
acule lotF of vision, phnfrtpsja, and metamojphopsia caused
by m ac.ilar pucker I Cl 28 months Hitler ta la rad exLmcLion.
leven mo nibs after :i iн inilial cxaminaLJon, his vjsual acu ­
ity had returned Lo 20/30 and lhe condensed remnanl o f Ihe
membrane remained attached Lo Lbe relina in Lbe papillo-
macular bundle area (D).
E —H : This wom an with a hislory of a scEeraL buckle in lbe left
eye developed loss of cenlral vision caused by an epireLinal
membrane in lhe m acula (E). O n the buckle interiorly she
had an angiomatous prolileraliun of capillaries in lhe relina.
Angiography revealed fniid tortu($tity ol l.he retinal vasseW ii:
the area ol tbE pucker (I7} and staining of lbe peripheral neo-
vascular lesion. Several monih-s following laser I real menL ol
the neovascular legion fG'lj th e noled spontaneous improve­
ment in lhe vision and the epiretinai membrane in the lefl
macula bad peeled off the contra! macular area ;H;-.
1-L- This I I -year-old boy developed loss o f centtal vlsltm in
the right eye caused by a pucker (I). Angiography revealed
tortuosity and cenlral displacement ol the m acular relinal
vessels Islereo, J and Kf. Following surgical excisEor o f Lhe
membrane iL I lbe visual acuity improved from lo
20/25.
i l- L . . r l'L s y l i: D r 1 - Y lr .ik L H u ij j - . i m L - n . j
syncytium of cells i^'ith small, spindle-shaped nuclei and
scanly cytoplasm arranged in either a single or a multilay­
ered fashion a long lhe Inner retinal surface (Figure 7.25A).
Contraction and interaction of the cells rather than con­
traction of die extracellular component of lhe inembrane
are probably mosl important in causing relinal wrin-
kling.-1^ Electron microscopic studies of idiopathic epireti­
nal membranes have demonstrated that l?l3L cells and
fibrous astrocytes are the predominant celt type compos­
ing ihese membranes.-1"1Membranes in younger palienls.
ones in palienls with a history of recenl development of
symploms, and recurrent membranes are more likely lo
contain RE4i cells with myoblastic differentiation as well as
m y o f i b r o b l a s t s . O l h e r cell types that occasionally
predominate are fibrocytes and myofibroblasls.
A'lffcidfl?' ZhfpjitilcttpTt Ёвизсф by EpititHnai M em b^n e Ccwr fitTLJTHJFT 6H !
 Contraction of vilreous cortical remnants and prolifera­
tion and fibrous metaplasia of hyalocytes Eeft on the inner
retina] surface after an anomalous PVD constitute another
postulated mechanism for the development of epiretinal
membranes (I igure 7.02
This mechanism may be more comtncni in ihose
membranes (hat are thicker, Lnulli layered, and confined
Lo Lhe cenlral macular area lhan those that histologi­
cally nire hypocelJular.■" Anomalous PVD resulting in
vitreoschisis may he the precursor step in the formation
of epirelinal membrane. A split occurring in the more
anterior lamellae of lhe vitreous. cortex Eeaving behind
layers containing hyalocytes likely leads to epiretinal
jjp№nibraQE3‘l",SjT*6,"'l0r3*1 Kishi and Shimizu noted oval
defects in the detached posterior hyaloid membrane ante­
rior to the macula in most eyes seen with epiretinal mem-
branes.^5 They interpreted this js a tear in Lhe hyaloid
membrane that probably occurred before development
of epirelinal membranes in Lhe macula. ЧЪеу postulated
that lhe cortical vitreous remaining on lhe macular sur­
face acted as a scaffold for Lhe influx of cellular elements
responsible for the epiretinal membrane.
7.24 Pseudo macular holes and macuEar holes
associated with epiretinal membranes.
A -С: Н и к1 in partly del ached t!pireli п л I m enibrane (A and
C: HimubiLin^ ё macular hole and rim of relinal detacra&tenl
in an asymptomatic man w hose visual acuilv wjjh 20/25.
AngJilgfapby showed minigpfiH fluorescence centrally iLS;.
Diagram shows bole in parLly detached epi nul iu.il membrane
(arrows, tj.
D-F: H o le in p e r ilo v e o la r epiretinal membrane that is
d e ta c h e d a lo n g with the p o s te rio r hyaEuid Istereoscopac
v ie w ; [J a r d El и ппиla lin g л macular h o le . [V a g r a m iF- s h o w s
p res'Ei ntfi&d anatomy of the lesion.
G-L: Contraction o f epirelinal membrane associated w ilh
a full-fhickfiess rrta-cijlaf hole and relinal deladim enL. Note
ЫТ1-311 h o le -arrow, С on |une 12, l (J70. tpirelinal membrane
covers mosl of the inferdrtasal pan of Ihe: hole. By July 27^
1У70, Ihe тттл Ьгап е has conLracLed furlher лnrJ uncovered
a one-Lhiid disc diameter hole (H>. O n D ecem ber 4 r 1970^
lhe paLient noted further loss of uifitm caused by rhegmaLo-
f’enouh relinal delachmont (ij. Arrows indicaLe ouLer retinal
folds. N o le absence of Lhe Epiretinal membra гтг and hyper-
I kiorescerccu lh.il confirms л full-lhickness bole (arrow, J.i. N o
other hole was present. Ну February 9, 19-71r Lhe epirelinal
membrane had regrown across the hole .arrow; K'i. Ih e retr-
naf detachmenl persisted. PhoLocoagulalion was placed on
lhe m acular holtf. Ten monlhs later lhe epirelinal membrane
had reLracLud jnfeiiorJy, lhe macular hole was closed, and
lhe relinal dolachmenl had resolved L.i.
Prognosis
Patients with macular distortion caused by con tract ion of
an epirelinal membrane usually show little of no progres­
sion of distortion after their initial exami nation,]76rtfl3,] 69
A few patients, however experience a progressive loss of
visual fun cl ion over a period of months or years.*1 The
infrequency with which lhe distortion worsens suggests
that membrane contraction usually occurs rapidly and Is
self-limlllng. Angiographic evidence of retinal capillary
permeability is more likely Lo lie present soon after con­
traction of the epirelinal membrane has occurred, and In
eyes with membranes lhat are more likely to progress.-'1
Approximately 50% of patients maintain good visual acu­
ity, and in over SO^is lhe visual funcLion is either stable or
Improves, l-'ewer than 10% show a decline in visual acu­
ity Spontaneous peeling of the membrane occasionally
results In dramatic visual improvement (I'igures 7.0ЙЛ-С.
7.211-L, and 7.23С and I)) Spontaneous
separation of a preretinaE membrane in the macula is
particularly likely to occur following laser or cryotherapy
of a peripheral retinal angioma [t-'igure 13.19A-];J.J 'i:,",-':'
Angiographic evidence of leakage may be lhe result of
epiretln.il membrane formation, or nay he the precursor
of epirelinal membrane as in branch retinal vein occlusion
or relinal hemangioma.
Treatment
In the absence of any evidence of intravilreal Inflamnia-
tlonr there Is no reason lo believe that corticosteroid treat­
ment is beneficial in treating patients With intra ret Inal
7.2 j HistopalhoEogy of macuEar distortion caused by
epiretinal membranes.
A: h’fujCormLrograph of crinkled cellophane m aculupathy
shmvin^ fine w rin k iin j o f lbe innuf retinal surface res и I Li
Ггогл contraction o f ал ftpitfetin^J тегаЬгаще. A fine frbm-
cellular membrane farrow) lies on tbe surface o f tbe folded
internal limiting membrane.
B: ]>hi)LoniicTOf’raph hhuwjny macUtdf pucker, cybLoid mdt-
и!лг edema, and degeneration sdeunfliW to ccmlfaclicm of
an BtiirettnaJ membrane. The mem brant.1 is artilaclLLio’jf f y
detaCfi^p near Ihe 1а;где retina] folds Iarrow).
edema that may accompany a severe pucker. Surgical
peel nig of epiretinal membranes from the macular sur­
face has been successfully accomplished [f'lgure 7.2j5J-
£ уи *,2 5 1 -ж щ 5иг^]С:1| candidates are those patients
with moderate to severe visual loss, and a short duration
of macular puckering. Approximately 75% of palients
experience two lines of visual acuity Improvement after
surgery. Membrane peel with and without dye (ICG and
irypan blue) assistance seems to have similar ie*u Jti3*9“^ 1
Surgical complications include cataract (approximately
50-75% within 1 years), peripheral retinal tears, retinal
detachmentr posterior retinal tears, photic maculopathy
particularly wilh EGG dye assistance, anLerior ischemic
op tic neu ropathy, and endoph LbaIm i tis.J '"lJ 511_ J' J-J|,L - -74
fiegrowth of epiretinal tissue occurs in a smalE percentage
of cases. I'ailure to remove all layers of the epiretinal mem­
brane in multilayered vitreoschisls cases may contribute to
lhe recurrence.
Abtrt/Lir G-msni by Epirctinai M$fibmnc Coiib actum 68-5
Vitreopapiliarу Traction
Subretinal hemorrhage fl:igure 7.26), decreased visual acu­
ily, SWbllcn optic nerve head, peripapillary (raction detach­
ment, and intrapapillary anti epipapillary bednoTrbiges
are all signs that may be associated wilh vitreopapillary
tract i o n . C a r e f u l ЫотЕсгшсору with, a 7B-D or
a fundus contact lens often reveals an oval vilreous con­
densation iocaled eccentrically anterior to lbe oplic disc
with lhe absence o fa CNVM as lhe cause of the subretinal
hemorrhage. O CJ' is an invaluable tool in confirming lhe
traction exerted by the vitreous attached lo (he disc, but
detached elsewhere [I'igure 7.26C and I'). Vitreopapillary
tract ion in proliferative diabetic relinopalhy may con­
tribute to the visual loss in addition to other causes such
as poor macular perfusion, macu far edema, and vitreous
hemorrhage.t, J "J Surgical removal with pars plana vilrec-
tomy is indicated Гог decreased visual, acuity and/or a field
defecl.
R ET IN A L C H A N G E S A S S O C IA T E D
W IT H R H E G M A T O G E N O U S
R ET IN A L D E T A C H M E N T
Rhegmatogenous retinal delachmenl is one of Lhe mosl
important disorders of lhe vflreoretinal interface, and il
may cause or be associated wilh a variety of abnormalities
in the macular area. Approximately 30-40% of palients in
whom reLinal detachment includes the macula is'iIL regain
good visual acuily after successful ^attachment.'*1''" 14'
Most patients who fail lo regain good visual acuily will
show hiomicroscopic and fluorescein angiographic lesions
that account for lhe loss.1 ■
■|,'!' In some, however, usu­
ally those with macular detachment of 2 months' or lon­
ger duration, the macular area will show minimal changes,
and visual Loss is probably caused by failure of regenera­
tion and realignment of photo receptors. J ’jl
. .26 V itr e o p a p illa r y tra c tio n ,
A—F: An SO-уелг-old wom an w as follow ed for mild cystoid
macLiltir edema and viJroopapillary traction for 6 yeaJis with
a visual acuily of Z № 0 in bolh eyes lhal remained stable
(A . She developed iin asymptomatic juxliipjipillajy suhjeLr-
nal hemorrhage in the rrghL eye with no ch a rg e in her vision
(B). OpEical coherence tomography demonstrated attachment
ot" the vitreous to the disc surface bilaterally {Cl. Fluorescein
. 11 l.1i-:i-_:1!: - l w a s .ir i"1v . i : l - I J »:i:: I . She i i■
■ i\ ■■:
one ifijeciifin or bEWricizunniib for gfi erroneous dia^nwiK of
juM apapillan' choroidal i^ov^fcularizatiim with no change
in the hemorrhage. She had modera!u catanttlH and lhe
vision and vitredpapillary Iraclion ■:I-J remained unchanged
over b уедгк.
Epiretinal Membrane
lipiretinal membranes may be present before the devel­
opment of a retinal delachmenl but oflen become appar­
ent only during the postoperative course. PreoperaLively,
patienls with detachment and epiretinal membranes in the
macular area will usually show a stellate arrangement of
multiple, white, retinal folds (figure 7.27A and B}. These
are often accompanied by peripheral star folds, meridional
folds, and rolled edges of retinal tears, i’ostoperaLively,
epirelinal membranes are lhe most frequently recognized
abnormality in the macula.1''’"'^ Approximately 5 %
of palients undergoing scleral buckling procedures will
develop severe macular pucker lhal may or may not be
associaled wilh massive peri retinal proliferation and fail­
ure of standard scleral budding procedures. Vitrectomy
and surgical removal of ihese membranes are successful in
salvaging the sight in Some of these palienls.
Cystoid MacuJar Edema
Cystoid macular edema may be present either when lhe
patient is seen j nit Lai Iу w ilh a retinal detachment (Е-igure
7 .2 7 C ) or postoperatively. Et occurs most frequently,, but
not exclusively, in aphakic eyes. Cysloid macular edema
Lmd epiretinal membranes are the most frequent macu-
Ear findings in patients with poor acuity after buckling
procedures.
In most palients with rhegmalogenous retinal detach­
ment, fluorescein angiography shows no evidence of reli-
na[ Vascular permeability alterations. In long-standing
retinal detachment, however, angiography may demon­
strate evidence of capillary dilation, increased perme­
ability, and areas of capillary nonperfusion. In myopic
children wttH recent onset of detachment, angiography
may demonstrate large areas of diffuse Leakage of dye
[ E'igure 7 . 2 7 D - b ) . l U
Macular ard Paramacular Holes
Rhegmalogenous detachments caused by holes in the mac­
ula or paramacular region usually occur in highly myopic
patients with posterior staphylomata or in patients with
direct vitreous iraction on lhe posterior ret Ena.1 En
most cases these detachments are confined lo the posterior
half of the eye, and they infrequently extend out lo the ora
serrala. When lhe detach ment is con fined Lo Lhe macula
Ln patients with a posterior staphyloma and myopia, the
detachment may he caused by traction rather than a hole,
and spontaneous reattach ment may occur.Jlj: See discus­
sion in Chapter 3.
Approximately 0.5-1% of patients wilh rhegmalo­
genous retinal detach ment and a peripheral retinal hole
w ill also have a macular hole.191295 During the course of
surgery or immediately following surgery a macular hole
may develop in another ]-2 % of pat tents.JO-' rEuorescetn
angiography may he helpful in differentiating macular
holes from macular cysts, pseudo macular hole caused by
7.27 Macular changes in rhegmalogenous retinal
detachment,
Л: bad у sleilale pattern of retinal folds indicative of lhnL pres­
ence of epi retinal nbefnbranjfc.
B: Advanced stellate relinal folds in a patienl w ho developed
massive? peri relinal pnol i fera li о n.
C: Cycloid m acular edfitia lanrows).
D-F: А 17-year-old m yopic temaEe with recent onset of
rbe^jmatoyenous relinal detacbmcnl and multiple |эс-riphswaI
relinal tears. Nolc cloudiness c f subreLinal lluid and angic-
liraphk evidence (]f leaking retinal blood vessels.
G - l: Long-standing superior rhegmatogenous retinal detach­
ment and outer relinal cyst Harrow, H ) i n a 56-yea г-old man
who was asymptomalic until several days before admission,
when he noted loss o f cunlrai vrsion caused bv extension of
lhe deta chm en I jnlo the macula. Апц кэд™ phy showed early
hypeiiwotescenCe caused by aLtenuaLiun of the retinal pig­
ment epitbeEium and late staining caused by retinal capillary
l^jlkage in lh e iarea of longstanding detachment ■'I..
J: ^uEiretiniil librtnjs prphfeisUve bands and fenestralbd mem­
branes in a patient with long-standing relinal deLachmenl.
К and L: Subrelinal fibroLis strands i.arnow*' associated w ill:
,i Ifini’ -sMndinn nlVrin' rln-^i relinal del,n imenl
Ihat spontaneously real Iached. Sim ilar findings were present
in lhe opposite eye.
Iti-I, frurn Cj.l^b. ■ I
an epi retinal membrane (E'igure 7.21 Л and Щ, or parlial-
thickness macular holes (see figure 6.36).
Macular holes in non myopic eyes without evid en ce
of vitreous traction do nol require treat ment at the lime
of surgery for retinal detachment caused by periph­
eral retinal tears.™ A variety of techniques has been
employed in the repair of retinal detachments caused
by macular and paramacular holes in palients with
myopic staphylomata or posterior vilreous iraclion
(figure 7.0y|-L).-,4JJ,lS1 ■ ' 1 )
Pigment Epithelial Atrophy, Demarcation
Lines, and Subretinal Neovascularization
W ilh prolonged retinal detachment (usually beyond
□ period of Ь months )r Lhe RPb becomes partly depig-
menled within ihe area of detachment (figures 7.27U-3
and 7.2ЙК), and it ma\: proliferate along the junction of
detached and attached retina lo form a demarcation line
(f-'tgures 7.2SA, fl and K, and 7.28A-D). A series of these
[ine,s in ay occur as lhe detachment spreads over a period
of months or years. They may eventually extend into the
macular area (Figure 7.281.). Similar demarcation lines
may occur along (he posterior border of a chronic cho­
roidal detachment (E'igure 7.291'1 These ftPli changes are
more easily detected with fluorescein angiography [Kigums
7.271 and 7.18 K ).1"-■Д|У| Angiography is helpful in differ­
entiating a long-standing retinal detachment from relino-
schisis 'lhe latter condition is not associated wilh ftFE
changes unless il is associated with retinal detachment
from holes developing in Lhe outer and usually the inner
layer of ret inosch isis (i 'i gu re 7.30J .11:
3 have seen three patients wilh loss of central vision
caused by choroidal neovascularization at the edge of a
demarcation litie lying adjacent to lhe fovea! area (J-'igure
7.29 A-
Subretinal Fibrosis
A light gray fenestrated sheet or multiple opaque strands
may be present on the posterior surface of the detached
relina in approximately 3% of patients with a rbegmato-
genous detach menl (Figure 7 1 7 ] ) ^ " ® Subretinal
strands are frequently arranged in a relicular or other geo­
metric pattern, in some cases they may be separated from
Lbe posterior retinal surface. They are most often seen
in long-standing detach ment and are often associated
with demarcation lines, 'ihey resuk from fenestrations
7.2# Co nip Iic atio ns of to ng- stan di ng rhegm atogen ous
retinal detachment,
A-E: l'his yuun^ m yopic WQnjSj^n presented with bilateral
inferior relinal delat hments antj prominenl pigmented
dfemardatian lines fhal extended only to lhe peripheral mac-
i.j !i region in bolh c'yF':-.. A 11 11 I и.к k;i:iL| procedure
dfipne in Ihe left eye. lh e palienl elecled 1o have reinforce­
ment of Ihe dema real ion lines with laser plioLocoa£>ula(ion
rather than surgery in lh e ri^ht eye (A . She had no further
trouble for 10 yeary, when she developed evidence ol inLra-
relinal neovascularization and angioma Ions formation with in
the area o f relinal detachment, in the area indicated by the
a n o w in A. N o further LreaEment was done until 2 years laler
when the retinal tumor enlarjjed (E3) and caused symptom­
atic vitreous cells and mild cystoid macular edema (C, Ur.
FolltJVk'int; ar^on laser Inealment o f the angiomatous lesion
(B)r lhe lipid exudate disappeared :El and lhe vitreous ceils
and cys-lohd m acular edema improved.
F —J: Retinal angiomatous proliferation Ia nows, 1-K.j and
yellow inlrarelinal and sub relina I exudation developed in
a 24-year-old wom an with longstanding bilaleral inferior
rhe^miitojienouF. retinal delachm enb and demarcation lines
(G and НГ. The retina reattached after cryotherapy of the
angiomatous proliferation and relina Г holes. Note Ihe hyper­
fluorescence on Ihe detachment side of ihe dema real ion line
(arrow) in the iefL eye (K). 7*he demarcation line in Lhe left eye
was reinforced usin|^ ar^on laser.
K: Lar^e retinal fold running Ihrough Ihe macula in this
patient following a vitrectomy and scleral buckle repair of a
macula off retinal de1ac.fi merit. К ole lh e subretinal pcrfluor-
carbon bubbles Within Lhe fold larrowi.
IK , t - u u r l f s y aF Dr. b a k e r H u b b M n d .i
developing in large, thin fibrocellular sheeLs growing on
the back surface of the retina. En contrast Lo epirelinal
membranes, these usually do not affect Lhe incidence of
surgical success.506 Occasionally, however, one or more of
these strands may remain Laut after scleral buckling and
prevent complete reattach me nL of tbe macula.
Gravitation of Subretinal Pigment
Following Cryotherapy
ЁРЁ pigment liberated at (he lime of vigorous cryotherapy,
usually lo superolemporal holes in patients wilh relinal
detachments involving Lhe macula, may graviiale wtthiit
the subrelinal fluid lo lhe macular area. Ihis pigment
deposit may remain sialic or may become diminished Lo
some degree. IL is probably nol associated wilh any signifi­
cant morbidity in regard [o visual r e c o v e r y . ihis
granular, polymorphic deposition of pigment should be
dtslinguished from lhe pigmentation caused hy prolifera­
tion and fibrous metaplasia of the K Pt on the inner Fetinal
surface (Figure 7.25Ж and L).
Lesions Simulating Serous Detachments
of the RetinaE Pigment Epithelium
Early in the postoperative course following success­
ful repair of a retinal detachment, the physician may
nolice one or more Eesions wilh lhe biomicroscopic fea-
Lures of serous detachments of Lhe fePB in lhe macutar
region or elsewhere in the fundus (Figure 7.29Ci-1).1,11,1
Angiographically, however ihese lesions do nol show
staining Tvjth fluorescein, and they probably represent
focal areas of cloudy serous deLachmenl of lhe sensory rel­
ina. ihey vary in size from one-fourth to four disc diam­
eters. Several months or a year may be required before
resolution occurs. When Lhese lesions are large and soli-
Lary they are most likely to be misdiagnosed as serous
detachments of lhe ЙРЁ. When they are multiple they
may be mistaken for mullifocal areas of choroiditis.'■'
Similar lesions have been observed in experimental retinal
delachmenl.11
Retinal Neovascularization and
Angiomatous Proliferation Caused by
Chronic Retinal Detachment
long-standing rhegmalogenous relinal detach menl may
cause relinal vascular occlusion and focal proliferation of
prerelinal as well as intraretinal capillaries that may simu­
late a capillary hemangioma (figure 7.2ЙЛ-Г). 118 'Ihese
lesions may cause intraretinal and subrelinal exudation
7.l 1J M acu Iar com pIicat] on s associated with
long-s Ian ding relinal detach me nl.
A —C : Subretinal neovascularization (arrow, В j developed
w ilhin a pigmenLed derrtarcalion line in a patient who find
previous successful surgery for a long-standing relinal
delachm enl.
D Lind ErThis patienl тл'лн followed ior 3 years w ilh recuirejil
subfoveaf bleeding caused by subretinal neovascularization
occurring w ilh in a demarcation line ID :. Eight years afler Lhe
pholograph in L) she relumed w ilh evid en ce pf inLrarelinal
vascular pro I i fora Li on anti exudation K^npora] La lhe mnc-
ula '.tj occurring w ithin Liie а№а of inlraru1in,il m itral ion of
relii:al pigment epi Ihelium c-atysed by lo.ng-slanding rc-l i пл I
delachmenl.
F: Angiographic evidence erf demarcation lines yarrows:
caused by longstanding choroidal and retinal deLachment.
G : SharpEy circum scribed puddle c f subretinal fluid simulat­
ing Serous ret iта I pigmenl epithelium ih?I nfci detachment alter
sUpc^sful scleral b j.k lm g opemlion.
H —|: Sim ilar large puddle o f cloudy subretinal fluid (arrows,
H and l^ remained lor 3-4 weeks after a successful buckling
operation. Note the m ultiloculated appearance superiorly (l>.
Angiogmphv showed no evidence of K P t delachmenl l|j.
К and L: Pigmented ep irelink membranes causing m acular
pucker in two ]3tilicmIн following scleral Eiuckling procedures.
and occasionally vitreous hemorrhage. Similar prolif­
erative Vascular lesions as well as choroidal neovascular­
ization may occur al drainage sites made during scleral
buckling procedures. '|,J ',-tJ
Submacular Hemorrhage During
Surgery
Choroidal hemorrhage occurring at the time of drain­
age of the subrelinal fluid is the most common cause of
subretinal blood extending into the macular area. U may
occur occasionally, however, because of spontaneous rup­
ture of an occult CNVM in the macular or juMapapillary
area. Many patienls who have spread of subrelinal blood
into the macula from adjacent sources (e.g., CNV.Vls or
choroidal ruptures J regain good acuily afler clearing of the
blood. Eh is is less likely to occur, however, in patients with
rhegmalogenous relinal detachment.
Postscleral Buckte Macular Folds
Relinal folds extending into llie macular area may be lhe
cause of a poor visual result after a scleral buckling pro­
cedure. These may be either radial or curvilinear folds al
the posterior edge of a radial buckle lhal Was placed too
far posteriorly; radial folds extending from a drainage site
associated with retinal incarceration; or folds caused by
posterior slippage of the relina following the use of intra­
ocular gas in lhe repair of a large retinal lear (see figures
7.2ДК and 4.06C).
Retinal Crystals
Eyes with longstanding relinal detachment very occasion­
ally develop shiny fine crystals in the macula (figure 7.3! A
and il). 'ihe constituents of these crystals are not clearly
known; lhe possibility' of ihem being calcium oxalate crys­
tals is tnost believed. Whether they represent hemosiderin­
laden macrophages, eythrocyte breakdown produels,, or
pholorecepLor outer segments is still debaled. They do noL
aITecl vision, and often prom pi exploration for a localised
peripheral retinal detachment.,-1' 01
D EG E N E R A T IV E R E T IN O S C H IS IS
Degenerative retinoschisis is present in approximately
1-4% of healthy adull patients.1 tt most fre­
quently involves Lhe inferolemporal peripheral fundus and
is often bilateral Anatomically, the splitting of Lhe retina
usually occurs al lhe ouler plexiform layer but il may occur
more superficially (figure 7.31CJ. It. typically is seen clini­
cally as a sharply circumscribed, smooth, non mobile ele­
vation of the inner retina extending posteriorly from the
ora serrala (figure 7.31 D and ]■). It is nol associated with
changes in the RPH. which is in contact with the retinal
receptor layer in the area of the split reLina. The outer layer
7. ^0 Sen its schists detachment.
А and В: Thit Iw lr a n had peripheral reLi note iii sis with large
cuter retinal hales (arrowsf. There was no evidence c l eKten-
нion- of lhe sha3]ow retinal deLachnncnl surrounding lhe.1 holes
posLeriur Ic the Zone of ?chisiis.
C - J: Extension c f fluid from within the stliisi?. cavity lhrough
holes in lhe outer relin k layer (arrow, C'i into the s-ubrel i na I
sp.^ce in lhe m iicuia occurred in a fib-year-old man w h o
noted loss of vision in Lhe right eye. His visual acuity was
20^'hC). lie had a Jarjje bullous area or peripheral relino-
schisis temporally, associated with several large hotes (small
cirfown. [J and Ll in lhe Skiter reLinaJ laytir posteriorly. Л shal­
low serous relinal detachmenL extended from the edge of
Lhe ouler retinal holes; into lhe center of lhe m acula I large
arrow, D and F). Angiography repeated a la rye area of early
byperfluonescence indicative of relinal pigmonl epithelium
depigmontaLion wiLhin the атея& ot the cuter rc4innl holes
ia nows, C l and in а гопе c f lon^-slanding shallow rclinnl
deLnchmenl LhaL eslended from the posterior edge of the
holes in I о Lhe lemporal m a d jli (Hk Argon green iaser was
used I о 1ro.il Lhe edge of the o u Llt retina] halks and along Lhe
posterior edge of the schinis ll) m an effort to d c s e the neck
ol the delaehment. Because cf incom plete closure Ihe same
area was relneaLed never л I months later, and was successful
in reattaching lhe retina in Lhe m acular area (Jj. His acuity
reiurned Lo 2CV30.
IA лгкЕ ti-. C o u r t e s y cjI I Jr. ( , i m IH Л . MrcHik.i-l'ry; C .-J . I r u m Л г п Ы п г t:L i l . '■
is difficult to see without scleral depression, Retinoschisis
in mosL patients is asymptomatic and nonprogffesfftfi,329
Posterior extension of retinoschisis into Lhe macular area
occurs rarely and is most likely to develop in patients with
the reticular form of degenerative retinoschisis, which has
an extremely ill in inner retinal layer (figure 7.31 D and
E ) . * ^ n has been estimated that Lhe chance of retinal
detachment developing in a patient wilh retinoschisis is
0.04%.-” 5
K.ctinoFchi*i* 69ji
Sch 1sis Detachment
Jhere is some predilection for large areas of posterior
extension of schisis lo develop large outer-wall holes and
□ shallow retinal detachment lhat may slowly extend into
the macula (figures 7.30 and 7.52A-C, and
Before posterior extension of the retinal delachmenl
beyond the edge oftlM s.cKisi5. the detachment may be dif­
ficult lo delect. 'I'he presence of hypopigmentalion of the
ЁРЕ around the outer relinal holes or one or mure pig­
mented demarcation lines indicates relinal detachment
(I'igure 7-30Б and C). '['he relinal detachment extending
into the macula may be shallow and It anay be possible
to close the communication between the macular detach­
ment and the ouler-wall holes with one or more sessions
of moderately intense Iаь-er photocoagulallon across the
neck of the delachmenl along the posterior edge of the
schisis as well as along tbe edge of the outer-wall boles
(E'igures 7.30C-I and 7.32CI and 4 ).',kt In olher cases*
it may be necessary to employ vllreclomy and intravil-
real gas infection lo achieve resolution of the detach-
(ifrieriti32^ 30-3*3 Schisis detachment, when con fined lo
the peripheral fundus, rarely progresses and requires nu
Lreatment.*-'1 , lhe author be!ieves, however, that posterior
extension of schisis to near the macula, particularly when
associated wilh large outer-wall holes, const!Lutes a ihreaL
Lo central vision and should be delimited with several
rows of laser photocoagulation (figure 7.321 and K) w ith­
ou t wailing to demonstrate progression.
7.1 f Retinal crystals associated with retinal
detachment.
A and E: Pferiloveal distribution of shiny w hite crystals in this
paLienL with a ion g-s landing inFerior relinal delschm ent. His
visual acniLy wan 2(X2Q.
Degenerative retinoschisis.
C: F’holomicrcigraph sh o ein g ip lil at Ihe luvul Ы ihe tjerve
fiber layer (arrow) and «MunHivo cysLoid degeneration ol" Lhe
peripheral relina.
D : Stereoscopic photographs o f я large area of retinoschi-
sis lhat extends posteriorly into Lhe lumporal portion ol" Lhe
tnacula ;n this 52-year-old man, who also had геИпоьсЫяь
in Lhe other eye. Note there is no evidence o f retinal pigjnent
epithelium degeneration in ibeiirofl of Lhe relinoschiiis.
E—H : In Novem ber 1975, bilateral retinoschisis was noted
in ibis a Rymptuma Li с ЬВ-уч?а r-ol d wom an. In- lhe lefl eye iL
emended almobL Lo the macula <Ё). O n e year laler she I q s I
centгаI vision in the lefl eye because of m acular delachmenl
caused by a large posLerior cuter-wali tear at lhe posterior
edge of the retinoschisLs. A scleral buckle supplemented w ilh
pusLoper-alive phu1oc<Mgulation i}- anti C j was used in clos­
ing the lea г ; arrows i. 1'егт years later her visual acu ily was
2Q/30 (Hi.
9 and |: Spontaneous collapfe til drgenefalive relinoEchisis
rn this middle-aged wom an. Ih e ret inosch isEs Was present In
Fune 1 1; and had disappeared in September 1iJ79 (J.I.
A Jhd H-. Lourlef-v .>1 Dr. U.ivid Wtinbei^j; d£Urte=y f>l I Jr. Ho IjltLY
Или.:-
 Unlike palients with X-Jinked juvenile retinoschisis,
there Lb no evidence of any specific macular abnorm ally in
patients with degenerative Fetinoschisia. Detailed macular
function tests in these patients are com parable lo those in
unaffected patienls.'Jl'
Huorescein angiography shows no ahnormality in the
background choroidal fluorescence in Lhe area of retino-
scbisis (Figure 7.29B and C} as long as there is no hole or
detachment in Lhe outer retinal layer. En some cases there
may be evidence of retinal capillary dilalion. leakage, and
dropout in the inner retinal layers.
The pathogenesis of degenerative retinoschisLs is
unknown, bul chronic vitreous traction on the peripheral
Lcli:t,i lit,!-. :=
n predispos'd micituyMoid degeneration,
particularly on Lhe lemporal side, is probably impor-
LanL. Lhe scbisis begins W ith coalescence of the cysls of
IJlessig-lwanofT microcystoid degeneration resuEting i.n a
system of Lunnel-like spaces in the outer plexiform layer.
Subsequenrty a second independent system of spaces
develops at the level of Lhe in n e r nuclear layer. Al first
Lbe inner aLtd outer systems are separated by the junction
of the neurons wiLh the horizontal cells lhat He between
the inner and outer pleKtform layers (ligure 7. j 2A-F).
Gradually the supporting columns between Lhe cysls dis­
integrate, splitting Lhe remaining relinal elements into two
. 12 Retinoschisis.
A—F: А ЗЙ-year-old male w ilh recent decrease in vision
in [he left eye Lo- 20/100. Ttie right eye saw 20/20. A |ar£e
r4..'linr)S(.hi!iiii wan seen in Ihe inferolernptjfal region of Lhe
Il'Il eye extending to the foveal center, in addition I и flecks
of fundus fIHviividcuIrilliн in lhe? posterior pole in bolh eves
iA-C:. An ouier reLinaJ Ljreak. w ith adjaccmL subrelinal flLiid
was found at [he superior edjje of the scbisis (C, arrow J.
H p licii] Loh-erence ttKiiujjraphv lhrou|^h 1fie foveal cenftr
rind elsewhere revealed vertically onenled не hi sis cavities l l J
rind Ё). A settlo r through Lhe area of [lit; outer break dum»n-
sUalud subielinal fluid tieneaLh Ihe schisis caviLy ■:Fj. H e whs
treated w ilh bra. I and lopical a'cetaXalanj ide and Fefracted 1o
20/40 with a hyperopic согтес:!ion.
layers with sparse cellular connections in between them,
mostly made up of Muller cells. At this slage, the surface of
the relinoschisis shows pitting corresponding Lo the foot­
plates of" tbe Muller cells (I'igure 7.Д2Н). Eiventually when
the tissue pillars undergo complete necrosis, the layers
separate Completely.''11 The material LbaL fills the cavity is
composed of mucopolysaccharide and is believed to result
from (he breakdown of the tissue elements, 334
K.ctinoFchi*i* 699
 Spontaneous reattachment of the inner 1лует occasion­ 7.3^ Continued
ally occurs (figure 7.29H and I). No treatment is indi­
С and H: Laser applied lo -an outer relinal break ih пгт pye
cated unless a retinal detachment associated with inner w ilh exIпепле thinning of lhe H^hisis Livers.
and outer retinal holes develops or unless there is dem­ I—К : This 4Ch-year-okl hi jj.h myopt1 и№ found to have a Ia rye
onstrated progression of schisis (Kigures 7.311 to K) or a Hthiaii in Ih r inferolempoml quadram on гишИпе exam i­
schisis detachmetil with quter vrall holes into the macular nation 41 a r d J !■
_ Two уеагъ later the cavity had enlarged in
area. height and etetende^j posteriorly iK?. 'She underwent laser
demarcation of the relina pustLvior lo the schists in an
Most degenerative retinoschisis occur independently;
attempt lo prevent tufther ртоугсгиап.
however association with nanophthalmos, high myopia,
Ml.' ,in d I I.. tr ju r lc js y nf U r. 4-r.iix.o C e c t h i j .
and tilted discs has been reported."'1 ' ' ' Acquired retino-
schisis and retinal folds occur as a sequel to the retinopa­
thy in children suffering nonaccidental trauma.' ' '
lietinoschisES is most likely to be mistaken for a local­
ized rhegmatogenous retinal detachment or occasionally
the reverse. Jhe typical configuration of the elevated inner
retinal surface, absence of evidence of visible and angio­
graphic changes in the underlying RFEL and presence of
an absolute scotoma are features suggesting relinoschisis.
lhe presence of a demarcation line is strong evidence of
a rhegmatogenous detachment, which in the presence of
schisis may be difficult Lo identify. Angiographic evidence
of depigmentation of the ЯРЕ peripheral to the demarca­
tion line indicates present or past retinal detachment in
Lhat area.
K.ctinoFchi*i* /0!
AMYLOIDOSIS
Loss of vision caused by accumulation of atnyloid in
tbe vitreous may occur in primary familial amyloido­
sis wilh or without systemic Involvement and occa­
sionally in patients with neither systemIc nor familial
JnVtoL^ment-340-35*
The amyloid is probably produced tn the relinal ves­
sels and secreted inlo lhe vllreous. iiarly, it may produce
prominent perivascular sheathing and localized vllre-
ous veils.35-1 Later, as ihe vitreous becomes more opaci­
fied. ii has been described biomicroscopically as having a
cot ton-wot) I, glass-wool, or cobweb appearance [Figures
7.33 A and 7.34/V Б, and H). It may be misdiagnosed as
Inflammatory exudate or resolving retinal and vitreous
blood. Cotton-wool spots unassocialed with hypertension
occurred in one patient.'5'"*
Hlslo pathologically, amyloid may be demonstrated
within and surrounding retinal vessels as well as within
targe choroidal vessels and the choriocapillaris {Kigure
7 .3 3 £ ].f^ W
Vilreous deposits in amyloidosis occur primarily in
patients wilh dominantly inherited amyloidosis associated
with peripheral neuropathy, amyloid nephropaLby, and
cardiomyopathy [familial amyloidotic polyneuropathy)
(bigures 7.33Ё and С and 7.34А, Ё. and E).*41 150 Most of
these patienLs haw a mutant form of the protein trans­
thyretin associated wilh a mutation in the transthyretin
gene.,3Slj3!i',"3S6'35? 111 is mulatlon may be present in patients
wilh vitreous opacification and no family history of lhe
disorder.1ie Ketlnal neovascularization and vitreous hem­
orrhages occur In some patients associated with elevated
vascular endothelial growth factor k s e l s ^ * 1 3lH)
Talients with vitreous opacities should he checked for the
transthyretin mutation even when they have no definite
family history of amyloidosis. Additional means of diag­
nosis include biopsy of affected organs, including ihe eye,
kidney, or rectum. Liver transplantation is promising by
eliminating production of (he abnormal transthyretin in
Lbe liver. Ocular involvement has Increased or occurred
after liver transplantation in some patients secondary to
continued retinal production of translhyretin.!G| M’~
lam ilial oculolepiomeningeal amyloidosis (heredo-
oto-ophlbalmo-encephalopalhy) is characterized
hemiplegic migraine, periodic obtundation, psychosis,
seizures, carpal tunnel syndrome, inlracerebral hemor­
rhage, myelopathy, deafness, cerebellar alaxla. peripheral
neuropathy, visual loss associated with relinal and vitreous
infiltration with amyloid anti cataract, and systemic organ
7.33 P rim ary amyl oidosi s.
A —F : iiil-J a m p p h o to g ra p h o f Lhis 6 2 -y e a r-ol d m a n w h o
e ip e fie ftc e d p a in le ss loss- o f vis io n fo r several
y e a rs Ь е с лине o f a m y lo id d e p o s itio n larrow 'i in lh e v ilre -
дУ-S o f b o th eyes ГA.!-. H is past m e d ic a l h is to ry w a s p o s itiv e
for s evere p e rip h e ra l n e O ro p a m y a n d tbe c a rjia l Lu nnel s yn ­
d ro m e . K a l e lh e a tro p h y a t lb e s k in a n d m u s c le s o f Lhe
h a n d s a n d feet (B a n d C ) . H is fa m ily h is to ry w a s n egative'. A n
o p e n -s k y ie n s e c Lo m y Hind v itie c lo m y w e re d u n e . H is vis u a l
a c u ity u n p ro v e d fro m c a u n L jn y lingers at li fo o l p 0 c m :
Lo 2 0 /3 0 . N o te Lhe re m n a n ts Ы a m y lo id o n lh e o p lic dist
(ajTtWiV a n d o n Ihe relina l isiirfa-Le te m p o ra l 1o lb e m a c u la
I.arrow , b H e s u b s e q u e n tly d ie d o f a c o r o n a r y Ih ro m b o s is .
P h o to m ic ro g ra p h (£) s h o w in g a m y lo id d e p o s i t o c c lu d in g
m u c h of" tbe c h o r io c a p il laris a n d w ilh in th e w a ll o f lh e iarye
choroidal vessels (a'lroViT-'.
G a n d h : Th is 5 1 -y e a r -o ld w o m a n w ith d o m in a n L ly in h e rite d
o c u lo le p lo m o n in ^ e a l a m y lo id o s is h a d а 20-\чздг h is to ry o f
pro gressive p e rip h e ra l n e u r o p a th y c a rp a l Lunne! s y n d ro m e ,
h y p e rre fle x ia , d y s a rth ria , nysLa jjm usr a n d m e m o r y loss.
V isu a l a c u ily w a s 2 0 fl 5 b ila te ra lly . In Lhe p e r im a c u la r area
she h a d n u m e ro u s superficia l gESW.-white lesions lh a t sLained
a n g io g ra p h ic a lly I G a n d H i . O n e y e a r later she d e v e lo p e d
visual loss, v itre o u s opacificJffltior, a n d Lh ic k e n in ^ o f Lhe
Lo n g u e . V is u a l a c u ity im p ro v e d fro m 2 0 / 4 0 0 to 2 0 .4 0 in b o lb
eyes fo llo w in g v itre c to m y . T b e v itre o u s e x h ib ite d d ic b ro is m
a n d s ta p le d p o s iliv e ly for a m y lo id .
I—I Th e 2 S -y e a r-o ld -son of lb e pa lien L in CJ a n d H h a d a h is ­
to ry o f h e rm p le y ic m ig ra in e a i*d s^i^ures b b d in n in g in his
te e n a g e years-. H e d ie d at a y e 2 9 years fro m c o m p lic a tio n s
ol in lra c e re b ra l h e m o r rh a g e . I^sthologic e x a m in a tio n o f Lhe
e y e s re v e a le d b ire frin g e n t a m y lo id d e p o sils in Lhe b lo o d
vessnl w a ils a n d p e riva s c u la r sp a ce s or" lb e relina (a rro w s ,
I (tT o n y o re d s la in ' a n d J Ip o la r ize d fi^ h U ), e x te n s iv e a m y ­
loid d e p o s itio n in lh e le p lo m e n in jie s a n d the b lo o d vessel
w a lls w ill’ in the le p to m e iiin g e s : a r r o w *, К a n d L i.C o n ^ o re d
stain) f. O t h e r o rg a n In v o lv e m e n t in c lu d e d Lhe h e a rt, a lim e n ­
tary tra c t, skeletal m u s c le , a n d nerves.
MJ bind b. frumK.LHicr ljI .ii ' ; I-Lr frurn L.ilLi fl a.I 1 MJBfl.
A m e r lc a h M n d lc a l ЛИ гекь'гт.-^с1.
involvement (}:igure 7.33G-I.).' ' ' ' Ihe retinal lesions
resemble cotton-wool patches but histologically are amy­
loid infiltration of Lhe retina (Hgure 7.33С and I).
Crawford reported cotton-wooE exudates in a patient
with nonfamilial systemic amyloidosis and no evidence
by of syslemic hypertension. " 'v Histologically, these reti­
na! lesions were swollen, degenerated, necrotic axons in
lhe nerve fiber layer unassocialed with amyloid deposits
in either Lhe relina от the vitreous. Amyloid is known lo
deposit in and around the retinal and choroidal vessels,
sometimes causlnga severe chorioretinopathy.'''
 * , ft
О
 Vitrectomy is the only effectIve means of restoring
vision in patients wilh amyloidosis {Figures 7.33D and 1:
and 7.34C and f } ) 347-1^ 365 Removal of as much of the vit­
reous framework ль possible Is Indicated since recurrence
of the amyloid deposits may occur. "'11 I№ ihe material will
stain with Congo red and show typical yellow-green bi­
refringence wilh polarized light (iigure 7.34E-). I\in ret Inal
photocoagulalion is required for eyes wilh retinal neovas­
cularization and vitreous hemorrhages.
A S T E R O ID H Y A L O S IS
Asteroid hyalosis is a degenerative disease of the vitreous
of unknown цацйе.377-3^1 il Is characterized by the devel­
opment of white or yellow-white spherical or disc-shaped
bodies (asteroid bodies] composed of calcium soap within
the collagen framework of the vitreous (i'igure 7.351
and K). They develop initially in the vicinity of the reti­
nal blood vessels and may eventually he present in such
Eaige numbers throughout the vitreous thal visualiza­
tion of the ocular fundus is nol possible. In spile of this,
however, the patient's visual function is only minimally
affected. Fluorescein angiography may provide an excel­
lent view of the fundus when it is obscured ophthalmo-
scopicall.y (Figure 7.33! and h:). " Histopalhologicaily,
the asteroid bodies have a crystalline appearance and they
stain positively wilh fat and acid mucopolysaccharides
that are unaffected by prelreatment with hyalurouidase. iaj
J hough asteroid bodies have been extensively Investi­
gated, their origin, inode of formation, and composition
are incompletely elucidated. Ultrastructu rally they are
composed primarily of mullilantinar membranes typical
of complex acidic lipids, particularly phosphotlpidsr and
are associated with calcium phosphate со m pi exes lying in
a homogeneous background m atrix.^ 384 in addition lo
calcium and phosphorus, the most detectable elements.
7.34 Amyloidosis
A-f: A 42-veaj-old Korean mafc noted flo aM S and prtDgres-
sivu dim inulion of vision uvuf 2 yean;. Hi к viKU^ auuily was
counl finycvs in lhe riyhl iind .20/50 in the left еутез. Dense vit­
reous (.i- p H c itn e o v a s c u la r k a lia n of the? relina, and relinal
Btemarrhflges went1 noted in both eyes (A r E, and t \ W h ile
deposits around blood vessels w ere also seen (Cl. He under-
wenl а pars. plana vilnuclomy and focal laser w ill1 : improve­
ment in vision lo SLDBe in E w eek and 2(V20 in 1 month in
his litihl eye. Subset] LKm 11у Ihe left цуе suffered a viHesous
hemorrhage pnvnptilijj a vilred o m y with improvement of
vision to 2U/iQ. The vitrexjus deposits showed apple-urwn
birefringence on polarised m icroscopy w ilh Congo red I.F
His; vitreous; vascular endolhelial jjrowlh factor lovels лете
hiyhiy elevated. К is .Э-О-уеаг-oid Ь п я Ь р was examined i;nd
found lo h a w similar findings, requiring a vitrectomy in his
left eye. LSolh brothers w ere positive 1or C lu jH C ly transthyre­
tin mutation :D!VA change: 221 Л > ti), confifming familial
a n_,y loi do! it pol yneuropa I by.
iQflHftesy l?r. k i'inkir l-;rn. k.L|:-;ir|i|.: i. J lrt>mО'Нс.чгм l1!at. '
sulfur and potassium, may be found. Chondroitin С sul­
fate and carbohydrates specific lor hyalurouic acid have
been found.'1"'' Experimentally asteroid hyalosis has been
produced in galaclose-fed beagles which develop a retino­
pathy similar lo diabetic retinopathy.^1.
Asteroid hyalosis typically develops in later life and
most often affects only one eye. its association with dia­
betes mellilus Is a subject of debate given the significant
numbers with unilateral involvement.37' Лна Abnormal
vitreoretinal adhesions with vitreoschisis and anomalous
PVD have been documented by O C T 4 Vitrectomy is
rarely needed to restore vision but may be necessary in the
occasional patient who has unexplained visual loss.310'-1®?
In spite of a visible Weiss ring, these eyes may have adher­
ent residual vitreous cortex which should be soughl for
during surgery.
'Wl'jd-j'l/ HyalosiB 705

VITREOUS CYSTS
Vitreous cysts may arise in otherwise normal eyes., in dis­
eased eyes, or in associalion with remnants of the hyaloid
s y s t e m . : ' 'Ihose occurring in normal or diseased eyes
are typically round or lobulated, partly pigmented or non-
pigmentedr translucent structures Lying free in the vitreous
cavity (Figure 7.35A-D]. Cysts associated with the hya­
loid system are usually sessile, ncmpigmented gray cysts
attached to the surface of Lhe optic disc (Mg. 7.35C). Most
free-floating cysts probably remain unchanged for many
years, cause no symptoms, and require no treatment.-5' 1
Pigmented cysts located close to lbe retinal surface can be
mistaken fo ra pigmented tumor. 'Ihey occasionally inter­
fere wilh visual function, and in such cases aspiration of
the cyst or disruption with laser (D1 and D ll may provide
sym plo ma lie rel ief.16"W?l
The cyst wall In most cases is probably con]posed of
retinal pigment epithelial cells (E'lg. 7.35F and 1:).’а1^ '1'
Work and Mlllecchla found a single layer of pigment laden
epithelial cells on a basement membrane that resembled
iiruch's membrane with a lamina rarar lamina densa and a
thick collagenous layer (E'lg. 7-35 L and F). lhe cells were
positive for carbonic anhydrase (Fig. 7.35C ]r and on elec-
Lron microscopy showed microvilli, zonula adherens and
occludens, all features of retinaE pigment epithelial cells
(Fig. 7.3511). 'Iltere were premelanosomes (Fig. 7.3511,
inset, open arrow), which are of fetal originr and not pro­
duced postnatal ly in RPF cells, suggesting the cyst to be a
choristoma of the prlmaiy hyaloidal system with seques­
tered RPF cells.17h
METASTATIC CARCINOMA AND
MELANOMA TO THE VITREOUS
See C h a p te r 13.
7.3j Vitreous cysts.
A: Irregular, transluconL, bijpnented, free-floating vilreous
cysl.
B: Free-floaEing pigmented cyst located just inferior to Lho
mac ltI ,i .
C: NonpigmenLed cysl atlat-htid Lo lhe Optic nerve head.
D Lo H : This ,'i5 year old olher wise healthy Caucasian
wom an had noted a floater in her left eye since child­
hood. The floaiur was now tofistant and vision declined to
20^40. Л partly pigmenEed vilreous cysl was seen lelhered to
d e q u e 's canal And wns associated w ilh a Mjltend^rf'H dol
(D ll. Argon laser done Jo perforate Ihe cysl w all collapsed
Lhe cysl \D2 but Сhe cytt I hen hung in Гтол1 of her lijacuta
requiring a pars plana vitrectom y and cyst removal. The cyst
w all is made up of a hasemenl membrane w ilh pi gm ел I
laden cells consistent w ilh R R E (ToEuidine blue) (E and F ).
Plaining Lot carbonic anhydrase is positive confirming RF3t
-origin of 1he cyst cells (G)_ El-ecEron microscopy revealed
zonula occludens IH. arrow) and pre-me lanosomes iH, idsetl
that is considered to he feEal in origin suggesting arrested
development q f lhe biPE: cells.
Asteroid Hyalosis,
I and |: Asteroid bodies w ere sufficiently concentrated Lhal
a v ie w ot" lhe fundus details was d if f k jll in I his palienL,
who was com plaining of visual loss in the left eye ( I I .
А л^ iorj^rapliv (Jl. hOweArer, presided a clear v ie w of e v i­
dence of age-reLaied macular degeneialion anti subfoveal
neovascularization.
K: Ciross eye specimen showing asteroid bodies suspended
in lhe vilreous framework.
L: HistopathoEogy of asteroid hyalosis showing spherical and
о void PAS-posi Live ajfflorphous bodies suspended in the vilre­
ous framework.
L u i . i r l 'j : - ; . IjC u - H , !.’ t . M k I i . k 1' K - и гк . I-Li p:■r i 1 1 4vi Ihi p e r T r t l ^ t h a t i ( г и г и
( ^ l i l I i.i I r n L i к ц .- у I t'- H irk , I . M . л п г Е L . L . M i l к ч 4.1 li .1. 1 n L ^ L i n u n C 1: ■-:!
ln - ; r i j | j, i l J i i i | . : : . i ; . y u l в v iln iu u - ; l> s !. ( J f s t ilh .iln K jlG ^ y | 'J 'jd
a 2 5 - P JC J.i
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А. Ома T. 3ali ci H Ma i МП si a. impTr^d wwdbaDcn cl macJa' his е:юпЕ wlh ам- iras(yycl c^lsrertecmai С;йае. jraels^jeiCEn BoCfh'ijlKt-]! 1ЁК.253222-Е.
bDmcmso^ArcliCtiithdmdlS&i Ю9:Э57-б1 43. Bertsm^ -5йчап 'to. HhsoralxHiaiar^ni! detacfiTHfi ш *й bvpafairasoilat
5. Mm RG. ^ch-&]i' MW,Ja'ipo LU. Cflca- ос^.й'йле ш к ггр к им r nduadan cf me икваейн! ra o n Acf: Optiflialmol 19M:l it 639-7t
Ашейла! interlace u re^v.-.Sjh ОатГа1т12(Ю7;52:397-^21. 50. deBiBlrasEiWadi FE.Tne mu sec ге1га1'леак( arjiemesnd й vaianra. Crhlha^ic^1
G. sj j'] i H Fsmrez Jk pen А. fMxItVtJecdislarv йшг-л and m sja1aeosui Eye im fl l£/9l:53-&.
30(В(нЭ£7«-Вг 51 F'iK &. MaC.Gm C: elil. C^.i: cn-УLfldgng■!^Aisedrnrd le^elaоц'eKated
7. Drede1"i 'j Мзгдчег U. Gha^ti ^K. ec si. UHiehtj'-'ieia Irticfi sfflal c:№rena pl>]dKca3LlLia' (Ш-аггссду li£i:J4.15l3-o.
mmograptw. №t Mec200l:7:EC2-7 52. Fjctal:ai CM, -ilurii l VT. vJccca Atu&ec rels al ^sssis ■::№ id rai tieis; a ause of
5. toax D, S,*a:scfl EG, Un CF. et al Oplta ейеганв lie eras 1991;264. resj’s 1: '.linear теггат^аг^. Сртта!^ 1&7l:&B.GG9-72.
1178-Si. 53. vi e Alt toJa d el пз) ters wllBU riic l у йкз. Am J АиМЛш ' 98^ 9^.722-7
9. Ш и вд DJ Qi-цSW,Ah ® i e! a. U ir-scrx tttfidiDr al Irte 'л1гй ^ a;c netra. Semh 54. Etmei f,'. T is ll jcfescHe; faala re par la'd f си л £ J ^ l a iro M il 4:52IKG.
CtrthalTn &Ei5 l3:21L-.3 55. Adherg TM. '.t c Ji h-:te: i Ear/ CFhlhdind 1£10.' 3.13H2
1fl Fee: Rr. Wtoaefinsl m itrue, tmogrepi cal *a qIcas. 1г ^ й OptrtiHtori 1972:1' .EO H. 5S. ЛаЬегаТМ, Ehur CJ.Ge s J1W kiacu a' ho ts. An J Otf-Ta те l97^£:E£t-82.
II Feh AM. Fact № Su-fice stnture cf f e ocic nerrt x aJ '. Eipafi lav ггекйагк. An J 57. Л.1Ь mF. Ja+пЛЕ. K, ei aJ ESanaasecp с iluj'/ tre -гтесиз n m iis aeala.
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221 . Н ш те е Л Е Firteraitm H n ihssiUycfitieiTMUa foch Gdilhamsi 1567 73:
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224. rfe^Euis DA, Fa*ф к. Ш , fibae-Tiff Я irumar пж аи рептйпа prcile'alcn: лййо
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231. Ш Cn HL. Greaser kTu EtFjers IS. Aah alm e^ г diabeic пЬшлзсУа jereina
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232. Щ аПнгН^ЙанЁЙ GiHier’i s a l Acln ПатяЧ^т-д^ттэНгз ргепл га iremsij eE.
AjUi OpI’iffliriK^ 1Э&4;102:1370-5.
233. Ala-era R Koc^. E. зэег;пн (а eniN iiil m tra n s ;ndjced cy itt aUiral ancf pai с ce.
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234. Lea-J3. Ct gr- al яшае dsl epi^rd manbtanes n ai ani 'al iradd. Graels A'a: СП Енр
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235. bile b. Mifer H. SJ. L-jjerniarla enrehiupfareralitf i c^ed ?y itattiEa pUood
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Traumatic Retinopathy

B E R L IN 'S E D E M A (C O M M O T IO
R ET IN A E)
After a blunt contusion to the front of the eye, a patient
may experience aciJite visual loss caused by Berlin's edema
(commotio retinae).. In this condition the retina develops
a gray-white color that affects primarily the outer relina1''1
that may be confined to the macular area (I'igure 8.01A
and E) or may involve extensive areas of lhe peripheral
retina (I'igure 8.01 E>). In sonic cases the whitening may be
accompanied by retinal or p reretinal hemorrhages (figure
8.02A and ti) or subrelinal blood and choroidal rupture,
ihe retinal whitening in lhe macular area may clear com­
plete ly, and central vision may be restored (I'igure Д.01Е').
in other instances, loss of cenlra! vision may be perma­
nent and may be associated wilh no visible fundus change.
moLlling of Lhe retinal pigment epithelium (RPH). migra­
tion of pigment Into lhe overlying retina, or partial or f'ull-
Lhickness macular hole formation (Figures E and li
and 8.05). Jhe whitening in the peripheral retina may be
followed initially by pigment molding and later by atro­
phy of the R F t and migration of pigment inlo the over­
lying retina, producing a peripheral change thal clinically
and hislopalhologically simulates re Linit is pigmentosa
(Figure JJ.Q2F and F).l:-'
Fluorescein angiography typically shows no evidence
of retinal vascular or choroidal permeability alterations
in the area of &edinrs edema (Figure 8.01С and D ].3r&r8v!f
Angiography occasionally sho^vs a iransienl leakage of dye
from the retinal arterioles in the posterior pole or staining
at the level of lhe RFL [Figure fl.02Q .:u Following resolu­
tion of the outer relinal whitening, angiography may or
may nol show evidence of window defects in the ЙРЕ.
Vitreous fluorophotometry usually shows no evidence of
breakdown of the blood -retinal barrier.-1 Oplical coher­
ence tomography (OCTj shows increased densily of (he
pholoreceptor layers initially (Figure ti.OL |—L.).. followed by
lucent areas If (he receptors show cell death followed by
thinning of the receptor L a y e r . ' If the injury is mild the
receptors recover and the OCT findings resolve. Multifocal
elecrroretinogram (EiliC) shows depression of lhe ampli­
tudes in the affected area which recover if the outer seg­
ments regenerate or remain permanently affected if (he
receptors do not recover."1Light and electron microscopic
studies of Herlill's edema in humans as well as that pro­
duced experimentally in animals have shown thal the
outer retinal whitening is caused by fragmentation of the
.1M Ele rlin's ed em a ( c o m m o t i о r eti n a e).
A - D : This IQ -yearatti buy Mas struck in lhe left eye by а
rock. V ja la l acuity was 2(V70. K a le the jrone of wnltenfiafa
Involving 1he outer retinal layer |h the macula (arrows,; Д .
There was а 1дгНе retinal whitening in the far periph­
ery of" the same eye ( ll1. tojpbgrm hm wa£ normal and sbcAvffl
no evidence of rtilinal vascular abnormalities (C and □ .
E and F: Eleilin's edema o f lhe left гпч'эсиЗа in a 20-year-old
wom an lEl. Three days later I be edema had disappeared and
Lhe m acular function bad fpfcumed Iи normal (Рл
С —I: FhoLomicrographs of normal monkey relina lG), retina
4 hours (HJ, and relina 4B hours (fl after E>lunl Jrauma. So te
disruption of photoreceplor cells q u I w st^menls (arncsw, H:.
pykn(.LLi(.■nuclei in Hie outer nuclear layer '.l-E and I), and va c­
uolization of inner-se^ment layer of photo receptors farrow, 1^
paraphenylenediamine dyej.
I and K: A 2fl-ybar-old m ale was FiLL in the lefL eye by a
cricket ball. The fovoa was gray-while from com m olio be I
maintained an acuity o f 2tV20. An ОСГТ through Lhe commo-
Lio shows edema i^nd increased refleclivity Harrow, Ki al Lhe
affected photoreceptors compared to lhe adjacenl unaffected
receptors (arrow heads).
L: A darL penetrated Lhi-ь 11-year-old's sclera and choroid caus­
ing a ciiojoidal and subretinaj hemorrfia^E and а ^my-white
patch Ы commaLio (arrowl al its foveal edge, ipeclralis O C T
through the сотпгкЯю demonstrales lhe Lhkkening ot lhe l^'OS
junclion i.arrow1signifyinj^ irauma lo lhe pholoneceplors.
iЪ .incl hi fruin >i j |□lj гI v cL t L 4, i I 97Д. A n * c,in M c il t i! Лън.и kilicm.
All riiihils- гч'ькг^гч!..
photoreceptor ouler segments and acute damage lo the
receptor cells (Figure tf.tflG and h )/ j6,ls О С I', if done dur­
ing (his stage, will show increased reflectivity of lhe photo­
receptor layer and sometimes small clear spaces suggesting
disruption of the photoreceptors/' This loss of transpar­
ency is associated with no or minimal extracellular or
intracellular edema in Lhe retinal cells and wilh minimal
damage to the chorlocapitlaris.',:" ' 1 Other changes may
include breakdown of lhe outer blood-retinal harrier al
lhe level of the К I’Ll thal is usually re-established between
7 and 14 clays,1 if only the outer segments of lhe recep­
lor cells are involved, these will regenerate rapidly and the
retina may regain its normal appearance and function.
The OCT findings also normalise. A more severe contu­
sion may cause contusion necrosis and atrophy of the
outer retina (Figure S.02G and il) and a macular hole. Ihe
contusion damage lo the retinal receptor cells is probably
caused by mechanical distortion of the retina by deform a-
llon of the vitreous as well as hydraulic forces."'
® ®
 -SLibretiniiJ hemorrhage caused by choroidal rupture may
occasionally accompany Berlin's edema (see Chapter J).
Trauma similar to lhal which causes Berlin's edema may
also cause acute damage lo lhe KL’Li and serous delachmetiL
of (he macula [figure S.02CZ, and see Figure а.ОЛЛ-С),
as well as acule tears in the ETEi.:"
P O S T E R IO R C H O R O ID A L
R U P T U R E (T R A U M A T IC
C H O R O ID O P A T H Y )
Acute contusion necrosis of Lhe RE1^ or, more frequently,
a ruplure in Lhe inner choroid and !UJLi al lhe posterior
pole may cause a serous and/or hemorrhagic detachment
of the retina often in the macula or juxlapapillaTy region
(I'igure S .te ).1''12ё hi the case of contusion necrosis a
Localized serous detachment of the relina occurs atud a:igi-
ography shoe's multiple focal areas of dilfusion of fluo­
rescein from the choroid across Lhe damaged RPB inlo the
subrelinal fluid {Figure &,03A+Cj.2r 1^1Lowing resolution
of the detachment, varying degrees of RP£ atrophy may
develop. Tears in the RPfc rftay he evident after j contusion
jhjury,39 When Lhe re is a choroidal rupture, lhe localized
subrelinal hematoma typically overlies and obscures the
rupture (figure 8.03D,]; in some cases, outer retinal xvhit-
ening ( lier!in's edema) accompanies the choroidal rupture
(figure S.02K ).' [See discussion of contusion maculo-
pathy, Chapter S.) As the subrelinal blood disappears, the
rupture involving the choroid and RPE becomes visible
as a cur,-1]linear yellowish line wilh tapered ends concen­
tric wilh, bul often remotely Located from, the optic disc
[figure S.03L, G, E, and ]). lhe rupture typically involves
only the inner layers of the choroid hul may be full thick­
ness in some cases In many patients the choroidal rupture
es outside the foveolar area and visual acuity often returns
to near normal. Occasionally a macular hole or evulsion
of the optic nerve head may accompany an underlying
choroidal rupture.-'' :i Choroidal ruptures пиay occur after
minor trauma in patients with angioid streaks (see figure
3.3fiL).I J -1J
Intravenous fluorescein is helpful in detecting choroi­
dal ruptures partly obscured by subrelinal blood or in
detecting small ruptures that may be difficult to visualize
fl.02 Contusion necrosis of the retinal pigement
epithelium (RPE> and relina,
A —C i This man suslh ined M uni Irauma and ■ . isual loss in lhe
ri^bl eye. Note ouler retina) w hilcn iп-н, and retinal and pre-
nelinal blood (A a r d ЕЗ!-. Angiography (C) showed eslensive
staining caused by necrosis of [he R FEr ни well as Evidence
or t u n ilin e a r ch o io id aI ruplure Underlying the blood.
D: PnslconluHion m ncular hole i.arrow .I aild relinal and RLnb
aLrophy т л 1^-yедг-о Id ш й п previously si ruck in Lhe eye
wiLh а baseball.
E: .Macutar bole (arrowI adjacenL Го Lwo choroidal ruplunes.
1 be bole did nor (lo se follow ing viLrecLomv wiLh internal
EimiLLn^ membrane peel due lo contraction o f tbe underlying
Bruch's memhrane by Ihe choroidal ruplure.
F: Peripheral relinal and KL't dv^i'rcr.ilion t.uised by blunt
trauma. N o le narrowing of Lho relinal vessels and migration
of pigrftent inlo lhe retina lairow: si mi 1лг Lo lhal seen in feLi-
nilis pigmenlosa.
C: Photomicrograph of Lhe foveal area shqMfing local loss of
receplor cells-, cyslic degeneration, and chorioreLinal adhe­
sions (arrows! fo llrtyin g Irauma. The separalion of retina
from Ihe Kl-’fc is probably arliladilious.
H : Photomicrograph of Lhe foveal area showing more severe
poslcontusion atrophy of Ihe retina and КИЕ.
I anti J: Appearance in a 15-yeaf-old I year afler Eilunt iniuTy
from a Ljollle rocket w hich left him wiLfi severe con I u hit m
necrosis of lh e m acular retina and choroid U)_ Visual acuity
wan to u nl lingers ,H O.L> meLefs i2 toel.. O ptical coherence
tomo^rnplTV Of Ihe macula shows alnu-phic retina (Jl.
K: PicJure 2 monlhs afler an assaull in a 22-year-old male
showing several choroidal ruptures, resolving subrelinal
hemorrhages and organization into fibrous scars.
I I .lF id i, U i i H c J y u l U r . h n in c u R je C c h in : k . М ш г Н э - у o l
IJr. Кш1 МатЬгвд Ir.l
ophlhalmoscopically (Figure S.CJ3tr|. If the rupture involves
only the inner Layers, angiography will show large choroi­
dal vessels traversing the defect in the pigment epithelium,
linach's membrane, and choriocapiltaris (figjjje &.03K]
Angiography jnay demonstrate evidence of chorioretinal vas­
cular anastomosis al the site of the ruplure (figure S.03I.J.
Histologically, the choroidal ruplure involves al least
the choriocapitlaris, Bruch's membrane, and lhe R P f .
(Figure S.0311).1” '" The inner layers of Lhe relina overlying
the ruplure may or may not be damaged.""1
 Some patients ma\: develop visual Joss Within several
months of years after trauma because of spontaneous
bleeding or serous exudation from choroidal neovascu­
larization a rising al lhe site of an old choroidal rupture
(t-'igurv fi.03i and j)."' 1 ,|:' lhis neovascularization is
usually lype ]] ,ind often produces a pigment halo at the
sile of ingrowth of lhe vessels into [he subsensory retinal
space. Similar delayed neovascularization may occur at
tbe site of a choroidal rupture caused by the impact of an
intraocular foreign body, or at a surgically produced cho­
roidal perforation made during the course of scleral buck­
ling for retinal detachment.iJ Lxtensive organization of
subretinal blood may produce a variety of disciform scars,
some of which may simulate a melanoma.
Gass has seen several patients who., following contu­
sion injury lo the head, have developed a typical ophthal­
moscopic and angiographic picture of idiopathic central
serous chorioretinopathy within several days of the acci­
dent. Profcably these are patients predisposed Lo this dis­
ease who, as a result of the emotional stress rather than
direct trauma Lo the eve., develop a detach men! lhe prog­
nosis for spontaneous recovery is excellent.11 15
(Ir03 Postco ntiltsi(in m acn lop at hy (cho roida I rupture).
A—< : Venous jelinal deLachTimnl in lhe m acuJa noted imme­
diate! у a[Stir severe Ыип1 contusion (o tbe rigfiL eye in a
7-year-old girl. Anfjio^rams show evid en ce of multiple focal
areas of leaking of fluorescein from choToidal Vessels into Lbe
s tib rd iral iluid.
D -F: Subm.acuJflT hemorrhage jrtfondaTy to chlOjoidal
rupture foll<Jwmy a contusion lo [he ri^hl eye in л youn^
adult Hi:. Several weeks Liter [he subreLinal bio<id has
cleared (Ej. Note [he small choroidal TupLure (arrowk
^jraograpby revealed i'luomscence in lhe region й( the с 1ш-
noidal rupture <Fj.
fj: Lar^e choroidal rupture in iic? pnpillomacuLLr bundle
nu^ion o f .1 2 1-year-ofd man w h o experienced loss of vision
several mtjrcLhs previously in if l automobile accident. The
visual acuiLy al lbe- lime of Ibis p h a lc ^ a p h was 20/'iD.
H : HlslO patholojy of a broad t boroidal rupture in tbe pap-
illom acular bundle of another patient. Mote the hyperplasia
□f Lhe retinal piemen I epithelium at Lhe sile of lbe break in
Bruch's membrane I arrow).
I: A hemorrhagic detach men I o f lbe macu!a secondary lu
l horOldal neovascu lari zal ion (агпмИ developing at lhe hire
of an old choroidal rupLuie in- a 34-yuar-old man who bad
sustained blu п-L Lra;uma lo Lbe eye 2 years prtetfjoudy. Al I tail
Lime.. he had evidence ol a subrelinal hemorrha^t1 that bad
ни I sequent ly cleared. Approxim ately й weeks bfijfcre LEiis
phctlo^raph Lbe paLient experienced sudden loss of cenlral
vision in his left eye.
|-L: Serous deLachmenl of lbe mtina caused № Lyfwj II sub-
relinal choroidal neovascuEaJ- membrane I arrows I arising in
old chom tnal rupture.
Posterior C/tifjjtfriftJ jViici fi;,;jv‘ ‘tT rtn im fflc С i4urp i& rfttfh r/J 7 19
M A C U L A R C O M P L IC A T IO N S O F
P E R IP H E R A L C H O R IO R E T IN A L
C O N T U S IO N A N D R U P T U R E
(S C L O P E T A R IA )
Contusion and rupture of lhe peripheral choroid and
relina caused Ъу л high-velocity missile striking or pass­
ing close lo but not penetrating the globe {sdopetaria)
Ё5 an infrequent manifestation of nonpenelraling ocular
trauma/ 6 A large, often ragged retinal and choroidal
break associated with surro Lin ding retinal while ning and
varying amounts of blood are the cardinal fundoscopic
features (i'igure S.04A-FJ. The white sclera may be visible
within ihe break. In spite of (he break in ihe relina, L'heg-
matogenous detachment occurs infrequently. Loss of mac­
ular function may occur acutely because of extension of
tbe damage posteriorly [Figure 8.04 A), associated macu-
Ear holer,u or it may develop many months after the injury
as a result of vascular proliferative and exudative changes
occurring within the peripheral scar (Figure S.04C-L).
I.ate fundus appearance is characterized by plaque-like
fibrous proliferation wilh variable amount of pigment
with scalloped margins, l he pathogenesis of lhe loss of tis­
sue seems to be partially from dissolution and partly from
retraction of lhe relinal and choroidal tissue.'1^ Ketinal
detachment is uncommon due to scouring and fibrous pro-
Eiferation lhal follow the injury.'^"’"'1
8.114 Contusion injury to the peripheral retina and
choroid.
A -F: Sdopetaria w ilJi rupture uf Ihe peripheral choroid and
iujlina c.i used by л bill kit pa&jitig adjaccnl Lo Lhe eyth wall.
N ole Ihe stefiale choroidal rupluFes, scarring, and s-ubrelinal
□lood ^ te n d in g inlo Ihe m acUyi (A| from Lhe peripheral rite
oE с hori ordinal rupluna IH-). Sis months; JaLer: nolej the exten­
sive scarring porieri<*rlv and Ul a r d peripherally in the
area c f relinal IE: artd choriojolinal ddfiistehdq .l:!.
G - K : Delayed Ions ol virion OLCUTrLid in ihis yotERg w om an
who developed ли ex-udalive njliital delachmen] it! caused
by л peripheral lar sub reLin ;il m ass iH l several
years. followm jj a contusion injury Го lhe relirtn mfwolunnpn-
rally. The subnet ina I ex u d aLe resolved lo llowing Lransscleral
Lryopexy 11 and |j. 5i\ т о л Lhm later she noted mild melamor-
phopsia Laused I jv traction of an e p inelinaI membrane lhal
ever a period of several months parlfy peeled from the relinal
surface fj ami Jt).
L: A lar^e /one rjf" relinal and relinal pigrnertl epithelium
atrophy w ilh bone corpuscular pigmental ion (arrows^ devef-
oped over a period of seW>ta! years following ал inferotem-
pural conLusfon iп-jLiry In lhe right eye.
IL, сииМшу иГ 3>г. Млиг itt i . k.itib.i
P O S T T R A U M A T IC M A C U L A R H O L E
A N D F O V E O L A R PIT
Jhe foveolar pari of lhe relina is exLremety thin. and blunt
Иа&ты may cause a full-lhickness mgtular hole by1either
one or a combination of mechanisms: ( I j contusion
necrosis: [2J subfoveal hemorrhage; and (3) vitreous trac­
tion. A macular hole may accompany or soon develop in
patients With severe Berlin's edema, with a subretinal hem­
orrhage caused by choroidal rupture [tigune 8.L1S), or in
a whiplash separation of the vitreous from the relina (see
Chapter 7 for additional discussion of the pathogenesis of
macular hole).
Cenlral macular pits identical to those seen in patients
following sun gazing have been described following
blunt trauma to lhe eye and whiplash injuries {llgure
S.05] I ) . '1' i;i E.oss of visual function occurs infrequently as
Lhe resull of whiplash. The syndrome of whiplash mac-
ulopathy consists of a history of flexion-extension of the
head and neck trauma without direct eye injury-, imme­
diate mild reduction in acuity of no worse than 20/30 in
one or both eyesr gray swelling of the foveal zone, and the
development of a 50-Ю0-| m-diameter foveolar pit. The
retinal opacity disappears, and the acuity usually returns to
20/2U, but the pit and its whitish borders remain. Iliere
may be a slight posterior vitreous detachment, and there
cnay be a micro-operculuan. Fluorescein angiography
either is normal or may show a Liny focal area of early
hyperfluorescence.53 Grey described a similar pit develop­
ing in three patients who experienced direct trauma to the
eye and postulated that any agent, either physical or toxic.,
that causes seleclive cenlral photoreceptor loss will give
rise to the appearance of a cenlral foveolar pit. ■ ' Small pre-
foveal vitreous wisps* opencula, and full-thickness macular
holes are other changes that may be caused by trauma-
induced alterations al (he vitreous-macular interface.' "
ihe tnechanism of traumatic macular hole could be a
primary concussive break or dissolution of cells result­
ing in a cystoid change that broke down leaving a defect.
Spontaneous closure of traumatic macular holes is well
documented and hence waiting 4-6 months for this may
prevent unnecessary surgery. i6"bl
Patients with trauma-induced macular holes not associ­
ated wilh a large rim of relinal delachmenl. or if accompa­
nied by pigment epithelial atrophy, are probably noL good
candidates for macular hole surgery because of contusion
damage to lhe retina surrounding the hole (see discussion
of macular hole in Chapter 7}_f,J-< ?M
| infarcts, however, in fal embolism are usually smaller and
F U R T S C H E R 'S R E T IN O P A T H Y
lij Ilowing severe compression injury lo the head or trunk,
the patient may experience visual loss associated with a
peculiar retinopathy in one or both еувь10 The char­
acteristic ophthalmoscopic findings in Purlscher's reti­
nopathy include multiple patches of superficial retinal
whitening and retinal hemorrhages surrounding the optic
.U Tfatimalic macular hole.
A and R: Subnet=na! f^emtjrrhage,. macular hois faitCW, A.
Lind choroidal ruplunt? (arntiv- til caused Iзу -a blunt injury lo
Lhe суп1.
С: Mricular hole and choroidal rupture (atfowl in л 7-year-
ukl hoy previously slruck in the left eye.
D - G ; Large m acular hole and hrofid choroidal rupture in
я 35-year-old wom an 1DJ. Angiography repeated absence
Dt choriocapiITaris- but preservation -ol some a i lhe large
choroidaE vessels (arrow,. Ej in the region ol the hole. Late
angiograms showed fluorescein s-taining in lh e region of Lhe
choroidaE rupture as w ell as at several areas of the hole (F>.
Thrrty-s-iж months later Lhe m acular hole had enlarged and
Lwo additional holes bad developed superior Lo Ihe m-atula
(arrows, Cl.
H-K: im nll lamellar macular hole or piL ^arrmvi in the rignl
eye afijnulating solar гласиlopalhy :Hl and 1ulI-thickness niafu-
lar hole in Ihe left eye 11■of ,i 4b-year-old chronic aioohohi.
who had sustained multiple episodes ol trauma to both eyes.
nerve head, Which usually appears normal [E'igure S.OfrA.
H, Gr 11 and E.J. The while patches are localed mainly in
the area surrounding the optic disc and often do not
extend into the center of Lhe macula. ETart of the retinal
whitening appears to lie anterior to the retinal vessels. In
soute cases there may be confluence of the white patches
{I'igure 3.06G}. Fluorescein angiography in milder cases
may show leakage of dye from lhe retinal arterioles, capil­
laries, and venules in the area of the white retinal lesions61'
and, in more Severe cases, may show evidence of arteriolar
obstruction and leakage in the region of the white patches
(I'igure jjjQ&C and E)J.':''r'6 Jhcse patches and hemorrhages
disappear, but the patient may be left with some loss of
cenlral vision and oplic atrophy (figure 3.06E and E:).
'lbe pathogenesis of Purlscher's retinopathy is con­
troversial. The white patches that are oflen referred Lo as
exudales are probably focal areas of ischemic retinal whit­
ening. Angiographic findings of retinal aneriolar leakage
in some cases of Kerim's edema10 as well as in some cases
of [:urtscher,s retinopathy"'-11'' suggest lhal acute endothe­
lial damage related to trauma may predispose the retinal
vascular tree to inlravascular coagulopathy or granulocytic
aggregation'" that may be the cause of multiple arteriolar
obstructions. Air embolism in patients wilh chest com­
pression1"' and fat eLTibolism in patients wilh long-bone
fractures"' have been implicated as causative factors in
some cases of E’unscheKs retinopalhy. The white retinal
are often situated more peripherally in the retina.01'*"0
'lbe characteristic restriction of the retinal lesions in
Purlscher's retinopathy to the posterior retina may be
related to the unique anatomy of Lhe blood supply of the
peripapillary and macular areas. Most of the relinal vessels
lie within the nerve fiber layer except for iwo capillary lay­
ers, one lying in the ganglion cell layer and the second in
the inner nuclear layer with anastomosis between them.
A third capillary layer exists in the macula, lying between
these two layers, and a fourth layer of слрИIJirLe-s exists
within the most superficial aspect of lhe nerve fiber iayer
around the disc. Jh is fourth layer of peripapillary capillar­
ies extends for two disc diameters nasal to the disc and for
(bur disc diameters temporal to the discr although for only
one disc diameter along the horizontal meridian."1Uni ike
Lhe other capillaries En the retina, the peripapillary capil­
laries have fexver feeding arterioles and fewer anaslamo-
ses. ' As a result they may be Enore susceptible to embolic
occlusion. HEstopa lho logic e\a mi nation of an eye 34
months nifter development of L’urlscher's retinopathy has
demonstrated Inner retinal atrophy compatible with reti­
nal arterial occlusion."
Л fundoscopEc picture virtually identical to lhal of
Purlscher's reti nopal hy may occur in palienls with ceEilral
retina] artery obstruction, acute pancreatitis. Eupus ery-
themalosusr dermalomyositls.. scleroderma, and amnEolic
fluid embolism (see discussion in Chapter 6).
R ET IN A L A N D V IT R E O U S
H E M O R R H A G E A S S O C IA T E D W IT H
S U B A R A C H N O ID A N D S U B D U R A L
H E M O R R H A G E (T E R S O N 'S
S Y N D R O M E )__________________________
Jerson described vilreous hemorrhage occurring in
patients with subarachnoid hemorrhage and attributed it
to л sudden increase in venous pressure lhal ruptures epi-
papillaiy and peripapillary capillaries.14’-7'* Others have
attributed the intraocular hemorrhages lo a rapid increase
in intracranEa! pressure causing compression of the cen­
tral retinal vein and its choroidal anasiomotEc channels/'
Approximately 20% of palients suffering either sponta­
neous or posllraumalic subarachnoid or subdural hem­
orrhages develop intraocular hemorrhages that in most
cases are confined to lhe juKlapapillaiy and macular areas
(bigure Й.07А-1}]/41;1 Inlraretinal and subretinal bleed­
ing occurs primarily from the optic disc and retinal blood
vessels. The intrarelinal hemorrhages can be superficial
or deep, blot or fiame-shaped. Often some of the deep
.О*-. T u rtsch e r's re tin o p a th y,
A -F: Tinib 4 5 -year-old m an noted blurred vision riILct [аГЕ-
injj out of a lacing lioal iriц at high speed. Visual acuity
was 2-0/30. Note patchy swelling o f Lhe relina surrounding
the optic nerve head (A). The w hile material appeared lo
Eie mostly anterior lo [he retinal vessels. Il was associated
w ilh superficial hemorrhage. N o le relative rirtjj. ol Lhe
macula IB). Ttiere were no Lesions in [he peripheral tundus.
AiteriovienouK-phase angiograms sfnowed I nek of filling and
obscuration of the capillary bed in lhe region of the w hile
lesions (Cj and later showed evid en ce of fludresdeih Leakage
into ltie relina (D). Ten days JaLer there had been considur­
able clearing o f the retinopathy (El. Five months. Liter there
was mild lemporal pallor (F). Visual acuity was 2EV3D.
( j —E: This 23-year-oLd man was thrown Ircmri his car and slii;-
Lained л basilar and ethmoidal Гглс'ипе. Note the Jar^e area of
iscbumic whitening and hematomas that probably lie benealb
the internal limiting membrane fC and HJ. T lie left eye was
normal. S o le lbe sufwrficial jelini^l tear iarrow, 1) and traction
lines extending through the гласи la approximately 5 weeks
later.
|-L: This patient received cardiopulm onary resuscitation
following a motor vehicle accident. Bilateral subconfunc-
Lival hemorrhages w ilh prorating I ЬегтцаггЕиуе and neive
fiber irrfnrcts in Ihe right eye and peri pa pi I.Ja n 1 retinal w hit­
ening and retina! hemorrhages in the left eye seen 2 weeks
□OsteMSrt. Visual acuily was 20/20 in lbe righL eye and 4/2 00
in Lhe lelt eye. H e had a Lefl traumatic optic neuropathy in
addition and lhe vision remained at 6/200.
|J—L, IUHjrifcrt 117 Dr I 1,1. I ^iLTntHir^, Ir.
intraretinal hemorrhages appear pelalloid with feathery
margins due lo dissection of blood into the outer plexl-
form layer [E'tgure 8.07G-]1. Intrarelinal and subretinal
bleeding occurs primarily from the oplic disc and retinal
blood vessels, lilevated mounds of blood eElher beneath
the internal limiting membrane of the retina or in lhe sub-
hyaloid space may occur (]:igure En mosl cases
ihese hemorrhages clear spontaneously and visual func­
tion ts unaffected. Occasionally the vitreous hemorrhage
fails to clear and vitrectomy may be necessary lo restore
vision.llJ"e!’ The surgeon may find some evidence of reti­
nal blood ve&se] and RPE damage (Figure S.07E and I ).
Itie amount of blood in the eye is ttol necessarily related
to lhe severity of lhe subarachnoid hemorrhage.^" A peri-
macular retinal fold may develop after resolution of
the sub internal limiting membrane hematoma in some
patients/ Eipi retina I membrane in the macula is lhe most
common sequela of'E'ersons syndrome but is nol associ­
ated wilh visual morbidity."'"' Because severe p ro liferate
vitreoretinopalhy occasionally develops, patienls should
be monitored periodically with ultrasonography while
awaiting clearance of lhe blood, and prompt vitrectomy
carried out if needed."^
'ierson's syndrome is seen Tvilh ruptured aneurysms
(i'igure 8.07G-J), arteriovenous malformations, head
trauma, including gunshot injuries, post epidural injec­
tions, and post endoscopic ventricular colloid cysl removal
and dissecting aneurysms of the vertebrobasilar sys­
tem.'' ' 1Children with subarachnoid hemorrhage are less
likely to develop vitreous and retina! hemorrhages com­
pared lo adults. Ihis may be due Lo belter resilience of
the vessels in children compared lo adults.
H E M O R R H A G IC M A C U L O P A T H Y
C A U S E D BY S U B A R A C H N O ID A N D
E P ID U R A L IN jE C T JO N S
Patients may develop multiple scotomas caused by retinal
hemorrhages in one or both eyes tmmediately after lhe
injection of oxygen inlo the subarachnoid space during
the course of myelography,''11 or following epidural injec­
tion of corticosteroids for relief of back pain.'17'’^ These
hemorrhages often occur as the result of bleeding from
the deep relinal capillary plexus and cause a pelalloid pat­
tern of blood with tapered edges centrally surrounding
the center of the macula. Sudden elevation of the cerebro­
spinal fluid pressure and elevation of retinal venous pres­
sure are the most likely explanations for the hemorrhages,
some of which may occur from lhe superficial as well as
the deep retinal capillaries in a pattern similar to that seen
in i'erson's syndrome, lhe prognosis for the spontaneous
return of normal visual function is good.
P O S T C O N T U S IO N
N E U R O R E T IN O P A T H Y
lllunl trauma to lhe eye or periorbital region may cause
acute visual loss associated with a swollen optic disc, and
optic disc and retinal hemorrhages that are usually con­
fined to the posterior fundus (ligure fl.OSA-Cj. Some of
the blood is derived from lhe deep plexus of retinal blood
vessel^ And may extend inlo the outer plexiform layer of
Henle to form a radiating pattern centrally, lhe fundus
picture may simulate lhal seen in patients with papillo-
phlebitis, with lerson's syndrome (see I'igure 3.071]-]),
S.07 Terson's syndrome,
A - 13: This 4.i-year-old и ш д п noted v-isual bJurfiny in both
ey&s soon after admission ha lhe hospital because til я sub­
Arachnoid hemorrhage. NoLu lhe multiple darker supedicial
hubinternnl limiting m e m b ra n e relinal hemorrhages ■arrow.,
fighter ^ubnliital hefticfrrfiHgpS, and opiic disc edema in bcuh
eyes lA-C:. Fluareajcpin angiography revealed evid en ce of
opiic disc edema |D).
E and F: Hi is 50-year-old man experienced an acule hyper­
tensive crisis, headache, neck pain, and coma. Fresh superfi­
cial jjEobuEar ju>tapapi!lary hemorrhages w ere noted in bolh
eyes. Six days Ealer he had bilateral dense vitreous hemor­
rhages. O v e i Lhe subsequent b увдг* his vision was hand
mol ions o nly because of Lhe persistence o f the vilreous
blood. W h e n seen at Ihe Kascom Hi Ime г Eye Inslilute neither
fundus could he visualized because ol old vitreous blood.
He had л vitTBctolrry in both eyes. I^jsloperatively, his visual
acuily in the rijjhl eya was 20/25 and in Ihe left eye was
20/40. The righl fundus was nofmal except for hypertensive
relinal arterial narrowing and two white choroidal vessels in
Lhe m acular area iE: . In Lhe lefl fundus, similar <horoidal ves­
sels w ere associated w ilh a zone o f retinal pigment epi 1ЬеП л I
alrophy in- the macula (J-:.
G —|: This 4В-уеамэ№ man developed sudden severe head­
ache and losl consciousness transiently w hile driving his
Irudc. He was difficult Lo rouse when examined in tfie emer­
gency room. Л computed tomography scan Erf the head
showed subarachnoid hemofrhage itnd ma^nelic resonance
angiography confirmed an anterior com m unicating arlw y
aneurysm. His visual acu ily was 20/70 in lhe night eye and
20/20 in lhe lefl eye a I Lhe hedside. when examined after
a coil was placed in lhe aneurysm. Multiple preretinaE and
deep retinal hemorrhages, some o f which were petaEloid
in Lhe о и lei plexiform layer1 ,, w ere seen in lhe rijjht eye I Cl
and H l fhe lefL eye iiarf a few deep relinal hemorrhages.
Note similarity o f the dislnbuLion of lh e iiemorrhniges lo lhal
shown in Figures B.07K and L and в. OS A and №. Ten weeks
Ia Lei his vision was slill .20/70 in lEie righl eye, and the hem­
orrhages w ere clearing, w ilh a residual small proretinal hem­
orrhage o u t his fovea ijl. O ptical coherence tomography
confirms :he proretin-al location of lhe hemorrhage anti rules
out a m acular hole ■:!.
Idiopathic unilateral deop retinal hemorrhages.
К and L: U nilaleral visual loss an il mu I Li pie deep reLi-
naE hemorrhages occurred in the left eye of this otherwise
heallhy young adull who j^ave no history of Irauma or ifl-
ness. NoLe Lhe pelalloid arran$=omenL of lhe hemorrhages Lhal
й ro t ably are localed in lhe outer plexiform layer.
I К .ммI I.. Cuu-rtfciy ul J>r. ,V. n.i'icL’ li.iEjb.i
and following epidural injections. A sudden elevation in
the cenlral retinal venous pressure caused by the trauma is
presumed lo be important in the pathogenesis of the optic
disc and retinal hemorrhages. A similar pattern of in tier
and outer retinal hemorrhages occasionally occurs unilater­
ally in healthy patients, wilh no explanation for them (see
I'igure S.07K acid I.).

S H A K EN - B A B Y S Y N D R O M E
Shaken-baby syndrome results from severe shaking of
infants, oflen as a form of punishment. rlhe signs and
symptoms are nonspecific and may mimic infection,
intoxication, or metabolic abnormalities. Ihese include
(1) bradycardia, apnea, and hypothermia; (2) lethargy;
irritability. seizures, hypotonia, full or bulging fonta­
nel k, and increased head size; [3] scattered superficial
retinal hemorrhages, dome-shaped subinlenia] limiting
membrane or suhhyaloid hematomas, and cotton-wool
patches; and (4J skin hruises.'' 111 A history of a recent
minor accident or shaking in an effort lo resuscitate may
he obtained in some cases. 'Ihe retinopathy may simulate
[hat seen in Terson's syndrome, I’tirtscher's retinopathy, or
central reltnaI vein occlusion (E'iguie S.OESD-L). [.ate fun-
d<racopic changes include a circular retinal fold that may
create a crater-like depression in the macula and traumalic
retinoschisis.H?L' Lt''i ]0:t ll,| M’ ]he circular retinal fold may
he a product of abrupt xilreoretinal iraclion associated
with shaking,11,1 vitreous traction after partial separation
of the vitreous in the central macular region,11 or contrac­
tion of the in ten t] limiting membrane or the posterior
hyaloid membrane after resolution of a subinternal limit­
ing membrane or sub hyaloid hematoma. Laboratory find­
ings include bloody cerebrospinal fluid and subdural lap
anti, in almost all cases, computed tomographic evidence
of al least one of the following: subdural hemorrhage,
subarachnoid hemorrhage, or cerebral contusion. 1" 'lhe
prognosis is poor, and many children are left with severe
neurologic and develop men La] defects, including visual
deficits and in some cases blindness.
The histopathologic findings in the eyes of these
patients revea] evidence of intraretinal blood, subhyaloid
and subinternal limiting membrane hematomas, as well
as blood in lhe subdural and subarachnoid spaces around
fi.00 P o s tc o n tu s io n h e m o rrh a g ic ne tiro re tin o p a th y.
A-С: This young wom an experienced lass of vis-ron aller
being s-Etoned ayainsl a wall. Note ihe swollen optic disc,
and s LifJt'rlit: iiiJ and d w p relinal hemorrhages, w h k ti gradu­
ally d e a rth . Vlild opIiL atrophy was assoc ia led w ilh 20/50
acu ily.
S h a k e n - b a b y s y n d ro m e [n o n a c c id e n ta l trau m a )
D and E: Shalffin^oaby syndrome w ilh m ultiple supndicial
n 1! in ci I hemorrhages; farrow, [J in a ti-rnonth-old in-fanl.
F: Photornic^feadh of subinLuTnal limiting membrane hem-
□IThajje in an iril'di>L who died Ol coinpi-l it:л.(':с.5-пs of thлken-
baby syndrome.
G and H : Gross findings in a 42-tveek-aId infanl with exten­
sive intrarelinal ttemgjrhageb and papiIIedema [G ) and blood
in lbe perineural shealb of lbe apliL nerve (ап-ow,. Hi. Sim ilar
changes were present in bolh eyes.
I and J: } 'hoLr>m i crugriaphs of another phys'ta lly abused
infant with gross findings similar lo G and H in botb eyes.
N o le peripapillary subnojnaj bEood upp*?r arrow, 11 and
hemorrhagic infarct ion of lbe reLina ■! . 1here was bEood in
Lhe subaradm oid and subdural space: dow er arrow. I) in bolh
eyes.
К and L: KeLina' hemorrhages are widespread and exlend up
Lo lhe ora serrala. W idespread uxLenl of relinal and prerelinal
hemorrhages rJoe.Lrmonted on Kelcam images (L).
the optic nerve- (l:igure j | L p s F - J ] |(||.]СЧ-ИЫ1?. пя -]^f su^_
dural and subarachnoid hemorrhage in the oplic nerve
may be subtle and the only manifestation of the shaken-
baby syndrome. Special stains for iron may be helpful in
delecting evidence of previous blood in these areas occur­
ring many monlhs before the eyes are obtained at autopsy.
The finding of retinal hemorrhages in a child with sus­
pected injury is more likely to be caused by shaking than
by blunt trauma,'''1-1'*1-1'-' 11s and it is an important predic­
tor of neurologic injury.113
ShnJcriT-WilklH urrj 729
R ET IN A L V E S S E L R U P T U R E
A S S O C IA T E D W IT H P H Y S IC A L
E X E R T IO N (VALSALVA
R E T IN O P A T H Y )
A sudden rise in inLrathoracir or inlra-abdominal pressure-
particularly iisl a closed glottis [Valsalva's maneuver)
during lifting, bowel movement, coughing, or vomiting,
may cause a rapid rise of intravenous pressure within lhe
eye and spontaneous rupture of superficial relinal capil­
laries in otherwise normal eyes or in eyes associated with
acquired relinal vascular аЬпогпыIities (diabetic or hyper­
tensive retinal angiopathy) or congenital retinal vascular
disease (relinal telangiectasis and congenital relinal artery
tortuosity) [E'igure h .o y )."1'" 1-4. Sudden loss of vision may
result from hemorrhagic detachment of the internal limit­
ing membrane, vitreous hemorrhage, or. if bleeding occurs
near the foveal region, dissection of blood beneath the
relina. lhe aulhor has seen one moderate myope develop
extensive choroidal hemorrhage following violent inces­
sant vomiting (I'igure Ь.ОУА and b}. ihese patients typi­
cally have a circumscribed, round or dumbbell-shaped,
bright red mound of blood beneath the internal limiting
membrane in or near the central macular area (I'igure
6.0У1}, b H, and J). A glistening light reflex ts present on
the surface. A few fine striae indicative of wrinkling of lhe
in ten t! limiting membrane may be present on (tie surface
of the hematoma. I'arL of the blood turns yellow after sev­
eral days, lhe shape and color of these lesions may sug­
gest an intraocular parasite (E'tgure 8.03D and Ei). A fluid
level caused by settling of the formed blood elements may
develop soon after the hemorrhage (Ktgure Й.0У1Е and |).
As the blood resolves, lhe serous detachment of the inler-
rmE limiting membrane may persist for several days or
weeks (E:igure Й.0УЕ).1" Spontaneous reattachment occurs,
and the appearance of lhe macula and visual acuity usu­
ally return to normal.
Occasionally a Small (less than one disc diameter},
roundr prerelinal hemorrhage centered in the foveal area
occurs.'■'n 'Ihe surface may show multiple yellow-wbtie
dots simulating that of a strawberry (see figure &.0У1}).
its surface usually does not show a reflex suggestive of lhe
presence о fan internal limiting membrane. It may repre­
sent a small nimounL of blood lying between the internal
Limiting membrane and the posterior hyaloid interface. En
addition, patienls with these small central Lesions often
have a thin layer of blood lying beneath lhe relina in (he
pa и macular area. Complete recovery of vision usually
occurs spontaneously. Jn unusual circumstances where a
subinternal limiting membrane hematoma is responsible
for visual loss in the patient's only normally functioning
eye, neodymium-VAC iaser disruption of the internal lim­
iting membrane allowing the blood to gravitate into lhe
inferior vitreous cavity may restore central vision more
promptly [E'igure 8.03К and E.].1^ '1:MSubinternal limiting
Valsalva retinopathy^
A—С : This healthy 5?-year-old m yopic w om an developed
sudden onseL of blurring of vision of lhe righL eye after sev­
eral EjouEs of vom iling ГсзI low ing food poisoning. Shy had a
relinal detach menL in I his repaired by а scleral buckle pre­
viously. Нет visual acuity w as 2(У40 with extensive ch oro i­
dal hemorrhage iA and Hi. Four w eeks later Ihe hemorrhage
had cleared com pletely and 1he* visual acuity returned lo
10/10
D and E: This youny man, who was on a respirator because
of acule respiratory distress syndrome of unknown cause,
experienced I os-5 of central vision in Ehe left eye. He was
referred 1o the eve clin ic because of a suspecled inlnaotular
parasile. \ o te Ihe superficial retinal blood lhal probably lies
beneath the inLernal limiting n tm h n m e (Dl. Angiography
revealed no relinal or choroidal vascular abnorm ality 1EJ. The
E)iood clearer], ап-d lhe visual acu ily returned to normal.
F and G : Ib is 56-year-old man was Iifling a Eieavy box w hen
he suddenly losL cenlral vision in his ri^hl eye 3, monLhs
before examination at Hascom Ralmer Eye Institute. His local
physician suspected an intraocular cysticereus larva. Visual
acuity was ^Ll/200- Nole Ihe paras itc-i ike shape of lhe suEnn-
ternal limiliiTg membrane blood IF . Angioyraphy revealed no
evidence of retinal vascular change (GX
H and I: Serous and hemorrbaytc detachment of (be internal
Limiting membrane of lhe retina in a 33-year-old man who
experienced sudden loss of vision during a. bout of vomiting
IH). Visual acuity was 2Q/B0. Tbene was no other evidence of
relinal vascular disease. Three monLhs later a shallow serous
delachmenl of the internal limiting membrane remained I .
Vis ua I 4icui(y was 20/1 5.
J: This .30-year-old wom an had a cardiac anesl during sur­
gery on her Liand. Cardiac resuscilation was successful and,
when she regained consciousness 2 days laler. she noted
bluned vision in the right eye. Three weeks Ealer hw visual
acuily in Lhe right eye was 20/40. Ijhe had a subinlernal lim­
iting membrane hemaloma in Lhe m acula and blond in Lhe
vitreous interiorly in lh e righl eve ц]. The LefL eye was nor­
mal. W iih in 4 months lhe blood cleared and her acuily
returned Lo 20/20.
К and L: Иге and posl Yaj} iaser disruption of subhya.loid
hemorrhage to speed up resolution.
К and L.. <uu rlusy cl Or. Suj .1 n iMulinoiUSki
membrane hemorrhage and prereLinal hemorrhage identi­
cal to Lhal fust described occasionally occur in the normal
individual in the absence of a clear-cut history of unusual
exertion or Valsalva's maneuver 1,!i |!J !iome pal tents may
have evidence of retinal vascular disease, for example dia­
betes or hypertension (figure 6.26C,]. Other apparently
healthy palients may give a history of multiple previous
episodes of loss of central or paracentral vision secondary
to spontaneous reliLtal hemorrhages Their family mem­
bers may give a similar history.1-1 lortuosity of the sec­
ond- and Lhird-order retinal arterioles may or may not be
present in these patients with a familial history (E'igure
6.01A-C). No specific hematologic disorder has been
described in this condition, which is probably inherited as
an autosomal-dominant trail. Recovery of vision is the rule.
E V U L S IO N O F T H E O P T IC D IS C
A forceful backward dislocation of the optic nerve from
the scleral can at can occur under several circumstances,
including: [1] extreme rotation and forward displace­
ment of the globej [2] penetrating orbital injury caus­
ing a backward pull on the optic nerve; or [3] sudden
increase in intraocular pressure causing a rupture of the
Eamina crib гола.: 11 13 This ] alter mechanism might be
more appropriately termed "expulsioEr rather than "evul­
sion." In all cases a Lear in the lamina cribrosa and nerve
fibers al the disc margin occurs, this tear may be partial
or complete and may be associated with massive intraoc­
ular hemorrhage (E-'igure tf.!0G and JE) or only minimal
bleeding (Figure 3 .ЮА-С.. К, and I'}.1' ' In the latter case
Lhe dark, pit-1ike deformity caused by a partial evulsion
may simulate an optic pit (I'igure 8.10A). 1 Visual loss
from these in juries is usually gre.it. Over a period of weeks
or monlhs, fibroglial proliferation obliterates the cavity
caused by the evulsion (Figure S. КЮ ).
A penetrating injury of the optic nerve bead may simu­
late a partial evulsion (I'igure 8. Ш1).
O C U L A R D E C O M P R E S S IO N
R E T IN O P A T H Y ________________________
Some patients following glaucoma surgery will develop
superficial and deep retinal hemorrhages as a result of the
pressure lowering - (Figure S. 10] and I.). Most often, even
though there is an increase in the retinal and choroidal
blood flow due to the sudden low intraocular pressure; ret­
inal bleeding is not seen. Elowever, if the increased blood
flow is excessive, autoregulation of retinal vesseEs cannot
tolerate the volume, which overwhelms the capacitance
of the capillary bed and retinal veins, resulting in retinal
bleeding. A sudden decrease in intraocular pressure also
induces forward shifting of the lamina cribrosa and acule
blockage of axonal transport. litis indirectly compresses
the central relinal vein and precipitates hemorrhagic reti­
nopathy resembling a retinal vein occlusion [Figure S. 10|
and
fl. It) E v u ls io n o f th e o p tic n e rv e h e a d .
A —D: l^rtial evulsion of the optic nerve head in a man w h o
suslai ned sudden loss o i v ision in I fie left eye during a b raw l.
H i5 visual acuity was 3/300. Therm was a large, jjjray,. optic
pil-Iike depression 'arrows-, A ' involving the temporal half of
the optic disc. rhene was ju'dapapiltary relinal and suhreLi-
ii.il I:i|г . Лi:;.:,i■Mj.r.iph'. xhiv.vi'd ; i 1.k i :iIi:шч1:ii:.iI ; r k r\
in [he area ot the partly evulsed optic disc (B and t_', steneoJ.
Eleven years later extensive libro^lial proliferation obscured
lhe optic nerve head from W ew i.L)).
E nnd F: Contusion necrosis and pari i л I evulsion ot" the infe­
rior half of the optic nerve head in лгт й-year-old boy imme­
diately alter the injury (E) and 4 months Eater ( f J.
G Hind H: Severe evt.lsion ol lhe o piic nerve head and contu­
sion necrosis o f the surrounding relina.
1: F’erforaling w ound ot" the eye simulating a partial evu l­
sion of the opiic nerve head in a 6-year-old hoy w ho was
hit in the eye wiLh a homemade saietv-piri dart iha) entered
the eye adjacent lo the inferior limbus, missed lhe lens., and
perforated 1he juslapapillary eye w all (arrow). The child
w ithdrew the darl him hell. B js visual acuiLy was ^Q/2ti0. Two
monLhs later he develofied cells, flare, and keratilic precipi­
ta les in the opposite tiye.
D e c o m p r e s s io n re tin o p a th y
j and К: Л JiQ-year-oJd on first posloperalive day wjth reli­
nal and pnerelinal hemorrhages followmji [rnlHJCuleclomy
with mitomycin С for elevated intraocular pressure second­
ary to herpetic trabeculitis (J], ALE hemorrhages resoEved in
2 months anti vision improved lo 20/40 with pinhole :К
L and M ; A 69-year-old hij;h myope Caucasian w om an
developed retinal and pnerelinal hemorrhages noted first
postoperative day follow ing trabeculectomy with mito­
m ycin С for primary open-angle glaucom a ft.. Her pne-
operalive intraocular pressure was 46mm and dropped lo
6 mm on day 1 postoperaLiveiy. She also had puripheral cho­
roidal deLadmicnls. O ptical coherence lomojjraphy shows
Increased refEectivily from the superficial foveal Eremorrhage
and shadowing posterior lo it (Mf. A ll relrnaE hemorrhages
resolved in 2 monlhs.
ij лг.-Л К, cuu rlus-y о Г 3>r. Kr.iucLh U n c h l i ; L ^iri(J M . L u u rlc sv ('I LJi i . к И н ч
kjmrrter. I
 Some of ihe hemorrhages itiay be white-centered. '['he
visual acuily is typically unaffected by these с Ь л о ^
unless a significant central retina I vein occlusion occurs."
IN T R A O C U L A R F O R E IG N B O D IE S
Л great variety of foreign bodies may penetrate the ocular
wall and become lodged wilh in the choroid and relina. [n
most instances Lheir idenUAy is known and measures for
removal are often undertaken promptly, [n some cases...
however, the invasion of the foreign body may nol be
recognized Lin til months or years later, when the patienL
experiences signs or symptoms related to breakdown of
Lhe foreign body (e.g., siderosis or chalcosis; Figure: S .]IB.
C. lr and j) or when a mass lesion in the fundus is dis­
covered on rouline eye examination (figure S.ILB-L).
Occasionally it may simulate a melanoma and resuEt in
removaE of the eye (figure JJ.llH - Ji].11-5-3,18, |Г,и Jhe use of
ultrasonography, radiography, and electroretinography in
mass lesions of uncertain etiology can reduce the chances
of this mistake {J:igure S .]IB ), lhe late development of
subretinal neovascularization occurring at a foreign-body
impact site may occur '' (see Chapter 9).
£U E Intraocular foreign bodies,
A: Metallic fipleign body lying on lbe inner retinal surface.
B: |u4bapapillдту piymenled tumur that was; suspected lo be
я melanoma. An tjrb-iC^I rtj^ptgehoyгзп^-, however, revealed a
meLallic foreign J>ody wiLhin lhe pigmented masii.
С—E: A juslapapillary pi^mcnled mass that was diagnosed as
.1 choroidal melanoma and lbe eye was enucleated. Gross
phq^dgraphs show thy mass Iлnows, Cl. H^btomicr-oafaphs
show the juxlapapillary mass that lies within the sclera and
choroid Ь еп Ш lhe atrophic геМпл (Dj. It stained positively
for iron Fira calcium, anti pdlarjiation (E) vev^ld evidencia
0I hemosiderin. These changes probably resulted from lhe
impact And subsoquenl distnlegr^lofi ot an unsuspected iron
(□reign body.
F-H: Intra(.jcuIiir iron foreign tiodv suslained while hammer­
ing on metal. Stereoscopic angiogram shows elevation at Lhe
silo of lhe embedded foreign body lhal was slil] presenl fol­
lowing .in atlempl Iо remove It afltN pare plana v il reclomy
and lensticlomy.
1 and |: (Ihalcos:s in ei 40-year-old schizophrenic man w h o
had visual acuity of 20/25, a mild sunflower cataract (]}, mild
^Iritis, dnd yello w mass in lh e иjperolem poral fluadi^m of
the lefl eye lj). There was no history of a foneign-body injury
and no sile of entry was found. O rbilal roenlgenugram
revealed a foreign body that proved lo be brass after removal
via 1he pars plana.
K --L, К ч п е ! Z iir im L T iiM n .' It f b .i, Л п i l t k ah M ' ' i l i : ■>' :iJ L ir i.
All n^hils генлимГ.
C H O R IO R E T IN O P A T H Y A N D
O P T IC N E U R O P A T H Y A S S O C IA T E D
W IT H R E T R O B U L B A R IN JE C T IO N S
Acute visual loss may be associated with retrobulbar local
anesthetic injections. ЧЪеге are a variety of mechanisms
causing visual loss. Ihese include penetraLlon of Lhe eye
wall, IS2"]SS penetration of the optic nerve, ]5SrlST^“ com­
pression of the optic nerve, intra-arterial injection of anes-
theslag and spasm of the central relink I artery (figure
S .]2). "" In cases of perforation of the eye the sile of exit
is often visible in the posterior pole and is associated with
variable amounts of intraretinal, subretinal, and vitreous
blood {Figure S. \2Л and IS}. Retinal detachment, vitreous
traction, and subretinal neovascularization may occur as
Eate complications {I’igure &. !2A-D). E’enetralion of the
optic nerve sheaths may be associated with intrasheath
injection, brains Lem anesthesia, respiratory a r r e s t , 10L'
and anterior extension of the anesLhetic into the subretinal
space.1 " Intrashealh infection as well as infection into
the optic [terve may cause occlusion of lhe cenlral retinal
arleiy and vein.1" 1161 or severe ischemic op Lie neuropa­
thy (Figure a.12Ji-L). Risk facLors include: sharp needles,
needles longer than 1.25 inches [3.17 cm),. axial myopia,
multiple injections, injections by nonophthalmologlsts,
enophtbalmos, previous scleral buckling procedure, tradi­
tional superonasal gaze position during the Infection, and
poor patient cooperation.1 Use of blunted retro­
bulbar needles 1.25 inches (3.17cm) or Less in length and
injection with the eye In the straight-ahead position may
be helpful in preventing visual loss.1 Ii3
Penetration of the anterior ocular coals during peri­
bulbar anesthetic Injections, particularly with sharp, small-
gauge needles, may occur and often is unassociated with
8. 12 Co nip Iic alio ns of retro bn Iba r ane sIh esia.
A —D: O c u la r perforation with a needle occurred during
Iосп I aneslliesia in Lhis- eldedv Woman sch edu led for catarafl:
e n a c tio n . i>he noled л dark violaceous spoL at l.he lime of
the relroE>ulbar infection rind pour сил Ira I vision pqstflpera-
Livojy. Three weeks Iл lei her via ил I acuity in Lhe I el I eye was
20'300. There was лп enl ranсe sile inferiorly and лп esiL Kite
jusl superior to Lhe center of (he гласи Id |arrows, A and Bf.
Ten months laLer her visual acuity in Ih e right eye was 5/200.
There was evidence pf nubrtilinal nyovascjlarizaLion sur­
rounding lhe езд sile (C and L>j.
E and F: Com bined central reLina! artery and cenlral relinal
vein o c c a s io n Was presen L on lhe lirsl day л Пет cataract sur­
gery under locnl nneslhesja.
G and H: This patienl noled marked visual loss on Lhe firsl
pu-.loperHlive day лПет calaracl ojilraclion done several
monLhs before ibete p holographs were taken. K o la рлИог
[)t lhe oplic disc and narrowing лnd cuffing ol Lhe interior
branch relinal arteries. Angiography revealed a large interior
zone ot" capillary nonporfus-ion (fHi.
I: Subretinal And inlraviCreal depu-prednisolone to I lowing л
scleral buckling procedure.
I — L: This hypertensive wom an noted loss of vision in this
eye during the course ol cataract extraction. O n the first
postoperative day her visuaF acuity was li^hl perception only
and the fundus showed a picture simulating I'UMschar's reLr-
tiopathy. rbe visual function gradually improved and several
monLhs Jaler her vibLial acuity wns JjWattJ. There was mild
oplic alrophy ■! and K)_ H ealed lasur scars aroim d Lbe site of
perforation ii).
permanent visual loss.:5- The author has seen one patient
who susiaiLted immediate loss of vision associated with
subreLlna! injection of Xylocalne and epinephrine local
anesthetic (see ]:igure 9J4L-J.J
P H O T IC M A C U L O P A T H Y
light may cause damage Lo retinal tissues by means of
three basic mechanisms: photochemical, pholocoagu-
lative, and mechanical. []hotochemical damage
occurs when light of the visible spectrum.. particularly
the blue end, causes photochemical changes and retinal
injury without significantly raising lhe tissue tempera­
ture. J^hotocoagulation occurs when light generates a tem­
perature of more than I0 °b above body temperature and
causes coagulation of retinal proteins. Mechanical injury
is caused by acoustic waves or gaseous formation afler
rapid tissue absorption of light. Many factors, including
pigmentation, clarity and nature of the media. WanrtdprigLft
of light, dose rate, and body temperature, a re important in
determining lhe nature of lhe injury
Solar Retinopathy
']he terms "solar retinopathy,D "eclipse bums," and "foveo-
macuiar retinitis,” which most authors believe aFe synony­
mous, refer lo a specific foveolar lesion that occurs: ( I )
in certain palients following viewing of an eclipse1" ! ■;
12] after direct sun gazing by lookouts,1' ' sunbathers,' ' 1
malingerers,' '■1,6 or schizophrenics1' (J5J as part of a
religious ritual"^'3' 4; (4] in young people under the influ­
ence of hallucinogenic agents, particularly i.SL> [Figures
S.J3 and fl.J4 )l:iU' r '-: and (5} in patients, typically chil­
dren or young adults, who deny a history of unusual expo­
sure to sijtfi. Those who admit lo sun gazing often
develop, soon after exposure, a central scotoma, chronia-
topsia. meta morph ops ia, and headache. The visual acuily
is reduced to 20/40 to 20/70. In most cases visual acuily
returns lo between 20/20 and 20/40 within a period of
3-6 months.1 1
During the first few days afler exposure a small yellow-
white spot wilh a surrounding faint gray zone develops in
the center of the foveolar area (Hgure tf.l3Aj. This spot
fades after several days and is replaced by a reddish spot
with a pigmenL halo. After approximately 10-14 days this
oflen fades from view and is usually replaced by a small
(25-50|jm), reddish, sharply circumscribed, oflen irregu-
Early shaped, faeeLed Lime 11аг hole or depression in the
foveolar area (I'igure S. 13B—J:). I his defect may lie imme­
diately beneath or just adjacent to the foveal reflex that is
typically present. It is not associated with an overlying
operculum or evidence of posterior vitreous separation.
Occasionally the diameter of this pit may be ]00-200|im
(I'igure 8 J 3 E and F ). Ihis pit is probably caused by focal
8. 13 Solar maculopathy.
A-D: l b is lfr-year-nld boy n o te d b lu rre d v is io n in bcitfi
eyefi H )o n At'ter h a v in g fjaz e d at the sun. W h e n seeh in it ia lly
bis v is u a l A c u ity w a s 2 W i0 in the ri^ h l e y e And 20^100 in
lh e lefl e y e . H o bad а ыпа1 I y e lle w spel in the fo veal t e n ­
ter Ol" b o th eyes 'A j. H u o r e s t e in a n g io g ra p h y w a s flOrmafci
T h irte en w e e k s laler, v is u a l A c u ity w a s 2O /20 in the rii^hl e y e
an d 20/ \0 0 in lh e let! e y e . In lb e t e f lt e r et b o lb f o v e is ih e re
wah a s h a rp ly c iT c u m s trib e d in n er ]д т е П а г h o le IB And C .
I w e m o n th s later lb e pi Is h a d e n la rg e d n lig h lly d J ) a n d Гh ey
re m a in e d u n c h a n g e d 7 year:, Lite r w h e n b is v is u a l A c u ity
was- 2 0/1 5 rn I b e righl e y e a n d 2 D/20 in I h e left e y e .
E ;and F: Lar^e foveoUr pi Is many years After sun £ja.zin.L;. The
paLierU's visual atu ilv was 2Q/30.
G —|: A 20-year-old m an with bipolar disorder on an tipsy-
t holies. Visual acuity was 2Л'30 in eath eye. Kolh macula
hhuw central yellow change and H i w ilh corresponding
pholoruceplof disruption on optical coherence Еопч)^глрЬу
f! and | .
loss of the retinal receptors.|:ii |й О СП' is invaluable
in demonstrating the focal loss of phoLoreceptors with?
sharply circumscribed edges (figure 8.131 and ]. 8. I4C and
H). It is permanent and is highly suggestive of previous sun
gazing. Similar lesions, however, may occur after sponta­
neous vitreous separation, usually in palienls 50 years or
older (see discussion of macular holes, Chapter 7), and in
si) me patients after whiplash-tike injuries (see figure S.05
Jl, p. 7 2 2 ).^
Jn some palients sustaining prolonged or repeated
exposures, particularly those under the influence of hallu­
cinogenic agents, a larger lesion with mottling of the RI1!:
may occur (Figure 8 .13A}.11''- lriL| Possible factors predis­
posing lo macular damage from the sun include younger
age (lens clearer), pupil dilation, relative emmetropia.
high body temperature, and geophysical conditions allow­
ing increase in the atmospheric transmission of ultraviolet
И radial ion to the barth's surface.
fluorescein angiography in most patients shows no
abnormality during either the early or the late phases of
the disease. In a few patients seen within the first 48 hours,
a small focal area of staining may be present. Days lo
weeks later there may be a small spot of hyperfluorescence
caused by a window defect in the BPE. '['lie presence of
Kanthophyll pigment in the foveal area may be responsible
for the difficulty in demonstrating angiographic evidence
of minor JtE4i damage in these cases.
 There is experimental evidence to suggest that the blue
wavelengths оГ light are chiefly responsible Гог produc­
ing l1 photochemical injury thal during Lhe fir^l 48 hours
manifests itsetf primarily as damage to lhe apical melano-
somes of the RJ’L followed by macrophage phagocytosis
of the meEanosomes in the subretina] space. Between 48
houre and 5 days after exposurer disruption of the recep-
Lor elements becomes more apparent. Much of this dam­
age is reversible and thus explains why many patients
regain good acuity1'" 14 In severe cases, depigmenlation
of the RPK and permanent loss of the receptor elements
may occur (Figure &. 34K and L). " Ihere is also evidence
to suggest that there is great individual variation in sus­
ceptibility for developing solar retinopathy. Some patients
with minima] exposure lo the sun [e.g., during sunbath­
ing) may develop a macular Lesion,1,11 1 whereas others.,
even after purposely staring al the sun for as long as an
hour may develop only a minimal lesion.' 11 Most patients
recover normal or nearly normal acuityr and no treatment
has been proved to be о Г value.
It is probable that acute visual loss in naval personnel
attributed to foveomacular retinitis was caused primarily
by sun gazing.j. it is atso probable that some reported
cases of idiopathic foveolar lesions, identical lo solar mac-
Lilopalhy, occurred in patients who for a variety of reasons
may have denied sun gazing.■ lh e possibility still exists.,
however, that there are other as yet unidentified causes for
this clinical picture.
S. 14 Probable solar burn.
A - H : rh i-s 42-yea r-ol rl F-EJI detec live com plained o f gradual
onsel t>f para cenlral small scoloinas о I 1-2 у elate' dura­
tion ir both eyes. Visual acuity w a s 20/25 in each eye.
Foveal 1binning 1ou lei lam ulkr hole! is noLud [л e k b eve
Dl appro* iт а Lely 10D-|im size lA and BJ. The foveal defects
are more discernibl-e on (he rediree photographs 1C and Dj.
Fluorescein angiography revealed no corresponding defects.
O ptical fibhefSnce tomojjfaphy done I year laler shove's
focal Iuse- of foveal photoreceptors corresponding lo Lhe
red lesions in each -eye It i and H). Visoal acuity and fun-
du i appearance have remained unchanged over 3 уггагн. He
denied sun ^aziny.
ClinFcopathologic correlation of a probable solar
macular burn,
J-L: A. 20-year-old Air RMte-enlisted man with л 2-week his­
tory of blurred vision in the right eye and a 1-week history of
blurred vision in Lhe left eye. He admitted being under [he
influence of L i l ? bul denied sun gazing. Visual acuily in the
right eye was 20/200 and in Lhe l-nc't eve was 2Q/60. In iheri^hl
eye Ьч." had a l^rge oval area of retinal bifjmenL epi I helium
iRH'tI derangcmenl centered in lhe macuia (I), In lhe left ffiac-
ula lie K id а Hmali yellow lesion singular lo Ihe one in :he r i p
иуч!. Fluorescein a n g io ^ a p K showed evidence of a w indow
defect in iheHI'fc in IЬг* riцЬI macula (Jl. Il showed no abrtor-
inalilv in Lhn lefl eye. Seven days laler lhe visual acuiLy in Lhe
tefteye had improved lo 20/30. Approximately 6 months later
he was killed in an aulomobile raccjdenL, rand his ву-и were
obtained a I autopsy. Hislopatholo^ic examination of Ihe eve
depicted in A showed focal loss of the rod and cone nuclei
and receplor eleinenls in the cenlral macular area iarrows, K..
Инзго was focal Ibinning arid depi^menLalior* of Lhe oLhenvine
viable R PE cells En (he foveal region I L.I. Arrow indicaLes the
junci ion between lhe normal and depi^mer>led KPL. K'ole
lhal Bruch'H membrane, ibu choriocapiilari?-, and lhe remain­
ing choroidal vessels are normal. Serial sections of the left eye
failed to reveal a definile abnormality in the foveal area.
Welding-Arc Maculopathy
lixposure to a welding arc commonly causes keratocon­
junctivitis, but only rarely does il cause visual loss. In
certain instances, however, (here ii some evidence lhal
prolonged exposure over j period of minutes or more
may cause facial burn, decreased pupillary response to
tight decreased acuily wilh a cenlral scotoma, j concen-
Lric peripheral field loss* and bio microscopic changes in
the macula Lhal appear almost identical to those seen fol­
lowing exposure lo the sun (Figure a.].5A-D).l!,4'],Jt-1':"1
Depending on the severily of the disease, visual acuily
usually returns lo normal in a in atier of days or weeks.
Jhe course of visual recovery and fundus changes closely
parallels solar maculopalhy. As in lhe case of solar macu-
lopathv, there is evidence to suggest that the retinal dam­
age secondary lo a weIditig arc is probably explained on a
photochemical ralher than a thermal basis and is primar­
ily caused, by the wavelengths at lhe blue end of lhe vis­
ible spectrum.Л|и Similar photochemical macular burns
may occur afler brief exposure to Lhe flash associated with
shorl-ctrcuELing a high-tension eleclric current (i'igure
ft.]5h-IL).'ni Dolphin and Lincoft'reported homonymous.,
oval, white relinal lesions in a patient exposed to a 700-V
eleclric discharge that occurred when m o electric rails gen­
erated an arc of Eight.-"■:-
In case of metal-arc inert gas (M iG ) welding, the arc Is
enshealhed in a stream of inert gas to prevent oxidation of
molten metal. The gas changes the emitted radialion into
the visible and. near-infrared range and can be absorbed
by the relina. resulting in thermal and photochemical
damage [Figure 3his is in contrast to electrical
welding arc where lhe radiation is predominantly in the
ultraviolet range.JiH,-!5;
Unusual fundus lesions reported in two patients
exposed let eleclric arc welding appear to be unrelated RPli
detachments in one patient and nonspecific chorioretinal
Scars in the ijipttr.205'2^ Jbere is one report of a macular
hole occurring after exposure to eleclric welding ire.2'07
fi.l"- P h o tic m a c u lo p a lh y .
A—D: Photic maculopathy caused by w e td irg in this- 19-year-
CHd man w ho developed marked pain in lhe eyes and pro­
gressive visual lots soon after spending 2 hours ■'tacking"
with a helium welder 2 weeks before his initial examination
л I the Bascom Fulmer Eye Institute. He had symmetric, small.
yeHow, foveolar lesions a l Ihe level of the retinal pi^mtml
epithelium KIHbl (A and hSj. J lis visual acuity in lhe ri^hl eve
was 20/[00 and in 1+icj lefl nytf was 2M200. Angiography ir>
b(rth eyes showed a small focal w in d o w d c fe d in the KF’t
derlfstty (C). Ten m m thb later lhe patients visual acuity
had relurned in lhe li^hl eve1 Co 20/30+ and in lhe lefl eye
lo 20/50 + . S o te Ihe slight enlargement of ihe area of depij;-
mentaLion in lhe center of the m-iicular .area itJl.
L - H: lfh iitic n '..H i иlopathy and lacial burns caused bv elec­
tric arc llash occurred in I his workm an iL< when he drove
a sp ite into a hi^h-volta^e line. Forly-ei^h! hours aMer lhe
injury, his visual acuilv in the left eye Was 20/50. I-Ее hail a
yeHow spjoL in the cenler o f Lhe fovua :Fl. Two weeks after
injury his acuity was 20/40 and lhe spot was less prominenl
Кг', ti^ht months after injury his visual acuity was 2&20.
There was в circular zone of dcpi |^jn en Lai ion ol lhe Fil'E H
that was readily apparent as a ring o f hyperfIuorescence
an^iogjaphically.
W e ld in g a rc n ia c u lo p a th y in m e ta l- a rc in e rt gas (MIC)
w e ld e r s .
I—M: A ? 6-year-olrl Caucasian w elder com plained of pl>o-
Lofisias and centTal scolom a for 5 days in His riyhl eye fol­
lowing an arc w elding flash w hile usin^ a .VlltJ. His vision
was 20/30 ::i the righl and 2Q/20 in Lhe lefl eye. Fundus
showed foveal delactimeiHs in holh eve1? И arid Jl confirmed
on optical coherence Lom ova pfift L and Ml. Huorescein
an^iogjam showed no leakage into Ihe subreLinal space
IК j. Observation was recommended: his vision improved lo
20/25 aL fi weeks and 20/20 al 6 months w ilh resokHion of
Lhe serous retinal ddachm enL.
IL M, i rum C lftfn t? r'l jl..'' 11-М, с ULirU'i-y <.?( Ur. Anyy Nrrfflnj.J
Lightning an d i Electrocution Retinopathy
lightning,, wilh a force of up lo \ million V and 30 000 A,
causes significant mortality and morbidity lo those in its
path. Lightning reaches its viclim by four routes: ( I ) direct
strike; (2J side flash - lightning strikes а nearby object
and arcs through the path of least resistance; (3) ground
current - lightning strikes the ground and trawls along its
surface; and (4) rarely, by current traveling through wibKt
or pipes reaching people in balli tubs or on the phone.
Ophthalmic injury from lightning has three proposed
mechanisms.2 0 4 The electrical current passes through
ocutar tissues, causing disruption of celE membraneSr con­
verts lo heal causing damage- and vasoconstricts causing
tissue ischemia. Industrial accidents or occupational inju­
ries from high-voltage electricity cause similar effects.210-215
]Ъе cardiovascular and nervous systems offer paths of
Lesser resistance and thus are more susceptible, though any
organ system can be affected.
Lightning-induced ocular injuries include thermal kera­
topathy, uveitis, hyphema, anterior and posterior suhcap-
sular cataract, and dislocated lens in the anterior segment.
Poslerior-segment injuries include vitreous hemorrhage,
retinal edema, maculopalhy. macular cyst (figure 3.16),
macular hole, cenlral relinal vein occlusion, central retinal
artery occlusion, thermal papillitis, and optic neuropathy,
lhe foveal changes seem lo result from dissolution of reti­
nal photoreceptors and adjacent neuritis (figure 8.1 6Gr H,
J, and L). Multiple cranial nerve palsies and nystagmus can
also occur.- "
Coming in contact wilh, or in close proximity to,
a high-vottage electric current results in acute visual
loss associated wilh macular changes.J0!::-jll" ,2ir,"-J -1
Jj. lt Lightning macuIopathy.
A -L: rhis 4^-year-okl fe r tile lott consciousness after being
struck by liyhtning w hile jo j^ in y. She awoke 4 days later
firrd com plainer! of decreased vision and hearing and suf­
fered burns 1o lier leM side and leg. Her vision w ilh pinhoJe
was 2CV70- and 20/50 + in I be Ш й eyes. She had bilateral
cenlral scotoma on lh e Amsler grid. The righL love о Ia showed
fi ye I low- isb change and lhe left eye a vitreous opacity and
reddish appearance Eo the loveola lA-DJ. There were dark
nonfEuorescenl dots in the fovea of EioLh eyes on the angio­
gram ■;!: and Fl. O ptical cohEirence tomography iO CT) of righl
eye showed increased density of the yello w lesion and the
phbtoreceptcirs ytiderrBath i1 and small cystic spaces oulside
the Foveola 1G1. The left eye O C T showed a cystic space IH
lh e vision in the right eye dropped lo 20/100 and lhe yello w
lesion Lurnod more diffuse and granular The t X I l now
showed dissolution o f the foveolar cells and receptors and
the residual ;n1emal I imi Ling membrane brid^in^ lhe space
(3). The left eye maintained 2tV50 visuaT acuity and die fovea
showed a tb rtracted ye Ikm1change lo its surface with under­
lying empty cavities let! cjver from Iojs o1 cells К and I Л
(A-L, (.riurlL'iy :•! jJr. Lj.i'.'iiJ I-int.i к '
MacuEar edenini simulating lierlin's edema seen early
may be replaced by lesions described as a "cyst" (E-'igure
S. 16], |macular hole," or solar maculopathy over time.
Eventually the macula is noted to be thin on ОСГ; a macu­
lar hole may spontaneously close or persist. UilTuse retinal
thinning and necrosis can result in atrophic relinal leans
and retinal detachment (figure Й. 17). Optic nerve pal­
lor and diffusely constricted vessels are noted in severely
affected eyes (I'igure £.17 C, L>, G, and 11).
 1^4, О
746 iL H A P T E R g
Acute Retinal Damage Caused by
Ophthalmic: Instruments
Jhe toxic effects of light on lhe retina in experimental ani­
mals have been documented in tlie сам cif the indirect
o p h th a lm o s c o p e ,in tra o c u la r fiberoptic
and lhe operating microscope.-1'14-2-1*' Lhe visible and infra­
red wavelengths of light are probably mast important in
:'.ui4 ::^ LnsLi'L'.n’.L'Jil-iiuhK'L'd i4-l:n.il L.i'sions
similar to those produced experimentally in animals using
the operating microscope and corneal contact lens have
been observed in humans fallowing exlracapsular cata­
ract extraction with and without intraocular Lens implan­
tation.2-17-2 17 On lhe first and second postoperative days
Lbese palienls may have a paracentral scotoma associated
with an irregularly oval, yellow-white, deep relinal lesion
that is mosl frequently located just above, below, or tem­
poral lo lhe cenLer of lhe fovea (E'igure fl.JtfA). [because
of the frequent use of a brid!e slay suture superiorly ihe
lesion has been reported mosl often jusl below (hecenler
of the macula. Lhe Eesion stains intensely with fluores­
cein [Figure 3.1SK). Jhis is replaced over several days and
weeks by a zone of fine mottling of lhe RPE (l-igure 8.1 SC)
that is most easily visualized as a Focal area of hyperfluo­
rescence angiographically. One case, reported as an exam­
ple of "pseudophakic serous maculopathy," was probably
alsocausedby phototoxicity.-"- Although in most patients
central visual acuily is unaffected, lhe scotoma may be per­
m anent/'■: i "'1The retinal xanlhophyll may play a role in
ameliorating the effects of iighl damage to the center of
the m anilia^^237 Jlie reported incidence of pholic in acu-
lopalhy following exlracapsular cataract extraction var­
ies from 7 lo 2ф%.11Я'2И The most significant risk factor
is lhe perioperative exposure lime lo the operating micro­
scope light.24'* A variety of measures may prove effective
in reducing chances of pholic maculopathy in humans,
including reduction of operating lime- frequent cover­
ing of lhe cornea, oblique illumination, ultraviolet fillers,
utilization of an air bubble in Lhe anlerior chamber, and
insertion of the intraocular lens wilh lhe piano surFace for­
ward. Jletinal burns, however, have occurred in spile of
all of ihese precautions, excepL the last mentioned.-'
Retinal lesions identical to those produced experi­
mentally with endoilluminalore have occurred during
the course of pars plana vitrectomy in humans.--^-'1- 'L'
Jypically the burns are sharply defined, less than two disc
diameters in size, and assume the shape of the light source
used: oval if by filament and round if by fiberoptic. Larger
more pleomorphic burns, however, may occur. The great­
est risk appears lo occur during surgical removal of epireli­
nal membranes and conical v i l r e o u s . Reduction of
Lime of exposure, use of low-power source, and avoidance
of blue light and high temperature of infusion media are
recommended to reduce the risk of a retinal burn/"'1i.ight
damage to the reLina may occur in the detached as well as
the attached relina.1,1,1
B.17 Electrocution relinopalhy.
A—J: This -11 -year-old w indow installer East consciousness
,ir>d fell following electrocution w ilh з live wire. His visual I
rituily w-ias 20/200 in- lhe? rij’hl eye and ^/200 in lh e lefl eye.
He f.romplнin-L'cl of ipecrBasfed color vision nnd mild aiSisacCH
ria. ВЫ Ei lenses showed symmelricfil steEEaL-e calaracts. Two
weeks after onset, lhe fundus showed pallor ot lhe optic
disc and с Ы ton-wool spots inferior Lo Ihe disc bilaterally
(C and D). Angiogram showed foveal thinning on the right
and otLlus-ion of н11*.1 11 vessels corresponding to Lhe nerve
fiber infant Is :L: and I-). Three months idler onsel. the collon-
wool spoLs had resolved Id and H). The o plic disc con Li n-
ued to 1>е pale. He develojfed a relinal delachm enl in the
Feft eve requiring a viLrectonry and a buckle. His CoEdmann
visual held showed residuaL interior fields in the left eye
а иd a nasal held only in Ihe rijjhl eye. Hum phrey visual
field showed biEateral nasal field defecL. O ptical coher­
ence tomography ai 1 year showed symmetrical severe reLi-
rigj thinning w ilh progressive cataract in both eyes IE and JJ.
His right eye improved lo 20/70. The left eye remained at
20/200. Further hislory revealed he was cherry picking and
moved inlo a high-lensfon line, receiving 1 000V electrocu­
tion Lo lhe shoulder.
lA-J, c i i u r l u L y Ml Ur. M i h .m l tloklb.iLnn.-
Jftslopatbologic findings in animals and humans
exposed lo lhe operating microscope have shown evidence
of photoreceptor and RPE damage in the area of the visible
retina] burn. " " '-11 '" Animal models have deEnonslraled
that high oxygen tension in the bk>od is associated wilh
worsening of light damage lo the relina*1 high levels of
serum vitamin C, corticosteroids, and dimeLhyllhiourea
exert a protective effect.■',!ч ~ы-' Mitochondria are particu­
larly susceptible to light damage, perhaps because they
contain cytochromes that absorb the light.:il
Although die operating microscope light has been sug­
gested as a possible cause for clinically significant cysloid
macular edemar there is little evidence to support this
idea
Retinal Injury from Laser Exposure
Accidental pholocoagulation hums wilh ruby, argon.
neodymium-YAC, and rhodamine dye lasers, femtosec­
ond laser have been reported." J Hortunately, in
mosl cases good visual function has been relained. Figure
S.13D-K illustrates how a moderately intense solitary
laser burn to the cenLer of the fovea is compatible wilh
return of good acuily in spile of destruction of the central
pholoreceptors.
Ophthalmologists who use operating microscopes
or who do laser pholocoagulalion may have decreased
color discrimination for colors in a liitan color confu­
sion axis.*1''’'- ' ' ■ ''Jhere is a correlation between the years
of laser use and the chronic reducLion in color contrast
sensitivity.
 W ilbers et лL. reported four patients with bilateral high-
grade carotid artery stenosis who experienced episodic
visual impairment retried exclusively to light exposure:"77
ihey postulated that this may be- related lo delay in regen­
eration of visual pigments caused hy ischemia.
Accidental macular injury from YAt. laser disruption of
sub hyaloid hemorrhage can occur due to the photodisrup-
tive effect of the YAC laser. A macular hole or cyst is seen
due to loss and dissolution of tissue (t'sgure fl. ISG -Lj.The
macular holes can spontaneously close or remain open.
Secondary choroidal neovascularization can occur due to
breaks in the Bruch's membrane Visual prognosis after
closure of the macular hole is variable and depends on
collateral damage Lo adjacenL cells and tissue.J ' '
Laser Pointers
l?ed laser pointers are safer than green laser pointers.
RoberLson el al. evaluated clinically and histopathologi­
cally effects on three eyes wilh red laser pointers and one
wilh green laser pointer.'1' 4-'4 Salients with melanoma
scheduled to undergo enucleation were exposed to the
laser pointers for 1 minute with foveola fixation, S min­
utes Ье1ог^ fixation, ,md 15 minutes above fixation, lhe
eyes exposed lo red laser pointers sEiowed no clinically or
angiographically discernible changes, ihe eye exposed to
green laser showed a yellow change at the level of the RPH
at ] -minute exposure in lhe foveal center, and 15 min­
utes superior lo the fovea. ОСГ shewed thickening at the
level of the RPE at 24 hours al bolh Locations. J iistological
examination 20 days after laser exposure showed focal
clumping of pigment granules and apical movement
of nuclei in some [£PL cells. There was some displace­
ment of RPh cells into the subretinal space with minimal
changes in the overlying photoreceptors and none in the
choriocapiHaris. In spile of Lhese histological changes the
patient was asymptomatic. Jhe eye lhal received red laser
exposure showed no such change. Overall, transient expo­
sure to laser pointers, either green or red with the normal
blink response, evokes minimal risk..J,',,’i■-■'0 3Lowever chil­
dren should be warned against playing with laser point­
ers inhere they may stare at the laser light for a prolonged
period.
Retinal Damage Caused by Chronic
Exposure to Sunlight
The effect of long-term exposure to ambient light on the
retina is the subject of considerable controversy. Ihere is
some evidence to suggest that age-reEated macular degen­
eration may he aggravated by tbe amount of exposure to
Lhe visible wavelengths of sunlight but not to ultraviolet
hghi.Jfl0-J^
S.I P h o l ic m a c u lo p a lh y fro in m icro s c o pe 1igh I.
Л -C: O n e day йЙег ехрСйШе [jf Ihe ri^hL m acula of л pha3ci£
c*ve to lhe opefeUng m icfoscope for а puriod of 1 hour. The
eye Wap blind because of a craniopharyngioma. Note Lhe
дгау-whiLe lesion localutl л1 thu IqWel ol Lhe relinal piemen I
epithelium I hi H"E1 (A) and Lhe intense fluorescein staining of
lhe outer relina !Ё\ t.L^hl days а Инг lhe exposure there w h s
moLlling of Ihe KfJ E ii> the area of lhe lesion Ю .
D -F: Acule ruby laser burn in Ihe center of Иге fovea of a
man with a ciliary body melanoma. Visual acuily before Lhe
bum was 20/20 and the fundus was normal |DJ. Five minuLes
aflur а т<х!итл1е1у irilense one-decree burn IЬя I generated л
small steam bubble, lhe™ was л Central yray loveal opacity
1!=:. Пне visual acuity was 20/70. Twu weeks la Lei Ihe acuity
bad returned lo 2CV25 al Lhe time* ot enucleation. i^irLlal
destruction o f lhe central foveal area.
Laser in d u c e d fo veal b u rm
G —L A 42-yeai-oltl man was i-een with co m pi a inLs of
decreased vision in his rijjht eye oF 1 m onths duration. He
haii suffered л vitreous hemorrhage following head injury
2 months previously. On recovering tonscicaiflSeBi, 1h-E1 treat­
ing ophlhalmologisL performed laser pbotocoaguiation o f Llie
posterior hyaloid for premacular homorrhatje. O n examina­
tion;,, hiн best-corrected visual acuity was 2<У200. FundoscDpy
of the right eye (C ) showed a cenlral m acular hole (arrow­
head I with flemajpafldn lines ex lending temporally (arrows).
The hole was bmier appreciated on optical coherence lomojj-
raphy imaging (HJ. fluorescein angiography 11 and J} showed
transmission hvperfluorescence in Lhe center larrtjwhead'
w ilh prominent dema real ion iinet lajraw sk Raster line аслг>
fK 1 [Kissing through the foveal cenler showed e leva Led inler-
nal limiting membrane {ILM ) I arrows j corresponding lo Lhe
dema real ion i in r_«5- seen temporally, indiciJlinu; Lltwi I lh e pa Lien I
mijjht have bad ТегмгЛ syndrome following head injury, [he
foveal cenler shows an outer m atular hole (arrowheadI lhal
mosL likely resulted from lhe laser disiuplion attempted by
the beating physician Lo drain sub-1 LVl blood. O verlay RPt-fli
scan iLl shows the hole.
! Л —С .. I t t m t i k iib L 'r lK L ir i .h m l I t i l d n i . i n - " 1 | n i i : l ч-5-j.-tl w i L h p e r m : м ш п
from !h t А п н тк '.т Jriurn.il ul Оди^,з1тЫйв.у; l tj^YTlghl IJphlh.iJrok
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Specific Circumstances Resulting in
Chorioretinal Trauma
■ Recreational: firework.- paint ballr fishing hook and lou­
vre. golf club and golf ball (more often club Lban ball).,
baseball, sofl ball, hockey puck., basketball, БВ gun
pellet
* Occupational: intraocular foreign body, explosives,
improvised explosive devices, war injuries, blast injury,
electrical/welding arc
■ Domestic: bungee cord, air bag. pencil, scissorsr dog
biles
■ Homicidal: gunshot, knife, bottle, fist.
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Toxic Diseases Affecting the Pigment
Epithelium and Retina
Medications or olher substances lhat find their Way into
the eye may cause visual dysfunction by virtue of a toxic
effect on Lhe sensory relina. the relinal pigment epithe­
lium [RPh). and Lhe opllc nerve. In some instances [e.g.,
digital Lis toxicity) visual symptoms may be unassocialed
wrtb ophthalmoscopic changes in the fundus. In other
instances lhe ophthalmoscopic changes may involve any
one or a combination of Lhe RPEr retina, and optic nerve
head. Muorescein angiography is particularly valuable in
detecting mi id Loxic alterations of the Rl’Ei before they are
apparent oph Lhal mosco pica Hy. Optical coherence tomog­
raphy [О С ]'), aulofluorescence imagings fulE-field, and
multifocal eleclrorelinograpliy help localize the defect in
tnany inslances.
C H L O R O Q U IN E (A R A LEN ) A N D
H Y D R O X Y C H L O R O Q U 1N E
{P L A Q U E N IL ) R E T IN O P A T H Y
Chloroquine initially was used as an antimalarial agent in
World War II, but since 1959 it has been used in the treat­
ment of amebiasis, rheumatoid arthritis, scleroderma,
and systemic lupus erythematosus. ] lydroxychlorocjuine
has largely replaced chloroquine due to lower incidence
of toxicity. Degeneration o f tbe Ri>l!. and sensory retina
caused by prolonged use of chloroquine or hydroxychlo­
roquine is one of the most important of the ret ino Loxic
diseases.1"2' Most patients who have developed retinopa-
Lby have received daily doses of chloroquine in excess of
250 mg or hydroxychloroquine in excess of 750mg for at
Eeast a total dejse of between ]00 and 300 g.J'' There is evi­
dence that the incidence of retinoloxic effecLs is lower fol­
lowing hydroxychloroquine than following chloroquine
lh e ta(^ ]&,J:L',i:3-:i:: 3:our unequivocal cases of hydroxychlo­
roquine retinopathy were reported prior to l9 9 l.Jv J"J I'
All had normal or reduced visual acuity, paracentral sco­
tomata, acid bull's-eye maculopathy. Some have evidence
of peripheral retinopathy.' : Although it has been sug­
gested that patients receiving daily dosages of hydroxy­
chloroquine up lo 400 mg or 6.5 mg/kg of body weight per
day may tolerate massive cumulative doses (for example
3lJ23g) without developing retinopathy.'" such did occur
in one patient who received 4Q0mg/day and a total dose
of less than 21)20 g."' ' -Gass has seen another woman who,
after lakittg a total of I46g [ZOOmg/day X 730 days] of
hydroxychloroquine, experienced rapid development of
paracentral visual field loss and early bull's-eye maculop-
alhy. lhe retinopathy caused by both dru^s is probably a
general toxic effect but some eyes have developed toxicity
after minimal exposure while others with long usage show
no ill effects. This implies that some eyes may be predis­
posed Lo toxicity sooner than others by unknown factors.
A study of eight patients with chloroquine ami hydroxy­
chloroquine retinopathy for AtfCAJ mutations revealed
two patients with heterozygous Л BCK missense mutations,
hut none in 30 controls, suggesting some patients with
9.01 Chlo roq иin e a nd hyd roxych Eoroqui ne
retinopathy,
A rind B: A/ber receiving chloroquine, 250 mg daiEy far
17 yt'iirH for discoid diSSemic^ted lupus erythem atosus
Lhis- "iO-year-old wom an noltid blurring o f vision in boJh
eyes. Visual acuity was 2CV30. She had a sym m fljic bull's-
L*ye pattern o f alrophv of Lhe retinal pigmEnt epithelium
iKE’bi in holh eyes Д). Елг1у а Н в г р м п о й ^ р К ^ й angi­
ography revealed evidence of preservation o f Lhe cho-
riocapilEans wrthin the area of RFE alrophiy centrally lB>.
Eleclrorelmo^raphic № d in № w ere normal.
С an-d 0 : This 53-year-old wom an received a lolal dose of
454 ^ hydroxychloroquine and ch I oroq ui no (sver а 3b-iv,onlb
period. Shy showed p[Mrfes5lve Rf’E and relink I degpne'r&tion
for 16 years after slopping Ihe medical ion.
E—H: This 50-ytiar-oEd wom an, w h o received chloroquine
5 00 nig/day for 13 vears for rheumatoid arlhrjtis, Erevan
Lo nolice a "h a lo " ncoLoma and nyclalopia in both eyes in
February 1977. Her visual acuity al [hat lim e was- 2U/30.
ih e bad a b u 11's-eye pattern of K I’E alrophy bilaterally IE:.
Her elocLroreliiTo^raphic findings wore потппа!. The cEiloro-
r]Liinu was disconlinued. 5ev6n yearn laler Lhe buil's-oye pal-
lorn o f aLrophy bad enlar^tid slighlly and he; visual acuity
had decreased Lo 20/50 (F and G ). Two years laler кhe had
experienced furl her Joss of vision. Tbe cenlral Islarfd of KF3t
showed lurLhei evidence of alrophy angiographic л Ily :H'.
Vjsual acuity aL that brne was 20/2CM).
1: l-tislopaLholo^v of chloroquine m^cljlDpathy showing local
foss o f Ihe outer nuclear Эауег and lh e receptor elements,
irregular dfflpi^m enialion of lh e hJFE, and pnesorvaLion of lbe
choriocapillaris.
J- L : Л 45-year-old wom an w ilh lupus since ago 4 shows
widespread photoreceptor and pigment epjth“ 3ial loss in
addition lo lh e biill's-ove chaftger ^ h ich fjro^resnc^ despite
cessation of chlorrjquine after more ihan 20 ^'ears o f use. Her
visual acuity was 2 0 /4 0 and 2£V5-0. An eEeLlroretinogram
shovi'ea moderate red uc I ion of rod and со л-j function.
I ( J .h m l IJ, l O L ir L t '^ \ u f 3> r K jy ■ ( j y . i k i '. V L i . '. v c r c m i n d s 'b y e j n e fte r
11| i>d .1 iii .1 [oг^.vv ; l J U ^ г f fj <:■г I by b - r in k 'L y H a t .- I, ! n j m '•VfL 'U i; r h i n h r i
All
.1 r , [ J W j n l t ' r " " t- Г 9 (1 ^ . A i f i L 'n L j n M L 'ili( .'l A is n c u it lu n . r i ^ h l . i n ' i L , r v i., :l
АБС?? mutations may be predisposed lo retinal toxicity."
Vitreous fluoropholomelry has demonstrated a breakdown
in the blood-relinal barrier in palients receiving chloro­
quine but not bydroxychloroqui ne.24 'lhe earliest sign o f
toxicity, which may occur before development of any o(her
ophthalmoscopic o r e!eclropbysiologic abnormality, is a
paracentral visual field loss. ]he patient's use of the Amsler
grid may be helpful in detecting these early field defects.'
'lbe earliest ophthalmoscopic and angiographic altera­
tions in the RPli occur in the parafoveal area [E'igure
9.0] Л-С anti Ii—К J . At this stage a paracentral scotoma and
minimal or no loss of visual acuity are characteristic. An
enlarging ring of atrophy of the J?ETEi surrounding the fovea
produces a bull's-eye-like lesion that is indistinguishable
oplnhaimoscopicaiLy from other causes of this lesion {see
Chapter 5). .-Vs the E iM alterations extend into lhe foveo­
lar area, the patient loses cenlral visioil. Weiler el al. have
suggested that the retinal xanthophyll in the foveolar area
may exert a photopnoteclive effect in lhe various causes of
bull's-eye maculopatby."1 '' In addition to changes in the
pcrtfiataf pole, continued use of the drug may cause exten­
sive alterations in the RPE and retina peripherally { figure
■>.011?.- J-E.J. Ihese changes, together with narrowing of the
relinal vessels and optic disc pallor, in ay resemble primary
tapetoretinal dystrophies. Severe visual loss and blind­
ness may eventually occur. Other ocular changes caused by
chloroquine include whitening of the lashes, a whor!-like1
pattern of subepithelia! comeal deposits, decreased cor­
neal sensitivity, and extraocular muscle palsies.
Kluorescein angiography and fundus autoiluorescence
imaging (I'igure 4.02 C-li, K, and L) are helpful in dem­
onstrating the I'aint bull's-eye pattens of hyperfluores­
cence before its detection biomicroscopically, particularly
in patients with blond fundi. In patients with darkly pig­
mented fundi, biomicroscopic evidence of RPE changes
may precede angiographic c h a n g e s .lh e area of ПРИ
depigmentation {I'igure 9.011V К H, and I) in general cor­
responds to lhe area of field loss. There is minimal angio­
graphic evidence of damage to the cboriocapiliaris in the
areas of RE’Ei depigmenlation [E'igure У.01К, C. J. and K)
(see discussion in Chapter 2) '['be detection of small para­
central scotomata to red light is one of the earliest findings
In chloroquine toxicity. Lise of static perimetry through
Lhe vertical meridian may be the most sensitive means of
detecting the early visual field damaged Multi fiscal elec-
troretinogram (ERG ) may be able to detect early drop in
receptor amplitudes in the parafoveolar region.,5D‘:3f' OCT
is often able Lo detect loss of photoreceptors before angio­
graphic changes (I igure £.02С and tl). Ihe electro-oculo­
gram (LO G ] may initially be supernormal [2GO-350%).''
Ideally patients requiring more than 200mg chloro­
quine or 350mg hydroxychloroquine daily should have a
baseline complete eye examination, including visual acu­
ity, visual fields, and fundus photography. Ef there is any
biomicroscopic evidence of abnormality of ihe Rl’H or
other signs of retinal degeneration or a family history of
retina] degeneration, fluorescein angiography, multifocal
9.02 Chloroquine retinopathy.
Л - H : This M-ycw-ofd А Г м с л п Am erican w im a rt w h s - treated
with chiuruquine for ID years aL a dose Ы 25-0 mjj once daiEy.
bhe hiid difficulty f<mttsing for Che раиЕ year EjliL could read
20/25 wiLh a correction c f —3.00 D. She ttxiild o r I у see Lhe
Lt?Ht plalle ort Ihe Isbihara t hart in each eye. F JIid tiS photo­
graphs hhcjvv a rin^-Hhiipfd retinal pigmenl epi I ht?l i uni ;КГ1'
nLnophy spajfi^ig [lie fovea] OSnter iA <md Hi, corresponding
decreased trij Гofl Laore silence IC And [Jl and w indow Defects
gn Lhe angiogram ■;L and Fl. G plicai coherence tomography
trf buLh еуеы shows disruplLon of photoreceptor^ and loss ol
inner нецгпогП/оиГег segment (rS-'O^' juncLinn in lhe fovea
(atitows) w:tli fMLc.ii v pres^ff Vnit itjit of rue [jpl ors in the Годезл!
eerier.
EKG, full-field EiEiG and EX3G should be considered as part
of Lhe base'ine workup.
in the first 5 years of chloroquine or hydroxychloro­
quine therapy the American AcadeLny of Ophthalmology
recommendations suggest exams at periods appropri­
ate for the patient's age. After 5 years of therapy annual
exam including centra! !0 n visual field optical coherence
tomography (О С Г), color vision, and dilated fundus exam
is recommended. However any suggestion of early field
defects, changes in color perception, and other degen­
erative changes al the ttFE/outer retina should warrant a
prompt evaluation with auto fluorescence, centra! visual
field testing, fluorescein angiography, and discontinuatioLi
of the drug. Al the present time, multifocal LRG may be
lhe most useful means lo delect early changes, even before
visual field and angiographic changes appear. 11 О С I'
can show toss of peri foveolar receptors much earlier than
discernible changes on fundus examinaLion or fluorescein
angiography. Most of all, attention should be paid to the
patient's symptoms - variously described as changes in
color perception, areas of their face missing when looking
into the mirror, or parts of th e'IV image missing, and dif­
ficulty wilh dark adaptation.
 hp4ppjtiioJoglcallyr depigmenLation оГ lhe ИРЕ, loss 9.01! Continued
of" lhe rod and cone receptor elements, and suhretinal I—N : A il 4-year-old Indian w om an received chloroquine
dumping of pigmenL occur in Lhe macular area (Figure lor 2 years. Rrjlh. Ппаига b v t an incomplete; bull's-eye
9.0! 1.)."л *' lileclron microscopic studies have revealed appearance il and I that aie mure visible and widespread
widespread changes in Lhe relina, with Lhe most severe en aulo fluorescence imaging IК Hind Ll. Л L .!■'.;Vмл 11
elecprelincrgrarB shows patchy pholorecuplor dysfunction
occurring in Lhe ganglion cells in spite of Lheir relatively
with reduced amplitudes in [he lovea in both eyes (M and Nf.
normal appearance by Eight microscopy." I here is exper­
imental evidence lhal chloroquine is concentrated in : I—N. cuuriL'iy ill D t. Vi stull ti-.:pl i ;ird I Jr. Amud (JupU..
the RPL and remains there long after cessation ol" treat­
ment. ' In experimental mice given inlraperitoneal
chloroquine, ihere was marked abnormality of the outer
retinal layers with complete loss of the ouler plexj form
Layer, photoreceptors, and photoreceptor nuclei. The RPB
demonstrated focal atrophy, loss of nuclei, and pigmenL
Irregular! Ly. lhe inner retina showed loss of Muller cells
anti the presence of" membranous cyloplasmic bodies. In
contrast, those experimental animals given the drug orally
have shown much less damage with most changes lim ­
ited to Lhe KPli and photoreceptors. Ihis suggests thal the
appearance of toxicity at variable durations of treatment
and at variable cumulative doses in some patients may
be related lo the difference in absorption and bioavali­
ability of the drug.''' Although there is some evidence lhat
Lhe early eleclrophyslologlc changes may be reversible, in
most cases, once visual loss has occurred, it is irreversible
and may progress long after cessation of treatment (Figure
9.Q1E-L].1],]4',M''J9 There may be an interval of 7 years or
Longer after cessation of chloroquine and lhe develop­
ment of the first signs of retinopathy.''" Some patients
with disease attributed lo Late onset and progression of
chloroquine retinopathy may in fact have had a geneti­
cally determined disease that can cause fundus changes
identical to chloroquine relint]pathy (e.g., cone dystrophy,
rod-cone dystrophy ceroid lipofuscinosis, and Stargardfs
disease].
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® OD N O S

T H IO R ID A Z IN E (M E L L A R IL )
R E T IN O P A T H Y
3\nients with acute thioridazine relinopalhy typically
experience blurred vision. dyschromatopsia (brownish
coloration}, or nyctalopia 3-Д weeks afler receiving the
drug in excess of 800mg/day'" 53 and less frequently in
lower doses.'" |:‘ Maximum daily dose seems more criti­
cal than cumulative dose. The fundus may be normal
initially. Iл ter a mild, fine, then coarse granular sall-and-
pepper pigmentary relinopalhy with a neb lively uniform
distribution involving the macula and sometimes the
midperiphery at well, may occur (ligure 9.0ПА). In Some
patienls this may progress to include patchy or nummu­
lar areas of toss of (he and choriocapi!laris {J-igure
IJ.O jiD -L)''"' 1,11 and may eventually progress to a severe
diffuse tapetoretinal degeneration. Progression of the pig­
mentary changes but not necessarily functional changes
may occur after lhe medication is discontinued.
Visual function may occasionally improve after cessation
of toxic levels of the drug. " Olher patients, however, may
experience a lale, slow progression of functional as well as
anatomic changes. 'Ihe progressive enlargement and con­
tinence of patches of exlrafoveal geographic alrophy of lhe
ЦРЕ and choriocapillaris are similar Lo those seen in gyrate
atrophy. Bieltfs crystalline dystrophy, and choroideremia.
I'luorescein angiography ntay be helpful in detecting mild
ЙРЕ alterations (l-'igure 9.03В and C). The ERG responses
may be normal early but become attenuated later in more
severe cases.
Mistopathologically, thioridazine retinopathy is asso­
ciated with atrophy and disorganization of the photo­
receptor outer segments followed by loss of lhe RP1L and
choriocapillaris '
Itelinoloxicily has been attribilled lo concentration of
the drug within melanin granules in the uveal melanocytes
*5.03 T h io rid a z in e (M e lla r il) retin o p ath y^
A -С: M ild visual icres occurred in a 21-yeif-cild wnm an w ilb
schizophrenia w h o received ih^uridazine, flOQmg/daft Гог i
years. The mild pigment epithelial alterations (A) w ere mure
apparenl anyiu£$rapbrLJilly i.li and C).
D - C : This 60-year-old w om an received thioridazine daily
Гог 1 I years beginning; a.t sge 2.1) year*. Sihe was asymptorn-
a Lie visually and had 2СкЙ0 visual acuily biJaLeraNy until aj^e
55, w hen she developed nyctalopia and paracentral SLoto-
mas. Her visual acLiily was 20/25, rii^hl eye, and 20/30, lefl
□ye. ih e had VvideJy Scattered areas gaQgfapht^ atrophy of
the reLinal pigm enl e p ilhelium !Rf3L. that included Ihe тл е u-
Iа г area ■
.D-H I.
G-L; This 48-year-otd wom an com plained o f progressive
cjcnslriction of her visual fields for yeara, mare prominent in
lhe past h monlbn. Нет vision was 2<Y40 O L J anti 20/80 O S.
4be had ieCe)VEd thioridazine for 2 years, w hich was discon­
tinued 15 years prior following development Ы retinal and
visual field change*;. She had nummular art’as of KPb loss in
bolh е у к Id , H, and Li progressing lo choroidal and relinal
vascular atien nation and optic atrophy U-K.l.
K J- L , clh j N c j s v n l l> r . M u h n t j l A J i . i w c il 'I . )
and RPE.'451 llie drug inhibits oxidative phosphoryla­
tion, resulting in abnormal rhodopsin synthesis, which
causes disintegration of rod outer segments/7, lhe К I’К is
overtaxed with accumulation of lipofusciu as abnormal
pigjnenl granules. In addition il is believed that thiorida­
zine and other phenothiazines block the l>4 dopamine
receptors with subsequent increase in retinal melatonin
synthesis and activity. 'Ihis occurs in the phoLoreceplors
and КГ}: where the D4 subtype of the D2-receplor fam­
ily is predominant."" Jhioridazine has a structure similar
to NL3-2Q7, an experimental drug that was never marketed
because of severe retinoloxicily/'' Ihere is no specific treat­
ment other than stopping the medication.
C H L O R P R O M A Z IN E (T H O R A Z IN E )
R E T IN O P A T H Y
Chlorpromazine rarely causes relinal loxicily. When taken
in large doses in die range of 2400 mg/day over 12 monlhs
tt may cause mild pigmentary changes in die re Linn (figure
D.04A and в }.5 ihese rarely are associated wtlli visual
or functional deficits. lieeau.se patients receiving chlor-
proma^ine have often received other medica Lions that may
have Included potentially retinotoxic drugs, assignment of
Lhe exael cause of the retinopathy may be difficult. W hile
and fellow-while granular deposits may occur in Lhe axial
part of lhe anterior sub capsular region of the lens, and
ill Lhe posterior layers df the cornea in patients receiv­
ing 300 mg/day of chlorproma^ine for 3 years or more. 9
lhe usual dosage- of chlorpromazine is 4(J-7!> mg/day,
although dosages up Lo BOO mg/day are nol uncommon.
C L O F A Z IM IN E R E T IN O P A T H Y
Clofazimine is a red iminopbenazine dye used concur­
rently with dapsone and rifampin as the treatment of
choice for lepromalous leprosy, for treatment of dapsone-
resistant leprosy, and for Myccbaclerium nvium complex
infections in patients wilh acquired immunodeficiency
syndrome [AIDS). After several monlhs of treatment, clo­
fazimine crystals may accumulate in the ocular tissues.
Reversible si de-effects include a superficial whorl pattern
of anlerlor corneal pigmented lines, brownish discolor­
ation of lhe conjunctiva and tears, and crystals in the iris
and sclera. A large bull's-eye pattern of pigmenl epithelial
atrophy (I'igure 9.04<J and D } has occurred in iwo patients
following 2CKJmg/day (total dose of approximately
4flg) and after 3Qt) mg/day (total dose o f approximately
45gj *it6a '['hjS associated with reduced ERG b-waves
and full-field photoplc and scolopic as well as flicker
amplitudes.
*hQ4 Chlo rp roma zin e and tri il uope razi ne ret ino palhyL
A—G: This 4 ] -year-old schizophrenic wom an received chlor-
promazine (Thorazine} and trifluoperazine (btelazine) fur
tnany years. There was no definite history of ^t^tm enl w ilh
i ii- и .I/ 'г:- I !■I \h-.i-: .:a !.v i l I 111 ч1
-: : ■ ■: ■ Sb
had diminished photopic and scolopic responses eEeclrafeLi-
nographically. rhe pnlchy and nummular л red к ol atrophy of
the relinal pij’m t'iil epUhcSiurn. ■ЬЗl-'LI innowh A and tt were
нiin i I г to those caused by Ibiotidazine Lox.rcily.
Clofazimine retinopathy,
С and \)\ Айег ft months of trealmenl with J 3 g clofazim ine
for ftf уCuba av/uni complex associated w ilh acquired
im m unodeficiency syndrom e (AID S), this palienL developed
fi bull's-eye pa 11urn □( K J'L moll led depiLjmenlatitm in Ihe
macula bilaterally. His visual acuiLy was 20/25. There was
ног™ generaIized reductjon of all co n p o n en ls of his eleclrn-
retinogram it К С ) jjpsponses. His ctHttr Vision (A O H R U pseudo-
isuchrofnalic plait's; was ПОЧТОЙJ
Deferoxamine Loxicily.
E-L: This 72-уеагч)к1 wmnan oumjj larnud of gradual onsel
ot" blurred vision in bolh eyes, and yellowish discoloration of
vision ["or 2 monlhs. Her visual acuity was 2U/20 2 months
prior Ю preseritalion. Her vision had dropped now lo 2tV25
in the right eye and 20-44) in the lefl eye. The tLmdus in bcjflh
eves showed penpapiI!a ry areas o f KPF: moll I ini’ lhal were
mofe visible on Ihe red-free photographs it and Fi. A lluorcs-
cein angiogjam showed Jeopard spcH-like pi^nentary changes
corresponding to lhe pigment molllinj^ (G ai>d l-l . She had a
hislory oi' sideroblastic anemia and had received inlravenous
desferrioxarnine tor 5 monlhs lor iron overload secondary
lo blcod Lranhtusicjns. ih e conlinmid 1u develop pijjmtffifcary
changes in the.1 macula (I to Ll. Her LFiG showed subnor­
mal rod and соле funclicm wilh decieiist’d ampliludes and
increased latency, HumpEiruy visual field showed en larked
blind spuL w ilh central visual field suppression.
■ ■ Й i
i t jn d U. F-jnnm (..'unninuhiun el 3.1. ) (E—L, ш иrimy ol Ur. S4!£nu
H .t ri г.r;.t U. I
D E F E R O X A M IN E M A C U I.O P A T H Y
IrtLra4tenou| adminislralion of deferoxamine mesylate
[Db"Q), 3-12 gjl4 hours, for Lhe treatment of transfu-
sional hemosiderosis has produced rapid onsel of visual
loss.; color vision abnormalities; nyctalopia; a ring sco­
toma; reduced electrorelinographic, electro-oculographic,
dark adaptation. and visual evoked responses; and mid-
Lo high-frequency hearing loss of cochlenir type.'11" ''
JTie fundi may be normal initially or there may be a
slight gntying of the macula (figure У.05А). both eyes
are affected. Visual symptoms usually begin 7-10 days
after the last treatment. Development of maculopalhy
may occur after chronic subcutaneous injection of def­
eroxamine.'1 fluorescein angiography soon after the
onsel of visual symptoms in the presence of a normal -
appearing fundus may show progressive staining at the
level of the RPU in the macular areas, and in some cases
Eeakage of dye from the optic disc vessels [figure 9.0SH
and C). Pigmentary changes usually appear within sev­
eral weeks (figure 5vp5D), After cessation of treatment,
return of visual function осшгь over 3-4 months and
approximately 70% of patients recover normal acuity.
Two 70-year-old patients developed pseudovitelliform
Eesions in the macula of both eyes while on low-dose def­
eroxamine.'" Reversible HOG changes have been no Led/"
and a drop in the Arden ratio to less than 1.5 was seen in
another palient on DE'O for 1 years. On cessation of DPQ
following splenectomy her LOG and visual acuity returned
to normal hence l:.OG at regular intervals may be used as
a monitor for Loxicity. 1 Some patients show increase in
both rod and cone implicit Limes and reduction of a- and
b-wave amplitudes.1 "1'['he Lnecbanisni of retinal toxicity is
unknown. Although chelation of iron is unlikely to be the
explanation, removal of other metals, particularly copper,
from the Rl’li may be important/’1'-1"11 Copper fluxes may
cause oxidative cell membrane resulting in lipid peroxida­
tion products that are toxic to the RPt. Copper movement
into extracellular fluids may interrupt monoaminergic
neurotransmission in the retina.’"' Light microscopic and
L ilt r a s t r u c t u r a l changes in the R l?E in an eye of a patient
studied after recovery of visual function included patchy
depigmentaiion and thinning, loss of microvilli from
tbe apical surface, vacuolization of the cytoplasm, swell­
ing and calcification of mitochondria, disorganization
5.03 Deferoxamine retinopathy^
A—D: H i is b4-year-old wom an w ilh chronic renal failure
and renal diiLiy iii developed severe osleoporosis lhal Was
LHolt^iL lo by reliited to excessive absorbed# of aluminum
from Ihe diaHynate used Lo Ireal her renal in s u ffic ie n c y
Following inLravenous; deferoxamine Lhe palient noLed dys-
c: h rcj-nin Lops-ins.. blurring o f vision, л ltd difficulty m reading. Al
Lhe lime ol" examinalton 1 5 day^ after he» intravenous; iher-
apy her visual acuity was 20,'JO. 5he had 10 ° central relative
scotoma la. Fundoscopit: examination showed sli^hL ^jay-
i'n^ of the relina paracenLrally (A). Fluorescein angiography
showed a mottled pattern o f hypeifluonescenoe Ihrouyhoul
lhe macula anti a cenlral area of sLaininy a I lhe level t vl" Lhe
hih’t -Li and C:-. i>he noled rapid improvement of her vision
st^on afler her examination. W h e n seen S m onthi laL-er, her
only com plainl was mild dyschromatopsja anti her visual
acuily was 2СУ20 in the riyht eye and 2 0 ^ 5 in the left eye.
There was mollling of Che Ы Е in Lhe m acular areas; of holh
eyes 0 ) .
E—L: This 80-year-old m ale suffered from myelofibrosis for
Lhe pruviousi T year*; and received deferoxamine (Dcsfe.r^Ej a
year laEer. Six l a eijjhl weeks follow ing iniLfaLion of Desferal
he noliced rapid developmenl o f circum scribed circu­
lar scoComas in bolh eves w ilh progressive worsening. H e
underwent C aiaiad exLracLion in ta>Lh eyes i monlhs I filer
wiLh improvement of vision lo 20/oQ O U . Vi sun! deteriora-
Lion continued, he was switched Lo deferasirox 1Exjade) 9
months later w hen his vision was 20/200 in both eyes.
Coarse pLgjnenl clum ping in lhe fovea and diffuse pig­
ment m o ilin g throughout lhe posLequaLorial fundus were
noled. l:luojescein angiogram revealed piemen I alteration
anti disrupted RI-’E: in Ihe fovea. Goldm ann visual fields
w ere full peripherally w ilh cenlral scoLom<ts of 10-15 O U .
Electro rtlinogram showed marked dricnease in rod function
I'd it !l id m criT.Hi d'-t revise n <
. one И-п< 11>'■:i. ■h- i pp^-'
and j in c levels w ere normal, he had no hearing problem,
and Lxjade could noL be discontinued due Lo iron overload.
He was started on AREL35 fage-related eye disease sLudyt
viLamins.
of the plasma membrane, and thickening of Bruch's
membrane.1''0
More recently an oral agent hxjade is being used as a
chela LiLig agent in patients receiving repeated blood trans­
fusions. I'igure 9.05E:-1. shows a palient who continued
lo develop macular and exlramacular pigmentary changes
even after being switched to lixjade. High-frequency senso­
rineural loss and bone dysplasia are other features of def­
eroxamine toxicity.
S ID E R O T IC R E T IN O P A T H Y
If iron-containing foreign bodies enter the eye, lhe iron
may become oxidized and be bound lo lhe ocular tissues.,
producing either localized siderosis or, particularly when
the foreign body lodges in lhe vilneonetinal region, diffuse
ocular siderosis (ligure 9.06А—K). " e Evidence of ocular
siderosis includes pupillary mydriasis, darkening of lhe iris
(t igure 9.G6D]; and orange deposits in lhe anlerior subcap-
sular region of lhe lens. Posteriorly, hazy ocular media may
preclude visualization of the fundus, liarly optic disc hyper­
emia and fluorescein angiographic evidence of leakage may
he present. Later a picture simulating pigmentary degenera­
tion of the retina and progressive loss of peripheral visual
fields may occur (figure 9.06A and H). Ihese changes may
he associated wilh oplic disc hyperemia, lletinal vascular
Harrowing and occasionally microangiopathy with vascu­
lar occlusion and leakage are seen..''"" Abnormalities in
the I:JIG eventually occur (Figure 'J.06H) and may be revers­
ible Following early removal of the intraocular iron foreign
body.31"94 Histopathologically, the iron is initially depos­
ited primarily in the inner relina and KFH. .Eventually, how­
ever, degeneration may affect all layers of the retina.
The natural course of a retained intraocular iron foreign
body is variable. In some cases the foreign body may be
absorbed or become encapsulated and the siderosis may
stabilize or regress.11" M In some cases the hyperpigmenta­
tion of the encapsulated mass may simulate a choroidal
melanoma [figure 8.11 ft-E:]/' hi general, intraocular iron
foreign bodies should be removed, particularly from an
eye showing evidence of siderosis.1'' Removal of foreign
bodies deeply embedded in lhe ocular wall or of largely
oxidized foreign bodies may be difficult or impossible.
An acute pigment epitheliopalhy, serous relinal detach-
menl, and Iransienl visual toss occurred in a paLient wilh
svslemic hypertension and chronic glomerulonephritis
after intravenous adminislralion of iron debt ran/0
Experimental injection of iron powder or iron-containing
solutions into the vilreous may produce acute geographic
areas of retinal whitening (figure У.061:-К]. fluorescein
angiographic evidence of severe disruplion of lhe RPE
Siderosis bulbi.
A-С: This man. was blind in lbe left eye been use? of siderosiis
fo Hewing Iwt) unsuccessful attempts at removal of л r e fin e d
inlTaoLular foreign Eiody H yea re breyhrtisfifr Note the severe
atrophy o f lhe reti:na and relinal pigment e p iIhelium iKPI-
and the delayed perfusion o f lhe rulina ;tnd choroidal blood
vessels anjjioyraphicaily lA and 111. UEtr-asonograpEiy Itl) co n ­
firmed the presence of the? foreign E>ody. The elecLrorelino-
^ram extinguished in Ihe lefl eye.
D and E: th is 44-year-old construction worker wEwj ham­
mers metol on metal noled ,fhis eyes- were Lhiinjjinjj." The I el I
iris is sideroLit [Dj. His- viHUfll acUHV 20/2(5 in the ri^hl
eye Lind 20/70 in lhe Jefl. Visual lield w as full on '.he ri^hl
and tonsLricled on the lefl side. An fcKG SflOtatt significant
decrease in scn U p ic And p holc^p i-и fundi о л wiLh delayed rod
implicit Lime and decreased rod and cone amplitudes ■Ii).
Acute siderotic maculopathy in a primate.
F-K: This squirrel monkey developed a circular w hile area
in Ihe rmicuia 1 day .^fler lhe intravitreal injection o f 0.00 гущ
iron iLS ferrous chloride D . Huorencein an^io^rapEiy revealed
transmission a i Lhe cboroitLil Fluorescence and later in-Lenne
Hlrtinin^ in lhe are-a of tEiis whitening 'G j. TwenLy-ei^hL days
lal-er ihere was a circumHCribed area of КИ. depigmenla.tion
surrounded by a halo cf Ev,'perpv.>menta:L3on in lhe m acular
area (3-1). A w indow defecl in Lhe RFLi was evident an^io-
^rapEiically IL.',. A ph.as£-cont£jM micrograph made I s a y after
inlravitrea] injection of iron ptjwder showed pyknosis; of the
OLiler relinal cel] nuclei and edema c f the inner reLina (Jj. A
phase-conlmsl rftTt^dgraph days following inlravilreal
injection showed a sharp dem arcalion beLween Lhe normal
and atrophic outer retinal layers in lhe macular region (K 1.
| Л —C . L ' j L i r l L T V Г>1 I J r . Se-Lrf K . S r iC L J U : L J . M l 11 I : . . rt f L A 1
! :il> . ' l h y
O Ih t ji: I j n d К C n jn i M . L v c iu lh d a l.. l A j b l Ы ж с ! Y v iL h p t T i r n r a i a h f u jn t
I Ih .1 A r m n c .m lu u r n .il o f f J p h h .L lr r n r i^ liL ( l | i f ''h , 4 n i i .
ГиЫпМш ■Си.
(I'igure 3.06c],, and a diminished or non record able ERG
within the first Z4 hours of the inieclion ''' A zone of focal
atrophy of Lhe RPL surrounded by a zone of pigmenl epi­
thelial clumping develops wilhin a few weeks [Figure 9.U6H
and ]). 11istologically the primary damage is to the receptor
cells and НРЁ (I'igure У.06] and K). Retinal damage is much
more severe wilh ferrous than with ferric compounds.
 Szcteroflt WL'frjju^’rcWjif 769

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SCSfflffl

Ш Ш
C H A L C O S IS M A C U L O P A T H Y
Patients ТЛ1Lth jn intraocular copper foreign body may
show a xvide spectrum of reactions Lo its presence. In die
case of ni copper alloy, the inflammatory reaction may
be minimal and a slow diffusion of copper occurs and
ttnpregpate^ limiting membranes Of the eye to produce the
picture of chalcosis that may include peripheral comeal
ring sunflower cataract (see Figure fl. Ill], and heterochro­
mia of the iris.l| ' ' In addition, irregular yellowish-go!den
flakes may be deposited in the macular area away from
[he site of the foreign body (Figure 9.07A and B )tSLr5:i it is
presumed that these apparently Inert deposits are either
copper carbonates or oxides. '.Ihey appear to have little
effect on visual acuity. Their Eocation Is uncertain, but they
appear to be deep lo the retinal vessels. I'hese flakes disap­
pear after removal of the foreign body (Figure У.07С].Г' ' ■
ihe tR G is subnormal in approximately of patients
with chalcosis.
lixperimentally, copper has been found in the macro­
phages within the retina, in Muller cells, and in granular
clumps scattered throughout the retina."' 4 Clinicopalhologic
sludy in eyes with retained copper foreign bodies show cop­
per deposits in Descemet's membrane, vitreous, internal lim­
iting membrane of the relina, and fibrous capsule around
Lhe foreign bodies. Кyes with foreign bodies containing more
Lhan S.v'o copper show more disseminated coppcr --m Ls
and eyes with alEoy containing less than 35% copper show
more localized deposits. EtetinaE structures are usually well
preserved, even In eyes with an intraocular copper foreign
body retained for 22 years.9'
A R G Y R O S IS ___________________________
Argyrosis may be associated with discoloration of the
skin, mucous membranes, and many of the body organs
occurring with application of colloidal silver-containing
eye drops, eyelash tint, In photographers, photochem­
ists, miners, silversmiths and Industrial workers using
silver<onlaining compounds. When this discoloration is
confined lo the eye fotlowing, topical application of si Ever
9.07 Chalcosis.
A-С: Cupper deposilt in tht1 тп,юи1л of an 1fi-уедг-оМ
patient with а рек-lerior dislocated leh's. Ht1 tusfainyd an
inliaocular и о р р и torei^n-body injury 5 yeais prcviouiEy.
The*e deposits disappeared 14 months- after removal i)f Lhe
foreign body (CJ. His visual acuijy was 20/20.
Argyro sis.
1): Bluisti discoloration о й he conjunctiva 'argyrosis':.
E - G : □arlt choroid fGj a ssociated w ilh argyros-is of Bru ch s
membrane in a palienl w ilh systBiflft; argyrosis caused by
using a mouth wash containing stiver (Cullargenl Acel-arsol^
Snirbach, Suresrtes, Frarv.e'l 2 limes a day for 3 years. Red
light phologiaph shows no details o f choroidal circuJation
rind leopard spot pattern of I be fundus temfioraliy Ct) that is
accunlualed in l-he infmred fight photograph ifV
H: Photomicrographs showing argyros-is of lEie relinal pig­
ment epilhelium and EiruclVs. membrane :,ifrowsj.
lA - C . F f t jh i L Jc iI.m e y , ' t S lid Ц iT iim C. ( j h L ' n t ' [ . : i . ' H , :ru m Si m t h ur
L'l A
compounds lo the eye. the blue-gray discoloration of the
conjunctiva and cornea [Figure ^.07L>) is referred lo as
argyria. The discoloration is caused by deposition of sil­
ver in the basement membrane of the conjunctiva and
cornea, as well as In Descemefs membrane. Occupational
exposure in a silversmith from Etaly was found lo deposit
the metal in the endothelial basement membranes of the
coniimctiva and deep corneal stroma just anterior lo the
endothelium."1, I’eripheral and central or diffuse corneal
deposition has been noted, with the central involvement
occurring with longer exposure. E’atienls with argyrosis
caused by chronic ingestion of silver-containing com­
pounds may develop discoloration of the skin and body
organs, as well as loss of the normal choroidal markings
in the ocular fundus, a ‘'dark” choroid fluorescein angio-
graphically, and a leopand-spot mottling of the ocular fun­
dus when viewed with red-free light [E'igure y.07F-G)."
These fundus changes are probably caused by loss of trans­
parency of Eiruch's membrane as a result of deposition of
silver in the membrane [Figure 9.07J I).’07-''1- 3he discolor­
ation is permanent and chelation therapy is ineffective.
агэдпнй 771
C IS P L A T IN U M A N D B C N U
(C A R M U S T IN E ) R E T IN O P A T H Y
Intracarotid arterial chemotherapy witfa B^NLJ (ЬЗ-Ьгз-
[^2-chlorelhyl)- l-iiltmsourea], 30£>-400mg, and paplaH-
num [f?s-dtammiue dichloropEalinum(IE}), 100 mg, is used
for treatment of re-current malignant j;]Lcunas of the brain.
Jhis may cause precipitous ipsilateral visual loss and fun­
dus changes of iwo different types. Patients receiving BCISJL]
either alone or in combination with cisplatmum may
develop visual loss associated with ophthalmoscopic signs
of relina) infarction, retinal periarteritis and phlebitis, and
papillitis.'-1" '"" A retinopathy si mi Ear lo interferon retinopa­
thy with severe bilateral retinal ischemia leading to retina!
neovascularization has been described (E'igure 9.0SG-J].k!
Jlte mechanism of the vasculopathy is t>e]ie\red to be from
increased platelet reactivity to nonaggreg^ting concentration
of the agonists involved in the arachidonic acid metabo-
lisjn (increased thromboxane synthesis and early onset of
platelet aggregation wave}. 'Hie retinopathy was found to be
reversible or stable; however the field defect and vision loss
from optic neuropathy progressed even after discontinua­
tion of the drug.'' 4 Other findings may include ca\remous
sinus syndrome, partial sixth- and third-nerve palsies, severe
conjunctival imt4'Uo:i :.vA diLiim-sis. pain, aiu:. secondary
glaucoma. Approximately С5% of patienLs treated develop
these findings accompanied by visual loss abouL 6 weeks
after the start of treatment. Once visual loss begins it is usu­
ally progressive and severe.
Inlracarotid infection above the level of the ophthal­
mic arteiy does not protect from development of ocular
complications.^1'1 Those treated wilh cisplatinum alone
or in combination wilh LSOlvLJ may develop visual loss
associated with a pigmentary retinopathy wilh a cen­
tral scotoma, and later diffuse constriction of the visual
fje]d_w. -[’he may |-ie nonrecordable in some
patients.-" 1|,л' l"he visual symptoms and pigmentary
changes are usually mild following administration of tris-
platinum alone and appear lo be potentiated wiLh the
9.08 CispEatinum and bleomycin chorforetina! toxicity.
A-E: Th is- -tb-yeai-old man had л righl-sided inLracafейid
injection of cisplatinum and bleom ycin fur Uealmenl o f a
glioEjkaaloma c f lbe L?tei iп-. Н у noled I bn- й т т а д щ Ц нопк st ion
of heal Ejehind 'lie iрыi lalem I eye, and transient paralysis of
the righl arm. O n e d;*y lafe" fie noled visual I cjkh in lhe right
eye. tight days laler fiisUa) acuity in Ihe rigE^ е Уе Was I'gbt
perception only. The left eye was norm al. Examination of Lhe
rigbt fundus revealed tw u li/ira of Lhe oplic dii-c, fia rro w in i
ol lhe retinal vessels, and subtle rc*liпннI pigmnnl epitheliunit
iKJ't- moLlling ihsl m ofe appajjCn I an{j?p$rapbically Л
arid Ё ■
. t.i^hl djiys later Visual acuily was band BW van en l^
and 1hii re wan prominent mottling o f the RPt t-E.i.
F: This ^ Ё -yea^pld man experienced rapid visual losa 2
weeks previously several days following a left-sided inLra-
c:nrolid injection of cispJaLlnum and bleom ycin. I-Eis visual
acuity was 2Q/20 right eye and 20/400 Eefl eye. Note the
mtsilling of the K l’t in lhe left n'.acula.
G —|: This pa lien I received polycEwmotherapy ibEeomycin,
elupostde, and cisplalin) lor a recurrence o f germ cell tes­
ticular lumoi. Ten weeks afler LreaLmenl, he fosl vision in his
lefl eye. He Eiad bilateraE w idespread retinal ischemia vvilb
CcrtLxi-wnol spoLs, superficial relinal h e m o n p ^ , m icro­
aneurysm formation, and neovnscularizaLlon in lbe lefl eye
(С, Н]. Fluorescein angiogjapEiy revealed palchy bilateral
retinal ischemia, leaking capillaries and microaneurysms and
enlarged foveal avascular io n e with area* oi N V L on lhe left
(I and Jf. Systemic causes were thoroughly investigated and
excluded.
I- C i- L J - г м т K w . - in 4; l ; i l , | l : l
addition of BCrvU.l<t0 Hgure 9.0SA-]: shows pigmentary
retinopathy in two patients treated wilh cisplalittum and
bleomycin, A similar pigmentary maculopathy has been
reported after a combination of intracarotid injection of
mannitol and methotrexate together wilh intravenous
admLnistration of cyclophosphamide.11'1Mannitol disrup­
tion of the blood -ocular barrier was thought lo be instru­
mental in the macular changes, which lypically do not
occur with use of (he two drugs alone (see Chapter 13].
T A M O X IF E N R E T IN O P A T H Y
llimoxLfen citrater a nonsteroidal anliestrogen, is used lo
Lreal patients with breasL carcinoma and more recently ль
high-dose therapy Гог brain tumors.111 Patients who receive
high doses tjf laLTtoxifen [total amount of drug 1л excess of
90gj may develop loss of central vision, tnacuJar edema.,
and superficial white refraclile deposits that are located
primarily in the inner layers of the retina (figure 9.09Af
Ii. D, and Ei}.1 ' There may be punctate gray lesions al
the level of the outer reLina and RPh that appear nonfluo-
rescent {hypofluorescent] angiographically (E'igure 9.09l:).
IJefraclile lesions are more numerous and larger in the para­
macular area, are more heavily concentrated temporal lo
the macula, and show some tendency lo clump. [Peripheral
crystals can occur in some cases. О С Г confirms the inner
retinal loation.Щ H ie number and size of the lesions do
not change afler cessation of tamoxifen. Ught microscopy
and electron microscopy show that lhe retractile lesions
are located in the nerve fiber and inner piexiform layers.IEJ
'Ihey are intracellular and stain positively for glycosamino-
glyeans, 'ihe lesions appear to represent products of axonal
degeneration. Histopalhotogically they are similar to cor­
pora amylacea bul are larger and more numerous in the
paramacular area than the peripapillary area.
'inhere is evidence that long-term low-dosage tamoxifen
may cause retinopathy. '114-122 [n a prospective study of f>3
patienls receiving a median dose of 20 mg'day tamoxifen for
a median duration of 25 months, four patients developed
retinopathy and/or keratopathy !0, 27r 31, and 35 months
after commencement of treatment.ij2 'lhe mean total dose
In these four patients was 14.4g. Decreased acuily, blEaleral
macular edema, and yellow-white dots in the paramacular
and foveal areas occurred in all four patients and corneal
opacities occurred in one palient. After withdrawal of drug,
aImosl aJE ocular complications were reversible," 5,132
lleier .ind соworkers found mild deposition of inlra-
retinal crystals in only two of 155 visually asymptom­
atic lamoxifen-trealed patients (mean cumulative dose
17.2g ).1'■ The two patienls wilh ciystals had a cumulative
dose of Ш.9 and 21.9g respectively, in severe cases OCE'
shows intrarelinal pseudocyst formation similar to those
seen in idiopathic type 2 juxtafoveolar telangiectasia.,
likely from axonal degeneration of Muller cells and photo­
receptors. h''11",l2' The pseudocysl gradually enlarges with
ruplure of Lhe inner layer to result in a macular hole." 1
Transient bilateral optic disc edema, retinal hemorrhages-
and macular edema may occasionally occur after starting
low-dose tamoxifen d g l|^ ]J tlS-s30 Multifocal ERC done
prospective ly to monitor for macular loxicity is nol useful
even in patients who develop ciystals.1' :
O X A L O S IS _____________________________
Oxalosis is lhe deposition of calcium oxaEale in vari­
ous tissues of the body. Lhe eye may be solely involved
or may be involved as pan of systemic oxalosis. Systemic
oxalosis тчту be lhe result of: ( I ) a primaiy hyperoxaluria
9.09 Tamoxifen relinopalhy.
A—C : Fallowing a mastectomy far breast carcinom a (his
wom an песеты ! я tola I dose of tamoxfferi (ivt'ra period
□I 9 yeary. Her visual acuity was 20/20(5 in lujlh eyet. Nole
the intraretinal crystals are mure prominent in Lhe left eye.
D-F: This Ь З -year-old wum an, w h o received в Lota I dase of
between 30 and 150 g 1amo\ifen aver a period o f 29 months
fur treatment of meiasLatic breast carcinom a, noted loss of
oenLraE visfem. Visual acuity was 20/50. There w ere superfi­
cial white felrat.Li.le deposils lhal appeared Iо be in lhe inner
layers o f the relinas ot" bolh eyes (D and t.. NoLe also Lho
white spoLu in the periphery of lh e m acula IhaL angitigfaphi-
cally appeared honlluorescent IF>. La L-от phase an^iogramh
showed Jjys-Loid inaculaf edema. Five m onlh? p fotioush her
visual nicuily h.id been 20/30 in the rij^hl eye and 20/23 in
(по left eye and lh e fundi w ere normal.
Secondary oxalosis.
G and H : K etin al ox alo sis in a 34-year-old w o m a n a lte r 2
w a r s ol in haliH ian ab u se o f m o lh u s y liu ra n e . There W e re m u l­
tip le bright y e llo w - w h ite crystals throughouL Lhe retina an d
p ig m en t e p ith e liu m w ith a retinal arterial a n d p eriarterial pre-
d ei:Lii)n ih e subsequently devei< red " i ll I/. i., : - K id tiey
b io p sy re v e a ie d birefrinj^em crystals in lh e renal 'u h u le lum ens.
I - L : R e ; ■i (jsaEosis in a 6 3 -year-old m a n w h o d e v e lo p e d
re n al fa ilu re f o llo w in g m e th o s y f lu ia n e a n e s th e s ia Hi. Ho
s u b s e q u e n tly d ie d , a n d his eyes w e r e o b ta in e d at au to p sy.
N o te lh e b ire frin g e n l o x a la te c ry s ta l? p resen t яп Lhe reLina
jn lh e m a c u la r re g io n , in Lhe retinnil pig^nenl e p ith e liu m ;K .
a n d in Lhe k id n e y :L I.
lL^-h l-nnm .Ml KL'Uh\n ri j I. I4t i .hii-1 H, Irum Nuv.ik (j[ л!.'-'11-L.hmrn
I ' m; Inch liiil I AlhKiri'"' 1W7S, Лгпигк .in Mudictl A^-.c* i.iinnn. All iii^hla
hcuerVtd.)
secondary lo an in horn error of metabolism lypes ] and 2
(see Chapter 5); (2) a toxic reaction to ethylene glycol or
methoxyllurane general ^de3thesia;i:!i-12fl or (5j chronic
renaE failure and h em o d ialysis.O cu lar involvejnenl in
secondary systemic oxalosis has been observed afler use
of methoxyflurane, which is л nonflammable anesthetic.
When administered to patients with renal dysfunction
and particularly if administered over a prolonged period
of time, it may cause irreversible renal failure secondary lo
lhe metabolic breakdown of lhe aneslhetic lo oxalic acid
and fluoride ions (figure 5.0УК). These patients., as well as
those With primary hyperoxaluria, may develop numerous
yellow-white, punctate, crystalline lesions diffusely scat­
tered throughout the posterior pole and mid periphery of
lhe eyes (see figures 5.67 and 9.Q2G and II). En some, the
crystals appear to be mosl prominent in Lhe pigment epi­
thelium wilh surrounding areas of hypertrophic and hyper­
plastic Rl’fc (figure 9 $ 9 l},^ 6'137 and in others, along the
retinal arteries (figure 9.09Gl.IJ:i-!-: I.ess commonly the
crystals are intraretinal, and oplic atrophy is seen occasion­
ally. In paLienls wilh methoxyflurane toxicity the retinal
and pigment epithelial crystals may occur in the absence
of changes in lhe oplic disc, the macula, and the caliber of
lhe retinal vessels seen in primary hyperoxaluria (see figure
5.67). fELstopalhologically. the Aecks seen ophihalmoscop-
ically are calcium oxalate crystals in the ЙРЕ, murosensory
retina, and ciliary epithelium (figure 9.09] and K }.|J'
 'lhe different]al diagnosis includes the other foftos of so-
called flecked retina, .including Eieltis crystalline dystrophy,
nephropathic cystinosisr canlhaxanthine й^йора^Ьу; West
African crystalline maculopalhy Sjogren-(.arsson's syndrome,
talc Fetinopdthyr fundus al bi pnnctatus, retinitis punctata albe­
scens, Slaigardl's disease, Alport's syndrome, bilateral acquired
juxtafoveolar telangiectasis, and vitamin A deficiency.
Calcium oxalaLe crystals may be found wUhin the retina
as an incidental finding in patients with Long-standing ret-
ЁИч11detachment (see Chapter 1, E'igure 7.3] A and li) and
with morgagnian cataracts unassociated with evidence of
systemic oxalosis.
C A N T H A X A N T H IN E
M AC U LO PATH Y
CaEithaxanlhine is a carotenoid dye used in food and
drug coloration. Some patients who use il orally (usually
a lot aI dose of lUg or more xvithin 24 months) as a tan­
ning agent may develop a symmetric distribution of golden
particles in a doughnut pattern in the superficial retina
in the macular areas (figure 9.1Q)._,U" M' 'ihe retinal crys­
tals may be exaggerated in eyes with other diseases of the
fundus (i'igure y.lOD-E).1'^ A feu1 patients may develop
similar crystals in the cornea al the level of l>escemet's
membrane.1' 1Retrospective studies of pure canlhaxanthine
(Orohronze) consumers revealed an incidence of retinal
deposits varying from 12% to l4 w .lJ0jt32 The occurrence
of the deposits correlates with lhe total dose ingested. In
Lwo studies 37g canthaxanthine induced retinal deposits in
50Ч-0 of the patientsJ30 and 6Qg induced deposits in 1(Ю%
of patients.1,D Predisposing factors that lead to onset of ret­
inopathy al much lower dosage include focal disease of the
RPE,li] lja ocular hypertension/4 and concurrent use of
beta carotene (figure 9. iO tJ-l).' v llennekes reported the
development of canlhaxanthine retinopathy in a pa lie tit
wilh retinitis pigmentosa after IngesLion of 12-14 g over a
period of 4 months."11 ihe maculopalhy is usually associ­
ated with normal visual acuity buL reduced retinal sensi­
tivity.1i2 Some palienls may demons irate subnormal dark
adaptation and eleclroretinographic responses.l*Svl37-1Ji,]4J
ihe LRC changes in most palienls are reversible after the
ingestion of canLbaxanlhine is stopped.11' HOC responses
are norm al.';1, Nl-I+1-J-1J Fluorescein angiography is
typically normal but may show a bull's-eye pattern of faint
hyperfluoreseence (figure У.10С). Morphologically these
red, hirefringenl, and lipid-soluble carotenoid crystals are
located in the inner layers of the entire relina and the cili­
ary body.: Jhey are panicularly large and numerous peri-
foveally. where they are clinically visible. They are located
in a spongy degeneration of the in tier neuropil and are
associated with atrophy of the inner pans of Muller cells.
'Jhey presumably represent a canthaxanlhitie—1ipoprotein
complex.N:'
The Fetinal crystals may gradually disappear a year or
more after ingestion of canlhaxanthine is discontinued,
and some may remain for al least 7 years.1''1114,1w ’['he
9.10 Can Ih as an Ihi ne ret ino pathy
A - C : Note (he glistening yello w crystals arranged in a
doughnut shape in the superficial and deep relina in the
of ihis palienL w h o was л long-term user ol skin-
tannmj^ agents. Note the fierifoveolar ol" hyperfluo-
rescencu, w hich probably is caused hv ohslruuJion ot the
background fluorescence by lhe crvslnls rather th in dupi.q-
m enlation or lh e retinal р1фПел! epithelium (KPt).
D —F : Unilateral deposition of i^nlhaxanthine in Ihe righl eye
of ,i palienl w ilh recurrent idiopathic central 5егсщ> chorio­
retinopathy in the ipsilateraE eye (t> and Ff. Lefl eye is unal-
lecled :Eil.
G : Asym m etric canlhaxanthine retinopalhy occurred in an
asymplomalLC -year-old wom an w ilh an old inferior tom-
poraI branch reLinal vein obstr-u-clion in Ihe lefl macula. She
was tcjmplal'inii^g of blurred vision a Hid "lem on-yellow pin-
w liee!" pholopsia iTi the left eye. Visual acuity was 20/20,
rrjj.hu eye, and 20/40, lefl eye. There wore more crystals in the
left m acula and there wepe Inlriicorneal crystals in l>oth eyes.
She hiid la ken oral canlha*anthine for many vears.
H and l: Сал1Ьаяап[Ыпе! relinopathy associated w ilh
chronic recurrent bilateral idiopathic ce n ta l serous chorio­
retinopathy. H e took canlhaxanthine, one labtel per day for
4 months, 15 years before these photographs. Visual acuity
was 20/3OOr light eye, and 2U/25, 3efL eye.
I and K: Crystalline relrnopalhy identical to that caused by
сил Ihaка nthine in a 4B-yenr-old man w ilh no history of sup-
p lemenlaJ ca nlha лапth i ne.
L: M ild unilateral crvslalline relinopalhv lairtnv of unknown
ciiu.4f in a m iddle-aged man.
( A . l r n f К . I-ITOTI ( !r>r: : n C t ,1 I . 1 I
delay in reversibility is in keeping with the observation
that the plasma concentration of canthaxanlhine lakes al
least 9 months to Fecover to normal levels in patients hav­
ing received daily oral dosage of I GO mg for 3 months.N'
lhe return to normal values of static perimetry threshold
in some patients suggests that the abnormality is not the
result of an irreversible anatomic alteration, as suggested
in experimental studies in rabbits.1л ' r,i
Retinopathy identical to lhal of canlhaxanthine reti­
nopathy may occur in some palienls without a history of
extradielary intake of canlhaxanthine (figm e y.OSf and
K }.10-3 Similar retinopathy has developed in one patient
receiving long-term nitrofurantoin therapy.111?
Administration of amounts of canlhaxanthine compa­
rable lo those ingested by patients developing can thaxan -
thine relinopaLby produced morphologic changes in the
retina of rabbits and cats, but no retinal crystals.150 '■
'lhe cats developed a progressive orange sheen lo the
ocular fundus lh.it morphologically was associated wilh
increased RETL cell height and vacuolization caused by
enlargement and disruption of phagosomes.1^ Dose-
dependent ingest ion of canlhaxanthine in cynomotgus
monkeys has shown accumulation of the crystals in nests
and rods within ganglion cells near the ora serrata and in
the macuEa.i5!i An ultrahigh-fnequency О СГ showed the
crystals lo be in superficial je f ln i116
W E S T A F R IC A N C R Y S T A LLIN E
M A C U L O PATH Y
Llderly patients from the Igbo tribe in Southeastern
Nigeria in Wesl Africa have been found la deposit preen
or yellow,: refractile, foveal crystals (hal are bilateral and
asymmetric in distribution.' Subsequent reports have
found the crystals in several West African tribes, includ­
ing those in E.iberia. Ghana. and Sierra E.eone.' " L'hese
crystals are found in the inner retina, mostly in the fovea!
inner plexiform layer, and do not affect vision or elec­
trophysiology of line eyes [l i^uie Я.И Л -Ь).1' " |S9 O C t
can demonstrate the location of the crystals,. seen in the
superficial retina in figure 9.11L Most pa Lien is are older
than 50 years of age. ihe original description of the con­
dition attributed the crystals to ingestion of kola nuts.
H o w e v e r . . only one of three patients had a history
of ingestion of kola nuts more than 20 years previously,
fifteen of the 20 patients reported so far and two others
(Figure 9.11A-E) had diabetic relinopathyr one sickle-cell
retinopathy,. one branch retinal vein occlusion (1JRVO),
one familial exudative vitreorelinopathy [HSVRJ, and one
other patient of Пг. Ediviit Ryan Eiad a branch retinal vein
occlusion; it is conceivable that the hyperpermeability of
their retinal vessels may have facilitated lhe deposition of
the crystals. AH reported cases thus far have found crystals
ill the macula; however figure 9.1EK-I] iElustrates e>ttra-
macular deposition of crystals in lhe vicinity of the flat
new vessels in this patient wilh proliferative diabetic reti­
nopathy. Eler brother with, nonproliferative diabetic reti­
nopathy has macular crystals only
N IT R O F U R A N T O IN C R Y S T A LL IN E
R E T IN O P A T H Y
Nitrofurantoin macrocivslaE used for a prolonged period
(] 5 years) in a patient resulted in deposition of the shiny
crystals in and around the disc and macula in both eyes,
l i l t antimicrobial is used lo treat urinary tract infec­
tions. Its chemical structure delays dissolution and hence
remains in a crystalline form and may become deposited
on prolonged use.11'0
9/11 W esl African crystalline maculopathy.
А—С : Агт asymplomalH: Аb-yt»ar-o]d man from Laf’.ot. Ki^eiia^
with а 4-year history of noninsulin-deperiderit diabetes meE-
Ntus and hypertension was seen in M ay 100j!. He had Езееп
living in lhe U S A for 5 years. H e denied renal disease. intra­
venous druji им?, hislory of es|jusure to general anesthe­
sia, nslrofurantoin use, or iMesffetin pf cjsnlfvaxanlhine or
tamoxifen. A hisLory o f kola nul in^eslion was remote and
infrequent. Visual acuities were 2£V20 G U . Fundus showed
moderate nonproliferative diabetic retimjp.ilhy fji laterally.
In add il ion to :nacu3ar exudates most prominenl tempo-
raJiy, refraclile yellow ц.гееп cryslals. were noted in lhe fovea
of bolh ayes lA and E 3 N o cryslals were noted oulside the
m icijla r foj’iti-n. H u subsequently developed clinicallv sif^nifi-
L'anl macular-edema bilaterally requiring focal laser treatment
in 2004 w ilh nosohilion or ihit? macular exudales. and edema.
Four years later, despite resolution o f macular edem a and
absence of leakage on fLuorescein angiography, Ihe foveal
i rvstals have p e r s ^ W with sotfte shift in I heir distribution
D -L: H is 5 9-year-old sis-Ler was evaluated in March 200ti.
She had a 12-year history of diabetes meflilus with insu­
lin use over tHje previous 2 years. Shu was a 1st) from Layoi.
Nigeria, and harl been living in 1he U S A for .3 years. N o
definitive history of kola nut ingestion could he elicited.
Visual acuities are 20/50 Q D and 2(V4Q O S. She had 24-
nuclear scEeroLic cataracts bilaterally. Fundus exam showed
nonproliferative diabetic retinopathy hila!erally With similar
neftactile ye llo w green crystals in Ihe fovea o f both eyes IL5
and E). There w ere na m acular exudales or edema in either
eye. Very little exLramacular crystalEine deposits w ere pres­
ent. She underwent uncomplicated t a b r i d extraction wi:h
posterior-chamber lens im p larlalio n in bolh eyes in J-u-iy
20t>&. In Sepl ember 200^ visual ao4tipS w ere 2Q-,4 0 01>
and 2 0/3 0 05. Slit! developed early proliferative diahieLic
relinopaLhy with areas of llal N V E in the nasal and temporal
m itlperiphery of both eyt4-. The cryslals were now noletl bolh
in the m acula as well as the mid periphery with clustering of
Lhe depos-ils adjacent to areas of flat N V t lF-]j. An^ioLjram
confirmed the M Vt .J and К . O ptical coherence tomography
esa mi nation demonstrated lhal the crysla3line d e p o s it were
located in lhe superficial inner retina L.I. Another 35-year-
old sislef '.one ol six olher siblings w ho was visiting from
Nigeria was. examined in February 2003. SI*ej hatl no ocular
complaints and no his lory of diabeles, liyperlension. or other
vascular disease. Her relinal examination was entirely nor­
mal with no evidence о I crystalline deposits.
lA-L, ( ciurlL'i-y uf l>r. Ь in ArrinddllJ
F L E C K E D R E T IN A A S S O C IA T E D 9. i2 Xerophthalmia^

W I T H V IT A M IN A D E F IC IE N C Y A -L: A б З -уидг-Dld male w ilh щ known history of pernicious

anem ia for tO yeart presenled w ilh pfogressive ni^hL blind-
P a tie n ts w ith v ita m in A d e fic ie n c y secondary to in a d ­ г ё Ц tor IE rciDciths. H e was receiving biweekly bhoLh o f vila-
e q u a t e d i e t a r y i n t a k e , m a l a b s o r p t i o n s ta te s r e s u l t in g f r o m min- L5|2- His visual acu ily was 20/30 O L ; color vision wns
subnormal. Fine [{ray w hile doLs were seen in boLh fundi, dis­
c e lia c sprue, re g io n a l e n te ritis, je ju n a l bypass s u r g e r y .,
tinct on red-free images ;A-F fcrnoWs)). Angiogram showed
c h ro n ic live r d is e a s e , h e p a tic tra n s p la n ta tio n and m o re
variable f !uorescence of the flocks yjggesling 1 Changes
re c e n tly w i t h b a ria tric su rg e ry m a y d e v e lo p n ig h t b lin d ­ were al thte pholorecepLor level rather than al Lhe pigment
ness. co rn eal xe ro s is , and a p e c u lia r p e rip h e ra l re tin a l epithelium (Li:-, biod and cone functions w ere decreased
c h a n g e c h a ra c te ris e d h y th e p re se n ce o f m u ltip le , y e llo w - on electrorelinoyram (ER G leslin^. Serum vitamin A EbveI
w h ite , som ewhat g ra n u la r s p o ts in th e o u te r re tin a measured 0.06 mu.'l (normal D.30-1.20 m ^ l) and retinyE

i 'ig u r e 9 .1 1 A , C , D , 3: a n d kj [fu n d u s Jie ro p h th a lm ic u s ;

palmlmlie O.OOmi^l {OnrmaJ < 0 ,1 "^ An upper and lower
^aslrointeslinnl sLudy w a s done. There w h s .limosl loLal viJ-
L J y e m u r a 's s y n d r o m e ] , ' 172 These fe c k s are o f v a rio u s
lout- aLrophy, and Ihe lamina рторпа was- infiitralud w ilh
size s a n d s h a p e s a n d s im u la te d ru s e n . J h e re tin a l c h a n g e s
mixed it^ a rm p to ry cells consisting. ol lymphocytes, plasmia
have been a s s o c ia te d w ith m arked c o n s tric tio n o f th e cells, and flrtnujocyles (H and 15. lh e garble and esopha­
v is u a l fie ld s (i'ig u r e 9 .1 2 ! I a n d i), ab norm al dark a d ap ­ geal mucosa was rVormal;, ihus Lhe previous diagnosis of
ta tio n , and e le c tro re Lin o g ra p h ic changes, in c lu d in g d is ­ pernicious anem ia was erroneous. A diagnosis of celiac dis­
a p p e a ra n c e o f th e a -w a v e f o llo w e d b y lo ss o f th e b -w a v e ease was made, hie received daily ini ra muscular injecLirjn^

and g re a te r r e d u c tio n o f th e s c o to p ic lh a n th e p h o to p ic of Aquasol A 100 0(50 uni Is for 3 dayv follow ed hy every 2
weeks. He was advised Lo follow a gluten-free diet. Three
re sp o n se s. E 'o I l o w i n g a d m in is tra tio n o f v ita m in A, (here
months following the diagnosis and treatment his nvcLnlopia
m a y b e e ith e r c o m p le te o r p a rtia l (fig u r e 9 .12 A and |-L )
had resolved, lhe bKC and v]sual field defects had improved,
re ve rsal of Lhe fu n d u s and e le c tro p h y s io lo g ic changes, and lhe w hile flecks had mosliy resolved (J).
d e p e n d i n g o n L h e c h r o n i c i t y o f t h e d e f i c i e n c y 1 ~ '['h e К and L: A b4-year-old w om an with If^A nephropathy requir­
fu n d u s c h a n g e s are m o r e lik e ly l o o c c u r i n t h o s e p a tie n ts ing dialysis, and cirrhosis secondary lo medications noted
w ilh vila m En A d e fic ie n c y who d e v e lo p e vid e n c e o f cor­ difficulty in the dark and in dim Ei^hLing over 1 year. Her

n ea l. x e r o s is .
uncorrected visual acuily was 20/40 and 21V50; color vision
Wnis ЗЛ 1 in each eye. Upper п-asal reflirra shows w hile punc­
llu o re s c e in a c ig Eo g ra p b y shows o n ly a m ild va ria b le
tate flecks of xerophLhalmia (arrow, k). Her vilam in levt'l w nt
flu o re s c e n c e o f th e fle c k s [E 'ig u r e 9 .1 2 G ) , s u g g e s tin g th e
O.Obmj^l fnormaE 0.3-1.2 mg/Ь. 5he received oral vilam in A
lo c a tio n o f Lhe fle c k s to be p rim a rily a l (h e p h o to re c e p ­ supplement aI ЁО ООО unils X!2 and her sytnptoms improved
to r la ye r; o n l y som e o f th es e m a y cause se c o n d a ry R P li in 3 days. Upper nasal retina o f right eye shows resolulion of
c h a n g e , a c c o u n t in g fo r th e p a tc h y h y p e rfiu o re s c e n c e . most ol Lhe flecks at 5 weeks (L'.
A n im a ls w ith v ita m in A d e fic ie n c y h is lo p a tb io lo g i­ IA , L i . l r, i J ); t . i n n u ^ / l . L i w t f c t i c i ) .r l h L j R l'I . i, .'! A l l . ! 1 S .ju r n f c r s JM 1 0 ,

c a lly d e v e lo p d is o rg a n iza tio n o f th e rod o u te r s e g m e n ts Ч 7& Д -7П 2 0 -*Ъ 2 0 -Ч , р.Эб Е. К and L , cuurtny or Or. W.wne W u jnrl Dr.
|-r.:n<.U h|.L''LL M i,l. I
a n d e v e n t u a l l o s s o f t h e v i s u a l c e l l s . i r , J El is p r o b a b l e lh a t
t h e t r a n s i e n t y e Il o w - w h i l e s p o t s o c c u r r i n g i n h u m a n s are
re la te d to th e m a c r o p h a g ic re sp o n se to lo ss o f r o d o u te r
seg m en ts and RL:H cell d is ru p tio n s im ila r lo th a t w h ic h
has been d e m o n s tra te d h is to p a Lh o lo g ic a lly to account O ne 5 0 -ye a r-o ld m an w ilh a c q u ire d n ig h t b lin d n e s s
fo r th e p e c u lia r ye] l o w -w h ite sp o ts th a t m ay be seen in a s s o c ia te d w i t h s te a to r r h e a w a s n o t e d l o h a v e t h e Ly p ic a l

p a t i e n l s i v i t h E . e b e r ’s c o n g e n i t a l a m a u r o s i s s o o n a f t e r b i r t h . changes o f fu n d u s a l b i p u n c l a t u s . '-h7 1 1 is a b n o r m a l dark

M a la b s o rp tio n s y n d ro m e s , in c lu d in g g lu te n e n te ro p a th y o r a d a p ta tio n curves im p ro v e d a fte r v ita m in A a d m in is tra ­

c e liac d is e a s e [Fig u re 9 .1 2J anti K ) , n u tritio n a l and o lh e r t i o n , b u t l h e f u u d u s r e m a i n e d u n c h a n g e d . A l t h o u g h it w a s

c a u s e s o f m a l a b s o r p t i o n , l i v e r d y s f u n c t i o n s u c h as c i r r h o s i s p o s tu la te d th aL Lhe a lb ip u n c t a t e s p o ts m a y h a v e re s u lte d

( f i g u r e 9 . L 2 K a n d I .J , a cid m o s l r e c e n t l y g a s t r i c b y p a s s s u r ­ fro m p h o t o r e c e p t o r d a m a g e a fte r c h r o n ic v i l a m i n A d e fi­

g e r y are c o m m o n c lin ic a l se ttin g s f o r v i t a m i n A d e fic ie n c y . c ie n c y , t h is s e e m s u n l i k e l y sin c e o th e r in ve s tig a to rs w h o

C o n c o m ita n t zin c d e fic ie n c y has a ls o b e e n im p lic a te d in h a v e s t u d ie d th is d ise a se h a v e n o L n o t e d p e rs is te n c e o f th e

Lh e p a l h o g e n ests o f x e r o p h t h a l m i a . w h ite s p o ts fo llo w in g Lherapy.
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A M IN O G L Y C O S ID E 4/13 G e n ta m ic in retinal, toxicity.

M A C U L O PATHY A—E: This 67-year-old man had accidental irrigation of the?

anterior cham ber w ilh O.^ml gentamicin instead of acetyf-
J l i t i n a d v e r t e n t i n j e c t i o n o f l a r g e d o s e s й -f g e n l a m i c i n i n l o chdJLnt after catEjracl exlraclion nind pi nt(?myn t or an inLra-
ocuJar lens. A posterior capsuloLomy was donu. Twenty
e ith e r th e л n t e n o r c h a m b e r a fte r c a ta ra c t e x tr a c tio n o r th e
minute* latef llit* mistake Was discovered, afin lhe anterior
v ilre o u s d u rin g a s u b -'le n o n 's in je c tio n m ay p rodu ce a
chamJjer was irrigated. Ih c> next day Lhe vision in lhe eye
r a p id a n d se v e re v is u a l lo ss a s s o c ia te d w i l h a p e c u lia r re li-
was ligjit perception only. Two days postoperalively (here
n o p a l h y t h a l is m o s t m a r k e d i n l h e m a c u l a r a r e a (Fig u re was corneal edema and a semropaque retina witb peripheral
9 . 1 3 ) l iJ:3" i , ! J Ч Ъ е p a l i e n l is u s u a l l y a w a r e o f p r o f o u n d lo ss relinal hemorrhages 1Л. Fluorescein angiography revealed
o f v is io n o n t h e J i r s l p o s t o p e r a t i v e c la y . J n i t t a l l y l h e f u n ­ extensive areas of nonperfusion of lhe relina in rhe posterior
d u s p ic tu r e m a y s im u la te l h a l s e e n in c e n lr a ! r e lin a l a rte ry pole (B and C ) and selective periarterial leakage larrows, C|.
O ne month posloporaOvely lhe cornea was clear. Гhere was
o c c l u s i o n . J h e r e is m a r k e d w h i t e n i n g a n d s w e l l i n g o f t h e
a Lh'.|ri"- -:»>t surrounded by a milky w hile retina,. dilated
re tin a in th e m a c u la r area a s s o c ia te d w ith a c h e rry -re d
tortuous veins, many rfsinal hemorrhages.. and pigmenlary
s p o l (I'ig u r e 9 . 1 3 D , f, a n d J} . O t h e r s u r r o u n d i n g areas o f
sheathing o f Ibe arteries iDf. Angiography revealed persis­
p a lc b y re tin a l w h ite n in g m ay be e v id e n t. R e lin a l hem ­ tence of lhe relin.il vascular hypoperfusion :t:i. Visual acuity
orrhages d e v e lo p and becom e m ore num erous ( l ;i g u r e was hand mo Yemenis, Six weeks later Ihe palienl developed
9 .1 З А . t; a E id [} . A l t h o u g h i n l r a v i l r e a l i n f e c t i o n o f le vels o f c>vjdenc:e of neovascular glaucoma.
g e n la m ic in up to 2 0 0 f:g w e r e p r e v i o u s l y c o n s i d e r e d sa fe F —I: This 99-year-dd man suslained an injiaoculnr m etallic
fureigji-body injury. After removal of Ihe foreign body tran-s-
fo r th e tre a lm e n l o f e n d o p h th a lm itis , m a c u la r in fa rc lio n
sderally w ilh a megnel, clindam vi in 23(Ji ^ and genlam icin
m a y o c c u r in s o m e p a lie n ts a fte r tn tra v itre a l itije c lio n o f
4 0 0 fig were Lnjecled inlravitreally. Ten hours posloperatively
0 .1 or 0 .2 m g g e n la m ic in s u n m f c lfl3 -ja JJe p e litiv e in je c ­
visual acuity Was 20/200. Thirly-two hours poKloperaLively,
tio n s o f n o n to x ie doses m ay p rodu ce r e t i n a l d a m a g e . 1 ''" lhe patient noted a dark cenlral scoloma. Six days poslopera-
K lu o re s c e in a n g io g r a p h y ly p ic a lly s h o w s a s h a r p ly d e fin e d LivoJy there was w hilcnin g of lh e retina in the m acular area
z o n e o f re lin a l v a s c u la r n o n p e r fu s io n in lh e m a c u la r area associated w ilh Several blo1 hem onhages (F.l Angiography
a s s o c ia te d w ilh dye le a k a g e fro m th e n e ig h b o rin g re ti­ revealed nonperfusion of lhe retina in lh e macular area and
leafage of dye from the sunoundinjj vessels IС antJ HJ. Ten
n a l v e sse ls { f i g u r e 9 .1 Ж C r £ , 1 1 . J i , 1^, a n d J . ) . 1 ' , |7 S T h e
days poslopnralively visual acu ily was Sif&O'O and lh w e was
re lin a l w b i l e n i n g a r id h e m o r r h a g e s т л у p e rs is t fo r m any
an increase in lhe area o f reLinal w bilening and hemorrhages
weeks or several m o n lh s (T ig u re 9 T 3 f). O p iic a tro p h y
111. Six monlhs laler the visual acuity was 10/200.. There were
a n d re lin a l p ig m e n ta r y c h a n g e s d e v e lo p la te r a n d m a y be aLrophic relinal antJ relinal pij’irrc-ml epithelium c h a n g K in
a c c o m p a n ie d by ru b e o s is i rid e s and h e m o rrh a g ic g la u ­ the macula.
c o m a . l h e v i s u a l p r o g n o s i s is p o o r . |-L: This woman had an exlracapsular cataract extraction
к is p ro b a b le th a t g e n ta m ic in and nol th e p reserva­ thal was complicnited Ijy vilreous loss. Four days laLer she
developed a hypopyon. A vitreous biopsy and inlravilreal
tive s is t h e p r im a r y cause o f lh e re tin a l i n f a r c t io n .Ь 4 ,] 7 '
injection of genLamrcinr vancom ycin, and dexametbasone
A lth o u g h e x p e rim e n ta lly lh e presence or absence of
were done. R a s to p ^ jtm ly she noled only bare li^ht per-
th e le n s o r v ilr e o u s does n o l change th e to xic th re s h o ld
ceplion w ilh lhe right eyre. Four months poslopera Lively her
to in je c te d n m iu o g ly c o s id e s . ih e re is concern c lin ic a lly visual acuity was t*/2Q0. Fundoscopic examination revealed
Lhal n o n to x ie doses o f a m in o g ly c o s id e s m ay be lo xic pigment cells in [he vitreous, scattered retinal hemorrhages,
if Jn je c le d in lra v itre a lly in to v itre c to m ize d eyes. whitening of the retina centrally I, and several collon-
A lth o u g h to b ra m y c in and a m ik a c in are less l o x i c th a n wool patches around the nasal aspect of the optic disc.
AngiogTHpbically I here was marked loss of Lhe retinal blood
g e n ta m ic in , b o th have p rodu ced fu n d u s fin d in g s s im i­
vessels ik and LJ.
la r l o th ose caused b y g e n l a m i c i n . T h e re lin o p a th y
has been o bse rve d m o s l fre q u e n tly fo llo w in g in lra v ilre a l
[A -l, ] *гi in' f t * Cfchild cl .bl.1 ; f- -I, ntiurlrsy ul' Ur. M .i L l h e w L) D * v i i j

in je c tio n s o f 0 . 4 m g g e n la m ic in a fte r v itr e c to m y , b u l a ls o

in s o m e cases a fle r i n je c t i o n o f 0 .1 o r 0 .2 m g doses th at
had p re v io u s ly be e n c o n s id e re d s a f e . 1 '’ P r o p h y lac tic u se a m i k a c i n . 1 ' 1 W i t h l h e a d v e n t o f s u t u r e le ss v i t r e c t o m y , s u r ­

o f s u b c o n ju n c tiv a l in je c tio n o f g e n la m ic in a fle r ro u tin e g e r y u s i n g s u b c o E i j u n c t i v a l g e n t a m i c i n is f r a u g h t w i t h th e

su rgery tvos th e second m o s l fre q u e n t cause o f m a c u la r s a m e ris k . B e c a u se o f th e fre q u e n c y a n d s e v e rity o f lh e

in fa rc tio n . 'E h e re tin o p a th y has been o bse rve d fo llo w ­ c o m p lic a tio n , C a m p o c h ia to and l j m 1 ■' recom m ended:
in g th e in a d ve rte n t in tra o c u la r in je c tio n o f to b ra m y c in {1} a b a n d o n m e n l o f p r o p h y la c tic use o f s u b c o n ju n c tiv a l
a fte r c a ta ra c t e xtra c tio n . Э ' 1 7 4 -1 7 * ]n о п е СЛИ ib is appar­ a m in o g ly c o s id e s a fte r r o u tin e surgery, a n d (2 ) a v o id a n c e
e n tly re su lte d fro m d iffu s io n of lh e s u b c o n ju n c liv a lly o f in tr a v itre a l a m in o g ly c o s id e s in (h e p r o p h y la x is o f p e n -

in je c te d drug th ro u g h th e c a la ra c t w o u n d .' " J'b e sam e e Lra lin g o c u la r i r a n m a . C e f t a z i d i m e has re p la c e d in lr a v il­

m a c u lo p a lh y has occurred a fte r in tra v itre a l in je c tio n s o f real a m ik a c in f o r ir e a lm e n l o f e n d o p h t h a l m i t i s .
 E x p e r im e n ta lly ; re lin a l to x ic ity lo g e n ta m ic in m a y o c c u r :| !4 lnlerfej-оп retinopathy
a t l e v e l s as l o w as 1 0 0 [ i g i n j e c t e d i n t o t h e v i t r e o u s . ' '' in
A —C : Bilateral nerve fiber infarcts in this 30-year-old male
th e rabbi I m o d e l D 'A m ic o e t a l . 1 '"" f o u n d la m e lla r sto r­
who was heallhv Lill he was diagnosed with nonmetaslatic
age m a te ria l in th e lip o s o m e s o f R P l: a n d m acrophages t и La net jus те1алопла 5 monlhs previously IA and EJ\ Hfi K id
a fte r in je c tio n o f 100 n g in to Lhe v itr e o u s ; d is r u p t i o n o f noticed nirld visual distortion in his left eye fur several weeks
p i g m e n t e p ith e lia l ce ll o r g a n e lle s a n d loss o f p h o t o r e c e p - w hile receiving hrgh-dose intravenous,. followed by sub-
L o r s a f t e r 4 0 0 |igr a n d f u ll- th ic k n e s s re tin a l n e c ro s is a fle r t и La net j u s , inLorferon alfa 2-b. His visual acuily was 2 0/20
in bolh eyes* Fluorescein aftgipafam a f bo(h eyes showed
SOOpg. Ih e s e fin d in g s im p lic a te th e R l 1 b. a s t h e p rim a ry
occluded елр!11лjy arierioles and capillarv nonperfusion
sile of t o x i c i t y . 111 A m in o g ly c o s id e m a a .il o p a l h y s im ila r
(Q , H e also developed a lelL cauda le nucleus infarcl re s u lt
to l h a l s e e n in h u m a n s h a s b e e n p r o d u c e d in s u b h u m a n
in^ fn a rij^hl-sidf.’d stroke and was found Lo have an ejec­
p rim a te s fo llo w in g m lra v itre a l in je c tio n o f 1 0 0 0 - 10 0 0 0 1g tion fraction of 3 0 % secondary to cardiomyopathy. Interferon
g e n ta m ic in . Ё v id e n c e su g ge sts t h a t th e r e tin a l w h i t ­ was- discontinued, the nerve fiber infarcls resolved, he recov­
e n in g a n d th e is o e le c tric e le c t r o i e t i n o g r a p h i c fin d in g s ( h a t ered com pletely from lhe stroke, and Lhe cardiac function
o c c u r w i t h i n m i n u t e s o r h o u r s o f th e in j e c t i o n a re c a u s e d improved dramatically.

b y d ire c t d a m a g e lo th e in n e r re tin a by th e d r u g b e fo re Me th amphetamine and cocaine retinopathy.

d e v e l o p m e n t o f o c c lu s io n o f th e re tin a l v a s c u la tu re . R a b b it LI and E: This 39-year-old птал w ilh a history of essential
a n d ra l n e lin a s b o t h in v i l r o a n d i n v i v o , e x p o s e d to e sc a ­ hypr rLension n c k d .y i ,:.c lo-.s nl -.ini i:i IIn- k fl ‘.'vi'. I If
l a t i n g s m a l l d o s e s o f g e n l a m ic i n , s h o w e d r e v e r s i b l e l o s s o f admitted snorting co cain e before his visual loss. Visual acu ­
b -w a ve s b u t p re se rve d a -w a v e s . I" h e r e d u c e d b -w a ve m a y ity was 20/20 right eye, and light perception only in Lhe teft
eye. Note evidence o f central retinal artery occlusion in the
be fro m m e t a b o l i c e ffe c t o n l h e b i p o l a r ce lls o r s e c o n d ­
lefl eye Lind multiple cotton-wool patches in both eyes.
a r i l y v ia e fT e c l o n g l u t a m a t e t r a n s p o r t b y th e M u l l e r ce lls.
F- H : Ih is man noted blurred vision in the lefl eye after
It is p o s s ib le th a t a m in o g ly o c o s id e s in d u c e m e ta b o lic
snorting cocaine and an argument with his wife. H e denied
change in th e in n e r n e u ro n s th at s e c o n d a rily affe c t v a s ­ trauma. The right eye was normal. Note Lhe multiple super­
c u la r p e r fu s io n . A lte rn a te ly o r in a d d itio n Lhe to n ic m e t­ ficial retinal hemorrhages, one of w hich has a white center
a b o lic e ffe c ts m a y o c c u r a t t h e v a s c u l a r e n d o t h e l i a l ce lls. (arrtiiV, Ci'i, boaL-shaped prerelinal bemalomas.. anti inlravit-
] L is to lo g y o f th e r e tin a s h o w e d d iffu s e v a c u o liz a t io n o f th e real bk>od.

nerve fib e rr g a n g lio n ce ll, and tim e r p le x ifo r m la y e r s .1 ' 1 Lid ocaine-e p i nep hri ne loxicily.
Ih e Ea lte r is a c c o m p a n i e d b y re tin a l h em orrhages, d a m ­ I—I : This 27-year-old man noted immediate pain and loss of
age l o re tin a l p e ric y te s a n d e t i d o l h e l i a l ce lls, a n d th ro m ­ vision during an anterior peribulbar injection ol lidocaine
b o s is . A p o s s ib le m e c h a n is m to e x p la in th e re lin a l v a s c u la r and epinuphi ine in lbe Lipjjei п-.isal c]uadran] in с к ф а ^ а л
o c c lu s io n w a s g r a n u lo c y tic p lu g g i n g o f Lhe re tin a l c a p illa r y Icjt]pterygium remtjval. I u iidus о к а т inal ion revealed a retinal
deiachl^ietH '.presumably ! he ancstheticl lb.il extended from
b e d .] ^
the injection sile inLo Lhe posterior fundus. Laser photoco-
In s o m e p a tie n ls a m i n o g ly c o s id e m a c u la r to x ic ity m a y
ajjulation vitas placed in the area ol lhe subrfUmal blood and
be d iffic u lt to d iffe re n tia te fr o m lh a l p r o d u c e d as a c o m ­
w ilhin hours lhe subretinal fluid had resolved. Two weeki>
p lic a tio n o f in tra n e u ra l in je c tio n d u r in g r e tro b u lb a r a n e s ­ laler Ihe optic disc was pale and its margin was blurred il).
th e s ia o r t h a t r e s u ltin g f r o m s p o n t a n e o u s o c c lu s io n o f th e There w ere fine radiating lines in the macula. Angiography
c e n tra l re tin a l a rte ry a n d v e in . T h e v itr e o u s i n f l a m m a t o r y was unremarkable except for irregular h^ perfluonescence in
c e ll re a c tio n , s h a llo w re lin a l d e ta c h m e n t, and d e la y e d the area o f laser treatment If) and staining of the optic disc
(K). Five weeks later his visual acuity was 2CV&0 and the optic
onset o f re tin a l h e m o r r h a g e s , as w e ll as th e c h a ra c te ris -
disc was pale (L).
Lic a n g i o g r a p h i c p a t t e r n a n d p ro lo n g e d re tin a l w h i t e n i n g
a s s o c ia te d w ith a m i n o g l y c o s i d e t o x i c i t y are h e l p f u l i n t h i s
I.A—
C, [ 1111г*l "iv o l IJr. Лшп U. Sinj^i ■
r e g a r d . | 7 S | 7 * ,|3 S

c o t to n -w o o l s p o ts w it h v is u a l fie ld c h a n g e s h a v e b e e n se e n ,
IN T E R F E R O N - A S S O C IA T E D th o u g h le s s fre q u e n tly , in p a tie n ts re c e ivin g in te rfe ro n

RET IN O P A T H Y ________________________ b e ta -lb fo r m u ltip le scle ro sis . T h e fu n d u s changes and

fie ld d e fe c ts re ve rse o n c e th e d r u g is d i s c o n t i n u e d . 1
P a tie n ts re c e ivin g in te rfe ro n a lfa 2 -a s u b c u la n e o u s ly or T h e s e o b s e rv a tio n s suggest lh a t p a tie n ls w it h m o d e ra te ly
in te rfe ro n a lfa 1 -b in tra v e n o u s ly (fig u re 9 .1 4 A - C ) m ay severe d ia b e tic , h y p e r te n s iv e , o r o t h e r r e t i n o p a t h y a s s o c i­
d e v e lo p m u ltip le c o tto n -w o o l is c h e m ic p a tc h e s in th e a t e d w i l h r e t i n a l c a p i l l a r y n o n p e r f u s i o n m a y b e at g r e a t e r
r e t i n a a s s o c i a t e d w i t h r e l i n a l h e m o r r h a g e s . |,J|t l h e p a t t e r n risk o f p ro g re s s io n o f th e re tin o p a th y a c id p e rm a n e nt
o f Lhe re tin o p a th y m ay s im u la te Pu rtsc h e rs re tin o p a th y v is u a l lo ss f o l l o w i n g t h e a d m i n is t r a t i o n o fla ig e a m o u n ts
a n d b e a s s o c ia te d w i t h d e cre a se d v is u a l a c u ity , 'lh e f u n d u s o f in te rfe ro n such as m ig h t h e u se d in th e tre a tm e n t o f
changes are re ve rs ib le a fte r d i s c o n l i n u i n g th e in te rfe ro n p a tie n ts w ith m a l i g n a n c i e s . - ' 01- C i r c u l a t i n g C 5 a le v e ls have-
th e ra p y. M ild d ia b e te s and s yste m ic h y p e rte n s io n w ere b e e n f o u n d to be e le v a te d in s o m e p a tie n ts d e v e lo p in g re ti­
p re s e n t in 5 0 % o f p a t i e n t s d e v e l o p i n g t h e r e t i n o p a t h y . v?l' n op a th y o n i n L e r f e r o n a l p h a ; w h e t h e r t h i s is L h e c a u s e o r
S im ila r fu n d u s changes w ith re tin a l hem orrhages and t h e r e s u l t o f t h e v a s c u l o p a t h y is u n d e t e r m i n e d . J ° J
M E T H A M P H E T A M IN E A N D 9 .1 5 C o c a i n e - in d u c e d re tin a l a n d c h o r o id a l is c h e m ia .

C O C A I N E R E T IN O P A T H Y A-F: A 50-year-okl male lost vision in his lefl eye acutely аььсь
dated wilh |bddmfnal pain and righl-sided weakness. I-!e could
I n h a la tio n o f m e t h a m p h e l a m i n e a n d c o c a in e m a y b e fo l­ bee 20/25 wilh hi-ь right eyv and could nut perceive light w ilh
his led eye. There was a coHor-wool spot in bis rrj^ht eye 4A t
l o w e d b y a c u te v is u a l lo ss i n o n e o r b o t h eyes. Th e ro u le
the left -eye bad several patches erf full-thickness retinal whiten­
o f a c q u is itio n o f th e drugs d e te rm in e s Lo an e xte n t th e
ing espciafted wilh bnoken-up blood columns in Eiolh veins and
c lin ic a l m a n ife s ta tio n s . S u b c o n ju n c tiva l p la c e m e n t of
arterioles diffusely throLJghouE the fundus (B and Df. In Lbe tem­
m e th a m p h e ta m in e re s u lts in c o n ju n c tiv itis , e p is c le r itis ., poral periphery there w ere triangles of retinal whitening fCf cor­
a n d sc le ritis. I n t r a v e n o u s a n d i n t r a n a s a l s n o r t i n g is a s s o ­ responding to fieire An'iH lie's Irianyles. An angiogram starved
c ia te d w ith a m a u ro s is fu g a x, re tin a l v a s c u litis w ith p e ri- poor blood flow Ihmugh lhe noLinnl arteries and veins and
\t-n o u 5 e xu d a tio n and v i t r i t i s . " 11'- r e L i n a l and o p tic d is c wedge-shaped areas (if increased choroidal nUorescenoe ir> the
areas intervening the while triangles yarrows), which are water­
h e m o r r h a g e s ,'' 5 m u l t ip l e c o lt o n -w o o l p a tc h e s , i^ r ls e h e r -
shed lones of lhe posterior ciliarv arteries (E-F). This palient
lik e r e t L s t o p a t h y 'r ^ and c e n lra l re tin a l arteFy o c c lu s io n
showed multiple occlusions ot both the bhorl and lorv^ posterior
(fig u re 9 .] 4 D - l l ] .Ju U lb A case o f s e v e re r e t i n a l a n d c h o ­
ciliary agones and branches Hf Ihe central relinal artery' due to a
ro id a l is c h e m ia has been seen w ith la rg e w e d g e -s h a p e d combination of vasospasn-. unci emljoli from cocaine use.
c h o ro id a l in fa rc ts c o r r e s p o n d i n g to th e A m a lr ic (r ia n g le s
P ro b a b le d e x tr o a m p h e ta m in e re tin o p a th y
in a c h r o n i c c o c a in e u s e r (I'ig u r e 9 Л . 5 С a j i d t j . ' l h e adre-
G - M : This 38-year-old Caucasian wom an with a scar in
n o m im e tic re sp o n se a n d s u d d e n in c re as e in b l o o d pres­
her rijjhl eye since childhood began nolicinjj ''translucrm 1
sure a fte r u s e o f th e s e d ru g s p r o b a b l y c o n tr ib u te to th e s e
defects^ with her lefl eye and progressive difficulty at night
r e t i n a l m a n i f e s l a t i o n s . J t ,4 ," M - j L ° R e t i n o p a t h y s i m i l a r t o l a i c over 4 years. She saw .20/100 eccentrically in her HjjM
r e t i n o p a t h y h as b e e n s e e n in o n e p a tie n t w ith in tra nasal and J0^40 in her left eye. She missed half the 3shi ha ra color
s n o rtin g o f m e t h a m p h e l a m i n e . J :i C h ro n ic c o c a in e users plates w ilh each e№ . G oldfnanh visual field revealed a cen ­
d e v e l o p 4ra s c u l a r r e m o d e l i n g w i l h in c re as e in re tin a l a rte ­ tral scoLoma in Ihfe ri^ht eye anrl full fields peripherally in
bolh eyes. Koth relinas slhowed mottling of Lhe pigment epi-
r i o l a r b r a n c h i n g a n g l e a n d v e n o u s c a l i b e r . " ' 1''
theliLim in the n'.acula and nasal Lo Lhe disc -C and H ); more
visible on [he angiogram with late sLainrng il and p. Diffuse
P R E S U M E D D E X T R O A M P H E T A M IN E reduction in autofluorescence was seen conesponding lo
Lhe relinal piemen! epi I helium change ■:К and L). An opLi-
M A C U L O P A T H Y ______________________ cal coherence tomography ibnough the left macula bhowed
disruption of lbe photoreceptors and possible thin layer of
A p a tie n t w h o w as o n d e x tr o a m p h e ta m in e ( H e x e d rin e ) fo r
subretinal fluid (M). This patient had been on dextroamphet­
I S y e a rs a l a d o s e o f i 5 m g / d a y f o r 10 years- lo ll o w e d Ь у Ш
am ine 'Doxedrine) for I fl years at a dose of 15 mg/day fur 10
m g 'd a y , d e v e lo p e d g ra d u a l d iffic u lty w ilh d a rk a d a p ta tio n
years, followed by lu mg'day for narcolepsy. An eloctroret-
a n d t r a n s lu c e n t h o le s in h e r v i s i o n . inogram showed n-ild redut.liun in rod amplitudes and cone
I le r p o s te rio r p o le showed s y m m e tric m o ttlin g al an'.pliludes a I the lower end of normal Arden ratio was J.5
th e U PE le vel in th e tw o eyes [t-'ig u r e 9 .1 S C and IE), on the righl and 2.1 on the lefl. LJenedrine was diaconlinuud
flu o re s c e in a n g io g ra m showed w in d o w d e fe c ts (J-ig u re and the patient reported improvemenl in her sympLoms al 2
m dot гаи
9 .1 5 1 and Jj. Her rod hRC was m ild ly reduced but
cone E R G w as w ith in th e ra n g e fo r her age. f O C s m ea­ LA -f, c . L iu r l t ' 1 ^ h:I LH . Ll.ivirJ j^ r r jt i a n d D t ; M i.in l.in H e e d s ' ' I K l ' | - ii i ilc:cf
I'rcriH ^ L -lin .b (' ш = a n d f t r ic f Si I 9 1 - 4 3 . W m l e r 2E>1 I .)
su red 2 .У and in th e rig h t and left e y e re s p e c tiv e ly .
D is c o n tin u a tio n o f th e m e d ic a tio n showed im p ro ve m e n t
In s ym p to m s s u b je c tiv e ly b y 2 m o n th s . She was subse­
fin d in g s in a y o u n g m a n w h o a p p a re n tly h a d an in fe c tio n
q u e n tly s w itc h e d lo a n a lte rn a te d r u g lo tre a l h e r n a r c o -
of 0.5m l Eid o c a in e -e p in e p h rin e in to lh e s u b re lin a l space
Eepsy. A m p h e t a m i n e s re le as e d o p a m in e ., and lo a le s s e r
in p re p a ra tio n fo r p te ry g iu m e xc is io n . Im m e d ia te ly a fte r
e xte n t s e ro to n in a n d e p in e p h rin e at lo w d o s e s in t h e r e t ­
th e in je c tio n h is v is u a l a c u ity w as i/2 0 0 . W h e n e xa m in e d
in a . L o n g -te r m use o f d e x tr o a m p h e ta m in e in th is p a tie n t
b y a r e t i n a l s p e c ia lis t 2 h o u r s late r, L h e i n t r a o c u l a r p r e s s u r e
m a y h a v e h a d d e l e t e r i o u s e lTe c ls o n t h e R P E .
Wnis l E r m m H g a n d t h e v i s u a l a c u i l y w a s n o l i g h t p e r c e p t i o n .
Ih e re w as m ild W h i t e n i n g o f t h e r e t i n a a t t h e site o f t h e
L 1 D O C A IN E - E P 3 N E P H R IN E in je c tio n a n d in lh e m a c u la r area. T h e re tin a w a s d e ta c h e d ,

T O X IC IT Y ______________________________ p r e s u m a b l y b y t h e i n f e c t e d lid o c a in e ^ n a s a l l y f r o m t h e s ite

o f s c le ro c h o ro id a l p e r fo r a tio n n e a r th e e q u a to r t o th e p o s ­
'ih e in a d v e rte n t in je c tio n o f lid o c a tn e in to th e in n e r eye t y p ­ te rio r p o le , i h e s u b re lin a l flu id w as n o Lo n g e r e v id e n t w h e n
i c a lly c a u s e s i m m e d i a t e (to m ia jil c l o u d i n g p u p i l l a r y d i l a t i o n ., e xa m in e d 2 d a y s l a t e r . J Ее e x p e r i e n c e d p a rtia l re c o ve ry o f
p u p illa r y p a ra ly s is , a n d p ro fo u n d v i s u a l lo s s , a ll o f w h i c h v i s i o n b u t w a s le ft W i t h a la ig e t e m p o r a l a n d c e n tra l s c o ­
u s u a lly revert t o n o r m a l w i t h i n 24 h o u r s / ' In o n e p a tie n t to m a c o rre s p o n d in g w ith (h e area o f re tin a l d e ta c h m e n t
Lh ere W a s p e rsis te n c e o f a la rg e c e n tra l s c o t o m a th a t w as a n d m i l d o p lic a Lra p h y . 'I h e n a tu re o f th e v is u a l fie ld d e fe c t
a n r ib u te d to p o s s ib le in tr a o c u la r b le e d in g , t x p e r i m e n ia lly , su ggests th a t th e s u b re lin a l lid o c a in e -e p in e p h rin e m lh e r
in tr a o c u la r lid o c a in e w a s n o l a sso c ia te d w ith e vid e n c e o f t h a n t h e t r a n s i e n t ris e i n i n t r a o c u l a r p r e s s u r e w a s r e s p o n s i b l e
p erm anent re tin a l dam age. Fig u re 9 .1 4 1 - L illu s tra te s th e fo r t h e p e r m a n e n t re tin a l v is u a l lo ss.
Q U I N I N E T O X IC IT Y 9i16 Quinine retina! toxicity,
1h ii 25-year-old wom an 5Wal3bwed 1J-15 tablets G.7-4.7f}i
f c l l o w i n g a n o v e rd o s e o f q u in in e , w h e t h e r b y a c c id e n ta l Ы quinine as a suicidal fu tu re . This w as falluw ed Liy viom-
in g e s tio n o r f r o m a tte m p ts at a b o r tio n o r su ic id e , p a tie n ts jting, E>u.i;:ing in the еагнг ап-d blindness approximately S
d e v e lo p n a u s e a , v o m it in g , h e a d a c h e , Ire m o r. tin n itu s , a n d hours laLw. tj;£irnination M '/j ЙСииъ alLur ingestion revealed
tiy p o le n s io n and n ta v b e c o m e o b lu n d e d o r even com a­ nu ligfu perceplitjn iit bolh £yes, mild lass o f rc*-LiплI transpar­
to se . W hen th e y awake w i l h in Lhe firs t 2 4 hours, th ey ency, and sIit^bL wnoiiH dimension (A). Fluorescein angiotf-
!I> 'i- :v a !'(I -r>.-i■■ i- d .4:i:■
' ^Ii.i’ii - I " ' deuils ')l
m a y b e to ta lly b lin d . lix a m i n a tio n o f th e f u n d u s at l h a l
[he choroidal fluorescence (U}. Thfrty-fi(*e hours After in^es-
tim e re ve a ls a s lig h t lo ss of re lin a l tra n sp aren cy, m ild
[юп, she noLed return | i а small island of central vision. Her
d ila tio n o f lh e re lin a l: w i n s , and n o rm a l-c a lib e r re tin a l
acuity was 2LW.20. The fturidi w ere unchanged. Five days ailer
a rteries { I'ig u r e 9 . I S A ) . 21 E 'lu o r e s c e in a n g io g ra p h y ingestion Lhere w ere fifjlicr disc pallor, narrowing of lh e neLi-
shows no a b n o rm a lity o th e r Lhan b lig h t o b s tru c tio n of nal vessels, ап-d parlial clearing al lh e relinal haiHfljeSS (L>.
th e background c h o ro id a l flu o re s c e n c e ( i'ig u r e 9 .1 6 E i) . ^■ine days afler int’eslion Ihere was further clearing of the
B le c lro re lin o g ra p h y m a y b e n o r m a l o r s h o w s lig h t changes retina and paEEor of Lhe o p !it disc (D and Eh Angiography
was normal escepl far relinal vascular narrowing (fJ- Ailer
such as s l o w i n g o f Lhe a -w a ve , tra n s ie n t in c re as e in th e
0 monlhs, visual acliltv w j h 20/1 П and 20" c f visual field
d e p th o f Lhe a - w a v e , d e c re a s e in th e b -w a ve , and lo ss o f
remained in holh eyes.
o s c illa to r y p o te n tia ls .' !" h e h O G u s u a lly s h o w s n o lig h t
r i s e . ' 14 W i t h i n s e v e r a l d a y s t h e p a t i e n t o f t e n r e c o v e r s n o r ­ Methyl alcohol octrEar toxicity,
m a l v is u a l a c u ity b u t re ta in s o n l y a s m a ll is la n d o f c e n lra l G —|: This 53-year-otd man experienced rapid lass of vision
following Ihe ingeslion of m ilh v l alcohol. Ndtfe the swelling
v is io n . T h e tiO C b e c o m e s p ro g re s s iv e ly n o r m a l. Ih e LR G
and opacification of Ihe oplrc nerve head and juxtapapi I la ry
s h o w s p ro g re s s ive lo ss o f th e b -w a ve . Recovery re tin a l
retina (C h Angiography showed minimal staining ol (he optic
t r a n s p a r e n c y , p ro g re s s iv e n a r r o w i n g o f Lh e re lin a l a rte rie s ,
nerve head И-Ei. liight weeks later ihe optic disc, was pale and
and p a llo r o f th e o p tic d isc b e g i n w i t h i n several d a y s o f the visual loss p e r i l e d 11). Angiography showed hypo fluo­
re c o v e ry o f c e n lra l v is io n (h ig u r e 9. l 6 C - f ) . V is u a l e v o k e d rescence of the o piic nerve head and evidence ot" juKlapap-
p o te n tia ls are a b n o r m a l . D ark a d a p ta tio n u s u a lly s h o w s ■!liLry atrophy of Ihcj relinal pigmenl epilhellum I that WHi
d e la y e d c o n e a d a p ta tio n and Little o r n o ro d fu n c tio n , it ргоЬаЫу presen L at Ihe lime of lh e ini Lin I photographs i com ­
pare w ilh F I:.
is p ro b a b le th a t th e in c re a s e in background c h o ro id a l
fl u o r e s c e n c e t h a l o c c u r s s o o n a ft e r t h e a c u le v i s u a l lo s s is Bisphospho nates
c a u s e d p r im a r ily b y th e re tu r n o f n o r m a l re tin a l tra n s p a r­ К and L: Sclerilis in Ihe Lefl eye within 1 w eek af receiving
e n c y. ra llie r t h a n loss o f p i g m e n t f r o n t th e Л p a tie n l ini ravenous hisphonate (ReclasL/ for sLero id-induced osteo­
w i l h a fa ile d s u ic id e a tte m p t 4 9 ye a rs p r io r u s in g q u in in e penia in a 74-year-old physician.

La b i e ls p r e s e n t e d w i l h p a llo r o f Lhe o p t ic n e rv e , h a r r o w e d [ A - 1- I ю т Hn ■■l(in h:C . : l ' | nil: li sheJ wilJi [Mjrn iis -.NJn In: nm Am ei ic.in
io u i1 1 :! u f ^ J p h l l v i iT H n lo ^ y : L t i p ^ 'r f j j h I l h u < ip iiiii-.i n :i c P i J h l l l h n :.. C o . )
re tin a ] a rte rie s and v e in s , and c o n s tric te d v is u a l fie ld s
r e s e m b lin g fie ld s s e c o n d a r y to o p e n -a n g le g l a u c o m a . T h e
K K G s h o w e d re d u c e d a m p litu d e s a n d in c re a s e d la te n c y f o r
b o t h s c o t o p i c a n d p h o l o p i c f u n c t i o n . " ' 1"
LR G done on c h ild re n w ith cerebral m a la ria fro m a c u te s la g e s o f th e d ise a se s u g g e s t lh a t v a s c u la r c h a n g e s
f J r a j r i q r f j u m ju lc ip tin trn r e c e i v i n g t h e r a p e u t i c d o s e s o f q u i ­ p la y little ro le in c a u s in g Lhe re tin a l dam age. Lhe pro­
n in e s h o w s a re ve rs ib le d ecrea se in lh e a -w a v e a m p lit u d e g re s s iv e n a r r o w i n g o f th e r e t m a l a r te r ia l tree Lhat u s u a lly
o f m a x im a l p h o lo re c e p lo r re sp o n se and cone response d o e s n o t b e g in u n t il a fte r th e p a tie n L h a s re c o ve re d ce n tra l
f r o m t h e t i m e o f q u i n i n e i n f u s i o n . " 1'' ' 1' v is io n is p r o b a b l y c a u s e d b y a t r o p h y o f Lhe in n e r re tin a l
In a n im a ls w i l h e x p e r im e n ta lly in d u c e d q u i n i n e re tin a l la y e rs as w e l t a s in c re a s e d o x y g e n t e n s i o n r e l a t e d t o g r e a te r
to xic ity h is to p a th o lo g ic e x a m in a tio n o f th e e a rly c h a n g e s d i f f u s i o n o f o x y g e n f r o m th e c h o r o i d d u e t o lo ss o f p h o t o ­
s h o w s e v i d e n c e o f p h o t o r e c e p t o r c e l l as w e l l as g a n g l i o n re c e p to rs . 'lb u s , th e re is n o ra tio n a le fo r re tin a l v a s c u la r
cell a lt e r a t io n s .'''1 " ^ In la te r stages o f th e d is e a s e in d ila t o r s in th e tre a tm e n t o f q u i n i n e to xic ity . L o w e r in g of
h u m a n s , h is to p a th o lo g ic e x a m in a tio n s h o w s lo ss o f g a n ­ th e p la s m a le ve l o f q u in in e w ith re p e a te d oral a d m in is -
g l i o n ce lls, n e r v e f ib e r la y e r, a n d p h o t o r e c e p t o r s . f rat i o n o f a c t i v a t e d c h a r c o a l th e o re tic a lly m a y be b e n e fi­
P u p i l l a r y a b n o r m a l i t i e s Lh a t m a y b e p e r m a n e n t in th es e c ia l.^ l h e r e is, h o w e v e r , n o t r e a t m e n t o f p r o v e n v a l u e .
p a tie n ts in c lu d e poor re a c tio n lo lig h t, Io n ic p u p illa ry Q u i n i n e to x ic ity ty p ic a lly o c c u rs w i t h o ra l d o s e s g re a te r
re a c tio n , ve rm ifo rm p u p illa ry m o tio n , and d e n e rv a tio n i h a n 4 g, b u t t h e r e Lia v e b e e n m a n y case r e p o r t s o f t o x i c i t y
s u p e r s e n s i l i v i t y . Jl ■'■- ] 6 2 2Л w ith s m a lle r d o se s, lh e re co m m e n d e d d a ily th e ra p e u tic
The n o r m a l c a l ib e r o f t h e re lin a l a rte rie s a n d th e n o r ­ d o s e is n o m o r e i h a n 2 g . a c i d L h e f a t a l o r a l d o s e f o r a d u l t s
m a l re tin a ] a n d c h o r o id a l c ir c u la tio n Lim e seen d u r i n g th e is a p p r o x i m a t e l y E l g .
Q tim inC Ttt.VrL-jflf 7 39
M E T H Y L A L C O H O L T O X IC IT Y 4 ,17 D r u g -in d u c e d c y s to id m a c u la r e d e m a .

W ith in 1Й -4 3 Eio u rs o f th e i n g e s t L o n o f" m e t h y l a lc o h o l., G lu c o p h a g e

w h ic h is m e t a b o l i z e d lo fo rm a ld e h y d e and fo rm ic a c id , Л -F: This 48-year-old k'fie 2 diabetic with ™ blifeialLve dia-
p a tie n ts m ay e xp e rie n c e s ym p to m s ra n g in g fro m sp o ts heLrt relinopalhy had no macular edema and a visual acu ­
ity of 20/25 - in his lefL «ye lAl. He* rmurnttl cornplairing
b e fo re lh e eyes lo c o m p le te b li n d n e s s .D im i n u t i o n
ot ftucLualrng vihitm 4 rrmnltih later when his vision had
o f p u p illa ry re a c tio n to lig h t m a y o c c u r itt p a t i e n t s w i t h
d t t r e u e d Lu 20/40 due to cysloEd m acular edema (ft—E>.
im p a ire d v is u a l a c u ity as w e ll as in som e p a tie n ts w ith
He was a Isci noted Lo have evidence faf fluid nelenlion ^vilh
n o r m a l a c u ily . 1 Ъ е d e g re e o f p u p i ll a r y lig h t re fle x i m p a i r ­ pedal edcmia. H e was on ^lu-copha^e in add i I Lon lo insulir.
m ent is o f c o n s i d e r a b l e p ro g n o s tic s ig tiific a n e e . Lna t i e n t s Clucophage wjls discontinued and he returned 5 weeks laler
w i t h d ila te d , fix e d p u p ils u s u a lly d ie o r s u ffe r severe vis u a l wiLh return Ы| vision Lo 20/25 and complete resolution of Ihe
dam age. l :u n d o s c o p i c e x a m in at i o n shows h y p e re m ia o f cystoid edema on optical coherence tomography lO C T ) iFf
and siynificanl impfovc.inc.4iL i:n !iiн pedal edema.
th e o p t ic d is c , w h iL is h s tria te d e d e m a ol" t h e d i s c m a r g i n s
and a lo n g th e course o f th e m a jo r re tin a l v e sse ls, and P a c lila x e l.
e n g o r g e m e n t o f t h e r e tin a l v e in s (I'ig u r e 9 . 1 6 C ] P a tie n ts G - L : A trf3-year-old wom an w ilh bilateral gradual decrease
w ho s u rv iv e and s u s ta in severe vis u a t dam age d e v e lo p in vision over 6 months Lo 2G/30 in Ihe righl eye and 2 0 /7 0
o p tic a tro p h y in a p p ro x im a te ly 1-2 m o n th s (fig u re in Lhe lefl eye. KoLh macula showctd cystoid swelling more
Visible on lhe O C T images (C-|). An angiogram showed ло
9 .1 6 1 ) . A dense c e c o c e n lra l sc o to m a , o fte n s p a rin g c e n ­
dye leakage in either fovea (K and t.J. The patient was receiv­
t r a l f i x a t i o n , is t h e m o s t f r e q u e n t f i e l d d e fe c t. N e r v e fib e r
ing Abfaxirte (albumin-hound pacliLaxel nanoparticlre- for
b u n d le d e fe c ts and p e rip h e ra l fie ld c o n s tric tio n d e v e lo p
meLa-staLic bread cancc.1 , Lhe cause of cyslic rraculopathy.
fre q u e n tly a n d b lin d n e s s m a y occu r. EiR C nib n o r m a l i l i e s
[Ci-L, C4iu rlL'iy ul 3>r LJ-.t , nrvVHiinljijr^.l
in v o l v i n g th e a - a n d b -iv a v e s occu r. -
lixperimental findings in rhesus monkeys suggest that
Lhe primary lesion tn methyl alcohol poisoning is dis­
ruption of axoplasmic How just at or behind the lamina
c r i b r o s a . ' it is postulated that Loxic metabolic break­ coniunclivilis, an Leri or uveitis, episcleritis,, anterior and
down products o f methanol exert adverse effects on cyto­ posterior sderitis and acute retinal pigment epitheli-
chrome oxidase and other oxidative enzymes, which i L i s . ^ lhe onsel o f ocular symptoms occurs Within
causes spelling o f the oligodendroglial cells in the retro la­ 24-43 houfs of infusion. Ail cases of iridocyrclitis respond
minar optic nerve. Ibis resulLs in axonal compression, axo­ lo topical steroids and the sderitis to oral steroids, lhe one
plasmic flow stasis, and optic disc edema."''' case o f retinal pigment epitheliiLis resolved spontaneously.
IJe ce nl re p o rts of e xp e rim e n ta l m e th a n o l to xic ity in O r a l p re p a ra tio n s a le n d ro n a te , ris e d ro n a te , a n d e tid r o ­
rats a n d e l e c l r o p h y s i o l o g t c a n d h i s t o p a t h o l o g i c s t u d ie s in n a te have been a s s o c ia te d W ith b lu rre d v i s i o n , e y e p a in .,
a hum an w ith m e th a n o l to xic ity h ave d e m o n s tra te d e vi­ c o n iu n c liv ilis . u ve itis , and sc le rilis [Fig u re 9 .I 6 K ) Ih e
d e n c e lh a l th e re tin a l re ce p to rs a n d R P E a re a ffe c te d . ■
D ] ,2 3 J o n s e t o f s y m p t o m s o c c u rs 2 d a ys to 2 w e e k s a fte r s ta rtin g
lh e a b s o rp tio n , d is trib u tio n , a n d m e ta b o lis m o f m e th a ­ th e ra p y. T h e y are s e lf-lim ite d i f m i l d , a n d m o d e r a t e cases
n o l a n d e t h a n o l are s im ila r S in c e e t h a n o l has a 10 0 -fo Jd r e s p o n d lo to p ic a l s te ro id s .
g re a te r a ffin ity fo r a lc o h o l d e h y d r o g e n a s e th a n m e t h a n o l ,
tre a tm e n t c o n s is ts o f e a r ly a d m in is t r a t io n o f e th a n o l and
c o rre c tio Et o f m e t a b o lic a c id o s is .
PACLETAXEL T O X IC IT Y _______________
P a c lila xe l and d o c e la x e l are a n tim ic ro lu b u le ag en ts th a t

B IS P H O S P H O N A T E S in h ib it m ito s is and are u s e d as c h e m o t h e r a p e u t i c ag en ts

f o r b r e a s t a n d l u n g c a r c i n o m a . N o n lea k i n g c y s t o i d m a c u ­
Kisphospho nates used Lo treat osteoporosis inhibit l a r e d e m a t h a t is r e v e r s i b l e o n d i s c o n t i n u a t i o n o f t h e d r u g
bone resorption by binding to hydroxyapatile ciys- is s e e n w i t h th e p r o t e in - b o u n d f o r m o f p a c lila x e l [E 'ig u r e
Lais and inhibit their dissolution, [ntravenous prepara­ 9 .1 7 С Lo O n e p a tie n t e xp e rie n c e d p h o to p s ia s
tions pamidronate disodium and xoledronic acid cause a n d v i s u a l l i e l d d e f e c t s . 1 ,!
IM A T JN IB M E S Y LA T E (G L E E V E C ) IS Venlafaxine (EffexorHnduced cystoid macular
edema fCME),
T O X IC IT Y
A - H : This- 48-year-ofd wom an showed worsen i ng o f her situ-
Im a tin ib m e s y la te used in th e tre a tm e n t of le u k e m ia aliona! depression and developed bilateral blurrud vision
pauses flu id re te n tio n and c o n ju n c tiv a l and p e rio rb ita l over 2 monllis following a nvviI<.It Щ her anljdupressanl from
Lexabffr to V En lafaj$ & (ЁН ём х XI£i. AlLe* 1 monLhs being
e d e m a in л! m o s t 3 0 % o f p a tie n ts . C y s to id m a c u la r e d e m a
on lbe medication venlat'axine was t handed to W ellhulriii,
w ith o r w it h o u t s u b re tin a l flu id lh a t is r e v e r s i b l e if lh e
which helped her depression. Her vision remained affec led
d rug is d is c o n tin u e d e a rly has been re p o rte d in th re e and she was found to have bilateral cystoid тасиГаг ed ^iia,
c a s e s .■
i43- i * * jh e m e c h a n is m is s t i l l s p e c u l a t i v e ] f ste re o Ilicit on angiography shew ed accum ulation of dye via lhe
flu o re s c e in a n g io g ra p h y d e m o n s tra te s in tra re tin a l flu id relinal pLgmemj epithelium and visible on oiMical coherence
a c c u m u la tio n fro m RPB d y s fu n c tio n oral a c e ta zo la m id e (вт&дгэрНу 'A-H). The C.Mt responded lo hi la ter a I intravil-
m a y b e u s e fu l in tr e a tin g t h e c y s to id e d e m a .
real trian'.rinalono (4 m.g. but re tim e d in 2 -monlhк w hen
she a Iso developed bilalera! posterior subcapsular (.alniacls
cird persislenl elevated intraocular prmsures lhal required
G L IT A Z O N E T O X IC IT Y _______________ bilateral trabeculectomies. Topical Trud E-orto did nol help
the C M E. Since Lhe dye acepmtflated from incon jpeLence of
C l t l a z o n e s ( m s i g L i t a z o n e a n d p i o g l i t a z o n e ) u s e d to r e d u c e lhe piemen I epil helium, she; was stark'd on oral aee]<tJ!ol-
in s u lin re s is ta n c e in t y p e 2 d ia b e tic s c a u s e flu id r e t e n t io n nn_jide R i 2 5 0 m g :hree limes a day. Гhe t'Vlb responded and
and pedal edem a in 4—7 ° о o f p a tie n ts w h e n used л1опе resolvtid over 2 months IG and Hi. She was slowly tapered
and u p lo 15 % when used w ilh i n s u l i n . 2-1 s f h e s e p a t i e n t s off lhe acelazolam ide over 4 months -and L,\lL did not recur.

s h o w p e d a l e d e m a a n d ra p id w e ig h t g a in , w h ic h i m p r o w s Dehyd ra tion/marathon re tin opat hy.

a fte r d i s c o n t i n u i n g th e d r u g . C y s t o id m a c u la r e d e m a sec­ I- К : This 30-year-old Asian-lndian orthopedic resident
o n d a r y t o d iffu s e le a k a g e o c c u rs in s o m e o f th es e p a tie n ls aw oke w ilh decreased vision in the riulil eve. He had run
and is re fra c to ry to la s e r t r e a t m e n t and d i u r e t i c s . - ' -" 1" 4 " 20 mi3es a day and half before. H e was a -*JD myope and
D is c o n tin u a tio n o f th e m e d ic a tio n h e lp s if done e a rly. was otherwise heallhy. Visual ac uil\ was counting fin­
gers at 1.2 meter (4 feel I in the right eye and 20/25 in the
S im ila r o c c u rre n c e o f c ysto id m a c u l a r e d e m a in a typ e 2
lefl eye. H e hud а central scotoma on lhe Coldm ann visual
d ia b e tic p a tie n t o n m e tfo rm in w h ic h re s o lve d w ith in 6
field: there w ere several coLLon-wool spots, dal-blot hemor­
weeks fo llo w in g d is c o n tin u a tio n of m e tfo rm in is illu s ­
rhages, and cllici-relinal artery occlusion o r lhe rijjhl (I and
tra te d in f ig u r e 3 . 1 7 A - K 1.1. Fluorescein anyioyram showed blowing ol (low lh rough
lhe cilio-retinal arterv on lliis hjcJ-l* IL '. Probable risk factors
included homo^ygosiLy lor M TH FH А129ЙС mulation and
N I C O T I N I C A C ID M A C U L O P A T H Y recent dehydration, al of whit h caused him to develop lhe
cenlral retinal veirV'ciItary retinal artery occlusion. A w eek
See C h a p t e r 6.
Iate*, his visual acuity improved to 20/20. H e had a small
inferotempora! relative para cenlral scotoma and ended up
E P IN E P H R IN E A N D running ih e tlh ica g o marathon .1 w e e is laler.

P R O S T A G L A N D IN A N A L O G - High-altitude retinopathy
IN D U C E D C Y S T O ID M A C U L A R UN A 2 (>y ear-old m ale noted blurring ot his rij’ hl eye
vision 3 nights into his clim b ot Mount MuzLaj’ala fat 20 000
EDEM A feel (Й09& meters^). The highest point is at 24 7 5 7 feet \75A b
metersi. The picture was laken 10 days later when his vision
t o p ic a l e p in e p h rin e d ro p s a n d p ro s ta g la n d in a n a lo g s such was recorded at 2Q/HO in the righl and 20^20 in 1he left eye.
as l . i t a n o p r o s t , t r a v a p r o s t , a n d h i m e l o p r o s l c a n c a u s e a n g i o - Hu had two птлсиЗнг nrerelinal hemorrhages on the righl
g ra p h ic a lly e v id e n t c y s to id m a c u la r e d e m a , o fte n revere and few intraretinal hen'jorrhajjes in the left eye <L and Ml>.
i b l e o n d is c o n tin u a tio n o f th e m e d ic a tio n . Flurirescein ani^iojjram only showud blocked fluorescence
from Ihe hemcjrrbiage iN:. His hemorrhages cleared and
vision returned to 20/20 in both eyes.
V E N L A F A X IN E I k. njurLcsy uf Dr M .ilhcw Г1
,l.iLf LimhtT .ind J>r. Kiri. HhLiiti. L-N.
c t J t j r t e i Y г»Г I J r . H o n A i S « i i T j n . ■
V e n la fa x in e [Effe xo r), an a n tip s y c h o tic dru g, is r e p o r t e d
to cause b le p b a re d e m a . Jh e a u th o r has seen a p a tie n L
w ho d e v e lo p e d b ila te ra l c ysto id m a c u la r edem a (l-'ig u re
9 . 1 £ A . IV h , a n d h ) a s s o c i a t e d w i l h o t h e r s y s t e m i c s i g n s o f llu o re s c e in a n g io g ra p h y d e m o n s tra te d le a k a g e o f d y e at
in to le ra n c e to ve n ta fa \in e . ih e edem a p e rs is te d in sp ile th e R P L ( } ig u r e 3 .1 S C a n d P ) p r o n tp tin g tre a tm e n t w ith
o f d is c o n tin u a tio n o f th e drug, and recu rred 2 m o n th s oral a c e ta zo !a m id e fo r 3 m o n t h s r w h ic h re s u lte d in r e s o lu ­
fo llo w in g b ila te ra l in tra v itre a l tria m c in a lo n e in je c tio n s . t i o n o f c y s l o i d m a c u l a r e d e m a ( l ;ig u r e 5 .1 S C a n d H ) .
M A R A T H O N / D E M Y D RATI O N 19 Tacrolimus microangEopathy.

R E T IN O P A T H Y A - H : Th is 2-t-year-cikl east 1пс.Мч"эп man was seen Ъ weeki;

potl rrmal t r a n s p l a n t f u r cbrun i c ^lomcffuloncphriras w i l l :
M a ra th o n ru n ners can present w ith v e n o u s d ila tio n and oomplamLsi o f blurred vision m TijjhL E y i of 2 w eeks' dura­
t io n . H is S^sfemlt i im m u n o H u p p r u b b a n L Ih-Lj rs_|>v ir>cIli:c led
re tin a ] h e m o r r h a g e s re s e m b lin g c e n Lra l re tin a l v e in o c c lu ­
tacrolimus, m ycophenolale m o f e t i l r and corticosteroid. H i s
s io n (fig u re 9 .lt i [ - K ) . ih e fin d in g s u s u a lly im p r o v e w ith
b c H l - C D r r t K l u d visual acuily was 20/400 m t h e T i^ h t a n d
re s o lu tio n pf hem orrhages and re s to ra tio n of venous
20/30 m lbLL left eye. Tbe fnatflla of bolli eytb showed isch­
c a lib e r W ith lim e . A concurrent cili o r d i n a l a rtery o c c lu ­ em ic relinal whitening :A and №.. Tbe foveal avascular йопё
s io n can o ccu r d u e to c o m p re s s io n fro m t h e v e in (l-ig u re was irregularly enlarged with -sudden lermi nation of arte-
Э .Ш - К ). rioies; and fflild staining o f Ihe capillary walls in lale-phase
I x e r c i s e in c r e a s e s p la te Lei a c t i v a t i o n a n d o t h e r c l o t t i n g angiogram HCl—F >. H is hemoglobin was lO g 1 ^ . Tacrolimus
was discontinued and the dose erf oral corticoslercudh was
fa c to rs . 'I h is in c re a s e in c l o t t i n g fa c to rs in tb e c o a g u l a t i o n
increased after cun^ullation with his nephrologist, iiix
cascade is u s u a l l y b a la n c e d by a c tiv a tio n o f fib rin o ly s is
monLhs Inler, his visual acuilv had improved to 2 (1/BO in lbe
c a s c a d e as w e l l , in t h o s e i n d i v i d u a l s W i t h a p r e d i s p o s i t i o n rigbt and 20/60 in lbe left eye w ilh resolution ol o pacifica­
to d o t t i n g o r w ith o th e r ih ro m b o g e n ic risk fa c to rs , a lo n g tion in both e\i!H !G and M:.
w ilh a c c o m p a n y i n g d e h y d r a t i o n , se v e re e xe rc is e m a y d i s ­
i . A - l l, t n u rr-L-v f o l D r . V i s h j t l G u p b . i n d 3>г. Л п ш : ! G u f lj f c i -]
ru p t th e b a la n c e b e tw e e n c o a g u la tio n and fib rin o ly s is ,
p l a c i n g t h e m a t r i s k f o r t h r o m b o s i s . 2^ 3
M o u n t b verest ( - - 5 0 0 0 m or 16 000 fe e l) w ere fo u n d lo
t h e o l o g i c a l r e s p o n s e Lo e x e rc is e w a s c o m p a r e d t o c o n ­
h a v e v a r io u s d e g re e s o f re tin a l hem orrhages and d ila te d
tro l s u b je c ts in a p a l ie n t w h o d e v e lo p e d a c e n tra l re tin a )
le Lin a J ve in s . M o s t w ere a s y m p to m a tic or m ild ly s y m p -
ve in o c c lu s io n fo llo w in g a m a ra lh o n . D u rin g a stand ard ­
l o m a l i c . 25' A 3 3 -y e a r-o ld o th e rw is e h e a lth y m a le d e v e l­
is e d s u b m a x i m a l e xe rc is e le s t, th e in c re a s e in b l o o d v is c o s ­
o p e d u n ila te ra l a n te r io r is c h e m ic o p tic n e u r o p a t h y w h ile
ity and h e m a to c r it ( - 2 5 % ) e xc e e d e d th e c o n tr o l
liv in g o n Lhe S ia c h e n g la c ie r ( 5 4 7 2 m e te rs (17 353 fe e t)
ra n g e a n d r e d ce ll a g g r e g a tio n (M yre n n e -+ 47Ч Ъ ) a n d d is ­
above sea ! e v e l ) . J ',fl A b n o r m a l a u to re g u la tio n m ay have
a g g re g a tio n th re s h o ld s (A ffib io + 3 7% } w ere s trik in g ly
c o n trib u te d Lo th e p e rs is te n t v a s o s p a s m at h ig h a llitu d e .
d iffe r e n t f r o m c o n tr o ls . A ro le f o r h e m o r h e o lo g ic a l a lte ra ­
H y p o x i a causes d e c o m p e n s a tio n o f th e v a s c u la r e n d o t h e ­
tio n s d u r in g e xe rc is e i n t h e p a th o g e n e s is o f a m a r a t h o n -
liu m , w h ic h m a y a c c o u n t fo r th e re tin a l h e m o r r h a g e s . In
i n d u c e d r e t i n a l t h r o m b o s i s is p l a u s i b l e a n d s u c h c h a n g e s
g e n e r a l t h e v i s u a l p r o g n o s i s is g o o d .
m a y p e r s i s t a f t e r t h e e v e n t . ' 411' ' '

H IG H - A L T IT U D E R E T IN O P A T H Y C A R B O N M O N O X ID E
R E T IN O P A T H Y
O th e rw is e h e a lth y in d iv id u a ls f r - 5 6 h o u r s a fte r a s c e n d in g
t o h e i g h t s u s l i <:. I ! y o v e r 5 0 0 0 m m a y d e v e lo p re tin a l h e m - S u p e rfic ia l re tin a l h e m o r r h a g e s in a p a tte rn s i m i l a r Lo t h a t
oiThagesr p a p ille d e m a , d ila te d re tin a l ve sse ls* e n lo p s ia s , s e e n in l f c r e o n rs s y n d r o m e { s e e H g u r e S . 0 7 ) a n d i n m o u n ­
a n d s e le c tiv e loss o f c o l o r v i s i o n . - ^ 1' - - ^ T h e r e t i n a l h e m o r ­ ta in c lim b e r s e x p o s e d to h i g h a lt it u d e s (see e a r lie r s e c t io n )
r h a g e s a r e s u p e r f i c i a l , are w i d e l y s c a tt e r e d , a n d fre q u e n tly m a y o c c u r In p a tie n ts w ith a c u te o r s u b a c u te e x p o s u r e to
s p a re th e m a c u l a (I'ig u r e 9. I S L - N ) . T h e s e p a L ie n ts m a y o r carbon m o n o x i d e . " " - 1" 1'' Ih e xe m ay o c c u r in a ss o c ia tio n
m ay not h a v e s y s te m ic s y m p t o m s o f m o u n ta in sic k ness, w ilh p a p ille d e m a and re tin a l venous engorgem ent and
in c lu d in g headache, in s o m n ia , a n o re x ia , and o c c a s io n ­ to rtu o s ity . It i s u n c e r t a i n w h e t h e r d i r e c t h y p o x i c daEnage
a lly p u l m o n a r y e d e m a , c e re b ra l e d e m a , a n d c o m a . O c u l a r l o th e v a s c u la r e n d o t h e l iu m o f th e o p tic n e rv e a n d re tin a
and s y s te m ic b lo o d pressures in c re a s e in p a tie n ls w ith o r c o m p r e s s io n o f tb e r e lin a l v e n o u s d ra in a g e a s s o c ia te d
m o u n t a i n s ic k n e s s . S i m i l a r re lin a l fin d in g s o f re tin a l hem­ w ith cerebral a n d o p tic nerve edem a, o r a c o m b in a tio n
orrhages and d ila te d re tin a l v e in s h a v e been seen occa­ o f b o th , is r e s p o n s i b l e fo r lh e fu n d u s changes. S m o k e rs
s io n a lly a fte r lo n g -h a u l c o m m e rc ia l flig h ts over 2500m are m o r e v u l n e r a b l e lo e n v iro n m e n ta l carbon m o n o xid e
(8 0 0 0 f e e t ) . - ' "■ ' I h i r t y - l h r e e o f 4 0 c l i m b e r s w h o a s c e n d e d a f f e c t i n g t h e i r d a r k a d a p t a t i o n a n d E i g h t s e n s i t i v i t y . - ' '■
IN D O C Y A N IN E G R E E N T O X IC IT Y 9.2(1 Tacrotim ti s m iс roangi opa thy

A—K: Tliis 43-year-old Indian m ale presented with sudden

Ih e use o f in d o c y a n in e gFeen dye d u rin g c h ro m o v it­ pro^nes-мve d ecreet? in vision in bolh lor 4 weeks. He
re c to m y lo s ta in th e in te rn a l lim itin g m em brane has had receive^ л live related гслчь] flJIogiafl f) weeks previously.
in i p r o v e d th e success rate of m пси ta r h o le c lo s u re . He was on l«(.Tt)liniLii ^nifl tw ice i\ djiy,. m yajp henolate
H d W e v E | v a rio u s in sta n c e s of re tin a l to xic ity have been mofclil 1 ^ twice д day and praHnhfal-ane E5m^ o n ce dailv.
n o te d . The p o s tu la le d m e c h a n is m s in c lu d e d ire c t b io ­ He was also on Eilcod pressure medication and his blood
pressure read 1.JCVSO rr.mH^. His visual acuity w asuount fin­
c h e m ic a l to xic ity to th e n eu ral re tin a l ce lls and RPE,
gers at 0.5 meler. Both macuJa showed whilEming with reti­
o s m o l a r i t y e ffe c t o n th e v itr e o r e fin a l in te rfa c e , m e c h a n ic a l
nal ЕттоггИп^еъ. An a r { jj c ^ a ] | fchowSd macular infaffillttfi
c le a v a g e e ffe c t t o t h e in n e r l i m i t i n g m e m b F a n e / i n n e r re ti­
with occlusion of Lhe perrloveal arterioles. H e showed no
n a l s u r f , i c e a n d l i g h t - i n d u c e d i n j u r y ^ 53 2Ji| T h e d i r e c t d a m ­ evidence о I Lhrombocytopen ia, renal failure, or hemolysis.
age to , a n d in d u c tio n o f a p o p to s is o f. n e u ro re tin a l and Four monlhs later Ihe relink I whitening had mostly resolved
ftPE c e l l s a p p e a r lo b e d o s e -d e p e n d e n t. In d o c y a n in e green find iiy El months his vision had stabilized at 2 iV 2 0 0 in bolh
a b s o rp tio n o f lig h t is in ih e n e a r-in fra re d ra n g je (7B 0 -
eyes. O ptical coherence tomography of both macula showed
sthidit-fifce (.rivitk'H Without я щ тГ г с а т overall thickcnin^,
830nm ) and in d u c e s p h o to o x id a tio n typ e I [in c re a s e d
signifying loss o f rrf ina I suEistance.
lo c a l t e m p e r a t u r e o f tis s u e } a n d p h o to -o x id a tio n typ e [[
[A —I f , с п и rltis y u l a>r. W . h .ili 'L ib |:l.n a n d I7 i A m u J G ij p l . i . l
( p h o L o d y n a m ic e f f e c t s ) . J 1 - )f’
B io c h e m ic a l changes in th e in n e r lim itin g m em brane
w ith in c re a s e d s t i ffe n i n g h a s a ls o b e e n n o t e d .2 1' T o m in i­
drug or is a r o u t i n e n o n a rte ritic a n te rio r is c h e m ic o p tic
m iz e to xic ity , a lo w c o n c e n tra tio n , s h o rt d u r a tio n , a n d lo w
n e u r o p a t h y o c c u r r i n g in th e g r o u p o f p a t i e n t s w h o are p r e ­
illu m i n a t io n are r e c o m m e n d e d /
d is p o s e d to th is c o m p lic a tio n . " 1 T h e c o m e a l d e p o s its m a y
re s u lt in b lu e - g r e e n rin g £ o r c o lo r e d h a lo s a r o u n d lig h ts . A
T A C R O L IM U S T O X IC IT Y _____________ m a c u l o p a t h y a tt r ib u t e d lo a c c u m u l a t io n o f th e d r u g in th e

ih ro m b o tic m i c r o a n g i o p a t h y o f v a r i o u s o r g a n s is a s i d e - K PL h a s b e e n d e s c r ib e d ; h o w e v e r t h e cases w e r e n o t w e ll
d o c u m e n t e d a n d m a y n o t b e re la te d to a in ia d a r o n e .''^ " 1
e ffe c t o f ta c ro lim u s ( ] :K 5 0 G ) and pre se n ts as a re tin a l
in fa rc t w ith c o tto n -w o o I s p o ts and re tin a l h e m orrh ag es
in th e eye [fig u re s 9 .1 9 A a n d К a n d 9 .2 0 Л a n d H ) . J ,:" T h e S IL D E N A F IL (V IA G R A )
u n d e rly in g m e c h a n is m is th ro m b o tic th ro m b o c yto p e ­
I h e c o m m o n e s t sid e -e ffe c t o f V ia g ra is a t r a n s i e n t b lu is h
n ia a n d h e m o ly s is , w h ic h re q u ire d is c o n tin u a tio n o f th e
d ru g, p la s m a p h e re s is , a n d fre s h fro ze n p la s m a as r e s c u e , d is c o lo ra tio n o f v is io n a n d im p a ire d b lu e /g re e n d is c r im i­
n a tio n . lie ro u s re tin a l d e ta c h m e n ts s im u la lin g id io p a th ic
lin d o th e lia l s w e llin g a n d in tra lu m in a l fib rin are seen in
th e g lo m e ru li on k id n e y b io p s y M u o re s re in a n g io g ra m c e n tra l s e ro u s c h o r i o r e t i n o p a t h y h a v e b e e n s e e n in p a tie n ts
ta k in g s ild e n a fil fo r e re c tile d y s f u n c t io n .J:' it is a
re ve a ls o c c lu d e d m a c u la r v e sse ls [E: ig u r e s and
9 .2 0 C - H ) . S c liisis-tik e changes are s o m e tim e s seen due c y c lic g u a n o s in e m o n o p h o s p h a te -s p e c ific p h o s p h o d ie s ­
te ra s e t y p e 5 I n h i b i t o r , w h i c h is a p o t e n t v a s o d i l a t o r t h a t
to lo ss o f re tin a l tissu e fro m in fa rc tio n (Fig u re 9 .2 0 H
and E) Yhe m i c r o a n g i o p a t h y u s u a l l y o c c u r s w i t h i n a f e w in cre ases c h o r o i d a l th ic k n e s s b y 3 0 % b y in c re a s in g c h o r o i ­
dal b lo o d flo w b y 2 0 - З О % . " &* C h o r o i d a l e n g o r g e m e n t as
d a y s p o s t t r a n s p l a n t a n d is s e e n p o s t s o l i d o r ^ a n a n d b o n e
m a r r o w t r a n s p l a n t . S i m i l a r m i c r o a n g i o p a t h y es s e e n W i t h a n i d io s y n c r a t ic e ffe c t m a y b e th e u n d e r l y i n g m e c h a n is m
o f e x u d a tiv e re tin a l d e ta c h m e n t : In m o s t p a tie n ts th e
ty c lo s p o rin e , s iro lim u s , and s y s te m ic a n ti v a s c u la r endo­
th e lia l g r o w th fa c to r th e r a p y (V K C E -) w it h b e v a c iz u m a b . s e ro u s d e t a c h m e n t re s o lv e d o n d is c o n t in u a t io n o f th e d r u g
[d e c h a lle n g e ) a n d re c u rre d in a fe w o n B ^ a l l e n g e . ^ 0"3' ^
Is c h e m ic o p tic n e u ro p a th y, branch re tin a l a rte ry o c c lu ­
A M I O D A R O N E O P T IC s io n , a n d a n a c u te t h ir d -n e r v e p a ls y h a v e a ls o b e e n s e e n ;
N E U R O P A T H Y ________________________ h o w e v e r th e s e m a y b e re la te d to v a s c u la r c o m p r o m i s e in
p a t i e n t s a l r e a d y p r e d i s p o s e d t o v a s c u l a r a c c i d e n t s . J H ) - J , ' :i
P a tie n ts re c e ivin g a m io d a ro n e , an a n tia rrh y th m ic d ru g ,
m a y d e v e l o p v e r l i c i ll a L e k e r a t o p a t h y , t r e m o r , a ta x ia ., p u l m o ­
nary fib ro s is , a n d o c c a s io n a lly v is u a l lo ss a s s o c ia te d w i t h
C O R T IC O S T E R O ID -
o p tic d isc s w e llin g a n d h em orrh ages. I'h e s e c h a n g e s m ay A S S O C IA T E D C E N T R A L S E R O U S
be fo llo w e d b y o p tic a tro p h y a n d n a r r o w in g o f th e re tin a l
C H O R IO R E T IN O P A T H Y
a r t e r i e s i n s o m e p a t i e n t s . ^ ' 0" 3^ i t is u n c e r t a i n w h e t h e r o r
n o t t h i s o p t i c n e u r o p a t h y is a p e c u l i a r c o m p l i c a t i o n o f t h e See C h a p te r 3.
R E T IN O ID S V IG A B A T R JN
A fe w p a tie n ts c n is o tre tin o in th e r a p y fo F a cne c o m p la in V ig a b a trin is a g a m m a -a m in o b u ty ric a c id tra n s a m in a s e
o f p o o r n ig h t v is io n and d iffic u lty vrfth d a rk a d a p ta tio n . in h ib it o r u se d to tre at c h ild re n w ith in fa n tile spasm s a n d
Tw o p a tie n ts h e ld abnorm al LR G s and dark a d a p ta tio n , a d u lls w ith p a rtia l s e izu re s . Ih e d n ig is n o t a p p r o v e d b y
w h i c h r e c o v e re d s l o w l y o v e r 2 5 m o n t h s in o n e p a t ie n t a n d th e U S Food and D ru g A d m in is tra tio n b u t is u s e d e x t e n ­
& -I2 m o n t h s in t h e o t h e r . s ive ly in Eu ro p e and C a n a d a fo r tre a tin g in fa n tile sp a s m s
and p a rtia l e p ile p s y . It is th e drug o f c h o ic e in Lre a tin g

C J D O F O V I R ___________________________ i n f a n t i le s p a s m s in t u b e r o u s s c le ro s is . T h e o c u l a r t o x i c i t y
in th e fo rm o f p e rip h e ra l vis u a E fie ld c h a n g e s 2'^ ’ r e s u E t -
C id o fo v ir is an a n ti-c y to m e g a lo viru s (C M V ) a n u c le o tid e in g fr o m re tin a l n e r v e fib e r to x ic ity w ith c o n s e c u tiv e o p tic
a n a lo g and shows b ro a d -s p e c tru m a ctio n t y a g a in s t CM V, a t r o p h y w a s first n o t e d in A b o u t 4 0 -5 0 % of
w tric e lla -zo s le r v im s , hopes sum p i n t v i r u s typ es 1 And 2, a d u lts a n d c h ild re n on th e m e d ic a tio n s h o w e vid e n c e o f
a n d L p s t e i n - И а г г v i r u s . A f t e r u p t a k e i n t o c e l l s it is c o n v e n e d t o x ic ity . T h e d r u g crosses t h e b l o o d - r e t i n a l b a r r ie r a n d is
i n t o a n a c tiv e , l o n g - a c t i n g m e t a b o l i t e a n a n a l o g t o c y t o s i n e . fo u n d to be I B .5 lim e s m o r e c o n c e n tra te d in th e re tin a ,
It b l o c k s v i r a l D M A p o l y m e r a s e re la tiv e ly s e le c tive ly . U v e i t i s lh e 3 0 -] i z p h o lo p ic flic k e r is th e e a rlie s t a fT e c te d LH C
a n d h y p o l o n y are c o m m o n ( 2 5 - 5 0 % ) a fte r b o t h i n t r a v e n o u s p a ra m e te r. Ih e d ru g is s p e c i f i c a l l y t a k e n u p b y a m a c rin e .
and in tra vitre a l c id o fo v ir. D ire c t c y to to x ic ity lo c ilia ry e p i- h o rizo n ta l, b ip o la r, and M i i H e r c e lls o f t h e r e t in a w here
L h e E i u m is c o n s i d e r e d t o b e l h e c a u s e o f d e c r e a s e d a q u e o u s it e x e r t s ils to xic ity . M o n ito rin g w ilh s e ria l v i s u a l fie ld s
p ro d u c tio n . A b re a k in th e b l o o d -re tin a l a n d b l o o d - o c u l a r a n d o p tic a l c o h e re n c e m e a s u r e m e n t o f re tin a l n e rv e fib e r
b a rrie r, e s p e c ia lly in e ye s w i t h c h r o n ic s m o l d e r i n g C M V ret­ t h i c k n e s s a r e r e c o m m e n d e d . ' '■
i n i t i s . is l i k e l y r e s p o n s i b l e f o r t h e i r i t i s a n d a n t e r i o r u v e i t i s .
R e d u c in g lh e d o s e o f c id o f o v i r in th es e eyes w i t h h ig h e r b i o ­
a v a ila b ility c a n d e cre a se th e in te n s ity o f th e in H a m m a t io n . IN D O M E T H A C IN R E T IN O P A T H Y
Jh e u ve ilis responds lo c yc lo p le g ic s and to p ic a E s te ro id s .
I'h e r e are a fe w re p o rts o f re tin a l changes a ttrib u te d lo
C y s t o i d m a c u l a r e d e m a is s e e n d u r i n g i m m u n e r e c o v e r } •} 2
in d o m e th a c in ( i n d o c i n ) ; h o w e v e r, n o n e pre se n ts c o n v in c ­
in g e v id e n c e o f a causal re la tio n s h ip b e tw e e n in d o m e th a ­
R IF A B U T IN ____________________________ c i n t h e r a p y a n d t h e f u n d u s c h a n g e s . ” '''11'

R ifa b u tin is u s e d in L h e t r e a t m e n t o r p r o p h y l a x i s o f sys-

L e m i c A t y c c b o c i m u m a in 'u m c o m p l e x i n f e c t i o n s i n p a t i e n t s D IG IT A L IS A N D D I G O X I N R ET IN A L
w ilh A ID S , and s o m e tim e s in im m u n o c o m p e te n t peo-
p i e . - 27-1 H y p o p y o n u ve itis c a n b e g in w ilh in a fe w d a ys to
T O X IC IT Y ______________________________
a fe w weeks o f b e g in n in g tre a tm e n t in b o th im m u n o ­ D ig ita lis and d ig o xin m ay cause d e fe c tive c o lo r v is io n
su ppressed and im m u n o c o m p e te n t i n d i v i d u a l s . - " 1- ' ' A x a n th o p s ia , a n d o t h e r a b e r r a tio n s o f c o l o r v i s i o n , as w eEl
P a n u v e itis w it h r e t i n a l v a s c u l i t i s is s e e n r a r e l y i n p a t i e n t s as a b n o r m a l d a r k a d a p t a t i o n a n d r e d u c e d p h o t o p i c D i c k e r
w ilh p u lm o n a ry t u b e r c u lo s is .-' ' B ila te ra l co rn eal endo­ liR G a m p l i t u d e s * 3 0 1-™ lh e fu n d u s appearance is u n a f­
th e lia l d e p o s it s , in t h e a b s e n c e o f i n f l a m m a t i o n , h a v e a ls o fe c te d . Ih e p a tie n L m a y o r m a y n o t c o m p la in o f dyschro-
b e e n re p o rte d w ilh rifa b u tin use in hum an im m u n o d e fi­ m a to p s ia . C o lo r vis io n t e s t i n g is a u s e f u l m e a s u r e in th e
c ie n c y viru s ( J 11V ) -p o s itiv e a d u lls a n d c h i I d r e n . J ''i t U M T h e d ia g n o s is o f to x ic ity o f th es e d ru g s a n d m a y reveal b o th
s te lla te , r e fr a c tile e n d o t h e l i a l , d e p o s it s a re firs t o b s e r v e d in re d -g re e n and b lu e -y e llo w d e fic ie n c ie s , L o n g - t e r m use o f
tbe p e rip h e ry , and m a y e v e n tu a lly e xte n d lo in v o lv e th e d ig ita lis even al th e ra p e u tic d o s e s causes re d -g re e n and
c e n tra l corn ea. These d e p o s its are a s s o c ia te d w ith fla re i r i L a n d e f i c i e n c y i n 2 0 - 5 0 % o f p a t i e n t s . ' 1' ’
a n d c a n o c c u r in e ye s w i t h o u t a s s o c ia te d in fe c tio n s su ch
as C M V re tin itis . O v e r tim e , th e d e p o s its m a y take o n a
g o ld e n hue and progress d e s p ile c e s s a tio n o f rifa b u tin .
G L Y C IN E R E T IN A L T O X IC IT Y
A n te rio r le n s d e p o s itio n , v itre o u s o p a c itie s .^ 6 c y s to id A S S O C IA T E D W IT H
m a c u la r e d e m a , and a re ve rs ib le re tin a l d y s fu n c tio n
T R A N S U R E T H R A L R E S E C T IO N
h a v e b e e n d o c u m e n t e d in e x p e r im e n t a l s tu d ie s .-^ 1
The m e c h a n is m fo r u ve itis is n o t c l e a r l y u n d e rs to o d : G ly c in e is t h e m o s t c o m m o n l y u s e d irrig a tin g s u b s ta n c e
p o s s ib ilitie s in c lu d e d e p o s itio n of im m u n o g lo b u lin s or d u rin g tra n s u re th ra l re se c tio n and e n d o m e tria l a b la ­
a n tirifa b u tin a n tib o d ie s , a lth o u g h rifa b u tin in v iv o does tio n s . E x p o s u r e o f t h e p r o s ta te v e n o u s s in u s e s m a y a llo w
not a lte r c e lE-n ie d ia le d im m u n ity . The in fla m m a to ry ' e xce ssive a b s o rp tio n o f g ly c in e , w h ic h , when reaches
re s p o n s e can he e xa c e rb a te d by c o n c o m ita n t use o f rnacro- le ve ls o f a p p ro x im a te ly 4 0 0 0 jim o l/] ( > j 5 0 n i^ 'd l) , m ay
Eid e s '1 o r a z o l e d r u g s s u c h as f l u c o n a z o l e . T h e u v e itis cause tra n s ie n t v is u a l d is tu rb a n c e s such as "d a rk e n in g "
r e s p o n d s to d i s c o n t i n u a t i o n o f r i f a b u t i n a n d i n s t it u t i o n o f o f v i s i o n , o r s e v e r e v i s u a l Loss f o r u p lo several h o u rs . ’a '
t o p i c a l s t e r o i d s a n d c y c l o p le g ic s . G ly c in e a b s o rp tio n re s u lts in excess flu id a b s o r p t i o n and
d ilu tio n a l h y p o n a tre m ia , re s u ltin g in р и Щ ооаф edem a tra n s itio n a l, and p a n c re a tic cancers. A 5 У -y e a r-o ld m a le
and e n c e p h a l o p a t h y . ш > ' ' JJ Fu n d o s c o p ic e x a m in a tio n t r e a t e d f o r n o n s m a l l ce ll l u n g c a n c e r d e v e l o p e d P u r t s c h e r -
is n o rm a l. V is u a l lo ss is a s s o c ia te d w ilh ER G changes lik e re tin o p a th y and p e rip h e ra l v a s c u la r o c c lu s io n s
c o n s is tin g o f lo ss o f o s c illa to ry p o te n tia ls and a lie n n a ­ in vo lv in g th e d ig its a n d dorsal p e n is a lo n g w i t h p o s itive
tio n of" 3 0 - 1 \ z "flic k e r fo llo w in g ." rl h i s re tin a l d y s fu n c ­ a n l i n u c l e a r a n Li b o d i e s a n d a n e l e v a t e d s e d i m e n t a t i o n r a t e .
tio n m ay be th e r e s u l t o f g l y c i n e ' s r o l e ль a n in h ib ito ry D is c o n tin u a tio n o f th e drug and s y s t e m ic ste ro id s q u i­
n e u ro lra n s m itte r. e te n e d th e le s io n s , t h o u g h th e y p e rsis te d f o r t i - 1 0 m o n th s
w i l h l o s s o f t h e f o u r t h d i g i t . *■'

F L U D A R A B IN E T O X IC IT Y
l l u d a r a b i n e is a p u r i n e a n a l o g a n t i n e o p l a s t i c a g e n t w h i c h ACUTE M ACULAR
has been trie d in p a tie n ts w it h a va rie ty o f l y m p h o p r o lif - N E U R O R E T IN O P A T H Y
e r a t i v e m a l i g n a n c i e s a n d as a n i m m u n e s u p p r e s s o r b e f o r e
s t e m c e l l t r a n s p l a n t . O c u l a r t o x i c i t y is n o t c o m m o n a t t h e
A FTER IN JE C T IO N O F
l o w - d o s e r e g im e n . H o w e v e r a p h a s e [ s tu d y s h o w e d lo ss o f S Y M F A T H O M I M E T IC S_______________
v i s i o n i n л \I b u t t w o o f t h e 13 p a tie n ts w h o re c e ive d h ig h -
See C h a p te r 11.
d o s e flu d b irlb io e l h e v i s u a l [ о н is i r r e v e r s i b l e a n d p r o g r e s ­
s ive , e x c e p t in ra re in s ta n c e s w h e r e v i s i o n im p r o v e s . L o s s o f
b i p o l a r c e l l f u n c t i o n o n E f t G is f i r s t n o t e d , h i s t o l o g y s h o w s D R U G - IN D U C E D A C U T E M Y O P I A
d r a m a t i c lo s s o f g a n g l i o n a n d b i p o l a r ce lls, lo s s o f m y e l i n ,
C h lo rth a lid o n e , h y d ro c h lo ro th ia zid e , tria m te rin e , and
a n d s e v e r e n e c r o s i s o f l h e o p t i c n e r v e . 11' I n a d d i t i o n , r e a c ­
t o p i r a m a te a r e k n o w n lo in d u c e acu te m y o p ia w ilh re ti­
tiv a tio n o f a c u le re tin a l n e c ro s is a n d o th e r o p p o rtu n is tic
nal fo ld s . A v a ria b le d e g re e o f c ilia ry b o d y s w e llin g , c ilia ry
v i r a l a n d f u n g a l i n f e c l i o n s a r e s e e n . ]3Q
m u s c l e s p a s m , p e r i p h e r a l c h o r o i d a l e ffu s io n s ., a n d f o r w a r d
m o v e m e n t o f th e iris le n s d i a p h r a g m c o n trib u te to w a rd s
G E M C IT A B IN E PU R T SC H ER - LIK E th e п п )ю р ic c h a n g e . M o s t o f th e s e a re t r a n s i e n t a n d co r­

R E T IN O P A T H Y re c ta b le o n d is c o n t in u a t io n o f th e d r u g . P a tie n ts o n
t o p i r a in a te o f t e n develop b ila te ra l o r u n ila te ra l a c u le a n g le
G e m c iM b in e is л n u c l e o s i d e a n a l o g u s e d Lo tre a t o s t e o ­ c lo s u re g la u c o m a re q u irin g m e d ic a tio n s , and s o m e tim e s
sarcom a, n o n s m a ll c e ll .lu n g cancer, b re a st, o v a ria n , p e ri p h e ra l i r id e c lo m y o r i r id o p la s ty .'1 1H "
 42. Pv,idcr1 Ti. Tncn-Ji2irtE\>tv STiTf ie; рэмЙн- ^ch ЗрПЙ'этз! '973.9i3:25H3
References 43. ds Manoeie J. Ct:js № ices probced b; с р'тзгаишге а л Ihс icftzi ?.. .i xa Can
Ee nittr HZrafie N,FW*iH fliTlw'HiirdaxEfiMcf cHaoiira.&iffist Oii li’an -J OpKtanclScc 19S2:2E:'60-7E.
IS£^?35--S2 44. Fл г и Sa TnisrtSiz ne ffJoclmie iMBilsnt-Ы : рсп^иаг^ diэтс-neli t^Ty. n: 5mft
Et.n-JeyJr Д iXJasEL.Ftyx.SJ.L&'Kilsiir илме! difcrcqiite mtnqHttyatotittftH JL solot ^т>'Зр||!тг1та'Х1,т й 1M2. fJEirM Йазят; 1331. з 09-19.
егi fd csjfli ton J CfhnalrocJ 197&;S& - 11. 43. t^gcr,' \h. -■uiTf DW.IMgxRl: DlfetHss г ihs i ^п-эт.;::: к&х cl LlitDfMunEinc
Ca(v нЕ.йа.ш F.Guritd FD. CJibroodnen3 rcratty fwtn' kfcdmb,1rai ih'sihcidlsl. plmrtiarittinralwEb JFtS^ I9r0102:12HO
№ tolhantfi £6.75:171-6. ^й. кхй J Ex^thDTfH hm ^ Fjelia mup/ owe cp ng j c c tfucflline tren^. t o P?:^r
tan ^E.Hert:nd ^ eclCtJa d aTmaauMtJce; mc-ls-ir Falm-up. T 1®tf&442-7.
Ш О рИ ЦтйЩ Еб 736-44. A7. Kntjaqh BO.Carftiil RjHlixdaine edsm \r. humor up Am ^ikirnDf
ЕккюшШ He useofArndff g ii пЕап^сиэ'хите re:t :LD£l у. CcmhsJroDfDn' lffil 99:2160-9
Ш4:ЭТ:1ЭЙ-?2 ' ' ' 43. Кягг D Doft Й-. ирУшш J. ’■immja' thiaiilams геП-с-раГ;,'. flena 1934:4:263-6.
Fracas J. ce ^jckA Camte E.eI а. ЯЁ&нинЙш(йанайсш. SJlldmotoa h3. Heuifti A iViti'a FM.'n \erscr h '} Frcirgiii^ (htftafetinop^ cits1 receis ng IhcriJazne.
19$Ш 81-9& ^irOxiran c igAlSfil'tlM
fiMcobflyd Lie er^e 4lh Bd.E|Hi[#ied, LCCTTh t e . '993. p. 371-62 33. Milef ll FI Ёjt-M(amЖ tira IE. Clntsl-JIikutjelu'a вяьЛ1cl Ih reli cpiJ^1.
Hart J1WM 3j'3i RU JDtinsimSP £ £j. S'Jb: p#н" й1г^inditotuu he 'El rHpfltry; parted OpTT^ lSffi-0D 14:8-66
piltcirs d hiiid 1ей яергезеп An CfhnoncJ 1964.' 377-60 51. Fctl: № . iMai pйпй1 aodpt’siclhiuifl змпрйпа;. 7гапз fti OctiCHbiDl 5oc
3 тк п Ы ц JR, №li C. _ew^Йкшкще гетс^ог^. AmJ Oxiiiairo. '930:99:1 EC. 1562 60:317-E2
10 IfefiHnl P Ccrr ^E.Sh^i I f,-1. Eaih сИлшге relrcpzJIv dnMandftnclnnal tiidiiqbArcll 32. Fell: AM. 'His rsacl m й pcms t n v Hlh xtAtiE е р н ш ё CptiEHlmoi
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293 lemnifj J:. О Ва ле IJ . Nr JT. [a-frDr rnnwide reUicfaty. AmJ O^d airc
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291 гегсик-| ii: EiiiKs frU. ChaarohoGE^. Саичп ъж и de 'el nspalb^ ton ifilhama
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293 '.sHeyJi. &jfhacleus Gj. FhI ra: he™haige г sJiaajte ■дПмт гаж л ъ pcianirg.
spc sines ii тстк -й^ fcfct^d i f же fljes. J^Ji^. 1978 233:1 El E-7
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This page intentionally left blank
Infectious Diseases of the Retina and Choroid
In fe c tio u s ag en ts m ay be c a rrie d fro m e ls e w h e re in th e [ rt.O: Bacterial septic embolization ot the relina and
b o d y a n d cause o n e o r m o r e fo c i o f in fe c tio n in th e re lin a optic nerve head.
a n d l e s s o f t e n En t h e c h o r o i d i n o n e o r b o t h e y e s , [ f H e a l e d
A Lo F: This 12-yea r-okf j^irl noLed blurred vision during an
e a rly w ilh s p e c ific a n tib io tic s , th e o c u la r dam age m ay acute iefafile illness-. Visual acuity was 15/400. There was mas-
be m in im ize d ( l:ig u re 1 0 .0 ] I in fe c tio u s d ise a se s can be inlianeCinaI Lind subnet inn I exudation in- lhe macuJai and
c a u s e d b y b a c te ria , fu n g i, v iru s e s , a n d p a ra site s . T h e y c a n juxlapapilbry reruns (Al. There were peripheral pale bos
in v o lv e b o th th e re tin a and th e c h o r o id . C e rta in a g e n ts of rhinitis surrounded by multiply Rolh^ sfKifls (Б япс1 Q .
Angiijgraplw revebled leakage qf dye from lhe leKion ,il lhe tem­
c jn c o n tig u o u s ly spread to- th e vitre o u s c a vity c a u s in g
poral margin ol Lhe optic disc {□). Coagulase-posiLive staphylo­
e n d o p h th a lm itis , w h ile c e rta in o th e rs are lim ite d lo th e
cocci were cultured from (he blood and a denial rout abscess.
re tin a a n d c h o r o id , fn s o m e in s ta n c e s w h e n b a c te ria a n d
re c ^ ty & d in H a v e n o u s a n t ib io t ic Ih u r a p v . О п у year la lo r i t
fu n g i g a in e n tr a n c e in to th e v itr e o u s , e ith e r e n d o g e n o u s ly and F l, v is u a l a c u it y had im p r o v e d to 2 0 / 2 5 . A rrow in d ic a t e s
o r e x o g e n o u s ly , v H ritis w i lh o r w it h o u t p e rip h le b itis m a y n v i LrtHJUK v e i l o n th e o p tic n e r v e h e a d s e c u i K i a r y to p o s l e n o r

b e th e e a rlie s t s ig n o f a n e n d o p h t h a l m i t i s ,1 s e p a r a t i o n u l" I h e v i l r e o u s . F o c a l c h o r i o n e l i n a l s e a he- r e m a i n e d a t

L h e s i t e o f s o m e o f l h e а т е а ? o f r e l i n i t l s ( c o m p a r e CJ a n d t- ■.

G Lo L: Metastatic baclerial rmin-itis^ m a c u l a r slar, and pap­

illitis (C a n d H ) occurring in a 32 - y e a r - o l d m a n w h o w a s
P Y O G E N IC C H O R IO R E T I N I T I S receiving zidovudine TAZTf and aciclovir fZoviraxf because
S e p tic e m b o li c o n ta in in g b a c te ria d e riv e d fro m fo c a l
of H IV poMlivjtv for 10 y e a r s . He com plained of d e c r e a s ­
ing vision in h i s right e y e of 2 monlfis'' duration. M edical
areas o f in f e c t i o n s u c h as d i s e a s e d h e a r t v a lv e s , o r fo c a l
workup, Including blood cultures, was negative. Visual acu ­
abscesses in v o lv in g th e te e lh , s k in , o r o th e r o rg a n s , m ay
ity w a i 20/400 i n the rijjhl e y e . ГЬ и е w ere minimal val rebus
L o d g e in ( h e r e tin a a n d p r o d u c e fo c a l w h i t e areas o f re ti­ ce3ls. Si к weeks after 1г е и I m e n l w i L h doxycycline Ihe lesions
n i t i s a n d o v e r l y i n g v i i r i t i s (I i g u r e s E 0 .0 1 and J0 .0 2 ) . T h e s e showed evidence o f early resolution. Note the angiomatous
m ay be a c c o m p a n ie d by w h ile -c e n te re d h e m orrh ag es appearance of the oplic disc lotion >1 and Ю. Three rnonths
( E 'ig u r e s 1 0 .0 I , B; 1 0 .0 2 . Ii). I jess fre q u e n tly th e se p tic lalej L h e lesions h a d resolved <L). His visual acuily, h o w e v e r ,

e m b o li lo d g e in th e c h o r o id and m a y p ro d u c e a s u b re ti­
had improved o n ly s lig h t ly to 2U/tfO.

nal abscess (see ]: i g u r e 1 0 .0 3 , Л -C J ]. M o a t p a tie n ts w it h

b a c te ria l re tin itis w ill have s ig n s and sy m p to m s o f sys­
suspicion is necessary to delecL those who are ambulatory
te m ic illn e s s , i n c l u d i n g fe ve r, c h ills , e le v a te d w h i t e b l o o d
with evidence o f disseminated sepsis in iheir eyes.11
c e ll c o u n ts, p e le c h ia e , s p lin te r hem orrhages o f th e n a il
bed. and p h y s ic a l fin d in g s p o in tin g lo th e p r i m a r y s ite
o f th e in fe c tio n . R o th d e s c rib e d w h ite re tin a l le s io n s a n d F O C A L IN D O L E N T M ET A ST A T IC
s e p a ra te hem orrhages in p a tie n ts w ith s e p s is .1 : Litte n
d e s c rib e d w h ite -c e n te re d h e m orrh ag es in p a tie n ls w ith
B A C T E R IA L R E T IN IT IS IN
e n d o c a rd itis and c a lle d th e m 'R o th 's s p o t s ' . L' ' [ ' h e w h ile A C Q U I R E D I M M U N E D E F IC IE N C Y
c e n te r [n a y c o n ta in o rg a n is m s , a lth o u g h m o s l a re s te rile S Y N D R O M E (A ID S )
a n d a re c o m p o s e d o f w h i t e b l o o d ce lls, f n m a n y in s t a n c e s
t h e w h i l e c e n t e r is c o m p o s e d o f f i b r i n o c c u r r i n g a l t h e s i t e P a tie n ts w i l h A I D S m a y d e v e lo p m u l t i f o c a l , d isc re te , y e l­
o f e x tr a v a s a tio n o f b l o o d f r o m th e re tin a l b l o o d v e s s e ls / ­ l o w - w h i l e p a t c h e s o f b a c t e r i a l ret i n i its t h a t e n l a r g e s l o w l y
R o t h 's s p o ts o c c u r m o s t f r e q u e n t l y i n p a tie n ts w i t h severe over w eeks, and a c c u m u la te la rg e a m o u n ts of s u b re ti­
a n e m ia fro m a n y cause, in c lu d in g le u k e m ia a n d s u b a c u le nal flu id a n d fib rin o u s e xu d a te w ilh m in im a l in fla m m a ­
b a c te ria l e n d o c a rd itis . If b a c te ria l se p sis is su sp e c te d - t o r y cell r e a c t i o n i n th e o v e rly in g vilre o u s (fig u r e 1 0 .0 1 .
prom p t m e d ic a l e v a lu a tio n , in c lu d in g b lo o d c u ltu re s , a G - l . J . 1- '['h is f o r m o f i n d o l e n t b a c t e r i a l r e t i n i t i s is c a u s e d
s e a rch f o r th e p r i m a r y s ite o f th e in fe c tio n , a n d in s titu tio n b y re la tive ly n o n p a th o g e n ic b a c te ria , s u c h a s Rh&nacoccus
o f a n t i b i o t i c t h e r a p y , m a y s u c c e e d in p r e s e r v a t io n o f u s e ­ ctjui a n d (s e e d is c u s s io n o f c a t-s c ra tc h d ise a se in
fu l v i s i o n in s o m e p a tie n ts (K ig u r e Ю .0 1 ) . O v e rt e n d o p h ­ t h e n e x t s e c t io n ), l h a l u s u a lly r e s p o n d l o o ra l d o s y c y c lin e .
th a lm itis m ay re q u ire pars p la n a vitre c to m y in a d d itio n In im m u n osuppressed p a tie n ts th e re tin a l le sio n s m ay
to in tr a v e n o u s t h e r a p y i f p ro g re s s io n o c c u rs . 'Ilte m a j o r it y be m is ta k e n fo r th e m o r e fre q u e n tly e n c o u n te re d re tin a l
o f p a lie n ls w ith m e ta s ta tic b a c te ria l re tin itis are a lr e a d y i n f e c t i o n s c a u s e d b y H e r p e s v ir u s e s , C tfn iJb Jfl, С п 'р 'К я х ч т ш .
h o s p i t a l i z e d f o r t h e i r s y s te m ic illn e s s , b u t a h i g h in d e x o f a n d ib x o p ltis rrnr o r g a n i s m s .

B A C T E R IA L C H O R O I D A L A B S C E S S
P a tie n ts w i l h fo c a l b a c te ria l in fe c tio n s m a y d e v e lo p s e p tic
e m b o l i Lh al m a y lo d g e in e ith e r th e re tin a l o r th e c h o r o i­
d a l c ir c u in it io n . In t h e la tte r ca se a c h o r o i d a l a n d s u b re ti­
n a l a b s c e s s m a y d e v e l o p £f i g u r e s L fJ.0 2 , A - С ; I'ig u r e 1 0 .0 3 ,
A - C ) .'y ii
I fl. 0 2 M e t a s ta t i c b a с te ria l re ti n itis .
A Ld D : Ttiis 32-year-old wom an presented w ilh J-w eek his­
tory oJ visual blur in Line left суп. There was а focal area of
ouler retinitis surrounded by exudates :Al. The fluorescein
angiogram showed hyperHuorescence and late staining
and leakage of Lhe lesion 'B and C). She had a small area
ul swelling of the lip of her m iddle finger on lhe left hand,
diagnosed initially ль ее 11ul i Us and 1гел led With oral anLi-
biolics. The infection did nol respond and spread quickly
and she was subsequently lound Co have meticillin-Tesislanl
i'r aphyfoi'tjcL'us n ureu* :М.КУА . She was started tin 3V vanco­
m ycin. There was no history ol" im m unocom prom ise or visits
Lo hutpilal от nursing homes. i?he responded lt> vancom ycin
and [he lesion resolved, Eeaving в flat pigmented scar ID).
F Lo H: 7h is 42-year-old man presented wilh lever, nighl
rtveats, spots on his legs [F and CL".and blurred vision for 2
weeks. Six weeks after his initial visit to lhe emergency room a
punch biopsy of lhe spot on his leg shbwed endoihelial swell­
ing ol lhe small vessels, fibrin deposits and infiltrate ot red
cells, neulrupbils and nuclear dust diajjnosed as lt*u косу toe las-
Lic vasculilis 'HL'nocb-Schonlein purpura, H5frL He was given
я methylprednisolone iM ediolj {lose back lhat he Look off and
on for 4 months. He continued Lo have fever and nigh I-^weals,
rind had a 40 lb ■ . Ltikg.i weight lo*s. H it visual acuity was
20/25 in :lit! right eye and 2(J.'4i»J in the lefl eye wilh an affer­
ent papillary defecL. The Felt fundus showed several nerve fiber
infarcts and relinal hemorrhages It). He returned lo lhe emer­
gency nutmi w hen he was found Lo have' a heart гпиттит anti
a hislory of rheumaLic fever, kchocardio^ram revealed vej^ela-
Li<jns. he wa* anemic with a hemoglobin of fr.l ^ d L f and hail
urinary red blood cells and granular casls. Lilood ( nil иге ^new
ActifrobacHlus actirtom ycelt'm iom iU m s. an organism found in
ihe ■ a I ' /л i:.\. I [e ,n- unvent replacement "■ his mitral and
aortic valve: the hemorrhages and nerve fiber infarcls cleared,
lh e mpchanrisfii of Ihe Purlscher-like retinobfttlift is likely from
the vasculitis associated With 1-liP and lhe immunoiogical
changes from sjbacu tE Ijacterial endocarditis, Kopnesentative
f^oss picture of a vo^el-ation bn lhe aortic valve (I),
j lo L: "111is 46-year-old white man presented wilh a painless
decrease in vision in both eyes for 2 monlhs. He had a bis­
tory of diabetes,i cocaine use, and chronic dt?up vein ihrombo-
sis, and was hospitaEizjed 2 Weeks prior (o Loss of vision w ilh
fevers, elevated vthite cell cuunl, and diabetic ketoacidosis.
H it blood cultures ^row S t jp h . aureus, which was resistant
iii ■:;-n t illin. l-le bad had ,i 1.1 cm prcsl.” < .ii>-■ . ( -ss u+iich
required surgical drainage. He was treated with nafcillin and
rifampin (rifampicin). The patient slopped his antibiotics and
the fevers and liaclerem ia recurred which was felt Lo he from
an infecLed ibrtwnbus in Lhe leg. The thromfru-s was excised
and be was restarted on anLibiotics. His visual acuity was
counting fingers at b feet in the right eye and counting fingers
al 4 tc43t in Ibn left eye. There were 2+ anterior vitreous cells,
vitreous hemorrhage in Lhe right eyer prerelinal gliosis, and
an area of t horkjret inovi Lrea I neovascularization (J). In Lhe Sell
macula, he had an area of choriorelinoviLreaI n ew vessels iK:.
lh e fluorescein angiogram of Che lefL eye shows a lacy pa Hern
Lo lbe vessels Lbal w ere present on the surface o f Che relina (Lf.
This palient developed a chonorelinoviLneal neovascularizalion
in areas ol atrophic scars caused by blaph . aureus netinilis. The
neovascularizaLion conlinLicd Lo giow and shtjwed e\'i[lence
ot hleutlinj;. Q plical coherence LomograpK' iO C I ■ shov^ed
tbe presence of vessels on the surface of the retina with con­
traction of lhe poslurior hvaloid and shadowing effect from the
blood. He Lindurwenl panretina I photot-Toagulalion wilh partial
into kit ion of Ihe chorioi-et inovi trea I neovascularization.
iGuurtesy: A-D, Dr k/jliurl Millr.i: t-l I. Dt Млгк U,ulv I Ur. lu-^.Ur
L!m vt.t H o l d l .1i i U D r J.liim 's h i l k ■
N O C A R D IA ! fl.0 3 B a c te ria l s u b m a c u la r a b s c e s s e s .

A lo C: Subm acuLir baclerial lAi Ln л i^-year-old

М щ й и d u ie r a irfe i is л g r a m - p o s i t i v e f i l a m e n t o u s b a c t e r i u m Woman hospitalised with dis-sc^-mirnjiLod lupus erythematosus,
found in so il and d e c a y in g ve g e ta b le m a tle r th a l s h ire s s o m e gram-positivn1 EjacLerial e ndocafd il is, septicemia, jififlieehia^.
fe a tu re s w i t h f u n g j . El is an o p p o r t u n i s t i c p a l b o g e n k n o w n and a 1-day history o f loss of cenlral vision in Lhe lell -eye.
Lo a J e c t t h e r e l J n a a n d c h o r o i d i n a s m a ll n u m b e r o f so lid Fluorescein angioyraphy revealed evidence ol" a nonvascu-
orgin Lraosplant i f i ^ p l e n t i l > - l t i \ . jasfenrides a cco un ts fo r lari;codr nonfluorescenl submaculair exudate and I ale leakage
□E dye from the overlying retinal vessels (B and Cl. Several
S O -W ^ -o o f h u m a n in fe c tio n s , f o l l o w e d b y N . fo m ifie ru ti, N .
days later she developed massive purulent endophLlialmiris.
ftiim iic H ' a n d N . n e w i J h e i n f e c t i o n is g e n e r a l l y d i s s e m m a t e d
w i t h abscesses i n v o l v i n g (he lu n g , b ra in , s k in , eye, a n d o th e r Notardia Retinitis.
sites. I l b e g i n s a s a s o l i t a r y s u b r e t i n a l or c h o ro id a l y e llo w D to H : N o ca rd ia sub-retinal pigment epil helium (KFEJ
Le sio n th a l grows in s iz e w i l h n e u 1 sa tellite L e s io n s a p p e a r i n g abscess ID ' in a 70-year-old man w ilh Hodgkin's disease.
Angiogfaphy shew ed a nonvasculari^ed subrelinal mass
p y e t d a ys (I'ig u r e 1 0 .0 3 D and Е]. O v e r l y i n g r e l i n a l h e m o r ­
with LaLe leakage of dye from reliral vessels into the v ilrt'CJLis
r h a g e s a r e s e e n ( F i g u r e 10.03r D - H ). D i a g n o s i s is b a s e d
iii anti Г>. There was a suEi-Rl^L abscess lying helween Lhe
o n d e m o n s tr a tin g lh e o rg a n is m by a tra n s v itre a l fin e n e e d le necfolic relina and lhe choroid (C i. l-ilamenlous branching
re lina l b io p s y , blood cu ltu re s, o r b io p s y o f a n y o l h e r affecLt’d orgisnisms (^rroivi) were present in lhe t. hrjri uci] pi Maris and
s i L e . 1" J lin g le sio n s are q u i l e c h a ra c te ris tic o f N o c a rid a o n along EJruch's membrane I arrows, Hi.
M W ( F i g u r e 1 0 . 0 3 J ). J h e o r g a n i s m is a g r a m - p o & i l i v e b r a n c h ­ I Lo K: This 35 year old east Indian m ale w ith a 2 year history
i n g h y p h a . T r e a t m e n t c o n s i s t s o f r e d u c t i o n o r d i s c o n hnua- ot nephcolic syndfomc secondary Lo M PCiN was on 10 mg
ef pTednisono daily. He presented w ilh bilateral si m u l i g n e ­
Lion o f im m u n o s u p p re s s iv e s and in s tilu Lio n o f a p p ro p ria te
o u s acute v i s u a l E o s s Co light perception i n e a c h eye associ­
a n t i b i o t i c s / a s u c h as t r i m e t h o p r i m - s u l f a m e t h o x a z o l e , - a m o x i -
ated w i t h periocular pain, redness and chemosis. Both fundi
ciil i n - c l a v u l a n a t e . i m i p e n e m - c i l a s l a l i n , c e f o t a x i m e , d a r i l h r o -
showed m ullipie subretinal y d low infill rales w ilh exudative
nwdn, a n d c i p r o f l o x a c i n . J,‘i relinal del<bchmenL and scattered relinal H e m o r r h a g e s i l l . He
developed hypotonia and seizures w ilh in 7 days. H e was
treated variously tor tuberculosis, loxoptasmosis and fungal
infed ions with no impruvemenl. His neUfological and dcii-
E a r conditions worsened. Vi I rectomy, orfailal biopsy and serial
CSF examinations did not yield a causative organism. MKI
showed ring lesions (Jl initially and a right parieto o ccip i­
tal mass (Kj laLer. Eventually, biopsy of l h e parietal mass
revealed nocardja. The patient w j i then IreaLed with imipe-
nem; his infection cleared up buL he was b l i n d in both e y e s .

11
M J a n d t i f r u i T t L k s r t f c f C j S t 'l . . . . " | i ' j >l ■Г -i d w i l h p e r m i i i i i n I ru m
4
| к - Л т а ч С а л | u u m . n l o l U p h L h j lm L * l u |j ;y .: c u | j y n | q h l by i h t U p h lh n lm ic
P u b lis h in g C l k : I Lu K . D r . I £ r : n . 4ii [r e h jn .
CAT-SCRATCH D IS E A S E : ;- ; B e n ig n m u lt if o c a l re tin itis a n d p a p illitis c a u s e d
b y c a t-s c r a tc h b a c illu s a n d o t h e r b a c te r ia o r v ir u s e s o f

C a t - s c r a t c h d i s e a s e ( C S D ) c l a s s i c a l l y is d e s c r i b e d as t e n d e r lo w p a th o g e n ic ity ^

re g io n a l ly m p h a d e n o p a t h y d e v e lo p in g in a s s o c ia tio n W ith Л to D: This 32-yeaT-old wom an noled floAtera and а рагл-

a p r i m a r y s k in Le s io n re c e iv e d as a re su lt o f c o n ta c t w i t h cenlraE scoLoma in Ihe right eye soon alter Iw u episodes of
e ats, te n n e d P a r in a u d 's o c u lo g la n d u la r fe ve r. Ib is m ay □hilts and fever. Her visual acuity was 20/20 in the right eye
he a c c o m p a n ie d b y g e n e ra lis e d ache, m a la is e , a n o re x ia , cinr I 20/2 5 in Ihe1-left eye. In Both eyes she had m ultiply focal
and o c c a s io n a lly fe ve r. W hereas a scra tch is th e com ­
areas of inner retinal Whitening. O ne of these A) was
associated with otjsLrudion d f ап inferior Is n m j^ l Enanch
m on m o d e o f tra n s m is s io n o f C SL> , il m a y be tra n s m it­
relinal artery. A focal lesion was present nasally an the lefl
te d b y c a t b ite s , lic k in g , o r h a n d l i n g o f o b je c ts a s s o c ia te d
oplic disc ijrroiv. til. AH of Lhe lesions stained (arrows, С and
w ith cats, p a rtic u la rly k itte n s . C S D is c a u s e d by a p le o - □ M edical evaluation was unremarkable excepL lor some
t n o r p h i c g r a m -n e g a t iv e b a c illu s * re fe rre d to p r e v i o u s l y as elevalion af cardiolipin antibody. O n e year later she was
th e h n g lis h - W e a r b a c illu s , d ie ftm rfa rffm u fti b a c i l l u s , and hvell and had 20/20 visual acu ily bilalerallv.
r e c e n t l v Ь 'О П Ш е Н а ^ u I t is a w o r l d w i d e z o o n o t i c d i s e a s e : t : This 21-year-old wom an in Lhe second IrimcsLer c f preg­
[ b e c a t f l e a C te n o c e p h tilid e s fe tis is t h e t r a n s m i s s i o n v e c t o r nancy noted floalers and visual loss in Ihe left eye 2 weeks
following an episode of fever of unknown origin. She owned
b e t w e e n ca ts. T w e n t y - o n e s p e c ie s o f Bartxmelia have been
seven cats EjuI could recall no hislorv of be ini’ scratched.
id e n tifie d e ith e r b y c u ltu re o r p o ly m e ra s e c h a in re a c tio n
Visual acuily in (he left eye w as counting fingers only. O n e
( P C R ) , e ig h t o f w h ic h are k n o w n t o c a u s e h u m a n d is e a s e Lo 2 - vilreous cells were prosenl in Ihe lefl еущ. .Vlullitocal
in c lu d in g CSD , tFe n c h fe ve r, e n d o c a rd itis , m y o c a rd itis - white lesions interpreted a s inner nelinilis were presenl
O roya fe ve r (C a r r io n 's d is e a s e ), and re tin itis , th irta n e lh i in both eyes (a rro w s I. O n e o f these was associated w ilh
heusehie, Б . Q u in t a n a , if. e & a b e t h i l e H a n d B . g n th n m ii c a u s e obsLruclion o f Lhe superotempofal branch retinal artery in the
o c u l a r le s io n s ." ' l h e fo c a l w h i l e r e l i n a l l e s i o n s m a y o c c u r
lelL eye. M edical evaluation, including blood cuElures, was
negative.
anyw here in th e fu n d u s hut have som e p re d ile c tio n lo
F lo H: This 28-year-old man w ilh A IL Ji noted Etlurred Vision
o c c u r a d ja c e n t to a n d o b s tru c t m a j o r r e tin a l a rte rie s a n d ,
in the [eft eye associated w ith mullipfe foci of relEnitis and
Eess o f t e n , v e i n s [ f i g u r e 1 0 . 0 4 r A - i ! ) . papi.iiMs lamaWS, F-H). O n e lesion utrirftf s tra w , Fl caused
T h e s e re tin a l le s io n s , as w e ll as s im ila r le s io n s i n v o l v i n g obsLruclion of Lhe inferior branch retinal artery.
th e o p tic n e rv e h e a d , m a y b e a s s o c ia te d w i l h an a n g i o m a ­ [ lo L: This Eiealchy 22-year-oEd man had a 2 -week history
t o u s p r o l i f e r a t i o n o i 'c a p i l l a r i e s (E: ig u r e s 0 .0 4 , E - E . ) . ' 1 ° T h e of blurred vision in lhe righi eye. H e owned manv liouse-
w h ite le s io n s ty p ic a lly i n v o l v e th e i n n e r h a l f o f l h e re tin a
hold calsr was frequently scratched, but denied recent Ill­
ness. Visual iscuily was 20/200 in Lhe right eye and 20/20
a n d m a y o r m .a y n o t b e a s s o c ia te d w i t h o v e r l y i n g v itr e o u s
in tEie l e f t eye. NoLe the h f f lf i i г п а с u I a r stA r, exudative reLi-
ce lls. T h e y m a y s im u la te c o t to n -w o o l is c h e m ic spoLs, buL
naL deta ch m cmI, and focal retinilis -tirmw, L'i enveloping EjuI
Lb e ir d i s t r i b u t io n in t h e f u n d u s is n o t n e c e s s a r i l y a s s o c i ­ nui obstructing lhe inferior branch relinal лг1ету. Л simi­
a t e d w i t h t h e d i s t r i b u t i o n o f a f i r s t - o r d e r a r t e r i o l e as is t h e lar bul smaller local area of leLinilis was presen I in the lefl
case xvilh c o l t o n - w o o E s p o ts . eye \л т ш щ , J). NoLe 1Ье? pseudoangjomalous appearance of
ЗЪ е fo c a E w h i l e r e t i n a l a n d o p t i c d is c l e s io n s , s w e l l i n g Lhe acLive lesion angiographicAlly {arrow , K). BoLh lesions
o f th e o p tic d is c , a n d m a c u la r sta r fig u re ty p ic a lly c le a r
stained LtK W ith in several weeks Ete recovered normal vision
wiLhoul L r e a t m o n l .
s p o n ta n e o u s ly w ith in several weeks or m o n th s and th e
v is u a l a c u ily u s u a lEy re tu rn s lo norm al or near n o rm a l.
M o s t o f th e re lin a E le s io n s re s o lve w i t h o u t c a u s in g re tin a l
p ig m e n t e p ith e liu m (R P EJ d a m a g e . :jtl In 1У77 and 'L b e C S I> b a c illu s m ay a ls o cause a c u te e n c e p h a lo p a ­

1 9 Й 7 th e a u t h o r n o te d th e a s s o c ia tio n o f CSED in p a tie n ts th y and o th e r n e u ro lo g ic and s y s te m ic m a n if e s t a t io n s in

w ith E -c b e r's s l e l l a t e n e u ro re lin itis and m u ltifo c a l re tin i­ o th e rw is e h e a lth y p a tie n ls a n d i n p a t i e n t s w i t h A E D S . 1 3 - 54

tis, a n d th is r e l a t i o n s h i p h a s b e e n d o c u m e n t e d b y se ve ra l O c u la r and c e n tra l nervous s yste m [C N S ) in vo lv e m e n t

s u b s e q u e n t r e p o r ts (I'ig u r e 1 0 . 0 5 , A —J ). '" и C S D is p r o b ­ t y p ic a lly o c c u r s in c h ild r e n o r y o u n g a d u lt s . [ C l ie n t s w i t h

a b ly a n im p o r ta n t, b u t n o t th e o n ly , c a u se o f t h e c lin ic a l C N S In v o lv e m e n t m a y m a n ife s t c o n v u ls io n s a n d fe ve r in

syn d ro m e o f s e lf-lim ite d a c u te id io p a lh ic m u llild c a l re ti­ a p p r o x i m a t e l y 3 0 ^ o f cases a n d n e u r o r e l i n i t i s in 30 —1 5 T-t.

n itis and n e u ro re lin itis (I'ig u r e Ю .0 5 , A —1 ) (see E .e b e r s o f c a s e s . iA S p o n t a n e o u s r e c o v e r y o f v i s i o n a n d n e u ro E o g ic

id io p a th ic sle lla te n e u ro n e lin itis r C h a p te r 15. p. 12 7S ). d e fic its o c c u r s i n n e a r ly a ll cases, u s u a lly w i t h i n 3 m o n t h s .

O c c a s io n a lly severe o c c lu s iv e v a s c u litis W ith in vo lv e m e n t B i o p s y o f cn la r g e d ly m p h nodes m ay reveal e vid e n c e o f

o f b o th a r t e r i e s a n d v e i n s c a n b e s e e n . ' 1"' A e a s e o f u n i l a t ­ th e in fe c tio n . T h e b a c illu s m ay be d e m o n s tra te d by th e

eral e le v a te d i n tr a o c u la r p r e s s u r e a s s o c ia te d w i l h a n te rio r W a r t h iii- S t a r r y s la in o r c u ltu re fr o m s k ill o r l y m p h node

s y n e c h ia e s e c o n d a r y l o p o s s ib le i n v o l v e m e n t o f th e a n g le s p e c im e n s . D e t e c t i o n o f a n t ib o d ie s to th e c a t-sc ra tc h b a c il­

stru ctu res fro m C S I> has been d o c u m e n t e d . 11 is o la te d lu s is h e lp fu l in lh e d ia g n o s is .'1 4 1Ъ е in d ire c t flu o re s ­

o p tic d is c n e o v a s c u la r iz a tio n w i t h o u t e v id e n c e o f re tin a l c e n t a n t i b o d y a s s a y f o r Е л П п п е Н и henselae a n d ft. ^ ш л г ^ л и ,

is c h e m ia in o n e p a tie n l h y p o th e s ize s th e p re d ile c tio n of a v a ila b le th ro u g h th e te n te rs fo r D is e a s e C o n tro l and

Lh e b a c illu s to m u l t i p l y i n v a s c u la r e n d o t h e l i u m a n d re s u lt P re v e n tio n (C D C ) in A tla n ta , is s e n s i t i v e f o r t h e d i a g n o ­

in in f l a m m a l o r y n e o v a s c u l a r i m ! i o n . ” s is o f C S D . - " 1' ' I l t e f a v o r a b l e p r o g n o s i s w i t h o u t t r e a t m e n t

m a k e s № a S u ^ E l D n o f t r e a t m e n t w i t h d o x y c y c l in e- c i p r o f l o x ­ I f<.05 Bartan vita n^urore liniti sL
a c in , a n d p r e d n is o n e d iffic u lt.
A to H : This 25-year-ald w om an presented with л 2-w eek
]Ъ е te n d e n cy fo r s o m e o f t h e re tin a E a n d o p tic n e rve Icjk of vision in ihe ri^bL eve. 1 week following a level. ih e
in fla m m a to ry Le sio n s to appear v e ry v a s c u la r b io - owned 1wo CliLss. IjliI denied л lick or scMlch. Her visual acu ­
m ic r o s c o p ic a l ly and a n g io g ra p h ic a lly m ay be an im p o r­ ity was 2 & 2 0 0 in the rig hi eye <ind 2CV20 in the left eye. The
tan t fe a tu re o f c a t-sc ra tc h in fe c tio n [F ig u re 1 0 .0 4 , |-L). rit^il eye showed disc edema, dilated vessels M l ihe disc s-ur-
A n g io m a lik t’ m a s s e s re fe rre d t o as e p i t h e l i o i d a n g io m a ­ fncu, and я perfect lipid s-lar in Ihe macula; the le-fl eye had
я small line of I mid 1етром1 Lo Ihe disc. О С Г of the? ri^hl
to sis a n d c a u s e d b y th e c a t-s c r a tc h b a c i l l u s h a v e o c c u r r e d
macula showed retinal edem a and ini m retina I lipid in the
on ih e s k in and m ucous m e m bra ne s of p a tie n ts w ith
ouler p leu i form layer isrnm-i and suhrelinal fluid with pre­
A IL > 5 s . u ' ---------- - in th es e p a tie n ls th e le sio n s m ay appear
tipi tales. She was Healed with azithrornyt'jtli dose puck i^iven
c lin ic a lly s im ila r to K a p o s i's sarcom a. In th e eye (h e the significant loss o f vision. Her Bartonefia Liter was positive
le sio n s m ay s im u la te c a p illa ry a n g io m a s or a s tro c y tic 1:256. Hef vision in the right eye improved Lo 2Q?25 hy 4
h a m a r t o m a s o f i h e r e t i n a ( H g t i f t f 1 0 . 0 4 , L - L ) . T r e a t m e n t is ivionLhs and JU/20 Ljv 9 monlhs w ilh com plele resoiulion of
in d ic a te d o n l y fo r th o s e w i l h s ig n ific a n t lo ss o f v is io n o r lipid iH).

when a s s o c ia te d w ilh th e im m u n o c o m p ro m is e d s ta te as
in p a tie n Ls w i t h Л Ш 5 . T h e o r g a n is m is s u s c e p t i b l e t o s e v ­
e ral a n tib io tic s I n c l u d i n g t r i m e t h o p r i m a n d s u l f a m e t h o x a ­
zo le , rifa m p in [r tfa m p ic in ).. a zith ro m y c in , d o x y c y c l Side?
c ip ro flo xa c in a n d o th e rs .
LYME B O R R E L IO S IS 1 0 .0 6 L y m e d ise a se ^

A to F: Iritis.. vitritis, snow-tjanlc exudates on the pars plana,

I.у m e b o rre lio s is is a tic k -tia n s m ilte d d is o rd e r caused Lysloid macular edema, isnd retinitis prctli Terms biLiterally in
b y t h e s p i r o c h e t e B o rre lia fc u i j j r i m / e r i c a r r i e d b y i h e h m J c j я 25-year-old rman w ilh serologic. evidence of Lvnn* disease.
t i c k , [ h e c] i n Led] c o u r s e is b e l i e v e d l o o c c u r i n t h r e e s t a g e s ;
Le p to s p iro s is .
e a rly, d i s s e m i m ate d and c h r o n i c . te ‘ t h i s d is o rd e r u s u a lly
G and H : tatienL with panuveilis secondary to leptospirosis
b e g in s w it h a c h a ra c te ris tic e x p a t id in g red m a c u lo p a p u -
w ilh deVist v iIriliь and fornTation of vitreous membranes It!'.
Ear a n n u l a r s k i n le s io n . A fte r se ve ra l w e e ks th e o rg a n is m
beploifflra Liveilin n another paLient -iviIh hypopyon mimitk-
m a y sp re a d s y s te n jlta lly und b e a s s o c ia te d w i t h second­ ing er>doph-thiilnniliH (H).
a ry a n n u la r s k in le s io n s , m e n in g itis , c ra n ia l o r p e rip h e ra l
l A - V Ir o i n i-iin L h t'T j I . ,lJ: C.1 a n d H , c t i U r l b y D r S . H . R j t h i n a m
n e u ritis , m ig r a to r y m u s c u lo s k e le ta l p a i n , a n d c a rd itis . T h e
e a rly a n d d is s e m in a te d stag es are cau sed d ire c tly by th e
o rg a n is m s 'Ih e p a tie n t o fte n does not re ca ll a tic k b ite . Jte tin a l a n d c h o r o i d a l in filtra tiv e i n v o l v e m e n t o r e x u d a tiv e
M o n th s t o y e a rs la te r, i n t e r m i t t e n t o r c h r o n i c a r th r itis , o r r e t i n a l d e l a c h n t e n t is n o t s e e n . O p t i c n e u ritis a n d n eu ro -
c h ro n ic n e u ro lo g ic or s k in a b n o rm a litie s m ay d e v e lo p , re tin ilis c a n b e se e n . A n t e r io r u ve itis c a n b e in s id io u s , u n i ­
i h e c h r o n i c s ta g e is i m m u n o l o g i c a l l y m e d i a t e d w i t h d e p o ­ la te ra l, o r b ila te ra l, a n d m a y recur. O c c a s io n a ll y h y p o p y o n
s itio n o f im m u n e c o m p le x e s . is s e e n i n t h e a n t e r i o r c h a m b e r ( I ' i g u r e 1 0 . 0 6 , E l ) .
A m is c e lla n e o u s g r o u p o f f u n d u t p ic tu re s - in c lu d in g S y s t e m i c l e p t o s p i r o s i s is a z o o n o t i c s y s t e m i c i n f e c t i o u s
pars p la n itis , re tin a E v a s c u litis , b ila te ra l d iffu s e c h o r o id itis , d i s e a s e c a u s e d b y a s p i r o c h e t e l.e p lc s p irn . I L is a f e b r i L e i l l ­
a c u te p o s te r io r m u lt if o c a l p la c o id p ig m e n t e p ith e L io p a th y , ness a s s o c ia te d w ith ja u n d ic e , h em orrhages, and renal
m a c u l a r e d e m a , p a p i l l e d e m a , a n d L e b e r 's s t e l la t e n e u r o p a ­ fa ilu re . I h i s c lin ic a l p ic tu re w a s first d e s c r i b e d in 1SS6
th y , c ra n ia l n e r v e p a ls ie s [s p e c ific a lly a b d u c e n s n e r v e ) , a n d b y A d o lf W e ilr he nce th e nam e W e il's d is e a s e . A l t h o u g h
o p tic n e u ritis - haw been re p o rte d in p a tie n ts w ith sys- rats are th e com m on re s e rv o ir m ic e . c a tU e r p ig s. dog£.
L e m ic illn e s s a n d s e r o lo g ic e v id e n c e o f p r e v i o u s e x p o s u r e and o th e r w ild a n im a ls can a ls o harbor th e o rg a n is m .
L o B . b u rg d o rfe ri . 13 : 'J O f t e n t h e V E n e r v e p a l s y is s e c o n d a r y Ih e u r in e o f Lbe in fe c te d h o s t tr a n s m its ih e b a c te ria . Ih e
to ra ise d in tra c ra n ia l pressure; h o w e v e r is o la te d in vo lv e ­ o rg a n is m s can liv e in a lk a lin e so il and w a te r fo r a fe w
m e n t w i t h o u t e v i d e n c e o f i n t r a c r a n i a l h y p e r t e n s i o n is s e e n weeks. Lept&spirtf e n t e r s Lbe b o d y t h r o u g h b r o k e n s k in a n d
o c c a s io n a lly . K e ra titis , c o n ju n c t iv i l i s r e p is c le ritis , p o s t e r io r m ucous m em brane. M u Eli p l i c a t i o n and h e m a to g e n o u s
s c le ritis, a n d a n te rio r u v e itis are o th e r o c u la r m a n ife s ta ­ spread re su lts in th e in v o lv e m e n t o f v a rio u s o rg a n s . Ih e
tio n s . O n l y p a rs p la n ilis a s s o c ia te d w i t h s n o w -b a n k exu­ s e v e r i t y o f t h e d i s e a s e is h i g h l y v a r i a b l e f r o m m i l d t o fa ta l
d a tes, a n d a n te r io r u ve itis , how ever, have o ccu rred w ith d ise a se . Ja u n d ic e due Lo h e p a l i c in vo lv e m e n t is s e e n in
s u ffic ie n t fr e q u e n c y t o suggesL a s ig n ific a n t r e la tio n s h ip to 1 0 - 1 3 % ; renaE i n v o l v e m e n t w i t h r e n a l f a i l u r e is t h e c a u s e
l .y m e d ise a se (H g u re 1 0 . 0 6 , A ^ I ^ 5Jr5a,6D O c u l a r in vo lv e ­ o f d e a th in m o s L fa ta l cases. In te n s e headache, m y a lg ia ,
m e n t i n s y s t e m i c b o r n e ! i o s i s is n o t v e i y c o m m o n , t h e i n c i ­ m u s c le te n d e rn e s s in v o lv in g th e caEves and th e lu m b a r
d e n ce b e in g a p p ro x im a te ly 1 - 4 % . T re a tm e n t is w i t h oral re g io n , ic te ru s , m e n in g e a l irriLa tio n r d e liriu m /p s y c h o s is ,
d o x y c v c lin e o r in tra v e n o u s c e ftria xo n e fo r 2 -3 weeks in a n u ria o r o lig u ria , m u llio rg a n h e m o r r h a g e s ., a n d c a rd ia c
a d d itio n l o c o rtic o s te ro id s . a rrh y th m ia or fa ilu re can a ll b e p r e s e n t i n g s i g n s / ’0 ] h i s
c lin ic a l p ic tu re c a n m i m i c o t h e r in fe c tio u s fe ve rs se e n in

L E P T O S P IR O S IS _______________________ (h e tro p ic s such as in flu e n z a , dengue, m a la ria , ty p h o id ,

vira l h e p a titis , ric k e tts ia l d ise a se - m e n in g itis , re la p s in g
O c u l a r le p to s p ir o s is c a n p r e s e n L in b o t h th e in fe c tive a n d fevetr a n d e n c e p h a l i t i s .
i m m u n o l o g i c stag e o f s y s te m ic le p to s p ir o s is . A m a j o r i t y o f ih e d ia g n o s is can be c o n firm e d by th e m ic ro s c o p ic
cases p re s e n t as acute o r s u b a c u t e a n te r io r n o n g r a n u E o n ia - a g g lu tin a tio n te st { . M W ) fo r le p to s p iro s is or by PCR of
to u s u ve itis o r p a n u v e itis . L 'h e o n s e t a n d s e v e r i t y a r e v a r i ­ a q u e o u s o r v i t r e o u s f l u i d . ...........rt C l i n i c a l l y t h e d i s e a s e h a s t o
a b le a n d d o n o t c o rre la te w i t h s y s te m ic s e ve rity. T h e o c u la r be d iffe re n tia te d fr o m o th e r causes o f n o n g r a n u lo m a to u s
fe a tu re s c a n a p p e a r s e v e ra l w e e k s a fte r th e s y s te m ic illn e s s , a n te rio r u ve itis , e n d o p h th a lm itis , Ee h ^ e fs d is e a s e , sar­
hence th e d iffic u lty and d e la y in d ia g n o s is . Un3ess one c o id . a n d c a n d id ia s is . J .e p lo s p ir o s is c a n b e se e n w o r l d w i d e
has a h ig h in d e x o f s u s p ic io n i t is o f t e n m is d ia g n o s e d as th o u g h i t is m o r e c o m m o n in th e tro p ic s . O c u l a r i n v o l w -
id io p a th ic P a n u v e i L i s is u s u a l l y s e v e r e , a c u t e , m e n L va rie s fro m 3 % to 9 2 % in th e tro p ic s , 10 -4 4 ^ in
a n d r e l a p s i n g , a n d is c h a r a c t e r i z e d b y m e m b r a n o u s v i t r i t i s Hu rope, a n d 2 % in Lh e U n i t e d S ta te s .
a n d v a s c u litis , m o s t ly a ffe c tin g th e v e in s . R e tin a l v a s c u la r Tre a tm e n t of th e s yste m ic illn e s s in its acute stage
o c c lu s io n a n d n e o v a s c u la r iz a t io n a re rare. V it r e o u s i n f l a m ­ in v o lv e s th e use o f a n tib io tic s su c h as p e n i c i l l i n , a m o x i ­
m a tio n is f i b r i n o i d w ith c lu m p s o f vitre o u s c e lls o f t e n c illin . d o xy c y c lin e , or c e ftria xo n e . T h e u ve itis is LreaLed
arranged in a s trin g o f p e a rls s im ila r to G e n d in a viiritis b y t o p i c a l , s u b - E'en o n , o r o r a l s t e r o i d s d e p e n d i n g on th e
( E 'ig u r e 10.06. G ). It is o f t e n m i s t a k e n f o r e n d o p h t h a l m i t i s . e x t e n t o f i n v o l v e m e n t a n d c y c l o p l e g i c s . ^ 0,1'
 LeptobyiruFiB 8 I ■

р '
 lO.Oj Luetic chorioretinitis.
L U E T IC C H O R IO R E T I N I T I S
A lo F: Acute? poslerior placoid chorioretinilis in both eyes
M any d iffe re n t fu n d u s ie s io n s have been d e s c rib e d in a i this 42-year-old homosexual man with a 2 -week history
c o n s e n t La! and A c q u ire d s y p ttlU s (FEg p fe s L 0 .0 7 - J 0 .ll) . of blurred vision Lind ГЬолl<drs- in Eiolh eyes. Approximately
S a lt-a n d -p e p p e r changes a ffe c tin g pri m a riLy th e p e rip h ­ wtieks previously he had nok>d a s-kin enJptjan on lhe sole of
e ral re tin a are th e m u s t fr e q u e n t a lte r a tio n s d e s c r ib e d w i t h his left loot and perirectal pruritus. Visual acuily was 2(1/20
c o n g e n ita ! s y p h ilis . S e ve re i n v o lv e m e n t o f th e o c u la r f u n ­ in Ihe ri^ht eye anej 20/30 :n the lefl eve. There wag e v i­
dence of bilateral anlerior and pobtdetip uveilis, with many
d u s , h o w e v e r, m a y o c c u r a n d p ro d u c e a p ic tu re s im u la tin g
vilreous c e lIы and opacilies in the left eye (A . ilecaune of
ret In i Its p i g m e n t o s a (Fig u re 10 ] ] r t and F ) . En a c q u i r e d
the presence of irregular retinal whitening in the periphery
s y p h ilis * p a r tic u la r ly i n p a tie n ts w it h s e c o n d a ry s y p h ilis ,
oE the iel't eye, a diagnosis bf possible acule relinal necro­
several a c u te fu n d o s c o p ic p ic tu re s s h o u ld suggest th e p o s ­ sis was made. Four w w k s Liter he noted marked visual Ions
s i b i l i t y o f s y p h i l i s . S e c o n d a r y s y p h i l i s o c c u r s <S w e e k s l o & rn [he right eye. VisuaF acuily was ЗЛОО. There w ere several
m o n th s a fte r th e p r i m a r y i n o c u l a t i o n , w h ic h p a rtic u la rly large zones of gray-white change at the level of the FiPb
in h o m o s e x u a ls m a y be o v e rlo o k e d . D u rin g th e s e c o n d ­
and outer rrfina in Lhe m acula L3 anti periphery : 0 or the
ri^hl eye. Angiography !L> and E) reveated these lesions lo be
a r y s t a g e o f s y p h i l i s t h e r e is w i d e s p r e a d d i s s e m i n a t i o n of
hypofluonescent ta rly and to stain laler. A eopard-spot pat-
Lbe s p iro c h e te s , and th e p a tie n t o fte n e xp e rie n c e s m a l­
Lem of bnckfjround hypo fluorescence was apparent in the
a is e , fe ve r, h a ir lo s s , p a p u la r m a c u la r ra sh , c o n d y lo m a macutar area iD j. The blood and cerebrospinal fluid serology
la ta , m u c o u s p a tc h e s , and g e n e ra lize d ly m p h a d e n o p a lh y were positive for syphilis. Following IV penicillin, Ihe fun-
( E 'ig u r e s 5 0 .0 7 , Ю .U , J and K}. A p p ro x im a te ly 5% d u ; changes and uveitis cleared promptly, leaving л coarsely
o f p a tie n ts w ith secondary s y p h ilis w ill show e vid e n c e mol Iled pattern of pigmentation in lh e macular area. He
of p a n u v e itis .'1 J p ro b a b ly th e m ost com m on fu n d u s experienced n rapid recovery of vision. Four months later Elis
visual acu ily was 20/15 in lht1 right eyu and 20/20 in the left
change is t h a t o f v i t r e o u s c e llu la r i n f i l t r a t i o n and e ith e r
eye. There was mild pigment mottling in both macuEar areas.
s in g le o r m u llip le r n o n e le v a te d { p E a c o id J, g e o g ra p h ic , y e l­
G Lo I: Acute posterior piacoirl cEnjrioretinilis.. vilrilis, and
lo w -w h ite . ill-d e fa n e d r c h o rio re tin a l le s io n s th a t o fte n
macuEopapular dermatitis caused by secondary syphiTis in a
are c o n f l u e n t i n th e p o s te rio r p o le a n d m id p e rip h e ry o f 4S-year-ord man whose visual acuily was b/200. Fluorescein
th e fu n d u s (Fig u re s 1 0 .0 7 , H a n d G ; 10 10. H ; H illy [ and an^io^aphy revealed a leopard-spot patlern of non fluores­
L ] . 73-65 B o l h e y e s a r e a f f e c t e d i n h a l f o f a l l c a s e s . I n s o m e cence in Ihe area of partial fading o f Ihe gray-white lesion
p a tie n ls th e c h o r io r e tin a l le s io n s m a y b e la rg e ly c o n fin e d
that was nonfIuor-escenl early and stained Late (H and It.
FHis lefl eve became involved -several days later. The lesions
to th e a re a a r o u n d th e o p t i c d isc . I h e y m a y b e a s s o c ia te d
resolved promptly after treatmenl witii punicjJIin and his
w ilh s u p e rfic ia l, fla m e -s h a p e d h e m o r r h a g e s . rl ' h e fu n d u s
acuity returned lo 20.-'.30 in lhe righl eye nnd 21У20 in lh e lefl
p ic tu r e m a y s i m u l a t e t h e e a rly stages o f t h e a c u te re tin a l eye w ilh in 4 wcieks.
n e c ro s is syn d rom e. ' " ' 1 Secondary re tin a l d e ta c h m e n t ] to L:1Alopecia ■|■, and m aculopapular denrtaBtis 'K and 1:
and c h o ro id a l d e ta c h m e n t d e v e lo p hi som e p a tie n ts ." in palienls With acute visual 1(»ьн associaled w ilh acuLe posle-
Jlie a c tiv e y e l l o w - g r a y p la c o id o u t e r re tin a l a n d c h o r o id a l ■:or placoin choriorelinilis cnuued b y secondary syphilis.
le sio n s fa d e c e n tra lly , a n d o f t e n t h e r e is c l u m p i n g o f t h e hLj - K f r a i l C jit a l'I ii 1 Iroin K im o .uirl K jo iciitM u m '■

R P t in a le o p a rd -s p o L c o n fig u r a tio n { E :i g u r e s 1 0 .0 7 r D r IE,

and [; 1 0 . 1 0 ) . :'u I h e s e p ig m e n t c lu m p s m ay becom e le s s
a p p a re n t o ve r a p e rio d o f m o n th s . T h e c l i n i c a l c o u r s e is
va ria b le . In s o m e cases ih e c h o r io r e tin itis re s o lve s spon­ ]’ l u o r e s c e i n a n g io g ra p h y in th e re g io n of th e a c tiv e
ta n e o u s ly , a n d th e a p p e a ra n ce o f th e fu n d u s a n d re tin a l y e lto w -w h ite c h o rio re tin a l le sio n s in itia lly shows e vi­
fu n c tio n m a y re tu r n to n e a r n o r m a l . In o t h e r s w i d e s p r e a d dence o f h y p o flu o re s c e n c e , fo llo w e d by la te s ta in in g
areas o f c h o rio re tin a l a tro p h y and lo ss o f re tin a l fu n c ­ at Lhe level o f lh e ItP E ( E :i g u r e 1 0 .0 7 , [J, E, H r and I).
t i o n o c c u r [E 'ig u r e 1 0 . 1 1 , A - С ) . M i g r a t i o n o f R P L i n t o i h e ] :! u o r e s c e i t i s ta iitittg o f th e o p tic d isc n U id m a jo r re tin a l
o v e r ! y i n g re tin a in a b o n e - s p ic u E e p a tt e r n m a y o c c u r m a n y v e i n s is f r e q u e n t . D u r i n g t h e e a r l y s t a g e s o f r e s o l u t i o n o f
m o n t h s la te r. C h o r o i d a l n e o v a s c u l a r i z a t i o n d e v e l o p i n g a t t h e a c tiv e c h o rio re tin a l le s io n s , th e le o p a rd -s p o t change
th e e d g e o f a c h o r i o r e t i n a l sca r m a y b e a la te c o m p l i c a t i o n in th e R H : m ay be m ore a p p a re n t a n g io g ra p h ic a lly th a n
[ E - 'i g u r e 3 0 . 1 1 , D J , i o p h l h a ! m o s c o p i c a l Ey.
 Lactic CitohoretiiiifiB 81

b
 The a c u te p la c o id c h o rio re tin a l le s io n s of secondary 10.08 Syp hi Iitic jnner re Lrni Ii s and vascul ilis.
s y p h ilis m a y b e m is ta k e n fo r th o s e o f acute p la c o id m u l­
A Id С : Л 2fl-yeAr-o]d H ispanic man noLed blurring of vision
tifo c a l p ig m e n t e p ilb e lio p a th y a n d s e rp ig in o u s c h o ro id i­ in hiч left eye 1 day after л dental procedure. He was (Й1
t i s , ' 41'1 I i ] t e l l i n g a h i s t o r y a n d / o r t h e d e t e c t i o n o f a n y o f t h e amoxicil in and m ico n aio le. H e presented a w eek later чл-il К
n o n o c u la r m a n ife s ta tio n s o f s e c o n d a r y s y p h ilis , a n d in sti­ fi vision of 2tl/20 on lbe right and G/30 on Lhe left. There

t u t i o n o f p r o m p t t r e a t m e n t w i t h p e n l d j t l n , is i m p o r t a n t i n were numerous keratic precipilales, anterior cham ber cell

m a k i n g th e correct d ia g n o s is a n d in p r e v e n tin g p e r m a n e n t and flare, Koeppe iris nodules., And anterior vitreous tells.
1liere w ere t о Ilet Lion? ot w h ile util is on Lhe posterior hya­
v i s u a l lo ss. R e t u r n o f v i s u a l f u n c t i o n m a y b e d r a m a t i c . T h e
loid temporal to the т л е ula and in Lhe inferior vitreous; base
p a tie n t s h o u ld b e e v a lu a te d fo r e v id e n c e o f A I D S , w h ic h
(A and D ). The inPerolemporal relinal vessels showed w hiten­
o fte n a c c o m p a n ie s secondary l u e s . " 1" ''' S yp h ilis m ay
ing ol (heir walls (B and CJ. H e was HIV-positive and blood
be a c e e le ra le d and n e u ro s y p h ilis e n c o u n te re d e a rlie r in and cerebrospina:I fluid rapid plasma reAgin [C5F RL3K' were
p a tie n ts w i l h A ] grossly elevAled. He received IV penicillin for 1-1 days, foE-
I n t h e p a s t 5 y e a rs th e re h a v e b e e n several cases o f o c u la r Eowrng w hich signs and symptoms- resoFved w ith reLurn of
s y p h ilis w ilh a sp e c ific c lin ic a l p re s e llta llo л L b ^ l re s e m b le s
vition Iо 20/23 and gradual melling off of Lhe w hite coll!; of
Lhe retina and Lhe vessel waMs.
acuLe re tin a ! n e c ro s is , m o s l o ft e n se e n h i h o m o s e x u a l a n d
H to L: This 44-year-old Caucasian man presented w ith cys-
h e te ro s e x u a l m e n w h o h a ve sex ^ 'ith m e n fin d ­
Loid fnaculaf еЙегтЦ and a vision of 1 0 /2 5 . Fluorescein was
in g s in c lu d e a c h a ra c te ris tic ground g la s s appearance of unremarkable except for dye accum ulation in the cysts iHf.
m u ltifo c a l w h itis h le sio n s p re se n t in (h e in n e r re tin a a n d Hu was treated w ilh one inLravilneal injection ol Lri am с ino-
at t h e p re n e tin a l l e v e l a s s o c ia te d w i t h o c c lu s iv e v a s c u litis o f lone, and vibion improved and the macular edema resolved,
t h e v e s s e l s i n t h e i r v i c i n i t y 1' " : " ,B ( f i g u r e s Ш .O S , Hr D . and lw o monll:s taler he noled recurrence d|f the visual blur in
I; 1 0 .0 9 , П - J J . l h e i n n e r re tin a l a n d p re re lin a l c o lle c tio n , the riyhL eyer and returned after a further 2 monlhs w ith
count fingers vision; several areas of ргегеИпдГ collection of
a lo n g w it h th e p e riv a s c u la r in filtr a tio n , re s o lve w ilh tre at­
White cells, And vasriilaF narrowing I Angiogram showed
m ent (fig u re s 1 0 .0 Й , E - G and K; 1 0 .0 9 , M and N ). ih ls
leopard-spot pigment change i| and К . His V D K L was posi­
p r e s e n t a t i o n is n o w seen In n e a rly 3 5 % o f cases o f o c u la r
tive And H IV was negative. He recetoed IV p^jii.cJMin for 21
s y p h ilis , w ilh t h e p l a c o i d l e s i o n m a k i n g Lip a n o t h e r t h i r d ., days, E>uL vision remained poor due to oplic Atrophy and
and th e re m a in in g (h ird a cco u n te d fo r by n o n s p e c ific arterial occlusion IL :.
a n te rio r u ve itis, d isc e d e m a ., v a s c u litis , a n d o t h e r le s io n s iCjuurtesy: A-Li, LJr Kiulint-Merrill. li-L, IJf Ivjin BnEllc. I, Aliu-rVjnnUi^i..
[fig u re s 10.09, O-X; 10.10, A -G). W h e th e r d iffe re n t sero­ I Jiwmtficc 5.. lhu KHin.il At]J i -■iiun,:k r-. 2P Id, 47itJl-7(>20-^.520-'J,
|?.14fl.|
t y p e s o f Tre p o ne m a p a llid u m c a u s e d i f f e r e n t c l i n i c a l m a n i f e s ­
t a t i o n s is L h e e x p l a n a t i o n o f t h e d i v e r s e m a n i f e s t a t i o n s i s
not know n.
 In some pAlients with Acquired syphilis the fundus
picture ti primarily thal of relinaE VAseulitis wilh reti­
na] hemorrhages/l,lHI,,H6,?!f‘ ]Q3 occlusive arterial disease,
and retinitis proliferans (see Mgure 10.1J, G and i 3 _ :"1
Many different fundoscopic changes have been ,ittrib-
Lited lo syphilis,, including neurorelinili3r'0j disciform
scar, acute retinal necrosis,B5 pseudo-retinitis pigmen­
tosa, Kyrieleis' plAques,"01' and optic atrophy.1'1' Syphilis
has been called lhe 'great imitator?'"1 Anterior segment
involvement wilh a syphilitic gumma (I'igure 10.10,. G)
presents with an iris nriAss. It is often difficult Lo deter­
mine lhe stage of syphilis bated on the ocular findings,
Lhough most inflammatory presenLAlions o f syphilis occur
in the secondAiy stage. Similar findings have been seen in
patients with neurosyphilis, tertiary syphilis, and latent
syphilis.1'1'* ihe incidence of syphilis has been on lhe rise
since 2000 with a 33.5% increase noted between 2000
and 2004. Several outbreaks haw been reported from New
York City, Miami-Dade County Washington, Houston, San
l:rancisco. and Southern CAliforniA. A CL>C analysis esti­
mates that 64% of the early stage syphilis cases in 2004
were in M SM compared to 5 % in 1999.
Since it is a common infection, however, care must be
used in assigning it as the cause of an ocular disease solely
on the basis of positive serologic tests for syphilis, ibese
include the nonspecific reagin tests, such as VDftL, or
more specific tests, including fluorescent treponemal anti-
body-Absurplion (FJA-Abs) and microhemAgglutinAtion
assay-lY e p o ф п ш fjjb lt id u m (Mi EA-TET). There is some contro­
versy concerning the criteria for diAgnosis of neurosvphilis
and for the dosage And route of administration of penicil­
lin in these patients.'1'' Because d f ihe high incidence o f
positive reaction o f the cerebrospinal fluid (CSI:J Lo the
serologic tests for syphilis during the secondary stages
o f the disease, CSF examination is usually not recom­
mended for patients presenting with the ocular mAnifestA­
tions of secondAry syphilis. JJecommended Treatment for
10.09 Syp hi Iitic placoi d с ho rio re I t n t t i s nnct retinitis.
А to IV A 65-year-old diaboLic and hypertensive man
refiorlcd а I -day sudden visu.il lots; Lo 20/tiO in his lefl
eye. There was an afferent papillary deJecL but no anterior
chamber or vitreous cells. fla c c id lesions al tbe level o f I be
choroid or pigment epil helium w ilh a tew biol relinal hem­
orrhages w ere nobed in the lefl eye (Ё). Angiogram showed
mild late irregular hyperfluorescence of tbe placoid lesion
(Cl. A diagnosis of" 'choroidal ischemia' was made; carol id
and cardiac echo w ere normal. His vision declined to
2 ti/130 a I wetik T w hen oral prednisone was begun at 40 mg
per day. AL w eek 2 the vision worsened in his righl eye and
did not improve in his JofL. The righl eye now had placoid
lesions w hile tliu lesions in the lefl eye had faded D and Ё..
Ал angiogram showed Iл In hyperfl uorescence of Ihe placoid
lotion in both eyes- (F and C j. O ral prednisone w as int reased
Lo lOOm g per dav and JaboiaLorv tesls were ordered. He
skipped his appointment and returned after a w eek with a
drop in vision lo hand motions in his- right eye and 2Q/tuO In
the lefl. H e n o w had sevieral focal areas of superficial reLinal
whiLening and vascular narrowing in bolh eyes in addition to
the plairoid lesion lhal had eMended under Lhe loved in the
rig|iL ey® (H-Jt. An angiogram showed early blocked fluores­
cence of Ihe placoid lesion w ilh Iale slain ing and leopard-
spoL change (K and Lj. R PR and FTA-Abs reLurned posilive.
patiems wilh active chorioretinal diseAse caused by syphi­
lis is aqueous crystalline penicillin С ( ]fl-24 million LJ [V
daily) or procaine penicillin (2.4 million LJ JM daily) with
oral probenecid (500 mg four limes daily) for JO -14 days.
]f CSF pleocytosis has been no Led, these patienls should
be monitored al 6-monthly intervals with CSF studies
until the cell count normalises. In patients allergic lo peni­
cillin, IV or LM ceflriavone (2g per day for 10-14 days) can
be used.11 All patienls with syphilis should be tested for
J ![V status and the treatment in EliV-positive patients lasts
for 3 weeks. 'Ibose who are HIV-positive should be m oni­
tored for treatmcnl failure At 6, 12. IS , And 24 months.
iiu'rrL' СЗкпЦ>геИiritis 8.23
E IJ. (I^ C o n tin u e d

He reporled several inlemet J a in at partners over 1 yeart fol­

lowing ihe dealh of his wife from cancer. He was hospital­
ised and received 2 m illion unilt every -Ih of IV ciystaHjma
penicillin fallow ed by Ьеплэ1Ыпе p e n ic i'!ii: £ 2 . 4 m illion
uniLs [M for 3- weeks. All w hile and placoid Itiiions- resolved
with leiidunil ygsc-uls r^ ira y i/ l ng iM and N'i.
О t p X : A -t4-year-old Hispanic wom an had several months
of declining vision ir both eyes associated with some pain
around the eyes. Htir daughter reported that the molber's
personality h-ad recently changed: she had becom e shorl
tempered and forgetful. Her besl corroded visual acuity Was
20/ft0 on the rijqJnL and Ю !2 ъ сиг the lefL. then? w ere 2-3 +-
vilreous cells in bolh eyes. 5ihe htid had л w hole imdy rash
15 years prior and had Iw a lifetime sexual partners. Etolh
up] к discs w ere awe I Jen with dilated telangiectatic vessels
on I heir surface Ю and F1). There were old inactive perivas­
cular chorioretinal scars in both eyes in ihe mid periphery (Q
and Kj. The red-free images showed the abnormal disc ves­
sel s beLter (5 and '14 Angiogram delinealed the dilated ves­
sels over lh-е disc and surrounding relina early, which leaked
profusely in the mid and lale phases (U —W j, The peripheral
chorioretinal scars showed staining of the ed^es with no new
activity fX). Further history rdMealed her firsl partner had a
sore on his penis 15 y e a li a^o,. after which she had devel­
oped ihe w hole body rash Lhal resolved With no sequelae.
Sbe had fell normal cm Li] recently witli the ctn.se! al visual
blur -and p erso nally change. Her К ГК was negative but her
Jreptm em ii p a llid u m particle ag|i|;ilinalion (ТРРА) lest was
positive, confirming a diagnosis of tertiary syphilis. She
received 24 million uniLs of IV penicillin for 14 days. A l 3
week.1- her vision had improved Ic 20.'50 on ihe righl anti
remained al 2 0 /1 5 on I he letl. Нет persona lily reLurned lo
normal.

ir .u u r t L - iy : A - M , I h JiJ f fid M p U t - v r O - X , [ J r I c f f r ^ v W h iC L 'h L u r F . i J , F . . R . V .

A i m . V . m n u j L i . L,iyy nt'ti-: и J., I l i t 1 Ь!г:1шл1 Л И .ьь. !?-,iu n d e rs i ' J h J , Ч г -tVM-
7tl2 0 -i3 2 U -n .
iiu'rrL' ChnripTetiiiitiB tl^iS
If) .10 Sy] j hi Iitic о piic neu ri (isi

A [o F: This 58-year-old elementary school Leacber woke up

with a circular yellow light in her cemral vision. Visual acu ­
ity was 10/20 in both eyes. Anterior segment was normal.
A Hum phrey visual field showed an enlarged L?Iiгьс.1 spy* in
ihe? ri^bt eye. lb e righL fundus showed a swollen optic disc.
(A and Bl and the left w as normal 1C). An M R I ol lbe brain
and orbits revealed no abnormalities. Observation was rec­
ommended, and a 1esl for syphilis returned posilive.. as
did her husband's ^ubsequenLly. Visual acuily dropped 1o
20/40 in ihe ri^lit eye, the disc edem a persisted (D), and
an angiogram shejwed dilated vessel-s on ils surface (Eh. ih e
was desensi tizL^ Lo penicillin and treated wiLh 2 weeks of
IV penicillin and do\vi:yclmu. Tbe disc edema impressed i l '
and Ehe visual acuily returned to 20/25 fn lbe ri^hl eye and
remained al 20/20 in ihe left eye.

Syphilitic gumma.
G to L: This 53-yeai-old man presented w ilh a hisLory of
scratching his fefl eye w h ile changing his contact lenses.
H e was diagnosed with a corneal ulcer and ttarled on ^aLi-
floxacin (Zymarl drops. Two weeks laler his visual acuity bad
dropped to hand molions in Ihe lefl eye and he w a t noted lo
have an anlerior chamber ur.i г ulema with blood and drlaLed
iris vessels with posterior synechia and uveitis iGl. Hundus
examination of ihe ri^ht eye revealed a placoid legion in ihe
inferonasal fundus (H i. A fluorescein an^ioyram of this eye
showed late hyperfluorescence (]). A V D R L was done w hich
confirmed syphiliLic д аитта. He was known Lo be I-E1V-
posilive and was on nevirapine iViram unej w ilh a t!U 4 count
ot 2tf!S and an undetectable viral load. His C5F VDRL. was
positive at 1:4 and RPR was posilive al 1 :.512. He was started
on IV penici I tin С every 4h. A w eek Eater his gumma bad
decreased in Size by ball and lbe placoid lesion in ihe fun­
dus had almosl resolved.. leaving mild pigment гтгснЩяд J) . A
fluorescein an^iot;ram done 4 weeks Taler revealed leopard-
spot pigment t паподе al '.he site erf ihe placoid lesion IL' and
complete resolulion of Lhe syphilitic ^umma ;Kl.
iC'uurCLtiy: A-I-. L)r M i f k. Dai lyj Ci-L. LJr (./i ir.'if ti-nrr.j
! Q, M tuetic chorioretinitis.

Д Lo C: Bilateral chorioretinal sCdlfi caused by secondary

luelic chorioreliriitis.
D : SqbretiRil ntitjvatcularikalian (arrow) зп lhe macula of
fi pjflSefll w ilh chori ordinal scara following churiorulinitis
caused by ЁёСогКйгу syphilis.
E and F: Congenital luetic choriorelinopFilhv in а 41-year-
old wom an w ilh poor vision all of her Ijft?, interstitial kera­
titis, positive fluorescent lroponemal an1il>ody ;FTAl, and
2(^'SD visual acuily. NoTe 1he* narrowing (il lhe retinal vessels;
optic disc pEiI lor, and pseudo-retinitis pitfmerrinsa change
peripherally.
G and H : l-’resumed Iue?Liс r d iп-лI vasculitis; in this ГЮ-уеаг-
o|d homosenuaii man w ilh a 10-dny history ul blurred vision
in his rij’hl eye. The left eye was imblydtaiq since birtH. Hive
years, previously he had primary syphilis. SiKJeen months
previously he developed a skin rash on the feel and hands.
Tcfls wns di^Jfiosed as syphilis .3 т о л Ih к q^lore Lhe onsel of
visual symptoms- and he received IM, penici lin. His visual
acuily was 2(A^50 in his ri^h-L eye and hand mol ions only ir>
lhe lefl eye. He had w id ely scattered relinal hemorrhages,
fierivHsci.ilar ел и da Li on Х У , and angiographic evidence of
multiple siLes o f relina] vascular obstruction, predominantly
□fleeting the veins IH h. There w as perivascular starring in lhe
la I e pholoj’ra phs.
J lo L: Klacoid choriorelinili-s in ihis HIV-positive 4.i-year-
uld man w ilh generalized rash over his trunk, abdomen, and
palms. He complained of decreased vision in his fi^ht eye
fur 2 w eeks: visual acuity was 4/20$ in ifie ri^hL and 20/25
in the lell eye. He had a fain] placoid lesion in lhe [eft supe­
rior macula. His C D 4 couni was in Lhe 2 0 0 s and viral load
was Lmdelectable. He was admitted afld received IV penicil­
lin tor 3 Weeks. The placoid lesion appeared much less dis­
tinct within a w eek (Ll and his vision improved to 2 0 /7 0 . He
did not return for lurl her follow Lip.
T U B E R C U L O S IS t fa. i 1 T u b e rc u la r multi f o c a I c h or i oret i n1L i s ,

A lo F: A 30-year-old wom an in India oomprained of insEdi-

live n th o u g h p u lm o n a r y '' and Щ ||р и |ш № т у tu b e rc u ­ ous onset,, gradually progressive Joss Ы vision in [tie left eye
lo s is (Т В ) has b e e n p re v a le n t w o r l d w i d e fo r h u n d re d s o f over I S months. T3ni-s was а уsot iл led w ith pain and redness.
y e a r s ; r e p o r t s o f o c u l a r T li a p a r t f r o m b a le s ' d i-se a s^ h a v e She was iTC'att’d for acute аЫкпог j veil is elsewhere w ilh l.opi-
b e e n m e a g e r u n til th e past 10 y e a r s . T h i s is l i k e l y d u e lo саГ and oral steroids tip lo bOmg per day. ih e was otherwise
Lhe in a b ility to c o n firm ih e d ia g n o s is a c c u ra te ly lac k of healthy. Her vision in Lhe left eye was 2Ch/]00, w ilh anterior
thamb^.jQ&l t and flarfc Jkhe-tjafl several deup choroidal lesions
k n o w le d g e a m o n g th e o p h t h a l m i c p e r s o n n e l in c o u n trie s
in lhe pr^t-Lerior pole w ilh overlying exudative relinal detach­
w ith a h ig h p re v a le n c e o f th e d is o rd e r, a n d Less a c c e s s t o
ment 1A). An angiogram showed early hypofluorescence of
s p e c ia lis e d care in ih e s e c o u n trie s . S e ve ral n e w m a n ife s ta ­
Lhe с Ь о г а Ш lesions and JaLe fiyperm iorestence Iseginning
tio n s o f in tra o c u la r Т Б h a v e b e e n r e p o r t e d . 6^ L ] 2 - l 2 ;| W i t h at Lhe edge of [he lesions and pooling of dye into the sub-
a n i n c r e a s e i n t h e n u m b e r o f H I V p a t i e n t s , o c u l a r ' [ ' I I is o n retin,il spate fB-L3J. ih e had гю conlat.1 wiLh a person wilh
Lhe rise . LM ra p u lm o n a iy i n v o l v e m e n t is s e e n in 5№ Ь o f active tufjerculosis. ManLoux LesL was posilivu at 20 Ъ 23 mm.
p a tie n ts w i l h b o t h Т В a n d A [L > S .
sedimentation rale was 5mrn( thesL S(-r.iy was normal, and
CJu3jmifEfttJN-T6 Gold was positive. 5he received four-diug
T u b e r c u l o s i s is a s y s t e m i c d i s e a s e c a u s e d by А 4 } г а £ ю с 4 о т и З Д
anti-ТВ tf^itiapy aionj" w ilh nOrftg of prednisone And JO mg
[yJwi'LH/psj's a n d is c h a r a c t e r i s e d b y c a s e a i i n g g r a n u l o m a f o r ­
of pyridoxine. Three weeks laLer hew vision had improved to
m a tio n in th e a ffe c te d tissu es. A l t h o u g h p u lm o n a ry Т В is 20/25 and lhe lesions appear pealed lb and 3-..
Lhe c o m m o n e s t m a n ife s ta tio n , e x t r a p u ln io n a iy in v o lv e m e n t G Lo L: A 17-year-old Indian girl w ilh decrease in righL eye
can in c lu d e th e g a s tro in te s tin a l, g e n ito u rin a ry c a rd io va s ­ vision [or 3 months [amounting ling и аЕ 3 meters and a rela­
cu lar, s k in a n d c e n tra l n e r v o u s syste m in c lu d in g th e eyes. tive afferent defetL. She had a subreLinal lesion wiLh intense
P a th o g e n e s is o f tu b e rc u lo u s in fe c tio n e v o lv e s t h r o u g h five full-lhickness ret ini Lis rn lh e tenler and adjacent small relinal
hemorrhages. Fluorescein angiogram showed gradual hyper-
stages f o l l o w in g i m p l a n t a t i o n o f i n h a l e d m y c o b a c t e r i a i n a
I luoresconce ana leakage o f dye from Ihe choroidal lesion
re s p ira to ry b r o n c h io le o r a lv e o lu s .
(H and 11. The lesLon fejmained nonfluorescenL on IC G angio­
* S ta g e I:: T h e a l v e o l a r m a c r o p h a g e p h a g o c y t o s e s t h e b a c ­ graphy i| and K.i. Kesoilulion of [ВДдГпЙаЕоЬ and flat aLro-
phic scar seen following 1real men L with anli ГIS medications.
te ria a n d e ith e r d e s tro y s t h e m o r th e b a c te ria g r o w a n d
d e s tro y Lhe m a c r o p h a g e . I f . i j u r t r a y : [ J r V i i h . i i U l^ U i a n d D r A m u d C u p l . i

* S ta g e 2: C irc u la tin g m o n o c yte s are re c ru ite d to th is

n id u s a n d p h a g o c y 'to s e th e b a c te ria . Jh e b a c te ria p re­
v e n t th e fu s io n o f th e ly s o s o m e l o th e p h a g o s o m e , th u s u v e i t i s ( s e e ]: i g u r e 1 0 . 1 5 , D ) . - S o m e t i m e s a h y p o p y o n m ay
p re v e n tin g th e ir d e s tru c tio n . be seen and th e iris n o d u le s m ay becom e v a s c u la rize d .
* S ta g e 3: A d e la y e d ty p e h y p e rs e n s itiv ity re a c tio n d e v e l­ Ls s e n tia l iris a t r o p h y has a ls o b e e n r e p o rte d , 'itib e r c u la r
o p s d e s tr o y in g th e b a c te ria , re s u ltin g in c a s e o u s n e c ro ­ a n te rio r u ve itis m a y a ls o present as a m ild o r m o d e ra te
s is . T h i s Ee s io n c o n ta in s c e n tra l c a s e a tio n su rro u n ded r e c u rre n t ir id o c y c litis ; g r a n u l o m a s a re a b s e n t in th e s e e yes
by a c tiv a te d and n o n a c tiv a te d m a crophages, T ly m ­ b u t s m a ll t r a n s lu c e n t n o d u l e s m a y b e S e e n at t h e p u p i l l a r y
p h o c y te s ., a n d o t h e r i m m u n e c e lls. If t h e c e ll- m e d ia t e d m a r g i n ( K o e p p e n o d u l e s ) . L E j j : ',' Jj1,
im m u n ity is g o o d , th e h ig h ly a c tiv a te d m acrophages
d e s tro y th e b a c te ria , th u s h a ltin g th e p ro g re s s io n o f th e intermediate Uveitis
l e s i o n a t th is s u b c lin ic a l sta ge.
P a tie n ts present w ith lo w -g ra d e s m o ld e rin g c h ro n ic u v e ­
* S t a g e 4 : E f t h e c e l I - m e d i a t e d i m m u n i t y is p o o r , t h e b a c ­
i t is - v itritis , s n o w b a ll o p a c itie s , snow lin k in g , p e rip h ­
te ria e sc a p e f r o m th e e d g e o f th e c a s e a tio n a n d m u lti­
eral v a s c u la r sh e a th in g , and p e rip h e ra l re tin o c h o ro id a l
p ly w ith in m acroph ages, c a u s in g m are c a s e a tio n and
g ra n u lo m a s . M u o re s c e in g o n io a n g io g ra p h y show s e a rly
g ro w th o f th e tu b e rc le . A fe w b a c le rta -la d e n m a cro ­
h y p e rflu o re s c e n c e o f s m a ll, d is c re te , w h itis h le s io n s in
phages m a y e n te r th e ly m p h a tic s o r b lo o d ve sse ls a n d
(h e c ilia ry b o d y band n e a r t h e iris r o o t . C y s t o i d m a c u la r
re a c h o th e r p a rts o f th e lu n g a n d o t h e r o rg a n s in c lu d in g
e d e m a is o f t e n p r e s e n t . 113
th e eye.
* S ta g e 5: ih e c e n tra l caseous m a te ria l liq u e fie s and
re le n tle s s m u l t i p lic a t io n o f t h e b a c te r ia e n s u e s i n sp ite
Retinochoroiditis Caused by
o f g o o d c e ll-m e d ia te d im m u n ity . Ilte b a c te ria e ro d e th e Mycobacterium Tuberculosis in
b r o n c h i a l v a i l a n d s p r e a d t o o t h e r o r g a n s . ■ '' [m mu nosuppressed Patients
'Jh e eye in th e im m u n o c o m p e te n t in d iv id u a l w ilh p u l­

Ocular Tuberculosis m onary tu b e rc u lo s is is in fre q u e n tly a ffe c te d . l^ a Lie n ts

w ith m ilia r y tu b e rc u lo s is m a y d e v e lo p m u ltifo c a l c h o r o i­
Anterior Uveitis d a l g r a n u l o m a s a n d , le s s o f t e n , e n d o p h t h a l m i t i s . [ 3a t i e n i s
A c u te a n d c h ro n ic g r a n u lo m a to u s u ve itis w ith m u t t o n fa t w ith A [l> S a n d tu b e rc u lo s is , h o w e ve r, m a y d e v e lo p severe
k e ra tic p r e c i p i t a t e s r iris a n d a n g le n o d u le s , and a n te rio r m u ltifo c a l re tin o c h o ro id itis , caused by M. tvte rc u Jlitifr as
c h a m b e r g r a n u l o m a s a r t 1: f e a t u r e s o f t u b e r c u l o u s a n t e r i o r w e l l a s b y t h e o r d i n a r i l y le s s p a t h o g e n i c M . Ljjj r2j j n . j!
Posterior Uveitis and Panuveitis ((М 3 S e rp ig in o u s -lik e tu b e rc u lo s is .

C horoidal Tubercles A l o K: DecFine in left eye vision to 20/40 over ft weeks in

Lhis 25-year-old Indian man. There w ere mull ilocal and ton-
M u ltifo c a l s m a ll c h o ro id a l tu b e rc le s is ih e com m on­
iluenl cream y l-esions w ilh evidence o f c.cn1ml healing in
est m a n ife s ta tio n , b e in g e ith e r u n ila te ra l o r b ila te ra l a n d HtHne Cjl them iA - C . Argjograrri showed ЬгуроПиотксепсЕ1
sa rc o id -lik e , su g g e s tin g h e m a to g e n o u s spread o f th e of' 1lie cream y edges and patchy transmission hyperfLuoies-
o r g a n i s m . 1- ' Ih e y vary fro m o n e -fo u rth lo one d is c cence o f Lhe center lEJ^F). A montage of lh e lesions showed
area in s ize , h a v e a g r a y is h - y e llo w c o l o r a n d v e r y o c c a s io n ­ bolh serpiginous and mu lifocul lesions iCi .ind Hi. His
a lly m a y h a v e a d ja c e n t re tin a E h e m o r r h a g e s ( F ig u r e Ю .1 2 , MarrtbUlc LesL was positive with 24 X 2 (Jm rt of fnduraLion,
chesL X- ray showed hilar adenopathy. T rep o n em a p a ifid u m
A -D }. T h is p re s e n ta tio n is a l s o a fe a tu re o f m i l i a r y rt B .
ha em agglutination (T PH A i tesl wan neijiilive. He received
O n c e t r e a t m e n t is i n s t i t u t e d , t h e y e l l o w - g r a y l e s i o n s t u r n
four-dru^ antii-TIJ Lherapv for 4 monlliH. f a lb h e d b>v two-
w h ite r w ith sh a rp borders a n d e v e n tu a lly get p ig m e n te d
drug Iherapy (or 1 year, along w ith oral steroids a I 1.5m ^kg
[Figure 10.12, L:).Ji:i-l[S М & Ф л & ф per day I ha I was tapered over b mdritbs; Vision £fnproved lo
20/20 at 3 months with a decrease in Eesion activity (E and J :■
Subretina I A bscess bind to 20/20 at 24 monlhs w ilh c o m p ile clearing IК .

ih e caseous m a te ria l can liq u e fy s e c o n d a ry lo ra p id m u l­ i C w i i u y } [J r V iiM i : 1 i..;> l , .u > :J I J r A r r i i w r ( j f l b

tip lic a tio n o f th e b a c illi, r e s i l i n g in n e c ro sis a n d abscess

fo rm a tio n . L 'b e s e m a y b e s e e n i n d i s s e m i n a t e d I H o r i n i s o ­
la tio n w it h o u t e vid e n c e o f T f t in o t h e r p a rls o f th e b o d y .
A h ig h in d e x. of s u s p ic io n and p re v a le n c e in e n d e m ic
c o u n trie s s h o u ld a le rL Lhe p h y s ic ia n lo th e d ia g n o s is .
C h o rio re tin a l a n a s to m o s is o r s u b re lin a l n e o v a s c u la riza tio n
m u ltifo c a l c h o ro id itis Lhai progresses lo b e c o m e c o n flu e n t
ca n o c c u r o v e r h e a l m g le sio n s [F ig u r e Ю .1 2 , t i - k ] .
a n d h a s se ve ra l a d v a n c i n g a c tiv e e d g e s (I'ig u r e i 0 . 1 3 . A - F ) ;
(2 } an in itia l p la q u e -1 ik e le s io n w tLh a m e b o id a l spread
Choroidal Tuberculom a (i'ig u r e i0 . 13, G and H ); and (3 ) in a c tiv e h e a le d scars
ih is is a s o lita ry m ass th a t is y e llo w -w h ile , e le va te d , th a t s h o w new a c tiv ity at th e ir e d g e s a n d p ro g re s s ( l l g u r e
so m e lijn e s w ith o v e r ly in g re Lin a l fo ld s and re tin a l h e m - 1 0 . 1 3 , I - K ) . W h e n a n y о f t h e s e s e i p i g i n o u s c h o r o i d i t is- li k e
o r r h a g e . 3^ 12 - - ' - " ' 1^ ” 2- ^ 5 i h e m ass can b e lo c a te d a n y ­ p re s e n ta tio n s c o n tin u e lo p rc jg re s s d e s p i t e oral ste ro id s
w h e r e i n t h e f u n d u s a n d c o n tin u e s l o g r o w b o t h in h e ig h t a n d o th e r im m u n o s u p p re s s iv e s , o n e s h o u ld suspect tu b e r­
a n d d ilT u s e s p re a d . c u la r c h o ro id itis . W orkup s h o u ld in c lu d e M a n to u x s k in
test, c h e s t X - r a y a n d С Г s c a n , a n d Q u a n t i h H R O N - T H C io l d
Serpiginous-Like Choroiditis ( Q E T - G ) t o e s t a b l i s h t h e d i a g n o s i s o f I'B . I n t h e e v e n t t h a t
i h e h a l l m a r k o f t h i s p r e s e n t a t i o n is t h e r e l e n t l e s s p r o g r e s ­ a ll o f t h e s e a r e n e g a t i v e , l3C l i o f a q u e o u s o r v i t r e o u s f l u i d

s io n o f t h e a c tiv e e d g e , w i t h th e in itia l le s io n b e in g : ( 1 ) s h o u l d b e p e r f o r m e d l o e s t a b l i s h t h e d i a g n o s i s . |Е^ Й ]

Tubercular Retinal Vasculitis ! (]. i 4 T u b e r c u l a r v a s c u Ei t i s .

A c tiv e e x u d a tio n aroun d th e v e in s and s o m e tim e s a rter­ A ki W : Vi-sron d cd in e d r^pidty I о couni finders д1 3 t|№ t№
ies., a s s o c i a t e d w i t h r e i t n a l h e m o r r h a g e s , l i p i d l e a k a g e . a n d in I h is 1 6 -усдг-uJd ш Я й w h o h,iri w id ely distributed nerve
o c c a s io n a lly w ith fo c a l c h o rio re tin itis , s h o u ld a le rt o n e fiber intaruls, rcrt i n I ЬюпкнгЬд^еы, purivunou н exudation,
to th e d ia g n o s is o f tu b e r c u la r Ш ш 1 № (Fig u re Ю . 1 4 ) . 111
and mrld vilrilit lA-El. Fluorescein angiogram showed b lo ti-
t'rom the retinal hemonha^tii, and staining and leakage
T h is s h o u ld be d iffe re n tia te d fro m s a r c o id v a s c u litis a n d
from the venous endothelium ■;H—11. H it Mantoux lesl Was
Beh^eTs d ise a se , w h ic h are m ore a rte ria l th a n ve n u ia r.
W ith tim e , re tin a l n o n p e rfu s io n H ind n e o v a s c u la riza lio n
o f th e re tin a m ay o c c u r. W h e t h e r t h e v a s c u litis Is I n f e c ­
tive per se or rep re se n ts a h y p e rs e n s itivity response to
j V I lubeTcufosH a n t i g e n s r e m a i n s s p e c u l a t i v e . ' I h e s e p a t i e n t s m o n ito re d c lo s e ly fo r p e rsis te n c e or p ro g re s s io n o f th e

s h o u ld a ls o undergo v a rio u s d ia g n o s tic Le&ls t o c o n firm le s io n s , in w h i c h case in v a s iv e te s tin g w i t h a fin e n e e d le

Т В a n d ru le o u t s a rc o id a n d tie h ^ e t's d is e a s e . T h e y r e q u i r e b io p s y s h o u ld be p e rfo rm e d to d e m o n s tra te presen ce

a n ti-Ч Б th e ra p y a n d m o n ito r in g fo r fu tu re n e o v a s c u la riza ­ o f th e o rg a n is m . A ll p a tie n ts w ith o c u la r Т В s h o u ld be

tio n th a t w a rra n ts la s e r a b l a t i o n o f th e is c h e m ic re tin a . s ta rte d o n f o u r d r u g s f o r th e firs t 2 m o n l h s a n d c o n t i n u e d

H y p e r s e n s i t i v i t y r e a c t i o n t o Т В a n t i g e n s is l i k e l y i n a s u b ­ on tw o d ru g s fo r a to ta l o f IS m o n t h s . 113,113 B o t h 9- and
g r o u p o f p a L ie n ts w i t h t a l e s ' d ise a se [s e e C h a p t e r 6 ) . T2 -m o n th tre a tm e n ts are In a d e q u a te a n d th e le sio n s are

A li p a Lie n ts su spe cted o f o c u la r ТВ/ s h o u ld u ndergo ilk e ly to re c u r a fte r c o m p l e t io n o f tre a tm e n t. Ih e h a c llti

M a n to u x te s tin g , chest X -ra y, chest С Г if needed, and d iv id e very s lo w ly In s o lid organs, u n lik e in th e lu n g ,

E Ju a n tiH iR O N -Ill C o ld test i n i t i a l l y . 113' 1;№-1,17 P C ft o f h e n c e th e n e e d f o r th e lo n g e r d u r a tio n o f tre a tm e n t. O r a l

tis s u e flu id can h e lp e s ta b lis h th e d ia g n o s is when th e s te ro id s at л d o s e o f О .э - l m g / k g are a ls o sta rte d a lo n g

o th e r te sts are in c o n c lu s ive . P a tie n ts begun on c o rtic o ­ w ith Ih e a n li-T li re g im e n , and tap e re d s lo w ly ove r 9 - 1 2
s te ro id s a lo n e w h e n a ll t h e s e t e s ts a r e n e g a t i v e s h o u l d b e m o n t h s d e p e n d in g o n th e re sp o n se .
 A p a ra d o x ic a l re a c tio n s im ila r in m e c h a n is m to Ja ris c h - 1 0 .1 4 C o n tin u e d

i L e r th e im e r m a y b e s e e n a fte r in it ia tio n o f a n t i - I E t h e r a p y
p o s itive лпс! I m m u r e d 2 0 X 2 0 m m , cb reL X -ra y sh o w Efd
th a t re q u ir e s a n in c re a s e in i h e d o s t o f s te ro id s f o r a f e w p le u ra ! e ffu s io n , V t J R L w a s г к т ге^к: Live, л r>c1 T F H A ttisL w f is
w e e k s u n til th e le s io n s b e g in to in v o lu te . rfe g a d v e . H e w a s tre a le d w ith fo Lir-d iiig i l l t i - T B Lh e m p y Hint]
N e a rly 2 b it!io n p e o p le are in fe c te d w i t h ,VJ. tuberculo­ Ih e lesions l>cj$an lo reso lve, w ilh n d e c re a se in reLinal h e m ­
sis w o r l d w i d e , t h o u g h o n ly 10% d e v e lo p a d iv e d is e a s e orrhages a n d u d u r n « f a n d shea Ihi ng o f I h e v iin S a) 3 m o n th s
in th e ir Eife tim e . IV v e n Ly -lw o c o u n trie s have been id e n ­ iL -L " : a n d () m oflltte ':Q a n d lij. A n g io g ra m s b o w u d p a tc h y
nonfEuoTesccm ce a n d va s c u la r г а т п е й й к й i S - L !:. H u d e v e l­
tifie d th a t harbor 80% of th e w o r ld 's ТВ p o p u la tio n :
o p e d n e o va scula ri za.\io n el Ih e re tin a r c ^ u iiir j ’ s e ttle r laser
In d ia , C h in a , In d o n e s ia . B a n g la d e s h , P a k is ta n , N ig e ria ,
p h o to c o a g u la E io n in the u p p e r te m p o ra l q u a d ra n L in ilia Ily (5J
th e rh iJip p in e s , S o u th A fric a , (h e R u s s ia n fe d e ra tio n , a n d in ft'To n asa ] qLLadraril subset]lj-ln-Liy fT , V , a nti W ..
K -th io p ia , V i e t n a m , th e D e m o c r a t ic R e p u b lic o f (h e C o n g o ,
iCuurtesy: D r Vnhadi С4цз1а and Dr Amcsd CrijpLn.l
B ra zil, T a n za n ia . K e n y a , 'lh a ila n d , M y a n n ia r} A fg h a n is ta n ,
U g a n d a , P e r u , Z i m b a b w e , a n d C a m b o d i a . 1'1" 1
W hen it occu rs f o c a l Iу in th e c h o ro id , it p rodu ces a d d i t i o n t o j V I. Ы о т с и к ы ? , m a y c a u s e т и I Li l o c a l c h o r o i d i ­

a n o n s p e c ific c h o ro id a l in fla m m a to ry m ass s im ila r to tis a s w e l l as r e t i n i t i s i n p a t i e n t s w i t h A t t > S . - J :

Lb at s e e n in c ry p to c o c c o s is , n o c a rd io s is , o r o t h e r i n f l a m ­
m a to ry d ise a se s the c h o r o i d i n c l u d i n g s a r c o i d o s i s
o f tales' Disease
( f i g u r e 1 0 . 1 5 , A - С ) . A lar^e c h o r o i d a l t u b e r c u l o m a m a s s A s m a ll s u b g r o u p o f L a le s ' d ise a se p a tie n ts who present
m a y s i m u l a t e a m e l a n o m a a n d m a y f a i l t o respoEid t o a n t i - w ith recurrent vitre o u s h em orrhages, p e rip h e ra l venous
T B t h e r a p y ." 1" B a r o n d e s e t a l. d e s c r i b e d a h e a l t h y p a t i e n t s h e a th in g , and re tin a l n e o v a s c u la riza tio n m ay have a
w ith a n e g a tive tu b e rc u lin s k in te st a n d a fo c a l c h o ro i­ h y p e rs e n s itivity re sp o n se to tu b e rc u lo u s a n tig e n (se e
dal le s io n w b ic b on trans pars p la n a b io p s y c o n ta in e d C h a p te r 6 ].
a c i d - f a s t b a c i l l i . 1"'0 , 1 < i n s o m e a p p a r e n tly h e a lth y p a tie n ts P h ly c te n u la r c o n ju n c tiv itis is an a lle rg ic response to
Lbe d ise a se m ay progress ra p id ly to p ro d u c e a p ic tu re of v a rio u s m ic r o b ia l p ro te in s in c lu d in g Lu b e rc u lo u s p ro te in
p a n o p h th a lm itis . iw h im -in lr a c e H u la r e , in (Figure 10Л5, E),
LEPRO SY EH. £5 Tubercular choroidal granuloma.

A Iо lhrs 2fc-year-oJd HtV-negiilivG Indian man com ­

Leprosy is a c h ro n ic g ra n u lo m a to u s d ise a se caused by p la in ^ } о I a progressive decrease in vision over 3 miifflffiaj
j ^ j r a f c a c C e n u j n ie p ra fy D e p e n d i n g o n th e i m m u n o l o g i c sta- He had a recenl loss o f weight anti respiratory illness. I— J is-
Lus o f i h e p a tie n L l h e d is e a s e p r e s e n ts in th re e f o r m s : le p - visual acu ily was c.ounl finsert on the rijjhH and 2tV20 on lhe
ro m a to u s w ith p o o r c e ll-m e d ia te d im m u n ity . tu b e rc u lo id [efL side. A large tuberculoma occupied Ihe entire m acula (A1
w i t h g o o d c e llu la r i m m u n i t y a n d b o r d e r lin e [tu b e r c u lo id
w ilh smaller lubencleH in ihe mid periphery. A fine needle
aspiration biopsy was positive Гог M y c o b a c te riu m tu b e rcu lo ­
or le p ro m a to u s ). l3o l a r le p ro m a to u s le p ro s y is t h e aner­
sis by KCK. He received fouT-druj’ anli-TB Iherapy; 2 wcieks
gic f o r m o f th e d is e a s e w it h m a r k e d l a r k o f cel I - m e d i a t e d
Irilcj s - i и| resolution be^an iВ :. The lesions looked much
im m u n ity . I'h e s e p a t i e n t s h a v e a h i g h b a d e ria l i n d e x ; t h e
EessaUive al 2 months (C).
b a c illi g r o w a n d m u L lip lv w ith in Г о л т у m acrophages a n d I): Lar^e mullein fill keraliu precipitates suj>gesLirtg jiianu-
are t r a n s p o r t e d t o a ll p a r t s o f t h e b o d y , lh e b a c te ria are lumalous uveilis in ibis 17-year-old Indian плап recenlly
known n o t to to le ra te w a r m te m p e ra tu re s a n d are f o u n d mi^raled La Lhe Ln ile d StnLfis from India. In ad d ilion, he bad
in th e c o o le r p a rts o f th e b o d y - s k in , p e rip h e ra l nerves,
severe vitritis. His chest X-ray was negative but ManLoux Was
positive with a necrolit read ion at 24 X- 2(?mm. H e received
cornea a n d iris i n t h e e y e . I L e n c e t h e r e a r e n o f i r m l y d o c ­
four-drug antii-ГВ medical ion and topical steroids lor I S
u m e n te d cases o f le p ro s y a ffe c tin g th e re tin a and cho­
mqifltfls-, w ilh rosolulion of all sryns and visual recover у (о
r o id .1 " Л case w i t h fu n d u s in v o lv e m e n t in th e fo rm of 20/20.
h e a p e d -u p , h ig h ly re fle c tive , w h ite m a te ria l re p o rte d in E: rhlyt'lenuldr oonjunclivitis, ал immune response seen ir>
th e lite ra tu re by Choyce and a n o lh e r fu n d u s le g io n by paLienls w ilh tuljerculosis.
C h a t t e r [ e e i n 1 9 6 4 1 11 h a v e n e v e r b e e n fu rth e r s u b s La n li-
Leprosy,
a te d , t h o u g h a c o u p le o f e n u c le a te d eyes h a v e s h o w n th e
F: Madarosis,. peripheral corneal scarring Hi^ns Ы uveitis,
p r e s e n c e o f Л-J. le p ra e w i t h i n m a c r o p h a g e s i n t h e r e t i n a a n d
and loss o f nasal cartilage in ibis Indian palienl. w ilh lepro-
c h o r o i d , ' [ ' h i s is v e r y u n u s u a l a n d e x t r e m e l y r a r e . 1 1 maLous ieprosv.
O c u la r in v o lv e m e n t is m o s tly lim ite d to m a d a ro s is ,
ifJuLirr-L-.y: А - - Г , [ 3Г J. Ш-Л\.!Л; I: .llld к 1 >Г i . R . h^!. j I ll I . IГ11
Ea c k o f c o r n e a l s e n s a tio n ., b e a d e d c o r n e a l n e r v e s , k e r a titis ,
g ra n u lo m a to u s a n te rio r u ve itis w ith iris a tro p tiy . fc e ra tic
p re c ip ita te s, le p ra p e a rls in th e iris, a n d in v o lv e m e n t o f
th e s k in , la c r im a l sa c, a n d lid m u s c le s r e s u ltin g in l a g o p b -
tb a lm o s (I'ig u r e 1 0 .IE ? , F). C la u c o m a occurs secondary F U N G A L R E T IN O C H O R O ID IT IS
to iris c h a n g e s a n d u ve itis . E .o w in tra o c u la r pressure has
a ls o b e e n f o u n d d u e t o in filtra tio n o f (h e c ilia ry b o d y and C e r ta in fu n g i e ith e r in v o lv e p r im a r ily th e re tin a o r e x te n d
d e c r e a s e d a q u e o u s p r o d u c t i o n . 1 ' " 15 ra p id ly fro m th e c h o r o id in to th e re tin a w h e r e t h e y p r o ­
H is t o lo g y o f e n u c le a te d b lin d eyes h as fo u n d b a c te ria d u c e w h ite u ltra re tin a ! f u n g a l a b s c e s s e s [ A s ^ f & O u ? Jitm i-
and fo a m y m a c ro p h a g e s la d e n w ilh M iepnft in th e cor­ ga i [j’i , C a n d id a a lb ic a n s , rlh c h o s p o w n b eigeliir S a d o s p o r iu m
n e a , iris, a n t e r i o r u v e a l tis s u e r a n d a n t e r i o r c h o r o i d d u e Lo i r p f c s p F r .'f l n?pz, and Sp&vthtix j c j i f u c f c r j '} . O th e rs produce
its a f f i n i t y l o c o o l e r a r e a s , lh e re tin a w a s fo u n d t o b e fre e p rim a rily y e llo w -w h ite m u ltifo c a l c h o ro id a l in filtra te s
o f t h e b a c i l E L 15 ^ th a t m ay cause serous and h e m o rrh a g ic re tin a l d e ta c h ­
J'h is a c i d -fa s t b a c i l l u s c a n n o t b e g r o w n in v i t r o a n d h a s m ent (H is & ^ ta s n vj H ^ tvrrk ifrtLJi^
o n ly been c u ltu re d in th e fo o t p a d s o f th e n in e -b a n d e d C o c c id io id e s i m r n f l i j , a n d C typ to c p ttx ts n e t fc m t U n s ] . T h e s e
a rm a d ilEo . decent use o f reverse tra n s c rip ta s e -p o ly m e ra s e la tte r d ise a se s m ay be a s s o c ia te d w ilh d is c ifo rm re ti­
c h a in re a c tio n . ( H T - P C H ) h a s e n a b l e d c o n f i r m a t i o n o f th e nal d e ta c h m e n t. M u c o rm y c o s is in va d e s b lo o d ve sse ls
d ia g n o s is in several c a s e s . ' ''' ' i h e d is e a s e is e n d e m i c in and pre se n ts w i t h v a s c u la r o b s tr u c tio n s u c h as c e n t r a l o r
In d ia , N e p a l, B ra ziEr a n d th e tro p ic s o f A s ia and A fric a , b ra n c h re tin a l a rte ry o r o p h t h a l m i c a rte ry o b s tru c tio n , d u e
w i t h 709o o f a ffe c te d in d iv id u a ls re s id in g here. t o t h e r a t h e r l a r g e s i ^ e o f t h e h y p h a e . I 1* * - 163
 E f J . \ ft
C A N D ID A R E T IN O C H O R O ID III S C a n d id a s e p tic c h o rio re tin itis .

Л: Focal Carilffida retinal abscess w ilh 'u(]lIon Lull vitreoLte

] lo s p ita lix e d p a tie n fe , p a rtic u la rly th o s e w it h p o sto p e ra ­ opacities in Eh is 23-year-old wom an w ith a history of EV rlrujj,
tive c o m p lic a tio n s o f a b d o m in a l su rgery re c e iv in g p ro­ use. She was diagnosed initially w ilh toxoplasmosis unlii the
lo n g e d in te n s iv e a n tib io tic tre a tm e n t by an in tra v e n o u s his-lory of drufj use was unearthed w hile she was Lryiп^ lo
c a th e te r are p r o n e to d e v e lo p c a n d id e m ia a n d Focal w h it e Ljtiy druj^s on the hospital campus from a ^ibHoT'. She under-
re tin a ] abscesses (3: i g u r e Ю .1 6 , The fo c a l
wen I a viLrat'Lomy, and lun^al stains and cultures wore posi­
tive tor C a n d id a albicans.
w h ite re tin a ! E e s io n s are t y p i c a l l y s u p e r f i c i a l l y l o c a l e d in
.nui ( : I Ii ■ ■
11j| j.!il ii'i 11'ц1
. ii- lm ( ,i.r;(Vil.i',i ■
: I:■:чч-:jnc i. :i i:i-.
th e re tin a and are fre q u e n tly a s s o c ia te d w ilh s m a ll c o t­
Note ihe predominantly j}rantilomalous inflammation o f the
to n y b a lls in th e vitre o u s o ve rlyin g th e p rim a ry le s io n
retina and vilreoretinal juncture. The ov^yyinE vilreous con­
( E 'ig u r e 1 0 .1 &, D } . O t h e r p r e d is p o s in g fa c to rs f o r d e v e l o p ­ tains predom inancy fiitLrocryLe.1^. Special slains revealed evi­
m e n t o f re tin a l c a n d id ia s is in c lu d e [V d r u g a b u s e , c h e m o ­ dence ot" M o n ik a \arrow , В I. hJolh yeasi and hyphae are sej^j
th e ra p y c o rtic o s te ro id a d m in is tra tio n m a lig n a n t bone in the overlying vi1rc4^us of a patienl w ilh Candida relinitis -iCj.
D I о G : C a n d id a endophlh-almitis in a 5 О-уеаг-old rrt'an w ith
m a r r o w t r a n s p la n t a t io n , d ia b e te s , severe b u r n s , e n d o c r in e
(.hnonic alcoholism who noted pain Lind redness in his ri^hl
h y p o fu n c tio n - o th e r d e b ilita tin g d ise a se s, c o n ta m in a te d
eye. Visual acuity was 20/50. Note tEie string o f w hite vibt-
in tra v e n o u s ly a d m in is te re d m e d ic a tio n s , and m a te rn a l
ous opacities (D and Eij. C a nd id a albican.1- was cullured from
b irth c a n a l W e c d o n . 16 3- ^ 1^ 11^ 1 ™ - 1 ^ Ih e a u th o r has the Vitreous and from ah ulcor on the boltom of hiя fooL IF-:.
s e e n t w o d i a b e t i c p a t i e n t s d e v e l o p i n g C a n d id a r e t i n i t i s f o l ­ At the lime ot v iIrecLomy, intravitreal am photericin E3 was
lo w in g u re te ra l s te n t p la c e m e n t w h o s e u rin e c u ltu re g re w ^iven and syslemic admi nisi ral ion of tanoconazole was
C a n d id a jjJfrtcjiru_ Eie^ n . Six weeks laler Visual acuily was 2СУ23 and ih e fun­
J ' h e a p p e a r a n c e o f t h e f u n d u s l e s i o n is s t r o n g l y s u g g e s ­ dus was normal (G).

tive o f th e d ia g n o s is . Ih e d ia g n o s is m a y b e c o n firm e d by A s p e rg illu s c h o rio re tin itis .

c u ltu re s o f th e s ite o f IV a d m in is tra tio n , b lo o d c u ltu r e s ,- Hi lo I: This 1 3 -year-old man, w ilh a hisLory of ' b r u i s e d Tibi
o r v itr e o u s a s p ir a tio n . M u l t i p l e w h i t e -c e n te re d s u p e rfic ia l and chills', 3V drujj abuse; a n d a 1- d a y history ot e y e pain
r e t i n a ] h e m o r r h a g e s m a y a l s o o c c u r . l!i'L I h e w h i l e c e n te rs and visuaE fuss in the rr^fit eye, had a visual acuity o f 2/200
m a y b e c a u s e d b y m i c r o a b s c e s s e s c o n t a i n i n g t h e f u n g i , 37 6 in the rifthl eye and 20/20 in the left eye, mild iritis, v iIri­
tis. and a suEjhyaloid -lo p .wruw. Hi and subnet ina I hypopyon
or by s te rile fib rin -p la te le t a g g re g ate s (se e p r e v i o u s d i s ­
tJ>oEion? arrow , Hi associated w ilh a subretinaJ hemorrhagic
c u s s io n o f p y o g e n ic b a c te ria l in fe c tio n ) , f'h e d is e a s e m a y
inflammatory mass in ihe ri.^h-1 macLila. (lu llLines ot Lhe aque­
respond to syste m ic a lly a d m in is te r e d a m p h o te ric in Б or ous humor and blood, echocatdio^aphy. and H3V serology
5 -flu o ro c y Lo s in e , or b o t h .' ' 1 1 ' " In tra v itre a l in fe c ­ were negative. An intravitreal injection of amphoLericin B,
tio n o f a m p h o te ric in E5 h a s been used su c c e s s fu lly as a 5 ;(j", wab done. Vitreous £ j I L u r e was posilive C(h Aspvrftiifus
p rim a ry fo r m o f t r e a t m e n t L,' , , J I ’" l ' l>'1' a n d as a n a d j u n c t t o flavui'. He received IV amphotericin В for Э weeks. Eleven
sy s te m ic tr e a tm e n t ( R g u r e 1 0 . 1 6 , C - H J . 1 ' 1' M o r e re c e n tly , mofflhs later tiiH visLial atLiilv was 20^400 and Lh ere was a

f l a t s c a r in t h e r r ^ h t m a c u l a (].'■
flu c o n a zo le , vo ric o n a zo le , and c a s p o fu n g in have been
s u c c e s s fu l in tre a tin g СитиЩ а re tin itis in a d d itio n to . o r H i s t o p l a s m o s is r e t in o c h o r o id itis ,
w ith no re sp o n se to , S p o n ta n e o u s j 1o L : Thin 2^-yeaf-old-man with ALUS died Eiecauso ot ttm -
r e s o l u t i o n o f Qa rttfrrfdi r e t i n a l a b s c e s s e s m a y o c c u r . ir'o г pJicalion^ ahsotiatod w ilh ‘■vlom e^ilovirus pneumonitis antJ
th is reason p a tie n ts w ith m ild re tin a l in v o lv e m e n t and syslemic histoplasmosis. He com plained of a hazy spot in his
left eye. H e had multiple w lule foci of retinitis in l>oth eyes
n o e vid e n c e o f o th e r o rg a n in v o lv e m e n t m a y b e fo llo w e d
(I). V licio sco p ic exam ination ol hts eyes revealed multFlocal
fo r e vid e n c e o f p r o g r e s s i o n . Ih e d e v e lo p m e n t o f re ti­
artias of n e tro liiin ^ perivascular retiniliH iK. and choroiditis
n a l s t r i a e a r o u n d a f o c a l r e t i n a l r n o n i l i a l a b s c e s s is a s i g n associated w ilh И . capvulatum organisms iarrow, L..
s u g g e s tin g e a rly r e s o l u t i o n o f t h e l e s i o n . ' ' 4l I f t h e r e t i n a l
li, MUftci-y Dr K,tTL;n^ Н.'.ч; L... njurlt'bv Chll^lph I.llj.Il': I ! Ггг^ш h: l ■
: lit
Le s io n (s ) progresses, o r if e v id e n c e o f m o r e a d va n c e d d is ­ vi a J.^ J
e a s e is p r e s e n t , t h e a d m i n i s t r a t i o n o f J l u c o n a z o l e . i t r a c o n ­
a zo le , v o r ic o n a z o le , p o s a c o n a z o le , o r c a s p o fu n g in m a y be
e ffe c tive . T o a v o i d renal to x ic ity a s s o c ia te d w i t h tre a tm e u L abusers a n d o fte n can b e m is ta k e n f o r T o x o p la s m a r e t i n i ­
w ith s yste m ic a m p h o te r ic in Ei, s o m e p a t i e n t s w i t h o c u l a r tis. I V e s e n c e o f a ' s t r i n g o f p e a r l s ' a n d a b s e n c e o f K y r i e l e i s ''
in vo lv e m e n t in th e absence o f e vid e n c e o f o th e r organ a r t e r i o I i t is a n d o l d s c a r s a d j a c e n t t o a c t i v e r e t i n i t i s s h o u l d
in vo lv e m e n t w ith m o n ilia l in fe c tio n m ay be m anaged r a i s e t h e s u s p i c i o n o f C a n d id a ; e f f o r t s s h o u l d b e m a d e Lo
s u c c e s s fu lly w ith pars p la n a vitre c to m v and in tra v itre a l c o n fir m a h is to r y o f IV d r u g a b u s e s in c e th e tr e a tm e n t fo r
i n ject i o n o f a m p h o Le rici n ] J . 1 1 ?y- 17 9 j : H* r l й t h e t w o c o n d i t i o n s is i t a s t l y d i f f e r e n t .
C a n d id a r e t i n i t i s is m o r e c o m m o n i n p a t i e n t s p o s t g a s ­ 'I'h e d e v e l o p m e n t o f e p i r e t i n a l m e m b r a ties m a y b e t h e
tro in te s tin a l s u ig e ry, h y p e r a lim e n ta tio n , to x ic m e g a c o lo n , cause o f v is u a l loss in som e p a tie n ts o th e rw is e success-
and in d ia b e tic s , w h e re a s in fe c tio n s are m ore I'u lly tr e a te d f o r c h o r i o r e t i n a l m o n i l i a l in f e c t i o n . -S urg ical
c o m m o n ly seen post organ tra n s p la n t or c a rd ia c su r­ r e m o v a l o f th e s e m e m b r a n e s m a y re s u lt I n p a r t ia l r e s to r a ­
g e r y . E n a n o u t p a t i e n t s e t t i n g , C a n d id a is s e e n in EV d r u g tio n o f v is u a l fu n c tio n .
ASPERGILLUS RETINITIS
l i ^ i ^ n ( ] | | drug abuse is lhe Ш т а г у cause o f intra­
ocular infection with AsfwF^iJ/iJj. in these palients it ranks
only behind Candida as the cause o f endogenous fungus
endophthalmitis, ll is also acquired in an oigan irans-
pJant immunosuppnessed stale, vftlereas Gfrbfrd# *1 see» (Д
patients лfler gastrointestinal surgery1 and hyperalimenta­
tion.1'" 1 4 OcnEar involvement is typically the first mani­
festation o f the infection except when it occurs in immune
incompetent individuals.Id2--'J '['he patients present
with suhacuLe visual loss, mild pain, and redness of (he
eye that may be associated with a varying degree of ante­
rior chamber reaction. Chorioretinitis and endophthalmi­
tis caused by Asp&giUw have characteristic clinical features.
L>eep retinal or choriorelinitis with progressive horizontal
enlargement of the lesion is characteristic o f Asp-ergiflHJ as
compared to Candida that has a smalt retinal focus and
grows progressively into the vitreous/5 5 , Preretinal or
sub retinal exudation may be accompanied by a hypo­
pyon as a result o f layering of inflammatory cells (figure
10. ifi. С nind H ].jaQ A hemorrhagic retinal vasculitis may
he present.1'' 1 Isolated retinal hemorrhages and prereti­
naE fluffy vitreous opacities may obscure fundus details.
In some cases only a mild VEtrilis may be present initially.
A variety o f species o f AspeygiHus may be responsible for
human infection. Pars plana vitrectomy and systemic
azoles such as fluconazole, voriconazole, and posacon-
azole are the first choice in treatment c t Aspergillus infec­
tion of the inner eye. intravitreal injection o f voriconazole
cact be used as an adjunct to systemic therapy.
Uao and HidayaL found Aspf^iT/Mi to grow preferen­
tially in the sub-KPbi and subretinaL space and to invade
choroidal and retinal blood vessets, whereas Crwrifdir grew
preferentially into the vitreous cavity in eyes enucleated for
fungal endophthalmitis.1" ' 14,1
Retinochoroiditis Caused by Other Fungi
Other fungal diseases* such as trichosporonosisJ,ul and
spo rot richos is,14‘' J l'2-J 1'S№dinspa)ri&r?r tipiospenj^inn,211" 21 й
and 'J ' may cause chorioretinal lesions and
endophthalmitis similar to that produced by ЕаШйЛз,
COCCID Ю IDOMYCOSIS
Primary infection with the fungus Coccidtojife imniUis,
[ike Lhat with f - / t$piv]a£umr is a common cause
o f an acute, benign, self-limiting pulmonary disease: H
is most prevalent in the interior valley's o f California. It
is unknown whether it is a common cause o f subclinical
chorioretinal scars and Sate visual complications similar
to those found in areas where histoplasmosis is endemic
(E-'igure SO. L&, A -C )."' '* As part o f the primary infection,
this fungus does occasionally cause loss o f vision second­
ary' to focal infectious granulomatous choroiditis, retinitis,
and endophthalmitis (figures 1 0.17 , A - С and ]; Ю . IS , D
and E ).J” , J J -_J1lj Patients inhale the anthrospores causing
[ fj. E7 C o c c id io id o m y c o s is .
A lo F: This 4 2 -year-old wom an noEed a paracentral bfur in
her rij^hl eye w.Eiile Jiospilalized for coin muni eating hydro­
cephalus. ih e w jh previously diagnosed and I пел ted with
fluconazole ior aMicidioidom yL os is. pneumonia and m enin­
gitis in California. Her visual acuity was ЙО/1'5 in both eyes.
She had an old choroidal star lemporal lo lhe m acula and a
newer Lesion inferior to fixation in bef right eye 1A). The let-
Egw eye had a laint lesion in the posterior pole and several in
Lhe mid periphery ; \i and Ci. Angiogram showed staining, of
lhe legions ■LJ and Ej. ^he undenvenl a vcinlriculoperitoneal
shunt and reced ed systemic anlifunyals; Lhe paracentral sco-
Lama improved over b weeks.
С Lo I S : Л з Ъ -like illness developed 1 month л tier а I rip lo
Arizona in I his 43-year-old man which resolved in 2 weeks.
Three monlhs laler he experienced proarifessrVply worsen­
ing Jow back pain, which on M R i sl>owcd я rinpi-enhanciпщ
abscess in the disc between L2 and L3 (G). A biopsy of Lhe
^bscess revealed ch remit grarfulomaloiis i/tfjarnrriatkjri w ill:
thick-walled spherules conLainrny endotpores (C M S slain' IH
and Ij. Pour monlhs later he noted metamorpbopsia in Lhe
left eye and a decline in vision lo 2CVft0. I Ь н е were no signs
of inf lam million. Let! tujidus showed cream y chortfidal
lesions Hj>. one o f w hich showed intense leakage consistent
with a choroidal neovascular membrane IК and L). An O C T
showed heaped-up cells anterior Lo (Eie pigment epithe-
IiLim i.Vli. Hiii visual acuilv impfoved Lo 20/50 after inLraviL-
real inj eel ions of bevac i zum ah and Lhe lesion improved on
O C T (K!).
IQ lurtrcy: A -К U r liu.L L i- N , U r i V L i t h n w V I . ' K ' i i i v h i : ^nrl
U r SiK.hin iV.ud'.-.jrj, A , L-, I |W N, AJ:cj. Y ;in n u j^ i. L .iw T t itt ; I . Ihu
hltlin.iJ ЛИ .is, b a d ijd r n 2 < т1 ^ 7 В- а- 7 С 1 ?П - П 1 П - Я p . i b ]
pneumonia, which secondarily may spread via the blood­
stream, most often to the CNS and bones. I'tu-like symp­
toms, cough, erythema nodosum, and arthralgias are often
the presenting symptoms. J [ydrocephalus and meningitis
have been reported (Mgure 10.17, A-F}.
CRYPTOCOCCOSIS
Cryptococcosis is a chronic or subacute pulmonary sys­
temic or mentEigitic infection caused by Cryptococcus nco-
formnm. ""' "'lf- ' ' 1 Salients with (he meningltic form o f the
disease may d e v e lo p papilledema, papillitis, opLic atrophy,
and eKlraocular muscle palsies (E:igure 10.TS, С -I) Spread
lo the justapapiElary choroid and retina may occur directly
or via [he bloodstream. Multifocal irregular yellow-white
choroidal lesions, focal subretinal masses, and vilreoreti-
nal abscesses have t>een described, usually in debilitated or
immunosuppressed patients {figure 10. IS. I-') .-A['''
24,6Sijnultaneous diorioietinal infection with Cryptocwcus
and cytomegalovirus has occurred^33,241 Cryptococcal cho­
rioretinitis may occasionally occur in apparently healthy
patients prior to their developing evidence of meningi­
tis.''' ' When coil fined lo the choroid and outer retina,
the lesion may simulate a variety of diseases, inc3uding a
melanoma, focal granuloma, or a disciform exudative pro­
cess { figuLe W.]&, F u ц jnnporlant lo
consider the possibility o f cryptococcosis before placing
a patient cm corticosteroid treattnoltr which may cause
,1 llu n n a ijt .iiilI !.:.L,lI >prc.id ni' \':w i iilav.-.m.'''' Mu'
diagnosis may be confirmed by examination o f (he C5E-'
and vitreous. Treatment with the newer azote anLifungal
agents will cause resolution o f the infeclion/v , , i 4 J ’ ~,''l'i
ipontaneons resolulion of Intraocular lesions occasionally
occur*.
PHYCOMYCOSIS
(MUCORMYCOSIS)________________
'] hough rare, mucormycosis is a severe, often fatal fungal
infection unless diagnosed early, caused by fungi o f ihe
Zygomycetes class. ]is classic presenlation is in an immu­
nocompromised hostr often With severe diabetes and keto­
acidosis, cancers, cirrhosis, or renal failure, and in patients
on immunosuppressives and steroids. H ie route o f entry is
mostly through inbillation of fungal spores, Lhough per­
cutaneous entry can occur. Ocular involvement is usually
due to contiguous spread from rhinocerebral mucormy­
cosis, and patients present with ophthalmoplegia, rapid
decrease tn vision due to central retinal artery or ophthal­
mic artery occlusion, multiple large nerve fiber infarcts,
and bypolony .-'"-1 l6]'-4 й - Intravenous entry can result
in endogenous endophthalmitis (Kigure 10.19, A —IJ .” ' 1
253 Early diagnosis ts by clinical examination o f the oral
and nasal cavit# and confi rmalton by obtaining scrap-
Eng£ or biopsy from the dark eschar in these areas, '['he
hypbae, which are lar^e, nonseplale. and highly invasive,
spread rapidly into soft tissue and blood vessels (iigure
10.19, В and C). They exert their effect by occluding ocu­
lar and orhiral 'l i ; v , i; | \ and tlx- vasa nervorum, resulting
in proptosis, phthalmoplegia. and choroidal ind retinal
infarcts. Treatment consists o f early extensive debridement,
local and IV amphotericin, and newer atilifungals such as
p osaco n azole.J s ■■1™
I fl . E3 C o c c id io id o m y c o s is , c r y p lo c o c c o s is r a n d
b lasto m yco sis^
Л to ( . : Presumed ocular coccidioidom ycosis in a 4l6-yeaS
old man w h o lived most of Ын I Lit? in southern California
bird A rliim a , Ho bad д diagnosis of' pujfljiitmaiy coc-rtdicridct-
myctK-is ль a young man. H e was visually a$yrtj(ptdfnatit unli!
recently, w t r ^ he noted drslorted vision in the lefl eye. l-Ee
had bilaLeial imjllifoi.nl chori ordinal and j Lrxl^p^ipi11лту ScbfS
Identical to that seen in presumed ocular histopEasmosis syn­
drome iJ’O H 5). A lype Lt subrelinal neovasculai membrane
and subtovea] blood were pnesenl in the left eye.
D and E:: Focal f^anuloma observed clin ica lly in the fundus
oE" a 28-year-oEd man w h o died ol disseminated co ccid ioid o ­
mycosis. High-power view shows multiple spherule-conLain-
injj; H^dospOTts (аггоИк Lj.
F: Ei^cal c h r>ri rsru-l i nit is c-au-sed tjty C ry p ta c O c c U i n ecfe rm a tis
in a nonimmunosuppnessed 41-year-old man with obstruc­
tive hydrocephaEus. Tbeie w ere no vitreous cells. "The eye
became blind Iram endophthalmitis. Diagnostic enucleation
established Lbe diagnosis.
С and h : Severe bilaLeral papilledema caused by
^ ry p io c o c c u s meningitis with optic neive rnvolvemenI in
a iti-yea r-old non i гпгп и nosuppressed woman with i e v e e
headaches and fever of unknown etiology. SEte died and histo-
palholo^ic examination revealed encapsulated Cryp toe occur
organisms I'ajTLtw!' in the optic nerve (H) and brain.
I:. E let. Iron micrograph of encapsulated C r y p t e c o c c u s organ­
isms in Ihe choroid.
I to K: Multi local blastomycosis choroiditis in a 43-year-
old man w h o developed lever, chills, cough, anti blurted
vision soon after a hunting Uip. He had mu hi focal lesions
In the lun^. skin, and choroid bilaterally (J and Kr. H e failed
to respond to anti-ТВ medication. BFopsy of skin neveated
biaslomycosis. The ocular and svslemic disease responded
promptly to amphotericin E3 therapy.
ID and t Irum Uoychin jrrd f-Ir o m Shields---14; I Ггит AvEndjnir^1^;
I arid I i-Hjrilii.l'iL-d Wilh pcim is-s-:i in Irum [hh1Amhdrlt.bn Iriurn.Ll liI
(J;»!i4i.il'ikili.i^v; cr^л r^’l'il bf ttitOp3ilkulrt»lc MliLiIIiIi пД Сй..: I iimI V.
cfiLtrttiy JJt j-ruii'Lic A. Ci'.ilm.m.j
 » 'ь.
77^
V и
f v
■ .

J V * - > ■*
* ■ y — - * t
- V
V * ■■
‘ V V : . - ■ ; ' « ^ ’ .
i 'л Й _ - * * г л - ■ ^ <
j* - i> ■ * v j . Л '

J t, ,- .’ ^ ^
4^ ' . 1*

* -■ h ^ ' ? ; fct у
. 4 > * ' • * * * 1 ^
BLASTOMYCOSIS
Endogenous infection with BJtTstomycw follow­
ing inhalation o f conid ia into the lungs may cause multi­
focal choroiditis (l-'igure 30.13r J and K}, endophthalmitis,
and panophthalmitis.-' ' Whereas pulmonary and cuta­
neous granulomas are the mo&t frequent manifestations
o f systemic blastomycosis, ocular involvement occasion­
ally occurs and may affed otherwise apparently healthy
patients.^5,2-*'1, Biopsy of skin lesions, if present, is helpful
in establishing the diagnosis. The ocular as well as Lhe sys­
temic infection may respond favorably to kelocona^ole,
amphotericin, and newer aaole therapy.
HISTOPLASMOSIS RETINITIS
AND CHOROIDITIS IN IMMUNE
INCOMPETENT PATIENTS__________
ujpjjjfjturrf may cause multifocal, active,
white- retinal- subretinal, and choroidal lesions in one
or both eyes o f patients with AiL>b (figure 10.16, |-L)
от other immune incompetent stales [see Eigure 3.43..
A -C )J]27r3:iit-157r3sa In immune incompetent individuals
histoplasmosis may cause focal choroiditis thal typically
results in multiple focal atrophic chorioretinal scars xvith-
out producing ocular symptoms. These scars later in life
may be the site o f development o f subretinal neovascular­
ization and visual loss (see presumed ocular histoplasmo­
sis syndrome in ChapLer 3).
']'hough rare, mucormycosis is a severe, often fatal fun­
gal infection unless diagnosed early, caused by fungi o f the
Zygomycetes class. ]ts classic presentation is in an i m mu no­
compromised host, often with severe diabetes and keto­
acidosis, cancers, cirrhosis, or renal failure, and in patients
on immunosuppressives and steFoids. lhe route of entry
is mostly through inhalation o f fungal spores, though
Из. E9 Mucormycosis.
A t e I: A man in Endia with 50-day history of sud­
den onset decrease in vision, 5 Hays after receiving IV fluids
during a h ydm cd e rofiiir. hi it vision was 20 /2 0 in Lhe гсцЫеуе
and Louril flttgers [n the left u ™ . 'fhr? righ-l цуи was рйртти!. The
IF!-ft vitreous was еОЙ&нпет ha/y ,i.nd no fundus detail? were
seen (Aj. H e underwent a pars plana vitrectomy For a diagno­
sis or endofle&aLA endophthiilmilib ,md received iripavitrtel
va псотпус in, ampholpji с in, ceftazidime, iind destine th arsons.
CytfllcrtV revealed muoor with broad liyphae branching at
ri^jht ап-gles (B iind C , arrowl. An ear, nose, and lJifoal evalu­
ation for sinus disease was negative. H e was Created with oral
itraconazole, Lopic-a] stuio-ids, and jsnlibiolius. Fohtopora lively
inulliplo foci о I rcrtan i<is- and periarterial plaques iL>r E, and 14.
were noted that scarred t*w f 1 month* 11).
l ( j j p j : r i g h l J г if l
M u l i . i B .V . 2Ш Н , -
j . hГ.ч jit i. j Г QphlhaSnio/agy, S tie lm : ^ Нимпень
O f A r n a d G u f t k , C i - u | i l ; i t\ ^ < m . I k > v K , k . ; i u i J r u l . t l .
b m J n ^ i i r u u r . i n v l c I j l r j i n l . ^ n h l l - . i l m i l i ! - i n ,ь п i i n n l u n o L u m i w t L ' n l p a t i c r t f .
IгHOphlh.ilrriLri. ^MJ4:2Dr4l:.^l.i-R. l\iuit 2(X3Blun 5.1
percutaneous entry can occur Ocular involvement is usu­
ally due to contiguous spread from rhtnocerebral mucor­
mycosis, and patients present with ophthalmoplegia, rapid
decrease in vision due Lo central retinal artery or ophthal­
mic artery occlusion, multiple large nerve fiber infarcts,
and hypot o n y , i n t r a v e n o u s entry can result in
endogenous endophthalmitis (figure 10.13, A -I).' "
harly diagnosis is by clinical examination of the oral
and nasal cavity and confirmation by obtaining scrapings
or biopsy from the dark eschar in these ntreas. lhe hyp hue.
which are Large, non septate, and highly invasive, spread
rapidly into st)ft tissue and blood vessels (Kigure 10.13, ft.
C) they слеп their effect by occluding ocular and orbital
Vessels and the vasa ne:rvomm, resulting in proplosis, oph­
thalmoplegia. and choroidal and retinal infarcts.
Treatment consists of early extensive debridement,
local and IV amphotericin, and neuter antifungals such as
posacona/ole."'
T O X O P L A S M O S IS R E T IN IT IS 10.20 Co ngeni la I loxoplas mosis re tin it is.

A to D : HeteiolopLa of tilt1 m acula and dragging of (he reLi-

lo xo p la s m o s is is t h e m o s t f r e q u e n t c a u s e o f f o c a l necro­ nal vessels erf ihe rijjhl t*ye (A and B'i caused by congenital
tizin g re tin itis in o th e rw is e h e a lth y hum an in d iv id u a ls toxop lasmos.it relinilis in л 29-ytaarald mmur> w ilh inLra-
[E 'ig u r e s T te p ro to zo a n Tinccrplasma craniaE calcification .=iл d focal cErorEoretinal scars and С !■
.
is e i t h e r t r a n s m i t t e d t o t h e f e t u s i n u t e r o w h e n th e Note angiographic of r-olinochoioidal anastomosis
m o t h e r a c q u ire s ih e in fe c tio n d u rin g pregnancy or le ss fit Iho si1t! of the star in the left oye i.arrr;av.. p ).
E and F: M acu la r scars in an HlV-posilive infant presumed
c o m m o n l y r EL i n f e d s i h e r e t i n a M < W n g in ge st t o n o f ih e
to be caused by congenital toxoplasmosis.. Visual acuity was
o r g a n i s m , ' [ ' h e r e is a p r e d i l e c t i o n ( o r i n f e c t i o n o f ( h e C ] N ! >
2Q/20r right eyer and 2 0 /4 0 , [eft eye.
and th e re tin a . In c o n g e n ila E to xo p la s m o s is th e re tin a l
G It) I: Presumed oongenilal toxoplasmosis in a 32-vear-old
Ee s io n m a y o c c u r as p a r t o f a g e n e r a l i z e d s e v e re in f e c t io n wom an with poor vision since hi n i l . Note the deep D-Kcava-
(e n c e p h a lo m y e litis , c o n v u ls io n s , fe ve r, ja u n d ic e , cere­ tion cjf ihe star in lEre righl т л е й la.
bral c a lc ific a tio n , h y d ro c e p h a lu s , and p a ra ly s e s o f va ri­ I and K: M ultiple choriofetmaE scan o f uncertain cause in
o u s typ e s J o r m o r e fr e q u e n tly as p a r t b f a m ild s u b c iin ic a l
bollt eyus o f Lhis 9-year-old th ild w ho had good vision unlil
recently w hEn she developed evidence of suliiolinal n«*vas-
in fe c tio n . Large, a tro p h ic , o fte n e xc a vate d , c h o rio re tin a l
L‘j l a riiatiori in the left ma^Uia. Stic was the producl of an
scars c e n te r e d in or near ih e m a c u la r area o r e ls e w h e re
Я-month piejjnancy that was leTminaled Eiecause of rotardud
in ih e f u n d u s in c h ild r e n a n d a d u lts are p r o b a b l y c a u s e d in1:a ltI eri i»e growth.
in m a n y cases b y c o n g e n it a l t o x o p l a s m o s i s (I'ig u r e 1 0 .2 0 ,
B, C r H, \} a n d K ). W hen th e y are s y m m e t r i c how ever
th e s e m a c u la r le s io n s m u s t b e d iffe r e n tia te d fr o n t s im ila r-
a p p e a rin g in h e r ite d d y s tr o p h ic le sio n s .
 Whether acquired in ulero or postnatally the Ikwplasmn 10^21 S e ro u s m acti Far d e la c h m e n I c a u se d b y
organisms may Eie dormant in (he encysted form in the a c tiv e o u te r re tin a l t o x o p la s m o s is a n d b y s u b r e lin a l
apparently norm aI retina, either adjacent to or remote n e o v a s c u la r iz a tio n a risin g at a to x o p la s m o s is

from chorioretinal scars. When the organisms become c h o r io r e t in a l scar.

unencysted, one or more acute, whiter necrotizing lesions A to E: This 13-year-old wom an developed floalers associ-
т а у occur in a previously normal-looking retina or at the nlud w ilh a I d c a area of acuLe norm i Ii н urroav, A I and w id e ­
margin c f an old chorioretinal scar (Mgure ! 0.2 !j. "Ihe spread periphlebitis in the right eye. Angiography showed
lesions usually involve the full thickness оГ the retina but intense staining in lhe area of I hit1 rriin-itis and leakage of dye
from the major retinal veins and opJic disc -U and O . ie v e ia l
in some cases may be confined to either the inner or less
yean. later, she developed visual loss caused by serous reti­
frequently, the outer h a l f of the retina. ]n the former they
nal detachment in the m acula associated w ilh multiple foci
are associated with oVeriyhig vitreous in fb irmiatory cell of outer rhinitis near Lhe edge o f the old scar and in Lhe
in filtration. When the retinitis involves primarily the outer papillom atular bundle area (arrows, D)_ Angiography (b:-
retina, serous detach men L o f the underlying retina ts fre­ revealed early staining c l the foci ol retinitis and lale diffuse
quently presen L [Figure 10.21 r А -I). When Lhe acute lesion slain in ^ o f the subrelinal fluid.
includes a major retinal vessel, it may cause either a branch F 1u 1: ierujLis macular detachment caused by recurrence of
retinitis. i.j глл'г1
? , J- л rid (Li/ near л scar. Note lute staining of
retinal arterial occlusion (Rgure S0.22 , A-CZJ-3'--' JlL7'? 0 o ra
the suhrcilinal ftuid.
venous occlusion (figure 30.22, D and E jj '"
J and K: Serous macular, dutachmient caused bv recurrence
Most patients with acute relitiitis are seen initially o f reLfnitis i,arrow, I r i n a patient w ilh bilateral m acular scars.
because o f a history of floaters and less often because of L: ienoscingu i nous retinal delacbm enl caused by subrelinal
loss o f central vision caused by foveal involvement by neovascularization arising at lhe inferior edge of a loxoplas-
focal retinitis {ligure 10 .2 ]}, cystoid macular edema., inosis scar.
or detachment associated with paracentral focal reLini-
Lis. Focal periarterial exudates and arterial atheromatous
plaques (Kyrieleis' arLeriolitis) simulating arterial emboli
maty occur either in the immediate vicinity of the acute ret­
initis or remote from it [Figure 10 .22 , p-l].*6,7"™ -275'3*2-293
Huorescetn angiography shows no permeability alterations
or evidence of artery obstruction in the area o f the arte­
rial plaques but demonstrates marked fluorescein stain­
ing in the area of the retinitis [E'iguies 10.21, В- C, 1:. I I,
and E; 10.22, Cj. T.he periarterial plaques may fade or may
persist following resolution o f the retinitis. Occasionally
acute multifocal arterial wall opacification is widespread
throughout the fundus and may be accompanied by simi­
lar multifocal gelatinous-appearing opacities scattered
along lhe major retinal wins. Ophthalmoscopic and angi­
ographic evidence o f diffuse perivenous exudation may
occasionally occur in areas remote from the acute reLini-
Us. The presence in those patients with retinal vasculitis
o f reduced levels o f antibody affinity to retinal 5-antigen
with normal levels of circulating immune complexes sug­
gests a defective regulation of antiretinal auto imm unity.
Swelling o f the optic disc and angiographic evidence o f
staining o f the disc may accompany focal areas of retini-
Lis or, in some cases, may be the presenting manifestation
o f toxoplasmosis (Figure 10.22.. f-L). Multiple, small, gray
deposits [presumably inflammatory cells) may develop
along the inner retinal surface in the vicinity of the acute
retinitis, and it may be difficult to distinguish these from
small foci of active retinitis. If the vitreous separates from
the retina near the acute lesion, these gray deposits usually
remain attached to the posterior surface of (he vitreous.
 The active focus of retinitis usually e n larges far a period
o f 1 - 2 weeks before gradually fading over a period of sev­
eral months, usually leaving in its wake a pigmented atro­
phic chorioretinal scar. Segmental optic disc pallor may
develop in the zone of nerve fiber alrophy caused hy the
retinitis.
In some patients the onset of the disease is charac­
terized by Lhe development o f multifocal small foci
o f retinitis, largely confined to the outer retinal layers
(Figure Ю.23. After resolution, some of these
small lesions may leave no chorioretinal scarring, '['here
may be a series of remissions and exacerbations before
development o f the larger, more typical ful [-thickness
focus of acute retinitis (E'igurc 10.23, A-D). Another atypi­
cal presentation is that o f an acute papillitis before the
development o f a focal area of retinitis (Figure Ш.22 ,
l-L),-*6^ 7^ 93' ^ Findings that suggest that disc swell­
ing may be caused hy toxoplasmosis are severe vitreous
inflammation- fluffy while peripapillary lesions, nerve
fiber h Lin die defect, and often good visual acuity.
The clinical diagnosis of ocular toxoplastnosis is always
a presumptive one. Most patients wrill demonstrate skin
test and serologic evidence of previous contact with ihe
organism wilh positive IgG lite r s .^ 'I’he diagnosis of acute
toxoplasmosis is very likely in otherwise healthy patients
with a focus o f acute retinitis in an eye wilh one or more
chorioretinal scars. Eiven m Lhe absence of anoLher scar, a
solitary focus o f acute retinitis in a healthy patient occurs
most often in patienLs with serologic evidence of the infec­
tion with positive IgM antibodies; a few do nolr and the
liters may be low in many patients, [n addition to the
enzyme-1 inked immunosorbent assay (bLiSA) Lesl, the
immunofluorescenl antibody test, and the Sabin-l'eldman
dye Lest (rarely done anymore), detection o f evidence
o f toxoplasmosis in lhe aqueous hutnor may be accom­
plished using PCR."'....... . Cytologic diagnosis of toxoplas­
mosis may occasionally be made from vitreous biopsy.4"
Most chorioretinal scars caused by toxoplasmosis are
atrophic, partly pigmented, and associated writh postin-
flammalory changes in the overlying vitreous and a
nerve fiber bundle visual field defect. I lypertrophic dis­
ciform scars, however, develop En some patients (figure
10.23, b and F). In rare cases reactive proliferation o f the
R PE in these scars may be mistaken for a melanoma.
Remodeling of lhe retinal circulation caused by previous
occlusion of vessels passing through the area o f redrntis is
often presenL (Figure 10.22, D and bj. Evidence of retino-
choroidat anastomosis may develop due to full-thickness
retinal iEivolvemcnl and subsequent atrophy, thus bringing
the retinal vessels in close proximity lo the choroidal ves­
sels (Figure 10.22, D}.-' ™ Development o f sub retina!
neovascularization, usually type 2 , at the edge o f an inac­
tive scar may cause loss of central vision (Figure 10.21,
Jis.ioj i ar^e macuEar chorioretinal scars seen in
Ш .2 2 T o x o p la sm o sis re tin itis .
A to C: Branch retinal arLeriaE occlusion caused by -acute
nelinilis, presumed lo be Loxoplasmosis LA>. Angiography
showed evid en ce 01 branch arfpra o b slrjclio n la ftp w , B) Hind
Nile plaining in I be атеа of rc.4i n iris (C .
I ) and E: KeLintJchoToidal anastomosis Id^row.1;! in Lwo
patients lollow ing venous obstruction caused by toxoplas­
mosis reLiniliH.
F Lo I: ChoritHelinal scars !Hl and marked periarteriaJ p3aque
depusilioi: persisling Гиг years tollu^'jng Tnultiple areas of
acute Telinilii presumed to be caused by loxoplasmosis in a
30-year-ckld man w hose visual acuity was 2 D/20 in both eyes.
Angiography showed evidence of the periarterial plaques and
minimal evidence of obsLruclion Lo Ljlood flow Ц).
] Lo L: Presumed hiSDplastnosis papillitis in a 7-yeai-old Lioy
wiLh acLile loss of via ion in lhe ri I eye J) . Angiography
revealed sLaining of the optic disc {K>. W ith in several months
the disc sw elling resolved and optic atrophy was evidenl.
lw enty-one months laLer he had furlhej Зоьы of vision in- Lhe
ri^fil eye caused by acule reEinitis in the m acula (LK
children and atLrEbuted Lo eongeintal toxoplasmosis usu­
ally do not show evidence o f postinftammaLory changes in
lhe vitreous. Unusual and unexplained associations with
toxoplasmosis re Li nit is are the development o f Fuchs' bet-
erochromic cyclttis and either un El aLera! or bilateral zones
of retinitis pigmentosa-like fundus changes." ’’ ,u5‘ 507 Gary
Holland has categorized (he location aflbxoplasma ret in i-
lis into three zones: zone 1 [3000 microns from the fovea
center or 1500 microns from the optic disc margin), zone
2 (from zone 1 lo the anterior borders o f the vortex veins),
and zone 3 [from the anterior border of zone 2 to the ora
serrata).
Familial involvement with ocular toxoplasmosis is rare.
In southern Brazil (Alto Uruguat region}, however, famil­
ial ocular toxoplasmosis is endemic.1M|'-,u 'l he prevalence
of ocular toxoplasLnosis there is 30 limes higher than else­
w h e r e ^ with S 5 % o f the population being infecLed and
18% o f them have evidence o f retinochoroidi-
Its. lhe frequent ingestion O f raw or undercooked pork
has been suggested as a possible explanation for this. In
the United Slates, the prevalence o f 'F garnfri infection is
22.5%, although lhe prevalence o f ocular involvement in
ihese is only 1 % .
'Lbis difference in the prevalecice rales in different parts
of the world is likely related to Lhe prevalence of the dif­
ferent genolypes. Lhree genotypes have been isolated
in humans and animals: types E, Ji. and LJI. 'Fype ]] is the
mildest genotype and is seen in the Uni Led States and
Hu rope South America, especially southern Brazil, has
the more virulenL type E and aLypical genolypes. Sexual
recombinants (atypical genotypes) also have increased
virulence.m
L J
 Even though toxoplasmosis is considered да endemic
disease, there have been a few outbreaks around the
world3'1-31* and a recent epidemic in Coimbatore, a city in
southern India.ll0/5i' ilS Ihese outbreaks and clustering o f
cases have been linked to a source - either contaminated
municipal water or infected kittens and a feral cal harbor­
ing the more virulent genotype. The largest epidemic has
been reported from one center in southern India where
248 palients (254 eyes) with relinochoroiditis were seen
between August 2004 and July 2005. O f the 230 eyes
(30.5% ) with unifocal retinitis, 67% were located in гопе
I, 25% in zone 2 . and the remainder in ione 3.
Although recurrence iб a hallmark of Tttwpfdijmd reti-
nochoroiditis, no definite facto r(s) has been found to
trigger recurrences. The risk of recurrence decreases as the
disease-free intervaE increases; however once a reactiva­
tion occurs, the risk of further recurrences increases (clus­
ters). Ihis is likely from some of the oocysts degenerating
over time and hence the smaller load o f dormant cysts.,
hut with a recurrence the number of organisms increases,
thus increasing the chance of another recurrence. I]atieiits
greater than 40 years o f age had a higher chance o f recur­
rence,- Likely from altered immunologic slate. The longer
Lhe duration of infection, the greater the chance o f recur­
rence,- again implying organism load. " "
I iistopathologic examination of an acute toxoplasmo­
sis lesion in eyes of immunocompetent patients reveals a
focal necrotizing retinitis associated with an underlying
acute and chronic granulomatous choroiditis and scleritis
(E'igures 10.23. G and H; 10.24, Л and B }.'j4;'!'he inflam­
matory reaction surrounding the necrotizing retinitis is
markedly reduced in immunosuppressed patients [figure
10.23, [). In spite o f the presence o f scleritis LhaL may be
evident uhrasonographicallv beneath the focat retini­
tis in immunocompetent patients, oniv occasionally do
they complain o f pain .*'1 lhe encysted and free forms of
Тторкы ш organisms are found in the relatively normal
retina surrounding the necrotic retina (I'igure 10.23. J and
IQviBD.jsi xhey are occasionally found in the choroid in
imm unnsuppressed patients.
The value o f pyrimethamine (Daraprim), suliadiaz-iite,
clindamycin, minocycline, trimethoprim-sulfamelhoKa-
zole, and corticosteroids in the treatment of active lesions
in immunocompetent humans is uncertain.
Treatment probably has no value in preventing recur­
rences.1^ Ihese drug£ have been demonstrated to be
effective in experimental infections with Tbxopjaimto in
animals. I here is only minimal evidence, however that
they are o f value in the treatment o f toxoplasmosis in
LfJ.23 Toxoplasmosis retinitis.
Л to D: M ultifocal .suhacиLt1 rut rudcfscun: гоГiniIiн presumed
La bo caused by toxoplasmosis in a 17-year-old yirl w h o was
seen initially wiLh a l-monlh hitlory of blurred vision ii: Lhe
right eye (A). Visual acuity was 20Л 00 in the right eye and
J 11 j n .1 :1ч Iн■11 i'v i1 1ii:-i i." wfiH1 no vilreous cells. Note Lhe
multiple, small, gray Easterns in Lhe I'oveolar area (ajroivsE.
AnjftagjrapEry aL 11i L lime showed ntt evidence of ЕЕиотеь-
cein staining. Photographs taken at 2- lo 3-month intervals
over Lhe subset]uenl several years showed n frequent change
in the position of the jjray lesions and no evidence initially
of residual R f t changes ■L-5i. llu: visual acuity remained
unchanged. Seven years л Her her in ilia I ejistfrifti^rticm, she
relum ed with acute loss ot vision in Lhte right eye. There was
a large атеа oF acule rrfimtis in lhe righL macula (C;. O ver
Lhe subsequenL (> years, ^he had oLher acute aLLacks. W h en
lhe pntienl was lasL seenr visual acuity was 20/200 and a
Lar^e alrophic m acular scar was presenl (Of.
£ and F: A t Live toxoplasmosis retinilis :tl resolved and pro­
duced an elevaLed hypertrophic scar wiLh retinochoroidal
anasLomosis IF:-.
G : Acube lox^plasmtjeis retinochoroiditis in an im m uno­
competent patient. Ncile lh e п есн и ic retina separated by
ЕЗшсН'и membrane i.amuavi from л focal a ran el" ihicktMimg of
lhe thoroid by granulomatous Irtflimmatioirr.
H: Focal area of granulomatous choroiditis and scleritis
underlying toxoplasmosis retinitis Fn an immunocompelenl
adult.
1 to K: F’holomicrographs ot acute focal necrotizing
Taxaptaim a retinochoroidilis in an Fmmunosuppresied
paLienL. Nole Lhe lass o f nuclei in all layers wiLh patchy pres­
erve! ion ol" a few pholonecepLor n ud e! iind nongranuloma­
tous inflammatory reaction in Lfie underlying cftoroid (I!'. A
high-power v ie w of lhe lesion shems encysted organisms
and free lat hyzoires (K, arrow'..
ciour'.ii-iv' l? r A n d n .i v P. I-L'rry. rjr^M inlL'L'l ni!. V iirh ic w ff i-NL n :lv . I
H Ir o m h k K ^ u i ,m iJ / i m i i K . ' i m j n ■ I К c liu t Il^ v [ J r H , i ! p h L-.i^jl<
immunocompetent humans.-'1'' Most authors agree that
treatment is unnecessary and inadvisable in lesions out­
side the macular area. In cases where the center o f the
macula is threatened- use o f one or more of the antibiotics
in combi nation with systemic corticosteroids is advisable.
Intravitreal clindamycin at a dose of 1 mg is a rapid means
of treating retinitis, and can he used in fovea-
threatening cases, in severely immunosuppressed patients
for a quick onset, and in pregnant women .3J4,110 ]'opical
corticosteroids and mydriatics are indicated in the pres­
ence o f accompanying iridocyclitis. Lhose children born
to mothers who acquired Tbxoplasrna during pregnancy
should be on агШ -Жгор^!™ treatment up to their first
birthday.
 In patients With AIDS or who art iEnmunocompre­
m in d for other reasons, toxoplasmosis may cause л
fulminant and widespread necrotizing retinitis as well
as eft^ephalitis.ll!1,:!^] SJUiJ1 f-'eatures of toxoplasmosis
retinitis in patients wilh A ID S that differ from those in
immunocompetent patients are multiple aclive lesions,
infrequency of acute lesions arising adjacent to Jhactrvc
scars, frequent involvement of both eyes, and frequent
evidence o f CN5 involvement. Some o f these patients
present with mu]tifocal. small, widely scattered lesions
that may rapidly become confluent and produce a clini­
cal picture identical to acute retinal necrosis.1 ^ Vitritis is
usually present but may be less than that seen in immuno­
competent patients with similar size retinal lesions.
ClinicalEyr the retinal lesions may simulate those caused
hy cytomegalic inclusion disease/1'" although typically
retina] hemorrhages are less prominent and vitritis more
evident in lesions caused by toxoplasmosis. Toxoplasmosis
encephalitis, is a leading cause o f death in patients with
A I L > S „ Approximately Ю - 2 0 % of patients wilh intracra­
nial toxoplasmosis develop retinal lesions.''' Involvement
o f the brain often occurs in the absence of ocular involve­
ment. toxoplasmosis may cause either a diffuse necrotiz­
ing encephalitis or discrete space-occupying intracranial
Eesions. In the formerr computed tomography may be
norma!; in the Ealter, it may show focat lesions with
ring-shaped enhancement after contrast infusion.331*
Coinfections o f lhe retina and choroid may occur.11 '■!M
lh e reLinal and the brain lesions caused by
respond favorably to pyrimethamine and sulfadiazine,
but recurrence o f lhe infection is common after cessation
o f treatment.1" 1 Corticosteroid treatment may be nec­
essary to reduce cerebral edema but probably is uunec­
essary in the treatment o f retinitis since the intensity of
the inflammation is less than in normal patients.,,fl the
results of serologic tests in patients With A ID S are unreli­
able: lhe presence of elevated JgM in as many as 13.%
o f these patients suggests a high incidence o f acquired
infection .^ ’1
Solitary active toxoplasmosis retinitis may be simulated
by other infections [Ctuidida, pyogenic bacteria, bacteria
o f low pathogenicity in patients with AIDS, cat-scratch
disease bacillus}r ischemic retinopathy, and neoplasia
[large-cell lymphoma. metastatic carcinoma to the retina).
Retinal artery occlusion caused by a focal area o f toxoplas­
mosis may appear similar to that occurring in patients
with acute multifocal retinitis associated with cat-scratch
disease or of unknown cause (see figure 10.04], and
patients with bilateral idiopathic recurrent branch retinal
arteiy occlusion (see figures (S. 10 and 6. 1 1 ). Multifocal
1G.24 T o x o p la s m a g o n d i i re tin o c h o r o id itis .
А [о C: N ecrotic retina displays cysts of Toxoplasma gondii.
the 1iioroid reveals chronic: giSniilopiiatdtta inflar^rTiatkwi i.-V
hon-iiiLoxy Iin and eosim. Multiple toxoplasmic cyslt Hire pres­
ent in lhe retina and Lhe cysts show presence of bradyzoites
lU, .irsxnv, periodic, acid-ichiffi. U 11rasl met u гл Г features cjf a
retinal Toxoplasma g o n d ii cysL containing Eiradyzcii Les IQ .
M a la ria re tin o p a th y ,
D to |: A 2(J-year-old Indian man with high intermittent
fevers dia^nobcid сМ пклЛу as гпл1агы t:im p lain ed of visual
Foss in his left eye 10 days after fever unset. A patch of rc*4ini-
Lis with decreased MQplasrn^C fhm- was seen adjacent I о Lhe
disc (D k The angiogram showed nonfluorescence o f the area
with I,'il4J tLainjnj» o f lhe edges iE л п-d F). four weeks later lhe
relinal opacification had improved w ilh lipid exudales in a
slar paLtc^m. A branch conunf’ off lhe ]п1его1еплрогй1 аМиту
sfnm-ud shenlhinj> {G J. The? Eu I low-up an^iofjram shciws nar-
rowiid flow Ihrou^h [he aiffecled jrLuriole w-ith no taLesLain-
injj erf tbe affected relink IH-I).
lC 'n L ir C L - iy : A - i ' „ U r Ч ,1 Г Ч П Ц К . ю : U - . I . U r V h h . i l i L i u ^ . i . '
outer toxoplasmosis may simulate puncLate inner choroi­
ditis (pseudo-p resumed ocular histoplasmosis) (see E'igure
11.21-11.27!), and diffuse unilateral subacuie neuroretinitis
(see figures Ю.28 and 10 .2У).
MALARIA
JVdJjfrrihfrzmi итг*. R fiiloporitm, fi uwifc. P. muhintie, and
J3. hnowksi are the parasiLes causing malaria character­
ised by intermittent fevers - chills that recur on a regular
basis every 24-4&b depending on the parasite subtype,
liach year up to 3 million deaths and 5 billion episodes of
clinical illness are reported, wilh 90% o f them occurring in
Africa.
Cerebral involvement with ^Jdmrmciiujn falnpatuitt
malaria major is an important cause of mortality, particu­
larly in children in tropical regions.11* Ihose manifesting
papilledema and outer retinal edema outside the major
retinal vascular arcades are mi)re likely to die or survive
wilh neurologic sequelae. Other fundus findings include
retina] hemorrhages (orange color hemorrhages due to
the associated anemia), cotton-woo I spots, intraretinal
edema, narrowed and obstructed arteries and small capil­
laries in the macula, and venous distension and tortuosity
The erythrocytes that have engulfed the parasites are less
pliable and block sin a11 vessels causing the small retinal
infarcts and hemorrhages [Figure 30.24, A-С) The reti­
nal whitening resolves over timer as do the lipid exudates
[Figure 10.24, D - F ) ^ - 45*
PNEUMOCYSTIS IIROVECI
CHOROIDITIS
jinn/eci (pronounced "yee-row-vetsee'1', pre­
viously known as P. елггигг) is an opportunistic patho­
gen in patients with various humoral and cell-mediated
immunologic abnormalities and is the most common
infection in patients with AID S [over SG^b)."531 It ivas pre­
viously classified as a protozoa п.. but reclassified in 199S
as а yeast-like fungus based on nucleic acid and btochemi­
ca [ analysis. Its name was changed in 2ЕЮ1 Lo Аймтосугйз
jiroveti, a species specific Lo humans. 11 is a normal com­
mensal o f the pulmonary system and becomes patho­
genic in immunocompromised stales. Piim m jcysiis firw eci
infection is the initial manifestation o f АЮ 5 in over 5СЙЬ
o f patients. Those With T- and li-cell abnormalities appear
more susceptible than patients with Ei-cell d e ficie n t
alone, infection with РлиЕшогудй may be life threaten­
ing. in humans infection is primarily Limited lo lungs>
Lymph nodes, spleen. £ltd less often Liver, bone marrow,
.small and large intestine, pericardium, myocardium, hard
palate, periureteral soft Lissue, and choroid. lfncumocy5lis
jirow ci choroiditis often occurs in patienls receiving long­
term aerosolized pentamidine therapy.' 3' 3bl Clinically
the multifocal choroidal Lesions are placoid or slightly
elevated, yellow-while, round or oval, multi tabulated, and
variabiy sized, with finely granular FiPL that may si inn Late
Lesions seen in large cell lymphoma., metastatic carcinoma,
atypical mycobaclerial infection, sarcoidosis, or 15aIen-
I'uchs nodules [E-'igure I0.25, Л -hJ. The choroidal Lesions
progress slowly and are associated with minimal vitre­
ous reaction and visual Loss. Although both eyes are usu­
ally affected, unifocal unilateral lesions may occur.1 "x '
Angiographically these focal Lesions are hypofluorescent
early, and stain late fig u re 10.25, В and 1"
is a unicellular organism wiLh many mor­
phologic features but it is considered to be a fungus (figure
10.25r 31 and Et exists exclusively in extracellular
spaces. Et is not readily cu Iin red 'ihere is no reliable sero­
logic test for identification: most recently TCR for its t>N,\
is being used. Diagnosis depends upon demonstration of
organisms with special stains - methenamine silver, lolu-
idine blue, or Giemsa. Silver stains primarily the mature
cysts [Figure 30.25, ij. Choroidal infiltraLes are acelluEar
eosinophilic, vacuolated, and frothy, and involve the full­
thickness choroid including choriocapiLlaris [ligure 10.25,
G and Voz] (,r hemorrhage and cal-
cifLcalion may be present, biker stains show I iisttipliisnni-
Like organisms (I'igure Ю.25, I]. lileclron microscopy [EiM)
provides a definitive diagnosis and shows irophozoiles and
Lhick-walled cyslic organisms [ligure 10.25, J). lhe over­
lying RE’E: is usually mini malty affected.
Treatment consists o f IV or oral therapy with tri­
methoprim-sulfamethoxazole, dapsone, pentamidine, or
co-trimoxazole.-^ '14 'r,L' 4,1 l>otentiaE side effects include
1 0 .2 5 Pneumocystis jiroveci c h o r o id iiis in p a tie n ts
w ith A ID S .
A Id E" This 24-yail4ild HIY-posiLive n u n StesenLed w ilh
л 3-monlh history of Pn&ttfpacy'Stfe pneumonitis arid л
1-monLh his lory severe headaches пеЗлЕи^ to central ner­
vous system cryptococcosis. Н у had ло visual comptaints.
Visual acu ily was 1 0/20 bilaterally- The fundi of bolh Щ&Ь.
showed w id e ly scattered, mulLrtoc.al, partly t’onfluejil.
sIi.^HlIV elevated, cream-colored lesions :Al. Angiography
reiteswsd early blockade o f chartHdal tliJprescence лг^ late
slain ini| oE lhe choroidal lesions iht and (.! . The patient was
treated w ith IrimeLhoprim, sulfameChoxazoEe, am photericin
K, and fijucona^to.le IV'. О уеГ following 2 weeks he noted
progressive Гои. of vision in both eyes. Ttie choroidal lesions
were unchлni^cd but he developed early рлрчИШв <D). His
vision decTmed Lo counting finders only in both eyes. Six
weeks mIpt ihere Wiis evidence of partial resolulion of the
chonoidili.1. h.il Lhic? papillilis had inc reused (EJ.
F lo j: This 34-yoar-old man w ilh A ID S and fjufrrtonary pneu-
mocysLosis had received multiple medications including
pentamidine inhalation LreaLment. H e had no visual com-
plainls when he was discovered Lo nave inulliple сгилт-
colored choroidal lesions in both eyes (F)'_ H is visual acuity
in the right eye was 2Q/J0. He died .} weeks laEer. Cross
uxiim:nation of лп L>ye removed intim л .15-yeaT-old ptiliLml
w ilh A U J i and Htwumoi.yMi.'; рпеитоп1л revt^nfed mLilliple
yellowish placoid lesions involving the choroid Iлrraws, Gf.
Histtjpnlliolof’ic.illv lhe (.horcjidal lesions c-onsisted o:f eosin-
ofjhiEit, Hcellular, vacuolalEid lesions iH: |1пл1 when stained
with mdhenannin.E!-silvcT slain demonstrated Cystic organisms
[arrow , 11. Electron m icfoscopy ге\елк^ c vsts, some of which
c o n fin e d inlracyslic Ewdies '.arrows, Jl.
I F —I i N .im K . t u e t .iJ .
neutropeniar thrombocytopenia, skin rash, fever, nephro­
toxicity- hepalotoxicity, and others. Tarlv ophthalmoscopic
detection o f choroiditis may save sight as welt as prevent a
fatal outcome. E-'ailure o f the choroidal lesions lo respond
lo treatment should suggest the possibility o f a coexisting
infection of the choroid, e.g., Mycobacterium а\>1ит-1пиже1-
Utlarc, Стурктроащ ncofonmms, MycobacleT^tm titLwcuiesis,
and Mi'sEf^fdUfrfcj CLrftfu/tfJuHi.'' 7■41,1
Ocular as well as other sites of infection wilh
probably occur at Lhe Lime o f spread from
pneumonitis. Ihese lesions become inactivated but not
sterilized and may reaclivate at a later lime. Patients
receiving prophylactic aerosolized pentamidine iherapy
are not protected against extrapulmonaiy disease, hence
i mm lino-compromised patients are on prophylaxis with tri-
methoprim-sulfamethoxazole or co-trimoxa£ole. [’resumed
Г. jjriw rf choroLdiLis served as a marker for disseminated
infection"''' before oral prophylaxis, '["he number o f 1EEV
cases developing P |(rff[«rfi choroiditis has since dropped
dramatically. O nly two case reports have been seen in
the past decade, one an LIIV patient on a low dose o f co-
trimoxizolf! and another a post transplant leukemic
p a tie n t .^ "^ 1
TOXOCARIASIS
Fatbits, typically heahhy children or young adults, may
experience unilateral loss o f vision secondary to inva­
sion o f the eye by a single second-stage larval form o f
the lbxo£d^a L'rtnri ascarid (Figure 1D.2 & ) . : '■ lhe eggs
o f lhe dog ascarid are deposited in the soil, where they
undergo a change required before ihey become infectious
to humans, Who contract the disease primarily by inges­
tion of contamunited soil and not by direct contact Wilh
dogs, ['ol losing hatching o f Lhe eggs in Lhe gist rot n Lest inal
tract, lhe second-stage larvae invade the blood vessels of
the gastrointestinal trad and enter the eye, probably via lIil-
uvea I tract. Bilateral ocular Invasion probably occurs rarely.
Jhe patients manifest a variety of clinical pictures, Includ­
ing: [1] localized disci fori n macular detachment f E'igure
10.26, A -C );J65 [2] multifocal granulomas with intercon­
necting tracks, so-called meandering toxocariasis (figure
10.26, h-E);v" : (3) peripheral disciform retinal detach­
ment; (4) papillitis;"'" { 5 ) optic nerve head
tumor (l-'tgure Ю.26, D and peripheral
retinal or pars plana mass with vitritis (unilateral pars pla-
nitis; i'iguie 10.26, [_ ^ и .э й в л л м 75 щ retinaJ detach­
ment; (3) endbp^thalmjtls;367^ ^ 375,5^ and [У) cataract.
Ihese patients typically bave externally quiet eyes In spile
o f having endophthalmitis. 'Lhe organism, which measures
approximately .W0-400 pm in length, is at the subbio mi­
croscopic level in s iz e / '"''" ' ' ' " It presumably enters
the sub retinal space by way of the choriocapil laris, where
it may incite an eosinophilic granulomatous reaction and
cause a serous and hemorrhagic disciform detachment of
Lhe retina (Hgure A J . ^ ' ^ 'U i e reaction may destroy
the overlying retina and extend Into the vitreous [E'igure
10.26, C ).iM,3™,J75 On healing, a gray or white umbllicated
disciform scar, often with retinochoroidal vascular anasto­
mosis, may result (Tigure EG.26, В and
'lhe diagnosis of a subreLinal granuloma caused by
З&тсягд ijjffj'y is presumptive. Eiosinophilia can be demon­
strated in some patients. The ocular disease rarely occurs
tn children wilh other clinical evidence o f visceral larva
mi grans (coughing, wheezing pulmonary infiltration,
hepatomegaly, leukocytosis*, persistent eosinophil la, eleva­
tion o f isohemagglutinlns, and elevated serum im m uno­
globulin levels}. Visceral larva migrans occurs presumably
wilh ingestion o f a large number of eggs.""''
ffjJis is rarely if ever the cause o f ocular toxocariasis. 'I'he
ELISA tesl may detect serum IgC antibodies in as high
as 9 0 % o f patients with clinically suspected ocular dis­
ease 1ы к,й'м^зе9' ihe ELISA test titer o f aqueous humor
and vitreous Is usually higher than that demonstrated in
the serum and in some cases may be positive when (he
serum shows no evidence o f antibodies.1411-'10'' Ih is is
Likely due to intraocular antibody production. Monoclonal
antibodies to larval excretory-secretory antigens that bind
wilh species specificity to the cuticular surface of Infective
larvae may prow to be o f value in the laboratory diagnosis
o f Ю М м ^ а в Ь ,3’3'-^
K i . ' J Intraocular toxocariasis.
A: 5iиЬгиИiплI granuloma wilh surroundinjj subrel iпаI hemor­
rhage in a Ц-уеаг-йУ ^irl wilh presumed Тыхосага cants.
B: Organized butjielLnji |^лпи]огпл w ilh retiraKjhOrOltJ^I
^ im o m o s is in а 1{^year-old gid w ilh presumed Тй^ВслГа
c & n is .
C: Organized suEjielinal granuloma with extension of the
mass into the vitreous in ал З-уелг-oid buy with preRumtfd
Гозсос ага c jn i s .
D and t Peripapillary Jom ca ia ^in ulu m n and extidalive mac­
ular detachment in л 4-year-old girl. The eye wan enuclealed
Едагливе of the possibility of refinoblasloma. Hislopalhologic
EKflminalion revealed a peripapillary subretinai eosinophilic
I’ ranuioina surrounding а кж х'а га organism yarrtyw, t..
F to H: Probable meandwinc: 1»1^и1аг1аЙ$ In a 2 5-уеат-о Id
wom an w ho first noled loss of central vinion irr Ibe light eye?
Й1 л^е tb years. Ibis was associated with serosa n^ui nous ret­
inal detachment in the righl гилci-uI c™ d multiple thonOldaJ
legions superotemporal Id the macula, including the e le c t e d
white lesion seen in f. H e r Тахосага E L liA lest was positive.
Нет visua3 лс-jity Fttiprpved and she was asymptomatic uni i I
9 yeats later, w hen she had 1есиггегьсё of symptoms in the
lip Ml eye. ND№ 1be hypertrophic scar surrounded i*y л shal­
low suruus; retjfial delachm enl (large a rrow s, С. and H i anti
the Lrack-iifce pattern ol scare indicating ргоЬаЬГе гтю^е-
ment arrow s, C.1
!! o f vvoTm уел re previously -C]|. The
farva was prxAably encapsulated within Ihe large scar in the
sиp w o lem рогаI гласчНГ лгел tfargv jr^iows, Ci and l-li. This
яслг аррелred to contain е л к ш т tiilrastH^o^rafjbicaHy.
U Flofipbefni infLimmatory тл^и causirji л n rnt:Lilar bole Hind
m acular disp]aLemen( in a boy w ilh presumed Jiraoca^u
granuloma. Note demarcation lines caused by previous reti­
nal deLicFimenl.
f and К: Голослгл granulofrta pjosterior to tfie iris and cili­
ary body of a child who preKonled with л white pupiT. Note
Lhe eosinophil»: grdh|j|omas {arrow s, |ld one of which con­
tained the {охскагл ;лг\'л [WjSrte ^rr«w>, shown in higher
ptiwer in. Jt.
It ? iih:! b Ir u t n H ire! t'l u l | i'.il'I з Ixjc E w i l h р н лигы м ти п Г т с п ; lh e
A f Y IW iC ih 11j ij гI , . 11 -Ij Г i U | ? h Г hi .t Itti >::■I l i v : e ftp v v ig h t I л- Ih t: G | ) h U i i i l m k
11■11■I: ■11 1 C l i . I
ЕЪе clitiical finding of a localized subretinal exudative
lesion in the macula or a localized disciform scarr usu­
ally associated with retinochoroidal anastomosis of one
eye of a child with no other e vid en ce o f ocular disease,
should suggest the diagnosis Cif Toxccam ctEnfs. It must be
Femembered. however, that occasionally focal areas of
retinitis associated with toxoplasmosis may also produce
a proliferative sub retinal scar that resembles in every way
that produced by r^wpLismd (see Figure I0.23r K). Bilateral
disciform detachmenLs occurring tn children are unlikely
to be caused by То\жипт fdiFEj'j. In such a case, olher fam­
ily members should be studied for evidence o f a macular
dystrophy, ierous and hemorrhagic disciform detachments
in children may occur occasionally as a complication of
Best's vllelliform disease (see Chapter 5 )r other hereditary
dystrophies (see Chapter 5). rubella retinitis (see p. 918),
and diffuse unilateral sub acute neuroretinitis (see pp.
864-872), and in patients with idiopathic panuvetlis, vlt-
ritis, and multifocal chorioretinitis (see Chapter l l j .
 I [Ls Kj рлthoLoyicalIv, material left in Lhe wake of the
migrating Earvae may cause a strongly eosinophilic granu­
lomatous reaction along its path, lhe organism is usually
identified In the center of an eosinophilic abscess (figure
10.26, E and j^< yim 1s75139i »7 0 ш |н1Г toXoctirjjsis has
been produced expert mentally.' 1' ' :7
There is no satisfactory medical treatment for ocular
Tbxocdlra cauts, Photocoagulation may be o f some value iit
the treatment of subretinal granulomas in the paracentral
region causing macular detachment. Vitrectomy proce­
dures have been used successfully in the treatment of re ti­
ll.l! detach m a n :.-.ч r..ued wilh vicunus Lr.ktkm слш гd
by inlravilreaE or more peripherally located subretinal
g r a n u l o m a s . ^ ^ 1*
CYSTECERCOSIS___________________
Cysticercosis es caused by human ingestion of the eggs of
Taenia soiium (pork tapeworm). The egg£ disintegrate in
the gastrointestinal tract, the embryos invade Lhe intesti­
nal wall and are carried throughout the body, where they
undergo metamorphosis Lo become CyjfiVtficjjj cellu lo-
sn? (Figure 10.17, A). Most patients have several Larvae in
the body though only one may be seen in the eye. Often
larvae are seen in the brain and subcutaneous tissue.'101
Some o f the integumental and brain cysts can calcify and
can be detected by plain X-ray o f the abdomen, forearms,
and skull. Seizures and headache may be the presenting
signs of С Kb cyslicercus. 'ihese larvae may enter the eye
(more frequently the left) by way of either the central reti­
nal artery or the ciliary arteries.: ' "Jl 'they may gain
entrance lo the subretinal space (figure 10.27, В and C),
the vitreous cavity (figure 10.27, G), or the anterior cham­
ber (figure 30.27r IE). Over a period of many months they
grow into a targe cystic structure. W hen they are located
beneath the retina, they may be mistakenly diagnosed as
a serous detachment o f the RPh or retina, as a choroidal
tumor [Figure 10.27, В. C. and -ки.-ки or a
retinoblastoma.'11"
Recognition o f the white head or scolex that is often
invaginated and moving within the cystic body permits
accurate clinical diagnosis (llgure S0.27, A-С). lhe scolex
reacts and moves lo light shone into the eye. Eichography
may be helpful in localization and differential diagno­
sis in some cases associated with retinal detachment and
vitreous opaciftration.17J,,40e Multiple organisms т л у
occasionally be found in one or both eyes,-^-""*3 Enuring
its early growth the organism may incite minimal reac­
tion. Eventually, however, secondary inflammation, usu­
ally caused by the death o f the oiganism, may destroy the
eye, or leakage o f cyst fluid through the wall may cause
inflammatory debris, Lxlraocular locations often seen are
ill the subconjuncliva, along the rectus muscles, eyelids,
and in the orbit. En endemic areas ocular involvement
t fj.2 7 Octi Ear cys Ifce rcosis,
A: D raw ing of E V s f^ p C J^ cefttrfos ae lartae vvilh Iht? scolc?.
BKlendeiJ and invagim lud I г .
В lo F: iubrelinal CystjtQfiiiJS Luva in а 7Д-year-old w om an
from HouLh F Icjti-cin. Sim com plained cil progressively worsen­
ing ffoaLers. in Lhe left eye Ы" 5 months" duration. Note Lhe
inva^inaLed scolex U m jw ii and change in shape of lhe cys­
tic eit. us in lhe jflibretinal space inferior to lhe left m acula iH
find C). Laser photocoaguEaLion appficalions were placed
around Lhe organism several days liefore Ms surgical removal
by lhe Author via a posteringIf scJeroLomy and choroidoJomv.
NoLe [He rinц. o f pho*ocofl^u3aLion Hcnrs iind lhe sclerot­
omy scar i.3J and l&ttuw, hi several weofcs after ils removal.
Photomicrograph □! lhe cysticerfcus IFI shows inva^inaLed
scoltji wiLh booklets [u p p e r atr&wY and sucker iWnver arrow'..
Нет visual acuity was 2(1/20 1S monlhs after surgery.
G : 5ubretinai Cfystit& Cps w ith scales. extended anlerFurly
LhrtUjtijn lhe foveaI Cerijjpr into lhe vilroous. Ш аек a rro w indi­
cates sucker: w h ite a rro w indicates rinji; of hooklets.
H and I: C y s lic e rc u s in lhe anterior chamber.
|: iubretina! C y stice rcu s with invaginaLed scolex in
a 6-year-okl patient whose -eye was removed wilh lhe mis­
taken diagnosis of rolinobiasloma.
\ C f r i i n i H-.II *1.1 n i t " - - : 11. L O L T ltfS V 1?Г J. А г Ч С I, r iU U r lL 'b 'j L J r M y h O ¥ l У;|Г1СЛ ||.1
is encoutitered most frequently during (he early decades of
jife/IJ:' though о Lher studies have found Lhem predomi­
nantly in the third and fourth decades.'11-' I here is a male
predilection of 2 : 1 , suggesting thal workingmen are more
exposed lo unhygienic food and water.'"-1 Almost 3 0 % of
affected individuals are vegetarians; hence contaminated
water and uncooked vegetables may carry the eggs in addi­
tion Lo poorly cooked pork. Approximately one half of
patients will show evidence o f antibodies to cvsticercus.
The infest aLi on is common in Mexico. India, Pakistan, and
oth er develop ing cou n tries.:u1 •*14
iiecause o f the predilection for in lamination after death
of the organism, surgical excision o f the living organism is
(he ideal treatment.4 ' L! ' When located in the far periph­
ery o f the eye, the larvae may be removed transsclerally
(Mgure 10.27, B - E i) . Transscleral removal of larvae locaLed
in the posterior pole is difficult. Photocoagulation of small
larvae (hat do not exceed two disc diameters in si^e has
been reported by Вагелте. 1 Ш 4 L-.ven when small, how­
ever, photocoagulalien treatment results in considerable
inflammation and scar tissue reaction. When in the vitre­
ous the organism may be removed by vitrectomy. ^ - 110,4]S
Fven though it is best to remove Lhe organism intact,
meticulous washouL following accidental rupture dur­
ing vitrectomy has resulted in preservation o f die eye and
visual recovery. All patienLs should be evaluated for addi­
tional extraocular cyslicerci.;:| Praziquantel is an anthel­
mintic used in treating intracranial cyslicerci along with
systemic steroids to quell the inflammatory response lo
(he death o f the organisms.
C ysh'cc meters Й6 3
DIFFUSE UNILATERAL SUBACUTE
NEURORETJNITIS
Diffuse unilateral subacute neuroretinitis (D U S N ) is a
cEinical syndrome characterized early by visual loss, vlt-
ritls, papillitis, retinal vasculitis, and recurrent crops of
evanescent gray-white outer retinal lesions and later by
progressive visual loss, optic atrophy, retinal vessel narrow­
ing, and diffuse EiPli degeneration occurring in one eye of
otherwise healthy patients (figures 10.18-
1>LJ5N is caused hy at Eeast two as yet unidentified species
o f nematodes: a smalEer one believed lo be the third-stage
larva o f the dog hookworm and a larger worm, the larva
o f a raccoon roundworm, that may wander in the sub reti­
nal space for 4 years or longer and cause progressive ocular
d a m a g e . ^ 21"1^ - ^
Patients may be seen initially during the early or sub­
acute stage of the disease because of persistent vitritis
and/or acute visuat loss in one eye: Vitreous celts are invari­
ably present but in some patients may be few in number
Jhere may be mild to moderate swelling o f the optic disc
in the affected eye. There may or may not be any other vis­
ible changes In the fundus at that time. Visual acuity may
be mildly or severely affected. A Marcus Gunn pupil reac­
tion is usually present. A few patients may demonstrate a
mi 3d clllaiy flush, anterior chamber cells, flare, and keralic
precipitates. An occasional patient may have a hypopyon.
Usua iiy within several days or weeks, careful observation
o f these patients will discEose focal, gray-while or yellow-
white lesions [with the smaller worm) and more gray-
brown [with the larger worm) with fuzzy borders that
involve the external layers o f the retina and RPE [E'lgures
10.28, A and D; 10-29, А, И, 15, V, G, and fr 10.30, A-C).
The lesions are typically con fined to a single zone, fre­
quently in the macular or juxlamacuEar areas. 'E'hey typi­
cally fade from viexv, usually within several days, leaving
minimal or mild ophthalmoscopic evidence o f change
in the underlying FtpEL Successive crops of these lesions
may occur from week to week in the same or adjacent
areas o f the fundus [E'igure 10.29) and in some cases these
tnay completely resolve only to recur again. Focal retinal
hemorrhages, perivenous exudation similar to that seen
in sarcoidosis (E:igure 10.28, J), and occasionally local­
ized serous detachment of the retina may occur. En some
patients during the early course o f the disease the visual
acuity may be normal or minimally affected. O vcf a period
o f weeks [larger worm) or months [smaller worm), diffuse
as well as focal deplgmentation of the KPL occurs (l;igure
10.28. C -lJ. These changes are usuatly least prominent In
10.2 В Diffuse unilateral subacule netiro re (in ft is
(DU5N),
A to C: Note the subreLinaJ motile nemaLode (arrows 1 and
lhe Subreitlijp! gnn—w hile infEammaLory lesions in lhe interior
portion flif Ihe macula cjf д 14-year-oJd Езоу w ilh acute visunl
loss in bis ri^hl е\ч!. Visual acuily was 21У200.
D to G : This young girl experienced nap id loss o1 vision in
the right eye and Was misdiagnosed as having acute poste­
rior multifocal placoid pigment epitheliopalhy. Nole Lhe
coiled subreLina! nemaLode (arrow; [J.. Angiogfaphy showed
ihe suEi-retinal lesions to Ere nonfluorescenl early :Ll anti 1o
stain Eater (F). Note also evidence o f retinal perivascuEitis.
The presence «Г die worm was unrecognized at lhe lime of
iniliiil и £ лт:п л[ю п . Twenly-eighl months later Ihe patient's
visual acuity was counting fingers only. Note Lhe o piic alro-
pEiv, narrowing 6 Г lire relinal vei-sels, and diffuse degenera­
tive (. I m i i ^os in the K l’ fc (C).
H nind I: Late slaves of U U S N in a 15-year-old black boy
whose visual acuity was 20/400. Nole lEre optic atrophy,
severe narrowing, and sheathing of lhe relinnl arteries (H),
nп-lI Widespread mol Lied depigmenLaliotl o f Ihe КГН w ilh rel­
ative sparing or lbe Rip tu la angiographically fl}_
[ lo L: Perivasculitis in a 27-year-old man w ilh mild toss of
vision in Ihe rigjil eye. The left eye was normal. The candle
wax-dripping exudalet buggesled sarcoidosis I .MedicalI
v a lu a tio n was negative. AngiogjapEiy revealed extensive
slain ing Four monlbs later the exudates bad cleared (U.
There was a vitreous tag \arm w\. pallor ol lEre optic disc, and
multiple ГосаЕ as welE as diffuse changes in the peripheral
hlh’t. Л 7 0 0 1mi m olile subreLina I nemnlode was found a I Ihe
equator and was killed wiLh argon laser. Six weeks later Lhe
visual acuity was 20/25- and Llrere was no evid en ce o f active
neliniLis.
11J - t i 1тнгп G.iss (;[ nil '1
the central macular area. Jhe mullifocat areas of depEg-
menLation, which are most numerous in the mid periph­
eral fundus, may simulate those seen in the presumed
ocular histoplasmosis syndrome.
Accompanying these progressive changes In the R PE Is
a gradual narrowing o f the retinal arterioles and increas­
ing pallor of the optic disc [Figure 10.2ft, D-l). Pigment
migration into the overlying retina Is uncommon. In many
cases, particularly in young children, the disease is not
detected until the defective vision is found on a school
vision examination. Choroidal neovascularization and
disciform lesions may occur in some patients. One young
twy in Florida was found to have large macular subnet Inal
fibrosis. Jn general, the degree o f optic disc pallor and ret­
inal vessel harrowing; parallels that o f central visual loss,
but striking exceptions occur.
 ThfiS disease is caused by a motile, white,- often glistening
nematode that is gently tapered л1 both ends and varies
in length from 400 to 2000| m, with its largest diameter
being approximately one-twentieth o f its length (Figures
10.28, A-D; 10.25, Ei, C r h and G; 10.30, A-D, and C-L;
10.31 7 II propels itself by a series o f slow coil­
ing and uncoiling movements and less often by slither­
ing. snake-like movements in the subretinal space. It may
be found during any stage of the disease and should be
Looked for even in patients with advanced optic atrophy,
narrowing of lhe retinal vessels, and degenerative changes
tn the RPli .'^1 lhe second eye is rarely affected; only one
such incidence has been reported.lJ* I'here are at least two
endemic areas in the United Slates for this disease. In the
southeastern United Stales, the Caribbean islands- and
Latin America the nematode varies in length from approxi­
mately 400 to 7 О 0 И Ш . 1 In the other endemic area.,
the north midwestem United Slates, and in other parts
o f the United States, it measures approximately 1500-
2000 |im in length (Figures 10.30, A-b; 10.31 j. Individual
cases have been reported from Germany. Venezuela, India,
Bangladesh. In rope, and Chana. ::: A careful search
with a fundus contact lens, a 70 or 90 diopter lensr is
required to locate Lhe smaller worm. 'I'he larger Worm is
relatively easy to delect using indirect ophthalmoscopy
and a fundus contact lens, lhe Worn) is most likely to be
found somewhere in lhe vicinity of active deep retinal
white lesions that probably are caused by a toxic inflam­
matory reaction to material left in the wake of the wan­
dering nematode. I'hese lesions and the worm are more
frequently located in the extramacular areas. The magnifi­
cation and wide field of view provided by a fundus con­
tact lens and the fundus camera are ideal for locating these
worms.
Fluorescein angiography in the early stages of the dis­
ease usually demonstrates leakage of dye from the capil­
laries on the oplic nerve head, lhe gray-white areas of
active retinitis are non fluorescent early but stain during
the later phases o f angiography {Figures I0.2S, 1: and t)
10.2 У. K). Prominent perivenous leakage o f dye may occur
in some patients in the earliest stage o f lhe disease (figure
Ю.2.8, tv), attd there may be minimal or no angiographic
evidence o f damage to the RPE. As the disease progresses*
greater evidence o f loss o f pigment from the PPb is m ani­
fested angiographicalEy as an irregular increase in the back­
ground choroidal fluorescence (E'igure 10.28, 1J.
The electro ret inogram in the affected eye is usually
reduced in all stages of the disease and often is moderately
or severely reduced, with the b-wave being affected more
than the a-wave in the later stages o f the disease.1' 1 122,4
Rarely the electrorelinogram may be extinguished.
The identification o f the worm is unknown. Serologic
tests for ТЗщдагл amis are typically negative. ,J0 The stools
are free of ova and parasites, bosinophilia is infrequently
detected. Ihese patients do not manifest evidence o f sys-
Lemic disease. A small nematode was excised by means
o f eye-wall biopsy in one patient (Figure 10.30, tj-E).
Diffuse unilateral subacule neuroretinitis.
A to C: This И-уеаг-old boy was hospitalized because of
^Jtra№cted ocular histoplasmosis or Ь з й й з ^ т о Ш . 14c bad
noted rapid loss o f vision in Ehe ГеП eye. O ve r a 5-week
period, crops of evanescent jjray-while subretinal lesions
appeared and disappeared (A) before a motile subretinal
nematode lapicnits, E3 -and <") was noted. The nematode dis­
appeared, and 2 years Eater the patient's visual acuity was
counting fingers only. H e had optic atrophy, some n-airowin^
o f the retinal vessels, and diffuse chnn^es in I ho КГЕ.
D Eo I: This young man developed acute visuaf loss in lhe
right eye associated with a le w vitreous cells and multiple
outer retina I lesions confined to Lhe macula of Ih e ri^ht eye.
These lesions obstructed choroidal Fluorescence early and
stained late {EJ. The diagnosis w as acute posterior placoid
m liIfifpcaI pij;men1 opithe3iopalhy. O ve r lhe nest 1 1 days the
crops of white lesions moved inferobemporally. The subreti-
naf worm \tirmw, [J, and j'n.teE,. F anti С ) Ш found in retro­
spective review o f photographs, and photocoagu Iat ion I . H :
resulted in a focal scar ([) and resolution o f lh e disorder.
I lo L: Tin is ] 6-year-old girl presented with a 3-month history
of visual loss in the ri^bt eye. Visual acuity was 20/40 and
Ihere was a 2 -I- afferent pupillary defect. Vitreous inflamma-
tiun and multifocal outer retinal lesions w ere present in the
rifihl macula. A subretina i worm wi5s suspet led fjm jw.. | bul
did nal show mavemenL. O n e week after 2 g thiabendazole
per day for 2 days, all o f the subretinal lesions had disap­
peared except for Lhe area of intense retinitis and vitreous
reaction ■'К l_. presumably caused by deiath o f the worm. Hive
inonLhs laler her acuiLy was 2 0 /2 5 , N o le Ihe st aj at lhe site
of lhe focnil retinitis tj.
IA - t h u m н:Г ,-.1. ' - ' . I- L I r u m <.1 e t , i l ' 4, L 9 9 .2 , A n w r iL ii n
M l i J i l .'i I A m c u i . lI j i i n . A ll S = e h rtt(.
Although there were some features that suggested the pos­
sibility of AnqApstoma £йлшшп* its precise identification
could not be made. 1'11 Cunha de Souza el al. extracted a
subretinal nematode through a retinolomy after pare
plana vitrectomy (Figure 10..10 , E.).|JU Unfortunately,
because o f poor fixation, definite identification of the
worm was not possible. Grossly it showed similar features
lo lhe worm removed in Miami,44U and to a 380|im Long
subretinal worm successfully aspirated from the eye of a
paliettL by Professor Kuhnt in 1Й86 (figure 10.50, K }.l,|L Dr
Dwight P . Uowman recently reviewed the pictures of the
worm removed by Cunha de Sou/a (figure 10.J50, L j and
concluded lhal it is most likely Ancylcsiama Mnrnuffi.4-1J It
is o f interest lhal three of the last 10 patients with a sub-
retinal worm identified at the Sascom Palmer bye Institute
had cutaneous larval migrans months or several years
before the onset o f ocular symptoms. Am'yfnsJrmkJ cuni-
a hookworm of dogs, is a common cause of cutane­
ous larval migrans in the south eastern United Slates. Ihe
infective third-stage larva of A. a m i?:™ is approximately
650 1:m in length and is capable o f surviving in host tissue,
including that o f humans, many months and probably
years without changing si^e or shape. I'n lhe second-stage
larvae of fJiii'JfiiTJCtTJ fs piorymis (larger worm], a nematode
found in the intestinal tract of raccoonsr has been sug­
gested as a possible cause for f > t J 5 N . A l t h o u g h
this nematode, whotfe larval stage measures ЮОО- 1500pm
In length, is a common cause for meningoencephalitis in
other animals, it has been Ш £ 1у incriminated in similar
disease in humans excepL a few cases In children. Ии-1М
lhe infrequent histt^r>r o f exposure lo raccoons and the
absence of CNS involvement in over 100 patients with
1>LJSN seeii at the Kascom Palmer tye Institute make
B*i}-?riiTSLjirj'j highly unlikely as a cause for LUJS.N in lhe
southeastern United States, the Caribbean, and Lalin
America .-1^ In L>LJ5N the siae of Lhe nematodes, lhe geo­
graphic distribution of reported eases, lhe clinical picture.,
and the infrequency o f serologic evidence o f infection with
T&ttfm a ccmis make it unlikely that T. amis is the cause of
D L IS N .
The pathogenesis of DUSN appears to involve a local
Loxic tissue effect oil the outer retina caused by worm
byproducts left in its wake, as well as a more diffuse Loxic
reaction affecting bolh the inner and outer retinal tis­
sues.1' ' :v Shis latter reaction is manifest initially by
rapid loss of visual function and alteration o f the electro-
retinogram, and later by evidence of loss o f (he ganglion
cells {optic atrophy J and narrowing o f the retinal vessels.
Optical coherence tomography has shown disruption o f
Lhe photoreceptor layer within xveeks of onset of visual
loss both aI Lhe site of the lesions and in the fovea (Figure
10.51, E, N. and O). Subsequently the inner retinal layers
thin out (E'igure 10.31, N). "lhe variability o f the inflam­
matory signs and tissue damage seen in these patients
suggests greaL differences in hosL immune response lo the
orgaLiism.
There are differences in the color o f Lhe lesions, the
motility speed, and the rate of progression o f the disease
between the smaller Amjiostouut ctwtmfrn hookworm
larva and the larger Bfiylisasatns ртисуапгз ascarid larva.
Jhe lesions caused by AntyJosiumd are gray-white [Figures
10.2S A. D, and J; Ш.2У, А. ]J, Q El, and K] and hence
more visible than the lesions secondary to floylfoucara
whejfe the Lesions are gray-brown and more difficult to
discern (ligure 10.51, C, 1, and I) lhe larger Worm travels
much, faster than the smaller worm. In lhe author's expe­
rience. those patients who harbor the B^Jiioscaris worm
show a more rapid rale o f progression o f the disease (the
vision dropped lo the 20,'У0 -20/100 level within a month
and to count fingers by 2 months} while in lhe patients
wilh the smaller worm, the visual loss was slower and took
approximately 4 or more months to drop lo the 20/'30-
20/100 level. A possible explanation for this phenome­
non is likely from the more rapid movement o f Lhe larger
worm resulting in widespread release of tonic products.
Childhood infection with £ау7£ ш т 1ф ргосдеиш can be
associated wilh neural Iana migrans featured by severe
neurologic degeneration. E-'our cases have been described
wilh ocular and neural larva migrans. lhe neural degen­
eration is progressive and widespread, with developmental
delay and cerebellar and cerebral degeneration resulting
in being confined to a wheelchair, incontinent, and fed by
gastrostomy tubes,453
Efi.3N Diffuse unilateral subacuLe nenrore(inftis
(DUSN).
A to F: These figures rElusLrate large subretinal nematodes
associated with D U S N in patients, all o f whom w ere from
Lhe mid western United iLales. A shows Lhe nematode
(am jw ) in a 6j-year-old wom an w h o experienced rapid loss
of vision in her right eye. В and С illustrate m ovem ent of a
similar-sized suhretinal worm |алгодо} in a 13-year-old bay
wiLh rapid loss of vision in the righl eye. Nole lhe binned
opl ic d isc m ai gi it a nd coarse rnol 11i ng qf lhe RP£. I J [q F i 11ut-
argon laser photocoagulation of a large worm Iu p p e r
arrow, [Jl in a 23-year-old man. Note IhaL Lhe S -shaped K P t
imprinl o f the worm [itnver a rm w , □, and arro w , E) in the
central macular area^ where :1 apparently had laiq fur some
Lime before moving superiorly, has disappeared in F.
G tu J:;iIi SLtbretinal fterin'atode (arrow) thaL initially was
totaled in lhe macula of an 1! H-y ear-old Puerto Kit.nr> E)oy (G).
Several months ialur lhe patient's visual acuitv was с о anting
fingers and lhe nematode had mi grain'd !o the fn'id periphejy
of the fundus. Reversed С-shaped applications of argon laser
photocoagulation ;H1 were used lo chase lhe worm anlerior
Lo Lhe equator. An eye-wall resection was done. No1e the
worm lying in- Lhe Hubnotinal space (arroivs. I and |).
K: In jjn u ary I SS6 Professor H. Kli hnL in Jena aspirated a
noma Lode 1rom the poslorioj vitreous eye ot a 3 1-year-old
man this drawing. K). He interpreted lhe worm, which was
О.З Я mm in length, as eilher a filarjal worm or adolescent
form o f Utrongyiun. In 19flb D r P C . Beaver's interpretation
of KuhnCi drawing was probable Toxocara ca n is (personal
comm Linical ion i.
L: This worm (600 ^jtm long and ЗОцгп w ide) was extracted
from lhe subretinal space via pans plana viLrettoniv in a
paLienL with the typical findings of D U S N . O n gross exam i­
nation it was initially inlerpreled as a probable Lhird stage
of Тйхосагц cxntt E>ul more recently has heen interpreted
а-s A fiC ylostom a салгл-игп. Unfortunately, lhe worm decom ­
posed Eiefore m icroscopic екап и л а!ion could be done. The
paLienL had no seroJogic evidence cjf having Ioxocaria^]s.
.iihl CJ Гт(1гп ;irul Hjniunituirr" . l'lti'i, Arnuri< , l i i Mrtlical
Д:л^x. .11:11п. ЛИ i :ц|-,1я resc^fctt L?-l- K ,it Kdymuncf l'I .lI.1- К frotn
Hu hul1' : L Гш т Cunh.i lit? Sui^Bl =L al 1 M: n\ "i i . li i.1 I
Only one eye believed to be affecled by EJ1JSN has been
studied hisLopalhologkally.'’ 1 ''' E'he eye was enucleated
15 months after the onset of the disease, which was clini­
cally suggestive o f lhe early acute and subacule phases of
E3LJSN. I his occurred at a lime before recognition o f the
cause o f this syndrome, and it is probable that the sub-
relinal worm was lost during sectioning o f the eye during
gross examination. IlistopathologEcally the eye showed
evidence o f a nongranulomatous vitrilis. ret in ills, and
retinal and optic nerve perivasculitis with extensive degen­
eration of the peripheral retina, mild degeneration o f the
posterior redna, mild optic atrophy, mild degenerative
changes in the RI>L. and a low-grade, patchy, nongranu­
lomatous choroiditis. No evidence of eosinophilia or a
worm was present. I'ailure lo find sufficient structural ret­
inal and optic nerve damage to account for (he patient's
light perception-only vision aL Lhe time o f enucleation sug­
gested that the loss o f visual function was partly explained
on a pathophysiologic rather lhan an anatomic basis.
 rhotocoagulation, the treatment of choice- is effective
in destroying the Worn) without causing significant intra­
ocular inflammation [E:igures 10.29, Hj 10.30, t; 10.31, J
Lind K). Locitinfi ihe worm, which is afWays found in the
vicinity of the w hile outer retinal lesions when they are
present, m sf require prolonged and repeated e^ainina­
tions. lhe destruction o f the Ancybstoimi worm is very
quick and complete with laser due lo its smaller size and
slower mobility. However, the lлгдег Ш ш с я ш worm is
far more motile and will run when laser touches it, hence
it is wise to Walt until it moves to an area some distance
from the fovea and use fairly intense While burns lo stun iL
and then complete (he laser photocoagulation. Obtaining
photographs o f lhe laser site post treatment is important
in ensuring the worm is completely dead; it often survives
and can move to a new area (figure 10.31, | and K). When
migrating in the suhretinal space, the worn] is relatively
isolated from the effect of orally administered thiabenda­
zole or diethylcarbama/ine, except in those patients with
moderate lo severe vitreous inflammation.J3< In these lat­
ter patients, thiabendazole has been successful in causing
death of the worm (figure 10.23, J- L ) .'4 'Lhe presence
o f a local area of intense retinitis and fading o f the other
white lesions 7-10 days after oral administration o f thia­
bendazole is evidence o f success of the treatment, and
is followed by rapid and permanent resolution of the
disease. Another strategy for treatment that has proved
successful in one patient, after numerous unsuccess­
ful attempts Lo locate the worm in an eye wilh minimal
inflammation, was the application o f scatter laser appli­
cations surrounding and within the zone o f outer retinal
white lesions to disrupt the blood-retinal barrier before
administration of thiabendazole (E'igure 10.32, A and ft).
Diffuse unilateral sub acute neuro retinitis is a great
imitator. In the acute and sub acute stages, it may simu­
late diseases associated with unilateral papillitis, papill­
edema, retrobulbar neuritis, and vitritis. W hen associated
with perivasculitis, it may simulate retinal sarcoidosis
(E'igure 10.28, J-L). W hen associated wilh active outer
retinal white lesions, it may mimic acute multifocal pos­
terior placoid pigment epitheliopathy ( l :igure I 0.2flr D),
D iffu s e u n ila te ra l s u b a c u le n e u ro re tin itis
( D U 5 N ) ( В j ylis j s c л г j s р л о е у о ™ " 5).
A jo О : A 5S-year-old physician noted a rapid unset of visual
lass associated with psychedelic pEiotopsias and deep dis­
comfort around lhe left pyfi Ы 1 -2 days' dura I ion. Нет visual
acuitv was 20/200. and she had small multifocal brown
lesions w ilh indistincl holders around iioLh arcades. A fluo­
rescein angiogram showed Ihese lesi-ons better and die ones
slraddlin^j Lhe inferior amadfe showed activity (Д anti B 1.
A diagnosis of M b W D S was made and she wai- kept under
observation. A lundus photograph done at that lime was
no*ed htily tor lh e indistincl lesions and Lhe coiled worm I ha I
was. present was nol noliced (Cf. The lesions w ere hypoauto-
fluorescent in lhe ben tat sUhtcfUpided by a hyper autofEuoTei;-
cenl border ([>:. Ап O C T through Lhe inferior foVfea showed
patchy loss and diffuse disruption o f lbi? pholoreceplors it -.
Her visual less, pbotopsias and eye pain conLinued and an
angiogjam 2 weeks later shows. new lesions nasal Jo the
disc nol present previously lFr a rro w s]. ih e was considered
Lo have alypical multiple evanescenl white dot svndrome
LViEW D S] and was offered consolation by an experl on
M E W D S . A w eek later Ihe patienl noled furl her worsen ing of
her vision and visual field. A repeal artfliogiam showed fresh
les’ons now straddling the ST arcade iC and Hi. Sfie w a i sus-
pedfed Iи have Lyme disease, and serology, lumbar puncLure,
and an infectious disease workup was performed. Lyme tiler
and C SF studies returned nejjaLive. Four and half weeks from
her lirsl presentation and aEjoul 12 days after she saw him,
lhe expert realized 1his co-aid he l-ler previous fundus
photographs w ere reviewed fciy the expert and her Jirsl ret­
ina doctor, Ejoth of whom Louid find Lhe large worm,
(tayii5B5c&iis p n n y o n i s in the pictures It). The fialienl was
a-sked Lo relurn to Eier firs I relina special is I who lasered the
worm (I). This worm moves rapidly compared lo the smaller
A iu vlosloina canfnum larva and is difficult to immobilize.
A photograph done immediately afler Lhe laser showed Ihe
worm was still alive and moving, I hough slowly I . Further
laser was applied 5mmedialelv and lhe worm was killed iК :.
The paLient's vision and visual field improved over b weeks
and I hen remained stationary. Her eye pain and pholopsias
nesotved withouL recurrence. Aulofluorescence and O C T
findings of photoreceptor ouler and inner segments loss
and relina I ih in n in g d id not change significantly Ifvt—O ). The
paLient showed parLial improvement in her vision anti visual
BeEd bv £>weeks, bul no further.
( C d t f T l f e y : П г № i L t ; r l W l ' i- i Il' I . -
serpiginous choroid tlisr evanescent г^,h Lie dot ш Л й Ц Щ .
BeKtpEs disease., multifocal outer tolopJ^nioste, and the
pseudo-presumed ocular hisLoplasEnosis зупф ош е (ligure
Ю.29. A and B). In lhe Liter stages it may be misdiag­
nosed as unilateral optic atrophy caused by retrobulbar
or intracranial. lesions, the presumed ocular hislopEasmo-
sla syndrome, unilateral retinitis pigmentosa, posllrau-
malic chorioretinopathy, and chorioretinaE atrophy after
ophthalmic artery occlusion (figure Ю.2Д, I] and J) Jt is
important to consider the diagnosis in patients with the
early findings o f the disease because photocoagulaLion o f
the worm will prevent further loss of visual function and
occasionally wilE be followed by visual improvement.
Il is imperative to suspect the diagnosis in those eyes
that do not seem Lo fit the profile o f multiple evanes­
cent white dot syndrome f.VlhWDS), which is most often
the misdiagnosis, since bulb diseases are unilateral and
'photopsia' is a common symptom in both. ]Ъе fluores­
cein angiogram shows mild hyperftuorescence early and
gels more intense in the late phase. One has lo think o f
Efi.32 Diffuse unilateral siibacule neuro retinitis
(DU5N).
Л .md B: ^caller laser applied to the quadranL w ilh recEwit
lesions from DU.SN whem Lhe worm could nul he found
on rm&at-ed examination. She? was given oral albendazole
for 3 days. Л photograph 3 d^iys later showed three active
lesions (arrows^ suggesting silts where the staggering w orm
ivKKvtjd to. hefafe dying.
Chorioretinal degenerative changes seen in patients
with onchocerciasis.
С lo C: Chorioretinal degeneralion presumed Iо he causcd
by onchocerciasis in an African. Note in lh e com posite ( O
and macular area 1D| of Ihe left fundus, lh e narrowing o f the
relinal vessels, palloj of lhe oplic disc, and lh e large geo­
graphic areas or" aLrophy and hvperpLinia of lhe RpE. Sim ilar
crin g e s w ere presen I in Lhe rrghl eye цbj . Angiography
reveals some loss of Ihe chonocaptllaris in lh e areas of geo­
graphic iilrophy :F and Cj ).
H t-o J: Sim ilar buL less severe changes with relative spar­
ing of lhe teifitral m acular area in another palienl w ill:
onchocerciasis.

L>U!iN in any palient diagnosed as M L W p S Wttti does not IA b . rL - p rin lc iJ w ilh p u i m i n i o n frtn tr L in p l.h A. t , u | j ( . L V I 'l i/ r h u r
C f t K h ji - r j 3 l.i h M I t r b J . U V je ft f c ftJd in t i Г л п о д гщ . U d J h i: la y p t t j : 2 Q 0 B .
improve wilhin 3 weeks, and if fluorescein changes persisL L u i.irltJt;.- If-J, D r 3 lu n h ft. liytfir
or new lesions appear after 3 weeks (figure 10.31, A. fr­
aud Ei ]. Questions about outdoor activity, cutaneous larva
migrans, travel to South and Central America.. Florida, etc. Symptomatically and ophLbalmoscopically this syn-
should be explored. Unless one has a high index of suspi­ drojne closely simulates some o f lhe tapetorefinal dystro­
cion, the diagnosis is missed until irreversible visual loss phies and begins 1-3 years after infection, ihe patient's
has occurred. primary comp] ain Ls are loss o f peripheral vision and night
blindness The primary fundoscopic findings consist of
FILARIASIS AND GUINEA W O RM Varying degrees of alrophy o f the H£Er choroid, and retina,
w ilh the most prominent involvement being initially in
These belong lo the same order and resemble each other the posterior fundus, particularly in the jujclapapil lary area
closeEy. Dirofilaria inhabits animals while humans are the and often in rather discretely outlined го лез temporal lo
natural hosts for Q fchcceffi, Loa torr, WuchererUi bancrofti, the macular area [figure ]0.32). 'Lhe chorioretinal changes
and Rhigia njaia)i. are secondary to the inflammation produced by the thou­
sands o f microfilariae in the choroid, and il is only rarely
ONCHOCERCIASIS that a worm is seen in the retina or vitreous. Jt is uncer­
tain whether autoimmune mechanisms play a role in the
Also known as river blindness, onchocerciasis is caused pathogenesis of onchocerca! сЬ о ^ н е НШН*.^1'15^ 13^
by a nematode filarial worm called Onchocemt L'o^tWuy. I'hese changes are usually associated with progressive pal­
It causes blindness and debilitating skin lesions infecting lor ol"the optic disc and occasional optic disc swelling and
more than 1 Й million people. 9 9 % of whom live in Africa, focal areas o f slight swelling o f the choroid, longitudinal
especially in Central and Eias-t A f i i f i *55_4|£г Wore than studies of lesions of the posterior segment in patients with
300 СЮ0 are blind and double lhal number are visually untreated onchocerciasis have demonstrated progressive
impaired, i'he remaining patients are in l.alin America: changes Lhal include live microfilariae, intiaretinal hemor­
Mexico, Guatemala. Brazil. Columbia, Venezuela, and rhages, cotton-woo I patches, intraretinal pigment, while
lieu ado r. lhe parasite is transmitted by small blackflies o f and shiny intraretinal deposits, R R i window defects, and
the genus 5глш/ш?н, which breed in fast-flowing streams progressive depigmentation at the edge of chorioreti­
and rivers, lhe microfilaria is deposited by lhe fly during nal scarring at rales Lip lo 200|im/year.!CV' Ivermectin and
a bloody meal and it grows into an aduEt worm in aboul mebendazole therapy did not appear to alter the progres­
a year. They live in Lhe subcutaneous tissues over bony sion o f depigmentalion of the scars.
prominences, lhe adult female has a lifespan of 12-15 'I'hese observations suggest that onchocercal chorio­
years and produces millions o f microfilariae when Fertil­ retinitis is associated wilh early changes in the retina and
ized by an adult male. 'Ihe microfilariae swarm inlo the and that the retinal disease may progress rapidly.
dermal layers throughout the body, have a lifespan of Angiographically, both the optic disc and the area o f choroi­
about 2 years themseEvesr and are taken by blackflies dur­ dal swelling show evidence o f fluorescein staining. Varying
ing a bloody meal. degrees of RI4! hyperplasia and subretinal fibrosis occur.
DisdJorzti detachment of the macula is not рлrt of the pic­
ture. E:eripheral visual field loss is often nut p f proportion
to the atrophy of the choroid and retinar and much of the
visual loss is believed to be caused by optic nerve damage.
Microfilariae Ш 0- 200ц т in length have been observed
hiomicroscopically within .ir beneath the retina in paLients
wilh nonnal fundi and visual function.'1 The fad that
organisms, occur in the choroid o f these patients who have
filariae throughout the both- does not necessarily prove that
they are the cause of the fundus changes, lhe observations
o f aarte transient multifocal :ireas of staining at the level
of the ftFK and progressive changes in the optic nerve in
Lhese patients following treatment with diethvlcarbamazine
citrate, however, lend some support to the concept lhaL
Qtidiocerra w/mhu is responsible for the fundus changes
occurring chronically in these patienLs.' 1<,J ihere is some
evidence lo suggest thnit these fundus changes may be more
prominent in patients who have received treatment over a
prolonged period of lime, compared to those who have not.
Ihus*. il appear Lhal onchocerciasEs, either alone or in con­
cert with some other organisms or genetic factors, is respon­
sible for a night-blinding disease and. In al least some
endemic areas, is responsible for severe disabling posterior
ocular disease, 'lhe pathogenesis of this disease tnay prove
to share some features with lhal of the pseudo-retinitis pig­
mentosa sine pigment! that occurs in patients with diffuse
unilateral subanite neuroretinitis (see pp. S^4-ii72).
Unlike dEethylcarbamazEnc, which quickly eliminates
microfilaria from the eye and is associated wilh reactive
and occasionally functional ocular changes, ivcrmeelin
eliminates microfilariae slowly from the anterior chamber
o f the eye over a period o f 6 months and causes minimal
ocular inflammatory react ion or functional deficit. Iliis
slow action o f ivermectin may he attributed in part lo its
inability to cross the blood-aqueous barrier"^' and/or the
mode of action of Ivermectin, which may inactivate (para­
lyze) rather than kill Lhe mierofilaria.'l" :’ 'k,!' A single dose
of ivermectin, lSfrjjg/kg, repealed once a year leads Lo a
marked reduction in skin microfilaria counts and ocular
involvement II has no long-term effect on adult worms.
Jhere is no significant exacerbation of either anterior or
1(1.33 Filariasts.
A Id F: A IS-year-oEd man living in India com plained of а
consign! flij.iltir w ilh smiku-liki* movements far 3 months.
There SVfls no дыsociлIejcJ vi-sual deficit. photnpsja, redness,
w atering prior OLuliar surgery, trauma, ur previous such epi­
sodes. И в hud increased Hippelile and jSjtomach ache. Hu held
eaten raw m eat a few days prior, and there was no history
of recent (ravel or contact w ilh pels. The vision in both eyes
was 6/6 with no inflLimmatoTV te a d i№ . Л () SIHJ long (5 mm
cylindrical worm w ilh an unsegmonLcd smooth fiody was
неи^п in Lhe V iln iu s cavity (A and E3 . iTie worm showed *low
intAieniE*i!Iн. There Were chofla№jinj(J atm phic patches in lhe
Гейna Angiogram showed Iransmission defects ib and
F: . SystEmic invesli^aliont, including s-1ooi raam ination, far
ihfou <i0t1SBCLrtfyS days were un геппл rkd hie. The Nvl1 worm
wan renttfiic-d via pars pinna iI reel nmy and w a j identified
□ dirofilarm.
G: StlbtaпjimtitfУй,t microfilaria in ;i paLionl imm Soulh India
endemic (ftr IVucApre/fa bancrofti.
Probable blowfly larva ( C a llip h o r f d a e k
H lo M : A JJ-vear-ald wom ai irom W e b e rn Pennsylvania
presented w ilh blurred vision in lit riцИI eye. Лп ova] yeE-
low legion Was s w n rnferoLemporal lo the optic disc (H). A
fluorescein angiogi^m was Interpreted as a cboroidril neo-
vascular membrane (I and J) and she received an intravfl-
neal injeclicn o f bevacizum ab. Three weeks laler her vision
improved lo 2 0 /2 5 . The lesion now lo oted like a linear track
w ilh a worm lhal h.id a centra! black line al ili .lnLoriur end
iК and I i. G v i t the пек! 4 weeks lhe worm moved further
IM l She was otherwise healthy. She drank unpasleutazpd
goat's milk and lived with jjoats, cat,, dog, guinea fowl, IrsJn,
and tur:lr„ and in liie broxim ity of w ild deer and turkeys. This
worm may be л first stage larva of C alliphoridaer a blowfly.
N : Internet public domain image o f CalEiphoridae larvae
uliijwing л black lino jn Iheir m iddle himilni Ю the n orm in
lhe patient's eve.
|f_oUrt«y: A-^ Dr Su 'i ! i М.и-.тц, tj. LJr ^.K. K.tlhnri.im; H-M Dr Hrjy
Fultci; N. W AliC Jtm .u r i d h ( M w ill. A, « h u , Vjniriuidj. L S w t n t t I . 11it:
Wetin.il Alliih, Siunrlr:it.20I IK ^7Н-П-7Сиа-Н320-^. p. 175..
posterior segment eye disease. IreaLmenl leads lo a marked
and prolonged improvement in ocular status. Safety and
effectiveness permit its use on a massive scale and it prom­
ises to revolutionize treatment o f this disease. "
 The bacterium Wofbachia has been known to infest
the parasite in a symbiotic relationship, decent findings
o f depleting the bacterium ИОДгасйм by use o f dosycy-
cline lias made the adult worm sterile and affected worm
development.
LOAIASiS__________________________
Ion is a human filaria endemic in central and western
Africa. The adult worm resides in the subcutaneous tis­
sue rather than in the lymphatics. Et sheds microfilariae
into the bloodstream and is transmitted by the bite of a
blood-sucking fly CliT}'sops. I he microfilariae mature in the
fly and move into its brain and proboscis, and are depos­
ited in a human by the bite of the fly. ihey are commonly
(bund under the skin causing 'Calabar swelling., that is.,
painful noduEes. The adult worm may be seen under the
conjunctiva and over the sclera, it is not known to migrate
inlraorularly. 'those patients thaL are coinfected with
Олс/ifLifiTdi and i.cw Im react with significant inflammation
when treated with ivermectin, resulting in severe neuro­
logic symptoms including coma. encephalitis, retinal hem­
orrhages, and membranous glomerulonephritis, 'Ihis is
believed to be from the rapid death o f a large number o f
microfilariae.11 Systemic steroids and supportive care
are required in this situation.1■2
DIROFILARIASIS
Jhere are over 40 species of D im file r ia in wild, (foxes) and
domestic animals such as dogs and cats worldwide. All
four species found in the subcutaneous tissues of humans
are accidental zoonotic infect ions: i?. лр?глзггг5 (dog heart
woritj), D. refwns, D. [raccoons], and D. trraj (bears).
Cases have been reported mostly in Lhe Mediterranean
region, Southern Lurope, the Russian Federation, Sri
l.anka, india. and the Middle hast, '['hough subconjunc­
tival and orbital locations are the common s i t e s . U L , D.
irpienj and D. fmrnirij have been removed from the vitreous
o f the human eys ^78-^ 1
In its natural host (he adult female lives in the subcuta­
neous tissues or the heart, and sheds microfilariae into the
bloodstream. The infective third-stage larva (microfilaria)
es transmitted into human subcutaneous tissue by the bile
o f an adult Cvlex or mosquito. Subcutaneous, sub­
conjunctival, and orbital granulomatous reaction is the
most common human manifestation.1'"-1' 587
Sometimes, the larva grows into a small adult and has been
recovered from the vitreous (E'igure Ю.ЗЗ, A and B), sub­
conjunctival space (Figure Ш.ЗЗ, d ] and anterior chantber
o f the e y e . [ he Worm can be in the subreltnal space
and the vitreous cavity. Chorioretinal scars are seen diffusely
all over the fundus; these do not typically look like (racks
that are seen with the maggots of the botfly (Rgure 10.13,
Et is possible that lhe dirofilarial larva moves around
haphazardly in the vitreous cavity and sub retinal space
causing the diffuse chorioretinal changes. The visuaE loss
1 0 .3 4 G n a th o s to m ia s ls .
A to С : faintly visible- macular slat iA) and i ntrav i I гад I
Cnatbjffithferfe iE and C ) in з young VifitnajTiese jjirl com ­
plaining of blurred vision in lhe ri^hl eye. Her visual acu ­
ity was -20/60. A /ro w s indicale lh e moulh of this ncmalodc^
whose body is filled with red blood. Note lhe stomal end of
lhe worm is attached Lo a vilnio-us strand. The worm was ini­
tially mistaken fur a partly occluded retinal vascular anom ­
aly. Thu worm was successful ly removed via lhe pars plana.
D and In tray il ген I j&nd [/?qsTc¥7J^ wtfh ampws indicating the
sloma.
Subretmal P o r r o c a c e u m o r H e x a m e tra .
F Ld I: This large subrefinal nematode was surgically
removed via (he pars plana in Eh is 27-year-old man w ho pre­
sented with a i -week hislory Ы blurred vision and ftaaLers
and a 3-day hislorv of only Iif^hc perception in his lefl eye. A
9000|ifli l[jnH nematode : a rrow s, Cl' was found in lhe suL>
iielinal Space at Lhe Lime of surgery. After a retiiKHumy the
nematode was ^гн^рсчЗ with forceps i}h and was extracted
from lhe eye. Ten months later Lhe vitreous was clear Щ and
his visual acuily was 2(MS0.
La rg e su b re tin a I n e m a t o d e о I u n c e rta in ty p e .
I to L: A long^ coiled, motile subrelinal nematode, estimated
to be approximately 25 mm long (arrows f was found
in the eye of this Latin Am erican air force pilot w h o noted
recenl loss of vision in his left eve. Note Lhe unusual pattern
ot fluorescein staining c l Lhe subreLinal exudate enveloping
Lhe nemalode. Several Wsejcs laLer, examination in Miami
revealud a pigment figure in the left macula, and а: полпю-
tile, partly decomposed worm in the subnetina! space Iarrow s,
К and L- al Lhe Lcmipornl edge -of the IcM1 macula. K'ole Lhe
swollen end seamen! of lhe worm 'i.vma/i' j m r n i) and Lhe
small diameter,, lighlly coiled loopt Ы lhe worm [far#? arrow,
Ll. T belyp e of nematode could not be identified.
.Y-t .. ouurtVKyOr £Lt.ptмл Й. J-r.m --i-n. J>;mri t FrOmflathrlckE!L >1. ;
£-1Irum■ !i11■
>:111.1гI t4;il.-|IJ;
appears Lo be moderate compared to EJU5N worms, which
are m 1 toxic to the retina, and the ophthalmomyiasis from
bolfly liarvae where patients are often asymptomatic even
though the maggot has traversed the length and breadth of
the suhrellnal space (Tigures |D.35r G and H; Ip,36, A-[);
lhe adult D. itiunftis varies in letiglh from a few eenliLTieters
lo ЛЗсеп. Surgical remDV»] of the subconjunctival or intra-
vitreHil womn is the treatment o f choice. It is possible thal
the large intraocular nemalode illustrated in ]:igure 30.34
(|-].) may have beeci a dirofilarial worm.
BRUGIA MALAYf AND
WUCHERERIA BANCROFT!
Ihese are human filarial worms endemic in Asia, J.atiLi
America, and Africa, lhe adutl worm lives in the lym­
phatics of humans and can block lymph flow causing
elephaLtliasis. The adult periodically sheds microfilariae
into the bloodstream. Very rarely the microfilariae can
gain entrance inlraocularly, likely via the choroidal cir­
culation, and has been found in the vitreous cavity and
anterior chamber.-uu ' or the subcutaneous tissue of
the eye and orbit. '1'1 ,Uj: A case щ placoid pigment epi-
Lbeliopathy and retinal vasculitis causing neovasculariza­
tion of Lhe retina was seen by the author in л patient with
W. btincrafti microfilariae in hi ft peripheral blood, lhe cho­
rioretinopathy did not respond lo System it steroids nil one,
but did respond lo oral diethylcarbamazine citrate and
the subsequent retinal flftova soil лrizltj о n to pan retinal
pholocoagulalion.
GNATHOSTOMIASIS______________
C^ijf/fojtorfrcr sprp]i^tjrjjrrr is the most ccunmon species
known to cause human gnathoslomiasis. Others causing
human infestation areC. Frijp?V/up??r C. nfppcnicitnj^i G. defo­
rest. and recently C. bin uctfai turn and C. mtfJjysfrte.^'^^'The
worm is primarily found in Asia attd (Antral and South
America. The definitive hosts are cats and dogs. Et has
been reported in mammals in North America. iLs life cycle
involves three larval stages that develop in fresh water, in
the first stage, as a free-living form, it is ingested by cope-
pods and matures lo the second larva! stage. The cope-
pods are ingested by fish, snakes, and olher animals that
drink contaminated water. The worm completes its third
Earval stage in them. At this stage humans may become
facultative hosls by eating the raw infected intermediate
host. Second-slage larvae can nilso be ingested from eating
or Etandling raw fish. Outbreaks o f visceral and cutane­
ous migrans have been reported due lo consumption of
raw fish in certain areas.i№i‘!0t Et is at the third stage lhal
the larvae may migrate for many уеагъ in humans, caus­
ing inflammation in multiple organ systems, including the
skin, lungs. CNS. and eye (Figure 10.34r A—Ji).-u
N'ineteen cases o f intraocular gnalhostomiasis have
been reported and the worm has involved the posterior
ocular segment in six instances ■'['he com­
monest symptom is the sudden onset of a moving verti­
cal or curved floaler in lhe eye following an episode of
significant eye ache, ih e ache in the eye subsides wilh the
onset o f the floater. Visual acuity is usually normal or only
mildly affected, suggesting that, the Worm does not liber­
ate any toxins earEy on. The parasite likely enlers the eye
through the retinal artery at (he optic nerve head or else­
where. lhe head is Lhe broader end wilh a mouth pari
consisting of two broad lips with two papillae on each.
']"here are four rows o f 4Q-4B hooklels soon after the Eips.
lhe rest o f the body has transverse rows of cuticles with
minute spines, ihe worm attaches its mouth to the retina
and feeds off the blood vessels; one can see a blood col­
umn through its translucent body. 'Ilie larva is a list- most
o f the tiine and has been successfully removed by vitrec­
to my (Hgure !0..14, A -li),-11'0-^ ,1f' with recovery of vision
in most instances. A t vitrectomy, efforts lo suck the para­
site into a soft tip cannula may be mel with resistance by
its Lenacious attachment Lo the retina. Bleeding from lhe
sile(s) o f its attachment is aE&o common. A report o f sev­
eral relinal holes resulting in a retinal detachment by
liathrick el aE. alludes lo this fe a L u r e .O n c e the worm is
removed, no specific anthelmintic is necessary.
Efi.3:i Any i astro ngyliasis.
A ' A 2 7-vear-oId тплп in 1НлiIлr>c1 developed proffftj^filve:
visual loss in Elis left eye fur 3 weeks following eosinophilic
meningitis 2 months prior. He had a history of eating raw
Ftla s p . snails. Vision in this eye w h s l/200r with an affer­
ent pupillary defect, cel In and flare in lbu -anterior chamber,
subretinal I racks., paf-e disc, and generalized retinal pigment
epithelial Alteration. An immature male tfrustrCrtfgyJш слп-
tonensis was removed from lhe vitreous cavity by pars plana
Vitrectomy. His vision improved lo 2ii'20(J.
!c: A 3£>-vear-old Thai man losl vision in his ri^h: eye over
a w e e t Lo the 2/200 level. A subreLinai live parasite was
tra te d with diode Japer. H is vision improved lo 20/200.
Ophthalmomyiasis interna.
С to E: This asymptomatic 1б-уелГ-aJd jjir] had a visual acu ­
ity o f 20/10 bilaterally. H e r left eye was normal. Note the
crisscrossing tracks ihroLif’houl Ihe rij^hl eye. These Lracks
were demonstrated best w ilh fluorescein angiography ■;[) and
t . The m at^ol had Suited lhe eye.
F: 5ubmaci.ikir hemorrhage caused 1л' a maggot that h a s
migrated into lhe vitreous cavity.
tc: Maggot iyiri|i on the anleriur surface of lhe retina. Note
Lhe surrounding bubreLinal Lracks and the round retinal hem­
orrhages (arrows)^
H to |: Sul ire! inn I lracks in a black Vtbrtjan with a hislory of
lost of cenlral vision for many months in lhe rigtiL eve. Visual
acuitv Jn lhe right eye was 20/200 and m the left eye was
20^20. N o le Lhe crusshalched subreLina] lracks and optic
alrtjfphy ^n the riцhI eye :H and 3i; left fundus was normal ij;.
Nr) maggol was idenlified in Lhe ri uihI eye.
K: ican n in j" electrcm micrograph b f firs I inslar larva of lhe
rodent botfly, C u te re b rs.
L: Cuilerbbrj letftsctni bdtfly£
iA iirnE b. cuurLtif JJr i. Sii4iivv.il: I-. «.uurlc/w Dr Г.1-. Si nl.LL^ul |r:
Li, сии Мшу L jr V V .j. L irtia A rd ; H - l . u u L lttd y D r k.il;>l'. к d I .in и Irun I t:
I from (.'usli5 Ll a! '1; L Ггмгп hl.iirJ.1 I
OTHER NEMATODE INFECTIONS
OF THE EYE________________________
Coodart and associates have reported the success­
ful removal o f a ?m m nematode, eilher JfcrvuctfL^Eijn or
Hexametra, from the suhrelinal space o f j young man with
uveitis and total retinal delachmenl (Rgure 10.34, H-l).
lhe adult slages of these large ascarid larvae are found in
lhe stomach and intestine of carnivorous reptiles, birds, or
minim a Is. The larvae ordinarily develop within the tissues
of smalt mammals before becoming infective for the final
host. This patient probably ingesled the eggs from soil or
water contaminated wilh the feces of an owl, hawk, snake,
or other carnivorous final host.
Angiostrongyliasis
Ajr^fnsJrmi^jjj ttspitafteujti is very rarely seen in the eye,
and can be found in the anterior chamber, vitreous cav­
ity or subretinally. 1 l he palients tnay be asymp­
tomatic, mildly symptom aticr or present with significant
decline in vision, painr and redness. These patients can
have uveitis, subretinal tracks, necrolizing retinitis, disc
L J
swelling. papillitis, macular and retinal edema, retinal pig­
ment alteration. and retinal detachment.'0'11533 ЧЪе severe
pigmentary alteration is probably from inflammation of
the choroid and retina due to subretinal migralion o f [tie
worm prior to access into Lhe vitreous cavity. Jhe interme­
diate host is J4Js sp. snail and other aquatic animals, and
infection is acquired by eating raw snails, shrimp, and
monitor lizards. ЧЪе incubation period is between 2 weeks
and 2 months. 520-5“ -s-4
bosinophilic meningitis and encephalitis are olher dis­
orders caused by this nematode; Lhe latter is fatal. Et is
prevalent in tropical countries, mainly L'hail and, Vietnam..
Japan, Taiwan, and E’lapua New Cuinea, although ocu­
lar infestation has been seen occasionally in India and
Sri j|ajita^Jl-'!2i‘ г J leadache. associated C5E: eosino­
phil за, and serologic evidence of antibodies, along wilh a
history o f ingesting raw snails* help in making (he diagno­
sis. Most reports are from Thailand. Persistent headache
for more than 7 days and elderly age differentiate menin­
gitis from encephalitis. 'I’he A. amlonensis larvae are in the
meninges and subarachnotd space and cause inflamma­
tory damage. Treatment involves albendazole and systemic
#jelDldS4ljJU,5a5j5:i,7,:S26 ЧЪе worms in the eye have all been
removed surgically given the si/e of the worm.
OPHTHALMOMYIASIS_____________
Caltiphoridae
In lhe su miner o f 2009, three rases of a new larva I hat
measured approximately 2000 microns in length wilh a
characteristic central black line through ils middle {L-'igure
10.33, H, K-M ) were seen in Western Pennsylvania (two
in Pittsburgh and one in Williamsburg}. All patients were
asymptomatic or had mild symptoms. 4'he larva leaves a
track that is partly pigmented [Figure 10.33, K-M) and
seems lo move slower than the botfly larva that leaves sev­
eral crisscross tracks [see Hgures 10.35, Л -C, G, and! l-l;
10.36. A—] J . I here was mild inflammation al the site of
entry into the subretinal space With a decrease in vision
to the 20/50 level [E'igure 10.33, ! and []. Vision recovered
following one injection o f intravitreal bevaciitumab and
has remained a( 20/20. ЧЪе two other patients also had
a similar larva and were mostly asymptomatic since the
Lrack was away from the fovea in both cases.
In order to establish the identity of the worm, exclusive
search of the literature (both human and ve Leri nary J and
the Internet resulted in the larva being identified as possi­
bly Calltphoridae,. a blowfly larva (figure 10.33, N)
Ophthalmomyiasis Interna
lhe Lerm 'myiasis' describes the invasion of the living ver-
Lebrale organism by the larval form (maggot) of certain
flies in lhe order EJiplera. The larvae responsible for intraoc­
ular invasion (ophthalmomyiasis 1лДегпд) belong mostly
to those genera that are obligatory tissue parasites, that
is, those that exclusively require living host tissue for the
Ш .3 6 QphthaIftjamyiasis interna.
A Lo G : This 40-year-old asymptomatic: man was seen for a
Mniltfrje* eye examination far passes. The left funduE has several
crisscross Uacks nxnile by a liolfly larva (hat in vi«-it)le alon^
the i nferotemporal vessels <A-EJ. NcHe the movement o f [he
Earva with change in ib head position. By the Lime [he parent
returned after photographs, Lhe larva had moved Ю the s-LJ.pwo-
Lernpural quadrant where il was phalofcoaglll aled usinjj а Ш 1
цхееп laser (FJ. Л composite picture showing extensive excur­
sions o f lhe Jarva throughout the fundus v. i Ih tjuC causing many
symptoms I d . There ате two dtH hemorrhages on the disc,
H : Time-lapse composite photographs showing movemrml
ut a maggot urfow:- in Lhe subrelinal space. This- worm was
destroyed w ilh photocoiglilatidt) without causing si^niПсапI
inliaocLrlar inflammation.
I: A com posite photograph o f ar asymptomalic palienl w h o
was seen few passes. H is visuat acuity was 20/20. NoLe Lhe
extensive palLtwn of SUbretlttaJ !racks and (he clum ps of pi{“-
inentaLiun Lemporal Lu lhe m acula and surrounding 11к 1 opLit
disc (arruLvs). N o mafyjoL was visible in Lhe eye. The patienL
was -seen again several years lator, and lh e visual function
and ["unnli were unchanged.
Subretinal tracks cn Lytico-Bodig,
j and K: iutirelinal tfacks 4 and K' jprteumed to have been
caused by a fly maggot ir two Chom oro Indians from Guam .
NoLe Lhe fdead-end' Lrack U^row, [J.
L: Hislopnlholo^v of a traclc observed clinically ir a Chom oro
Indian s Ih jw s fiypopi^m enUlion of the piemen I epjdit'lium
(E)eLween lhe knows), a few siihrutina] piemen I-laden macro­
phages. and scime thickemnj; of Bruch's membrane.
iCiiurtL'sy: A - U , U r ^ u.in A M r u i.; H . U r L 'o n s - I.in u : N . 1 - i C i>I I from
L i.t r i .i '( I L l'y v ii ' ■ : 1 4 7 b , А п и . л г к ; т \ 4 d i c . i l Л ! о г к : 1 .|Г ю п . A l l i i ( J ;il s
r n e n r t d . I . 4 , : I K.. U r S .D [ ( l a m a s H .m l o n .i
completion, of their larval development, Ihese include
the caltler stieep. hon>e, deer reindeer rodent, squir­
rel. chipmunk, rabbit, and human botflies.111 Hies iden­
tified as causes o f ophthalmomyiasis interna include
Hypcdenna Enocfj, Hypodsrma tanindi, Cuterdmi sp...
Gastemphih& fn[6iJf?!iEJfj. H. шклЬАц Oedcmigena tamndit
0 ?sm;s о ф GodiJfomym flfifPjfrtj'i.wjcr.T, W/ijVrnffsJnjj f?ti rf*rr-
Frtfi, aiid Cr&ioehlirt cri&B&al^ 9,-5iJ ЧЪе rodent botfly mag­
got Culerrbm (E4gune I0.35r | and tv] and liypcidenmi are
probably responsible for most cases o f ophthalmomyiasis
inlema in the United ^ te s .^ - ^ is js .r je J hf eggs or Jan.fae
may be transported lo the h и mail comeai or conjunctival
surface by Lbe adult fly, by a secondary vector such as a
lick or mosquiLof or by the palienfs hands. Most patients
give no history of being struck in the eye by a fly. l be mag­
gots may either remain in the periocular tissues (oph­
thalmomyiasis externa J / or bore their way through
the ocular coats and come to lie in the anterior chamber.
posterior chamber or suhrelinal space (I'igures 10.33 acid
10 ^й) 53Г5Й,5&^!-555
ЧЪе reaction of the eye to the larval invasion var­
ies. Signs o f inflammation usually develop only after the
death o f Lhe maggot. In some cases the maggot gains
entrance into the subretinal space and over a period of
months makes many excursions back and forlh across
the breadth of the fundus, creating an unusual pattern of
crossbetching or ''railroad'' tracks in the R PL (Figures Ю.35
and tO.36]. 53'55D!i52-> During its entrance through the
sclera and choroid and its course beneath the retina it
may cause one or more small s.uhretinal hemorrhages (see
PlgUre 7.] 6, E>-K). In some cases it exits from the eye w ith­
ou t causing any symptoms, despite widespread damage lo
the ftPE in the macular area (Figures 1 ^ 5 , Л-С; 10.36, A
and b JJns" ,s - in one case a CuterebtH siaggat was found
til the conjunctiva of a hoy who presented wilh a subcon­
junctival and a subrelinaE hemorrhage and tracks.n^ En
some cases the maggot may die in the nubretinal space and
cause a localised toxic reaction and a scar. In other cases
it may enter the vitreous cavity, where usually it dies soon
afterward, probably from lack of nutrition, lhe inflamma­
tory react ion that follows varies from a minimal vitritis to
an intense endophthalmitis, lhe caliber of the retinal ves­
sels and the color of the optic nerve head are usually unaf­
fected; howeverr optic atrophy and visual loss may occur
in a few cases (Figure 10.35, Invasion of the cornea
has occurred. ' 1 Only rarely are hoth eyes affected, and
this occurred in a patient from C u a m >J‘ (see discussion o f
Lytico-Uodig after this secLion).
Linear and arcuate tracks in the ocular fundus should
aIW ays suggest the possibility of ophthalmomyiasis, '['he
tracks are less numerous and mo re easily recognized tn the
peripheral fundus, tn the posterior poEe the tracks may be
so numerous thal their confluence may be mistaken for
a variety o f diffuse inflammatory, traumatic, or degenera­
tive diseases affecting the ftPE); (figures 10.35, A; 10.36, A
and El). In such cases fluorescein angiography is espe­
cially valuable in silhouetting the tracks (figure JO.35, ft
and tJ). Although oLher organisms such as ТЬрасага ctuiis
(the nematodes responsible for diffuse unilateral sub­
acute neuro-retinitis] and trematodcs may migrate into
the sub retinal space, Lbey do not produce the widespread
pattern of broad К Hi tracks that are believed to be pathog­
nomonic for myiasis. lhe transverse rings that are present
on its body leave a characteristic track wilh crosshalchings
Jhe curvril inear depigmented bands or bead-like arrange­
ment of atrophic chorioretinal scars that may occur, usu­
ally at the equator in the presumed ocular histoplasmosis
syndrome (F O H S ) and pseudo-POHS, may be mistaken
for the tracks in myiasis.555 The author has seen two
patients with an extensive network o f subnetinaI fibrous
strands and demarcation lines following spontaneous real-
Lachment o f a chronic rhegmatogenous relinal detachment
incorrectly diagnosed as myiasis. Л positive cEinical diag­
nosis o f ophLhalmo-myiasis can be made only with visual­
ization o f the white or semi translucent segmented maggot.,
tapered slightly at both ends (figures 10.35, L M ; 10.36, A
and 13-Е].
In the presence o f significant intraocular inflamma­
tion, the initial treatment o f intraocular myiasis should
be directed toward the reduction o f inflammation with
the use of corticosteroids. If inflammation cannot be
'Ifi.3 7 Ly tic o -B o d ig .
A to C: This 43-year-old C uam ian gentleman With С bo mo re
ancestry friigrated to I he United Stales at ajje 2 S. Or* an
examination Гог possible welder's flash burn he Was Found
to h a ™ (racks in his left eye. His vision was 2 0 /2 0 O U . The
riglil fundus was normal. Tfie I efl eye showed subrelinal
Lracks, somu of which wen? dead-end lracks, IhroughouL lhe
posterior po]e. N o l$N a w as visible. He had grdrVuTi up near
a h eath in £]uam and had ген red cows. goals, and thickens.
He did not reta il an episode of visual loss, or being bitter
by an insecL. He h,id no evidence of neLinilogica] disease or
dementia.
Ophthalm om yiasis interna (Gedoelslia cristata).
I.) to C : A 21-year-old gardener presented in Nam ibia,
Africa, w ilh severe pain and redness in his right eye that
begat1! as soon ah a fly hovering in front of him darled into
his ri^ht eye. Ho had pnjptosis^ conjunclival h emorrh аэде^
and chemosisj and limitation of eye movements in all direc­
tions -IJl. His visual acuity was hand motions. The rinhl
I-_indus had a serous retinal dclachm ent and areas of
retinal whitening (E^. H e was treated w ith syslem it steroids,
lh e orbital uellulilis and serous detachment slowly improved
over a few Weeks wiLh visible subretinal yellow с urviIinear
lines IF I. Fun her resolution of the sulneLinaE fluid cleaHy
shows lhe subnet ina I tracks of the larvae (G). N o larva(e| was
visible and the pa lien I rs vision improved li) 2 Q/20_
H to j: This 29-year-old man was s«en in N am ibia 24 h after
а эдгау fly hovered in front of his eye and iew inLo it. This
was followed im m ediately by significant pain. H e had co n ­
junctiva] hemorrhage, chemqsis, injection, and limitalion of
elevation (H). The following day he developed severe orbital
pain w ilh s m ilin g , 5m m proptosis.. and an inlraocular preS­
sure elevalion Lo -lUmmHg. H e w,ls afefcrile^ H e d fv e lo|jed
progressive exudative relinal detachment over the пок1 lew
days (Ij. There! were subretinal whiLt dots and progressive
linear marks surges live of I racks Ca3¥ifl*S, У.1 and one site of
subnet ina I and epiTelinal hemorrhage no1 seen in lhe pic­
ture;. H e was trealed wiLh syslem it sleroids, iVprtnecLift;, and
pressure-lowering medical ions. An .41RI erf lhe b.rain and
orbil w<ls normal except for pTopLusis. His clinical picture
and serous rd in al dolachmenL resolved over lhe nexL coupJe
of weeks and vision relum ed Lo 20/20. CurviEinear tracks and
w hile dots remained la^fows f\- no larva was seen.
: t ; IJ Li г Г l: i y : L ] L o ] L? r I. S l LA.! r i c k : . m i l I J r l i n n * . 1» E r a n d C . I
controlled, surgical removal o f the maggot is indicated.
]f the maggot es alive and the eye is free of inflamma­
tion.. the clinician may elect to observe the patient care­
fully for spontaneous exit of the maggot from the eye.. If
treatment of a sub retinal maggot is elected, pholocoagu-
lation is probably preferable to removal of the organism
by sclerotomy (E-'igure 10. 5 h). lh e maggot should be
watched until it moves beyond the macular and ju>Uapap-
illary area before pbotocoagulalion treatment is begun. En
three patients treated wilh pholocoagutalion. no unusual
inflammatory reaction occurred, ■'or•c,^
 A pigmentary retinopathy si mu Ealing ophLhial jnu-
ш М в interna is endemic: in the native Chamorro Indians
(Figures 10.36* J and K; 10.37r A-C) . 't2 5Sfl" 560 Lhis reti­
nopathy is particularly prevalent in patients who also
tiave l.ytico-Kodig (also known as amyotrophic lateral
sc Ieros is-E^arkinson ism-dementia complex of Guam).
No maggot has been observed in any o f these patients.
] lislopathologic examination of eyes with lhe tracks has
revealed focal attenuation of lhe R]?bi hut no evidence of
inflammation or a larva (ligures iO.Jfr, L; 10.3<<A—
Population surveys in Guam suggest that all of the palients
wilh lhe subrelinal track-like Eesions are 50 years o f age or
o ld e r .' Other than the frequent association of relinopalhy
in patients with l.ytico-IJodig, there is no other evidence
that the retina and CNS share a common eLiology. "lhe
pathogenesis o f both disorders is unknown. Ihe remark­
able similarity of the retinopathy to lhal in myiasis suggests
that il may have been caused by a fly that was preva-
lenl in Guam before the Japanese occupation in World
War EE. Unlike the tracks in patients wilh ophtbalmo-
myiasis, these tracks do not have the cmsshalehings. Ihe
decimation o f livestock and olher wildlife hosts during the
occupation, in addition to the widespread use o f insecti­
cides at the end o f lhe War. may have eradicated all of the
botflies, which are no longer found tn Guam .'0"' I'hese
Lracks are strikingly similar to lracks observed most recently
in patients from Central Namibia and other regions of
South Africa, suspected to be caused by the botfly Gerfwkfi#
cristata (see next section and figure 10.37, G).
Gedoelstia Cristate
111 is. is a botfly lhat inhabits wildebeests and olher bucks
in South Africa, '['he adull female Lays eggs in the conjunc­
tiva and nictilaling membranes o f the natural hosts. The
eggs hatch into hrst-slage larvae and burrow into the ret­
ina and optic nerve, then travel to the dura and subdural
space via either retinal and choroidal vessels or the optic
nerve. From the dura they travel through Lhe cribriform
plate or other orifices in the skull into Lhe upper part o f
the nasal cavities. In the brain they malure into second -
stage larvae and in the nasal cavity into third-stage larvae
up lo 25mm long. They are snorted out into the air and
fall on lhe ground and pupate, then hatch into adull flies.
Occasionally the fly can lay its eggs in humans where the
life cycle is likely aborted at the ocular level. Il is likely
that the egg£ that are laid in and under the conjunctiva
hatch inlo first-stage larvae, cause an inflammatory cel­
lulitis (l:igure 10.37, A and E) of the orbit, and choroidal
and subretinal effusion (figure 10.37.. bi.. С and ]:- ]l).T h e
[ (i.?•8 Int raocula r trema lodt\
A lo t : Subnelinai 1nematode сличп^ одгау Sijbretift^l exuda­
tion (arrow s, A i(j E) in the right m acula of a healthy 35-year-
old Asian man. Note evid en ce o f peripheral irregularly
plrirrienled Ith-lU ы (. л u sk?tI by The Irerrlat-aefe (A . The trt^maludt1
was destroyed with laser phoEocoagutalion.
inflammation responds to oral steroids; once the choroi­
dal effusion and exudative detachment resolve, several
subretinal tracks are seen (Kigure 10.37, D and I). These
lracks resemble the tracks seen in the Guam Chamorro
Indians w ith L.ytico-liodig fFigure 10.36, I and K}. No larva
has been found in the eyes with lhe tracks either in Guam
or .Namibia.
ECHINOCO CCO SIS_______________
Ifrenti й Л т м и ш lives in the intestine of the dog, from
which its egg£ may be transmitted lo the human stomach,
tram here the young em biyos penetrate the intestinal trad
and may be carried to various organs, rarely the eye. The
hydatid cysts have been described beneath the retina and
wilh in the vi ireous.': 1 ''
INTRAOCULAR TREMATODA
i'rematode infection o f the human eye is uncommon
and mosl cases have involved lung flukes
sp.). liver flukes [ftunbfo "■■l and schistosomia­
sis.''1'4 'Ihere are several reports of human infection with
the migratory larvae [mesocercariae] o f Ahemr in North
America and the eye was involved in three p atien ts.^ -1*0"
Ocular manifestations include pigmentary retinal tracks,
areas of aclive or healed retinitis, retinal hemorrhages,, and
signs of diffuse unilateral subacule neuroretinilis [Figure
10.38). lhe irematodes may persist in lhe retina and vit­
reous for several years afler onset of lhe ocular infection
[Figure f0.3S].Sfi6Aftfrm species occuras adulls in lhe intes-
line of carnivorous mammals. 'Itieir life cycle involves
a succession of three hosts: the snail [the first intermedi­
ate host), a tadpole or frog [the second intermediate host],
and a carnivore definitive hosl. lhe most common means of
human infection is by eating inadequately cooked fragsr legs.
Flukes are flatworms (plalyhelminlhs) - liver flukes
inhabit the biliary passages, lung flukes the respiratory
system, and blood flukes [iVAritastwra /гдел1л;Ыл',ы?и and
.S. rri(3f]WTti) the vasculature.
ftfjYTOnjJitt tIrfftflfo4ll
Schistosomiasis
Tremalodes Lhal inhabit lhe blood vessels o f humans are
referred to as schistosomes. Dickinson and coworiers
reported a unique case of eccentric multifocal choroiditis
that resembled acute posterior multi focal placoid pigmenl
epilheliopalhy and serpiginous choroiditis in .1 17-year-old
man with visual loss and an itchy rash on his forehead of 2
weeks'" duration. 1le had recently returned from'laruiania.1^'1
3listologic examination o f lhe skin lesions revealed ova of
ScJirsCtMorrrtf Иншил! Other rases o f Sfiftfcfosoma causing
subretinal p a n u ]o m i5M i ^ subconfunclival nodules, and
intraocular granuloma h^ive been reported. r,£,H,‘ib'J
Fasciala Hepa tica (Liver Fluke)
/гасЫд he{xi\icn is a zoonotic helminth seen in sheep-rais­
ing countries. Reports o f human infestation vary from 2.4
million lo 17 mi El ion. At least three cases of intraocular ^
hepatini associated with significant intraocular inflamma­
tion have been seen.S6J The patient presented with pain,
redness, and loss o f vision of IQ days' duration in the
Claspian sea region. The anterior chamber showed bloody
hypopyon and the anterior vitreous was full of debris.
A flalworm was seen moving in the anterior chamber.
Washout of the anterior chamber followed by lenseclomy
and vitrectomy revealed an immature F. hepatica. Jhere was
patchy retinal whitening, vitrilis. and vitreous hemorrhage.
Once the worm was removed and the debris cleared, the
eye quietened with improvement in vision to 20/200.
if?.3 8 C o n t in u e d
F to L: V iLrLbis and periphlebitis caused by a subrelinal
tranialode iit a heallby ЗЕ-уеаг-оЫ Asian nnan t omplniiTin^
of visual foss in the left: eye. His visual acuity was 4/200.
fqJlcwi-ng [reaJnbHi 1 with sub-Tonen's q&psufaj' corLkoste-
nt)ids bis vision impToved and irregular pigm^rHary tracks
became evident (Ff. Twen]y-one months a fief recurnenj epi-
sejde* ot vitreous inlbiminalion, a rnbtile trefnafesde Uirrow,
H; Lbat was encysLEhd was found iit the viLreou-ь (H) and wns
ruTnuved via pars plana vitrectom y The Irem alcde was iden­
tified as Aldiria mfisbflenraria :I j. Note lhe oral suckcr |УеЛ
amHvfc vunlral sucker In'jftoJ arro\.v\, and pL-nel rati oil у lands
(Pj. T h ep a lierl's visual acuity returned Lo 20/50.
I and K: A 10-year-old boy from a village in South India pre­
sented W'rtS; rtid it-ei'PS anti .г w hite lesion in bis ri^hl eye for
J monLhs. A whiLe jjranu Ionia Lhat was partly j’ liotic and
partly vascular was seen in the anterior tham lffii ot" the
rif^il eye, consistent with a U in ical diagnosis o f Cremated?
giajnutbrn-a,
J 1ГТНТ1 iVliL'tJrhjijlcl i-| :ir . I iLiid k , iCH jrN isy ut Or. S.U. h!:iLhin;un.
lhe eggs or metacercariae are ingested with uncooked
watercress or other aquatic plants, 'lhe metacercariae excysl
in the duodenum and migrate through the intestinal wall,
enter the liver and make their way it]to the biliary ducts lo
grow into maturity. Occasionally lhe metacercariae enter
lhe blood vessels and travel to other organs, and can enler
lhe eye.
V P л
Trematodes in South India
Kathinam and coworkere reported a series (41 patienLs] of
mostly young males aged 16 or younger [38 boys and 3
girls) with conjunctiva] allergic granulomas, occasionally
wilh anterior chamber inflammatory granuloma {figure
10.38, } and K). 'Ihirty-four o f lhe palienls were from a
single village. Surgical excision o f 13 granulomas revealed
a zonal granuloma Lous inflammation admixed wilh
eosinophilic leukocytes in nine; four o f lhe nine displayed
fragments of the Legumeut and internal structures o f a
trematode and Splendore-I ioeppli phenomenon (central
deposit of granular, acellular eosinophilic material sur­
rounded by eosinophilic leukocytes* epithelioid cells, his­
tiocytes, and Lymphocytes in response to foreign material
such as caterpillar hairs, tarantula hairs, synthetic fibers,
etc.). The remaining five revealed nongranulomatous
inflammation made up of lymphocytes., histiocytes, and
eosinophils. These children bathed or swam in the local
village pond and acquired the infection. Jhe trematode is
likely PhiiophlJiabrnti which has ihree intermediate hosts:
mo Husks, snails, and frogs. I"he infected birds lay eggs in
the water, the eggs hatch in the water lo miracidia lhal
enter the mollusks and snails where they grow into cercar-
iae.11 ' : Children swimming in the ponds infested with
these mol Lusks acquire the infection. Treatment is surgi­
cal excision of the granuloma if in the subconjunctival
space; intraocular granuloma may require topical steroids
and surgical excision. I’revenlion by avoiding swimming
in trematode-infested ponds is likely the most effective
method of controlling this infection.
RETINOPATHY ASSOCIATED WITH
RICKETTSIAL DISEASES
Kickeltsial agents are classified into three major categories:
the spotted fever group, the Lyphus group, and the other
diseases group.
Itocky Mountain spotted fever (RM5H) is an acute
febrile eczematous disease caused by Rickettsia richetl-
sii, a gram-negative bacterium transmitted by the wood
and dog Lick. It is not coeifined lo the Rocky Mountain
area, with nearly half o f She cases occurring in Lhe south
Atlantic states.' 1 i’atients present with fever headache,
and a maculopapular or petechinil rash on the extremities
that spreads centripetally to involve the torso lhe overall
mortality rate is between 3 % and indicating Lhe need
for prompt diagnosis and treatment wilh tetracycline or
chloramphenicol. Ocular findings that may accompany
[he acute illness include petechial lesions on the bulbar
1 0 .3 9 R o c k y M o u n ta in sp o tte d fe v e r {Rickettsia
r ic k e t t s fi
Л Iо 1: This 5ц5-ye a-r-crH man had a rapid duel int.1 in vision
la 2 0/20U in his left eye. H e had no lij’hl perception in his
right eye for 5 years ItjIlow ing д retinal dtfLachment. He had
я с. horioreLiniti* with serous relinal detacWrienl involving Lhe
lefl m acula '.A). An earlv phase an^io^ram showed ^ood reLL-
nal perfusion and pooling of dye in lhe laLe phnse fE3 and Ll.
The O L T ton-firmed lhe serous eleviition (D). H g had a nor­
mal complete blood count, H IV test was negative, and PCEi
Гот Н в ф е в ш Ш ег, H efp eS sim plex, and C ytt^ iE g a to v iru s was
negative. An inlecLLuus disease consultation did no1 yieEs дпу
clues. His vision loss com inued and Lhe lesion progressed
Lo involve the entire fundus with diffuse retinal vascular
ubsLrudion and choroidal effusion ■L—Ij. The vision dropped
Lo no lighl fxucciplion. His family doctor ordered a RfttfctLsia
Liter w hen he dlscovuTod LhaL Lhe palienL h.id been hunt­
ing prior Lo lhe- onsel ol visual symptoms, w h jth relum ed
positive.
LGtrtJttesy: LJr Li.ii.ir.ivbh.ih. Li J.iji.1I'l, АЙД. Viafvln-uiLic, L.iwrcn(.L' Im
Httinjl Alins, S.Lunriurs20ГС1, 97B-0-70JG-Jj:!G-y, p.^SJ..
con]undiva, conjunctivitis, anterior uveitis, papilledema,
retina] venous engorgement, cytoid bodies, retinal hem­
orrhages, and retinal vascular occlusion fig u re 10.39.
A-С and K-E-lj.'""'-^ 1 fluorescein angiography shows
evidence o f capillary non perfusion in the region of the
collon-wool patches, leakage of dye from the relinal ves­
sels in the vicinily of the palches, and evidence o f venous
obstruction [figure 10.39, b, C, and G). In exanthema Lous
cutaneous lesions, Lhe organisms invade Lhe nuclei of the
capillary7endothelial cells, proliferate, and destroy the cap­
illary endothelial cells. Necrosis o f the inlima and media
causes thrombosis and microinfarcts. Et is probable thal
lhe pathogenesis of the retinal vascular changes is simitar,
lhe fundus findings usually, but nol always, resohre with­
out causing visual loss following treatment of Lhe disease
with antibiotics such as chloramphenicol and tetracycline.
The illustrated patient progressed to no light perception
since lhe diagnosis was nol suspected until very late and
no specific treatment was given.
Similar fundus findings have been reported in other
rickettsial diseases, including endemic Lyphus.'"'11" :" '
'Lhe clinical suspicion can be confirmed by serologic test­
ing for KMSR Oilier organ system involvement can include
hepatomegaly, renal failure, disseminated intravascular
coagulation, shock seizures, fluctuating neurologic slatus.
coma, and death. A majority o f cases occur in children due
lo exposure Lo outdoor recreational activities and affmitv
lo dogs, and in hunters. !n fact, most internists order Lyme
and llicketlsial liters in cases o f suspected Lick bite.
Rickettsia Conorii (Mediterranean
Spotted Fever, MSF)
Aicfeefxsid conorii is endemic in Mediterranean countries.
IL is transmitted by fi dog tick Rhipicephnlus sanguineus.
Systemic signs are similar lo flM SF with fever, headache,
and а maculopapular rash Lbat can involve the palms and
soles. In one .series o f 30 patients (60 eyes] with serologi­
cally proven MSP, 30% showed chorioretinal involvement
associated with mild vitritis. One-third o f patients shoxved
changes on]y on a fluorescein angiogram Common find­
ings xvere retinal hemorrhages and retinal vasculitis involv­
ing the vessels on the disc, posterior pole or periphery
(figure 10.-Ю, A and h). Other ftndiEtgs were branch retinal
artery occlusionr cystokl macular edema. arteriolar plaques
similar lo Kyrieleis arteritis seen in ^шрШтпд, and serous
retinal detachment in one eye each. Ihe pathogenic hall­
mark is the invasion of the vascular endothelial cells by
[he ojg^nism.. causing endothelial injury and necrosis
[Figure 30.40, fi).
Treatment involves early institution of oral tetracyclines
in (he form of doxycycline; fluoroquinolones and clar­
ithromycin can be used if tetracyclines are contraindicated.
V IR A L D IS E A S E S
Cytomegalovirus RetinochoroicJitis and
Optic Neuritis
Although as many as 31% of adults have complement
fixation antibodies indicating previous exposure to cyto­
megalovirus [CM Vj, manifest disease is rare in otherwise
healthy individuals and occurs primarily in ihe unborn
infant and the inimunosuppressed patient.'">_Sia
Congenita] CMV Infection
Cytomegalovirus is ihe commonest o f all congenital
and perinatal viral infections anti occurs in 0.2-2.4^
o f all live births. rlhe fetus may acquire the infection
as a consequence o f primary (4 0 % ) or recurrent ( l % j
maternal infection. Ihe incidence is higher in lower socio­
economic groups. JrortunateEy only 10% of the children
are symptomatic. Prematurity, microcephaly, intracranial
L ' , i l i ' i l i i ' a l i i H i [ ] 4 T b v : i i r i c u l a r ) . increased t'-Si-' protein. 'h;i-
rio retinitis, optic atrophy, petechiae, jaundice, hearing
impairment, hepalosplenomegaly, anemia, and tbrombo-
cytopenia constitute the clinical features.
is shed in nasopharyngeal secretions, urine- saliva- cervical
secretions, and breast milk for 2-5 years and is the means
to demonstrate active infection. Most often Lbe chorioreti­
nitis is inactive since the children are immunocompetent.
However active retinitis should be treated with systemic
ganciclovir until the lesions become inactive. '"-
Efi.4fl Mediterranean spotted fever (Rickettsia conorii
retinitis].
A to D : A 20-year-otd man in Tunisia w ith a 3-week his­
tory uf fever and skin rash com plained of decreased vision
in the lefl eye o f 5 days' duTalion. Visual acuity wa* 20/20
irigbL cyt1: a nr; 20/200 (left eye). The anterior se^menl in
bolb eyes, and fundus of I bn- right eye were unremarkable,
rbcite were 2 - vilreous tells in Lbp left eye. The fundus of
the left eye showed a superom acular focus of retinitis associ­
ated with retinal hemorrhages.. oplic dint edema, and hard
exudates in a m acular sJar configuration (A).- Late-phase fIuo-
rescein angiogram o f lbe left eye sllOfcvs byperflLiQreseehc-t
of the focus o f relinitis, diffuse retinal vascular leakage,
blockage of choroidal f lutfnescc-nte by ru1in-.il hemtm+iages,
and oplic disc staining Ht3r. O ptical coherence tomography
shows hyperrelTectiviLy of Ih e locus- of retinitis and a serous
nulinal defachmonl extendш й to the fovea 'XI). Л diagnosis
ol Mediterranean spoiled fever was confirmed by posilive
serologic testing Hantibodies to Rickettsia co n o rii by rndirecl
immunoflucifasDen^t). The padenl was lreaLnd With dosy-
cycline 200 mg per day and prednisone 1 mjykg per day
with gradual taper over a period of 4 weeks. Visual acuity
improved gradually. Four months after presentation, visual
acuity was 2 0 ^ 5 in the left eye. Fundus shows healing of the
nelinitis withoul scar formation, and resolulion of associated
findings (D).
E In I: A 57-vear-old wom an in Tunisia w ilb a I -week his­
tory of fever, headache, malaise, and lym pbocylic meningitis
complained of floaters in both eyes. Visual acuity was 20/20
in bolh оуеь. The rifjhl fundus shows Jw o small w hile relinal
Fesions juxJlavascular in location (ajroivs}. with associated
reflnal hemorrhages 'El. Lale-phase fiuo reset: in angiography
shows faint leakage of dye fr-om the supenotemporal vein and
oplic disc staining. Mole the presence of an area of old KPE
alteration inferonasal to the m acula (Fi. LaEe-phase indocya-
nine gn^en ItCIGl angiography sbuws mulLipk1 small hvp^fiij-
orescunl dots (arravfcs^ 'CJl. Note the livpufluoiescujTice o f the
area of old R PE alteration. The o cular findings w ere sugges­
tive of a diagnosis of a rickeiLhiaf disease. Serologic losting
confirmed the diagnosis of acute murine lypbus, <l ricki’lltial
infection caused by AVctettsj'a lyp h i. The patient was treated
with oral tetracyclines for 2 weeks. Two months later, fundus
(H) and fluorescein and IC<L^ (b angiographic findings related
Lo murine typhus had resolved.
LC fittfD K y : [Jr M 'Lim tj: K h .jn .i l .i h j
W] Ihe virus
 rostnatally acquired infections occur most ш ш ш о щ у
in immu nosuppressed individuals with the acquired
immune deficiency syndrome (AIDS; see p. S06)., renal
allografts, or systemic malignancies or while receiv­
ing high-dose corticosteroids. Approximately 30% o f
patients with A ID S will develop CM V reLinilis.,
Cytomegalovirus retinitis is lhe first manifestation of АШ5
in approximately 2 % o f pa Lien is and results in the initial
diagnosis o f AIDS in approximately 15% of patients. "J "
Survival after the diagnosis of AIDS may be significantly
shorter i f CM V retinopalhy is the initial manifestation
o f s y n d ro m e .1 The ophthalmoscopic features o f lhe
acute stage of necrotizing retinitis include multiple, gran­
ular. yelloxv-white areas that become confluent and are
associated wilh retinal hentorrhages, vascular sheathing-
and sharp margins separating the acLive area o f necrotiz­
ing retinitis from lhe surrounding retina (1'igure 10.4!, A
and p - C ). The fundoscopic appearance has been likened
Lo that of pizza. rlTte segmental distribution o f the hemor­
rhagic lesions along major retinal vessels may be mistaken
for branch vein occlusion Cyto mega lo virus retinitis
infrequently begins in the cenlral macular area.
Jhe retinitis spreads much like a brush fire, leaving an
atrophic retina and a mottled KE^L along its trailing edges
(E'igure 10.41, P- К J. Vitreous cells Enay or may not accom­
pany the retinitis. Cytomegalovirus retinitis infrequently
poses an immediate Lhreat to loss o f vision on presenta­
tion. Et is a slowly progressive, necrotizing reti­
nitis that appears bn either a fulminanL hemorrhagic or
granular pattern. As the infection progresses, lhe lead­
ing edge of the infection is followed by a healing process
Lbat results in a thin fibroglial scar. Small refraclile depos­
its and Larger ye!low-white plaque-like deposits occur
within areas of healed CM V retinitis. I'hese large plaques
do not appear calcified or refraclile., yet histologically
these fibroglial scars may be highly calcified {E'igure 10.41,
Eiarly spontaneous resolution of CM V retinitis
may account for chorioretinal scars found on initial exam­
ination of patients with AIDS.'-'"'1
Infection o f the optic disc and juxlapapillary retina is
often associated with severe visual loss [ELgure ]Q.41, D
and In some cases involvement of the optic disc
and juxtapapillary retina causes visual Loss as lhe result
o f inlrarelinal exudation and macular star formal ion
and with exudative macular detachment (Figure 10 41,
L)/... . Patients with low CD4 4 counts, usually less
than E00, are at increased risk for developing C M V retinitis
and HIV-related non infectious retinal vasculopathy.l,UU0(H
Huorescein angiography demonstrates evidence o f reti­
nal vascular occlusion and permeability alterations in
the areas of hemorrhagic and necrotizing retinitis {I'igure
10.41, band CJ.
Severe sheathing o f the retinal vessels appearing like
frosted branches o f a tree, simulating that occurring
In idiopathic frosted retinal periphlebitis, may accom­
pany CM V retinitis {Figure 10.41, G - l).595' ™ ^ 12 This
may be associated with signs o f vitreous and anterior
I (?. 4 1 C y to m e g a lo v i ru s ^C M V ) re tin i lis in p a iie n ts
r e c e iv in g c o r t ic o s t e r o id a n d a n ti m e ta b o lite th e ra p y
fo llo w in g ren a l tr a n s p la n ta tio n .
A Lo Г : This 35-year-old wom an noted pafacentTal scolo-
maLa in both eyes. In the right eye she had an active wedge­
■ shaped area of ifettnttis лssociated with Rerrttirrhages and
perivascular cuffing (A I. In 1he* I erfI eye she had lajfje
graphic areas, of chorioretinal scarring al sites of previous
reliniLis. Ani’ ioj’japhy of lhe area illuslraLed in A revealed
widespread l o I lapse of the? relinal vascular bed in che area of
acute retinitis, and muilipEe local areas oi staining w ithin Lhe
lesion (Й and <Z>. Lleven years laler, visual acuity in the ri^fil
eye was 2Q/200. ih e had expensive peripheral chorioretinal
scaning, vrLritis, and cyslord macular edema. The lefL eye had
a dense catarat I, and visual acu ily was bnly lij^h: perceplion.
Cytomegalovirus (CMV) retinitis in patients with AIDS,
D lo f : Progressive C V lV re ii nil is and oplic tMuritis occurring
over jt 2 -month period. NoLe Lhe extensive e\u Ha Li on inlo
Lhe macular area i]>i 1 monlh after lhe phefemBtih i n t , and
evidence oJ early reiiolulLon al Lhe reLinilis after ganciclovir
Lreatmcnl in F.
С Lo i: Frosted branch angiopathy accom panying C M V
relini Lis. th e fieri venous exudation js conlinuous along lhe
venous w all and is different from the peri arteriolar plaques
seen in acute relinal necrosis, where Lhe plagues are discon­
tinuous and are an Lhe arterioles (see Figure 10.44, В and Ы.
J and K: Thickened retina in which Ihe norma: relinal ele­
ments are replaced № exlens ive InffltraliBn of large m ono­
nuclear cells containing prominent inlra nuclear and
intracytoplasmic inclusions. Intranuclear inclusions Jowl eyes}
п-ге*ееп in the retinal cells (K 1 ! and wilhin lhe FiF^L iK2}.
chamber inflammation. fluorescent angiography shows
no occlusion or stasis but does demonstrate late leak­
age from the sheathed vessels. This perivasculitis usually
clears within several weeks after antiviral treatment/'10011
Corticosteroids may not be necessary.llU,',:1,1' 'Ihe C M V
retinitis, however, often conlmues to show evidence of
graying along its margin (figure 10.41, V-ll and I). Jhis
smoldering relinitis may extend slowly and is a sign of per-
sislenL activity. Cysloid macular edema occurs infrequently
in palients wilh A]EUS (F'igure 10.41, X], particularly in
those wilh less severe states o f immunosuppression.
Disc neovascularization may develop in palienls wilh
CM V retinilis> and it may regress spontaneously.0''' Laudative
and rhegmatogenous relinal detachment (i'igure 10.4], I.)
may com plicate CM V r e t i n i t i s . 1 , 1 Approximately
15-30% of patients with CMV retinitis develop a rheg-
matogenous relinal detachment. 'Ihe differential diagnosis
may he difficult because small or ragged holes may be diffi­
cult Lo visualize. (3° Patients with chronic vitritis ]nay lose
cenLral vision because ofcystoid macular edema.
] iislopathoEog^caiJyr the areas o f active retinitis are
sharply circumscribed from the normal-appearing ret-
ina.534j61l,fi22 The retina is thickened, and its laminar
architecture is markedly disrupted by the presence of
many enlarged cells containing prominent Cowdiy type
A intranuclear eosinophilic inclusions with surrounding
clear zones [Figure 10.41.. J], giving the cells an owl's-eye
ЦррСЙгааде (figure Ш.41, K1 and К 2}. The underlying
R PE is typically disrupted and varying degrees o f chronic
inflammatory celts are present in lhe underlying cbo-
Foid. Intranuclear inclusions may be identified in RPK,
optic nerve, and vascular endothelial cells of the choroid.
Llecuon microscopy demonstrates viral particles typical o f
the DMA viruses as well as prominent electron-dense cyto­
plasmic bodies(l23-U4
The clinical diagnosis is made by demonstrating virus
in the patient's urine and by a rise hi complement fixation
and neutralization titers, lhe virus can be cultured from
the anterior chamber in eyes with hypopyon,l",16,6yS-< '-'
saliva, buffу coat of the blood.. Lears^^^"'1 1vitreous, and
the r e t i n a . " ' " ' 1 [’olymerase chain reaction for C M V
in aqueous and vitreous fluid can be used Lo aid diagnosis
in atypical cases.
Dual infection of the retina with human immunodefi­
ciency virus type I [M IV-I) and CM V occurs but its role in
producing fundus changes or in the enhancement of other
infections is uncertain*'’1 1,1 Autopsy studies o f patients
wilh A ID S have shown evidence suggesting lhal bilateral
CM V retinitis may be a marker for H IV encephalitis.1'11
Jhese studies have failed to demonstrate evidence lhal H IV
is a cause for cotton-wool patches.
Ganciclovir is the treatment o f choice in patients with
C M V retinitis.SB* 5eSj5 6 1 80-90% o f whom
will demonstrate evidence of prompt resolution o f the
retinitis folloxving induction dosages of IV ganciclovir,
ihose with visual Loss associated with exudative detach­
ment often experience improvement in visual acuity.607'*01
Prior to the availability o f highly active antiretroviral ther­
apy (HAART), 30-50% of patients reactivated while on
maintenance Ganciclovir is a viral
static drug thal does not eliminate the virus or suppress
expression of all virus genes.6llW3ii ]i appears I о function
hy limiting viral DNA synthesis and subsequent packaging
of viral D N A into infectious units.11 'there is also evi­
dence thal decreasing the amount o f corticosteroid therapy
has a favorable effect on C M V retinitis in cases other than
AIDS. Approximately 33е!□ of patients with AIEJS receiv­
ing j^inciclovlr for CM V retinitis in the past demonstrated
evidence o f persistent smoldering retinitis, that is, graying
EfJ.41 Continued
L: fcbtejjtnдIOg£titjus retina.] riel achmenl occurring from small
breaks in lhe л пел of inactive relinitis.
M Lo R: A 44-year-old poofly com pliant man with cotton­
wool spots fr\>m H IV rotinopalby in both eve.1* fW and N:
developed bilateral C M V retinitis В months later. Further
spread and parLial resolution o f C M V relinitis in bcub eyes
occurred over lhe nexL 8 monlbs.
S to U: This 5 2-year-old wom an with leukemia developed a
patch of refinitis (5). She received systemic ganciclovir fol­
lowed by placemen I of a yanciclovir Implant iL'i. The relini-
tis beaJed with residual pigmented atid jjliotic scar,
V to An 18-year-old j^irl with acute lym phocytic leuke­
mia developed C M V isnligenemia. She was lrenled w ilh
ora I val ga neieJtwi r For a few inonLhs and bwilched to aci-
clovir. Four т о п Lbs laler she presented with floaters in
both eyes. Smoldering C M V retinitis w ith some healed
areas were noted in lioth eyes. She was in Efefntstion and
was; olf chemotherapy for the leukemia. Visual acuity was
20/20 in each eye. She received JV ganciclovir follow ed
by oral va]£$a п с iclovir. The legions became less active (V|
and evenlually resolved wiLh гея id и a I pigmentary changes.
Aulofluonescence ima^iny я hows pigment cpilbulial loss
nasally in the left eye (W j. Subsequently bilateral ganci­
clovir implants were placed. 6 months JaEer sbe developed
vitreous cells and cysLoid m acular edema 'C M E in her lefl
eye with decrease in vision to the 20/flC level. A fluorescein
angiogram showed petal Iо id pooling of tfye in the fovea :X:.
Topical prednisone acetate (our times a day over 3 months
resulted in resolution of vitreous cells and C M E due lo
im m u re recovery uveitis w ilh restoration of vision to 20/40.
Sbe had a cenlral posterior subcapsular ca larad actounling
fur the 2 Ф 4 0 visual acuily.
ll .ind K, r rjunt'sy Dr K,il|:h b.i^k.l
along margins of the zones of retinitis. The smolder­
ing retinitis may slowly extend without evidence o f other
activity seen in Lhe retina fig u re 10.41, P-R). tn some
cases. howeverr this persistent gray border may not prog­
ress and biopsy o f such lesions has shown no evidence of
viral p a r t i c l e s . S i n c e the widespread use o f antiretro­
viral therapy, this is mostly seen in developing countries
where НААД.Т is not universally available, t-'undus photo­
graphs and visual fields are helpful in detecting evidence
of progress Ion."51*11- i.i-lj
 IfitraVitfe^l administration of gandciovir appears Lo
be a safe and effective alternative in ihe management o f
CM V retinilis in patients with AlDS.39JrUS,643rt,<l ц j3 par.
Licularly useful in patients with severe neutropenia or as
an adjuvant for systemic therapy.' Sustained-
release intravitrea! ganciclovir in the treatment of CM V
retinilis has been demonstrated clinically,- experimen­
tally. and pathologically to be successful since its first use
til 19 9 G /'"'" Combination trealmenL with foscarnet
and ganciclovir may be helpful in the 10-20% of patients
whose C M V retinitis is resistant to ganciclovir alone/ J tion ol (Be eyus revealed hemorrhagic, retinilis [ t ) ; A pholo-
Side effects of ganciclovir therapy include frequent bone
marrow toxicity, indefinite IV treatment, and frequent
relapses on maintenance treatment unless used concur­
rently with НААКТ 'Ihe drug canno! be used with zidovu­
dine {A2T} because of bone marrow toxicity.:,|и-(,Гч ьн.ьм
Koscarnet may be used with A2Tr which may also have a
favorable effect on CM V r e t i n i t i s . Ganciclovir and
foscarnet appear to be equivalent in controlling CM V reti­
nitis and preserving vision; however, patient survival is
somewhat longer with foscarnet.''1 "1
The mean survival of patients With A JD S after develop­
ment o f CM V retinitis has increased since 1931.™'' The
Location of retinal lesions appears to have no prognostic
significance for survival, ITije Interval from diagnosis of
A ID S to diagnosis of CM V retinitis (median 9 months) has
not increased.
Surgeons often use vitrectomy and silicone oil in
the management o f retinal detachment in patients
with A ID S because this technique is effective in these
complicated detachmenls and the operating time is
reduced Disadvantages o f this technique
include hyperopic shift, reduction in accommodative
amplitudes, and cataract. i’he visual results after surgery are
generally poor and they continue Lo worsen after surgery.
Indications lor repair will change w iLb advances in medical
treatment of AI DS . ' 1 1 Ocular toxoplasmosis and herpes
rosier virus [El/V) are other causes of detachment in AIDS.
Retinal detachment occurs more frequently after H ZV Lban
after CM V retinitis. Use of laser treatment lo prevent the
progression o f CM V retinitis appears to be in effective/'
Herpes Virus Retinochoroiditis
H ie herpes family of viruses ( DNA vims) under a variety
o f circumstances causes a fundoscopic picture o f necrotiz­
ing retinochoroidElis lhal is sufficiently characteristic Lo
suggest strongly the diagnosis. I his family includes ihe
herpesvirus simiae, which only rarely infects humans.
Ihese viruses also produce a similar histopathologic pic­
ture o f necrotizing retinitis and underlying choroiditis. In
areas adjacenl to, as well as remote from. the areas of reti­
nal necrosis, intranuclear inclusion hodies may be found
by light microscopy, and viral particles by electron micros­
copy in Lbe retina, fiPK, and optic nerve cells. Specific iden­
tification of ihe particular herpesvirus depends on viral
cultures. immunofluorescenL histologic studies., and IX !к
I 0 .42 Herpes simplex retinoehoroiditis and
encephalitis.
A Id F: Thin 1!3-monlh-old Еюу had a 4-day his lory of leth­
argy and low-grade fevur accom panied by seizure? on the
second day of his illness. He was comatose on admission lo
the hospital. A lumbar puncture revealed 219 w hile blood
cells w ilh 6 3 % monocytes in [he cerebrospinal fluid: protein
was; 1R9 my/d L. CT scan revealed a left temporal lobe Eesion.
fundoscopic examination revelled mu I l.ifoca I areas □( reLi-
nitis, perivasculitis and hemorrhaye iA and B). The patient
died on [he fourteenth day of his illness. Gross exam ina­
nicrograph nhowod retina; necrosis, netmilis :tJ perivascu-
litis, choroiditis, and viral in iranuclear inclusions (arrow, EJ
lhaL were1 m<Bt common in the irm w nuclear layer. Llectmn
microscopy revealed intranuclear viral particles typical of
herpesvirut- (arrow, 1 :. Sim iiar findings were presenl ir> ihe
brain.
G to I: A Ьб-year-old man had л history o f right-sided herpes
zoster ophLhalmicus 4 months before developing visual loss
in the ipsi lateral eye. H is visual acuity was 20/50 O l ? and
20-'20 O S. Ixam m alion revealed irilis, viLri15s, and mulliplo,
slightly elevated wh ite choroi da I lesions in the right eye.
lA—I- 1ГТМП С ! j i l 1Л ,iI 197ft, Aitilth ,m i'vil-tJ-i .iI Asjubcl.ilIcm. All
п^Иь- n'btrvcid.k
for the detection o f the virus genome/"'1 Vitreous or cho-
rm retinal biopsy and culture may be indicated in palients
with suspected herpes infection or other infection, macu­
lar-threatening lesions, suspicion of malignancy, and when
the results are expected to influence therapy or patient
care. Ideally the specimen should be divided into three
parts for light and electron microscopy study immuno-
histochemistry. and microbiology and tissue culture.
Biopsy should only be undertaken if there is support of
an experienced im mu no pathologist and the availability of
necessary laboratory capabilities, including immunohisto-
chemislry, electron microscopy, and tissue тки те/1 " " Ihe
quality of the cytologEc material obtaitied froLTt vitreous
biopsy is probably simiEar in specimens obtained by nee­
dle aspiration and vitreous suction cutter aspiration done
without in fusion solution.^'11,665
H erp es S im p lex R etin o ch o ro id itis
] Eeipes simplex retinochoroiditis occurs most often in
neonates wilh herpes simplex encephalilis.u- i l-!'f,J" :,‘''1 it Is
usually caused by herpes simplex type 2 and is acquired
from the mother's genital iracl at birth. Ihe risk o f a new­
born acquiring infection from a mother with herpes infec­
tion is approximately SO^ii/1-0 Ocular involvement occurs
in approximately 209£ of neonatal infants with herpes
simplex virus {EISV). Et varies widely in severity from con­
junctivitis lo necrotizing retinocboroiditis.061' The reti­
nitis begins as ivtulLicentric areas o f retinal opacification
that frequently become confluent (figure 10.42.. А-Г).
ll is associated with variable amounts o f retitial hem­
orrhage. 'Ihe disease in in fan is is usually fatal. In some
patienls chorioretinal scars may be evident at birth.4"1
Hypoplgmei^ted skin Lesioiis, brain lesions, and quie I
retinal scan; su re st lhal inlraulerine infection prob­
ably occurred during the second trimester.'1 ' 0"1 hirst tri­
mester infection probably produces teratogenic defects.
Ihird trimester infection produces active neonatal HEV
infection. Lite ophthalmologic manifestations of neo­
natal H5V infection include optic atrophy, chorioretinal
scars, corneal scare, and £atajaGt.L~7,66J|,lr1'6 Coarse hyper-
pigniented areas may occur pre-equatorialEy in clinically
silent cases, 't here is a high incidence of ocular changes in
those patients wilh neurologic disease resulting from neo­
natal herpes simple*. Visual impairment in patienls who
are severely neurologically handicapped as a result of I1SV
infection is caused mainly by cortical blindness.''"'" b"
Herpes simplex retinochoroidilis may occur alone
or in association wilh encephalitis in both healthy adu
aru] il^ n o s u p p n a s e d p a te n ts ^ * ™
I ferpes simplex virus has been isolated from eyes wilh the
acute retinal necrosis syndrome in otherwise heallhy adult
patients with primary H5V-1 or recurrent HsV-l.5S7,*4!:
Magnetic resonance imaging studies may show evidence of
spread of lhe virus posteriorly to bolh oplic tracts and lateral
geniculate ganglia.I:' ' Ihus, the clinical disease shares many
features wilh lhe Von Sztly' experimental model for 3-LSV
retinitis in the moube.:,''J
H erpesvirus В
Herpesvirus simiae {herpes Ё virus} is an alpha herpes­
virus endemic in monkeys of the .Vljmztvr species, in which
it causes stomatitis and conjunctivitis451^ 1'''1 ' J '['he
virus is extremely virulent in humans, 7 5 % of whom die
o f an ascending myelitis. It may cause multifocal necrotiz­
ing retinitis, optic neuritis, and panuveilis in one or both
eyes o f humans.*0^62*'6' 2
HERPES ZOSTER
CHQRQjDOPATHY________________
Patients with primary (chicken pox) or secondary herpes
zoster ophthalmicus develop one or more focal creamy
while choroidal lesions that may be associated with serous
retinal detachment, retinal vasculitis, vitritis, cycloid macu-
far edema, and scleFitis (Figure 10.41, G_ij.-J5L^S],36:jS4,jS5
Jhese may be associated with early blockage o f fluores­
cence and late fluorescein staining. E'ocal chorioretinal
scars may develop afler their resolution. Iltey may be
accompanied by focal atrophic scars in lhe iris in patienls
after herpes rosier ophthalmicus.''''1 In some cases it is dif­
ficult lo determine whether the choroidal lesions are pri­
marily infiltrative or atrophic or hoth.. Ischemia related
to ciliary nerve infection by the virus has been implicated
in their causal ion in patients with herpes zoster ophthal-
micus.j"' 1,L An immune-induced granulomatous choroidal
vasculitis similar to lhat occurring tn the brain and oplic
nerve is another possible explanation.
10,43 He rpes zos ler-va rtcel Ia vi ru s ch ori oret in iIes.
A and B: This 37-year-old wom an with chicken pox devel­
oped episcEeritis, visual lass, exudative m acular detach­
ment, and focal choroiditis in the left eye. She showed rapid
improvement erf all si^ns and symptoms following treatmHi I
with aLicltrvir.
C: This paJienl suslained marked visual loss foHowiпй a
sc-vc-rс с-: " i i i l ' I ■hi k<n | и nen she was 1 \ i.--:i - )l
Heir visuai acuity was 20/200 bilaterally.
Ischemic optic neuropathy in association with herpes
zoster ophlhalmicus.
|j Lo f =: Acute Ions oi vision in lhe ri^M eye occurred 2 days
rifki development of herpes zoster орЫЬнНткчгн in this
40-yea r-okl HiV-posilive man with evidence of ischemic
oplic nee гор,H by and mild (.enlral vein obsLrm lion. hi is
visual acuity was li^ht perception and progressed Co no light
perception wiLhin several davs. D oppler studies revealed e v i­
dence o f sLertosis of lhe fephtha Imi с cirlury. M K I scan oi lhe
brain was fl^rmaF. Two monlhs later he had some anterior
chamber reaction in :bu riyhl eye. w hich was stiil blind.
H and I: Thin 7-year-old boy w ith a 6-day history oi her­
pes zoster tiphlhnImre, us bad acule loss erf vision caused by
interior ischumic opIiL npunapathy It-1:. His visual acuity
was 20/100. H e had a dense Superior alliLudinal scoloma
and marked conlraclion of the inferior visual liekl. H e was
treated w ith oral prednisone 50mg per day. Four years laler
ll), note Lhe o p lit atrophy. His acuity was 20/b0.
3 lo L: PhotomJ<irugraphs showing poM ischemic cavernous
atrophy of Lhe opLic nerve |J) caused by granulomatous arte­
ritis (K and L.J in a blind, painful eye removed from a pal i ил I
who had herpes rosier ophthalmi-nii.
Herpes Zoster Virus (HZV),
Retinochoroiditis, and Optic Neuritis
Most paltents with herpes zoster ophlhalmicus and
chicken pox demonstrate no involvement o f the choroid,
retina, or optic nerve. Nevertheless, there are several clinical
syndromes in which chorioretinal and optic nerve involve­
ment by lhe ILZV may cause severe visual loss.c"
Foca! C horoiditis
During the convalescent stage of chicken pox or herpes
zoster ophthalmicus an occasional patient may develop
one or more yellow-white placoid choroidal lesions
throughout the posterior fundus (I'igure 10.43, А-С).™$
Congenital Varicella Syndrom e
Infanls o f mothers who had varicella infection during
lhe second trimester may demonstrate, at birth or soon
afterward, systemic findings including bulbar palsy, mild
hemiparesis, cicatricial skin lesions, developmental delay
and learning difficulties, as well as ocular manifestations
including chorioretinal atrophy, chorioretinal furars liintu-
lating toxoplasmosis, hypoplastic optic discs, attenuated
eleelroreltnographic and evoked occipital potential ampli­
tudes, congenital cataract, and Homer's syndrome (E'igure
\G.13, C ).liai l"he H ZV tiler to IgM is typically negative.
l-h'rptr* Z o s te r LtptfgidcTpQiftif 899
Focal Retinitis, N euroretinopathy, isch em ic O ptic
N europathy, an d Retinal Vascular O cclu sio n
In children and adults lhe External manifestation of her­
pes zoster ophthalmicus or chicken pox зилу be associated
a ia s ib n a ily with optic disc swelling, micular star, branch
of centraE relinal artery or vein occlusion., and multifocal
retinitis [E-'igure 10.43, D -J),fia2-fie6 In children and adults
H2V can cause a granulomatous arteritis and an ocular
syndrome similar to lhal produced by cranial arteritis,
including ophthalmoplegia, ischemic optic neuropathy,
hypotony, phthisis bulbl, and contralateral hemiplegia
(E-'igure 10.43, j-K }:?7^ 167^
A cu te Retinal N ecrosis fH erp etic Throm botic
R etinochoroidal Angiitis and N ecrotizing
N euroretinitis)
I Lerpes zoster virus (varicella-zoster vims, VZV) is the pri­
mary cause of acute retinal necrosis, a clinical syndrome
that develops in one or both eyes of typical healthy indi­
viduals of all ages, herpes simplex virus 1 and 2 (LISV-I
and HSV-2) account for a smaller number of cases,
wilh the average age at presentation being 52.4 years
for V/.V, 44.3 years for !ISV -Ir and 24.3 years for ] SSV-
2.696 HSV-1 viral acute retinal necrosis generally follows
recent or rejnole herpeLic encephalitis.f,,JJC,,?' There has
been a rise in HSV-2 cases, especially in the late teen­
age years.' ]1'Й9:|-И5'ЕМ [t jji characterized by the develop­
ment o f mild anterior uveilis, followed within a few days
by vitreous inflammation, pain, occasionally glaucoma,
and usually a rapid decline in visual function caused by
a rapidly progressing occlusive retina! arteritis, necrotiz­
ing retinitis, and optic neuritis associated with progres­
sive inflammatory infiltration of lhe vitreous [E'igunes
10.44-10.46).i?y 6 n -tw -721
Efj.44 Acute retinal necrosis syndtnme.
A to F: Л 50-vear-old diiibeLic African Am erican man pre­
sented w ilh rapid decline in vision over 3 davs, elevated
inliaocLrkir pressure, several areas o f focal and cun fluent reLi-
nitis, and retinal rirterinl narrowing wiLh peri venous hemor­
rhages Al. His visual acuity was 2Q /|p in LEie affected eve.
A clinical diagnosis of herpetic retinitis and panuveiLis was
made, and he received oral va lacrd o vir (VattreH), follow ed
2-3 days ]^iLrdг by oral prednisone. Aqueous l*CK was posi­
tive for Herpes simples virus. Two weeks later there conlin-
uoh Lo be vitrilis: rceLiплI arteries show periarterial pJaqties
and sh ead in g (B). The multifocal Eesions are now confluent
in lhe [periphery and mid periphery arid 1». H e was con­
tinued on oral va la cid o vir and lhe prednisone was slow ly
tapered over lhe nexl b monlhs. At 5 monlhs lhe optic disc
is pale, lhe reLinal arterioles continue La h a w perianuriolar
plaques and sheathing, and lbe peripheral lesions show pig­
mentary changes and fibrosis it and F). His vision improved
to 20/50 jnfl al Iasi follow-up I here were nu relinal tears or
detachment.
G (o J: Extensive peripheral necrotizing rhinitis in a healthy
79-year-old m m a n . Note lbe confluent areas uf retinitis in
lhe periphery associated w ilh perivascular hemorrhage «Li
and Н/ and the patchy involvement posteriorly w ilb spar­
ing of the center of lhe п ^ с ш а (I). There was marked nar­
rowing of the retinal vasculature and pallor of Lhe optic disc.
The right fundus was normal. The retinitis resolved sponta­
neous! Seven weeks later, visual acuiLy wan 20/50. There
was complete closure of all o f the nasal retinal vessels (JЬ
and extensive closure ol lhe peripheral vascutaLure tempo­
rally. 5he m aintainEd thib vision over the subsequent 3 years,
when she w as lost to follow-up.
K: This man was blinded in both eyes by the acute retinal
necrosis syndrome several years previously. Note the optic
atrophy anti thread-like remnanls of the rulinal vessels
 The retinal whitening often begins in multifocal areas
that become confluent in lJi-е peripheral fundus (figure
10.44, A- I) 31 is typically associated with perivascular
infiltration. vascular occlusion, and hemorrhage (Figures
10.44, EJ-D; I0.4!>, A —LI , O, and ly). 'Ehe occlusive vas-
cuLilis may affect the major retina] and oplic nerve head
arteries posterior to the zones of full-thickness necrotizing
retinilis {figures 10.44. B-D; 10.45, A and D -f). Retinal
opacification rapidly spreads posteriorly, frequently spar­
ing the macula [Figure 10.44. f and I). Multiple posterior
white lesions occasionally occur early id the course of the
disease. These may involve either or both the inner and
outer retina. Marked yellow atheromatous cuffing, nar­
rowing. and occlusion of the major branch retinal arter­
ies may develop [figure 10.44, Br E, and 0 ). Widespread
necrotizing retinitis is the predominant fundus finding in
most patients; however, some show evidence o f extensive
retinal arteritis preceding development of large areas of
retina] necrosis (figure 10.4!>r ] and Q). In some patients
visual Loss is caused primarily by branch or central reti­
nal artery occlusion, and the presence of either an arcuate
pattern or diffuse retinal whitening and cherry-red spot
along with (he atheromatous changes may be misinter­
preted as embolic occlusion of the retinal arteries second­
ary to carotid artery disease™ j73‘3-J35 Some patients may
demonstrate a milder progression and severity of the dis­
e a s e . An associated scleritis with underlying choroi­
dal effusion is sometimes seen (figure 10.45, M and N).
fluorescein angiography demonstrates reduced perfu­
sion in the areas o f retinal necrosis and retinal capillary
permeability alteration, as well as evidence o f focal choroi­
dal Inflammatory cell infiltration and t£ETL damage in areas
uninvolved by retinal necrosis (figure 10.45, L>—J [). After
a few days the necrotic retina crumbles and sheds into the
vitreous and a sharply outlined pattern o f usually mild pig­
ment mottling is left in the area o f previous retinal necrosis
(figure Ю.45, H). Hven as the areas of retinitis are clearing-
the patient may experience further sudden and profound
loss o f vision caused by (hrombolic arterial occlusion
within or near the optic nerve head. In approximately two-
thirds of eyeSr large irregular retinal holes develop in the
necrotic retina and are followed by vitreous organization,
tractionr and extensive retinal detachment {figure 10.45,
К, Q r and R). H ie detachment typically occurs 6 -12 weeks
after the onset of the disease, ihe overall prognosis for
visual acuity is generally poor, xvith only 3 0 % o f affected
eyes achieving an acuity o f better than 20/200.
IJisk factors for severity of the disorder early in the
course of the disease are retinal arteritis, reduced elec-
troretinograpbic amplitudes, and elevated circulating
Eh .4 5 A c u te r e t i n a l n e c ro s is c a u s e d b y h e r p e s s im p le *
v iru s ty p e 2 (H S V -2 K
A 1o L: An t fi-year-old ^irl presented will> photcipEiaMa, pain
.1nlI redness, and a decrease in vision Го 20/40 in Ihe left
eye. SEie was diagnosed with anterior uvEitis and started on
Lupitrtl steroids find c y ^ p d le d p , Symptoms worsened over
tEie next 4 days and the vision dropped Lo 2U/80. A diaj=-
nesis of panuveilis with oplic nuuTili* was made, and oral
slfco id i a I HOmj; рет dray w ere be^un. She W as Inferred Ihe
пек! day w hen her vision had decreased to count finders.
Ce]Js were seen in the anterior ch-iunErer and vitreous ca v­
ity. along with a swollen optic disc, several J l t i » of retinal
whitening, m acular whiLemny and scallured hlot relinal
hemorrhages lA-t!, Cj. A diagnosis of acule retinal rtecrqsis
was. made. Angiogram showed occlusion at several arierr-
ules in Ihe mid peripheral fundus inferiody and inferonanally
113—F, Hi. Aqueous P C R was sen I. for varicella-zosler virus
WZV) . USV-1 and -2, and CVlV; and oral slurnids w ere dis­
continued and IV aciclovir was Ijejjun. By 2 day's the media
haze worsened and ihe lesions b e t a k e more conflueni
AtjL.ciu:- I"! 4 i Mr'i--:i ::)si:ivt i:ii I пн ■I i■
■t ■Inr
V Z V and H SV -]. Ora.1 steroid w as added a I 40m ^f and a
week laler the vitreous, cells had decreased, buE the retini­
tis w as still conlluen) with retinal infarcts !|). Ten days laler
the retina detached, with several large hoEes in Ihe ischemic
inferior retina confirm ed on an ultrasound due Lo p(]or vi-s-
i-t?iIiLy from Ihe vilneous haze ;K . ih e underwent a viLrec-
Lomv. scleral buckle, and Silicone oil p la cem e n t and her
relina has remained flat under the oil. She was continued
on systemic a c id o v ir tor 9 + months^ and игнI nind lopical
sluroids lapered over 7-й months. The oplic nerve remained
pale with narrowed retinal vase ltI a lure. H e r vision stabilized
at 20/2U0.
immune complexes.'Ji* Central vision, however, may be
retained in those patients who do not develop retina]
detachment because of the tendency for (he retinitis and
choroiditis lo spare the posterior pole (figure SO.44, Л-Е).
Approximately two-thirds o f patients with the acute ret­
inal necrosis syndrome are men. 'the second eye becomes
involved in approximately one-third of patients, usually
within ё weeks o f onset In the first eye. Involvement of the
second eye may be delayed for as long as 19 years. 1
In patients receiving early treatment with aciclovir, the
likelihood o f involvement of the fellow eye is reduced. 41
Most patients have no antecedent systemic disease. 1Eerpes
zoster ophthalmicus, the Ramsay Hunt syndrome, and
chicken pox may occur in some patients shorLly before the
onset o f acute retinal necrosis/" '1vn--r° 1 ' ' ■ 1|-715 ] herpes
simplex virus, aphthous ulcers, and EV cocaine have been
implicated in the development o f acute retinal necrosis in
severaEpatienis.70i-''11■
7lT-'
 FI Islopatbologic examination of ihe eyes of immuno­
competent patienls with the early slags of acute retinal
necrosis caused by lhe MZV reveals two ma[or compo­
nents: (1) sharply defined zones of ful E-thickness nec-
rolizing retinitis associated with replicating herpes virus
( I S;:;iv !0.4i4; and |2] occlusive vasculitis alfeclmg (he
choroidal and retinal vessels un associated wilh evidence
of replicating virus Within the blood vessels (Figure 10.46..
B], U5-f2i-73t Lhe thickened necrotic retina involving alE lay­
ers seen hislopal biologically corresponds with the zones
of dense retinal whitening seen clinically (Figure 10.44..
C, D, and G). In the areas adjacent lo the necrotic retina
where the retina is partly preserved, numerous intra­
nuclear inclusion bodies typical of the herpesviruses are
evident by light and electron microscopy in the retina
and RPE (I'igure 10.46,. G and IE). Immunocytopathologic
staining techniques, immunofluorescence, and PC E tech­
niques haw been used to identify the virus as herpes
zoster.67* ' In areas where the white necrotiz­
ing retinilis has faded from view clinically, only skeletal
remains of partly thrombosed major retinal vessels may
be found (Figure I0.46r G), Itte major retinal arteries may
be occluded as a resulL of infiltration of the arterial walls
by acute and chronic inflammatory cells as well as lipid-
Eaden macrophages (i'igure 10.46., 11). The choroid may
he focally and diffusely thickened by acute and chronic
inflammatory cells and occlusive vasculitis that involves
both the choroidal arteries and the choriocapiHaris {Eigure
10.46, C, D, and F). This vasculitis may be associated with
necrosis of the overlying pigment epithelium and outer
retina (Figure 10.46, F). A necrotizing optic neuritis may
he found [E'igure 10.46, F). No virus has been identified
in the uveal tract or in the Walls of the retinal vessels. It
is probable that Lhe H ZV does not invade the retinal and
choroidal blood vessels bul instead induces an acute reac­
tive inflammatory granulomatous response within the ret­
inal arterial wall, as well as in the choroid at vasculature,
that plays an important rule in the ischemic damage to the
timer and outer retina apart from the necrosis inflicted by
direct intrarelinal spread bf the replicating virus, '['his reac­
tive immune-induced vasculitis is probably largely respon­
sible for the panuveitis and necrotizing optic neuropathy
accompanying this disorder [E-'igure 10.46,. E).
l he same explanation may be invoked for the giant cell
arteritis associated with ischemic optic neuropathy {E'igure
10.43, F-l.) and contralateraE hemiplegia lhal occurs in
some palients with herpes zoster ophthalmicus.4^ '™ * '"11
Clinically the marked choroidal involvement (Figure
10,45 Continued
Varicella-zoster scleriiis and acute retinal necrosis
(AKN),
M Id R: This 6fi-year-old man wan seen eEsewhere and
Ire-лted with era! and topical steroids lor 2 weeks with a
diagnosis Ы panuveilis. He was luund to have sclerilis w ilh
severe pain and redness; in Ibe temporal qu.idrLtnl o f his rigtil
eye. Л choroidal detachment was seen under Lhe scleritib
Eilon^ w ilh s ij^n i fi слп1 viIritis and urLeriolar plaques iM - O i. A
diagnosis uJ A K N with scEer.il is secondary to Varifcella-zosler
virus was made. EHe received ora: vjiI лс icluvi г iVallrejtf, 1 g
three times, a day, nnd -tflh later oral steroids were added.
Two weeks later Ihere vi'at- some heaJing o f I he relinitis (h*:,
but be subsequently developed л rhe$$malo$encius relinal
delachm cnl in Che inlurio: and nasal t| lt jdram s IQ nnd 1^ .
He underwent л vitrectom y and repair ot [be retinal detach­
ment w ilh placem ent of -silicene oil . His relina has fem ained
altached though the arterioles showed occlusion wiLb several
periarCeriolar plaques.
10.46, Л. G. □. and F) in patients with acute retinal necro­
sis is largely occult because of lhe loss of transparency of
the overlying ischemic retina. On histopathologic exami­
nation of two eyes enucleated many months after partial
resolution of acute retinal necrosis caused by ll/.X. the
author found a smoldering retinochoroiditis and a glant-
cell reaction in the vicinity of bruch's membrane and the
internal limiting membrane of the retina/1 'I’his gran­
ulomatous response lo these collagenous membranes is
similar to lhal which may occur around Descemefs mem­
brane in palients after FlZV keratitis. 11 1J
Although most cases of acute retinal necrosis are prob­
ably caused by lhe herpes zoster virus, the herpes sim­
plex virus, cytomegalovirus, Epstein-Barr virus, and
loxjpku 1ГШ have been incriminated in a few cases/? ■
FsLablishing the cause of acute relinal necrosis has been
aided by recent success with PCR. [deviously, serial deter­
mination of serum and intraocular fluid 1EZV antibody
ievels, viral culture,, and immunocytopathologic tech­
niques were used to identify HZV infection in tissue sec-
^p(js.6ia731 : Biopsy of the retina at the junction of
the necrotic and unaffected retina during pars plana vitnec-
lomy is occasionally used for diagnosis.1n,-T i:: Our failure
lo recognize the acute retinal necrosis (ЛГСМ) syndrome
some 10 years ago suggests thal a mutation in Lhe FlZV
may have occurred, lhe genotypes EII.A-DQw7A and E1LA-
Jl\V 6 2 4 )FM occur in 5 5 % and 1 6 % , respectively (controls
19% and 3%), of patients with AKN.
 Although the necrotizing ret ini tIs Lypically appears ini-
Lially in the peripheral fundus, il may begin as multifocal
lesions in Lhe macula. Whereas progression of the disease
is usually rapid, in some cases a slow progression may
simulate that seen in other diseases such as toxoplasmosis
or reticulum cell sarcoma. During the acute stages of lhe
disease the differential diagnosis includes: (1) cytomegalic
inclusion disease, which almost always occurs in im mu no­
suppressed individuals, is typically less widespread, pro­
gresses at a slower rate, and is usually associated with
more retinal hemorrhage and less evidence of retinal arte­
rial occlusion; [2) primary herpes simples retinitis, usually
seen in in fail Ls hut occasionally in adults with encepbali-
tls;5^ [3} bacterial or fungal retinitis; {4) large-cell non-
llodgkin''s lymphoma [reticulum cell sarcoma), usually
in elderly patients; (5} diffuse toxoplasmosis, usually in
patients receiving long-lerm corticosteroid therapy or oth­
erwise im mu nosup pressed; (6) beh^et's disease; [7) sar­
coidosis; (3) centra] retinal artery occlusion in association
wilh severe carotid artery disease [ocular ischemic syn­
drome); [9J retinal necrosis in ^-linked lymp ho prolifera­
tive disease;750 (10) acute multifocal hemorrhagic retinal
vasculopathy;''' and [ l i ] human T-lympholropic virus
type ] (31'ILV-]) associated uveitis and relinal vasculitis.' J‘
Ophthalmoscopic pictures identical lo acute retinal necro­
sis have been reported in immunosuppressed patienls
with Hodgkin's disease,753 CN5 toxoplasmosis/^ cyto­
megalic inclusion disease/1 ' Kehcel's disease, " a n d giar­
diasis.' " I n some of these cases the acute retinal necrosis
may in fact have been caused by herpes zoster.
During the healed stage of acute retinal necrosis, the
pigmentary changes, chorioretinal alrophyr severe vas­
cular narrowing and sheathing, and optic atrophy simu­
late those seen in ophthalmic artery occlusion, Behcet's
disease, severe diffuse unilateral subacute neurorelinitis,
severe atypical retinitis pigmentosa, and post traumatic
chorioretinal scarring.
The diagnosis of acute relinal necrosis is based primar­
ily on the clinical picture and lhe exclusion of other causes
of relinal whitening and retinal vascular occlusion, '['here
are no consistent laboratory findings of diagnostic impor­
tance. Vitreous specimens are unlikely lo show evidence of
intranuclear inclusions, and although viral cultures may be
negative, [\; k is more likely to be positive. Relinal biop­
sies in this disease have a significant chance of missing the
limited areas where the diagnostic inclusions are present
in viable but inflamed retinas. A biopsy specimen should
10.46 Light and electron microscopic findings in the
acute retinal necrosis syndrome caused by herpes
zoster^
A Id И : ThromlHjtic u t d us-ive retinal arLeriLis of the Optic
nerve head (А and E3i. Ncrie vacuolated cells, either lipid­
laden endolhelial cdlh «г т л е ropha^es u m n v i. m Lhe w all
[)E 1h i у (icdud-od reLinai arLtsjy.
Kalina nasal [о [he oplic disc showing thf о т hosed relinal
arlery and marked necrosis c f the felina 1C.
ThromboLic occlusion o f [he cboriocapillaris and large
cjhcroidal artery undedvinj» necrctliL К PL ®S}.
Segmental in fare Linn and inflammation o f lhe nasal halt of
lhe rel rolam i na r optac nerve it..
Temporal r e L i n a shewing зЬатр ju n d io n of necrotiz­
ing relinilis and relatively normal retina. NoLe the eslensive
underlying choroiditis (F). The reLina in the m acular area (not
shown was well ргене!ved, and 1he dtoroidilis w a-к гтти ILi-
focal rather lhan diffuse.
Temporal relina show ing eosinophilic intranuclear viral
indusions wilhin retinal and bJI-’E cells G-.
ElecEron micrograph -showing intranuclear viral particles
in jeLinar cells (Hi.
1Л-С .in J F - H f m r r i ^ i i l I "ч r I“■i !11 L1! . i I . " - : L I . i r r d L f r o m j f j i d . -r , i
include the edge of a recently developed while area of reti­
nitis and its adjacent normal-appearing retina.
Aciclovir appears to be effective in the treatment of acute
retinal necrosis, and reduces (he risk of fellow eye involve­
ment. '[-^е treatment regimen for the acute stage
of acute relinal necrosis includes IV aeiclovir and, 2-3 days
laler. oral prednisone; these drugs are continued until all
signs of acute retinal necrosis have disappeared which may
be as long as b or more monlhs. Milder cases have been suc­
cessfully treated with oral valacietovir alone.' >l:-' Anterior
chamber cel Is tend to persisL for 6 months or longer, requir­
ing topical steroids. Resolution of the active reLinitis typi­
cally begins 5-7 day's after initiation of aciclovir. ' 1'realmenl
wilh aciclovir does not prevent relinal detachment only in
selected cases. E’rophylactic photocoagulalion Lo delimit
the zones of retinal necrosis may be effective in reducing
the risk of retinal detachmenL."""' 1: Approximately two-
lb irds of the patients respond well to scleral-buckling pro­
cedures, which may be supplemented wilh vitrectomy in
some c a s e s . Retinal and optic disc neovascularization
may occasionally occur and may respond favorably to pan­
photocoagulation. 6 there seems to be liltle rationale for
consideration of optic nerve shealh decompression in Lhe
treatment of ATCN optic neuropathy.'
A cu te Retinal N ecrosis in Im m une Incom peten t
Patients (Posterior O uter Retinal N ecro sis)
Immune incompetent patients, particularly those Wtth
AIDS, often develop a distinct cl in tea] picture of acute
retinal necrosis characterized by fewer inflammatory
signs* deep retina] opacification, frequent involvement of
the macula., lets involvement of ihe retinal and choroi­
dal blood vessels, poor response to antiviral agents, and
rapid progress ton lo severe biEateral visual Loss (l-'igure
I0i4^|b7fi3" '73 '['hough ihe fundus appearance appears
to be outer retinal involvement (posterior outer retina!
necrosis or PO RN syndrome), there is clinical and his­
topathologic evidence that the necrotizing viral retini­
tis also involves the inner retina early in these patients
(E-'igure 10.47, Л-Н and J-3*). ' Eiecause these patients are
immuno-suppressed, the acute reactive granulomatous
retina] ,md choroidal arteritis typically seen in immune
incompetent patients With HZV ARM is less severe, but the
replicating virus causes severe, rapidly progressing retinal
necrosis involving at] retinal layers. Progression to loss
of light perception occurs in two-thirds of patients. Early
aggressive treatment of the retinitis and Lbe immunocom­
promised stale u'ith 11AAR E is recommended to salvage
some vision. ■
ifl.47 Progressive outer r e tin a l necrosis (PO RN )
syndrome,
Л lo G : A cu le visual loss occurred ал fhi-s 4^-year-old man
who w a s H I V -p o silive. Note the m u ltifo c a l le sio n s sunound-
rny paracentral zones o f retinal whiLening that in vok ed the
inner a? w ell as 1he outer retina IA untl t3'. Angiography
showed evidence erf perifcKveoEar reLEnal vascular occlusion
and incomplulo staining of the w hile paracenlral lesions i£I
tu E!'. Two weelts laL-w be had severe visual lass and progres­
sio n o f llie nutiniLis <F?r an d 3 weeks aflcn th i o n set erf symp-
tunts be w a s virtually blind. Note the severe re tin al vascular
narrowing. optic d is c pallor, and BeJsiive sparing» d f the cho­
roid il:). The lefL eye was enucleated and herpes zoster viTLis-
li- IW i w fli tu I lured an d identified w ilh immunoliuoTescenl
staining w ith a monoclonal antibody (o varicella-zoster virus.
H to K: Visual loss occurred in this 39-year-old man w ilh
AI P i and a hislory of two episodes of herpes zoster der­
matitis. Note lhu multifocal whiLe relinal legions !H and Ik
1here was minimal vitreous inflammation, t in e w eek laler
his visual acuity was 2u£tOCl in tfiu right еуё and hand m ove­
ments o nly in Ihe left eye. Vision progressed rapidly Lo no
Eight perception in ihe right eye, w hich was enucleated for
dia^noslic purposes. H islopalholo^ic examination tf and K'-
revealed ox I enuave necros-is of the retina ibal m many areas
was more marked in the inner Ihan oulux relina. Note ihe
аЬнепсс Ы 'h e reLinaf and choroidal vascular inflamma­
tory response and compiare it with the severe inflammatory
re s p o n s e th a t o ccu rs in llie im m u n o c o m p e L e n t p a liu n l W itf ji
AКN caused by H Z V F ig u r e 10.46).
Ш.4. Continued

L h i;P: А 49-уейвУрвд African Am erica^ W a Irian com pi л itied

Й dw-T-eased vision irr IjcjIK ey^i; Khe was diagnosed w ilh
f IIW A ID b I monLh;; prior with л JCLJ4 count luui tii:нп 20. ih e
had -il hi story of C M V viremia, esophageal u.( еты. chronic
t;-asLritiыг hypertenaion, and oral candidiasis. H e r vision was
3/200 in the right eye and 2WflO En the left eye. EJoLh eyes
had widespread duop outer ruti-mil vvbjtejlfng in lhe m acula
and periphery with rEtinal hemorrhages ’.L. M and £>}. Ihure
were area* of relinal atrophy anlerior It- the peripheral at. live
lesions fOl. Angiogram showed late slain ing of lhe active
lesions and trailsrTiiiSFofi detticb of lhe alruphic zone's :N and
Pi. A uijfreOtfi hiopsv was piisalive for varkelJa-zoster virus by
FJCK and negative for C M V find H $ V i>hu -received 2400
[)t intravitreal foscamet in both eye;- and oral valgancrclo-
vir 900mg Iw ice a day. The w hilening disappeared and Lhe
lesions becam e pi^jmenled.

lA .Hid h ;riirn M.'ri'.ol;^ ^'1 . I (.i-l :rurn Mahgu' ; L-ll3^ (.outIcnj1

Ur UiLLiriLV ii-hih.l
HUMAN IM M UNODEFICIENCY
VIRUS (HIV) AND ACQUIRED
IMMUNE DEFICIENCY SYNDROME
Acquired immune deficiency syndrome [AIDS) first
became apparent In I У75 but has rapidly become л global
pandemic Jn the United Stales, the Centers for Disease
Control and Prevention (CD C) made lhe first announce­
ment of AIDS cases In five homosexual men in Las
Angeles who were hospitalized with R carinii pneumonia,
CM V infection and .candidiasis.780 The disease is transmit­
ted primarily by sexual contact that can be homosexual,
bisexual, or heterosexual; by parenteral transmission by
transfusion of infected blood products, or by injeclion
using blood-contaminated needles or syringes; and peri­
natally before, during, or after delivery.1' 14: J^s 7в-
1-а*3 '['he
definition of AIDS that was formerly based primarily on
Lhe acquisition of one or more 'indicator diseases' asso­
ciated wilh H JV infections, such as infection by opportu­
nistic organisms, lymphomas, and encephalopathy, now
Includes asymptomatic palients With СП4+ I'-lymphocyte
counts of less than 200 cells/pL^"
AIDS is caused by infection wilh the retrovirus human
Immunodeficiency virus (H IVJ, which causes a profound
Immunodeficiency resulting primarily from a progressive
quantitative and qualitative deficiency of the CD4+ sub­
set o fT lymphocytes referred to as the helper or inducer
T cells. ']Ъеге is an associated elevation of circulating
immune complexes and elevaled serum IgA and JgC lev­
els. The median time from H IV exposure to the develop­
ment of AIDS is approximately II years.''1' l]atienls often
are seen initially because of fever, generalised lympha-
denopalhy, a wide variety of severe opportunistic infec-
Lions. and, in approximately 30^4 of palients. the devel­
opment of a progressi4,e form of Kaposi's sarcoma. Ocular
findings occur in 50-70°/fr of palients. ЧЪе most com­
mon ocular finding is one or more cotlon-wool patches
[approximately 50- 70% of cases} (Hgure ID.4fir A),
retinal hemorrhages and Roth's spots (approximately
4 0 % J, microaneurysms (approximately 2 0 % ), and cylo-
mcg.ilic reliEiiLis i.ippmxim.iU'ly 2V',.'| f|-inures I' :-.T I ■
10.48, J3£.r)L7M'793'7?7 The cotton-wool patches are simi-
Ear to those occurring In other retinal vascular diseases
except that they are generally smaller in si/e."''' They
regress in 4-6 weeks. Iliey may appear early in the course
of the disease, and their appearance is unrelated lo spe­
cific infections or the general status of the palienl. When
these patches are viewed by fluorescein angiography, they
M 1.4 8 A c q u ire d im m u n e deficiency s y n d ro m e ,
A : C o l Lon-woo] spots.
!£ and f. : Photomicrographs of collon-wool patch. Note
c:yloi< I bodyr w hich is pari I у crucified (arrovw, Ur hwnnlosy-
Iin and eoSJ-n). Home of lhe calcificd 1issue (palfe ar&al wa$
dislodged during sectioning. The whofce cyloid ЬосГу stained
puj-ititeJy lor calcium i.C, von Kassa slaiiT).
D and E: Cytom egalic inclusion disease retinitis,
f-: Pholomicno^Tjph o f lhe retinni w ilh many cylom eyaljc
cells wilh. inLracylupla^rnic 'a rro w and irUfanudrar inclu­
sions - 'owl's eye' in a paLienL with C M V
relinilis.
G : Cytom egalic in clunion papiililis
H and L: C lin ical photograph (Hf and photomicrograph (h of
Kaposi's sarcoma of the inferior conjunctival cul-de-sac.
j: Kaposi's sarcoma ot" 1he.1 lower eyelid.
К and L: Kaposi "я нагсота o f die conjunctiva in a palienl
with А Ю 5 before (K) and several weeks after (L) subconjunc­
tival injection o f 0.5m L o f 3 m illion units interferon a(fa-2a.
I Ы .i n J t ! frurn l.in e n Jjju rn c l l-r сскгг1с:ьу U r N jri-in jj Нло: К .l ii H L
Г г а т Н и п и п е гч Д лЗ. ' 'I
are identical wilh cotton-wool patches seen from other
c a u s e s .JIIslopathologically, they are cyloid bodies asso­
ciated wilh arteriolar obstruction, basal laminar thicken­
ing. endothelial cell swelling, and degeneration of the
pericytes/^ We have observed calcification hislopalho-
logically within cytoid bodies in two patients with AIDS
(Mgure l0.4Sr В and Although structures resem­
bling Pneumocysib jirpuecH were identified In a colton-wool
patch in one case,"1there is minimal evidence to support
an infectious cause for the arteriolar obstruction. Vascular
damage from a circulating immune complex deposition
has been suggested as the cause. ^ HIV-1 has been dem­
onstrated In lhe retina, conjunctiva, tears, iris, and cornea
of patients wilh AJDSJ™ft-7?s',flC18 Ihe role of this virus in
causing cotton-wool patches, microaneurysms and hem­
o r r h a g e s , n o n s l a i n i n g eysloid macular edema.
macuEar star, optic neuropathy, or otherwise unexplained
visual loss in some palients wilh AIDS/'- iint|
in potentiating the effects of opportunistic infections Is
uncertain.'117
Most opportunistic infections occur in palients wilh a
СВЙ4- T-lymphocyte counl of less than 200 cells/p L Kor
opportunistic infections associated wilh AIDS, see the
following: bacleria, p. SOS; cytomegalovirus, p. -Й92; her­
pes zoster virus and acule retinal necrosis, pp. 900-910;
mycobacterium, pp. 830-й36; cal-scralch disease, pp.
S12-814; cryptococcosis, p. £42; histoplasmosis, p. Й46:
PneunKitjstijr, p. 85fl
 Cytomegalic retinitis and oplic neuritis are the most
serious ocular complications of AEL>S from ihe visual as
well as the overall prognostic standpoint (figure ]QA\,
A-L and P-T), Cytomegalic retinitis develops late in (he
course of ihe disease, is progressiver andr before ihe use
of antiviral agettls, was usually followed several weeks
after its discovery hy death caused by systemic infection
With CMV or one or more of the following: ftarumocyfiis
oirjpuf (jjftetssci) pneumonia, CrypUx&txiii neojonmun men-
ingiLis, Tnxopfcismrt gondii encephalitis,. and disseminated
Mycobacterium avium, Mycobacterium avium-inlmcdhilare,
and Candida With ihe intro­
duction of U,V\KT in the !ale l У90s, CMV retinitis can be
cured or controlled in some patients, though they may
haw to be on chronic ganciclovir treatment or receive
intravitreal ganciclovir im plaints. Immune recovery uveitis
wilh vitreous inflammation and cysloid macular edema
has emerged in ihe post I lAART era. where immune recon­
stitution elicits ail inflammatory response in patients
recovering from CMV retinitis. This uveitis can be treated
successfully with topical or local steroids.
Kaposi's sarcoma appears as one or more erythema­
tous violaceous masses that may involve the conjunc­
tiva.. skin of the lids, and occasionally the orbits [i'igure
10.43., ]Progressive involvement of the skim
mucous membranes, internal organs, and lymph nodes
may be the major cause of death in approximately У^/Ь of
patients. Hurkilt's lymphoma of the orbit and a variety
of neuro-ophthalmologic complications, usually caused
hy intracranial infections, may occur."u Intraocular lym­
phoma, squamous cel! carcinoma of the conjunctiva, ocular
surface disease such as microsporid ia keratitis, molluscum
contagio&um, and drug-induced uveitis (cidofovir and rifab­
utin) are other ocular manifestations seen in AIDS.
Therapy in patients with AIDS is directed toward inhi­
bition of replication of H lV by anli retroviral medications
I 0 .49 Epstei n-Ear r virus (ЕВ V ).
A to E: A 2b-year-«ld wom an dtvejljf^ped sudden fervor, dif­
fuse myalgia, ыоте throat. and <fiificu.1 ty iwa-mgwing. ie v e n
weeks- later shiti noted ocular discomfort, ГаНцие, headact|tf;
tinniLus, n i:!cl hearing, loss, and pericent гаI so&triiwL .Vlild
lympadenupathy nnd p^sftlvit^ phttrvn^ilis was found tin
examination. Retinal veins in both eyes had patchy phlebitis
iA - C Lh-nL on angiojjjaphv sJitjwied leakage from ihe venous
w all ID —C ). All laboratory t-esLs w ere negative except for pos­
itive lj=M and Ij^C antlEtodjeH lo ttSV and л quantitative fc№V
FCb? was positive in 500 copies/mL. The lesions responded
to oral prednisone a I бОтэд tw ice a day I hat was tapered a I
2 0 mg per Wtelc v\ ith com plete resolution of the phlebitis; in
both eyes i.H and Г.
] L(] N : Л ЬЗ-уидг-cild wom an with palholofjpc myopia and
a cenLral scar in I be left macula noted a Tapid decrease in
vision in her yood right eye. 5he developed headache, neck
siliifness, malaise, and cervical adenopathy- W h e n examined
a week later, ih e righl eye showed fa in I yello w Земопк in Ihe
macula, and Lhe lelt was unchanged w ilh a pre-exisling atro­
phic scar (Jf. Nineteen days laler her vision in the rijjhl eye
and control of opportunistic infections. Chemotherapy,
cryotherapy, local excision, and tumor infection with
alpha-interferon are used lo control Kaposi's sarcoma
(Kigure 10.4S. К and L }.™
Although 1LEV and AIDS initially were diseases of the
developed countries and Africa, the incidence has risen
dramatically in olher parts of the world, with the largest
rise occurring in South East Asia and India. 11IV transmis­
sion in these countries is mostly heterosexual. By 2007, an
estimated 33.2 million people worldwide and I million in
the United States were i IIV infected. Women and minori­
ties have shown a rise in incidence, along with men who
have sex wilh men (M SM ) who continue lo be a high-risk
EPSTEIN-BARR VIRUS
Epstein-Barr virus (EBV) infects virtually everyone by
adulthood, nind a lifelong latency is maintained. Et infects
children silently, whereas the majority of adolescents
develop infectious mononucleosis (EM}. Thus the conical
outcome of EBV infection is aye dependent. Children with
primary immune insufficiency can have fatal or chronic
1M malignant IJ-cell lymphoma, virus-associated hemo-
phagocytic syndrome, aplastic anemia. or acquired hypo
gammaglobulinemia. Part of the predilection for AiDS
and other immunosuppressed patients to develop ft-cell
Lymphomas may result from EBV infection. Aciclovir and
immunoglobulin therapy can be of value in some patients
with active EBV ^ fe cd o ^ *14^ 5 Ocular involvement sel­
dom occurs in patients with other clinical manifestations
of EBV. A variety of ocular disorders associated with EB\f
infection have been reported, including acute necrotizing
retinitisJl:','<
’'?i2li ouier punctate retinitis si mu Ealing toxoplas­
mosis,' ■1 multifocal choroiditis and panuveitis (Figure
10.4 9, J-L* and N[)r730,ja27 anterior uveitis, severe panuveitis
with optic disc swelling. macular edema,11''' and possibly
retina] phlebitis [Figure ]0.49, A-]). There is conilicling
information concerning the incidence of serologic evi­
dence of recent EBV infection in patients with multifocal
choroiditis and panuveitis (see multifocal choroiditis and
panuveitis- p. У88).
HUMAN T-LYMPHOTROPIC VIRUS
TYPE 1_____________________________
I Luman T-lympbotropic virus type 1 [HLTV-1] es a human
retrovirus that causes adulL T-cell leukemia and lymphoma
and HI'LV-1-associated myelopathy (H AM ).
The virus is endemic in the Caribbean, Etaly, Middle
East, subTSahiran Africar and southwest Japan includ­
ing Kyushu and Okinawa i5laпds.:,'>,'■н■,J■::',l A small
number of these patients develop adult T-cell leukemia/
lymphoma myelopathy. The remaining carriers may
10.49 Continued
was- 2Q/20Q and the left was couni linden?.. Пите? were я tow
vitreous colts bilaterally and c<*aele£cin£ yellow lesions were
nulud in bolh m;icula wilh Litt.1 sipaiinfj of Ihe peripheral
rrlina Hind blood Vessels -.K and L:. Laboratory Lotting shcAv^d
lymphocYtabtS huL negative for syphilis. Lymti disease.. -and
Toxopiasma. She underwent a vitrectomy far a concern for
lymphoma which showed atyijrcal lymphocytes ch-iirHcterii;-
lic oi fctiV infection. She Was sLafted on vfllaciclovir 1 ^
three limes й day and oral prednisone 50mj^ per day. O ver
the next 2 weeks her inflammation subsided, (lie lesions
LLirned alnuphic IN I and the yiSfcwi slnbiliiied aL J2Q/B0 on the
ri ^.ti I a nd с ou п I l ingers on 1be lefl.
|{jjurCtsy: Л-Ё LJr V'lic.h.H'l Ak.iwrul: J--V Ur ^luphL'ii K.ni.inJLJr Daniel
M e r li n . R e p r in t e d v r i lh jj'L T jn is :;L in I ru m R i ' l i n i t C d s e i ;tn d H n c l b . p d l t L .
remain asymptomatic and otherwise healthy or develop
uveitis or retinal vasculitis.'ej4' Eii'' The uveitis can be granu­
lomatous (75% ] or nongranulomatous (25% ). It es usu­
ally a panuveitis with white retinal lesions, viireous cells,
fluorescein leakage from the retinal vessels, and vari­
able anterior segment involvement It can have a waxing
and waning course, usually responds to steroids, and can
n n i L ^ ^ ^ W 41 A small subset of patients with E-TLTV-f
antibodies develop a recalcitrant retinal vasculitis and pro­
gressive chorioretinal degeneration, i'his disease does not
respond to steroids and appears to be at the severe end of
the spectrum.' '■ Some of these patients may eventually
develop myelopathy, lhe clinical appearance resembles
C U V retinitis, acute retinal necrosis, and frosted branch
angiitis, but does not respond to ganciclovir. Vitreous and
retinal biopsy with 1JCR identification of HTLV may be the
ouiy way to establish a diagnosis in nonendemic areas
Adult T-eell leukemia [AE'Lj patients can develop a
picture of retina] vasculitis and in fill rates confirmed by
biopsy showing infiltration of leukemic/lymphoma cells
in the retina. These patients are not necessar­
ily from the endemic areas {see Chapter 13, Hg. 13. 33).
intraocular lymphoma with yellow-white sub-RPE depos­
its has also been very rarefy caused by iTITV-1Л1'1H" '
/^jjijji]jj T-LifmjdtojtTvplc L type J 91 7
RUBELLA RETINITIS
Children born of mothers who contracfed rubella dur­
ing the first trimester of pregnancy may show a variety of
anomalies of development of the eyes and other organs
(E'igure Ю.50).и'16-(д,и In these children there is a high
incidence of What has been described as sait-and-pepper
mottling of the RPE (FJgmre 10.50, Jhis is
often most prominent in the posterior fundus. Both eyes
are affected In БО^Ъ of cases.'’ '' Early progression of the
pigment mottling in childhood may be caused by persis­
tence of the rubella virus within the ИГЕ. Pigment mot­
tling, however, becomes less prominent in adulthood.
]"his. pigmentary change of the fundus may be accom­
panied by evidence of pigment loss from the pigment
epithelium of the irides, which in some cases will transil-
Euminate in an irregular fashion [i igure 10.5О, C j. Lhese
alterations of the RE4. may occur alone or may be associ­
ated wiLh other ocular abnormalities, such as cataracts
and microphthalmos, and systemic abnormalities., includ­
ing deafness and congenital heart disease [Figure 10.50,
A and Bj. in patients with evidence of RPE involvement
only, the visun^l acuity is usually normal. Choroidal neo­
vascularization and disciform macular detachment may be
a late complication of rubella retinopathy (Figure 10.50..
-,Ъе electroreti nographic nnd
electro-oculographic findings, color vision, and visual
fields in most patients are normal. lluorescein angiogra­
phy shows mottled hyperfluorescence caused by extensive
and irregular loss of pigment from the 1111!: (figure Ю.50,
II and I] and may be helpful in detecting early choroidal
neovascularization (Figure 10.50. U). Aulofluorescence
imaging shows finely mottled decreased autoiluorescence
10.50 Congenital rubella.
A: This child JihcI microphthalmos and саМпэс! in ihe lefl
eve. rubella relinopathy in lhe- right eye, hearing Ujhk, donMl
hypoplasia,. and congonila] Ьедг! mbeasg..
В tci E: Dental bypaptssia ■В I. iris а1гигпд1 and R P t atrophy
and rubelEa retinopathy (D J in a 4-year-old boy whose
mol her had fuholla in 1h f firs! trimosler of pregnancy. Note
Lho extensive ф еГапйетйЛ Ы ifu1 hif’Ei :Dl. His visual acu ­
ity Was normal. Л1 Age 1 1 years, Ihe RF3!: changes wore less
apparent |Ё].
F Icj I: Ь!иЬе11д retiпордIhv :h and G ) in ,1 ^-year-old boy w h o
developed loss til visit]n in ihe rigbl eye secondary to sub-
fovcal cbom idiil neovascularization Unrow , F). Hi-s mother
received gammaglobulin injections during ihe First trimester
o! pregnancy Ьесд use of exposure to an epidem ic of rubella.
His visual acuity in the left eye w as 20/15. His electro-
oculographfc and eleclronetinographic findings w ere normal.
Angiti^jiiphv in ibe ri^hl gye showed evidence rjf choroidal
neovascularization (H i anti widespread alterations of the R P t
in ijolh eyes IH and tj.
) and K: tlompnre ihe prominent RPE: moLtling associated
with rubella in an I 1-year-olcl JJ witii that of ihe т о т е subtle
mottElng in a 37-year-old man iKn. Angiography in the man
shows evid en ce of marked hypopigmenfation o f the RFE.
Visual ncuily was tjormal in bolh patients.
corresponding to the areas of KPL loss."'’01 Pathologically
the salt-and-pepper changes in the fundus are caused by
altered pigmentation and some atrophy of the RPE.^4,
1Ъе retina and choroid are unaffecLed. Rubella retinopa­
thy may be mimicked by inherited dystrophies of the
Rl’ti, (see Figure 4.05J, the carrier state of X-Einked ocu­
lar albinism [see Figure 5.37, |). X-l inked choroideremia
{see Figure 5.2S., E-, and F), and toxic diseases of the RPE
(see Figure 9.03, А-К}.'414'
SUBACUTE SCLEROSING
PANENCEPHALITIS
Subacute sclerosing panencephalitis (Dawson's encepha­
litis) is л progressive neurologic disease representing a
slow viral disease caused by a defective measles virus. It
typically follows a preceding measles infection in children
and young adults by a mean interval of 7 years. Males are
affected three limes as often as females. Personality and
behavioral changes are usually followed by dementi a,
seizures, myoclonus, and death. It occasionally occurs in
young adults, who may recover with only minimal neuro­
logic deficit {Figure 10.51, C-J}. Ibe disease can occasion­
ally be seen in adults above age 25 and has been reported
Ёп a 49-year-old raan,s® Kiflv percent of patients will have
involvement of the visual system. Visual comp]aims often
antedate the onset of neurologic symptoms by several
weeks. Neurologic symptoms may be delayed as
Long as 12 months. ' - ^ost patients have л his­
tory of preceding measles [rubeola infection], usually
before 2 years of age.
The patients may he seen initially because of loss of
central vision caused by one or more small. fla^. focal,
white retinal lesions or larger, more ragged, gray-wbile
areas (Jigure Ю.51, A - p ]^ .. s<^ Hither one or both eyes
may be affected. When the retinitis Involves the center of
the macula, a cherry-red spot may be
Jhe white retinal lesions resolve rapidly and are replaced
by irregular areas of ЙРЕ atrophy, gliotic scarring of the
relinar radiating relinal folds, and occasionally retinal
hole formation (tigure ]0.5]r В and G-|). lhe pigment ary
changes may be misinterpreted as heretlo macular dystro­
phy. lbe pigmentary changes are not always confined to
tbe mSaaila^3*'871 '['here is minimal evidence of choroi­
dal involvemenl. Jbe vitreous is relatively free of inflam­
mation. The oplic disc may be swollen or atrophic.!4"b,i’--
Angiography Is helpful in delecting subtle changes in the
RPJv' J Other causes of visual decline cat] present as
ho mo пу mous he mia nopia or conical b Lind ness.e '
liislopatbologically, the acute stage of subacute scle­
rosing pan encephalitis is characterised by patchy focal
areas of retinal necrosis* pigmenl-laden macrophages,
minimal evidence of inflammation in the retina, loss of
pigment from the RPL, and minimal inflammation in
the choroid.:ч■■'■::'"l■
л"':',:i:,c, lл ter the retina may show focal
areas of atrophy of the inner, outer, or both layers, with
disruption and hyperplasia of the RPE and the presence
of tiowdiy type A and Cowdry type К intranuclear inclu­
sions as well as some inlracytoplasmie inclusions ( higutl
10.51, K) viral particles typical for measles virus
have been identified in both the retina and the brain of
these pattfeii|kSJJ-t,,1,a67,Jfi9 11 affecLs both the while and
gray matter of lhe brain. Evidence of measles virus has
been demonstrated in die relina utilising immunofluores-
cent techniques.^"'7'4rlhe demonstration of high levels of
10.s i Retinitis caused by suhacule sclerosing
panencephalitis.
A and 8 : Thrs 12-year-old boy had several patches o f acute
re lin k s in I he l i^liI m acula (A), H u had similar lesions rn his
loft BWfc l-tis visual acuity was 20/400 in IKc? rijjht eye and
finger counting at 4 lueL in Iht? Fell eye. NoLe the? cherry-red
spot. Ten dлуы laler I here was partial clearing of lhe cenlral
lesion and evidence of a larger lesion temporally :H\ A l lhal
Lime ho had no neurologic symptoms and the neurologic
evaluation was normal. During [he nesi month, however, he
became lethargic, mute, and bfind. H e died 2 months laler
ol cardiopulm onary arrest. H e had been exposed to measles
at age 5 and had received attenuated measles virus vaccine
5 months before Lhe onsel of visual symptoms.
С Lo I: A healthy 21-year-old man had a 1-week history of
blurred vision in his left eye. Al thaL lime there was evidence
of retinal whitening associated w ilh some hemtitThagp id),
lh e righl fundus was w ilhin normal limits u x c c jj I for the
presence ol A small hemorrhage in the macula. A medical
eva I ua I i on Lhat Included spinal fluid exam inal ion revealed
a rubeola IgG liter in Ihe cerebrospinal fluid of 1:64. w hich
was ihou^hl to he diagnosLk of suhacule sclerosing panon-
ctiphalilis. The pa Lien L's pasl medical hisL-ory was negative for
measles or immunisation against rubeola. Three years previ­
ously he had been hospiLalized for brain fever of uncertain
etiology Two wi'c-ks afler visual loss in lhe left eye he noted
loss of vision in Ihe righL eye. Ё ж а т Ё п т о п revealed an irreg­
ular area of necroLi^in^ ret ini Lis ll>'. A iluorescein angiogram
revealiH evidence oE perivascular leakage ol dye and some
slainin^ ol the lesions b .uid Pi. The reLinai lesions- in his left
eye had parLfy faded (G). An electroencephalogram revealed
findings com patible w ilh subacule sclerosing panttncepha-
litis. Six monlhs laLer Lhere was irregular scarTinO and thin­
ning ot Ihe reLina iit lh e m acular area ol both eyes ■'HE and Г.
Visual acu ily was counting Iinfers at 3 leet.
I and K: Irregular pigmentary disturbances ol the macula
and mild papilk'dem a caused by subacuLe sclerosing panen-
cuphalilis (j) jn an El-year-old l>oy w h o 4 weeks previously
became lethargic, incontinent, arid finally coma Lose. He
died 3 weeks laler, and histopathologic exam ination o f Lhe
m acular region revealed an atrophic ihinned relina conLain-
ing large masses of mu hi nucleated syncylial giarcL cclls con­
taining numerous intranuclear eosinof>hilic inclusions (Ю-
[A a n d tf fttxn L in d e ft .irid KlUhlwrjHti *.'• I9 7 E , A m u ric .m .VtucliciLl
Л ■
-■
:>l-:. 11:ijn А Ц rtjJ.hta t4.m rv«d ''J- l,'L iiu rlc ih IJ r _W. . i i ilIl■
г ’ n Ljn rd
and V in t; I , i n d К Гсгэтп 1-г>=--:
O r A jn d r e w K. 1
г : . 1.'" ^ <!i 1 ^ 7 ^ , A r n r : r i c . . i i i
M edbcal AsroLj.bl-Hjn. A ll n^hls Г4.^сг™(г. ■
measles antibody in (he serum and CIS К is helpful in estab­
lishing the diagnosis. The electroencephalogram shows
bursts of high-amplilude, sharply contoured, slow-wave
complexes. E'2-weigh ted lVi KJ shows diffuse or focal peri­
ventricular and subcortical white matter c h a n g e s .'lltere
is much evidence lhal subacule sclerosing pan encephalitis
is caused by an altered form of the measles virus. There is
no effecti4re treatment. High doses of intrathecal alpha-
and beta-interferon or via an Omega reservoir wilh oral
isoprinosine administered over 6 weeks has, however sub­
jectively improved symptoms, but has (ailed to prevent
death.
 The acule binge is most likely to be confuted With toxo­
plasmosis, CM V infection, Rift Vajley fever retinitis, acule
posterior multifocaj placoid pigment epitheliopalhy, or
one of the sphingolipidoses. the I ater pigme tiled stage
of the disease is most likely I d be confused wiLh Vogl-
ipielmeyer disease (neuronal ceroid I:ipofusci no&e-.s: see
p. 4 IS ) or Stargardt's disease.
Subacule sclerosing panencephalitis may be precipi­
tated during cytotoxic and immunosuppressive trenitmen t
or in immunodeficiency states, which lower the resistance
of the host to the measles vims.1"” "'*'
10.52 West Nrte virus relinitis.
А to C: An fiO-veai-old man with nonprolifera.trve diabetic
relinopaLhy cropped his left eye vision lo 2tV4(>0 й о т
2 0 4 0 . !n add iLi on to Ihe scattered microaneurysms.. dot and
Mol h#monti£jdes and lipid, there w ere ring-shuped tbo-
; i[jrt.4iiTal lesions .interior Eo the macula fA and E3:. lie also
developed malaise, muscle weakness, dysarthria, confusion,
and jjiiKlToonlerins tonsislenl vvilh a diagnosis of Wt'M h №
virus encephalitis. The anyioyram shows the circular legions
in addition to Jen king microaneurysms and m krovascular
abnormalizes (O-
D (о I: A 57-year-old Caucasian wom an developed sevefe
headache, lover, and was 'Loo sick Eo move' w hile caring

WEST NILE VIRUS fof her mother With a vira iliness. 4 it; was on a^athioprme
(Inmranl 5Grng once daily and prednisone 5 my o n ce dally
CHORIORETINITIS________________ for myaslhenia gravis EhaE was in remission. She developed
pafalysis and hearing loss in Ihe inlensive сапе и nil. A t she
Ihe West Nile virus [WNV) is a single-stranded НМЛ virus bei^an to recover Irom die paralysis and I be hearing loss, she
Lhat belongs to the Japanese encephalitis virus group first noled blurred L'onlral vision in Ihe left eye. ^holographs vvefe
isolated in 1337 in the West Nile district of Uganda. 'Jlie taken b weeks from ini Li a I pjresenEaLion w hen her visual acu ­
first documented case in New York was in 1995 after an ity W as 2Q/3P on Ihe righl and 2(W250 on Ihe let"(. CJomposiLe
photographs of the right and leN eyes show ring-shaped
outbreak in birds. Outbreaks of West Nile virus encepha­
chorioretinal scars d iь-triIз-иled lhroughoi.il Ihe fundus., some
litis occurred between 2002 and 2003 in ihe United States
of them arranged in a row lartfitv :tJ and E). The an^ioj’ram
and several cases o f chorioretinitis and panuveitis were depicts Ihe ring lesions belter, vvilh evidence of oct lusivu ret­
reporled.s' ■ Outbreaks also occurred in other parts of inal vasuulilis in the left macula th-ll.
the world including Ги^ЫаЛ*1-^ 4 I'he infection is trans­ ItJu U h C rtJ1: A - L . k;.'ii A iJn Im .L ii; ]>~J. U r M i l I i ;-i <.I J l ih iij l t .
mitted by ihe bite of a Cute.т mosquilo. which acquires the
virus hy feeding on infected birds, and has an incubalion
period of 3-14 days. Only 20% of infected individuals
become symptomatic and approxiEnately 1 in 150 infec­
tions result in encephalitis or meningitis. Sudden onset of
a high feverr malaise, myalgia, nausea, vomiting, arthral­
gia, and a maculopapular rash are symptoms of ihe sys­
temic illness.
Ocular involvement is characterized by mul.tifocalr ring­
shaped, yellow-1 white chorioreLinitis With the lesions oflen
arranged in a linear (Figure 10.32, A-F) or scattered pat­
tern. Nongranulomatous anterior uveitis, optic neuritis,
and reLinal vasculitis (Figure JO.52, G and Elj occur in
some eyes/’7' There is a higher incidence in women,
in diabetics (figure 10.32, A-C), and those of older age.
Treatment consists of topical steroids lo control inflamma­
tion. ihe lesions evenluallv heal with pigmentation of ihe
edges. Most eyes show improvemenl in vision unless ihe
Lesion involves the fovea I center or develops lale choroidal
neovascu Larina tion.
laboratory con firm alio n is by demonstrating IgM anti­
bodies specific to W N V during ihe systemic illness or
encephalitis.
©
DENGUE FEVER
Dengue feveT is a viral illness endemic in tropical Hind
subtropical regions... including ihe Caribbean,. South and
Central America, Asia, Africa, and the E’acific. L'he female
Aides aegypltifalbtfpictus mosquito transmits the disease,
hive clinical syndromes can occur: nonspecific febrile
illness classic dengue, dengue hemorrhagic fever, den­
gue shock syndrome, and unusual syndromes such as
encephalopathy and hepatitis. Classic dengue presents
wilh an abrupt onset of feverr severe headache, myalgias,
arthralgias, nausea, vomiting, and a maculopapular rash,
ihe rash eventually becomes confluent, sparing small
islands of skin. Dengue hemorrhagic fever affects children
less than 15 years of age in hyperendemic regions with
increased capillary permeability and hemostatic distur­
bances as its hallmark. Ihe most severe form [grade 4J is
associated with profound shock and circulator- problems
and is termed dengue shock syndrome. I hromborytopenia
causes petechial bleeding, epistaxis.. and bleeding gums.,
and can manifest in the eye as retinal hemorrhages and
! (j.j 3 De ngue re Сiлорд Ihy.
A lo F: Bilateral disc edema, perivascular infiltrates,, and
nelinal hem onhages associated w ilh mild ank^rior uveilit in
a 33-year-old Chinese wom an in Singapore, b days after the
□nfflt of dengue lever (flj Lind И). Her E>eHt corrected visual
Eicuitv was 2(У4СЮ in each eye. Early knobby hyperflunres-
Cencti; Dtlhe y e n jla r w a ll in the posterior pole? anti elHewbwe
(amnvs) in both eyesr w ilh Eale leakage was seen (C-F).
G lo L: В ilateral retinal white dots in fhte m acula in a
16-ycar-old girl w ilh visual symptoms 7 days after lever
onset. H e r visual acuily was 2CV4D in the right eye and 20/50
in ihe left eye. The w hite dais лги hypcrfluorescent (m the
I -uorescein angionram and hypoHuor^bcfeil on mdncin'anino
ib g io g ^ b h y 11CIt j i arid remain -so in the late phase. IC ti
shews more dots thiin sucn on the angiogram.
loss of vision."111 Macular hemorrhage, retinal edema.,
optic neuritis, ischemic optic neuropathy decreased axo-
plasmtc flow, macular exudates, and retinal pigment
epithelial Eesions are seen. E'actors contributing Id the cir­
culatory1 disturbances can also cause choroidal effusions
and second ary serous retinal detach ments.'"'
 Ocular involvement occurs in a small subseL of palienls
and manifests I week; after fever onset. Ih ey prebent with
retinitis, arteritis and relinal hemorrhages, with of With­
ou L associated anterior uveilis and vitritis. Cotton-Wool
spots, retinal hemorrhages, and branch relinal artery
occlusions are common findings [Ngure 10.53. A, Efj. M,
N, and []] "lu" Fluorescein angiography reveals leak­
age of dye from arteries and veins and evidence of aneri-
olar or venous obstruction (figure J0.53r C-t] Or Q,. and
l?J. Indocyanine green angiography reveals additional
dark spots nol visible on the angiogram (Figure 10.53, К
and L). Thrombocytopenia lhal accompanies ihe infec­
tion is responsible for the retinal hemorrhages in those
eyes ivilhoul florid vasculitis. Anterior uveilts is non­
granulomatous. Although the fundus appearance can
mimic B e h c c f s disease, the temporal relation of the ocu-
Ear involvemenl Lo the systemic manifestations of dengue
fever differentiates the iwo conditions. Stellate neuroreti­
nitis- foveolitis, optic neurit is, jnacular edema, exudative
retinal detach men l, and macular infarction have all been
noted
1GF53 Continued
M lo O : ierctuh т;н и 1 аг detachm ent nerve JiEier mfartls
and few w hile dols in the ri^hl eye of rHi-E 27-уйЙгаш (M>.
Angiogram hhtms involvement of lh-е vessel w all and non-
регГимоп (jf Ihe? retinal capillaries cnrrespbjridEng to ihe nerve
fiber i m t d (O ).
P to S: A 21-year-old Indian female complainEKf of vision
loss in her M L eye 7 days after Ihe onset oF lever,, d i n itafly
suspected to be secondary Lo dengue. Her visual I acuily was
20‘''400. ih e h.id Iw o patches o f rtiliiTiLia w ilh reLinal ppacif)-
cation, h^morrh |Bgesr iir|d 3ipicl thtMafes <P). Ihe angiogram
revealed assoc in led nflChjangmie with Nile leakage of dye (EJ
and K.1. O ne month taler her vision hjad improved to 2CV100
w ilh resdjulfeffi of ihe reLinilis .1I'd i4‘s it3u.il lipid ex и dales
anti relinal hemorrhage (Sj_
'■ ir ■ ■ ■
t_qj(jrle iy : A —Q , L Jr Kocn-I’h.nk С bee, reprin ted Irtun M.ics.il c l dt.
J|j|)7 r Лтс.'ги.лп MimJi i ■I AxwcffcUtm ЛИ г jH jtl ptSt^rerl, I 1-S. LJr
V llh ili G u fA v j
CHIKUNGUNYA VIRUS
An ou Lbгедк of chikun^unya occurred after 20 ye its since
the previous episode in India and some is]a [ids of die
Indian Ocean in 20(Ж Л14Л'‘' ' Chikungunya fever was first
described in 1955 after an outbreak on ihe Makonde
Hateau along the border between Mozambique and
'ijnzania. Ibere have been subsequent outbreaks in India,
Vietnam, Indonesia. Bangkok, and Myanmar. The vims is a
single-stranded RNA virus of the genus Alpiumnts, causing
fever, headache, fatigue, nausea, vo mi Ling, myalgia, rash,
and joint pain.
Several reports front the Indian outbreak of 2006 have
described ihe ocular manifestations which include con­
junct vitisr unilateral or bilateral iridocyclitis, secondary
glaucoma. retinitisr vilritis. retinal hemorrhages, neuro­
retinitis, and optic neuritis.' ша l:ocal areas of retinal
whitening with adjacent retinal hemorrhages characterized
the retinitis (figure JO..154, A-l:). An angiogram revealed
vascular occlusion and leakage with hte staining of the
involved, retina [t-'igure Ю.54, ti, II, and 1) and serous reti­
nal detachment (l:igure 10.34, \ and K). Ihe ocular signs
appeared approximately 3-4 weeks after the onset of (he
viral illness; hence it may he an immune-mediated rather
than a direcL viral infection. However, these mechanisms
are not well understood given the rarity of the disease.
Treatment is mostly supportive. Some patients received
oral/iV aciclovir and systemic steroids, but whether this
modified the ciinica! course is debatable. Jhe visual recov­
ery was moderate, with complete resolution of the con­
junctivitis and uveitis. Those patients with optic neuritis
had a less than favorable visual outcome.
MUMPS NEURORETINITIS_________
Papillitis and neuroretinitiSv usually associated with clini­
cal evidence of meningoencephalitis, occasional!y develop
in patients With m um ps."^"'1 One or more foci of retinitis
may also be present. Most patients recover normal visual
function.
1(3.54 Chikim gun уa retlni Lis.
A lo D : A 4fl-year-oid Indian man presented with gradual
rliminLilioi~i Ip vision in both eyes inr L!> data, i months after
a bouL of pnulonj'cd lover. H it vJs.uaI acuity was 8/200 in ihe
rigtil uye and couni fingers at 3 Feet in Lhe LefL eye. Anterior
ые?(^пи_ьгИ w as иптегтиаrkablс. Both lundi had relinal infanc-
Lacjn and bemqfrKagfSS in ihe macula Hind a.mnj r*d the disc iA
and B). Aqueous FCK for H W , VZV, and C M V w ere negative.
FiT-I^CK ffih t ' hiкиnguпул virus delocted nine copies o f viral
RN A 'm L. H e received (wal va Iaciclovir anti prednisone. Two
monLhs Irater his vision had im proved Lo 2 Ш )0 And 2(V80 in
the right and lefl eyes, respectively. The retinal w hilening and
hter^prrhages had imprcjved fjgt am i Di
E lo M : A 42-year-old Indian man complained ul biuired
vision in both eyes fur 2 weeks w hich began 2 weeks aller
a lever. His vision was 4/100 in each eye. There w ere fine
pigment specks on ihe com eal endothelium and flare in
both eves;. U-olh eyes had relinal whitening and hemor­
rhages and jnlraneCmal edema, and Ihe left iiad shallow
serous deLichm enl in- add Иion L and H. The optic: discs were
h yp erarik bilaterally. Angiogram showed hypoperfusldfl
in ihe early phase and Iale hyperfluorescencE and leakage
in Ivith eyes fG-l:. O CT of the right eye showed intrareLi-
nal edema and Ihe left intraretrnal and subretina I fluid ij
and К I. H it Chikunyojiya lg.Vl ап Ii body was posilive; den­
gue rapid lesL, tToponemal hemagglutination, HiiV-l and -2.
and Toxoplasma anybodies w ere negative. He received IV
aciclovir for T w eek followed by oral aciclovir for 8 weeks,
and 4 0 my of oral prednisone tapered ovbj b weeks. Ten
weeks after onset his vision returned lo 20/20 and Ih e retina
appeared almost normal in bolh eyes ■! and .Ml.
lA - JJ, ч L i u r h j v y LJ r I . L U v l v ,^; a i n d D r . S u L / h . u ^ h j i n . L—k.. c fiU r t a j
U r к 'v l.ih i.in J m l I lI S . г ■' i 1i i I -1<■■I f n j m M a h r n d r jid a s e l л I . 1
RIFT VALLEY FEVER RETINITIS I f i. j ^ R i ft V a lle y f e v e r re tin it is.

A to D: This 40-year-ald Saudi wom an had a sudden loss

Щ Valley fever is an acute disease primarily affecting
cattle and sheep caused by a specific Arthropod-borne
virus thiil is endemic in the western one-third of Africa.
Epidemics involving humans have occurred, the most
severe of which caused the death of слгег 600 people in
T£ypt during 1977 and 397Б. In autumn of 1000 an out­
break occurred for the first time in Saudi Arabia {i'igure
10.55).'4' In humails this is typically an acute febrile
ill ness wilh biphasic temperature elevations mimick­
ing dengue fever, it is associated wilh muscle and joinl
pains, headaches, and occasionally nausea and vomiting.
Conjunctivitis and photophobia are common during lhe
early phases of the disease. Visual loss occurs often days
or weeks after .subsidence of lhe fever and is associated
o f vision 1 0 days after developing fever related lo Rift val­
ley fever -КУИ. Seftim I^M for HVF vifus was pusilive. Her
visual acuity was count fin^ere at 1 meter on I fie right and
2 0 / 2 0 on the lefL. She had 1 -I- anterior d ia rfa e r rind vilne-
ous tells. A cream y macula* lesion w ilh tw o r a a c e n l reLi-
nal hemorrhages Was seen (A). Tbe lesion scarred down u w r
time w ilh folds- in the sujroundin^ inner relina a I 2 years !Ё'.
The visual acuity remained aL count finders. Ал a.rgiq£f3ffi
showed staining o f (he fovea I scar and a linear w in d o w
defect exlendiny to № ed isc edf^e and &j.
E: A n o lh w palienl w ilh ureamy foil-thickness rtrtinitis involv­
ing the macula, associated with positive Liters tor RVK virus.
F and G : Two other patients 1-1 years alter presentation w ith
alnophic and parliv p-i^mented scar in :he macula.
I\ jju r i.i:- jy : [ J r A d A l- h i.i^ .t n t i r ^ p r i n l L i i J i l f t J W i A I - I I.iL .- in ji l : .1 ■ ''I

wilh multiple areas of what appear to be acule necrotiz­

ing and hemorrhagic ret ini its in the maeuljr and para­
macular areas (Figure Ю.55, A and К), simitar to lhal seen
polyserositis, arthralgia, and impaired intesLinal absorp­
in subaeule sclerosing panencephalitis and the herpes
tion. Other features include mesenteric and peripheral
viruses."1""- Vitritis and occlusion of the major retinal
adenopnithy; cutaneous pigmenlalion; hearL murmur; neu-
arteries л re common. Shis lalter change is presumed lo
rologicsigns and symptoms including personality changes,
be related to proliferation of lhe retinal vascular endothe­
dementi a., and memory defect; myoclonus; alalia; supra­
lium. Vitreous hemorrhage and relinal detachment may
nuclear ophthalmoplegia; and seizure disorders."'''
occur in some patienls. ТЬё natural course of the disease is
tlcular findings include vitreous opacities (figure lt).5G..
variable: patienls may recover normal acuity or may have
д ^ о.«),^2,ч« ^ 40 ejaJdaLive nialerial overlying the рагь plana
severe permanent visual loss, depending on the location
(I'igure 10.5(5, ti),'' ' 1 retinal hemorrhages, cotton-wool
and severity of the retinal involvement Ihe mosl severe
patches, scattered while exudales, chorioretinilis (figure
systemic complications are encephalitis and hemorrhagic
10.56) retinal vasculitis, and uveitis (E'igure Ю.56..
hepatitis.
Br D, and papilEedemar9afi,,S3? and glau­
The virus is an FENA type and is believed to be transmit­
coma. One patient sludied with fluorescein angiography
ted by an insect, possibly the mosquito. I luman infection
showed multifocal areas of relinal capillary closure, diffuse
can also occur by handling diseased or dead animals or
retinal vasculitis.. and choroidal folds." "
contaminated specimens. Tbe diagnosis is based on a dem­
onstrated rise in the hem agglutination antibodies of the Rifl
Valley fever virus and the complement fixation lest.

VITRITIS AND RETINITIS IN

WHIPPLE'S DISEASE
Whipple's disease is a chronic multisyslemic disease
characterized by fever, diarrhea, weighl loss, steatorrhea..
 1[islopalhologically, foamy macrophages with many
periodic acid-Schiff (RAS)-positive intercellular granules
are found in many organs of the body including the brain
and eye [Figure 10.5 ft.. L and ^ LM]-333'MD 'these are deg­
radation products of It o p h & y m a w h ip p e tii that accumulate
in the cells with little or no cell damage (l igure lO./ift, I
and K). Duodenal or jejunal biopsy is the usual method of
diagnosis, '['he villi show widening with infiltration of ihe
Eamina propria With histiocytes and mononucEear inflam­
matory cells and dilalien of lymphatic channels. AEtered
cell-mediated immunity and macrophage dysfunction is a
feat Lire of the condition. Vitrectomy has been employed in
some c a s e s . ' ' E l e c t r o n microscopy reveals degenerated
rod-shaped bacteria within and adjacent lo macrophages
This gram-negative actinomycete wilh distinct morpho­
logic characteristics is named Tropherymn utftippehi, The
organism is difficult lo culture, buE can be identified by
poEymerase TCR assay, as was done in the vitreous aspi­
rate from a woman with uveitis and onEy minimal symp­
toms of Whipple's d i s e a s e . ' Margo and coworkers
found macrophages fiEled with PAS-positive particles sim­
ilar to those in Whipple's disease in the vitreous aspirate
removed from the eye of a palient with corynefurm bac-
Lerial endophthalmitis and no evidence of Whipple's dis­
ease. ''':"','JJ<i Electron microscopy to demonstrate the thin
bacillus wilhin ihe cell wall surrounded hy a membrane
that confers a tri lame liar aspect with a central nucleolus
is palEtognomonic of ttie agent that causes Whipple's dis­
ease.'' :| The disease is more common in Caucasian maEes
and has a higher incidence in HLA 027-positive patients.
Treatment of patients with Whipple's disease with anti­
biotics results in remission of symptoms and reduction in
the PAS-positive macrophages. Antibiotic therapy includ­
ing tetracycline, trimethoprim-sulfamethoxazole, sulfa­
diazine, penicillin and streptomycin, or ceftriaxone is the
mainstay of Lherapy. An acute inflammatory reaction simi­
lar to the Jarisrh-J [eraheimer reaction in syphilis is some­
times seen following institution of therapy. 'Illis may be
heraEded by fever, chills, splenomegaly, erythema nodo­
sum, leukocytosis with neutrophilia, arthritis, and arthral­
gia.'' u 'U2 [n severe cases, disconlinnation of antibiotics
results in resolution of findings. Whipple's disease should
be considered in the differentiaE diagnosis of patients with
evidence of vitritis and retinitis and signs and symptoms
of neurologic disease or inflammatory bowel disease such
as Crohn's and ulcerative colitis. The differentiaE diagnosis
includes reticulum cell sarcoma. Beh^efs disease, sarcoid­
osis, and other causes of vilritis.
10.i и W h ipple's d isease.
A Lo К: This 51-year-old Caucasian female presented w ilh
d 5-rtionEh hjslory of floaj&era and hajiy vision in llit! ri^hl
Eye. O ver [he previous month, she had noticed floalers in
ihe lell eye and fun her increase in [he f letters in [he ri^hl
eve. She find undergone bilateral nephrectomy anti renal
transplant for polycystic kidney disease. Sbr1 was on aia.-
ihioprine '1титаг- and prednisone 10in ” per day.
She had pneumonia .3 years prior and had а coronary arlery
Ejypass g r w 2 months prior. ih e hiin had intermit­
tent recent fungal skin lesions. She denied levers and night
sweats, ih e had mild itrlhritis- in Ihe knees.. Two vears prior,
she was hospitalized and received IV antibiotics for a pain­
ful boul of mij]ralorv' arthritis. No urinary, neuroloyic a I. or
cardiac symptoms w ere presenL. She hiss had problems- w ilh
irrilal>le bowel in the past bul duлied re liv e jjastromlesLi-
nal com plaints at Ihis. time. Her visual acuity was 20/50 ir>
the right eye and 20/25 in the left eye. The vilreous showed
whiiish, Ihick, snowball like d eposit, m oslly on lhe relinal
surface and some in the inferior vitreous, more in the ri Ijtil
eve :Л i ihan ihe I el I eye. Thu left eye showed perivascu lar
white fluffy balls 113^. Her urine culLure, blood tultuife 3-Ч1К
from aqueous and vitreous for fungus, HSV, HZV, and vilrc?-
ous biopsv w ere negative for fungus o;1 lymphoma. The vit­
reous biopsy was reported as rare macrophages w ilh very
rare lymphocytes. The fungal cultures and bacterial cultures
were negative. She duveltkped a relinal infarction temporal 1o
the fovea i.C'i, noted 1 dav posl vitrectomv. whit h in c lu d e
injec tion o f amphotericin and fluconazole at Ihe end of the
hur^ery She was Started on ora] fluconazole -tOOm^ pur day.
dcrttycyefine lOOm^ tw ice n day. and LrimoLhoprim-suha-
mothoKa^ole lHactrini: iw ic e a day. Silver slai-п for Hindus
was negative. There was no evidence of ijiatlrinancy or viral
inclusion parlicles. Ih e acid-fast bacillus slain and FCFi for
CMV, H S V - lr HSV-2., EBV, and Toxoplasm a were negative.
Two weeks later, her visual iicuily improved lo 20/30 in the
ligtil eye. Vitreous was clearer. The area of retinal infarction
had resolved. 3-luorescein an^ro^ram showed mild cystoid
m acular edema ID and E.. iis weeks lalerr Lhe inllamma-
lion worsened and the vision dropped lo 2Q!J>(5 in lhe r i ^ t
eye and 20/40 in the left eye ll- anrl G l. Huoiesoein angio­
gram showed w in d o w defects corresponding to small mid
peripheral l iit>ri ordinal scurs (H and I . f^uanl iHtK О N -ТЕЗ
Gold LeF-L was negative. IgG was negative for Toxupiiism n,
C.MV, tE3V, and Kartonpiia. A repeat vilreclom y in the lefl
eye showed cells conlaininy large nuctei (J and Ю. The vitre­
ous and blood P t K was posilive for Tr&pherym a w h/ppeiii.
5is months later^ her vision had improved to 20/30 O U w ilh
nuflear sclerosis following a single vaneom yi:in injeclion of
1 т ц anrl IV cellria\one once a day f-cjr 1 monlh, follow etl by
oral Lrimolhoprian-sultamelhoKazole hvice a day.
L: t'holomicro^raph idhowin^ t luslers of mat rophages w ithin
the inneT relinal layL^s anti in lhe vilreous lam m l
M : Higher-power pholomicnograph shtm'in^ tlu sleft t>f m ac­
rophages w ilhin Ihe retin.i (jrroir*).
■ Д -К, Г ш т k iB W ijfa te l 'I .il ' L .in U M Ir o m l o n L u l ,il 1 9 ’ iV
A m e r ic ;» n M r d ic ia l A lo u t ia lif in . A ll re n s v E d .l
References 43. tttea A-. Ш !1W. Najor^ Ш r ciH iok. . fel air OahlTElncl ilm saruE' 939:22:196­
205
F»jer AJ. 'A'ergstr ТА. ftmir:. Gft Rib iaiрчпзПйл! is Ear^ sign of EaJenal 4]. F. Гииг £f.'. h lid i?n 'j e; al. qpdTei^daTCJXHlaLfi r ffVrtBdtai пкрйь'шеал-
ft cairma irhs Am J СсПгёи™ lS62;36jffi-7l. KialiJi C6ay!?LaTCS! 1902:1.S№
2. Elxi ЕЯ -ft inn f.-",V. Hldsn Ш Gaas X . :,E;umec torctia- \ ta хйй s mа human ^2. Еадшы U. Wsjiiei'j H. Bal ^A. GiiE-i-Cmas У о к И-я й 'nasaJte as a campiejan of
ranunateliciency ипл mleclsJ hcsL AmJ ОэтГапс! 1339.1C6:E№-7. Litacraia- ciseaae. Kin Mcnalii ^Lijern&l-d 2MH$225'4fl6-7.
heiact>]n 6i. Ef jckst Erabdl: EthKitw сиз К Ооутесазети i mmiEsintл Ziediiser F.ezrlz-Sch'ncl K.U Й з -janF. Seo'rtir/tnalaaigauo'nianJijcu'ainnnE
B-caiiincrjItJ. В1J Optrtliafcnd 136669 29-21 arrp(d т а р ^ й : c! al-sdsnch Jiease. Jpr- J ^ipTJJisfma
A. Квтаф J* Ш и G?-,. №lcqHflMfcfl^QHipjltte of retiia fecn:: SLbacuiE isflenal 44. Masinll J&. ^Eina.ndcflic тег^гй^лайсиапата' aisocalecittlhcal к п а
Efidoc^fcAniiOptiBtalnKl 1ЙЁЕ:74 653-62. n-A-fxeti'ilE. Fterna2034:24:176-3.
5. Lfis ■f.- Uebef -ie tei йг aajdn i e I спзг- Enttarals Jd экзегап 5йпатеп Elairkjrgei Ai. GussnWaus HE T t a t scraltf; dissas-t:» la> art^alM s is f e Am J ОрЬпЛкй
лЮ стталет ftenaba a-jcfungen. Bar [fliltiamsi Gas 1S77;1 Q1-10-3. 19&4113:246-3
s. Mjjst 1 Clha'iTGrifJP Sbb'el па (jba^aration secondafyla ctonirti мр!с iS. L-:e:<; ЭЕ. ВкегTIL Едж 6M, ef ± r ipfl'fij ckShaaraTCian-lhe N-a:a.lif л arei^ty n
masaaftsi; (memacute ta^-jena ЕтасагСпа ffetre 139^2.108-1 2. AIDS mmlEs^ncfcafscialEhcbeaKDfbaaljS nl&iDn? лодМЁвб.' 960-2.
heudariar U Bameifl Sets' 0.Э&РГ11Л- qrav Fieliallesicni ifisegteema.AmJflpWdmo Al. EtBcrf.'H.&Tl^iC'RElfiqhiM R“ Fe'e ri: Г/. Ал aJx:janscts iTeclin assocm&d
lafeYlfcTffl-Sj fliriQKJLTEihnm'je iHbETfr Sindmnte Am JCln -affal 1ЭЭЗ;ЗС:7'4-й.
6. FjcTi J Л Betase zu to rte s i°: rancosm № ( Ы | ' ccr flaw пнгг. ftrii faitoi Am ^B. £ajef n rtarsruni V. .аЛис 6 s: al. tass rf рагамк ^галнгиЕ а: а ш ialu'e rf
PlQrid lflJ$£197-2V. Lvne dsasfi.Cin nf&:r Da 2->3&:4S.7b5-3.
ft ftrtiM Ueb? Hebh^lfalicflibei Wjnfteban. ttscS? 3 ii 1272:' J 7l 43a M ld(teSraala,ai21)00
to ИвпеИХОЛн1FH Greer ЛТ! Whte DemefBdtraiooliagEsiPftf $ш1кагк ОртЬпОмц1 43a Fima id . hajges, el al 2tOl
1360.67 66-3. № |&ta,№f*el!ffla2.
11. HiEam Б.Цтт W, Щипал i M ffi&fcsifoiHiafrilfc.Bt Jh a a Med £якО 49. Aibera TH. Tte ежатах сртГдГ"й1с^с sraliur cl ж е -issss Air J Criithafcnd
2DC7:ES.424-6. 1Е69Ю7:7У-Э0
12. [u'.'s JLM-ssa^i]rrFft.Satnmar Dfa eiai. ВихеплйЫатепй leirna г A£E. Am. 50. Eoighitf J. Gasser fi Fag В Op^ahic nan fesialcfli cl jIte ijxrdkxis: a rif/ff.i J Щ н-
ODiJrair,-. '309 l07:El 2-23. ОртГа.-fil 199^.14.1 ь-20.
11 GctGE Lev,ish.^elBirj;ct>]r'>J2l iK H EaijctH '> dil гакаэсиЬг membrane asabatat 51. EjslasierticjAA Fjupradil l^ 1.rtaj jam GOH EJark -. 3i alaiai il ftta afjcrcib: i crd
*№ aaffwtoooccus a j at.a ento^-llis г, а тегсп user. ferns 199^:14:256-9 ELiu-lUr^e ra id -ttadiiTEts ^th e t e d Lyre cisiaae. A.mOpitaiT]! 1933:
14. CaiCE,* r.1D. Ocn:bs JL Vtesch er Vt С 1 0 ж й dram спе. FKlrn 19SCr '027-22. 1C6419-2t.
16 Kf.jE.LajdKifii.Corcar J U i Kftin.Li.EPdomaLErctiaj тмшйэаз JAAFOS 52. Ей5e%sd J FtlhJjiA Kiips1H IrtamalfltE Lfsrtis and Lme ит^гаь Er J 0Т№ ать
2№4:6П94-6 130276:131-2.
16 Бйгяодъ E, ''lira; 6 Atoa W,ac al Cicfcfjal atffiass dje is Tcar-ia i ^etfат m а rena 53. JafiDtscfl ЯЛ ftas j 6 FlseLd']r'.ti,or sretn i^dnnie авм айз wh Lhimedsease Am J
atqiall re^p crn. №.\« 200±2^:1 Ontt-artl l939;lC7:fi'-2.
17 LUjCita H Fijnhr: CJ, Lcten.. £ua n id аз&жа и г й Их j a a la-} to. iirecl ai Reim Я . Leaser FL. Konr'£h ЕЛ' F‘aJ t s АГ ec aljШ к ц Н Л а ire eg с isarreoate d L'fie
а а д зьр - Г 4 . djKaM.OptilhanoDi^' 19^3:37:699-706.
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hScftffrtajKfr Er J 0зтГй(та1 l9ci372:EE-01. 56. iwto JL С тп и т Hj a tr J. 'Pie Etiaca^i Palier Eye ItsI imls ^ тгЕ ^ 1 е апле!1.J
p &еыгFU. И, JU, et a. Eiap atja httard; елгелег а±гйпа] зЬы ж Oh ftftjo-0[l#iahol 1390:1 ЦГ25Б-Й1.
d^'icsed ?/ trafafrcaJ ii nc-rsfde щ\ "лШ\ ti [fбу. Fiehi Ш£:9[" 13-21. 57. Eirn JL pLirstrs- TM. F^r^-ltiiinkn A. FD'KTen FK Tre гя&г#} d L ^ t dвам г a
21 tsVUici T №ltandKF. H arm m lel a. Eidcgersji ^окз^.^^йгаизтосгП ^ Чв г na cn-iiric a ^ a CD if-tiraleje KrcJogic 9it|f n a scun FH ca eye a h : pajuancn. J Ctn
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22 . J]n j^ LW. [itriti 3S. .^ImtI DV1. 'i:!nsx u' [юсанАв&Дт J Spr^alriJ 1&73 53. Eirn JL Hhward kf. csoi Lf. Al« 1 DtV Fielra voacu il g ш Liire >araicaE, J Cln
Цай>0|М йш й]Й111:7-15.
23. Щгет G£, 0 GradH Fl ChufamoteB LEndogtnais 'пх.oJti 'isiiciiasteicnei r 59. EullDTi-6:nu щl MSA. Lrna'id К .лап HamA3, ef a. Ei Tlshsr clw crelinaatfu a>dLvkb
dseasE.^ir J d=r-Efca a Air J Optittdmd Ш 1 1 6 1 49-55
24. M?jer 3s_ Fcfil FL. Зпамег !№axiiar lo cifJEfi: u i r c^ inres ы зк. Anti 0 ? Та л'с 63. l№ a tl ME. Emit' J. Ct !зггаа' Ш FtiiE-Hcirs 11A ta.lar jms уя З гш -.Ат -
щ й а н :. OpHtaftBl 1939:1Cfi:E5"-7.
26 Fl: i IE Ш, 3h e cs О.. Siietls-f, e; a. Mctajci: t ™ id atEtess. 3f J Й1. Fjslh nam 39. :tu ar irailsslal ста зг Isresp-iie. J Fisla'aJ Med 2Ct6:5l .139-34
l^-.7(3i39^c. 52. FslhramSfl. Ocuarlfplcififai (лгО зг O jtfiajn 2W2:13:3Sl-t3.
26. £ter 1й Ш Cif. Efrq Of. Eaalad mracoJif 'ЛкгийаУвгс^е i 'eifln.Arch CptolHtmd £3. Falhnamia.-Hum^'am > ЕГ lireas.fi'aiisE: Df L^ilsm lie oevel^w dd.lm
1377!3E Hlfrrffi Ортга гя1 С =n20С(;:4СГ 37-52.
27 №i$ Miieo-BEeai fi У!глэ' M, Aal £i;a:es:lLhalms^ d 11«ап1апм JSBfan a 34. Martre ?,K. №tma Kl. за 51:a MV. d; ftiti KIT. Ccja1marrissla:-.^ т . lie aD.te ptcae a!
j c mabcbii хеиш й^псЁпШ 'сиг^ш ! arjeal iranidani кЬаШУ'аг^атРТ'З; leptepiitias O il immuTdlnlbrm 1396675-3.
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na fiEhrg (ипгик Г; inSnaaa. Меиdq FaiEKJ til 2COS.S2:1 334Cl
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530. CtBooih J.Ga'nrti J 0р1Та1гшц1зак а e-. пгЬзжаа (lefe'e'KetoGocihDiri'a
to n rf(rtL C'n Inlecl Dts 1992.14.444-9.
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532. CLw. JM, \ViiWer CK teen Jrt ODfTi ncufrcas imerra sailed t^1Culeretra lar#a. Trans
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535. Bara Cfi. DeviiKirantor Cu&etrajel im i nplsra. сJjeret^diii in ;u species d rahb is and
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535. Raft:a Pn R i Seiierarc- RJ. 'jreei 'Afl. №всйп^ Ij енсв cn ■ :ЛnTact Л tr:i
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535. KefilH' RC. jh ih rw attara KE O'bcsl nj aiis. CphMmcim 1955:£2:12^3-32.
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Я1. Zienans-j MC, jee p,V, ЙЬа:es R J. С^Мактитэваз [гтйга. ftrtJi CphtraJ rrri
Ш Ж 633-9.
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543. Sy^slsi P Stench £. ODilha rroir; aa; luema х^йепа. Grattes Arci Cin jo CphlbanoDi
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l994;HM:1ffitHfl. ' _ " 594. К пр. Йъпр U 0 LorettJf W.A Э-wear-okl d l я № Irenes з ггр1е?: ^ns^pa 2aorte
655. Orefena j. Teen SA. Ьейтсап Ffkl el i. frealmerf rf retnal detodimerts 'П iiLats w T Ihe
адш ed immле deficiencysiiidmme. ОзМа ггс cg^ 13 ? :98 93M5.
6Ж. Gieleraefl L Всекш1 fW.Afcfш к ^ ™ ж а 1с 1^лзеп-1 мазе Arch talhamsi
l*7:57:3t-9
65?. Энчпз J в, Fa fcstre AG. to n g jfj MM. et al Fame cl згдог bser Tow qtonegaloMnis
rednlis,flejia Ш ; Ы 1Э-22.
60S. Ms"f M, - iiiifr i I t o £■.ecal. PcVrerase cnan геэЛг HerTe -tlElEr cl lie лпкЕа-
лйег gsicflis n acu ar surples fror: pakils nid' aaJte 'el na: п&ж^5, . OpTtafc r.\
1992:1 H:№S-9.
659. Нлгд Л , Flssscu1.Fkns-AgJ ar H. e al. E ^ L a o я сиа &3с ip х п ±ъп d
dn> e>c£fiv£na Лгвсщ да^.Нйп! 1993:13:160-5
660. Marin BF. Ctiai C G. oeSniE fit, г al Tre ret c! diatfelraJ n ttis raB^m ert al
postHiof ureits OptfalralqiYlS03 T>3:?0E-'-
601. mrisAM, Sflil^- Г.' Fselil DW, et al Тле s ftalea ййшэзг cl 5 гшы:? repii1ficl&n is i
preccu la bKflSKfial тапепсе ahs mialcf'Deae^flit.Cincaf qf+jencl млакегз
РвЯМШБМИ.
№. Сbis Ш, R™j-T. Daiis E i -1-jss ;i ■ ?ли ®1nos, Aren Gfhlhi md 1 293-3ffi.
663. Caan S , kj.'jtinara Т. ^ n p Щ s. al H s k з n'plei. redsBpa^ in a' ixanl. Adi
CfM-Hlmcl lSW;fflM1-Si
604. f e f Jibs JD G'fits U Mil lowS, et ai ОсгшгЛ rerpes simaa rei rjfc ftit J Ccni'iiJrrd
i 333:1C2:33t43.
605. ГчаГpias A., -ag er ■'£. Omcr ran leslal ens al ^rpcs amp & i -te Tev.twn rjeanala
ccda Tcipes;. nl ОзГ+а rro- Gn 13?2;1 i. '91-213.
60S, el Атол' ?-■ f/a ir G. Fasten M. Lai; cflTT-alr cfcgc ma ilHtea'fi rf neonatal heraa
SFpfci'.i'usiTedcn iT JG^ltiami! 1£9Cc'09.l--7.
667. Cku S£ Cafa^an Ш Eisii CL e al. Geia: j tu Щ ъ са г Lh Ьй.: i iasi mda: m xc
US*m Hi JcV.eniir^tnh:. 300^200E:4jei^uiiS ftir JGtsiel G/ieui
2 Щ т .’П\ |el—7.j
< OpIrthdnBiWs^i 1933.1 £lEu^,i:43.
603. ЙDon J'J Kaiz J . KaLlmsr, HE Hetи 5rrplet rebmle ire EToediails m т.arWL A-d"
Opfonalmol 1Э77;Э&17Эа-Э.
6>39. Giutzmaditf ^D. Н^лем п D. Mtflxala PJ. et a. Herpei amaa dutaEttitia г a natty
aitit кл J QpifahBl 1933^:738-96.
'ЗТЮ. Рагзтсл LG. Mora <ler KZ. Hstjs sriptes где l rein! з n ar. adJl Luln SfStem с
be-pes гв й . Am. OpnTa m l 1931^ 21 '5-20.
671. Oerters ^cr CiiHae CtfIrel B-v r^ п1ео1ет r luunaa Pena^ia. F& ca MMWR r^-rt'
fAirtaHI^'fiep -98f73e^afl-90. [S6-^SJ
672. hjflv £P. Fjcsenncl flfi, fo'Mm <ь e; -±ranocJm*ffis ir, aaie ^зйп-Еат 'лп-^з
intfd cn. Bf J OptrCEhri l £fi£:73:l«2-3.
673. Bin er IE. Млпга 3S, hve AR п а и s j e Iet Dftlhamicui мг la alsfa te'icM'sgic
ledoDFalTf,1.AmJ CpTTal icJ 1951^ W S- l.
674. CJtalsan Щ ^iLiren-janz MS. Th; ane rettt c ^ a s з/тог-ш с. in. 6cd F£ sou
H eixsaiiT ^ iT ed cnirT jefr; Ш М :Й т Л 1 У 1 т д а н к l9 ^ .|i 7: -39.
675. EiOaal'X Af. Hems ж е т cihiiJnicLs: гзн1 а! ж ® ano review cf I laralure. ftrch
OptrtHliiBi Ш 3 4 ■W-SJ.
676. Hsie W herras 3Bster «ИГа iru s asactaieci win v ,tifld -sl na irrcm ith et ns. AmJ
0(М н 1п ^ Ш ; Ш з ^ 1.
677. Jra-sen J A. case a! nerpfls zcsler c Jt a rra s t]*i pi^aieJ и lfc nancfeli tli3. Acla
СрШпю! 19«.26&51-E.
673. hEJLi' ann G, 3iss JDM Fa t RL. iit&siltia ад у Г-йт« isslei 'itilhiim сJ 3. An J
fiptoalmcJ :196fl:65i533-41.
679 Sch.-.al; .N. GaclrKil F -^tns №: e! i. Weadizr^ lelrclifth Htn nei)ie; :aslsr
а Ш and ftetiiii friucainaui sk K AjiIi Fatw Li'Me-]
1975:1 CC:366-91.
630. Rift'l SM EnaJy-fJOji. Mu Ulxa cfaciGd s jjeds cocumn^ zfter пг-ps м к г
qnralTi m Ajt J Gpmnilm]( 1SfiS. .08 733-5.
631. Laitart SR. ЦЮг G, <issA e al. G cJa m a'iieslitia ste д "cen lal w h k I a ^ndmmi
ATf. 0pTtial"cJ T O ; I C7:EtMi.
632. CiCGiB J rA. \taecm ТЙ. Gerlral -ia l lass cased tr; 'Jncken pop: ran bs in а 2-цтеа а d
cUd Am J GftimJio]! 1 £S2:'.13 592-2.
593. Gto К ran H. ^em a ren al агег,- осиjaicn гег 'лпя1 а. Ач J Dtfdiamai
1992:1 i 3:691-2.
Cosmi'.er RM. Gtd^rptr ■.if: retmcpaTry. ATti OpMnaiicl 193E:7& ' 9Э-2И.
635. Fnfrbre hiA Mсаг W. toacu ar Etndtejs Immсгтн:.: relira srter: ooJ.fi cn asacci&d
wtti рж.Агг J [i*lhaa:]{ 139l:i 17:117-&
ЗЭ6. Mu-Jiiis-Jce ЗЕ.'Л'аП i.. Efanth гйгн! a triib i Krim Twtti utitten-jia: Er J Отаапч
1ЩТа;7В-6П.
597. Amiral lA. Cart JS, Green FO. Acjfe phih as buh ifd ertsnal cfhinalmcflegia in Ья^-ез
гваегм1Шн1пн1£ ftrn ^*ittiim^ '9S6,17:45-5'
539. Gi Ы Gd. re ps 20m opcihiini сjs а с гагiralatera ireKi psrsc: i ai enshp cl
t iyifcfflie !■cerlral rerjcts cyslem crirutfflatots ana 1! s. JAM^. 197^ 229:3l24
Ш . W oirai Ж Osss-jmaTJ Cofrcksjliorsd Iteraesauaef op^feteiffi Arch tehttiftid
1993:1С .42-5. '
5M. Men R uiien-^fcdtf У Катжп E, el a. Aate -s1па пкгкй in piimay hEpa ifffe i чл s
т а I nledHi. ^eciar nlsotDsd 2CCS23:153-^.
591. '.jael L. <asf L. Hfid-.M-. e al. HЗ'Л acui; lEini; na-asis. riic^asfi j C mjnls' rq ^тгГ-
щ тай*йм (|(пж аЙ с№ reactor. Ini Зсгйита 3C(929:l 9^-201
592. 'ilifttercam T. linlien Fd. de Bk 1JH. k al Heipelc erjKptidil sis a nsKVictor kf a: j s
rEinai iHiiisi;, Meu-ao^ 20tfi:7'.:'309-74.
593. Moessn:. Oneiric £; A.Ehs W. ftcue гз.па necmsis iesTLCiv й heiH siiptei v n.s rroe 2
4)lh pasting ct» се! ra scarmg. J PeCuIr СрШИтз! Elrab anis 2>]Й:4Е:&9^1
lEinal nsrcsis irea-a: i.iininl^rrealiMcame.Oailln niuici nliairm 2tur 15395-&
535. Chang S. ftug ih. Acule letnil песке: an о ^ е и . mi 3ffltTJma Clh 300’ t f :14&-54.
595. '^n jelcer RM, W |h jl. №bnd EH. el a Herf<i: ama e<- x ы в 2 is ?. case al а л
ге:пй пешжмтпнпе^'уалп ЁйнтЁ.АрЬМтаотЗОш lJ9:E£3-76.
59:. ''зтатато £ hJafeai Т Kajwrna К ^a.ts relial ro css nit^ cp heraes srrp ек e^csfa Пн.
Aren Kejd 2t07;64 233.'
593. Usui v; HdlDH. -1>лег; ь.; and сссп-к s ct хи\ъ 'E na nscrcsii smk&dtie. Semr. Opntahcl
2332:23:275-33.
599. 6arjda <,hjnasTilaA.Mmja^ 3>: еж з -Df» caied Ktisii.ra hae urafe Jpin J ОШ
Oplrftdmd 1£79531515-2'
7-33. Bh.rrsKiranz MS.CJbsnsm'.ffl. Cla'Scn^G.era. sen! огте acul;rennil li'a se
з.||Т>±аче й1!п :пГаг#яnus кус сл. ОзГШа^щд^ Isfl695295-2C9
731. Вге, -п Ж r^end s U. Rfttil ?j1sU: acirn sak'd herpes zc-яег cpIiBiahiaf Ei J
О рШ пй 1£73^67 3M-6.
702. FisJh .R Lews ML Eiumertir^ М. e al. The aa.tM e! па' г &ж з е s/w art. Рзп 1:3li!ic3i
narfeadHis. ODfJtbanmicgN 13e£69l309-'6.
/■33. Friberg TR J ce BE Aate reffial nercaj Lri a: i i iLnasJifesseo ca: ет ftir J GchlbaJmol
13fl4:M:b-5-7.
7^. GalTf DS. £ta ton j J, TL4?y A el ii. Acul5 rennal neeasis ardreiB Er J Срт+акШ
1991:7Е.Ж-7.
705. Gass JDM.Ai.te heraelic Ihremxte relmal arg ils aid necal лпо пьшепп lii гасив
rEinal nacresis Ejn:reme ■.^кгрозиг anMedtal ач: S iig a Diseases d ih^Rehnaand
Vilreije: Transanxs Лif; №■ OleaniA.'tidaif; cl СрпГа1го1сд^ a Ldjs. Oi
1932. a. 97-107.
705. Giunn Ю. Mas AJ Gdes 3E,Aoule 'E гa nscrasis. З ^ тзтЯ о т
ШИВс809-И.
707. Наутеп WMi. Kaffir AL S-lnnHsma ЁЗ, et al AcJs relial re j 'B s АЙЮ ALilras^. l^esl
709. Ha-f’en S3. Acule retinal necmse. An1J ЗрЬИйтэ! 16^4 97Й51 -2
709. Ha laid Gft. ж е л л Oammttee c^fcs Aienan 3S Sc^Ey. S^dzr j dagiaslic j tens
w he aoiils rnrd necniiii ^riirem; Am J CphlnalTBl 1Sfl4." 7663-t.
710. Jampcl LM. A^i Ie геп З necresii. A", j 0 ? (Ьалч ' 93l2:93:2&4-5
711. Kor'elai.. Asif amaT. А азе oi specdt u^lcs oesut пд асийц in Te n jt e^. Fs й
GpCltoilnii Xf 19-71&S91397^101
712. Likin a 1S.Acale relinal чесгзз a Itdfcoria:. Er J Оз^Гатс ' 991:75:44&
713. МэпепЕ A-С. Freqjence el аэекз dnqxs, сез у;таюа1 ens relneroes te I'u^eile
iiilffmedam.BJir^m StcFf ОрКаЬтн 19fl&9£40-£.
7n. Gk nam %ТзJ^ ara I Aole se^m js иa v; № relial 'aiscujI s ard -el па СЕЗСк^т.
СрПИпяаиа l£79' 79:275-S6
715. Pice j RV, £ch aet^ J rT: E^lersl aoule гешз! necresis. AmJ Otflha nm ' 930:39:419­
24.
716. Runnel:'/ Wert*! -. FLmmeil C. e! 2. Celetltfl v va celа :зз1я *г& and v raJ
ал1мп n ra e e a a e c f biialaal acufere^na necmse SMidreme.ArenGchlliilm'Di
199^:11 СГ132-Е.
717. San <M. &:#e 'S. Г.^пП^' НДec al &fctem.: aa.te -e; па пкгй s, Am. CpnTfliTcl
1932:90:403-11.
713. Srar'L^rg У ?, hm D_ Fnkelsian О E il. Acule rennil necmsis andante Relra
1992:2:145-51.
719. i'Dpim mVfhsdHUBiH FreaSn -M.ecal &tteraiaa.le reli a гкгсае; d ra la n l
Lilrasln.cljrsl SMyArch З^йатгг :9&2.lOO:1fiC'-3
72,3. Ura^amaA, '^ adi N. Sisi- T. et al Ltd ateid acute mens v.Mh ie! ra ce'Gnenlis a jd
detadunat Jpa J Cfn 3rt lharei 1£7' 25 Й07-■9
721. p : er&a Jr D Anaenc TW, Reese1b-. Neotfuiig л sa-aoaJ34? relmlG.An' J 3pt;llii!mil
1977;fl4:2D9-19. '
722. vau;g HJA EiidAC. Eialera aoilsrenni! песке. Ei- J З^Кйт^ 1571&C2 5S1-90l
723. Gu Lolscn Wi. Вкгн М ш M£. "anei H el 4 .Ths аале relial r#^aas synJ'ane. P-al 2:
HGlipalWD^' and eOjX-v- ЗрМ зШ эд 1992:29.' 317-2E.
72^4. Krcols T.itinetf.Hjfn tfr. ei Acute r^ixii шитве andrnqti fresenipgviT-failns
and aaiate n airn J rate.. Qjh Ш mrktji 19fifi.S&937-4d.
72& Flag I'c CE. Sera® PC. На AC. et al НнпафшпЬ а le'akn; г lhe асле reins! lectк s tG6. r.'cCc-i^j HR Lem; H ftet^r AL e j|. Sl p je I Tccacemsrl al roli al cfllachnenl
Esmmms CpTTafc^ict-gy KG 133:1171-6 asscosrtet- -.'.inet-JDe reli-al recr-DQs synJcc^e. BrJOphttiifod 1ЭВ176:45E-6
7£6. lira 's Y. Ghash V. Iterлз T. el ai A m fcrfl.e Ггйт ft pa! enrti.nfri г м » qm talriM 767 Kai D5. Atrami ijft. VrtkaiB GA. Reciess cu ]i cii: re'jfiscu anzax tv phaittag Jal ci in
AmJ<Mi№ntf19e£ 102:532-6. trе гсл relied neoc^sjflthmb -elta 193Й:Е.244-а.
lit. Мф1йТ. Ш а р п в T. й р п а T. e! a.Aprcpaieciint: fsps of aate 'ema nectras 763. Sergat; ^C Ana^c F: Efllrcni .E: ei Л.Aculereinil aecciii narccarty cs*alpfJile and
arcrane An' J Cfhlhamd 1£36:' 05 579-51 aif-jaal herap» Arch 2pl;lhalniii 1S69 Ю7Й32-6.
726. l.larauo Т. МоппнИ» К. ti&ud N. Fascia asaxeled with pmr ista ш а те n at J e reiial 769 Dj ‘i ' JS. 3 a4 i ER Faa cf; j асгеик am rs id netrtii; h lbs acQLirsd
necms&Bf JtyMidmd 199175:45C4 hnjjiDdefioanатташе. An J Opahaivd 1331. \г :256-й.
729. Fab nmtEi T. Hczit RA. IfererWS MR 3i alBrai acute renmJ песке яткйпа Am J 770 Enjslrcm „т R i. lialianJ Ж fhtucaU F el a. l e ое а лег гег:па! тесаке
ОхТанх '933.133:766-3. aincm earaiait с! TecTfshchsuebarelnDcafnN n piaeila^lt AJC6. О а^та-ггао^
730. Fa u? DA 31*iben; > P, Cdms ... e: al. Оесгеазг ;n Ihe rdt г Li Je'a. m le slJial necrciti s.. ’■Щ101:148В-ЭП2.
x u m r Ihsif у. AmJ ^Ihamai 1991.112:2EC-& 771 Far:ie- О.. Иде Fu Fiai^sl' GT. el al. R:n cl^ атае^^е culsr -si r J necraa: r ire
i'S-. Cuaeitscr rtW. B tma Ji'aii MS Рейсе J3, el a. Uariala ш г v п.а а а кш к a1te aaqured torm idefm ra sjiftdmnft. Amj С ртГаЫ l?M :l l &S41-5.
a ils m ail пали; syrcrcme ОрйшгаЬду 1966 93:559-69 772. Jtfnstn Ш, -о la"c Щ, ncsrcn J r RE. tr. al. Rsire> s of prea.n:ej '^oela-JKef
t'JL Сиаепиг Ш , Ebd FG, Rorn Л -\4. el a. CtiiclHipa£™da]£d aziile tma necicai MniEre!i>]ca(iTf/ г Mtti иигеа i ' t l n :« Гсer :y jhr>t:rt. ArnJ U:t №uм'с
м ж ш Opirrahclc<ji' Й 1 9S:lS41-5. 333:116:42-50
731 Ja ti DA. SchaiJia! A;. L& F: e! t P'esumec «rice laZBEJer lelnlfi ir imn.-naccmxaniie'J 773 f.'a'ga GE. PGff.i Ficgieisf^e culr relrai i ecr-atss s^Khe№F,reia_led a: te ■Jeitiaef
рглета. Rains'937:7:9-'6. Sca^ ^teelrg. 19Е4У
734. Hel> SR ifeffitTfllAR Счгкгрш dHKfetHi vlis. 6- J Cf lillialiKl 1£S&7^j695-£. 774 Shixda K, i™ e M l;h da x et а- РгсдгёйиЕ ctle- reliaal re^rze a ma paien! Ait' пеэпсй:
72b. Masuo Т. Корпя \1 f.'aiiua ti. Actle 'elral necrciii а; а тс+е nmpI cifor cl 3\гш pat ичзсАе. GiihhalKic 5x j Lase's 2031 J2:6f-72.
r adЛь J Op-rtak-cl 199Щ 443Ч 775 F k ! s IE . Peiersen K tL ^ u ia M L a al FrcgreBhie -sier reinal tsaaas sjntfcime n a
736. Yea JH F^|>:ft5 J3.Stewart JA el al Асле relral re ira sщп*эгое la ймпд Ге^й :aslef ix m ralierl « h good ^ia( алапе. AmJ ОркГаГй! 2031:132:'' 7-E).
dffln^.CctitaJmotogy '936:33:1416-22. 776. Ka^w/iaeH. Sac T. ifcirajch Y. el a'. Frcg'essne a le ' reli al necnoas cslsa berss
727. BlA^M .am uefeatiA лае A el 3l. ПйаЙш 1ал1юфрпкШ 1тя}^Й1Ж[|Ш е im aeiKim i^e l n a aalienuihcc^i'S]immjcdecaa^^^i crcine ОптЫнк^^
hsaesrui 1агч у h ^a.le anil теяоаг я/гагсте. AmJ Otflhilm]! 1331:112:7E-££. 2 Ю Ш :7 Э (И
736. Мэгаю T. lale S. T;u) T. el ft jrirune юпиек corta i -itc Ьеткотх s&jen it a naier t 777 Yang 2№. '/.‘олд Щ Un JrP. FrogmsfHe -Duler reli al reacts ^ U -j le к тear4/
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h ibe -наш; asp rites cl piierts wit; Э'Ие rmnsl necraiii ^rcicmi CpTTalulcgi i 79 '/nebs Pcsjeriar segmenl ma-de^K ais cf №/.'AC£. Зит,' OftitiahBl 2УШ $: 31^7.
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This page mtentlonaSly left blank
Inflammatory Diseases o f the Retina
Noninfeclious inflammatory diseases of lhe retina can be
isolated to lhe retina от lie contiguous with its underlying
structures, choroid and sclera, or wilh adjacent structures...
op Lie nerve, vitreous, and the anterior segment of the eye.
Jhese diseases can be idiopathic, autoimmune, or possi­
bly an altered immune response to an infectious agent. A
majority of them are isolated lo the eye but some have sys-
Lemic associations.
RETINAL VASCULITIS AND
PERIVASCULITIS___________________
lhe terms "retinal vasculitis" and "retinal perivasculitis"
are used interchangeably as clinical names to describe
the fundoscopic picture of exudative gray-white sheath­
ing of the major retinal blood vessels. The relinal veins
or arteries or both ntay he primarily affected, Kluorescein
angiography shows evidence of perivenous or periarterial
staining and may show evidence of vascular obstruction.
In using these terms., we recognize that the primary cause
of the fundus and angiographic findings may be immune-
induced damage rather than inflammatory cell damage
to the permeability and patency of the retinal blood ves­
sels. Elt’linal vasculitis and perivasculitis may occur as part
of well-defined ocular diseases of known cause (toxo­
plasmosis, pp. 848-S!>2; diffuse subacute neuroreLini-
Lis. pp. 864-872, cytomegalovirus retinitis, pp. 832-896;
syphilis, pp. 81Й-82Я) or well-defined syndromes of
unknown cause (sarcoidosis, pp. 1022-1026; tieh^et's dis­
ease, pp. 1026-102S; acute posterior multifocal placoid
pigment epilheliopathy (A[]M PPli), p. 954; acute zonal
occult outer retinopathy (A/O O RJ, p. 5S0; pars pi an it is.,
p. 1036; multiple sclerosis.Ij! p. 1038; idiopathic recurrent
branch relinal artery occlusionr pp. 474-478: and Liles'
disease, pp. 564-568). Other more recently described or
less well-defined clinical syndromes associated with retinal
vasculitis and perivasculitis are relinal phlebitis and panu­
veitis associated with viral-like upper respiratory disease.'
frosted-branch retinal angiiLis and acute multifocal hemor­
rhagic retinal vasculitis.’ "-0
11.£>1 Acute retinal periphlebitis and panuveitis.
A-D: This. 9-year-old boy complained of blurred vision w hile
recovering from a r acute respiratory infection. Visual acuity
was 20/25. There were cells in lhe anterior chamber and vitre-
uus. Note the relinal striae in the macular region (A). The left
eye s tio w e l idnhn1ical changes.. Adenovirus- was cultufed from
his throat, and spinal fluid examination revealed pleo-cylosis.
Angiography revealed leakage Ы dye from lhe oplic disc nnd
Lhe major feLii>al Veins fB:.. iix wtieks Liter visual nituily, Ihe
fund: jand ftuorcscein a ngiography w eni normal iU).
E—1: Frosted-branch angiitis occurred in this 25-year-old
wom an w h o noted blurred vision as she was recovering from
an uppur respiratory infedion. Her visual acuity wan 20/40,
right eye and 2 0 /2 5 , left eye. 5he had viJreous cells, sheath­
ing of the relinal veinsr and mild optic disc edema bilaterally
(Ё and F 5 h e was treated w ilh 30 mg d a ily o f prednisone
□rally. Two weeks laler her visuaE acuHy was finger count­
ing п I i fool iSOcm), righl eye, and at 5 feel fl.SOm:-, Ic*fl
eye. 5he had severe hem onhagic retinopathy that was more
marked in the right eye ( t —IJ. Angiography (J—1_> showed
marked closure of the peripheral retinal vasculature, ih e
suhsoquendy d A c jq o e d Stvere; pro3iferiJlivLh retinopathy that
required bann^Srtal pholocttaguJalion and vitrectomy.
Acute Retinal Periphlebitis and
Par uveitis Associated With ViraMike
Upper Respiratory Disease
Acute bilateral visual blurring associated with inflamma­
tory cellular infilLration of the anterior and posterior ocu­
lar chambers and fluorescein angiographic evidence of
periphlebitis may occur in some patients during or imme­
diately following, an upper respirator}1 or flulike illness
(figure i 1.01A-1 5 N Visual blurring usually disap­
pears in !-2 weeks in association wilh return of the fun­
dus and angiographic findings to normal. An adenovirus
was cultured from the stool of one such patient (E'igure
11.01 A-D}.
Idiopathic Frosted-Branch Angiitis
Pattents with idiopathic frosted-branch angiitis pres­
ent with visual symptoms associated with a siriking oph­
thalmoscopic picture in оде or both eyes of Widespread
prominent perivascular infiltration that in most patients is
confined lo the major rettnai veins {Figures LI.01 li—L and
LI .02Л—J-).'1 About one-lhird report a Пи tike illness as a
prodrome. Visual loss can be severe, to include macular or
peripheral exudative retinal detachment [E'Lgure S!.L12A, С
and D). The disorder is more common amongst Japanese
individuals children are more often affected
than adults, though age distribution ranges from 2 to 42
years.18 frosted-branch angiitis responds to systemic ste­
roids Very often, though several cases have been known
to resolve without treatment. Secondary causes have to be
ruled out prior to starting steroids. The disease burns oul
over weeks to months. Although Lhe visual prognosis is
generally good, some patients may develop retinal vein or
artery occlusion, extensive retinal vascular closure, retinitis
proliferans, vitreous hemorrhage, and rubeosls of the iris,
macular epiretina! membrane, macular scarring, diffuse
retinal fibrosis, retinal tear, oplic atrophy, peripheral atro­
phic retinal lesions, ,md severe perivascular hemorrhages
(E'Lgure ILOIG-E.). Ihese latter patients become indistin­
guishable from patients wilh acute multifocal hemorrhagic
retinal vasculitis (see following discussion).
Secondary Frosted-В ranch Angiitis
I'rosted-branch angiitis can be a feature of several retinal
diseases, including cytomegalovirus retinitis, lie heel's dis­
ease, Lupus erythematosus (figure 11.02G to ]), lipslein-
liarr virus retinitis, syphilis, toxoplasmosis, herpetic
retinitis, human immunodeficiency virus (] IIV) positivity,
Hodgkin's disease, rapidly progressive glomerulonephritis,
staphylococcal and streptococcal endophthalmitis.1l' 2'
Acute Multifocal Hemorrhagic Retinal
Vasculitis
Otherwise healthy patients with acute multifocal hem­
orrhagic retinal vasculitis develop Loss of vision asso­
ciated with mild anterior uveitis, multifocal areas of
retinal vasculitis (predominantly venular) with marked
intraretinal hemorrhage, retinal capillary nonperfusion.
M .02 Frosted-branch angiitis.
A-F: A 9-year-otd b o y lost v is io n p a in le ssly in b o th eyes
Lo (h e Ьллс1 m o tio n s lew d o v e r -1 days. H e b,id 34- tiefls In
both a n terio r chamEierF- w ilh fane kora tic p recip itates. B o lli
retina show ed w id e s p re a d tnjHtt^d-hranch angiitis in v o lv ­
ing t № arle rie s a n d ve in s, a h d l.irge in te rio r Ix u d a liv E retinal
d etach m e n ts (A —C l. t h e vessels s h tjw e d m ild lea k a g e from the
in v o lv e d vessels |D ). H e was- afeb rile. S y s te m ic w o rk u p for
c o lla g e n v a s c u la r disease, sarco id , tub ercu losis, p e ri- n u cle ar
^nline-Lilioph:! c y tc p la s m k : a n li с lin e a l am i n eu tro ­
p hil CTtote^UsiTiic an tib o d ies, c e m p lr f e b lo o d c o u n l, renal
fu n ctio n , a n d chest V-ray w a s all neg ative. H is w h ite courrl
w as s iig b lly e le va ted Lo 12 HOD c e l ls/ml. H e re c e iv e d in tra­
V En ous m e lb yl p re d n iso n e lisr 5 days io l lo w e d b y oral ste­
roids. Tbe v is io n b eg an to im p ro v e s u b je c tiv e ly a lte r 2 days^
an d Lo c o u n t flrtgere by 4 days. The e x u d a tive re lin a ! d e ta c h ­
m ent re so lv e d Ljy d ay 8. B y w e e k 5, the p e riv a s c u la r infiltrates
h a d d is a p p e a re d in tE>e right e y e a n d w e r e p iu se n l o v e r s o m e
o f Ih e smaEI vessels in Lbe left e y e JE a n d F:. O v e r Ihte nexl &
m o n lh s b it v is io n y ra d u a lly returned to 4Й5ГЗ an d 2EV20 w ilb
e v e n tu a l c le a rin g o f all p e riva sc u la r infiltrate. ivtild p ig m en t
m o ttlin g re m a in e d in Lhe m a c u la .
3}ег1arteriolar plaques associated wilh systemic lupus
erythematosus.
G —|: T h is 4 1 -year-old w o m a n h a d 20/20 a n d 20/25 v is io n
tn e a c h e y e . A t a g e 14 sh e w a s d ra g n o se d w ilh ju v e n ile
rh e u m a to id s j t h r i l l rind Still's d isease. S in c e Lherc a d ia g n o ­
sis o f sysLem k lu p u s erylL u 'm .n o s u s w ilh im m u n e h e p a Litis,
n e p h ro p ath y, p le u ro p e ric a rd iL is , a b d o m in a l serosilis, s p le n ic
arteritis, an d p a n c r e a tic v a s c u la r le s io n w a s m a d e . O c c E u s iv e
vas c u lo p a tE iy w ith m u lLrple-b rancb re tin al a rte ry occEusions^
n e o v a s c u la r iz a tio n o J Lhe d is c a n d retin a w ilh re c u rre n t v it ­
reous h e m o rrh a g e s re q u irin g s catte r laser, v itre c to m y , a n d
c a ta ra c t su rg ery w a s m a n a g e d . T h e p e ria rte ria l w h ite p la q u e s
w e r e noLud in 2002 ( C a n d : a n d re m a in e d u n c h a n g e d U ntil
h e r last e v a lu a lio n 4 yeare I л Lei ■H an d J .
[A—F, ci iurlLjiy « f L)i. l-VlLjr 5офЫп; I, (murlL'iy иГ U r [YliL.hud
CjL>t[lthlLirn..
retinal neovascularization. oplic disc swelling, and vilri(is.J
Ketinal necrosis is not a prominent pari of this syndrome.
Oral prednisone appears to be of some benefit in treat-
menL of this disorder, which is unresponsive to treatment
wilh acyclovir. f:holocoagulation of the neovascular com­
plications may be necessary. The etiology of this disorder,
which shares some features with Ueheel's disease, Eiales'
disease, and acute retinal necrosis, is unknown.
RETINOCHOROIDAL
DEGENERATION ASSOCIATED
WITH PROGRESSIVE IRIS
NECROSIS
Margo et aL described progressive pigment epithelial and
retinal atrophy that began in ihe macula and juxtapapil-
Eaiy retina [E-'igure U.03A-D, M, E, h, L and N], mild iri­
tis... elevated inlraocular pressure, severe pain, progressive
iris atrophy (Figure 11.03E^ and Jj, progressive decrease
in electroretinography amplitudes, and complete blind­
ness within 3 years in a healthy 34-year-old man whose
extensive medical workup Was negative.54 Eiistopathology
revealed pigment granules and pigment-laden macro­
phages in the anterior chamber, severe ischemic necrosis
of the iris (Kigure 11.Git-'), chronic inflammatory cells in
the uveal tract, and marked chorioretinal atrophy, with
only a thin strand of glial tissue resting on an atrophic
choroid. There were patchy areas of preservation of the
inner retina posteriorly (E'igure II.03C:] and some pres­
ervation of the retina and choroid peripherally, where
thrombi were found in some of the choroidaE blood ves­
sels. tlectnon microscopy revealed no viral particles or evi­
dence of a storage disease. The authors found no cEues as
to the pathogenesis of the disorder. A similar patient was
seen by EJr. JampoE (Figure 1 Н Ш Е-0 ). Note the deep
trench like chorio retina! atrophy on the angiogram (Jigure
1H13M and OJ.
I ■.03 Retinochoroidal degeneration associated with
progressive iris necrosis,
A—C : This Нел 11hy 3-J-year-ukl man became bilnlerally blind
within 3 years- m the onset (if -an unusual r-etjnotftnfoidal
degenefnlive disease. W illi in 3 months of [he onset of symp­
toms his visual acuity declined to 20/300. There was severe
mottling (if the retinal pifjinorU epitheliLmi in the macula bilat­
erally iA and Si. p ark adaptation s,tudiesr visual evoked poten­
tials, and eJectroretinofyam wtRe normal, liyhtoen monlhs
I.Her lEtltl- w hs extensive degeneration of ihe relina, counting
fingers visual acuity, and severe ocular pain bilaterally (C and
D>. The third year of his illness was characterized by severe
retinal vascular narrowing, mild iritis, progressive Fris atrophy
iLi, modest elevation o1 ihe intraocular pressure, and blind-
rteSSb Both eyes were enucleated because of severe pain.
H^ppatEidloglc examination revealed severe ischemic necro­
sis of ihe irit IFI, mild nongranuEomalous uveitis, and marked
c h o t iO r d M atrtjphy and degeneration poslecjuaLoriaJly. There
were a le w areas o f preservation of the inner retina posteriorly
[Cl'. Llectron microscopy revealed no viral panicles.
H - O : Ihiii male was first seen elsewhere in- 2004 with vileJ-
liforn-- lesions in both eyes and vision of count, finders in Ekti I:
eyes (Й and к l-lis visual fields were constricted and electro-
retino^ram revealed decreased rod and cone l-unation in Ejo IEt
eyes. In M ay 2005 he developed bilateral uveitis fur ttie first
time. Uveitis workup was negatrve for human leukocyte anti­
gen fHLAl B27, fluorescent treponemal antibody ahsorplion,
Lyme, human immunodeficiency virusr angiotensin-converting
enzyme, complete Eilood count, rheumaLoid factor, an Li nuclear
antibody, and erythrocyte sedimentation rate. He suffered sev­
eral Episodes of uveitis that were IreaLed elsewhere and was
known to develop steroFd-induced glaucoma. By 200b fie had
developed iris atrophy and atrophic lesions in both macula.
He was first examined Eiy Ur. Janipol in April 2008 with fur-
tEier decrease in vision in the nghl eye, wEren both irises were
necrotic (J) and Esoth macula showed widespread chorioreti­
nal atrophy tК and I. . Lxlensive ch<Kiocapi]3arjs and choroi­
dal atrophy was seen on angitjgraphy IMi. The Tighl eye had
a cloudy cornea and traction retinal detachment. A par* plana
vitrectomy, membrane peel, and retinal detachment repair
w ilh silicone oil placemen! in the righl eye did no1 improve
his vision. Vitreous and retinal samples showed mixed inflam­
matory infill rate anti were negative for varicella-ios-ler, heTpei
simplex, cytomegalovirus, and Ep&tein-Ban virus. The macula
was verv thin on optical coherence tomography imaging. A
year Eater IEh inflam m ation slabiliied w ith a clear media and
extensive atrophic chorioretinal scar (N and O ). The clinical
features are similar to the case reported by Curtis Margo.
[A - О , In y ir i M .ir ^ u c t л !, t . '1 1 4 < J O A r r i r r i c i m 1
M l (h e . 1A iib t lljt f r ir t . A ll
rij^llb- rt b-LrVmJ. H-(J. LHJUrtL".V tjl LIf. I CL' l,bn!-J>Lil..l
ACUTE POSTERIOR MULTIFOCAL
PLACOID PIGMENT
EPITHELIGPATHY
APM PPE typically affects young healthy male or female
palients [average age approximately 25 years), who
develop rapid Lcjss-of vision in one or both eyes second­
ary to mu Ilip le postequatorial, circumscribed, flat, gray-
white, subretinal lesions involving the retinal pigment
epilhelimn (RPEi] (Figures tl .04-13.Об).'"''
Eesions are rare]}1 associated with clinically apparent
retinal deLachmenl or with retinal hemorrhage (figure
11.05H and С].-'" '[he overlying retina usually appears
normal. Inflammatory cells in the vitreous may be pres­
ent in 504-k of patients. Approximately one-third of
patients give a history of a flu like syndrome antedating
E I .e)-I Acute posterior multifocal p la со id pigment
epitheliopathy [APMPPE),
A -F: This hen I liny 22-year-o3d wom an developed blurted
vision ir bo<h eyes 5 days before admission. Her past history
was unremarkable. Visual acuity in lhe right eye was 2tV200
and in the lefl eye was 20-'2i>. Note.1 the multifocal, ftal, white
I s if lf ii involving the retinal pigment epithelium (RPbJ iA).
Tfu1 lesion superiorly had Utidercone partial rusokilion. .^nd
some detail ы of ih e under lying choroid were visible. Note
absence ol serous detachment Ы trie overlying relina. ta d y
angiograms revealed absence of Fhackground fluorescence ir>
'these
lhe region of lhe active lesions (Б). Some Fwckground lluo-
nesce№e is visible in the partly resolved lesion -superiorly.
O ne hour afLer injection, lhe angiogram showed fluorescein
staining ol all lesions (Cl. N in e days later, her visual acuity
had returned to 20/50. There was fbcat depigrnenLation of
lhe ЛРЁ following lhe rapid resolution of Ihe placoid lesions
in both eyes [D and El. Seven man lbs later, visual acuity was

the onset of visual symptoms."30,* [n цпе CJbe
Et followed a mild hypersensitivity reaction to swine flu
vaccine" and varicella-zoster vaccination in another."1
А РМ РРЁ has occurred in patients with thyroiditis/1"' cere-
brovasculitis,^"1'' adenovirus type 5 infection,31'
lym phadenopatby,hepatom egaly {Figure 11.04К and
L},M erythema nodosum,1' 011 regional enteritis,^' sar-
cotdosis,('|i'h" acute nephritis/'" lupus erythematosus, 1
serologic evidence of E.yme disease,'"" s Wegener's granu­
lomatosis,' 1 systemic necrotizing vasculitis. ' ulcerative
colitis, " and spinal fluid pleocytosis and elevated pro­
tein. 3й,3? I J 1Чо patients with evidence of cenlral ner­
vous system (CN5) srascu litis died within several weeks of
onset of A PM PPE as systemic corticosteroids were being
tapered.1" ■'' Autopsy in one case revealed evidence of
granulomatous arteritis in the leptomeninges." 'Ihese
cases suggest that AE].\1PPH may he lhe initial manifesta­
tion of primary CNS angiitis, which is associated with
a high mortality rate of approximately 9 5 if untreated,
46% if treated with corticosteroids, and S°b af treated with
corticosteroids and cytotoxic agents.'*
Other ocular findings include perivenous exudation
in the r e t i n a . p e r i c h o r o i d a l venous infiltration,'"1 and
dilation and tortuosity of the retinal veins, papilledema,'1''
papillitis, oplic neuritisr4^ ,3-JJ',!i3-': episcleritis {Figure
11.05A),1" iridocyclitis, and central retinal vein occlu­
sion [Dr. Lawrence A. Yannuzzi, personal communica­
tion] 'Jhis latter may develop as a resuh of vasculitis and
swelling within the optic nerve.
Infrequently, АРМ РРЁ occurs uni laterally, lhe second
eye is usually involved within a few days or weeks after
the first. !n 2 palienLs the interval was .50 and 36 months
(t-'igure 13.04CJ —I). " Recurrences are infrequent and usu­
ally occur in the first 6 months following the onse( of
symptoms (Figure 11.04A-F). Characteristic features of
the disease are the rapid resolution of the fundus lesions
20/20. Thirteen mo nibs after lhe onsel of her disease she had
recurrence ot" symptoms in lhe left eve with transient Joss of
vision. These Eesions healed, and w hen last seen -10 months
a Her the onset of her disease, visual acuily was 2Q/20. Note
evidence ol lhe m ore recenl lesion superiorly (F .
G-h This A5-year-old w om an developed rapid loss ol vision
(1CV2001 in lhe lefl eye. Mote the large centrally located
fesion (C). Angiography revealed other lesions, aEt of w hich
were non I luorescenl in lhe early phases of angiography (H'
and which staintfd (atj^r 111. Twelve months Jater. her vision
had returned lo 2tV20 iJ). ThirLy months after Lhe onset of her
disease she developed a simiEar large central lesion in lhe
right eye and esperienced an identical clin ical course tn lhal
eye.
К anti L: Severe bilaleral A l'M P P t in a 15-year-old wom an
who noted the onse4 ol visual loss several days after an upper
respiratory infection. Mote tbe evid en ce of early resolution
□t lbe macular lesion ГЮ. Vilreous cells wore present, The
patient's visual acuity was 20/200. A liver scan revealed hep­
atomegaly and abnormal uptake of radioisoK?pt!* in the left
tobe. H e r electro-oculographic Ttnding^- w ere normal. Her
electro-retinographic findings wore s’jb n ojm aJ. Si\ munths
1а1и lbe visual acuily was 20/50 in lhe right eye and 20/25
in the lofL LTt!, {Jt.'spiCe Lhe widespread alterations in the KF’t
IhftHi^hout the posterior pole of bolb eytts (Lj.
LA—f , frLim ( J a s x . > 1> 6 H. A niL-ric.in iVUvJit ii] A ^ u c .M t io n . A il ris^Mb.
rLscr^i«r.J
and the delayed remarkable return of visual function, usu­
ally to lhe level of approximately 20/30 or heller ( I'igure
11.04 A- D ).39 Within a few days of the onset of symp­
toms the acute gray-white lesions begin to fade centrally.
Within 7-12 days they are completely replaced by areas of
partly depigmenled ftPE (Ngure U .IMD and hj. Irregular
clumping of pigment occurs and day-to-day changes in its
pattern develop over a period of mouths. Ihe acute and
subacLile lesions superficially resemble those seen after
pholocoagu lation.
 During the acute phase of AFMPPH the subretinal
Eesions black out most оГ Lhe background choroidal fluo­
rescence (['inures 1] .041^ and 1L, ]].05Cr and U.06D).
Mid- and late-phase angiograms demonstrate diffuse, even
staining of the acute lesions (Figures 11.04E5, С, 11.. and I,
and i 1.0 6Ei). During the course of early resolution of these
Lesions, angiography demonstrates large choroidal ves­
sels coursing through the center of the partly faded gray
Eesions before the development of staining in Lhe laler
pictures (figure 1I.04KJ. During the later course of reso­
lution, angiography demonstrates extensive alterations in
the background choroidal fluorescence caused by changes
in the content of the RPE but shows relatively little evi­
dence of occlusion of the choriocapillaris. Indocyanine
green (IC G ) angiography shows dark spots (figure U.OoE.)
correspond]Ltg to Lhe placoid lesions and these do not
stain late, unlike fluorescein.1 ^ 'Jhe lesions appear Lo
involve the KE>Ei and (he adfacent photoreceptors on opti­
cal coherence tomography (OCJ)., which shows disruption
of these structures during the active phase and recovery
when the Lesions heal. Very occasionally, shallow sub-
retinal fluid has been seen overlying the placoid lesions
on OCE'; exudative retinal deLachment is not the norm in
AEWiETL Microperimetry can demonstrate ihe involved
areas and recovery of function in those areas once the
lesions heal.14' Subnormal electro-oculographic Findings
have been reported during the acute stage of the disease.
Most patients tested during the acute phases of the disease
have normal electro-oculograms and electro re Linograms
(LRGs). One patient with severe involvement had normal
electro-oculographic findings with subnormal cone and
rod eEectroretinographic findings (figure ]] .04К acid ].).
ТЪв prognosis for visual recovery is good. Visual recovery
can occur up to as long as 6 ntonlhs. In an average follow-
up of over 5 years in 30 paliettLs seen at the llascom Palmer
fye Institute, all but two eyes had 20/3О or belter visual
acuity at the last examination.v' Many patients will identify
small residua] paracentral scotomata when carefully tesLed.
Recurrences and the development of choroidal neovascular­
ization occur infrequently (figure I] .05D and Е ) зя* °^ йз
Hue cause of this disease, which in many instances
b assoc i::.Led with cad au i: of svslemic involvement, is
unknown. In the eye it appears to be an acute, self-limited
disease- initially causing multifocal areas of color change
in the RPfc and perhaps retinal receptor cells, lh e cell cyto­
plasm apparently becomes sufficiently cloudy that it blocks
out alt background choroidal fluorescence. 'Jhe course and
nature of the disease suggest the possibility of viral infec­
tion. figure 11.05 IK—ij illustrates schematically some of
the presumed anatomic changes in this disease. Despite the
extensive alterations in the pigment content, the RPfc ceils
and most of the retinal recepLors apparently recover and
I 05 Acute posterior multifocal placoid pigment
epitheliopathy {АРМрРЁ).
A: Episcleritis in a patient presenting w ith h ilateral APM FPLi.
В and (.' А Н М Р Р Ё assoLiated w ilh а small subrLHinal hemor­
rhage (anuW).
D and E: Choroidal neovascularization (arrows.; occurring
sc^tetjl years after Lhe palicnl recovered near-normal visual
acuity Lifter bilateral $Р/у}РРЁ
F —I: Schematic diagrams depicting probable histopatho­
logic changes and ftuorescein staining pattern in A P M P F E .
The acute ye! low-white fucal Iasi on is probably com posed
of swollen reLinaJ pigment rjpilhelial (RPL.i cells and dam­
aged outer reLinal segmonls beLwoen Lhe ariow s in F--H. In
the early-phase angiograms the fluorescein фЕаск sLipplingf
has perfused the choroidal circulation i'Fj, and quickly stains
Lne chqfOid Iс h:, and is Iwginning to movch into the base of
Lne swollen KI-’E colls w ilh cloudy cytoplasm i C l Loss of
transparency of lhe К F t and outer n=1inal гясерЮгн total Jy
obscures Lhe fluorescein in the choroid. In the late stage of
angiography lH> the dvE-f hat stainud the alfeded cells, С1ю-
roid (chf, and scEera (5), causing the acute lesion Lo appear
hyfierfluomscenl. Healod slagu of A P M P F E , late phase of
an^tpgraphy flj shows restoration of Llie ouler retinal-blood
barrier, palchv areas of depigjnentation and hyfierpigmerHa-
lion of Lhe Kt'b cells, and regrowLh of lhe rrjlinal ouler seg­
ments. but sDme loss of receptor cells.
visual acuity usually returns to near normal, lhe end-stage
of this disease is similar in this respect to rubella.
Manv authors have favored choriocapillaris occlusioti
as Lhe cause of Lhe color change in the R P f and the early
angiographic rnidlngp^'35'46^ ^ 6^ 5 ihe following are
difficult, however, to explain on the basis of choroidal vas­
cular occlusion: (1) the variability in the size and shape
of the lesions, which appear to have no relationship to
the anatomy of the choriocapilEarisj [2] the Failure of ihe
acute lesions to slain with lluorescein from ihe periphery
inward, as would t>e expected to occur from neighboring
normally perfused choriocapillaris; and (3) (he frequency
of recovery of visual function.5^ Demonstration of targe
flu-orescent choroidal vessels coursing through the area of
partly resolved acute lesions (figure L1.04K) does not nec­
essarily mean there is nonperfusion of the choriocapillaris
in these areas. Jhe RHE: cells, which undoubtedly are still
preseiit in these areas, may be sufficiently opaque l.o atten­
uate ihe fluorescence arising front Lhe choriocapillaris but
not Lhat in the targe choroidal vessels, the findings with
ICG angiography are similar to that wilh fluorescein and
in the author's opinion do not shed further light on the
pathophysiology of А РМ РрЕЛ 1
W olf et al. reported HLA-ЕГ? antigens in 40% and
JEEA-DR2 antigens in 57% of patients with AP.MPPli ver­
sus 17% and 28%, respectively, in controls.^
Lpntm-
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 There is no information Concerning lhe relative value
of systemic treatment with corticosteroids compared lo no
treatment of patients with APM PPE. 'I he natural course of
the disease suggests lhal the visual prognosis is favorable
without treatment, Some might argue that corticosteroids
should be given, if /or no other reason than Lo reduce the
potential of C \ S complications it is unknown, however-
whether this treatment is beneficial or harmful in this
regard. Patients and their families should be alerted Lo
the relatively low possibility of CNS complications and of
the importance of promptly reporting any symptoms or
signs suggesting CMS involvement Ihere is evidence lhal
patients with idiopathic CNS angiitis benefit from cortico­
steroid and cytotoxic therapy."'
It is important lo differentiate A PM PPE from serpigi­
nous (geographic) choroiditis. Although the acute lesions
in both diseases appear similar ophthaLmoscopicalLy and
angiograph Leal Ly, the lesions of serpiginous choroiditis
resolve more slowly and Leave in I heir wake ophthalmo­
scopic and angiographic evidence of marked atrophy of
the undeilving choiiocnipil laris and larger choroidal ves­
sels (see pp. 362-964]. Some patienls reported as hav­
ing APM PPE with atypical features, such as branch vein
occlusion, may have had serpiginous choroiditis4^ '
Serpiginous choroiditis is a chronic, recurring oflen severe
disease that may leave lhe patient with severe visual dis­
ability in one or both eyes. Table 11.1 outlines some of the
important differences in these m o diseases.
lhe mtilLifocal white lesions in APM PPE musl be dif­
ferentiated from other causes of multifocal deep retinitis
(e.g., diffuse unilateral suhacute neuroretinitis) (see Ngure
Ю.29А-С), multiple evanescent white-dot syndrome
(M EW D S) (Figures 1I.15 and focal inflammatory
cell infiltrates of the choroid (e.g., multifocal choroiditis
wilh pan uveitis (M CPJ, pseudo-presumed ocular histo­
plasmosis syndrome (POEIS)), sarcoidosis/'^11 secondary
syp hil is (E'igures Ю.07В and .G, IQ. ЗОН, and IQ.lllJ, dif­
fuse choroidal infiltration in Harada's disease that may be
associated with multifocal ill-defined lesions at (he level of
the pigment epithelium (see figure ]].26A).:il' sympathetic
uveitis (see Figure 11.29Dj, multifocal zones of occlusion of
Table 11.1 Uiriirn.fiEi.il djii^nu-blHL Iг:;Иlirljt uf Jiuf-L- p:№l?riur rnultifuiul pJmjLHd ркч|jiriс:пI Lpithcdiufjiithry -IAPM I-1РЬ.I j n J s^rpi^.jm.njt- c/huruidit^
^edonffll
feanafed ^Temic
V'iLUL: j :'iL-Jl
Acutateims
1лйя1ddlSluSin
Lpehi-eJi^
ОписИ лЛсрт;
fVjiumlre alr«lri иагтд
V::iiL>№cc№'
EtCJ’HCE
С5кшФ1 necraacuk'ialjof
E- Gt Acute posterior multifocal pla со id pigment
epitheliopathy,
A—1: 1his 17-year-old Сли :.л sian m,ile presented w ilh a b-day
history of {kfcrrrased vision in Both eyes. H e had had л low-
grade fe w r Lind malaise 1 woe-fc befbre I he? onset of 'visual
symptoms-. Visual acuity was 20/200 in both eyes. TEm* right
eye showed several pf^cQid yrav-white lotions in trie jjosle-
rior pole, and Ihe? midperiphery o f holh eyes. {A - Q . A fluo­
rescein angiogram showed early hypotluorescence ol the
active lesions and I ale diffuse hypedl ucrescence consistent
with a diagnosis, erf acule posterior pEacoid pigment epi-
theEiopalhy I.D and Et. His visual acuity 2 weeks later was
20/400 tn both eyes. The acute lesions Eiad faded with sig­
nificant pigmcml mottling ( f and £■ . Six monllis afler onsel,
visual acuily improved lo 2(VbO in ihe li^hl and 2Q/.S0 on
the left, w ilh extensive hyperpigmentafy response. Two yeare
later visual acuily w as 2Q/30 on the righl and 2(У300 on the
Eeft w ith no active lesions. He developed a choroidaE neo-
V£jjt[jla> membrane (H and Г, arrowi'i ii: the lefl eyft whit h
was Ireated w ilh phflflddynamic Lhtimpy, and the visual iitu-
ity improved to 20/60:
)-L: This patienl wilh bilateral mu Hi focal placoid lesions
□I acute posterior mull ifocal placoid pigment epilhelio-
pallTV (J anti K: shows choroidal попрргЕЦраоп on indocyaninc-
green ii;.
IA-I, cuurk'sy 1 if t Jr. Crtt I Inil.:; 1-L. crjurlusy n! Ur J-’i i.h-.irrE Sp.iichi.:
Lhe choriocapi Haris [e.g., toxemia of pregnancy; see figure
3,!>yD). primary or metastatic neoplastic infiltrates of Lhe
choroid or suh-EiPEi space (see figures 13.31G and El and
14.31 D and E), and multifocal areas of deplgmenlation of
lbe choroid, such as occurs in vililigjnous (birdshot} cho­
rioretinitis (see E'igure 1S.45A and 3i). Focal liuraoimatbr^
cell infiltrates of the choroid are ofLen smaller and slightly
elevated, frequently persist for several weeks or more, and
often cause secondary detachment of the overlying retina.
'Jhey may completely resolve without leaving significant
changes in Lhe overlying RP1\, or they may cause varying
degrees of atrophy of the choroid and RPtL Lhe aulhor
believes thal the patients reported as having relinal detach­
ment secondary lo APM PPE showed features more typical
of a diffuse underlying choroiditis, probably Harada's dis­
ease, rather than AE’ME’Pli (see figure и.26А ).ч-^г
APM^Ft ^rpb^nu-Lib cbiiniidiLis
»:crt J4: Hiid Цертиh'u iteuE
.(hjerrapalorf rluctia:,er^tieinanoJobn Hub
'воогаииЫк.НЕяНЛ^ !i:. J -::d^Li-l^
fliatErai U'ElaJirj ш^1оЛем
HaT. g'jf-wilE.relna.pare-Teprltiial bebt^ Зите
^Istuaflonai Иег|1^Ьг/
.У-LiEf iOtilLd UnjE^'iixkr-LUE
Ф;
MniTiL
liHB hieqjerl
HCEfedl Рои
t>p:uJ
^i y :J.i :L i' E.Ji-mi!:
 ]Ъе syndrome of acute retinal pigment epitheJLHLs is
characterized by the development оГ cEuslers of smalE pLa­
ment spots surrounded by halos of depigmentation Ln
young patients with a recent history of visual loss. 'Lliese
patients experience rapid recovery of vis Lori [see p. У74).
In general, however, the lesions in APM PPE are much
Earger than can be accounted for on the basis of the H P i :
findings in acute relinal pigment epitheliitis.
Extensive pigmentary changes remidning during the Late
stages of ЛРМРРЕ (J:igure IE 04EJ may be mistaken for а
widespread tapetoretinal dystrophy. Lhe clinical history
of rapid Loss and recovery of vision, the normal-appearing
retina] vessels and optic nerve head, and usually normal
electrophysiologic findings should differentiate relinal dys­
trophies from the late slages of APM PPE.
Prituck and associates have demonstrated the pres­
ence of urinary casts in 3 patients during the active phase
of APM PPE.50 The significance of this observation Is
unknown.
Although most patients with APM PPE present with
multiple one-disc diameler-siwe white lesions randomly
scattered in (he posterior fundus, the size, shape, and dis­
tribution of the Lesions nr ay be variable (Figure U.Q4C).
In some cases the lesions are smalt, are confluent, and may
show some persistence of non fluoresce nee into the 3ale
stage of angiography, in several of these cases the Eesions
were uniformly small and closely spaced, similar to those
which occurred in a 35-year-old man described as having
diffuse punctate pigment epi the!Lop athy by lillnder et aL 6
] heir patient failed to recover central vision. More recently,
Jaich and Johnson' analyzed 6 older patients ranging from
5S to S2 уелть of age (average age 72.5) with a few placoid
Eesions in the macula, who had several features differing
from APM I’PH: older age group, lesions mostly confined lo
the macula, late fluorescein showing patchy hyperfluores-
cenee unlike the even staining pf.APMPPEr recurrences, late
geographic atrophy, poor visual recovery and choroidal neo­
vascularization in a significant number of them. Ihis group
is best considered a separate entity at this time. Description
of additional cases Ln the future and expansion of the spec­
trum may help understand their pathogenesis. I'wo other
conditions that resemble APM № 6 in certain aspects are
persistent placoid maculopathy and relentless placoid cho­
roidopathy, described next.
PERSISTENT PLACOID
MACULOPATHY
In 200b, 6 patients with bilateral macular placoid teslons
superficially resembling macular serpiginous choroidopathy
l I .и" Persistent placoid maculopalhy (pigment
epitheliopathy},
Л - H : Tbi н 5У-уопг-оЫ previously pfealthy male brVsf^ited
w ilh ,2Q-'4i> ariftU 2Q/.'tO vision. Placoid yellow lesions weft;
prraenl in lhe tfrtacula bilaterally. The lesion remained hypo-
fluoreacenl and iLained miJdly verv Ia1e in lhe angiogram. A
classic m i l l choroidal neovascular membrane wau present
ju\La fovea lly. J-lu Lindefwent № d(xlyti|tri^C iherapy and the?
lesion involuted. Iju I it relum ed much laigEif .1 month!; laler
(H) and was resisilLT.n1 It) treatTm'nl.
1—t : This 60-year-old male developed a placoid les-ron in
the rij'ht macula that 50on developed йИоёпЙй of choroi­
dal neovascularization and subrstinal hemorrhage (I and J;.
Anijkjgram showed per.^ialenl iivpofluoresconce and late
mild patch® hyperlluorebcence typing of persislenl placoid
pigment epitheliopiHlhy, accep) for Lhe early lacy hyperfluo-
mscent e o f the <homjdai neovascUpif! niumfjrane (K and Lj.
IXlourtesy с>Г Dr. L.iwrencjL' V jn n u z f L H , Akt>, Y jn n u jz l L n w m x v J., 1he
R e t i n n ! A l l , i s . S i H j n r l c i r s 2 0 1 t l r ^ r B - U . 7 0 L f G- 1 Г2 № , р _2 Ш
followed variably up lo 20 years were described from five
centers.40 They were in their sixth lo seventh decade, had
bi late ml involvement. the while macular lesions persisted
for several months to years before fading, and they showed
a propensity to choroidal neavascularizallon, often mul­
tiple, resulting Ln disciform scars In spite of foveai involve­
ment and persistent lesions. Lhe visual acuity remains good
till choroidal neovascularization develops. On fluorescein
angiography the Lesions remain non- or hypofluorescent
LiII late and show minimal fluorescence in the tale frames
(E-'igure L1.07J. Several small choroidal neavascuLar mem­
branes (CNV.VIs) are seen. On ICC angiography Lhe Lesions
appear non fluorescent throughout the study. No evidence
of vitritis or anterior-chamber inflammation has been seen.
"I"he relatively good vision (unless complicated by CNVM )
argues against persistent choriocapillary nonperfusion as
the reason for the persistent hypo fluorescence on ICG and
fluorescein angiography. I tie etiology is so far unknown.
Treatment included systemic/'periocutar steroids al some
lime with Improvement in vision. H ie loss of vision is
mainly from choroidal neovascularization.''1,J-'
.* -
RELENTLESS PLACOID I I rOS S e r p ig in o u s c h o r o id itis .

CHOROIDOPATHY
Six patients, aged 17 through 51 years,, exhibiting some
features of A PM PPE and serpiginous choroidopathy
were seen at six different centers from Т9Й4 lo 1997.'"
Ihe acute placoid retinal lesions were multifocal, con­
fluent, or serpiginous Ln nature with initial hypo- and
Late hyperfluorescence on angiography resembling both
A lW IPrii and serpiginous choroidopathy. 'Ihese patients
in addition had numerous posterior and peripheral reti-
na[ lesions predating or occurring simultaneously With
macular involve men l. Older, heal nig pigmented lesions
were often accompanied by the appearance of new aclive
white placoid lesions. AddltidnaUy; all cases demonstrated
prolonged periods of activity with several crops of new
lesions, 50 and some Limes hundreds of them scattered
A—F: This 43-yea r-ofd w om an had a 3-week history erf loss of
cerHral vision i-п Lhe ri^hl eye. Viuual acuiLy counting. fin­
gers in Ibe: ri tj.li I eye and 2CV25 in the Eeff eye. Note the inac­
tive cErorEoreLinal scar surrounding Ihe oplic disc of both eyes
and [he aclive gray lesion a[ the level of Lbe retinal pigment
epiLhelkmi in Ihe Lcimpoial and mfeiior parttops dtf Ihe righl
m acula (airowSj Л.. bnrly attgldjjterbi s i obstruction
of ihe backgroLmd choroidal fIЛЬгеьобпсе in ihe area of Lhe
acute lesion and еагЗу ьLa i n i nfj of Lbe cErerrorelinal scar (L'f.
One-hour angiograms showed sein in g Ml the acute lesion as
well .is Lhe moriOretrnftl -scjr LJl. ie v e n months baler lhttre
was HfflmenEatian in Ihe cenlraJ porLicm of Ihe aclive Зензоп
Iс . Three yr^ars laler Ihere wau formation Ы an adophic cho­
rioretinal scar in Lhe area o f [he previously active lesion fFf.
Visual acLiity In Ihe righl eye wan 2 0 ?2 0 0 .
G - |: A ctive stage erf serpiginous choroiditis |G-|J, Note jig-
saw-puzzle p-iariern of lh e lesions. S^me eye 7 month ь laler
i ]j shows; evidence of additional 1ем о п- ь a l l of w hich are inac­

throughout Lbe futtdus. Growtfii of subacute lesions and tive. Haze iis caused by vitreous cel3s.

the appearance of new lesions continued for 5-24 months К and L: Si mu ILaneons development ol serpiginous choroidt-
Lis iind herpes zoster ophlhalm icus in a (j6-year-old т а л .
after initial examination, and relapses Were common.
Relentless placoid choroidopathy may represent a variant
of seip igl nous choroid i ti s or a new enti ty.'" 1'
One 20-year-old patient has been reported with associ­
ated hyperinlense lesions on magnetic resonance i magi tig It usually begins in the peripapillary area and spreads
in the temporal lobe, found during evaluation of per­ centrifugally over a period of months or years by means of
sistent headache. He received mycophenolate ntofelil Ln recurrent episodes of palchy choroiditis in a serpiginous
addition to steroids and remained stable with resolution or jigsaw рш /le-like distribution outward from the optic
of the brain lesions."1Etiological ly this condition is prob­ disc lo involve the macula and peripheral fundus (I'lgures
ably related to APM RT., but much needs lo be learnt. The 11.08-11.11).
condition has lo be differentiated from A PM EVE, serpigi­
nous choroidopathy serpiginous-like tuberculous choroi­
ditis (see Chapter 10). persistent placoid choroidopathy,
tnullifocal choroiditis, placoid syphilis, sarcoidosis, and
lymphoma.

SERPIGINOUS CHOROIDITIS
(GEOGRAPHIC CHOROIDITIS,
HELICOID PERIPAPILLARY
CHOROIDOPATHY)_______________
Serpiginous choroiditis is an acute and chronic recurrent
multifocal inflammatory disease that appears lo affect pri­
marily the inner ha If of the choroid, the and second­
arily the retina.^-™
 'lhe patient is typically A he^Lthy young or middle-aged
individual when he or she first noLices the rapid onset of
paracentral or ceOtral scotomata In one eye. Ef the center
of the macula is involved, the acuity is often 20/40 or less.
IJio microscopic and ophthalmoscopic examination within
the first seven I weeks after the onset of symptoms reveals
□ well-circumscribed geographic /one of gray-white dis­
coloration of the RPE in the macular area [Figures Ц.0БА
and G, and 11 H I] Serous detachment of the retina is
Infrequently present. Although an occasional patient has
a solitary active lesion in one macula,l<Kj usually the active
lesion is in continuity with a zone of RPL and choroidal
atrophy that extends nasally Lo surround all or a portion
of the optic disc. Inflammatory cell, reaction is present in
the posterior vitreous in approximately one-third of cases
during the active phase of the disease. Examination of the
opposite asymptomatic eye often reveals an area of chorio­
retinal scarring adjacent to the optic disc {Figure П.08В).
Over a period of weeks, the acute gray-white lesions, which
may appear identical to the acute stage of Af\MPPiL, are
partly replaced by mottling and depigmentation of the
REM (Figure 1I.0BA and F). ihe peripheral edge of the
Eeslon often maintains a grayish-white active appearance
for a month or longer (Figures I I .ОБЕ, and H.09CJ. Over a
period of months, varying degrees of atrophy of the under­
lying choroid develop within the discrete zone of previous
activity. Jn some cases the atrophy involves the large as
well as the small choroidal vessels and produces a trench-
Like area of choroidal atrophy [E'igure ll.OflF). In approxi­
mately one-half of patients varying amounLs of gray-white
tissue (fibrous metaplasia of the RPE] develop within
Lhe area of chorioretinal atrophy (Figure ]] Ц А -Gl.
Ih e patient usually develops li permanent dense absolute
scotoma corresponding with most of the Involved areas.
Ih e retinal vessels and oplic nerve head are usually nor­
mal. At intervals varying from weeks to years, the palienL
is subject Lo recurring episodes of activity that each time
Involve a new and usually contiguous area of the fun­
du s. '' " |his process may spread widely into the far
periphery of the fundus in one eye before a similar process
begins in the second eye months or many years later. The
disease frequently involves the macular area, bus in many
cases it skirts the edge of the foveola, leaving the patient
11.09 Serpiginous choroiditis - response to treatment
Ib is 4Е-уеаг-ок1 w tim an was seen fur mild visual distur­
bance in bur left eye o f 4 w eeks' duration associated w ilh
nasal sLut'finest anti congestion in 200?. Her visual acuity
was 20^20 ir mfcb ey&. Lbe lesions w ere inaclive 'A and
and a diagnosis of possit)]e atypical acute posterior mulLi:-
fucal placoid pigment Epitheliopalhy was made. She
relumed in 2007 with changes in her vision and new sco­
toma in her leit eye. The ri^JiL eye remained unchanged,
w hile the leit eye had d eveloped several new lesions t.vilh-
active outer edyes (C)_ The active edges vvefe htraofTLiures-
cenl early and bucairo hyperflutiroHcenl in ihu late s1-tge an
the nn^io^nim : | ■i . 11 ■ ! югчи.игои-- ■
. Ь^члФэрлМп il j ,jnd
Ef. Vi ml liters far varicefla-zaster vims w ere drawn and she
was started on oral prednisone bOmg a day. By 9 days the
iesiorra were 3ess .ictive IF I, Ihe viral li1ers roLurnod low and
яhe was continued on oral steroid thal w l i s tapered over 4
months. W h ile she was o r 1 0 my prednisone, 3 months
Eater she developed new activity al [he nan fovea I edges
(<UV Prednisone was increased lo 4 0 mg and oral mcrfbo-
lre\ate 15 midweek was Started. She responded wiLh no
further recurrences, sLenoids were tapered off in 4 months,
and she remained on nwlEtotrexale foi 1ft months w han
it was Lapened off. The left e v e 2 years IrUer thows inactive
scars w illi geographic edges '.M.T mohl alntiphnc areas show
decreased aufolEuorobcence w ilii fffcreased autofLuorescence
rn lhe healthy adjacent retinal piym enl epithelium il).
with good acuity. Although there is a great tendency for
the lesions to be contiguous, noncontiguous lesions occur
commonly. Some patients w ill show centripetal spread
of the disease.1' ' Ihere is some tendency for concentric
enlargement of the jig^awpuzzle zones of chorioretinal
atrophy to occur over a period of months or yeare. An
important cause of late loss of central vision is the devel­
opment of choroidal neovascularization at the edge of an
old area of chorioretinal atrophy (E'lgure 1] ] IA and ft).)S~
loi, icu.-.os.iio-1n Щ з ОСП1га jn ^ т а л у as 25% of these
patterns. Care must be used to avoid mistaking the gray
exudation associated with subretinal neovascularization
for that caused by a recurrence of an active inflammatory
lesion, likewise,, it is important not Lo mistake a gray active
lesion for a subretinal new-vessel membrane. Fluorescein
angiography is helpful in this regard.
 Unusual findings in patients with serpiginous choroi­ I I . I IJ Atypical presentations o f serpiginous
ditis include local relinal phlebitis, branch vein occlusion c h o r o id itis ,
(E'igure n .]0 );JS EDr L|,:iJL:i optic disc neovascuEarization,1E' A-C: A iliv e Telinilis ,irtd p^JphujjpHSfi and local jarEia ot reLi-
retinal neovascularization [figure M.EOD-K), and a strik­ nilis pro literals | В and С л I Lhu margin of aid л гея
ing predilection in a leu1patients for the choroidal lesions □I branch retinal vein occlusion in patient with serpiginous
to correspond with lhe distribution of tbe major retina] t horoiditis.
veins. One or more sites of focal gray retinitis and overlying D - F rtiilialeral multiple branch retinal vein occlusions in
periphlebitis may be present (figure ELIO). ]hese foci may я 20-year-olri black man with acule loss of vision in boll:
eyes caused by active serpiginous cEwroidilis Ю and E). Six
be associated with evidence of branch venous obstruction
years Liter the palienl had severe bilateral loss of central and
LocalJv or elsewhere in the same or opposite eye (i'igure peripheral vision. КЫи the etfensive scarring ■I-j.
1] ЛОЁ-L]. tJass has seen one patient who because of wide­ G-L: A healthy 23-year-old man presumed with floalefs ir*
spread venous obstruction developed a picture of Ijle s' both eves associated with bilateral scattered active serpigi­
disease with extensive zones of relinal capillary nonperfu­ nous choroiditis lesions, overEy ing and w id ely scattered areas
sion, retinitis proliferans, and vitreous hemorrhage requir­ of rerin-al phlebilis ;CJ, arruwKl, areas of peripheral Capillary
nonperfusion (J and k), F-elinitis prolilerans larrows, F-Ю,
ing pars plana vitFectomy bilLiterally (I'igure lfc'lOG-JJ.
and vitreous hemorrhage iHj. bilateral panrelinal photo-
Although Lhere is a strong predilection for this disease lo
coajjulation and pars plana vitrectomy in the Eefl eye werE
affect (he juxtapapiElary choroid early in lhe course of the required to control Lite proliferative retinopathy. Hive years
disease, in some cases this area is spared until later. afLet bis presenilation his visual acuiLy was 20^15 in bolE:
е у и (L ).
Fluorescein Angiography
ihe acute gray-white lesions appear non fluorescent during
the early phases of angiography and Liter they show evi­
dence of staining that usually begins al the margin of the
choroidr RPt, and retina.^9|01 The history of episodic and
Eesion and spreads centrally (Figure I!. ОSC and D).
permanent loss of segments of the paracentral visual field,
ihe sub acute and chronic lesions show angiographic evi­
the lack of family history, Lhe jigsaw- puzzle pattern of cho­
dence of destruction of tbe choriocapiltaris and IlFE. E'ailure
rioretinal atrophy, the asymmelry of tbe disease, and the
of Ehe atrophic areas to fluoresce during the early stages
frequent presence of marginal gray-while edges of activ­
of angiography is indicative of choriocapillary alrophy.
ity of lhe more peripherally located Eesions are clues lo
As fluorescein dilfuses from the neighboring choriocapil-
the true nature of the disease, 'lhe color and early-pbase
laris, Lhe atrophic lesions show progressive staining from
angiographic appearance of lhe acute lesions resemble
tbe margins centrally. When focal areas of retinal phlebitis
those seen in APM PPE. In this latter disease, however, the
are present, angiography shows evidence of staining of the
shape of the lesions is nip re likely lo be round or oval,
vein wall and may show evidence of branch vein occlu­
their distribution is more likely lo be Fandomty scattered
sion peripheral lo the area of phlebiLis (figure ЙЛОЕ .1Ш
in the posterior fundus, they resolve usually within 7-14
Angiography is useful in detecting and localizing areas of
days, and they leave minimal evidence of choroidal atro­
choroidal as well as relinal neovascularization (figures
phy or loss of visual function. Table ]] ] summarizes the
1] . !0 and 11.11 B). ICC angiography shows dark areas that
differences between these two diseases. Etelentless placoid
correspond to the visible chorioretinal lesions, and some­
choroidopathy is the disease that closely resembles ser­
times larger than them. rlhe hypofluorescence persists even
piginous choroiditis given that recurrences are its feature.
after the acute lesions involute, suggesting continued activ­
Serpiginous choroiditis may simulate any of the diseases
ity in the choroid or persistent cellular infdtraLe lhal blocks
causing peripapillary chorioretinal scarring and neovascu­
IC]C] fluorescence.1" Ihe acute lesion is hypoautofluores-
larization, for example, PO fIS, age related macular degen­
cent wilh a byperautofluorescent edge, tbe subacute lesion
eration. atigioid streaks, drusen of the optic nerve head,
becomes hypeiaulofluorescent and the inactive atrophic
and idiopathic choroidal neovascularization. Clinical and
lesion shows hypoaulofluorescence.1,5 O C f in the subacute
angiographic evidence of juxtapapiElary subretinal neo­
and inactive stage shows thinning of the outer retina and
vascularization is less likely lo be present in patients with
increased backscaltering from the choroidal layers.'1 lhe
serpiginous choroiditis. On the other hand, patients wilh
electro-oculogram and EiKU ate usually normal.
only minimal peripapillary scarring caused by serpiginous
choroiditis may be seen initially with macular detachment
Differential Diagnosis caused by juxlapapillary subretinal neovascularization
When serpiginous choroiditis is advanced in both eyes, before developing any signs of the typical jigsaw pattern of
it has been mistaken for various dystrophies affecting the choroidal involvement.
 An acute lesion in Lhe paracentral region, particularly
in a patient wilh Inactive Eesions elsewhere (figure ll.OSA
anti 15), may t>e mistaken biomicroscoplcally and anglo-
graphically for exudation overlying а CNVM. Likewise a
gray plaque of sub retinal exudation caused hy suhrelina!
neovascularization may be mistaken [or recurrence of the
choroiditis, lhe disease that closely resembles serpiginous
choroiditis in its initial presentation and subsequent course
is tubercular serpignous like choroiditis (see Chapter Id).
When patients wilh a clinical picture of serpiginous choroi­
ditis do not respond promptly Lo oraE steroids or continue
to develop new lesions while on adequate doses of'steroids,
anti if they are from high prevalent countries such as India,
tubercular serplgnous should be suspected. An exaggerated
response to lutjerculin skin testr Wjtth or without evidence
of systcmic tuberculosis, calls for a prompl establishment
of tissue diagnosis of ТВ With PCI? of the vitreous fluid or
needle biopsy of a choroidal lesion.
Pathogenesis and Etiology
The histopathologic findings in 2 patients suggest that
serpiginous choroiditis Is primarily a nongranulomatous
choroiditis (figure I1 .IJC and L'here is no
clue, however, as lo its cause. There Is minimal evidence
that it is part of a systemic d i s e a s e . ' figure I I . OS
(K and I.) demonstrates typical serpiginous chorioidi­
tis that i level oped bilaterally in a pal lent associated with
herpes /osier ophthalmicus. King el aI. found elevated
factor Viii-vun Willebrand factor antigen in Й patients
wilh serpiginous choroiditis and concluded that occlusive
choroidal vascular disease may be Important in Its patho­
genesis.1" Rroekhuyse el aI. found immune reactivity lo
retinal S-antigen in patients with serpiginous choroidi­
tis bul not in patients with A PM PPE.[|S Serplginous-like
choroidopathy is a common manifestation of tubercular
choroiditis.1'1 Given the various infectious or non Infec­
tious association, it Is likely that seiplgnous choroiditis is a
common morphological manifestation to several antigenic
stimulation. 'Though worldwide in distribution, the disor­
der is more common in India.
Treatment
Systemic corticosteroids have proved moderately effective
in serpiginous choroiditis. Their use in those patients with
active lesions threatening the cenler of the macula is advis­
able. kM J he value of other agents, such as chlorambucil,
cycEosporinc A, azathioprine. methotrexate or a combina­
tion of these agents, is unpredictable.12u iiecause of itie
possibility of a viral etiology, Cass treated one patient with
acute loss of central vision in bis second eye with a com­
bination of oral acyclovir and prednisone for 6 weeks. The
results of treatment Ln this patient and four others with
acute serpiginous choroiditis al the liascom E^almer Куе
Institute suggest lhal acyclovir in ay be of some benefit in
M . ET Serpiginous choroiditis causing choroidal
neovasc ula rizat ior .
A a n d E5: N o te the suLirelinal b lo o d (arrcjw, A.i c a u s e d b y a
c h o ro id a l n e (jv a s c u la r m e m b r a n e I a rro w , b l.
C —H i A 1 7 -y e a r -o ld b u y d u rin g a p e r io d cl" 3 3 years d e v e l­
o p e d progressive loss o f ce n tra l a n d pa racentral vis io n in
b o th eyes s e c o n d a ry Iо a ьс-rpi Lj i nous p a tte rn o f sp re ad o f
u io r o i d ilit . Iu x la p a p i i ry subrrrtinal scarring w as present in
trie left e y e in A u g u s t E 9 b 4 :C!l. B y fa n u a iS 19 Ь 5 Ihe lesion
h a d e x te n d e d a n d w as a u o c ia № d w ith s u b re lin a l netyvas-
L'Lplari^alinn a n d blolfld ( D ) . B y N o v e m b e r 1 У Ь7 lh e dise ase
b a d pro g re sse d inLo the т а с и 1 д г area !E I as W ell as in to the
p e rip h e ra l :-.m d u s. N o l e lh e subretEftal scarring la tro w , L- .
E Jtr tu w r: I4 b 'j a n d 19 b 7 a s im ila r pattern o f progre ssive
su b retin a l choroiditis- a n d s ta r rin g o c c u r re d in the rig h t e ye .
N o t e Lhe to n g u e o f s u b re lin a l h b ro v a s c u Iar li^sne la ir o w .
e x te n d in g in lo lhe righL т а t ill a i f a n d C i . Th e p a lie n l Was
k ille d in .1 m oturxryt Iej a c c id e n l s o o n afler Lne p h o to g ra p h s
in t a n d C . H is lo p a lh o ltjri’.ic e l i m i n a t i o n o f ln e ri^hl т л с -
u la I EH!■ re v e a le d e x te n s iv e in filtra h c n o f th e c h o r o id w i lh
ly m p h o c y te s u n d e rly in g a d o u b le layer o f re lin a l p ig jn e n t
e p ith e liu m a n d a Lhrck la y e r o f fib ro v a s c u la r Lissue I ty p e II
su b retin a l n e tJva s c u la riza U u M . N o o rg a n is m s w e re d e m o n ­
strated by e ith e r lig h t o r e le c tro n m ic ro s c o p y .
T r e a t m e n t o f s e r p ig i n o u s c h o r o i d i t i s w i t h p r e d n i s o n e
a n d a c y c lo v ir
I —K : A 3 4 -y e a r-o ld w o m a n Iro m In d ia w it h a 2 -y e a r h is to ry
o f w id e s p re a d s e rp ig in o u s c h o ro id ilis a n d p o o r v is io n o1 2
years' d u ra ! io n in Lne rijqhl e ye pre sented b e c a u s e o f a c u te
vis u a l Eoss in Ihe left e y e . 5iEie w a s ta k in g p re d n is o n e , SO m g
d a ily , Eiy m o u Lh . A c J iv e c h o rio re tin a l lesion s h a d e x te n t Jed
in to the m a c u la o f the left e ye (I a n d J). H e r v is u a l a c u ity
was 2 0 /6 0 . A c y c lo v ir , 4 g d a ily , w a s a d d e d 1 to Ih e p re d n is o n e .
T w o w e e k s later lh e a c u ily d e c lin e d Lo 2 0 / 1 0 0 b u l th e re afte r
im p ro v e d w iLh :n 3 m o n lh s lo 2й -'20 in spile o1 Lhe p resence
o f s u b lo v e a l p ig m e n ta ry scarring (K l.
preserving vision (E:lgure J 1.1If and Kj. Despite the fact
that these patients regained excellent visual acuity after
treat mem, one of Lbe patients continued to develop new
active choroidal lesions peripherally while receiving Lhe
combined treatment. Jlie jury Is still out oil Lhe benefits
of acyclovir. Oral steroid as the initial treatment with addi­
tion of immunosuppressives if the palienl has recurrences
is probably the best strategy al Lhe present time,12' '-6
Photocoagulatlon for active choroidal neovascularization
that does not extend inside the caplllaiyr-free zone is of
value. Intravitreal bevacizumab is useful in those cases
threalenlng the fovea
Prognosis
Good statistics concerning long-term follow-up of this dis­
order are not available. Generally it is a chronic, recurrent
ocular disease thal over a period of many years may cause
severe visual Joss in some patients. Many patients, how­
ever. maintain good central and peripheral function in at
leasl one eye.
ACUTE IDIOPATHIC
MAC ULO PATH Y
Yannuzzi and coworkera reported 9 patients who after a
fin like illness developed sudden severe unilateral cenlral
visual kiss associated with vitreous cells; neurosensory
macular detachment; retinal hemorrhages; an irregular
white, gray, or yellow thickening of lhe RE3h lhal was con-
sintent with a subretinal infiltrate beneath a portion of
tbe retinal detachment; and a neovascular process or
acute swelling of tbe RE1!: cells (figure TT.T2).JJ A pecu­
liar pseudopodal extension of the subretinal exudation
and subretinal hemorrhages were present in some cases
(I'igure 11 12A). Irregular staining of the subretinal thick­
ening angiographically simulated (hat occurring with
subretinal neovascularization [Figure 11.1.ZC). Complete
staining occurred in late pictures. En spile of the appear­
ance, lhe subretinal exudate disappeared and visual acuity
returned lo nearly normal. A characteristic "bull's-eye11pat­
tern of pigment epithelial atrophy in the macula persisted
(E'igure 3!.!2I.]. No patient had a recurrence. One palienl
had late development of subretinal neovascularization.
Fish and coworkers presented a similar case that in addi­
tion showed evidence of a pseudohypopyon in the macula
during the acute phase of the disease.1"1 ' Yaniiu/Jii's group
broadened the spectrum of this disorder lo include eccen­
tric macular lesions, subretinal exudate, fellow eye involve­
ment, papillilis, and an association of the disorder with
pregnancy and acquired immunodeficiency syndrome
(A ID S].1-*
In 2004, IJeck et al. reported 2 patienls with acute idio­
pathic macuiopathy following hand, foot, and mouth
disease wilh the characteristic sore ihroat, fever, and ery­
thematosus papules on the palms of hands, caused by
Coxsackievirus.'ilt They demonstrated elevated acute and
convalescent A 16 and liters for the vims. Both patients'
children were also diagnosed with hand, foot, and mouth
disease. MulLifocal IR G shows transient outer relinal dys­
function that recovers over lim e.131 Other rare associations
have been a macular holer recurrence at the same site,
and transient electro-oculogram impairment,
may show involvement of the in [ter choroid, likely from
contiguous spread of pathology.1 Spectral domain OCE'
shows thickening of the EiE4: and photoreceptor layers in
Lhe acute phase (E'igure TIT 2D) and restoration of most
11-12 Acute idiopathic macuEopalhy.
Д - G : This 31-year-old wom an had a sudden painless decline
in Vision to 6/2.Gp ir tie* left eye. Vision in lhe riyht eye was
20/20. Hif^bL fundus was normal. A soJilary distinct flal yel­
low placoLd lesion was seen in lhe macula with a few flecks
of relinal hemorrhage (A . An^io^ram showed brilliant stain­
ing o f [he relinal piemen I epithelium (Б and Cl. O plical
Coherence1 tomography ( O f Ti r e v e le d Ihickeninj" and dis­
turbance in the pholorecepLor layer (D . Ky history she had
Jesions in her mouLh and her coxsackle Liters netLUned ele-
uaEed. Rapid plasma rea^Ln was negative. Her vision began
[о improve after Л weeks of onsul, Ihe O C T showed gradual
recovery of pholoreceplors at 5 and 9 weeks it and F :, and
final vision improved to 2tV25 hy EO weeks, Fain! pigmen­
tary changes remained in the m acula (G).
H —| : A 2 8 year o ld H is p a n ic m a fe h a d a n a c u te d ro p o f
V isio n in h i5 left e y e to 2Q/40CJ o v e r 5 d a y s . A s o lita ry ye Flo w
f^ray p la c o id lesion w i lh m in im a l o v e r ly in g subneLinal flu id
i l-E i IhaL stained IHie o n I h e anj$io£>ram w a s seen i] an-d j). H e
re c a lle d h a v in g a sore th ro at 1 w e e k p rio r a n d w a s told by
his E’ Ch3 Lhal h e h a d c o n tra c te d h a n d , fo o t a n d m o u th J d is ­
ease fro m his c h ild re n . A w e e k later his vis io n had im p ro v e d
s p o n ta n e o u s ly lo 2 0 / 4 0 a n d hy .1 w e e k s to 2 t Y 2 Q w ilh m in i­
m a l p ie m e n La Iio n .
К and Lr This 21-vear-old woman complained of acutu loss
of vision in lhe ri^hr eve upon awakening. She noli Let! an
initfal bri^liL Siyhc in Lhe cenler ot her vision LhaL progressed
to a black central scotoma over Ilie next few days. This was
preceded 1зу a upper lespiialory infoci ion, hi^h fever, and
headache 1 week prior. Past medical history was unremark­
able. iiho was a smoker. Visual acuiLy was 2П/150 in Lhe ri^hl
eye and 20/20 in Ihe iel't eye. Color vision was 5 oul of 14
on the right and 14 out of 14 on the left. AmsEer grid showed
a lar^e central scoloma. A rin^-shaped yellow-while lesion
was present in the fovea. Fluorescein anyio^ram sEtowed a
window defecl cOtrespondjjftg to Lhe.1lesion чэш! late stalfiing.
Visual acuily aI .J weeks remained aL 2tVl 50. Al I T weeks.
I.in.1vision had improved sponLaneouslv to 2ti/3Qi
ГА- U . E d L rio y ill LJr. ЕСДШЫк H a JjflW flir: И И p. u iU rta v al I Jr. M.irk
LJiiily; К 1, LHjUrtciy 1'I L)r. L.ilvin Mein...'
o f Lhe photoreceptors late [Jigure T1.12E'). The central part
of die lesion is hyperaulofluorescent and the outer ring
hypoaulofluorescent, corresponding to the bull's-eye pat­
tern. No specific treatment has been attempted as most
cases have shown improvement En vision, including the
eye wilh two recurrences.1
U N I F O C A L H E L IO ID C H O R O ID JT 1 S
This condition is characterized by a solitary, elevated, yel­
low-white active focus of choroiditis xvilh overlying sub-
retinal Hu id, and in some cases sub retinal hemorrhage,
lhe lesion is approximately une disc dtaint;ter in size With
a halo around it, giving the name "fielioid'1 or sun like
(Figure 11ЛЗА and H ). On follow-up, the lesion shows
minimal growth and the sub retinal fluid resorbs gradually.
No other signs of ocular inflammation are usually pres­
ent, though a few anterior-chamber or vitreous cells have
been noted occasionally. On follow-up, the elevation per­
sists, even though the lesion turns more while and fibrotic
(E:igure 1 1 . 1 ЗА); a few show recurrences with reaccumula-
Lion of subretina] fluid [SR}:) and some d e v e l o p a CNVM.
Jhe active lesions are hypofluorescent early in the angio­
gram and stain late. rl"he inactive lesions show staining
(figure 11.L3B and C). The elevated lesion is hypoaulo-
fluorescent with a rim of increased auto fluorescence out­
side its edge [figure ]] ]3D). Visual loss is related to the
Location of the lesion and SJ?Б in the vicinity of the fovea.
Since the original description of 6 eases by I long et aLrJit
Shields et al. reviewed 60 cases that resemble this condi­
tion that they termed "solitary idiopathic choroiditis/'1'
11,13 Unifocal helioid choroiditis.
A —G : Th is 1 9 -y e a r -o ld w o m a n c o m p la in e d o f a s h a d o w
o v e r h e r v is io n in the left e y e for a y e a r o r Eonger. V isu a l
n t u ily w e b 2(1Л 5. o n 1 Ь е ? т a n d 20/215— o n Lhe reft. A s o li­
tary raised y e llo w w h ile lesion [hat app ears to b e o ld w it h
cle a rc u l m a rg in s , in c re a se d v a s c u la rity ir ils s u b s ta n c e b d m :
m u n ic a lH Jy w iLh the fjv e d y in g re tin al L'essuJs, is seen supeiro-
Ьегпрйга! Lo the fo v K L ( A . L t t e flu O re S c e i^ ani’ ioj’jarri shim 's
m ild sLain-ing o f lh e lesion ■'If a n d С ) I ha I d o e s noL fill w i !h
in d o c y a n in e gTeen (D): U lira s o u n d В scan a n d o p tic a l c o h e r­
en ce to m o g ra p h y s h o w [h t1 lesion lo h e raised i t nind hi. Th e
Eesion is h y p o a u C o fIu or-e scert, lik e ly d u e Co th in n in g o f Lhe
o v e rly in g retinal p ig n xfn L e p ith e liu m ( C ^
H : A m o r e a c u te le s io n in a n o th e r p a lie n L w ith Lhe ty p ic a l
'h e lio id ' or s u n iik e i^p pearam je a I Lhe e d g e .
ifjGUhfr^y оГ Ur. Lt;e I.: 11:>:-ijI. ■
Systemic in\restigations and corollary *)CLilar or systemic
features for infectious etiology such as histoplasmosis
and various fungi, tuberculosis, toxoplasmosis, or non­
in feetious etiology such as sarcoid or other granuloma­
tous disease, are negative. No treatmenl is necessary’;
systemic steroids have been used for those lesions that
xvere vision-threatening.
A C U T E R ET IN A L P IG M E N T
E P IT H E L IIT IS
Krill and Deulman141 described the syndrome of acute
retinal pigment epitheliltis, which is characterized by lhe
rapid onset of visual disturbances in one or both eyes
of young adults followed by gradual and almost com­
plete recovery in 7-10 weeks. 142 One Lo 2 weeks afler
the onset of symptoms, these patients had multiple clus­
ters of discrete, round, dark spots surrounded by depla­
mented halo!ike zones present at the level of the Kl’b in
the macula and paramacular area (Figure 11.14 L| These
were usually one-fourth disc diameleF Ln size, 'ihe fundus
findings during the first week after the onset of symptoms
were not described. Fluorescein angiography demonstrates
a halo of hyperfluorescence surroutiding Lhe dark spot
seen ophthahnoscoplcally {Figure ]J.]4 b , C, and 1.). In
some cases, angiography may be essentially normal. Ihe
Loss of visual function is out of proportion Lo the changes
seen in the macula. After recovery of central vision the
RPh changes may be barely visible. Ihe cause of this self-
Eimlted disorder Is unknown.
Since the original description by Deutman and col­
leagues, few reports of this condition surfaced till
2007.“ 1141 Chlttum and Kalina reported S patients with
acute retinal pigment epithe!Litis associated with a fine
pattern of pigment stippling confined largely to the foveo-
Ear area.1' 1Et was mostly twlleved lo he a nonspecific find­
ing secondary lo a Variety of circumstances, including
idiopathic central serous chorioretinopathy, drusen, adult-
on set vitelliform foveomacular (pattern) dystrophy, and
occull choroidal neovascularization, and in asymptomatic
patients.
Since the availability of OCT, case reports of acute reti­
nal pigment eplthellitis have re-emerged.1’ ' 1” ОС!'
shows iiyperreflecLivity at the level of the outer nuclear
Layer, photoreceptors, and ftPE (Figure LL.L-lll>and G ).The
disease is self-limited with near-complete visual recovery
in Ю-12 weeks (Figure ]].]4 ]J.
И . I 4 Acute retinal pigment, epithelium
Л —I : 1 h iн it a 2 G -y e a r-a |d л ч ш п п w ith a paracenlral "ц га у
н р о Г in her righ: e y e w ilh o u l a ts o c ia ln d p a in . redness, or
phtrfopsiti. iihe b a d had a d ia rrh eal illness Eird fFu Э w e e k s
p re v io u s fy Lind h a d re lu m e d fro m S o u lh A m e r ic a a n d Pt*TLi 6
г u i:i ih\ i:-i.: i V lie - v i-.i-: jn \ . i-. j : ■j 1 o n the r ;j,I ■i ,‘ : к I 1 \ i j ' : 1
on [h e le ft lYiere was a 5 0 0 -. m -s ize v e llo w Jesion su p e rio r
Lo fixa tio n W ith iiid is Jin O m argins LA I [hah w a s 1;уреп|1иогек-
cen( e a d y a n d lhe iSUr-raunding retina sla ined late (B a n d C ).
O p 1 ic .il c o h e re n c e Lomo£$raphy re ve a le d m ild ch a n g e s in the
p h o to re c e p to r layer (D>. A w e e k Jater h e r vis io n d ro p p e d lo
2 0 / 7 0 a n d Ihe lesion b e c a m e m o re d istin ct (E). A n g io g r a m
s h o w e d il w a s m a d e u p ol several snta]] d o [s , w ith disTuplion
,™ d po ssib le in fla m m a tio n in lh e p h o to re c e p to r a n d relinal
p ig m e n t ep ith e lia l layers (F a n d C ) . V ira l tilers fo r c o xs a ckie A
aл d b, hepatiLiH, d e n g u e , a n d rapid p ris m a reagin wore1 л ец а-
rive. A d ia gno sis o f a c u le relinaJ p ig m e n t e p ilh e liilis w as m a d e
ллd sh e e le c te d [o b e U e a te d w ilh oral отеЭотй ГОй G O mg/
day, Lapered o v e r 2 . 5 W eeks. H e r v is io n im p ro v e d to 20/25
2 w e e k s post p re d n is o n e th e ra p y ; the lesion Jsec-ame sm alle r
a n d iлас live ( H w i[h re s lu ja lio n o f m u tl o f ihtt p h o K ire c e p Lo r
layer l>.
I a n d K : This 2 5 -y e a f-o ld w u m a n n o le d p h oLop sia, b lu rre d
v is io n , a n d m u llip le ратасел1га1 s t o t o m a b in [h e righ I e ye
1 2 days b e fo re her e x a m in a tio n a[ the Ba$corn Fu lm e r Eye
[n slilu le . W h e n e x a m in e d by h e r local p h ysician several
days nfler lh e onsel her acuiLy w a s 2 U /2 0 a n d lh e fu n d u s w a s
d escribed as n o rm a l. O n e w e e k laler her a cuiLy w as 2 0 -3 0 a n d
som e " y e llo w m aterial w a s noted m lh e ri^ht m a t-u la.'' A t the
K a s c o m Ftilm e t Ly e Ins1itu1e h e r a c u ily w as 2 0 ^ 2 5 . (ytub iplo
paracentral scotom a La w e re denvnnstrable o n th e A m s Je r ^ rid
in Lhe right e y e . T h e re w e re n o v itre o u s cells. T h e re w e re m u l­
tip le, sm all p i^ m e n le d iesions s u rro u n d e d bv d o p ijjm e n tp d
halos at the level o J th e R F E (arruw^ j). T h e lefC fu n d u s w a s nor­
m a l. A n g io g ra p h y repealed sm all h a lo s o f h ^ p e rfiu n re s c e n te
c o rre s p o n d in g w ilh Lhe lesiun-s (a rro w s, K.l. ^ h e w as last seen
b y h e r local p h ysician Б m o n th s al"[er [h e o n se t o f s ym p to m s .
Visua l acuiLv w as 2 0 '2 0 , and Iht! fLindus w as n o rm a l.
l A - l , ( .U lL ir iL ^ y u f U r . M . h r k i D f t l l S D n . )
MULTI P it EVANESCENT WHITE-
DOT SYNDROME
lhe following features characterize MKWDSr which typi­
cally affects one eye of young females: (1] blurred vision.,
multiple paracentral scotomata, usually including a tem­
poral scotoma, and photopsia occurring in approximately
one-half of patients soon after a fiulike illness; (2} vitreous
cells; [3J multiple small, often poorly defined, gray-while
patches at the level of the К H i and outer rclin.t [Figures
11.15 and 11.16); [4) a cluster of ti ny wh ite or Eight-orange
dots in the foveola (I'igure M .I5A); (5) early punctate
hyperfluorescence of the gray-white patches, which often
show a cluster or xvreath-shaped pattern {I'igure 31.15С
and II); [6] late fluorescein staining of these lesions, and
in some cases staining of (he optic nerve head; [7) blind-
spot enlargement; (8) decrease in the 1LRC. a-wave and
early receptor potential amplitudes; and (9 ) spontane­
ous recover}' of visual function, normalization of the
electroretinograpbic findings, and return of the ophthal­
moscopic and angiographic findings toward normal in
7-10 weeks (figure 11.16(5-1).1 The white spots in
MKWDSr which are often smallr ill defined, and located
in the extramacular area, are easily overlooked. It is prob­
able that most patients reported as having Lhe acute idio­
pathic blind-spot enlargement syndrome166 probably had
M E i W D S , and that the white lesions were either overlooked
or had faded at the time of their etam inalion.11" ' ' ' л
M . E5 Multiple eva nesce nI wh iLe -do t !>vndrome
(MEWDSK
A .l^-year-ri’d moderately m yopic Worrvin noled several
siniill I>!in-cJ spots in her ri^hl ccnlral field associated w ilh
photopsias of 5 days’ dura!ion. H e r vision was 20/40 on the?
riц.Ъt and 20/20 olii lint! left. Several i^ray яр(Ин went? seen scat­
tered in lbe rijjhc t-un-clLis :A—L.T: a n d orangp dots in- lhe fovea
iA . Ajlofttfbrescence ima^in^ showed hy$^L(toflUDre5&fcrce
corresponding to lhe lesions (Ё), opli-cal cuhe№nq^ tomogra­
phy showed loss of photoreceptors in the affected эдгау spols
if!'. An enlarged blind spol was found on Hum phrey field
testing. l-luoruscern angiography showed rin^ of hvperflui.)-
rescent dofa consisluni w ilh "w realhiifie" spots. A diagnosis
Of M L W H S w n i made and she W as kepi undfef observation.
К у I weeks- her vision had improved lo 20/20, die pho-
topsias h a d re s o lv e d and m o s t Ы the g ra y spots had disap­
peared, orahge dais were still present. The iosion inferior
L(] fovea appeared I о he whiter and i пас live, ih e moved 1o
SeattSp nn-d ta iled 1 years hi lei com plaining a t new m e la -
fn p m g r a ftia superior Co fix a! io n . ih e had developed a c h o ­
roidal neovascular membrane at (he site o f J be persistent scar
(a rro w A.I and received inlravitreaE antivascular endothelial
unowth factor injections.
 ICG aLigtography detnonstrates patchy hyperfluores­
cence At lhe level of the JtETE-' as welE as multiple, small,
round, hypoflu orescent. lesions, some of which occur In
tbe absence of fundus changes.' ' ' Although fluorescein
angiography oflen shows some staining of the optic disc
during lhe acule phases of the disease, there is minimal
evidence (hat damage to (he retinal ganglion cells and
optic nerve is responsible for visual lots. Il“' L.ater in the
course of the disease a zone of Eil'H depigmentation and
hyperlluorescence corresponding with their en larked blind
spot or other field defect may develop.1 ' -'■ ' Subretinal
neovascularization may occasional I!y occur.17' " ' Scanning
laser densitometry demonstrates evidence of j focal defect
in the visual pigment kinetics of lhe receptor cells in lhe
macular area.1 7 liq u a tio n for evidence of systemic
disease is usually negative. Some visual field loss and color
vision defect may persist.1'^ ihe cause o f the disease is
unknown. Males may be affected, the disorder may occa­
sionally atfecl both eyesr and late recurrences may occa­
sionally [n &оше сдье5 vlsu^
field defects do not resolve.111
fie fore or fallowing .V1HWD5 some palients develop evi­
dence of pseudo-POI-]S.- acute macular neurorctinopathy,
and acute onsel of Eaige visual field defects unassociated
I 1. E Multiple evanescent while-dot syndrome,
1 hfs I-t-ye -a r-o id W O tn a n c o m p la -in c d a f [огпрогаЗ floaters
л» d ibcCasibfiaJ flashes; o f 3 in bet ri^hl e y e D l 5 d av^'
d u ra tio n . She h a d h is-Lcjry o f m i^ r.im tj. H e r v is io n w a s 2E1/20
in e a c h e ve ; n o vis u a l ■it’ Td d e fe c t c o u ld Eje Bfem orfatrated
on Ib fm a l LesLin^. A fe w w h ite ыроЕы in Lhe m a c u la , o ra n g e
dcris in lh e fo v e a I cenier, a n d several sp ols in lh e m id p e r ip h -
e rv w e re seen ( A , B , a n d C.ji. A n ^ io ^ r n m s h o w e d w re n I hi i ко
h y p e r flu o w ^ te h c e a f ih u m a c u la r lesions <tnd h y p o rfEu o ie s -
c c n c e o f Ihe [гкГга тщ л М а г Seniona I L a n d D ) . O n a u C o flu o fe s -
c r n c e im a ^ in jj lh e lesions w e re h y p o a u lo fiu o re s c e n L . ь a n d
F-:. A w e e k later s o m e o f Lhe w h ite le sion s had d is a p p e a re d
( H ) a n d b y i m o n th s Ihe fu n d u s w a s b a c k Lo n o rm a ! w iLh o u l
e v id e n c e erf д п у lesion lli.
with visible changes in Lhe fundi.1 1 [here is
evidence that \lliW D5 may be pari of a specimm of one
disease or cEoseEv related diseases that include acute idio-
palhic blind-spot ^ j a i g e A Z G O R
(see discussion to follow), p s e u d ^ P O H S ,^ 175-1*1'1* 5-1^
and acute macutar neuroretinopalhy.|:'! 170,161 AlS of the
disorders affect predominantly young women and all
may present with photopsia and zones of visual field loss
caused by retinal receplor damage unexplained by biomi-
croscopic changes in Lhe ocular fundi. ■:'1
ACUTE ZONAL OCCULT OUTER
RETINOPATHY
1q 19У4 Gass reported 13 patients, predominantly young
W D # D r with a syndrome characterized by rapid loss of
one or more large zones of outer retina! function, photo p-
sLa, minimal, fundoscopic changes, usually mild viiritis,
and electrorelinographic abnormalities affecting one or
both eyes [E'igure I1.17J.'::J Progression of visual field loss
occurred over a period of several weeks or months before
either improving or stabilizing. Involvement of the second
eye may be delayed for nit least as Song as 2 years [figure
11. i 7A—[). All patients on follow-up ем mi nation had per­
sistent visual field defects, and most had chronic photop­
sia and zones of pigment epithelial atrophy and retinal
vascular narrowing, which in some cases mimicked that
seen in retinitis pigmentosa and cancer-associated retino­
pathy (figure i l -17I-L) in some patients large, perma­
nent, visual field defects were unassocialed with any
visible changes in either the fundus or in fluorescein
angiograms.
Most patients wilh AZOOR are у along or middle-aged
adults wilh the predominance of women, who present
wilh an acule onset of visual field loss in one or both eyes,
lh e fundus exam illation reveals no abnormalities al onset.
More than 50^-ii of palients have antecedent or associated
pholopsias, which are projected to the zone of visual defi­
cit. lhe pholopsias have been described variously as "fire­
works, blinking lights, movement of microbes under a
microscope, the IV screen being off signal, Hashes of light,
heal waves coming off lhe road, and other visual phenom­
ena/ A characteristic finding is the description of ”move­
ments" associated with these photopsias. Salients oflen
move their fingers or hands while describing the symp­
tom. Unlike in posterior vitreous separation, the pholop­
sias are more noticeable in bright light and patients have
been known to come into the doctor's office wearing sun­
glasses lhe photopsias can predate, appear simultaneous,
or antedate the field loss. Some patients may have had an
antecedent viral illness. I hose eyes ivi.r_h large areas of field
loss, signifying involvement of a large zone of photorecep-
torsr may have vitreous cells. However, vitreous cells may
be a later phenomenon, seen when photoreceptors die.
The visual field defect is variable; it can be small or taige,
and often is connected lo the blind spol. Sometimes the
field loss is in the periphery.
The subtle nature of this presumed inflammatory dis­
order, which causes acule damage to broad zones of the
outer retina without producing noticeable ophthalmo­
scopic changes, is responsible for the diagnostic confu­
sion that usually results in extensive fruitless neurologic
medical, and ophthalmologic consultations and labora­
tory investigations. Demonstration of eleclrorelinographic
abnormalities during the early course of lhe disease is
helpful in this regard. I"he EfJGs in these patients show
a paltern of visual dysfunction lhat is photoreceptor in
I 1. 17 Acute zonal outer retinopathy, occult lype.
A-С: Th is ? 4 -y e S r-tild w o m a n , w h ile: re c o ve rin g fro m an
u p p e r respiratory in le c lio n , e w e ftfitfid B d rap id severe loss o f
vis io n n ve rn ig h l in b o th eyes. Visual a c u ity in [h e right e ye
was 2 LV 2 0 0 . Гe -11 e y e 2(1/20. У Ид bad severe p d h s b id ^ iff o f Lhe
v is-LFiiI field Ш1а1нга1 ly. Etdtn fund i Lind а ngiugram s. a p p e a re d
n o rm a l IA a n d E 3 S e v e n m o n th s Iinter sh e h a d bilateral p h o -
Lopsia; persislenl, severe visual field d efects; n a rro w in g o f the
retinal vessels; a n d w id e s p re a d h y p o p rg m a n la Lio n o f Lhe reti­
nal p ig m e n l e p ith e liu m fR I’ ti.i m e re p r o n o u n c e d a n te rio r Lo
Lhe arcades (C T T h e v is u a l field loss re m a in e d slable b u t she
d e v e lo p e d m ig ra tio n o f p if^ n e n l into Lhe re tin a in a h o n e co r­
p u scle pnttern p e rip h e ra lly fiver ib e n e x l ye a r.
C L - li O v e r a p e rio d o f -several m e n lbs Lhis 3 b -y e a r -o ld
w o m a n d e v e lo p e d p ro g re s s ive fuss o f p e rip h e ra l v is io n , p h o -
Lop sia, v ilre o u s c e lls , n a r r o w in g d J lh e relina l vessels, n o n ­
slain in ^ ty s lo id m a c u la r e d e m a (a rro w , L?j, d e p ig m e n la tio n
□I Lhe K F’ b in Lhe ju x ta p a p illa ry a re a , a n d eloclrureLi n o g ra m
cha ng es in Ihe right e y e ( □ a n d EJ. V is u a l field Lass s ta b ilize d
w iLh in £ m o n th s , l'w e n ly -s is m o n th s after lh e o n se t o f s y m p ­
tom s in lh e rig h t e y e she d e v e lo fH id the s a m e s y m p to m ^ a n ti
signs in the left e y e lhal p re v io u s ly w as n o rm a l e x c e p I for
o n e ftxjal scar I arrow ,. F >. C o m p a r e F a n d Ci aL Lhe lim e o f
onsel o f s y m p L o m t in Lhe lefl e y e w ith H a n d Г 1 y e a r later,
a n d n o te d e v e |o p m e n L o f retinal vessel n a r m w iiM a n d d e p ig -
m e n ta Lio n o f th e ju K ta p a p illa ry F\h'E (a rro w h e a d s , If. T h e
visual field s ta b ilize d iri :iie lefl c y i1 w ilh in 6 m o n Lh s . H o lh
eyes have b e e n u n c h a n g e d for Lhe pasl 3 y e a rs . H e r vis u a l
acuiLy is 2 0 '2 a ri^ b t e y e a n d 20/2-0 3eft e y e . i h e has m ild
m p c u ta r e d e m a Ej i I literal Iv-
|—L : T h is 2*J-year-old wom an n o Le d lhe F ic u le o n s e t of pho-
Lopsia and '"shimmering heaTwave" involving Lhe supero-
nasal liefd of Lhe rrghL eye. T h e fundi were normal. M edical
anti neurologic examinations w ere unremarkable. H e r
visual acuily was 2 0 '2 0 in iio Lh eyes. W ith in 1 month she
develofied a EUtie erf depjgmentation and several locL o f
perivenous shea I King a n d slain inf; Narrows, I and Kj infero-
ii.-ii-|if i-1!!v in ii-1■:■ rib'll o .t. An d t’cLroreliiio^ram showm
subnoTmal rod a n d cone ampliludes in lbe ri^hL e y e . Th e
fundi and visual fields remained unchanged over the subse-
[]Lien1 (> years except for migration of pigmenl ini о lhe relina
(L) En the righL eye and the development o f several foci o f
perivascular shealhing in the left eye nasally, ih e is still Irou-
bled iiy the photopsia.
IA - L f r u a n C J ^ b i ,,! ''
origin, palchv in dislribution, and asymmetric in lhe two
eyes I f (he field loss is small and unilateral, Lhe ERG in
the affected eye may be reduced compared to the fellow
normal eye. If lhe field loss is extensive the EftG is below
normal in the affected eye[s}. Either the rod or the cone
function, or bolh, may be affected based on lhe location
of lhe visual dysfunction. Hi lateral involvement causes
ERG depression in both eyes. Interocular asymmetry was
a prominent feature in Lhe 24 palienls studied by Jacobsoci
et al.1 Mu III focal LEiG if available is useful in document­
ing the Extent and location of the field loss and is diag­
nostic of the condition when associated with a normal
fundus. J Eowever, since multifocal Е-ЖЗ tests cone futiclion
OLtly, iL will not be able lo pick up subtle rod defects.
 lhe field loss does not conform Lo the loss seen with
glaucoma or <i vascular defect. [JoEdmann visual field
mapping is important in demonsLraLtng lhe complete
field deficit, often associated wltfi an entailed blind spot.
Visual field defects stabilize within 6 months. Л small
percentage of patients show improvemenL in field defect
tf treated early with antiviral s and systemic corticoste­
roids. Fluorescein angiography when tbe fundus shows no
changes is norma] [I'igure U.17Aand ti) and shows trans­
mission hyperfluorescence in those areas of Rl3L change
(figure I l . l7 t r 1, and K). Aulo fluorescence imaging of
tbe normal fundus shows no ah normality г however, once
fiPE atrophy is seen, the areas appear hypoautofluorescenl
(I'igure 11.IS C }, and occasionally show a rim of increased
aulofluorescence.191
The cause of the acute damage to sharply defined zones
of the retinal receptor cells in the absence of visible fun­
dus changes in patients wilh A/OQR is unknown. 'E'here
is patchy evidence Lo date for autoantibodies to any reti­
naE cell type in palients with A /O O R.1"1' 1|J Gass postu­
lated the possibility of an inciting viraJ or other infectious
agent within the photoreceptors. He has hypothesized a
"silent pTechnical phase,11 where cell-to-cell spread of the
virus occurs, with retention of norma! photoreceptor func­
tion. tn lhe "acute symptomatic phase," tbe infected cell
dysfunction is triggered by the host immune response,
bllher a change in the antigeniciLy of the infective agenl or
a local auto-immune react ion to lhe receptors laden with
this infective agent may cause loss of photoreceptor func­
tion." 'Ihe finding that over 9СЯ4 of eyes with AZOOR have
visual held defects that include one or bolh blind spott-
and/ог the peripheral isopters, suggests lhal the ora ser-
rata and optic disc margin are possible sites for invasion
of a virus inlo the receptor cells. I'hese are two sites where
the retinal receptors anatomically are not isolated from the
systemic circulation by surrounding neuroepilheliutn. In
approximately half the patients with А/ЛХЖ, the immune
response to lhe intracellular virus results in inactivation of
function but preservation of the receptor cell. No bio mi­
croscopic or ophthalmoscopic evidence of inflammation
of acute or long-term retinal cell damage is evident, [n
most cases the retinal cel! dysfunction appears to be per­
manent. Although most instances of recovery occur dur­
ing the firsl 6 months after onset of symptoms, at least 2
patients demonstrated improvement in the visuaE field
after several years. Likewise, while stabilization of visual
field loss typically occurs within 6 months of the onset
of field loss, a few patienls, particularly those who show
evidence of some recovery early may develop a gradual
increase in visuaE field loss many months or years later.
Ihis delayed Eoss may occur as a resuEt of reselling of the
cells' apoploLlc clock during the initial acute phase of
AZOOR.
In lhe other half of palients with AZOOR. the iinmune
response results in early receptor cell death, development
M . 13 A c u te zo n a l occuEt o u te r re tin o p a th y .
A-£l Thiы -fO-ye n r-tj Id wonun prc^enled with a history of
rapidly prDj'i'tissive visual loss in h e r ri^hl eye over 1 - 2 years
лfjfjrcjjtiт л Lt1ly 10 years prior, and a recent lumpnral blind
spoL associated wilh ph ut(jpsia s ir her IcM eye. H e r s y m p ­
tom s began with photopsias and rapid progressive loss of
visual fiE^ld in h e r fi^ht eye. When I first examined her, the
vision in her righl eye was hand motions Lo counl lingers.
The left e y e was 2№20 wilh a lar^e temporal blind spol.
Tbe fundus in lhe righl eye showed widespread piemen I
alteration witb diffusely narrowed retinal Vessels, patchy
bone spicules (A ) , w h ile the lefl fundus was normal (B and
C j. O p tic a l coherence tomography Lh ro u g h the left macula
revealed loss o f p h o to re c e p to rs in lhe peripapillary area (□
a n d E arruwj in spite o f a n o rm a I-appearing retina. H e r e lo c -
tr o r d i n o ^ ra m n h o w e d n si^m ficrinl a s y m m e try w ith пImast
flat w a ve s on lhe ri^bt. Thu ledl eye continued Lo have fur­
ther field loss, th o u g h the fundus remained tidrm a® S h e w h s
Klarted on oral steroids anrl val a c y c lo v ir for 6 weeks and
this seemed to control fu rth e r progression. H o w e v e r on d is ­
continuation o f sler-uids she felt subjective w o rs e n in g o f h e r
fie ld , ihe was started o n melholrexate and mycophenolate
mofulil anrl is bein^ m o n ito re d .
F tn I: Late appearance of thu rijqhl and ledl fundus and aulo-
fkiorescence of a Ifi-yuar-nid woman wilh extensive
bitemporal fiold defect lhal has remained smbleover the pasl
10 years. Note the asymmetry between the nasal and tempo­
ral retina.
of a variable degree of inflammation including vitreous
cells, perivascular exudation, and occasionally oplic disc
edema. 'I'hese inflammatory signs typically develop within
several weeks following ttie onset of A/.OOR. appear to be
proportional lo the size of the affected retinal zones, and
probably result from an inflammatory response Lo the
dead retinal receptor cells.1''1
Weeks or months later, narrowing of the relinal vessels.,
particularly the retinal arteries, perivascular sheathing, and
reactive changes in the ftPE occur [E'igure 11.1вА and K).
lhe loss of interaction of lhe microvilli of lhe jfilPE with
itie photoreceptors causes migration of the ЙРЁ into the
inner retina to line up along the blood vesseE Wall, giving
the typical bone spicule appear,nice.
Similar acute occull zones of visual field loss that are
accompanied by EiRt; changes may occur in palients with
ME\VDSr1Si-|Ю M CP and punctate inner choroiditis [PEC),
(pseudo-lJOJ-E5),l6-Ll|,U::-?-lli:'J-i,,J'1 and less oflen tn patienls
with, or who previously had, acule macular neuro-
retinopathy.'1111:1 'ihe authors have seen aE leasl 50 olher
patienls wilh evidence of overlap between iylEWDS,
pseudo-POl Ei, AZOOR, and acute idiopathic blind-spot
enlargement syndrome. Whereas occult visual field loss
resulting from receptor cell damage is a common link
among all ihese syndromes, we do not know tbe cause of
any of these disorders or. to whal degree ihey are relaled
patbogenelically and etiologically.
ACUTE ANNULAR OCCULT OUTER
RETINOPATHY
In the Lhird edition of this book lhe author presented
the findings in an otherwise healthy young adult patient
who presented with лапе loss of a large xone of visual
field associated with an unique fundoscopic picture con­
sist ing of a large-dia meter, ihin, gray-white ring occupy­
ing most of the superior temporal fundus of the left eye
(E'igure И Л ЗА -F).193 Except for slight narrowing of ihe
retinal arteries within this zone, the retina and pigment
epithelium had л normat ophthalmoscopic and fluo­
rescein angiographic appearance (]Igure 1,1,1 [here
were no vitreous cells. "Ihere was a left afferent pupillary
defect. For л period of approximately 3 weeks the ring
and absolute visual field defect enlarged before stabiliz­
ing {Figure ]1 ]9C-J:). The ring disappeared. 'Jhe visual
acuity was normal throughout the course. The absence of
angiographic changes suggested that the occult destructive
process ivas affecting primarily Lhe inner retina within the
area of the ring and the disorder was termed "acute pro­
gressive zonaE inner retinitis and degene rat ion." During
follow-up over the following months and years, however
the patient developed, within the zone of visual field loss.,
depigmentation and migration of pigmenL epithelium
into the overlying retina in a bone-corpuscular pattern.,
indicating that the original damage had in fact involved
primarily the outer reLinal receptors (Tigure П.1ЯН and
I).1 During the G years of follow-up his visual acuity has
remained 20/20 and the visual field loss is unchanged. O f
interest, he no longer has an afferent pupillary defect.
Luckie and соworkers reported a young xvoman with
the identical findings and early clinical course in one
eye."'''' She had serologic evidence of cytomegalovirus
infection and they attributed her stabilization of field loss
to treatment with acyclovir, ihe fact that their patient was
immunocompetent suggests that her retinitis and clini­
cal course may be unrelated to cytomegalovirus and her
therapy.
Ixcept for the presence of the gray ring and the absence
of a history of photopsia during the лете phase of the
disease, the findings aitd course of the disease in these 2
patients are the same as those with AZOOlfc1^ --500 The
cause of the zones of acute occult outer retinal dam­
age in both groups of patients is unknown. An attractive,
yet unsubstantiated, explanation for the fundus changes
es that of a latent viral infection of selective zones of the
outer retina that is somehow triggered into activity, caus­
ing acute inactivation of function and in some cases death
of the retinal receptors within those zones without afTecl­
ing retinal transparency [except for the ring) and withouL
afTecling either the outer or the inner blood-retinal barrier
M . EQ Acute го nal outer ret in opat hy, a nn ula r occ ult
type.
A —I: A h e a Eth y 2 3 -y e a r-o ld m a n n o li L e d [he ra p id o n s d o f
я lar^e in fe ro n a s a l s c o to m a in his left e y e . H is vis u a l a c u ­
ity w as 2 0 / 2 0 . W h e n seen Eiy h it local o p h th a .m o lo ^ in l, I he?
right WflS n o r m a l. T h e a n te rio r c h a m b e r a n d v ilie o u s
w e re d e a r . In th e left fu n d u s (h e re w a s a s h a rp ly d e fin e d ,
th in , ^rnv. c irc u la r rin ^ iarm m 's, A a n d K.i D t c u p v in q люк1 tif
the s u p e ro Ee m p o ra l q u a d ra n l. Ih e j^ray rin ^ b p p e a te d to b e
w iLh in the rm ina b u l w a s e x te rn a l to the retinal vessel h. Jl
e s te n d e d o u l Lo Ihe e q u a lo r bur d id not reach Ih e o ra ser-
rata. Ih e relina w ilE iin the rin ^ a p p e a re d A o n r id L V isu a l field
e x a m in a tio n ra re a le t) a d e n se ic a lo m a jcn rK ^ p c m d itta Lo the
г с п е w ilh in the r in g . O v e r ih e n e xt W n k lh e s c o to m a p ro ­
gressively e n la rg e d . W h e n e x a m in e d in M ia m i th e ддау rin ^
w a s b a re ly vis ib le fa rr o w s , C - E ) . T h e z o n e w ilh in the rin ^
h a d gblarjgpd (с о т pare a rr o w s , A a n d В , w ilh (" anci J.?i b u l
d id n o l re a c h lh e c e n te r a f the гп а С Ц Щ l h e d ia g ra m |F ] iil-us-
trales Lhe c h a r g e in s ize o f the r in ^ . T h e retinal vessels w ith in
this z o n e w e re h a r r o w e d , a n d d ie s u rfa c e reLrnat reflexes
w e re H lle n u a le d . l h e retinal p tfrn e rtt e p ith e liu m ( R f f J W as
u n a ffe c te d . Flu o re s c e in a n yio jjra p h iy i t m i firm e d Ihe a tte n u a ­
tio n o f the retinal vessels; a n d the n o rm a lity o f the Й Р Е : G : .
O v e t the s u b s e q u e n t several w e e k s th e s c q h im a ем la rk e d
slijihlly a n d iben s ta b ilis e d . W ith in severa l years h e d e v e l­
o p e d d e p i^ т е Ш н И io n o f the К.ГЬ a n d m ijjra lio n o f pi^^ntm L
in to lh e re tin a w ith in Lhe z o n e o f visuar field Ios? Ia rro w s , H
a n d Ij. H is visual a c u ity 6 .5 years EaLer w a s 20/20. T h e right
eye w a s fic r m a l.
lo fluorescein during lhe acule phase of the disease: The
evanescent ring of retinal opacity occurs at the interface
of the affected and unaffected outer retina and probably
aL the level of the outer plexiform layer and receptor cell
nuclear layer, where it causes no angiographic abnormal­
ity. '['he ring may be the result of loss of transparency of
the most recently affected retina, similar lo that whicti
may be seen in immune-suppressed patients with cetl-
lo-cell spread of cytomegalovirus retinopathy.-43- 'lhe ring
may also be caused by a mild immune reaction taking
place at the interface between the normal vascularized
inner retina and the Leading edge of the advancing infec­
tion in the outer avascularized retina, similar to that which
may be observed in the cornea {Wesley ring). Neither
explanation is completely satisfactory in view of the
absence of delectable abnormality in either the inner of
lhe outer blood-retinal barrier. Anliretinal antibodies lo
in tier nuclear layer; and ganglion cell layer, and in another
case to outer nuclear layer additionally, suggests auto­
immunity may play a role.-01 However, it is not known
whether the antibodies are primarily involved, or develop
as an epiphenomenon. The lesions appear nonfluorescenl
on ICG angiography once RPE changes have ensued.-0’
 Ngure 11.20 illustrates what may be a further vacant of
AZOOR (annular overt type) Ln which lhe affected zone Lb
associated with acute disruption of the ]U>h and variable
degree of whitening of the outer retina and JJE’Ei.
I 1.211 Acute zonal outer retinopathy, annular type.
A-E; lh ;s p Q -y ^ & r-u ld w o m a n w ilh c h ro n ic fa tig u e s y n d ro m e
n o te d Lhe s u d d e n onsel erf a la r^ e nasal s c o Lo m a in lh e telt
e y e . V is u a l a c u ity w a s 2G J2 0 r righL e y e a n d 2 Q / 4 0 0 r left e ye .
S h e h a d a d en se s c o to m a c o rre s p o n d in g w ith a large s u p e ro -
Lem p oral z o n e o f retinal p ig m e n l e p ith e liu m (K P E ) d e p ig -
m e n ta Lio n s u rro u n d e d b y я b o rd e r o f o u te r ToLi пл1 w h ile n in g
i A a n d lb. This w a s assoc inled w ith 2 - v ilr ilit. A n g io g r a p h y
re ve a le d e a rly n o n flu o re s c e n c e o l Lhe rim o f the lesion a n d
h y p e rflu o re s c e n c e c o rre s p o n d in g to im cenLer (C ), a n d laLe
i :u o re s c e n c e o f th e e n tire le s io n . M e d ic a l e vH ^u a tio n , i n d lad­
in g lilers for s y p h ilis a n d h erpes viru s e s , w a s n e g a tiv e e x c e p l
fur m ild Ih ro m b o c y to s is a n d g ra n u lo c y to s is . She w as h o s p i­
ta lize d a n d re c e iv e d o ra l p re d n is o n e , a c y c lo v ir, a n d d o x y c y -
t lin e . V isu a l a c u ily im p ro v e d lo 2 0 .-70 w ith in 1 w e e k , O v e r
Lhe lo llo w in g 5 w e e k s it d e c re a se d Lo 2 0 / 4 0 0 a n d lh e z o n e
ot K F’ lb d e s tru c tio n (.o n lin u e d In e n la rg e in a nasal d ire c -
Lion ( D j . F iv e m o n th s afLer the onsel o f s y m p to m s a lm o s t
the e n tire fu n d u s w a s a ffe c te d i t . , b u L v is u a l a c u ily h a d
im p ro v e d Lo 2 0 / 2 0 0 a n d c o n tin u e d to im p ro v e o v e r lh e n e xl
y e a r to 2 0 У 3 0 . F o u r years tater her c o n d itio n w a s u n c h a n g e d .
The righl e v e w a s n o r m a l.
Acute zonal outer retinopathy, overt type.
F - L : S oorl after d e v e lo p in g a ?ore th ro a t Lhis o th e rw is e
p e a Jth y q O -y e a r-d fp m a n c o m p la in e d o f progressive 3<?ss o f
i; il - U 'm p o u l i c d " l vis io n in ihr ler: j.'y-L1 as^ot i.iM-d i: I■
" s h im m e rin g lig h ^ o f 2 w e e k s ' d u r a tio n . N i n e m o n th s p re ­
v io u s ly h e n o le d a sim ilar huL m o re p e rip h e ra l te m p o ra l
s c o to m a in Lhe right e y e a sso ciate d w iL h " s h im m e r in g .'' T h e
s y m p lo m s in lh e right e y e re s o lve d s p o n lan e o-u sJy afler s e v ­
eral m o n th s . H is visual a c u ity w as 20^20 b ila te ra lly . There
w a s a 3 +- affere nt p u p illa r y d e le c L in the left e y e . V isu a l
field e jta m in a tio n re v e a le d a d ense s c o to m a in v o lv in g m osL
ot lb e p e rip h e ra l a n d a lm o s t al o f lh e Le m p o ra j vis u a l field
o f th e left e y e r a n d a n e n la rg e d b lin d spot in ih e righl e y e . In
the righL e y e (h e re w e re 2 + v itre o u s cells a n d a la rg e w e ll-
d e m a rc a te d z o n e o f R3J b a tToph y in v o lv in g lh e ju x ta p a p -
b la ry a n d in fe rio r a n d nasal areas o u l as far as lh e e q u a to r
(Fh_ Tini5 area w a s far la rg e r th a n the z o n e o f visuaE fie ld loss.
T h e o p lic disc a n d retinaJ vessels w e re n o rm a l bi la Lera 11 y.
F u n d o s c o p ic e x a m in a tio n o f lh e let"! e ye re v e a le d 3 - viLne-
ous cells a n d a s h a rp ly d e fin e d г о п е o f d is ru p tio n ot Lhe K iJt
in v o lv in g m ost o f lh e fu n d u s b ul sp a rin g m u c h o f Lhe m a c ­
u la r a re a lG ) . There w as n o g r a y -w h ite d e m a rc a tio n iine aL
lh e b o rd e r o f Lhe K K t c h a n g e . Te m p o ra l to Lne m a c u la , h o w ­
ever, ih e re w e re several ill-d e fin e d areas o f g ra y -w h iLe aL Ihe
le ve l o f the K .K E ( H I . In the lefl e y e flu o re s c e in a n g io g ra p h y
s h o w e d e v id e n c e o f a c u le Rl-1!-. d a m a g e b ul n o e v id e n c e ol
in v o k e m e n l o f the th o r io c a p il laris (J a n d K ). In Lhe righl e ye
Lhere w a s m oLLJed h y p e rf lu o re sce n ce c o rre s p o n d in g I о lh e
large a re a o f o ld K P t d a m a g e ill. H e re c e ive d p re d n is o n e ,
00 m g , a n d a c y c lo v ir, 4 g , dail'- h y m o u lb . There w a s s o m e
prog ression ol" Ihe vis u a l less a n d biF’ t ( iianges in lh e left e v e
for several w e e k s b e fo re s ta b iliza tio n ot c u n e d 'l .l as seen o n
Lhis fu n d u s p h o to g ra p h .
DISORDERS SIMULATING
THE PRESUMED OCULAR
HISTOPLASMOSIS SYNDROME
(PSEUDO-POHS)
Jhe clinical features of [1O tIS are described in Chapter 3.
In recent years LL has become apparent that there are other
disorder, unrelated to infection with НйЯорйыВД that
during Lheir inactive stages may саше a pattern of chorio­
retinal scarring similar to POH5. Collectively referred Lo
as psetido+РОНЯ there are at least two groups of patients
that may simulate P OH ы ад T h ^ may or
may not be palhogenetjcally related and are termed mul­
tifocal choroiditis with pan uveitis (M CP) and punctate
Ш ner choro id i tiб ( PI С ) .
MULTIFOCAL CHOROIDITIS AND
PANUVEITIS_______________________
Nozik and l>>r&chjl)!i and Liter EJreyer and G as!^ ' and
'lessler and Deutsch'IJ described a syndrome of MCP that
simulates POEIb with the following exceptions: ( I ) vitre­
ous inflammation is present in one or both eyes; (2) ante­
rior uveitis occurs in 5G^i of cases; (3 j yellow and gray
active choroidal Eesions that angiogjaphically may be
nonfluorescent early and slain later are often observed or
may develop during follow-up (figure 11.21A-C); (4) the
inactive lesions are in general smaller than those in the
FOHS (Rgures 11.2IA-C and 11.22Jr (5) most patients
come from areas nonendemic for histoplasmosis and
have a negative histoplasmin skin test; (6) approximately
one-half of eyes demonstrate subnormal electroretino­
graphic f]tidings (figures 11.21 L>—]J and 11.22); (7} some
patients develop acutely large visual field defects that are
not explained on the basis of fundus findings and subse­
quently may develop large areas of Rl’ti depigmentalion..
which may he associated with retinal vessel narrowing
and migration of pigment epithelium into the retina:
(a ) patients with monocular involvement [25 % ) may
develop severe involvement of the second eye months or
wars later (I'igure 11.2.2); (9) there is a female sex predi­
lection; ( !0) the disorder may affect children or adults of
any age; (11) lack of H_LA-t>tv2 specLficity which is often
present in POH5;1:J and (12] appearance of new lesions
over time in several patients. 'Ihe reader should realize
that the presence of vitritis or iritis has been an important
requirement for inclusion of patients in reports concern­
ing MCP in order to exclude patients with POI-15, and that
some patients with M G ' and With active choroidal lesions
as well as multifocal scars may have no vitreous cells.
M .2 I M u llifo c a l c h o ro id rtis a n d p a n u v e itis ( p s e u d o ­
p r e s u m e d o c u la r h is to p la s m o s is s y n d r o m e ) ,
Л - С : Th is 3 1 -y e a r-o ld w o m a n h a d а й -у е а г h islo ry o J lo s t
o l v is io n 5л Ihe riyh l сущ c a u s e d by suEifoveal n e o v a s c u -
1 а п га И о л a n d re ce n t b lu rrin g o l v ini О л m ib e left e y e . In
a d d itio n lo w id e s p re a d m ul tilocal c h o rio re Lin a l scars a n d
vitrilis in b o lb e y e s , th e re w e re a c tiv e -a p p e a rin jj local c b o -
noidal lesions in the m a c u la , n a rro w in g o f [he retinal vessels^
a m o p tic disc sdairh'? a n d p a llo r in 1b e l|n t ey-e ' A a n d Ё>.
A n g io g ra p h y re ve a le d [hat s o m e o f [he c h o r iW E lin a l lesions
w e re n o n flu o re s c e n l e a rly 'C i a n d s ta in e d Ia lei. И е Г visu al
fields w e re m a r k e d ly c o tttfric te d a n d lh e eloclToreLinogr^nT
re v e a le d s e ve re ly a b n o r m a l ro d a n d -соле responses;. H e r
fa lb e r b a d s u b n o rm a l vis io n ibal w as a llrib u te d 1o w o rk in g ir>
a c o a l m in e . H e r fTuaresce.nl trujponem al a n tib o d y a b s o rp tio n
Lest w a s n e g a tiv e . It is cri interest I b at, c o in c id e n t w : ! h lh e
tinsel o f visual s y m p to m s , I b e pa Мел I b a d a je ju n o iie o s to m y
for o b o s ily a л d as a c o n s e q u e n c u lost 2 0 0 Lb (91 k g ). It is n o t
k n o w n w h e lb e r or n o t v ita m in A d e fic ie n c y p la y e d a n y ro le
in h e r ta p e Lo re lin a l d y s Lro p h v -lik e fu n d u s c h iin g e s .
0 - F : This T O -v e a r -o ld , hea lthy, m ild ly m y o p ic 1У£мТмп rio te d
b lu rre d v is io n in I h e I el I e v e o f I w e e k 's d u ra tio n . V is u a l a c u -
LEy in the rig h t e y e w a s 2 0 / 2 0 a n d in lh e ieft e ye w a s 2 Q /2 0 0 .
T h e re w a s a 1 -I- a ffe re n t p u p illa r y re a c tio n in the lelt e v e .
The right fu n d u s w a s п о т т а ! . A fe w v ilre o u s cells w e re pres­
ent in I he lefL e y e . There w e re m u ltifo c a l active gray lesions
in the m a c u la a n d ju xta p a p illa ry area ( O ) as w e ll as a te w
in the p e rip h e ra l fu n d u s . A n g io g r a p h y re p e a le d lale sta in in g
o f m a n y ol ih e s e le s io n s. M e d ic a l e v a lu a tio n lo r e v id e n c e ol
system ic disease in c lu d in g h is to p la s m o s is w a s n e g a tiv e . Th e
d ia g n o s is w a s c h o rio n itin ilis a n d o p lic neuritis o f u n k n o w n
ca u se. iy s L e m ic anti s u b -T e n o n 's s te ro id * w e re g iv e n . l\ v o
inonLhs later vis u a l a c u ity h a d im p ro v e d lo 2 (1 / 7 0 . M o s t o f
i!ic■ lesions .i :o i /:ri‘ : c-х-- . n :i\4- ■!■ . к ш г к :е п n to m b s I,Лег
she r-elurned b e ca u s e o l vis u a l loss in th e left e y e c a u s e d b y
sen jus d e la c h m e n t o f Ih e m a c u la I ha I re s o lve d s p o n la n e -
O Lb ly . N i r c \ч‘ .^!'s Inter I b e riLjhl :- :r ■.v.i-. n m m I. I hi' u-
i tv in the I ell eye w a s 2 0 / 2 0 0 . T h e r e w a s e n la rg e m e n t a n d
h y p e r p ig m e m a tio n o f th e c h o rio re tin a l sc.ars., a n d several
a tro p h ic scars Ia n o w , F.i w e re e v id e n l in areas o f p re v io u s ly
n o rm a l re tin a .
G - L ; This y o u n g w o m a n e x p e rie n c e d rap id o n se t o l loss o f
te m p o ra l lie ld a n d p h o to p s ia in h e r ritihl e y t;. The fu n d i w e re
n o rm a l LC>. Itie g ra y spot ^arrow ) in С is an a rtifa c t. Th e
s c o to m a p a rllv re s o lve d w ith in sevtiral m o n th s , p rio r to h e r
d e v e lo p in g loss o f cunlral vis io n a n d an e n la rg e d b lin d sfK^t
in the left e y e thaL w a s associate d w ith m u ltip le a c tiv e c h o ­
rio re tin a l lesion s IH a n d II. The d ia gno sis w a s punc tale 1плег
c h o ro id itis . 'Six m o n th s later s h e d e v e lo p e d b lu rre d v is io n
in the ri^ b t e ye associated w ith m u ltip le foci o f pa race ntral
c h c rio re Lin iliv Ijj. S h e stion d evelopjed e v id e n c e o f s u b ro lin a l
n e o v a s c u la r iia lio n in ih e m a c u la r area o f h o Lb еуеь (К a n d L :.
il? ,ind t irdMVi
■
_____________
.-■
■■ - ■
In fJa in m a b n rv D is e a s e s o f th e M e lin a
features of MCE’ similar to Р О Щ include punched-out
peripheral and posterior pole chorioretinal scare lhal are
occasional]!y arranged in a curvilinear pattern aL the equa­
tor, jujct^ipap:L]ar\- scarring, and the frequent development
of" jufcLapapillary and macular subretinal neovasculariza­
tion (E'igures 11.21 and 11.22].JQ5j2L<,,i]S Gass has seen ihree
children with M CP in association with bilaleTal pars plana
snow-bank exudation (see E'igure il .43|-J_).''"' 'lhe cause
of MCP is unknown. Features of M CP different from viti-
liginous retinochoroiditis include: [ l j lhe punched-out
nature of chorioretinal scars; (2) a tower median age (33
years); (3) a greater frequency of unilateral disease; (4) a
greater frequency of panuveitis; (5) a lower incidence of
optic disc pallor, nyctalopia, color vision deficit, and elec-
troretinograpbic abnormalities; (ft) a greater incidence of
visuaE loss caused by choroidal neovascularization; and
(7) lack of JEIA-A29 specificity. The fundus of patienls
wilh uni lateral involvement, in MCP may simulate I hat
in patients with diffuse unilateral subacute neuroreti­
nitis [see pp. 864-Й72). Visual loss in the latter disorder
is usually una&sociated with subretinal neovasculariza­
tion and is more frequently accompanied by pallor of lhe
optic disCr narrowing of the relinal vessels, and a mark­
edly abnormal EiPG. Multi focal choroiditis may occasion­
ally be a manifestation of sarcoidosis. Elersbey et al. found
focal granulomas on blind biopsy of lhe con|uncliva in a
group of patienls over 50 years of age with a fundus pic­
ture of pseudo-POMS and no olher manifestations of
sarcoidosis/11:
PU N C T A T E IN N E R
C H O R O I D O P A T H Y ___________________
Watzke and associates1'11, and Morgan and Schalz'^1,
reported a syndrome characterised hy the following: (1)
moderate myopia, blurred vision, photopsia, and sco­
tomata in women; (.2) multiple, yellow-white lesions of
the inner choroid and retina that are largely confined lo
tbe posterior poler and lhal after resolution leave atro­
phic pigmented scars simulating those in POIES [E'igures
11.21 !>-].): (3) frequent serous detachment of the retina
that resolves spontaneously; [4} no signs of vitritis or
anterior uveitis; (5} both eyes affected in most patients;
(6) negative histoplasmin skin lest (70%); (7) choroi­
dal neovascularization in 40% of eyes; and [8] relatively
good visual prognosis, with one-half of eyes retaining nor­
mal acuity. Doran and I Lami E t o n presetiled four similar
cases. 'Ihe macular lesions lend lo be arranged in a linear
or branching pattern in some cases {1-igure ! 1.2311—L).
figure 11.21 (D ) depicts such a paltern in tbe left eye of
a 30-vear-old myopic woman who also had mild vitritis
and a few peripheral chorioretinal scars in Lhe right eye/0''
lhe left eye was normal. Ibis patient, and others seen
by lhe author, suggests that the two syndromes [ГЕС and
1 1 .22 M u l t i f o c a l c h o r o i d i t i s a n d p a n u v e Elis ( p s e u d o ­
p r e s u m e d o c u la r h is to p la s m o s is s y n d r o m e ) ,
A —I : Tin is h e a llh y 3 9 -y e a r-o ld w o m a n e x p e rie n c e d flo a ty rs
a n d b lu rre d v is io n i r th e right e y e . H e r V isu a l a c u ity w a s
2 0 / 2 0 0 . T h e re w e re 1 + сеИн in lh e a n te rio r t h u m lw i ,;n d
2 + t o lls in lb e v itre o u s . T h e r e w a s m ild p u p iIle d e m a a n d
c y s lo id m ac-ulnr e d e m a i.Aj. tn Lne e q u a to ria l area for 3 fjO
Lnere W e re h u n d re d s o f va.riat]dy sizled, ro u n d , th o r io r e L i-
nal scars IB Hind C l . A n jiio jjra p h y ftfV e a le d c y s lo id fn a c u jd r
e d e m a a n d p a p ille d e m a i l J ) . T h e re w a t late staining a r o u n d
s o m e Dl Ifte p e rip h e ra l lesions IE a n d F>. T h e left e y e w a s
fid t m a L The s c o Lo p ic e le c lr o r e tin o ^ u p h ic responses w e re
m o d e ra te ly a b n o r m a l in the гщ Ы e y e a n d b o rd e rlin e n o rm a l
in llie left e y e . O v e r the пек I b 1/2 yearn sh e e x p e rie n c e d
fu rth e r kres ol v is io n in Ih e d ^ b t n \ e related lo siibfltffifral
n e o v a s c u la r iza tio n , lie fo re n o tin g floaters in th e left e y e , A l
lh al lim e V isu a l a c u ity in the rijijht e y e w as 2 0 / 2 0 0 a n d In Ihe
loft e y e w a s 2 0 / 1 5 . T h e re w e re v ilr e o u s c e lls in b o lh eyfis.
SEw h a d a d is c ifo rm scar Fn lh e ri^hl m a c u la -.til. There w e re
m a n y foca l cEw jrioretinal lesion s, н(ж_,с! o f ^vhi-rh I'p p m r e d
active in the p e rip h e ry o f Ihe letl e y e an ti Lj. A n ^ io ^ r a p liv
re v e a le d le a ky c a p illa rie s rn lb e o p lic d is c a n d retina o f
b u lh eyes.
| - L : Th is 3 1 -y e a r-o ld w o m a n h a d a I - y e a r h islo rv ol e p i­
sodes o f b lu rre d v is io n a n d p h o to p h o b ia in lb e left e ye .
V isu a l a cLiily in lh e i i j^hI e ye Mffls 2tV2(> anti in lh e left e ye
w a s 2 Q /2 0 0 . lh e ri|^bl fu n d u s a n d vitre o u s w e re n o r m a l
e x c e p t fo r m ild p erip ap iEEary s c a rrin g (j^L In Lhe left e y e I here
w e re J + v itre o u s ce lls; m u ltip le foca l cEiorroretinaL scars,
s o m e ol w h ic h w e r e steElatej a n d a s u b lo v e a l n e o v a s c u la r
m e m b r a n e K :. Te n m o n th s later, lEw vis u a l a c u ily in Lhe Eefl
e ye w a s c o u n lin ^ finders. a n d there w a s m assive suljretina l
fjbrosis I i. T h e ri^hl e y e w a s u n c h a n g e d .
M CP] are probably the same disorder or have a similar
pathogenesis.'" 'lhe presence or absence of vitreous cells
in these paLients is probably a function of the size of the
area of the fundus affected, '['hose with lesions confined
lo the posterior poEe (P IC ) are less likely Lo have vitreous
cells than those with widespread lesions (MCE1}. Once the
aclive lesions in both of Lhe&e syndromes become inactive,
and the vitritis and iritis resolve in the case of M CI3, the
fuLidus picture in many of Lhese patients becomes indis­
tinguishable from those with E^OIIS |usL as the absence
of viireous cells does not entirely exclude (he diagnosis of
MCPj likewise, the presence of vitreous cells probably does
not completely eaclude POLLS. Sub ret inal/choroidal neo­
vascularization can occur during the active phase of cho­
roiditis (figure n ^3A -{£ jatT or in a scar. Systemic steroids
used to treat the acule lesions may cause regression of the
neovascularization (Figure 11.23Л-С). En those eyes with
choroidal neovascularization occurring in inactive scare,
intravitreal bevacizumab is successful in causing regres­
sion. Pholodynamic Lherapy was used prior to intravitreal
antivascular endothelial growth factor agents and was rea­
sonably successful.
992
Hr
Some patients wilh MCtt and [’’EC develop prominent
subretinal fibrcj?vis in the vicinity of the focal choroidi­
tis (E-igure IL.22J-J.}. This process of reactive fibrosis may
be limited Lo small isolated areas around Individual cho­
roidal lesions or may foitn a la rg E confluent inter! aci tig
network or plaque of sub retinal fibrous I issue, ellher in
Lbe macula or in Lhe peripheral fundus. 5till others may
develop massive widespread fibrous tissue mounds a n d
severe visual loss. (See Figure 11.32 and discussion of mas­
sive SR fiJ1?!frJlS The eliology, pathogenesis, and natural
course of M CP and P IC are not known. liedem ati found
serologic evidence lo suggest lhal Ipsteln-Karr vims might
be a causative factor.J : '^ lhis could nol be confirmed by
others/' -'l!
The multifocal features of these pseudo-L:0 1lb disorders
have obsmred the fact lhal some of these patients develop
Eaige visual field defects that are usually overlooked, and
that are not explained during the early stage of Lhe dis­
ease by fundus changes [Figure IL.21C-L.}. These defects
are probably caused by acute damage to Zones of the reti­
nal receptors that may or may not recover function. lhis
Eoss of function may be confined to one or Lnore small
zoneSj particularly surrounding the optic discr or Lo large
peripheral /ones. E.oss of retinal receptors in large areas of
the fundus is responsible for the narrowing of the retinal
blood vesseEs and alterations in the R P t that may slmu-
Eale retinitis pigmenLosa in some of these patients. I his
occult phase of these pseudo-POM 5 disorders is similar to
thal Which occurs in patients with AZOOR,. M E:\VDS,- and
acute idiopathic blind-spot enlargement and Is со Llec Lively
termed AZOOR complex disorder/'1 [See previous discus­
sion of ME;WEDS and A 2 0 D Щ
Uncertain at this time is the frequency wilh which
patients who have pseudo-P O i($ develop recurrent epi­
sodes of new lesions or visual loss (i E to Lj, other than
that which may occur from delayed development of
sub retinal Lieovascularization at the site of a focal scar.
Although the author has observed delayed involvement of
Lbe second eye for up Lo Ю years, most of these patients
experience a single acute or sub acute event lasting for sev­
eral months in one or both eyes, and they are unlikely
to have a recurrence of active disease in the same eye
thereafter.
The predilection for pseudo-E’OJ IS, AZOOR. M EWD£ f
and acule idiopaLhic blind-spot etiiargejnenl lo occur pri­
marily in women; the primary locus of the disease in these
И .2 3 P u n c ta te in n e r c h o ro id o p a th y ,
A - G : A 2 J -у т л r-ol d o Lh e n v is e h e a llh y s c l № r p re s e n te d № i4t
m e La m o rp h o p s ia and v is u a l d e c lin e Lo fJ rn his ri^hl eVCL
Several p u n c l.a le w h ite le s io n t w ere p re se n l in b o th fo v e a s
a-ssocjaLed w i lh a fFeck o f h m in r r b a j’ o ir lii-ь i ig hl e ye
i A a n d SJi A n g io g ra m revea led ьё&ёгй! EiypetflkjOrescem t dels
LhaL s ta in e d la te a n d a sm all s u b lo v e a l c h o ro id a l n e o v a s c u la r
in c m b M n o Cnrt^fcterii w ith a d i v e [ILrtc tu a fe jn n e r c h o ro id itis
lesions (C."—£ ). O-raL steroids a l 5 0 m y. w e re slarLed, [he v is io n
g ra d u a lly im p r o v e d , lb e lesions tu rn e d in a c tive i.J-j, a n d .p ye r
lh e n-estL 3 m on Lh s The c h o ro id a l n e o va p fifrla r m e m b r a n e b a d
iej>ressed i'CJ 1 a n d lh e v is io n rfecovetien to 20/25 .
H-L: I h i t 2 4 -y e a r-o id re c e n lly p re g n a n t m y o p ic w o m a n
d e v e lo p e d M e ta m o r ip S n p ^ i in h e r righl e y e a n d a v is io n
c h a n g e Eo 1 0 / 3 0 righl e y e a n d 2 0 /2 0 — lefL e y e . A fe w v itre ­
ous cells w e re present in her right e y e a sso ciate d w iLh Lw o
y e llo w vvhrLe c h o ro id a l/o u le r retinal lesions on Lhe гii^JnI .;n d
o n e o n Ihe lefl [H a n d E). A d ia g n o s is o f p u n c tu a te in n e r
th o r a jn ljis w as m a d e a n d she rece ive d oral slero ids after ai:
ajTgldnta frt c o n firm e d a b s e n c e o f CfiorniFdal n e o v a s c u Ja ri^ a -
Liun. H e r v is io n im p ro v e d to 2 0 / 2 0 in b o th eye s. O v e r Lhe
n e xl 2 years sh e d e v e lo p e d several n e w m a c u la r lesions (|)
e v e ry Lim e h e r p re d n Ls o n e w a s re d u c e d lo th e 2 0 -m g ra n g e.
O r a l m e Lh o lre xa te w a s a d d e d after a d v is in g aga inst fu rth er
p re g n a n c ie s . She c o n tin u e d h e r fo llo w -u p e ls e w h e re a n d
le lu rn e d 3 years la lcr w iLb several m o re lesions in EjoLh e ye s
IК a n d t . She w a s m a in ta in e d o n m y c o p b e n o la le т о Е й :1
a n d m o Lh o lre s a le ап-d h a s re m a in e d s t a q i ilu o r e s c e in
a n g io g ra m s J!l n o Stage. re v e a le d c h o ro id a l n o o va sc u Ja ri ha­
lie r in e ith e r e ye .
disorders at the level of Lhe reLinal receptors and pigmenl
epithelium; and the similarity of the pathologic changes
in eyes of patienls wilh mullifocal choroiditis and massive
SRE-' lo experimental uveitis induced in primates by inier-
pholoneceptor retinoid-binding protein suggest lhal auto-
immunlly plays an irnporlam role in Lhe palhogenesis of
these disorders2D7j22J (к е E'igure L1J2). '['he experimental
]nodel of Hi rose and cowo rkers'' J demonstrates some of
the clinical features of pseudo-lnO H Sr including mu II efocal
choroidal lesions. Lhat histologically were focal granulo-
]nas associated wilh widespread retinaE receptor changes.
Their model demonstrates that antigen localized specifi­
cally iл the retina may cause widespread changes in the
retina] receptors and also may initiate im mu no pathoge­
netic changes in the choroid as welE [see discussion later)
(I'igure 11.3213-1).
Puncfiih: In u rr Chcriiiidi?paik\j 993
ACUTE MACULAR
NEURORETJNOPATHY
llos and Deulm an'"" described peculiar clove deaf, wedge­
shaped lesions thaL develop in Lhe macular region of
both eyes of young patients who complain of rapid loss
of central and paracentral vision, usually following a flu-
Ejke syndrome (i-'igure И .24А-С).1" 22'' 2ii lhe coIof of
Lbe fundus lesions Is dependent upon lhe pigmentation
of the fundus and varies from grayish lo reddish brown.
Visual anillv is usually reduced tc 20/30-20/40. I ’hese
palients can outline precisely on (he Amsler grid negative
scotomala corresponding wilh lhe fundus lesions (I'jgure
11.24G). In paLients wilh lhe full-blown disease, dark,
flower petal-shaped lesions are present In lhe central mac-
utar region [Figure П.24АГ E, and H j. In olher patient^
however, the lesions are less prominent and may consisL
of ntulliple oval Lo round, faintly pinkish paLches in lhe
central or paracenlraI region (I'igure 1I.24IJ and hj. Ihey
are seett better wilh red-free light but. most easily with
scanning laser ophthalmoscope [Rgure 11.2511)."4 " '1
These lesions appear lo lie at the level of tbe outer reti­
nal Eayers,J J *,2i rather than the superficial relina,
as suggested by bos and Deutman. O C I and multi­
focal ERG demonstrate involvement of Lbe photoreceptors
and ouler nuclear area, lhe inner segment-ouler segment
junction is disrupted with ihinning of lhe correspond­
ing outer nuclear area [ligure 11.251).' л -^ Averaged
waveforms from the affected areas are reduced compared
to adjacenl areas of normal function.J b Only one eye may
be involved. One or iwo small superficial, Tame-shaped
retinal hemorrhages may be present (higure M..24BJ.'' v“
'ihe retinal vessels and optic disc are normal. There are
no cells in the vilreous. Huoreseein angiography in well-
developed cases (ihows a fainl hypofluorescence corre­
sponding wiLh lhe lesions (L:igure 11.24С and 11. L'ransienL
choroidal ischemia may have a Able in some cases [I'igure
11.25]. Aulofluorescence imaging shows no changes cor­
responding to the lesion (Hgure 11.25G). Resolution
of lhe lesions and improvement in acuily and field loss
occur slowly оч'ег a matter of weeks or months [I'igure
11.241').■'■ ' Ш scotomas in some cases may be prolonged
for many months or y e a r s . OCT shows sharp loss of
photoreceptors (I'igure 11.2r>l Lesions identical Lo acule
macular neurorelinopathy have occurred in palients with
M EW D5 and acute blind-spot enlargement.M,i,lu
Although most of these palients have noted lbe onset of
symptoms within a week or two following a flulike illness,
olhere develop identical-appearing lesions and acute visual
loss after receiving intravenous injections of sympadioml-
tnelics''1' or iodine-containing conLrasl agents, 4, or follow­
ing anaphylactic shock after a bee sling [figure ] ] .24G-I).1'
!f examined immediately after the visual loss following Lhe
injections the lesions may have a gray-while appearance tbal
is difficult to discern, and later become darker in color simi­
lar to ligure 11.25. Acute macular neurorelinopathy has also
been reported in association with oral contraceptives, trauma,
history of headache or migraine and postpanum hypoLension.
M .2 4 A c u t e m a c u la r n e u r o r e t i n o p a t h y
A —С : T h is 3 1 -y e a r-o ld b la c k w o m a n gave a 2 -w e e k h is to ry
of a fl.ilik e s yn d ro m e 1 b e fo re lh e e n s e ! o f blu-rrud vis io n ,jn d
paracenLraE s c o Lo m a la in b o lh e y e s , i h e h a d s o m e p a ir o n
o c u la r m o v e m e n t. H e r v is u a l a c u ily w a s 2 0 /5 0 b ila te ra lly .
N o L e lh e b m k f i d d ark a reas in lh e m a c u la * re g io n o f berth
eyes ( A a n d tt) A n d the s u p e rfic ia l reLinaE h e m o rrh a g e s u p e -
:io r lo the Й а с и 1 а in the le!1 e y e 'д г п ж , H-.l A n g io g r a p h v
re v e a le d o n ly m ild d ila tio n o f the retinal ca p illa ries s u p e rio r
to Lhe m a c u la . T h e re w e r e n o o th e r cha ng e s in (he fu n d i.
F iv e m o n th s I filer visuaE a c u ily im p ro v e d to 2 ( 1 3 0 a n d J - l .
T h e a p p e a ra n c e o f the m a c u la h a d re m a in e d e s se n tia lly
ui к b a n g e d . The p a lie n l w a s lost Lo fo llo w -u p .
D - f : This 2 b -y e a r -o ld w h ile w o n iiin n o te d m u ILi p ie p a ra -
cenlraL s c o to m a ta A n d p h o to p s ia in Ihe left e y e u n a s s o c ia te d
w ith a v ira l-lik e illness. "Ih e v is u a l a c u ily w a s 2 0 ^ 5 . S h e
b a d m u lt if jlti. s m a ll, v a r ia b ly s iz e d , d a r k , r o u n d spots al lb e
level o f the o-uLej re tin a : [ Л and Ы . These c o rre s p o n d e d w ilh
d ense s c o Lo m a la e v id c n l tin lb e A m p le r I’ ri.cl. A n g io g ra p h y .
e le c Lro re tin o g ra p h y , a n d e le c Ln o -o c u fo g ra p h y w e r e n o r m a l.
These spots a n d the s c o Lo m a La fa d e d o v e r a p e rio d o f m a n y
m o n th s . V is u a l a c u ity 7 years later w a s 2 1 У 2 5 IF I.
C - l r Ln O c t o b e r 19flt± this heaLLhy 2 7 - y e a f- o ld w o m a n
n o te d m u ltip le p a ra c e n tra l n e g a tive sc o to m a s in the right
e y e . A n o p to m e tris t n o te d m u ltip le "h e m o rrh a g e s " in the
right m a c u la . F iv e m o n th s later the s c o lo m a s p ersisled
a n d w e re e v id e n t o n A m s le r g rid testing ■.C ]i. V is u a l a c u ity
was 2 Q /E 5 b ila te ra lly. F u n d r is O g p it e x a m in a lio n re v e a le d
a p a lle rn o f o u Le r relin a ! re d -o ra n g e lesions ( H ) that c o rre ­
s p o n d e d w ith Lhe A m s le r g*id L'b a n g e s . The left e y e W as nor­
m a l. A n g io g ra p h y re v e a le d m in im a l c h a n g e s LlJ. W h e n she
re lu m e d b yearn la te r the sc o to m a s a n d visual a c u ity w e re
u n c h a n g e d but lh e fu n d u s iesjDrts w e re n o lo n g e r presen t.
] a n d ftr This h e a llh y 2 Й-y e a r-o ld w h ile w o m a n h a d u terine
N e e d in g after a n e le c tive ce sarea n d e live ry. S h e re c e ive d 1 0
units o f o x y to c in (P ilo c in l a n d e p in e p h rin e liy in tra ve n o u s
p u s h , She e xp e rie n c e d s evere h e a d a c h e , e le va tio n o f b lo o d
pressure, a n d e xlra sysloles Lhal w e re c o n tro lle d w ilh intra­
v e n o u s lid o c a in e a n d S o d iu m P e n to th a l a nesth esia. O n
a w a k e n in g she n o te d Central scotom ata! a n d h e r vis u a l a c u ­
ity w a s 2 0 / 2 0 0 . A "c h e rry-re d spot a n d m a c u la r e d e m a " w e re
d e s c rib e d . H e r v is io n im p ro v e d o v e r lh e печ! fe w dniys. Six
w e e k s later h e r visual a c u ily w a s 2 Q ; 2 0 . S h e had paracenlral
sto Lo m a La a n d Ihe typica l p ic tu re o f a c u le m a c u la r n eu rore t:-
n o p a th y in b o th m a c u la r areas (I). T h e reddish lesions in v o lv e d
the o u te r retina a n d th e y w e re slig h tly h y p o flu o re s c e n t angco-
g ra p h ic a lly (K j. T h e s e lesions fa d e d a n d w e re associated w ilh
suErtle retinal p ig m e n l (/pilhelial ch a n g e s, Fiul I h e y a n d lh e ir
c o rre s p o n d in g scoto m a s w e re still e v id e n t 5 years later.
L: Th is 2 4 -y e a r-o ld w o m a n h a d a n a b d o m in a l c o n f u t e d
to m o g ra p h y scan p e rfo rm e d w ith in je c lio n o l 2 0 cc 6 f Loth al-
a m a le b ecau se o f e n la rg e d aEw Jom inal ly m p h n o d e s, p r o b a b ly
caused b y in fe c tio u s m o n o n u c le o s is . LJecause o l d c ^ e lo f>m enI
o f u rtic a ria , p a lp ita tio n s , a n d severe h e a d a c h e she w as g ive n
an in Ira ve nous in je c tio n tn 0 .2 cc ttf e p in e p h rin e 1 :1 0 0 0 a n d
5 0 m g o f H e n a d r y l. Ten hours later, o n a w a k e n in g sh e n o te d
sc o to m a s centraEEy. M a c u la r a b n o rm a litie s w e re n o te d . T h re e
w e e k s laLer h e r v is u a l a c u ily w a s 2 0 / 2 5 , riyb t e y e , a n d 2 0 /3 0 ,
fell e y e . ЗвдШаг red dish OLiter ifetinal lesions a n d c o rre s p o n d ­
in g scoLom as w e re presenl jn b o lh m ncuSas. These le tjo n s
w e re associated w ith slighl h y p o flu o re s c e n c e a n g io g ra p h i-
cally. Three m o n th s luler lh e visual a c u ity a n d fu n d i w e re
u iil h a r g e d . The s c o lo m a la w e re s im ila r Liut less d e n s e .
11J'rvd К Гг(лпO' HrimeLщ
Г.-1 i fromC tud k cjL,l! J1■
 The fundus lesions, when they are reddish in color,
may be mistaken for subretinal blood. Ih is may htive hap­
pened in the case reported by Weinberg and Nerney/"'
lh e milder forms of ihLb disease (1'lgure l\ Л4L^—Зг) may
be misdiagnosed as acute retinaJ pigment epilheliitis
since both diseases cause temporary loss of cenlra] vision,
usually in young individuals (see p. Й74). tiarly recep-
Lor potential changes may he evident electro retin ographi-
cally and may persist for many months."1' The pathology,
pathogenesis, and course of these pecuEiar macular lesions
are unknown. Cases of M bW DS and acute macular tteuro-
retinopalhy occurring in the same eye of 2 young Women,
Пг25 Acute macular neuro retinopathy (AMN).
1 hrs 2 i - y e a r - d l d u lh e rw is o b ^ l l h y ^ и т л л w o k e L ip w ith д
s u p e rio r p a ra c e n tra l defeat:! in h e r n ^ h t e y e . O n A m s le r f^rid
testing Iht1 lines .Were a b sen l in Lhe ared Ы (he fitfld d e fe c t,
i n e f l ^ u r i a p p r o x i m a t e l y 2 X 3e- F u n d u s A p p e a re d n o rm a l
iA . , h u t iht! retinal u n d c h o ro id a l c irc u la tio n s w e re b lo w
|J 1 - E |. S h e w a s n n oral c o n lra c e p liv e s Ihill w e r e d is c o n ­
tin u e d . T h e field d e fe c t persisted w h e n seen a m o n th later.
N o w a "b n u n jp u " flint. o lu ia Lio n w a s n o te d in her ftihduift c o r ­
re s p o n d in g to the s c u tm i.i i f : , w h ic h in best неел a n infra­
red in ^ a y m jj ( H , a rra w i a n d in v is ib le o n a u t o f l u o T e s c e n c e
i m a ^ i n ^ ( G ) . O p t ic a l c o h e r e n c e to m o g ra p h y s h o w e d lo s s o f
p h c M o r u c o p t o T i in- the л f i l l e d a r e a 1 1 a r m W .

a few weeks apart in one, and !>years laler in Lhe other,

suggest that they may share л common etiologjc agent,
l-'urthermore, photoreceptor involvement in these, and in
acute idiopathic blind-spot enlargement and A/OOK, sug­
gests Lhey may be related in their etiopalhogenesis."'' 1
lh e sharply demarcated reddish lesions corresponding
rather precisely to the visual field loss suggest that acute
loss of lhe retinal outer receptor elements and lo some
degree the inner receptor elements in sharply delineated
xones is responsible for well-demarcated zones of outer
retina] thinning that cause the reddish appearance of the
lesions. OCT demonstrates loss of photoreceptors corres­
ponding lo the lesion [E'igure 11.25 ]) 3'he mechanism of
this focal damage iis probably different in the palients who
develop this disorder following a viral-like disorder than
in the patients who develop It after intravenous injections
that usually contain sympathomimetic drugs. En the lat­
ter patients, either transient choroidal ischemia (figure
LI .25ti-E:J or a toxic interaction between the drug and the
receptor cells is a possible explanation for the damage.
Other causes of sharply defined areas of retinal thinning,
e.g., alrophy of the outer retina after resolution of Berlin's
edema;2^.2^, sjckle-celE hemoglobin macutar infarcts,1,"|J
cotton-wooJ infarcts,"4' and inner lamellar macular holes,
may produce reddish lesions bio microscopical ly. ■
HA RADA'S DISEASE M :i$> Vogl-Koyanagi-Haradti (VKH) syndrome.
А -I’ T h is 2fi-ye < ir-o ]d A f r i c a n A m e ric a n w c im a H ртоьеп.Еич!
P a tie n ts w ith H a r a d a 's dise a se , w ho ty p ic a lly are beav- W i t h h e a d a n + i e s . П Ё с к p a i n , a n d loss o t v i s i o n i n l i o t h e y e s .
[]y p ig m e n te d in d iv id u a ls , m a y e xp e rie n c e rtp id lo ss o f Bilrile fd l p o c krils of u ub rotin al flu id and c h o ro id a l fo ld *
v is it) it i n o n e o r b o t h e ye s c a u s e d b y s e r o u s re tin a l d e ta c h - w e r t f s e e n - Л , E3, a n d H i . H i n p o i n l f f i m r f l U B n E s c e n t d o t e I h a I
m e n t . 2^ -2 5 7 T h e d ise a se by d e fin itio n is b i E a l e i a l ; o c c a ­ l e a k e d d y e u n d e r t h e re 4 in a w e r e t e e n o n t h e a n g i o g r a m , t y p ­
ical o f V K H s y n d r o m e Lt! —t ' . O p l i c a l cu honEjnc."» l u m u g r a p h y
s io n a lly in v o lv e m e n t o f lh e s e c o n d eye г ш у be d e riv e d by
c o n f i r m e d liic j ft r e s e n c e o f sb b r e t i-пn1 f l u i d in b o t h e y t i s (F a n d
a fe w days lo a week S u b tle c h o ro id a l fo ld s m a y lie lh e
C l ' , j j h e r e s p o n d e d to o r a l s t e r o i d s w i t h r e s o l u t i o n o f E h e e x u ­
o n l y f i n d i n g in t h e f e l l o w eye. 'ih e s e m a y b e d e te c ta b le b y
d a t i v e d e E a d u n u n i s in b o t h e y tis 11). N o L d t l ie c h a n g e in t h e
Q C T as c o rru g a tio n s o f lh e R P h /c h o ro id and c h o ro id a l
c o l o r of l h e f u n d u s Lo a n ( j u n g e s u n s e t ^ l o w f[j.
th ic k e n in g if nol e v id e n t c lin ic a lly. There is. s o m e e v i­
dence th a t m a n y a ffe c te d b la c k s in lh e U S A have N a tive
A m e ric a n a n c e s try, w h ic h lin k s th e m lo an O rie n ta l
a n c e s tr y ." J l h e re i s n o sex p re d ile c tio n . S ys te m ic
m a n ife s ta tio n s su c h as h e a d a c h e , m a la is e r v o m i t in g , a n d
o c c a s io n a lly fo c a l n e u ro lo g ic s ig n s and s ym p to m s m ay
p re c e d e th e o n s e t o f v is u a l lo s s .'" '1 Jn iL ia lE y r n o n d e s c r ip t.,
y e llo w -w h ite areas o f e ith e r e x u d a te o r c o lo r c h a n g e in
th e К П : occur b e tie a th one or m ore is o la te d zo n es o f
serous re lin a l d e tac h m e n L (fig u r e 1 1 .2 6 A and IIJ. 'ih e s e
/ o n e s o fte n b e c o m e c o n flu e n t to fo rm a n e xte n s ive b u l-
Eou s s e ro u s r e lin a l d e t a c h m e n l th a t s h ifts w i t h p o s itio n ­
in g o f th e p a tie n l. In a fe w p a tie n ts , m u ltifo c a l, g ra y -w h ile
p a tc h e s at t h e le ve l o f lh e R PE s im ila r to , b u t Lets w e l l
d e fin e d th a n , th o s e s e e n in p a tie n ts w i t h A jP b J P P E r o c c u r
(fig u re s ll.2SL> a tid ]i.2 7 G j. Ilie c h o ro id m ay appear
th ic k e n e d and Ln som e cases- is a s s o c ia te d w ith broad
c h o rio re tin a l fo ld s (K ig u re I I .3 1 3 6 ^ -1 )." ^ lh e o p tic d is c
ty p ic a lly appears h y p e re m ic and s w o lle n . Ih is s w e llin g
m ay be w vere and a c c o m p a n ie d by hem orrhages and a
m a c u l a r i t a r i n s o m e cases. ( f i g u r e s 1 1 .2 6 G a n d U . 2 7 J ) . ■ :" ,
I n f l a m m a t o r y ce lls a r e i n v a r i a b l y p r e s e n t in lh e v itr e o u s .
Irid o c y c E itis m a y b e p re s e n t in s o m e ca^es. I n f l a m m a t o r y
in filtra tio n o f th e a n te rio r c h o ro id and c ilia ry body m ay
cause s o m e n a r r o w in g o f th e a n te rio r c h a m b e r a n d , in a
rare ca s e , a n g l e c l o s u r e g l a u c o m a . ' 1 , Ultrasonography
u s u a lly d e m o n s tra te s d iffu s e Low to m e d iu m re fle c tive
th ic k e n in g of th e p o s te rio r c h o ro id -s c le ra l w a l l . J : , , J f ' t!
У 1 -w e ig h te d sa g itta l s u rfa c e c o il m a g n e t ic r e s o n a n c e im a g ­
i n g o f L b e o r b i l is c a p a b l e o f d e t e r m i n i n g l l i a l t h i s t h i c k e n ­
i n g in V o g l - K o y a n a g i - l i a r a d a (VK JE) syn d rom e is c a u s e d
b y c h o ro id a E a n d n o ts c te ra l t h ic k e n in g .'''0 J V 1
 Fluorescein angiography may demonstrate (beat or
patchy areas of delay in choroidal perfusion (figure
1I.27EI). Many pinpoint and irregular areas of fluorescein
staining develop al the level of the RPiL (figures U.2(iti, C,
E, E K, and L, H in d II.27C, H, and Y. 11.2 SC and L>). Lhese
areas of fluorescence gradually increase in size and in
some cases form large placoid areas of hyperfluorescence
Lbat some Limes resemble cobblestones at lhe level of the
R1TL {Figfires 1L26C and 11.27b). Ih e subretin al exudate
stains wilh fluorescein during Lhe late stages of angiog­
raphy. OCL' demonstrates lhe subretiLial fluid, occasion­
ally loculation of lluid due lo high fibrin content, may
be seen [I'igure 11.2til:). Spinal fluid examination usually
reveals evidence of pleocytosis and elevation of the protein
Level. Although in л few cases the retinal detachment may
resolve spontaneously within several weeks or less, usu­
ally the course is prolonged. Intensive systemic corticoste­
roid therapy appears to shorten the duration of the retinal
detachment.2''0' ' ' J Use of immunosuppressive agents may
be required in patients with severe chronic disease. Varying
degrees of visual loss accompany Lhe RPJ: changes (hat
remain after resolution of Lhe detachment. Most patLectts
regain excellent visual acuity following their first episode.
Recurrences are common, bul lhe overall visual prognosis
is good.270-273
A variety of fundus pictures may develop following res­
olution of the retinal detachment. E’atchy loss of pigmeLit
from the underlying choroidal melanocytes as xvell as the
EPE may be evident after resolution of the detachment. An
irregular pattern of pigmented demarcation lines caused
by Lhe choroidal Lhickening may radiate ouL away from the
oplic disc and be scattered in Lhe peripheral fundus after
resolution of choroidal infiltration and prolonged retinal
detachment {figure П.26П and L). In some patients mul­
tifocal atrophic chorioretinal scars simulating that in viti-
Eiginous (birdshot) chorioretinopathy and POJES occur,
lhese lesions may occasionally be confluent and arranged
In a curvilinear equatorial pattern similar to that seen in
P O I3S and pseudo-1*0 hIS .'"1 In other patients a diffuse
depigmentaiion of the choroidal melanocytes occurs and
the fundus may change from brunette lo blonde or present
a "setling-sun, reddish glow" appearance [Figures 11.27A
and C- and 11,2tiH and K). Subretinal choroidal neovascu­
larization and optic disc neovascularization may occasion­
ally occur as a late com plication.'"1' ' ' 1" '' bcleromalacia
presumably caused by autoimmune attack on the intra-
scleral melanocytes may occur.■ ' a A smalt choroidal
osteoma developed in otie palienL seen by Cass (I'igure
11.27D).
The serous delachment in И ara da's disease is caused by
diffuse granulomatous inflammation of the uveal tract.,
with a prepOLtderanсe of lymphocyles, plasma cells, epi­
thelioid cells., and occasional giant cells with evidence
of pigment phagocytosis.^2-251'^ 3,275-211 'Ihe inflamma­
tory cell reaction usually involves the choriocapillaris.
Sub pigment epithelial plaques of inflammatory cellu-
Ear exudate may be the cause of the yellowish subretinal
I •:л7 Harada's disease.
A-С: Th i-s 3 0 -y e a f-o ld L.alLn w o rn a n vvilli h e a d a c hes a n d slifl
necfc K i d b j lateral EjuMous reLinal d e ta c h m c n l IA 1. N o t e p in ­
p o in t as toeff as p itie d id areas o f late s La im n y '.hSl. C , S^V e fl
m o n Lh s a fte r re s o lu tio n o f the d e La c h m e n L. E3olh fu n d i b a d
t h a n d e d fm m a b ru n e LLe lo a re la tive ly b lo n d e , re d -n ra n ^ e
("surcseL g l o w 17} col cm i O .
I .t - F r This- 1 1 -y e a r-o ld La i in ^irl е х р е п е п й М b ila te ra l riBtftial
d e La th m e n S s setbcictftry Lo fefei'ada's di-seasn a n d ал п га л ^ е
subnet ina I Is sib n that u Ltra s u n o g ra p b ic a llv a p p e a re d to b e a
c h o ro id a E osLeom a (a rro w s , D ) . A n jjiu y r a p h y re v e a le d m u l­
tip le p in p o in l le a ks a n d flt^ m s C e in .‘fla m in g o f lh e s-uEjnj-l i na I
rk iid in b o lh eyes ib a n d J . Th e d e ta c h m ertts re s o lve d a fle r
c o rLic o s te ro id Irealm u-nL. W h e n sh*- netuined s e v e S l years
la lu j h e r v is u a l a c u ity wan n o r m a l. Th e usLeom a in lh e Eefl
e ye a p p e a re d Lo h a v e d e c re a se d i r s iz e .
fc-L: U n u s u a l p fe s e n La lio n o f H a r a d a ’s disease in a .14 -у е л г-
o ld b la c k m a n w h o p re s e n te d w ilh h e a d a c h e a n d mi id vis u a l
lo s t ass(d ia le d w ilh u p lic disc s w e llin g m a c u la r slair serous
rnlinal d e la c b m e n l LbaL w as la rg ely ( .o n fin e d to Lhe m a c u la ,
autl m u llip ie ill-d e fin e d w h ite sfioLs '.arro w s: at lh e level o f
lh e relin a l p ig m e n t ер-il h e liu m :F it3t I d : . U ltra s o n o g ra p h y
re ve a le d d iffu s e th ic k e n in g o f th e c h o r o id nimd no a b n o r-
m aEity rjf ih e o p lic d is c . A n ^ io ^ ja p h y s h o w e d IhaL the w b ite
spoLs b lo c k e d cb ofu -ida l flu o re s c e n c e (a rro w s f a n d sLained
la le ( H a n d 3). S c v c ia l w r a k s la lcr ihuTe wa-s iH c re a s w f S w e ll­
in g o f Lbe o p lic d iscs a n d fu rth e r retinal d e La c h m e n L L j - L f .
N e u r o lo g ic e v a lu a Lio n was n o r n ia l. A lie Г iie a l m eul w ilh
p r e d w M w e ., Я О гп ^ d a lly , Ihe o p lic d is c a n d relina l c h a n g e s
re s o lve d but irreg ular KF'b a tro p h y re m a in e d .
lesions and Lhe placoid areas of lale staining that occur
in some patients wEth this disease. In one patient's eye
wilh the active stages of the disease the choroidal infil­
trate was composed of predominantly T lymphocytes and
HE A-DR + macrophages and, in addition, no ndendrt Lie-
appearing CD I -(leu-6)-positive cel!s.jH': A 1-cel I-media Led
immune reaction to ocular antigens seems to play a maior
role in VKH as well as sympathetic uveilis.J ),2fi2 Jnomata
and Sakamoto studied the hislopathology and immuпо­
ра tbology of iwo eyes of 2 patients wilh "sunset” fundus
32 months and 7 years afler resolution of the subretinal
fluid.-^ They found marked loss of the choroidal mela­
nocytes and scattered infiltration of Lhe choroid wilh 1
and В lymphocytes. Although a few patients may
have patchy, grayr subretinal lesions that have suggested lo
some authors an etiologic reIalio ns hip to AFMeFBy Cass
t>elieves there is little evidence that ihey are manifestations
of the same
A few patients with Harada's disease eventually develop
severe anterior uveitisr alopecia, poliosis, cutaneous as
well as perilimbal vitiligor and dysacousis (V'KFl s\rn-
drome),-33^2^ -26,5 ЧЪе similarity of the dinical and his­
topathologic findings in this disease, sympathetic uveitis,
and experimentally induced uveitis suggest that autoim­
munity lo melanin is important in the pathogenesis of all
lhree/j!:!i-",J -
J00-''1VKH has occurred in siblings and mono­
zygotic iwins.-^-*"*
1001 Ziuzin *ufwi>i-)
 The Revised Diagnostic Criteria for VKH disease
was established at the lirst. International Workshop on
VogtKbyanagl-Harada disease. According lo this criteria,
VK1 i disease is divided into two subgroups, incomplete
VKH and complete VKH disease; incomplete VKH disease
Involves ocular finding and either neurological/auditory
o f integumentary findings, w h i l e complete VKI-1 disease
includes ocular, neurological/auditory, and integumentary
findings/1 "''1
Corticosteroids are the first line of treatment; they
should be started at a fairly high dose of 1-1.5 mg/kg
body weight depending on lite severity of the disease,
imntunusuppressives are added if there is difficulty in
tapering lhe steroids, or iit those eyes that shoxv recur-
rences.J " ' bleroids should be tapered very sLo\'.,ly and a
Low dose maintained for up to 6 months or longer. Larly
withdrawal сHouses recurrences and secondary complica­
tions such as angle closure and pupillary block glaucoma.
'lhe differential diagnosis in Harada's disease includes
severe idiopathic central serous chorioretinopathy (Kigures
З.Ш and 3.IIJ.. acute leukemia (ligure 14.35A-L), meta­
static carcinoma, uveal melanoeyLic prolife rat ion associ­
ated wilh systemic carcinoma, idiopathic uveal effusion
syndrome (see figures 3.64-3.66), and benign reaclive
Eymphoid hyperplasia of the uveal tract, lichography in
Harada's disease shows low-reflective thickening of the
choroid t h a t may be helpful in differentiating it from more
highly reflective thickening caused by idiopathic uveal
effusion and diffuse metastatic carcinoma- or thicken mg
of the choroid caused by choroiditis as a result of poste­
rior sclerochoroiditis, which is typically associated with an
ecbolucent^one in the episcleral area (see p. !016).
Orientals with H1A-DR4, -DRw53, and -DQw7 and
racially diverse American patients, often with Native
American descent, and widi IIIA-DK4 and -DQw3 and
-DRw53 are susceptible lo у К Л 25^ 7^ *
Harada's-Like Syndrome in Children
ii i lateral
secondary retinal detachment in relatively young
and brunette adults is the hallmark of Harada's disease.
11.2* Vogl-Koyanagt-Harada syndrome - asymmetric
presentation,
Л - C : This- p a N e n l p re s e n te d w ilh y y in p lo m s ir* tb e rijjht e y e ,
w h ic h s h o w e d several p o c k e ts o f a u lir d in .il flu id l A l, w h ite
the lefl fu n d u s s h o w e d m :ld r h o H iid n l i h k kenirtg fln d super-
I it ini t h o r i(n o tin g I fold s Ф ) . A n ^ i o ^ a m re v e a le d h y p e r flu o -
rescent d o ts that lea ked fluid IС find ]> .l O p t ic a l c o h e re n c e
to m o g ra p h y s h o w e d p o c k e ts o f s u b re tin a l a n d intraretinal
flu id (in the ri^hl a n d 4'almosl n o rm a l retinal c o n to u r on the
left 'it a n d F l* F o l k i w i o ra l p re d n is o n e the serous delaich-
т е п ! re s o k 'e d w ilh m ild c h o ro id a l f o l d s 1C l
H— Ji This 1 7-у е п г-о к 1 L a lin w o m a n With bilateral b u llo u s
re lirn l doLriehm enlj; p re s e n te d w ilh m u llip le ill-d e ffo e d w h ite
[estons larrow ^.. hi I л I the level о I Ih e R ^ h . A n tffc flP b p h y
re v e a le d e v id e n c e of m u ltip le p in p o in t aruas erf le a k a g e in
bcuh eyes U a n d Jl a n d a lo ca l ant;a o f serous d e la c h m e n l o f
Lhe R P E in Ihe left e y e I'a rro w j. 7tie d e ta c h m e n l in b o th e ye s
c le a re d p n jrrip lly a tle r Hyslem it: e o rtic o s le rn id tre a tm e n t.
К -M l B ila te ra l b u llo u s retinal d e ln o h m e n l ini } c>-year-old
VWtimart w iLh Н а га da's disease associated w ith u llra s o n o -
g ra p h i£ e v id e n c e o f ih ic k e n in ^ o f Lhe c h o r o id . N o te p in p o in t
leaks in stereo a n g io g ja m s (L and Ml.
l A - G . i- c ju rljf- :/ Ы l.im L 'i V ;in < le r. I
In sojne cases, however, children are affected and only
one eye may be involved.Jl>y 300 Serous retinal detaclunenl
confined lo the posterior pole of one or both eyes of chil­
dren may be associated with mtld ocular pain, thickening
of the posterior choroid, anterior-chamber and vitreous
intlammalory cells, and fluorescein angiographic evidence
of multiple pinpoint leaks al the level of the RTH-i..J ""- '0:
Ihey may or may not have syslemic signs or symptoms.
The localised detachment may resolve spontaneously or
respond rapidly to oral corticosteroid therapy. It is the
author's clinical impression that children wilh this clini­
cal piclure in the absence of evidence of syslemic disease
respond quickly lo therapy and have less chance of expe­
riencing a recurrence than adults wilh I larada's disease. It
is possible this is a mild, self limiting posterior sclerilis in
one or both eyes of some of these children.
SYMPATHETIC UVEITIS
Patients who have sustained a previous penetrating ocu­
lar Щиту, whether accidental or postoperative, affecting
Lhe uveal tract of" erne eye may experience visual symptoms
caused bv either diffuse or multifocal areas of granulo­
matous choroiditis in lhe second eye,502-310 'Ihis is often
accompanied by evidence of iridocyclitis. Sympathetic uve­
itis occasionally occurs following unusual circumstances
such as proton beam, plaque, and helium ion irradiation
treatment of choroidal melanomas,'': and cycLodlode
Laser photocoagulaLion.''1-■I J I il3 't he posterior form
of sympathetic uveitis, in Which the curliest changes are
confined to the posterior uveal tract, probably occurs less
frequently1 than Lhe anterior or more diffuse form of the
d is e a s e .^ ^ " ^
The onset of symptoms in the sympathizing eye usually
occurs between 2 weeks and 6 months following injury lo
the inciting eye, though it has been reported even 3D years
from Ltie time of injury, lhe incidence is highest in the firsL
year after injury. Light sensitivity, transient obscurations
of vision, and lacrimation are frequent prodromal symp­
toms. I lie previously (raum.Ui^ed eye usually кЬо1 .^ ■
of inflammotion. E^tienLs with predomlriarldjr posterior-
segment disease may show evidence of either diffuse
(Rgure lli29A -C) or multifocal choroidal involvement
(E'igure 1LZ9D^G}. In the former there may be one or
more areas of localized serous detachtneni of the retina.
Ihese detach men Is soon become confluent and often
result in bullous retinal detachment, fluorescein angiog­
raphy may show evidence of multifocal areas of chorio-
capiliaris hypoperfusion and multiple pinpoint areas of
fluorescein staining that enlarge during lhe course of the
study (figure 11.24В, С, L, and
Salients with multifocal choroiditis may show scattered,
gray-while, stighlly elevated sub retina! nodules (ligure
11.29 D ) Lhat m ay extend t hrough out the fu ndus.' Ihe cl ini-
cat and angiographic picture of nmhilocal granulomas in
sympathetic uveitis simulates closely LhaL seen in APMPP1:
(E'igure '! ' 'lhe lesions in sympathetic
uveitis appear slightly elevated, where as in АРМ РРЁ they
are flat, lh e early-phase angiographic picture is identical in
both disorders, but in the later phases the central portion
of lesions stain5 less well in sympathetic uveitis [figure
11,29E and F), ]he posterior form resembles VKH disease
closely with pockels of subretinal fluid that show pinpoint
hyperfluorescence early, and leak dye into the SKL" Iale on
the angiogram (figure I I . 23 Ю ) . Some patients jnay
also develop hearing Loss, tinnitus, and vitiligo similar to
pa li ents w ith complete VKH sy nd rom e.! 9 '"1
11islopathologically, the uveal tract is infiEtrated by
eilher diffuse or multifocal areas of granuloma Lous inflam­
mation (figure 11.2UJ-I.J. lhe lymphocytic infiltration is
I ■,29 Posterior sympathetic uveitis.
A - С : ta r ly p o s te rio r ^ym patfietj® u ve ilis A n d m in im a l serous
retinal d e ta c h m e n t in Lhe rigjit e y e o f a 1 O -y e a r-o Ed b o y 2
m o n Lh s ч^Нег surgical re p a ir o f an a n te rio r sc.IctaI ru p tu re
□t Lhe left e y e C aused by a fiгесглскыг ini игу. H e n o te d Lbe
rece nt onsel Ol" b lu rre d v is io n in lh e righl e y e . V isu a l a c u ­
ity w a s 20/70 rigjit e y e a n d h a n d m o v e m e n ts o n ly left e y e .
1 here w e re 2 - LeIJs a n d flare in lh e a n te rio r ( h a n d le r o f
the raght e y e . h 'o le I Ke.- m u ltip le c o n flu e n t lig h t-g ra y I cfs-icjhe-
at the level o f lh e r h in a l pij^m finl e p ith e liu m :A i . These
le s io n *. W h ic h arc c a u s e d b y m u l:ifo c a l c h o ro id a l g r a n u lo ­
m a s , fjltslrucl lh tf c h o r io c a p illa ris a n d a p p e a r n o n fEu o ie s c e n l
ea rly. H ih Lo fM tlio lo g rc u s a m in a Litm o f lh e lefL e y e con-firm e d
Lhe d ia g n o s is o f s y m p a th e tic u v e itis .
D - K : 5ostaric+ s y m p a th e tic u ve itis s im u la lin g n cu le fjo s te rio r
m u lli focal p la c o id p ig m e n L ja iiilh e lid p a th y in a Н :-уваг-Ьр1
m a n w ith p h o lo p h o b ia , floaters, a n d pa racen tral S L O Io m a ta
in Lhe righL e y e b m o n th s a fte r p e flrtra tin g in ju ry Lo lh e lefl
e ye a n d 2 m u n lh s after л trans pars p la n a vi I ret I u rn v in lh e
sam e e y e . V isu a l a c u ity in lh e righl e y e w a s 2 № 1 5 a n d in
Lhe lefl е у н w a s n o Jighl p e rc e p liu n . Th e Ie*1 I e ye w a s ph Lh isi-
e a ]. N o l o ill'.! m u llip .!o ^ ra y -w h ite , s lig h tly e le v a te d , s u b re tf-
n a l I n s [h a t w e re also p re s e n t in Lhe p e rip h e ra l fu n d u s
I.D). th e r e w e r e a fe w in fla m m a to ry Le lls in lh e viln e o u s
a n d d t|U № U H h u m o r . T h e re w a s n o serous d e t^ Lh n iLT il u f lh e
re lin a . Early a n g io g r ^ m j bficjwed lEiat tiie subrelinril le tio n s
wi^re n o n flu tM e so e n l (E ). La te r a n ^ ia y ra m ii s h o w e d Iha I lh e
lessens stained in ilia I ly at lEteir e d g e s (F ). F o u r years laler
Lhe p a lie n L h a d e K p e rie n r:e d pTdgressive Loss o f peripEieral
a n d ce n lra f viu ien in spile e f curLic<)sleruid a n d с Ь З е т а т -
Ljucii Ire a lm e n t. N tiLe m u llip ie c;hurit)retinal scare a n d na r­
r o w in g o f the retinal v e s s e li ICJ a n d H . l -C]iqss e>£amina[]tsn
□I 1he p a tie n t's lel( e y e r w h ic h w a s e n u L le a te d 1 d a y a fle r
phciLugraphs in D - F r re v e a le d m u ILi p ie g ra y -w h ite lesions
(arrow s) in th e c h o r o id df- T h e retina w a s totaTLy d e la c h e d .
H is to p a th o lo g ic e x a m in a tio n re v e a le d m u ltip le c h o ro id a l
^ ra n u km ^a s anti U a le n -]-u c + is n o d u le s liarrows-, } a n d K .i c o r-
re s p o n d irijg w ilh t!ie gray lesions n o le d In J , H iy h - p o w e r v ie w
o f e h o ro id a l g ra n u lo m a s a n d Lla le n -h u c lis n o d u le s ia rro w s ,
K.i re v a a le d o b lite ra tio n o f lh e e h o rio c a p illa iis h e n n a th the
n u d u le s .
созпposed of predominantly L'-activated lymphocytes, lhe
L'-helper to suppressor ratio is approximately 3:1:4:1. :
The underlyEtig immune pathogenesis Ln sympathetic uve­
itis is probably a delayed hypersensitivity to ocular anti­
gens, melanin or related anltgen, and/or a soluble fraction
from the outer segments of the receptor cells similar lo
lhat found in VKH syndrome/^
Jit the diffuse form of sympathetic uveitis the inflam­
matory reaction may spare the choriocap ilia ris. bul in
lhe nodular form of the disease it causes occlusion of the
choriocapillaris and Inflammatory cellular detachments
of the RE3E: [Ualen-f'ucbs nodules) (Mgure 11.2^Ev and
ц |heH, Iatt£f nodu]?s forrespond
wilh the mulllfocal gray lesions that show delayed central
staining with fluorescein
©
 Kao and his group experimentally induced a granulo­
matous disease that closely jviiniics sympathetic ophthal­
mia by using 5-10 |ig of retinal S antigen. In Lheir study
of experimental allergic uveitis in guinea p^gs, they found
Varying the dose of S antigen induced varying severity of
uveitis; ,50|ig produced a m otive panophthalmitis con­
taining polymorphonuclear leukocytes, eosinophilic and
mononuclear cellsv 25pg. produced д less severe panuve­
itis, 5-]0|ig produced а granulomatous uveitis made up
of epithelioid and mononuclear cellsr and 1pg produced
nongranulomatous uvellis. Lowering the dose eliminated
polymorphonuclear leukocytes and eoslnophllsr sug­
gesting higher antigen dosages may either superimpose
Immune complex response or replace a celt-mediated
Immune disease.'
llolh the diffuse and the multifocal choroidal lesions
of sympathetic ophthalmia Will respond promptly Lo sys­
temic corticosteroid therapy, and they often leave mulliple
focal ,srea& of liP E atrophy and depigmenLation of the cho­
roidal melanocytes (I'igure 11.291] and I). Txacerbalion..
however, is соmnton. Immunosuppressives such as anti-
metabollles - methotrexate and cytoxan - and immuno-
modulating drugs such as mycophenolate mofetil are
necessary in severe and recurrent cases. High-dose initial
treatment followed by a low-dose maintenance therapy
is necessary. Placement of an intravitreal steroid Implant
may be used for selected cases where the inciting eye may
he enucleated or phthisical. SubletLnaI neovasculariza­
tion may occasionally arise In one of the macular scars.
Severe chronic inflammation may cause marked prolifera­
tion of subretinal fibrous tissue, widespread degenerative
changes in the № E, narrowing of the retinal vessel, night
blindness, and eventually total blindness.333 Ihe value of
enucleating the inciting eve after sympathetic ophthalmia
has set in is open to q ^ o i L 3^ * ^ 31^ 56
И .29 Continued
L —O : This -fa -v tJflr -o H n_„ik> im m In d ia d e v e lo p e d e x u d a -
t i w re G n a l d eln t h m t'n l in liiu 1еЙ u ye (L:■a tow V e a ^ ;iflc?r the
ri^hl e y e h a d a b e fje tra lin g in ju ry. H i^ v is itm y ^ s 2 0 /4 0 0 in
his (in ly e ye lh a l s h o w e d e a rly h y p o flu o re s c e n t sputs in Lhe
te m p o ra l m a c u la w ith лррелгапиу o f tin y p in p o in t dots
Iа к т in Lhe a n fjid g ra m IЬлI e w e n lijally le a ked flu o re b ce tti Ih^iI
p o l l e d in lh e subretia.al iN am J C l .
lL - O r i r Ju r ttiy lit Гч V ibh.U j L.■u |□Г,i .
An increased frequency of Ш-А-А11 antigens In patients
wilh s\rmp4tlhelic uveitis suggests that a genetic factor т з у
phrv a role in its pathogenesis.11'
Sympathetic ophthalmia may rarely occur in the setting
of bacterial endophthalmitis or other infections. uo In
patients with exogenous postoperative bacterial endoph-
ihalmitis or endophthalmllis following traumar signs of
inflammation in the fellow eye should alert lhe ophthal­
mologist about lhe possibility of sympathetic ophthal­
mia. In a series by Rathinam and Дао, of 26 patients with
sympathetic ophthalmia, 4 also had bacterial endophthal-
mitiSr most of them postoperative.340 It was believed pre­
viously that an Infection would destroy the antigens that
induce sympathetic ophthalmia; however, the infection
may not he as severe and some antigens may persist that
can incite sympathetic response. It is also possible for
patients with sympathetic ophthalmia to present only wilh
posterlor-segmenl findings when termed posterior sympa­
thetic opbLhalmia.1-11 'Jhese patienls may show evidence of
anterior-segment involvement or vitritis only at the lime
of recurrence and not at the first episode of sympathetic
ophthalmia. Any signs of uveitis, especially associated with
exudative retinal detachmenl in a fellow eye, should alert
the ophthalmologist about the likelihood of posterior
sympathetic ophthalmia.1''
ACUTE EXUDATIVE M.3fi Acute exudative polymorphous viteEliform
maculopathy,
POLYMORPHOUS VITELLIFORM
Л —C : In |u n e "lEJfJ2 this 2 4 - y e a гнэ1 cl m a n preambled w ilh a
MACULOPATHY 2 -d a y history Ы Head&chieil a n d p ro g re ss ive loss o f v is io n in
b o th e y e s. H is vis u a l a c u ily w a s 2 tV 5 0 f rig h t e ye a n d 20/40,
t^ass and to workers reported iwo young lightly pig­ loft e y e . 1 1тсче w a s e x u d a tiv e d e ta c h m e n L o f the reLjna c e n ­
mented white adult males who presented because of (tie tra II v. ;tn d n u m e ro u s o v a l. ro u n d , a n d c u tV illn e a r y e llo w -
acute unset of headaches and visual loss associated with w h iLe lesions u n d e rly in g coni'l иел I M is le d ik e areas o f serous
multiple yzllow-wBite til-defined subretinal lesions and relinal nttaLilSrrierirt b ila te ra lly >A artd & ). N o L e the striking
serous rellnal detachment in the macular area of both e a rly h y p u rllu o rre c e n c u ol the y e lk jw - w h ile lesions ( t ) a n d
m in im a ! late s ta in in g ( D ) . H e re c e ive d p re d n is o n e BO m g
eyes (I'igure П.30А, B, and I I } . 1'4'1'Ihe focal lesions dem­
daiEy a n d 1 w e e k later visual a c u ity w a s 20 /20 , n g h L e y e .
onstrated early hyperfluorescence and mild Lite staining
a n d 2 0 / 2 5 , lelL e y e . A c c o m p a n y in g re s o lu tio n ot lh e sutjreL-
(I'igure ! 1.30C, D, and I]. One patient. had a few vitreous irial flu id w a s lhe1 d e v e lo p m e n t o f lar^ye a m o u n ts o f y e llo w
cells. Both patients were treated with oral corticosteroids. subnet in ,нI m a le ria l lh a l snow ied a te n d e n c y Lo gr-iLvilate in fe ­
Over the following weeks gradual improvement of visual riorly it. D e c e m b e r 1 9 3 2 , a n d F, Ju n e 1 9 Б З ). W h e n Iasi seen
acuity was associated wilh development of prominent in |Lino 1 Э Й 4 . visual a c u ity w a s 20 /20 ^ R it E r a il y *m d m osL o f
polymorphous deposits tif sublet iл nil yellow pigmenl lhal LEie y e llo w m a le ria l h a d d is a p p e a re d ( G ) .
H - L : This- 3 0 -y e a r-o ld p re s e n te d w iLh a 1 -m o n lh history o f
tended lо gravitate lo form a meniscus, giving an appear­
vis u a l loss a n d severe h e a d a c h e s . H i s fin d in g s a n d c lin ic a l
ance similar it) lhal in Best's viletliform dystrophy [figure
co u rse w e re s im ila r lo th o se d f Lhe? p r e v io u s p a lie n L. H a n d I.
11.3OH. l\ J, and K). '['he visual acuily relumed to normal A u g u s l 1 1) &4r I a n d K . A p r il I Э Й З ; L.. O c l o t ie r 1 9 8 5 .
levels and incomplete resolution of the yellow pigmenl
lA-L fr o m ( .J j s v в .1 1. '" '" I
occurred in both patients. Et is probable lhal lhe yellow
pigment is a product of dnVinaged pigment epithelium
and/or photoreceptors and not a result of lipoproteins
escaping From the choroidal vasculature. Both patients bad
subnormal eleclro-oculographic findings, but neither had
a family history of eye disease, '['he peculiar fundoscopic
and angiographic findings during the early stage of this
disease are similar to those which occur in patients who
present Tvilh bilateral acute visual Joss and retinal detach­
ment caused by bilateral uveal melanocytic proliferation
associated wilh an occult carcinoma [see p. 1202).
 Since the origin лt description of two men by Cass in
IVflS. there halve been several isolated reports оГ acute exu­
dative polymorphous vitelliform maculopathy thaL have
been described, including women, and even in л child al
age i i T h e majority of patients show a decrease in
LOG function, which may recover. Multifocal l-Жг has
shown decreased cone function in the acute phase, some­
times persisting even after visual recover}- has occurred.''11
]he yellow material hangs around in lhe sub retinal space
for several months, even up to 1 or 2 years. A few patients
show complete re&oiuLioii of lhe yellow material with no
residual macular changes; however, many of them show
focal irregular pigment epithelial atrophy and changes.
On ijCGr the material Shows gradual hyperfluorescence
and staining similar Lo the appearance on fluorescein
angiography (Rgure ll.3 lO ).u 'Ihere is increased auto­
fluorescence of Lhe yellow material, ' 11 suggesting these
fluorophores are byproducts possibly of photoreceptors
(E'igure I] .31Г and Q ] i leadache is a persistent find­
ing in most of these patients. There has been a variable
response to steroids and generally the yellow material and
the serous detachment resolve over several months Lo 1-2
wars. О С Г shows (hat the yellow material lies between the
ftPE and the photoreceptors and is also characterized by
several isolaled or confluent serous detachments.
M .3 I A c u t e id r o p a L h ic e x u d a t i v e p o l y m o r p h o u s
v ite tlifo r m m a c u lo p a th y ,
A - 1 : O n lune 3 0 , 1 4 3 2 r this p re v io u s ly h e a llh y 2 4 -y e a r-o ld
iTi-iLn p re s e n te d w ilh л 2 -d a y h isto ry n l a cu Le h e a d a c h e s a n d
foss o f v is io n in b o th e y e s. V is u a l a c u ity , rig h l s y e w a s 2 0 /5 0
a n d left e ye 2 0 / 4 0 . In b o lh eyes ib e re w as an oval serous
relinal d e la c h m e n l s u rro u n d e d by ra d ia tin g теИпаГ to Ids in
lh e ce n tra l m a c u la , a n d n u m e ro u s o v a l , ro u n d , a nti irre g u la r
y e llo w -w h ite lesions u n d e d y in g c o n flu e n t b lis te rlik e areas
of serous retinal d e la c h m e n l I hat e x te n d e d th ro u g h o u t the
m a c и I я г a n d ju \ la p a p ilE a ry areas - A a n d li'i. E a rly -p h a s e a n g i­
o g ra p h y re p e a le d m a rk e d h y p ^ S u u r e s c e n c ^ c o rre s p o n d in g
w ith th e y e llo w - w h ite lesion s ( C j. L a lw a n g io g ra m s s h o w e d
slain in g o f Ibese lesion s, Еэи1 m in im a l e xte n s io n o f Lhe tiye
in lo Llie s u b re lin a l fluid ( D ) . H e re c e ive d oral p re d n is o n e a n d
e x p e rie n c e d a ra p id return o f vis u a l a c u ity Jo n e a r n o r m a l.
O v e r the s u b s e q u e n t 8 -m onths, h o w e v e r, b e d e v e lo p e d a n
u n u su a l p o ly m o r p h o u s p a H e rn o f v ile llifo rm e x u d a l j w s u b -
nelinal d eposits IE a n d F, O c t o b e r 1 9 B 2 - О a n d H , D e c e m b e r
1 9 3 2 J . T h e s e d e p o s ib c le a re d s lo w ly b ul w e re sLiJI e v id e n t 2
years later in b o th eyes (I).
| - L : This 2 4 -y e a r -o ld m a n d e v e lo p e d h e a d a c h e s a n d bilateral
visual Ions 2 w e e k s after a m o to r V e h ic le a c c id e n t. H is vis u a l
a c u ity w a s 2 0 /5 0 r rig h t eye? a n d 2C V30r left e y e . B o lh e ye s
s h o w e d ^ n o p h th a lm o s c o p ic a n d a n g io g ra p h ic p ic tu re irlen-
lical I d that in A - D . O v e r lh e fo llo w in g 2 w e e k s the- p a tie n t
s p o n ta n e o u s ly b e c a m e a s y m p io m a Lrc . H e refused fu rth er
e l i m i n a t i o n u n til 1 y e a r 3ater w h e n h e re tu rn e d w ith 20-,2 0
vis u a l a c u ity a n d m u ILi p ie v ile llifo r m lesion s s c atte re d in the
p e rip h e ra l m a c u la r areas.
 A similar Appearance has been seen as a paraneoplas­
tic manifestation in patients with metastatic cutaneous
and choroidal melanoma. Some of these cases have been
unilateral.4 ,J,bl) Lksandh et al. reported positive anti-
bestnophln antibodies in a patient wilh a solitary macular
vltelllform lesion with ,1 history of metastatic choroidal
melanoma (лее Chapter i 3). ' ' 1 It is ttol known whether
acute exudative polymorphous vi tel li form maculopathy is
an acquired inflammatory disease or an unusual manifes­
tation of a genetically determined disorder, such as Best's
disease or some other as-yet poorly defined RPE dystrophy.
M.31 Continued
M - R : A 3 fi-y e a r-o ld h e a lth y m a le p h y s ic ia n p re s e n te d w i lh
p it U a c h e s Ih. 1 L w o rs e n e d lo w a rd s the e л d o f lh e пай Io j 2 - 3
m o n th s . H is vis io n c o u ld h e cor reeled w ith л n i l cl h y p e r­
o p ia a s li^ m H lic c o rn e d io n Lo 2 C S G O - in eat h e y e . T i m e w e re
several sm all v ite Elifo rm lesions in th e p o s te rio r p o le a n d a
larger p o c k e t o f su b retin a l flu id w it h ye Elu w m a te ria l at its
b o tto m in Ejoth f b ^ a s ( M a ^ d N i . In ^ o c y л n in e a n g io g ra p h y
s h o w e d late Eiyp e rflu o re sc e n c e d lh e y e llo w lesions in Ejolh
eyes ( u ) ; T h e v ile llifo r m m a te ria l w a s tw illia n lly a u Eo flu D re s -
cenl in b o th eyes f S a n d CJ.i. H Ijic? 4iгтлI flu id pockcfl c o u Jd b e
seen o n o p tic a l c o h e re n c e lo m o ^ r a p h y im a g in g in b o th e ye s
iK>. H e w n s kep i U n rfe f o b se rve Li ол (fiitfaFEy. N o ;h a n ^ e in
Lhe lesions after 4 w e e k .1; p r o m p le d a c o u rse o f system ic ste­
roids lo r a c o u p ie o f m o n th s . H e d id n o l je L u m io r to Ilo w -u p
bul w h e n c o n ta c te d by p h o n e re v e a le d s la b iii2 a t(d q o f v i v o n
a n d resole I i o n o f h e a d a c h e .
PROGRESSIVE SUBRETINAL
FIBROMATOSIS
Ophthalmoscopic evidence of varying amounts of while
fibrous metaplasia of lhe RPE occurs in a wide variety of
diseases causing relinal detachment.. including idiopathic
central serous chorioretinopathy, senile macular degenera­
tion large choroidal nevi (see figure 14.01 melanomas.,
serpiginous choroiditis (i'igure 11.13D-H}, sarcoidosis
(see i'igure I1;3G| and I.}, and P O U S .^ v'2 In some cases,
particularly patienls with MC£ ihis reactive metaplastic
reaction may be massive and mask lhe underlying cause
(E'igure l ll f li U C j . : ^ 352 ! ' Cass has seen two such
patients, who, without a recognizable cause developed
m ullifocal choroiditis and severe loss of vision associated
wilh progressive growth of a thick plaque of white sub reti­
nal fibrous tissue, presumably metaplastic ftiPE frtim (he
juxtapapillary areas, throughout the macula and into the
peripheral fundus (I'igure II. 321)-]). The profound visual
loss in both cases was tiol fully explained on the basis of
the fundus findings. Elistopalhologic examination in one
eye of each of two elderly palients who became blind in
both eyes within several years of the onset of the disor­
der (i'igure H.32G-]) revealed widespread destruction of
the retinal receptors and pigment epithelium and mas­
sive subretinal proliferation of fibrous lissue (presumably
metaplasia of lhe RPli) overiying a dEffuse lympbocylEc,
plasmacylic, and granulomatous choroiditis (hat was
centered around fragmented, degenerated, and calcEfied
Ип±сЬ\ membrane.-’'"1"^'1'
К Em et al. reported simElar histopalhologEc find Engs of
.1 '.v. n'.pidiv :vi',iim' :4-nd Iu 'i '.msl'
of progressive suh re tin a! fib ru m a lo s is .'I hey described
electrott microscopic evidence that (he subretinal fibrous
tissue was derived front metaplastic pigment epithelium,
ihey also found that the relinal Muller cells expressed
class ]J an Ligens of the maior histocompatibility complex,
i'hese authors and Palestine et al.3'' theorize that Lhe hEs-
topathologic changes may be caused by an autoimmune
1 1 .3 2 M a s s iv e s u b r e t i n a l f i b r o m a t o s i s .
A - С : A h e a llh y b la t k Vfcoman n o te d p r o g r e s s iv e le s s
yqU ng
01 v is io n in h u th N o L e the th ic k
eves. o l w h ile fib r o id
Lin к и е s u r r o u n d i n g lh e o p l i c d is c a n d e x te n d in g I h r o u g h o u l
m ost d F th e p o s t e r i o r fu n d u s . M e d ic s I e v a l ид Iran faiEed Id
re ve a l a c a u s e l or Lh is. p ro c e ss *.
D —| r A haallEiy 6 & -y e a T -o ld w h ite w o m a n d e v e lo p e d ijra n u -
lo m a lo u H u ve itis Ln Eiolh eyes a n d e x p e rie n c e d progressive
loss ol v is io n in Lhe lefl e y e to n o light p e r c e p tio n , a n d in
the righl e y e (o light p e rc e p tio n o n ly , w ith in 3 years. Th e left
fu n d u s w a s o b s c u re d b y a c a t a r a c t There w e re w id e s p re a d
areas o f p e rip h e ra l a n d p e rip a p illa ry s u b re tin a l fib ro u s tis­
sue p ro life ra tio n in the rig h t fu n d u s (1 3 -F ). T h e o p lic d is c w a s
p a le . \e u n o lo f^ iс a n d m u d ic a ] e x a m in a tio n w a s n e ^ a liv e .
T h e left e y e w a s e n u c le a te d . H ts to p a tE io la g jc e x a m in a tio n
r e v e a l e d e x te n s iv e s u b re tin a l fib ro u s m e t a p l a s i a o f the relinal
p ig m e n t e p ith e l'Lim (a rro w s , С a n d H ) o v e rly in g , a g r a n u lo ­
m a t o u s re a c tio n c e n te re d a ro u n d a fra g m e n te d a n d d e g e n e r­
ated B ru c h 's m e m b r a n e lh ro u ^ h o L il the u y e i > l - | .. N o l e gianl
cells, s o m e o f w h ic h are e n g u Flin g p ie ce s o f c a lc ifie d B r u c h s
momEtrane larrow, II.
lA - ( . i 11111 r-*■' Ы M i. W i l l . . L i n K . k im m .i
anlibody-medialed inflammalion in which local antEbodv
production lo the RPli occurs, ihe clinEcal and hislopalh-
ologjcal findings in the iwo patients descrEbed previously
suggest Lbat the immune read Eon may have been dErected
lo tbe photoreceptors as well. The granulomatous compo­
nent of the inflammatory reaction may he a lale response
lo the Emm Line reaction-damaged and devitalised iimch's
membrane, similar to that seen around Jlruch's membrane
in eyes of primates with experimentally induced autoim­
mune uveitis to inLerpholoreceplor retinoid-binding pio-
lein,J ''' inflammalion surrounding iiruch's membrane and
the inlernat limiting membrane of the retina afler herpes
zoster chorioretinitis/’’'1 around degenerated tfescemet's
membrane after herpes simplex keratitis/'" and in the
vicinity of calcifsed and degenerated inLernal elastic lamina
of large arteries in giant cell arteritis.
Pjtfgfcssilre SHimrfm0j| J j'^R’rrjrrfnsi's 101 5
POSTERIOR SCLERITIS
Rheum ate id scleriLis is an inflammatory disease that may
involve the sclera, eiLber diffusely or in a circumscribed
fashion. rl'he intensity of the inflammatory reaction var­
ies from that of ait acute necrotizing granuloma nil one
end of the spectrum to л very low-grade chronic scleros­
ing granulomatous inflammatory reaction.''"" Although
most patients have involvement of the sclera anteriorly, in
approximately 10-15% of cases the focus of scleritis and
overlying uveitis may lie confined to the posterior portions
of the globe and produce a retinal detachment vviLh or
without a sub retinal tumefaction f figures 11..13, 11..^418-1
and И .ЗЗ ).’11'0' 1,1In the latter patients, ocular pain or ten­
derness. injection of the conjunctival and episcleral ves­
sels, evidence of intraocular inflammation, and a history
of rheumatoid arthritis [present in only 50% or fewer of
the patients) are features that should arouse suspicion
of sderitis. Acute posterior sclerilis may cause multifo­
cal areas of white sub retinal exudation and serous retinal
detachment {Jigure 11.33A, L, and (Jj. In some patients
an acute inflammatory reaction surrounding the focus
of necrotic sclera is sufficiently violent that a posterior
scleral abscess occurs and produces a sub retinal hypopyon
(t-'igure 11.33G) or a rapidly expanding subretinal mass,
retinal whitening, and exudative relinal detachment and
vitriLis { l:igure 11.33К and L).i6i: 'Ibis is accompanied by
severe pain and in some cases proptosis.
11.33 Posteri or scl eri tis.
A - О : U n ila te r a l p o s te rio r sclerilis in a 2 4 -y e a r -o ld w o m a n
c o m p la in in u o f p a in a n d loss o f v is io n m lh e lefl e y e . N o t e
the ill-d e fin e d w h ite a reas l-arrowsi iH jn e a th lh e l o c a t e d
senjus retinal d e la c h m e n l in lh e m a c u la ! A I. A n g io g ra m s
(stereoa n g iojjra m s Ы—D ) s h o w m u ltilo c a l leaks at the level o f
lh e retinal p ig m e n t e p ilh e liu m ( K F t l in lh e area o f c h o fO id o -
Kcleral Сh icken i ng.
E a n d F : This A 1 -y e a r-o ld b la c k w o m a n n o te d b lu rre d vis io n
a n d p a in in [fie right e y e . S h e h a d in je c lio n o f the rfghl e ye
a n d m ild p ro p to s is . T h e re w a s ju x ta p a p illa ry serous retinal
d e la c h m e n l -and the w h itis h subrel i r: a I e x u d a te I t -.
G —I : This w o m a n n o te d a c u te onsel o f p a in , re d n e s s , a n d
a s u p e rio r s c o Lo m a in the left e y e . 5he h a d e p is c le ritis , a n d
p o s te rio r sclerilis a sso ciate d w ith a lo c a liz e d e x u d a tiv e
d e la c h m e n l o f the retina i a n o w h e a d s , G l inferm rSy. N o 1 e th e
im e n se w b ile n in g a n d fle c k ь o f H ubretm ai b k to d а I lh e fo c u s
o f s c le ro c h o ro id itts fw h ile a n o w ) a n d lh e s u b re tin a l h y p o ­
p y o n Ib la c k a r r o w i. A n g io g ra p h y s h o w e d s e in in g in itia lly
in lh e area o f R РЫ d a m a g e a n d later staining o f the su b ieLi-
n.al e x u d a te ( H ) . U ltra s o u n d Ц ) re v e a le d foca l th ic k e n in g o f
lh e c h o To id o s c le ra l layer a n d a n e c h o lu c e n l i o n e o v e rly in g
Ihis area p o s lw io r ly . H e r s y m p to m s a n d o c u la r c h a n g e s
re s p o n d e d p r o m p t ly bo system ic c o rtic o s te ro id tre a tm e n t
f—L : A n a c u te p o s L w io r rh e u m a to id 5сГега1 abscess d e v e l­
o p e d in lh e lefl fu n d u s o f a 1 9 -y e a r -o ld w o m a n w ilh se vere
in tra c ta b le p a in a n d vrsual toss in Lhe left e y e (K ). N o t e
lh e w h ile s u b re tin a i e x u d a le o v e r ly in g a n elevak>d s c le ro -
c lio m id a f m ass. S h e h a d a p a s l h islo rv o f a c u le n e c r o tiz ­
in g s c le filii; in lh e lefl e y e (Jl, ih r tjm b o c y lo p e n ic p u r p u r a ,
pcilyarlhrilis, a n d p n e u m o n ia . Th e ocuSar p a in a n d abscess
fa i ted to re s p o n d lo s ys te m ic c o itic o s le ro id a n d a za th io p r in e
th e ra p y . S u r r e a l d ra in a g e o f lh e scl-eral abscess resull-ecf in
p r o m p l re s o lu tio n o f lh e e x u d a ttv E m a s s , retinal d e la c h m e n l,
a n d p a in ( L ) . Several vears later 1 h iн p a lic n l d ie d b ecau se o f
w id e s p re a d u n c la s s ifie d c o lla g e n va s c u la r d isease.
/101 sijijjpS
 In other patients the inflammatory reaction is subacute
and fewer т А д ш ш Ь г )' signs accompany the develop­
ment of a sub retin,si mass and retinaE detachment. ]n still
other patients there may be no clinical history or find­
ings to suggest the presence ol" an underlying chronic
granulomatous mass lesion that is largely confined Lo the
sclera [E'igure П.ЗЗА-Е'}.1"1' r"7 In patients wilh jninimal
signs of inflammation elevation of the relatively intact
choroid and RPE produces an intraocular in ass that is
orange-colored. 'J"he presence of focal lymphoid follicles
in Lhe choroid may cause scattered yellow-white nodules
on the surface of the tumor [I igure IE. 35A, E3. and D-C).
Chorioretinal folds are frequently evident ophlhalmoscop-
ically and angiographicalEy at the edge of Lhese tumors
[I'igure 11-35C). v,i I'ocal areas ofsderitis, when located
anywhere in Lhe fundus, may be associated with cysloid
macular edema (]:igure 11.35JJ. Chronic scleritis jnay
occasionally be the underlying cause of uveal effusion. '"J
Branch retinal artery occlusion and simultaneous central
retina] arteiy and w in occlusions have been described in
severe c a s e s .1-3,"L
fluorescein angiography in patients with acute and sub­
acute posterior scleritis and localized exudative detach­
ment typically shows multiple small foci of leaking al the
Eevel of the RPE {Figures 11.33B, С, D, and l\ and 11.35Л
and [). In chronic scleritis angiography often demonstrates
evidence of folding of the inner choroid (figure 11.35C).
Angiography es of little value in differentiating either the
acute or the chronic nodular scleritis from melanomas,
lhe characteristic histopathologic lesion in rheumatoid
scleritis is a zonal type of granulomatous inflammatory
reaction of variable intensity around a focus of necrotic
sclera.
The acule and subacute lesions usually respond to
systemic or intraorbital injections of corticosteroids.
Konsleroidal anti-inflammatory agents used alone or com­
bined with corticosteroids, as well as intravenous pulse
corticosteroid therapy.- may have some advantages over
orally administered corticosteroids alone.' "" !l lhe large
brawny lesions containing much fibrous tissue respond
poorly to corticosteroid therapy [E'igure 1L.35A-JF);
CycEosporine and mycophenolate mofetil therapy may be
helpful in severe scleritis refractory to other treatment.
Ultrasonography is useful in differentiating these
lesions from uveal melanomas (figure II.33E). Scleral
thickening, producing moderately high internal reflectiv­
ity, with an adjacent echolucent area caused by edema in
'Jenon's space is characteristic of posterior scleritis (E-igure
11.341).Л|:: Computed tomography Enay also be useful in
И .34 Posterior scleritis —systemic associations,
A —E h 1 Ьгн 7 3 -y e a r-o ld w h ile m a le b a d re c u rre n t a lt s o d e s
at sclerfLis. Т Е » first e p is o d e o c c u r re d S m onths- p re v io u s ly
a n d w b s trea ted w ilh o ra l p r e d n is o n e . H is m e d ic a l h is to ry
was s ig n ific a n t fo r ty p e 2 diaEjeEos. b v p e rlip id e m ia , a n d
m ild a rth ra lg ia . V M i a l a c u ity w a s 2 0 /3 0 in the rigbL eye? a n ti
2Q /6 H in Lhe left e y e . In Lra o cu la r pressure w a s l i m i n H j j o n
the right a n d 2 6 m m H g o n the left. H i e lefl lu n d u s s h o w e d
2 + v ilre o u s cells a n d m ftd n o n p ro life ra tiv e d ia b e tic re-Li -
n o p a l hy. The rigbl e y e a ls o h a d p o r p r p li ie r iljv e d iabeLic
re lin o p a Lh y . T h e left e y e re v e a le d d iffu se scleriLis a n d Eie w a s
slarted o n a b ig b d o s e o f o ra ! steroid s, to p ic a l Coscspt, a n d
LopicaE s te ro id s. O n e m o n th later b e d e v e lo p e d n ig h t sw eats
a n d a lo w -jjrn d e fe v e r w ith in le rm ille n l th r o b b in g d is c o m fo rt
in his ri^hE a n k le jo in t. H i * vis u a l a c u ity w a s 20/25 o n the
rigjit a n d 2Q /BO in the le ft. T h e left fu n d u s s h o w e d c y s to id
m a c u la r e d e m a LhaL w a s v is ib le o n Lbe a n g io g ra m IE3 a n d Q ,
H e c o m p la in ts ! o f e a r p a in o v e r th e last year. A t his (h ird e p i­
s o d e , re c u rre n t le ft-e a r p a in a n d s w e llin g lL>:- h e lp e d m a k e
Lhe d ia g n o s is o f re la p s in g p o Jv c h o n d ritis .
f-C A 7 2 -y e a r -o ld w o m a n w iLh rh e u m a to id arlhrjEis a n ti
history o f re c u rre n t sclerilis. iihe w a s slable w ith 2 Q / J O v is io n
till sEnf c n m e o ff steroids a b o u l 1 0 d a y s Em fore. ^Eie re tu rn e d
w ith s evere pa?nr re d b e s j (E )f a n d Iofs o f v is io n . D iffu s e
sclerilis w ith e s le n s tve e n u d a liv e d e la c h m e n t (F a n d C ^.
U b r a s o u n d If sen и s h o w s c h o ro id a l Lhiickeninj’ n n d flu id in
Lhe s u b -T e n o n spa-се d e m o n s tra tin g Lhe 7 sign, i h e re c e ive d
in lra v e n o u s S d jju -M e d m j nnd w a s restarted o n p re d n is o n e
a n d [Tics serous rclin a l d e la c h m e n l re s o lve d .
H - J : This I У -y e a r-o ld w o m a n b a d a hisLoi v o f re cu rren l
d e e p , b o rin g p a in in her lefl e y e for 2 — years p re v io u s ly . The
p a in o fte n w o k e h e r up t'rom s le e p , i h e h a d b e e n d ia g n o s e d
as p la te a u iris for this a n d re c e iv e d g o n io p la s ty (J) p re v io u s ly .
N o L e Lbe p e rip h e ra l iris spots fro m lb e g o n io m iS ity ■!.. Th e
p a in a n d in fla m m a tio n fro m the scleritis m a d e b e r u n a b le lo
ope?n h e r e yu !H .-. l-u n d u s e x a m in a tio n shtju-ed retinal fold s
in the m a c u la . A n u ltra s o u n d В scan ft) s h o w e d s u b -T e n o n
flu id c o n firm in g p o s te rio r scleritis, vvhicb re s p o n d e d 1o oral
steroids w iLh re s o lu tio n o f h e r s y m p to m s .
I A lo Ц L o u r k is y o f U r H iu ijp u t D h . i l i w i L A - l . A kr> V in h liU E Ii Luwr(;n<.4.- 1 ,
Ih e ftctinaL A tip ij S ju n d S f£ 10 10, *f7R-U-7tf20,3.J 10-9, p .l 'H :.
the differential diagnosis of posterior scleritis.^1- lhe phy­
sician must be aware, however, of the occasional asso­
ciation of placoid choroidal melanomas and posterior
s c le r it is .'L'bese patients m^sy present with ocular pain,
blurred vision, and anterior-chamber and vitreous inflam­
matory cell reaction that respond to corticosteroid therapy1.
Occasionally eyes have been enuclealed wilh a mistaken
diagnosis of choroidal melanoma. Severe pain and lack
of anterior scleritis led to a mistaken diagnosis of plateau
iris and gonioplaslv in the patient shown in E'igure 11.34
 Gass has seen posterior scleritis jn 2 patients with typi­
cal psoriatic arthritis (Rgure U.35G-L] in te rio r scteri-
tis has also been reported in association with Wegener's
gra nuio mitosis,v'2" 7 re] aps mg polyc hon dri tis.3 3S!>
procain acnide-induced lupus,'"" systemic idiopathic hbro-
sivM| toKopEasruosib retinochoroiditis^92 and malignant
melanoma of lhe choroid.!et Wegener's granulomatosis is
a necrotizing granulomatous vasculitis lhal causes sinus­
itis, necrotizing lung granulomas- glomerular nephritis,
and involvement of olher organs, including the eye. In
[he lalter case, it may cause proplosis, orbital cellulitis,
sclt'ritib.. keratitis, marginal corneal scleral ulceration, and
optic neive vasculitis. A few patients may present early in
the course of the disease wilh loss o f central vision as a
result of a combined uyeal and retinal detachment caused
by an area of sclerouveitis.'182"^ ' ]ensen el al. reported an
unusual association of an epihu Ibar granuloma and a mas­
sive nodular scleritis in a 5-year-old boy with no evidence
of systemic disease/"'1' lie lapsing inflammation of the car­
tilage of the other ear with nonerosive polyarthritis and
chondritis of the nasal cartilage, tracheobronchial chon­
dritis, and lesions in the inner ear is a feature of relapsing
polychondritis, '['he ocular findings have been reported
wilh proplosis, lid edema, lacrimal pseudotumor, epi­
scleritis, scleritis (figure П.34А-Ю), choroidal infiltrates,
uveitis, and op Liс neuritis. High-dose steroid therapy along
with cyclophosphamide, and dapsone have been used.
Plasmapheresis can be used for severe relapses.
Most patients with posterior scleritis are adults and there
is a slight preponderance of females. Wald et Щ reported 4
boys with diminished visual acuity, mild ocular pain, Lack of
systemic disease, exudative retinal detachment, mulliple pin­
point leaks angiographically, and b-scan ultrasonographic
evidence of sclera! and choroidal thickening lhe latter
was accompanied by evidence of episcleral edema in only 2
patients. Ihey all recovered good visual function after treat­
ment with corticosteroids and noneorticosteroid medications.
Wald el al. attributed this syndrome to posterior scleritis but
could not exclude the possibility of Harada's disease.
Occult posterior scleritts has been implicated in the
causation of idiopathic chorioretinal folds [see Chapter
4).'л ' "ы Whereas chorioretinal folds are a frequent mani­
festation of acute and chronic posterior nodular scleritis,
il is not known whelher inflammation of the sclera is a
precursor of the shrinkage and flattening of (he posterior
sclera that are characteristically evident ultrasonographi-
cally in patienls with idiopathic chorioretinal folds.
Surgically Induced Necrotizing Scleritis
SINS is a progressive scleral melt associated with inflam­
malion occurring al previously operated scleral sites, most
often after plerygum surgery with mitomycin and less
often after strabismus surgery oral sclerotomy sites (figure
11.35]-1.). Judicious use of local and systemic steroids with
immunosuppressives such as tacrolimus юзу be necessary
to treat the condition.
И .35 P o s t e r i o r s c le r it is .
Д - R H y p e r lr o p h ic p o s te rio r g ra n u lo m a lo u s sclc-ntis s im u ­
la tin g m a lig n a n t m e la n o m a o f (b e c h o r o id in a h e a llh y
3 4 -y e a r-n ld -C uba n w o m a ri m t tip la in in ff o f due ген bed v is io n
u n a s so c ia te d w ith p a in in Ih e ri^hl E y e o f u n c e rta in J u r a -
Lit] л . H e r a c u fW in m e fig h t e y e w as Lind in Lhe lefl
e ye w a s 2(У2£}. S h e w a s w e a r in g a h y p e r o p ic c o rre c tio n o f
4 .5 D in [he ri^hl e y e a n d 1 . 5 L> in Lhe lefL e y e . There w a s a
Earge, n o m jig m e n Le d , b te n g e subreLEnal mas?- ( A a n d H'i in Lhe
s u p e rio r te m p o ra l q u a d ra n l. The e x te n d e d p o s te rio rly
in to lh e m a c u la r a fe a . O b l i q u e c h o rio re tin a l fo ld t e s le n d e d
th ro u g h 1 he m a c u la r a re a . A n u m b e r (if fine- v e r y lighLJy
p ig m e n te d lin e * a n d s c atte re d sm ail w h ile nodules; '.a rro w ,
E3j w e re present o n lh e surface o f lh e leg io n . A n g io g r a p h y
s h o w e d e v id e n c e o f c h o rio re tin a l fold s o n lh e nasal side
o f lh e mass ( C l. A d ia g n o s is o f m e la n o m a w as m a d e , a n d
Lhe e y e w a s e n u c le a te d . V e rtica l sagittal s e c tim ol lh e e v e
re v e a le d s u b re tin a l tu m o r w ith a n o r.m g e inner surface s le d ­
d e d w iLh m u ltip le y e llo w -w h ile n o d u le s la rro w , D f . C u t sec­
tion re v e a le d that lh e lu m o r w a s w h ite a n d w a s c a u s e d b y
m assive ih ic k e n in g o f lh e sctera. T h e n o d u le s o n Lhe a n te rio r
surface (if th e Lu m o r w e re lyinj^ w ilh in Ihe c h o r o id , w h ic h
w a s d is p la c e d a n te rio rly b y the scleral tu m o r. L o w - p o w e r
p h o to m ic ro g ra p h s s h o w e d e x te n s iv e Ih ic k e n in g o f the p o s te ­
rior sclera w ith sea Lief e d fo c i o f g ra n u lo m a to u s in fla m m a tio n
I t :. T h e r e w e r e s c a lte re d ly m p h o id fo llic le s in the c h o r o id
a n d e p isc le ra l re g io n la ir o w ) . Th e s e large fo llic le s in tfiE c h o ­
ro id w e re re s p o n s ib le for lh e n o d u le s n o le d o n lh e Lu m o r
surface o p h E h a lm o s e o p ic a lly a n d grossly. H ig E i-p o w e r v ie w
o f Ihe cEboroid o t e r t y in g Lhe scleral m ass s h o w e d a foca l c o l­
lo d io n o f ly m p h o c y te s a n d a ridd el ike e le v a tio n o f Lbe p ig ­
m e n t e p ilh e liu m (a rro w , F ), w h ic h is b e lie v e d to c o rre s p o n d
w ith lh e fin e p ig m e n te d lin e s n o te d o p h th a lm o s c o p ic a EE y .
f t - -I: A 2 6 -y e a r-o ld w o m a n w ith ty p ic a l arthrilis associ­
a te d w ith psoriasis n o te d loss o f p a ra c e n tra l v is io n in Lhe
lig h l e y e . A n e le v a te d , five -d is c d ia m e te r, o ra n g e . suEjrelin a I
Liim o r w a s fo Lin d in fe rio r Lo Ihe m a c u la ( G i . T h e re w e re s e v ­
eral g fa y -w h ite n o d u le s la rro w i o n its surface. A n g io g r a p h y
re v e a le d sLa in in g o f lh e Lu m o r surface a n d d ila te d , le a k ­
in g retinal ca p illa ries as w e ll as c y s lo id m a c u la r e d e m a
a n d o p tic disc staining 13-1.>. N o L e s w e llin g a n d redness o f
lh e distal fing er jo in ts La n o w s , E). This d is trib u tio n o f p i n t
in v o lv e m e n l a n d p in in g o f the fin g e rn a ils Ib a l w a s p a rlly
o b s c u re d b y Lhe n a il p o lis h a re ty p ic a l o f p s o ria tic a rthritis.
U ltra s o n o g ra p h y w a s c o m p a tib Fe w ith p o s te rio r scleritis. T h e
h^sion d id not c h a n g e o v e r a 4 -y e a r p e rio d o f fo llo w -u p .
S u r g ic a E ly i n d u c e d n e c r o t i z i n g s c le r itis (SIN S).
| - L : This 2 0 -y e a r -o ld m a le d e v e lo p e d s eve re p a n u veitis
w ith vi I г i Li н in his lefL e y e . F a ilu re o f re s o lu tio n o f Lhe v itri-
Lis fo llo w in g h ig h doses o f steroids a n d im m u n o s u p p re s s iv e s
p r o m p te d a v itre c to m y . H e c o n tin u e d If) s h o w in fla m m a tio n
o f bis sclera, in spite o f im p ro v e m e n t o f vitre o u s in fla m m a ­
tio n , e s p e c ia lly a ro u n d lh e s c le ro to m y silos fo r a lm o s t a y e a r
( l - U H e w a s treated w ith m e th o lr e v ile a n d m y c o p h e n o la te
m o le til w h ic h s ta b ilis e d the scleriLis a fle r a lm o s t a vear.
CHOROIDAL SARCOIDOSIS
In lhe ocular fundus, sarcoidosis most frequently involves
the opiic nerve head, retina, and vitreous. iome patterns,
however, ш а| develop one or more focal sarcoid choroidal
granulomas, usually in lhe vicinity of the macular legion,
iome of these patients, who are typically young, often
black individuals, have other clinical evidence of sancold-
osis.^: ]hey experience blurred vision secondary lo a reti­
nal delachmenl overlying a nonpigmenled, usually slightly
elevated., yellowish white choroidal mass that simulates
closely thal of an amelanolic melanoma, metastatic carci­
noma.. tuberculoma, or other choroidal masses, including
choroidat osteomas (figure 11.Зб).596' 394 Patients with
such masses, particularly young adults, should be evalu­
ated for other evidence of sarcoidosis. These Lesions usu­
ally respond rather promptly to moderately high doses of
corticosteroids systemically (figure 1L3SG-I). A 56-year-
old black woman observed at the Uascom Palmer Lye
Institute clinic wilh biopsy-proven sarcoidosis and mini­
mal evidence of uveitis became legally blind because of
progressive choroidal neovascularization and sub retinal
nbrosES (figure L1.36J-J.].
M.36 Sarcoid choroiditis.
A a n d Б: M u ltifo c a l c h o r o id a l g ra n u lo m a s in а 2 9 -y e a r-
o id Ы лск Д о гн а л w ith a 1 -m o n th b is lo rv o f b h irre d
ti^ jo n a n d p h o to p s ia a n d я 2 -у е д г h is to ry o f d y s p n e a a n d
Ivn jf j h Jid e n o p a l by.
D - F : M u hi foca l c h o ro id a l g ra n u lo m a s in a 25 -yertr-o 1(3
m jim iin w ill: b i-opH V-p roven H a n co id o sii. К о 1я I b y large
les-ion s u p e rio r La lh e optic; disc; it a n d lh e h w >;m<il] k ^ io n s
(s n o w s , [J a n d F ). A l l o f lh e lesions tffespbndfid p r o m p tly lo
syHlem ic corLic-osleroid tre q tn ie n L
G - i : This 4 0 -y e a r-b ld w b r r w n d e v d o p e d Eilurnud v iH io n in
the ri^hl e y e a s s o c ia te d w ith m u ltip le c h o ro id a l g ra n u lo m a s .
Note? IК н I H im t1 a p p e a r n o n fiu o n e s c e n l iwhite? a r r o w t , I). S h e
h a d a la rg e &rea or c a p i l l a r n o rifjo rlu s io n 1 Й л р а г а ]|у s t t -
o n d a r y to a n o ld b ra n c h retinal v e in o c c lu s io n (a rro w , H ) .
) - L : PiTpgrE^siv-e c h o r o id a l neWasSqyl-arixaljjSfti a n d s u b re lin a l
fibrOeis in b o th e ye s o f n Eilack [M tie n l w ilh b io p s y -p r o v e d
sarcoid o sis. Loss o f v is io n in lh e k*fL e y e (K ) o c c u rre d ti years
b e fo re h e r p re s e n ta tio n w it h v is u a l loss in the ri^ b t e y e (Ji.
A n g io g ra p h y re v e a le d ju x la p a p illa r y c h o ro id a l n e o v a s c u la r-
ii a l io n I'Lj. In spite cl" p h o tu c u a g u la tio n , s h e b e c a m e le g a lly
b lin d b e c a u s e flf p rn g re s fiiw s u b re lin a l fib rosis.
I 'G - J , 'l u u r li.'s y u l [ J j . L h r v ld P o l lj .J
RETINAL AND OPTIC NERVE
SARCOIDOSIS
Sarcoidosis is j systemic noncasealing gmnulomalous
disease of unknown cause. Although il has protean clini­
cal manifestations il affects lhe pulmonary lymph nodes
and eye most pffen^00"405 Ocular InvolvemenL occurs
Ln approximately 40°/ii of patients wilh sarcoidosis and
is more frequent in blacks than in whiles. Anterior uve­
itis is more common than posterior fundus involvement,
fundus lesions more frequently involve lhe retina than
the choroid and may occur iit the absence of anterior uve­
itis and in patients wilh minimal or no olher evidence
of systemic disease. Characteristic fundoseopic findings
include perivenous exudation [Figure U.37A, С, P, and
ti) with candle iv ал-dripping exudate,1"1" 400 preretinal
and inlravilreal while nodules often arranged in a "siring
of pearls/4" focal superficial and deep retinal while
$odide$1*Q' ,',Q papilledema, nodular papillitis, optic neu­
ritis, and occasionally large white masses on the inner
surface of the retina and optic nerve head (Figures 11.38
and All of these lesions are caused by epi­
thelioid cel! proliferation (Figure
branch vein occlusion.’U " J|J |J| central relinal vein occl Li­
ston,41n large areas of capillary non perfusion, retinal nto-
vascularizalion. ,21~i2* vitreous hemorrhage, and oplic
disc neovascularization11rJ,42b may occur as complications
of the granulomatous periphlebitis and phlebitis [figure
11.ЗУ A). The neovascularization may resolve after treat­
ment tv ith anti-in lammatory agenta.436
KocaE granulomas may occur under the RPE (Figure
11.39C: and D) and within the choroid, '['he predomi­
nance o f Thelpet lymphocytes in the choroid and retinal
M .37 Sarcoidosis with phlebitis.
A - 1 : rhi-s ^ 5 -y fia r-o td A l r k a n A m u T ic n n W qtrian w a s a tfm it-
Led ta r in s p ira to ry distress fro m p re s u m e d fun^iii р п и и л ю -
П 1Л. H e r v is io n w as ld / 2 0 in t-43t.li e y e , a n d the lefl fu n d u s
s h o w e d m u lli focal p a riv e n o u H (.Lifting IA ri itlI O . H u o r e s L 'n l
fi п 11 n~: s h o w e d focal Lhn d o t h " I ial d e c o m p e n s a tio n ril the
sHesciE perivu n ou H c y ffjh ^ :li a n d D i . T w o later fu rth er
сliffu ы(? invoivciTTiunl ni [fie vlmiis w ilh several те И п а I h'Cimor-
rh ayes w.m seen (Ё ). T h e ri^ h t e ye w as n o w s im ila rly in v o lv e d
f C ) w ilh n o n p e rfu s io n o f the v e n o u s tributa ries f F j . A chest
C o m p tit^ d Com o^nitphv je a n re v e a le d b ilateral m n d ia s lin a l
a n d h ila r a d e n o p a lh y w ilh . c n le w ita lio n n n d a n ^ io le n s in -
c o n v e rtin g e n z y m e r e lu m e d m ild ly e le v a te d al 5 7 \\$f\ (n o r­
m al fi-5 2 V O r a ] p re d n is o n e bO теки lied in trn p to v e m e n l
[)F her re s p ira to ry staluh a r d fessoltilion o f Ihe phlEibiLis Ш
a n d 11 and nhe w a s tn a in ta if& rf o n H ) m ^ ni p re d n is o n e .
I<Jui irC-ечу (jf L)r. W illi,Lird iV u 'I'.t and IJr. 1чя;>1, IfcnuvccitEi. b nnd I, Abe..
V j h Приi J i L .th V rt | |L(.' L , I h e R r f l n a l A i t ^ S a U n d r jn 2 0 Ш , 5 7 B - D - 7 0 2 D -
3320-'J. p.275.>
infiltration suggests that sarcoidosis is a disease of height­
ened cellular immune response, particularly at the sites
of organ and tissue involvement.'1'’" 4'1'' Patients with sar­
coidosis confined to the choroid often experience loss of
central vision caused by a so Litar}' yellow-white choroidal
mass in the paracentral region that may simulate meta­
static carcinoma or an amelauotic melanoma [see figure
11.3&A—!) . Patients wilh multifocal sarcoid choroiditis
may simulate patients with M CP (pseiidp-POHS) and
birds hot chorioreliujtis.Jk,,'I J'J Subretinal neovasculariza­
tion and macular detachment occasionally complicate
sarcoid choroiditis.'1"1 Sarcoidosis may cause widespread
chorioretinal degeneration4JL and massive subretinal fibro­
sis. (see Figure 11.36J and K).
 Approximately 20-30% of patients with retinal mani­ I 1.33 Sarcoidosis or the retina, optic nerve, skin, and
festations of sarcoidosis will have evidence of CNS conjunctiva.
involvement (Figure Д —С : M acul-ar s in \f n p jic d is c s w e lli n g an d p e riv e n o u s "tjm -
Candle wax-dripping exudation, usually Accompa­ ( I V -.v■:(.>:-( I г :p in ^ ' j \ u d i :cs :n i ■■.■c.i'-с-!:. b l.u k m.n: w ilh
nied by pre relinal while exudates over the inferior fun­ b io p s y- p ro v e n s a rc o id o sis (A ). A r g io g r t t W rFfveflled lEvi-
dus [figures U.3SA and D, and 11.3УД, C, and D )r and d e n c e of p e riv e n o u s le a k a g e bl" d y e in b o lh eves l lj a n d O .

nodular papillitis (figures 1.1.3St1 ., f and \, and ]].ЗУА- D : P e rly tn o iJjj e x u d a tio n a h d m a c u la r s-lar in л 3 2 -y e a T -o ld
b la c k m a n Wilh b io p s y -p r o v e n Sa jg b id oS fs,
С, and !]]] are two signs thaL should strongly suggest the
E a n d F : Typ ica l SLirt:oid n o d u le s a t lh e righl o p tic disc ir>
diagnosis of sarcoidosis. ЧЪе diagnosis can be confirmed
,i 1 ] -y o a r -o I d b la c k m a n w ilh b io p s y - р г т е г т s a rc o id o sis .
by biopsy of affected lymph nodes, conjunctiva/^''"'11, V isu a l a c u ity in lh e lefl e ye w a s 211/2 0 0 . H e w a s I nea led
salivary glands,'^ and lacrimal gland, fewer than 5 % w ilh s ys te m ic c o rlic o s ie ro id ^ , a n d 6 n itiп 11ть bite* m o s l nr" the
of patients with sarcoidosis show cutaneous reaction to o p tic n e rv e h e a d g ra n u lo m a s (E) h a d d is a p p e a re d iF l.
tuberculin protein. Jhe chest roentgenogram or С Г scan G | p r e fe tir a J лсгкМем in л p a lie n l w ilh sa rc o id o sis .
shows evidence of sarcoidosis in over У0% of cases, '['here H : S a rc o id g ra n u fo m a ft o f 4 № W .
]r ia r c o id t;ranu3om a o f lh e c o n ju n t liva .
is a high incidence of elevation of angiotensin-converting
j a n d K : S a fc o jtio d ls o f lh e o p lic n w v e h e a d associaled w ilh
enzyme in patients With salcoidiails^0^'1'15,140 Ciallium
p rn m i пеги n o o v a s c u la ii z-at iorv
citrate uptake studies may be helpful :in confirming lhe L i ia n to a d p e rip h le b itis a n d p a p illitis in a puli ел I w ilh sar­
diagnosis. Demonstrating noncaseating granuloma in c o id m unin-^ilis.
a tissue biopsy is the only confirmatory lest for sarcoid. ■
L, iu rlnis у f j f U r . ' , ' i i l i i i i ii к С та и well ■
Ihese tests may return negative if the patient has already
heen empirically started on systemic steroids, and some­
times even topical steroids. Hence it is important to order
the ilives ligations prior lo starting therapy.
All of the lesions of sarcoidosis usually respond to treat­
ment with corticosteroids. lhe steroid dose required is
not veiy high and D.Sjng/kg body weighl is usually suf­
ficient. Because of the chronic nature of the disease, cor­
ticosteroids should be employed judiciously primarily
for an intmediate threat to loss of visual or olher vita!
organ, function. Occasionally, use of other agents such as
cyclosporine and methоtresale is required to control the
inflam m atio n ,i.o w -d o se methotrexate once a week
works v e r y well in patients with long standing Eow-grade
activity. Мусорhenolate mofelil and minocycline have
heen used.’ *''"1'11 Neovascularization of the optic disc may
show dramatic resolution following treatment with corti­
costeroids.'1'" H’hotocoagulalion may be helpful in control­
ling reLin<sl neovascularization in the peripheral fundus.
Multiple mechanism glaucoma often accompanies ocular
sarcoidosis, due lo trabeculitis or nodules in the angle in
the early stages, and peripheral anterior synechias pupil­
lary block from posterior synechiae and steroid induced
glaucoma in the chronic stages of the disease. Severe/
chronic cases require judicious use of steroids and immu­
nosuppressive agents, and manage men I of secondary caia-
racl and glaucoma with medications and surgery.'1

A C U T E IDI OPATHIC M UL T IF O C A L
INNER RETINITIS A N D
NEURORETINJTIS
I'hese patienls are typically children or young adults who
soon after a viral-like illness develop loss of vision usually
in one eye associaled with one or more white foci o f acute
retinitis and neuroielinilis In one or both eyes
lbe acute retinal lesions primarily involve the Inner
half of the retina and show sojne predilection for occur­
ring adjacent to major retinal arteries and veins. In this
latter location they may cause branch retinal artery or
w in obstruction, which, together with oplic nerve head
involvement, are the major causes of symptoms in these
palients (Figure 10.O4). At the time of eye eita mi nation
the patient is usually afebrile. .Blood cullures and medi­
cal evaluation are usually unremarkable. Some of these
patients have a clinical history of a cat scratch and sero­
logic evidence of cat-scratch disease. ’ [ See discussion
on pp. Й0Й and 12У0 and Figures 10.04 and 1!>.]!.} One
patient had serologic evidence of influenza A infection.-1
l?ept$piTii organisms Were cult tired from the spinal tin id of
another patient. !
W ithin a week o f involvement of the optic nerve head,
a macular star figure usually becomes evident. Those pre­
senting with branch relinal artery occlusion usually have
a permanent scotoma, but most patients with retinal and
optic nerve head involvement recover normal or nearly
normal visual acuity spontaneously. A few may develop
evidence of optic atrophy. Jhe value of corticosteroid and
antibiotic treatment is uncertain.
The fundus picture in patients wilh acute idiopathic
multifocal inner retinitis and neuroretinitis may simu­
late that seen in patients wilh retinitis and neuroretinitis
caused by pyogenic bacteria (Figure 10.01), fungi, syphilis,
and toxoplasmosis. Salients with evidence o f branch reti­
nal artery occlusion may simulate palients wilh bilateral
idiopathic recurrent branch relinal artery occlusion (see
figures 6.19-6.21).
I 1.39 O c u la r a n d c e n lr a l n e rv o u s system sarco id o sis;
cli n ic o pa lh ologi с c o r re la lio n .
A -F: r h ii 3 Й-уеаг-old black тлил haq cenlral nervous system
sarcoidosis associated with bilalera! relinal and optic r e f i t
5&rtqjdo5is. Fundus painting :Ai showed granulomas on the
oplic disc, along lhe relinal veins, and in thy vitreous interi­
orly |ljiset^ [here1 was a branch vein occlusion in [Iiej infero-
lemporal ■|.i. ilI_.1171. The patient died several monlh* laler,
and histopathologic exam ination revealed multiple peri­
venous g ^ ru jb rm s wfth extension o f the granulomatous
read ion inlo the overlying vitreous in Ihe juxlapapillary area
(B) and the peripheral retina (CI and E). N cte lh e jjranuloma-
tpus reaction surrounding the retinal veins; (arrows, С and
t3 and extension of Ihe ^ranulomalous геле Iion benealh lhe
tetinal pigmenl epithelium fC and [].. I here were m ulliple
granulomas in lhe pre- and m lla m itrd r parts ol the optii
nerve fF anti throughout lhe cenlral nervous system.
C - L r l'h-is 4 5-year-old Indian wom an suffered a sudden-
onsel painless progressive loss of vision associated w ilh
head lithe for 20 days in bolh eyes. She was diabelic and
hypertensive. H e r vision was 2(У400 in bolh eyes. She had
1 + cell and ftare in both eyes w ilh posterior synechiae
and pigment on the anlerior lens surface. She had bilaleral
nodular elevalion ot the optic discs and peripapillary hem­
orrhages. areas ol decreased axoplasmic flow, and a m acu­
lar slar w ilh m acular subrelinal fluid (G and H). K w iu w of
systems was posilive for malaise, body ache, and shortness
of breath, ^he denied fever, rash, unprotected sox, lubencu-
losis, and ischem ic heart disease. She had no pets, iyslem ii
ека mi nation revealed bilateral iine crepilations and tiepa-
tosplenomcgalv. Her tulrerculosis skin test was negative,
sedimentation rate was 24m m r and angiotensin-convert-
injj enzym e level was 35-.5 |щ/1 Inormaf 8-52]. Chest X-ray
revealed hilar lymphadenopathy and nodular opacities in Ihe
parenchyma, Г.'отри I ed tomography scan revealed pleural
and inlerslilfal thickening and enlarged hilar lymph nodes
fl). A Iransbronchial lym phnode biopsy showed non casea ling
granuloma suggeslinu sarcoidosis (Jl. Abdominal ultrasound
revealed hepaLosplenomegaly w ith areas of tatty change in
the liver. She received oral prednisone frOmg and topical sle-
roids and cycloplegics in bolh eyes. By -f rtipnths iier vision
had improved lo in both eyes, and lhe iridocy( litis and
disc edema had resolved with a le w resolving ex и da Les (K
and L j .
lA-t, k;iri: ( л Ц pnd LJlMin.’ -' G |ii L. louHusv ol Ur. Vish.ili Си|э(а ,hn<l
Dr. Arnucf k_im(:■I.'i-.
" - ъ 'Г'■ -*;1
\ . ■ ’

■* ■* Ъь& Г* . ■
BEHCET'S DISEASE
J
Behcet's disease is a chronic systemic disease o f unknown
cau.se characterized clinically by aphthous ulcers o f the
mouth and genitalia (Ngure 11.40A and 1>), intraocular
inflammation.. nondestructive иго negative arthritis. ,md
cutaneous vasculitis including erythema nodosum [figure
ll^ O B ):10"1' ^ ihe criteria for diagnosis include oral aph­
thae or genital ulcers in association with any other two o f
the sis major manifestations o f the disease, 'i'he disease
occurs mosl frequently in people of Lhe Mediterranean
hasiti and Japan, in approximately tit№b o f patients the
ocular disease is bilateral, and it is twice .is frequent in
men.4 1 Behcet's disease has been reported with less fre­
quency in the LJ5A, where the sex difference in regard Lo
ocular involvement has been less pronounced."'" Iritis and
vitreous inflammatory cell infiltration are present in nearly
all patients with ocular involvement. !n mosL cases the
iritis is nongranulomatous. Hypopyon occurs occasion­
ally (1'igure U.40CJ. hdema o f the macula and optic disc.,
patches o f gray thickened retina, focal accumulations o f
yellow-white deep retina! exudates (figure ] ] .4 LЛ —С and
H), scattered areas of delicate pigment clumping, perivas­
culitis, central and branch venous and arterial occlusions
(figure 11.42), papilledema, papillitis, and optic atrophy
may occur [figures 11.401, Ц G, and L and ]l 41}+Visual
Loss is usually caused by long-standing retinitis, retinal
infarction, relinal arterial attenuation.. cystoid macular
edema, and, in some cases, retinitis proliferans and vitre­
ous hemorrhage.'"1J:"' Whereas progressive optic atrophy
may accompany the retinal changes, acuLe loss o f vision
caused by optic neuropathy without retina\ involvement
rarely occurs in patients with Behcet's disease. "'” l
During an acute attack the erythrocyte sedimenta­
tion rate, acute-phase proteins, and circulating immune
complexes may be elevated along with dramatic altera­
tions of serum complement levels.1'4' 1" ' ' 1^' Elevation o f
M .4fl Be heel's disease.
A: Aphthous u k c r (arrow).
В: fcrythema n o d iK in i of lower legs.
C: Hypopyon.
D - b Гhis 31-yeaf-old wom an wiLh Beb^utJs disease bad
aphthous и Icers ! arrow, Г.ИГ m ulliple foci of rulinitis fcaiising
branch retina] arlw y occlusion I arrow.. tf)f and branch reLi-
nal vein occlusion (arrow, Fj when she initially presented.
O ne w eek Cater s-be developed another branch retinal artery
occlusion tanow, G —t) in the lefl ™ a .
|-L: Ibis -year-old man with aphthous stomatitis and
hypopyon (C) in the riybt eye had bilateral vilrilis, multiple
relinal fschenuc patches, and hemonba^es (|j. His visual
acuity was counting finders in the rifjhl eye and 20/25 in
Ifie lefl eye. Angiography revealed periva-scular leakage of
fluorescein (K). ForTy-Iwo monlbs later his acui]y was 7/200.
Note Lhe pallor ol" the optic discr marked narrowing and
nheaLhin^ of Lhe relinal vessels, and a m acular scar flj.
strum concentration of interleukin-2 receptor. OX and
complement-reactive protein may occur in all forms of
lhe disease4C,'J"‘l7i,iiej'j8?-'4M Antibodies against the vascu­
lar endoihelial cells and mucosa can be demonstrated in
some patients with Behcet's disease.Ш -,|Н' ;" 1' Antibody
affinity lo retinal 5 antigen Is lowered.1'
A generalised vasculitis is responsible for the multipli­
city o f clinical manifestations. Neurological manifestations
can he seen in Neuro Behcet's. Activated T lymphocytes
and hyalinized thickening are found in association with
the retinal and optic nerve perivasculitis."" Although a
virus was implicated early in the history of Reh^efs dis­
ease,"'1 the disease's cause is unknown. 'L'he increased
incidence o f HLA-B5 or -E5w5t antigens in patients with
Behcet's disease in the Middle East arid Japan suggests that
susceptibility genes lo the disease may have been spread
by the old nomadic tribes о г ЧЪ гЬб via the silk roule_4H,m
lliese antigens are found less frequently in patients in the
United States with lie beet's disease.
 Since Behcet's disease is a chronic disorder character­ И .41 Be hce Vs disea se.
ized by spontaneous remissions and exacerbations and
A-1: This 50-year-old m;in wiis LreaLed elsftwhere i'oj recur-
since the course of the disease varies from one patient lo renl iridocyclitis in huLh eyes fo* the previous 2 monlhs. He
another, the evaluation of therapy is difficult. Topical and Lhert « fv e lo p td bilateral Tripirlly progressive pan uveitis w ilh
oral corticosteroids constitute (he first line of treatment in vitritEs, patchy retinal w h iten in g and retinal hemorrhages
these patients. Jn severe cases these haw been combined w ilh n visual dec. I inti Lo 20/20(5 in lh e ri^hl eye and counL
with cytotoxic agents, including azathloprlne, chloraan- finders in lhe lefl eye. l-le w as referred in With a diagnosis
c f acute bilateral relinal necrusis. Examination revealed
hucil, or cydophosphamide.'l7', l t J ''1'1' I t t e s e drugs
in uItifocaI retina Г infarcLs, and diEEuse relinal arlerial and
may be used in concert with immunostimulation agents,
venous leakage I A—E Keview of symptoms revealed a his-
including levaimsole and colchicine.'1434 Cydosporine Л, Lotv of recurrent aphlhuub ulcers, o n t cipisudc of $emLal
a specific an Li-T-cel E medication, has been used success­ ulcer, and arthritis involving his 4tnee and IhumE). Л diagnosis
fully in some Ibese latter agenls oE E^hteL's disease? was made and he was LreaLed w ilh oral
should be employed only in severe cases because compli­ steroids followed by cyclospurine. Bilateral m acular holes
cations may be severe.'11' 'l"' Plasma exchange may reduce occurred following resolulion o f lhe relinilis; lhe uveitis ULfh-
sided over а у ваг alter a few episodes ol" recurrences (F-W.
ocular in f animation caused by ESehcefs disease in patients
Thu righl eye underwent m acular fiole repair wich dosure I :
unresponsive to standard medical therapy5( 1A controlLed
Lhe left was nol operaEed on due Eo severe m acular iscfiemLa.
clinical trial demonstrated the safety and effectiveness of
azalhioprine in reducing the frequency of hypopyon uve­
itis,- aphthous ulcers, and arthritis. Inlerferon-alpha
has been advocated in fiurope. "M and more recently
monthly or bimonthly tumor necrosis factor-alpha Inhibi­
tors such as etanercepL, Infliximab, and adallmumab."
Mycophenolale mofetiE can also be used when other Lreat-
ments fail. "
The differentia! diagnosis includes sarcoidosis, the acule
retinal necrosis syndrome, diffuse unilaleral sub acute neu-
rorelinltiSr Idiopathic vitritis, pars planitis, vitlliginous
chorioretinitis, and reticulum cell sarcoma.
 i l

i
*
■■

w
r
О

DIFFUSE, C H R O N I C
N O N N E C R O T I Z I N G RETINITIS,
VITRITIS, A N D C Y S T O I D M A C U L A R
ED E M A
Jhe permeability ol" the retinal capillaries, particularly
Lbose in the macular region,, may be affected by chronic
diffuse lAflHtimation involving the retina And vitreous.
Al plough these patients may be categorized into several
different syndromes,- in none is the cause known, nor can
it be established whether the primary tissue involved is (tie
retina or (he vitreous. The clinical features shared by these
patients include complaints of floaters caused by inflam­
M .42 S e v e r e a s y m m e t r i c B e h c e t ' s d i s e a s e .
A 43-year-aljJ wuman with pan I history of dm I and vaginal
uJcers, arlhriLisi, and Kkin llI ceja Iion previously cofitftti-led
with colchicine and £Lera ids., developed right optic neuritis
iA. and a positive lluoruscunl Treponemal <m(ihorJy absorp­
tion. Гhe left eye was- Lin involved (Ы. Nine monlhs; laler
vision in the right eye dropped to no lighl perception and
was associated with phlebitis ol the left leg. Complete mas-
sivr in fare Iion of her righl optic nerve and diffuse retinal
hemorrhages were noLed fCl. ^>or perfusion of lhe righl fun-
■H1.1:=
■was seen by angiography IL> and Ei; lOOm^ prednisone
and l.im g methutrekate were ;tdded. Thu righl oplic nerve
and vessels turned white over the next 2 monlhs (F and 0):
The left eve remained un involved (Н]. N'oovaKcularizL-itaofi of
tfie optic dine occurred o v e r! i me It!:.

matory cell infiltration o f the vitreous and loss o f cen­ if jl lUrtL'ay fif U r. I J.IV 11 I-ric h e r .
tral vision caused by cystoid macular edema in eyes that
externalLy show no signs of inflammation. Some degree
o f papilledema iitay be present. Hi lateral involvement is
the rule. A few retinal hemorrhages often occur periph­
erally. Evidence of peripheral retinal degeneration with
some disturbance of the underlying pPE is seen eventually.
Narrowing o f the retinal vessels and pallor of the optic
disc along with complaints o f night blindness may occur
tn some cases. Retinal holes, retinal detach mem, and pre­
retina] vitreous Enembrane formation occur occasionally.
Jhe vitreous inflammation and cystoid macular edema
often respond poorly lo corticosteroids or other therapy.
'i'hese palients may be subdivided into three major clin­
ical syndromes: [1] pars pi an it is; (2) idiopalhic vitritis;
and (3) vitiliginous (birdshot) chorioretinitis.
D ifFiitv, Chronic Nou\wc:f\<Hzi}ifi RrtH ritis, Ш г /frs, njj;l C ystaid M nciilHfr Eth'wn 10 3 5
RETINITIS A N D VITRITIS WITH
V IT R E O U S BASE O R G A N I Z A T I O N
(PARS PLANITIS, PERIPHERAL
UVEITIS, O R C H R O N I C
CYCLITIS)
lh e term "'pare planilis" has been used Lo describe
patients with chronic vitritis who develop snow-bank
exudates and vitreous condemnlLon overlytrtg the peri p li­
enll retina and pars plana, usually inferiorly in both eyes
(Ligure ]] .43]. " ■ These palients are typically chil­
dren or young adults of both sexes in excelLetil general
health when they develop floalers and blurred vision,
lhe eyes are white. Л few patients may have fine ke rati lie
precipitates. .Fine and coarse vitreous floaters are present
and may be responsible for moderate loss of visual acu­
ity. Snowball preretinal aggregates similar to those seen
in sarcoidosis may be present (Figure 1L.4ЛЕIJ. Macular
edema is the most common complication o f the disease-
and it may persist despite vigorous corticosteroid therapy
(E'igure П.43В and C). Dilation o f the Enajor retinal ves­
sels, particularly the veins; sheathing o f the retinal veins;
and varying degrees o f papilledema often accompany (he
macular edema [E-'igure 11.43B and (J). Other complica­
tions include second ary cataract, secondary glaucoma,
sheathing and narrowing o f the peripheral retinal vessels,
traction and rhegmatogenous delachmenl of the periph­
eral retina,''1" retinoschisis, 4:4 sub retinal neovasculariza­
tion,.^" neovascularization o f the optic d is c '' and retina
(E'igure 1 Ы ЗЬ - С ], '■ ' pseudogliomatous angioma for­
m a tio n ,''’ vitreous hemorrhage, rhegmatogenous retinal
detachment, ■'J heterochromia irides, band keratopathy,
and rarely phthisis bulbi. lh e disease is chronic but is sub­
ject to remissions and exacerbations. Lhe amount o f pars
plana exudate generally correlates with Lhe severiLy o f vit­
reous inflammation and cystoid macular edema. Vlost
patients maintain useful vision in one or both eyes. Eyes
with complete posterior vitreous separation may haw a
belter visual prognosis.'"1 'there is some tendency for the
disease to lessen in severity over a period o f many years. '
fluorescein angiography demonstrates a variable degree
of permeability alterations of lhe capillaries o f the ret­
ina and optic disc (I'igure 11.43C}..11 En patients with
macular edema ihere Is usually angiographic evidence
o f widespread relinal edemar papilledema, and in some
patients late staining of the larger retinal w ins and venules
(E'igure I3.43C and (i). Most patients haw electroretino-
graphic abnormalities, such as delayed b-wave implicit
Lime, abnormal response lo flicker and reduced b-wave
oscillations. '1:
The limited histopathologic data available suggest that
Lbis disease is a chronic nongranulomatous inflammation
involving primarily the retina and vitreous.4 '
lhe fluffy snow-bank opacities peripherally are probably
caused primarily by cellular infill rate within the vitreous.
И .43 Pars plamtis.
A: Hundus drawing showing usual dislribLFtitin tiff sntJw -Езлпк
cn/er Lhe pgps plana mteriorlv.
B-D: I his 17-yaar-DId wumaTi with pars planilrs nolud loss
ot vision because of cy^taid т л е й Ini edema :B And (Ij. Kour
months laLeT, aPler svslem it carticoslefaid tm fapy, the edema
had resolved ID:.
E - C r EieJinrLis proliferans (arrows^ in the macular атеа of л
3 1-year-old mail w ilh pars planitLs. Angiography dcmt)n-
slraled 1елк^^е o f fluorescein from these vessels and cystoid
mac и I ar edema (f and C ).
H iind I: Preretircal nodules (H| and cystoid т л cuIяг edoma
(I) w ere present bilaterally in this 32-year-oEd wom an w ilh
snow-bank EH udate'tin lhe pa*s pi л г>л.
|—L: Pflfs planFlis associated w ith mu I Li focal choroiditis,
macLrtaf edema, papilledema, vitritis, and anLeiitw Lrveitis
in a П -year-old male vtilh J-year hislory ot phtHophubia,
H o a lB ii and vis-ил I loss. Genera] physical SxamitiStio^ Was
negative except for axillary (tfitipJtadeniteaLhy. biopsy of the
nodes revealed granuloma Lous inflammation ol unknown
cause. Serologic Lesls for toxoplasmosis, syphi Iisr and Lyme
disease w ere negative. l'realmonl w ilh syslEmik irorlicosJe-
noids and doxycyclfrte produced minimal improvement.
IA . I w i n W u l c l i . ,|J '>■ A n w n и -.in M e d i L i i l .- Y s M jr u lu jn . A l l r i ^ h t i
ffeervied. 1
Later this fluffy appearance may he replaced by less ele­
vated, white, organized scar tissue, which may be derived
from gEial elements o f the peripheral retina.5 Prominent
perivenous and venous infiltration occurs wilh lym pho-
cyles that are predominantly T-helper lymphocytes.-’^ The
uveal tract is relatively free tif inflammation.''''1
'lhe pathogenesis of pars plauitis is unknown, lhe
development o f a migrating comeal endothelial rejection
line (autoimmune endotheliopathy) in some palients with
pars pEaniLis suggests the possibility that the disorder may
be an autoimmune process directed toward the vitreous.-"M
Some o f these palients show improvement in visual
function following oral corticosteroid therapy. Many oth­
ers, however fail lo respond to this therapy, which should
be used sparingly because o f the disease's chronic nature
and its tendency to undergo remissions and exacerba­
tions. En the presence of useful cenlral vision it Is probably
unwise to treat these patients with long-term corticoste­
roids. lhe value o f cyclodiathermy and cyclocryotberapy in
treating lhe pars plana and peripheral retina is conLrover-
j^ j sjj.sia.s^ -[hese cyclodestmctive procedures appear lo
be of mosl benefit En those patients unresponsive to cor­
ticosteroid therapy and who in addition have neovascular­
ization in the region of lhe vitreous base.'111■ ' l he reason
for accumulation of exudate over lhe pars plana predom­
inantly in the inferior fundus is unknown; il is probably
more a function of gravitational forces than locus o f the
disease, '['he value of vitrectomy in treating cystoid macu­
lar edema is also uncertain.0'^ Although some success
has been reported utilizing combination iherapy of cor­
ticosteroids with anlimetabolites, the value of this treat­
ment in the long-term managentenl o f these patients is
uncertain. 5 2 P - 5 3 0 S 7 lliere are significant risks in such
l j
treatment, and therefore it should be employed only in
p.ulienti with severe involvement.
'Jbe differential diagnosis includes sarcoidosis, periph­
eral toxoplasmosis, Behcet's syndrome, ТЬхйййъ Cdjmj,
□cute recurring cyclilis, and the pseudo-laO [ lb. Gass has
seen 3 children with Lhis latter syndrome who in addition
had dense fthife pars plana exudate and who developed
Eoss of macular function secondary to choroidal neovas­
cularization and disciform detachment.11^ Lyme disease
may be associated wilh pais planilis and anterior uveitis
(see Figure 10.UGA-F}.
Pars planitis has occurred in multiple members of
at least eight families.51^ Pars planitis has
occurred in patients developing evidence o f demyeLinal-
ing d i s e a s e . ’J9-SSJ д long-term follow-up of patients
wilh pars pLanitis revealed that optic neuritis developed in
4 patients (7 .4% ) and multiple sclerosis in an additional S
palients (14.fl% ). i1 Ibis same group found a n associalion
o f HLA-DR2 in 67.5% o f patients wilh pars planilis (28%
controls), and they cited others who had found ША-1.Ж2
id SO-7!>% of North Americans and Europeans with mul­
tiple sclerosis (20-25% controls).'1,IJ- 52
IDIOPATHIC DIFFUSE
N O N N E C R O T I Z I N G RETINITIS
W I T H O U T V I T R E O U S BASE
O R G A N I Z A T I O N (IDIOPATHIC
AGE-RELATED V1TRITIS)______________
The most frequently encountered group patienls with
floaters or loss o f vision secondary lo chronic vitritis
and diffuse retinitis are healthy middle-aged or elderly
palientSr most frequently women, who develop cysloid
macular as wet I as diffuse retinal edemar in some cases
papilledema, and cellular infiltrate o f lhe vitreous with­
out any evidence of snow-bank pars plana deposits {figure
lI^ i4 )L55,"55:f Cellophane maculopalhy caused hy an
epi retina I membrane is frequently present in the macular
areas, l-.xternally the eyes are quiet. 'Lhe peripheral fundi
often show evidence of narrowing and sheathing o f the
retinal vessels as Well as irregular derangement o f the RPtL
Relinal edema and vitritis often respond poorly to cortico­
steroids or other therapy, t h e cause is unknown. Cass has
seen idiopathic vitritis in identical twins (i'igure 11.44 b-
lien nett and coworkers reported a large family with
autosomal-dominant adull-onsel vitreous inflammation,
selective loss o f the LRG h-wave, mild anterior-chamber
in flam matron, and laler retinal scarring, pigmentation,
peripheral retinal vascular closurc. peripheral retinal neo­
vascularization, vitreous hemorrhage, and cystoid macular
edema.'56
Patients with idiopathic vitritis share many features in
common wilh patienls with vililiginous chorioretinitis
I 1.44 Diffuse nonnecrotizing retinitis. vElritis, and
cystoid macular edema without pars plana exudation
(idiopathic age-related vitritis).
A-1}: This 70-year-old wom an noLtid fEealers and visual Idss
in ЕкиЬ eyes aL Co years nf л]це. Visual a-:.Liily was 20/200 in
Lhe ri^iht ey'e and 20-'!)0 in the left eye. She had hi lateral vitri-
Ii!d. rystoid m acular edema, and diffuse retinal edema. Note
an^ioj^aphic evidence of i-rrujjular fbcal suirs in Ihe periph­
ery and lhe mullil[)cu3aled fluorescein staininj; рдМегп in
the extramacular ли well as lh e m acular area iP-П ). She has
been observed for 21 years, and her acuily and findings are
unchanged.
E and F: Cystoid m acular edema, miTd papilledema, and vit-
liLii in a 59-year-old w i'm iin whose visual acuity was 2Q/-E0
in lhe ri^hl eye and 20,400 in Lhe left eye.
С —I: The identical I w in sister of Ihe palienl illtislraled m
h and F with the н а т е tondilion in both eves. Note the
marked retinal capillary dilalion (H ) and the ex.tramacu-
lar and I t i k l W polycystic edema (I I. Jiulh Iw in t noted Ihe
unsel o f Ftoalers and hrkjfred vision a I /50 years ol aj^e. Bulh
have markedly subnormal nod and cone eledrunneljnd^Taphic
responses.
(see next subsection). Differentiating patienls wilh idio­
pathic vitritis from patienls with genetically determined
retinitis pigmentosa sine ptgmento is difficult. The elec-
irorelinograpbic abnormalities are usually less severe in
patienls with idiopathic vitritis. Other disorders that may
simulate idiopathic vitritis include Whipple's disease (see
p. 930), laige-cell non-Hodgkin's lymphoma (see p. 1150),
metastatic carcinoma and melanoma to the vitreous (see
chapter 13), and lymphocytic in filtration o f lhe vitreous
associated with X-linked immunodeficiency wilh increased
immunoglobulin M / 57
VITILIGINOUS CHORIORETINITIS
AND BIRDSHOT
RETINOCHOROIDOPATHY
lhe syndrome o f birdsbol retinochoroidopathy or viti-
liginous chorioretinitis is characterized by: { I ) onset, in
apparently healthy patientsr both men and women in the
fifth to seventh decade o f life, of floaters, photopsia, and
blurred visionr often followed later by night blindness and
color blindness; (2) vitreous inflammation; (3) multifocal
patches o f depigmentaiion first occurring in the choroid
and later the RPli in the postequalorial fundi; (4) varying
degrees o f retinal edema and papilledema, and narrowing
of the retina Vessels and mild optic atrophy; (5) moder­
ate to severe electrorelinographic abnormalities; (6) a vari­
able rate of progression and severity bul wilh a tendency
toward stabilization and preservation of good central
vision in al least one eye; and (7J strong association with
]E E A - A 2 9 .^ H- ^ fi
 Lie fore the initial publication o f this syndrome., called
birdshot retinochoroidopathy by Ryan and М ^ ш е п е ^ ^ 9
the name Vililiginous chorioretinitis1' had been used at
the fiasco m Palmer liye Institute to describe patients with
this syndrome. 'Ihe author chose this name for this syn­
drome because of (he similarity in lhe appearance and
evolution of the patches of choroidal depigmentalion
Lo those occurring in the skin o f pa tie tils with У1ШЦда.4&0
lhese orange or yellow it]-defined patches, which may
not be present when the patient ii seen initially wilh vit­
reous cells and macu]ar edema, are typically scattered in
the postequa tonal portion o f Lhe fundus (figures 11.45
and U.46). '[hey are most numerous in a broad area sur­
rounding Lhe nasal two-thirds of lhe oplic clis.c and early
in the course o f the disease are often absent in the macu­
lar area. The patches vary in size and shape. Many o f lhe
pitches are round lo oval, bonie are irregular or elongated.,
often in a pattern lhal radiates toxvard lhe peripheral
fundus (I'igure 11.45A and Б). Striking and characteris­
tic features of these patches are the absence of hyperpig-
menlation within or at their margins and the absence o f
siit-1amp evidence bf thinning o f either the retina or the
choroid in the area o f depigmentalion. Large choroidal
blood vessels are often visible within these lesions, and
the overlying retinal vessels appear normal. During the
early stages of depigmentation.. particularly when associ­
ated with severe vitreous inflammation, absence o f vis­
ible choroidal vessels within these lesions may then
give the appearance of nonelevated choroidal inflam­
matory infiltrates. Angiographically in their early evolu­
tion these patches show no abnormality (I'igure 11.45C).
lhe lesions are usually symmetrically distributed in both
eyes. En time the patches enlarge and may be associated
with bio microscopic and angiographic evidence ofdepig-
menlalion and atrophy of the overlying RE1К and retina.
Ilyperpigmentalion may occur in some lesions in the late
stages of the disease, l.oss o f central vision may be caused
by cystoid macular edema (ligure 11.45E), by atrophy o f
[he retina associated with the depigmenlation of the RPfc
and choroid (i'igure 11.45F}, and occasionally by serous
macular detachment (E'igure II .45-Cj and I E) or by cho­
roidal neovascularization (Figure 1L.4&I3 and lj. ,V!,‘ ,f'4
I Proliferation o f new vessels from the optic disc and retina
may occasionally occur and cause vitreous hemorrhage
(t-'igure !I.4 6 |- L and ] ] .47 J. Etare associations with viti-
Liginous chorioretinitis include hearing loss^'J and Lyme
disease/™
fluorescein angiography may shoxv evidence o f delay
in Lhe retinal artery appearance timer increased retinal
circulation lime, and varying degrees o f unexplained
quenching o f fluorescence o f the retinal vessels dur­
ing the cour&e o f angiography.'1,(1 M ild vascular leakage,
more from Lhe veins than arteries, and cystoid macular
edema can be seen in eyes with active inflammation and
vitritis. Dark choroidal patches are seen on ICG angiogra­
phy; their significance is not completely understood. It is
likely Lhe iluorescein is blocked by choroidal lymphocylic
I - . 4 ? VEtiliginous chorioretinitis^
A -С: This 53-year-old wom an com plained ol Floaters and
had a visual acu ilv of 20/20. Ihort! w ere 2 - viLruous cells. A
similar mLtem oi mu Hi focal areas of yeNowish depigmenla-
Lifjn of 1It-e.*-choroid was present in bom eyes (A and B), Note
relative sharing of I he m acular areas, and elongation of lhe
more peripheral lesions. ta lly phases of ^Jjgiagtaphy showed
no abnorm ality in lb e region of these patcEws (com pare В
and Cj.
D - Fr Thji 50-year-old man rap ericanted floaters and mild
Eoss o f vision. O n ly a few small viLiliyinous patches were
t'-videnl in Lbe ju^Lapapillary area (Did H e had апдкэдтарЫ(
[evidence of cystoid macular edema it). Two years EalerJ his
visual acuity was 2CV4QQ and he bad manv ( й № vilili^inous
patches LEiroujjhoul bolEt Eundi (F)k
G rand H : This 49-y|6afdd wom an complained of fluaLers,
blurred vision, and melamorphopsia in bolh eyes w hen she
was initially examined In February Bilateral serous
delachment of the macula was pjetenl. TЕ>гь resolved spon­
taneously. W h e n seen at Bascum h^iimer Eiye LnstiLuLe 2 years
later she com plained o f nyctalopia and loss of color vision.
She bud vilneous ifjlls.., pigment motllin^ ai the macula, rand
widespread vftiligEnous patches throughout thte postequatorial
fund w ilb rtilaLive sparing of the macular areas i£"t and H i.
[jV - F ; f r u m O . i s s " 1s 1 1 Ч Н Г . A m L r i ( .tn M e d i C q l A h u c l i U o i i . A l l
rtSCrVeJ.I
infiltrates and inflammation rather than choroidal vascu­
lar insufficiency. Karly Ln (he course of the disease elec-
irorelinograpby may be borraal. Later, it shows moderate
lo severe abnormality in rod and cone function tn both
eyes of most patients. 1 ' ,J lh e rod function is affecLed
first. The electro-oculogram may be either normal or sub­
normal. Dark adaptation studies may show subnormal
rod function. D C !' over the choroidal Lesions is usually
normal unless the RPH ii atrophic; Lhen Lhe photorecep­
tors may also be disrupted.' ' bn ha need depth i magi tig
OCT may offer some insight into choroidal involvement.
Autofluorescence imaging is variable depending on Lhe
severity ofKE’Ei involvement, ihe oval choroidal lesions do
not show abnormal aulofluorescence. However the areas
where the overlying RPE is disturbed will show decreased
auto fluorescence. Sometimes Lbese spots are along the reti­
na! vessels, especially the large veins., giving it an appear­
ance of perivenous atrophy (figure 11.4SA and B),
i iistopathology o f a 43-year-old male wilh at leasl
a 6-year history of birdshot choroiditis not previously
treated with steroids or immunosuppressives showed mul­
tiple foci of lymphocytes at different levels o f the choroid.,
occasionally associated with hemorrhage, plasma cells,
and epithelioid cells. Some foci were adjacent lo choroidal
vascular channels. Eli ere was no necrosis. ГНё КГ1:, ciliary
body, nind iris did not appear Lo be involved. Other foci of
lymphocytes were found around some o f Lhe retinal blood
vessels and in the prelaminar optic disc.. Ihe lymphocytes
were primarily CDB1 T lymphocytes, with fewer CD4i T
and li lymphocytes.-' '
 Although <^ass observed multiple depigmented spots on
the arms and legs of several patients t'-iLb vililiginous cho­
rioretinitis, these appear to be more closely related to idio­
pathic guttate hypomelanosis Lhan vitiligo. I his former
disease is a common skin change of unknown origin and
simitar in bolh its clinical and histopathologic appearance to
^tfligo.sr6j|'i$bfit and associ ales'observed, Ъ patients with
cutaneous vitiligo and a fundus picture that appeared similar
to vililiginous chorioretinitis. Depigmenlalion (if the cho­
roid and ftFE similar to that seen in vililiginous choroidilis
may occur Ln patients yfitH other ocular diseases that may be
associated with vitiligo [VKH disease sympathetic uveitis,
and acute VKii-like uveitis caused by metastatic cutaneous
ц1е1апота]. l his suggests the possibility of a common auto­
immune mechanism.■ " 5Й0 Progressive degeneration of
Lhe peripheral retina, retinal artery narrowing, and optic disc
pallor and night blindness are features that may occur Ln all
four diseases. Vitiliginous chorioretinitis is usually a chronic.,
slowly progressive disease that is subject Lo remissions and
exacerbations. Most patienls retain useful central vision in at
least one eye for many years.
Treatment includes systemic steroids along with, or fol­
lowed byr immunosuppressives based on the severity of the
disease at presentation. If the disease Is active wilh vitritis..
cystoid macular edema, and retinal vascular breakdown.,
systemic steroids at approximately mg/kg are recom­
mended. Simultaneous institution of immunosuppres­
sives, such as methotrexate starLing at it}mg once a week
and gradually increasing to 15 or 20mg based on response,
is also recommended such that it becomes effective by the
Lime the steriod taper begins. Mycophenolale mofelil is
an alternative if methotrexate is not effective or not toler­
ated. l.ow-dose cyclosponne (2.5-5mg/kg daily}, wilh or
without other corticosteroid-sparing immunosuppressive
agents, has been used as an alternative to long-term corti­
costeroids.'''1 A recent report of use of daclizumab in those
refractory to mycophenolate and traditional immunosup­
pressive therapy needs further exploration.''"'' 3f the disease
is relatively inactive and the patient is asymptomatic or only
mildly symptomatic, low-close immunosuppression alone is
recommended to slow its progression. Acute exacerbations
may need periodic systemic steroids. These patients should
be monitored by baseline Goldmann visual fields and h&G
and yearly Goldmann visual fields and, less frequently, I:KG.
Antigen ЕИЛ-Л29 is found in approximately SWo of
patients with vitiliginous chorioretinilis.5£il'Sfl3" rK,!'' The
author believes ]ELA-,\29 is positive in lOO^b of cases.
If a patient suspected o f birdshot choroiditis is H I A
A-29-negative, diagnosis such as sarcoid or olher granu­
lomatous disease should be sought.''4, Vitiliginous cho­
!'. n4-;.:i:lh li.v- occurred in mt'iuv.y^Uic twins. ' Over
50^'d of patients may demonstrate evidence o f an in vitro
mitotic immune response to purified retinal S-antigen.' '
These findings suggest that this disease has a genetic pre­
disposition and that retinal antoimmunily plays a role in
its manifestations.
i 1,4b Vitiliginous chorioretinitis and choroidal and
retinal neovascularization
A —E: This healthy middle-aged man was ref-erred ir for
pusLbevacizLiritaEi fHtidopnlbltnills of Lh« lefl eye. He bad
received IWn l п Irav iltea I injsclinm» fur rutTvascular A M U in
Inis eye. Following a vitrectomy and lensfiEtotny, Ejoth eyes
Were nolud to have several drusen, and a partly aclive ju?i-
Lafoteal ЙгоЬЫсЩ nt’uvascular membrane wich subrelinal
hBJncxThage in Ihe let! eye. l-п add i I ion, several oval depjji]-
mentetl choroidal ies-:ans of b iredyhtrt сЕкпю геитИн iv w e
f(]uncJ jn lioLh еуед '^A and H, and E The druHen lit up early
in Ihe an^io^ram and stained ]ate, й1опд with lhe choroidal
neuvascular membrane fC and DJ. He continued lo receive
ranihi ^umalj and the vision stabilised nil 20/50 follcjwin^
secondary intraocular lens placement.
F and C : Irregular dilation a i retinal veins and retinal hfmor-
rhayos in [hit 5 1-yea r-ol d man who had only a few depiy-
munted patches in his left «ye w hen initially examined I'fc:.
Three year? I a lei he had developed pmminenl vililiginous
patches in both eyes ■.lJ.i.
H and I Thin 54-year-old w m ia n w ilh vitiii^inous cborioreti-
nilis developed loss of cenlraE Vision in both eyes because of
с hordi da I neuvascu lari sat ion.
J and K: This man w ilh vitHTgfttoM c h o r f f f f ilip b developed
relinal and Dpi it disc neovascularization that required pan-
relinal phtJlocoa^uiaLicm and vitrectomy.
l l ;u>:J I-, fro m C.J.L'ib ' " C) l M E , ■ Ч тг п с .п i ML-dk'.Ll Л # я к ы ! ю п . A ll n ;;Jiis
rLBCirV-LTd.J
'Lbe differential diagnosis before the development of
lhe typical hypopigmented fundus lesions includes pars
pfan ilis, idiopathic vitritis, reticulum cell sarcoma, papilli­
tis. and papilledema. Erregular dilation o f the retinal veins
and scattered retinal hemorrhages suggested a diagnosis
of macroglobuIinemia in one case. Several patients with
papilledema were thought initially lo have an intracranial
lutnor (Hgure 11.46G]. Once the typical hypopigmented
fundus lesions develop, the appearance and course o f this
disease differentiate it front other diseases that have while
spots in the fundus associated with vitreous inflammation,
such as serpiginous choroid ilis, АРМ PPL, diffuse unilat­
eral subacute neuroretinitis, sarcoidosis, Behcet's disease,
reticulum cell sarcoma, combined variable immunodefi­
ciency.''"^ and Whipple's disease.
Vililiginous chorioretinitis shares some features in com­
mon wEth the M C P [pseud о-ГО I iS] (see p. 98Б-990).
Unlike the latler syndrome, vililiginous chorioretinitis
rarely affects children and young adults; is infrequently
associated with anterior uveitis, punched-oul chorioretinal
scars, or choroidal neovascularization; and is associated
With ! LEA-A29.
The relationship of patients with vitiliginous chorioreti­
nitis and the more frequently encountered chronic viiritis
and macular edema more often in middle aged or older
women buL without evidence of lhe typical vitiliginous
lesions, is unknown (see p. ШЗД).
BLAU S Y N D R O M E
IJlau in 19R5 described a i^rge family whose members
were affected by a disease resembling infantile sarcoid­
osis,5^ Granulomatous inflammation o f three organs
resulting in uveitis. arlhrilis, and skin rash with an auto­
somal-dominant inheritance was noted. ihe symp-
Loms begEn early in childhood, wilh lhe s-kin rash being
observed as early as age 4 months Lhe ras-h is composed
o f painless tiny red dots and often resolves spontane­
ously. Occasionally more visible fiat-lopped papules and
ichlhyobis-like rash have been reported. u -"'" Somelimes
the rash can be so mild and may be missed. 'lhe joint
anomalies always appear before age 10. И begins insidi­
ously with painless cysts on the back o f lhe feel and Wrist
(figure M.48h) and mild boutonniere deformity of lhe
fingers, a characteristic finding in this condition (figure
11.4Й1-). The cysts over the joints progress to camplodac-
Lyly and cystic swelling of the wrists, ankles, knees, and
sometimes the elbows, 'ihe affected joint is mostly pain­
less and (he condition does not lead to severe handicap
until the fourth or fifth decade. However camplodactyly
may interfere with fine finger movements in early child­
hood. Narrowing of ю т е of the joint spaces and enlarge­
ment of metaphysis are rare."1'' ihe eye findings are the
mosl severe aspect of lhe syndrome. Jt can begin anywhere
in early childhood or in adulthood and could be an ante­
rior uveitis or panuveitis presenting with conjunctival ery­
thema, subepithelial corneal opacities, cells and flare in
the anterior chamber, and posterior synechiae. Recurrent
episodes result in calaraclr peripheral anterior synechiae
and second ary glaucoma. Progressive involvement of the
posterior segment wilh multifocal choroiditis (figure
11.4tiD and K], optic disc edema, cystoid macular edema,
vitreous membranes, anterior ischemic oplic neuropathy,
and an epiretinal membrane can occur.
The histopathological examination o f the skin shows
noncaseatittg granulomas in the dermis and multiple epi-
theliodalr multi nucleated giant cells similar to that seen
En sarcoidosis. However, on electron microscopy, comma-
shaped bodies are seen within the epithelioid cells- a
finding not found En sarcoidosis, which helps differenti­
ate pathologically IJlau syndrome from sarcoid. Synovial
biopsy reveals granulomatous inflammation xvith gianL
multi nucleated cells
labs el al in described an additional family with
disease resembling Klau syndrome with dominant inheri­
tance, granulomatous synovitis, and bilateral recurrent
uveitis. ]h is family had associated cranial neuropathies.
Including hearing loss and sixlh-nerye palsy without skin
M .47 Bird shot chorioretinopathy and retinal
n eovasc u la rizat io r .
A—G : This ^-уедг-оИ malt? presented with floaters Find vit­
reous hem ofrhaje in- hi-н ri|^hl eye. He had s'evitral areas of
flat neovascularization in [he righl eye in addilton to oval
рл Ее yellow t:bc)foid-ial lesions ali over I be fundus in bolh
eyes -А. and Dl. An confirmed Jhe a » a 5 of
neovascularization (Cl and El' and in addition revealed late
tynloid та « :и 1ч1 г edema in boHi eyes. H e received in tra^ rain
in jtd lo B fi ol bpyaciJCumab in this eys and w S storied on
immunosuppressives. The new vessels recessed oom plelely
(F and C)r He (hen developed new vessels, in his left eye that
also responded Co bevacizurmib.
Ю l u r ^ y £>f L)r. D a V id J.jr r .il . l
involvement. It is likely that the skin involvement was
mild and went unnoticed. '' Blau syndrome is differenti­
ated clinically from early-onsel or infantile sarcoidosis by
lack o f visceral involvement and familial occurrence, lhe
expressivity can be variable in family members with the
same mutation, lh e susceptibility locus for the ESlau syn­
drome is on chromosome 16 at l(ip]2 -l(jq 2l, in close
proximity lo the JnllanimatOiy bowel disease 1 (Ш Ш )
locus, and has been identified as the nucieotide-bind-
ing oligomerization domain 2 gene ( N 0 0 2 ] . 1-556 Л
cTmonLh-old infanl has been described with dissemi­
nated systemic granulomatosis, the triad o f uveitis, skin
rash, and arthritis, and gastrointestinal trad granulomas -
features of early -onset sarcoidosis, Blai4 syndrome and
Crohn's disease.'1' His family history was negative and he
carried a susceptibility polymorph ism of .\ГСЮ2 previously
described in Crohn's disease and nol in early-onsel infan­
tile sarcoidosis or Jilau syndrome.
TU BU L OI NT ER ST IT IA L NEPHRITIS
A N D UVEITIS S Y N D R O M E (TINU)
Dobrin et a I. first described this anterior uveitis associated
wilh acute interstitial nephritis and immune-mediated
process. A female pnedomEnance and bimodal age dis­
tribution, the first occurring between ti and 15 years and
the second beLween 30 and 35 years, have been noled,
aEthough (he disease can p resent from age 9 to 74. It lends
lo occur earlier in males, wilh a median age o f onset of ] 4
(range 9-52 years), and a median age of onset o f 17 years
(range front 9 to 74 years) in females.1^ Ш.А-Л2 and
liL'\-A24 are Lhe mosl commonly reported HLA types.
In Japan, about 754ii of patients were identified with
J EE.A-A24.
 Risk factors for development o f acute interstitial nephri­
tic are a wide variety oJ' drugs. predominantly anli infec­
tious agents, infections., toxins лtid autoimmune diseases.
Nro precipitating factor has been found in some patients.
It is not known whether patienls having an infection or
drug-induced renal disease are at an eqund risk of devel­
oping uveitis as patients with idiopathic renal nephritis.
About one-hatf of the palients have no reported risk fac­
tors for acute interstitial nephritis, antibiotic use was docu­
mented in 24% o f patients, and prior use o f nonsteroidal
anti-inflammatory drugs was reported in 1S°a of patients.
Some palients with TINLJ have been found Lo have sero­
logical evidence Ы autoan Li bodies such as anti nuclear
antibodyr rheumatoid factor. anti-DNA antibodies, anti-
cardlollpin antibodies, and cytoplasmic antineutrophil
cytoplasmic .antibodies, that is. c-ANCA. One patient pre­
sented with T IN U ;md Sjogren's syndrome. One patient
developed nodular scleritis 10 years prior to development
o f TIN IJ.1 There have been reports o f family members
wilh other autoimmune diseases, such as a patient's father
had VKH syndrome, and a sister who had ulcerative coli­
tis. Jherr have been monozygotic twins who developed
T IN l| approximately I year apart.' 1 A mother and son
With I1NU have been reported I here have been cases
of'i'INL] presetiling with uveoielinitis along with t-anconi's
anemia, and two sisters being affected in Japan.'"'1
The syslemic features associated wilh TIMLI are fever,
weight loss, fatigue, malaise, anorexia, weakness, abdomi­
nal flank pain, ihrthralgias, and myalgias. One patient
reported a red rash, likely drug-induced.
The ocular features are mostly acute, almost always
bilateral anterior uveitis (I'igure 11.4ftG). There has been
only 1 case with uitilateral interior uveitis. Patienls have
been described with relinal vasculitis, retinal hemorrhages,
optic disc edema, uveoretinilis []:igure ]].43>i), retinal
vascular sheathing, dilated relinal vessels, and Jipid exu­
dates. Pais plana exudates and cells in the anterior vitreous
have been noted, in some, this may be a spill-over from
the anterior uveitis.
A recurrence of the uveitis can be seen and it is quite
common, occurring in about 4 i% of patienls; the recur­
rences are usually more severe than the initial episode.'""
ihe recurrence is defined as development of ocular inflam­
mation after a period o f disease quiescence. Younger
palients less than 20 years of age are more likely to have
a chronic course of uveitis, with persistent inflamma­
tion lasting greater than 3 months, than older palients.
Intraocular complications include posterior synechiae,
optic disc edema, cystoid macular edema, macular pucker.
E1.4H Auto fluoresce nee in birdshot chorioretinopathy;
A and B: This OS-year-old woman with motieralelу advanced
birdshot chortdre4innpal№ had extensive dtval depjjgSented
les-ions fn bolh eye*; Ai. itim e of the leSicmS} showed Icres c l
overlying reLinal pi^m-t'nl epithelial ■'Rl-11j tells. The: areas of
FilJ E: loss- wtwe hyts&iulaJluoresceriL Several of lliese were
along the lar^e relinal veins, suj^esLinn prrtnary or sev:or>dary
n.’tinaf venous changes causing R l’fc atrophy in (heir vidnily.
lilau (iabs) syndrome,
C -F: Tins- 28-year-old Caucasian lemaJie w ilh a long hiu-
lory Dl arLhritis and uveitis, previously Created w ilh ste­
roids-, cyclospuiine, and moLhal rebate, complained ■ slow,
plftflreSsive decrease in vision- in the left eye. The arlhntis
involved joints- tn tin1 ri^hr hand with mild invokem enr ol
jainlh of the lull hand and wri-bL. H er fa Lhor, paternal jfefand-
falher, and brother had similar symptoms:; Her visual acuity
Was.-20/20 in her rijjht and 20/40 in the let). 5 he had 1 - cell
and flare in lbe dftht eye and 2+ ceil and flare in Ihe It’ll
eye. There were nongranulomatous old keratttic precipitates
on both comeat epiLhelia. The ri^hl fundus showed several
o ld chorioretinal scars in Lhe periphery (D and E) and lh e Tell
cysloid m acular edema. Examination of Ih e hand showed
a typical boutonniere deformiLy ol the index linger and lhe
Eillle finger on both sides (Ft. H e r diagnosis is consistent w ith
familial juvenile systemtt granulomatosis, also known as labs
syndrome or tilau syndrome.
Tubnlointerslitial nephritis with uveitis I.T IM J),
C —|: A 12-vear-old Caucasian girl was seen for red eyes and
decreased vision. rifjht more than left. l-E<-r vision was 20/Ati
on lhe rijjhl Hind 20/20 ort lhe left. hongrnmulomalous anle-
: iOr uveiLis wiLh keratic pre( ipitales Gl and -tleep puncfeifcd-
out scars (H i w ere seen in the inferior retina. There was a
prior hiuloiy ol low-^rade fever and weight loss. B lo td urea
nilm^en was 2 5 m ^ d l, crealinine was 2.4f and urine exam ­
ination E-howed 10 whiluj blood celln pier hijjh-power field,
red btood ceils, and hyaline casts, p- and c-ANGA and anti-
glomerular basftj^neni membrane 1GBM) a nLiiiadies wr^re
negative. Kidney biopsy showed no granulomas, but mixed
inflammalorv infiltrate I and Jj conMslenl w ilh IIN L -.
I t J —1-. r j u u r l L j i y o f U t. l i m o l h y U l i c n ; C j —J , c c K j r l c s ' y с Г U r . l o s « M u lic t u .)
chorioretinal scar formation, and ] patient wilh a rbeg-
malogenous retiiial detachmenl. tilevated intraocular
pressure can he second ary to the uveitis and synechiae.
Secondary cataracts bolh from the uveitis and with cortico­
steroid use in the treatment are also seen. Visual acuity as
good as 120/25 or better is seen in both eyes in Lhe majority
of patients if treated promptly with topical and systemic
sleroids.
 ]Ъе pathology of the disease is not completely under­
stood; it is believed to be autoimmune. The rena] iJLag-
nosis is established by a kidney biopsy, which shows
interstitial edema and infiltration by inflammatory cells
of the kidney (figure П.4Ы and J]. The glomerular vascu-
Ear structures were relatively unaffected. The inflammatory
infiltrate in the kidneys is composed o f mononuclear cells,
including lymphocytes, plasma ceils. histiocytes, some­
times mast celts, eosinophils and neuLrophils. Llevated
serum beta-2 microglobulin is seen in more than 6 0 % o f
patients and urinary beta-2 niicrogiobulin is seen in more
than 50^-L) o f patients; this is a marker for the presence
of the disease and the disease activity. Non renal findings
have been occasionally described in the gastrointestinal
tract, bladder, and lymph nodes, Laboratory investiga­
tions include urinalysis with Itm'-grade proteinuria, gly­
cosuria, urinary leukocytes, and beta-2 microglobulin
levels, Eilevated sedimentation rate is seen in majority o f
patients. The serum ]gC3 is also elevated in about 80°o of
patients; anemia is a common finding. Treatment involves
the use оГ systemic and topical steroids along with cyclo-
plegic agenLs and any pressure-lowering agents if needed.
Immunosuppressive drugs are reserved for refractory uve­
itis or multiple recurrences. Uveitis sometimes predates
the interstitial nephritis, but most often the interstitial
nephritis is the first presenting feature with flank pain,
fever, nausea, malaise and other findings The T lympho­
cytes appear to be activated, as evidenced by inter leukin-2
receptors on the cell surface.0"'^
The diagnostic criteria for the acute interstitial nephritis
include histopathological findings consistent with the clas­
sic interstitial nephritis on renal biopsy. Clinical diagnosis
is based on abnormal renal function and abnormal urinal­
ysis and a systemic illness lasting more lhan 2 weeks char­
acterized by fever, weight loss, anorexia, malaise, fatigue,
rash, abdominal flank pain, arthralgias and myalgias and
a sedimentation rate above 40 mm tig, evidence of anemia,
abnormal liver function, and eosinophilia.60'' lhe diagnos­
tic criteria for uveitis include bilateral anterior uveitis with
or without intermediate or posterior uveitis. Onset of uve­
itis is less lhan 2 months before, or less than 12 months
after, acute interstitial nephritis. Unilateral uveitis is rare.
In Japan, 50% of children with uveitis seemed to have
TLNU; the other 504h sarcoid in several series.1,1'1'"1
C R O H N ' S DISEASE___________________
Crohn's disease (regional ileitis) is a granulomatous
enterocolitis of un known etiology that usually affects
young adults. Approximately 10% of palienLs develop
ocular complications/'10 Ihese include corneal infiltrates,
conjunctivitis, corneal ulceration, episcleritis, scleritis,
choroidal folds, acute anterior nongranulomatous and.
Less often, chronic posterior granulomatous uveitis, acule
iritis, macular edema, central serous chorioretinopa­
thy, proptosis, papilledema, retinal vasculitis, and neu-
roretinitis.lisLl_'1Jlft Gass has seen 1 patient with Crohn's
( 1.49 Immunoglobulin A (IgA) nephropathy.
A -L: A 21-year-old wum an complained o f abdominal pain,
w m itin g and shortness of breath associated w ilh visual blur­
ring lor 1-2 days. There w efe several purpuric rashes all over
her body 1121 rind she wan known lo h ate end-btoj^e rcmal dis­
ease requiring herrtodlfifysiii she wan found Lo be anemic wilh
an elevated potassium, blood urea nitra^en^ and creatinine.
Vision was count finders on Lhe right and 20/30 on Lhe left.
Exudative relinal detachment of lhe ri^hl eye and choroidal
thickening ol lhe left were зеел IA-C). F’inpoinl hvpertluoreH-
cent dots Lhal leaked progressively w ere noted on an^iof^raphy
([J-Gf. An ultrasound 1HJ And optical coherence fnmogiaphy
If.Jf.l: confirmed Lhe s uiinel i Па I fiuid. ltiu CX.'Г showed muJ-
tiloculaled fluid due Jo HufweLirwi fibrin stands -1 1 1 . She was
known lo havfj biopsy-proven I^A nephropathy. Aggress iye
pentoneal dialysis f[]l|i|^ed by h eniodi а 1ун ii, correcLi on of
her araefnla and conLrol of blocxl pressure improved her ocu­
lar slatus vviLh visual Telurn Lo 2ЕУ20 in holh eyes. The serous
detach menl resolved and Li]schni^ tpotsi and a few retinal
hemorrhages remflined t|—L.I.
i iliг1.1 sy o f L)r. knirij!I D h jtiw fl] arid Dr. L j k J,,m ,L O t T iiL 'd iu k ..
disease associated with erythema nodosum and typical
АРМ IT E:.0,1' Others have reported multifocal choroidal
infiltrates similar to АРМ PPL! bul associated with serous
retina] detachment in Crohn's disease.1^ Systemic mani­
festations include low-grade fever, abdominal pain, diar­
rhea, anemia, weight loss, arthritis, psoriasis, erythema
nodosum, and hepatitis. Ocular complications are more
likely to occur during the active phase o f the disease, and
at least 50% (.if these patienls will have evidence of arthri­
tis.'1' ' Tallents with colitis and ileocolitis are more
likely to have ocular involvement than patients with only
smaJI-bowcl involvement.14' There is a higher than normal
prevalence of EII.A-B27-(ype leukocytes in patients With
Crohn's disease.^'' CAfljDi5 /N OD2 mutations haw been
implicated in lhe causation o f an autosomal-dominant
inherited disease, called Jilau syndrome (see above). Ihe
gene CARD 15. also called N0112, has also been implicated
in other granulomatous diseases, including Crohn's dis­
ease, and in early-onsel sarcoidosis. ,\'OJ.l2 normally con­
trols both innate and adaptive immune responses through
the regulation of cytokines chemokines, and antimicro­
bial peplide production/'" Strong evidence suggests an
initiating and promoting effect o f intestinal microbes in
the gastrointestinal tract of NOD3-predisposed individu­
als. lhis could be the underlying mechanism for patho­
genesis o f Crohn's disease in the susceptible individual.
C O L L A G E N V A S C U L A R DISEASES
Throughout this textbook, various ocular manifestations
of collagen vascular diseases have been illustrated relevant
to the context, given the protean manifestations of some
of them. IgA nephropathy, systemic lupus erythematosus,
and Churg-Strauss syndrome are illustrated in figures
11.49-11.5].
]gA Nephropathy
Palie nls present wilh malignant hype rtension, Ruid reten­
tion, and generalized anasarca.1 ^ Kidney biopsy shows
IgA nephropathy wilh focal and segmental mesangio-
pjthle changes and immunoreaclivily to IgA with depos­
its of [gA in tlie mesangium. tiolh circulating immune
completes and in situ production o f immune complexes
wilh complement activation are involved in the pathogen­
e sis.^ Hgures 11,45 and 13.50A-E illustrate two women,
one of whom (E'igure 11.50) also suffered abruption of her
placenta wilh a stillborn child and subsequent mild dis­
seminated inlravascular coagulation; she presented with
hyperLensive choroidopathy, retinopathy and exudative
retinal detachments. Jhe women responded lo combined
treatment with antihypertensives, systemic steroids and
immunosuppression., with complete resolution o f retina!
findings.
Systemic Lupus Erythematosus
figure 11.50F-H illustrates a patient who developed bilat­
eral exudative lelinaE and choroidal detachments (figure
Ll.&OfJ with second ary angle closure glaucoma due Lo
forward displacement o f the lens iris diaphragm. Renal
biopsy helped make [he diagnosis o f lupus neph гора thy.
Treatment with systemic steroids alone did not help; addi­
tion o f azathioprine caused resolution. She Eater devel­
oped spontaneous peripheral vascular occlusion in her left
eye wilh Vascular remodeling (figure 1] .5ОС and H).
Ocular manifesto lions of hi pus include isolated cotton
wool spots, relinal vasculitis wilh or without subsequent
non perfusion, furLscher like retinopathy (see chapter 6),
serous retinal detachment resembling VKH disease and
secondary hypertensive retinopathy.
I 1.51' Im m u n o g lo b u lin A (Ig A ) n e p h ro p a th y and
ecla m p sia ,
A-E: A 2E-year-oid Indonesian wom an complained ul"binned
vision ir both eyes. Visual acuily was 20Л1М in each eye w ilh
a small myopic refractive error. Anterior-segjnenl examina-
tlon wan пС5ГМ |ЛI. Dilated fundus HKrimiitatitm showed detach­
ments of lhe macuIs with subndinal fibrin larrctw A and Bi and
several yellow iesions al lhe level of the pijjBftnl L;p>iIltr>Iium
in Isoth eyes. I here were bilaleral exlens ive inferior exuda­
tive relinal delachmenls (A. ]1, D, and E). Fluorescein angto-
showed pinpoint KypertljorescertCiB conespundinq lo
the yellow lesions lhat leaked in lhe mid and late frames of
lhe- ■11'li .■';^i'u "i i::i u:lk'< lion <H d'-c- n Ihe sut^oNi:..: -p.k'c-
It.!I. Optical coherence lomoj^raphv shm v&j serous detach­
ment w ilh fibrinous strands in bolh eyes. FLve weeks previ­
ously, lhe patient had Ijeen admitted few a ruptured placenta
and had delivered a stillborn baby at 22 weeks' gestaliun.
She was diagn<rced with elevaLed blood pressure, proteinuria,
a rd elevated creatinine at 19 weeks' gestational age. Her
blood press ure was up to P7ty I 11 mmHo, She had 3 + pt’dal
edema, a weight gain o f 14 lb (6kg) in 2 weeks, and a creati­
nine Lhal went up Lo 2.7 from 1.7. A renal biopsy confirmed
ГцА nephropathy w ilh rapidlv progressive nephritis, and no
findings su^geslive of pr-e-eclam^a. Th]s patienL devsloppd
fuyperlensive c^raf^dopatity ahd i^A nephropathy-ajg^fciated
chorokkfpalhy with exudative retinal delachn'ittnl. Her clini-
саГ course was also complicated by anemia and disseminated
intravascular coagulation. She was treated with oral predni­
sone al {lOmg^day, azalhioprine 100 m|ydav, :^nd .mlibioLics
Luvotloxaci n and BacLrim along w ilh aniihypertensives. Her
Visual acuily improved over lhe next 2 monlhs Lo 20-f60 on
Lhe righl hind 20/40 on lhe lefl w ilk resoluLion of the exuda­
tive retinal delachmenl leaving behind pigmentary changes of
chronic flscbnijfS spols.
Syslemic lupus erythematosus and vascuEopalhy,
F-H: This 24-year-old W4jman wiLh native Am erican, African
American, and Caucasian ancesLry recently diagnosed w ith
lupus nephropathy develofied sudden loss of vision in bolh
evtfs secondary Lo bilateral choroidal etV-u-sions anti exuda­
tive retinal detachm cnls 'A ). Her intraocular pressures were
elevaled due to forward movement of lhe iri-ь lens diaphragm
from the ciliary detachments. Treatment w ilh oral steroids
alone did noL help, bul her findings № scl№ d once azalhio-
prine was addl'd. Her vision and fundus changes returned
Lo normal in 2 months, "three years later -she was seen lo
develop asymptomatic peripheral vasculopathy in the left
eye w ilh retinal hemorrhages and vascular occlusions itJ.
a n o w ,ind Hi. I hat evenluidly stabilized in 1 year wiLhoul
specific LreaLment. She was on svsLemic IrealmenL for Lhe
lupus HhrougbaUt-
CtfJJrKyi-r ^ faiiariir rWprtirftfs 105]
Churg-Slrauss Syndrome
(]hui£-Slrauss syndrome is an allergic disease cha rat­
ter Lzed by eosinophilic granulomatous inflammation
affecling the respiratory tract and Ltecrolizing vasculitis
involving lhe small and medium-sized vessels. Four of
six criteria, which include asthma.. hypereosinophilia..
mouoneuropathy or polyneuropathy, paranasal sinus
ab norm aLily pulmonary inlillrales (I'igure 11. BIG ), and
exlravascular eosinophilic infiltration (Figure 11.51 E),
should be met to establish the diagnosis. ']Ъе heart, skin
(bigure 11.51H), and gastrointestinal iract can be involved
occasionally. Ocular involvement is very rare and includes
conjunctival granuloma, uveitis... corneal ulceration, amau­
rosis fugax, ischemic optic neuropalhy branch and cenlral
retinal arlery and vein occlusioitr and orbital pseudolu-
mbk617-640 The palienl illustrated in I'igure 11.51 shows
progressive surgically induced necrotizing scleritis (51 NS*
see also page 1020) and retinal hemorrhages and vascu­
litis. He had skin involvement wilh necrotizing vascu-
Lilis. pulmonary infiltrates, biopsy-proven eosinophilic
inflammation, and extensive relinal vasculilis, fulfilling
the criteria for the diagnosis of Chu^g-Strauss syndrome.
Treatment involves high-dose intravenous and/or oral ste­
roids, immunosuppressives such as cyclophosphamide,
and supportive therapy wilh platelets.1'4
И .j 1 Churg-5Irauss syndrome and s l i rgically induced
necrotizing scleritis.
A-l: A j iJ-y еаг-otd Asian physician underwent esLracapsular
LataracE surgery in his left eye in 1994. Л year later glaucoma
was diagnosed and Xalalan eye A n p s Was liSjgUn. bioven
yediS later his to rhea I wound lie^jn Lo melt with movomenl
of the iris lo wtTund and disJocalion of the [josteriar-cihamber
intraoculaj lens. The corneal mell was covered hy conjunc-
Liwjplasty. His vision declined Lo Э/200. Five months later his
intraocular lens was exchanged fur an anLerior-tihamher lens
via a pare plana vilroctornv. (Jhrxmic red eye and eye pain
persisted, \A) and was treated with bi^h-dose ibuproten and
Lopical prednisone acelate i'cu Ihe next ireveral monlhfe He
also developed a chunoidaJ neovascjular meftibrane in his lefl
L^e requiring ranihi^umah injciclions -IS and O . O ver lhe nexl
monlh he developed progressive thinning and necrotic scferi-
Lis ел Lending irom lhe limbal wtMjnd consislenL ivfth surgically
indiiced necrotizir^g sderiLis ID and Ef. A chest X-ray revealed
right middle Hind lelL upper-lobe opacification (G;-, increased
blend Urea nilro^en .liTd eosinophilia ■I 5'^mJ. He fulfilled the
American Rheumatol о д а ® g o cim ft orL-eria for Chur^-itrauss
syndrome w ilh aslhma, paranasal sinus abnormality, hype-
neosinophdlja, and pulmonary infiltrates. Syslemic fin din g
included retinal vasculilis IH'l, skin papules ;FJ, and eoe-inn-
phjlic vasculilis It).
I 'J u L i r C t i V (>| pF3. f . M ir h a d 1II".■| 4 T. k l l l x ' l 1 'i V i Iг : hi. k k ll.'.N I
M cL Ju n .iJd , iinrE t nuric:ll 1 <"■11 ir: nvl i.lii:-. I
i&allagcti Оё"(ияэйе Ю 53
FAMILIAL C H R O N I C
G R A N U L O M A T O U S DISEASE OF
CHILDHOOD
Chronic granulomatous disease o f childhood is a geneti­
cally determined disorder characterized by relentless suc­
cession o f chronic granulomatous acid suppurative lesions
o f anany organs caused by a defect in the ability o f the leu­
kocytes Lo kill certain microorganisms after phagocytosis.
'lhe disease affects primarily young maEes, manifests
in infancy, and frequently results ln death in early child­
hood.1 ': Young male palients present wilh chorio­
retinal lesions or scars associated with recurrenl systemic
infections such as pneumonia, suppurative abscesses of
various organs and osteomyelitis. ETtese lesions are usually
picked up on dilated retinal examinations performed on
hospitalized children in the ECU. ihe active lesions appear
yellow gray and the inactive are pigmented punched out
scars varying in size from 500 microns to taige confluent
lesions/'"1'1_‘"1' lhe more often seen inactive lesions some­
times resemble the lacunae described in female patienls
wilh Aicardi's syndrome. I hey are frequently presenL in the
peripapillary area, and lend lo follow the distribution o f
the retinal vessels oul toward lhe periphery, often sparing
Lhe macular region (figure 11.52 A-D). Optic atrophy may
he presenl. Occasionally patients present wiLh significant
vitritis and suppuration, often, vitreous biopsy does not
yield an organism. Women are X linked carriers and are
usually asymptomatic. J lowevcr. some women may mani­
fest some o f the systemic features o f the disease and have
deep chorioretinal scars usually distributed along blood
vessels. 'Ihe scars resemble those seen in multifocal choroi­
ditis [figure 11.52 C-}:).
Chronic granulomatous disease is an inherited im m une
deficiency disorder of the neutrophil \AD EJii oxidase
complex featured by its inability to produce reactant super
oxide and its metabolites such as hydrogen peroxide,
hydroxy! anion and hypohalous acid, 'lhe neutrophils are
able to phagocytose microbes, bul are unable to generate
superoxide and hydrogen peroxide that is needed lo kill
the m icrobe.'1* 9lence these patients suffer from recurrent
and chronic bacterial and fungal infection in the form of
pneumonia, lymphadenitis, eczemaloJd dermatitis, osteo­
myelitis, hepalosplenomegaly and abscesses from sapro­
phytic organisms.
There are 2 patterns of inheritance: the more common
X linked recessive in 70-30 % and the less common auto­
somal recessive inheritance in 20-30% of patients. W ithin
each mode of inheritance there are 2 separate generic
types - cytochrome b55S negative CGE} and b55S positive
CGD. The X- linked cyLochrome b55S-negaltve C C D com­
prises 60% o f cases. Autosomal recessive СС1Э is milder
and may present only in adolescence.
Phagocytosis initiates a biochemical chain reaction
called respiratory burst in neutrophils resulting in a vari­
ety of microbicidal reduced oxygen metabolites such as
superoxide and hydrogen peroxide. Neutrophils in CGD
И ,d 2 Carrier slate of chronic granulomafous disease
A -F: This 2.1 vear old woman carried a diagnosis al" 'Crohri's
disease' Гог 10 ytjars. Shy was found to have [he lesions in
the kmdus un ап examination Гог fkilters lhal she noted
whenever '.lie Crohn's disease flared up. the.1 had failed
multiple therapies Гог Crohn's including methotrexate, mer-
daptopurine; hum i ra, femicade and was currently on 40 mg
tirep™i)nB/day. Her vision was 20/25 in each eye, lhe
anterior ье^гпеп! and vitreous were quiet. There wert! suv-
eral found chorioretinal scare, many along blood vessels
in bolh eyes., with peripapjillary scar in lhe ri^hl eve (A-[)l.
FIuortwcei n an^iojjiam rm/ealed staining of Ihe <.hronic
Eesions 1E and F). Her Uncle died of chronic granulomatous
disease as a child, an a uni carried a diagnosis; of 'ulcerative
colitis' and was found lo he a carrier of C C D and hvo o f her
grandmother's brothers died ot ССЛЗ us children. The palir'nl
was also torrid lo be a carrier of CCt>.
C t iu r le b - y . D r . S l w L ' n B r r t t t t L l
lack the respiratory burst and thereby cannot kill certain
bacteria, Ilowever organisms that themselves produce
hydrogen peroxide such as Streptococcus groups В and D.
Streptococcus pneumonia, and Clostridium difficile are
billed by C G D neutrophils. Catalase positive organisms
such as Staphylococcus aureus, pseudomonas, Candida.
Aspergillus, t. colt remain viable after phagocytosis by
CGE3 neutrophils.
Aspergillus is the commonest organism causing dissem­
inated pulmonary infection, which is lhe leading cause of
death in ihese patients. Staphylococcus aureus liver infec­
tions are next most common. JJecurrenl skin abscesses,
perianal abscessr osteomyelitis are frequent. Some palients
develop strictures or obstruction from granuloma in the
esophagus, gastric antrum and genitourinary trad. Women
carriers can develop a milder form o f lhe disease and
often suffer from enterocoliLis that es often misdiagnosed
as Crohn's disease.1"1'1'Ihey have a dual population of cir­
culating neutrophils based on random X-cbromosome
inactivationflyonizalion). Recurrent antigenic stimulation
leading to autoantibody formation may explain the appar­
ently increased frequency o f discoid lupus in female carri­
ers o f
lxmg-term prophylaxis wilh antimicrobials with trini-
eLhoprim and sulfamethoxazole, itraconazole and gam ma­
in terferon has positively modified the course of CGE? and
improved the dura ti oil лт1 цил!Иу of I Me Iriim ’lhi'prii'i-
sulfamelhoxazole has reduced the rate of severe infections
by 50%, interferon gamma (generates ] E-.O^} by 70% and
itraconazole has reduced Aspergillus infection by 50%.
Granulocyle transfusions can be used in life threatening
infections.’0- Active multifocal choroidal lesions that dis­
appeared after syslemic Lreatmenl with vincristine, pred­
nisone, and cyclophosphamide have been observed.',4-'
Jl is believed that the H3Q^ generated by ihe normal
neutrophils can diffuse Into defective CCL> neutrophils
and produce hypohalous acid and hydroxy] anion thus
killing the microbes. Granulocyte transfusions are gen­
erally well tolerated, bul adverse effects include fevers.
p u lm o n a ry le u k o s ta s is a n d d e v e lo p m e n t o f 1eu ко-л££| Li-
tin i n s th a t le a d to ra p id lo s s o f tra n s fu s e d n e u tro p h ils .
i\ ilm o n a iy le n k o s tris is is c o m m o n if A m p h o te r ic in a n d
g ra n u lo c y te tra n s fu s io n s a re g iv e n a l th e s a m e tim e h e n c e
s h o u ld h e a d m in is te re d s e v e ra l h o u rs a p a rt.
C C D re su lts fro m m u ta tio n s in g e n e s c o d in g gp91
p h o .v p 2 2 pho>t, p 4 7 p hox., o r p G 7 p h o x . X lin k e d C C D
re su lts fro m d e fe c ts in g p 9 ] p h o x a n d th e re m a in in g m u ta ­
tio n s re s u lt in a u to s o m a l re c e s s iv e C C D .
L a b o ra to ry tests lo d e le c t C]CL> reEy o n d e m o n s tr a tio n
o f d e fe c tiv e N A D p t [ o x id a s e fu n c tio n . I h e n ilr o h lu e telra-
z o liu m test d e p e n d s o n th e c a p a b ilit y o f n o n n a J n e u tro ­
p h ils Lo re d u c e lh e c o lo rle s s N J1 T d y e lo b lu e f o r m a lin
d u rin g p h a g o c y to s is., w h ile in C C D Lh is is n o t p o s s ib le
a n d h e n c e a n e g a tiv e Lest is d ia g n o s tic .
'i'ra n s d u c tio n o f b o n e m a rro w a n d p e rip h e ra l b lo o d
s te m - ce l! p ro g e n ito rs w ith c o rre c te d g e n e u s in g le L ro v i­
ra l v e c to rs has s h o w n im p ro v e d jS ifA D P H o x id a s e a c t iv ­
ity . S te m c e ll g e n e th e ra p y in a n im a l m o d e ls h as s h o w n
in c re a s e d re s is ta n c e lo e x p e rim e n ta l in fe c tio n .^ ''''
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43. MeGu nnssi R Mhchai P А сазе з1ifjte pKlE'icf null fral flaeod agmat ealhsicf ah,1
3iaaa:-a ndie^Lieira xte y\ ^ust J ^lldntoi Is77.j4^-Ei
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гг[кгзпе к ш т с h te same pa! enl;. feth CipnfalxJ l93E:l £7.' 89-91.
34&. СачроОДГix a lF J.Тгаьгтю;maniardkopti^Os.laTie 11££622-:.
246. Gi I e; Г.!. Sira J. Itnlq) 2 s al. Тгашэп: recm^dltr;-isenWiig acule in a la
reu'aieinapfllh; AustliZ JOalttiahiDi 1997:2E:£A7-1 J.
247. CQGbain' MH fell cl «р -кат agi *d caling i sral ielral inlact AmJ-OpTtfalnol
1973:2E.4Er-35.
246. Belial У fl, lJst:i H hti^ETii S. el a. '.tgl-tonirag -Hiada'a diease in Егсл, .cn..
ty(rttdmd19e&3£3*W.
249. Ben:..Ftraier-U.Lea'Js.elitoriatkiEл d hcalfieatJEsd liUogt-Ki^ffiagHtiada
^пТате. ^sI hd 1991:1 1:276-93.
260. Iba'e; rt. frato № MaettlhTAelal Мате!с театалн hagiiQ Indus m'Jojl-
Kopiici-tteraaa s^ndrane. lei na 19941 я.' 64-3.
2E'. Сипз S C'cr CH tim jjSJ.etal '.^H^'^i-haradscrpcT'ai e.hriJ
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252 P s r H i Ftrnl Fl.. Cfcnta aid hiODpoirtitec c b ^ a \m h sewre UcgHfa)(afHgi-££rada
sfn ix t. AmJ OTTajtioi 197: ;33:24£^э4
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266 Тгй™ V. S jci^rs S. vdf:j'a H el ai The asocial иг ber.ieer [гад hвЬсопрйЫ iU'
arfrgera ‘r iA and'it^l-h'^ag^aiaaa sinfrane. OjTuli>]i Jan
197&:30:qe6-9C.
26r. -. RiH H cm tElii^Esrfoasdic Irenes meadh rcgetf ffcmaa'ES- >ioi'e.
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269. Manner №.ijopesF^SfenMq J' F. elal s^icme п рлекз1. fri
Ctns-^se aTCSGlr;. AmJ Otfta nc 199^.114#' 6-?D.
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NI-. j£A J OtfilldtTfl 1Ж £ Ж 2 . '
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264. KmndSakaH.-DkjbeH fia^didtwanterDftfiambef as гй ^ п Д О т hHarada^
?flasne. A 'J. OpKral'vcl 1931 :ЁЙ:' 6 0 ^ .
266. Sirala S. Ha/arfi K, UasLca <.Йеле anje clcare gtiLaima is an rn al s gn i H i aca's
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sipndraTf. A-d--OpKTslricI l99£-:l C& 421 -&.
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hiaca sdaeaa fa J 1Ё7№ £нй.
2E'. JsTscfi CA, Te letsjm C£. Magnaic ге^татсе jr»ng nVonHtoraHfli-ttiatla fflrsicms.
Ami Ci:hiislnicn3!tti-.Ce 733-4.
270. R iB a i'e iIt, G a; JGM. ^Лл-Кщывд-Наай ^ т т е ! с n d c&jtm . teiapr. aid la^-
h i "i 'Jisui: outoms ^jc i GftilldTnci 1 ^ ' 632-r.
27' . Sain'alci t. '^na 3. f/alscdi H. Sioes у . я п е с е н с й Ше'азу n UogHGnonagi-ftoda
tiieise. O Jj-^rc^gti l993:2C-1:l62-7.
272. Sim a R Za'^n pla^lacge лйТтегаре - am liiJeii ftaWieit >ach ^Vilpania
Geil56ci69:2^E-7.
27i W 1ат P fyrpatietlc O'Tf a (rC s s тЬйтс Haaa's ciseae. J OpitalKil 1932:
274. Ch.rg V-M. №h 1-S. Lrear :trea^. lei c t r Te Iutcus eqJiler asscdaleo witi '/вдИлуящ--
Haraca ^rcrame fa J С стгиЫ 1ЙЖ.' Ю 745-ё.
270. Citscr ftF: Ke'maiB'.l Hetrtiragc 4 a;JaFdeo]d'n:ei(! n ihe^t-K'^Mnici-Hajiada
n Ja t . AmJ 0](-Тла :о^' 97: :Я:Ё32-6.
270 №olh,- FS. Crcra LF. Ff. -e: al Sctrelra г&мзеоя1ire ю - те г ,.'it-K'^‘iftici-
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K'Mniti-Haraca n-aате. A^- OpKfaiTcJ 1990:1 СЁ9' 0-9.
276. "ittara hr ^e-amsla; a E iK iisd vd‘ ,™ :jgt-+jc^nagi-HsiadiiffT>l'Tie.^: J OTtraiia
19Щ:1С6:69^-5.
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231 SsramtD 1 M uili Т. пакта H Class I n a or hGla:aifalb i^ smp e? ai netnK^si al
VogHmpnaflh^firada ciseasf. Atf. Cpid-aiicl 1991 :l №.' 270-4.
£32 Ctiar С-i. a!tn:h(j tso.vsn an'piTeiic ^thainic. Tsxa"fifty aendDfhlhiJai lii,
ггл 'Лд1-Кл?гачцц—am li dic-еам. CfhlldmDixv 1933:£&:&' 9-24
233 namita К Ea-anoso T. lmmT<nr£ctfem E J aLdiet cl 'ЛдНК^аидма^И disease лтг
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с Fjrpanetn cpTffai'ilsindlhe'wL-Kc^nici-Harsdas^Jr-a^. 5r'J C^lhiima
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306 jdJy B£lL. S ia t J. S^iipatttaic oprhal' sa m 2ana:a. Car J ^Itdm ai 1972 ,■157-Й.
^37 \laii J4 № r«ft f4 ^Tt parelic irNfiie iier cia l tea east feia a l £69 9 122-E.
308 M ^ JfR O T A a n r a m e fc n ^ ln a itaig-iefmfidBfi-iiMlCchlhamDi
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309 Maicc CLFajjff!;E.C[anjamalGii;aNSb;a;ij;'eGtn eircTaLlia,ada irsa'tfl'a -.:in
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316 fiass JDM $кгежорс;1азоггт1а -iieKsc: d a jc ® axtrealmei'L 2nd eo. ^l.LO'js
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licies. Qjttiairafcflv 196633399-6.
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329. FaohA JfuS.FoTFf. fynpalBfic (щ Ь й щ an tirnmjteftchanlri s w u f еаийнс
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Tumors o f the Retinal Pigment Epithelium (RPE)
Thfe terms "hamaitoEiia,' \btfrisloffia,г "phacoma (mother
spot}," .1lilI 'nevus" are used lo describe benign devel­
op menial tumors or placoid Lesions. Hlaiman's M editiil
Dictionary defines a hamartoma as: “a focal mal for malic n
thл1 resembles a пеорЗазф grossly and eVeti mtoos comi­
cally, bLit results from faulty development In an organ: il
is composed o f an abnoitnil mixture of tissue elements-
or an abnormal proportion of a sing]e element, normally
presen I al that site, which develop* and grows at virtually
the same rale as norma! components, and is not likely to
result in compression o f the adjacent tissue (in contrast
to neoplastic tissue).” A cboristoma is defined as a "mass
formed by maldevelopment of tissue of a lype nol nor­
mally found M that site/ Thacoma is defined as ла ham­
t J.O i Congenital hypertrophy of the retinal pigment
epithelium (CHRPE).
A: .Multiply areas of {JHFiF’fc simulatm^ lar^e animal tracks.
E and : Litres area of С.ГЬ-dhtl-11 mistaken fur a maliunant
melanoma ir а 59-year-old wom an w h o was asymptomatic.
Note нсгега! areas o f thinning o f lbe Kl'fc w ilbin IEh; central
portion c f Lhe lesion (arrows, JJ). There was- a r absolute field
defect corresponding w ith the tesion. Angjagraphv repeated
obstruction ol the background choroidal fluorescence except
in lhe areas o f Thinning of the RFC (arrow, O-
D: A jet black O I K P l w ilh small fenestrations larrow and
absolute scotoma in the param acular rw io n of a younjj
woman.
E: C H K P E a s s o c ia te d w ith m u ltip le fe n estra tio n s A r r o w s ) a n d
a p e rip h e ra l nUffiiffiffitibd rinH-

artoma found in phacomatosis/ a group Orf hereditary E: d W R P E sht^w in g g en era I ii e d iT yp o p i^ m en tatio n a n d a

diseases characterized by hamartomas o f multiple tissues.
A nevus is a "birthmark; a circumscribed malformation
o f the skin, especiatly if colored by hyperpigmentation or
increased vascularity; il may be predominantly epidermal,
adnexalr melanocytic, vascular or mesodermal, or a local­
non p ig m e n te d ptii i p h e ra l rin^.
C : O I K F ' t s h o w in g g j^ te ra liz e d luvpopi fom entation lhal
ex ten d s o u t It) a n d in c lu d e s a p o o rly d e fin e d , n o n pi fomented
rin ^ a n d a w till- d e iin e d , p ig m e n te d rin^.
H ;ind t: G r o w th o f С Н Й Р Е in a 47-year-old w o m a n h e lw e e n
la n u a ry 1Ъ 7 3 (H ) a n d Ju n e 19Й!) ill.

ised overgrowth o f me! an in-form mg cells arising in the | - L : G ro w th ol C H R F 't in to lhe c e n tra l m at u la r area o f the
left eye.
skin early in life.' Ophthalmologist*. have adopted the term
'fneviu Lo refer to developmental melanocytic lesions of [A-О Iftiitt {J.ftb1-. I: jrnJ I- frunt buL'ICriLiil-L. c-ULirCt'w (if Ur. НчИ.гМ
Dreynir. I
Lbe uveal iracl. and il has been suggested as an appropri­
ate term lo describe developmental placoid lesions of (he
R F E .1 nevelopmenlal uveal melanocytic nevi haw been depigmented lacunae xvilhin these lesions are frequently
described in Chapter 14. evident, particular]}1 in older patients {figures J2.0JU, D,
11 is important to realize that reactive proliferation ofli, and ], and 12.03C and H). Ihese lacunae may show
RPh, retina] gjial cellsr and retinal vascular endothelial progressive enlargement, and eventually the entire lesion
cells can occasionally duplicate the clinical and histopath­ may become depigmented (Tigure 12.01G). Although
ologic changes of all of lhe ttPE hamartomatous lesions most o f these lesions remain rather station ary. concentric
discussed in this chapter. enlargement lias been demonstrated in up to 74-33%
of cases (figure 12.01 El and I ] / " ’*1'1 Occasionally, lin­
ear depigmented streaks and localized zones of mild
M E L A N O T I C NEV! OF THE RETINAL hype rpigmen tat ion occur al the anterior margin o f these
P I G M E N T EPITHELIUM______________ lesions.' Uncommonly, nodular growth may develop
within CElEiPK1' with histological confirmation o f malig­
Solitary-Type Congenital Hypertrophy of nant transformation into adenocarcinoma o f the fcPE.1 ■
Many Cl Ш РЬ are associated with either a relative or an
the Retinal Pigment Epithelium (CHRPE) absolute scotoma corresponding to the site of Lhe lesion.IJ
SoHtary-type OEElPHs are we 11-demarcated, slightly ele­ CEIRPEi are hypoautofluorescent exhibiting mild hyper­
vated. gray-brown to black, oval, round, or occasionally auto fluoreseuce of the lacunae:E-luorescein angiography
geographic lesions with smooth or scalloped margins in patients with lightly pigmented fundi shows obstruction
(E'igures 1 2 .0 ]- 1 2 .0 3 J. They are usually soliLary but may of the background choroidal fluorescence in the area of the
be multiple and grouped in a pattern suggesting animal lesion except in the fenestrated areas o f [typopigmentation
Lracks (I'igure 12.03 А). А C H R PE may occur anywhere in (figure 12.QIC). Angiographic evideuce o f alterations in
the fundus.,J HovveVM, Cl EliPli in macula and juxtapapil- the structure and permeability o f the relinal vessels overly­
Eaiy location are rare."'1-1'Iliere is often a halo o f depig - ing these lesions may occasionally o c c u r . l h i s includes
mentalion just inside the outer edge of these lesions capillar}1,nonperfusion, capillar}1,leakage, and chorioretinal
(E'igure 12,011 and E'}. Although most CEIREJE: are between anastomosis. Optical coherence tomography ( О С I') reveals
one and two disc diameters, some may occupy an area thinning of overlying relina with overall thickening of RHEi
equa] to one quad rani of the fundus (Kigure 12.01 ft], 'I hey layer, excepl in the region of lacunae, where RPE thinning
have been observed in newborns. : Hypopigmented or is expected (figure 12.021 and J}.-' :
 I Lislopathologically C l LRPli- lesions are cjbiractfri2ed by
a single layer of enlarged RE^i cells containing macromela­
nin granules that may be associated wilh varying degrees
d f degeneration o f the overlying outer relinal layers (figure
12.02)/'-1i--4' -'й Some degree o f К I1]: hyperplasia may л] so
be evident2, Absence o f lipofuscin in the hypertrophied
1-1.Г I. il 11^ suggests :r,x: tluir i:u ^paeit' Lo p 1i й ^ кт I ^e
and digest photoreceptor outer segments may be respon­
sible for lhe receptor cell degeneration so often present
overlying these lesions.-" 'This may explain the Lhinning
o f the overlying neurosensory relina seen on O C I {figure
12.02i and I), lhe structure of the macromelanosomes
in C H R P ] : is similar to that described in X-l inked ocular
albinism? ' -v
The differential diagnosis o f Ci ERPL includes choroidal
melanocylic nevi. secondary and primary hyperplasia o f
the ДЕЧ:, pigmented hypertrophic chorioretinal scars, and
geographic dark fundus patches that are probably caused
by subretinal bleeding and hemosiderin deposits, usually
occurring in patients with sickle-cell disease (see Figures
6.59С and 1) nind 6.58 Ihe large lesions, if not viewed
binocularly, may be mistaken for malignant melanomas o f
the choroid {Figure 12.0111).
'i'hese lesions are similar hislopathologically to lesions
referred lo as congenital grouped pigmentation of the Ri'li
(see next subsection). Hypertrophy of the RPK has been
identified histopalhologically as being pnirt of combined
RPli and retinal hamartomas {see figures 12. Oft К and
U.lOt).
12.0(2 Histopathologic findings in congenital
hvpertrophv of Ihtr retinal pigment epithelium
tt'HRPE).
A-D: Clinicopalhulogic correlation o f a coin-shaped, flat,
piujmenled Itsinprl noLud cn ^ross exam ination Df" an autopsy
eye (A), Nole the nonpi^menled ha In jusl inside lhe mar­
gins of lhe p№nfl^SVt^ lesion. l-flstdHfftholofjic вд»mination
revealed a pigmented lum ar lo he composed of a single layer
□I large RPE cells (right haEl of photomicrograph. E3). The
main body of Lhe lesion was separated from the tiormal sur­
rounding RL’L by a haio ol parLh depigmenfed КГЬ ■arrows,
[J i. Them; was exlensive degeneration of the ouler layers of
relina overlying Lhe entire lesion. A high-puwer v ie w of Lhe
lesion revealed large КЗ^Е cells packed w ilh lar^e^ round
melanin granules O . i Com pare with lhe normal surrounding
R P t Tn L>.>
E: Electron m i<Irascopic view ol lhe normal K P l (left sidcv
and C H R l'l RPE Iri^hl sidej in [he siimc case illustrated in
A-D. Nolo ihitkenin^ cif lhe basement membrane (bmi of (he
К PE.
F and 0 : Cliiucopatholcigic correla Li on of til IК Kb associated
wiLh a large central lenesLmted area noLed on gross examina­
tion o f an auLopsy eye i.F i. I'hoLDmicioyraph o f the margin
Iarrow, C l of Ihe hypertrophied R P t to Lhe left of lhe afraw
and Lhe cenlral fenestrated area shuwed loss of RPE in Lhe
fenesLraled area and proliferation of [ilia I сю I Is itlong lhe
inner sunat.e o f llruchV membrane (G).
H : Hislorjiilholojiic condition of another palienl with O IK P b
stuiwing a sharp line of furuticn 'a rro w I separating the nor­
mal Й.РЁ en the lefl side of the pholomicrograph and Lhe
hypertrophy of lh e R P t on lh e riK.bt side. N o le chat Uruuh’s
membrane appears thickened and Lhere is alrophy of Lhe
unfhuJying choriocapiHaris.
I and J: Fundus appearance of asymptomatic solitary C H R P E
detected on a routine enaminalion (I). O ptical coherence
tomography shows lhinning of Ihe ц№г|ун>1й retina and
prominence of Lhe RPE layer (Jl.
ly W .im J P—H Irtwri U u crin e r.'i
' —
Multiple CHRPE Associated with Familial
Adenomatous Polyposis and Gardner's
Syndrome
Multiple isolated CEIRPEi lesions occur usually in both
eyes of a high percentage of patients with this dominantly
inherited familial cancer syndrome that includes intestinal
polyposis, osteomas of the skull, and various soft-tissue
tumors, Induding fibromas, lipomas.. and epidermal and
sebaceous C A T its .I,r,,;:- Jf<- : 1 i h e r i b [( f o r intestinal malig­
nancy during adult life i s virtually 100%. The soft-tissue
tumors tend to occur during Lhe first two decades, the bony
tumors in the second, decade, and the polyps in adulthood
(mean age 30 yeans). Osteomas of the orbit may occur.'1'
Approximately 50% o f patients will develop adenocarci­
noma o f the colon by 35 years of age. ihere is a di^pro-
porLionate ris-k o f other cancers (carcinoma o f ampulla
o f Vater- adrenal gland, thyroid gland, and bladder J, a
variety o f sarcomas., and neuroepithelial tumors (Turcot
syndrome) (ligure I2.03G-E).1, Multiple C H A PE affect­
ing both eyes is a reliable m arker for Gardner's syndrome.
Multiple GEIRPE: appears to be specific for Gardner's
syndrome and is not found in the other familial intes-
Linal polyposis syndromes (familial polyposis without
exlraintestinal manifestations. Peulz-Jegheft syndrome)
or in patients wilh familial non polyposis colorectal can­
cers." ' lhe C H ftP E lesions in Gardner's syndrome often
show a peculiar oval shape with a fishtail-1ike change a l
one or both poles [rigure l2.03Cr E, and K j.1' In some
cases the lesions appear lo be located in close approxi­
mation lo lhe major retinal vessels and may be associ­
ated with abnormalities in the overlying retinal vessels.'1''
Histopathologicallyr some of the lesions appear similar
to solitary GEIRI]El. Others show in addition hamartoma-
Lous malformations of the RPE featuring cellular hypertro­
phy, hyperplasia, and retinal invasion, and formation of a
mushroom-shaped tumor [E'igure 12.ОЗК and l.|.' 1j:
E i .03 Fam ilial m u lt if o c a l c o n g e n it a l h y p e r t r o p h y of
the re tin a l p ig m e n t e p i t h e l i u m t C H K P E ) .
Л -F: t^ulljple, (jvsl jfeas of flat CJHRFJli yveija nr-eserl Ы1дС<?г-
fiI!у in- lhe ЗП-yebir-old mol her 'A), the fl-Vgar-old sun
tind lhe Ш -ytw-uld diiiij^Her (E and Fl. Note? Lhe depi^-
mented halo r e a r the margin o f the les-ions,. [heir radial
ипегтЬI run in n^pect lo Lhe posterior pote^ and the fish­
tail-shaped EiypdpigO^entBd лгеа :*1 иле иг IjoLh ends; o f the
leiionu (arrows!. The l^ lo lls showed varying du^nees o f pig­
mentation. The eye екатагяМопы were crthenvise normal in
these patients-. M ed ical evaluating failed I d find evid en ce of
inleslinal polypotis or other disease.
G —I: Turcot's svndium e w ilh m ultiple C H R P E (G): adenom a­
tous polyps of the stomach,. duodenum, and c o lo r (I); a r d
a Lerehelbar ntedutlokda&tefrTia (arrow, H: occurred m this
20-yciLir-old miin, w h o pnpsenlcdil b nausea. headaches,
and vomiting дЛег head trauma.
3 лпН k: HisLopatholos^y of С Й Й РЕ lesions found in Lhe eyes
o f a patient with Gardner's syndrome. Hypertrophy o f K P t
(J). Hyperplasia iind hypertrophy o;i КГБ !K'.
L: Hypertrophy and hyperplasia of К ГЕ with extension
through I be lull ibickness of line relina.
I t ] - 1 lrr:.in M u r r d u n f l . a l I .srn f К ftfcun l r . i t u u l s i uL ,s l." ' i
Patients with bilateral lesions, multiple lesions (more
ihan 4), or bolh are specific (specificity, 0.95) and sensi­
tive (sensitivity, 0,78) markers for G ard tier's syndrome.1' A
review of published studies regarding genotype-phenotype
correlation suggests that CHRPH is associated with muta­
tions between codons 31j and 1444 of lhe adenomaLous
polyposis coli {А ГС ] gene.46 The gene for adenomatous
polyposis o f the colon (A PC j was found Lo be on 5qll-22
by Bodmer et aI.'1 There is no evidence that typical solitary
or grouped C H R P E lesions represent a marker for Gardner's
syndrome.2"' .Multifocal CZJ IRJ^H lesions have occurred in a
family with microcephaly and fe^tmeflexaa46 and in one
family in Miami without aiiy other abnormalities (figure
11.03):14
Grouped-Type Congenital Pigmented
Nevi ot the Retinal Pigment Epithelium,
'Bear Tracks"
Jhis is a rare congenital щрща1у first described in IB6S by
Mauthner.-1^ It is characterized bv sharp ly circumscribed.,
small, variably sized, pigment spots lh лL are often arranged
in groups lo resemble the footprints of anlm ab (E'igure
12.04).lU' '' '['hey are usually grouped in one sector of lhe
fundus wilh the smellier spots located at the apex directed
Loward lhe oplic disc.""1 Jhey infrequently are present in the
macular area. Extensive areas of the fundus may be affected
and be associated wilh bilateral involvement (E'igure
12.04E> and li) ." " ~"л l"he lesions can occasionally be quite
I : l)4 C o n g e n it a l g r o u p e d p i g m e n t a t io n o f the r e tin a I
p ig m e n t e p it h e liu m (R P E b
Л -С : U niocular involvem ent in three patienls. Each showed
lesions ir d r e quadrant or less. N o ne had m a c J № involve­
ment. All had normal vibUiil Eumjlion.
LI Lind E: Marked peripheral liWoJvertiBfit in both eves о I this
patient with ftorma.I visual fun с Iion.
F: Higher-power v ie w of tEie upper пдыЗ quadrant of the
riu.ii I furious:
G : Several large peripheral zones ol hypertruphiy of the KFE
accom panied ^ruuped pigmentation in this patienl.
H - J: A 3 Ь-year-old asymptomatic African Am erican w om an
with large lesions resemljlin^ "tilepEujnl lra< ks~
К and L: a 3-year-old boy with large lesions in nasal retina.
к -and L. c i j u r k 't y ul U r. J J . iv k ! f1.-1 г г i з l i г i . ■

lar^e and simulate "elephant tracks от grizzly bear tracks"

(E'igure 12.04J E—L), a finding that has been noted as early
as 1526." Familial cases involving two successive genera­
tions are reported.'1 N Twb sisters, one With pigmented
bear tracks and the other with albinotic spots, have beer]
seen.1'-' Whether the grouped pigmentation Hind the other
associations in a patient with microcephaly, mild mental
retardation- and deletions of ]3q33.3-q34 and ] l p 15.4 are
causally related cannot be established.'113 The retina over­
lying "bear tracks" appears normal bio-microscopically
and angiographically/1 Eilectro-oculographic findings are
normal. 'Ihese lesions are believed to be stationary, but
long-term follow-up studies have not been done. C rouped
nevi have infrequently occurred in association wilh other
anomalies or disorders including retinoblastoma and skin
t ^ p e if ig m e ^ t a ^ n i^ ' ■и -*6
These lesions hi stopatho logically are similar to
C JE K E ] Ei with increased number of pigment granules in
normal-sized Etrt cells/167 Unlike C lIK l’ti most of the
melanin granules retain their elEipsoidal shape and hyper­
trophy and hyperplasia of the KFE are less prominent/
Clinically, some palients may show lesions typical of both
grouped nevi and C H E P ii (figures 12.0] A and I2.04G).
Grouped-Type Congenital Pigmented I : l)4 Congenital grouped pigmentation of the retinal
pigment epithelium (RPEb
Nevi bf the Retinal Pigment Epithelium,
Л -С : U niocular involvem ent in three patients. Each showed
'Bear Tracks" lesions ir d r e quadrant less. N o ne had nmculnr rnv-olve-
Jhis is a rare congenital щрща1у first described in IB6S by mont. All had normal vibUiil Eumjlion.
Mauthner.-1^ It is characterized bv sharp ly circumscribed., LI iind E: Marked peripheral involvement in both uves о I this
patient with гюгггм! visual fun с Iion.
small, variably sized., pigment spots lhaL are oflen arranged
F: Higher-power v ie w of tbe upper nasa] quadrant of the
in groups lo resemble the footprints of animals (E'igure riu.ii I furious:
12.04).lU' '' They are usually grouped in one sector of the G : Several large peripheral zones о I hypertrophy of the Hf’t
fundus wilh the smaller spots located at the apex directed accom panied grouped pigmentation in ihis patienl.
tow aid ihe oplic disc.""1Jbey infrequently are present in the H-J: A 3 Ь-year-old asymptomatic AlVccan Am erican w om an
macular area. Extensive areas of the fundus may be affected with largo Зон ion к resembling "tilephanl lra< ks~
and be associated with bilateral involvement (E'igure К and L: a 3-year-old boy with large lesions in nasal relina.
12.04E> and li) ." " ~"л l"he lesions can occasionally be quite к -and L. ciju rk'ty ul I >r. JJ. ivk ! f1.-1 ггiзliгi . ■
lar^e and simulate "elephant tracks от grizzly bear tracks"
(E'igure 12.04J E—L), a finding that has been noted as early
as 1526." Familial cases involving two successive genera­
tions are reported.'1 N itoo sisters, one With pigmented
hear tracks and the other with albinotic spots, have beer]
seen.1'-' Whether the grouped pigmentation Hind the other
associations in a patient with microcephaly, mild mental
retardation- and deletions of 13q33.3-q34 and lip 15.4 are
causally related cannot be established.'113 The relina over­
lying "bear tracks" appears normal hio-microscopically
and angiographically/1 Edectro-oculographic findings are
normal. 'Ihese lesions are believed to be stationary, but
long-term follow-up studies have not been done. Ci rouped
nevi have infrequently occurred in association wilh other
anomalies or disorders including retinoblastoma and skin
t ^ p e if ig m e ^ t a ^ n i^ ' ■и -*6
'I'hese lesions hi stopatho logically are similar to
C JE K E ] Ei with increased number of pigment granules in
normal-sized R PE cells/167 Unlike C lIK l’ti most of the
melanin granules retain their elEipsoidal shape and hyper­
trophy and hyperplasia of the KFE are less prominent.^
Clinically, some palients may show lesions typical of both
grouped nevi and C H E P ii (figures 12.01 A and I2.04G).

ALB IN O T I C A N D N O N P I G M E N T E D
NEVI O F THE RETENAL P I G M E N T
EPITHELIUM
Grouped-Type Congenital Albinotie
and Hypomefanotic Nevi of the Retinal
Pigment Epithelium, "Polar Bear Tracks''
Congenital grouped albinotic nevi are multiple, while,
variably sized spots involving lhe JtPEi in а pattern simi-
Ear to thal in congenital grouped pigmentation of lhe R P E
(E-'igure 12.05).1"1'1'Ji,-:">'lhey may occur in one or both eyes
and may be mistaken ft)г other flecked retina diseases (e.g.,
drusen, fundus flavimaculalus, paltern dystrophy, fundus
albipunclatus, and Gaucbers disease). Like pigmented
'"bear tracks/ these albi not ic spols occur rarely and lend
to be more numerous and larger in the peripheral fun­
dus, and they usually do not involve die macular area,
lliey appear to represent focal thickening of the ftP E that
is filled wilh a while material. This while material may be
diffusely distributed or may be more concentrated in lhe
periphery o f the lesion (Figure 32.05A and C). !n some
cases the spots appear to be devoid of while material,
and the underlying choroidal vessels are visible. In other
cases, some of the spots may appear Lo contain dark gray
pigment. The overlying retina appears normal, except thal
Earner retinal vesseis may appear Lo be localEy narrowed
(E-'igure 12.05 C and L>). ЧЪе lesions are probably relatively
stable, but further long-lerm follow-up studies are required
to document this. Although considered to be function­
ally o f no significance, one patient with macular as well as
peripheral lesions develo ped neovascularization (Figure
12.05C: and It).
Muorescein angiography shows variable degrees o f
transmission of the choroidal fluorescence through these
Eesions [Figure 12.05b).
Although longer follow-up o f ihese rarely encountered
patients is required, it is probable that the albinotic spots
represent a congenital anomaly o f Lhe ЙРЕ closely akin
E2.EH C o n g e n it a l g r o u p e d re tin a l p ig m e n t e p it h e liu m
alb in o tic nevE.
A—С : Except for lh e albinolic spots [he results ul an eye
examination Iha I induded color visiun testing eEeclroreLi-
nograpEiy, electro-oculography, and dark-adapUilicn studies
were normal in this heallhy 1 5-year-old girl. N o le Lhe periph­
eral d iни:E>LrLion of w hile malerial in some c f Iho larger spols
iarrows, A and Klijjhl n.m owing al a jSefinal artery over lying
one spt>1 l.ifmiv, C). Angiography showed Variable Iranstrfii-
моп o1 Ibe choroidal fluorescence through Lhe spots Ш).
D and E: Albfnolic spots, in o re eye o f a 40-year-old asymp-
Ео г Ги й с w n n 'jiin . Nole narrowing a t retina] vein (a rro w over­
lying a liHrge spol.
F : A lb in o !ic spots in o n e e y e of an a s y m p to m a lic Y o u n g m a n .
С and EH: T b is heallhiy 1 4 -year-old дГг1 w a s o lis e rv e d for 3
увщ & w i lb g jo u p tid fllb iiu jtic нроЕн in IvuLh eyes b e fo re s h e
wan seen I J e c a u s of loss o f o en lral v is io n in Lhe le » e y e
a s s o c ia te d w ilh cE io ro id a l n e o v a s c u la riz a tio n (arro w , H ). H e r
e le c lro re ti n o g rap h ic an d e le c ln o - o c u lo g ja p h ic Findings w e r e
n o rm a l.
i l J Jr td : . O Q U r C t s v ' tnl I J r . A l v ; i r u K L u t r i ^ u t ; ^ ( .j . i n d H , L io u r lL ^ y
Dr. H jrrv W. i'vnn.i
lo conge nital grouped hype rpigme mat ion of the KPEi.. let
lhe case o f the aEbinolic spots, the RPH cells appear lo be
stuffed with a while material, possibly an abnormal pre­
cursor of melanin ralher than enlaiged melanin granules
as in grouped byperpiigmentalion of lhe KE’E;.
Dr. Gass believed lhal these aibinotic RPH spols are
identicaE lo those reported by Kandori and associnles04" 1
in association with stationary night blindness thal was
manifest primarily by abnormal dark adaptation. К one of
lhe four patients seen at the Bascom Palmer Eiye Institute
had nyctalopia. Studies, including dark adaptation, elec-
ironeltnograpby, and electro-oculography, were normal in
lhe two patienLs illustrated in Figure I2.05A-C, G, and FI.
Parke et al."^ reported similar white spols in one o f two
siblings with pigmented RPE lesions, microcephaly, men­
tal retardation, and autosoma I-dominant hyperreflexia.
Solitary-Type Hypomelanotic and
Albinotrc Nevi (Torpedo Maculopathy)
]he&e solila ry-, sharply circumscribed, hypopigmented
reddish-orange or w hile lesions of lhe RPK, which have
been previously referred lo as "congenital hypomelanotic
freckle" or 'retinal al binotic spots/ are most frequently
observed in tbe peripheral fundus and in the temporal
half Of lhe macula.1-2 7:1 I’hese Ialter lesions oflen have
an ova] or fish -shaped appearance similar lo lhal seen in
the C\ !RPE lesions associated wilh Cardnei's syndrome
(E'igure 12.06A and & - f).7j '['hey are often discovered on
routine eye examination in children, they m a y 1, or may
not be associated with a demonstrable visual field defect.
Although they may show a slight milky while color, Lhey
are rarely as densely white as the grouped al binotic R Pli
nevi. Unlike most acquired atrophic lesions o f the RPE,
hypopigmented R P t nevi typically have no margin or
irregular hyperpigmentation. Angiographically the chorio-
capillaris underlying these lesions appears to he norma!
(E'igure I2.06B and С). О С Г done on two patients by
Golchet et al. has shown thin RPli with increased signal trans­
mission in the choroid.r<i Bolh patients showed a "cleft" in
the outer relina associated with loss of photoreceptors, irreg­
ular edges of the residua] photoreceptors, and thinning of Lhe
outer plexiform layer. lhe OCT finding remained unchanged
o vert years of follow-up in one patient, lhe authors inferred
that "something occupied the cleft, the nature of which is
unknown/ It is Likely lhal this space is empty due lo loss of
the overlying photoreceptors; boLh palients had an absolute
scotoma corresponding to the lesion, ihe O CJ' appearance
has led to speculation lhal the lesion may not be a nevus, but
rather a localized congenital ihin or atrophic RPH 11
W hy this bears lhe same shape as a torpedo or fish­
shaped C H R PE (figure 12.0ЭА-К) as seen in patients with
intestinal polyposis (Gardner's) is unclear, if il indeed is
not a CH RPE. Il is likely lhe same trigger causes the lesions
in hoLh these conditions, but the pigment epithelium is
devoid o f melanosomes here while the Gardner's eyes
develop an excess of them. Choroidal neovascularization
arising al the edge o f a lesion is rare but reported (irigure
12.0GJ-L). Microscopically, hypopigmented kl’h nevi
12.06 Large solitary ame Ian otic spot or nevus of the
retinal pigment epithelium (RPEk
A -С: Am eLinotic K P t nevus ffrsL noled on a routine eye
examination & years previously iri art asymptomatic 51-year-
old black wom an w ith £ d fl 5 visual acuity bilaterally.
5tie had only a faint relative scoLoma to 3/1000 color best
objects. Note lhe relatively intact choriocapillaris iK and C:.
D ; A m e lan o tk nevus in a 12-year-old boy with normal acu ­
ity. Am sler £*rid.. and Coldm ann visual ield ejLaminalions.
E: laired a melanotic nt?vi in an asymp1omaLic palienl.
F: Hypopigmented R P t nevus wilh locus of RPE hyperpEasia
and atrophy.
G-l: Amelanotrc nevus or freckle noted on Jjioss examina­
tion of a fresh eye lum-oved ,it autopsy -Cl. Histopalbo3o£>ac
ека mi nation revealed л focal area of depigmentaLron of Lhe
a ni factitiously -riel ached PPE La nows, H 1. A high-power v ie w
showed a sharp Iransilion (arrows!1 between the nonpig-
mtmtfd, f(aliened к PE: tolls and the relatively normal, sur­
rounding RPE cells I arrows, I .
|-L: Л 17-vear-old malt' wiLh a known hislory of a spol in Lhe
ji II i.-yi presented vvil l vision i ;■ л и :. A r: i\ pn| ii..' -
mented lesion under lhe fovea is partlv covered by a thin
Eayer o f subreLinal blood adjacent to a circular pigmented
type 2 C N V M , temporal It) which is a crescent of sui>relinal
fluid. The angiogram shows hyperfluorescenoe of Lhe partly
oEjscured torpedo lesion, Lbe lacy C N V M . and lhe surround­
ing SRF. The palienl received three infections of monthly
intiavifreal bfivaclZumab resulting in involution of the C N V M .
resolution o f Lhe SKh, anti return of his vision Iо 2СУ20.
M-N: A 17 year old with лп atypical shape and Ioca Iion of
an antelanotiL spot LhaL was first seen 10 years previously.
Note Ihe visible choroidal vessels Linder the thinned oufi
depigmented KE3t (M). H yp o aulofluorescence of the lesion
implies lack of p ic n ic nL granules w ilhin the RPE 1hal renders
Lhe lesion amelanolic, corroborating Ihe histology seen in 3-1
and I (N1.
iD I'lnpp CtMjWpn rmd Cad * 1 American fv11.:cJi■
!LiI Asmji i.iIioi i. Л1
ri^hls reHervt<d. tr J-Ц. cjlxjiI k v uf L>r. Mjrk I. LJjily: С—I [Him
show a shaup iransitlon from fo rm al R[:b lo flat nonplg-
menled epilhetium fbigune 12.06G and 111 i4-72!?- Unlike
the presentation in most cases o f congenital hypertrophy
o f the RPEi, the overlying relina is normal. The underlying
choroid is also unaffected. So far there are no histopatho­
logic studies of solitary nevi that clinically appear while.
C O N G E N I T A L SIMPLE
H A M A R T O M A OF THE RETINAL
P I G M E N T EPITHELIUM
(C O N G E N IT A L HYPERPLASIA
OF THE RETINAL P I G M E N T
EPITHELIUM, P I G M E N T EPITHELIAL
ADENOMA)
Children as welE as adults wilh focal, solitary, nodular
black subretinal lesions that extend anteriorly Into and usu­
ally Lbrough the entire thickness of Lhe retinni that probably
are hamarLomas composed of hyperplastic RHi haw been
observed [llgure 12.CJ7J.1" 1 Ihe hamartomas a lt associated
wilh minimal dilatation of the feeding and draining relinal
vessels, retinal exudation, surrounding relink traction, and
pigmented viLreous cells (figure 12.07Л).' Like solitary
hyponielanolic RPE nevi, these lesions are frequently dis­
covered in the temporal macular area o f normal children or
young adults on routine eye examination. fluorescein angi­
ography reveals Lhal these lesions are non fluorescenl early
but may show evidence o f some staining lale or a slight
halo o f fluorescence at the border (I'igure 12.071J and C).
]he lesions are echodense on H-scan and display high inter­
nal reflectivity on А-scan. Ihree patlerns o f retinal involve­
ment have been illustrated by Gass: superficial involvement
Еп the retina, full-thickness retinal involvement with preret-
inal extension and fuil-thickness involvement with intrinsic
vascularization (E'igure 12.07C;). '
higLire 12.U7 Co ngen itnE hyperp Iasia of t h e re tiпд E
pigmenl epithelium (RPE).
A-C: O n a roLilinu- eye долгиiпat ion я fbcal elevalud tifijfc
mented lesion IКлL eaLended through the full Ibkfcness of
Ihe retina was nuled ]n the rij^hl m JtL ila of an fisym ptoWWic
12-year-ofd girl (A). Note [he edge of lbe ano m alous uptic
disc (A and С". V-1uurescein argiography showed Ibal Lbe
lesion extended ibruu^h and covered Ihe surface of lbe rel­
ir a and lhal it stained in the late photographs (Ы and Cf.
D and E: An elevated pigmented lesion ratendinj’ ihrtmgh
Lhe full ihickness of Lhe relina was noted in an asvm plom alic
57-year-old man. HEis visliflif atuiLy in 1be riyhl eve wan 20/25
and in Ihe left eye w as 20/20. He had a pasL history o f hav­
ing w aLilied an eclipse as a c. h iI cl. lb e left fundus was nor­
mal Anj^icj^iaphv Tovealed LbaL Lhe lesion t r e n d e d ibrougb
Lhe full thickness of Lhe lelina, obscured die reLinii! vessels,
and slained ceHtrally in the late pholographs It:.
F: This pigmented lesLon involving the full ibicknens o f Lbe
relina was discovered in an 11-year-old girE w hose visual
atLiilv in lhe гij^Hl eye was 20Л5 and in lbe* left eye was
20/20. The left fundus was normal.
G : [ntraretina I congenital KKt hyperplasia. I , Superficial. 2,
FJreretinal extension. 3, Preretina I extension wiLh superficial
vasculari nation.
Il-, cjrtu rlc iy i >
1 |}г. K. кеп п м п Cjuerry: Cj ftiirti G j i b . 1
To date no change in the size o f these lesions has
been documented. Some of the Earge pigment epithelial
adenomas in eyes enucleated because o f suspected cho­
roidal melanomas probabK are also o f developmental
C O M B I N E D P I G M E N T EPITHELIAL
A N D RETINAL H A M A R T O M A
Combined pigmenl epithelial and retinal hamartomas are
peculiar, slightly eLeveled, partly pigmented lesions.. which
may bft mistaken for a postinfbmmiilory scar or a malig­
nant melanoma and which may be present anywhop in
the fundus. 1,s* '' lhe clinical history.. appearance o f the
tumor, and its structure vary'wilh its location.
Combined Pigment Epithelial and Retinal
Hamartoma Involving the Optic Disc
Patients with tumors Lhat involve the optic nerve head
and jujitapapiJlary retina typically are seen in voting adults
because bf blurred and distorted vision in one eye. '['he
visual acuity is usually 20/100 or belter. IJiomicroscopic
examination reveals an ill-defined, slightly elevated, partly
pigmented tumor involving part of the optic nerve head
and adjacent retina [Figure 12.08). lhe tumor is com­
posed ol" a fine granular distribution o f pigment, giving it a
charcoal-gray filigree appearance.' ■ ifte pres­
ence of many fine capillaries within the tumor may be
partly obscured from view by a semitranslucent gray mem­
brane Lhat is always present on the inner retinal surface.
Palients become symptomatic either because of meta-
mo rphopsia caused by contraction of this membrane that
produces traction folds in the retina that extend into the
cenLral macular area (figure 12.0SA), or less frequently
because o f subretinal and intraretinal exudation derived
from the capillary component o f the tumor [E'igure
12.0til>]. Lhis exudation may reabsorb spontaneously and
leave atrophic changes in the RPL surrounding the tumor.
Other complications that may occur infrequently include
choroidal neovascularization, retinal hemorrhages, and
vitreous hemorrhages.i:-: 1M lhe early phases of angiog­
raphy demonstrate dilated, multiple, fine blood vessels
within the tumor, and later phases show evidence o f leak­
age of dye from these vessels (l:igure 12.0SB, С, E, i; fi,
and [). - ' l he clinical appearance and fluorescein
angiogram features are enough to make the diagnosis in
mosl cases. О С Г is useful in distinguishing lesions that are
not very thick from epiretinal membranes by detecting dis­
organized underlying retina.IU-' Vitreous traction if presenL
may also be detected, and thus help in selecting cases th at
rnay have a potential for visual improvement with vitrec­
tomy and membrane peel Lo relieve traction.
11islopathologically, the optic disc tumors show evi­
dence o f a hamartomatous mal forma Lion involving
I 2.0Я Combined retinal pigmenl epithelium and
retinal hamartoma iCRPE-RbN of lhe justapapiflary
retina and op lit disc head.
Я —Сз A c irc limscribed, siighLlу elevated, linely motLled, pig­
mented Eeslon was- noted in a 21-year-old man w ilh a 1-year
history ol progressive distortion ul" Lhe vision in his lefl eye.
Two years previously his visual acuity had been 20/20. He
had mullipLe llat pigmented lesions tin lhe bullocks and
arms. His pair m edical history was otherwise negative. Visual
acuily in lhe lefl eve was 20/50. Flecks of piemen Led tissue
extended anleriurly into lhe thickened feflna and optic, nerve
tissue and partly covered the m ajor retinal vessels л? they
entered the optic nerve bend lAl. This was associated w ilh
an epi relinal gli:il membrane. F-’rominsnl relinal Inn.lien folds
extended from ill is membrane into Lhe macula. There were
many fine, dilated, tortuous capillaries within the Iитог.
TFiese w ere best seen angiographlcally |0f. There was slight
e a te jjB Ol dve from vessels in Lhe Liter angio^r^mis ft:.
D -F: Serous detachment of lF>e macula and ciivinale roljnopa-
Lh1.- caused Ijy a jUxtapaprllatV retinal and К PL hamartoma in
a 55-year-old woman (t>k Angiography revealed a capillary
angpomatdLis component of this lesion i l and F, slnreoj.
G-F: S-гпча11 hvpopii^nenled cottibineq R P t a ltd reLinal h^mar-
Loma in a 66-year-old asympLomaLic man w ho was subjected
ol having ischemic optic neurupalhy <G). An epirelinal mem­
brane on the surface of Lhe lesion partlv obscu-red lhe relinal
vessels and (he m allled pigmentation w ilh in Lhe lumor (G|.
Angiography revealed evidence ol the capillary angiomatous
nature of d::s lesion as w ell as some dihtLion of lhe relinal
capillaries in 1he papi 11omac ul ar bundle tH anti I),
f and K: ClinicopalFioiagic correla Lion o f a j if я Lapap i 11ary
CRPE-FiE-l in а 2 У-year-old man w ilh an Й-woek hfalorV of
blurred vit-itjn in his left eve l.i. M elanom a was suspucled,
and lhe eye was enuclealed. H islopalhologic examination
revealed disorganizalion of Lhe normal атс. h i Lect u re of Lhe
optic nerve head and retina associated with hyperplasia of
the neLinal brood vessels, KPE. and glial Liss-ue (K). Lords and
sheels o f К PE proliferation extended throughout lhe tumor
and surrounded blood Vessels lartowsr Kj. \ o te the prcjlitera­
tion of fibrous 1issue near Lhe surface of the retina.
lA J IrcHTi V t ig c t u l . 1!. ’ I .1 r : I К frcnn' ,Vi,ic h n r i c r . ' ' I 14& v. A n ilt ii.iii
M r jd iL il Л ^ ю ь ;.:1 н м 1 . ЛИ r ig h t s г г -.c;rvi;(E. ■
hyperplasia of the RPL.. glial cells, and blood vessels
(I'igure 12.0Д] and Many of these
lesions remijd stable. Some J¥tay develop exudative
changes and show an Increase in opacification of the
glial component o f the tumor, lh e surface glial mem­
brane causing Lhe retinal folding is an integral pari of the
tumor and accounts Гог the fact that surgical sLripping of
the membrane is difficult and has little chance of restoring
central vlsioit:104' " n
 These tumors* particularly if lightly pigmented. when
discovered in infants or young children may be mi stake n
for retinoblastoma and Т о л ж и гИ г я н й . [ л patients with
more- heavily pigmented tumors, lhe differential diagnosis
includes melanocytoma, malignant melanoma, and reactive
hyperplasia o f the R T L l he optic disc tumors wilh minimal
pigmentation may be difficult or impossible lo differenti­
ate from capillary angiomas, astrocytic hamartoma or from
epipapillary and juxtapapillaiy epi relinal membranes asso­
ciated wilh other causes.]Ll|h One patienls hypopigmented
tumor was misdiagnosed as ischemic optic neuropathy
[E'igure I2.08G-1J. Reactive proliferation of relinal endo­
thelial, glial nind Rl’E: cells may duplicate any o f the retina!
and RPE hamartomas. Spontaneous development of lesions
indistinguishable from a juxlapapillary and a peripheral
combined pigment epithelial and retinal hamartoma in two
adult patients where previously there was no lesion has been
reported (see figure r2 .J3 G and El, below].1'' Development
o f s im ila r tumors in children wilh previous optic disc edema
has been seen and the authors speculate that the lesion may
not be a hamartoma, but rather an acquired glia! resp o n se.'
Shields el nil. in their recent review o f 77 patients found
the mean age at diagnosis Lo be 7 months for macular
and tf months for extramacular lesions, and the youngesl
child was 2 weeks o f age.rj *7- 1[l ll is likely that Lhe
trigger for development o f this disoiganized tumor occurs
in utero or very soon postnatally and the tumor continues
to grow and remodel after birth {C Shields, personal com-
municationj. Surgical intervention wilh vitrectomy and
epi retina I membrane peel has shown a minimal to mod-
еЫ visual improvement in few cases.|,л-11:-11'■These cases
should be selected carefully; full-thick ness macular holes
have occurred when the membrane is intrinsically woven
into the lesion.
Combined Pigment Epithelial and
Retinal Hamartoma Without Optic Oise
Involvement
I t iese tumors, which art? often only slightly elevated, are
usually discovered in one eye o f an infant or child with
strabismus and subnormal visual a c u i t y . ' 11 'Ihey
are associated with increased number dilation, and tor­
tuosity of the relinal vessels, evidence of gray epi retinal
fibrous tissue, and hypeipigraentation confined to the
level of the RPE, This pigmenlation is greatest al the bor­
der of the lesion, where its feathery edges blend imper­
ceptibly into lhe surrounding normal RPE, Unlike tumors
involving the optic disc, these show no evidence o f R H i
cells or capillary angiomatous Lissue near their inner sur­
face. I'hese tumors Olay involve lhe peripapillary area
Fig u re 12>!9 C o m b in e d re tin a l p ig m e n t e p ith e liu m
an d re tin a l h a m a rto m a s (C R P E - R H ) w ith o u t in trinsic
in v o lv e m e n t o f the o p tic disc h e a d .
A: CbiPE-RH in the m acula o f [he lefl eye of an otherwise
healthy 7-year-old jjiri With amblvopia in lbe left eye.
B - D : CK3J t-b!H in the mncular region of an В-уеаг-oEd boy
iA . Hhs rij^hl fundus w as normal. Fluorescein angiography
demonstnil-i'd lorlUOsityr dilation, and abnormal permeaEiility
of the retinal vessels in the region o f the tumor (B-Df. Arrows
indicate lhe temporal liorder of the fist pigmented portion of
the tumor tO.
E and F: P^ripherijl CJiiFb-PH simulating a nerin:oblastom,i
unri rnajignapl m ob noma of [he choroid in a iT)-mofilh-
o|d jjid w h o was lbe product of a:i uncom plicated full-Lerm
pregnancy nnd delivery. Her Eiinh wei^hl wan B ib U.ti-J
Al age 5 month-s i п leim i11un I oxotropia was noted. There
wan dragging of lhe retina: vessel* and displacement ot lhe
macula (arrow, F) in a superolemporal direction by a slightly
elcvalecL рл rl I у pigmenled tumor that was localed near the
equal or superotemporalJv : E i. M u ch of the cenlral portion of
Lhe pigmented lesion was obscured by gray-while, semitrans-
iucunL, ihickened relink I tissue and an epi relinal membrane
iL:. Note Lbe dilation and tortuosity of the retinal vessels and
Lhe fealhury ч!рреагаш:е of [he flat piL|mjjn led portion of Lhe
Iи т о г '.arrows, t ' wheru it blended imperceptibly mLo the
normal R P t. By the a fie of 40 monlbb tbt! child's visual acuity
in lhe aflecled eye w h s counJin^ fingers only and the lesion
was unt banned.
G-|: Mkd peripheral C liPE-KH (H i associated w ith heteroto­
pia ol lhe m acula and co n g e n ia l optic disc pit (It. Note the
dilated capillaries and leakage of (luhrescein ЕГ and I .
К and L: HeaElhy 4-year-old boy referred for possible reti­
noblastoma discovered during evaluation of poor vision in
the righl eye. H e bad anisometTopit: amEilyopia w ilb 2Q/frO
vision ^ right eye, and 20/10 vision,, left eye. There was a
slij^hllv elevalcd piymenlud lesion covered by gray-white
retinal Lisbue and lorluous relinal vrssols near the superoLem-
poial border of lbe lefl macula 'Ll.
[A—f fiio:n С ии-. J
(see I'igure 12.1(1. below}, the macula (Figures ! 2.0!> and
12.11), or the peripheral fundus (Figure 12.0 9EI—l_j. Those
in the temporal half o f the eye peripherally are often
associated with displacement of (he macula toward the
lesion (l:igure 12.09C-L). fluorescein angiography usu­
ally shows marked tortuosity and leakage o f dye from the
retinal vessels within these macular and peripheral tumors
(figures I2.09A-L> and 12.1ID-G). lliese patients, mosl
of whom are children, has'e no history of prematurity
and have none of the changes in Lhe far periphery of the
fundus typical of retinopathy o f prematurity. Subretinal
exudation may occasionally occur from the tumor ves­
sels, resulting ill progressive detachment o f the retina,
rubeotic glaucoma, and loss of lhe eye (Figure 12.11 A-C).
 lhe histopathologic findings in the peripheral lesions dif­
fer from those involving the optic disc in that they show
Eets disorganization o f the relink absence of R P t migra­
tion, and less evidence of capillary proliferation within
the relink and evidence o f hypertrophy o f the RPH
(Higuirfe 12.I0D and
E I". I и P e rip a p rlla ry c o m b i n e d r e lin a l p ig m e n t
e p iih e lii r m a n d retin a l h a m a r t o m a ( C K P E - R H ) ,
A—C : CRFJt-Rl-[ ыигтоj n[1:n^j lh " rifihl oplic drsc (ahfraws, A
and H.i in an infam. W ith in ^Efvyral yx'Lirs there whs - further
согик’пзйСюп of the fibrous tissue on the Lumor suria-cte (C).
0 iirtd I : L^r^L1 peripapillary kFE j*nd retinal bamartoiiia in a
1 6-year-old boy. M elanom a Wl1 £ sLJspected, and Lhe eye ^vas
etfludeated. HistopaLholrjyic e^rTiliSjfion revealed hvjrerlro-
phy df lh " Kh^Ei ''arrows, t\ mild dysplania of Ihe геМлчЭ.. and
epi ret rtaJ fibrous tissue.
1.-Ч—( . o u U r t & r o l U r . J r ih n h1. S h t t c k , !r j 1,1 . l i i l I I f r u r n L .t n n . i .mrP
■ ■ l i 4! 4 I r> I I ■ Г ,
W t n ilT i jj- ■'1111■: 11■.■
11 № iJh |.ic.,rm i-.M o ri I r u m lh e Л и ч т и ,m Ji >urn.il o l
С^ > 1 11 !! 1111:11 V. L C ijy r i^l-lL I h lf i j j j l h l ll.l In ll'L I 'ill ■I: ■ ■; L li
 L>r.. Giiss had seen these hamartomas; or lesions simu­
lating thejn, occur in palients with cutaneous hemangio­
mas, X - i inked juvenile reLinoschisiSr j congenital pit o f lhe
optic disc in the opposite eye, and En palients wilh neu­
rofibromatosis (Kigures 12.0УСЗ-1 and 12.11).’’ The nisso-
cialion o f these hamartomas with neurofibromatosis is
iKriV well established.1-'1'1’I:' !:I' 125 Neurofibromatosis has
been subdivided inlo al legist two major disorders. Nh-l
□nd lMH-2, with gene defects on two different chromo­
somes.4 ' lbe combined pigmenl epilhelial and relinal
hamartomas in patienls with neurofibromatosis usually
involve the тэси !а (E'igure 12.IJ), may be bilateral, and
have occurred most commonly in neurofibromatosis type
2 : l-h. i n i j j , 12й
\2. E I Combi tied retinal and re linal p igm e nt
epithelium hnmartomas occurring in patients wilh
n eu rofi broma losisL
Л - t : A com bined КГЬ and retinal biamartOfiti of Ihe |Hac-:
ular region in в 30-month-old yirE with suspected relinu-
blasloma or malignant Йй1айоЦт4 IA and 11^. Lelt esolropia
was noled nl 2 months of aj^e. There лды 1Й£его1егпр$ка(
displacement o f lhe optic nerve head and nulirtal vessels by
a lar^e ■( iul:i disc d iemeteral, elevated, partly pigmented
mass in the macular and param acular areas. The tenlial
portion of the pigmented lesion w as obscured by thickened
LrjinsjIuccnL retin^i tissue dhd a gray QTeretinal membrane.
The patient had sevEFal prominent cafe-a.u-l,iiL spols cn the
abdomen (Q , Several years later she developed an exudalive
mlinal detachrrietft and rufieolic glaucoma, i;nd гай eye was
enudeated.
D - G : Bilateral hypopijjmented com bined relinal and KPE
hamarlormis in ar: infanl w ilh neJroJibrOfnatatis.
H —|: Bilateral hypopigjnenI k J com bined retinaf and RPb
hamartomas in a child With neurn^fifjromatosi^.
I A j n J Ц f r o m C u i a ^ r [ J - C I n t m k t l m e r u ! n l . l ^ j И - J , c jlh j rltib-Y u f
D r. 1й* п tiin g Ы. K lin e :
© @
UNILATERAL RETINAL PIGMENT
EPITHELIAL DYSGENESIS
Variant of Combined Hamartoma of the
Retinal Pigment Epithelium and Retina
in 2002, Cohen el aL reported a condiLion they named
unilateral leopard-spot lesion of the KE4i,'-' and later
renamed it unilateral RRE dysgenesis. lhe lesion is uni­
lateral.. continuous with the optic disc, and characterized
by hyperp}gmental of the l?PE at the edges with Sev­
ern I Li ni form mid-lesion patches of hypopigmented RPE
(lacunae) and a characteristic scalloped margin (Figure
12.!2,\. С, H, and Cj. A few patients also show retinal
vascular telangiectasia, mild fibrous proliferation, and
retinal folds [Figure 12.12C-I} that likely make this con­
dition a forme fruste of combined hamartoma of the RPli
and retin;i. lhe hyperpigmenled RPL is hypofluoieseenl
and the lacunae show transmission hyperfluoresce nee on
angiography. On autofluorescence imaging the lacunae
are hypo auto fluorescent, lhe authors used Lhe term "RPH
hyperplasia and lacunae-4in describing this lesion; on care­
ful examination of the cases illustrated in Mgure 12.12.. iL
appears that all cases do not have excess pigment (Figure
12.12G-I.J and in some instances the hyperpigmenled
appearance may appear exaggerated from the contrast of
the hypopigmented center [ligure I2.12A and С )ч Several
of the eyes have 20/20 vision in spite of the center being
within the "lacunae/ implying that the RPE cells here are
intact but lightly pigmented (3:igure 12Л2С, D, K, and L).
lhe lesions are known lo progress minimally; choroidal
neovascularization ran occur similar to combined ham­
artoma. Overlying serous retinal detachmenl and fibrous
tissues have been seen, which are evidence suggesting lhaL
.1L least some of these are a milder version of combined
hamartoma, lhe dominant feature however, is the H leop­
ard spot appearance" of Lhe hyperpigmented RE’Ei wilh
its lacunae and scalloped m a r g i n s . V i s u a l acuities
range from 20/20 to 20/400 depending on the degree of
foveaI Ш’Е: atrophy or overlying retinal changes, including
sensory relinal detachment, cystoid macular edema, cho­
rioretinal folds, vilreomacular tradion, and choroidal neo-
vasculartzalion. Age at presentation is variable depending
E2. i 2 EJmlaleral retinal pigment epithelium (RPE>
dysgenesis (variant of combined hamartoma of the
R P E and retinal.
A and E3: This 17-War-old Caucasian j^iiI'h m acula has a
flat lesion W im Several patches u1 hyjtepijjruented, Lhan K P t
with finger-1i ke projections a I ih em af^ in. Is-I л n ris of normal-
appearing and hyperpigmenled К РЕ afe и я п belween I he?
hypomelanotic patches. К о overlying retinal vascular or
fibtotic a hnorma I i Li ris aft1 seen, yhe Was st'en pr^yjtstlsly at
age 10 with lhe lesion bul not photographed. Angiogram
shows w ind ow defecls corresponding Co lhe hypopigmented
RPE. Her visual acuity was 20/50 in this eye a r d 20/20 in Lhe
normal fellow eye.
t and D: This palienl has a laffte palch Ы hvpomelanoLic
RPt in lhe macula and 1; иperol ц т рога I quadrant with Lyp;-
caJ scalloped edge ol" hyperpigmpntaq PPL. Overlying mild
vascular lelan^i ectasia artd ffitfoils Iissue Iha I has ton Iracted
causing retinal folds is seen 1arrows I, hinting that lhe anom­
aly may nol be fimiled Iо lhe PPE. Visual acuity was 20/25,
LhuF- signifying hypopiwncnlml. EjliI intact PPE.
E and F: Anolher female patient with the lypical KPt
Eesion and clearly evident fihnovascular tissue in lh e reLi-
11a I suhslS^ftce (arrow) that shows vascular telangiectasia or*
anridg^pfy
G —|: Alm ost no EiyperpigmentaLFun seen at lE>e margins of
this lesion with a mild libiuvascular com ponenl and suhLle
relinal foEds 4G>. Fluorescein angiogram shows vascular
remodeling (arrows, L and Jj.
К and L: Another exam ple of a 47-year-old male w ith 20/20
vision and a flat, mostly lnypopigmented lesion w ilh lhe Lypi-
cal scallopEtd margins.
A. I!, b. I- К ;iгi■
:dL, L i i ' j r l ul Ur. K Rirhand McDtJhilc^ (J .ind 1>,
1с'Ui Nry-vol LJr. I-.iikkti-imi Cri££arcT; L .ммI I- cjuurlr^y ■11l>r. CInliijt
on Lhe severity of foveal involvement; often it is detec Led
as an incidental finding.
Sanderson Crizzard had a similar patient who was
reviewed by Gass in 1999 (personal communication:
figure 12.S2C and t>J. showing Lhe typical appearance,
including a mild vascular and librous component. W hy all
sporadic combined hamartomas and RE’F dysgenesis are
uni lateral and monofocal is unknown, bilateral and mul­
tifocal lesions have only been described in palients wltB
neurofibromatosis, (see Figure. 12.tlD-G and If-J)
REACTIVE HYPERPLASIAS OF THE
RETINAL PIGMENT EPITHELIUM
SIMULATING HAMARTOMAS AND
NEOPLASIAS
Л variety of stimuli are Capable of exciting lhe highly reac­
tive Ri-^H lo proliferate to farm mass lesions that may simu-
Eate RPli and uveat hш artCJtttatcius and neoplastic lesions
(E'igures 12.13 and l i l 4 j £ 1,fiA' 1 One of these stimuli
is recurrent and chronic focal choroiditis occurring al (he
site of chorioretinal scars in patients with the presumed
ocular histoplasmosis syndrome (E'igure 12.14F—L). The
Eesions may be pigmented or nonpigmenled and they
mniy be difficult to distinguish from choroidal melanomas
bionucroscopically, angiographically or ullrasonographi-
cnll y. ■ Hisiopathologicallyr some of tbe lesions in ay dem­
onstrate cytologic features suggestive of RPE neoplasia
(i'igure 12.1411-L). 'i'hese highly reactive lesions may be
locally destructive but л re apparently incapable of me Las-
tnisis. Histopalhologically the index of suspicion of reac­
tive hyperplasia should be high if lhe lesion arises within
or adjacent lo j chorioretinal scar, particularly in the juxla-
papiltary area. I'igure 12.1^3A -t demonstrates the unusual
development of mass lesions presumed to be reactive Rl'li
hyperplasia arising within congenital familial macular
coEobomata.
12. E3 Vitreo retinal traction causing lesions simulating
combined retinal pigmenl ep ith e liu m and retina;
h a m a rto m a (C R P E - K H ),
A—r : V itre o re tEn a l tra ction W as associated w ith a n e le v a te d
gray relinaE le s io n w ith d ita Le d retinal vessels s u rro u n d e d
Ejy a z o n e o f K P E d a r k e n in g in the in fe rio r fu n d u s d f Lh is.
b<jv w i IК bilateral X -!in k e d fo v e o m a c u la r *;■. n i kis- ' A a n d Ii..
A n g ic jjT d p h y s h o w e d d ila te d , d is to rte d , a n d p a rtly jbcqguded
retinal vessels ( Г . . O n e y a a r later lip id e x u d a te e x te n d e d in io
the m a c u la r A№ a f]? a n d L' i a n d there w a s in c re a se d v itre o u s
c o n d e n s a tio n a n d b a n d fo rm a tio n ti-..
G a n d H : This p a tie n t d e v e lo p e d loss o f vis io n a ss o c ia te d
w iLh v ilr e o m a c u la r Lraclion in Lhe left e y e . N o f e the lenlinj^
□f Lhe retina Езу л vitre o u s b a n d Ia rro w , C j . F o u r m o n th s later
Lhe ju x ta p a u illa rv re Lina w a s te n te d a n Le rio rly b y fu rth e r v il-
r e o js c o n d e n s a tio n a n d 1 r a d io n . N o t e the d a r k e n in g o f the
К PI: (a rro w , H ) lhal s u rro u n d *. tbe- m ass a n d c a u s e d il to s im ­
u la te L K P L - F t H .
I a n d | : Fo c a l v il neorel i па I |гл с й й Ц c a u s e d an e le v a te d p ig ­
m e n te d lesion assoc iflled w ilh d is to rtio n b f lb e relina l vessels
a n d a £ t$ y o p jre tin a l m e m b r a n e s ;:n u la lin ^ C J K K t -K H 11). F o u r
years I a I от lh e viln e o u s a n d pari o f lb e e p ire lin a l m e m b r a n e
larrovr1. Г s p o r rta ijjj^ Jtly d e p t h e d fro m the -retina.
[2.14 R e a c tiv e EiyperpEasia о I Lhe re tin a l p i g m e n t
e p i t h e l i u m ( RPE) si m u t a t i n g R P E h a m a r t o m a s a n d
choroidal m e la n o m a s .

A-E: Л nodule o f RKL hyperplasdel (artDWi£ A and В I devel­

d p e d wiLhin congenital m acular sLaphylomas of I hi & 25-year-
oJtl Woman. Visual acu ily was 20.400 bilaterally O ver
a period of several] vear* (tie К l-'E nodule in Ihe LefL eye
enlarged and a melanoma was suspected (Ск Angiography
revealed the presence о t bfoud vessels within the nod­
ule I a now, 1>i and lale Staining (EJ. Bilal eral m acula-г stairs
ntilud in eady childhood in the pa lit! i: I and her broLher ware
alLributed Lo toxoplasmosis. H ef j^rnndfalher had m acular
degeneration.
F and G : A small pigmented nodule (airuw, Ff developed un
l h e rii^hl optic disc d f l his fialienl w ilh multifocal c h u r i c u e L i -
nal and juxtapapJjj^Ey scars Lyplcal df the presumed ocular
hisloplasmoRii; syndrome (P Q H S j, Angiography showed dila­
tion o f l h e capillaries i n t h f i surface uf ltie nodule I d . and
lale sLaining.
H - L ; Tlii^ 64-year-old wom an w i L h hi liberal I’O H S devel­
oped л slowly enlarging mass on Ifie lefl oplic disc 'H i Lhal
far a period of 3 years was unassociaLed w ilh loss of visual
acuity,. before developm enl of an extension of lipid exu­
date inLo Lhe macula <Jk Because uf concern o f a m elanom a
a needle biopsy was dune. The results were equfvocal and
Lhe eye was enucfealed. Hislupathologically the Lumor was
compost'd of larj^e h уроЫдпл e г ted ИГЕ cells showing m ini­
mal miLolic activity IК and Lj. The Lumor was interpreted as a
low-yrade adenocarcinom a o f the KF’t by Shields eL a l.1" bul
in lhe aulhor's opinion represents reactive RPL hyperplasia.
i H - L Ггслп S h i c U l b Ш ! 1444. A r i iL 'N t . in M L - iJic .4 A i m e c i f f a r t . Л 31
rijjJils rubL'rvciiJ..
ADENOCARCINOMA (MALIGNANT
EPITHELIOMA) OF THE RETINAL
PIGMENT EPITHELIUM
Adenocarcinoma of Lhe RE1ti is an ejttremely rare tumor
Lind often Lhe diagnosis is made, after enuclealitin. linger
reviewed lhe literature in ]99614" and found 12 rases, the
majority of them in W o^EV e jl ( 10/ E 2 , often asso­
ciated u'itb uveitis,'inflammation (5 S% ), resistant Lo
plaque radiation or other treatment and resulting even­
tually in a painful blind eye. A few more cases have since
heen described, some de novo, and others arising from a
Gi IFtPE lesion.1^"1'1 H should be suspected in women with
a hyperpigmenled tuberous-appearing mass associated
with large feeder vessels, lipid exudation, and inflanmia-
tory signs (i:igure 12. ISA-G). The mass becomes highly
elevated, invades the sensory retina, and produces a pro­
gressive exudative retinal detachment (Hgure 12. IS A- F).
Gystoid macular edema, epiretinal gliosis, and vitre­
ous membranes are often seen over lime. Ultrasonogram
shows the elevated Eesion and associated retinal detach­
ment. Plaque radiotherapy, intravitreal steroids, photo­
dynamic therapy, vitrectomy, or other therapy does not
control lhe growth and Lhe eye becomes painful or phthis­
ical. Sections of (he enucleated eye show large sinusoidal
feeder vessels around a diffusely pigmented tumor (J'igure
12.1 SG and I I). Pathological examination reveals cords of
RPE cells on a basement membrane (L-'igure 12.1.ij), some
of which are anaplastic, where the adenoma has turned
I 2. \> Malignant epithelioma ot the retinal pigment
epithelium (RPE) (aden oca rei noma of the RPE).
Л -К: This- йО-уелг-oid asymptomalic was found lo
h a vr1 a raised p ij’ mcm Led Fnaisl in lh e Iftferotemporal periph­
ery w ith в feeding arteriole, surface relinal hemonhages.,
a n d 5urr4junding lipid exudates during a ro u tin e exam. Her
vision was 20/20 in each eye ГA'l. A year taler (he exuda­
tion h-nd increased and was associaL[!d w ith Kuhretinal fluid
(B). O ver the next 4 years Ltie lu m o f e n la rg e d w ilh surface
wrinkling, progres-yjve exudation, cysLoid nnacu!ar рН етл,
vitreuus cells, and fibrosis (tl and □). В scan reveals an
ovoid Lumor a n d adjacent relinal detachmenl E:i. During Lhe
subsequent 3 years she received various treatments includ­
in g lo p ic a l a nti suh-Tfjnonrs slerosds, ncmsLeroid a I aj^ents^
photodynam ic therapy, vitrectomy, and laser phulocoagu-
lalion. Overall., during this time the tumor progressed very
fitller bul the com plications progressed relentlessly. The eye
became painful and vision decreased to hand motions. She
underwent enucleation. Gross section re ve a ls a diffusely
pigmeiHed tumor Hind a d ja ce n L relinal deladunent. ^ote Lhe
large sinusoidal vessel н feeding Lhe Luinor aL ils base f(J anti
H:. HemaLoxylin and eosjn slain shown rows of R PE coils
ananged over its b a s e m e n t membrane Ц ). The inner R P E cells
show anaplas1ic feature* w ilh Lrger nuclei (K).
|{ 4 ju r tr * iy c jT L )r. lu r r y S t iiu k & L , i n d L Jr . C hto I S h ie ld * .)
into a malignant epithelioma (Ngure 12.iSK ). Shields
et al. have seen this in two African American women
where the affected eye became phthisical.Ifl E'o date, the
tumor is locally destructive and distant metastasis has not
been seen.
 38. FHiia'js A ZhiCh ZM. a E. el i . Caxea ta IweiiBrtN of tre 'ei na pt(r?r
References calhelL^ iiiairlialalewal'DiiEpcfjpcH;. ^Ihafmaiag^ l3B£:£fr&7£H14.'
1. Gies jDM. Faca tirqsrflsJ Dranslies cf te гяпз aдппет epte iп E-.e l9Ss:Si' -15. 39. £атж A. Wa'aes L. Нйта;аз-Си ills a E. el a.^n^nb:! Гцчгкср^ j tz relral r^ienl
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1*31: г Barchff з E^rfirca:; Nj d J M&j 1957:31 £.(£' -7.
3. £helds CL r/aitiDf/eti А "СТ el ai. Sol зт/ ctncenlal lupertraftyd Ts 'ei па ригам 45. N«j.ibthu aVH. Hr Oc<r-3Jal lts beft'^T :"iilal i;nsfe n APC yd ph5rcrf[>ecl laula
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angencal Tjpertrjclff al Stnai р с л ге т е р гГ е ш т Graces A d i O r Ы C tfth a n a - алсшаПйЕоит а"гта1геаяа1и ha frrilyvitti anTCEBTaiilfiam^dcniaid
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14 tar s JL. Сeasb. ML Ari Lru:u^ aae а! aten til f>pe hepitr-i те rslra pgptrlt 1973,6^7-30. '
cf-flTcl um. Aftf: CpTTal'tl 1975:94:193 '>1.. 52. thetis j^ Tse MCW. Ct>in lal crxps ис.^пйл' nf Ihs iami liRlipalhGlKj: cesjp^x
15. [h el& JA £hetas CL. SmgT 4). Acqjitil!j tfs aang !'ai ca jceila h^ptflrap7; Bis ■ra regol al i сж. ^jci OptithafiiKl 1 &7Ь.Й 1153-6.
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icJ th eta CL Rroln С, ВJTcicdc -Z.\r.2\. ^(сшущоепя- al oncea lal l^peJtncptifd Ts deenL'fihxJjin. Срт-fiiid 1^3:2E.72-4.
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This page mtentlonaSly left blank
Neoplastic Diseases of the Retina
RETINOBLASTOMA
Presenting signs of retinoblastoma include leukoco-
ria (a white pupil), strabismus, hyphema (blood in the
ante riot chamber), Vitreous hemorrhage, and, rarely, a
red painful eye (Figure: 13.01 A).' L3arents are usually the
first lo note a ''glared look,u "wandefttig eye," or "shiny"
appearance of the pupil. A prolonged Lime to diagnosis
advanced diseise, and exLraocuiar involvement are more
frequently observed in developing cou nines.J 'lhe diagno­
sis of retinoblastoma is made in ЭО'Мл of patients before 5
years of age.* in cases wilh a family history of retinoblas­
toma, the diagnosis may be made in the first few days of
Life al a screening examination. Although mosl patients
wilh retinoblastoma present as young, children, retino­
blastoma has been reported in palients as old as 60 years.1
Approximately 200 cases occur each year in the USA.'
Hi Iale гаI involvement occurs in 20-35% of cases. Second-
eye involvement is delayed in approximately 20-25с,й of
cases, lhe mean age of diagnosis is 13 months for those
wilh bilateral retinoblastoma versus a mean age of 24
months in those wilh unilateral retinoblastoma.0 In a
recently published study, the mean age-adjusted incidence
rate of retinoblastoma in lhe USA was 11.Я cases per m il­
lion children aged 0-4 years, similar to rates reported from
European countries.' Moreover, (he age-adiusled incidence
rate of retinoblastoma in the USA has remained stable for
the last 30 years.'
lietinoblasLomas are typically globular, while, usually
well-circumscribed tumors thal may arise anyw he re in
the fundus (figure 13.01 В and Cj. 'lhey may grow inward
toward the vitreous (endophytic] or ouiward (exophytic)
into the sub retinal space and may or may not be associ­
ated with ophthalmoscopic evidence of focal areas of
calcification [figure 13.01])/ Varying degrees of vascular­
ization of the tumor occur and this is usually seen best
with fluorescein angiography (Figure 13.0Ш, L, Ei, and
L ] ^ 11Telangiectasis of the retinal vessels on the surface of
13.01 Retinoblastoma.
A ' H e le i o ib r o m ia i rides, the p re s e n tin g m a n ife s to I io n o f
re tin o b la s to m a , in Ihe riijhl a y e o f chit intern.
B —F : La r^ e e x o p h y Lic re tin o b la s to m a . Molt? dilat-ed lo rLu o u s
retinal vessels th a l e xte n d d o w n inLo Ihe s u b s ta n c e c l Lhe
Lu m o r IB a n d l l j Lind a n g io g ra p h ic e v id e n c e o f sLu in in ^ I3>
a n d E). La r^ e b lo o d vessels la iro w s i w e re e v id e n l h ls lp p ^ th o -
lo y ic .illy пол г I ho su ila c e o f tb s tu m o r IF- .
C t - I : .4-1-Li ILi It* w h ile tu m o r seeds w e re e v id e n t a n lh e relinal
surface p o s te rio rly in this c h ild w i lh a p e rip h e ra lly lo c a te d
r e lin o b la s lo m a . T h e y s h o w e d n o a n g io g ra p h ic e v id e n c e o f
b lo o d vessels (лn o w s , H ' . N o le lh e n e c ro lic c e n te r o f Ihe
Lu m o r seeds (a rro w ) e v id e n t h l$ td p a lh o lo g ic a lly ■'!
I—I : S m a ll re Lin o b la s Lo m a o r re Lin o m a s h o w in g c a lc ific a tio n
u n o w , 1 1 in hi 4 -y e a r -o ld In d ia n c h ild w h o h a d e n u c le a Lio n
ol" his left e y e 1 m o n th b e fo re e x a m in a tio n . H is L o p a lh o lo jjic
e x a m in a tio n o f Lhat e y e re v e a le d re tin o b la s to m a w iLh in v a ­
sio n o l lh e o p lic n e rv e . H e w a s referred far tre a tm e n t o f
Ihis solitary lesion n o te d in ih e righl e y e . H e h a d л 6 -ye a r-
o ld b ro th e r w h o h a d a n e n u c le a tio n o f o n e e ye at b m o n th s
or a y .3. H is m o l h e r : F ig u re 1 3 -0 4 A - L i h a d а г е И п о т л .
Flu o re s c e in a n g io g ra p h y (JeveSffid a Line t ^ m lla f y n c lw o rk
w ith in a n d im m e d ia te ly s u rro u n d in g lh e tu m o r IК л n d L .
T h e re w n s e x te n s iv e leakage o f d y e fro m these vessels. rhjs
pa tioni d ie d o f w id e s p re a d m e la s l^ -is several m o n lh h later.
T h e clin ic a l a n :J a n a ® g ra p h ic a p fie a ra n c e o f I his s o lih u y
n o d u le is q u iLe s im ita r Lo Lhat o f retinal as I nocyLLc h a m a r lo -
m as a n d г ^ П п и т л .
exophylic tumors may occur. IJiomicroscopic and angio­
graphic evidence of communication of these dilated ves­
sels with blood vessels extending into lhe depth of the
tumor serves Lo differentiate retinoblastomas from pri­
mary retina] telangiectasis associated wilh underlying
exudative detachment (Coals' syndrome] [figure S3.01A-
]i).1Seeding of the tumor along the inner retinal surface
and into the vitreous occurs frequent!^ in advanced cases
[Figure 13.0K.-1]. tjitetision of retinoblastoma into lhe
anterior chamber may occur.1:
 As many as 80% of eyes con Lai mug relinohla&toma have
calcification demonstrable by ultrasonography or other
Lraiaging studies.1' Computed loinography (С Г) is superior
to magnetic resonance imaging (MRI) in detecting calcifi-
cafltpi.14 Uowt’veTr MRI is superior Lo С Г scan in defining
anatomic differences in pseudoglioma, particularly Соль'
disease, and in detecting exlraocular extension of the
tumor.1’ 115
Diffuse infiltrating retinoblastoma is an unusual type
of relinoblastoma (1.5% of cases}. ]( лгау simulate uve­
itis, is unassociated With formation of a discrete mass,
and may be accompanied by a pseudohypopyon (figure
L3.02).1■ ' l:: С Г and ultrasonography are of ! in i Led value
in lhe diagnosis of diffuse retinoblastoma. Other fea­
tures of this form of retinoblastoma are: older average age
of presentation [6 yeaть. compared Lo 13-24 months);
slight male predominance {6 4 % ); all reporLed cases have
heen unilateral and none has heen familial; and anterior-
chamber paracentesis is helpful in making the diagnosis. A
few patients with extensive involvemenL of the retina may
develop nrbUid vd.LJiLh lk.:.L is not necess^rih associated
with extraocular extension of the Limtor [figure 13,03}/
The differential diagnosis in patients With localized
white relinal tumors includes retinomas (figure 33.04)..
astrocytic hamartomas (see figure 13Л1), И яасат amis
granuloma {see figure 10.26)r intraocular teratoma and
com bilied pigmenl epithelial and relinal hamartomas (see
figure 12. N ).jV A rare intraocular teratoma is illustrated
in figure 13.0.511-К . Sacral teratomas are the most com­
mon newborn tumors ( i f .35 000): 75% occur in female
in fan t&. All teratomas seen at birth are benign, and ](>%
of those seen in older children are malignant, leratomas
arise from piuripotent cells from more than one germ
layer. In patients with large tumors and leukocoria, the dif­
ferential diagnosis includes relinal telangiectasis {(boats'
syndrome), Toxoaffia canfo. retinopathy of prematurity,
familial exudative vilreoretinopathy, pereistent hyperplas­
tic primary vitreous, retinal dysplasia, Lraumatic chorioreti­
nopathy- calcified intraocular abscess, and inconlinenlia
pigmenLi."'" Clinical features lhat suggest a diagnosis of
retinoblastoma are the absence of cataract and the relative
lack of in П а т т а Li on/'1Since surgery disseminates malig­
nant cells ouLside the eye and worsens Lhe prognosis for
survivatr intraocular surgeiyr including biopsy should only
be performed in exceptional cases when retinoblastoma
cannot be ruled out by other methods.
13.0^ D iffu s e in n itra tin g re tin o b la s to m a .
A - D : A 4 4 i-ve a r-o Jd b a y o n a v is io n tc nooning visit w a s
fo u n d lo h-ave h a n d m o tio n vis io n in the left e y e . tM e r n a l
л р р е а та п се re v e a le d lu u k o c o ria n f lh e lefl e y e at lh e lim e
ol initial ■м.!г(Ч'n in ц lA j. U ltra s o n o g ra p h y re v e a le d ir re g u E id y
Lh ic ke n e d fe lin a l d e la c h m e n l w ilh v ilre o u s ti& q i InLnsocular
m ass o r in tra o c u la r c a lc ific a tio n , features d iagnostic: o f
r e fin a b la g p m a w o re n-oL p r a w n I M a g n e tic re s o n a n c e
im a g in g c o n firm e d e n hkarnilrig Ih itk e n e d re lin a (С."!■. C ro s s
e x a m in a tio n o l the o n u t 'k ^ le d gldfce c o n firm e d find ing s o f
the im a g in g s tu d ie s. H F s lo p a lh o lo g y e s ta b lis h e d Lhe d ia g n o ­
sis ol' a d iffu se in filtra tin g re tin o b la s to m a I L » . P o o r p ro g n o s tic
fa t (on- fo r m etastasis such as c h a ro id a J in v a s io n , re tro la m r-
n a r o p lic n e rv e e x te n s io n , a n d uxLrascJera] exLen-sion w e re
a b s e n t.
f 3 .03 N e c r o lic ret in o b las t o m a .
A-D: A 13-monlh-oFd b o y p re se n led w ilh Je ll-s id e d orbital
ceil и li Lis. H e did noL hatffe past medical dr b c lila r hisLorv. a n d
family hislory was negative lor ocul.jr iLimor or olher jab nor­
malities. Examination of the lelt eye w as dilficull due Lo lid
g d e m a and c n n ju n c Liva l chomusis. A n te r io r exam in a tio n o f
Lhat eye revealed a diffusely hazy cornea, a fix e d m id -d rla Le d
pupil, arid brown-colored i rides. In-Lraocular pressure in Lhe
lefl eye was 2 2 m m H g (Aj. T h e v ie w of Lhe posterior p o le
in Ih e left «ye was unobtainable. Ё-ясап ullrasonography
revealed a large intraocular m ass extending from lh e o plic
disc w ilh a maximal heighl of 1 1 mm J J l . M u hi pi о sm il 11
hyperechagenic inLensilies w ere visible within (he m ass
Lind w e re pernisLenl al lo w g a in , co nsistent w ilh calcium
d e p o s itio n . Im a g in g w ilh magnetic resonance im a g in g con­
firmed left orbit p re - a n d postseplal edem a with an enhanc­
ing lesion along Ihe p o s te rio r aspect ol I h o left ^iobe (C l. T h e
palienl was slarleri on I epical prednisone and atropine, as
well as Oral prodn i no ne. This I regiment regimen lod Lo pa r­
tial improvcmunl of lhe orbital inllam m alion. E x a m in a tio n
under anesthesia confirmed I ha I Lhe righl E?ve w a s normal.
Li xa m iration of the lefl eye confirmed conjunctival ( Itcmo-
sis, corneal екЗсяпл, rubeosis, hyphema, and heterochromia.
A d d itio n a lly , fundus evalualron revealed v ilr e o u s hemor-
rhaye w ilh J J i ill-dufiiTud m ass al lht.f n^sal q u a d ra n t. Liespite
Lfio ruliooiis^ intraocular pnt^ssunj \vas 1 jf m m Jlg in Lhe lefl
eve. I!kt!Jv indicating я p r e p h th ja c a j slato. t;iven Lhe c lin i­
cal diagnosis of net. noli с r-elinofjlHisLoma, enuclealion ol" Ihe
loll eye was performed. Hislopalhology confirmed a relino-
^ilreal vascular Lind inflamrnaLcjry masu consisting ol" i'ibrin,
inflnmmalorv Cells; deLachod and dygerveraling reLina,
prominenL vascu'aLuTe, antJ a stlhiall amtHinl of necrosis, rdnd
calcificaLion 1DK Despite examinalion ot several cuts of Lhe
filube, I hem was i>r> evidence bl relinofilasltjma celli. It was
nbHiimed ihal the foLinoblasLom,! had undergone int"an:tior>
and was no longer detecLalile.
I rum j .slI fJ uv.l el ,bl., '' Wilh ptulrtilitlun.J
13.02
Retinoma/Retinocytoma
Kelinocyloma Is a benign variant of retinoblastoma, pre­
viously referred to as rctinoma, spontaneously regressed/
arrested retinoblastoma, And retinoblastoma group [J
(higure I3.04).35 J lhe diagnosis of retinocytoma is
based upon Lis characteristic features of homogeneous
translucent retinal mass, calcification, nonspecific reli­
nal pigment epi the] ini L [RPE) alteration, and chorii) reli­
nal atrophy^7 Neariy one-half of patients diagnosed with
retinocytoma have a tamily history of retlnoblasLoma. 15
Approximately SO^o of their offspring w ill develop retino-
bEastoma. Malignant transformation of a retinoma has
o ccurred.flu orescein angiography reveals evidence of
a vascular network within rellnonias and some evidence
of dye leakage (Figure 13.04D, li, El, and I).3' There
is often evidence of RPJi and choriocapil laris atrophy In
the area of the retinoma (E'igure ] 3.0415]. Anastomosis
between lhe relinal and choroidal vessels may occur.-1*
11istopaLhologically, in contrast lo retinoblastoma, reli­
noma/relinocvtoma is composed of well-differentiated.,
ben lgn-арреа ring mature relinal celEs without evidence of
necrosis or mitotic activity.5' Ophthalmoscopically retino-
mas appear identical lo so-called regressed retinoblastoma
following irradiation treatmenL (Figure ] J3.05}. ft has been
surges led that lhis portion of the tumor remaining after
treatment may be the result of a coexistent retinoma.’"-'
Retinoblastoma can be considered as familial or spo­
radic, bilateral or unilateral, and heritable or nonherliable,
ibus, a case may be unilateral sporadic, bilateral spo­
radic, unilateral familial, or bilateral familial. About two-
Lbirds of all cases are unilateral and one-third are bilateral.
Approximately 1044 of newly diagnosed retinoblastoma
1 3 . E) 4 R e t i n o m a / r e t En o c y t o т а ,
A —E : Th is a s y m p to m a tic 2 3 -y e a r-o ld m o th e r a i [he patlerrt
Illu strated in F ig u re 1 3 .1 F—L h a d three re tin o m a s ( А - C l . T h e
o n e in the right m a c u la h a d c lu b -s h a p e d c a lc ifie d o p a c itie s
i a rro w , Л . w ilh in LEie ^ o n e o f a W o p h ic ru lin a . A n g io g r a p h y
s h o w e d p e rfu s io n o f a n e tw o rV o f relin a l vessels a n d u n d e r­
ly in g Ear^e c h o ro id a l vessels in th e area o f Ihe lesion I D f .
There Was-s o m e s-Lnin-in^ o f I h o p e rip h e ry o f Ih e lesion :L i .
F: P ro b a b le heliftCrfna o r a ^ № i(y lic h a m a r lo m a in .in a s y m p ­
to m a tic 4 -y e a r -o ld c h ild w ith n o o th e r o c u la r a b n o r m a IiLies
a n d a negatiire fa m ily h is to r y
G - l : R e tin o m a w ith c a lc ific d liu n I a rro w , G } in a 2 1 -y e a r-
o ld a s y m p to m a tic m o th e r w h o h a d a c h ild w ith b ila te ra l
relirm EjlaH tom aK. N o t e lh e ,rfis h -fleshT lu m o r i ' O a n d Ihe rich
vahcuJar n e tw o rk a n d lo c a l li e d staining e v id e n t a n ^ io ^ ra p h -i-
c a lly ( H a n d I..
I К L d u I e I ) 111 =J r . t h r m . i r d li. D trfU
cases are familial and У0% are sporadic. All palients with
familial retinoblastoma are at risk of passing lhe
predisposition for lhe development of lhe lumor lo lheir
offspring From a genetic perspective, it is simpler to dis­
cuss retinoblastoma as fieri table or nonheritable. I leritable
cases [ones in which the predisposition lo lhe tumor can
be passed on lo the nexl generation} result from a primary
mutalion in the germ cells (sperm or egg. hence all rell-
nal cells in the individual have a first mulation) and sec­
ond mutalion(s) in retinal cells. Heritable cases include all
bilateral cases, all multifocal cases, all familial cases, and
at! cases in wbftch a second neoplasm developed. Aboul
15% of sporadic uniEateral cases (no family hisLoiy) are
also heritable.
 In about 10% of families, reduced peneLrance can be
seen in individuals (absence of retinoblastoma) who are
determined to be RBI mutation carriers, either through
molecular diagnosis or obligate carrier status in a family.
Mechanisms of reduced penetrance and variable expressiv­
ity include mutations that lead to reduced expression of
retinoblastoma protein expression or production of par-
Lially inactive protein."'"1'
Hie human retinoblastoma susceptibility gene (S S l)
was sequenced in allowing for development of
molecular techniques for mutation detection and diag­
nosis. is located on chromosome 33 region q]j5-
Et is relatively large, with 180 kilobases and 27
exons. А п л lysis, of a large number of germ line mutations
in patients With hereditary retinoblastoma has revealed
Lhal about 15% are large deletions, of which ^5-6%
are cyto genetically detectable, 26% small-length altera­
tions including small insertions and deletions, and 42?□
base substitutions. 1 lift I mutation analysis is appropri­
ate in any case of retinoblastoma when the results will
affect future treatment or surveillance. ■ ' tn patients with a
known or suspected family history1of retinoblastoma. f?BJ
analysis will detecL a mutation in ^O^ii of families. ]f tfJi/
mutation has been identified in a family, then the indi­
vidual is tested for the specific known. family mutation.
In this manner, unaffected at-risk children with a family
history of hereditary retinoblastoma can undergo predic­
tive testing. Prenatal and preimplantation genetic diagno­
ses are also available when act mutation is known in
a parent or sibLin^.'' -l bilateral tumors in the setting of a
negative family history aEso indicate a high probability of
a germ line ЯШ mutation (^90%) and therefore test­
ing is recommended. In sporadic cases, it is recommended
that both peripheral blood and tumor tissue (if available)
should be analysed. In all situations, a positive result
clearly establishes a diagnosis of hereditary retinoblastoma
but a n e g a tiv e result does not rule it out completely.
13 ,0 5 R e t i n o n W r e t in o c y t o m a ,
A —D : A 3 2 -y e a r-o ld C a u c a s ia n m a r w as e x a m in e d b e c a u s e
his I w o c h ild re n w e re d ia g n o s e d w ilh b ila te ra l m u ltifo c a l
n e lin o b la s lo m a b e fo re Ihe age b f 1 ■A J . H e re p o rte d a h is to ry
□I fta m b ly o p ia " in Lhe right e ye w it h a vis u a l a c u ity o f 2 0 /4 0 .
D ila te d fu n d o s c o p y s h o w e d tw o c irc u m s c rib e d c h o rio re tr-
n.al a tro p h ic lesions in the te m p o ra l re g io n o f lb e m a c u la 1EJJ.
N o n s p e c ific retinal p ig m e n t e p ith e liu m (R P E ) c h a n g e o f Lhe
m arg in s a n d m in im a l intrinsic c a lc ific a Lio n w e re e v id e n t.
Flu o re s c e in a n g io g ra m s h o w e d transm ission defects in d ic a ­
tive ol" Fif'3: and c h o ro id a l a tro p h y (С )- O p t ic a l c o h e re n c e
to m o g ra p h y c o n firm e d m a rk e d retinal a tro p h y w ilb in Lhe
loF-ions ( D j . N o retinal lu m tw w a s id e n tifie d .
T h e p a tie n l, his s e c o n d d a u g h te r, a n d h e r b io lo g ic a l
m o th e r u n d e rw e n t g e n e tic testin g . A h e te r o zy g o u s С bo С
su b stilu Lion in lh e fin a l base f>osition o f e x o n 1 3 o f Lhe RHI
g e n e 1 C .1 5 6 0 G —*(I iV £ > 5 4 D f w a s id e n tifie d in th e p a tie n t
a n d his d a u g h te r o n s e q u e n c e a n a ly s is o f p e rip h e ra l b lo n d .
This m unition- < a и sod m is s p lic in y a n d o u l-o t-fr a m e s k ip p in g
o f e x o n 19 lh a l resu llod in a s u b s e q u e n t le rm m a iic m c o d o n ,
a n d u n n la b le rn h JN A w ilh su b se fld £ n t re d u c tio n or lbe re tin o ­
b la sto m a p ro te in . Th e m o th e r d id not h a v e the m u ta L io n .
Teratoma simulating retinoblastoma.
E —K :T w o g ra y e le v a te d tu m o rs in the rig h t fu n d u s o f this
2 -m o n th -o ld jjirl b o rn at i 2 w e e k s b y cesarean secLion.
N o L e lh e a b s e n c e o f la r^ e fe e d e r vessels; d ip p in g in k) Lhe
Lu m o r {E j. V is u a l a c u ily w a s n o lig h t p e r c e p tio n ; tbe left e ye
was n o r m a l. Flu o re s c e in a n g io g ra p h y s h o w e d in cre a se d
vascula riLy w ilh in th e fHass a n d I ale h y p e rflu o ru s c e n c e ( F :.
T b e lu m o is g re w in si^e o v e r Ihe n e xl 2 m o n lh s r a n d subse­
q u e n tly d e v e lo p e d a total retinal d e La c h m e n l | C ) , n e o v a s c u -
b iriza lio n o f lb e iris, a n d b uphLhalm < *s. E n u c le a tio n (F ll a n d
b is lo lo g y re v e a le d c a rtila g e , m u s c le , re s p ira to ry e p iLh e ffu m ,
g la n d u la r, anrl b rain tissue consislenL w iLfi a LeraLom a (I a n d
f). T h e c h ild h a d b e e n d e liv e re d b y e le c tiv e cesarean s e c tio n
aL 32 w e e k s for a sacra] LeraLom a :K 'h a t w as o p e ra te d u p o n
s o o n after b ir lh .
; t - k . K n u r l ^ y >}| U r . I j . i v n J Д к И л г л Ю П ; L an d к ita u I ru m V f t Jr r t Jlfl,
L i\\Tfi к и I .. the Bfcttnul All,is. ^PiuritliTi 2 (1 1 0 , 9 7 i H J . 7 r J 2 0 . : i . 5 2 0 - 4 r
®
 In recent years there has been a trend away front enu­
cleation and from externa I-beam radiotherapy with the
increasing use of alternative globe-conserving methods of
treatment, including laser photocoagulalion, cryotherapy,
Lranspupillaiy ihermotberapy, plaque radiotherapy, and
chemotherapy.4" n': Laser photocoagulalion or transpu-
pLllaiy thermotberapy is used lo treat very itmall tumors
located posterior to the equator.,|■ ■‘|,' At' Cryotherapy is
used to treat very small tumors located anterior lo the
equator.11" ITanspupillary thermotherapy may be used
for small tumors eilher primarily or in con junction with
chemotherapy.'1L"ll:-'|:' Plaque radiotherapy is highly effec­
tive in treating medium-sized tumors either as primary
treatment or as secondary treatment for recurrent tumors
(figure I 3.06J _‘Jl J ' bxtern al-beam radiotherapy is less
frequently used for large and multiple tumors associ­
ated with vitreous se e d in g .Lm u c le a tio u continues Lo
he the main therapeutic option for advanced uni lateral
retinoblastoma/1 1 B : 4 o t e d ra m a tic re d u c tio n in lu m o r HJ^e. S u b s e q u e n tly ,
bince the 1990s chemoreduclion has been increas­
i n g used for the management of retinoblastoma Lo
avoid externa I-beam radiotherapy or enucleation.'" ''
Chemotherapy is delivered intravenously to reduce the
volume of intraocular retinoblastoma to make it amena­
ble to focal therapy, such as cryotherapy therm olherapy,
or braehytherapy (Kigure ] J3.07J . Six-cycle chemoreduc­
tion using three agents (vincristiner etoposide. and carbo-
platin) is generally prescribed." " Based on the available
(noncomparalive series) data it can be concluded (hat
chemoreduclion combined with adjuvant focal therapy
offers about 50-100^ probability of avoiding enucleation
or external -beam radiotherapy depending upon the sever­
ity of disease at initial presentation.5^*® It must be real­
ized that chemoreduclion is not without its problems.
! 1.0i'i Ret inobla stoma treated wi th iodine episcle га I
plaque.
A h -m o n lh -o k f girl w ith a ra m ilia ] u n ib te n a ] re tm c b la s lo m a
ol Ihe m a c u la r re g io n . T h e tu m o r w a s 9 X 9 m m in basal
d im e fis rfir a n d w a s 4 m m in tiei$}hl.
Л : A s s o c ia te d HuEinetina] flu id a n d s e e d in g iv ilre o u s a n d s u b -
relinal ware? a b s e n l:. The tu m o r W as b e a je tl w lLh io d ir> u -12 5 -
nntebfed e p i^ 'le r a l p la q u e .
B : R m d u s a p p e a ra n c e 4 w « jk s i later. The I и т о г has
re m a in e d regressed o y e r a p e rio d o f 3 years-.
\ J,D7 Retinoblastoma treated wilh systemic
chemotherapy.
A: A b-month-oid ^ irl pjesenLt4J W ith bflaSftal reliiM)bl<LS1oma
(group D, right eye; group Ef left eyej. She was treated witb
chemoreducfion and sub-Tenon carbopiatin (cycles 2 —4i.
She aIsa receJVaJ adjuvanl focal theram (crvutherapy and
tra nspupi Mary t hermothera pyI.
then? w as ret u rre n c e cU lh e m a c u la r lu m u r , w h ic h ["ailed lo
re s p o n d Lo io d in e -1 2 5 p la q u e . T h e left e y e w a s e v e n tu a lly
e n u c le a te d .
Recurrence of the neoplasm while on chemotherapy has
been observed. Immediate com plications related lo
transient hone marrow suppression requiring hospital
admissions and intravenous antibiotics with consequent
delay in examinations under anesthesia are frequent. Risk
of late complications such as drug-induced leukemia can­
not yet be excluded.04' it is recommended that chemo­
reduclion therapy for retinoblastoma should only be
offered at a specialist center.
 International group classification of ret inobles Ю та, a
newer system of classification of retinoblastoma, is most
suited for lhe present-day management of retinoblas­
toma compared Lo lhe traditional Keese-Ellsworlh classi-
fieation.''^'* Eyes are classified according lo the extent of
disease and dissemination of intraocular tumor defined
by the most advanced tumor in each eye. Moreover, the
international group classification of retinoblastoma forms
the basis of Children Oncology Croup trials currently
underway.""
More recently, there is a trend Lowards superselective
delivery of chemotherapy (melphalan) via cannula Lion of
the ophthalmic artery 6' i he aim of such an approach is
to avoid Lhe systemic complications and to achieve higher
drug levels within ihe vitreous cavity. Although the initial
results are encouraging, such treatments sliouEd only he
conducted within a framework of a clinical trial in a spe­
cialised center {Hgure I3.0S).I"■, ЧЪе procedure involves
three 1-weekly injections of I cc/5mg melphalan (diluted
En 30 ml of normal saline), an alkylaiittg agent, directly
into the ophthalmic artery via selective percutaneous calh-
eterization via the femoral artery. An approximately 4 5 0 - f i m
(] .5-1 1 french)-size catheter is used; an arteriogram is firsL
performed by injecting contrast into lhe ophthalmic artery
Lo ensure good blood supply to the eye, following which
[he medication is infused (figure ]3.0SC-E], Since the drug
is injected into the arterial supply of the Lumor, a very small
dose of one chemotherapeutic agent has proven sufficient
lhe procedure is done by skilled inteiventional neurora­
diologists and has a learning curve, lhe drug is injected in
a pulsatile fashion so as to deliver the drug uniformly. In
bilateral cases [figure 13.0SC-JJ. after the chemotherapy
is infused through one ophthalmic artery, lhe catheter is
withdrawn into the aorta and threaded into lhe opposite
internal carotid artery and on to the ophthalmic artery and
delivered to the second eye. Complications outside the dif­
ficulties with catheterization include complete vascular
obstruction of the arterial supply leading to total blind­
ness if the catheter is wedged tightly into the lumen of the
ophthalmic artery, ih e procedure is successfully performed
at the Memorial Sloan Kettering by Dt. David Abramson
and his team (USA) and in some centers in Europe.11" " '0
About й % of patients with heritable retinoblastoma
may develop an associated pineal oh lasloma, a tumor
that is identical lo retinoblastoma. 1 ihis association of
mid line intracranial pineal tumors and Suprasellar/ para-
selEar neuroblastic tumors with bilateral retinoblastoma
has been termed trilateral retinoblastoma. 2 Lin like other
second tumors mentioned below, pinealoblastoma usu­
ally occurs during the first 4 years of life." Prospective
screeiiing by periodic neuroimaging is generally recom­
mended. ' The possibility flf pinealoblastoma should be
included in the genetic counseling of patients with heredi­
tary retinoblastoma Newer evidence suggests that recent
treatment methods of systemic chemotherapy/'1A total of
35% of trilateral retinoblastoma patients have bilateral ret­
inoblastomas and in mosl cases the disease is fatal Most
1 3 .0 8 In tra -a rte ria l c h e m o th e r a p y fo r r e tin o b la s to m a ,
A - J : t h is 1 0 -m o n t h -o ld i^irl, o n e o f а n o n idem ILcall sel o f
tw in s w ith U n ila te ra l re tin o b ia K lo m a , h a d л la rg e m is s w ilh
a Iota I re lin a l d e la c lim e n t a n d fi flat e le c tro re lin o ^ ra m ( E R G }
IA fin d E f . S h e re c e iv e d 1 c c ol m e lp h a la n En tra -a rie ria H y
o n c e a w e e k fo r 3 w e e k s . T h e c a th e te r lh a l is 45 -O jim in
d ia m e te r is th re a d e d Lip lh e irrLerna] c ,iro 1id grlery in to the
o p h lb a lm ic Artery CI—L i. V k'lp h -a la n is in je c te d in a p u ls e d
m a n n e r so as no1 to o b stru c t lh e blood flo w lK ro u g h Ihe
artery. T h e retinal d e ta c h m e n t d is a p p e a re d , the tu m o r
s h o w e d c o tta g e -c h e e s e ty p e of reg ression, a n d 6 0 % of' h e r
E K C a m p litu d e s re tu rn e d ■F ).
G —|: A n o th e r c h ild w ith hi lateral m u ltip le tu m o rs ( C a n d H !■
н Ы т -s c o m p le te regression il a n d |..
M e d и I [ o e p i t h e lro т а ,
К : A J -y t 'a r -o ld w h ile Ljir] w a s e v a lu a te d fo r a w h ite pupillary
re fle x in h e r right еукз. E x a m in a tio n re ve a le d .1 p ig m e n te d c il­
ia ry b o d y m ass With a f iljro v a s c u I nr m e m b r a n e s u rro u n d in g
the lens. F o llo w in g initial resecLion^ the e ye w a s e n u c le a te d
b ecau se o f tu m o r ret u rre n c e .
| A - | , r j j u r l L ' i - y u f U r . I J . w i l I . 'i.l.ir ,L m .- ,u n : H , . i l s o 1 г и т Л Ь м п и п l L .n J .'1 ''
■ J l'i! D j Л л и г н - л п M u liL .h l A iK J c ia l м п . Л И k fflh t r te tt V e d . A. h C.J, H . I
ifjd 1
I. , M ; M ; j m Y . i n r i u ^ i . L Л Х ' г г Н ) с с Г I n . ' K l T :п.ь1 A l I . l \ & n u r tc ld t f Л ) | ( ' .
l) 7 { U ) - 7 a 2 0 - 3 ^ 2 ( ) - 4 , p. f 1 2; К tm rri S h ie ld s c L a \.v -■■ 2 1 Ш A r w r iu iin
M c .tllL .h l A s K 5 L J.L lM ]n . A l l г H '- i L T V U d . ■
patients present xvilh symptoms of increased intracranial
pressure caused bv obstructive hydrocephalus.
An important aspect concerns the development of unre­
lated cancers in survivors of bilateral or heritable retino­
blastoma. The mean latency period for the appearance of
the second malignant neoplasm (SM N J is approximately
13 yeais.75j7& There is a 5% chance of developing SMN
during the first 10 years of follow-up, 18% during Lhe first
20 years., and 26% within 30 years.7 lhe 30-year cumu­
lative incidence of SMN is about 3S% for those palients
who receive radiation therapy [extern aI-beam therapy) as
compared to an incidence rate of 6% for those palients
who do not/6 Osteogenic sarcoma, often involving the
femur.. is most common, but other tumors such as cuta­
neous malignant melanotnar spindle cell sarcomar chon­
drosarcoma, rhabdomyosarcoma, neuroblastoma, glioma,
leukemia, sebaceous cell carcinoma, squamous cell carci­
noma. and lung and bladder carcittomas as 5MN have also
been recognized. ■п,й0
Several studies have evaluated histopathologic prognos­
tic factors for metastasis, including choroidal, oplic nerve,
and exLrascleral extension.1'1 Choroidal involvement by
the retinoblastoma is a risk for metastasis, especially if it
is associated with any degree of optic nerve involvement.1 ^-1
Mori alily increases with increasing extent of optic nerve
involvement.: However, it is generally agreed thal prelami-
nar involvement of the optic nerve does not increase the
risk of nietaslasis.:::' ihe impact of laminar involvement
on metastasis is debatable. Retro!aminar involvement is
a poor prognostic factor and optic nerve involvement by
retinoblastoma cells up lo the line of transection predicts
lhe worst prognosis.-3
Jin
 ]( must be realized that retinoblastoma-related mor­ 14.01? Ret inat ast rocy t iс ha ma rto ma assoc la led wit h
tality could be due to one of three distinct causes: ( t ) In be ro us sclerosis,.
metastasesj [2) trilateral retinoblastoma: and (3) S.Ml'J. A —C : M u ltip le a stro cytic h a m a rto m a s , o l (Lie o p tic п е г v s h e a d
Metastases in retinoblastoma usually occur within I year ,i n l I relin a in a 3 5 -y e a r -o ld w o m a n w iLh luEjerou;- sclerosis
□f diagnosis. Metastatic retinoblastoma is observed infre­ (A . She h a d a life lo n g h is lo rv o f g e n e ra lize d s e izu re s . Stie
quently in the LISA6 and other developed nations.'14' ' h a d five m e n ia lly re ta rd e d c h ild r e n . E x a m in a tio n ttfV e ^ie d
Howeve^ metastasis continue lo be a challenge in devel­ s e b a c e o u t a d e n o m a A n d s u b u n g u a l fib fo m a S o f lh e finders
rind Joes U -igure Ю Д з В ) . M u ltip le c n d o p h y lic asLrocyLic
oping nations.'' '9J Iherefore, bone scans, lumbar punc­
h ,im a N o m a s o f lh e rail inn wurcL presenL in the lull fu n d u s . Th e
ture, and bone marrow aspirations at initial presentation
lesions w e re e le v a te d , g lo b u la r , a n d s e m itra n s lu c e n L. R e tin a l
are generally not performed in the U S A . 1' * If there Es no vessels c o u ld b e seen w ith in s o m e o f these tu m o rs . Several
metaslistic disease wilhin ^ yc.-is <i\ retinoblastoma diag­ □I tEie tu m e fa c tio n s s h o w e d e v id e n c e o f e a rly c a lc ific a tio n
nosis, lhe child ts usually considered cured.H l Meta&Lases [a rro w , A . Л n j^ o g ra p Eiy re v e a le d a c M i l n r y n e tw o rk w ith in
usually involve the central nervous system (CNS), bones, lh e h a lfta rltim a s '.B a n d О . The se c a p illa rie s w ent' p e rm e ftijffi
and bone m a r r o w , T h e prognosis of metaslatic retino­ to flu orescein d y e , a n d th e m w h s e v id e n c e o f d iffu s io n o f the
d ye in lo Lhe vitre o u s - t j .
blastoma is poor, wiLh death usually occurring wilhin G
D - F : A pa n ly c a lc ifie d cystic a s lro c y fic h a m a rto m a in a
months/4-'4 In the USA. over a period of 30 years (1975-
У -y e a r-o ld L|irl w ith luEierous scle rosis. S h e h a d a history o f
2004 the 3-year observed actuarial survival rate increased s e izu re s Liu I w a s n o t m e n ia lly rtilardsMi N o t e Lhe m u lb e rr y -
from 92.3% { I975-19S4] lo 96.5% (1995-2004). i kt' iic .i' :i| iviiul'ii'.rtiun i:hin 11к- Ian.1." (\sU< I i - . 1vvh:■
sm alle r h a m a rto m a s W e f t p r e ^ n l w ith in lb e o p lir n e rv e
MEDULLOEPITHELEOMA h e a d [a rro w ) a n d in fe rio r to th e p a p itlo m a c u la r b u n d le .
F-luorescein a n ^ io ^ a p h y d e m o n s Lra Jo d d ila tio n o f Lhe c a p il­
Intraocular medulloepilhelioma is an embryonal neo­ la ry n e tw o rk a n d s ta in in g w ilh in th e se tu m o rs IE a n d f\.
G —I: L a r g e a stro cytic h a m a rto m a o l the left m a c u la o f a n
plasm of the ciliary epithelium. It may Contain cartilage;
3 -y e a r-o ld b o y w ith tu b e ro u s sclerosis, h e h a d se b a ce o u s
skeletal jnuscle. and brain tissue (teratoid medulloepithe-
a d e n o m a a n d a large fib ro m a o f the I e L'( lo w e r lid (Cl.
lioma).'11''"' MedulEoepithelioma typically presents during
[he first decade of life with poor visionr pain, leuk оcu­
ria, □rid iris vascularization associated wilh a mass or cyst
appearing behind the pup ilia ry area [figure 13.0&K).’ ''
Children wilh neovascularization of the iris of unknown
cause should be evaluated lo exclude underlying lhal are more evident angiographicaEly than ophthalmo-
meduHoepilhelioma.'''' IJecenLly, an association wilh pleu- scopically (figures 33.0911 and C, and 13.1!Lan d f). 'lhe
ropulmonary blastoma has been reported.11"1Therapeutic tumor's blood vessels are usually permeable to fluorescein.
options include local excision or enuclealion depend­ In addition to nodular reLinal tumors, Hal or slightly ele­
ing upon the size,, location, and secondarv effects of the vated, while, circular or oval aslrocytic hamartomas of the
tum or.'^7'jQ] inner retinal layers are common (figure 13.09D). 'Jhese ses­
sile tumors show less Lendency to undergo calcific degen­
ASTROCYTIC HAMARTOMAS eration. In general, retinal astrocytic hamartomas show
minimal evidence of growth and no treatment is indicated.
Retinal and optic disc astrocytic hamartomas may occur Occasionally, however, particularly in younger individuals,
as a solitaiy finding in normal patienls.. in patients with progressive enlargement and calcification of these tumors
dominantly inherited tuberous sclerosis complex |’'fSC) may be demonstrated [figure 13. №G to J, 13. il l-L)."*
(Etournevilie's disease), or rarely, in patients wilh neu­ Visual Loss may be caused by Lumor growth, vitreous hem­
rofib ro malosis (von Fieckli ngh ausen 's disease).9 m ' 1J 1 orrhage. or intraretinal and subretinal exudation (figure
lhe intraocular lumors are typically globular, white. Well- L3.!2L}-E-y°-'lCM l,l,]JU,JJti-|ift The exudative complications
circumscribed, elevated lesions arising from the inner sur­ of astrocytic hamartomas can be self-1imited, and cases
face of the retina or optic nerve head (Figures 13.09-13.11). of spontaneous resolution wilhin a few weeks have been
Multiple lesions are common in patients with 'ESC (figure observed (fig. 13.1 OK to N }' " " ',u; however, some cases are
13.09A-F). tiarly in life the tumors may be semilranslu­ persistent, progressive, and vision-threalening. and for these
cent, free of calcification, and mistaken for retinoblas­ cases various treatments have been attempted, including
toma ( E:igures S3.09A and D, and l | . ШР} laser photocoagu lation (E-'igure 13.12t>—b),'"' brachyther­
In infants and children they may occasionally arise where apy. transpupillary thermotherapy, and endoresection.l M
earlier no lesion was present. Later in life they assume a More aggressive cases exhibiting progressive growth, Lumor
more densely while color and mniy develop multiple nodu­ seeding and neovascular glaucoma have been managed by
lar areas of calcification, taking on a mulberry appearance enucleation.1' 1 Recently, photodynamic therapy using Lhe
(E'igures 13Л9Д and D, 13.1Of, and 13.11A). Clear cystic photosensitizing dye verteporfin (Visudyne) has been used
spaces may be present within tbe tumor (Figure L3.09D). in the treatment of a few cases of exudative astrocytic ham­
'lhe tumors may show varying degrees of vascularization artomas, with encouraging results ( figure 13.13).-11■ ■''
 In in n it the rapid growth and necrosis may be etsLe-
taken for a nonpigmenled melanoma (figure ] 3 . J I J —
1_^пб,127.12й,ив-иа [n рдЦ^шь the highly vascular
component of lhe lain or may simulate a retinal angioma
[Figures 1&1DG-J, 13.11 ti-S and 13.12Л-С).15* In lhe
case of spontaneous necrosis astrocytomas may simulate
necrotizing retinochoroiditis.'Ji The fossilised mulberry
tumors involving the oplic nerve head should be dis­
tinguished from hyaline bodies of the oplic nerve head.
Ihese latter are calcified masses of extracellular material
unrelated lo aslrocylic hamartomas. When calcified astro­
cytic hamartomas of the optic disc are small, they may be
difficult or impossible Lo distinguish from hyaline bod-
ieit106 Demonstration of growth of these small lesions in
patients with retinilis pigmentosa has suggested that these
Lesions in palients wilh retinitis pigmentosa are astrocytic
hamartomas.I!'- 11" 11' Itetinal lelatigiecLasis, relinitis pro-
liferans, and retinal exudation developed in one eye of
a patienl with familial '["ЬС bul no evidence of a retinal
U«Ti
astrocytoma.
13.E11 Ret i nat ast r(icyt i с ha т а rio т а associaLed \vi th
In be ro us sclerosis,.
A - D : S e b a c e ftU s a d e n o m a o l [h e nose a n il ch e e ks a n d a
ьЫ Нпту h a m a rto m a ul Ihe fo re h e a d A I. iu L ju n g u a l fib ro m a
(a rro w , E3>. 5ku 11 X -ra y film o f p a tie n t s h o w n in (A t s h o w e d
m u ltip ly c a lc ifie d a stro c ytic h a m a rto m a s (a rro w s ) ch a ra cteris­
tic o f lu b e ru u s sclerosis (C t. E n h a n c e d c o m p u te d to m o g ra p h y
scan s h o w e d m u ltjp lo a stro cytic h a rn a rtq m a ti in lhe1 p a r a № l>
L r k u la * system o f a pa Lien I w ith CubeitHJ.H s d № H i i :D l .
E a n d F: P I » lo m fc rogr-aph o l ca lcifie d a s t r o c w c h a m a rto m a
ii lhe d-plit : -iм. a n d .i-cJj;чс.ч'п1 relina ot" л E 7 -ye ar-o ld h o y w ilh
sebaceous a d e n o m a . T h e c a lc ifie d central p o rtio n o f the lu m o r
was lost in s e c tio n in g HE j. E n d o p h y tic n o n c a k ifie d astrocytic
h a m a rto m a o f the peripheral retina o f I h e -same pa tienl in b (F^.
Growth ol" astrocytic hamartoma
G-J: In 1 9 7 0 . this В year o ld m ale palienl w a s e v a Jte te d al
W ilm c r w ilh a ca lcified aslrocylic h a m a rto m a in lhe ra^hl e ye
iC i a n d 4 lesions m lh e left e y e consisting o f 2 a tto p h k p a k h e s
a b o v e I he ST a rc a d e , I ca lcified and a n o llie r n o n ca lcifie d
h a m a rto m a a lo n g the I T a rca d e (H ) . T h e o p tic n erve Was s w o l­
len w ith bkirned margiYts suggesting pjcssence o f а Ь п о т т а Г t:s-
SLie w ith in il* substance. H e pn ise nled lo V a n d e rb ill in
w ilh a vitreous Iw m o rrh a j’ e in Jn is- Heft e y e fro m a large p a rtly
ca lcified a n d partly fiEwous ElprrlaHom a thal had gTow n ( r a n the
optic disc I|j. K o L e the p re vio u s ly n o n ca lcifie d Lu m or inferior lo
the o p lic disc w a s n o w ca lcifie d fa rra w f. Th e ca lcified astrocy­
tom a in the righL e y e was u n ch a n g e d ilj. T h e lefl e y e n e e d e d л
vitre c to m y a year laler few further vilreou s h e m o rrh a g e .
Spontaneous regression of astrocytic hamartoma
K - N : This 1 1 y e a r o ld b a y w ith k n o w n history o f luberous scle­
rosis presented w ith an inferior scotom a in his ri^ht Fiye. H e w a s
fo u n d to h a ve a c irc u m s c rib 'd gelalinous a p p e a rin g vascular
Ees-ian superonasal lo the disc associated w ith [*p id a n d b lo o d
i K i. Fluorescein a n g io g ra m s h o w e d vascu la rily o f lhe 3etion
w ith o u l e v id e n c e o f retinal n o n p e rfu s io n e ls e w h e re (L|l T h e
lersion I r e ^ n Lo regress s p o n ta n e o u s !у 2 m onths ialer w ilh f^ a d -
ual resol ul ion o f lhe sc o to m a . B y 4 m o nths lh e lip id , b lo o d and
vascularily of Llw lesion had repressed c o n s id e ra b ly i.M a n d N ).
It ;md I-, ■г11“ii ijm ii m i H il -mkI lY.tlih - - K -N , Dr. Alf-urtiTi
 llislopathologjcally, these tumors are typically com­
posed of spindle-shaped fibrous some of which
are elongated and contain small oval nucleoli [E'igures
13.1 t,lb And 13. ML). Other tumors are composed of large.,
bizarre- pleomorphic aslro(r>rLic cells, Lhat ьл at least one
case showed ullrastruclural and histochemical similarities
Lo Muller cells.1 ' Cystic areas poiitairiing serous exudate
and blood, as welt as areas of calcified degeneration, may
be present, Some of these tumors may be of Muller cell
orig in ."11
Ketinal acbromic patches have also been observed
in published series, ranging from 8 % to 39fl/ii of ISC
patients. и lfl1 Some authors have described these lesions
as diffusely hypopignteuled.. Wfalle others have noted them
to be surrounded by some degree of pigment proliferation
(b'i^ure 13.!4).1J 5,-11' Clinically, these lesions bear a strik­
ing resemblance lo the solitary-type hypomelanotic nevi
described by Dr. Cass. "" W hile retinal achromic patches
appear in increased frequency1 in individuals wilh ISC.
the underlying mechanism explaining their existence is
unknown.
! i. E1 Retinal astrocytic hamartomas not associated
with tuberous sclerosis,
Л - t : La rg e c<dciLied e x o p h y lic a s lro c y lic h a m Lirio m a o f
the re lin k in a 1 5 -y e a r -o ld b o y w ith o u t o th e r e v id e n c e o f
jj^betdtifc нс1егоча ;A l . He; g a v t1 Lin E -y e a r hrslorv o f d e fe c ­
tive vis io n in lh e ri^hl e y e fitil noLed w h ile firin g a g u n . Th e
fa m ily h isto ry a n d pasl m e d ical history w e re n e g a liv e . V isu a l
a c u ity in (he a ffe c te d e y e was 2 0 /3 0 0 . A n q io i’ m p h v 111 a n d
C!'l reveLT.[t4J a n e x le n s iv e № i l l a r y n e tw o jk that e x le n d e d
d o w n into the и т о г . T h e re w h s leakage o f d y e fro m I his n e t­
w o rk a n d p tin iin ji a t d ye w ilh in lhe c y s lk агеав o f :h e EUm Or
fa rro w , C ) .
D - F : C y s tic a s l r o c y t i c h a m a t C o m :i o f lh e retina in a IC ^yea r-
olld g ir f w ilh o u t o l h e r e v i d e n c e o f LuEierous sclerosis ! D :.
This w a s Lin in c id e r t L n l f i n d in g , a n d h e r e ye e x a m in a tio n W a s
o th e rw is e n o r m a l. N o le Ih e w h ite , f i n e l y p o ly c y s lic tu m o r
a r is i n g fro m L h e i n n e r T e lin a E layers just sU p erttjr Lo t h e lefl
m a c L.la r re g io n I I » . N o t e that m ost o f lh e r e l i n a l v e s s e l s a r e
h id d e n w ith in Eh i-в c o t t o n y tu m o r. Flu o re s c e in a n g i o g r a p h y
re v e a le d fi n c lw o ik ol retinal vessels w ilh in the L u m o r a n d
l a l e le a k a g e o f t h e d y e '.L Lin d F).
G -l: E le v a te d , v a s c u la rize d ,. parLly c a lc ifie d re tin a l m ass in
a h e a lth y 1 7 - y e a r -o ld h o y w ith n o funnily nEsrory1 o f tu b e ro u s
s c le ro tis o r re tm o h la s lo m a .
|—I : N o n p r g m e n te d , p e d u n c u la te d , v a s c u la r ize d a stro­
cytic h a m a rto m a in Lhe ju x ta p a p illa ry re g io n o f l1 4 1 -y u a r -
o id m a n w ith л 3 -w e e k h islo ry o f blurm>d v is io n in the
right e y e {J a n d K ). Th is w a s m is in te rp re te d as a m e la n o m a
b ecau se o f a n in cre a se d p h o s p h o ru s -3 2 u p ta k e test l l O O % f .
H is to p a th o lo g ic e x a m in a tio n o f the e n u c Fe a te d e ye reveaTed
il retina] a s lrtjc y lic h n m a rlo m n IL I.
11—I__I n x r i k . i r n f . i y e l .n t .-1"": I
 A careful starch should be made for the various mani­
festations |F T S C in nay patient with a white retinal tumor.
I'hese include Lhe classic triad of seizures, menial defi­
ciency., and sebaceous adenoma (fibroangiomasj as Weli
as other manifestations,- including white ash-leaf spots on
tbe skin and iris,, sofl yellow-brown cutaneous fibromas
(t'igures 13.09C and 13.10A), subungual fibromas (figure
13.i(JIJ], renal hamartomas, cardiac rhabdomyomas.. cal­
cified cerebral astrocytic hamartomas (I'igure 13.ЮС and
L>), cystic lung disease, and bony changes, including cys­
tic changes of the phalanges and cortical thickening of
tbe metatarsal and metacarpal bones.11 In 1!)У8. at the
Tuberous Sclerosis Complex Consensus Conference,
a revised set of clinical diagnostic criteria based upon
major and minor features of (he disease was firmly
established.14'
CL' and roenlgenographic techniques are useful in the
detection of intraocular tumors.I,,!' In infants and chil­
dren these tumors can appear identical to retinoblastoma
or may mimic necrotizing retinochoroiditis.10' hi older
patients they may be confused with regressed retinoblas­
toma or retinoma (Ligure S3.1K1-E), capillary hemangio­
mas of the retina, or a localized retinal scar secondary lo
previous hemorrhage or inflammation.
More recently genetic mutational analysis has uncov­
ered two distinct variants of 'LSC resulting from muta­
tions is the TS'CJ gene located on chromosome 9cj34
and the 1ЪС,2 gene on chromosome 16pl3.N '' '' 'I'hese
genes encode for ha mart in and tuberin respectively, both
of which are involved in regulation of the cellular growth
cycle. JSC УИС2 mutations are more frequent than iSC J
muLalions in palients with atsrocylic hamartoma or retinal
achromic patches.1 1
! 3. i 2 Lesions о f uncerlain e iio logy sinuilating retinal
aslrocylic hamartomas,
Л —^( . : In d o p h y t ic retina! tu m o r in л З В -y e a r-o ld w o m a n w ill:
a 3 -m o n th h is to ry o f b lu rre d v is io n in h e r left e y e ( A h H e r
p a 5C h is to ry re v e a le d c o n v u ls io n s u n a s s o c ia le d w it h le v e r at
I y e a r o f age. 11 w as d lh w w js e u n r e m a r k a b le . rhe-re w e re
iл а п у d ila te d b lo o d vessels pnesenl w ilh in Ihe tu m o r, w h ic h
was Io c n le d in lh e retina inferior lo lh e led I m a t uEa (A ).
A n g io g ra p h y tfe m o n s lra te d a n e j$ fe rt|u e va s c u la r n d w o i k
w ith in lh e tu m o r a n d late le a k a g e o f d y e fB a n d C j. M e d ic a l
e v a lu a lio n fa ile d lo neveaF o th e r e v id e n c e o f tu b e ro u s s c le ro ­
sis. The pa Lient w a s re -e x a m in e d 10 m o n lh s Liter, a n fl lh e re
was- n o c h a n g e in Lhe a p p e a ra n c e o f lh e lesion-. E x a m in a tio n
3 years a fle r h e r in itia l visit re v e a le d lh a l lh e lesion had d is ­
a p p e a re d , le a vin g o n ly a m in o r d is tu rb a n c e iin the relina in
lh e a ie a o f lh e tu m o r. B e c a u s e o f its s p o n la n e o u s d isap pea r-
a n c e r Jt is d o o b lfu l that il w as a n a s lro c y lic h a m a rto m a .
D - F : Sessile p re s u m e d a s tro c ytic h a m a rto m a in a h e a llh y
4 2 -y e a r-o ld m a n w ith re c e n l h isto ry o f b lu rre d v is io n in
the left e y e . H e h a d a sm all a n g io m a a n d a p ig m e n le d n e v u s
ot Ihe c o n ju n c tiv a ;n lh e sam e e y e . H is v is u a l a c u ity w a s
2 0 / 2 5 r lefl e y e r a n d 20 /20 , rig h t e y e . N o te Lhe ill-d e fin e d
g ra y -w h ite n in g o f lh e refiita in the in feron a sa l m a c u la r area
(a rro w h e a d s , IJ'i a n d the c y s to id m a c u la r e d e m a (a rro w ;
D ^ . A n g io g r a p h y re v e a le d e v id e n c e o f a ca p ilEa ry n e tw o rk
w ilh in lh e lesson a n d e v id e n c e o f in Irarel in a I e d e m a L a n d
F>. T w o m o n th s fo llo w in g laser p h o to c o a g u la tio n Ih e v is io n
ha tl im p r o v e d Id 2 0 / 2 0 . H e h a d n o o th e r fin d in g s o f Lu h erou s
sclerosis.
G —I: Th is 2 S -y e a r-o ld w o m a n c o m p la in e d o f b lu rre d v is io n
in Ihe left e y e . lixa m in a Lio n o f lh e ri^h-L e y e w as n o rm a l. In
lh e left e y e sh e h a d а gray, slig h lly e le v a te d relin a l tu m o r
lh al s tra d d le d Lhr? m a jo r relinal v a s c u la r arca des in Ih e s u p e ­
rior m a c u la r area 1C/. A n g io g r a p h y s h o w e d e v id e n c e o f the
va s c u la r na ture o f I his lesion ( H a n d lj. T h e re w e re n o o th e r
slig m a ta o f tuEierous sclerosis. S evera l m o n lf u later she h a d
d e v e lo fie d e x te n s iv e L a u d a tiv e m ^ c u lo p a lh y . She w a s I d s ! lo
folliK W -up .
I—I : A n e le v a te d , v a s c u la r ize d , a n d p a rtly c a lc ifie d tu m o r
d e v e lo p e d in I his E 7 -v e a r -o ld Екуу w h o w h e n h e w a s fiisl
e x a m in e d al l i t years o f ago h a d lh e ty p ic a l find ing s ot b ila t­
eral pars p la n ilis a n d n o e v id e n c e o f a n in tra o c u la r m ass.
S tereo a n g io g ra m s ( H a n d 1^ re v e a le d the h ig h ly va s c u la r
n a tu re o f this e x o p h y tic m a s s , w h ic h p r o b a h ly w as the result
ot a re a c live p ro life ra tio n o f lh e retinal vnsc-ulalure a n d filial
cells in re s p o n se to Ifte in tra o c u la r in fEa m in a to ry d is e a s e .
REACTIVE ASTROCYTIC
HYPERPLASIA SIMULATING AN
ASTROCYTIC HAMARTOMA
От. Gass had observed four healthy adult patients with
(осп I vascularized ret in;) I masses Lhal appeared similar
to astrocytic hamartomas. in two cases lhe IелLoris subse­
quently disappeared spontaneously (I'igure 13.12Л-С).'
In one boy With bilateral pars planitLs an exophytic vascu­
larized white retLnal mass developed during observation
(l-'lgure ]3.12) and k). IL is probable Lhal most of these
lesions and some of those reported in lhe literature as spo­
radic astrocytomas are products of reactive prolife rat Lon of
the retinal glial cells caused by focal relinitls, foral retinal
vascular leakage, chorioretinitis, vitreoretinal traction, and.,
less often, subretinal neovascularization. (See discussion
Ln chapter 10, p. SI 2 and Rgure 10.041-L..)
RETINAL VASCULAR
HAMARTOMAS____________________
ihere are two distinct retinal vascular hamartomas., both
of which may be associated wilh similar hamartomas else­
where in the body.
! 3. [ 3 Ret i nat ast rocy to m at reated wit h ph otody na mic
therapy,
Л - D : A 4 5 -y e a r -o ld C a ucasia п fe m a le svi Lh an и п т о т а гк а Ы е
pasL m e d ic a l h is lo rv w ilt re fe rre d fo r e v a k ia1 io n u f л р е в Ь а р -
iP a ry lu m o r EiSSocialed w ilh a s c o Lo m a in Ihe T i g h t u v e i A .
O n in ilia I e v a lu a tio n , v is u a l acu ities V A ) w e r e 2 D /2 0 in b o th
eye s. A n i I l-efef i netf, tra n s lu c e n t, y e llo w -w h ile ыс.|рк>rj ic.:i л I
m ass a lo n g lh e s u p e ro Le m p a ra l m a rg in o f Ihe o p lic d is c a n d
e xte n d iitg in k) Lhe relina W in o b se rve r! lE3i. Pfta ifiinent in lrin -
s it vessels as w e ll as- d ila te d collateral vessels w e re p re s e n t.
T h e m a c u la w a s flat; h o w e v e r , - :i :' (K u d a le s w e re p re s e n I
su pero nasal to the fo v e a , a n d a fe w re tin a l striae w u ie n o le d
in I lie p a p iJlo m a cu la -r a rea. Based o n m o rp h o lo g ic a l ( h a ra c-
Lerislicsr the d ia g n o s is o f relin a l a s tro c yto m a w a s m a d e w i lh
a d e c is io n Iо o b se rve tor p fu g rt'S b io u . A l a 6 -m o n L h vis-il, V A
re m a in e d 2 0 / ^ 0 ; h o w e v e r. lh e lip id e x u d a t e w e re n o te d l o
be a p p ro a c h in g lh e Eo ve o la ' C L F o u i m o п Iha a lte r K v o ses­
sions o f s fa n d a rd -flu e n c e p h o to rijrn a rm c Ih e ra p y f T A P ; I ..i -
m m spot c o v e r ini; Ihe e n lire ln n iG f u p I о lh e SLrpenolcMnpoTal
e d g e o l th e o p tic d isc), V A re m a in e d 2 t V 1 5 , Lhe lip id e x u -
daLt^s w e re d Lm irn h h e d , a n d s o m e gliosis o f lh e lu m o r c o l i Id
be a p p re c ia te d 1 1 » .
14. f 4 Retina! achromic patch of tuberous sclerosis.
Л: Fundus photograph of a relinal achromic patch.
I F H S fffl iir r ll l 1! ;il..' '/н- ill- F > - r r i i i , L i'::.n .l
(3.13
Retinal Cavernous Hemangiomas
Retinal and optic disc cavernous hemangiomas are sessile
tumors composed of clusters df thin-walled saccular aneu­
risms filltd with dark venous blood lhat give lhe appear­
ance of a сluiter of grapes projecting from the inner retina]
surface [figures i 3.1 ЗА, ti, El, G, and f, and 13. IGA). I hey
catt be dearly differentiated from at her relinal vascular
mat formations, including retinal lelangiectasisr retinal cap­
illary angioma (angiomatosis retinae), acid arteriovenous
mal form at ions. 2 Small isolated clumps of aneurysms
are often presen I around the tumor mass. Varying amounts
of a gray fibrous membrane may partly cover the ante­
rior tumor surface. PI astna-erythrocytic separation within
the aneurysms is common. ЧЪе caliber of the major reti­
nal vessels is unaffected by the lumor. Exudation is rare.
A small hemorrhage may occasionally be present on its
surface. Evidence of bleeding into the vitreous has been
reported in approximately 10% of cases but Is usually min­
imal and unassociated with significant visual loss [l-'igure
13.3&]'—I).17’ Vitreous traction on larger or gliolic aneu­
rysms is the likely mechanism for bleeding. These lesions
may be seen initially al any age, but lhe average age is 23
wars. Jhey are more common in females [female lo male
ratio of 3:2). Most patients have only a solitary lesion
affecting one eye; however, multiple lesions in ay occur in
one eye or occasionally in both eyes. The visual acuity is
usually normal unless the macula is directly involved with
Lbe malformation (Figure T3.15A and L). Visual loss asso­
ciated wilh macular pucker,1 ' macular traction,1" and
amblyopia1 1 occurs infrequently (]:igure 13.15G-J]. '['tie
tumor is associated with a relative or an absolute scotoma
that corresponds to the tumor size. E-'luorescein angiogra­
phy demonstrates thal the vascular tumor is relatively iso­
lated from the retinal circulation [I'igures S3.15C, D, h H,
i. K. and L and I3T6E3 and C). Perfusion of the hamar­
toma occurs but is delayed and appears incomplete, '['he
plasm a-erythrocytic layering wilhin the saccular aneu­
rysms is conspicuous in the Eater phases of fluorescein
angiography (E'igure 13.151 and I.]. Lxlravascular leak­
age ol" dye from the tumor vessels does not occur in most
instances.
1 3 . [ 5 R e ti naE c a v e rno us hem angio ma,
A —D : La r^ e m a c u la r c a v e rn o u s h e m a n g io m a o f the re tin a
was fir^t o b s e rv e d in this 1 7-y e a r-o Jd fe m a le w E io p re s e n te d
aL адее 5 years bpc^Llse o f lefl e s o tro p ia . Н о г vis u a l a c u ­
ity in the left e ye w a s 2 0 /3 0 . N o t e the flu id Eevel in s o m e o f
the in c o m p le te ly p e rfu s e d a n e u ry s m s in С a n d D . M in im a l
c h a n g e o c c u rre d in i1s a p p e a ra n с e d u rin g this p e rio d o f
fo llo w -u p , b u t Lhe visual a c u iLy d e c re a se d Lo c o u n tin g finders
on lv- i h e h a d n o e v id e n c e ol a n g io m a s e ls e w h e re ,
t a n d F : C a v e rn o u s h e m a n g io m a in the I d l m a c u la p f a
h e a llh v 7 -v e a r-o ld h o y (E ). N o le Lhe d e la y in d ye p e rfu s io n o f
Lhis Lumcir LF ■ F iv e vears later Lhe Lu m o r w as u n c h a n g e d .
^ - I : C a v e rn o u s h e m a n g io m a ol lh e retina in- a 3 0 -m o n th -o ld
girl w h o d e v e lo p e d fi^ h t e s o tro p ia at t* m o n th s o f a g e . H e r
g e n e ™ I b e a ilh anti pEryKical t'x a m i mil io n w e re n o rm a l e K C fp l
fur the p re s e n c e o f a fe w s p id e r a n g io m a s o n b e r h a n d s a n d
w rists. A n id e n tic a l tw in sister w a s n o rm a l e x c e p L fo r s im ila r
s p id e r a n g io m a s o n lh e h a n d s . T h e re w a s a n irreg u la rly e le ­
va te d va s c u la r m ass in lhe s u p e ro le m p o ia l q u a d m n l o f Ihe
rigjiL e ye (G > th a t w as c o m p o s e d o f d ila te d , o v a l o r ro u n d e d ,
ih in -w a lk 'd , s a c c u la r b lo o d vessels lhaL g a v e [h e a p p e a r­
a n ce oE a m ass o f grapes ly in g o n lh e in n e r relin a l su rfa ce
a n d p r o tru d in g in to Ihe v itre o u s . T h e tu m o r e x te n d e d fro m
the o ra serrata a lm o s t into the m a c u la r area o f Lbe rig h l e ye .
lu o re sce in a n g io g ra p h y s h o w e d s lo w a n d in c o m p le te :llin g
o f Ihie a n e u ry s m s m a k in g u p lb e tu m o r (H a n d I . N o L e d e la y
in v e n o u s d ra in a g e I a n o w , Fti fro m the area o f lb e Lum or.
A p p r o x im a le lv tO m in u te s after d y e in je c tio n Ihere w a s Mill
in c o m p le te p e rfu s io n o f Lhe tu m o r. K o L e IEkj level o f d ye in
Lhe la rg e lu m o r cyst (a rro w , If. T h e p a tie n t w a s ly in g o n h e r
Iclt sid(: in the o p e ra lin g ro o m d u rin g lEie a n g io g ra p h ic slu d v.
J - L : C a v e rn o u s h e m a n g io m a o f lh e o p lic n e rv e h e a d in a n
a s y m p to m a lic 5 1 -y e a r-o ld w o m a n . V isu a l a c u ilv w a s 2 0 $ 5 ..
An giug rapEny revea Led s lo w p e rfu s io n r p E a s m a -e ry tb ro c y tic
s e p a ra tio n , a n d m in im a l s ta in in g iK a n d L ) .
:< -L, iTLirn LI.lss. ' I
Retina! :гчь_ггЛ]r iinjjwrtcwws I 1 23
 Whereаз most relinal and optic nerve ca№ nous hem-
angfemas occur sporadically, there es evidence that some
p.itient-ы may have a dominantly inherited neurocutane-
ous syndrome Lhal includes cavernous hemangiomas
of" tSie optic nerves-., chiasm, optic tracts, the preralandic
area of lhe cerebral cortex, Lhe midbrain,. brainstem, and
cerebellum [E'igLLie 13.171). as well as the skin (figure
13 £7J:) 15 7 , ЬЧ1.1 1Г5-
ha mil ial cavernous hemangioma has been linked Lo
three loci on chromosomes :5q, 7p, and 7q._ Familial
cases of cerebral cavernous malformation (FCCM ) ]S' are
associated with mutations in K R I'fi (G C M l), MGC4&07
(CCM2J, and РЩ П 10 (C C M J) genes. С Ш 1 is located aL
chrojnosome locus 7qtl-q22 and was Lbe first one identi­
fied with the familial form of CC.Vls. C C M l mulaLion is
involved in 40 - 53% of familial CCJVls and nearly half
these patienls have neurological manifestations before
25 years of age. CCM_2 is located at 7p 15—13 and muta­
tions in this gene are involved in up to 25-40%. of famil­
ial CCMs. Ihe numbers of lesions increase less rapidly
with age in patients with C C M l Lh.m with O CM l disease.
CC.V13 is localized at 3q25.2-cj27 and is the least common
of mutations (Ю % ), but has near 100% penetrance and
palients are more likely lo present xvilh hemorrhage and
become symptomatic before 15 years of age."'
The angiomas of tbe brain may cause seizures or sub­
arachnoid hemorrhages. Twin relinal vessels, defined as a
pair of vessels, separated by less than one venule width,
that run a parallel course for more than 1 disc diameter.
Located al least 2 disc areas distant from the optic disc.,
have been described in carriers as well as affected members
of families with cavernous hemangiomas of the eye and
brain, as well as in EamiLy members of palients with von
1Lippel-JJndau [ V I IL.) disease.11'" Cavernous hemangio­
mas do not increase in size. Lhe amounL of fibrous tissue
on the anterior surface increases over a period of lime and
es associated with partial ob!iteration of the tumor.
HislopathologicaMy, the lumor is composed of mulliple
Lbin-1walled interconnecting aneurysms of variable size,
occupying the inner hatfof the retina and in some patienls
the optic nerve (l:igure 1S ;l? A^O) j!sfM 7- lJ£r190 The
endothelial lining of Lhe- large vascular channels ultrastruc-
turally appears normal.1"" lhe gray membrane LhaL over­
lies part of the angiomas in some cases is of glial origin.'''u
PholocoaguLation has been used to obliterate these
Lesions bul Es unnecessary as Long as the patient shows no
signs of developing vitreous hemorrhage.1 1"' In one
case of severe vitreous hemorrhage, the lumor was partly
excised during a pars plana vitrectomy.14 Some of the
cerebral cortical angiomas causing seizures or subarach­
noid hemorrhage may be resectable.'" '
E3. i Fi R e t ina! cavernous hemangioma,
A - G : C a v e rn o u s h e m a n g io m a d is c o ve re d in a 2 7 -y e a r -o ld
т ж т w h o was; iiospi Ia I i z e d b e c a u s e a f a g ^ n fc ^ Jiz e d sei­
z u r e . A n e fe c lT o e n c e p h a lo g ra m re v e a le d io w vo lLa g e in
Lne left c e re b ra l h £!m i sf l Ь гте . A skull ro e n tg e n o g ra m a n d a
ca ro tid arleriograTn w e re n o r m a l. H e r fa lh e f d ie d о 4 fJ years
o f age w iL h staLus e p ile p lic u s . A u t o p s y o f Ihe fa th e r re v e a le d
fi fo c a l c a v e rn o u s ^fefflalW fO m a in the m id b r a in , p o n s , a n d
c e re b e llu m -IFigure 1 0 .2 0 F ) . T tie w o m a n 's e y e e x a m in a tio n
was n o rm a l e s c e p l fu r Ihe p re se n ce p f a s lig h tly e le va te d ses­
sile c a v e rn o u s h e m a n g io m a in v o lv in g lh e in fe ro n a s a i q u a d ­
rant o f the rigtjt e y e ( A I. A sm all suLjieLinal a n d d e e p relinal
h e m o rrh a g e w as p re s e n t fa rr o w , A . A n g io g r a p h y re v e a le d
d e la ye d a n d in c o m p le te p e rfu s io n o f lh e c a v e rn o u s h e m a n ­
g io m a (B a n d C h N o t e e v id e n c e o f p la s m a Layering (arrow s^
a n d m in im a l e v id e n c e Ы e xtra v a s c u la r escap e o f d y e . A g e n ­
eral p h ys ic a l e x a m in a tio n re v e a le d a s lei late a n g io m a Lous
h a m a r lo m a ot lh e right c h in a n d several ch e rry a n g io m a s o f
lh e th ig h .
D and F: T h is 45-y e a r-old o th e rw is e h e a lth y m a le s u ffe re d
c o n s la n l s evere h e a d a c h e for 5 m o n Lh s associated w i lh
o c c a s io n a l d rzzin e s s a n d n a u s e a . H e h a d n o visuaE c o m ­
p l a i n t . M a g n e tic re s o n a n c e im a g in g o f fils h e a d to e v a lu a te
h e a d a c h e re v e a le d m o r e th a n 5 0 s m a ll v a s c u la r m a lfo rm a ­
tions in va rio u s parLs o f his bra!ri ■L i_ There w as a fa m ily h is ­
to ry a f s p in e a n d n e c k lesions in his sister, a c o u s in w i lh
b ra in a n d a b d o m in a l tum ors., an u n c le w ilEi a Etrain le s io n ,
a n d a so n w it h e p ile p s y . H is v is io n w a s 2 ( Y 2 0 tn e a c h -eye.
H e h a d .J - 4 a n e u ry s m a l d ila tio n s in the far te m p o ra l peri p h -
ery erf his le ^ fu n d u s ( D ) . T h e right e y e w as n o r m a l. B o lh he
a n d his sister w h o w a s e v a lu a te d at Ih e M a y o C lin i c , w e re
p o s itive for C C M ! ge n e at lh e 7q locus Lhat c o d e s for K R 1T 1
p ro te in . H e tested n e g a liv e for the VI IL g e n e .
F - K : Th is 1 З -у е а г-o ld girl p re s e n te d w ith floaters s e c o n d a ry
Lo s p o n ta n e o u s v jlre o u s h e m o rrh a g e fro m th in -w a lJe d s a c c u ­
la r m a lfo rm a lio n s in h e r lefl e y e (F, H , J, a n d К . T h e lesions
w e re e x te n s iv e , in v o lv in g the s u p e r io r h a lf oE the fu n d u s .
Several o f Lhe a n e u fy s m a l w a lls w e re m a d e u p o f glial Tis­
sue a lo n e ; Lhese d id noL lil! W ith flu o re s c e in la ir o w s , F a n d
C . . T y p ic a l se pa ra tion o f b lo o d cells a n d p la s m a w a s seen
in s o m e o f ih e m in Lhe late a n g io g ra m s it). O f s ig n ific a n c e
is the in v o lv e m e n t o f Lhe largtir v e in w a lls w iLh Lhe m a lfo r­
m a tio n 'iarrnjw h e a d s , F a n d C l , w h ic h is u n u s u a l since Lhese
a n e u rys m s are b e lie v e d to o c c u r al lh e c a m fla ry le v e l isee
Fig u xe 1.3 .1 (>L . ih e w a s kep i u n d e r o E jtc rv a tio n a n il the v il-
ruous h e m o rrh n g e cleartsd o v e r 5 m o n th s w iLh o u l Erealm enl
iK j. S h e hacf a n ipsi lateral c a ve rn o u s т а Ilorm a Li o n o f Ihe
c o rp u s ca I Lo s u m . d e n e Lesting is u n d e rw a y .
i'11jn1 ifisctfiif? Hnjjttfriiwwj* I 125
 In the past, retinal cavernous ftemartgJcma was not
recognized a i a distinct retinal vascular hamartoma. r['he
more sessile and smaller lesions (l-'igure 13.1 ^A} were
often misdiagnosed as congenita] retinal telangiectasis.''■1‘
l:Egure 13.1615 diagram malic,illy indicates the basic struc­
tural difference between retinal lelangieeLasisr which is a
congenital anomaly affecting the structure and integrity
of the intrinsic retinal vasculature, and a retinal cavernous
hemangioma, which li a localised vascular tumefaction
composed of cavernous vascular channels that are partly
isolated from normal relinal circulation. Some of the
more globular retinal cavernous hemangiomas have been
reported in the older literature as angiomatosis retinae.167
It is uncertain whether the retinal vascular lesion
reported in one patient with CNS symptoms and the der-
matologic disorder angioma serpiglnosum is relaLed Lo
retinal cavernous hemangioma.l! 1 A lesion that angjo-
graphically was similar to a retinal cavernous hemangioma
was observed in an infant with blue rubber bleb nevus
syndrome.1" 'I'he fact that the lesion spontaneously dis­
appeared over a 4-month period suggests that it may not
have been a cavernous hem an git) ma.
!3.E m Continued
L : D ia g ra m s h o w in g strifeiLHraJ cliffenencet u f: ■l.i n o rm a l rc?Li-
n a l vessels; (21 d fflu s e a n d focal V a a c u lif d ila tio n a n d per­
m e a b ility a lte ra tio n in retinal te la n g ie c ta s is : ^ n d .J) lo c a lis e d
vascu Jar m a lt o m i.n io n ih a ftia ita m a ) arisin g fro m I h o c a p il­
la ry b e d in ra V En V a LIS h e m a n g io m a .
IA j n d Li. fre jn ; С л и ' l o l i t Ll^ v' U r. M ip h u i J K n n .-
13.1, Re ti nat cave rno us hema ngso ma.
Л a n d 0 : H is to p a L h o k jg ic c o n d itio n o f q^yenfltpus h e m a n ­
g io m a o f Hit? rutina in a 2 -y e a r-o ld girl w h o s e e y e enu-
C leaLed w iLh lh e m istaken d ia g n o s is o f re tin o b la s to m a . The?
sessile reLLnal Lu m o r w a s c o m p o s e d o f m u ltip le , th ir-w a lle d ^
d ila te d b lo o d vessuls that тepla c od I h r in n e r h a lf o f Lhe reL-
tna (A f. T h e a rro w in d ic a te s p ig jT te n l-la d e n m a c ro p h a g e s
in Lhe subTelinal s p a c e . Г ho relin a l d c la c h m e n t w a s а И i fa c­
titio u s . A h ijjh -p o w e r v ie w o f Lhe lesron re p e a le d d rla lc d .
e n d o lh e I i u rn -lin e d aneiJfy$ № S in te rc o n n e c te d l>y n a rro w
channels. (a n tjW s , И ) . rheso r e la tiv ity isola tod v a s c u la r sac­
cules a c c o u n t fo r th e slugg ish c irc u la tio n a n d p la s m a -e r y lh -
ro c v lic s e p a ra tio n d e m o n s tra te d a n g if^g ra p h lq a ll^ in Lhese
le sio n s.
f . : hljsL(>1o jjiс c o n d itio n o f c a v e rn o u s h e m a n g io m a o f the
o p tic п е т ™ a n d a d ja c e n l ru lin a .
D ; H is to p a lh o lo u ic c o n d itio n of a retrobulEiar ca ve rn o u s h e m -
a n g jo m a o f Ih o oplic n erve iHiad. lh is w a s a n in cid e n ta l fin d ­
in g in lh e o p tk n erve o f a 3 - m o n th -o ld w h ile g id w h o w a s
b o rn p re m a tu re ly w ilh a biTth w e ig h t o f 2 lb 1 4 q 2 ( l j kg),
i : A s lig h lly m ised c u ta n e o u s c a v e rn o u s h e m a n g io m a o n I ho
a m i o f a pa tienL w ith a retinal c a v e rn o u s h e m a n g io m a . This
paLienL h a d tje n e ra iize d s e izu re s . O n e s o n , w h o h a d m u ltip le
c u ta n e o u s a n g io m a s o n Lhe fa c e , lr?g, a n d lo o l, d ie d s o o n
afler surgical e x c is io n o f a c a v e rn o u s h e m a n g io m a o f the
b ra in .
f : C a v e rn o u s h e m a n g io m a o f the m id b ra m in lh e faLher o f
Ihe paLient illuslTaled in Fig u re 1 3 .1 6 A - C .
IА ; Ггоп> H a ^ i r t .li i H Zlrnfjrtunn j n 1 ft. Гru m G n u 1 ' rn iu i D n l e i urtd
11'iuiTiiи i 1 ' Ц Ir o in S p e n L i h ' ^ ; 1, '- U L irlL iiy h jI'U r . L . L . C ..i :к iгih; ]-. fnnrn
(i.Lsa.^7!
Retinal Capillary Hemangioma
'■lhe terms "retinal and oplic disc capiE]ar\ hianAngtoraa®*
Angiomatosis retinae/' and "топ ftippel's d i s e a s e " a r e
used ^ n jM m o u sly to refer to congenital hereditary cap­
illary angJomatoM hamartomas of the retina and oplic
nerve head,1™ 3316 When associated wilh C'KS and other
organ involvement the condition is referred to as von
i Jippel-l.indau disease VHE..JUIJ': ' VI IL disease is a domi­
nantly inherited system!# ha mania thal includes not only
capillary angiomas of lhe retina, cerebellum, brainstem,
and spinal cord, but also angiomas, adenomas, and cysts
affecting the kidney, liver, pancreas, epididymis, and meso­
salpinx.■v ' The diagnosis of VH L is justified when either
a relinal angioma or a t!NS angioma occurs together
wilh one or more visceral cysts or tumors in one patient
or when a single lesion of the VHL complex is found in
a relative al risk. Ocular manifestations of VHL are oflen
Lhe first Lo appear. Retinal angiomas acid CN:S angioma
both eventually occur in approximately 50% of palients
with V H L Pheochromocylomas occur in approximately
10% of patients wilh V H L.301203'206 Approximately 23%
of patients wilh V IIL develop clear cell renal carcinomas,
typically during the late slages of the disease.1
Polycythemia occurs in approximately 1.5% of patients.
JVvin retinal vessels, a retinal sign of dominantly inherited
retinal cavernous hemangioma (see previous discussion of
retinal cavernous hemangioma], occur in approximately
70% of patients with familial VHL disease and En 5tl%
of at-risk family members without ocular angEomas.221
Since most patients who present wilh a solitary retinal
angioma and a negative family history suggesting VI-EL
fail Lo show other evidence of the disease, the medEcal
evaluation of these patients wilh sporadic tumors prob­
ably does not need lo be as comprehensive as in patients
wilh multiple ocular tumors or other evidence of familial
involvement Identification of the VHL gene on chromo­
some Зр25-26 has now made it possible for suspected
individuals to undergo genetic testing wilh a high degree
of accuracy.J J --JJ1
Capillary hemangiomas are typically red or pink tumors
thal may arise from the superficial retina or oplic nerve
head and protrude inward (endophytic angiomas) (figures
13.18A-1. A l l , K, 13.191:1, and 13.2DO-1). When located
peripheral, lo the optic disc, these endophytic tumors are
usually associated wilh arteriovenous shunting between a
dilated tortuous feeding artery and a draining vein (E'igure
13. and I ] . Capillary hemangiomas may also arise from
the outer retina! Layers (exophytic Capillary hemangiomas)
[Figures 13.1 SB. 13.t9A, A-EEE, A-IV, I3.20A. К and G, and
13.21 A and D-Г). These lumons are usually not associ­
ated wilh evidence of arteriovenous shunting, and there
is л predilection for them lo develop in the juxlapapillary
13*1# Retinal capillary hemangiomas
A ' D iagM in showing Sites-of diafcin o f feLEnal c a p illa n Angi­
omas. I, EndophytEc angioma of Lhe optic nerve brad. II.
Endophytic peripheral retinal angioma. Ill, Exophytic juxla­
papillary angioma. IV, Exophvl k' peripheral relinal angioma.
V, In I raneura I angiom.i.
B - D : Th is 3 6 -y e a r-o ld w o m a n n o te d b lu rre d v is io n in th e [eft
e y e c a u s e d b y a ju x ta p a p Eila ry c a p illa ry h e m a n g io m a (a rro w ,
A ) . S h e h a d n o o th e r stigm ata o l v o n H E p p e l- L i n d a u d isease.
S te re o s c o p ic a n g io i’ M plTy re v e a le d Ih e seshile c a p illa fy a n g i­
o m a to u s na ture o f Lbe lesion --CI a n d D l .
t - J : Ju x M ip a p illa iy (E) a n d p e rip h e ra l C a p illa ry h e n u n ^ io m a
ij- in я Щ -у к а г -o Ed girl wilili n o e v id e n c e o f ex.1 ra o c u la r
in v o k e m e n l w ilh angioTrm losjjs. A n g io g r a p h v fo v e a led lh e
cj-iapillniy n a tu re o f lb e Lu m on i ft! a n d H i. s h u n tin g o f b lo o d
fro m lb e fiiterinl Iо lh e venous- side o f the crrcu lal io n 5л th e
reg ion o f the |ie rip h e n ]l lu m o r : I—I!, a n d ta le staining ! iin d Jj.
A , Iю т G a t i.'
area. When they arise in this area they are frequently ses­
sile and may be misdiagnosed as papilledema or fiitta-
papillary choroidal neovascularization because of Lheir
predilection for causing juxlapapillaiy serous delachmenl
of lhe ret Ena and ci rein ale exudation extending into Lhe
macular region [figures 13.I8B. J3.20A. h and G r and
13.21A and K).1''' : Loss of cenLral vision may occur sec­
ondary to the accumulatEon of yellow, lipid-rich exudate
in the macula derived from peripheral relinal angiomas.
The mechanism for this accumulation is similar Lo Lhal in
palients wilh peripheral retinal telangiectasia (see Chapter
6). I.oss of vision may also be caused by an epEretJn^J mem­
brane distorting the macula remote from lhe site of Lhe
angioma (figure 13.19A-C). There is a striking predilec­
tion for these e pi retinal membranes to peel spontaneously
and for vision to return to near normal after ireaLmeLit of
the peripheral angioma (E'igure 13.19A-F)bl57,35fl,J25-22? ten
this reason, vitrectomy for excision of Lhe epirelinal mem­
brane should be considered only after a 4-Cvmonlh period
of observation following treatment. Heaters and visual loss
may also be caused by development of a retinal Lear adja­
cent lo an angioma and subsequent rhegmatogenous relE-
nal delachmenl ■Jl' Vitreous traction developing al lhe
anterior surface of the relinal angioma and adjacent relina
is responsible for lhe retinal tear. Vitreous traction may
also be a factor in the development on Lhe lumor surface of
proliferative retinopathy, vilrecus hemorrhage either spon­
taneously or following treatment of the tumor, and trac-
lional relinal detachment. A retrobulbar capillary angioma
(Rgure 13.]&A-EiJ should be considered in patEenls wElh
angiomatosis and unexplained visual loss.
 pffereostaple fluorescein ingtogrdphy is invaluable in
detecting exop hylic sessile juxtapapillary capillary hem­
angiomas (Figures 13. lfiR and 13.20).[^ Because these
Lumors prolrude into the subnelinal space adjacent to the
optic disc and because they frequently лrise in the papillo-
macular bundle area in symptomatic patients, ihey are dif­
ficult to treat with photocoagulation (Jlgure 13.2ffi\-F and
G-L). Muorescein angiography in peripheral endophytic
Eesions shows evidence of arteriovenous shunting (figures
13.IS] and 13.191). Angiography usually shows no evi­
dence of fluorescein lin in g in the macular region in
those patients with lipid-rich accumulations secondary to
peripheral angiomas. Angiography is particularly useful in
the detection of very small lesions lhal may be barely visi­
ble biomicroscopically [Figure 13.19В and fc).156-215-^-233
I.ight and electron microscopy reveals lhal these tumors
are composed of a mass of retinal capillaries, many of
which have a normal endothelium, basement membrane.,
and pericytes (Hgure i&.lfz)^00-23*-233
13. 1Я Ret in at capi Clary he mangiom as.
A —F : P e rip h e ra l re lin k I c a p illa ry a n g io m a s IA a n d B : a n d
m a c u l a r p u r s e r :C'i i гь а 2 .1 -y e a r-o ld w o m a n c o m p la in in g o f
rece nt 1оън o f ce n tra l v ini a n in t h e rig h t e y e 1. H u t pasl m e d i ­
cal history a n d fa m iEy h is to ry w e re u n re m a rk a b le . V isu a l
E if u i iy in 1h e ri^hl e v e w a n 2 0 / 7 0 a n d in Ih e le f t еуч? w a s
2 С У Э 5 . In a d d itio n 1o I I » s o lila ry a n g io m a in Ihe s u p e ru te m -
p o ta l fu n d u s I.A i_. th e re was; а sm all a n g io m a л а га Ik' Harrow,
E ) . Flu o re s c e in a n g io g ra p h y d e m o n s Lra le d b a th Lesions ( D
a n d t : . T h e Г(?г1т1-а3 lu m o rs w e re trea led w ith с гу о р с л у a n d
p h o lo c o a g u la tio n . S*>on a fte rw a rd i h e p re fe tin a l m e m b r a n e
5p u n r a n e u u 5.lv d r ta c h e d fro m Ihe in n e r s u r f a c e o f [he m a c u la
a n d re m a in e d a tta c h e d Co t h e o p tic n e rve h e a d (a rro w , F>.
H e * v is u a l f r u i t y i m p i i № ^ l In 20/215 - 3 .
G —K : La u d a tiv e m a c u lo p a th y ( G J c a u s e d by a n e n d o ­
p h y tic a n g io m a nasal to Ih e right o p lic d is c { H a n d h In this
2 3 -y e a r-o ld w o m a n w h o p re s e n te d w rilh a 2-m oroLh h is to ry o f
bffarred v is io n In Jb e rig h t e v e . H e r fa m ily h is to iy a n d p;jsl
m e d iita l IniutoTy w e re r e g a liv e . C q fiip u le a Lom o f^a plTV scaji
or the b ra in was n e g a tiv e . Visuial a i'u ity w as 2 0 / 7 0 , rit’ hl eye,
a n d 2 0 /2 0 r left e;ye. La s e r p h o to L o a g u la tio n o f the feed er
artery a n d lu m o r Tesulled ir> a v ilie o u s h e m o rrh a g e ijj. i i x
years 3ater h e r v is u a l acuiLy w as 20/-4Q. Is'ole 1he v ilre o re lin a l
tra c tio n , nasal d is p la c e m e n t o1 the o p lic di^c a n d fo v e a l c e n -
ler la iro w , K .1, a n d resol и I io n Dl" th e m a c u la r o x u d a lio n .
i'11jf 11 'i ifisctfiif? Hnjjttfriiwwj* 1131
 In some cases., capillaries making up these tumors may
show abnormal fenestrations.' ' ' J' i6 Stromal cells, which
some have attributed to astrocytes, separate the vascular
channels and frequently contain large l i p i d -filled vacu­
oles. Jt is doW believed that Lhe true neoplastic component
(i.e.. the cells with atlelic deletion al the VH L gene locus)
are the foamy stromal cells."1'' 'ihe VJ El. protein (pVHE.)
Largets hypoxia-inducible factors f o r degradation. In the
absence o f pVl IE. there es excessive p r o d u c t i o n of vascular
endotheli;il growth factor. ' N e w vessels may develop on
the anterior surface ol" these tumors and extend into the
vitreous (E'igure 13.1215). Eixophylic tumors may have vas­
cular communication with the choroid in some cases.
Because of their capillary nature and predilection for
Lhe development of arteriovenous fistulas and exuda-
Lionr these tumors are capable o f reaclive proliferation
and continued growth even into adulthood. Progressive
intraretinal and suhretinal exudation and detachment
are part of the natural course of the disease. Spontaneous
fibrolEC involution o f angiomas, however, occasionally
occurs/1 IdeEtlLfication of capillary angiomas oph-
thalmoscopically and by fluorescein angiography during
the earlv stages is important because treatment with pho-
tocoagu lation] W '230*242-144 or o y tr th ^ p y 1
at this stage of the disease is easier. Treatment o f retinal
capillary hemangioma is based upon lum or size, loca­
tio n presence o f subretinal fluid or relinal tractionr and
visual acuity."'1:4 lhe sessile exophytic juxlapapilLuy hem­
angiomas associated with loss o f macular vision are diffi­
cult to treat because of the frequency wiLb which they are
Located in the papillotnacular bundle and because laser
treatment is ineffective in stoppitig the exudation derived
from the outer portion o f the tumor that protrudes into
I 3.2H Relinal capillary hemangioma,
A —E : Sessile ju x L a p a p illa ry re tin a l a n g io m a (A ) m is tfia y n o s e d
as p a p i 11 u d e m n in a j! 1 -y e a r-o ld w o m a n w ilh a 5 -m o n lh
h is lo ry o f inlorn-iallenl h e a d a c h e s . She Иле I necenlly b e e n
h o s p ita lis e d fo r a th o r o u g h n e U rp lc ftfG e v a lu a L io n , w l i k h
was гм?цдLive. H e r vis u a l a c u ity in E » L h e ye s w a s 20 /20 .
A n g io g ra p h y re v e a le d a c a p illa ry a n g io m a , la rg e ly c o n fin e d
Lo Ihe.1- o u le r '.w o -l b if ds o f I lie rtJl i гтл iE3 a n d C J , 5 b e d e v e lo p e d
c h ro n ic serous rieLachm tiTil o f Ihe m a e u la , a n d h e r vis u a l
a c u ity d e c re a se d Lo 2 0 /5 0 in Г he e y e . i h e h a d Lw o
courses o f a rg o n iaser f^rid p a tle rn lnea lm ent ■I.?I Lo lh e tu m o r
lhaL resulted in re s o lu tio n o f Lhe in tra re tin a l a n d SLfbrm inal
e r u d a le ; t l . A L lh e tim e riF h e r last p h o to g ra p h , m arie 9 years
afLet her iriilial Ire a Lm e n t, her vis u a l a c u ity w a s 20 /3 0 .
F - L T h в 1 9 -y e a r-o ld м т л п b a d а h isto ry ot b lu rre d vis io n
anti o p l it d i-sc lesions firsL n o lo d aL age la years. S h e w a s
a .^ y m p to m a lu in the righl e y e . V is u a l a c u ilv w as 2 0 /3 0 , righl
eye^ aTid 20/40(5, left e y e . T h e m w as e x u d a L iv e m a c u lo p a th y
associated w ilh a ju x la p a p illa ry c a p illa ry a n g io m a b ila te ra lly
(a rro w s , F a n d ( J l. The a n g io m a in lh e left e y e w a S Inna Led
w iLb a r^ o n jjruen laser - H i anri w a s reLreaLed 4 m o n lh s later.
A l that tim e Lhe a c u ity in th e right e ye h a d d e c re a se d lo
2 0 /5 0 a n d Ih e a n g io m a ■:I w as LreaLed w ith laser. C in e m o n lh
Iа к т lh e a n g io m a i гг the fi^ h t e y e <JC] w a s net Tea. Led. F o r ty -L w o
m onLh s laLer her visual a c u ity in the rij^hl e ye w a s 20v'40 nind
Lhe left e ye w a s 2 (V b O . There w a s iTnp rm iem ent in lh e e x u d a ­
tion in b o lh eyes :l a n d L:-. A I th e lim e ot h e r ifiilial e x a m fn a -
Lion m a g n e tic re s o n a n c e im a g in g o f the brain re ve a le d a left
ce re b e lla r h e m a n g io b la s to m a th a t w a s s u c c e s sfu lly re m o v e d .
There w a s n o fa m ily liis io ry o f a n g jo m a lo s is .
the subretinal space. Ihe use o f photocoagulation to create
a barrier between fuxtapapillary angiomas and Lhe center
of the macula before Lhey cause macular detachment and
exudation may prove Lo be o f value (I'igure 13.1515-1).
JJfИ iinwfirtcwws I I 33
 Treatment of the peripheral angiomas with pholo-
coagulalion or cryotherapy or both Ls. generally effective
[ ij lesions whose diameter dots exceed ] disc J i лmeter
Ггеа^тпехЙ of larger Lesions is complicated by excessive
sub retinal exudation and a predilection for the devel­
opment of ret ini its proliferans on lhe surface of these
tumors, lechniques for treating large retiп,зL angiomas
Include repealid applications of laser to the feeding artery
to reduce the tumor perfusion before treating ihe tumor
directly, use of transsderal penelraling diathermy. and pars
plana vitrectomy and direct diathermy to ihe tumor21'■
lhe use of л transvitreal arterial clip together with dia­
thermy л nd removal ol' the posterior vitreous may prove
Lo be useful in the treatment of large angiomas.' ' Surgical
excision of Lhese Lesions has been reported/' "
l>holodynamic Lherapy has been tried M lb moder­
ate results to induce the occlusion of boLh iuxtapapillary
and peripheral retinal capillary hemangiomas [Figure
13.2.^.352-255
13*21 Natural course of retinal capillary
hemangiomas.
Л —F : E x o p h y tic c a p illa ry a n g io m a in а 1 7 - ye a r-o ld E>oy
p la ih ln g O f Eilurred Ы о п in Ihe raft e ye farr®Ws, A a n d В ). Л1
lhal tim t Iliors? y v e ft n o o th e r lesidfis ;n rbi Iher e y e . .M o d i f л I
eva I ил I i o n fo r e x tm o c u la r e v id e n c e o f a h g i i x T u ^ s w a s n e ^ -
л1 ivt?. O r e l I lie s u b s e q u e n t 1 0 yJSirs h e k .id g ra d u a l a rg u ­
m en t o f the a n g io m a to u s m ass LhaL g re w th ro u g h lh e center
o f his m a c u la d e s p ite laser p h o L u c o a g u la tio n . D u r in g Lhis
И т п h e d e v e lo p e d а sm all a n g io m a in Ibu in II1л о г tundus- ol
Iho Siimt1 eye jwid л small atigiafflS on the ngbl a'pfljfc clist
(arrow, O . This remained unchanged from 1979 until 1Э92,
when ho relumed bccause he bad noticed a paracentral r c o -
Loma in the right eye (L3.I. Meanwhile be bad developed total
re1in.il delacbrn-un! ,uid had no lij^hl perception in ihe left
eye. La*er treatment -a]c.vnthe temporal margin df 1hnj tLimor
was advised iind was rerusi'd. hie returned in 1495 com­
plaining of difficulty reading. His acuity was 20/15 hut ho
had a large cecoci'nlral scotoma associ-ated with exudative
retinal detachment and further enlargerrtenI of the angioma
II . tn a n ol'forl I о isolate (h o tu m o r fr o m the c e n te r o f Lhe
m a c u la a ro w oi la y p to n rc^J laser bilrtis w a s p la c e d n e a r lh e
te m p o ra l m a rg in o f lb e tu m o r I'arnow, Fjt N i n e m o n th s later
lh e OK -jd a le W as g o n e a n d h e w a s a s y m p to m a lic .
G —i : G r a d u a l e n la rg e m e n t ol je x la p a p ilL iT y a n g io m a
o c c u rre d in this pa LienL. C , M a rc h 1 9 Э З . H . M a r c h 19-S5 . I.
S e p te m b e r 1 9 9 o . Several years later th e p a tie n t had se vere
lo s t ol central v is io n E K v a u s e o f e x u d a tiv e retinal d e la c h -
m e n t. U s e o f a b a rrie r-ty p e laser tre a tm e n t a n d d irect treat­
m e n t o f Ih e a n g io m a e a rly it! a n d H m a y h a v e p re v e n te d or
d e la y e d Lhe los-s o f ce n tra l v is io n .
J-L: A jus(1apapillar> a n g io m a '.a rro w s, K< d e v e lo p e d 5
years later at Lhe site o l a c h o r o id a l ru p tu re I a m o w , Jl in this
1 9 -y e a r -o ld w o m a n w it h 5 targardt's d isease. H e r sister b a d
SlargHirctlt^s d ise a se , tnil h e r fatrrily his Io n w as n e g a tive o th e r­
w is e . This tu m o r m a y b e a s e c o n d a ry a n g io m a resulling fro m
re a c tive gfral v a s c u la r p ro life ra tio n at th e site o f c h o rio re tin a l
scarrin g .
|C j I, c i H j r l L - ' . y c l [ J r . A r n o l d t 'j l j c l- L .. Гг< лп R d t i t e ( 4 I .14 '■
©
 Most recently, systemic and btfravltKat administration
of inhibitors of vascular endothelial growth factor have
demonstrated miAcd treatment outcomes, suggesting (hat
the general eflicacy of anti angiogenic agents in VHL Lb
uncertain.156'^ 6
The differentia] diagnosis for juxtapapillary capillary
angiomas- includes- juxtapapillary choroidal neovascu­
larization, hypopigmented combined retinal and RPE
hamartoma, papilledem a/^71'" juKlapjpillary choroida!
hemangiomas and osteomas, and reactive retinaE glial
and vascu.Ear proliferaticm (sec discuss ion in the nest sec­
tion) Stereoscopic fluorescein angiography is the most
important study in the differential diagnosis. Ih e diag­
nosis of peripheral capillar)7 hemangiomas is not diffi­
cult in the presence of a dilated, tortuous retinal artery
and w in extending from the op Lie disc to the tumor.
Vaioproliferative tumor can be mistaken for a peripheral
retinal angioma.
I 3-.12 Hi stopa th ology al ret iпа I cap iIla ry
hemangioma.
A - D : H is to p a th o lo g ic c o n d itio n o f p r e -e x u d a tiv e ph ase o f
relinal a n g io m a in а -i3 -y e a r-o Id ш й п w h o c o m p la in e d o f
parjpbthesjas Ы Ih e arm s a n d logs. IHis m o th e r h a d d ie d o f a
Lira in iLlmoHf at 4 0 yeare o f £ g e . H is ПеигтиЬоГс e x a m in a tio n
was- n o r m a l. H is c e re b ro s p in a l flu id p ro te in w a s .10 0 m g .'d |
A m y e lo g ra m re v e a le d a b lo c k л! the firs I c e rv ic a l v e rte b ra ,
a n d a rig h t b ra c h ia l a rte rio g ra m re vea led a large va s c u la r
tu m o r a I Lhe level o f the b ra in s te m . A c e re b e lla r Ere m a n a lq -
b la s lo m a w a s fo u n d aL lh e l:m e o f < ra n io lo m v . i he parienl
d ie d s o o n a lle rw a rd . A n a u lo p s v re v e a le d m u ltip le cysts o f
the ri цЬ| k id n e y а пт;' p a n c re a s . C ro s s e xa m in a li-n n o f lb e righl
e ye Revealed I w o n o d u la r re lina l a n g io m a s . The larger o n e
(arrtjw . A ) m e a s u re d 1 .5 m m . The relina l vessels le a d in g lo
b o lh angjtem as w e re d ila te d . H is to p a th o lo g ic e x a m in a tio n
re v e a le d d ila te d fe e d e r vessels (a rro w , E?1 s u p p ly in g Lbe c a p ­
illa ry lu m o r, w h ic h re p la c e d the n o rm a l retinal a r c h ilectu re
a n d p n o lru d e d in to the vilruoj.is c a v ily . A h ig h -p o w e r v ie w o f
Lhe tu m o r s h o w e d Iha L it w a s c o m p o s e d o f c a p illa ry -s ize d
b lo o d vessels lin e d b y fla tte re d endcriheJial ceils (C ). SLrands
o f fib ro g lia l tfS-sLie a n d c a p illa rie s w e re p re se n l o n the su rfa ce
o f lb e Lu m o r a n d e x te n d e d anlo th e vrtra ous la iro w , D ) .
E a n d F : С.! I ini с о р а Ih o lo g ic c o rre la lio n o f a n e x o p h y tic c a p il­
lary a ngp om a o f the o p lic n e rv e h e a d a n d p e r ip a p illa r y relina
s im u la tin g c h ro n ic p a p ille d e m a in a 2 9 -y e a r -o ld rn-an w h o
firH! n o te d b lu rre d v is io n in his right e v e in 1^ )5 9 . 3-1 e h a d
slm rtar s w e llin g o f b o th o p tic discs associated w ith e x u d a tiv e
d e la c h m e n l o f the s u rro u n d in g retina -it j. CJuGf Ih e subse-
q u e n l i years h e had p ro g re ss ive Joss o f v is io n in b o lh eyes^
a n d b e c a u s e o f Lhe u n c e rta in ty o f Ih e d ia g n o s is :h e lefl e ye
was e rn jt Ic a to d . H is fa m ih ' h islo rv w a s p o s itiv e fo r an a n g io -
b la slic m e n in g io m a in hi к m o lh e r, a p h c o c h r o m o c y L o m a in a
n ie c e a n d a n e p h e w , a n d b ila le ra l o p lic n e rve lesion s s im ila r
Lo lh o s e in Ihe p a lie n L in a n e p h e w . H is to p a th o lo g ic e x a m i-
n a lio n re v e a le d a n eKoph/yli.C capiillaiy h e m a n g io m a in v o lv ­
in g the ju x ta p a p illa ry retina a n d o p tic n e rv e h e a d fa rro w s , R .
lA-t>, Irwn MiLtichnn i ■! .1 S : К and f r o m LJ-лгг L'l .i I '::l t ■1
Лггн-тк.т M kIioj.1 A i i o c i ition. All п-i^hiIt t**ftTicydLl
 ’* 'I , . * # V -
Л. t *■ * / « . 4 * - *
5*. V r • s « --Г-
‘> V 'V J * 4 . - -
> * :> f w ♦ * j £ . .

г‘ Г г f
I г 4 ^ v r
* _ ^ lF # V
RETINAL TELANGIECTASIS AND
ARTERIOVENOUS ANEURYSM
itelinal lebmgi ectasias, jimcrm'essels. arteriovencHiS aneu­
rysms. and arteriovenous communications are nol true
tumors and are discussed in Chapter ft.
I 3 .2 3 R e tin a E c a p i l l a r y h e m a n g i o m a I r e a l e d w i l h
p h o to d y n a m ic th e ra p y .
A - F : А 2 0 - y e a r-o ld m i n w ill? s o lita rv rtitinal c a p illa ry h e m ­
a n g io m a w ith e x te n s iv e e K u d a lio n in v o lv in g Lbe m a c u la
iA Find B ). In audition- lo the h e m rm g io m a [h e re Fire several
sm all m iCrtjan^lJrybrns b e y o n d the lu m o r suggesting a s s o c i­
a te d retinal te la n g ie c ta s ia . In a d d il io n lo Lhe tu m o r v a s c u la ­
ture fillin g u p . flu o re s c e in a n g io g ra m s h o w s d ila te d c a p illa ry
lii 1 1 :■■■i : I: i.■г■11 i- ui| км l \ i ■и a n d m ic ro a n e u ry s m s . SLiLj^csl-
rng associated C o a t s '- 1ike v a s c u la r пга Iform a Li o n I C l. F a m ily
h islo ry, sys le m ic e v a lu a t io n a n d g e n e tic testing w e r e n e g a ­
tive lo r V o n H i p p e l - L i n d a u d ise ase. N o te s h rin k a g e a n d
gliosis w iLh re s o lu tio n ot" s-ubrcliгьдI flu id a n d h a rd lip id e x u -
Н л Ii(3n 3 m o n th s fo llo w in g Ire a tm e n l w ith a s in g le session o f
s la n d a rd -flu e n c e p h o lo d y n a m iL th e ra p y lE a n d F).
C - M : A 76 -y e a r-o ld w o m a n was ofiS^firad for at leasl T O
yiears for a "retinal lesion ." H e r vis io n d ecrea sed Lo 2 0 / 3 0 - in
Lhi-s eyu a n d a FEV F s h o w e d paracenlial s c o to m a . A sl-mwfjerrv-
shaped c a p illa ry h e m a n g io m a w a s seen o b s c u rin g m usL o f
Lhe o p tic disc i C a n d H l A n g io g ra m s h a v e d Lbat lb e vessels
w iLb in lbe m ass iilk 'd a n d lea ked m ild ly., a p p e a rin g lik e a
s m o k e s La tk e m a n a tin g fro m the s u p e rio r M e o l the Lu m or (lj.
T h e re w e re lip id e xud aLes in fe rio r to tbe disc that e x te n d e d
Lo the fo v e a . O p t ic a l c o h e re n c e Lom<jgr;-iphv re v e a le d cystic
s w e llin g o f Lbe in n e r relina in Ihe v ic in ity o f the tu m o r (|1 a n d
m ild th ic k e n in g o f lb e Eovea I k ;. S h e b a d n o fa m ily h istory
suggestive o f v o n H ip p e l - L i n d a u a n d ^ e n e le s lin g fq f v o n
H ip p e l- L in d a u re tu rn e d n e g a tive . She u n d e rw e n t a re d u c e d -
П и Ё п № p h o to d y n a m ic ih e ra p y , w h ic h s h ra n k the tu m o r
c o n s id e ra b ly lo reveal the u n d e rly in g o p lic disc ;L l r lip id e x u ­
dates g ra d u a lly d is a p p e a re d , a n d the fo v e a I cysts re s o lve d .
H e r vis io n re m a in e d at 2 W 3 0 eccen Lrica 11y. H o w e v e r , Lhe
lesion re g a in e d s o m e s ize at 1 3 -m o n lli fo lk *w -u p -.Vl)f a n d il
has re m a in e d s ta b le s t .1 y e a r s .T h e vis io n re tu rn e d to 2(1/20.
VASOPROLIFERATIVE RETINAL
TUMOR (REACTIVE RETINAL
VASCULAR PROLIFERATION)
ihere may be some difficulty in differentiating peripheral
exophytic angiomas from relinal telangiectasis or pseudo-
angiomatous masses caused by reactive vascular prolifera­
tion in patients with retinopathy of prematurity, branch
vein occlusion, diabetic retinopathy familial exudative
vitreoretinopathy, pars planitis., X-l inked juv^tfle rt’tino-
schisis, chronic rhegmatogenous retinal detachment, and
retinitis proliferans [Figures i^ iij- L a n d
Vasoprolit'eralFve lumor,
A 1 5 -ye a г-u ld fe m a le W ith neuiufi-brom aLcjsiH lv p e -1 Wris
referred Гог e v a lu a tio n or" painless floa ters in h e r riyh l e ye
rjt 1 m u n lh 'f; d u ra tio n . V is iu n w as a b s e n c e o f light p e rc e p ­
tion in [he JefL e ye ль л Tes-ull o f н lefl o p tic n e rv e g lio m a
lhat h a d h e e n trea ted w ith c h e m o th e r a p y . In the righL e ve .
visual a c u ity w as 20 /i 0 Lind intra<n:ular p rt's su je N O V I W as
12 m m K g . A n le rio r-s e g m o n l e x a m ii:a lio n ie v e a le d n ilm e W iJs
isch n o d u le s , flo rid ^ e o v a s ^ ta liiiia titJn o f Lhe iris, a r d i f ) 0 °
net)v a s c H lari z a tio n o f I b t anj^le 'A . IJila tcid Fu n d u s c x n m i,-
naLion o f the right e v e re v e a le d I-2 H - a n te rio r v ilre o u s cells
a lid ал in te rio rly lo c a te d p in k , d e b a te d v a s c u la r m ass w ill:
areas ol s u rro u n d in g s u b re lin a l fluid a n d lip id a c c u m u la tio n
iB j. D ila te d to rtu o u s fe e d e r vessels, as seen w ilh retinal c a p ­
illary h e m a n g io m a , w w e noL u h s e rv e d . T h e paLient had j lis-L
c o m p le te d a la p e rin g co u rse o f ига I steroids (starting d o s e 6 0
m g Q L i . ta p e re d Lny 2 0 rrrgAvepicj that h a d b een p re s c rib e d
b'. Ih e re fe rrin g physician^ Sa lien t wan IreaLed w ilh dciuble
fr c e jc -L h a w 1 ran s c u n ju n c Iival c ry o th e ra p y a n d s im u lta n e o u s
in :-, i■■.i Ire . 1 I i n j i4 ti( i-г о N jc v .it j. u m a b ■ 1.1 5 11 -g m ■: . : " i : I ■.
О л е w e e k later, lh e N V I w a s n e a rly c o m p le te ly Fe sp lve d
a n d Ih e I G K w a s 1 3 m m H g . O n e m o n Lh after tre a tm e n l Lhe
retinal d e ta c h m e n L o v e rly in g (h e vaso p n o lite rative [и п ю г h a d
ffis q lye d nmd lb e tu m o r a p p e a le d less v-asciilar w ith Fibrfltie
t h a n g e s. A s e c o n d jtije d tio n o f in I rav il refi I b e v a c iza m r ib
was g i w n fcx persistent N V I . O v e r Lhe co u rse o f the ntmt (»
m o n th s the N V I re s o lve d a n d the lu m e n U n d e rw e n t fib ro tic
chanjjes w ith c h o rio re lin a l a lro p h y a n d h y p e r p ig m e n ta lio n aL
the p o s te rio r m a rg in (C ^ A1 36 m o n th s a fte r initia l tr e a tm e n t
c lin ic n l fin d in g s w e re stab le , w ith vis io n o f 2 0 .\ !0 .
ll-шт l£ui:(i" t:l wilh pcrrrtiiiicifL
LEUKEMIC RETINOPATHY AND
OPTEC NEUROPATHY
loss of central vision in patients wilh either acute or
chronic leukemia may he caused either by direct leukemic
invasion of the i№ al trad, retina, vitreous. or oplic nerve
or by other associated hematologic abnormalilies, includ­
ing anemia and hyperviscosity or a combination of both.
Previous studies have described an overall ocular involve­
ment in 3-90% of cases based on clinical examination or
autopsy Л figure of about 40% based on
prospective clinical studies is more realistic."4,1:1"°,J However
previously published reports have been biased towards
acute leukemia, suggesting that ocular involvement in more
common chronic leukemia is infrequent.261^™
Leukemic Retinopathy
lhe most striking fundus pictures associated wilh leuke­
mia involve the relina and they typically occur in patients
wilh acule leukemia, frequently during a period of relapse
and frequently associated with severe and coexisting
anemia (Figure ]3.2?>}_l'"::'“,ac' " 11 JM I'hese patients may
develop dilation, tortuosity, and beading of the retinal
wins; relinal vascular sheathing; cotlon-wool patches;
superficial flame-shaped hemorrhages; deep, round hem­
orrhages; wbite^entered hemorrhages; and subhya-
Loid and subin tern aI limiting membrane hemorrhages
(Figure 13.25). I ’hese changes are similar to those seen
in patients wilh severe anemia from any cause as well as
dysproleinemias (see Figure Some
palients may develop grayish-white nodular leukemic
retinal infiltrations and perivascular retinal infiltration
I i .l Я Hemorrhagiс relinopathy associated with acute
leukemia.
A -E : This man wilh acule m yelogenous leukemia developed
bilateral Joss of vision. Five months IлLut afIот £hem othe$ipy
tjfc vision had improved and there was nhark&d iinpruvumr'nl
in lbe retinopathy.
F —H : Tin is m a n w ith acu te ly m p h a tic le u k e m ia e x p e rie n c e d
b ila te ra l loss, o f v is io n . N o t e the w h ite -c e n te re d h e m o rrh a g e s
a n d s u p e rfic ia l Telinal h e m a to m a ''arrijw , Ci-.
1 a n d J : B e fo re d e a th this p a l ienl w ith Lh ru r *iс gran-ulotiyLic
Fe u ke m ia h a d e x Le n s iv e p w iv a s c u la r in filtra tio n a n d n o d u la r
w h ile a n d ЬегйВЬгЙЪад^ m assfe* in lh e re tin a . H is lo p a lb o lo ^ jt
e x a m in a tio n o f lh e eyes re v e a le d m assive p e riva sc u la r le u k e ­
m ic in til I rat io n anrl h e m o rrh a g ic n o d u la r le u k c m ic lu m e fa c -
LioTTb ly in g b e n e a lb ifie linltirnEil lim iLin g m e m b r a n e (a rrc w i.
il-rum K u w .ilk ir.L et ,lI : ' 1 № 4 . A n iLvic .l ii V ,L4 Jk .,il A ^ t K ' . i iiu ii. A il ri^ h l1-
(Figure l3.26),2a<lJJ5 Patients, particularly with chronic
myelogenous leukemia, may develop peripheral retinal
microaneuiysrns,27;'-Jfl6 retinal vascular closure,2w' and
retinal and oplic disc neovascu]arizallon.::<'< ' j!,17,-i0|-,":""
Increased blood viscosity and reduced blood flow associ­
ated wilh prolonged and marked leukocyt^ls^^^^^'^^3
and thrombocytosis "'' are probably the cause of these lat-
Ler changes. Fluorescein angiography is helpful in detect­
ing these alterations, l.eopard-spot 1?E*E: alterations seen
tn these patients, often during the stage of remission, are
probably caused by choroidal infiltration [E'igure 13.27
G - l)/ -'*""'-
" ■ ' Tigmenl epithelial and retinal degenera­
tion may occur in one or bolh eyes and occasionally may
be accompanied by development of a macular hole." 1"■'l:
Leukemic Optic Neuropathy
Acute visual loss may be caused by leukemic invasion of
the optic nerve, usually in children with acute lymphocytic
leukemia (E'igures 11;1бА-5 and 13.28A and Ji}.. In some
patients the infiltration may be confined to the retrobulbar
area or may involve the optic nerve h^lt-ifS'ig7_-3Dl Visual
loss 1[i these 3alter patients may be minimal, and the swol-
Een oplic nerve may be mistaken for papilledema associ­
ated with increased intracranial pressure (E:igure 13.2SA).
Jhese patients show a dramatic response lo aiuimetabo-
Eile, corticosteroid, or oibilal irradiation therapy. which
should be instituted promptly after a Cl- study and lum­
bar puncture to exclude papilledem a.Infiltration of
the optic nerve may be associated with occlusion of the
central retinal artery (Figure ]3.2SC-]E) and vein.-1'1'-30*
Progressive visual Joss anti oplic atrophy may occasionally
occur coincident with a worsening of chronic lymphocytic
letdflftriUa™ or blast crisis in chronic myeloid leukemia
(Figure I3.2SE-K).
Leukemic Infiltration of the Vitreous
An occasional patient with acute leukemia may lose
vision because of vitreous cellular in filtration, and vitrec­
tomy may be of value in making the diagnosis as well as
improving the vision.^7’5 Other unusual causes of visual
Loss in patients with leukemia include iris infiltration.305
anterior-st.'gmenl ischemia,-1' ' open-angje glaucoma,,u"
and cornea! ring ulcer.-ео
I L e u k e m ic infiltration o f th e retina a n d o p tic
nerve.
A-F: Th is 6 -v e a r-u ld girl d e v e lo p e d ly m p h o c y tic le u k e m ia
rn D e c e m b e r 39 6 6 . S h e w a s H e a le d w ith v in c ris tin e , p re d ­
n is o n e , and I'netfSptrE&atE. EJecauire o f via uni loss s h e w a s
seen at the B a s c o m F u lm e r t y e Institute o n N o v e m b e r fl,
1 9 6 7 . V isu a l a c u ity in th e rig h t e ye w a s Finger c o u n tin g a n d
in Ihe left e ye w a s h a n d m o v e m e n ts . T h e optic n e rv e b e n d in
b a lb eyes w a s o b s c u re d b y a m a s s iv e c e llu la r in filtra tio n that
e x te n d e d inld llte retina in lh e p e r ip a p illa r y re g io n ' A Lind li:.
T h e n : W as p r o n o u n c e d p u rivu n o u H in filtra tio n . E3v D e c e m b e r
3r 1 9 6 7 , Lhe d e g re e of in filtra tio n in the rig h t f-Ve h a d
im p ro v e d (C ) . T h e r e w a s fu rth e r im p r o v e m e n I b y M a r c h 1 3 ,
19 6 & I D ) . O i : |u n e 1 1 , 1 9 6 d , heir vis u n l a c u ity h a d rriu rn c tJ
to 20-'20 in this e y e . B y M oVE.m bfer 1 4 , T 9 6 E , the p n lie n t w a s
q u ite w e ll a n d w a s a lle n d in g s c h o o l. H e r v is io n in the right
e ve w a s 2 0 / 2 0 . M u s t o l Ihe p e riv a s c u la r in filtra tio n h a d d is -
лррс*атсч] '.fcj. T h e o p lic n e rv e h e a d w a s p n le , nrnl Пн m arg in s
w e re b lu rr e d . T h e v is u a l a c u ity in the Eeft e y e w a s 2 0 /2 0 0 .
a n d th e re w a s still e v id e n c e o f p e riva sc u la r in filtra tio n (F ).
C —|: L e u k e m ic in filtra tio n o f Ih e re tin a . Th is E -y e a r -o ld girl
w ith a c u te le u k e m ia d e v e lo p e d loss o f cenLral vis io n in Lhe
left e y e . The o p Lic n u rve bend w n s b lu rr e d , a n d th e re w e re
KCrillered retinal h e m o rrh a g e s in th e m a c u la a n d e ls o w h e je
in th e fu n d u s (£.)_ In Ihe p e r ip h e ry th e re w a s p r o n o u n c e d
p e riv a s c u Ini s h e n lh in g , prenun'jed to b e s e c o n d a ry to le u k e ­
m ic in fil trill io n 'H j . Flu o re s c e in n n g itjg jn p h v re ve a le d d ila ­
tion Lind m ic ro n па и rvsm n I fo rm a tio n in lh e retinal c a p illa ry
b e d a n d w id e s p re a d le a k a g e o f d ye fro m th e c a p illa rie s a n d
ve in s 11 a n d I
f 'i ,2 7 L e u I t e m iс r e t r n n p a l h y .

Л - F : rlus г е - у е а г - ^ И A fr ic a n A r t fe r it a r m a le W o k e up w ilh
s udd u n baiflless 1оыы a vis io n in b o lh evns Ю ha n d m o lio n .
H u hfid m ild p u ls n lin ^ e ye p a in ^ la te ra lly . Th e antericur seg­
m en t w as q u ie t. T tie right e y e re ve a le d m a s s ive retinal, prereLi-
п л I, a n d 5ubrLlina3 h e m o rrh a g e s in lh e posterior p o le ' : А - Г : .
lh e fflid-rfltina m o w e d largelliku in lr» гч^И п-л I Ь е т о [^ т5 Ю в
w ilh w h ile iceqfej. Flu o re s c e in a n g io g ra m re ve a le d b lo c k a g e
□E ch oroFd a l fluorescentDe fro m Lhe b lo o d (L>>. H is la b o ra to ry
investigations re v e a le d h e n n k>I o b i n ol 3 .4 w ith a h e m a to c rit
□I 9 .6 , a platelet c o u n t o f 4 0 0 D f a n d a w h ile b lo o d cell c o u n t
fif 4 0 0 0 r suggesting severe p a n c y to p e n ia . C o m p u t e d to m o g ra ­
ph y o f the hend wan n o rm a l. B o n e m a r ro w b io p s y c o n firm e d
acu te ly m p h o c y tic le u k e m ia o f T-cell lin e a g e . H e w a s treated
w ilh intrathecal m e th o tre xa te w e e k ly , v irltrliftin e , b -lh io g u a -
n in e , a n d B a c trim and rece ive d several b lo o d transfusions
a n d platelet transfusions. The^visufll a c u ity im p ro v e d to 20.S50
in the right e y e a n d 2 0 /3 0 0 in the lefl e y e . T w o m o n th s later
h e m o rrh a g e s resolved w ilh soin-e p a llo r Lo the optic d is c rind
residual fiagfhentary cha ng es in the m n c u Li ; L , F ).

^.'■uurCL-sy a t L)r. VVi^li.im -Miultir.p

'[ i . 2 У L e u k e m i c infillratiun o f th e o p lic n e rv e ,

A a n d B : This 6 -y e a r-o ld girl d e v e lo p e d le u k e m ic Lra n sfo rm a -

Иол o f a I у m p h o s a гсогпл o f Сhe m udi asLinu n’t. In- lunr1 1 9 7 0
she w b s treated w ith a r ^ i n t H i o f v in c ris tin e , nw tbotreK aLe^
a n d p re d n is o n e . Rf?m Vision w a s a c b ie v ^ p r b u l by S e p te m b e r
Lhe c h ild d e v e lo p e d signs a n d s y m p to m s o f cenLral n e rvo u s
s y s lfm k w o Jv e m e n L . In lra tfia jlil (jjie Lh a ta x a le w a s g iv e n on
S c p le m b e r i r 1 4 7 0 . О л S e p te m b e r 1 0 , 1 970 , her KS^jon in
lh e right e y e w a s lig b l p e r c e p lio n w ith p r o je c tio n a n d lh e
left e y e w as 2 0 ^ 2 0 . I lie righL O p tic nttrve h e a d Lind p e r ip a p il­
lary relin a (K1 w e re s w o lle n a n d w h ile in c o lo r. Th is w a s p re ­
s u m e d to be related lo le u k e m ic in filtra tio n . T h e o p lic d is c in
Lhe left e ye w a s n o r m a l. A s u b c o n iLu ic liv a l in je c lio n o f tria m ­
c in o lo n e w a s j^ivcn.. a n d a c o u rs e o f oral p re d n fs o n e , 2 0 m g
ihree Lim es p e r d a yr wan b e g u n . O n O c to b e r- 1 5 . 1 HJ 7 0 vis u a l
a c u ily w a s 2 0 ! J O in each e y e . T h e s w e llin g o f the ril;h I o p Ljc
disc h a d la rg e ly d is a p p e a re d 1 L I. T h e re w as toss o f p ig m e n t
fro m the relin a l p ig m e n l e p ith e liu m associated w ilh m u llip Je
b la c k c lu m p s o f p i r a t e п I h u iro u n d in g lh e o p lic d is c . H e r
general c o n d i Li o n d e te rio rate d .. a n d she d ie d on U e c e m b e r
2 7 , \9 70 .
C —H i Th is 3 7 -y e a r -o ld m a le w it h T-c e ll a c u te ly m p h o c y tic
le u k e m ia , d ia g n o s e d 6 m o n th s e a rlie r, h a d re c e iv e d five
cycle s o l b yp e rc ел I ral v e n o u s access d a y fe e c h e m o th e ra p y
that co n siste d o f c y c lo p h o s p h a m id e , v in c ris lin e , A d ria m y c in ^
a n d d a u n o r u b ic in 4 rTiqflths a g o . H b h a d suffere d s u d ­
d e n loss o f v is io n in his rig h t e y e & d a ys p re v io u s ly lh a l b e
desc rib e d as "v is io n w ilh d a rk bunjilasses" lh al w a s inLerm iL-
Lenl fo r л d a v , Ih e n № ir tiln e d p e r m a n e n tly d a rk thereafter.
H e h a d a s im ila r e p is o d e in lh e lefl e y e -1 m o n th s p re v io u s ly
a n d d id noL re c o ve r v is io n . H e re c e ive d im ra v e n o u s steroids
b u! o p h th a lm ic . e x a m in a lio n w as noL s u u g h L. H is v is io n w a s
fight p e r r e p lio n o n the rig h t a n d n o lighL p e rc e p tio n on Lbe
le ft T h e u p t k n e rv e w a s p a le a n d s w o lle n w it h p e rip a p illa ry
a n d m a c u la r w h ite n in g , c h e rry -re d spot a n d b o K c a jrin g o f
Lhe b lo o d c o lu m n in Lbe a rleries. T h e re w e re several retinal
h e m o rrh a g e s in lh e p o s te rio r p o le i C - E l . I h e lefL o p lic n e rv e
was pale a n d t u p p e d w i lh a n аг1ету-1о-л г1егу c o lla te ra l s u p e ­
rior Iо Lhe day.'. A flu orescein a n g io g ra m re v e a le d a lm o s t л о
b i(K )d flov. th ro u g h :1ч 1 lu n c h e s >f Lbe cenlral retinal arlury
at Ihe disc b o lh e a rly a n d late a n d H j . H e re c e ive d ra d ia ­
tion lo lh e o p tic n e rv e a n d c b e m o lh e ra p y v ia an O m m a y a
reservoir, b u l his visi-on d id n o l im p rijv e .
I-К: T h is 2 0 -y e a r -o ld m e n ia lly c h a lle n g e d m a le w ith c h ro n ic
m y e lo id le u k e m ia w e n t into bias! crisis a n d n o te d loss o f
vis io n m b o lh e y e s. The l-efl e y e h a d a d e n se vitre o u s h e m ­
o rrh a g e w h ile lh e rig b l e y e had le u k e m ic in frlLra iio n o f Lhe
o p lic n e rv e (H . H e re c e ive d 2 4 G y e x L e m a I-b e a m ra d ia tio n
Lo b o th o rb ils o v e r 2 .5 w e e k s . Ih e in fi Urates Ib in n e d o u l o v e r
Й w e e k s LJ an ti K i b ul v is io n d id not im p ro v e s u b je c tiv e ly . An
a ccu ra te assessm ent o f his vis u a l a c u ily c o u ld not b e m a d e
d u e to his m e n ia l staLus.

'I-К... l o u r l / j v , i г I 'Ч Ir jn c o K l ' l c Ii i -

VITREORETINAL LYMPHOMAS \ Diagram illustrating the pathologic anatomy
underlying the variety o f clinical pictures caused by
b e n ig n re a c tiv e ly m p h o id h y p e rp la s ia o f lh e u v e a l tract t h e ocular-central nervous system form o f la r y e - cel I

Lin d u v e a l l y m p h o m a a re d is c u s s e d in C h a p t e r 1 4 .
non-Hodgkin's lymphoma.

Lymphoma te lls infilLmle [he i/ttreous (small Lirrow, A. and

Ihe sub-reli^hl piemen! cpilhelium -KPbi Б р аф <ird product:

Primary Central Nervous System in ilia IIу small pfacbtd lesions IsJbrmiljlE ing mu Ili pie earnest ел I
while-doL syndrome, alightly el twilled Зеиипк iBj sirmjladjjtig
Lymphoma (PCNSLj ' m u11i ГосгТI tboroidiliH. or larger sub-hi PL- rriLisses (Ci lliat tire
р^6ЬпугОггк:п1с fur non-Hodgkin's KmphuniLi. Invasion of
Л la rg e B - c e l E n o n - H o d g ) t l n ri В l y m p h o m a m a y a rise p ri-
the overlying n.'tina (Ej produces \vhile lesions simulLilin^
m a r i l v in t h e C N S , in c lu d in g th e b ra in , s p in a l c o rd , a n d
ncule retinitis, and ischemic retinal Fnfatction. As these reti­
m e n i n g e s . In a s u b s e t o f p a tie n ts , l y m p h o m a m a y b e c o n ­ nal lesions expand lbuy niLiy irtVa.de and occlude jelinal ves­
fin e d to v itre o u s /R E:h /re tin a - s o -c a lle d P C N 'S L - O V a ri- sels and produce a clinical pjclutJe of acuLe relinal nGCrdsi}.
a n t . ' ^ 0, : ' H. is e s t i m a t e d t h a t P C N S I . - O re p re se n ts 1% of 5ponlaneous necrosis and resol u1ion o f I be lym phom a mny
non -1 l o d g k i n ' s l y m p h o m a .. o f in tra c ra n ia l t u m o r s , a n d occur early II» . and produce mu ILi foe a I chojiorelinal scars
f a r [e s s t h a n 1% o f in lra o c u la r t u m o r s . T h e re is a h u n - simulating the presumed ocular histoplasmosis syndrome, or
La I и !H, Lind cause large geographic ar£as or diffuse areas of
d a n t e v i d e n c e t h a t t h e i n c i d e n c e o f t h i s t u m o r is i n c r e a s ­
HF’b alrophy slrrulaling de^tmer.nive and poMinllammatory
i n g .',-1 . A c c o r d i n g t o N a t i o n a l C a n c e r I n s t i t u t e S u r v e i l l a n c e . .
s e in in g .
E p id e m io lo g y , and Iin d R e su lts [S E E R ) d a tab a se , th e
in c id e n c e o f P C N S 1 . rose f r o m 0 .2 7 per m illio n in 1 9 7 .1
to 3 0 .0 p e r m i l l i o n in th e e a rly 1 9 У Os, in d ic a t in g a m o r e
L h a n 3 0 - f o l d i n c r e a s e i n t h e t h r e e d e c a d e s . 4 24 11 ' ' l h e m a in (h e b io m ic n o s c o p ic c lu e Lo t h e s u b -R P H lo c a tio n o f th e
c a u s e o f t h e i n c r e a s e d i n c i d e n c e o f P C M S I . is a r i s e i n p r e v ­ tu m o rs , w h ic h m a y be c o n flu e n t a n d m a s s iv e in s ize . ' I h e
a le n c e o f im m u n o d e f i c i e n c y , a c q u ir e d im m u n o d e fic ie n c y tu m o r m ay e xte n d th ro u g h th e JtP L in to th e o v e rly in g
s y n d ro m e ( A I D S ) , and im m u n o s u p p re s s io n .-^2 sen sory re tin a and v itre o u s , w h ere it p roduces a lo c a l­
In p a tie n ts p re s e n tin g w ith P C N S L-O , C N S in vo lv e ­ i z e d w h i l e Ee s io n l h a l m a y s i m u l a t e t h a t o f a c u te re tin itis
m e n t w ill a p p e a r in 5 0 - 8 0 % o f p a tie n ts several years a fte r (I'ig u r e s 1 3 . 2 9 El , 1 3 ,3 0 1 , a n d 1 3 .3 1 C and E-IJ. in filtra tio n
t h e o n s e t o f o c u l a r s y m p t o m s .-11 ■ " l|:: C o n v e r s e l y , 15 -3 ^ 5 % o f t h e m a j o r r e t in a l ve sse ls m a y c a u s e a f u n d u s p ic t u r e o f
o f p a tie n ts w ith E1C N S [ . h a ve o c u la r in v o lv e m e n t at th e branch a rte ria l o c c l u s i o n fi'ig u r e 1 3 .3 1 C - L ) , and h e m o r­
L i m e o f d i a g n o s i s o f P C № S i *311,31 J A p p r o x i m a t e l y 2 !> % o f rh a g ic in fa r c tio n o f th e re tin a s im u la tin g th a t seen in a c u le
PC N S L p a tie n ts w i t h o u t o c u la r in v o lv e m e n t W ill d e v e lo p re tin a l n e c ro s is caused by th e h e rp e tic viru s e s [E 'ig u r e
in tr a o c u la r l y m p h o m a .na 1 3 . 3 2 1 - K ) . ::^ !-" : An o c c a s io n a l p a tie n t pre se n ts w ith
P a tie n ts are u s u a l l y in th e s ix th to S e ve n th decade of v is u a l lo ss caused by ly m p h o m a to u s in filtra tio n o f th e
life w h e n t h e y p re s e n L t o lh e o p h t h a l m o l o g i s t w i t h a w i d e re tFo b u lb a r p o r tio n o f th e o p tic nerve s im u la tin g re tro b u l­
v a rie ty o f c lin ic a l p ic tu re s th at m ay s im u la te m any ocu- b a r n e u ritis o r in filtr a tio n o f th e o p tic n e r v e h e a d s im u la t ­
Ear d is o rd e rs (fig u re s 1 3 .2 ^ - 1 3 .3 2 ) . Young a d u lts and i n g p a p i l l i t i s .1- ^ " '- '1 ,'l h e d is e a s e b e c o m e s b ila te r a l in 8 0 ^ b
c h ild re n are o c c a s io n a lly a f f e c t e d .-*1 -1 ' I h e o c u la r-C N S o f th e cases. There m a y b e a d e k iy o f m o n th s o r several
fo rm o f la r ^ e c e ll ly m p h o m a m ost fre q u e n tly m asquer­ ye a rs u n t il i n v o l v e m e n t o f th e s e c o n d e ye . Irid o c y c litis a n d
a d e s as p o s te r io r u v e itis i n p a tie n ts c o m p l a i n i n g o f flo a t­ se c o n d a ry g la u c o m a m a y o c c u r la te r in th e c o u rs e o f th e
ers c a u s e d b y t h e v i t r e o u s i n f i l t r a t i o n w i t h l y m p h o m a t o u s d ise a se . I n s o m e p a tie n ts th e re is a r e m a r k a b l e t e n d e n c y
and in fla m m a to ry c e lls. M ost o f th e p a tie n ts w ith v itre ­ fo r th e s u b p ig m e n t e p ith e lia l le s io n s lo re s o lve sp o n ta ­
ous in filtra tio n w ill soon a fte rw a rd d e v e lo p m u ltip le n e o u s ly. W hen th is occurs e a rly m u lLifo c a l s m a ll scars
fu n d u s le s io n s ., w h i c h in iiia llv m ay be n o n e le va te d and s im u la tin g lh a l in lh e presu m ed o c u la r h is to p la s m o s is
a p p e a r s im ila r to m u ltifo c a l c h o ro id itis ( i'ig u r e s 1 3 .3 ]С syn d rom e occur (I'ig u r e s 1 3 .2 9 D and 1 3 . 3 1 Ci 1. W hen
and 1 3 .3 2 G , II, and LJ o r m u ltip le evanescent w h ile -d o t la rg e le s io n s re s o lv e , la rg e fo c i o f g e o g r a p h ic a tro p h y o f
syn dro m e ( E 'ig u r e 1 3 .3 1 A )., b u t w h i c h ty p ic a lly e n la rg e to ( h e p i g m e n t e p i t h e l i u m m a y s i m u l a t e l h a l s e e n in d e g e n ­
fo rm s o lit a r y , s h a r p l y d e f i n e d , b l i s t e r !ike . y e l l o w i s h - w h i t e e ra tive o r p o s l i n f l a m m a t o r y d is o r d e r s ( f ig u r e s 1 3 .2 9 3 : a n d
s u b - R P L t u m o r s th a t are u s u a lly s u ffic ie n tly c h a ra c te ris tic 1 3 .3 0 P ) . W hen p re se n t, th e m u llip le s o lid R PJi m asses
to p e rm it an a c cu rate d ia g n o s is (fig u re s 1 3 .2 У С , 1 3 .3 0 , are v ir tu a lly p a t h o g n o m o n i c f o r t a r jg e c e l l l y m p h o m a . - 1'''-
and 1 3 .3 1 1 3 ) .'- 'lh e fin e s p e c k lin g o f p ig m e n t O c u la r s ig n 5 a n d s y m p to m s u s u a lly a n le d a le th o s e caused
on t h e s u rfa c e o f ih e s c a m e ! a n o li с s u b re tin a l m ounds is b y C N S in v o lv e m e n t.-^
 r Sflcntaneojs
rebdu:icn
RFE

Large sub-RPEluros 0 GeographicR^Eatrophy

 I f l a r g e celL l y m p h o m a is s u s p e c t e d l h e p a t i e n t s h o u l d 13.30. Primary central nervous system lymphoma
have a general m e d ic a l e v a lu a tio n , in c lu d in g n e u ro lo g ic confined to v ilreous.;retinal pigment epithelium (KPE)/
e xa m in a tio n , M R] scan, and lu m b a r p u n c tu re . In m ost retina (PCMS-О lymphoma).
cases th is e v a lu a tio n w ill b e n e g a tiv e . E x a m i n a t i o n o f th e
A—H: This 60-year-oLd wom an was seen in Decem ber 196S
c e re b ro s p in a l flu id in som e p a lie n Ls m ay d e m o n s tra te with widespread jjfeaS B# solid yellow-w hile detachmunis of
Ly m p h o c y to s is but in fre q u e n tly d e m o n s tra te s th e pres­ lhe KH'E in tier left eye iA, K, anti 1J). Angioj'NiptiLcailv these
ence o f m a lig n a n t c e lls. V i t r e o u s b io p s y m ay be neces­ EesIdts w ere largely nonfluonescent (Cl. M edical evaluation
sary to c o n fir m th e d ia g n o s is . T h is s h o u ld be d o n e was negative. These lesions disappeared spontaneously and
Ihe patient had 2(V2t> visron 4El. W h en she nilum ed 4 years
o n ly when a n e xp e rie n c e d te am fo r c y to lo g ic e v a lu a tio n
1.1 1ci г there were widespread FIL’E atrophic changes in the lefl
is a v a i E a b l e . live n u n d e r th e best o f c irc u m s ta n c e s , a fte r
eye. In the rijjht eye she had the same picture, illustrated
o b ta in in g th e v itre o u s s p e c im e n , p ro p e r c o n c e n tra tin g a n d
in the left eve in D. Ten weeks later she died after experi­
s t a i n i n g o f t h e v i t r e o u s ce lls, a n d e x a m i n a t i o n b y a s k ille d encing jacksonian tei/ufes. Croiis gJcanj inatiori of Lhe righl
c y to lo g is t, a d e fin itiv e d ia g n o s is m a y n o t b e p o s s ib le . In eye revealed mullipEe necroiic w hile Lumors benealh Ihe
s o m e p a tie n ts c y to lo g ic e x a m in a tio n o f t h e v it r e o u s a sp i­ deLached K P t (arrujws, Fl. N olu dmachment of the Lhinned
ra n t m a y reveal o n l y i n f l a m m a t o r y c e l l s . 153 D i r e c t b i o p s y and clumped REJt (upper armfw, C j and Iiq uetacIive necrosis
of Шгпот between Iht! and viable tumor lying along Ihe
o f t h e c h o r o i d - R P 1 : c o m p l e x in th e area o f a v is ib le le s io n
гпгег surface of Bruch4 membrane (low er arrow, tJ). V iable
o ffe rs th e be st c h a n c e fo r a d e fin itive d ia g n o s is b u t th e
rcliculum cell sflrocma (arrow was lying alony !he inner sur­
p ro c e d u re has a h ig h e r m o r b id ity /^ 1 Jf lh e e v a lu a tio n o f
face of Kruch^ membrane i3-lj. Nole chronic inflammatory
th e p a t ie n t re ve als e v id e n c e o f a C N S le s io n , a C l -g u id e d cells in lhe choroid.
ste re o ta c tic b io p s y is a n e ffe c tive m e a n s o f a rriv in g at a I- К : 5ubpiyment epilhelial lymphoma in a 62-year-oEd man
d i a g n o s i s . ' i '1- U l ) C y t o l o g i c e ita m i n a t i o n is m o r e i m p o r t a n t afler vitrectomy. Note tumor (arrow, I] breaking through the
t h a n l y m p h o c y t e s u rfa c e m a r k e r s in a r r i v i n g at t h e c o rre c t KPE. Vilreous aspirate showed cells w ilh enlarged hyper-
tbromati'c indonled nuclei and minimal cytoplasm |arrow, |J
d ia g n o s is o f la rg e -c e ll l y m p h o m a . 1 '- - ш Irre g u la r n u c le a r
characteristic of reticulum cell sarcoma. Rusolulion of tumor
c o n to u rs . Jo b a tio n of n u c le i, coarse irre g u la r ch rom a­
occurred 3 mondis after exLermiI-beam irradiation (Kj.
tin , a n d th e p re s e n c e o f n u c le o li a re e y to lo g ic fe a tu re s o f
la ig e -c e ll l y m p h o m a ( E 'ig u r e I 3 .3 0 J J . A n c illa r y te c h n iq u e s
IA-K, ■
Mini Ci.Lis(;[ At. )
in c lu d e im m u n o h is to c h e m is try and flo w c y to m e try to
d e te rm in e th e im m u n o p h e n o typ e s o f ly m p h o c yte s , gene
rearran ge m ent s tu d ie s , and m e a su rem en t of in te rle u k in free o f t u m o r b u t is i n f i L t r a t e d w i t h ly m p h o c y te ^ , m o s tly
Le vels. r e a c t i v e 'I' l y m p h o c y t e s . a n d p l a s m a c e lls ( E 'ig u r e L 3 .3 0 1 E).
1 1i s l o p a t h o l o g i c a l l y p a lie n ts w ith o c u la r-C N S Large In som e cases th e tu m o r m ay e xte n d in to th e u nd e r­
ce ll l y m p h o m a t y p i c a l l y s h o w m u lt ip le areas o f l y m p h o - ly in g c h o r o id o r lh e o v e r ly in g re tin a a n d v i t r e o u s (E 'ig u r e
m a t o u s i n f i l t r a t i o n o f t h e s u b - RPE s p a c e [ I ' i g u r e 13.30H— 13 _ 3 lG -L}. |-Lis to p a Lh o lo g ic e xa m in a tio n o f eyes- a fte r
I Lj [л 1^ е le s io n s are c o m p o s e d s p o n ta n e o u s re s o lu tio n o f th e L y m p h o m a sh ow s m u ltip le
p r i m a r i l y o f n e c r o tic t u m o r l h a t is s e p a r a te d f r o m H a tc h 's g e o g r a p h i c a re a s o f H P ! i a t r o p h y o r p t a c o i d d i s c i f o r m scars
m e m b r a n e b y a t h in laye r o f v ia b le h y p e r c h r o m a lic t u m o r th at m a y s im u la te e ith e r p o s l m n a m m a t o iy scars o r a d i f ­
ce lls ( f i g u r e ] 3 . 3 0 t - - E I J . i n m o s t p a t i e n t s t h e u v e a l t r a c t is f u s e c h o r i o r e t i n a l d y X f t r o p h y 3-143'
 M anagem ent o f ETC N 5 L - G w ith o c u la r ra d ia tio n Primary centraE nervous system lymphoma
(4 0 G y in d iv id e d d o s e s ) c o n tr o ls o c u la r in v o lv e m e n t in confined lo vitreous/retinal pigment epithelium (RPE)/
th e m a j o r i t y o f cases, b u t m o s t p ro g re ss Lo d e v e l o p C N S retina (PCNS-O lymphoma}.
d ise a se . because ra d ia tio n th erap y Lo th e b ra in m ay
A -F: This .ifc-year-old wom an nuk'd bftirr^d vision and
have s ig n ific a n t si d e - e f f e c t s its use fo r p ro p h y la x is in floater!; iгг the rigbl eye. Vilrilis and multiple smal ■w h ile or
p a tie n ts w ith o u t p roven C N S in v o lv e m e n t is nol a d v is ­ цгау-whiLe sahretinal Eesiicins cqrifined I d the rij>hl eye were
a b l e . S y s t e m ic t h e r a p y m a y n o t b e s u f f i c i e n t f o r t r e a t m e n t interpreted as m ulliple evanescenl white-doL Syndrome
o f M C N S L - O . ' 11, In tra v itre a l m e th o tre x a te (4 0 O |jg / O .l m l) liirraws. A .. W h e n ex amilted 1 month taler her visual acuity
was 5/200, rij^hl eye, and 20/20, left eye. She had IcjpEMJ
g ive n over a p e rio d of ] year a c c o rd in g lo a sta n d a rd
a sub-KPE mass 'arrow, Kj and a Swiss cheeselifbe subretinal
in d u c t L o n -c o n s o lid a lio n -m a in le n a n c e re g im e n appears
infillr-Hion in lhe i iцhI eye. Ang&^fljraphy showed evidence of
Lo p r o v i d e e x c e lle n t c o n t r o l ra te s w i t h m i n i m a l to x ic ity .''" 1 ' FiPt changes centrally at well as staining in lhe area ot" Lhe
In tra v itre a l in je c tio n s o f r it m J r n a b (a n li-C D 20 a n tib o d y ; tnfilIrate. The right eye was normal. The diagnosis was large­
1 m g / O . t n i l ) a r e u n d e r L n V ^ s t i g a t i O r L 3^3 "50 cell Lymphoma with probable involvement of the retrobulbar
Kor C N S in v o lv e m e n t, h ig h -d o s e m e th o tre x a te is u s u ­ oplic легче. M e d ical evaluation was negative. Four months
a lly c o n s id e r e d .'' 1 A s t h e b l o o d - b r a i n b a r r i e r is a l i m i t ­ Ial or lhe tumor had resolved temporally but had extended
nasaEEy ItlJ. Repealed evaluations feu evidence of lym phom a
i n g fa c to r l h a l re stric ts d r u g e n t r y i n t o t h e C N S , in tr a th e c a l
were negative. She refused viLneous biopsy. The lesions in Lhe
d r u g d e liv e ry , in tr a v e n tr ic u la r d r u g d e liv e r y b y a re s e rvo ir,
right eye resolved spontaneously and over lhe subsequent 40
and d is ru p tio n o f th e b lo o d -b ra in b a rrie r w ith m a n n i-
monLhs she developed similar lesions in lhe lefl eye. Vilreous
to l in fu s io n are g e n e ra lly u s e d ."30^153 D i s r u p t i o n o f th e biopsy was positive lor lymphoma. Three years after her
b l o o d - b ra in b a rrie r w ilh m a n n ilo l in fu s io n m a y in a d v e r- onset. of symploms she developed evidence of lymphoma in
L e n lly d is r u p t th e b l o o d - r e L i n a l b a r r ie r c a u s in g rn a c u lo p a - the brain. She received irradiation treatment lo the eyes and
th y (J'ig u r e 1 3 J 2 J . ' " i h e t r e a t m e t i l o f l>C J N S L is e v o l v i n g
brain. W h e n Iasi examined her visual atdfty was 20/200,
iii"il i ■
. ■. '.:i: lefl eye I here v, .i1' 'vidci-p'c.v i i-
w ith in a fr a m e w o rk o f in te rn a tio n a l m u ltid is c ip lin a ry c o l­
dence of degeneration of lhe № E but no evid en ce of tumor
la b o r a tiv e s tu d ie s .
in either eye (E anti 1-'. Five years after her inilia! visit she-
was alive nnd Uimorfree. Forgetful ness and depression were
attributed lo postil radiation c h a n g e .
G-L: This apparently healthy 71-year-oEd wom an developed
a superotempora] btam:h retinal artery occlusion caused
by inlraretinal invasion of a suh-KPE lymphoma in Ihe rijqhI
eyEf 'L i I. At lhe lime o f in ilia 1 presentation she had viLre-
dlis cellular infiltration and multiple atrophic chorioretinal
scars in the right eye. The left eye was normal except for a
single focal scar and lesions in lhe m acula interpreted as
drusen. Six. weeks later the retin-al whitening extended inlo
other quadrants ■I -ti and m ultiple yello w plaques (arntjwsf
had developed in the formally occluded relinal artery.
A ng iogia phica 11у there was evidence of narrowing of Lhe
arlury cabber in Lhe area o f these plaque» I arrows, 1^. She
subsequently developed Lhe tlin jcal picture of acuLe relinal
necrosis and rubeotic glaucom a in Lhe rij=hl eye I hat was
enucleated. HisLopathologic examination revealed large
mounds ot necrotic lymphoma benenlh Ihe KF-1!:, extensive
reliral necrosis, lumor invasion of Lne reLLnal arLuries, and
occlusion o f the artery (arrow, 60 on the optic disc and nar­
rowing of Lhe retinal arLery iairows, Ll by tumor and alh-
eromalous deposits, \1edical evaluation for: other evidence
o f lym phom a w as negative. She developed multiple focal
lesions simulating choroiditis in the lefL eye iji. Note lhal
some were hypofEuorescenl (arro w y |). Fourteen monlhs after
her iniLial presentation she developed hemiparesis and brain
scan evidence o f a lymphoma.
M lj-L, I'rLiril U .H l .lCld l l . L l U t r ' " ! I rJ4 I A jTirjl I L ,111 M u r llL .ll A-SSiM i.L llijn .
ЛИ ri^tib rcserwLl/
Mycosis Fungoides 11.32 Blood-brain barrier disruption macu Jopathy.

A—F: A ЬЬ-year-old Caucasian л о г ш г was diagjiosed with

M y c o s is fu n g o id e s , а m a lig n a nL 1y m p h o m a t o i i s d is e a s e
central nervous system lymphoma after presenting wiLh confu­
d e riv e d fro m E l y m p h o c y t e s , arise s in lh e s k in and m ay
sion and headat he. ih e began blood-brain hairier disruption
be c o n fu s e d w ith p s o ria s is . La le r it m ay in v o lv e o th e r Ltierapy 2 monlhs later and underwent 23 ^balmrarts (divided
b o d y o r g a n s . El i n f r e q u e n t l y a f f e c t s l h e C N S and eye. iflrfq 12 cycles); five were given through the right inlemal
^ I n f i l t r a t i o n o f t h e i r i s /11'6 v i t r e o u s , ^ - 1- 1 5 7 '56* c h o r o id ,^ * canolid aitery, i ihmugh Ihe raft internal carotid arfeiy. and (he
s u b -R P L space, o p tic n e rve , a n d r e t i n a 5^ ' 1й з , з к [1ДЬ
remaining through Ihe vertebral artery system. O ne cycfe was
aborted early after art arterial dissection was seen on angiog­
b e e n re p o rte d .
raphy. Baseline examination revealed best-correded visual
atuilv of 2 0 в 0 in Lhe righl eye and 2С)Й5 jn lhe left eye: tio
Lymphocytic Lymphoma retinal pigmenl epilhefium 'ibTEj changes 'лиге found an fun­
dus examination. The patienl firsl noted visual disturbances ir>
ly m p h o c y tic ly m p h o m a o n ly ra re ly in vo lv e s (h e eye Lhe form of "spots of gray clouds" after lour 1re<ilmunts.' acule
(fig u re ] j . 3 ^ ] - l . ) . ' :<,- sri L e w is a n d C l a r k 1" ' re p o rte d a exacerbations in these subfeiitive visual complaints occurred
during each treatmeil arid then returned Lo baseline. These dis-
p e c u lia r p a tte rn of w id e s p re a d re tin a l in filtra tio n in a
lurbances remained Stable throughout and were still prtsenl 1
4 S -ye a r-o ld w om an w ith a w e ll-d iffe re n tia te d ly m p h o ­
year after completion o f therapy. M acular RPE changes in the
c y tic ly m p h o m a in v o lv in g lh e a b d o m in a l, ce rvic a lr a n d form of speckled hypcrpigmenlaLion w ere lirsL documented
s u b m a n d i b u l a r a re a s . JJe Lin a l i n f i l t r a t i o n c le a r e d w i t h i n I after-completion nl" iherapy, a1 which Limp Ixjsl-Lorrected visual
m o n th fo llo w in g tre a tm e n t w ith c y c lo p h o s p h a m id e . v in ­ atuilv wns 2Q/40, righL ev«, and 2(VjO, lefl eye (A). Humphrey
visual field lcsLing Tevealed an inferior righl-sided homonym(*us
c ris tin e , a n d o ra l p r e d n is o n e .
Eiemianopia secondary Lo I hi1 patient's brain tumqf and a small
paracenLral sfiotoma in lhe righl eye. 1-our monLhs lalur, visual
acuilv was *liib;e in the light eve 1-0/40: and decreased in the
left eye i.JQ/JOO) wilh increasing aLnophv anrl pnoliferalion of (he
KPE noled on clinical examination (B). Fluorescein angiogram
reveal™ bilateral early focal hyperflilliltescaicS which fades I in
late phase and focal hypofluoresoence in 1he maculas ft , J?:.
Optical coherence LomogTaphy was consislenl v/iLh mild tys-
Loirf macular edema iit the righl eye and irregular thickening of
Lhe Kt-’E in Lhe lefl eye (I. F:.

Primary central nervous system lymphoma con tine d to

vitreous/RPE/relina (PCNS-O lymphoma} lymphoma
simulating multifocal choroiditis and acute retinal
necrosis,
C -L: This 53-yea r-oJd male was otiservctd for gradual onset; of
Eow-griide vilreous cells and a Jew deep flat cboroicbl lesions
over 9 monLhs in his righl eye. He became svmptomalic v’.i 11:
floaters and photopsias when the vitreous cells increased.
At lhal time he was noled to have in addilion a few flat new
d w p choroidal lesions in Ihe left eye and had a visual acuity of
2(V40 «11 Ihu :i|^U and 2СУ20 on (lie left (O and Hi. A diagnosis
of mul Li focal choroiditis was made anrl started on oral slenjid^
after ensuring he Was negative for rapid plasma reaginr chest
X-ray; and other infectious causes. H;s svmptoms improved and
v itreous- ce3ls cleared cifver J weeks, hilt Ejy f> w eeki the number
of choroidal lesions increased in both eyes. Discontinuing ste­
roids and a diagnostic vitrectomy yielded a "reactive lymphoid
population of ceEls." He was started on inlravaious acyclovir
wilh a presumed diagnosis of hcrjieLk TetiniLis; the righl eye
lesions slabili/ed acid became pigmented poslvitjeclomiv: Ikjw-
ever, the left eve conLinued Lo progress wilh inner retinitis and
hemorrhages nesemEtling acule reUnal necrosis I агк! li. St’eing
con1iriLi«3 progression of Ihe left-eye lesk>n-s, arlifungal vfjri-
conazole was addled. Further progression of inner retinitis i.Kf
and hemorrhages prompted a vitrectomy and геИгъаГ biopsy of
the left eye, which was diagnostic ol primary ocular lymphoma.
Systemic evaluation for central nervous system involvement was
negai ve for 2.> ^ a rs , allcr which he developed a lesion in the
pons. H e received systemic chemotherapy, supplenwnlal intra­
ocular methotrexate, and is nogaLive lor cells in his cerebrospi­
nal fluid and eye ior the past 5 years. Both retinas noiv show
pi lamented Qunched-OUt scars sliriLilaling niuHifoca! choroidi­
tis iLI- His final visual acuity is 20/20 on the righl and 20/30-
on the left tbllowing cataract surgery and stabilization of the
lesions.

;Л-3-, f r u n i t j.i k:r ul , b l w j IJ i p e n : utsi nn .■

OTHER LYMPHOMAS AND I '£.33 A d u l t T-cell Ееuke m i a / l y m p h o m a {hum an
T-Eymphotrophtc v i r u s : HTLV),
RELATED CONDITIONS
A —L : T h is 3 9 -ye a r-fltM t a u c i^ a n wom an presented w ill:
gradual, painless jcfecrease in vision in her right eye over 2
monLhs, noL associated il It redness, pholophobia^ or pbo-
Adult Т-Cell Leukemia/Lymphoma Lopbias. She had received a slum bed I transplant 3 year>.
A d u l t гГ н : е 1 ] le u k e m ia / ly m p h o m a is a r e c e n t l y d e s c r i b e d previously f u r adult T-cell eukemia/lvmphoma and was pres­
en ll у in remission. She had had several infectious cxjiviplica­
c lin ic o p a th o lo g ic e n tity c h a ra c te rize d by an e x tre m e ly
tions ever lhe previous 3 years, including Fsvudnm onas and
a g g re ssive c o u rs e , a le u k e m ic o r l y m p h o m a t o u s p ro life ra ­
XlreptcK nccus baderem ia, cylomegalovLrus rwiclivaLion,
t i o n o f h y p e r l o b a t e d p e r i p h e r a l У ce lls, a n d a n a s s o c i a t i o n
А кегплы и'М отхъ'Н з sinusilis, m ucoculaneous ^ratl-vers-us-
w ith in fe c tio n by a re lro v iru s r h u m a n T - ly m p h o t to p ic host disease, bronchiolitis obliterans, and hypertension.
viru s typ e I Ilie s e p a lie n ts d e v e lo p in fil­ She was r e c e i v i n g Ceftin fur it recenL sinusitis and fever 1o
tra tio n o f m u ltip le organ syste m s, w h ic h m ay in c lu d e 102.8°F ( 3 9 . 3 ° t l ) , Com bivenl, prednisone 1 5 mgr azilbro-
a p a tte rn of in tra o c u la r in v o lv e m e n t s im ila r to th a l in mycin, and A d v a i i . V b u d l acuity was 20/70 right eye and
20/20 lefl eye w ilh a moderate afferenl papillary defect on
p a tie n ts w ith o c u la fc -C N E n o n -H o d g k in 's ly m p h o m a ' '
Ihe righl, 3/1 1 color plates on the righL, a n d 11/11 on Ihe
a n d a c u t e r e t in a l n e c r o s is ( E 'ig u ie ] 3 . 3 3 ) . 15J' 361 ih e latte r
lefl. The vikeous was lull of debris and membranes ■A.i and
pre se n ts w ith re tin a l a n d p e riv a s c u la r in filtra te s a ffe c tin g obscured some ol (he retinal changes that consisted ol a
b o t h a rte rie s a n d v e in s , r e s e m b li n g fr o s le d - b r a n c h a n g iitis , swollen oplk nerve i i nI iI Unites willun .:. rclinitb, ind
re tin a ] v a s c u litis , c y t o m e g a lo v ir u s re tin itis , a n d a c u te r e ti­ perivascular whitish :n fill rates with feathery borders resem­
nal n e c ro sis. H em orrh ages aroun d (h e in filtra te s are not bling fros led-bra neb angiitis [В and О . The left fundus was
a p r o m i n e n t fe a tu re , u n lik e c y t o m e g a lo v ir u s a n d h e rp e tic normal with no vitreous cells 113). An^iojjram revealed
breakdown ol lbe bJotid- rel trial barrier '.vi 111 diffuse leakage
re tin itis [Fig u re I 3 .3 3 B , C, G, and II). P o o r response lo
from (he vessels in the poslerior fundus апгI staining of the
a n tiv ira ls , o r a p a tie n t fr o m an e n d e m ic area f o r H T L V - l
oplic disc anti areas o f rel i nit is (E and F l She was started
v ir u s s u c h as J a p a n , S o u t h A m e r i c a , th e C a r ib b e a n is la n d s
on intravenous i^anc i с lew ir; aqueous sample returned nega­
and 1 're n c h W est In d ie s a n d tro p ic a l A fric a , s h o u ld a le rt tive lor cylom eyalovirus (C M V J, herpes sjmplex virus iHSV:.
th e c lin ic ia n to c o n s id e r H T L V - l r e t i n ilis j a d u l t T - c e l l l e u ­ and herpes zoster virus by polym erase cJiain reaction (PCHJ.
k e m i a / l y m p h o m a in t h e d ia g n o s is . Serum toxoplasma and rapid plasma rea^in w ere nega­
The viru s a ls o causes a m y e lo p a th y c a lle d Jl'l'L V - tive. M ultiple cerebrospinal fluid samples were negative for
^plignant c e i l s and in feel ion. Magnetic resonance im-iiging
a s & o c ia le d m y e lo p a th y . The p ro v im s HTL.V-1 in te g ra te s
of t h e brain and orbilb revealed no new pathqJogy. Afler no
ra n d o m ly in t h e g e n o m e o f t h e h o s t c e lt w i t h o u t a p r e f ­
response Lo systemic valgancrclovir and equrvocal response
e re n tia l in se rt io n s ite , lh e in le g ra lio n is m o n o c lo n a l in Lo bO mg prednisone lor 2 weeks each, a diagnostic vitrec­
a d u lt T -c e ll le u k e m ia / ly m p h o m a p a tie n ts and p o ly c lo n a l tomy was performed. Vitreous samples W e r e negative for
in th e l y m p h o i d ce lls o f t h e p e r i p h e r a l b l o o d o f p a tie n ts viral, lunga[r bacterial cultures, nega(ive PCR Ген parvo BIS^
w ilh l-n i.V -a s s o e ia le d m y e lo p a th y. M osl o c u la r ly m p h o ­ HSV-1 anil -2, varicella-zoslcr virus, CMVS human immuno­
m a s a r e o f Ь ч :е 1 ] o r i g i n . H I I V - 1 -in d u c e d in tra o c u la r ly m ­ deficiency vim.1;. H 6D and H7LU. FJCK for K T L V f and 2 was
not a v a ila b ly The vitreous cytology was read as: "m ixed
phom a is a rare cause o f T -c e tl Lym phom a: th e o th e rs
inflammatory rnfilLraEe, w ilh w eak CD3-positive and CD2D-
s p re a d to th e e y e fr o m m y c o s is fu n g o id e s , p e rip h e ra l T -c e ll
neg^tive lymphocytes* likely reactive and noL diagnostic of
l y m p h o m a , a n d S e n a r y s y n d r o m e (see C h a p t e r 1 4 ) .
a Jymphoid malignancy." FVjstvitrectomy the media cleared,
and I here was a hrnl ol reduction in the eslenl ol the peri­
vascular infiltrates (C ). The vision gradually decreased lo
20/100, Lind the pnlicnl left on a cross-country Irip on an
empiric Ireatmenl o f 1 mg of w eekly meLhoLrexale. She
relumed (j weeks laLer with further decrease in vision lo
count fingers at 1 loot (30 tm j and increase in the exlent of
lhe reJinal chiin^t1* ( H I . A refieal vitrectomy and a louch prep
ol a retinal biopsy revealed cells consislenl with T-cell leu­
kemia/lymphoma tl, fj . Flow cytology showed lar^e C D 3 — T
c e i l s that coes pressed C IJ4 and Cl>25. In lhe m eanw hile
Lhe left opli-c disc becam e swollen IК and she developed
small "snow balls" in the inferior viLreous. A n aggressive
themoLherapv reqimen with higb-iltise melhotrexale vin Lhe
С З т т а у а rtiservoir o v e r lbe nex1 3 monLhs resolved lhe oplic
disi inlillraLeb and she Ьаь remnined disease-1rtie in her lefl
eye (L) wiLh a visual acuity of 20/20 lor 2 + years. The rrghL-
eye vision remains nl light perception.
ьц&цтриа^) ti.ijj-'i.njf у ни 5 u iu 6 ij^ n Jrj J - т Й О
Richter Transformation i t . 3 4 R e ti n a l i I n v o l v e m e n t si m u Ea t i n g f u n d u s
J l a v i m a c u l a t u s in s y s l e m i c l a r g e - c e l I n o n - H o d g k i n ' s
I t c h i e r t r a n s f o r m a t i o n is d e v e l o p m e n t o f h i g h - g r a d e n o n - ly m p h o m a ^
llo d g k in ly m p h o m a or H o d g k in tym p h o m a in p a tie n ts
A-С: This heallhy 53-year-old W o m an noled гесел! blur­
w ilh c h ro n ic ly m p h o c y llc le u k e m ia o r s m a ll l y m p h o c y lic
ring of v i s i o n in Lhe right eye. Her visuaE acuity was 20/25
l y m p h o m a .B ila t e r a l v itre o u s c e lls In a p a lie n l w ith
in lhe righl eye .and 20Л in lhe loll eye. Amsler grid lesLing
Ea ig e 1 1 -c e l l ly m p h o m a re p re s e n tin g R ic h te r tra n s fo rm a ­ revealed (UraCemtra] 6о(йпта1з: in the righl lyflij In lhe ri fiht
t i o n h a v e a ls o b e e n o b s e r v e d .: 4 eyE* there w em 2 4 vilneous cells and the fundus showed a
rulicutar pa I Lorn of yd lo w ish cl urn ping of pigment si m a i l ­
ing Luncius flavitnaculatus al lhe level ot" lh e retinal pigmejil
A ng ioe ndot heJ ip matos is epithelium iK P ti thi^jughoul lhe macuta and jux Lapap i 11ar у
N T e o p l a s l i c a n g i o e n d o t h e l i c i m a l o s i s is a r a r e f o r m o f e x t r a - area (Ali. There w ere several areas ol uubreLinal w hite infiltra-
nodal la rg e c e ll ly m p h o m a c h a ra c te rize d by m u ltifo c a l tiqn h-uperonasally iBj. The I el I eye was поггл-аЗ. Early angio­
grams revealed lhe pigmenl clumps- lo be UypoПJ otescenI
p ro life ra tio n o f n e o p la s tic m o n o n u c l e a r ce lls w i l h i n th e
cm a background of greater than normal choroidal fluores­
lu m e n o f b l o o d v e s s e l s . ! t Is a r a r e , f a t a l d i s e a s e c h a r a c t e r ­
cence :Cl. ТЬете was lale slainjng in lhe area ot Lhe w hile
ize d b y w id e s p re a d In tn v a s c u la r p ro life ra tio n s o f m a lig ­
in fill rate. Angiograms of lhe lefl eye- were norm .a!. .Medical
n a n t ce lls o f p u t a t i v e e n d o t h e l i a l o r i g i n . C l i n i c a l l y , fe v e r evaluation far inflammatory and neopEastic disease was neg­
o f unknow n o rig in and d e r m a lo lo g ie a n d b iza rre n e u ro ­ ative. Her visual blurring gradually improved, and 7 weeks
lo g ic m a n if e s t a t io n s p r e d o m i n a t e . O c u l a r c h a n g e s in c lu d e Ia lei her visual acuilv was 20/20. She si ill noled slighl Ios? of
i r i d o c y c l i t i s , k e r a l i c p r e d p i La le s , v i t r i t i s , p a p i l l e d e m a , a n d light anti color sensiLdvily. Six monlhsi after Lhe onsel of visual
symptor^fc she no'ed axillary I ymphadertdpathy. Tumors were
re tin a l v a s c u la r a lte ra tio n s , in c lu d in g hem orrhages and
d is c o v e r s in lbe lefl supraclavicular area, reLroperiloneal
re tin a l a rle ry o c c l u s i o n . I n f i l t r a t i o n o f th e c h o ro id
area, and lefl breast. Biopsy revealed a histiocylic, non-
p ro d u c in g a c lin ic a l p ic tu re s im u la tin g H a r a d a 's d is e a s e Hodgkin's lympEioma (reticulum cell sarcomaj. She received
m a y o c c u r o c c a s io n a lly. E iis to lo g ic a lly , Lbere is p a n u v e a l systemic corticosteroid and anti metabolite therapy, and 14
in vo lv e m e n t w ilh g r a n u l o m a t o u s Irid o c y c litis in a d d i t i o n months afler the onsel of visual symptoms she was appar-
to v a s c u la r a n d s e c o n d a r y p i g m e n t a r y c h a n g e s r e s e m b lin g enlly In remi?-yio n . She has nol relurned for eye examination
s o m e w h a l h y p e r t e n s i v e c h o r o i d o p a l h y . rl h e v a s c u l a r e n d o ­ hut can read Lhe newspaper w ilh the right eye and is still
asymptomalic in the 3eft eye.
t h e lia l ce lls s h o w s ig n s o f m a l i g n a n t t r a n s f o r m a t i o n .
D— I: This apparently heallhy 67-year-o3d man developed
Mu nod vision in the letl eye in association w ilh a fundus
picture sfrrajlalind km [jus I lav imacu talus : [ J :. Angiograpliv i t
and F) was simitar to that in ( C i . Hiu visual acuily was 21У20.
M edical evatanilion was negative. Sis weeks taler his acuity
had declined to 2CVS0. There was an increase in the damage
Lo lbe К PE :(J-tj. Several л т о тЬ ь later he developed lymph-
adtmopalhy. Biopsy revealed ni large-cel! lymphoma.

R e t i n a l i n v o l v e m e n t in E y m p h o c y l i c l y m p h o m a .
|-L: Rapid visual loss occurred in EioLh eyes o f a 4ti-year-
old wom an caused by well-dit'fercnLialed Ivmphocytic lym ­
phoma. There was marked retinal perivascular and oplic
disc infillralion in both eyes. This infiltration cleared within
a month of cobalt irradiaLion IrealmenL. and visual acuity
improved from counting fingers lo 20/100 in both eves.
I A - I , I гD m Ц . и ь e l . i l . " . J - L . Ir u n i L tv w J ( A n d C l a r k '■ | r. I j ■I: i. i w it h
b f i r T n i ii lu n I'rLim I I f A m w i c i r t ltM Jma.1 о I C Jp h lh lH irtJlL t^ ]/.: r t p y t J g h t b y
Г Ii l- >!j fj hi Гh I rr i : l 1 Л л > 1 t j f c J i:- il К .'.Im j, 'r 'jn iu iz j- i. L m v r c n u i l . r [ l i e
U c L in .i' A.1I:is , S .n jn d u r s 2 0 1 II. 9 7 Й - 1 Щ ]2 [> - M I U -Ч. | j . 7 Lift
 ©
к .

m j
Л * ' ж w

' П ■
'■■Я1

Т(}Т г я ш гщ р ц п з s in jd $ y iiu d ^ |
Multiple Myeloma \ Hemorrhagic optic n e u r o p a t h y and visual loss
caused by multiple myeloma,
M u ltip le m y e lo m a is a n e o p l a s l i c d i s e a s e o f p l a s m a c e l l s
A - D : This 67-year-old wom an reported Murred Vision in
t h a t i n ils a d v a n c e d P l a g e s p r o d u c e s o s t e o p o r o s i s , p u n c b e d -
Lilt.1 lefL ?:ye of I WMik's duration. Visual acuity was 2W.30 in
oul bony le s io n s , m u ltip le fractu re s, and bone Lum ens.
lItl1 ri^hl eye лпс! counting finders al в fool 2.44 тсЧотч in lhe?
P r o p Loses c a u s e d b y b o n y i n v o l v e m e n t m a y b e l h e f i r s t s i g n
Feft eye. The riyhE fundus was normal. There were some cells
o f t h e d i s e a s e .372 K a r e l y, t h e o p l i c n e r v e m a y b e i n f i l t r a t e d in thy vilrenus ol" Ihe left eye. Nule coLLon-wool patches Hind
and cause a p ic tu re o f o p lic n e u ritis a n d , in s o m e cases, opacification Arrows, AJ of lhe optic nerve head posterior
c e n t r a l r e t i n a l a r t e i y o c d u s k r t i .J7i3 : O n e p a tie n t seen at Lo I by hHmDnhage£ Angiography showed minimal capillary
lia s c o m T a lm e r Ey e In s titu te w it h o p lic n erve in v o iv e m e n L dilation and sLaininy o f the o plic disc (B and Cl. The clinr-
cal impression was m yelom a infill rati on of the oplic nerve.
responded p ro m p tly to e xte rn a I-b e a m irra d ia tio n (I'ig u r e
She had a total dose o f 2000 rad of cobalL-ЬО lo [he poste­
1 3 . 3 5 ) . " C i l i a r y b o d y p l a s m a c y t o m a /1 ' c h o r o i d a l p la s m a -
rior pole over л 2-w eek period. Three monLhs fater her visual
q l o m a . . ' 1, a n d e v e n v i t r i L i s a n d r e t i n a l v a s c u l i t i s a s m a n i f e s ­ ao jjty wiis 2^/70 Lind the oplic disc was slightly pale ID 1
-.
ta tio n s o f m u ltip le m y e lo m a h ave been observed. * M ore
Metastasis o f systemic tumor lo the retina and optic
o fte n p a tie n ts w it h m u ltip le m y e lo m a and W a ld e n s tr o m 's
nerve.
m a c r o g l o b u l i n e m La p r e s e n t w i t h c lin ic a l fe a tu re s second­
E - L . A .>5-year-okl African A m erica n vvo riim sutferud л rapid
a ry l o h y p e r c o a g u la t io n . S e ro u s re tin a l d e t a c h m e n t s d u e l o
progressive visual change in the lefl eye! over i weeks. Her
Lb e ir o s m o t ic p ro p e rtie s o f a b s o r b in g flu id are s e e n , w h e n visual acuily was 20/20 in the rijjfit eye and 20/400 in I ho
h i g h - m o Ie c u ! a r - w e i g h l im m u n o g lo b u lin s e n te r th e sub- loft e y e .The n^hl fundus was normal. The lefl fundus showed
re tin a l space. T h e y c h a ra c te ris tic a lly do not le a k flu o re s ­ a w hile disc and full-lhicknoss necrosis of lhe surrounding
c e i n d y e s i n c e t h e o u t e r b l o o d - r e t i n a l b a r r i e r is n o t b r o k e n relink associated with hemorrhages and a serous detach men I
(see C h a p t e r 3 ) . A n e m i c r e t i n o p a t h y w t i l i d e e p i n k b l o t - l i k e
extending Co lhe m acula :E and F.'. The vessels on ihe disc
rind surrounding retina showt-чЗ focal endolhelial decom ­
r e t i n a l h e m o r r h a g e s o c c u r s w h e n t h e b o n e m a r r o w is i n f i l ­
pensation. aneurysm formation. and leakage it i And N . Her
t r a te d w i t h m y e l o m a cells (s e e C h a p t e r 6) .
serum я nlibodies lo Toxoplasma, herpes simplex virus-1
and -2, and varicella-zostor virus w ere wiLhin normal range.
Repeated 2-weekly intravitreal ganciclovir infections over b
Lymphomatoid Granulomatosis weeks did nol imprcjve Lhe retinal findings, ih e suffered a
seizure during Lius time, which led to a computed tomogra­
Ly m p h o m a to id g ra n u lo m a to s is is an a n g io c e n tric and
phy scan detection of a central nervous system lesion, hilar
a n g io d e s tru c tiv e ly m p h o p ru life ra tiv e d is o rd e r th at p re­
adenopathy, and a lung biopsy.. co n frrmaLory ft>r adenocar­
d o m in a n tly a ffe c ts lu n g s . lip s t e i n - H a r r viru s K N A can cinoma of Ihe lung. A d iAgnostic vitrectomy, retinal detacb-
be d e te c te d in m o s t cases. In a d v a n c e d cases, th e r e is a n ment repair and retinal biopsy w ilh silicone oil placement
o ve rla p w ilh la rg e В -ce ll t p n p h o m a .384 M o s t o p h Lb a lm ic H) revealed metastaLic adenocarcinom ij. Hem atoxylin and
m a n if e s t a t io n s o f t h e d is e a s e a re t h e re s u lt o f c ra n ia l n e rv e aosin and electron microscopv of the lunj] lesion i| and 1
showed larue malignant cells wiLh nuclear cyLoplasmic
in vo iv e m e n L. In L r a o c u I ar in v o lv e m e n t, h o w e v e r m a y m a n ­
ratio. Toluidine blue staining ol the retinal biopsy revealed
i f e s t as g r a n u l o m a t o u s p o s t e r i o r u v e i t i s / 1' ' o r f u n d u s p i c ­
tumor cells (Ki.
tu re S im u la Lin g a c u te p o s t e r io r m u l t if o c a l p ia c o id p i g m e n t
I L l o L . L .o i j r l v ^ ;, lit \?r. J m i A d L e b e r j } ,!
e p i t h e l i o p a L b y . 3a A ease w ith b ila te ra l e x u d a tiv e re tin a l
d e t a c h m e n t s t h a t r e s p o n d e d l o o ra l s te ro id s h as a ls o b e e n
r e p o r t e d . ' " 4''

Posttransplant Lymphoproliterative
Disorder
P o s llr a n s p la n t im m u n o s u p p r e s s i o n c a n b e a s s o c ia te d w i t h
Iv p s le in -B a rr v im s -in d u c e d l y m p h o p ro life ra tive d is o r­
d e r w h ic h m a y m a n i f e s t as i n t r a o c u l a r l y m p h o m a . "4
l > e m o l s el a l . 1 '" r e p o r t e d a S 9 -y e a r-o ld m an w ilh sin g le ­
lu n g tra n s p la n t who d e v e lo p e d a c h o rio re tin a l le sio n
tb a L was in itia lly s u s p e c le d to be c y to m e g a lo v iru s re ti­
n itis or to x o p la s m ic re lin o e h o ro id ilis . V itre o u s b io p s y
re ve a le d m o n o c lo n a l p ro life ra tio n of В ly m p h o c y te s .
Im m u n o g lo b u lin gene rearran gem en t and lip s le in -
lla rr viru s w ere d e te c te d by p o lym e ra s e c h a in re a c tio n ,
d e d u c tio n o f im m u n o s u p p re s s io n Eed l o re g re s s io n o f th e
E e s io n .^
 ffi

| | ?ивд )[' i i M j y .u j / pua s im i^ f d u d r f j^ f Q

METASTATIC CARCINOMA TO THE 13.36 Metastatic carcinoma lo the retina and vitreous.

RETINA A-ID: This 42-year-old wom an w h o had received treat­

ment lor metastatic breaM Lancinoma с о т р Ш ^ ф q f flaat-
M e ta s ta tic c a rc in o m a lo th e re tin a occurs in fre ­ епЕ- Examinalion revealed- cu a n c vitreous, opacities near
Lhe surface o f the reLina 'A and Si. Fluorescein angiography
q u e n t l y . " l0 ' Et u s t i a l l y o c c u r s I n o r » e y e b u l m a y a f f e c t
r e v e le d patchy waits От leaking relinal vesseJs fC and [J:.
b o th t ^ E s jQ3 lu ltln illy lh e re lin a l m e ta s ta s is m a y b e i n d is ­
Vrtreotf5 bitipsy revealed metastatic breast t a r t ] noma.
tin g u is h a b le f r o m a n is c h e m ic in fa rc t o f th e re tin a ( J ig u r e
E—1: This 49-year-o]d m a n o o m p l a ined erf dizziness, head­
1 3 . 3 6 A ) . A s l h e l u m o r e n l a r g e s , il p r o d u c e s a d e n s e r w h il- aches, dysarthria.. and *i$ht hem i p a r e s is. Examination
ёбЕт o p a c i f i c a t i o n o f ( h e r e t i n a i b a L m a y s i m u l a t e n e c r o t i z ­ revealed a solitary white retinal lesion Гп the left eye (E[.
in g re lin ilis c a u s e d b y to x o p la s m o s is , c y to m e g a lo v ir u s , o r Lom puled tomography and ппчэ^пе1гс геьопппсе ima^-
o t h e r in fe c tio n s (H g u re J 3 .3 6 L ) . O v e r l y i n g v i t r e o u s cells in$$ ul Ihe brain revealed m u l t i p l e rcodulaT lesions IF I. C h e s t
roLmL^enoLjTam revealed enlarged mediaslinal nodes a n d
m ay nr m ay n o t b e p r e s e n t ..v ' to lo g ic e x a m i n a ­
a n o d u l a r density in lbe right middle lube ( Q , F o s E m o r t e m
t i o n o f th e v it r e o u s in s u c h cases j n a y e s ta b lis h th e d i a g n o -
e x a m i n a t i o n of l h e e y e s r e v e a l e d a solitary melastalic ual
T h e b o r d e r s o f m e ta s ta tic le s io n s in th e re tin a
cell L ^ r d n o m a къгоп jn L h e r e L i n a :H a n d Г). Nol с Eh aE Ihe
are m o r e I r r e g u l a r t h a n in c h o r o i d a l m e ta s ta s is . In a p p r o x ­ t h o r o id (arrow, H is unaffected.
i m a t e l y o n e - h a l f o f r e p o r t e d cases* c h o r o i d a l i n v o l v e m e n t
IA —I, Г г и т L c y i d nl -1, s "■1 9 9 0 , A m c r i m n M e d i c a l A s s u l m LIu t i . A l l ri^ h d
was a ls o p re se n t. M u ltip le p e riv a s c u la r w h ite in filtra te s ГЬЗСГЛйА I
m a y a c c o m p a n y t h e m a i n t u m o r m a s s .'kL'
■ - - ■«
 C u ta n e o u s m e la n o m a m ay o c c a s io n a lly m e ta s ta s ize 11.37 Metastatic cutaneous melanoma to the retina
to th e eye, and in a p p ro x im a te ly 20 ^ b o f such eases il and vi(reousb
d o e s s o lo th e re tin a ra th e r t h a n to th e u ve a l t r a d (fig u re
A ,md IJ: A 4.'i-year-о Id worn аг noLed Hollers in lhe lefl
1 5 l(kl- JL'-' [ n som e c a s e s it m ay m e ta s ta s ize lo иуе. Three years previously she had a LuLaneous melanoma
Lhe v itr e o u s a n d cause (h e p a tie n t lo c o m p la in o f v itre ­ esc i lied. £1оЬл1[ tfefilmenl was £jiven becalififi o f a posi­
ous flo a te rs th a t are t h e re s u lt o f b l o w n , c e llu la r, s p h e r i­ tive Eymph ro d e bEopsy. VisuaE acuity was 20/20. 51iL-lamp
cal d u m p s o f m e la n o m a ce lls s u s p e n d e d in th e v itre o u s ^JmmiiftatitHi ot the -ofl eye rev^aj.ed ljo Iden-Eirxswn spber-
uleb зп :he anLerior vitrE*ouu cavil у Ai and pigmented c e ik
c a v ity ( i’ ig u re 1 3 .3 7 A ). T h e s e cell d u m p s are s u ffic ie n tly
^martalin^ from lhe region of lbe oplic disc. i'Bi. Angiography
c h a ra c te ris tic and d iffe re n t fr o m lh e irre g u la r c lu m p s of
revealed some slainin^ of Lbe oplic disc. The palient died 4
p ro life ra tin g К Г Е : c e lls (to b a c c o d u st) lh a l th e d ia g n o s is
mofitbs laler jn Kpile Ы anti metabolite iherapv.
o f m e ta s la tic m e la n o m a s h o u ld b e su s p e c te d . Ч Ъ е v ilre - С and D : Relina.! meUslasis in a 44-yeai-old man 3 years
ous in filtra tio n m a y be a c c o m p a n ie d b y su p e rfic ia l grav- afl-ет excision of я culaneous melanoma.
b ro w ti in filtra te s arranged in a d e n d ritic p a tte rn w ilh IA j n c H. Io n ; B a b tr tto u i:l .hi.' ; ( .tncl LJ, (л и л Lfchdfi .: i ■
■I U.Lviclurf.'1' '
fe a th e ry ed g es in filtr a tin g lh e n e rv e fib e r la ye r o f th e re tin a ■U I '0o2.. Л п п сп L.hn M e d i l ,il Ая;оы.ь1щ п. ЛИ ri|^hls reserved. t and I j Ih j ,
Yhnnujt^i. L .ivvrentL1 lh e K fliu .il AlLib, Siu rid ir-, ?G 1 0. rH7iMJ-7(12l'l-
s u rro u n d in g th e o p t ic n e rv e h e a d ( F ig u r e ] 3 ..3 7 IJ J . l .a ig e ,
jW20-9. p.2 75 .j
h e ig e -c o lo n e d p l a q u e s o r d u s t e r s o f t h e l u m o r ce lls i n t h e
v itre o u s m a y p a rtly o b sc u re th e fu n d u s fr o m vie w , hi o th e r
cases th e re m ay be lo c a lize d irre g u la r p !a q u e s o f m e la ­
nom a ce lls w i l h i n th e re tin a (E 'ig u r e ] 3 .3 7 С and D ). In
s p ile o f s u b c o n ju n c tiv a l in je c tio n a cid s y s t e m i c t r e a t m e n t
w i t h a n ti m e ta b o lite s , th e t u m o r i n th e eye m a y p r o life r a te in b l o o d flo w (tu rb u le n t flo w in t h e c h o r o i d v e rs u s l a m i ­
a n d c a u s e r u b e o s i s a n d s e c o n d a r y g l a u c o m a . 1' " n a r f l o w i n th e r e t in a ], a b s e n c e o f fe n e s tr a tio n s in th e re ti­
T h e re a s o n s f o r t h e ra rity o f m e ta s ta tic c a n c e r t o ( h e ret­ nal v a s c u la r e n d o t h e l i u m , and i n h i b i t o r y fa c to r? p re s e n t
in a c o m p a r e d to th e u v e a l t r a d are u n c e r ta in . D iffe r e n c e s in th e v itr e o u s are p o s s ib ly I m p o r t a n t / 11
PARANEOPLASTIC RETINOPATHY 1 3 , 3 Cance r-associated ret inopat hy,

ASSOCIATED WITH CARCINOMA A: Cancei-associated rot i перл Lhy in an elderly пплп w h o

noled Lhe rapid progression o f loss of pc?riрЬг?гл1 vision «and
{CANCER-ASSOCIATED nyctalopia. Note the narrowed retinal vessels and aEtsence of
RETINOPATHY OR CAR evidence of retinal pigment epithelial changes other Chan Ihe
juxtapapLEIary atrophy that was presenL in both eyes.
SYNDROME) В and С: A 72-year-old-woman developed total achrom a­
topsia, bilateral cenlraE scotomas, predom ina nL suppression
lh e ra p id d e v e lo p m e n t o f visu a l lo ss a s s o c ia te d w ith ot" сопи response; by eleclroieLinoj’ram, and narrOW in^bf the
b i/a rre v is u a l s e n s a tio n s , n y c ta lo p ia , rin g s p |a m a t fla t relinal arteries. She died 9 months JaLer from metastatic car­
e le c tro re ttn o g ra p h k response, p ro g re s s ive re tin a l a rte ria l cinoma. Histopathologic exa mi nation to w n led loss of pbo-
n a rro w in g , and no o r m in im a l changes in th e 3?L3E a n d tOrBcEplora mosl marked in lhe m acular aneat :E3 and О and
selective loss of cones elsewhere.
o p t i c d i s c m a y o c c u r as a r e m o t e e f f e c t o f a s y s t e m i c c a r c i ­
n o m a , m o s t f r e q u e n t l y a s m a ll c e ll c a r c i n o m a o f t h e l u n g Acute Vogt-Koyanagi-Harada-like syndrome in a
(l i g u r e Т З . ^ В А ] ^ 1' J ' ' Л f e w v i t r e o u s ce lls w e r e n o t e d in patient with melaslatic cutaneous melanoma.
one c a s e ," and aqueous ce lls i n a n o t h e r . ’ 1'' K l u o r e s c e i n D - l: This 7 ] -year-old wom an had had a melanoma of the
a n g io g ra p h y in tw o cases s h o w e d e vid e n c e of m o ttle d doisum of" Iter fool removed 3- years- previously. Two week*
before admission she had noled headache, progressive Vit­
h y p e r flu o r e s c e n c e in b o t h e y e s .43' A b lin d n e s s m a y o c c u r
iligo of 1bn- skin of Lhe face and arms fD and E), deafness,
w ith in 4 m o n th s . I"h e v i s u a l s y m p t o m s m a y a n te d a te th e
floaters, and progressive lost of vision in bolh eyes. Her
d is c o v e ry o f th e c a r c in o m a , h is t o p a t h o lo g ic e x a m in a t io n
visual acuity was light perception w ith poor projection in
s h o w s severe d e g e n e ra tio n and lo ss o f th e r e c e p t o r ce lls bolli eyes, ih e h id 1 +- aqueous cells and ftare and keratic
a n d . u n lik e re tin itis p ig m e n to s a , m i n i m a l d a m a g e to th e precipitates, i - vilreous cells, and lat^e areas of depigmen-
K PL and norm al c h o r i o c a p i l E a r i s 4 1 2 '4 ^ - 4 1 7 ^ 1-4 ^ In one LaLion of" IHie? t horoid and posterior fundus IF- and C ). Her
case th e r e w a s lo ss o f g a n g l i o n c e l l s ." 11 ' E l e c t r o n m ic ro s ­ general physical examination revealed inguinal Eymphade-
nopalhy bill no other evidence of m elaslalic disease. The
c o p y in one p a tie n t re ve a le d i m m a t u r e m e la n in g ra n u le s
nodes were posilive Гог melanoma. Computed tomography
w i l h m e la n o ly s o s o m e s , su g g e s tin g a b n o r m a I m e la n in s y n ­
ot" the brain and abdomen was negative, and elettrorel bio­
t h e s i s a n d re 5o r p L i o n . J " T h is su g g e s te d to th e a u th o r s (h a t graphic responses w ere eKtinj’uished in bttfn eves. Lumbar
in c re a s e d m e la n in s yn th e s is and m e la n in c o n te n t w ith in pLinclune revealed f3 0 lymphocytes and spinal fluid protein
Lh e f t P t in r e s p o n s e l o a h o r m o n e ! L k e s u b s ta n c e p r o d u c e d ot" У0 mg/dl. Irealm ent w ilh systemic corticosteroids resulted
b y th e c a n c e r m a y c o m p r o m is e its a b i l i t y l o p h a g o c y t o & e in rapid return of visual '•unci ion lo 10/50 in the fight eye
a n d m a in ta in n o r m a l tu rn o v e r o f re c e p to r o u te r se g m e n ts. and 20/70 in lh e left eye. Ten monlhs after Lhe onset of visual
symptoms, ihe vitreous inalammalion was minimal anti lbere
J h i s in t u r n m a y c a u s e p h o t o r e c e p t o r c e ll d e g e n e r a t i o n .
were scallered ftjeal areas of depigmentation o f lhe choroid
in both eyes (H and Jl. The patient led an active Life and was
able Lo read unLii Lhe time of her death, caused by metastaLic
melanoma E5 monLhs later.
IB , n n J t . Гr u i n C . u ^ n l’ L ; i I . L J - I . Г г о т C i .ib s .1 -1-1 .
 Cogan el nil. re p o rte d a u n iq u e case o f p a ra n e o p la s ­ i J.39 Mela noma - a s s o c i a t e d retinopathy.
tic r e t i n o p a t h y s i m u l a t i n g а соле d y s tro p h y in a p a tie n t
А t)4-year-old man presented w ilh pbotopsi-a, difficulty w ilh
w ilh recu m e rit b l i n d n e s s o n e x p o s u r e l o b r i g h t l i g h t r to ta l night Visibly and reduced peripheral visual Field in boLh eyes
a c h ro m a to p s ia , b ila te ra l c e n tra l sc o to m a ^ n a rro w in g of Гог 3 months. He had been recently diagnosed with malig­
t h e re tin a l a rte rie s, a n d d e c re a s e d e le c t r o r e t i n o g r a m t ^ E l C ) nant melanoma of lhe maxillary sinus. The corrected visual
a m p litu d e s a ffe c tin g p re d o m in a n tly cone fu n c tio n .'1-1 acuity was 2Q/2U in bulh eves. K w u lls ol the anterior seg­
M e d ic a l e v a lu a tio n d is c lo s e d a p e lv ic p le o m o rp h ic car­ ment anti fundus examination were normal in boll: eyes. An
eleclroreflino^ram showed marked reduction in lhe b-wave
c in o m a o f presu m ed u te rin e o rig in . 5 h e d ie d because o f
amplilLfde under scotopic testing conditions to a bright flash.
m e ta s la iic d ise a se 9 m o n t h s a fte r o c u la r s y m p t o m s d e v e l ­
Tndirecl im m unofluorescence w as performed on cryusec-
oped. H is to p a th o lo g ic e xa m in a tio n o f eyes re ve a le d lo s t
Licins of unfixed human retina usin^ serum and lg<_l Iram the
o f l h e re tin a l re c e p to rs a n d p r o m in e n t a tr o p h ic a n d p ro E if- patient. Fluorescein isolhmcYanate-labr'Ied anLihuman Igti
e ra liv e c h a n g e s in th e p ig m e n t e p ith e liu m th a l w ere m o s l and jgM were used as secondary antjbodiet. A w eak bul
m a r k e d in th e m a c u la r a reas ( F ig u r e I 3 .3 8 IJ a n d C ) . specific linlieling of bipolar cells was observed Inrrowl. The
K e ltn e r a n d a s s o c i a t e s 11, fo u n d a n tib o d ie s to norm al visual tlaLus Remained slable for ih-u nchxt 12 months, when
he died from metastatic disease.
fre s h re tin a in lh e seru m of one p a !te n t w ith th e C A ti
_
syn dro m e and p o s tu la te d an a u to im m u n e m e c h a n is m ll-rnrnSn[jhct .il. rill
' svirhpurn^skxi.1
fo r re tin a l d e g e n e r a tio n , Ih u rk ill el a l. id e n tifie d seru m
a n tib o d ie s to a sp e c ific a n tig e n {C A R a n tig e n ) w ith a
m o le c u la r w e ig h I o f 2 3 k D a in th es e p a tie n ts .’ " ' ' fh e y
p o s tu la te d th a l th e d e m o n s tra tio n o f h y p e rs e n s itivity to
fu lly e x p la in e d o n th e b a sis o f e ith e r th e c h o r o id a l in fil­
sp e c ific a n tig e n s in C N b tis s u e is c h a r a c t e r i s t i c o f para-
tra te t h a t ty p ic a lly sp a re s t h e c h o r io c a p illa r is , o r e x u d a tiv e
n e o p la s ia a n d is a p o t e n t i a l l y u s e f u l i n d i c a t i o n o f o c c u ll
re tin a l d e t a c h m e n t (se e C h a p t e r 3 ) . 'I h e p a th o g e n e s is o f
n e o p la s ia . P a r a n e o p la s tic d is o r d e r s h a v e b e e n id e n tifie d in
t h e r e c e p t o r c e ll d y s f u n c t i o n is p r o b a b l y s i m i l a r t o t h a t i n
a s s o c ia tio n w i t h d iffe re n t typ es o f n e o p la s ia : m e la n o m a ,
o th e r c a ic in o т а - a s s o c ia te d re tin o p a th ie s .
c e rvic a l, c o l o n , p ro s ta te , a n d b re a st cancer, 'lh e m o s t c o m ­
m o n a s s o c i a t e d c a n c e r is s m a l l - c e l l c a r c i n o m a o f l h e l u n g .
The re lin a l s p e c ific im m u n o lo g ic re a c tio n s , s u g g e s tive MELANOMA-ASSOCIATED
o f a u lo im m u n ily , m a n ife s tin g as h ig h -tite re d a n tib o d y
RETINOPATHY (MAR SYNDROME)
re a c tio n s w i t h th e 2 3 -k l> a re tin a l G A R a n tig e n , are now
known to b e lo c a t e d w i t h i n t h e r e t in a ! r e c e p t o r s .'1' Ac u te p a ra n e o p la s tic n ig h t b lin d n e s s m ay occur occa­
I h u r k i l l e t a l. h y p o t h e s i z e th a t a c a r c i n o m a - r e t i n a im m u ­ s io n a lly in p a tie n ts w ith m e ta s ta tic c u ta n e o u s m e la ­
n o l o g i c c to s s -r e a c t i o n is r e s p o n s i b l e fo r th e i n d u c t i o n o f n o m a . ' 1 " 11, 'ih is m ay be a s s o c ia te d w ith a c u te a n te rio r
th e u n iq u e a n tib o d y re sp o n se e n c o u n te re d in p a tie n ts and p o s te rio r u ve itis, p a tc h y d e p ig m e n ta lio n o f th e c h o ­
w i l h C A R , w it h v i s i o n l o s s d e v e l o p i n g a s a c a n c e r - e v o k e d ro id , v itilig o , d y s a c o u s is . and severe v is u a l Loss [E 'ig u r e
a u l o i m m u tie r e t i n o p a t h y .152a T j S ( . 3 8 D - I J l * 3J 1134,431 '['h is syn dro m e occurred in one
There is s o m e e v i d e n c e t h a l t h e v i s u a l d e f i c i t in s o m e p a tie n t re c e ivin g b a c illu s C a lm e tte -G u e rin tre a tm e n t fo r
o f th es e p a tie n ts m ay show im p ro v e m e n t fo llo w in g cor­ c u ta n e o u s m e l a n o m a . ' 1^ ' lh e v is u a l s ym p to m s are asso­
tic o s te ro id and c h ^ id ^ Era p y .'ll-1flL<i,'45e'4JS,'<29 In g e n e ra l, c ia te d w i t h an ER fc ! t h a t m a y s im u la te th at o c c u r r in g iti
h o w e v e r , t h e v i s u a l p r o g n o s i s is p o o r . I s ' e u n o l o g i c d i s e a s e - p a tie n ts w ith c o n g e n ita l s ta tio n a ry n ig h t b lin d n e s s ’ or
i n c l u d i n g o p t i c n e u r o p a t h y , o c c u r r in g as a r e m o t e e ffe c t o f t h a t m a y b e e x t i n g u i s h e d . ' 1'1 5 - '1"
am eer [e .g ., c e r e b e lla r d e g e n e r a t i o n , b ra in s te m encepha­ It is p r o b a b l e Lhat th e acute c h a n g e s in th e eye, s k in ,
litis . m o to r n euron d e g e n e ra tio n , p e rip h e ra l n e u ro p a th y, a n d e a r are an u n u s u a l i m m u n o lo g i c re s p o n s e t o t h e m e l ­
p o ly m y o s itis , a n d m y a s th e n ia ), has b e e n k n o w n fo r m a n y a n o m a . a lth o u g h ih is c o u ld n o l h e v e r ifie d in Lh e p a tie n t
y e a r s , b u t i t s p a t h o g e n e s i s is l i k e w i s e u n c e r t a i n . ' 1^ 1 seen al Bascom P a lm e r Ey e In s titu te (H g u re I 3 .3 8 D - I ) .
P a tie n ts w i t h b ila te ra l d iffu s e u ve a l m e la n o c y lic p r o lif­ Sera o f p a tie n ts w it h M A R m a y d e m o n s t r a t e h ig h lite rs o f
e r a t i o n a s s o c ia te d w i t h o c c u lt c a r c i n o m a m a y a ls o d e v e lo p im m u n o g lo b u lin s re a c tiv e t o re tin a l b i p o l a r c e lls (E 'ig u r e
severe lo ss of re tin a l re c e p to r fu n c tio n th a t cannot be Ш з э у * - 4#
 P a tie n ts w ith M AR. u n lik e ih o s e w ith C A R , e xp e rie n c e 1 3 .4 П P a ra n e o p E a s tk v ite llifo rm d ys tro p h y-
p r i m a r i l y c e n lr a l v i s u a l lo s s r a th e F t h a n r i n g s c o t o m a s a n d .,
A—D: This i i a 58-year-old white male w h o com plained of
e a rly, th e ir E R G does nol show lh e se ve re ly d e p re s s e d o r worsening vision ir both Eyes and n ulited a Kef images w ilh
a b s e n t a -w a v e in d ic a tiv e o f p h o t o r e c e p t o r d y s fu n c t io n ." '' lights and television screen and photopsias and a (Mangle of
V itilig o has b e e n re p o rte d in a s s o c ia tio n w ilh c u ta n e o u s blur on [he left side. H e had lef[ axillary node resected for
m e l a n o m a s i n a s m a n y as 2 £№Ь о Г cases, in a fe w p a tie n ts a malignant № n m ^ N o Qriflftary cutaneous lesion was
it m a y b e a c c o m p a n i e d b y i n t r a o c u l a r i n f l a m m a t i o n .'^3,442 found. H e was treated w ilh iiUeriuron nilpba 2 В , w inch wan
completed a month prior. H is visual acuity was 20/20 in Lhe
O t h e r d ise a se s lin k in g v itilig o and in tra o c u la r in fla m m a ­
i iц.ЬI eye and 20/25 in Lhe lefl eye.
tio n , p a rtic u la rly c h o rio re tin itis and p a tc h y d e p ig m e n ­
Itiu u rC i^ sy с>Г LJr. Lttur I . k jcrlL j s .i
ta tio n o f th e fu n d u s , in c lu d e s y m p a t h e t i c u v e i L i s ' ’ IJ a n d
v iiilig in o u s c h o rio re tin itis (b ird s h o t c h o r i o r e l i n i t i s ) . 4L|J
J h e fr e q u e r n a s s o c ia tio n o f n y c t a lo p ia in v i i i l i g i n o u s c h o
r i o re tin itis , its o c c a s i o n a l occurrence in a s s o c ia tio n w ith
s y m p a t h e t i c u v e i t i s , a n d ils o c c u r r e n c e in t h e p a t i e n t i l l u s ­
t r a t e d i n f i g u r e 7 . 3 9 i n d i c a L e t h a t t h e r e c e p t o r c e l l s as w e l l
as t h e m e l a n o c y t e s m a y b e l h e t a r g e t o f t h e i m m u n o l o g i c
re a c tio n .
m e la n o m a . 11'1 A u lo a n tib o d ie s a g a in s t a 12 0 -k E)a p h o to ­
re c e p to r p r o te in , b e -s lro p h in , a n d b i p o l a r ce lls h a v e b e e n
Paraneoplastic Vite]lifortn Retinopathy is o la te d . EiRC ] and e le c tro -o c u lo g ra m re su lts have been
A c u te -o n s e t b ila te ra l m u ltifo c a l RHL d e ta c h m e n ts lh a l v a r i a b l e .'1'34" 1" c' I t is q u i t e Eik e ly th a t p re v io u s ly re p o rte d
re s e m b le v it e llifo r m re tin o p a th y have been re c e n tly rec­ c a s e s o f m u l l i p l e R E TEi d e t a c h m e n t s i n p a l i e n t s w i t h s k i n o r
o g n i z e d { f'ig u r e 1 3 .4 0 ) . S o l o d e h a n d a sso c ia te s r e p o r t e d 3 uveal m e la n o m a fa ll w i l h i n th e s p e c tru m o f p a ra n e o p la s ­
cases* 1 w ith c h o ro id a l m e la n o m a and 2 w ith c u ta n e o u s tic v i t e l l t f o r m r e t i n o p a t h y . I ; i '
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1 61 McCormick\\r. Harama' JM.BetteTF:\lscua.1 a^alo-n alonsн Ц вта*Т с(d e h'an.v*m
skc al referee t tese -хд.гт i g ir №e ssien j Ijcsa. J №ипки[| 1968 232^11-&1
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162. fi'Dis'm &1. C5. Л^1ре.ч BL Tebng eciasK and csoencnis ачзгдй cl Ihe Lfinslen
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161 Ssoar \VH Frrra’y гезр^йтс ■! te afli; ne^e a t lb sresl^ ci f^I ialu'e: a t t j'e r
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161 Vftil ne- Jr EE Mggmn аИвиапршпар! ihsfipicdHi.tV^ 0:rtan-c t65:53:ll&-7
161 teffp atttJl Sect Ш. S d ra E Л Ej[al. GCW g_ene muidai n la'ifcEsegisgiltng
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1 69. Efrocnif, Inevin Г.-'F. Zaicer R.el a.Tw г ж я ё n famJsn refnaстыпав hemarabm^
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ca lecK ата 12 new aaes LJarrarcen/ 1 Мй:1 Й.' 62-72.
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CfhlldnHM ££7:63215-20. '
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arg arm 5? ncsum. B1 J C-phnaJro^ 1S7'-;E6 ^33-43.
l S I CramaLy JL. ^1» D OaJa Eicns inlie H.-e ubxr L+±i na^u syitf a-*. 3r J ^mslniai
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200 Sfiks»'g VF. JR «п Н ^еЧ гсаj а м а а r-iilaaalh^apc f.rtdrgs h a ireasc aid 11
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202 -a mx Ш . fcn x h =-. Rasrsac' aiciacrai:l’\ ■ , wn hnsl-Un±L dжа:е. Аг^
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203 Metmai KL. Иваг Щ Lnaj's ditase. нем?.1 : cl ts i!5fihire aici ас^- cl ala-^эkrered.
AmJ fftd 1964:21695417.
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211 9id?y У. G'eef:J. ^лйп 1 Fielra а^спайж: 1xociilar nan-ieslalicfls al wi Hip-pfJ-
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212 Sdiitdaf ^F Sarin:J. MacCtDrao Ff: Иеггэтс*а-й5 clШзcp! с азе. Ca^ J iJlhslma
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213 itfinid D. hejurn -FH.topbdie ittrae VerandHumi te v. -e m —Lncau-Svifir-ifl’.
rcflid!rCpitJhcll95-:64 67-9.
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213. IskifaEl;! 1! Уйсз h, ]a\\ [. ei ji. CaalaT Ьетипд cnt cl Ihe cclc dac. J Сn hejo-
ftMidnd m4:1S9-6Z
216 ten ra К G'aiudai ES E!ar P.F. i al Сстйа! с i -jf ер пезеппе Lse aid n a ila aaeit 11
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217 'iim^na I'J. lep law Ни ,^1ж п 5. el а. Ei jla i кге aala^1eoY^^ rana
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222 a lf F. щ ii. Sfii'm J el Я. леШга! сп 'Лte va' H f0 4 i caL dieaae b,ma iiip a « a r
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223 iiale C. Glenn G. bar 6. et al l ipiwed delflclta' cl -н^ге iMaicire in he mca -iDpel-
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22^ 3f^h Al'. Алтае Щ Sh elds CL. e! si. -Sdcav 'el na cifi la> hEflFar>jo^iK. -a^ t cena;
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223 ja l Kiixr L.гвткпеп I. Stmrnign R : sjfl!era relr al arg cmate leicr a n maahr
хс^гЛп' J^hlhilmDl lSa&' 03 333-1
226. Ft.Fa;leii*i4 DM JL МатадетаШ a! nacja pJchersaHXflltfd'.vff
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227 AalzTl.. TrJkmEcI! G. Faslart*'g Щ el ^1aa.la xc'jer a>drecmil a^cflia.
ftMidmfc £цд Ш7;18и77-1
223 'Jkas жл Etl. AxfflCfl LS. Ha-l С FEHnatopenajc 'e! na eeraci venl n axtanla:is
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229 nei Flf.№вша WLF: НсЛ rtf. IncfflBft remrgiditiilcma cl lhe cclc dsK. An J ODfUiajra
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200 .eita g М. Заепаг Ш WtyttF Ire pienl leiix?Й m -iapel-jnJau daa;s. Ar-di
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203 Ш Х R6.™ rtpael-Ljh-dai daaM:lhf rBcacnnaiond E'^in'enld йЛуапоитйзэЕ
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тсазарс.ап-d irmuxfaaicaaechaailef^licfl.Cfhlliam'Dia^11933:9С:Ё46-55.
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зропатик regTeiiia1 cl areinsl ax^'a.finna 1995^:263-9.
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bfie:oed n tne sl'rcraJ cels al ratal щ а на Aiei CpMhiJHOl l Ё5Э " 7£2э-3й
241. Kadn WtL HopaJfls 0. Lmeran Ш, et a. Fuinsis of Te wmHррйЧгса j ijtlm
apJKifi'prcfen. J Lteir Мй 199Й241535-9.
'Ш. Acp e DJ. Sc at-erg \f tyhnifc GJ. А р г la a ПбЛтгет of ™ Hfipel-ijndau relriL
angiomas, I. НкйнРикщ d trrafe] кэгсв. Arcli Ufrtti£no 1974^2:126-30.
2i3. Sited and feeds nesse phdmrajdafomrfighfll
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24. Arate \R Smlh TR С г^гтщ cf anjaitalGiii relire. Ath ^iham d 1969 31*93-9'
24. 3C Dwfteraw far neunl ag стэгаж а ргьэм^ла щ с ижг ton Cprlhamo<
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247. ЧС ИеИ&& 1A GoiilaTine JE. bagrciii aidmragtFHil cf wr hpaeHnflai.
dKaifi. in: Pi^trai GA .tys e II, Sadai Dl. ecras. тимси ar dmas, Менп'аи Afp elsr-
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LtmpEJloiE j! raittei^idaTQHTHi. CffilhilmcSu'g 1SS220-7-EC.
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'd l 'isssclc-n. SpfilldntiDCtf 195Э;9С:£40-7.
202. Alwara N- te\ na №, ’’j Ьрткнкпа treaJed ififli «rtaolin diatatoHit: Кнар AnJ
С^тшпит 2002:134:7110-90.
203. Sifrnkt-ERrti LT" Юканш С, бакеГгЭ LA, d.iJ. Deceita end otmciicalcni af
pTCUi/Tifflic lhaipyol pspferv capital^ т е п ™ : "as. ОЯЧЬэНчеду SDOfiltK 1255-E6
254. Sd'irkr С. чаи E te j ian^HR (E&te i! aa 1 luealiftarLfa:relnalmgflmatoasii
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200. Sacfrfctt R. fccgBly ft ^acer FK e; ai. tenqpcnn ййтЛгапс Ihaift- of йс ejb и m
rtfrti сарнгу lffifflaT9ana.fldafl|3tiltialmd 2C;&Se354-43.
20(5. [ 4hrS£ Clsc^H, ladfguei C-Dter^n" ^л.Ш ’эг/иаЫ .-щ ^а' a'dtnelaltwff
laclar itefjpy wlh кдакп t fcr aijarae rai Hppe 4ndaj G iC K cl Ife isna Fiffra
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207. WAnglNT, Jirg KJ.Harn'e K.sld.inlrj^Kl ,а,|Ьл;таЫ1:е'а?у^,J|(:a
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208. liting Щ ^r.ew EK Dcutar wn hpaehUnlzL diease:chta UDdals ard aremra ueanHita
Cun {tel ^pMltiinul 2C08i'92l3-7.
209. Dstdse: 0-. Walsh =B, H ^s GJ. Рзр(1кй"£ *Й 1 ( и н т п а d Г^рспаиjs.to'Cd
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203. Dsn Л .й й в в JfRR Mcfar JN Bktuea ретарй™ snnsl ha^jndtis j caserepqt
Ach {>*lhama l £66 7S:77-&^.
201. [а л ш й зт ЭД. Оогшу Eft Hansnoanalhe т к е : cdHe nehtL A.'cf' CpKtoli:!
196enO&14QJ-ia
202. De Lie'. JJ, ~.ertz S Fuler. L. Bel га зщ^ота aid |№ i 0 :e^- iKian reflntiscli 2a. CpKfriInc
Paedturflatt199^13:7m
203. Gcll) еэ f. Fammalro JU, SMttml TF. el a, Falral sag ипашв mass a■smairal en']f ra ia
dfiacrire'f: sjgar. Reliia 19Ы -152-7.
20i. Uedodc RC. 5h e и Eh eks CL el si. И й cal hEnang ч-^ъ\l e j j E t n h a /s i^d11i n us
pgrmtoa. R«ni Ifflfel №274-7.
200. FslM; С Saita J. 3ianahan J.Argicn^DK reli is t c и к й й a me nilafe de Stsrgank A
р-эи d'un cas cii^e. J Fr OcfJafic11983;12.Й&Г^S2.
200. Etfatfal A?. Uaikwitz Jft. Gursf jfl. el a. О м а (пс msritesteteiscf laitema Am
Ш а л ю "9Э9;107:697-7ш.
207. Krtiid MC, jfs n 'ftft.C c ja ' n d a trsl Гг jitiin pt n е А г т о . Зсги OjCtnair:!
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203. Ь е о ^ Ш .й к а т й О в Я Е г а ^ .А п а ^ в в ^ З Б а и й щ ^ ^ г о о й n W H iw tln
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209. Giver CF. Eitacflal A?, t o S e! :± ju-jem с гкпзрошгг: iBbdonstii5helmed luids legore
агл hmattbgc мгзтсяена эгйас^агВ.С^ПГЕПйЦ' 19с!9:Э£:В£[|Ч.
270. E t^ ii j. l m i \1 ЕИИлЙГТhe pt\u en:e j r a t i dsease In Lfnoric |рш ^1с
leiiaEna EiielJintt' 2053:17:27-39
271. nj e i НАц ^Iraaami BH. {>cu ar kwatranenl г leuhemk aia alec d senderi ■Vch ftf-lhaiiM
t961;6&49a-50ft
272. Oil er^W. fiindus dianges r l&Ja^s Tran: “jn ( № m 1ЭБ1 ;4&:445-71
273. QifeCH, ImesCfi.BJiodiX.flrtBriflrsegrHd sdiav<a caalfalcnind isenpien n
аник eJ^na.Arn D^hhami! 1979^11:173944.
27*. De Ju n1 ,Gikt \VR. Ffce ТА. er al. Cf lie dac ns^iaiaJsrйайзл associ^d *Й1 aalir
hraloififlin aculii^inpxt^c tifte™ . Retina 1982ifi1-4
270. [tee JU. 41ftШ ‘С1 ^genai EL Fjeira mkicaleuivsnii h !e(.ksmt:. 3r J Scftfainia
I Se&&2 303-74.
27C. Hct JM, GffdcrrSmh EC. Hefeial аЬшгпййв г cbease al Ihe Nod. Br J Cthl^n-a
13C&&3145—60.
277. OifdH^hlheopllctijndLBin ietriaena ая! с1сду. ccqnul с ire
[ШКЕЙс гс+э. Й^а ODCina ira-1964:42:201 -10.
273. Ркекта! ffl, Ec&en aR, W :xr JF: el a. LsJ^iiclrtriranent cl ne Dpi с y.№. j Pecalr
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279. Sralz № J^UTiirn ffi. Atл laienic irii Ir i m cf me v treej: ri agxsc-d j f mis j a t
aGafsfrM.AinJO^Tairc 19й3^[у:32&-13.
j ij . Щ Hrfubon Df'. Ccirci.: r it ulcr as lhe pecenlrg maiteslanui cl a ils monastic
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231. Mstj R li;ltdm s 33c ran 1ейа1сп: cl eu^jeti a. J PBdatr 197^' 90:15S-7
252. Katih M Gc cn'ai EJ. H. er il. А(ящ нИй 'Зрипатп с aalation cf ffllienlb I'.ilh acje
ni'fl ckj letjfcenia сс^эпзт cf ocular ard тетгайх^: lindnp J ClinCnccl 1959:7:1ES-32.
233. 0>Kh. К Tstmas iiVG. FTkteIic ru rta ra tf cmnakric nan teilal en; t, dhkhnd
l^tjeKia.B' J Cphlftalir>D("l £fr27£j001 -E.
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Neoplastic Diseases o f the Choroid
A V a rie ty o f t u m o r s , in c lu d in g h a m a r to m a s a n d n e o p la s tic F4.01 Mac u la г d eta с h me n I can sed by ch о го ida I
tu m o rs o f lh e c h o r o id , m a y le a d to s e ro u s a n d le ss o f t e n melanocylic nevi.
to h ^ o t r h a g i c d e ta c h m e n L o f th e m a c u la . E x a m p le s u s e d
A —C : Serous delath m cn l ftf lhe macula t a used by a pig­
Ш ih L& te x t are p r e s e n t e d to Illu s tr a t e h o w Lh e s e c h o r o i d a l mented choroidal tumor ргеяитсч! to be a frfertii in a
L u m o r s m a y cause a c lin ic a l p ic tu r e th a t c a n be c o n fu s e d 27-ycar-old vydmari whej w jh seen in June1 1472 with a
w i t h d e g e n e r a t iv e o r j n f f c p a r t p f o r y d is e a s e s o f t h e c h o r o i d 2-week history o f blurred vision ]n the righL eye. l-ier visual
a n d r e l i n k a IT e c tin g t h e m a c u l a r a r e a . acuity in the ri^hc eye was 20/25. She had a two-disc: diam ­
eter, slightly elevated, pigmented choroidal lumor [AJl
O verlying Ihe lumor there was a dumbbell-shaped serous
CHOROIDAL NEVI detachment of the retina I вптлча) that extended into the
fovea I area. Angiography demonstrated a foe.я I leak of lluo-
C h o ro id a l nevi are d e v e lo p m e n ta l tu m o rs com posed o f
rescem dye into the subretinal space farrow, Hi. The fatal
b e n i g n m e l a n o c y t e s .1 l h e s e t u m o r s a r e u s u a l l y u o L e v i d e n t leak was Healed with sis 50-mm ap plications o i ihu argon
at b i r t h . Ih e ir m a x im u m p e rio d o f g ro w th occu rs b e fo re laser. The serous detachment resolved. H e r visual acu ­
p u b e r ty .-' H o w e v e r , u p t o 6 .5 ^ -i o f t h e a d u l t w h i t e popu­ ity roLurned It) 20/15 . Fen v-l-.ii - laler :b i;.n:;ii -pp'-.ii-
l a t i o n m a y h a v e c h o r o i d a l n e v i .1 s A l t h o u g h m ost do not unch^n^ed IС I. Visual acuitv is 2tl;20.
D - F S e r o u s d e t a c h m e n t o f th e m a c u la s e c o n d a r y to a c h o ­
a c h ie v e a s ize g re a te r t h a n o n e d is c d ia m e te r , s o m e reach
ro id a l nevus w ilh o v e rly in g d ru se n in a 6 7 - y e a r - o l d w om an
a lh a l m a y sim u la te th at o f д m e d iu m -s ize o r even
w ith visu a l fltu ily of 2CV23. There are Severn I sm a ll e le v a -
l a r g e m a l i g n a n t m e l a n o m a . I t is e s t i m a t e d t h a t t h e r i s k o f
liu n s o f th e teflrtal p ig m e n t e p ith e liu m ! R lab d y f i r l y i r g s m a l l
m a l i g n a n t t r a n s f o r m a t i o n o f a c h o r o i d a l n e v u s '1 is a b o u t 1 c h o ro id a l B E O v a s tu lir lu fts and b lo o d -s ta in e d e xu d a te
in 1 0 0 0 0 .'' O v e r a p e r io d o f m a n y years th e s e p ig m e n t e d ta rru w , I? '. Ea rly a n g io g ra m s d e m o n strate d several c h o ro i­

o r n o n p ig m e n te d c h o ro id a l n evi m a y cause d e g e n e ra tiv e dal n e o v a s tu la r Lufts ( a r r o w s , El. La te r a n g io g ra m s show ed

s la in in g or Ih u d r u s e n a n d ( E m r o id a l n e o v a s c u l a r m e m b r a n e s
c h a n g e s in B r u c h 's m e m b r a n e , d r u s e n d e p o s i t i o n [E 'ig u ie s
t C N V M s i o n th e s u r f a c e o f th e l u m o r < f).
14 0 1D and I 4 .0 2 ) , s e ro u s d e t a c h m e n t o f th e re tin a l p ig ­
G - r This 37-year-old wom an had s-ubnormal vision in the
m e n t e p i t h e l i u m ( K P l i ) a n d re tin a (I'ig u r e 1 4 .0 1 A ) , c h o r o i ­
r i ^ t eve for al leas! 14 years. Note the gray-white plaque
d a l n e o v a s c u l a r i z a t i o n [E: ig u r e 1 4 . 0 I D , C , a n d J } r c ir r in a l e
of filjrovastular tissue Iving on Ihe surface of pigmented
re tin o p a th y (I'ig u r e i 4 .0 1 Jl. h e m o rrh a g ic d e ta c h m e n t of choroidal tLimor lhal '.illrasonographically was elevated
th e m a c u la [ i l g u r e 1 4 . 0 1 (}.. v i t r e o u s h e m o r r h a g e , a n d EiP H 3.5mm St;1. Angiograms showed a t'N V.Vl (arrows, H and
h y p e r p l a s i a ( E ' i g u r e 1 4 . 0 j 5 . \ - C ) . J I" 1 ' C l u m p s o r p a t c h e s o f a funnel -shaped area of depigmentaLion (aftow,, I of lhe KPfc
o r a n g e p ig m e n t m a y o v e rlie c h o r o id a l n e v i. a lth o u g h th e y lEiat extends inferiorly from the lumor to the ora serrata. The
lumor remained unchanged during 13 years of follow-up.
are m o r e f r e q u e n t l y o b s e r v e d in g r e a te r n u m b e r s o v e r l y i n g
! —L: Hem orrhagic detach menL of Ihe m atu la taused by a
c h o r o id a l m e la n o m a s . Z o n e s o f a tr o p h y o f th e R P H a n d a
LN 'V M larrows, К Lind L' overlying lhe inferior surface ol" an
bone c o rp u s c u la r p a tte rn o f p ig m e n t m ig ra tio n in to th e
elevated pigmented nevus that has remained unchanged in
re tin a m a y o c c u r at th e in fe r io r m a r g in o f th e s e n e v i, p a r ­ size during 12 yitia rs o f fol I ow-u p .
tic u la rly th o s e th a t are e le v a te d a n d g re a te r th a n t w o d is c
d ia m e te rs in s ize (I'ig u r e Ы .0 1 С - ] and 1 4 . 0 4 J - ' - 1 . } . J ^ - l:
llie s e areas are caused by p ro lo n g e d d e t a c h m e n t o f th e fig u re 1 4 .1 6 ) and c h o ro id a l o ste o m a s and in p a tie n ts
re tin a th a t p re v io u s ly e xiste d in th at area, p r o b a b ly d u r ­ w ith c h ro n ic id io p a th ic c e n tra l s e ro u s c h o rio re tin o p a th y
in g th e g ro w th p h a s e o f th e t u m o r in c h i l d h o o d . S im ila r (see K ig u re 3 .0 S ) and tra u m a tic c h o rio re tin o p a th y (se e
zo n e s occur in fe rio r to c h o ro id a l h e m a n g io m a s (se e H g u r e S .0 2 H ) .
 W hen not a s s o c ia te d ^ vith a lte ra tio n s in th e o v e rly in g F4 .02 H isto p a t h o to g y ol ch o ro i d al n evi ca u sin g
R PE, c h o ro id a l nevi appear h y p o flu o re sc e n t th ro u g h ­ d is cifo rm m a c u la r d e ta c h m e n t,
out th e co u rse o f a n g io g ra p h y w h e n th e y o c c u p y e ith e r
A Hind B: M u Hi pie drusen, some of w hich are calcified, over­
th e in n e r p o n to n o r th e e n (ire th ic k n e s s o f th e c h o r o id . k ill^ a localized spindle cell nevus of lbe choroid lA'i and a
A n g io g ra p h y is h e lp fu l in d e te c tin g any a b n o rm a lity flat exudative detach mertl c f lhe nUinal pigmenl epi Ihelium
i n v o l v i n g c h a n g e in th e d e g re e o f p i g m e n t a t i o n o r p e r m e ­ iK F'li associated i 111 ntnv \ esse Is gndfefng from lh e choroid
a b ility o f th e R P E o v e rly in g nevi ( E 'ig u r e 1 4 .0 1 ) . Drusen inlo lhe ниЬ-KKt sp<Lce Ia now, В . The overKflhtf relink was
normal. 11н detochmenl was лп jjiifa c l.
o v e rly in g c h o ro id a l n e v i u s u a lly s h o w flu o re sc e n c e d u r in g
Disciform sLiЬ т л с u I л г liEjrovasculaf scar nnd proliferation
t h e first m i n u t e o f t h e a n g i o g r a m a n d e v i d e n c e o f s t a i n i n g
[jt lhe K l'L overlying л choroidal nevut. 1Ын scaf presumably
but little o r n o c h a n g e in t h e i;iz e o f t h e a re a o f f l u o r e s ­
resulted from hefnordiajfe of п-l^w - vessels rhaL had grown
cence d u rin g t h e l a t e r s ta g e s o f t h e s t u d y . A n g i o g r a p h y is Lhrou^h breaks in E3rnL : h membrane overlvinjj a choroidal
a ls o o f v a lu e in d e le c tin g th e p re s e n c e o f c h o r o id a l neo­ nevus. These ch arges led tc a mlsdfjagnosii of m ali^narl
v a s c u la riza tio n (Fig u re 1 4 .0 1 1 . EL and L ) . № K " IH i :i n e melanoma and enuc lea Lion of Che eye.
d e ta ils o f th es e c a p illa ry m em bra ne s m ay be p a rtly or :. \ -£., IrcniTr tl.it,:-.' 1tj-L: АГи^1V.'innu iyii, (jwrcinct i.. 1he Ни ;i i .l I Al 1.Ы,
li ,iu jv k ’ ri U N O , : j. 7 1 ft.?
c o m p le t e ly o b s c u r e d b e c a u s e o f th e re la tive o p a c ity o f th e
e xu d a te or re a c tive fib ro u s m e ta p la s ia o f th e RPE over­
ly in g th e m e m b r a n e : w h e n c a u s in g s u b r e tin a l e x u d a tio n ..
neovascuEar m em b ranes u s u a lly s ta in in te n s e ly d u rin g
t h e c o u r s e o f a n g i o g r a p h y . A n g i o g r a p h y is a l s o h e l p f u l i n H is to lo g ic a lEy r c h o r o id a l nevi are com posed o f any

d e te c tin g z o n e s o f КЕМ : a t r o p h y s u r r o u n d i n g th e s e t u m o r s o n e o f s e v e r a l b e n i g n c e l l t y p e s : s p i n d l e ce lEs, f u s i f o r m o r

[t-'ig u re i 4 . 0 1 E) . J h e e x trin s ic e ffe c ts o f t h e n e v u s o n th e r o u n d c e lls, a n d b ra n c h e d m e la n o c y te s . ]Ъ е у m a y be p ig -

s u rro u n d in g re tin a and RPE can be re a d ily assessed by m enLed or n o n p ig m e n te d . They m ay p a rtly re p la c e th e

o p tic a ] c o h e re n c e t o m o g r a p h y ( О С Г ) a n d fu n d u s a u to flu ­ c h o rio c a p iH a ris a n d cause d ru s e n a n d c h o ro id a l n e o v a s c u ­

o r e s c e n c e [ F i g t i r e I 4 . 0 5 ] . 1" l a r i z a t i o n [E 'ig u r e 1 4 .0 2 ) .
ChrtrtriJdJ ЛЛггр I i S3
 P a tie n ts w ith m a c u la r d e ta c h m e n ts caused by s m a ll E4. D 3 L o n g - l e r m t o Il o w - u p o f p r e s u m e d

p ig m e n te d c h o ro id a l le s io n s , a n d th o s e w ith larg er m a r e h y p o p ig m e n te d m e la n o c y lic c h o ro id a l n evi o r

e le va le d le s io n s of u n c e rta in g ro w th p o te n Lia l, s h o u ld tu m o rs o f fo w g ro w th p o te n tia l.

be observed c a re fu lly w i l h s e ria l p h o t o g r a p h s and u ltra ­ A -С: In Novem ber 1969 this- 60-year-old wom an presented
so no graphy to e xc lu d e th e p o s s ib ility of a m a lig n a n t wiLh visual loss caused !iy serous macular deLachmenL ever-
m e la n o m a . I f t h e l e s i o n is a n e v u s , p a r t i c u l a r l y Ёп a lying л SLibmacLil-ar elevated hypopigmented choroidal
te e n a g e r or young p a tie n t, th e d e tach m e n I m a y re s o lve Lumor (arrowheads, AJ. The cenler of Lhe lesion was hvper-
s p o n t a n e o u s l y . I n s o m e cases, h o w e v e r , w i t h p e rs is te n c e o f pigmented. The diagnosis was melanoma of the choroid.
Tfte pjatienl elected Lo have no Irealment. In M arch 19B5
t b e d e t a c h m e n t , la s e r t r e a t m e n t m a y b e n e c e s s a ry ( N g u r e
tfie lesion was Utichanged in diamelDi. Exctpl for a small
I4 .Q IA -C ) . T h e presence o f m u llip le drusen o n th e s u r­
amoLinl of liprd exLidnite in lhe center ol" Iho macula, most of
fa c e o f a p ig m e n te d c h o ro id a l Lum or, dependent /ones lhe SLibnetinal ovadale had resolved i H i . Note Lhal I ho super-
o f p ig m e n t e p ith e lia l a tt b p h y a d ja c e n t to th e tu m o r , and ficFal prgmented porLiun of Lhe tumor was Гагдег. In Octolner
o v e r l y i n g c h o r o i d a l n e o v a s c u l a r i z a t i o n is h i g h l y s u g g e s t i v e 1992 the lumor was unchanged in size (С, w id e -аnj’ It1view I.
t h a t t h e t u m o r is a c f t o r o i d a l n e v u s . W h i l e s e r o u s r e t i n a l Tlvere was ha s-LEhrc^li па I ox Lrda LLon. U in proEjafjle that the
d e t a c h m e n t m . a y o c c u r o v e r l y i n g a n e v u s , i t is m o r e o f l e n a pigmented portion of lh e tumor represents reaclive retinal
pigment epithelium :K;PEi hyperplasia overlying a chofbtdal
s ig n о Г g r o w t h p o t e n t ia l, p a r tic u la r ly i f a s s o c ia te d w i t h flu ­
nevu-ь.
o r e s c e i n a n g i o g r a p h i c e v i d e n c e o f i n u It j p i e p i n p o i n t a r e a s
□ and t: In 19Й.1 this b5-yenr-old w o m a n л tilled a posiltve
o f le a k a g e . (S e e s u b s e c tio n on m e la n o m a f o r d is c u s s io n cenlral s^fiLoma associated wiLfi an elevaLed non pigm ented
o f sig n s s u g g e s tin g g r o w t h p o te n tia l o f s m a ll m e la n o c y lic choroidal tum or in I he rijjhl inferior m a cu la r area (arrows.
tu m o r s .) S in c e s o m e c h o ro id a l nevi a n d m e la n o c y Lom as [].. N o le lhe bJood vessels wiLhin lhe lum or. An g iograp hy
(o n e o f th e c y to lo g ic v a ria n ts o f c h o ro id a l n e v i) m a y c o n ­ revealed e vid e n c e of RTEi d epigm entalion and cl Limping as
t i n u e to g r o w beyond a d o le s c e n c e d e m o n s tr a b le g r o w th , w e ll as staining w ilh in a n d on the surface of the tum or fE^.
H er visLial acuity w as 2 0 / 4 0 . L'JtrasoLind revealed a 3.2-mm
p a r t i c u l a r l y i n c h i l d r e n o r y o u n g a d u l t s , is n o l a n u n e q u i v ­
elevaled ch o ro id al medium-neilecl.ive tLimor. .M edical e v a lu ­
o c a l sig n o f m a lig n a n c y . 1 I t is i m p o r t a n t t o d i f f e r e n ­
ation revealed n o e v id e n c e o f m etastatic carcin o m a . The
tia te a n in c re a s e i n s iz e o f a n e v u s c a u s e d b y a n e x p a n d i n g LLimor rem ained unchanged dLiiinji 10 years-' follow-up. H e r
re a c tiv e p i g m e n t e p ith e lia l p r o l i f e r a t i v e a n d f i b r o u s m e t a ­ visual acuiLy al tast exam ination w as 20/2 5 .
p la s tic d is c ifo r m p ro c e s s o n th e s u rfa c e o f th e n e v u s fr o m F-L: In D ecem ber I L)6fi a small e le v a t'd w hile choroidal
g r o w t h o f t h e m e l a n o c y tic t u m o r i t s e l f [ E ' i g u r e s ] 4 .0 3 Л -С ! kimor i.F) was discovered during a routine eye examination
in this 46-year-<jld man. M e d ical evaluation ol evidence of
a n d I 4 . U 6 ) . l s ' Jfi
meLastati-с £:arcinoma was negalive. O ve r lhe subsequenl
25 years of follow-up Ihe lesion gradually enlarged and the
palienl remained nsymptomalic: Augunl 1 713 :Cjl, jLine 14715
IHi, M arch 19B2 OJ, anti sleioo angiograms If anti Kj. and
M arch 1994 (L>. Because ol the superficial resemblance to
a choroidal osluoma, Lillrasoiiographic examinations were
done on Itiree occasions l>elween 1977 and 1994. They,
along with orbiLal roenlgeno^ranTS. revealed no eviden-ce of
calcification.
 P a tie n ts p re s e n tin g w ith c h o ro id a l n e o v a s c u la riza tio n F 4 .( 1 4 T u m o r b r e a k t h r o u g h B r u c h 's m e m b r a n e a n d

s h o u ld be m anaged u s in g th e s a m e g u id e lin e s fo r tre at­ m in im a l g ro w th o f p re s u m e d m e la n o c y tic c h o ro id a f

m ent of n e o v a s c u la ri/ Jlio n a s s o c ia te d W ith presum ed n e v i fo EEo w En g p h o t o c o a g u l a l io n t r e a lm e n t f o r s e ro u s

m a c u la r d e t a c h m e n t
o c u la r h is to p la s m o s is and a g e -re la te d m a c u la r d e g e n e ra ­
t i o n . ] ^ L 7 r J 7 ,2 S T h o s e p r e s e n t i n g w i l h s e r o u s r e t i n a l d e t a c h ­ A-£: In Novem ber 1972 this 54-ycw-oId wom an presenlud
m e n t w it h o u t e vid e n c e o f n e o v a s c u la riza tio n a n d w t lh no w ilh melamorpFropsi a associated w ilh serous nil inn I detach­
c le a r s ig n s o f a g r o w t h p o t e n t ia l c a n b e f o l l o w e d f o r u p Lo ment surrounding а slightly elevaled pigmented choroidal
4 m o n t h s a fte r o n s e t o f s y m p t o m s , fo r e vid e n c e o f s p o n ­
tumor (arrowheads, AE. The diagnosis was melanocytic: cFk>
roidal tumor uncertain growth potential. W h e n :he rBtlhal
ta n e o u s re s o lu tio n o f th e d e tach m e n ! o r g ro w th o f th e
detachmenl felled I о resolve, racal laser IreaLmen! to л site
tu m o r . Ef n o g r o w th o ccu rs a fte r lh a l p e r io d a n d th e area
of fluorescein leakage on lhe lumor surface was done. The
o f flu o re s c e in le a k a g e is o u t s i d e th e c e n te r o f th e fo v e a , deLachmenl resolved Ej u ! recurred again in M arch 1973. The
th e a u t h o r r e c o m m e n d s p h o to c o a g u la t io n lo th e area o f tumor was unchanged ol her w ist1. Ar^on laser IrealmoroL was
Leakage o n ly , w h ile c o n t i n u i n g to m o n i t o r th e p a tie n t fo r dune iB i anti the deLachmenl resolved. She was follow ed
e vid e n c e o f tu m o r g ro w th ( I’ ig u re г 4 . 0 1 Л —C j . W hereas a I yearly intervals with ло change until .May 1979. Al lhal
som e of th e s e p a tie n ts w ill show e vid e n c e of tu m o r
time evidence ol a smaEI nodularity o f the lum or surface
wan noted (arrow. Cl. By Septumber 1579 a 2-ram nodule
b re a kth ro u g h B r u c h 's m e m brane at. th e site o f p h o to ­
of tumor exlending through Hruch's mWnbrane was evidenl
c o a g u la tio n , u s u a lly m any m o n th s or several years a fte r
I.mow, Djt. M edical evaluation for m elaslalic disease was
t r e a t m e n t , t h e r e is n o e v i d e n c e t o s u g g e s t t h a t t h i s a f f e c t s
nef^itivu except for chronic lympFiaLic leukemia that had
th e lik e lih o o d o f e x t r a o c u l a r s p r e a d o f t h e t u m o r ( F ;i g u r e been diagnosed several year* previous IV- She eEecterl lo
1 4 .0 4 ) . 2’ T h e d e v e lo p m e n t of a lo c a lize d n o d u le of have no Lreatmenl lor choroidal lumor. t.>vor lhe subsequenl
tu m o r b re a kth ro u g h on th e s u rfa c e o f th es e t u m o r s a fte r 6 years o f follow-up there was only slight enlargement of
t r e a t m e n t , p a r t i c u l a r l y i f it o c c u r s m a n y m o n th s a fte r th e
tEie choroidal lumor varnKwheads. E) as w e ]I an the overlying
Lumor nodule I arrow, Ё).
tre a tm e n t, m ay not n e c e s s a rily in d ic a te a change in th e
F-L: O n a rouline eye examination in April l?J3.1r a five
t u m o r 's g ro w th p o te n tia l {Fig u re 1 4 .0 4 ) . En som e cases
disc diameter elevated pigmented choroidal tLimor was dis­
th is e x t e n s i o n appears to occur m o re as m e c h a n ic a l d is ­ covered lerafioral to lh e left macula :l-l. A gray fibrovaocu­
p la c e m e n t o f p lia b le tissu e , ra th e r t h a n g ro w th o f tu m o r, lar plaque (arrow. F-l wa*. presenl on ils sl)rl3L& There was
th ro u g h a fo c u s of la s e r-d a m a g e d B r u c h 's m em brane. a JLono of atrophy, hyperplasia, anti inlraretinal migration of
O t h e r t r e a t m e n t o p t i o n s i n c l u d e p h o t o d y n a m i c t h e r a p y , 1" K P t extending from lhe tumor infenolempoTally almosl lo
tra n s p u p illa iy t h e r m o t h e r a p y ,a n d in tra v itre a l a n tiv a s c u -
the equator. Angiography demonstrated evid en ce ol choroi­
dal neovascularizalion w ilhin lh e gray plaque on Ihe tumor
fa r e n d o t h e l ia l g r o w t h fa c to r a g en ts.
surface. This finding and lhe /one of depend cmI retinal pig­
ment epithelial change suggested lhal Ihe lumor was a large
nevus. She was followed al h-raomh intervals wilhout any
change until March 1935, w hen she returned because of
metamorphopsia in Ihe Jofl eye. At lhal time there was e v i­
dence o f reactivation and nasal oxiensiun of d>e new ves­
sels I arrows, C ) on Ihe tumor surface. Nole Lhe iipid exudate
near the cenLer ol the macula. The area of Lhe new vessels
wan treated with argon laser '.arrows, Hi. By (_>c1ober 3986.
the exudate was gone (I) and (he patients acuity was 20/20.
N o further change occurred unlil M ay 1991 w hen tw o nod­
ules (arrows, 11 were noled on lhe lumor surface w ithin
i v area "■ previous laser t realm cmI. [Fiese two ic : l ■ of
lumor, which appeared to exlend ihrough B r u c h i mem-
Firane, enlarged slowEy over Lhe subsequenl year iarrows,
K.) although no definite change occurred in Lhe size of Ihe
lumor otherwise. Al LhaL lim e sFie had recenlly undergone
surgery and chemotherapy for ovarian carcinom a Unit had
extended Lo regional lymph nodes. In M ay 1392 she expe­
rienced a vilreous hemorrhage in the left eye. This cleared
and, in OcLoEier 1993, lhe choroidal Lumor and Ihe foci of
extension of 1итот Ihrough Bruch's membrane showed m ini­
mal evidence o f enlargement (black arrows, Lj. The presence
of p i^ n en l debris in the vilreous overlying the tunvor I white
arrow, L: suggested lhal meal necrosis w ithin lhe Lumor nod­
ules m ay have been responsible for Lhe vitreous Fiemorrhage.
The funduu remained unchanged w hen she was last exam­
ined in Decem ber 1994.
1 4 .0 5 E x trin s ic e ffe c ts o f lh e n e v u s .

A: Ll'fects ал [he surrounding niLina I t lin f l pigment epithe­

lium can fie readily assessed by optical coherence tomogra­
phy and fundus autoffuoreseence. Fundus photograph w ilh
orange piymenl and subretiinaJ fluid .
On iu fid Lis a uto fluorescence, о г л п ^ pigment appears as
fotjnI hyperaulofluonoscenL spoL. Гп add Иion there it diffusa
dispersion of otgnge piemen! within lhe ^Kl- iптрлrLinfj, dif­
fuse hyperauloffoufesence lo thu $RF.
C: P ^ M imed dispersed llpolusdn (orange pi^menLJ is seen in
Ihe suIsrel inaI space.
iFrtrtii SJfitfh tr ,il..1' wilh prtnribtEfin.j

1 4 . f J b O p i i с d i s c m e t a n o c y l a m д.

A: A 50-year-old white man noted to have o plic disc tumor

on a routine examination. Patient had no symploms and his
v isual acuity y^as 20/20. Nole a m elanocvtic 1umoi that is
intrinsic to the optic nerve head with fine vilneous pij^rmml
dispersion.

Optic disc me Ian (icy tos is

8 acid C: A .35-year-old woniian seen for a routine eyt! exam i­
nation was found lo have pigmental ion (.if lbe oplic disc sur­
face. H e r visual fields were normal, ruling oul compression.
D -G : This 55-year-old African Am erican diabelic male
reported "a w ave com ing towards the center of my vision"
far J weeks;. His visual acuity was 20/20 ал Ihe rijjht and
20/25 on lhe left. 3-1is ri^ht fundus was normal. The lefl
fundus had a darkly piymenled mass on lhe oplic disc lhat
extended inlo lh e adjacent temporaJ retina. Two pockels
ol subrettnaE fluid, one extending to the Eaveal center and
lhe other I о the inferior equatorial region i arrow L associ-
aled with lipid, and a vascular lesion were seen emanalin^
from the lesion. Fluorescein an^io^ram showed a lacy net­
work o f vessels early that leaked late in the angiogram. Laser
pholocoayulation of the choroidal neovascular membrane
resolved jbe subneLinaJ fluid and symptoms !Hj.
H-K: Ih is .ith-year-oJd Indian w om an presented with sud­
den loss of visFon in her right eye to counl finders. A darkly
pigmented mass covered most ol her rij^hI oplic disc., w iih
some extension into the nerve fiber Eayer. The m acula
showed opacification secondary to occlusion of the tempo­
ral branches of the central retinal artery (1). An angiogram
confirmed poor perlusion of lhe superior and interior branch
arteries supplying [he macula Ij and ft).

I Q - G - j C a U r i e s y ud L j r . K u t f u i E i t i j t : H - K . . и :.и г 1 с у н м? D f . V l l h i l i L j u f i r .i
.i ■11 U r. A 111■>lI ■!.. u|]Li .1
MELANOCVTOMA F 4 .0 7 D iffu s e sclero c h o r o i d a l m e la n o c y tic n e vu s/
schw annom a,

M e la n o c y lo m a [Fig u re 1 4 .0 6 A ) and m a g n o c e llu la r n e v u s

A—E: Tin i 5 9-year-old boy w ith subnormal vision ir the left
are h is to p a th o lo g ic n im e s used to d e s c rib e h ig h ly p ig ­ eye had diffuse thickening and hyperpigmenlAlien of Lhe
m e n te d uveal nevi th a t are com posed o f 1 л rg e , ro u nd, Lempural and inferior fundus, 3 shallow retinal detachmt1пI
p o ly g o n a l, o r fu s ifo rm m e la n o c y te s w ilh s m a ll n u c le i a n d interiorly, and blurring of the optic disc margin in lhe left
o c c a s io n a lly a b u n d a n t n u c l e o l i . 'I'h e s e s a m e c e lls a r e t h e eye (H5). Note lh e ^bsencifi ot choroidal т а rkiподы in the lefl
eve 'L3l com pa rad Wilh iiiu normal Tight eye i A I. Ihe left eve
p re d o m in a n t c e ll t y p e fo u n d in eyes w ilh d iffu s e uveal
was enucleated. Histopathologic exa m iration revealed dif­
m e l a n o c y l o s i s .1 O c c a s i o n a l l y m e la n o c y to s is o f th e o p lic
fuse Ibickenjng of the choroid and sclera, w hich were infil-
d is c w i t h o u t t u m e fa c tio n c a n b e been ( F ig u r e 1 4 .0 6 1 i a n d
Lraled with benign spindle m elanocy tic cells in lhe m acula
C]J. C l i n i c a l d i f f e r e n t i a t i o n o f u v e a l m e la n o c y to m a s fr o m and inferior fundus (IbW-pp-wer, L , and higher-pDwuis, D and
o th e r h ig h ly p ig m e n te d nevi com posed o f s p in d le and E|\ Note the posterior bow ing of Ihe thickened choroid and
d e n d ritic m e la n o c y te s is not p o ss ib le , except when th e sclera in Ihe macu Lit region Ia nows, С and D).
t u m o r i n v o l v e s t h e o p l i c n e r v e h e a d . f t e n i g n m e l a n o c y tic E-J: A 14-year-old girl presented in tanuary 1У35 Ejucnuse
of a recenl change in the vision in lhe right eve, which had
tu m o r s th a l are in trin s ic lo th e o p tic n e rve h e a d a n d m a y
always been am blyopic. The fundus appeared almost identi­
e x te n d In to lh e s u r r o u n d in g c h o r o i d a n d n e rv e fib e r la y e r
cal lo lhe left eye o f the palienl in K. In addition lo the thick­
o f th e re lin a , h is to lo g ic a lly are in v a r ia b ly m e l a n o c y L o m a s .
ened and darkened choroid posteriorly and interiorly I here
Fe a tu re s, o lh e r th a n th e ir in te n s e b la c k o r g re e n is h -b la c k was a JocalijLtid serous relinal delachmenL and a gray sub-
p ig m e n ta tio n , th a t to som e d e g re e d iffe re n tia te m e la n o ­ relinal neovascu lar complex lairow, R in Ihe mat ular area.
c y to m a s f r o m o th e r u v e a l n e v i in c lu d e a n a p p a r e n t g re a te r There w ere some inflSmp'rna^ry cell*- in lhe vi I ret j u s . lhere
p r o p e n s i t y to e x h i b i t s o m e lo ca l g r o w t h p o te n tia l b e y o n d was blurring of the o plic disc margins. The left fundus was
normal. Angiography revealed a choroidal neovascular
p u b e r ty ; a g re a te r p r e d ile c tio n fo r u n d e rg o in g sp o n ta n e ­
membrane (arrow, G ], a large zone of depigmenlation o f Ihe
ous n e c ro sis; a g re a te r lik e lih o o d of In v o lv in g a d ja c e n t
le lira l pigmenl epilhclium extending temporally lo Ihe m ac­
s t r u c t u r e s , i n c l u d i n g t h e sc le ra as w e l l as th e o p t ic n e r v e
ula, and some staining of the optic disc. Ultrasonography
b e a d a n d re tin a ; a n d p e rh a p s a lo w e r p r o p e n s it y fo r m a llg - revealed a diffuse choroidal liimOr posluriorlv in an area of
nanl tra n s fo rm a tio n (Fig u re 14 - Th& posterior bow ing and thickening of lhe sclera (HJ. The c lin i­
In c id e n c e o f m e la n o c y Io n ia Is e q u a l i n a l l e t h n i c g r o u p s , cal diagnosis was diffuse sclerochoraidal m elanocytic nevus.
u n lik e u v e a l m e l a n o m a s th a t are m o r e c o m m o n in lig h t ly Because of suspected growth of Lhe lesion lhe eye was enu­
cleated in 1Э93. His-Lopalhologic examination revealed a
p i g m e n t e d i i n d i v i d u a l s. S p o n t a n e o u s n e c r o s i s o f a m e la n o -
highly vascular benign m uJanocylic mas-s involving the t ho-
c y t o m a , p a rtic u la rly w h e n it in v o lv e s th e o p tic n e rv e h e a d
noid and sclEra posteriorly and inferiorly (1 and higher-power.
o r c ilia ry b o d y , m a y cause p ig m e n t d e b ris in th e v itre o u s
f). The lumor was classified m icroscopically as a melanotic
th at m a y b e m is ta k e n fo r v itre o u s s e e d in g o f a m e la n o m a . schwannoma.
N e c r o s i s o f a n iris m e l a n o c y to т а m a y cause s im ila r c o n ­
1 Л - Н . I n j m C Tnibs-'1^1; I ;m d J , 1 r u m h -h i d d s и I a l M l |
fu s io n because o f a m acroph age re sp o n se lo n e c ro lic
tu m o r in th e a q u e o u s h u m o r a n d tra b e c u la r m e s h w o r k .
i h e re a s o n fo r th e ir p re d ile c tio n fo r s p o n ta n e o u s n e c ro s is
is u n k n o w n . Jr m a y b e t h a t t h e s e c e l l s a r e m o r e r e s p o n s i v e
D iffu se Scfero ch oro ida l M elan o cytic N evus
th a n u su al lo h o rm on al and i m m u n o lo g i c c h a n g e s . (S ee D iffu s e c h o ro id a l h y p e rp ig m e n ta lio n a n d th ic k e n in g m a y
d is c u s s io n of b ila te ra l d iffu s e uveal m e la n o c y tic p ro lif­ b e o b s e r v e d e i t h e r as a n i s o l a t e d f i n d i n g [ I ' l g u i t l 4 . О й ) o r
e r a tio n a s s o c ia te d w i t h s y s le m ic c a r c in o m a , b e lo w .) S lo w in a s s o c ia tio n w i t h e p isc le ra l p i g m e n t a t i o n [o c u la r m e ta -
lo ca l g ro w th can be d o c u m e n te d over years of obser­ n o c yto s i& J lh a l m a y e xte n d Lo i n v o l v e ip is lla te ra l s k in in
v a tio n ; m a lig n a n t tra n s fo rm a tio n Is rare bul known. lh e d is trib u tio n o f bra n ch e s o f tb e trig e m in a l n e rv e (o c u ­
C ]o m p lic a tio n s secondary lo c o m p re s s io n o f th e o p lic lo d e rm a l m e la n o c y to s is : n e v u s o f O t a } / '1 I h e life tim e risk
n e r v e fib e rs r e s u lt in g in a v is u a l fie ld d e fe c t, r a r e ly severe o f d e v e lo p in g u ve a l m e l a n o m a in a t j u c a s i a n w i t h o c u la r
enough t o Lose Jig h L p e r c e p t io n , c e n tra l o r b r a n c h re tin a l m e l a n o c y l o s i s is e s l i m a l e d to be a b o u t 1 in 400 [I'ig u r e
artery (F ig u r e L 4 . 0 & E H —| ) a n d v e i n o c c l u s i o n s a n d c h o r o i ­ 1 4 .0 9 ) . T h e ris k in n o n w h i t e s m a y a ls o b e h i g h e r b u l h a s
d a l n e o v a s c u l a r i z a t i o n , c a n o c c u r [ I ' i g u r e 1 4 . 0 6 1 ? —C J ) . n o l b ee n q u a n t ifie d .'
D iffu se Posterior C h o ro id o scle fa l M elanotic F 4 . (1 H I s o la t e d c h o r o i d a l m e l a n o c v t o s i s .

Schw annom a A—D: A 40-vear-old Indian female was referred t y ап oplom-

l>r. Gass had observed one g irl and re vie w e d fu n d u s cfLri^L fur evaluation of bilateral posleriOt-pole pigmented
p h o to g ra p h s and flu o re s c e in a n g io g ra m s o f a boy w ith I(^taciJTF. Thu pulienl was asymptomatic; she? denied any previ­
an id e n tic a l, p e c u lia r, d iffu s e p la t]u e lik e th ic k e n in g and ous episodes of blurred vision, photopsias, Г1оьПегь_. or pho­
tophobia. There? was no significant prior m cdical ui ocular
h y p e ip ig m e n ta tio n o f th e p o s te rio r a n d in fe rio r c h o F o id
history. Her visual acu ilv w]lh cjornec: Li on wan 20/20 bilater­
in one eye a s s o c ia te d w ith u ltra s o n o g ra p h ic and h is to ­
ally. bxLernal exa mi nation showed absence or eye iid or epi ­
p a th o lo g ic e vid e n c e o f p o s te rio r b o w in g and narked scleral pigmental ion with blue irides. fundus pholographs
L b i c k e n i n g o f th e c h o r o i d a n d sc le ra i n t h e m a c u l a r r e g i o n showing Hyinmelfic, I;Hi, and diffuse <horoida! hyperpigmen-
( E 'ig u r e 1 4 .0 7 ) 9 I h e b o y 's c o n d i L i o n , o b s e r v e d fo r se ve ra l Lalion :A and В .. Lale-phase fluorescein angiogram к bf the
y e a r s ., s h o w e d n o e vid e n c e o f g ro w Lh b u l h e d id d e v e lo p i i u.hI and lefl eyes e?;hiE)iLing absence of apparenl leakage or
re tin a l d e ta c h m e n t. The o p tic d isc in th e a ffe c te d eye
blockage 1C and L3l.

a p p e a r e d s w o lle n . T h e f u n d u s o f th e a ffe c le d e ye w a s m o r e [ThdHn Ки'г'-чзг 4fi. j|1. . \\ ilh [жгп i:1s k h i . :

p ig m e n te d th a n th e fe llo w eye, but th e re w a s no c lin i­

cal e vid e n c e o f m e la n o s is n c u li in th e a n te rio r segm ent
( E 'ig u r e 1 4 .0 7 A a n d tt). Flu o re s c e in a n g io g r a p h y re ve a le d
irre g u la r e a rly h y p e rflu o re s c e n c e and e vid e n c e o f som e th ic k fib ro v a s c u la r p la q u e on lh e t u m o r su rfa c e and Lhe

s t a i n i n g o x re r t h e in fe rio r p o r t io n o f lh e t u m o r , 'lh e eye m a r k e d v a s c u la rity o f t h e t u m o r , x e n o n p h o to c o a g u la tio n

w a s e n u c le a te d a n d h is to p a th o lo g ic e x a m in a tio n re v e a le d w a s a d v is e d b u t re fu s e d . I n 1 9 9 2 s h e w a s e x a m i n e d at Lhe

a d iffu s e th ic k e n in g o f th e c h o ro id a n d . scle ra p -o s tc rio riy W ills liv e E H o s p ita l, at w h i c h t im e t h e c lin ic a l fin d i n g s w e r e

and in f e r i o r l y b y a s p i n d l e ce ll n e v u s ( F i g u r e L 4 .0 7 C - L ) . unchanged except fo r p ro g re s s io n lo no lig h t p e rc e p tio n

In th e m a c u la r re g io n th e th ic k e s t p a n o f th e t u m o r w a s in th e rig h t eye. L n u c le a lio n w as a d v is e d . H is to p a th o lo g ic

a s s o c ia te d w i l h p r o m i n e n t p o s t e r i o r b o w i n g o f t h e sc le ra . e x a m in a t io n re ve a le d a m e la n o c y tic h a m a r t o m a in te rp r e te d

'Ih e r e w a s e v id e n c e o f s e ro u s re tin a l d e t a c h m e n t a n d p a p ­ as a m e l a n o t i c s c h w a n n o m a w i l h a p r o m i n e n t a n g i o m a t o u s

ille d e m a . lh e g irl w a s 14 years o ld when firs t e x a m i n e d c o m p o n e n t ( E 'ig u r e 1 4 .0 7 E a n d ] ) . ^

b y l>r. C a s s i n l a n n a r y 19 8 5 because o f recent w o rs e n in g Aw areness o f th es e d iffu s e h a m a r to m a Lous n e v o id

o f v is io n in th e rig h t e y e th a l h a d b e e n a m b l y o p i c s in c e m e la n o c y lic m a lfo rm a tio n s is im p o rta n t because th e ir

b irth , lh e f u n d u s f i n d i n g s in h e r rig h t e ve w e re id e n tic a l la rg e s ize a n d Lh eir p o t e n t ia l fo r lim iLe d g ro w th d u rin g

to th o s e in th e o th e r p a tie n t, e x c e p t f o r Lh e p re s e n c e o f a c h ild h o o d are lik e ly to c a u s e v is u a l s y m p t o m s in c h ild ­

s m a ll s u b re tin a l p a ra fo v e a l n e o va s c u la r m em brane and hood, and th e tu m o rs m ay he m is ta k e n fo r ft c h o r o i ­

m in im a l e vid e n c e o f re Lin a l d e la c h m e n l (Fig u re 1 4 .0 7 F dal m e la n o m a w ilh in tra s c le ra I e x t e n s io n . In te n s e and

and G ). I h e r e w a s i r r e g u l a r t h i c k e n i n g o f t h e s l i g h t l y e le ­ e xte n s ive la s e r tre a tm e n t and in som e cases irra d ia tio n

v a te d d a r k e n e d c h o r o i d in t h e m a c u l a a n d i n f e r i o r f u n d u s . m a y h e n ec es sa ry l o p r e v e n t to ta l re tin a l d e t a c h m e n t a n d

Ih e o p tic d is c w a s s w o lle n . U ltra s o n o g ra p h y re ve a le d a b lin d n e s s .

d iffu s e p o s te rio r m e d iu m -re A e c tiv e c h o ro id a l tu m o r th a t

w a s L h ic k e s l in lh e m a c u la r re g io n , w h e re th e re w as p o s ­
M ultiple C h o roid al N evi an d .Melanoma
te rio r b o w in g of th e sc le ra . U ltra s o n o g ra p h y su g g e ste d A sso cia ted with N eurofibrom atosis 1
th a t lh e c o n fig u ra tio n o f Lhe tu m o r w as s im ila r to lh a t A p p ro x im a te ly 3 5 '? 6 o f p a tie n ts w ith n e u ro fib ro m a to s is
p re v io u s Ey fo u n d h is to p a th o lo g ic a lEy in th e boy ( E :i g u r e w ill h a v e m u l t ip l e c h o r o id a l n e v i th a t i n s o m e p a tie n ts are
1 4 . 0 7 H ) . 'E 'h e c l i n i c a l d i a g n o s i s w a s c h o r o i d o s c l e r a l m e l a - b yp 3| ^ £ t L e i > t e d , > , ; 3 : 4 L' Ef d is c o v e r e d in c h i l d r e n , th e s iz e o f
n o c ylic h a m a r to m a . th e le s io n s a n d th e in te n s ity o f th e ir p ig m e n ta tio n m ay
In M arch 1991 sh e re turne d b e c a u s e o f fu r t h e r lo ss o f in c re as e w it h age. 'lh e in c re a s e d ris k f o r d e v e l o p m e n t o f a
v is io n in th e rig h t eye. Н е т v is u a l a c u ily w a s h a n d m ove­ uveal m e la n o m a in p a lie n ts w it h n e u ro fib ro m a to s is m a y
m e n t s o n l y a n d th is w a s L im it e d to t h e in fe r io r v is u a l fie ld . b e re la te d to t h e ir p r e d i l e c t io n f o r h a v i n g n o t o n l y m u l t i ­
S h e h a d a b u l lo u s re tin a l d e l a c h m e n l w i t h s h ift in g s u b r e t i­ p le n e v i, b u t i n s o m e cases a d iffu s e m e l a n o c y t i c h y p e r p l a ­
nal flu id . 'Ih e lu m o r d im e n s io n s w ere unchanged except sia o f t h e e n t i r e u v e a l t r a d r e s e m b l i n g c a f e - a u - l a i t l e s i o n s
fo r s o m e in cre ase in ils c e n t r a l e l e v a t i o n th at a p p e a re d lo o f th e s k in m a y b e p re s e n t (F ig u r e 1 4 .1 0 ) . G iv e n th e h ig h
re su lt fro m e xte n s ive fib ro u s m e ta p la s Lic changes o f th e p re v a le n c e o f n e u r o fib r o m a to s is 1, th e a s s o c ia tio n o f u vea l
p ig m e n t e p ith e liu m on its a n l e r i o r s u r fa c e . A fe w p ro m i­ m e la n o m a and n e u ro fib ro m a to s is i m a y b e re g a rd e d as
nent b lo o d ve sse ls w ere v is ib le near th e tu m o r s u rfa c e . c o i n c i d e n t a l ( F i g u r e 1 4 . 1 1 j . . ,|:
A n g io g ra p h y re ve ale d e xte n s ive s ta in in g in th e area of C h o ro id a l nevi in p a tie n ts w ilh n e u ro fib ro m a to s is
fib ro u s m e ta p la s ia . Ih is p o r L io n o f t h e t u m o r w a s tre a te d s h o u ld n o t b e m is ta k e n fo r R P E : n e vi (c o n g e n iLa l h yp er­
w i t h in te n s e , L o n g -d u r a tio n , 5 0 0 -m m a p p lic a tio n s o f a rg o n t r o p h y o f th e R P E a n d c o m b i n e d R P li a n d re tin a ! h a m a r ­
g r e e n la s e r. ' L h e d e t a c h m e n t p e r s i s t e d a n d t h e v i s u a l a c u i t y to m a s ), w h ic h m a y be a s s o c ia te d w i l h n e u ro fib ro m a to s is
w a s lig h t p e rc e p Lio n o n l y in A u g u s t 1991. Because o f th e (see F ig u re 1 2 .1 1 ) .
1 4 .1 Hi O c u l o t t o r m д[ m eJ п п а с у t(i s i s w i fh c h o n o ir fa I 14. E l U v e a [ m e I л n o m a w iLh n e u r o f i b r o m a t o s i s t y p e
m e l.m o m a , 1 lN F I).

A-D: A 5 4 - y e a r - o ld w h ile m an p re s e n te d w ith b lu r r e d A -D : A 15 -year-old w hile m ale w ilh NF1 was found lo
v is io n . E x te rn a l e x a m i n a tio n r e v e a le d le f t e y e l i d s , fo re h e a d , have Unilateral juvenile glaucoma. H e was managed medi­
and e p is c le r a l h y p e r p ig f n c n la t io n f A .I. F u n d u s w as d a rk in cally initially followed by trabeculectomy. A pipfnenLed1 iris
c o lo r w ith a d o m e - S .t iJf ljE d c h o r o i d a l m ass- s u g g e s t i v e or" c h o - lesion ihnL had increased in size was reported. The palienl
n u iН л I m e l a n o m a ( B l t h a t w a s c o n f i r m e d b y E Jlt r a s o n ir t r a p h y had numeruuH cafe-au-lail spols on his skin (Aj, and cuta­
В -scan (C ). E n u c t e a lio n c o n f ir m e d a m e la n o t ic c h o r o id a l neous netirorftbromai on his lefl forearm Lind right leg. His
m & l- a n o m a ( | } j . visual acuity was 20/20 in each eye. Intraocular pressures
were .lOnim Mg in the righl eye and I I mm H g in Ihe lefl eye
iA . In arid il ion Lo prominent со men I nerves and numerous
isch nodules in bolh eyes, an ill-defined pigmented iris
mass, emending frw n 2 o' clock Lo 4 o ' clock and measur­
ing 5 ^ 4 ^ 3 mm, was observer! -Uj. The enlire surface of
the iris stroma was diffusely seeded with tumor. G onioscopy
showed heavy pigmenlation o f Lhe trabecular meshwork.
1 4 .1 0 C h o r o i d a l n e v u s w i l h n e in ro m b ro m iito s is t y p e 1
Enucleation was performed in vie w o f diffuse seeding of Lhe
(NF
iris melanoma w ilh secondary glaucom a ICJJ. The sectioned
A and -В: A 10-year-old girl with NF1 . Note diffuse ch oro i­ globe showed lhe darkly pigmenled irii lesion exLendfng inlo
dal nevus :melanoLvLosisi HA I w hich resembles cal'e-au-lail lhe nasal angle, heavily pigmented Irabecular meshwork,
lesions of lhe skin (Sl. and tumor infillratinjj lh e temporal angle ( D ) .
! h! |□ггжI.и l r[ w iU i p*itnbil>Oli lr>: i Hr>n.iv.ir l'I il l. 1 '
CHOROIDAL MALIGNANT F4 . E2 Sub macn larch oro id al me la nomas.

MELANOMA A -С: Small malignanE melanoma of the choroid in a

22-year-old wnrilan wFrt noLed ph o tepsii and mild blurring
A m e la n o m a i n Els e a r l i e r s t a g e s o f d e v e l o p m e n l is J i i o s t ot vision. N o Ie I ho ring of pinpoinl suFirefinal Leaks and late
slaining 'Ы and (.j . 1lie Lumor showed evidence of enlarge­
Eifce ly t o b e o b s e r v e d c l i n i c a l l y w h e n it a r is e s i n o r n e a r l h e
ment within a few Friontfe and the eye was enucleaLed.
m a c u l a r a r e a . T h e r e il m a y с а а з е a s c o l o m a a n d p b o t o p s i a
Histopalbolujjically it №15 л spindle В melanoma.
p r o d u c e d b y i n v a s i o n о Г t h e re li n п o r lo s s o f v i s i o n c a u s e d
D -F: Localized serous detachment of the retinal pigment
by serous re lin a l d e ta c h m e n t. T h e c lin ic ia n w h o d is c o v ­ epithelium i Ь! PE I tiU s e d [>y sm iJI chorojda! melanoma lhal
ers a s m a l l p i g m e n t e d c h o r o i d a l l e s i o n a s s o c ia te d w i l h a mij=hl bo confuted w ilh я hom onhagi( delachmenl ot" the
m a c u la r d e ta c h m e n t s h o u ld n o t, h o w e ve r, c o n c lu d e (h a t K.FL and retina. Mote absence o f halo- o f blood at lh e margins
t h e l e s i o n is a m a l i g n a n t m e l a n o m a , s i n c e , as m e n t i o n e d ot" lhe lesion and lhe presence of lhe patches of urar1№ pig­
ment scattered over the surface o f the lesion and surrounding
p re v io u s ly , m a c u la r d e ta c h m e n t m ay occur o ve rlyin g a
Lhe base of the tmail K P t detachment la-rows, [J . There is
c h o ro id a l nevus. T h e m osl h e lp fu l s ig n s lh a l d is tin g u is h
н о т е serous doLadmion! of lhtf retina surrounding lh e m ela­
□ s m a ll c h o ro id a l m e la n o m a f r o m a n e v u s are: ( I ) g l o b u ­
noma. AriHio^rapFty shows imerise fluorescein staining of lhe
la r e le v a t io n o f t h e le s io n o f 3 m m o r m o re : [2 ] m u ltip le sub-К l-^E exudate (£ and f . The patches of orange pi ц т t-пI
areas o f o r a n g e p i g m e n t d e p o s itio n o v e r th e t u m o r sur­ appear as non fluorescent spols on lhe angiografH. Note lhe
fa c e ( H g u r e 1 4 . 1 2F>)r ( 3 } s e r o u s r e lin a l d e t a c h m e n t i n ( h e small pinpoint-sized hyperfluorescent spots Narrows) an Lho
a b s e n c e o f d n .is e n or e vid e n c e o f c h o ro id a l n e o v a s c u l ar- surface of lhe tumor. (Com pare with hislopaLhokjrgv in Hgure
14.13 A and B.l
iza lio n ; (4 ) e vid e n c e o f l u m o r b re a k in g th ro u g h B r u c h 's
m em brane: and (5 ) flu o re s c e in a n g io g r a p h ic e v id e n c e o f Laser photocoagulation treatment of small choroidaE
m u ltip le p in p o in t le a k s lh a l in c re as e in s ize d u rin g lh e melanoma.
c o u r s e o f a u g i o g r a p h v o n t h e s u rfa c e o f t h e l u m o i (I'ig u r e tc-l: In S o te m iie r I S S3 inis 5 it-year-old man noted, a para-
1 4 .l 2 B r C , a nd cenlraF scolom a associated w ilh exudalive retinal delach-
A n a ly s is o f C o lia b o ra liv e O c u la r M e la n o m a S tu d y
merri caused by a partly pigmented cFtoroidal melanoma
tFial harJ extended through Firuc.hrs membrane :n two fireas
[ C O M i ) d a ta su ggests lh a l lh e m a j o r i t y o f t u m o r s e n ro lle d
iarrows.. C^. Го produce f.horoidaI atrophy around the tumor,
in th e o b s e r v a tio n a l s m a ll-m e la n o m a s lu d y w ere c h o r o i­
inlense, t i.V and 1-second argon green 500- and 1000-mm
dal nevi ra lh e r th a n iru e m e la n o m a , as m o r e th a n applications w ere и-нег! to surround Ihe margin of Lhe iLimor
o f such tu m o rs d id n o l g ro w (w ith o u t tre a tm e n t) o ve r a I.H). Two weeks Eater similar laser applications w ere used lo
p e r i o d o f 5 y e a r s . 1 " ll is p r e f e r a b l e l o c la s s ify s m a ll c h o ­ Lreat Lhe entire surface ot" the lumor. ftjrly-three months laler
ro id a l m e la n o m a (C O M S s ize d e fin itio n o f 5- 1 6 m m in a placoid, irregularly pigmented scar remained. Eleven years
b a s a l d i a m e t e r a n d le ss t h a n 2 . 5 m m in h e ig h l) as in d e t e r ­ later1 ihere hat I been no further rtic urrence ol" lh e lumor, lhe
patiercL had no evidence o f metastasis, and die visual acuity
m i n a t e m e l a n o c y t i c l u m o r " 1" r a t h e r t h a n s m a l l m e l a n o m a ,
in lhe lefl eve was
la rg e n e v u s , s u s p ic io u s n e v u s , o r d o r m a n t m e l a n o m a .''" 4'1
It c a n be a s s u m e d th a t lh e s ize c a le g o ry o f in d e te r m in a te
Le sio n s ( J M I.) in c lu d e s an a s -ye l u n d e te rm in e d p ro po r­
tio n o f la rg e c h o r o id a l n e v u s , s m a ll c h o r o id a l m e l a n o m a ,
o r even tru e i n t e r m e d i a t e l e s i o n s . 4,1' S e v e r a l a u t h o r s h a v e
trie d lo id e n tify q u a lita tiv e s u rfa c e fe a tu re s lh a l p re d ic t
th e lik e lih o o d o f g ro w lh su g g e stive of m e l a n o m a . ?
R e a p p ra is a l o f th e p u b lis h e d C O M S d a ta has re v e a le d lh a l
th e p re s e n c e o f o ra n g e p ig m e n ta t io n s ig n ific a n tly p re d ic ts
r i s k o f g r o w l h . ■' A b n o r m a l i n t r i n s i c c h o r o i d a l v a s c u l a t u r e ,
as o b s e r v e d b y i n d o c y a n i n e g r e e n , m a y a ls o b e p r e d i c t i v e
o f g r o w l h r i a k ^ 1^
 At p re se n t, lh e m anagem ent of EM L (s m a ll c h o ro i­ F4 . [3 C M m c o p a t h o l o g i c c o r r e Ia t i o n s o f m e l a n o m a s .

dal m d a n D m i] re m a in s c o n tro v e rt] in th e absence o f

A and В: Com pare w ilh F-i^ure M.12 D-h. NoLe serous
d a ta fro m a ra n d o m ize d c lin ic a l tria l. 41 o J (t m ust be delachmunl of iht' retinal pigmerfl upi I helium [RPE) : black
e m p h a s ize d th a t o n e c a n o n l y a tt r ib u t e a n e s t im a te d risk arrow. A } and chim p □( orange p i ^ o r l (black and white
to a g iv e n [ M L d e p e n d in g u p o n t h e p r e s e n c e o f " r i s k fa c ­ nrruwH. A rind Б ■composed of either macrophages 1iI led w ill:
tors" p re d ic tiv e of g r o w t h . ' 1'' Th e re fo re , c a u tio n s h o u ld epithelial cel] pigment or hyperplastic pigmem epiLheliurt
Overflying n sSftidle 15 m pi arom a.
he e xe rc is e d in m a k in g a d ia g n o s is o f a s m a ll c h o ro id a l
С and D : Nonpi^m enled juxta papillary meNutoma simu­
m e la n o m a tn th e absence o f d o c u m e n te d g ro w th , '['h e
lating benign subretinal fibrovascular proliferaLion or
tre a tm e n t o p tio n s o f p ro m p t tre a tm e n t versus observa­
choroidal osteoma. It grew And the eye whs eru clealed.
tio n to docum ent g ro w th p rio r to tre a tm e n t s h o u ld be
F IIstupathdldgic exam inalion revealed a spindle cell m ela­
c le a rly d isc u ss e d w it h th e p a tie n t. W i t h fe w e x c e p tio n s , th e noma lhal extended posteriorly Ihrough Ihe sclera (D)':
g r o w t h r a t e o f a m e l a n o m a is c o n s t a n t b u t t h e g r o w L h r a t e E—K: This healthy 31 -year-old wom an who was in her Iasi
o f d iffe r e n t m e la n o m a s va rie s w id e ly . S o m e w ill d e m o n ­ trim eter ot pregnancy noled mErtamorphopsia a rd a central
stra te g r o w t h w ith in a fe w m o n th s [Fig u re 14 .1 2 A )v buL
scotoma in Ihe right eye. She had a prominent p ig jre rle d
lumor o f lhe rigjil caruncte since childhood. Examination
3 years o r lo n g e r m a y be re q u ire d lo d e le c t, t h e g r o w t h
revealed □ local ized serous таси Гаг delachmum :upper
o f som e m e la n o m a s .' " As m e n Lio n e d tn th e p re v i­
arfowr E> at the superior margin o f a large elevaled hypopig­
ous se c tio n , Lhe d e m o n s tra tio n o f g ro w th , a llh o u g h lh e mented choroidal tumor (small arrejws, FJ( inferior lo lh e righl
s in g le m ost re lia b le s ig n o f m a lig n a n c y , m ay o c c a s io n ­ macuEa. There was a bone-corpuscular pa Hem o f migra-
a lly o c c u r in a b e iiig n c h o ro id a l nevus m c h ild re n and Иоп of pigmunL inLo lhe retina over the peripheral aspecl
y o u n g a d u l t s . 1 '' I f t h e m a c u l a r d e t a c h m e n l p e r s i s t s a n d t h e ot" lbe tumor and in a broad zone along IFie inferior border
c h o ro id a l le s io n re m a in s unchanged, lo w - lo m o d e r a Le­
ot" Lbe tumor extending to the ora serrala (low er arrow, E.
and Gj- There was a focal nodular area of extension ot" the
in Le n s ily argon p h o lo c o a g u la tio n a p p lie d to (h e area o f
Lumor through Bruch's membrane linage arrow, F. and white
flu o re s c e n t le a k a g e u s u a lly causes re s o lu tio n o f th e sub-
arrows, G ). UlLrasound revealed a medium-reflective chorol-
re tiita l flu id . O n ly th e le a k in g area s h o u ld be H e a le d ;
dal lumor w ilh prominent vase.ularily iЫ j . Histopal ho logic
no a tte m p t s h o u ld be m ade to d e stro y th e lu m o r. [S e e examination revealed a highJy vascular tumor composed
p re v io u s d is c u s s io n c o n c e rn in g tre a tm e n t of c h o ro id a l ol" r-elalively trenign spindle cells showing r o mitotic activ­
nevi w iLh re tin a l d e t a c h m e n t .) D u rin g pregnancy th e re ity -.1 and I V i l e uxLension ol the Lumor through LJruch^
is s o m e e v i d e n c e t h a t b e n i g n n e vi o r lo w -g ra d e m e la n o ­
membrane 'arrow, ! O verlyin g and surrounding lhu tumor

m a s m a y b e s tim u la te d to g ro w (F ig u re 1 4 .1 3 H - J ) .' l.a r g e

n e v i, Like c h o r o i d a l h e m a n g i o m a s a n d o ste o m a sr m a y be
firs t d e t e c te d d u rin g th e cou rse o f p re g n a n c y b eca u se o f
d e v e lo p m e n t o f an o ve rly in g serous re tin a l d e ta c h m e n t m any la rg e d ila te d b lo o d V e sse l? a n d was com posed of

[s e e F ig u r e s I 4 .1 5 J - ] ., and ] 4 . J Z t > | —L ) . E - 'i g u ie 1 4 . 1 3 [ f i —K ) b e n ig p -a p p e a rin g m e la n o c y te s s h o w in g no e vid e n c e of

illu s tra te s a p a tie n t w ho d u rin g th e th ird trim e s te r o f m i t o t i c a c tiv ity [I'ig u r e 1 4 .1 3 1 a n d J ) .

p re g n a n c y d e v e lo p e d b lu rre d v is io n c a u s e d b y a lo c a lize d JS ES lo p a lh o lo g ic a lly Lhe re tin a in fe rio r lo th e tu m o r

serous m a c u la r d e ta c h m e n t caused by 10 X Ю x 6m m w as m a rk e d ly d e g e n e ra te d a n d sh o w e d m ig ra tio n o f RFii

p a rtly p ig m e n te d c h o ro id a l Lum or th a t was a s s o c i­ in to lh e re tin a aroun d b lo o d v e sse ls [I'ig u r e 1 4 .1 3 K ) .

a te d w ith a fo c a l are a s u g g e s tin g e x te n s io tt o f th e t u m o r P re s u m a b ly th e pregnancy p la ye d a ro le ili c a u s in g

th ro u g h B r u c h 's m em brane, ih e u ltra s o u n d was a ty p i­ in c re a s e d Lum or v a s c u la r e n g o ig e m e tit and m a c u la r

cal in Lh a t t h e le s i o n a p p e a r e d m o d e r a t e ly re fle c tiv e w i t h d e ta c h m e n t/ '' Ef it h a d not been e n u c le a te d , it is l i k e l y

e vid e n c e o f p r o m i n e n t v a s c u la rity [E 'ig u r e I 4 .1 3 H ) . ih e th a t th e re tin a w o u ld h a v e s p o n ta n e o u s ly re a tta c h e d a fte r

p re s e n c e o f a la rg e z o n e o f K P K a t r o p h y a n d b o n e c o r p u s ­ d e l i v e r y o f t h e i n f a n t . "Iliis c a s e a n d t w o o t h e r cases illu s ­

c u la r in tra re tin a l m ig ra tio n o f KP£ lh a l e xte n d e d fro m tra te d in I'ig u r e 1 4 .0 4 d e m o n s tra te th a t b io m ic ro s c o p ic

th e in fe r io r e d g e o f t h e t u m o r l o t h e o ra se rrata in f e r i o r l y e vid e n c e o f t u m o r e xte n s io n th ro u g h H r u c h 's m em brane

su g g e ste d th a t th e t u m o r h a d b e e n p r e v io u s ly a s s o c ia te d a l o n e is n o L n e c e s s a r i l y a s i g n o f h i g h g r o w t h p o t e n t i a l o r

w ilh a l o n g - s t a n d i n g r e t in a l d e t a c h m e n t th a t h a d s p o a tla - m a l i g n a n c y . I n t h i s c a s e i l is p r o b a b l e th a t lh e e xte n s io n

n e o u s ly re s o lve d , [n s p ite o f th es e a ty p ic a l fe a tu re s fo r a th ro u g h B r u c h 's m em brane occurred m any years p re v i­

m e la n o m a , th e eye w as e n u c le a te d . Ih e t u m o r c o n ta in e d o u s ly d u r i n g th e a c tiv e g r o w t h p h a s e o f t h e L u m o r .
 C h o r o id a l m e la n o m a s w ifi o c c a s io n a lly u n d e rg o spon­ F4.E3 C o n tin u e d

ta n e o u s n e c ro s is a n d re g re ss io n ^ I'h i.s m a y o c c u r r a p ­
inferiorly I h e r e was ejtlnmsive pefleBeralion o f ih tj retina and
id ly a n d b e a s s o c ia te d W ith a p p a r e n t v itre o u s s e e d in g o r iп1тл retinal migration of RKL (K). The relinal dt!lachmei>L is
m ore s lo w ly o ve r a p e rio d o f y e a r s .' In s o m e p a tie n ts зп artifaL'L. These findings suygusL IЬлI Ibis was either a large
s p o n t a n e o u s n e c ro s is m a y be a s s o c ia te d w i t h p d b i a n te ­ meLinLxytit nu-vus or kfW-grgjde fneliniomd I Ьл I had Езеич>
rio r-c h a m b e r and v itre o u s jjfiffifo m a tln n ^ and e xu d a tive present lor rnariy years. LEr lell eye; RE, riyht eye: KR retinitis
p ig m e n to s a .
r e t i n a ] d e l a c h m e n l .1'1 T h e m a n a g e m e n t o f a p a tie n t p re­
s e n tin g w ilh e vid e n c e o f recent s p o n ta n e o u s n e c ro s is o f
a m e la n o c y lic lu m o r is d i f f i c u l t because o f th e d is tin c t
p o s s ib ility t h a t Lhe t u m o r m a y b e a m e l a n o c y t o m a ra th e r
th a n a m e la n o m a . (S e e p re v io u s d is c u s s io n o f m e la n o ­ tu m o rs 3 m m o r t h i c k e r is p e r h a p s t h e m o s t h e l p f u l a n c i l ­

c y t o m a .) B e c a u se Lhe p ig m e n te d m j l e r i a l th a l o fte n s h e d s l a r y tes( i n t h e d i f f e r e n t i a l d i a g n o s i s o f c h o r o i d a l t u m o r s . ' "

i n t o t h e v i t r e o u s is n e c r o t i c , v i t r e o u s b i o p s y o r f m e - n e e d l e I l i.s n o l o f h e l p in d i f f e r e n t i a t i n g m e l a n o c y t i c n e v i f r o m

b i o p s y is u n l i k e l y t o p r o v i d e a d e f i n i t i v e d i a g n o s i s . ' ” r>c i f m e l a n o m a s . R a d i o a c t i v e 3 2P is u n r e l i a b l e i n t h e d i f f e r e n ­

L h e l u m o r is r e l a t i v e l y s m a l l a n d t h e r e is g o o d v i s u a l f u n c ­ t i a l d i a g n o s i s o f m e l a n o m a s . .......... 9 C o m p u t e d t o m o g r a p h y

t i o n o b s e r v a tio n m a y b e a d v is a b le . S o m e o f th e re p o rte d m a g n e tic resonance, and c o lo r D o p p le r im a g in g are of

cases o f s p o n t a n e o u s r e s o lu tio n o f m e l a n o m a s m a y have l i m i t e d v a lu e in lh e d iff e r e n t ia l d ia g n o s is o f le s io n s s i m u ­

been th e re s u lt o f m is d ia g n o s is . B le e d in g in to th e sub- la tin g m e l a n o m a s . " ' " ' 14* T h e C O M S has re c e n tly r e p o tte d

iv L i:;,t l 'p .u 'c i i г . I■■ U u - vilre o u H c a u s 'd b ;. e ro s io n of th e lo w e s t in c id e n c e { 0 .4 8 % ) o f in c o rre c t c lin ic a l d i a g n o ­

th e c h o rio c a p illa ris b y a s m a ll m e la n o n u in th e macular s is o f t u m o r s i n e y e s e n u c l e a t e d b e c a u s e o f s u s p e c t e d m e l ­

area may re s u lt in a m is d ia g n o s is o f a b e n ig n d is c ifo rm anom as^ The a u t h o r b e lie ve s th a t th is Lo w in c id e n c e o f

d i s o r d e r . I,r S a lie n ts W ith p e rip h e ra lly lo c a te d m e la n o m a s i n c o r r e c t d i a g n o s i s is m o r e t h e r e s u l t o f g r e a L e r a w a r e n e s s

may o c c a s io n a lly p re s e n t b e c a u s e o f a re lin a l d e ( a c h m e n t o f th e c lin ic a l a p p e a r a n c e o f le s io n s p r e v io u s ly m is ta k e n

Lh a t a p p e a r s lo b e c o n f i n e d to th e c e n tr a l m a c u l a r area o r f o r m e l a n o m a s Lb a n t h e a v a i l a b i l i t y o f m o r e a n c i l l a r y le sts

be cause o f c y s to id m a c u la г e d e m a ."*''1'0 lh a t fo r th e m o s t part p la y a lim ite d ro le in p h y s ic ia n s '

Le s io n s o th e r th a n n e v i th a t m a y s im u la te a m a lig n a n t d e c is io n -m a k in g .

m e la n o m a in c lu d e : h e m o rrh a g ic d is c ifo rm d e ta c h m e n t H i s l o p a t h o Lo g ic a lly , m e l a n o m a s h a v e a v a r ia b le p r e d i ­

o f t h e !? [3L a n d re L i n a ( s e e E ' i g u r e 3 . 2 4 a n d 3 .2 6 ) , s p o n ta ­ le c tio n f o r c a iLs titg d a m a g e t o t h e o v e r l y i n g R P E a n d r e tin a

n e o u s s u p ra c h o ro td a l h e m o rrh a g e , c o m b in e d re lin a l and (fig u re 14.1 З А and B J. E h is i s d e p e n d e n t o n m any fa c ­

fiP t h a m a rto m a s (se e fig u re s 1 2 . 8 - 1 2 .1 0 ) , h y p e rtro p h y to rs, p a rtic u la rly th e ir c y to lo g ic c o m p o s it io n and g ro w th

o f th e R P E (see f i g u r e 1 2 . 0] ) . h y p e r p l a s i a o f t h e iI P h ( s e e m l e . J ' JI,d 5 - ™

fig u re s 1 2 .0 7 and 1 2 .1 4 A - С and H - L .) . s u b re tin a l iro n , T h e ra p e u tic ; c o n s id e ra tio n s fo r c h o ro id a l m e la n o m a

fo re ig n -b o d y g ra n u lo m a (se e fig u re 8 .1 1 C - E :) , v a rix of depend upon t u m o r s ize (s m a lE, m e d iu m , larg e : C O M S

th e a m p u lla , a n d p a rtly o r g a n ize d d is c ifo rm d e ta c h m e n ts c rite ria ), lo c a tio n ( m a c u l a rr ju x ta p a p illa ry , p e rip h e ra l),

o f th e R P £ a n d re tin a s e c o n d a r y t o a v a r ie ty o f c a u s e s (se e v is u a l a c u ity , p o t e n t ia l fo r v is u a l a c u ity , sta tu s o f th e o l h e r

fig u re 3 .3 0 ] 1 tc h a n g e s in p e r m e a b ility o f th e b lo o d eye, s y s te m ic sta tu s o f th e p a tie n ts ( c o m o r b i d i t y , m e ta s ta ­

ve sse ls w ith in d isc i F o r m ]e s io n s m ay o c c a s io n a lly cause s is), a n d p a t i e n t p r e f e r e n c e ."1 En g e n e r a l , s m a l l c h o r o i d a l

th e s e d is c ifo r m m asses to e n la rg e a n d sim u la te a m e la ­ m e la n o m a can b e o b se rve d to d o c u m e n t g ro w Lh p rio r to

nom a (se e Fig u re 3 .5 0 ) . S m a ll a m e la n o lie m e la n o m a s tre a lin e n t o r tre a te d w it h tr a n s p u p illa r y t h e m io lh e r a p y o r

a ris in g in th e p o s te r io r fu n d u s are o fte n m is ta k e n fo r fo c a l ra d io th e ra p y (e p isc le ra l p la q u e or p ro to n beam irra d ia ­

c h o ro id itis , c h o ro id a l n e o v a s c u la riza tio n w ilh o v e rly in g tio n ). l^ r m e d iu m -s ize d tu m o rs ra d io th e ra p y is t h e p r e ­

e xu d a tive d e ta c h m e n t, iu x la p a p illa ry e xo p h y tic c a p illa ry f e r r e d t r e a t m e n t . E n u c l e a t i o n is t h e t r e a t m e n t o f c h o i c e f o r

h e m a n g io m a s o f th e re tin a , c h o r o id a l h e m a n g i o m a s (se e la rg e -s ize d t u m o r s a n d fo r tu m o rs w ith n e o v a s c u Ia r g l a u ­

fig u re s 1 4 .1 5 a n d 1 4 .1 6 ) , o s t e o m a s [s e e fig u r e s 1 4 .2 0 a n d com a, opaque m e d i a , o r e x l r a o c u l a r e x t e n s io n . In excep­

1 4 . 2 1 ), or m e ta s ta tic c a rc in o m a (see Eig u re 1 4 .3 0 C - E ) . t i o n a l c ir c u m s ta n c e s , la rg e t u m o r s c a n a ls o b e tre a te d b y

f l u o r e s c e i n a n g i o g r a p h y is o f l i m i t e d v a l u e i n t h e d i f f e r e n ­ r a d i o t h e r a p y ( o n e - e y e d , p a t i e n t p r e f e r e n c e ) . E i n u c l e a t i c m is

tial d i a g n o s i s o f n o n p i g m e n t e d le sio n s s im u la tin g m a lig ­ a ls o c o n s id e r e d fo r m e d i u m - s i z e d t u m o r s w i t h p o o r v i s i o n

n a n t m e l a n o m a s ..'' 75 En t h o s e e y e s w i L h a m i l d l y e l e v a t e d (Le ss t h a n 20/400) o r Low p o te n tia l fo r im p ro v e d vis io n

p ig m e n te d le s io n w i l h o ve rlyin g serous flu id , llu o re s c e in ( m a c u l a r L o c a tio n , o p l i c n e r v e i n v a s i o n ) . S u rg ic a l re s e c tio n

a n g io g ra p h y is m o s t h e lp fu l in d iffe re n tia tin g a neovas- (tra n s s c le ra l) o r e n d o r e s e c lio n e ilh e r as s o le tre a tm e n t o r

c u litr m e m b r a n e fr o m e a rly g r o w th o f th e L u m o r. Several in c o m b i n a t i o n w i t h r a d i o t h e r a p y is a n a l t e r n a t i v e o p t i o n

p in p o in t h y p e rllu o re s c e n l d o ts of flu o re s c e in le a k a g e fo r th o s e m e d i u m - s ize d tu m o rs w h ic h carry a h ig h liv e ­

occurs d u e to b re a k d o w n in t h e Jtl1 L f r o m g ro w th o f th e lih o o d of v is u a l lo ss fro m ra d ia tio n re tin o p a th y /o p tic

le s io n [fig u re 1 4 .2 Л -C ), w h ile e a rly Lacy h y p e rflu o re s ­ n e u ro p a th y A d d itio n a l d e ta ils a b o u t Lhe m a n a g e m e n t o f

c e n c e is i n d i c a t i v e o f a n o v e r l y i n g C N V . M . E c h o g r a p h y f o r p a tie n ts w i t h c h o r o id a l m e l a n o m a are a v a ila b le e ls e w h e re .

 D e s p ite 1ш р ш № щ Ы $ in d ia g n o s is and lo ca l tu m o r F4. i -! Bilateral diffuse uvea! melanocytic pro!iteration.
c o n tro l u s in g e y e -s p a rin g te c h n iq u e s , im p ro ve m e n t in
A—С : This b5-year-old т т л п experienced blurred vision
uveal m e la n o m a s u rviv a l has п о I. b e e n o b s e r v e d ." Ib is in bolh eyes. tw o years previously sFie had ал ovarian car­
c u rre n t s itu a tio n u n d e rlin e s lh e n e e d f o r e ffe c tive m e th ­ cinoma incom pletely excited and was treated by irradiation.
o d s t o p r e d ic t a n d a d d re s s m ic r o s c o p ic m e ta s ta tic d is e a s e , Visual acuity w as 20/25 in both eyes. Fundus examination
ih e c y to lo g ic c la s s ific a tio n o f C a lle n d e r has unde rgo n e ;:i I'inil revealor nu.ii ph- sli^hliv duvaled piumunLrd
c o n s id e ra b le m o d ific a tio n and a m p lific a tio n d u rin g
Lumurs in lhe exLramacular areas and peculi.nr orange spots
ia nov/s.. H'i in ihe m acular areas. Anyio^raphv revealed
th e p a s t d e c a d e in a n e ffo rt lo p ro v id e b e tte r p ro g n o s tic
focal nireas of eark1 hyperlluorescence corresponding w ilh
in fo rm a tio n r e g a r d in g th es e tu m o r s ." ' a5L90 M ore re c e n tly ,
the orange spots iCj. Metastatic evaluation was negative,
p ro g n o s tic a tio n o f uveal m e la n o m a based upon tu m o r
th e palienL developed bilateral cataracts and retinal detach­
c y to g e n e tic a n d m o le c u la r assays has becom e fe a s ib le .'' ments. Hath eyes were treated w ilh externa I -beam irradiation
K a r y o t y p e a b n o r m a l i t i e s , i n c l u d i n g loss o f c h r o m o s o m e 3 and ca Lara cl extraction^ Subsequently nhe had bilateral enu­
(m o n o so m y 3 ) r lo s s o f frq , a n d g a i n o f c h r o m o s o m e Sq, cleations. Ten yean; afLer the onset or visual symptoms she
have a s ta tis tic a lly sig n ific a n t a s s o c ia tio n w ith in c re a s e d
had no evidence «I metastatic disease.
D-F: Histopathologic examination of a patient with benign
risk o f m e ta s ta tic d e a th .' " Gene e x p re s s io n p ro filin g
uveal m elanocytic proliferation and a systemic carcinoma.
by m ic ro array can a ls o b e u s e d to sort tu m o rs in to o n e
Note enlargement of Lhe ciliary b o d y mild thickening o f the
o f t w o s u b g r o u p s : Eess a g g r e s s i v e c l a s s 1 t u m o r s a n d c la ss uveal Lrat L by nonpi^mented Fjeni^n mela rtfijcyLes ( I- , and
2 lu m o rs w ith a h i g h e r r is k o f m e t a s t a s is .'1" ''" S u c h te c h ­ Focal pigmented LumelacLions !arrows, □ and E; composed
n iq u e s are a p p lic a b le to t u m o r s a m p le o b t a i n e d a fte r e n u ­ of partly necrotic melanocyles. Note relaNvc H|jarinjj o f the
c le a tio n o r re s e c tio n a n d e v e n a fte r fin e - n e e d le a s p ir a tio n choriocapil laris 13..
b i o p s y .''1 " ' T h e u l t i m a t e g o a l is t o d e v e l o p t a r g e t e d a d j u ­
G-L: This 74-year-old man developed progressive local
Reulz-leghers-like hyperpi^menled spots on lhe- lips 1C:,
v a n t t h e r a p i e s f o r p a t i e n t s a l h i g h r i s k o f m e t a s t a s i s . ,D|
penis il-tjr anti mucous membranes ot IFie moulh (! several
R a p id re s o lu tio n o f m e la n o m a s fo llo w in g e ith e r
nionLhs before developing progressive Severe loss of vinioi:
b ra c h yth erap y o r io n izin g irra d ia tio n u s u a lly in d ic a te s a
in bolh eyes. Examittalltth of the fundi revealed л leopard-
m ore ra p id ly g ro w in g m e la n o m a and is a s s o c i a t e d w i l h a 5pot hyperpigrnen tat ion and widespread depigmen Lat ion of
h ig h e r m o r t a lit y ." i S im ila rly a tu m o r th a t sh o w s m in i­ Lhe reLinal рэодтегИ epiLhelium in both eyes (J-Ll. There were
m a l d e c r e a s e i n s i z e a f t e r i r r a d i a t i o n is m o r e l i k e l y L o h a v e mirltjrale, variably sift’d, slightly elevated, pigmenled lesions
been a s lo w -g ro w in g m e la n o m a and is a s s o c i a t e d w i t h a
hc.illered in the Гипс!i Ij-Li. .V.edical evaluation discovered
adenocarcinom a of [he sigmoid colon. H is visual acuity
m o r e fa v o ra b le p ro g n o s is .
declined Lo lighl perception only in the rijjht eye and со uni-
in^ fingers in Ihe Sell eye. He had no Eurlhcf evidence ot" car­
BILATERAL DIFFUSE UVEAL cinoma unli] he developed widespread rnptaslalic carcinom a
ol the skin jlist FnefoTe his dealh 2t> months alter the otise.4
MELANOCYTIC PROLIFERATION ot" symptoms. HistupalFiolo^ic examination of die eyes con­
ASSOCIATED WITH SYSTEMIC firmed Lhe diagnosis ol" bilateral diffuse uveal m elanocytic
proliferation.
CARCINOMA
B ila te r a l d i f f u s e u v e a l m e l a n o c y tic p r o l i f e r a t i o n ( H D U M 3 * )
is an unusual syn dro m e o c c u rrin g in p re d o m in a n tly m ild uveal th ic k e n in g m a y b e o v e rlo o k e d a n d m a y b e d if­
e ld e rly p a tie n ts w h o h a v e d iffu s e u ve a l t h ic k e n in g th a t h a s fic u lt to de tec t w i l h u ltra s o n o g ra p h y . I here m a y b e m u l­
been a ttrib u te d Lo p ro life ra tin g , p re d o m in a n tly s p in d le - tip le fa in t o ra n g e sp o ts or p a tc h e s sca ttered th ro u g h o u t
typ e b e n ig n m e la n o c y te s in b o th eyes a s s o c ia te d w ilh a lh e p o s te rio r fu n d u s ( fig u r e 14.14B , M , and N J.J " At
c a r c i n o m a e l s e w h e r e i n t h e b o d y . ''■ l1 f,r l h e o n s e t o f v i s u a l th e lim e o f p re s e n ta tio n o r s o o n a fte rw a rd th es e p a tie n ts
s y m p t o m s m a y a n te d a te o r fo llo w th o s e c a u s e d b y th e sys­ d e v e lo p th e s in e qua non o f th e syn drom e: m u ltip le ,
te m ic c a rc in o m a . V is u a l l o s s is a s s o c i a t e d w i t h e ith e r o r s l i g h t Iу e l e v a t e d , p ig m e n te d c h o ro id a l L u m o rs s u g g e s tin g
b o t h r a p i d l y p r o g r e s s in g c a ta ra c t a n d Joss o f re tin a l f u n c ­ m u l t ip l e n e v i o r m e ta s ta tic m e la n o m a s sc a ttered t h r o u g h ­
t i o n . litis [a lte r m a y b e c a u s e d e ith e r b y d ire c t n u t r i t i o n a l o u t th e fu n d u s (fig u r e 14 . 1 4 A, K, l.-N ). E'o c a l p i g m e n t e d
or to xic dam age Lo Lhe o v e r ly in g re tin a and R P E or by a n d n o n p i g m e n t e d t u m o r s m a y d e v e l o p o n t h e iris . S ig n s
b ila te ra l s e c o n d a r y re lin a l d e t a c h m e n t . l h e d iffu s e u s u a lly o f irid o c y c litis m a y h e p re s e n t.
 1

L
 I n a re a s o f Lh e p o s t f i H d t f u n d u s t h a t lin a y a p p e a r o p h - E4.E4 C o n tin u e d

tb a lm o s c o p ic a lly re la liv e Ey n o rm a l, e a rly -p h a s e flu o re s ­

M -Х: This 72-year-oid гпччг w ilh д hjsJtary o f metastatic
c e in a n g io g r a p h y m a y s h o w a s in k in g ra th e r w id e s p re a d геплЁ cell счэгсмтопла fcj Lhe lung nolec: bilateral dimness ir
p a tte rn o f m u llip le Irre g u la rly r o u n d areas o f h y p e r f l u o ­ vit-ion over 4 w et1кн. The lung lumors w ere shrinking w ilh
rescence L h a l c o r r e s p o n d w i l h lh e o ra n g e sp o ts seen b io - sorafunib Ntixavar., a kinase Inhibitor used I о I real renarl a 'l:--
m i c r o s c o p i c a l l y , as w e l l as p i n p o i n t a n d p a tc h y areas o f hepatic caitinD m as. His vision was 20/40 and 2CV3-0. Licuh
flu o r e s c e in s t a in in g la te r d u r i n g t h e s tu d y (i'ig u r e L4 .14 C
вусч showed shallow sotous detachments associated w ilh
two types of pigmented lesions: some were mure pi дол е л led.
P - R ] . 1'' lh is d r a m a t i c a n g i o g r a p h i c p ic tu r e is a p p a r e n t l y
1-2 disc; art^as ir: size, Ihe others were fiaL i LJO—ЗОО 11m in
caused by th e p a lc h y d e p ig m e n ta lio n and d e s tru c tive
size and arranged in a le(jpajd-5fH>l paLlern ■:arrows M and
changes of th e p jp £ o ve rly in g th e re la tive ly in la c l cho- N . Tht1 choroirl was diffusely thickuncd on '.i I Ira sound. The
rio c a p ilE a ris and d iffu s e uveaE m e la n o c y tic in filtra tio n larger pi^menled lesions blocked Е Г и с л е ^ с е л с е on bolh flu­
[I'ig u r e 1 4 . 1 41']. A u lo flu o re s c e n c e s h o e 's d e c r e a s e d a u to ­ orescein and indocvanine angiography:: w hile lh e smaller
flu o re s c e n c e c o rre s p o n d in g to th e FtM d e s tru c tio n and lesions showed earEy hyperfluorescence along w ilh several
i n c r e a s e d a u t o f l u o r e s c e n c e i n t h e i n t e r v e n i n g a r e a s ( E - 'i g u r e pinpoinl hiyper fluorescent doLs in the <idjaccnl area and
leaked dye late (P—T}- AuloflLiarescence showed decreased
14.1411 a c id V ) . lh e presence o f s u b re tin a l flu id can be
Hulos'luorestence of the leopdra-spot lesions and increased
c o n firm e d by O C T [ E - 'i g u r e 14.14 0 ]. Lte c Lro re lin o g ra p h y
aulofluorescence in Ihe intervening areas (U a n d V ). A diag-
m ay show severe a b n o rm a litie s .™ U ltra s o n o g ra p h y i'i"-is ol p.ua neoplastic lesions ol bilaLeral diffuse uveal
m a y s h o w e v id e n c e o f d iffu s e , u s u a lly m ild th ic k e n in g o f m elanocylic proliferalion was made. H e received plasm a­
th e uveaE Lra c l. E H is to p a lh o lo g ic a lL y th e m e l a n o c y l i c ce lls pheresis three IFmes per week, vision improved to 2 0 /2 0 a n d
re s p o n s ib le fo r th e d iffu s e u vea l th ic k e n in g are re la tive ly 20/25 r and lhe serous dctlachments resolved. The larger pig­
E t y p o p i g m e n t e d p l u m p s p i n d l e cells w i t h a b e n i g n a p p e a r ­
mented lesions now begafi Lo rosemljle lhe smaller ones w ilh
Lhe ]eopard-sf>ol pa I tern :arrow W and X).
ance. M tlo lic fig u re s a re ra re . R e la t iv e s p a r in g o f ( h e c h o -
r i o c a p i J la ris a n d e x L e n s iv e p a t c h y a re a s o f d e s t r u c t i o n a n d [M - X , сииМ^чу ill Ur. Jjrn p o i.)

d e g e n e r a tio n o f th e p ig m e n t e p it h e liu m a n d re tin a l re c e p ­

to r ce lls are c h a ra c te ris tic fe a tu re s ( E 'ig u r e I4.E4E-). The
m u I Li f o c a l m o r e e l e v a t e d a n d p i g m e n l e d c h o r o i d a l l e s i o n s a rise f r o m a com m on o n c o g e n ic s tim u lu s . Ih e c y to lo g ic
are c o m p o s e d o f la rg e ro u nd o r p o ly g o n a l m e la n o c y te s , s tru c tu re o f th e m e la n o c y te s c o m p o s in g th e uveal ih ic k -
s m a lE n u c le i, a n d a b u n d a n t c y to p la s m packe d w ith m e la ­ e n i n g a n d t h e re Ea tive s p a r i n g o f l h e c h o r io c a p ilE a r is s u g ­
n in [I'ig u r e 1 4 . 1 4 D a n d Ё } , N e c r o s i s ts p r e s e n t i n m o s t o f gest th a t d iffu s e c o n g e n ita E u v e a l m e la n o c y lo s is m a y b e a
th e s e le s io n s , lh e c ilia ry b o d y , in c lu d in g th e c ilia ry p r o ­ p re -e x is tin g re q u ir e m e n t fo r th e d e v e lo p m e n t o f this s y n ­
cesses, is th ic k e n e d by in filtra tio n of m e la n o c y lic ce lls d r o m e . T h e c o n c e p t th a t h o r m o n a l s u b s ta n c e s re le a s e d b y
and th e le n s s h o w s ca ta ra c to u s ch a n g e s. A lt h o u g h som e c e rta in c a r c in o m a s are r e s p o n s ib le fo r s t i m u l a t i n g p ro lif­
a u th o rs h a v e c la s s ifie d th is uveal in filtra tio n as a m e la ­ e ra tio n . fo c a l m e la n in p ro d u c tio n , and n e c ro s is in th e
n o m a , m o s t h a v e fa v o re d a b e n ig n c la s s ific a tio n . uveal m e la n o c y te s , as w e lE as c a u s in g im m u n e -in d u c e d
'I'h e s e p a t i e n t s u s u a l l y d i e b e c a u s e o f m e t a s t a t i c c a r c i­ d e s tru c tio n o f th e and r e l i n a , is a n a ttra c tive b u t as
n o m a w i L h i n 2 y e a r s o f t h e o n s e t o f v i s u a l s y m p t o m s , '['h e y e t u n p r o v e n t h e o r y . 111, L0S' ° 6 lh is c a n c e r-a s s o c ia te d m e la -
lo n g e s t s u rv iv a l to d a te is 6 ..т years fo r a w o m a n w hose n o c y l o p a L h y m a y be a s s o c ia te d w i l h s e ve re lo ss o f v is u a l
p rim a ry c a rc in o m a W as o v a ria n and w ho had b ila te ra l Ju n c tio n and severe e le e lro re lin o g r a p h ic changes b e fo re
e n u c le a tio n s because o f u n c o n tro lle d m e l a n o c y tic p r o l i f ­ lh e d e v e lo p m e n t of re tin a l d e ta c h m e n t. T h is su g g e sts
e r a tio n , re lin a l d e ta c h m e n t, a n d p o s t irra d ia tio n c o m p lic a ­ t h a t Lhese p a t ie n t s m a y s h a r e s o m e p a th o g e n e tic fe a tu re s
t i o n s . Il:' A n o t h e r p a tie n l w h o had b ila te ra l e n u c le a tio n s in c o m m o il w ith th o s e w h o d e v e l o p a c u te lo ss o f re tin a l
has s u rv iv e d 5 years w it h o u t d e v e lo p in g e v id e n c e o f л p ri- re c e p to r e le m e n ts in th e p re s e n c e o f a s y s le m ic c a r c in o m a ,
m a r y r c a n c e r . 1:5 T h e p r i m a r y t u m o r in wom en is u s u a l l y lh e s o -c a lle d c a n c e r-a s s o c ia te d re tin o p a th y syn drom e
c a r c i n o m a o f t h e u t e r u s o r o v a r y a c i d i n m e n is c a r c i n o m a (see d is c u s s io n in C h a p te r 1 3 } . ' ^ | | Я " J S tim u la tio n of
o f th e lu n g s o r a re tro p e rito n e a l c a rc in o m a o f u n c e rta in p ro d u c tio n o f m e la n ic t by m e la n o c y le s in lh e s k in and
o rig in . N one o f th e p a tie n ts to d a te have had e vid e n c e m u c o u s m e m b r a n e s o f t h e m o u l h a n d g e n it a lia m a y a ls o
o f m e ta s ta tic m e l a n o m a . 3 t Is n o l. known w h e th e r o c c u r o c c a s io n a lly in th es e p a l ie n t s a n d p ro d u c e a c lin i­
Lhe in tra o c u la r p ro life ra tio n is a r e s p o n s e lo su b sta n c es c a l p i c t u r e s i m u l a t i n g t h e ETe u t z - J e g h e r s s y n d r o m e ( E ' i g u r e
re le a s e d b y lh e s y s le m ic c a r c in o m a o r w h e t h e r t h e y b o t h I 4 . 1 4 t ; - L } . l0hi: ju
 The te rm B D U M P does not f u l l y d e s c rib e e xtra o c u la r F4 . E ^ Cho rorda I h e litany ionia .
р л гд й е о p la s tic m a n ife s ta tio n s o f (h e d is e a s e , and g ive n
A -E: S e ro u s d e ta c h m e rit o f th e m a c u l a s e S D n d a r y lo c h o -
t h a l e x t r a o c u l a r m a n i f e s t a t i o n s m a y o c c u r Lji a b o u t 2 t № b o f rt>idill h e m a n g l q f r i a in д 4 7 - y e a r - o l d w o m a n c o m p l a i n i n g o f
c a s e s .. l h e a u t h o r h a s s u g g e s t e d p a r a n e o p l a s t i c m e l a n o c y l i c r e c e n l o n s e l o f b l u r r e d v i s i o n in L h e T i g h t e y e . h o l t 3 I h o m o l -
p r o life r a t io n b e u s e d t o d e s c rib e ih is u n i q u e p a r a n e o p la s ­ l l e d , y e l k m - isb a p p e a r a n c e d I her t u r E a c e erf I h e L u m o r ' ' a r r o w ,
t i c d i s e a s e .120 A l . w h i c h w a s lo c a te d S fflb fe ro ta n p D ia t id th e o p tic d is c .
A rte rio v e n o u s - a n g io g r a m s s h o w e d Lhe p re s e n c e o f m u l-
The d iffe re n tia l d ia g n o s is in c lu d e s H a r a d a 's d is e a s e -
L i p l e b l o o d vessels; i n IFh s l u m o r ( B ) . L a l e r - p h a s e a n g i o g r a m s
id io p a th ic u v e a l e ffu s io n , m e ta s ta tic c a r c in o m a , m e ta s ta tic
s h o w e d s t a i n i n g o f I b e s u r f a c e o f the* l u m o r f O . A r j ^ o n p h o l o -
m e la n o m a , re a c tiv e ly m p h o id h yp e rp la s ia of lh e uveal
c o a g u la tio n w a s p la c e d o n lh e t u m o r s u r fa c e ( D ) . iiuve ra l
tra c t, -a nd b ila te ra l m u llic e n tr ic o r d iffu s e p rim a ry uveal
m o n L h s la le r th e s e r o u s d e t a c h m e n t h a d r e s o l v e d -Ll.
m e l a n o m a s . " '1 F and G : H e m a n g i o m a o f Ih e c h o r o i d w it h s e ro u s a n d lip id
The r e L i n a l d e t a c h m e n t i n t h e s e p a l i e n t s is n o n r e s p o n ­ eK udalivrs r n a t u l o p a l h y in a 4 0 - y e a r - o l r J w o m a n bel'orts I}
sive lo c o rtic o s te ro id s , a n lim e la b o tile s , and irra d ia tio n a n d after ( C ) la s e r p h o t o c o a g u E a L i o n . N o t e the in c o m p le te
re so lu Sio n o l th e Lip id e x u d a t e . H e r v is u a l a c u iE y i m p r o v e d
L r e j t m e n l . 1' " P l a s m a p h e r e s i s m ay he u s e fu l i f s te ro id s
a n d a n t i m e t a b o l ties d o n o t h e l p . I n d e s p e r a te ca se s u s e o f
From 20 /2 CKJ to 20 /2 5 .
H a n d I, lu K la p a p illa ry c h o ro id a l h e m a n g i o m a ( a r r o w s ) in
p a is p l a n a v i H e c to r .ty a n d H u i d - s i li c o n e e x c h a n g e to t a m ­
a 4 7-ye a r-o ld пил who w a s treated u n s u c c e s s fu lly fo r 1 0
ponade th e re tin a in p la c e m a y b e s u c c e s s fu l in r e s to r in g years fo r a re cu rre n l se ro u s d e t a c h m e n t o f lb e m a tu fa iff
a m b u la to ry v is io n .™ unknown cause. H i s visu a l a c u ity w as 2Q/200. Th ere w as
e xte n s ive c yslo id d e g e n e ra tio n o f Lhe re tina h u l n o se ro u s

CIRCUMSCRIBED CHOROIDAL d e l a c h m e n l o f L h e m a c u l a ( H ) . H i s v i s u a l loss w a s I h e res a IL

o f p e r m a n e n t d e g e n e r a L i v e c h a n g e s in tFie r e t i n a s e c o n d a r y
HEMANGIOMA___________________ lo m u l t i p l e г а с u r r e n c e s o i s e r o u s re lin a l d e t a c h m e n t . N o te
re d flisii-o ran g e c o lo r ot lb e lu m o r a n d s m a ll, r o u n d , y e llo w
C a v e rn o u s h e m a n g io m a o f th e c h o ro id is a b e n i g n d e v e l ­ d e p o s its o f e x u d a t e in l h e o u t e r c y s tic s p a c e s o f Lhe re lin a .
o p m e n t a l t u m o r - - 3-' t h a t t y p i c a l l y o c c u r s e i t h e r as a l o c a l ­ V e n o u s - p h a s e a n g i o g r a m s h e w e d e a r l y s l a i n i n g o f ibi? U i m o r
ize d tu m e fa c tio n , u s u a lly in p a tie n ts w ith o u t other s u rfa c e . O n t v h o u r a n g io g r a m s h e lv e d m u lt ilo c u la le d p a Lto rn
ol" d y e i n d i c a l i v e o f c v s l o i d d e g e n e r a L i o n a n d e d e m a ot" L h e
v a s c u la r m a lfo rm a tio n , o r as a d i f f u s e t h i c k e n i n g o f t h e
r e l i n a ll.i.
c h o ro id in p a lie n ts w ith S tu ig e -W e b e r syn dro m e (se e
|—L : D u rin g lh e e i^ h lh m o n lh o f pregnancy t h is 3 2 - y e a r -
nest s u b s e c t i o n ) . ' ' - j ! J -!> - L 111 Lo c a lize d cavernous hem an­
o ld wom an 'lo le d m e La m o rp h o p sia caused l>y serous
g io m a s o f th e c h o r o i d are ra re ly d e te c te d b e fo r e th e th ir d m a c u l a r d e l a c h m e n l i b l a c k a n d w h i l e a r r o w s . J) a n d a p r e ­
d e c a d e o f Life . T h e y o c c u r n e a r l y a l w a y s a s a s o l i t a r y t u m o r vio u sly u nd e te cted h e m a n g io m a o f c h o r o i d JbEacfc a r r o w s ,
in one eye, a lth o u g h b ila te ra l in vo lv e m e n t o c c a s io n a lly Гi. A n g i o g r a p h y s h o w e d e v i d e n c e o f З а г ^ е v a s c u l a r spaces
o c c u r s .1:51 I h e i r r a t e o f g r o w t h is p r o b a b l y m a x im a l d u r­ w i l l i m t h e l u m o r a n d Ia le s l a i n i n g o n i1 s s u r f a c e !K a n d L : .

in g th e n o r m a l g r o w t h p e r io d o f th e in d iv id u a l. B y a d u lt ­ T h e relina l d e la c h m e n l re s o lv e d a n t! v is u a l fu n c tio n re tu r n e d
Lo n e a r n o r m a ! d u r i n g l h e e a r l y p o s l p a r l u m p e r r o d .
h o o d th e h e m a n g io m a m a y cause s e c o n d a ry d e g e n e ra tiv e
and p ro life ra tive changes in Lhe o ve rly in g p ig m e n l e p i-
Lh e l i u m a n d cystic e d e m a a n d d e g e n e r a L i o n o f t h e r e t i n a .
Ih e s e c h a n g e s as w e ll as th e d e v e l o p m e n t o f s o m e v a r ic o s ­
ity a n d c o n g e s tio n o f th e la rg e v a s c u la r c h a n n e ls a re p r o b ­
a b ly re s p o n s ib le fo r th e m in o r e n la rg e m e n t o f c h o ro id a l
h e m a n g i o m a s d e m o n s t r a t e d i n l a t e r l i f e . ' 1-' 14 U n le s s th e
t u m o r is l a r ^ e a n d is l o c a t e d d i r e c t l y i n t h e m a c u l a r a r e a ,
p a t i e n t s a re u s u a l l y a s y m p t o m a t i c u n t i l m i d d l e o r Later life
(a ve rag e age a p p r o x im a te ly SO y e a rs ), w h e n th e y d e v e lo p
serous re lin a l d e t a c h m e n t Lhat s p re a d s f r o m th e edge of
t h e t u m o r i n t o t h e m a c u l a r a r e a ( l - ' i g u r e 1 4 . 1 5 ) . Ije&s o f t e n ,
th e s e tu m o r s m a y be d is c o v e re d as a n in c id e n ta l fin d in g
by Lhe p h y s ic ia n o r b y Lhe p a tie n t, w h o o n c o ve riEtg th e
e ye , n o tic e s a s lig h t d is to r tio n o f c e n tra l v is io n c a u s e d b y
th e t u m o r 's p re s e n c e in th e m a c u la b e fo re Lt c a u s e s any
s i g n i f i c a n t a l t e r a t i o n i n t h e o v e r l y i n g R P l i a cid r e t i n a .
C r f t n n t f i s c r i i t f i i ' С Т г с р г в н iVtJ1 W l ' d j . m Д Й Л ш [ 2 0 7
 M any o f th es e p a tie n ts a re re fe rre d with th e in c o rre c t F4.[fi C h o ro id a l hemangioma.
d i a g n o s i s o f c e n tr a l s e r o u s c h o r i o r e t i n o p a t h y , c h o r o id itis ...
A -F: Lost of central and superior field of vision- Laused by
d is c i f o r m d e g e n e ra tio n m e ta s ta tic c a rc in o m a , m a lig n a n t a previous long-standing retinal delat'hmcnl esrencfoftg infe-
m e la n o m a , or rh e g m a lo g e n o u s d e ta c h m e n t. Ebe hem ­ ::nHy 1гйт a t:horoidal hemangiornq.; Mtite marked hyper­
a n g io m a s are ly p ic a lly ro u nd or oval, s lig h tly e le va te d , plasia of lhe pigmenL cpitFmlium DYtrfying the Uimor >\i as
o ra n g e -re d tu m o rs w ith an in d is tin c t b order (fig u re well аы dependent /ones of pigment BpiLhelial atrophy and
14 . IS A * ft H j and J). Ih e y a re m o s t e a s ily d e te c te d with
inlra retinal migration af pigment inferior to lh e tumor (A—Ct.
A njj iogr a m showed sLaining o f suluelinal lissiue eve dying
b in o c u la r in d ire c t o p h th a lm o s c o p y . They u s u a lly m ea­
Lhe liemaHgkjma and a io n e t>l" depigmentaLmn larrtiW, [J.
sure 2 - 10 d is c d ia m e te r s in s ize . M o s t o f th e t u m o r s are
that extend in a flask-Eike shape to the ora serrata Fnierrorly.
c e n te re d in th e p a r a m a c u la r area, b u l m a y e x te n d in to th e
UlLruiionography bhuwed highly reflrctiyu tiffiiOr lvpical of
e d g e o f th e c e n Lra l m a c u la r area. S o m e are iu x la p a p illa r v hemangiuma (E anil F).
in l o c a t io n . O t h e r s m a y h e lo c a te d o n t h e n a s a l s id e o f th e G and H : Histopithojoaff af cavernous hemangioma ot" lhe
o p t i c d i s c .1 ' 1 En m o s t cases t h e re tin a l d e ta c h т е л L e x t e n d s choroid; Note SBCond.ary (.vslic degeneration of Lhe fcweHyirtg
aw ay fro m th e m a rg in s o f th e lu m o r . The re tin a o v e r ly in g
relina 'C j. l-figh-power vk+w i Л 1 hlmws tystic degeneration
of lhe reLina and hyperplasia and metaplasia ol Lhe relina
th e tu m o r is u s u a lly th ic k e n e d by c ystic d e g e n e ra tio n .
pigment epilhelium on the turner surface.
C o m p le te s e p a ra tio n o f th e t u m o r fr o m th e o v e r ly in g re t­
in a b y a se ro u s d e ta c h m e n L occurs in fre q u e n tly . V a r y in g
a m o u n ts o f s p lo tc h y y e llo w is h m a te ria l lie b e t w e e n th e
tu m o r a n d w ith in t h e c y stic spaces o f t h e o v e r l y i n g re lin a
(I ' i g u r e 14.1ПЛ . К and Н ]. ] iy p e rp ig m e n ta tio n caused by
f i P L h y p e r p l a s i a is r e l a t i v e l y u n c o m m o n b u t , w h e n p r o m i ­ I'a tie n ls with c h o ro id a l h e m a n g io m a s a s s o c ia te d with
n e n t.. m a y c a u s e a m i s d i a g n o s i s o f a m e l a n o m a o r d is c i­ o v e rly in g c ystic changes and serou s d e ta c h m e n t dem ­
f o r m scar, S o m e p a t i e n t s d e v e l o p a b u l l o u s d e t a c h m e n t o f o n s tra te fie ld d e fe c ts c o rre s p o n d in g w ith th e s ite o f t h e
Lhe re tin a in fe r io r l o th e t u m o r at th e tim e o f p r e s e n ta tio n . tumor and th e s u r r o u n d in g d e t a c h m e n t . N e r v e fib e r b u n ­
O t h e r s w i l l s h o w la rg e f l a s k - s h a p e d a re a s o f a t r o p h y o f t h e d le d e fe c ts h a v e b e e n r e p o r t e d b u t are u n u s u a l.
RPH w ith a b o n e c o rp u s c u la r p a tte rn o f p ig m e n ta tio n in lb e c h a ra c te ris tic a n g io g ra p h ic fin d in g s in c h o ro id a l
th e o v e r ly in g re tin a e x t e n d in g in fe rio rly f r o m th e m a rg in s h e m a n g io m a s are: ( 1) a p a tte rn o f flu o re s c e n c e in d ic a tiv e
o f th e t u m o r (fig u r e 1 4. ] and C ). Ilie s e areas a re i n d ic ­ o f la rg e v a s c u la r c h a n n e ls c o r r e s p o n d i n g l o t h e lo c a t io n o f
a tive o f p re v io u s lo n g -s ta n d in g re tin a l d e t a c h m e n t w ith l h e L u m o r in th e p n e a rte ria l a n d a rte ria l p h a s e o f a n g i o g r a ­
a tr o p h y o f th e o u te r re tin a l la y e rs p e rm ittin g m ig ra tio n p h y ( F i g u r e 1 4 . E 5 K ) ; ( 2 ) w id e s p r e a d a n d ir r e g u la r areas o f
o f p i g m e n t e p i t h e l i a l c e lls i n t o t h e o v e r l y i n g r e t i n a . W h e n flu o re s c e n c e s e c o n d a r y t o d iffu s e le a k a g e o f d y e f r o m th e
Lbe h e m a n g i o m a is s m a l l , t h e s u b t l e e l e v a t i o n a n d h y p e r ­ s u rfa c e o f th e l u m o r r a n d ( 3 ) a d iffu s e m u lt ilo c u E a le d p a t ­
flu o re s c e n c e m a y be m is s e d a n d a m is d ia g n o s is o f c h r o n ic te rn o f flu o re s c e in a c c u m u la tio n i:t t h e o u t e r r e t i n a c h a r ­
id io p a th ic c e n tra l s e ro u s c h o r io r e tin o p a th y m a y b e m a d e . a c te ris tic o f p o ly c y s tic d e g e n e r a t i o n a n d e d e m a d u r i n g t h e
S te r e o s c o p ic i m a g i n g h e l p s Lo d e t e c t t h e e l e v a t i o n o f ( h e la te r stages o f a n g i o g r a p h y [fig u re ]4 .1 I ) .J Д
h e m a n g io m a , in a d d itio n lo re tin a l d e ta c h m e n t, other c irc u la r zo n e o f h y p o flu o re s c e n c e c o rre s p o n d in g to th e
c a u s e s fo r lo ss o f c e n tra l v i s i o n in Lhese p a tie n ts in c lu d e p e r i p h e r a l p a r t o f t h e h e m a n g i o m a is o f t e n p r e s e n t d u r i n g
c y s lo id m a c u la r e d e m a , la m e lla r m a c u la r h o le fo r m a t io n , t h e e a r l y a n d m i d d l e s l a g e s o f a n g i o g r a p h y . En s o m e c a s e s
a n d e p i re tin a l m e m b r a n e c h a n g e s . C h o r o i d a l n e o v a s c u la r ­ th is c o r r e s p o n d s w i t h a n a re a se e n o p h t h a l m o s c o p i c a l l y i n
i z a t i o n is a n u n c o m m o n c o m p l i c a t i o n i n t h e s e p a t i e n t s . 1 "■ th e s e l u m o r s th a t m a y suggest s lig h t p ig m e n ta tio n o f th e
Th<} m a in te n a n c e o f a h ig h oxygen te n s io n in th e vic in ­ p e rip h e ra l p o r t io n o f th e l u m o r . The re a s o n s f o r th is c o l o r
ity o f th e h e m a n g io m a s m a y be p a rt o f th e e x p la n a tio n , a n d a n g io g r a p h ic c h a n g e are u n c le a r. T v id e n c e o f c y s lo id
i f i s c h e m i a is E m p o r t H i n L i n t h e p a t h o g e n e s i s o f c h o r o i d a l m a c u la r e d e m a m a y be p re se n L re m o te fr o m th e area o f
n e o v a s c u la riza tio n . R e tin a l and o p tic d isc n e o v a s c u la r­ lh e tu m o r . In p a tie n ts w ith c h o ro id a l h e m a n g io m a s w it h ­
iza tio n o c c a s io n a lly d e v e lo p s in p a tie n ts w ilh c h o ro id a l o u t e x te n s iv e s e c o n d a ry d e g e n e r a tiv e c h a n g e s in t h e o v e r ­
h e m a n g io m a s ’ Tw o p a tie n ts p re se n te d to lh e Kascom ly in g R PE and re tin a , a n g io g ra p h y m ay rtve a l only an
P a Jm fir L y e J n s l i t u t e b e c a u s e o f m b e o s i s i r i d is a n d lo n g ­ e x a g g e ra te d b a c k g r o u n d c h o r o i d a l flu o r e s c e n c e in t h e a re a
s ta n d in g b u llo u s re lin a l d e t a c h Ln e n l c a u s e d b y p r e v io u s ly o f L h e t u m o r d u r i n g l h e first f e w m in u te s o f th e s tu d y a n d
u n r e c o g n ize d s o lita ry c h o ro id a l h e m a n g io m a s . n o a b n o r m a l i t i e s d u r i n g th e la te r stages o f a n g i o g r a p h y .
 I n d o c y a n i n e a n g i o g r a p h y re ve als a d ia g n o s t ic p a lte r]! o f F4. E7 Circ umscr ibe d ch oro idal he m angio ma.
e a rly d iffu s e h y p e rflu o re s c e n c e ( w it h in ] m i n u l e ) w i l h late
A —D : A 42-year-old w om an presented w ilh reduted vision
h y p o flu o re s c e n c e (5 m in u te s ) and d e la y e d w a s h o u t p h e ­ f2CV40'i. Fundus дррелглпее ol an oriarye-mloned t/areunv
n o m e n o n (b e yo n d 10 m in u te s ) d u e to e xit o f th e d y e fr o m stxibed Lumor suj^eslivi! ol hemangioma IA ) . Indocyanine
t h e t u m o r ( E ' i g u r e 1 4 . 1 7 ) . 1,10 ajigitrgraphry repeals л di agnostic bsfiern of ijaHy diffuse
l i is l o p a l h o lo g ic a lly a cavernous h e m a n g io m a of lh e hyperfluorescenoe al 1 minute w ith C r delayed w ash­
c h o r o i d is c o m p o s e d o f p r e d o m i n a n t l y h u g e , d i l a t e d , t h i n -
out phenomenon '12 minuCesl. Usin^ slandjard full-
Пиепсе prutotol i ГАГ study} a 6-mm single spol ol" LTealmtml
w a l l e d ve sse ls w i t h m in im a l s tro m a . T h e s e tu m o rs b le n d
was nppli:ed 1.Б]. Six weeks ЗдЕег, nole flattening ol Lhe cjhoroi:-
a lm o s t im p e rc e p tib ly in to lh e s u rro u n d in g norm al cho­
dal кгпкн w ilh m inim al Dverlvinf’ retinal pigmenl epilheliLim
r o i d a l tis s u e ( f i g u r e 1 4 . 1 6 G atid H Ljl h x t e n s i v e c y s tic
nllwalion :Di.
d e g e n e r a t i o n oJ" l h e o v e r l y i n g r e t i n a is u s u a l l y p r e s e n t a n d
En s o m e cases m a y be a s s o c ia te d w ilh e xte n s ive fib ro u s
m e t a p l a s i a o f th e № Ё a n d , less o f t e n , ( t P £ h y p e r p l a s i a .
A lth o u g h not p a th o g n o m o n ic fo r cavernous hem an­ l*e e x p e c t e d o v e r t h e l o n g te rm fo llo w in g p h o lo d y n a m ic
g io m a o f lh e c h o ro id , th e e a rly p a lte rn o f flu o re sc e n c e t h e r a p y . Uiil J l is p r e f e r a b l e l o u s e a s i n g j e t a r g e s p o t r a t h e r
c a u s e d b y th e la rg e v a s c u la r s p a c e s in l h e t u m o r a n d lh e th a n m u l t ip l e o v e r l a p p i n g s p o ts to a v o i d d a m a g e to o v e r ­
la te p a t t e r n o f d y e s t a i n i n g c a u s e d b y t h e cystic d e g e n e r a ­ l y i n g K P f l b a l m a y l e a d t o d e l a y e d v i s u a l l o s s . 1-17
t io n o f th e o v e r ly in g re tin a are i n fr e q u e n t ly f o u n d in a s s o ­ T ra n s s c le ra E cryopexy, m ic ro w a v e ih e rm o th e ra p y , and
c ia tio n w ith o lh e r s im ila rly s ize d tu m o rs . T h e E u p ta k e e xte rn a l-b e a m and e p isc le ra l irra d ia tio n have been used
is u s u a l l y , b u l n o t a lw a y s , n e g a tiv e in c a v e r n o u s h e m a n ­ lo tre at c h o r o id a l h e m a n g i o m a s .]1Пг149-151 B e c a u s e o f t h e
g io m a . "NJ U ltra s o n o g ra p h y g ive s a c h a ra c te ris tic p a l­ m o rb id ity a s s o c ia te d w ith th es e la tte r te c h n iq u e s th ey
t e r n o f h i g h r e f l e c l i v i t y t h a l is h e l p f u l i n d i f f e r e n t i a t i n g a s h o u ld be reserved fo r use e ith e r in th ose p a tie n ls fo r
c h o ro id a l h e m a n g io m a fr o m a m e la n o m a (fig u re 1 4 .1 .6 Ё w hom p h o lo c o a g u la lio n o r p h o lo d y n a m ic t h e r a p y is n o l
and h ) . 1’ ' In th e Ia i t a n a lys is , how ever, th e re d d is h - su c c e ss fu l o r fo r p a lie n t s in w hom , because o f th e larg e
o ra n g e c o lo r o f c h o ro id a l h e m a n g io m a s te v ie w e d w ilh а s ize a n d c e n tra l lo c a tio n o f lh e t u m o r , p h o lo c o a g u la lio n
b in o c u la r in d ire c t o p h t h a lm o s c o p e it th e m o s l im p o r t a n l is u n l i k e l y t o b e s u c c e s s f u l i n r e s t o r i n g o r p r e s e r v i n g v i s u a l
d ia g n o s tic s ig n ( h a l d iffe re n tia te s c h o r o id a l h e m a n g io m a s f u n c t i o n . T r e a t m e n t is o p t i o n a l i n p a tie n ls w i l h th e in c i­
fro m w h ile o r c re a m -c o lo re d m e ta s ta tic c a rc in o m a s and d e n ta l fin d in g of cavernous h e m a n g io m a u n a s s o ria le d
a m e la n o tic m e la n o m a s . O lh e r o ra n g e fu n d u s tu m o rs th a t w ith re tin a l d e la c h m e n l o r e vid e n c e o f p re v io u s d e la c h -
m ust be c o n s id e re d in th e d iffe re n tia l d ia g n o s is in c lu d e m e n l. These p a tie n ls , how ever, s h o u ld be c a u tio n e d lo
serous or p a rtly o rg a n ize d d e ta c h m e n t o f lh e R E ’ E: ( s e e m o n i t o r th e ir v is u a l a c u ity fr e q u e n tly a n d to b e e x a m in e d
fig u re 3.2] a n d 3 .2 3 ) , o s le o m a o f th e c h o ro id (see N g u r e at y e a rly in te rva ls . T r e a t m e n t o f p a tie n ts w ith lo c a lize d
14 . 2 1 A } r n o d u l a r sc le rilis (see fig u re 1L35A), and exo­ d e ta c h m e n t and e vid e n c e o f severe p e rm an e nt m a c u la r
p h y tic re tin a l c a p illa r y h e m a n g i o m a (se e f i g u r e 1 3 . 1 3 ) . dam age is o p t i o n a l . E’ h o l o c o a g u l a t i o n m ig h t be c o n s id ­
fo c a lize d cavernous h e m a n g io m a s o f th e c h o ro id e re d t o p r e v e n t fu r t h e r s p re a d o f re Lin a l d a m a g e c a u s e d b y
lo ca te d in th e e x l r a f o v e a l area a n d a s s o c ia te d w i t h s e r o u s fu rth e r e x te n s io n o f th e re tin a l d e la c h m e n l.
d e t a c h m e n t o f th e re lin a m a y h e tre a te d s u c c e s s fu lly w ith lh e onset o f s y m p to m s in p a tie n ts w i t h h e m a n g io m a s
xenon or in te n s e argon p h o lo c o a g u la lio n d ire c te d lo u s u a l l y is u n r e l a t e d t o a n y r e c o g n i z e d p r e c i p i t a t i n g c a u s e ,
lhat p o rtio n o f lh e tu m o r s u rfa c e w h ere th e flu o re s c e in 'lh e firs l m a n if e s t a t i o n , h o w e v e r , o f a c h o r o i d a l hem an­
a n g io g ra p h y shows e v id e n c e o f d iffu s io n o f dye fro m g i o m a , as w e l l a s c h o r o i d a l o s t e o m a o r a l a r g e c h o r o i d a l
th e su rfa c e o f lh e tu m o r (fig u re ] 4 .1 S LJ; see p . 1 2 Q 6). m e la n o c y lic nevus, in ay be v is u a l lo ss c a u s e d b y d e v e l­
P h o lo c o a g u la lio n s h o u ld be s u ffic ie n tly in te n s e lo cre­ o p m e n t o f s e ro u s re tin a l d e t a c h m e n t in th e m a c u la d u r ­
a te p ro m in e n t w h ite n in g of th e o u te r re lin a ! la ye rs . It i n g t h e Ia l t e r h a l f o f p r e g n a n c y . T h e a u t h o r h a s s e e n i h i s
is s u c c e s s f u l i n c o l l a p s i n g L h e c y s L i c r e l i n a o n lo th e s u r ­ o cc u r in fo u r w o m e n , iw o w ith c h o ro id a l h e m a n g io m a s ,
f a c e o f l h e l u m o r a n d c a u s i n g c o m p l e t e r e s o l u t i o n o f n il one each with a c h o ro id a l O s te o m a and la rg e c h o ro i-
s u b r e t i n a t f l u i d i n m o s l c a s e s . El d o e s n o l a l t e r t h e s i z e o f dat n e v u s . E n ih re e p a tie n ls th e d e ta c h m c n l re s o lv e d
lh e t u m o r . P h o l o d y n a m i c th e ra p y o ffe rs th e a d v a n ta g e o f s p o n ta n e o u s ly soon a fte r d e live ry of th e in fa n t, lh e
s e le c tiv e a b la tio n o f th e tu m o rs w h ile s p a rin g th e o v e r­ added h e m o d y n a m ic stress, a n d p e rh a p s o lh e r e n d o c rin e
ly in g r e t in a .1 140 U s in g sta n d a rd fu ll-fu e n c e p ro to c o l c h a n g e s , o c c u rrin g d u r in g p r e g n a n c y are p r o b a b ly r e s p o n ­
(lA l 3s tu d y) w e h a v e b e e n a b le l o a c h ie v e e x c e lle n t l u m o r sib le fo r tra n s ie n t d e c o m p e n s a tio n o f t h e a lie n e d c h o r i o -
response o f m o re th a n W ith a s in g le tre a tm e n t a p p li­ c a p illa ris and RPH o v e rly in g Lhe h a m a rto m a s . A similar
c a tio n (Fig u re I4 .17A , l ) ) . " l: .R e p e a l t r e a l m e n L m ay be d e c o m p e n s a tio n m ay occur d u rin g pregnancy in som e
n e c e s s a r y b u l it is r e c o m m e n d e d l o w a f t f o r a b o u t 6 weeks p a tie n ts w h o d e v e lo p i d i o p a t h i c c e n tra l s e ro u s c h o r io r e ti­
to 3 m o n t h s l o assess fu ll r e s p o n s e b e fo r e e m b a r k in g o n n o p a t h y in th e a b se n c e o f a n y o l h e r c h o r o id a l a b n o r m a l ­
a d d itio n a l tr e a tm e n t. O v e r a ll, e xc e lle n t v is u a l re s u lts c a n ity ( s e e p . 8 2 ) .
 O t h e r le ss c o m m o n and rare c h o r o id a l tu m o r s o f vas­ 14. f 3 S t u r g e - W e b e r s y n d r o m e .
c u la r o rig in In c lu d e c a p illa ry a n g io m a s (se e fo llo w in g
A and fl: Right and lell eyes. respectively, of a child with lhe?
d escuss i o n } , h e m a n g i o e n d o t h e l i o m a s , h e m a n g i o e n d o l h e - Slurge-VVeEier syndrome wilh nevus ilsmireus involving Lhe
Eio s a rc o m a s , le io m y o m a s , a n d h e m a n g io p e r ic y to m a s .1 : ' left side of [he f a c e and diffuse choroidal vascular hypertro­
phy of Lhe right eye. lhu lifge choroidal vessels in lhe nor­
mal fundus ol lhe left eye were easily seen. The righl iundus
St urge-Weber Syndrome appeared diffusely red, and no vascular details of the cho­
S tu rg e -W e b e r s y n d Fo m e is a n o n f a m i l i a l b a m a r t o m a l o u s roid were visible.
С —H : L o c a liz e d c h o r o id a l h e m a n g io m a in a 9 -y e a r-o td b o y
d is e a s e c h a ra c te rize d by ip sila le ra E a n g io m a to u s m a l­
w ith nevus, fla m m e u s o f [he rig h t side o f hfs fa c e ( C f . H e
fo rm a tio n in v o lv in g lh e b ra in , fa c e (n e vu s fla m m e u s ),
was in itia lly e x a m in e d л I age 7 , a I w h ic h tim e vis u a l a c u ­
and uveal tra c t in a p a t ie n t w h o o fte n h as se izu re s , e v i­ ity in the right e ye w a s 2 0 / 4 0 a n d in the left e y e w a s 20 /20 .
dence o f in Lra c ra n ia l c a lc ific a tio n , and ip s ila te ra l d e ve l­ H is lo ca l o p h th a lm o lo g is t n o te d n o a b n o r m a lity at Lhal lim e .
o p m e n t o f g la u c o m a [ E - 'i g u r e 1 4 .1 8 ) . M o s t p a tie n ts h a v e In N o v e m b e r H ) 7 I Lhe v is u a l a c u ily d e c e a s e d fu rth e r H is
d iffu s e h y p e r tr o p h y o f th e c h o r o id , eye, a n d fa c e o n th e local p h y s ic ia n n o te d a m ass in Ih e in fe rio r fu n d u s for the
s a m e s id e o f th e n e v u s fla m m e u s a n d in tra c ra n ia ] va sc u ­ firs! lim e . t-lis in tra o c u la r pressure w a s n o r m a l, a n d Lherc w a s
no c u p p in g o f Lhe o p lic d iscs. Th e p a lie n l w a s seen in itia lly
l a r m a l f o r m a t i o n . ) j 5 0 L3l N , ' l 5 l -] ^ 155 i n a fe w cases b o t h
a I Ih e K a s c o m K ilm e r E v e In slilu te in Ja n u a ry 1 5 7 2 W ilh a n
eyes m a y b e a f f e c t e d . ]S [ T h e c h o ro id a l h y p e rtro p h y [d if­
a je v a tfid , red dish lu m o r in v o lv in g m o s l o f the in fe rio r ball
fu s e a n g i o m a ) g ive s th e f u n d u s a r e d d is h g l o w co m p ared o f lb e fu n d u s . IL e x te n d e d u p Lo a n d b ise cte d Lhe m a c u la .
to th e o p p o s ite eye [i-'ig u re 1 4 .IS A a rid L ? ) .3 ' " E l e v a t i o n T h e re w a s serous d e ta c h menL o f Ihe retina o v e rly in g the
o f th e in tra o c u la r pre ssure a n d g la u c o m a to u s n ip p in g o f lu m o r e x c e p l in o n e a re a t e m p o r a l Iо the m a c u la w h e re a
th e o p tic d is c m a y b e p re s e n t. S o m e p a tie n ls w i t h S tu r g e - 4 X fj d is c d ia m e Le r, o v a l, g r a y -w h ite e x u d a tiv e m e m Eira n e
W eber syn drom e h a v e a fo c a l area o f a n g io m a t o u s th ic k ­ was present Eie tw e e n lh e tu m o r a n d o v e rly in g re tin a . The
relinal d e ta c h m en I d id n o t texLend inlo Ih e s u p e rio r fu n d u s *
e n in g o f th e c h o ro id in a d d i t i o n to th e d iffu s e t h ic k e n in g
T h e p a lie n l w a s lost Lo fo llo w -u p until M a r c h 1 ^ 7 3 , w h e n he
[ E - 'i g u r e 1 4 .1 Й С - Н } . En t h e a u L h o r ' s e x p e r i e n c e i t is t h e s e
re lu m e d w ilh o n lv Ii i^h-l p e n .e p lio n in Ihe rig h l e y e . A l I hat
p a lie n ts w h o are m o s t lik e ly i o d e v e lo p s e c o n d a r y re tin a l
L i m e h e h a d a l o t a I b u llo u s d e la c h m e n l o f the relin a e x c e p t
d e ta c h m e n t w ith s h iftin g o f th e s u b re tin a l flu id , e ith e r in Ih e area o f g r a y -w h ile s u b rt'tm a l m e m b r a n e !in d ic a te d
s p o n ta n e o u s ly o r a fle r filte rin g o p e r a tio n s fo r g la u c o m a , in b l a c k in lb e fu n d u s d r a w in g a rro w , D , . i n d b y arrow 's in
in m ost cases th e lo c a lize d h ig h ly e le v a te d p o rtio n of E !. T h e lu m o r (s lip p le d area in fu n d u s d r a w in g . 13) w a s
th e tu m o r is lo c a te d so m ew h ere in th e p o s te rio r fu n ­ u n c h a n g e d . TEie relina! p ig m e n l e p i I h e liu m itif3E^ a p p e a re d
Lo b e n o rm a ] e ls e w h e re o v e r Ihe surface o f th e Lu m or.
d u s in ih e p a r a m a c u la r area, lh e re tin a r w h ic h is u s u a l l y
Flu o re s c e in a n g io g ra p h y re v e a le d dr M u s i on o f d y e fro m Lhe
a tta c h e d lo th e d o m e o f th is lo c a lize d th ic k e n in g , s h o w s
surface o f lh e lu m o r in lo lh e g r a y -w h ile s u b re lin a l m e m ­
m a r k e d cy& lic d e g e n e r a t i o n a n d s o m e y e llo w is h a n d gray b ra n e te m p o ra l lo t h E m a c u la (F ). T h e r e w a s n o e v id e n c e o f
tis s u e ly in g b e tw e e n Lhe re lin a and ih e tu m o r su rfa c e . a b n o rm a l c h o r o id a l flu o re s c e n c e e ls e w h e re . H e a v y x e n o n
A n g io g ra p h ic a lly , Lh is area in th e fu n d u s is u s u a lly th e p h o to c o a g u la tio n w a s used lo I real the are a o f the s u b re lin a l
o n ly o n e t h a t s h o w s e v i d e n c e o f s t a i n i n g . En t e n s e x e n o n m e m Eira n e i C ) . In M a y 1 4 7 3 Lhe re lin a w a s c o m p le le k ftat
o r a rg o n p h o to c o a g u la tio n to lh is area m a y b e su c c e s s fu l a n d Lhe vis u a l a c u ily h a d re lu m e d Lo 2 0 / 4 0 0 (M . S o le the
faint Iгас Iio n lines ra d ia tin g I h ro u g h th e cenlral m acuilar area
in re a tL a d lin g ih e re lin a [K ig u re 1 4 .I S C - 11). Jle tin a l a n d
Ia rro w ) to w a rd lh e area o f p h o lo c o a g u la tio n Im rp o ra l lo Lhe
c ilio c h o ro id a t d e ta c h m e n l o c c u rrin g im m e d ia te ly a fle r
m a c u la . R E , righl e v e .
filte rin g su rgery m ay re a tta c h w ith o u l Lre a lm e n L. W hen
e le v a lio n o f th e h e m a n g i o m a is s o a b r u p l l h a l a d e q u a t e
tre a tm e n t c a n n o t h e a p p lie d b y th e ira n s p u p illa ry ro u te ,
in tra v itre a l p h o to c o a g u ia tio n m ay prove su c c e s s fu l. En d e ta c h m e n t Es probably u nnecessary. S c a tte r tre a u n e n l.
th e a b se n c e o f e v id e n c e o f a lo c a liz e d c h o r o id a l tu m e fa c ­ how ever, m ay p rove lo b e u s e fu l i n p re v e n tin g re cu rre n t
tio n o r p ig m e n ta r y re lin a l d e g e n e ra tiv e changes, th e use d e ta c h m e n t in p a tie n ts afteF s u c c e ss fu l r e a lla e h m e n l o f ih e
o f p r o p h y l a c t i c s c a tte r la s e r t r e a t m e n t to prevent re tin a l re tin a .
 A t th e Flu o re s c e in C lu b M e e tjfig in 1990, Dr. M t> rLt>n F 4 .E 8 C o n tin u e d

G o ld b e rg r e p o r t e d a p a t i e n l w h o , a f t e r p r o p h y l a c t i c sc a l-
I: i k u l ] гоел Й ел О Д гзП Й р л Iiс>-лI with Slufjje-W ^ber s yn ­
te r l a s e r L r e a l m e n t i n lh e m a c u la d o n e Lo p r e v e n t r e tin a l d ro m e showing lhe typical r a fird a tM ra iJt c-aici fica I i on af lhe
d e ta c h m e n t b e fo re л g la u c o m a filte rin g o p e r a tio n , d e v e l­ va s c u la r йЛаЧйаЕу a f th e b ra in .
oped lo ss o f c e n tra l v is io n caused b y c h o ro id a l neovas­ |-L: This- £ -year-old th ild , w ilh (inly slighL «densldfl o f lhe
c u la riza tio n o c c u rrin g al lh e s ite o f a p h o to e o a g u la lio n righl facial dngioma lo her left IS te Ll)f deiftlaped b ilatent
scar. P h o lo d yn a m tc th erap y has a ls o been Irie d b u l can relinal detachment asiocialed with m issive thickening of
Iho .h f.il I r.scl in : iih eve--. 1'ii- lliit kon vl, v.'.k i.i: i n. ir
cause tra n s ie n t xvo rs e n in g o f e x u d a tiv e re lin a l d e ta d i-
lhe rii^hl eye and 8m m in Lhe lefl eye ultraiitftOfpaphlcally
m e n t . ' ' ' r ''■ ',fl U s e o f lo w -d o s e e xte rn a l-b e a m irra d ia tio n
fK and l.j. It was n(rt possible angiographically lo define
20G y in m u ltip le fra c tio n a l doses has p roved success­
the sites erf R PE decompensation. The patient undfrwrml
fu l in c a u s in g re tin a l re a tta c h m e n I w i t h in f> -12 m o n lh s UKterml-irearn i*md ial ion using nfaCtidilaf tksagES for a Lola I
in p a lie n ti w ith 5 tu r g e - W e b e r s y n d r o m e .1 " ' 1,1 " T h is ol 1800 c C y to each eye. There was prompl Fesoiulicn ol lhe
t r e a t m e n t was u s e d s u c c e s s fu lly in th e c h ild illu s tr a te d in subretinal fluid rind reduction in Ihe choroidai 1hickness.
1 'tg u re 1 4 .IS (J-K J lo cause re s o lu tio n o f b u llo u s re tin a l
N in e months la Lei her visual acuity was 20/? DO right eye and
2Q/4D left eye.
d e t a c h m e n t o v e r ly in g m a s s iv e d iffu s e u v e a l h e m a n g io m a s .
f o r m e fr u s te о Г S t u r g e - W e b e r s y n d r o m e m a y o c c u r , e .g ., iA a n d H . f r o n t h-Lif-.ic !■[ o l. ■' О I 4 7 J . A n in in L iin M c c h L .ii А я и ч ia L iu n . A l l
n^jhi I». m ew ed.
a c h i l d w i t h a n ip s ila te ra l s o liLa ry c h o r o i d a l h e m a n g i o m a
and fa c ial a n g io m a w i t h o u t d iffu s e ch o ro td -a l a n g io m a ,
s e izu re s , o r e v id e n c e o f in tra c ra n ia l a n g io m a .
Ipsilateral Facial and Diffuse Uveal F 4. '19 Ip si Ia le га! с a pilla ry л n gio in а о f s k i n a n d u ve a l
t r a d a s s o c ia t e d w it h a n e u r y s m a l d ila tio n o f retin a l
Capillary Angioma Associated with a rte rie s, m i c r o p h l h a l m o s , h e t e r o c h r o m ia o f Ih e iris,
Microphthalmos, Heterochromia of the a n d h y p o to n y .

Iris, Chorioretinal Arterial Anastomosis, A : N o l o Ip le v g te d p a r tly in v o l u t e d c u t a n e o u s h a m a n o fo m -e o n

and Hypotony lh e fo re h a n d , m lc ro p h th a lrtro s , .m d iris h e t e r o c h r o m i a in th is

o th e rw is e h e a llh y 2 1 -m o n lb -o ld Ш
Dr. Gass h ad seen an (J C ifa n t W ^ tt h i p s i l a t e r a l c a p i l l a r y h e m ­ B : D ila te d iris vessels left a lt o w ) a n d irreg ular a n g io m a to u s
a n g io m a in vo lv in g th e fo r e h e a d , iris, a n d c h o r o i d a s s o c i­ m ass (right a rro w ) e x te n d in g . In to (he a n te rio r-c h a m b e r a n ^ le
a te d W ith m ild m i c r o p h t h a l m o s , h y p o t o n y . d ila te d re tin a l o l 1htf righl e y e .
a rte rie s , r e t i n o c h o r o i d a l a n a s t o m o s i s , and b u llo u s re lin a l
: F-undus d r a w in g o f right e y e . N o t e d ila le d to rtu o u s relinal
arteries tha l a p p e a re d lo e x it lb e e ye in Lhe p e rip h e ra l zo n e s
d e ta c h m e n t (Fig u re 14 I 1) ) . T h e r e was no h i s t o r y o f se i­
ot c h o ro id a l a tro p h y .
zu re s ; c o m p u te d to m o g r a p h y o f th e b ra in and her general
D-F: B u llo u s re lin a l d e ta c h m e n t a n d d ila Le d to rtu o u s
m e d ic a l e va lu a tio n s w ere n o rm a l. At lh e tim e o f in itia l s u p e ro le m p o ra l reLinal a rte ry l a r r o w il.
e xa m in a tio n u n d e r general a n e sth e sia al 6 w e e k s o f a g e .. G : H -s c a n and H , А -s c a n иКгд вопйцд нрЕту s h o w in g rrtlin a l
Lhe lo c a l re tin a l s p e c ia lis t n o te d to rtu o u s d ila te d re tin a l d e la c h m e n l a n d h ig h ly re fle c tiv e d iffu s e c h o r o id a l m a s s .

arteries e x t e n d i n g f r o m l h e o p t i c d i s c s u p e r i o r l y Lo s e v e r a l I and ): PhcEcxnicnogfapliS of right showing ciosed

Earge w h i l e a tro p h ic areas, w h ere Lhey a p p e a re d e ith e r lo anterior chamber, calciliori lens, fun nol-shaped retinal
rielachmenl, and didfusE; п М Ш FiSrnaftffloim ot" the cho­
a n a s to m o s e w i t h th e c h o r o id a l c irc u la tio n o r to e xit fr o m
roid !arrows. I- High-power view :J■shows details of capil­
th e eye. 'Jh e r e W as n o e v id e n c e o f re lin a l d e t a c h m e n t . T h e
lary hemangioma. Note Ihe Mroma separating the capillary
re tin a appeared ih ic k e n e d , b u t no e vid e n c e o f a d iffu s e channels.
c h o ro id a l a n g io m a Was n o le d . The in tra o c u la r pressure
m easu red 1 -2 m m Mg. Several m o n th s Eater lh e p a tie n t
d e v e lo p e d e vid e n c e of a n in fe r io r re tin a l d e ta c h m e n t a n d
a d iffu s e re d d ish c o lo r of th e f u n d u s s u g g e s tin g a d iffu s e
c h o ro id a l a n g io m a . A l il m o n th s , e x a m in a tio n by th e
a u th o r c o n firm e d th e p re v io u s o b s e rv a tio n s in a d d itio n l h e r e tin a l d e t a c h m e n t w a s u n r e s p o n s i v e to ira n s s c le ra l
to a to ta l b u tlo u s re tin a l d e tach m e in except in th e areas c r y o p e x y o f Lhe areas o f s t a in in g b u t w a s p a r tly r e s p o n s iv e
o f p e rip h e ra l c h o rio re tin a l a tro p h y s u p e rio rly (Fig u re t o scle ra l w i n d o w s done in th e th ic k e n e d scle ra in each
1 4 .l y C - F ) . T h e re w as n o e v id e n c e o f a re tin a l h o le , and q u a d ra n l. S e ve ra l y e a rs la te r Lh e p a l i e n t lo s l lig h t p e r c e p ­
no e x p la n a tio n fo r lh e h yp o to n y. 3"he a n g io m a on lh e t i o n , b u t s h e r e t a i n e d t h e e y e u n t i l a g e S y e a r s w h e n it w a s
fo re h e a d show ed e vid e n c e of som e re g re ss io n (Fig u re e n u c le a le d . lh e v is u a l a c u ity in liie norm al le fL e y e w a s
1 4 .1УA ). W h e n th e p a tie n t c rie d th e re w as e v id e n c e o f a 2Gy 20-
s u b c u ta n e o u s a rte rio v e n o u s m a lfo r m a tio n a d ja c e n t to th e G ross and m ic ro s c o p ic e x a m in a t i o n of th e rig h t eye
p o s te rio r edge o f th e c u ta n e o u s a n g io m a . A n g io g ra p h y re ve a le d a m ic ro p h th a lm ic eye w ith a d iffu s e c a p illa ry
co n fin n e d th e a rte ria l n a lu r e o f th e d ila te d r e lin a l ve sse ls h e m a n g io m a of th e c h o ro id excepl in lh e p e rip h e ra l
and show ed s l a i n in g p rim a rily c o n fin e d to th e p e rip h ­ /o n e s o f c h o rio re Lin a ! a tte n u a tio n (Fig u re I4 .1 9 E and ]).
eral zo n es o f c h o rio re tin a l a tro p h y (Fig u re I4 .1 9 E -') . E x t e n s i v e a t r o p h y o f t h e iris a n d c ilia ry b o d y , a ru p tu r e d
U ltra s o u n d re ve a le d d iffu s e t h ic k e n in g o f th e c h o r o id by c a lc ifie d c a ta r a c lo u s le n s , a n d a f u n n e l - s h a p e d d e t a c h m e n l
a h ig h ly re fle c tiv e tu m o r, whose average e le v a tio n was o f Lhe d e g e n e ra te d r e tin a w e r e p re s e n t. T h e r e w e re n u m e r ­
a p p ro x im a te ly 4 m m (Fig u re 1 4 .3 У С and H ), as w e lE as ous Large c ilia r y a rte rie s a n d v e n o u s c h a n n e ls in th e e p i ­
d i l a t e d o r b i t a l b l o o d ve sse ls in th e r ig h t o r b i l . scle ra l t is s u e s u r r o u n d i n g l h e o p l i c n e r v e .
 T h is p a tie n l. u n lik e p a L i e n Is W i t h S tu rg e -W e b e r syn­ 1 4. C h o ro id a I o s te o m a .

drom e, had o c u lo c u ta n e o u s c a p illa ry ra th e r lh a n cav­

A a n d B : C h o r o i d a l o s l e o m a in а 2 5 - y e a r - o l d w o m a n c o m ­
e rn ous h e m a n g io m a , m ic ro p h th a lm o s ra th e r th a n lh e p la in in g o f b lu rre d v is io n . There w a b л v iT tu m s c r ib e d o ra n g e
o c u la r h y p e rtro p h y th a t fre q u e n tly a c c o m p a n ie s S tu rg e - su E>netinal mi^ss ir [h e m a c u la w ilh m in im a l charri’ e s in
W eber syn dro m e , and h yp o to n y ra th e r th a n g la u c o m a . th e o ve rlyin g re tin a l p ig m e n t e p ith e liu m (R P E ) lA j. O v e r
U n lik e p a tie n ts w ith S tu rg e -W e b e r s y n d ro m e a n d re tin a l а 2 -y e a г p e rio d th ere p r O g r t e s i V-ё d e p i g m e n t a l i o n ol
L h e К P E o v 4 i r l y i n ^ t h e l u m o r H K :. V i s u a l a c u ity w a s 2 0 /2 0 .
d e ta c h m e n t, th e re w a s no fo c a l e le v a tio n o f th e d iffu s e
U ltra s o n o g ra p h y and co m p u ted to m o g ra p hy re ve a le d e vi­
a n g io m a or a w e ll-d e fin e d area o f ftM S d e c o m p e n s a tio n
dence? ot a ch o ro id a l osLeom a. Over Lhe subsequent
a n g io g ra p h ic a lly th a t w o u ld p e rm it us to d ire c t e ith e r
y e a n o f f o l l o w - u p Lhe t u m o r e n la r g e d slFgbLly a n d s u b r e lin a l
p h o to c o a g u la tio n o r c ryo th e ra p y. Because o f th e m ic r o p h ­ f i b r o v a s c u l a r p r o l i f e r a t i o n w a s a s s o c i a t e d w i l h a d e c r e a s e in
t h a l m o s a n d t h e t h ic k e n e d s c le ra , w e e le c te d to tr y s c le ra l v i s u a l a a i l | j ( Lo 7 / 4 0 ( 5 .
W in d o w s d e sp ite th e absence o f u ltra s o n ic e vid e n c e o f С a n d D : A 1 0 -y e a r -o ld ^irl p jo s e n Le d w i lh acu te loss o f
uveal e ffu s io n (c ilio c h o ro id a l d e ta c h m e n t). lh is W as vis io n in the rifjht e ye c a u s e d b y a s u h fo v e a l ty p e II c h o r o i­
p a r tly s u c c e s s fu l. A l t h o u g h we knew l h a l fa c ia l h e m a n g i ­
dal n e o vn rc и Iа г iza Li o n a n d h e m o rrh a g e o v $ d y fh jj a Загце
m a c u la r a n d ju x la p a p illa ry c h tw o id a l osLeom a in lh e ri^hl
o m a w a s a ty p ic a l c a p illa ry a n g io m a , w e d id n o t c o n s id e r
e v e . Shu bad A ce n tra l d iscifa rtri hl at o v e rly in g a s im ila r o s te ­
Lh e p o s s ib ilit y th a t t h e u v e a l a n g i o m a m i g h t a ls o b e a c a p ­
o m a in I ho lefL e y e . Th e b lo o d re s o lve d in Lhe ri^hl e y e a n d
illa ry a n g io m a . W iLs c h e l a n d K o n t* in a re vie w o f t h e h is - she re g ain e d 2 0 /3 0 vis u a l a c u ily , w h ic h s h e re ta in e d u n lil
to p a th o lo g y o f 4 5 s o lita ry a n d 1 7 d iffu s e h e m a n g io m a s o f age 2 4 y e a rs . D u r in g Lbat fo llo w -u p p e r io d Lbe d ia m e te r o f
th e c h o r o id , f o u n d th re e cases o f s o lita ry a n d n o cases o f Lhe o s te o m a in lioLh e y e s inc r e n t 'd n li^ h llv a n d I h ere w a s
d iffu s e c a p illa ry a n g io m a s : N a id o ff el a l.1" a n d Itu ltu m C K tensive depi ^ m o n La Lio n o f the K P E o v e rly in g lh e o s te o ­
e t a l . " ' ' r e p o r t e d iris a n g i o m a s a s s o c i a t e d w i t h c u ta n e o u s
m as IГЗ>. M o te lh e vascLrbir Lrunks la rro w s , D j o n Lbe Lu m o r
ни nface.
p e r io r b ita l c a p illa r y a n g io m a s , tn o n e case th is w a s a s s o ­
E—1: G r o w t h o f a p e rip a p illa ry c h o ro id a l o s te o m a o v e r a
c ia te d w ith d iffu s e c o n g e n ita l a n g io m a to s is .1 I f fa c e d
5 -y e a r p e rio d in a 1 3 -y e a r -o ld m a n ' L nnrl F:-. A fro n ta l-v ie w
w i t h a n o t h e r s im ita r case, th e a u t h o r w o u l d c o n s id e r th e
ro e n tg e n О ф в гП o f left e y e sbfaw n irt ^ rep ea led p c rio p Lic
use o f in te r fe r o n -a lp h a ., w h ic h has been e ffe c tive in th e c a lc ific a tio n (a rro w . C l . R ig h t e v e o f s a m e p a tie n l s h o w in g
t r e a t m e n t o f s o m e cases o f s y s te m ic c a p illa r y a n g i o m a t o ­ d e v e lo p m e n t o f a n o s te o m a a n d th o r o id a l n e o v a s c u .a r i^ a -
sis. A n o t h e r o p t i o n l h a l s h o u l d b e c o n s i d e r e d is e x t e r n a l - Мол i.nrrow , Ii in lh e in itia lly. un in v o lv e d e v e IЬЧ:.
h e a m irra d ia tio n .
[—1 : T h is 2 9 -y e a r-o ld w o m a n w i ib a c h o r o id a l o s te o m a
d e v e lo fK 'd vis u a l b lu rrin g in the ri^ h l e ye d u rin g Lhe East tri­
Som e in te re s tin g and unansw ered q u e s tio n s in th is
m ester o f p re g n a n c y ■!I . N o te the s p o n la n e o u s rapid re s o lu ­
c a se are: W h a t w a s t h e c a u s e o f t h e h y p o t o n y th at w as a
tion o f s u b ie lin a l e x u d a tio n lh al o c c u rre d w ilh in several
c o n s is te n t fin d in g on every e x a m in a tio n , even p rio r Lo n o n L h s a fte r d e liv e ry : К th re e years later she is a syrn p to m .-
Lhe d e v e lo p m e n t o f re tin a l d e ta c h m e n t? H o w d i d i! re la te a Li с. 1 h e o s te o m a is largei IL I.
to th e apparent re tin o c h o ro id a l and re tro -o rb ita l a rte ­
I A .i ih :; Ц . I m n ; (.■::* Г л г i ; i r, i J W i l k i r i M J i r ' ' ' , |11: 1, i. ■11 w i l h ^гптпам гнп Г т г п
ria l a n a s to m o s is ? W a s h y p o t o n y i m p o r t a n t i n c a u s in g th e i hi: A m fcd tan luu m .il оГ C 11■
I ; I ,. I.■i i 1 1 n jp v ■i-;lr b y Г Ь * Ljf^ilM .ilm iL

m ic ro p h th a lm o s Г W h y d id th e re tin a l s p e c ia lis t, w hose

ГиЫпМипн tJu. (. .milI LJ. Inim Gjbs c;L .lI s I) IV7B, Amuric.Ln V iLd k .il
A u c K i x l t M . ' A f t r uhlb n ' l i T w d Ь- l . Г т п ; Li.ibs.' '
p r e s u m p tiv e d ia g n o s is w a s a v a ria n t o f S tu r g e -W e b e r s y n ­
d r o m e , n o l fin d e v id e n c e o f a d iffu s e c h o r o id a l a n g io m a
at t h e t i m e o f h is in it ia l e x a m i n a t i o n at 6 w e e k s o f ag e? 1 - K . . a n d 3 . 7 8 A ) . T h e r e is o f t e n s o m e m o t t l i n g o f g r a y p i g ­
C o u ld th e a n g io m a h a ve d e v e lo p e d o r e n la rg e d d u r in g th e m enl on th e t u m o r su rfa c e , lh e o ra n g e c o lo r o f th e J t P E
n e o n ata l p e rio d ? G r o w t h o f c a p illa ry a n g io m a s in s y s te m ic m ay s till b e preserved over th e p e rip h e ra l aspect o f th e
c o n g e n iLa l a n g io m a to s is m ay occur d u rin g th e firs t f e w lu tn o r A d e p e n d e n t z o n e o f E P t a tr o p h y caused b y p rio r
m o n t h s a f t e r b i r t h , 15* lo n g -s ta n d in g re tin a l d e t a c h m e n t m a y be p re s e n t. A c h a r ­
a c te ris tic a n d p a th o g n o m o n ic fe a tu re w h e n v i s i b l e is t h e

C H O R O ID A L O S T E O M A presence o f num erous s m a ll v a s c u la r s p id e rs lo c a te d o n

t h e L u m o r s u rfa c e in areas w h e r e th e p i g m e n t e p i t h e l i u m
C h o r o i d a l o s t e o m a s a ris e in th e ju x f a p a p illa iy a n d m acu­ is d e p ig m e n le d [E 'ig u r e 54 . 2 0 C and L> ). Ih e s e are th e
la r re g io n u s u a lly in y o u n g fe m a le s w h o are seen b e c a u s e fe e d e r b lo o d v e sse ls e x i t i n g fro m th e h o le s in (h e a n te ­
of m e la m o rp h o p s ia and a p o s itive sc o to m a caused by rio r su rfa c e o f th e c a n c e llo u s b o n e . S h ey in te rc o n n e c t th e
e ith e r serous o r h e m o r r h a g i c d e t a c h m e n t o f t h e m a c u la ., m o d ifie d c h o r io c a p ll la ris on th e a n te r io r su rfa c e o f th e
th e la tte r a s s o c ia te d w ith c h o ro id a l n e o v a s c u la riza tio n tu m o r w ilh th e la rg e c h o ro id a l v e sse ls th at lie p o s t e r io r
(Fig u re s 1 4 .2 0 and f 4 . 2 ! A - C ) . lilc,|c,|' '- I:>n in itia lly , th e s e lo lh e t u m o r (F ig u r e 1 4 . 2 1 1 1 ) . i n s o m e ca se s th e s e ve sse ls
tu m o rs , w h ic h are g e n e ra lly o n ly s lig h tly e le va te d , m ay fo rm la rg e v a s c u la r t r u n k s b e n e a t h th e re lin a . C h o r o id a l
a p p e a r o r a n g e in c o lo r a n d m a y s im u la te a c h o r o id a l h e m ­ n e o v a s c u la riza tio n or s u b n rtin a l fib ro u s m e ta p la s ia m ay
a n g io m a [i'ig u r e ( 4 .2 0 A J . U s u a lly how ever, hy Lhe L i m e be e v id e n t (Fig u re s 1 4 .1 0 С and l> , a n d 1 4 . 2 1 A ) , l6 ii-L
th e p a tie n t b e c o m e s s y m p t o m a t ic , d e p ig m e n ta lio n o f th e 'lh e tu m o r m ay b e m u ltic e n tric (Fig u re 1 4 .2 0 E } . It m a y
f t P E has occurred and th e t u m o r has а стеаш c o lo r and b e p re s e n t o r d e v e l o p la te r in th e o p p o s i t e e y e i n a p p r o x ­
w e ll-d e fin e d g e o g ra p h ic borders (fig u re s 1 4 ..2 0 Б -К and im a te ly 10 -2 0 % o f cases (E 'ig u r e 1 4 .2 0 1 1 and E } .:
H u o r e s c e in a n g i o g r a p h y d e m o n s t r a t e s a n irrt'g u la r p a tte r n F4.^1 C h o ro id a l o s te o m a .

o f e a rly h y p c rflu o re s c e n c e in th ose areas w here th e K H i

A —< : This; 1 J5-year-old ^ irl fc x p e rje n c id ra p id Itfts o f cenlral
is t h i n n e d and la te fo c a l s t a i n i n g in (h o se p a tie n ts w ith vis io n in lh<- lull EieCfiuse o f suENeLina] n e crta scu la rln a tio n
s e ro u s d e t a c h m e n t o f th e re tin a w i t h o r w i t h o u t c h o r o id a l i л r o w s I c o m p lic a tin g a I a № c h o ro id a l o s te o m a . N o t e the
n e o v a s c u l a r i z a t i o n . Ele c a u s e o f s lu g g is h b l o o d H o w w i t h i n h y p « p j f f i № n t | i a n o f [ho nErtivastiular m e m b ra he* lhaL p ro b ­
th e o s te o m a , th e a n g io g ra p h ic d e m o n s tr a tio n o f d isc re te , a b ly is a ly p e 2 s u b s e n s o ry retinal m y m b r a n e . i h e had a
e a rly p e r fu s io n o f th e v a s c u la r s p id e rs o n th e t u m o r su r­
iiim iNir o s te o m a in ih e le Elq w ^ y e . Shu has t w o sib lin g s w i lb
b ila te ra l t b d i o i t k l o s te o m a s .
fa c e d o e s n o t o c c u r , in th e la te p h a s e s o f th e a n g i o g r a m ,
i ?: A r r o w s ind rca le o s te o m a in the 9 -y e a M jld m a lu s ib lin g o f
h o W e v e ii t h e y a re o fte n s e e n as n o n flu o re s c e n t s tru c tu re s
ih e p a tie n t Illustrated in A -C .
o n a b a c k g r o u n d o f flu o re s c e in s ta in in g o n th e t u m o r s u r­
E and F: S e v e r a l s m a ll c h o r o id a l o s te o m a s d e v e lo p e d d u r­
fa c e . - S p o n t a n e o u s r e a t t a c h m e n t o f t h e m a c u l a m ay occur in g o b s e r v a t io n of a 1 0 - y e a r - o ld b la c k y id d u r in g n iu llip le
w ith or w ith o u t c h o ro id a l n e o ^ a s c u Ia n i m a t i o n , and th e E p i s o d e s o f B jE a t e r a l o r b i l a l ir F j a r r i t o a t o r y p s u u d o l u m o j a n d

p a tie n t m a y re g a in e x c e lle n t v is u a l a c u ity . (H g u re i 4 .2 ( 4 1 d tr a n s ie n t p e r io d o f m i l d f iy p f t p a r a lh y r i^ ls jr t . She bnd no

e v id e n c e of in t r a o c u la r in flfiin rn H itio rt. C Jo m p u l e d to m o ^ ra -
a n d D ) . 1 ' 1'
p h v d e m o n s l r a l e d 1l i e o s t e o m a f a r r o w , F l d e p i c l e d in L
D r. G ass h a d seen ra p id re s o lu tio n о I a lip id -ric h su b -
G : U l t r a s o n o g r a p h y o l a n o t h e r p a t ie n t w i t h a s i m i l a r ju x t a -
re tin a l e itu d a le caused by c h o ro id a l n e o v a s c u la riza tio n
p a p iR b fy a n d m a c u la r c h o r o id a l o s t e o m a s h o w in g a b s e n c e
o v e r ly in g a ju x t a p a p illa r y c h o r o id a l o s t e o m a in a w o m a n ot e c h o e s p o s t e r io r I о :iic lu in o r (a r r o w s ).
w ith ra p id v is u a l lo ss in th e n in th m o n th o f g esta ­ H : H i s t o p a l b o l o y y o f o s l e o m a o f 1 h e L E m r o id s h o w s p l a g u e
t i o n . ]Q6j 157 D i s a p p e a r a n c e o f t h e e x u d a t i o n and re tu rn o f of c a n c e llo u s Ьолеы ly in g b e lw e e n ih e i n n e r o r t e - lh ir d a n t i

v is io n o c c u r r e d d u r i n g t h e 6 m o n t h s a fte r d e li v e r y ( fig u r e o u le r tw o - th ir d s ot ih e c h o r o id .

M .2 U |- L ) . I’ h o t o c o a g u l a t i o n m ay be in d ic a te d fo r th e I- К : H i I д I e r a I s c i e n o L l i o r o i d a i o s t e o m a s w e r e p r e s e n l in th is
c h i l d w i t h f a c i a l l i n e a r s e b a c e o u s n e v u s o f la d a s s o h n .
tre a tm e n t o f su b re tin a l e xu d a tio n caused by neovascu-
la r m e m b r a n e s th a L a re o u t s i d e t h e c a p i ll a r y - f r e e z o n e . '' IA-1> , fro m N c ib lu .- 1' 1 t . i n J К fro m K . t l j .m d C.i-.iKi-"'1 > I (ja.S A m e Id . lit
M cu I i L l i I A sn < ji:. l1.m ii . ЛИ rig h ts i v iiir v t 'f i. I intd K. Ih Jm Л 1 1 и к :й E l nl '
In tr a v itr e a l b e v a c iiiu m a b c a n a ls o in d u c e re g re s s io n o f th e
ii Irrinri (J.hM c ! .:l " *.'■ ! 97JS. A iu c r u .m iV k d u .il A d ivtiLi.ilio n . A ll ri^ h ti
n e o v a s c u l a r m e m b r a n e . 1 JS ETh o t o d y n a m i c t h e r a p y m a y b e rflirv cd j
p re fe ra b le f o r t h e tre a t m e n t o f e x tra m a c u l a r n e o v a s c u la r
m e m brane [fig u re ] 4 . 2 2 ) . 1 '' In c id e n ta l d c c a lc ific a tio n o f
th e o ste o m a (Fig u re 1 4 . 2 2 E —I ) fo llo w in g p h o lo d y n a m ic
th e ra p y and even la s e r has been r e p o r t e d . 21" '['h e r e is
b e lie f th a t d e c a lc ific a tio n m a y s lo p fu rth e r g ro w th o f th e
o s t e o m a ; h o w e v e r d e c a l с in e a t i o n under th e fo ve a re su lts
in a t r o p h y a n d lo ss o f v i s i o n .
 T h e f u n d o s c o p i c p i c t u r e is u s u a l l y s u f f i c i e n t l y c h a r a c t e r ­ F 4 .2 2 C h o ro r d a I o s ie o m a .

is t ic t o p e r m it a n a cc u rate d ia g n o s is . Ih e d e m o n s tra tio n

A —E: A .‘iO-veaf-old white Wom an presented w ilh a
o f m arked a tte n u a tio n of sound by th e lu m o r u ltra s o - recent-onset blurred vis-ion or 2 weeks' duration ;2fV.3.Cr.
n o g ra p h ie a lly or o f c a lc ific a tio n o f th e t u m o r b y e ith e r Ophthalm oscopic evaluation of Lhe ]eft eye revealed a soli­
o rb ita l r < k n tg o to g fc & p h y o r c o m p u te d e p m o g fe p h y m a y be tary amelanolic с: <Lii lesion rn I fie1 superior m acular
used to c o n firm ih e d ia g n o s is (N g u r e s I 4 .2 0 G a n d 1 4 .2 1 F region. The lesion was aobiti Ъ X .5 mm in ЬлsaI dimension
and с ] _ 1£6. ] 7 5 г Ь б j ^ a g n e |1[c r e s o n a n c e i m a g i n g s h o w s le ss and w as m inim ally elevated. The margins were s*:alloped.
O verlying retinal hemorrhages and иubrtrtinaI fluid, w hich
s p e c ific f i n d i n g s .| J
extended into the fovea I region, were л I so observed [A).
I lis to p a th o lo g ic a lly th e s e tu m o rs are com posed of
К -scan ulLrasLinu^riifihy demons’ rak'd hjgh refleeiivitv a1 the
p la q u e s or m ounds o f ел n e e l i o n s bane th a t l ie b e t w e e n
Fevet of Ihe choroid suggestive of-calcium deposition. O n flu­
th e a lte re d e h o r i o c a p i H a ris and th e o u te r c h o ro id a l cir­ orescein angiography, Iho lesion m vealed earlv palchy byper-
c u la tio n (fig u re 1 4 .2 1 1 ]} . Ih e la rg e c h o r o i d a l b l o o d ves­ lluorescence and late staining :R:. In addilion, overlying
s e ls c o m m u n i c a t e th ro u g h th e c a n a ls w i t h i n th e b o n e to the posterior aspect o f the choroidal lesion, lacy hyperfluo-
e h o r i o c a p i l l a r i s . ' ' 10 ,I ( ' - T h e R F E o v e r ly in g th e s e t u m o r s
rescenoe inditalivE^ of extratoveal classic chftmfdal neovas­
cularization was present A diagnosis of choroidal osteoma
s h o w s v a r y in g degrees o f d e g e n e r a tio n .
with choroidal neovascularization was made. Hiolodynam ac
The cause of th e s e le s io n s is u n c e r t a i n . 1' " I : " It is
therapy {PD T ) according lo TAP sludy prolocol ithree ses­
u n lik e ly th a t t h e y re p re s e n t t h o t t e l o m a s ; s in c e t h e y h a v e sions at fi weeks' inlerval under fluorescein а п цiojjm phic
b e e n o b s e r v e d t o d e v e l o p i n a d u lt s in eyes t h a t w e re p r e ­ guidance was performed). Following com pi ol ion o f therapy,
v io u s ly u n a ffe c te d (Е -'ig u re 1 4 .2 0 H and l ) . L f> C h o r o i d a l ihe vision improved lo 10/10 :(J). O phthaim oscopkaN y
o s t e o m a s h a v e d e v e lo p e d in p a tie n ts w i t h re c u rre n t b ila t­ a grayish subretinal fibrotic membrane w as noled in the
eral o rb ita l in fla m m a to ry p s e u d o tu m o rs (I'ig u r e L 4 . 2 1 ]£ treated nrea w ilh lota I resolution of subr-minal ffuid and reti­
nal hartQlfKgges ID-:-, C om plete closure p i c h o r d a l neovas­
and F J , ]01 u v e i t i s . . v i t r i t i s , ....... Ila r a d a 's d ise a se (se e
cularization was seen on fluorescein angiogram <E).
fig u r e 3 . 6 0 D - K ) / ' " a n d in th e area o f a p h o to c o a g u la t io n
G - l : D e c a k i f k a t E u n o f c h o ro id a l o s te o m a fo llo w in g P D T .
s c a r .O s t e o m a s in a d u lts m a y e n la rg e d u rin g observa­
I b i s 2 5 -y n a r-o ld a s y m p lo n ra l к w o m a n d e v e lo p e d a c h o r o i­
tio n {H g u re 1 4 .2 0 1 1 a n d R | - L ) S p o n ta n e o u s re a b s o rp tio n dal n e o v a s c u la r m e m b r a n e a sso ciate d w ith an U K tra m a c u la r
o f c h o r o i d a l o s t e o m a s m a y o c c u r . " 1' , ] S t 1 In o n e case c h o ro id a l o s te o m a '.C j . U ltra s o u n d li scan d e te c te d ih e c h o ­
th is o c c u r r e d o v e r a n tf-y e a r p e r i o d a fte r p h o t o c o a g u l a t i o n roidal b u n e ( H ) L She u n d e rw e n t t’ t i T a n d th e c h o ro id a l n e o -
o f a s u b r e t i n a l n e o v a s c u l a r m e m b r a n e . Л11 B ila te ra l o s t e o ­
va s c u la r m e m b r a n e re s o lv e d , as d id the c a lc iu m asso ciated
w ith ih e o s te o m a i hi a n d Г .
m a s h a v e o c c u r r e d in a n M -y e a r-o ld b la c k b o y w h o d ie d
o f a lo n g -te rm illn e s s t h a t w a s t h o u g h t to b e e ith e r h is t io ­ IA - t, : ru n i S .1 il.Ii с ' -.1! w ith p oifkli :■iliti. I--I. Гтот Mnii'IUh <[ J J !
■20QB, Ajric'riLtiri Aiiudi;tttC]h ЛИ lU h ld г е .^ г и ч !.'
c y to s is X o r ю т е f o r m o f s y s te m ic r e a c tio n to a n u n i d e n t i ­
f i e d i n f e c t i o u s o r t o x i c a g e n L . : "' C h o r o i d a l o s t e o m a s m a y
o c c a s i o n a l \y o c c u r i n s i b l i n g s ( H g u re 1 4 . 2 1 A - D ) . 1' 1 1 ',2V2
The d iffe re n tia l d ia g n o s is in th e e a rly sta g e o f th e d is ­
ease, when th e tu m o r has a re d -o ra n g e c o lo r, in c lu d e s o f J a d a s s o h t i . - !cht‘ ■
i u/ O i i e i n f a n t i v i l Ti th is s y n d r o m e had

h e m a n g io m a o f th e c h o ro id , P tP E d e ta c h m e n t, a n d pos­ u ltra s o n o g ra p h ic and o p h th a lm o s c o p ic e vid e n c e o f cho-

te rio r s c le ritis ; in th e la te r stages, d iffe re n tia l d ia g n o s is n o id o s c le ra l o ste o m a s e ? ;L e n d ittg above and b e !o w b o th

in c lu d e s m e ta s ta d c m e l a n o m a , a m e la n o tic m e la n o m a or o p tic nerves a n d e x te n d in g in to th e fa r p e r i p h e r y o f th e

nevus, le u k e m ia , s a rc o id o s is , and d is c ifo rm d e ta c h m e n t fu n d i (b ig u rc I 4 . 2 I ] - K ) . - ' U-1 U ltra s o n o g ra p h ic and com ­

and s c a rrin g . Le s io n s th a t m ig h t he c o n fu s e d u ltra s o n o - p u te d to m o g ra p h ic e vid e n c e of c a lc ific a tio n has been

g ra p ltic a lly and r a d i o l o g i c a l Iу w ith c h o ro id a l o ste o m a s o b s e r v e d in t h e area o f o p h l h a l m o s c o p i e a U y v is ib E e s m a ll

i n c l u d e fo c a l p o s t e r i o r scle ra l o s s i f i c a t i o n in p a t i e n t s w i t h p ig m e n te d c h o ro id a l nevi in Uvo p a tie n ts by ba sta and

h y p e r p a r a t h y r o i d i s m 1' and, in e ld e rly p a tie n ts w it h no a s s o c ia l e s . 206 I n an e ld e rly m an w ho had re c e ive d la s e r

known s y s te m ic d is e a s e (see d is c u s s io n o f id io p a th ic tre a tm e n t fo r a n e o v a s c u la r m e m b r a n e c o m p lic a tin g age-

s c le ro c h o ro id a l c a lc ific a tio n , nest s u b s e c tio n ], p o s te rio r re la te d m a c u la r d e g e n e r a tio n . 1 o b s e r v e d th e d e v e lo p m e n t

s c le ra l o s s e o u s a n d c a r t i la g i n o u s c h o r i s t o m a s th a t i n s o m e o f a c h o r o i d a l o s t e o j n a a d j a c e n t t o a la s e r p h o l o c o a g u l a -

eases m a y be a s s o c ia te d w i t h fa c ial lin e a r s e b a c e o u s n e v u s l i o n s c a r . ilfJ

 F4 .2 3 Id i o p a t hie se n ile scl e ro c h o roid a I ca lcif teat i o r ..
S C L E R O C H O R O ID A L
C A L C IF IC A T IO N A - D : Th is /1-year-old asymptomalic healthy man had m ul­
tiple irfe^ulady elevated yel tow-white suhretinaE ^mijjf.iphic:
Lld e rly p a tie n ts W ith no s yste m ic d is e a s e m ay d e v e lo p I(f^icin-F hcatlered throughout Ihe peripheral fundus o1 hulh
eyes. Ultrasonography demonstrated that these lesions were
m u Il i p ] Ц о fle a i E l-d e fin e d , y e llo w -w h ite , irre g u la r, m u l-
calcified ■ .L?.i.
Lilo b u la te d , q u a d r i l a t e r a I- s h a p e d , p la c o id tjr va ria b ly
E and F: HistopalEroloyy o f an elevated ca lei Fred scleral
e le va te d , c a lc ifie d s c le ro c h o ro id a l le sio n s In th e m id
plaque (arrtw*sf iF^at Was associated wiLh solrte thinning of
p e r i p h e r a l f u n d u s in o n e r a n d f r e q u e n c y h o t h r e y e s [E 'ig u r e the overlying choroid. The retinal detachment is arti factual.
1 4 . 2 3 ) . ' J The le s io n s o c c u r m o s t f r e q u e n t l y in This was an tnci dental find rag in an otherwise normal eye
th e s u p e r o t e m p o r a l q u a d ra n t, b u t m a y o c c u r in a n y q u a d ­ ot" a 7 E-year-old heallliy pilot w ho died in a plane crash.
ra n t. I'h e y a re o c c a s i o n a l l y a s s o c ia te d w i t h s e ro u s re tin a l It is no! known whether this lesion was visible prior lo
enucleation.
d e t a c h m e n t , a h h o u g h th e p a lie n ts are ty p ic a lly a s y m p t o m ­
a tic . The ie s io n s are o f t e n m is ta k e n fo r m e La sta tic c a rc i­
nom a o r la rg e cell l y m p h o m a . A n g i o g r a p h y d e m o n s t r a t e s
m i n i m a l e v i d e n c e o f d e p i g m e n t a t i o n o f th e Ш Ч -. a n d o f t e n O f t e n w id e s p r e a d d is tr ib u tio n o f th e le s io n s a n d fa ilu re

a r e la tiv e ly n o r m a l p a tt e r n o f la rg e c h o r o i d a l ve sse ls a n t e ­ l o f i n d ca lc ific p l a q u e s a n t e r io r t o t h e re c tu s m u s c le s o f t h e

r io r Lo t h e t u m o r s th a t u lt r a s o n o g r a p b i c a l l y a p p e a r Lo b e a ffe c te d eyes su g g e st th a t th e p a th o g e n e s is o f th e s e le s io n s

ca lc ifie d or o s s ifie d p ia c o id tu m o rs in vo lv in g th e in n e r is p r o b a b l y u n r e l a t e d t o t h e d y s t r o p h i c c a l c i f i c a t i o n ( s e n i l e
sc le ra a n d o u t e r c h o r o i d ( F i g u r e 1 4 . 2 3 D J . 2' 2 M e d i c a l e v a l ­ scle ra ] p l a q u e s ) t h a t m a y b e f o u n d a d j a c e n t to t h e o b l i q u e

u a t i o n , i n c l u d i n g c a l c i u m m e t a b o l i s m , is u s u a l l y n e g a t i v e . as w e l l as th e re c tu s m u s c le in s e rtio n s . F ig u re 1 4 .2 3 (E
J h r e e p a t i e n t s Ь а ч-е b e e n t r e a t e d f o r h y p e r p a r a t h y r o i d i s m and ^) d e m o n s tr a te s w h a t m a y b e th e b is t o p a t b o lo g y o f

p r e v i o u s l y / ' 11"31 '■■■ O t h e r m e ta b o E ic a b n o r m a lit ie s a s s o c i­ s e n ile s c le ro c h o ro id a l c a lc ific a tio n . I'h e c lin ic a l s e ttin g
a te d w ith s c le ro c h o ro id a l c a lc ific a tio n in c lu d e h y p o m a g n e ­ and th e a p p e a r a n c e o f th e s e le s io n s s e rv e to d iffe r e n t ia t e

s e m ia a n d renal tu b u la r h y p o k a le m ic m e ta b o lic a lk a lo s is t h e m fr o m o t h e r c a lc ifie d le s io n s a ffe c tin g th e c h o r o i d a n d

s y n d r o m e s [ B a r t t e r o r f f j E f e l m a n s y n d r o m e ) / 14' sc le ra ( o s t e o m a s , h e m a n g i o m a s , a n d m e l a n o c y t i c n e v i ) .
S c i e r o c h o r o i d a ! C a r t ila g e F 4 .^ 4 M u ltip le n e u r o m a s a s s o c ia te d w ith th e m u ltip le
e n d o c rin e n e o p la s ia s y n d r o m e ,
Lin e a r sebaceous nevus o f Jadassohn can be A s s o c ia te d
w i t h a n t e r i o r e p i h u l b a r c h o r i s l o m a . ' 1 ' Еп r a r e c a t e s , p o s t e ­ Л - G : N t ) L e p r o t r u d i n g t o n j u n c i iv al n e u r o m a s ( a j t o w r A ii n d
r i o r scle ra l c a r t i l a g i n o u s c h o r i s t o m a s t h a t r e s e m b l e c h o r o i ­ Cj n t-iir u p p e r-1 id n iLifg in . ih e [h ic k e -n td lip s and p o ittn y -

d a l o s t e o i q a o p h t b a l m o s c o p t c a l l y h a v e b e e n o b s e r v e d .21* r o i d e t l u m y s e n r ( a r r o w , LSI, a r a c h n o d a c l y l y I t ) : , L o n g u e n e u -
te m a s (a jfra w , E), e n la rg e d co rne al nerves >1-), a n d rope I i k e
e n l a r g e m e n t o f t h e L e m p o i a l fc rn g c i l i a r y n e r v e ( a r r o w , C > .
C h o r o i d a l C / lia rv N e u r o m a s A s s o c i a t e d w ith H and I: H is t o p a t h o lo ^ y o f e n la rg e d lo n y b ilia ry n e rv e (lo w -
M u l t :p i e E n d o c r i n e N e o p la s ia T y p e It-A p o w e r VieVS A n M , 14 ■ a n d e n la rg e d b d n jirn c tiv a l nervet aI
ih e lim h u H (h iflh -p tjw e r v i r w , 11 i n a n o l h e r p a t i e n t w ilh ih e
M u I l i p Le e n d o c r i n e n e o p la s ia (M EM ) ly p e 3 1-Л is a s y n ­
н а т е d is o rd e r.
d r o m e c o n s is tin g o f m e d u lla ry c a rc in o m a , m a r fa n o id h a b ­
itu s . t h ic k e n e d lip s , s k e le ta l a b n o r m a l i t i e s , a n d n e u r o m a s I hi and t, jrtpm SpeiJDC Ы al.JS7t

o f th e c o rn e a l n e rve s , c ilia r y n e rve s , a n d m u c o s a , in c lu d in g

tbe c o n ju n c tiv a and m o u th [h ig u re 1 4 .2 4 ) .*'° The rope­
lik e e n la r g e m e n t o f th e lo n g c ilia ry n e rv e th a t is v i s i b l e
t e m p o r a l l o t h e m a c u l a a s it c o u r s e s t h r o u g h t h e c h o r o i d
(I'tg u r e 34 . 2 4 C } is u n a s s o c i a l e d W ith a lte ra tio n in v is u a l N e u r o fib ro m z

f u n c t i o n , t r o p h y t a c t i c t h y r o i d e c t o m y is r e c o m m e n d e d lo S o lita ry c h o r o id a l n e u ro fib ro m a o c c u rs s p o ra d ic a lly and

p revent m o rb id ity a s s o c ia te d w ith m e d u lla ry c a rc in o m a s h o u ld b e c o n s id e re d in th e d iffe re n tia l d ia g n o s is o f a n
th a t in v a r ia b ly d e v e lo p s in th e s e p a lie n ts . H i s t o p a t h o lo g i c a m e la n o lic c h o ro id a l m e E a n o m a .- - '1 D iffu s e n e u ro fib ro ­
e xa m in a tio n o f th e a ffe c te d b ra n c h e s o f ih e c ilia ry n e rv e s m a s g e n e ra lly o c c u r in a s s o c ia tio n w ith n e u ro fib ro m a to ­
s h o w s h y p e rp la s ia o f th e p e rin e u ra l and s c h w a n n ia n tis­ s is t y p e I p re s e n tin g as a tria d o f u n ila te ra l h u p h lh a lm o s .
s u e . 2i": f i f t y p e rc e n t o f cases o f ty p e ll-H M B N occur spo­ h o m o i a t e r a ! e>re l i d p l e f c i f o r m n e u r o f i b r o m a , a n d b o m о l a t ­
ra d ic a lly ; Г>0% are in h e r ite d as a n a u to s o m a l d o m i n a n t . e r a l f a c ia l h y p e r t r o p h y (E -'r a n ^ o is s y n d r o m e ] . 1
S H e n ic h tyf^ d n l tS g trijk n tiim I22 7
Schw annom a [ 4 ,2 5 U v e a I sch w a n n o m a ,

U v e a l s c h w a n n o m a е л и p r e s e n t as a s o l i t a r y ( u m o r i n l h e Л - J : Л 4 7 -y e a r-o ld w h ile m ale p re s e n te d w ilh g ra d u a l, p ro ­

c i l i a r y b o d y a r c h o r o i d , o r d i f f u s e l y i n t h e w h o l e u v e a / - 11 gressive b lu rrin g o f v is io n in his EefL e y e (2CV5DJ. S liL-ta m p
'J V p ic a lly , u v e a ! s c h w a n n o m a p r e s e n t s as a s o l i t a r y a m e l­ e x a m in a tio n o f Iht1 Ipfft e ye re ve a le d a d o m e -s h a p e d c :lio -
an o tic lu m o r ( I'ig u r e 1 4 . 2 5 ] . J J -' M u ltifo c a l p le x ifo rm LhfjroiclLil mass i A ) . 31-st я п u ltra s o n o g ra p h y d e te rm in e d the?

s c h w a n n o m a h a s a ls o b e e n r e p o r t e d .- '-''
d im e n tLo n ^ o f lh e d o im ^ -sh a p e d I ем o n to Pie ~\7 X 1 S n in i
Ibase) w it h л h e ig h t ot 1 1 . 4 m m . D e fin ite Intrinsic va s c u la r­
ity c o u ld r e t b e o b s e rv e d , t b e lesion a ls o h a d a c o u s tic v o id .
U v e a ! L e io m y o m a
1 hurt' w u i n o e v id e n c e o f e .x th is |3 e H extens io n 40). A -sea rl
L e io m y o m a is. a b e n ig n , s m o o t h - m u s t le tu m o r o f lh e u llra s o n o g fa p h y s h o w e d л h ig h initia l spike w ith m e d iu m
u v e a , m o s t o f t e n a ris in g in th e c tlia iy b o d y a n d iris. '" n ' internal re fle c tivity ( Q . F o llo w in g in cis io n a E b io p s y th a t
22' a n d o c c a s io n a lly in th e c h o r o id ," '*" ''- 1 o r c a n e x te n d
L o n fir m e d the d ia g n o s is , surgical e x c is io n o f c iiio c h o ro id a l
s c h w a n n o m a fro m s u p ra c h o ro id a l sp a ce w a s p e rfo rm e d iD f .
in to il f r o m t h e c i l i a r y b o d y , it is n o n p i g m e n t e d o r a m e l -
F u n d u s p b o lu g ra p h o f Lhe left e y e ta ke n 3 m o n th s fo llo w in g
a n o tic , a n d lets m o r e lig h t t h r o u g h on t ra n sillu m i n a t i o n
e x c is io n s h o w in g n o rm a l m a c u la w ilh v is io n o f 2(V2E> (E F
com pared to an a m e la n o tic m e ta n o m a . O fte n it a rise s
Lig h l m ic ro s c o p y s-howi-ng s p in d le celts in p a lis a d in g paLLern,
in Lhe s u p m c h o ro id a l aspect and pushes Lhe c h o ro id a l H flfn u n rifjis lo c h e m teal s la iii1- o f c H ja c h o ro id d l mass, w e re
s tro m a m w ards when th e te s io n can appear p ig m e n te d . BjegaliVe for C.il ‘ H i 5 M A a n d p o s itive fo r (I) 5 - 1 0 0
S e n t i n e l b l o o d v e sse ls a n d e x tr a s c le r a ! e x t e n s i o n c a n o c c u r i!-.. E le c tro n m icntTM iopy s h o w in g s p in d le d (e lls w :lh e lo n ­
s im ila r to a m e la n o m a . ! n a l!. E C ) - 9 0 a o о с ш г in fe m a le s , gated m u 'lei a n d b k in d fcyihplasrn lj).

w ith preponderance- In young a d u lts d u rittg re p ro d u c­ L eio m y o m a

tive a g e . :l It Ю з у b e a sso c ia te d w ilh u te rin e le io m y o m a K —.V t: A С m e a s is n m a le p re s e n te d w ilh a c ilia ry b o d y m ass
tn s o m e .'" " A b rig h tly transi H u m m a tin g , n o n p ig m e n te d in lh e i n f erejnn Sri I qusdlrant o f his right e y e (K j. The H in ­
Lum or Lhat Lo c a lize s to Lhe s u p r a m 'e a l space on c a re fu l dus W as o th e r w is e n o r m a l. A b io p s v re v e a le d [he m ass lo
u lt r a s o n o g r a p h y in y o u n g a d u l l fe m a le s su g g e sts a c lin ic a l
be a le io m y o m a that w a s estrogen n e c e p to r-n e g a Live . H e
w a s trea ted w rlb a n a s Lro zo le a n d the Lu m o r s h ra n k in s ize .
d ia g n o s is o f le io m y o m a ." ' Fin e -tie e d le a s p ira tio n h io p s y
U ltra s o u n d В scan o f Lhe m ass in 2 0 Q B b e fo re tre a tm e n t (Lf
m ay be h e lp i'u l. H is to lo g ic a lly , th e Lu in o r shows b la n d
H nd 1 years fo llo w in g tre a tm e n t ( M l s h o w e d t e d u c tifr i ir:
n o n p ig m e n te d s p i n d l e c e lls w i t h a b u n d a n t c o n n e c t i v e tis ­ h e ig h t o f Lhe le s io n .
sue. t’ o s i L i v e s m o o t h - m u s c le a n tig e n and m u s c le -s p e c ific
I A ■, 'm m lu r c J I e l . 1 1 , slh, [ х т т г т м ч п п : К \ f l, tiu LirlL -sy 11 I U r. C .ir :i<
act in h e lp c o n firm (h e d ia g n o s is . S o m e o f th e m m ay be S h ie ld - iLrn l M r к г г у S h in'ld -.

e stro g e n re c e p to r-p o s itive .

S m a ll tu m o rs can be observed; la rg e r ones if con­ e stro g e n re c e p to r-n e g a tive , re sp o n de d w ith s h rin k a g e
f i r m e d b y b i o p s y ca ii b e re s e c te d t h r o u g h a s u p r a c h o r o i d a l (fig u re 1 4 .2 5 K - M ) .
a p p r o a c h . ' 1" T h e L u m o r is b e n i g n w i t h a n e xc e lle n t p r o g ­ R b a b d o m yosarcom a is a m a lig n a n t m esenchym al
n o s is . Dr. S h ie ld s has used a ro m a ta s e in h ib ito rs [a n a s ­ t u m o r o f c h i l d h o o d ( h a t c a n r a r e ly a r is e in t h e iris a n d c i l i ­
Lro /o le J in a m a le p a tie n t whose lu m o r. d e s p ite b e in g a r y b o d y , b u t is n e v e r r e p o r t e d i n t h e c h o r o i d .

ш J
Ц , и М иш I

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R EA C T IV E L Y M P H O ID i4 .^ 6 R e a c tiv e ly m p h o id h y p e rp la s ia o f lh e u vea l
tra c t s im u la tin g d iffu s e m a lig n a n t m e la n o m a or
H Y P E R P L A S IA O F T H E U V E A m e ta s ta tic c a rc in o m a .

D iffu s e b e iiig n re a c tiv e ly m p h o id h y p e rp la s ia in vo lv in g A - £ : A 5 5 -y e a r-o ld w o m a n fta v t a 2 '/j-yaa r b is lo ry aJ recu r­

th e c h o r o id , c ilia ry b o d y , and iris u s u a l l y I n one eye of ren t -episodes o f U n e x p la in e d m e La m o rp h o p s ia a n d b lu rre d
vis io n in ib e riy h l e y e . V is io n in lh e ri^hl e y e w a s 2 0 /4 0 0 a n d
o th e rw is e h e a lth y m id d le -a g e d o r o ld e r in d iv id u a ls [m e a n
in fhe feit eyfi w a s 2 0 / 2 0 . H e r e ^o p h itK b lM a in e flcr r e a d i n g
a g e 5 5 y e a r s } is a r a r e c l i n i c a l s y n d r o m e t h a t is d i f f i c u l t l o
w e re righl e y e 2 0 a n d left eye 1 9 . Th e extrat jc u I hi m o :e -
d ia g n o s e a n d m a y r e s e m b le in a ll respects m e ta s ta tic c a r ­
m e n ls w e re fu ll. T h e e ve s w e re n o L in fla m e d . G u n io s c o p y
c in o m a o f th e c h o ro id (se e p. 1 2 3 6 ) .. d iffu s e m a lig n a n L re v e a le d a to ta lly o c c lu d e d апцГе o n the ri^ h t. T h e c ilia ry
Lym phom a o f t h e u v e a l tra ct [se e p . 1 2 2 4 J, d iffu s e a m e l- processes a n d pars p ian a W e r i re a d ily v is ib le ihnouj^h a n
a n o tie m e la n o m a (se e p . 1 2 0 0 ) , o r d i f f u s e u v e a l m e Ia n o - u n d ila le d рирЁЕ. H ie in tra o c u la r p re ssu re w a s 35 m m Н у in
c y tic p r o l i f e r a t i o n a s s o c ia te d w i t h s y s te m ic c a r c in o m a (se e
lh e rij;hl № e a n d 1 7 m m H g in the lefl e y e irefore a n d aftejt
p u p illa ry d ila lio n . There w a s a d iffu se ye ll a w diiicol oral io n o f
p. l f f l Q 2 ) 2^ ] " 3iT P a lie n ts w rtth b e n ig n re a c tiv e ly m p h o id
lh e fu n d u s a ttrib u la b le I и c h o T o id a l th ic k e n in g a n d a lte ra tio n
h y p e rp la s ia m a y c o m p la in in itia lly o f re c u rre n t e p iso d e s o f
o f the n o rm a l c h o ro id a ] p ie m e n lacy p a llc rn ( A a n d LS:. T b w e
b lu rre d vis io n and m e la m o rp h o p s ia se c o n d a ry to se rou s
was- a serous m a c u la r d e la c h m e n l. T h e fu n d u s q f Lhe A l l e v e
d e t a c h m e n t o f t h e m a c u l a a n d b e m i s d i a g n o s e d as h a v i n g was n o r m a l. Th e e y e w a s e n u c le a te d b a ia u s e o f s u sp ected
! d i о p<:. I h i с i a I so re uts. r h o : i о r e t i :n: а УIi v I -.ve n t u a l l у i :'- d iffu se m e la n o m a . H is to p a th o lo g ic e x a m in a tio n re v e a le d
fu se , o c c a s io n a lly u n d u la t in g t h ic k e n in g o f th e u v e a l tract that lh e u v e a l LracL w a s d iffu s e ly th ic k e n e d a n d ini ill rated
b e c o m e s m a n ife s t (F ig u r e 1 4 .2 6 l :). Ih e fu n d u s d e v e lo p s a w ith m a tu re ly m p h o c y te s a n d ly m p h o id follicEes (C a n d
D k N o l e e x le n tio n o f ini ill rate irilo [h e re tro b u lb a r Iissues
y e llo w is h -g ra y c o lo r w it h d e p ig m e n ta tio n and m o ttlin g o f
la rro w , C ) . l'h irly years biter s h e re lu m e d b c cau se o f the s lo w
th e К Р Ё , loss o f t h e n o r m a l c h o r o i d a l o s c u l a r m a r k in g s .,
d e v e lo p m e n t u f ;i s m o o th , ele va led .. p in k SLibconj-unclival
and fo rm a tio n o f lin e a r stre a ks s e p a ra tin g areas o f u n e v e n in fill rate in Ihe left e y e <E) I ha I re m a in e d U n c h a n g e d d u rin g (:■
c h o ro id a l in filtra tio n { ]:ig u re 1 4 .2 6 A , 11, E> a n d C i). in rtionths o f fo llo w -u p . 11 p re s u m a b lv has lb e sam e m S lD p a th o -
s o m e p a t i e n t s t h e u v e a l i n f i l t r a t e b e g i n s as m u l t i f o c a l y e l ­ lo y ic fin d in g s as in the u v e a l tract o f the rig h t e y e . H e r left
lo w -o r a n g e le s io n s o r as m u ltifo c a l c re a m -c o lo r e d le s io n s e ye is a th e rw is £ n o m ia J . i h e n e v e r d e v e lo p e d E v id e n c e o f
s u p e rim p o s e d o n th e d iffu s e y e llo w is h c o lo r c h a n g e caused
re c u rre n c e o f lh e i rMia m m at io n in I be righl o r b it.
F - L : i a m e d ise ase in th e right e y e (E l o f an 8 4 -y e a r-o ld
by Lhe c h o r o id a l i n f i l t r a t i o n ." 1" " ''" t]i n k , s m o o t h - s u r f a c e d
w o m a n w ilh m ild ritjhl p ro p lo s is a n d v is u a l a c u ity ol' 2 1 У 4 М
s u b c o n ju n c tiv a l e x te n s io n s o f th e l y m p h o c y lic in filtra tio n
in the rig h t e ye a n d 2 0 / 2 0 in tb e lefl e y e . N o t e [h e irre g u ­
occur in som e cases (H g u re 1 4 . - 2 & H ) . 1" 1 S m a l l e p ib u lh a r
la r th ic k e n in g o f th e c h o ro id p o s le rio rJy a n d loss u f c h o r o i­
n o d u la r e x te n s io n s o f th e in filtra te th r o u g h lh e p o s te rio r d a l va s c u la r m a rk in g s (Ef c o m p a r e d to Ihe n o rm a l left e ye
e m is s a ry scle ra l c a n a ls occur fre q u e n tly . th es e n o d u la r I F :. N o t e irre g u la r pa tlern o f pi|^m enL e p ith e Jia i d e m a rc a ­
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u s u a lly are d is c o v e re d in c id e n ta lly d u r i n g u ltr a s o n o g r a p h y (C ). A n ^ io ^ r a m s s h o w e d lnvp ofluoroH con t linen in the v a lle y s
sepa ra ting b ro a d ^ o n e s o f irre g u la r c b o ro id a ] th ic k e n in g OH
o r c o m p u t e r i z e d s c a n n i n g o f t h e o r b i t . " ' 1'' " +J A s t h e c i l i a r y
a n d ll. C Jom puLed to m o g ra p h y s h o w e d d iffu se u v e a l Iracl
body becom es d iffu s e ly In v o lv e d , th e a n te rio r-c h a m b e r
th ic k e n in g a n d re lro h u tb a r e x te n s io n o f the infEttrale (a rro w ,
a n g le m a y n a r r o w a n d cause acute a n g le c lo s u re g la u c o m a . 1 1. C o m p a r is o n o f u ltra s o n o g ra m s b efore a n d after tre a tm e n t
tjK le n s ive re tin a l d e t a c h m e n t m a y o c c u r A la r^ e te a r in th e w ith system ic c o rtic o s te ro id s re v e a le d re d u c tio n o f uveal
R F E o c c u rre d in o n e e ld e rly p a tie n t w it h p o ly c lo n a l h y p e r - th ic k e n in g >K a n d L;-.
g a m m a g l o b u E m e m i a . ' ' ' 1" Karl у p h a se s o f flu o re s c e in a n g i­ | A - D r frtWn (J.L5-." 11 p u b l i i h t d Ц1.-1 iFi pxj rrrii iM o n Iro m I hit! А л ч и гк ^ п
o g r a p h y re ve al irre g u la r m o t t le d areas o f h y p e r flu o r e s c e n c e loum.tl Ltf t)plYlh.ilntolGj;y; cupyrii^il by T he U p M t a l m i c : Publishing C b .
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c a u s e d b y t h e c h a n g e s i n t h e IfcPE a n d a s e rie s o f b y p e r f l u o -
ri yhi!: rustrvcM.!. I
re sc e n t lin e s d e m a r c a t i n g z o n e s o f irre g u la r t h ic k e n in g o f
t h e c h o r o i d { i ' i g u r e 34 . 2 6 H a n d i ) . l i i t e r - p h a s e a n g i o g r a m s
№ ow e vid e n c e o f m u ltifo c a l a re a s o f s t a i n i n g at t h e le v e l p r o l i f e r a t i o n (1-ig u re 1 4 .2 6 J ) . M ■U l t r a s o u n d ly p ic a l l y s h o w s
o f th e ftP E. C o m p u te d to m o g ra p h y and u ltra s o n o g ra p h y a s m o o th , lo w re fle c tiv e t h ic k e n in g o f t h e u v e a l tra c t a n d
d e m o n s t r a te d iffu s e t h ic k e n in g o f t h e u vea l ira c l as w e ll as o n e o r m o r e e p i b u l b a r e x te n s io n s o f th e in filtra te (fig u re
th e p o s te r io r n o d u l a r e p isc le ra l e x te n s io n s o f th e l y m p h o i d I 4 . 2 6 K a n d I.).
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have m u ltis y s te m re a c tiv e ly m p h o id h y p e rp la s ia (fig u re
b o lb orF>iLs a n d c h u e k i 'A j . f u n d ик p H & to g ra p h o f the Til’ ll I
14 .2 7 J .j r H v e n i f s y s te m ic in v o lv e m e n t o c cu rs, th e p r o g ­ в уе o f the злгпе p a tie n t re ve a ls c re a m y c h o ro id a l lesions
n o s i s f o r li f e i s g o o d . ^ ! co nsistent w ilh u v e a l re a c tive h y p e rp la s ia <EJ). T h e lelt fu n -
I t l s t o p a t h o l o g i c a l Iу ih e uveal ira c l is in filtra te d p re­ flu-. h a d s im ila r f i n d i n g E Q . O p t ic a l coherence? t o n K g r a p h y
d o m in a n tly w ith w e ll-d iffe re n tia te d ly m p h o c yte s , o fte n dom om strnles c h o ro id a l Lriicken in ^ ( D ) : M a g n e tic r g s o m n C e
im a ^ in ^ o f Ihe sam e p a tie r t d e m o n s ! rates btFateral lacrim al
w i t h re s id u a l g e r m in a l c e n te rs [t'ig u r e ] 4 . 2 6 C a n d D ) .T h e
^ la n d s w e llin g 1:1. F (in s p i:, IJiopn y e x b iliile d fo]3ic3esi Ihai
Ly m p h o id p ro life ra tio n Is p o ly c lo n a l. D e te rm in a tio n o f
w u Ty sep a ra te d b y w id e m le rfo licLilar aruas w]ch p r o m i пел I
t h e c l o n a l i t y o f t h e l e s i o n is o f l i t t l e p r o g n o s t i c v a l u e . ' ' 1'1
m a n tle го п с ъ . Fhte follicles w e *e c o m p o s e d o f a p le o m o r­
B io p s y o f e ith e r a n a n t e r io r o r p o s te r io r e xtra s c le ra l n o d - p h ic F y m p h o id ceil p o p u la tio n , in c lu d in g d e n d ritic cells a n d
u Je o r o f th e c h o ro id is h e l p f u l in e s t a b lis h in g th e d i a g ­ Lin ^ib le b o d y m a c ro p h a g e s i.a rro w l. S o p o iyk -a ryo c y le s irnul-
n o s i s / ’ 11,1' " A correct d ia g n o s is of re a c Live ly m p h o id tinucleatEK f d e n d ritic cells) w e re fo u n d , tvtitoric figures w e re
h yp e rp la s ia versus fo llic u la r ly m p h o m a can he re lia b ly
rt'^icJi ly a p p a re n t (F :.

e s t a b l i s h e d e m p l o y i n g i m m u n o h i s t o c h e m i c a l m e t h o d s . ■ ''' ll-mm S[.k v' '■'l л1" ' ' wilh rjrrmihbion.'i
I f a ll s tu d ie s f o r t h e p re s e n c e o f m e ta s ta tic d is e a s e a re
n e g a tiv e ., m o d e ra te ly heavy doses of s y s te m ic c o rtic o ­
s te ro id s m ay be su c c e ss fu l in c a u s in g re s o lu tio n o f th e
uveal in filtra tio n (Fig u re 34 . 2 6 К and L ) . ~ 3J A s th e in fil­
t r a t e r e s o l v e s , it l e a v e s v a r y i n g d e g r e e s o f c o a r s e l y m o t t l e d
d e g e n e ra tive changes in th e R T F L o w -dose irra d ia tio n
m a y b e n e c e s s a ry in s o m e cases t o e ffe c t r e s o l u t i o n o f th e
d is o rd e r.
t ^ i t t m g e r 'r e p o r t e d a s im ila r uveal in filtra tio n w ith
m u ltip le cream y u 'h it e s u b re tin a l le s io n s and e xu d a tive
re tin a l d e ta c h m e n t and m ild p ro p to & is in a 2 1 -y e a r-o ld
p a tie n t w ilh C a s t l e m a n ' s d i s e a s e . ' I ’h i s is a l y m p h o p r o l i f -
e ra tiv e d is o rd e r c h a ra c te rize d by a th y m o m a -lik e m ass
w ith h y p e rp la s tic ly m p h o id fo llic le s w ith a c c o m p a n y in g
c a p i ll a r y a n d e n d o t h e l ia l h y p e r p la s ia a ris in g in th e m e d i ­
a s t i n u m ." ' ' 'I h e u v e a l le s io n s r e s p o n d e d to 2 Q t i y g iv e n in
d iv id e d doses.
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surgery in l)i)i 11 W it h in -a m o n th erf surgery, h e n o tic e d
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l y m p h o m a is a v a r i a n t o f o c u L n i r a d n e x a l l y m p h o m a r e p r e ­ e x a m inal io n w a s negative*. O n fu n d u s e x a m iп Ш io n , small
s e n t i n g a l o w - g r a d e n o n - ] E o d g k i n 's ti-c e il l y m p h o i d m a l i g ­ oval-sE^aped y e llo w lesions w e re o b s e rve d Lhal w e re scat-
nant п е & ш . 1 : T h e c lin ic a l fe a tu re s a re s i m il a r to l h a l K^red I Ei ro u g h tw I lEru d u a d d in Ею1Ь eyes w ith c o n flu e n c e in
the.1; m a c u la r a n d le m p o ra l ruf^ions In lin 1 righL e y e . There w e re
o f re a c tive l y m p h o i d h y p e rp la s ia a n d i t is b e l i e v e d t h a t .,
no vitre o u s cells :A a n d til. hlu<jtfescein angiugriaphy s h a v e d
i n t h e p a s t, a v a s t m a j o r i t y o f cases th a t w e r e d i a g n o s e d l o
ea rly hypol luurescence w iLh Ial*: h y p e rliu o re s c e n c e сотги -
haw re a c tiv e l y m p h o i d h y p e r p la s ia w e re i n f a d E o w -g r a d e
s i m d i n g l d the d is trib u tio n o f th e c h o ro id a l lesions IC a n d D : .
i y m p h o m a . J 'I 'i , 2 ‘l * " i h e o c u l a r i n v o l v e m e n t c a n be u n ila t­ O p t i c a colrcnenco (о т о й Н р Е т у c o n firm e d sign ificanl ele-va-
e ra l o r b ila te ra l a n d m a y h a v e e jtlra u ve a l e x t e n s io n s u c h as Li-on o f lhe retina w ilh s h a llo w su brelinal flu id . M a g n e tic reso­
s a l m o n p a tc h le s io n v i s ib le in Lhe a n te r io r o r b it o r s m a ll n a n t e im a g in g o f Lhe brain a n d orbils s Fiow ed no in fraorb ital
areas o f e xtra s c le ra l e x t e n s i o n d e te c te d b y u lt r a s o n o g r a p h y
mass lesions o t a b w i)ггпчч! en h a n c o m e n l o f a d n e xa l tissues.
L o m p le lo b lo o d c o u n t, -C M F a n d с о т р и Led to m o g ra p h y o f
[E 'ig u r e 1 4 .2 Й } . ]h e p a th o lo g ic d ia g n o s is is b a s e d upon
Lhe chesl, a Eid o m e n , a n d p e lvis w e re nega live r'or Iv m p h o m a .
c o m h illa tio n o f h is to lo g ic , im m u n o h is to c h e m is lry . flo w
A Ira nsvi I real fin e -n e u d le aspiration b io p s y o f Ihe c h o ro id a l
c y to m e tr ic , a n d g e n e r e a r r a n g e m e n t s tu d ie s th a t are u s e d lesion w a s p e rfo rm e d in Ihe right e v e ; Lhis w as c o m p lic a te d
to d ia g n o s e a n d c la s s ify l y m p h o m a s . A t h o r o u g h s y s te m ic by transient vitre o u s a n d suE)reiinal h u m o rrh a g e (I... T h e c y to l­
in v e s tig a tio n , at in itia l d ia g n o s is and p e rio d ic a lly th e re ­ o g y e v a lu a lio n a lo n g w ilh flo w c y lo n iu try s h e w e d in te m iu -
a fte r. s i m i l a r to Ihat u n d e rta ke n f o r p a tie n ts w i t h o c u la r dialu and s m a ll, O J 5 - + , C U 2 0 - В cells, expressing
adnexal Lym phom a, is m a n d a to ry to de tec t ly m p h o m a p re d a m rnnnflv la m b d a ch a in s. These f i n d i n g w e re c o n *is -
Lenl w ith a lo w -g ja d e n o n -H o d ^ Jtin 's ly m p Ere m a . T h e p a tie n t
e ls e w h e re . Tre a tm e n t o p tio n s in c lu d e lo w -d o s e ra d ia ­
was Irealed w ilh hilaLeral radial ion llitinspv to la lin g З О Й у in
tio n [ 3 0 G y ] g i v e n tn d i v i d e d d o s e s i f o n l y a s i n g l e siLe is
d iv id e d d oses. AJt S п к т И п - p o sttre a tm e n t, Lhere Was c o m p le te
in v o lv e d o r s y s te m ic targ e te d th e r a p y w i t h C D 20 a n t ib o d y
ru s o lu lio n oi Liveal ly m p h o m a ;l-.i.
( r i t u x i m a b ) i f l y m p h o m a is m u l t i f o c a l .
M e t a s t a t ic u v e a l l y m p h o m a .
Uveal in vo lv e m e n t w ith ly m p h o m a m ay a ls o occur
G - L : A З в -y e a r-o ld H is p a n ic т а Г е p re s e n te d w ith floaLers in
as a m e t a s t a t i c e v e n L i n t h e s e t t i n g o f a p r o g r e s s i v e h i g h -
b o lh eyes o f L m onLh"s d Liia lio n c a u s in g a visual d e c lin e 1o
grade n o n -H o d g k in 's ly m p h o m a (Fig u re s I4 .2 S G - L and
c o u n i in-g fingers I fo o t i.30c n r in lh e righL a n d 20 -'200 in the
1 4 .2 9 A - E - ') ' o r E lo d g k in 's l y m p h o m a (J:ig u re 34 . 2 £ C - L ) . lefl e y e . H e u n d e rw e n l a d ia g n o s tic a n d p o s s ib le th e ra p e u tic
S u c h cases s h o u l d b e e v a lu a t e d a n d tre a te d b y a n o n c o l o ­ vilrut Lo m y . H is past m e d ic a i history w a s s i^ n ific a n l Гсэг testic­
g is t d e p e n d i n g o n th e o v e r a ll s y s le m ic s ta tu s . u la r n a tu ra l k ille r/T-c e ll n o n -H o d g k in 's ly m p h o m a for w h ic h
he h a d h a d a n o rc h ie c to m y , a n d re c e iv e d in lra v e n o u s a n d
fnlrathecaE cEw m o C h e rap y a n d ra d ia tio n for sinus m etastasis.
F o lk y w in g v itre c to m y Ih e fu n d u s re v e a le d m u ltifo c a l c re a m y
w h ile c h o r o id a l lesions w ith o v e rlv in g s u b re lin a l flu id in
Ejolh eyes \ C i. F lo w c y lo m e try re v e a le d C JD 2 + , 0 3 3 e + ,
a n d С 1Э 5 6 - T cells; p o ly m e ra s e c h a in r e a d io n w a s p o s iliv e
for tp s L e in -B a r r viru s a nti n e g a live fo r to x o p la s m o s is , h erpes
s im p le x v iru s , herpes zo s le r viru s , c y to m e g a lo v iru s , h u m a n
T-1 ym p h o l ropi с v iru s , arcrl b acleria l a n d fu n g al си I lures. H e
re c e ive d m lra v itre a l m e lh o tr e x a le lo b o lh eyes, w h ic h p ro ­
gressively n e s b lvtd lh e lesion s le a vin g Eje h in d a le o p a rd -s p o l
fu iid u s a p p e a ra n с e т с ч е т Ь М п ^ b ila le ra l d ifl;.ise u v e a l m u la -
n o c y lic p ro life ra tio n (J—L ) . I h e lesions w e re h y p o a u lo flu o ­
rescent 'l-El a n d s h o w e d transm ission Iw p e rflu o re s c e n c e on
an^icii’ Taphv ! ) . H is v is io n im p ro v e d к ) 2 0 / $ Р a n d 2tlb''4f>.

Гг■■ 111 I - 'j I I l t u I ,lI." w it h purnhiMLiun: L j - L , ■

: o u rlc s ;, ■:: P i 1чпп
Н и .ш ц . I
1&№(/) Lifm piow n I 235
 F4. M e t a s t a t t e u v e a I l y m p h i >in a „
C H O R O ID A L M ET A ST A T IC
TUM ORS A - F : A 5 1 -y e a r-o ld fe m a le p re s e n te d w ilh c o m p la in ts o f
bilateral fe d eye o f 2 w e e k s ' d u ra tio n associatud w ilh p h o -
ra tie n ls w ith m e ta s ta tic c a rc in o m a tp th e c h o ro id m ay lo p h o b ia a n d b lu rre d v is io n . i b e had b e g u n a series o f c h e -
m o lh e ra p y reyim -cnt 1 7 m o rp h s p re v io u s ly for ппл nl Iс te ll
d e v e lo p serous, and o c c a s io n a lly h e m o rrh a g ic , re tin a l
ly m p h o m a lh-al c u lm in a te d in a u to lo g o u s stem cell Irans-
d e ta c h m e n t in v o lv in g ih e m a c u la (h ip u re 1 4 . 3 0 )."■ ■'1 " J : "
p la n ta lio n . O n p re sen tation , she w as re ce ivin g p tu jjirn a b in
O p h th a lm o s c o p ic e xa m in a tio n ty p ic a lly reveal л a p a le
c o m b rn a lio n w ith intrathecal c y ta ra b fn e fo r le p to m e n Ln g e a l
w h ite or y e llo w -w h ite c h o ro id a l le s io n u n d e rly in g th e in v o lv e m e n t. Visual a c u ity w a s 2 ( ^ 4 0 in Lhe ri^ht e y e .in d
serous d e ta c h m e n t. О ra n g e -c o lo re d c h o ro id a l m e ta s ta s is c o u n t finders al 1 to o l (30crrt^ in the left e y e . Exte rn a l e x a m i­
m a y l o c a l i z e t h e p r i m a r y t u m o r to t h y r o i d g l a n d , k i d n e y s n a tio n re v e a le d m u ltip le cu ta n e o u s eyelid n o d u le s bilater­
or lu n g s [c a rc in o id }. M arry m e ta s ta tic le sio n s are o n ly a lly a n d s a lm o n patch in lh e su p e rio r fo rn ix o f th e rfgjbt e ye
( A a n d H j. ilit - la m p e x a m in a tio n w a s significant for p s e u d o h y -
m ild ly e le va te d (3 m m o r le ss), hut th e ir g ro w th p a tte rn
p o p y a n , irregular s t o m a l lliic k e n in i’ o f iris, a n d vitreous- culls
m a y s im u la te th a t o f a m e la n o m a in e v e r y w a y . C o a r s e .,
11 el! evie m o re ih a n ri^ht) b ila te ra lly. She w as p la c e d o n h o u rly
m o t t l e d d e p i g m e n t a t i o n a n d c l u m p i n g o f t h e R P t i a re fre ­
p re d n is o n e e y e d ro p s . In a d d ilio n , e x te rn a l-b e a m ra d ia lio n
q u e n t l y p r e s e n t , '['h e r e m a y b e m u l t i p l e le s io n s in o n e o r tre a lm e n t at a dtw e o f I - E G y iseve n t'raclionsi w a s a d m in is ­
h o t h e y e s (S 'ig u re 1 4 . M D a n d 1 1 ). E ' l u n r e s c e i n a n g i o g r a p h y tered as a c o n e d o w n to the area o f gross o c u la r disease, w ith
u s u a lly re v e a ls a n irre g u la r, w id e s p r e a d a re a o f flu o re s c e in an a d d itio n a l dose o f l b C y (eight Iraclions) to Ihe b rain ( C
le a k a g e f r o m th e s u rfa c e o f th e le s io n ( fig u r e 1 4 .3 0 b , C r Fr a n d D ) . O n e w o e k fo llo w in g [initiation o f e x te m a l-b e a m in d ia -
Li-c>n tre a tm e n t, o c u la r s i^ n t h a d d ra m a tic a lly re s o lve d i.b anti
and C j.T h e a n g i o g r a p h i c p a t t e r n is n o t h e l p f u l i n d i s t i n ­
F-i. This Ы -y e a r-o ld diabetic m ale presented w ith 1 v e a iV his-
g u is h in g m e ta s ta tic c a r c in o m a fr o m c h o ro id a l in filtra tio n
torv o f n a n o w vis io n in the ri^hl u y e . H e h a d harl unilateral
b y a n o n p ig m e n te d m e l a n o m a o r b y i n f l a m m a t o r y c e lls ."
iritis, a steroid h ya losis, a n d n o n p ro life ra tiv e d ia b e tic rietinop-
U ltr a s o n o g r a p h y o f le s io n s 3 m m o r h ig h e r m a y h e h e lp ­ altiy in I his e ye 2 years previcujjijy- There w e re several y e l­
fu l in d i f f e r e n t i a t i n g m e t a s t a t ic t u m o r s , w h i c h are u s u a lly lo w subretinal linear lesions in the po ste rio r p o le a n d areas
m o r e h i g h l y re fle c tive th a n m e la n o m a s . o f retinal p ig fn e n l ep ith e lia l a tro p h y in Lhe m id p e rip h e rv i C
a n d H i . E a rly -p h a s e flu oresce in anj^ioyram s h o w e d le o p a rd -
speJ p ig m e n t^ rt c h a n g e Lhal persists th ro u g h all p h ases o f the
a n g jo g ra m (I). A chest X -ra y re ve a le d m ild pleural e ffu s io n {Jf.
A t hesl c o m p u te d Lom ofjra ph ic scan revealetl m ediastina l
ly m p h a d e n o p a th y , tw o p u lm o n a ry n o d u le s , and pleural e ffu ­
sion (K and L.i. O p e n - lu n g b io p s y revu a lu d lym ph o i:y1e-ricl>
varia nt ty p e o f H o d g k in 's ly m p h o m a . Th e p le u ra l flu id s h o w e d
ly m p h o c y to s is . D ia g n o s tic v itre c to m y w as d e c lin e d by the
p a tie n l. The: p a lie n l w as started o n s y s le m if c h e m o th e ra p y for
Lhe Hctdj^kin'i ly m p h o m a , a n d his visual s ym p to m s a n d M|ins
im p ro v e d .
lA -f, iMini '!'li,L|j|jrj|.:Tbv 4;| , j L.- ' i,vilM ptfnYibiloTi; C —L , ииигГсзу □(
Lj r . C Ju .m L>. ‘ чu.u ;. L'ii ,in d L>r. .'i ihiri L 'h o i
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1 4 ,3 0 C h o r o r d a l m e ta s ta s is .

A-С : O c c u lt, s m a ll^ n o n p ijjm e n te d m e La s ta lic hreasL car­

c in o m a c a u s in g re tin a l d eta ch m e n t and b lu rre d visio n in л
2 & - y e a r - o j d v i r t ^ i a n w i t h a h i s t o r y (jf ( J i a s t e c E o m y a n d d u c t a l
ce ll t i i r d n t ] i n ;i . S l f i J E C ^ i s m f c a n ^ i - o ^ r j m s d a r t t i n & t r a j f i d [^vi-
d eh ofe o f a fo c a l c h o r o id a l ru m or w ith p in p o in t !"lu o n t ’ H c e i n
k ^ a k s o v e r l y i n g i<b s t J r f a G $ i n l h e j u K t a p a p i l l r t T y a r e a ' . В a n d О .
I.?—t j-: M u hi foca l m crfaslalit c a rc in o m a fro m I he? lunf^K s im ­
u la tin g lH - li Ic jKJHtoriur m u Hi focal p la c o id p ig m e n t e p ith e -
lio p a lh y ^ M P P E in а 3 3 -у ^ а м щ Й m a n . The p a liu n l w a s
a iia w q № of' the lu n g c a rc in o m a at lh e tim e h e w a s in itia lly
seen. A n g io g r a p h y , u n lik e that in A P .V l Ph’ E , s h o w e d n o e v i­
d e n c e o f o p a c ific a lio n o f th e ro lin a l p ig m e n t e p ith e liu m
fH F 'b 1 b u l d flly irregular d is ru p tio n o f lh e R P t .i n cl late tLa in -
in ^ (F a n d ( j ) .
H a n d I: This w o m a n w a s seen b e c a u s e o f ra p id loss o f
vis io n in b o th e yu s. 11 w a s c a u s e d by m e tasta tic Eiroast c a r­
c in o m a Lo the c h o r o id a n d h e m o r rh a g ic d e ta c h m e n t o f Lhe
relina n tvnLh ереь. A n ^ io ^ ra p h v s h e w e d e x te n s iv e le a ka g e
o f d ye fro m lh e I Lim a г surface that w k p a rtly o b s c u re d b y
lh e a ib re b n a ) b lo o d Mi.
|-L : T h is rn m a n e x p e rie n c e d b ila te ra l lo s s of visio n and
recent d e v e lo p m e n t of a n o d u le on ifie fo re h e a d (a rro w s ,
|i. T h e r e w a s b u llo u s d e t a c h m e n t o f th e re Lin a in fjo t h eyes
iК i o v r ^ l y i n ^ n tm p la m e n te d c h o ro id a l Ijm o fs . В i u p s o f th e
n o d u le on ih tj fo re h e a d re ve a le d m c 'L a s L a L ic b ta a s l c a rc i­
nom a. In a d fa tio n of b o th eyes caused p r o m p t fla tte n in g o f
th e m e ta s la lic 1u m o r, d is a p p e a ra n c e o f th e s u b re lin a l : In i d .
a n d re s to ra tio n o f v isio n (L). N o t e i n c r e a s e d m o t t l i n g o f I h e
F il'l: i n l h e a r e a o f l h e t u m o r a f t e r t r e a t m e n t .
 tfiffe rtm lia t d ia g n o s is in c lu d e s a m d a n o ttc n e v u s ., F 4 .3 1 C h o r o i d a I m e t a s t a s is.

am e la n o tic m a lig n a n t m eEanom a, E e u k e m ia , la rg e ce l!

A —F : А t)4 -y e a r-o ld w o r n a (i ttte s e rttm w ilh : d prCKnesiS.ivE
Lym phom a [re lic u tu m ce ll s a r c o m a ] , c h o r o i d a l o s te o m a .. гп а С м Ц г I « i o n in h e r left e y e . tie r pasl tp e d iC a l iiistoTy
c h o ro id a E h e m a n g io m a . c h o ro id a l n e o v a s c u la riza tio n w a s sign i fit :m l fo r b re a iL c A № № w iLh sp re ad to tw o аяИ-
w ilh o v e rty in g fo c a l e x u d a tiv e d e ta c h m e n t g ra n u lo m a s Iа ry ]yn .i|] h nod es sLage 11A , w h ic h w a t d ia g n u s e d I f i year^
such as sa rc o id o s is and tu b e rc u lo s is , and iu jtla p a p ilia ry p re v io u s ly a n d IneaLed w ilh a m o d ifie d radical n u s te c L o m y
e x o p h y tic c a p illa ry heEn a n g i o m a s a f lh e r e lin a .1 ■ ' W h jfc li fo llo w e d b y c h e m o th e ra p y . As- Ihe lu m en w a s eslTo^en a n d
p ro g e s te ro n e re c e p to r-p o silive ., La m o x ife n w a s p re s c rib e d for
L b e t u m o r is m u Eli f o c a l i n n a t u r e , t h e d i f f e r e n t ] d i a g n o ­
.j years ■ 11j : :rf 'liillc '.(4.U : ose lh..> ;J,I .'.i n - - -11 ->I ! h с i ■I i : 11
s is m a y i n c l u d e i n f l a m m a t o r y d i s e a s e s s u c h as a c u l e p o s ­
h a d b e e n ;n rem ission since. O n e y e a r a g o , she гю1 L'd
te rio r m u ltifo c a l p la c o id p ig m e n t e p ith e lio p a th y {Fig u re
b lu rre d v is io n in h e r left e y e (2Q/1 O O t. A p la c o id p a rtia lly
1 4 .3 U D and EJ. A th o ro u g h m e d ic a l h is to ry a n d e r a In a ­ a tlig la n o tic m a c u la r m ass w a s o b s e r v e d , w h ic h w as c o m in u -
tio n s h o u ld b e d o n e lo d e te rm in e (h e presen ce o r absence uus w ilh an e x I rand oral n o d u le B f lo w e r a c o u s tic re flo c liv -
o f a p rim a ry tu m o r, w h ic h in fe m a le s m ost Lre q u e n tlv ity thari lhal o l Lhe s u rro u n d in g o rb ita l tis to o . C i v t 'n lh e
o c c u rs in th e breast a n d in m a le s in Lhe i u n g . ' ^ in gen­
p a tie n t's h islu ry o f breast ta n e fi^ a rn etaslatic e v a lu a tio n w a s
p e rfo rm e d fA j. 5ca tiered ly tic b o n e tesions w e re d e le c te d
e ra l, m e ta s ta s is f r o n t b re a s t c a n c e r o c c u rs in t h e s e llin g o f
hy c o n ip jtu d to m o g ra p h y , a n d t l , le c h n e tiu m -^ ^ b o n e scan
a know n p rim a ry tu m o r while o c u la r p re s e n ta tio n m ay
re v e a le d m u lLiip k1 fo c i o f a b n o r m a l u p ta k e (Ifiji [ J u t 1 So Lhose
p r e c e d e t b e d i a g n o s i s ol" t h e p r i m a r y t u m o r i n t h e l u n g / ' fin d in g s , a b o n e m a r r o w b io p s y w a s p e r fo rm e d , w h ic h
In lhe absence o f d e te c ta b le p rim a ry tu m o r, fin e -n e e d le s h o w m a d e n o c a r c in o m a th a t w a s stro n g ly е Ь ЕШ й ег re t'c p lo r-
a s p ira tio n b io p s y o f th e c h o ro id a l tu m o r m ay be neces­ p o s Ltf№ . The paLienL w a s d ia g n o s e d w illi breasL c a n c e r m b -
sa ry to e s ta b lis h th e d ia g n o s is . X - r a y ir r a d ia tio n , h o r m o n a l slatic [ j b o n e a n d c h o ro id w ith [ran-sscleraE exLen-sion. A lle r
th e ra p y, a n d c h e m o th e ra p y m a y b e s u c c e s s fu l in c a u s in g b m o n th s o f IruaLm ent w ith a n a ro m a la se in h ib ilo r (anauLro-
z o t e 1 m g d a ily }, vis u a l a c u ity im p ro v e d to 2 0 / 4 0 I D a r d EJ.
re s o lu tio n o f lh e d e ta c h m e n t a n d re d u c in g tbe s ize o f th e
t h e m a c u la r lesion repressed w ith c o n c o m ita n t re s o lu tio n o f
c h o n o id a E L u m o r (l ig u ie L 4 .3 0 K and Ь } ь2 И 263 M e t a s t a t i c
lh e H ttra sc fe ra l c o m p o n e n l (F $
Lb y ro id c a rc in o m a m ay re s o lve fo llo w in g s y s te m ic |JLI
t h e r a p y . " Lis lro g e n and p ro g e ste ro n e re c e p to r-p o s itive L u n g m e ta s ta s is r e s p o n d in g to e r lo tin ib .

breast c a n c e r o fte n re s p o n d s lo o ra l a ro m a ta s e in h ib ito rs G - L : A 4 9 -y e a r-o E d n o n s m o k in g w o m a n n o te d a Eeft p a ra ­

ce n tra l s c o to m a . A s o lita ry c re a m y w h ite s lig h tly raised
s u c h a s a n a s t r a / o l e [ E - 'i g u r e l 4 . 3 L M o s t re c e n tly m e ta ­
lesion w ith o u t o v e rly in g s u b re tin a l flu id w a s seen In h e r
s ta tic a n d primary a d e n o c a r c in o m a o f th e lu n g h a s s h o w n
loft e v e Ci—11. V is u a l a c u ity w a s 2 0 .0 0 in each e v e . A sys­
re sp o n se to oral e rlo lin ib ( T a n c e v a )., a n e p i d e r m a l g r o w t h te m s w o r k u p re v e a le d a p rim a ry a d e rttjc a rc ln d m a o f the
fa c to r re c e p to r in h ib ito r p ro te in k in a s e in h ib ito r [l-'ig u re !d n g that w as c o n fi rm ud b y b io p s y . She re c e ive d oral e rlo -
1 4 .3 1 G - L ) . Linib (Ta rc e va J, a n e p id e rm a l g r o w th fa c to r re c e p to r in h ib ito r
p ro te in k in a s e in h ib ito r. T b e lesion p ro g re ss ive ly regressed
in ib ic ^ n e s i i| a n d К at й w e e k tl w ith c o m p le te fla tte n in g
o v e r 7 m o n lh s , a lo n g w iLh reg ression o f h e r lu n g mass; IL:-.
A u lo flu o re s c e n c e im a g in g s h o w e d p u n c ta te in c re a se d a u to ­
flu o re s c e n c e , e v e n e x te n d in g b e y o n d Lhe tu m o r d im e n s io n s ,
suggesting a c tiv ity in Ihe s u rr o u n d in g rulinal p ig m e n l e p ith e ­
liu m d u rin g lh e process o f regression :K .. S h e has m a in ta in e d
a v is io n o f 2 0 /2 0 w ith n o furl b u r s y m p to m s !ill d a te .

IA-I-. T imm W u ^ lis ljL .tl..-"■' wilh pt;nnJulH>.)

l i'i i’ai.'i Ini fAtim tatic Turners 1241
Metastatic Sarcoma 1 4 .3 2 L ip o s a r c o m a m e ta s ta s is to c h o r o i d , re tin a , a n d
v itre o u s .
S a r c o m a s ra re ly, if eveF, m e ta s ta s iz e l o th e eye, w it h o n ly
A -H : I his to 7-y e a r-o ld A fr ic a n A m e r iсa n w o m a J i p re s e n te d
s ix p r e v i o u s l y k n o w n cases in lh e lite r a tu r e , o n e e a c h f r o m
w ith pain tess g ra d u a l d e c re a se in vis io n in the lefl e ye Id
an a lv e o la r s o ft-p a r l s a r c o m a o f th e rig h t lo w e r e x tie jriity ,
2 0 /5 0 o v e r о m o n lb s . There w e re a fe w v ilfe o u s cells asso­
c o n g e n i t a l f i b r o s a r c o m a o f ( h e Lc fl l o w e r e x L r e m it y .. o s t e o ­
cia ted w ith a w h ite fib ro v a s c u lar p e d u n c u la le d m ass aris­
g e n ic s a r c o m a o f l h e le ft l o w e r e x t r e m it y , g a s tr o in te s tin a l in g fro m the retina an ti h a n g in g in Ihe vitre o u s c a v ity (A>.
stro m a l tu m o r, and E iw m g s a r c i ^ i o f tb e p e lv is a n d r ib . 5 he w a s a n a v id g a rd e n e r; a c lin ic a l d ia g n o s is d f p o s s ib ie
Th e p a tie n t w ith m e ta s ta tic lip o s a rc o m a to th e c h o r o id , ТЪкосага g ra n u lo m a w a s made?. h b silive serum Toxocara
re tin a r a n d v i t r e o u s if lu s t r a t e d i n fig u re 1 4 .j3 2 m im ic k e d liter and p e rip h e ra l b lo o d u tw in o p b ilia o f f l % c o iro b o ra L e d
the c lin ic a l d iagnosis,. S h e w a s a d v is e d oral a lb e n d a z o le
a n in Jla m m a to ry g r a n u l o m a , a n d w a s d ia g n o s e d b a s e d o n
a n d la p e iin g Systemic! slero ids fcx a m o n th . The? p a lie n l d id
c y to lo g y o f h e r v itre o u s flu id o b ta in e d at su rgery.
nert fill h e r p re s c rip tio n a n d re tu rn e d 5 ijia n lb s Saler w ith n o
a p p re c ia b le c h a n g e in s y m f>ton is . H e r vis io n h a d d e c neased
to 20 ^40 0 . Lhe w h ite m ass bud in cre a se d in s ize , a n d Ihe
p e d u n c le w a s m o re va s c u la r i li a n d C ) . U llra s o u n d s h o w e d a
solid mass w i lh a d ja c e n t tra cticn a E retinal d e ta c h m e n t ( D ) . A
1 1 -lum: i : i: \ iifft t d 'n i1 ,m d ,i b iu p -'- f -l 11■■■ i : . i-s v iilri'cd n \
a sm all p ie c e . T h e le s io n w a s лгиЬ1н?ту" a n d d itlic u ll to cul
in lo . V itre o u s flu id w a s sen I for c y to lo g y e x p e c tin g lo fin d
e o s in o p h ils , b u] re tu rn e d w illi p re s e n c e o f u n d iffe re n Li a Led.
a n a p la s tic cells w iLh m a rk e d Iv a ty p ic a l nu( lei a n d a high
n u c le a r-to -c y to p la s m ic ra tio tE J. 5 h e y a v e a h islo ry o l retro-
p e rilo n e a l sa rc o m a re q u irin g a n e p h re c lo m y 1 0 years p rio r.
fcnucleatJon o f lh e e y e c o n firm e d c b o rio ro lin o v itre a J m e ta s ­
tasis fro m Lhe rip o s a rc o m a . T h e tum or; C o n s is te d o f p le o m o r­
p h ic tu m o r cells a n d a b u n d a n t c o lla g e n I F - H ) . T h e cells b a d
a high n u c le a r -to -c v lo p la s m k : ra lio w ilh h y p e rc b ro m a tic
n u c le i a n d p r o m in e n t n u c le o li 1 Н к T b e c h o r o id c o n ta in e d a
th r o n ic in fla m m a to ry ce]J in fiitm le in tbe area s u iro u n c iin g
the m a s s . T b e retina d is p la y e d o u te r-la y e r a tro p h y a n d g liosis
o v e rly in g ]b e base o f the le s io n . T h e r e w a s n o e v id e n c e o f
scleral от o p tic n e rv e in v a s io n .
i h!г-1□г• :l; l г t \v :l h pwrtnhdifln M e h ta S. A&,irwjl Л ^ ’.
Leukemic Choroidopathy F 4 .3 3 M a c u la r d e ta c h m e n t c a u s e d b y le u k e m ic
in f r lt r a ( io n o f c h o r o id s
P o s tm o rte m eyes of p a tie n ts w it h le u k e m ia d e m o n s tra te
Л —C : C h o ro id a l lu n iu r rind serous d e la c h m e n t fif Ihe ШчэеиЗа
h is to p a th o lo g ic a lly a m ild le u k e m ic in filtra tio n o f th e
s e c o n d a ry to le u k e m ia in- -a 5?}-vear-old w h ils w o m a n w h o
u v e a l tra c t, b u t m ost do not show o p h lh a lm o s c o p ic e v i­
d & V c fo p e d b lu rre d v is io n anti m e la m o rp h o p H ia in I h o lefl
dence o f c h o ro id a l in v o lv e m e n t d u rin g life . In som e
e v e . N e a r I h o Le m p ora l m a rg in of th e left o p tic disc: Lhere w a s
p a tie n ts , how ever, th e in filtra te becom es s u ffic ie n tly a m o u n d -lik e e le v a tio n o f the c h o ro id a n d a s h a llo w serous
in te n se l o cause d a m a g e lo th e o v e r ly in g R P E a n d se rou s relinal d e ta c h m e n t lh a l e x te n d e d in lo Ih o m a c u la r reg ion
re tin a l d e t a c h m e n l . j4,6" j h 4 D e ta c h m e n t o f th e RPB m ay Ib la c k arrow s.. A ) . A sm all a m o u n l o f s u b re lin a l b lo o d ih la c k
a ls o o c c u r .-1 0 ' I t ie c l i n i c a l p i c t u r e m a y b e m i s t a k e n f o r c e n ­ a n d w h ile а щ № ) was p r e s e n t A n g io g r a p h y r e v e l e d m u lLi-
p !o , s m a ll, p in p o in t areas o f d iffu s io n o f d y e [ru m the su rfa ce
tra l s e ro u s c h o rio re tin o p a th y (N g u re L 4 .3 3 A J , o r in ih e
oE Ihe lu m o r as w e ll as e v id e n c e o f Eeakag^ o l d ye fro n t the
c a s e o f m o r e w i d e s p r e a d r e l i n a l d e t a c h m e n t , I E a r a d a 's d i s ­
o fЛ it: n e rv e c a p illa rie s in to ih e s u b re lin a l e x u d a te (fl a n d Q .
ease (fig u re s 14.33D and L and 1 4 .3 4 ) . H u o r e s c e in a n g i­ T h e pa Lien I w a s a d m ilLu d It) ih e h o s p ita l, a n d b o n e m a r r o w
o g r a p h y is u s e f u l in d e te c tin g th e areas o f K P li dam age e x a m in a tio n reveal t*d a cu Le m v e ln m o n o c Y tic le u k e m ia . T h e
u n d e r ly in g th e se ro u s d e t a c h m e n t {h ig u re s 1 4 .3 3 B , С and p a tie n t died s o o n afterward.
F and 1 4 .3 4 C ) . t h e s ite s o f le a k a g e o f d y e f r o m th e u n d e r ­ D -F : lij lateral hi i llous retinal d e la c h m e n L s im u la lin ^
ly in g c h o r o id are u s u a lly m u lt ip le p i n p o i n t areas s im ila r
FHaiada^s d ise ase in a 2 5 -y e a r-o ld p a tie n t w ith a c u te le u k e ­
m ia ILJ a n d E ). H is in ilia I m e d ic a l e v a lu a tio n re v e a le d le u ­
to th o s e seen in Harada's d ise a se and o th e r in filtra tiv e
k o p e n ia b u l n o e v id e n c e o f le u k e m ia . A n jjio ^ ra p -h y re v e a le d
d is e a s e s o f th e c h o r o i d . 'I h e c h o r o i d a l m filir a te m a y o c c a ­
m u ltip le foca l areas o f d y e leakage fro m the c h o r o id a n d
sio n a lly p rodu ce a lo c a lize d o r d iffu s e c h o ro id a l tu m o r
Eater a fla g sto n e p a tte rn o f s ta in in g b e n e a th th e retina I F ;.
L e u k e m ic tu m e fa c tio n s o f th e c h o r o id are m o r e fr e q u e n tly A lth o u g h Ihe c a u s e o f Ih e p e c u lia r o l k o l d p a tte rn o f late
a s s o c ia te d w ith a c u te L y m p h a t ic le u k e m ia . flu o re s c e in s ta in in g iK u n k n o w n . Its a p p e a ra n c e s o ^ e s ls I hat
O c c a s io n a lly , s trik in g le o p a r d -s p o t c h a n g e s m ay occur there w e re m u ltip le re la tive ly flat a re as o f d e ta c h m e n t o f the
in th e R Pt in p a tie n ts w it h e A t e n s iv e c h o r o i d a l in vo lv e ­ re lira l p ijjrn e n l e p ith e liu m 1ЫРЫ. w h ic h in ihis paLienL m a y
h a v e b e e n c a u s e d b y le u k e m ic in filtra tio n Iro m the c h o r o id
m e n t w ith le u k e m ia (fig u re s I4 .3 .3 t i-J a n d i 4 . 3 4 H , 1, K -
in lo ih e s u b -h iPE s p a c e . The relin a l d e ta c h m e n t d is a p p e a re d
a n d L ) , 2* ? ' 2 ™ ^ 71 И is l i k e l y t h e e x t e n s i v e R P t : n e c r o s i s a n d
а Пет corlico sSerojd Lrea Lm enl. H e d ie d , h o w e v e r, a b n u l f>
c l u m p i n g o f p i g m e n t t h a t o c c u r s i n t h e s e c a s e s is c a u s e d w e e k s latefj a n d a и Lops-у re v e a le d m y e lo g e n o u s le u k e m ia .
b y th e le u k e m ic in filtra tio n o f th e c h o rio c a p illa ris , c h e m o ­ i = - l : E*eculiar с lu m p in g o f Ihe p i^ m e n L e p il h e liu m in a
th e ra p y, o r a со m b i n a tio n o f b o th . ft-ye a r-o ld pa Lien I IneaLud for a c u te ly m p h o c y tic le u k e m ia . H e
The r e a d e r is r e f e r r e d to C h a p te r 13 fo r d is c u s s io n of h a d b e e n tre a te d w ilh viiv. ri stin e, p re d n is o n e , m elhcfl resa le,
re tin a l a n d v itr e o u s m a n ife s ta tio n s o f le u k e m ia a n d lar^e
arid c y c lo p h o s p h a m id e . H e d e v e lo p e d a lo p e c ia a n d severe
visual loss. T h e v is u a l 1(e s w as m o re n o tic e a b le at nij^hL Ihan
ce ll l y m p h o m a , w h i c h m a y c a u s e a v a r ie t y o f f u n d o s c o p i c
dllrtljlB 4he d a y . H e d ie d 3 m o n lh s later a n d h is lo p a lh o lo y ic
p ic tu re s th a t m a y s im u la te m e ta s ta tic c a r c in o m a , m u lt ip le
e x a m in a tio n re v e a le d m u I Li p ie c lu m p s o f R P E cells (a rro w i
e x u d a tiv e Е Р Ё d e ta c h m e n ts , m u lt if o c a l c h o r o id itis , re tin a l a n d m ild le u k e m ic i nfi ll га I i o n o f ih e c h o r o id . It is u n k n o w n
a rte ry o c c lu s io n , a n d a c u te re tin itis . w h e th e r Ihe cha ng es in lh e K P b w e re p rim a rily aLLrib u tab lo
to ijn o x ia s e c o n d a ry lo Lhe a n e m ia or le u k e m ic infiltration
o f the chork^capillari-s nr lo lh e lo xic e ffeels o f d ru y s ased in
Ih e ra p y. From d a y m a n el a I.- 1 ' p u b lish e d w ilh p e rm is ­
s io n fr o m lh e A m e ric a n l o u r n a l o f O p h t h a l m o l o g y ; G ib p y rig h t
by l h e O p h t h a l m i c P u b l i s h i n g Cfo.i
h4. H A c u t e m y e lo id l e u k e m ia tvilh le u k e m ia cu tis
b in u Iafit ug V o g t—K tiy a n n g i - H a r i d a d isea s e .

A —L : A 5 5 -y e a r-o ld le m a te o n Ire a tm e n t lo r a c u te m y e lo id
le u k e m ia d e v e lo p e d u n ila te ra l ra p id Loss o f v is io n In h e r
right e y e o v e r b d a ys Lo c o u n t [in h e re . T h e right lu n d u s
s h o w e d serous retinal d e la c h m e n l fn v o tv in g the p o s te rio r
p o le iA Lind B ). M u o r e tc e in а л ^ н и ^ гл т rtivtia lcd several p in ­
p o in t h y p e rflu o je s c e n t л геля Lhji L tanked d ye into I he? s u b -
retinal sp a ce I'-C I. O p t ic a l c o h e re n c e to m o g ra p h y d e le c te d
s e ve r;. I s e p U ц-.-Л h i n Ih e s ito lis ■:■!(■■.. 11: ■>n suj’ ftC’sLin^; hi^h
fib ril] conLeitl ;m d in a d d ilio n . sm all U P E d e t a c h m e n t
i|J l лпd i f ro w s ) a n d л I the ta rn s lim e she d e v e lo p e d
m u ltip le flu c tu a n t blisters o v e r h e r b o d y (Ek S h e w a s n e u tro ­
p e n ic w ilh □ w h ite L o u n l o f 0 .3 . T h e s k in lesions w e re d ia y -
nosed c lin ic a lly as le u k e m ia cu tis a n d sh e w a s c o n s id e re d lo
he ;n ■:-ih :I--:.- i:-,ii. d iv v iM '. l - 5 i : j | ш ih r le-нi-:л ^hovvee: 15i^i
i n f l i c t i n g the skin IF a n d C j . b h o ft ol n o t doini^ a n y th in g ,
she w n s skirted o n o r;il p re d fi isone G O m y л™1 y iv e n (te u p a -
^en I о im p ro v e hen w h ile jjq U n L Ten d a ys laler h e r vis io n
h a d im p ro v e d to 2 0 / 1 O Q , Lhe e xu d iLLive d e ta c h m e n t h a d
d ftJe a s fe d CH a n d J)r Ih e skin lesion s Ь е у л п lo d is a p p e a r a n d
h e r w h ile c o u n t im p rrjv o d . A b o n e m iirnow b io p s y d o n e л I
this lim e s h o w e d n o b lasts. Th e retina s h o w e d m ild p ig m e n ­
ta tion C o rre s p o n d in g lo the c h o r o id jl io b u le s fa rro w s , К .
w h ic h in c re a se d o vk ?t the n e \L visil a t S w e e k s . Th e fu n d u s
a u to flu o re s c e n c e g r a d u a lly in c re a se d , s u g g e stin g in g e stion o f
p ro te in fro m lh e su b retin a l flu id b y lh e геМплГ p ig m e n l e p i­
thelial c e lls , ^ iv in ^ il л Ie a p a rd -s p o t чзррелгалсе (I a n d L ) . A ll
skin lesion s d is a p p e a re d bv week?-.
Histiocytosis (Erdheim-Chester Disease) F4.35= C h o r o i d a l in v o lv e m e n t in E r d h e i m - C h e s t e r
d is e a s e (h istio c y to sis).
L r d h e inn - C h e s t e r d i s e a s e i s a r a r e , w i d e s p r e a d x a n t h o g r a n ­
A —I: A 3S-ycMLr-olcl fapd nose A m e jic-a n w ith а к п ш п d ia g n o ­
u l o m a t o u s in fittr a liv e d ise a se i n v o l v i n g t h e b o n e s a n d s o ft
sis cl" E rd h e in n -C lH ’ jLe f diseabo fo llo w in g л Ею п « b io p s y for
tissu e , l l i e e x a c t n a t u r e o f o r i g i n o f t h e d i s e a s e is p o o r l y
persihtont leg pain for ft ytM re pre se n te d w ilh b lu iru d vis io n in
u n d e rs to o d . W h e th e r it in itia lly m a n i tests in th e bone
his left eye? Гог 1 y e a r. M u llip le c re a m y p la c o id lesions asso­
m arrow and s p r e a d s ., o r o r i g i n a t e s in e x t r a m e d n l l a r y s ite s cia ted w ith inlra retin dl lip id e x u d a te *. w e re неел nl Lho le v e l
s im ila r to ly m p h o m a s is n o t k n o w n . H is to lo g ic a lly , i l is ot lh o (iio ro irl in ijo lh e y t's iA лиг! Li I. Q b t T t a l c o h e r e m .e
аипро-чх! ( ?J sIloct4- -H lO::.r.iy J : i^Lir:i.y.L'S .'.SSii:"j ::.1 L"l1 '.’.ill] to m o g ra p h y ot b o lh e ye s s h o w e d d iffu se c h o ro id a l th ic k e n ­
io u to n -ty p e g ia n t ce lls, ly m p h o c yte s , and p la s m a ce lls ing (C a n d □ ) . Flu o re s c e in a n g jo ^ ra m s h o w e d s ta in in g o l the
lesions b ila te ra lly a n d л p a rLly in v o lu te d L'h u ru id n l noov-iLscu-
Lh a t i n f i lt r a t e tb e s o f t tissu e . I h e d is e a s e a ffe c ls b o n e s , v is ­
hir теппЬтлгьо i£ ."N V M i in the left e y e (Ё - G , a ir o lv . Hurther
cera such as E i v e r . lu n g s, h e a rt, and su b c u ta n e o u s tissu e ,
w o rs e n in g Ы vision- Lo 2 (5 4 0 0 fro m serous fluid i H 1 o v e r i
lit la te r a l s y m m e t r i c a l o s t e o s c l e r o s i s o f t h e m e t a p h y s e a l a n d m o n lh s p r o m p te d a n in tra o c u la r in fec tion o f b e v a d z u m a b
d ia p h y s e a J re g io n s o f lo n g b o n e s is c o n s i d e r e d a c h a r a c ­ in his Iof I e y e w ith tu rth e r r-r^restion or Lho C N V M . H e
t e r i s t i c f e a t u r e . -7 - O p h t h a l m i c m a n i f e s t a t i o n s a r e r a r e ; t h e ru m iijn o d sliiblc o n s ys te m ic c o lc h ic in e n n d ojral sturoids ilj.
o rb it a n d p e r i o c u l a r tis s u e a r e ( h e E n o s t f r e q u e n t site s o f К ч 'и г С е ч у c jf L )r . N l .i I A l U . 't j j m . .

in v o lv e tn e n t.J ^ ■ ( J h o r o i d a l i n f i l t r a t i o n ( ] :i g u r e 1 4 . 3 5 ) i s
e x i r e m e l y r a r e . ' I'h e s e p a t i e n t s a r e d i a g n o s e d b a s e d o n s y s ­
t e m i c a s s o c i a t i o n a n d b i o p s y f r o m a s u i t a b l e site .
In filtr a tio n o f tb e c h o r o id w ith cream y y e llo w g ra n u lo ­
m a s m im ic s a c lin ic a l a p p e a ra n c e o f s a rc o id o s is . O r b i t a l
in vo lv e m e n t m im ic s th y ro id o rb ito p a th y and p s e u d o lu -
m o r o f th e o r b it. T re a tm e n t in vo lv e s th e use o f s y s te m ic
ste ro id s a n d im m u n o s u p p re s s iv e s .
 ЗЭ. Hlsx i. -Ana 5. Еесл. CttfTa <гкirailKlai отз зг м u’altrcmatos h OpKfrilnol
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 C h a p te r 15
Optic Nerve Diseases that may
Masquerade as Macular Diseases
D is e a se s th a t p rim a rily a ffe c t ih e o p tic nerve m a y occa- I > . I> 1 C o n g e n it a l p it o i th e o p tic d is c c a u s in g s e ro u s

s La n a lly in v o lv e s e c o n d a rily th e m a c u l a r area o r m ay be m a c u la r d e ta c h m e n t,

m is ta k e n fo r re tin a l d ise a se s, i o m e o f th e m o s t fr e q u e n t o f
A —D : Th is 2 7 - y e a r -o ld w o m a n c o m p la in e d c f b lu rre d v is io n
th e s e d ise a se s a re d is c u s s e d in th is c h a p te r. that flu c tu a te d in Lhe right e y e Гиг several w e e k s . Serous
d e ta c h m e n t o f Ih e re tin a e x te n d e d I d Lhe m a rg in o f Lhe
o p lic disc pi L I a rro w , Л a n d B l M o te subnetiniLic p re c ip i-
O P T IC D IS C A N O M A L IE S
Lales fo rm in g c o n c e rU ric lin e s o f ttem arcati|j|$ te m p o ra lly .
A S S O C IA T E D W IT H S E R O U S T h e d ia m e te r o f Lhe o p tic 1 disc w a s a b o u t Iw ic e IНлI o f Lhe
n o rm ill e y e . X e n o n p h o to c o a g u la lio n Wnis p la c e d alonj^ Lhe
D ET A C H M EN T O F THE M A C U L A te m p o ra l e d g e o f Ih e o p tic d is c as w e ll as in the o p tic p it

Serous d e ta c h m e n t of th e sensory re tin a m ay occur in

IT-'!'. S e v e n m o n th s laLer Ihe d o ta c h m e n l h a d noL r e s o k e d . 'Six
a n d o n e -h a ft y u a n , la te r lh e pa Lien I re lu m e d w ilh a p p r o x i­
a s s o c ia tio n w ith one o r a c o m b in a tio n o f d e v e lo p m e n ­
m a te ly 2 ^ 2 GO v is io n in lh e r i hi e y e . There w as n o lo n g E i
tal a n o m a l i e s o f t h e o p t i c nerve h e a d , '['h is s p e c t r u m o f
a n y serous d e la c h m e n t o f lh e m n c u la ( □ ) .
a n o m a lie s in c lu d e s p it, c o lo b o m a . m o rn in g g lo ry d e fo r­ E : Lo n jj-s la n d in g la rg e Serous retinal d e ta c h m e n t associaLed
m ity , a n d ju *ta p a p illa r y s ta p h y lo m a . w iLh an- o p tic p it. T h e re w a s y e llo w ек и d a le o n ihffc p o s te rio r
surface o f the d e ta c h e d re tin a c e n tra lly.
F —r l : This 2 9 -y e a r -o ld w o m a n , w h o W as k n o w n Lo h a ve a n
C O N G E N IT A L PIT O F T H E O P T IC o p tic p it a n d n o rm a l vis u a l fu n c tio n in the right e y e s in c e
D IS C A N D S E R O U S D E T A C H M E N T 10 years o f a j'e , p resen le d w ith a 4 -m o n lh history o f b lu rre d
v is io n in Lhe righl e y e . V is u a l a c u ity w a s 2CW50- T h e re w a s
O F THE M A C U LA a m o u n d -iik e e J e ta lio n o f lh e in n e r retinal s u rfa c e u r r o w -
heads.1 that e x le n d e d fro m Ihe o p 1 k : pal lh n o u g h o u l lhe m a c ­
U s u a l l y b e tw e e n t h e a g es o f 2 0 a n d 4 0 years, p a tie n ts w iL h
u la r a rea. T h e r e was a s m a lle r s h a rp ly c irc u m s c rib e d z o n e
c o n g e n ita l p it o f th e o p tic n e rv e h e a d m a y d e v e lo p s e ro u s o f w h a t a p p e a re d lo Ew d e la c h m e n t o f lh e геИ паГ re c e p lo rs
d e ta c h m e n t o f th e m a c u la (fig u re s I Ei. 0 3 - 1 F> . 0 3 ) . L_ 1,1' T h e fro m lh e p ig m e n t e p i!h e liu m M ir o w s , F) *h a l d id noL e x te n d
d e t a c h m e n t u s u a l l y e x t e n d s in a t e a r d r o p f a s h i o n (Fig u re to Lhe opLic p il. T h e p a tie n t c o u ld see a 5 0 -^ m k ry p to n re d
1 5 .0 1 Л . I - К) fro m th e d is c m a r g i n in th e v ic in ity o f th e laser .lim in g b e a m ih ro u g h o u l the a re a o f in n e r retinal e le v a ­
o p tic p it, w h ic h i n m o s t c a s e s is l o c a t e d a lo n g Lhe t e m ­ tion^ in c lu d in g Lhe ce n tra l area ol relinal d e ta c h m e n Lr b o th
b e fo re a n d e v e n a fte r p la c e m e n l o f Lw o ro w s o f k iy p lo n re d
poral m a rg in o f th e o p tic d isc . P its a n d d e ta c h m e n t are
p h o lo c o a g u la tio n s a lo n g Lhe te m p o ra l e d g e o f the o p tic p it.
uncom m on at th e n a s a l .m a r g in o f th e o p t i c d is c (Fig u re
S e ve n m o n th s later Ihe e le v a tio n o f lh e in n e r retinal su rfa ce
1 5 .0 2 Л - С ) . T h e o p t ic d isc d ia m e te r i n th e a f f e c t e d e y e is
a n d retinal d e ta c h m e n t w e r e n o lo n g e r p resen l. There w a s
u s u a lly la rg e r th a n in t h e u n a ffe c te d e y e .- , , J - A n o p tic p it a p a tte rn o f ra d ia tin g lines re s e m b lin g lo v e o m a c u la r schisis
m ay occur b ila te ra lly in 10 -15 % o f cases and m ay be c e n tra lly ( C l . T w e n ty -s ix m o n th s a lte r tre a tm e n l h u t vis u a l
in h e rite d as an a u to so m a I-d o m in a n t a b n o r m a l i t y ' 4 ' 11 a c u ily w a s 2 0 /2 □ a.nd th e m a c a la a p jrc a re d n o rm a l ( H ) .
P its m a y b e a s s o c ia te d w ith a c o l o h o m a o f th e o p tic n e rv e I - M : A 1 7 -y e a r -o ld A fr ic a n A m e r ic a n girl w ith d e c re a se d
vis io n m her lell e y e for -t years to c o u n tin g fingers. A central
head, and d e ta ils o f th e p it m ay be d iffic u lt or im p o s ­
sell is is-1ike d efect wiith s u *ro u n d in g suETneLinal tlu id a n d pne-
s ib le lo id e n tify [Fig u re 1 5 .0 2 1 1 and ]J. Som e p a tie n ts
cipiLales iK seen in Ihe letl m a c u la e m a n a Lin g fro m a te m p o ra l
w ith severe c o l o b o m a l o u s m a l f o r m a t i o n o f th e o p t ic d is c o p f i t disc pi I ilf | ..T h e pjt re m a in s n o n flu o re s c e n l d u e to c a p ­
m a y d e v e l o p e M e n s i v e r e tin a l d e t a c h m e n t [se e d is c u s s io n illa ry n o n p e rfu s io n . the cenLra] schisis s h o w s m o ll led h vp e r-
b e lo w ). O p tic p its lo c a te d in (h e c e n te r o f th e o p tic d is c flu o re s c e n c e , arid d ye leaks inLo lh e s u b rm in a l s p a c e on Lhe
are n o t a s s o c ia te d w i t h m a c u l a r d e t a c h m e n t . I'lie o p t i c p i t a n g io g ra m tK . The schisis c a v ity larrow presenl in the central
ts o f t e n c o v e r e d w i t h a g r a y m e m b r a n e t h a t f r e q u e n t l y h a s m a c u la , a n d a lull Ih ic in e s s delect ''a r ro w ■at the disc edi^e is
d e m o n s tra te d o n o p tic a l c o h e re n c e Io m o g ra p h y I M | .
one o r m ore h o le s w i t h i n it, p a r t i c u l a r l y in p a tie n ts w ith
m a c u l a r d e ta c h m e rits . M o s t a u t h o r s agree th a t th e r e t y p i ­ iA - t rru m tj.is f. 1 - M , r i i i i r l L ' i y j : f U r. k n n .rih .iH W illi.h m '- .-

c a l l y is n o p o s t e r i o r v i t r e o u s d e t a c h m e n t in e y e s w i t h a p iL
a n d s e ro u s d e t a c h m e n t o f th e m a c u la .'1 1 Sl O c c a s i o n a l l y ,
c o n d e n s e d v itre o u s stra n ds m a y e x te n d fr o m th e su rfa c e o f
[h e o p tic p it in to th e a n te rio r v itre o u s [F ig u re 1 5 . 0 1 M ) . En o p t ic p i L 'th e r e h a s b e e n no s a tis fa c to ry a n a t o m i c e x p la ­
s o m e p a tie n ts a c lo u d y p re c ip ita te m a y o c c u r o n th e p o s te ­ n a tio n fo r th is p e c u lia r c o n f i g u r a t i o n o f re tin a l e le v a tio n
r i o r s u r f a c e o f t h e d e t a c h e d r e t i n a ( F i g u r e 1 5 . 0 1 A , 1, a n d | } . seen b io m ic r o s c o p ic a lly in th es e p a tie n ts . W i l h p r o l o n g e d
W hen th is o c c u rs , t h e a re a o f d e t a c h m e n t m a y b e m i s d ia g ­ re tin a l d e ta c h m e n t, d e p ig m e n ta t io n o f th e re lin a l p ig m e n t
n o s e d as a s o l i d t u m o r ( F i g u r e 1 5 .0 3 C a n d Som e e p ith e liu m (I? I 3Li) occu rs in Lhe area o f th e d e ta c h m e n t
p a tie n ts d e v e lo p a c e n tra l area o f s h a r p ly d e fin e d re tin a l (F ig u r e s 1 5 .0 1 К a n d 35 . 0 3 A a n d l i j . C y s t i c r e t i n a l d e g e n e r ­
d e ta c h m e n t W ith a s u rro u n d in g la rg e r, le s s w e l l - d e f i n e d a t io n , s c h is is -lik e a p p e a r a n c e , m a r k e d t h i n n i n g o f th e fo v e -
area o f e le v a tio n o f th e in n e r re tin a l s u rfa c e , s u g g e s tin g o la r p o r t io n o f th e re tin a r a n d ra re ly fu ll-th ic k tie s s m a c u la r
[ h e p r e s e n c e o f r e t i n o s c h i s i s { F i g u r e 1 5 . 0 E I - L ) . JQi2! U n l i k e h o le a n d r h e g m a lo g e n o u s re tin a l d e t a c h m e n t m a y o c c u r
r e t i n o s c h i s i s . h o w e v e r t h e r e is n o t c o m p l e t e l o s s o f r e t i n a l (Fig u re 1 5 . 0 2 [ ? ) . ' ' л у ' 1 ''' S u b re tin a l n e o v a s c u la riza tio n
fu n c tio n in l h e area o f p s e u d o s c h is is in p a tie n ts w ith an m a y arise n e a r th e o p t i c p i t .'1 1'
 In p a tie n ls w ith a recent onset o f m a c u Ear d e ta c h ­ 1 5 .0 2 C o n g e n it a l p it a n d ju x ta p a p illa iy c o E o b o m a o l

m e n t, a n g io g ra p h y sh o w s n o a b n o r m a litie s in th e m a c u ­ th e o p tic d is o

la r a r e a .'1 ] 1 En e a rly-p h a s e a n g io g ra m s Lhe p it appears

A - D : A с о п р е л i la I p it in lh e пазл I part o f the n e rv e head
h y p o flu o re sc e n t (fig u r e 1 5 .0 1 k ) . Jn Lite r phases, hi m o s t caused a serous retinal d e la c h m e n l : a rro w s I na sallv lA'i I Ьл I
p a tie n ts , th e re is e v i d e n c e o f s ta in in g in t h e a r e a o f" t h e s u b s e q u e n t lv sp re ad tcj the m a c u la r a re a iB a n d О in lhis
p it w i t h n o e v id e n c e o f p e r fu s io n o f d y e in to th e s u b re ti­ b o y. A m id -p h a s e a n ^ io ^ ra m s h o w e d m a rk e d h v p e rflu o re s -
n a l flu id . A b s e n c e a f s ta in in g o f th e p it h a s b e e n a s s o c i­ c c n c e wilhiin lh e pit (a rro w s , L H .

a te d w i t h a b s e n c e o f re tin a ! d e t a c h m e n t recent m a c u la r
E a r d F: Serou s d e ta c h m e n t of lh e m a c tiFa a n d m a c u la r h o le
s e c o n d a ry lo я conj^enila ] pil La rro w , L'1 o f I b e o p tic n e rv e
d e ta c h m e n l, and no c ilio re tin a l a rte rie s e m a n a t i n g fro m
in a Э У-уо л гч > Ы w o rtia n w ith a 2 -m u rrth jh'Jslory (if b lu rre d
th e p it ." S ta in in g o f th e su b re tin a l flu id o c c a s io n a lly
vis io n in lh e ri^ h l e y e . V is u a l acuiLy in the rijjhl e y e w a s
o c c u r s ( i'ig u r e 1 5 .0 ] К J .' 1’ a l i e n l s w i t h loss o f p i g m e n t in 2 0 / 2 0 0 . И ш к й Ы а П a n y io y r a p h y s h o w e d e v id e n c e erf d p fH g -
th e R L 3IL c a u s e d by p ro lo n g e d re tin a l d e ta c h m e rit show m enlaticwi o l Ih e retinal p ig m e n l e p ilh e liu m ^arrow s, l-i in the
h y p e rflu o re s c e n c e c o rre s p o n d in g w it h t h e areas o f d e p i g ­ area d lh e serous d e la r.fm ie n l. h o l e lh e m o lllc d -E ra c k g ro u n d
m e n ta tio n d u r in g th e e a rly p h a s e s o f a n g io g r a p h y { f i g u r e Eiyp e fflilw ie scB n e e a p p a re n l in the лгал o f the m a c u la r hoEe.
This a n ^ io ^ ra m suty^ests lh e p ro tia Eiilily lh al lE>e serous
1 5 . 0 I K ) . 1" J h i s is o f t e n s e e n i n ( h e p a p i l L o m a c u l a r b u n d l e
d e La c h m e n l o f lh e ri^ h l т а щ а h u d b e e n pnesenl m u c h lo n ­
r e g i o n a d j a c e n t t o t h e o p Lie d i s c t n p a t i e n t s w i t h no p re­
ger th a n 1 m H fith s
v io u s h is to ry o f m a c u la r d e ta c h m e n t. A n g io g r a p h y s h o w s
G - l l l h i 1 .‘з-y e a r-o ld b o y w ilh л large o p lic d is c pil d e v e l­
n o e v id e n c e o f e ith e r c h o r o id a l o r re tin a l c a p illa ry p e r m e ­ o p e d a p e c u lia r viteiritonm d eposiL in the s u b re lin a l s p a ce
a b ilit y a lte r a tio n s . I h e fa iEu re to d e m o n s t r a t e a n g i o g r a p h i- o v e r a 6-m cm Lh p e rio d { C a n d H f . H e h a d a p o s itiv e sco-
c a lly e ith e r re tin a !! o r c h o ro id a l p e rm e a b ility a lte ra tio n s Lo m a , Ьи1 H is vis u a l a c u ily w a s 2 0 /2 0 o n bcuh o c c a s io n s .
tn th e presence o f a serou s m a c u la r d e ta c h m e n t s h o u ld T h e re w a s e a rly m e ttle d EiyperfludTeadeiC te c e n tra lly a n d late
K la in in ^ o f the pil (I).
a lw a y s a le r t th e c l i n i c i a n Lo th e p o s s i b i l i t y o f a n o p t i c p i t
j: C o lo E io m a w ilh Ad o u L)ie d isc" d e lo rm ilv in a 5 -y e a r-o ld ,
or a m o re p e rip h e ra l le s io n to account fo r th e d e ta c h ­
o th e rw is e n o r m a l, c h ild .
m e n t. O p tic a l coherence to m o g ra p h y ( O C E 'J th ro u g h th e
К a n d L: M o r n in g ^ lo r y d e fo rm ity erf lh e ri^hl o p tic n e rv e
p it shows th e d e fe c t, and a n y c o m т и п t e a Li o n w iLh th e a n d e x te n s iv e relin a l d e ta c h m e n t in the rig h t e y e IК j lhal
v itre o u s a n d / o r th e s u b a ra c h n o id space (Fig u re 1 5 .0 L M ) . d e v e lo p e d in a 2 1 -y e a r-o ld w o m a n n o te d to h a v e the o p tic
О С ] ' th ro u g h th e m a c u la c a n s h o w e ith e r a se ro u s re tin a l disc d u io r m ity since а ^ с b years. H e r vis u a l a c u ilv w a s lin g e r
d e ta c h m e n t (fig u re ] 5 .0 3 f 3 a n d J) o r a sc h isis or b o th c o u m in ^ o n ly in the rij^hl eyie. T h e гс Я тл w a s № atta'ched fo l­
lo w in g a v itre c to m y ^L). There w a s n o relin a l h ttle , a n d lh e
[F ig u r e s 1 5 .0 ] L a n d 1 5 :0 3 1 ]
s o u rc e o f Hie s u b re tin a l flu id p r e s u m a b ly w a s v ia a p il-lik e
P re s e n tly th e re is l i m i t e d in fo rm a tio n c o n c e rn in g th e
d e fo r m i1y h id d e n w ith in the disc a n o m a ly .
n a tu ra l cou rse o f eyes w it h an o p tic p it b e fo re o r a fte r
d e v e lo p m e n t o f serous m a c u la r d e t a c h m e n l.' " It i s
p ro b a b le th a t o n ly a s m a ll p e rc e n ta g e oE" e y e s w i l h a p it o r Lbe v it r e o u s ( H g u r e l 5 . 0 3 K ) . ,,,h C h a n g a n d a s s o c i a t e s
e ver d e v e lo p serous re tin a l d e t a c h m e n t . S p o n t a n e o u s re­ re p o rte d m e lriia m id c c is te rn o g ra p h ic e v id e n c e of com ­
a tta c h m e n t o f th e m a c u la occu rs in 3 5 % or m ore o f m u n ic a t io n o f th e s u b re tin a E a n d s u b a r a c h n o id spaces in
p a tie n ts w ith o p t i c p i t s . ” 1,1 11 12 W i t h a p ro lo n g e d d e la y in a c h ild w ilh a c o lo h o m a to u s m a lfo rm a tio n o f (h e o p tic
tea Lla c h m e n l , c ystic d e g e n e r a t i o n a n d p a r t ia l- o r f u l l - t h i c k ­ nerve and e xte n s ive re tin a l d e la c h m e n L. O th e r s tu d ie s
ness h o le f o r m a t i o n m a y o c c u r .1 Lo n g -te rm fo llo w -u p o f in v o lv in g ra d io is o to p e c i s t e r n o g r a p h y 1' and in lra lh e c a l
u n t r e a t e d e y e s su g g e sts t h a t in a p p r o x i m a t e l y 5 0 - 7 5 % of f h j o r e s c e i n r lfl a s w e l l as a tte m p ts to d is p la c e su b re tin a l
eyes th e v is u a l a c u ity W ill be re d u c e d lo 20/Ю 0 o r ivo re e flu id in to Lhe s u b a r a c h n o id s p a c e b y e le v a tin g t h e in lr a -
w i l h i n 5 - У y e a i b 5 rJt o c u i a r p r e s s u r e . 1' h a ve fa ile d to d e m o n s t r a te e vid e n c e o f
I-L i s t o p a t h o l o g i c a l l y , a n o p l i c p i t c o n s i s t s o f h e r n i a t i o n d ire c t c o m m u n ic a tio n b e tw e e n th e s u b a ra c h n o id space
o f d y s p la s tic re tin a i n t o a c o lla g e n -lin e d p o c k e t e x te n d in g a n d s u b re tin a l space. O n e p a tie n t w ilh a n o p lic p it e x p e ­
p o s te rio rly t h r o u g h a d e fe c t in th e l a m i n a c rib ro s a i n t o (h e rie n c e d Lw o e p is o d e s o f in c re a s e d in tra c ra n ia l p ressure
s u b a ra c h n o id space [lig u r e 1 5 .0 3 С a n d L>). c a u s e d b y p s e u d o l u m o r c e re b ri w i t h o u t d e v e lo p in g a re ti­
T h e p a th o g e n e s is o f th e d e t a c h m e n l a p p e a rs to in v o lv e n a l d e t a c h m e n t . 1 ’ D i r e c t c o m т и п tea l i o n b e t w e e n t h e v i t ­
Lhe p a ssa g e o f flu id fr o m th e area o f Lhe p i t i n t o t h e s u b - re o u s c a vity a n d s u b r e tin a l space v ia th e o p lic p it h a s b e e n
re tin a l space. I h e fa ilu re o f in tr a v a s c u la r flu o re s c e in l o d if­ d e m o n s tra te d in c o llie d o g s ( f ig u r e 1 5 . 0 3 L ) . :' J h i s c o m ­
fu s e i n t o Lhe s u b r e lin a l flu id in a ll b u l a fe w cases su g g e sts m u n ic a tio n c o u ld n o l be d e m o n s tra te d tn a hum an eye
t h a t it is d e r i v e d fro m e ith e r th e c e re b ro s p in a l flu id ' w i t h a n o p t i c p i t . ' 1'1
 I n g e n e ra l, a tte m p ts t o clo se th e n e c k o f lh e d e ta c h E n e n t a t f C o n g e n ita l p it o f th e o p tic dcscL

Lh e m a r g in o f lh e o p lic d isc w i t h p h o t o c o a g u l a i i o n , as w d d
A - С : in 1 9 7 .1} Ibis 2 1 -ye ar-cd d п и п presented w ilh b lu rre d
as p h o t o c o a g u l a t i o n o f t h e o p l i c p i l it s e lf, h a v e b e e n u n s u c ­ vis io n in Lhe rij]hl e y e caused Ejv ser-nuS m a c u la r detacfii£
ce ss ful in c a u s i n g p r o m p t r e s o l u t i o n o f lh e m a c u l a r d e t a c h ­ m e n ! (a n a w s r A l associaLud w iLh a n o ra E p il o l j b e o p tic d is c .
m e n t (E n u r e s p 0 1 A - C С . , n in d t l a t i d 1 5 . ( J 3 t ; - l } . H is v is u a l a c u ity was. 20 /70 . N o t e in the s le re o a rg io g ra m
Several a u th o rs have re p o rte d re s o lu tio n t h a t m a y re q u ire iB L a n d 33-R|i Ihe fo c a l th in n in g o f Lhe re tin a a n d a tte n u a ­
s e v e r a l m o n t h s o r l o n g e r a f t e r p h o t o c o a g u l a t i o n . '■ '*'■ ‘ 5 j l r , ' " !
tion o f 1 hr1 r h in a l p ig jn e n l o p i I h e liu m al Ihe Te m p o ral m a r­
gin o f Ihe o p tic d is c . T h e retina re a tta c h e d s p o n ta n e o u s ly
K e d e la c h m e n t n ta y o ccu r weeks or m o n th s I s t e E 35^ 8 ]Tie
w ith in s tY tra il years, a n d Й years later his vis u a l a c u ity w a s
absence o f p o s te rio r vitre o u s R e p a ra tio n in p a tie n ts w ith
2 0 /3 0 . T h e re a re ra d ia tin g p u ric e n lra l retinal fo ld s s jm u la lin g
m a c u la r d e t a c h m e n t b u r s t s th a t ira c tio n o f th e fo r m e d vil-
Ji-lin k e d uchisi-i tC .
re o u s in th es e p a tie n ts o n lh e a n t e r io r su rfa ce o f th e r e tin a D iin d E : H is fo p a L h o lo g y o f sent j u s d e ta c h m e n t o f lh e retina
L h r o u g h o u i th e m a c u l a r area m a y b e i m p o r t a n t in c a u s in g in a 2 1)-■year-old W o m a H iIh a n o p tic disc p i t Th e e y e Ш
th e p a s s ive m o v e m e n t o f e ith e r flu id v itr e o u s o r o f c e r e b r o ­ e n u c le a te d b e c a u s e o f a m is d ta ^ n o s is o f a c h o ro id a l n ie la -
s p i n a l flu i d d i r o u g h a d e fe c t w i t h i n o r a l th e m a r g i n o f the
n o m a , p re s u m a b ly c a u s e d by s o m e o p a c ific a tio n o f lh e s u b -
nil in a I ! !u id. S o to th e c y tLic d e g e n e ra lio n o f the d e ta c h e d
o p tic p it in to th e s u b ie tin a l space, i n o ld e r p a tie n ts w h o s e
relina '.a rro w , D : . t s h o w s d e ta ils o t lh e p iLf in d ic a tin g th re e
p o s te rio r vitre o u s is e xte n s ive ly liq u e fie d fu ll-Lh ie k n e s s
possib le routes Ety w h ic h flu id fro m the vitre o u s fv
h o le s in th e m a c u la a n d e ls e w h e re in th e p o s te rio r fu n d u s or Lhe s u b a ra c h n o id s p a c e ss' m ig h t pass in to Lhe suhretr-
do n o l cause re tin a l d e t a c h m e n t in th e absence o f b io m i- nal sp a ce >:srsi. rh e n e u ro e c to d e rm a l p o d itrfi of the pil :n j is
c r o s c o p ic e v id e n c e o f fo c a l v itr e o u s tr a c t io n . S o m e a u th o rs separated fro m its s u rro u n d in g fib ro u s c a p s u le ifl Eiy a m u ILi-
h a v e r e p o r t e d su cce ssful r e a l l a c h m e n l o f t h e m a c u l a u s i n g lo c u la Le d sp a ce Is).
a c o m b i n a t i o n o f o n e o r m o r e o f th e fo llo w in g : pars p la n a F : r h o lo m ic r o g r a p h o f opLic p iL in c o llie d o g . A r ro w s in d i­
cate c o in m u n ic a lio n o f v ilre o u s c a viLy w ilh s-ubrelinal красе.
vlfte c to m y , in lra v itre a l gas ta m p o n a d e , and p h o lo c o a g u -
G —I: Th is lfl-y e a r -o ld n o te d d e c re a se in v is io n in his (eft
L a t i o n . ' * - 5,31', л ■ .M o te c h n iq u e o f tie a tm e n t has grave d
e y e to 2 0 /4 0 0 fo r 4 m u n lh s . H ie rijjhl e ye w as n o rm a ] w i lh
u n i f o r m l y s u c c e s s fu l in p e r m a n e n t l y r e a t t a c h i n g Lhe r e t i n a .
2 0 /2 0 v is io n . A te m p o ra l o p tic d is c p i L w ith a d a ja c s n l serous
O c a s s io n a lly gas a n d / o r e m u ls ifie d s ilic o n e o il ca n m ig ra te detachm -unl a n d subnefinaj p re c ip ita te s is seen i C j . Th e
th ro u g h Lhe p it i n l r a c r a n La I l y . Ih is is e s p e c i a l l y lik e ly lo pationL h a d u n d e rg o n e laser (a rro w ] to lh e te m p o ra l edj^e
o c c u r w h e n t h e g a s b u b b l e is s m a l l e r ( b a n t h e s i z e o f t h e p i t of lh e d is c 4 m o n lh s p re v io u s ly w ith n o e v id e n c e o f flu id
or when L h e i n t r a o c u l a r p r e s s u r e is l o o h i g h . A re a s o n a b le
re s o rp Lio n . O p Iic a J c o h e re n c e to m o g ra p h y s h o w e d su b reLi-
nal flu id b e g in n in g lie v o n d lh e laser scar siLe I a rro w ) a n d
r e c o m m e n d a t i o n is o b s e r v a t i o n f o r a L l e a s t a m o n t h a f t e r t h e
e x te n d in g Lo the m a c u L i ( H a n d ]J.
o n s e t o f d e ta c h m e n t; if n o im p r o v e m e n t in th e d e ta c h m e n L
I- L: This 2 I - y e a r - o k l w o m a n w a s v is u a lly a s v m p L o m a tic a n d
o c c u rs , p h o to c o a g u la t io n across th e n e c k o f th e d e ta c h m e n t; c o rre c ta b le lo 2 0 /2 0 v is io n in b o th e y e s. !ihe g a ve a histoTy
i f n o r e s p o n s e o c c u r s vtfitbfltrt 6 - 8 x v e e k s , r e p e a t t h e l a s e r t r e a t ­ ot c o n s ta n t h e a d a c h e s 2 years p re v io u s ly LhaL w a s d ia g n o s e d
m e n t ; i f still n o i m p r o v e m e n t i n the d e t a c h m e n t , c o n s i d e r as p s e Lid o Lu m o r C e re b ri. T h e rigbL o p lic n e rv e w as n o rm a l:
in lra v itre a l gas t a m p o n a d e w i l h o r W i t h o u t p a n ; p la n a v itre c ­ Lhe lefL s h o w e d a d e e p c u p w ith a te m p o ra l p i L. N o m a c u la r
t o m y . U s e o f i n l r a v i t r e a l Lissel t i s s u e g l u e t o c o v e r t h e p i t h a s d e ta c h m e n t w a s p re s e n i.

been r e p o r t e d . rl"he , i u t h o r h a s u s e d tis s e l s u c c e s s f u l l y i n а I t Гшгп k ' r r y i ■Ms I, A m i r lc u ii M e d i c » l A la b C i n l l p h Ml i i jjh ls

f ^ s t l V e d . LJ h u m Ci."ibV": L fnnm ЙМйуп ' I 97*J. A n n c f It мп ,il
p a t i e n t w i t h t w o p r e v i o u s v i t r e c L o m y fa ilu r e s . Lise o f p r o p b y -
Asux ,i I h jii. All г цЫк H^t;rv^;rl i !.. (4iurlc;№ uf !>r. Kiul Slblnber^.l
E a c t ic t r e a L m e n l e i d i e r a d j a c e n t t o t h e p i t o r a s a c o a r s e s c a t t e r
p a t t e r n o f laser in t h e m a c u l a i o p r e v e n t d e t a c h m e n l m i g h t
b e c o n s id e r e d in t h e rare p a t i e n t w i t h a s t r o n g f a m i l y h is to r y 1 m ore o c c a s io n s of a fla m e -s h a p e d h e m o rrh a ge o il th e
o f d e ta c h m e n t a sso c ia te d w i t h o p tic n e rve p it, a n d p a rtic u ­ o p tic d isc . Jh e ty p ic a l fie ld d e fe c t in n o rm o le n s iv e eyes

l a r l y i n t h e s e c o n d e y e i f L h e lir& t e y e h a s p e r m a n e n t L o s s o f e xte n d s fro m she b lin d s p o t lo n ea r fixa tio n in a p is to l­

a m i t y f r o n t th is c o m p l i c a t i o n . s h a p e d с о n f i g u r a t i o n a n d h as a steep c e n tra l m a r g i n .
Jie c au se p a tie n ts w i t h a c q u ire d p its a n d w i l h l o w - l e n s i o n
g la u c o m a h a v e s ig n ific a n t ly g re a te r a m o u n t s o f fie ld lo ss
ACQUIRED PITS OF THE OPTIC th a n th ose w ith e le v a t e d i n t r a o c u l a r p re s s u re w i l h o u l piLs.

NERVE i t es p r o b a b l e t h a t o p l i c n e r v e s p r e d i s p o s e d l o d e v e l o p i n g
p its are m ore s u s c e p tib le lo dam age fro m th e d a m a g in g
Pit-5 ik e c h a n g e s in th e o p lic n e r v e b e a d m a y be a c q u ire d effe cLs o f i n t r a o c u l a r p r e s s u r e . W h e r e a s t h e r e a re s t r u c t u r a l
and m ay be lh e cause o f u n e x p la in e d lo ss o f paracen­ d iffe re n c e s in th e la m in a c rib ro s a in p a tie n ts w ith and
tra l a n d o c c a s io n a lly ce n Lral v is u a l fie ld lo ss. L 'b e s e p its w ith o u t lo w -le n s io n g l a u c o m a , 1^ th e p a th o g e n e s is o f th e
ty p ic a lly d e v e lo p in th e in fe ro te m p o ra i quadrant in a c q u i r e d p i l o f t h e o p t i c d i s c is s t i l l n o l c l e a r . u l H is p o s t u ­
o ld e r p a tie n ts w ith norm al in tra o c u la r pressure o r g la u ­ la te d Lh at th e s e p a tie n ts h a v e c a v ila to iy d e fe c ls b e h i n d th e
c o m a . 57" 55 T h e r e is a n in c re a s e d in c id e n c e o f a c q u ire d la m in a c rib ro s a , th e w a lls o f w h ic h co lla p s e w i l h e le v a te d
p its in p a tie n ts w ith to w -le n s io n g la u c o m a [74 % ) versus p re ssu re a n d b e c o m e c o n flu e n t l o lo o b lik e a p i t o r a la ig e
p a tie n ts w ilh ly p ic a l g la u c o m a ( 1 f j l i i ) . "' D e v e lo p m e n t c u p . Is c h e m ic n e c ro sis in eyes w i l h p o o r o p tic n e rv e h e a d
o f t h e p i t m a y b e p r e c e d e d by1 t h e a p p e a r a n c e o n o n e or c ir c u la t io n m a y b e r e s p o n s ib le in s o m e e y e s .''1
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l e a d i n g l o s c h is is -Eik e c h a n g e th a t c a n я р т е й т я p rogress
А : Л Evp ic.il m o rn in g fjlory d e fo r m iLy w ilh a lar^e o p tic cEiне
t o m a c u l a r d e t a c h m e n t . 1'2 " 1' " Ih i s h a s b e e n n o t e d i n a c u t e a n d radial vessels a ris in g near its e d g e . N o t e lh e p e r ip a p il­
a n g le c lo s u re g la u c o m a , ju v e n ile g la u c o m a , tra u m a tic a n d la ry в tro p h y a n d p ig m e n ta tio n .
p rim a ry o p e n -a n g le g l a u c o m a . '['h e a c u t e ris e o r f r e q u e n t В and C : Nil p m i n g g l o r y a n d basal S tjc e p h a Jo c E le
s p ik e s in in tra o c u la r pressure m ay fo rc e flu id in to th e seen o n T l -w e ig h te d n on c o n lra s l sa y iH a ! m a g n e tic reso­
nance i m a g i n g i C . a r r o w , in л п o t h e r w i s e healtEijy l f l - v e a r -
in n e r re tin a t h r o u g h s m a ll d e fe c ts a l th e e d g e o f th e d is c
o ld fe m a le w iIh no liftht p e rc e p tio n vis io n . К o le th e
or cup. The in c re a s in g flu id m a y e v e n t u a l l y d iss e c t i n t o
p e r i p a pi i a r y h y p e r p i [ ^ m e n i a l i o n . H i " o n l y a s s o c i a t i o n w a s a
th e s u b re tin a l sp a c e in s o m e e y e s . L o w e r i n g th e in tr a o c u -
w id e nasal b rid g e .
Ear p r e s s u r e w i t h s u r g e r y o r m e d i c a t i o n s re s u lL s i n r e s o l u ­
D - H : [Jis L c o lo b o m a a ss o c ia te d vi h b a m a c u la r d e la c h n u m l
t i o n o f th e flu id in s o m e eyes; o th e rs re q u ir e a v it r e c to m y in Lh ii 31 -y e a r-o ld fe m a le . Flu o re s c e in a n g io g ja m s h o w s n o
a n d g a s d i s p l a c e m e n t . 1^ t h e s c h is is m a y b e s u b t le a n d h M H i f l u a r e u E l i c e or site o f le a k a g e -iH j. O p L ic a l (in h e re n c e
m a y b e m i s t a k e n f o r c y s t o i d m a c u l a r e d e m a s e c o n d a r y Lo to m o g ra p h y sEiuws s u b re lin a l flu id e m e n d in g From lh e d isc
p ro s ta g la n d in in h ib ito r s o r b e tre a te d w i t h o u t success W ith
ed|^e a n d a separate p o c k e t o f S R F u n d e r I h o fovea I t j , H ) .

to p ic a l n o n s te r o id a l ag en ts. P e rip a p illa ry s ta p h y lo m a .

I a n d |: P e rip a p illa ry s Ea p h y lo m a in the rig h t e y e o f a
С О Ю В О М Л , JU X T A P A P IL L A R Y J l - y e a r - o l d w o m a n c u m p fa in in g o f transient o b s c u ra tio n s
of' vis io n in [his e y e . N o l o d m c irc u la r area erf d e p ig m e n t д-
S T A P H Y L O M A , A N D M O R N IN G lion a n d e x c a v a tio n s u rr o u n d in g lb e o p llc d is c ( J T h e r e w a s
G L O R Y D E F O R M IT Y __________________ slighl n a r r o w in g o f I he relin a l vessels a d ja c e n l lo Ih e o p tic
d isc. V isu a l a c u ity in Lhe li^ h l e ye w iib 2 (V 2 0 a n d in I h e lefl
A c o lo b o m a o f th e o p tic nerve h e a d in v o lv e s a d e fe c t In e ye w a n 2 0 / 1 .'i. TEie lefl fu n d u s w a s n o rm a l : | ).
K : M a r k e d p e r ip a p illa r y s ta p h y lo m a , [he w a its о I w h ic h c o n ­
Els s t r u c t u r e o c c u r r i n g a s a r e s u l t o f m a J c l o s u r e o f t h e o c u -
tracted a b o u t e v e r y m in u te lo fa rm a CaVSty a p p r o x im a te ly
E a r f i s s u r e . It m a y h e m i l d , , i n w h i c h c a s e t h e r e i s a d e f e c t
tw o -th ird s o f the d ia m e le r s h o w n .
in th e o p tic n e rv e su b sta n c e , u s u a lly in fe rio riy . Ih is d e fe c t L a n d M : P h o to m ic ro g ra p h s ot" a cro s s -s e c tio n o f the d ys -
m a y h e m o r e ел t e n s i v e a n t i i n v o l v e t h e j u x t a p a p i E l a r y c h o ­ plastic o p tic n e rv e ju s t b e h in d th e e y e o f a p a tie n t w ith a
r o id a n d re tin a . It m a y b e a s s o c ia te d w i t h a p it d e f o r m i t y p e rip a p illa ry s ta p h y lo m a . N o l e lh e d ys p la s lic n e rv e sur­
and w ith a ju A ta p a p illa ry s ta p h ylo m a . T h is la tte r te rm ro u n d e d b y a rin g o f s m o o th m u s c le (a rra w s k C o n tra c tio n
re fe rs to an o u Lp o u c b in g o f th e o c u la r w a ll aroun d th e oE s im ila r a tavistic m u s c le is a p p a re n tly re s p o n sib le for the
s p o n fa rte o Js conLra cLron n o te d in the p a lie n t 'К ) .
o p tic n e rv e h e a d . !h is o u tp o u c h in g m a y o c c u r w iLh little
or no a b n o rm a lity in th e stru c tu re a n d fu n c tio n o f th e |Q jnrj F-:A k u r VL:nnuj;^i L J .. IIil1 k!-.-l n i-il A L lj!. SjurtiJer] 2C1I0,
7(IJ0 -iJ2 (J-5 . p.
e y e , o r W ith v a r y in g d e g re e o f d y s p la s ia o f th e n e rv e , [ f th e
c o l o b o m a o r s t a p h y l o m a is f i l l e d w i t h g l i a l t i s s u e , t h e r e t i ­
n a l b l o o d ve sse ls m a y e x it f r o m t h is tis s u e in a p a tt e r n t h a t and LJ. ih e s e d e ta c h m e n ts, tike th o s e a s s o c ia te d w i t h a
h its s u g g e s t e d to som e a m o rn in g g lo ry [E:ig u re 1 5 .0 2 K p it, m ay re s o lve s p o n ta n e o u s ly /"' 'ih e p a ltto g e n e s is of
and L). t h ese m o r e severe a n o m a lie s o f th e o p tic d is c m a y th e d e ta c h m e n t o c c u rrin g w ith a ll o f th e s e a n o m a lie s is
be a s s o c ia te d w ith serou s m a c u la r d e ta c h m e n t (fig u re p ro b a b ly s im ila r in m ost casesr a lth o u g h th is is c o n t r o ­
1 5 .0 4 D - H ) ; w ith o th e r o c u la r a b n o rm a litie s , in c lu d ­ ve rs ia l. In th e m o rn in g g lo ry d e fo rm ity and iu x ta p a p il-
in g m ic ro p h th a lm o s , le n s c o lo b o m a , p e rs is te n t p rim a ry ia ry s la p h y lo m a . Lhe d e ta c h m e n t has been a ttrib u te d
h y p e r p l a s t i c v i t r e o u s , o r b i t a l c y s t ^ 115" ™ and o c c a s io n a lly t o re tin a l b r e a k s in th e v ic in ity o f th e a n o m a l y , 141 4 lo
in tra c ra n ia l a b n o rm a litie s such as a b a sa l e n c e p h a lo c e le c o m m u n ic a tio n b e tw e e n th e s u b a ra c h n o id and s u b re ti­
[ F i g u r e 35 . 0 4 В a n d C ) , a n d m i d l i n e d e f e c t s i n c l u d i n g p i t u ­ nal s p a c e .1 lo c o m m u n ic a tio n b e tw e e n th e v itre o u s
i t a r y s t a l k d u p l i c a t i o n , a n d m o y a m o y a d i s e a s e . - : !“ : and s u b r e tin a l s p a c e ,s ' to c o m m u n i c a t i o n w ith b o th th e
A p i t d e f o r m i t y m a y o r i n a y n o t b e p r e s e n t a n d is o f t e n vitre o u s and s u b a ra c h n o id s p a c e / " 1, t o vitre o re tin a l tra c­
o b s c u r e d c lin ic a lly b y o t h e r a n o m a l i e s [E 'ig u r e ] 5 . 0 2 K a n d tio n / '^ and lo e x u d a tio n fro m b lo o d ve sse ls w ith in th e
LJ. En s o m e cases th es e a n o m a lie s m ay be c o m b in e d to a n o m a l y / ’’ 1' t h e o r b i t a l t i s s u e , 'JU a n d ju x ta p a p illa ry c h o r io -
fo rm a m a s s le s io n s im u la tin g a c a p illa ry a n g io m a , astro - c a p i l l a r i s . ''" V i t r e o r e t i n a E t r a c t i o n is p r o b a b l y i m p o r t a n t i n
t y to m a r c o m b in e d re tin a l-R ^ E, h a m a rto m a , o r m e la n o m a a ll c a s e s , a n d s u c c e s s f u l r e p a i r o f t h e d e t a c h m e n t h a s b e e n
fFig u re I 5 .0 4 B ) in th e re g io n o f th e o p tic d i s c . 1* 3 S o m e a c c o m p lis h e d by v itre c to m y , in tra v itre a l gas, and th e r­
p a tie n ts m a y m a n if e s t c lin ic a l e v id e n c e o f c o m m u n i c a t i o n m a l t r e a t m e n t a t t h e e d g e o f t h e a n o m a l y / ' ' ^" C h o r o i d a l
b e tw e e n th e v itre o u s a n d r e t r o b u lb a r o c u la r cysts v ia th e n e o v a s c u la r iz a tio n m a y o c c u r a l th e e d g e o f a n y o f th es e
o p t i c d is c a n o r p ( ilfe s ,tf:f llf iJ In p a tie n ts w i t h th e s e severe a n o m a l i e s > , ^ ^ i -, h '
d is c a n o m a lie s th e re tin a l d e t a c h m e n t b e g in s i n t h e jujc- h a m ilia ! cases h a v e b e e n a s s o c ia te d w i l h m u ta tio n s in
ta p a p itla ry area, o fle n o n t h e t e m p o r a l s i d e . ^ - ' " 11 th e P A X 6 g e n e on ch ro m o som e l ] p ] 3 ' jv; E t o w e v e r , g i v e n
lh e d e ta c h m e n t, u n lik e th at o c c u rrin g w ith a p i t nil o n e , th e a s s o c ia tio n o f tn o rn in g g lo Ty d is c s w ith d is s im ila r
m a y e x t e n d t o i n v o l v e m o s t o f th e f u n d u s [E: ig u r e E 5 .0 2 K a n o m a l i e s , a m o r e c o m p l e x g e n e t i c i n f l u e n c e is L i k e l y .
 15-.0 -i P e r ip a p t ll a r y s l a p h y E o т а { С o n ti n u e d )
T R A N S IE N T O B S C U R A T IO N
O F V IS IO N S E C O N D A R Y T O N : .Me?re Fully developed peripapillary staphyloma in a
17-year-old ^irl w ilh a Э-year history of intermittent episodes
P E R IP A P IL L A R Y S T A P H Y L O M A □f com plele anrmurosiH in lhe loll eye.

P e rip a p illa ry s ta p h y lo m a is a r a r e c o n g e n i t a l a n o m a l y in P a p f llo r e n a l s y n d r o m e Ir e n a l c o l o b o m a s y n d r o m e }

w h i c h t h e n o r m a l o r n e a r l y n o r m a l o p t i c n e r v e h e a d lies i n О a rid F*: Th i-s .Ы -уиаг-Ы с1 g r a d u a l*1 sLudent g a v e a histoTy
th e d e p t h o f a n e x c a v a tio n in th e fu n d u s [F ig u r e 1 5 . 0 4 lr K , ul u n d e rg o in g laser tre a tm e n t Lo h£s right o p tic n e rv e a I age
3 . H is visuaE a c u ity w a s 2 0 / 2 0 O U . H e c o m p la in e d o f righl
a n d N ) . !t is u s u a l l y p r e s e n t i n o n l y o n e e y e . il" t h e s t a p h y ­
fla n k p a in a n d w as k n o w n lo have sm all k id n e ys for lh e p re ­
l o m a d o e s n o t in v o lv e th e m a c u la , th e v is u a l a c u ily m a y b e
v io u s ti ye a rs : this w as disctifcSred w h e n h e w a s scre e n e d as
n o r m a l ( I ' i g u r e 1 .5 .0 4 1 a n d N ) . I n a d u l t h o o d t h e s e p a t i e n t s fi p o te n tia l k jd n e y d o n o r for his m o th e r, w h o h a d e n d -s ta g e
m a y c o m p la in o f tra n s ie n t o b s c u r a t io n s o f v is io n t h a t in renal disease for 1 3 y e a rs . H i s c re a tin in e c le a ra n c e w a s
д о щ е cases m ay b e a s s o c ia te d w ith in te rm itte n t d ila tio n d e c re a se d a n d hEs b lo o d p re ssu re w a s e le v a te d . A sister a n d
o f l h e r e l i n a l v e i n s . ' ' 4 ' lQI Rgu re i.S .0 4 1 illu s tra te s a m i l d n ie c e w e re k n o w n to h a ve a b n o r m a l renal f u n d io n a n d renal
d e g re e o f p e ri p a p illa ry s t a p h y io m a l o u s f o r m a t i o n t h a t w a s
s lo n e s . H ie vessels c o m e o il the d is c at its e d g e a n d the c e n ­
tral area o f Ih e d is c js "v a c a n t^ ' ( O . P I. La s e r scar is веер in
in itia lly m is in te rp re te d as a c h o r o id a l h e m a n g io m a in a
Ihe te m p o ra l ju x la p a p illa r y ret т а . H o r iz o n t a l sliia e le m p o -
y o u n g i v o m a n W i t h t r a n s i e n t o b s c u r a t i o n s o f v i s i o n . '■1
ru lo i h f I i к cl v нi;^n i I v p rtv io u -- SKI-. A ■ li n k .i l •: 1 .1gnosis
P e r ip a p illa r y s t a p h y l o m a t a m a y o c c a s io n a lly b e a s s o c ia te d o f p a p illo re n a l s y n d ro m e w a s m a d e a n d th e p a lie n l a n d the
w i t h c o n tra c tile m o v e m e n t s o f t h e w a lls o f t h e s t a p h y lo m a fa m ily are b e in g fu rth e r in ve s tig a te d to c o n firm the d ia g n o s is .
(Lig u re E 5 . i ) 4 K ) . ILI" 1111 I h e s e c o n t r a c t i o n s a r e n o t a s s o c i a t e d Q - 5 lh is 3 7 -y e a r -o ld m a le h a d und ergon e* a c a d a v e ric renal
w i t h t h e p a t i e n t ' s r e s p i r a t i o n o r p u l s e r a t e . I h e r e is s o m e h i s ­ tra nsplant fo r "o n d -s la g e ren al disease^ w ith h y p e rte n s io n
t o p a t h o lo g ic e v id e n c e l o s u g g e st th a t tb e p re s e n c e o f a ta vis tic at age 2 b . H e pre senLed w i lh a n o n rh e g m a to g e n o u s retinal
d e La c h m u n l in lh e rii^hl e y e a n d ch a n g e s al the p ig m e n t e p i­
s m o o th m u s c le in and around p e rip a p illa ry s ta p h y lo m a ta
th e liu m in Fjolh m a c u la I Q anrl K j; lhis w a s Ih o u g h l lo b e
m a y b e r e s p o n s i b l e f o r t h is c o n t r a c t i o n a n d ., fu r t h e r , m a y b e
related to c h ro n ic I C i L / o r ^ a n tra n s p la n l re tin o p a th y s u p e r­
re sp o n sib le fo r th e tra n s ie n t o b s c u r a tio n o f v is io n [Lig u re im p o s e d o n a n " a n o m a lo u s d is c ." K r y p t o n laser to Ihe te m ­
1 5 .0 4 1 . a n d М } . л: C o n tra c tile m o v e m e n ts have a ls o been poral e d g e p f Ihe rig h t o p lic d is c failed to re s o lve lh e relinal
d e s c r ib e d in p a Lie n ts w i l h c h o r o i d a l c o l o b o m a a n d m o r n i n g d e ln c h m e n f re q u irin g a pare p la n a v itre c to m y a n d e n d o
g lo ry s y n d r o m e " 1 in 1У62 Lo n g fe llo w and cow orkers d ra in a g e ( Q i a rro w at d ra in a g e si lei. C a rural e x a m in a tio n
re p o rte d a young m an w ilh u n ila te ra l in te rm itte n t b lin d ­
sEujws b o lh o p lic discs t o b e " v a c a n l" c e n tra I ly w ilh vessels
arisin g at the e d g e , s o m e o f w h ic h a re " h a ir p in -lik e ," ty p ic a l
ness a s s o c ia te d w i t h m a r k e d d i l a t i o n o f t h e re lin a l v e in s o f
o f jia p ilio re n a l s y n d ro m e {tjJ-S J.
u n d e t e r m i n e d c a u s e 1'"" H e h a d m i n i m a l a b n o r m a l i t y o f t h e
T - V : T h e rig h l e y e in Lhis 5 -m o n th -u -ld N ig e r ia n A m c r L c a n gLrl
o p lic n e r v e h e a d , b u t lh e c lin ic a l f i n d i n g o th e r w is e su g g e st w ilh p e n d u la r nys ta g m u s a n d h y p o p la s tic S id n e y s , reveals
th e p o s s ib ility o f an a n o m a lo u s s m o o th -m u s c le s p h in c te r sei^nenlaF a n d :s im u lla n o o u s fillin g o f lh e su p e rio r c h o ro id ,
a r o u n d th e re tr o b u lb a r o p tic nerve. retina a n d disc vessels d u rin g the e a rly arterial p h a s e ( U ) .
R e la tiv e n o n -p e rfu s io n o f i Fh j inferior t ■lonoiilal a n d retinal
vascu la tu re is seen lh at fills in a la let a n g io g ra m (V k T h e re is
a W ale.Kihed are a o l retinal a n d c h o ro id a l non-|>crfusior> fro m
P A P IL L O R E N A L (REN A L the disc that e xte n d s in fe ro te m p o ra lly (a rro w s , V ) . N o d istinct
C O LO BO M A ) SYN D RO M E foveal avascular z o n e w as present. This paLaenl also la cked
b o lh reLtnaE a n d c Fw ro id a l p e rfu s io n in the inferonasal p e r ip h ­
h irst d e s c r i b e d in 1 9 7 7 b y R ie g e r f lft' i t w a s c o n s i d e r e d l o b e a ery w h e re Lhe retinal vessels e n d -a n a s to m o s e d at trie e d g e o f
retinal p e rfu s io n . T h e lefl d is c h a d n o central retinal vessels
ra re a u t o s o m a l d o m i n a n t d is o r d e r o f t h e o p L ic d isc a n d k i d ­
Ino! s h o w n I. Н и N ig e r ia n fa th e r w iLh 2 0 / 2 0 a-ruily b ila leralJy
neys. W o r k b y P a is a a n d c o lle a g u e s su g ge sts th a t th e h i g h l y
h a d o p tic discs w ith h a irp in vessels arisin g a I Ihe d is c e d g e .
V a r i a b l e : p h e n o t y p e m a y b e r e s p o n s i b l e f o r its u n d e i d i a g n o -
W - Y : Th is 4 9 -y e a r-o ld A fr ic a n A m e r ic a n w o m a n s u ffe re d
sls. I n itia l d e s c r i p t i o n w a s o f a n o m a l o u s o p t i c d is c s a s s o c i­ re c u rre n t p y le o n e p h r itis . B o lh o p tic discs h a d vessels arising
a te d w i l h h y p o p la s t ic k id n e y s re s u ltin g in h y p e r te n s io n a n d aL Ihe I’ d g e o l the disc w ilh ru d im e n la r y c e n lra l d is c vessels
renal fa ilu re . Serous re lin a ! d e ta c h m e n t e x te n d in g lo th e tW a n d V . M id p h a s e a n g io g ra m on Lbe disc reveals v e ry
m a c u l a a c c o m p a n i e s t h e d i s c a n o m a l i e s i n s o m e c a s e s . ' 14 1111 sm all c e n tra l retinal vessels.
'ih e e xte n d e d o p h th a lm ic fe a tu re s o f p a p illo re n a l syn­ ltd a n d C , L i o u r t L - s y ( j f L J r . M . I .L r i q j L+ h . l I[ i L J - l i , -: :i m j r l i . ' . и Г i > i . t d w и
M . +’ v , i r i Ir, О . i i i d к in V .ii -i n u z j c i , L i w r t f i t f c A . I h « hl ciL in .il A l T l n .
d rom e in c lu d e !a ig e o p Lie d i s c s w ith several c ilio re tin a l
P tliLc b jT u h ta Ж 1К1. p .ВЭ5 ] ni rit! ? ( г и г и S c , !> i ; Ji l r u i d
arteries w i t h h a i r p i n - 1i k e l o o p s e m e r g i n g a t t h e e d g e o f t h e K , ( . i j u rlcijsy u f O r . A H . l - r t ' d v r i c k f r ; L . iг i■:J L t i u r l e h v o l I )r .

d isc ( L i g u r e IE L0 4 0 -S ). A la rg e p o r t i o n o f t h e c e n tra l parL W illia m I I . S | j t i i i L r. ( > . , n i j И r : i i L i r l L " , y Ml U r . L n u i r i ' M . l w ii;

Г к н У . L O L i r t L i v <j1 D 17 С » m ttr m I 3, i r ; . г ..11лг i м гE vviLh р т г и м п ш Iron»

o f t h e d isc is d e v o i d o f ve sse ls o r h a s r u d im e n ta r y c ilio -
U f > h l h . i I r n L i Н з ц у . h l M . ' v i t T 1 " 5' . -
re lin a l ve sse ls. A l o n g w i l h m u l l i p l e c ilio r e t in a l v e sse ls, t h e
r e t i n a l v a s c u l a t u r e is n o t f u l l y d e v e l o p e d , a n d th e c h o ro id le an u rs h a v e a p o o r l y d e f i n e d c e n tra l r e tin a l a rte ry a n d v e in
es a f f e c t e d lo v a rio u s degrees in c e rta in fa m ilie s (I'ig u r e and m o s t o f Lhe re tin a l c irc u la tio n is d e r i v e d f r o m c ilia ry
1 5 . 0 4 ' E - V ) . It a p p e a r s t h a t t h e r e m a y h e a p r i m a r y d e f i c i e n c y ve sse ls tn ih e s e a n im a ts , lh e eyes w ith p a p illo re n a l s y n ­
En t h e v a s c u l a r d e v e l o p m e n t th a t c o m p r o m is e s g ro w th of d r o m e s e e m t o h a s 'e c o n v e r t e d l o t h i s f e l i n e p a t t e r n o f c i r c u ­
s u b s ta n tia l p o r t io n o f th e re tin a a n d th e c h o r o id . C a ts a n d la tio n L a p i l l o r e n a l s y n d r o m e is l i k e l y a h e r e d i t a r y v a s c u l a r
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d y s g e n e s is th is t m o s L s e v e r e l y a f f e c t s t h e o c u la r a n d renal t5-.il"; H y p o p l a s i a a n d d y s p la s ia o f i h e o p t i c d is c .
c irc u la tio n , th e m o s t v a s c u la r o rg a n s . V is u a l fie ld d e fe c ts
Д : .M a rk e d h y p o p la s ia o f [he o p tic d is c in ал in la n l.
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t h i s is e x p l a i n e d b y l h e a b s e n c e o f r e t i n a l g a n g l i o n c e l l s a n d С rind D : U n ila te ra l o p lic disc h y p o p la s ia in It?ft e y e iD l o f a
decreased re lin a l th ic k n e s s as a re su lt o f d e fe c t in th e vas- y o u n g w o m a n w h o h a d n o rm a l v is u a l a c u ily in b o th eyes b u l
c u lo g e n e s is o f th e re tin a a n d c h o r o id . M a g n e tic re so n a n c e □л a fferu n l p u p illa ry defeat a n d a p e c u lia r vis-ил I fr d d d e fe at
im a g in g ( M W ) s h o w s h y p o p la s ia o f th e o p tic c h ia s m due
in lh e left e y e . C o m p a r e w f lh n o rm a l l ijiiil d is c I L I .

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h a d s U a e -K r t*n p a fa l v is u a l lie ld defeclh in b o th e y e s :
s ig n ific a n t n u m b e r o f th e s e discs m a y b e m i s d ia g n o s e d as
F a n d C : ie p t o -u p lic d ysp lasia In a 17-y e a r-o ld girl w h o w a s
m o r n i n g g l o r y o r n o r m a l - t e n s i o n g l a u c o m a , 'l h e a s s o c ia te d
the p r o d u c t o f fu ll-te rm n o rm a l p re g n a n c y a n d d e liv e ry , S h e
k i d n e y d ise a se s in c lu d e renal h y p o p la s ia , ren al h y p e rte n ­ h a d tieCm alal ja u n d ic e c a u s e d b y H it in c o m p a lib M ily . S h e
s i o n . a n d r e n a l f a i l u r e , I h e r e is e x t r e m e r e s i s t a n c e t o r e n a l was- o f short Statunjjt i h e h a d nysta gjm is .in d c o n c e n liic field
b lo o d How w i t h in th e re n a l p a r e n c h y m a re s u ltin g in re n a l c o n s tric tio n . H e r vis u a l a c u ity righl e y e , w a s 2Q/-60 a n d , led
h y p e rte n s io n . The re current p y e lo n e p h ritis and k id n e y
e y e , no lig h t p e r c e p tio n . M a g n e tic re s o n a n c e im a g in g ( M K ^
s h o w e d e v id e n c e ol aplasia o f the s tip lu m |>ellL±cidum.
s t o n e s is a v a r i a n t o f e x p r e s s i o n o f t h e r e n a l d i s e a s e .
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'ih e r e m ay be several d e fe c ts in th e ГАХ2 gene Lo
lu c id u m seen o n c o ro n a l Mb? I in ihin E ti-y e a r-o ld pa Lien I.
a c c o u n t fo r th e v a ria b le p h e n o ty p e . In I У 9 5 , S a n y a n u s in
ririrE U. LiJurtL^y inf Ur. [oH i GUiMijf hi—Jr iflifcrtEiy erf Ur. KitriLk
et a l. d is c o v e re d m u ta tio n s in th e d e v e lo p m e n ta l gene Livin.J
PAX2 in tw o fa m ilie s w ith p a p illo re n a l s y n d r o m e . Ji;3,113
S c h i m m e n t i e t a l. i d e n t i f i e d th re e a d d i t i o n a l f a m ilie s w i t h
o c u la r and renal a b n o rm a litie s , in c lu d in g v e s ic o u re te ra l H e d ir e c t ly m e a s u r e d th e h o r i z o n t a l d i a m e t e r o f th e d iscs

r e f l u x .4 ' S in c e t h e n five o t h e r f a m ilie s w i t h m u ta tio n s o f la k e n o n a s t a n d a r d 3 0 d e g r e e fie ld f u n d u s c a m e r a i v i t h a

th e P A X 2 g e n e h a w b e e n r e p o r t e d . 11' ' " 1, H o w e v e r , n o t a ll x l.5 m a g n ific a tio n . I h e range in d ia m e te r s fo r h y p o p la s tic

cases c a n b e e x p la in e d b y th e Г Л Х 2 m u ta tio n s . discs w a s I .й - 3 .2 7 m m , w ith a m e a n o f 2 .6 4 m m , as c o m ­

lh e fe a tu re s th at s h o u ld a ie rl a d ia g n o s is o f p a p illo - p a r e d to a ra n g e o f 3 4 4 - 4 . 7 m m and a m e a n o f Э .Д 8 m m

renat syndrom e in c lu d e th e "vacant d is c s / presence o f f o r n o r m a l d iscs . Z e k i a n d o t h e r s u s e d t h e r a t io o f th e d i s ­

m u l t i p l e c ilia r y r e tin a l ve sse ls w i t h th e ir a b n o r m a l in se r­ tan c e fr o m t h e e d g e o f th e d is c t o th e c e n Le r o f th e fo v e a

tio n p o s te rio r lo th e g lo b e , p e rip h e ra l d y s g e n e s is o f th e lo d is c d i a m e t e r Lo d e fin e o p t i c d isc h y p o p l a s i a ; a r a tio o f

r e t in a ] ve sse ls- h y p o p l a s i a o f th e o p t i c c h i a s m o n K i R I , a n d 3 to 1 o r g re a te r c h a r a c te r iz e s a h y p o p l a s t i c o p l i c d i s c .|JS

v i s u a l f i e l d d e f e c t s l h a t d o n o t c o r r e s p o n d t o g l a u c o m a . ' 1 "' D is c h y p o p la s ia m ay be u n ila te ra l or b ila te ra l (['ig u r e

IB .0 5 С a n d !> ). In b ila te ra l cases th e eye w i t h Lhe s m a lle r
d isc o f t e n has a b e tte r S n e lle n a c u ity, in d ic a t in g th a t fa c ­
OPTIC DISC HYPOPLASIA AND to rs o t h e r th a n s ize d e te rm in e th e v is u a l fu n c tio n , e .g .,

T1LTED-DISC SY N DR O M E m a c u l a r h y p o p la s ia , h ig h re fra c tive e rro r, a m b l y o p i a , c e n ­

t r a l s c o t o m a , a n d o p t i c a t r o p h y . 12(1 A h y p o p l a s t i c d i s c w i t h

M ild d y s p la s ia o f th e o p tic n e rve m u s t b e c o n s id e re d in a la rg e c e n tra l c u p m ay h a v e a d is c d ia m e t e r o f n o r m a l

p a tie n ts w i t h u n e xp la in e d v i s u a l l o s s . " 1-1 ■' ' [ ' h e r e i s c o n ­ s i z e . 1 -'1 E l y p o p l a s t i c o p l i c d i s c s m a y o c c a s io n a lly be s u p ­

s id e ra b le v a ria tio n in lh e s ize o f th e norm al o p tic d isc . p lie d Ea rg e ly b y c ili o r e l i n a l a rte rie s . ' - s D i s c h y p o p l a s i a m a y

Ih e d i s c d i a m e t e r is o f t e n d i r e c t l y r e l a t e d t o e y e s i z e a n d he a s s o c ia te d w it h o th e r e x lr a o c u la r o r in tr a o c u la r a n o m a ­

re fra c tive e rro r. S o m e a n o m a l i e s o f th e d is c m a y h e e ith e r l i e s { e . g . , a n i r i d i a } 1 -'"; i t m a y b e s e g m e n t a l ' ■ and it m a y

o v e rlo o k e d or m is in te rp re te d as p a p ille d e m a . H a ilu re Lo he a s s o c ia te d w ilh norm al v is u a l a c u ily (fig u re 1 5 .0 Б С

re c o g n iz e a d is c a n o m a l y i n a p a tie n t w i t h a v is u a l d e fe c t and t ) J . |in S u p e r i o r s e g m e n t a l d is c h y p o p l a s i a m ay occur

m a y cause in itia tio n o f a n u n n e c e s s a rily e xte n s ive e v a lu a ­ a s a s i g n o f m a t e r n a l d i a b e t e s 1 ■lL ш a n d can b e d ia g n o s e d

tio n fo r a re tin a l, re tr o b u lb a r , o r in tra c ra n ia l le s io n . b y f i n d i n g c h a r a c t e r i s t i c i n f e r i o r v i s u a l f i e l d , d e f e c t s . 1 ■'

M o d e ra te or severe h y p o p la s ia o f th e o p tic d isc is O p lic n erve ln yp o p la sia ca n re su lt f r o m a n in s u lL to th e

o fte n a s s o c ia te d w i l h a v is u a l d e fe c t [Ijg u re 1 5 . U 5 J . — !- 1 em bryo a t a n y le ve l o f th e o p lic p a th w a y .1 b v id e n c e fo r

O p h t h a l m o s c o p i c c l u e s Lo its p r e s e n c e in c lu d e re d u c tio n a n e u ro e n d o c rin e d is o rd e r s h o u ld b e s o u g h t in a n y c h ild

in th e d isc d ia m e te r , a l o w d is c /a rte ry ra tio , a n d t h e p e r i­ p re s e n tin g w iL h b ila te ra l o p t i c d isc h y p o p la s ia , because o f

p a p illa r y d o u b l e - r in g s ig n ( F ig u r e 1 5 .0 5 Л a n d B ) . T h is s ig n th e fre q u e n t a s s o c ia tio n o f h y p o th a la m ic a n d p itu ita ry d y s ­

c o n s is ts o f a y e llo w -g r a y p e r ip a p illa r y h a lo d e lin e a te d b y f u n c t i o n , p a rtia l o r c o m p le t e a b s e n c e o f t h e s e p t u m p e llu -

an o u te r rin g c o r r e s p o n d in g lo th e ju n c tio n b e tw e e n th e c id u m , m id b r a in a b n o rm a litie s , b y p o L o n ia , h y d ro c e p h a lu s ,

s c le ra and la m in a c rib ro s a and an in n e r rin g caused by p o re n c e p h a ly , a n d o rth o p e d ic d e fo rm itie s (d e M o r s ie r s s y n ­

th e te rm in a tio n o f th e R I J t . ' - j Li4, d ia g n o s is o f m ild d r o m e ) ( E -'i g u r e 1 5 . Q B D and O th e r k n o w n asso­

degrees o f h y p o p la s ia m ay be d iffic u lt or im p o s s ib le . c ia tio n s in c lu d e a n irid ia , m o n o c u la r te m p o ra l h e m ia n o p s ia ,

Several te c h n iq u e s f o r m e a s u r i n g a rid d e fin in g o p tic d is c co n tra la te ra l m e g a lo p a p illa , m ic ro p h th a lm ia , a c h ia s m ia .

h y p o p la s ia have been d e s c r i b e d . K o ma n o . u s in g p o ly m ic ro g y ria , p e rio d ic a lte rn a tin g -g a a e n ys ta g m u s , in tra ­

p h o L o g r a m e tric m e th o d s, fo u n d no o v e rla p b e tw e e n th e c ra n ia l a r a c h n o i d c y s t, o v a l c o r n e a a n d le n s d u p l i c a t i o n , t o r ­

h o rizo n ta l d ia m e te rs o f n o r m a l a n d h y p o p la s tic d i s c s . ' t u o u s re tin a l v e in s , a n d m i t o c h o n d r i a l c y t o p a i h i e s .1 : 1' : ' '

 1q а 10 0 -c a s e s e r ie s o p t i c n e r v e h y p o p l a s i a W a s a sso c i- \ 5 .0 6 H y a lin e b o d ie s o l (h e o p t ic d is c .

лL&J w ith p re m a tu r e b irth [ 2 1 % ) , m a te rn a l d ia b e te s { 6 % ) ,

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ties [ 6 % ) . T h i r t y - t w o p e r c e n t h a d a s s o c ia te d d e v e l o p m e n t a l as p a p ille d e m a . N o l e lh e c o n g e n ita l lort urss i ly o f Lhe relinal
d e la y , 13% c e r e b r a l p a b y , a c id 1 1 % s e i z u r e s . S i x t y p e r c e [tL vessels a n d lh e re la tiv e ly s m a ll, less in v o lv e d lefL o p tic d isc.
had ab norm al n e u r o i m a g in g , in c lu d in g v e n tric u la r and iu b ie lin a l h e m o rrh a g e la rro w } c ^ e d b y c a lc ifie d h y a ­
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line bctdies.
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a n te rio rly lo the la m in a crib co sa . N o t e m u ltip le d ila te d c a p il­
c e p h a l u s . A s s o c i a t e d c l i n i c a l n e u r o l o g i c a l d e fic its w e re s e e n
la rity : a rro w s ■n e a r Lbe m a rg in s o f lh e h y a lin e b o d y .
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tric i n v e r s io n o f c h r o m o s o m e 9, tris o m y l f l r !>p d e l e l i o n I I m m H f j resume Lively. Ltolh o p tic discs w e r e .u m p y - b u m p v
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th e lo n g a x i s o f t h e o v a l o p t i c d i s c is o b l i q u e l y d i r e c t e d ; tion fillers i t i , Ю s h o w e d in c re a se d .n jlo flu o re s c e n c L1 in Liolh
th e u p p e r a n d t e m p o r a l p o r l i o r o f t h e d is c lie s a n t e r i o r e ye s. O p iic a l c o h e re n c e Lorfiog^aphy s h o w e d raised n o d u la r
to Lhe i n f e r o n a s a l p o r t i o n ; th e r e t in a l ve sse ls e m e r g e f r o m surface w ilh in cre a se d re fle c ta n c e ol b o lb discs i H , L :.
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f i e l d d e p r e s s i o n o c c u r s b i t e m p o r a l Ey ( n o t t r u l y h e r n i a n o - o f v is u a l fie ld s (c h a ra c te ris tic a lly in fe m n a s a t) in a nerve
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fib e r d i s t r i b u t i o n .1' 1 Drusen m ay be a sso c ia te d w ith
be a ffe c te d . T h e a s y m m e t r y o f th e d is c e le v a tio n w i t h th e a b n o r m a l v is u a l e v o k e d p o te n tia ls .^ 178 I n a fe w p a tie n ts
ill-d e fin e d m a rg in s s u p e rio rly m ay be m is ta k e n fo r p a p ­
d ru s e n o f th e o p tic d is c m a y le a d to s e v e re lo ss o f c e n tr a l
i l le d e m a . V is u a l lo ss m a y b e c a u s e d o c c a s io n a lly b y c h o ­ y i a J t m .lM ,i r e D r u s e n m a y a ls o c a u s e a c u te v is u a l Joss, p r e ­
r o i d a l n e o v a s c u l a r i z a t i o n . 1 ''' l " h e d i s c a n o m a l y m ay occur
s u m a b ly re s u ltin g f r o m acute s w e llin g o f th e o p tic nerve
i n a s s o c i a t i o n w i t h , o t h e r , n o n o c u l a r a n o m a l i e s . 139 h e a d in d u c e d b y th e d ru s e n in te rfe rin g w ith th e b l o o d s u p ­
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n e rv e re p o rte d in 2 % o f p o p u la tio n .1 In s m a ll n u m b e r s o f th e c e n tr a l r e t i n a l v e s s e ls .1’ 4 t yes
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n e rv e h e a d . In la rg e r n u m b e r s In c h ild r e n a n d y o u n g a d u lts , to rs, p a tt e r n o f v is u a l fie ld to ssr a n d In c id e n c e o f s e c o n d e ye
th e y cause a s w o lle n nerve b e a d th at m a y s im u la te p a p ill­ i n v o l v e m e n t a re s im ila r t o e y e s w i t h o u t d isc d r u s e n : how­
e d e m a (Fig u re 1 5 .06A a n d В ) .1 A s L h e y b e c o m e L a r g e r, m o r e e v e r t h e y a re y o u n g e r , e n j o y a h e lle r p ro g n o s is , a n d m ore
c a lc ifie d , a n d a sso c ia te d w i t h a t r o p h y o f s u r r o u n d i n g n e rve o f t e n r e p o r t t r a n s i e n t v i s u a l o b s c u r a t i o n s . 1 ,0 O p t i c d i s c d r n -
fib e rs , th e y becom e visib le as d i s c r e t e c r y s t a l l i n e s t r u c t u r e s s e n m a y a ls o c a u s e lo ss o f v i s i o n a s s o c ia te d w i t h s u b r e tin a l
E a t e r i n Life [ F i g u r e 1 5 .0 6 C a n d E a n d L 5 .0 7 ] a n d K ) . W h e n e x u d a tio n a n d h e m o r r h a g e d e rive d fr o m p e r ip a p illa r y c h o ­
b u r i e d , t h e y are m o s t e a s ily d e t e c te d tjy r e t r o i l h i m i a i a l i o n b i o - r o i d a l n e o v a s c u l a r i z a t i o n ( F i g u r e L 5 . 0 7 A - F ] . ' ' " ' |O|: H l e e d i n g
m ic ro s c o p ic a lly . A l t h o u g h a " L u m p y , b u m p y '" a p p e a ra n c e to a in lo th e s u b re tln a l space rm iy o c c u r a d ja c e n t t o t h e o p Lie
s w o lle n d is c su gge sts th e p re s e n c e o f d r u s e n ( F i g u r e 1 5 . 0 6 F - d isc in th e a b s e n c e o f a n g i o g r a p h ic e v id e n c e o f s u b re tin a l
l_), a s i m i l a r p i c t u r e o c c a s i o n a l t y o c c u r s i n р а р И к ч к ’ т л . 160 n e o v a s c u la riza tio n (Fig u re 1 5 . 0 7 Л ) . 1'1' V e r y ra re ly P u lfr ic h
l h e y f r e q u e n t l y o c c u r in s m a l l d iscs a n d m a y b e a s s o c ia te d p h e n o m e n o n is r e p o r t e d , l i k e l y f r o m d e l a y e d c o n d u c t i o n i n
w ith a n o m a l o u s b r a n c h in g a n d to rtu o s ity o f th e re tin a l ves- o n e e y e c o m p a r e d t o th e o t h e r , a n d th is c a n b e m i n i m i z e d
se Is ( f i g u r e s 1 5 . 0 6 A a n d Й a n d 1 5 . 0 7 A a n d b ) . 1 "1 1 " ' In ' u s i n g a t i n t e d Lens o n t h e a f f e c t e d s id e .
 O th e r fu n d u s fin d in g s th at Ш occurred in a sso c ia ­ \5 .0 7 H y a lin e b o d ie s o f th e o p l i c d is c .

tio n w ith d ru s e n o f th e o p tic n e rv e h e a d in c lu d e re tin itis

A - F : Serous and h e m o n h a jjic disciform d etachm ent o f [h e lefl
p i g m e n t o s a , 3 r J - 196 r e t i n a l h e m o r r h a g e s , lbVl a n g i o i d s t r e a k s m acuEa i Й) se c o n d a ry to h ya lin e b o d ie s o f (he optic; d is c in a
i n p a t i e n t s W i t h p s e u d o x a n l h e n n a e l a s L i e u m 1''"' ( s e e f i g u r e 4 -ye a r-o ld b o y w ilh л 3 -w e e k history ol lefl esotropia. Visual
З .З Й 1 a n d 3 . 4 0 H l o L .J s u b f o v e a ! c h o r o i d a l n e o v a s c u l a r i z a - acuity in Lbu right e y e w a s 2С УЗО a n d in lbe [etc e y e w as 20/200.
t i o n , J<ILl c h r o n i c p a p i l l e d e m a a s s o c i a t e d w i l h p s e u d o l u m o r N o te sw o lle n o p lic disc in b o th eyes ( A a n d tt) a n d lhe углу,
c e r e b r i , 1' ' ■l' 1 a n d c h o r i o r e t i n a l f o l d s f s e e C h a p t e r 4 ) . D i s c ly p e 2, Hubrt4infil p p q y a s O J lar m e m b ra n e iiim jw s , ]li e xle n d -
iпц te m p o ra lly from lh e Soil o p tic disc. F lq rte s c e Jfi й п ф й ф н рЬ Й
d r u s e n h a v e b e e n r e p o r t e d еп c h i l d r e n w i l h p rim a ry m e g a -
revealed e v id e n c e o f p e rfu s io n a n d staining o l (he neovascutar
c e p h a l y . ' 0' Drusen b o d ie s t)f lh e o p lic nerve head occur
m a n h r a n e Etfte™ fing Crtjn ■ lh e [ t v n w m l edge o f Lhe letL o p lic
c o m m o n l y , a n d th e re fo re m a n y a s s o c ia te d fin d in g s m a y b e
Hi sc and D ). X e n o n p h o to -c o a g u la tio n vras pFaced o v e r [he
c o i n c i d e n t a l . ' ..........l h e a s s o c i a t i o n o f d n i s e n a n d c h o r i o r e t i n a l area o f subrelinal n e o va sc u la riza tio n IE). N o t e lhal Ihe p h o to -
f o l d s p r o b a b l y is n o t c o i n c i d e n t a l . M o s t c h o r i o r e t i n a l f o l d s □oajjulation w a s n o l carried in lo the c e n te r o f ih e ioveaF area.
are p r o b a b l y a c q u i r e d a n d a re c a u s e d b y s o m e s u b c l i n ic a ! T v v u m o n lh s fo llo w in g p h o tO tQ a ^ u Ja tio n nole Ll-*! a tro p h y ol lh e
in fla m m a t o r y pro ce ss c a u s in g s h r in k in g a n d fla tte n in g o f
noli гм! p ig m e n t cpil helium Ibat estends into Hit; central m ac u la r
areg (F). The p a tie n ts visual a cu ity wish a p p fo x w la Le ly 6 /20 0 .
t h e p o s t e r i o r sc le ra , l h i s p ro c e s s a ls o c auses n a r r o w i n g o f
G - l : A c u t e o p tic n e u ro p a th y w ith d is c e d e m a , p e rip a p illa ry
Lh e o p lic c a n a l a n d in t u r n m a y p re d is p o s e th e o p tic n e rve
e x u d a tio n , a n d e iu d a liv e тл »си 1лг d e ta c h m e n t in iFw right e ye
h e a d io d ru s e n a c c u m u la tio n a n d o lh e r c o in p lic a tio n s su ch (C> o f a J l - y e a r - o l d m an c o m p la in in g o f ra p id loss o f v is io n .
as i s c h e m i c o p t i c n e u r o p a t h y a n d o b s t r u c t i o n o f t h e c e n t r a l H is lefl o p lic disc w as sm all a n d c o n ta in e d h ya lin e iio d kts
r e t in a l ve sse ls. I n s o m e p a t i e n l s h y a l i n e b o d i e s are i n h e r ­ harrow. H i . Tw o m o n th s later visual a c u ity bad im p ro v e d a n d
i t e d a s a n a u L o s o m a l - d o m i n a n t I r a i t . 1 !i 1■' '■" n 'J Fnyaline In d ie s w e r e e v id e n t in lh e rig h t d is c Ja iro w s , Ii.
K i u o r e s c c i n a n g i o g r a p h y is h e i p f u l in id e n t i fy i n g a lte r­ j a n d K : VisiFjIe t.a lc ifie d d ru s e n un Ihe d is c ыliгГчтес* in b o th
eyes o f a 5 t)-y o a i-o ld w o m a n .
a tio n s in th e n o r m a l o p lic n e r v e v a s c u la r p a tte r n as w e ll
as i n id e n t ify in g s u b r e lin a l n e o v a s c u la r iz a t io n a s s o c ia te d
w ith d ru s e n . i: fty v irtu e o f th e ir a u t o flu o r e s c e n c e ., s m a l l s c ie ra l c a n a l , c r o w d i n g o f n e r v e fib e rs , p a r tia l o p t i c

drusen n e a r th e s u rfa c e o f lh e o p t ic d is c c a n be d e te c te d a t r o p h y , e l e v a t e d d i s c m a r g i n s , c y t o id b o d i e s , d i l a t e d c a p ­

W i t h f u n d u s p h o t o g r a p h y u s in g a p p r o p r i a t e filte rs ( l i g u r e illa rie s , ju x ta p a p illa ry su b re tin a l hem orrhage, su b re tin a l

1 5 . 0 6 f :, G , ] , a n d K ). T h e a u Llio r has fo u n d th is t e c h n i q u e n e o v a s c u la riza tio n {H g u re l E i .0 7 R - E :), re tin a l s c a rrin g ,

h e lp fu l in d e le c tin g d ru se n lh a l w ere n o t v is ib le h io m i­ a nti c a lc ific a tio n . I lis to c h e m ic a lly (h e y are c o m p o s e d of

c r o s c o p i c a l l y . O C E ' is h e l p f u l i n m o n i t o r i n g t h e c h a n g e i n a m u c o p ro le in m a trix c o n ta in in g a c id m u c o p o ly saccha­

c o n t o u r o f th e d is c , w i t h c h a n g e s in th e s ize o r a n te rio r rid e s, rib o n u c le ic a c id , and o c c a s io n a lly i r m u 1^ 16 3 ,1* 3

m o v e m e n t o f t h e d n i s e n o v e r L i m e ( I 'i g u r e i 5 . 0 6 1 ] a n d I.J. T h e i r p a th o g e n e s is has been a sc rib e d lo K P IL m ig ra tio n ,

U l t r a s o n o g r a p h y is a ls o h e lp fu l in d e te c tin g o p t ic d is c h y a lin e d e g e n e ra tio n of Lhe n e u ro g lia , a c c u m u la tio n of

d r u s e n ., p a r t i c u l a r l y w h e n t h e y a re b u r i e d in a n o p t i c d is c d e g e n e ra tive p ro d u c ts o f a x o n s , a n d c o a le s c in g in tr a c e llu ­

th a t a p p e a r s n o r m a ! c lin ic a lly , o r in cases o f u n e x p l a i n e d l a r d e p o s i t s o f g l i a l c e l l s , - 11 i r a n s u d a t i v e v a s c u l o p a t b y , lf"

o p tic d is c s w e l l i n g . 1'4'1 f a i l u r e lo d e m o n s tra te c a lc ifie d and a xo p la s m ic tra n s p o rt a l l e r a t i o n s .1^ Jl is p ro b a b le

b o d ie s in th e o p tic nerve head o f in fa n ts and c h ild re n th at .1 c o n g e n ita l, a n d less c o m m o n l y a n a c q u ire d , s m a ll

w ilh a s w o lle n o p tic nerve head m ay not e xc lu d e th e o p t i c n e r v e s c l e r a l c a n a l l h a l is c r o w d e d w i l h n e r v e f i b e r s

presence o f d ru sen . It is p o s s i b l e , a llh o u g h not proven is r e s p o n s i b l e f o r a lo ca l d is tu r b a n c e o f a x o p l a s m i c tr a n s ­

h is lo p a lh o lo g ic a lly , lh a l d ru s e n m a y b e re la tive ly n o n c a l­ p o r t a n d d r u s e n f o r m a t i o n . L ' n- L - ' i s o f o u n d u E l r a s l r u c t u r a l

c ifie d h y a l i n e s tru c tu r e s i n y o u n g p a t i e n t s .'4" T h e c a lc ific a ­ e v i d e n c e to s u g g e s t t h a t o p t i c d is c d r u s e n are t h e r e s u lt o f

tio n c a u s e d b y d r u s e n a n le r io r to th e le ve l o f th e la m in a abnorm al in tra c e llu la r m e ta b o lis m and c a lc ific a tio n of

crib ro s a s h o u ld not be c o n fu s e d w ith th a l lo c a te d sev­ m i t o c h o n d r i a . - 4 '1 l h e m ito c h o n d ria are e x t r u d e d in to lh e

eral m illim e te rs p o s te rio r lo lh e la m in a c r ib r o s a '" '' The e xtra c e llu la r sp ace, w h e re th ey act as n id i fo r c o n Lin u e d

c a u s e o f t h i s l a t t e r f o c a l c a l c i f i c a t i o n is u n c e r t a i n . I n s o m e b u ild -u p o f ca lc ific d e p o s its . A c q u i r e d causes o f c h ro n ic

p a lie n ts lh e c a lc ific a tio n m ay be lo ca te d in t h e w a lls or c r o w d i n g o f t h e o p t i c n e r v e f i b e r s s u c h as i d i o p a t h i c c h o ­

E u n t e n o f t h e c e n t r a ! r e l i n a l a r t e r y , w h e r e il m a y d e v e l o p rio re tin a l f o l d s [se e C h a p t e r 4 ) a n d p s e u d o t u m o r ce rebri

as a d e g e n e r a t i v e c h a n g e i n a s s o c i a t i o n w i l h a l h e r o m a l o u s m a y a l s o b e a f a c L o r i n d r u s e n f o r m a t i o n . 1 " 2 :u ]

d i s e a s e , o r it m a y b e a c a lc ific e m b o l u s d e r iv e d f r o m th e The lo n g -le rm v is u a l p ro g n o s is fo r m o s t p a lie n ts w ith

a o r t i c v a l v e , 'i'h e s e EocaE r e l r o l a m i n a r c a l c i f i c a t i o n s i n a y b e d r u s e n o f l h e o p t i c d i s c is p r o b a b l y g o o d . I h o s e w i l h b u r ­

fo u n d in s o m e eyes w i t h c e n tra l re lin a l a rte ry o c c lu s io n . ie d d ru s e ii h a v e fe w e r v is u a l fie ld d e fe c ts t h a n t h o s e W it h

C o m p u te d lo m o g ra n h v fC E") is a l s o c a p a b l e o f d e t e c t i n g v i s i b l e d r u s e n . - ! ] -' V i s u a l fie ld d e fe c ts m ay show p rog res­

b u r i e d d r u s e n . 2* ^ - ™ " s io n in s o m e p a lie n ts . L ite n a t u r a l c o u r s e o f t h o s e p a l i e n t s

iiis lo p a th o lo g ic a lly , d rusen are c a lc ifie d e x tra c e llu - w ho d e v e lo p iu x La p a p iH a ry su b re tin a l n e o v a s c u la riza tio n

Ear b o d i e s l o c a t e d a n t e r i o r l o l h e l a m i n a c r i b r o s a ( l :i g u r e is v a r i a b l e , a n d s o m e p a t i e n l s m a y r e t a i n c e n l r a l v i s i o n i n

1 3.( J t D } .1 Lfi2' L ^ ■1lh?' 1 11 T h e y are a s s o c ia te d w ith s p ite o f p e r ip a p illa r y s u b re lin a l h e m o r r h a g e .

 'l h e b io m ic r o s c o p ic d ia g n tjs is o f d m s e n o f t h e o p tic d is c I S . ОЙ Fam ilial o p tic n e u r o p a t h y .
is r e l a t i v e l y s e c u r e i f t h e c a l c i f i e d b o d i e s a r e v i s i b l e u i l h i n t h e
A : "Ibis youn^ |^irl had mi 3d visual loss ап-d л cecocenHa I
e le va te d o p lic n e rv e h e a d . O c c a s io n a lly n o n c a lc ifie d d m s e n - scotoma in both eyes. H e r sibling had similar findings. Note
l i k e c h a n g e s nine c a u s e d b y p a p i l l e d e m a . ' 1^ Eh e d iffe re n tia l lhe sefji r-enta I area o f opjlic alrophy temporally,
d ia g n o sis of jiu ta p ^ ilJa iy c h o ro id a l n e O T a s c trla jiis tio J» tt: This 4(J-yea r-ol [J lama ican man had poor vision in his lefl
a s s o c ia te d w i l h a s w o lle n o p l i c d is c in c lu d e s lh e p r e s u m e d eye since sustaining Irauma Co I ha I eye aL 30 years of аду. He
o c u la r h is to p la s m o s is s y n d r o m e , a n g io id stre aks, id io p a t h ic
was- asymplnmatic in (he Tiji.hr eve bul was rt'fermd lirecause
his best corrected vision in (be eye was 20/70. There was a
c h o r o id a l n e o v a s c u la r iz a tio n . s a rc o id o s is , p a p ille d e m a w i t h
wedge-shaped area a t LemporaE pallor in both oplic discs
p s e u d o t u m o r c e r e b r i, a n d c o n g e n i t a l p it o f t h e o p t i c d isc .
iBi and pusnraLrmatic scarring in [he lefl m acula. He bad
hi lateral oacocenlraJ stolon da la. II is prohahle that a familial
HEREDITARY O P T I C oplic alrophy that developed in early childhood was respon­
sible for subnormal acuity in the ri^ht eve.
NEURO PATHIES______________________ C-F: D o m in a n t optic atro p h y a ffe c te d lo U r generations оI lh e
family o f this 3-year-old Егюу 1C a n d O ) .infI his 2 5 -year-old
lh e h e r e d o d e g e n e r a l i v e o p Lie n e u r o p a t h i e s m u s t be c o n ­
father (Ё an d F>. T h e son's visual acuity w a s 20/40 hi laterally.
s id e r e d i n p a tie n ts w i t h i n s i d i o u s as w e ll as r a p id lo ss o f
T he father y a v e a history ot slow loss, o f v is io n since c h ild -
c e n tra l v is io n . h o tjd . 3-lisvisLf.il acuily was 20/200 in b o lb eves.
'■
■■-L: Dominanl oplic atrophy affecting three generalions of
this family. Kfroband is a 12-year-old boy with 20/50 vision
Dominant Optic Atrophy (KjerTypej
in each eye. Bolh optic discs showed temporal pallor (G and
P a tie n ts w ilh d o m in a n t o p tic a tr o p h y n o te Lhe in s id io u s H and he bad bilateral tenLrocedaE scotomas. on visual field
onset о Г m ild ly p ro g re ss ive lo ss o f v is u a l a c u ity, u s u a lly testing. Optical coherence tomography through both macuEas
b e g i n n i n g b e f o r e 1 0 y e a r s o f a g e ^ 2 l J " 2jW V i s u a l l o s s is b i l a t ­
showed normal pholorecepflors, bul mild thinn-in^ of the nasal
inner retina fH and 12 arrows). His -15 -year-old falher was
eral b u t m a y b e a s y m m e tric . M any p a t i e n l s are u n a b l e l o
asymptomatic with 20''20 vision in bolb eyes (I). His 74-ytM.r-
re call Lhe L i m e o f o u s e l o f Lhe d is e a s e , a n d s o m e m a y b e
old paterms] grandfather compfairied of slow loss of vision,
a s y m p to m a tic . A lth o u g h t h e o p t i c a t r o p h y is d o m i n a n t l y never corredaEjle beyond 20/40 for Ibe previous 30-plus
in h e rite d , a p o s itive fa m ily h is to ry m a y n o t he o b ta in e d years., and had temporal pa11or of berth optic discs ■
:K. L).
( E 'ig u r e 1 5 .0 Й } . lu te rfa m ilia l and in lra fa m ilia l v a ria tio n s
in a c u it y lo ss m a y o c c u r [r a n g e : 2 0 / 3 0 - 2 0 / 4 0 0 ] . T h e c h a r ­
a c t e r i s t i c f i e l d d e f e c t is a c e c o c e n l r a l s c o t o m a . D e p r e s s i o n
o f th e t e m p o r a l is o p le rs m a y s im u la te a b i t e m p o r a l h e m i -
a n o p ia . C o n s t ric tio n o f p e rip h e ra l i s o p l e r s is r a r e . I'M t a n lh e OPAJ (o p tic a tro p h y typ e 1] gene is lo c a lis e d
( b l u e ) d y s c h r o m a l o p s i a is t h e c h a r a c t e r i s t i c c o l o r d e f e c t i n Lo a 1 .4 - c M in te rv a l on ch ro m osom e ^ Ц $ & с £ 2 & , а:12~235
d o m in a n t o p tic a tro p h y . A g e n e r a liz e d d y s c h r o m a lo p s ia .. M is s e n s e , nonsense, d e le tio n f r a m e s h i ft and sp lic e s ite
how ever, m ay be p r e s e n t in som e cases. T e m p o r a l o p lic a lte ra tio n s a c c o u n lin g fo r m o re th a n 100 m u ta tio n s have
d isc p a l lo r , o f t e n w i t h a tria n g u la r area o f te m p o r a l e x c a ­ been seen in v a rio u s p e d ig re e s o f p a tie n ts w ilh d o m i­
v a tio n . is c h a r a c t e r i s t i c ( E 'ig u r e 1 5 .O S A and II]. A l t h o u g h n a n t o p tic a lro p h y . i h i s e x p la in s th e h e te r o g e n e ity o f th e
u n c e rta in tie s re m a in c o n c e r n in g th e p a th o g e n e s is o f th e p a th o p h y s io lo g y o f th e d is e a s e and th e va ria b le pheno­
fre q u e n tly e n c o u n te re d W est In d ia n o p tic a tro p h y, it i s typ e (fig u re 1 5 .0 8 G ;-E .j. T h e p e n e tra n c e o f th e g e n e v a r ­
p r o b a b l e t h a t m a n y cases a re e x a m p l e s o f d o m i n a n t o p l i c ies f r o m 43 t o В Э Ч Ь ^ 2 2 6 - " 26 El is l i k e l y t h a t e n v i r o n m e n t a l
a tro p h y (H g u re 1 5 .0 & B and Cj see d is c u s s io n o f n u tri­ fa cto rs a ls o p l a y a r o le i n d is e a s e s e v e rity in s u s c e p tib le
tio n a l a m b ly o p ia b e lo w ). in d iv id u a ls , lh e O P A l p ro te in is a n c h o r e d to th e m it o ­
W e ie b e r a n d M iya k e d e s c rib e d fa m ilia l o p lic a tro p h y c h o n d ria l cris ta te in n e r m e m brane and is b e lie v e d to
a s s o c ia te d w i t h " n e g a t i v e ' ,T e Ie c l r o r e l i n o g r a m s i n t w o f a m i ­ prevent c yto c h ro m e с re le ase fro m m ito c h o n d ria and
lies w i l h lo s s o f c e n tr a l v i s i o n o c c u r r i n g i n t h e s e c o n d a n d b lo c k o rg a n e lle fra g m e n ta tio n , th u s p ro te c tin g th e ce lls
t h i r d d e c a d e s o f life , o p t i c a t r o p h y , d e f e c t i v e c o l o r v i s i o n , fro m a p o p t o s i s . - ^ - 2 - ■'- w !t is l i k e l y t h e r e a r e o L h e r h i t h ­
m ild lo m o d e ra te m y o p ia , and p e ric e n tra l or c e n lra l e rto u n k n o w n g e n e d e fe c ts th a t a c c o u n L fo r s o m e cases o f
s c o t o m a s .--1 d o m in a n l o p tic a tro p h y .
f-irrcrfitnry L>f3kf£f tvcit.Tvpn{&jcs 12/3
Leber's Hereditary Optic Neuropathy 1Ъ. L e b e r ' s o p lic n e u ro p a th y.

L e b e r 's h e re d ita ry optic n e u ro p a th y [LI L O N ) is а m a t e r ­

A —D : O n e y e a r p r e v io u s t y Ibis lf l - y e a r - o l d m a n d e v e l o p e d
b lu rre d v is io n in lh e rigbl e ye . The diiaynosis Hi that lim e w a s
n a lly in h e rite d d ise a se th at is c h a ra c te rize d by a cute ,
re lro b uEba r n e uritis . N e u r o l o g i c e v a In a tio n w a s n e g a tiv e . H e
severe, b ila te ra l v is u a l to ss in h e a lth y young p erson s
gave a 2 - w e e k hislory ol b!i.irjed v is io n in lhe left L y e . Visu a l
(15 -3 5 y e a r s ) , u s u a l l y m a l e s ^ 0 - ^ 0 % ) , 2 3 1 - - лэ l h e visu a l n cu ily in th e right e v e wiis b /2 0 0 a n d in I b e lel’L e y e w h s
Lo ts c a n o c c u r in younger and o ld e r in d iv id u a ls and (.Lie 2 0 / 3 0 0 . T h e r e w a s segm enta l a t r o p h y o l the right o p L k disc.
a g e r a n g e o f o n s e t Is. 2 - S O y e a r s . J h is v a r i a b i l i t y o f a g e a l T h e re w a s telangiectasis a n d LorLuosity o f [he capilEaries o f
onset can occur Щ m em bers of th e sam e fa m ily ""1 137 Lhe Eeft o p t i c d isc a n d ju x t a p a p illa r y retina [A !1. A n g i o g r a p h y
l h e c e n t r a l v i s u a l l o s s is a c u t e o r s u b a c u t e a t o n s e t p a i n ­ d e m o n s tra te d Lhe pa tte rn o! ihese abnorn-jal vessel? la rr o w s ,
В ■, whi< !i sh o w e r] n o e v i d e n c e o f fate si a i r i n g I f !1. F o u r t e e n
less, a n d a c c o m p a n i e d b y la r g e c e c o c e n t r a l s c o l o m a L a a n d
yeEirs 3aLer visual a c u it y in the riyht awe whs 2 0 / 4 0 0 a n d in
d y s r h r o m a t o p s ia . C e n tr a l v is io n d e te rio ra te s p ro g re s s iv e ly
Lhe left e y e w a s 2 0 / 2 0 0 . B o th aplrc discs s h o w e d te m p o ra l
first i n o n e e y e t h e n i n t h e o t h e r , t y p i c a l l y w i t h a n i n t e r v a l ра11<н i.D j. T h e te la n g ie ctatic vessels w e j e less ^ b p a re r fc
o f d a y s t o w e e k s . I n t e r v a l s o f a s l o n g as 1 2 y e a r s h a v e b e e n 1: ,in d F : А 2 8 -y e a r - o k l n u n w i l h a c u le Leb er's o p tic n e u r o p -

r e p o r t e d . - ' ’ '' T r a n s i e n t w o r s e n i n g w i l h e x e r c i s e o r w a n n i n g , aLhy. N o t e Eiie te la n g ie c ta tic tortu ous reLinal vessels -arrows?.
as o c c u r s i n o t h e r o p t i c n e u r o p a t h i e s ( L J b l h o f T s s y m p t o m ) , T b is- 1 4 -y e a r -o ld Езоу, w i t h a f a m ily history ot L e b e r ^
m a y o c c u r .J ' A ll le vels o f v is u a l a m i t y lo ss h a v e b e e n
o p lic j * * k o p a t h y f pre s e n te d Е)ес,шне o f rapid loss o f v is io n o f
2 w e e k s ' d u r a t io n . A t age 1 2 years his vis u al a c u it y w a s 2 0 /2 0
re p o rte d ra n g in g fro m no lig h t 20 / 20 , b u t
p e rc e p tio n to
a n d g e n e tic analysis o f his b l o o d was positive lor Leb er's d is­
it c o m m o n l y d e c l i n e s t o L e v e l s w o r s e t h a n 20/200 b i l a t e r ­
ease. H i s visual a c u it y a I Lhe tim e o f these p h o to g ra p h s w h s
a lly , u s u a lly o v e r s e v e r a l w e e k s t o s e v e r a l m o n t h s .'1 2 0 /2 0 0 in Lhe right e y e a n d 9 /20 0 left e ye . T h e right opLLc disc
A lth o u g h th es e p a tie n ts are t y p i c a l l y b e t w e e n t h e ag es o f was liy p e re m ic (G jr lhe left o p L k disc s h o w e d lem p o ra l p a l­
IS a n d 3 0 y e a rs a t o n s e t, v is u a l lo ss m a y n o t o c c u r u n til lor. l h e r e was general Ii z e d lorluosity o f the relinal vuins. N o t e
th e s ix th d e c a d e o r b e y o n d , w h e n th e c lin ic a l p ic tu re m a y the d ilation a n d lo rlu o s ity o f the small ju ^ La -p a p illa ry vcmules
be m is ta k e n fo r A l O N JZie'J ‘t2-245 C o lo r vis io n is a f f e c t e d (arrows, H j . Several m o n t h s later b o l h o p t i c d i s a s h o w e d
te m p o ra l p a llo r i.3 a n d J.i a n d the visual a c u ity w a s J / 2 0 0 .
e a r l y a m i v i s u a l lie I d e x a m i n a t i o n r e v e a l s a c e n t r a l o r c e c o -
К a n d L : O p E i c a t r o p h y in L w o siblings o f Lhe patient illus­
e e n tra l s c o t o m a . ' l l i o m i c r o s c o p y re ve a ls c ii c u n i p a p i l-
trated in C - J .
Eary t e la n g ie c t a t ic m i c r o a n g i o p a l h y , s w e llin g o f th e oerve
fib e r laye r a r o u n d th e d is c ( p s e u d o - e d e m a ) , a n d absence o f in c lu d e m ovem ent d is o rd e rs , s p a stic ity, p s y c h ia tric d is tu r­
flu o re s c e in le ak ag e (H ig u ie ] 5 . Q 5).ilQ-1Ji-247 M o s t p a tie n ts bances, sk e le ta l a b n o rm a l!tie s ., acute in fa n tile encepba-
s h o ^ ' n o im p r o v e m e n t b u t p a rtia l o r e v e n c o m p le te recov­ lo p a lh ic e p is o d e s , d ys to n ia * Le ig h -lik e e n c e p h a lo p a th y ,
e ry m a y o c c u r !>-10 y e a r s a f t e r o n s e t o f v i s u a l l o s s ^58^3*051 p e r i a q u e d u c t a l s y n d r o m e , a n d d e m y e l i n a t i n g d is e a s e r e s e m ­
Ln viro n m e n ta J trig g e rs s u c h as s m o k i n g , i r a u m a , hum an b lin g m u l t i p l e s c l e r o s i s . - l'!' A s im ila r o p tic n e u ro p a th y has
im m u n o d e fic ie n c y viru s (H IV ) in fe c tio n can p re c ip ita te b e e n r e p o r t e d w i l h s k e le ta l a b n o r m a l i t i e s ,- " ' a n d in a s s o c ia ­
o n s e l o f v i s u a l loss in s u s c e p t ib le i n d i v i d u a l s c a r r y i n g th e tio n w ilh C h a r c o t - M a r i e - I d o t h ( C M T ) d is e a s e , a h e n e d it a r y
g e n e tic d e fe c t.i , u 5 D ila tio n o f th e o p tic n erve s h e a th s d ise a se o f p e r ip h e r a l nerves in al least i w o f a m i l i e s . ^ ' - 1‘-'A
w ilh c e re b ro s p in a l flu id h as b e e n d e m o n s tra te d by u ltra ­ U e m u r a a n d c o w o rk e r s h ave Id e n tifie d m ild b u t d is tin c t b i o ­
sonography (3 0 c test) and h is to p a tb rfflg ia lfe ^ ^ 5 c h e m ic a l a n d e le c tro n m ic r o s c o p ic c h a n g e s m m u s c le b io p s y
P a t h o l o g y o f t h e r e t i n a a n d o p t i c n e r v e is a v a i l a b l e o n l y f o r in p a tie n ts W ith l . E I O N .-'"1 W a l l a c e a n d o th e rs , in 1 У Д З , id e n ­
la te -sta g e d is e a s e . G a n g l i o n ce ll a tr o p h y , e x c a v a t io n o f th e tified a m ito c h o n d ria l re p la c e m e n t m u ta tio n in n in e o f II
o p t ic d is c c u p fille d w i t h g lia l a n d c o n n e c t iv e tissu e , a n d fa m ilie s w il h m e m b e r s d ia g n o s e d w i l h L H O N .2*4
s y m m e tr ic d e s tru c tio n o f th e m y e lin sh e a th s in th e o p tic W hen I.H O N a p p e a r s f o r th e firs t t i m e in a fa m ily , th e
nerve tra n s m ittin g p a p illo m a c u la r b u n d le fib e rs are th e d ia g n o s is is o f t e n d e l a y e d o r m is s e d , in t h e a c u le stag e,
fin d in g s w it h in th e eye. lh e o p tic c h ia s m and tra cts a ls o c irc u m p a p illa ry te la n g ie c ta tic m ic ro a n g io p a lh y , s w e llin g
s h o w e d lo ss o f m y e l i n s h e a t h s a n d a x is c y l i n d e r s c e n t r a l l y o f th e nerve fib e r laye r aroun d lh e o p tic d is c (p s e u d o ­
w i l h re la tiv e p r e s e r v a t i o n o f p e r i p h e r a l fib e rs . S h r i v e l e d lat­ e d e m a ), and a b se n ce o f s ta in in g on flu o re s c e in a n g io g ­
e ral g e n ic u la te b o d ie s a n d d e m y e l i n a t i o n o f th e o p t ic ra d ia ­ r a p h y are c h a ra c te ris tic (fig u re s (5 .0 U and 1 ! > . 10 И ) . ‘ " ’ •-w
t i o n s s u g g e s t t r a n s s y n a p t i c d e g e n e r a t i o n - r'-' P ro g re s s ive e n la r g e m e n t o f th e b l i n d s p o t u n til it r e a c h e s
V i s u a l d y s f u n c t i o n is t h e o n l y m a n i f e s t a t i o n o f L H O N in fixa tio n c h a ra c te rize s lh e e a rly p ro g re s s io n o f fie ld lo ss.
m o s t p a tie n ts . A l t h o u g h o t h e r n e u r o l o g i c d is o r d e r s are o c c a ­ M a n y a s y m p lo m a Lic fa m ily m e m b e rs w ilh Ije b e r 's d is e a s e
s io n a lly re p o rte d ( L I - I O N " p l u s " ) , l h e b e s l - e s t a b l i s h e d l i n k is have p e rip a p illa ry m i e r o a n g i o p a L b y . 241^ * ' - ^ rr h e s e vas­
b e tw e e n 1 J I O . N a n d c a rd ia c c o n d u c t i o n a b n o r m a lit ie s . ' c u la r c h a n g e s m a y be e v id e n t a n g io g r a p h io a lly a n d occur
W o lfF -P a rk in s o u -W h ile and Ijo w n -G a n o o g -Le v in e are th e years b e fo re th e a c u te phase o f th e d i s e a s e .-'*'1 lh e y
m ost co m m on a s s o c ia tio n s [9 % ). P ro lo n g e d Q T in te rva l, in c lu d e p ro g re s s ive a rte rio v e n o u s s h u n tin g lh a l sta rts i n
s y n c o p e , p a lp ita tio n s , a n d s u d d e n d e a t h are s e e n o c c a s i o n ­ th e i n f e r i o r a rc u a le n e r v e fib e rs a n d th a t m a y b e a s s o c ia Le d
a lly . M in o t n e u ro lo g ic a l a s s o c ia tio n s in c lu d e exag g e rate d o c c a s i o n a l l y w i t h p r e r e tin a l h e m o r r h a g e s . A c u t e v is u a l lo ss
re fle xe s, m y o c l o n u s , se izu re s, m u s c le w a s t i n g , s e n s o r y a c id is a c c o m p a n i e d b y d i l a t i o n o f t h e b r a n c h e s o f t h e c e n t r a l
a u d i t o r y n e u r o p a t h y , a n d m i g r a i n e .M o re se ve re a s s o c ia tio n s re tin a l a rte ry and p e rip a p illa ry te la n g ie c ta tic c a p illa rie s .
f-irrcrfitnry L>f3kf£f tvcit.Tvpn{&jcs I2 О
T h e s e ch a n g e s d is a p p e a r ль a tro p h y o f the o p lic f f ir t e \5 .1 0 L e b e r's h e r e d t a r y o p tic n e u ro p a th y .
d e v e lo p s f i g u r e I 5 .0 5 D ) . LlnELkt' d o m in a n l o p tic atro p h y,
Л -C: A 2 C-year-old otherwise heallhy man who hnd painless
the a tro p h y often p r o g r e s s to in v o lv e the e n tire o p lic lost o f vision in his lefl eye Lo 20/100. Vision in thu i ij^h: S v e
d isc. R etin a l arterial n a rro w in g a n d in crea sed c ir c u la lio n was 20/20. Red free p h o tog rap h and i luonuscei n an^io^ram
Lime occur. A n g io g ra p h y it p ro b a b ly u se fu l in e x clu d in g show 1elan$"ieclasia of smalf vessels around [he disc (arrawsf.
Leb er's d isea se in a sy m p to m a tic in d iv id u a ls .4'" A cq u ire d O ptical coherence tomography o f the lefl eye shows thick­
re d -g re e n d e fic ie n c y ch a ra c te rize d b y a d e u la n -lik e dis- ened uTiefve fiber layer-pst'udoudc'rna'' compared Iо the
right eye and is outside the normal ranye. His maternal male
c r im illa t io n d efect is ch a ra c te ristic acid m a y be d e le cte d in
cousins had unexplained loss of vision and he had a genetic
s o m e a sy m p to m a tic ca rrie rs. L le cL ro re tin o g ra p h y a n d d a rk
mitochondrial point mulaLion at 1177Й.
a d a p ta tio n are u s u a lly n o rm a ] in these p a tie n ts.” " V isu a l
l''^ tvp k 'alb .1 li 11!x-_ s Sin iEi .:, I ! lT i i n s c l. lu ll м и н ' p atien ts L e b e r's id io p a th ic ste lla te n e u r o re tin itis .

m a y sh o w e ith e r im p ro v e m e n t o r w o rs e n ing. '['here it n o 1} ,ind t: A 33-year-old wom an cteveluped blurred vision in

lhe ri^hl eye E 1 days afler an episode ol headaches, vom ­
effective trea tm en t fo r th e disease. S in c e th e p rim a ry lo c u s
iting, and diarrhea. Note* lhe oval, yelldsfosh exudate in lhe
o f the d ise a se a p p ea rs to be in the in tra o c u la r ra th e r than
□enter o f the m acula and lire fine m acular star, which is
the re tro b u lb a r area, Leb er's h e re d ita ry v a s c u la r n e u ro ­ more prxflpinent nasally lhaii temporally :Г)1. There ]s some
re tin o p a th y has been su g g e ste d as a m o re a p p r o p r i a t e exudative detachment oE the peripapillary retina. The left fun­
n a m e . ' '' L U O N is s t r i c t l y m a te rn a lly in h e rite d a n d p a s s e s dus was normal. Angiography showed definite leakage of dye
lo fu tu re g e n e ra tio n s o n ly th ro u g h wom en. A n a ffe c te d from lhe oplic disc and no Evidence of abnorm ality in the
m a le n e v e r h a s a ffe c te d o ffs p r in g , w h e re a s a w o m a n m ay m acular area (E)- Aflg^ogjaphy of lhe left eye was normal.
F and G : This Sl-year-oid man gave a 1-month history of
have a ffe c te d c h ild r e n a lth o u g h she h e rs e lf is v is u a lly
decreased vision in his Left eye. Vi-suaC acuity w a s 20/50.
n o rm a l.
Note (he faint yellowish material in (he center of the m acula
I.H O N is a s s o c i a t e d w i t h f o u r d i f f e r e n t p o i n t [ n u t a t i o n s
anti the macular star, which is more prominent nasally IFj.
o f m ito c h o n d ria l D M A th a t a p p e a r to be p a th o g e n e tic fo r The oplic disc is w ilhin normal limits. Angiography of lhe
th e d is e a s e .u 1 24 ^ i m - i ? : Thesf ^ u tilio n s a ffe c t right eye was normal. Anjjio|jraphy of Lhe left eye (G) showed
n u c le o tid e p o s itio n s 1177Ё, 144Д 4, i? 4 6 0 , and 15 25 7 marked fluorescence of the optfc d]sc.
a n d are lo c a t e d w i t h i n t h e g e n e s t h a t c o d e f o r p r o t e i n s in
th e c o m p le x E o f th e re s p ira to ry c h a in . T h e c lin ic a l fin d ­
in g s are s im ila r, e x c e p t Lh ai p a tie n ts w ilh 14484 are m o r e
liv e ly Lo e xp e rie n c e v is u a l reco ve ry th a n p a tie n ts w ilh va ria b ility o f e xp re s s io n o f th e d ise a se in fa m ily m em ­

th e o th e r th re e m u t a t i o n s . ' '' P a tie n ts w ith 15257, w ho bers. A p p ro x im a te ly 2U % o f m en and 4 % of w om en

a ls o h a v e a n a s s o c ia te d m u ta tio n al 15 8 12 , are less l i k e l y e xp e rie n c e d v is u a l loss in an A u s tra lia n s tu d y w h ere a

Lo r e c o v e r v i s i o n th a n th ose w ith o u t th is a s s o c ia tio n ." '^ d ra m a tic d e c lin e in Lhe p e n e tra n c e o f th e d is e a s e has

P a tie n ts w ith th e 1 5 2 5 7 m u ta tio n a ls o h a v e a h i g h e r i n c i ­ been n o te d /1 T h e r e fo r e , s u c c e s s fu l d e te rm in a tio n of

d e n c e o f s p in a l c o rd a n d p e rip h e ra l n e u ro lo g ic s y m p t o m s th e m ito c h o n d ria l U N A g e n o typ e o f a fa m ily o r p a tie n t

th a n p a tie n ts w it h th e o t h e r m u ta tio n s . M o le c u la r g e n e lic w ith L H O N re q u ire s te s tin g o f m ore th a n one fa m ­

t e s t i n g is o f p r a c t i c a l v a l u e i n c o n f i r m i n g t h e d i a g n o s i s o f ily m em ber and m ore th a n one tis s u e fro m each in d i­

a ty p ic a l cases o r in p a tie n ts p r e s e n t in g w i t h o p l i c a l r o p h y , v i d u a l . J? ] M o le c u la r g e n e tic te sts are 10t№h sp e c ific bul

in lhe a b s e n c e o f a f a m i l y h i s t o r y , a n d a f t e r t h e c h a r a c ­ o n ly 50% s e n s itive fo r th e d ia g n o s is o f L H O N . it m ay

t e r i s t i c t e l a n g i e c t a s i s is n o l o n g e r e v i d e n t . 2 ?C}," 7S ' I h e p r o ­ be p r u d e til l o a d vis e c a rrie rs to a v o id exposu re lo to x­

p o rtio n of m u ta n t m ito c h o n d ria ] D N A m o le c u le s was in s such as t o b a c c o sm oke and e xce ssive a lc o h o l in ta k e

fo u n d to s h ift m a rk e d ly across g e n e ra tio n s and w ith in s in c e th e y m a y fu rth e r c o m p r o m is e m ito c h o n d r ia l e n e rg y

tissu e s o f a n i n d i v i d u a l ( h e t e r o p l a s m y ) . i h is e x p la in s th e m e l a b o i t s m . j r ,0 '2:j'
Leber's Idiopathic Stellate Neuroretinitrs E5.M'i C o n t i n u e d

and Multifocal Retinitis (See Chapter 10) H —|: This 29-year-old гпдп noled fever, nausea, vnmilinj^
nitd rapid loss cjf vision in Lhe lefl eye o f 2 daW^ duraLion.
in ] ^16 I h e o d o r L e b e r d e s c r i b e d t h e c l i n i c al s y n d r o m e c h a r ­ He admitted sleeping w ilh cats. His visuaE acuily W as 20/30
a c t e r i s e d b y u n i l a t e r a l l o s s af" v i s i o n , o p t i c d i s c s w e l l i n g , m a c ­ rigjit eye and 20/300 lefl eye. Note (E>e peripapillary local
u l a r sta r, a n d s p o n t a n e o u s r e s o l u t i o n o f u n k n o w n cause in атеа5 of roLin ili-s ii> l>och uyes larrows, H ar>d I) and lhe swol­
o th e rw is e h e a lth y p a t i e n t (fig u re s 1 5 .1 0 0 - L a n d 1 5 . ] l ) . JJijl len leit optic disc fl). Four days Later Lie had developed a
m acular star (Jl. His Liter for Kochaltm aea was posilive 1:20.
! n h v o - t h i r d s o f lh e p a l i e n t s s e e n a t the L S a s c o m l ^ t l m e r Eiye
He was treated w ith doxycycEine, 1DOm# tid, Ibr 2 weeks.
I n s t i t u t e , a v i r a l - l i k e i l l n e s s h a s p r e c e d e d the o n s e t a f s y m p -
I w o months laler his vinual acuity w as 20/20 bilaterally.
t b E p i ; ^ ' 333- 3^ ' i n m o s t p a l i e n l s l h e v i s u a l a c u i l y r a n g e s f r o m
К and L : Swollen o plic disc and macular star in a 19-year-
2 0 ,■ 5 0 t o 2 0 / 2 С Ю a n d a n a f f e r e n t p u p i l l a r y d e f e c t is p r e s e n t . o]d man com plaining o f recent Loss o f vision in the riyhl eye
l/ tu r in g t h e first w e e k a f le r t h e o n s e t o f s y m p t o m s , th e m a c u ­ Lhal Еге^лгт 1 week nfler Ihe onset o1 an upper respiralory
l a r s t a r is u s u a l l y p r e c e d e ; ! b y m i l d s w e l l i n g o f l h e o p l i c d i s c infecllon. Visual acuily was 20/200. H ie lefl eye was normal.
a n d p e r i p a p i l l a r y e x u d a t i v e d e l a c h m e n L o f t h e r e t i n a ( E 'ig u r e s M edical evalualion wan negative. ^i\ years I ale* Ihe fundus
1 5 .I 0 D , J, К and 1 5 . 3 1A and [n д ^
was normal. Visual acuily was 20/25.

p a Lie n ts th e s w e llin g o f th e d is c m a y b e m o r e m a r k e d a n d m a y ,V ( . lourlihj-- :>l I Jr. M. l.i'Kf НИ,-1i.'

b e a sso c ia te d w i l h s p lin te r h e m o r r h a g e s . O n e o r m o r e focal
w h i l e re tin a l le s io n s m a y o c c u r ( f i g u r e s 1 5 .3 0 ] E - | a n d 1 5 .1 1 E
and I-L J .-P 5-™3'28 ]h e se focal areas o f r e tin itis m яу
c a u s e o c c l u s i o n o f e i t h e r a b r a n c h r e t i n a l a r t e r y o r a v e ±^204 j,Jn
i n s o m e p a t i e n t s t h e m u l t i f o c a l r e t i n i t i s Ls n o t a s s o c i a t e d w i t h
o p t i c d is c i n v o l v e m e n t . V i t r e o u s cells are p re s e n t in 9 0 % of and C L ) . - ," " - ih 1 Som e 10 -15 % o f p a tie n ts m a y s h o w m ild
C a i a t JS3 A n t e r i o r u v e i t i s is p r e s e n t i n a f e w p a t i e n t s . W i t h i n le a k a g e o f dye fro m th e o p tic d isc in th e o p p o s ite eye
several d a y s o r ^veeks, th e p e r i p a p il l a r y e x u d a te b e g in s to s u b ­ (fig u re 1 5 .]1 L > ) . fo c a l w h ile re tin a l le s io n s , if presen t,
sid e a n d a m a c u l a r star a p p e a r s a n d b e c o m e s m o r e p r o m i ­ u s u a lly s h o w e vid e n c e o f s ta in in g (fig u r e EБ. 111] and I).
n e n t as t h e d i s c a n d p e r i p a p i l l a r y s w e l l i n g d i s a p p e a r s ( ] : E g u r e A n g io g ra p h y shows no a b n o rm a lity o f c a p illa iy r p e r m e ­
1 5 . 10b a n d w i t h i n th e fu st several w e e k s th e v is u a l a b i l i t y i n t h e a r e a o f t h e m a c u l a r s t a r . It m a y d e m o n s t r a t e
a c u i t y b e g i n s l o i m p r o v e , a n d w i t h a f e w e x c e p t i o n s it e v e n ­ a m ild w in d o w d e fe c t in th e R F E p a rtic u la rly in th o s e
t u a lly re tu r n s t o n o r m a l , l h e m a c u la r star u s u a l ly d is a p p e a rs p a t ie n t s f o l l o w i n g r e s o l u t i o n o f a p r o m i n e n t m a c u l a r star.
w ith in 6-12 m o n t h s . A fe w p a tie n ts m a y b e le ft w i l h m i l d paE- J.o s s o f v is u a l fu n c tio n p r i m a r i l y re su lts fro m changes in
lo r o f Lhe o p l i c d is c a n d m i l d p i g m e n t a r y c h a n g e s in th e c e n te r th e o p tic nerve head and not th e m a c u la . La b o ra to ry
o f th e m a c u la , E h e fo ca l areas o f re tin itis re s o lv e s p o n t a n e ­ in ve s tig a tio n s d o n e a l th e tim e o f v is u a l lo ss a re u s u a lly
o u s ly , u s u a lly w i t h i n several u e e k s . n o rm a l. P a tie n ls m ay show m ild s p in a l flu id p Ee o c y lo s is
flu o re s c e in a n g io g ra p h y shows e vid e n c e o f abno r­ (fig u re 1 5 .1 1E -1).
m al c a p illa ry p e rm e a b ility , p a rtic u la rly fr o m th e c a p illa r­ T h e re is e n o u g h e v id e n ce that caL-scralch d isea se is
ies d e e p w ith in th e o p t ic d is c , n o l o n l y d u r i n g th e e a rly o n e o f th e ca u se s o f th is i y n d r o m e 2lCL3* 3-2ei,rJ,‘l'29b"*m (see
phase o f th e d is e a s e (H g u re 1 5 .1 0 B ) but even a fte r th e c h a p t e r 10J. in one p atie n t, Leptospira o rg a n ism s w ere c u l­
d i s c h a s r e l u m e d t o its n o r m a l a p p e a r a n c e ( f i g u r e ] 5 . 10E-' tured from the s p in a l flu id .
H i'm fjfn jv O ptic Ncurcfpattucs 1,279
 H i s t o p j t h t ) 1 o | l c a [ ly, t h e m a c u l a r s t a r is c a u s e d b y th e 15 -. M L e b e r 's i d i o p a f h i с s l e I J a l e n e u r o r e l i n i t is

m i c r o g l i a l L iig .e b tlo n o f t h e l i p i d - r i c h e x u d a t e l y i n g in ( h e w ith a n g io g ra p h ic e v id e n c e o f in v o lv e m e n t o f lh e

o u te r p le x ifo rm l a y e r o f H e n It’ . N g u r e 1 5 .П М d e p ic ts d i a ­ a s y m p to m a tic e ye ,

g ra m m a tic a l! у lh e p ro b a b le p a th o g e n e s is of a m a c u la r A -D : This 9-year^JbJd girl noted nap id Josh of vision in lhe

star. A p r o t e i n - a n d l i p i d - r i c h e x u d a t e l e a k s f r o m th e c a p il­ right eye. Note the marjular star and slight swelling and pal­
la rie s i n th e d e p t h o f lh e o p tic d is c a n d e x le n d s b e n e a th lor of lhe opt if iiisc (Л:. Thy LefL fundii* appeared потппа! :HS:.
th e re tin a in th e p e rip a p illa ry re g io n as w e ll as a lo n g Visunl acuity was in (ho right Eye and 20S2Q in Lhe?
Lhe p la n e o f d ie o u te r p le x ifo rm la ye r i n l o th e m a c u la r
EefL eye. Angiography revealed staining ol the temporal half
0 I the right optic disc (Cl and the superonasal quadrant of
r e g io n ." " W ilh re a b s o rp tio n o f th e se ro u s c o m p o n e n t
Lhe left opLicdisc (b).
o f th e e x u d a le in th e m a c u la r re g io n th e lip id a n d p ro te in
E—I: This- Ы -year-old f^irl had a hislory of an upper respiratory
p re c ip ita te in th e o u te r p k x i f o r m la ye r a n d are e n g u lfe d b y infection be lore the unset of visual loss in Lhe left eye. She also
m acrophages. I'h is c re a te s t h e f i n e s t e l l a l e p a t t e r n o f y e l ­ 11.1: .I o- n >n‘h hi -ii "Г-, fl :i v f-rn iiIlunt lever ol unknown f■
чuir.
l o w e x u d a l e t h a t is c h a r a c t e r i s t i c o f a m a c u l a r s t a r . S t e l l a t e Her visual acuity was 20/50 in lhe left eye. Merit! swelling of
m a c u l o p a l h y is c a u s e d b y a v a r i e t y o f d i s e a s e s a f f e c t i n g l h e the lefl oplic disc (E and small white retinal lesions in Lhe lefL
p e rm e a b ility o f th e c a p illa rie s in th e d e p th o f th e o p tic 1undus Narrows, E .ind Fi and one Ihat was unnoliced in lhe
asvmplomaLic righL eye until review tri her angiographic study
n e r v e h e a d , Ite tin a J v a s c u la r d is e a s e s u s u a l l y c a u s e a m o r e
(arrows, С and Hr. The white lesions in the left eye as well as
irre g u la r and coarser d e p o s itio n o f y e llo w is h e xu d a te in
□f Lhe oplic disc sLained [h. Spinal fEuid examination revealed
th e in n e r n u c le a r as w e ll as th e o u t e r p le x ifo r m laye rs in pje*jcy1creis. SpiплI fluid and blood cultures were negaLive.
th e m a c u la r re g io n . | - L : A 2 4 - year-old female wiLh bilateral asymmetric; disc
l he d iffe r e n tia l d ia g n o s is o f p a tie n ts w i t h a n o p t ic d is c edema Secondary lo cat-scratch disease. Macular slar is seen
s w e llin g a n d a m a c u la r sLar in c lu d e s h y p e r te n s iv e r e t i n o p ­ in the more involved righL eye (J). The lefl fundus shows sev­
a t h y [se e F i g u r e s 6 . 2 5 Л a n d 6 . 2 & D ) , d i a b e t i c o p Lie n e u r o ­
eral focal inner retinitis that is often seen in thoht! patients i-L.
arrows!'. Her visual acuity was light perception in LKe right and
p a t h y a n d d ise a se s a s s o c ia te d w i l h o p t ic n e u ritis , s u c h as
2 0 / 2 0 in the lefl. There was a functional element to Lhe visual
s a rc o id o s is , b a c te ria l s e p tic o p tic n e u ritis . Lym e d is e a s e .,
Loss in the right eye. One month later her vision had improved
and lu e tic o p tic n e u ritis . A m a c u la r sta r i n f r e q u e n t l y Lo 2 0 / Ja in lhe ri^ht anti 2 0 / 1 5 in Lhe left eye and the macular
a c c o m p a n ie s d iffu s e u n ila te ra l su b a c u te n e u ro re tin itis star had broken up wilh resolution of disc swelling hilaLeraIly.
and is r a r e l y , i f e v e r , s e e n in p a tie n ts w i t h o p tic n e u ritis M: rhe paLhngenes-is of a maculaT star. Lip id-rich exudate
secondary lo d e m y e lin a lin g d i s e a s e s .2113 T h e p o s s ib ility Eeaking from capillaries within the depLh of Lhe oplic nerve
o f s e p tic r e t i n i t i s c a u s e d b y p y o g e n i c b a c te r ia ., c a t-s c r a tc h
head -[small arrows) extends inlo the subretina I space sur­
rounding the optic nerve head as wetl as along lhe outer
d i s e a s e , t o x o p l a s m o s i s , o r f u n g i is g r e a t e r i n t h o s e p a t i e n t s
plexiform layer inlo the macular re^iun. ReahsorpLion of Lhe
w h o m a n lie s t m u lt if o c a l re tin itis . T h e d iffe r e n tia l d ia g n o ­
serous portion of Lhe exudate leaves a concenlraLed lipid
sis in t h o s e p r e s e n t in g w i t h a b r a n c h r e t i n a l a r te r y o r v e i n esudale large arrows^ in lhe outer plexiform layer of Henle
i n c l u s i o n e x p a n d s Lo i n c lu d e i d i o p a t h i c r e c u r r e n t b r a n c h anti causes n macular star Lhal is usually more- prominent in
re tin a l a rte ry d is e a s e a n d L a le s ' d ise a se [se e C h a p t e r 6). Lhe nasal halt of Lhe macula.
M anagem ent o f th e s e p a tie n ts depends upon th e o c u la r L l- ii tfM irttsy uf D r . K ilrtik L zv in
fin d in g s a n d lh e p re s e n c e o r a b s e n c e o f s ig n s a n d s y m p ­
t o m s o f s y s te m ic d ise a se . M a n y o f th e s e p a tie n ts a re a fe ­ have a p p ro p ria te e v a lu a tio n in c lu d in g b lo o d c u ltu re s lo

b rile a n d Lh e a n t e c e d e n t illn e s s has re s o lve d b y th e Lim e e x c lu d e s y s te m ic s e p tic d ise a se . S e r o lo g ic te s tin g fo r e x p o ­

o f th e ir e ye e x a m in a tio n . A g e n e ra l p h y s ic a l e x a m in a tio n - sure lo H iJrtcneU ii, s k in test fo r c a t-sc ra tc h d ise a se , and

ro u tin e b lo o d c o u n ts, and s e ro lo g y to e xc lu d e s y p h i- b io p s y o f e n la rg e d ly m p h nodes m ay be a p p ro p ria te in

Eis m a y be a ll th a t is necessary. Those w ith m u ltifo c a l t h o s e p a t i e n l s e x p o s e d l o c a t s . T h e B a r K m i ’ lhi b a c i l l u s c a n

re tin itis , and p a rtic u la rly th ose w ho are fe b rile - s h o u ld be id e n tifie d w ith Lhe W a rth in -S ta rry s la in . 'L h e visu a l
I I I I I I I
I I 1 i I 1 1
p ro g n o s is fo r p a tie n ts w ilh id io p a t h ic ste lla le n e u r o re ti­ I S. [ 2 R e c u rre n t o p tic neuropathy a s s o c ia te d w ilh

n itis a n d m u l t i f a c t I r e t i n i t i s is g o o d , a n d n o t r e a t m e n t is fa m ily history of C h a r o o t - M a r r e - T o o t b d is e a s e ,

re q u ire d . A n o c c a s io n a l p a t i e n t w i l l h a v e a re c u rre n c e in
A—I: TEni-s 4&-year-old ivoman presented with decreased
th e o p p o s i t e e ye m o n t h s o r y e a rs la te r (s e e C h a p t e r 1 0 ) . vision in the [eft eye associated with pair on eye move­
P u rv in and C h io ra n re p o rte d on seven young a d u lts ments. Shu complained of j^rbiduлI decrease in periph­
(m e a n age o f 27 years) w ho d e v e lo p e d m u Eli p i e e p i­ eral Vision in both eyes over 2 years. Her lather, paternal
sodes o f m o n o c u la r n e u ro re ltn tlis , m a c u la r sta r Form a­ aLrnt, bfo’ heT, anti brol-heT's d^ujjhler carried a diagnosis of
Charcot-Marie—Tooth disease and her sisler had "uveitis."
t io n , d e n s e a rc u a te v is u a l fie ld d e fe c ts , a n d in s o m e cases
Visual acuity was 2(УЗО in the Hghl eye and counl finders
severe p e rm an e nt v is u a l lo s s .'" ' Jto th eyes w ere e ve n tu ­
in the left eye. The right optic disc was pale and the left
a lly a ffe c te d in five p a tie n ts . L a b o r a t o r y s tu d ie s w e r e n o t
swollen wilh lipid exudates into the macula IА, И'.. Optical
re v e a lin g a n d th e d is o r d e r a p p e a re d u n r e s p o n s iv e t o sys­ coherence tomography confirmed macular Ihickenin^ wi!h
te m ic c o rtic o s te ro id s . lix c e p t fo r th e presence o f a m a c u - inlTaretinaJ lipid i[Cj_ She received oral steroids followed by
Ear s ta r, t h e i r c a s e s s e e m Lo s h a r e m o r e i n com m on w ith L'yclophosph amide. The vision in Ihe 3eft eye imprm'ed lo
A 10 N in young p a tie n ts [se e d is c u s s io n o f id io p a th ic 2().''30 in 1 weeks bul Lhe right eye vision dropped lo 2(>/40o.
She now had a swollen righL optic disc and Ihe lelt macu­
A IO N in t h e y o u n g b e l o w ) .
lar exudates wyre clearing :LJ, E). four monlhs later visual
acuity had improved lo 20/50 in lhe liftht eye and JO/frO­
RECURRENT OPTIC NEUROPATHY in Ihe left eye (f, G). The optic nerves were pale wilh no
ASSOCIATED WITH FAMILY swelling and the lipid exudates were resolving. Two months
Eater all lipid exudates were absorbed with residual optic
HISTORY OF CH ARCOT-MARIE- atrophy and vision of 20/50 in Lhe ri^hl and ICWttO- in lhe
Icl L eye -H.. I . Coldmann visual fields showed severe con­
TOOTH DISEASE__________________ viction in ijoLh eyes and etectrorFtinpgiaiTi showed normal
rod nnd cone function. Neurological exam did not reveal
P ro g re s s is t m u s c u la r w e a kn e s s and a tr o p h y th at b e g in in
neuropaLhy (]r myopalhy. She wan negative for the known
th e firs t t w o d e c a d e s o f life c h a r a c te r iz e G M T d ise a se s p e c -
mutations for Leber's heredilary optic neuropal hv. A biqpsy
L r u m . C M Г is a g e n e t i c a l l y h e t e r o g e n e o u s g r o u p o f d i s e a s e s
of her normal skin was consistent With aUtoimmune/con­
th at a c c o u n ts fo r a lm o s t 9 0 % o f h e re d ita ry p o ly n e u r o p a - nedive tissue disease, She has been continued on low-dose
t h i e s . - 10L|_S(M l h e c o m m o n e s t f o r m , C M T t y p e 1 , is a n a u t o ­ immunosuppressi ves.
s o m a l - d o m i n a n t ly in h e rite d d e m ye ! m a tin g n e u ro p a th y
m a p p e d m o s t c o m m o n l y to th e s h o rt a rm o f c h r o m o s o m e
1 7 ( 1 7 p l t .2 '| typ e IA. and a fe w to lo n g a m i o f ch rom o­ e x u d a tio n th at im p ro ve d w ith s yste m ic s te ro id th erap y

som e I (typ e I B ) . t y p e 2 G M T h a s a s im ila r c lin ic a l p h e n o ­ each lim e (fig u re l!> . 12 ) .

t y p e b u t n e r v e c o n d u c t i o n is n o r m a l , s u g g e s t i n g t h e d i s e a s e
ёб n e u r o n a l ra th e r th a n d e m y e l i n a t i n g , tt is i n h e r i t e d i n a
FAMILIAL DYSAUTONOMIA
d o m in a n t fa s h io n (s h o rt a rm o f c h ro m o s o m e I ) o r reces-
s iv d y (lo n g arm o f ch rom osom e S ). T yp e 3 is t h e m ost ]: a m i h a l d y s a u to n o m ia (P iie y -D a y syn d rom e) is an
severe f o r m - A l> lin k e d to c h r o m o s o m e 1, th e s a m e lo c u s a u to s o m a l-re c e s s ive d is o rd e r c a u s in g c o n g e n ita l sensory
as t y p e 1 B.. a n d A l? l o c h r o m o s o m e 1 7 , s a m e as t y p e IA . and a u to n o m ic d y s fu n c tio n th at a ffe c ts A s h f c e n a j.i Jew s
X - l i r i k e d d o m i n a n t a n d re c e s s iv e f o r m s a r e a ls o s e e n . e x c lu s iv e ly .
S y s t e m ic fe a tu re s b e g in w i t h fo o t d e f o r m it i e s , p e s c a v u s , The d i s e a s e is p r e s e n L f r o m b i r t h , m a n i f e s t e d as h y p o ­
and s c o lio sis, fo llo w e d by p ro g re s s iv e w e a k e n in g o f th e to n ia a n d fe e d in g d iffic u ltie s re s u ltin g in fr e q u e n t a s p ira ­
m u s c l e s o f t h e l e g f e e l a n d h a n d s . S e n s o r }1 a b n o r m a l i t i e s tio n s a n d p n e u m o n ia s . A u t o n o m i c d is tu rb a n c e s w ith lac k
are fe w . [’ r e g r e s s iv e o p lic a tro p h y th at u s u a lly b e g in s in o f e m o tio n a l tears, d e fe c tive body te m p e ra tu re c o n tro l,
th e s ix th d e c a d e o r la te r h a s b e e n r e p o r t e d in s e ve ra l p e d i- c o ld hands and fe e l, e xc e s s ive s w e a tin g over head and
g r e e s . - 5 0 7-- ^ S u b c lin ic a l o p tic n e u r o p a t h y c a n b e d e te c te d tru n k when e m o tio n a lly e xc ite d , s k in b lo tc h in g b lo o d
by e le c tro p h y s io lo g ic te s tin g in a s y m p to m a tic in d iv id u ­ pressure la b ility , and o rth o s ta tic h y p o te n s io n are h a ll­
a ls . C M T t y p e 6 is e s p e c i a l l y a s s o c i a t e d w i t h o p t i c a t r o p h y . m arks o f th e d is e a s e . Ihere is a l s o decreased s e n s itivity
Jh is 4 0 -y e a r-o td w o m a n h a d a fa m ily h is to ry o f c lin ic a lly lo p a in a n d te m p e r a tu r e , h y p o - от a re fle xia . p o o r c o rn e a l
d ia g n o s e d C M T d is e a s e in her b ro th e r, n ie c e , p a te rn a l s e n s a t i o n , a n d p u p i l l a r y a b n o r m a l i t i e s .!l1 P r o g r e s s i v e o p t i c
a u n t , a n d fa th e r. S h e h a d n o n e u r o E o g jc a ! dise a se , b u t p r e ­ a L r o p h y is s e e n i n t h o s e p a t i e n t s t h a t s u r v i v e b e y o n d e a r l y
se n ted w ith re c u rre n t o p t ic n e u ritis a s s o c ia te d w ith lip id c h i l d h o o d . 4 -'' "1
NEURORETJNOPATHY 1 E 3 A c u t e n e u r o r e l i n o p a t h y a n d p r o g r e s s iv e fa c ia l
h e m ia tro p h y (P a rry -R o m b e rg s y n d ro m e ),
AND PROGRESSIVE FACIAL
A—C : This 21-year-old wornдгк vl+io had developed a linear
HEMIATROPHY depression a$ Iha forehead and scalp tiEginrlifin al 4 yuars of
ajje (A) Ii.i 11a Ь-week history af acaLe visual loss in- Ihi? ipsi-
P ro g re s sive fa c ial h e m ia tro p h y (P a rry ^ R o m b e ig syn­
I.ileral eye caused by sleil.tle exudative neuioTotinop.il Eiy Li:.
drom e) is a d i s o r d e r o f u n k n o w n c a u s e l h a l is c h a r a c t e r ­ Нет visual acuily was 5 / 2 0 0 . Optic Cora mi na roenlg^ogtaflss
i s e d jj$f p r o g r e s s i v e u n i l a t e r a l a t r o p h y o f l h e s k i n , m u s c l e s , weTe normal Three and one-half years laLer, the oplit disc
and bony s tru c tu res o f th e fa c e r u s u a l l y in p re a d o le s c e n t was pale (C) and hw visual acuity was 20/00.
p a t i e n t s . 3 1' ^ ! Jls-333 il m ay e xle n d d o iv n in to lh e neck- D -G : This 6-vear-old Еюу developed progressive loss of
vision i n the left eye on the same si do that he- had facial
s h o u ld e rs , iru n k , a n d e fc lre m itie s. A l! o f lh e fa c ial s tr u c ­
hemiatrophy (Di lhal began at t уеяК uf aye. H i s visual acu­
t u r e s o n o n e s i d e m a y b e i n v o l v e d (E -'igure- 3 5 . 1 3 t D a n d J I ) ,
ity was 10/400. He had a stellate exudative neurorelinopathy
o r th e re m a y be o n l y л lin e a r d e p re s s io n in t h e sc a lp a n d iL . A nj^ic►j’rapEi у fevealed capillary dilation (Fj) and Iale sLai idl­
fo re h e a d [c o u p d e sabre) (F ig u re 15.1 З А ). V itilig o , p o lio ­ ing in the атеа (if lhe sWpllen optic disc. It also showefd evi­
sis.. n e v u s f l a m m e t i s , a n d m o le s are o fle n present o n th e dence of some dilation and leakage of the peripheral rhinal
a ffe c te d s id e . P to s is , tric h ia s is , ta g o p h lh a h n o s * e c lro p io n , capillaries (C)L Com puled lomo^raphy i'CTi revealed normal
n e u r o p a r a ly t ic k e r a titis , c a n a l i c u l a r o b & l r u c l i o n , dacryocysr-
oplic canals. Echography and CT showed some evidence of
dislenlron of the left opLic nerve shea Ih.
Litis, e xlra o c u la r m u s c le p a lsie s , e n o p h th a lm o s , Н о гп е гЧ
H and I: This 13-year-old hoy wilh progressive facial hemiat­
s y n d r o m e , h e t e r o c h r o m i a o f t h e tris.. u v e i l i s , o p t i c a t r o p h y
rophy :Hl, lefl deatness, ccmgeniL.il howrLl defetl, and bypc-
a n d p ig m e n ta r y d is tu rb a n c e s o f th e fu n d i m a y o ccu r, lh e spadias developed loss of vision in Lhe right evu because of
b ra in m ay show e vid e n c e o f h e m ia t r o p h y ,, b o m o la te ra ! peripheral relina] telangiectasis and exudative retinal detach­
m ig ra in e , c o n tra la te ra l e p ile p s y, e vid e n c e o f e n c e p h a li­ ment ill. A sin'.ilar exudalive detachmenl was presenl in liis
tis.., i n t r a c r a n i a l v a s c u la r m a lfo r m a t io n s ; and o c c a s io n a lly opposile eye. Cryolherapy Wnis successful in reaLlachin^ lhe
m o v e m e n t d i s o r d e r s m a y b e p r e s e n t .'1 T h is s y n d ro m e Ivlina in both eyes.
is n o l u s u a l l y a s s o c i a t e d w i l h v i s u a l l o s s . V i s u a l l o s s , h o w ­ ll'E .in r f I f r t im C i i c t . 1'-’ i

e ve r, m a y b e c a u s e d b y e ith e r ip s ila le ra l n e u r o r e t i n o p a l h y
c h a r a c t e r i z e d b y a c u te v i s u a l lo s s , o p l i c d is c s w e l l i n g , p e r i ­
p a p i l l a r y e x u d a t i o n . , a n d m a c u l a r s L a r. o r r e t i n a l t e l a n g i e c ­
tasis a n d e xu d a tiv e re tin a l d e ta c h m e n l {fig u re 15 .1> A-1
and see lig u re & 4 0 t - L ] b3 1 5 - 3t s U ltra s o n o g ra p h y
m a y d e m o n s t r a t e s o m e e n l a r g e m e n t o f l h e a fT e c le d o p t i c
nerve. T h e o p tic fo ra m in a are norm al ra d io g ra p h ic a lly.
O p t i c a l r o p h y m a y o c c u r as t h e p e r i p a p i l l a r y a n d m a c u l a r
e x u d a tio n c le a rs , but no p a tie n t has d e m o n s tra te d pro­
g re s s iv e lo s s o f v i s u a l fie ld . P e l i n a l v a s c u la r a b n o r m a l i l i e s
h a v e b e e n r e p o r t e d p r e v i o u s l y i n th is d i s o r d e r ' " [se e
in fa rc tio n o f th e a n te rio r part o f lh e o p lic nerve caused
C h a p te r 6, C o a ts' s y n d ro m e ).
by re d u c tio n in b lo o d lo w to lh e nerve [Fig u re s 1 5.1 4
'lh e p a th o g e n e s is o f lb e a c u le n e u r o r e lin o p a t h y a n d re ti­
and 1 5 . ! 5 ). T h e o p t i c n e r v e h e a d , b y v i r t u e o f ils c l o s e l y
n a l v a s c u l o p a l h y is u n k n o w n ' l h e p a t h o g e n e s i s o f t h e e n t i r e
arranged nerve fib e rs w i l h i n th e n o n e x p a n s i le i n l r a s c l e r a l
d i s o r d e r is c o m p l e x a n d p o o r l y u n d e r s t o o d . A u t o n o m i c d y s ­
c a n a l, is id e a lly s itu a te d fo r is c h e m ia to occu r. P rim a ry
f u n c t i o n s e c o n d a r y t o s y m p a t h e t i c a b n o r m a l i t y as e v i d e n c e d
v a s c u la r in s u ffic ie n c y or secondary v a s c u la r in s u ffic ie n c y
by H o r n e r 's s y n d r o m e ' " r3S1; a u to im m u n e e tio lo g y due lo
caused b y a n y p r o c e s s l h a l p r o m o t e s sta sis o f a x o p l a s m i c
p o s i t i v e a u t o a n t i b o d ie s t o d o u b l e - s t r a n d e d D N A , and som e
f lo w a n d n e rv e fib e r s w e llin g c a n ca u se is c h e m ia . A L O . N t y p ­
fe a tu re s c o m m o n t o s c l e r o d e m n a ' ' ' '" ; f a c i a l t r a u m a as d i e
ic a lly a ffe c ts o l d e r p a tie n ts , a n d (h e a c u le 1<jss o f vis io n tn a y
i n c i t i n g f a c t o r t r i g e m i n a l n e u r it is as e v i d e n c e d b y h e m i f a c i a l
be m is ta k e n ly a ttrib u te d to a m a c u la r d is o r d e r fo r e x a m p le ,
c h a nge s; g e n e tic e tio lo g y d u e to fa m ilia l o c c u rre n c e ; d e v e lo p ­
m a c u la r d e g e n e ra tio Li i f p ig m e n l e p ith e lia l c h a n g e s are p re s­
m e n ta l a b n o n n a l i l y ; p o ssib le e n c e p h a litis d u e to a sso c ia tio n
e n t,- o r l o c y s lo id m a c u la r e d e m a tn th e a p h a k ic p a tie n t
o f R a s m u s s e n e n c e p h a l i t i s i n s o m e ^ :' h a v e al l b e e n c o n s i d ­
(F ig u re 1 5 . 1 4 k a n d L ] . F o r p a lh o g e n e lic as w e ll as th e ra p e u ­
e r e d . N o n e o f Lh ese h y p o t h e s e s e x p l a i n s a ll t h e m a n i f e s t a t i o n s
tic r e a s o n s , t h e s e p a t i e n l s c a n b e s u b d i v i d e d i n l o t w o m a j o r
s e e n i n t h e c o n d i t i o n . \i is b e s t c o n s i d e r e d a d i s o r d e r o f c l i n i c a l
su bgrou ps: [lj a n o n a rte rilic g r o u p , n - A I O N (tb o .s e w ith ­
h e te ro g e n e ity lik e ly c a u s e d b y e tio lo g ic a l h e te ro g e n e ity .
o u t e v id e n c e o f a rte rilis r У 5 % ) and ( 2} a n a rte ritic g r o u p .
a - A I O N (L h o s e w i t h g ia n t-c e ll a rte ritis , 5 ^ о ). l h e n o n a rte ritic
ANTERIOR ISCHEMIC OPTIC g rou p m a y b e s u b d iv id e d in lo an id io p a th ic g ro u p , th o s e

N EUROPATHY_____________________ w i l h n o id e n tifia b le ca u s e, a n d th o s e w ilh a p r o b a b le cause,

h in c tio n a lly , o p h lh a lm o s c o p ic a lly , a n d flu o re s c e in a n g io -
]" h e te rm "a n te rio r is c h e m ic o p tic n e u ro p a th y" is used g r a p h i c a l l y , a ll s u b g r o u p s m a y p r e s e n t s i m i l a r f i n d i n g s , l h e
to d e s c rib e s w e llin g , is c h e m ia , and. v a ry in g degrees of v i s u a l p r o g n o s i s , h o w e v e r r is n o l t h e s a m e f o r a ll g r o u p s .
Idiopathic ("Nonarteritic") Anterior E5 . 14 N o n a rte r itic a n le rto r isch e m ic n e n ro p a th y .

Ischemic Optic Neuropathy A - С : This 5 7 - y e a r - o l d Wcimarl w it h r t d r t L h y r o i d

e K o p E u h a lm o s n o t e d ra p id Eoss o f vision in the lefl e y e . H e r
Over 50% o f p a Lie n ls w i t h tt:A I O N are g e n e r a lly h e a l t h y visual .у : u :v v. ■i'. I J 1.:: ■. I К ell jptit dis< w a i s w o l le n , a n d
p ^ litn ls W h o se a g e is 4 5 y e a r s o r o l d e r [m e a n o f 5 7-6 5 a fla m e -s h a p e d h e m o r r h a g e Was pre s e n t at ils m a rg in ' A .
years) and w ho e xp e rie n c e an a n ile , u s u a lly m o d e ra te A n g i o g r a p h y s h o w e d a m a r k e d incre a se in relircal c i r t u l a -
Eo s s o f v i s i o n i n o n e e y e ( 2 0 / 5 0 l o 20 / 200 ) over hours lo Lion t im e a n d late staining o f lhe disc (B a n d Q , S h e h a d an

d ^ . 33^ 4" U n l i k e p a lie n ls w ilh o p lic n e u r i t Ls o r a r t e r i t i c

inferior a ttilu d in a l vis u al fie ld d e fe c t. T h e a c u it y r e m a in e d
2 0 /2 0 0 ir> spile of intensive oral co rLico sle ro id LneaLrnent for
A lO N ( a - A l O . N ) , p a i n a n d h e a d a c h e are n o t fe a tu re s . A b o u t
2 m o n t h s , She received X - r a y irradiation to th e left o r b it . H e r
104-pi r e p o r t a i n i n o r d i s c o m f o r t . Ijess l h a t i 5 % report p r o ­
a c u ily 1 Ve UI later ■was 2(1/40.
d r o m e s u c h a s i n t e r m i t t e n t t r a n s i e n t v i s u a l b l u r s .,, s h a d o w s , 0 a n d E : A c L ile visual loss a n d an inferior alliLudinal field
o r sp o ls lhat m ore o fte n accom pany a -A lO N . O p tic d is c defect o c c u r r e d in lhe righl e y e nl" Ibis Elbalthw e ld e rly p a lie n l
s w e llin g a c c o m p a n ie d b y o n e o r several fla m e -s h a p e d h e m ­ W ith o p t i c disc s w e l lin g a n d ju x l a p a p il ta r y h e m o n h a g e s (Dp
o r r h a g e s is u s u a l l y e v i d e n t ( f i g u r e 1 5 . 1 4 ) . T h e s w e l l i n g m a y a n d a visual a c u ity d e c re a se to 2 0 / 4 0 . T h e EefL e y e was n o r ­

o r m a y n o t b e p a l l i d . El m a y b e m o r e p r o n o u n c e d in th e mal w it h 2 0 / 2 0 visio n -El.

s u p e r io r h a l f o f th e o p lic d isc . A lo w e r a llitu d in a l o r a rcu ­
a t e f i e l d d e f e c t t h a l o f t e n is m a x i m u m a l l h e t i m e o f p r e s e n ­
t a t i o n b u t t h a l m a y p r o g r e s s d u r i n g t h e first f e w w e e k s o f
t h e d i s e a s e is p r e s e n t .4 UA O c c a s io n a lly h a rd e xu d a te s a n d
c o t t o n - w o o l s p o ls are p re s e n t (7°/n). F lu o r e s c e in a n g io g r a ­
p h y u s u a lly d e m o n s tra te s a d e la y o f p e r fu s io n o f th e o p tic
f- : Th is 6 7 - y e a r - o l d patient w it h m a r k e d inferior LiEting o f
b o th o p t i c discs d e v e l o p e d a cute visual Eoss a n d a n in fe ­
rior a llitu din a l field defect in lhe rigEn e y e . N o l e Lhe p a le
s w e llin g o l the u p p e r part o f Ihte d isc (Ft a n d the [u x L a p a p il-
lary Htibnetmal hem o rrhinge . S e v e ra l m o n L h s laler Lhe b l o o d
reso lved a n d I here w a s гетп лткпЫу lillle pa ILot o f th e o p t i c
disc i C t .

d i s c b l o o d v e sse ls, m i n i m a l a l t e r a t i o n s o f c h o r o i d a l f i l l i n g ,
G —|: T h is 6 T - y e a r - o l d hy p e rte n s iv e w o m a n e x p e r ie n c e d
visual loss lo 2 0 /4 0 0 d u e lo a n o n a rte filic a n te rio r is c h e m ic
a n d s t a i n i n g o f t h e o p t i c d i s c [E 'ig u r e ] 5 . 1 4 1 i a n d C ) . '"iJ I n
o ptic n e u r o p a t h y 2 y e a rs p r e v io u s ly in the rigbL e y e w h i c h
s o m e c a s e s t h e r e is a d e l a y i n t h e r e l i n a l a r t e r y a p p e a r a n c e
e v e n t u a lly i m p r o v e d to 2С УВ 0 . S h e d e v e l o p e d is c h e m ic o p l ic
tim e , a n d a n in c re a s e d re tin a l c ir c u la tio n tim e , t h a l p r e s u m ­ n e u r o p a t h y associated w iLb a Ej ranch retinal ar^Sry ot e lu s io n
a b l y Is c a u s e d b y c o m p r e s s i o n o f t h e c e n t r a l r e t i n a l v e s s e l s in lh e left eye., a n d he r v is io n d r o p p e d to fl/20 0 . She а1мэ
by L i :.: H '.v n lle n is d n -in lc iu t .'c i i l u ' r . i:i I :i l - r e g i o n -4 Lie h a d line t u L i c u la r d ruse n in b o th eyes lhat lit up e a rly o n lhe
l a m i n a c r lb r o s a . T h is c o m p r e s s i o n o c c a s i o n a l l y m a y b e s u f­ a n g io g r a m ( H a n d IE- T h e vessels o n the disc w e r e d ila t e d
fic ie n t to cause a f u n d u s p ic tu r e o f c e n lra t re tin a l a rle iy o r find lh e I'low thTou g h lhe Ljrbinn:h retinal a rtery w a s d e la y e d .
Н е т vis ual a c u ily in the left e y e i m p r o v e d Lo 2 0 / 5 0 - in 2
ve in o c c lu s io n (h ig u re 15 .14Л -С }. O c c a s io n a lly th e c o m ­
m o n t h s , l h e iira n c b relinal arLery s h o w e d s h e a lh in g a л d Lbe
p re s s io n c o u ld o c c lu d e a c ilio re lin a l a rtery or a bran ch
disc e d e m a h a d resolve d ij.i.
re tin a l a rte ry c o m i n g o f f th e d is c ( F ig u r e 15 .140 -1). Focal К a n d L: T h is 6 7 - y e a r - o l d h y p e r te n s iv e p a li e n l e x p e r ie n c e d
L e la n g ie c ta tic c h a n g e s m a y a p p e a r o n th e s u rfa c e ve sse ls o f visual Eoss c a u s e d b y iscEiemic o p t i c n e u nopal Eiy (K) s o o n
th e d is c w i l h in a fe w d a ys , c o n s id e r e d to be l u x u r y p e rfu ­ after u n e v e n tfu l calaract e x tra c tio n . C y s t o id m a c u la r e d e m a
s io n d u e to a u lo r e g u la t o r y re s p o n s e b y in c re a s e d p e r fu s io n was su sp e cte d , b u t a n g io g ra p E iy re v e a le d staining o f Lbe
s u r r o u n d i n g a n in fa rc t. S o m e t i m e s this m a y b e In te r p re te d
o ptic disc a n d n o e v id e n c e o f retinal c a p illa ry le a k a g e in Lbe
m a c u la . H e s u b s e q u e n t ly d e v e l o p e d o p t i c a t r o p h y ( L j. A s im ­
as a c a p illa ry h e m a n g io m a or n e o v a s c u la riiia tio n when
ilar c o u r s e o f e v e n ts o c c u r r e d in Elis leFl e y e .
p ro m in e n t [Fig u re ! 5 . 1 4 K ) . V:U lhe d is c s w e llin g re so lve s
K.'-l, cftJHt'sycJ Dr. L lIw . l h I Ctjfitttty.l
in several w e e k s , l h e d is c b e c o m e s p a le a n d u s u a lly s h o w s
m i n im a l c u p p in g . S p o n ta n e o u s im p r o v e m e n t o f visu a l acu ­
ity o c c u rs i n 1 0 - 3 5 % o f c a s e s .3 il-3S5 E i e c u m e n c e o f n - A E O N
in th e sam e eye is i n f r e q u e n t . 11J 5J ETo s s i b l e e x p l a n a ­
tio n s Г о г th e i n fr e q u e n t re c u rre n c e s in n - A I O N i n c l u d e lo ss a tta c k s o f A l O N in Lh e s a m e e y e ,'- u a n d th e s m a l i c u p / d is c
o f n e r v e fib e rs a fte r n - A I O N . p r o v i d i n g m o r e space f o r s u r­ l a t i o 1^ 134' 359'3^ ' 360'364- 36* s u g g e s i l h a t s t r u c t u r a l f i d o r a a r e
v i v i n g n e rve fib e rs t o sw e ll, a n d s h u n t i n g o f b l o o d fr o m th e i m p o r t a n t in th e p a th o g e n e s is o f i d i o p a t h i c A l O N ,
a r e a o f i n f a r c t i o n t o t h e s u r v i v i n g p a r t o f t h e n e r v £ L u ' <' ?^ "]' A s s o c ia te d d is o rd e rs th a l m ay p re c ip ita te n o n a rte ritic
A p p ro x im a te ly ^0 % o f p a tie n ts w ill d e v e lo p n -A IO N in A lO N In c lu d e d ia b e te s , m a lig n a n t h y p e rte n s io n [E 'lg u r e
th e o p p o s ite e y e ." " A lth o u g h it h a s been presum ed th at 1 5 . 1 5 A a n d f i ) , u r e m l a , - ll!7,16 f e c l a m p s i a , ^ ' J- 1 -J m i g r a i n e , - ^ "
m ost of th es e p a tie n ts p ro b a b ly have an a rte rio s c le ro tic n n tip h s ^ , 371-373 h e m o d y n a m ic shqpk 3?-^75 a n e m i a , 376
d is o rd e r, th e re is m i n i m a l e vid e n c e lo s u p p o r t ih is v ie w . p a p ille d e m a , o rb ita l in fla m m a tio n (Fig u re 1 5 .1 4 A -C ) ,
These p a tie n ts have no g re a te r In c id e n c e o f c a rd io v a s c u ­ c a la ra c l e x tra c tio n ( H g u r e 1 5 .13К a n d 377-380 e l e v a t i o n
la r or c e re b ro v a s c u ta r d ise a se th a n a m a tc h e d grou p of o f i n t r a o c u l a r p r e s s u r e , , 6 ": c o n g e n i t a l a n o m a l i e s o f t h e
pa fltte iiis .346'3^ 5*2 I d i o p a t h i c o r n - A I O N occurs a l a y o u n g e r o p liic d i s c , a n d o p t i c d is c d r u s e n . :t!i b u b r e t i n a l n e o v a s c u ­
a g e i n s m o k e r s ( m e a n a g e 53 y e a r s ) c o m p a r e d t o n o n s m o k ­ l a r iicat i o n o c c a s io n a lly o c c u r s .ш F a m ilia l n -A LO N has
e r s ( m e a n a g e (>4 y e a r s }.-11-0 T h e f r e q u e n c y o f i n v o l v e m e n t i n be e i^ r e p o r L e d .^ '' ! L O \ - A 2 9 m a y be a risk fa c lo r f o r d e v e l­
th e u p p e r h a l f o f Lhe o p lic d is c , U fi th e ra rity o f s e c o n d o p m e n t o f n - A I O N . ЗЯЙ
. 'i и frrri ir i-ri Uctmc O p t ic rupalh\f I28 7
 I Listo p a t h o l o g i c e v i d e n c e s u g g e s ts L h a l v a s c u l a r i n s u f f i ­ \Ъ.\Ъ A n te r io r is c h e m ic o p t ic n e u r o p a th y (A lO N ).
c ie n c y c a u s in g a c u te is c h e m ic s w e llin g o f a s e g m e n t o f th e
A a n d K: П е т и rrha g i t nonarLerilic A l O N ass<*ciaLod w i l h
nerve fib e rs i m m e d i a t e l y p o s t e r i o r t o th e l a m i n a c r ib r o s a a b ra n c h reLinal a rtery o c c lu s io n in a se ve re ly h y p e rte n s iv e
is re s p o n s ib le fo r th e c lin ic a l p ic tu re of n -A IO N .^ 4 0 -y e a r-ol cl p a IienL. h o l e ischem ic w tiitu n in g o f the retina
V a s c u lo p a th y o f th e p a r a o p lic b ra n c h e s o f th e s h o rt p o s ­ ьu регсЛеф рога 11u (fi).
te rio r c ilia ry a rte rie s m ay p la y a m a jo r ro le . Jh e reason (. : A rte rilic A l O N in а frft-yea r-o ld m n i s n w it h cranial arte+
fo r th e s u s c e p tib ility o f th e s u p e r io r s e g m e n ts o f th e o p tic ritis. S h e p re s e n te d b e c a u s e o f b lu rr e d v is io n in the left e y e .
S h e p re v io u s ly losl vision in 1he fight e y e . N o l o lh e m a r k e d
n e r v e to is c h e m ic d a m a g e a n d th e ro le o f n o c t u r n a l h y p o ­
pa II о i the swt) len oplic ■:!;s-. Sc-, civ. m o n t h s I. i ' i t lhe
t e n s i o n a n d s l e e p a p n e a are u n c e r t a i n .
□p-lit: d isc was alrrjph-ic.
A d d i t i o n ; ) I fa cto rs th a t m ig h t a ffe c t p e r fu s io n such as
D a n d £: N o n a r le r E tic is c h e m ic o p lic n e u r o p a t h y ca u s e d b y
o p tic d is c d r u s e n , h y p e r o p ia , e le v a te d in tr a o c u la r p re ss u re, a cu le b l o o d loss o c c u r r e d m Ihis 4 7 - y e a r - o l d w o m a n w h o
m ig r a in e , a n d d r u g s s u c h as s ild e n a fil a n d in te r f e r o n -a lp b a e K p o rfe n c e d mashive e\Lraw isaLion o f b l o o d in to Lhe b o d y 1 is­
m ay have a ro le in som e cases. A m i o d a r o n e m ay its e lf sues associated w i lh lip o s u c Lio n . O n the first p o M o f ie j,i I ive
c a u s e to x ic o p tic n e u r o p a t h y o r trig g e r a n is c h e m ic o p tic
d a y s h e n o le d r o a r in g in Ihe ear a n d n o lighL [je r c e p lio n in
the right e y e . T h e right o p L ic d is c w a s s w o l le n a n d p a le (-D).
n e u ro p a th y in s u s c e p tib le in d iv id u a ls , h e n c e a h is to ry o f
The? left e v e w a s n o rm a l :l-l. H e r h e m c ^ l o b f n was .‘j .li, a n d
its u s e s h o u l d be s o u g h t." ^ I h e r e is n o p roven tre at­
h e m a to c riL w a s 1 6 . .Magneflic re s o n a n c e irnagjn# o f th e b ra in
m e n t fo r n - A l O N ; a s p i r i n is r e c o m m e n d e d f o r its r o l e in was n o r m a l . S h e w a s treated w i t h p r e d n is o n e , f l O m j j daily,
d e c re a s in g stro k e s a n d m y o c a r d i a l in fa r c t io n s in t h is va s- a n d re c e iv e d 2 units o f b l o o d . H e r v is io n i m p r o v e d Lo light
c u lo p a th ic p o p u la t io n .iM p e rc e p tio n o n ly .
F -L : T h is 3 0 -y e a r -o ld w o m a n n o tic e d d o u b l e v is io n for 2
d ays p r io r (o presen Lai io n . T h e d o u b l e v is io n w a s re p la c e d
Idiopathic Anterior Ischemic Optic b y a superior field loss o n the d a y o f p re s e n Lai ion in h e r right
Neuropathy in the Young (AIONY) e ye . Н е т Vfciial a c u ity w a s 2G/.40 in this e y e a n d 20/20- jn the
unalYecLed left e ye . T h e in fe r io r h a lf o l th e o p t it: d isc s h o w s
Id io p a th ic A l O N Y is a r a r e e n t i t y c h a r a c t e r i z e d by recu r­
рл 11 id s w e l lin g (F ). A flu ores cein a n g io g r a m shenvs d e la y e d
re n t e p is o d e s o f a c u te v is u a l lo ss a s s o c ia te d w i t h s e g m e n ­ c h o r o id a l fillJnj; al s e c o n d s ■:С.] I a n d u p Lo 7 7 s e c o n d s
tal p a l l i d s w e l l i n g o f t h e o p t i c n e r v e t h a t f r e q u e n t l y c a u s e s I l-П. S h e w a s b e in g LrcaLed fo r lelL t e m p o r o m a n d i b u l a r j(]inl
severe and p erm a n ent v is u a l lo ss in o th e rw is e h e a lth y arlhrilis for -1-5 m o n t h s . S h e d e n ie d scalp tenderness a n d
y o u n g a d u lts w it h a mean age o f o n s e t o f 25 y e a rs . ' 11 ш w e ig h t loss, b u t w a s m i l d l y irritable. 5 h e re c e iv e d 1 g r a m

]Ъ е fu n d u s p ic tu re a ltd visual fie ld changes d u rin g th e Gff in l ia v e n o u s s o lu m e d r u l Jollcjw ed b y o ra l p r e d n is o n e . A

lempctra! a rte ry b io p s y s h n w e d Ih ic k e n e d arterial w a ll w i ll:
a c u te s ta g e a re id e n tic a l l o th o s e in n - A l O N . I h i s s im ila r ­
infiltra tion o f in f l a m m a t o r y a n d giant cells (a rro w , fl a n d a n
it y i n c lu d e s t h e s m a l l o p t i c d is c s iz e . M e d i c a l e v a l u a t i o n is
e x tre m e ly n a r r o w e d l u m e n :l a n d J, a r r o w heads:-, hler visjem
n e g a t i v e . T h e c a u s e is u n k n o w n . r e m a in e d at 20 /3 0 w it h a s u p e r io r fie ld d e fe ct. T h e o p l i c disc
I t is i m p o r t a n t t h e r a p e u t i c a l l y to d i ff e r e n t i a t e n - A l O N s h o w s p a llo r in Ihe infe rio r half a L 1 m o n l h IK, L (arrow )).
and A I D N Y fro m a -A I O N . lh e b lo o d s e d im e n ta tio n ra te , II .itk J I, r:uur!Ljiy Ml LJr. {jy tc kihrnun.i
a c u te -p h a se re a c la n Ls such as C - re a c tiv e p ro te in s , and
p la te le t c o u n t s a re u s u a l l y w i t h i n n o r m a l lim it s in n - A l O N
ArteritSc Anterior ischemic Optic
and A i O N V a n d are u s u a lly g re a tly e le v a te d in m o s t cases
o f a -A iO N .
Neuropathy ia-AION)
' i h e r e is n o e ffe c tive tr e a tm e n t f o r n - A L O N or A IO N Y . G ia n t-c e ll arteriLis (te m p o ra l a rte ritis* c ra n ia l a rte ritis)
O p tic n e r v e s h e a t h d e c o m p r e s s i o n w a s s u g g e s t e d as e f f e c ­ is a s y s t e m i c d ise a se lh a t is c h a r a d e r ^ e d by a rth ra lg ia s,
tive in th e tre a tm e n t o f th e a c u te p ro g re s s ive stage of headaches, fe ve r, w e ig h t loss, ja w c la u d ic a tio n , m y a lg ia ,
n - A I O N / 9 L-iM Evid e n c e , how ever, in c lu d in g th e re su lts a n d , fr e q u e n tly , a c u te severe v is u a l lo ss in o n e e ye lh a t is
o f a c o n tro lle d c lin ic a l tria l, in d ic a te s Lhat th e p ro c e d u re o fte n f o l l o w e d b y se ve re lo ss in t h e s e c o n d eye in e ld e rly
is in e ffe c tive and m ay be h a rm fu l fo r th e tre a tm e n t of p a tie n ts , u s u a lly 60 years o f age o r o l d t T .< llU l^ Is c h e m ic
n -A lO N .555 1""r- 40; 'lh e rate o f o p e ra tive c o m p lic a tio n s , n e c ro sis o f t h e sc a lp m a y o c c u r in severe u s e s : o f t e n th e s e
w h ic h in c lu d e c e n tra l re tin a l a rtery o c c lu s io n a s s o c ia te d p a tie n ts a re a ls o irrita b le d u e Lo (h e m y a lg ia in t h e e x a m ­
w i l h o p t i c n e r v e s h e a t h d e c o m p r e s s i o n , m a y b e as h i g h a s in in g lh e v is u a l lo ss is g e n e r a l l y m ore pro­
40 % n 'j y n e a i m e Q t o f i h e a s s o c i a t e d s y s t e m i c d i s o r d e r s i n fo u n d L h a n in n - A E O N , a n t i t h e o p t i c d i s c p a l l o r is u s u a l l y
p a tie n ts w i t h n o n a rLe ritic A lO N , fo r e x a m p le , c o rtic o s te ­ m ore s trik in g (fig u re 15 .15 D and V and H gure 6 .2 :5 1 .].
ro id s o r X -r a y im i d i a L i o n i n o r b i t a l i n f l a m m a t o r y dise a se C o tlo n -w o o l p a tc h e s and lla m e -s h a p e d h e m orrh ag es
(E 'ig u r e 15 .I4 A -C ], b lo o d tra n s fu s io n fo r p a tie n ts with n w be pre se n t. O th e r fin d in g s m ay in c lu d e h y p o lo n y .
a n e m ia , or h e m o d ia ly s is in p a tie n ts w ith u re m ia , m ay e xtra o c u la r m u s c le pa lsies , and c e n tra l re tin a l a rte ria l
im p ro v e th e p ro g n o s is f o r r e t u r n o f v i s i o n . i b ? -36fl P a t i e n t s as w e l l as c h o r o i d a l a rte ria l o c c lu s io n (see H gure 6.23J.
w ilh e vid e n c e o f a -A L O N re q u ire p rom p t tre a tm e n t with H u o re s c e in a n g io g ra p h y d e m o n s tra te s d e la y e d p e rfu s io n
h ig h d o s e s o f c o r tic o s te r o id s (see n e x t s u b s e c t io n ) . o f th e c h o r o i d a n d o p t ic d isc [ r i g u r e IS .]50 a n d H ) . : " JL|
ih e W esLergren s e d im e n ta tio n rate is u s u a lly 100 J i n m 15. E 6 Meningiom a o f lh e o p tic disc.
or g re a te r; O r e a c tiv e p ro te in s and p la te le ts are e l e v a t e d .
A - G : Blu rre d v is io n , p a p i l l u d e m a , a n d chorionetin л I Folds
In c re a s e d p la s m j v is c o s ity decreased red cell f i L l-e r a b i l­ in I his 4 6 -y e a r-old v r a m a ti w e f s ca u s e d b y л m e n i С м о гл а
Ely. and decreased h e m a to c rit are o t h e r fin d in g s in th es e ol the lell optic: n e rv e <A). N o t e resolu-licm ol lire e d e m a s n d
p a t i e n t s .'112 ih e s e d im e n ta tio n rate and te m p o ra l a rtery folds a n d Lhe d e v e l o p m e n t o f diEaLed v e n o u s loops- (a rro w s,
b io p s y fin d in g s are im p o rla n l in d iffe re n tia tin g a -A E O N E j Lhal o c c u r r e d s p o n ta n e o u s ly o v e r a 3 2 - m o n l h p e r io d .
fro m j i - ;\ [O N .|IL,,,mJ O c c a s i o n a l l y ih e re m a y b e a d e la y in A n y i o ^ i a p h v sh<jwed e v i d e n c e LhaL v e n o u s b l o o d in Lhese
lo o p s a * w e ll as I hat in the relina w a s d r a in in g in lo the c e n ­
Lhe ris e o f t h e s e d i m e n t a t i o n ra le . lie n e e a h i g h in d e x o f
tral relinal v e i n . TEie patient b a d Э й О О К Ы X - r a y irradia­
s u s p ic io n b y p o s itive re vie w o f syste m s w a rra n ts a repeal
tion Го Ihe o ^ h t o rb it. N o L e the re d u c e d p r o m i n e n c e ot" Lhe
check 1- 2 d a y s late r. I l i o p s y o f t h e t e m p o r a l a rtery s h o w s
v e n o u s lo o p s 1 3 m o n t h s later ( C l . V is u a l a c u ity w a s 20 /20 .
in filtra tio n a n d th ic k e n in g o f th e m e d ia and p ro life ra tio n D a n d E: I b i s 1 4 - y e a r - o l d b o y d e v e l o p e d b Eu rre d v is io n
En to lh e lu m e n th u s o b lite ra tin g it, re s u ltin g in v a s c u la r 4 m o n t h s p r e v io u s ly after b e in g stTLick o n lh e t h i n w i l h a
in s u f fic ie n c y (I'ig u r e I S . 1 5 I a n d J} . S y s t e m ic c o r tic o s te r o id s b ro o m s tic k . H e w h s ] гол led tor 4 w e e k s w i l b l O O t n g p r e d ­
s h o u ld be in s titu te d p r o m p t l y i f g i a L i t - c e l l a r t e r i t i s is s u s ­
n is o n e daily. H is visual a c u ily w a s iiaru b a n d m o v e m e n t s ,
rigjiL e y e , a n d 20/20,. left e y e . H e h a d 2 m m ol" rif^bt p r o p L o -
p e c te d . M o n i t o r i n g c h a n g e s in Lh e b l o o d s e d i m e n t a t i o n rate
нis. O r b i t a l m a g n e tic re s o n a n ce im a g in g s-tiowed a m a s t Lhal
o r C - r e a c t i v e p r o t e i n is u s e d t o a d j u s t L h e c o r t i c o s t e r o i d d o s ­
faifed to e n h a n c e w iLh g a d o l i n i u m . O p t o c i l i a r y shunt vessels
age/" - w h i c h s h o u ld b e c o n t in u e d fo r 2 years o r m o r e , i h e Ia rr o w s , [J; suggested a m e n in g io m a lhal w a s c o n f i r m e d on
g o a l o f s t e r o i d t h e r a p y Es t o p r e v e n t l o s s o f v i s i o L i i n L h e f e l ­ b io p s y o J a n e n la r g e d o p l i c n e r v e . A n g i o g r a p h y {Ej s h o w s the
l o w e y e a n d i n v o l v e m e n t o f o t h e r c r a n ia l a rte rie s . v e n o u s nature o f shunL vessels. I-Ее r e c e d e d 4 .> 0 0 ( C y irradi­
D e v e l o p m e n t o r p ro g re s s io n o f v is u a l loss o c c u r s r a r e ly a tio n . The fu nd u s fchtfnges stabiliBen k>uI Ihere was no visual
in p a lie n ts w i l h g ia n l-c e ll a rte ritis a fte r lh e in it ia t io n o f g lu ­
im p r o v o m e n L .
f : M e n i n g i o m a ol lbcf o p lic n e r v e in this 5 o -y e a r-o ld w o m a n
c o c o rtic o id therapy.3 ’N Jn a re tro s p e c tive stu d y o f 245
w iLb ju x la p a p illa ry chorionctin ial folds.
p a t i e n t s W ttfa g i a n t - c e l l a r t e r i t i s s e e n o v e r a 5 - y e a r p e r i o d at
Lhe M a y o G i n k , A ie llo a n d c o w o rk e rs f o u n d th a t 14% had
p e r m a n e n t lo ss o f v is io n in o n e o r b o l h e y e s .'"'1 I n a l l b u t p u n c t u r e a re o f l i m i t e d v a lu e in d e f i n i n g a c a u s e fo r v is u a l
t w o o f lh e p a tie n ts , v is u a l loss o c c u r r e d b e f o r e i n s t i t u t i o n o f
lo ss o th e r th a n o p lic n e u ritis a sso c ia te d w ith d e m y e lin ­
c o r t i c o s t e r o i d t h e r a p y . V i s u a l lo ss p r o g r e s s e d a fte r c o r t i c o s t e ­ a t i n g d i s e a s e ,416 T h e М Й 1 is m o r e lik e ly lo be p o s itive in
r o id th e r a p y in th re e p a tie n ts . A f t e r 5 ye ars th e p r o b a b i l i t y
p a ti e n ls w i l h s e v e re v i s u a l lo ss. L h e p r e s e n c e o f o l i g o c l o n a l
o f d e v e l o p i n g v is u a l loss a fte r i n i t i a t i o n o f o r a l g l u c o c o r t i ­ b a n d s in th e c e r e b r o s p in a l flu id c o rre la te s w E lh th e d e v e l­
c o id tre a tm e n t w a s d e te rm in e d to b e 1% ( K a p l a n - M e ie r),
opm ent o f c lin ic a lly d e fin ite m u ltip le s c le ro sis . P a tie n ts
a n d t h e p r o b a b i l i t y o f a d d i t i o n a l Loss i n p a l i e n t s w h o h a d a w ilh r e t r o b u lb a r n e u ritis are m o r e Lik e ly l o s h o w e v id e n c e
v i s u a l d e f i c i t al t h e t i m e t h e r a p y w a s b e g u n w a s ] 3 % .
o f m u ltip le s c le ro sis th a n th ose w ith p a p il Li i ts . Eillc itin g
O th e r rare c a u se s of a -A [O N are p e r i a r t e r it i s nodosa, e ith e r U h l b o f f s s y m p L o m [Lra n s ie n l b lu rrin g o f v is io n d u r ­
C h u ig -S tra u s s s y n d r o m e , W e g e n e r s g ra n u lo m a to s is , sys­
i n g e xe rc is e , h o t s h o w e r o r b a t h , o r w h i l e u n d e r e m o t i o n a l
te m ic lu p u s e ryth e m ato su s, rh e u m a to id a rth ritis , and s t r e s s ) o r L h e r m i t l e rs s i g n ( s u d d e n o r t r a n s i e n t e l e c t r i c - l i k e
re la p s in g p o ly c h o n d r itis . T h e s e c o n d itio n s s h o u ld be c o n ­
s h o c k s r a d ia lin g d o w n th e s p in e o r e xtre m itie s , p a rtic u la rly
s id e re d in p a tie n ts w h o p r e s e n l e a rlie r th a n 6 0 ye a rs o f ag e w i t h L i e c k f l e x i o n ] Es e v i d e n c e i n p a t i e n t s w i t h u n e x p l a i n e d
o r i f r e v ie w o f s ys te m s p o in is to a n y o f t h e m .
visu a l lo ss, su g g e s tin g re tro b u lb a r n e u ritis anti m u llip le
s c l e r o s i s . I f c l i n i c a l s i g n s a c i d s y m p t o m s a r e l y p l c a t f o r o p Lie
ID IO P A T H IC O P T IC N E U R IT IS A N D n e u ritis, o lh e r w o r k - u p is u n l i k e l y l o b e f r u i t f u l . I f L h e f e a ­

P A P IL L IT IS _____________________________ t u r e s a r e a t y p i c a l , s u c h as p r o g r e s s i o n o f v E s u a l Lo s s b e y o n d
1 w e e k , e v i d e n c e o f vitritEs. p r e s e n c e o f a m a c u l a r s t a r fig u re
lh e re s u lts o f lh e O p l i c N e u ritis T re a tm e n t T ria l, w h ic h o r iritis, a g e m o r e t h a n 4 3 y e a rs , o r a b s e n c e o f p a in , o t h e r
e n ro lle d 4 4 8 p a lie n ts . in d ic a te thal t h i s d i s o r d e r es c h a r ­ d ia g n o se s, such as s y p h ilis , c a t-s c ra lc h dise a se , sy sle m ic
a c te rize d b y a c u le v is u a l lo ss, o f t e n a sso c ia te d w ith p a in lu p u s e r y t h e m a t o s u s , l .y m e dise a se , vira l o r b a c te ria ) o p t ic
(5 0 % ) w orsened by eye m o ve m e n t, in p re d o m in a n tly n e u ritis s h o u ld be c o n s id e re d . In m o s t p a tie n ts th e visu a l
fe m a le s ( 7 7 % ) w i l h a m e a n a g e o f 3 2 years ( 2 0 - 5 0 y e a rs ), a c u ity a n d v i s u a l die l d r e t u r n t o norm al w ith En a y e a r .M '
'ih e o p lic d i s c is s w o l l e n in a p p ro x im a te ly o n e -th ird of In Lhose p a tie n ts who at th e onset o f v is u a l s y m p t o m s
cases. M a c u l a r s la r fig u re s o c c u r r a r e l y . ' i h e p a tie n ts d e m ­ h a v e M l i l e v i d e n c e o f m u l t i p l e s c le ro s is -1 Eke l e s i o n s , i n t r a ­
o n s t r a t e a w i d e v a r ie ty o f visu a E fie ld d e fe c ts. C o l o r v i s i o n v e n o u s th e r a p y w E lh c o rtic o s te ro id s re d u ce s th e c h a n c e s o f
Es a L m o s t a l w a y s a b n o r m a l a t i d a r e l a t i v e a f f e r e n t p u p i l l a r y lh e p a ti e n t's d e v e l o p i n g n e w c lin ic a l sEgns o f m u l t i p l e scle ­
d e fe c t is s e e n . M R 1 o f t h e b r a i n s h o w e d e v i d e n c e o f d e m y - r o s i s d u r i n g t h e s u b s e q u e n t 2 y e a r s . "■S- I|IJ l h i s re s lra En in g
e lin iza tio n in a p p r o x im a t e ly 5 0 % o f cases. М Ш , s e r o lo g ic effe ct o f c o r t i s o n e w e a rb o f f a fte r 2 ye ars. O r a l a d m i n i s t r a ­
s tu d ie s (a n tin u c le a r a n tib o d y , flu o re s c e n t tre p o n e m a l t i o n o f c o rtic o s te ro id s h as n o e ffe c t o n v is u a l o u t c o m e a n d
a n tib o d y -a b s o r b e d ], chest X -r a y e x a m in a tio n , a n d lu m b a r i n c r e a s e s t h e r i s k o f r e c u r r e n t o p l E c n e u r i t i s .11
O P T IC N E U R IT IS IN C H IL D R E N E5.E6 C o n tin u e d

G : P h o t o m i c r o g r a p h ol m e n i n g i o m a o l the o p t i t n e r v e . M o l e
O p l i c n e u r i t i s i n c h i l d r e n is u n i q u e i n t h a t it i s m o r e o f t e n c o m p r e s s io n o f the o p t i t nerve (a rrow s) Езу Lhe tum o r.
a n te rio r b ila te ra l, k n o w n to o ccu r ] - 2 w e e k s a fte r a p re ­ H a n d I: M e n i n g i o m a o f lh-о o p ! i t n e r v e w it h ап I prior e x t e n ­
sum ed v i гл! in fe c t io n , le ss o fte n a s s o c ia te d w ith d e ve l­ sion inlo the sulbtetinal s p a ce Ia n o w , J.. S o r e t h i 1 evijtfertce o f
opm ent o f m u ltip le s c le ro sis a n ti is s t e r o i d - s e n s i t i v e or c h o ro id a l folds Narrows, ll fldjijcenl Lo l h e s u b ie lin a l t u m o r .
sle ro id -d e p e n d e n t. '['h is s h o u ld be d iffe re n tia te d fro n ] O p t i c n e rv e g lio m a
n e u r o r e t i n i l l s s e c o n d a r y t a c a t - s c r a t c h d i s e a s e L h a t is m o r e
3— Thi s 1 ti-y e a r-o ld C a и casinin W o m a n oresenled w i l h p r o ­
o f t e n u n i l a t e r a l a n d is c h a r a c t e r i z e d b y d i s c s № l | n g p e ri­ ptosis, lim ile d e v e m o v e m e n l s , o p t i c atropEiy U l> a n d n o
p a p illa ry e xu d a tiv e d e ta c h m e n t, and m a c u la r sta r fo r­ light p en coplion v is io n . 1 1 - w e i^ h le d as ini I m a g n e tic reso­
m a tio n . T h o s e w ho p ro g re s s lo d e v e l o p m e n t o f m u l t ip l e n a n c e ttniailng w!:lii g a d o lin i u m s h o w e d an irregular f liyilc-srin
s c l e r o s i s nire o l d e r a n d h a v e u n i l a t e r a l i n v o l v e m e n t ^1 ^44 e r l l a rg^ifnent o f Lhe rij^hl o p t i c nerve [|}H ihal w a s s e c tio n e d
f K 1. H i s t o l o g y s b o w u d K o s o n th a ] i'iEiefs l y p i t a l ot" ] u v e n fle
p i l o t y l i c a s tro c y to m a \ L i.
T R A U M A T IC O P T IC N E U R O P A T H Y I l' l fr u r n D u n n .ir u l W . i Ib-h-1"1'. А I A n u 'M L im M l i i I m ol A s b O L h L lJu n . A l l
1-3.. LiiurtLTf [Jr. M .Ejnq IMi-iMj.'i
B lu n t in ju rie s , p a rtic u la rly to th e fo re h e a d , m ay cause
Loss o f v i s i o n and no f u n d o s c o p i c c h a n g e s as a r e s u l t o f is o p le rs . E u K ta p a p illa ry re tin a l a n d c h o r io r e tin a l fo ld s m a y
i n j u r y l o t h e o p t i c n e rve , e v e n w h e n th e t r a u m a s e e m s triv-
be present [Fig u re 15 |б Л , G, and E). Ex te n s io n o f th e
b a l .101 1 ■ -jh e o p tic n e rve is m o s t v u l n e r a b l e Lo i n j u r y
t u m o r i n t o t h e i n n e r e y e is r a r e (3: i g u r e 1 5 . I G l - L ).414-44 In
at e it h e r e n d o f t h e o p t ic c a n a l S h e a r i n g fo rc e s c a u s e d b y
th e p re s e n c e o f o p t ic d is c e d e m a , flu o re s c e in a n g io g r a p h y
a b ru p t d e c e le ra tio n o f th e s k u ll p ro b a b ly cause in ju r y lo s h o w s c a p illa ry d ila t io n a n d Le akag e o f t h e o p tic d isc v e s ­
s m a l l n u l r i e n t b l o o d ve sse ls as w e l l a s c o n t u s i o n n e c r o s is l o
sels. L a t e r a f t e r o p t i c a t r o p h y h a s o c c u r r e d , d i l a t i o n o f t h e
[ h e n e r v e . I m m e d i a t e to ss o f v i s i o n t o n o lig h t p e r c e p tio n c a p illa rie s a n d Le a k a g e are u s u a lly n o l o n g e r a p p a r e n t , l h e
on im p a c t p o rte n d s a p o o r p ro g n o s is fo r recovery; a short
p a l Le m o f d y e fillin g th e d ila te d v e n o u s lo o p s o n th e o p tic
Eu cid in te rva l b e fo re d e te rio ra tio n su g ge sts a p o te n tia lly d is c s u g g e s t s , a t le a s t in s o m e c a s e s , t h a t t h e s e v e s s e ls m a y
re ve rs ib le process. D ire c t in ju ry lo lh e nerve m ay re s u lt
n o t b e s h u n t in g v e n o u s b l o o d f r o m th e re tin a i n t o th e ju x-
f r o m a fra ctu re t h r o u g h th e b o n y c a n a l th a t severs o r c o m ­ la p a p illa ry venous syste m but in s te a d are h y p e r t r o p h i e d
p r e s s e s t h e n e r v e . rL h e v a l u e o f c o r t i c o s t e r o i d s a n d s u r g i c a l
c o lla te ra l c h a n n e ls tra n s p o rtin g venous b lo o d fro m th e
d e c o m p r e s s i o n i n b o t h t y p e s o f i n j u r y is u n c e r t a i n .4j7 O p t i c re tro b u lb a r m e n in g io m a into th e c e n tra l re L i n a ! v e i n . ’ -1"'
d isc p a l l o r u s u a lly a p p e a rs s e v e ra l w e e k s a fle r l h e in ju r y .
H is to p a th o lo g ic e xa m in a tio n in one case d e m o n s tra te d
c o m m u n ic a tio n b e tw e e n th e re tin a l v e in s and th e cho­

R A D IA T IO N - IN D U C E D O P T IC ro id a l v e i n s . 4 '"- P rim a ry o p tic nerve m e n in g io m a s occa­

s i o n a l l y o c c u r b i l a t e r a l l y , i ' " - 1 ^ . 4,1? a n d m a y b e a s s o c ia te d
N EU RO PA TH Y
w ilh n e u ro fib ro m a to s is typ e 2 a lo n g w ith c ra n ia l nerve

See C h a p t e r 6. s c h w a n n o m a s . 4 '11' M e n i n g i o m a s as w e l l a s a c o u s t i c n e u r o ­
m a s m a y b e c a u s e d b y loss o f t u m o r s u p p r e s s o r g e n e s o n

O P T IC N ER V E M E N IN G IO M A S ch rom osom e 22 . 4 4 'J

С Г and u l t r a s o n o g r a p h y are i n v a l u a b l e in d e m o n s t r a t ­
P a tie n ts w ith m e n in g io m a s c o n fin e d lo lh e o rb ita l por­ in g th e e n la r g e m e n t o f th e p e rio p tic d u ra ! sh e a th s a n d in
tio n o f th e o p tic nerve чi r e ty p ic a lly w om en [70 -8 0 % ) e xc lu d in g tumor e xte n s io n in to th e o p tic c a n a ls . A b o u t
w h o are se e n b e tw e e n th e a g es o f 3 5 a n d 6 0 y e a rs b e c a u s e o n e -th ird o f p a tie n ts s h o w c a lc ific a tio n on С Г scan th a l
o f tra n s ie n t o h s c u ra Lio n s o f v is io n o r m ild v is u a l lo ss in a p p e a r s as b r i g h t l i n e s a l o n g t h e l e n g t h o f t h e n e r v e ; t h i s
one eye [ E - 'i g u r e 1 5 . 16 A -E lh e v is u a l a c u ity is is c a l l e d t h e " t r a m t r a c k " s i g n . M R l p l u s f a t s a t u r a t i o n a f t e r
u s u a lly norm a! or o n ly m ild ly a ffe c te d . W ild p r o p to s is g a d o l i n i u t n - d i e t h y l e n e p e n t a a c e t i c a c i d is h e l p f u l I n d e t e c t ­
is p r e s e n t in 5 0 -75 % o f cases a n d is e a s i l y o v e r l o o k e d . in g in tra c ra n ia l e x te n s io n o f o p tic n e rv e m e n i n g i o m a th a l
O p h th a lm o s c o p ic e xa m in a tio n ly p ic a lly re ve a ls m ild is n o l e a s i l y i m a g e d w i t h M H I a l o n e . 4 j J ‘l3ft ] Ъ е d i f f e r e n t i a l
o p tic d is c e d e m a and som e d ila tio n o f Lh e re tin a l v e in s d ia g n o s is in c lu d e s o p tic n e rv e g lio m a , p a p ille d e m a , and
[E 'ig u r e 15 .16A). O th e r e vid e n c e o f c e n tra l re tin a l v e in o p tic nerve cysts. In som e cases a n o c c u lt m e n in g io m a
o b s t r u c t i o n is i n f r e q u e n t l y p r e s e n t . i * ' L n l a i g e m e n t o f t h e m a y b e th e cause o f th e c y s t i5Q W h e r e a s o p tic d is c p a l ­
b lin d s p o t is t h e c h a r a c te r is tic fie ld d e fe c t in itia lly . Over lo r a n d c o lla te ra l v e n o u s c h a n n e l s Hire h i g h l y s u g g e s tive
a p e rio d o f m o n th s o r ye ars v is u a l lo s s , in c r e a s e d p a p i E l - o f a m e n in g io m a , th e y o c c a s io n a lly are c a u s e d b y o th e r
edem a (H g u re 15 J61) and f), re fra c tile b o d ie s a n d p n il- d is o rd e rs such as c e n tra l re tin a l v e in o c c lu s io n , hyd ro­
lo r o f th e o p tic d is c , m ild re tin a l w i n d ila tio n , and in c e p h a l u s , a n d p e r i o p t i c n e u r i t i s .'1 1 А -'2 V i s u a l l o s s t y p i c a E l y
2 0 -4 0 % of cases optic d is c shunl or c o lla te ra l ve sse ls occu rs s lo w ly o v e r a p e r io d o f m o n t h s o r years, a n d su r­
d e v e lo p (fig u re 15.L6EJ a n d o ) . A- ' A ' ' - * A '' T h e s e c h a n g e s g ic a l e x t i r p a t i o n o f th e m e n i n g i o m a is u s u a l l y a s s o c i a t e d
are u s u a l l y a c c o m p a n i e d b y c o n t r a c t i o n o f t h e p e r i p h e r a l w i t h p r o f o u n d v is u a l lo ss. I h e r e f o r e , in p a t ie n t s w i t h g o o d
v is u a l fu n c tio n a n d no e v id e n c e o f e X tra o rb iia ] e x te n s io n 15-1 C h o r o id a l fo ld s a s s o c ia te d w ilh u n ila te ra l d is c
o f th e m e n in g io m a , o b s e rv a tio n fo r e v id e n c e o f p ro g re s ­ e d e m a o f u n k n o w n c a u se ,
s iv e v i s u a l lo s s o r e x t r a o r b i t a l e x t e n s i o n is u s u a l l y r e c o m ­
A a n d B : Ttiis a p p a r e n tly hen Ithy 3 5 -y e a r -o ld m a n p re s e n ted
m ended b e fo r e e i t h e r s u rg ic a l o r i r r a d i a t i o n tre a t m e n l is w it h visual c o n ip la in l s in the left e y e . H is right e y e w a s п о г ­
c o n s i d e r e d . 4■
10'4 Ч -‘|3<мЛ^ 5 i A ^ Som e p a tie n ts a c h ie v e at нил!. in the I ell e y e b e h a d p a p ille d e m a a n d h o r i z o n t a l l y
Least to tn p o ra ty re s to ra tio n o f v is io n fo llo w in g irra d ia ­ o rie n te d c h o rio re tin a l folds (arroW s, A l . H e n o le d further
t i o n t r e a t m e n t . ’ "' " 1 ' ' O p t i c n e r v e m e n i n g i o m a s i n c h i l d r e n d e c lin e in fils a c u it y a n d re turned 3 d a y s later. H is visu al
a cu ity w a s 2 0 / 6 0 . T h e p a p ille d e m a h a d lessened. Ttie c h o ­
and yo u n g a d u l t s are m o r e a g g re ssive a n d th es e p a tie n ts
riorelinal folds w e r e u n c h a n g e d . I H ; N e u r o l o g i c e v a l u a t i o n
re q u ire c lo s e r t b U a W - u p .',3 S i M ^
in c l u d i n g c o m p u l e d lo m o g r a p h v s c a n w a s n e g a tiv e .
( : t h is J 4 - y e a r - o ld w o m a n h a d hilaleral s w o lle n npCic discs
s e c o n d a r y [o p s e u d o L u m o r c e re b ri. S u b re tina l h e m o r r h a g e
w a s seen at I h e e d g e o l ib e s w o l le n disc f t r a r r o w J.

OPTIC NERVE GLIOMAS Sub retinal neovascularization associated wilh

papilledema secondary to idiopathic intracranial
O p t i c n e rv e g l i o m a s c a u s e in s i d i o u s lo ss o f v i s i o n , p r o p l o - hyperlension.
sis.. a n d o p tic a tr o p h y [ f i g u r e I 5 . L 6 J in s e t) t h a t are o f t e n
D - H : Ibis 3 0 -y e a r -o ld w o m a n h a d p a p ille d e m a fro m id io ­
d is c o v e re d in c h ild re n d u r in g a ro u tin e eye e x a m in a tio n . p a th ic in tracra n ia l h y p e r te n s io n ( □ a n d Ef. T h e r e w a s a p ig ­
Jh e y represent o f a ll c r a n i a l t u m o r s a n d 1.5- 3 .5 % o f m e n t e d I v p e 2 j t f t t a p a p j lla r y i K N V . V i in the lefL evE-4 at Ihe
o rb ita l lu m o rs . T h e tu m o r m a y in v o lv e o n e o r b o th o p lic s u p e m t e m p o r a I e d g e o f th e disc. T h irte e n m o n t h s later she
n e r v e s a l o n e ( 2 5 % I o r m a y i n v o l v e t h e c h i a s m a n d tract in d e v e l o p e d a s e c o n d S K N V M al the in te ro Le m p o ra l d isc e d g e
w it h l a a k a g e o f flu id , b l o o d ; a n d I if] id . A n g i o g r a m nb o w i; an
a d d itio n to th e o p tic n e rve ( 7 5 % ) . W h e n b o th n e r v e s are
active S R S V . M al the in fe r o t e m jio r L l e d g e o t Ihe disc a n d a
a f f e c t e d t h e p a t i e n t is l i k e l y L o h a v e o t h e r m a n i f e s t a t i o n s
s p o n ta n e o u s ly in v o lu t e d 5 K N V M at I h e s u p e r o te m p o ra l e d g e
o f t y p e Э n e u r o f i b r o m a L o s i s , f o r e x a m p l e , Ljeisch iris n o d ­ ot the disc ia r r o w .. i h e u n d e r w e n l k r y p t o n red laser p h o l o -
u le s a n d b r ig h t le s io n s d e m o n s t r a t e d t h r o u g h o u t th e h r a in c o a g u la t io n ol lh e .active m e m b r a n e w it h g ra d u a l re s o lu tio n
w ith g a d o lin iu m -e n h a n c e d M C t i .4 'l" h e la tte r le s io n s o f Ihe i b i d , b k u x J , a n d h p id o v e r 3 m o n t h s . Six years laler
h a v e u n c e r t a i n p a t h o l o g y a n d c o n s e q u e n c e s . ' 1Ъ е у p r e s e n t Hie lei vr.- (.-I:■■i;^. V ■- iг -г I'. '.-i I th a Mii.i Ii■:-i ■! i .м. I ho
w i t h in s id io u s lo ss o f v i s i o n a n d p r o p lo s is . H y p e r o p i a a n d s u p e r o le m p o r a l m e m b r a n e w a s n e v e r treated.

c h o r io r e lin a l fo ld s m a y be seen in a n te r io r l u m o r s d u e lo N u tritio n a l a m b ly o p ia .

c o m p r e s s io n o f lh e p o s te r o r w a ll o f d ie e ye . P o s te r io r o p lic j and |: N u lr i ti o n a l a m b ly o p i a m is d ia g n o s e d as m a c u la r
n e rve g lio m a s p re s e n t as a s lo w ly p ro g re s s ive o p lic n e u ­ d e g e n e ia lio n in Ihis tifj-year-oJd m a n , w h o c o m p la in e d o f lo s s
r o p a th y . K a d io lo g ic s tu d ie s m a y reveal e n la r g e m e n t o f th e erf central vision o f iwcr l b m o n lh s ' dur.i1 ion. H is visual a c u -
o p L ic f o r a m e n o n t h e a ffe c le d s id e o r e v id e n c e o f J -s h a p e d ily w a s 20/ 100 . There w e re m ild r e l i n a l fiij'm e n t e p ith e liu m
cha ng e s b io m E c fo s c o p ic a lly 11 a n d |). A n g io g r a p h y , h o w e v e r,
s e l l a t u r c i c a i n t h e c a s e o f c h i a s m a ! i n v o l v e m e n t , '['h e o p l i c
was n o r m a l. H e h a d bilateral ceoocenlral s co Lo m a la . l-te wi]s
nerve e n la rg e m e n t is f u s i f o r m in shape and shows m ild
Lnealed w it h oral a n d intram uscular injections o f K - c o m p l e x
e n h a n c e m e n t o n g a d o lin iu m sc a n n in g (fig u re 15.16J and V i t a m i n s a n d w it h in several m o n t h s e x p e rie n c e d d r a m a l i t
K). O p tic nerve g lio m a s have a va ria b le h is to p a th o lo g ic im p r o v e m e n t o f vision й ы В О / З ц a n d j - l + in b o th e y e s .
appearance a n d g ro w th p o te n tia l. M o s t n eu ra l tu m o rs o f К a n d L: This 73-y e a r-o ld m a n , w it h a h is lo iy o t rionLrop ica I
th e a n te r io r v is u a l p a tlm a y s g e n e ra lly b e n ig n a n d are s p ru e a n d life lo n g a m b l y o p i a in lhe left e y e , n o le d the deveE-
c la s s ifie d as p i l o c y l i e a s t r o c y t o m a s . S o m e , how ever m ay o p m e n l o f a p a race n tral s c o t o m a in lhe right e y e 6 m o n t h s
p r e v io u s ly . H e w a s e a lin g a w h e a t-fr e e d iet. V is u a l acuiLy i r
e x h i b i t a g g r e s s i v e g r d W t h a n d r a r e l y m a y i n v a d e t h e e y e . " :l
Lhe rfghL e y e w a s 2 0 / 4 0 a n d in Lhe left e y e 2 0 / 4 0 0 . H e h a d
T h o s e w ith le s s g r o w t h p o t e n t i a l f r e q u e n t l y o c c u r i n a s s o ­
a c e c o c e n lra l s c o t o m a in lh e righl e v e . H is pupLls a n d right
c i a t i o n w i t h o t h e r m a n i f e s l a l i o n s o f n e u r o f i b r o m a t o s i s . " ’ 0-'
fu n d u s w e r e n o r m a l e \ c e p l for a s m a l l, о л е - c lo t JK - h o u r sec­
I h e m a n a g e m e n t o f th e s e t u m o r s is c o n t r o v e r s i a l . ^ 4*3 tor o f p a llo r l e m p o r a lly in the o p t i c disc larro w , K j. T h e left
o p lic disc w a s h y p o p la s tic ( L i . T h e d iagno sis w a s p o s s ib le
n u lr h io n a l a m b l y o p i a or fo c a l ischem ic optic a l m p h y .
[C, ■>:.iiiii Ur. P.LiriL к L.T. in,'
VISUAL LOSS SECONDARY h em orrhage (I'ig u r e J5 .I7C ), a n d s u b re Lin a l n e o v a s c u la r­
i z a t i o n (I'ig u r e 1 5 . 1 7 D - G J .
TO PAPILLEDEMA CAUSED BY T h e p r i m a r y g o a l o f t r e a t m e n t is l o p r e s e r v e v i s i o n and
INCREASED INTRACRANIAL a lle v ia te s e c o n d a r y s y m p t o m s . T r e a t m e n t c o n s is ts o f o ra l

PRESSURE d iu re tic s , w e ig h t loss, lu m b a r p u n c tu re , and o c c a s io n a l

use of c o r tic o s te r o id s .’ " ш C o rre c tio n of th e second­
A lth o u g h tra n s ie n t o b s c u ra tio n o f v is io n es a fre q u e n t a ry causes su c h as im p r o v in g o xy e n a tio n and d e c re a s in g
c o m p la liit of p a tie n ts w ith p a p ille d e m a and in c re a s e d h y p e rc a p n ia , tre a tm e n t o f h y p e r th y ro id is m , a n d n e p h ro tic
in tra c ra n ia l pressure, m ost o f th e m have norm al vis u a l syn d rom e is n e c e s s a r y w h e n a p p r o p r ia t e . In p a tie n ts w i t h
a c u ity d u r in g t h e e a r ly stages. Headache, nausea, v o m it­ v i s u a l Loss w h o fa il t o r e s p o n d l o m e d ic a l th e ra p y , o p tic
in g , p h o to p h o b ia , and d ip lo p ia due to abducens nerve n e rv e s h e a th d e c o m p r e s s io n is a n e ffe c tiv e f o r m o f Ire a l-
p a ls y are n o n vis u a l m a n ife s ta tio n s . Jh o se w ith c h ro n ic m e n L il7BvJ* ‘l " q0Ll It p r o b a b l y s h o u ld be done in itia lly in
p a p i l l e d e m a , p a r t i c u l a r l y p a tie n ts w i t h p s e u d o t u m o r cere­ o n ly one eye sin c e in som e p a tie n ls th is will re s u lt in
b r i , m a y d e v e l o p l o s s o f v i s u a l f i e l d a n d v i s u a l a c u i t y i n as re s o lu tio n o f p a p ille d e m a b i l a l e r a H y ' 11"’ ' R e c u r r e n c e s m ay
m a n y as 3 0 4 4 о Г cases. K e r v e fib e r laye r a tr o p h y w i t h o c c u r . I:"" ] " h o s e w i t h h e a d a c h e a s t h e i r p r e d o m i n a n t s y m p ­
s l i t - l i k e о т d i f f u s e l o s s is b e s t v i e x v e d b y u s i n g t h e r e d - f r e e to m m ay undergo v e n lric u lo p e rilo n e a l or lu m b o p e rilo -
E i g h t a i t h e s l i t l a m p . P e r s o n s a t h tg .li r i s k o f v i s u a l l o s s a r e neal sh u n t.
th o s e w it h h ig h -g ra d e o r a tr o p h ic p a p ille d e m a , peri p a p il­
l a r y s u b r e t i n a l h e m o r r h a g e .'1'1 a n e m ia , h ig h m y o p ia , a n d
o ld a g e . "f"' I h e p r i m a r y c a u s e o f v i s u a l l o s s is p r o g r e s s i v e
NUTRITIONAL AMBLYOPIA
a t r o p h y a n d d e g e n e r a t i o n o f t h e n e r v e f i b e r s . +"'' O l h e r le s s (TOXIC/NUTRITIONAL OPTIC
fre q u e n t causes in c lu d e ju x ta p a p iEla ry s u b re tin a l neovas­
NEUROPATHY)____________________
c u la riza tio n /" A p re re tin a l h e m o rrh a ge that o ccu rs
when th e rise i n in tr a c r a n ia l p r e s s u r e is r a p i d ,'172- *7S c e n ­ In s id io u s and s lo w ly p ro g re s s iv e lo ss of c e n lra l vis io n
tral re tin a l v e in o c c l u s i o n / '" serous m a c u la r d e ta c h ­ a s s o c ia le d w i l h c e n tra l a n d c e c o c e n tra l v is u a l fie ld d e fe c ts
m e n t/' m a c u la r s t a i;4 7 i,il' m a c u la r p ig m e n ta t io n ," m a y b e c a u s e d b y d ie ta ry d e fic ie n c y o f o n e o r several v it a ­
A I O N .J 6 and c h o rio re tin a l fo ld s (fig u re I5 .17A and m i n s as w e l l a s b y e x p o s u r e l o t o x in s o r a d v e r s e re a c tio c i
q The ta tte r th re e fin d in g s are not usu­ lo p h a r m a c e u t i c a l s .1''1 In itia lly th e v is u a l lo ss is nol
a l l y a s s o c ia te d w i t h v is u a l lo ss w h e n th e y o c c u r in p a tie n ts u s u a lly a s s o c ia le d w i t h f u n d u s c h a n g e s ( f i g u r e 1 5 . 1 7.1 a n d
w ilh p a p ille d e m a . O c c a s io n a lly th e p a tie n t m a y b e a w a re ]). liva n e s c e u l d ila tio n and to r tu o s ity o f s m a ll re tin a l v e s ­
o f a t e m p o r a l s c o t o m a a s s o c ia le d w i l h e n la rg e m e n t o f th e s e ls w i t h i n l h e a r c u a t e a r e a s o f t h e n e r v e f i b e r l a y e r s i m i l a r
b lin d s p o t .'14 i n s u c h cases, p a rtic u la rly i f th e o p t ic d is c l o t h a t d e s c r ib e d in Ш О К , h o w e v e r, h a v e b e e n d e s c rib e d
s w e l l i n g is u n i l a t e r a l , v i s u a l f i e l d t e s t i n g m a y y i e l d a b l i n d d u r in g th e e a rly p h a s e o f a c u te m a h iu lr itio n o p tic n e u r o p ­
s p o t e n l a r g e m e n t fa r larg er t h a n c a n b e e x p l a i n e d o n th e a t h y . ' 10 '' J e m p o r a l d i s c p a l l o r a n t i a t r o p h y o f t h e p a p i I l o ­
b a sis o f th e p a p ille d e m a . (See d is c u s s io n o f id io p a th ic rn a c u la r n e r v e fib e r la y e r e v e n t u a l l y o c c u r ( I ’ ig u r e 1 5 . 1 7 K ) .
b l i n d s p o t e n la rg e m e n t s y n d ro m e a n d acute z o n a l o c c u lt D e m o n s tra tio n o f a c e c o c e n lra l s c o to m a , p a rtic u la rly to
o u te r r e t in o p a t h y in C h a p t e r 13.) red te st o b je c ts , w i t h p re s e rva tio n o f p e rip h e ra l fie ld s is
th e ty p ic a l fin d in g . D e fic ie n c y o f lh e Б -c o m p le x v it a m in s
(p re d o m in a n tly th ia m in ) is p ro b a b ly m ore im p o rta n t
PSEUDOTUMOR CEREBRI ih a n e ith e r c h ro n ic use o f a lc o h o l or to b a c c o a lo n e in
(IDIOPATHIC INTRACRANIAL c a u s in g v is u a l lo s s , l h e re a r e o n l y a f e w w e 11- d o c u m e n t e d
HYPERTENSION) cases o f l o x i c a m b l y o p i a in sm okers w ilh no h is to ry of
a tc o h o E in g e s tio n or n u tritio n a l d e fic ie n c y ^ A re lia b le
Id io p a th ic in tra c ra n ia l h y p e rte n s io n occurs p rim a rily in d i e t a r y 7 h i s t o r y is o f t e n b e s t o b t a i n e d f r o m a f r i e n d o r r e l a ­
y o u n g obese w oEnen and le s s o f t e n in m e n , w ith o u t e v i­ tiv e o f th e p a lie n l. M o s t o f th es e p a tie n ts s h o w im p ro v e ­
dence o f u n d e rly in g d ise a se . In about Ю ТЪ o f p a tie n ts m e n t o f v i s i o n f o l l o w i n g i n s t it u t i o n o f a b a la n c e d d ie t acid
s e c o n d a ry causes in c lu d e e x o g e n o u s su b sta n c es o r o th e r H - c o j n p l e x v i t a m i n s u p p l e m e n t a t i o n ( f i g u r e 1 !> . ] 7 ] a n i l J ) .
s y s te m ic illn e s s e s , ie lr a c y c lin e s . n a lid ix ic a c id , w i t h d r a w a l A re v ie w o f p u b lis h e d cases o f a m b l y o p ia a m o n g m a l ­
o f b e ta -h u m an c h o rio n ic g o n a d o tro p h in and c o rtic o s te ­ n o u ris h e d a llie d p ris o n e rs o f th e la p a n e s e d u r in g W o rld
ro id s , c y c lo s p o rin e . g ro w th horm one, le u p ro lid e a c e ta te , W a r El a n d a m o n g C u b a n s s h o w e d p r e m o n i t o r y k e r a t o p a ­
lith iu m , ic ve n o rg e s ln e l l i n p la in s , vitamin Л, and o th e r th y. ra p id o n s e t o f v is u a l lo ss, a h ig h in c id e n c e o f h e a r in g
re tin o id s are known to be a s s o c ia le d . S ys te m ic d is e a s e s lo s s , a n d th e p re s e n c e o f p e r ip a p illa r y - r e l i n o p a t h y in s o m e
in c lu d e o b e s ity, h y p e rth y ro id is m , a n e m ia , o b s tru c tive cases. N o s in g le c a u s a tive fa c to r w a s id e n tifie d . C e n e tie
s le e p a p n e a , c h r o n ic re s p ira to ry in s u ffic ie n c y , p ic k w ic k ia n s u s c e p t i b i l i t y r a r e l y , i f e v e r , p l a y e d a no le a n d v i t a m i n d e f i ­
s yn d ro Ln e , an d n e p h ro tic s y n d ro m e . c ie n c y w a s n o t im p o r t a n t . P rote a n d e fic ie n c y, a n t i o * i d a n l
In a d d itio n t o t h e d isc e d e m a , s o m e o f th es e p a tie n ts d e fic ie n c y, p h y s ic a l la b o r , a n d to b a c c o s m o k i n g lik e ly c o n ­
d e v e lo p c h o ro id a l fo ld s (F ig u r e 15 .I7A and E ) , su b re tin a l t r i b u t e d t o t h e o c c u r r e n c e o f a m b l y o p i a . ' 1" '
 A p e c u lia r o p l i c n e u r a p a f h y , re fe rre d l o as W fest I n d i a n D IA B E T IC P A P IL L O P A T H Y
Ja m a ic a n o p l i c n e u r o p a t h y , is c h a r a c t e r i z e d b y lh e ra p id
d e v e lo p m e n t of v is u a l loss and o p tic a tro p h y in pre­ S e e C h a p te r fr.
d o m in a n tly young W est In d ia n b l a c k s . 4" '' ' lh e m ile -
to -fe m a le ra tio is 2 : 1 ,491 A s im ila r o p tic n e u r o p a th y has References
b e e n d e s c r i b e d i n W e s t A f r i c a n s . V i s i o n is u m i a l l y r e d u c e d 1. AtilailCaketastilA UkkNT el i.WtBousnndirah е ж cfDptiifleweptti^ serais
t o 2 0 / 2 0 0 le v e ls . A n d d e n s e c e n tr a l s c o t o m a a n d t e m p o r a l ш Ja r ачгsr. for J 1ЭЭС;' 16:j H '.
2. AleHiider ТА. 31sen Fn Vbжйг/ end tfclacsajcSlitf r itit itif r. cl ktcu;
d is c p a l lo r are c h a ra c te ris tic . Nerve d e a f n e s s r a ta x ia ., a n d itadimsrt aswc al# wlh optic та pits AM J ^ lld a rt 19S+;121!KH2
s p a s tic ity m ay accom pany ocular in vo lv e m e n t in a fe w 3. (utfylefW. HraMi G EtoirtJ.el al. Т-тыт етг cl relnaJ detacfinrniMEjiflsntalcpft: iLty
-грЮп Ьйег p talx ig j al nn. Grcelas Udi Q r E>f Oinla o l 1S)S/:22E:2'' -4
i n s t a n c e s ; t h e p a t h o l o g y is a c h r o n i c m e n i n g o m y e l i t i s w i t h
4. Зотд! M. Setcus iraciitir oUKhiHil aiicaa:ec nrti ccLl tstnS pit. c/aele:An± Ctn
lo ss о Г m y e l i n o f th e n e rv e r o o t s r i n c lu d i n g t h e o p t ic a n d ^ Ih im d is e i 2Й:52Ё-^
E. Згсап ЭС. btdd!; JA, Змиега *i. Canjeala- pra 0i t i optic петя head. II. Cnsil slaves r
a u d ito ry 7nerves w h e n i n v o l v e d . J 'L i t is u n c e r t a i n w h e t h e r
Turaii. CptiltBliTKkm l9fllE7.6'-6!i.
th is a m b ly o p ia has an in fe c tio u s r to xic , h e re d ita ry ; or 6. Зголп SC. S ia c i №.\ c?; EF. el 1 Cmgen :ai pit ci tie »Lc y.rn h&ac.. n erjjl
stutte in ceI(b dcQ& Anti О р М тц 137a:£ г:' 3 ^ 1 4
n u tritio n a l b a sis. A s tu d y of 21 in p a lie n ts in London
7. Cafioj'. FF. Sianal afcbtma 1 Ts i t : печч aisrasnK fltti hces h t-s Ы . aid a [}Sl ct
re ve a le d d e m y e lin a lio n as a p o s s ib le m e c h a n is m o f o p tic fie oflc 3halh. Areti 0]tttia irr. ' 930:3:71-Э
a t r o p h y c h a r a c te r iz e d b y in c re a s e d la te n c y o f v is u a l e v o k e d
8. Еш М & Ш нзрц йCC.М зпйЯЕ.аa. {жЬнщ № к я я r tfveШ & г*! .rrtobf
■iCatfmstcaDec trr печ-е рts. Liphrch'c+njv '&3335:931МВ
re s p o n s e s in f o u r o f i h e m . C o n s u m p t i o n o f b u s h te a, cas­ 9. К ЕйЬЗ i Les nssEfiSs popjdres; dagvsfic d№renlH ш ш й н msculai^i flcai
sava c y a n id e , s y p h ilis , a n d V ita m in d e iic ie n c ie s w e re n o t imliK.ATGttJfil xm .ffi 1-17
'и Геггс /J3.^ a ja f Иаачгет: a s x al# vjflh «ojen ^]l nl эгts n ™ iKcd: идл
s ig n ific a n tly a sso c ia te d . A s m a ll n u m b e r o f p a tie n ts m a y Iri’rqs in trto c a a smJating i ia ia ^ l тйатс^гa of trs d iiia . Adi Озкга irnl
show im p ro v e m e n t in v i s i o n ; m o s t re m a in stable a fte r a ISH^TOcSiC-E?.
' 1 Gass JDM Dк и й л 6f р и г t.-. йосЧ^ггг U O rtt pis xtl ptiteu ransl isa tfireH.
p e r io d o f v is u a l d e t e r io r a t io n ." Iran: Am ^phm^md Ss; 1
An e p id e m ic of optic n e u ro p a th y c h a ra c te ris e d by '■2. jflss J D H Sercus-]f it' t racJ a i s o T i r y !■ (w g -i i a p r cl сp! с т е г^ е з с .
Ал; JCfMiGl-Kri 1'3£5:E7.S21-Il.
b ila te ra l su b a c u te v is u a l lo s s , d y s c h r o m a t o p s ia r cen­
13L £fiKfoi fi. Chif:S ri W. F ix h lt;s oclic fl зс аасй зй: ^ naaJar -ieca-eralicfl. B ' J
tral o r c e c o c e n lra l sco to m a s, fa tig u e , w e ig h t lo s s , a n d in :tflhama lSK)i3:43l-&
som e p a lie n ts p e rip h e ra l n e u ro p a th y, o c c u rrin g p rim a r­
i of M ten BS, Kiarn JC.?a"JtEl P. Орйс nerve ptdfltngpapJedara.flfLii Свтглкш
Ш . №!Й-1С0.
ily in m en, was id e n tifie d in Cuba in 1932 (10 0 0 cases] ' S. - ей k^s = fcLlina - miu-js detd Ji'ST ч; №spi: pii luaed -jis ше^вг. aivd
and I У 93 [4 iJ 0 0 0 ca se s). C ig a re fte s m o k i n g , n u n d rin k ­ амгомрJa! !r"i. La&Ji L ghl CWifia nxii' &Й 2:24lK£
'6 УК. Св'Лз! 5kdjs el nsMlTi :-,!h colic p1к а й Viilh dI cIxsigu alicfl. An J
i n g , c a s s a v a i n g e s t i o n [ it c o n t a i n s v a r i a b l e a m o u n t o lf c y a ­ [fClham ai9e)je7:51^ '
n id e ) a n d v i t a m i n d e fic ie n c ie s , e s p e c ia lly fo iic a c id , w e re '7 ^rc М.*. Pc-pe j J. f i'e . E . JwlaMplbry iu jf iid [B\a:oin л lion associaed -^rt
m jen tai q: ts ir t; пеяч. AmJ Ojriha rrn ' 934:Э(7:еЕЕ-3
i d e n t i f i e d as r i s k f a c t o r s a f f e c t i n g m i t o c h o n d r i a l o x i d a t i v e '3 ^alra F£. anra-WG. 1кта:теса1 liiaieiKr tef seras iraajlii deladiinsr. лтт OctmakiEl
p h o s p h o ry la tio n in this C u b a n e p id e m ic o p tic ne u го р а ­ 197&:£4.-.^2l.
л у -i ( n Sp j l e 0 f t h e f e a t u r e s i n c o m m o n W i t h L H Q H
'9 ^лесрj a Ht). Crater- kte -els г ih; eel с iic n l Milrai гaa-xalt;. Am
фиИ[ш?106ОЙ451^И
m i t o c h o n d r i a l D M A m u t a t i o n s w e r e f o u n d i n f r e q u e n t l y in 20. jih H К Lcf« Я, Kressfl L^d. naaiiifi жхц1яа 'й tt: ® !к ген* pm. Arcti
th e s e p 3 ti jt o a ia ;5CIIjHH H o w e v e r , b o t h m a y share d e p le tio n
ф,М№ 1S63.10a^l-7.
21. -. l^iruni L Srgsrmii L. d a. hipM rtiot hi чa.ol in ria i eher drJaceiwnl sr
o f m ito c h o n d ria l a d e n o s in e trip h o s p h a te in th e ir p a th o ­ !те reufil emr slirc frcn-а я : pi!;, kir- OmTaJ-id 1392:11071-S.
g e n e s is . P a p ilS o m a c u la r b u n d l e [s m a lle s t a x o n s w ilh le ast
22. H3 Rls v oater-l kE b e: ki T-e cisc. A s i 05f:Tafl-n l&S;2iE:-ia&-i3.
23. н&ЗсП^йт L. ole-n S, jm- M. and usap ^ b v teicti; к Ы detadinM
m y e lin ) a n d su ra l n e rv e [lo n g e s t a x o n s re q u irin g lo n g e s t SEOciaiBd'rtti p r d а н с а к CpTlafcict-gica 15 ti^ :l4& :247-5 l.
t r a n s p o r t ) a re m o s t v u ln e r a b l e to t h e c h a lle n g e s o f m i Lo ­
2i luanite п K, Af M. Cavfi tanars of nplt ^ a alt Irani Оз(ЧГа n'ft See U<1^&66
13&-20CI.
c h о E i d r i a l t r a n s p o r t a n d s h o w t h e m o s t d a m a g e as t e m p o ­ 25. i:f.at- - МсОогаИ H I Tralma'J cl reli cl jctaLtmsrl aacc ated wttti -pr. ih л j i
r a l p a l l o r o f t h e d i s c . -1"'' or ocdBTfl. ^hltdioDls^ lS)S5;s&:17&-Щ.
26 iDfcelШ &a!i CF. Fai .C e! a. Umg-teim wiusl ajest -k n calen^ № cflic па'нй al arri
E x p e r i m e n t a l c y a n id e e x p o s u r e in a n im a ls c a u ses d e m y e ie'DJS г1па eedc'f finofТе macja.CpirL'al'n'a'Dgv 1 Щ Э ’ :1Е35-42.
-] i l l a t i o n , and c irc u m s ta n tia l c lin ic a l and la b o r a L o r y e v i­ 27 Cnyte E. Ttkci C. iiflcl P el a. Hidi-ie:c ulicfl apScafHSmce Шк^гар^ ftina'sl'al u-i cf
martiaas :azrnig sadc d it p(!s aid rfstjcmis. 6' J ЗССЙЭЗЖЬЕ.
dence su g g e sts s im ila rity to several hum an c o n d itio n s , 23. XtcartraTi 4 fem naiv <.Jbcnsa1» ^ imp'a^'em of s s a t п'асиирзп^ siskeiwJ wtt;
d e fe c tive c y a n id e m e ta b o lis m m ay be a co m m on p a th in ■3i>3ental cf lie fl sc ni: ai ССГ stuc^. djf. i.L-Dfiflj ЮСЫ ЭЙО-г.
t u b e r ' s a n d o t h e r h e r e d i t a r y o p Lie a t r o p h i e s ( d o m i n a n t a n d
Ж Vetotiani 4 O-n.tt аягс dtics, cf le dj: c c ^ k ii агд pi: al t^trii ais
in/idfl s n 1 aw e eye. AtT OpntEbnol 2>Ж; ?2S.HB-2.
re c e s s iv e ), r e t r o b u lb a r n e u r it is , o p lic a t r o p h y , a n d s u b a c u le 30. EiccWiistFU.CclcprG^c В'Ж!.1! (/relidffllDchTHiL 'aisAKiCthlha'ioDiSac
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