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Entropion 4 PDF
Entropion 4 PDF
Eleventh Edition
Joseph W. Sowka, O.D., FAAO, Dipl. Andrew S. Gurwood, O.D., FAAO, Dipl. Alan G. Kabat, O.D., FAAO
TABLE OF CONTENTS
Eyelids & Adnexa Conjunctiva & Sclera Cornea Uvea & Glaucoma Vitreous & Retina Neuro-Ophthalmic Disease Oculosystemic Disease
Pituitary Adenoma...............................................46
CORNEA
Amaurosis Fugax and Transient Ischemic Attack .....48
Corneal Laceration ..............................................19
Cranial Nerve III Palsy .........................................50
Terrien’s Marginal Degeneration ...........................20
Cranial Nerve IV Palsy ........................................52
Chemical/Toxic Keratoconjunctivitis ......................22
Cranial Nerve VI Palsy ........................................53
Bacterial Keratitis ................................................24
OCULOSYSTEMIC DISEASE
UVEA & GLAUCOMA
Myasthenia Gravis ..............................................56
Axenfeld-Rieger Syndrome ...................................27
Multiple Sclerosis ................................................57
Malignant Glaucoma ..........................................28
Thyroid Ophthalmopathy (Graves’ Disease) ...........60
Crystalline Lens Subluxation .................................29
Albinism.............................................................63
Iridodialysis ........................................................31
A Peer-Reviewed Supplement
The articles in this supplement were subjected to Review of Optometry ’s peer-review process. The maga-
zine employs a double-blind review system for clinical manuscripts. Two referees review each manuscript
before publication. This supplement was edited by the editors of Review of Optometry .
©2009. Reproducing editorial content and photographs require permission from Review of Optometry.
001_ro0409_handbook 4/2/09 9:42 AM Page 5
To Our Colleagues,
This year sees the publication of the eleventh edition of The Handbook of Ocular Disease Management.
The years that we have been compiling this compendium have been professionally very rewarding to us.
We are forever grateful to the management and editorial staff at Review of Optometry. We especially
thank Amy Hellem for her work and contribution. We also thank Alcon for its continued support.
When we first envisioned this supplement, we wanted to provide a quick reference on the most com-
monly encountered ocular diseases and offer readers our perspectives and experience in dealing with
these conditions. However, as the compendium evolved, we quickly saw the need to rely more heavily
on evidence- based medicine. Simply put, evidence-based medicine is the conscientious, explicit, and
judicious use of current best research in making decisions about the care of individual patients. The
practice of evidence- based medicine means integrating individual clinical expertise with the best avail-
able external clinical evidence from systematic research. Good doctors combine individual clinical
expertise with the best available external evidence. Without clinical expertise, practices risk becoming
tyrannized by evidence, for even excellent external evidence may be inapplicable to or inappropriate for
an individual patient. Without current best evidence, a practice risks becoming rapidly out of date, to
the detriment of patients. We have gone back to the beginning. We want to ensure that every condition
that we write about (or have written about) not only reflects our personal experience and perspective, but
that our perspectives are backed through scrupulous research and reflect evidence based medicine.
Last year, we dedicated the Tenth Edition to our professors and mentors who helped shape our profes-
sional development. This year, we dedicate the Eleventh Edition of the Handbook of Ocular Disease
Management to our students and residents. With their interactions and questions, they challenge us to
remain current and practical and to stay on top of our game.
To them we dedicate the eleventh edition of the Handbook of Ocular Disease Management.
Joe
Andy
Al
]
Disease. He is the director of the Glaucoma Service and chief of the Advanced Care
Service. He is a diplomate of the Disease Section of the American Academy of
Optometry (Glaucoma Subsection) and a founding member of the Optometric
Glaucoma Society and the Optometric Retina Society. He can be reached at
(954) 262-1472 or at jsowka@nova.edu.
Andrew S. Gurwood, O.D., F.A.A.O., Dipl., is a member of the attending staff of The
Albert Einstein Medical Center Department of Ophthalmology. Involved in direct patient
care, he also precepts students and medical residents teaching clinical practice, clinical
The authors have
medicine and its relationship to the eye and ocular urgencies and emergencies. He is a
diplomate of the American Academy of Optometry’s Primary Care Section, a founding no financial inter-
member of the Optometric Retina Society, a member of the Optometric Glaucoma
Society and member of the Optometric Dry Eye Society. He serves on the American est in any product
Academy of Optometry’s Program Committee and is the Chairperson of the American mentioned.
Academy of Optometry’s Disease Section Written Examination for Retinal Disease
Diplomate. He can be reached at (215) 276-6134 or at agurwood@salus.edu.
BLOWOUT FRACTURE eral wall is composed of the zygomatic eyeball, causing the globe to strike one of
bone and the greater wing of the sphe- the orbital walls such that it fractures; or
Signs and Symptoms noid; the floor of the orbit is composed 3) The force may be transmitted by the
Blunt trauma to the orbital rim is the of the orbital plate of the maxilla, the globe via the principle of fluid incom-
typical cause of orbital floor and medial zygomatic and orbital process of the pressibility, causing generalized
orbital wall fractures.1-3 Although there pterygopalentine bone; the medial wall increased orbital content pressure or a
is no epidemiologic predilection for “hydraulic” effect, resulting in bone frac-
“blowout fracture,” there are some clini- tures.9-12 The point of breakage usually
cal trends regarding those individuals occurs along the axis of least support in
most likely to sustain these injuries: an area where the tissue is weakest.9-12
male, between the ages of 18–30, Since the orbital floor is not parallel to
engaged in activities of poor judgment, the horizontal plane, the vector of the
with most incidents occurring in or near striking force seems to affect the result-
the home.3,4 The specific term “blowout ant fracture patterns.9 Although all three
fracture” is reserved to connote an iso- mechanisms are mentioned in the liter-
lated orbital floor or medial wall fracture ature, the buckling mechanism and the
in the setting of an intact orbital rim.1-3 hydraulic mechanism seem to have the
Patients present with a history of blunt- most support.10-12 Fractures produced by
force trauma, such as being struck with the buckling mechanism are often lim-
a projectile, like a ball, bat or fist, or ited to the anterior part of the orbital
being a participant in a collision injury, floor.11 In contrast, hydraulic fractures
such as those caused by the impact of an are often larger, involving both the ante-
airbag or the contact of an object fol- rior and posterior parts of the floor as
lowing a fall.5 Pain, photophobia and well as the medial wall of the orbit.11
lacrimation associated with post-trau- CT scan demonstrating a blowout fracture of The orbital floor has a lower thresh-
matic uveal inflammation (iritis or iri- the right orbital floor. old for fracture than the medial wall
docyclitis), variable facial swelling sec- and other orbital bones and occurs most
ondary to fluid or air (orbital of the orbit is composed of maxilla, the frequently. When it gives way, the globe
emphysema), crepitus (a crackling noise lacrimal, the ethmoid and body of the and its attached components become
when tissue infiltrated with air is palpat- sphenoid.7 The other critical anatomi- unsupported, slipping down into the
ed), gaze-evoked diplopia and pain cal players are the surrounding vacant sinus below, producing visible
upon movement of the eyes are all com- paranasal air sinuses.8 Several sinuses enophthalmos and gaze-evoked, symp-
mon.6 Other associated collateral surrounding the orbit help to lessen the tomatic diplopia, along with degrees of
injuries may include subconjunctival weight of the skull and aid in the reso- extraocular muscle dysfunction and
hemorrhage, ruptured globe, corneal nance of the voice.8 Unfortunately, infraorbital nerve hypoesthesia.10,12
abrasion, conjunctival laceration, hyphe- these structures leave the superior,
ma, iridodialysis, lenticular subluxation, medial and inferior walls of the orbit Management
retinal detachment, vitreous hemor- unsupported and vulnerable to cata- For the optometrist, the treatment of
rhage, choroidal rupture and optic nerve strophic failure (blowout fracture, trap blowout fracture centers around ocular
avulsion. If the eye settles inferiorly or door fracture) from blunt-force trauma. first aid. The most challenging aspect of
medially into the exposed sinus, enoph- The sinuses surrounding the orbit beginning an examination on patients
thalmos with restricted ocular motility include the ethmoidal air cells (anterior, who have experienced facial blunt-force
will be present, with or without loss of middle and posterior), the sphenoidal injury is getting the eye open to look.
facial sensation. sinuses, the maxillary sinuses and the Facial and orbital swelling or orbital
frontal sinuses.7,8 emphysema can literally force the eye
Pathophysiology There is some debate about the closed. In such cases, a Desmarre lid
The seven bones of the orbit include mechanism of blowout fracture. When a retractor can be used as a speculum to lift
the frontal, zygomatic, maxillary, eth- blunt force impacts the face, it may pro- the superior lid. The thin blade can be
moid, sphenoid, lacrimal and ptery- duce a combination of effects: 1) The inserted between the lids and the superi-
gopalentine.7 The orbital roof includes force may strike the bone, producing a or lid elevated by pulling upward.
the orbital plate of the frontal bone and shock wave that causes “bone buckling”; Since blunt ocular trauma involving
the lesser wing of the sphenoid; the lat- 2) The force may be transmitted to the the eye or face is the result of being
aponeurogenic, myogenic, neurogenic genic ptosis implicates either the levator function and pupillary responses.
or mechanical.1 via oculomotor palsy (i.e., cranial nerve Pseudoptosis—any condition that gives
Aponeurogenic or involutional ptosis III palsy) or the muscle of Mueller via the appearance of a drooped lid but actu-
is the most commonly encountered form oculosympathetic dysfunction (i.e., ally involves no lid dysfunction in the
of acquired ptosis, particularly in older Horner’s syndrome). Occasionally, how- involved eye—must be ruled out. Some
ever, neurogenic ptosis results examples of pseudoptosis include
from a lesion to the supranuclear patients with small globes (e.g.,
pathway, a condition referred to microphthalmos, phthisis bulbi), enoph-
as apraxia of eyelid opening. This thalmos, blowout fracture, contralateral
bilateral ptosis is characterized by lid retraction and ipsilateral hypotropia.
inability to open closed lids vol- Mechanical etiologies are the simplest to
untarily, and it may be seen in remedy, in principle: Removal of the
patients with extrapyramidal dys- cause creating the resistance should ren-
function, including progressive der improvement. In cases of extensive
supranuclear palsy, Parkinson’s scarring from long-standing disease, a
disease, Shy-Drager syndrome, surgical consultation may be advised.14
and Wilson’s disease.11 Aponeurogenic ptoses may be treated
Involutional ptosis in an elderly patient. Mechanical ptosis can be by a variety of methods. The use of a
caused by any condition that pro- prosthetic ptosis crutch attached to the
adults.1 It involves local dehiscence, vides resistance to the action of the leva- spectacle frame can provide relief from
stretching and disinsertion of the levator tor muscle. The most common etiologies some of the major symptoms encoun-
aponeurosis from its attachments to the include trauma, lid tumors, dermatocha- tered by these patients. The principle
tarsus and pretarsal orbicularis muscle.2 advantage of this modality is
Histologic evaluation of the patient diminished cost without the risks
demonstrates atrophy, fatty infiltration of surgical intervention.15 Of
and fibrosis of the levator muscle, as well course, surgery offers a more con-
as an attenuated levator aponeurosis.3 sistent and long-term solution for
Although elderly patients are primarily patients with ptosis. Procedures
affected, younger patients can develop such as levator resection and
this condition as a result of trauma, aponeurosis tightening are prin-
severe lid swelling, blepharochalasis, ciple considerations. All surgical
prior ocular surgery or long-term contact patients should be followed
lens wear.4-6 closely for the development of
Myogenic ptosis is less commonly secondary lagophthalmos and
encountered clinically than aponeuro- Mechanical ptosis resulting from trauma to the lid. exposure complications.14
genic ptosis. It results from one of a Ptosis that is neurogenic or
number of muscular debilities involving lasis and conjunctival scarring (i.e., sec- myogenic in nature is best managed by a
the levator palpebrae superioris. ondary to ocular cicatricial pemphigoid specialist with advanced training in
Etiologies include acquired mitochondr- or Stevens-Johnson syndrome). Floppy neuro-ophthalmology. Such cases gener-
ial dysfunction (chronic progressive eyelid syndrome also falls within this ally require imaging and other special-
external ophthalmoplegia), muscle fibro- category. Excessive papillary responses, ized testing (e.g. Tensilon® in myasthe-
sis and degeneration (myotonic dystro- such as vernal keratoconjunctivitis or nia gravis) for confirmatory diagnosis.
phy and oculopharyngeal dystrophy) and giant papillary conjunctivitis, can also
dysfunction of neuromuscular junction result in mechanical eyelid ptosis.1,12,13 Clinical Pearls
signaling due to acetylcholine receptor • Consider the lid crease when differ-
autoantibodies (myasthenia gravis).1,7-10 Management entiating congenital ptosis from acquired
Neurogenic ptosis involves a disrup- Without question, the most impor- ptosis. Acquired ptosis will maintain a
tion of innervation to the muscles of tant aspect of managing a patient with lid crease; congenital ptosis will not. A
eyelid elevation. There are various eti- acquired ptosis is determining the high lid crease often heralds an aponeu-
ologies, including vascular ischemia, underlying cause. A thorough history is rogenic ptosis.
inflammation, infection, demyelination crucial. The clinician must consider lat- • Review of old photographs of the
and neoplasia. Most commonly, neuro- erality and check associated motility patient may also often help to differenti-
different type of disease state compared transient paralysis of the eyelid protrac- anatomical position within 1 or 2 sec-
with the other three categories. It tor muscles, botulinum toxin may help onds before blinking, it is indicative of
occurs when the preseptal orbicularis to alleviate the inward turning of the lid pathological laxity.1 Another diagnostic
muscle becomes overactive and hyper- margin for several weeks, until surgical technique is the dislocation or distrac-
trophic secondarily to blepharospasm, intervention can be undertaken. In tion test. This is performed by grasping
inflammation, irritation or surgery.1 In cases of spastic entropion, the injection the lower eyelid and pulling it anterior-
addition, some degree of eyelid edema is of botulinum toxin into the orbicularis ly away from the globe. If the lid can be
also present; this adds to the abnormal muscle may break the cycle of spasm pulled more than 7mm from the globe,
mechanical forces turning the margin and irritation.10 then increased horizontal lid laxity is the
inward. Unlike the other forms of entro- Surgery provides the longest-lasting source of the entropion.1
pion, spastic entropion typically resolves solution and is ultimately the best • The easiest way to resolve spastic
when the underlying inflammatory or therapeutic option in most cases of entropion is to remove the offending
irritative factors are eliminated.5 entropion. In cicatricial cases, surgical irritant. In cases that involve the seventh
repair may include excision of the scar cranial nerve (essential blepharospasm,
Management with a tarsal plate graft from preserved orofacial dyskinesia, hemifacial spasm,
While the treatment of choice sclera, ear cartilage or hard palate (in facial myokymia) a neuro-ophthalmic
should be guided by the underlying most severe circumstances), along with consult is indicated. In some instances,
cause, the fundamental philosophies of conjunctival and mucous membrane these conditions can be managed phar-
entropion management include: 1) grafting using fetal amniotic mem- macologically using anti-seizure med-
moving the lid margins and lashes brane tissue.2 For involutional entropi- ications.
away from the cornea, and 2) providing on, common surgical options include • Thermal cautery of the lid was
lubrication for the compromised ocular the Quickert suturing technique or a once a popular corrective procedure for
surface. A simple method for alleviat- base-down triangular tarsal resection. the treatment of involutional entropion;
ing contact between the eyelid and If significant horizontal lid laxity is however, this technique appears to have
ocular surface is to apply surgical tape present, then a combination technique fallen out of favor over the last 10 to 20
to the lid to rotate it out and away from involving horizontal shortening of the years, particularly among oculoplastic
the globe. Unfortunately, this tech- eyelid and resuspension of the lower surgeons.2
nique is neither precise nor permanent, eyelid retractors may be performed.1,2,11
and it requires cooperation and partic- 1. Skorin L Jr. A review of entropion and its manage-
ment. Cont Lens Anterior Eye 2003;26(2):95-100.
ipation by the patient. It is typically Clinical Pearls 2. Eliasoph I. Current techniques of entropion and
employed as a stopgap measure for • A thorough history should be com- ectropion correction. Otolaryngol Clin North Am
individuals who are not amenable to pleted for all patients with entropion. 2005;38(5):903-19.
3. Vallabhanath P, Carter SR. Ectropion and entropion.
prompt surgical intervention. The lib- Attention to previous eye surgery, trau- Curr Opin Ophthalmol 2000;11(5):345-51.
eral use of artificial tear products is rec- ma, chemical injury, chronic infection 4. Piskiniene R. Eyelid malposition: Lower lid entropion
ommended for all entropion patients, and changes in eyelid tonus should be and ectropion. Medicina (Kaunas) 2006;42(11):881-4.
5. Choo PH. Distichiasis, trichiasis, and entropion:
regardless of the etiology; gel-forming provided. Advances in management. Int Ophthalmol Clin
solutions, gels and ointments may pro- • The differential diagnosis of 2002;42(2):75-87.
vide greater and more sustained relief entropion includes eyelash anomalies 6. Carter SR, Chang J, Aguilar GL, et al. Involutional
entropion and ectropion of the Asian lower eyelid.
of symptoms than drops. Bandage con- such as trichiasis (inward turning of the Ophthalmic Plast Reconstr Surg 2000;16(1):45-9.
tact lenses may also prove helpful in cilia) and distichiasis (multiple rows of 7. Montero J, Sparholt J, Mély R, et al. Retrospective
providing a barrier between the ocular eyelashes), neuro-ophthalmic blepharo- case series of therapeutic applications of lotrafilcon a
silicone hydrogel soft contact lenses. Eye Contact Lens
surface and entropic lid margin.7 spasm, traumatic etiologies, scarring 2003;29(2):72-5.
Prophylactic antibiotic coverage may from chemical injuries and lid mal- 8. Christiansen G, Mohney BG, Baratz KH, et al.
be beneficial in cases of more severe position secondary to previous ocular Botulinum toxin for the treatment of congenital entropi-
on. Am J Ophthalmol 2004;138(1):153-5.
keratitis. In lieu of bacitracin or ery- surgeries. 9. Steel DH, Hoh HB, Harrad RA, et al. Botulinum toxin
thromicin ointment q.i.d., AzaSite® • Focused physical testing can aid in for the temporary treatment of involutional lower lid
(azithromycin 1% in DuraSite®) offers the diagnosis of entropion. One such entropion: A clinical and morphological study. Eye
1997;11(Pt 4):472-5.
a similar antimicrobial spectrum and examination technique is the “snap-back 10. Wabbels B, Förl M. [Botulinum toxin treatment for
efficacy at just once-daily dosing. test,” in which the patient is asked to crocodile tears, spastic entropion and for dysthyroid
Botulinum toxin has been shown in look upward slightly while the examiner upper eyelid retraction]. Ophthalmologe
2007;104(9):771-6.
several series to provide temporary pulls the lower eyelid inferiorly; if the 11. Quickert MH, Rathbun E. Suture repair of entropi-
relief of entropion.8-10 By affecting a eyelid fails to return to its normal on. Arch Ophthalmol 1971;85(3):304-5.
the known serotypes.11 As with many lar papillomas and other benign skin spread to form satellite lesions around
viral diseases, patients who are lesions. Application of these agents is the eye, affect skin in different regions of
immunocompromised by chronic dis- simple and safe, provided the sur- the body or be transferred to other indi-
ease (diabetes, HIV infection, and so rounding skin is coated with petrole- viduals. HPV is often spread by sexual
on) are more susceptible to infection. um ointment and the chemicals are contact; patients should be asked
Squamous papillomas may have not applied on the lid margin or con- whether similar lesions exist elsewhere
numerous etiologies, but most often junctival surface. Cryotherapy with on the body; if so, appropriate referrals
they arise de novo as a normal senescent liquid nitrogen is another common should be made.
skin change. The onset tends to be grad- treatment modality for papillomas, • Some states permit optometrists to
ual rather than sudden. Lesions tend not although this is typically not used out- remove benign skin lesions via chemical
to resolve spontaneously, nor is acute side of a dermatologist’s office. cautery. The Derma-Cauter-All® Chem-
enlargement common. However, squa- Recently, however, over-the-counter ical Cauterization Kit is available to eye-
mous papillomas may in rare instances cryogens such as Verruca-Freeze® care practitioners and includes all of the
represent precancerous lesions, so (CryoSurgery, Inc., Nashville, TN) necessary items to perform in-office
malignant conversion must remain a have made it possible for other health chemical cautery (dichloracetic acid,
consideration.12 professionals to employ this technique. petrolatum, cleaning pads, acid recepta-
Again, exercise caution when using cle, applicators, dropper and an instruc-
Management cryotherapy on periocular lesions; tion packet with a DVD).14 The kit may
Because of their benign nature, ver- adverse effects can include hypo- or be ordered online from Sigma Pharma-
ruca and squamous papillomas typically hyperpigmentation (especially in dark ceuticals, LLC (www.sigmapharmaceuti-
warrant intervention only in cases of skin) as well as nerve damage when cals.com) or from North Pine Enterprises
cosmetic concern, impairment of lid therapy is too aggressive.12 Inadvertent (www.northpineenterprises.com).
function or discomfort. Obviously, application of cryogens to the ocular
1. Dutton JJ, Gayre GS, Proia AD. Papilloma. In:
should any signs suggestive of of malig- surface can result in corneal scarring, Dutton JJ, Gayre GS, Proia AD, eds. Diagnostic Atlas of
nancy develop, biopsy and removal are scleritis, uveitis and a host of other Common Eyelid Diseases. New York: CRC Press,
essential. Typical management involves complications. 2007, pp. 225-6.
2. Dutton JJ, Gayre GS, Proia AD. Verruca vulgaris. In:
patient reassurance, photodocumenta- Other treatment options for periocu- Dutton JJ, Gayre GS, Proia AD, eds. Diagnostic Atlas of
tion and periodic observation. lar papillomas include laser ablation Common Eyelid Diseases. New York: CRC Press,
When warranted, papillomas may using the CO2 laser, Nd:YAG laser or 2007, pp. 258-60.
3. Welch JL, Edison KE. Treatment options for the
be removed via several methods. pulsed dye laser.13 Verrucae may also common wart. Mo Med 2007;104(6):502-5.
Electrocautery and surgical curettage respond to a number of topical therapies, 4. Lio P. Warts, molluscum and things that go bump on
are some of the oldest and still most including cantharadin, podophyllin, the skin: A practical guide. Arch Dis Child Educ Pract
Ed 2007;92(4):ep119-24.
widely practiced therapeutic options bleomycin and imiquimod. 5. Miller DM, Brodell RT, Levine MR. The conjunctival
for both ocular and non-ocular wart: Report of a case and review of treatment options.
lesions.13 The application of electric Clinical Pearls Ophthalmic Surg 1994;25(8):545-8.
6. Pariser RJ. Benign neoplasms of the skin. Med Clin
current results in iatrogenic necrosis • Although the nomenclature regard- North Am 1998;82(6):1285-307,v-vi.
and subsequent regression, usually ing papillomas is sometimes confusing 7. Bellew SG, Quartarolo N, Janniger CK. Childhood
within a week to 10 days. Unfor- and contradictory, the terms all refer to warts: an update. Cutis 2004;73(6):379-84.
8. Ciconte A, Campbell J, Tabrizi S, et al. Warts are not
tunately, both electrocautery and benign epithelial lesions. merely blemishes on the skin: a study on the morbidity
curettage can be painful unless local • Whether the origin is hyperplasia associated with having viral cutaneous warts. Australas
anesthesia is used, and they can result or viral infection, recognition and differ- J Dermatol 2003;44(3):169-73.
9. D’hermies F, Morel X, Bourgade JM, et al.
in cosmetically displeasing scarring. entiation from malignant skin lesions is Hyperkeratosis papilloma of the eyelid. An anatomic
Additionally, physicians must take care the first concern. Red flags for malig- clinical case. J Fr Ophtalmol 2001;24(5):558-61.
when surgically removing verrucae to nancy include the following: asymmetry 10. Steigleder GK. Histology of benign virus induced
tumors of the skin. J Cutan Pathol 1978;5(2):45-52.
prevent spread of the virus by cutting of shape, irregular borders, abrupt 11. Jablonska S. Wart viruses: human papilloma virus-
across the stalk of pedunculated changes in coloration or size, crusting or es. Semin Dermatol 1984;3(2):120-9.
lesions. The virus may also spread if bleeding with minimal manipulation. 12. Schwartz RA, Tarlow MM, Lambert WC.
Keratoacanthoma-like squamous cell carcinoma within
not enough of the adjacent tissue is Rarely, malignant lesions may arise from the fibroepithelial polyp. Dermatol Surg 2004;30(2 Pt
removed. or adjacent to benign papillomas.12 2):349-50.
Chemical cautery with trichlo- • Patients should be advised of the 13. Lipke MM. An armamentarium of wart treatments.
Clin Med Res 2006;4(4):273-93.
racetic or dichloracetic acid is a popu- infectious nature of verrucae. They 14. Napper G, Douglas I, Albietz J. Ocular therapeu-
lar therapeutic alternative for periocu- should be educated that these may tics. Clin Exp Optom 2007;90(3):212-3.
rapidly growing mass lesions of the Organization (WHO) classification, proven lymphoma deserve a complete
superficial ocular surface. They can be established in 2001.6,7 This system rec- medical evaluation to determine
seen as isolated entities or they may ognizes three broad categories: precur- whether systemic lymphoma is present.
occur as a localized manifestation of sor cell lymphomas, peripheral B-cell This includes basic hematology (CBC
systemic lymphoma.1,2 The typical neoplasms and peripheral T and NK with differential) as well as evaluation
appearance is that of a pink, “fleshy” cell neoplasms. It further subdivides by an oncologist. Radiographic imag-
mass that arises from within the fornix these into numerous specific entities ing of the head, chest and abdomen
and extends toward the cornea; classi- based upon morphologic, immunologic should also be obtained if systemic
cally, they are described as “salmon-col- and genetic characteristics.6,7 involvement is suspected.9
ored patches.” They may present bilat- Therapy for conjuncti-
erally in 20% to 38% of patients.2-4 val lymphoma depends
Individuals with conjunctival lym- on the disposition of the
phoma are usually between 60 to 68 tumor and whether there
years; the condition predominantly is disseminated lym-
affects female patients.2-5 These phoma elsewhere in the
patients may have cosmetic concerns body. Isolated conjuncti-
regarding chronic redness, and they val lymphoma (i.e.,
occasionally report dryness and irrita- involving the conjunctiva
tion, but they rarely experience sub- but not other ocular or sys-
stantial ocular discomfort. Vision may temic structures) is often
be variably impacted, depending upon treated with external beam
the location and extent of the lesion. irradiation, on the order of
2,000–4,000cGy.2,10 Dos-
Pathophysiology MALT lymphoma. age and exposure tends
Lymphoid tissue is present in most to be higher for more
organs throughout the body. It is con- Most conjunctival lymphomas fall aggressive non-MALT lymphomas,
nected by channels and conduits to into the category of B-cell neoplasms although care must be taken to mini-
lymph nodes, located primarily in the of the non-Hodgkin’s variety.6,8 These mize long-term complications of ocu-
neck, axillae, groin and abdomen. are frequently broken down further lar radiation such as xerophthalmia or
Lymphoma is an abnormal, malignant into mucosa-associated lymphoid tis- cataract formation.11 Other therapeutic
growth of lymphoid tissue; a cancer of sue (MALT) lymphomas and non- options for these patients may include
the various elements of the lymphatic MALT lymphomas. MALT lym- brachytherapy, cryotherapy, intrale-
system. In the eye, lymphoma typical- phomas generally follow a more sional interferon-A, rituximab or sim-
ly manifests as a conjunctival or orbital indolent course; non-MALT lesions ple observation.10,12,13 Those with inva-
mass; less common presentations are considered highly malignant and sive or disseminated lymphoma may
include choroidal infiltration with sec- invasive.9 require systemic chemotherapy in
ondary uveitis and infiltrative optic addition to local treatment. The stan-
neuropathy.3 Management dard regimen for non-Hodgkin’s lym-
Over the years, a number of classifi- Although conjunctival lymphomas phoma is a combination of cyclophos-
cation systems have been developed to often have a characteristic appearance, phamide, doxorubicin, vincristine and
describe lymphoid tumors. These it is important to differentiate them prednisone, referred to in oncologic
include the Rappaport, Kiel, Lukes- from other benign tumors of the ocular circles as CHOP.14,15
Collins, Working Formulation, British surface, such as squamous papilloma,
National Lymphoma Investigation, pyogenic granuloma and lymphangiec- Clinical Pearls
and Revised European-American tasis. Furthermore, it is not possible to • Conjunctival lymphoma should be
Lymphoma (REAL) classifications.6 differentiate between benign and part of the differential in all cases of
These systems were based on the histo- malignant lymphoid tumors (or sudden-onset rapidly growing lesions
logical appearance of tumor growth MALT vs. non-MALT lymphomas) of the fornix, particularly those that are
(nodular or diffuse), size of cells (small, simply on the basis of clinical presenta- highly vascularized and fleshy. Never
medium or large) and cell immunophe- tion. Hence, excisional biopsy is crucial assume that these lesions are benign;
notype (B, T, NK or null).6 Today, the to establish a definitive diagnosis. In the most prudent course of action is to
accepted standard is the World Health addition, any patients with biopsy- obtain a prompt biopsy.
CORNEA
CORNEA
Corneal lacerations are invariably include corectopia (i.e., irregularity of quent extrusion of intraocular contents
accompanied by a recent history of ocu- the pupil) and iris prolapse into or through the wound or introduction of
lar trauma. Typically, this involves a through the wound. Accompanying harmful debris. As the pressure in the
sharp object such as a pathology related to the anterior chamber drops, the pressure
knife, hand tool or glass inciting trauma is also from the vitreous body forces the lens
shard, although cases common; subconjuncti- and iris forward. Excessive manipula-
have been documented val hemorrhage, hyphe- tion or further trauma may induce a
involving some very ma, iridodialysis, lens prolapse of these tissues through the
obscure etiologies, dislocation, cataract, vit- laceration. An additional risk is the
including such odd reous hemorrhage and transmission of potential pathogens
items as fish hooks, plas- Repaired corneal laceration with vitreous incarceration into the eye, resulting in infection.
tic toys, ninja stars and interrupted sutures. are all possible findings.4 Numerous cases of endophthalmitis
the talons from a bird of have been documented, in some cases
prey.1-4 Lacerations may also result from Pathophysiology involving highly unusual organisms.7-9
penetration by a high-velocity projectile The cornea possesses great tensile
or may occur secondary to severe blunt strength and is generally resistant to Management
injury.5 Patients with corneal laceration penetration by blunt perpendicular From a primary care point of view,
typically report intense pain at the forces; however, tangential injuries of the management of corneal laceration
onset, although this may diminish over sufficient force—particularly those involves first aid. The clinician must
time due to severing of the corneal induced by sharp objects—have the make a definitive diagnosis as quickly as
nerves. Additional symptoms may potential to cause the lamellar sheets of possible using the least amount of
include photophobia, excessive lacrima- the corneal stroma to separate, allowing manipulation or intervention. It is most
tion and variably reduced vision. for entry into the tissue. By definition, a important to differentiate corneal abra-
Inspection of the eye reveals pro- laceration refers to a wound produced sions and partial-thickness lacerations
nounced ocular injection, secondary by the tearing of a bodily tissue; it is from full-thickness lacerations. This is
blepharospasm and pseudoptosis sec- usually traumatic, irregularly shaped facilitated by using the Seidel’s test.
ondary to pain and photophobia. The and induced unintentionally by a for- Here sodium fluorescein is applied
corneal laceration may be obvious if it is eign object.6 Lacerations may vary in directly to the wound, and then careful-
large or irregularly shaped. One may thickness. When the cornea is penetrat- ly inspected under cobalt blue illumina-
observe a jagged defect that extends tion. In cases of corneal
from the corneal epithelium into and perforation, aqueous
through the underlying stroma. Small, will slowly percolate
linear breaks may be more difficult to from the lesion, creating
visualize, because the opposing surfaces a dark-appearing area
of the wound may close like a “flap- with a steady flow of
valve” under the sustained intraocular fluid to the inferior flu-
pressure of the eye. If the laceration is orescent tear lake.
full thickness, the anterior chamber Tonometry, gonioscopy
may be shallow or even flat, again and other procedures
depending upon the extent of the requiring pressure on
injury. Aqueous can be visualized per- the globe should be
colating from the edge of the wound deferred if there is any
when fluorescein is applied (Seidel’s suspicion of potential
sign). The intraocular pressure will be Acute corneal laceration due to screwdriver injury. ocular perforation.
substantially reduced in cases of full- To facilitate exami-
thickness laceration, sometimes reach- ed through all layers into the anterior nation in cases of corneal trauma, it is
ing as low as 0-2mm Hg depending chamber, it is referred to as a full-thick- often advantageous to instill a topical
upon the timing of the evaluation com- ness laceration. A cleft that does not anesthetic. This helps to alleviate
pared to the time of injury. completely traverse the stroma and patient discomfort and permits the cli-
One finding that is particularly diag- endothelium is considered a partial- nician to perform a more thorough
evaluation of the eye, including visual more likely in males than females, and dispersed lens fragments. J Cataract Refract Surg
2007;33(4):739-40.
acuity assessment, pupillary evaluation are also more common in younger age 10. Hamill MB. Cornea. In: Kuhn F, Pieramici DJ, eds.
and biomicroscopy. The downside of groups.11 Ocular Trauma: Principles and Practice. New York:
using a topical anesthetic—or any topi- • Although fingernail scratches typi- Thieme, 2002, pp. 95-109.
11. Hamill MB. Corneal and scleral trauma.
cal agent—in cases of corneal laceration cally do not generate enough force to Ophthalmol Clin North Am 2002;15(2):185-94.
is the potential for deep tissue toxicity lacerate the cornea, at least one case of 12. Taneja S, Arora R, Yadava U. Fingernail trauma
or introduced infection. With a com- this has been documented in the litera- causing corneal laceration and intraocular cilia. Arch
Ophthalmol 1998;116(4):530-1.
promised cornea, topically applied ture; hence, it is important to rule out
drugs achieve intraocular concentra- laceration in all cases of corneal trauma.12
tions much greater than normally • With a corneal laceration, the TERRIEN’S MARGINAL
intended. This can lead to unwanted patient may be lacrimating so heavily as DEGENERATION
sequelae. Hence, any topical agents to render the Seidel test inaccurate. In
should be used sparingly if at all, and these cases, a shallow or flat anterior Signs and Symptoms
preservative-free options, where avail- chamber or the presence of bubbles Terrien’s marginal degeneration
able, are preferred.10 within the anterior chamber indicates a (TMD) is a rare, slowly progressive
Once the diagnosis is established, breach in the corneal integrity. thinning disorder of the cornea. The
the primary goal is to stabilize the eye • For full-thickness corneal lacera- condition is typically bilateral and pre-
and ensure that no further damage tions, the less done in the office the bet- dominantly affects men aged 40 years
occurs. An eye shield should be gently ter. Assess the injury, arrange for the and older, although women and
placed to protect the globe; however, appropriate referral and shield the eye younger patients may also present with
the use of a pressure patch or bandage gently for protection while the patient a variant of this condition.1-3 Individuals
contact lens is ill-advised, primarily is in transit to the surgeon. with TMD generally do not exhibit
due to the manipulation required to • The patient should be educated pain, photophobia, lacrimation or con-
apply these measures. In the event that that the initial entering acuity may rep- junctival redness upon presentation. In
material is lodged in the wound, it resent the best vision that can be fact, aside from possible visual changes
should not be removed. Immediately expected after surgical repair. Of course, (resulting from increased regular and
refer to a corneal specialist to initiate visual acuity may improve following irregular astigmatism), these patients
surgical repair of the laceration. surgery; however, it is best not to ele- are often asymptomatic.
Patients must be instructed not to eat vate a patient’s expectations. In its earliest stages, TMD presents
or drink before the surgical consulta- • A fresh, previously unopened bot- as a fine, white punctate opacification of
tion, because this may delay the proce- tle of topical anesthetic is preferred the peripheral cornea. As in arcus
dure. If the patient is nauseous or over- when a full thickness corneal laceration senilis, a clear zone is preserved between
ly anxious, consider prescribing an or globe rupture is suspected. the limbus and the affected region of the
antiemetic agent such as meclizine 25 cornea, although this area may be
mg p.o. to prevent vomiting. 1. Muller L, Kohnen T. Scleral and corneal laceration bridged by fine vascularization resem-
Repair of corneal lacerations involves with iris prolapse caused by an eagle claw. Graefes bling pannus. The proximal edge of the
Arch Clin Exp Ophthalmol 2005;243(4):377-9.
a variety of measures. Partial-thickness 2. Alfaro DV 3rd, Jablon EP, Rodriguez Fontal M, et al. degeneration is demarcated by a circum-
and self-sealing lacerations may be Fishing-related ocular trauma. Am J Ophthalmol ferential yellow line, representing lipid
treated with nothing more than topical 2005;139(3):488-92. infiltration.4 Although these changes
3. Jeng BH, Steinemann TL, Henry P, et al. Severe
antibiotics, cycloplegics and a bandage penetrating ocular injury from ninja stars in two children. can be noted anywhere along the
contact lens. Larger wounds or those Ophthalmic Surg Lasers 2001;32(4):336-7. corneal periphery, the superior and
that are prone to leakage may some- 4. Segev F, Assia EI, Harizman N, et al. Corneal lacer- superonasal aspects of the cornea are
ation by sharp objects in children seven years of age
times be managed with cyanoacrylate and younger. Cornea 2007;26(3):319-23. characteristically involved. Over time,
tissue adhesive in lieu of surgical 5. Baker RS, Flowers CW Jr, Singh P, et al. the region undergoes stromal thinning
repair.11 However, most corneal lacera- Corneoscleral laceration caused by air-bag trauma. Am such that the area resembles a sloping
J Ophthalmol 1996;121(6):709-11.
tions—certainly most full-thickness 6. Dorland WA. Dorland’s Illustrated Medical Dictionary “gutter” with a peripheral lip defined by
lacerations—require suturing to restore (31st ed.). Philadelphia: Saunders, 2007. the corneal limbus.2,5 Despite the loss of
corneal integrity. 7. Ryan EH Jr, Cameron JD, Carpel E. Intraocular mol- corneal tissue, the overlying epithelium
luscum contagiosum after a corneoscleral laceration.
Am J Ophthalmol 1997;124(4):560-1. remains intact.5 Late changes may
Clinical Pearls 8. Sharma S, Saffra NA, Chapnick EK. Post traumatic include localized corneal ectasia,
• According to the database of the polymicrobial endophthalmitis, including Neisseria sub- hydrops and opacification. Perforation is
flava. Am J Ophthalmol 2003;136(3):554-5.
United States Eye Injury Registry 9. Moinfar N, Smiddy WE, Miller D, et al. Posttraumatic a rare sequela, encountered in only
(USEIR), corneal injuries are five times Aspergillus terreus endophthalmitis masquerading as about 15% of cases; although the major-
ity of these complications are due to corneal steepening 90° away from the polyarteritis nodosa)—bilateral, typical-
coincident trauma, spontaneous perfo- area of flattening, with a relatively ly painful and progressive to perforation
ration has been encountered in TMD.1,3 spherical and regular central area.11 • Mooren’s ulcer—unilateral or
CORNEA
Therapeutic management of bilateral, painful corneal thinning with
Pathophysiology Terrien’s marginal degeneration is neovascularization.
The precise etiology of TMD has largely supportive, as the majority of • Pellucid marginal degeneration—
never been fully elucidated; however, patients remain asymptomatic. TMD painless, inferior, peripheral corneal
the disorder has been loosely associated patients are known to suffer from peri- thinning, a variant of keratoconus.
with vernal keratoconjunctivitis, poste- odic episodes of red, irritated eyes sec- • Furrow degeneration—painless,
rior polymorphous dystrophy and ery- ondary to mild adjacent conjunctival peripheral corneal thinning adjacent to
inflammation. In addition to corneal arcus, without vascularization.
lubrication with artificial tears, • Dellen—reversible, painless oval
these cases often respond effec- thinning secondary to corneal dehydra-
tively to topical corticosteroid tion.
therapy (e.g., prednisolone • Marginal keratitis secondary to
acetate 0.12 % or 1%, lotepred- staphylococcal hypersensitivity—pain-
nol 0.5% q.i.d.). Refractive cor- ful, infiltrate present, inset from limbus.
rection is paramount to com- • Fuch’s Marginal Keratitis—
pensate for the acquired peripheral corneal inflammation
astigmatism, although this can marked by pannus and thinning.
be difficult because of the irreg-
1. Srinivasan S, Murphy CC, Fisher AC, et al. Terrien
ularity and severity of the dis- marginal degeneration presenting with spontaneous
turbance. Contact lenses may corneal perforation. Cornea 2006;25(8):977-80.
Terrien’s marginal degeneration. offer a better option for visual 2. Austin P, Brown SI. Inflammatory Terrien’s marginal
corneal disease. Am J Ophthalmol 1981;92(2):189-92.
success, but they often require 3. Beauchamp GR. Terrien’s marginal corneal degen-
thema elevatum diutinum (a rare complex fitting techniques (e.g., piggy- eration. J Pediatr Ophthalmol Strabis 1982;19(2):97-9.
chronic skin disease with cutaneous back lens systems) by trained special- 4. Guyer DR, Barraquer J, McDonnell PJ, et al.
Terrien’s marginal degeneration: Clinicopathologic case
vasculitis), suggesting a possible autoim- ists. Because patients with severe TMD reports. Graefes Arch Clin Exp Ophthalmol
mune mechanism.6-8 Studies have are at risk for corneal perforation, poly- 1987;225(1):19-27.
demonstrated evidence of increased carbonate spectacles are highly recom- 5. Pesudovs K. Terrien’s marginal degeneration: Case
reports and literature review. Clin Exp Optom
lysosomal activity.9,10 Histopathologi- mended, even in cases where contact 1994;77(3):97-104.
cally, the principle findings include lenses are the primary refractive correc- 6. Kremer I. Terrien’s marginal degeneration associated
fibrosis, vascularization and phagocyto- tion. When vision cannot be corrected with vernal conjunctivitis. Am J Ophthalmol 1991;15;
111(4):517-8.
sis of corneal stromal collagen by histi- or the risk of perforation is high, surgi- 7. Wagoner MD, Teichmann KD. Terrien’s marginal
ocytes.9 The epithelium remains intact, cal intervention may need to be consid- degeneration associated with posterior polymorphous
but there is degeneration of basal ered. A variety of procedures have been dystrophy. Cornea 1999;18(5):612-5.
8. Shimazaki J, Yang HY, Shimmura S, et al. Terrien’s
epithelial cells and an abnormal base- employed with modest success, includ- marginal degeneration associated with erythema eleva-
ment membrane-like layer. Bowman’s ing thermokeratoplasty, annular full tum diutinum. Cornea 1998;17(3):342-4.
membrane is typically lost; Descemet’s thickness penetrating keratoplasty, 9. Süveges J, Léval G, Alberth B. Pathology of Terrien’s
disease. Histochemical and electron microscopic study.
membrane may be intact, thickened or lamellar penetrating keratoplasty, and Am J Ophthalmol 1972;74(6):1191-200.
thinned, and sometimes appears wavy. large eccentric corneal grafts.12-14 10. Hayasaka S, Tsuchiya M, Sekimoto M, et al.
The endothelium may be normal or Lysosomal enzymes in tear fluids from patients with
Terrien’s marginal corneal degeneration. Graefes Arch
attenuated.9 Clinical Pearls Clin Exp Ophthalmol 1987;225(5):335-7.
• Suspect Terrien’s marginal degen- 11. Wilson SE, Lin DT, Klyce SD, et al. Terrien’s mar-
Management eration in cases of bilateral or asym- ginal degeneration: Corneal topography. Refract
Corneal Surg 1990;6(1):15-20.
The most important aspect of man- metrical peripheral corneal thinning in 12. Cheng CL, Theng JT, Tan DT. Compressive C-
aging patients with TMD is recogniz- a non-inflamed, otherwise asympto- shaped lamellar keratoplasty: A surgical alternative for
ing the condition and differentiating it matic eye. the management of severe astigmatism from peripheral
corneal degeneration. Ophthalmol 2005;112(3):425-30.
from other peripheral corneal degener- • Key differential diagnoses of TMD 13. Hahn TW, Kim JH. Two-step annular tectonic lam-
ations. In questionable cases, corneal include the following: ellar keratoplasty in severe Terrien’s marginal degenera-
topography can be a helpful diagnostic • Peripheral corneal melting (kera- tion. Ophthalmic Surg 1993;24(12):831-4.
14. Chen L, Chen J, Yang B, et al. A preliminary report
technique, demonstrating corneal flat- tolysis) secondary to collagen vascular of epikeratophakia for the treatment of Terrien’s degen-
tening at the juncture of the furrow and disease (e.g., rheumatoid arthritis or eration. Yan Ke Xue Bao 1997;13(2):79-81.
CHEMICAL/TOXIC KERATO- termed punctate epitheliopathy and fibrosis in 66% of cases, severe inflam-
CONJUNCTIVITIS exactly resembles its description (dif- mation in 21% of cases, giant cell reac-
fuse, dot-like compromise either con- tion in 28% of cases and stromal calci-
Signs and Symptoms fined to the area of contact or distrib- fication in 14% of cases.7 Further,
Toxic keratoconjunctivitis, some- uted equally throughout the entire goblet cell absence was associated with
times referred to as chemical keratitis or tissue). The conjunctivae, while inject- squamous metaplasia of the conjunctiva
toxic follicular conjunctivitis, results ed, will appear elevated, boggy and and associated with long duration of
when the cornea, palpebral and bulbar insult, indicating that chemical
conjunctiva and surrounding tissue are injuries may produce lasting
exposed to any number or combinations effects, even after the event has
of foreign substances.1-4 The process passed.7
may occur unilaterally or bilaterally. The immune system has two
Symptoms occurring from chronic divisions, each containing several
exposure include ocular itching, burn- components. The cellular immune
ing and tearing, corneal punctate system has a cellular component
epitheliopathy, injection of the bulbar (leukocytes and other supportive
and palpebral conjunctivae, chemosis of cells) and a humoral component
the conjunctiva and adnexa and inferior (antibodies).13 The system relies
and/or superior conjunctival follicles primarily on the cellular system to
Chemical keratitis: note the “ground glass” appearance
and papillae in the absence of lym- of the cornea. recognize foreign substances and
phadenopathy.1-4 If the reaction is sub- initiate the first attack.13,14 The
stantial, involves a large area or the chemotic without being firm, warm or components of the cellular system
exposure is diffuse, an anterior chamber painful to the touch. In some instances, include granulocytes (neutrophils,
reaction is possible. The severity of the the term “watch glass” is employed basophils, eosinophils) and macro-
external damage and internal inflam- because the domed appearance of the phages (which phagocytize antigen and
mation depends upon the nature of the conjunctiva, as it is juxtaposed against present it to T-cells). It also includes T-
offending substance (caustic, bland, the cornea, resembles the way a watch’s helper lymphocytes, which recognize
acid, base, solid, liquid, gas or light) crystal interfaces with its casing. foreign proteins presented by macro-
along with the duration (long time vs. Likewise, the skin and adnexa may be phages and bind to them, causing the
short time) and type of contact (direct involved, with a response ranging from release of lymphokines and alerting
or indirect).5 It is important to recall itching to full-blown urticaria or boggy other lymphocytes to the presence of
that phototoxicity (exposure to ultravi- edema. foreign antigens and cytotoxic T-cells
olet light, typically from a welder’s arc that destroy abnormal host cells.
or sunlight reflected by snow) is a ker- Pathophysiology Suppressor T-cells also play a role by
atitis-producing source.4,6 When expo- The toxic/allergic response is classi- suppressing the immune response. B
sure to an agent or combination of sub- cally considered an overreaction of the cells differentiate into plasma cells,
stances or irritants (mechanical body’s immune system to immunogens producing antibodies against foreign
included) continues without treatment or allergens.7-13 The reaction can be invaders. An antibody is a complex gly-
or antidote, a fibrovascular adaptation innate or acquired. This overaction is coprotein produced by plasma cells that
of the conjunctival tissue may ensue.7 manifested when the body responds are highly specific for the antigen that
This finding is known as pannus.7 hyperactively to any exogenous materi- stimulated their production. Mast cells
Typically, patients present in one of al. The chemical may be overtly are also included as members of the
two ways: either they report with an destructive (such as gasoline, ammonia cellular immune team.13,14
unexplained red eye, oblivious to a or chlorine) or may be a topical medi- Notwithstanding the other elements
causative vector, or they report that cine, a contact lens, contact lens solu- of the response, the key component to
their eye was accidentally exposed to tion, dust or dander.1-13 The resultant the ocular allergic response is the mast
something noxious. In the case of the tissue response is generated by the cell. When mast cells interact with spe-
phenomenon known as medicamen- release of cytokines and chemoattrac- cific allergens, it is like a lock being
tosa, there will be a history of starting a tants. When researchers analyzed the opened by a key. They open (degranu-
new ocular medication, preparation tissue response that produces pannus late), discharging chemical substances
(i.e., contact lens solution, rewetting following chemical injury, they found called mediators into the surrounding
drop) or contact lens.8 Diagnosis is typ- that the tissue contained epithelial tissues.11 The primary chemical media-
ically straightforward. The keratitis is hyperplasia in 62% of cases, active tors include histamine (responsible for
increased vascular permeability, vasodi- bral conjunctival epithelium infiltrated dote for the exposure is irrigation. This
latation, bronchial constriction and by lymphocytes and plasma cells.13,15 information should be on the product
increased secretion of mucous), neutral The keratitis that occurs may be sec- label or material safety data sheet
CORNEA
proteases (which generate other inflam- ondary to the agent itself or may be (MSDS). The procedure for self-lavage
matory mediators) and arachidonic acid cytokine expression. Absorption of is to run water from a tap or nozzle into
(a crucial component of the cyclooxyge- excessive amounts of ultraviolet light cupped hands, placing the eye into the
nase pathway leading to production of (UVA, UVB) can overwhelm the corneal formed receptacle. Copious blinking
prostaglandins and leukotrienes).15 endothelial pump, inducing corneal enables the rinse.5,16 In the office, irriga-
Pathophysiologically, there are four edema with all its concomitant signs and tion can be augmented manually by
types of hypersensitivity reactions.13 symptoms.4 using a sterile ophthalmic saline applied
Type I reactions are immediate hyper- Another type of corneal toxic/allergic forcefully and directly to all surfaces or
sensitivity or anaphylactic reactions. reaction has recently been reported.8 by flushing the eye with a sterile intra-
They produce sudden mass degranula- Researchers have discovered a potential venous saline solution run through a
tion of mast cells mediated by the anti- long-term inflammatory upregulation Morgan lens apparatus.5,16
body IgE.13 Type II reactions are classi- within the cornea and conjunctiva sec- Following any necessary first aid,
fied as autoimmune and involve a ondary to the preservative benzalkonium cold compresses, artificial tears and
body’s impaired ability to distinguish chloride.8 It has been postulated that ointments can soothe and lubricate the
self from non-self.13 Abnormalities in other preservatives may also produce this conjunctiva, skin and cornea as needed.
this element of the system give rise to response. In a report outlining two com- Topical decongestants (naphazoline,
diseases in which auto-antibodies are bined studies, histopathological effects phenylephrine, and so on, b.i.d.–q.i.d.)
produced and directed against the of antiglaucoma drugs on the conjuncti- produce vasconstriction, which reduces
host.13 Type III reactions involve com- va and trabecular meshwork demon- hyperemia, chemosis and other symp-
bined formations of antigen and anti- strated toxic/immunoinflammatory toms by retarding the release of the
body known as immune complexes.13 effects on both tissues.8 This data sup- chemical mediators into the tissues
Offending triggers may be intrinsic ports other findings, and together they from the bloodstream. Topical antihist-
(e.g., a protein molecule) or extrinsic (a illuminate a mechanism by which surgi- amines along with antihistamine/mast-
penicillin molecule) producing a signif- cal glaucoma treatment (trabeculectomy) cell stabilizing combinations (Pataday,
icant tissue response.13 Type IV reac- may fail in young patients. Evidence has Patanol, Zaditor, Optivar) and oral
tions, sometimes referred to as cell- been gathered citing the upregulated antihistamines (Benadryl, 25–50 mg,
mediated hypersensitivity reactions, inflammatory processes, created by plac- p.o., t.i.d.) are also excellent therapies
involve the T lymphocytes and lym- ing some individuals on these prepara- for acute signs and symptoms.15 The
phokines.13 The reaction is classically tions for a long period, as inducing nonsteroidal anti-inflammatory drugs
delayed until a sufficient volume of increased, aggressive healing that renders (NSAIDS; Acular, Voltaren, Xibrom,
antigens stimulate the chemical cas- some of the surgical corrective proce- Nevanac b.i.d.–q.i.d.) may offer signifi-
cade.13 Here, the individual has the dures ineffective.8 cant pain relief in moderate cases, with
potential to respond when the appro- topical steroidal preparations (Alrex,
priate levels of antigen become present. Management Lotemax, Pred Mild and Forte,
This may take one exposure or 100 Since there are many strata of ocular Inflammase Mild and Forte, FML and
exposures. Classically, following the allergic reactions, management is pri- FML Forte suspensions b.id.–q.i.d.)
response, which is rarely life-threaten- marily aimed at eliminating the reserved for the most severe presenta-
ing, the patient is bewildered, recogniz- causative substance and reducing symp- tions.1-15 In instances in which the
ing that he or she had been engaged tomatology.1-17 In the event of an acute cornea is sufficiently tattered, topical
with that substance a number of times injury, lavage should be completed with antibiotic coverage may be prudent.
without any complication whatsoever. single and double lid eversion. If Bandage contact lenses and cycloplegia
The Type I and IV reactions govern patients call to report that they have can also be included as needed.17
toxic/allergic keratoconjunctival disease. been involved in an accidental chemical Finally, oral analgesics such as aspirin or
In the ocular tissues, the result of exposure, they should be advised to ibuprofen can be used to settle excessive
these chemical exchanges appear as copiously lavage immediately before discomfort and referred pain.17 If
conjunctival and adnexal vasodilation, coming to the office. Patients who corneal edema is significant, topical
producing chemosis and edema.12,14 require over-the-phone first aid should hypertonic drops and ointments can be
Conjunctival follicles are hyperplasia of be advised to brush off all powdered used q.d.–q.i.d. to restore normal levels
lymphoid tissue within the eyelid stro- chemicals before attempting lavage and of hydration.
ma and papillae are hyperplastic palpe- to make sure the recommended anti-
corneal scrapings for microbiologic resistance were encountered more com- and every two hours at night. For days
studies. The standard of care supports monly in the fluoroquinolone group, 4 and 5, one drop every two hours by
culturing most, if not all, suspected caution should be exercised in using flu- day and every four hours at night, and
CORNEA
infectious ulcers using a platinum oroquinolones in large, deep ulcers in for days 6 and 7, one drop every four
spatula with plating directly onto elderly patients.7,8 hours. After day 7, the antibiotic was
blood and chocolate agar medium. Despite clear efficacy of fluoro- tapered to every six hours and stopped
quinolones in managing bacterial when appropriate.21
keratitis, consideration must be Although fourth-generation fluoro-
given to the increasing resistance to quinolones have assisted greatly in
these drugs.4,9-11 Since their incep- managing bacterial keratitis, it must be
tion, there has been a rise in the inci- noted that they are not without fail.
dence of bacterial isolates in keratitis There are now reports of patients
Bacterial keratitis with mucopurulent discharge. that exhibit resistance to the early- developing resistance to these medica-
generation fluoroquinolones, espe- tions.24,25 Recently approved by the
Certainly, culturing is mandated when cially among the Gram-positive organ- FDA is a higher-dose formulation of
the infiltrate is in the visual axis, if the isms.4,5,12-15 Even cephazolin, commonly levofloxacin, 1.5% (Iquix), for treating
depth of the infiltrate approaches 25% employed in fortified form, has seen bacterial keratitis. This formulation is
or 50% of the corneal thickness, if increasing bacterial resistance.14 the highest concentration available for
there is scleral extention, if the infil- One method of combating the any ocular antibiotic.26
trate is not responding in a seemingly increasing problem of fluoroquinolone Strong cycloplegia is also recom-
appropriate fashion to therapy, or if resistance and rising level of Gram-pos- mended, in the form of homatropine
the infiltrate occurs in an immuno- itive infections are the fourth-generation 5% or scopolamine 0.25% b.i.d.. If this
compromised or hospitalized patient. topical fluoroquinolones. Two fourth- is insufficient, then atropine 1% b.i.d.
Additionally if a rare infection is sus- generation fluoroquinolones—moxi- is indicated. Adjunctive use of cold
pected or atypical infiltrate is seen, floxacin (Vigamox, Alcon) and gati- compresses will also help to reduce
cultures are also mandated. An alter- floxacin (Zymar, Allergan)—have a inflammation.
native for culturing of less-threatening greatly lowered resistance rate, while The patient should be followed
keratitis involves a mini-tip calcium providing much greater Gram-positive daily until the infection is well under
alginate culturette and transport- activity than previous-generation fluoro- control. If the results of cultures and
media–containing carrier. However, quinolones.15-21 Gatifloxacin was shown sensitivities show that the initially pre-
the effectiveness of the fluoro- to have a significantly better action s c r i b e d
quinolone antibiotics has led many against Gram-positive cocci both in antibiotic is
practitioners away from this standard. vitro and in vivo compared with appropriate
Microbiologic identification is most ciprofloxacin.22 for the infec-
crucial for central lesions that threaten Another study examining the efficacy tive organ-
vision, cases in which perforation is a of moxifloxacin compared with standard ism, or if the
risk, and in institutionalized patients therapies in patients with bacterial ker- Bacterial keratitis. p a t i e n t
in nursing homes and hospitals where atitis reported no difference in healing shows signs
methicillin-resistant S. aureus (MRSA) rate, cure rate or complications between of clinical improvement (the ulcer does
infections are possible.6 fortified cep- not worsen and pain and photophobia
Empirical broad-spectrum antibiotic hazolin and are reduced) at the 24–48 hour follow-
therapy must be initiated prior to tobramycin, up visit, a topical corticosteroid, such as
obtaining culture results. Monotherapy ofloxacin or prednisolone acetate 1% or loteprednol
with fluoroquinolone eye drops was moxifloxacin, etabonate 0.5% q.i.d.-q2h can be
shown in one report to result in shorter although it added with caution to speed resolution
duration of intensive therapy and short- must be noted and decrease corneal scarring.
Bacterial keratitis with
er hospital stay compared to that of hypopyon. that the con- Although steroids have historically
combined fortified therapy (tobramycin- centration of been avoided in managing infectious
cefazolin). This finding may have result- moxifloxacin used in this study was keratitis, judicious use can be benefi-
ed from quicker clinical response of double that available commercially.23 In cial. Antibiotics can suppress the infec-
healing as a result of less toxicity in the this study, moxifloxacin was instilled tive organism, and corticosteroids can
patients treated with fluoroquinolones. every hour, day and night, for 48 hours, inhibit the corneotoxic inflammatory
However, as some poor outcomes due to and on the third day, every hour by day response. It has been feared that the
immunosuppressive effects of steroids reduces beneficial effects. A cautionary activity of fluoroquinolones against ocular bacterial iso-
lates in São Paulo, Brazil. Cornea 2007;26(2):194-8
could enhance bacterial replication note: Be comfortable that the antibiot- 18. Duggirala A, Joseph J, Sharma S, et al. Activity of
and worsen infection. However, if the ic has sterilized the ulcer before insti- newer fluoroquinolones against Gram-positive and
chosen antibiotic is effective against tuting the steroid. Gram-negative bacteria isolated from ocular infections:
an in vitro comparison. Indian J Ophthalmol
the organism, the concurrent use of • Oral doxycycline and high-dose 2007;55(1):15-9.
steroids will not inhibit the bacterici- vitamin C may reduce stromal damage 19. Caballero AR, Marquart ME, O’Callaghan RJ, et al.
dal effect of the antibiotic.27-33 in conditions such as bacterial keratitis. Effectiveness of fluoroquinolones against Mycobacterium
abscessus in vivo. Curr Eye Res 2006;31(1):23-9.
Steroids should not be employed 20. Lee SB, Oliver KM, Strube YN, et al. Fourth-gener-
1. Green M, Apel A, Stapleton F. Risk factors and
until the antibiotic has been given causative organisms in microbial keratitis. Cornea ation fluoroquinolones in the treatment of mycobacteri-
enough time to sterilize the ulcer. A 2008;27(1):22-7. al infectious keratitis after laser-assisted in situ ker-
2. Keay L, Edwards K, Naduvilath T, et al. Microbial atomileusis surgery. Can J Ophthalmol 2005;40(6):
minimum 24-hour loading period is 750-3.
keratitis predisposing factors and morbidity.
recommended. One must also be cer- Ophthalmol 2006;113(1):109-16. 21. Callegan MC, Ramirez R, Kane ST, et al.
tain that the infection observed is not 3. Bourcier T, Thomas F, Borderie V, et al.. Bacterial Antibacterial activity of the fourth-generation fluoro-
keratitis: predisposing factors, clinical and microbiolog- quinolones gatifloxacin and moxifloxacin against ocular
of herpetic viral, fungal or protozoan pathogens. Adv Ther 2003;20(5):246-52.
ical review of 300 cases. Br J Ophthalmol
origin before initiating topical steroids. 2003;87(7):834-8. 22. Parmar P, Salman A, Kalavathy CM, et al.
Steroids should be used only in con- 4. Schaefer F, Bruttin O, Zografos L, et al. Bacterial Comparison of topical gatifloxacin 0.3% and cipro-
keratitis: A prospective clinical and microbiological floxacin 0.3% for the treatment of bacterial keratitis. Am
junction with true bactericidal antibi- J Ophthalmol 2006;141(2):282-286.
study. Br J Ophthalmol 2001;85(7):842-7.
otics, such as fluoroquinolones or forti- 5. Alexandrakis G, Alfonso EC, Miller D. Shifting trends 23. Constantinou M, Daniell M, Snibson GR, et al.
fied antibiotics. A recent report noted in bacterial keratitis in south Florida and emerging Clinical efficacy of moxifloxacin in the treatment of bac-
resistance to fluoroquinolones. Ophthalmol terial keratitis: A randomized clinical trial. Ophthalmol
improved visual outcomes for eyes with 2007;114(9):1622-9.
2000;107(8):1497-502.
bacterial keratitis from 1995–2005, 6. Sotozono C, Inagaki K, Fujita A, et al. Methicillin- 24. Moshirfar M, Meyer JJ, Espandar L. Fourth-gener-
commensurate with increased use of resistant Staphylococcus aureus and methicillin-resist- ation fluoroquinolone-resistant mycobacterial keratitis
ant Staphylococcus epidermidis infections in the after laser in situ keratomileusis. J Cataract Refract
topical corticosteroids in conjunction Surg 2007;33(11):1978-81.
cornea. Cornea 2002;21(7 Suppl):S94-S101.
with topical antibiotics. The authors 7. Gangopadhyay N, Daniell M, Weih L, et al. 25. Jhanji V, Sharma N, Satpathy G, et al. Fourth-gen-
speculated that increased emphasis on Fluoroquinolone and fortified antibiotics for treating eration fluoroquinolone-resistant bacterial keratitis. J
bacterial corneal ulcers. Br J Ophthalmol Cataract Refract Surg 2007;33(8):1488-9.
management of inflammation in con- 26. McDonald MB. Research review and update:
2000;84(4):378-84.
junction with the infectious process 8. Prajna NV, George C, Selvaraj S, et al. Bacteriologic IQUIX (levofloxacin 1.5%). Int Ophthalmol Clin 2006;
may have contributed to the improved and clinical efficacy of ofloxacin 0.3% versus 46(4):47-60.
ciprofloxacin 0.3% ophthalmic solutions in the treat- 27. Engel LS, Callegan MC, Hobden JA, et al.
outcomes.34 Effectiveness of specific antibiotic/steroid combinations
ment of patients with culture-positive bacterial keratitis.
Cornea 2001;20(2):175-8. for therapy of experimental Pseudomonas aeruginosa
Clinical Pearls 9. Wilhelmus KR, Abshire RL, Schlech BA. Influence of keratitis. Curr Eye Res 1995;14(3):229-34.
fluoroquinolone susceptibility on the therapeutic 28. Hobden JA, Hill JM, Engel LS, et al. Age and ther-
• If a patient presents with a corneal apeutic outcome of experimental Pseudomonas aerug-
response of fluoroquinolone-treated bacterial keratitis.
infiltrate without overlying epithelial Arch Ophthalmol 2003;121(9):1229-33. inosa keratitis treated with ciprofloxacin, prednisolone,
staining, then the condition is likely 10. Parmar P, Salman A, Kalavathy CM, et al. and flurbiprofen. Antimicrob Agents Chemother
Pneumococcal keratitis: a clinical profile. Clin Exper 1993;37(9):1856-9.
not infectious bacterial keratitis. 29. Hobden JA, Engel LS, Hill JM, et al. Prednisolone
Ophthalmol 2003;31(1):44-7.
• Using strong bactericidal antibi- 11. Goldstein MH, Kowalski RP, Gordon YJ. Emerging acetate or prednisolone phosphate concurrently admin-
otics will eliminate the infective organ- fluoroquinolone resistance in bacterial keratitis: A 5-year istered with ciprofloxacin for the therapy of experimen-
review. Ophthalmol 1999;106(7):1313-8. tal Pseudomonas aeruginosa keratitis. Curr Eye Res
isms and sterilize the ulcer, but it will 1993;12(5):469-73.
12. Afshari NA, Ma JJ, Duncan SM, et al. Trends in
do nothing to quell the inflammatory resistance to ciprofloxacin, cefazolin, and gentamicin in 30. Hobden JA, O’Callaghan RJ, Hill JM, et al.
reaction. In such instances, the inflam- the treatment of bacterial keratitis. J Ocul Pharmacol Ciprofloxacin and prednisolone therapy for experimen-
Ther 2008;24(2):217-23. tal Pseudomonas keratitis. Curr Eye Res
matory reaction is as damaging to the 1992;11(3):259-65.
13. Sharma V, Sharma S, Garg P, et al Clinical resist-
cornea as is the infective organism. If ance of Staphylococcus keratitis to ciprofloxacin 31. Carmichael TR, Gelfand Y, Welsh NH. Topical
evidence exists that the antibiotic is monotherapy. Indian J Ophthalmol 2004;52(4):287-92. steroids in the treatment of central and paracentral
14. Leibovitch I, Lai TF, Senarath L, et al. Infectious corneal ulcers. Br J Ophthalmol 1990;74(9):528-31.
suppressing the infective organism, 32. Wilhelmus KR. Indecision about corticosteroids for
keratitis in South Australia: Emerging resistance to cep-
then corticosteroid use will inhibit the hazolin. Eur J Ophthalmol 2005;15(1):23-6. bacterial keratitis: An evidence-based update.
inflammatory reaction and speed heal- 15. Kowalski RP, Dhaliwal DK, Karenchak LM, et al. Ophthalmol 2002;109(5):835-42.
Gatifloxacin and moxifloxacin: An in vitro susceptibility 33. Stern GA, Buttross M. Use of corticosteroids in
ing and reduce corneal scarring. combination with antimicrobial drugs in the treatment of
comparison to levofloxacin, ciprofloxacin, and ofloxacin
• For steroids to be most beneficial, using bacterial keratitis isolates. Am J Ophthalmol infectious corneal disease. Ophthalmol. 1991;98(6):
prescribe them while the ulcer bed is 2003;136(3):500-5. 847-53.
16. Mather R, Karenchak LM, Romanowski EG, et al. 34. Al-Shehri A, Jastaneiah S, Wagoner MD. Changing
still open, usually within the first trends in the clinical course and outcome of bacterial
Fourth generation fluoroquinolones: New weapons in
24–48 hours after you initiate antibiot- the arsenal of ophthalmic antibiotics. Am J Ophthalmol keratitis at King Khaled Eye Specialist Hospital. Int
ic therapy. Waiting until the ulcer re- 2002;133(4):463-6. Ophthalmol 2008;Apr 3 [Epub ahead of print].
epithelializes before adding a steroid 17. Oliveira AD, D’Azevedo PA, Francisco W. In vitro
Although secondary glaucoma is com- placement in each case is characteristic the lens into the anterior chamber can
monly associated with crystalline lens but by no means completely diagnostic. also result in a reverse pupil block angle-
subluxation, the cause is not always pupil Marfan’s syndrome is the most common- closure glaucoma.27
block; open-angle glaucoma can occur as ly encountered underlying condition in
well, presumably from lens-induced patients with crystalline lens subluxation. Management
inflammation.10 More than 70% of patients with Marfan’s Extraction of a dislocated lens can
Biomicroscopically, there will be a syndrome have displacement of the crys- prove to be difficult. For that reason, lens
displaced crystalline lens. This appears as talline lens.23 In Marfan’s syndrome, the subluxation alone is not sufficient to
a black crescent at the edge of the lens lens tends to be displaced superior tem- mandate surgery.9 It is recommended
against a red reflex from the fundus. The porally. This results from a predominance that, in the absence of pupil block glau-
lens can be dislocated up and out, down of abnormally constructed collagen vas- coma, corneal decompensation, inflam-
and in, down and out, nasally or tempo- cular tissue and faulty lens zonules and is mation or intractable visual disability, a
rally, or completely displaced into the typically non-progressive. Further, as the subluxed lens should be left alone in
posterior or anterior chamber. There zonules are still attached to the lens, favor of less invasive options.9 For
may also be phacodonesis (tremulous- some degree of accommodation exists. induced refractive errors that are stable,
ness of the lens due to loss of zonular Homocystinuria, a defect in amino visual correction with glasses or contact
support) and iridodonesis (tremulous- acid metabolism, results in brittle zonules lenses should be investigated.
ness of the iris).13 that rupture.5,13 This allows the lens to If the lens dislocates into the posterior
displace inferior nasally or even into the chamber but the posterior capsule remains
Pathophysiology anterior chamber. There is no accommo- intact and no inflammation is induced, it
Subluxation implies displacement of dation in this case and the condition may can be monitored.9 However, if inflamma-
the crystalline lens. Luxation refers to a 5,13
be progressive. Two other conditions tion that cannot be managed topically is
lens that is totally dislocated. The term that should be mentioned are simple induced or retinal damage is threatened,
ectopia lentis has been used interchange- ectopia lentis and ectopia lentis et pupillae. then vitrectomy and lens extraction are
ably with subluxation. Simple ectopia lentis is an necessary. Late onset inflammation is
However, this should be a autosomal dominant con- always possible. Patients require life-long,
term reserved for bilateral dition in which the lenses timely and periodic observation.9
cases. Subluxation of the are dislocated superotem- In cases where there is suspected loss
crystalline lens has been porally, but there are no of zonular adherence (often with hyper-
described as being either other associated systemic mature cataracts) with subsequent risk of
acquired or congenital. abnormalities. Ectopia dislocation into the anterior chamber,
Better terminology would Crystalline lens subluxation. lentis et pupillae is likewise pharmacological dilation should be
be that subluxation of the an isolated inherited condi- avoided until surgical consultation can
lens can be either acquired (such as from tion, albeit autosomal recessive, in which be obtained. In cases where the lens has
trauma) or due to congenital systemic the lenses are displaced temporally in already dislocated into the anterior
causes. Rarely are infants born with dis- opposing directions.24-26 chamber, the patient can be reclined and
placed lenses; instead the phenomenon The main concern with dilated, to attempt reposi-
develops during life due to a predispos- lens subluxation is the tioning by carefully manip-
ing systemic condition.22 development of secondary ulating the head until the
Traumatic subluxation is slightly angle-closure glaucoma. lens falls back into place.
more common than lens displacement Any time the crystalline Following this, pilocarpine
associated with underlying systemic dis- lens displaces, the possibili- solution can be instilled to
orders.12 Traumatic mechanical stretch- ty exists that the lens can stabilize the structure, and
ing of the zonules is the cause of the sub- come into firm apposition Crystalline lens subluxation a surgical consultation can
luxation. This occurs as the eye is with the back surface of the as seen on funduscopy. be obtained.
compressed in an anterior-posterior iris. When the pupil is In cases in which pupil
direction (such as with impact by a fist or obstructed, there is pupil block, iris block angle-closure glaucoma develops,
other projectile) and the subsequent dis- bombé and secondary angle closure.19-21 laser peripheral iridotomy should be per-
tention of the globe in the medial-later- Should a lens completely dislocate into formed as soon as possible. However, this
al plane ruptures the zonular fibers. the anterior chamber, concern must be rarely manages the condition successful-
Spontaneous lens subluxation associ- for the lens touching the cornea, irre- ly. Patients frequently require lens extrac-
ated with congenital conditions varies in versibly damaging the endothelial cells tion with intraocular lens implantation.
pathophysiologic mechanism depending with subsequent chronic corneal edema Phacoemulsification with posterior
upon the condition. The direction of dis- and decompensation.13 Displacement of chamber intraocular lens and capsular
greater statistical risk for the develop- has several options. Microsurgical repair prostaglandins (a mediator of the
ment of late glaucoma.11 using a 22.0-mm plastic-handled 27- immune response), so they may worsen
gauge straight needle through a 1.0-mm inflammation. Also, they take too long
Management distal hole can serve as a passage for 9–0 to reach a therapeutic effect.
Because iridodialysis involves the or 10–0 mm polypropylene or nylon • The D-shaped pupil caused by iri-
traumatic (injurious or surgical) dissec- sutures.13 Alternately, a sutureless tech- dodialysis should not be confused with
tion of well-vascularized and innervated nique (for the repair itself ) involves a the “peaked” or “pointed” pupil found in
iris tissue, an accompanying secondary limbal peritomy, multiple sclerostomies penetrating injuries.
iridocyclitis and hyphema should be to gain access to the iris base at multiple • Following a severe injury with sub-
anticipated during the acute phase of clock hours of the iridodialysis (using a stantial peripheral iris release, the structure
the trauma.12 In such cases, microvitreoretinal blade) may appear floppy or tremulous as the eye
topical cycloplegics such as and placement with incar- moves. This is known as iridodonesis. If
atropine 1% q.d.–t.i.d. can ceration of the peripheral the zonules are involved and the lens
provide pain relief by miti- iris through these ports appears unstable as the eye moves, the
gating the spasmodic using a vitreoretinal for- phenomenon is known as phacodonesis.
response both of the iris ceps with conjunctival clo- • Iris coloboma is the result of an
and ciliary body, while the sure using absorbable arrested developmental syndrome asso-
aggressive use of topical Partial iridodialysis. sutures can be performed.13 ciated with the PAX6 gene. Here, por-
steroidal and nonsteroidal The latter technique is tions or entire sectors of the iris may be
anti-inflammatory preparations can be suitable for use in simple iridodialysis missing, with or without affecting
employed to reduce the incited immune repair in conjunction with other intraoc- pupil shape. However, the patient will
response. In the event that IOP ular procedures.14 Surgical repair of this provide a history of having had that
becomes acutely raised secondary to defect since birth.
obstruction of the trabecular meshwork
1. Oyster CW. The iris and pupil. In: Oyster CW. The
by blood or inflammatory debris, topical Human Eye: Structure and Function. Sunderland, MA:
brimonidine, beta-blocker or carbonic Sinauer Assoc., Inc., 1999, pp. 411-46.
anhydrase therapy can be used until the 2. Lehto KS, Sulander PO, Tervo TM. Do motor vehicle
airbags increase risk of ocular injuries in adults?
injury is healed. Ophthalmol 2003;110(6):1082-8.
Because the consequence of angle 3. García-Medina JJ, García-Medina M, Pinazo-Durán
MD. Severe orbitopalpebral emphysema after nose blow-
recession and of late or post-traumatic ing requiring emergency decompression. Eur J
glaucoma exists in all patients sustaining Ophthalmol 2006;16(2):339-42.
ocular blunt trauma—whether or not Complete iridodialysis. 4. Morris DS. Ocular blunt trauma: Loss of sight from an
ice hockey injury. Br J Sports Med 2006;40(3):e5.
visible damage is evident—following the 5. Vize CJ, Gauba V, Atkinson PL Eye injury as a result of
repair and recovery from all acute seque- injury is not emergent and often accom- coat toggle trauma. Eye 2007;21(1):94-5.
6. Wong MH, Yang M, Yeo KT. Elastic cord-related ocu-
lae, the entire angle in both eyes (for plished following the resolution of all lar injury. Singapore Med J 2008;49(4):e90-2.
comparison) should be inspected with resultant acute traumatic complications. 7. Oyster CW. The limbus and the anterior chamber. In:
gonioscopy.12 Patients with an ocular Oyster CW. The Human Eye: Structure and Function.
Sunderland, MA: Sinauer Assoc., Inc., 1999, pp. 379-410.
blunt-force history should be periodical- Clinical Pearls 8. Ahmad F, Kirkpatrick NA, Lyne J, et al. Buckling and
ly assessed for rising IOP to exclude a • Any trauma capable of producing hydraulic mechanisms in orbital blowout fractures: Fact or
fiction? J Craniofac Surg 2006;17(3):438-41.
delayed traumatic effect on aqueous iridodialysis is capable of producing con- 9. Ellong A, Ebana Mvogo C, Nyouma Moune E, et al.
drainage.9-12 In the event that late or trecoup posterior segment complica- Post-traumatic glaucoma with irido-corneal angle injuries
post-traumatic glaucoma develops, it can tions. In all instances, the posterior seg- in Cameroon. Bull Soc Belge Ophtalmol 2005;(298):21-8.
10. Manners T, Salmon JF, Barron A, et al.
be treated using the same algorithm as ment of both eyes should be evaluated. Trabeculectomy with mitomycin C in the treatment of
with primary open-angle glaucoma. • Since a frequent complication of post-traumatic angle recession glaucoma. Br J
Ophthalmol 2001;85(2):159-63.
Iridodialyses not requiring surgical iridodialysis is hyphema, gonioscopy at 11. Sihota R, Kumar S, Gupta V, et al. Early predictors of
repair and not producing ill cosmetic the time of acute presentation may not traumatic glaucoma after closed globe injury: Trabecular
effects require no additional ophthalmic be desirable. The procedure will not pro- pigmentation, widened angle recess, and higher baseline
intraocular pressure. Arch Ophthalmol 2008;126(7):921-6.
management. Those patients upset by vide information that improves treat- 12. Walker NJ, Foster A, Apel AJ. Traumatic expulsive iri-
the shape of their pupil or the appear- ment and may move a well-formed clot, dodialysis after small-incision sutureless cataract surgery.
J Cataract Refract Surg 2004;30(10):2223-4.
ance of the iris or suffering from any sec- promoting bleeding.
13. Bardak Y, Ozerturk Y, Durmus M, et al. Closed cham-
ondary effects of having an additional • The topical prostaglandins are not ber iridodialysis repair using a needle with a distal hole. J
iris opening may be fit with large diam- an effective choice for reducing IOP in Cataract Refract Surg 2000;26(2):173-6.
14. Richards JC, Kennedy CJ. Sutureless technique for
eter painted/opaque contact lens. In the wake of any acute injury. They are repair of traumatic iridodialysis. Ophthalmic Surg Lasers
cases requiring surgical remediation, one chemically similar to our own Imag 2006;37(6):508-10.
1. Olea Vallejo JL, Muñoz Corrales E, Mateos Poch JM, coherence tomography in asteroid hyalosis. Retina With fluorescein angiography, the
et al. Vitrectomy for asteroid hyalosis. Arch Soc Esp 2006;26(6):661-5
Oftalmol 2002;77(4):201-4 25. Browning DJ, Fraser CM. Optical coherence tomog-
aneurysm will hyperfluoresce early in
2. Parnes RE, Zakov ZN, Novak MA, et al. Vitrectomy in raphy to detect macular edema in the presence of aster- the angiogram, showing a characteristic
patients with decreased visual acuity secondary to aster- oid hyalosis. Am J Ophthalmol 2004;137(5):959-61 balloon-appearance with late-phase
oid hyalosis. Am J Ophthalmol 1998;125(5):703-4
3. Lambrou FH Jr, Sternberg P Jr, Meredith TA, et al.
leakage.5 In cases of extensive hemor-
Vitrectomy when asteroid hyalosis prevents laser photo- RETINAL ARTERIAL rhage, indocyanine green (ICG)
coagulation. Ophthalmic Surg 1989;20(2):100-2 MACROANEURYSM angiography can better identify the
4. Fawzi AA, Vo B, Kriwanek R, et al. Asteroid hyalosis
in an autopsy population: The University of California at
focal aneurysmal dilatation.10
Los Angeles (UCLA) experience. Arch Ophthalmol Signs and Symptoms Several causes of vision loss may occur
2005;123(4):486-90 Most patients developing retinal arte- from retinal arterial macroaneurysm. Of
5. Mitchell P, Wang MY, Wang JJ. Asteroid hyalosis in an
older population: The Blue Mountains Eye Study.
rial macroaneurysms (RAMs) are older, course, leakage and rupture leading to
Ophthalmic Epidemiol 2003;10(5):331-5 typically between 50 and 80 years old.1-6 macular edema, exudation and hemor-
6. Moss SE, Klein R, Klein BE. Asteroid hyalosis in a RAMs rarely occur in younger patients, rhage are the most obvious. However,
population: The Beaver Dam eye study. Am J
Ophthalmol 2001;132(1):70-5
but when they do, there is often an asso- retinal arterial macroaneurysm rupture
7. Akram A, Niazi MK, Ishaq M, et al. Frequency of dia- ciated systemic disease.7 There appears also has been strongly associated with
betics in asteroid hyalosis patients. J Ayub Med Coll to be a female the development of macular holes and
Abbottabad 2003;15(3):10-1
8. Bergren RL, Brown GC, Duker JS. Prevalence and
preponder- retinal detachment, which can leave
association of asteroid hyalosis with systemic diseases. ance.4-6 The patients with profound vision loss
Am J Ophthalmol 1991;111(3):289-93 most com- despite complete resolution of the leak-
9. Jones WL, Twamley CR. Documented acquired
asteroid hyalosis in a case of early diagnosed diabetes
mon comor- age from aneurysmal rupture.18-24
mellitus. Optom 200;72(5):315-21 bidity is sys- Additionally, retinal arterial macroa-
10. Yazar Z, Hanioglu S, Karakoç G, et al. Asteroid temic arterial neurysms have been seen in association
hyalosis. Eur J Ophthalmol 2001;11(1):57-61.
11. Kador PF, Wyman M. Asteroid hyalosis:
hypertension, with retinal telangiectasias, arterial
Retinal arterial macroaneu- occurring in emboli and retinal vein occlusion.5,25
Pathogenesis and prospects for prevention. Eye rysm with notable vascular
2008;Mar 14 [Epub ahead of print]. dilation and hemorrhage. approximate-
12. Komatsu H, Kamura Y, Ishi K, et al. Fine structure
and morphogenesis of asteroid hyalosis. Med Electron
ly 80% or Pathophysiology
Microsc 2003;36(2):112-9 more of patients.3,5,8,9 There is also an Retinal arterial macroaneurysms are
13. Adenis JP, Leboutet MJ, Loubet R. Asteroid increased incidence of cardiovascular acquired out-pouchings of the retinal
hyalopathy. Ultrastructural study of 3 cases. J Fr
Ophtalmol 1984;7(8-9):529-34
disease and arteriosclerosis.5,6 arterioles.5 These balloon-like formations
14. Streeten BW. Vitreous asteroid bodies. Ophthalmoscopically, there will be a are caused by a break in the internal elas-
Ultrastructural characteristics and composition. Arch dilatation of a major arterial branch tic lamina of the arteriole wall through
Ophthalmol 1982;100(6):969-75
15. Winkler J, Lünsdorf H. Ultrastructure and composi-
within the first three bifurcations. which serum, lipids and blood exude into
tion of asteroid bodies. Invest Ophthalmol Vis Sci Retinal arterial macroaneurysms are typ- the surrounding
2001;42(5):902-7 ically unilateral, but may be multifocal.3,5 retina.26 However, there
16. Boissonnot M, Manic H, Balayre S, et al. Role of vit-
rectomy in patients with a decrease in visual acuity sec-
In many cases of unruptured retinal arte- is no associated micro-
ondary to asteroid hyalosis. J Fr Ophtalmol rial macroaneurysms, the patient vasculopathy as typi-
2004;27(7):791-4 remains asymptomatic and the discovery cally seen in diabetic
17. Wong SC, Sampath R. Erroneous automated refrac-
tion in a case of asteroid hyalosis. J Cataract Refract
is made during a routine fundus exami- retinopathy. Aging
Surg 2002;28(9):1707-8 nation. Often, however, by the time the arterioles demonstrate
A small, almost
18. Allison KL, Price J, Odin L. Asteroid hyalosis and patient presents, significant leakage has subclinical an increase in intimal
axial length measurement using automated biometry. J
Cataract Refract Surg 1991;17(2):181-6.
occurred and the surrounding area man- RAM. collagen and replace-
19. Fuchihata M, Saito Y, Kitaguchi Y, et al. Calcification ifests exudates and extensive pre-, intra- ment of medial muscle
on the posterior surface of an implanted silicone intraoc- and/or subretinal hemorrhage. Vitreous fibers by collagen, making them less elas-
ular lens in a patient with asteroid hyalosis. Nippon
Ganka Gakkai Zasshi 2006;110(9):736-40
hemorrhage also may occur upon rup- tic. It has been postulated that this loss of
20. Werner L, Kollarits CR, Mamalis N, et al. Surface cal- ture.10-17 Occasionally, spontaneous pul- elasticity makes arterioles more suscepti-
cification of a 3-piece silicone intraocular lens in a patient sation of an unruptured aneurysm may ble to dilatation from elevated hydrostat-
with asteroid hyalosis: a clinicopathologic case report.
Ophthalmol 2005;112(3):447-52.
be noted. When there is extensive hem- ic pressure occurring in hypertension.5
21. Foot L, Werner L, Gills JP, et al. Surface calcification orrhage, it is often difficult to identify The strong association of retinal macroa-
of silicone plate intraocular lenses in patients with aster- retinal macroaneurysm as the cause. In neurysm with hypertension points to this
oid hyalosis. Am J Ophthalmol 2004;137(6):979-87.
22. Hampton GR, Nelsen PT, Hay PB. Viewing through
such cases, neovascularization is often systemic disease as a possible contributo-
the asteroids. Ophthalmol 1981;88(7):669-72 misdiagnosed as the source. ry mechanism affecting the vessel wall.
23. Win PH, Young TA. Optos Panoramic200A fluores- If the focal dilatation is not ophthal-
cein angiography for proliferative diabetic retinopathy with
asteroid hyalosis. Semin Ophthalmol 2007;22(2):67-9
moscopically apparent, fluorescein Management
24. Hwang JC, Barile GR, Schiff WM, et al. Optical angiography can illuminate the RAM. The natural course of RAM typically
involves spontaneous sclerosis and neurysm rupture as they have the greatest
Simultaneous bilateral visual loss caused by rupture of bifurcation.5,7 Bilateral involvement is appears chalk-like.4 Cholesterol emboli
retinal arterial macroaneurysms in a hypertensive patient.
Acta Ophthalmol Scand 2005;83(1):120-2.
uncommon, but there may be multiple are the most commonly encountered
27. Tachfouti S, Lezrek M, Karmane A, et al. Retinal arte- emboli within the same eye. The emboli (80% of all emboli); fibrin-platelet
rial macroaneurysm: spontaneous occlusion after rupture. can have a reflective or refractile appear- emboli represent 14% of emboli, while
In connection with a case. Bull Soc Belge Ophtalmol
2004;(294):5-11.
ance; a dull, bulky, chalky appearance; or calcific emboli account for just 6% of vis-
28. Ohno-Matsui K, Hayano M, Futagami S, et al. may appear long and white within a ves- ible retinal emboli.8
Spontaneous involution of a large retinal arterial macroa- sel.1,5,7 Over time, retinal emboli tend to Patients frequently have concurrent
neurysm. Acta Ophthalmol Scand 2000;78(1):114-7.
29. Badii G, Messmer EP. Spontaneous regression of an
dislodge and move down the vascular tree. hypertension, a history of smoking and
acquired arterial macroaneurysm of the retina. Klin One large population study found the elevated cholesterol levels. The stress on
Monatsbl Augenheilkd 1992;200(5):537-8. 10-year cumulative incidence of retinal the arteries induced by hypertension leads
30. Brown DM, Sobol WM, Folk JC, et al. Retinal arterio-
lar macroaneurysms: Long-term visual outcome. Br J
emboli was 1.5%.2 Another large popu- to reduced elasticity of the vessels.
Ophthalmol 1994;78(7):534-8. Cholesterol deposition then
31. Yang CS, Tsai DC, Lee FL, et al. Retinal arterial occurs within the vessel walls and
macroaneurysms: risk factors of poor visual outcome.
Ophthalmologica 2005;219(6):366-72.
an atheroma forms, with subse-
32. Raymond LA. Neodymium:YAG laser treatment for quent arterial narrowing.
hemorrhages under the internal limiting membrane and Turbulent blood flow over the
posterior hyaloid face in the macula. Ophthalmol.
1995;102(3):406-11
atheroma can lead to plaque
33. Iijima H, Satoh S, Tsukahara S. Nd:YAG laser pho- ulceration, which allows small
todisruption for preretinal hemorrhage due to retinal Examples of retinal emboli lodged in the arterial system. particles to break off and flow
macroaneurysm. Retina 1998;18(5):430-4.
34. Oie Y, Emi K. Surgical excision of retinal macroa-
within the bloodstream. This
neurysms with submacular hemorrhage. Jpn J lation based study found asymptomatic accounts for the majority of cholesterol
Ophthalmol 2006;50(6):550-3. retinal emboli in 1.4% of the study pop- emboli. The origin of most cholesterol
ulation. There was an increase in preva- emboli is thought to be ulcerated athero-
RETINAL EMBOLI lence associated with age, with a preva- matous plaques in the internal or com-
lence of 0.8% in persons aged younger mon carotid artery. Fibrin-platelet emboli
Signs and Symptoms than 60 years, 1.4% for those aged 60 to typically arise from a mural thrombus,
Patients observed to have retinal 69 years, 2.1% for those aged 70 to 79 and calcific emboli are thought to arise
emboli are typically elderly and often years, and 1.5% for those aged 80 years from cardiac valvular structures.4,14
have a concurrent history of hyperten- 8
or older. There is a greater prevalence in Once an embolus has broken off from
sion, diabetes, carotid artery disease, men than women.8 Another report its point of origin, it travels the arterial
peripheral vascular disease, hypercholes- noted a 3% incidence in retinal emboli in system until it encounters a vessel whose
terolemia, hyperlipidemia, smoking and an older population.9 Notably, these
atherosclerosis.1-4 The patient is often large population studies involved prima-
asymptomatic, and the plaques are often rily whites; there is a lower prevalence of
found upon routine eye exam. However, asymptomatic retinal emboli in Hispanic
the patient may have previously experi- and Asian peoples.1,10 However, the tran-
enced transient episodes of monocular sient nature of retinal emboli makes it
vision loss (amaurosis fugax).5,6 Rarely, difficult to determine the true preva-
patients will have experienced a transient lence, and most population studies likely
ischemic attack with hemiparesis, pares- underestimate the actual prevalence.
thesia, and/or aphasia. These episodic
bouts of amaurosis fugax may be quite Pathophysiology
A rarely captured view of a plaque at the optic
frequent, and may last from several sec- Retinal emboli are heterogeneous. nerve head, which can induce a central retinal
onds to several minutes. Rarely does the One type of embolus is composed of vein occlusion.
patient have any lasting visual deficits. cholesterol and typically lodges at a ves-
Frequently, patients who describe expe- sel bifurcation. These cholesterol emboli caliber is too small to allow it to flow any
riencing amaurosis fugax will not exhib- are refractile in appearance and are farther. This causes the plaque to lodge
it retinal emboli upon examination, but sometimes known as Hollenhorst within that vessel. If blood flow is signif-
may have arteriolar narrowing and plaques.11-13 Another type of embolus is icantly impaired distal to the blockage,
sheathing.5 long and dull and appears similar to then ischemia to that tissue will ensue. If
Ophthalmoscopically, an intra-arterio- toothpaste within the arteriole lumen. the embolus lodges within a retinal arte-
lar plaque will be evident. Emboli can This type of emboli is composed of fib- riole, then retinal ischemia with corre-
occur along the course of the vessel in the rin and platelet aggregates.4 The third sponding loss of vision occurs. The result
retina or at the optic disc or at a vessel type of retinal emboli is calcific and may be a retinal artery occlusion. In the
case of cholesterol emboli, however, the with symptomatic retinal emboli.6 tomatic retinal emboli.
the condition may be unknown to the oles, resulting in acute focal inner retinal Managing patients with severe hyper-
patient and the eye exam may yield the ischemia.4,5 Acute elevation in blood pres- tension and extremely elevated BP has
first clue to this potentially asympto- sure causes smooth muscle necrosis and led to an algorithm in which patients are
matic systemic disease.1 Most common- breakdown of the blood-retina barrier, classified as having either hypertensive
ly, the patient is middle-aged or older.2 resulting in retinal hemorrhages.6,16,17 emergency or hypertensive urgency.
In addition, hypertension is more com- In extreme cases, a macular exudative Patients with extremely elevated BP but
mon and severe in African Americans star and disc edema develops. The mech- no evidence of end organ damage are
than in whites.3 Patients with only anism behind this phenomenon is poorly said to have a hypertensive urgency; oral
hypertensive retinopathy and no other understood, but it may be associated with antihypertensive medications are used to
hypertensive ocular complications are a hypertension-related increase in lower BP over 24 to 48 hours by a pri-
nearly always visually asymptomatic. mary care physician. Patients with
Findings in hypertensive retinopathy extremely elevated BP and acute
include arteriolosclerosis (artery narrow- end organ damage (cardiovascu-
ing with increased arteriole light reflex, lar, cerebrovascular, or renal) are
secondary to thickening within the blood diagnosed as having hypertensive
vessel wall, arteriovenous crossing emergency and require immediate
changes with venous constriction and treatment with a titratable short-
banking, arteriolar color changes and Two examples of hypertensive retinopathy. acting IV antihypertensive
additional vessel damage with scar for- agent.19,20
mation), cotton wool spots and flame intracranial pressure and is therefore con- In that the eye is considered an “end
shaped hemorrhages within the nerve sidered true papilledema.1,3,17 organ,” the presence of retinopathy and
fiber layer. Intraretinal hemorrhages Arteriolosclerotic changes in the reti- extremely elevated BP would technically
occur less commonly. Rarely will there be nal microvasculature will persist even if be considered a hypertensive emergency.
retinal or macular edema, and then only systemic blood pressure is reduced. Some Most clinicians don’t equate retinal hem-
in the most severe cases. In advanced hypertensive retinopathy classification orrhages and cotton wool spots as a crisis
cases, there will be a macular star or cir- schemes do not include the arterioloscle- situation. However, a patient presenting
cinate pattern (ring of exudates from the rotic changes as these vessel findings can with disc edema and macular exudative
disc to the macula) and disc edema.4-7 occur in non-hypertensive people.9 The star is suffering from malignant hyper-
One study noted a greater incidence of other hypertensive retinopathy changes tension and should be considered as
hypertensive retinopathy in women and will resolve over time with the reduction being in medical crisis. This patient
40% of hypertensive patients demon- of systemic blood pressure (BP).18 Cotton needs immediate consult with a primary
strating some degree of retinopathy.8 wool spots will develop in 24–48 hours care physician and, most likely, immedi-
There may also be concomitant comor- with the elevation of BP, and will resolve in ate transport to a hospital emergency
bidities in the form of subclinical and two to 10 weeks with the lowering of BP.4,5 room. It must be reiterated, though, that
clinical stroke, cognitive impairment, there are many causes of papilledema.
renal dysfunction and cardiovascular Management Other causes, such as an intracranial
mortality.9-13 Severe and atypical cases of Management of hypertensive retinopa- mass lesion, must also be considered in
hypertensive retinopathy have been asso- thy involves appropriate treatment of the the patient with hypertension. However,
ciated with pheochromocytoma.14,15 underlying hypertension. A large popula- in a case in which BP is extremely elevat-
tion study indicated that pharmacologic ed (e.g., 250/150mm Hg) and there is
Pathophysiology BP reduction resulted in a lower incidence disc edema with a macular star, malig-
The findings in hypertensive retinopa- of retinopathy.18 Medical co-management nant hypertension is the likely cause.
thy all stem from hypertension-induced with the primary physician is paramount.
changes to the retinal microvasculature. The ophthalmic examination may be the Clinical Pearls
Hypertension leads to a lying down of first time that a patient is discovered to • For cotton wool spots to develop
cholesterol into the tunica intima of have retinopathic changes consistent from hypertension, autoregulatory mech-
medium and large arteries. This leads to with hypertension. In that patients anisms must first be overcome. The
an overall reduction in the lumen size of demonstrating hypertensive retinopathy patient must have at least some chronic
these vessels. Arteriolosclerosis leads to also have a greater risk of subclinical and readings of 110mm Hg diastolic or high.
focal closure of the retinal microvascula- clinical stroke, cognitive impairment, • Fluorescein angiography is not
ture. This gives rise to microinfarcts (cot- renal dysfunction and cardiovascular indicated in cases of hypertensive
ton wool spots) and superficial hemor- mortality, independent of blood pressure retinopathy, since it will yield little diag-
rhages. Cotton wool spots represent levels and control, referral for additional nostic information.
occlusions of the terminal retinal arteri- evaluation may be appropriate.9-13 • Hypertensive retinopathy presents
with a “dry” retina (i.e., few hemorrhages, layers—may be seen within the affected
have been observed to display diffuse 21 years showed deterioration of vision 2. Gass JD, Oyakawa RT. Idiopathic juxtafoveolar retinal
telangiectasis. Arch Ophthalmol 1982;100(5):769-80.
pericyte degeneration, as their lumens in more than 84% of eyes, either due to 3. Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal
become occluded by abnormal basement intraretinal edema and serous retinal telangiectasis. Update of classification and follow-up
membrane material.8 These findings are detachment (Type 1) or pigmented RPE study. Ophthalmol 1993;100(10):1536-46.
4. Yannuzzi LA, Bardal AM, Freund KB, et al. Idiopathic
very similar to those seen in diabetic scar formation or CNV (Type 2).11 macular telangiectasia. Arch Ophthalmol. 2006;124(4):
retinopathy, although there is no estab- Historically, laser photocoagulation has 450-60.
lished link between IJRT and diabetes.9 been the recommended treatment early 5. Moisseiev J, Lewis H, Bartov E, et al. Superficial retinal
refractile deposits in juxtafoveal telangiectasis. Am J
In recent years, optical coherence in the course of Type I IJRT to help sus- Ophthalmol 1990;109(5):604-5.
tomography has been helpful in identi- pend the exudative process and diminish 6. Wu J, Ferrucci S. Idiopathic juxtafoveal retinal telang-
fying more detailed fundus morphology macular edema.2,3 In contrast, laser ther- iectasia. Optom 2008;79(11):653-62.
7. Tasca J, Grogg JA. Idiopathic juxtafoveolar retinal
associated with IJRT. One such finding apy is not considered a viable treatment telangiectasia: a review and case report. Clin Eye Vis Care
is that there is often progressive foveal option for Type 2 IJRT, unless frank 2000;12(1-2):79-87.
atrophy through the late stages of this neovascularization is evident on fluores- 8. Green WR, Quigley HA, de la Cruz Z, Cohen B.
Parafoveal retinal telangiectasis: light and electron
disease.10 It is thought that this collec- cein angiography.2,3,12 In fact, laser thera- microscopy studies. Retina 2005;25(5 Suppl):S162-
tive loss of retinal cells may induce py may actually enhance vessel ectasia S170.
intraretinal neovascularization and, and promote intraretinal fibrosis in these 9. Millay RH, Klein ML, Handelman IL, et al. Abnormal
glucose metabolism and parafoveal telangiectasia. Am J
ultimately, subretinal or choroidal neo- individuals.12 Ophthalmol 198;102(3):363-70.
vascularization (CNV). However, it Today, additional therapies include 10. Paunescu LA, Ko TH, Duker JS, et al. Idiopathic
should be noted that not all patients surgical removal of CNV, photodynamic juxtafoveal retinal telangiectasis: New findings by ultra-
high-resolution optical coherence tomography.
will develop CNV, as IJRT often spon- therapy with verteporfin and treatment Ophthalmol 2006;113(1):48-57.
taneously arrests.11 with anti-VEGF drugs such as beva- 11. Watzke RC, Klein ML, Folk JC, et al. Long-term
cizumab.14-16 However, these treatment juxtafoveal retinal telangiectasia. Retina 2005;25(6):727-35.
Management modalities should be considered only in 12. Park DW, Schatz H, McDonald R, Johnson RN. Grid
laser photocoagulation for macular edema in bilateral
The most crucial aspect of managing cases of marked and rapid vision loss juxtafoveal telangiectasis. Ophthalmol 1997;104(11):
patients with IJRT is recognition of the secondary to macular edema or CNV. 1838-46.
13. Berger AS, McCuen BW, Brown GC, et al. Surgical
clinical signs. This condition is relatively Otherwise, a conservative approach is rec- removal of subfoveal neovascularization in idiopathic
uncommon and has only been described ommended, since many of these patients juxtafoveolar retinal telangiectasis. Retina 1997;17(2):94-8.
in the literature during the past 25 years; will stabilize without intervention. 14. Potter MJ, Szabo SM, Chan EY, et al. Photodynamic
therapy of a subretinal neovascular membrane in type 2A
hence, many practitioners may not be idiopathic juxtafoveolar retinal telangiectasis. Am J
familiar with or experienced in diagnos- Clinical Pearls Ophthalmol 2002;133(1):149-51.
ing the disorder. IJRT must be part of • IJRT may also be referred to by var- 15. Snyers B, Verougstraete C, Postelmans L, et al.
Photodynamic therapy of subfoveal neovascular mem-
the differential in any case of idiopathic ious names, including idiopathic juxta- brane in type 2A idiopathic juxtafoveolar retinal telangiec-
paramacular hemorrhage, vasculopathy, foveolar, macular, perifoveal or parafoveal tasis. Am J Ophthalmol 2004;137(5):812-9.
macular edema or focal pigment hyper- telangiectasis, depending on the source. 16. Gamulescu MA, Walter A, Sachs H, et al.
Bevacizumab in the treatment of idiopathic macular
trophy, especially in those patients with- All refer to the same syndrome. telangiectasia. Graefes Arch Clin Exp Ophthalmol
out a history of retinopathy or contribu- • IJRT is commonly underdiagnosed. 2008;246(8):1189-93.
tory systemic disease. The findings may appear very similar to
Diagnosis of IJRT may be aided by diabetic retinopathy, and many cases
the use of ancillary testing. OCT can have been incorrectly ascribed to diabet- OCULAR ISCHEMIC
help to identify the abnormal vessels, ic retinopathy. Unfortunately, this misdi- SYNDROME
pigment plaques, retinal crystals, foveal agnosis has also occurred in patients who
atrophy and intraretinal cysts associated were not diabetic. Recognition of this con- Signs and Symptoms
with this disorder.6,7,10 Likewise, fluores- dition can save a patient from unnecessar- As the name implies, ocular ischemic
cein angiography is beneficial in identify- ily undergoing extensive medical testing. syndrome (OIS) results when the blood
ing the anomalous vasculature, particu- • Consider IJRT in cases of mild para- supply to eye is diminished.1-4 It is a pro-
larly in the early stages of Type 2 disease. macular dot and blot hemorrhages in gressive disorder in which chronic
While some have argued that angiogra- patients without ischemic vascular disease hypoperfusion to the eye and orbit pro-
phy is essential in making a definitive such as diabetes and hypertension. Also, duces poor ocular hemodynamics, result-
diagnosis, others suggest that such test- consider this diagnosis in cases of macular ing in a plethora of anterior and posteri-
ing may be unnecessary when a diagnosis and paramacular RPE hyperplasia where or segment findings, including loss of
is apparent via less invasive means.1-4,6 no other cause can be identified. vision, exfoliation syndrome (with the
The natural history of IJRT suggests possibility of exfoliation glaucoma), pre-
1. Abujamra S, Bonanomi MT, Cresta FB, et al. Idiopathic
a slowly progressive disorder. A retro- juxtafoveolar retinal telangiectasis: Clinical pattern in 19 mature cataractogenesis, corneal edema,
spective series of 20 patients over 10 to cases. Ophthalmologica 2000;214(6):406-11. anterior chamber cellular response, ocu-
lar hypotony, dilated but non-tortuous nation of markedly reduced ocular blood OIS does not often lead to increased
GCA and preventing additional loss in • Because of its appearance, OIS is RETINAL ARTERY OCCLUSION
the fellow eye. often mistaken for diabetic retinopathy.
In patients with OIS who develop Unilateral, asymmetric presentation in Signs and Symptoms
neovascularization, panretinal photoco- the absence of lipid should create suspi- Acute retinal artery occlusion is a
agulation (PRP) can be used to decrease cion for OIS over diabetic retinopathy. potentially blinding ophthalmic emer-
the retinal demand for oxygen, thereby gency.1,2 Artery occlusions are catego-
indirectly reducing the need for the faulty 1. Hayreh SS. Neovascular glaucoma. Prog Retin Eye rized into branch, central, cilioretinal, or
Res 2007;26(5):470-85.
vascular supply.15 2. Chen CS, Miller NR. Ocular ischemic syndrome: ophthalmic, depending on the location
New research in Review of clinical presentations, etiology, investigation, of the blockage.3 They are not the result
the area of combi- and management. Compr Ophthalmol Update of a single disease, but instead manifest a
2007;8(1):17-28.
nation treatment 3. Marx JL, Hreib K, Choi IS, et al. Percutaneous carotid combination of chronic systemic abnor-
using PRP and artery angioplasty and stenting for ocular ischemic syn- malities.2,3 As such, no definitive epi-
External view of OIS; the vascular endo- drome. Ophthalmol. 2004;111(12):2284-91. demiology for retinal artery occlusion
note congestion of 4. Foncea Beti N, Mateo I, Díaz La Calle V, et al. The ocu-
conjunctival vascula-
thelial growth fac- lar ischemic syndrome. Clin Neurol Neurosurg has been determined. Rather, it falls
ture and dense lentic- tor inhibitor beva- 2003;106(1):60-2. under the epidemiology of systemic
ular opacification. cizumab resulted 5. Schmidt D. Ocular ischemia syndrome—a malignant heart disease, cardiovascular disease,
course of giant cell arteritis. Eur J Med Res
in rapid decrease 2005;10(6):233-42. smoking, obesity and other chronic or
of IOP and swift regression of neovascu- 6. Detorakis ET, Achtaropoulos AK, Drakonaki EE, et al. episodic contributors including subacute
larization, possibly identifying a new Hemodynamic evaluation of the posterior ciliary circulation bacterial endocarditis, tumors, leukemia,
in exfoliation syndrome and exfoliation glaucoma. Graefes
approach to the problem.15 Arch Clin Exp Ophthalmol 2007;245(4):516-21. corticosteroid injection, polyarteritis
Percutaneous carotid angioplasty with 7. Cohn EJ Jr, Sandager GP, Benjamin ME, et al. nodosa, syphilis, blunt trauma, radiation
stenting has been successfully developed Assessment of ocular perfusion after carotid endarterec- exposure, optic nerve drusen, amniotic
tomy with color-flow duplex scanning. J Vasc Surg
for treating OIS resulting from intracra- 1999;29(4):665-71. fluid embolism and cocaine abuse.3,4
nial carotid artery stenosis.3,16 Another 8. Ino-ue M, Azumi A, Kajiura-Tsukahara Y, et al. Ocular The majority of patients with retinal
modality for relieving the effects of ischemic syndrome in diabetic patients. Jpn J Ophthalmol artery occlusion are older.3 Patients pres-
1999;43(1):31-5.
reduced ocular circulation from carotid 9. Kaiser M, Weyand CM, Björnsson J, et al. Platelet- ent with a chief complaint of sudden,
artery disease is carotid endarterecto- derived growth factor, intimal hyperplasia, and ischemic
my.17-19 Although it has had mixed sup- complications in giant cell arteritis. Arthritis Rheum
1998;41(4):623-33.
port as a treatment for OIS, most reports 10. Munch IC, Larsen M. The ocular ischemic syndrome.
in the literature support its position in Ugeskr Laeger 2005;167(35):3269-73.
the armamentarium of procedures 11. Alizai AM, Trobe JD, Thompson BG, et al. Ocular
ischemic syndrome after occlusion of both external
designed to improve outcomes for carotid arteries. J Neuroophthalmol 2005;25(4):268-72.
OIS.6,18,19 In instances in which OIS is 12. Buettner H, Machemer R. Histopathologic findings in
caused by non-giant cell vasculostenotic human eyes after pars plana vitrectomy and lensectomy.
Arch Ophthalmol 1977;95(11):2029-33.
pathology, reestablishing the appropriate 13. Furino C, Guerriero S, Boscia F, et al. In vivo evidence
vascular supply reduced ocular sequelae of hypotrophic ciliary body in ocular ischemic syndrome
and symptoms.12,15,17-19 by ultrasound biomicroscopy. Ophthal Surg Lasers Imag
2007;38(6):505-7.
14. Hayreh SS, Zimmerman B, Kardon RH. Visual Central retinal artery occlusion.
Clinical Pearls improvement with corticosteroid therapy in giant cell
• Intracranial carotid artery stenosis arteritis. Report of a large study and review of literature. painless vision loss.1-4 In many instances,
Acta Ophthalmol Scand 2002;80(4):355-67.
is a rare cause of ocular ischemic syn- 15. Ehlers JP, Spirn MJ, Lam A, et al. Combination intrav- the loss is noticed upon waking.
drome. Carotid angioplasty and stenting itreal bevacizumab/panretinal photocoagulation versus However, when a branch retinal artery is
now permits lesions to be treated that panretinal photocoagulation alone in the treatment of neo- involved or a cilioretinal artery is pres-
vascular glaucoma. Retina 2008;28(5):696-702.
were previously not amenable to 16. Kawaguchi S, Sakaki T, Iwahashi H, et al. Effect of ent—preserving central vision—patients
endarterectomy. carotid artery stenting on ocular circulation and chronic may complain of shadows in their visual
• Giant cell arteritis must always be ocular ischemic syndrome. Cerebrovasc Dis 2006;22(5- field. Some may report that they have
6):402-8.
considered as the cause of ocular 17. Wolintz RJ. Carotid endarterectomy for ophthalmic experienced episodes of transient visual
ischemic syndrome cases in patients manifestations: Is it ever indicated? J Neuroophthalmol loss before the current episode.3-5
older than 60 years. 2005;25(4):299-302. Concurrent pain is more suggestive of
18. Kawaguchi S, Okuno S, Sakaki T, et al. Effect of
• Lack of perfusion creates a stagnant carotid endarterectomy on chronic ocular ischemic syn- underlying ocular ischemic syndrome
blood in the peripheral retinal microvas- drome due to internal carotid artery stenosis. Neurosurg (carotid circulation) rather than retinal
cular circulation. This leads to mid- 2001;48(2):328-32. artery occlusion.6 Although the etiology
19. Kawaguchi S, Sakaki T, Uranishi R, et al. Effect of
peripheral dot and blot hemorrhages, the carotid endarterectomy on the ophthalmic artery. Acta of retinal artery obstructions is primarily
hallmark of OIS. Neurochir (Wien) 2002;144(5):427-32. embolic, they are not always visible.2
As artery occlusions develop, the fun- edema and necrosis present within min- tion. Anecdotally, the potential for
suggestive of GCA, obtaining ESR and potential for spontaneous visual 4. Opremcak E, Rehmar AJ, Ridenour CD, et al.
Restoration of retinal blood flow via translumenal Nd:YAG
CRP is emergently required. improvement, even without interven- embolysis/embolectomy (TYL/E) for central and branch
In general, anticoagulation therapy is tion. Over a 27 year period, Hayreh and retinal artery occlusion. Retina 2008;28(2):226-35.
the staple of treating patients with artery Zimmerman noted spontaneous visual 5. Schmidt D, Hetzel A, Geibel-Zehender A, et al.
Systemic diseases in non-inflammatory branch and cen-
occlusion secondary to coagulopathy, improvement in some patients with tral retinal artery occlusion—an overview of 416 patients.
hyperviscosity, cardiac or carotid CRAO, dependent upon the classifica- Eur J Med Res 2007;12(12):595-603.
sources.15,17-20 In cases involving GCA, tion and etiology of the occlusion.26 6. Chen CS, Miller NR. Ocular ischemic syndrome:
Review of clinical presentations, etiology, investigation,
lupus or antiphospholipid antibody syn- and management. Compr Ophthalmol Update
drome, immunosupressants may be Clinical Pearls 2007;8(1):17-28.
appropriate.18 • Giant cell arteritis, optic neuritis, 7. Chung YR, Kim JB, Lee K, et al. Retinal artery occlu-
sion in a healthy pregnant patient. Korean J Ophthalmol
Intra-arterial thrombolysis (IAT) rep- retinal vein occlusion, infectious neu- 2008;22(1):70-1.
resents an aggressive approach to treat- roretinitis, vitreous hemorrhage sec- 8. Greven CM, Weaver RG, Owen J, et al. Protein S defi-
ing retinal arterial occlusions, with the ondary to proliferative retinopathy, reti- ciency and bilateral branch retinal artery occlusion.
Ophthalmol 1991;98(1):33-4.
potential to produce superior visual out- nal detachment and retinal vasculitis are 9. Nelson ME, Talbot JF, Preston FE. Recurrent multiple-
comes compared with conventional all potential sources of monocular branch retinal arteriolar occlusions in a patient with protein
treatments.21-24 The use of intravenous vision loss. C deficiency. Graefes Arch Clin Exp Ophthalmol
1989;227(5):443-7.
and intra-arterial thrombolytic agents • Cilioretinal arteries take their blood 10. Kim IT, Choi JB. Occlusions of branch retinal arteri-
such as urokinase has been investigated supply from the choroid, often emerging oles following amniotic fluid embolism. Ophthalmologica
for more than 20 years, but there from the temporal optic nerve and aid- 2000;214(4):305-8.
11. Konareva-Kostianeva M. Neovascular glaucoma.
remains insufficient evidence to support ing in the supply of retinal tissues in the Folia Med (Plovdiv) 2005;47(2):5-11.
its routine use.21-24 A potential side effect vicinity of the macula. In the event that 12. Kergoat H, Hérard ME, Lemay M. RGC sensitivity to
of the treatment is vitreous hemor- a central retinal artery occlusion occurs mild systemic hypoxia. Invest Ophthalmol Vis Sci
2006;47(12):5423-7.
rhage.23 A prospective controlled clinical in the presence of a cilioretinal artery, 13. Wong TY, Mitchell P. The eye in hypertension. Lancet
trial is ongoing in Europe, with the goal these vessels can partially preserve func- 2007;369(9559):425-35.
of providing reliable information and tion over the area of their distribution, as 14. Liem RI, Calamaras DM, Chhabra MS, et al. Sudden-
onset blindness in sickle cell disease due to retinal artery
guidelines on this treatment.22 long as the occlusion does not also affect occlusion. Pediatr Blood Cancer 2008;50(3):624-7.
Hyperbaric oxygen therapy is a pri- the choroidal circulation. 15. Winterkorn JM, Mack P, Eggenberger E. Transient
mary or adjunctive therapeutic modality • Patients with primary antiphos- visual loss in a 60-year-old man. Surv Ophthalmol
2008;53(3):301-5.
that is currently in off-label trials for eye pholipid antibody syndrome may devel- 16. Hayreh SS, Zimmerman MB, Kimura A, et al. Central
diseases.25 Increasing evidence has op retinal artery occlusions and may retinal artery occlusion. Retinal survival time. Exp Eye Res
demonstrated safety and efficacy for use also exhibit episodes of amaurosis 2004;78(3):723-36.
17. Suvajac G, Stojanovich L, Milenkovich S. Ocular
in retinal artery occlusion among other fugax, transient ischemic attack and manifestations in antiphospholipid syndrome. Autoimmun
conditions.25 A newly proposed tech- anterior ischemic optic neuropathy, cil- Rev 2007;6(6):409-14.
nique using Nd:YAG laser to photodis- ioretinal artery occlusion, central retinal 18. Coroi M, Bontas E, Defranceschi M et al. Ocular
manifestations of antiphospholipid (Hughes’) syndrome—
rupt emboli within the central retinal artery occlusion and ophthalmic artery minor features? Oftalmologia 2007;51(3):16-22.
artery and branch retinal arteries may occlusion. Amaurosis fugax, retinal vas- 19. Coroi M, Bontas E, Visan R, et al. Ocular migraine
help achieve rapid reperfusion of the reti- cular thrombosis and optic neuropathy and antiphospholipid antibodies—where we stand?
Oftalmologia 2007;51(3):8-15.
na.4 Translumenal Nd:YAG embolysis are considered the ocular hallmark signs 20. Schmidt D, Hetzel A, Geibel-Zehender A. Retinal
(TYL) or embolectomy (TYE) have of Hughes’ syndrome. Testing for arterial occlusion due to embolism of suspected cardiac
been reported as potential procedures autoimmune factors and antiphospho- tumors—report on two patients and review of the topic.
Eur J Med Res 2005;10(7):296-304.
that can be deployed quickly in cases of lipid antibody syndrome is especially 21. Noble J, Weizblit N, Baerlocher MO, et al. Intra-arte-
retinal nonperfusion secondary to embol- important in younger patients with rial thrombolysis for central retinal artery occlusion: A sys-
ic blockage.4 In one study, following retinal artery occlusion. tematic review. Br J Ophthalmol 2008;92(5):588-93.
22. Biousse V, Calvetti O, Bruce BB, et al. Thrombolysis
TYL, Snellen visual acuity improved by • Heroic measures to restore retinal for central retinal artery occlusion. J Neuroophthalmol
an average of 4.7 lines in 17 of 19 perfusion typically fail in the majority of 2007;27(3):215-30.
patients (89%), and 11 of the patients these cases because many patients delay 23. Weber J, Remonda L, Mattle HP, et al. Selective
intra-arterial fibrinolysis of acute central retinal artery
(58%) gained greater than 4 lines.4 seeking treatment. occlusion. Stroke 1998;29(10):2076-9.
Vitreous hemorrhage and subhyaloid 24. Vallée JN, Paques M, Aymard A, et al. Combined
hemorrhage are potential complications 1. Pokhrel PK, Loftus SA. Ocular emergencies. Am Fam central retinal arterial and venous obstruction: Emergency
Physician 2007;76(6):829-36. ophthalmic arterial fibrinolysis. Radiol 2002;223(2):351-9.
of this treatment, however.4 2. Hayreh SS. Prevalent misconceptions about acute 25. Oguz H, Sobaci G. The use of hyperbaric oxygen
It should be noted that while retinal retinal vascular occlusive disorders. Prog Retin Eye Res therapy in ophthalmology. Surv Ophthalmol
artery occlusion significantly deprives 2005;24(4):493-519. 2008;53(2):112-20.
3. Duker JS. Retinal arterial obstruction. In: Yanoff M, 26. Hayreh SS, Zimmerman MB. Central retinal artery
the retina of oxygen with tissue death Duker JS. Ophthalmology (2nd ed). St Louis, MO: Mosby, occlusion: visual outcome. Am J Ophthalmol. 2005
rapidly esuing, there still remains the 2004, pp. 854-61. Sep;140(3):376-91.
NEURO-OPHTHALMIC DISEASE
NEURO-OPHTHALMIC DISEASE
DORSAL MIDBRAIN brain) contains many structures that can element of managing patients with DMS
SYNDROME be compromised, resulting in the numer- is determining the underlying etiology.
ous clinical signs seen in the syndrome. Treatment options are dictated by the
Signs and Symptoms DMS represents a supranuclear palsy that specific condition. Today, pinealomas are
Dorsal midbrain syndrome (DMS), primarily affects conjugate vertical eye most commonly managed by surgical
also known as Parinaud’s syndrome, pre- movements. It results from damage to the excision with radiation. Chemotherapy is
tectal syndrome, Sylvian aqueduct medial longitudinal fasciculus (MLF), an alternative or adjuvant therapy, depend-
syndrome or Koerber-Salius-Elschnig mainly at the level of the superior collicu- ing upon the nature of the tumor. All cases
syndrome, presents with findings that lus. The rostral interstitial nucleus of the of DMS warrant prompt referral to a qual-
include a vertical gaze disturbance with MLF (riMLF) controls vertical gaze; the ified neurologist and/or neurosurgeon.
paresis, spastic-paretic accommodation, superior colliculus controls vertical sac-
convergence-retraction nystagmus and cades and houses the intercalated neu- Clinical Pearls
light-near dissociated (LND) pupils.1-7 rons, which are associated with pupillo- • The initial presentation of DMS
There may also be bilateral lid retraction motor function. Downgaze paralysis may involve loss of upward saccades in
without lid lag on down gaze (Collier’s results from bilateral lesions involving the isolation of other findings. Pupillomotor
sign), as well as vertical diplopia due to uni- regions located just caudal, medial and dysfunction is another early sign. All of
lateral or bilateral fourth cranial nerve dorsal to the upper poles of the red nuclei, the abovementioned signs need not be
palsies.8-10 Patients will present variably with while upgaze paralysis results from unilat- present to implicate damage to the dor-
these signs and symptoms, and not every eral lesions in or near the posterior com- sal midbrain.
symptom will be present in every patient. missure. Combined downgaze and • Hydrocephalus often ensues in cases
Because of the inability to converge upgaze paralysis results from bilateral of DMS because of aqueductal stenosis.
the eyes, coupled with the accommoda- lesions involving the region related to the In these cases, patients may present with
tive dysfunction, patients presenting whole riMLF on both sides.13 Probable associated symptoms of headache, nausea
with this condition most often complain destruction of the olivary pretectal nucle- and vomiting, transient visual obscura-
of a newfound difficulty with reading or us and the nucleus of the optic tract like- tions, tinnitus, alterations of mental sta-
recent onset diplopia. Headache may be ly abolishes the pupillary light reflex.11 tus and gait disturbance. Papilledema is
reported in cases that have associated Occasionally, damage will involve the typically observed in these patients.
intracranial hypertension.11 Clinical test- midbrain at the level of the inferior col- • DMS is often confused with myas-
ing reveals an inability to look upwards. liculus.The trochlear nuclei (cranial nerve thenia gravis in its early stages because of
Initially, only upward saccades are lost, IV) are located in this area, ventral to the its variable presentation. Pupil involve-
but eventually upward pursuit move- cerebral aqueduct. Their motor fibers ment is never associated with myasthe-
ments fail as well. This finding may be leave the nuclei and decussate within the nia gravis, however, and ocular motility
vague, however, and is best elicited by anterior medullary vellum. Involvement dysfunctions improve following rest.
using an optokinetic nystagmus drum or in this area gives rise to unilateral and Also, ptosis is a common early finding in
tape to test upgaze.1-7 Downgaze paresis bilateral cranial nerve palsies.8-10 myasthenia gravis that is not encoun-
may occur as well, although it occurs less Most often, DMS is associated with tered in DMS.
frequently. Accommodative difficulties pinealoma, a compressive lesion of the • When patients present with pupils
range from intermittent spasms on pineal gland that impinges on the struc- that do not react to light, near function
attempted upgaze to complete accom- tures of the dorsal midbrain in the pre- must be assessed. If the pupils react
modative paresis. Convergence-retrac- tectal area.2,6 Midbrain infarction and properly to near, vertical saccades must
tion nystagmus is easily elicited in these closed head trauma are common etiolo- be examined. When vertical saccades are
patients. Upon attempted upward sac- gies.4,9-11 Other reported causes include abnormal, DMS should be ruled out.
cades, the eyes demonstrate retro dis- obstructive hydrocephalus, congenital
1. Oishi A, Miyamoto K, Yoshimura N. Dorsal midbrain
placement into the orbit, with an associ- aqueductal stenosis, metastatic cancer, syndrome induced by midbrain neurosarcoidosis. Jpn J
ated nystagmus.1,5,7 mesencephalic hemorrhage, multiple Ophthalmol 2008;52(3):236-8.
Bilateral LND pupils are a hallmark sclerosis, A-V malformations, infective 2. Allmer DM, Golis TA. Dorsal midbrain syndrome sec-
ondary to a pineocytoma. Optom 2001;72(4):234-8.
sign of DMS.12 The pupils demonstrate endocarditis, posterior fossa aneurysm, 3. Kato I, Okada T, Akao I, et al. Vertical gaze palsy
no reactivity to light, but do react slowly neurosarcoidosis and neurosyphilis.1,4,8,14-19 induced by midbrain lesions and its structural imaging.
to accommodative stimuli. Less com- Auris Nasus Larynx 1998;25(4):339-47.
4. Clark JM, Albers GW. Vertical gaze palsies from medi-
monly, skew deviations and downbeat Management al thalamic infarctions without midbrain involvement.
nystagmus may be noted. Once DMS is diagnosed, neuroimag- Stroke 1995;26(8):1467-70.
ing of the midbrain must be obtained 5. Serdaru M, Gray F, Lyon-Caen O, et al. Parinaud’s syn-
drome and tonic vertical gaze deviation. 3 anatomo-clinical
Pathophysiology (preferably MRI with contrast medium) observations. Rev Neurol (Paris) 1982;138(8-9):601-17.
The dorsal mesencephalon (mid- to ascertain the cause. The most critical 6. Spalice A, Parisi P, Iannetti P. Paroxysmal tonic up
NEURO-OPHTHALMIC DISEASE
the internal carotid artery are located lat- Management Complications of transphenoidal resec-
eral to the pituitary gland. Patients who present with signs or tion include cerebrospinal fluid rhinor-
Pituitary adenomas are typically symptoms indicative of chiasmal pathol- rhea (discharge from nasal mucous
benign, slow-growing neoplasms of ogy, such as pituitary adenoma, warrant membranes), diabetes insipidus and
epithelial origin.11 In most cases, they prompt neuroimaging and medical con- sinusitis.13
arise from the adenohypophysis (the sultation. The preferred radiologic tech- As an alternative (or adjunctive treat-
anterior lobe of the pituitary gland) and nique is high-resolution dynamic mag- ment) to surgery, fractionated radiother-
are capable of producing both systemic netic resonance imaging (MRI). apy offers a non-invasive option to arrest
and visual signs. The optic chiasm is sit- Contrast enhancement with gadolinium tumor growth in pituitary tumors. The
uated approximately 8–13mm above the helps to further delineate pituitary irreg- usual dose is 50 Gy ± 5 Gy and may be
pituitary gland. The nasal retinal fibers ularities, and is crucial in diagnosing delivered via several techniques, includ-
of each eye (representing temporal visu- microadenomas.12 Computed tomogra- ing external proton beam, cobalt
al field) cross, proceeding into the con- phy (CT) scanning can also be used to gamma-knife or linear accelerator focal
tralateral optic tract, while temporal reti- delineate pituitary abnormalities and stereotactic technology.9 Potential com-
nal fibers (representing nasal visual field) may actually be superior in demonstrat- plications associated with this form of
continue posteriorly uncrossed. Inferior ing calcification within the tumor mass; therapy include radiation-induced
nasal fibers (representing superior tem- however, MRI is substantially better hypopituitarism, cerebrovascular acci-
poral field) decussate within the chiasm than CT at depicting the complex dent, optic nerve damage and non-spe-
anteriorly and superior nasal fibers (rep- anatomy and delicate structures sur- cific neurological dysfunction.14
resenting inferior temporal field) decus- rounding the sella.9 Patients with any Medical therapy is primarily limited to
sate posteriorly. indication of hormonal abnormalities prolactinomas and somatotrophic
Upwardly growing pituitary tumors should undergo pituitary function test- tumors, although in such cases tremen-
that reach appropriate sizes can impinge ing, preferably by a pituitary endocrinol- dous efficacy has been noted, to the point
on the anterior notch of the chiasm at ogist. A neurology consultation may be of excluding other, more invasive treat-
its lowest lying aspect, producing the required in cases of substantial neurolog- ment options. Key medical therapies
classic bitemporal hemianopsia, with ic symptoms, such as seizure, nystagmus, include dopamine agonists (e.g.,
increased density superiorly. Since memory disturbance or impairment of bromocriptine, cabergoline and quinago-
tumor growth is usually asymmetrical, the senses. lide) for hyperprolactinemia, and somato-
the field loss between two eyes is also Therapeutic intervention is aimed at statin analogues (e.g., octreotide and lan-
typically asymmetrical. reducing the tumor mass and normaliz- reotide) and GH antagonists (e.g.,
Pituitary adenomas are differentiated ing hormonal secretion. The three treat- pegvisomant) for acromegaly. The
clinically by size and by the presence or ment modalities that are employed with dopamine agonists have particularly
absence of hormonal hypersecretion. regularity include surgery, radiation and impressive outcomes in 85–90% of
Microadenomas, defined as 10mm or medical (i.e., pharmacologic) therapy. patients, but, unfortunately they are
less in diameter without sellar enlarge- The preferred treatment in any given plagued by substantial adverse side
ment, have little impact on the visual sys- case depends upon the age and health of effects, including nausea and vomiting,
tem or gland function. Macroadenomas, the patient, the size and invasiveness of postural hypotension and dizziness,
which by definition are 10mm or larger, the tumor, and the degree of hormone headache, constipation and depressive
have the capacity to expand beyond the production by the tumor. reactions.2 Thus, despite their efficacy,
sella turcica and induce mass effect Surgical intervention for pituitary these drugs are often intolerable to
symptoms, such as headache and visual adenomas is indicated when there is evi- patients. Also, the practitioner must real-
disturbances.9 Macroadenomas include dence of tumor enlargement, especially ize that the effects of these agents persist
(in order of most common to least com- when growth is accompanied by com- only as long as therapy is continued;
mon): non-secreting adenomas, prolactin pression of the optic chiasm, cavernous hence, these medications must be contin-
secreting (chromaphobe) adenomas, sinus invasion or the development of ued for life, unless other forms of therapy
growth hormone secreting (acidophil) pituitary hormone deficiencies. A trans- are used.
adenomas, ACTH secreting (basophil) sphenoidal or subfrontal transcranial
adenomas and FSH or TSH secreting approach may be used, though the trans- Clinical Pearls
adenomas.2,9 Secreting tumors are usually sphenoidal technique is preferred by the • Although pituitary adenomas are
diagnosed by internists and endocrinolo- vast majority of skilled pituitary neuro- considered benign, they have the capacity
gists. Non-secreting tumors are often surgeons.9 Visual improvement follow- to cause significant morbidity in vision
diagnosed by eyecare practitioners ing treatment is often dramatic, with the and other organ systems. In a small per-
because they produce visual symptoms in greatest degree of improvement occur- centage of patients, pituitary tumors may
the absence of systemic signs. ring within the first few months. be malignant. By definition, these are
referred to as pituitary carcinomas and 8. Kawasaki A, Purvin VA. Photophobia as the present- nomena without affecting acuity, and
ing visual symptom of chiasmal compression. J
represent pituitary tumors with evidence Neuroophthalmol 2002;22(1):3-8.
typically includes other neurologic
of subarachnoid, brain, or systemic 9. Chanson P, Salenave S. Diagnosis and treatment of pitu- symptoms. In some cases, TIA presents
metastasis.12 itary adenomas. Minerva Endocrinol 2004;29(4):241-75. with no visual involvement, and these
10. Chanson P, Young J. Pituitary incidentalomas.
• The differential diagnosis of pitu- Endocrinologist 2003;13(2):124-35.
patients typically present to a neurologist
itary tumor includes craniopharyngioma 11. Minniti G, Esposito V, Piccirilli M, et al. Diagnosis and or hospital emergency room. The pat-
(a slow-growing tumor arising from ves- management of pituitary tumours in the elderly: A review tern demonstrated is often diagnostic for
based on personal experience and evidence of literature.
tigial remnants of Rathke’s pouch), Eur J Endocrinol 2005;153(6):723-35.
location.3 Scotomas may be monocular
meningiomas and gliomas; all of these 12. Kaltsas GA, Nomikos P, Kontogeorgos G, et al. or binocular, idiopathic, altitudinal, sec-
can impinge on the chiasm and present Clinical review: Diagnosis and management of pituitary toral or homonymous.3 Monocular, sec-
carcinomas. J Clin Endocrinol Metab 2005;90(5):3089-99.
with a similar ophthalmic picture. 13. Ahmed S, Elsheikh M, Stratton IM, et al. Outcome of
toral episodes indicate involvement in
Clinical masqueraders can include chron- transphenoidal surgery for acromegaly and its relationship the carotid/ocular circulation.3 Binocu-
ic retrobulbar optic neuritis, toxic/nutri- to surgical experience. Clin Endocrinol (Oxf) lar, homonymous events signify a
1999;50(5):561-7.
tional optic neuropathy, uncorrected 14. Gillam MP, Molitch ME, Lombardi G, et al. Advances
retrochiasmal effect and posterior or ver-
refractive error, normal tension glaucoma in the treatment of prolactinomas. Endocr Rev tebral circulatory issue. Like AF, TIA is
and age-related maculopathy. Misdiag- 2006;27(5):485-534. a sign of vascular disease, making its epi-
nosis is often attributable to an inade- demiology similar to that of AF.1-11
quate history, failure to correlate systemic AMAUROSIS FUGAX AND TIA is on a continuum with AF but is
signs and visual symptoms, or failure to TRANSIENT ISCHEMIC ATTACK considered its own entity because of the
perform adequate testing or follow up. length of time the events last and because
• Bilateral tilted disc syndrome can Signs and Symptoms it reflects influence on more than one
result in a superior bi-temporal field The word amaurosis originates from neurologic area. AF is strictly a local ocu-
defect similar to that seen in pituitary the Greek meaning “darkness.”1 The lar event; TIA represents the beginning
adenoma. Careful ophthalmoscopic eval- word fugax originates from the Latin of a territorial issue. As the name implies,
uation should be performed before more meaning “fleeting.” Hippocrates was the TIA affects a sector of neurologic tissue
invasive testing (such as MRI or pituitary first to use the term amaurosis fugax to momentarily and temporarily, secondary
function testing) is ordered. However, connote blindness in the absence of any to an event or process that interrupts cir-
bitemporal field loss respecting the verti- apparent lesion of the eye.1 Today, the culation.1-11 When the effects of an
cal meridian warrants neuroradiologic term is used to describe an event of episode remain permanently, they cross
investigation even in the presence of tilt- monocular vision loss lasting from sec- the line into the category of cerebrovas-
ed disc syndrome. onds to minutes.1-4 cular accident or stroke.
• In pregnant women, bi-temporal Amaurosis fugax (AF) almost always
visual field loss and headache may signal presents as sudden, painless vision loss, Pathophysiology
pituitary apoplexy (rapid degeneration lasting seconds to minutes, without evi- AF and TIA share the common etiol-
with hemorrhagic necrosis of the pituitary dence of headache, secondary to an ogy of interrupted blood flow either to
gland). Pituitary apoplexy is a potentially embolic event or hemodynamic insuffi- the eye or areas of the brain which sub-
life-threatening condition and warrants ciency, frequently leaving some perma- serve vision.4-8 Patients with common
prompt referral for an MRI with or with- nent remnant.1-9 AF may forecast carotid artery stenosis may be susceptible
out lumbar puncture to rule out subarach- impending retinal hemorrhages, cotton to transient hemodynamic insufficiency
noid hemorrhage from this type of tumor. wool spots, central retinal vein occlusion, of the retina as a result of simultaneous
anterior ischemic optic neuropathy, reti- reductions in blood supplies from both
1. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence nal artery occlusion, ophthalmic artery the external carotid artery and the inter-
of pituitary adenomas: A systematic review. Cancer occlusion or cerebrovascular accident nal carotid artery.2,3
2004;101(3):613-9.
2. Davis JR, Farrell WE, Clayton RN. Pituitary tumours. (CVA).6,10 It is a sign of beginning, TIA may be caused by papilledema,
Reproduc 2001;121(3):363-71. impending or worsening vascular dis- epilepsy, hypertension, diabetes, cardiac
3. Faglia G. Epidemiology and pathogenesis of pituitary ease.11 As such, its epidemiology is non- disease, pregnancy, seizures, blood coag-
adenomas. Acta Endocrinol (Copenh) 1993;129(Suppl
1):S1-S5. specific and is associated with the sys- ulopathy and hyperviscosity syndromes,
4. Monson JP. The epidemiology of endocrine tumours. temic illnesses that induce it, along with the toxic effects of medications, hyper-
Endocr Relat Cancer 2000;7(1):29-36. smoking, hyperlipidemia and age older lipidemia, as well as thrombosis and
5. Kitthaweesin K, Ployprasith C. Ocular manifestations of
suprasellar tumors. J Med Assoc Thai 2008;91(5):711-5. than 64 years.1-12 emboli.11-20 Disorders of clotting, hyper-
6. Bynke H. Pituitary adenomas and their ocular mani- Transient ischemic attack (TIA) may coagulopathy and hyperviscosity, such as
festations: Evidence of cases and clinical findings be characterized by monocular or binoc- antiphospholipid antibody syndrome,
1946–1984. Neuroophthalmol 1986; 6:303-11.
7. Foroozan R. Chiasmal syndromes. Curr Opin ular vision loss lasting minutes to hours, should be considered in young people
Ophthalmol 2003;14(6):325-31. may induce other noticeable visual phe- experiencing either phenomenon.6,14
NEURO-OPHTHALMIC DISEASE
Spontaneous dissection of the cervical management will vary with ultimate the setting of a normal neuro-oph-
internal carotid artery causes territory cause.1-25 Obviously, work must be done thalmic examination.5-7
ischemia and symptoms on the side of in the area of the modifiable risk fac-
dissection. Local signs and symptoms tors: stopping smoking, reducing cho- Clinical Pearls
include head, facial or neck pain, lesterol, lowering blood pressure, man- • Important clinical questions for
Horner’s syndrome, pulsatile tinnitus, aging diabetes and maintaining a patients presenting with the chief com-
cranial nerve palsy (III, IV, V and VI), proper weight. The medical evaluation plaint of an episode of sudden painless
headache, ischemic stroke in 80–84%, should include a complete blood count vision loss include:
transient ischemic attack in 15–16%, with differential and platelets, an ery- – What activities preceded the
amaurosis fugax in 3%, ischemic optic throcyte sedimentation rate (ESR), C- episode?
neuropathy in 4% and retinal infarct in reactive protein (CRP), lipid panel, – Was it one eye or both?
1%.15 Optic disc drusen have also been carotid artery evaluation using transcra- – Was vision completely lost dur-
reported to induce episodes of transient nial Doppler, prothrombin time, acti- ing the episode?
visual interruption via the mechanism of vated partial thromboplastin time, pro- – Was vision blacked out or blurry?
intermittent compression.9 tein S, protein C, antiphospholipid – How long did the episode last?
Retinal migraine is characterized by antibody testing, antinuclear antibody – When vision returned, did it
its vasospastic etiology.3,5-8 Although the and lupus anticoagulant testing, come back suddenly or gradually?
International Headache Society diag- echocardiogram and transesophageal – Did the episode leave any per-
nostic criteria for retinal migraine echocardiogram.16-19 Older patients, manent loss?
requires reversible visual loss, irreversible especially those demonstrating systemic – Has this happened before, and if
visual loss may be part of the retinal symptoms suggestive of giant cell so, how many times?
migraine spectrum, representing an ocu- arteritis (jaw claudication, pain upon – If the episodes are new, what is
lar form infarction.8 palpation of the temporal forehead, their frequency, and is the frequency
Light-induced amaurosis fugax is a anorexia, loss of appetite), should changing?
manifestation of ocular ischemic syn- undergo ESR and CRP immediately.23 – Did a headache occur after the
drome (carotid occlusive syndrome) Ocular management should include episode?
occurring when significant, bilateral, detailed, dilated inspection of the poste- • Retinal migraine is classically seen
carotid artery disease has developed.4 rior pole to rule out the presence of in women of childbearing age and
The frequency of amaurotic episodes emboli and perimetry to determine any includes classic, cluster or complicated
seems to be significantly higher in cases visual field loss. Neuroimaging, such as headache with aura.6 It typically is
involving common carotid artery steno- magnetic resonance imaging and mag- characterized by monocular visual phe-
sis compared against internal carotid netic resonance angiography, may be nomena lasting less than one hour.
artery stenosis and indicates advanced indicated to ascertain a cause. • Acephalic retinal migraine can
disease.2 The systemic management for TIA produce variable visual symptoms in
Giant cell arteritis (GCA) is a possi- and AF resulting from vascular disease is the absence of headache, further com-
ble cause of TIA and AF in the elder- oral anticoagulant therapy. Management plicating the diagnosis.
ly.21 In a classic report on the subject, for systemic autoimmune disease is oral • Light-induced AF from ocular
examining biopsy-proven GCA in a anti-inflammatory therapy with or with- ischemic syndrome is often an indica-
prospective study of 170 patients over a out immune modulation.6 Surgical man- tion that timely carotid surgical inter-
12-year period, amaurosis fugax agement of carotid artery disease can be vention is indicated because of the
occurred in 30.6% of patients. This accomplished via percutaneous angio- major risk for stroke.
underscores the need to consider GCA plasty with stenting or endarterecto- • Amaurosis fugax is a significant
in all patients experiencing transient my.9,24 Patients experiencing AF will symptom with a much higher associa-
vision loss. Uncovering GCA as the need consultation from an internist or tion to extracranial CVA than either
cause of TIA or AF may save patients cardiologist to determine the underlying Hollenhorst plaque or artery occlusion.
from certain catastrophic vision loss cause. Patients experiencing TIA are It warrants immediate investigation.
from central retinal artery occlusion best managed by a neurologist. • Recurrent bouts of AF in elderly
(CRAO), anterior ischemic optic neu- AF must be differentiated from patients may indicate the presence of
ropathy (AION) or cerebrovascular monocular visual loss labeled retinal GCA and impending permanent vision
accident.21,22 migraine.5,6 A true retinal migraine is a loss from retinal artery occlusion or
diagnosis of exclusion that produces a ischemic optic neuropathy.
Management fully reversible monocular visual distur- • AF and TIA are straws that tell us
AF and TIA are symptoms of an bance (classic aura vs. other episodic phe- which way the intracranial wind is
underlying vasculopathic process.1-8 The nomena) in concert with a headache in blowing.
NEURO-OPHTHALMIC DISEASE
of brainstem involvement.7,13 Damage to the third nerve in the cav- regeneration develops, MRI/MRA is
Once the CN III fascicles emerge ernous sinus, superior orbital fissure or required to rule out the presence of a mass
from the brainstem, they form the nerve posterior orbit is unlikely to present as an in the subarachnoid space.3
proper and travel through the subarach- isolated palsy due to the confluence of Children younger than 14 years rarely
noid space parallel to the posterior com- other structures within these areas. have aneurysms, and the majority of third
municating artery. Damage to the third Cavernous sinus involvement will also nerve palsies in this age group are trau-
nerve within the subarachnoid space pro- include possible concurrent pareses of matic or congenital.7 If the patient is
duces an isolated third nerve palsy. The cranial nerve IV, VI and V1, as well as an younger than 50 years and has a non-
main concern in an isolated CN III palsy ipsilateral Horner’s syndrome. The most pupillary-involved, isolated third nerve
occurring within the subarachnoid space common causes of damage in these areas palsy, intracranial angiography is indicat-
is compression of the nerve by an include metastatic disease, inflammation, ed, since ischemic vasculopathy is less
expanding aneurysm of the posterior herpes zoster, carotid artery aneurysm, likely than aneurysm to occur in this age
communicating artery. Additionally pituitary adenoma, pituitary apoplexy and group. If an adult patient of any age pres-
aneurysmal compression can occur from sphenoid wing meningioma.2,3,7 ents with complete or incomplete isolated
the internal carotid, basilar, anterior com- third nerve palsy with pupillary involve-
municating or temporal arteries, though Management ment, it should be considered a medical
to a lesser extent than from the posterior Management of third nerve palsy in emergency and the patient should under-
communicating artery.8,9,14-16 Approxi- the adult depends upon the associated go immediate MRA/MRI or intracranial
mately 15% of isolated CN III palsies findings and etiology. In complicated angiography. In these cases, the cause is
occurring secondary to damage within third nerve palsies in which other neural likely an aneurysm at the junction of the
the subarachnoid area are the result of structures are involved, the patient should internal carotid and posterior communi-
aneurysms.11 Vasculopathic infarct, often undergo MRI scanning to ascertain the cating arteries or at the tip of the basilar
associated with concurrent diabetes or etiology. The scan should be directed to artery. If the aneurysm ruptures, Tthe
hypertension, accounts for 35% of cases the anatomical location as dictated by the patient may die from subarachnoid hem-
of isolated CN III palsy.11 associated findings described above.3 orrhage and brainstem herniation
Aneursymal compression is marked In cases of isolated, complete third through the foramen magnum.
by head or retro-orbital pain and aniso- nerve palsies with no pupillary involve- In cases of CN III palsy caused by
coria with ipsilateral pupil dilation as the ment and in which the patient is older subarachnoid aneurysm, immediate neu-
than 50 years, the main cause is predom- rosurgical intervention is necessary.
inantly ischemic vascular infarct. Giant Common endovascular treatment
cell arteritis is also a potential etiology. involves direct clipping of the aneurysm
Tumor and aneurysm also can produce or embolization with detachable coils.16-17
isolated lesions without pupillary involve-
ment, although this is rare.3 Magnetic res- Clinical Pearls
onance imaging (MRI) and magnetic res- • Isolated third nerve palsy resulting
Right cranial nerve III palsy.
onance angiography (MRA), erythrocyte from ischemic vasculopathy will sponta-
sedimentation rate, C-reactive protein, neously resolve and recover over a period
expanding aneurysm compresses the blood pressure measurement, complete of three to six months. If the palsy fails
pupillomotor fibers within CN III as blood count with differential, blood glu- to resolve in this time, then neuroradio-
well as pain-sensitive dura and other cose testing, antinuclear antibody testing logic studies must be undertaken once
such structures. Approximately one- and syphilis serology are indicated. Close again to determine the true etiology.
third of patients with CN III palsy from pupil observation is required, as pupil • Complete and total CN III palsy in
vascular infarct manifest a small degree involvement may be delayed by five to an adult older than age 50 without pupil
of anisocoria of typically less than 1mm. seven days. This is especially true for involvement is rarely ever caused by an
In contradistinction, aneurysmal com- patients with incomplete CN III palsy aneurysm.
pression typically causes more than 2mm with pupil sparing, because these patients • Patients manifesting an incomplete
of anisocoria.11 Additionally, patients are more likely to have an incipient CN III palsy should be suspected of hav-
developing CN III palsy from aneurys- aneurysm developing.5 In ischemic vascu- ing a developing aneurysm.
mal compression initially may not pres- lar CN III palsy, the pupil will not evolve, • Myasthenia gravis can mimic virtu-
ent with anisocoria or pupil involve- aberrant regeneration will not occur and ally any cranial neuropathy, including
ment.5,8-10 These patients typically the palsy will spontaneously improve or isolated non-pupillary involved third
present initially with an incomplete palsy resolve over the course of three to six nerve palsies. It must remain a possible
that evolves and develops pupil dilation months.3,11 If the palsy shows no improve- diagnosis when encountering a third
over several days.3,7, 11 ment over six to eight weeks or if aberrant nerve palsy, especially when the course is
variable or atypical. nerve dysfunction in cases of oculomotor palsy. Jpn J ately preceding development of the CN
Ophthalmol 2008;52(1):32-5.
• There will always be pain in 12. Takeuchi S, Takasato Y, Masaoka H, et al. Brain
IV palsy. The trauma need not be major;
aneurysmal compression. In ischemic Nerve 2008;60(5):555-8. relatively minor injuries can precipitate
vascular CN III palsies, however, pain is 13. Adams ME, Linn J, Yousry I. Pathology of the ocular CN IV palsy.2,3,12-14 In cases of longstand-
motor nerves III, IV, and VI. Neuroimaging Clin N Am
frequent but may be absent, and it is typ- 2008;18(2):261-82.
ing decompensated CN IV palsy, the
ically less severe than with aneurysmal 14. White JB, Layton KF, Cloft HJ. Isolated third nerve inciting trauma may have been many
compression. palsy associated with a ruptured anterior communicating years antecedent.
artery aneurysm. Neurocrit Care 2007;7(3):260-2.
• Consider GCA as a cause of CN 15. Aiba T, Fukuda M. Unilateral oculomotor nerve pare-
III palsy in older patients. sis associated with anterior communicating artery Pathophysiology
• Ischemic vascular CN III palsy aneurysm rupture—two case reports. Neurol Med Chir The fourth cranial nerve nucleus is
(Tokyo) 2003;43(10):484-7.
does not progress to develop aberrant 16. Asakura K, Tasaki T, Okada K. A case of unruptured
located in the dorsal mesencephalon.
regeneration. anterior temporal artery aneurysm showing pupil-sparing Nerve fibers decussate and exit the brain
• Anisocoria in ischemic infarction oculomotor palsy. No Shinkei Geka 1986;14(6):777-82. stem dorsally into the subarachnoid
17. Inamasu J, Nakamura Y, Saito R, et al. Early resolu-
CN III palsy is nominal, typically less tion of third nerve palsy following endovascular treatment
space. The nerve then courses around the
than 1mm between the eyes. In con- of a posterior communicating artery aneurysm. J brain to enter the cavernous sinus, supe-
tradistinction, the anisocoria from Neuroophthalmol 2002;22(1):12-4. rior orbital fissure and orbit to innervate
18. Ahn JY, Han IB, Yoon PH, et al. Clipping vs. coiling of
aneurysmal compression typically posterior communicating artery aneurysms with third
the superior oblique muscle. Damage to
exceeds 2mm. nerve palsy. Neurol 2006;66(1):121-3. the fourth nerve nucleus or its fascicles
• Pupil-involved CN III palsy in within the brain stem produces a con-
adults is one of the few true medical tralateral fourth nerve palsy, along with
emergencies seen in eye care. These CRANIAL NERVE IV PALSY the possible associated signs of light-near
patients must be sent to the hospital dissociated pupils, retraction nystagmus,
immediately for neurosurgical consult. Signs and Symptoms upgaze palsy, Horner’s syndrome and/or
A patient with cranial nerve (CN) IV internuclear ophthalmoplegia. Bilateral
1. Satyarthee GD, Mahapatra AK. Unusual neuro-oph-
thalmic presentation of anterior communicating artery palsy will typically present with com- fourth nerve palsies are possible as well.
aneurysm with third nerve paresis. J Clin Neurosci plaints of vertical diplopia, which worsens The main causes of damage to the fourth
2004;11(7):776-8. if the patient tries to read. There may be nerve in this area are hemorrhage, infarc-
2. Bahmani Kashkouli M, Khalatbari MR, Yahyavi ST, et
al. Pituitary apoplexy presenting as acute painful isolated an inability to look down and in. There tion, trauma, hydrocephalus and
unilateral third cranial nerve palsy. Arch Iran Med may also be a component of horizontal demyelinization.9,14
2008;11(4):466-8. diplopia as a lateral phoria becomes man- The fourth nerve is especially prone to
3. Yanovitch T, Buckley E. Diagnosis and management of
third nerve palsy. Curr Opin Ophthalmol 2007;18(5):373-8. ifest due to the vertical dissociation.1-4 trauma as it exits the brain stem and
4. Delengocky T, Bui CM. Complete ophthalmoplegia The chin is often tucked downwards courses through the subarachnoid space.
with pupillary involvement as an initial clinical presentation (moved into the field of the dysfunction- In contrast to third nerve palsies with an
of herpes zoster ophthalmicus. J Am Osteopath Assoc
2008;108(10):615-21. al muscle) as well. The patient may note etiology in subarachnoid space, fourth
5. Takahashi M, Kase M, Suzuki Y, et al. Incomplete ocu- greater diplopia or visual discomfort nerve palsies are rarely the result of
lomotor palsy with pupil sparing caused by compression when head tilting toward the side of the aneurysmal compression.The most com-
of the oculomotor nerve by a posterior communicating
posterior cerebral aneurysm. Jpn J Ophthalmol palsy. Commonly, the patient develops a mon causes of damage to the fourth
2007;51(6):470-3. compensatory head tilt opposite to the nerve in this region are trauma and
6. Capó H, Warren F, Kupersmith MJ. Evolution of oculo- affected superior oblique muscle. ischemic vasculopathy.3
motor nerve palsies. J Clin Neuroophthalmol
1992;12(1):21-5. Visual acuity is unaffected and there is Due to the large number of other neu-
7. Richards BW, Jones FR Jr, Younge BR. Causes and very rarely any concurrent pain. Ocular ral structures that accompany the fourth
prognosis in 4,278 cases of paralysis of the oculomotor, motility testing with the alternate cover nerve as it travels through the cavernous
trochlear, and abducens cranial nerves. Am J Ophthalmol
1992;113(5):489-96. test will reveal a hyperphoric or hyper- sinus and superior orbital fissure, it is
8. Kasoff I, Kelly DL Jr. Pupillary sparing in oculomotor tropic deviation that will increase in con- unlikely that patients will exhibit isolated
palsy from internal carotid aneurysm. Case report. J tralateral gaze, reduce in ipsilateral gaze, fourth nerve palsy from damage within
Neurosurg 1975;42(6):713-7.
9. Kissel JT, Burde RM, Klingele TG, et al. Pupil-sparing increase on ipsilateral head tilt and these areas. More likely, there will be a
oculomotor palsies with internal carotid-posterior com- decrease on contralateral head tilt. In concomitant palsy of cranial nerves III
municating artery aneurysms. Ann Neurol bilateral cranial nerve IV palsy, the patient and VI. Common causes of damage to
1983;13(2):149-54.
10. Saito R, Sugawara T, Mikawa S, et al. Pupil-sparing will manifest a hyperdeviation which the fourth nerve in these areas are herpes
oculomotor nerve paresis as an early symptom of unrup- reverses in opposite gaze. The hyperdevi- zoster, inflammation of the cavernous
tured internal carotid-posterior communicating artery ation increases on ipsilateral head tilt.5-8 sinus or posterior orbit, meningioma,
aneurysms: Three case reports. Neurol Med Chir (Tokyo)
2008;48(7):304-6. Frequently there is concurrent hyper- metastatic disease, pituitary adenoma
11. Akagi T, Miyamoto K, Kashii S, et al. Cause and prog- tension and/or diabetes.9-11 Often, there and carotid cavernous fistula.15 Trauma to
nosis of neurologically isolated third, fourth, or sixth cranial will be a history of head trauma immedi- the head or orbit can cause damage to the
NEURO-OPHTHALMIC DISEASE
trochlea with resultant superior oblique management beyond periodic observa- 8. Straumann D, Bockisch CJ, Weber KP. Dynamic
aspects of trochlear nerve palsy. Prog Brain Res
muscle dysfunction. tion and either occlusion or press-on 2008;171:53-8.
Trauma and vascular disease are consid- prism therapy is required.2,3 In some 9. Park UC, Kim SJ, Hwang JM, et al. Clinical features
ered the main causes of acquired CN IV cases, recovery does not occur.2,3 In these and natural history of acquired third, fourth, and sixth cra-
nial nerve palsy Eye 2008;22(5):691-6.
palsy.14,15 However, there have been num- cases, permanent prism (ground into the 10. Trigler L, Siatkowski RM, Oster AS, et al. Retinopathy
erous reports of other potential causes of spectacle lenses), muscle surgery or botu- in patients with diabetic ophthalmoplegia. Ophthalmol
isolated CN IV palsy, including multiple linum injections may be considered.22 2003;110(8):1545-50.
11. Acaroglu G, Akinci A, Zilelioglu O. Retinopathy in
sclerosis, polycythema vera, cat-scratch patients with diabetic ophthalmoplegia. Ophthalmologica
disease and, rarely, metastatic disease.15-21 Clinical Pearls 2008;222(4):225-8.
• Cases of true vertical diplopia can 12. Dhaliwal A, West AL, Trobe JD, et al. Third, fourth,
Management be considered a fourth nerve palsy until and sixth cranial nerve palsies following closed head
injury. J Neuro-ophthalmol 2006;26(1):4-10.
A fourth nerve palsy often presents proven otherwise. 13. Ishizaki E, Kurokawa Y. A case of solitary and unilat-
suddenly but may additionally result from • If the presenting motility of a eral trochlear nerve palsy due to a blunt head impact.
Rinsho Shinkeigaku 2003;43(9):571-3.
decompensation of a longstanding or patient is a hyperdeviation in one eye 14. de Camargo GB, Hida WT, Goldchmit M, et al.
congenital palsy. To differentiate these that increases on opposite gaze and ipsi- Paralytic strabismus: Review of 24 years at “Santa Casa
two types of palsies, old photographs of lateral head tilt, the cause is nearly de São Paulo.” Arq Bras Oftalmol 2007;70(4):585-7.
15. Richards BW, Jones FR Jr, Younge BR. Causes and
the patient (such as a drivers license) always CN IV palsy. prognosis in 4,278 cases of paralysis of the oculomotor,
should be examined. A patient with a • Myasthenia gravis can mimic CN trochlear, and abducens cranial nerves. Am J Ophthalmol
decompensated longstanding palsy will IV palsy and must always be considered. 1992;113(5):489-96.
16. Tsuda H, Ito T, Yoshioka M, et al. Isolated trochlear
present with a compensatory head tilt. • Bilateral CN IV palsy localizes nerve palsy in herpes zoster ophthalmicus. Intern Med
Further, patients with decompensated damage to the dorsal mesencephalon. 2007;46(8):535-6.
longstanding fourth nerve palsies will • In children, nearly all cases of isolat- 17. Mielke C, Alexander MS, Anand N, et al. Isolated
bilateral trochlear nerve palsy as the first clinical sign of a
have an exaggerated vertical fusional abil- ed fourth nerve palsy are either congeni- metastatic bronchial carcinoma. Am J Ophthalmol
ity. Longstanding fourth nerve palsies tal or traumatic. In adults, nearly all iso- 2001;132(4):593-4.
typically have a benign course and no fur- lated acquired fourth nerve palsies can be 18. Lavin PJ, Donahue SP, Jacobson DM, et al. Isolated
trochlear nerve palsy in patients with multiple sclerosis.
ther management is necessary. ascribed to trauma or vascular disease. Neurol 2000;55(2):321-2.
In the case of complicated fourth Rarely is tumor or aneurysm a cause.The 19. Jacobson DM, Moster ML, Eggenberger ER, et al.
nerve palsies—those that present with majority of fourth nerve palsies follow a Isolated trochlear nerve palsy in patients with multiple
sclerosis. Neurol 1999;53(4):877-9.
other concurrent neurological dysfunc- benign course. 20. Jones MM, Clement CI, Rowe DB. Isolated trochlear
tion—the patient should undergo neuro- • When encountering isolated fourth nerve palsy as a presenting feature of primary poly-
radiological studies dictated by the nerve palsy, delay prescribing permanent cythemia rubra vera. Clin Experiment Ophthalmol
2004;32(3):339-40.
accompanying signs and symptoms. In prisms for at least three months to allow 21. Müller D, Neubauer BA, Waltz S, et al.
the case of isolated fourth nerve palsies for the palsy to recover. Otherwise, Neuroborreliosis and isolated trochlear palsy. Eur J
caused by recent trauma, the patient glasses with permanent prism correction Paediatr Neurol 1998;2(5):275-6.
22. Bagheri A, Eshaghi M. Botulinum toxin injection of
should undergo neuroradiological studies can induce vertical diplopia should the the inferior oblique muscle for the treatment of superior
of the head to dismiss the possibility of a palsy recover. oblique muscle palsy. J AAPOS 2006;10(5):385-8.
concurrent subarachnoid hemorrhage. If
1. Staubach F, Lagrèze WA. Oculomotor, trochlear, and
the fourth nerve palsy is not associated abducens nerve palsies. Ophthalmologe 2007;104(8):
with recent trauma, a history of past trau- 733-46. CRANIAL NERVE VI PALSY
ma should be investigated. If the fourth 2. Akagi T, Miyamoto K, Kashii S, et al. Cause and prog-
nosis of neurologically isolated third, fourth, or sixth cra-
nerve palsy is the result of previous trau- nial nerve dysfunction in cases of oculomotor palsy. Jpn Signs and Symptoms
ma and has recently decompensated, the J Ophthalmol 2008;52(1):32-5. A patient with isolated, unilateral,
diplopia can be managed by the place- 3. Hoya K, Kirino T. Traumatic trochlear nerve palsy fol- acute onset cranial nerve (CN) VI palsy
lowing minor occipital impact—four case reports. Neurol
ment of vertical prisms in spectacles. If Med Chir (Tokyo) 2000;40(7):358-60. will present with horizontal uncrossed
the patient is elderly and has a fourth 4. von Noorden GK, Murray E, Wong SY. Superior diplopia that worsens at distance in
nerve palsy of recent origin, an ischemic oblique paralysis. A review of 270 cases. Arch either right or left gaze depending upon
Ophthalmol 1986;104(12):1771-6.
vascular evaluation should be undertaken 5. Baumeister E. Contribution to the diagnosis of the involved eye.The patient will have an
to determine whether he or she has dia- trochlear paresis (first description of Bielschowsky head- abduction deficit in the involved eye and
betes and hypertension. Giant cell arteri- tilt test). Strabis 2003;11(2):129-30. either an non-comitant esophoric or
6. Simonsz HJ, Crone RA, van der Meer J, et al.
tis should also be considered and appro- Bielschowsky head-tilt test—I. Ocular counterrolling and esotropic posture.1,2 If the palsy is isolat-
priate history and testing should then Bielschowsky head-tilt test in 23 cases of superior ed, there will be neither visual acuity nor
occur. If the palsy is caused by vascular oblique palsy. Vision Res 1985;25(12):1977-82. visual field loss. There may be some
7. Gräf M, Krzizok T, Kaufmann H. Head-tilt test in uni-
infarct, then it will spontaneously resolve lateral and symmetric bilateral acquired trochlear nerve degree of head or retro-orbital pain pres-
over three to six months and no further palsy. Klin Monatsbl Augenheilkd 2005;222(2):142-9. ent, dependent upon the cause.
There are three distinct demographic noid space, ascends the clivus and enters patient profile and palsy. In one large
groups that develop CN VI palsy. Most the cavernous sinus. Within the sub- population-based study, the four most
patients developing acute CN VI palsy arachnoid space, the sixth nerve may be common causes were idiopathic, hyper-
are older. This group often has a concur- stretched against the clivus if the brain tension alone, coexistent diabetes and
rent history of hypertension and/or dia- stem herniates through the foramen hypertension and trauma.6
betes.3-5 The peak incidence occurs in the magnum due to increased intracranial Detailed presenting and medical his-
seventh decade of life.6 Children are also pressure.This may induce a bilateral sixth tory must be obtained as well as a neuro-
prone to develop CN VI palsy. The cause nerve palsy (which is often intermittent) logic examination upon presentation.
may range from benign, such as viral ill- and papilledema.13 The sixth nerve pass- Each case of CN VI palsy should be
ness or trauma, to malignant.7-11 The es over the petrous apex of the temporal classified as traumatic or non-traumatic.
third group consists of adults aged 20–50 bone; damage here can result in a sixth Non-traumatic cases should be subdi-
years. This group is more likely to have nerve palsy, facial pain, and hearing loss. vided as neurologically isolated or non-
neurologically complicated CN VI This is the result of inflammation of the neurologically isolated.6 Additionally,
palsies involving other cranial nerves.12,13 temporal bone (Gradenigo’s syndrome) patients should be ascribed to one of
In contrast to older adults, vascular dis- or nasopharyngeal carcinoma.16,21 Within three groups: children, young adults, and
ease such as diabetes and hypertension the cavernous sinus, the sixth nerve is older adults.6
are uncommon in this group, which typ- joined by the oculosympathetic nerves, as A non-neurologically isolated sixth
ically exhibits more serious conditions well as CN III, IV and VI. Damage here nerve palsy involving any of the above-
such as central nervous system (CNS) mentioned neurological signs indicates
mass lesions and multiple sclerosis.13-15 the need for an MRI of the suspect area
Because various cancers have been as well as a cerebrospinal fluid analysis.
associated with CN VI palsy, patients Non-neurologically isolated CN VI
may present with a pre-existing history of palsies are commonly caused by cere-
malignant disease. However, CN VI palsy brovascular accidents involving the pons,
may be the premonitory sign of cancer in aneurysm (typically within the cav-
some patients. Carcinoma in particular ernous sinus) or neoplasm.6 While neu-
has been associated with the development rologically complicated CN VI palsy has
of CN VI palsy, either through direct a high likelihood of a serious cause such
Cranial nerve VI palsy with resultant abduction
invasion from the nasopharnyx or metas- deficit. as neoplasm, isolated CN VI palsy actu-
tasis from the prostate or other sites.16-21 ally has a very low risk (2% in one series)
Other less common associations with CN will yield a sixth nerve palsy and Horner’s of being caused by a neoplasm.6
VI palsy include herpes zoster, temporal syndrome, as well as possibly concurrent In children, sixth nerve palsy can
arteritis, Lyme disease, sarcoidosis, pitu- CN III and IV palsy.19,20,29 The etiology occur from a presumed viral cause and
itary tumor, aneurysm, inflammation and may be aneurysm, meningioma, pituitary has an excellent prognosis.9,10 However,
ophthalmoplegic migraine.22-28 adenoma, inflammation or fistula.30-33 nearly one-half of all CN VI palsies in
The sixth nerve is also vulnerable to children result from neoplastic disease,
Pathophysiology ischemic infarct from diabetes and notably pontine glioma.8,11 Thus, neuro-
CN VI arises in the pons in close asso- hypertension; this remains a prime cause logic evaluation and consultation is
ciation with the facial nerve and parame- of isolated sixth nerve palsy. urgent in this group, and the cause of the
dian pontine reticular formation (PPRF). Although CN VI can be affected in palsy should not be presumed benign.11
Because of this arrangement, damage to many areas through its course from the In younger adults, CN VI palsy is
the sixth nerve within the brain stem can pons to the orbit, a significant number of likely to be caused by serious underlying
produce a sixth nerve palsy along with a cases will have no conclusive etiology, disease. In this group, CNS mass lesions
facial nerve palsy or internuclear oph- despite extensive medical evaluation.2-4,6,13 and multiple sclerosis account for 33%
thalmoplegia. Associated findings may As many as one-third of CN VI palsies and 24% of CN VI palsies, respectively.
also include leg paralysis with sixth nerve will remain idiopathic.6 13
Idiopathic CN VI palsies account for
palsy (Raymond’s syndrome) or leg 13% of cases and vascular disease only
paralysis, facial paralysis and sixth nerve Management 4%.13 It should be noted that CN VI
palsy (Millard-Gubler syndrome). These The most important consideration in palsy caused by CNS mass lesions in
additional findings identify the location the management of patients with acute young adults involve other cranial neu-
of damage as the pons, in which ischemic onset CN VI palsy involves identifying ropathies and are not isolated. Thus,
infarct, tumor and demyelinization are the causative factor efficiently and cost- neuroimaging is highly recommended in
the common causes.3,4 effectively. Doing so involves under- this group.
CN VI travels through the subarach- standing common causes for each In adults older than 50 years with an
NEURO-OPHTHALMIC DISEASE
isolated sixth nerve palsy, an evaluation and lateral rectus underaction can be said cle palsy, facial numbness and ataxia as the initial mani-
festation of multiple sclerosis. J Natl Med Assoc
for ischemic vascular diseases such as only to have an abduction deficit. A neg- 2008;100(5):572-4.
diabetes and hypertension should be ative forced duction test ascribes the 16. Marchese-Ragona R, Maria Ferraro S, Marioni G, et
undertaken, since these are the most motility to CN VI palsy. al. Abducent nerve paralysis: first clinical sign of clivus
metastasis from tonsillar carcinoma. Acta Otolaryngol
likely causes.2-6 If the patient is older • There is a very low risk of acute iso- 2008;128(6):713-6.
than 60 years, an erythrocyte sedimenta- lated CN VI palsy being caused by a 17. Malloy KA. Prostate cancer metastasis to clivus
tion rate (ESR) should be ordered to rule neoplasm in an older adult. causing cranial nerve VI palsy. Optom 2007;78(2):55-62.
18. O’Boyle JE, Gardner TA, Oliva A, et al. Sixth nerve
out giant cell arteritis. In cases of isolat- • Acute CN VI palsies in children are palsy as the initial presenting sign of metastatic prostate
ed CN VI palsy in older adults with a often harbingers of serious disease such cancer. A case report and review of the literature. J Clin
history of diabetes or hypertension, neu- as cancer, and they must be promptly Neuroophthalmol 1992;12(3):149-53.
19. Hirao M, Oku H, Sugasawa J, et al. Three cases of
roimaging and other extensive evalua- investigated. abducens nerve palsy accompanied by Horner syndrome
tion can be deferred, unless the palsy • Non-neurologically isolated CN VI Nippon Ganka Gakkai Zasshi 2006;110(7):520-4.
progresses, fails to improve over three palsies are often associated with CNS 20. Tsuda H, Ishikawa H, Asayama K, et al. Abducens
nerve palsy and Horner syndrome due to metastatic tumor
months, or other neurologic complica- mass lesions and should be promptly in the cavernous sinus. Intern Med 2005;44(6):644-6.
tions develop. Ischemic vascular palsies evaluated. 21. Ilhan O, Sener EC, Ozyar E. Outcome of abducens
typically progress over several days, but • Acute CN VI palsy in a young adult nerve paralysis in patients with nasopharyngeal carcino-
ma. Eur J Ophthalmol 2002;12(1):55-9.
progression over two weeks warrants is not commonly caused by microvascu- 22. Arai M, Katsumata R. Temporal arteritis presenting
neurioimaging.6 lar infarct but by more serious disease with headache and abducens nerve palsy. Report of a
Spontaneous recovery of CN VI palsy such as multiple sclerosis and CNS mass case. Rinsho Shinkeigaku 2007;47(7):444-6.
23. Berlit P. Isolated and combined pareses of cranial
is common, especially if the etiology is lesions; therefore, it should be promptly nerves III, IV and VI. A retrospective study of 412 patients.
idiopathic, traumatic or microvascu- investigated. J Neurol Sci 1991;103(1):10-5.
lar.3,4,6,13,34 Resolution of CN VI palsy is 24. Kim SH, Lee KC, Kim SH. Cranial nerve palsies
1. Goodwin D. Differential diagnosis and management of accompanying pituitary tumour. J Clin Neurosci
typically complete by three to six acquired sixth cranial nerve palsy. Optom 2006;77(11): 2007;14(12):1158-62.
months, although some cases may take 534-9. 25. Nagasawa H, Iseki C, Wada M, et al. Abducens
longer to resolve. CN VI palsies associ- 2. Staubach F, Lagrèze WA. Oculomotor, trochlear, and nerve palsy as the first manifestation of cavernous sinus
abducens nerve palsies. Ophthalmologe 2007;104(8): sarcoidosis. Rinsho Shinkeigaku 2005;45(1):38-40.
ated with CNS mass lesions tend to have 733-46. 26. Iwao K, Kobayashi H, Okinami S. Case of herpes
a worse prognosis for spontaneous 3. Richards BW, Jones FR Jr, Younge BR. Causes and zoster ophthalmicus with abducent palsy: the cause and
recovery.6,13 In cases where complete prognosis in 4,278 cases of paralysis of the oculomotor, magnetic resonance imaging findings. Nippon Ganka
trochlear, and abducens cranial nerves. Am J Ophthalmol Gakkai Zasshi 2006;110(3):193-8.
recovery does not occur, Fresnel prism 1992;113(5):489-96. 27. Kindstrand E. Lyme borreliosis and cranial neuropa-
correction may alleviate diplopia and 4. Rush JA, Younge BR. Paralysis of cranial nerves III, IV, thy. J Neurol 1995;242(10):658-63.
visual discomfort. More aggressive ther- and VI. Cause and prognosis in 1,000 cases. Arch 28. Vasconcelos LP, Stancioli FG, Leal JC, et al.
Ophthalmol 1981;99(1):76-9. Ophthalmoplegic migraine: A case with recurrent palsy of
apy in non-remitting cases includes stra- 5. Acaroglu G, Akinci A, Zilelioglu O. Retinopathy in the abducens nerve. Headache 2008;48(6):961-4.
bismus surgery or medial rectus injection patients with diabetic ophthalmoplegia. Ophthalmologica 29. Tsuda H, Ishikawa H, Kishiro M, et al. Abducens nerve
with botulinum toxin (Botox).35-37 2008;222(4):225-8. palsy and postganglionic Horner syndrome with or without
6. Patel SV, Mutyala S, Leske DA, et al. Incidence, asso- severe headache. Intern Med 2006;45(14):851-5.
ciations, and evaluation of sixth nerve palsy using a pop- 30. Kupersmith MJ, Stiebel-Kalish H, Huna-Baron R, et
Clinical Pearls ulation-based method. Ophthalmol 2004;111(2):369-75. al. Cavernous carotid aneurysms rarely cause subarach-
• The etiology of isolated CN VI 7. Janssen K, Wojciechowski M, Poot S, et al. Isolated noid hemorrhage or major neurologic morbidity. J Stroke
abducens nerve palsy after closed head trauma: a pedi- Cerebrovasc Dis 2002;11(1):9-14.
palsy in the adult is undetermined in a atric case report. Pediatr Emerg Care 2008;24(9):621-3. 31. Wu HC, Ro LS, Chen CJ, et al. Isolated ocular motor
significant number of cases, despite full 8. Broniscer A, Laningham FH, Sanders RP, et al. Young nerve palsy in dural carotid-cavernous sinus fistula. Eur J
diagnostic evaluation. age may predict a better outcome for children with diffuse Neurol 2006;13(11):1221-5.
pontine glioma. Cancer 2008 1;113(3):566-72. 32. Lee KY, Kim SM, Kim DI. Isolated bilateral abducens
• Vasculogenic CN VI palsies can be 9. Cohen HA, Nussinovitch M, Ashkenazi A, et al. Benign nerve palsy due to carotid cavernous dural arteriovenous
expected to progress over several days, abducens nerve palsy of childhood. Pediatr Neurol fistula. Yonsei Med J 1998;39(3):283-6.
but they will not worsen over two or 1993;9(5):394-5. 33. Ogawa G, Tanabe H, Kanzaki M, et al. Two cases of
10. Vallée L, Guilbert F, Lemaitre JF, et al. Benign paraly- idiopathic carotid-cavernous fistula with headache and
more weeks. Such a clinical course sug- sis of the 6th cranial nerve in children. Ann Pediatr (Paris) ophthalmoplegia. Rinsho Shinkeigaku 2007;47(8):516-8.
gests alternate etiologies. 1990;37(5):303-5. 34. Holmes JM, Droste PJ, Beck RW. The natural histo-
• Myasthenia gravis may mimic a 11. Lee MS, Galetta SL, Volpe NJ, et al. Sixth nerve ry of acute traumatic sixth nerve palsy or paresis. J
palsies in children. Pediatr Neurol 1999;20(1):49-52. AAPOS 1998;2(5):265-8.
sixth nerve palsy and should always be 12. Brinar VV, Habek M, Ozretiç D, et al. Isolated non- 35. Kao LY, Chao AN. Subtenon injection of botulinum
considered in the differential diagnosis, traumatic abducens nerve palsy. Acta Neurol Belg toxin for treatment of traumatic sixth nerve palsy. J Pediatr
especially if the palsy takes on a variable 2007;107(4):126-30. Ophthalmol Strabis 2003;40(1):27-30.
13. Peters GB 3rd, Bakri SJ, Krohel GB. Cause and 36. Holmes JM, Leske DA, Christiansen SP. Initial treat-
course with exacerbations and remis- prognosis of nontraumatic sixth nerve palsies in young ment outcomes in chronic sixth nerve palsy. J AAPOS
sions. However, routine diagnostic test- adults. Ophthalmol 2002;109(10):1925-8. 2001;5(6):370-6.
ing is not indicated unless the patient’s 14. Barr D, Kupersmith MJ, Turbin R, et al. Isolated sixth 37. Gómez De Liaño Sánchez P , Villarejo Díaz-Maroto I,
nerve palsy: an uncommon presenting sign of multiple Gómez De Liaño Sánchez R, et al. Treatment of sixth
history suggests myasthenia gravis. sclerosis. J Neurol 2000;247(9):701-4. nerve palsy of traumatic or tumor etiology using botulinum
• A patient with horizontal diplopia 15. Mitchell JP, Beer J, Yancy A, et al. Lateral rectus mus- toxin. Arch Soc Esp Oftalmol 2000;75(7):471-6.
OCULOSYSTEMIC DISEASE
MYASTHENIA GRAVIS gia and slurred speech, the presence of reserved for immunocompetent
fluctuating dysphonia (changing of the patients with generalized MG who
Signs and Symptoms voice tone) is an under-recognized lack muscle AChR binding, AChR
Myasthenia gravis (MG) takes its sign.3 “Dropped head sign” or weakness modulating or MuSK antibodies at
meaning from the Greek words myo, in the neck muscles creating an inabil- presentation and again at a follow-up
meaning muscle, and asthenia, mean- ity to raise the head has also been rec- 12 months later.14
ing weakness.1 The condition is char- ognized as a potential sign of impend- The predilection of myasthenia to
acterized as a chronic autoimmune ing MG.9 Myasthenic crisis is the attack ocular muscles may be related to
disease of the neuromuscular junction catastrophic failure of the skeletal mus- differences between limb muscle and
which leads to varying degrees of cles involved in respiration.10 Patients extraocular muscle physiology, func-
weakness and fatigability in the skele- in myasthenic crisis develop acute res- tion or antigenicity.15 In simpler terms,
tal muscles.2,3 It affects men and piratory failure and require prompt air- the autoantibodies involved in the
women equally, though mostly older way protection in the form of ventila- pathophysiology, for reasons that
men and women in their second or tion support.12 remain unclear, prefer the receptors of
third decade.3,4 It is not known to be the eye muscles to the skeletal muscles
genetically transmitted.3-5 Prevalence Pathophysiology of the body.15
rates for MG approach 1 in 5,000 MG results from an antibody- MG has a well-established associa-
individuals.6 The disease may affect mediated, T-cell–dependent immuno- tion with thymus gland pathology and
any muscle of the body, including the logic attack on the endplate region of the paraneoplastic syndrome thymo-
muscles of the eye. MG may involve the postsynaptic membrane.6 As the ma.13 Thymoma (tumorous infiltration
just the muscles of the body without receptors which receive the neuro- of the gland by nonmalignant or
affecting the muscles of the eye (gen- transmitter acetylcholine become malignant cells) is found in approxi-
eralized myasthenia) or just the mus- degraded, the signal intended to mately 10–15% of patients with myas-
cles of the eye without affecting the invoke a muscle movement cannot be thenia gravis.15,16
muscles of the body (ocular myasthe- propagated or maintained, and acetyl-
nia).2-8 Some of the classic systemic choline is blocked from reaching the Management
symptoms of the disorder include dif- post-synaptic receptors.13 Subsequently, There are four easy clinical tests for
ficulty in swallowing (dysphagia) and an enzyme, acetylcholinesterase, MG that can be performed in the
slurred speech.2-7 Ocular signs and degrades acetylcholine and the com- office. In the sleep test, the patient is
symptoms include intermittent pupil ponent parts are sequestered into the asked to rest with eyes closed for 20
sparing ophthalmoparesis and diplop- presynaptic membrane to formulate minutes. As the acetylcholine builds
ia, ptosis of the eyelid, and the pathog- new acetylcholine for the next action up in the presynaptic membranes, pre-
nomonic Cogan’s lid twitch (over- potential. This leads to an inability to existing weaknesses will improve for a
shooting of the affected eyelid on move muscles, rapid fatiguing and loss short time. In another test, the patient
upgaze with a final ptotic resting posi- of stamina.13 is asked to look up (for ocular MG) or
tion after prolonged fixation in down A subset of myasthenia gravis to keep the arms up (for general MG).
gaze).2-9 patients are seronegative for anti- As patients fatigue, they become
Generalized myasthenia gravis will acetylcholine receptor (anti-AChR) unable to continue and the eyelid or
develop in more than 50% of patients antibodies.12 They are referred to as arms will drift down. Additionally for
presenting with ocular myasthenia, typi- seronegative myasthenics.12 These ocular MG, the patient can be asked to
cally within two years.2,7 The conversion patients are instead seropositive for squeeze eyes closed, or, for systemic
rate to the generalized form is as high as antibodies against the muscle-specific MG, to squeeze the examiner’s finger.
90% within three years of the onset of kinase (anti-MuSK-positive).12 Just If they lack strength or they fatigue
ocular symptoms.2,7,10 If MG affects only because an individual is seronegative quickly, it becomes apparent that MG
the eye for four years, it rarely will after one test does not mean they will may be involved. For patients with
progress to systemic involvement. remain so.12 In one study, 15.2% of ptosis or ophthalmoplegia, the ice-
Late-onset MG is a phenomenon of patients initially determined to be pack test can be employed. In this sit-
elderly men that is often misdiag- seronegative became seropositive 12 uation, a bag of crushed ice covered in
nosed.3 While the involvement of months later, yielding an ultimate a towel is placed over the affected eye,
oropharyngeal musculature has been seronegativity rate of 8.2%.14 The clas- with eyelid closed, for two minutes.
well described as symptoms of dyspha- sification of seronegative MG is Lowering the temperature slows the
OCULOSYSTEMIC DISEASE
action of acetylcholinesterase, allowing ods lasting at least two years in approx- atypical course of myasthenia gravis. Proc West
Pharmacol Soc 2007;50:140-2.
acetylcholine a longer duration in the imately 70% of patients.19 Thym- 3. Montero-Odasso M. Dysphonia as first symptom of
synaptic cleft and a greater opportuni- ectomy may be required in selected late-onset myasthenia gravis. J Gen Intern Med
ty to interact with post-synaptic recep- cases.20 Age, gender, onset of symp- 2006;21(6):C4-6.
4. Ferrero S, Esposito F, Biamonti M, et al. Myasthenia
tors with a subsequent improvement in toms, the duration of the disease, the gravis during pregnancy. Expert Rev Neurother
function. response to medicinal preparations and 2008;8(6):979-88.
The abovementioned in-office tests the presence of thymoma help to 5. Ortiz S, Borchert M. Long-term outcomes of pedi-
atric ocular myasthenia gravis. Ophthalmol 2008;
greatly increase the index of suspicion determine whether thymectomy is 115(7):1245-1248.
for MG. Definitive testing is necessary appropriate.21 Owing to improved 6. Juel VC, Massey JM. Myasthenia gravis. Orphanet J
to make a conclusive diagnosis. This diagnostic testing and immunothera- Rare Dis 2007;2(1):44.
7. Kupersmith MJ, Latkany R, Homel P. Development
involves pharmacologic testing with py, the prognosis for MG is favorable of generalized disease at 2 years in patients with ocular
edrophonium chloride (Tensilon™, with less than 5% mortality and a myasthenia gravis. Arch Neurol 2003;60(2):243-8.
ICN, Costa Mesa, CA) that elicits nearly normal life expectancy.6 8. Kusner LL, Puwanant A, Kaminski HJ. Ocular myas-
thenia: diagnosis, treatment, and pathogenesis.
unequivocal improvement in strength Neurologist 2006;12(5):231-9.
and function, electrophysiological test- Clinical Pearls 9. Kusuhara T, Nakajima M, Imamura A. Ocular myas-
ing with repetitive nerve stimulation • Myasthenia gravis never affects the thenia gravis associated with euthyroid ophthalmopa-
thy. Muscle Nerve 2003;28(6):764-6.
and/or single-fiber electromyography pupil. If there is ptosis and ophthalmo- 10. Monsul NT, Patwa HS, Knorr AM, et al. The effect
(SFEMG) that demonstrates a pri- plegia, and the pupil is affected, MG is of prednisone on the progression from ocular to gener-
mary postsynaptic neuromuscular junc- not the cause. alized myasthenia gravis. J Neurol Sci 2004;217(2):
131-3.
tional disorder and serologic assay of • Eaton-Lambert myasthenic syn- 11. Yaguchi H, Takei A, Honma S, et al. Dropped head
acetylcholine receptor (AChR) or mus- drome resembles late-onset MG; how- sign as the only symptom of myasthenia gravis. Intern
cle-specific tyrosine kinase (MuSK) ever, its pathophysiology occurs in the Med 2007;46(11):743-5.
12. Szczeklik W, Jankowski M, Wegrzyn W, et al.
antibodies.5,12 presynaptic endplate, not the post Acute respiratory failure in patients with Guillain-Barré
Once MG has been confirmed, addi- synaptic. Although it produces systemic syndrome and myasthenic crisis treated with plasma-
tional laboratory work should include a signs similar to those of MG, Eaton- pheresis in the intensive care unit. Pol Arch Med Wewn
2008;118(4):239-42.
computed tomography scan (CT) of the Lambert patients do not fatigue upon 13. Cole RN, Reddel SW, Gervásio OL, et al. Anti-
chest, antinuclear antibody testing working, rarely exhibit eye signs and MuSK patient antibodies disrupt the mouse neuromus-
(ANA), a rheumatoid factor test (RF) have a pathology linked to paraneoplas- cular junction. Ann Neurol 2008;63(6):782-9.
14. Chan KH, Lachance DH, Harper CM, et al.
and a thyroid panel (T3, T4, TSH), tic (small-cell lung carcinoma and oth- Frequency of seronegativity in adult-acquired generalized
since it has been associated with other ers) or autoimmune systemic disease, myasthenia gravis. Muscle Nerve 2007;36(5):651-8.
autoimmune diseases.17 making this element an essential com- 15. Tormoehlen LM, Pascuzzi RM. Thymoma, myas-
thenia gravis, and other paraneoplastic syndromes
Treatment must be individualized ponent of the laboratory work in suspi- Hematol Oncol Clin North Am 2008;22(3):509-26.
for each patient, and may include cious cases. 16. Lee BW, Ihm SH, Shin HS, et al. Malignant thymo-
cholinesterase inhibitors (Mestinon™, • MG becomes unpredictable in ma associated with myasthenia gravis, Graves’ dis-
ease, and SIADH. Intern Med 2008;47(11):1009-12.
pyridostigmine, Valeant, Aliso Viejo, pregnant women, with life-threatening 17. Burden G, Bryant SA. Myasthenia gravis. In:
CA) and immune modulation with sequelae possible. These patients Burden G, Bryant SA. Laboratory and Radiologic Tests
corticosteroids, azathioprine, cyclo- require frequent and regular progress for Primary Eye Care. Boston: Buterworth-Heinemann,
1997, p. 30.
sporine and mycophenolate mofetil.6,18 evaluations. 18. Barton JJ, Fouladvand M. Ocular aspects of myas-
Rapid, temporary improvement may • The ice-pack test works exception- thenia gravis. Semin Neurol 2000;20(1):7-20.
be achieved for myasthenic crises and ally well with ptosis as the presenting 19. Kupersmith MJ, Ying G. Ocular motor dysfunction
and ptosis in ocular myasthenia gravis: Effects of treat-
episodic exacerbations with either weakness, but it is less effective and ment. Br J Ophthalmol 2005; 89(10):1330-4.
steroids, plasma exchange (PEX) or diagnostic when ophthalmoparesis is 20. Mahadeva B, Phillips LH 2nd, Juel VC.
intravenous immunoglobulin (IVIg).6 the presenting sign. Autoimmune disorders of neuromuscular transmission.
Semin Neurol 2008;28(2):212-27.
One report demonstrated that pred- • The late great Dr. Larry Gray used 21. Cardone A, Congedo E, Aceto P, et al.
nisone significantly lowered the con- to remind us of the testing for MG by Perioperative evaluation of myasthenia gravis. Ann Ital
version rate from pure ocular MG to saying, “Sleep ’em, tease ’em, squeeze Chir 2007;78(5):359-65.
common cause of immunologic inflam- Romberg’s sign is a disequilibrium precisely certain of the etiology of MS.
mation that initiates the process of associated with cerebellar dysfunction; The disease seems to develop in
demyelination, the loss of insulating it causes patients to be unable to main- patients who demonstrate genetic sus-
ceptibility, although there are likely sev-
eral environmental triggers that play a
role in its pathogenesis. Based upon
animal models of experimental autoim-
mune encephalomyelitis, MS appears
to involve autoantigens within the CNS
that recruit microglial cells and macro-
phages; in turn, these cells activate
cytokines (e.g., interferon-gamma and
tumor necrosis factor alpha), comple-
ment and other immunomodulatory
regulators to spur an inflammatory
reaction.2 This response specifically tar-
gets oligodendrocytes and results in
myelin disruption. When the myelin
sheath becomes damaged, saltatory
This MS patient had a history of optic neuritis in his right eye several years before being diagnosed. nerve conduction is disturbed, resulting
in motor impairment. There is also evi-
myelin sheath about the body’s nerve tain balance when their eyes are closed.5 dence that a smaller subset of MS
axons.1,2 MS affects approximately From an ophthalmic perspective, the patients may have a primary disorder
400,000 Americans and nearly 2 million most frequently encountered ocular within the oligodendrocytes that is
people worldwide.2 The classic MS manifestation of MS is optic neuritis reminiscent of virus or toxin-induced
patient is a white female in her child- (ON). ON is often the initial present- demyelination.11
bearing years; women between the ages ing sign of MS as well.6-8 Internuclear The characteristic pathology of MS
of 20 and 40 have a twofold greater inci- ophthalmoplegia (INO) has a well doc- involves multicentric, multiphasic CNS
dence than men, and white individuals umented association with MS. In fact, a inflammation and demyelination.2
(particularly those of northern Euro- higher percentage of young female There is a predilection for specific areas
pean descent) are especially vulnerable.2 patients experiencing INO eventually of the nervous system including the
MS tends to present insidiously and develop MS than those who have suf- optic nerve and periventricular white
produces a wide variety of neurological fered an episode of optic neuritis.9,10 matter of the cerebellum, brain stem,
complaints, but the most common ini- Other ocular manifestations associated basal ganglia and spinal cord. On aver-
tial symptoms appear to be weakness in with MS include acquired pendular age, patients experience clinical relapses
one or more limbs, parasthesias, optic nystagmus, central vestibular nystag- every one to two years during the so-
neuritis (demyelinating optic neuropa- mus (i.e., downbeat and upbeat), peri- called relapsing-remitting phase of the
thy), diplopia and vertigo.2 Patients odic alternating nystagmus, supranu- disease, although studies using serial
may also experience classic dysfunc- clear gaze palsies (i.e., dorsal midbrain magnetic resonance imaging (MRI)
tions associated with demyelinating syndrome) and isolated ocular motor suggest that inflammatory lesions are
disease, including Uhthoff ’s phenome- abnormalities (i.e., abducens palsy).9 practically continuous throughout this
non, L’Hermitte’s phenomenon and Pars planitis also demonstrates a rela- period.12 In later stages of MS, active
Romberg’s sign. Uhthoff ’s phenome- tively high association with MS.10 inflammation appears to diminish,
non is characterized by impairment of although disability often continues to
vision with increased body temperature. Pathophysiology advance, suggestive of a more chronic,
It is often encountered when taking a MS is defined by recurrent bouts of degenerative process.12,13 Speculation
hot shower or during vigorous exercise.3 central nervous system (CNS) inflam- exists that consecutive tissue injury in
L’hermitte’s phenomenon is noted as a mation that results in damage to both MS ultimately exceeds a critical thresh-
radiating neck pain (sometimes the myelin sheath surrounding axons old beyond which the nervous system
described as an electric shock wave) and the axons themselves.1-10 As with can no longer compensate. At this point
upon flexure of the cervical vertebrae.4 most autoimmune disorders, no one is the disease becomes primarily degener-
OCULOSYSTEMIC DISEASE
ative in nature and is referred to as sec- two or more MRI lesions consistent tonic spasms.21
ondary progressive MS.2 with MS plus positive CSF finding or Ongoing disease-modifying therapy
second clinical attack; consists primarily of immunomodula-
Management • One attack with objective clinical tory agents. The major drugs used in
Four decades ago, Schumacher and evidence of at least two lesions plus dis- the United States include interferon
associates suggested that the core diag- semination in time on MRI or second beta-1b (Betaseron® subcutaneous;
nosis of MS involved CNS lesions dis- clinical attack; Schering, Berlin) and interferon beta-
seminated in space and time, as well as • One attack with objective clinical 1a (Avonex® intramuscular; Biogen,
the elimination of alternative diag- evidence of one lesion, plus dissemina- Cambridge, MA; Rebif® subcutaneous;
noses.14 Despite the numerous proce- tion in space shown on MRI or two or Serono, Geneva). Also widely used is
dures that have been added to our diag- more MRI lesions consistent with MS glatiramer acetate (Copaxone® subcu-
nostic armamentarium since that time, plus positive CSF finding and dissemi- taneous; Teva; Petach Tikva, Israel). In
there exists today no single, absolute nation in time shown on MRI or sec- randomized, placebo-controlled trials,
pathognomonic criterion for MS. The ond clinical attack; all of these medications were shown to
diagnosis ultimately must be a clinical • Insidious neurologic progression decrease the rate of clinical relapses by
decision, based upon the presenting suggestive of MS plus one year of dis- about 30–40%, and they also reduced
signs and symptoms, as well as the sup- ease progression determined retrospec- the number of new lesions appearing on
porting laboratory and radiographic tively or prospectively and two of the magnetic resonance imaging.22-25
findings. following: positive brain MRI result Mitoxantrone (Novantrone® intra-
Serologic testing of the cerebral (nine T2 lesions or at least four T2 venous infusion; Serono USA,
spinal fluid is often helpful in a diagno- lesions with positive Visual Evoked Rockland, MA) is a newer immuno-
sis of MS. Oligoclonal IgG bands have Potential), positive spinal cord MRI suppressant medication that has
been found to be prevalent in patients result with two focal T2 lesions, and demonstrated efficacy in progressive
suffering from MS.15 Moreover, MRI is positive CSF findings. MS. It is typically administered every
perhaps the single greatest diagnostic Treatment for patients with MS three months, although it may be given
and prognostic tool in the management involves management of acute attacks monthly for the first few doses to
of MS today. Clinically definite MS and symptoms and prevention of patients with very active disease.
demonstrates multiple periventricular relapses and progression. In this regard, Unfortunately, side effects and potential
and discrete cerebral hemisphere white it is crucial to initiate disease-modify- toxicities, including cardiac toxicity,
matter lesions known as plaques; these ing therapy as soon as possible. Current limit the use of Novantrone® to
are sometimes referred to as “unidenti- therapies are aimed at eliminating the patients with secondary progressive MS
fied bright objects” or “UBOs” because immune dysfunction and resultant neu- or very active relapsing-remitting MS.26
of their appearance on MRI. ral damage with the goal of preventing
In 2001, new recommendations the long-term risk of clinically signifi- Clinical Pearls
regarding diagnostic criteria for MS cant disability. • Certain clinical and/or demo-
were published by an international Acute attacks (and those resulting in graphic risk factors such as age of onset,
panel of experts.16-18 The “McDonald ON) are usually treated with intra- gender, CNS involvement, course of
criteria” allowed for MRI evidence in venous methylprednisolone 1000 mg disease and attack frequency can aid cli-
the diagnosis of MS in patients who daily for three days, followed by a taper- nicians in determining the prognosis
experienced a single acute clinical ing dose of oral prednisone over several for a patient with MS. Individuals with
episode.16 Subsequent revisions of these weeks. Although protocols vary, this is a favorable prognosis fit the following
McDonald criteria were published in the most widely used regimen accord- profile: age of onset younger than 40
2005, and updated further by Swanton ing to current sources.19,20 In addition, years, female, optic neuritis or other
and associates in 2006.17,18 Today, most 4-aminopyridine and 3,4-diaminopyri- sensory symptoms at onset, relapsing/
clinicians rely on the following to make dine may prove useful for the sympto- remitting disease course and a low
a diagnosis of MS: matic treatment of some multiple scle- attack frequency. Individuals with an
• At least two attacks with objective rosis patients. Pemoline may be an unfavorable prognosis are those whose
clinical evidence of at least two lesions; alternative to amantadine for the con- age of onset is older than 40 years, male,
• At least two attacks with objective trol of fatigue, and acetazolamide may have motor or cerebellar symptoms,
clinical evidence of one lesion plus dis- be an alternative to carbamazepine and neurologic findings at onset, a progres-
semination in space shown on MRI or phenytoin for the treatment of painful sive course of the disease and a high
number of attacks. Premyelinating oligodendrocytes in chronic lesions of and seventh decades of life represent
multiple sclerosis. N Engl J Med 2002;346(3):165-73.
• The association between optic neu- 14. Schumacher GA, Beebe GW, Kibler RF, et al.
age peaks of incidence, with a slight
ritis and MS has been previously Problems of experimental trials of therapy in multiple preponderance for women.3 The natural
demonstrated and is well documented. sclerosis: Report by the panel on the evaluation of history of the disease remains poorly
experimental trials of therapy in multiple sclerosis. Ann
However, a number of other types of NY Acad Sci 1965;122:552-68.
defined.1-4 In fact, the ocular aspects of
demyelinating disorders have been asso- 15. Harrington MG, Kennedy PG. The clinical use of the disease may remit or improve spon-
ciated with optic neuritis. These include cerebrospinal fluid studies in demyelinating neurological taneously.3 The ocular conditions char-
diseases. Postgrad Med J 1987;63(743):735-40.
acute transverse myelitis, Gullain-Barré 16. McDonald WI, Compston A, Edan G, et al.
acteristic of the disease may exist in the
syndrome, Devic’s neuromyelitis optica, Recommended diagnostic criteria for multiple sclerosis:
Charcot-Marie-Tooth syndrome, multi- guidelines from the International Panel on the diagnosis
of multiple sclerosis. Ann Neurol 2001;50(1):121-7.
focal demyelinating neuropathy and 17. Polman CH, Reingold SC, Edan G, et al. Diagnostic
acute disseminated encephalomyelitis. criteria for multiple sclerosis: 2005 revisions to the
• At one time, when a patient pre- “McDonald Criteria.” Ann Neurol 2005;58(6):840-6.
18. Swanton JK, Fernando K, Dalton CM, et al.
sented with an acute optic neuropathy Modification of MRI criteria for multiple sclerosis in
or INO suggestive of demyelinating patients with clinically isolated syndromes. J Neurol
disease, there was no great hurry to Neurosurg Psych 2006;77(7):830-3.
19. Murray TJ. Diagnosis and treatment of multiple
confirm a diagnosis of MS because no sclerosis. BMJ 2006;332(7540):525-7.
effective treatments were available. 20. Beck RW, Cleary PA. Optic neuritis treatment trial.
Today there are a number of medica- One-year follow-up results. Arch Ophthalmol
1993;111(6):773-5.
tions that reduce the incidence and 21. Noseworthy JH. Clinical trials in multiple sclerosis. Graves' Disease is evident in this patient with
recurrence of neurological deficits and Curr Opin Neurol Neurosurg 1993;6(2):209-15.
thyroid ophthalmopathy.
impairment and delay the onset of 22. The IFNB Multiple Sclerosis Study Group,
University of British Columbia MS/MRI Analysis Group.
clinical MS. Hence, if MS is suspected, Interferon beta-1b in the treatment of multiple sclerosis:
absence of clinical or biochemical evi-
testing should be conducted immedi- Final outcome of the randomized, controlled trial. dence of thyroid dysfunction.2,3 When
ately to confirm the diagnosis. Neurol 1995;45(7):1277-85. the systemic and ocular condition exist
23. Galetta SL. The controlled high risk Avonex multi-
ple sclerosis trial (CHAMPS Study). J Neuroophthalmol
together, they may follow completely
1. Peterson LK, Fujinami RS. Inflammation, demyelina- 2001;21(4):292-5. different clinical courses.2-6
tion, neurodegeneration and neuroprotection in the 24. Johnson KP, Brooks BR, Cohen JA, et al. The hallmark sign of TO is bilateral,
pathogenesis of multiple sclerosis. J Neuroimmunol Copolymer 1 reduces the relapse rate and improves
2007;184(1-2):37-44. disability in relapsing-remitting multiple sclerosis:
non-pulsatile proptosis secondary to
2. Inglese M. Multiple sclerosis: New insights and Results of a phase III multicenter, double-blind, place- tendon sparing extraocular muscle
trends. AJNR Am J Neuroradiol 2006;27(5):954-7. bo-controlled trial. Neurol 1995;45(7):1268-76. enlargement.1-4 Other important find-
3. Stutzer P, Kesselring J. Wilhelm Uhthoff: A phenom- 25. PRISMS Study Group. Randomised double-blind
enon 1853 to 1927. Int MS J 2008;15(3):90-3. placebo-controlled study of interferon beta-1a in relaps-
ings include impaired ocular motility
4. Boneschi FM, Colombo B, Annovazzi P, et al. ing/remitting multiple sclerosis. Lancet 1998;352(9139): and ophthalmoplegia with resultant
Lifetime and actual prevalence of pain and headache in 1498-504. diplopia, firm resistance to globe
multiple sclerosis. Mult Scler 2008;14(4):514-21. 26. Avasarala JR, Cross AH, Clifford DB, et al. Rapid
5. Pearce JM. Romberg and his sign. Eur Neurol onset mitoxantrone-induced cardiotoxicity in secondary
retropulsion, eyelid retraction, poor
2005;53(4):210-3. progressive multiple sclerosis. Mult Scler 2003;9(1):59-62. upper eyelid tracking upon downgaze
6. Chan JW. Optic neuritis in multiple sclerosis. Ocul (Von Graefe’s sign), variable diplopia,
Immunol Inflamm 2002;10(3):161-86.
7. Soderstrom M. Optic neuritis and multiple sclerosis. possibly impaired visual acuity and
Acta Ophthalmol Scand 2001;79(3):223-7. THYROID OPHTHALMOPATHY visual field defects, sight loss secondary
8. Pirko I, Blauwet LK, Lesnick TG, et al. The natural to corneal exposure-related keratopathy
history of recurrent optic neuritis. Arch Neurol
2004;61(9):1401-5. Signs and Symptoms or compressive optic neuropathy.7,8
9. Rucker JC. Efferent visual dysfunction from multiple Graves’ disease, Graves orbitopathy, Thyroid-associated dermopathy
sclerosis. Int Ophthalmol Clin 2007;47(4):1-13. dysthyroid orbitopathy, thyroid eye dis- with fluid infiltration in the lower
10. Chen L, Gordon LK. Ocular manifestations of multi-
ple sclerosis. Curr Opin Ophthalmol 2005;16(5):315-20. ease and thyroid ophthalmopathy (TO) extremities, particularly the pretibial
11. Lucchinetti CF, Brück W, Rodriguez M, et al. are all synonymous terms connoting an area of the leg (pretibial myxedema),
Distinct patterns of multiple sclerosis pathology indi- autoimmune disorder characterized by the dorsum of the foot, rarely the hand,
cates heterogeneity on pathogenesis. Brain Pathol
1996;6(3):259-74. multiple systemic manifestations.1,2 elbow, upper arm and forearm, and
12. Confavreux C, Vukusic S. Accumulation of irre- Thyroid ophthalmopathy manifests acropachy (clubbing of the fingers and
versible disability in multiple sclerosis: from epidemiolo- in approximately 50% of patients with toes) almost always occurs in advanced
gy to treatment. Clin Neurol Neurosurg 2006;108(3):
327-32. systemic thyroid dysfunction with stages of systemic thyroid disease.5,6
13. Chang A, Tourtellotte WW, Rudick R, et al. advanced effects in 3–5%.3 The fifth These two indicators often occur in the
OCULOSYSTEMIC DISEASE
presence of progressing ophthalmopa- trate orbital tissues, further kindling the because ophthalmopathy can develop in
thy.5 The curiosity of thyroid disease is cascade of inflammation.9,10 Finally, the setting of an underactive, hyperactive
its often unpredictable nature. As an although originally thought to repre- or normally functioning thyroid gland,
example, dermopathy has been sent a separate pathway for inflamma- contingencies for treating glandular mal-
observed in many cases without any tion, antibodies that develop against the function and eye signs and symptoms
clinical ophthalmopathy.5 extraocular muscles are now considered must be developed separately.1-4,7,17-25
a secondary consequence of global Laboratory testing should include
Pathophysiology extraocular muscle inflammation.9 assays for the levels of triidothyronine
The etiology of the disorder is mul- Thyroglobulin (Tg) may also be (T3), thyroxine (T4), thyroid stimulat-
tifactorial and secondary to newly dis- involved in the pathogenesis of TO.13,14 ing hormone (TSH), thyroid peroxi-
covered heritable abnormalities that Following its release from the cytokine dase antibodies, thyroglobin antibodies,
interfere with immune regulation.1 Not stimulated thyroid, Tg may have the thyrotropin receptor antibodies and
all of the mechanisms responsible for ability to elicit autoimmune aggression thyroid stimulating immunoglobulins.2,3
the systemic and/or ocular manifesta- in orbital tissues and extraocular mus- Ultrasonography can be used to assess
tions are understood.2 Research regard- cles by becoming complexed with gly- the condition of the extraocular mus-
ing the clinical manifestations of thy- cosaminoglycans, infiltrating the tissues cles, and computed tomography (CT) is
roid ophthalmopathy traditionally and then serving as a binding site for generally considered the accepted
point to a combination of increased the other previously mentioned modality. Magnetic resonance imaging
orbital fat and extraocular muscle vol- cytokines.13,14 Previously viewed as the (MRI) may be used for those requiring
ume within the orbital space.1,2,9-12 TO is main mechanism of pathogenesis, Tg a detailed view of the soft tissues of the
a slowly progressive disease in which a has recently been confirmed by research entire orbit.18 Monitoring of proptosis
malfunctioning immune system acti- as playing a secondary role.13 should be done either with an exoph-
vates thyrotropin receptor-specific T- Environmental triggers, such as thalmometer or photographs.
cells and B cells.11 This activation pro- smoking, can also induce or hasten Resultant proptosis may require
duces autoantibodies.10 Orbital ophthalmopathy.3,15 Because smoking is monitoring only. Any signs and symp-
fibroblasts residing within orbital tis- a modifiable risk factor, it must be toms associated with ocular surface
sues succumb to autoimmune attack included in the historical questioning compromise can be managed with effi-
when these antibodies bind both to and then approached in management. cient hydration.25,26 Artificial tear solu-
their thyrotropin receptors (TSHr) and Hashimoto’s autoimmune thyroiditis tions and ointments may remedy most
insulin-like growth factor-1 (IGF-1) (HAT) is the most common cause of symptoms.25,26 Punctual occlusion can
receptors.9-12 It appears that orbital thyroid diseases in children and adoles- be used to retard drainage as well.
fibroblasts act as sentinel cells, initiating cents.16 It is also is the most common Patients with increased symptoms upon
lymphocyte recruitment and tissue cause of acquired hypothyroidism with waking may have lagophthalmos. In
remodeling.6 Evidence suggests that or without goiter.16 It is capable of these instances, they should be coun-
when the autoantibodies bind to the inducing the orbital changes consistent seled to use a blindfold to create an
thyrotropin receptor sites, they stimu- with thyroid orbitopathy.16 enclosed, moist environment and pre-
late a subset of these cells to undergo vent exposure-based corneal abrasion.
adipogenesis, thus increasing orbital Management In the most severe cases, moisture
adipose tissue volume.9,10 Auto- Thyroid cancer should be considered chambers can be created for waking
antibodies that bind to the insulin-like when examining patients with suspect- hours by affixing face-conforming plas-
growth factor-1 receptors appear to ed TO.10 Prognosis for the disease, tic barriers to the temples of the
impact pathogenesis through recruit- when diagnosed promptly, is excellent patient’s spectacles. Affixed Fresnel or
ment and activation of additional T- in the long term,with low rates of mor- ground-in prisms may improve fusion
cells and by upregulating the produc- tality.12 Unlike other cancers of the in patients with ophthalmoparesis and
tion of hyaluronan (hyaluronic acid), a head and neck, it tends toward delayed diplopia.26 In rare instances, congestion
cytokine that plays a key role in the metastasis to regional lymph nodes.17 of the orbit can lead to raised intraocu-
development of inflammation and Since the hallmark sign of TO is a lar pressure. Here, topical hypotensives
increased orbital tissue swelling.9,10 bilateral, symmetrical, proptotic appear- may be appropriate.
Simultaneously, the process stimulates an ance, laboratory testing and imaging is Clinical trials with oral antihista-
overproduction of thyroid hormones.9-12 indicated to understand the potential mine and anti-leukotriene prepara-
Activated T-cells continue to infil- etiology in suspicious cases.18 However, tions, traditionally used in treating
nasal itching, rhinorrhea and conges- consensus and standardization, with a orbits, making them appear proptotic.
tion, have demonstrated some effec- varying quality of published reports.24,27 Checking old photographs of patients
tiveness for patients with mild-to- At best, radiation therapy offers an to chronicle their habitual appearance
moderate thyroid eye disease and option for patients with extraocular is a helpful tool for determining base-
orbital congestion.19 A six-week course motility impairment; however, mixed line appearance.
of oral cetirizine (10mg q.a.m.) and results have been presented in clinical • Thyroid ophthalmopathy is gen-
oral montelukast (10mg q.p.m.) in a trials, indicating that proptosis, eyelid erally symmetric and bilateral. A meas-
series of patients with significant oph- retraction and soft tissue changes may urement difference of 6mm or more
thalmopathy yielded subjective improve- not improve with radiation treat- between the eyes is ominous and not
ment in tearing, dryness and itching in ment.5,24,27 Given the risk of radiation consistent with TO.
50% of subjects compared to controls, retinopathy vs. the controversial gains • Cases involving thyroid dysfunc-
although it was less effective for against symptoms, patients should be tion should be referred to an endocri-
diplopia and proptosis.19 appropriately educated before consider- nologist.
Oral and intravenous steroids have ing this solution.24 1. Kim N, Hatton MP. The role of genetics in Graves’
been demonstrated as successful thera- Orbital decompression by trans- disease and thyroid orbitopathy. Semin Ophthalmol
pies for cases of moderate-to-severe palpebral fat removal is a proven, reli- 2008;23(1):67-72.
2. Sergott RC, Glaser JS. Graves’ ophthalmopathy. A
ophthalmopathy..20,21,26 Work has shown able, effective and safe method of clinical and immunologic review. Surv Ophthalmol
that blocking the CD-20 receptor on B relieving the compressive complica- 1981;26(1):1-21.
lymphocytes has significantly affected tions of TO. The results were first 3. Wiersinga WM, Bartalena L. Epidemiology and pre-
vention of Graves’ ophthalmopathy. Thyroid
the clinical course of TO, resulting in described in 1988, and the procedure 2002;12(10):855-60.
rapid reduction of inflammation and has developed a track record for lasting 4. Ben Simon GJ, Syed HM, Douglas R, et al.
proptosis.20 results, improvement in visual function Extraocular muscle enlargement with tendon involve-
ment in thyroid-associated orbitopathy. Am J
Experimental use of infliximab (anti- and development of patient well-being, Ophthalmol 2004;137(6):1145-7.
tumor necrosis factor alpha) has also with benefits outweighing risk.7 5. Fatourechi V, Bartley GB, Eghbali-Fatourechi GZ, et
been investigated in TO patients sec- al. Graves’ dermopathy and acropachy are markers of
severe Graves’ ophthalmopathy. Thyroid 2003;13(12):
ondary to its ability to decrease inflam- Clinical Pearls 1141-4.
mation.22 Although the option is a rea- • Thyroid eye disease can occur in 6. Hasani-Ranjbar S, Mohajeri-Tehrani MR. Localized
sonable alternative to surgical the presence of hyperthyroid, hypothy- myxedema of the toe: A rare presentation of graves’
dermopathy. Arch Iran Med 2008;11(3):326-9.
approaches, the data on this new strat- roid or euthyroid states. Hyperthyroid 7. Richter DF, Stoff A, Olivari N. Transpalpebral decom-
egy is currently limited with respect to is marked by unexplained weight loss, pression of endocrine ophthalmopathy by intraorbital
thyroid eye disease and orbital inflam- nervousness and tachycardia; hypothy- fat removal (Olivari technique): Experience and progres-
sion after more than 3000 operations over 20 years.
matory conditions.22 roidism is marked by intolerance to Plast Reconstr Surg 2007;120(1):109-23.
In cases in which TO is associated cold, premature fatigue and depression. 8. Gaddipati RV, Meyer DR. Eyelid retraction, lid lag,
with an overactive thyroid gland, vari- • The classic “NOSPECS” pneu- lagophthalmos, and von Graefe’s sign quantifying the
eyelid features of Graves’ ophthalmopathy. Ophthalmol
ous antithyroid medications can be monic permits an easy-to-recall system 2008;115(6):1083-8.
employed, with or without the possi- of staging: N=no signs or symptoms, 9. Khoo TK, Bahn RS. Pathogenesis of Graves’ oph-
bility of radioiodine treatment.25,26 O = only signs such as the “stare” or thalmopathy: The role of autoantibodies. Thyroid
2007;17(10):1013-8.
Some indications suggest that the use Von Graefe’s sign but no symptoms, 10. Garrity JA, Bahn RS. Pathogenesis of graves oph-
of radioiodine treatment may worsen S = soft tissue involvement (resistance thalmopathy: implications for prediction, prevention,
ophthalmopathy.3,23,26 A concomitant to retropulsion, conjunctival edema, and treatment. Am J Ophthalmol 2006;142(1):147-53.
11. Prabhakar BS, Bahn RS, Smith TJ. Current per-
course of oral steroids is frequently fullness of the eyelids, injection of the spective on the pathogenesis of Graves’ disease and
used to mitigate this effect.3,23,26 The horizontal recti insertions), P=propto- ophthalmopathy. Endocr Rev 2003;24(6):802-35.
combination of corticosteroid treat- sis, E=extraocular muscle involvement, 12. Karasek M, Lewinski A. Etiopathogenesis of
Graves’ disease. Neuro Endocrinol Lett 2003;24(3-
ment and external beam radiation to C=corneal involvement, S=sight loss. 4):161-6.
the thyroid gland is another effective • The classic Dalrymple’s sign is 13. Lisi S, Botta R, Agretti P, et al. Poorly specific bind-
modality in which multiple mecha- characterized by eye lid retraction and ing of thyroglobulin to orbital fibroblasts from patients
with Graves’ ophthalmopathy. J Endocrinol Invest
nisms can be placated.21 “stare,” Moebius, sign is marked by an 2005;28(5):420-4.
Orbital radiation is a controversial inability to converge, and Gifford’s sign 14. Marinò M, Lisi S, Pinchera A, et al. Glycosa-
local treatment modality for patients is marked by difficulty in everting the minoglycans provide a binding site for thyroglobulin in
orbital tissues of patients with thyroid-associated oph-
with severe thyroid ophthalmopathy.24,27 eyelids. thalmopathy. Thyroid 2003;13(9):851-9.
The literature demonstrates a lack of • Many patients have shallow 15. Zhang Q, Yang YM, Lv XY. Association of Graves’
OCULOSYSTEMIC DISEASE
disease and Graves’ ophthalmopathy with the polymor- Oculocutaneous albinism (OCA), tagmus, strabismus and photophobia,
phisms in promoter and exon 1 of cytotoxic T lympho-
cyte associated antigen-4 gene. J Zhejiang Univ Sci B
also known as oculodermal albinism, is in the setting in which pigmentation
2006;7(11):887-91. a group of inherited defects of melanin of skin and hair is relatively normal.6
16. Lorini R, Gastaldi R, Traggiai C, et al. Hashimoto’s biosynthesis characterized by reduc- Incomplete albinism or albinoidism is
Thyroiditis. Pediatr Endocrinol Rev 2003;1(Suppl
2):S205-S211.
tion in pigmentation of the hair, skin characterized by variable manifesta-
17. Cognetti DM, Pribitkin EA, Keane WM. and eyes.2 The clinical spectrum of tions of the albino condition, owing to
Management of the neck in differentiated thyroid can- OCA ranges from OCA1A, the most a genetic variation.7
cer. Surg Oncol Clin N Am 2008;17(1):157-73.
18. Lennerstrand G, Tian S, Isberg B, et al. Magnetic
severe type, which demonstrates a
resonance imaging and ultrasound measurements of complete lack of melanin production Pathophysiology
extraocular muscles in thyroid-associated ophthal- throughout life, to milder forms such All types of OCA have been estab-
mopathy at different stages of the disease. Acta
Ophthalmol Scand 2007;85(2):192-201.
as OCA1B, OCA2, OCA3 and lished as inherited autosomal recessive
19. Lauer SA, Silkiss RZ, McCormick SA. Oral mon- OCA4, each of which shows some disorders.2 The four genes determined
telukast and cetirizine for thyroid eye disease. Ophthal pigment accumulation over time. The2
to be responsible for the different
Plast Reconstr Surg 2008;24(4):257-61.
20. Salvi M, Vannucchi G, Campi I, et al. New
clinical manifestations of OCA types of the disease are TYR, OCA2,
immunomodulators in the treatment of Graves’ oph- include congenital nystagmus, iris TYRP1 and MATP.2 Because of the
thalmopathy. Ann Endocrinol 2008;69(2):153-6. hypopigmentation and translucency, clinical overlap in forms of albinism,
21. Zoumalan CI, Cockerham KP, Turbin RE, et al.
Efficacy of corticosteroids and external beam radiation
varying degrees of strabismus, reduced molecular techniques must be
in the management of moderate to severe thyroid eye stereoscopic vision, reduced pigmenta- employed to establish a specific sub-
disease. J Neuroophthalmol 2007;27(3):205-14. tion of the retinal pigment epithelium type.2 Studies have shown that ocular
22. Prendiville C, O’Doherty M, Moriarty P, et al. The
use of infliximab in ocular inflammation. Br J
(RPE), foveal hypoplasia, reduced albinism may constitute a clinically
Ophthalmol 2008;92(6):823-5. visual acuity (20/60 to mild presentation of
23. Sisson JC, Schipper MJ, Nelson CC, et al. 20/400), varying refrac- oculocutaneous albi-
Radioiodine therapy and Graves’ ophthalmopathy. J
Nucl Med 2008;49(6):923-30.
tive errors, color vision nism resulting from
24. Bradley EA, Gower EW, Bradley DJ, et al. Orbital impairment and debili- mutations either in the
radiation for graves ophthalmopathy: A report by the tating photophobia.2 TYR (OCA1) or
American Academy of Ophthalmology. Ophthalmol
2008;115(2):398-409.
Patients with OCA OCA2 (P) genes.6 The
25. Modjtahedi SP, Modjtahedi BS, Mansury AM, et al. have a normal lifespan genetic mutation
Pharmacological treatments for thyroid eye disease. with normal develop- responsible for HPS
Drugs 2006;66(13):1685-700.
26. Wiersinga WM. Management of Graves’ ophthal-
ment and fertility.2 External view of ocular albinism. remains unknown.4 The
mopathy. Nat Clin Pract Endocrinol Metab 2007 Some forms of OCA CHS1/LYST gene has
May;3(5):396-404. have systemic associations.3-5 Herman- been associated with Chediak-Higashi
27. Gorman CA, Garrity JA, Fatourechi V, et al. A
prospective, randomized, double-blind, placebo-con-
sky-Pudlak syndrome (HPS), for syndrome.5 Mutations in the OA1
trolled study of orbital radiotherapy for Graves’ ophthal- example, is an autosomal-recessive dis- gene on the short arm of the X chro-
mopathy. Ophthalmol 2001;108(9):1523-34. order characterized by oculocutaneous mosome are known to cause X-linked
albinism, platelet dysfunction and ocular albinism known as the
ALBINISM multisystem tissue lysosomal ceroid Nettleship-Falls variant.8
3,4
deposition. It is most common in the The common denominator of
Signs and Symptoms Puerto Rican population.3 Chediak- decreased vision in patients with
Albinism is a genetic condition Higashi syndrome is a albinism is decreased
associated with defects in melanin pro- rare autosomal recessive foveal volume and macular
duction or storage, causing maldevel- disorder in which hypoplasia.1,9-11 This find-
opment of the visual system and fovea, patients show hypopig- ing is compatible with a
reduced retinal cell numbers and mentation, recurrent infec- reduction or loss of gan-
abnormal routing of ganglion cell tions, mild coagulation glion cell numbers.1,2 This
nerve fibers within the optic chiasm defects and varying neu- is a different process than
and visual pathway.1 The prevalence of rologic problems.5 Ocular albinism - fundus. the one that merely pro-
all forms of albinism varies with esti- Ocular albinism (OA) duces an anatomical lack
mates at approximately one in 17,000 is characterized as a group of genetic of foveal pit, which is not a requirement
persons.2 This suggests that one in 70 disorders presenting with reduced pig- for foveal cone specialization.9,10 New
people carry a gene for albinism in one mentation only of the eye in associa- research suggests that the observation
form or another.2 tion with decreased visual acuity, nys- of no foveal pit be known by the specif-
ic term as fovea plana.9,10 Patients may nase positive OCA, there is activity of Winchester optical, Scranton, PA) or
be fovea plana without the effects of the enzyme, but melanin that is pro- the option for protective UV shields™
foveal hypoplasia, as seen in albinotic duced cannot be sequestered into (Fieldale, VA, CP films) or NOIR
maculopathy.9,10 melanosomes. In tyrosinase-negative shields™ (South Lion, MI, NOIR
Since the foveal region contains the OCA, inactivity of the enzyme pre- medical technologies). Prescribing the
highest cell density in the human reti- vents melanin formation.17,18 maximum correction, especially in
na, a large area of the visual cortex is younger patients, will maximize visual
dedicated to its representation.10,11 In Management acuity and minimize the amblyogenic
cases of both aniridia and albinism, the When a patient with fair skin and effects of large astigmatic or asymmet-
fovea does not properly develop, caus- minimal fundus pigmentation presents ric corrections. In cases of strabismus
ing its corresponding cortical repre- with or without the presence of com- (with or without an accommodative or
sentations to be reduced.1,11 Analysis promised visual acuity, the possibility refractive component) or where visual
reveals that regionally specific decreas- of albinism should be considered.1-11,19 acuity cannot be corrected to the val-
es in grey matter at the occipital poles A complete family history, including ues obtained via laser interferometry,
in patients with albinism corresponds investigation of family photographs, amblyopia must be considered, with an
to the cortical representation of the may help uncover a genetic link previ- appropriate surgical referral or referral
central visual field and correlates to ously not realized. Since albinism has for binocular evaluation and training.
most of the compromises in visual linkage to systemic syndromes, its exis- Surgical results are variable, and unfor-
function.1 Patients with albinism have tunately, because a facet of this disease
additional chiasmal irregularities and induces axons to aberrantly cross in the
alterations in the hemispheric projec- chiasm, visual training may not be
tions.1,11 Misrouting of the fibers at the effective.20,21 The literature confirms
optic chiasm, where the majority of evidence that surgery on the extraocu-
fibers cross to the contralateral side, lar muscles in patients with albinism
produces an abnormal decussating pat- exhibits independent neurologic and
tern.9-11 This reflects the disturbance visual results.20 A positive angle kappa
within the retina controlled in part by seems to be another clinical feature of
the dysfunction of melanin metabo- the disorder. Surgeons must consider
lism.12 It also is the predominant rea- this when planning extraocular muscle
son most of these patients lack true surgery, particularly when preoperative
binocularity and often present with Ocular albinism - fundus. testing indicates the potential for a
some strabismus. binocular outcome.21
Foveal hypoplasia is related to poor tence cannot be dismissed simply In cases in which traditional specta-
fundus pigmentation in the region.13 because the patient reports no clinical cles do not alleviate visual disabilities,
Melanocytes are pigment-producing symptoms. In cases of high suspicion, low vision rehabilitation along with
cells residing primarily in hair follicles, referral for genetic counseling/testing orientation and mobility rehabilitation
the skin and the eyes.13 Pigmentation (tyrosinase hair bulb assay) may be services may provide magnifying
is achieved inside melanocytes when indicated, both for the welfare of the devices (full-field full-diameter micro-
melanin is produced from the amino patient and to understand the risk to scopes, prism half-eye microscopes,
acid tyrosine and sequestered within potential future generations of the stand magnifiers, handheld micro-
specialized organelles known as mela- patient’s family.2,16 scopes, telemicroscopes, telescopes and
nosomes.13 Normal foveal develop- Ocular management for all forms of closed circuit televisions) as well as
ment requires a proper underlying albinism begins with appropriate spec- supportive aides (acetate filters to
substrate; that is, a normally pigment- tacle correction. Consideration includes increase the contrast of printed materi-
ed RPE. The enzyme tyrosinase, a refractive error and protection from als, large print books, enlarged clocks).
type I membrane glycoprotein, plays a the harmful rays of the sun. Spectacle Prescribing practitioners and rehabili-
key role in the initiation of the corrections should be designed consid- tation specialists each have a role in the
melanogenesis process in humans.14-16 ering either sun specific lenses, photo- management of these patients.
Mutations in the human tyrosinase chromic lenses (Transitions, Pinnelas The nystagmus in patients with
gene cause the tyrosinase negative form Park, FL, Transitions Optical Inc.; albinism is often termed “searching
of oculocutaneous albinism.15 In tyrosi- Photogray™, Corning Optical via nystagmus.”22,23 Research supports that
OCULOSYSTEMIC DISEASE
acuity development in these cases is Clinical Pearls 7. Hall AJ, Sesebe T, Lopes Cardozo R, et al. A high-
frequency albinism variant on the gulf coast of Papua.
directly related to the visual sensory • The differential diagnosis for PNG Med J 1981;24(1):35-9.
defects and not the nystagmus.20,22,23 albinism in general includes ocular 8. Rudolph G, Meindl A, Bechmann M, et al. X-linked
ocular albinism (Nettleship-Falls): A novel 29-bp dele-
The nystagmus develops secondary to albinism, albinoidism, the Hermansky-
tion in exon 1. Carrier detection by ophthalmic exami-
the poor ability to stabilize fixation as a Pudlak variant (albinism + bleeding nation and DNA analysis. Graefes Arch Clin Exp
result of the compromised fovea. The disorder), the Chediak-Higashi variant Ophthalmol 2001;239(3):167-72.
9. Izquierdo NJ, Emanuelli A, Izquierdo JC, et al.
characteristics of searching nystagmus (Albinism + susceptibility to infection),
Foveal thickness and macular volume in patients with
include bilaterality, conjugate horizon- Griscelli syndrome (albinism + oculocutaneous albinism. Retina 2007;27(9): 1227-30.
tal uniplanar movements and an accel- immunodeficiency) and Waardenburg 10. Marmor MF, Choi SS, Zawadzki RJ, et al. Visual
insignificance of the foveal pit: Reassessment of foveal
erating slow phase. Unfortunately, no syndrome type II (facial anomalies,
hypoplasia as fovea plana. Arch Ophthalmol
single ocular motor characteristic can heterochromia of the iris, fundus 2008;126(7):907-13.
differentiate a benign form of infan- pigmentation variation and congenital 11. Neveu MM, von dem Hagen E, Morland AB, et al.
The fovea regulates symmetrical development of the
tile/searching nystagmus from one sensorineural deafness).
visual cortex. J Comp Neurol 2008;506(5):791-800.
with an alternate neurological etiology. • Genetic detection in carriers and 12. Schmitz B, Krick C, Käsmann-Kellner B.
Clinicians must therefore consider the obtaining a prenatal diagnosis is plausi- Morphology of the optic chiasm in albinism.
Ophthalmologe 2007;104(8):662-5.
host of clinical features and rule out the ble when a history of the disease is
13. Neveu MM, Holder GE, Sloper JJ, et al. Optic chi-
need for neurologic consultation.22,23 identified in the family line. asm formation in humans is independent of foveal
Patients with OCA are especially • Albinoidism or ocular albinism development. Eur J Neurosci 2005;22(7):1825-9.
14. Goding CR. Melanocytes: the new black. Int J
vulnerable to the harmful rays of the may be present in patients with normal
Biochem Cell Biol 2007;39(2):275-9.
sun because they lack protective mela- visual acuity who possess the complaint 15. Schallreuter KU, Kothari S, Chavan B, et al.
nin.1,11,24 This puts them at risk for of photophobia. In these cases, the Regulation of melanogenesis—controversies and new
concepts. Exp Dermatol 2008;17(5):395-404.
developing skin lesions that have both patient should be questioned regarding
16. Popescu CI, Paduraru C, Dwek RA, et al. Soluble
cosmetic and systemic health implica- the pigmentation and tanning status of tyrosinase is an endoplasmic reticulum (ER)–associated
tions and that increase their risk for family members. degradation substrate retained in the ER by calreticulin
and BiP/GRP78 and not calnexin. J Biol Chem
developing skin cancers.5 Patients with • Strabismus cases undergoing sur-
2005;280(14):13833-40.
any form of albinism must have regu- gical correction have a poor prognosis 17. Chaki M, Mukhopadhyay A, Chatterjee S, et al.
lar skin evaluations and must be because of the dysfunctional hard- Higher prevalence of OCA1 in an ethnic group of east-
ern India is due to a founder mutation in the tyrosinase
informed about the need for strict and wiring (mal-decussating fibers).
gene. Mol Vis 2005;11(7):531-4.
consistent sun protection strategies.1,24 • Medications with antiplatelet 18. Francis E, Wang N, Parag H, et al. Tyrosinase mat-
Work is underway to develop a foveal properties can produce significant ill uration and oligomerization in the endoplasmic reticu-
lum require a melanocyte-specific factor. J Biol Chem
hypoplasia grading system using optical effects on HPS patients and should be
2003;278(28):25607-17.
coherence tomography (OCT).25 The avoided. 19. Kutzbach BR, Summers CG, Holleschau AM, et al.
same group is undertaking the task of • Patients with extremely blond Neurodevelopment in children with albinism.
Ophthalmol 2008;115(10):1805-8,
attempting to correlate visual acuity to fundus may be misdiagnosed with
20. Hertle RW, Anninger W, Yang D, et al. Effects of
iris transillumination, macular trans- albinism. Patients with albinism will extraocular muscle surgery on 15 patients with oculo-
parency and foveal hypoplasia in young have reduced acuity and nystagmus. cutaneous albinism (OCA) and infantile nystagmus syn-
drome (INS). Am J Ophthalmol 2004;138(6):978-87.
albinism patients.25 This could provide
1. von dem Hagen EA, Houston GC, Hoffmann MB, et 21. Merrill KS, Lavoie JD, King RA, et al. Positive angle
patients and guardians with valuable al. Retinal abnormalities in human albinism translate into kappa in albinism. J AAPOS 2004;8(3):237-9.
prognostic information. a reduction of grey matter in the occipital cortex. Eur J 22. Weiss AH, Kelly JP. Acuity development in infantile
Neurosci 2005;22(10):2475-80. nystagmus. Invest Ophthalmol Vis Sci 2007;48(9):
The traditional treatment for
2. Grønskov K, Ek J, Brondum-Nielsen K. 4093-9.
Chediak-Higashi syndrome is a bone Oculocutaneous albinism. Orphanet J Rare Dis 23. Abadi RV, Bjerre A. Motor and sensory character-
marrow transplant to remedy the 2007;2(11):43. istics of infantile nystagmus. Br J Ophthalmol
3. Feliciano NZ, Rivera E, Agrait E, et al. Hermansky- 2002;86(10):1152-60.
hematologic and immune defects.5
Pudlak syndrome: dental management considerations. 24. Lund PM, Taylor JS. Lack of adequate sun protec-
Unfortunately, nothing is currently J Dent Child (Chic) 2006;73(1):51-6. tion for children with oculocutaneous albinism in South
available to alter the neurologic prob- 4. Iannello S, Fabbri G, Bosco P, et al. A clinical variant Africa. BMC Public Health 2008;8(6):225.
of familial Hermansky-Pudlak syndrome. MedGenMed 25. Seo JH, Yu YS, Kim JH, et al. Correlation of visual
lems.5 The treatment for Hermansky
2003;5(1):3. acuity with foveal hypoplasia grading by optical coher-
Pudlak syndrome ranges from transfu- 5. Kaplan J, De Domenico I, Ward DM. Chediak- ence tomography in albinism. Ophthalmol 2007;114(8):
sion of platelets to medicating with Higashi syndrome. Curr Opin Hematol 2008;15(1):22-9. 1547-51.
6. Hutton SM, Spritz RA. A comprehensive genetic 26. Nurden P, Nurden AT. Congenital disorders associ-
antifibrinolytics to clotting factor
study of autosomal recessive ocular albinism in ated with platelet dysfunctions. Thromb Haemost
replacement therapy and stem-cell Caucasian patients. Invest Ophthalmol Vis Sci 2008;99(2):253-63.
transplantation.3,26 2008;49(3):868-72.