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Co nt act Le ns Pract ice
To Suzanne, Zoe and Bruce
 Co nt act Le ns
Pract ice

T h i r d Ed i t i o n

EDITED BY
Nat han Efro n
AC, DSc (Manche ste r), PhD, BScO p tom (Me lb ourne ),
FACO , FAAO , FIACLE, FCCLSA
Profe ssor Eme ritus, School of O p tome try,
Q ue e nsland Unive rsity of Te chnolog y,
Brisb ane , Australia

EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO

iii
© 2018 Elsevier Ltd. All rights reserved.

First published 2002

Reprinted 2005
Second edition 2010
Reprinted 2013
T ird edition 2018

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Notices

Knowledge and best practice in this f eld are constantly changing. As new research and experience broaden
our understanding, changes in research methods, pro essional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any in ormation, methods, compounds, or experiments described herein. In using such in ormation or
methods they should be mind ul o their own sa ety and the sa ety o others, including parties or whom they
have a pro essional responsibility.
With respect to any drug or pharmaceutical products identif ed, readers are advised to check the most
current in ormation provided (i) on procedures eatured or (ii) by the manu acturer o each product to be
administered, to veri y the recommended dose or ormula, the method and duration o administration, and
contraindications. It is the responsibility o practitioners, relying on their own experience and knowledge o
their patients, to make diagnoses, to determine dosages and the best treatment or each individual patient, and
to take all appropriate sa ety precautions.
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 CO NTENTS

Contrib uting Authors vii 13 Rig id Le ns O p tics 130

W NEIL CHARMAN
Pre ace to the Third Ed ition ix
14 Rig id Le ns Me asure me nt 136
Trib ute s x KLAUS EHRMANN

Acknowle d g e me nts xi 15 Rig id Le ns De sig n and Fitting 143

GRAEME YO UNG

PART 1 Int ro d uct io n 16 Rig id Toric Le ns De sig n and Fitting 156

RICHARD G LINDSAY

1 History 3 17 Rig id Le ns Care Syste ms 163

NATHAN EFRO N
PHILIP B MO RGAN

2 Ante rior Eye 10

JO HN G LAWRENSO N
PART 4 Le ns Re p lace me nt
3 Visual O p tics 28 Mo d alit ie s
W NEIL CHARMAN
18 Daily Disp osab le So t Le nse s 167
NATHAN EFRO N

PART 2 So ft Co nt act Le nse s

19 Re usab le So t Le nse s 175
4 So t Le ns Mate rials 45 JO E TANNER | NATHAN EFRO N

CARO LE MALDO NADO -CO DINA

20 Planne d Re p lace me nt Rig id Le nse s 187
5 So t Le ns Manu acture 61 CRAIG A WO O DS

NATHAN EFRO N

6 So t Le ns O p tics 68 PART 5 Sp e cial Le nse s and Fit t ing

W NEIL CHARMAN
Co nsid e rat io ns
7 So t Le ns Me asure me nt 73 21 Scle ral Le nse s 195
KLAUS EHRMANN
NATHAN EFRO N

8 So t Le ns De sig n and Fitting 86 22 Tinte d Le nse s 204

GRAEME YO UNG
NATHAN EFRO N | SUZANNE E EFRO N

9 So t Toric Le ns De sig n and Fitting 95 23 Pre sb yop ia 214

RICHARD G LINDSAY
JO HN MEYLER | DAVID RUSTO N

10 So t Le ns Care Syste ms 103 24 Exte nd e d We ar 231

PHILIP B MO RGAN
NO EL A BRENNAN | M-L CHANTAL CO LES

25 Sp ort 246
PART 3 Rig id Co nt act Le nse s NATHAN EFRO N

11 Rig id Le ns Mate rials 115 26 Ke ratoconus 251

NATHAN EFRO N LAURA E DO WNIE | RICHARD G LINDSAY

12 Rig id Le ns Manu acture 123 27 Hig h Ame trop ia 263

NATHAN EFRO N JO SEPH T BARR

v
vi CO NTENTS

28 Bab ie s and Child re n 268 41 Dig ital Imag ing 410

CINDY TRO MANS | HELEN WILSO N ADRIAN S BRUCE | MILTO N M HO M

29 The rap e utic Ap p lications 275 42 Comp liance 420

NATHAN EFRO N | SUZANNE E EFRO N NATHAN EFRO N

30 Post-re ractive Surg e ry 282 43 Practice Manag e me nt 427

SUZANNE E EFRO N NIZAR K HIRJI

31 Post-ke ratop lasty 287

BARRY A WEISSMAN
Ap p e nd ice s
32 O rthoke ratolog y 296 A Contact Le ns De sig n and Sp e cif cations 438
PAUL GIFFO RD

B Contact Le ns Tole rance s 440

33 Myop ia Control 306
PADMAJA SANKARIDURG | BRIEN A HO LDEN
C Ve rte x Distance Corre ction 441
34 Diab e te s 314
CLARE O ’DO NNELL
D Corne al Curvature – Corne al Powe r
Conve rsion 443

E Exte nd e d Ke ratome te r Rang e Conve rsion 445

PART 6 Pat ie nt Examinat io n and
Manag e me nt F So t Le ns Ave rag e Thickne ss 446
35 History Taking 323 G So t Le ns O xyg e n Pe r ormance 447
JAMES S W WO LFFSO HN

H Constant Ed g e Cle arance Rig id Le ns

36 Diag nostic Instrume nts 327 De sig ns 449
LYNDO N W JO NES | SRUTHI SRINIVASAN | ALISO N NG |
MARC SCHULZE
I So t Toric Le ns Misalig nme nt
37 Pre liminary Examination 346 De monstrator 450
ADRIAN S BRUCE
J Dry-e ye Q ue stionnaire 451
38 Patie nt Ed ucation 356
SARAH L MO RGAN K E ron Grad ing Scale s or Contact Le ns
Comp lications 453
39 A te rcare 364
LO RETTA B SZCZO TKA-FLYNN | NATHAN EFRO N L Scle ral Le ns Fit Scale s 456

40 Comp lications 385

NATHAN EFRO N Ind e x 459
 CO NTRIBUTING AUTHO RS

J o se p h T Barr, O D, MS, FAAO Suzanne E Efro n, BSc(Ho ns), MPhil,

Emeritus Pro essor, College o Optometry, T e Ohio State PGCe rt O cThe r
University, Columbus, Ohio, USA Locum Optometrist, Broadbeach, Queensland, Australia
27 High Ametropia 22 inted Lenses
29 T erapeutic Applications
No e l A Bre nnan, MScO p t o m, PhD, FAAO , 30 Post-re ractive Surgery
FCLSA
Clinical Research Fellow and Global Plat orm Lead, Myopia Klaus Ehrmann
Control, Johnson & Johnson Vision Care Inc., Jacksonville, Director – echnology, Brien Holden Vision Institute,
Florida, USA University o New South Wales, Sydney, Australia
24 Extended Wear 7 Sof Lens Measurement
14 Rigid Lens Measurement
Ad rian S Bruce , BScO p t o m, PhD, FAAO , FVCO
Lead Optometrist, Australian College o Optometry, Paul Giffo rd , PhD, MSc, BSc(Ho ns), MCO p t o m,
Melbourne, Victoria, Australia; Senior Fellow, Department FBCLA, FIACLE, FAAO
o Optometry and Vision Sciences, University o Melbourne, Private Practice, Brisbane, Queensland, and Adjunct Senior
Parkville, Victoria, Australia Lecturer, University o New South Wales, Sydney, Australia
37 Preliminary Examination 32 Orthokeratology
41 Digital Imaging
Nizar K Hirji, BSc, PhD, MBA, FCO p t o m,
M-L Chant al Co le s, BS, O D FAAO , FIMg t
Optometrist, Johnson & Johnson Vision Care Inc., Optometrist and Principal Consultant, Hirji Associates,
Jacksonville, Florida, USA Birmingham, UK; Visiting Pro essor o Optometry,
24 Extended Wear University o Manchester, Manchester, UK; Visiting
Pro essor o Optometry, City University, London, UK
W Ne il Charman, BSc, PhD, DSc, FO p t So cAm, 43 Practice Management
FCO p t o m(Ho n)
Emeritus Pro essor, T e University o Manchester, Manchester, UK Brie n A Ho ld e n, O AM, PhD, DSc(Ho n),
3 Visual Optics BAp p Sc, LO Sc (d e ce ase d )
6 Sof Lens Optics Founding Chie Executive O cer, Brien Holden Vision
13 Rigid Lens Optics Institute, University o New South Wales, Sydney, Australia
33 Myopia Control
Laura E Do w nie , PhD, BO p t o m, PGCe rt O cThe r,
FACO , FAAO , Dip Mus(Prac), AMusA Milt o n M Ho m, O D, FAAO FACAAI(Sc)
Lecturer and NHMRC ranslating Research Into Practice Private Practice, Azusa, Cali ornia, USA
( RIP) Fellow, Department o Optometry and Vision 41 Digital Imaging
Sciences, T e University o Melbourne, Parkville,
Victoria, Australia Lynd o n W J o ne s, PhD, FCO p t o m, Dip CLP,
26 Keratoconus Dip O rt h, FAAO , FIACLE, FBCLA
University Research Chair, Pro essor, School o Optometry
Nat han Efro n, AC, DSc, PhD, BScO p t o m, FACO , and Vision Science, and Director, Centre or Contact
FAAO , FIACLE, FCCLSA Lens Research, University o Waterloo, Waterloo, Ontario,
Pro essor Emeritus, School o Optometry, Queensland Canada
University o echnology, Brisbane, Queensland, Australia 36 Diagnostic Instruments
1 History
5 Sof Lens Manu acture J o hn G Law re nso n, BSc, PhD, MCO p t o m
11 Rigid Lens Materials Pro essor o Clinical Visual Science, City, University o
12 Rigid Lens Manu acture London, London, UK
18 Daily Disposable Sof Lenses 2 Anterior Eye
19 Reusable Sof Lenses
21 Scleral Lenses Richard G Lind say, BScO p t o m, MBA, FAAO ,
22 inted Lenses FCLSA, FVCO
25 Sport Private Practice, East Melbourne, Victoria, Australia
29 T erapeutic Applications 9 Sof oric Lens Design and Fitting
39 Af ercare 16 Rigid oric Lens Design and Fitting
40 Complications 26 Keratoconus
42 Compliance
vii
viii CO NTRIBUTING AUTHO RS
Caro le Mald o nad o -Co d ina, BSc(Ho ns), MSc,
PhD, MCO p t o m, FAAO , FBCLA
Senior Lecturer in Optometry, T e University o Manchester,
Manchester, UK
4 Sof Lens Materials
J o hn Me yle r, BSc(Ho ns), FCO p t o m, Dip CLP
Senior Director, Global Pro essional Af airs, Johnson &
Johnson Vision Care Companies, Wokingham,
Berkshire, UK
23 Presbyopia
Philip B Mo rg an, BSc(Ho ns), PhD, MCO p t o m,
FAAO , FBCLA
Pro essor o Optometry and Director, Eurolens Research,
T e University o Manchester, Manchester, UK
10 Sof Lens Care Systems
17 Rigid Lens Care Systems
Sarah L Mo rg an, BSc(Ho ns), MPhil, MCO p t o m,
FAAO , FBCLA
Staf Development Consultant, Manchester, UK;
Vision Sciences Fellow in Optometry, T e University
o Manchester, Manchester, UK
38 Patient Education
Aliso n Ng , PhD, MCO p t o m
Post Doctoral Fellow, Centre or Contact Lens Research,
University o Waterloo, Waterloo, Ontario, Canada
36 Diagnostic Instruments
Clare O ’Do nne ll, BSc(Ho ns), MBA, PhD,
MCO p t o m, FAAO , FBCLA
Head o Eye Sciences, Optegra Manchester Eye Hospital,
Didsbury; Reader, Aston University, Birmingham, UK
34 Diabetes
David Rust o n, BSc, FCO p t o m, Dip CLP, FAAO ,
FIACLE
Director, Global Pro essional Af airs, Johnson & Johnson
Vision Care Companies, Wokingham, Berkshire, UK
23 Presbyopia
Pad maja Sankarid urg , BO p t o m, MIP, PhD
Associate Pro essor, Program Leader – Myopia, Manager,
Intellectual Property, Brien Holden Vision Institute,
University o New South Wales, Sydney, Australia
33 Myopia Control
Marc Schulze , PhD, Dip lIng (AO ), FAAO
Clinical Scientist, Centre or Contact Lens Research,
University o Waterloo, Waterloo, Ontario, Canada
36 Diagnostic Instruments
Srut hi Srinivasan, PhD, BS O p t o m, FAAO
Clinical Research Manager and Senior Clinical Scientist,
Centre or Contact Lens Research, University o Waterloo,
Waterloo, Ontario, Canada
36 Diagnostic Instruments
Lo re t t a B Szczo t ka-Flynn, O D, PhD, FAAO
Pro essor, Department o Ophthalmology and Visual Science,
Case Western Reserve University; Director, Contact Lens
Service, University Hospitals Case Medical Center,
Cleveland, Ohio, USA
39 Af ercare
J o e Tanne r, BO p t o m
Pro essional Services Manager, CooperVision Australia and
New Zealand
19 Reusable Sof Lenses
Cind y Tro mans, BSc(Ho ns), PhD, MCO p t o m,
Dip (Tp )IP, FEAO O
Consultant Optometrist, Manchester Royal Eye Hospital;
Honorary Clinical Lecturer, Department o Ophthalmology,
T e University o Manchester, Manchester, UK
28 Babies and Children
Barry A We issman, O D, PhD, FAAO
Pro essor o Optometry, Southern Cali ornia College o
Optometry at Marshall B Ketchum University, Fullerton,
Cali ornia, USA; Emeritus Pro essor o Ophthalmology,
Stein Eye Institute, David Gef en School o Medicine at
UCLA, Los Angeles Cali ornia, USA
31 Post-keratoplasty
He le n Wilso n, BSc(Ho ns), MCO p t o m, Dip Tp (IP),
Dip O C, Dip Glauc
Principal Optometrist, Manchester Royal Eye Hospital,
Manchester, UK.
28 Babies and Children
J ame s S W Wo lffso hn, BSc(Ho ns), PGCe rt HE,
PGDip Ad vClinO p t o m, MBA, PhD, FCO p t o m,
FHEA, FSB, FAAO , FIACLE, FBCLA
Pro essor and Deputy Executive Dean, School o Li e and
Health Sciences, Aston University, Birmingham, UK
35 History aking
Craig A Wo o d s, BSc(Ho ns), PhD, MCO p t o m,
Dip CLP, PGCe rt O cThe r, FAAO , FACO , FBCLA
Pro essor, Head o Clinical Partnerships, Deakin Optometry,
School o Medicine, Deakin University, Geelong, Australia
20 Planned Replacement Rigid Lenses
Grae me Yo ung , BSc, MPhil, PhD, FCO p t o m,
Dip CLP, FAAO
Director, Visioncare Research, Farnham, Surrey; Honorary
Pro essor, School o Li e and Health Sciences, Aston
University, Birmingham, UK
8 Sof Lens Design and Fitting
15 Rigid Lens Design and Fitting
 PREFACE TO THE THIRD EDITIO N
T is book strives to achieve the ‘middle ground’ among contact
lens textbooks. It is not intended to be a brie clinical manual o
contact lens tting; nor is it intended to be a weighty tome with
extensive research coverage. Like its predecessors, this third
edition o Contact Lens Practice seeks to be a comprehensive,
easily accessible book that provides in ormation o immediate
relevance to contact lens practitioners, underpinned by well-
ounded evidence and expert clinical insight by the authors
o the various chapters, each o whom is an expert in the area
covered.
T is new edition is not just a cosmetic make-over. T ere
have been extensive revisions to most chapters, many o which
have been written by authors who are new or this edition.
T ere is also a new chapter on myopia control – an area o
considerable interest at present in view o the current myo-
pia epidemic (especially in Asia), and the potential or tting
contact lenses that can arrest myopia progression to a cer-
tain degree. T e chapter on daily disposable lenses has been
updated and expanded, which is particularly important given
that this modality now represents nearly one-third o contact
lenses prescribed worldwide.
I hope that students using this book nd it to be a valuable
guide to their studies and acquisition o knowledge in the sci-
ence and art o contact lens tting, and I trust that this work
will be a valuable companion to practitioners in their ef orts to
satis y the needs o those patients tted with contact lenses.
Professor Nathan Efron AC
ix
TRIBUTES
Here we pay tribute to two contributors to Contact Lens Practice
who have passed away since the second edition o this book was
published.
Keith Edwards, who wrote the chapter on History Taking
in the rst two editions o this book, lost a long- ought battle
with cancer in 2014. Keith was an inspirational educator, cli-
nician and researcher who had an impact internationally in
the eld o contact lenses and intraocular lenses. Following
his Optometry degree at City University, he worked in private
practice and served as secretary o the London Re raction Hos-
pital and examinations advisor at the College o Optometrists.
He was an inaugural director o Optometric Educators Ltd and
later worked or Madden and Layman, which was acquired by
Bausch & Lomb in the late 1980s. He expanded his role rom
UK Pro essional Services to Director o Global Clinical Devel-
opment or Surgical at Bausch & Lomb, which took him to the
US, where his nal job was as Vice-President o Clinical and
Regulatory A airs at LENSAR.
x
Brien Holden, who co-authored the chapter in this book on
Myopia Control, passed away suddenly in 2015. He was Chie
Executive O cer o the Brien Holden Vision Institute and Pro-
essor at the School o Optometry and Vision Science at the
University o New South Wales, Australia. Pro essor Holden
was a global leader in eye care and vision research, and an inter-
nationally renowned and awarded scientist and humanitarian.
He was widely acknowledged as the most inf uential optome-
trist o our generation. His career was spent inspiring scientists
and health-care pro essionals around the world with his dream
o ‘vision or everyone, everywhere’. Pro essor Holden was the
recipient o seven honorary doctorates rom universities around
the world, and was awarded an Order o Australia Medal or his
work in eye health and vision science.

I am grate ul to the contributing authors o this third edition o
Contact Lens Practice. All have worked diligently to update their
chapters, or write new chapters, to bring the latest clinically rel-
evant in ormation to the ore.
I continue to enjoy the strong support o the long-standing
publisher o all o my books – Elsevier. In particular, I am grate-
ul to Russell Gabbedy (Commissioning Editor) and Alexan-
dra Mortimer (Development Editor) or their encouragement
and support during the planning and production o this book.
T anks also to Samuel Crowe, or assisting e ciently with vari-
ous aspects o production.
Editing a book o this size and scope is a substantial undertak-
ing, and in this regard I wish to o er special thanks to my lovely
wi e, Suzanne, who has served as a ‘virtual co-editor’ by way o
ACKNO WLEDGEMENTS
spending many long hours assisting me in assembling, editing,
organizing and proo reading the contributed material. She has
done a wonder ul job. I really could not have completed this task
without her assistance. I also thank Suzanne or co-authoring
Chapters 22 and 29 with me, and or revising and authoring
Chapter 30.
Let me also pay tribute to the photographers and illustra-
tors, many o whom were not contributing authors o this
book, or their extraordinary skills and insights in creating
such antastic imagery. I also thank them or giving me per-
mission to use this material in the book. I apologize i I have
made any errors in attribution; please let me know i I have
erred in this regard, and I shall correct this at the f rst reprint-
ing opportunity.
xi
This pa ge inte ntiona lly le ft bla nk
 PART

1
Int ro d uct io n

PART O UTLINE
1 History 3
Nathan E ron
2 Ante rior Eye 10
John G Lawre nson
3 Visual O p tics 28
W Ne il Charman
This pa ge inte ntiona lly le ft bla nk
 1
Hist o ry
NATHAN EFRO N

Int ro d uct io n snugly into the orbital rim (Young, 1801) (Figs. 1.3 and 1.4).
A microscope eyepiece was tted into the base o the eyecup,
thus orming a similar system to that used by Descartes. Young’s
We canno t co nt inue t he se b rilliant succe sse s in t he invention was somewhat more practical in that it could be held
fut ure , unle ss we co nt inue t o le arn fro m t he p ast . in place with a headband and blinking was possible; however,
Calvin Coolid g e , inaug ural US p re sid e ntial ad d re ss, 1923 he did not intend this device to be used or the correction o
re ractive errors.
Coolidge was re erring to the successes o a nation, but his In a ootnote in his treatise on light in the 1845 edition o
sentiment could apply to any eld o endeavour, including con- the Encyclopedia Metropolitana, Sir John Herschel suggested
tact lens practice. As we continue to ride on the crest o a huge two possible methods o correcting ‘very bad cases o irregular
wave o exciting developments in the 21st century, we would not cornea’: (1) ‘applying to the cornea a spherical capsule o glass
wish to lose sight o the past. Hence the inclusion in this book o
this brie historical overview.
Outlined below in chronological order (allowing or some
historical overlaps) is the development o contact lenses, rom
the earliest theories to present-day technology. Each heading,
which represents a major achievement, is annotated with a year
that is considered to be especially signi cant to that develop-
ment. T ese dates are based on various sources o in ormation,
such as dates o patents, published papers and anecdotal reports.
It is recognized, there ore, that some o the dates cited are open
to debate, but they are nevertheless presented to provide a rea-
sonable chronological perspective.

Early The o rie s (1508–1887)

Although contact lenses were not tted until the late 19th cen- Fig . 1.1 Id e a o Le onard o d a Vinci to alte r corne al p owe r.
tury, a number o scholars had earlier given thought to the
possibility o applying an optical device directly to the eye-
ball to correct vision. Virtually all o these suggestions were
impractical.
Many contact lens historians point to Leonardo da Vinci’s
Codex o the Eye, Manual D, written in 1508, as having intro-
duced the optical principle underlying the contact lens. Indeed,
da Vinci described a method o directly altering corneal power
– by immersing the eye in a bowl o water (Fig. 1.1). O course,
a contact lens corrects vision by altering corneal power. How-
ever, da Vinci was primarily interested in learning the mecha-
nisms o accommodation o the eye (Heitz and Enoch, 1987) Fig . 1.2 Fluid -f lle d tub e d e scrib e d b y Re né De scarte s.
and did not re er to a mechanism or device or correcting
vision.
In 1636, René Descartes described a glass uid- lled tube
that was to be placed in direct contact with the cornea (Fig. 1.2).
T e end o the tube was made o clear glass, the shape o which
would determine the optical correction. O course, such a device
is impractical as blinking is not possible; nevertheless, the prin-
ciple o directly neutralizing corneal power used by Descartes is
consistent with the principles underlying modern contact lens
design (Enoch, 1956).
As part o a series o experiments concerning the mecha-
nisms o accommodation, T omas Young, in 1801, constructed
a device that was essentially a uid- lled eyecup that tted Fig . 1.3 Eye cup d e sig n o Thomas Young .
3
4 PART 1 Int ro d uct io n

Fig . 1.4 Thomas Young .

Fig . 1.6 Ad ol Gaston Eug e ne Fick.

Fig . 1.5 ‘Animal je lly’ sand wiche d b e twe e n a ‘sp he rical cap sule o
g lass’ (contact le ns) and corne a, as p rop ose d b y Sir Jo hn He rsche l.

lled with animal jelly’ (Fig. 1.5), or (2) ‘taking a mould o the
cornea and impressing it on some transparent medium’ (Her-
schel, 1845). Although it seems that Herschel did not attempt to
conduct such trials, his latter suggestion was ultimately adopted
some 40 years later by a number o inventors, working indepen-
dently and unbeknown to each other, who were all apparently
unaware o the writings o Herschel.

Glass Scle ral Le nse s (1888)

T ere was a great deal o activity in contact lens research in the late
1880s, which has led to debate as to who should be given credit
or being the rst to t a contact lens. Adol Gaston Eugene Fick
(Fig. 1.6), a German ophthalmologist working in Zurich, appears
to have been the rst to describe the process o abricating and
tting contact lenses in 1888; speci cally, he described the tting
o a ocal scleral contact shells rst on rabbits, then on himsel and
nally on a small group o volunteer patients (E ron and Pearson,
1988). In their textbook dated 1910, Müller and Müller, who were
manu acturers o ocular prostheses, described the tting in 1887
o a partially transparent protective glass shell to a patient re erred
to them by Dr Edwin T eodor Sämisch (Müller and Müller,
1910). Pearson (2009) asserts that the tting was done by Albert
C Müller-Uri. Fick’s work was published in the journal Archiv ür
Augenheilkunde in March 1888, and must be accorded historical
precedence over later anecdotal textbook accounts.
French ophthalmologist Eugène Kalt (Fig. 1.7) tted two
keratoconic patients with a ocal glass scleral shells and obtained
Fig . 1.7 Eug è ne Kalt.
a signi cant improvement in vision. A report o this work, pre-
sented to the Paris Academy o Medicine on 20 March, 1888
by Kalt’s senior medical colleague, Pro essor Photinos Panas,
acknowledges and there ore e ectively con rms that the work
o Fick occurred earlier (Pearson, 1989).
Credit or tting the rst powered contact lens must be given
to August Müller (Fig. 1.8) (no relation to Müller and Müller,
mentioned above), who conducted his work while he was a med-
ical student at Kiel University in Germany (Pearson and E ron,
1989). In his inaugural dissertation presented to the Faculty o
Medicine in 1889, Müller described the correction o his own
high myopia with a powered scleral contact lens. Paradoxically,
Müller subsequently lost interest in ophthalmology and went on
to practise as an orthopaedic specialist.

Fig . 1.8 Aug ust Mülle r. (Courte sy of Richard Pe arson.)
T e lenses worn by Müller were made by an optical engineer,
Karl Otto Himmler (1841–1903), whose rm enjoyed, until the
outbreak o World War II, an international reputation or the
manu acture o microscopes and their accessories. Himmler
must there ore be acknowledged as the rst manu acturer o
optically ground contact lenses (Pearson, 2007).
Little development occurred in the 50 years subsequent to
these early clinical trials. Improvements in methods o scleral
lens tting were described by clinicians such as Dallos, who
emphasized the importance o designing the lens to acilitate
tear ow beneath the lens (Dallos, 1936). Dallos also went on
to develop techniques or taking impressions o the human eye
and grinding the lenses rom these impressions.
Plast ic Scle ral Le nse s (1936)
Carl Zeiss o Jena, Germany applied or a patent that proposed
the manu acture o contact lenses rom ‘cellon, celluloid or an
organic substance with similar mechanical and optical prop-
erties’, which was eventually issued in 1923 (Pearson, 2015).
Cellon is cellulose acetate and celluloid is cellulose nitrate plas-
ticized with camphor; there ore, this is a re erence to a lens
made o a plastic material. T is was also the rst mention o
the manu acture o contact lenses by moulding. T e Zeiss pat-
ents envisaged that contact lenses made rom plastic materi-
als would be less expensive, have some exibility that would
improve the t, be ‘unbreakable’ and o er ocular protection
(Pearson, 2015).
It appears that in Germany there may have been some largely
unsuccess ul attempts to t plastic lenses rom around 1930.
It was reported in that year that Zeiss contact lenses moulded
rom cellon and celluloid lacked the degree o polish achieved
with glass lenses and were unstable owing to the in uences o
humidity and temperature. More serious ndings were that they
put a ‘tourniquet’ on the conjunctiva in the region o the lim-
bus and caused extensive corneal erosion. T ese un avourable
results were possibly due to the act that they were made with a
single back scleral radius o 12 mm (Pearson, 2015).
1 Hist o ry 5
T e Rohm and Haas company introduced transparent plas-
tic (polymethyl methacrylate: PMMA) into the USA in 1936,
and in the same year Feinbloom (1936) described a scleral lens
consisting o an opaque plastic haptic portion and a clear glass
centre. Soon a er, scleral lenses were abricated entirely rom
PMMA using lathing techniques. T e earliest report o the t-
ting o PMMA lenses appears to have been made by T ier in
1939. T ese lenses were said to be ‘about hal the weight o ordi-
nary glass, unbreakable and quicker to manu acture’. T ey did
not provoke any irritation, but the optical zone needed to be
repolished every 6 months (Pearson, 2015).
A key rationale or using PMMA or the manu acture o
contact lenses was that this material was considered to be bio-
logically inert in the eye. T is view was ormed by military
medical o cers who examined the eyes o pilots who su ered
eye injuries during World War II as a result o ragments rom
shattered cockpit windscreens (as would occur during aerial
dog ghts) becoming permanently embedded in the eye. T ese
eyes remained unreactive or years a er such accidents. Other
advantages o PMMA included its light weight, break resistance
and being easy to lathe and polish.
Plast ic Co rne al Le nse s (1948)
T e development o corneal lenses – or rigid lenses, as they are
re erred to today – began as the result o an error in the labora-
tory o optical technician Kevin uohy. During the lathing o a
PMMA scleral lens, its haptic and corneal portions separated.
uohy became curious as to whether the corneal portion could
be worn, so he polished the edge, placed it in his own eye and
ound that the lens could be tolerated (Bra , 1983). Further tri-
als were conducted, leading to the development o the rigid con-
tact lens (rigid lenses were previously re erred to as ‘hard’ lenses
i they were manu actured rom PMMA). uohy led a patent
or his invention in February 1948.
So began an era o popularization o the contact lens. T e
spherical uohy lens design su ered rom two main drawbacks:
considerable apical bearing, which caused central corneal abra-
sion and oedema, and excessive edge li , which made the lens
easy to dislodge. It was soon realized that these problems could be
overcome by altering the peripheral curvature o the posterior lens
sur ace, heralding the development o multicurve and aspheric
designs, which remain in widespread use today, albeit with supe-
rior gas-permeable materials (PMMA is now virtually obsolete).
Silico ne Elast o me r Le nse s (1965)
Silicone rubber orms a unique category amongst contact lens
materials. It is a ‘so lens’ in terms o its physical behaviour and
lenses are abricated rom this material in the orm o a so lens.
Unlike all other so lens materials, silicone elastomer does not
contain water and in this respect is analogous to a hard lens
material. Silicone elastomer is highly permeable to oxygen and
carbon dioxide and there ore provides minimal inter erence to
corneal respiration; however, it is di cult to manu acture and
its sur ace is hydrophobic and must be treated to allow com ort-
able wear. T e considerable di culties involved in enhancing
sur ace wettability have limited the clinical application o this
lens, and ew advances have been made since it was originally
tted. T e precise date o silicone elastomer lenses becoming
commercially available is unclear. T ere was some patent activ-
ity in the mid 1960s to early 1970s, and Mandell (1988) claims
6 PART 1 Int ro d uct io n
to have personally observed ten patients who were wearing such
lenses in 1965, noting very poor clinical results.
So ft Le nse s (1972)
Possibly the greatest understatement that can be ound in the
literature pertaining to contact lens development is the nal
sentence o a paper entitled ‘Hydrophilic gels or biological use’,
published in Nature on 9 January, 1960, by Wichterle and Lim
(1960): ‘Promising results have also been obtained in experi-
ments in other cases, or example, in manu acturing contact
lenses, arteries, etc.’
Initial attempts by Otto Wichterle (Fig. 1.9) to produce so
lenses abricated rom hydroxyethyl methacrylate (HEMA), and
manu actured using cast moulding, met with limited success.
Unable to attract support rom the Institute o Macromolecular
Research in Czechoslovakia (now the Czech Republic) where
he worked, and indeed discouraged by his superiors, Wichterle
was orced to conduct urther secret experiments in his own
home. Working with a children’s mechanical construction kit,
Wichterle developed the spin-casting technique (Fig. 1.10) and
Fig . 1.9 O tto Wichte rle . (Courte sy of De b b ie Swe e ne y.)
Fig . 1.10 The p rototyp e sp in-casting machine b uilt at home b y Wich-
te rle using his son’s toy Me ccano construction se t.
eventually managed to persuade his peers to conduct urther
trials at the Institute. He claims to have produced ‘the rst suit-
able contact lenses’ in late 1961 (Wichterle, 1978), which pre-
sumably approximates to the rst occasion when a so lens was
actually worn on a human eye. T e patent to develop so con-
tact lenses commercially was subsequently acquired by Bausch
& Lomb in the USA, who introduced so lenses into the world
market in 1972.
Lenses manu actured rom HEMA were an immediate
market success, primarily by virtue o their superior com ort
and enhanced biocompatibility. However, clinical experi-
ence and laboratory studies indicated that the poor physi-
ological response o the anterior eye during wear o the early
thick HEMA lenses could be enhanced by making so lenses
more permeable to oxygen – speci cally by making them
thinner and o a higher water content. Much o the research
and development in contact lenses up to the present time
has been concerned with the development o materials and
lens designs that optimize biocompatibility, primarily by
enhancing corneal oxygenation and minimizing absorption
o proteins, lipids and other tear constituents (McMahon and
Zadnik, 2000).
Rig id Gas-p e rme ab le Le nse s (1974)
In most respects, PMMA is considered to be an ideal contact
lens material; however, its single drawback is its impermeability
to gases that are exchanged at the corneal sur ace as part o aer-
obic metabolism. Speci cally, oxygen is prevented rom moving
rom the atmosphere into the cornea, and carbon dioxide ef ux
into the atmosphere is impeded. T is drawback has been the
major driving orce in the development o rigid lens materials
that are permeable to gases.
One o the rst rigid gas-permeable materials to be tried was
cellulose acetate butyrate, which a orded some oxygen perme-
ability but was subject to warpage. In 1974, Norman Gaylord
managed to incorporate silicone into the basic PMMA struc-
ture, heralding the introduction o a new amily o contact lens
polymers known as silicone acrylates (Gaylord, 1974). Subse-
quently, other ingredients such as styrene and uorine have
been incorporated into rigid materials in attempts to enhance
material biocompatibility urther.
Disp o sab le Le nse s (1988)
In the early days o so lens development, patients would typi-
cally use the same pair o lenses until the lenses became too
uncom ortable to wear, caused severe eye reactions, or were
damaged or lost. It became apparent that lens deposition and
spoilation over time were major impediments to success ul
long-term lens wear. Although regular lens replacement was
an obvious solution to some o these problems, the high unit
cost o lenses proved to be a signi cant disincentive. In the early
1980s, orward-thinking practitioners – notably Klas Nilsson
o Gothenburg, Sweden – convinced patients o the bene ts o
replacing lenses on a regular basis (6-monthly in Nilsson’s case)
and began prescribing lenses in this way. A subsequent land-
mark scienti c publication co-authored by Nilsson – known as
the ‘Gothenburg study’ (Holden et al., 1985) – unequivocally
proved the bene ts o regular lens replacement. So was born the
concept o regular lens replacement, albeit relatively expensive
or the patient at the time.

I regular lens replacement were to become the norm, some-
thing had to be done about lens cost. A group o Danish cli-
nicians and engineers, led by ophthalmologist Michael Bay,
developed a moulding process so that low-cost, multiple indi-
vidual lens packs could be produced (Mertz, 1997). T is prod-
uct – known as ‘Danalens’ – was released into the Scandinavian
market in 1984 and must be recognized as the rst truly dispos-
able lens. However, the initial manu acturing process was crude
and numerous problems with the lenses and packaging were
reported (Benjamin et al., 1985; Bergmanson et al., 1987).
T e pharmaceutical giant Johnson & Johnson, which had
not previously been involved in the contact lens business,
purchased the Danalens technology in 1984 and completely
overhauled the lens polymer ormulation, packaging system
and moulding technology (Mertz, 1997). T e result was the
Acuvue lens, an inexpensive weekly-replacement extended-
wear lens, which was released in the USA in June 1988, and
worldwide shortly therea er. T e success o this lens elevated
Johnson & Johnson to a leadership position in the contact lens
market. All other major contact lens companies ollowed suit,
and today the majority o so lenses prescribed worldwide
(85%) are designed to be replaced monthly or more requently
(Morgan et al., 2015).
Daily Disp o sab le Le nse s (1994)
T e ultimate requency with which lenses can be replaced
is daily. A Scottish company, Award (which was acquired by
Bausch & Lomb in 1996), developed a manu acturing technique
whereby the male hal o the mould that ormed the lens became
the lens packaging. T is technique urther reduced the unit cost
o a lens, making daily disposability a viable proposition. T e
‘Premier’ daily disposable lens was launched in the UK in 1994.
Johnson & Johnson released the ‘1-Day Acuvue’ daily dispos-
able lens into western regions o the USA around the same time,
leading to an ongoing dispute as to which company (Award or
Johnson & Johnson) was the rst to release a daily disposable
contact lens into the market (Meyler and Ruston, 2006). CIBA
Vision entered the daily disposable lens market in 1997 with a
product called ‘Dailies’.
Silico ne Hyd ro g e l Le nse s (1998)
T e allure o a so contact lens made rom a material with a
phenomenally high oxygen per ormance never escaped the
contact lens industry. T e development o such a lens would be
critical to solving hypoxic lens-related problems, which severely
limit the clinical utility o contact lenses, especially or extended
wear. Silicone elastomers were the obvious answer, but, or rea-
sons outlined above, success ul lenses could never be produced
rom this material. Polymer scientists in the contact lens indus-
try had long recognized that many o the problems associated
with silicone elastomers or contact lens abrication could theo-
retically be overcome by creating a silicone–hydrogel hybrid.
A er more than a decade o intensive research and devel-
opment, two spherical-design silicone hydrogel lenses were
introduced into the market in 1998: Focus Night & Day (CIBA
Vision) and Purevision (Bausch & Lomb). T e introduction o
these lenses is considered by many to be the most signi cant
advance in contact lens material technology since the devel-
opment o HEMA by Wichterle in the 1960s. Within a decade
o these products entering the market, all major contact lens
1 Hist o ry 7
manu acturers had introduced silicone hydrogel lenses; this
lens type is now available in toric and multi ocal designs and
a range o replacement modalities, including daily disposable
lenses.
Myo p ia Co nt ro l Le nse s (2010)
In 2010, CooperVision released into some Asian markets a daily
disposable so lens that is designed to arrest the rate o progres-
sion o myopia. A variety o optical designs can be employed
to achieve this so-called ‘anti-myopia’ e ect. T e CooperVision
MiSight lens has a ‘dual- ocus’ design that contains a large cen-
tral correction area surrounded by concentric zones o alternat-
ing distant and near powers. T e near power is intended as a
‘treatment’ zone to prevent myopic progression (see Chapter 33
or a detailed account o myopia control lenses).
Co nt act Le ns ‘Flat Pack’ (2011)
Japanese manu acturer Menicon introduced an ultra-thin orm
o packaging – known as the ‘ at pack’ – or their ‘Magic’ brand
o daily disposable contact lenses. As well as being highly e -
cient or storage and convenient or the user, this orm o pack-
aging reduces lens contamination because the lens back sur ace
is always presented to the patient upon opening the pack, which
means that the person can pick up and insert the lens into the
eye without touching and contaminating the posterior lens sur-
ace, which comes into contact with the eye (Nomachi et al.,
2013). T e contact lens is essentially sandwiched within a 1 mm
thick aluminium oil sleeve that is resistant to evaporation, thus
preserving the small amount o uid trapped within the pack
that moisturizes the lens.
Fig. 1.11 presents a historical timeline o key developments
in the contact lens eld rom the time contact (scleral) lenses
were rst tted to human eyes in the late 1880s up to the
present.
The Fut ure
So lenses are likely to dominate the uture contact lens mar-
ket. Although rigid lenses are seldom tted today or purely
cosmetic reasons, there are many clinical indications or rigid
lenses, such as keratoconus, distorted corneas, irregular and / or
high astigmatism, certain anterior eye pathologies and par-
ticipation in extreme sports. Accordingly, specialized rigid
lens ttings will continue to be an important aspect o contact
lens practice, albeit at relatively low levels. T e recent renewed
interest in scleral or mini-scleral lenses is unlikely to have a sig-
ni cant impact on the overall proportion o lenses prescribed
owing to the specialist nature o tting such lenses.
T e convenience and ocular health bene ts o daily dispos-
able lenses are likely to see this modality o lens wear continue
to increase in popularity. T is trend will be accelerated with
improvements in methods and e ciency o lens mass produc-
tion, which in turn will drive prices down and make these lenses
more a ordable. O course, any increase in daily disposable
lens usage will be matched by a commensurate decrease in the
demand or, and use o , contact lens care solutions.
Silicone hydrogels are set to continue as the main material
type rom which lenses are abricated in view o their abil-
ity to obviate hypoxic complications o lens wear; however,
the possibility o the arrival in the uture o an entirely new
8 PART 1 Int ro d uct io n

Fig . 1.11 Historical time line o contact le ns d e ve lop me nt. PMMA = p o lyme thyl me thacrylate ; HEMA = hyd roxye thyl me thacrylate .

category o lens material with even greater bene ts should not
be discounted.
Contact lenses are likely to be used increasingly or the cor-
rection o presbyopia; this trend may be uelled by the devel-
opment o superior multi ocal lens designs and the increasing
availability o such products as daily disposable lenses. Look-
ing urther into the uture, contact lenses that switch power
electronically or through some other means may acilitate
enhanced presbyopic correction.
Extended wear is the ultimate modality in terms o patient
convenience, but it is unlikely that this modality o lens wear
will break through the ‘glass ceiling’ o a prescribing rate o
around 10% o lenses tted in the oreseeable uture, in view o
the ve times greater risk o microbial keratitis when sleeping in

all orms o contact lenses (Schein et al., 1989). Again, develop-
ment or invention o an entirely new category o lens material
with superior ocular biocompatibility or an ability to minimize
microbial colonization would need to be developed be ore
extended wear can capture an appreciably greater slice o the
contact lens market.
As better toric lens designs become available, especially in
daily disposable modality, toric lenses tting is likely to increase
steadily to represent approximately 45% o all so lenses pre-
scribed, which is the level at which all astigmatism ≥ 0.75 D is
being corrected. We may see a resurgence in tinted lens tting
as the newly developed coloured silicone hydrogel lenses gain in
popularity and similar products enter the market.
Finally, current developments in innovative contact lens appli-
cations – such as lens sur ace modi cations to include channels
and patterns or improving post-lens tear exchange (Weidemann
1 Hist o ry 9
and Lakkis, 2005; Lin et al., 2006), alternative anti-myopia designs
(Sankaridurg et al., 2011), anti-in ective and anti-in ammatory
lenses (Weisbarth et al., 2007; Zhu et al., 2008), drug delivery
(Mohammadi et al., 2014), glucose monitoring and other orms
o metabolic sensing (Farandos et al., 2015), intraocular pressure
measurement (Chen et al., 2014), digital in ormation acquisition
and display (e.g. a contact lens version o Google Glass [Google
Inc., Mountain View, CA]) and liquid crystal diode optical
switching (Milton et al., 2014) – may open up whole new markets
or contact lenses and move at least part o the industry in new
and interesting directions. Contact lens practitioners may need to
acquire new knowledge and tting skills so that they can embrace
any such innovative developments.
Acce ss t he co mp le t e re fe re nce s list o nline at
ht t p :/ / www.e xp e rt co nsult .co m.
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9.e 1
 2
Ant e rio r Eye
JO HN G LAWRENSO N

Int ro d uct io n
A critical aspect o contact lens practice is monitoring the
ocular response to lens wear, which ranges rom acceptable
physiological changes to adverse pathology. In order to do this,
practitioners must possess a thorough understanding o the
normal structure and unction o the anterior eye, which is the
subject o this chapter. In the course o reading other chapters
in this book, the reader may need to re er back to this chapter
on the unctional anatomy and physiology o the anterior eye
in order to develop a uller understanding o the phenomena
being described.
The Co rne a
cornea is conventionally divided into our zones (central, para-
central, peripheral and limbal). T e central zone, which covers
the entrance pupil o the eye, is spherical, approximately 4 mm
wide, and principally determines high-resolution image or-
mation on the ovea. T e paracentral zone, which lies outside
the central zone, is atter and becomes optically important in
dim illumination when the pupil dilates. T e peripheral zone
is where the cornea is attest and most aspheric (Klyce et al.,
1998). Due to a di erence in curvature between its posterior
and anterior sur aces, the cornea shows a regional variation
in thickness. Centrally the thickness is approximately 0.54
mm (Doughty and Zaman, 2000), with a peripheral thickness
between 11% and 19% higher than in the centre (Khoramnia
et al., 2007).

T e cornea ul ls two important unctions: together with the Microscop ic Anatomy

sclera it orms a tough brous outer coat that encloses the When the cornea is viewed in transverse section, ve distinct
ocular tissues and protects the internal components o the layers can be resolved: epithelium, Bowman’s layer, stroma, Des-
eye rom injury. Signi cantly, the cornea also provides two- cemet’s membrane and endothelium (Fig. 2.1).
thirds o the re ractive power o the eye. It is particularly well
suited to its role: the cornea is curved and transparent, and the Epithelium. T e epithelium represents approximately 10% o the
air–tear inter ace provides a re ractive sur ace o good optical thickness o the cornea (55 µm) (Feng and Simpson, 2008). It is a
quality. strati ed squamous non-keratinized epithelium, consisting o 5–6
layers o cells (Fig. 2.2), which undergo a constant process o cyclic
CO RNEAL ANATO MY
Gross Anatomy
T e cornea is elliptical when viewed rom in ront, with its long
axis in the horizontal meridian ( able 2.1). T is asymmetry is
produced by a greater degree o overlap o the peripheral cornea
by opaque limbal tissue in the vertical meridian. T e sur ace
area o the cornea is 1.1 cm 2, which represents about 7% o the
sur ace area o the globe (Maurice, 1984). opographically, the

TABLE Co rne al Dime nsio ns and Re lat e d

2.1 Me asure me nt s
Parame t e r Value
Are a 1.1 cm 2
Diame te r
Horizontal 11.8 mm
Ve rtical 10.6 mm
Rad ius of curvature
Ante rior ce ntral 7.8 mm
Poste rior ce ntral 6.5 mm
Thickne ss
Ce ntral 0.54 mm
Pe rip he ral 0.67 mm
Re fractive ind e x 1.376
Powe r 42 D Fig . 2.1 Transve rse se ction throug h the corne a. The stroma, which
re p re se nts 90% o the thickne ss o the corne a, is b ound e d b y the e p i-
(Data ad ap te d rom Bron e t al., 1997.) the lium (aste risk) and e nd othe lium (arrow).
10

shedding and replacement to maintain corneal integrity. T ree
distinct epithelial cell types are recognized: a single row o basal
cells, 2–3 rows o wing cells and 2–3 layers o super cial (squamous)
cells. In addition, several non-epithelial cells are present (e.g.
lymphocytes, macrophages and Langerhans cells). T e epithelium
orms a permeability barrier to water, ions and hydrophilic
molecules above a certain size, as well as orming an e ective
barrier to the entry o pathogens. Further epithelial specialization
enhances adhesion between cells, to withstand shearing and
abrasive orces. Furthermore, throughout the thickness o the
epithelium, adjacent cells are connected to one another by water
channels (aquaporins) that are engaged in transcellular water
transport and gap junctions to allow the trans er o ions and small
molecules between cells (Bron et al., 2015).
Super cial cells are structurally modi ed or their barrier
unction and interaction with the tear lm. Scanning elec-
tron microscopy o sur ace cells shows extensive nger-like
and ridge-like projections (microvilli and microplicae), which
increase the epithelial sur ace area. Light, medium and dark
cells can be distinguished depending on the number and pat-
tern o sur ace projections (P ster, 1973). It has been sug-
gested that dark cells, which are relatively ree o these sur ace
eatures, are close to being desquamated into the tear lm. By
contrast, the newly arrived light cells possess a more extensive
array o sur ace projections. In high-power transmission elec-
tron micrographs, microvilli and microplicae show an extensive
lamentous covering known as the glycocalyx. T e glycocalyx
is ormed rom membrane-bound mucin glycoproteins and is
important or spreading and attachment o the precorneal tear
lm. In accordance with their barrier unction, a complex net-
work o tight junctions links super cial cells that exclude water-
soluble dyes such as uorescein (Bron et al., 2015).
Wing cells are so named because o their characteristic
shape, with lateral extensions and a concave in erior sur ace to
accommodate the apices o the basal cells. T eir nuclei tend to
be spherical or elongated in the plane o the cornea. T e cell
borders o the polygonal wing cells show prominent in oldings
that interdigitate with adjacent cells, and numerous desmo-
somes. T is arrangement results in a strong intercellular adhe-
sion. T e cytoplasm contains prominent cytoskeletal elements
(predominantly actin and cytokeratin intermediate laments),
and although the usual complement o organelles is present they
are ew in number.
Fig . 2.2 Corne al e p ithe lium (d e tail). Thre e ce ll typ e s are p re se nt:
b asal ce lls (aste risk), wing ce lls (arrowhe ad ) and sq uamous ce lls (arrow).
BL= Bowman’s laye r.
2 Ant e rio r Eye 11
Basal cells consist o single-layer columnar cells with a verti-
cally oriented oval nucleus. Ultrastructurally, they are similar in
appearance to wing cells. T e plasma membrane similarly shows
pronounced in olding and the cytoplasm contains prominent
intermediate laments. A variety o cell junctions are present
including: desmosomes, which mediate adhesion between cells;
hemidesmosomes, which are involved in the attachment o basal
cells to the underlying stroma; and gap junctions, which allow or
intercellular metabolic coupling. Basal cells orm the germative
layer o the cornea, and mitotic cells are o en seen at this level.
Basal Lamina and Bowman’s Layer. T e basal lamina
(basement membrane) is synthesized by basal cells. It varies
in thickness between 0.5 and 1 µm, and under the electron
microscope can be di erentiated into an anterior clear zone
(lamina lucida) and a posterior darker zone (lamina densa).
T e basal lamina is part o a complex adhesion system, which
mediates the attachment o the epithelium to the underlying
stroma (Fig. 2.3). Hemidesmosomes link the cytoskeleton via a
series o anchoring brils to anchoring plaques in the anterior
stroma. T e molecular components o this adhesion complex
have been identi ed and include type VII collagen, integrins,
laminin and bullous pemphigoid antigen (Gipson et al., 1987).
Bowman’s layer (anterior limiting membrane) varies in thick-
ness between 8 and 14 µm. With the light microscope it appears as
an acellular homogeneous zone. Ultrastructurally, it is composed
o a randomly oriented array o ne collagen brils, which merge
with the brils o the anterior stroma (Hogan et al., 1971). Fibrils
are composed primarily o collagen types I, III and V. Collagen VII,
associated with anchoring brils, is also present. T ere is evidence
that Bowman’s layer is ormed and maintained primarily by the epi-
thelium, although its unction is unclear. T e absence o Bowman’s
layer rom the cornea o most mammals, and the act that corneas
devoid o this layer over the central cornea ollowing photore rac-
tive keratectomy (PRK) apparently unction normally, suggest that
it is not critical to corneal integrity (Wilson and Hong, 2000).
Stroma. T e stroma is approximately 500 µm thick, and
accounts or 90% o the thickness o the cornea. It is composed
predominantly o collagen brils (70% dry weight) embedded in
a highly hydrated matrix o proteoglycans. A variety o collagen
Fig . 2.3 Sche matic re p re se ntation o the ad he sion syste m o the cor-
ne al e p ithe lium. Inte rme d iate lame nts in the cytoske le ton (CS) are
linke d throug h he mid e smosome s (HD) via anchoring b rils (AF) to an-
choring p laq ue s (AP) in the ante rior stroma. BL= b asal lamina; D = d e s-
mosome .
12 PART 1 Int ro d uct io n
Fig . 2.4 Se ction throug h the stroma. Ke ratocyte s (arrowe d ) are locat-
e d b e twe e n lame llae .
Fig . 2.5 Ele ctron microg rap h o stromal lame llae that cross e ach othe r
ap p roximate ly at rig ht ang le s. Note the re g ular arrang e me nt o colla-
g e n b rils within lame llae .
types have been identi ed. ype I is the major bril- orming
collagen, with lesser amounts o types III and V. Non- bril-
orming collagens, including types VI and XII, are ound in the
inter brillar matrix (Meek and Boote, 2009). A section taken
perpendicular to the corneal sur ace reveals that the collagen
brils are arranged in 200–250 layers (lamellae) running parallel
to the sur ace (Fig. 2.4). Lamellae are approximately 2 µm thick
and 9–260 µm wide, and extend rom limbus to limbus. Fibrils
o adjacent lamellae make large angles with each other. In the
super cial stroma the angles are less than 90°, but brils become
orthogonal in the deeper stroma (Hogan et al., 1971; Meek and
Boote, 2009). T is pre erred orthogonal orientation gradually
changes in avour o circum erentially aligned collagen at the
limbus. T is particular arrangement o collagen imparts a high
tensile strength or corneal protection, which is important given
its exposed position. Within lamellae, all collagen brils are
parallel with uni orm size and separation (Fig. 2.5). Accurate
Fig . 2.6 Flat se ction throug h the stroma staine d with g old chlorid e .
Ke ratocyte s (arrowe d ) d isp lay a ste llate ap p e arance .
physiological measurements o collagen bre diameter and
spacing can be obtained or the hydrated cornea with the aid o
X-ray di raction. Using this technique, the mean bril diameter
in the human cornea is 31 nm, with an inter brillar spacing o
55 nm (Meek and Leonard, 1993). T is narrow bril diameter
and constant separation, which is a characteristic o corneal
collagen, are necessary prerequisites or transparency.
T e inter brillar space contains a matrix o proteoglycans
(approximately 10% o dry weight). T ese molecules are highly
sulphated, and along with bound chloride ions create a polyan-
ionic stromal inter brillar matrix that induces osmotic swelling.
As well as playing a major role in corneal hydration, collagen–
proteoglycan interactions are also thought to be important in
determining the size and spatial arrangement o stromal colla-
gen brils (Scott, 1991; Quantock and Young, 2008).
Collagen and proteoglycans are maintained by keratocytes.
T ese cells occupy 3–5% o stromal volume and lie between col-
lagen lamellae, attened in the plane o the cornea (Fig. 2.6).
Keratocyte density examined by con ocal microscopy and bio-
chemical methods (Møller-Pederson and Ehlers, 1995; Prydal
et al., 1998) is non-uni orm. Density decreases rom super cial
to deep stroma (Hollingsworth et al., 2001) and increases rom
centre to periphery. Keratocytes display a large central nucleus
and long slender processes extend rom the cell body. Processes
rom adjacent cells sometimes make tight junctions with each
other. Cell organelles are not numerous but the usual comple-
ment o organelles, including endoplasmic reticulum, Golgi
apparatus and mitochondria, can be observed (Hogan et al.,
1971).
Newer lamellar corneal transplantation techniques have
been developed that allow selective replacement o the diseased
corneal layers. Deep anterior lamellar keratoplasty (DALK),
which is increasingly being used to treat keratoconus and cor-
neal scarring, involves replacement o the a ected stroma while
retaining the host’s healthy Descemet’s membrane and endo-
thelium. Separation between the posterior stroma and Des-
cemet’s / endothelium can be achieved by intrastromal injection
o air, viscoelastic or saline. Dua and co-workers per ormed a
histological examination o donor corneas using air bubble sep-
aration and claimed to have identi ed a novel ‘pre-Descemet’s
posterior stromal layer’, which was widely publicized (Dua et al.,

Fig . 2.7 Hig h-p owe re d microg rap h o the p oste rior stroma. De s-
ce me t’s me mb rane (DM) is locate d b e twe e n the stroma (S) and the e n-
d othe lium (arro w).
Fig . 2.8 Thre e -d ime nsional re p re se ntation o the p oste rior corne a
showing the e nd othe lium (e ), De sce me t’s me mb rane (d ) and stroma (s).
A stromal lame lla has b e e n re f e cte d to re ve al an intralame llar ke rato-
cyte (k).
2013). However, the current consensus amongst corneal experts
is that this layer is not suf ciently unique to constitute a new
corneal layer (Jester et al., 2013).
Descemet’s Membrane. Descemet’s membrane is the basement
membrane o the corneal endothelium. It lies between the
endothelium and the overlying stroma (Fig. 2.7). At birth it is
3–4 µm thick, and increases to a thickness o 10–12 µm in the
adult. In the periphery o aged corneas, Descemet’s membrane
displays periodic sections o thickening, which are known as
Hassall–Henle warts. T e anterior one-third o Descemet’s
membrane represents that part produced in etal li e and, under
the electron microscope, is characterized by a periodic banded
pattern (Fig. 2.8). T e posterior two-thirds, which is ormed
postnatally, has a more homogeneous granular appearance.
Descemet’s membrane has a unique biochemical composition
in contrast with other basement membranes (Lawrenson
et al., 1998). T e major basement membrane collagen type is
type IV, whereas in Descemet’s membrane type VIII collagen
predominates.
Endothelium. T e endothelium is a monolayer o squamous
cells that lines the posterior sur ace o the cornea (Fig. 2.9)
and plays a critical role in maintaining corneal transparency
(Bonanno, 2012). As it has a limited capacity or mitosis to
2 Ant e rio r Eye 13
Fig . 2.9 Tang e ntial (f at) se ction throug h the corne al e nd othe lium: a
sing le laye r o p olyg onal ce lls with irre g ular b ord e rs can b e ob se rve d .
replace damaged or e ete cells, there is a progressive reduction
in endothelial cell number with age. At birth the cornea
contains a total o approximately 500 000 cells, which represents
a mean density o 4500 cells / mm 2. During in ancy, cell loss
is particularly marked and a 26% reduction occurs in the rst
year o li e (Sherrard et al., 1987). T erea er the rate o loss
progressively declines into old age. Since gra ed corneas appear
to maintain transparency and unctional normality with an
endothelial cell density o less than 1000 cells / mm 2, it seems
that normal cell density represents a considerable ‘physiological
reserve’ (Klyce and Beuerman, 1998). When viewed en ace, or
example using a specular microscope, the endothelium appears
as a mosaic o polygonal (typically hexagonal) cells (E ron et al.,
2001). In response to pathology, trauma, age and prolonged
contact lens wear, the endothelial mosaic becomes less regular,
and shows a greater variation in cell size (polymegethism) and
shape (pleomorphism) as cells spread to ll gaps caused by
cell loss. Under the electron microscope, the lateral borders o
the cells are markedly convoluted and adjacent cells are linked
by tight junctions (with less- requent gap junctions) (Hogan
et al., 1971). T e complement o organelles seen in endothelial
cells re ects their high metabolic activity, with numerous
mitochondria and a prominent rough endoplasmic reticulum.
CO RNEAL INNERVATIO N
Source and Distrib ution of Corne al Ne rve s
T e cornea is the most richly innervated sur ace tissue in
the body. Corneal nerves are responsible or the detection o
somatosensory stimuli and play an important role in initiating
the blink re ex, wound healing and tear secretion (see Sha-
heen et al., 2014, or a recent review). T e majority o corneal
nerves are sensory and derive rom the nasociliary branch o
the trigeminal nerve (Ruskell and Lawrenson, 1994). T ere is
also evidence or the existence o a modest sympathetic inner-
vation rom the superior cervical ganglion (Mar urt and Ellis,
1993). Branches rom the nasociliary nerve either pass directly
to the eye as long ciliary nerves or traverse the ciliary ganglion,
leaving it as short ciliary nerves that enter the eye close to the
14 PART 1 Int ro d uct io n
Fig . 2.10 Whole -mount g old chlorid e -staine d p re p aration o corne al
ne rve s (arrows) locate d at b asal le ve l.
optic nerve. Nerves destined or the cornea travel initially in
the suprachoroidal space, be ore crossing the sclera to advance
radially towards the cornea.
Most o the 50–80 precorneal nerve trunks, which contain
a mixture o myelinated and unmyelinated bre bundles, enter
the cornea at mid-stromal level. Myelin is soon lost and the
unmyelinated nerve bre bundles divide repeatedly and move
anteriorly to orm a rich plexi orm network in the anterior one-
third o the stroma. Axons are particularly dense immediately
beneath Bowman’s layer, orming an extensive subepithelial
plexus (Oliveira-Soto and E ron, 2001). From this plexus, axons
pass vertically through Bowman’s layer, losing their Schwann
cell sheath in the process. Upon entering the epithelium, axons
turn through 90° and divide into a series o ne branches that
course between basal cells (Fig. 2.10). Some branches pass into
the more super cial layers be ore terminating. T e density o
nerve terminals is greatest centrally, corresponding to approxi-
mately 600 terminals / mm 2, which results in large overlapping
receptive elds (Shaheen et al., 2014).
Corneal nerves display a complex neurochemistry. A variety
o neurotransmitters and neuromodulators have been identi-
ed, including acetylcholine, substance P, and calcitonin gene-
related peptide. However, it is unclear how these particular
neurochemicals correlate with unction (Belmonte et al., 1997).
Functional Consid e rations
Corneal nerves serve important sensory, re ex and trophic
unctions. Interest in the sensitivity o the cornea dates back to
the 19th century (Lawrenson, 1997), when the pioneering Ger-
man physiologist von Frey concluded that pain was the only
sensation perceived by the cornea. T is was consistent with his
theory o the speci city o sensory receptors, which maintained
that each sensory modality was subserved by a separate anatom-
ically distinct nerve terminal. In his experiments on the cornea,
von Frey could elicit only a sensation o pain and, as the cornea
contained exclusively ree (unspecialized) nerve endings, he
concluded that ree nerve endings were the exclusive receptors
or pain. Although the speci city theory has subsequently been
challenged, particularly with respect to its exclusivity, the ques-
tion as to whether pain is the only sensory modality perceived
by the cornea remains.
Modern experiments using care ully controlled corneal
stimulation, with a variety o mechanical, chemical and ther-
mal stimuli, have evoked only sensations o irritation or pain.
By contrast, electrophysiological studies o corneal a erent
neurones have identi ed neurones that respond to mechanical,
thermal and chemical stimulation. However, since the conscious
perception o these sensations has not been demonstrated, it
is likely that such speci city o modality is lost during central
nervous system processing. Electrophysiological recording also
allows or the mapping o receptive elds. T ese are o en large
and overlapping, which explains the inability o the cornea to
localize a stimulus accurately (Belmonte et al., 1997). T e sen-
sitivity o the cornea to mechanical stimulation is particularly
acute, and acts as a trigger or the protective blink and lacrimal
re exes. Cold receptors may be important in signalling evapo-
rative cooling, which is a major determinant o spontaneous eye
blink requency ( subota, 1998).
Corneal a erent bres also exert important trophic in u-
ences. Damage to corneal sensory nerves by surgery, trauma or
in ection produces neuroparalytic keratitis – a condition that is
characterized by progressive epithelial cell loss and oedema. T e
mechanism o this trophic role is not ully understood, although
the release o neuropeptides (e.g. substance P and calcitonin
gene-related peptide) may be a actor. Sympathetic nerves also
play a role in epithelial maintenance by regulating ion transport
processes, and cell proli eration and migration during wound
healing.
CO RNEAL METABO LISM
Source of O xyg e n and Nutrie nts
In order to per orm its vital unctions, the cornea requires a
constant supply o oxygen and other essential metabolites (e.g.
glucose, vitamins and amino acids). However, its avascularity
dictates that alternative routes must exist or the provision o its
metabolic needs. T ere are three possibilities: rom the perilim-
bal vasculature, rom the tear lm or rom the aqueous humour.
In open-eye conditions the bulk o the oxygen required or the
cornea is obtained rom the atmosphere via di usion across
the precorneal tear lm. Under steady-state conditions it can
be assumed that the tears are saturated with oxygen, and there-
ore at an oxygen tension corresponding to the atmosphere (155
mmHg at sea level). It has been estimated that the oxygen ten-
sion o the aqueous humour in the human eye lies between 30
and 40 mmHg (Klyce and Beuerman, 1998).
Experiments using nitrogen- lled goggles or sealed scleral
lenses have shown the corneal dependence on tear-side oxygen
to avoid oedema and maintain normal unction. T e reason
why the cornea swells during contact lens wear is explained in
Fig. 2.11. During eye closure the oxygen level in the tears is in
equilibrium with the palpebral vasculature (55 mmHg) (E ron
and Carney, 1979).
Signi cantly, corneal thickness increases by approximately
5% during sleep, and returns to baseline levels within 1 hour
o eye opening. It has been suggested that overnight swell-
ing is related to tear lm tonicity rather than reduced oxygen

Fig . 2.11 (A) Cross-se ction o an e ye we aring a contact le ns, which
imp e d e s ing re ss o oxyg e n into, and the e g re ss o carb on d ioxid e rom,
the corne a. (B) The contact le ns b locks oxyg e n sup p ly to the corne a (1),
causing lactic acid to accumulate in the stroma (2). This d raws in wate r
(3), le ad ing to stromal oe d e ma (4). (Ad ap te d rom E ron, N. (1997). Con-
tact le nse s and corne al p hysiolog y. Biol. Sci. Re v., 9, 29–31.)
availability (Klyce and Beuerman, 1998). T e oxygen ux into
the cornea can be measured using polarographic oxygen sen-
sors. It is in the region o 6 µl / cm 2 / h or the cornea as a whole,
although the consumption rate or its composite layers is not
equal. Consumption rates have been estimated as 40 : 39 : 21 or
the epithelium, stroma and endothelium, respectively (Free-
man, 1972).
Several lines o evidence indicate that the aqueous humour is
the primary source o glucose and essential amino acids or the
cornea (Maurice, 1984). T e glucose concentration o tears is
low compared with that in the aqueous humour, and the inser-
tion o nutrient-impermeable implants into the stroma results
in degeneration o the tissue lying anterior to the implant.
Although exogenous glucose is primarily utilized, glycogen
stores are present in all corneal cells to provide glucose in con-
ditions o metabolic stress.
T e role o the perilimbal vasculature in the provision o
oxygen and nutrients appears limited and it is likely that it is
signi cant only or the corneal periphery (Maurice, 1984).
O xid ative Me tab olism
T e cornea derives its energy principally rom the oxidative
breakdown o carbohydrates (Riley, 1969). Glucose, which
is the primary substrate or the generation o adenosine tri-
phosphate (A P), is catabolized by three metabolic pathways:
glycolysis, the tricarboxylic acid (Krebs) cycle and the hex-
ose monophosphate shunt (Fig. 2.12). Anaerobic glycolysis
accounts or the majority (85%) o glucose metabolism. In
this pathway, glucose is rst oxidized to pyruvate and then
subsequently reduced to lactate, with a net yield o two mol-
ecules o A P per mole o glucose. T e CA cycle results in
a greater energy yield (36 A P). T is pathway is most active
in the corneal endothelium, which has the greatest energy
requirement.
Metabolic waste products can be potentially damaging i
allowed to accumulate. Although carbon dioxide can readily
di use out o the cornea across its limiting layers, lactate is less
easily eliminated. Under normoxic conditions, lactate is able to
2 Ant e rio r Eye 15
Fig . 2.12 Me tab olic p athways p re se nt in the co rne a. HMP = he xose
monop hosp hate shunt; TCA cycle = tricarb oxylic acid (Kre b s) cycle ;
ATP = ad e nosine trip hosp hate ; NADPH = nicotinamid e ad e nine d inucle -
otid e p hosp hate (re d uce d orm).
di use slowly across the endothelium into the anterior cham-
ber. However, during periods o hypoxia the proportion o glu-
cose that is metabolized anaerobically increases. T e resulting
accumulation o lactate causes stromal oedema via an increased
osmotic load (Klyce, 1981) and localized tissue acidosis (Klyce
and Beuerman, 1998).
T e hexose monophosphate shunt (also known as the pen-
tose phosphate shunt) plays an important role in the corneal
epithelium (Berman, 1981), where it ul ls several important
unctions, including the generation o intermediates or biosyn-
thetic reactions and the prevention o oxidative damage by ree
radicals.
CO RNEAL TRANSPARENCY
Under normal conditions the cornea is highly transparent,
transmitting more than 90% o incident light. Structurally, the
cornea is a typical connective tissue consisting principally o a
matrix o collagen and proteoglycans. Under normal circum-
stances such an arrangement would avour light scatter with
consequent loss o transparency. T is raises two undamental
questions: how is transparency achieved, and how is it main-
tained? o begin to answer these questions it is necessary to
understand the spatial organization o the stromal matrix and
the importance o corneal hydration control.
Stromal O rg anization
Maurice (1957) explained the transparency o the cornea on the
basis o the small diameter and regular separation o the stro-
mal collagen. He suggested that the collagen brils o the stroma
were disposed in a regular crystalline lattice, and that light scat-
tered by the brils is eliminated by destructive inter erence in
all directions other than the orward direction. T is situation
will hold as long as the axes o the collagen brils are arranged
in a regular lattice with a separation less than the wavelength o
light. It has been suggested, however, that the brillar arrange-
ment need not be in a per ect crystal lattice to maintain trans-
parency (Maurice, 1984), although disruption o short-range
order between brils will lead to increased scatter and a loss o
transparency.
16 PART 1 Int ro d uct io n
T e actors involved in the maintenance o collagen bril size
and spatial order are not ully understood. It has been proposed
that collagen bril diameters may be controlled by the incorpo-
ration o minor collagens (e.g. type V) into the predominantly
type I brils (Meek and Leonard, 1993) and that their spatial
separation is a unction o proteoglycan–collagen interactions
(Scott, 1991). Proteoglycans are a amily o glycoproteins that
consist o a protein core to which are attached sugar chains
o repeating disaccharide units termed glycosaminoglycans
(GAGs). T ese molecules are increasingly being recognized
as important prerequisites or transparency (Quantock and
Young, 2008; Hassell and Birk, 2010). Proteoglycans were origi-
nally classi ed according to their glycosaminoglycan composi-
tion; however, current nomenclature groups them into amilies
based on homologous sequences o amino acids in their protein
core. Corneal stromal proteoglycans are members o the small
leucine-rich amily, which are small enough to t in the space
between collagen brils. T e most prevalent glycosaminoglycan
in the cornea is keratan sulphate, which is ound in three types
o proteoglycan: lumican, keratocan and mimecan (Funder-
burgh et al., 1991; Funderburgh 2000). T e other type o corneal
proteoglycan is decorin, which contains a hybrid chondroitin
sulphate / dermatan sulphate side chain. Evidence rom several
sources has shown that lumican and decoran play important
roles in regulating collagen bril diameter and maintaining the
spacing between brils once ormed, which are essential or
transparency.
Hyd ration Control
T e state o corneal hydration is another important determi-
nant o corneal transparency (Bonanno 2012). T e hydrophilic
properties o the stroma are to a large part determined by pro-
teoglycans, which contribute to the xed negative charge o the
stroma and produce a passive gel swelling pressure through
electrostatic repulsion (Hodson, 1997). Physiologically, corneal
hydration is maintained at approximately 78%. I the cornea is
allowed to swell ±5% o this value, it begins to scatter signi cant
quantities o light (Hodson, 1997).
Maintenance o physiological corneal hydration is to a large
part dependent on the corneal endothelium, which possesses
both a barrier property and a metabolically driven pump. T e
endothelial barrier to the ree passage o molecules rom the
aqueous humour is ormed principally by ocal tight junctions
between adjacent endothelial cells. However, in contrast to
other barrier epithelia, these junctions are o low electrical resis-
tance and allow the passage o ions and small molecules. T is
leak is o set by the metabolically driven pumping o ions out o
the stroma by the endothelium, which maintains a transcellular
potential di erence (aqueous side negative) to balance stromal
swelling pressure (Maurice, 1984). Disruption o this osmotic
gradient will result in stromal uid imbibition.
T e speci c endothelial ion transport mechanisms respon-
sible or the maintenance o physiological hydration are not
ully understood. A simpli ed model representing our cur-
rent level o knowledge is represented in Fig. 2.13. T ere is
compelling evidence that a ux o bicarbonate ions is the pre-
dominant component o the endothelial ion transport system
(Hodson and Miller, 1976). Subsequent studies have identi ed
that Cl− transporters may also be important in maintaining the
pump (Bonanno 2012). T e bicarbonate is generated either
by a Na+ / HCO3− co-transporter located on the basolateral
plasma membrane or via the intercellular conversion o carbon
Fig . 2.13 Sche matic re p re se ntation o the corne al e nd othe lial p ump .
CA = carb onic anhyd rase ; TJ = tig ht junctio n.
dioxide by the enzyme carbonic anhydrase. Bicarbonate leaves
the cell via an apical bicarbonate ion channel. T e driving orce
or the bicarbonate ux is generated by a sodium–potassium
A Pase that resides on the basolateral endothelial membrane.
T e energy associated with subsequent sodium re-entry (via
Na+ / H + and Na+ / HCO3− transporters) is coupled to active
HCO3− ux (Hodson et al., 1991).
T e epithelium also contributes to corneal hydration con-
trol (Klyce and Beuerman, 1998). T e tight junctions between
super cial epithelial cells orm an e ective permeability barrier
to ions and polar solutes. For example, the anionic molecule
sodium uorescein does not penetrate an intact epithelium.
However, damage to the super cial cells allows uorescein to
enter the epithelium, with resulting corneal staining. In addition
to its barrier properties, the epithelium also possesses active ion
transport systems or Na+ and Cl−. As these pumps contribute
to the tonicity o the tear lm, it is likely that they are involved
in the maintenance o stromal hydration.
Re sp onse to O e d e ma
When corneas swell, light scattering increases, with an ensued
transparency loss due to the disruption o the regular collagen
matrix. T e collagen brils themselves swell very little and most
o the additional water goes into the inter brillar spaces. rans-
mission electron micrographs o oedematous corneas show
bril aggregation, with the result that large areas are devoid o
collagen brils (Stiemke et al., 1995). T ere is evidence that col-
lagen aggregation occurs as a result o loss o GAGs, which pre-
viously had maintained bre separation (Stiemke et al., 1995).
CO RNEAL EPITHELIAL WO UND HEALING
A smooth and intact corneal epithelium is necessary in order
or the cornea to maintain clear vision. However, due to its
exposed position the cornea is potentially vulnerable to a vari-
ety o external insults. It possesses several protective mecha-
nisms to avoid injury, but i tissue damage occurs it is capable
o an e ective wound-healing response (Gipson and Inatomi,
1995; Nishida and anaka, 1996). Corneal epithelial repair is a
complex process involving an orchestrated interaction between
cells and extracellular matrix, which is coordinated by a variety

o growth actors. T e process can be divided into three phases:
(1) initial covering o the denuded area by cell migration, (2)
cell proli eration to replace lost cells and (3) epithelial di eren-
tiation to re- orm the normal strati ed epithelial architecture.
Following a ull-thickness epithelial de ect, bronectin, an
adhesive glycoprotein, is synthesized and covers the sur ace o
the bared stroma where it serves as a temporary matrix or cell
migration. T e adhesion between bronectin and the epithe-
lium is mediated by integrin–matrix interactions (integrins are a
amily o cell sur ace receptors that bind to certain extracellular
matrix proteins). Several growth actors have been implicated in
the control o the wound-healing response, including epidermal
growth actor, trans orming growth actor beta, platelet-derived
growth actor and broblast growth actor (Gipson and Ina-
tomi, 1995). Growth actors, which are produced by a variety o
sources (e.g. ocular sur ace epithelia and the lacrimal gland), are
able to regulate the process o epithelial migration, proli eration
and di erentiation. T ere is evidence that epithelial–stromal
interactions play an important role in corneal wound healing
(Wilson, 2000). Epithelial injury triggers keratocyte apoptosis
(programmed cell death) in the anterior stroma, via the release
o apoptosis-inducing cytokines rom epithelial cells. Kerato-
cyte apoptosis subsequently triggers a wound-healing cascade,
which in uences epithelial repair.
Regeneration o the corneal epithelium is highly dependent
on the integrity o the limbus (Lavker et al., 2004). Cumulative
evidence indicates that a proportion o limbal basal epithelial
cells possess the properties o stem cells, which are ultimately
responsible or corneal epithelial replacement. Stem cells have
several unique characteristics: they are poorly di erentiated,
long lived and have a high capacity or sel -renewal. When these
cells divide, one o the daughter cells replenishes the stem cell
pool, whilst the other is destined to undergo urther cell divi-
sions be ore di erentiating. Such a cell is re erred to as a tran-
sient ampli ying cell. ransient ampli ying cells undergo several
rounds o cell division be ore ully di erentiating. T ese cells
play an important role in epithelial wound healing, where their
proli erative capacity is increased by shortening cycle times and
increasing the number o times that the transient ampli ying
cells can divide be ore maturation.
The O cular Ad ne xa
T e ocular adnexa are those structures that support and pro-
tect the eye, and include the eyelids, conjunctiva and lacrimal
system. T ey play an important role in the ormation o the pre-
ocular tear lm and collectively de end the eye against antigenic
challenge.
EYELIDS
T e eyelids are two mobile olds o skin that per orm several
important unctions: they act as occluders that shield the eyes
rom excessive light, and through their re ex closure they a ord
protection against injury. T e lids also orm a precorneal tear
lm o uni orm thickness during the upturn phase o each
blink. T e action o blinking is also important or tear drainage.
Gross Anatomy
T e eyelids are joined at their extremities, termed ‘the canthi’,
and when the eye is open, an elliptical space, the palpebral s-
sure, is ormed between the lid margins. In the adult, the length
2 Ant e rio r Eye 17
Fig . 2.14 Sur ace anatomy o the e ye lid s. (Ad ap te d rom Bron, A. J.,
Trip athi, R. C. & Trip athi, B. (1997). Wol ’s Anatomy o the Eye and O rb it
(8th e d .). Lond on: Chap man and Hall.)
o the ssure is approximately 30–31 mm, with a vertical height
o 10–11 mm. In the primary position, the upper lid, which is
the larger and more mobile o the two, typically covers approxi-
mately the upper third o the cornea, whilst the lower lid is level
with the in erior corneal limbus (Fig. 2.14). Important di er-
ences in eyelid anatomy exist between Asian and Caucasian eyes
(Saonanon, 2014). T e most obvious eature o the Asian eye is
the absent or very low lid old and uller upper eyelid.
T e eyelid margins are about 2 mm thick rom ront to back.
T e posterior quarter consists o conjunctival mucosa and the
anterior three-quarters is skin. T e junction between the two is
re erred to as the mucocutaneous junction. T ere has recently
been a renewed interest in the marginal zone o the human eyelid,
with the identi cation o the role o the inner lid border, termed
the ‘lid-wiper’ owing to the analogy to a windscreen wiper, in
the distribution o the tear lm (Knop et al., 2011a, 2012). wo
or three rows o eyelashes (cilia) arise rom the anterior border
o the lid margins. T ese are longer and more numerous in the
upper lid. T e lashes receive a rich sensory nerve supply, and
their sensitivity provides an e ective alerting mechanism.
T e meibomian (tarsal) gland ori ces emerge just anterior
to the mucocutaneous junction (Fig. 2.15). About 30–40 glands
open onto the upper margin, and slightly ewer (20–40) onto
the lower. On eversion o the lids the yellowish meibomian
acini are visible as yellow clusters through the tarsal conjunc-
tiva (Bron et al., 1991; Knop et al., 2011b). Meibomian glands
can be more clearly visualized using in rared meibography, and
instruments that use this method are now commercially avail-
able (Srinivasan et al., 2012) (Fig. 2.16). At the medial angle,
the eyelid margins enclose a triangular space – the lacus lacri-
malis – which contains the plica semilunaris and the caruncle.
Lacrimal papillae are small elevations located 5–6 mm rom the
medial canthal angle, which contains a small aperture (punc-
tum) that is the opening to the lacrimal drainage system.
Muscle s of the Eye lid s
Movements o the eyelids are governed by the coordinated
action o several muscles.
Orbicularis Oculi. T e orbicularis oculi is the sphincter muscle
o the eyelids, and can anatomically be divided into two main
divisions: the palpebral and the orbital (Fig. 2.17). Fibres o the
palpebral division arise rom the medial palpebral ligament
and arc across the eyelids in a series o hal -ellipses, meeting at
the lateral canthus to orm a lateral raphe. T e lateral palpebral
18 PART 1 Int ro d uct io n
Fig . 2.15 (A) Sche matic re p re se ntation o the e ye lid marg in. mcj = mu-
cocutane ous junction. (B) Gross ap p e arance o the e ye lid marg in.
O p e ning s o the me ib omian g land s are cle arly visib le (arrow). (Ad ap te d
rom Bron, A. J., Trip athi, R. C. & Trip athi, B. (1997). Wol ’s Anatomy o
the Eye and O rb it (8th e d .). Lond on: Chap man and Hall.)
Fig . 2.16 Normal me ib omian g land s o the up p e r tarsus (top ) and low-
e r tarsus (b ottom) o a 38-ye ar-old woman, imag e d using no n-invasive
in rare d me ib og rap hy. (Imag e courte sy o Re iko Arita.)
Fig . 2.17 Sche matic re p re se ntation o the d ivisions o the orb icularis
oculi and the rontalis. a = p re tarsal; b = p re se p tal; c = orb ital; d = ronta-
lis. (Ad ap te d rom Bron, A. J., Trip athi, R. C. & Trip athi, B. (1997). Wol ’s
Anatomy o the Eye and O rb it (8th e d .). Lond on: Chap man and Hall.)
ligament also acts as an anchor point. T e palpebral division
can be urther subdivided into marginal, pretarsal and preseptal
parts. T e marginal part (pars ciliaris), which is also known as
Riolans muscle, is responsible or maintaining the apposition
o the lid to the cornea during lid closure. A third part o the
muscle (pars lacrimalis) is closely associated with the lacrimal
out ow pathway. T e pars lacrimalis (also known as Horner’s
muscle) encloses the canaliculi and provides attachments to the
lacrimal sac and its associated ascia.
T e orbital part o the orbicularis oculi lies outside the palpe-
bral division and extends or some distance beyond the orbital
margins. Muscle bres arise predominantly rom bone at the
medial orbital rim and appear to sweep around the lids without
interruption as a series o complete ellipses. However, studies
have shown that the muscle bres o the orbital and palpebral
division o the orbicularis are relatively short (0.4–2.1 mm) and
overlapping (Lander et al., 1996). T e regional divisions o the
orbicularis also show a unctional distinction. T e action o the
palpebral part o the muscle is to produce the re ex or voluntary
closure o the lids during blinking. Contraction o the orbital
division produces the orcible closure o the lids that occurs in
sneezing or in response to a pain ul stimulus.
Levator Palpebrae Superioris. T e levator palpebrae superioris
is primarily responsible or elevating the upper lid during
blinking and or maintaining an open palpebral aperture. T e
levator palpebrae arises rom the lesser wing o the sphenoid,
above and anterior to the optic canal, and runs orward along
the roo o the orbit above the superior rectus be ore terminating
anteriorly in a an-shaped tendon (aponeurosis). Some bres
are attached to the anterior sur ace o the tarsal plate, whilst the
remainder pass between ascicles o the orbicularis (Fig. 2.18).
T e superior palpebral sulcus orms at the upper border o the
attachment to the orbicularis.
Superior and Inferior Tarsal Muscles (of Müller). T ese
smooth muscles arise rom the lower border o the levator in the
upper lid and the in erior rectus in the lower lid, and insert into
the orbital margins o the tarsal plates. T e role o the superior
tarsal muscle is to assist the levator in maintaining the width
o the palpebral aperture. A mild degree o ptosis results rom
damage to its sympathetic nerve supply (Horner’s syndrome).

Fig . 2.18 Diag ram showing the re lations o the le vator p alp e b rae
sup e rioris. a = le vator ap one urosis; tm = sup e rior tarsal muscle (o Mül-
le r); t = tarsal p late ; s = orb ital se p tum. (Ad ap te d rom Gray, H., Bannis-
te r, L. H., Be rry, M. M. & Williams, P. L. (1995) Gray’s Anatomy: The Ana-
tomical Basis o Me d icine and Surg e ry (38th e d .). Ed inb urg h: Churchill
Living stone .)
Control of Eye lid Move me nts
Movements o the eyelids occur through the coordinated action
o several muscles – the levator palpebrae, tarsal muscles, the
orbicularis oculi and the rontalis. T e elevation o the upper lid
and the control o its vertical position are mediated principally
by the levator. In vertical gaze, lid position and eye movements
are closely linked. During elevation the state o contraction o
the levator is varied to maximize visibility. In extreme upgaze,
lid retraction is augmented by the action o the rontalis, which
elevates the eyebrows. In downgaze, coordinated lid move-
ments similarly occur through levator relaxation. In periodic
and re ex blinks, the levator is spontaneously inhibited prior to
orbicularis contraction in lid closure. Similarly, in lid opening
the orbicularis relaxes, ollowed by contraction o the levator.
Spontaneous eye-blink activity is in uenced by both central and
peripheral actors ( subota, 1998).
Compared with the upper lid, the lower lid is relatively
immobile and has no counterpart to the levator palpebrae. T e
depression o the lower lid that occurs in downgaze is due to the
attachment o the sheaths o the in erior oblique and in erior
rectus muscles to the tarsal plate via a brous extension.
Microscop ic Anatomy
T e histological appearance o the upper and lower lids is similar,
and in sagittal section the ollowing six tissue layers can be resolved:
skin, subcutaneous connective tissue, muscle layer, submuscular
connective tissue, tarsal plate and palpebral conjunctiva (Fig. 2.19).
T e eyelid skin is thin and very elastic. It is continuous with
the palpebral conjunctiva at the lid margin, and keratinization
is maintained up to this mucocutaneous junction. T e subcu-
taneous connective tissue is composed o a loose areolar tissue
and contains hair ollicles and associated glands. T e muscle
layer consists o striated muscle bres o the orbicularis oculi,
which are arranged in bundles ( ascicles) separated by con-
nective tissue. T e orbicularis extends throughout the lid. T e
marginal part o the muscle (Riolan’s muscle) is separated rom
the pretarsal portion by connective tissue that contains the eye-
lash ollicles. T e loose submuscular connective tissue layer lies
between the orbicularis and the tarsal plate and contains the
major nerves and vessels o the lid.
T e tarsal plates (tarsi) are composed o dense brous con-
nective tissue and provide support and determine lid shape.
2 Ant e rio r Eye 19
Fig . 2.19 Sag ittal se ction throug h the up p e r lid . TP = tarsal p late ;
O O c = orb icularis oculi; R = Riolan’s muscle ; EF = e ye lash ollicle s;
PC = p alp e b ral conjunctiva; ES = e ye lid sur ace .
T ey are anchored to the orbital margins by the medial and lat-
eral palpebral ligaments. Each tarsus is approximately 25 mm
long and 1–2 mm thick. T e upper tarsus is semioval with a
height o 11 mm at its midpoint, whereas the in erior tarsus is
narrower (4 mm in height). T e posterior sur ace o the eyelid
is lined by the palpebral conjunctiva, which is rmly adherent
to the underlying tarsal plate.
Gland s of the Eye lid s
Meibomian Glands. T e tarsal plates contain the acini and ducts
o the meibomian (tarsal) glands. Ducts are vertically oriented with
respect to the lid margins, with multiple secretory acini that open
laterally onto each duct. T e glands occupy nearly the ull length
and width o each tarsus, and are ewer and shorter in the lower
lid. Histologically, the acini are lined by a layer o undi erentiated
basal cells that divide, and cells are displaced rom the basement
membrane. As they progress towards the duct they gradually
enlarge and develop lipid droplets in their cytoplasm (Fig. 2.20).
Ultimately, cell membranes rupture and cellular debris, together
with the lipid product, is discharged into the duct.
T e stimulus or meibomian gland secretion is unclear.
Although a modest autonomic innervation o the meibomian
glands has been demonstrated, there is still some doubt regard-
ing a neuromodulation o glandular secretion; it is likely that the
principal control o the glands is hormonal, and both androgens
and oestrogens have been shown to regulate meibomian secre-
tion (Sullivan et al., 2000; Knop et al., 2011b). A long ductal
system carries the secretion to the lid margin, and the compres-
sive action o the palpebral division o the orbicularis oculi on
the meibomian ducts acilitates the ow o lipid and its eventual
delivery onto the lid margins.
20 PART 1 Int ro d uct io n
Fig . 2.20 Histolog ical se ction showing me ib omian g land acini. Se cre -
tory ce lls d e g e ne rate (aste risk) as the y ap p roach the d uct (D).
Fig . 2.21 Histolog ical se ction throug h the ciliary zone o the e ye lid .
Gland s o Ze is (Z) d ischarg e the ir conte nts into an e ye lash ollicle (EF),
which contains the re mnants o an e ye lash. M = g land o Moll.
Glands of Zeis and Moll. Ciliary glands o Zeis and Moll are
ound in association with eyelash ollicles ( akahashi et al.,
2013) (Fig. 2.21). Zeis glands are unilobular sebaceous glands
that open directly into the ollicle. T e unction o their oily
secretion is to lubricate the lashes to prevent them rom drying
out and becoming brittle. Glands o Moll are modi ed sweat
glands (apocrine) consisting o an unbranched spiral tubule.
T e exact unction o these glands is unclear, although their
secretion is rich in IgA, which suggest a role in the immune
de ence o the ocular sur ace (Stoeckelhuber et al., 2003).
Blood and Ne rve Sup p ly
Nerves of the Eyelids. T e levator palpebrae and orbicularis
oculi muscles are innervated by the oculomotor and acial
nerves, respectively. T e sensory supply o the upper lid
derives rom branches o the ophthalmic nerve (supraorbital,
supratrochlear and lacrimal). T e supply to the lower lid comes
rom branches o the maxillary nerve (zygomatic, in raorbital).
Blood and Lymphatic Supply to the Eyelids. T e arterial
supply derives rom branches o the ophthalmic, lacrimal
and in raorbital arteries, which contribute to two palpebral
arcades in the upper lid and one in the lower. Branches rom
these arcades supply the skin, orbicularis, tarsal glands and
Fig . 2.22 Sche matic re p re se ntation o a mid -sag ittal se ction throug h
the e ye lid and conjunctival sac showing the d i e re nt conjunctival re -
g ions. M = marg inal; T = tarsal; O = orb ital; B = b ulb ar; L= limb al; F = or-
nical.
Fig . 2.23 Static d ime nsions o the conjunctival sac in millime tre s.
M = me d ial canthus. (Ad ap te d ro m Ehle rs, N. (1965). O n the size o the
co njunctival sac. Acta O p hthalmol., 43, 205–210.)
palpebral conjunctiva. Veins o the eyelids empty into veins o
the orehead and temple, and some empty into the ophthalmic
vein. Lymphatics drain to the preauricular and submandibular
lymph nodes.
THE CO NJ UNCTIVA
Gross Anatomy
T e conjunctiva is a thin transparent mucous membrane that
extends rom the eyelid margins anteriorly, providing a lining to
the lids, be ore turning sharply upon itsel to orm the ornices,
rom where it is re ected onto the globe, covering the sclera up
to its junction with the cornea. It thus orms a sac that opens
anteriorly through the palpebral ssure. T e conjunctiva is con-
ventionally divided into the ollowing regions: marginal, tarsal,
orbital (these three collectively orm the palpebral conjunctiva),
bulbar and limbal (Fig. 2.22).
T e static dimensions o the conjunctival sac in the primary
position are illustrated in Fig. 2.23 (Ehlers, 1965). T e marginal
zone extends rom a line immediately posterior to the openings
o the tarsal glands and passes around the eyelid margin, rom
where it continues on the inner sur ace o the lid as ar as the
subtarsal old (a shallow groove that marks the marginal edge
o the tarsal plate). T e tarsal conjunctiva is highly vascular
and is rmly attached to the underlying brous connective tis-
sue. From the convex border o the tarsal plate, the orbital zone
 2 Ant e rio r Eye 21

Fig . 2.24 Hig h-p owe r slit-lamp vie w o the conjunctival p alisad e s o
Vog t (aste risks) at the lowe r limb us.

extends as ar as the ornices. Over this region the conjunctiva is

more loosely attached to underlying tissues, and so readily olds.
Elevations o the conjunctival sur ace in the orm o papillae
and lymphoid ollicles are commonly observed in this region.
T e transparency o the bulbar conjunctiva readily permits
the visualization o conjunctival and episcleral blood vessels.
Here, the conjunctiva is reely movable owing to its loose attach-
ment to enon’s capsule (the ascial sheath o the globe). As the
bulbar conjunctiva approaches the cornea, its sur ace becomes
smoother and its attachment to the sclera increases. T e limbal
conjunctiva extends approximately 1–1.5 mm around the cornea.
Its junction with the cornea is ill de ned, particularly in the ver-
tical meridian, owing to a variable degree o conjunctival / scleral
overlap. T e limbus has a rich blood supply, and in the majority
o individuals a radial array o connective tissue elevations – the
palisades o Vogt – can be seen adjacent to the corneal margin
(Fig. 2.24). T e palisades are most prominent in the vertical
meridian, and their visibility is enhanced in pigmented eyes.
Microscop ic Anatomy
In histological section, two distinct layers can be resolved: an
epithelium containing a variable number o goblet cells, and a
vascular stroma that consists o a super cial lymphoid layer and
a deep brous layer (Fig. 2.25). T e appearance o the conjunc-
tiva shows a marked regional variability.
Epithelium. In the marginal zone, the epithelium is strati ed
and squamous with relatively ew goblet cells, although this has
recently been disputed ollowing the description o intracellular
crypts lined with goblet cells lying deep within the epithelium in
the region o the so-called ‘lid wiper’ region (Knop et al., 2012).
It has been suggested that a subpopulation o epithelial cells that
lie close to the mucocutaneous junction may be acting as stem
cells or the palpebral conjunctiva (Wirtscha er et al., 1999).
Approaching the tarsus, the epithelium thins to 2–3 layers o
cuboidal cells with scattered goblet cells. T e epithelium o the
orbital zone is slightly thicker (2–4 cells) with more numerous
goblet cells. T e number o goblet cells declines over the bulbar
conjunctiva and at the limbus the epithelium is again strati ed
squamous, and goblet cells are absent. T e limbus contains a
Fig . 2.25 Histolog ical se ction throug h the b ulb ar conjunctiva. E = e p i-
the lium; S = stro ma. Gob le t ce lls can b e se e n in the e p ithe lium (arrows).
The stroma can b e re solve d into an ad e noid laye r (arrowhe ad ) and a
d e e p b rous laye r (aste risk).
Fig . 2.26 Histolog ical se ction throug h the p alisad e re g ion. Conne c-
tive tissue rid g e s can b e se e n p roje cting into the ove rlying e p ithe lium
(arrows).
unique array o connective tissue ridges (the palisades o Vogt),
which project into the overlying epithelium (Fig. 2.26). Clinical
and experimental evidence suggests that the palisades are the
repositories o stem cells and there ore act as the regenerative
organ o the corneal epithelium (Dua and Azuara-Blanco,
2000). T e conjunctival epithelium additionally contains several
non-native cell types, including dendritic cells, melanocytes and
lymphocytes.
Goblet and Other Secretory Cells. Goblet cells provide the
mucous component o the tear lm. T ey arise in the basal
cell layers and migrate to the sur ace, there becoming ully
di erentiated. Mature goblet cells are larger than the surrounding
epithelial cells and contain a peripherally placed nucleus. T e
cytoplasm is packed with membrane-bound secretory granules
that discharge rom the apical sur ace in an apocrine manner.
T e number o goblet cells shows a marked regional variation
in density (Kessing, 1968) (Fig. 2.27), and these cells are
occasionally seen lining intraepithelial crypts (o Henle).
22 PART 1 Int ro d uct io n

Fig . 2.27 Diag ram showing the re g ional variation in g ob le t ce ll d e nsi-

ty. Gob le t ce ll d e nsity is g re ate st ove r the caruncle , p lica se milunaris and
in e rior nasal p alp e b ral conjunctiva. (Ad ap te d rom Bron, A. J., Trip athi,
R. C. & Trip athi, B. (1997). Wol ’s Anatomy o the Eye and O rb it (8th e d .).
Lond on: Chap man and Hall. Re p rod uce d ro m Bron, 1997.)
Fig . 2.28 Histolog ical se ction throug h a lymp hoid ollicle (F). Note the
mod i cation o the ove rlying e p ithe lium (aste risk).
T e apices o many sur ace epithelial cells o the conjunc-
tiva contain numerous carbohydrate-containing secretory
vesicles, which are seen to migrate to the cell sur ace where
they use with the plasma membrane (Dilly, 1985). It is likely
that this represents a mechanism or recycling the cell sur-
ace glycocalyx rather than a secondary source o secretory
mucin.

Conjunctival Stroma. T e conjunctival stroma (substantia

propria) is variable in thickness. It can be resolved into
two distinct layers: a super cial adenoid layer and a deeper
brous layer (see Fig. 2.25). T e adenoid layer contains
numerous lymphocytes with local accumulations in the orm
o lymphoid ollicles (Fig. 2.28). Follicles represent aggregates
o predominantly B cells, which orm part o the so-called
conjunctiva-associated lymphoid tissue (Knop and Knop,
2005). T e adenoid layer also contains a large number o mast
cells, which play a major role in ocular allergy (McGill et al.,
1998). T e deep brous layer is generally thicker than the
adenoid layer and contains the majority o conjunctival blood
vessels and nerves.
Inne rvation and Blood Sup p ly
Nerves. he conjunctiva receives nerves rom sensory,
sympathetic and parasympathetic sources. Sensory nerves,
which are trigeminal in origin, reach the conjunctiva via
branches o the ophthalmic nerve. he principal unction
o these ibres is to equip the conjunctiva with the ability
to detect a variety o sensations – or example, touch, pain,
warmth and cold. Sensory nerve terminals include both
ree (unspecialized) nerve endings and the more complex
corpuscular endings (classically re erred to as Krause end
bulbs) (Lawrenson and Ruskell, 1991). Conjunctival blood
vessels receive a dual autonomic innervation. Parasympathetic
ibres issuing rom the pterygopalatine ganglion and
sympathetic ibres rom the superior cervical ganglion
are responsible or vasodilation and vasoconstriction,
respectively.
Fig . 2.29 Hig h-p owe r slit-lamp p hotog rap h showing the limb al vascu-
lar arcad e s. (Courte sy o Eric Pap as.)
Blood Vessels and Lymphatics. T e arterial supply derives
rom two sources: palpebral branches o the nasal and lacrimal
arteries, and anterior ciliary arteries.
Palpebral vessels serve two vascular arcades within the eye-
lid. T e in erior (marginal) arcade sends branches through the
tarsal plate to the eyelid margin and tarsal conjunctiva. T e
superior (palpebral) arcade supplies the tarsal, orbital, ornix
and bulbar conjunctiva. T e limbal zone, in contrast, is served
by anterior ciliary arteries. T e anterior ciliary arteries travel
along the tendons o the rectus muscles and give o branches
at episcleral level prior to dipping down into the sclera to link
with the major iridic circle. Episcleral branches pass orward
and loop back a ew millimetres short o the cornea to become
conjunctival vessels. Forward extensions o these vessels orm
the limbal arcades (limbal loops), which are a complex net-
work o ne capillaries (Fig. 2.29). Conjunctival veins are more
numerous than arteries. T ey can be readily di erentiated rom
arteries owing to their larger calibre, darker colour and more
tortuous path.

Fig . 2.30 Late ral vie w o the orb it showing the position o the lacrimal
g land. The levator ap oneurosis (LA) p artially divid e s the g land into an
orb ital (OD) and palpe bral (PD) d ivision. (Adapted rom Kron eld, P. C.,
McHug h, S. L. & Polyak, S. L. (1943). The Human Eye in Anatomical
Transp are ncie s. Roche ste r, NY: Bausch & Lomb .)
Functional Consid e rations
T e conjunctiva contributes the mucin component o the pre-
ocular tear lm and plays an important role in the de ence o
the ocular sur ace against microbial in ection. Mucins are a
amily o high-molecular-weight glycoproteins that include
membrane-bound and secretory varieties (Cor eld et al., 1997;
Gipson and Inatomi, 1997; Hodges and Dartt, 2013). Goblet
cells are the primary source o secretory mucin, whilst sur-
ace epithelial cells o both the conjunctiva and cornea possess
mucin-like molecules within their glycocalyx. T e conjunctiva
also orms part o a common mucosal de ence system, which
is an important component o the de ence o the human body
against microorganisms (McClellan, 1997; Knop and Knop,
2005). T e conjunctiva possesses the immunological capacity
or antigen processing, and cell-mediated and humoral immu-
nity. Humoral immunity is provided by speci c antibodies (par-
ticularly immunoglobulin A [IgA]) produced by trans ormed B
cells (plasma cells) in the stroma. lymphocytes orm the basis
o cell-mediated immunity.
LACRIMAL SYSTEM
T e lacrimal apparatus provides or the production and main-
tenance o the preocular tear lm. T e normal unction o this
system is essential or the integrity o the ocular sur ace and the
provision o a smooth re ractive sur ace. T e lacrimal apparatus
comprises a secretory system that includes the main and acces-
sory lacrimal glands, and a drainage system that consists o the
paired puncta and canaliculi, the lacrimal sac and the nasolac-
rimal duct.
Lacrimal Gland
Gross Anatomy. T e main lacrimal gland is the key provider
o the aqueous component o the tears. T e gland is located in a
shallow depression o the rontal bone behind the superolateral
orbital rim (Fig. 2.30). It is partially split by the aponeurosis
o the levator palpebrae into an upper larger orbital lobe and
2 Ant e rio r Eye 23
Fig . 2.31 Low-p owe r lig ht microg rap h o the lacrimal g land . Acini are
arrowe d . Ad ip ose conne ctive tissue (aste risks) e xte nd s across the g land .
Fig . 2.32 Ele ctron microg rap h o p art o a lacrimal acinus showing
lig ht and d ark se cre tory ce lls.
a lower palpebral lobe, which can o en be visualized through
the conjunctiva upon lid eversion (Bron, 1986). T e gland is
pinkish in colour, with a lobulated sur ace. Between 6 and 12
ducts leave the gland through the palpebral lobe and discharge
into the conjunctival sac at the upper lateral ornix.
Microscopic Anatomy. T e lacrimal gland is tubuloacinar in
orm (Fig. 2.31). Its secretory units (acini) contain secretory
cells surrounded by myoepithelial cells (Ruskell, 1975). Acinar
secretory cells show extensive olding o their plasma membrane
and apical microvilli. Adjacent cells are linked by tight junctions
that restrict di usion between cells. T e most prominent eature
o these cells is the presence o abundant secretory granules.
wo principal secretory cell subtypes have been identi ed on
the basis o their granule content (Fig. 2.32). T e majority o
cells contain dark granules (dark cells), with a smaller number
o cells containing light granules (light cells). T e unctional
signi cance o this heterogeneity is uncertain at present. Ducts
consist o a single layer o cuboidal cells that lack secretory
granules. Myoepithelial cells are dendritic cells that are closely
associated with the perimeter o acini and ducts. It is likely that
these contractile cells play a role in the expulsion o tears rom the
gland. T e interstices o the gland contain numerous blood vessels
and nerves. A large population o immune cells (particularly IgA-
secreting plasma cells) are also ound between acini.
24 PART 1 Int ro d uct io n
Fig . 2.33 Diag ram showing the role o the g astrointe stinal tract g e n-
e rating sp e ci c immunog lo b ulin A (Ig A) in the lacrimal g land . Antig e ns
which challe ng e the ocular sur ace ultimate ly d rain to the g astrointe s-
tinal (GI) tract whe re the y stimulate B ce lls in Pe ye r’s p atche s (g ut-as-
sociate d lymp hoid tissue ). Se nsitize d B ce lls the n p ass to the lacrimal
g land via the circulation. SC = se cre tory comp one nt. (Ad ap te d rom Al-
lansmith, M. R. (1992). The Eye and Immunolog y. Maryland He ig hts, MO :
Mosb y. Cop yrig ht Else vie r 2002.)
Blood and Nerve Supply. T e arterial supply to the lacrimal
gland is provided by the lacrimal artery, which enters the posterior
border o the gland. Venous drainage occurs via the lacrimal
vein. A rich autonomic innervation includes secretomotor
(parasympathetic) bres that issue rom the pterygopalatine
ganglion and sympathetic (vasomotor) bres rom the carotid
plexus. T e lacrimal nerve traverses the gland to provide a sensory
innervation to the conjunctiva and lateral aspect o the eyelid.
Accessory Lacrimal Glands. Numerous small accessory
lacrimal glands, which include the eponymous glands o
Wol ring and Krause, are ound within the conjunctival stroma.
T ey have a particular predilection or the upper ornix and
above the tarsal plate, and, on the basis o proportion o total
lacrimal tissue, it has been estimated that they contribute
5–10% o aqueous tear volume. Structurally, they have a similar
appearance to the lacrimal gland proper. However, true acini are
absent and glands consist o elongated tubules that connect with
ducts opening onto the conjunctival sur ace (Sei ert et al., 1993).
Functional Considerations. In addition to its role as the principal
provider o the aqueous phase o the tear lm, the lacrimal gland
is also a major component o the ocular sensory immune system,
which acts as the rst line o de ence against microbial in ection
(Sullivan and Sato, 1994). T e secretory immune system is
mediated through secretory IgA. T e lacrimal gland is the main
source o tear IgA and the gland contains a large number o IgA-
producing plasma cells. T e mechanism by which an antigenic
challenge o the ocular sur ace induces a lacrimal antibody
response is not ully understood. However, as the administration
o an antigen by a gastrointestinal route raises speci c IgA levels
in tears, one suggested mechanism is that ocular antigens – a er
drainage through the nasolacrimal duct – stimulate B cells in
gut Peyer’s patches. T ese sensitized B cells then populate the
lacrimal gland where they trans orm into plasma cells (Fig. 2.33).
Fig . 2.34 Illustration o the lacrimal d rainag e syste m. C = canaliculi;
LS = lacrimal sac; P = p unctum; NLD = nasolacrimal d uct. (Ad ap te d rom
Kron e ld , P. C., McHug h, S. L. & Polyak, S. L. (1943). The Human Eye in
Anatomical Transp are ncie s. Roche ste r, NY: Bausch & Lomb .)
It has been demonstrated that the lacrimal gland also
secretes into the tears growth actors that are important or the
maintenance o the ocular sur ace and epithelial wound healing
(P ug elder, 1998). Prominent amongst these growth actors are
epidermal growth actor and trans orming growth actor beta.
Lacrimal Drainag e Syste m
ears collect at the medial canthal angle, where they drain into
the puncta o the upper and lower lids. Each punctum is a small
oval opening approximately 0.3 mm in diameter that is located
at the summit o an elevated papilla. From each punctum the
canaliculus passes rst vertically or about 2 mm and then turns
sharply to run medially or about 8 mm (Fig. 2.34). At the angle,
a slight dilation, the ampulla, can be seen. T e canaliculi con-
verge towards the lacrimal sac, usually orming a common can-
aliculus be ore entry. T e lacrimal sac occupies a ossa ormed
by the maxillary and lacrimal bones. It measures 1.5–2.5 mm in
diameter and approximately 12–15 mm in vertical length. From
the lacrimal sac tears drain into the nasolacrimal duct, which
extends or about 15 mm, passing through a bony canal in the
maxillary bone, to an opening in the nose beneath the in erior
nasal turbinate. A old o mucosa is o en observed at the ter-
mination o the duct: this has been termed ‘the valve o Hasner’,
although there is no strong evidence that it unctions as a valve.
T e process o tear drainage is an active process mediated
by the contraction o the orbicularis during blinking (Doane,
1981). ears enter the canaliculi principally by capillary action.
During the early part o the blink the puncta are occluded as
the orbicularis urther contracts. T e canaliculi and lacrimal
sac are also compressed, orcing uid into the nose. An alterna-
tive hypothesis has been proposed whereby orbicularis contrac-
tion dilates the sac, creating a negative pressure, which draws
in the tears rom the canaliculi (Jones, 1961). An investigation
by Paulsen et al. (2000) described a vascular plexus embedded
in the wall o the lacrimal sac and duct that may in uence tear
out ow. It is postulated that opening and closing o the lumen o
 2 Ant e rio r Eye 25

TABLE Physical Pro p e rt ie s o f t he Pre o cular Te ar

2.2 Film
Parame t e r Value
O smolarity 302 (± 6.3) mO sm/l
pH 7.45
Thickne ss 3 µl
Volume 7.0 (± 0.2) µl
Rate of p rod uction
Unstimulate d 1–2 µl / min
Stimulate d >100 µl / min
Re fractive ind e x 1.336

the lacrimal passages can be achieved by regulating blood ow

within this plexus.

The Pre o cular Te ar Film

FUNCTIO N AND PRO PERTIES O F THE
PREO CULAR TEAR FILM
T e tear lm is a complex uid that covers the exposed parts o the
ocular sur ace ramed by the eyelid margins. T e physical charac-
teristics o this uid are summarized in able 2.2. Classically, the
tear lm has been regarded as a trilaminar structure with a super-
cial lipid layer secreted by the meibomian glands, which overlies
an aqueous phase derived rom the main and accessory lacrimal
glands, and an inner mucinous layer consisting o membrane-
spanning mucins o the ocular sur ace epithelium and secretory
mucins produced mainly by conjunctival goblet cells. T e tear
lm per orms several important unctions, which can be broadly
classi ed as optical, metabolic support, protective and lubrication.
By smoothing out irregularities o the corneal epithelium, the
tear lm creates an even sur ace o good optical quality that is re-
ormed with each blink. T e air–tear inter ace orms the principal
re ractive sur ace o the optical system o the eye and provides two-
thirds (43 D) o its total re ractive power. As the cornea is avascular Fig . 2.35 Schematic rep rese ntation o the orbital g lands, which contrib -
ute the various components o the preocular tear lm. (Adapted rom Dartt,
it is dependent on the tear lm or its oxygen provision. When the D. A. (1992). Physiology o tear production. In M. A. Lemp & R. Marquardt
eye is open the tear lm is in a state o equilibrium with the oxygen (ed s) The Dry Eye: A Comprehensive Guide. Berlin: Springer-Verlag.)
in the atmosphere, and gaseous exchange takes place across the
tear inter ace. T e constant turnover o the tear lm also provides
a mechanism or the removal o metabolic waste products. (i.e. in response to strong physical or emotional stimulation) is
ears play a major role in the de ence o the eye against mediated by the main lacrimal gland. However, Jordan and Baum
microbial colonization. T e washing action o the tear uid (1980) questioned the concept o basic and re ex secretion, and
reduces the likelihood o microbial adhesion to the ocular sur- suggested that it is more accurate to think o tear output as a con-
ace. Moreover, the tears contain a host o protective antimicro- tinuum, whereby the rate o production is proportional to the
bial proteins. T e tear lm acts as a lubricant, smoothing the degree o sensory or emotive stimulation (Dartt, 2009). T is con-
passage o the lids over the corneal sur ace and preventing the cept would also mean that a unctional distinction between main
transmission o damaging shearing orces. o acilitate this, tear and accessory lacrimal glands, in terms o basal and re ex tear
uid displays non-Newtonian behaviour with respect to shear production, is unnecessary. Rather, it is more likely that tear ow
( i any, 1991). Newtonian uids maintain a constant viscosity is the combination o contributions rom both glands, although
with increasing shear rates. By contrast, tear uid has a rela- the output rom the accessory glands alone is suf cient to main-
tively high viscosity between blinks to aid stability, and with tain a stable tear layer (Maitchouk et al., 2000).
increasing shear rates during the blink process the viscosity alls
dramatically, thereby easing the movement o the lids over the SO URCES AND CO MPO SITIO N
ocular sur ace.
ears are composed o a complex secretion that combines the
Te ar Prod uction products o several glands (Fig. 2.35). Although the precise com-
Jones (1966) rst used the terms ‘basic (basal)’ and ‘re ex’ to position o tear uid varies with collection method, ow rate and
describe tear ow. He proposed that the accessory lacrimal glands time o day, it can be considered as a watery secretion containing
were the basic (minimal ow) secretors, and that re ex secretion electrolytes and proteins, with lesser amounts o lipid and mucin.
26 PART 1 Int ro d uct io n

is a constitutively secreted lacrimal protein whose rate o secre-

TABLE Bio che mical Co mp o sit io n o f t he Pre o cular tion is independent o ow rate. During sleep, the levels o IgA
2.3 Te ar Film increase as secretory IgA production continues and as acinar
Co mp o ne nt Co nce nt rat io n secretion declines (Sack et al., 1992). IgA plays an important
role in the de ence o the ocular sur ace against microbial in ec-
ELECTRO LYTES* tion by preventing bacterial and viral adhesion, and inactivating
Na + 135 mEq / l
Cl− 131 mEq / l
bacterial toxins. Other immunoglobulins (e.g. IgG and IgM) are
K+ 36 mEq / l present in tears at much lower levels.
HCO 3 − 26 mEq / l Lysozyme, lacto errin and lipocalin, in contrast, originate
Ca 2+ 0.46 mEq / l rom acinar cells and their rate o secretion roughly matches
Mg 2+ 0.36 mEq / l ow rate. Lysozyme is a well-known bacteriolytic protein that
MAJ O R PRO TEINS* has the ability to lyse the cell wall o several Gram-positive bac-
Lysozyme 2.07 g / l teria. Lacto errin serves an important bacteriostatic unction by
Se cre tory Ig A 3.69 g / l binding iron and making it unavailable or bacterial metabo-
Lactofe rrin 1.65 g / l lism. It also acts as a ree radical scavenger, thereby reducing
Lip ocalin 1.55 g / l
Alb umin 0.04 g / l ree-radical-mediated cell damage ( i any, 1997). Lipocalins
Ig G 0.004 g / l are a amily o lipid-binding proteins with an af nity or a broad
LIPIDS† array o lipids, including atty acids, phospholipids and choles-
Wax e ste rs 41% terol. It has been suggested that tear lipocalins act as scavengers
Chole ste ryl e ste rs 27.3% or a wide range o meibomian lipids, which could spill onto
Polar lip id s 14.8% the corneal sur ace and perturb its wettability (Glasgow et al.,
Hyd rocarb ons 7.5% 2000). Furthermore, lipocalin may promote lipid solubility at
Die ste rs 7.7% the aqueous–lipid inter ace to acilitate the ormation o a thin
Triacylg lyce rid e s 3.7%
Fatty acid s 2.0% layer o lipid on the sur ace o the tear lm.
Fre e ste rols 1.6%
Mucins
MUCIN ‡
MUC1 nd
Mucins are a amily o high-molecular-weight glycoproteins, o
MUC5AC nd which sugars contribute up to 85% o their dry weight. Structur-
MUC4 nd ally, they consist o a polypeptide backbone to which chains o
MUC16 nd sugar molecules attach via O-linkages to the amino acids serine
(Data ad ap te d rom Ti any, 1997.) and threonine. Mucins are a heterogeneous group o molecules
Source s: that can be subdivided into secretory and integrated-membrane
*Main and acce ssory lacrimal g land s. varieties (Cor eld et al., 1997; Hodges and Dartt, 2013). So ar,
†Me ib omian g land s.
‡Ep ithe lial ce lls / g ob le t ce lls.
modern molecular biology techniques have identi ed up to
nd = not d e te rmine d .
20 mucin (MUC) genes, although only our o these (MUC1,
MUC5AC, MUC4 and MUC16) are expressed on the human
ocular sur ace (Gipson and Inatomi, 1997; McKenzie et al., 2000;
Ele ctrolyte s P ug elder et al., 2000; Mantelli and Argüesco, 2008). T e epithelia
Human tears contain approximately the same range o electro- o the cornea and conjunctiva express the transmembrane mucins
lytes as ound in plasma ( i any, 1997). able 2.3 gives typi- MUC1, and to a lesser extent MUC4 and MUC16, which attach
cal values or the ionic composition o human tears. However, to apical microvilli where they orm a hydrophilic base to acilitate
as the electrolyte content o tears varies with ow rate, there is the spreading o the goblet-cell-derived mucin MUC5AC. Mucins
signi cant variation in measured values. During the process play a major role in stabilizing and spreading the tear lm and
o secretion by the lacrimal gland, there is a process o active provide protection against desiccation and microbial invasion
electrolyte transport that is coupled to the passive movement o (Gipson and Inatomi, 1997; Hodges and Dartt, 2013).
water by an osmotic process. Acinar-derived uid is essentially
an isotonic ultra ltrate o plasma. Its composition is altered as Lip id s
it passes along the ductal system, where urther chloride and T e source o lipids in the tear lm is the meibomian glands
potassium ions are secreted. A variety o ion transport proteins embedded within the tarsal plates o each lid. T e blinking pro-
have been identi ed in acinar cells, including sodium–potas- cess is an important mechanism in the expulsion o the secre-
sium A Pase and potassium and chloride channels. tion rom the glands ( i any, 1995). Meibomian lipid (also
known as meibum) is delivered directly as a clear oil onto the lid
Prote ins margins and is spread over the tear lm rom the inner edge o
ear proteins are thought to originate rom three main sources: the lid margins with each blink. T e thickness o the lipid layer
the lacrimal gland, ocular sur ace epithelia and conjuncti- is variable (mean thickness 42 nm, range 15–157 nm; King-
val blood vessels. T e major lacrimal proteins include secre- Smith et al., 2000, 2010), and depending on thickness gives rise
tory IgA, lysozyme, lacto errin and lipocalin ( ormerly known to characteristic inter erence patterns when viewed in specular
as tear-speci c prealbumin) (see able 2.3). IgA, which is re ection (Fig. 2.36) (Guillon, 1998). Meibomian secretion con-
the major immunoglobulin in tears, is secreted as a dimer by sists o a complex mixture o lipids ( able 2.3), including wax
plasma cells in the interstices between lacrimal acini. It then and cholesteryl esters (which together constitute approximately
binds to a receptor on the basolateral aspect o acinar cells, and 70% o meibum), atty acids and atty alcohols ( i any, 1995;
is transcytosed across the cell and secreted into tear uid. IgA Butovich, 2013). T e primary unctions o this secretion are to

Fig . 2.36 Lip id laye r o the p re ocular te ar lm vie we d in sp e cular re -
f e ction. A ‘wave ’ ap p e arance can b e se e n, which re p re se nts the most
commonly ob se rve d lip id p atte rn in the p op ulation.
provide a hydrophobic barrier at the lid margin to prevent over-
spill o tears, and to cover the sur ace o the tear lm to retard
evaporation (Craig and omlinson, 1997).
MO DELS O F TEAR FILM STRUCTURE
T e classical trilaminar model o tear lm structure in terms o
a super cial lipid layer, a middle aqueous layer and deep mucin
layer, rst proposed by Wol and subsequently modi ed by
Holly and Lemp (1977), has received broad acceptance. How-
ever, the results o recent studies have led to a re-evaluation o
the nature o the aqueous and mucinous layers. Several pieces o
evidence have suggested that the mucin contribution to the tear
lm is much greater than was previously thought (Prydal et al.,
1992), and an alternative tear lm model, which possesses a
substantial mucinous phase, has been proposed (Fig. 2.37). T e
nature o the mucinous phase has not been ully established, but
2 Ant e rio r Eye 27
Fig . 2.37 Diag ram showing the comp osition o the p re ocular te ar
lm. Inse ts sho w d e tails o the g lycocalyx and lip id –aq ue ous inte r ace .
(Ad ap te d rom Corf e ld , A. P., Carring ton, S. D., Hicks, S. J. e t al. (1997).
O cular mucins: p urif cation, me tab olism and unctions. Prog . Re tin. Eye
Re s., 16, 627–656.)
is thought to consist o a mixture o soluble and gel- orming
mucins (Hodges and Dartt, 2013).
Co nclusio n
It is clear rom the above account that our understanding o the
structure and unction o the anterior eye is ar rom complete,
which places certain limits on our understanding o clinical,
contact-lens-related phenomena. It is essential, there ore, that
uture research continues to ocus on undamental aspects o
ocular anatomy and physiology, as well as on the more applied
clinical applications that are described in the remainder o this
book.
Acce ss t he co mp le t e re fe re nce s list o nline at
ht t p :/ / www.e xp e rt co nsult .co m.
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King-Smith, P. E., Hinel, E. A., & Nichols, J. J.
(2010). Application o a novel inter erometric
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Another random document with
no related content on Scribd:
administraçion y gouierno deste
mundo inferior para el
cumplimiento de su neçesidad.
Estos no tienen composiçion ni
admistion en sí, ni ay materia que
se rebuelua con ellos estando en
su perfeçion; y ansi te hago saber
que los elementos simples y
puros no los podeis los honbres
vsar, tratar, ni comunicar sino os
los dan con alguna admistion. El
agua sinple y pura no la
podriades beber sino os la
mezclasse naturaleza con otro
elemento para que la podais
palpar y gustar; y ansi se ha de
entender del fuego, ayre y tierra;
que si no estuuiessen mezclados
entre si no los podriamos
comunicar. Pues ansi como el
puro elemento no tiene materia ni
conposiçion en sí, menos la
tienen los çielos, estrellas,
planetas, luna y sol. Tubo
neçesidad el mundo de luz en el
dia, y para esto formó Dios el sol.
Tubo neçesidad de luz en la
noche, y para esto formó luna y
estrellas. Tubo neçesidad de
ayuda para la comun naçençia y
generaçion de las cosas y
conseruaçion y para esto dio Dios
a los planetas, luna y sol y otras
estrellas y çielos virtud que en lo
inferior puedan influir para esta
neçesidad. Y passando por la
region de Eolo, rey de los vientos,
vimos vna gran multitud de almas
colgadas por los cabellos en el
ayre, y atadas las manos atras, y
muchos cueruos, grajos y milanos
que uibas las comian los
coraçones; y entre todas estaua
con muy notable dolor vna que
con gran furia y crueldad la
comian el coraçon y entrañas dos
muy poderosos y hanbrientos
buytres, y pregunté a mi genio
qué gente era aquella. El qual me
respondio que eran los ingratos
que auian cunplido con sus
amigos con el viento de palabras,
pagandoles con engaño y muerte
al tienpo de la neçesidad; y yo le
inportuné me dixesse quién
fuesse aquella desdichada de
alma que con tanto afan padeçia
entre todas las otras, y él me
respondio que era Andronico, hijo
del Rey de Vngria, el qual entre
todos los honbres del mundo fue
más ingrato a la belleza de
Drusila, hija del Rey de
Maçedonia; y yo rogandole
mucho que me dixesse en que
espeçie de ingratitud ofendio, se
sentó por me complazer y ansi
començó. Tu sabras que el Rey
de Albania y Morea hizo gran
exerçito contra el Rey de Lydia
por çierta differençia que entre
ellos auia sobre vnas yslas que
auian juntos conquistado en el
mar Egeo, y por tener el Rey de
Vngria antigua liga y deuida
amistad con el Rey de Albania le
enbió su hijo Andronico con algun
exerçito que le faboreçiesse, que
tenia ya su real asentado en la
Lydia, y vn dia, casi al puesto del
sol, saliendo Andronico del puerto
de Maçedonia en vna galera
ligera para hazer su xornada,
porque ya adelante auia enbiado
al Rey su gente, yendo ya a salir
del puerto casi a mar alta vio que
andaua por el mar vn vergantin
ricamente entoldado con la
cubierta de vn requemado
sembrado[710] de mucha pedreria
que daua gran resplandor a los
que andauan por el mar; y como
Andronico fue auisado del
vergantin mandó a los que yuan
al remo que se açercassen a él, y
yendose más açercando
reconoçieron más su riqueza y yr
damas de alta guisa alli; y asi
Andronico como al vergantin
llegó, por gozar de la presa
mandó afferrar, y luego saltó en él
y con muy gallardo y cortés
semblante se representó ante las
damas, y quando entre ellas vio a
la linda Drusila que en el mundo
no tenia par, que por fama tenia
ya notiçia della, y supo que se era
salida por alli a solazar con sus
damas sin caballero alguno, se le
humilló con gran reuerençia
ofreçiendosele por su prisionero;
y como él era mançebo y gentil
honbre y supo ser hijo del Rey de
Vngria, que por las armas era
cauallero de gran nonbradia, ella
se le rindio[711] quedando
conçertados ambos que acabada
aquella batalla donde yua bolueria
a su seruiçio, y se trataria con su
padre el matrimonio que agora
por palabras y muestra de
voluntad delante de aquellas
damas otorgaron entre sí;
confiando la donzella que su
padre holgaria de lo que ella
huuiese hecho, porque en el
estremo la deseaua conplazer; y
ansi dandose paz con algun
sentimiento de sus coraçones se
apartaron, y siguiendo Andronico
su xornada, ella se boluio a su
ciudad. Luego el dia siguiente
vinieron á Macedonia los mas
valerosos y prinçipales del reyno
de Traçia, enbiados por su Rey,
que estauan en vn confin y
comarcanos, los quales venian a
demandar al Rey de Macedonia
su hija Drusila por muger para el
hijo de su rey y señor; y lo que
suçedió, porque ya creo que
estás cansado de me oyr, y es
venido el dia, en el canto que se
sigue te lo diré. Por agora abre la
tienda y comiença a vender.

Fin de dozeno[712] canto del gallo

de Luçiano.
 NOTAS:
[682] G., contarme.
[683] G., que.
[684] Falta en el ms. R. este titulo.
[685] G., duodeçimo canto.
[686] G. (Tachado): Siguesse el dozeno canto del Gallo de
Luçiano, orador griego, contrahecho en el castellano por el
mesmo autor. (Antes se leia) interprete.
[687] G., incumbrada.
[688] G., enbiado.
[689] G., de vn habito.
[690] Al margen de este parrafo hay en el ms. G., una nota en
letra del siglo xvi, que dice: todo esto es lutheranismo.
[691] R. (Tachado), de azeyte.
[692] R. (Tachado), traeria.
[693] G., quieren.
[694] G., que.
[695] G., humedad.
[696] G., fortissimas.
[697] G., graçiosos.
[698] G., animales.
[699] G., intençion.
[700] G., trapazos de.
[701] G., pareçia.
[702] G., mi amor.
[703] G., a hazer su vaylia.
[704] G., vistieron.
[705] R., que.
[706] G., las que más se fatigan.
[707] G., traen.
[708] G., passemos.
[709] G., desuariar.
 ARGUMENTO
DEL
DEÇIMOTERÇIO
CANTO DEL
GALLO[713]

En el decimoterçio canto que se

sigue el auctor prosiguiendo la
subida del çielo descriue la
pena que se da a los
ingratos[714].

Gallo.—¡O malaventurados
ingratos, aborreçidos de Dios que
es suma gratitud!: ved el pago
que Dios y el mundo os da. Pues
ayer te dezia, Miçilo, cómo Drusila
no auia acabado de dar su fe y
palabra de matrimonio á
Andronico, quando la demandó
Raymundo, hijo del rey de Traçia,
por muger. Pues agora sabras
que ni cobdiçia de más señorio y
reynos, ni de más riquezas, ni de
más poder, la peruertio a que
negasse lo prometido a su
amante. Mas antes de cada dia
penaua más por él y le parecia
auer mucho más herrado y ser
digna de gran pena por auerle
dexado yr; y con esta firmeza y
intinçion respondio á su padre
descubriendole el matrimonio
hecho, al qual no podia faltar, y
como el padre la amaua tanto
despidió los enbajadores diziendo
que al presente no auia
oportunidad para el effecto de su
petiçion; y como el soberuio rey
de Traçia se vio ansi
menospreçiado, por ser el mas
poderoso rey que auia en toda la
Europa y por ser su hijo
Raymundo muy agraçiado
prinçipe y vnico heredero, y de
todas las prinçesas deseado por
marido. Pero por la gran ventaja y
valor de la hermosura de Drusila
la demandó á su padre por
muger, y quanto más se la
negaron más él se afiçionó a ella,
y ansi propuso con gran yra de la
conquistar por armas, de tal
suerte que quando ella no
pudiesse ser vençida a lo menos
perdiesse el reyno y neçesitarla
hazerlo por fuerça, avnque no con
intinçion de afrontar ni injuriar su
valerosa persona; y ansi luego se
lançó en el reyno de Maçedonia
con grande exerçito quemando,
talando y destruyendo todo el
estado; y la desdichada Drusila
quando vió á su padre y
hermanos con tanta afliçion,
llorando maldezia su triste hado
que á tal estado la auia traydo, y
no sabia con qué más cunplir con
ellos que con rogarles la
quitassen la vida, pues ella era la
ocasion y causa de aquella
tenpestad, y por muchas vezes se
determinó a se la quitar ella a sí
mesma, sino que temia el estado
miserable de la desesperaçion, y
hazer pessar a su querido y
amado Andronico, porque creya
çierto[715] dél que la amaua; y
ansi suçedió que en vna batalla
campal que les dio Raymundo,
por la gran pujança de esfuerço y
exerçito los vençió y mató al rey
de Maçedonia y dos hijos suyos.
De lo qual la desdichada Drusila
se sintió muy afligida y le fue
forçado huyr del enemigo y su
furia y recogerse en vn castillo
que era en el fin de su reyno en
los confines de Albania, que no
tenia ya más que perder; y alli
muy cubierta de luto y miseria
esperaua lo que della Raymundo
quisiesse hazer, teniendo por
mejor y más façil perder su vida,
pues ya la estimaua por muerte,
antes que perder al su Andronico
la fe; y estando ansi
desconsolada, huerfana y sola sin
algun socorro, vino nueua al
reyno de Albania cómo[716] el rey
de Lydia hauia vençido en batalla
a su rey y tenía preso a
Andronico, hijo del rey de Vngria;
y como Drusila tenia toda su
esperança en el fin de aquella
batalla, pensando que como della
saliesse vitorioso el rey de
Albania vernia con Andronico en
su fabor y que anbos bastarian
para la restituir en su reyno, como
ya se vió la misera sin alguna
esperança de remedio no hazia
sino llorar congojandose[717]
amargamente, maldiziendo su
suerte desdichada, no sabiendo a
quién se acorrer. No tuvo la
cuytada otra cosa de qué asir
para el entretenimiento de su
consolaçion sino considerar la
causa tan bastante que tenia
porque llorar, que le seria ocasion
de morir, y ansi de acabar su
dolor; y como Raymundo la
importunaba acortandola de cada
dia mas los terminos de su
determinaçion, ya como muger
aborrida, teniendo por çierto que
ningun suçeso podria venir que
peor fuesse que venir en manos
de Raymundo siendo vibo su
Andronico, determinó yr por el
mundo a vuscar alguna manera
como le libertar o morir en prision
con él; y ansi se vistio de los
vestidos de vno de sus hermanos,
y cortandose los cabellos
redondos al uso de los varones
de la tierra se armó del arnes y
sobre veste de su hermano sin
ser sentida, ni comunicandolo con
alguna persona, y un dia antes
que amaneçiesse se salió del
castillo sin ser sentida de las
guardas de fuera, porque a las de
dentro ella las ocupó aquella
noche como no la pudiessen
sentir; y ansi con la mayor furia
que pudo caminó para el puerto,
donde halló vna galera ligera que
estaua de partida para la Lydia,
en la qual se fletó pagando el
conueniente salario al piloto, y
con mucha bonança y buen
tenporal hizo su viaje hasta llegar
al puerto de su deseado fin.
Consolauasse la desdichada en
hollar la tierra que tenia en prision
todo su bien, y quando llegó a la
gran çiudad donde residia el rey
teniasse por muy contenta
quando via aquellas torres altas
en que pensaua estar secrestado
su amor, y ansi a la más alta y
más fuerte le dezia: ¡O la más
bienauenturada estançia que en
la tierra ay! ¿Quién te hizo tan
dichosa que mereciesses ser
caxa y buxeta en que estuuiesse
guardado el precioso joyel que
adorna y conserua mi coraçon?
¿Quién te hizo bote en que
ençerrasse conserua tan cordial?
¡O si los hados me conuertiessen
agora en piedra de tan feliz
edefiçio, porque a mi contento
gozasse de mi desseado bien! Y
diziendo estas y semejantes
lastimas, llorando de sus ojos se
entró en la çiudad y fuesse
derecha al palaçio y casa del rey,
y apeada de su cauallo se entró al
retraimiento[718] real, y puesta de
rodillas ante el rey le habló ansi.
Muy alto y muy poderoso señor, a
la vuestra alteza plega saber
cómo yo soy hijo del rey de
Polonia; y deseo de exerçitarme
en las armas para mereçer ser
colocado en la nonbradia de
cauallero me ha hecho salir de mi
tierra, y teniendo notiçia que tan
auentajadamente se platican las
armas en vuestra corte soy
venido a os seruir. De manera
que si mis obras fueren de
cauallero, ofreçida la oportunidad
terneme por dichoso tomar la
orden de caualleria de tan
valeloso principe como vos; y si
en vuestro seruiçio me reçebis me
hareis, señor, muy gran merçed.
Estauan delante la reyna y su hija
Sophrosina que era dama de gran
veldad, y el hijo del rey; y como
vieron a Drusila tan hermoso y
apuesto donzel á todos contentó
en estremo, y les plazió su
ofrecimiento, y a Sophronisa (sic)
mucho más; y despues que el rey
su padre le agradeçió su venida y
buena voluntad, le ofreçió todo
aquel aprouechamiento que en su
casa y reyno se le pudiesse dar.
Sophrosina le demandó a su
padre por su donzel y cauallero, y
su padre se le dió: y Drusila le fue
a bessar las manos por tan gran
merced: Sophrosina estaua muy
hufana de tener en su seruiçio vn
tan apuesto y hermoso donzel,
porque çiertamente ansi como en
su habito natural de muger era la
mas hermosa donzella que auia
en el mundo, y con su veldad no
auia cauallero que la viesse que
no la deseasse. Ansi por la
mesma manera en el habito de
varon tenia aquella ventaja que
toda lengua puede encareçer, en
tanta manera que no auia dueña
ni donzella que no deseasse
gozar de su amor; y ansi
Sophrosina dezia muchas veces
entre sí que si fuesse a ella çierto
que el su donzel era hijo del rey
de Polonia, como él lo auia dicho,
que se ternia por muy contenta
casar con él: tan contenta estaua
de su postura y veldad; y ansi en
ninguna cosa podia Sophrosina
agradar á Drusila que no lo
hiziesse de coraçon. Y un día
hablando delante de algunos
caualleros y reyna su madre, de
la batalla y de la muerte del rey
de Albania, vinieron á hablar de la
prision de Andronico hijo del rey
de Vngria, y la reyna dixo que
çiertamente seria justiçiado muy
presto, porque mató en la batalla
vn sobrino suyo hijo de su
hermana, y que su madre no se
podia consolar por la muerte de
su hijo sino con auer Andronico
de morir, y que para esto tenia ya
la palabra del rey; y como Drusila
esto oyó pensó perder la vida de
pessar, y con mucha disimulaçion
se puso a pensar cómo podria
libertar a su amante avnque ella
muriesse por él; y ansi como
Sophrosina se recogió a su
aposento pusosse Drusila de
rodillas ante ella suplicando la
hiziese vna merçed, haziendole
saber en cómo ella auia
conçebido gran piedad de
Andronico, por çertificarle la reyna
su señora que auia de morir. Que
le suplicaua le diesse liçencia
para le visitar y consolar porque
en ninguna manera se podria
sufrir a estar presente en la
çiudad a le ver morir. Sophrosina
como entendió esto haria a
Drusila gran plazer le dió luego vn
anillo muy preçiado que ella traya
en su dedo y le dixo que se
fuesse con él al alcayde del
castillo y le dixesse que se le
dexasse ver y hablar. No te puedo
encareçer el goço que Drusila con
el anillo lleuó, y como llego al
castillo y le mostró al alcayde y
reconoçió el anillo muy preçiado
de su señora Sophrosina: y por lo
que conoçia de los fabores que
daua al su donzel, luego le hizo
franco el castillo y le dió las
llaues, y sin mas conpañia ni
guarda le dixo que entrasse en la
torre de la prision. Como
Andronico sintió abrir las puertas
temiose si era llegada la hora en
que le auian de justiçiar, porque le
pareçió desusada aquella visita, y
estaua confusso pensando qué
podia ser; y avnque no tenia mas
prisiones que la fuerça de aquella
torre afligiale mucho la soledad y
el pensar la hora en que auia de
morir; y como Drusila entró en la
prision y reconoçío al su amado
Andronico, avnque flaco y
demudado todo, se le fue a
abrazar y bessar en la boca, que
no se podia contener; y como
Andronico se sintio ansi acariçiar
de vn mançebo en vn estado tan
miserable como aquel, estaba
confusso y turbado, sospechoso
que le llorauan el punto de su
muerte; y cuando ya su Drusila se
le dió á conoçer y boluió en sí no
ay lengua que pueda contar el
plazer que tuuieron anbos a[719]
dos. Luego le contó por estenso
cómo auia venido alli, y cómo
perdió sus padres, hermanos y
reyno, y el estado en que estaua
en el fabor de su señora
Sophrosina, y la confiança y
credito que se le daua en todo el
reyno[720], y cómo sabia
çiertamente que auia de morir y
muy breue, sin poderlo ella
remediar por ser muger; y que por
tanto conuenia que luego
tomando los habitos que ella
traya, que se los dio Sophrosina,
la dexasse con los que él tenia
vestidos en la prision, y que él se
fuesse a vuscar cómo la libertar.
En fin, pareçiendo bien a anbos
aquel consejo y siendo auisado
por Drusila de muchas cosas que
conuenia hazer antes que
saliesse de la çiudad: cómo se
auia de despedir de Sophrosina, y
cómo auia de auer su arnes,
vestiendose las ropas que ella
lleuaua, y tomando el anillo, y
çerrando las puertas de la torre se
salió, y dadas las llaues al
alcayde con mucha disimulaçion
se fue al palaçio sin que alguno le
echasse de ver por ser ya casi a
la noche, y entrando a la gran
sala halló a Sophrosina con sus
padres y corte de caualleros en
gran conuersaçion; y puesto de
rodillas ante ella le dio el anillo; y
por no dar Sophrosina cuenta al
rey ni reyna de ninguna cosa no
le habló en ello mas, pensando
que estando solos sabria lo que
con Andronico passó; y Andronico
sin mas detenimiento se fue al
aposento de Drusila conforme al
auiso que le dio, y vestido su
arnes y subiendo en su cauallo se
salio la puerta de la çiudad.
Esperó Sophrosina aquella noche
si pareçia ante ella el su donzel, y
como no le vio, venida la mañana
le enbió a vuscar, y como le
dixeron que la noche antes se
auia ausentado de la çiudad
penso auerlo hecho por piedad
que tubo de Andronico por no le
ver morir; y ansi trabajaua
Sophrosina porque se executasse
la muerte en Andronico
esperando[721] que luego bolueria
su donzel sabiendo[722] auerse
hecho justicia dél; y ansi se sufrió,
y respondia al rey y reyna quando
preguntauan por el, diziendo que
ella le enbió vna xornada de alli
con vn recado. Andronico con la
mayor priesa que pudo
caminando toda la noche se fue
para el rey de[723] Armenia,
porque supo que tenia gran
enemistad con el rey de Lydia, y
le dixo ser vn cauallero de Traçia,
que auia recebido vn gran agrauio
del rey de Lydia: que le suplicaua
le diesse su exerçito, y que él le
queria hacer su capitan general;
que él le prometia darle
façilmente el reyno de Lydia en su
poder, y que solo queria en pago
le hiziesse merced del[724]
despojo del palacio real y
prisioneros del castillo; y ansi
conçertados caminó Andronico
para Lydia con el rey de Armenia
y su exerçito, y salido el rey de
Lydia al campo con su exerçito le
mató Andronico en la[725] batalla
y le desuarató y[726] entró la
ciudad, y tomó en su guarda el
palaçio del rey, y se fue al castillo
y abierta la prision sacó de alli a
su Drusila con gran alegria y
plazer de anbos y gran gozo de
bessos y abrazos; y descubriendo
su estado y ventura a quantos lo
querian saber[727], vistio a Drusila
de habitos de dama, que
admiraua a todos su hermosura y
velleza; y poniendo en poder del
rey de Armenia á la reyna[728] y
todo el reyno de Lydia, y diziendo
que queria á Sophrosina para
darsela por muger a vn hermano
suyo la enbarcó juntamente con
todo el tesoro del rey. No huuieron
salido dos leguas del puerto
quando se les leuanta el mar con
tempestad muy furiosa; que[729]
despues de dos dias aportaron a
vna ysla sola y desierta y sin
habitaçion que estaua en los
confines de Rodas[730]; yua
Sophrosina muy miserable y
cuytada llena de luto, y Andronico
se la yua consolando, y como era
donzella y linda que no auia
cunplido catorce años bastó entre
aquellos regalos y lagrimas mouer
el coraçon de Andronico con su
hermosura y belleza; y ansi como
enhastiado de la su Drusila passó
todo su amor en Sophrosina: que
ya si a Drusila hablaua
comunicaua era con simulaçion,
pero no por voluntad; y ansi
fingiendo regalar á Sophrosina de
piedad, disimulaua su maliçia
encubierta, porque so color de
que la lleuaua para su hermano la
acariçiaua para si, pareçiendole
no ser aquella joya para
desechar, y ansi ardiendo su
coraçon con la llama que
Sophrosina le causaua, sospiraua
y lloraua disimulando su pena.
Pues llegados al puerto de la ysla,
como Drusila llegó cansada de las
malas noches y dias
passados[731] saltó luego en tierra
ya casi a la noche, y auiendo
çenado no queriendo Sophrosina
salir del nauio por su desgracia,
sacaron[732] al prado verde vn
rico pauellon con vna cama:
el[733] qual reçibió aquella noche
los desiguales coraçones[734] de
Andronico y Drusila en vno; y
como la engañada Drusila con el
cansancio se adormió, y el infiel
de Andronico la sintio dormida,
poco a poco sin que le sintiesse
se leuantó de la cama[735] junto á
la media noche y tomandola todos
sus vestidos la dexó sola y
desnuda en el lecho y se lançó en
el nauio; y ansi mandó a su gente
y marineros[736] que sin más
detenimiento leuantassen vela y
partiessen de alli, y con tienpo de
bonança y prospero viento
vinieron en breue a tomar puerto
en el reyno de Maçedonia,
algunas villas que avn estauan
por Drusila, porque Raymundo
era ydo a conquistar a Siçilia. La
desdichada de Drusila como de
su sueño despertó començó a
vuscar por la cama su amante,
estendiendo por la vna parte las
piernas, y por la otra echaua[737]
los brazos; y como no le halló,
como furiosa y fuera de seso saltó
del lecho desnuda en carnes y sin
sosiego alguno se fue a la ribera
adonde estaua[738] el nauio, y
como no le vio, presumiendo avn
dormir y ser sueño aquello que
via[739] se començó cruelmente a
herir por despertar; y ansi
arañando[740] su hermoso rostro
que el sol obscureçía con su
resplandor y mesando sus
dorados cabellos corria a vna
parte y a otra por la ribera como
adiuinando su mala fortuna. Daua
grandes bozes llamando su
Andronico; pero no ay quien la