Table Of ContentScientific Foundations
of
Ophthalmology
Edited by
EDWARD S. PERKINS
PhD(Lond), MD, MB, BS, FRCS(Eng),
LRCP(Lond), DOMS(Eng)
Professor of Experimental Ophthalmology,
Institute of Ophthalmology, University of London;
Honorary Consultant Ophthalmologist, Moorfields Eye Hospital
and
DAVID W. HILL
MB, BS(Lond), FRCS(Eng), DO(Eng)
Research Professor of Ophthalmology,
Royal College of Surgeons of England;
Consultant Ophthalmologist, Moorfields Eye Hospital
LONDON
WILLIAM HEINEMANN MEDICAL BOOKS LTD
First published 1977
© E. S. Perkins and D. W. Hill, 1977
ISBN 0 433 25015 1
Text set in Monotype Times New Roman and printed in
Great Britain by Cox and Wyman Ltd.,
London, Fakenham and Reading
LIST OF CONTRIBUTORS
DOUGLAS R. ANDERSON, MD Professor of Emergency Medicine; Co-Director of
Associate Professor, Department of Ophthalmology Retinal Vascular Service, Wilmer Ophthalmological
(Bascom Palmer Eye Institute), University of Miami Institute, Johns Hopkins University and Hospital,
School of Medicine, Miami, Florida Baltimore, Maryland
SAMUEL B. ARONSON, MD WALLACE S. FOULDS, MD, ChM, FRCS
President, Eyetis Foundation, San Francisco, California Tennent Professor of Ophthalmology, University of
M. A. BEDFORD, FRCS Glasgow ; Honorary Consultant Ophthalmologist,
Consultant Eye Surgeon, St. Bartholomew's Hospital, Greater Glasgow Health Board
London; Consultant Surgeon, Oncology Unit, Moorfields BRIAN HARCOURT, MA, MB, FRCS
Eye Hospital, London Consultant Ophthalmic Surgeon, Leeds General In
ISAAC BEN SIRA, MD firmary; Clinical Lecturer in Paediatric Ophthalmology,
Associate Professor of Ophthalmology, Tel-Aviv Uni
University of Leeds
versity Medical School, Tel-Aviv, Israel; Chairman,
RUTH VAN HEYNINGEN, MA, DPhil, DSc
Department of Ophthalmology, Beilinson Medical
Senior Research Officer, University of Oxford
Center, Petah Tiqva, Israel
A. L. HOLDEN, MA, DPhil
ALAN C. BIRD, MD, FRCS
Senior Lecturer, Institute of Ophthalmology, University
Reader in Clinical Ophthalmology, Institute of Ophthal
of London ; sometime Fellow of Magdalen College and
mology, University of London
New College, Oxford
R. K. BLACH, MA, MD, FRCS
K. JESSEN, Dipi Phys
Consultant Ophthalmologist, Moorfields Eye Hospital,
Physikalisch-Technisches Bundesanstalt, Institut Berlin
London; Honorary Consultant Ophthalmologist, Ham
BARRIE R. JONES, BSc, MB, ChB, MRCP, FRCS
mersmith Hospital, London
Professor and Director, Department of Clinical Ophthal
JOHAN BOURS, PhD
mology, University of London, and Moorfields Eye
Biochemist, Division of Biochemistry of the Eye, Clinical
Hospital, London; Director, World Health Organization
Institute of Experimental Ophthalmology, University of
Collaborating Centre for Reference and Research on
Bonn
Trachoma and other Chlamydial Infections
DERRICK A. BREWERTON, MD, FRCP
Consultant Physician, Rheumatology Department, HERBERT E. KAUFMAN, MD
Professor of Ophthalmology; Chairperson, Department
Westminster Hospital, London
of Ophthalmology; Professor of Pharmacology, Uni
NICHOLAS A. P. BROWN, MB, BChir, FRCS
versity of Florida, Gainesville, Florida
Formerly Senior Lecturer, Institute of Ophthalmology,
London J. KELSEY, FRCS
PROFESSOR SIR CYRIL A. CLARKE, KBE, MD, FRCP, FRS Consultant, Electrodiagnostic Clinic, Moorfields Eye
Nuffield Research Fellow, Department of Genetics, Hospital, London
University of Liverpool ; Emeritus Professor of Medicine, COLIN M. KEMP, BSC, PhD
University of Liverpool Senior Lecturer, Institute of Ophthalmology, University
A. J. COAKLEY, MD, MRCP of London
Medical Registrar, St. Thomas' Hospital, London G. A. S. LLOYD, MA, DM, FFR, DMRD
DESMOND N. CROFT, MA, DM, FRCP Consultant Radiologist, Moorfields Eye Hospital,
Consultant Physician, St. Thomas' Hospital, London London
A. F. DEUTMAN, MD JOHN MARSHALL, BSc, PhD
Professor of Ophthalmology, Institute of Ophthalmology, Senior Lecturer, Department of Visual Science, Institute
University of Nijmegen, Nijmegen, The Netherlands of Ophthalmology, University of London
J. A. DRAEGER, MD ROBERTA L. MEYERS, PhD
Professor of Ophthalmology ; Head of Eye Department, Associate Professor of Ophthalmology, Jules Stein Eye
Bremen, Germany Institute, UCLA School of Medicine, Los Angeles,
W. ERNST, MA, PhD California
Lecturer, Institute of Ophthalmology, London ISAAC C. MICHAELSON, FRCP, DOMS, PhD
PETER FELLS, MA, MB, FRCS Friedenwald Professor of Research in Ophthalmology;
Consultant Ophthalmologist, Moorfields Eye Hospital; Director, Jerusalem Institute for the Prevention of
Senior Lecturer, Institute of Ophthalmology, University Blindness, Hebrew University, Hadassah Medical School,
of London Jerusalem, Israel
STUART L. FINE, MD STEPHEN J. H. MILLER, MD, FRCS
Assistant Professor of Ophthalmology; Assistant Consultant Surgeon, Moorfields Eye Hospital, London
X LIST OF CONTRIBUTORS
BRANKO NIZETIC, MD, DOph (Parma), MPH (UC KIRSTI H. TAKKI, MD
Berkeley) Department of Ophthalmology, Kivelä City Hospital,
Reader in Ophthalmology, University of Rome; Helsinki
Regional Officer for Public Health Ophthalmology, DAVID TAYLOR, MRCP, FRCS
World Health Organization. Copenhagen Consultant Ophthalmologist, Hospital for Sick Children,
D. A. PALMER, DSC, PhD, DIC Great Ormond Street, and National Hospital for
Senior Lecturer, Institute of Ophthalmology, University Nervous Diseases, Queen Square, London
of London RAMESH C. TRIPATHI, MD, MS, PhD, DO, MRC Path
J. C. PASHLEY, BSC, MIEEC Professor of Ophthalmology, University of Chicago
Department of Experimental Ophthalmology, Institute MARCOS TSACOPOULOS, MD
of Ophthalmology, University of London Chargé de Recherche, Medical School, University of
ARNALL PATZ, MD Geneva
Professor of Ophthalmology, The Seeing Eye Research G. VENKATASWAMY, MS, FAMS
Professor, Director of Retinal Vascular Service, Wilmer Professor of Ophthalmology, Medical College, Madurai,
Ophthalmological Institute, Johns Hopkins University India
and Hospital, Baltimore, Maryland J. O. Williams, MB, MRCP
A. R. PETTIGREW, BSC, MSC Senior Medical Registrar, St. Thomas' Hospital, London
Biochemistry Department, Queen Mother's Hospital, A. F. WINDER, MA (Oxon), BM, BCh, PhD, BSc (Lond)
Royal Hospital for Sick Children, Glasgow Senior Lecturer in Chemical Pathology, Institute of
AMJAD, H. S. RAHI, BSC, MD, PhD Ophthalmology, University of London; Honorary
Senior Lecturer in Pathology, Institute of Ophthal Consultant in Chemical Pathology, Moorfields Eye
mology, University of London; Honorary Consultant Hospital, London
Pathologist, Moorfields Eye Hospital J. C. WOODROW, MD, FRCP
EMANUEL ROSEN, BSc, MD, FRCS, FRPS Reader in Medicine, University of Liverpool
University Department of Ophthalmology, Manchester K. C. WYBAR, BSC, MD, ChM, FRCS
Royal Eye Hospital Ophthalmic Surgeon, The Hospital for Sick Children,
M. D. SANDERS, FRCS Great Ormond Street, and the Royal Marsden Hospital;
Consultant Ophthalmic Surgeon, National Hospital for Surgeon, Moorfields Eye Hospital; Lecturer in Ophthal
Nervous Diseases, Queen Square, London mology, Institute of Ophthalmology, University of
EMIL S. SHERRARD, BSC, PhD London; Civilian Consultant in Ophthalmology, the
Senior Lecturer, Institute of Ophthalmology, University Royal Navy
of London YUVAL YASSUR, MD
VERNON H. SMITH, MA, MB, BChir, FRCS Lecturer in Ophthalmology, Hebrew University, Jerusa
Consultant Surgeon, Birmingham and Midland Eye Hos lem, Israel; Vice-Chairman, Department of Ophthal
pital; Senior Clinical Tutor, University of Birmingham mology, Beilinson Medical Center, Petah Tiqva, Israel
PREFACE
In this volume are collected essays on a variety of laboratory, clinical and
community health topics, each from an author active in his particular field.
In conformity with other volumes in this series we invited each author to
present his view of a particular subject, a personal contribution focusing
attention on current thinking in the field. Some of our contributors are
laboratory scientists, others clinicians; together they have brought a
variety of scientific disciplines to bear on the problems of the eye.
The first part of the book considers the eye as a vegetative organ, cover
ing topics in anatomy, sociology and genetics, and some aspects of
pathology which are of particular importance at the present time in
determining our approach to clinical problems. A section on the epi
demiology of blindness and blinding diseases will we hope stimulate
interest in the public health aspect of ophthalmology. The second part of
the book considers vision, its basic physiology, and binocular vision in
health and disease. The final part is clinical, devoted to two subjects,
modern techniques of investigation and the guiding principles in some
newer areas of treatment.
Inevitably the spirit of this book is eclectic; were we to start again the
choice of essays might be different, yet equally valid. It is not intended to
supplant the formal texts and detailed monographs, but to provide a way
into many areas of advancing knowledge: to enable the reader, post
graduate student, practising ophthalmologist, or worker in another
discipline, to orientate himself before plunging into the literature.
We wish to thank our contributors and ask their forbearance, where, in
some fields, new ideas have overtaken their contributions: some minor
revisions of the text have been incorporated during production. It is with
regret that we record the untimely death of Miss M. Welch, but wish
to express our appreciation of her tireless and experienced assistance in
preparing the manuscripts for publication.
August, 1977 E.S.P.
D.W.H.
XI
SERIES EDITOR'S FOREWORD
It is not as an ophthalmologist (which I am not) that Messrs. Heinemann
Medical have invited me to contribute this foreword. I was invited as
overall editor of the Scientific Foundations series that was launched in
1967, after and through the publication of the Scientific Foundations of
Surgery*
The ensuing decade has seen the publication, or the preparation, of a
library of some dozen more or less similar works devoted to the background
knowledge of as many different clinical disciplines. Of these, ophthal
mology is the latest.
The ideas that inspired the original volume were, firstly, to present
through selected authors human physiology applicable to surgery, for the
benefit of senior students; secondly to attempt to influence basic teaching
and examining towards a more vocational approach, and, finally, to offer
to clinical teachers as well as to students, a readily available text for the
revision and up-dating of their basic science knowledge, and, in particular,
that of human physiology and of the physiological variations induced by
various forms of treatment and by surgical procedures.
The editors of this present book are to be congratulated on following
most closely the pattern of our original production. The bibliographies are
commendably selective and correspondingly of reasonable length. The
illustrations are abundant and helpful.
It is no part of my assignment to review this book and I am making no
attempt to do so. However, as a past examiner in the Royal Colleges, I do
know that Fellowship candidates in ophthalmology have been particularly
hard pressed. The abundant information available between the covers of
this book should go some considerable way towards easing their burdens.
Charles Wells, CBE, SPk, FRCS, Hon LID, Hon FACS,
Professor Emeritus of Surgery, University of Liverpool
* Scientific Foundations of Surgery, Second edition 1974. Eds. Wells, Charles; Kyle, James
(Aberdeen) and Dunphy, Englebert (University of California). London: Heinemann Medical.
FOREWORD
This is a good, indeed an excellent book, a very worthy ninth volume of
the Heinemann Medical series. The editors, E. S. Perkins and D. W. Hill,
have chosen a team of 51 contributors from Britain and the rest of Europe,
America and Asia, each of them an authority on his subject and every one
of them able to write clearly and interestingly. Its 11 sections cover the
entire groundwork of the basic aspects of ophthalmology—anatomy,
physiology, genetics, immunology, metabolic disease, epidemiology, the
effects of light on the ocular pigments, and electrophysiology, psycho-
physiology, binocular vision, and diagnostic techniques—each with a useful
list of important references to the literature. There need be no hesitation
in recommending it warmly to ophthalmologists and neurologists who are
interested in such subjects. It undoubtedly fills a much felt want.
Sir Stewart Duke-Elder, GCVO, FRS
Xlll
1. THE AQUEOUS OUTFLOW PATHWAY IN VERTEBRATE EYES
RAMESH C. TRIPATHI
Introduction body and the iris root; hence the distinction of corneo-
Despite wide variations in the mode of life and the habitat scleral trabeculae, uveal trabeculae and iris processes
of vertebrates (whether terrestrial, arboreal, amphibious (pectinate fibres) respectively.
or aquatic), the close similarity in the ontogeny and basic The corneoscleral and outer uveal trabeculae are
features of their eyes is most remarkable. In all species, the flattened, perforated sheets, orientated circumferentially,
cavity of the anterior chamber acts as a reservoir for a clear parallel to the surface of the limbus. The inner one or two
watery fluid, the aqueous humour, which through its layers of uveal sheets are, however, cord-like, and are
hydrodynamics is responsible for maintaining the normal orientated predominantly in a radial net-like fashion,
intraocular pressure, and this, in conjunction with the enclosing large oval, circular or rhomboidal spaces. The
fibrous tunics of the eyes, provides the stability of ocular thicker, radially orientated iris processes, reminiscent of
dimensions for the performance of visual function. There is the pectinate ligaments seen in lower mammals, are widely
considerable evidence that in most vertebrates the aqueous
humour is continuously formed in the posterior chamber,
largely as a secretory product from the cells of the ciliary
epithelium.
The comparative morphology and physiology of the
pathways responsible for continuous drainage of the
aqueous humour in vertebrate eyes may be discussed under
two main headings :
The 'conventional' drainage pathway is responsible for the
bulk drainage of the aqueous humour from the angle of the
anterior chamber into the channels located in the limbal
region of the eye. An obstruction in this pathway leads to
raised intraocular pressure and the clinical condition of
glaucoma.
The accessory drainage routes include uveoscleral
drainage, diffusion along the iris vessels, posterior drainage
(through the vitreous into the retina and optic nerve) and
transcorneal flux. Available evidence suggests that these
routes do not contribute significantly to the bulk outflow of
aqueous and this chapter will be concerned only with the FIG. 1. Photomicrograph of ciliary and limbal regions of human eye in
meridional section. Note clearly defined angle of the anterior chamber
conventional drainage pathway. (AC), compact ciliary muscle (CM), ciliary epithelium, (CE). The
As most information available relates to the eyes of aqueous drainage pathway consists of trabecular meshwork (TM),
Schlemm's canal (SC) and intrascleral collector channels (IS). ( x 54.)
mammals, and in particular those of primates, it is appro
priate to discuss it in descending order of evolution.
spaced. Although there are variations in the thickness of
Primates the trabeculae and in the proportion of the connective
In primate eyes, the conventional drainage pathway, tissue components, histologically they are made up of
entirely confined to the limbal region, consists of the collagen fibres together with elastic tissue, and a zone of
trabecular meshwork, the canal of Schlemm, and the basal-lamina material covered by a layer of flattened
intra- and episcleral system of collector channels, including endothelial cells.
the aqueous veins. The angle of the anterior chamber is The trabecular meshwork forms a labyrinth of extra
clearly defined, probably as a consequence of evolution and cellular intercommunicating spaces of variable size and
the massive development of the ciliary body, which forms a shape. In the normal eye, the ease of flow of aqueous
compact triangular structure (Fig. 1). humour through these spaces is indicated by the fact that
The trabecular meshwork, located in the inner limbus, dyes, colloidal suspensions and particulate matter of
spans the angle as a wedge-shaped band with the apex certain sizes can be readily traced when introduced into the
inserted into the peripheral termination of Descemet's anterior chamber. From the trabecular meshwork, the
membrane and the deeper corneal lamellae, and the base aqueous humour passes into the canal of Schlemm, a
connected to the scierai spur, the anterior face of the ciliary circumferential vessel, elliptical in shape and located
2 SCIENTIFIC FOUNDATIONS OF OPHTHALMOLOGY
between the compact corneosclera and the trabecular 'closed' systems respectively). These apparently opposing
meshwork. Its trabecular wall is composed of a zone of concepts probably originated a century ago. The sup
cell-rich supporting tissue or endothelial meshwork of porters of the 'open' system concept believed that there
variable thickness which intervenes between the outermost were direct communications across the endothelial lining of
corneoscleral trabecular sheet and the endothelial lining of Schlemm's canal of a size discernible by light microscopy.
the canal (Fig. 2). The extracellular spaces in this region Consequently, the possibility of the openings being tubules
lined by endothelium, intercellular gaps or some undefined
pores was considered. Histological studies with and
without injection experiments, however, failed to clarify
the size and the nature of the openings. The advocates of
the closed system concept, on the other hand, have insisted
that the endothelial lining of Schlemm's canal is a con
tinuous membrane and that the drainage of aqueous
humour must therefore depend upon seepage, some form
of passive filtration or even an active transport mechanism.
To resolve these apparent contradictions and with the
advent of electron microscopy, a number of ultrastructural
studies have been undertaken to clarify the functional
morphology of the exit pathway of the aqueous.
Ultrastructural studies of the endothelial lining of the
canal of Schlemm have now clearly shown it to be charac
terized by a single layer of cells resting on a tenuous and
interrupted basal lamina (Fig. 2). Adjacent cells are joined
by poorly defined 'tight' junctions which occupy only a
small area of the cell surface. Schlemm's canal shows many
tortuous blind channels or diverticula lined by endothelium
FIG. 2. Survey electron micrograph of the trabecular wall of Schlemm's
canal (SC) of normal human eye in meridional section. The endothelial and extending for a variable distance into the meshwork.
lining (N, cell nuclei) is characterized by a single layered membrane, Scanning electron microscopy of the endothelial lining
many cells of which contain giant vacuoles (V). OS, open extracellular
spaces of the supporting tissue zone or endothelial meshwork. ( x 4375. of the trabecular wall of Schlemm's canal clearly reveals the
- v**2
Ws^
i^gl^Sk *
FIG. 3. Scanning electron micrograph of the endothelial lining of the trabecular wall of Schlemm's canal viewed from the luminal aspect. Note the spindle-
shaped appearance of the cells, their long axes being parallel to the canal circumference. The central bulges correspond to the location of cell nuclei and
giant vacuoles. The asterisk denotes a collapsed vacuole. ( x 2000.)
appear to be narrower than in the remainder of the individual cells to be generally spindle-shaped with a
trabecular meshwork, and it is thought that this region may central bulge and tapering rounded ends (Fig. 3). The long
account for some resistance to aqueous outflow. axis of each cell is usually orientated parallel to the cir
The structure and function of the canal of Schlemm has cumference of the canal. The cells measure some 40-100
been the subject of much debate amongst morphologists, μπι in length and 5-12 μπι in width, centrally. Ultrathin
physiologists and clinicians, especially as to whether or not sections of the cells examined by transmission electron
the outflow of aqueous humour across the trabecular wall microscopy show them to contain the usual intracellular
of Schlemm's canal takes place via pores (the 'open' and organelles: a centrally located oblong nucleus responsible
THE AQUEOUS OUTFLOW PATHWAY IN VERTEBRATE EYES 3
for an apical bulge in the cell, a moderate number of The filling of the vacuoles with colloidal ferritin serum
mitochondria, smooth- and rough-surface endoplasmic solution, and its passage through a vacuolar transcellular
reticulum, Golgi apparatus, membrane-bound dense bodies, channel into the lumen of the canal, is seen in Fig. 5. In
multivesicular bodies, centrioles, glycogen and free ribo- our experimental studies, however, no leakage through the
nucleic acid granules. The cells are rich in fine cytoplasmic intercellular route was seen. Although consideration must
filaments, orientated along their long axis. be given to the possible role of micropinocytotic vesicles
A specialized feature of many lining endothelial cells is in the transfer of fluid, their contribution to the bulk
the presence of giant vacuoles (Fig. 2), which over the past drainage of aqueous humour would seem to be small,
decade has aroused wide interest. The possibility that they since during the experiment (approximately thirty minutes)
were artefacts has also been considered by many workers, tracer particles of colloidal dimensions were only rarely
but it is now established that the vacuoles are a real seen in these caveolae. In any case, this mode of transport
morphological entity, and not a product of pathological or cannot account for the rapidity and size of the tracer
post-mortem change, since they are found in fresh ante- elements which leave the anterior chamber and can be
mortem tissue and also following in situ fixation by a recovered from the exit channels. In the absence of any
•-se \it
FIG. 4. Electron micrograph of the endothelial lining of Schlemm's canal FIG. 5. Selected electron micrographs of serial sections of a vacuolar
(SC) showing filling of giant vacuoles (V) following intracameral injec transcellular channel with an erythrocyte in transit, (a) Part of the
tion of ferritin serum solution. Note the passage of the tracer into the erythrocyte (E) projects into the vacuole through its basal opening
canal through a vacuolar transcellular channel (arrows denoting basal (arrow) ; (b) protrusion of a membraneous structure (probably a ghost
(bottom) and apical (luminal) openings). The intracellulai junctions erythrocyte) is seen through the apical opening of the vacuole (arrow).
(Z) are intact, (x 16 250.) SC, Schlemm's canal, (x 10 000.)
variety of reliable techniques. Electron microscopy of other direct openings, the vacuolar structures are con
normal eyes clearly reveals that the vacuoles are several sidered as having a significant role in the bulk outflow of
micrometres in size, are membrane-bound, and essentially aqueous humour across the endothelial barrier of
electron-optically empty; and when centrally located Schlemm's canal (Tripathi, 1971a,b; 1974).
within the cell tend to indent the nucleus (Fig. 2). The passage of fluid and particulate matter from
Serial section analyses reveal that at a given time the Schlemm's canal into the intra- and episcleral system of
majority of the vacuoles show a basal opening towards the collector channels, including the aqueous veins, is by
trabecular aspect ranging in size from 0-1 to 3-5 μπι. It is laminar flow.
therefore envisaged that, in life, the vacuoles are in direct
communication with the aqueous humour in the trabecular Lower Mammals
meshwork. A small proportion of vacuoles, however, In comparison to that of primates, the angle of the
show in addition apical (luminal) openings ranging in size anterior chamber in the lower mammals is not clearly
from 0*1 to 2-5 /xm and are thus interpreted as constituting defined, because the ciliary muscle is poorly developed and
a vacuolar transcellular channel (Tripathi, 1971a,b, is divided into two leaves, one of which lies against the
1974). inner aspect of the sclera while the other is continuous with
Using a variety of tracers (colloidal suspensions, graded the fibrous baseplate of the ciliary body. The resultant
microspheres, whole blood, etc.) introduced into the cleft is criss-crossed by fibrocellular strands (the trabecu-
anterior chamber at a physiological pressure, it can be lae), the most prominent of which extend from the root of
shown that the vacuoles readily become filled with tracer the iris to the inner aspect of the peripheral cornea and are
material (Tripathi, 1971a,b; 1974). Figure 4 shows the known as pectinate ligaments. The channels responsible
passage of an erythrocyte through a vacuolar structure. for the drainage of aqueous humour (the angular aqueous
