2011-2012 Basic and Clinical Science Course, Section 2: Fundamentals and Principles of Ophthalmology (Basic & Clinical Science Course)

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Fundamentals and Principles of Ophthalmology

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Basic and Clinical Science Course

Fundamentals and Principles of Ophthalmolog'y Section 2 2011-2012 ILast major revision 2009-2010)

t:l~ AMERICAN ACADEMY ~ OF OPHTHALMOLOGY Tile Eye M .D. A ssac;I1I;OI'

t""0NG EDUCATION ..,.""

o ",T"A lMOlDG 1\ 1'"

The Basic and Clinical Science Co urse is one component of the Lifelong Education for the Ophthalmologist (LEO) framework, which assists mem bers in planning their continu ing medical education. LEO includes an array of clinical education products that members may select to form individu alized, self-directed learning plans for updating their cl inical knowledge. Active members or fellows who use LEO components may accumulate sufficient CME credits to earn the LEO Award. Contact the Academy's Clinical Education Division for further information on LEO. The American Academy of Ophthalmology is accredited by the Accredi tation Council for Continuing Medical Education to provide continui ng medical education fo r physicians. The American Academy of Ophthalmology designates this enduring material for a maximum of 15 AMA PRA Category I Credits TM. Physicians should claim only credit commensurate with the extent of their participation in the activity.

The Academy provides th is material for educational purposes only. It is not intended to represent the only or best method or procedure in every case, nor to replace a physi cian's own judgment or give specific advice for case management. Including all ind ica tions, contraindications, side effects, and alternative agents for each drug or treatment is beyond the scope of th is materia l. All information and recommendations should be verified, prior to use. with current information included in the manufacturers' package inserts or other independent sources, and considered in light of the patient's condition and history. Reference to certain drugs. instruments, and other products in this course is made for illustrative purposes only and is not intended to constitute an endorsement of such. Some material may include information on applications that are not considered community standard, that reflect indications not included in approved FDA labeli ng, or that are approved for use only in restricted research settings. The FDA has stated that it is the responsibility of the physician to determine the FDA st atus of each drug or d evice he or she wishes to use, and to use them with appropriate. informed patient consent in compli ance with applicable law. The Academy speCifica ll y disclaims any and all liability for injury or other damages of any kind, from negligence or otherwise, for any and all claims that may arise from the use of any recommendat ions or other information contained herein.

Cover image tourtesy of Thomas A. Weingeist, PhD, MD.

Copyright © 20 11 American Academy of Ophthalmology All rights rese rved Printed in Singapo re

Basic and Clinical Science Course Gregory L. Skuta. MD. Oklahoma City. Oklaho ma. Senior Secretary for Clin ical Education Louis B. Cantor. MD. Indianapolis. Indiana. Secre tary for Ophthalmic Knowledge Jayne S. Weiss. MD. Detroit. Michigan. BCSC Course Cha ir

Section 2 Faculty Responsible for This Edition K. v. Chalam. MD. PhD. Chair. Jacksonville. Florida Balamurali K. Ambati. MD. Salt Lake City. Utah Hilary A. Beaver. MD. Iowa City. Iowa Sandeep Grover. MD. Jacksonville. Florida Lawrence M. Levine. MD. Jac ksonville. Florida Tony Wells. MD. Consultant. Wel lington. New Zealand Edward K. Isbey. III. MD. Asheville. North Carolina Practicing Ophthalmologists Advisory Comm ittee for Education

Financial Disclosures The authors state the followin g financial relationships: Dr Beaver: Genzyme. lecture honoraria recipient

Dr Wells: Alco n. consultant; Allergan. consultant The other authors state that they have no significant financial interest or other relation ship with the manufacturer of any commercial product discussed in the chapters that they contributed to this publication or wi th the manufacturer of any com peting commercial product.

Recent Past Faculty Gerha rd W. Cibis. MD Karla Johns. MD Shalesh Kaushal. MD. PhD James c. Tsai. MD [n addition. the Academy gratefully acknowledges the contributions of numerous past faculty and advisory committee members who have played an important role in the development of previous edi tion s of the Basic and Clinical Science Course.

American Academy of Ophthalmology Staff Richard A. Zorab, Vice Presidellt, Ophthalmic Kllowledge

Hal Straus, Director, Publications Departmelll Christine Arturo, Acquisitions Manager

Stephanie Tanaka, Publications Mallager D. Jean Ray, Production Mallager Brian Veen, Medical Editor Steven Huebner, Administrative Coordinator

a~ AMERICAN ACADEMY

\!:.J OF OPHTHALMOLOGV Till Ii>'c M.D. ".soc;IJI;OIl

655 Beach St reet Box 7424 San Francisco, CA 94120-7424

Contents General Introductio n

xv

Objectives . .

.1

PART I

Anatomy

1 Orbit and Ocular Adnexa Orbital Anatomy. . O rbital Vo lume. Bony Orbit . . O rbital Ma rgin . Orbital Roof . . Medi al Orbital Wall Orbital Floor. . . Lateral Orbital Wa ll Orbital Foramina, Ducts. Canals, and Fissures. Periorbital Sinuses. Cranial Nerves. Cilia ry Ganglion . . . Branches of th e Ciliary Gan glion Short C iliar y Nerves. . . Extraoc ular Muscles. Extraocular Muscle Insertions Extraocul ar Muscle Distribution in the Orbit. Extraoc ul ar Muscle O rigins. . . Blood Supply to the Extraocular Muscles. Innervation of the Extraocular Muscles Fine Structure of the Extraocular Muscles Eyelids ...... . Anatomy . . . . . . Vascular Supply of the Eyelids. Lymphatics of the Eyelids. . Accessory Eyelid Stru ctures. Lacr imal Gla nd and Excreto ry System. Lacrimal Gland. . . . . . Accessory Gla nds. . . . Lacrim al Excre tory System . Conjun ctiva . . . Tenon Capsule . . ..... Vasc ul ar Suppl y an d Drainage of th e O rbit . Posterior and Anterior Ciliary Arteries. Vortex Ve ins ......,....

3 .5 .5

.5 .5

.5 .5

.7 7 .9 10 12 13 14 15 16 16 16 18 18 18 21

21 22 22

29 30 31 32 32 33 33

34 35

36 36 38 v

vi • Contents

2 The Eye.

41

Topographic Features of the Globe Precorneal Tear Film .... .

41

Cornea . . . .

43 43 43 43 44

. ..... .

Characteristics of the Central and Peripheral Cornea. Epithelium and Basal Lamina. Nonepithelial Cells Bowman's Layer. . . . Stroma . . . .

Descemet's Membrane. Endothelium . Sclera. . . . .

Limbus . . Anterior Chamber

Trabecular Meshwork. Uveal Trabecular Meshwork Corneoscleral Meshwork. Perica nalicu lar Connective Tissue.

Schlemm Canal. Collector Channels Uveal Tract Iris. . . . . Stroma . .

Vessels and Nerves Posterior Pigmented Layer Dilator Muscle . Sph incter Muscle . . . Ciliar y Body . Ciliary Epithelium and Stroma Ciliary Muscle . . Choroid . . Bruch's Membrane.

Choriocapillaris . Lens . . . Capsule Epithelium. Fibers. . . Zo nu les (S uspensory Ligaments) Ret ina.

Retinal Pigment Epithelium Neurosensory Retina Macu la . . Ora Serrata Vitreous. .

42

45 45 46 47 48 50 53

54 54 54 54 54 55

56 56 58 58 60 61 61 61

63 64 64 66 67 68 70 70 70 71 71 73

79 82 82

Contents . vii

3

Cranial Nerves: Central and Peripheral Connections. . . . . . . Cranial Nerve I (Olfactory) . . Cranial Nerve II (O ptic Nerve) . In traocu lar Reg ion Intraorbital Region Intraca nal ic ular Region Intracranial Region . . Blood Suppl y of the Optic Nerve Chiasm . . . . . . . Optic Tract. Lateral Geniculate Body Optic Radiatio ns . Visual Corlex. . . . . Cranial Ne rve III (Oculomotor) Pathways for the Pupil Reflexes . Cranial Nerve IV (Trochlear). Cranial Ne rve V (Tri geminal) Mesencephalic Nucleus . Main Senso ry Nucle us . Spinal Nucleus and Tract. Moto r Nucleus . . . . . Divisions of Cranial Nerve V . Crani al Ne rve VI (Abd ucens). Cranial Ne rve VII (Facial) . Cavernous Sin us . . . Other Venous Si nuses . Circle of Wi llis .

PART II

4

Embryology .

Ocular Development Introducti on. Growth Factors. Homeobox Genes . Ne ural Crest Cells. Embryogenesis . Organogenesis of th e Eye Neurosensory Reti na Fovea . . . . . . . Retin al Pigmen t Epithelium O ptic Ne rve Lens . . . Vitreous.

87 87 87 89

91 93 93

94 96 96 96 96 97 97 99 99

· 100 100

100 100 102 \03

104 105 107 108 109

111 113 11 3 11 3

11 4 11 5 · 1J7

· 120 124 126 127 128 128 · 130

viii • Contents

Choroid . . . Cornea and Sclera. Anteri or Chamber, Angle, Iris, and Ciliary Body. Vascular System . . . . . . . Periocular Tissues and Eyelids Realignment of the Globe Congenital Anomalies. Genetic In fl uences Nongenetic Teratogens.

PART III

5

Genetics

· · · ·

132 133 135 137 139 140 141

141 141

145

Introduction.

147

Te rmin o logy. Glossa ry . . . . .

147 · 147

Molecular Genetics

165

Gene Structure. . . "Ju nk" DNA . . . . . . Ge ne Transcription. . . Transcription Factors and Regulation Intron Excision. . . . . . . . Alternative Splicing and Iso form s Methylation X-Inactivation . . . Imprinting . . . DNA Da mage and Repair Mutations and Disease . Requirements for Identifying a Disease-producing Mutation Mutations . . . . Cancer Genes. Mitochondrial Disease C hroni c Progressive Exter nal Ophth almoplegia. Leber Heredi ta ry Optic Neuropathy. . . . . Neuropathy, Ataxia, and Retinitis Pigmentosa. Other Mitochondrial Diseases . The Search for Genes in Specific Diseases . . . . Synteny . . . . . . . . . . Cytogenetic Markers (Mo rphologi call y Variant C hromoso mes) Gene Dosage . Association. . . . . . . . ....... Linkage. Ca ndidate Gene Approaches Mutat ion Screening. DNA Libraries . . Single-stranded Conformat ional Pol ymorphism

165 165 166 166 · 168 168 168 168 169 169 170 170 170 · 17 1 173 174 175 175 176 176 176 177 . 177 177 177 180 182 182 182

Contents. ix

Denaturing G radient Gel Electrophoresis Direct Sequencing . . . . . . . Use of Restriction Endonucleases

Allele-specific Oligonucleotides . Gene Therapy . . . . . . . . . . Replacement of Absent Gene Product in X-Linked and Recessive D isease. . . , Strategies for Dominant Diseases

6

Clinical Genetics . . . . . Terminology: Hereditary, Genetic, Fam ili al, Co ngen ital Genes and Chromosomes

Alleles. M itosis . . Meios is . .

Segregation Independent Assor tment Linkage . . . . . . . Chromosomal Analysis Indications. . . . Preparation. . . .

Aneuploidy of Autosomes Mosaicism.

. ....

Eti ology of Chromosomal Aberrations. Mutations . . .

Polymo rph isms . . . . . Ge no me, Ge notype, Phenotype . Single-Gene Disorde rs. Va ri ab ility Penetrance .

Expressivity Pleiotropism Racial and Ethnic Concentration of Genetic Disorders. Patterns of Inheritance . . . . . . Recessivity Versus Dominance . . Autosomal Recessive Inheritance . Autosomal Dominant Inheri tance.

· · · · ·

183 184 184 184 184

187 188

191 191 193 194 195

195 196 196

197 197 198 198 199 .203 .204 .207 .207 · 208 .208 · 208 · 209 · 209 .210 · 210 · 2 11 .211 · 212 · 216

X- Linked Inheritance

· 218

Maternal Inheritance . . . . . .

.220 · 220 · 224

Lyonization . . . . .

Polygenic and Multifactorial Inheritance. Pedigree Analys is. . .... Ge netic Co unseling. . . . . . Iss ues in Genetic Co unseling Prenata l Diagnosis

.225 · 226 · 227 · 228

x • Contents Pharmacogenetics . . . . . . . . . . Clinical Management of Genetic Disease. Accurate Diagnosis . . . . . . . . Complete Explanation of the Disease Treatment of the Disease Process . .

Ge netic Counseling. . . . . . . . Referral to Providers of Support for Disabi lities.

PART IV

Biochemistry and Metabolism .

Introduction.

7

.229 .230 · 230 .230 .230 .232 · 232

233 235

Tear Film . .

237

Lipid Layer . . Aq ueous Layer . Mucin Layer. .

.237 .239 .24 1 · 24 1 .244

Tear Secretion .

Tear Dysfunction.

8 Cornea ...

247

Epithelium . . .

Descemet's Membrane and Endotheliulll .

· 248 .249 .249 .25 1

Iris and Ciliary Body . . . . . .

253

Introd uction . . . . . . Protein Types Expressed in Human Cil iary Body Iris-Ciliary Body Smooth Muscle. Aq ueous Humor Dynamics Eicosanoids . . . . . Types and Actions. Synthesis. . . . . Leukotrienes. . . Prostaglandin Receptors. Neurotransmitters. Receptors. and Signal Transduction Pathways. Miotics . . . . . . . . . . . . . . . Mydriatics. . . . . . . . . . . . . . . . . . . Calcium Channels and Channel Blockers. . . . . . Membrane Receptors and lntracellular Commun ications . Signal Transduction. . . . . . . . . . . . . Receptor-Effector Coupling . . . . . . . . . Cyclic AMP and Polyphosphoinos itide Turnove r Receptors . . . . . . . . . . . . . . . . . . .

· 253 . 253 . 253 . 254 . 255 . 255 . 257 . 258 . 258 . 258 . 259 . 260 . 26 1 .26 1 . 26 1 . 26 1 . 262 . 264

Bowman's Layer Stroma . . . .

9

Contents . xi

10 Aqueous Humor . . Aqueous Dynamics. . . Composition of the Aq ueous Humor Inorganic Ions . Organic Anions.

Carbohydrates Glutathione and Urea Prote ins . . . . . .

Growth -Modulator y Factors Vascula r Endothelial Growth Factors Oxygen and Carbon Dioxide . . . . Clinical Implications of Breakdown of the Blood-Aqueous ' Barrier

11 Lens ..

265 · 265 .265 .267 · 267 .268 · 268 .268 .270 · 27 1 · 27 1 .272

273

Structure of th e Lens Capsule Epithelium. . Cortex and Nucleus. Chemical Composition of the Lens

Membranes . . . Lens Proteins. ....,. Physiologic Aspects . . . . . . . Lens Metabolism and Formation of Sugar Cataracts. Energy Production . Carbohyd rate Cataracts

· 273 · 273 .274 · 274 .275 · 275 · 275 .277 .278 .278 · 279

12 Vitreous .

283

Composition .

· 283 · 283 · 284 .285 · 286 · 286 · 286 .287 .287 · 287 .288 .288 · 288 .289

Collage n . Hyaluronan Soluble and Fibril-Associated Proteins . Zonular Fibers, Lipids, and Low-Molecular-Weight Sol utes. Biochemical Changes Wi th Aging and Disease . . . . . . Vitreous Liquefact ion and Pos terio r Vitreous D etachme nt

Myopia

............ .

Vitreous as an Inhibitor of Angiogenes is . .

Physiologic Changes After Vitrectomy . Injury With Hemorrhage and Infl ammati on Invo lvement of Vitreo us in Macu lar Hole Formation. Ge netic D isease InvolVing the Vit reous.

Enzymatic Vitreolysis

13 Retina ... . Neu ral Retina-T he Photoreceptors. Rod Photo transduction . Cone Phototransdu ction .

291 · 29 1 · 29 1 · 293

xii. Conte nts

Rod-Specific Ge ne Defects. Cone- and Rod-Specific Ge ne Defects Cone-Specific Gene Defects . RPE-Spec ific Gene Defects. . Ubiquitously Expressed Genes Causing Retinal Degenerations In ne r Nuclear Layer . Retinal Electrophysiology . . . .

14 Retinal Pigment Epithelium . Anatomical Description.

Biochemical Composition Protein s

Li pids . . Nucleic Acids. . . . Major Physiologic Roles of the RPE . Visual Pigme nt Regene ration . Phagocytosis of Shed Photoreceptor Outer-Segment Discs Transport . . . Pigmentation. . Retinal Ad hesion The RPE in Disease.

15 Free Radicals and Antioxidants Cell ular Sources of Active Oxygen Species Mechanisms of Lipid Peroxidation . Oxidative Damage to the Lens . . . . . Vulnerability of the Retina to Free Rad icals. Antioxidants in the Reti na and RPE. . . . Selenium, Gl utathione, Glu tathione Peroxidase, and Glutat hione-S-Transferase. Vitamin E . Superoxide Dismutase and Catalase Ascorbate Carotenoids .

PART V

O~ular

Pharmacology .

16 Pharmacologic Principles Introduction. . . . . . Pharmacok in etics.

Pharmacodynamics. Pharmacotherapeutics.

Toxicity . . Pharmacokinetics: The Route of Drug Delivery . Topical Administ rat ion Local Administrat ion Systemic Adm inistra tio n.

Methods of Ocular Drug Design and Delivery. Pharmacodynamics: The Mechanism of Drug Ac tion

. . . . . . .

295 296 296 297 298 298 301

303 · 303 .304 .304 · 305 · 305 · 305 · 305 · 306 · 307 .307 .308 · 308

311 · · · · ·

311 3 12 313 3 15 316

· · · · ·

3 16 317 317 317 318

319 321 · 32 1 · 322 · 322 · 322 · 322 .323 .323 · 327 · 328 · 330 · 33 1

Contents . xiii

17

Ocular Pharmacotherapeutics .

333

Legal Aspects of Medical Therapy. Cholinergic Agents . . Muscarinic Drugs. Nicotinic Drugs. . Adrenergic Agents . . a-Adrenergic Agents p-Adrenergic Agents Ca rbonic Anhydrase Inhibitors. Prostaglandin Analog ues Combined Medications Osmotic Agents Actions and Uses Agents . Anti -Inflammatory Agents. Glucocorti coids. . . . Nonsteroidal Anti-Inflammatory Drugs Mast-Cell Stabilizers and Antihistamines . Antifibrotic Agents . . . . . Antibiotics . . . . . . . Penicillins and Ce phalosporins Other Ant ibacterial Agents. Antifungal Agen ts. An tiviral Agents . Medications for AcarItharnoeba Infections Local Anesthetics. Topical Anest hetics in Anterior Segment Surgery Purified Ne urotoxin Complex Medications for the Dry Eye Hyperosmolar Agents. Ocular Decongestants. Irrigating Solutions. Diagnostic Agents Viscoelastic Age nts Fibrinolyt ic Agents Thrombin . . Antifibrinolytic Agents Corneal Storage Medium Vitam in Supplements and Antioxida nts Interferon Growth Factors.

.333 · 334 · 335 · 342 .344 .345 .348 · 351 .354 · 355 · 355 · 355 · 355 · 356 .357 · 361 .364 · 366 · 368 · 368 · 37 1 · 378 .380 · 385 · 386 · 389 · 390 · 390 · 391 .392 .392 .392 .393 · 393 · 393 · 394 · 394 · 395 .395 .395

Basic Texts. . . Related Academy Materials Credit Reporting Form Study Questions Answers. Index . . . . .

· 399 · 401 .403 .407 .414 · 417

General Introduction The Basic and Clinical Science Course (BCSC) is designed to meet the needs of residen ts and practitioners for a comprehensive yet concise curriculum of the field of ophthalmology. The BCSC has developed from its original brief outline format. which relied heavily on outside readings. to a more convenient and educationally useful self-contained text. The Academy updates and rev ises the course annually. with the goals of integrating the basic science and clinical practice of ophthalmology and of keep ing ophthalmologists current with new developments in the various subspecialties. The BCSC incorporates the effort and expertise of more than 80 ophthalmologists. organ ized into 13 Section facu lties. wo rking wi th Academy editorial staff. [n addition. the course continues to benefit from many lasting contributions made by the facul ties of previous ed itions. Members of the Academy's Practicing Ophthalmologists Advisory Committee for Education serve on each facu lty and, as a group. review every volW11e before and after major rev isio ns.

Organization of the Course The Basic and Cli nica l Science Course comprises 13 volumes. incorporating fu ndamental ophthalmic knowledge. subspecialty areas. and special topics: 2 3 4 5 6 7

Update on General Medicine Fundamentals and PrinCiples of Ophthalmology Clinical Optics Ophthalmic Pathology and [ntraoc ular Tumors Ne uro-Ophthalmology Pediatric Ophthalmology and Strabismus Orbit. Eyelids. and Lacrimal System

8 External Disease and Cornea

9 Intraocular In flammation and Uveitis 10 Glaucoma II Lens and Cataract 12 Retina and Vitreous 13 Refractive Surgery In addi tion. a comprehensive Master Index allows the reader to easily locate subjects throughout the entire series.

References Readers who wis h to explore specific topics in greater detail may consult the references cited within each chapter and listed in the Basic Texts section at the back of the book. T hese references are intended to be selective rather than exh austive. chosen by the BCSC facu lty as being important. current. and readily available to residents and practitioners. xv

xvi . Ge nera l Introductio n

Related Academy educational materials are also listed in the appropriate sections. They include books, o nline and audiovisual materials, self-assessment programs, clinical modules, and interactive programs.

Study Questions and CME Credit Each volume of the BCSC is designed as an independent stud y activity for ophthalmology residents and practit ioners. The learning objectives for this vol ume are given on page 1. The text, illustrations, and references provide the information necessary to achieve the objectives; the study qu estions allow readers to test their unde rstanding of the material and their mastery of the objectives. Physicians who wish to claim CME credit for this educational activity may do so by ma il, by fax, or online. The necessary forms and instruct ions are given at the end of the book.

Conclusion The Basic and Clinical Science Course has expanded greatly over the yea rs, with the addition of much new text and numerous iLlustrations. Recent editions have sought to place a greater emphas is on clinical applicability while maintaining a solid fo undation in basic science. As with any educational program, it reflects the experience of its authors. As its faculties change and as medicine progresses, new viewpoints are always emerging on controversial subjects and tech niques. Not all alternate approaches can be included in this series; as with any educational endeavor, the learn er should seek additional sources, including such carefully balanced opinions as the Academy's Preferred Practice Patterns. The BCSC faculty and staff are continuously stri ving to improve the educational usefulness of the course; you, the reader, can contribute to this ongoing process. If you have any suggestions or questions about the series, please do not hesitate to contact the faculty or the editors. The authors, editors, and reviewers ho pe that yo ur stud y of the BCSC wi ll be oflasting value and that each Section will serve as a practical resource for quality patient care.

Objectives Upon completion of BCSC Secti o n 2, Fundamentals and Prin ciples of Ophthalmology, the reader should be able to identify the bones making up the orbital walls and the orbital foramin a

identify the o rigi n and pathways of cranial nerves 1- VII

• identify the origin and insertions of the extraocu lar muscles and use CT and MRI studies to point out the extraocular muscles, optic nerve, and lacrimal gland in axial and coronal views of the orbit describe the distribution of the ar terial and venous circulat ions of the orbit and optic nerve

summari ze the structural -fun cti onal relationships of the outflow pathways for aqueous humo r of the eye

• deli neate the events of early embryogenesis that are importa nt for the subsequent development of the eye and orbit • identify the roles of growth factors, homeobox ge nes, and neural crest cells in the ge nesis of the eye describe the sequence of events in the differentiatio n of the ocu lar tissues during embryo nic and feta l development of the eye • describe the stages in the development of the eye and the correlat ion between congenital ocular disorders and the timing of an insult to the embryo

describe the organization of the human genome and the role of genetic mutations in health and d isease

explain how DNA can be manipulated in the laboratory to map and to clone genes, to identify genes from surrounding DNA, and to create transgenic and knockout animals

demonstrate how appropriate diagnosis and manage ment of genet ic diseases can lead to better patient care

assess the role of th e ophthal mologist in the provision of genetic co unselin g

identify th e biochemical comp ositi on of the various parts of the eye and the eye's secretions discuss new concepts regarding the in teraction between membrane prote in s and G proteins and the effects of thi s in te ractio n o n ocular functions, such as rhodopsin w ith tran sducin in the convers ion of "light-stimulus" to "electric-

signal" • discuss the biochem ical derangements in diabetes mellitus

and the way in which they lead to the disease's oc ul ar compli cat ions. such as diabetic retinopathy and cataract formation

list th e var ied functions of th e retinal pigment epithelium such as phagocytosis and vitamin A metabolism and their relationship to retinal diseases

summari ze the role of free radicals and antioxidants

• describe the features of th e eye that facilitate or impede drug delivery ci te the basic principles underlying the use of autonomic therapeutic agents in a variety of ocular cond ition s • list the indicat ions. co ntraindications, mechanis ms of acti on, and side effects of var io us drugs in the management of

glaucoma describe th e mechanisms of action of antibiotics, antivirais , and antifungal med icati ons: their indications, dosages, and side

effects discuss the anesthetic agents used in ophthalmology, th eir dosages and adverse effects discuss therapeut ic drugs on the horizon and in the process of bein g in trod uced into clinical practice in the imm ediate future

CHAPTER

1

Orbit and Ocular Adnexa

Orbital Anatom Orbital Volume The eyes lie within 2 bony orbits; the volu me of each adult orbit is slightly less than 30 cm 3 . Each orbit is pear-sha ped. with the optic ne rve representing the stem . The o rbital ent rance averages about 35 mm in height and 45 mm in width . The maximu m width is located abo ut I cm behind th e ante rio r orbital margin. In adu lts. the depth of the o rbit varies from 40 to 45 mm from th e o rbital ent rance to the orbital apex. Both race an d sex affect each of these measurements.

Bony Orbit Seven bones make up the bony orbit (Fig I - I ; see also Fig 1-5): I. 2. 3. 4. 5. 6. 7.

fro ntal zygo matic maxi lla (o r max illary bo ne) ethmoid (or ethmoidal bone) sphenoid lacr imal palatine

Orbital Margin T he orbital margin forms a quadr ilate ral spiral (Fig 1-2) whose superior margin is formed by the fro ntal bo ne. which is in terrupted mediall y by the supraorbita l notch. The med ial margin is formed above by the fro nta l bone and below by the posterior lacrimal crest of the lacrimal bone and the anterior lacrima l crest of the maxillary bone. The inferior margin derives from the maxi llary and zygomati c bones. Laterally. the zygomatic and frontal bones complete the rim.

Orbital Roof The orbital roof is for med from both the orbital plate of the frontal bone and th e lesser wing of the sphenoid bone (Fig 1-3). The fossa for the lacrimal gland. lying anterolaterally

5

6 • Fun dame nta ls and Principles of Opht halmology Frontal

Supraorbital foramen

~

Greater wing of sphenoid

~

/

....

Superior orbital ridge Supraorbital notch Superior orbital fissure Optic foramen

Inferior

orbital fissure

,,::::.--.+=_

Lesser wing of

sphenoid Ethmoid

;:;''l-~.--~~

Lacrimal bone and fossa

Zygomatic Maxilla

Infraorbital foramen

Figure 1-1

Frontal view of bony right orbit

(Reproduced with permission from Doxanas MT, Anderson RL.

Clinica l Orbital Anatomy. Baltimore: Williams & Wilkins; 1984.)

Posterior lacrimal

crest

Anterior lacrimal

crest

Figure 1-2 Right orbital margin. The orbital rim forms a quadri lateral spiral (arrows). Note the relationship between the anterior lacrimal crest of the maxillary bone and t he posterior lacrimal crest of the lacrimal bone. (Reproduced with permission from Doxanas MT. Anderson RL. Clin ical Orbital Anatomy. Baltimore: Williams & Wilkins; 7984.)

CHAPTER 1:

Orbit and Ocu lar Adnexa .

7

Supraort,;!a! foramen

Area of the lacrimal fossa

Cribra orbitalia

Orbital plate of frontal bone Ethmoidal sinuses

W'hlF--

Lesser wing of sphenoid bone Optic foramen

Superior orbital fissure

Figure 1·3

View from below, looking up into the orbital roof (superior orbital wall). (Reproduced with permission from Doxanas MT, Anderson RL. Clinical Orbital Anatomy. Baltimore: Williams & Wilkins; 1984.)

behind the zygo matic process of the frontal bone. resides within the orbital roof. MediaUy. the trochlear fossa is located on the fronta l bone approximately 4 mm from the orbital margi n and is the site of the pu lley of the superior oblique muscle. where the trochlea. a curved plate of hyali ne cartilage. is attached. Helveslon EM, Merriam WW, Ellis FD, Shellhamer RH , Gosli ng CG. The trochlea. A study of the anatomy and physiology. Ophthalmology. 1982;89(2): 124- 133.

Medial Orbital Wall T he medial wall of the o rbit is formed from 4 bones (Fig 1-4): I. 2. 3. 4.

fronta l process of the maxilla lacr imal bone orbital plate of the ethmoid lesser wing of the sphenoid

The ethmoidal bone makes up th e largest portion of the m edial wall. The lacrimal fossa is formed by the fro nta l process of the maxillary and the lacrimal bone. Below. the lacrimal fossa is cont inuous with the bony nasolacrimal cana l, which extends into the inferior meatus (the space beneath the in ferior turbinate) of the nose. The paper-thin structure of the med ial wa ll is reflected in its name, lamina papyracea .

Orbital Floor The floor of the orbit. which is the roof of the maxillary antrum. o r sinus. is composed of 3 bones (Fig 1-5): 1. maxilla

8 • Fundamentals and Principles of Ophthalmology

Orbital plate of frontal bone

Ethmoid

Ethmoidal foramina Lesser wing of sphenoid Optic foramen

Lacrimal bone

lacrimal fossa Fossa for inferior oblique muscle

Pterygopalatine foramen and fossa

Figure 1-4

Rig ht medial orbital wall as viewed from lateral side .

(Reproduced with permission from

Doxanas MT, Anderson RL Cl inica l Orbital Anatomy. Baltimore: Williams & Wilkins; 1984.)

Nasolacrimal canal Orbital aspect of maxillary bone

Infraorbital groove

Ethmoidal ~Y'­ sinuses

Palatine

Right orbita l floor and inferior orbital fissure. (Reproduced with permission from Doxanas MT; Anderson RL. Clinica l Orbita l Anatomy. Baltimore: Williams & Wilkins; 1984.)

Figure 1-5

CHAPTER 1:

Orbit and Ocular Adnexa.

9

2. palatine 3. orbital plate of the zygo matic The infraorbital groove traverses th e fl oor and descends anteriorly into a canal. It exits as

the infraorbital foramen. below the orbital margin of the maxillary bone. Arising from the floor ofthe orbit just lateral to the opening of the nasolacrimal canal is the inferior oblique muscle. the onl y extraoc ular muscle that does not originate from the orbi tal apex. The floor of the orbit slopes downward approximately 20 0 from posterior to anterior.

Lateral Orbital Wall The thickest and strongest of the orbital walls. the lateral wa ll of the orbit is formed from 2 bones (Fig 1-6): the zygomatic and the greater wing of the sphenoid. The lateral orbital tubercle (the Whilnall tuberc/e). a small elevation of the orbital margin of the zygomatic bone. lies approximately II mm below the frontozygo matic suture. This important landmark is the site of attachment for the following: • check li gament o f th e lateral rectus muscle

suspensory ligament of the eyeball (Lockwood suspensory ligament) lateral palpebral ligament apo neurosis of the levator muscle

Whitnaliliga ment

Orbital plate of frontal

Greater wing of sphenoid Superior orbital fissure

Zygomatic--+--

Inferior orbital fissure

Figure 1-6

Right lateral orbital wa ll as vi ewed from medial sid e. (Reproduced with permission from Doxanas MT. Anderson RL. Clinical Orbital Anatomy. Baltimore: Williams & Wilkins; 1984.)

10 • Fundamentals and Princi ples of Ophthalmology

Orbital Foramina, Ducts, Canals, and Fissures Foramina The optic foramen leads fro m the middle cranial fossa to th e apex ofthe orbit. It is directed fo rward, laterally, and somewhat downward and condu cts the optic nerve, the ophth almic artery, and sympathetic fibers fro m the carotid plexus (Fig 1-7). The optic foramen passes through the lesser wing of the sphenoid bone. The supraorbital foramen (in some people, it is a n otch instead of a foramen) is located at the m edial third of the sup erior margin of the orbit. It transmits blood vessels and th e supraorbital nerve, which is a branch of the ophthalmic division (VI) of cranial nerve V (eN V, trigeminal). The anterior ethmoidal foramen is located at the fron toeth moidal suture and transmits the anterior ethmoidal vessels and nerve. The posterior ethmoidal foramen lies at the junction of the roof and the

medial wall of the orbit and tran smits the posterior ethmoidal vessels and nerve through the fronta l bone. The zygomatic foramen lies in the lateral aspect of the zygomatic bone and contains zygomaticofaciaJ and zygomaticotempo ral branches of th e zygomatic nerve

and the zygomatic artery.

Nasolacrimal duct The nasolacrimal duct travels inferiorly fro m the lacrimal fo ssa into the inferior meatus

of the nose.

Infraorbital canal The infraorbital canal continues anteriorly from th e inf rao rbital groove and exits 4 mm below th e in fer ior orbital margin . where it tran smits the in fraorb ital nerve, which is a

branch of V, (the maxillary division of eN V).

Fissures The superior orbital fissure (Fig 1-8) is located between the greater and the lesser wings of the sphenoid bone an d lies below and lateral to the optic foramen. It is ab out 22 mm long and is spanned by the common tendinous rin g of the rectus muscles (annulus of Zinn). Above the ring, the su perior orbital fissure transm its the lacrimal nerve of eN V I frontal nerve of eN V I eN IV (trochlear) superior ophthalmic vein

Within th e ring or between the 2 heads of th e rectus muscle are the following: superior and inferior divisions of eN III (oc ulomotor) nasociliary branch of eN V I sympathetic roots of the ciliary ganglion eN VI (abducens) Occasionally, the inferior ophthalmic vein is below the ring. The inferior orbital fissure lies just below the superior fissure between the lateral wall and the floor of the orbit, givi ng access to the pterygopalatine and in ferote mporal fossae. Hence, it is close to the fora men rotundum and the pterygo id canal. It transmits the

CHA PTER 1:

Orbit and Ocu lar Adnexa . 11

A

c

E

Figure 1-7 Series of axial computed tomography (CT) scans. Each compares tissue and corresponding bone-window density through the optic canal (DC) and superior orbital fissure (SOF). The SOF passes above and below the plane of the OC and is commonly mistaken for the ~C . The OC lies in the same plane as the anterior clinoid processes (Ac/in) and may be cut obliquely in scans so that the entire canal length does not always appear in 1 section . Four differen t planes of section are shown in this series: A-B, Plane 1 is below the canal; C-D, Plane 2 is iust under the canal; E-F, Plane 3 is at the canal; G-H, Plane 4 is iust at the top of and above t he canal.

12 • Fundamentals and Principles of Ophtha lmology Lacrim al branch of

eN v 1

Superior orbital fissure

Frontal branch of CN V1 Superior ophthalmic ve in

Trochlear nerve (C N IV) Superior rectus Levator palpebrae superioris

:'-_ - Superior oblique

Medial rectus

~~~r;z:-t- Optic nerve Ophlhalmic artery Nasociliary branch of CN V1 Inferior rectus

Inferior ophthalmic vein Abducens nerve

Oculomotor nerve (C N III divisions 1 and 2)

(CNVI ) Figure 1-8

Structures pass ing through the supe rior orbital fissure. (From Bron AJ, Triparhl Re. Tflparhi

BJ. Wolff's Anatomy of the Eye and Orbit. 8th ed. London: Chapman & Hall; 1997.)

infrao rbital a nd zygomatic branches of eN V" an o rbital nerve from the pterygopalatine ganglion, and the inferior ophthalmic vei n. The inferior ophthalmic vein con nects with the pterygoid plexus before the vein drains into th e cavernous sinus.

Periorbital Sinuses The pe ri orbital sinuses have a close anatomical relationship with th e orbits, whi ch a re located o n either side of th e root of the nose. The medial walls of the orbits, whi ch border the nasal cavity ante riorly and the ethm o idal sin us (see Fig 1-3) an d th e sphenoid sinus posteriorly, are almost parallel. In th e adu lt, the lateral wall of each orbit for ms an angle of approximately 45" with the medial plane. The lateral walls border th e middle crani al, temporal, and pterygopalatine fossae. Superior to th e orbit are the ante rior cranial fossa and the fro ntal sin us. The maxi llary sinus and the palatine air cells are located inferio rly. The peri orbital sinuses offer a route for the spread of infection. Mucoceles occasionall y arise fro m the sinuses, extend into the adjacent orbit, and may confuse the clinician

CHAPTER 1:

Orb it and Ocu la r Adnexa. 13

in the d ifferential diagnosis of orbital tumo rs. The locations of the paranasal air sinuses and their relation to anatomical features of the skull are shown in Figures 1-9 and 1-10. Figure 1-9 also shows the distribut io n of pain originating from sinusitis. See BCSC Section 7, Orbit, Eyelids, and Lacrimal System, fo r further discussion. Doxanas M1: Anderson RL. Clinical Orbital Atlatomy. Baltimore: Williams & Wilkins; 1984:232. Z ide BM. Surgical Anatomy Around th e Orbit: The System of Zon es. Philadelphia: Lipp incott W illiams & Wilkins; 2005.

Cranial Nerves Six of the 12 cranial nerves (CN 11- VII ) d irectly innervate the eye and periocular tissues. Because certain tumors affecting CN I (olfactory) can give rise to important ophthalmic signs and symptoms, familiarity with the anatomy of this nerve is also important for the ophthalmologist. (C hapter 3 discusses the central and peripheral connections of CN I -V I!. ) See also BCSC Section 7, Orbit, Eyelids, and Lacrimal System.

Area of pain in frontal

Area of pain sphenoethmoidal

Figure 1-9 A , Bones of the face, showing regions where pa in is experienced in sinusitis . B, Pos itions of th e paranasal sinuses relative to the face. (Reproduced with permission from Snell RS, Lemp MA Clinical

A

Anatomy of the Eye. Boston: Blackwell; 1989.)

/ - Frontal sinus Ethmoidal

Cl::§~~~'Tsinuses Sphenoid sinus Maxi llary sinus

B

14 • Fundamenta ls and Principles of Ophthalmology Crista galli ,>~""""c-- Facial

nucleus

intermedius

I CNVI

Figur. 3-1 2

Cross section of the pons at the level of the CN VI (abducens) nucleus. CS =

corticospinal tract, MLF = medial longitudinal fascicu lus, PPRF = pontine pa ramedian reticular formation. (//{ustrat;on by Sylvia Barker.)

CHAPTER 3:

Cranial Nerves: Central and Peripheral Connections •

105

below and lateral to the carotid artery and may transiently carry sympathetic fibers from the carotid plexus. It passes through the superior orbital fissure within the annulus of Zinn and innervates the lateral rectus muscle on its ocular surface.

Cranial Nerve VII (Facial) Cranial nerve VII is a complex mixed sensory and motor nerve. The motor root contains special visceral efferent fibers that innervate the muscles of facial expression. The so-called sensory root ofCN VII is the nervus intermedius, which contains special visceral afferent, general somatic afferent, and general visce ral efferent fibers. The special visceral afferent fibers, which convey the sense of taste from the ante rior two thirds of the tongue, terminate centrally in the nucleus of the tractus solitarius. The general somatic afferent fibers convey sensation from the external auditory meatus and the retroauricular skin; centrally, they enter the spinal nucleus of CN V. The general visceral efferent fibers provide preganglioniC parasympathetic innervation by way of the sphenopalatine and submandibular ganglia to the lac rimal, submaxillary, and sublingual glands. The motor nucleus ofCN VII is a cigar-shaped column, 4 mm long, located in the caudal third ofthe pons. It is ventrolateral to the CN VI nucleus, ventromedial to the spinal nucleus of CN V, and dorsal to the superior olive. Four distinct subgroups within the nucleus innervate specific facial muscles; the ventral portion of the intermediate group probably supplies axons to the orbicularis oculi. The part of the nucleus supplying the upper half of the face receives corticobulbar input from both cerebral hemispheres. The lower half of the face is influenced by corticobuloar fibers from the opposite cerebral hemisphere. Fibers from the motor nucleus course dorsomedially to approach the floor of the fourth ventricle and then ascend immediately dorsal to the CN VI nucleus. At the rostral end of the CN VI nucleus, the main facial motor fibers arch over its dorsal surface (forming the internal genu of CN VII) and then pass ventrolaterally between the spinal nucleus of CN V and the CN VII nucleus to exit the brainstem at the pontomedullary junction. The bulge formed by the CN VII genu in the floor of the fourth ventricle is the facial colliculus (Fig 3-13). The sensory nucleus of CN VII is the rostral portion of the tractus soli tar ius, sometimes known as the gustatory nucleus. It lies lateral to the motor and parasympathetic nuclei in the caudal pons. Sensations of taste from the anterior two thirds of the tongue are carried by special visceral afferent fibers to this nucleus. The impulses travel along the lingual nerve and chorda tympani; the cell bodies for these impulses are located in the gen iculate ganglion. They eventually reach the brain through the nervus intermedius. Cranial nerve VII, the nervus intermedius, and CN VIII (acoustic) pass together through the lateral pontine cistern in the cerebellopontine angle and enter the internal auditory meatus in a common meningeal sheath. Cran ial nerve VII and the intermedius nerve then enter the fallopian canal, the longest bony canal traversed by any cranial nerve (30 mm). Cranial nerve VII can be divided into 3 segments in its course through this canal. After passing ante rolaterally for a short distance known as the labyrinthine segment, the nerves bend sharply at the geniculate ganglion and are then directed dorsolaterally past the tympanic cavity. This 90° bend, known as the tympanic segment, is the external genu of

106 • Funda me ntals and Principles of Ophthalmology Mesencephalic nucleus 01V M!lin sensory nucleus 01V

Lac rima l ref lex arc (after Ku rihashil. The affe rent pathway is provided by the first and second divisions of CN V. The efferent path proceeds from the lacrimal nucle us (close to the supe rio r salivary nucleusl via CN VII (nervus intermedius!. through the geniculate gang lion,

Figur.3-13

th e greater superficia l petrosa l nerve, and the nerve of th e pterygoid canal (where it is joined

by sympathetic fibers from the deep petrosa l nervel. The nerve passes to the pterygopalatine ganglion, where it synapses w ith postganglionic fibers . These fibers reach the lacrimal gland directly, via the retro-orbital plexus of nerves. The fibers carry cholinergic and vasoactive intestinal polypeptide (VIP)-ergic fibers to the gland. (From Bron Ai Triparhi RC, Tripathi 8J. Wolff's Anatomy of the Eye and Orbit. 8th ed. London: Chapman & Hall; 1997.)

CN VII. Two parasympathetic branches fro m the superior salivatory and lac rimal nuclei leave the nerve at the tympanic segment: the greater superficial petrosal nerve and a small filament that joins the inferior petrosal nerve, The third segment. the mastoid segment. of the nerve is directed straight down toward the base of the skulL The stapedius nerve leaves. and the chorda tympani joins CN VII in the mastoid segment. The CN VII trunk then exits the skull at the stylomastoid foramen and separates into a large temporofacial and a small cervicofacial division between the superficial and deep lobes of the parotid gland. This area of branching is known as the pes anserinus. The temporofacial division gives rise to the temporal. zygomatic. and buccal branches, The cervicofacial division is the origin of the marginal mandibular and colli branches, However. anastomoses and branching patterns are numerous, Commonly. the temporal branch supplies the upper half of the orbicularis oculi. and the zygomatic branch supplies the lower half. The fro ntalis. corrugator supercilii. and pyramidalis muscles are usually innervated by the temporal branch. The parasympathetic outflow originates in the superior salivatory nucleus and the lacrimal nucleus. both of which lie posterolateral to the motor nucleus and which probably receive afferent fibers from the hypothalamus, The superior salivatory nucleus also receives input from the olfactory system. The hypothalamic fib ers reaching the lacrimal nucleus may mediate emotional tearing. and there is supranuclear input from the cortex

CHAPTER 3,

Cranial Nerves: Central and Peripheral Connections.

107

and the limbic system. Reflex lacrimation is controlled by afferents from the sensory nuclei of eN V. These preganglionic parasympathetic fibers pass peripherally as part of the nervus intermedius and divide into 2 groups near the external genu of eN VII. The lacrimal group of fibers passes to the pterygopalatine ganglion in the greater superficial petrosal nerve. The salivatory group of fibers projects through the chorda tympani nerve to the submandibular ganglion to innervate the submandibular and sublingual salivary glands. The greater superficial petrosal nerve extends forward on the anterior surface of the petrous temporal bone to join the deep petrosal nerve (sympathetic) and form the nerve of the pterygoid canal. This nerve enters the pterygopalatine fossa; joins the pterygopalatine ganglion; and gives rise to unmyelinated postganglionic fibers that innervate the globe, lacrimal gland, glands of the palate, and nose. Those parasympathetic fibers destined for the orbit enter it via the inferior orbital fissure. Here, they are joined by sympathetic fibers from the carotid plexus and form a retro-orbital plexus of nerves, whose rami oculares supply orbital vessels or enter the globe to supply the choroid and anterior segment structures. Some of these fibers enter the globe directly; others enter via connections with the short ciliary nerves. The rami oculares also supply the lacrimal gland.

Cavernous Sinus The cavernous sinus is an interconnected series of venous channels located just posterior to the orbital apex and lateral to the sphenoidal air sinus and pituitary fossa (Fig 3-14). The following structures are located within the venous cavity: • the leA surrounded by the sympathetic carotid plexus • eN III, eN IV, and eN VI • the ophthalmic and maxillary divisions of eN V

:-.---

=~;,,~n~~2{C)PhllhallmiC artery . =~--.....

Sphenoid sinus Sphenoid sinus

A

B

Figur.3-14 Cavernous sinus, corona l sections (A) at the level of the pituitary fossa and (S) at the level of the anterior clinoid process. leA = internal carotid artery, ON = optic nerve. (Repro. duced by permission from Doxanas MT. Anderson RL. Clinical Orbita l Anatomy. Baltimore: W illiams & W ilkins; 1984.)

108 • Fundamentals and Principles of Ophthalmology

Other Venous Sinuses The cavernous sinus is only 1 part of an interconnecting series of venous channels that carry blood away from the brain and drain into the internal jugular veins. Other venous sinuses include the superior sagittal, transverse, straight, sigmoid, and petrosal. The various components of the venous system are depicted in Figure 3- 15. Thrombosis in any

""he,wp.,;,"" sinus

_ Pos'e,;o, intercavernous sinus -::::~:,~::~o:m~:e:~n; ; :n:;g:~.:a,'1 diploic vein \" vein ~~.ave"n homatropine>scopoiamine>cyclopentolate>tropicamide b. alropine>scopoiamine> homatropine>cydopentolate>tropicamid e c. cyclopentolate>tropicamide>scopolamine>homatro pine>atropine d. homatropin e>cyclopentolate>tropi cami de >scopolamine>atropine e. homatropine>atropine>scopolamine>cyciopentolate>tropicamide

45. Which of the follOWing agents are associated with co rneal complications, including melting and corneal perforations? a. topical alpha agonists b. topical steroids

c. topical carbonic anhydrase inh ibitors d. topical nonsteroidal anti -inflammato ry drugs

46. Which of the following is a potential side effect of tetracyclines? a. depressio n of prothrombin h. inhibiti on of bactericidal antibiotics c. decreased efficacy of oral contraceptives

d. all of th e above 47. Whi ch of the following is the only agent to have a significant effect on postsurgical en dophthalmitis? 3.

preope rative preparation of the eye with topical povidone-iodine

h. intracamera l vanco mycin c. intracameral aminoglycosides d. subconj unctiva l fluoroquinolo nes

Answers 1. c. The greater wing of the sphenoid is part of the lateral wall of the orbit.

2. d . Cra ni al nerve IV passes through the superior orbital fissure but not through the annulus of Zinno 3. c. The lateral rectu s. The superior, inferior. medial, and lateral recti muscl es all arise from the annulus of Zinno 4. b. The 4 recti muscle insertions form the spiral ofTillaux, with the medial rectus inserting closest to the limbus, at 5.5 mm, and the supe rior rectus most distal from the limbus, at 7.7mm. 5. d. None of the above. The inner and outer limiting membranes are not true membranes. 6. d. The adult human eye has a focusing power of approximately 60 diopters (60 D). The air- tear interface of the cornea is responsible for approximately 40 D, and the lens contributes approximately 20 D of power. 7. d. The neurosensory retina. The uveal tract is the main vascular compartment of the eye and consists of the iris. ciliary body, and choroid. 8. h. C ranial nerve IV exits from the dorsal midbrain. It also has the longest intracranial course of any cranial nerve, approximately 75 mm. 9. c. 40 mm. The intraorbital portion averages 25 mm in length; however, the total nerve also co nsists of intraocular, intracanalicular, and intracranial portions. 10. d. The mandibular division of cranial nerve V (V J) does not pass through the cavernous si nus. 11. d . Aneurysms at the junction of the posterior communi cating an d internal carotid arteries may affect CN III (oculomotor). 12. c. Surface ectoderm. One of the earliest events of embryogenesis is the determination of lens development. The underlying mesoderm signals a region of surface ec toder m to become the lens. The lens becomes apparent by 27 days' gestation. 13. c. Ciliary epithelium is derived from th e optic cup, which is an extension of th e forebrain. 14. c. Homeobox genes are found across the entire plant and animal kingdom. 15. d. The hereditary pattern in familial reti noblastoma is autosomal dominant. The other 3 conditions appear to be a result of a defect in mitochondrial genes. 16. c. Only about 10% of patients with hereditary retinoblastoma have a famil y history of the disease. The remaining 90% appear to have a new mutation in th eir germ cells. 17. d. The inheritance pattern of mitochondrial disease might superficially resemble that of an X-linked trait. Maternal transmission, however, differs from X-linked inheritance in that all the offspring of affected femal es (both daughters and sons) can inherit the trait but only daughters can pass it on. L8. c. More than 70 diffe rent mutations are known to cause retinitis pigmentosa. 19. h. A significant number of disorders associated with the eye or visual system involve mitochondri al deletions or mutations. Mitochondrial diseas e should be considered whenever the inheritance pattern of a trait suggests maternal transmission.

414

Answers. 415 20. d. Linkage is the major exception or modification to the law of independent assortment.

Nonallelic genes located reasonably close togeth er on the same chromoso me tend to be transmitted together more frequently th an by chance alone; thus. th ey are said to be linked. 21. c. Mitochondrial genes are important in th e prod ucti on of peptides, which are involved in

the mitochondrial respi ratory chain and ATP synthase. 22. a. A PAX6 mutation is associated with aniridia. 23. c. Goblet cells make the mucin layer and meibomian glands make the lipid laye r. Glands

of Krause and Wolfring produce the aqueous laye r. 24. a. IgA and IgG are found in th e tear film. 25. c. Descemet's membrane is a true basement membrane produced by th e corneal endothe-

lium. 26. d. Descemet's membrane is a IO-Ilm-thick basement membrane between the endothelium and posterior co rneal stroma. Type IV collage n is the most abundant collagen in Descemet's membrane. Type I collagen, however, is th e major collage n component of th e corn eal stroma. 27. h. The endothelial pump is responsible for ge nerating the negative hydrostatic pressure that is necessary for holding the LASIK flap in place after surgery. 28. d. E-Crystallin is a taxon -specific crystallin, which is found only in a phylogenetically restricted group of species. 29. c. Blue light is predominantly absorbed by co nes that absorb the shorter wavelengths (ie, 440 nm ).

30. a. Cone photoreceptor density is greatest in th e macular region of the retina. 31. a. Vitamin A, a metabolic precursor of ll -cis-retinaldehyde, is most necessary for the light-induced photoreceptor response. 32. b. Compared with younger patients, older pat ients have less lea n body mass due to a de-

crease in muscle bulk, less body water and albumin, and an increase in relative adipose tissue. These physiologic differences alter tissue binding and drug distribution. Human renal function decreases with age. HepatiC perfu sion and enzymatic activity are also affected by age. 33. h. Miotic agents co nstrict the pupillary sphincter and the ciliary muscle. Increasing myopia and decreased central anterior chamber are a result of ciliary muscle contraction. Pu pillary constriction causes decreased night vision but increases the range of accommodation (pinhole effect ). 34. a. In this list, pilocarpine (lsopto Carpine, Pilocar. Pilostat) is the onl y direct-acting cholinergic age nt. 35. c. Cocaine blocks re-uptake of norepineph rine at adrenergic receptor terminals. This increases the adrenergic response but does not directly stimulate or block receptor response. 36. d. Oral carbonic anhyd rase inhibitors can have many system ic side effects, one being a system ic metabolic acidosis, not alkalosis. 37. d. Ketorolac tromethamine (Acular) is a nonsteroidal anti-inflammatory age nt. Each of the others is a mast-cell stabilizer and an antihistamine, or they combine the effects of both.

416 • Answers

38. b. Amphotericin B is an antifungal agent. 39. c. Bupivacaine has the longest duration of effect (8-12 hours) of the locallregional agents listed. 40. c. The fourth cranial nerve (eN IV) is located outside the muscle cone in the orbit and is least likely to be affected by injection of retrobulbar anesthetics. 41. b. When a 50·~L drop is delivered from the usual commercial dispenser, the volume of the tear lake rises from 7 ~L to only 10 ~L in the blinking eye of an upright patient. Thus, changing the volume of the drop does not enhance the absorption of medication. 42. b. Studies of the permeability of isolated corneas to families of chemical compounds show that lipid solubility is more important than water solubility in promoting penetration. 43. d. A 0.5% solution has 0.5 gramllOO milliliters (mL), or 5 milligrams (mg)lmilliliter. As there are approximately 20 drops per milliliter, there are 5 mg120 drops. So, 5 mg120 drops ~ 0.25 mgll drop. If this drop is given bilaterally, there is up to 0.50 mg of active agent available for systemic absorption. 44. b. The duration of action of atropine is 7-14 days, scopolamine is 4-7 days, homatropine is 3 days, cyclopentolate is 2 days, and tropicamide is 4-6 hours. 45. d. Both diclofenac and ketorolac have been associated with corneal complications, including melting and perforation. The preponderance of patients were found to be on generic diclofenac, which was subsequently removed from the US market. 46. d. Tetracyclines may depress prothrombin, thus prolonging the bleeding in patients on anticoagulation medication. As bacteriostatic drugs, tetracyclines may inhibit bacterial medications and should not be used concurrently. They also may decrease the efficacy of oral contraceptives. 47. a. Topical povidone-iodine solution (Betadine 5%) exhibits broad-spectrum antimicro-

bial activity when used to prepare the surgical field and rinse the ocular surface. It has been shown to have a significant effect on postsurgical endophthalmitis.

Index (j = (lgurc; t = table) AA. See Arachidonic acid ABC transporters. See ATP binding cassette (ABC)

transporters Abducens nerve. See Cranial nerve VI Ahetalipoprole inem ia

microsomallriglyccride transfer protein defects causing. 298

vitamin supplements in management of, 232 AC(llI tIUlIIlOcba, 385 treat me nt of keratitis/ocular infection caused by.

385- 386 Acceptor splice site, 147

Accessory lac rimal glands, 26f. 27/, 33, 239-240, 239/ of Krause, Bf, 26f, 271, 33, 239-240 of Wolfring. 23/. 26f. 27/, 33, 240 Accommod ation, 67, 69j. 70 aging affecting, 67 muscarinic drugs affecting. 335 in near reflex. 99 Accommodative esotropia, m uscarinic agents for managem ent of, 339

Accbulola!' 345/ Acetazolamide, 351, 352t, 353 susta ined- release ora l preparation fo r, 329, 353 Acetylcholine, 2591 clin ical usc of, 335~33 7, 336/ drugs affec ting receptors for, 334 - 344, 335f. 336f. 337f. 339f. 343f Sec also Cholinergic agents in iris-ciliary body, 258, 2591 sphin cter activity affected by, 260 synthes is/ release/degradat ion of, 335- 337, 337j in tear sec retion, 240, 242, 242/ Acetylch olinesterase. See Cholinesterasel acetylcholinesterase Acetylcholineste rase inhibitors. Sec C holinesterasel acety lcholinesterase inhib itors Acetylcysteine, 333 Acetyltransferasc. in isoniazid pharmacogenet iCS. 229 Ach . Sec Acetylcholine Achromatopsia gene defects causing. 297 with myopia. racial an d e thnic concentration of, 21 1 Achromycin. See Tetracycl ines Acidic fibroblast growth fac to r. Sce aiso Fibroblast growth fac to r in aqueous humor, 270 Acidosis, carbonic anhydrase lOP lowering and. 353 Acinar cells, lacrimal gland, 32. 33/ differentiation of, 140 Acroce ntric chromosome, 147 ACTH (adrenocorticotropic hormone), in tear secretion, 244 Actin. 277 Actin fila ments. 277 Activase. Sce Tissue plasminogen activator Activators, 332

Active transport /secret ion ac ross retinal pigmen t epithelium. 307 aqueous humor composit ion affected by, 266 in aqueous humor d ynam icS, 254. 255 in lens, 278 Acular. See Ke torolac Acyclovir, 38 lf, 382-383 Adaptation, light, 294 Adenylyl/ adenylate cyclase adrenoceptor binding and, 348, 349 recepto r- effector coupling a nd, 262, 262/ tear secretion and, 243, 243/ Adie pupi l (tonic pu pil). pharmacologic test ing for, 338 Adnexa. See Ocular adnexa Ad renaline. See Ep inephrine AdrenergiC agents. 344- 35 1. 345f. 347f. 3471, 350f See

also specific agenr for glaucoma agoni sts, 2641, 346-347, 3471, 348- 349 antago nists /p-blockcrs, 264 !, 349- 35\, 3501 as miotics, 260, 348 modes of action of, 2641 as mrd riatics, 260, 345-346 systemic absorp tion of, 344 AdrenergiC n eurons, 259 AdrenergiC receptors, 259, 259! drugs affecting, 344-35 1, 345/ in iris- ciliary body, 259, 259!, 260, 262~263, 344 locations of, 344 signal transduction and , 262- 263, 262f. 263f, 264! in tear secretion, 242, 242f, 243, 243f Adrenocorticotropic h o rmo ne (ACTH), in tea r sec retion, 244 ADRP. See Retinitis p igmen tosa, autosomal dom inan t Advi1. See Ibu profen Afferent fibers somatic. 105 visceral, 105 Afferent pupillary pathway, 99 nFGF. See Acidic fibrobl ast growth fac tor Age/aging accommodative response/ presbyopia and, 68 ciliary muscle affected by, 63 Descemet's membra ne/ corneal e ndot h elium affected by. 45, 251 lens changes associated wi th . 67-68, 314 len s proteins affected by. 277 mitochondrial DNA diseases and. 173 parental, chromosomal aberrations in Down syndrome and, 20 1, 202 pha rmacologic principles aflected by. 323 vit reous changes associated with, 84, 84f, 286-289 Age- related cataracts, in d iabetes, 279 Age- Related Eye Disease Stud y (A REDS), 314~3 1 5 Age- related macula r d egene ration/ macu!opathy (sen ile macula r degeneration), retinal pigment epitheliu m abno r malities associated wit h , 309 Agonist, 33 1

417

418 • Index Aicardi syndrome, 220

Air-tear film interface. 43, 44/ AK Beta. See levobunolol AK -Chlor. See Chloramphenicol AK-Con. See Naphazoline AK-Dex. See Dexa methasone AK -Dilatc. See Phenylephrine AK-M)'d n. See Eryth romycin AK·PenlOlate. See Cydopentolate AK-Poly- Bac. See Polymyxin B. in combination

preparations AK-Pred. See Prednisolone

AK-Sulf. See Sulfacetamide AK-Tob. See Tobrnmycin AK-Tracin. See Baci tracin Akarpine. See Pilocarpine AKPro. See Dipivefrin Alamast. See Pemirolast Alaway. See Ketotifen Albalon. See Naphazolin e Albinism, 2 13t, 2 14, 308 defective melanin synthesis and, 308 enzyme defect in , 2 131 , 214 oc ular, 308

ocular findings in carriers of. 222J. 222t X-li nked (Nettleship-Falls), ocular findings in carriers of. 222j. 223 oculocutaneous, 195. 308 racial and ethn ic concentration of. 211 tyrosinase-negative/ positive. 195.2131,308 Albumin in aqueous h umor, 268 in vitreous, 285 Alburerol,2591 Akainc. See Proparacaine Alcohol (ethanol), use/abuse of, maternal, malfo rmat io ns associated \vith . 142- 143. 142/ Aldehyde dehydrogenase, in cornea, 248 Aldose reductase in cataract formation , 280-28\ in lens glucoselcarbohydrate metabolism, 280, 280/ Alkaptonuria, 2 12- 2 14, 2UI AJI-trmls-retinol/ all -tralls-retinaldehyde. 293. 306 Allele-specific marking (genetic imprinting). 154, 169 Allele-spedfic o ligon ucleotides. 148 in m utation screening, 184 Alleles, 148. 194 - 195 n uU. gene therapy and. 187- 188 Allelic association. See Linkage disequilibrium Allelic heterogeneity. 148, 192- 193, 193 Allergic conjunctivitis, drugs for. 364- 366, 365t Allergic reaction s. to penicillin. 369 Alocri!. See Nedocromil Alomide. See Lodoxamide Alpha (u )· adrene rgic agents, 345-348, 347f, 347t agonists, 347/ direct-acting, 345-346 for g laucoma. 264/. 346- 347 indirect-acting, 346- 348. 347/ antagonists, 260. 348 Alpha (a)· adrenergic receptors. 344, 345/ blocking, 260 in iris-ciliary body, 259. 2591. 260. 262- 263

signal transduction and. 262 - 263. 262j. 263J, 2641 in tear secretion, 242, 242/ Alpha l (oj)-antit rypsi n, in aqueous humor, 269 Alpha (a)- blockers, 260. 348 Alpha (a)-crystallins. 70. 276 Alpha (u)-galaClosidasc, defective, 2 131 Alpha (a) helix. 166, 167/ Alpha (u)- L - i duronid;l.~e, defective. 2 131 Alphal (ul l-macroglobulin , in aqut.'Ous humor, 269 Alpha (u)-m:mnosidase. defective, 2 13t Alpha «(1) -mehlllocyte-stim ulating hormone (u- MSH ). in tear secretion, 244 Alphagan. See I3rimonidine Alport d isease/syndro me. pleiotropism in , 2 10 Alrex. Sec Loteprednol Altacai ne. See Te tracaine Altafri n. See Phe n),lephrine Alternat ive splicing, 165, 168 Alu repeat sequence, 148, 166 Amacrine cells, 75f, 300 differentiation of, 126 Amau rosis Leber congeni tal (congenital/inrantile/ childhood retinitis pigmentosa) guanylate cyclase mutations causing. 296 RPE65 gene defects causing, 297 Amber codon , 148 Amethocaine. See Te tracaine Amikacin, 3681. 375- 376 Amino acids in aqueous hu mor. 255 140 in tear Aminoca proic acid/ c-aminocaproic acid. 394 Aminoglycos ides, 3721. 375- 376 ototoxicity of, m itochond ria l DNA mutations and, 173. 176 p-Aminohippuric acid , in aqueous h umor dynam ics, 255 Am niocentesis, 228- 229 Amoxicill in .370 Amphotericin H, 379- 380, 379t Ampicillin, 368/, 370 intravenous administration of, 329 Amplifying cells. transient, in corneal epithelium, 43 Anaerobic glycolYSiS. in glucose/carbohydrate me tabolism in cornea. 248 - 249 in lens. 278 Anaphase lag, mosaicism caused by, 203 Anaphylactoid reactions, penicillin causing, 369 Anaphylaxis, penicillin allergy caus ing, 369 Ancobon. Sec Flucytosine Androgens, in tear secretion, 244 Ane mia. aplastic carbonic anhydrase inhibitors caUSing, 354 chloramphenicol causing, 375 Anestacaine. Su Lidocaine Anesthesia (anestheticsl, local (topical/regio nal). 386- 390. 387t for anterior segment surgery, 389- 390 in patients taking cholinesterase inhibitors, 340 AneuplOidy. 148. See IIlso specific disorder of autosomcs, 199-203 of sex chromosomes. 199

mm,

Index . 4 19 Aneurysms, cranial nerve 111 affected by. 99 Angelman syndrome. imprin ting abnormalities causing. 154 , 169 Angiogenesis, vitreous as in hibitor of. 287 Angular artery eyelids supplied by, 29 orbit supplied by, 37/ Angu lar vein. 40j Aniridia. 205- 207 mutation rate of. 207 short arm I I deletion synd romelPAX6 gene mutations and, 141. 166.205.206.2 16 Annulusof Zinn , 10, 16f.1 7J. 18. 191.9 1 Anomalies. congenital. Sec specific lype and Congen ita l anom alies Antagonist, 332 Antazoline.364 Anla1.Oline/napnazoiine, 364, 3651 Anterior banded zone, of Desccmet's membrane, 45. 46[,25 1 Anlerior cerebral artery. 93 Anterior cha mber, 41 -42. 41J. SO- 52, 51/. 52/ depth of, 50 development of. 135- 136, 136/ topography of, 41 - 42, 41/ Anterior chamber angle, 41J. 49f. 50. 5 1f, 52/. 53j development of, 135- 136. 136j Ante rior ci liary arte ries. 2 1,34. 36- 38,38, 38j; 39f. 62. 64 development of. 132 Anterior cli noid process, Ilf Anterior communicating artery. 93 Anterior inferior cerebellar artery. 104 An terior lacrimal crest. 5, 6J. 27 An terior lamella, 25f Anterior pigmented layer, of id s. 58, 60f Anterior .~cg ment , surgery on , topical anesthetics for.

389-390 Ante rior uvei tis, corticosteroid route of administration in . 3601 Antibacterial agents. 368- 378. 3681. 3721. 3731. See elisa specific agenl (lnd Antibiotics Ant ibiotics. 368-378, 368(, 3721. 3731. Sec (lIsa specific

Iype aud specific agelll for ACClllllmmoeba keratitis, 385- 386 p-Iactam, 368- 371 , 3681 in ((l mbination preparat ions with ant i-in namm atory agents, 373t intrave nous administration 0(, 329 ototoxicity of, mitochond rial DNA mutations and. 176 resistance to. 369, 37 1,375.377 Anticholinergic agents. 260. 334. 340-342. 34 11,342 adverse effects of, 342. 343f Anlicipalion (genetic). 148. 162.208- 209 Ani idt·pressants. aprac\onidine/brimonidinc interaclions and, 348 Anlifibrinolytic agents, 394 Alltifibroti c agents, 366-368 Anti fungal agents, 378 - 380. 3791 An tigen -presenting cells. ill cornea, 43 Anliglaucoma agents ad renergic agonists u -adrenergic agonists. 264 (, 346-347 p-adrenergic agonists, 3471. 348-349

p-blockers, 2641, 349-351. 3501 calcium channel blockers. 261 carbonic anhydrase inhibitors. 255, 351-354, 3521 ci liary body as target fo r. 254 combined preparati ons. 355 cycloplegics, 34 1 hypc rosmotic!os rnotic ,lgcn ts, 355-356, 3561 hltanoprost, 354. 3541 miotics. 264(, 338 prostaglandin analogues. 256- 257, 2641. 354-355, 3541 receptors in mode of action of. 264 , 2641 Antihistamines. 364. 365t Anti-infective age nts, 368- 386. See also specific type and AntibiOlics Ant i-in nammatory agellts, 356- 368. 357r, 3601, 3621, 3651. See also specific agenl (HId Corticosteroids: No nsteroidal anti-int1a lllmatory drugs ar'lChidon ic acid release affec ted by, 358 in combination preparations wit h antibiotics, 3731 fo r keratoconjunctivitis sicca, 245 AntimetaboHtes, 366-368 Anlimuscari nic agents. 340-342, 341 1 adverse effects of, 342. 343/ Anliollcogenes. See Tumor-suppressor genes Antioxidants in lens, 313 - 314, 3 14f in retina and retina l pig mcnt epithelium, 315-3 16, 316- 318 supplemental, 395 Antisense DNA, 148 in gene therapy, 188. 189/ AntiSe nse oligonucleotides. in gene (he rap)'. 188, 189/ It ,-A nt itrypsin. in aqueous humo r, 269 Antiviral agents, 380-385, 38 1t fo r herpetic eye diseasc. 380, 38 11. 382-383 intravitreal admin istrati on 0(, 328 resistance to, 382 systemic. 38 1t, 382-385 topical. 380, 38 1f Aplastic anemia carbonic anhydrase inhibitors causing, 354 chloramphenicol causing. 375 Apocri ne glands of eyelid , 23. 271 Apolipoprotein D, in aqueous humor. 269 Aponeurosis, levator. See l.evator aponeurosis Apop\()sis, 147, 148 in DNA repair, 170 Appositional growth , in development of lamellae, 135 Aprac\onid ine, 259 /, 346, 3471 Aquaporin 0 (majo r intrinsic protei n/MIP). 274, 277 in lens transport, 277 Aqueous humor, SO, 254, 265- 272 biochemistry and metabolism of. 254- 255.165-272 carbohydrates in, 266/, 268 carbon dioxide in, 272 ca rbonic anhydrase inhibito rs su ppressing formation of, 35 1, 352 com position of, 265- 272. 266t dynamics of. 254- 255, 265 glutathione in, 268 growth mod ulator)' fac tors in, 270-27 1 inorganic ions in, 2661, 267 intraocular pressure and. 255. 265

420 • Index organic anions in, 2661, 267

ATPasc-6 gene, in neuropathy with ata.'( ia and retinitis

oxygen in. 27 1- 272

pigmentosa. 175 Atrial natriuretic peptide. in aqueous humor, 267 Atrophy, gyrate, 2131 ornithine aminotransferase defec ts causing. 2 131. 298 rel inal pigment epitheliu m in, 309 Atropine. 2591, 260. 340- 342. 34 11 adverse effects of. 3431 in Down syndrome patients. pharmacogenetics and. 229 systemic absorpt ion of. 324 Atropi ne-Care. See Atropine Atropisol. See Atropine Auditory meatus. internal, 105 Aulomated DNA seq uencing, 184, 185f Autonomic pathways. cholinergic drug action and, 334, 335/ Aulo-oxidation, 31 2- 3 13 in lens. 313. 3 14f vitamin E affecting, 3 12. 3 17 Autosomal dominant inheritance. 2 16-21 7, 217t Autosomal recessive inh eritance. 2 12- 216, 213/, 21 51 Autosomes, 148, 193 aneuploidy of, 199- 203. See also specific disorder Axenfc1 d anomaly/synd rome, 141 Axenfeld loop, 48 AzaSite. See Azit hromycin Azelastine, 364, 3651, 366 Azidothymidine. See Zidovud ine Azithromycin. 3721. 377 Azlocillin.370 Azapi. See Brinzolamide AZT (azidOlhymidine). See Z idovud ine

proteins in , 254, 255. 266. 268-270 separat ion of from blood . Sec Blood-aqueous bar rier sodium transport and, 351 urea in, 268 vascular endothelial growth fa cto r (VEGF) in, 270, 27 1 Aqueous layer (component ) of tear 42, 237, 238[ Aqueous tear deficiency, 244- 245 Aqueous veins, 54, 57! Arachidonic add (a rachidonate) in eicosanoid synt hesis. 255, 256f, 257 nonsteroidal allli -inflammatory drug derivation lind,

mm.

36 1-362 release of, 257 anti-inflammatory drugs affecti ng. 358 in re tinal pigment epithelium. 305 in vitreous, 286 Arachnoid mater, optic ne rve. 9 1. 92f. 93/ Area centralis. 79, SOj. See also Macula AREDS (Age-Related Eye Disease Study), 314-315 Arrestin, 293 mutations in, 182. 295 ARRP. See Retinit is pigmentosa. autosomal recessive Arterial circles, 38. 391, 571, 58 development of, 132, 138 Arteria l plexus, cili ary body, 62 Arteritis, giant cell (tempora]), corticosteroid route of administration in, 3601 Arlifkial tears, 245, 390- 39 1 Arylsulfatase A, defective. 2 131 Ascertainment. 148 Ascorbate. See Ascorbic acid Ascorbic acid (vitamin C) antioxidant effect of, 317- 3 18 in lens, 314- 3 15 in retina and retinal pigment epitheli um, 3 17-318 in aqueous humor, 255. 2661 oral supplements and. 3 14-3 15 in tea r film , 240 in vitreous. 2661 ASO. See Allele-specific oligonucleotides Aspirin. 362-363. 3621 prostaglandin syn thesis afrected by, 257 Association (genetic). 177 al lelic. See Linkage d isequi librium Assortalive mati ng. 148 Astrocytes optic ne rve, 90. 9 1, 921 retinal, 77, 30 I Ataxia interm ittent. 2131 with neuropathy and retinitis pigmentosa, 175- 176 mitochondrial DNA mutations and, 174[. 175 - 176 Ataxia-telangiectasia ( Louis- Bar syndrome). ATM mutat ion in, 170 Atenolol. 3451 ATM gene mutation . 170 ATP binding cassette (A BC) transporters, 293 mutations in, 296 ATP production in lens, 278-279 in rod outer segments, 293

SAC (bacte ria l artificial chromosome). 149 Sacampicillin, 370 Bacitracin, 3681. 3721, 378 in combination preparations. 3721, 3731 Bacterial artificial chromosome (BAC), 149 Bacteriophage. 149 HAL ( British anti lew isite), for Wilson disease, 231 Ha rdet-Hiedl syndrome, pleiOl ropism in , 2 10 Baroreceptors. phe nylephrine affec ting. 346 Barr body, 149 Basal lamina (basal cell layer) of choriocapillaris. 64, 651 ciliary body. 62. 621 corneal. 43, 44J. 45. 46J. 248. See also Descemet's membranellayer lens_ See Lens capsule of retinal blood vessels. 78 of retinal pigment e pithelium , 64. 651 Base pair. 149 mutations of, 17 1 conserved,17 1 Basic fibroblast growth factor, 270, 348. See also Fibroblast growth factor in aqueous humor. 270 Hasic secretion test/basic secretDrs. 241 Basilar arlery, 109 Bassen-Kornzweig s)'ndromc. MTP defects causing, 298 Balson venous plexus, 104 BAX gene, in DNA repair, 170

Index . 421 Beaded fila ments. 277 Bcnoxi nutc. with flu orescein , 387 1, 389 Bem.alkonium absorption affected by, 327 in art ificial tears, 39 1 toxic reactions to. 322 Bergmeister papilla. 85 Best disease (vitelli form macular dystrophy/ vitel liruptive macular dege neration ) bestrophin defect causing, 297 identification of carriers fo r, 217 retinal pigment epitheli urn in, 308- 309 Bestrophin, mutations in. 297 Beta (Il)-ad renergic agents, 3471. 348- 35 1, 350r ago nists. 3471, 348- 349 antago nists, 349- 35 1, 3501 for glaucoma. 264 /, 3471. 348- 349 Beta (Il)-adre nergic receptors, 2641. 344. 345J. 3471, 348- 349 in iris-ci liary body, 2591. 262, 263 signal transduction and. 262. 262J. 263. 264 1 in tear secret ion . 243, 243f Beta (P)-blockers, 349- 35 I , 350t for glaucoma, 264 1. 349- 35 I . 350t Beta (Il) carotene. antioxidant effect of. 3 15 oral supplements and . 3 15 Beta H!l-crystallins. 70, 276 Bela (p)-galactosidase, defective. 2131 Beta