AAO BCSC 2020-2021 Fundamentals and Principles of Ophthalmology PDF

2 Fundamentals and Principles of Ophthalmology Last major revision 2019–2020 2020–2021 BCSC Basic and Clinical Science Course™...

2 Fundamentals and Principles of Ophthalmology Last major revision 2019–2020 2020–2021 BCSC Basic and Clinical Science Course™ Published after collaborative review with the European Board of Ophthalmology subcommittee The American Academy of Ophthalmology is accredited by the Accreditation Council for Con tinuing Medical Education (ACCME) to provide continuing medical education for physicians. The American Academy of Ophthalmology designates this enduring material for a maximum of ™ 15 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. CME expiration date: June 1, 2022. AMA PRA Category 1 Credits tween June 1, 2019, and the expiration date. ™ may be claimed only once be ® BCSC volumes are designed to increase the physician’s ophthalmic knowledge through study and review. Users of this activity are encouraged to read the text and then answer the study questions provided at the back of the book. ™ To claim AMA PRA Category 1 Credits upon completion of this activity, learners must demon strate appropriate knowledge and participation in the activity by taking the posttest for Section 2 and achieving a score of 80% or higher. For further details, please see the instructions for requesting CME credit at the back of the book. The Academy provides this 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 physician’s own judgment or give specific advice for case management. Including all indications, contraindications, side effects, and alternative agents for each drug or treatment is beyond the scope of this material. All information and recommendations should be verified, prior to use, with current information included in the manufac turers’ 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 labeling, 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 status of each drug or device he or she wishes to use, and to use them with appropriate, informed patient consent in compliance with applicable law. The Academy specifically 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 recommendations or other information contained herein. All trademarks, trade names, logos, brand names, and service marks of the American Academy of Ophthalmology (AAO), whether registered or unregistered, are the property of AAO and are pro tected by US and international trademark laws. These trademarks include AAO; AAOE; AMERICAN ACADEMY OF OPHTHALMOLOGY; BASIC AND CLINICAL SCIENCE COURSE; BCSC; EYENET; EYEWIKI; FOCAL POINTS; FOCUS DESIGN (logo shown on cover); IRIS; ISRS; OKAP; ONE NETWORK; OPHTHALMOLOGY; OPHTHALMOLOGY GLAUCOMA; OPHTHALMOLOGY RETINA; PREFERRED PRACTICE PATTERN; PROTECTING SIGHT. EMPOWERING LIVES; and THE OPHTHALMIC NEWS & EDUCATION NETWORK. Cover image: From BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors. Photomicrograph depicting adenoid cystic carcinoma of the lacrimal gland. (Courtesy of Vivian Lee, MD.) Copyright © 2020 American Academy of Ophthalmology. All rights reserved. No part of this publication may be reproduced without written permission. Printed in China. Basic and Clinical Science Course Christopher J. Rapuano, MD, Philadelphia, Pennsylvania Senior Secretary for Clinical Education J. Timothy Stout, MD, PhD, MBA, Houston, Texas Secretary for Lifelong Learning and Assessment Colin A. McCannel, MD, Los Angeles, California BCSC Course Chair Section 2 Faculty for the Major Revision Vikram S. Brar, MD Robert L. Schultze, MD Chair Slingerlands, New York Richmond, Virginia Simon K. Law, MD Evan Silverstein, MD Los Angeles, California Richmond, Virginia Jennifer L. Lindsey, MD Ravi S. J. Singh, MD Nashville, Tennessee Shawnee Mission, Kansas David A. Mackey, MD Perth, Western Australia The Academy wishes to acknowledge the following committees for review of this edition: Committee on Aging: Elliot H. Sohn, MD, Iowa City, Iowa Vision Rehabilitation Committee: Mona A. Kaleem, MD, Ellicott City, Maryland Practicing Ophthalmologists Advisory Committee for Education: Bradley D. Fouraker, MD, Primary Reviewer and Chair, Tampa, Florida; Alice Bashinsky, MD, Asheville, North Car olina; David J. Browning, MD, PhD, Charlotte, North Carolina; Cynthia S. Chiu, MD, Oakland, California; Steven J. Grosser, MD, Golden Valley, Minnesota; Stephen R. Klapper, MD, Carmel, Indiana; Troy M. Tanji, MD, Waipahu, Hawaii; Michelle S. Ying, MD, MSPH, Ladson, South Carolina The Academy also wishes to acknowledge the following committee for assistance in devel oping Study Questions and Answers for this BCSC Section: Self-Assessment Committee: Deepa Abraham, MD, Seattle, Washington; William R. Barlow, MD, Salt Lake City, Utah; William L. Becker, MD, St Louis, Missouri; Michele M. Bloomer, MD, San Francisco, California; John J. Chen, MD, PhD, Rochester, Minne sota; Zelia M. Correa, MD, Baltimore, Maryland; Deborah M. Costakos, MD, Milwaukee, Wisconsin; Theodore Curtis, MD, Mount Kisco, New York; Laura C. Fine, MD, Boston, Massachusetts; Robert E. Fintelmann, MD, Phoenix, Arizona; Jeffrey M. Goshe, MD, Cleve land, Ohio; Mark Greiner, MD, Iowa City, Iowa; Paul B. Griggs, MD, Seattle, Washing ton; David R. Hardten, MD, Minnetonka, Minnesota; Rachel M. Huckfeldt, MD, Boston, Massachusetts; Sarah S. Khodadadeh, MD, Vero Beach, Florida; Douglas R. Lazzaro, MD, Brooklyn, New York; Amanda C. Maltry, MD, Minneapolis, Minnesota; Brian Privett, MD, Cedar Rapids, Iowa; Sunita Radhakrishnan, MD, San Mateo, California; Jordan J. Rixen, MD, Lincoln, Nebraska; Mark I. Salevitz, MD, Scottsdale, Arizona; Ravi S. J. Singh, MD, Shawnee Mission, Kansas; Mitchell B. Strominger, MD, Reno, Nevada; Janet Y. Tsui, MD, Santa Clara, California; Ari L. Weitzner, MD, New York, New York; Zoë R. Williams, MD, Rochester, New York; Kimberly M. Winges, MD, Portland, Oregon European Board of Ophthalmology: Peter J. Ringens, MD, PhD, EBO Chair for BCSC Section 2 and EBO-BCSC Program Liaison, Maastricht, Netherlands Financial Disclosures Academy staff members who contributed to the development of this product state that within the 12 months prior to their contributions to this CME activity and for the dura tion of development, they have had no financial interest in or other relationship with any entity discussed in this course that produces, markets, resells, or distributes ophthalmic health care goods or services consumed by or used in patients, or with any competing commercial product or service. The authors and reviewers state that within the 12 months prior to their contributions to this CME activity and for the duration of development, they have had the following financial relationships:* Dr Browning: Aerpio Therapeutics (S), Alcon Laboratories (S), Alimera Sciences (C), Emmes (S), Genentech (S), Novartis Pharmaceuticals (S), Ohr Pharmaceuticals (S), Pfizer (S), Regeneron Pharmaceuticals (S), Springer (P), Zeiss (O) Dr Correa: Castle Biosciences (C) Dr Fintelmann: Alphaeon (O), Strathspey Crown (O) Dr Fouraker: Addition Technology (C, L), Alcon Laboratories (C, L), OASIS Medical (C, L) Dr Goshe: Carl Zeiss Meditec (L) Dr Grosser: InjectSense (O), Ivantis (O) Dr Hardten: Allergan (C, L, S), Avedro (C), Eye Surgical Instruments (C, O), Johnson & Johnson (C), Oculus (L), Optical Systems Design (C, O), TLC Vision (C) Dr Huckfeldt: AGTC (S), MeiraGTx (S), Spark Therapeutics (S) Dr Klapper: AdOM Advanced Optical Technologies (O) Dr Privett: Omeros (O) Dr Radhakrishnan: Netra Systems (C, O) Dr Schultze: Alcon Laboratories (L), Bausch + Lomb Surgical (L), Novartis Alcon Phar maceuticals (L), Sun Pharmaceuticals (L) Dr Silverstein: I-See Vision Technology (O); Welch Allyn (C) Dr Sohn: GlaxoSmithKline (S), Oxford Biomedical (S), Regeneron (S), Sanofi Fovea (S) The other authors and reviewers state that within the past 12 months prior to their contri butions to this CME activity and for the duration of development, they have had no finan cial interest in or other relationship with any entity discussed in this course that produces, markets, resells, or distributes ophthalmic health care goods or services consumed by or used in patients, or with any competing commercial product or service. * C = consultant fee, paid advisory boards, or fees for attending a meeting; E = employed by or received a W2 from a commercial company; L = lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company; O = equity ownership/stock options in publicly or privately traded firms, excluding mutual funds; P = patents and/or royalties for intellectual property; S = grant support or other financial support to the investigator from all sources, including research support from government agencies, foundations, device manufacturers, and/or pharmaceutical companies Recent Past Faculty Michael H. Goldstein, MD Alon Kahana, MD, PhD William R. Katowitz, MD Lawrence M. Levine, MD In addition, the Academy gratefully acknowledges the contributions of numerous past faculty and advisory committee members who have played an important role in the devel opment of previous editions of the Basic and Clinical Science Course. American Academy of Ophthalmology Staff Dale E. Fajardo, EdD, MBA, Vice President, Education Beth Wilson, Director, Continuing Professional Development Ann McGuire, Acquisitions and Development Manager Stephanie Tanaka, Publications Manager Susan Malloy, Acquisitions Editor and Program Manager Teri Bell, Production Manager Jasmine Chen, Manager of E-Learning Beth Collins, Medical Editor Eric Gerdes, Interactive Designer Naomi Ruiz, Publications Specialist Debra Marchi, Permissions Assistant American Academy of Ophthalmology 655 Beach Street Box 7424 San Francisco, CA 94120-7424 Contents General Introduction........................ xvii Objectives............................ 1 PART I Anatomy......................... 3 1 Orbit and Ocular Adnexa.................. 5 Highlights............................. 5 Orbital Anatomy.......................... 5 Dimensions of the Adult Orbit................... 5 Bony Orbit........................... 6 Orbital Margin.......................... 7 Orbital Roof........................... 8 Medial Orbital Wall....................... 8 Orbital Floor.......................... 8 Lateral Orbital Wall....................... 10 Orbital Foramina, Ducts, Canals, and Fissures........... 10 Periorbital Sinuses....................... 12 Cranial Nerves........................... 15 Ciliary Ganglion.......................... 15 Branches of the Ciliary Ganglion.................. 15 Short Ciliary Nerves....................... 16 Extraocular Muscles......................... 17 Extraocular Muscle Origins.................... 18 Extraocular Muscle Insertions................... 20 Extraocular Muscle Distribution in the Orbit............ 20 Blood Supply to the Extraocular Muscles.............. 21 Innervation of the Extraocular Muscles............... 21 Fine Structure of the Extraocular Muscles.............. 22 Vascular Supply and Drainage of the Orbit............... 22 Posterior and Anterior Ciliary Arteries............... 22 Vortex Veins.......................... 22 Eyelids............................... 26 Anatomy............................ 26 Vascular Supply of the Eyelids.................. 37 Lymphatics of the Eyelids.................... 38 Lacrimal Glands and Excretory System................. 39 Lacrimal Gland......................... 39 Accessory Glands........................ 41 Lacrimal Excretory System.................... 42 vii viii  Contents Conjunctiva............................ 43 Caruncle............................ 44 Plica Semilunaris........................ 44 Tenon Capsule........................... 44 2 The Eye............................. 47 Highlights............................. 47 Introduction............................ 47 Topographic Features of the Globe................... 48 Precorneal Tear Film........................ 49 Cornea.............................. 50 Characteristics of the Central and Peripheral Cornea......... 51 Epithelium and Basal Lamina................... 51 Bowman Layer......................... 51 Stroma............................. 53 Descemet Membrane....................... 53 Endothelium.......................... 54 Limbus.............................. 55 Sclera............................... 56 Anterior Chamber.......................... 59 Trabecular Meshwork........................ 63 Uveal Trabecular Meshwork.................... 63 Corneoscleral Meshwork..................... 63 Juxtacanalicular Meshwork.................... 64 Schlemm Canal......................... 64 Collector Channels....................... 64 Uvea............................... 64 Iris................................ 68 Stroma............................. 68 Vessels and Nerves........................ 69 Dilator Muscle and Anterior Pigmented Epithelium......... 70 Sphincter Muscle........................ 71 Posterior Pigmented Epithelium.................. 71 Ciliary Body............................ 72 Ciliary Epithelium and Stroma.................. 72 Ciliary Muscle.......................... 75 Supraciliary Space........................ 76 Choroid.............................. 76 Choriocapillaris and Choroidal Vessels............... 76 Choroidal Stroma........................ 77 Lens................................ 79 Capsule............................ 79 Epithelium........................... 80 Fibers............................. 82 Zonular Fibers......................... 82 Retina............................... 83 Neurosensory Retina....................... 84 Topography of the Retina.................... 93 Contents d ix Retinal Pigment Epithelium..................... 97 Bruch Membrane.......................... 99 Ora Serrata............................. 99 Vitreous............................. 101 3 Cranial Nerves: Central and Peripheral Connections......................... 105 Highlights............................ 105 Olfactory Nerve (First Cranial Nerve)................ 105 Optic Nerve (Second Cranial Nerve)................. 109 Intraocular Region....................... 110 Intraorbital Region....................... 113 Intracanalicular Region..................... 115 Intracranial Region....................... 115 Visual Pathway......................... 115 Blood Supply of the Optic Nerve and Visual Pathway........ 119 Oculomotor Nerve (Third Cranial Nerve)............... 123 Pathways for the Pupil Ref lexes................. 126 Trochlear Nerve (Fourth Cranial Nerve)............... 127 Trigeminal Nerve (Fifth Cranial Nerve)................ 128 Mesencephalic Nucleus..................... 129 Main Sensory Nucleus..................... 129 Spinal Nucleus and Tract.................... 130 Motor Nucleus......................... 131 Intracranial Pathway of Cranial Nerve V............. 131 Divisions of Cranial Nerve V.................. 131 Abducens Nerve (Sixth Cranial Nerve)................ 133 Facial Nerve (Seventh Cranial Nerve)................. 133 Tear Ref lex Pathway...................... 135 The Cerebral Vascular System.................... 135 Cavernous Sinus........................ 135 Other Venous Sinuses...................... 136 Circle of Willis......................... 138 PART II Embryology...................... 141 4 Ocular Development.................... 143 Highlights............................ 143 General Principles......................... 143 Eye Development......................... 148 Lens............................. 153 Posterior Segment....................... 155 Uvea............................. 157 Cornea, Anterior Chamber, and Sclera.............. 161 Development of the Extraocular Muscles, Adnexa, and Orbit...... 162 Extraocular Muscles...................... 162 Adnexa............................ 163 Orbit............................. 164 x  Contents Genetic Cascades and Morphogenic Gradients............. 164 Homeobox Gene Program.................... 164 Growth Factors, Diffusible Ligands, and Morphogens........ 165 Future Directions....................... 166 PART III Genetics....................... 169 Introduction......................... 171 Terminology........................... 171 5 Molecular Genetics..................... 173 Highlights............................ 173 The Cell Cycle........................... 173 Meiosis............................ 174 Cell Cycle Regulation...................... 175 Gene Structure.......................... 176 Noncoding DNA......................... 177 Gene Transcription and Translation: The Central Dogma of Genetics... 178 Intron Excision........................ 179 Alternative Splicing and Isoforms................. 179 Methylation.......................... 180 X-Inactivation......................... 180 Imprinting.......................... 180 DNA Damage and Repair...................... 181 Repair............................ 181 Apoptosis........................... 182 Mutations and Disease....................... 182 Mutations Versus Polymorphisms................ 182 Cancer Genes......................... 183 Mitochondrial Disease....................... 184 Chronic Progressive External Ophthalmoplegia.......... 185 MELAS and MIDD....................... 185 Leber Hereditary Optic Neuropathy............... 185 Neuropathy, Ataxia, and Retinitis Pigmentosa........... 186 The Search for Genes in Specific Diseases............... 186 Polymerase Chain Reaction................... 186 Genetic Markers........................ 187 Gene Dosage......................... 187 Linkage and Disease Association................. 187 Candidate Gene Approaches................... 188 Mutation Screening........................ 189 Direct Sequencing....................... 189 Genome-Wide Association Studies................ 189 Determining Whether Genetic Change Is a Pathogenic Mutation... 194 Gene Therapy........................... 194 Replacement of Absent Gene Product in X-Linked and Recessive Diseases.......................... 194 Strategies for Dominant Diseases................. 197 Contents d xi 6 Clinical Genetics....................... 199 Highlights............................ 199 Introduction........................... 199 Pedigree Analysis......................... 200 Patterns of Inheritance....................... 202 Dominant Versus Recessive Inheritance.............. 202 Autosomal Recessive Inheritance................. 203 Autosomal Dominant Inheritance................ 206 X-Linked Inheritance...................... 208 Maternal Inheritance...................... 210 Terminology: Hereditary, Genetic, Familial, Congenital......... 210 Genes and Chromosomes...................... 213 Alleles............................ 214 Mitosis............................ 215 Meiosis............................ 215 Segregation.......................... 215 Independent Assortment.................... 216 Linkage............................ 217 Mutations............................ 217 Polymorphisms........................ 218 Genome, Genotype, Phenotype................. 218 Single-Gene Disorders..................... 218 Anticipation.......................... 218 Penetrance.......................... 219 Expressivity.......................... 220 Pleiotropism.......................... 220 Chromosome Analysis....................... 221 Indications for and Types of Chromosome Analysis......... 221 Aneuploidy of Autosomes.................... 222 Mosaicism.......................... 224 Important Chromosomal Aberrations in Ophthalmology...... 225 Knudson’s 2-Hit Hypothesis and the Genetics of Retinoblastoma and the Phakomatoses.................... 227 Racial and Ethnic Concentration of Genetic Disorders......... 229 Lyonization............................ 230 Complex Genetic Disease: Polygenic and Multifactorial Inheritance........................... 232 Pharmacogenetics......................... 233 Clinical Management of Genetic Disease............... 234 Accurate Diagnosis....................... 234 Complete Explanation of the Disease............... 234 Treatment of the Disease Process................. 235 Genetic Counseling........................ 236 Issues in Genetic Counseling.................. 237 Reproductive Issues...................... 238 Referral to Providers of Support for Persons With Disabilities.... 240 Recommendations for Genetic Testing of Inherited Eye Disease... 240 xii  Contents PART IV Biochemistry and Metabolism......... 243 Introduction......................... 245 7 Tear Film............................ 247 Highlights............................ 247 Overview............................. 247 Lipid Layer............................ 249 Mucoaqueous Layer........................ 251 Aqueous Component...................... 251 Mucin Component....................... 253 Tear Secretion........................... 253 Tear Dysfunction......................... 256 8 Cornea............................ 259 Highlights............................ 259 Biochemistry and Physiology of the Cornea.............. 259 Epithelium............................ 260 Penetration of the Corneal Epithelium.............. 262 Bowman Layer.......................... 262 Stroma.............................. 263 Descemet Membrane and Endothelium................ 266 Descemet Membrane...................... 266 Endothelium......................... 266 9 Aqueous Humor, Iris, and Ciliary Body.......... 269 Highlights............................ 269 Physiology of the Iris and Ciliary Body................ 269 Dynamics of the Aqueous Humor.................. 270 Blood–Aqueous Barrier..................... 270 Aqueous Humor Formation and Secretion............. 270 Composition of the Aqueous Humor................. 273 Inorganic Ions......................... 274 Organic Anions........................ 274 Carbohydrates......................... 274 Glutathione and Urea...................... 275 Proteins............................ 275 Growth-Modulatory Factors................... 277 Oxygen and Carbon Dioxide................... 278 Clinical Implications of Breakdown of the Blood–Aqueous Barrier.... 279 10 Lens............................... 281 Highlights............................ 281 Overview............................. 281 Structure of the Lens........................ 281 Capsule............................ 281 Epithelium.......................... 282 Cortex and Nucleus...................... 283 Contents d xiii Chemical Composition of the Lens.................. 284 Plasma Membranes....................... 284 Lens Proteins......................... 284 Transparency and Physiologic Aspects of the Lens........... 286 Lens Transparency....................... 286 Lens Physiology........................ 286 Lens Metabolism and Formation of Sugar Cataracts.......... 289 Energy Production....................... 289 Carbohydrate Cataracts..................... 289 11 Vitreous............................ 293 Highlights............................ 293 Overview............................. 293 Composition........................... 294 Collagen........................... 294 Hyaluronan and Chondroitin Sulfate............... 297 Soluble and Collagen Fiber–Associated Proteins.......... 298 Zonular Fibers......................... 298 Low-Molecular-Weight Solutes.................. 298 Hyalocytes.......................... 299 Biochemical Changes With Aging and Disease............. 300 Vitreous Liquefaction and Posterior Vitreous Detachment...... 300 Myopia............................ 301 Vitreous as an Inhibitor of Angiogenesis.............. 301 Physiologic Changes After Vitrectomy.............. 302 Injury With Hemorrhage and Inflammation............ 302 Genetic Disease Involving the Vitreous.............. 302 Enzymatic Vitreolysis....................... 304 12 Retina............................. 305 Highlights............................ 305 Overview............................. 305 Photoreceptors and Phototransduction................ 306 Rod Phototransduction..................... 306 Energy Metabolism of Photoreceptor Outer Segments........ 311 Cone Phototransduction.................... 311 Photoreceptor Gene Defects Causing Retinal Degeneration..... 312 Classes of Retinal Cells....................... 315 Neurons........................... 315 Glial Cells........................... 317 Vascular Cells......................... 317 Retinal Electrophysiology...................... 318 13 Retinal Pigment Epithelium................ 321 Highlights............................ 321 Overview of RPE Structure..................... 321 Biochemical Composition..................... 323 xiv  Contents Proteins............................ 323 Lipids............................ 324 Nucleic Acids......................... 324 Major Physiologic Roles of the RPE................. 324 Vitamin A Regeneration.................... 326 Phagocytosis of Shed Photoreceptor Outer-Segment Discs...... 328 Transport........................... 328 Pigmentation......................... 331 Retinal Adhesion........................ 331 Secretion........................... 332 The Role of Autophagy in the RPE.................. 332 The RPE in Disease........................ 332 14 Reactive Oxygen Species and Antioxidants........ 335 Highlights............................ 335 Overview............................. 335 Reactive Oxygen Species...................... 336 Sources of Reactive Oxygen Species................ 336 Lipid Peroxidation......................... 337 Reactive Oxygen Species and Defense Mechanisms........... 338 Oxidative Damage to the Lens and Protective Mechanisms....... 339 Vulnerability of the Retina to Reactive Oxygen Species......... 340 Antioxidants in the Retina and Retinal Pigment Epithelium....... 341 Selenium, Glutathione, and Glutathione Peroxidase......... 341 Vitamin E........................... 342 Superoxide Dismutase and Catalase................ 342 Ascorbate........................... 342 Carotenoids.......................... 343 The Role of Oxidative Stress in Vision-Threatening Ophthalmic Diseases...................... 343 Glaucoma........................... 345 Diabetic Retinopathy...................... 345 Age-Related Macular Degeneration................ 346 PART V Ocular Pharmacology............... 347 15 Pharmacologic Principles.................. 349 Highlights............................ 349 Introduction to Pharmacologic Principles............... 350 Pharmacokinetics....................... 350 Pharmacodynamics...................... 350 Pharmacotherapeutics..................... 350 Toxicity............................ 350 Pharmacologic Principles and Elderly Patients........... 351 Pharmacokinetics: The Route of Drug Delivery............ 352 Topical Administration: Eyedrops 352 Topical Administration: Ointments................ 358 Contents d xv Local Administration...................... 359 Systemic Administration.................... 361 Ocular Drug Design and Methods of Delivery............. 363 Prodrugs........................... 363 Sustained-Release Delivery................... 363 Collagen Corneal Shields.................... 365 New Technologies in Drug Delivery............... 365 Pharmacodynamics: The Mechanism of Drug Action.......... 367 Pharmacogenetics: The Influence of Genetic Variation on Drug Efficacy and Toxicity....................... 368 16 Ocular Pharmacotherapeutics............... 369 Highlights............................ 369 Legal Aspects of Medical Therapy.................. 370 Compounded Pharmaceuticals................... 372 Compliance............................ 373 Cholinergic Drugs......................... 374 Muscarinic Drugs....................... 375 Nicotinic Drugs........................ 381 Adrenergic Drugs......................... 382 a-Adrenergic Drugs...................... 384 b-Adrenergic Drugs...................... 387 Carbonic Anhydrase Inhibitors................... 391 Prostaglandin Analogues...................... 393 Nitric Oxide Donors........................ 394 Rho Kinase Inhibitors....................... 395 Fixed-Combination Medications................... 397 Osmotic Drugs.......................... 397 Actions and Uses........................ 397 Intravenous Drugs....................... 398 Oral Drugs.......................... 398 Anti-inflammatory Drugs...................... 399 Glucocorticoids........................ 399 Nonsteroidal Anti-inflammatory Drugs.............. 407 Antiallergic Drugs: Mast-Cell Stabilizers and Antihistamines..... 411 Antifibrotic Drugs....................... 413 Medications for Dry Eye...................... 415 Ocular Decongestants....................... 416 Antimicrobial Drugs........................ 417 Penicillins and Cephalosporins.................. 417 Other Antibacterial Drugs.................... 420 Antifungal Drugs....................... 429 Antiviral Drugs........................ 431 Medications for Acanthamoeba Infections............. 437 Local Anesthetics......................... 437 Overview........................... 437 Specific Drugs......................... 440 Anesthetics in Intraocular Surgery................ 441 xvi  Contents Purified Neurotoxin Complex.................... 443 Hyperosmolar Drugs........................ 443 Irrigating Solutions........................ 443 Diagnostic Agents......................... 444 Ophthalmic Viscosurgical Devices.................. 445 Fibrinolytic Agents......................... 445 Thrombin............................ 446 Antifibrinolytic Agents....................... 446 Vitamin Supplements and Antioxidants................ 447 Interferon............................. 447 Growth Factors.......................... 448 PART VI Imaging........................ 451 17 Principles of Radiology for the Comprehensive Ophthalmologist....................... 453 Highlights............................ 453 Overview............................. 453 Computed Tomography...................... 454 Disadvantages......................... 456 Magnetic Resonance Imaging.................... 457 Disadvantages......................... 458 Ultrasonography.......................... 462 A-Scan............................ 463 B-Scan............................ 464 Ultrasound Biomicroscopy................... 468 Ordering Imaging Studies...................... 472 Appendix: Genetics Glossary.................... 477 Basic Texts............................ 493 Related Academy Materials..................... 495 Requesting Continuing Medical Education Credit........... 497 Study Questions.......................... 499 Answer Sheet for Section 2 Study Questions.............. 507 Answers............................. 509 Index.............................. 517 General Introduction The Basic and Clinical Science Course (BCSC) is designed to meet the needs of residents and practitioners for a comprehensive yet concise curriculum of the field of ophthalmol ogy. 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 revises the course annually, with the goals of integrating the basic science and clinical practice of ophthalmology and of keeping ophthalmologists cur rent with new developments in the various subspecialties. The BCSC incorporates the effort and expertise of more than 90 ophthalmologists, organized into 13 Section faculties, working with Academy editorial staff. In addition, the course continues to benefit from many lasting contributions made by the faculties of previous editions. Members of the Academy Practicing Ophthalmologists Advisory Com mittee for Education, Committee on Aging, and Vision Rehabilitation Committee review every volume before major revisions. Members of the European Board of Ophthalmology, organized into Section faculties, also review each volume before major revisions, focusing primarily on differences between American and European ophthalmology practice. Organization of the Course The Basic and Clinical Science Course comprises 13 volumes, incorporating fundamental ophthalmic knowledge, subspecialty areas, and special topics: 1 Update on General Medicine 2 Fundamentals and Principles of Ophthalmology 3 Clinical Optics 4 Ophthalmic Pathology and Intraocular Tumors 5 Neuro-Ophthalmology 6 Pediatric Ophthalmology and Strabismus 7 Oculofacial Plastic and Orbital Surgery 8 External Disease and Cornea 9 Uveitis and Ocular Inflammation 10 Glaucoma 11 Lens and Cataract 12 Retina and Vitreous 13 Refractive Surgery References Readers who wish 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. These references are intended to be selective rather than exhaustive, chosen by the BCSC faculty as being important, current, and readily available to residents and practitioners. xvii xviii  General Introduction Multimedia This edition of Section 2, Fundamentals and Principles of Ophthalmology, includes videos related to topics covered in the book. The videos w ere selected by members of the BCSC faculty to present important topics that are best delivered visually. This edition also in cludes an interactive feature, or “activities,” developed by members of the BCSC faculty. Both the videos and the activities are available to readers of the print and electronic versions of Section 2 (www.aao.org/bcscvideo_section02) and (www.aao.org/bcscactivity _section02). Mobile device users can scan the QR codes below (a QR-code reader must already be installed on the device) to access the videos and activities. Videos Activities Self-Assessment and CME Credit Each volume of the BCSC is designed as an independent study activity for ophthalmology residents and practitioners. The learning objectives for this volume are given on pages 1 and 2. The text, illustrations, and references provide the information necessary to achieve the objectives; the study questions allow readers to test their understanding of the mate rial and their mastery of the objectives. Physicians who wish to claim CME credit for this educational activity may do so online by following the instructions at the end of the book. This Section of the BCSC has been approved as a Maintenance of Certification (MOC) Part II self-assessment CME activity. Conclusion The Basic and Clinical Science Course has expanded greatly over the years, with the ad dition of much new text, numerous illustrations, and video content. Recent editions have sought to place greater emphasis on clinical applicability while maintaining a solid foun dation in basic science. As with any educational program, it reflects the experience of its authors. As its faculties change and medicine progresses, new viewpoints emerge on controversial subjects and techniques. Not all alternate approaches can be included in this series; as with any educational endeavor, the learner should seek additional sources, including Academy Preferred Practice Pattern Guidelines. The BCSC faculty and staff continually strive to improve the educational usefulness of the course; you, the reader, can contribute to this ongoing process. If you have any sug gestions or questions about the series, please do not hesitate to contact the faculty or the editors. The authors, editors, and reviewers hope that your study of the BCSC will be of last ing value and that each Section will serve as a practical resource for quality patient care. Objectives Upon completion of BCSC Section 2, Fundamentals and Principles of Ophthalmology, the reader should be able to identify the bones making up the orbital walls and the orbital foramina identify the origin and pathways of cranial nerves I–VII identify the origins and insertions of the extraocular muscles describe the distribution of the arterial and venous circulations of the orbit and optic nerve describe the anastomoses in the orbit between the external and internal carotid arteries describe the venous drainage of the eyelids and orbit, as well as the cavernous sinus describe the structural–functional relationships of the outflow pathways for aqueous humor of the eye identify various ocular tissues and describe their function and ultrastructural details describe the elements of the visual cycle and phototransduction cascade and their relation to vision and inherited retinal diseases state the events of embryogenesis that are important for the subsequent development of the eye and orbit identify the roles of growth factors, homeobox genes, and neural crest cells in the genesis of the eye describe the sequence of events in the differentiation of the ocular tissues during embryonic and fetal development of the eye draw a pedigree and identify the main patterns of inheritance describe the organization of the human genome and the role of genetic mutations in health and disease explain how appropriate diagnosis and management of genetic diseases can lead to better patient care describe the role of the ophthalmologist in the provision of genetic counseling as well as the indications for ordering genetic testing and referring patients for gene therapy discuss the biochemical composition of the various parts of the eye and the eye’s secretions list the various functions of the retinal pigment epithelium, such as phagocytosis, vitamin A metabolism, and maintenance of retinal adhesion describe the role of free radicals and antioxidants in the eye describe the phases of clinical trials in relation to drug approval by the US Food and Drug Administration describe the features of the eye that facilitate or impede drug delivery describe the basic principles of ocular pharmacokinetics, pharmacodynamics, and pharmacogenetics describe the basic principles underlying the use of autonomic therapeutic agents in a variety of ocular conditions list the indications, contraindications, mechanisms of action, and adverse effects of various drugs used in the management of glaucoma describe the mechanisms of action of antibiotic, antiviral, and antifungal medications describe the mechanisms of action, delivery, and side effects of drugs used in corticosteroid and immunomodulatory therapy describe available anti–vascular endothelial growth factor agents describe the anesthetic agents used in ophthalmology and methods of their delivery describe the basic principles of and indications for neuroimaging and ophthalmic ultrasonography as they relate to common ophthalmic and neuro-ophthalmic conditions PART I Anatomy CHAPTER 1 Orbit and Ocular Adnexa This chapter includes a related activity, which can be accessed by scanning the QR code provided in the text or going to www.aao.org/bcscactivity_section02. Highlights The shortest, most direct path to the optic nerve is along the medial wall. Emissary channels in the medial wall of the orbit can facilitate the spread of infec- tion from the ethmoid sinus into the orbit. The lesser wing of the sphenoid bone houses the optic canal. Fractures of the orbital floor can involve the infraorbital groove, which contains the infraorbital nerve, and should be suspected in cases of orbital trauma associated with infraorbital hypoesthesia. An imaginary line drawn externally between the extraocular muscle insertions ap- proximates the ora serrata internally. At the annulus of Zinn, the medial and superior rectus muscles are adjacent to the optic nerve sheath. Because of this anatomical relationship, patients with retrobul- bar optic neuritis experience pain with eye movement. The eyelid vasculature includes multiple sites of anastomoses between the external and internal carotid arteries. Orbital Anatomy Orbital anatomy, pathology, and changes associated with aging are discussed in detail in BCSC Section 7, Oculofacial Plastic and Orbital Surgery. Dimensions of the Adult Orbit Each eye lies within a bony orbit, the volume of which is slightly less than 30 mL. Each orbit is pear shaped; the optic nerve represents the stem. The orbital entrance averages approximately 35 mm in height and 45 mm in width and is widest approximately 1 cm behind the anterior orbital margin. The depth of the orbit, measured from the orbital en- trance to the orbital apex, varies from 40 to 45 mm, depending on w hether the measure ment is made along the lateral wall or the medial wall. Race and sex affect each of t hese measurements. 5 6 Fundamentals and Principles of Ophthalmology Bony Orbit The bony orbit surrounds the globe and helps protect it from blunt injury. Seven bones make up the bony orbit (Fig 1-1; also see Chapter 1 in BCSC Section 7, Oculofacial Plastic and Orbital Surgery): frontal bone zygomatic bone maxillary bone ethmoid bone Frontal bone Frontoethmoidal suture Posterior ethmoidal Anterior ethmoidal foramen foramen Optic canal Ethmoid bone Lesser wing of sphenoid bone Lacrimal sac fossa Superior orbital fissue Anterior lacrimal crest Optic strut Lacrimal bone Palatine bone Posterior lacrimal crest Greater wing of sphenoid bone Infraorbital groove Maxillary bone Inferior orbital fissure Zygomatic bone A Frontal bone Lesser wing of sphenoid bone Superior orbital Optic canal fissure Greater wing of Ethmoid bone sphenoid bone Lacrimal bone Zygomatic bone Lacrimal sac fossa Inferior orbital fissure Maxillary bone Infraorbital B groove Figure 1-1 A, Anatomy of the left orbit in a h uman skull. B, Color diagram of bones of the right orbit. The infraorbital groove leads to the anterior infraorbital canal and houses the infraorbital nerve. (Part A courtesy of Alon Kahana, MD, PhD; part B illustration by Dave Peace.) Chapter 1: Orbit and Ocular Adnexa 7 sphenoid bone (greater and lesser wings) lacrimal bone palatine bone Orbital Margin The orbital margin, or rim, forms a quadrilateral spiral whose superior margin is formed by the frontal bone, which is interrupted medially by the supraorbital notch (Fig 1-2). The medial margin is formed above by the frontal bone and below by the posterior lacrimal crest of the lacrimal bone and the anterior lacrimal crest of the maxillary bone. The infe- rior margin derives from the maxillary and zygomatic bones. Laterally, the zygomatic and frontal bones complete the rim. Supraorbital foramen/notch Frontal bone Trochlear fossa Frontozygomatic suture Lacrimal gland Zygomatic bone fossa Greater wing of sphenoid bone Lesser wing of sphenoid bone Figure 1-2 Right orbital roof. The orbital roof is composed of 2 bones: (1) the orbital plate of the frontal bone; and (2) the lesser wing of the sphenoid bone. The frontal sinus lies within the anterior orbital roof. The supraorbital foramen/notch, located within the medial one-third of the superior orbital rim, transmits the supraorbital nerve, a terminal branch of the frontal nerve of the ophthalmic division of cranial nerve V (CN V1). Medially, the frontal bone forms the roof of the ethmoid sinus and extends to the cribriform plate. (Illustration by Dave Peace.) 8 Fundamentals and Principles of Ophthalmology Orbital Roof The orbital roof is formed from 2 bones (see Fig 1-2): orbital plate of the frontal bone lesser wing of the sphenoid bone The fossa for the lacrimal gland, lying anterolaterally behind the zygomatic process of the frontal bone, resides within the orbital roof. Medially, the trochlear fossa is located on the frontal bone approximately 4–5 mm from the orbital margin and is the site of the pulley of the superior oblique muscle, where the trochlea, a curved plate of hyaline cartilage, is attached. Medial Orbital Wall The medial wall of the orbit is formed from 4 bones (Fig 1-3): frontal process of the maxillary bone lacrimal bone orbital plate of the ethmoid bone lesser wing of the sphenoid bone The ethmoid bone makes up the largest portion of the medial wall. The fossa for the lac- rimal sac is formed by the frontal process of the maxillary bone and the lacrimal bone. Below, the fossa is continuous with the bony nasolacrimal canal, which extends into the inferior meatus (the space beneath the inferior turbinate) of the nose. The orbital plate of the ethmoid bone, which forms part of the medial orbital wall, is a paper-thin structure—hence its name, lamina papyracea—and is the most common site of fracture following blunt trauma to the orbit. The medial wall has 2 foramina, which can act as conduits for processes involving the ethmoid sinus to enter the orbit. CLINICAL PEARL The most direct path to the optic nerve is along the medial wall: this is relevant for surgical procedures such as enucleation or optic nerve sheath decompression. Orbital Floor The floor of the orbit, which is the roof of the maxillary antrum (or sinus), is composed of 3 bones (Fig 1-4): orbital plate of the maxillary bone palatine bone orbital plate of the zygomatic bone The infraorbital groove traverses the floor and descends anteriorly into the infraor- bital canal. Both the groove and the canal h ouse the infraorbital nerve (maxillary division of the trigeminal nerve, V2), which emerges at the infraorbital foramen, below the orbital ChaPter 1: Orbit and Ocular adnexa 9 Frontal bone Frontoethmoidal suture Ethmoid bone Lacrimal bone Optic canal Post. lacrimal crest Ant. and post. ethmoidal foramina Ant. lacrimal crest Lacrimal sac fossa Lesser wing of Maxilloethmoidal sphenoid bone suture Maxillary bone Palatine bone Maxillary sinus Figure 1-3 Right medial orbital wall. The medial orbital wall is formed by 4 bones: (1) maxillary (frontal process); (2) lacrimal; (3) lesser wing of the sphenoid bone; and (4) orbital plate of the ethmoid. The largest component of the medial wall is the lamina papyracea of the ethmoid bone. Superiorly, the anterior and posterior foramina at the level of the frontoethmoidal suture trans- mit the anterior and posterior ethmoidal arteries, respectively. The anterior medial orbital wall includes the fossa for the lacrimal sac, which is formed by both the maxillary and lacrimal bones. The lacrimal bone is divided by the posterior lacrimal crest. The anterior part of the lacrimal sac fossa is formed by the anterior lacrimal crest of the maxillary bone. (Illustration by Dave Peace.) Nasolacrimal duct Figure 1-4 Right orbital floor. The orbital Infraorbital foramen floor is composed of 3 bones: (1) maxil- Zygomatic bone Lacrimal lary bone; (2) orbital plate of zygomatic Maxillary bone bone bone; and (3) palatine bone. The naso- (orbital plate) lacrimal duct sits in the anterior middle Infraorbital groove area of the orbital floor, medial to the Inferior orbital fissure Ethmoid origin of the inferior oblique muscle. bone (Illustration by Dave Peace.) Greater wing of sphenoid bone Palatine bone margin of the maxillary bone. For this reason, patients evaluated for orbital floor fractures should also be assessed for infraorbital hypoesthesia. Arising from the floor of the orbit just lateral to the opening of the nasolacrimal canal is the inferior oblique muscle, the only extraocular muscle that does not originate from the orbital apex. The floor of the orbit slopes downward approximately 20° from poste- rior to anterior. Before puberty, the orbital floor bones are immature and more prone to “trapdoor”-type fractures and secondary muscle entrapment. Wei LA, Durairaj VD. Pediatric orbital floor fractures. J AAPOS. 2011;15(2):173–180. 10 Fundamentals and Principles of Ophthalmology Frontosphenoid suture Greater wing of Frontal bone sphenoid bone Anterior clinoid Frontozygomatic process suture Zygomatic bone Superior Inferior orbital fissure orbital fissure Maxillary bone Palatine bone Maxillary sinus Figure 1-5 Right lateral orbital wall. The lateral orbital wall is formed by the zygomatic bone and the greater wing of the sphenoid bone. The junction between the lateral orbital wall and the roof is represented by the frontosphenoid suture. Posteriorly, the wall is bordered by the inferior and superior orbital fissures. The sphenoid wing makes up the posterior portion of the lateral wall and separates the orbit from the m iddle cranial fossa. Medially, the lateral orbital wall ends at the inferior and superior orbital f issures. (Illustration by Dave Peace.) Lateral Orbital Wall The thickest and strongest of the orbital walls, the lateral wall is formed from 2 bones (Fig 1-5): zygomatic bone greater wing of the sphenoid bone The lateral orbital tubercle (Whitnall tubercle), a small elevation of the orbital margin of the zygomatic bone, lies approximately 11 mm below the frontozygomatic suture. This important landmark is the site of attachment for the following structures: check ligament of the lateral rectus muscle suspensory ligament of the eyeball (Lockwood suspensory ligament) lateral canthal tendon lateral horn of the levator aponeurosis Orbital Foramina, Ducts, Canals, and Fissures Foramina The optic foramen is the entry point to the optic canal, which leads from the middle cra- nial fossa to the apex of the orbit (see Fig 1-1). The optic canal is directed forward, later- ally, and somewhat downward and conducts the optic nerve, the ophthalmic artery, and sympathetic fibers from the carotid plexus. The optic canal passes through the lesser wing of the sphenoid bone. The supraorbital foramen (which, in some individuals, is a notch instead of a fora- men) is located at the medial third of the superior margin of the orbit. It transmits blood vessels and the supraorbital nerve, which is an extension of the frontal nerve, a branch of Chapter 1: Orbit and Ocular Adnexa 11 the ophthalmic division (V1) of cranial nerve V (CN V, the trigeminal nerve). The ante- rior ethmoidal foramen is located at the frontoethmoidal 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 transmits the posterior ethmoidal vessels and nerve through the frontal bone (see Fig 1-3). The zygomaticotemporal and zygomatico- facial foramina lie in the portion of the lateral orbital wall formed by the zygomatic bone and transmit vessels and branches of the zygomatic nerve (see Fig 1-5). Nasolacrimal duct The nasolacrimal duct travels inferiorly from the lacrimal sac fossa into the inferior meatus of the nose (see Figs 1-4, 1-40). Infraorbital canal The infraorbital canal continues anteriorly from the infraorbital groove and exits 4 mm below the inferior orbital margin. From there it transmits the infraorbital nerve, a branch of V2 (the maxillary division of CN V) (see Fig 1-1). Fissures The superior orbital fissure (Fig 1-6; see also Fig 1-1) is located between the greater and lesser wings of the sphenoid bone and lies lateral to and partly above and below the optic foramen. It is approximately 22 mm long and is spanned by the tendinous ring formed by the common origin of the rectus muscles (annulus of Zinn). Above the ring, the superior orbital fissure transmits the following structures (Fig 1-7): lacrimal nerve of CN V1 frontal nerve of CN V1 CN IV (trochlear nerve) superior ophthalmic vein Within the ring or between the heads of the rectus muscle are the following (see Fig 1-7): superior and inferior divisions of CN III (the oculomotor nerve) nasociliary branch of CN V1, which also carries the postganglionic sympathetic fibers en route to the ciliary ganglion CN VI (the abducens nerve) Figure 1-6 Axial computed tomography scan of the orbits. The superior orbital fissure (SOF) passes above and below the plane of the optic canal (OC) and is commonly mistaken for the OC. The OC lies in the same plane as the anterior clinoid processes (AClin) and may be cut obliquely in scans so that the entire SOF SOF canal length does not always appear. (Courtesy OC of William R. Katowitz, MD.) AClin AClin 12 Fundamentals and Principles of Ophthalmology Lacrimal nerve Frontal nerve Trochlear nerve (CN IV) Superior ophthalmic vein Superior division Ophthalmic artery of CN III Nasociliary nerve Abducens nerve (CN VI) Inferior division of CN III Inferior ophthalmic vein A Figure 1-7 A, Anterior view of the right orbital apex showing the distribution of the nerves as they enter through the superior orbital fissure and optic canal. This view also shows the annu- lus of Zinn, the fibrous ring formed by the origin of the 4 rectus muscles. (Continued) The course of the inferior ophthalmic vein is variable, and it can travel within or below the ring as it exits the orbit. The inferior orbital fissure lies just below the superior fissure, between the lateral wall and the floor of the orbit, providing access to the pterygopalatine and inferotemporal fos- sae (see Fig 1-1). Therefore, it is close to the foramen rotundum and the pterygoid canal. The inferior orbital fissure transmits the infraorbital and zygomatic branches of CN V2, an orbital nerve from the pterygopalatine ganglion, and the inferior ophthalmic vein. The inferior ophthalmic vein connects with the pterygoid plexus before draining into the cav- ernous sinus. Periorbital Sinuses The periorbital sinuses have a close anatomical relationship with the orbits (Fig 1-8). The medial walls of the orbits, which border the nasal cavity anteriorly and the ethmoid sinus and sphenoid sinus posteriorly, are almost parallel. In adults, the lateral wall of each orbit forms an angle of approximately 45° with the medial plane. The lateral walls border the m iddle cranial, temporal, and pterygopalatine fossae. Superior to the orbit are the anterior cranial fossa and the frontal sinus. The maxillary sinus and the palatine air cells are located inferiorly. 3 1 4 6 12 8 11 10 9 13 SOM LM T SR M MRM 15 11 14 III SO T 10 SO V IV ICA 2 ON VI VV AZ CS CG LA STL 7 V SOV LM IRM SRM VV TG 29 Oph. 18 7 19 16 Max. LG Man. LRM SG 20 17 21 27 5 25 23 14 B 28 24 26 22 Figure 1-7 (continued) B, Top view of the left orbit. AZ, annulus of Zinn; CG, ciliary ganglion; CS, cavernous sinus; ICA, internal carotid artery; IRM, inferior rectus muscle; LA, levator aponeurosis; LG, lacrimal gland; LM, levator muscle; LRM, lateral rectus muscle; Man., mandibular nerve; Max., maxillary nerve; MRM, medial rectus muscle; ON, optic nerve; Oph., ophthalmic nerve; SG, sphenopalatine ganglion; SOM, superior oblique muscle; SOT, superior oblique tendon; SOV, superior ophthalmic vein; SRM, superior rectus muscle; STL, superior transverse ligament; T, trochlea; TG, trigeminal (gasserian) ganglion; VV, vortex veins; 1, infratrochlear nerve; 2, supraorbital nerve and artery; 3, supratrochlear nerve; 4, anterior ethmoid nerve and artery; 5, lacrimal nerve and artery; 6, posterior ethmoid artery; 7, frontal nerve; 8, long ciliary nerves; 9, branch of CN III to medial rectus muscle; 10, nasociliary nerve; 11, CN IV; 12, ophthalmic (orbital) artery; 13, superior ramus of CN III; 14, CN VI; 15, ophthal- mic artery, origin; 16, anterior ciliary artery; 17, vidian nerve; 18, inferior ramus of CN III; 19, sensory branches from ciliary ganglion to nasociliary nerve; 20, motor (parasympathetic) nerve to ciliary ganglion from nerve to inferior oblique muscle; 21, branch of CN III to inferior rectus muscle; 22, short ciliary nerves; 23, zygomatic nerve; 24, posterior ciliary arteries; 25, zygomaticofacial nerve; 26, nerve to inferior oblique muscle; 27, zygomaticotemporal nerve; 28, lacrimal secretory nerve; 29, lacrimal artery and nerve terminal branches. (Part A illustration by Cyndie C.H. Wooley. Part B reproduced from Stewart WB, ed. Ophthalmic Plastic and Reconstructive Surgery. 4th ed. San Francisco: American Academy of Ophthalmology Manuals Program; 1984.) 14 Fundamentals and Principles of Ophthalmology Frontal sinus Frontal sinus Sphenoid sinus Ethmoid Ethmoid sinus sinus Maxillary sinus Maxillary sinus A B Frontal sinus Ethmoid sinus Maxillary sinus Anterior cranial fossa Sphenoid sinus Middle cranial fossa C Figure 1-8 Coronal (A), sagittal (B), and axial (C) views of the anatomical relationship of the 4 periorbital sinuses. (Illustrations by Dave Peace.) Figure 1-9 Coronal computed tomography scan of the orbits and sinuses showing the FE maxillary and ethmoid sinuses. ES = ethmoid sinus; FE = fovea ethmoidalis; IT = inferior ES ST turbinate; MS = maxillary sinus; MT = middle Strut MT turbinate; NS = nasal septum; Ost = ostium of Ost MS IT the maxillary sinus; ST = superior turbinate; Strut = inferomedial orbital strut. (Courtesy of NS William R. Katowitz, MD.) The inferomedial orbital strut is located along the inferonasal orbit, where the orbital bones slope from the floor to the medial wall. This region is significant b ecause of its proximity to the ostium of the maxillary sinus (Fig 1-9). In addition, the fovea ethmoida- lis, which forms the roof of the ethmoid sinuses, is a lateral extension of the cribriform plate. The locations of the periorbital sinuses and their relation to anatomical features of the skull are indicated in Figure 1-8 and discussed further in BCSC Section 7, Oculofacial Plastic and Orbital Surgery. Chapter 1: Orbit and Ocular Adnexa 15 CLINICAL PEARL When lacrimal surgery is planned, it is important to identify the fovea ethmoidalis to prevent inadvertent cerebral spinal fluid leakage as well as intracranial injury. Gospe SM 3rd, Bhatti MT. Orbital anatomy. Int Ophthalmol Clin. 2018;58(2):5–23. Zide BM, Jelks GW. Surgical Anatomy Around the Orbit: The System of Zones. Philadelphia: Lippincott Williams & Wilkins; 2015. Cranial Nerves Six of the 12 cranial nerves (CN II–VII) directly innervate the eye and periocular tissues. Because certain tumors affecting CN I (the olfactory nerve) can give rise to important ophthalmic signs and symptoms, it is imperative that ophthalmologists be familiar with the anatomy of this nerve. Chapter 3 discusses CN I–VII in greater depth; also see BCSC Section 7, Oculofacial Plastic and Orbital Surgery, and Section 5, Neuro-Ophthalmology. Ciliary Ganglion The ciliary ganglion is located approximately 1 cm in front of the annulus of Zinn, on the lateral side of the ophthalmic artery, between the optic nerve and the lateral rectus muscle (Fig 1-10). It receives 3 roots: A long (10–12-mm) sensory root arises from the nasociliary branch of CN V1 and contains sensory fibers from the cornea, the iris, and the ciliary body. A short motor root arises from the inferior division of CN III. It carries pregangli- onic parasympathetic fibers from the Edinger-Westphal nucleus. The fibers of the motor root synapse in the ganglion, and the postganglionic fibers carry parasympa- thetic axons to supply the iris sphincter. A sympathetic root carries postganglionic fibers originating from the superior cervi- cal ganglion, from which they course superiorly with the internal carotid artery. In the cavernous sinus, the sympathetic fibers leave the carotid artery to temporarily join the abducens nerve before entering the orbit either with the nasociliary branch of CN V1 or as an individual root. The sympathetic root enters the orbit through the superior orbital fissure within the tendinous ring, passes through the ciliary gan- glion without synapse, and innervates blood vessels of the eye, as well as the dilator muscle of the pupil. Fibers destined for the Müller muscle travel along the frontal and lacrimal branches of CN V1. Branches of the Ciliary Ganglion Only the parasympathetic fibers synapse in the ciliary ganglion. The sympathetic fi- bers are postganglionic from the superior cervical ganglion and pass through it without 16 Fundamentals and Principles of Ophthalmology Sensory root Short ciliary nerves Oculomotor Nasociliary Ciliary Long ciliary nerve nerve ganglion nerve Trigeminal ganglion Carotid plexus Sympathetic root Maxillary branch Motor root Infraorbital Pterygopalatine nerve ganglion Inferior division of CN III Figure 1-10 Ciliary ganglion. Schematic of the lateral orbit with ciliary ganglion. Note the 3 roots: (1) sensory root, which carries sensation from the globe to the trigeminal ganglion via the nasociliary nerve; (2) sympathetic root carrying postganglionic sympathetic fibers from the superior cervical ganglion and carotid plexus; (3) motor root carrying preganglionic para- sympathetic fibers from the inferior division of the oculomotor nerve. (Modified with permission from Levin LA, Nilsson SFE, Ver Hoeve J, Wu SM. Adler’s Physiology of the Eye. 11th ed. Philadelphia: Elsevier/Saunders; 2011:364.) s ynapsing. Sensory fibers from cell bodies in the trigeminal ganglion carry sensation from the eye, orbit, and face. Together, the nonsynapsing sympathetic fibers; the sensory fibers; and the myelinated, fast-conducting postganglionic parasympathetic fibers form the short ciliary nerves (see also Chapter 3, Fig 3-18). Short Ciliary Nerves There are 2 groups of short ciliary nerves, totaling 6–10, which arise from the ciliary ganglion (see Fig 1-10). They travel on both sides of the optic nerve and, together with the long ciliary nerves, pierce the sclera around the optic nerve (see Fig 1-19). Both long and short ciliary nerves pass anteriorly between the choroid and the sclera to the ciliary muscle, where they form a plexus that supplies the cornea, the ciliary body, and the iris. The long ciliary nerves, which arise directly from the nasociliary branch of CN V1 (oph- thalmic division of the trigeminal neve), are sensory nerves. The short ciliary nerves are both sensory and motor nerves, carrying autonomic fibers to the pupil and ciliary muscles (see Chapter 3). Chapter 1: Orbit and Ocular Adnexa 17 Extraocular Muscles There are 7 extraocular muscles (Figs 1-11 through 1-14, Table 1-1, Activity 1-1): medial rectus lateral rectus superior rectus inferior rectus superior oblique inferior oblique levator palpebrae superioris ACTIVITY 1-1 Interactive model of the extraocular muscles. Activity developed by Mary A. O’Hara, MD. Access all Section 2 activities at www.aao.org/bcscactivity_section02. Superior oblique muscle Superior rectus muscle Trochlea Medial rectus muscle Superior oblique Annulus of Zinn tendon Inferior rectus muscle Inferior oblique muscle Figure 1-11 Extraocular muscles, lateral composite (sagittal) view of the left eye. (Reproduced with permission from Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy. Philadelphia: Saunders; 1994.) Levator palpebrae superioris muscle Superior oblique tendon Trochlea Superior rectus tendon Medial rectus tendon Lateral rectus tendon Inferior oblique muscle Inferior rectus tendon Figure 1-12 Extraocular muscles, frontal view of the left eye, coronal plane. (Reproduced with permission from Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy. Philadelphia: Saunders; 1994.) 18 Fundamentals and Principles of Ophthalmology Levator palpebrae superioris muscle Trochlea Superior oblique muscle Superior rectus muscle Superior orbital fissure Medial rectus muscle Lateral rectus muscle Annulus of Zinn Inferior oblique muscle Inferior rectus muscle Figure 1-13 Extraocular muscles, frontal view, left eye, with globe removed. (Reproduced with permission from Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy. Philadelphia: Saunders; 1994.) Annulus of Zinn Inferior rectus muscle Medial rectus Lateral rectus muscle muscle Superior oblique tendon Superior rectus tendon Figure 1-14 Extraocular muscles, superior composite (axial) view. (Reproduced with permission from Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy. Philadelphia: Saunders; 1994.) Extraocular Muscle Origins The annulus of Zinn consists of superior and inferior orbital tendons and is the origin of the 4 rectus muscles (Fig 1-15). The upper tendon gives rise to the entire superior rectus muscle, as well as portions of the lateral and medial rectus muscles. The inferior tendon gives rise to the entire inferior rectus muscle and portions of the medial and lateral rectus muscles. The levator palpebrae superioris muscle arises from the lesser wing of the sphe- noid bone, at the apex of the orbit, just superior to the annulus of Zinn (see the section “Levator palpebrae superioris muscle” later in the chapter). The superior oblique muscle originates from the periosteum of the body of the sphe- noid bone, above and medial to the optic foramen. The inferior oblique muscle originates anteriorly, from a shallow depression in the orbital plate of the maxillary bone, at the anteromedial corner of the orbital floor, near the fossa for the lacrimal sac. From its origin, the inferior oblique muscle then extends posteriorly, laterally, and superiorly to insert into the globe (see Table 1-1). Table 1-1 Comparison of the Extraocular Muscles Muscle Origin Insertion Size Blood Supply Nerve Supply Medial Annulus of Medially, in 40.8 mm long; Medial (inferior) Inferior division rectus Zinn horizontal tendon: muscular of CN III meridian 3.7 mm long, branch of (oculomotor) 5.5 mm 10.3 mm wide ophthalmic from limbus artery Inferior Annulus of Inferiorly, in 40 mm long; Medial (inferior) Inferior division rectus Zinn at vertical tendon: muscular of CN III orbital meridian 5.5 mm long, branch of (oculomotor) apex 6.5 mm from 9.8 mm wide ophthalmic limbus artery and infraorbital artery Lateral Annulus Laterally, in 40.6 mm long; Lateral CN VI rectus of Zinn horizontal tendon: 8 mm (superior) (abducens) spanning meridian long, 9.2 mm muscular the 6.9 mm from wide branch of superior limbus ophthalmic orbital artery and fissure lacrimal artery Superior Annulus of Superiorly, 41.8 mm long; Lateral Superior rectus Zinn at in vertical tendon: (superior) division orbital meridian 5.8 mm long, muscular of CN III apex 7.7 mm from 10.6 mm wide branch of (oculomotor) limbus ophthalmic artery Superior Medial to To trochlea, 40 mm long; Lateral CN IV (trochlear) oblique optic through tendon: (superior) foramen, pulley, just 20 mm long, muscular between behind orbital 10.8 mm wide branch of annulus of rim, then ophthalmic Zinn and hooking back artery periorbita under superior rectus, inserting posterior to center of rotation Inferior From a Posterior 37 mm long; Medial (inferior) Inferior division oblique depression inferotemporal tendon: 1 mm muscular of CN III on orbital quadrant long, 9.6 mm branch of (oculomotor) floor near at level of wide at ophthalmic orbital rim macula; insertion artery and (maxilla) posterior infraorbital to center of artery rotation Levator Lesser Trochlea, 60 mm long; Branches of the Superior palpebrae wing of supraorbital muscle: ophthalmic division superioris sphenoid notch, superior 40 mm, artery of CN III bone tarsus, tendon: (oculomotor) lateral orbital 14–20 mm tubercle, posterior lacrimal crest CN = cranial nerve. 20 Fundamentals and Principles of Ophthalmology Levator palpebrae superioris muscle Superior rectus muscle Optic nerve Superior orbital fissure Superior oblique muscle Oculomotor foramen Ophthalmic artery Lateral rectus muscle Medial rectus muscle Annulus of zinn Inferior rectus muscle Figure 1-15 Origin of the extraocular muscles. All extraocular muscles, except the inferior oblique, originate in the orbital apex. The 4 rectus muscles share a common fibrotendinous ring known as the annulus of Zinn. Note that the superior rectus and medial rectus are juxta- posed to the optic nerve sheath; this is the reason that patients with retrobulbar optic neuritis experience pain with movement of the eye. (Reproduced with permission from Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy. 2nd ed. Philadelphia: Elsevier/Saunders; 2011, Fig 3-8.) Extraocular Muscle Insertions The 4 rectus muscles insert anteriorly on the globe. Starting at the medial rectus mus- cle and proceeding to the inferior rectus, lateral rectus, and superior rectus muscles, the muscle insertions lie progressively farther from the limbus. An imaginary curve drawn through these insertions creates a spiral, called the spiral of Tillaux (Fig 1-16). The re- lationship between the muscle insertions and the location of the ora serrata is clinically important. A misdirected suture passed through the insertion of the superior rectus mus- cle could perforate the retina. The superior oblique muscle, a fter passing through the trochlea in the superomedial orbital rim, inserts onto the sclera superiorly, under the insertion of the superior rec- tus. The inferior oblique muscle inserts onto the sclera in the posterior inferotemporal quadrant. Extraocular Muscle Distribution in the Orbit See Figures 1-12 through 1-14 for the arrangement of the extraocular muscles within the orbit. Note the relationship between the oblique extraocular muscles and the superior, medial, and inferior rectus muscles. See Chapter 17 for additional figures depicting the location of the extraocular muscles within the orbit and their relationship to surround- ing structures, along with corresponding computed tomography and magnetic resonance imaging scans. Chapter 1: Orbit and Ocular Adnexa 21 Superior rectus tendon Superior oblique tendon 7.7 Spiral of Tillaux Lateral rectus tendon 6.9 5.5 Medial rectus tendon 6.5 Inferior rectus tendon Inferior oblique muscle Figure 1-16 The medial rectus tendon is closest to the limbus, and the superior rectus tendon is farthest from it. By connecting the insertions of the tendons beginning with the medial rectus, then the inferior rectus, then the lateral rectus, and finally the superior rectus, a spiral (known as the spiral of Tillaux) is obtained. Measurements are in millimeters. The anterior cili- ary arteries are also shown. (Illustration by Christine Gralapp.) Blood Supply to the Extraocular Muscles The extraocular muscles are supplied by the following (see T able 1-1): muscular branches of the ophthalmic artery infraorbital artery lacrimal artery The muscular branches of the ophthalmic artery give rise to the anterior ciliary arter- ies and can be divided into lateral (superior) and medial (inferior) branches. Each rec- tus muscle has 1–4 anterior ciliary arteries, which eventually pass through the mu

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