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دانلود کتاب Retina
دانلود کتاب شبکیه چشم
مشخصات کتاب
Retina
ویرایش: 5th
نویسندگان: Stephen J. Ryan et al.
سری:
ISBN (شابک) : 1455707376, 9781455707379
ناشر: Saunders
سال نشر: 2012
تعداد صفحات: 796
زبان: English
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود)
حجم فایل: 119 مگابایت
قیمت کتاب (تومان) : 50,000
کلمات کلیدی مربوط به کتاب شبکیه چشم: چشم پزشکی، جراحی، پزشکی، چشم پزشکی، بالینی، پزشکی، پزشکی و علوم بهداشتی، کتاب های درسی جدید، مستعمل و اجاره ای، بوتیک تخصصی
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توضیحاتی در مورد کتاب شبکیه چشم
جوایز کتاب پزشکی BMA 2013 در تخصص های جراحی بسیار ستایش شده است!
بی نظیر از نظر دامنه، عمق و دقت بالینی، رتینا، ویرایش پنجم b> شما را در خط مقدم فناوری‌های جدید، رویکردهای جراحی و گزینه‌های تشخیصی و درمانی بیماری‌ها و اختلالات شبکیه چشم نگه می‌دارد. به‌طور کامل به‌روزرسانی شده تا همه چیزهایی را که باید در مورد تشخیص، درمان، توسعه، ساختار، عملکرد و پاتوفیزیولوژی شبکیه بدانید، منعکس می‌کند. چهره در عمل. \"فصل ها وضوح، اقتدار و وسعت را نشان می دهند که همراه با تصاویر و ویدیوهای فوق العاده منجر به یک کتاب برجسته می شود.\" بررسی شده توسط: B.R.Masters، Independent Scholar از طرف از مجله Graefe's Archive for Clinical and Experimental Ophthalmology، ژانویه 2014
- از دانش و تجربه گسترده سردبیر محترم دکتر استفان رایان، پنج نفر از سردبیران متخصص، بهره مند شوید. و یک دیدگاه واقعا جهانی از 358 مقام جهانی دیگر در سراسر اروپا، آسیا، استرالیا و آمریکا.
- آزمایش و ارزیابی جدیدترین فناوری‌ها و رویکردهای تشخیصی که مدیریت بیماری شبکیه را تغییر می‌دهند. از جمله فناوری‌های آینده که به زودی به استاندارد تبدیل خواهند شد.
- آخرین اکتشافات علمی و ژنتیکی، روش‌های تصویربرداری تشخیصی، درمان‌های دارویی، توصیه‌های درمانی، و تکنیک‌های جراحی را در کار قرار دهید. تمرین شما.
- از فناوری های جدید بهترین استفاده را ببرید با پوشش گسترده و به روز توموگرافی انسجام نوری (OCT)، تصویربرداری فوندوس، و تصویربرداری اتوفلورسانس .
- آخرین دانش در مورد درمان ضد VEGF را برای دژنراسیون ماکولا مرتبط با سن، رتینوپاتی دیابتی و بیماری ورید به کار ببرید.
- درباره بینایی مصنوعی بیاموزید. ، تحویل دارو به بخش خلفی، پیشرفت در جراحی ماکولا، ویترکتومی، و جداشدگی پیچیده شبکیه، با به روز رسانی در مورد تومورها، ژنتیک شبکیه، زیست شناسی سلولی، موضوعات مهم علوم پایه، و موارد دیگر.
- از رویکردهای دارویی جدید بیشترین بهره را ببرید در مدیریت دژنراسیون ماکولا وابسته به سن و رتینوپاتی دیابتی.
- در عمل خود، ارزیابی‌های تشخیصی، و اکنون حتی درمان‌ها ، تحت تأثیر اکتشافات علمی اخیر قرار خواهد گرفت از جمله در زمینه های نانوتکنولوژی، محافظت از عصبی، سلول های بنیادی و ژن درمانی، در میان سایر مشارکت های علمی.
- مشاهده ویدیوهای روش های جراحی < /b>و به محتویات کامل Retina، نسخه پنجم آنلاین در www.expertconsult.com به طور کامل دسترسی داشته باشید. قابل جستجو، با به روز رسانی های معمول و گالری تصاویر قابل دانلود.
توضیحاتی درمورد کتاب به خارجی
2013 BMA Medical Book Awards Highly Commended in Surgical Specialties!
Unequalled in scope, depth, and clinical precision, Retina, 5th Edition keeps you at the forefront of today's new technologies, surgical approaches, and diagnostic and therapeutic options for retinal diseases and disorders. Comprehensively updated to reflect everything you need to know regarding retinal diagnosis, treatment, development, structure, function, and pathophysiology, this monumental ophthalmology reference work equips you with expert answers to virtually any question you may face in practice. "The chapters demonstrate clarity, authority, and breadth which together with superb illustrations and videos result in an outstanding book." Reviewed by: B.R.Masters, Independent Scholar on behalf of Graefe's Archive for Clinical and Experimental Ophthalmology journal, Jan 2014
- Benefit from the extensive knowledge and experience of esteemed editor Dr. Stephen Ryan, five expert co-editors, and a truly global perspective from 358 other world authorities across Europe, Asia, Australasia the Americas.
- Examine and evaluate the newest diagnostic technologies and approaches that are changing the management of retinal disease, including future technologies which will soon become the standard.
- Put the very latest scientific and genetic discoveries, diagnostic imaging methods, drug therapies, treatment recommendations, and surgical techniques to work in your practice.
- Make the best use of new technologies with expanded and updated coverage of optical coherence tomography (OCT), fundus imaging, and autofluorescence imaging.
- Apply the latest knowledge on anti-VEGF therapy for age related macular degeneration, diabetic retinopathy and vein disease.
- Learn about artificial vision, drug delivery to the posterior segment, advances in macular surgery, vitrectomy, and complex retinal detachment, with updates on tumors, retinal genetics, cell biology, important basic science topics, and much more.
- Get the most out of new pharmacologic approaches in the management of age-related macular degeneration and diabetic retinopathy.
- In your practice, diagnostic evaluations, and now even treatments, will be influenced by recent scientific discoveries such as in the areas of nanotechnology, neuro protection, stem cells and gene therapy, among other scientific contributions.
- View videos of surgical procedures and access the complete contents of Retina, 5th Edition online at www.expertconsult.com, fully searchable, with regular updates and a downloadable image gallery.
فهرست مطالب
Retina Title Copyright page Contributors Dedication Foreword Preface Video Table of Contents Complications in Vitreoretinal Surgery Always Measure Prior to Trochar Insertion Suprachoroidal Infusion Subretinal Insertion of Endo-illuminator Dislocated IOL and Capsular Tension Ring Iatrogenic Breaks during the Induction of Posterior Vitreous Detachment Iatrogenic Macular Hole during VMT Surgery Iatrogenic Breaks during the Delamination of Diabetic Traction Retinal Detachment Point Pressure Hemostasis during Diabetic Vitrectomy Iatrogenic Retinal Break during ERM Peeling Subretinal Brilliant Blue Peripheral Retinal Detachment during Macular Hole Surgery Subretinal Hemorrhage Macular Fold Subretinal Perfluorocarbon Subretinal Perfluorocarbon Injection during En Bloc Perfluorodissection Intraocular Foreign Body Dislodged on the Macula Suprachoroidal Hemorrhage Hemorrhagic Choroidal Detachment after “One Stitch” Vitrectomy Surgery Dislocated Phakic IOL Dislocation of the Tip of the Soft Tip Cannula Iatrogenic Peripheral Retinal Breaks during IOFB Extraction Peri-silicone Proliferation Miragel Buckle Removal Subconjunctival Silicone Oil Removal List of Video Contributors VOLUME 1 Part 1: Retinal Imaging and Diagnostics Section 1: Optimal Imaging Technologies 1 Fluorescein Angiography: Basic Principles and Interpretation Basic principles Fluorescence Pseudofluorescence Equipment Film-based versus digital fluorescein angiography – historical perspectives Camera and auxiliary equipment Stereophotography Matched fluorescein filters Light sources (viewing bulb and flash strobe) Fluorescein solution Technique Aligning camera and photographing Focusing Digital angiography Using stereophotography Photographing the periphery Informing the patient Positioning the patient Injecting the fluorescein Developing a photographic plan Diabetic retinopathy Interpretation Fundus anatomy and histology Normal fluorescein angiogram Abnormal fluorescein angiogram Hypofluorescence Anatomic location of hypofluorescence Blocked retinal fluorescence Blocked choroidal fluorescence Deep retinal material Subretinal material Vascular filling defect Retinal vascular filling defect Vascular filling defects of the disc Choroidal vascular filling defect Hyperfluorescence Preinjection fluorescence Autofluorescence Transmitted fluorescence (pigment epithelial window defect) Abnormal retinal and disc vessels Abnormal choroidal vessels Leak Vitreous leak Disc leak Papilledema and optic disc edema Retinal leak Choroidal leak Staining Drusen Scar Sclera Acknowledgments References 2 Clinical Applications of Diagnostic Indocyanine Green Angiography Introduction History Chemical and pharmacokinetics Toxicity Instrument comparison Injection technique Indocyanine green angiography interpretation Normal eye Exudative age-related macular degeneration Type 1 choroidal neovascularization Type 2 choroidal neovascularization Type 3 choroidal neovascularization Polypoidal choroidal vasculopathy Central serous chorioretinopathy Choroidal tumors Choroidal hemangioma Choroidal melanoma Peripheral exudative hemorrhagic chorioretinopathy Varix of the vortex vein ampulla Choroidal inflammation and white-dot syndrome Multiple evanescent white-dot syndrome Multifocal choroiditis Birdshot chorioretinopathy Acute multifocal placoid pigment epitheliopathy Serpiginous choroidopathy Punctate inner chorioretinopathy Acute zonal occult outer retinopathy Conclusions References 3 Optical Coherence Tomography Physical principles of optical coherence tomography Quantitative analysis of OCT datasets Normal macular anatomy SD-OCT IN retinal disorders Vitreoretinal interface disorders Vitreomacular traction Epiretinal membrane Macular hole Age-related macular degeneration Non-neovascular AMD (see Chapter 65, Dry AMD – diagnosis and treatment) Early non-neovascular AMD: drusen and pigmentary changes Late non-neovascular AMD: geographic atrophy Neovascular AMD (see Chapter 66, Wet AMD – diagnosis and treatment) Intraretinal and subretinal fluid Retinal pigment epithelium detachment Tear of the retinal pigment epithelium Disciform scarring Retinal angiomatous proliferation Polypoidal choroidal vasculopathy Choroidal neovascularization: response to treatment Central serous chorioretinopathy Enhanced depth imaging OCT IN CSC Cystoid macular edema Diabetic retinopathy Nonproliferative diabetic retinopathy and diabetic macular edema Proliferative diabetic retinopathy Retinal vein occlusion Central retinal artery occlusion Branch retinal artery occlusion Future directions Disclosures References 4 Autofluorescence Imaging Basic principles Fundus autofluorescence Retinal pigment epithelium and lipofuscin Near-infrared autofluorescence Macular pigment imaging Techniques of fundus autofluorescence imaging Fundus spectrophotometer Scanning laser ophthalmoscopy Fundus camera Wide-field imaging Interpretation of fundus autofluorescence images Clinical applications Age-related macular degeneration Early AMD Geographic atrophy Pigment epithelium detachment Choroidal neovascularization Macular and diffuse retinal dystrophies Macular telangiectasia Pseudoxanthoma elasticum Central serous chorioretinopathy Chloroquine and hydroxychloroquine retinopathy Functional correlates of FAF abnormalities References 5 Advanced Imaging Technologies Introduction – retinal imaging to date Adaptive optics – imaging of single cells in the retina Basic principles Technology Visualization of retinal structures Early clinical applications Conclusions Doppler imaging – assessment of blood flow Basic principles Non-Doppler assessment of retinal blood flow Doppler ultrasound Laser Doppler velocimetry Laser Doppler flowmetry Doppler optical coherence tomography Conclusions Spectral imaging – assessment of retinal oxygenation Basic principles Technology Clinical applications Conclusions Photoacoustic imaging – assessment of retinal absorption Basic principles Technology Conclusions Magnetic resonance imaging Basic principles Retinal imaging Conclusions Nanotechnology Basic principles Iron oxide nanoparticles Gold nanoparticles Quantum dots Conclusions Conclusions and future directions Disclosure References 6 Image Processing Introduction History of retinal imaging History of retinal image processing Current status of retinal imaging Fundus imaging Optical coherence tomography imaging Time domain OCT Frequency domain OCT Spectral domain OCT Swept source OCT Areas of active research in retinal imaging Portable, cost-effective fundus imaging Functional imaging Adaptive optics Longer-wavelength OCT imaging Clinical applications of retinal imaging Early detection of diabetic retinopathy Early detection of systemic disease from fundus photography Image-guided therapy for retinal diseases with 3D OCT Image analysis concepts for clinicians The retinal image Definition of a retinal image Retinal image quantities Retinal image compression Lossy image compression Legal issues with lossy image compression Storing and accessing retinal images: ophthalmology picture-archiving systems Different strategies for storing ophthalmic images Digital exchange of retinal images and DICOM Retinal image analysis Common image-processing steps Preprocessing Detection Segmentation Registration Interpretation Unsupervised and supervised image analysis Pixel feature classification Measuring performance of image analysis algorithms Sensitivity and specificity Receiver operator characteristics Repeatability and variability The reference standard or gold standard Clinical safety relevant performance measurement Fundus image analysis Detection of retinal vessels Detection of fovea and optic disc Detection of retinal lesions Vessel analysis Retinal atlas Performance of DR detection algorithms Areas of active research in fundus image analysis OPTICAL COHERENCE TOMOGRAPHY image analysis Retinal layer analysis from 3D OCT Retinal layer detection OCT image flattening Retinal layer thickness analysis Retinal texture analysis Detection of retinal vessels from 3D OCT Detection of retinal lesions Fluid detection and segmentation Fluid segmentation in 3D Intraretinal layer segmentation in the presence of SEADs Multimodality retinal imaging Registration of fundus retinal photographs Registration of OCT with fundus retinal photographs Mutual registration of 3D OCT images Future of retinal imaging and image analysis References Section 2: Retinal Diagnostics 7 Electrogenesis of the Electroretinogram Introduction Generation of extracellular potentials: general concepts Spatial buffering by glial cells Approaches for determining the origins of the electroretinogram Intraretinal depth recordings Correlation of ERG with single-cell recordings Pharmacologic dissection Site-specific lesions/pathology or targeted mutations Modeling of cellular responses and ERG components Standard ERG tests in the clinic Distal retinal components: slow PIII, C-wave, fast oscillation trough, and light peak c-Wave Müller cell contribution (slow PIll) Distal versus proximal PIII Retinal pigment epithelial component The fast oscillation trough The light peak Origin of the A-wave The a-wave as a reflection of rod and cone receptor photocurrent Postreceptoral contributions to the a-wave The timecourse of the photoreceptor response Origin of the b-wave Müller cell hypothesis ON bipolar cells as the generator of the b-wave Scotopic b-wave (PII) in mammals Cone-driven b-wave Origin of the d-wave Photopic hill Origin of the photopic fast-flicker ERG Origin of the multifocal ERG ERG waves from proximal retina Origin of the proximal negative response and the M-wave Origin of the photopic negative response Relation to the pattern ERG Origin of the scotopic threshold response K+ Müller cell mechanism for generation of the STR Neuronal origins of the STR Origin of oscillatory potentials Do all the OPs have the same origin? Which cells generate the OPs? What mechanisms are involved in generating OPs? Neuronal interaction; inhibitory feedback circuits OPs in intracellular responses from neurons Closing remarks References 8 Clinical Electrophysiology Standard full-field ERG Stimulus and recording devices Stimulus intensity versus ERG responses and components Scotopic condition Photopic condition Bright flash mixed rod–cone ERG Normal Selectively abnormal oscillatory potentials Subnormal Negative Prognostic value Diagnostic value Extinct Isolation of rod and cone components in standardized ERG Cone photoreceptor dysfunction Rod photoreceptor dysfunction Rod–cone or cone–rod photoreceptor dystrophy Second-order neuron dysfunction Focal ERG Principle, method, and characteristics Clinical applications Other special responses or techniques in ERG Pattern ERG Photopic negative response ERG recordings by LED ERG recording under general anesthesia ERG monitoring during eye surgery S-Cone ERG Electro-Oculogram Visual Evoked Potential References 9 Diagnostic Ophthalmic Ultrasound Introduction Ultrasound – past and present Examination techniques A-mode technique B-mode technique High-frequency ultrasound technique Doppler ultrasound Ultrasound biometry Three-dimensional reconstructions Ultrasound in intraocular pathology Changes in the shape of the globe Staphyloma Scleral buckle Microphthalmos Phthisis Vitreous Vitreous degeneration Asteroid hyalosis Synchysis scintillans Persistent and hyperplastic primary vitreous Vitreous hemorrhages Vitreous hemorrhage from neovascularization Terson syndrome Intraocular infections Vitreous inflammation Intraocular foreign bodies Retina Acute retinal detachment Chronic retinal detachment Retinoschisis Coats disease Retinoblastoma Retinopathy of prematurity Optic nerve Coloboma of the ocular fundus Assessment of optic nerve cupping Choroid Changes in the ocular layers due to hypotony Choroidal neovascularization Choroidal melanoma The characteristics of a choroidal melanoma on B-mode echography The characteristics of a choroidal melanoma on A-mode ultrasonography Determining the volume of a choroidal melanoma by ultrasonography The role of ultrasonography for planning the treatment of choroidal melanomas Metastatic choroidal tumors Choroidal hemangioma Choroidal osteoma – metastatic calcifications Choroidal tuberculoma The uveal effusion syndrome Sclera Posterior scleritis Ultrasound imaging used to differentiate ocular disease Future developments Acknowledgments References 10 Color Vision and Night Vision Overview Rod and cone functions Light adaptation Spectral sensitivity Spatial and temporal resolution Visual pathways for rod and cone functions Retinal pathways Retinogeniculate pathways Dark adaptation functions: assessment of the shift from day vision to night vision Clinical evaluation using dark adaptation functions Color vision Color matching Color matching as the foundation for the theory of trichromacy Color-matching experimental techniques and data The CIE colorimetric system Cone chromaticity space Chromatic discrimination Wavelength discrimination Purity discrimination Chromaticity discrimination Color appearance Variations in human color vision Color vision classifications The genes encoding the human photopigments Clinical evaluation of color vision Screening tests Pseudoisochromatic plate tests Other rapid tests of color vision Chromatic discrimination ability tests Importance of the test illuminant for plate and discrimination color vision tests Color-matching tests Anomaloscope color matching test using the Rayleigh equation Anomaloscope color-matching test using the Moreland equation Considerations in the use of anomaloscopes Computerized color vision tests Color assessment and diagnosis (CAD) test Cambridge color test (CCT) The portal color sort test (PCST) Smartphone/tablet applications for color vision screening Which test to use in a clinical setting? New developments in color vision research Gene therapy for color vision defects Adaptive optics (AO) retinal imaging system Rod and cone interactions in color vision Acknowledgments References 11 Visual Acuity and Contrast Sensitivity Visual acuity tests Introduction Chart design Optotypes Chart layout Testing procedure Acuity test distance Luminance and contrast Test administration Scoring Near and reading acuity tests Specifying letter size Words versus continuous text Electronic acuity tests Contrast sensitivity tests Introduction Utility of contrast sensitivity tests Methods Common contrast sensitivity tests Gratings versus optotypes Test design and procedure Interpretation of clinical versus statistical significance: an example from the literature References 12 Visual Fields in Retinal Disease Principles of perimetry The island of Traquair Methods of visual field testing Qualitative techniques Quantitative techniques Other methodologies of visual field testing in retinal disease Reliability and reproducibility of visual field tests Perimetry in specific retinal diseases Retinal dystrophies Diabetic retinopathy Other vascular diseases and nondiabetic macular edema Age-related macular degeneration and other maculopathies Macular holes and epiretinal membrane Toxic retinopathies Infectious and inflammatory retinopathies Retinal detachment Tumors Future of perimetry in retinal disease Layer-by-layer perimetry Color perimetry High-resolution OCT and adaptive optics with microperimetry Conclusions References Part 2: Basic Science and Translation to Therapy Section 1: Anatomy and Physiology 13 The Development of the Retina Embryology of the eye The eye field Patterning the retinal, RPE, and anterior domains of the optic cup Histogenesis of the retinal cell types Inner retinal development Photoreceptor development Ganglion cell death Retinal maturation Conclusion References 14 Structure and Function of Rod and Cone Photoreceptors Introduction Photoreceptor fundamentals Photoreceptor outer-segment structure Proteins that stabilize the structure of outer-segment discs Disc morphogenesis Outer-segment plasma membrane Outer-segment lipids Phototransduction Signal activation and amplification Signal deactivation Quenching R*: phosphorylation and arrestin binding Deactivating PDE: control of transducin’s GTPase activity Resynthesis of cGMP: Ca2+ dependence of guanylyl cyclase Light adaptation The role of Ca2+ feedback Adaptation mediated by Ca2+ feedback to retinal guanylyl cyclase Recoverin and control of rhodopsin kinase Feedback regulation of the cGMP-gated channel Other (Ca2+-independent) adaptation mechanisms: protein translocation Differences between rod and cone phototransduction Inner segment and connecting cilia Inner segment Targeting of phototransduction proteins from the inner segment to the outer segment The connecting cilium Nucleus Photoreceptor synaptic terminal Photoreceptor dysfunction and disease Rhodopsin mutations Constitutive phototransduction and retinal disease Transducin defects and retinal disease cGMP and photoreceptor cell physiology References 15 Function and Anatomy of the Mammalian Retina Visual illusions and multiple channels The retina is a piece of brain Neuronal communication: chemical and electrical The retina is a layered structure Gross retinal morphology The fovea The blind spot and how to find it Painting the retina – techniques to label and visualize retinal neurons Six major neuronal cell classes Classification of retinal cells Photoreceptors Cones Rods Cone pedicles and rod spherules Photoreceptor coupling Photoreceptors release glutamate in the dark Second-order neurons: horizontal and bipolar cells Horizontal cell function Bipolar cell function OFF cone bipolar cells ON cone bipolar cells Midget bipolar cells Blue cone bipolar cells Rod bipolar cells Multiple rod pathways Secondary and tertiary rod pathways Amacrine cells AII amacrine cells S1 and S2 amacrine cells Dopaminergic amacrine cells Starburst amacrine cells Ganglion cells Does each ganglion cell type represent a visual channel? A ganglion cell for the control of pupil diameter and circadian rhythm Color vision and ganglion cells Gene therapy to cure color blindness New tools to identify ganglion cell types Clinical relevance of functional anatomy Conclusions Acknowledgments References 16 Cell Biology of the Retinal Pigment Epithelium Embryology Anatomy and histology Heterogeneity and polarity of the RPE Cellular junctions Cytoskeleton Role of RPE in Bruch’s membrane synthesis and remodeling Cell culture models of RPE specialized functions of the RPE Absorption of light Phagocytosis of rod outer segments Role in visual cycle Protection from oxidative stress Role in maintaining avascular outer retina Immune privilege Transport of nutrients, ions, and water Secretion of cytokines and growth factors Acknowledgments References 17 Cell Biology of the Müller Cell Introduction Morphology of müller cells Müller cells constitute the cores of functional retinal columns Light guidance Recycling of cone photopigments Regulation of the synaptic activity by neurotransmitter uptake Malfunction of glial glutamate uptake contributes to glutamate toxicity Production of neurotransmitter precursors Trophic support of photoreceptors and neurons Antioxidative support of photoreceptors and neurons Removal of carbon dioxide Regulation of the extracellular pH Spatial potassium buffering Water clearance Contribution to edema development and resolution Regulation of the blood–retinal barrier Mediation of neurovascular coupling Regulation of the extracellular space volume Responses to mechanical stress Regulation of neuronal activity by release of gliotransmitters Ionotropic receptors of Müller cells Müller cell gliosis Müller stem cells References 18 Retinal and Choroidal Vasculature: Retinal Oxygenation Introduction Comparison of retinal and choroidal vasculatures History of retinal ischemia Normoxia Hyperoxia Hypoxia Hypoxia-inducible factor HIF deficiency and its resultant pathology HIF-activated genes relevant to physiological and pathological ocular angiogenesis VEGF in health and in ocular disease Bone marrow-derived progenitor cells (BMPC) and vascular repair Disease-associated BMPC dysfunction Key factors that modulate VEGF function in the retina Adult retinal hypoxia and etiology Diabetic retinopathy Retinal vein occlusion (RVO) Sickle-cell disease (SCD) Ocular ischemic syndrome (OIS) Retinal detachment Consequences of retinal ischemia Vascular permeability Adult choroidal ischemia Conclusions References 19 Mechanisms of Normal Retinal Adhesion Models for measuring retinal adhesion In vitro methods In vivo methods Adhesive force and environmental factors Magnitude of adhesive force Sensitivity to temperature and ionic environment Mechanical forces outside the subretinal space Fluid pressure: hydrostatic and osmotic Vitreous support and other physical aspects of adhesion Mechanical forces inside the subretinal space Mechanical interdigitation Interphotoreceptor matrix properties Subcellular components and mobility Metabolic factors Critical dependence on oxygen Metabolic inhibitors and other agents Relationship of adhesion to subretinal fluid transport and subretinal protein Pharmacologic modification of adhesion Mannitol Acetazolamide Cold temperature and ouabain Ionic changes Implications for vitreoretinal surgery Recovery after rhegmatogenous retinal detachment Recovery of adhesiveness without retinopexy Effects of retinopexy Effects of vitreous in the subretinal space Pathophysiology of serous detachment Conclusions and general implications References 20 Structure, Function, and Pathology of Bruch’s Membrane Introduction, history, embryology Early history Development of Bruch’s membrane Structure of Bruch’s membrane in the young adult eye RPE basal lamina (RPE-BL) Inner collagenous layer (ICL) Elastic layer (EL) Outer collagenous layer Choriocapillaris basal lamina (ChC-BL) Bruch’s membrane in an aged eye Lipid accumulation: Bruch’s membrane lipoproteins Other aging changes Function of Bruch’s membrane Structural role of Bruch’s membrane Transport role of Bruch’s membrane Hydraulic conductivity of Bruch’s membrane Age-related changes in hydraulic conductivity and disease Permeability of Bruch’s membrane to solute transport Summary and implications Pathology of Bruch’s membrane AMD lesions Drusen Basal linear deposit Basal laminar deposit Subretinal drusenoid debris Summary Response-to-retention hypothesis of AMD Neovascular AMD Angioid streaks (ABCC6, MTP genes) Thick basal laminar deposits (TIMP-3, CTRP5, EFEMP1 genes) Conclusion References 21 Vitreous and Vitreoretinal Interface Biochemistry of vitreous Collagen Hyaluronan Chondroitin sulfate Noncollagenous structural proteins Fibrillins Opticin Anatomy and histology Vitreous body Vitreoretinal interface Posterior vitreous cortex Hyalocytes Internal limiting lamina (ILL) of the retina Retinal sheen dystrophy Degenerative remodeling Vitreoretinal interface Topographic variations Strength of vitreoretinal adhesion Peripheral fundus and vitreous base Interface along major retinal vessels Vitreomacular interface Vitreopapillary interface Physiology Biochemical Biophysical Age-Related Vitreous Degeneration Liquefaction (synchysis) Pathogenesis of vitreous liquefaction Aging changes and vitreous biochemistry Structural changes Vitreous body Aging changes at the vitreoretinal interface Posterior vitreous detachment Epidemiology Symptomatic PVD Anomalous PVD (APVD) Vitreous effects of APVD Peripheral retinal effects of APVD Retinal breaks Other sequelae Macular effects of APVD Vitreomacular traction Exudative age-related macular degeneration Cystoid macular edema Macular cysts Macular holes Histopathology and pseudo-operculum Pathogenesis Optic disc effects Vitreoretinal Changes after Lens Extraction Structural Biochemical PVD Inflammatory Vitreoretinal changes after trauma Blunt trauma Shaken-baby syndrome Posterior penetrating and perforating trauma Periretinal proliferation Premacular membranes Retroretinal membranes Complex membranes References Section 2: Basic Mechanisms of Injury in the Retina 22 Mechanisms of Oxidative Stress in Retinal Injury Overview of oxidative stress in the retina Retinal diseases related to oxidative stress Age-related macular degeneration Diabetic retinopathy Inherited retinal degenerations Oxidative injury to the retina Retinal pigment epithelium Retinal vasculature Photoreceptors Mitochondria Oxidative stress and inflammation Retinal therapies targeting oxidative stress Supplemental antioxidants Dietary antioxidants Anti-advanced glycation end-product treatment Genetic modification Conclusions References 23 Mechanisms of ER Stress in Retinal Disease The endoplasmic reticulum ER stress and UPR signaling Binding protein/glucose-regulated protein 78 PERK IRE1 ATF6 ER-associated degradation Apoptosis-inducing pathways Retinal diseases associated with ER stress Retinitis pigmentosa and other photoreceptor dystrophies Rhodopsin mutations cGMP-PDE mutations Carbonic anhydrase mutations LRAT mutations Diabetic retinopathy Macular degeneration Early-onset macular dystrophies Age-related macular degeneration References 24 Cell Death, Apoptosis, and Autophagy in Retinal Injury Introduction Modes of cell death Apoptosis Necrosis Other Cross-talk between cell death pathways Is cell death a bad thing? Autophagy and cell maintenance AGE-related retinal cell loss Retinal damage: death and repair Introduction Glaucoma and ganglion cell loss Diabetic retinopathy Macular degeneration Retinal detachment Retinal dystrophies Light damage Therapeutic options Neuroprotection Modulating autophagy Cellular replacement Conclusions References 25 Inflammatory Response and Mediators in Retinal Injury Introduction Retinal injury Ischemia–hypoxia Oxidative stress Oxidative stress and inflammation in AMD Microglia and AMD Other inflammatory-related molecules and pathways Genes and inflammation in AMD Oxidative stress and inflammation in retinopathy of prematurity Anti-inflammatory and antioxidant therapies in AMD and ROP Trauma Conclusion References 26 Basic Mechanisms of Pathological Retinal and Choroidal Angiogenesis Introduction Pathogenesis CNV associated with AMD (Fig. 26.3) Aging and senescence of the RPE Drusen, basal laminar/linear deposit formation Enzymatic and mechanical disruption of Bruch’s membrane Complement, AMD, and CNV Inflammation, bone marrow-derived cells, and CNV CNV membrane formation Cicatricial membrane formation Neovascularization associated with diabetic retinopathy Neovascularization associated with retinopathy of prematurity Neovascularization in vascular occlusions Neovascularization in uveitis Genetic aspects of neovascularization Age-related macular degeneration Diabetic retinopathy Retinopathy of prematurity Environmental factors Age-related macular degeneration Diabetic retinopathy Retinopathy of prematurity Angiogenic and antiangiogenic factors in neovacularization Vascular endothelial growth factor Insulin-like growth factor-1 Fibroblast growth factor-2 Integrins Ang and Tie2 Pigment epithelium-derived factor Matrix metalloproteinases Angiostatin and endostatin Advanced glycosolation end products Other growth factors Conclusions References 27 Blood–Retinal Barrier, Immune Privilege, and Autoimmunity Introduction Basic concepts of immunology Innate immunity Adaptive immunity Immune regulation Blood–ocular barrier Blood–retinal barrier in diabetic retinopathy Blood–retinal barrier in cystoid macular edema The eye as an immune-privileged site Transportation of antigens Downregulatory immune environment Downregulatory immune environment in age-related macular degeneration Anterior-chamber-associated immune deviation Retinal antigens and experimental autoimmune uveoretinitis S-antigen Interphotoreceptor retinoid-binding protein Rhodopsin Recoverin Phosducin Retinal autoimmunity Autoimmunity in human uveitis Role of retinal autoimmunity in protection Role of retinal autoimmunity in infection Conclusion References 28 Mechanisms of Macular Edema and Therapeutic Approaches Introduction Macular edema as A result of various disease mechanisms Causes of macular edema Molecular and cellular alterations leading to macular edema Cell-to-cell junctions and vascular permeability Inflammation and vascular permeability Growth factors, vasoactive factors, and vascular permeability Endothelial cell death and vascular permeability Extracellular matrix alterations and vascular permeability Transcellular transport and vascular permeability Neuronal involvement in the formation of macular edema Mechanical factors involved in the formation of macular edema Treatment of macular edema Laser treatment Medical treatment General aspects of systemic and topical medical therapy Carbonic anhydrase inhibitors and nonsteroidal anti-inflammatory drugs Nonsteroidal anti-inflammatory drugs (NSAIDs) Corticosteroids Antiangiogenic treatment Anti-VEGF agents Other medical treatments Surgical approaches Tractional origin of macular edema and surgical aspects Discussion and conclusion References 29 Cellular Effects of Detachment and Reattachment on the Neural Retina and the Retinal Pigment Epithelium Introduction Use and limitations of animal models in the study of retinal detachment Cellular changes in response to retinal detachment Acute retinal detachment RPE–photoreceptor interface Photoreceptors Second-order neurons and nonneuronal cell types Chronic retinal detachment and proliferative vitreoretinopathy Photoreceptors Second-order neurons and nonneuronal cell types Retinal reattachment References 30 Pathogenesis of Serous Detachment of the Retina and Pigment Epithelium Anatomic constituents Blood–retinal barrier Bruch’s membrane The choriocapillaris Mechanism of normal attachment Mechanical factors Adhesion Pressure gradient Metabolic factors Oxygenation Water movement Mechanisms of impairment Impairment of water movement Occurrence of detachment Persistence and resorption of serous detachments Clinical manifestations of PED and serous retinal detachments Serous retinal detachment associated with choroidal dysregulation Central serous chorioretinopathy Age-related macular degeneration Serous retinal detachment in idiopathic polypoidal choroidal vasculopathy Serous retinal detachment in uveitis: exudative retinal detachment Detachment of retinal origin Serous retinal detachment in diabetic retinopathy Severe retinal detachment in central or branch retinal vein occlusion Other causes Conclusion References Section 3: Genetics 31 Genetic Mechanisms of Retinal Disease Introduction Basic concepts in human genetics Inheritance Autosomal dominant inheritance Autosomal recessive inheritance X-linked or sex-linked inheritance Isolated cases Digenic and polygenic inheritance Chromosomes DNA, RNA, and proteins Gene structure Mitosis, meiosis, and linkage Evolution The human genome Overview Polymorphisms Single-nucleotide polymorphisms Short tandem repeats Other polymorphisms Mutations Genetic testing methods Informed clinical examination Screening known genes and mutations Linkage and homozygosity mapping High-throughput DNA sequencing Future prospects References 32 Mitochondrial Genetics of Retinal Disease Mitochondrial origins Mitochondrial structure Mitochondrial DNA Mitochondrial function Electron leakage and ROS formation Localization of mitochondria within the retina and optic nerve Influences of mtdna ON cell function Ancient inherited mtDNA variants representing populations (haplogroups) Definition of haplogroups Association of haplogroups with AMD and other eye diseases Recent maternally transmitted mtDNA mutations associated with retinal diseases Somatic mtDNA variations associated with retinal diseases Mechanisms of mtDNA damage mtDNA damage and AMD References 33 Epigenetic Mechanisms of Retinal Disease Brief history Concept DNA methylation Histone methylation Histone acetylation and deacetylation Noncoding RNA Epigenetic factors in the retina DNA methylation in mammalian retina Histone methylation and acetylation in mammalian retina miRNA in mammalian retina Epigenetic mechanisms in retinal development DNA and histone methylation in retinal development Histone acetylation in retinal development Chromatin remodeling complexes in retinal development microRNAs in retinal development Epigenetic mechanisms in retinal diseases Epigenetic factors in retinal fibrosis DNA methylation Histone acetylation/deacetylation Epigenetic factors in retinitis pigmentosa and other retinal degenerations Epigenetic factors in age-related macular degeneration Epigenetic factors in glaucoma Epigenetic factors in retinoblastoma Epigenetic factors in uveal melanomas Epigenetic factors in retinal angiogenesis Diabetic retinopathy Choroidal neovascularization Perspectives and challenges of epigenetics Treatment of retinal disease with epigenetic-modifying drugs References Section 4: Translational Basic Science 34 Gene Therapy for Retinal Disease Background: preclinical gene therapy studies Definitions Nonviral gene delivery Viral vector-mediated gene delivery Surgical delivery History of retinal gene therapy Preclinical studies: retinal transduction characteristics of different vectors Evaluation of different vectors Proof-of-concept studies Current status of retinal gene therapy trials: retinal diseases that have been/ARE currently being evaluated in human clinical trials Studies that were completed, but discontinued Retinoblastoma CNV using Ad.PEDF Studies in progress Encapsulated cell therapy Gene augmentation therapy for Leber congenital amaurosis CNV and AAV-sFLT CNV and lentivirus-mediated delivery of angiostatin and endostatin Promises and challenges of bringing retinal gene transfer from bench to bedside Safety/efficacy/stability Issues Outcome measures in human clinical trials Window of opportunity Plasticity of the visual system Genotyping issues Generic strategies for reversing blindness in “dead” retinas Conclusion State of the art of retinal gene therapy References 35 Stem Cells and Cellular Therapy Stem cells as therapeutics to treat retinal disease Definitions Embryonic stem cells Induced pluripotent stem cells Adult tissue stem cells Retinal stem and müller/glial cells Differentiation of HESC into photoreceptors Differentiation of HESC into three-dimensional embryonic and retinal tissues Retinal pigmented epithelial stem cells RPE cell-based delivery of trophic (and other) factors Embryonic stem cells as a source of RPE Differentiation of HESC into RPE Characterization of HESC-derived RPE in vitro Efficacy of HESC-derived RPE cells in vivo The use of induced pluripotent stem cells as a source of autologous RPE (and other cell type) grafts Potential problems associated with the use of iPSC to generate RPE grafts Synthetic small molecules to enhance iPSC and RPE production Adult bone marrow-derived endothelial progenitor cells Adult bone marrow contains a population of endothelial progenitor (stem) cells Bone marrow-derived EPC can contribute to retinal and choroidal neovascularization Bone marrow-derived EPC can exert a vasculotrophic rescue Bone marrow-derived EPC can exert a neurotrophic rescue in retinal degeneration Cord blood-derived stem cells Human clinical trials using stem cells for the treatment of retinal diseases Concluding remarks Acknowledgments References 36 Nanomedicine in Ophthalmology General principles of nanotechnology and nanomedicine Nanotechnology Nanomedicine Properties of nanomachines Physical properties Manufacture Applications to ophthalmology Delivery of drugs, peptides, and genes General considerations regarding nanoparticles Antibiotic therapy Antimetabolite therapy Neurotrophic factor therapy Antioxidant therapy Immune-suppressive therapy Gene therapy Nonviral vectors Viral vectors Ocular applications Imaging Minimally invasive physiological monitoring Coupling diagnostics and therapeutics Theranostics Prosthetics: molecules as machines (e.g., light-sensitive ion channels), abiotic–biotic interfaces Induced photosensitivity Bionic retina Regenerative medicine: nanostructured scaffolds to control cell phenotype Engineering scaffolds to support cell transplants Scaffolds for cell transplantation to the subretinal space Surgical technology Obstacles to incorporation of nanotechnology into ophthalmology Persistence of nanoparticles despite immune surveillance Safe manufacturing techniques Cell-by-cell dose delivery and control Unintended biological consequences Conclusion References 37 Neuroprotection History and definitions Retinal ganglion cell glaucomatous disease Neurotrophic factors in glaucoma Neuroprotection through the serotonin pathway Neurotrophic factors for retinitis pigmentosa CNTF protein and historical selection CNTF phase I trial for human photoreceptor degeneration New technology for endpoints for photoreceptor degenerations Delivery of neurotrophins Antioxidants Oxidative damage in light-induced and inherited photoreceptor degenerations Preclinical evidence of antioxidant protection in photoreceptor degenerations Inhibitors of NADPH oxidase (Nox) Nitric oxide synthase (NOS) inhibitors Bolstering the endogenous antioxidant defense system Carotenoids (lutein, zeaxanthin) in combination with other antioxidants Rac1 Rod-derived cone viability factor N-acetylcysteine Saffron (Crocus sativus extract) Nanoceria Clinical evidence of antioxidant protection in photoreceptor degenerations Age-related eye disease study (AREDS) Controlled clinical studies on antioxidants in AMD and RP employing visual function endpoints Carotenoids alone or in combination with other antioxidants Age-related macular degeneration Retinitis pigmentosa Other antioxidants Neuroprotection with small molecules Neuromodulators/neurotransmitters Calcium channel blockers Retinoids Modulation of intracellular neurotrophic pathways Heat shock proteins Minocycline Rho GTPases Long-chain polyunsaturated fatty acids Peptide neurotrophin receptor agonists/antagonists References 38 Drug Delivery Introduction A brief history of the field of drug delivery Drug delivery Formulating sustained-delivery systems Delivering drugs in a targeted manner The role of devices in drug delivery Gene delivery Viral systems Nonviral systems Cellular delivery for sustained drug delivery Engineering cells for delivery Engineering materials for immunological protection Routes of delivery to the retina Traditional routes of administration Oral delivery Topical delivery Injections Novel approaches for administration Devices Inserts MEMs devices Replenish external scleral fixated refillable device Ionophoresis system Implants Vitrasert ganciclovir implant Retisert fluocinolone implant Iluvien fluocinolone implant Ozurdex dexamethasone implant I-vation triamcinolone implant Encapsulated cell technology (ECT) ciliary neurotropic factor (CNTF) implant ECT technology anti-VEGF implant Injectables Micro- and nanoparticles Nanoscale systems Ocular uptake of systemically delivered nanoparticles Nanocomposites for topical delivery Pharmacokinetics in the eye Barriers to delivery Modeling delivery Impact of drug chemistry Impact of depot placement References 39 Retinal Laser Therapy: Biophysical Basis and Applications Introduction Optical properties of the eye Basics of lasers Laser beam delivery to tissue Aberrations Contact lenses Interactions of light with tissue Photochemical interactions Clinical indication: photodynamic therapy for subfoveal choroidal neovascularization Photothermal interactions Sublethal thermotherapy Necrosis Transpupillary thermotherapy Photocoagulation Healing of retinal lesions Pattern-scanning laser photocoagulation Clinical indications: treatment of diabetic retinopathy Age-related macular degeneration: extrafoveal neovascular lesions Selection of optimal wavelengths for coagulation Photodisruption Selective retina therapy (SRT) Future developments Monitoring retinal temperature Optical monitoring of tissue changes in real time References VOLUME 2 Section 1: Retinal Degenerations and Dystrophies 40 Retinitis Pigmentosa and Allied Disorders Early history Typical retinitis pigmentosa Clinical features Nyctalopia Visual field loss Central vision loss Color vision defects Photopsia and other symptoms Fundus appearance Vitreous abnormalities Anterior-segment abnormalities Refractive status Psychophysical findings Perimetry Dark adaptometry Retinal densitometry (fundus reflectometry) Electrophysiology Imaging modalities in RP Fundus photography/fluorescein angiography Autofluorescence Optical coherence tomography Adaptive optics scanning laser ophthalmoscopy Classification Subdivision by inheritance type Subdivision by age of onset Subdivision by molecular defect Subdivision by distribution of retinal involvement or fundus appearance Sector and sectoral retinitis pigmentosa Pericentral retinitis pigmentosa Unilateral or extremely asymmetrical retinitis pigmentosa Complicated retinitis pigmentosa Systemic associations Usher syndrome Differential diagnosis – phenocopies of retinitis pigmentosa Cone–rod and cone dystrophy Leber congenital amaurosis/severe early childhood onset retinal dystrophy (SECORD) Bardet–Biedl syndrome Refsum syndromes Infantile Refsum disease Adult-onset Refsum disease Neuronal ceroid lipofuscinosis (Batten’s disease) Differential diagnosis: pseudoretinitis pigmentosa Retinal inflammatory diseases Rubella retinopathy Syphilis Infectious retinitis Autoimmune paraneoplastic retinopathy Drug toxicity (see Chapter 89, Drug toxicity) Thioridazine Chlorpromazine Chloroquine Hydroxychloroquine Quinine Pigmented paravenous retinochoroidal atrophy Traumatic retinopathy Diffuse unilateral subacute neuroretinitis Grouped pigmentation of the retina Basic science Molecular biology Molecular genetics Autosomal dominant RP genes Autosomal recessive RP genes X-linked RP genes Digenic inheritance and RP Usher syndrome molecular genetics Protein chemistry Abnormal pre-mRNA splicing RPGR interactome Ush interactome Bardet–Biedl syndrome and the “BBSome” Abnormal intracellular trafficking Cell death pathways Cell and tissue biology Histopathology Photoreceptor abnormalities Outer retinal disease Inner retinal pathology Cellular remodeling and vascular changes Genetic consultation Counseling family groups Support services Treatment Cataract extraction Macular edema Vitamin A supplements Docosahexaenoic acid supplements Lutein supplements Clinical trial of DHA supplementation Clinical trials of lutein supplementation Purported “cures” for RP Future management Gene therapy Cell therapy (see Chapter 35, Stem cells and cellular therapy, and Chapter 125, Transplantation frontiers) Apoptosis/neuroprotection Electronic prosthesis (artificial retina) Acknowledgment References 41 Hereditary Vitreoretinal Degenerations Snowflake vitreoretinal degeneration General features Clinical findings Ocular features Molecular genetics of SVD Visual psychophysics Electrophysiology Differential diagnosis Stickler syndrome type I Stickler syndrome type II Marshall syndrome Wagner syndrome Goldmann–Favre vitreotapetoretinal degeneration Management The chromosome 5Q retinopathies: wagner syndrome, jansen syndrome, erosive vitreoretinopathy, and related conditions General features Clinical findings Ocular features Visual psychophysics Electrophysiology Differential diagnosis Autosomal dominant vitreoretinopathies Snowflake vitreoretinal degeneration Stickler syndrome Autosomal dominant vitreoretinochoroidopathy Autosomal recessive vitreoretinopathies Goldmann–Favre syndrome (GFS) and enhanced S-cone syndrome Knobloch syndrome Management Genetic counseling Treatments Chondrodysplasias associated with vitreoretinal degeneration: the stickler syndromes, marshall syndrome, kniest dysplasia, knobloch syndrome, and weissenbacher–zweymuller syndrome General features Clinical findings Extraocular features Ocular features Differential diagnosis Marfan syndrome Wagner syndrome Erosive vitroeretinopathy Management X-linked retinoschisis General features Clinical findings Ocular features Visual psychophysics Optical coherence tomography Electrophysiology Differential diagnosis Management Genetic counseling Treatment Pharmacological treatment Laser Surgery Gene therapy Retina and/or progenitor cell transplantation Retinal nuclear receptor (NR2E3)-related diseases: enhanced S-cone syndrome and goldmann–favre vitreotapetoretinal degeneration General features Clinical findings Ocular features Visual psychophysics Electrophysiology Differential diagnosis X-linked retinoschisis Cystoid macular edema Management Other vitreoretinal degenerations and vitreoretinopathies Autosomal dominant vitreoretinochoroidopathy Autosomal recessive inherited vitreoretinal dystrophy Hereditary neovascular vitreoretinopathies Autosomal dominant neovascular inflammatory vitreoretinopathy Dominantly inherited peripheral retinal neovascularization References 42 Macular Dystrophies Introduction The initial approach to a patient with macular dystrophy Best macular dystrophy Clinical features of BMD Visual function Refractive error Optical coherence tomography (OCT) Fluorescein angiography and autofluorescence Electrophysiology Genetics Pathophysiology and histopathology Additional phenotypes associated with mutations in BEST1 Autosomal dominant vitreoretinochoroidopathy (ADVIRC) Autosomal recessive bestrophinopathy (ARB) Treatment Stargardt disease Clinical features of Stargardt disease Visual function Fluorescein angiography and autofluorescence Optical coherence tomography Electrophysiology Genetics Pathophysiology and histopathology Treatment Stargardt-like dominant macular dystrophy (SLDMD) Pathophysiology Pattern dystrophy Clinical features and history of specific pattern dystrophies Butterfly-shaped pigment dystrophy Adult-onset foveomacular vitelliform pattern dystrophy Sj?gren reticular dystrophy of the RPE Central areolar choroidal dystrophy (central areolar retinochoroidal dystrophy) Electrophysiology Pathophysiology Treatment Sorsby fundus dystrophy Clinical features of SFD Genetics Pathophysiology Treatment Autosomal dominant radial drusen (doyne honeycomb retinal dystrophy, malattia leventinese) Clinical features of ADRD Visual function and electrophysiology Imaging Pathophysiology and histopathology Treatment North carolina macular dystrophy Spotted cystic dystrophy Dominant cystoid macular dystrophy Fenestrated sheen macular dystrophy (FSMD) Glomerulonephritis type II and drusen Acknowledgments References 43 Hereditary Choroidal Diseases Introduction Choroidal atrophy phenotypes Central areolar choroidal dystrophy Peripapillary choroidal dystrophy Diffuse choroidal dystrophy Gyrate atrophy of the choroid and retina Choroideremia Clinical phenotypes resembling hereditary choroidal diseases X-linked retinitis pigmentosa (XLRP) Kearns–Sayre syndrome (KSS) Bietti’s crystalline dystrophy Thioridazine (Mellaril) retinal toxicity Stargardt disease Pattern macular dystrophy Conclusion References 44 Abnormalities of Cone and Rod Function Disorders of the cone system Achromatopsia Diagnosis Molecular basis of achromatopsia Treatment Cone monochromatism and blue cone monochromatism Diagnosis Molecular basis of blue cone monochromatism Treatment Progressive cone dystrophies Diagnosis Molecular basis of cone–rod dystrophies Treatment Congenital stationary night blindness CSNB with normal fundi Diagnosis Molecular basis of CSNB CSNB with abnormal fundi Oguchi disease Diagnosis Molecular basis of Oguchi disease Fundus albipunctatus Diagnosis Molecular basis of fundus albipunctatus Treatment for CSNB References Section 2: Retinal Vascular Disease 45 The Epidemiology of Diabetic Retinopathy Introduction Prevalence of diabetic retinopathy Incidence and progression of diabetic retinopathy and incidence of clinically significant macular edema The relationship of race/ethnicity to diabetic retinopathy Genetic factors Sex Age and puberty Duration of diabetes Age at diagnosis Glycemia C-peptide status Exogenous insulin Blood pressure Proteinuria and diabetic nephropathy Serum lipids and lipid lowering Smoking Alcohol Body mass index (BMI) Physical activity Socioeconomic status Hormone and reproductive exposures in women Comorbidity and mortality New medical interventions Public health applications of epidemiological data Conclusion References 46 Diabetic Retinopathy: Genetics and Etiologic Mechanisms Introduction Anatomic lesions Loss of pericytes Capillary basement membrane thickening Microaneurysms Capillary acellularity Breakdown of blood–retina barrier Biochemical mechanisms in the pathogenesis of diabetic retinopathy The aldose reductase theory Advanced glycation endproduct (AGE) theory Reactive oxygen intermediates (ROI) theory Protein kinase C (PKC) theory Insulin receptors and glucose transporters Genetic factors in the pathogenesis of diabetic retinopathy Other ocular factors Retinopathy in different forms of diabetes Animal models in the study of diabetic retinopathy Cell culture studies Conclusion Acknowledgments References 47 Nonproliferative Diabetic Retinopathy and Diabetic Macular Edema Natural course of nonproliferative diabetic retinopathy Diabetes mellitus without retinopathy Microaneurysms Retinal vascular hyperpermeability Diabetic macular edema Capillary closure, microvascular remodeling, and retinal ischemia Alterations of the vitreous gel and vitreoretinal interface Clinical evaluation of nonproliferative diabetic retinopathy Duration of diabetes mellitus Hyperglycemia Hypertension Dyslipidemia Other extraocular factors Ophthalmic evaluation Ancillary ocular imaging Fundus photography Fluorescein angiography Optical coherence tomography Funduscopic lesions of nonproliferative diabetic retinopathy Classification of diabetic retinopathy Clinical evaluation of diabetic macular edema Distribution of retinal thickening and hard exudates Magnitude of retinal thickening Retinal microvascular alterations and vascular hyperpermeability Traction by vitreous gel and epiretinal proliferation Alterations in the retinal pigment epithelium Subretinal fibrosis Visual acuity and its correlation to retinal thickening and fluorescein leakage Diurnal variation of DME Management of nonproliferative diabetic retinopathy and diabetic macular edema Modification of systemic risk factors Retinopathy screening and surveillance Ocular treatment for diabetic macular edema Focal/grid laser photocoagulation Pharmacotherapy with vascular endothelial growth factor (VEGF) antagonists Pharmacotherapy with corticosteroids Vitrectomy Ocular treatment for nonproliferative diabetic retinopathy Other systemic treatment for nonproliferative diabetic retinopathy Conclusion References 48 Proliferative Diabetic Retinopathy Pathogenesis of proliferative diabetic retinopathy Origin and early recognition of preretinal new vessels Natural course of proliferative diabetic retinopathy Development and proliferation of new vessels Contraction of the vitreous and fibrovascular proliferation Retinal distortion and tractional detachment Involutional or “Quiescent” Proliferative Diabetic Retinopathy Relationship of proliferative diabetic retinopathy to type and duration of diabetes Proliferative diabetic retinopathy and blood glucose control Early worsening of retinopathy with improved glycemic control Absence of proliferative diabetic retinopathy in individuals with diabetes of extreme duration Systemic medications and proliferative diabetic retinopathy Other risk factors for proliferative diabetic retinopathy Management of proliferative diabetic retinopathy Pituitary ablation Early laser trials Panretinal photocoagulation Early treatment diabetic retinopathy study and the timing of treatment Scatter photocoagulation and macular edema Panretinal photocoagulation and advanced proliferative diabetic retinopathy Current techniques of panretinal photocoagulation Direct (local) treatment of NVE Distribution and strength of panretinal photocoagulation Pattern scanning laser delivery systems Number of episodes used for scatter treatment Wavelength Regression of new vessels after initial photocoagulation and indications for retreatment Complications of prp Antiangiogenic therapies for proliferative diabetic retinopathy Pharmaceutical vitreolysis for treatment of pdr Indications for vitrectomy Conclusion References 49 Hypertension Introduction Hypertensive retinopathy Definition and classification Epidemiology Relationship with stroke Relationship with coronary heart disease Relationship with other end-organ damage of hypertension Hypertensive choroidopathy Hypertensive optic neuropathy Future directions Conclusion References 50 Telescreening for Diabetic Retinopathy Introduction Guidelines for telescreening program American Telemedicine Association telehealth practice recommendations for diabetic retinopathy Steps of telescreening Technical considerations Image acquisition Compression Data transfer, archiving, and retrieval Security and documentation Operational considerations Detection of diabetic retinopathy and macular edema Role of the reading center to grade retinal images Pathways of grading Pathway 1: Disease/no disease grading Pathway 2: Full disease grading Arbitration grade Reading personnel Handling of ungradable images Quality assurance Evaluating telescreening programs Efficacy Patient satisfaction Cost-effectiveness Advances in telescreening Automated retinal image analysis Conclusion References 51 Retinal Artery Obstructions Central retinal artery obstruction Epidemiology Clinical features Ancillary studies Systemic associations Evaluation Treatment Branch retinal artery occlusion Cilioretinal artery occlusion Combined retinal artery and vein occlusion Cotton-wool spots References 52 Acquired Retinal Macroaneurysms Clinical description Diagnosis of retinal macroaneurysm Natural course and treatment of retinal macroaneurysms References 53 Branch Vein Occlusion Introduction Pathogenesis Clinical features Symptoms Signs Complications Clinical evaluation Clinical examination Fluorescein angiography Wide-field angiography Optical coherence tomography Diagnostic workup Young patient Older patient Bilateral or numerous BRVO patients Treatment options Medical treatment Laser treatment Branch Vein Occlusion Study for macular edema Branch Vein Occlusion Study for neovascularization Steroid treatment SCORE (triamcinolone) study GENEVA (dexamethasone implant) study Anti-VEGF treatment BRAVO (ranibizumab) study Other anti-VEGF inhibitors Bevacizumab Pegaptanib Aflibercept Experimental treatments FAVOR (iluvien) study Surgical management Vitrectomy with or without sheathotomy Follow-up Conclusions Disclosure References 54 Central Retinal Vein Occlusion Clinical features Perfusion status Pathogenesis Risk factors and associations Clinical evaluation Therapeutic options Treatment of macular edema Observation Corticosteroid therapy Intravitreal anti-VEGF therapy Treatment of ocular neovascularization Laser photocoagulation Medical therapy Treatment of systemic medical conditions Alternative treatments Chorioretinal venous anastomosis Tissue plasminogen activator Surgical treatments Vitrectomy Radial optic neurotomy Follow-up Conclusion References 55 Macular Telangiectasia Introduction History, nomenclature, and classification of macular telangiectasia Classification Yannuzzi classification Epidemiology Prevalence of disease: estimates from population-based studies Beaver dam eye study Melbourne collaborative cohort study Clinical presentation Fundus appearance Retinal imaging Fundus autofluorescence Fluorescein angiography Optical coherence tomography Adaptive optics imaging Visual function Microperimetry Staging and prognostic factors Genetics Association of systemic diseases Differential diagnosis Clinicopathological correlation Therapeutic options Summary and future research directions References 56 Coats Disease History Histopathology, etiology, and pathogenesis Clinical presentation Diagnostic testing Fluorescein angiography Computed tomography Magnetic resonance imaging Doppler ultrasonography Blood testing Differential diagnosis Treatment Ablative therapies – laser photocoagulation and cryotherapy Pharmacologic therapies Surgery Outcomes References 57 Hemoglobinopathies Prevalence Genetic modifiers Pathophysiology Systemic manifestations Ophthalmic clinical features Retrobulbar and orbital involvement Anterior-segment involvement Posterior-segment involvement Vitreoretinal interface Optic nerve Macula Angioid streaks Retinal vasculature Nonproliferative sickle retinopathy Salmon patch hemorrhages Iridescent spots Black sunburst Proliferative sickle retinopathy Goldberg stages Stage I Stage II Stage III Stage IV Stage V Alternative classification schemes Incidence/prevalence Risk factors Natural history Ophthalmic treatments Imaging Potential therapeutic options for the future References 58 Radiation Retinopathy Introduction Etiology, pathogenesis, and histopathology Natural history and clinical features Classification Risk factors Incidence and dosimetry Radiation type Treatment modality Total radiation dose Fractionation schedule Volume of retina irradiated Total elapsed time Differential diagnosis and diagnostic evaluation Prevention and treatment Prognosis Conclusion References 59 Ocular Ischemic Syndrome Demographics and incidence Etiology Clinical presentation Visual loss Prolonged light recovery Scintillating scotomas Amaurosis fugax Pain Visual acuity External collaterals Anterior segment changes Posterior segment findings Ancillary studies Fluorescein angiography Electroretinography Carotid artery imaging Others Systemic associations Differential diagnosis Treatment Total carotid artery obstruction Less than total carotid artery obstruction Carotid endarterectomy in general Medical therapy Direct ocular therapeutic modalities References 60 Coagulopathies General considerations Disseminated intravascular coagulation Idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura HELLP syndrome Ophthalmic involvement Conclusion References 61 Pediatric Retinal Vascular Diseases Retinopathy of prematurity Historical perspective Early history Retinopathy of prematurity and contemporary nursery practices The role of oxygen Clinical findings Experimental findings Mechanism of oxygen’s effects on the immature retina Primary stage of retinal vasoconstriction and vascular occlusion Secondary stage of retinal neovascularization Pathogenesis Normal retinal vasculogenesis Pathogenesis of ROP International classification Zones of involved retina Extent of retinopathy of prematurity Staging Stage 1: demarcation line Stage 2: ridge Stage 3: ridge with extraretinal fibrovascular proliferation “Plus” and “pre-plus” disease Zone I ROP Aggressive posterior ROP Classification of retinal detachment Stage 4A: extrafoveal retinal detachment Stage 4B: partial retinal detachment including the fovea Stage 5: total retinal detachment Other factors related to retinal detachment Involution of retinopathy of prematurity Regressed rop: retinal detachment, strabismus, and amblyopia History of prematurity Ocular findings of regressed retinopathy of prematurity Myopia Other refractive and binocular defects Lens and corneal changes Glaucoma in retinopathy of prematurity Glaucoma in patients with advanced retinopathy Angle closure glaucoma in regressed retinopathy of prematurity Differential diagnosis Risk factors Examination procedures in the nursery General aspects and timing of the examination Screening guidelines Side-effects of the examination Techniques of eye examination Informing the patient’s family Prophylaxis and therapy The role of vitamin E The role of light Cryotherapy The multicenter trial of cryotherapy Treatment Results Current concepts in management of retinopathy of prematurity Treatment techniques Cryotherapy – special considerations Laser – special considerations The Early Treatment for Retinopathy of Prematurity trial Retinal detachment The ETROP study: better outcomes, changing clinical strategy Anti-VEGF therapy for posterior ROP Other pediatric retinal vascular diseases Coats disease Persistent fetal vasculature Incontinentia pigmenti Familial exudative vitreoretinopathy and Norrie disease References 62 Telescreening for Retinopathy of Prematurity Limitations of traditional care Telemedicine as an emerging approach Evaluation studies Accuracy Image quality Cost-effectiveness, speed, and satisfaction Evaluation of operational ROP telemedicine programs Barriers and challenges Future directions Disclosure References Section 3: Choroidal Vascular/Bruch\'s Membrane Disease 63 Epidemiology and Risk Factors for Age-Related Macular Degeneration Classification Prevalence Incidence Quality of life Sociodemographic risk factors Age Gender Race/ethnicity Socioeconomic status Ocular risk factors Refractive error Iris color Lens opacities, cataracts, and cataract surgery Cup-to-disc ratio Behavioral and lifestyle factors Smoking Antioxidants, vitamins, and minerals Alcohol intake Obesity and physical activity Sunlight exposure Medications Cardiovascular-related factors Cardiovascular diseases Blood pressure and hypertension Cholesterol levels and dietary fat intake Diabetes and hyperglycemia Hormonal and reproductive factors Inflammatory factors Genetic factors Conclusion References 64 Pathogenetic Mechanisms in Age-Related Macular Degeneration Introduction Structural changes Choroid Therapeutic implications Bruch’s membrane Therapeutic implications The retinal pigment epithelium Therapeutic implications Outer retina Therapeutic implications Conclusion References 65 Age-Related Macular Degeneration: Non-neovascular Early AMD, Intermediate AMD, and Geographic Atrophy Introduction Aging The aging eye – clinical findings The aging eye – morphologic changes Photoreceptors Retinal pigment epithelium Bruch’s membrane Changes in hydraulic conductivity Choroid Onset and progress of age-related macular degeneration Clinical features in the absence of drusen Morphologic changes Basal laminar deposit – early form Membranous debris Internal to the retinal pigment epithelium basement membrane External to the RPE basement membrane (basal linear deposit )* At the apex of the retinal pigment epithelium Basal laminar deposit – late form (diffuse thickening of the internal aspect of Bruch’s membrane) Retinal pigment epithelium and photoreceptors Bruch’s membrane and choroid Drusen Clinical grading Drusen type Drusen size Extent of fundus involvement Drusen distribution Drusen symmetry Drusen color Clinical grading of AMD severity Grading in scientific studies Imaging of drusen Fluorescence of drusen Autofluorescence Ocular coherence tomography (OCT) Pathologic considerations Clinicopathologic classification Small, hard (hyalinized, nodular) drusen Clinical features Formation Significance Soft (pseudosoft) cluster-derived drusen True soft drusen Granular soft drusen (synonyms: serogranular drusen, semisolid drusen, localized detachment of the basal linear deposit) Soft, fluid (serous) drusen and drusenoid pigment epithelial detachments Disappearance of drusen following prophylactic laser photocoagulation Soft (membranous) drusen (localized accumulation of the basal linear deposit) Reticular pseudodrusen, reticular drusen, subretinal drusenoid deposits Regressing (fading) drusen (localized detachment of the basal laminar deposit within an area of retinal pigment epithelium and photoreceptor atrophy) Outcome of drusen Histochemistry Incipient atrophy (nongeographic atrophy) Pathology Choroidal perfusion in age-related macular degeneration Relationship to age-related macular degeneration Functional effects Prognostic value Geographic atrophy Evolution Drusen-unrelated atrophy Drusen-related atrophy Following pigment epithelial detachments Pathology Choroidal atrophy Imaging geographic atrophy Fluorescein angiography Fundus autofluorescence Optical coherence tomography Clinical significance of geographic atrophy Prognosis Geographic atrophy and choroidal neovascularization Intermediate stage of age-related macular degeneration and cataract Age-related macular degeneration and age Management of non-neovascular AMD References 66 Neovascular (Exudative or “Wet”) Age-Related Macular Degeneration Epidemiology Risk factors Clinical (including biomicroscopic) presentation Overview Retinal pigment epithelial detachments Breakthrough vitreous hemorrhage Massive subretinal hemorrhage Retinal pigment epithelial tears Disciform scars Fluorescein angiographic features Overview Classic choroidal neovascularization Occult choroidal neovascularization Other terms relevant to interpreting fluorescein angiography of choroidal neovascularization Retinal pigment epithelium detachments in age-related macular degeneration Other angiographic features Speckled hyperfluorescence Fading choroidal neovascularization Feeder vessels Retinal lesion anastomosis (“retinal angiomatous proliferans” or “chorioretinal anastomosis”) Loculated fluid Retinal pigment epithelial tears Disciform scars Pathogenesis Choroidal neovascularization Histopathology Associated factors Differential diagnosis Choroidal neovascularization Vitreous hemorrhage Natural history Well-defined extrafoveal and juxtafoveal choroidal neovascularization Subfoveal choroidal neovascularization Natural course of large subfoveal subretinal hemorrhage in age-related macular degeneration Retinal pigment epithelial tears Laser photocoagulation treatment Laser treatment of well-defined choroidal neovascular lesions Preparation for laser photocoagulation treatment Macular Photocoagulation Study photocoagulation techniques Evaluations following laser photocoagulation Complications of laser photocoagulation Photodynamic therapy Results of photodynamic therapy treatment Preparation for photodynamic therapy Follow-up after photodynamic therapy Pharmacologic therapy with anti-VEGF products and overall management approach to CNV in AMD Efficacy of ranibizumab vs PDT with verteporfin for predominantly classic subfoveal CNV lesions Efficacy of ranibizumab vs sham treatment for minimally classic or occult with no classic subfoveal choroidal neovascular lesions and presumed recent disease progression Safety of ranibizumab Impact of noninferiority results on frequency of treatment and the role of aflibercept or bevacizumab in place of ranibizumab Potential implications of anti-VEGF noninferiority trials results on clinical practice Follow-up after deciding to initiate anti-VEGF therapy for neovascular AMD Early identification of choroidal neovascularization Prevention of choroidal neovascularization Risk of fellow-eye involvement Additional therapies Submacular surgery Indocyanine green angiography Radiation therapy Other pharmacologic therapies and combination therapies Patient education and rehabilitation Disclosure References 67 Pharmacotherapy of Age-Related Macular Degeneration Introduction Etiologic factors Genetic susceptibility Environmental factors Diet Smoking* Light exposure Use of medications Systemic risk factors The pathophysiology of exudative amd: the crucial role of cytokines Definition and steps in angiogenesis VEGF and other positive and negative modulators of angiogenesis Vascular permeability VEGF receptors VEGFR-2 (KDR in humans or FLK-1 in mice) Other cytokines and regulators of angiogenesis Naturally occurring upregulators of angiogenesis Fibroblast growth factor and integrins Platelet-derived growth factor Angiopoietins Matrix metalloproteinases and tissue inhibitors of metalloproteinases Naturally occurring downregulators of angiogenesis Pigment epithelial-derived factor Other cytokines Agents currently in use or under investigation: non-neovascular AMD Antioxidants, vitamins, and cofactors Age-Related Eye Disease Study (AREDS) and related supplements Visual cycle inhibitors* Complement modulators* Agents currently in use or under investigation: neovascular AMD VEGF inhibitors Direct VEGF inhibitors Monoclonal antibody: bevacizumab (Avastin) Antigen binding fragment: ranibizumab (Lucentis) Comparison of Age-related Macular Degeneration Treatments Trial (CATT) Soluble receptor: aflibercept (VEGF-TRAP EYE) KH902 Adeno-associated viral vector (AAV) gene transduction Oligonucleotide aptamer (pegaptanib – Macugen) Small interfering RNA (siRNA) Intracellular signaling blockers PDGF/PDGFR inhibitors* TrpRS Protein kinase C inhibitors Complement inhibitors* Naturally occurring inhibitory polypeptides and inducible cleavage products Pigment epithelial-derived factor Pathologically expressed circulating molecules Angiostatin and endostatin Extracellular matrix modulators Integrin antagonists MMP inhibitors Other molecules Squalamine The role of steroids and other immunomodulators Steroids Rapamycin Photodynamic Therapy Pharmacology of photodynamic sensitizers Verteporfin (Visudyne) Combination therapies* Conclusion References 68 Myopic Macular Degeneration Epidemiology Pathogenesis Histopathology The sclera Choroid and retinal pigment epithelium Animal models Features of the myopic fundus Myopic conus Posterior staphyloma Myopic chorioretinal atrophy Lacquer cracks Myopic chorodial neovascularization Myopic macular retinoschisis or myopic foveoschisis Natural course and treatment of myopic CNV Conclusion References 69 Angioid Streaks Introduction Histopathology Systemic associations Ocular manifestations and clinical course Ocular imaging and diagnosis Fluorescein angiography (FA) Fundus autofluorescence (FAF) Indocyanine green angiography (ICGA) Spectral domain optical coherence tomography (SD-OCT) Therapy Laser photocoagulation Transpupillary thermotherapy Photodynamic therapy Macular translocation Anti-VEGF treatment Bevacizumab Ranibizumab Combination therapy Conclusion References 70 Ocular Histoplasmosis Historical perspective Clinical features of ocular histoplasmosis Differential diagnosis Relationship of ocular disease to systemic infection Clinical features of systemic infection Epidemiology of ocular histoplasmosis Geographic distribution of H. capsulatum in the USA Prevalence and incidence Age Gender and race Histocompatibility antigens and genetic predisposition Pathogenesis Natural history of ocular histoplasmosis and public health implications Treatment Laser photocoagulation Photodynamic therapy Anti-VEGF therapy Combination therapy Intravitreal triamcinolone Submacular surgery and macular translocation References 71 Polypoidal Choroidal Vasculopathy Introduction Pathogenesis Clinical features Demographics Clinical findings Angiographic features Classification Differential diagnosis Neovascular age-related macular degeneration Central serous chorioretinopathy Treatment Thermal laser photocoagulation Photodynamic therapy Anti-VEGF therapy Combination therapy References 72 Central Serous Chorioretinopathy Introduction Pathogenesis, predisposition, and risk factors Clinical features Demographics Symptoms Signs Investigations Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Multifocal electroretinography Microperimetry Natural history Differential diagnosis Optic disc pit Age-related macular degeneration Polypoidal choroidal vasculopathy Inflammatory and infectious diseases Autoimmune and vascular disorders Intraocular tumors Treatment Observation in most cases Treatment for selected cases Safety-enhanced photodynamic therapy in selected cases PDT with verteporfin Conventional PDT with normal dosage and fluence Safety-enhanced PDT with reduced verteporfin dosage Safety-enhanced PDT with reduced laser fluence Historical thermal (argon) laser photocoagulation and micropulsed diode laser Transpupillary thermotherapy Intravitreal anti-VEGF therapy with or without adjuvant PDT Anticorticosteroid treatment Management of special variants of CSC Bullous CSC and its putative management Other potential but still exploratory systemic therapies Systemic acetazolamide Antiadrenergic blockage and beta-blockers Aspirin, finasteride, anti-Helicobacter pylori treatment Conclusion References 73 Uveal Effusion Syndrome and Hypotony Maculopathy Uveal effusion syndrome Introduction Pathophysiology of ciliochoroidal effusions General mechanisms Idiopathic and nanophthalmic uveal effusion Clinical features Diagnostic studies Ophthalmic ultrasound Angiography and optical coherence tomography Differential diagnosis Congenital and acquired scleropathies Hydrodynamic effusions Inflammatory factors Neoplastic effusions Treatment of idiopathic uveal effusion syndrome Scleral thinning procedures Pars plana vitrectomy Vortex vein decompression Conclusion Hypotony maculopathy Introduction Clinical features Diagnosis Fluorescein angiography Ocular ultrasound Optical coherence tomography Pathogenesis Hypotony Decreased aqueous production Increased aqueous outflow Mechanism of maculopathy Mechanism of optic disc edema Differential diagnosis Idiopathic chorioretinal folds Retrobulbar mass lesions Scleral inflammation Scleral buckle Choroidal tumors Choroidal neovascularization Focal chorioretinal scars Optic nerve head disorders Retinal folds Treatment Conclusion References Section 4: Inflammatory Disease/Uveitis 74 Sympathetic Ophthalmia Introduction Epidemiology Pathogenesis Immunopathology Clinical findings Diagnosis Differential diagnosis Course and complications Therapy Prevention Prognosis References 75 Vogt–Koyanagi–Harada Disease Introduction and historical aspects Epidemiology Clinical description The prodromal stage The acute uveitic stage The chronic uveitic stage The chronic recurrent stage Frequency of distinguishing clinical features Pathology and pathogenesis Investigations Imaging studies Lumbar puncture Differential diagnosis Treatment Complications and management Prognosis Conclusion References 76 White Spot Syndromes and Related Diseases Introduction Birdshot chorioretinopathy Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Electroretinogram Electrooculogram Visual field testing Systemic associations Pathogenesis Differential diagnosis Management/treatment Immunosuppressive therapy Summary Placoid diseases Acute posterior multifocal placoid pigment epitheliopathy Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Systemic associations Pathogenesis Differential diagnosis Management/treatment Summary Serpiginous choroiditis Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Perimetry Systemic associations Pathogenesis Differential diagnosis Management/treatment Summary Relentless placoid chorioretinitis Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Systemic associations Pathogenesis Differential diagnosis Management/treatment Summary Persistent placoid maculopathy Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Systemic associations Pathogenesis Differential diagnosis Management/treatment Summary Multifocal choroiditis and panuveitis, punctate inner choroidopathy, and progressive subretinal fibrosis and uveitis syndrome Multifocal choroiditis and panuveitis Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology testing Visual field testing Systemic associations Punctate inner choroidopathy Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Electrophysiology Visual field testing Pathogenesis Differential diagnosis Differentiation of MFC and POHS Differentiation of MFC and PIC Management/treatment Progressive subretinal fibrosis and uveitis syndrome Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Electrophysiology Systemic associations Pathogenesis Differential diagnosis Management/treatment Summary Multiple evanescent white dot syndrome, acute zonal occult outer retinopathy, acute idiopathic blind spot enlargement, and acute macular neuroretinopathy Multiple evanescent white dot syndrome Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Visual field testing Pathogenesis Differential diagnosis Management/treatment Summary Acute zonal occult outer retinopathy Clinical course Clinical symptoms Epidemiology Fundus findings Other ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Fundus autofluorescence Optical coherence tomography Visual field testing Electrophysiology Association with ocular systemic diseases Pathogenesis Differential diagnosis Management/treatment Summary Acute idiopathic blind spot enlargement Clinical course Clinical symptoms Epidemiology Fundus findings Ocular findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Electrophysiology Visual field testing Pathogenesis Differential diagnosis Management/treatment Summary Acute macular neuroretinopathy Clinical course Clinical symptoms Epidemiology Fundus findings Clinical course and prognosis Imaging Fluorescein angiography Indocyanine green angiography Optical coherence tomography Fundus autofluorescence Electrophysiology Visual fields Systemic associations Pathogenesis Differential diagnosis Management/treatment Summary Acknowledgment References 77 Autoimmune Retinopathies Introduction Epidemiology and mechanisms Clinical features Diagnosis Differential diagnosis Treatment and prognosis References 78 Sarcoidosis General considerations Epidemiology Etiology and pathogenesis Clinical features Intrathoracic sarcoidosis Extrapulmonary lesions Investigations Radiological evaluation Chest X-ray High-resolution computed tomography (CT) Gallium scan Magnetic resonance imaging (MRI) and positive emission tomography scan (PET) Histology Immunology Noninvasive tests Course and prognosis Ocular manifestations Posterior segment disease Diagnosis Course and prognosis Therapy Established therapy Biologics Conclusion References 79 Intermediate Uveitis Introduction Epidemiology and demographics Presentation and clinical findings Imaging Differential diagnosis and workup Histopathology and pathophysiology Pars planitis Sarcoidosis Treatment Unilateral disease Bilateral disease Diagnostic and therapeutic vitrectomy Clinical course and complications Clinical course Complications References 80 Rheumatic Disease Introduction An approach to the assessment of the patient with possible rheumatic disease Common ocular presentations of rheumatic disease Keratoconjunctivitis sicca and other corneal presentations Scleritis/episcleritis Scleritis Episcleritis Uveitis Acute anterior uveitis Chronic anterior uveitis Intermediate uveitis Posterior uveitis Panuveitis Other retinal presentations Orbital presentations Neuro-ophthalmic presentations Investigations Therapeutic considerations Disease-specific section Rheumatoid arthritis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Seronegative spondyloarthropathies General considerations Epidemiology Ankylosing spondylitis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Reactive arthritis (previously known as Reiter syndrome) General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Inflammatory bowel disease General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Psoriatic arthritis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Juvenile idiopathic arthritis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Systemic lupus erythematosus General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Sj?gren syndrome General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Sarcoidosis Familial juvenile systemic granulomatosis (Blau syndrome) General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Scleroderma General considerations Epidemiology Articular and systemic disease Ocular disease Treatment of systemic disease Treatment of ocular disease Polymyositis and dermatomyositis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Relapsing polychondritis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Treatment of systemic disease Treatment of ocular disease Primary systemic vasculitis Progression and prognosis of primary systemic necrotizing vasculitis Aims of therapy Induction stage Maintenance stage Adjuvant therapy Treatment of relapse Alternative approaches to therapy Large vessel vasculitides Giant cell arteritis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Takayasu’s arteritis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Medium vessel vasculitides Polyarteritis nodosa General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Kawasaki disease General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Small vessel vasculitides Granulomatosis with polyangiitis (Wegener’s granulomatosis) General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Microscopic polyangiitis General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Churg–Strauss syndrome General considerations Epidemiology Articular and systemic disease Ocular disease Treatment Ocular complications of rheumatological therapies General Corticosteroids Antimalarials References 81 HIV-Associated Infections Epidemiology of hiv infection and aids Occupational exposure to HIV HIV virology and pathogenesis Therapy of HIV infections Clincial spectrum of HIV Infection control related to HIV Ocular findings in aids: an overview Noninfectious retinopathy Infectious retinopathy Cytomegalovirus retinitis Pathogenesis, diagnosis, and clinical manifestations Screening techniques for retinal and systemic CMV infection Treatment of CMV retinitis Systemic therapy of CMV retinitis Intravenous ganciclovir Oral ganciclovir Valganciclovir Foscarnet Cidofovir CMV resistance Treatment strategies in resistant CMV Combination therapies: ganciclovir–foscarnet Summary of initial systemic CMV retinitis treatment Intraocular therapy of viral retinitis Ganciclovir Foscarnet Ganciclovir intraocular device Intravitreal cidofovir Fomivirsen Investigational agents for CMV retinitis Maribavir Tomeglovir Rhegmatogenous retinal detachment in CMV retinitis HIV disease/CMV retinitis in the HAART era Immune recovery uveitis Other complications of CMV retinitis Herpetic retinitis Acute retinal necrosis in HIV patients Progressive outer retinal necrosis Nonviral intraocular infections in AIDS patients Pneumocystis carinii choroidopathy Ocular toxoplasmosis Fungal diseases Candida albicans Cryptococcus neoformans Histoplasmosis Aspergillosis Coccidioidomycosis Paracoccidioidomycosis Advances in antifungal therapy Bacterial retinitis Syphilis Invasive diagnostic techniques for retinal disease Antiretroviral therapy Synopsis References 82 Mycobacterial Infections Introduction Pulmonary and extrapulmonary tuberculosis Ocular tuberculosis Differential diagnosis Pathogenesis Nontuberculous mycobacterial infections Latent tuberculosis Laboratory evaluation Treatment Drug-resistant tuberculosis References 83 Eales Disease Introduction Clinical features and natural history Pathology and pathogenesis Differential diagnosis Primary retinal vasculitis Diagnostic workup for eales disease Management Summary References 84 Spirochetal Infections Introduction Syphilitic uveitis Epidemiology and pathogenesis Ocular manifestations Diagnosis Differential diagnoses Treatment Course and outcome Uveitis associated with lyme disease Epidemiology and pathogenesis Ocular manifestations Diagnosis Differential diagnoses Treatment Disease course and outcome Ocular leptospirosis Epidemiology and pathogenesis Ocular manifestations Diagnosis Treatment Disease course and outcome References 85 Ocular Toxoplasmosis Introduction Biology, life cycle, and transmission Strains/clonal populations: haplogroups genetics Pathogenesis Ocular disease Laboratory techniques Outcomes and complications Treatment and prevention References 86 Helminthic Disease Introduction Ocular toxocariasis History Parasitology Pathophysiology Clinical presentations Peripheral granuloma Posterior pole granuloma Chronic endophthalmitis Atypical presentations Diagnosis Differential diagnosis Retinoblastoma Toxoplasmosis Other forms of endophthalmitis and uveitis Retinopathy of prematurity Coats disease Persistent hyperplastic primary vitreous Familial exudative vitreoretinopathy Treatment Diffuse unilateral subacute neuroretinitis History and etiology Epidemiology Pathophysiology Clinical presentation Early stage Late stage Diagnosis Differential diagnosis Treatment Onchocerciasis Clinical presentation Treatment and prevention Cysticercosis Clinical presentation Treatment References 87 Endogenous Endophthalmitis: Bacterial and Fungal Epidemiology and risk factors Clinical assessment of the patient Medical evaluation of the patient Endogenous bacterial endophthalmitis Endogenous fungal endophthalmitis Treatment strategies Systemic pharmacotherapies Intravitreal pharmacotherapies Surgical treatments Suggested management References 88 Acute Retinal Necrosis Syndrome Definition Patient population Etiology Pathologic features Differential diagnosis Treatment and prognosis References Section 5: Miscellaneous 89 Drug Toxicity of the Posterior Segment Disruption of the retina and retinal pigment epithelium Phenothiazines Thioridazine Chlorpromazine Chloroquine derivatives Chloroquine Hydroxychloroquine Quinine sulfate Clofazimine Dideoxyinosine (DDI) Deferoxamine Corticosteroid preparations Cisplatin and BCNU (carmustine) Miscellaneous agents Vascular damage Quinine sulfate Cisplatin and BCNU (carmustine) Talc Oral contraceptives Aminoglycoside antibiotics Interferon Miscellaneous agents Cystoid macular edema Epinephrine Nicotinic acid Latanoprost Paclitaxel/docetaxel Retinal folds Sulfa antibiotics, acetazolamide, chlorthalidone, disothiazide, ethoxyzolamide, hydrochlorothiazide, metronidazole, sulphonamide, topiramate, triamterene Crystalline retinopathy Tamoxifen Canthaxanthine Methoxyflurane Talc Miscellaneous agents Uveitis Rifabutin Cidofovir Latanoprost Miscellaneous Cardiac glycosides Methanol Vigabatrin Sildenafil, tadalafil, vardenafil Summary References 90 Photic Retinal Injuries: Mechanisms, Hazards, and Prevention Photomechanical effects Photomechanical mechanisms Photomechanical retinal injuries Photothermal effects Photothermal mechanisms Photothermal retinal injuries Operating room or medical office injuries Slit-lamp photocoagulators Laser pointers and other consumer laser devices Photochemical effects Photochemical mechanisms Photochemical retinal injuries Solar and welder’s maculopathy Operating microscope and endoilluminator injuries Ophthalmoscope and fundus camera exposure Environmental issues Light and macular degeneration Sunglasses Safety standards Practical considerations Conclusion References 91 Traumatic Chorioretinopathies Epidemiology Chorioretinopathies from direct ocular injuries Commotio retinae Retinal concussion Retinal contusion Choroidal rupture Traumatic macular hole Traumatic chorioretinal rupture Traumatic retinal pigment epithelial tears Traumatic retinal tears and detachments Retinal dialyses Optic nerve avulsion Chorioretinopathies from indirect ocular injuries Purtscher’s retinopathy Terson’s syndrome Shaken-baby syndrome Valsalva retinopathy Fat embolism syndrome Whiplash retinopathy Acknowledgments References 92 Pregnancy-Related Diseases Retinal and choroidal disorders arising in pregnancy Pre-eclampsia and eclampsia Retinopathy in pre-eclampsia and eclampsia Choroidopathy in pre-eclampsia and eclampsia Other ocular changes seen in pre-eclampsia and eclampsia Central serous chorioretinopathy Occlusive vascular disorders Retinal artery occlusion Retinal vein occlusion Disseminated intravascular coagulopathy Thrombotic thrombocytopenic purpura Amniotic fluid embolism Uveal melanoma Other changes arising in pregnancy Pre-existing conditions Diabetic retinopathy Progression of diabetic retinopathy during pregnancy Short- and long-term effects of pregnancy on diabetic retinopathy The role of baseline retinopathy status, duration of diabetes, and metabolic control No initial retinopathy Mild nonproliferative diabetic retinopathy Moderate to severe nonproliferative diabetic retinopathy Proliferative retinopathy Diabetic macular edema in pregnancy Other risk factors for progression of diabetic retinopathy during pregnancy Diabetic retinopathy and maternal and fetal wellbeing Toxoplasmic retinochoroiditis Noninfectious uveitis Other retinal disorders Diagnostic testing and therapy Photodynamic therapy Anti-VEGF therapy Conclusion References 93 Optic Disc Anomalies, Pits, and Associated Serous Macular Detachment Optic disc anomalies Megalopapilla Aplasia Hypoplasia Cavities in the optic nerve head Anatomy Optic disc pits Visual defects Associated retinal changes Macular detachment Appearance of maculopathy Course of associated serous macular detachment Theories of pathophysiology Prognosis Treatment References 94 Retina-Related Clinical Trials: A Resource Bibliography Diabetic retinopathy Diabetic Retinopathy Study (DRS) UK Multicentre Controlled Study Diabetic Retinopathy Vitrectomy Study (DRVS) Early Treatment Diabetic Retinopathy Study (ETDRS) Sorbinil Retinopathy Trial (SRT) Krypton Argon Regression of Neovascularization Study (KARNS) Diabetes Control and Complications Trial (DCCT) UK Prospective Diabetes Study (UKPDS) Diabetic Retinopathy Clinical Research Network (DRCR.net) Other diabetic retinopathy trials Vein occlusions Cochrane Systematic Review Branch Vein Occlusion Study (BVOS) Central Vein Occlusion Study (CVOS) Standard Care vs COrticosteroid for REtinal Vein Occlusion Study (SCORE) Other clinical trials for vein occlusion Age-related macular degeneration and other conditions associated with choroidal neovascularization Treatment trials Macular Photocoagulation Study (MPS) Other trials of laser treatment of choroidal neovascularization and a Cochrane systematic review Trials of photodynamic therapy with verteporfin (Visudyne) and a Cochrane systematic review Submacular Surgery Trials (SST) Trials of radiotherapy for choroidal neovascularization and a Cochrane systematic review Trials of anti-VEGF therapy for choroidal neovascularization V.I.S.I.O.N. MARINA ANCHOR FOCUS ABC Trial PIER and other randomized trials of ranibizumab for neovascular age-related macular degeneration Comparison of Age-related Macular Degeneration Treatments Trial (CATT) Trials of other pharmacologic treatments for choroidal neovascularization Prevention trials Age-Related Eye Disease Study (AREDS and AREDS 2) Complications of AMD Prevention Trial (CAPT) Other trials of potential preventive treatment for age-related macular degeneration and a Cochrane systematic review Retinopathy of prematurity Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Multicenter Study of Light Reduction in Retinopathy of Prematurity (LIGHT-ROP) Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) Early Treatment of Retinopathy for Prematurity (ETROP or EARLY-ROP) Other retinal and retina-related conditions Collaborative Ocular Melanoma Study (COMS) Studies of the Ocular Complications of AIDS (SOCA) Trials of treatment of posterior uveitis Silicone Study Macular hole trials Retinitis pigmentosa VOLUME 3 Part 1: Surgical Retina Section 1: The Pathophysiology of Retinal Detachment and Associated Problems 95 Pathogenetic Mechanisms of Retinal Detachment Major types Rhegmatogenous retinal detachment Traction retinal detachment Combined tractional and rhegmatogenous retinal detachment Exudative and hemorrhagic retinal detachment Conclusion References 96 Nonrhegmatogenous Retinal Detachment Introduction Pathophysiology Idiopathic Central serous chorioretinopathy Bullous retinal detachment Chronic CSCR Uveal effusion syndrome Vascular Coats disease Accelerated hypertension and pregnancy-induced hypertension Pregnancy-induced hypertension Diabetic retinopathy Vascular occlusive diseases Collagen vascular diseases Inflammatory and infectious Vogt–Koyanagi–Harada syndrome Sympathetic ophthalmia (SO) Posterior scleritis Infections associated with exudative detachment Bacterial infection Fungal infection Viral infection Degenerative Age-related macular degeneration and polypoidal choroidal vasculopathy Tumor and malignancy Choroidal hemangioma Choroidal melanoma Metastatic tumors Lymphoma Leukemia Disc anomalies Optic nerve pit Morning glory syndrome Other conditions Postsurgical exudative retinal detachment Disseminated intravascular coagulopathy Post-organ transplantation or hemodialysis exudative detachment Miscellaneous Conclusion References 97 Pathogenesis of Proliferative Vitreoretinopathy Introduction Cellular basis of PVR Composition of membranes RPE cells Glial cells Blood-borne cells Stimulation of cellular proliferation and migration Blood components Platelet-derived growth factor (PDGF) Transforming growth factor-? Monocyte chemotactic protein-1 (MCP1) Basic fibroblast growth factor (bFGF) Hepatocyte growth factor (HGF) Connective tissue growth factor (CTGF) Epidermal growth factor (EGF) Vascular endothelial growth factor (VEGF) Cytokines Extracellular matrix remodeling Biomarkers Conclusion References 98 Pathophysiology of Ocular Trauma Introduction Anatomic change Histopathologic findings Experimental models Wound healing and traumatic proliferative vitreoretinopathy Cellular constituents Growth factors Extracellular matrix Special conditions Traumatic endophthalmitis Intraocular foreign body Combat ocular injury Therapeutic aspects Surgical approach Pharmacologic approach Conclusion References Section 2: Retinal Reattachment: General Surgical Principles and Techniques 99 The Effects and Action of Scleral Buckles in the Treatment of Retinal Detachment Effects of scleral buckles on the geometry of the eye Axial length changes after scleral buckles Refractive errors caused by scleral buckles Astigmatic errors Spherical equivalent errors Scleral chord versus scleral arc length Effects on the internal geometry of the eye Volume changes in the eye after scleral buckles Scleral buckles and ocular rigidity Scleral buckles and ocular blood flow Effects of scleral buckles on the RPE and retina An overview of forces acting on the retina Forces that lead to retinal tears and detachments Vitreous traction Fluid movement and retinal breaks Epiretinal membranes, cellular proliferation, and retinal breaks Forces that promote attachment of the retina Physiologic adhesion between retina and RPE Thermal chorioretinal adhesions Scleral buckles and vitreous traction Scleral buckles and traction on the retinal surface Scleral buckles and fluid movement Conclusion References 100 Techniques of Scleral Buckling Introduction Surgical anatomy Coats of the eye Extraocular muscles Choroidal vasculature Innervation Preoperative assessment Finding the retinal break Lincoff’s rules Scheduling surgery Preparation for surgery Anesthesia Positioning the head for surgery Preparation and draping Surgical steps Conjunctival peritomy Slinging rectus muscles Reoperations Examination under anesthesia and break localization Retinopexy Cryotherapy Diode laser Photocoagulation Choice of retinopexy technique Choice of scleral explant Scleral sutures Tying the sutures Subretinal fluid drainage Indications for drainage Technique of drainage Timing Location of drain sites Drainage techniques Cut down techniques Single-stage techniques Comparison of techniques After drainage Air injection Encirclement Final examination of the retina Closure Documentation Outcomes Postoperative complications Recurrent retinal detachment Glaucoma Epiretinal membranes Extrusion/infection Band migration Diplopia Anterior segment ischemia References 101 Principles and Techniques of Vitreoretinal Surgery Vitreoretinal surgical anatomy Mechanics of vitreoretinal surgery Peeling Shear Fatigue failure Infusion system management Vitreous cutter considerations Control systems Microscope requirements Tool ergonomics Surgical steps Transconjunctival, small gauge vitrectomy Sclerotomies Vitreous removal Lens management Epiretinal membrane management Management of subretinal proliferation Extrusion techniques Interfacial surface tension management Fluid–air exchange Air–gas exchange Liquid perfluorocarbon Air–silicone exchange Perfluorocarbon–silicone oil exchange Retinectomy Hemostasis Retinopexy Panretinal photocoagulation Subconjunctival pharmacotherapeutics Surgical algorithms Conclusion References 102 Primary Vitrectomy in Rhegmatogenous Retinal Detachment Introduction Pathogenesis of Rhegmatogenous Retinal Detachment Categories of Rhegmatogenous Retinal Detachment Patient selection for primary vitrectomy Principles of vitrectomy Surgical techniques Create three ports through the pars plana Core vitrectomy Peripheral vitrectomy Fluid–air exchange Photocoagulation/cryopexy of the retinal tear Tamponade Positioning after surgery Vitrectomy with encircling buckling Vitrectomy with phacoemulsification and intraocular lens implantation Sutureless microincision vitrectomy surgery Surgical outcomes Prognostic factors Complications Perspectives References 103 Pneumatic Retinopexy Introduction History Basic principles Intraocular gases Retina–gas interface Case selection Extent of breaks Inferior breaks Proliferative vitreoretinopathy Inability to maintain positioning Glaucoma Cloudy media Lattice degeneration Aphakia and pseudophakia Posterior vitreous detachment Cases where pneumatic retinopexy presents a particular advantage Surgical technique Anesthesia One-session versus two-session procedure Cryopexy versus laser Applying retinopexy Amount and type of gas to inject Sterilization of the ocular surface Preparation of the gas Performing a paracentesis Injection of gas Assessing intraocular pressure Instructing the patient Special procedures Fish eggs Gas entrapment at the injection site Steamroller Summary of procedure Postoperative management Results Comparison of pneumatic retinopexy with scleral buckle Comparison of pneumatic retinopexy with vitrectomy Complications Proliferative vitreoretinopathy New or missed retinal breaks Subretinal gas Acceptance of Pneumatic Retinopexy Algorithm for choosing Pneumatic Retinopexy versus other procedures for retinal detachment Conclusion References 104 Special Adjuncts to Treatment Special adjunct to treatment Introduction Physical properties of intraocular gases Functions of gas Internal tamponade Unfolding and folding of the retina Postoperative visualization Replace globe volume Dynamics of the gas bubble inside the eye Different phases of gas resorption Special considerations when under general anesthesia Response to changes in altitude Preparation for injection Clinical applications and surgical techniques In vitrectomy for retinal detachments In pneumatic retinopexy In scleral buckling for retinal detachments In macular hole surgery In displacement of subretinal blood In postvitrectomy gas exchange Postoperative care Head posture after intraocular gas injection Fundal exam in the postoperative period Intraocular pressure measurements Laser photocoagulation Vision change after surgery Changes in altitude Complications and management Cataract formation Raised intraocular pressure Hypotony Subretinal gas Gas in the anterior chamber and corneal decompensation Intraocular lens capture Conclusion Perfluorocarbon liquid in vitreoretinal surgery Introduction Types and properties of perfluorocarbon liquid Technique of perfluorocarbon liquid injection Technique of perfluorocarbon liquid removal Indications for use Proliferative vitreoretinopathy Vitreous base shaving Giant tears Ocular trauma Dislocated lens Suprachoroidal hemorrhage Other indications Complications and management Subretinal PFCL Intraocular toxicity PFCL in the anterior chamber Conclusion Silicone oil in vitreoretinal surgery Introduction Background Chemical properties of silicone oil Physical properties of silicone oil Specific gravity Buoyancy Surface tension and interfacial tension Viscosity Indications Retinal detachments with proliferative vitreoretinopathy Giant retinal tears Severe proliferative diabetic retinopathy Macular hole Viral retinitis Complicated pediatric retinal detachments Retinal detachments associated with choroidal coloboma Trauma Endophthalmitis Surgical techniques of silicone oil infusion General considerations Considerations of lens status Silicone oil infusion in small gauge vitrectomy systems Air–silicone oil exchange Perfluorocarbon liquid–silicone oil exchange Complications Silicone oil in the anterior chamber Glaucoma Chronic hypotony Cataract formation Recurrent retinal detachment Emulsification Keratopathy Unexplained visual loss following silicone oil tamponade Silicone oil removal Permanent silicone oil tamponade Conclusion The concept of heavy tamponade Background Newer generation of heavy tamponades Technique Complications Corneal toxicity Cataract formation Intraocular inflammation Emulsification Sticky silicone oil Adherent silicone oil on intraocular lens Hypotony Raised intraocular pressure Redetachment and proliferative vitreoretinopathy Conclusion Drugs for the prevention of proliferative vitreoretinopathy Introduction Pharmacological agents that have been tested in clinical trials Corticosteroids Fluoropyrimidines Daunorubicin Retinoids Heparin and low-molecular-weight heparin Chemicals that are yet to be tested in clinical trials Summary References 105 Optimal Procedures for Retinal Detachment Repair Introduction Round hole retinal detachment Introduction Natural history Conservative management Treatment Laser demarcation Scleral buckling Detachment due to retinal dialyses Introduction Natural history Conservative management Treatment Laser demarcation Scleral buckling Retinal detachment secondary to “u” (“horseshoe”) tears Introduction Natural history Conservative management Treatment Laser demarcation Pneumatic retinopexy Scleral buckling Vitrectomy Conventional indications Supplementary buckle Laser versus cryotherapy Sutureless vitrectomy Variations Conclusion References 106 Prevention of Retinal Detachment Introduction Risk factors for retinal detachment Symptomatic eyes Tears with persistent vitreoretinal traction Horseshoe-shaped tears Round tears Tears unassociated with persistent vitreoretinal traction Retinal holes and precursors of retinal detachment Asymptomatic eyes without high-risk factors Vitreoretinal precursors of retinal breaks Lattice degeneration Cystic retinal tufts Degenerative retinoschisis Asymptomatic retinal breaks Asymptomatic nonfellow eyes with high-risk factors Myopic nonfellow eyes Aphakic and pseudophakic nonfellow eyes Family history of retinal detachment Asymptomatic patients with retinal detachment in the fellow eye Asymptomatic phakic fellow eyes Precursors of retinal breaks Retinal breaks Giant retinal tears Asymptomatic aphakic and pseudophakic fellow eyes Precursors of retinal breaks Retinal breaks Giant retinal tears Prophylactic therapy in eyes undergoing vitreoretinal surgery During silicone oil removal in previously operated eyes During primary vitrectomy for nonretinal detachment During pneumatic retinopexy Summary regarding therapy during vitreoretinal surgery Treatment methods Cryotherapy Laser photocoagulation Surgical techniques Cryotherapy Laser photocoagulation Scleral buckling Results and complications of prophylactic therapy Results of prophylactic therapy Flap tears Lattice degeneration Retinal holes Patients with previous retinal detachment in the fellow eye Complications of prophylactic treatment Conclusion References Section 3: Complicated Forms of Retinal Detachment 107 Proliferative Vitreoretinopathy Introduction Pathophysiology Risk factors for development of PVR Clinical signs and diagnosis of PVR Classification of PVR Prevention of PVR Surgery for PVR Scleral buckling and PVR Vitrectomy and PVR Surgical steps for established PVR Anesthesia Operative technique Management of the lens in PVR Core vitrectomy and removal of the vitreous base Removal of epiretinal membranes and use of perfluorocarbon heavy fluid Removal of anterior tractional membranes Testing adequacy of relief of traction and relaxing retinotomy Removal of subretinal membranes Fluid–air exchange Creating chorioretinal adhesion and scleral indentation Intraocular tamponade Silicone oil Heavy silicone oil Removal of silicone oil Postoperative management Complications after PVR surgery Intraoperative complications Early postoperative complications Late postoperative complications Medical adjunctive therapy for PVR Results of surgery for PVR When IS surgery for PVR not justified? References 108 Retinotomies and Retinectomies Introduction Drainage retinotomy General principles Surgical technique in conjunction with perfluorocarbon liquid (PFCL) Surgical technique without PFCL Complications Retinotomy to gain access to the subretinal space Subretinal foreign body Removal of subretinal PFCL Retinal or subretinal mass Retinotomies to mobilize retina: macular translocation Retinotomies to obtain abnormal retinal tissue: retinal biopsy Retinectomy for treatment of intractable glaucoma Relaxing retinotomy and retinectomy General surgical principles and techniques Retinal incarceration in traumatic or surgical wounds Surgical technique Retinal shortening (contraction) because of PVR Surgical technique Focal OR diffuse retinal contraction Circumferential contraction Anterior retinal displacement Intrinsic retinal contraction Extensive periretinal fibrous proliferation Prophylactic removal of anterior flap of horseshoe tears Contraction and fibrosis of flap of giant retinal tear Inner-wall retinectomy for complications of congenital retinoschisis Retinal shortening because of proliferative vascular retinopathy Management of retinotomy and retinectomy Results Complications References 109 Giant Retinal Tear Introduction Etiology Iatrogenic giant retinal tear Pathogenesis History of management of giant retinal tear Preoperative evaluation and planning Ultrasonographic diagnosis of giant retinal tear Proliferative vitreoretinopathy Role of nonsurgical treatment Laser barrage photocoagulation Outpatient fluid–gas exchange followed by cryopexy or laser photocoagulation Role of simple scleral buckling Technique of simple scleral buckling Vitreous surgery Role of an encircling band along with vitreoretinal surgery Lens management Management of intraocular lens Visualization Vitrectomy Radical excision of the vitreous base Mobilizing the retina and management of anterior retinal flap Eyes with PVR Conversion to a 360° tear Perfluorocarbon liquids Injection of PFCL Retinopexy Internal tamponade PFCL–air exchange PFCL–silicone oil exchange Alternative techniques Additional steps Results Management of fellow eye References 110 Surgery for Ocular Trauma: Principles and Techniques of Treatment Extent of ocular injuries Ocular trauma classification Closed-globe injuries Hyphema Lens subluxation and dislocation Vitreous hemorrhage “Commotio retinae”, avulsion of the vitreous base, and retinal tears Retinal detachment and macular hole Open-globe injuries Preoperative evaluation Repair of laceration Management of intraocular foreign body Perforating injury Vitreous hemorrhage and retinal detachment Endophthalmitis Cataract Late complications of penetrating injury Sympathetic ophthalmia Prevention Conclusion References 111 Surgery for Proliferative Diabetic Retinopathy Introduction Indications and timing of surgery Cataract High-risk retinal neovascularization Fibrovascular proliferations Vitreous hemorrhage Macular traction and macular edema Retinal detachment Tractional retinal detachment Combined tractional–rhegmatogenous retinal detachment Neovascular glaucoma Preoperative evaluation and informed consent Surgery Education and training Anesthesia Preoperative preparation Surgical equipment Microscope and lenses Microinstruments and illumination Small-gauge systems Basic equipment Vitrectomy cutter Illumination Membrane dissecting instruments Retinopexy instrumentation Dyes and tamponades Additional equipment Surgical procedure Cataract surgery Glaucoma surgery Aqueous shunt procedures Cyclodestructive therapy Pars plana vitrectomy Preparation of entry sites Vitrectomy Eyes with complete posterior hyaloid separation Eyes with incomplete posterior hyaloid separation Eyes with subtotal posterior vitreous adhesion Eyes with combined tractional and rhegmatogenous detachment Photocoagulation Tamponades Wound closure Postoperative care Examinations Hospitalization and convalescence Medications Further surgery Diabetes control Complications Intraoperative complications Cornea, anterior chamber, lens Reduced visualization Corneal edema Pupillary constriction Lens touch, cataract formation Intraocular hemorrhage Retinal breaks and detachment Subretinal perfluorocarbon or silicone oil Postoperative complications Anterior segment Conjunctival complications Corneal complications Uveitis Iris neovascularization and neovascular glaucoma Cataract formation Intraocular pressure elevation Fibrinoid syndrome Vitreous hemorrhage Anterior hyaloidal fibrovascular proliferation Results of surgery by evidence-based trials Cataract Vitreous hemorrhage Diabetic maculopathy and macular traction Retinal detachment, tractional detachment and proliferative vitreoretinopathy Secondary glaucoma (neovascular glaucoma) Conclusion References 112 Management of Combined Inflammatory and Rhegmatogenous Retinal Detachment Introduction Epidemiology Pathophysiology Clinical examination and findings Management RD with active inflammation Persistent inflammatory SRD RD with retinal necrosis Cytomegalovirus retinitis Acute retinal necrosis Prognosis Conclusion References 113 High Myopia and the Vitreoretinal Complications Introduction Retinal detachment from peripheral breaks Epidemiology of surgical macular complications Rhegmatogenous retinal detachment after refractive surgeries Etiology and pathophysiology Myopic foveoschisis Macular hole with or without retinal detachment Posterior retinal detachments from paravascular microholes Symptoms of myopic foveoschisis and macular holes with or without retinal detachments Clinical findings Optical coherence tomography features Fundus autofluorescence Treatment of foveoschisis Surgical indications Surgical prognosis Surgical procedures Vitreous separation Internal limiting membrane peeling Tamponade Macular buckling Postoperative complications Conclusion References 114 Retinopathy of Prematurity Introduction Classification system Histophysiologic features, clinically relevant cell biology, and pathophysiology Stages 1 and 2 Stage 3 Distortion of retinal vascular architecture Stages 4 and 5 Development of stage 4A ROP retinal detachments Clinical considerations Photographic imaging Cryotherapy Indirect laser photocoagulation The Early Treatment Retinopathy Of Prematurity study (ETROP) Type 1 pre-threshold Type 2 pre-threshold Anti-vascular endothelial growth factor therapy Therapeutic oxygen Stages 4 and 5 preoperative evaluation Surgical therapy Scleral buckling Lens-sparing vitrectomy for 4A ROP Vitrectomy for 4B ROP Lensectomy, vitrectomy, and membrane peeling Enzymatic manipulation of the vitreoretinal junction Surgical approach Lens-sparing vitrectomy Ab interno incision Closed lensectomy pars plicata vitrectomy References 115 Surgery for Pediatric Vitreoretinal Disorders General aspects Development of the child’s eye and surgical consequences Examination of pediatric patients Preoperative treatment Surgical considerations and techniques Cornea and keratoprosthesis Lens management Posterior-segment surgical techniques Silicone oil and gas tamponade Indications for surgery Injuries Direct injury Open globe injury Closed globe injury Oradialysis Traumatic macular hole Vitreous hemorrhage Indirect injury Terson syndrome Shaken-baby syndrome Diseases of the pediatric retina Myopia Subfoveal membranes Coats disease Hereditary vitreoretinopathies Stickler syndrome Kniest dysplasia Familial exudative vitreoretinopathy Marfan syndrome Congenital X-linked retinoschisis Knobloch syndrome Incontinentia pigmenti Norrie disease Malformations Anomalies of the papilla Coloboma Persistent hyperplastic primary vitreous Retinopathy of prematurity (ROP) Conclusions References Section 4: Vitreous Surgery for Macular Disorders 116 Epiretinal Membranes Introduction Prevalence Classification Clinical features Pathogenesis Clinical assessment and differential diagnosis Investigations Optical coherence tomography Fluorescein angiography When to offer surgery and prognostic indicators Surgery Use of vital dyes to assist in ERM peeling Techniques for engaging and peeling ERMs Benefit of peeling internal limiting membrane in ERM surgery Intraoperative and postoperative complications Intraoperative Postoperative complications Cataract Retinal detachment Recurrence Conclusion References 117 Macular Hole Introduction History Epidemiology and risk factors for idiopathic full-thickness macular holes Prevalence Incidence in the fellow eye Risk factors Pathogenesis, from posterior vitreous detachment to impending macular hole History of theories on the pathogenesis of macular hole Vitreomacular traction Foveal cyst Contraction of the premacular vitreous cortex Update on the pathogenesis of macular hole based on SD-OCT Early stages of posterior vitreous detachment How does PVD start in normal individuals? Early changes in foveal tissue (Stage 0 macular hole) Impending macular hole Stage 1A Stage 1B Clinical and imaging features of full-thickness macular hole Stage 2 macular hole Stage 3 macular hole Stage 4 macular hole Macular hole and epiretinal membrane OCT classification of macular hole Differential diagnosis Lamellar macular hole Histology of lamellar MH Biomicroscopy Optical coherence tomography Macular pseudoholes Optical coherence tomography Other round foveolar images Foveal cysts of various origins Microholes Non-idiopathic (secondary) MH Orbital trauma and high myopia High myopia Other rare causes Surgery for macular hole Introduction How do vitrectomy and gas work to close the hole? Releasing vitreous traction on the hole edge The healing process, histology, animal models, and early OCT Principles and techniques of macular hole surgery Posterior hyaloid detachment Extensive vitrectomy Epiretinal membrane peeling Internal limiting membrane peeling Vital dyes Indocyanine green and infracyanine Trypan blue Brilliant Blue Type of gas to use in MH surgery Use of silicone oil in MH surgery Use of healing adjuvants Peroperative complications Postoperative positioning Results of surgery Anatomic results Results according to hole size Results according to ILM peeling Results according to postoperative positioning Visual outcome Overall results Anatomic and visual correlation Postoperative complications of surgery Retinal detachment Cataract Visual field defects Reopening of macular holes Vitreolysis as A nonsurgical treatment for macular holes References 118 Cystoid Macular Edema and Vitreomacular Traction Introduction Historical discovery of macular edema Anatomy and pathophysiology of macular edema Anatomy of cystoid macular edema Pathophysiology of tractional macular edema Clinical signs of cystoid macular edema Imaging of cystoid macular edema Angiography Optical coherence tomography OCT and diabetic macular edema OCT in vitreomacular traction syndrome OCT for vitreomacular traction in age-related macular degeneration Surgical treatment of tractional macular edema Rationale for vitrectomy Tractional origin of macular edema Nontractional origin of macular edema Rationale for internal limiting membrane peeling Clinical entities with cystoid macular edema associated with vitreomacular traction Diabetic macular edema (DME) Role of vitrectomy in DME Role of internal limiting membrane peel in DME Surgical technique Pars plana vitrectomy Role of triamcinolone Internal limiting membrane peel Cystotomy for diabetic CME Central retinal vein occlusion Role of vitrectomy in CRVO Role of internal limiting membrane peel in CRVO Radial optic neurotomy (RON) Branch retinal vein occlusion (BRVO) Role of vitrectomy in BRVO Adventitial sheathotomy in BRVO Uveitic macular edema Role of vitrectomy in uveitic macular edema Role of internal limiting membrane peel in uveitic CME Postoperative macular edema Vitreomacular traction syndrome and epiretinal membrane Vitrectomy for vitreomacular traction in age-related macular degeneration Retinitis pigmentosa Pharmacologic vitreolysis References 119 Surgical Management of Choroidal Neovascularization and Subretinal Hemorrhage Choroidal neovascular membranes Introduction Surgical technique Early results Submacular surgery trials Current indications for surgical removal of CNV Submacular hemorrhage Introduction Etiology Natural history Management options Surgical removal of blood and CNV Vitrectomy, injection of subretinal tissue plasminogen activator, and aspiration of liquefied blood Intravitreal tissue plasminogen activator with pneumatic displacement Subretinal injection of tissue plasminogen activator with pneumatic displacement Anti-VEGF agents Conclusion References 120 Macular Translocation Background and rationale Animal studies Historical perspective and evolution of technique Principles of foveal relocation Preoperative considerations Indications History and retinal examination Diagnostic testing Surgical technique for macular translocation MTS360 Limited macular translocation Early postoperative management Positioning Laser treatment Extraocular muscle surgery following macular translocation Functional outcomes for macular translocation surgery Neovascular AMD Non-neovascular AMD Non-AMD diagnoses Postoperative surgical complications following macular translocation Retinal and RPE changes after macular translocation Unintentional macular translocation following retinal detachment repair Advantages of macular translocation and future directions References 121 Retinal Pigment Epithelium and Choroid Translocation in Patients with Age-Related Macular Degeneration Epidemiology Alternative treatments for AMD Exudative AMD Dry AMD Surgical treatment Rationale for reconstitution of retinal pigment epithelium Transplantation of a full-thickness patch from the midperiphery Surgery Keyhole approach Peroperative course Finding a cleavage plane between sclera and choroid Positioning the graft on the spatula Positioning of the graft under the fovea Tamponade Flapover approach Instruments Results in exudative AMD RPE transplantation in dry AMD Surgical aspects in dry AMD Conclusions for patient benefit in geographic atrophy RPE–choroid translocation and future stem cell treatments for AMD References Section 5: Vitreous Surgery: Additional Considerations 122 Infectious Endophthalmitis Introduction Organisms that cause endophthalmitis Bacteria Gram-positive cocci Staphylococci Streptococci Gram-positive bacilli Bacillus Corynebacterium diphtheriae Listeria monocytogenes Clostridium species Propionibacterium Gram-negative cocci Neisseria Moraxella Gram-negative bacilli Actinobacter Haemophilus influenzae Pseudomonas Enterobacteriaceae Klebsiella Higher bacteria Actinomyces Nocardia Fungi Candida Aspergillus spp. Histoplasma capsulatum Blastomyces dermatitidis Helminths, protozoa, and ectoparasites Helminths Protozoa Ectoparasites Experimental endophthalmitis Clinical findings Postoperative infection Cataract extraction Corneal transplantation Glaucoma filtration surgery Pars plana vitrectomy Intraocular injection Scleral buckling procedure Strabismus surgery Other Post-traumatic endophthalmitis Endogenous endophthalmitis Therapy Antimicrobial therapy Choice of antimicrobial agent Route of administration Antimicrobial agents Cephalosporins Vancomycin Aminoglycosides Fluoroquinolones Antifungal agents Pars plana vitrectomy Acute postoperative endophthalmitis after cataract surgery Traumatic endophthalmitis Chronic postoperative endophthalmitis Bleb-associated endophthalmitis Endogenous endophthalmitis Preoperative evaluation Surgical techniques Postoperative management Control of inflammation Complications Results Future directions Conclusion References 123 Diagnostic and Therapeutic Vitrectomy for Uveitis Introduction Diagnostic vitrectomy Indications Surgical principles and techniques Preoperative preparation Vitreous sampling Handling and preparation of vitreous samples Retinal or choroidal biopsy Diagnostic techniques for vitrectomy specimens Cytological evaluation Histopathologic evaluation Microbiological culture Molecular analysis Flow cytometry Cytokine/chemokine measurement Future directions Therapeutic vitrectomy Indications Surgical principles and techniques Outcomes Future directions Conclusion References 124 Vitreous, Retinal, and Choroidal Biopsy Introduction Vitreous biopsy Surgical technique Histologic technique and preparations Results Transvitreal retinal biopsy Surgical technique Histologic technique and preparation Results Transvitreal and transscleral choroidal biopsy Surgical technique Transvitreal biopsy Transscleral biopsy Histologic technique and preparations Results Fine-needle biopsy Surgical technique Results Complications of intraocular biopsy Conclusion References 125 Transplantation Frontiers Introduction Background and rationale for RPE transplantation in age-related macular degeneration Results of RPE transplants in humans Immune response to RPE transplants Immune privileged sites and immune privileged tissue Are RPE transplants rejected? RPE graft failure RPE replacement: future directions Immune rejection Transplanted RPE survival and differentiation on aged Bruch’s membrane Native RPE resurfacing of aged Bruch’s membrane Alternate source of rpe: stem cells Background and rationale for photoreceptor transplantation in retinal dystrophies Results of photoreceptor transplants in experimental animals Animal models of retinal degeneration Graft implantation sites and preparations Transplantation aimed at photoreceptor cell rescue Transplantation aimed at photoreceptor cell replacement Stem cells in photoreceptor transplantation Results of photoreceptor transplants in humans Immune response to photoreceptor transplants Photoreceptor transplantation: future directions Conclusions References 126 Artificial Vision Introduction Background and history of artificial vision Visual prostheses Cortical prosthesis Optic nerve prosthesis Retinal prostheses Pathology of retinitis pigmentosa and selected macular disorders Epiretinal prostheses ARGUS I ARGUS II Subretinal prosthesis Recent alternative approaches Electrotherapeutics Electrotherapeutics Optogenetics Conclusions from clinical trials Disclosures References 127 Pharmacology at Surgery Introduction Pharmacologic vitreolysis Rationale for pharmacologic vitreolysis Enzymatic vitreolysis – microplasmin, plasmin, and others Microplasmin Plasmin Hyaluronidase Dispase Antiproliferative agents in the management of proliferative vitreoretinopathy Tissue plasminogen activator in vitreoretinal surgery Visualization of the vitreoretinal interface Current dyes for epimacular membranes and the internal limiting membrane Perspectives VEGF inhibitors in vitreoretinal surgery Proliferative diabetic retinopathy and macular edema Retinopathy of prematurity Neovascular glaucoma Endophthalmitis Conclusion References Part 2: Tumors of the Retina, Choroid, and Vitreous Section 1: Tumors of the Retina 128 Retinoblastoma Introduction Clinical advances Basic science advances Genetics of retinoblastoma Clinical genetics Genetic terminology Molecular genetics of retinoblastoma The RB1 gene Low penetrance retinoblastoma RB1 gene mutations in other tumors The role of the retinoblastoma protein in tumor suppression The retinoblastoma protein The RB1 tumor suppressor pathway The RB-E2F regulatory network Molecular pathogenesis of retinoblastoma Retinoblastoma: the disease Terminology Overview of retinoblastoma Epidemiology Natural history of intraocular retinoblastoma Classification of intraocular retinoblastoma Reese–Ellsworth classification International Classification for Intraocular Retinoblastoma Disease prognosis Retinoblastoma survival rates Factors affecting survival Factors affecting salvage of eye and vision Diagnosis of retinoblastoma Signs and symptoms Diseases simulating retinoblastoma (pseudoretinoblastoma) Meeting the family and making a diagnosis Diagnostic workup Metastatic workup Staging examination under anesthesia The approach to the child with cancer Treat the child, not only the eye Treatment methods and techniques Developing a customized treatment plan Unilateral nonheritable retinoblastoma Bilateral retinoblastoma: symmetrical disease Advanced intraocular disease (groups D and E) Systemic intravenous chemotherapy Terminology Pre-1989 chemotherapy for extraocular disease Background of the currently used chemotherapy regimen Primary systemic chemotherapy Subtenon carboplatin Complications of primary systemic chemotherapy Heat and chemotherapy Intra-arterial (IA) chemotherapy Focal consolidation Laser Cryotherapy Radiation therapy External beam radiotherapy (teletherapy) Intensity modulated radiation therapy Proton beam radiotherapy Brachytherapy Enucleation Preoperative preparation for enucleation Surgical technique Tumor harvesting Surgical closure Postoperative care following enucleation Retrolaminar optic nerve involvement Post-treatment assessment and follow-up Regression patterns following treatment New tumors or tumor recurrences during post-treatment follow-up Late effects of treatment Bony hypoplasia of the midface (orbit) Radiation cataract Radiation retinopathy Neurocognitive deficits Second malignant neoplasms Visual acuity outcome Metastatic retinoblastoma Risk factors Survival Metastatic workup Extraocular (orbital) retinoblastoma Multicenter trials: Children’s Oncology Group Atypical retinoblastoma Retinoma (retinocytoma) Diffuse infiltrating retinoblastoma Retinoblastoma in older children Iatrogenic extraocular extension of tumor Trilateral retinoblastoma (primitive neural ectodermal tumors, pinealoma) References 129 Cavernous Hemangioma Introduction Clinical findings Differential diagnosis Ancillary studies Natural history Treatment Pathology Systemic and familial involvement Genetics Salient features References 130 Capillary Hemangioblastoma of the Retina and von Hippel–Lindau Disease Introduction Von hippel–lindau disease History Genetic associations Clinical presentation Clinical diagnosis Epidemiology of ocular lesions of von hippel–lindau disease Causes of vision loss Pathology of ocular lesions Treatment Anti-angiogenic treatments Screening and genetic testing for von hippel–lindau disease Conclusion References 131 Tuberous Sclerosis and the Eye Introduction History, diagnosis, and genetic basis Systemic manifestations Neurological Seizures Cognitive and behavioral disability Skin features Visceral features Skeletal features Ocular manifestations Retinal manifestations Optic nerve phakomas Ocular adnexal lesions Differential diagnosis Genetics References 132 Phakomatoses Introduction Definition of hamartia, hamartoma, chorista, choristoma Neurofibromatosis (von recklinghausen syndrome) Neurofibromatosis type 1 General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Neurofibromatosis type 2 General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Encephalofacial hemangiomatosis (sturge–weber syndrome) General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Racemose hemangiomatosis (wyburn-mason syndrome) General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Retinal cavernous hemangiomatosis General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Organoid nevus syndrome General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Phacomatosis pigmentovascularis General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Oculodermal melanocytosis General considerations Ophthalmologic features Dermatologic features Central nervous system features Other features Management Other phakomatoses Combined systemic hamartomatoses Conclusion References 133 Retinal Metastases Introduction Metastatic cascade Dissociation, invasion, and intravasation Hematogenous dissemination Extravasation and angiogenesis Review of case reports Demographics Clinical findings Symptoms Signs Differential diagnosis Diagnostic evaluation Treatment Prognosis Conclusion References 134 Remote Effects of Cancer on the Retina Introduction Cancer-associated retinopathy syndrome Cutaneous melanoma-associated retinopathy (MAR) syndrome Management of paraneoplastic retinopathy Bilateral diffuse uveal melanocytic proliferation Conclusion References 135 Melanocytoma of the Optic Disc General considerations Clinical features Pathology and pathogenesis Diagnostic approaches Management Conclusion References 136 Congenital Hypertrophy of the Retinal Pigment Epithelium Introduction Epidemiology/demographics Clinical findings and classification Solitary CHRPE Grouped CHRPE Multiple CHRPE Differential diagnosis Associated extraocular findings Pathophysiology/histopathology Clinical examination/ancillary testing Familial adenomatous polyposis prognosis and management options References 137 Combined Hamartoma of the Retinal Pigment Epithelium and Retina Historical review Epidemiology Clinical manifestations Symptoms Visual acuity Ophthalmoscopic appearance Associated ocular findings Systemic associations Diagnostic evaluation Differential diagnosis Epiretinal membrane Pigmented choroidal lesions Miscellaneous lesions Clinical course Etiology and pathogenesis Histopathology Treatment Medical Surgical References Section 2: Tumors of the Choroid 138 Choroidal Nevi Introduction Definitions Nevus Halo nevus Giant choroidal nevus Melanocytoma Ocular melanocytosis Prevalence Nevus Halo nevus Giant choroidal nevus Melanocytoma Ocular melanocytosis Choroidal nevi and systemic disease Uveal nevi and neurofibromatosis Dysplastic nevus syndrome Paraneoplastic bilateral diffuse uveal melanocytic proliferations Halo nevi Histopathology Cytology Plump polyhedral nevus cells Slender spindle nevus cells Intermediate nevus cells Balloon cells Secondary histologic changes in the neighboring tissues Choriocapillaris Drusen Retina and retinal pigment epithelium Controversial aspects Do all choroidal melanomas arise from nevi? Reappraisal of the Callender classification Updated classification Clinical findings Functional repercussions Clinical presentation Secondary changes in the overlying tissues Retinal pigment epithelial and Bruch’s membrane changes Serous detachment Choroidal neovascular membrane Clinical differential diagnosis Freckles Subretinal hemorrhages Congenital hypertrophy of the retinal pigment epithelium Small melanomas Ancillary studies Natural history Management of nevi Nonsuspicious nevi Suspicious nevi Serous detachment and choroidal neovascular membrane Acknowledgment References 139 Epidemiology of Posterior Uveal Melanoma Introduction Incidence Host factors Age and sex Race and ancestral origin Cancer genetics Ocular and cutaneous nevi and melanocytosis Hormones and reproductive factors Eye and skin color History of nonocular malignancy Environmental factors Sunlight exposure Diet and smoking Geography Occupational and chemical exposures Mobile phone use Other environmental exposures Conclusion References 140 Prognosis of Posterior Uveal Melanoma Ocular prognosis of globe-conserving therapies Radiation Nonradiation therapy Surgery Systemic prognosis for metastasis and death Radiation therapy Metastasis and survival Prognosis after enucleation Visual prognosis and ocular morbidity Clinical prognostic indicators for metastasis Tumor size Histopathologic prognostic indicators for metastasis Histopathology and immunogenetics Tumor microvasculature Extrascleral extension Molecular prognostic indicators for metastasis Conclusion References 141 Molecular Genetics of Choroidal Melanoma Introduction Cutaneous melanoma, uveal melanoma, and the ras/raf/mek pathway GNAQ and GNA11 mutations in uveal melanoma Chromosomal abnormalities in uveal melanoma Gain of 6p, loss of 3: the genetic bifurcation in uveal melanoma Gene expression profiling Clinical implications of genetic prognostication Tissue procurement Which test(s) should we use? Genetic testing in clinical trials Diagnosis and treatment of current uveal melanoma patients Conclusion References 142 Pathology of Choroidal Melanoma Introduction Processing of specimens Fixation Gross examination Staining Gross appearance of choroidal melanoma Histopathologic features of tumor cells and their prognostic relevance Cytologic features Immunohistochemical features Electron microscopy Other histopathologic characteristics and their prognostic relevance Tumor stroma Tumor extension Degenerative changes Special types of uveal melanoma Diffuse uveal melanoma Multifocal unilateral uveal melanoma Bilateral uveal melanoma Clear cell differentiation of uveal melanoma Balloon cell melanoma Necrotic melanoma Retinoinvasive melanoma Histologic changes after treatment Brachytherapy Proton beam irradiation Radiation retinopathy Transpupillary thermotherapy (TTT) APPENDIX: Histologic differential diagnoses Acknowledgments References References 143 Overview of Management of Posterior Uveal Melanoma Introduction General considerations Periodic observation Photocoagulation Transpupillary thermotherapy Radiotherapy Local resection Enucleation Orbital exenteration Management of systemic metastasis Counseling the patient Conclusion References 144 Enucleation for Choroidal Melanomas Introduction Purpose of enucleation Indications Implant description Implant sizing Enucleation technique Special considerations Optic nerve invasion and limited extrascleral extension Complications Conclusion References 145 Brachytherapy for Choroidal Melanoma Dosimetry Isotope selection Plaque design Indications for treatment Medium tumors Small tumors Large tumors Juxtapapillary tumors Plaque placement technique Postoperative observations Local tumor response Recurrences Visual results Adjuvant therapy Conclusion References 146 Charged-Particle Irradiation of Uveal Melanoma Introduction Treatment Patient selection Operative technique Treatment planning Treatment techniques Radiation dose Follow-up Clinical findings in treated patients Results Tumor regression Visual outcomes Complications Recurrence Enucleation Metastasis and survival Conclusion References 147 Surgical Resection of Choroidal Melanoma Introduction Exoresection Indications and contraindications Preoperative work-up Surgical technique Preparation Exposure Lamellar scleral dissection Ocular decompression Deep scleral incision Tumor excision Scleral closure Adjunctive brachytherapy Eye closure Variations in technique Ciliary body involvement Retinal adhesion Extraocular extension Exoresection without profound hypotensive anesthesia Postoperative management Anesthesia Outcomes Visual acuity Local tumor control Retinal detachment Other complications Metastatic death Endoresection Indications and contraindications Surgical technique Outcomes Secondary local resection for “toxic tumor” after radiotherapy Conclusions References 148 Laser Treatment of Choroidal Melanoma Introduction Laser techniques available for the treatment of intraocular tumors Photocoagulation Transpupillary thermotherapy Technique TTT as primary treatment of choroidal melanoma TTT as ancillary treatment of choroidal melanoma Laser photocoagulation as ancillary treatment for uveal melanoma Radiation retinopathy, radiation-induced optic neuropathy Surgical removal of uveal melanoma Exudative retinal detachment Photodynamic therapy of uveal melanomas Experimental techniques References 149 Systemic Evaluation and Management of Patients with Uveal Melanoma Introduction Physical examination Serology: liver function tests Radiologic assessment: computerized tomography, magnetic resonance imaging and ultrasonography Positron emission tomography/ computed tomography Pathology, genetics, and molecular biology Ethical considerations of screening and biopsy Treatment of metastatic disease Liver metastases Systemic metastases References 150 Collaborative Ocular Melanoma Study Introduction Background Design of the collaborative ocular melanoma study (coms) Randomized trials of radiotherapy Observational study Methods Chronology of the COMS Findings from the COMS trial of I-125 brachytherapy for medium choroidal melanoma Participants Survival estimates Complications Quality of life Findings from the COMS trial of pre-enucleation radiation for large choroidal melanoma Participants Survival estimates Complications Findings from the coms nonrandomized prospective study of small choroidal melanoma Histopathologic findings from enucleated eyes Other published findings Conclusion References 151 Choroidal Metastases Introduction Symptoms and clinical findings Frequency of primary cancer site Diagnostic evaluation Differential diagnosis Ophthalmic evaluation and ancillary tests Fluorescein angiography A- and B-scan ultrasonography Optical coherence tomography Fine-needle aspiration biopsy Systemic evaluation Unknown primary site Management Conventional external beam radiation therapy Brachytherapy plaques Stereotactic radiosurgery Protons Toxicity Ocular toxicity Nonocular toxicity Prognosis Conclusion References 152 Choroidal Osteoma General considerations Definition and incidence Clinical features Differential diagnosis Pathology and pathogenesis Diagnostic approaches Fluorescein angiography Indocyanine green angiography Ultrasonography Optical coherence tomography and autofluorescence Roentgenography Computed tomography Magnetic resonance imaging Radioactive phosphorus uptake Laboratory studies Management Prognosis Conclusion References 153 Circumscribed Choroidal Hemangioma Introduction Clinical features Differential diagnosis Ancillary studies Intravenous fluorescein angiography Indocyanine green angiography Ultrasonography Neuroimaging Optical coherence tomography and enhanced depth imaging Autofluorescence Pathology Treatment Photodynamic therapy Radiation External beam Plaque brachytherapy Proton beam Stereotactic radiosurgery Transpupillary thermotherapy Laser photocoagulation Anti-VEGF injection Conclusion References Section 3: Hematologic and Miscellaneous Tumors 154 Miscellaneous Uveal Tumors Introduction Epithelial tumors of the ciliary body: congenital Medulloepithelioma Glioneuroma Astrocytoma Epithelial tumors of the ciliary body: acquired Pseudoadenomatous hyperplasia: reactive Senile hyperplasia Adenomas and adenocarcinomas Melanocytic tumors Melanocytoma Bilateral diffuse uveal melanocytic proliferation associated with systemic malignant neoplasms Neurogenic tumors Neurilemmoma (schwannomas) Neurofibroma Granular cell tumor Myogenic tumors Leiomyoma Mesectodermal leiomyoma Miscellaneous Reactive lymphoid hyperplasia and lymphoma Juvenile xanthogranuloma Langerhans cell histiocytosis Hemangiopericytoma Rhabdomyosarcoma Choroidal biopsy Conclusion References 155 Leukemias and Lymphomas Introduction Systemic classification of leukemia and lymphoma Leukemia Prevalence and incidence Clinical manifestations Leukemic infiltrates Retinal or preretinal infiltrates Choroidal infiltrates Vitreous infiltrates Possible leukemic infiltrates Manifestations of anemia and thrombocytopenia Manifestations of hyperviscosity Opportunistic infections Prognosis Treatment Lymphomas Non-Hodgkin lymphoma Hodgkin lymphoma Treatment of lymphoma Mycosis fungoides Burkitt lymphoma Multiple myeloma and Waldenstr?m macroglobulinemia References 156 Primary Vitreoretinal Lymphoma Introduction Epidemiology Etiology and pathogenesis Clinical findings Ophthalmic findings Central nervous system findings Diagnosis Central nervous system involvement Differential diagnosis Treatment Ophthalmic treatment Central nervous system treatment Prognosis References Index A B C D E F G H I J K L M N O P Q R S T U V W X Z
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