RT Book, Section A1 Brodie, Scott E. A2 Murray, Michael F. A2 Babyatsky, Mark W. A2 Giovanni, Monica A. A2 Alkuraya, Fowzan S. A2 Stewart, Douglas R. SR Print(0) ID 1102706259 T1 Age-Related Macular Degeneration T2 Clinical Genomics: Practical Applications in Adult Patient Care YR 2014 FD 2014 PB McGraw-Hill Education PP New York, NY SN 9780071622448 LK accessmedicine.mhmedical.com/content.aspx?aid=1102706259 RD 2024/03/28 AB Disease summary:The “macula” is the central portion of the retina, where the greatest density of cone photoreceptors provides clear central vision. With increasing age, the macula is susceptible to disruption of the normal cellular architecture.In the early stages, toxic metabolic waste products, especially metabolites of the retinal photopigments, accumulate in the retinal pigment epithelial cells immediately beneath the retinal photoreceptors. Accumulations of photoreceptor debris overwhelm the cellular transport mechanisms and form extracellular deposits known as “drusen” between the retinal pigment epithelium and the underlying basement membrane. While small, isolated drusen are essentially innocuous, larger, coalescent drusen indicate a high risk of atrophic breakdown of the retinal pigment epithelium and the underlying capillary bed, the choriocapillaris. This often takes the form of sharply demarcated atrophic patches, referred to as “geographic atrophy” or “dry” macular degeneration. The overlying retinal photoreceptors cease to function, resulting in central scotomas and loss of visual acuity. In some cases, the underlying vascular bed reacts to the atrophic process by the elaboration of vascular membranes which proliferate under the retinal pigment epithelium, or between the retinal pigment epithelium and the retina. These neovascular membranes are prone to extravasation into the extracellular space, causing macular edema, as well as subretinal hemorrhage, again leading to loss of central vision. This “wet” or “exudative” macular degeneration is much less frequent than “dry” macular degeneration, but accounts for most cases of severe visual loss from macular disease.Age-related macular degeneration (AMD) (or macular degeneration, for short) is a leading cause of acquired blindness in developed countries, accounting for 54% of legal blindness in the United States.There is a strong racial predilection: prevalence among adults age 45 to 85 is 5.4% among Caucasians, 4.6% among ethnic Chinese, 4.3% among Hispanics, 2.4% among African Americans. The prevalence increases rapidly in all ethnic groups after age 80.Differential diagnosis:Geographic atrophy: hereditary macular dystrophies (Stargardt disease, retinitis pigmentosa, cone and cone-rod dystrophy, central areolar pigment epithelial dystrophy), congenital retinal abnormalities (coloboma, Leber congenital amaurosis), traumatic injuries, retinal drug toxicity.Exudative maculopathy: diabetic retinopathy with macular edema, central serous chorioretinopathy, juvenile retinoschisis, myopic retinal degeneration, Best vitelliform dystrophy, serpiginous choroiditis, familial exudative vitreoretinopathy, epiretinal membranes with macular pucker.Diagnosis is based on ophthalmoscopic appearance, then confirmed by fluorescein angiography to identify subretinal neovascularization, and optical coherence tomography imaging (OCT) to confirm and measure macular edema.Monogenic forms:No single-gene cause of age-related macular degeneration is known. Candidate genes which may contribute to risk for AMD include APOE (apolipoprotein E—found in drusen, affects lipid transport), and genes for several Mendelian disorders somewhat akin to AMD: ABCA4—Stargardt disease; TIMP3—Sorsby fundus dystrophy; VMD2—Best vitelliform dystrophy; Fibulin-3—Malattia leventinese, RDS-peripherin—pattern dystrophies; A4917G—a mitochondrial DNA polymorphism; TLR4—toll-like receptor 4.Family history:Comparison of prevalence of AMD between parents and children is difficult, as information about parents is frequently unavailable by the time their children are old enough to be at significant risk for AMD. After controlling for race and other known risk factors for AMD, the odds ratio (OR) for AMD in the siblings of patients with AMD compared with siblings of ...