age-related macular degeneration

**Pathophysiology** - Degeneration of the macula (central retina, fovea = highest cone density) due to dysfunction of the retinal pigment epithelium (RPE), Bruch membrane, and photoreceptors. - **Dry (non-exudative/atrophic) AMD (~85-90%)**: Drusen (yellow extracellular deposits of lipid/protein/complement components between RPE and Bruch membrane) accumulate. Progression leads to RPE and photoreceptor atrophy (geographic atrophy). Slow, gradual vision loss. - **Wet (exudative/neovascular) AMD (~10-15%)**: Choroidal neovascularization (CNV) driven by VEGF. Leaky, fragile vessels grow through Bruch membrane into the subretinal/sub-RPE space, causing fluid, hemorrhage, and fibrous scarring. Rapid, severe vision loss. Accounts for the majority of legal blindness from AMD.

**Risk factors** - Age (strongest), smoking (strongest modifiable), family history/genetics (complement factor H [CFH] Y402H polymorphism, ARMS2/HTRA1), White race, hypertension, cardiovascular disease, obesity, UV/light exposure, diet low in antioxidants/omega-3.

**Clinical features** - Painless, gradual (dry) or sudden/subacute (wet) central vision loss. - Metamorphopsia (straight lines appear wavy; assessed with the Amsler grid), central scotoma, difficulty reading and recognizing faces, trouble with dark adaptation. - Peripheral vision is preserved, so patients rarely become completely blind.

**Diagnosis** - Dilated fundoscopy: drusen (dry); subretinal hemorrhage, fluid, exudates, or a grayish-green lesion (wet). - Optical coherence tomography (OCT): first-line imaging to detect subretinal/intraretinal fluid and RPE changes. - Fluorescein angiography: shows leakage from CNV in wet AMD. OCT angiography is a noninvasive alternative. - Amsler grid for home monitoring.

**Management** - **Dry AMD**: No cure. AREDS2 supplementation (vitamin C, vitamin E, zinc, copper, lutein, zeaxanthin) slows progression in intermediate or advanced disease in one eye (it does not prevent disease onset). Beta-carotene was removed in AREDS2 because of increased lung cancer risk in smokers. Smoking cessation. Complement inhibitors (e.g., pegcetacoplan, avacincaptad pegol) are approved for geographic atrophy and slow lesion growth. - **Wet AMD**: Intravitreal anti-VEGF injections (ranibizumab, bevacizumab, aflibercept, faricimab) are first-line and can stabilize or improve vision. Older options (laser photocoagulation, photodynamic therapy with verteporfin) are rarely used now. - Low-vision rehabilitation for advanced disease.

**High-yield board associations and differentials** - Most common cause of irreversible blindness in elderly in developed countries. - Drusen = hallmark finding. Dry = atrophy, wet = neovascularization (VEGF). - Contrast with: diabetic retinopathy (microaneurysms, neovascularization, hemorrhages in diabetics), central retinal artery occlusion (sudden painless monocular vision loss, cherry-red spot), central retinal vein occlusion ("blood and thunder" fundus), retinal detachment (flashes, floaters, curtain-like field loss), cataract (gradual blurring, lens opacity, preserved red reflex loss), glaucoma (peripheral vision loss first, optic disc cupping). - Complications of intravitreal injections: endophthalmitis, retinal detachment, increased intraocular pressure. - Wet AMD is an ophthalmologic urgency: new metamorphopsia warrants prompt referral.