macular degeneration

**Definition:** Progressive degenerative disease of the macula (the central retina, with the fovea at its center and the highest cone density), producing loss of central vision with preserved peripheral vision.

**Risk factors:** Age (strongest), smoking (strongest modifiable risk factor), family history, White race, female sex, cardiovascular disease/hypertension, obesity. Genetic associations: complement factor H (CFH) and ARMS2/HTRA1 variants.

**Pathophysiology:** - Dysfunction of the retinal pigment epithelium (RPE) and Bruch membrane, with chronic oxidative stress and complement-mediated inflammation. - **Drusen** (yellow extracellular deposits of lipids and proteins between the RPE and Bruch membrane) are the hallmark. - **Dry (non-neovascular, atrophic) AMD (~85–90%):** Drusen accumulate, then RPE and photoreceptors atrophy slowly. In advanced disease this appears as geographic atrophy. - **Wet (neovascular, exudative) AMD (~10–15%):** VEGF-driven choroidal neovascularization grows through Bruch membrane into the subretinal space. The new vessels are fragile and leak fluid or blood. It causes most cases of severe vision loss and progresses faster.

**Clinical features:** - Painless, gradual central vision loss (dry) or **sudden** central vision loss (wet). - **Metamorphopsia** (straight lines look wavy or distorted, seen on an Amsler grid), central scotoma, difficulty reading and recognizing faces, and decreased contrast sensitivity. - Peripheral vision is preserved, so patients do not go completely blind.

**Diagnosis:** - Dilated fundoscopy shows drusen, RPE changes, geographic atrophy, or subretinal hemorrhage/fluid. - Optical coherence tomography (OCT) shows subretinal or intraretinal fluid in wet AMD. - Fluorescein angiography shows leakage from choroidal neovascularization. - Amsler grid is used for monitoring.

**Management:** - **Dry AMD:** No cure. AREDS2 supplementation (vitamin C, vitamin E, zinc, copper, lutein, and zeaxanthin) slows progression in intermediate or advanced disease. Smoking cessation. Complement inhibitors (pegcetacoplan, avacincaptad pegol) are FDA-approved for geographic atrophy. - **Wet AMD:** **Intravitreal anti-VEGF** injections (bevacizumab, ranibizumab, aflibercept, faricimab) are first-line. Laser photocoagulation and photodynamic therapy are rarely used now.

**High-yield board points:** - AMD is the most common cause of irreversible blindness in older adults in developed countries. - Central vision is lost and peripheral vision is spared, which contrasts with glaucoma (peripheral loss first) and retinitis pigmentosa (night blindness and tunnel vision). - Drusen = dry AMD. Neovascularization with hemorrhage = wet AMD. - Don't confuse AMD with diabetic retinopathy (also treated with anti-VEGF). Diabetic retinopathy causes microaneurysms, hemorrhages, and exudates. - Stargardt disease is a juvenile macular dystrophy (ABCA4 mutation, autosomal recessive). - Anti-VEGF adverse effects: endophthalmitis, retinal detachment, and increased intraocular pressure.