Age-Related Macular Degeneration (AMD)
Central retinal degeneration — dry (atrophic) and wet (neovascular) forms; leading cause of central vision loss in older adults.
Also known as: AMD, age-related macular degeneration, dry AMD, wet AMD, neovascular AMD, geographic atrophy, ARMD
Overview
Progressive degenerative disease of the macula characterized by drusen, retinal pigment epithelial (RPE) changes, and ultimately loss of photoreceptors and central vision. Dry (non-exudative, atrophic) AMD comprises ~85-90% of cases; wet (neovascular, exudative) AMD is defined by choroidal neovascularization (CNV) and accounts for most severe vision loss.
Epidemiology
Leading cause of irreversible central vision loss in adults >50 in industrialized countries. Prevalence rises sharply with age — ~10% by 60, ~30% by 75. Whites of European ancestry are most affected.
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Age-Related Macular Degeneration (AMD) outline — plus all 514 diagnoses, 5,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Risk factors
- Age >50 (most important)
- White (European) ancestry
- Family history of AMD; CFH and ARMS2 polymorphisms
- Cigarette smoking — modifiable, dose-dependent
- Cardiovascular risk factors: hypertension, dyslipidemia, atherosclerosis
- Obesity
- Diet low in antioxidants/leafy greens; high in saturated fat
- Chronic sunlight (UV/blue light) exposure
- Female sex
Pathophysiology
Accumulation of extracellular debris (drusen — lipid- and protein-rich material) between RPE and Bruch membrane impairs metabolic exchange of photoreceptors. Oxidative stress, complement dysregulation (CFH variants), and mitochondrial dysfunction drive RPE loss and photoreceptor degeneration → geographic atrophy in late dry AMD. In wet AMD, choroidal vessels proliferate through Bruch membrane in response to VEGF, forming choroidal neovascularization that leaks fluid and blood beneath the retina → subretinal fluid, hemorrhage, and ultimately disciform scar.
Clinical presentation
Symptoms
- Dry AMD: gradual painless central blurring, difficulty reading, central scotomas; often asymptomatic early
- Wet AMD: SUDDEN-onset central distortion (metamorphopsia — straight lines look wavy), central scotoma, or decline in vision over days to weeks
- Patients describe missing letters in words or distortion seen on Amsler grid testing
- Peripheral vision is preserved
Signs / physical exam
- Drusen on dilated fundus exam — hard (small, discrete) or soft (large, confluent, indistinct borders)
- RPE changes — pigmentary mottling, hyperpigmentation, hypopigmentation
- Geographic atrophy (late dry AMD) — sharply demarcated areas of RPE loss with visible choroidal vessels
- Wet AMD: subretinal hemorrhage, exudates, subretinal fluid, RPE detachment, gray-green CNV membrane, disciform scar
- Amsler grid: distortion, missing areas (central scotoma)
- Reduced visual acuity
Classic findings
Drusen on fundoscopy in dry AMD; sudden metamorphopsia with subretinal fluid and hemorrhage in wet AMD.
Differential diagnosis
- Diabetic macular edema — Known diabetes, dot-blot hemorrhages, exudates, fluid on OCT; anti-VEGF and/or laser
- Central serous chorioretinopathy — Younger men, steroid exposure, type A personality; focal serous detachment on OCT
- Cataract — Generalized blur and glare without metamorphopsia; lens opacity
- Macular hole — Sudden central scotoma; full-thickness hole on OCT
- Epiretinal membrane — Distortion; cellophane reflex on macula; OCT confirms
- Stargardt disease / inherited macular dystrophy — Young onset, family history, electrophysiology
- Polypoidal choroidal vasculopathy — Asian patients, recurrent serosanguineous detachments; ICG angiography
Diagnostic workup
Labs
- Not routinely indicated for diagnosis
Imaging
- Dilated fundus examination
- Optical coherence tomography (OCT) — primary imaging modality; detects intraretinal/subretinal fluid, drusen, RPE elevation, geographic atrophy
- OCT angiography (OCTA) — non-invasive detection of CNV
- Fluorescein angiography — gold standard for CNV; defines lesion type (classic vs occult)
- Indocyanine green angiography — for polypoidal lesions
- Amsler grid for monitoring distortion at home
- Fundus autofluorescence — assesses geographic atrophy
Diagnostic algorithm
| Feature | Dry (Non-exudative) AMD | Wet (Neovascular) AMD |
|---|---|---|
| Prevalence | ~85-90% of AMD | ~10-15% of AMD; majority of severe vision loss |
| Onset of vision loss | Gradual over years | Sudden over days to weeks |
| Hallmark finding | Drusen, RPE changes, geographic atrophy | Choroidal neovascularization with fluid/hemorrhage |
| Key symptom | Central blurring, scotoma | Metamorphopsia, acute central scotoma |
| First-line treatment | AREDS2 (if intermediate/advanced), lifestyle, smoking cessation | Intravitreal anti-VEGF (ranibizumab, bevacizumab, aflibercept, faricimab) |
| Late-stage therapy | Complement inhibitors (pegcetacoplan, avacincaptad) for GA; low-vision aids | Continued anti-VEGF; low-vision rehabilitation |
Treatment
First-line
- Smoking cessation — modifiable risk factor with strongest evidence
- Mediterranean-style diet rich in leafy greens, fish (omega-3), and colored fruits
- Cardiovascular risk factor management (blood pressure, lipids, weight)
- UV protection with sunglasses
- Amsler grid self-monitoring for new distortion → urgent ophthalmology if change
- AREDS2 supplementation for intermediate or advanced dry AMD in one eye: vitamin C 500 mg, vitamin E 400 IU, zinc 80 mg (or lower 25 mg formulation), copper 2 mg, lutein 10 mg, zeaxanthin 2 mg — replaces beta-carotene from original AREDS (lung cancer risk in smokers)
- Do NOT use AREDS2 in early AMD (no benefit) and avoid beta-carotene formulation in smokers
Second-line / adjunct
- Wet AMD — intravitreal anti-VEGF — ranibizumab, bevacizumab (off-label, equivalent efficacy per CATT/IVAN), aflibercept, brolucizumab, faricimab — typically monthly loading then treat-and-extend; mainstay of therapy
- Photodynamic therapy with verteporfin — rarely used today, reserved for polypoidal CNV
- Thermal laser photocoagulation — only for select extrafoveal CNV; largely supplanted by anti-VEGF
- Geographic atrophy (late dry AMD) — complement inhibitors approved by FDA: intravitreal pegcetacoplan (C3 inhibitor) and avacincaptad pegol (C5 inhibitor) slow progression of GA
- Low-vision rehabilitation — magnifiers, eccentric viewing training, audio resources
- Implantable telescope or augmented-reality devices in selected end-stage cases
Complications
- Irreversible central vision loss; legal blindness if bilateral
- Conversion of dry to wet AMD (Amsler grid surveillance is for this)
- Disciform scar — end-stage wet AMD with severe permanent central scotoma
- Fall risk, loss of independence, depression
- Endophthalmitis (~1 per 2,000-5,000) and intraocular pressure spikes from intravitreal injections
PANCE pearls
- Dry AMD = drusen + RPE changes ± geographic atrophy; wet AMD = choroidal neovascularization with fluid, hemorrhage, or exudates.
- SUDDEN metamorphopsia in an older patient with AMD = wet AMD until proven otherwise — urgent referral for anti-VEGF.
- AREDS2 is for INTERMEDIATE OR ADVANCED dry AMD in one eye, not early AMD; replaces beta-carotene because of lung cancer risk in smokers (CARET trial).
- Anti-VEGF (ranibizumab, bevacizumab, aflibercept, faricimab) revolutionized wet AMD — CATT showed bevacizumab equivalent to ranibizumab.
- Hand Amsler grids to AMD patients and instruct to check each eye daily and report new distortion or scotoma.
- Newer complement inhibitors (pegcetacoplan, avacincaptad) slow geographic atrophy progression but do not restore vision.
References
- AAO 2019 — American Academy of Ophthalmology. Age-Related Macular Degeneration Preferred Practice Pattern. Ophthalmology 2020;127(1):P1-P65
- AREDS — AREDS Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration. Arch Ophthalmol 2001;119(10):1417-1436
- AREDS2 — AREDS2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration. JAMA 2013;309(19):2005-2015
- CATT — CATT Research Group. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. NEJM 2011;364(20):1897-1908
- IVAN — IVAN Study Investigators. Ranibizumab versus bevacizumab to treat neovascular AMD: 2-year findings. Lancet 2013;382(9900):1258-1267
Practice EENT questions on FirstPassPA
Turn this outline into retention. 5,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Start studying free → Browse all 514 diagnosesEducational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.