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Macular Degeneration, Age-Related (AMD)

Authors: Richard W. Allinson, MD; Hunter Grey, OD

BASICS

DESCRIPTION

  • Leading cause of vision loss in elderly
  • Two major forms:
  • Atrophic (nonexudative): Drusen, pigment changes
  • Neovascular (exudative, nAMD): Choroidal neovascular membranes (CNVM)

EPIDEMIOLOGY

  • Higher prevalence in Whites
  • Female predominance
  • Prevalence:
  • Age 65–74: 11%
  • Age β‰₯75: 27.9%

ETIOLOGY & PATHOPHYSIOLOGY

Atrophic (Dry) AMD

  • Drusen: Hyaline deposits between RPE and Bruch’s membrane
  • Light exposure leads to RPE dysfunction β†’ impaired debris clearance β†’ drusen accumulation

Neovascular (Wet) AMD

  • Progresses from atrophic stage
  • Type 1 (Occult CNVM): Beneath RPE
  • Type 2 (Classic CNVM): In subretinal space
  • Type 3 (RAPs): Originates from deep capillary plexus
  • Polypoidal choroidal vasculopathy (PCV): Subtype with serosanguineous PEDs

Genetics

  • CFH Y402H polymorphism increases risk

RISK FACTORS

  • Obesity, smoking, C. pneumoniae
  • Family history
  • Sunlight exposure, light iris color
  • Hyperopia, short stature

GENERAL PREVENTION

  • UV protection
  • Routine eye exams

DIAGNOSIS

HISTORY

  • Central vision distortion or blurring
  • Amsler grid distortion

PHYSICAL EXAM

  • Dry AMD: Drusen on fundus exam
  • nAMD:
  • CNVM (choroidal neovascular membrane)
  • Subretinal hemorrhage, exudates, disciform scars
  • PED (Pigment epithelial detachment)

DIFFERENTIAL DIAGNOSIS

  • Diabetic or hypertensive retinopathy
  • Central serous chorioretinopathy
  • Drug-induced maculopathy:
  • Topiramate
  • Pentosan polysulfate sodium

DIAGNOSTIC TESTS

  • Fluorescein angiography (FA): distinguishes dry vs wet
  • Indocyanine green angiography: detects occult CNVMs
  • OCT / SD-OCT / SS-OCT / OCTA:
  • Subretinal fluid
  • Retinal thickness
  • PED characterization

TREATMENT

GENERAL

  • Low-vision aids
  • AREDS supplementation

FIRST LINE - Anti-VEGF Agents

Ranibizumab (Lucentis)

  • 0.5 mg IVI every 4 weeks
  • Improves/maintains vision in 95% over 1 year
  • TER (Treat and Extend Regimen):
  • Extend by 2 weeks per visit if inactive
  • Max: 12-week interval

Aflibercept (Eylea)

  • 2 mg IVI every 4 weeks Γ—12 weeks β†’ every 8 weeks
  • Alternative in nonresponders to ranibizumab

Brolucizumab (Beovu)

  • 6 mg IVI monthly Γ—3 β†’ every 8–12 weeks
  • Smaller molecule, longer interval
  • Caution: Risk of retinal vasculitis and occlusion

Faricimab (Vabysmo)

  • Targets VEGF + angiopoietin-2
  • 6 mg IVI Γ—4 weeks Γ—4 β†’ every 2–4 months
  • FDA-approved for nAMD

SECOND LINE

Bevacizumab (Avastin)

  • 1.25 mg IVI; cost-effective off-label use

Avacincaptad pegol

  • C5 complement inhibitor under investigation for geographic atrophy

SURGICAL/OTHER INTERVENTIONS

  • Photodynamic therapy (PDT): Rarely used now
  • Vitrectomy: For CNVM-related hemorrhage (within 7 days)
  • Subretinal blood displacement:
  • tPA Β± gas bubble
  • Laser photocoagulation: Only for CNVM β‰₯200 ΞΌm from fovea

COMPLEMENTARY & ALTERNATIVE MEDICINE

AREDS 1 (Original Formulation)

  • Vitamin C 500 mg
  • Vitamin E 400 IU
  • Ξ²-carotene 15 mg (avoid in smokers)
  • Zinc oxide 80 mg + copper 2 mg

AREDS 2 (Updated)

  • Remove Ξ²-carotene
  • Add lutein 10 mg + zeaxanthin 2 mg
  • No added benefit from omega-3 FA

ONGOING CARE

FOLLOW-UP & MONITORING

  • Monitor Amsler grid daily
  • If no symptoms β†’ recheck in 6–12 months
  • Stable nAMD on OCT: cataract surgery is safe

DIET

  • Dark green leafy vegetables: Lutein + zeaxanthin
  • Omega-3 rich fish
  • Mediterranean diet: reduces progression (AREDS2 data)

PROGNOSIS

  • Dry AMD with bilateral drusen:
  • 5-year risk of nAMD: ~15%
  • nAMD in one eye:
  • Risk of conversion in fellow eye: 5–14% per year
  • Anti-VEGF therapy:
  • Long-term preserved useful vision in ~20%
  • Not all initial visual gains sustained after 5 years

COMPLICATIONS

  • Irreversible vision loss/blindness
  • Elevated IOP post anti-VEGF injections
  • Disciform scars, PED recurrence

CODES

  • H35.32 – Exudative AMD
  • H35.31 – Nonexudative AMD
  • H35.3290 – Exudative AMD, unspecified eye

CLINICAL PEARLS

  • Patients may describe distorted straight lines
  • Amsler grid is a practical home screening tool
  • AREDS formula reduces progression risk in intermediate or advanced AMD
  • Be vigilant about bilateral involvement risk
  • Anti-VEGF therapy is first-line, especially for subfoveal CNVMs