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Nonexudative (Dry) Age-Related Macular Degeneration

ROUTINE — Retina

Symptoms

  • gradual loss of central vision (months to years)
  • metamorphopsia (distortion on amsler grid)
  • paracentral scotoma
  • reduced contrast sensitivity and difficulty with low-light tasks
  • may be asymptomatic in early stages

Clinical Findings

Drusen characteristics

  • hard drusen: <63 μm, well-defined; low risk of progression
  • soft drusen: ≥63 μm, fuzzy edges; high risk for amd progression
  • large drusen: ≥125 μm (areds high-risk marker)
  • reticular pseudodrusen: subretinal deposits above the rpe; high risk for ga and wet amd

RPE changes

  • rpe mottling, hyperpigmentation, or focal pigment aggregates
  • geographic atrophy (ga): sharply demarcated areas of rpe and photoreceptor loss
  • increased visibility of deep choroidal vessels within atrophic patches

AREDS severity score (5-year risk)

  • 1 point per eye for large drusen; 1 point per eye for pigmentary changes
  • score 0 (0.5% risk) to score 4 (50% risk of advanced amd)

Etiology

Pathophysiology

  • age-related rpe and photoreceptor degeneration
  • accumulation of lipoproteinaceous debris (drusen) in bruch’s membrane

Risk factors

  • age >55, caucasian ethnicity, and family history
  • smoking (primary modifiable risk)
  • genetics: cfh y402h and arms2/htra1 variants

Red Flags

  • conversion to wet amd: new metamorphopsia or sudden scotoma
  • sudden drusen regression: can herald impending cnvm or geographic atrophy
  • ga expansion: hyperautofluorescent borders on faf predict rapid growth

Investigations

Imaging

  • oct: quantify drusenoid ped, geographic atrophy, and hyperreflective foci
  • fundus autofluorescence (faf): track ga expansion and assess border activity
  • near-infrared imaging: best modality for detecting reticular pseudodrusen

Monitoring

  • amsler grid: daily home monitoring for metamorphopsia
  • preferential hyperacuity perimetry (php): e.g., foreseehome for early cnvm detection

Exudative workup (if suspected)

  • urgent oct, ivfa, or octa to rule out choroidal neovascularization (cnv)

Treatment

AREDS2 supplements

  • formula: vit c (500mg), vit e (400iu), zinc (80mg), copper (2mg), lutein (10mg), zeaxanthin (2mg)
  • replaces beta-carotene with lutein/zeaxanthin to avoid lung cancer risk in smokers
  • reduces progression to advanced amd by ~25% in high-risk patients

Geographic atrophy (FDA-approved)

  • pegcetacoplan (syfovre): c3 inhibitor; slows ga growth by 15-20%
  • avacincaptad pegol (izervay): c5 inhibitor
  • note: 2-7% risk of conversion to wet amd; does not improve vision

Lifestyle & support

  • smoking cessation, mediterranean diet, and uv protection
  • low-vision rehabilitation: magnifiers and eccentric viewing training

Clinical Pearl

areds2 vitamins are only for intermediate or advanced amd — prescribing them for small drusen offers no benefit and may give false reassurance.

Differential Diagnosis

  • • cuticular drusen ("stars in the sky")
  • • pattern dystrophy
  • • adult-onset foveomacular vitelliform dystrophy
  • • toxic retinopathies (e.g., chloroquine)
  • • myopic degeneration

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