Key Facts

AMD affects central vision while peripheral vision is preserved. Early detection of wet AMD and prompt anti-VEGF treatment are critical for preserving vision.

Epidemiology

• ~600,000 people in the UK; leading cause of certified sight impairment
• Prevalence rises sharply after 55: 10% of 65-74; 30% of >75
• Wet AMD causes 90% of severe visual loss from AMD despite being only 10% of cases

Aetiology

• Risk factors: age, smoking (2-3× risk), family history, APOE/CFH gene variants

Pathophysiology

• Drusen: extracellular deposits between RPE and Bruch's membrane; contain complement proteins, lipids; induce inflammation
• Geographic atrophy (dry): progressive loss of RPE and photoreceptors; central scotoma develops

Dry AMD

• Gradual central visual loss (months to years)
• Difficulty reading (small print, newspaper)
• Difficulty recognising faces
• Need for brighter lighting
• Drusen and RPE changes on fundoscopy

Wet AMD

• Rapid central visual loss (days to weeks)
• Metamorphopsia (straight lines appear wavy - Amsler grid positive)
• Central scotoma
• Fundoscopy: subretinal/intraretinal fluid, haemorrhage, grey-green CNV membrane

Red Flags

• Dense central scotoma affecting both eyes → CVI registration, low vision services

Bedside

• Visual acuity (Snellen)
• Amsler grid: metamorphopsia detection (distortion of grid lines)
• Fundoscopy (dilated): drusen, RPE changes, haemorrhage, CNV, atrophy

Bloods

• Not routinely needed

Imaging

• OCT (optical coherence tomography): gold standard for diagnosis and monitoring
  • Drusen, RPE atrophy, intraretinal/subretinal fluid, CNV
• Fundus fluorescein angiography (FFA): identifies CNV type and location
• OCT angiography (OCTA): non-invasive vascular imaging; detects CNV without dye injection
• Fundus autofluorescence (FAF): maps geographic atrophy

Special Tests

• Serial Amsler grid monitoring (dry AMD patients)
• Home monitoring devices (ForeseeHome) in high-risk patients

Non-pharmacological

• Smoking cessation (most important modifiable risk factor)
• Low vision aids: magnifiers, large print, electronic aids, lighting
• CVI registration: when eligible; access to social support
• Amsler grid self-monitoring: for dry AMD patients to detect wet conversion early
• Driving: inform DVLA if visual standards not met

Pharmacological

• Wet AMD - anti-VEGF intravitreal injections (NICE TA155, TA294, TA486):
  • Aflibercept (Eylea) 2mg: loading 3 monthly injections then treat and extend (8-16 weekly)
  • Ranibizumab (Lucentis) 0.5mg: monthly or PRN
  • Faricimab (Vabysmo): bispecific (anti-VEGF + anti-Ang2); longer intervals
  • Brolucizumab: potent but risk of intraocular inflammation
  • Treatment started within 14 days of diagnosis (NICE target)
• Dry AMD:
  • No specific treatment for early dry AMD
  • AREDS2 supplements: for intermediate AMD (vitamins C, E, zinc, copper, lutein, zeaxanthin) - reduce progression risk by 25%
  • Pegcetacoplan (C3 complement inhibitor): FDA-approved for geographic atrophy (emerging; not yet NICE-approved in UK at time of writing)

Surgical/Interventional

• Photodynamic therapy (PDT): verteporfin + laser; now rarely used (superseded by anti-VEGF)
• Submacular surgery: rarely performed; for large submacular haemorrhage (pneumatic displacement + anti-VEGF)

Referral Criteria

• Suspected wet AMD: urgent ophthalmology referral (aim treatment within 14 days)
• Dry AMD with drusen: optometrist monitoring; annual review
• CVI: when eligible for registration

• Dry AMD: slow progression over years; geographic atrophy causes gradual central vision loss; peripheral vision preserved
• Wet AMD (treated): anti-VEGF stabilises or improves vision in ~90%; mean gain of 8-15 letters (ANCHOR/MARINA/VIEW trials)
• Wet AMD (untreated): rapid loss of central vision over weeks-months
• Anti-VEGF treatment is ongoing (often for years); treatment burden is significant
• AREDS2 supplements: reduce progression from intermediate to advanced AMD by 25%
• Vision loss significantly impacts quality of life, independence, and mental health

Classification of AMD

Key Anti-VEGF Trials