Neovascular Age-Related Macular Degeneration

Advanced (wet or exudative) age-related macular degeneration in which abnormal blood vessels grow from the choroid (choroidal neovascularisation) into the sub-retinal pigment epithelial or subretinal space, causing leakage, haemorrhage, and fibrous scarring.

• Driven by VEGF. Risk factors: age over 55 years, smoking (2 to 3 times higher risk), family history, CFH and ARMS2 variants, white ancestry, obesity and cardiovascular disease.
• Accounts for 10 to 15 percent of age-related macular degeneration but about 80 to 90 percent of severe vision loss from the disease.
• Types of neovascularisation: type 1 (occult, under the retinal pigment epithelium), type 2 (classic, subretinal), type 3 (retinal angiomatous proliferation, intraretinal origin), and polypoidal choroidal vasculopathy (more common in Asian and African populations, with polyps and branching vascular network, often with large haemorrhages).
• Untreated, vision falls to 6/60 or worse within 1 to 2 years, and the fellow eye develops disease in about 10 to 12 percent per year.

• Rapid onset (days to weeks) of metamorphopsia (straight lines appear wavy), central scotoma, blurred reading vision, and reduced acuity.
• Fundus: grey-green subretinal lesion, subretinal or intraretinal haemorrhage, hard exudates, retinal pigment epithelial detachment, subretinal fluid, and in the end stage a disciform scar.
• Polypoidal disease: orange nodules, serous or haemorrhagic pigment epithelial detachments, and massive subretinal or vitreous haemorrhage.
• Fellow-eye findings: drusen and pigment changes.

• Visual acuity, Amsler grid, dilated fundus examination.
• Optical coherence tomography (key test): subretinal fluid, intraretinal cysts, pigment epithelial detachment, subretinal hyper-reflective material, and thickness for monitoring.
• Optical coherence tomography angiography: shows the neovascular network without dye; fluorescein angiography (classic leakage, occult late leakage), indocyanine green angiography (polypoidal lesions and retinal angiomatous proliferation).
• Same-week referral for suspected conversion, with treatment within 1 to 2 weeks of diagnosis.

• Intravitreal anti-VEGF therapy is first-line, given under aseptic conditions (povidone-iodine 5 percent, topical anaesthesia, speculum, 3.5 to 4 mm from limbus with a 30 gauge needle):
  • Ranibizumab 0.5 mg in 0.05 mL; bevacizumab 1.25 mg in 0.05 mL (off-label, widely used); aflibercept 2 mg in 0.05 mL (or 8 mg high-dose with longer intervals); faricimab 6 mg in 0.05 mL (anti-VEGF and anti-angiopoietin-2); brolucizumab 6 mg in 0.05 mL (risk of intraocular inflammation and retinal vasculitis, monitor).
  • Regimen: loading phase of three monthly injections (four for aflibercept 2 mg: three monthly then every 8 weeks; faricimab up to four monthly), followed by a treat-and-extend protocol (extend by 2 weeks if the macula is dry, up to 12 to 16 weeks; shorten by 2 weeks if fluid recurs) or as-needed treatment guided by optical coherence tomography.
  • Expected result: about 90 percent keep vision (lose fewer than 15 letters), 30 to 40 percent gain 15 letters or more.
• Polypoidal choroidal vasculopathy: anti-VEGF with or without photodynamic therapy using verteporfin (6 mg/m2 IV over 10 minutes, laser at 15 minutes, 83 seconds, 50 J/cm2) for polyp regression.
• Submacular haemorrhage threatening the fovea: intravitreal tissue plasminogen activator 25 to 50 micrograms with expansile gas (14 percent perfluoropropane or 20 percent sulphur hexafluoride) and face-down positioning, plus anti-VEGF.
• Poor response (persistent fluid after 3 to 6 injections): change the agent, shorten the interval, or add photodynamic therapy; consider tachyphylaxis.
• Adverse effects: endophthalmitis (about 1 in 2000 to 3000 injections), intraocular pressure spike, subconjunctival haemorrhage, retinal pigment epithelial tear (with large pigment epithelial detachments), cataract, geographic atrophy progression, and rare arterial thromboembolic events.
• Follow-up: monthly assessment during loading; patient self-testing; lifelong monitoring; supplements and smoking cessation; low-vision aids; registration for visual impairment.