Dry Age-Related Macular Degeneration

Non-neovascular (atrophic) age-related macular degeneration, accounting for 85 to 90 percent of cases. It is characterised by drusen (extracellular deposits between the retinal pigment epithelium and Bruch membrane), pigmentary change, and, in advanced disease, geographic atrophy (sharply demarcated areas of retinal pigment epithelial and photoreceptor loss).

• Stages: early (medium drusen 63 to 125 micrometres), intermediate (large drusen above 125 micrometres or pigment abnormalities), and late (geographic atrophy involving or threatening the fovea).
• Risk factors: age (above 50 years, prevalence about 10 percent in those over 80), smoking (doubles to quadruples risk), family history, white ancestry, CFH, ARMS2 and HTRA1 genetic variants, cardiovascular disease, obesity, diet low in antioxidants and fish, and sunlight exposure.
• Pathogenesis: oxidative stress, chronic inflammation with complement activation, lipid accumulation, and retinal pigment epithelial dysfunction.
• Progression: about 1 to 2 percent per year conversion to neovascular disease and expansion of atrophy about 1.5 to 2.5 mm2 per year.

• Gradual painless blurred central vision, difficulty reading in dim light, reduced contrast sensitivity, need for brighter light, slow dark adaptation, and metamorphopsia (rare unless neovascular conversion).
• Fundus: yellow-white drusen (hard, soft, and reticular pseudodrusen), retinal pigment epithelial hyper- and hypopigmentation, and central geographic atrophy with visible choroidal vessels.
• Visual acuity may be near normal in early and intermediate disease and falls to 6/60 or worse with foveal atrophy.
• Bilateral but asymmetric; reduced reading speed and face recognition in advanced disease.

• Visual acuity, Amsler grid, dilated fundus examination, and slit lamp biomicroscopy.
• Optical coherence tomography: drusen, drusenoid pigment epithelial detachment, subretinal drusenoid deposits, outer retinal atrophy, and hypertransmission of signal into the choroid; the best test to detect conversion to neovascular disease (subretinal or intraretinal fluid).
• Fundus autofluorescence: area and growth of geographic atrophy (hypoautofluorescent regions), and marginal hyperautofluorescence predicting progression.
• Optical coherence tomography angiography or fluorescein angiography when suspected neovascular conversion.
• Microperimetry and dark adaptation tests in research and low-vision planning.

• Lifestyle: stop smoking, healthy diet with leafy green vegetables, oily fish (two portions per week), Mediterranean-type diet, regular exercise, blood pressure and lipid control, UV-protective sunglasses.
• Nutritional supplements for intermediate disease or advanced disease in one eye (reduces progression to advanced disease by about 25 percent over 5 years): vitamin C 500 mg, vitamin E 400 IU, zinc 80 mg (as zinc oxide) with copper 2 mg, lutein 10 mg and zeaxanthin 2 mg daily (beta-carotene is replaced by lutein and zeaxanthin in smokers and ex-smokers because of lung cancer risk). Supplements do not help early disease and do not reverse established atrophy.
• Geographic atrophy: complement inhibitors given by intravitreal injection slow the growth of atrophy: pegcetacoplan 15 mg in 0.1 mL every 25 to 60 days, or avacincaptad pegol 2 mg in 0.1 mL every month (up to 12 months). Risks include conversion to neovascular disease (about 6 to 12 percent), intraocular inflammation, retinal vasculitis, and endophthalmitis; benefit is slowing, not restoration of vision.
• Monitoring: self-testing with the Amsler grid or digital apps weekly, fundus examination every 6 to 12 months (more often for high-risk features), with urgent assessment within 1 week for new distortion or blurring.
• Low vision rehabilitation: magnifiers, high-contrast materials, task lighting, electronic reading aids, text-to-speech, orientation training, and registration of visual impairment when criteria are met.
• Treat cataract if visually significant; cataract surgery does not worsen progression.
• Counselling on the risk to relatives, no proven benefit of aspirin, statins or omega-3 supplements, and avoid unproven stem cell clinics.
• Photobiomodulation and other emerging therapies are investigational.