Macular Degeneration — Symptoms, Causes & Treatment | MyMedicPlus

Age-related macular degeneration (AMD) is a progressive degenerative disease of the macula — the central 5mm region of the retina containing the highest concentration of cone photoreceptors responsible for fine detail vision, colour perception, and facial recognition. AMD is the leading cause of irreversible central vision loss in adults over 50, affecting approximately 200 million people worldwide, with prevalence projected to reach 300 million by 2040 as the global population ages. AMD is classified into two major forms: dry AMD (atrophic or non-neovascular AMD), which accounts for 85-90% of cases and progresses slowly through accumulation of drusen (extracellular deposits beneath the retinal pigment epithelium, RPE) and gradual RPE and photoreceptor atrophy; and wet AMD (neovascular AMD), which represents 10-15% of cases but is responsible for 90% of severe vision loss, caused by growth of abnormal choroidal neovascularisation (CNV) beneath the retina leaking fluid and blood. Geographic atrophy is the advanced form of dry AMD — characterised by confluent areas of RPE and choriocapillaris loss causing irreversible central scotoma. Both dry and wet AMD are graded using the AREDS classification system (categories 1-4) which guides treatment decisions and risk stratification.

Age is the strongest risk factor for AMD — prevalence increases from approximately 2% in adults aged 50-59 to over 35% in those aged 75 and above. Smoking is the most important modifiable risk factor, doubling to tripling the risk of AMD compared with never-smokers; former smokers retain elevated risk for years after cessation. Genetic susceptibility is substantial: complement factor H (CFH) polymorphism (Y402H) confers a 2-4x increased risk through impaired complement regulation leading to chronic low-grade inflammation of Bruch's membrane; ARMS2/HTRA1 variants on chromosome 10q26 are the second major genetic locus. Together, CFH and ARMS2 variants explain approximately 50% of the population-attributable genetic risk. Female sex, Caucasian and Chinese ethnicity, family history of AMD (3-5x increased risk in first-degree relatives), hypertension, hypercholesterolaemia, obesity, and cardiovascular disease are additional risk factors. Diets high in saturated fat and low in lutein, zeaxanthin, and omega-3 fatty acids are associated with higher AMD risk. High-energy light exposure, including sunlight and blue-light, contributes to cumulative oxidative retinal injury.

AMD exclusively affects central vision while sparing peripheral vision throughout the disease course — patients are never completely blind from AMD alone. Dry AMD progresses insidiously over years: early symptoms include subtle blurring or loss of sharpness when reading fine print, difficulty adjusting to low light levels (dark adaptation impairment), and mild colour perception changes. As drusen coalesce and geographic atrophy progresses, patients notice a gradually enlarging central grey or dark area (scotoma) in vision and increasing difficulty reading without magnification. Wet AMD typically presents more acutely, often developing over days to weeks: the cardinal symptom is metamorphopsia — distortion of straight lines (doorframes, printed text, window frames appearing bent or wavy), which the patient notices by looking at the Amsler grid (a square grid pattern used for home monitoring). Central scotoma (a dark, blurred, or absent area in the centre of vision) may appear or worsen suddenly. Visual acuity can drop precipitously — from 6/12 to 6/60 or worse within weeks if untreated — as subretinal fluid, haemorrhage, and fibrovascular membrane formation occur. Patients frequently notice difficulty recognising faces even at close range and are unable to read normal print.

Dilated slit-lamp fundus examination is the initial assessment, revealing characteristic signs: soft drusen (large, poorly defined yellowish deposits beneath the RPE — intermediate AMD), pigmentary changes (areas of hyperpigmentation and depigmentation), subretinal fluid or haemorrhage (wet AMD), and confluent RPE loss with pale atrophic areas (geographic atrophy, advanced dry AMD). Optical coherence tomography (OCT) is the single most important diagnostic investigation: non-invasive cross-sectional imaging of the macula with micron-resolution detects subretinal fluid, intraretinal fluid, sub-RPE fluid, drusenoid RPE detachment, and degree of atrophy — enabling same-day diagnosis of wet AMD conversion and monitoring of anti-VEGF treatment response. OCT-angiography (OCTA) visualises choroidal neovascularisation and the CNV network in detail without fluorescein injection. Fluorescein angiography (FFA) maps the CNV lesion, its type (classic vs occult), and fluorescein leakage patterns — useful for treatment planning. Indocyanine green angiography (ICGA) provides superior choroidal imaging for polypoidal choroidal vasculopathy (PCV) — a wet AMD variant more prevalent in Asian populations. Amsler grid self-monitoring — the patient fixates the central dot with each eye separately and checks for new distortion, missing areas, or waviness — is a validated home tool for detecting early wet AMD conversion.

Wet AMD treatment is centred on intravitreal anti-VEGF (vascular endothelial growth factor) injections delivered directly into the vitreous cavity under topical anaesthesia with a fine needle, inhibiting pathological CNV growth and reducing retinal oedema. Approved anti-VEGF agents include ranibizumab (Lucentis, 0.5mg), bevacizumab (Avastin, 1.25mg — off-label but cost-effective), aflibercept (Eylea, 2mg), and the newer bispecific antibody faricimab (Vabysmo, 6mg), which targets both VEGF-A and Ang-2 allowing extended treatment intervals up to every 16 weeks. Treat-and-extend or pro re nata (PRN — as needed) regimens personalise injection frequency after loading doses. Anti-VEGF treatment stabilises or improves vision in approximately 90% of wet AMD patients; 30-40% experience clinically meaningful visual improvement (gain of 15 or more ETDRS letters). Geographic atrophy (advanced dry AMD): pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay), both complement inhibitors, are FDA-approved (2023) and slow geographic atrophy growth rate by 17-22% annually — the first approved treatments for this form. Intermediate dry AMD (AREDS2 category 3): daily supplementation with AREDS2 formula (lutein 10mg + zeaxanthin 2mg + vitamin C 500mg + vitamin E 400 IU + zinc 80mg + copper 2mg) reduces progression risk by 25% over 5 years.

Untreated wet AMD leads within months to subfoveal disciform scarring — an irreversible fibrovascular membrane replacing the foveal architecture and causing permanent severe central visual acuity loss typically to 6/60 or worse (legal blindness in most jurisdictions). Bilateral AMD causes profound visual disability: inability to drive (revocation of driving licence), loss of ability to read standard print without magnification, difficulty recognising faces, inability to perform fine visual tasks, and increasing dependence on others. Depression affects 30-40% of patients with significant vision loss from AMD — underscreened and undertreated in ophthalmological settings. Social isolation and loss of independence are strongly associated with bilateral AMD. Intravitreal injection complications, though uncommon, include endophthalmitis (serious intraocular infection occurring in approximately 1 in 2,000-5,000 injections), rhegmatogenous retinal detachment, vitreous haemorrhage, and traumatic cataract. Submacular haemorrhage from wet AMD can cause acute severe vision loss and requires urgent referral — pneumatic displacement with subretinal tissue plasminogen activator may preserve vision if performed within 2-3 weeks. Falls and hip fractures are significantly more common in AMD patients with severe visual loss.

Quit smoking immediately — it is the most modifiable risk factor. Wear UV-protective sunglasses, maintain healthy weight and blood pressure, eat dark leafy vegetables rich in lutein and zeaxanthin, and exercise regularly. Regular dilated eye examinations annually after age 50 enable early detection. AREDS2 supplementation for intermediate AMD. Quit smoking immediately — it is the most important modifiable risk factor for AMD; smoking doubles to triples the risk, and former smokers retain elevated risk for years after cessation, making cessation at any age beneficial. Maintain UV protection with wraparound UV400 sunglasses and wide-brimmed hats outdoors to limit cumulative photochemical retinal oxidative damage. Eat a diet rich in lutein and zeaxanthin (kale, spinach, egg yolks), omega-3 fatty acids (oily fish twice weekly — salmon, mackerel, sardines), and antioxidants (coloured vegetables and fruits) — dietary patterns associated with lower AMD incidence. Maintain healthy weight, control blood pressure (target below 130/80 mmHg), and manage cardiovascular risk factors — obesity and hypertension are independent risk factors for AMD progression. AREDS2 daily supplementation (lutein 10 mg + zeaxanthin 2 mg + vitamin C 500 mg + vitamin E 400 IU + zinc 80 mg + copper 2 mg) reduces progression from intermediate to advanced AMD by 25% over 5 years — recommended for AREDS category 3 patients only. Regular aerobic exercise (150 minutes weekly) may reduce AMD risk through improved choroidal circulation. Annual dilated fundus examination by an optometrist from age 50 (or any age with family history or multiple risk factors) enables early detection. Use the Amsler grid daily at home to self-monitor for new distortion — each eye separately, reporting any new waviness or missing areas to your ophthalmologist promptly.

Seek same-day urgent ophthalmological assessment (call your local eye emergency service or hospital eye department) for: sudden onset of visual distortion — straight lines appearing wavy or bent (metamorphopsia) — as this is a key symptom of wet AMD and requires same-day assessment and treatment initiation with anti-VEGF injections; sudden new visual loss or a central grey or black spot appearing in vision (scotoma); or rapid deterioration of vision that was previously stable in a person with known AMD. Vision changes occurring in hours to days are urgent — anti-VEGF injections (ranibizumab, aflibercept, bevacizumab) for wet AMD are most effective the sooner they are given after new neovascularisation develops. See an optometrist for: annual dilated fundus examination for all people aged 50 and above with a family history of AMD; any gradual vision changes, difficulty with night vision, or noticing blind spots in central vision — the Amsler grid can be used at home to self-monitor for new distortion. Regular optometry review as directed by your ophthalmologist is essential for monitoring dry AMD progression.