Macular Degeneration — Presentation, Aetiology, Diagnosis, Treatment and Prevention

Macular Degeneration — Presentation, Aetiology, Diagnosis, Treatment and Prevention Definition and anatomical basis

Age-related macular degeneration (AMD) is degeneration of the macula — the area of the retina lying at the posterior pole of the globe, which is the site of highest visual acuity — producing progressive loss of central vision with preservation of peripheral vision.

The macula depends entirely on the choriocapillaris for nutrition. Any disturbance in the vessel wall of the choroidal capillaries, in the permeability or thickness of Bruch's membrane, or in the retinal pigment epithelium, interferes with the exchange of nutrients and oxygen from the choroidal blood to the central retina. Such disturbances occur frequently in older patients.

AMD is one of the most frequent causes of visual loss in older adults and is the commonest cause of legal blindness (20/200 or worse); Framingham Eye Study prevalence was 28% at ages 75–85, with a higher rate in women than in men.

Modifiable and non-modifiable risks: older age, family history of the disorder, cigarette smoking, low dietary intake or low plasma concentrations of antioxidant vitamins and zinc, and white race (for "wet" lesions). High lifetime exposure to sunlight is also a risk factor, as are obesity and hypertension.

AMD is caused by the interplay of genetic predisposition and exposure to modifiable risk factors. Two susceptibility genes have been identified — CFH (complement factor H) and LOC387715/ARMS2.

Carrying the susceptibility allele of either gene increases risk three- to eightfold; having two copies of the susceptibility alleles in both genes increases the risk 50-fold. The combined effect of these polymorphisms carries an attributable risk of 60%. Cigarette smoking and obesity multiply the risks associated with these variants.

The central role of complement factor H identifies complement dysregulation and chronic low-grade inflammation as the pathogenic core — the rationale for modern complement-inhibitor therapy.

Dry (non-exudative, atrophic) AMD — 85–90% of cases. Early and intermediate stages show drusen and pigmentary change. In the geographic atrophy form there are areas of depigmentation alternating with zones of hyperpigmentation, caused mainly by changes in the retinal pigment epithelium; in another form the degeneration involves Bruch's membrane, producing pigmentation of well-circumscribed, roundish yellow areas. As lesions coalesce and involve the central macula, there is progressive worsening of vision to legal blindness.

Wet (exudative, neovascular) AMD — 10–15% of cases, but responsible for most severe visual loss. There is acute exudative pathology as a consequence of neovascularisation — choroidal neovascular membranes breaching Bruch's membrane, with subretinal fluid, haemorrhage, lipid exudate and eventual disciform scarring.

Symptoms: gradual (dry) or rapid (wet) painless loss of central vision; metamorphopsia — straight lines appearing wavy or bent, the earliest and most characteristic symptom of wet AMD; a central scotoma; difficulty reading and recognising faces; reduced contrast sensitivity; need for brighter light; and micropsia. Peripheral vision and navigational vision are preserved — patients never become totally blind from AMD.

Ophthalmoscopic findings vary and do not always parallel the loss of vision — a key clinical caution.

Visual acuity (distance and near) and an Amsler grid for metamorphopsia and central scotoma — also used for home self-monitoring with instructions to report new distortion urgently.

Dilated fundoscopy and slit-lamp biomicroscopy: hard and soft drusen, RPE mottling and clumping, geographic atrophy, subretinal fluid, haemorrhage, hard exudate, and disciform scar.

Optical coherence tomography (OCT) is the current standard for detecting intraretinal and subretinal fluid, pigment epithelial detachment, and drusen volume — it guides initiation, retreatment and extension of anti-VEGF therapy.

Fundus fluorescein angiography defines classic and occult choroidal neovascular membranes; indocyanine green angiography is required to diagnose polypoidal choroidal vasculopathy, which is far commoner in Indian and other Asian eyes.

OCT angiography gives non-invasive detection of neovascularisation including subclinical (non-exudative) CNV; fundus autofluorescence is used to measure and monitor geographic atrophy lesion area.

Dry/intermediate AMD — AREDS2 antioxidant supplementation: vitamin C, vitamin E, zinc, copper, plus lutein and zeaxanthin (which replaced β-carotene because of increased lung cancer risk in smokers). It reduces progression to advanced AMD by roughly 25% over 5 years in patients with intermediate AMD or with advanced AMD in one eye. It does not prevent AMD in those who do not have it, and Cochrane reviews find no benefit for cataract prevention.

Wet AMD — intravitreal anti-VEGF injection is the standard of care: ranibizumab, bevacizumab (off-label but far cheaper; the CATT trial showed it equivalent to ranibizumab), aflibercept, brolucizumab and faricimab. Typically three monthly loading doses followed by a treat-and-extend or pro-re-nata regimen guided by OCT.

Older modalities — photodynamic therapy with verteporfin and thermal laser photocoagulation — are now largely superseded, retained for polypoidal choroidal vasculopathy and selected extrafoveal lesions.

Visual rehabilitation is an important part of therapy for AMD. Patients may benefit from reading glasses or magnification devices — refer all patients with AMD for visual rehabilitation. Add high-intensity task lighting without glare, large print, eccentric viewing training, high-contrast markings and home hazard modification.

Clinical depression may occur as a consequence of reductions in quality of life and should be treated. Screen actively; also recognise Charles Bonnet syndrome.

Smoking cessation is the single most important modifiable intervention — smoking both causes AMD and multiplies genetic risk.

Sunlight protection with ultraviolet-blocking sunglasses and a wide-brimmed hat, given high lifetime sunlight exposure as a risk factor.

Diet rich in dark green leafy vegetables (lutein and zeaxanthin) and oily fish (omega-3), with control of obesity, hypertension and dyslipidaemia.

Amsler grid self-monitoring of the fellow eye with clear instructions to report new distortion immediately, plus regular dilated fundus examination — the second eye is at high risk once one eye is affected.

Prognosis: dry AMD progresses slowly over years; untreated wet AMD causes severe central visual loss within weeks to months, which makes urgent referral for anti-VEGF therapy essential.