Extracts from "Clinical Evidence": Age related macular degeneration

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Background Definition Age related macular degeneration is the late stage of age related maculopathy. It has two forms: atrophic (or dry), characterised by geographic atrophy, and exudative (or wet), characterised by choroidal neovascularisation, which eventually causes a disciform scar. 1 2 Interventions Beneficial: Thermal laser photocoagulation Photodynamic treatment with verteporfin Unknown effectiveness: Proton beam and scleral plaque radiotherapy Submacular surgery Unlikely to be beneficial: External beam radiation Ineffective or harmful Subcutaneous interferon alfa-2a Incidence/prevalence Age related macular degeneration is the commonest cause of blind registration in industrialised countries. The atrophic form is more common than the more sight threatening exudative form, affecting about 85% of people with age related macular degeneration.3 End stage (blinding) age related macular degeneration is found in about 1.7% of all people aged over 50, and incidence rises with age (0.7-1.4% in people aged 65-75, 11.0-18.5% in people aged over 85).4-6 Aetiology/risk factors The aetiology is multifactorial. Age is the strongest risk factor. Ocular risk factors for the development of exudative age related macular degeneration include the presence of soft drusen, macular pigmentary change, and choroidal neovascularisation in the other eye. Systemic risk factors are hypertension, smoking, and positive family history. 7 8 A role for diet and exposure to ultraviolet light is suspected but unproved. Prognosis Age related macular degeneration impairs central vision, which is required for reading, driving, face recognition, and all fine visual tasks. Atrophic age related macular degeneration progresses slowly over many years, and time to legal blindness (visual acuity <20/200) is highly variable (usually about 5–10 years). 9 10 Exudative age related macular degeneration is more threatening to vision and is responsible for 90% of severe visual loss in people with age related macular degeneration. It usually manifests with a sudden worsening and distortion of central vision. It progresses rapidly (typically over weeks or months) until scarring is complete and no further vision is lost, at which point legal blindness has usually been reached. Most people (estimates vary from 60% to 90%) with exudative age related macular degeneration progress to legal blindness and develop a central defect (scotoma) in the visual field.11-14 Peripheral vision is preserved, allowing the person to be mobile and independent. The ability to read with visual aids depends on the size and density of the central scotoma and the degree to which the person retains sensitivity to contrast. Once exudative age related macular degeneration has developed in one eye, the other eye is at high risk (cumulative estimated incidence 10% at one year, 28% at three years, and 42% at five years).7 Aims To minimise loss of visual acuity and central vision; to preserve the ability to read with or without visual aids; to optimise quality of life; to minimise adverse effects of treatment. Outcomes Visual acuity, rates of legal blindness, contrast sensitivity, quality of life, appearance of retina on fluorescein angiography, rate of adverse effects of treatment. Visual acuity is measured using special eye charts, usually the early treatment of diabetic retinopathy study (ETDRS) chart, although many studies do not specify which chart was used. Stable vision is usually defined as loss of two lines or less on the ETDRS chart. Moderate and severe visual loss are defined as a loss of more than three and six lines respectively, corresponding to a doubling and quadrupling of the vision angle. Loss of vision to legal blindness (<20/200) is also used as an outcome. A reading of 20/200 (or 6/60 in metric) on the Snellen chart means that a person can see at 20 yards (or 6 metres) what a normally sighted person can see at 200 yards (or 60 metres). Methods Clinical Evidence search and appraisal December 1999. All randomised controlled trials (RCTs) were included, but small early RCTs were excluded when larger, more recent trials were available. Question: What are the effects of treatments for exudative age related macular degeneration? Option: Thermal laser photocoagulation Summary Four large RCTs have found that laser photocoagulation decreases the rate of severe visual loss and preserves contrast sensitivity in selected people with exudative age related macular degeneration (those with well demarcated lesions). Choroidal neovascularisation recurs within two years in about half of those treated. Photocoagulation may reduce visual acuity initially. Benefits We found no systematic review. Versus no treatment: We found four large unblinded multicentre RCTs of laser photocoagulation versus no treatment in a selected population.11-17 We also found four smaller RCTs that included a wider range of people.18-21 All four of the large trials found that treatment conferred clinically and statistically significant benefit, in terms of reduced risk of severe visual loss (defined as loss of six or more lines on the special eye chart), which persisted beyond three years. Participants differed in terms of the position of the choroidal neovascularisation on the retina, whether far, near, or under the centre of fixation (extrafoveal, 11 13 juxtafoveal, 14 15 or subfoveal 12 16 17). In the study of extrafoveal choroidal neovascularisation, treatment was beneficial despite the fact that 19% of eyes randomised to observation later received laser treatment. 13 11 Reanalysis of people with juxtafoveal choroidal neovascularisation found that benefit was limited to those with pure classic lesions (no occult element) on fluorescein angiography (52% of randomised eyes), who were more than twice as likely to avoid developing severe visual loss than were people receiving no treatment (odds ratio 2.2, 95% confidence interval 1.4 to 3.4 at three years). The two trials in people...