Forecasting Age-Related Macular Degeneration Through 2050

Commentary

Age-related macular degeneration (AMD) is an insidious process that increases in prevalence and severity predictably with age. The end stage of this condition causes profound loss of central vision. In the Beaver Dam Eye Study, in persons who were aged 75 years or older, the 15-year cumulative incidence of early stage AMD in the more severely involved eye was 24% and of late stage AMD it was 8%.¹ In that study, more than 52% of eyes with incident severe loss of vision (20/200 or poorer) had late-stage AMD.²

There are 2 forms of late-stage AMD, the neovascular or “wet” type and geographic atrophy or “dry” type. In the recent past, interventions to prevent visual loss from neovascular AMD involved laser photocoagulation of subretinal new vessels to decrease the risk of subretinal bleeding, detachment of the retinal pigment epithelium and sensory retina, retinal thickening, and subsequent scarring of the central retina. Usually, there were recurrences of the subretinal new vessels despite photocoagulation treatment. More recently, intravitreal injections of anti–vascular growth factors have been shown to reduce loss of vision in eyes with neovascular AMD, and in many cases to improve vision by up to 33.8% compared with placebo treatment.³ Although the benefits of this therapy have been shown in randomized controlled trials, these treatments are costly, may require multiple injections over a prolonged time, and do not improve vision to nonimpaired levels in the majority of eyes treated. Moreover, no treatments have been shown to be efficacious once geographic atrophy is present.

To date, the Age-Related Eye Disease Study (AREDS)⁴ has been the only completed, randomized controlled trial of antioxidant and zinc supplement therapy to prevent or retard progression of AMD. This study found about a 25% reduction of risk of progression of AMD, from moderately severe early stage AMD to late stages, either geographic atrophy or neovascular AMD. No significant effect was found on the incidence of early stage lesions of AMD or progression along a scale of earlier lesions of small drusen to more severe lesions (but not end-stage) AMD.

Until relatively recently, little was known (besides age) about factors associated with the incidence and progression of AMD. However, epidemiological studies performed over the past 20 years have shown associations of smoking,^{5 - 6} blood pressure,⁷ diet,⁸ physical activity,⁷ and inflammatory markers⁹ with AMD. The discovery of genetic factors (eg, complement factor H¹⁰ ) has provided further insights regarding risk of AMD and may in the future result in the development and application of new approaches for preventing AMD at even earlier stages.

In their article in the April issue of the Archives of Ophthalmology, Rein et al¹¹ point out that in 2004 the estimated annual cost of treatment of AMD in the United States was $575 million. Thus, even now this disease is not a trivial problem as a cause of visual disability and as an item of cost for health care. Rein and colleagues¹¹ also attempt to estimate the burden of this disease in 2050. They have amassed the disparate sources of information about AMD to estimate the relative effects of an increasing number of elderly persons, the high-risk population, and the preventive and treatment modalities currently available to forecast the burden of AMD by 2050. In addition, they consider varying effects of the potential interventions and also varying estimates by ethnicity based on the US Census. This is important because prevalences of early stage and late-stage AMD seem to differ among the larger racial and ethnic groups in the United States. The authors conclude that although the prevalence of AMD is likely to increase by 2050, some of the effects of the disease on visual loss will be ameliorated by current medical interventions.

However, recent evidence suggests that there is another time trend that would counter the potential increased number of cases over the next 40 years. Klein et al¹² found an odds ratio of 0.70 (95% confidence interval, 0.62-0.80) for 5-year incidence of early stage AMD for more recent 5-year birth cohorts (controlling for relevant confounders). Also, with the decreasing frequency of risk factor levels for AMD (decreased cigarette smoking and improved blood pressure control), there may be successive decreases in incidence of AMD in the future that might further offset the burden of this disease as the population ages. Prevention being a more desirable way to deal with the disease than treatment, this would be welcome news.

Forecasting is iffy business. It is an attempt to estimate in unknown situations. While Rein et al have marshaled much data and considerable statistical firepower, real validation always occurs in the future. Thus, while planning for the costs and the attendant ophthalmic needs for AMD that might be generated by virtue of an increased number of elderly persons in the population, it also may be reasonable to hope for a better future.