Age-related macular degeneration

Summary

Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration.

Introduction

Age-related macular degeneration is the most common cause of visual impairment in individuals over the age of 55 years in developed countries.¹ The disease, in its early stages, develops slowly and asymptomatically over a number of years. Although the definition of age-related macular degeneration differs in various studies, the condition is generally characterised by extensive drusen, often associated with pigmentary abnormalities. Drusen are visualised as whitish yellow deposits under the retinal pigment epithelium and neurosensory retina. In elderly individuals, a restricted number of small drusen (<63 μm in diameter) are common; such patients are not deemed to have age-related macular degeneration because they are at low risk of developing vision loss.² Although drusen are the common denominator for age-related macular degeneration, the disease has been subdivided into three categories on the basis of the risk of developing vision loss (panel, Figure 1, Figure 2, Figure 3).

Two classification schemes have been developed to estimate the risk of progression from the early stages of age-related macular degeneration to the advanced stage. The first is a detailed scheme that generally needs careful photographic review for implementation.⁷ The second is a simplified scale that is easy to use clinically.⁸ In both schemes the risk of developing the advanced forms of age-related macular degeneration is directly associated with the extent of the drusen and the amount of hypopigmentary or hyperpigmentary changes of the retinal pigment epithelial layer. For example, based on the simplified scale, individuals with both large drusen and the pigmentary changes in both eyes, or with these lesions in one eye and advanced age-related macular degeneration in the other, have about a 50% risk of developing advanced age-related macular degeneration in 5 years.⁸ The pathogenesis of age-related macular degeneration is not well known, although a number of theories have been put forward, including oxidative stress, mitochondrial dysfunction, and inflammatory processes.9, 10, 11, 12, 13