Age-related maculopathy (ARM) is the leading cause of irreversible vision impairment in older adults in the industrialized world. ARM is a complex, multi-factorial disease in which central retinal photoreceptors are lost, either by an atrophic process, the most common disease express, or by a neovascular event, the most destructive form causing severe vision impairment. Of the 14 million Americans with ARM, the vast majority of these individuals, 12 million, have early disease. At present, physicians have nothing to offer them in terms of proven treatments to arrest the progression of early ARM, nor do they have proven strategies for preventing the disease altogether. Fortunately, recent discoveries have stimulated research toward developing preventative therapies and strategies that arrest early disease progression. An increasing body of evidence suggests that inflammation and lipids (cholesterol) play important roles in pathogenesis. Scientists are already working to translate basic research discoveries in these areas to experimental therapies for ARM prevention, whose efficacy must be demonstrated in clinical trials. The primary outcome measures used in clinical trials on advanced ARM visual acuity and grading of stereo fundus photos are not well suited as primary endpoints in clinical trials on early ARM because they are insensitive to disease progression in the early phases of ARM. Previous research indicates that rod-mediated dark adaptation may be an alternative outcome for consideration, for several reasons. First, rod photoreceptors are vulnerable to degeneration and dysfunction in the earliest phases of ARM. Second, kinetic measures of scotopic function (i.e., those that reflect the recovery of sensitivity over time) are more sensitive than static measures in detecting early ARM. Third, rod- mediated dark adaptation taps into the retinoid cycle, which is likely disrupted in ARM by lesions in the RPE/Bruch's membrane complex which disrupt nutritional transport to rod photoreceptors. A critical question that remains unaddressed is whether rod-mediated dark adaptation impairment precedes the development of early ARM as defined by the gold standard of fundus appearance. This is an important question because if rod- mediated dark adaptation delays precede the clinical signs of the disease, this functional assay would have potential as a diagnostic marker for the disease and/or as an outcome measure in clinical trials and epidemiological studies of early ARM. A prospective study is proposed to address this and related questions.
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