Mechanisms of Dark Adaptation and their link with early Age Related Macular Degeneration

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Abstract

Age-related macular degeneration (AMD) is the major cause of blindness in older people in developed countries. Although the early stages of the disease are thought to be symptomless, it is known that rod function systematically deteriorates as the disease progresses. The rod-mediated sensitivity recovery, called dark adaptation (DA), is abnormal in early AMD and it is clear this alteration precedes changes in visual function such as visual acuity (VA). In fact by the time VA is abnormal in AMD, many millions of rods will have been lost. DA has not been extensively studied in clinics due to the prolonged testing time. The work described has four principal aims. First to investigate the homogeneity of the rod dysfunction in normal aging; second to study DA changes at different locations across the retina in early AMD; third to compare morphological features of early AMD fundus images with scotopic and photopic function; and fourth to assess new strategies for reducing the duration of the DA procedure. Testing DA at different locations (3° and 5.5° eccentricity) in young and older eyes indicated that the age-related deficit is likely to be uniform across the retina. Using the same method in early stage AMD patients, revealed wide variations in the pattern of DA abnormalities. A MANOVA showed a strong location effect (p<0.001). The extra information provided by the presence of a second stimulus, increased the diagnostic ability of the test. The extra stimulus did not place additional demands on observers. Chapter 5 investigates the link between structural and functional abnormalities in early AMD eyes. The strongest association between the two was found for the rod-mediated parameters of DA. S2, the second rod phase of DA, predicted both the colour fundus and the fundus autofluorescence classification closely (rho=0.60, p<0.0001). S2 slows as the severity of the fundus changes increases suggesting that S2 is an accurate index of the severity of the disease. Chapter 6 presents preliminary results of new strategies aimed at improving the DA technique. For example, the introduction of a red background reduces the time to reach the rod-cone break but does not affect S2. The overall aim of the work was to understand the functional deficit in AMD at its earliest stages. This is crucial for the successful development and testing of new therapies and management strategies.

Keyword(s)

Age related Macular Degeneration ; Dark Adaptation ; Rod function

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