Visual function in aging and age-related macular degeneration including subretinal drusenoid deposits

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the developed world among people over 50 years of age. Although AMD is clinically characterised by the presence of drusen, subretinal drusenoid deposits (SDD) have also been recognized as a distinct morphological feature that confers increased risk of developing advanced AMD. To date, there has been a lack of validated biomarkers that can capture early changes in visual function that strongly correlate to the anatomical alterations which also include SDD phenotype. This thesis aimed to explore functional and structural markers to differentiate between healthy eyes (n=11) and intermediate AMD (iAMD) with SDD (n=11) and without SDD (n=17) and non-foveal atrophic AMD (n=11). Firstly, I assessed scotopic thresholds using a novel dark-adapted chromatic (DAC) perimeter, in healthy aging and in varying AMD disease. Individuals with SDD had depressed retinal sensitivity centrally, particularly inferiorly and nasally. Functionally, eyes with SDD were comparable to eyes with non-foveal atrophy, but structurally differed in outer nuclear layer (ONL) and total retinal volumes and thicknesses. Importantly, only rod-mediated tests were able to distinguish iAMD with and without SDD. Another aim of this thesis was to explore the efficacy of 670nm light on aging and AMD. Although an improvement in scotopic thresholds was observed in healthy aged eyes (n=4) compared to younger eyes (n=5), a pilot study conducted in 40 participants over the age 55 years (12 control, 28 with intermediate AMD) refuted any clinical benefit. In conclusion, this thesis supports the need to re-classify the AMD severity scale by incorporating eyes with SDD as a separate group. This phenotype should be sub-analysed in clinical trials evaluating potential prophylactic agents to delay the progression. Scotopic sensitivity offers diagnostic value, but rod intercept time offers both prognostic and diagnostic value as candidate biomarkers