Gango Omer, AA; (2013) Heterogeneity of Sub-retinal Deposits in MacTel Type 2 and Ageing. Doctoral thesis (PhD), UCL (University College London).

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Abstract

MacTel type 2 is a slowly progressive neurodegenerative condition primarily affecting the tem- poral area of the central retina. Subtle generalised increases in foveal autofluorescence are early sign of the disease. During the course of examining autofluorescence imaging at the Reading Centre of Moorfields Eye Hospital, we identified a new hitherto undescribed pattern of autofluorescence in patients with MacTel type 2. This pattern consists of focal hyperauto- fluorescent deposits (HADs). Cross-sectionally, we studied HADs prevalence and patterns of distribution in MacTel type 2 patients, family members and controls in fundus autofluorescence and fundus colour images. We carried out a detailed phenomenological description of HADs using a multimodal approach consisting of point-to-point correlative analysis of fundus auto- fluorescence, colour fundus imaging, fluorescein angiography imaging and high-definition OCT. Longitudinally, we examined HADs progression over a 5-year-period and HADs in the clinical progression of MacTel type 2. In parallel, we carried out in vivo investigations to examine our hypothesis that hyperautofluorescent deposits have an autofluorescent signature distinct from that of Bruch’s membrane and the RPE and that this autofluorescent signature could mark specific pathological states. We used the microprobe synchrotron X-ray fluorescence and X-ray diffraction analysis to examine the effect of trace metals and elements on drusen autofluorescence. We demonstrated that HADs are a newly identified pattern of autofluores- cence change in patients with MacTel type 2 by showing that HADs prevalence, topographical distribution, progression; all strongly correlate with the disease. We explored the potential of autofluorescence imaging as technique to derive specific information on deposits/drusen and RPE layer in pathological states. We discovered the presence of calcium is associated with the precipitation of hydroxyapatite, a constituent of drusen that had not been described before. Future studies are required to confirm the potential for the use of HADs as a biomarker the in clinical settings.

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