Muthiah, Manickam (Nick); (2018) Adaptive Optics Imaging of Cone Photoreceptors in Retinal Diseases. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The rationale for performing observational studies in normal healthy subjects, age-similar controls and patients with diabetic macular ischaemia and patients post-macular translocation (autologous RPE transplantation) surgery was to further understand the role of Adaptive Optics Camera Flood Illumination System in photoreceptor imaging in these settings. This would inform us whether it would ultimately allow monitoring of patients with progressive photoreceptor cell loss and whether AOC could play a part in clinical trials involving cell replacement therapy and other new modalities of retinal treatment. / Study Purpose: I investigated the feasibility and ability of using an AOC to detect cone photoreceptor cell loss relative to normal subjects in patients with diabetic macular ischaemia and patients post-macular translocation (autologous RPE transplantation) surgery. / Study Design: To describe a set of exploratory observational, prospective case-control study using normal eyes as controls in eyes affected by diabetic macular ischaemia and patients post-macular translocation surgery (autologous RPE transplantation) for neovascular AMD prior to anti-VEGF era. Multimodal baseline measurements are used for estimating correlation between various measures of cone photoreceptor cell function and structure. Baseline repeated measurements are also used for estimating test - retest variability of O imaging. This will be used to power future studies. / Results: This AO imaging study in retinal health and disease has demonstrated that the normative data obtained from the rtx1 AO flood illumination camera correlates well to that from histology and AO-SLO systems. Image quality grading by automated and manual techniques is technically feasible and crucial prior to analyses of the image data from the point of disease assessment. The automated cone counts are still inaccurate and the gold standard at present remains manual count especially in images of unknown quality or from potentially diseased retina. There is a strong relationship in DMI between structure (quantitative metrics and indices of the cone photoreceptors measured by AO) and function, retinal sensitivity. AO has detected early changes in PR structure not delineated by OCT in DMI. Longitudinal serial assessments of cone changes were successful and revealed the “regeneration” of cone outer segment (OS), a new finding in ischaemic diabetic maculopathy. / Conclusion: The combination of 3 metrics and the novel indices generated from analyses of AO imaging datasets described in this thesis has the potential translational value in DMI, and for other retinal diseases, once these imaging biomarkers are studied in a larger sample size. The biomarkers could be invaluable for retinal diseases to be monitored longitudinally. AO in vivo imaging could enable targeted and effective cellular/ molecular retinal therapy in future.

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