Ophthalmology (Eye & Ear Hospital) - Theses
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ItemPredicting progression in age-related macular degeneration( 2023-08)Background: Predicting which individuals will develop vision-threatening complications of age-related macular degeneration (AMD) is a challenging task, as traditional models based on colour fundus photography (CFP) correctly identify less than half of those who subsequently develop late AMD at 95% specificity. Thus, there is a great need to improve risk stratification for individuals with the early stages of AMD. Aims: To examine the prognostic significance of novel pathological characteristics related to drusen phenotypes and pigmentary abnormalities in the early stages of AMD. Methods: Retinal imaging data from 280 eyes from 140 individuals with bilateral large drusen enrolled in a longitudinal observational study was evaluated. Individuals underwent multimodal imaging (MMI) and microperimetry at baseline and then 6-monthly for up to 3-years. Disease progression was primarily evaluated based on the development of MMI-defined late AMD, and secondarily based on the rate of visual sensitivity decline on microperimetry prior to late AMD development. Four retinal specialists assessed the likelihood that each eye at baseline would progress with CFP, and then with MMI, to determine if MMI improves their ability to predict late AMD development. Baseline images were assessed for the: (i) presence of cuticular drusen, and extent of (ii) hyporeflective cores within drusen (HCD), (iii) hyperpigmentary abnormalities (HPAs), and (iv) hyperreflective foci (HRF) that do not spatially correspond to HPAs [HRF(OCT+/CFP-)]. The association with progression and impact on visual sensitivity of each feature was examined, including adjustments for well-established risk factors for progression (drusen volume from optical coherence tomography, presence of pigmentary abnormalities on CFP, and age). Results: The prediction of late AMD development by retinal specialists was improved when using MMI compared to CFP. However, a basic prediction model (age, presence of pigmentary abnormalities, and drusen volume) outperformed clinicians. In this cohort, neither the presence of cuticular drusen nor extent of HCD were significantly associated with an increased rate of progression to late AMD, reduced mean visual sensitivity at baseline, or an increased rate of visual sensitivity decline, after adjusting for well-established risk factors of progression. The quantification of HPA extent did not significantly improve the prediction of late AMD development compared to HPA presence, and the addition of HRF(OCT+/CFP-) extent to HPA extent also did not improve performance. Both HPA and HRF(OCT+/CFP-) extent were independently associated with reduced sector-based visual sensitivity, with the latter also associated with a significantly faster rate of visual sensitivity decline. Conclusions: Accounting for drusen phenotypes such as cuticular drusen and HCD, or the quantity of HPAs and HRF(OCT+/CFP-), did not significantly improve the prediction of late AMD development above what could be achieved by well-established risk factors. However, a basic prediction model using these parameters – drusen volume, presence of pigmentary abnormalities and age – outperformed retinal specialists, suggesting that such a model could improve counselling and monitoring of individuals in clinical practice. Such a model could also be used to better identify an enriched cohort to improve feasibility of future interventional trials, and thus help expedite the discovery of preventative treatments in the early stages of AMD.