Fundus Refraction Offset as a Personalized Biomarker for 12-Year Risk of Retinal Detachment

PURPOSE. The purpose of this study was to investigate the potential of a novel anatomical metric of ametropia-fundus refraction offset (FRO)-in stratifying the risk of retinal detachment (RD) or breaks, beyond the influence of risk factors including spherical equivalent refraction (SER). METHODS. Participants from the UK Biobank with no prior history of RD/breaks were analyzed (n = 9320). The onset of RD/breaks over a 12-year follow-up period was determined based on linked healthcare data. A previously trained deep learning model was applied to each fundus photograph to predict SER. FRO was defined as the error in the fundus-predicted SER, with a negative value indicating a relatively myopic-looking fundus. Cox regression was used to examine the association of baseline FRO with RD/breaks-adjusting for baseline SER, baseline age, sex, and cataract surgery during follow-up. In a subgroup of participants (n = 7127) with high-quality optical coherence tomography scans, we additionally adjusted for baseline macular thickness (MT). All analyses initially considered any RD/breaks as the event, followed by rhegmatogenous RD/breaks. RESULTS. The mean (SD) baseline age was 54.8 (8.2) years. Sixty-four participants developed RD/breaks (of any subcategory), with a mean (SD) of 7.0 (3.3) years between baseline and disease onset. A more negative baseline FRO was independently associated with an increased risk of any RD/breaks (adjusted hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.50-0.87, P = 0.003) and rhegmatogenous RD/breaks (HR = 0.61, 95% CI = 0.45-0.82, P = 0.001). Similar independent associations were evident in the subgroup analysis that additionally adjusted for MT. CONCLUSIONS. A more negative baseline FRO is associated with a higher risk of developing RD/breaks, even among individuals with similar baseline SER and other risk factors. This demonstrates a potential benefit of shifting towards an anatomic definition of myopia.