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.