Structural biomarkers influencing drusenoid pigment epithelial detachment lifecycle and the development of late macular degeneration

Purpose: Drusenoid pigment epithelial detachment (dPED) is a notable phenotype in age-related macular degeneration (AMD), often evolving into macular complications such as macular neovascularization (MNV) and geographic atrophy (GA). The aim of this study was to identify potential prognostic biomarkers associated with the development of both MNV and GA. Design: Retrospective, cohort study Subjects, Participants, and/or Controls: Patients with dPED in the setting of AMD. Methods: This observational study analyzed optical coherence tomography (OCT) biomarkers to assess the dPED lifecycle and identify features predictive of macular complications. Seventy-one eyes with dPED from 51 patients were reviewed over an average follow-up of 37.5 ± 17.6 months (range: 24–104), examining structural alterations via multimodal imaging, which include color fundus photograph (CFP), fundus autofluorescence, OCT, while fluorescein angiography and/or indocyanine green angiography (ICG) were performed as needed. Associations between baseline biomarkers and macular complications were assessed using Cox proportional hazards models with a frailty term to account for inter-eye correlation. The Fine-Gray model was used to account for competing risk analysis. Results: Key findings included a 39.4% incidence of dPED collapse, with 60.7% of cases progressing to complications post-collapse. In the multivariable Cox proportional model, cuticular drusen [Hazard ratio(HR): 3.8, 95% confidence interval [CI]: 1.62–9.2, P = 0.002] and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95%CI: 1.97-22, p=0.02) represented the main prognostic prognostic indicators of macular complications. In the Fine–Gray competing risks analysis, cuticular drusen remained a significant independent predictor (sHR = 18.1, 95% CI: 1.89–174, p = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98–22.61, p = 0.002) and external limiting membrane (ELM) disruption at baseline (sHR = 3.69, 95% CI: 1.03–13.14, p = 0.044) were factors significantly associated with increased GA risk. Conclusions: These results underscore the prognostic relevance of specific imaging biomarkers in dPED. Recognizing these features early may support timely treatment and help prevent irreversible photoreceptor and retinal pigment epithelium damage.