Cuticular drusen, HRF May Predict Macular Complications in Drusenoid PED

Although most macular complications occur after drusenoid PED collapse, about one third of cases develop GA or neovascularization prior to collapse, according to this study. Therefore, the authors urge clinicians to vigilantly monitor these patients to recognize high-risk features that predict complications—such as cuticular drusen and hyperreflective foci—rather than predicting the sole collapse.  These images from the study show drusen evolution into a plateau. (A) Baseline scan of a drusenoid pigment epithelial detachment (dPED) seen as a dome-shaped RPE-basal lamina elevation (inset); (B) At two years, the dPED demonstrates a significant growth with an obvious thinning of the RPE at the apex (yellow arrowhead) with RPE migration in a plume pattern (peach arrowhead); (C) At three years, the dPED collapsed, leaving a plateau signature, better seen on magnification as a residual ghost structure with a thin hyperreflective border (teal arrowheads) and a hyporeflective interior with punctate hyperreflectivities. Posterior choroidal hypertransmission can be also appreciated (star). Photo: Fragiotta S, et al. Ophthalmol Sci. October 15, 2025. Click image to enlarge. A relatively common feature in age-related macular degeneration (AMD), drusenoid retinal pigment epithelial detachment (dPED) often leads to the development of macular complications over time. A new study in Ophthalmology Science aimed to investigate the prognostic biomarkers linked to this particular AMD phenotype, with the objective of identifying indicators that can predict the onset of serious complications, including macular neovascularization (MNV) and geographic atrophy (GA). The results showed that certain imaging findings, especially the presence of cuticular drusen and hyperreflective foci, strongly predicted the development of macular complications. Furthermore, complications presented in more than 60% of patients who experienced dPED collapse.The retrospective cohort study involved a total of 71 eyes from 51 patients, with a mean age of 75.7 years, all diagnosed with dPED associated with AMD. Participants had a minimum follow-up of 24 months and were closely monitored using OCT, color fundus photography and fluorescein angiography. Over an average follow-up period of 37.5 months (range: 24 to 104 months), the research revealed a 39.4% incidence of dPED collapse, with 60.7% of these cases subsequently developing complications. A smaller yet notable percentage of patients (39.3%) developed complications before the dPED collapse occurred, which the researchers explained in their paper “makes the prediction of complications more important from a prognostic perspective than predicting the sole collapse.” MNV developed in 12 out of 71 eyes (16.9%), while a higher incidence of atrophic changes was seen in 21.1% of eyes. Two imaging features emerged as significant predictors of macular complications: the presence of cuticular drusen at baseline (hazard ratio: 3.8) and, to an even greater extent, hyperreflective foci (hazard ratio: 6.6). The analysis employed a Fine-Gray competing risks model, which is adept at accounting for the mutually exclusive nature of outcomes like MNV and GA. Those results revealed that the presence of cuticular drusen at baseline was associated with an elevated subhazard ratio of 18.1 for the development of MNV, while hyperreflective foci demonstrated a significant association with increased risk for GA, yielding a subhazard ratio of 6.69. Furthermore, disruption of the external limiting membrane at baseline was additionally linked to GA, with a subhazard ratio of 3.69. In their paper on the study, the authors explained how their findings corroborate those from the Age-Related Eye Disease Study (AREDS), which highlighted that dPED significantly heightens the risk of progression to macular atrophy and neovascularization, with a five-year progression rate of 42%, compared to 25% in eyes with large drusen and hyperpigmentation. This study found a similar complication rate of 39.4% over an average of 36.5 months. “Patients exhibiting high-risk features could benefit from closer surveillance and a tailored multimodal imaging approach, enabling earlier detection of neovascular conversion and timely initiation of anti-vascular endothelial growth factor treatment to avoid irreversible photoreceptor damage and fibrosis,” the researchers concluded. They added, “Further research should focus on better characterizing and phenotyping these structural modifications to enhance our understanding of the underlying pathogenic mechanisms.”Click here for the journal source. Fragiotta S, Querques G, Polito MS, et al. Structural biomarkers influencing drusenoid pigment epithelial detachment lifecycle and the development of late macular degeneration. Ophthalmol Sci. October 15, 2025. [Epub ahead of print].This article was developed by the editorial staff in conjunction with experts in the field. 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