Reticular Pseudodrusen Subtypes and Their Interaction With Soft Drusen: Longitudinal Structure-Function Analysis

To evaluate longitudinal structure-function relationships of reticular pseudodrusen (RPD) subtypes and their interaction with soft drusen (SD) on retinal sensitivity (RS) in intermediate age-related macular degeneration (AMD).

Retrospective cohort study.

Forty-six eyes of 28 patients diagnosed with intermediate AMD or RPD who underwent microperimetry at two time points 6 to 12 months apart.

RPD presence and subtype (dot or ribbon) and SD were assessed individually at each of 37 Early Treatment Diabetic Retinopathy Study grid test points on co-registered multimodal imaging. Linear mixed-effects models estimated baseline RS and its change by drusen composition, with test-point location as a fixed effect and adjustment for clinical covariates, plus baseline RS for the change analysis.

Change in RS over follow-up and baseline RS, according to drusen composition.

At baseline, ribbon-type RPD regions showed lower RS than lesion-free regions (mean difference 0.72 ± 0.24 dB, P = .002), whereas dot-type RPD did not differ (P = .120); SD was independently associated with reduced RS (P = .021). No baseline RPD subtype × SD interaction was observed. Longitudinally, a significant interaction was found (P = .005): regions with both ribbon-type RPD and SD showed the greatest RS decline, whereas RPD subtypes did not differ without SD (all P > .9).

The functional impact of RPD varies by subtype and coexistence with SD. Ribbon-type RPD is associated with greater RS impairment, particularly when combined with SD, highlighting the importance of lesion phenotype in functional risk assessment.