Hyperreflective Foci Along the Retinal Pigment Epithelium Predict the Onset of Large Choroidal Hypertransmission Defects in Age-Related Macular Degeneration

Purpose

In eyes with intermediate age-related macular degeneration (iAMD), we separately quantified the hyperreflective foci (HRF) along the retinal pigment epithelium (rpeHRF) and the intraretinal HRF (iHRF) to determine if the location of the HRF predicted the progression from iAMD to the onset of large persistent choroidal hypertransmission defects (hyperTDs).

Design

Post hoc subgroup cohort analysis of a prospective study.

Methods

A retrospective analysis was performed on a prospective natural history database of eyes with AMD imaged using swept-source optical coherence tomography (SS-OCT). En face images derived from choroidal slabs positioned 64 to 400 µm beneath Bruch membrane were used with a semiautomated algorithm to identify and quantify hypotransmission defects (hypoTDs) attributable to either iHRF or rpeHRF within a 5-mm fovea-centered circle. iHRF were identified on corresponding B-scans as hyperreflective lesions within the neurosensory retina, and rpeHRF were identified as areas of retinal pigment epithelium thickening. Multivariable survival analysis was performed to determine if the area measurements of either iHRF or rpeHRF were more likely to predict the onset of the first large persistent hyperTD.

Results

Of the 171 eyes with iAMD included in this study, 82 (48%) developed at least 1 large hyperTD during a median follow-up of 59.1 months. Univariable Cox regression analyses showed that rpeHRF area (P < .001), iHRF area (P = .003), and drusen volume (P < .001) were all significantly associated with the onset of the first large persistent hyperTD. However, a multivariable Cox regression model showed that only the rpeHRF area remained a significant predictor of disease progression (P < .001).

Conclusions

In iAMD eyes, the area of rpeHRF was more predictive of disease progression than either the drusen volume or iHRF, which suggests that these rpeHRF serve as harbingers of focal atrophy formation and may predict where hyperTDs form.