Spontaneous Soft Drusen Regression without Atrophy and the Drusen Ooze

Abstract

Objective

To determine the incidence of spontaneous soft drusen (SD) regression without atrophy (DRwoA) in patients with intermediate or atrophic age-related macular degeneration (AMD), evaluate associated events, and offer potential explanations.

Design

A retrospective review of the imaging of a consecutive series of 640 eyes from 320 patients with AMD who had ≥2 years of follow-up.

Subjects

Four hundred twenty-seven eyes from 262 patients with intermediate AMD or atrophic AMD and no present or past exudative AMD.

Methods

Retinal imaging included infrared reflectance imaging, fundus autofluorescence, spectral-domain OCT, and color fundus photography.

Main Outcome Measures

The outcomes included drusen regression without atrophy with integrity of the retinal pigment epithelium (RPE) and repositioning over Bruch’s membrane. In addition, drusen that would collapse with atrophy (DCwA) in the same area simultaneously were named “sentinel” DCwA. The outcomes also included the reversibility of features of incomplete RPE, outer retinal atrophy (iRORA), and the areas (“halos”) of DRwoA around the “sentinel” drusen.

Results

Among the 427 eyes, 53 events of DRwoA were found, representing 24.17% of the eyes with SD. In 50 cases (94.33%), a “sentinel” DCwA in the vicinity was found. In 58% of the cases, a well-identifiable halo of drusen disappearance around the “sentinel” DCwA was well visible.

Conclusions

Drusen regression without atrophy is a frequently observed phenomenon linked to SD and almost invariably occurs near a “sentinel” DCwA. The coalescence of the drusen and the spatial and temporal association of the DRwoA and the DCwA strongly suggest that the drusen material of DRwoA escapes to a contiguous “sentinel” DCwA. Although the hypothesis of the disappearance of drusen material due to RPE death may explain the DCwA, it fails to account for DRwoA. Instead, the “drusen ooze” hypothesis, which posits the movement of drusen content to the subretinal space through RPE defects, may explain both the DCwA and the DRwoA. This hypothesis offers insights into the reversibility of iRORA features and suggests that therapies targeting drusen material removal before RPE disruptions could potentially prevent atrophy secondary to SD collapse.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.