Sub retinal pigment epithelium hyporeflective spaces preceding large drusen collapse.

Purpose: To describe and study hyporeflective sub retinal pigment epithelium (RPE) spaces in large drusen and drusenoid pigment epithelial detachment prior to collapse.

Method: Retrospective longitudinal study which enrolled patients with large and very large drusen due to intermediate age-related macular degeneration (AMD). The following optical coherence tomography (OCT) parameters were assessed: Drusen size (maximum width and height), OCT biomarkers of RPE atrophy, presence of intraretinal and subretinal fluid (IRF, SRF), acquired vitelliform lesion and sub RPE regions of hyporeflectivity within the PED compartment.

Results: Of the 50 eyes from 41 patients (mean age of 77.1 ± 9 years, 78% women) with large and very large drusen, 16 eyes progressed to collapse. Eyes with sub RPE hyporeflective spaces (n=8 eyes, 50%) were associated with greater drusen width and height than eyes without sub RPE hyporeflective spaces. At the collapse visit, eyes with sub RPE hyporeflective spaces displayed poorer visual acuity and greater iRORA (incomplete RPE outer retinal atrophy) and cRORA (complete RORA) length than eyes without sub RPE hyporeflective spaces (p=0.004 and p=0.04, respectively).

Conclusion: Sub RPE hyporeflective spaces are a novel OCT finding of large and very large drusen that collapse to atrophy. Progressive RPE dysfunction and failure may lead to reduced drusenoid material formation and progressive degenerative hydration of the large drusen prior to collapse, but this awaits confirmation with histopathological analysis.