Using adaptive optics to assess hyporeflective clumps as a biomarker for progression to cRORA in the PINNACLE study

Abstract

Purpose : Adaptive optics ophthalmoscopy (AOO) provides high-resolution retinal imaging that allows visualization of hyporeflective clumps (HRC). HRCs are a highly dynamic finding in age-related macular degeneration (AMD) and are thought to correspond with melanin containing cells such as hyperreflective foci or retinal pigment epithelial (RPE) thickening on optical coherence tomography (OCT). Objective assessment of HRCs may confirm their role as a biomarker of disease progression in AMD and give mechanistic insights.

Methods : Eyes with intermediate AMD were divided into those that progressed to complete RPE and outer retinal atrophy (cRORA) on OCT, and those that had stable intermediate AMD for at least 12 months. All patients received imaging of the central 12° horizontally by 4° vertically with the rtx1 camera. Baseline AOO images were used in the “stable” group, and the latest images prior to cRORA detection were included in the “pre-cRORA” group. Montaged AOO images were processed with the Phansalkar method in ImageJ to objectively assess HRCs.

Results : Images were of adequate quality to assess HRCs in 48 eyes from 38 patients. Stable eyes (n=34) showed increased mean counts (p<0.005) and increased total (p<0.007) and percentage areas (p<0.005) of HRCs compared to pre-cRORA eyes (n=14) (fig 1). Mean HRC size appeared larger in pre-cRORA patients (143µm²) than stable patients (127µm²) but this did not reach statistical significance (p=0.13). In eyes with drusenoid pigment epithelial detachments, HRCs showed lower counts, (p=0.003), area (p=0.035) and percentage area (p=0.044) than eyes with large drusen (fig 2).

Conclusions : Eyes in the 12 months prior to cRORA development show significantly fewer HRCs, and the HRCs cover a smaller area compared to eyes with stable intermediate AMD. These differences likely reflect increased HRC clustering in pre-cRORA eyes, and HRC distribution may prove a valuable biomarker in AMD.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Box whisker plots comparing HRC counts (a), total area (b), mean HRC size (c) and % area of image (d) between the pre-cRORA and stable groups.

 

Fig 2: Box whisker plots showing HRC counts (a), total area (b), mean HRC size (c) and % area of image (d) grouped by drusen subtype.