Using adaptive optics to assess hyporeflective clump speed and size in age-related macular degeneration in the PINNACLE Study. (PINNACLE Study Report 6).

Background/objectives: Hyporeflective clumps (HRC) are a common finding in adaptive optics ophthalmoscopy (AOO) of age-related macular degeneration (AMD). They appear on optical coherence tomography (OCT) as hyperreflective foci (HRF) or abutting the retinal pigment epithelium (RPE) layer as RPE thickening. The cellular origin of HRF is debated between migrated RPE cells and mononuclear phagocytes (MP). Microglial cells are MP known to migrate at 0.02 µm/s, but RPE migration speed is unknown. Phenotyping HRCs by migration speed and size may improve our understanding of HRFs.

Methods: Patients with non-neovascular AMD were imaged with the RTX1 retinal camera (Imagine Eyes, Orsey, France). Pairs of AOO images taken 1-3 h apart were centred on areas with multiple HRCs and compared to identify mobile HRCs. Macular OCT scans were performed immediately after initial AOO.

Results: A total of 21 pairs of images from 14 eyes of 12 patients were of adequate quality to assess HRCs. There were 411 measurable HRCs, with a mean diameter of 15.9 ± 6.0 µm. The HRCs were larger in images of atrophy (p < 0.001). Within the timeframe assessed, most HRCs remained static, but mobile HRCs were not uncommon and migrated up to 0.015 µm/s. HRFs on OCT corresponding to mobile HRCs on AOO appeared adjacent to the RPE or in the interdigitation zone.

Conclusion: AOO can detect HRC movement in AMD in images captured a mean of 105.5 min apart. HRC size and movement speed are consistent with microglial cells, but may also represent RPE cells. HRCs appear larger in images of atrophy.