Abstract
Purpose :
Hyper-reflective clumps (HRCs) are microscopic structures associated with geographic atrophy (GA) in AMD that were identified with flood-illumination adaptive optics (FIAO). HRCs accumulate within and around GA, migrate at variable rates, and change in number and/or disappear over time. HRCs were hypothesized to be macrophages that accumulated melanin, which is autofluorescent (AF) in the near-infrared (NIR), through the phagocytosis of RPE debris. Here we evaluated the NIRAF of HRCs.
Methods :
Five patients with extrafoveal GA were imaged where FIAO had detected HRCs in a previous study (3-4 years ago). All underwent FIAO to determine HRC status and then AOSLO using NIR light (795Δ16) for illumination/excitation. An optical 7-fiber bundle collected confocal and multi-offset light; NIRAF (814–850 nm) was detected in a separate channel. Two patients were imaged 3 months later. Images were registered, averaged, and processed to generate confocal, AF, offset aperture, and multi-offset images; HRCs were segmented manually on FIAO images and compared across modalities.
Results :
HRCs were still present in 4/5 eyes and most (85%; n=153/181) were AF. HRCs were hypo-reflective in offset aperture AOSLO but disappeared in multi-offset images. HRC AF signal varied. Most uniformly dark HRCs on FIAO were AF in AOSLO while heterogeneous HRCs showed a smaller area or no AF, occasionally with phase contrast on multi-offset. In the patient with no visible HRCs, several phase contrast objects were seen where HRCs had previously been; nearly all of these had moved by the 3 month follow-up.
Conclusions :
Most HRCs were AF and invisible in multi-offset images. The latter suggests they are absorptive as differencing of offset aperture images should cancel the absorptive contrast and enhance the phase contrast. These findings are consistent with the hypothesis that these HRCs contain melanin. However, 15% were not AF, so more work is needed to understand their origin, composition, and evolution. Interestingly, we saw little GA progression and many high contrast phase objects, possibly immune cells, in one patient where HRCs previously had been, suggestive of an adaptive wound-healing response. Further study is needed to understand the interplay between HRCs and macrophages and their relationship to GA progression in AMD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.