Absorption of light by photoreceptors initiates vision, but also leads to accumulation of toxic photo-oxidative compounds in the photoreceptor outer segment (OS). To prevent this buildup, small packets of OS discs are periodically pruned from the distal end of the OS, a process called disc shedding. Unfortunately dysfunction in any part of the shedding event can lead to photoreceptor and RPE dystrophy, and has been implicated in numerous retinal diseases, including age related macular degeneration and retinitis pigmentosa. While much is known about the complex molecular and signaling pathways that underpin shedding, all of these advancements have occurred in animal models using postmortem eyes. How these translate to the living retina and to humans remain major obstacles. To that end, we have recently discovered the optical signature of cone OS disc shedding in the living human retina, measured noninvasively using optical coherence tomography equipped with adaptive optics in conjunction with post processing methods to track and monitor individual cones in 4D. In this study, we improve on this method in several key areas: increasing image acquisition up to MHz A-scan rates, improving reliability to detect disc shedding events, establishing system precision, and developing cone tracking for use across the entire awake cycle. Thousands of cones were successfully imaged and tracked over the 17 hour period in two healthy subjects. Shedding events were detected in 79.5% and 77.4% of the tracked cones. Similar to previous animal studies, shedding prevalence exhibited a diurnal rhythm. But we were surprised to find that for these two subjects shedding occurred across the entire day with broad, elevated frequency in the morning and decreasing frequency as the day progressed. Consistent with this, traces of the average cone OS length revealed shedding dominated in the morning and afternoon and renewal in the evening.

Date Published: 28 February 2017
PDF: 8 pages
Proc. SPIE 10045, Ophthalmic Technologies XXVII, 1004517 (28 February 2017); doi: 10.1117/12.2256146

Published in SPIE Proceedings Vol. 10045:
Ophthalmic Technologies XXVII
Fabrice Manns; Per G. Söderberg; Arthur Ho, Editor(s)