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Angelos Kalitzeos, Neruban Kumaran, Michalis Georgiou, Navjit Singh, Thomas Kane, Melissa Kasilian, Alfredo Dubra, Joseph Carroll, Michel Michaelides; Natural history of foveal cone structure in RPE65-associated Leber congenital amaurosis (LCA). Invest. Ophthalmol. Vis. Sci. 2019;60(9):4584.
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RPE65-associated LCA (RPE65-LCA) is a rare, severe early-onset retinal dystrophy characterized by progressive rod then cone photoreceptor loss. We performed a prospective, observational natural history study (NCT02714816) using reflectance adaptive optics scanning light ophthalmoscopy (AOSLO) to longitudinally assess foveal cone structure in RPE65-LCA.
Image sequences of the foveal cone mosaic were acquired using a custom AOSLO. Cone outer segment (confocal AOSLO) and inner segment mosaics (split-detection AOSLO) were recorded in spatial and temporal registration. Montages of the foveal photoreceptor mosaic were created for baseline and follow-up visits.
The fovea of one eye of three molecularly confirmed RPE65-LCA female adults (mean±SD; 20±1 years old and 22.1±1.1 mm axial length, at baseline) was imaged on two visits. Two subjects had a follow-up duration of 29 months, and the third subject had 21 months. The vast majority of foveal cone outer segments did not waveguide light in confocal imaging, with the remaining few showing either multimodal reflectivity profiles or bright reflecting cones. Baseline cone inner segment mosaics were too dense to reliably resolve every single foveal cone for quantification purposes. While there were no visible changes across time in confocal AOSLO, non-confocal split-detection showed relative enlargement of inner segments for all three patients over time - indirectly revealing the reduction of foveal peak cone density with time.
The remnant foveal cone mosaic was successfully followed up over a 21 to 29 month period in three RPE65-LCA subjects to gain a deeper insight into disease progression on a cellular scale. Foveal cone photoreceptor degeneration in RPE65-LCA was indicated by a reduction in cone density and inner segment enlargement over time. Future work includes longitudinal perifoveal cone tracking, longer follow-up time in a larger cohort and comparison to Optical Coherence Tomography and visual function.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Confocal (in logarithmic display to facilitate cone visualization) and non-confocal split detection of the foveal photoreceptor mosaic in three RPE65-LCA subjects showing en face cone outer and inner segments, respectively. All crops are 300 microns wide (square).
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