Interocular Symmetry of Foveal Cone Topography in Congenital Achromatopsia

ABSTRACT

Purpose: To determine the interocular symmetry of foveal cone topography in achromatopsia (ACHM) using non-confocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO).

Methods: Split-detector AOSLO images of the foveal cone mosaic were acquired from both eyes of 26 subjects (mean age 24.3 years; range 8–44 years, 14 females) with genetically confirmed CNGA3- or CNGB3-associated ACHM. Cones were identified within a manually delineated rod-free zone. Peak cone density (PCD) was determined using an 80 × 80 μm sampling window within the rod-free zone. The mean and standard deviation (SD) of inter-cell distance (ICD) were calculated to derive the coefficient of variation (CV). Cone density difference maps were generated to compare cone topography between eyes.

Results: PCD (mean ± SD) was 17,530 ± 9,614 cones/mm² and 17,638 ± 9,753 cones/mm² for right and left eyes, respectively (p = .677, Wilcoxon test). The mean (± SD) for ICD was 9.05 ± 2.55 µm and 9.24 ± 2.55 µm for right and left eyes, respectively (p = .410, paired t-test). The mean (± SD) for CV of ICD was 0.16 ± 0.03 µm and 0.16 ± 0.04 µm for right and left eyes, respectively (p = .562, paired t-test). Cone density maps demonstrated that cone topography of the ACHM fovea is non-uniform with local variations in cone density between eyes.

Conclusions: These results demonstrate the interocular symmetry of the foveal cone mosaic (both density and packing) in ACHM. As cone topography can differ between eyes of a subject, PCD does not completely describe the foveal cone mosaic in ACHM. Nonetheless, these findings are of value in longitudinal monitoring of patients during treatment trials and further suggest that both eyes of a given subject may have similar therapeutic potential and non-study eye can be used as a control.

KEYWORDS:

• Achromatopsia
• interocular symmetry
• fovea
• retinal imaging
• cone photoreceptors

Acknowledgments

The authors would like to thank Alexander Salmon, Erica Woertz, and Jenna Cava for helpful discussions, Phyllis Summerfelt for facilitating subject visits, Brian Higgins for managing data, and Erin Curran for managing human subject protocols.

Presented in part at ARVO Annual Meeting 2018 in Honolulu, HI and FASEB Biology and Chemistry of Vision Conference 2019, in Steamboat Springs, CO.

Disclosure statement

Joseph Carroll has received funding support from Applied Genetic Technologies Corporation, consultant fees from MeiraGTx, and personal financial interest in Translational Imaging Innovations. Michel Michaelides has received consultant fees from MeiraGTx. Mark Pennesi and Byron Lam have received funding support from Applied Genetic Technologies Corporation. Christine Kay has received funding support and consultant fees from Applied Genetic Technologies Corporation. The authors report no other conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

Research reported in this publication was supported by the National Eye Institute of the National Institutes of Health under award numbers [R01EY017607], [P30EY001931], [P30EY010572], [R24EY022023], [T32EY014537], [T32GM080202], and [F32EY029148], and by the National Center for Advancing Translational Sciences under award number [UL1TR001436]. This investigation was conducted in part in a facility constructed with support from a Research Facilities Improvement Program, grant number [C06RR016511] from the National Center for Research Resources, NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by an grant from Research to Prevent Blindness to CEI, the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, Onassis Foundation, Leventis Foundation, The Wellcome Trust (099173/Z/12/Z), Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, Retina UK, the Foundation Fighting Blindness (USA), the Gene and Ruth Posner Foundation (Milwaukee, WI), and Applied Genetics Technology Corporation (Alachua, FL).