Genotype-dependent variability in residual cone structure in achromatopsia: toward developing metrics for assessing cone health.

Alfredo Dubra // Publications // Oct 02 2014

PubMed ID: 25277229

Author(s): Dubis AM, Cooper RF, Aboshiha J, Langlo CS, Sundaram V, Liu B, Collison F, Fishman GA, Moore AT, Webster AR, Dubra A, Carroll J, Michaelides M. Genotype-dependent variability in residual cone structure in achromatopsia: toward developing metrics for assessing cone health. Invest Ophthalmol Vis Sci. 2014 Oct 2;55(11):7303-11. doi: 10.1167/iovs.14-14225. PMID 25277229

Journal: Investigative Ophthalmology & Visual Science, Volume 55, Issue 11, Oct 2014

PURPOSE Gene therapy trials for inherited photoreceptor disorders are planned. Anatomical metrics to select the best candidates and outcomes are needed. Adaptive optics (AO) imaging enables visualization of photoreceptor structure, although analytical tools are lacking. Here we present criteria to assess residual photoreceptor integrity in achromatopsia (ACHM).

METHODS Two AOSLOs, at the Medical College of Wisconsin and Moorfields Eye Hospital, were used to image the photoreceptor mosaic of 11 subjects with ACHM and 7 age-matched controls. Images were obtained, processed, and montaged using previously described methods. Cone density and reflectivity were quantified to assess residual cone photoreceptor structure.

RESULTS All subjects with ACHM had reduced numbers of cone photoreceptors, albeit to a variable degree. In addition, the relative cone reflectivity varied greatly. Interestingly, subjects with GNAT2-associated ACHM had the greatest number of residual cones and the reflectivity of those cones was significantly greater than that of the cones in the subjects with CNGA3/CNGB3-associated ACHM.

CONCLUSIONS We present cone reflectivity as a metric that can be used to characterize cone structure in ACHM. This method may be applicable to subjects with other cone disorders. In ACHM, we hypothesize that cone numerosity (and/or density) combined with cone reflectivity could be used to gauge the therapeutic potential. As gene replacement would not be expected to add cones, reflectivity could be a more powerful AO-metric for monitoring the cellular response to treatment and could provide a more immediate indicator of efficacy than behavioral measures, which may take longer to change.

Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.