A prospective longitudinal study of retinal structure and function in achromatopsia.

PubMed ID: 25103266

Author(s): Aboshiha J, Dubis AM, Cowing J, Fahy RT, Sundaram V, Bainbridge JW, Ali RR, Dubra A, Nardini M, Webster AR, Moore AT, Rubin G, Carroll J, Michaelides M. A prospective longitudinal study of retinal structure and function in achromatopsia. Invest Ophthalmol Vis Sci. 2014 Aug 7;55(9):5733-43. doi: 10.1167/iovs.14-14937. PMID 25103266

Journal: Investigative Ophthalmology & Visual Science, Volume 55, Issue 9, Aug 2014

PURPOSE To longitudinally characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical gene therapy trials.

METHODS Thirty-eight molecularly confirmed ACHM subjects underwent serial assessments, including spectral domain optical coherence tomography (SD-OCT), microperimetry, and fundus autofluorescence (FAF). Foveal structure on SD-OCT was graded and compared for evidence of progression, along with serial measurements of foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness. Fundus autofluorescence patterns were characterized and compared over time.

RESULTS Mean follow-up was 19.5 months (age range at baseline, 6-52 years). Only 2 (5%) of 37 subjects demonstrated change in serial foveal SD-OCT scans. There was no statistically significant change over time in FTRT (P = 0.83), ONL thickness (P = 0.27), hyporeflective zone diameter (P = 0.42), visual acuity (P = 0.89), contrast sensitivity (P = 0.22), mean retinal sensitivity (P = 0.84), and fixation stability (P = 0.58). Three distinct FAF patterns were observed (n = 30): central increased FAF (n = 4), normal FAF (n = 11), and well-demarcated reduced FAF (n = 15); with the latter group displaying a slow increase in the area of reduced FAF of 0.03 mm(2) over 19.3 months (P = 0.002).

CONCLUSIONS Previously published cross-sectional studies have described conflicting findings with respect to the age-dependency of progression. This study, which constitutes the largest and longest prospective longitudinal study of ACHM to date, suggests that although ACHM may be progressive, any such progression is slow and subtle in most patients, and does not correlate with age or genotype. We also describe the first serial assessment of FAF, which is highly variable between individuals, even of similar age and genotype.