Purpose: To characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinicaludtrials of gene therapy.udDesign: Cross-sectional study.udParticipants: Forty subjects with ACHM.udMethods: All subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry,udand molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuousudinner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), andud(5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thicknessudwas measured and presence of hypoplasia determined.udMain Outcome Measures: Photoreceptor appearance on SD-OCT imaging, foveal and ONL thickness,udpresence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters withudage and genotype.udResults: Forty subjects with a mean age of 24.9 years (range, 6e52 years) were included. Disease-causingudvariants were found in CNGA3 (n [ 18), CNGB3 (n ¼ 15), GNAT2 (n ¼ 4), and PDE6C (n ¼ 1). No variants wereudfound in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption,ud20% had an absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences inudage (P ¼ 0.77), mean retinal sensitivity (P ¼ 0.21), or fixation stability (P ¼ 0.34) across the 5 SD-OCT categories wereudevident. No correlation was found between age and foveal thickness (P ¼ 0.84) or between age and foveal ONLudthickness (P ¼ 0.12).udConclusions: The lack of a clear association of disruption of retinal structure or function in ACHM with ageudsuggests that the window of opportunity for intervention by gene therapy is wider in some individuals thanudpreviously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specificudmeasurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptorudpreservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selectingudsubjects for future trials and measuring the trials’ impact.
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