John R. Grigg

Background KCNV2 ‐associated retinopathy is an autosomal recessive inherited retinal disease classically named cone dystrophy with supernormal rod response (CDSRR). This study aims to identify the best biomarker for evaluating the condition. Methods A retrospective review of eight patients from seven families with genetically confirmed KCNV2 ‐associated retinopathy was performed. The best corrected visual acuity (BCVA), full‐field electroretinogram (ffERG), pattern ERG (pERG), fundus imaging: retinal photograph and fundus autofluorescence (FAF), and optical coherence tomography (OCT) were analysed. Results There was a disproportionate increase in b‐wave amplitude with a relatively small light intensity increase, especially between the two dimmest stimuli of DA 0.002 and 0.01 (−2.7 and −2.0 log cd.s/m 2 ). The a‐wave amplitude was normal. The a‐wave peak time was delayed in all stimuli. The b‐wave peak time was delayed compared to normal, but the gap tightened as intensity increased. The b:a wave ratio was above or at the upper limit for the reference values. FAF bull's eye maculopathy pattern was prominent and variable foveal disruption on OCT was apparent in all patients. Legal blindness was reached before the age of 25. Conclusions We identified three potential electrophysiology biomarkers to assist in evaluating future therapies: the disproportionate b‐wave amplitude jump, delayed a‐wave and b‐wave peak time, and the higher than normal b:a wave ratio. Any of these biomarkers found with photoreceptor ellipsoid zone foveal‐perifoveal disruption should prompt consideration for KCNV2 retinopathy. The BCVA natural history data suggests the probable optimum therapeutic window in the first three decades of life.