KCNV2-associated retinopathy is an autosomal recessive cone-rod dystrophy with abnormal photopic responses associated with ‘supernormal’ and delayed rod ERG b-waves. Patients have reductions in cone-mediated vision including photophobia, with some experiencing nyctalopia, and progression over time.
There are currently no treatments for KCNV2-associated retinopathy. However, there is a limiting lack of robust long term natural history data in large genetically proven groups of patients with the disease. These data are needed to be able to design clinical trials of future gene replacement therapy – and also to be able to provide more informed advice on prognosis and facilitate genetic counselling.
I prospectively investigated and performed in depth clinical phenotyping of the condition with cutting-edge technology, including custom-built adaptive optics scanning laser ophthalmoscopy (AOSLO) and advanced analysis of retinal sensitivity measures to topographically model visual field data from the microperimetry.
Our data suggests wide window of structural and functional preservation with an overall stable natural history. The genotype-phenotype analysis performed herein suggests a relatively milder disease course in patients with two missense variants, as opposed to loss-of-function mutations. Furthermore, we have identified the first hypomorphic allele in KCNV2, which was previously classified as benign, and we provide clinical and molecular evidence towards the reclassification of this variant.