KCNV2 -associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.

Background/aims: To investigate genotype-phenotype associations in patients with KCNV2 retinopathy.
Methods: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared.
Results: Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants.
Conclusions: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.
Competing Interests: Competing interests: MG and MM consult for MeiraGTx. KF consults for Astellas Pharma, Kubota Pharmaceutical Holdings, Acucela, Novartis AG and Janssen Pharmaceuticals. Ester Carreño consults for Active Biotech and Alimera. EZ consults for Acucela, IVERIC bi, Janssen Pharmaceuticals, ProQR Therapeutics N.V., Gyroscope Therapeutics and Biogen MA. AV consults for Adverum Biotechnologies. MEP consults for Spark Therapeutics. Susanne Kohl consults for Novartis AG. CA consults for Novartis AG, Janssen Pharmaceuticals and Santen. The rest of the authors have no conflicts of interest to disclose.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)