Longitudinal Structure-Function Evaluation in a Patient with CDHR1-Associated Retinal Dystrophy: Progressive Visual Function Loss with Retinal Remodeling

Retinal dystrophies related to damaging variants in the cadherin-related family member 1 (CDHR1) gene are rare and phenotypically heterogeneous. Here, we report a longitudinal (three-year) structure-function evaluation of a patient with a CDHR1-related retinal dystrophy.

A 14-year-old girl was evaluated between 2019 and 2022. An ophthalmological assessment, including color vision, perimetry, electroretinography, and multimodal imaging of the retina, was performed periodically every six months. Next-generation sequencing disclosed two likely pathogenic/pathogenic variants in the CDHR1 gene, in compound heterozygosity, confirmed by segregation analysis.

At first examination, the patient showed a cone-rod pattern retinal dystrophy. Over follow-up, there was a decline of visual acuity and perimetric sensitivity (by ≥0.3 and 0.6 log units, respectively). Visual loss was associated with a progressive increase in inner retinal thickness (by 30%). Outer retina showed no detectable changes over the follow-up.

The results indicate that, in this patient with a CDHR1-related cone-rod dystrophy, the progression to severe visual loss was paralleled by a progressive inner retinal thickening, likely a reflection of remodeling. Inner retinal changes over time may be functionally relevant in view of the therapeutic attempts based on gene therapy or stem cells to mitigate photoreceptor loss.