Phenotypic Characterization in Two Patients with Identified Rhodopsin Gene Mutation: Impact of Retinal Degeneration on Cortical Structure

Abstract

Purpose: : To characterize the phenotype of two patients with rod dystrophy due to identified rhodopsin gene mutations, both at the retinal and cortical level.

Methods: : The two patients with novel rhodopsin gene mutations in highly conserved regions (p.Tyr60His and p.Arg69Cys located in exon 1), were submitted to color fundus photographs and optical coherence tomography (Cirrus - OCT). Psychophysical tests included subjective color vision assessment (Cambridge Colour Test), static perimetry (Humphrey 10-2), and microperimetry. We also performed clinical electrophysiology (pattern ERG, multifocal ERG and full field ERG - including an ERG 9Hz protocol to detect residual responses, S-cone ERG and ON-/OFF- ERG). We also used magnetic resonance imaging and Freesurfer software to measure and analyze cortical thickness, cortical volume and surface area of Brodmann Areas. These data (n = 4 hemispheres) were compared with age-matched controls (n = 8 hemispheres). Statistical analysis was performed using Mann-Whitney test at an α level of 0.05.

Results: : Both patients showed a significant reduction in RNFL and retinal thickness measured by OCT (well below 3 SD as compared to the normative database). Concerning electrophysiological results, multifocal ERG showed a very significant reduction in P1 wave amplitude for all rings (well below 3 SD). Pattern ERG and full field ERG responses were absent in both patients.Only one patient was eligible for psychophysics: his visual field was limited to the central 5 degrees (mean sensitivity = 5 dB) and we found evidence for damage of all chromatic (cone) pathways. Local cortical thickness was preserved in visual areas. However, patients’ hemispheres showed reduced volume in V1 (p=0.042) and V2 (p=0.011) as well as in surface area in V2 (p=0.001) and MT (p=0.027). Interestingly, increased cortical thickness in regions of the motor cortex was detected (p=0.017, for BA4a; p=0.042, for BA6).

Conclusions: : Our results suggest that although visual cortical thickness may be preserved in retinitis pigmentosa the overall size of visual representations is reduced. This is consistent with the notion of shrinkage of peripheral vision and its cortical substrates during development in this genetic condition of early onset.

Keywords: retinitis • visual cortex • pathology: human