Abstract
Purpose :
Three-dimensional indicator in spectral-domain optical coherence tomography (SD-OCT) to evaluate and compare the retinal structural changes in X-linked retinoschisis (XLRS) patients with different genotypes remains unexplored. The study aimed to investigate a promising SD-OCT indicator and establish a link between the phenotype and genotype in XLRS.
Methods :
All genetically confirmed 37 XLRS patients underwent complete ophthalmic examination, including visual acuity (VA), fundus examination, electroretinogram (ERG), and SD-OCT. SD-OCT parameters of central foveal thickness (CFT), cyst cavity volume (CCV), and photoreceptor outer segment (PROS) length were assessed for 64 eyes from 33 patients. CCV was defined as a summation of the area of cyst cavities in sequential b-scans. It was measured automatically by a self-developed software system. Structural changes of protein associated with missense variants were quantified by molecular dynamics (MD). Pearson’s correlation was applied in clinical data analysis and genotype-phenotype analysis for missense variants.
Results :
The 37 XLRS patients were identified with 27 different RS1 variants, of which, c.336_337insT (p.L113Sfs*8) is novel. The mean of CCV was 7.27±8.01 mm3. In clinical data analysis, CCV was significantly correlated with CFT (R=0.66 [p<0.01]). In genotype-phenotype analysis, CCV was significantly correlated with the structural effect on protein of mutational changes referred to wildtype, including root-mean-square deviation (ΔRMSD, R=0.34 [p=0.04]), solvent accessible surface area (ΔSASA, R=0.38 [p=0.02]), and surface hydrophobic area (R=0.37 [p=0.03]). Additionally, the amplitude of scotopic 3.0 ERG a wave and b wave were significantly correlated with the percentage change of β-strand in secondary structure (Δβ-strand, R=-0.58 [p<0.01] and R=-0.53 [p<0.01], respectively).
Conclusions :
We proposed that CCV could be a promising indicator to quantify the structural disorganization of the XLRS retina in three-dimensions. The self-developed software system offered an approach to calculate CCV automatically. Moreover, MD-involved genotype-phenotype analysis implied an association between the predicted protein structural alteration and the severity of XLRS as measured by the CCV and/or ERG.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.