Abstract
Purpose :
Clinical trials for X-linked retinitis pigmentosa often assess retinal structure using Optical Coherence Tomography (OCT) and function using microperimetry to evaluate initial eligibility and endpoints. Therefore, we seek to determine which parameters might be most sensitive in screening new potential patients for enrolment.
Methods :
Thirty-one patients with confirmed RPGR mutations (62 eyes) attending Oxford Eye Hospital were included in this retrospective analysis. Outer retinal structure was investigated by measuring the remaining ellipsoid zone (EZ) and external limiting membrane (ELM) on OCT. Visual function was evaluated by using 10-2 microperimetry mean sensitivity (MS).
Results :
The median age of RPGR patients was 31 years (IQR:22,39). For the right and left eyes respectively, the median EZ through the foveal section was 921μm (IQR:607,1570) and 865μm (IQR:508,1442) and ELM was 2056μm (IQR:1336,2764) and 1860μm (IQR:1152,2680). The median MS was 2.0dB (IQR:0.4,5.4) and 1.1dB (IQR:0.1,5.4). Linear mixed model regression analysis showed that EZ was significantly positively correlated to ELM (p<0.001, R=0.931). EZ and ELM were significantly correlated with MS with a exponential relationship (p<0.001, R=0.71 and 0.72, respectively). Using the exponential equation of regression line, EZ below approximately 600μm (RE=637μm (95%CI:397-877), LE=586μm (95%CI:356-817)) results in MS of approximately 0dB. There was high degree of inter-eye symmetry for progression of EZ, ELM and MS. Age was significantly correlated with the analyzed parameters (p<0.001), though with low R for each of them.
Conclusions :
EZ may comprise a surrogate biomarker for prediction of visual function in X-linked RP caused by RPGR and in turn, identification of appropriate patients for enrolment in clinical trials. Age plays a role in predicting potential biomarkers and visual function, however it should not be used to preclude patients for gene therapy due to the poor correlation and heterogeneity of disease onset.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.