Abstract
Purpose :
Gene therapy is an appealing therapeutic strategy for both inherited and non-inherited retinal conditions. Development of intraocular clinical and subclinical inflammation has been documented and may limit the success of therapy. However, the overall prevalence of gene-therapy associated uveitis (GTAU) in retinal gene therapies has not been established.
Methods :
Cochrane CENTRAL, ClinicalTrials.gov and EUDRACT databases were queried for peer and non-peer reviewed publications (June 2023). The primary outcome was prevalence of intraocular inflammation after gene therapy. Data were extracted by one author (TB) and transformed into per study prevalence. Meta-analysis of proportions was undertaken using the metafor library in R and the generalized linear mixed model (GLMM). Multiple linear regression was used to analyse administration route and vector type as independent variables and prevalence of intraocular inflammation as the dependent variable using the lm function in R. Risk of bias per study was assessed qualitatively using the ORBIT II criteria for harms. Studies were graded P3 where no primary outcome data was available 12 months after completion.
Results :
135 clinical trials were included. 18 studies were graded P3. Sufficient data for analysis could be obtained for 1690 patients across 60 trials. Non-peer reviewed sources accounted for 45% of the included data in the meta-analysis. The overall prevalence of gene-therapy related intraocular inflammation was 0.21 (0.20 to 0.23, 95% CI, n = 1690 patients) . There was statistically significant heterogeneity between studies for differing conditions (I2 = 75%, p = 0.01). The prevalence of inflammation in patients who received intravitreal treatments was 0.52 (95% CI 0.47 to 0.57); subretinal treamtents, 0.24 (95% CI 0.20 to 0.28); and suprachoroidal treatments, 0.21 (95% CI 0.14 to 0.29).
Conclusions :
Intravitreal delivery of viral vectors was associated with greater prevalence of intraocular inflammation after gene therapy than subretinal and suprachoroidal administration. 10% of trials may not be aligned with FDA reporting requirements.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.