Journal Highlights
Ophthalmology Retina, January 2022
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Gange et al. report the observation of perifoveal chorioretinal atrophy in eyes that underwent subretinal injection of the gene therapy voretigene neparvovec (VN; Luxturna) for RPE65-mediated Leber congenital amaurosis (LCA). They recommend further study to isolate the factors that may predispose patients to this previously undescribed complication.
For this study, the authors performed a retrospective chart review on all patients who received a subretinal VN injection at four of the 10 clinical sites currently treating patients with the gene therapy. Patients were identified as having perifoveal chorioretinal atrophy if 1) the areas of atrophy were not directly related to the touchdown site of the subretinal cannula, and 2) the area of atrophy grew larger over time. Main outcome measures included change in visual acuity (VA), visual fields, and location of atrophy relative to subretinal bleb position.
All told, 10 patients (18 eyes) at the four sites participating in this study were found to have developed atrophy, and the atrophy was bilateral in eight of the 10 patients. The patients’ mean age was 11.6 years (range, 5-20 years), and six were male.
The atrophy was first noticeable from one week to one year following surgery (mean, 4.7 months post-op), and it progressively enlarged in all cases up to the last follow-up examination (mean follow-up, 11.3 months; range, 4-18 months).
Atrophy developed within and outside the area of the subretinal bleb in 10 eyes, exclusively within the area of the bleb in seven eyes, and exclusively outside the bleb in one eye. VA improved in 12 eyes, held steady in three, and worsened in three. Overall, however, there was no significant change in mean VA before and after treatment (p = .45); the authors noted that this was likely due to the atrophy sparing the fovea.
In their discussion, the authors cited several potential factors that may have contributed to the atrophy, including direct toxicity of the vector to the photoreceptors and retinal pigment epithelium, an inflammatory or immune response to the vector, and surgical technique. It also is possible that the atrophy described in this study is consistent with preexisting ocular factors, such as myopia, or with the natural history of the disease, independent of the treatment, they said.
Given these uncertainties, further study is needed. This is particularly critical not only for LCA but also for the growing number of retinal gene therapy trials and their expansion to such conditions as age-related macular degeneration and diabetic retinopathy, the authors noted.
The original article can be found here.