Five-year results after AAV2-REP1 gene therapy for choroideremia

Abstract

Purpose : To assess the long-term safety and efficacy of a recombinant adeno-associated viral vector expressing REP1 (AAV2-REP1) in choroideremia patients.

Methods : For the six patients who received single subfoveal injection of AAV2-REP1, five of them were followed up for up to five years. The long-term safety was evaluated by the ophthalmic examination, spectral-domain optical coherence tomography (SD-OCT), and short-wavelength fundus autofluorescence (FAF). Functional and structural changes were determined by best-corrected visual acuity (BCVA) change from baseline in treated eyes compared to untreated eyes, sensitivity change in microperimetry, preserved retinal pigment epithelium (RPE) area measured from FAF, central macular thickness measured from SD-OCT and central V4e kinetic visual field measured with Octopus.

Results : One subject experienced a localized intraretinal immune response that resulted in significant loss of preserved RPE in FAF. Another subject experienced exacerbation of peripheral retinoschisis observed by OCT. One subject had a constant≥15-letter BCVA gain in the treated eye through one to four and half years after treatment, while one subject had a one time≥15-letter BCVA improvement in the untreated eye. Microperimetry sensitivity showed constant decline in both treated eyes and untreated eyes without significant difference between groups. Central (≤30 dg) V4e kinetic visual field was noted to decline at a similar rate between the treated and untreated eyes. For preserved RPE area, four out of five subjects had similar slopes of decline in both treated and untreated eyes while for one subject preserved RPE in treated eye was found to decline slower than the untreated eye (p=0.02). For central macular thickness measured from OCT, four subjects had similar declines in the rate between the treated eye and untreated eyes; one subjects had significantly more rapid central macular thickness decline (p<0.01) in the treated eyes possibly due to observed adverse event.

Conclusions : The intraretinal inflammation and regional RPE loss triggered by AAV2-REP1 gene therapy stabilized after two years. The potential long-term benefits for AAV2-REP1 gene therapy include improvement in visual acuity, preservation in RPE in small portion of the study subjects (1/6, respectively) though more data is needed to support this statement.

This is a 2021 ARVO Annual Meeting abstract.

 

VA over the follow-up peroid.

 

FAF and OCT data for the postoperative intraretinal inflammation case.