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    This phase 2 study reports the use of a high-dose gene therapy for choroideremia.

    Study design

    The open-label clinical trial included 6 men with genetically confirmed advanced choroideremia. The eye with poorer vision received a subfoveal injection of an adeno-associated virus 2 Rab escort protein 1 (AAV-REP1; 1011 genome particles in 0.1 mL) and was compared with the untreated fellow eye. Patients were followed for 24 months.


    The mean ETDRS baseline best-corrected visual acuity (BCVA) was 65 letters in treated eyes and 77 letters in untreated eyes. At 2 years, 2 treated eyes improved by 5 and 10 letters; 1 untreated eye improved by 4 letters. The remaining eyes were within 2 letters of baseline.

    There was no change in microperimetry scores, visual field, color vision or contrast sensitivity. No serious adverse events were noted; most adverse events were expected and attributed to vitrectomy with subretinal fluid injection surgery.


    Although AAV2-REP1 may be able to improve vision in advanced cases of choroideremia, most patients in this trial did not have any discernable benefits. It is unclear whether genetic variants, surgical factors or advanced-stage disease influence outcomes.

    Clinical significance

    This phase 2 trial demonstrates proof of concept that AAV2-REP1 gene therapy may help improve vision in patients with advanced choroideremia. This study contributed several notable advances in drug administration, such as the use of intraoperative OCT guidance to help confirm location. This level of precise gene delivery is critical for these trials and will likely remain important when subretinal gene therapy is used in clinical practice. The authors also utilized an automated injection system attached to the vitrectomy machine because they believed this was more accurate than manual dosing.