The technique draws on personal experience with gene augmentation therapy by subretinal injection in patients with choroideremia, RPE65 mutation-associated retinal dystrophy, and X-linked retinitis pigmentosa. Only 2 surgeons initially performed RPE65 gene therapy in the Phase 3 clinical trial leading to drug approval in the United States and the European Union. 1 As new surgeons begin to use the commercially available product voretigene neparvovec-rzyl for RPE65 mutation–related inherited retinal dystrophy (IRD) or to participate in clinical trials, there is a need for education in best practices for subretinal injection. Clinical trials are currently listed on clinicaltrials. gov for choroideremia, 2–5 X-linked retinitis pigmentosa (RPGR genotype), autosomal recessive retinitis pigmentosa (MERTK genotype), achromatopsia (CNGA3 and CNGB3), Stargardt disease (ABCA4), Leber congenital amaurosis (CEP290), and Usher syndrome type 1B (MY07A), with several additional subretinal gene therapies in the pipeline.

There are few options with currently available technology for delivery of gene therapy for IRD other than subretinal injection. Intravitreal injection of gene therapy is simpler to perform but is predicted to be useful only for optic nerve or retinal diseases affecting primarily the retinal nerve fiber layer, ganglion cell layers, and inner retinal layers (eg, Leber hereditary optic neuropathy and X-linked retinoschisis RS1) due to barriers presented by the internal limiting membrane and the retinal tissue. 6, 7 Microcatheters advanced into suprachoroidal space of rabbits achieved transfection with adeno-associated virus 2 (AAV2) vector as demonstrated by GFAP expression 8; however, there is concern that therapy delivered to the suprachoroidal space would be more difficult to target, require higher doses, be more likely to disseminate to unwanted systemic sites, or fail to penetrate outer blood retinal barrier at the level of the retinal pigment epithelium and Bruch membrane. Therefore, subretinal injection is likely to remain the procedure of choice for the near future. Technological innovations may facilitate surgical delivery of vector to the subretinal space. 9–12