Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy

Hum Gene Ther. 2018 Dec;29(12):1428-1437. doi: 10.1089/hum.2018.014. Epub 2018 Jul 24.


Previously, results at 2 years after subretinal injection of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in eight adults and four children with retinal degeneration caused by RPE65 mutations were reported. Now, results at 5 years after treatment in 11 of these subjects are reported. Subjects received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of two dose levels, and were followed for 5 years after treatment. The primary safety outcomes were ocular and non-ocular adverse events. Efficacy outcomes included changes in best corrected visual acuity, static perimetry hill of vision measurements for the central 30° (V30), and total (VTOT) visual field and kinetic perimetry visual field area. The only adverse events reported during years 3, 4, and 5 were minor intercurrent illnesses. Pediatric subjects had improvement in visual acuity and static perimetry in the treated eye, sometimes with a smaller improvement in the untreated eye, during the first 2 years of the study that persisted during years 3-5, with no consistent changes in kinetic perimetry during the study. Most adult subjects had no consistent changes in visual acuity or static perimetry during the study. Three adult subjects with markedly abnormal baseline kinetic visual field area had improvement in the treated eye during the first 1-2 years after treatment, but the absolute magnitude of the improvement was small and was not sustained at subsequent visits. There were no clinically significant adverse events. Visual acuity and static perimetry testing results suggest that treating patients at a younger age is associated with better visual function outcomes during 5 years after treatment.

Trial registration: NCT00749957.

Keywords: AAV; Leber congenital amaurosis; RPE65; gene therapy; retinal degeneration.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Dependovirus / genetics*
  • Dependovirus / metabolism
  • Female
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Injections, Intraocular
  • Leber Congenital Amaurosis / genetics
  • Leber Congenital Amaurosis / metabolism
  • Leber Congenital Amaurosis / pathology
  • Leber Congenital Amaurosis / therapy*
  • Male
  • Mutation*
  • Patient Safety
  • Prospective Studies
  • Retina / metabolism
  • Retina / pathology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy*
  • Treatment Outcome
  • Visual Acuity / physiology
  • Visual Fields / physiology
  • cis-trans-Isomerases / genetics*
  • cis-trans-Isomerases / metabolism


  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Associated data