Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2

Ophthalmology. 2013 Jun;120(6):1283-91. doi: 10.1016/j.ophtha.2012.11.048. Epub 2013 Mar 6.


Objective: The aim of this study was to show the clinical data of long-term (3-year) follow-up of 5 patients affected by Leber congenital amaurosis type 2 (LCA2) treated with a single unilateral injection of adeno-associated virus AAV2-hRPE65v2.

Design: Clinical trial.

Participants: Five LCA2 patients with RPE65 gene mutations.

Methods: After informed consent and confirmation of trial eligibility criteria, the eye with worse visual function was selected for subretinal delivery of adeno-associated virus (AAV2-hRPE65v2). Subjects were evaluated before and after surgery at designated follow-up visits (1, 2, 3, 14, 30, 60, 90, 180, 270, and 365 days, 1.5 years, and 3 years) by complete ophthalmic examination. Efficacy for each subject was monitored with best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex.

Main outcome measures: Best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex.

Results: The data showed a statistically significant improvement of best-corrected visual acuity between baseline and 3 years after treatment in the treated eye (P<0.001). In all patients, an enlargement of the area of visual field was observed that remained stable until 3 years after injection (average values: baseline, 1058 deg(2) vs. 3 years after treatment, 4630 deg(2)) and a reduction of the nystagmus frequency compared with baseline at the 3-year time point. Furthermore, a statistically significant difference was observed in the pupillary constriction of the treated eye (P<0.05) compared with the untreated eye in 3 patients at 1- and 3-year time points. No patients experienced serious adverse events related to the vector in the 3-year postinjection period.

Conclusions: The long-term follow-up data (3 years) on the 5-patient Italian cohort involved in the LCA2 gene therapy clinical trial clearly showed a stability of improvement in visual and retinal function that had been achieved a few months after treatment. Longitudinal data analysis showed that the maximum improvement was achieved within 6 months after treatment, and the visual improvement was stable up to the last observed time point.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Dependovirus / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Injections, Intraocular
  • Leber Congenital Amaurosis / genetics
  • Leber Congenital Amaurosis / physiopathology
  • Leber Congenital Amaurosis / therapy*
  • Male
  • Mutation
  • Reflex, Pupillary / physiology
  • Tomography, Optical Coherence
  • Transfection
  • Visual Acuity / physiology
  • Visual Fields / physiology
  • Young Adult
  • cis-trans-Isomerases / genetics*


  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Supplementary concepts

  • Amaurosis congenita of Leber, type 2