title: Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2.
abstract: 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.
  
  
  METHODS
  Clinical trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology, Second University of Naples, Naples, Italy. franctes@tin.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Testa
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.forename: Settimio
authors.initials: S
authors.lastname: Rossi
authors.forename: Eric A
authors.initials: EA
authors.lastname: Pierce
authors.forename: Paolo
authors.initials: P
authors.lastname: Melillo
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marshall
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Surace
authors.forename: Junwei
authors.initials: J
authors.lastname: Sun
authors.forename: Carmela
authors.initials: C
authors.lastname: Acerra
authors.forename: J Fraser
authors.initials: JF
authors.lastname: Wright
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wellman
authors.forename: Katherine A
authors.initials: KA
authors.lastname: High
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D056965:Injections, Intraocular; D057130:Leber Congenital Amaurosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009154:Mutation; D012025:Reflex, Pupillary / Q000502:physiology; D041623:Tomography, Optical Coherence; D014162:Transfection; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
chemical_list: D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase