PMID- 37982768
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240305
IS  - 2164-2591 (Electronic)
IS  - 2164-2591 (Linking)
VI  - 12
IP  - 11
DP  - 2023 Nov 1
TI  - Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With 
      Retinal Degeneration: A Systematic Review and Meta-Analysis.
PG  - 24
LID - 10.1167/tvst.12.11.24 [doi]
LID - 24
AB  - PURPOSE: This systematic review evaluates the safety and efficacy of ocular gene 
      therapy using adeno-associated virus (AAV). METHODS: MEDLINE, Embase, Cochrane 
      Central Register of Controlled Trials, and ClinicalTrials.gov were searched 
      systematically for controlled or non-controlled interventional gene therapy 
      studies using key words related to retinal diseases, gene therapy, and AAV 
      vectors. The primary outcome measure was safety, based on ocular severe adverse 
      events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based 
      on best corrected visual acuity (BCVA) and improvements in visual sensitivity and 
      systemic involvement following ocular delivery. Pooling was done using a 
      DerSimonian Laird random effects model. Risk of bias was assessed using the 
      Cochrane Risk of Bias Tool, version 1. RESULTS: Our search identified 3548 
      records. Of these, 80 publications met eligibility criteria, representing 28 
      registered clinical trials and 5 postmarket surveillance studies involving AAV 
      gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber 
      hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), 
      retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, 
      AAV therapy vectors were associated with a cumulative incidence of at least one 
      SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often 
      associated with the surgical procedure rather than the therapeutic vector itself. 
      Poor or inconsistent reporting of adverse events (AEs) were a limitation for the 
      meta-analysis. The proportion of patients with any improvement in BCVA and visual 
      sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), 
      respectively. Systemic immune involvement was associated with a cumulative 
      incidence of 31% (95% CI = 21% to 42%). CONCLUSIONS: AAV gene therapy vectors 
      appear to be safe but the surgical procedure required to deliver them is 
      associated with some risk. The large variability in efficacy can be attributed to 
      the small number of patients treated, the heterogeneity of the population and the 
      variability in dosage, volume, and follow-up. TRANSLATIONAL RELEVANCE: This 
      systematic review will help to inform and guide future clinical trials.
FAU - Sobh, Mohamad
AU  - Sobh M
AD  - Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa 
      Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Lagali, Pamela S
AU  - Lagali PS
AD  - Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada.
FAU - Ghiasi, Maryam
AU  - Ghiasi M
AD  - Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa 
      Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Montroy, Joshua
AU  - Montroy J
AD  - Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa 
      Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Dollin, Michael
AU  - Dollin M
AD  - Department of Ophthalmology, University of Ottawa, University of Ottawa Eye 
      Institute, Ottawa, Ontario, Canada.
FAU - Hurley, Bernard
AU  - Hurley B
AD  - Department of Ophthalmology, University of Ottawa, University of Ottawa Eye 
      Institute, Ottawa, Ontario, Canada.
FAU - Leonard, Brian C
AU  - Leonard BC
AD  - Department of Ophthalmology, University of Ottawa, University of Ottawa Eye 
      Institute, Ottawa, Ontario, Canada.
AD  - Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, 
      Ontario, Canada.
FAU - Dimopoulos, Ioannis
AU  - Dimopoulos I
AD  - Department of Ophthalmology, University of Ottawa, University of Ottawa Eye 
      Institute, Ottawa, Ontario, Canada.
FAU - Lafreniere, Mackenzie
AU  - Lafreniere M
AD  - Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa 
      Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Fergusson, Dean A
AU  - Fergusson DA
AD  - Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa 
      Hospital Research Institute, Ottawa, Ontario, Canada.
AD  - Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
FAU - Lalu, Manoj M
AU  - Lalu MM
AD  - Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa 
      Hospital Research Institute, Ottawa, Ontario, Canada.
AD  - Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, 
      Ontario, Canada.
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, 
      Ontario, Canada.
AD  - Departments of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, 
      Ontario, Canada.
FAU - Tsilfidis, Catherine
AU  - Tsilfidis C
AD  - Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada.
AD  - Department of Ophthalmology, University of Ottawa, University of Ottawa Eye 
      Institute, Ottawa, Ontario, Canada.
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, 
      Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
PL  - United States
TA  - Transl Vis Sci Technol
JT  - Translational vision science & technology
JID - 101595919
SB  - IM
MH  - Humans
MH  - *Retinal Degeneration/therapy
MH  - Dependovirus/genetics
MH  - *Macular Degeneration/drug therapy
MH  - *Retinitis Pigmentosa
MH  - Genetic Therapy/adverse effects
PMC - PMC10668613
COIS- Disclosure: M. Sobh, None; P.S. Lagali, None; M. Ghiasi, None; J. Montroy, None; 
      M. Dollin, None; B. Hurley, None; B.C. Leonard, None; I. Dimopoulos, None; M. 
      Lafreniere, None; D.A. Fergusson, None; M.M. Lalu, None; C. Tsilfidis, None
EDAT- 2023/11/20 13:41
MHDA- 2023/11/27 12:43
PMCR- 2023/11/20
CRDT- 2023/11/20 10:34
PHST- 2023/11/27 12:43 [medline]
PHST- 2023/11/20 13:41 [pubmed]
PHST- 2023/11/20 10:34 [entrez]
PHST- 2023/11/20 00:00 [pmc-release]
AID - 2793037 [pii]
AID - TVST-23-5558 [pii]
AID - 10.1167/tvst.12.11.24 [doi]
PST - ppublish
SO  - Transl Vis Sci Technol. 2023 Nov 1;12(11):24. doi: 10.1167/tvst.12.11.24.