Evidence map›Paper›PMID 35271811›Full record

ArticleAmerican journal of ophthalmology2022

Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups.

Byron L Lam, William J Feuer, Janet L Davis, Vittorio Porciatti, Hong Yu, Robert B Levy, Elizabeth Vanner, John Guy

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of ophthalmology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02161380 (An Open-label Dose Escalation Study of an Adeno-associated Virus Vector), which is not on this map. Cited by 25 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02161380 phase1completednot on this map

An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA

TypeinterventionalSponsorByron LamRan2014 to 2025Enrolled28ConditionsLeber's Hereditary Optic NeuropathyArmsinjection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),, injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med), injection of scAAV2-P1ND4v2 2.4 X10e10vg (High), injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 3 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Article
  7. Review
  8. Review
  9. Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Leber's hereditary optic neuropathy - current status of idebenone and gene replacement therapies.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Byron L LamFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address: blam@med.miami.edu.
William J FeuerFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
Janet L DavisFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
Vittorio PorciattiFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
Hong YuFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
Robert B LevyFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
Elizabeth VannerFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
John GuyFrom the Bascom Palmer Eye Institute (B.L.L., W.J.F., J.L.D., V.P., H.Y., E.V., J.G.) and Department of Microbiology and Immunology (R.B.L.), University of Miami Miller School of Medicine, Miami, Florida, USA.
University of Miami · US

Funding

Shared Equipment ModuleP30EY014801 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Victor L Perez · 2004 to 2026
$12.2M
Leber's Hereditary Optic Neuropathy: Gene Therapy Clinical TrialU10EY023558 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GUY, JOHN · 2014 to 2018
$5.8M
Biostatistics Center for Leber's Hereditary Optic Neuropathy: Gene Therapy TrialU10EY024247 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI FEUER, WILLIAM JACK · 2014 to 2018
$566k
Lebers Hereditary Optic Neuropathy: Gene TherapyUG1EY023558 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LAM, BYRON L · 2019 to 2022
$0k
NEI NIH HHS P30 EY014801NEI NIH HHS U10 EY023558NEI NIH HHS U10 EY024247NEI NIH HHS UG1 EY023558
6 · The paper itself

Abstract

purposeTo assess safety of gene therapy in G11778A Leber hereditary optic neuropathy (LHON).

designPhase 1 clinical trial.

methodsSetting: single institution.

participantsPatients with G11778A LHON and chronic bilateral visual loss >12 months (group 1, n = 11), acute bilateral visual loss <12 months (group 2, n = 9), or unilateral visual loss (group 3, n = 8).

interventionunilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high, and higher doses to worse eye for groups 1 and 2 and better eye for group 3. OUTCOME MEASURES: Best-corrected visual acuity (BCVA), adverse events, and vector antibody responses. Mean follow-up was 24 months (range, 12-36 months); BCVAs were compared with a published prospective natural history cohort with designated surrogate study and fellow eyes.

resultsIncident uveitis (8 of 28, 29%), the only vector-related adverse event, resulted in no attributable vision sequelae and was related to vector dose: 5 of 7 (71%) higher-dose eyes vs 3 of 21 (14%) low-, medium-, or high-dose eyes (P < .001). Incident uveitis requiring treatment was associated with increased serum AAV2 neutralizing antibody titers (p=0.007) but not serum AAV2 polymerase chain reaction. Improvements of ≥15-letter BCVA occurred in some treated and fellow eyes of groups 1 and 2 and some surrogate study and fellow eyes of natural history subjects. All study eyes (BCVA ≥20/40) in group 3 lost ≥15 letters within the first year despite treatment.

conclusionsG11778A LHON gene therapy has a favorable safety profile. Our results suggest that if there is an efficacy effect, it is likely small and not dose related. Demonstration of efficacy requires randomization of patients to a group not receiving vector in either eye.

Indexed as

Optic Atrophy, Hereditary, LeberDependovirusDNA, MitochondrialElectroretinographyGenetic TherapyGenetic VectorsHumansNADH DehydrogenaseProspective StudiesRetinal Ganglion CellsTomography, Optical CoherenceVision DisordersVisual AcuityVisual FieldsDNA, MitochondrialNADH Dehydrogenase

Identifiers

PMID35271811
PMCPMC9444871
OpenAlexW4221034281

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.