Factors associated with rapid improvement in visual acuity in patients with Leber’s hereditary optic neuropathy after gene therapy
Open accessAbstract
Purpose: To analyse the factors associated with rapid and significant improvement in visual acuity in patients with Leber's hereditary optic neuropathy (LHON) after gene therapy and explain the theory of this improvement. Methods: We recruited 149 patients with LHON, who underwent gene therapy, and divided them into two groups according to the absence or presence of rapid and significant visual acuity improvements within 3 days of treatment. A bivariate logistic regression model was used to analyse relevant factors including age, the period between onset and treatment, baseline values of best corrected visual acuity (BCVA), visual field index (VFI) and pretreatment average retinal nerve fibre‐layer thickness (GRNFL). The corresponding parameters for the injected and non‐injected eyes were analysed separately. Results: The period between onset and treatment, and pretreatment baseline BCVA was significantly associated with rapid and significant improvement in visual acuity for both, the injected and non‐injected eyes. Moreover, pretreatment baseline VFI and GRNFL were not significantly associated with rapid and significant improvement in visual acuity. Age was significantly associated with rapid and significant improvement in visual acuity of the injected eyes. Conclusion: The period between onset and treatment, and pretreatment baseline BCVA may be important predictors of rapid and significant improvement in visual acuity in patients with LHON after gene therapy.
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Two similar gene therapy programmes led by groups in the USA and China targeted the m.11778G>A mutation in MT-ND4 using a viral vector containing a cDNA coding the human wild-type mitochondrial ND4 protein.
“Two similar gene therapy programmes led by groups in the USA25,26 and China,27–30 have targeted the m.11778G>A mutation in MT-ND4, also using a viral vector containing a cDNA coding the human wild-type mitochondrial ND4 protein.”
From Randomized trial of bilateral gene therapy injection for m.11778G&gt;A <i>MT-ND4</i> Leber optic neuropathy (2023) · cites this paper as [29]
The Study participants section (page unavailable) describes a trial in China treating patients with the MT-ND4 m.11778G>A mutation by injecting AAV2-ND4. The Discussion says the introduced ND4 gene produces functional protein that replaces defective ND4, but our copy does not specify that the vector contains a cDNA coding the human wild-type protein. The separate citations attached to the US programmes are outside this source's attribution. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn 149 patients (mean age 19 years) who received unilateral IVT of rAAV2-ND4, 54 (36%) showed early BCVA improvement; it was bilateral in 32% (n=17), treated eye only in 48% (n=26), and contralateral eye only in 20% (n=11).
“The same group subsequently reported on 149 patients (mean age of 19 years) who received a unilateral IVT of rAAV2-ND4, among whom 54 (36%) showed an early BCVA improvement, which was bilateral for 32% (n ¼ 17), in only the treated eye for 48% (n¼26) and only in the contralateral eye for 20% (n ¼ 11).31”
From Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset (2021) · cites this paper as [31]
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- Authors
- Liu, H., Yuan, J., Zhang, Y., Tian, Z., Li, X., Wang, D., Du, Y., Song, L., & Li, B.
- Affiliations
- Department of Ophthalmology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
- Hubei University of Medicine (CN)
- Tongji Hospital (CN)
- Corresponding author
- Li, Bin
- Venue
- Acta Ophthalmologica
- Publisher
- Wiley
- Published
- 2020-02-24
- Volume
- 98
- Issue
- 6
- Pages
- e730-e733
- ISSN
- 0001-639X (ISSN-L)
- 1755-375X
- 1755-3768
- OpenAlex
- W3007696973
- Cited by
- 35
- References
- 22
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 8 · 2021: 5 · 2020: 4
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Ophthalmologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the National Natural Science Foundation (81770969)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- Leber's hereditary optic neuropathy, gene therapy, visual acuity improvement, predictors of treatment response, time to treatment, best-corrected visual acuity, visual field index, retinal nerve fiber layer thickness, age
- MeSH terms
- Female, Humans, Male, Visual Acuity, Genetic Therapy, Case-Control Studies, Optic Atrophy, Hereditary, Leber
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