Durable recovery from amblyopia with donepezil
Abstract An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-34891-5 |
| _version_ | 1797795638410215424 |
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| author | Carolyn Wu Eric D. Gaier Bharti R. Nihalani Sarah Whitecross Takao K. Hensch David G. Hunter |
| author_facet | Carolyn Wu Eric D. Gaier Bharti R. Nihalani Sarah Whitecross Takao K. Hensch David G. Hunter |
| author_sort | Carolyn Wu |
| collection | DOAJ |
| description | Abstract An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16 years; range 9–37 years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12 weeks. Donepezil dosage was started at 2.5 or 5.0 mg based on age and increased by 2.5 mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4 weeks prior for a maximum dosage of 7.5 or 10 mg. Participants < 18 years of age further patched the dominant eye. The primary outcome was visual acuity in the amblyopic eye at 22 weeks, 10 weeks after treatment was discontinued. Mean amblyopic eye visual acuity improved 1.2 lines (range 0.0–3.0), and 4/16 (25%) improved by ≥ 2 lines after 12 weeks of treatment. Gains were maintained 10 weeks after cessation of donepezil and were similar for children and adults. Adverse events were mild and self-limited. Residual amblyopia improves in older children and adults treated with donepezil, supporting the concept that the critical window of visual cortical plasticity can be pharmacologically manipulated to treat amblyopia. Placebo-controlled studies are needed. |
| first_indexed | 2024-03-13T03:21:02Z |
| format | Article |
| id | doaj.art-4ff45b1787f94c3691a42fd3cedf1dc9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T03:21:02Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4ff45b1787f94c3691a42fd3cedf1dc92023-06-25T11:17:53ZengNature PortfolioScientific Reports2045-23222023-06-011311910.1038/s41598-023-34891-5Durable recovery from amblyopia with donepezilCarolyn Wu0Eric D. Gaier1Bharti R. Nihalani2Sarah Whitecross3Takao K. Hensch4David G. Hunter5Department of Ophthalmology, Boston Children’s HospitalDepartment of Ophthalmology, Boston Children’s HospitalDepartment of Ophthalmology, Boston Children’s HospitalDepartment of Ophthalmology, Boston Children’s HospitalCenter for Brain Science, Department of Molecular Cellular Biology, Harvard UniversityDepartment of Ophthalmology, Boston Children’s HospitalAbstract An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16 years; range 9–37 years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12 weeks. Donepezil dosage was started at 2.5 or 5.0 mg based on age and increased by 2.5 mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4 weeks prior for a maximum dosage of 7.5 or 10 mg. Participants < 18 years of age further patched the dominant eye. The primary outcome was visual acuity in the amblyopic eye at 22 weeks, 10 weeks after treatment was discontinued. Mean amblyopic eye visual acuity improved 1.2 lines (range 0.0–3.0), and 4/16 (25%) improved by ≥ 2 lines after 12 weeks of treatment. Gains were maintained 10 weeks after cessation of donepezil and were similar for children and adults. Adverse events were mild and self-limited. Residual amblyopia improves in older children and adults treated with donepezil, supporting the concept that the critical window of visual cortical plasticity can be pharmacologically manipulated to treat amblyopia. Placebo-controlled studies are needed.https://doi.org/10.1038/s41598-023-34891-5 |
| spellingShingle | Carolyn Wu Eric D. Gaier Bharti R. Nihalani Sarah Whitecross Takao K. Hensch David G. Hunter Durable recovery from amblyopia with donepezil Scientific Reports |
| title | Durable recovery from amblyopia with donepezil |
| title_full | Durable recovery from amblyopia with donepezil |
| title_fullStr | Durable recovery from amblyopia with donepezil |
| title_full_unstemmed | Durable recovery from amblyopia with donepezil |
| title_short | Durable recovery from amblyopia with donepezil |
| title_sort | durable recovery from amblyopia with donepezil |
| url | https://doi.org/10.1038/s41598-023-34891-5 |
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