{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T03:18:12Z","timestamp":1781579892335,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Amblyopia is a neurodevelopmental visual disorder treated with occlusion or pharmacological penalization of the dominant, non-amblyopic eye in early childhood. After early childhood, efficacy of occlusion therapy is limited due to a reduction in neuronal plasticity, and no mainstay clinical treatment is available. Selective serotonin reuptake inhibitors (SSRIs) have been hypothesized to enhance neuroplasticity in the adult brain, thereby facilitating improvements in amblyopia. We aimed to perform a systematic review and meta-analysis evaluating the effect of SSRIs on patients with amblyopia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched Pubmed, EMBASE, and Cochrane Central for randomized controlled trials (RCTs) and controlled observational studies comparing an SSRI with placebo in patients with amblyopia. Outcomes of interest were visual acuity (VA) change and visual evoked potential (VEP) change (P100 amplitude and latency). Statistical analysis was performed using the web version of RevMan by calculating the mean difference between groups (MD). Heterogeneity was assessed with Cochrane Q test and I<jats:sup>2<\/jats:sup> statistics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four RCTs and 139 patients were included. 55% patients received SSRIs. Three studies used fluoxetine and one study used citalopram as the intervention. While SSRIs use statistically improved VA (MD 0.09 logMAR, 95% CI 0.04\u20130.14, <jats:italic>p<\/jats:italic>\u202f=\u202f0.0004), the extent of improvement was not clinically significant. SSRIs did not have any effect on VEPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>While SSRIs significantly improved VA in patients, the increase was not clinically significant as it represents less than one line of improvement on the Snellen chart. Given the minimal change in VA, it may be necessary to combine SSRIs with other modalities of intervention to demonstrate a clinically significant effect. Secondary endpoints that capture effects at the level of the retina and the brain would provide knowledge of physiological mechanisms that can improve future therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p>CRD42025633077, <jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD42025633077<\/jats:uri>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1639913","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T05:28:33Z","timestamp":1755754113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Selective serotonin reuptake inhibitors for amblyopia treatment: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.3389","volume":"16","author":[{"given":"Ehtesham","family":"Shamsher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Saccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Barreiros","family":"Pungirum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghi Bao","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A. H. A.","family":"Alghaith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Khabazianzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Bridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Betina","family":"Ip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"819998","DOI":"10.3389\/fped.2022.819998","article-title":"The global prevalence of amblyopia in children: a systematic review and Meta-analysis","volume":"10","author":"Hu","year":"2022","journal-title":"Front Pediatr"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"342","DOI":"10.22336\/rjo.2020.56","article-title":"A systematic review of amblyopia prevalence among the children of the world","volume":"64","author":"Mostafaie","year":"2020","journal-title":"Rom J Ophthalmol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1093\/cercor\/bhj110","article-title":"Strabismic suppression is mediated by inhibitory interactions in the primary visual cortex","volume":"16","author":"Sengpiel","year":"2006","journal-title":"Cereb Cortex"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"6855","DOI":"10.1523\/JNEUROSCI.14-11-06855.1994","article-title":"Interocular suppression in the visual cortex of strabismic cats","volume":"14","author":"Sengpiel","year":"1994","journal-title":"J Neurosci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/eye.1996.54","article-title":"The neural basis of suppression and amblyopia in strabismus","volume":"10","author":"Sengpiel","year":"1996","journal-title":"Eye"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12886-020-01442-9","article-title":"Efficacy of interventions for amblyopia: a systematic review and network meta-analysis","volume":"20","author":"Li","year":"2020","journal-title":"BMC Ophthalmol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1097\/OPX.0b013e3181a7b3e5","article-title":"The optical treatment of amblyopia","volume":"86","author":"Moseley","year":"2009","journal-title":"Optom Vis Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"R936","DOI":"10.1016\/j.cub.2014.05.063","article-title":"Plasticity of the visual cortex and treatment of amblyopia","volume":"24","author":"Sengpiel","year":"2014","journal-title":"Curr Biol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"12830","DOI":"10.1038\/s41598-018-31169-z","article-title":"Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia","volume":"8","author":"Huttunen","year":"2018","journal-title":"Sci Rep"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"14964","DOI":"10.1523\/JNEUROSCI.4812-10.2010","article-title":"Removing brakes on adult brain plasticity: from molecular to behavioral interventions","volume":"30","author":"Bavelier","year":"2010","journal-title":"J Neurosci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1126\/science.1150516","article-title":"The antidepressant fluoxetine restores plasticity in the adult visual cortex","volume":"320","author":"Vetencourt","year":"2008","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1038\/s41433-019-0360-z","article-title":"Oral fluoxetine in the management of amblyopic patients aged between 10 and 40 years old: a randomized clinical trial","volume":"33","author":"Sharif","year":"2019","journal-title":"Eye"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"104009","DOI":"10.1016\/j.jaapos.2024.104009","article-title":"Fluoxetine as a possible treatment for adult amblyopia: results of a double-blind, randomized, placebo-controlled trial","volume":"28","author":"Mirmohammadsadeghi","year":"2024","journal-title":"J AAPOS"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"5857243","DOI":"10.1155\/2019\/5857243","article-title":"The effect of combined patching and citalopram on visual acuity in adults with amblyopia: a randomized, crossover, placebo-controlled trial","volume":"2019","author":"Lagas","year":"2019","journal-title":"Neural Plast"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"b2535","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref18","first-page":"4","article-title":"Mechanism of action of antidepressant medications","volume":"60","author":"Feighner","year":"1999","journal-title":"J Clin Psychiatry"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.conb.2008.05.009","article-title":"Critical period revisited: impact on vision","volume":"18","author":"Morishita","year":"2008","journal-title":"Curr Opin Neurobiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1016\/j.ophtha.2015.01.002","article-title":"A randomized trial of levodopa as treatment for residual amblyopia in older children","volume":"122","author":"Repka","year":"2015","journal-title":"Ophthalmology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"10161","DOI":"10.1038\/s41598-023-34891-5","article-title":"Durable recovery from amblyopia with donepezil","volume":"13","author":"Wu","year":"2023","journal-title":"Sci Rep"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"E017","DOI":"10.1017\/S0952523817000244","article-title":"Animal models of amblyopia","volume":"35","author":"Mitchell","year":"2018","journal-title":"Vis Neurosci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10633-016-9553-y","article-title":"ISCEV standard for clinical visual evoked potentials: (2016 update)","volume":"133","author":"Odom","year":"2016","journal-title":"Doc Ophthalmol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00429-021-02273-0","article-title":"Investigating the neurochemistry of the human visual system using magnetic resonance spectroscopy","volume":"227","author":"Ip","year":"2022","journal-title":"Brain Struct Funct"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1162\/imag_a_00256","article-title":"The relationship between visual acuity loss and GABAergic inhibition in amblyopia","volume":"2","author":"Ip","year":"2024","journal-title":"Imaging Neurosci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1177\/03010066231178664","article-title":"Investigating the human binocular visual system using multi-modal magnetic resonance imaging","volume":"52","author":"Bridge","year":"2023","journal-title":"Perception"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"949395","DOI":"10.3389\/fnhum.2022.949395","article-title":"Visual cortical \u03b3\u2212aminobutyric acid and perceptual suppression in amblyopia","volume":"16","author":"Mukerji","year":"2022","journal-title":"Front Hum Neurosci"},{"key":"ref28","year":"2025"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/09273972.2025.2478078","article-title":"Optical coherence tomography (OCT) parameters in amblyopia","author":"Chedid","year":"2025","journal-title":"Strabismus"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/jov.23.1.14","article-title":"Applications and implications for extended reality to improve binocular vision and stereopsis","volume":"23","author":"Levi","year":"2023","journal-title":"J Vis"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"R1122","DOI":"10.1016\/j.cub.2015.10.026","article-title":"A cycling lane for brain rewiring","volume":"25","author":"Lunghi","year":"2015","journal-title":"Curr Biol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1002\/acn3.698","article-title":"A new counterintuitive training for adult amblyopia","volume":"6","author":"Lunghi","year":"2019","journal-title":"Annal. Clin. Transl. Neurol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1639913\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T05:28:34Z","timestamp":1755754114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1639913\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":32,"alternative-id":["10.3389\/fneur.2025.1639913"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1639913","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]},"article-number":"1639913"}}