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SYSTEMATIC REVIEW article

Front. Neurol.

Sec. Neuro-Ophthalmology

Volume 16 - 2025 | doi: 10.3389/fneur.2025.1639913

This article is part of the Research TopicAdvances in Understanding Visual Disorders Linked to Cortical DysfunctionView all 5 articles

Selective serotonin reuptake inhibitors (SSRIs) for amblyopia treatment: A systematic review and meta-analysis of randomized controlled trials

Provisionally accepted
Ehtesham  ShamsherEhtesham Shamsher1Luisa  SaccaroLuisa Saccaro2Victor  Barreiros PungirumVictor Barreiros Pungirum3Nghi  Bao TranNghi Bao Tran4Omar  A H A AlghaithOmar A H A Alghaith5Fatemeh  KhabazianzadehFatemeh Khabazianzadeh6Holly  BridgeHolly Bridge7Betina  IpBetina Ip7*
  • 1Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  • 2Universidade de Mogi das Cruzes, Mogi das Cruzes, Brazil
  • 3Universidad de Buenos Aires Facultad de Medicina, Buenos Aires, Argentina
  • 4Debreceni Egyetem Altalanos Orvostudomanyi Kar, Debrecen, Hungary
  • 5University College London Institute of Ophthalmology, London, United Kingdom
  • 6Mashhad University of Medical Sciences Khatam-al-Anbia Hospital, Mashhad, Iran
  • 7University of Oxford Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom

The final, formatted version of the article will be published soon.

Introduction: 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. Methods: 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 2 statistics.Results: 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 Log MAR, 95%CI 0.04-0.14, p=0.0004), the extent of improvement was not clinically significant. SSRIs did not have any effect on VEPs.While SSRIs significantly improved the 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.

Keywords: Amblyopia, Strabismus, Anisometropia, Fluoxetine, Citalopram, SSRIs

Received: 03 Jun 2025; Accepted: 31 Jul 2025.

Copyright: © 2025 Shamsher, Saccaro, Barreiros Pungirum, Tran, Alghaith, Khabazianzadeh, Bridge and Ip. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Betina Ip, University of Oxford Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom

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