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Intraocular methotrexate for epithelial downgrowth: long-term outcomes in a multicentre case series
  1. Mélanie Hébert1,
  2. Ralph Kyrillos1,
  3. Michael E Snyder2,
  4. Richard J Mackool3,
  5. Jasmine H Francis4,5,
  6. Helen K Wu6,
  7. Christopher D Riemann2,
  8. Marie Eve Légaré1
  1. 1 Department of Ophthalmology, Hôpital du Saint-Sacrement, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec, Canada
  2. 2 Cincinnati Eye Institute, Cincinnati, Ohio, USA
  3. 3 Mackool Eye Institute, Astoria, New York, USA
  4. 4 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  5. 5 Department of Ophthalmology, Weill Cornell Medical College, New York, New York, USA
  6. 6 Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, USA
  1. Correspondence to Dr Marie Eve Légaré, Department of Ophthalmology, Centre Hospitalier affilié Universitaire de Québec Hôpital du Saint-Sacrement, Quebec, Canada; marie-eve.legare{at}


Background/Aims Sheet-like type of epithelial downgrowth (EDG) is not easily amenable to surgical excision. We describe long-term outcomes in patients with EDG treated with intraocular methotrexate (MTX).

Methods This is a retrospective, multicentric case series including 10 eyes (nine patients) treated with intraocular MTX for sheet-like EDG. Relevant ocular history, previous EDG treatments, MTX injection regimen, long-term outcomes and complications are reported.

Results All cases were associated with intraocular surgery. Most patients were treated with 400 µm/0.1 mL MTX injections with a starting frequency of two times per week or weekly injections. Mean and SD number of injections per eye was 16±13 injections and duration of follow-up was 54±36 months (range: 7–120 months). Eradication of EDG was achieved in seven eyes of which one required a second MTX treatment course to achieve eradication, while clinical resolution with recurrence was observed in two. One treatment failure occurred despite eight weekly injections which slowed but did not halt EDG progression; the patient later requested that treatments be stopped given difficulty to come to follow-ups. Surface epitheliopathy developed in eight patients and was used to titrate MTX treatment. Six patients also developed endothelial failure.

Conclusion We report the largest case series of diffuse, sheet-like EDG treated with intraocular MTX with follow-ups up to 10 years. Intraocular MTX may be used effectively to achieve eradication of EDG in cases where surgery is not amenable. However, further recommendations to guide treatment remain warranted.

  • Drugs
  • Treatment Medical
  • Treatment Surgery
  • Trauma
  • Cornea

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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  • MH and RK are joint first authors.

  • MH and RK contributed equally.

  • Contributors MH, RK and MEL conceived the work, performed the literature review, acquired, analysed and interpreted the data and drafted and reviewed the manuscript. MES, RJM, JHF, HKW and CDR acquired the data and critically revised the submitted version. All authors approved the final manuscript and agree to be held accountable for all aspects of the work. MEL acts as guarantor for the published work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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