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Toxic Corneal Epitheliopathy After Intravitreal Methotrexate and Its Treatment With Oral Folic Acid

Gorovoy, Ian MD; Prechanond, Tidarat MD; Abia, Maravillas MD; Afshar, Armin R. MD, MBA; Stewart, Jay M. MD

doi: 10.1097/ICO.0b013e3182910106
Case Report

Purpose: To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma.

Methods: We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate.

Results: In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid.

Conclusions: Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

Department of Ophthalmology, University of California, San Francisco, San Francisco, CA.

Reprints: Jay M. Stewart, University of California, San Francisco, Department of Ophthalmology, 10 Koret Way, K301, San Francisco, CA 94143-0730 (e-mail:

Supported by That Man May See, Inc and the Research to Prevent Blindness.

The authors have no funding or conflicts of interest to disclose.

Received February 11, 2013

Accepted March 07, 2013

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.