Intraocular methotrexate for epithelial downgrowth: long-term outcomes in a multicentre case series

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.

[1]  J. Oh,et al.  Corneal Epithelial Toxicity after Intravitreal Methotrexate Injection for Vitreoretinal Lymphoma: Clinical and In Vitro Studies , 2020, Journal of clinical medicine.

[2]  C. Peris-Martínez,et al.  Intracameral 5-fluorouracil and viscous dispersive viscoelastic for diffuse epithelial downgrowth management in aphakia. , 2020, International journal of ophthalmology.

[3]  Indrayuda Indrayuda,et al.  TOXIC , 2020, Jurnal Sendratasik.

[4]  Lai Jiang,et al.  Transcorneal Cryotherapy and Descemet Membrane Endothelial Keratoplasty to Treat Epithelial Downgrowth and Corneal Decompensation After Cataract Surgery. , 2020, Cornea.

[5]  T. Sivagnanasithiyar,et al.  Using an excel spreadsheet to convert Snellen visual acuity to LogMAR visual acuity , 2020, Eye.

[6]  K. Ohshima,et al.  Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis , 2019, The American journal of surgical pathology.

[7]  David J. Wilson,et al.  Intravitreal Methotrexate for Recurrent Epithelial Downgrowth. , 2019, JAMA ophthalmology.

[8]  Frances Wu,et al.  Successful Treatment of Epithelial Ingrowth with Intravitreal Methotrexate. , 2019, Ophthalmology.

[9]  Liang Liu,et al.  Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. , 2018, European journal of medicinal chemistry.

[10]  Phoebe Lin,et al.  Treatment of Epithelial Downgrowth Masquerading as Unilateral Hypopyon Uveitis in a HLA−B27+ Individual , 2018, Ocular immunology and inflammation.

[11]  J. Chung,et al.  Descemet Membrane Endothelial Keratoplasty for Epithelial Downgrowth After Clear Corneal Cataract Surgery , 2016, Eye & contact lens.

[12]  Amin Ahem,et al.  Successful treatment of epithelial downgrowth with endoscopic photocoagulation and intracameral 5-fluorouracil after prolonged limbal wound leak. , 2018, International journal of ophthalmology.

[13]  A. Tonnel,et al.  Endothelial cells , 1991 .

[14]  M. Snyder,et al.  Partial Lamellar Sclerokeratouvectomy for Management of Epithelial Downgrowth , 2016, Cornea.

[15]  K. Ghasemi Falavarjani,et al.  Effect of Intravitreal Injection of Methotrexate on Human Corneal Endothelial Cells , 2016, Cornea.

[16]  M. Goldberg,et al.  Epithelial Downgrowth after Intraocular Surgery Treated with Intracameral 5-Fluorouracil , 2015, Case reports in ophthalmological medicine.

[17]  D. Wakefield,et al.  Tracing the Fate of Limbal Epithelial Progenitor Cells in the Murine Cornea , 2015, Stem cells.

[18]  Ricardo M. Santaella,et al.  Clinical Course and Origin of Epithelium in Cases of Epithelial Downgrowth After Descemet Stripping Automated Endothelial Keratoplasty , 2014, Cornea.

[19]  C. Eberhart,et al.  5-Fluorouracil for Epithelial Downgrowth After Descemet Stripping Automated Endothelial Keratoplasty , 2013, Cornea.

[20]  J. Stewart,et al.  Toxic Corneal Epitheliopathy After Intravitreal Methotrexate and Its Treatment With Oral Folic Acid , 2013, Cornea.

[21]  Y. Liu,et al.  PHARMACOKINETIC COMPARISON OF KETOROLAC AFTER INTRACAMERAL, INTRAVITREAL, AND SUPRACHOROIDAL ADMINISTRATION IN RABBITS , 2012, Retina.

[22]  I. Goldman,et al.  The antifolates. , 2012, Hematology/oncology clinics of North America.

[23]  P. Rosenfeld,et al.  NOVEL METHOD FOR ANALYZING SNELLEN VISUAL ACUITY MEASUREMENTS , 2010, Retina.

[24]  T. Siegal,et al.  Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience , 2008, British Journal of Ophthalmology.

[25]  R. Revoltella,et al.  Epithelial stem cells of the eye surface , 2007, Cell proliferation.

[26]  Carol S. Yu,et al.  Treatment of Cystic Epithelial Downgrowth With Intralesional Administration of Mitomycin C , 2005, Cornea.

[27]  P. Kertes,et al.  Bilateral epithelial downgrowth managed in one eye with intraocular 5-fluorouracil. , 2002, Archives of ophthalmology.

[28]  David J. Wilson,et al.  Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. , 2002, Ophthalmology.

[29]  J. Haller,et al.  Resolution of epithelial ingrowth in a patient treated with 5-fluorouracil. , 2002, American journal of ophthalmology.

[30]  S. Chen,et al.  Epithelial and fibrous downgrowth: mechanisms of disease. , 2002, Ophthalmology clinics of North America.

[31]  K Bandeen-Roche,et al.  Functional status and quality of life measurement among ophthalmic patients. , 1994, Archives of ophthalmology.

[32]  R. Weinreb,et al.  Glaucoma secondary to epithelial downgrowth and 5-fluorouracil. , 1990, Ophthalmic surgery.

[33]  D. Albert,et al.  Epithelial downgrowth: a 30-year clinicopathological review. , 1989, The British journal of ophthalmology.

[34]  R. E. Smith,et al.  Specular microscopy of epithelial downgrowth. , 1978, Archives of ophthalmology.