Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies

Condition(s) targeted: Diabetic Macular Edema

Intervention: Methotrexate intravenous 25mg/ml (Drug)

Phase: N/A

Status: Not yet recruiting

Sponsored by: Wake Forest University

Official(s) and/or principal investigator(s):
Shree K Kurup, MD, Principal Investigator, Affiliation: Wake Forest University Eye Center

Overall contact:
Lori Cooke, RN, BSN, Phone: 336-716-6116, Email: lcooke@wfubmc.edu

It is well known that blindness is one of the most feared disabilities expressed by patients in the United States. Estimates of the economic impact of visual disability in the current population exceed 30 million US dollars in this country alone. The reasons for this figure are many; however age related macular degeneration (ARMD), diabetic retinopathy, glaucoma and uveitis are responsible for the majority of permanent visual disability and hence the costs in both quality of life and placing an economic burden on society. Research that may help reverse various abnormal biological responses that lead to or worsen clinical manifestations of diabetic retinopathy would be valuable.

The most common reason for decreased vision in diabetic retinopathy is macular edema. Current approaches to macular edema include FDA approved interventions such as laser and better underlying control of the disease and co morbid conditions. 'Off label' interventions include intravitreal triamcinolone and bevacizumab, both of which have been demonstrated to be efficacious; at least in the short term (weeks) but carry significant risks. Surgical approaches are still controversial and have not shown long term benefits. Unfortunately, there are subsets of patients resistant to any of the above therapies. Intravitreal therapies utilizing methotrexate 400 ug (MTX) have been used for other ophthalmologic conditions associated with inflammation driven macular edema. bevacizumab an anti VEGF agent has been utilized in diseases other than macular degeneration with a favorable effect. It is known that certain similar inflammatory mediators play a role in diabetic macular edema. It would be logical to evaluate the efficacy of MTX an anti inflammatory anti metabolite at low concentrations in diabetic patients with macular edema who have failed conventional FDA approved and well studied off label therapies that involve laser and/or intravitreal drugs.

Official title: Evaluation of the Utility of Intravitreal Methotrexate in Patients With Recalcitrant Diabetic Macular Edema in an Open Label, Nonrandomized, Uncontrolled, Interventional Pilot Trial

Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Primary outcome: Primary would be 40% decrease in central subfield thickness on OCT at the end of three months after the last intraocular injection.

Secondary outcome:

Secondary would be increase in VA two lines or more at the end of three months after the last intraocular injection.

Secondary would be significant clinical improvement (judged at the slit lamp exam using a 90D lens) in macular edema at the end of three months.

Secondary outcomes would be 25 % decrease in subfield thickness at the end of three weeks after the last intraocular injection.

Minimum age: 16 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult patients with clinically significant macular edema (CSME) with visual acuity

less than 20/80 to Hand motion in the study eye.

- Patients should have persistent CSME three months after focal laser or three months

after intraocular triamcinolone. These interventions could be multiple or combined.

- Optical coherence tomography (OCT) scan demonstrating more than 225 microns retinal

thickness in central subfield of study eye.

- Ability to understand study instructions, interventions and potential complications.

- History of reasonably controlled Diabetes mellitus (DM), < 7. 5 HbA1c.

- Ability to undergo contraceptive protection during and 6 months after intraocular

injections.

- Clear demonstration (in female patients) of commitment to avoid pregnancy.

- Clear understanding of teratogenic potential of MTX.

Exclusion Criteria:

- History of allergy to MTX.

- History of intraocular malignancies.

- Intraocular surgery with the prior 6 months.

- Recent significant change in diabetic medications.

- Insulin usage less than a year.

- Life threatening co morbidities such as cancer under therapy.

- Use of intravenous, periocular or intraocular corticosteroids (steroids) in prior 6

months.

- Children less than 16 years of age.

- Pregnant females.

- Vitreous hemorrhage (active) in study eye

- Anticipation of the need for laser pan retinal photocoagulation in the next 6 months.

- Media opacities

- Herpetic disease of cornea

- Corneal dystrophy with significant corneal edema.

Lori Cooke, RN, BSN, Phone: 336-716-6116, Email: lcooke@wfubmc.edu

Wake Forest University Eye Center, Winston Salem, North Carolina 27157, United States

Related publications:

Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, Klein R, Tielsch JM, Vijan S, Saaddine J. The economic burden of major adult visual disorders in the United States. Arch Ophthalmol. 2006 Dec;124(12):1754-60. Erratum in: Arch Ophthalmol. 2007 Sep;125(9):1304.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Iida T, Sakamoto T, Nishida K. Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone acetonide on persistent diffuse diabetic macular edema. Am J Ophthalmol. 2008 May;145(5):854-61. Epub 2008 Mar 6.

Vasconcelos-Santos DV, Nehemy PG, Schachat AP, Nehemy MB. Secondary ocular hypertension after intravitreal injection of 4 mg of triamcinolone acetonide: incidence and risk factors. Retina. 2008 Apr;28(4):573-80.

Hartley KL, Smiddy WE, Flynn HW Jr, Murray TG. Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema. Retina. 2008 Mar;28(3):410-9.

Querques G, Delle Noci N. Ultrastructure of the vitreomacular interface in full-thickness idiopathic macular holes: a consecutive analysis of 100 cases. Am J Ophthalmol. 2006 Nov;142(5):892; author reply 892-3. Epub 2006 Sep 7. No abstract available.

Ghajarnia M, Kurup S, Eller A. The therapeutic effects of intravitreal bevacizumab in a patient with recalcitrant idiopathic polypoidal choroidal vasculopathy. Semin Ophthalmol. 2007 Apr-Jun;22(2):127-31.

Last updated: October 28, 2008