Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies
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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Primary would be 30% decrease in one subfield thickness on OCT 4 weeks after the last intraocular injection [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Secondary would be increase in VA two lines or more at the end of one month after the last intraocular injection. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
- Secondary would be significant clinical improvement (judged at the slit lamp exam using a 90D lens) in macular edema at the end of one month after the last intraocular injection. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
|Study Start Date:||September 2011|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Single arm pilot study with no placebo
Drug: Methotrexate intravenous 25mg/ml
Intravitreal MTX 400 ug delivered once or twice (based on the therapeutic response) over a period of 2 months maximum. Total dosage 400ug in each dose. Statistical analysis would not be applicable in this small sample.
|United States, North Carolina|
|Wake Forest Baptist Health Eye Center|
|Winston Salem, North Carolina, United States, 27157|
|Principal Investigator:||Shree K Kurup, MD||Wake Forest Baptist Health Eye Center|