Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies
| Status: | Terminated |
|---|---|
| Conditions: | Cardiology, Ocular |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Ophthalmology |
| Healthy: | No |
| Age Range: | 18 - 85 |
| Updated: | 1/25/2018 |
| Start Date: | September 2011 |
| End Date: | August 2012 |
Evaluation of the Utility of Intravitreal Methotrexate in Patients With Recalcitrant Diabetic Macular Edema in an Open Label, Nonrandomized, Uncontrolled, Interventional Pilot Trial
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.
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.
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.
Inclusion Criteria:
- Adult patients (18 years and older) with clinically significant macular edema (CSME)
with visual acuity less than 20/60 to Hand motion in the study eye.
- Patients should have persistent CSME three months after laser therapy or three months
after intraocular injection of Avastin or triamcinolone. These interventions could be
multiple or combined.
- Optical coherence tomography (OCT) scan demonstrating more than 275 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), ≤ 8.5HbA1c that has been
evaluated in the last 3 months.
- Ability to undergo contraceptive protection during and 3 months after intraocular
injections.
- Clear demonstration (in female patients) of commitment to avoid pregnancy and a
negative urine pregnancy test at baseline for women of childbearing potential.
- Clear understanding of teratogenic potential of MTX.
Exclusion Criteria:
- History of allergy to MTX.
- An ocular condition is present such that, in the opinion of the investigator, visual
acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy,
pigment abnormalities, dense subfoveal hard exudates, nonretinal condition.
- An ocular condition is present (other than diabetes) that, in the opinion of the
investigator, might affect macular edema or alter visual acuity during the course of
the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease,
neovascular glaucoma, epiretinal membrane, etc.).
- An eye treated for Glaucoma
- Eyes that underwent vitrectomy
- History of intraocular malignancies.
- Intraocular surgery with the prior 3 months.
- Recent significant change in diabetic medications.
- Insulin usage less than a year.
- Life threatening co morbidities such as cancer under therapy.
- Use of oral, intravenous, periocular or intraocular corticosteroids (steroids) in
prior 3 months.
- Liver function that exceeds three times the upper limit of normal at baseline, or
within 6 weeks of that appointment.
- 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.
- Any major surgery within the last 30 days
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