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Topical application of methotrexate for inhibition of corneal angiogenesis
A M Joussen1, F E Kruse, H E Völcker
1Technical University of Aachen (RWTH), Department of Ophthalmology, Pauwelsstrasse 30, D-57052 Aachen, Germany. JoussenA@aol.com
Purpose:
Methotrexate (MTX) is a folic acid antagonist used in chemotherapy regimens. Additional therapeutic applications have been suggested based on effect as an immuno-modulating drug in systemic rheumatoid disease and associated uveitis. Since chronic inflammatory disease is often associated with a neovascular response, we investigated the use of MTX for treatment of corneal angiogenesis.
Methods:
Neovascularizations were induced by fibroblast growth factor in a corneal pocket model. Vessels were examined biomicroscopically. MTX was applied topically to rabbit corneas in a concentration of 0.2 mg/day. MTX level was measured in aqueous humor and plasma.
Results:
On day 9 the vascularized area was 12.0+/-6.9 mm(2) in control eyes and significantly smaller, 2. 2+/-1.86 mm(2), in treated eyes. Treated animals showed no local side effects such as epithelial defects. Although therapeutic levels were measured in the aqueous humor, MTX could not be detected in the serum of treated animals.
Conclusion:
The antiangiogenic mechanism of MTX might be due to inhibition of both macrophage invasion during early angiogenesis and endothelial cell proliferation. The high levels in the aqueous humor indicate a possible application of topical MTX for inflammations of the anterior segment of the eye.