The
goal is to develop agents that are selective for neovascular tissue-
the new abnormal blood vessels in macular degeneration- with acceptable
therapeutic indices and means of delivery.
To date, no pharmacologic agents have met these criteria.
Alpha-interferon blocks vascular endothelial proliferation and migration in
the laboratory. A randomized,
placebo-controlled, multicenter clinical, double-blind clinical
trial of alpha-interferon for subfoveal choroidal neovascular membranes
showed increased visual loss in the treated group with the
higher doses (6 million IU) in comparison with the control group.
Thus, alpha-interferon may be ineffective or even harmful.
Isotrentioin
is one of the most potent known
inhibitors of blood vessel growth.
This agent may act by modulating extracellular matrix components
that are required for growth of abnormal blood vessels.
Isotrenetoin was tested in a small phase II clinical trial-
no significant beneficial effects were observed in 17 eyes with
choroidal neovascular membranes.
Corticosteroids are known to inhibit blood vessel growth.
Intraocular steroids were found to inhibit experimental formation
of abnormal blood vessels. In an uncontrolled study, intravitreal triamcinolone produced
beneficial effects in 11 of 30 eyes.
Antimetabolites are anticancer drugs that inhibit blood vessel growth.
A combination steroid-antimetabolite drug (triamcinolone/5-fluorouracil)
was found to be effective in inhibiting experimental choroidal neovascularization
in a model of macular degeneration.
No clinical studies have been pursued as of yet.
Thalidomide inhibits postreceptor signal transduction for growth factor
stimulation of endothelial cells.
A prospective clinical trial in patients with wet macular
degeneration was halted after the drug was found to cause significant
adverse side effects, such as peripheral neuropathy.
Agouron (AG3340) is a matrix metalloprotease inhibitor which
blocks the extracellular matrix remodeling required for blood vessel
growth. Experimentally,
it decreased new blood vessel growth in the retina of mice.
It has been used in clinical trials for cancer treatment.
A phase II, randomized, double-masked, placebo controlled multi-center
clinical trial is underway. |
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