Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate
T. Sakamoto, D. Soriano, J. Nassaralla, T. L. Murphy, A. Oganesian, C. Spee, D. R. Hinton and S. J. Ryan
Doheny Eye Institute, University of Southern California, School of Medicine, Los Angeles.
OBJECTIVE: To examine the effect of indomethacin, a cyclooxygenase (CO)
inhibitor, on laser-induced subretinal neovascularization (SRN) in the
monkey. The CO pathway of arachidonic acid metabolism plays an important
role in angiogenesis, and the inhibition of CO is known to inhibit
angiogenesis in the cornea and in certain tumors. MATERIALS AND METHODS: A
cannula was implanted into the vitreous cavity of 11 eyes of six monkeys
and connected to an osmotic minipump. Indomethacin (25 micrograms/d) was
delivered into the vitreous through the cannula for 14 days (seven eyes).
Vehicle alone was injected for 14 days as a control (four eyes). Argon
laser photocoagulation was then performed (eight spots at the posterior
pole in each eye) to induce SRN. Fundus photographs and fluorescein
angiograms were taken periodically to document the evolution of SRN. Light
and electron microscopic examination was performed on two eyes of each
group 8 weeks after photocoagulation. RESULTS: Subretinal
neovascularization developed from 2 to 4 weeks after photocoagulation. The
incidence of SRN, indicated by fluorescein leakage, was significantly lower
(P < .05) in the group treated with indomethacin (14.3%, eight of 56
lesions) than in the control group (37.5%, 12 of 32 lesions). After 8
weeks, no fluorescein leakage was found in either the control or
indomethacin-treated groups. Scar formation was found on histologic
examination in both groups. No histologic evidence of indomethacin toxicity
was seen in the adjacent retina. CONCLUSIONS: Intravitreal administration
of indomethacin inhibits the formation of laser-induced SRN in monkey eyes.
This is consistent with the participation of the CO pathway in the process
of SRN formation and suggests that this pathway could be a potential target
in the treatment of SRN.
