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M. M. Hermann, B. Schröter, M. Diestelhorst; Comparison of Rapamycin and Mitomycin for Reduction of Postoperative Fibrosis After Filtration Surgery in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3199.
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Postoperative fibrosis is a challenge for successful filtration surgery in glaucoma. Mitomycin C is widely used to modulate wound healing but is known to cause significant toxic effects on ocular tissue. Rapamycin (Sirolimus) has a known antifibrotic action on vascular endothelium und cultured human tenon fibroblasts. This study aimed at comparing the effects of Rapamycin and Mitomycin on postoperative fibrosis after filtration surgery in a rabbit model.
24 rabbits (ChBB:CH) received a unilateral subconjunctival injections of Rapamycin (200µl, 1mg/ml) immediately after filtrating glaucoma surgery and 1 week after sugery. 24 control eyes received episcleral sponge application of 100 µl Mitomycin C (0.2 mg/ml, 4 min) during surgery. Antifibrotic efficacy was established by clinical response and histological examination. A bleb survival analysis based on IOP measurements was used to compare clinical response of Rapamycin and Mitomycine C. Sucessful filtration surgery was defined as a lowering of IOP by 4 mmHg or more from baseline. Baseline was assessed for each eye by repeated rebound tonometry before surgery. Animals were sacrificed four weeks after surgery for histological examination.
Mean baseline IOP was 19.7 ± 1.2 mmHg. Mean IOP one day after surgery was 10.5 ± 3.0 mmHg and did not differ significantly between eyes treated with Mitomycin or Rapamycin (t-test, p=0.27). Mean bleb survival (Kaplan Meier) was 24.7 ±1.1 days with Mitomycin and 23.7 ± 1.2 days with Rapamycin. The difference was insignificant (Log Rank test, p>0.5). Histological comparison of the surgical area using blind scoring revealed a milder fibrosis and a higher number of blood vessels in eyes treated with Rapamycin (Mann-Whitney-U-Test, p<0.05).
Rapamycin showed an antifibrotic efficiency comparable to Mitomycin in this animal model for filtration surgery. Rapamycin is a promising approach to control postoperative fibrosis in patients undergoing filtration surgery. Whether a sufficient long-term effect in human eyes using repeated subconjunctival injections of Rapamycin can be achieved remains to be elucidated.
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