Purpose:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
Keywords: wound healing • anterior segment • clinical laboratory testing