Evaluation of nintedanib as a new postoperative antiscarring agent in experimental extraocular muscle surgery

Aim: To investigate the efficacy of nintedanib on reducing postoperative inflammation, fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide (TA).

Methods: Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed. They were randomized to receive one of the following treatments: 0.9% normal saline, one of 1-, 5-, and 10 µmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1, 2, 3, 5, and 7, and TA immediately after surgery. As a control group, unoperated left eyes (n=6) were used. On the 28^th day, six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes, fibrosis and adhesion. Transforming growth factor beta, matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.

Results: Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline (sham) group. Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10 µmol nintedanib group. Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis. Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion. The expressions of transforming growth factor beta, alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.

Conclusion: Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery. Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to Steroids. Further investigation is needed to prove antiadhesive effect of nintedanib.