Developing novel anti-fibrotic therapeutics to modulate post-surgical wound healing in glaucoma: big potential for small molecules

Ocular fibrosis leads to significant visual impairment and blindness in millions of people worldwide, and is one of the largest areas of unmet need in clinical ophthalmology. The antimetabolites, mitomycin C and 5-fluorouracil, are the current gold standards used primarily to prevent fibrosis after glaucoma surgery, but have potentially blinding complications like tissue damage, breakdown and infection. This review thus focuses on the development of new classes of small molecule therapeutics to prevent post-surgical fibrosis in the eye, especially in the context of glaucoma filtration surgery. We discuss recent advances and innovations in ophthalmic wound healing research, including antibodies, RNAi, gene therapy, nanoparticles, liposomes, dendrimers, proteoglycans and small molecule inhibitors. We also review the challenges involved in terms of drug delivery, duration of action and potential toxicity of new anti-fibrotic agents in the eye.