Wound Healing Modulation in Glaucoma Filtration Surgery– Conventional Practices and New Perspectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II)

Abstract

Glaucoma filtration surgery is regularly performed for the treatment of glaucoma and trabeculectomy is often regarded as the ‘gold standard' glaucoma operation. The biggest risk of failure of the operation is bleb scarring. The advent of antifibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5FU) has vastly prolonged the longevity of the bleb, but concerns remain regarding the potential increase in postoperative complications. More selective therapeutic targets have therefore been explored. One of these is vascular endothelial growth factor (VEGF) inhibition. VEGF inhibition has a role not only in subconjunctival angiogenesis inhibition but also it has direct anti-fibrotic properties. Newer pharmacological compounds and materials have also been developed in recent years in attempt to modulate the wound healing in different ways after glaucoma surgery. These include physical barriers to scarring and vehicles for sustained release of pharmacological agents, and early promising results have been demonstrated. This two-part review will provide a discussion of the application of anti-fibrotic agents in glaucoma filtration surgery and evaluate the newer agents that have been developed.How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glau coma Filtration Surgery–Conventional Practices and New Pers pectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II). J Curr Glaucoma Pract 2014;8(2):46-53.

ZD6474 attenuates TGF-β1-induced fibrosis in human Tenon fibroblasts and inhibits neovascularization via AKT-mTOR signaling pathway

“…GFS is to deliberately open an extra aqueous outflow pathway in trabecular meshwork to decrease IOP effectively, but there are still numerous potential complications post-operatively. After GFS, the re-blockage of the pathway due to scar formation (severe fibroblasts proliferation, extra ECM accumulation), resulting in upregulating IOP again is very common [ 22 ]. During the early stage of wound healing post-operatively, excessive TGF‐β promotes fibrosis perhaps via recruiting fibroblasts and increase fibroblast proliferation [ 23 ].…”

Nox4 Facilitates TGFβ1-Induced Fibrotic Response in Human Tenon’s Fibroblasts and Promotes Wound Collagen Accumulation in Murine Model of Glaucoma Filtration Surgery

“…Excessive post-operative scarring is a major cause of failure in GFS [ 19 ]. In this study, we demonstrate that TGFβ1-induced Nox4 expression plays an important role in collagen synthesis by using HTFs.…”

MEK inhibition prevents TGF‑β1‑induced myofibroblast transdifferentiation in human tenon fibroblasts

“…Therefore, targeting the inhibition of fibroblast activation has been regarded as a critical intervention strategy for fibrotic diseases. In ocular tissue, although certain anti-mitotic agents including MMC and 5-FU have been employed to contract trabeculectomy-associated subconjunctival fibroblasts (21,22), they often result in serious postoperative complications, including bleb leakage, hypotony maculopathy and endophthalmitis (23,24). The data indicating that U0126 potently prevents HTF activation indicates an alternative targeting approach for this disease.…”