Abstract
ABSTRACTGlaucoma 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.
Highlights
IntroductionTrabeculectomy was introduced by Cairns in 1968 and remains the most commonly performed procedure for the treatment of glaucoma.[1,2] The introduction of antifibrotic
Trabeculectomy was introduced by Cairns in 1968 and remains the most commonly performed procedure for the treatment of glaucoma.[1,2] The introduction of antifibroticThe Role of Vascular endothelial growth factor (VEGF) and Anti-VEGF in Glaucoma Filtration SurgeryDue to the nonspecific inhibitory activity and continued risk of failure associated with antifibrotic agents, other forms of more selective wound modulation with acceptable side effects have been explored in recent years
Niforushan et al[8] conducted a prospective, randomized study assessing the efficacy of subconjunctival bevacizumab (2.5 mg/0.1 ml; 18 eyes) at the end of trabeculectomy com pared with mitomycin C (MMC)-augmented trabeculectomy (0.002% for 3 minutes; 18 eyes) and demonstrated significantly lower intraocular pressure (IOP) control postoperatively in the MMC group compared to the bevacizumab group (10 mm Hg vs 14 mm Hg respectively, p < 0.001)
Summary
Trabeculectomy was introduced by Cairns in 1968 and remains the most commonly performed procedure for the treatment of glaucoma.[1,2] The introduction of antifibrotic. In a mouse model of glaucoma filtration surgery, the authors reported improved surgical outcome with increasing bleb survival and bleb area following intracameral injection of anti-PIGF This was associated with a significant reduction in cellular proliferation, inflammation and angiogenesis during the first postoperative days after surgery, and with a decrease in collagen deposition at the later stages. The same investigators assessed the effects of subcon junctivally-administered trastuzumab in the rabbit model of filtration surgery.[29] Trastuzumab is a humanized mono clonal antibody against the extracellular domain of the human epidermal growth factor 2 (HER2) It is most widely used in the treatment of overexpression of HER2 in early or metastatic breast cancer, its mechanism of action is not completely understood.[30] When compared to trabe culectomy combined with intrascleral application of MMC (0.4 mg/ml for 3 minutes), trabeculectomy with a subcon junctival injection of trastuzumab (1.2 mg/0.1 ml) showed comparable numbers of mononuclear cells and fibroblasts in the filtration site on histology (p > 0.05). They observed that eyes that received Cxn[43] AsODN had reduced Cx43 upregulation at 8 and 24 hours post-injection, which led to less myofibroblast upregulation at days 5 and 21 and reduced scarring at day 21 compared to controls
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