ISRCTN12125882 - Influence of topical anti-VEGF (Ranibizumab) on the outcome of filtration surgery for glaucoma - Study Protocol (original) (raw)
Related papers
Investigative Ophthalmology & Visual Science, 2009
PURPOSE. Filtration failure due to excessive postoperative scarring remains a major problem after glaucoma surgery. The authors have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab, can reduce postoperative scar formation and improve surgical outcome. METHODS. The levels of VEGF in samples of aqueous humor were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis. RESULTS. VEGF levels were increased significantly in the aqueous humor of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits. CONCLUSIONS. VEGF was upregulated in the aqueous humor of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring process after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved
Current and Future Techniques in Wound Healing Modulation after Glaucoma Filtering Surgeries
The Open Ophthalmology Journal, 2016
Filtering surgeries are frequently used for controlling intraocular pressure in glaucoma patients. The long-term success of operation is intimately influenced by the process of wound healing at the site of surgery. Indeed, if has not been anticipated and managed accordingly, filtering surgery in high-risk patients could end up in bleb failure. Several strategies have been developed so far to overcome excessive scarring after filtering surgery. The principal step involves meticulous tissue handling and modification of surgical technique, which can minimize the severity of wound healing response at the first place. However, this is usually insufficient, especially in those with high-risk criteria. Thus, several adjuvants have been tried to stifle the exuberant scarring after filtration surgery. Conventionally, corticosteroids and anti-fibrotic agents (including 5-fluorouracil and Mitomycin-C) have been used for over three decades with semi-acceptable outcomes. Blebs and bleb associate...
Journal of Current Glaucoma Practice, 2014
Glaucoma filtration surgery is regularly performed for the treat ment 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 anti-fibrotic 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. Vascular endothelial growth factor inhi bition has a role not only in sub conjunctival angiogenesis inhi bition but also it has direct anti-fibrotic properties. Newer phar macological 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.
Drug Design, Development and Therapy, 2014
The purpose of this work was to look into the effects of infliximab on wound healing in experimental glaucoma filtration surgery and to compare the antifibrotic effects of this agent to that of mitomycin-C (MMC). Methods: Twenty-eight male New Zealand White rabbits were randomly assigned to four groups, each including seven rabbits: control group, sham group, MMC group, and infliximab group. The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the MMC treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the infliximab treatment group underwent trabeculectomy and one drop of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery. On day 14 of the experiment, the operated and control eyes were enucleated and histologically and immunohistochemically analyzed. Results: The mean fibroblast and mononuclear cell (MNC) numbers and the mean immunostaining intensities of transforming growth factor-β (TGF-β), fibroblast growth factor-β (FGF-β), and platelet-derived growth factor (PDGF) in the sham group were higher than those of the control group (P,0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-β, FGF-β, and PDGF in the MMC and infliximab groups were statistically significantly lower than those of the sham group (P,0.01). The mean fibroblast and MNC numbers and the mean TGF-β, FGF-β, and PDGF immunostaining intensities of the MMC and infliximab groups were similar (P.0.05). Conclusion: Our study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers and immunostaining intensities of TGF-β, FGF-β, and PDGF.
2013
Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU) injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP) outcome, bleb morphology, postoperative medications, and complications was evaluated. Sign up to receive Clinical Ophthalmology journal here: http://www.dovepress.com/articles.php?article\_id=13416
Investigative Ophthalmology & Visual Science, 2009
PURPOSE. To evaluate the efficacy of bevacizumab as an antifibrotic agent after trabeculectomy in rabbits. METHODS. Forty-two rabbits underwent trabeculectomy and were randomly assigned to receive a postoperative course of seven subconjunctival injections of bevacizumab (1.25 mg, 25 mg/mL), 5-fluorouracil (5-FU; 5 mg, 50 mg/mL), or balanced salt solution (BSS; 0.1 mL, control). Bleb survival and characteristics were evaluated over a 30-day period. The animals were killed on postoperative day (PD)10, PD20, and PD30. Histology and immunohistochemistry of the surgical eyes was performed to evaluate and grade the amount of scarring and fibrosis in each group. RESULTS. Bevacizumab significantly improved the outcome of filtration surgery in this model. Bevacizumab prolonged bleb survival compared with the 5-FU and control groups (16.0 Ϯ 1.3 days vs. 6.9 Ϯ 0.6 and 7.4 Ϯ 0.85 days, respectively; P Ͻ 0.001). Bevacizumab-treated eyes had significantly larger and higher blebs than the control and 5-FU-treated groups (P Ͻ 0.05). Histologic analysis revealed that eyes treated with bevacizumab had significantly less postoperative scarring at the microscopic level at PD10 and PD20 (P ϭ 0.009). CONCLUSIONS. Postoperative subconjunctival injection of bevacizumab is associated with improved trabeculectomy bleb survival in the rabbit model. Bevacizumab may be a useful agent for improving success and limiting scar tissue formation after trabeculectomy.
Wound healing in glaucoma filtering surgery
Survey of Ophthalmology, 1987
Abetract. Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the formation of a filtering bleb. Aqueous in the subconjunctival space may then exit by multiple pathways. Bleb failure most often results from fibroblast proliferation and subconjunctival fibrosis. Factors associated with an increased risk of bleb failure include youth, aphakia, active anterior segment neovascularization, inflammation, previously failed glaucoma filtering surgery, and, possibly, race. Several surgical and pharmacologic techniques have recently been introduced to enhance success in eyes with poor surgical prognoses. To elucidate the scientific rationale of these methods, we summarize the process of wound healing after glaucoma filtering surgery and describe postoperative clinical and histopathologic features, factors which may affect success, and specific methods to improve surgical success.