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      Wound Healing Modulation in Glaucoma Filtration Surgery–Conventional Practices and New Perspectives: The Role of Antifibrotic Agents (Part I)

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          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 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.

          How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glaucoma Filtration Surgery–Conventional Practices and New Pers pectives: The Role of Antifibrotic Agents (Part I). J Curr Glaucoma Pract 2014;8(2):37-45.

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          Trabeculectomy in the 21st century: a multicenter analysis.

          To evaluate the efficacy and safety of current trabeculectomy surgery in the United Kingdom. Cross-sectional, multicenter, retrospective follow-up. A total of 428 eyes of 395 patients. Consecutive trabeculectomy cases with open-angle glaucoma and no previous incisional glaucoma surgery from 9 glaucoma units were evaluated retrospectively. Follow-up was a minimum of 2 years. Surgical success, intraocular pressure (IOP), visual acuity, complications, and interventions. Success was stratified according to IOP, use of hypotensive medications, bleb needling, and resuturing/revision for hypotony. Reoperation for glaucoma and loss of perception of light were classified as failures. Antifibrotics were used in 400 cases (93%): mitomycin C (MMC) in 271 (63%), 5-fluorouracil (5-FU) in 129 (30%), and no antifibrotic in 28 (7%). At 2 years, IOP (mean ± standard deviation) was 12.4 ± 4 mmHg, and 342 patients (80%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP without IOP-lowering medication, whereas 374 patients (87%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP overall. An IOP ≤18 mmHg and 20% reduction of preoperative IOP were achieved by 337 trabeculectomies (78%) without IOP-lowering treatment and by 367 trabeculectomies (86%) including hypotensive medication. Postoperative treatments included suture manipulation in 184 patients (43%), resuturing or revision for hypotony in 30 patients (7%), bleb needling in 71 patients (17%), and cataract extraction in 111 of 363 patients (31%). Subconjunctival 5-FU injection was performed postoperatively in 119 patients (28%). Visual loss of >2 Snellen lines occurred in 24 of 428 patients (5.6%). A total of 31 of the 428 patients (7.2%) had late-onset hypotony (IOP 2 Snellen lines. Bleb leaks were observed in 59 cases (14%), 56 (95%) of which occurred within 3 months. Two patients developed blebitis. Bleb-related endophthalmitis developed in 1 patient within 1 month postoperatively and in 1 patient at 3 years. There was an endophthalmitis associated with subsequent cataract surgery. This survey shows that good trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive postoperative care is required. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            Wound healing in glaucoma filtering surgery.

            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.
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              Endophthalmitis after filtering surgery with mitomycin.

              To identify the incidence, causative organisms, and clinical outcomes of eyes with bleb-associated endophthalmitis after glaucoma filtering procedures with adjunctive mitomycin. Retrospective analysis of 773 consecutive eyes that underwent glaucoma filtering surgery at the Bascom Palmer Eye Institute, Miami, Fla. The course of 609 eyes from 485 patients with a minimum of 3 months of follow-up were reviewed. Mean follow-up was 16.0 +/- 11.5 months (range, 3-48 months). Of the 609 eyes, 13 (2.1%) developed bleb-associated endophthalmitis an average of 18.5 +/- 13.2 months after surgery (range, 1-45 months). The incidence of bleb-associated endophthalmitis was significantly greater after inferior trabeculectomy (7.8% per patient-year) than after superior trabeculectomy (1.3% per patient-year) by Kaplan-Meier estimates (P = .02, log rank test). The cumulative incidence was 13% for inferior limbal blebs and 1.6% for superior limbal blebs. Nine (69.2%) of the 13 eyes were culture positive. Streptococcus sanguis and Haemophilus influenzae (6/13 [46.2%]) were the most frequent causative organisms. The mean increase in intraocular pressure after endophthalmitis treatment was 1.2 mm Hg, with a mean decrease in visual acuity of 1.42 logMAR units. Eight (61.5%) of the 13 eyes had a final acuity of 20/400 or better. The incidence of bleb-associated endophthalmitis after guarded filtering surgery performed with adjunctive mitomycin is higher than the reported rate in eyes undergoing filtering surgery without the use of antifibrotic agents (0.2%-1.5%). Inferior limbal trabeculectomy carries the highest risk of infection. Eyes with mitomycin blebs maintained excellent filtration capacity. However, after treatment of the infection, the visual outcomes were generally poor.
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                Author and article information

                Contributors
                Journal
                J Curr Glaucoma Pract
                J Curr Glaucoma Pract
                JOCGP
                Journal of Current Glaucoma Practice
                Jaypee Brothers Medical Publishers
                0974-0333
                0975-1947
                May-Aug 2014
                12 June 2014
                : 8
                : 2
                : 37-45
                Affiliations
                Glaucoma Fellow, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Australia
                Consultant, Department of Ophthalmology, Mid Cheshire Hospitals, NHS Foundation Trust, Cheshire; Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire, UK
                Consultant, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Australia
                Consultant, Glaucoma Investigation and Research Unit, University Hospital Limerick, Ireland
                Pofessor, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Australia
                Author notes
                Jennifer C Fan Gaskin, Glaucoma Fellow, Glaucoma Investigation and Research Unit, Centre for Eye Research, University of Melbourne, Melbourne, Victoria, Australia Phone: 0061406494994, e-mail: drjfan@gmail.com
                Article
                10.5005/jp-journals-10008-1159
                4741165
                26997807
                d500261a-4ecf-4264-86ac-3dff0cca0723
                Copyright © 2014; Jaypee Brothers Medical Publishers (P) Ltd.

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                : 09 January 2014
                : 27 March 2014
                Categories
                Review Article

                glaucoma,trabeculectomy,filtration surgery,antimetabolites,wound healing modulation,scarring.

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