Journal of Current Glaucoma Practice

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VOLUME 8 , ISSUE 2 ( May-August, 2014 ) > List of Articles

REVIEW ARTICLE

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

Jennifer C Fan Gaskin, Dan Q Nguyen, Ghee Soon Ang, Jeremy O'Connor, Jonathan G Crowston

Keywords : Glaucoma, Wound healing modulation, Filtration surgery

Citation Information : Fan Gaskin JC, Nguyen DQ, Soon Ang G, O'Connor J, Crowston JG. Wound Healing Modulation in Glaucoma Filtration Surgery– Conventional Practices and New Perspectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II). J Curr Glaucoma Pract 2014; 8 (2):46-53.

DOI: 10.5005/jp-journals-10008-1160

License: CC BY-NC 4.0

Published Online: 01-08-2014

Copyright Statement:  Copyright © 2014; Jaypee Brothers Medical Publishers (P) Ltd.


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.


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  1. Cairns JE. Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol 1968 Oct;66(4):673-679.
  2. Spaeth GL. A prospective, controlled study to compare the Scheie procedure with Watson's trabeculectomy. Ophthalmic Surg 1980 Oct;11(10):688-694.
  3. Van Bergen T, Vandewalle E, Van de Veire S, Dewerchin M, Stassen JM, Moons L, Stalmans I. The role of different VEGF isoforms in scar formation after glaucoma filtration surgery. Exp Eye Res 2011 Nov;93(5): 689-699.
  4. Lopilly Park HY, Kim JH, Ahn MD, Park CK. Level of vascular endothelial growth factor in tenon tissue and results of glaucoma surgery. Arch Ophthalmol 2012 Jun;130(6):685-689.
  5. O'Neill EC, Qin Q, Van Bergen NJ, Connell PP, Vasudevan S, Coote MA, Trounce IA, Wong TT, Crowston JG. Antifibrotic activity of bevacizumab on human Tenon's fibroblasts in vitro. Invest Ophthalmol Vis Sci 2010 Dec;51(12):6524-6532.
  6. August DA, Serrano D, Poplin E.” Spontaneous,“delayed colon and rectal anastomotic complications associated with bevacizumab therapy. J Surg Oncol 2008 Feb 1;97(2):180-185.
  7. Coote MA, Ruddle JB, Qin Q, Crowston JG. Vascular changes after intra-bleb injection of bevacizumab. J Glaucoma 2008 Oct-Nov;17(7):517-518.
  8. Nilforushan N, Yadgari M, Kish SK, Nassiri N. Subconjunctival bevacizumab versus mitomycin C adjunctive to trabeculectomy. Am J Ophthalmol 2012 Feb;153(2):352-357.e351.
  9. Sengupta S, Venkatesh R, Ravindran RD. Safety and efficacy of using off-label bevacizumab versus mitomycin C to prevent bleb failure in a single-site phacotrabeculectomy by a randomized controlled clinical trial. J Glaucoma 2012 Sep;21(7):450-459.
  10. Ozgonul C, Mumcuoglu T, Gunal A. The effect of bevacizumab on wound healing modulation in an experimental trabeculectomy model. Curr Eye Res 2014 May;39(5):451-459.
  11. Jurkowska-Dudzinska J, Kosior-Jarecka E, Zarnowski T. Comparison of the use of 5-fluorouracil and bevacizumab in primary trabeculectomy: results at 1 year. Clin Experiment Ophthalmol 2012 May-Jun;40(4):e135-e142.
  12. Simsek T, Cankaya AB, Elgin U. Comparison of needle revision with subconjunctival bevacizumab and 5-fluorouracil injection of failed trabeculectomy blebs. J Ocul Pharmacol Ther 2012 Oct;28(5):542-546.
  13. How A, Chua JL, Charlton A, Su R, Lim M, Kumar RS, Crowston JG, Wong TT. Combined treatment with bevacizumab and 5-fluorouracil attenuates the postoperative scarring response after experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci 2010 Feb;51(2):928-932.
  14. Chua BE, Nguyen DQ, Qin Q, Ruddle JB, Wells AP, Niyadurupola N, Gupta V, Wong TT, Coote MA, Crowston JG. Bleb vascularity following post-trabeculectomy subconjunctival bevacizumab: a pilot study. Clin Experiment Ophthalmol 2012 Nov;40(8): 773-779.
  15. Freiberg FJ, Matlach J, Grehn F, Karl S, Klink T. Postoperative subconjunctival bevacizumab injection as an adjunct to 5-f luorouracil in the management of scarring after trabeculectomy. Clin Ophthalmol 2013;7:1211-1217.
  16. Wilgus TA, Ferreira AM, Oberyszyn TM, Bergdall VK, Dipietro LA. Regulation of scar formation by vascular endothelial growth factor. Lab Invest 2008 Jun;88(6):579-590.
  17. Mello GR, Pizzolatti ML, Wasilewski D, Santhiago MR, Budel V, Moreira H. The effect of subconjunctival bevacizumab on corneal neovascularization, inflammation and re-epithelization in a rabbit model. Clinics (Sau Paulo) 2011;66(8):1443-1450.
  18. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007 Jan;11(1):83-95.
  19. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Oncol 2006 Jan 1;24(1):16-24.
  20. Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, Kozin SV, Petit L, Jain RK, Chung DC, et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 2005 Nov 1;23(31):8136-8139.
  21. Ribatti D. The discovery of the placental growth factor and its role in angiogenesis: a historical review. Angiogenesis 2008; 11(3):215-221.
  22. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 2001 May;7(5):575-583.
  23. Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, et al. Revascularization of ischemic tissues by PlGF treatment and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 2002 Aug;8(8):831-840.
  24. Van Bergen T, Jonckx B, Hollanders K, Sijnave D, Van de Velde S, Vandewalle E, Moons L, Stassen JM, Stalmans I. Inhibition of placental growth factor improves surgical outcome of glaucoma surgery. J Cell Mol Med 2013 Dec;17(12):1632-1643.
  25. Ebert EC. Infliximab and the TNF-alpha system. Am J Physiol Gastrointest Liver Physiol 2009 Mar;296(3):612G-620G.
  26. Hosseini H, Safaei A, Khalili MR, Nowroozizadeh B, Eghtedari M, Farvardin M, Nowroozizadeh S, Tolide-Ie HR. Intravitreal infliximab in experimental endotoxin-induced uveitis. Eur J Ophthalmol 2009 Sep-Oct;19(5):818-823.
  27. Demir T, Gödekmerdan A, Balbaba M, Türkçüoglu P, Ilhan F, Demir N. The effect of infliximab, cyclosporine A and recombinant IL-10 on vitreous cytokine levels in experimental autoimmune uveitis. Indian J Ophthalmol 2006 Dec;54(4):241-245.
  28. Turgut B, Eren K, Akin MM, Demir T, Kobat S. Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery. Drug Des Devel Ther 2014 May 2;8:421-429.
  29. Turgut B, Eren K, Akin MM, Bilir Can N, Demir T. Impact of trastuzumab on wound healing in experimental glaucoma surgery. Clin Experiment Ophthalmol 2014 May 7.
  30. Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol 2007 Jun;18(6):977-984.
  31. Evans WH, De Vuyst E, Leybaert L. The gap junction cellular internet: connexin hemichannels enter the signalling limelight. Biochem J 2006 Jul 1;397(1):1-14.
  32. Beyer EC, Steinberg TH. Evidence that the gap junction protein connexin-43 is the ATP-induced pore of mouse macrophages. J Biol Chem 1991 May 5;266(13):7971-7974.
  33. Oviedo-Orta E, Errington RJ, Evans WH. Gap junction intercellular communication during lymphocyte transendothelial migration. Cell Biol Int 2002;26(3):253-263.
  34. Ehrlich HP, Gabbiani G, Meda P. Cell coupling modulates the contraction of fibroblast-populated collagen lattices. J Cell Physiol 2000 Jul;184(1):86-92.
  35. Goodenough DA, Goliger JA, Paul DL. Connexins, connexons and intercellular communication. Annu Rev Biochem 1996;65:475-502.
  36. Kumar NM, Gilula NB. The gap junction communication channel. Cell 1996 Feb 9;84(3):381-388.
  37. Coutinho P, Qiu C, Frank S, Wang CM, Brown T, Green CR, Becker DL. Limiting burn extension by transient inhibition of Connexin43 expression at the site of injury. Br J Plast Surg 2005 Jul;58(5):658-667.
  38. Qiu C, Coutinho P, Frank S, Franke S, Law LY, Martin P, Green CR, Becker DL. Targeting connexin43 expression accelerates the rate of wound repair. Curr Biol 2003 Sep 30;13(19):1697-1703.
  39. Deva NC, Zhang J, Green CR, Danesh-Meyer HV. Connexin43 modulation inhibits scarring in a rabbit eye glaucoma trabeculectomy model. Inflammation 2012 Aug;35(4):1276-1286.
  40. Fujishima H, Shimazaki J, Shinozaki N, Tsubota K. Trabeculectomy with the use of amniotic membrane for uncontrollable glaucoma. Ophthalmic Surg Lasers 1998 May;29(5):428-431.
  41. Drolsum L, Willoch C, Nicolaissen B. Use of amniotic membrane as an adjuvant in refractory glaucoma. Acta Ophthalmol Scand 2006 Dec;84(6):786-789.
  42. Sheha H, Kheirkhah A, Taha H. Amniotic membrane transplantation in trabeculectomy with mitomycin C for refractory glaucoma. J Glaucoma 2008 Jun-Jul;17(4):303-307.
  43. Bruno CA, Eisengart JA, Radenbaugh PA, Moroi SE. Subconjunctival placement of human amniotic membrane during high risk glaucoma filtration surgery. Ophthalmic Surg Lasers Imaging 2006 May-Jun;37(3):190-197.
  44. Eliezer RN, Kasahara N, Caixeta-Umbelino C, Pinheiro RK, Mandia C Jr, Malta RF. Use of amniotic membrane in trabeculectomy for the treatment of glaucoma: a pilot study. Arq Bras Oftalmol 2006 May-Jun;69(3):309-312.
  45. Stavrakas P, Georgopoulos G, Milia M, Papaconstantinou D, Bafa M, Stavrakas E, Moschos M. The use of amniotic membrane in trabeculectomy for the treatment of primary open-angle glaucoma: a prospective study. Clin Ophthalmol 2012;6:205-212.
  46. Nakamura M, Naka M, Tatsumi Y, Nagai-Kusuhara A, Kanamori A, Yamada Y, Negi A. Filtering bleb structure associated with long-term intraocular pressure control after amniotic membrane-assisted trabeculectomy. Curr Eye Res 2012 Mar;37(3):239-250.
  47. Kim C, Kim Y, Choi S, Lee S, Ahn B. Clinical experience of e-PTFE membrane implant surgery for refractory glaucoma. Br J Ophthalmol 2003 Jan;87(1):63-70.
  48. Choi YJ, Kim CS, Ahn BH. A comparison of the clinical effect between e-PTFE membrane-tube implant and Ahmed glaucoma valve implant for the treatment of refractory glaucoma. Korean J Ophthalmol 2003 Dec;17(2):106-113.
  49. DeCroos FC, Ahmad S, Kondo Y, Chow J, Mordes D, Lee MR, Asrani S, Allingham RR, Olbrich KC, Klitzman B. Expanded polytetrafluoroethylene membrane alters tissue response to implanted Ahmed glaucoma valve. Curr Eye Res 2009 Jul;34(7): 562-567.
  50. Cillino S, Zeppa L, Di Pace F, Casuccio A, Morreale D, Bocchetta F, Lodato G. E-PTFE (Gore-Tex) implant with or without low-dosage mitomycin-C as an adjuvant in penetrating glaucoma surgery: 2 year randomized clinical trials. Acta Ophthalmol 2008 May;86(3):314-321.
  51. Takeuchi K, Nakazawa M, Yamazaki H, Miyagawa Y, Ito T, Ishikawa F, Metoki T. Solid hyaluronic acid film and the prevention of postoperative fibrous scar formation in experimental animal eyes. Arch Ophthalmol 2009 Apr;127(4):460-464.
  52. Tsurumaru N, Arai M, Teruya K, Sueda J, Yamakawa R. Seprafilm as a new antifibrotic agent following trabeculectomy in rabbit eyes. Jpn J Ophthalmol 2009 Mar;53(2):164-170.
  53. Akyol N, Aydogan S, Akpolat N. Effects of membrane adhesion barriers on wound healing reaction after glaucoma filtration surgery: a comparative study with Interceed and Seprafilm. Eur J Ophthalmol 2005 Sep-Oct;15(5):591-597.
  54. Akyol N, Akpolat N. Effects of intraoperative oxidated regenerated cellulose on wound healing reaction after glaucoma filtration surgery: a comparative study with Interceed and Surgicel. Indian J Ophthalmol 2008 Mar-Apr;56(2):109-114.
  55. Okuda T, Higashide T, Fukuhira Y, Sumi Y, Shimomura M, Sugiyama K. A thin honeycomb-patterned film as an adhesion barrier in an animal model of glaucoma filtration surgery. J Glaucoma 2009 Mar;18(3):220-226.
  56. Hsu WC, Ritch R, Krupin T, Chen HS. Tissue bioengineering for surgical bleb defects: an animal study. Graefes Arch Clin Exp Ophthalmol 2008 May;246(5):709-717.
  57. Cillino S, Di Pace F, Cillino G, Casuccio A. Biodegradable collagen matrix implant vs mitomycin-C as an adjuvant in trabeculectomy: a 24-month, randomized clinical trial. Eye (Lond) 2011 Dec;25(12):1598-1606.
  58. Papaconstantinou D, Georgalas I, Karmiris E, Diagourtas A, Koutsandrea C, Ladas I, Apostolopoulos M, Georgopoulos G. Trabeculectomy with OloGen versus trabeculectomy for the treatment of glaucoma: a pilot study. Acta Ophthalmol 2010 Feb; 88(1):80-85.
  59. Senthil S, Rao HL, Babu JG, Mandal AK, Garudadri CS. Comparison of outcomes of trabeculectomy with mitomycin C vs. ologen implant in primary glaucoma. Indian J Ophthalmol 2013 Jul;61(7):338-342.
  60. Rosentreter A, Schild AM, Jordan JF, Krieglstein GK, Dietlein TS. A prospective randomised trial of trabeculectomy using mitomycin C vs an ologen implant in open angle glaucoma. Eye (Lond) 2010 Sep;24(9):1449-1457.
  61. Narayanaswamy A, Perera SA, Htoon HM, Hoh ST, Seah SK, Wong TT, Aung T. Efficacy and safety of collagen matrix implants in phacotrabeculectomy and comparison with mitomycin C augmented phacotrabeculectomy at 1 year. Clin Experiment Ophthalmol 2013 Aug;41(6):552-560.
  62. Johnson MS, Sarkisian SR Jr. Using a collagen matrix implant (Ologen) versus mitomycin-C as a wound healing modulator in trabeculectomy with the Ex-PRESS mini glaucoma device: a 12-month retrospective review. J Glaucoma 2014 Dec;23(9):649-652.
  63. Dietlein TS, Lappas A, Rosentreter A. Secondary subconjunctival implantation of a biodegradable collagen-glycosaminoglycan matrix to treat ocular hypotony following trabeculectomy with mitomycin C. Br J Ophthalmol 2013 Aug;97(8):985-988.
  64. Koz OG, Ozhuy S, Tezel GG, Karaman N, Unlu N, Yarangumeli A, Kural G. The effect of paclitaxel on conjunctival wound healing: a pilot study. J Glaucoma 2007 Oct-Nov;16(7):610-615.
  65. Kojima S, Sugiyama T, Takai S, Jin D, Shibata M, Oku H, Tabata Y, Ikeda T. Effects of gelatin hydrogel containing chymase inhibitor on scarring in a canine filtration surgery model. Invest Ophthalmol Vis Sci 2011 Sep 29;52(10):7672-7680.
  66. Liang L, Xu XD, Zhang XZ, Feng M, Peng C, Jiang FG. Prevention of filtering surgery failure by subconjunctival injection of a novel peptide hydrogel into rabbit eyes. Biomed Mater 2010 Aug;5(4):045008.
  67. Xu XD, Liang L, Chen CS, Lu B, Wang NL, Jiang FG, Zhang XZ, Zhuo RX. Peptide hydrogel as an intraocular drug delivery system for inhibition of postoperative scarring formation. ACS Appl Mater Interfaces 2010 Sep;2(9):2663-2671.
  68. Paula JS, Ribeiro VR, Chahud F, Cannellini R, Monteiro TC, Gomes EC, Reinach PS, Rodrigues Mde L, Silva-Cunha A. Bevacizumab-loaded polyurethane subconjunctival implants: effects on experimental glaucoma filtration surgery. J Ocul Pharmacol Ther 2013 Jul-Aug;29(6):566-573.
  69. Spitzer MS, Yoeruek E, Kaczmarek RT, Sierra A, Aisenbrey S, Grisanti S, Bartz-Schmidt KU, Szurman P. Sodium hyaluronate gels as a drug-release system for corticosteroids: release kinetics and antiproliferative potential for glaucoma surgery. Acta Ophthalmol 2008 Dec;86(8):842-848.
  70. Lopes JF, Moster MR, Wilson RP, Altangerel U, Alvim HS, Tong MG, Fontanarosa J, Steinmann WC. Subconjunctival sodium hyaluronate 2.3% in trabeculectomy: a prospective randomized clinical trial. Ophthalmology 2006 May;113(5):756-760.
  71. Narayanaswamy AK, Lee K, Zhen M, Chua J, Chai SM, Boey PY, Zheng C, Aung T, Venkatraman S, Wong TT. Randomized, controlled trial of a sustained delivery formulation of 5-fluo rouracil for the treatment of failing blebs. Ophthalmology 2012 Feb;119(2):314-320.
  72. Shafi F, Agrawal P, Holder R, Sung V. Bleb needling with subconjunctival injection of sodium hyaluronate 1.4%: 1-year outcomes. Can J Ophthalmol 2011 Dec;46(6):537-542.
  73. Ang M, Yan P, Zhen M, Foo S, Venkatraman SS, Wong TT. Evaluation of sustained release of PLC-loaded prednisolone acetate microfilm on postoperative inflammation in an experimental model of glaucoma filtration surgery. Curr Eye Res 2011 Dec;36(12):1123-1128.
  74. Yan ZC, Bai YJ, Tian Z, Hu HY, You XH, Lin JX, Liu SR, Zhuo YH, Luo RJ. Anti-proliferation effects of Sirolimussustained delivery film in rabbit glaucoma filtration surgery. Mol Vis 2011;17:2495-2506.
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