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Overview of cicatricial modulators in glaucoma fistulizing surgery

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Abstract

Introduction

Trabeculectomy is the most commonly performed surgery for the definitive treatment of glaucoma. Despite its high resolvability, the postoperative period requires high caution so that excessive filtration or scarring does not occur. This paper aimed to research alternative options to those most used as healing modulators, mitomycin C (MMC) and 5-fluorouracil, commonly associated with complications.

Methods

This systematic review used the PubMed and SciELO databases, covering publications from 1972 to 2019.

Results

A total of 31 substances and methods were analyzed.

Conclusion

Some, such as anti-VEGF, glucocorticoids and betatherapy, did not show results statistically superior to those of MMC. Others, such as the enzyme α5β1-integrin and Ologen®, demonstrated efficacy and safety at least similar to that of this drug. In conclusion, further research is still needed for drugs that lead to the same results as mitomycin, but with fewer side effects. More recent studies have focused on technologies that increase communication between target tissues and antifibrotic molecules at the cellular level, being a promising bet for the future.

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References

  1. Cordeiro MF, Chang L, Lim KS et al (2000) Modulating conjunctival wound healing. Eye (Lond) 14(Pt 3B):536–547

    Google Scholar 

  2. Khaw PT, Chang L, Wong TT et al (2001) Modulation of wound healing after glaucoma surgery. Curr Opin Ophthalmol 12(2):143–148

    CAS  PubMed  Google Scholar 

  3. Shapiro MS, Thoft RA, Friend J et al (1985) 5-Fluorouracil toxicity to the ocular surface epithelium. Invest Ophthalmol Vis Sci 26(4):580–583

    CAS  PubMed  Google Scholar 

  4. Nuyts RM, Felten PC, Pels E et al (1994) Histopathologic effects of mitomycin C after trabeculectomy in human glaucomatous eyes with persistent hypotony. Am J Ophthalmol 118(2):225–237

    CAS  PubMed  Google Scholar 

  5. Costa VP, Vasconcellos JP, Comegno PEC et al (1999) O uso da mitomicina C em cirurgia combinada. Arq Bras Oftalmol 62(5):577–580

    Google Scholar 

  6. Vahedian Z, Mafi M, Fakhraie G et al (2017) Short-term results of trabeculectomy using adjunctive intracameral bevacizumab: a randomized controlled trial. J Glaucoma 26(9):829–834

    PubMed  Google Scholar 

  7. Zhang F, Liu K, Cao M et al (2019) Rosiglitazone treatment prevents postoperative fibrosis in a rabbit model of glaucoma filtration surgery. Invest Ophthalmol Vis Sci 60(7):2743–2752

    CAS  PubMed  Google Scholar 

  8. Pitha I, Oglesby E, Chow A et al (2018) Rho-kinase inhibition reduces myofibroblast differentiation and proliferation of scleral fibroblasts induced by transforming growth factor β and experimental glaucoma. Transl Vis Sci Technol 7(6):6

    PubMed  PubMed Central  Google Scholar 

  9. Park J, Yoo C, Kim YY (2016) Effect of lovastatin on wound-healing modulation after glaucoma filtration surgery in a rabbit model. Invest Ophthalmol Vis Sci 57(4):1871–1877

    CAS  PubMed  Google Scholar 

  10. Shi H, Wang H, Fu S et al (2017) Losartan attenuates scar formation in filtering bleb after trabeculectomy. Invest Ophthalmol Vis Sci 58(3):1478–1486

    CAS  PubMed  Google Scholar 

  11. Gressel MG, Parrish RK 2nd, Folberg R (1984) 5-fluorouracil and glaucoma filtering surgery: I. An animal model. Ophthalmology 91(4):378–383

    CAS  PubMed  Google Scholar 

  12. FFSSG (1989) Fluorouracil filtering surgery study one-year follow-up. The Fluorouracil Filtering Surgery Study Group. Am J Ophthalmol 108(6):625–635

    Google Scholar 

  13. FFSSG (1996) Five-year follow-up of the Fluorouracil Filtering Surgery Study. The Fluorouracil Filtering Surgery Study Group. Am J Ophthalmol 121:349–366

    Google Scholar 

  14. Khaw PT, Sherwood MB, MacKay SL et al (1992) Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon’s capsule fibroblasts. Arch Ophthalmol 110(8):1150–1154

    CAS  PubMed  Google Scholar 

  15. Cordeiro MF, Constable PH, Alexander RA et al (1997) Effect of Varying the mitomycin-C treatment area in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci 38(8):1639–1646

    CAS  PubMed  Google Scholar 

  16. Mégevand GS, Salmon JF, Scholtz RP et al (1995) The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery. Ophthalmology 102(1):84–90

    PubMed  Google Scholar 

  17. Schnyder CC, Bernasconi O, Mermoud A et al (1995) Comparative study of administration time of mitomycin C in trabeculectomy: 2.5 or 5 minutes? Klin Monbl Augenheilkd 206(5):307–311

    CAS  PubMed  Google Scholar 

  18. Nguyen KD, Lee DA (1992) Effect of steroids and nonsteroidal antiinflammatory agents on human ocular fibroblast. Invest Ophthalmol Vis Sci 33(9):2693–2701

    CAS  PubMed  Google Scholar 

  19. Nguyen KD, Lee DA (1993) In vitro evaluation of antiproliferative potential of topical cyclooxygenase inhibitors in human Tenon’s fibroblasts. Exp Eye Res 57(1):97–105

    CAS  PubMed  Google Scholar 

  20. Armstrong JJ, Denstedt JT, Trelford CB et al (2019) Differential effects of dexamethasone and indomethacin on Tenon’s capsule fibroblasts: implications for glaucoma surgery. Exp Eye Res 182:65–73

    CAS  PubMed  Google Scholar 

  21. Chihara E, Dong J, Ochiai H et al (2002) Effects of tranilast on filtering blebs: a pilot study. J Glaucoma 11(2):127–133

    PubMed  Google Scholar 

  22. Wong TT, Mead AL, Khaw PT (2005) Prolonged antiscarring effects of ilomastat and MMC after experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci 46(6):2018–2022

    PubMed  Google Scholar 

  23. CAT-152 0102 Trabeculectomy Study Group, Khaw P, Grehn F et al (2007) A phase III study of subconjunctival human anti-transforming growth factor beta(2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmology 114(10):1822–1830

    Google Scholar 

  24. Sapitro J, Dunmire JJ, Scott SE et al (2010) Suppression of transforming growth factor-β effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor. Mol Vis 16:1880–1892

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Jampel HD, Moon JI (1998) The effect of paclitaxel powder on glaucoma filtration surgery in rabbits. J Glaucoma 7(3):170–177

    CAS  PubMed  Google Scholar 

  26. Choritz L, Grub J, Wegner M et al (2010) Paclitaxel inhibits growth, migration and collagen production of human Tenon’s fibroblasts–potential use in drug-eluting glaucoma drainage devices. Graefes Arch Clin Exp Ophthalmol 248(2):197–206

    CAS  PubMed  Google Scholar 

  27. Khaw PT, Ward S, Grierson I et al (1991) Effect of beta radiation on proliferating human Tenon’s capsule fibroblasts. Br J Ophthalmol 75(10):580–583

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Rehman SU, Amoaku WM, Doran RM et al (2002) Randomized controlled clinical trial of beta irradiation as an adjunct to trabeculectomy in open-angle glaucoma. Ophthalmology 109(2):302–306

    PubMed  Google Scholar 

  29. Kirwan JF, Cousens S, Venter L et al (2006) Effect of beta radiation on success of glaucoma drainage surgery in South Africa: randomised controlled trial. BMJ 333(7575):942

    PubMed  PubMed Central  Google Scholar 

  30. Fendi LI, Arruda GV, Costa VP et al (2011) Meta-analysis of beta radiation augmentation for trabeculectomy—results in distinct ethnic groups. Arq Bras Oftalmol 74(4):300–305

    PubMed  Google Scholar 

  31. Zhong Y, Zhou Y, Wang K (2000) Effect of Amniotic Membrane on Filtering Bleb After Trabeculectomy in Rabbit Eyes. Yan Ke Xue Bao 16(2):73–83

    CAS  PubMed  Google Scholar 

  32. Barton K, Budenz DL, Khaw PT et al (2001) Glaucoma filtration surgery using amniotic membrane transplantation. Invest Ophthalmol Vis Sci 42(8):1762–1768

    CAS  PubMed  Google Scholar 

  33. Wang L, Liu X, Zhang P et al (2005) An experimental trial of glaucoma filtering surgery with amniotic membrane. Yan Ke Xue Bao 21(2):126–131

    CAS  PubMed  Google Scholar 

  34. Eliezer RN, Kasahara N, Caixeta-Umbelino C et al (2006) Use of amniotic membrane in trabeculectomy for the treatment of glaucoma: a pilot study. Arq Bras Oftalmol 69(3):309–312

    PubMed  Google Scholar 

  35. Stavrakas P, Georgopoulos G, Milia M et al (2012) The use of amniotic membrane in trabeculectomy for the treatment of primary open-angle glaucoma: a prospective study. Clin Ophthalmol 6:205–212

    PubMed  PubMed Central  Google Scholar 

  36. Yadava U, Jaisingh K, Dangda S et al (2017) Simultaneous use of amniotic membrane and mitomycin C in trabeculectomy for primary glaucoma. Indian J Ophthalmol 65(11):1151–1155

    PubMed  PubMed Central  Google Scholar 

  37. Wang F, Qi LX, Su Y et al (2010) Inhibition of cell proliferation of Tenon’s capsule fibroblast by Sphase kinase-interacting protein 2 targeting SiRNA through increasing p27 protein level. Invest Ophthalmol Vis Sci 51(3):1475–1482

    PubMed  Google Scholar 

  38. Zhong H, Sun G, Lin X et al (2011) Evaluation of pirfenidone as a new postoperative antiscarring agent in experimental glaucoma surgery. Invest Ophthalmol Vis Sci 52(6):3136–3142

    CAS  PubMed  Google Scholar 

  39. Wang W, Zhang J, Huang Y et al (2011) Clinical study on interferon treatment of early scarring in filtering bleb. Eye Sci 26(4):197–200

    CAS  PubMed  Google Scholar 

  40. Ang M, Yan P, Zhen M et al (2011) Evaluation of sustained release of PLC-loaded prednisolone acetate microfilm on postoperative inflammation in an experimental model of glaucoma filtration surgery. Curr Eye Res 36(12):1123–1128

    CAS  PubMed  Google Scholar 

  41. SooHoo JR, Seibold LK, Laing AE et al (2012) Bleb morphology and histology in a rabbit model of glaucoma filtration surgery using Ozurdex® or mitomycin-C. Mol Vis 18:714–719

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Arslan S, Aydemir O, Güler M et al (2012) Modulation of postoperative scarring with tacrolimus and octreotide in experimental glaucoma filtration surgery. Curr Eye Res 37(3):228–233

    CAS  PubMed  Google Scholar 

  43. Min J, Lukowski ZL, Levine MA et al (2012) Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model. PLoS ONE 7(4):e35627

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lukowski ZL, Min J, Beattie AR et al (2013) Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model. J Glaucoma 22(2):145–151

    PubMed  PubMed Central  Google Scholar 

  45. Memarzadeh F, Varma R, Lin LT et al (2009) Postoperative use of bevacizumab as an antifibrotic agent in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci 50(7):3233–3237

    PubMed  Google Scholar 

  46. Paula JS, Ribeiro VRC, Chahud F et al (2013) Bevacizumab-loaded polyurethane subconjunctival implants: effects on experimental glaucoma filtration surgery. J Ocul Pharmacol Ther 29(6):566–573

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Ozgonul C, Mumcuoglu T, Gunal A (2014) The effect of bevacizumab on wound healing modulation in an experimental trabeculectomy model. Curr Eye Res 39(5):451–459

    CAS  PubMed  Google Scholar 

  48. Cheng G, Xiang H, Yang G et al (2015) Direct effects of bevacizumab on rat conjunctival fibroblast. Cell Biochem Biophys 73(1):45–50

    CAS  PubMed  Google Scholar 

  49. Li Z, Van Bergen T, Van de Veire S et al (2009) Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery. Invest Ophthalmol Vis Sci 50(11):5217–5225

    PubMed  Google Scholar 

  50. Liu X, Du L, Li N (2016) The effects of bevacizumab in augmenting trabeculectomy for glaucoma: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 95(15):e3223

    CAS  Google Scholar 

  51. Chen HJ, Lin C, Lee CH et al (2018) Efficacy and safety of bevacizumab combined with mitomycin C or 5-fluorouracil in primary trabeculectomy: a meta-analysis of randomized clinical trials. Ophthalmic Res 59(3):155–163

    CAS  PubMed  Google Scholar 

  52. Akkan JU, Cilsim S (2015) Role of subconjunctival bevacizumab as an adjuvant to primary trabeculectomy: a prospective randomized comparative 1-year follow-up study. J Glaucoma 24(1):1–8

    PubMed  Google Scholar 

  53. Noh SM, Abdul Kadir SH, Crowston JG et al (2015) Effects of ranibizumab on TGF-β1 and TGF-β2 production by human Tenon’s fibroblasts: an in vitro study. Mol Vis 21:1191–1200

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Pro MJ, Freidl KB, Neylan CJ et al (2015) Ranibizumab versus mitomycin C in primary trabeculectomy—a pilot study. Curr Eye Res 40(5):510–515

    CAS  PubMed  Google Scholar 

  55. Turgut B, Eren K, Akin MM et al (2014) Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery. Drug Des Devel Ther 8:421–429

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Chen YH, Liang CM, Chen CL et al (2013) Silibinin inhibits myofibroblast transdifferentiation in human tenon fibroblasts and reduces fibrosis in a rabbit trabeculectomy model. Acta Ophthalmol 91(7):e506–e515

    CAS  PubMed  Google Scholar 

  57. Ferreira JL, Chahud F, Ramalho LN et al (2015) Rosmarinic Acid Suppresses Subconjunctival Neovascularization In Experimental Glaucoma Surgery. Curr Eye Res 40(11):1134–1140

    CAS  Google Scholar 

  58. Turgut B, Eren K, Akin MM et al (2015) Impact of trastuzumab on wound healing in experimental glaucoma surgery. Clin Experiment Ophthalmol 43(1):67–76

    PubMed  Google Scholar 

  59. Meyer-Ter-Vehn T, Katzenberger B, Han H et al (2008) Lovastatin inhibits TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts. Invest Ophthalmol Vis Sci 49(9):3955–3960

    PubMed  Google Scholar 

  60. Johnson MS, Sarkisian SR Jr (2014) 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 23(9):649–652

    PubMed  Google Scholar 

  61. Ji Q, Qi B, Liu L et al (2015) Efficacy and safety of ologen implant versus mitomycin C in primary trabeculectomy: a meta-analysis of randomized clinical trials. J Glaucoma 24(5):e88–e94

    PubMed  Google Scholar 

  62. Cillino S, Casuccio A, Pace FD et al (2016) Biodegradable collagen matrix implant versus mitomycin-C in trabeculectomy: five-year follow-up. BMC ophthalmol 16:24

    PubMed  PubMed Central  Google Scholar 

  63. Van Bergen T, Zahn G, Caldirola P et al (2016) The α5β1 integrin inhibition by CLT-28643 reduces post-operative wound healing in a mouse model of glaucoma filtration surgery. Invest Ophthalmol Vis Sci 57(14):6428–6439

    PubMed  Google Scholar 

  64. Schultheiss M, Schnichels S, Konrad EM et al (2017) α5β1-Integrin inhibitor (CLT-28643) effective in rabbit trabeculectomy model. Acta Ophthalmol 95(1):e1–e9

    CAS  PubMed  Google Scholar 

  65. Sharma A, Anumanthan G, Reyes M et al (2016) Epigenetic modification prevents excessive wound healing and scar formation after glaucoma filtration surgery. Invest Ophthalmol Vis Sci 57(7):3381–3389

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Yang J, Shi LK, Sun HM et al (2017) Antiproliferative effect of double suicide gene delivery mediated by polyamidoamine dendrimers in human Tenon’s capsule fibroblasts. Exp Ther Med 14(6):5473–5479

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Honjo M, Tanihara H, Kameda T et al (2007) Potential role of Rho-associated protein kinase inhibitor Y-27632 in glaucoma filtration surgery. Invest Ophthalmol Vis Sci 48(12):5549–5557

    PubMed  Google Scholar 

  68. Van de Velde S, Van Bergen T, Vandewalle E et al (2015) Rho kinase inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery. Prog Brain Res 220:283–297

    PubMed  Google Scholar 

  69. Lin X, Wen J, Liu R et al (2018) Nintedanib inhibits TGF-β-induced myofibroblast transdifferentiation in human Tenon’s fibroblasts. Mol Vis 24:789–800

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Cairns JE (1968) Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol 66:673–679

    CAS  PubMed  Google Scholar 

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  1. Faculdade de Medicina, Unichristus, Fortaleza, Ceará, Brazil

    Camille Moura de Oliveira & Juliana de Lucena Martins Ferreira

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  1. Camille Moura de Oliveira
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  2. Juliana de Lucena Martins Ferreira
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Correspondence to Camille Moura de Oliveira.

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de Oliveira, C.M., Ferreira, J.L.M. Overview of cicatricial modulators in glaucoma fistulizing surgery. Int Ophthalmol 40, 2789–2796 (2020). https://doi.org/10.1007/s10792-020-01454-w

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