Inflammation and glaucoma filtration surgery. Part 1: risk factors for surgical failure

Intraocular pressure (IOP) is the only modifiable risk factor for the development and progression of glaucomatous optic neuropathy, making its reduction the primary goal of glaucoma therapy. Despite advances in medical and laser treatment, filtering surgery remains a key (and often the only) method of IOP control. However, in patients with a long history of glaucoma, chronic exposure to topical hypotensive medications, particularly preservative-containing formulations, induces a spectrum of pathological ocular surface alterations characterized predominantly by inflammation. These pathological changes are characterized by the activation of inflammatory mediators and cellular infiltration of the ocular surface tissues, which significantly impairs postoperative wound healing and ultimately determines surgical outcomes. A comprehensive understanding of the pathophysiological mechanisms underlying these changes provides the foundation for developing targeted preventive and therapeutic strategies aimed at improving long-term surgical success. This review evaluates current evidence regarding the consequences of long-term hypotensive therapy on the ocular surface, with particular emphasis on differential assessment of the effects of active ingredients and preservatives in eye drops, the impact of previous ophthalmic surgeries, and the pro-inflammatory effects associated with recent glaucoma filtration surgery

1. Ruiz-Lozano RE, Azar NS, Mousa HM, et al. Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy. Front Toxicol 2023; 5:1067942. https://doi.org/10.3389/ftox.2023.1067942

2. Zhang X, Vadoothker S, Munir WM, Saeedi O. Ocular Surface Disease and Glaucoma Medications: A Clinical Approach. Eye Contact Lens 2019; 45(1):11-18. https://doi.org/10.1097/ICL.0000000000000544

3. Baudouin C, Renard JP, Nordmann JP, et al. Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. Eur J Ophthalmol Published online June 11, 2012. https://doi.org/10.5301/ejo.5000181

4. Аntonova АV, Nikolaenko VP, Brzheskiy VV, Vuks AJ. Changes in the oculas surface after hypotensive surgery. Ophthalmology Reports 2023; 16(1):47-58. https://doi.org/10.17816/OV321181

5. Baudouin C, Liang H, Hamard P, et al. The ocular surface of glaucoma patients treated over the long term expresses inflammatory markers related to both T-helper 1 and T-helper 2 pathways. Ophthalmology 2008; 115(1):109-115. https://doi.org/10.1016/j.ophtha.2007.01.036

6. Berger A. Th1 and Th2 responses: what are they? BMJ 2000; 321(7258): 424. https://doi.org/10.1136/bmj.321.7258.424

7. Broadway DC, Grierson I, O'Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol 1994; 112(11):1437-1445. https://doi.org/10.1001/archopht.1994.01090230051020

8. Antonova A.V., Nikolaenko V.P., Brzheskiy V.V. IOP-lowering therapy and ocular surface in glaucoma. Part 1. The effects of drug substances of glaucoma medications on the ocular surface. Russian Journal of Clinical Ophthalmology 2020; 20(2):79-84. https://doi.org/10.32364/2311-7729-2020-20-2-79-84.

9. Terai N, Schlötzer-Schrehardt U, Lampel J, et al. Effect of latanoprost and timolol on the histopathology of the human conjunctiva. Br J Ophthalmol 2009; 93(2):219-224. https://doi.org/10.1136/bjo.2008.140186

10. Mohammed I, Kulkarni B, Faraj LA, Abbas A et al. Profiling ocular surface responses to preserved and non-preserved topical glaucoma medications: A 2-year randomized evaluation study. Clin Exp Ophthalmol 2020; 48(7):973-982. https://doi.org/10.1111/ceo.13814

11. Lee HJ, Jun RM, Cho MS, Choi KR. Comparison of the ocular surface changes following the use of two different prostaglandin F2α analogues containing benzalkonium chloride or polyquad in rabbit eyes. Cutan Ocul Toxicol 2015; 34(3):195-202. https://doi.org/10.3109/15569527.2014.944650

12. Guenoun JM, Baudouin C, Rat P, Pauly A, et al. In vitro study of inflammatory potential and toxicity profile of latanoprost, travoprost, and bimatoprost in conjunctiva-derived epithelial cells. Invest Ophthalmol Vis Sci 2005; 46(7):2444-2450. https://doi.org/10.1167/iovs.04-1331

13. Liang H, Baudouin C, Daull P, Garrigue JS, et al. In Vitro Corneal and Conjunctival Wound-Healing Assays as a Tool for Antiglaucoma Prostaglandin Formulation Characterization. Front Biosci (Landmark Ed) 2022; 27(5):147. https://doi.org/10.31083/j.fbl2705147

14. Yang Y, Huang C, Lin X, et al. 0.005% Preservative-Free Latanoprost Induces Dry Eye-Like Ocular Surface Damage via Promotion of Inflammation in Mice. Invest Ophthalmol Vis Sci 2018; 59(8):3375-3384. https://doi.org/10.1167/iovs.18-24013

15. Mocan MC, Uzunosmanoglu E, Kocabeyoglu S, Karakaya J, et al. The Association of Chronic Topical Prostaglandin Analog Use With Meibomian Gland Dysfunction. J Glaucoma 2016; 25(9):770-774. https://doi.org/10.1097/IJG.0000000000000495

16. Arita R, Itoh K, Maeda S, et al. Effects of long-term topical anti-glaucoma medications on meibomian glands. Graefes Arch Clin Exp Ophthalmol 2012; 250(8):1181-1185. https://doi.org/10.1007/s00417-012-1943-6

17. Jiang XY, Yang PS, Xiao O, et al. Effects of PPAR-γ and RXR-α on mouse meibomian gland epithelial cells during inflammation induced by latanoprost. Exp Eye Res 2022; 224:109251. https://doi.org/10.1016/j.exer.2022.109251

18. Agnifili L, Mastropasqua R, Fasanella V, et al. Meibomian Gland Features and Conjunctival Goblet Cell Density in Glaucomatous Patients Controlled With Prostaglandin/Timolol Fixed Combinations: A Case Control, Cross-sectional Study. J Glaucoma 2018; 27(4):364-370. https://doi.org/10.1097/IJG.0000000000000899

19. Rath A, Eichhorn M, Träger K, Paulsen F, et al. In vitro effects of benzalkonium chloride and prostaglandins on human meibomian gland epithelial cells. Ann Anat 2019; 222:129-138. https://doi.org/10.1016/j.aanat.2018.12.003

20. Pisella PJ, Debbasch C, Hamard P, et al. Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vitro study. Invest Ophthalmol Vis Sci. 2004; 45(5):1360-1368. https://doi.org/10.1167/iovs.03-1067

21. Aydin Kurna S, Acikgoz S, Altun A, Ozbay N, et al. The effects of topical antiglaucoma drugs as monotherapy on the ocular surface: a prospective study. J Ophthalmol 2014; 2014:460483. https://doi.org/10.1155/2014/460483

22. Hedengran A, Freiberg JC, Hansen PM, et al. Generic benzalkonium chloride-preserved travoprost eye drops are not identical to the branded polyquarternium-1-preserved travoprost eye drop: Effect on cultured human conjunctival goblet cells and their physicochemical properties. Acta Ophthalmol 2022; 100(7):819-827. https://doi.org/10.1111/aos.15163

23. Mastropasqua L, Agnifili L, Fasanella V, et al. Conjunctival goblet cells density and preservative-free tafluprost therapy for glaucoma: an in vivo confocal microscopy and impression cytology study. Acta Ophthalmol 2013; 91(5):e397-e405. https://doi.org/10.1111/aos.12131

24. Jappe U, Uter W, Menezes de Pádua CA, Herbst RA, et al. Allergic contact dermatitis due to beta-blockers in eye drops: a retrospective analysis of multicentre surveillance data 1993-2004. Acta Derm Venereol 2006; 86(6):509-514. https://doi.org/10.2340/00015555-0162

25. Singh S, Donthineni PR, Shanbhag SS, et al. Drug induced cicatrizing conjunctivitis: A case series with review of etiopathogenesis, diagnosis and management. Ocul Surf 2022; 24:83-92. https://doi.org/10.1016/j.jtos.2022.02.004

26. Vazirani J, Donthineni PR, Goel S, et al. Chronic cicatrizing conjunctivitis: A review of the differential diagnosis and an algorithmic approach to management. Indian J Ophthalmol 2020; 68(11):2349-2355. https://doi.org/10.4103/ijo.IJO_604_20

27. Zhang Y, Kam WR, Liu Y, Chen X, et al. Influence of Pilocarpine and Timolol on Human Meibomian Gland Epithelial Cells. Cornea 2017; 36(6):719-724. https://doi.org/10.1097/ICO.0000000000001181

28. Arici MK, Arici DS, Topalkara A, Güler C. Adverse effects of topical antiglaucoma drugs on the ocular surface. Clin Exp Ophthalmol 2000; 28(2):113-117. https://doi.org/10.1046/j.1442-9071.2000.00237.x

29. Knop E, Knop N, Millar T, Obata H, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011; 52(4):1938-1978 https://doi.org/10.1167/iovs.10-6997c

30. Kamath AP, Satyanarayana S, Rodrigues F. Ocular Surface Changes in Primary Open Angle Glaucoma with Long Term Topical Anti Glaucoma Medication. Med J Armed Forces India 2007; 63(4):341-345. https://doi.org/10.1016/S0377-1237(07)80011-6

31. Frezzotti P, Fogagnolo P, Haka G, et al. In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma. Acta Ophthalmol 2014;92(2):e133-e140. https://doi.org/10.1111/aos.12261

32. Delaney YM, Salmon JF, Mossa F, Gee B, et al. Periorbital dermatitis as a side effect of topical dorzolamide. Br J Ophthalmol 2002; 86(4):378-380. https://doi.org/10.1136/bjo.86.4.378

33. Hegde V, Robinson R, Dean F, Mulvihill HA, et al. Drug-induced ectropion: what is best practice? Ophthalmology 2007; 114(2):362-366. https://doi.org/10.1016/j.ophtha.2006.09.032

34. Sedlak L, Świerczyńska M, Borymska W, Zych M, et al. Impact of dorzolamide, benzalkonium-preserved dorzolamide and benzalkoniumpreserved brinzolamide on selected biomarkers of oxidative stress in the tear film. BMC Ophthalmol 2021; 21(1):319. https://doi.org/10.1186/s12886-021-02079-y

35. Li G, Akpek EK, Ahmad S. Glaucoma and Ocular Surface Disease: More than Meets the Eye. Clin Ophthalmol 2022; 16:3641-3649. https://doi.org/10.2147/OPTH.S388886

36. Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma 2002; 11(2):119-126. https://doi.org/10.1097/00061198-200204000-00007

37. Bhatti A, Singh G. Efficacy of three different formulations of brimonidine for control of intraocular pressure in primary open-angle glaucoma: A 6-week randomized trial. Oman J Ophthalmol 2018; 11(2):140-143. https://doi.org/10.4103/ojo.OJO_98_2016

38. Hopf S, Mercieca K, Pfeiffer N, Prokosch-Willing V. Brimonidine-associated uveitis — a descriptive case series. BMC Ophthalmol 2020; 20(1):489. https://doi.org/10.1186/s12886-020-01762-w

39. Helin M, Rönkkö S, Puustjärvi T, Teräsvirta M, et al. Conjunctival inflammatory cells and their predictive role for deep sclerectomy in primary open-angle glaucoma and exfoliation glaucoma. J Glaucoma 2011; 20(3):172-178. https://doi.org/10.1097/IJG.0b013e3181d9ccb0

40. Ghosh S, O'Hare F, Lamoureux E, Vajpayee RB, et al. Prevalence of signs and symptoms of ocular surface disease in individuals treated and not treated with glaucoma medication. Clin Exp Ophthalmol 2012; 40(7):675-681. https://doi.org/10.1111/j.1442-9071.2012.02781.x

41. Hong S, Lee CS, Seo KY, Seong GJ, et al. Effects of topical antiglaucoma application on conjunctival impression cytology specimens. Am J Ophthalmol 2006; 142(1):185-186. https://doi.org/10.1016/j.ajo.2006.02.056

42. Broadway DC, Grierson I, O'Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery. Arch Ophthalmol 1994; 112(11):1446-1454. https://doi.org/10.1001/archopht.1994.01090230060021

43. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol 2021; 105(Suppl 1):1-169. https://doi.org/10.1136/bjophthalmol-2021-egsguidelines

44. Landers J, Martin K, Sarkies N, Bourne R, et al. twenty-year followup study of trabeculectomy: risk factors and outcomes. Ophthalmology 2012; 119(4):694-702. https://doi.org/10.1016/j.ophtha.2011.09.043

45. Servat JJ, Bernardino CR. Effects of common topical antiglaucoma medications on the ocular surface, eyelids and periorbital tissue. Drugs Aging 2011; 28(4):267-282. https://doi.org/10.2165/11588830-000000000-00000

46. Walsh K, Jones L. The use of preservatives in dry eye drops. Clin Ophthalmol 2019; 13:1409-1425. https://doi.org/10.2147/OPTH.S211611

47. Goldstein MH, Silva FQ, Blender N, Tran T, et al. Ocular benzalkonium chloride exposure: problems and solutions. Eye (Lond) 2022; 36(2):361-368. https://doi.org/10.1038/s41433-021-01668-x

48. Hedengran A, Freiberg J, May Hansen P, et al. Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells. J Optom 2024; 17(1):100481. https://doi.org/10.1016/j.optom.2023.100481

49. Baudouin C, Labbé A, Liang H, Pauly A, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res 2010; 29(4): 312-334. https://doi.org/10.1016/j.preteyeres.2010.03.001

50. Nagstrup AH. The use of benzalkonium chloride in topical glaucoma treatment: An investigation of the efficacy and safety of benzalkonium chloride-preserved intraocular pressure-lowering eye drops and their effect on conjunctival goblet cells. Acta Ophthalmol 2023; 101 Suppl 278:3-21. https://doi.org/10.1111/aos.15808

51. Agnifili L, Fasanella V, Mastropasqua R, et al. In Vivo Goblet Cell Density as a Potential Indicator of Glaucoma Filtration Surgery Outcome. Invest Ophthalmol Vis Sci 2016; 57(7):2928-2935. https://doi.org/10.1167/iovs.16-19257

52. Amar N, Labbé A, Hamard P, Dupas B, et al. Filtering blebs and aqueous pathway an immunocytological and in vivo confocal microscopy study. Ophthalmology 2008; 115(7):1154-1161.e4. https://doi.org/10.1016/j.ophtha.2007.10.024

53. Martone G, Frezzotti P, Tosi GM, et al. An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol 2009; 147(4):725-735.e1. https://doi.org/10.1016/j.ajo.2008.10.019

54. Aihara M, Oshima H, Araie M; EXTraKT study group. Effects of Sof-Zia-preserved travoprost and benzalkonium chloride-preserved latanoprost on the ocular surface — a multicentre randomized singlemasked study. Acta Ophthalmol 2013; 91(1):e7-e14. https://doi.org/10.1111/j.1755-3768.2012.02565.x

55. Aihara M, Ikeda Y, Mizoue S, et al. Effect of Switching to Travoprost Preserved With SofZia in Glaucoma Patients With Chronic Superficial Punctate Keratitis While Receiving BAK-preserved Latanoprost. J Glaucoma 2016; 25(6):e610-e614. https://doi.org/10.1097/IJG.0000000000000265

56. Andole S, Senthil S. Ocular Surface Disease and Anti-Glaucoma Medications: Various features, Diagnosis, and Management Guidelines. Semin Ophthalmol. 2023; 38(2):158-166. https://doi.org/10.1080/08820538.2022.2094714

57. Anwar Z, Wellik SR, Galor A. Glaucoma therapy and ocular surface disease: current literature and recommendations. Current Opinion in Ophthalmology 2013; 24(2):136-143. https://doi.org/10.1097/icu.0b013e32835c8aba

58. Kahook MY. Travoprost Z ophthalmic solution with sofZia: clinical safety and efficacy. Expert Rev Ophthalmol [Internet] 2007; 2(3):363-368. http://dx.doi.org/10.1586/17469899.2.3.363

59. Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells. Adv Ther 2010; 27(11):837-845. https://doi.org/10.1007/s12325-010-0070-1

60. Uusitalo H, Kaarniranta K, Ropo A. Pharmacokinetics, efficacy and safety profiles of preserved and preservative-free tafluprost in healthy volunteers. Acta Ophthalmol Suppl (Oxf) 2008; 242:7-13. https://doi.org/10.1111/j.1755-3768.2008.01380.x

61. Nagornova Z.M., Kuroyedov A.V., Petrov S.Yu., Seleznev A.V., et al. The effect of topical hypotensive therapy on ocular surface and glaucoma surgery outcomes in patients with primary open-angle glaucoma. National Journal glaucoma 2019; 18(4):96-107. https://doi.org/10.25700/NJG.2019.04.08

62. Schlunck G, Meyer-ter-Vehn T, Klink T, Grehn F. Conjunctival fibrosis following filtering glaucoma surgery. Exp Eye Res 2016; 142:76-82. https://doi.org/10.1016/j.exer.2015.03.021

63. Boimer C, Birt CM. Preservative exposure and surgical outcomes in glaucoma patients: The PESO study. J Glaucoma 2013; 22(9):730-735. https://doi.org/10.1097/IJG.0b013e31825af67d

64. Agarwal HC, Sharma TK, Sihota R, Gulati V. Cumulative effect of risk factors on short-term surgical success of mitomycin augmented trabeculectomy. J Postgrad Med 2002; 48(2):92-96.

65. Lee S, Park DY, Huh MG, Cha SC. Influence of preoperative glaucoma medication on long-term outcomes of trabeculectomy. Sci Rep. 2024; 14(1):28341. https://doi.org/10.1038/s41598-024-79637-z

66. Wong JKW, Leung TK, Lai JS, Chan JC. Evaluation of Adverse Effects of Topical Glaucoma Medications on Trabeculectomy Outcomes Using the Glaucoma Medications Intensity Index. Ophthalmol Ther 2022; 11(1):387-401. https://doi.org/10.1007/s40123-021-00447-x

67. Chamard C, Larrieu S, Baudouin C, Bron A, Villain M, Daien V. Preservative-free versus preserved glaucoma eye drops and occurrence of glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008-2016. Acta Ophthalmol 2020; 98(7):e876-e881. https://doi.org/10.1111/aos.14410

68. Takihara Y, Inatani M, Ogata-Iwao M, et al. Trabeculectomy for openangle glaucoma in phakic eyes vs in pseudophakic eyes after phacoemulsification: a prospective clinical cohort study. JAMA Ophthalmol 2014; 132(1):69-76. https://doi.org/10.1001/jamaophthalmol.2013.5605

69. Takihara Y, Inatani M, Seto T, et al. Trabeculectomy with mitomycin for open-angle glaucoma in phakic vs pseudophakic eyes after phacoemulsification. Arch Ophthalmol 2011; 129(2):152-157. https://doi.org/10.1001/archophthalmol.2010.348

70. Mathew RG, Parvizi S, Murdoch IE. Success of trabeculectomy surgery in relation to cataract surgery: 5-year outcomes. Br J Ophthalmol 2019; 103(10):1395-1400. https://doi.org/10.1136/bjophthalmol-2018-312972

71. Torres-Costa S, Melo AB, Estrela-Silva S, Falcão-Reis F, et al. Effect of Prior Phacoemulsification Surgery in Trabeculectomy Surgery Outcomes. Clin Ophthalmol 2022; 16:357-367. https://doi.org/10.2147/OPTH.S348364

72. Supawavej C, Nouri-Mahdavi K, Law SK, Caprioli J. Comparison of results of initial trabeculectomy with mitomycin C after prior clearcorneal phacoemulsification to outcomes in phakic eyes. J Glaucoma 2013; 22(1):52-59. https://doi.org/10.1097/IJG.0b013e31821e8607

73. McMillan BD, Gross RL. Trabeculectomy first in pseudophakic eyes requiring surgery for medically-uncontrolled glaucoma. Surv Ophthalmol 2017; 62(1):104-108. https://doi.org/10.1016/j.survophthal.2016.05.004

74. Lamping KA, Belkin JK. 5-Fluorouracil and mitomycin C in pseudophakic patients. Ophthalmology 1995; 102(1):70-75. https://doi.org/10.1016/s0161-6420(95)31051-2

75. Five-year follow-up of the Fluorouracil Filtering Surgery Study. The Fluorouracil Filtering Surgery Study Group. Am J Ophthalmol 1996; 121(4):349-366. https://doi.org/10.1016/s0002-9394(14)70431-3

76. Gross RL, Feldman RM, Spaeth GL, et al. Surgical therapy of chronic glaucoma in aphakia and pseudophakia. Ophthalmology 1988; 95(9): 1195-1201. https://doi.org/10.1016/s0161-6420(88)33027-7

77. Broadway DC, Grierson I, Hitchings RA. Local effects of previous conjunctival incisional surgery and the subsequent outcome of filtration surgery. Am J Ophthalmol 1998; 125(6):805-818. https://doi.org/10.1016/s0002-9394(98)00045-2

78. Saika S, Yamanaka O, Baba Y, et al. Accumulation of latent transforming growth factor-beta binding protein-1 and TGF beta 1 in extracellular matrix of filtering bleb and of cultured human subconjunctival fibroblasts. Graefes Arch Clin Exp Ophthalmol 2001; 239(3):234-241. https://doi.org/10.1007/s004170100275

79. Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol 2020; 10(9):200223. https://doi.org/10.1098/rsob.200223

80. Wang PH, Huang BS, Horng HC, Yeh CC, et al. Wound healing. J Chin Med Assoc 2018; 81(2):94-101. https://doi.org/10.1016/j.jcma.2017.11.002

81. Seibold LK, Sherwood MB, Kahook MY. Wound modulation after filtration surgery. Surv Ophthalmol 2012; 57(6):530-550. https://doi.org/10.1016/j.survophthal.2012.01.008

82. Takai Y, Tanito M, Ohira A. Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle glaucoma, exfoliation glaucoma, and cataract. Invest Ophthalmol Vis Sci 2012; 53(1):241-247. https://doi.org/10.1167/iovs.11-8434

83. 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; 130(6):685-689. https://doi.org/10.1001/archophthalmol.2011.2799

84. Freedman J, Iserovich P. Pro-inflammatory cytokines in glaucomatous aqueous and encysted Molteno implant blebs and their relationship to pressure. Invest Ophthalmol Vis Sci 2013; 54(7):4851-4855. https://doi.org/10.1167/iovs.13-12274

85. Chua J, Vania M, Cheung CM, et al. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol Vis 2012; 18:431-438.

86. Balaiya S, Edwards J, Tillis T, Khetpal V, et al. Tumor necrosis factoralpha (TNF-α) levels in aqueous humor of primary open angle glaucoma. Clin Ophthalmol 2011; 5:553-556. https://doi.org/10.2147/OPTH.S19453

87. Dan J, Belyea D, Gertner G, Leshem I, et al. Plasminogen activator inhibitor-1 in the aqueous humor of patients with and without glaucoma. Arch Ophthalmol 2005; 123(2):220-224. https://doi.org/10.1001/archopht.123.2.220

88. Radius RL, Herschler J, Claflin A, Fiorentino G. Aqueous humor changes after experimental filtering surgery. Am J Ophthalmol 1980; 89(2):250-254. https://doi.org/10.1016/0002-9394(80)90119-1

89. Yu DY, Morgan WH, Sun X, et al. The critical role of the conjunctiva in glaucoma filtration surgery. Prog Retin Eye Res 2009; 28(5):303-328. https://doi.org/10.1016/j.preteyeres.2009.06.004

90. Liton PB, Luna C, Challa P, Epstein DL, et al. Genome-wide expression profile of human trabecular meshwork cultured cells, nonglaucomatous and primary open angle glaucoma tissue. Mol Vis 2006; 12:774-790.

91. Baudouin C, Kolko M, Melik-Parsadaniantz S, Messmer EM. Inflammation in Glaucoma: From the back to the front of the eye, and beyond. Prog Retin Eye Res 2021; 83:100916. https://doi.org/10.1016/j.preteyeres.2020.100916

92. Micera A, Quaranta L, Esposito G, et al. Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population. Adv Ther 2016; 33(2):252-267. https://doi.org/10.1007/s12325-016-0285-x

93. Taurone S, Ripandelli G, Pacella E, et al. Potential regulatory molecules in the human trabecular meshwork of patients with glaucoma: immunohistochemical profile of a number of inflammatory cytokines. Mol Med Rep 2015; 11(2):1384-1390. https://doi.org/10.3892/mmr.2014.2772

94. Mietz H, Jacobi PC, Welsandt G, Krieglstein GK. Trabeculectomies in fellow eyes have an increased risk of tenon's capsule cysts. Ophthalmology 2002; 109(5):992-997. https://doi.org/10.1016/s0161-6420(02)01014-x

95. Jung Y, Park HY, Lee NY, Yoo YS, et al. Difference in Outcomes between First-Operated vs. Fellow-Operated Eyes in Patients Undergoing Bilateral Trabeculectomies. PLoS One 2015; 10(8):e0136869. https://doi.org/10.1371/journal.pone.0136869

96. Kim S, Ahn Y, Lee Y, Kim H. Toxicity of Povidone-iodine to the ocular surface of rabbits. BMC Ophthalmol 2020; 20(1):359. https://doi.org/10.1186/s12886-020-01615-6

97. Klink T, Rauch N, Klink J, Grehn F. Influence of conjunctival suture removal on the outcome of trabeculectomy. Ophthalmologica 2009; 223(2):116-123. https://doi.org/10.1159/000181150