Outflow facility and extent of angle closure in a porcine model

  • Ying Hong
  • Chao Wang
  • Ralitsa Loewen
  • Susannah Waxman
  • Priyal Shah
  • Si Chen
  • Hamed Esfandiari
  • Nils A. LoewenEmail author
Basic Science



To establish the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). This could create a model to investigate focal outflow regulation.


Twenty anterior segments of porcine eyes were assigned to five groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4), and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 h after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared.


Baseline outflow facilities of the five groups were similar (F = 0.922, p = 0.477). Occlusion of 360° induced a significant decrease in facility from baseline at all time-points (p ≤ 0.023 at 3, 12, 24, and 36 h). However, no difference from baseline was found in any of the partially occluded (0–270°) groups (F ≥ 0.067, p ≥ 0.296 at 3, 12, 24, and 36 h). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal.


Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. Ninety degrees of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.


Angle closure model Glaucoma Trabecular meshwork Outflow facility 



This study was funded by the Initiative to Cure Glaucoma of the Eye and Ear Foundation of Pittsburgh (NAL), by NEI Grant K08EY022737, by NIH CORE Grant P30 EY08098 to the Department of Ophthalmology, and an unrestricted grant from Research to Prevent Blindness, New York, NY.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. No animals were sacrificed for the purpose of doing research. An approval by an ethics committee or institutional animal care and use committee was not required.


  1. 1.
    Liang Y, Friedman DS, Zhou Q et al (2011) Prevalence and characteristics of primary angle-closure diseases in a rural adult Chinese population: the Handan eye study. Invest Ophthalmol Vis Sci 52:8672–8679CrossRefGoogle Scholar
  2. 2.
    Casson RJ, Newland HS, Muecke J et al (2007) Prevalence of glaucoma in rural Myanmar: the Meiktila Eye Study. Br J Ophthalmol 91:710–714CrossRefGoogle Scholar
  3. 3.
    Wright C, Tawfik MA, Waisbourd M, Katz LJ (2016) Primary angle-closure glaucoma: an update. Acta Ophthalmol 94:217–225CrossRefGoogle Scholar
  4. 4.
    Chen S, Lv J, Fan S et al (2017) Laser peripheral iridotomy versus laser peripheral iridotomy plus laser peripheral iridoplasty in the treatment of multi-mechanism angle closure: study protocol for a randomized controlled trial. Trials 18:130CrossRefGoogle Scholar
  5. 5.
    Foster PJ, Buhrmann R, Quigley HA, Johnson GJ (2002) The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol 86:238–242CrossRefGoogle Scholar
  6. 6.
    Nongpiur ME, Ku JYF, Aung T (2011) Angle closure glaucoma: a mechanistic review. Curr Opin Ophthalmol 22:96–101CrossRefGoogle Scholar
  7. 7.
    Nongpiur ME, Sakata LM, Friedman DS et al (2010) Novel association of smaller anterior chamber width with angle closure in Singaporeans. Ophthalmology 117:1967–1973CrossRefGoogle Scholar
  8. 8.
    Wang B-S, Narayanaswamy A, Amerasinghe N et al (2011) Increased iris thickness and association with primary angle closure glaucoma. Br J Ophthalmol 95:46–50CrossRefGoogle Scholar
  9. 9.
    Nongpiur ME, He M, Amerasinghe N et al (2011) Lens vault, thickness, and position in Chinese subjects with angle closure. Ophthalmology 118:474–479CrossRefGoogle Scholar
  10. 10.
    Arkell SM, Lightman DA, Sommer A et al (1987) The prevalence of glaucoma among Eskimos of northwest Alaska. Arch Ophthalmol 105:482–485CrossRefGoogle Scholar
  11. 11.
    Foster PJ, Baasanhu J, Alsbirk PH et al (1996) Glaucoma in Mongolia. A population-based survey in Hövsgöl province, northern Mongolia. Arch Ophthalmol 114:1235–1241CrossRefGoogle Scholar
  12. 12.
    Salmon JF, Mermoud A, Ivey A et al (1993) The prevalence of primary angle closure glaucoma and open angle glaucoma in Mamre, western Cape, South Africa. Arch Ophthalmol 111:1263–1269CrossRefGoogle Scholar
  13. 13.
    Foster PJ, Oen FT, Machin D et al (2000) The prevalence of glaucoma in Chinese residents of Singapore: a cross-sectional population survey of the Tanjong Pagar district. Arch Ophthalmol 118:1105–1111CrossRefGoogle Scholar
  14. 14.
    Thomas R, Parikh R, Muliyil J, Kumar RS (2003) Five-year risk of progression of primary angle closure to primary angle closure glaucoma: a population-based study. Acta Ophthalmol Scand 81:480–485CrossRefGoogle Scholar
  15. 15.
    Thomas R, George R, Parikh R et al (2003) Five year risk of progression of primary angle closure suspects to primary angle closure: a population based study. Br J Ophthalmol 87:450–454CrossRefGoogle Scholar
  16. 16.
    Shen SY, Wong TY, Foster PJ et al (2008) The prevalence and types of glaucoma in malay people: the Singapore Malay eye study. Invest Ophthalmol Vis Sci 49:3846–3851CrossRefGoogle Scholar
  17. 17.
    Sun X, Dai Y, Chen Y et al (2017) Primary angle closure glaucoma: what we know and what we don’t know. Prog Retin Eye Res 57:26–45CrossRefGoogle Scholar
  18. 18.
    Loewen RT, Brown EN, Roy P et al (2016) Regionally discrete aqueous humor outflow quantification using fluorescein canalograms. PLoS One 11:e0151754CrossRefGoogle Scholar
  19. 19.
    Loewen RT, Roy P, Park DB et al (2016) A porcine anterior segment perfusion and transduction model with direct visualization of the trabecular meshwork. Invest Ophthalmol Vis Sci 57:1338–1344CrossRefGoogle Scholar
  20. 20.
    Loewen RT, Brown EN, Scott G et al (2016) Quantification of focal outflow enhancement using differential canalograms. Invest Ophthalmol Vis Sci 57:2831–2838CrossRefGoogle Scholar
  21. 21.
    Bachmann B, Birke M, Kook D et al (2006) Ultrastructural and biochemical evaluation of the porcine anterior chamber perfusion model. Invest Ophthalmol Vis Sci 47:2011–2020CrossRefGoogle Scholar
  22. 22.
    Okabe M, Kitagawa K, Yoshida T et al (2013) Application of 2-octyl-cyanoacrylate for corneal perforation and glaucoma filtering bleb leak. Clin Ophthalmol 7:649–653CrossRefGoogle Scholar
  23. 23.
    Vote BJ, Elder MJ (2000) Cyanoacrylate glue for corneal perforations: a description of a surgical technique and a review of the literature. Clin Exp Ophthalmol 28:437–442CrossRefGoogle Scholar
  24. 24.
    Kusabara AA, Kasahara N (2017) Managing glaucoma drainage device tube leak with cyanoacrylate. Acta Ophthalmol 95:e662CrossRefGoogle Scholar
  25. 25.
    Guhan S, Peng S-L, Janbatian H et al (2018) Surgical adhesives in ophthalmology: history and current trends. Br J Ophthalmol.
  26. 26.
    García-Delpech S, Sanz-Marco E, Martinez-Castillo S et al (2013) Ahmed valve, suture-less implantation: a new approach to an easier technique. J Glaucoma 22:750–756CrossRefGoogle Scholar
  27. 27.
    Dang Y, Waxman S, Wang C et al (2017) Freeze-thaw decellularization of the trabecular meshwork in anex vivo eye perfusion model. PeerJ 5:e3629CrossRefGoogle Scholar
  28. 28.
    Dang Y, Loewen R, Parikh HA et al (2017) Gene transfer to the outflow tract. Exp Eye Res 158:73–84CrossRefGoogle Scholar
  29. 29.
    Abu-Hassan DW, Li X, Ryan EI et al (2014) Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma. Stem Cells 33:751–761CrossRefGoogle Scholar
  30. 30.
    Vranka JA, Acott TS (2016) Pressure-induced expression changes in segmental flow regions of the human trabecular meshwork. Exp Eye Res.
  31. 31.
    Brubaker RF (2004) Goldmann’s equation and clinical measures of aqueous dynamics. Exp Eye Res 78:633–637CrossRefGoogle Scholar
  32. 32.
    Gonzalez JM Jr, Hamm-Alvarez S, Tan JCH (2013) Analyzing live cellularity in the human trabecular meshwork. Invest Ophthalmol Vis Sci 54:1039–1047CrossRefGoogle Scholar
  33. 33.
    Dang Y, Waxman S, Wang C et al (2018) A porcine ex vivo model of pigmentary glaucoma. Sci Rep 8:5468CrossRefGoogle Scholar
  34. 34.
    Kaplowitz K, Bussel II, Honkanen R et al (2016) Review and meta-analysis of ab-interno trabeculectomy outcomes. Br J Ophthalmol 100:594–600CrossRefGoogle Scholar
  35. 35.
    Tamm ER (2009) The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res 88:648–655CrossRefGoogle Scholar
  36. 36.
    Karlova E, Zolotaryov A, Nikolayeva G (2009) Trabecular meshwork contribution to the uveoscleral outflow. Acta Ophthalmol 87(s244).
  37. 37.
    Toris CB, Gregerson DS, Pederson JE (1987) Uveoscleral outflow using different-sized fluorescent tracers in normal and inflamed eyes. Exp Eye Res 45:525–532CrossRefGoogle Scholar
  38. 38.
    Toris CB, Yablonski ME, Wang YL, Camras CB (1999) Aqueous humor dynamics in the aging human eye. Am J Ophthalmol 127:407–412CrossRefGoogle Scholar
  39. 39.
    Kleinstein RN, Fatt I (1977) Pressure dependency of transcleral flow. Exp Eye Res 24:335–340CrossRefGoogle Scholar
  40. 40.
    Keller KE, Bradley JM, Vranka JA, Acott TS (2011) Segmental versican expression in the trabecular meshwork and involvement in outflow facility. Invest Ophthalmol Vis Sci 52:5049–5057CrossRefGoogle Scholar
  41. 41.
    Cha EDK, Xu J, Gong L, Gong H (2016) Variations in active outflow along the trabecular outflow pathway. Exp Eye Res 146:354–360CrossRefGoogle Scholar
  42. 42.
    Yang C-YC, Liu Y, Lu Z et al (2013) Effects of Y27632 on aqueous humor outflow facility with changes in hydrodynamic pattern and morphology in human eyes. Invest Ophthalmol Vis Sci 54:5859–5870CrossRefGoogle Scholar
  43. 43.
    Swaminathan SS, Oh D-J, Kang MH, Rhee DJ (2014) Aqueous outflow: segmental and distal flow. J Cataract Refract Surg 40:1263–1272CrossRefGoogle Scholar
  44. 44.
    Hann CR, Bahler CK, Johnson DH (2005) Cationic ferritin and segmental flow through the trabecular meshwork. Invest Ophthalmol Vis Sci 46:1–7CrossRefGoogle Scholar
  45. 45.
    Chang JYH, Folz SJ, Laryea SN, Overby DR (2014) Multi-scale analysis of segmental outflow patterns in human trabecular meshwork with changing intraocular pressure. J Ocul Pharmacol Ther 30:213–223CrossRefGoogle Scholar
  46. 46.
    Stamer WD, Acott TS (2012) Current understanding of conventional outflow dysfunction in glaucoma. Curr Opin Ophthalmol 23:135–143CrossRefGoogle Scholar
  47. 47.
    Carreon T, van der Merwe E, Fellman RL, et al (2016) Aqueous outflow—a continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res 57:108–133Google Scholar
  48. 48.
    Goel M, Picciani RG, Lee RK, Bhattacharya SK (2010) Aqueous humor dynamics: a review. Open Ophthalmol J 4:52–59CrossRefGoogle Scholar
  49. 49.
    Vranka JA, Staverosky JA, Reddy AP et al (2018) Biomechanical rigidity and quantitative proteomics analysis of segmental regions of the trabecular meshwork at physiologic and elevated pressures. Invest Ophthalmol Vis Sci 59:246–259CrossRefGoogle Scholar
  50. 50.
    Vranka JA, Bradley JM, Yang Y-F et al (2015) Mapping molecular differences and extracellular matrix gene expression in segmental outflow pathways of the human ocular trabecular meshwork. PLoS One 10:e0122483CrossRefGoogle Scholar
  51. 51.
    Hann CR, Fautsch MP (2009) Preferential fluid flow in the human trabecular meshwork near collector channels. Invest Ophthalmol Vis Sci 50:1692–1697CrossRefGoogle Scholar
  52. 52.
    Johnson DH (1989) Does pigmentation affect the trabecular meshwork? Arch Ophthalmol 107:250–254CrossRefGoogle Scholar
  53. 53.
    Foster PJ, Aung T, Nolan WP et al (2004) Defining “occludable” angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in east Asian people. Br J Ophthalmol 88:486–490CrossRefGoogle Scholar
  54. 54.
    Levkovitch-Verbin H, Quigley HA, Martin KRG et al (2002) Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats. Invest Ophthalmol Vis Sci 43:402–410Google Scholar
  55. 55.
    Fu CT, Sretavan D (2010) Laser-induced ocular hypertension in albino CD-1 mice. Invest Ophthalmol Vis Sci 51:980–990CrossRefGoogle Scholar
  56. 56.
    Gherezghiher T, March WF, Nordquist RE, Koss MC (1986) Laser-induced glaucoma in rabbits. Exp Eye Res 43:885–894CrossRefGoogle Scholar
  57. 57.
    Ittner LM, Schwerdtfeger K, Kunz TH et al (2008) Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma. Clin Sci 114:49–58CrossRefGoogle Scholar
  58. 58.
    Mermoud A, Baerveldt G, Mickler DS et al (1994) Animal model for uveitic glaucoma. Graefes Arch Clin Exp Ophthalmol 232:553–560CrossRefGoogle Scholar
  59. 59.
    McMenamin PG, Steptoe RJ (1991) Normal anatomy of the aqueous humour outflow system in the domestic pig eye. J Anat 178:65–77Google Scholar
  60. 60.
    Waxman S, Wang C, Dang Y et al (2018) Structure-function changes of the porcine distal outflow tract in response to nitric oxide. Invest Ophthalmol Vis Sci 59:4886–4895CrossRefGoogle Scholar
  61. 61.
    Waxman S, Loewen RT, Dang Y et al (2018) High-resolution, three-dimensional reconstruction of the outflow tract demonstrates segmental differences in cleared eyes. Invest Ophthalmol Vis Sci 59:2371–2380CrossRefGoogle Scholar
  62. 62.
    Dang Y, Waxman S, Wang C et al (2017) Rapid learning curve assessment in an ex vivo training system for microincisional glaucoma surgery. Sci Rep 7:1605CrossRefGoogle Scholar
  63. 63.
    Dang Y, Wang C, Shah P et al (2018) Outflow enhancement by three different ab interno trabeculectomy procedures in a porcine anterior segment model. Graefes Arch Clin Exp Ophthalmol 256:1305–1312CrossRefGoogle Scholar
  64. 64.
    Parikh HA, Loewen RT, Roy P et al (2016) Differential canalograms detect outflow changes from trabecular micro-bypass stents and ab interno trabeculectomy. Sci Rep 6:34705CrossRefGoogle Scholar
  65. 65.
    Suarez T, Vecino E (2006) Expression of endothelial leukocyte adhesion molecule 1 in the aqueous outflow pathway of porcine eyes with induced glaucoma. Mol Vis 12:1467–1472Google Scholar
  66. 66.
    Tripathi RC (1971) Ultrastructure of the exit pathway of the aqueous in lower mammals: (a preliminary report on the “angular aqueous plexus”). Exp Eye Res 12:311–314CrossRefGoogle Scholar
  67. 67.
    Trott AT (1997) Cyanoacrylate tissue adhesives. An advance in wound care. JAMA 277:1559–1560CrossRefGoogle Scholar
  68. 68.
    Habib A, Mehanna A, Medra A (2013) Cyanoacrylate: a handy tissue glue in maxillofacial surgery: our experience in Alexandria, Egypt. J Maxillofac Oral Surg 12:243–247CrossRefGoogle Scholar
  69. 69.
    Adler N, Nachumovsky S, Meshulam-Derazon S, Ad-El D (2007) Skin graft fixation with cyanoacrylate tissue adhesive in burn patients. Burns 33:803CrossRefGoogle Scholar
  70. 70.
    Kozieł S, Kobryń K, Paluszkiewicz R et al (2015) Endoscopic treatment of gastric varices bleeding with the use of n-butyl-2 cyanoacrylate. Prz Gastroenterol 10:239–243CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  2. 2.Department of OphthalmologyPeking University Third HospitalBeijingChina
  3. 3.Department of Ophthalmology, Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.The Third Xiangya Hospital of Central South UniversityChangshaChina
  5. 5.Department of OphthalmologyNorthwestern UniversityChicagoUSA
  6. 6.Department of OphthalmologyUniversity of WürzburgWürzburgGermany

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