Skip to main content

Advertisement

Log in

Intracameral concentrations of the fibrinolytic system components in patients with age-related macular degeneration

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To detect the intracameral concentrations and activities of plasminogen and other components of the fibrinolytic system, and to investigate whether those concentrations and activities are higher in patients with age-related macular degeneration (AMD) in comparison to healthy controls.

Methods

Prospective case series of 93 patients scheduled for standard phacoemulsification.

Results

Mean plasminogen activity in patients with non-exsudative AMD (n = 24) revealed to be 0.06 %N, in patients with exudative AMD (n = 7) 0.03 %N and in healthy controls (n = 43) 0.02 %N (p = 0.38, ANOVA). Plasminogen activator inhibitor I (PAI-1) was detected in neither group. Alpha2–antiplasmin activity was 1.61 U/ml in the non-exudative AMD group (n = 27), 0 U/ml in the exudative AMD group (n = 7) and 0.54 U/ml in the control group (n = 48) (p = 0.1, ANOVA). Concentrations of plasmin–a2–antiplasmin complex (PAP) were detected at levels of 17.91 ng/ml in the non-exudative AMD group (n = 11), of 16.6 ng/ml in the exudative AMD group (n = 5), and of 17.43 ng/ml in the control group (n = 14) (p = 0.92, ANOVA).

Conclusions

Plasminogen is present with a very low activity in aqueous humor. There are no significant differences in aqueous humor concentrations or activities of plasminogen and other components of the fibrinolytic system between patients with non-exudative AMD, exudative AMD, and healthy controls. Further studies should investigate vitreous samples instead of aqueous humor samples. A careful and accurate workup of obtained intraocular fluids is needed to detect the low concentrations and activities of the parameters analyzed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Schmidt JC, Mennel S, Hörle S, Meyer CH (2006) High incidence of vitreomacular traction in recurrent choroidal neovascularization after repeated photodynamic therapy. Br J Ophthalmol 90(11):1361–1362

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Schulze S, Hoerle S, Mennel S, Kroll P (2008) Vitreomacular traction and exudative age-related macular degeneration. Acta Ophthalmol 86:470–481

    Article  PubMed  Google Scholar 

  3. Krebs I, Hagen S, Haas P, Glittenberg C, Binder S (2009) The vitreo-retinal interface in macular diseases. Spektrum Augenheilkd 23:2–11

    Article  Google Scholar 

  4. Schulze S, Neugebauer A, Kroll P (2010) Appearance of age-related macular degeneration in vitrectomized and nonvitrectomized eyes: an intraindividual case study. Acta Ophthalmol. doi:10.1111/j.1755-3768.2010.01929.x

    PubMed  Google Scholar 

  5. Mennel S, Meyer CH, Schmidt JC (2011) The role of the vitreous in the pathogenesis of age-related macular degeneration. Klin Monatsbl Augenheilkd 228:460–464

    Article  CAS  PubMed  Google Scholar 

  6. Stefansson E (2009) Physiology of vitreous surgery. Graefes Arch Clin Exp Ophthalmol 247:147–163

    Article  PubMed  Google Scholar 

  7. Ikeda T, Sawa H, Koizumi K, Yasuhara T, Yamasaki T (2000) Pars plana vitrectomy for regression of choroidal neovascularization with age-related macular degeneration. Acta Ophthalmol Scand 78:460–464

    Article  CAS  PubMed  Google Scholar 

  8. Gandorfer A (2009) Objective of pharmacologic vitreolysis. Dev Ophthalmol 44:1–6

    Article  CAS  PubMed  Google Scholar 

  9. Hesse L, Nebeling B, Schroeder B, Heller G, Kroll P (2000) Induction of posterior vitreous detachment in rabbits by intravitreal injection of tissue plasminogen activator following cryopexy. Exp Eye Res 70(1):31–39

    Article  CAS  PubMed  Google Scholar 

  10. Cachulo L, Silva R, Fonseca P, Pires I, Carvajal-Gonzalez S, Bernardes R, Cunha-Vaz JG (2011) Early markers of choroidal neovascularization in the fellow eye of patients with unilateral exudative age-related macular degeneration. Ophthalmologica 225:144–149

    Article  PubMed  Google Scholar 

  11. Bertelmann T, Kicova N, Kohlberger L, Spychalska M, Strodthoff S, Irle S, Mennel S (2012) Sampling aqueous humor: anterior segment anatomy, anesthetic and surgical technique, and rates of yield. Ophthalmic Res 47:214–219

    Article  PubMed  Google Scholar 

  12. Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A, Mishima HK (2008) Aqueous humor levels of cytokines are correlated to vitreous levels and severity of macular edema in branch retinal vein occlusion. Eye (Lond) 22:42–48

    Article  CAS  Google Scholar 

  13. O’Rourke J, Taylor DM, Wang Y (2004) Compact bulb pipette simplifies paracentesis. Ophthalmic Surg Lasers Imag 35:172–173

    Google Scholar 

  14. Noma H, Funatsu H, Mimura T, Harino S, Hori S (2010) Aqueous humor levels of vasoactive molecules correlate with vitreous levels and macular edema in central retinal vein occlusion. Eur J Ophthalmol 20(2):402–409

    PubMed  Google Scholar 

  15. Ecker SM, Hines JC, Pfahler SM, Glaser BM (2011) Aqueous cytokine and growth factor levels do not reliably reflect those levels found in the vitreous. Mol Vis 17:2856–2863

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Pfister M, Koch FH, Cinatl J, Rothweiler F, Schubert R, Singh P, Ackermann H, Koss MJ (2012) Cytokine determination from vitreous samples in retinal vascular diseases. Ophthalmologe [Epub ahead of print]. doi:10.1007/s00347-012-2719-4

    Google Scholar 

  17. Pleyer U, Ruokonen P (2010) Kammerwasseranalyse in der Diagnostik intraokulärer Entzündungen. Klein Monatsbl Augenheilkd 227:953–960

    Article  CAS  Google Scholar 

  18. Kotschy M, Kaluzny J, Kaniasty M, Zekanowska E, Kopinska E (1996) Tissue plasminogen activator (t-PA) in aqueous humor of patients with cataract. Klin Oczna 98(3):201–203

    CAS  PubMed  Google Scholar 

  19. Bertelmann T, Kicova N, Messerschmidt-Roth A, Irle S, Sekundo W, Mennel S (2011) The vitreomacular interface in retinal vein occlusion. Acta Ophthalmol 89:e327–e331

    Article  PubMed  Google Scholar 

  20. Gella L, Raman R, Kulothungan V, Sharma T (2012) Prevalence of posterior vitreous detachment in the population with type II diabetes mellitus and its effect on diabetic retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular genetic study SN-DREAMS report no. 23. Jpn J Ophthalmol 56:262–267

    Article  PubMed  Google Scholar 

  21. Sebag J (2004) Anomalous posterior vitreous detachment: a unifying concept in vitreo-retinal diseases. Graefes Arch Clin Exp Ophthalmol 242:690–698

    Article  CAS  PubMed  Google Scholar 

  22. Krebs I, Brannath W, Glittenberg C, Zeiler F, Sebag J, Binder S (2007) Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration? Am J Ophthalmol 144:741–746

    Article  PubMed  Google Scholar 

  23. Weber-Krause B, Eckardt U (1996) Incidence of posterior vitreous detachment in eyes with and without age-related macular degeneration. An ultrasonic study. Ophthalmologe 93(6):660–665

    Article  CAS  PubMed  Google Scholar 

  24. Mojana F, Cheng L, Bartsch DU, Silva GA, Kozak I, Nigam N, Freeman WR (2008) The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol 146(2):218–227

    Article  PubMed Central  PubMed  Google Scholar 

  25. Lee SJ, Lee CS, Koh HJ (2009) Posterior vitreomacular adhesion and risk of exudative age-related macular degeneration: paired eye study. Am J Ophthalmol 147(4):621–626

    Article  PubMed  Google Scholar 

  26. Robison CD, Krebs I, Binder S, Barbazetto IA, Kotsolis AI, Yannuzzi LA, Sadun AA, Sebag J (2009) Vitreomacular adhesion in active and end-stage age-related macular degeneration. Am J Ophthalmol 148:79–82

    Article  PubMed  Google Scholar 

  27. Krebs I, Glittenberg C, Zeiler F, Binder S (2011) Spectral domain optical coherence tomography for higher precision in the evaluation of vitreoretinal adhesions in exudative age-related macular degeneration. Br J Ophthalmol 95(10):1415–1418

    Article  PubMed  Google Scholar 

  28. Gawecki M, Doroszkiewicz M, Rydzewski J (2010) Age related macular degeneration and presence of posterior vitreous detachment. Klin Oczna 112(7–9):210–212

    PubMed  Google Scholar 

  29. Machemer R, Buettner H, Norton EW, Parel JM (1971) Vitrectomy: a pars plana approach. Trans Am Acad Opthalmol Otolaryngol 75(4):813–820

    CAS  Google Scholar 

  30. Sakamoto T, Ishibashi T (2009) Visualizing vitreous in vitrectomy by triamcinolone. Graefes Arch Clin Exp Ophthalmol 247(9):1153–1163

    Article  CAS  PubMed  Google Scholar 

  31. Sakamoto T, Sheu SJ, Arimura N, Sameshima S, Shimura M, Uemura A, Kawano H, Wu TT, Kubota T, Sohma R, Noda Y (2010) Vitrectomy for exudative age-related macular degeneration with vitreous hemorrhage. Retina 30(6):856–864

    Article  PubMed  Google Scholar 

  32. Roller AB, Mahajan VB, Boldt HC, Abramoff MD, Russell SR, Folk JC (2010) Effects of vitrectomy on age-related macular degeneration. Ophthalmology 117(7):1381–1386

    Article  PubMed  Google Scholar 

  33. Sonoda KH, Sakamoto T, Enaida H, Miyazaki M, Noda Y, Nakamura T, Ueno A, Yokoyama M, Kubota T, Ishibashi T (2004) Residual vitreous cortex after surgical posterior vitreous separation visualized by intravitreous triamcinolone acetonide. Ophthalmology 111(2):226–230

    Article  PubMed  Google Scholar 

  34. Stalmans P, Benz MS, Gandorfer A, Kampik A, Girach A, Pakola S, Haller JA, MIVI-TRUST Study Group (2012) Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 367:606–615

    Article  CAS  PubMed  Google Scholar 

  35. Immonen I, Stephens RW, Salonen EM, Laatikainen L, Sim PS, Vaheri A (1989) Tissue-type plasminogen activator in subretinal fluid. Curr Eye Res 8:249–252

    Article  CAS  PubMed  Google Scholar 

  36. Clausen R, Weller M, Hilgers RD, Heimann K, Wiedemann P (1990) Quantitative determinations of 5 vitreal proteins in the normal vitreous body and proliferative retinal diseases. Fortschr Ophthalmol 87:283–286

    CAS  PubMed  Google Scholar 

  37. Bresgen M, Martiny B, Weller M, Heimann K, Wiedemann P (1991) Analysis of the protein pattern in physiologic and pathologic vitreous bodies by electrophoresis and immunologic identification. Fortschr Ophthalmol 88:665–670

    CAS  PubMed  Google Scholar 

  38. Weller M (1997) Plasminogen in proliferative vitreoretinal disorders. Br J Ophthalmol 81:590–594

    Article  PubMed Central  PubMed  Google Scholar 

  39. Malukiewicz-Wisniewska G, Kotchy M (1999) Fibrinolytic activity of subretinal fluid after cryopexy. Eur J Ophthalmol 9:291–296

    CAS  PubMed  Google Scholar 

  40. Franceschetti A, Eichenberger E (1959) Fibrinolyse im Kammerwasser menschlicher und tierischer Augen. Brevès Communications–Kurze Mitteilungen–Brief Reports 15.IV, pp 130–131

  41. Wang Y, Taylor DM, Smalley DM, Cone RE, O’Rourke J (1994) Increased basal levels of free plasminogen activator activity found in human aqueous humor. Invest Ophthalmol Vis Sci 35:3561–3566

    CAS  PubMed  Google Scholar 

  42. Giedrojc J, Stankiewicz A, Walkowiak M, Galar M, Bielawiec M (1996) Tissue plasminogen activator and plasminogen activator inhibitor in aqueous humor. Klin Oczna 98(4):283–285

    CAS  PubMed  Google Scholar 

  43. Medcalf RL (2007) Fibrinolysis, inflammation, and regulation of the plasminogen activating system. J Thromb Haemost 5(Suppl 1):132–142

    Article  CAS  PubMed  Google Scholar 

  44. Rijken DC, Lijnen HR (2009) New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost 7:4–13

    Article  CAS  PubMed  Google Scholar 

  45. Ulrich JN, Spannagel M, Kampik A, Gandorfer A (2008) Components of the fibrinolytic system in the vitreous body in patients with vitreoretinal disorders. Clin Exp Ophthalmol 36:431–436

    Google Scholar 

  46. Esser P, Heimann K, Bartz-Schmidt KU, Walter P, Krott R, Weller M (1997) Plasminogen in proliferative vitreoretinal disorders. Br J Ophthalmol 81:590–594

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Tripathi BJ, Geanon JD, Tripathi RC (1987) Distribution of tissue plasminogen activator in human and monkey eyes. An immunohistochemical study. Ophthalmology 94(11):1434–1438

    Article  CAS  PubMed  Google Scholar 

  48. Tripathi RC, Park JK, Tripathi BJ, Milliard CB (1988) Tissue plasminogen activator in human aqueous humor and its possible therapeutic significance. Am J Ophthalmol 106(6):719–722

    CAS  PubMed  Google Scholar 

  49. Tripathi BJ, Tripathi RC, Geanon JD (1988) Tissue plasminogen activator in the lens. Ophthalmic Res 20(3):160–163

    Article  CAS  PubMed  Google Scholar 

  50. Steinkamp GWK, Hattenbach LO, Heider HW, Scharrer I (1993) Gewebsplasminogenaktivator und PAI. Ophthalmologe 90:73–75

    CAS  PubMed  Google Scholar 

  51. Hattenbach L, Allers A, Gümbel H, Scharrer I, Koch F (1999) Vitreous concentrations of t-PA and plasminogen activator inhibitor are associated with VEGF in proliferative diabetic retinopathy. Retina 19:383–389

    Article  CAS  PubMed  Google Scholar 

  52. Kapiotis S, Speiser W (1999) Synthese und Umsatzstörungen des Plasminogenaktivatorinhibitor Typ 1. In: Mueller-Berghaus G, Poetzsch B (eds) Hämostasiologie – Molekulare und zelluläre Mechanismen, Pathophysiologie und Klinik. Springer, Berlin, Kap. 51

    Google Scholar 

  53. Stief TW, Richter A, Maisch B, Renz H (2009) Monitoring of functional plasminogen in the blood of patients on fibrinolysis. Clin Appl Thromb Hemost 15(3):297–308

    Article  CAS  PubMed  Google Scholar 

  54. Immonen I, Salonen E, Salonen EM, Laatikainen L, Sim PS, Vaheri AL (1988) Plasmin in subretinal fluid. Acta Ophthalmol 66:647–651

    Article  CAS  Google Scholar 

  55. Pfeiffer A, Spranger J, Meyer-Schwickerath R, Schatz H (1997) Growth factor alterations in advanced diabetic retinopathy. Diabetes 46(Suppl 2):26–30

    Article  Google Scholar 

Download references

Acknowledgment

We thank Reka Bölöni, MD, Konstantinos Droutsas, MD, Stephan Schulze, MD, and Nadja Weber, MD, for their contribution by sampling AH.

Disclosure statement

There was no sponsor or funding organization involved in this study. The authors indicate no financial conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Bertelmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bertelmann, T., Spychalska, M., Kohlberger, L. et al. Intracameral concentrations of the fibrinolytic system components in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 251, 2697–2704 (2013). https://doi.org/10.1007/s00417-013-2374-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-013-2374-8

Keywords

Navigation