Skip to main content
SpringerLink
Log in

Kardiovaskuläre Risikofaktoren, Gerinnung und gerinnungswirksame Therapien bei retinalen Gefäßverschlusserkrankungen

Cardiovascular risk factors, haemostasis and antithrombotic treatment in retinal vessel occlusion

  • Leitthema
  • Published:
Die Ophthalmologie Aims and scope Submit manuscript

Zusammenfassung

Venöse und arterielle retinale Gefäßverschlüsse stellen in der Regel keine isolierte Augenerkrankung dar, sondern sind als Erkrankungen des höheren Lebensalters zumeist mit klassischen kardiovaskulären Risikofaktoren assoziiert. Da betroffene Patienten häufig auch ein erhöhtes Risiko für sonstige vaskuläre Erkrankungen wie etwa einen ischämischen Schlaganfall aufweisen, ist eine interdisziplinäre Abklärung kardiovaskulärer Risikofaktoren und systemischer Begleiterkrankungen bei allen Patienten essenziell. Weiterführende hämostaseologische Untersuchungen sind insbesondere bei solchen Patienten sinnvoll und indiziert, die kein typisches Risikoprofil aufweisen. Dies ist bei jungem Manifestationsalter und Fehlen konventioneller Risikofaktoren der Fall, ebenso bei Patienten mit erhöhter Wahrscheinlichkeit für ein Antiphospholipidsyndrom bei prädisponierender Grunderkrankung. Neuere Studien konnten einen Zusammenhang zwischen Gerinnungs- und Fettstoffwechselstörungen einerseits und der Manifestation sowohl venöser als auch arterieller retinaler Gefäßverschlüsse in bestimmten Subgruppen von Patienten eindeutig belegen. Therapeutische Ansätze, retinale Gefäßverschlüsse mit gerinnungswirksamen Medikamenten akut zu behandeln oder langfristig das ophthalmologische Rezidivrisiko durch antithrombotische Medikation zu reduzieren, haben sich bisher nicht durchgesetzt. Allerdings steht bei visusrelevanten arteriellen retinalen Gefäßverschlüssen innerhalb einer definierten Latenzzeit die intravenöse Thrombolyse zur Verfügung. Bei definierten Störungen des Gerinnungssystems kann die Gabe von Antithrombotika zur Senkung des allgemeinen vaskulären Risikos sinnvoll sein. Dieser Beitrag gibt einen Überblick über kardiovaskuläre Risikofaktoren, das allgemeine vaskuläre Risiko sowie den aktuellen Kenntnisstand zu ophthalmologisch relevanten Gerinnungs- und Fettstoffwechselstörungen bei Patienten mit venösen und arteriellen retinalen Gefäßverschlüssen.

Abstract

Venous and arterial retinal vascular occlusions are age-related disorders, generally associated with classical cardiovascular risk factors, rather than an isolated ocular disease. As affected patients often also have an increased general risk for other vascular diseases, such as ischemic stroke, an interdisciplinary clarification of cardiovascular risk factors and systemic comorbidities is essential for all patients. Extended hemostaseological investigations may be recommended in those patients who do not match the typical risk profile. Patients at a young age by the time of manifestation, without conventional risk factors as well as patients with an increased risk of developing antiphospholipid syndrome may require a selective clinical investigation including testing for thrombophilic risk factors. Recent studies have clearly demonstrated an association between coagulation and lipid metabolism disorders and the development of both retinal vein and artery occlusions in specific subgroups of patients. Therapeutic approaches to treat retinal vascular occlusions or reduce the long-term risk of recurrences with anticoagulant or antiplatelet drugs have not gained widespread acceptance. However, intravenous thrombolysis may be a valuable treatment option for central retinal artery occlusions within a short time to treatment therapeutic window. For defined disorders of the coagulation system, the administration of antithrombotic drugs to reduce the general vascular risk can be a reasonable approach. This article provides an overview of cardiovascular risk factors, the general vascular risk and the current state of knowledge on ophthalmologically relevant disorders of coagulation and lipid metabolism in patients with venous and arterial retinal vascular occlusions.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Arséne S, Delahousse B, Regina S, Le Lez M‑L, Pisella P‑J, Gruel Y (2005) Increased prevalence of factor V Leiden in patients with retinal vein occlusion and under 60 years of age. Thromb Haemost 94:101–106

    Article  PubMed  Google Scholar 

  2. Bertram B, Wolf S, Fisches H, Schulte K, Hoberg A, Reim M (1991) Lysebehandlung bei retinalen Arterienverschlüssen mit Plasminogen-Aktivator. Klin Monatsbl Augenheilkd 198:295–300

    Article  PubMed  CAS  Google Scholar 

  3. Bick RL (2003) Prothrombin G20210A mutation, antithrombin, heparin cofactor II, protein C, and protein S defects. Hematol Oncol Clin North Am 17:9–36

    Article  PubMed  Google Scholar 

  4. Belcaro G, Dual M, Bradford HD et al (2019) Recurrent retinal vein thrombosis: Prevention with aspirin, pycnogenol, ticlopidine, or sulodexide. Minerva Cardioangiol 67:109–114

    Article  PubMed  Google Scholar 

  5. Campello E, Spiezia L, Simioni P (2016) Diagnosis and management of factor V Leiden. Expert Rev Hematol 9:1139–1149

    Article  PubMed  CAS  Google Scholar 

  6. Callizo J, Feltgen N, Pantenburg S et al (2015) Cardiovascular risk factors in central retinal artery occlusion: Results of a prospective and standardized medical examination. Ophthalmology 122(9):1881–1888. https://doi.org/10.1016/j.ophtha.2015.05.044

    Article  PubMed  Google Scholar 

  7. Chen CS, Lee AW, Campbell B et al (2011) Efficacy of intravenous tissue-type plasminogen activator in central retinal artery occlusion: report from a randomized, controlled trial. Stroke 42:2229–2234

    Article  PubMed  CAS  Google Scholar 

  8. Cho KH, Kim CK, Oh K, Oh SW, Park KH, Park SJ (2017) Retinal vein occlusion as the surrogate marker for premature brain aging in young patients. Invest Ophthalmol Vis Sci 58(6):BIO82–BIO87. https://doi.org/10.1167/iovs.17-21413

    Article  PubMed  Google Scholar 

  9. Chowdhary RA, Siddiqui MAR, Moiz B, Ishaq S (2022) Combined central retinal artery and vein occlusion associated with antiphospholipid syndrome. BMJ Case Rep 15:e248425. https://doi.org/10.1136/bcr-2021-248425

    Article  Google Scholar 

  10. Christiansen CB, Torp-Pedersen C, Olesen JB et al (2018) Risk of incident atrial fibrillation in patients presenting with retinal artery or vein occlusion: a nationwide cohort study. BMC Cardiovasc Disord 18(1):91. https://doi.org/10.1186/s12872-018-0825-1

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dithmar S, Hansen LL, Holz FG (2003) Venöse retinale Verschlüsse. Ophthalmologe 100:561–177

    Article  PubMed  CAS  Google Scholar 

  12. Fateh-Moghadam S, Kawa M (2007) Retinal vein occlusion disease and platelet activation: Will anti platelet therapy be a promising therapeutic strategy for patients with retinal vein occlusion disease in the future? Thromb Haemost 97:169–170.9

    Article  PubMed  CAS  Google Scholar 

  13. Feltgen N, Neubauer A, Jurklies B et al (2006) Multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. EAGLE Study report no. 1. Graefes Arch Clin Exp Ophthalmol 244:950–956

    Article  PubMed  CAS  Google Scholar 

  14. Graham SL, Goldberg I, Murray B, Beaumont P, Chong BH (1996) Activated protein C resistance—Low incidence in glaucomatous optic disc haemorrhage and central retinal vein occlusion. Aust N Z J Ophthalmol 24:199–205

    Article  PubMed  CAS  Google Scholar 

  15. Gris JC, Ripart-Neveu S, Maugard C et al (1997) Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study. Thromb Haemost 77:1096–1103

    Article  PubMed  CAS  Google Scholar 

  16. Hattenbach LO, Kuhli-Hattenbach C, Scharrer I et al (2008) Intravenous thrombolysis with low dose recombinant tissue plasminogen activator in central retinal artery occlusion. Am J Ophthalmol 146:700–706

    Article  PubMed  CAS  Google Scholar 

  17. Hattenbach LO, Arndt CF, Lerche R (2009) Retinal vein occlusion and low-dose fibrinolytic therapy (R.O.L.F.): a prospective, randomized, controlled multicenter study of low-dose recombinant tissue plasminogen activator versus hemodilution in retinal vein occlusion. Retina 29(7):932–940

    Article  PubMed  Google Scholar 

  18. Hayreh SS, Zimmerman MB, Kimura A, Sanon A (2004) Central retinal artery occlusion. Retinal survival time. Exp Eye Res 78:723–736

    Article  PubMed  CAS  Google Scholar 

  19. Hernandez JL, Sanles I, Perez-Montes R et al (2020) Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion. Thromb Res 190:63–68

    Article  PubMed  CAS  Google Scholar 

  20. Karcioglu O, Yilmaz S, Afacan G et al (2021) An update of the efficacy and comparative characteristics of direct (new) oral anticoagulants (DOACs). Cardiovasc Hematol Agents Med Chem. https://doi.org/10.2174/1871525719666210914112402

    Article  Google Scholar 

  21. Kattah JC, Wang DZ, Reddy C (2002) Intravenous recombinant tissue-type plasminogen activatorthrombolysis in treatment of central retinal artery occlusion. Arch Ophthalmol 120:1234–1236

    PubMed  Google Scholar 

  22. Kuhli C, Hattenbach LO, Scharrer I, Koch F, Ohrloff C (2002) High prevalence of resistance to APC in young patients with retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 240:163–168

    Article  PubMed  Google Scholar 

  23. Kuhli C, Scharrer I, Koch F, Ohrloff C, Hattenbach LO (2004) Factor XII deficiency: a thrombophilic risk factor for retinal vein occlusion. Am J Ophthalmol 137:459–464

    Article  PubMed  CAS  Google Scholar 

  24. Kuhli C, Jochmans K, Scharrer I, Lüchtenberg M, Hattenbach LO (2006) Retinal vein occlusion associated with antithrombin deficiency secondary to a novel G9840C missense mutation. Arch Ophthalmol 124:1165–1169

    Article  PubMed  Google Scholar 

  25. Kuhli-Hattenbach C, Scharrer I, Lüchtenberg M, Hattenbach LO (2010) Thrombophilia and the risk of retinal vein occlusion. A subgroup analysis. Thromb Haemost 103:299–305

    Article  PubMed  CAS  Google Scholar 

  26. Kuhli-Hattenbach C, Hellstern P, Kohnen T, Hattenbach LO (2017) Platelet activation by ADP is increased in selected patients with anterior ischemic optic neuropathy or retinal vein occlusion. Platelets 2017(28):720–723

    Article  Google Scholar 

  27. Kuhli-Hattenbach C, Hellstern P, Miesbach W, Kohnen T, Hattenbach LO (2017) Multiple thrombophilic risk markers in patients <65 years of age with retinal vein occlusion. Ophthalmologe 114:1149–1154

    Article  PubMed  CAS  Google Scholar 

  28. Kuhli-Hattenbach C, Hellstern P, Nägele DK, Kohnen T, Hattenbach LO (2017) Prothrombin polymorphism A19911G, factor V HR2 haplotype A4070G, and plasminogen activator-inhibitor‑1 polymorphism 4G/5G and the risk of retinal vein occlusion. Ophthalmic Genet 38:413–417

    Article  PubMed  CAS  Google Scholar 

  29. Kuhli-Hattenbach C, Miesbach W, Lüchtenberg M, Kohnen T, Hattenbach LO (2017) Elevated lipoprotein (a) levels are an independent risk factor for retinal vein occlusion. Acta Ophthalmol 95:140–145

    Article  PubMed  CAS  Google Scholar 

  30. Lahey JM, Tunc M, Kearnea J et al (2002) Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology 109:126–131

    Article  PubMed  Google Scholar 

  31. Lavin P, Patrylo M, Hollar M, Espaillat KB, Kirshner H, Schrag M (2018) Stroke risk and risk factors in patients with central retinal artery occlusion. Am J Ophthalmol 196:96–100. https://doi.org/10.1016/j.ajo.2018.08.027

    Article  PubMed  Google Scholar 

  32. Leoncini G, Brutzele D, Signorello MG et al (2007) Platelet activation by collagen is increased in retinal vein oculusion. Thromb Haemost 97:218–227

    Article  PubMed  CAS  Google Scholar 

  33. Leoncini G, Signorello MG, Armani U, Piana A, Ghiglione D, Camicione P (2009) In retinal vein occlusion platelet response to thrombin is increased. Thromb Res 124:48–55

    Article  Google Scholar 

  34. Li M, Hu X, Huang J, Tan Y, Yang B, Tang Z (2016) Impact of retinal vein occlusion on stroke incidence: a meta-analysis. J Am Heart Assoc 5(12):e4703. https://doi.org/10.1161/JAHA.116.004703

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mac Grory MB, Nackenoff A, Poli S et al (2020) Intravenous fibrinolysis for central retinal artery occlusion: a cohort study and updated patient level meta-analysis. Stroke 51:2018–2025

    Article  PubMed  Google Scholar 

  36. Matsuura T, Kobayashi T, Asahina T, Kanayama N, Terao T (2001) Is factor XII deficiency related to recurrent miscarriage? Semin Thromb Hemost 27:115–120

    Article  PubMed  CAS  Google Scholar 

  37. Nedelmann M, Graef M, Weinand F et al (2015) Retrobulbar spot sign predicts thrombolytic treatment effects and etiology in central retinal artery occlusion. Stroke 46:2322–2324

    Article  PubMed  Google Scholar 

  38. Pacella F, Bongiovanni G, Malvasi M et al (2020) Impact of cardiovascular risk factors on incidence and severity of retinal vein occlusion. Clin Ter 171(6):e534–e538. https://doi.org/10.7417/CT.2020.2269

    Article  PubMed  CAS  Google Scholar 

  39. Passacquale G, Sharma P, Perera D, Ferro A (2022) Antiplatelet therapy in cardiovascular disease: Current status and future directions. Br J Clin Pharmacol. https://doi.org/10.1111/bcp.15221

    Article  PubMed  Google Scholar 

  40. Ponto KA, Elbaz H, Peto T, Laubert-Reh D, Binder H, Wild PS, Lackner K, Pfeiffer N, Mirshahi A (2015) Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study. J Thromb Haemost 13(7):1254–1263. https://doi.org/10.1111/jth.12982

    Article  PubMed  CAS  Google Scholar 

  41. Preterre C, Godeneche G, Vandamme X et al (2017) Management of acute central retinal artery occlusion: intravenous thrombolysis is feasible and safe. Int J Stroke 12:720–723

    Article  PubMed  Google Scholar 

  42. Rehak M, Krcova V, Slavik L, Fric E, Langova K, Ulehlova J, Rehak J (2010) The role of thrombophilia in patients with retinal vein occlusion and no systemic risk factors. Can J Ophthalmol 45:171–175

    Article  PubMed  Google Scholar 

  43. Renné T, Pozgajová M, Grüner S et al (2005) Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med 202:271–281

    Article  PubMed  PubMed Central  Google Scholar 

  44. Schmidt D, Schumacher M, Wakhloo AK (1992) Microcatheter urokinase infusion in central retinal artery occlusion. Am J Ophthalmol 113:429–434

    Article  PubMed  CAS  Google Scholar 

  45. Schnieder M, Fischer-Wedi CV, Bemme S et al (2021) The Retrobulbar spot sign and prominent middle limiting membrane as prognostic markers in non-arteritic retinal artery occlusion. J Clin Med. https://doi.org/10.3390/jcm10020338

    Article  PubMed  PubMed Central  Google Scholar 

  46. Schrag M, Youn T, Schindler J et al (2015) Intravenous fibrinolytic therapy in central retinal artery occlusion: a patient-level meta-analysis. JAMA Neurol 72:1148–1154

    Article  PubMed  Google Scholar 

  47. Schultheiss M, Hartig F, Spitzer MS et al (2018) Intravenous thrombolysis in acute central retinal artery occlusion—A prospective interventional case series. PLoS ONE 13:e198114

    Article  Google Scholar 

  48. Scott JA, Arnold JJ, Currie JM et al (2001) No excess of factor V:Q506 genotype but high prevalence of anticardiolipin antibodies without antiendothelial cell antibodies in retinal vein occlusion in young patients. Ophthalmologica 215:217–221

    Article  PubMed  CAS  Google Scholar 

  49. Seligson U, Lubetsky A (2001) Genetic susceptibility to venous thrombosis. N Engl J Med 344(16):1222–1231

    Article  Google Scholar 

  50. Song P, Xu Y, Zha M, Zhang Y, Rudan I (2019) Global epidemiology of retinal vein occlusion: A systematic review and meta-analysis of prevalence, incidence, and risk factors. J Glob Health 9(1):10427. https://doi.org/10.7189/jogh.09.010427

    Article  PubMed  PubMed Central  Google Scholar 

  51. Squizzato A, Manfredi S, Bozzato S et al (2010) Antithrombotic and fibrinolytic drugs for retinal vein occlusion: A systematic review and a call for action. Thromb Haemost 103:271–276

    Article  PubMed  CAS  Google Scholar 

  52. Sucker C, Litmathe J (2018) Orale Antikoagulation mit Vitamin K‑Antagonisten – ein Update. Wien Med Wochenschr 168(5–6):121–132

    Article  PubMed  Google Scholar 

  53. Sucker C, Litmathe J, Berthold HK (2019) Orale Antikoagulation bei Vorhofflimmern: Differentialtherapie mit Nicht-Vitamin-K-abhängigen oralen Antikoagulanzien (NOAK) und Vitamin-K-Antagonisten (VKA) [Oral anticoagulation in atrial fibrillation: differential therapy with non vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists (VKA)]. MMW Fortschr Med 161(Suppl 6):15–23

    Article  PubMed  Google Scholar 

  54. Wenzel DA, Kromer R, Poli S et al (2021) Optical coherence tomography-based determination of ischaemia onset—the temporal dynamics of retinal thickness increase in acute central retinal artery occlusion. Acta Ophthalmol 99:e247–e252. https://doi.org/10.1111/aos.14563

    Article  PubMed  Google Scholar 

  55. Xourgia E, Tektonidou MG (2022) An update on Antiphospholipid syndrome. Curr Rheumatol 23:84

    Google Scholar 

  56. Zotz RB, Sucker C, Gerhardt A (2009) Bedeutung thrombophiler Risikofaktoren für das Erst- und Rezidivthromboserisiko. Hämotherapie 13:3–19

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Augenheilkunde, Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland

    Claudia Kuhli-Hattenbach

  2. Medizinische Hochschule Brandenburg (MHB), Brandenburg an der Havel, Deutschland

    Christoph Sucker

  3. Medizinisches Versorgungszentrum (MVZ), COAGUMED Gerinnungszentrum, Tauentzienstr. 7 b/c, 10789, Berlin, Deutschland

    Christoph Sucker

  4. Universitäts-Augenklinik Göttingen, Göttingen, Deutschland

    Nicolas Feltgen

  5. Klinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

    Martin Spitzer & Maximilian Schultheiss

  6. Augenklinik des Klinikums Ludwigshafen, Ludwigshafen, Deutschland

    Lars-Olof Hattenbach

Authors
  1. Claudia Kuhli-Hattenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Sucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicolas Feltgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Spitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maximilian Schultheiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lars-Olof Hattenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Claudia Kuhli-Hattenbach or Christoph Sucker.

Ethics declarations

Interessenkonflikt

C. Sucker: Vorträge: Leo Pharma, Sanofi, STAGO, Werfen; Advisory Boards: Werfen. N. Feltgen: Consultant: Alimera Sciences, Chiesi, Novartis, Roche; Speaker: Allergan/AbbVie, Alimera, Apellis, Bayer, Heidelberg Engineering, Novartis, Roche. L.‑O. Hattenbach: Studienteilnahme, Referent/Berater: Novartis Pharma GmbH, Bayer AG, Pharm Allergan GmbH, Roche Pharma AG; Studienteilnahme Apellis, Chengdu Kanghong Biotech Co., Ltd. C. Kuhli-Hattenbach, M. Spitzer und M. Schultheiss geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Die Autoren Claudia Kuhli-Hattenbach und Christoph Sucker teilen sich die Erstautorenschaft.

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuhli-Hattenbach, C., Sucker, C., Feltgen, N. et al. Kardiovaskuläre Risikofaktoren, Gerinnung und gerinnungswirksame Therapien bei retinalen Gefäßverschlusserkrankungen. Ophthalmologie 119, 1129–1139 (2022). https://doi.org/10.1007/s00347-022-01751-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-022-01751-y

Schlüsselwörter

Keywords

Search

Navigation