Abstract
Background
To date, the question whether there is a relationship between thrombophilic disorders and the development of nonarteritic ischemic optic neuropathy (NAION) remains controversial. We sought to investigate the prevalence of various coagulation defects among NAION patients <65 years of age, and to provide clinical guidelines for a selective thrombophilia screening.
Methods
A cohort of 35 patients <65 years of age with NAION and 70 controls matched for age and sex were prospectively screened for thrombophilic risk factors.
Results
Overall, thrombophilic defects were found to be present in 18 of 35 patients (51.4%) and in 12 of 70 (17.1%) controls (P = 0.0005). The most frequent coagulation disorders were increased levels of factor VIII (P = 0.015) and lipoprotein (a) (P = 0.005). Patients without cardiovascular risk factors had a statistically significant higher frequency of coagulation disorders than patients with these risk factors (P = 0.0059). There was a strong association of coagulation disorders and a personal or family history of thromboembolism (P = 0.028). Moreover, we determined the age of ≤55 years at the time of the first thromboembolic event or NAION as a strong predictor of underlying thrombophilia (P = 0.0002).
Conclusions
Our results indicate that thrombophilic disorders are associated with the development of NAION in specific subgroups of patients. Selective screening of young patients, subjects with a personal or family history of thromboembolism, and patients without cardiovascular risk factors may be helpful in identifying NAION patients with thrombophilic defects.
Similar content being viewed by others
References
Acheson JF, Sanders MD (1994) Coagulation abnormalities in ischemic optic neuropathy. Eye 8:89–92
Arnold AC (1995) Anterior ischemic optic neuropathy. Semin Ophthalmol 10:221–233. doi:10.3109/08820539509060976
Arnold AC (2003) Pathogenesis of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol 23:157–163. doi:10.1097/00041327-200306000-00012
Bank I, Libourel EJ, Middeldorp S et al (2005) Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost 3:79–84. doi:10.1111/j.1538-7836.2004.01033.x
Cursiefen C, Schönherr U, Schwender S, Grossmann R (1999) Recurrent optic nerve head infarctions associated with combined factor V Leiden- and factor II: G20210A-mutation. Acta Ophthalmol Scand 77:625–627. doi:10.1034/j.1600-0420.1999.770603.x
De Moerloose P, Boehlen F (2007) Inherited thrombophilia in arterial disease: a selective review. Semin Hematol 44:106–113. doi:10.1053/j.seminhematol.2007.01.008
De Stefano V, Rossi E, Paciaroni K, Leone G (2002) Screening for inherited thrombophilia: indications and therapeutic implications. Haematologica 87:1095–1108
Glueck CJ, Wang P, Bell H, Rangaray V, Goldenberg N (2004) Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylentetrahydrofolate reductase mutation. J Lab Clin Med 143:184–192. doi:10.1016/j.lab.2003.10.015
Hayreh SS, Joos KM, Podhajsky PA, Long CR (1994) Systemic diseases associated with nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 118:766–780
Holm J, Zöller B, Svensson PJ, Berntorp E, Erhardt L, Dahlbäck B (1994) Myocardial infarction associated with homozygous resistance to activated protein C. Lancet 344:952–953. doi:10.1016/S0140-6736(94)92302-7
Jacobson DM, Vierkant RA, Belongia EA (1997) Nonarteritic anterior ischemic optic neuropathy. A case-control study of potential risk factors. Arch Ophthalmol 115:1403–1407
Kim RJ, Becker RC (2003) Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 146:948–957. doi:10.1016/S0002-8703(03)00519-2
Knox DL, Kerrison JB, Green WR (2000) Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc 98:203–220
Koster T, Blann AD, Briet E (1995) Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 345:152–155. doi:10.1016/S0140-6736(95)90166-3
Krause M, Sonntag B, Klamroth R et al (2005) Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage. Thromb Haemost 93:867–871
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. doi:10.1016/j.ajo.2003.10.024
Kuhli-Hattenbach C, Scharrer I, Lüchtenberg M, Hattenbach LO (2008) Thrombophilic disorders associated with nonarteritic anterior ischemic optic neuropathy in patients <60 years of age. Klin Monatsbl Augenheilkd. In German. doi:10.1055/s-2008-1027488
Lane DA, Grant PJ (2000) Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 95:1517–1532
Loh BK, Lee SY, Goh KY (2007) Protein S deficiency manifesting simultaneously as central retinal artery occlusion, oculomotor nerve palsy, and systemic arterial occlusive diseases. Eye 21:684–686
Marcucci R, Sodi A, Giambene B et al (2007) Cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Blood Coagul Fibrinolysis 18:321–326. doi:10.1097/MBC.0b013e32809cc922
Martinelli I (2005) Von Willebrand Factor and Factor VIII as risk factors for arterial and venous thrombosis. Semin Hematol 42:49–55. doi:10.1053/j.seminhematol.2004.09.009
Mathews MK (2005) Nonarteritic anterior ischemic optic neuropathy. Curr Opin Ophthalmol 16:341–345. doi:10.1097/01.icu.0000188361.52166.93
Murata M, Saito T, Takahashi S, Ichinose A (1998) Plasma lipoprotein (a) levels are high in patients with central artery occlusion. Thromb Res 91:169–175. doi:10.1016/S0049-3848(98)00082-6
Nagy V, Facsko A, Takacs L et al (2004) Activated protein C resistance in anterior ischemic optic neuropathy. Acta Ophthalmol Scand 82:140–143. doi:10.1111/j.1600-0420.2004.00226.x
Nagy V, Steiber Z, Takacs L et al (2006) Thrombophilic screening for nonarteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 244:3–8. doi:10.1007/s00417-005-1154-5
Preechawat P, Bruce BB, Newman NJ, Biousse V (2007) Anterior ischemic optic neuropathy in patients younger than 50 years. Am J Ophthalmol 144:953–960. doi:10.1016/j.ajo.2007.07.031
Repka MX, Savino PJ, Schatz NJ et al (1983) Clinical profile and long-term implications of anterior ischemic optic neuropathy. Am J Ophthalmol 96:478–483
Ridker PM, Hennekens CH, Stampfer MJ (1993) A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA 270:2195–2199. doi:10.1001/jama.270.18.2195
Ridker PM, Stampfer MJ, Henneckens CH (1995) Plasma concentrations of lipoprotein(a) and the risk of future stroke. JAMA 273:1269–1273. doi:10.1001/jama.273.16.1269
Rosendaal FR, Varekamp I, Brocker-Vriends AH et al (1989) Mortality and causes of death in Dutch haemophiliacs, 1973-1986. Br J Haematol 71:71–76. doi:10.1111/j.1365-2141.1989.tb06277.x
Salomon O, Huna-Baron R, Kurtz S et al (1999) Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy. Ophthalmology 106:739–742. doi:10.1016/S0161-6420(99)90159-8
Sottilotta G, Oriana V, Latella et al (2007) Role of hyperhomocysteinemia in retinal vascular occlusive disease. Clin Appl Thromb Hemost 13:104–107. doi:10.1177/1076029606296423
Srinivasan S, Fern A, Watson WH, McColl MD (2001) Reversal of nonarteritic anterior ischemic optic neuropathy associated with coexisting primary antiphospholipid syndrome and Factor V Leiden Mutation. Am J Ophthalmol 131:671–673. doi:10.1016/S0002-9394(00)00873-4
Van der Meer FJ, Koster T, Vandenbroucke JP, Briët E, Rosendaal FR (1997) The Leiden Thrombophilia Study (LETS). Thromb Haemost 78:631–635
Author information
Authors and Affiliations
Corresponding author
Additional information
None of the authors has a proprietary or financial interest in any product mentioned. The corresponding author has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Rights and permissions
About this article
Cite this article
Kuhli-Hattenbach, C., Scharrer, I., Lüchtenberg, M. et al. Selective thrombophilia screening of patients with nonarteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 247, 485–490 (2009). https://doi.org/10.1007/s00417-008-0987-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-008-0987-0