Prothrombotic and vascular risk factors in NAION

Abstract

Salomon et al1Salomon O. Huna-Baron R. Kurtz S. et al.Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy.Ophthalmology. 1999; 106: 739-742Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar studied 61 patients with nonarteritic anterior ischemic optic neuropathy (NAION) and 90 consecutive control patients and found no association between the disease studied and three prothrombotic genetic mutations. These risk factors were the factor V Leiden mutation (FVL) G1691A, prothrombin gene mutation (PGM) G20210A, and the methylenetetrahydrofolate reductase mutation (MTHFR) C677T. However, although the presence or absence of the genetic mutations for FVL and PGM may directly reflect their risk in causing thrombotic events, it is less clear that the absence of the MTHFR mutation decreases risk of thrombosis. If one can apply lessons learned about small vessel disease in the orbit and optic nerve head from the stroke literature, then several recent studies deserve mention. Markus et al2Markus H.S. Ali N. Swaminathan R. et al.A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease.Stroke. 1997; 28: 1739-1743Crossref PubMed Scopus (169) Google Scholar studied the relationship between MTHFR genotype and HC[e] with cerebrovascular disease and found no association. However, they did find a strong association between MTHFR and plasma HC[e]. The results of Kostulas et al3Kostulas K. Crisby M. Huang W.X. et al.A methylenetetrahydrofolate reductase gene polymorphism in ischaemic stroke and in carotid artery stenosis.Eur J Clin Invest. 1998; 28: 285-289Crossref PubMed Scopus (56) Google Scholar concurred with the previous report. They studied 126 patients with transient ischemic attack or stroke and 70 patients with carotid artery stenosis. They did not find an association with MTHFR in either patient group, but also did not find a correlation between MTHFR genotype and elevated HC[e] levels. Another large study found an independent association between HC[e] and carotid wall thickening, but not the MTHFR genotype or folate status.4McQuillan B.M. Beilby J.P. Nidorf M. et al.Hyperhomocysteinemia but not the C677T mutation of methylenetetrahydrofolate reductase is an independent risk determinant of carotid wall thickening. The Perth Carotid Ultrasound Disease Assessment Study.Circulation. 1999; 99: 2383-2388Crossref PubMed Scopus (201) Google Scholar Last, in a small series of 28 patients 18 years of age or younger, no association was found between stroke and the MTHFR mutation.5Akar N. Akar E. Deda G. et al.Factor V1691 G-A, prothrombin 20210 G-A, and methylenetetrahydrofolate reductase 677 C-T variants in Turkish children with cerebral infarct.J Child Neurol. 1999; 14: 749-751Crossref PubMed Scopus (63) Google Scholar It appears likely that cerebrovascular disease is related to HC[e], whereas the association with MTHFR is less clear. This is probably because of nongenetic influences on HC[e] such as folate concentration, among others. The results of Salomon et al should not dissuade us from investigating further whether the HC[e] pathway is linked to the development of NAION.