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Editor,—We read with interest the paper recently published by Kawasaki et al.1They suggested that hyperhomocysteinaemia may have a role in the occurrence of non-arteritic anterior ischaemic optic neuropathy (NAION) in non-diabetic patients younger than 50 years, and raised the question of the frequency of the methylene tetrahydrofolate reductase (MTHFR) C677T mutation in this population.
There have been anecdotal reports of thrombotic tendencies in patients with NAION.2-4 Although NAION is most probably related to local factors compromising the posterior ciliary artery circulation at the optic nerve head (so called “disc at risk”), it is also possible that some systemic factors such as hyperhomocysteinaemia and the MTHFR C677T mutation may enhance local atherogenesis at the level of the posterior ciliary arteries, thereby precipitating the development of NAION in those at risk for the disease.3-6Kawasaki et al could not demonstrate any clear relation between hyperhomocysteinaemia and NAION. However, the blood sample used to measure the homocysteine was obtained years after the clinical event. Since homocysteinaemia fluctuates, it is possible that the authors may have underestimated the frequency of hyperhomocysteinaemia. We recently investigated prospectively the presence of hyperhomocysteinaemia and the MTHFR C677T mutation in patients with acute NAION.
Blood samples from 14 newly diagnosed patients with acute NAION presenting to our centre over a 1 year period (May 1998 to May 1999) were evaluated for serum creatinine, serum and red blood cell folate, B12, and total plasma homocysteine levels, as well as the C677T polymorphism in the MTFHR gene. There were 10 men and four women (13 white and one Asian), ranging in age from 28 to 68 years (mean aged 42.8 years). All patients had a disc at risk in the fellow eye. Five patients subsequently suffered NAION in their second eye. Four patients (28.5%) were heterozygous and one was homozygous for the C677T mutation in the MTHFR gene, which does not differ from the frequency reported in the general population.3 Only one of these five mutation positive patients had bilateral NAION. The homocysteine level was within normal range in all 14 patients, as were the creatinine, folate, and B12 levels. Homocysteine levels were not higher in the mutation positive patients than in the mutation negative patients. Mutation positive and mutation negative patients did not differ with respect to clinical data concerning risk factors for NAION or coexisting vascular disease.
Although this is a small study, these results suggest that homocysteine and the C677T MTHFR polymorphism do not have a role in the occurrence of NAION. Our results are similar to those of Kawasakiet al and the frequency of the MTHFR mutation is not higher than in the general population. As recently re-emphasised,2 4 5 laboratory testing for hypercoagulable states in a patient with NAION without past medical history or family history of a thrombotic event would be unwarranted. However, it is still possible that for a given individual already at risk for AION, a thrombogenic predilection may be a trigger for an acute ischaemic event of the optic nerve head. If there are clinical findings suggestive of a thrombogenic tendency, such as recurrent thrombotic events or a family history of thrombosis, or if there is no disc at risk in the fellow eye in a younger patient without vascular risk factors, an investigation for hereditary and acquired thrombophilic markers may be justifiable.
This study was supported in part by a departmental grant (department of ophthalmology) from Research to Prevent Blindness, Inc, New York, New York, by core grant P30-EY06360 (department of ophthalmology) from the National Institute of Health, Bethesda, Maryland. Dr Newman is recipient of Research to Prevent Blindness Lew R Wasserman Merit Awards.
Editor,—We thank Biousse and colleagues for their comments on our article and their corroborative study. We agree that an extensive hypercoagulable evaluation is not warranted in patients with NAION who have typical risk factors, including older age. The yield from such an evaluation in young patients with NAION, especially those without known risk factors or those who suffer recurrent events, still needs further elucidation.