Total Plasma Homocysteine and Primary Open-angle Glaucoma GLORIA WANG, MD, FELIPE A. MEDEIROS, MD, BRUCE A. BARSHOP, MD, AND ROBERT N. WEINREB, MD ● PURPOSE: To evaluate total plasma homocysteine (tHcy) levels in patients diagnosed with primary open- angle glaucoma (POAG) and normal subjects. ● DESIGN: Case-control study. ● METHODS: This study involved 55 POAG patients, 16 patients with secondary open-angle glaucoma or angle- closure glaucoma (non-POAG group), and 39 control healthy subjects undergoing ocular surgery. All glaucoma patients had characteristic glaucomatous optic disk dam- age and visual field loss. Fasting tHcy concentrations of all study participants were determined using high-perfor- mance liquid chromatography. Analysis of variance was used to compare homocysteine levels among the three diagnostic groups, and multivariate analysis was con- ducted to assess the associations between tHcy and diagnostic group, age, gender, smoking status, systemic hypertension, hyperlipidemia, and cardiovascular or ce- rebrovascular disease. ● RESULTS: Mean  standard deviation of tHcy levels in POAG individuals, non-POAG patients and control subjects was 14.90  6.45 mol/l, 14.30  4.35 mol/l, and 14.81  4.56 mol/l, respectively (P  .93; ANOVA). No statistically significant difference was found in the proportion of patients with abnormal tHcy levels among the three diagnostic groups. In multivariate analysis, only age and positive smoking status were significantly correlated with total plasma homocysteine levels. ● CONCLUSION: No significant difference was found in plasma homocysteine levels among POAG patients and normal control individuals. (Am J Ophthalmol 2004; 137:401– 406. © 2004 by Elsevier Inc. All rights reserved.) T HE PATHOGENESIS OF OPTIC NERVE DAMAGE IN glaucoma remains poorly understood. Although in- traocular pressure is assumed to be the most impor- tant risk factor for the disease, there is accumulating evidence that vascular risk factors may also play a role. 1–3 Glaucomatous damage may be caused, or at least facili- tated, by inadequate perfusion of the optic nerve. Impaired microcirculation and abnormal perfusion may be linked to anatomical or functional abnormalities of the vessels responsible for the blood supply of the optic nerve head, or both, like arteriosclerosis or vascular dysregulations. 1,3 As a result of several epidemiologic studies, increased attention recently has been directed at studying the total plasma level of the amino acid homocysteine (tHcy) as a risk factor for various cardiovascular disorders. Hyperho- mocysteinemia has been identified as a possible risk factor for arteriosclerosis and for the development of symptom- atic peripheral vascular, cerebrovascular, and coronary heart disease. 4–9 Pooled results from retrospective studies indicate that fasting homocysteine concentrations in pa- tients with vascular disease are on average 30% higher than in normal subjects. 7 Moreover, hyperhomocysteine- mia has also been demonstrated to be a risk factor for retinal vascular disease, including central retinal vein and central retinal artery occlusions 10 –17 as well as for nonar- teritic ischemic optic neuropathy. 13,18 In a recent study, Leibovitch and associates 19 found higher levels of plasma homocysteine in pseudoexfoliative glaucoma patients compared with age-matched control subjects. However, to date, there has been only one study relating levels of homocysteine in patients with primary open-angle glaucoma (POAG). Using an enzyme-linked immunoassay (EIA), Bleich and coworkers 20 reported sig- nificantly higher plasma homocysteine levels in 18 patients with POAG compared with 19 control subjects. The assay of total homocysteine in biological fluids is complicated by the ease with which the amino acid forms disulfide bonds. Although EIA methods provide simple and rapid assessment of tHcy levels, high-performance liquid chro- matography (HPLC) may be more precise. 21–23 High- performance liquid chromatography has been shown to Accepted for publication Sept 12, 2003. InternetAdvance publication at ajo.com Sept 16, 2003. From the Departments of Ophthalmology (G.W., F.A.M., R.N.W.) and Pediatrics (B.A.B.), University of California, San Diego, San Diego, California. Inquiries to Robert N. Weinreb, MD, Hamilton Glaucoma Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0946 © 2004 BY ELSEVIER INC.ALL RIGHTS RESERVED. 0002-9394/04/$30.00 401 doi:10.1016/j.ajo.2003.09.041