The Relationship Among Concentrations Of Homocysteine, Vitamin B12, Folate And MTHFR C677T Polymorphisms In Retinal Vein Occlusion

Obiective: Homocysteine is a potentially risk factor for central retinal vein occlusion(CRVO) and branch retinal vein occlusion(BRVO), but this remains controversial. We measured fasting total plasma homocysteine(tHcy) concentrations immediately after RVO and in the convalescent period to investigate this controversy. Methods: 1. We measured fasting tHcy concentrations in 68 consecutive patients with CRVO and 68 controls, matched for age and gender, aged 50 years and over. Fasting venous blood samples were collected within three days after CRVO.2. We measured fasting tHcy concentrations in 36 consecutive patients with CRVO within three days, at 1 month, 3 months and 6 months after CRVO and once in 36 control subjects.3. We measured fasting tHcy concentrations in 42 consecutive patients with BRVO within three days of admission and at 1 month, 3 months and 6 months after BRVO and once in 42 control subjects.4. We measured fasting tHcy concentrations in 16 consecutive patients with CRVO within three days, at 1 month, 3 months and 6 months after CRVO and once in 16 control subjects. There are records of total plasma homocysteine, vitamin B12, and folate levels in 16 cases with CRVO before CRVO occurrence.In addion, vitamin B12, and folate levels and the presence of C677 T MTHFR polymorphisms were analyzed in all patients and controls. Results: 1. There were no significant differences(P=0.134) in mean plasma tHcy between CRVO patients(10.73±3.21 μmol/l) and controls(9.99±2.57 μmol/l), nor were there any statistically significant differences when subjects were categorized by ischemic and nonischemic CRVO. However, six patients(27.3%) in the ischemic group and three patients(6.5%) in the nonischemic group were found to have hyperhomocysteinemia(P=0.018). There were no statistically significant differences in serum folate(P=0.503) or vitamin B12 levels(P=0.419) between CRVO patients(folate, 5.97±2.06 ng/ml; vitamin B12, 411±122 pg/ml) and controls(folate, 6.18±1.42 ng/ml; vitamin B12, 427±115 pg/ml). The prevalence of the homozygous genotype of the MTHFR C677 T mutation was not significantly different in patients than in controls.2. Median tHcy concentrations was not significantly higher than in matched control subjects in the acute phase of CRVO(9.66 [10.75±4.09] versus 9.25 [9.96±4.02] μmol/l, P=0.371) and 1 month after CRVO(P=0.119). However, tHcy levels increased significantly in the convalescent period and were significantly higher than in control subjects at 3 months after CRVO(P=0.010) and 6 months after CRVO(P<0.001). Furthermore, the tHcy levels of the ischemic CRVO patients at 6 months after CRVO were significantly higher than in nonischemic CRVO patients(P=0.028). However, these observations did not appear to be explained by alteration in serum folate, vitamin B12 concentrations, and the MTHFR C677 T genotype.3. Median tHcy concentrations was not significantly higher than in matched control subjects in the acute phase of BRVO(10.27 [11.01±4.09] versus 9.31 [10.04±3.67] μmol/l, P=0.257). However, tHcy levels were a classical rise, reaching a peak on 1 month after BRVO and declining to normal values by 6 months after BRVO. In addition, the tHcy levels increased with increasing foveal center point thickness and this correlation was significant at all time points. However, these observations did not appear to be explained by alteration in serum folate, vitamin B12 concentrations, and the MTHFR C677 T genotype.4. Median tHcy concentrations were significantly higher than in matched control subjects before CRVO occurrence. Median tHcy levels temporarily fall in the acute phase, and then tHcy levels in the convalescent stage of CRVO would be expected to return to primary levels. However, these observations did not appear to be explained by alteration in serum folate, vitamin B12 concentrations, and the MTHFR C677 T genotype. Conclusions: The tHcy levels are not immediately elevated after RVO but increase in the convalescent period. It is possible that elevated tHcy levels may be caused by the disease process itself. These data support the hypothesis that raised tHcy concentrations are independent risk factor for CRVO.