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Hyperhomocysteinemia and BRVO
Letters to the Editor Reference 1. Augsburger JJ, Vrabec TR. Impact of delayed treatment in growing posterior uveal melanomas. Arch Ophthalmol 1993; 111:1382– 6.
Hyperhomocysteinemia and BRVO Dear Editor: The article by Weger et al1 deals with the apparent Caucasian methylenetetrahydrofolate reductase (MTHFR) genotype data. The odds ratio for MTHFR 677CT/CC of 0.81 (as shown in their Table 3) was rather low. We analyzed 18 patients with branch retinal vein occlusion of AfricanAmerican (AA) ancestry from our eye clinic for the MTHFR C677T polymorphism and found that 6 patients were of the 677CT genotype, 0 of the 677TT genotype, and 12 of the 677CC genotype, giving a 677CT heterozygosity of 33%. However, when we analyzed 1472 AA control infants, we found 246 with the 677CT genotype, 20 with the 677TT genotype, and 1206 with the 677CC genotype, giving a 677CT heterozygosity of 16.7%. Thus, the 677CT genotype frequency in our AA patients was twice that found in the controls. Although our data were not statistically significant, probably due to a small sample size, nonetheless the odds ratio was 2.4, with a 95% confidence interval of 0.81–7.1, a chi-square value of 2.31, and a P value of 0.12. Based on our observations, we feel that there was a trend of increasing 677CT heterozygosity in the branch retinal vein occlusion patients relative to controls, at least in the AA ethnicity, the significance of which remains to be elucidated. Could the polymorphism relationship with branch retinal vein occlusion be ethno-specific? We are not sure because our MTHFR polymorphism data were too sparse to report from the Caucasian ethnicity. Larger data sets from both AA and Caucasian ethnicities would resolve the issue. If the relationship exists, we feel, a simple therapeutic folate regimen could alleviate the ocular vascular occlusions, at least in the AA community. KRISHNA YANAMANDRA, PHD, FACMG THEODORE F. THURMON, MD, FACMG JOSEPH A. BOCCHINI, JR, MD LAKSHMAN M. KOORAGAYALA, MD Shreveport, Louisiana Reference 1. Weger M, Stanger O, Deutschmann H, et al. Hyperhomocysteinemia, but not methylenetetrahydrofolate reductase C677T mutation, as a risk factor in branch retinal vein occlusion. Ophthalmology 2002;109:1105–9.
Author reply Dear Editor: We thank Dr Yanamandra and colleagues for their interest in our article. Recent studies have suggested hyperhomocysteinemia as a novel risk factor for retinal vein occlusion (RVO).1,2 Yet other investigators were unable to confirm these findings, resulting in an ongoing debate over the precise role of homocysteine in the pathogenesis of RVO.2,3 Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been shown to increase
plasma homocysteine levels, especially in the presence of suboptimal plasma folate levels. Previous studies focusing on the role of the MTHFR C677T mutation in RVO have yielded conflicting results.1,3–5 This, however, might reflect a considerable heterogeneity in the genotype distribution of the MTHFR C677T mutation among different populations.6 Study outcomes thus should be compared cautiously, especially if the number of study participants is small. Even if increased plasma homocysteine concentrations had consistently been found to be associated with RVO, a causal role and the potential benefits of lowering plasma homocysteine levels would still have to be established. With our current knowledge it cannot be excluded that hyperhomocysteinemia represents a risk marker rather than a causal risk factor. Assuming that increased plasma homocysteine concentrations had already been proven to be a causal risk factor for RVO, it would be nonetheless rather controversial to treat every patient homozygous for the MTHFR C677T mutation with homocysteine-lowering vitamins, regardless of the actual plasma homocysteine level. M. WEGER, MD, O. STANGER, MD W. RENNER, PHD O. SCHMUT, PHD A. HAAS, MD Graz, Austria References 1. Marcucci R, Bertini L, Giusti B, et al. Thrombophilic risk factors in patients with central retinal vein occlusion. Thromb Haemost 2001;86:772– 6. 2. Cahill M, Karabatzaki M, Meleady R, et al. Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease. Br J Ophthalmol 2000;84:154 –7. 3. Larsson J, Hultberg B, Hillarp A. Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand 2000;78:340 –3. 4. Cahill M, Karabatzaki M, Donoghue C, et al. Thermolabile MTHFR genotype and retinal vascular occlusive disease. Br J Ophthalmol 2001;85:88 –90. 5. Loewenstein A, Goldstein M, Winder A, et al. Retinal vein occlusion associated with methylenetetrahydrofolate reductase mutation. Ophthalmology 1999;106:1817–20. 6. Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C3 T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288:2023–31.
Balloon Catheter Dilatation Dear Editor: In the article by Tao et al1 on the “success of primary and secondary balloon catheter dilatation for congenital nasolacrimal duct obstruction,” there was a success rate of 75.9% in patients older than 24 months within the primary group. This result is similar to the success rate achieved with simple primary probing of the lacrimal system in children of this age group, as reported by some studies.2,3 Therefore, any recommendations made should be based on comparing the cost-effectiveness of primary balloon catheter dilatation versus primary probing.
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Hyperhomocysteinemia and BRVO Dear Editor: The article by Weger et al1 deals with the apparent Caucasian methylenetetrahydrofolate reductase (MTHFR) genotype data. The odds ratio for MTHFR 677CT/CC of 0.81 (as shown in their Table 3) was rather low. We analyzed 18 patients with branch retinal vein occlusion of AfricanAmerican (AA) ancestry from our eye clinic for the MTHFR C677T polymorphism and found that 6 patients were of the 677CT genotype, 0 of the 677TT genotype, and 12 of the 677CC genotype, giving a 677CT heterozygosity of 33%. However, when we analyzed 1472 AA control infants, we found 246 with the 677CT genotype, 20 with the 677TT genotype, and 1206 with the 677CC genotype, giving a 677CT heterozygosity of 16.7%. Thus, the 677CT genotype frequency in our AA patients was twice that found in the controls. Although our data were not statistically significant, probably due to a small sample size, nonetheless the odds ratio was 2.4, with a 95% confidence interval of 0.81–7.1, a chi-square value of 2.31, and a P value of 0.12. Based on our observations, we feel that there was a trend of increasing 677CT heterozygosity in the branch retinal vein occlusion patients relative to controls, at least in the AA ethnicity, the significance of which remains to be elucidated. Could the polymorphism relationship with branch retinal vein occlusion be ethno-specific? We are not sure because our MTHFR polymorphism data were too sparse to report from the Caucasian ethnicity. Larger data sets from both AA and Caucasian ethnicities would resolve the issue. If the relationship exists, we feel, a simple therapeutic folate regimen could alleviate the ocular vascular occlusions, at least in the AA community. KRISHNA YANAMANDRA, PHD, FACMG THEODORE F. THURMON, MD, FACMG JOSEPH A. BOCCHINI, JR, MD LAKSHMAN M. KOORAGAYALA, MD Shreveport, Louisiana Reference 1. Weger M, Stanger O, Deutschmann H, et al. Hyperhomocysteinemia, but not methylenetetrahydrofolate reductase C677T mutation, as a risk factor in branch retinal vein occlusion. Ophthalmology 2002;109:1105–9.
Author reply Dear Editor: We thank Dr Yanamandra and colleagues for their interest in our article. Recent studies have suggested hyperhomocysteinemia as a novel risk factor for retinal vein occlusion (RVO).1,2 Yet other investigators were unable to confirm these findings, resulting in an ongoing debate over the precise role of homocysteine in the pathogenesis of RVO.2,3 Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been shown to increase
plasma homocysteine levels, especially in the presence of suboptimal plasma folate levels. Previous studies focusing on the role of the MTHFR C677T mutation in RVO have yielded conflicting results.1,3–5 This, however, might reflect a considerable heterogeneity in the genotype distribution of the MTHFR C677T mutation among different populations.6 Study outcomes thus should be compared cautiously, especially if the number of study participants is small. Even if increased plasma homocysteine concentrations had consistently been found to be associated with RVO, a causal role and the potential benefits of lowering plasma homocysteine levels would still have to be established. With our current knowledge it cannot be excluded that hyperhomocysteinemia represents a risk marker rather than a causal risk factor. Assuming that increased plasma homocysteine concentrations had already been proven to be a causal risk factor for RVO, it would be nonetheless rather controversial to treat every patient homozygous for the MTHFR C677T mutation with homocysteine-lowering vitamins, regardless of the actual plasma homocysteine level. M. WEGER, MD, O. STANGER, MD W. RENNER, PHD O. SCHMUT, PHD A. HAAS, MD Graz, Austria References 1. Marcucci R, Bertini L, Giusti B, et al. Thrombophilic risk factors in patients with central retinal vein occlusion. Thromb Haemost 2001;86:772– 6. 2. Cahill M, Karabatzaki M, Meleady R, et al. Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease. Br J Ophthalmol 2000;84:154 –7. 3. Larsson J, Hultberg B, Hillarp A. Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand 2000;78:340 –3. 4. Cahill M, Karabatzaki M, Donoghue C, et al. Thermolabile MTHFR genotype and retinal vascular occlusive disease. Br J Ophthalmol 2001;85:88 –90. 5. Loewenstein A, Goldstein M, Winder A, et al. Retinal vein occlusion associated with methylenetetrahydrofolate reductase mutation. Ophthalmology 1999;106:1817–20. 6. Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C3 T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288:2023–31.
Balloon Catheter Dilatation Dear Editor: In the article by Tao et al1 on the “success of primary and secondary balloon catheter dilatation for congenital nasolacrimal duct obstruction,” there was a success rate of 75.9% in patients older than 24 months within the primary group. This result is similar to the success rate achieved with simple primary probing of the lacrimal system in children of this age group, as reported by some studies.2,3 Therefore, any recommendations made should be based on comparing the cost-effectiveness of primary balloon catheter dilatation versus primary probing.
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