Mark Cahill

Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease

BACKGROUND/AIMS A moderately elevated plasma concentration of the sulphur amino acid homocysteine is an independent risk factor for atherosclerotic vascular disease. Many of the risk factors associated with coronary, cerebral, and peripheral atherosclerotic vascular disease are common to retinal vascular occlusive disease but it is unclear whether elevated plasma concentrations of homocysteine are also associated with such disease. This study assessed the relation between retinal vascular occlusive disease and elevated levels of plasma total homocysteine (tHcy). METHODS A retrospective case-control study involving hospital based controls and cases with retinal artery, central retinal vein (including hemiretinal vein), and branch retinal vein occlusions was performed. The relation between elevated tHcy, defined as a level greater than or equal to 12 μmol/l and risk of retinal vascular occlusive disease was examined. RESULTS 87 cases of retinal vascular occlusive disease including 26 cases of retinal artery occlusion, 40 cases with central retinal vein occlusion, and 21 cases of branch retinal vein occlusion were compared with 87 age matched controls. Mean tHcy levels were higher in all disease groups and this difference was significant in patients with retinal artery occlusions (p= 0.032) and patients with central retinal vein occlusion (p=0.0001). When adjusted for known cardiovascular risk factors, tHcy was an independent risk factor for retinal vascular occlusive disease (OR 2.85 (95% CI 1.43–5.68)). CONCLUSIONS Elevated tHcy is an independent risk factor for retinal vascular occlusive disease. Assessment of tHcy may be important in the investigation and management of patients with retinal vascular occlusive disease.

Ocular adnexal lymphoma—comparison of MALT lymphoma with other histological types

AIMS To correlate histological features of ocular adnexal lymphoma using the revised European American lymphoma classification (REAL), with stage of disease at presentation, treatment modalities, and patient outcome. MALT lymphoma defines an extranodal marginal zone B cell lymphoma as outlined in the REAL classification. Comparison groups of patients included those with primary ocular adnexal MALT lymphoma versus primary ocular adnexal lymphomas of other types, MALT lymphoma versus non-MALT lymphomas (primary and secondary), and primary ocular adnexal lymphoma (MALT lymphomas and other types) versus secondary ocular adnexal lymphomas. METHODS A retrospective review of the National Ophthalmic Pathology Laboratory records identified 20 cases of ocular adnexal lymphoma over a 10 year period which were reclassified using appropriate immunohistochemical stains. Patients’ medical records were examined for data including stage of the disease at presentation, mode of treatment, and patient outcome. RESULTS Among the 20 cases identified 14 had primary ocular adnexal lymphomas. 10 of the primary lymphomas had histological features of MALT lymphoma. One case was a primary ocular adnexal T cell lymphoma, one a follicular centre, follicular B cell lymphoma, and two were large cell B cell lymphomas. Six cases had systemic disease, four large B cell, one follicular centre, follicular B cell, and one mantle cell. A significantly higher proportion of patients with MALT lymphomas had early disease (p = 0.005), initially required local treatment (p = 0.005) and were alive at last follow up (p = 0.001) than those without. Two patients with MALT lymphoma had recurrence of lymphoma which responded to further treatment. CONCLUSIONS Patients with primary ocular adnexal MALT lymphomas present with localised disease requiring local treatment and have a better outcome compared with patients with other types. As a small percentage of these tumours recur, patients should be followed up indefinitely.

Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism, and Risk of Retinal Vein Occlusion: A Meta-analysis

OBJECTIVE To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease. DESIGN Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published. PARTICIPANTS AND/OR CONTROLS RVO patients and controls. METHODS Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods. MAIN OUTCOME MEASURES tHcy concentrations and MTHFR genotype. RESULTS There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 micromol/L (95% confidence interval [CI], 1.8-3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P<0.001, I(2) = 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84-1.71), but again marked heterogeneity (P = 0.004, I(2) = 53%) was observed. CONCLUSIONS There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Thermolabile MTHFR genotype and retinal vascular occlusive disease

BACKGROUND Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined. METHODS A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined. RESULTS 87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients. CONCLUSIONS The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.

Pilomatrix carcinoma of the eyelid.

PURPOSE To report a case of a recurring mass with an unusual origin on the eyelid of a 34-year-old man. METHOD Case report. RESULT Histology demonstrated that the mass was a pilomatrix carcinoma. CONCLUSION An atypical mass with unusual symptoms or signs needs definitive treatment and diagnostic confirmation with histology.

Ataxia and vision loss: flow cytometric diagnosis of primary central nervous system lymphoma

Approximately 20% of patients with primary central nervous system lymphoma will have eye involvement, which often precedes diagnosis by a number of months.1–4 The diagnosis of intraocular and/or CNS lymphoma depends on histological evidence in tissue obtained from a CNS biopsy or cytological demonstration of malignant cells in the vitreous or cerebrospinal fluid (CSF).4 Cytological differentiation of reactive lymphoid cells from well differentiated lymphoma using morphological characteristics depends on observer skill and the preservation of adequate numbers of cells.5 Immunocytochemical staining of cell surface antigens assists in this differentiation and can detect cell population monoclonality, a common feature of large B cell lymphomas.5 Cytofluorography or flow cytometry is a semiautomated method of immunocytochemistry which has some advantages over slide based immunocytochemistry including objective and quantitative data on cell surface markers.6,7 We present a patient with ataxia and vision loss who was diagnosed with primary CNS lymphoma using cytofluorographic analysis of a vitreous biopsy specimen. A 53 year old woman was diagnosed with bilateral panuveitis. Best …

Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population

Background/aims Age-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland. Methods Prevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression. Results Older age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline. Conclusions The prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.