Ocular disorders as the prevailing manifestations of antiphospholipid syndrome: a case series

Introduction: Antiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome. Case presentation: All the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuroophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them. Conclusion: Due to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization. © 2009 Tsironi et al; licensee BioMed Central Ltd

Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

Purpose: To investigate possible genetic associations of matrix metalloproteinase-1 (MMP1) and MMP3 gene polymorphisms with exfoliation syndrome (XFS) with (XFS/+G) and without (XFS/-G) glaucoma in a cohort of Greek patients. Methods: A total of 182 unrelated Greek patients with XFS, including 92 patients with XFS/+G, and 214 unrelated age- and gender-matched controls were enrolled in the study. MMP1-1607 1G/2G (rs1799750) and MMP3-1171 5A/6A (rs3025058) polymorphisms were determined using standard PCR/restriction fragment length polymorphism methods. Differences in allele and genotype distributions were analyzed using logistic regression. Results: The distribution of genotypes and alleles in MMP1 and MMP3 polymorphisms was not significantly different between cases with exfoliation syndrome, with or without glaucoma, and controls. However, the allele contrast for the MMP1 variant showed a trend for a significant association with XFS/-G (Odds Ratio=1.47 [1.03-2.10]), since after correction for multiple comparisons, this association was no longer statistically significant. Conclusions: Our study provided some evidence of a possible role of the MMP1 variant in the development of exfoliation syndrome in Greek patients

Plasminogen Activator Inhibitor Type-1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetes Mellitus Type 2 and Diabetic Retinopathy

<p><i>Background</i>: There is accumulating evidence for genetic susceptibility to the development of diabetic retinopathy (DR). The role of plasminogen activator inhibitor-1 (PAI-1) in DR risk remains controversial.</p> <p><i>Objective</i>: The present study was designed to investigate possible influence of PAI-1 gene region polymorphisms on the risk of DR and on the risk of developing DR early vs late in the course of type 2 diabetes mellitus (T2DM).</p> <p><i>Methods</i>: A total of 138 patients with DR, 107 patients with T2DM without DR, and 315 healthy controls were recruited. To cover the majority of the genetic variability across the extended region of PAI-1 gene, five tag single-nucleotide polymorphisms (SNPs) from the HapMap using a pairwise approach and an <i>r</i>² ≥ 0.8 and a minor allele frequency (MAF) of >0.05 were identified. Using logistic regression analyses, tag SNPs and haplotypes were tested for associations with DR risk and risk of DR development early or late in the course of T2DM. The generalized odds ratio (OR_G) was calculated to estimate the mutational load effect on DR development among all participants. Corrections for multiple comparisons were carried out (<i>p</i>-value < 0.01).</p> <p><i>Results</i>: A significant effect of rs2070682 on the risk of early DR onset was found in the codominant model of inheritance [odds ratio, OR (95% confidence interval, CI): 5.04 (1.47–17.28), <i>p</i> = 0.018]. However, this association marginally did not survive multiple testing corrections. No other significant association between PAI-1 tag-SNPs and haplotypes was revealed. Furthermore, no significant mutational load effect of PAI-1 tag SNPs on the risk of DR development in T2DM course was found.</p> <p><i>Conclusions</i>: In conclusion, the present study does not provide any strong evidence that <i>PAI-1</i> gene variants are implicated in the risk of DR or the development of DR during T2DM course.</p

The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis

The association between retincipathy in type 2 diabetes [diabetic retinopathy (DR)] and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in several case-control studies. These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of developing DR whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DR was conducted. Four out of five identified studies included populations of East Asian descent, and only one involved samples from European descent (Caucasians). Overall, the meta-analysis suggested large heterogeneity between studies (p = 0.08, I-2 = 52%) and marginal association between C677T transition and the risk of developing DR: random effects odds ratio (OR) = 1.39 [95% Cl (1.05, 1.83)]. The sensitivity analysis [exclusion of one East Asian study with the controls not in Hardy-Weinberg equilibrium (HWE)] showed no heterogeneity (p = 0.25, I-2 27%) and no significant association: fixed effects OR 1.22 [95% CI (0.99, 1.51)] and random effects OR = 1.24 [95% CI (0.96, 1.60)]. The sub-group analysis for the East Asian population produced a significant association: fixed effects OR = 1.48 [95% CI (1.20, 1.83)] and random effects OR = 1.52 [95% CI (1.14, 2.03)]. However, sensitivity analysis in East Asians revealed that the association is marginal: fixed effects OR = 1.33 [95% CI (1.04, 1.70)] and random effects OR = 1.36 [95% CI (1.01, 1.83)]. There is a source of bias in the selected studies: the largest studies failed to show association while the smallest study claimed an association. The above findings reinforce the need for larger and more rigourous studies in this area

Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach

To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology. © 2009 Elsevier Ltd