Genetic polymorphisms associated with the prevalence of retinal vein occlusion in a Greek population.

PURPOSE: To investigate possible associations of single-nucleotide polymorphisms (SNPs) from five genes with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). METHODS: A total of 69 patients with retinal vein occlusion-RVO (24 with BRVO and 45 with CRVO), and 82 controls, were enrolled in this study. All subjects were screened for hypertension, diabetes mellitus, hyperlipidemia, glaucoma, anticoagulant medication, smoking status and history of stroke. The genotyping of AGTR1-A1166C, adiponectin + 276 G/T, MMP2-1306C/T, Gpla/lla-C807T/G873A and VKORC1-G1639A polymorphisms was performed using restriction fragment length polymorphism or allele-specific polymerase chain reaction. RESULTS: The percentage of the AGTR1-A1166C C allele carriers and Gpla/lla-C807T/G873A T/A carriers was significantly higher in the CRVO patients than in the controls (P = 0.00001 and P = 0.0004, respectively). At the multiple logistic regression analysis, the AGTR1-A1166C C allele carrier status and the Gpla/lla-C807T/G873A T/A allele carrier status were found to be associated with an increased risk of CRVO. Moreover, adiponectin + 276 G/T T allele carriers had a significantly increased risk of RVO in subjects ≥ 75 years old. There was no significant difference between the BRVO patients and controls concerning the genotype or the allele frequency distributions of these SNPs. The genotype distributions or allelic frequencies of the other evaluated polymorphisms did not significantly differ between the patients with RVO and the control subjects. CONCLUSIONS: AGTR1 A1166C and Gpla/lla C807T/G873A polymorphisms are likely to be risk factors for CRVO. Adiponectin + 276 G/T SNP is likely to predispose to RVO in older subjects.

Mitochondrial Membrane Dynamics and Inherited Optic Neuropathies.

Inherited optic neuropathies are a genetically diverse group of disorders mainly characterized by visual loss and optic atrophy. Since the first recognition of Leber's hereditary optic neuropathy, several genetic defects altering primary mitochondrial respiration have been proposed to contribute to the development of syndromic and non-syndromic optic neuropathies. Moreover, the genomics and imaging revolution in the past decade has increased diagnostic efficiency and accuracy, allowing recognition of a link between mitochondrial dynamics machinery and a broad range of inherited neurodegenerative diseases involving the optic nerve. Mutations of novel genes modifying mainly the balance between mitochondrial fusion and fission have been shown to lead to overlapping clinical phenotypes ranging from isolated optic atrophy to severe, sometimes lethal multisystem disorders, and are reviewed herein. Given the particular vulnerability of retinal ganglion cells to mitochondrial dysfunction, the accessibility of the eye as a part of the central nervous system and improvements in technical imaging concerning assessment of the retinal nerve fiber layer, optic nerve evaluation becomes critical - even in asymptomatic patients - for correct diagnosis, understanding and early treatment of these complex and enigmatic clinical entities.

Immunohistochemical Study of Vasculogenic Mimicry and Angiogenesis in Melanocytic Tumors of the Eye and the Periocular Area.

BACKGROUND/AIM: The ability of a tumor to grow requires a sufficient blood supply. Microvascular density is considered the standard for assessing the neovasculature. Tumor cell vasculogenic mimicry refers to the formation of tumor cell-lined vessels that contribute to tumor neovascularization. The aim of the present work was to study angiogenesis and vasculogenic mimicry in benign and malignant melanocytic tumors of the eye and the periocular region. PATIENTS AND METHODS: Histological sections from 118 patients were studied. Eighty-eight of the patients had nevi while the remaining 30 had malignant melanomas. Microvascular density was assessed by using antibodies against the endothelial cell markers CD31 and CD34. Vascular-like channels between neoplastic cells, that were not lined by endothelial cells and thus were negative for CD31 and CD34, represented areas of vasculogenic mimicry. RESULTS: Angiogenesis was more pronounced in melanomas compared to melanocytic nevi and was increased in melanomas with high mitotic index and/or epithelioid cell preponderance compared to melanomas with low mitotic index and/or spindle cell predominance. Vasculogenic mimicry was observed in many melanomas, while it was evident in the minority of benign nevi as well. CONCLUSION: The existence of vasculogenic mimicry in benign nevi might have prognostic implications.

Natural Compounds and Neuroprotection: Mechanisms of Action and Novel Delivery Systems.

Neurodegeneration characterizes pathologic conditions, ranging from Alzheimer's disease to glaucoma, with devastating social and economic effects. It is a complex process implicating a series of molecular and cellular events, such as oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity and inflammation. Natural compounds, because of their broad spectrum of pharmacological and biological activities, could be possible candidates for the management of such multifactorial morbidities. However, their therapeutic potential against neurodegenerative diseases has been hampered by their poor bioavailability and subsequent insufficient delivery to the brain. This article provides an overview of the molecular mechanisms through which natural compounds exert their neuroprotective effects, as well as the development of novel natural compound-loaded delivery systems that could improve their neuroavailability.

Vasculogenic mimicry: lessons from melanocytic tumors.

Tumor cell vasculogenic mimicry refers to the formation of tumor cell-lined vessels that contribute to tumor neovascularization and nutrient and oxygen supply. These tumor cells express many endothelial and stem cell markers, resulting in them having a unique phenotype. This phenomenon is observed in a variety of neoplasms, such as glioblastomas and sarcomas, as well as breast, ovarian, liver and lung carcinomas. It is also evident in melanocytic lesions, regardless of their benign or malignant nature. The biochemical and molecular events that regulate vasculogenic mimicry provide opportunities for development of novel forms of tumor-targeted treatments. Furthermore, the presence of this process in a tumor might have prognostic implications.

Thrombophilic risk factors in the pathogenesis of non-arteritic anterior ischemic optic neuropathy patients.

BACKGROUND: Non-arteritic anterior ischemic optic neuropathy (N-AION) is caused by acute ischemic infarction of the optic nerve head, supplied by the posterior ciliary arteries. Thrombophilia is the tendency/predisposition to vascular thromboses of arteries and veins, and the existence of thrombophilic risk factors leads to blood hypercoagulability and potentially increased risk for thromboses. OBJECTIVES: To investigate whether there is an association between N-AION and a wide spectrum of thrombophilic risk factors. PATIENTS AND METHODS: Seventy-seven consecutive cases of confirmed N-AION and 60 age- and sex-matched consecutive controls constituted the study group. Fibrinogen levels, deficiency of proteins C, S, ATIII, lupus anticoagulant, activated protein C resistance, factor V Leiden, factor V H1299R, factor II G20210A, MTHFR C677T, MTHFR A1298C, GPIIIa A1/A2, and ACE I/D polymorphisms were analysed. RESULTS: Statistical analysis of the plasma proteins in our study demonstrated that the only significant difference was the one concerning protein S levels. In particular, the mean value for N-AION patients was 78.8% +/- 21.2, and for the control group the mean value was 88% +/- 21.2 (p = 0.013). Despite the above-mentioned result, there was not any statistical difference between the two subgroups regarding actual protein S deficiency, as 9/77 (11.7%) patients and 4/60 (6.7%) controls had protein S levels below 60% (p = 0.32). In our study sample, homozygosity for MTHFR C677T polymorphism in the study group as a whole, and the presence of at least one A2 allele of GPIIIa in the subgroup of male patients as compared to healthy male controls, proved to be the most significant thrombophilic risk factors, with odds ratios of 16.78 (95% C.I 0.96-294.42, p = 0.054) and 4.6 (95% C.I 1.52-13.88, p = 0.007) respectively. CONCLUSION: Screening for these polymorphisms would probably constitute a valuable procedure in N-AION patients, as they may have an important contribution to the pathogenesis of the disease.

Central corneal thickness in subjects with glaucoma and in normal individuals (with or without pseudoexfoliation syndrome).

OBJECTIVE: The evaluation of central corneal thickness (CCT) in subjects with pesudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and in normotensive individuals with or without pseudoexfoliation syndrome (PXS). STUDY DESIGN/PATIENTS AND METHODS: CCT was evaluated with ultrasound pachymetry in a total of 179 individuals: 32 had bilateral PEXG, 55 had bilateral POAG, 35 had PXS, and 57 were healthy individuals without PXS. RESULTS: CCT in PEXG eyes (526.00 +/- 34.30 mum) was significantly thinner compared to POAG eyes (549.36 +/- 39.3 mum) (P = 0.027) and normal control eyes with (550.64 +/- 39.0 mum) or without PXS (547.36 +/- 33.1 mum), (P = 0.039 and 0.048 respectively). No statistically significant difference was found comparing CCT values of POAG eyes to control group eyes. CONCLUSION: The evaluation of CCT is necessary in all patients with glaucoma and especially in those with PEXG due to the thinner cornea and the risk of underestimation of intraocular pressure.

Comparison of one-site versus two-site phacotrabeculectomy without the use of antimetabolites intraoperatively in patients with pseudoexfoliation glaucoma and primary open-angle glaucoma.

PURPOSE: The comparison of one-site versus two-site phacotrabeculectomy in patients with pseudoexfoliation glaucoma (PEXG) and primary open-angle glaucoma (POAG), with respect to intraocular pressure (IOP), antiglaucomatous medication (AM) requirements and visual acuity (VA). METHODS: Forty-seven patients (eyes) with cataract and POAG and 46 sex- and age-matched patients with cataract and PEXG were randomized to one- or two-site phacotrabeculectomy and reviewed with a follow-up at three years. RESULTS: Mean preoperative IOP was 22.04 +/- 2.27 mmHg and 22.92 +/- 2.35 mmHg in POAG and PEXG groups (p > 0.05) using a mean of 2.76 +/- 0.74, 2.74 +/- 0.69 AM, respectively (p > 0.05). After three years of follow-up, the mean IOP was 15.04 +/- 1.57 mmHg in the one-site, 15.04 +/- 1.99 mmHg in the two-site group with POAG, 15 +/- 1.8 mmHg in the one-site, 15.32 +/- 1.31 mmHg in the two-site group with PEXG, using a mean of 0.68 +/- 0.69, 0.84 +/- 0.75, 0.96 +/- 0.67, and 0.8 +/- 0.62 AM, respectively. Mean IOP and AM postoperatively were significantly less compared to preoperatively for each group (p < 0.05). No difference was observed in mean IOP and AM between the four groups at three years postoperatively (p > 0.05). VA improved similarly in four groups at the three-year follow-up (p < 0.05). Intraoperative, postoperative complications, and need for 5-fluorouracil injections were similar between the surgical groups. CONCLUSION: One-site and two-site phacotrabeculectomy without the use of antimetabolites intraoperatively were similarly safe and effective in IOP control over a three-year follow-up period in patients with POAG and PEXG.

Comparative results of central corneal thickness measurements in primary open-angle glaucoma, pseudoexfoliation glaucoma, and ocular hypertension.

BACKGROUND AND OBJECTIVE: As clinical measurements of corneal thickness have become widely available, several studies found a positive correlation between central corneal thickness and applanation tonometry measurements. This study evaluated central corneal thickness in different types of glaucoma. PATIENTS AND METHODS: An observational cross-sectional study assessed central corneal thickness using a specular microscope in the following groups of patients: 60 eyes with primary open-angle glaucoma, 50 eyes with pseudoexfoliation glaucoma, 50 eyes with ocular hypertension, and 60 eyes without glaucoma or ocular hypertension (control group). RESULTS: Central corneal thickness was significantly thinner in cases with pseudoexfoliation glaucoma (P < .0001) and significantly thicker in cases with ocular hypertension (P< .0001). CONCLUSIONS: These results agree with the literature, strengthening the position that central corneal thickness varies in different types of glaucoma and, therefore, is a parameter that should be taken under consideration, especially when evaluating cases of pseudoexfoliative glaucoma and ocular hypertension.

Neurological manifestations of connective tissue diseases mimicking multiple sclerosis.

The objective of the study was to analyze retrospectively the clinical, laboratory and imaging findings of multiple sclerosis (MS), such as the manifestations in a cohort of 132 patients referred to the neurology in and outpatient clinic. The proposed clinical and laboratory diagnostic criteria for MS and connective tissue disorders were systematically assessed in 132 consecutive patients. Cerebrospinal fluid serology and brain or spinal cord MRI were studied in all cases. In patients suspected for connective tissue disorder, schirmer test, rose bengal staining and biopsy of minor salivary glands were performed. A total of 115 (87%) patients were diagnosed to have definite MS, while 17 (13%) were diagnosed to have connective tissue disorder. Positive neurological and MRI findings were observed in both groups. The majority of patients with connective tissue disorder demonstrated extra-neurological manifestations like Raynaud's phenomenon, arthritis, livedo reticularis, purpura and presence of multiple autoantibodies in their sera. All patients with MS should be screened systematically for connective tissue disorder. In the absence of pathognomonic clinical and laboratory findings, the diagnosis of MS is a diagnosis of exclusion.

Psychiatric manifestations and personality traits associated with compliance with glaucoma treatment.

OBJECTIVE: The aim of this study was to assess the impact of psychological distress and personality traits on self-rated compliance with glaucoma treatment. METHODS: One hundred patients with primary open-angle glaucoma participated in the study. General Health Questionnaire, Symptom Distress Checklist, Center for Epidemiological Studies Depression Scale, Defense Style Questionnaire, and Hostility and Direction of Hostility Questionnaire were used. RESULTS: Forty-two percent of patients with glaucoma classified as "noncompliers," those who omitted more than two doses per week. Noncompliers presented more severe symptoms of glaucoma. Depression was found to be associated with poor compliance, whereas adoption of immature defensive style further increased the risk for noncompliance with glaucoma treatment. CONCLUSIONS: Depression is associated with self-reported noncompliance with glaucoma treatment, whereas certain personality traits are involved in the increased risk for noncompliance. Further assessment of the depressive feelings by an ophthalmologist and treatment of depression as well as proper psychotherapeutic approaches for maladaptive personality features could be an essential strategy to diminish compliance problems.