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Panagiotis Kousiouris,1,&ast; Nikolaos Gouliopoulos,2,&ast; Anastasia Kourtesa,1,&ast; Georgios S Dimtsas,1 Klio Chatzistefanou,1 Nikolaos Bouratzis,2 Maria Kantzanou,3 Marilita M Moschos1 1 1st Department of Ophthalmology, University of Athens Medical School, G. Gennimatas Hospital, Athens, Greece; 2 2nd Department of Ophthalmology, University of Athens Medical School, Attikon Hospital, Athens, Greece; 3Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece&ast;These authors contributed equally to this workCorrespondence: Marilita M Moschos, 1st Department of Ophthalmology, University of Athens Medical School, G. Gennimatas Hospital, 154 Leof. Mesogeion, Athens, 115 27, Greece, Tel +30 6944887319, Email moschosmarilita@yahoo.frPurpose: To present the demographic and social characteristics of patients with ocular foreign bodies (OFB), who visit the Ophthalmological Outpatient Department of a tertiary hospital in Athens, Greece.Patients and Methods: During the period January-March 2019, 5181 patients presented to the Ophthalmological Outpatient Department of our hospital, and 543 of them were diagnosed with an ocular foreign body. Moreover, 106 of them were interviewed about their demographic and social factors, regarding among others data about their occupation, level of education, nationality, family, and insurance status.Results: The patients with ocular foreign bodies were significantly younger compared to the rest of the examined patients (49.5± 13.9 vs 56.3± 17 years, p< 0.001). Moreover, the ocular foreign bodies were more frequent in men compared to women (15.5% vs 5.0%, p< 0.001) and in non-Greek patients (23.7% vs 9.2%, p< 0.001). Regarding the social characteristics of the patients with ocular foreign bodies, we found that the majority of them were married, employed, insured, while their educational status was middle and high school. Furthermore, the vast majority of the patients practiced manual professions (73.1% of them).Conclusion: We documented that the introduction of an ocular foreign body is frequently encountered in the Outpatient Department of our tertiary hospital in Athens, Greece. We also demonstrated that these patients are younger, while they are more frequently men, of non-Greek origin, with an educational status of middle and high school, and their occupation is associated with manual labour.Keywords: ocular foreign body, ocular trauma, demographic characteristics, social characteristics

Panagiotis Kousiouris,1,&ast; Olga Klavdianou,1,&ast; Konstantinos AA Douglas,1 Nikolaos Gouliopoulos,2 Klio Chatzistefanou,1 Maria Kantzanou,3 Georgios S Dimtsas,1 Marilita M Moschos1 1 1st Department of Ophthalmology, National and Kapodistrian University of Athens, “G. Gennimatas” General Hospital, Athens, Greece; 2 2nd Department of Ophthalmology, National and Kapodistrian University of Athens, “Attikon” General Hospital, Athens, Greece; 3Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece&ast;These authors contributed equally to this workCorrespondence: Marilita M Moschos 1st Department of Ophthalmology, National and Kapodistrian University of Athens, “G. Gennimatas” General Hospital, Leof. Mesogeion 154, Athens, 115 27, GreeceTel +30 6944887319Email moschosmarilita@yahoo.frAbstract: Globe injury is a serious worldwide public health issue frequently leading to permanent vision impairment. The plethora of different types of globe injuries is classified into categories, including open and closed globe injuries. Globe injury occurs mainly in the workplace and at home, affecting predominantly middle-aged working men. Socioeconomic status (SES) is defined by income level, educational attainment, and employment status. Low socioeconomic status has been associated with a higher incidence of globe injury and can be utilized to identify at-risk populations. For managing open and closed globe injuries, different strategies are applied and the implementation of adequate globe injury prevention measures is needed for reducing the occurrence of globe injury. The following article aims to provide an overview of globe injury characteristics and their correlation with socioeconomic status and to highlight the significance of considering SES as a variable in globe injury prevention.Keywords: eye injuries, occupational injuries, social class, educational status

OBJECTIVE: Diabetic retinopathy is the leading cause of irreversible blindness in the western world, among the working-age people. Its exact pathogenesis, however, remains obscure. Systemic inflammation is regarded to play a significant role in diabetes by contributing, among others, to the development of diabetic retinopathy. This review focuses on the possible involvement of the systemic inflammatory markers in the pathogenesis of diabetic retinopathy. MATERIALS AND METHODS: We performed a systematic search of the literature of published papers until August 2017 using the PubMed search engine. RESULTS: We demonstrated that many systemic inflammatory markers contribute to the pathogenesis and progression of retinopathy, while we highlighted in several occasions their usefulness as a key tool in the monitoring of the disease progression and the treatment efficacy. CONCLUSIONS: To the best of our knowledge this is the first review in the literature that elaborates the possible association of serum inflammatory markers and diabetic retinopathy, a disease that may cause irreversible loss of vision. [ABSTRACT FROM AUTHOR]

Marilita M Moschos,1 Nikolaos S Gouliopoulos,1 Christos Kalogeropoulos2 1Laboratory of Electrophysiology, First Department of Ophthalmology, University of Athens, Athens, Greece; 2Department of Ophthalmology, University of Ioannina, Ioannina, Greece Purpose: Uveitis is the inflammation of the uveal tract, which usually also affects the retina and vitreous humor. The electrophysiological examination is an objective ocular examination that includes the electroretinogram, visual evoked potentials, the electrooculogram, the multifocal electroretinogram, and multifocal visual evoked potentials. Our aim is to review the literature of the use of the electrophysiological examination in cases of uveitis. Methods: We performed a systematic search of the literature of published papers until October 2012 using the PubMed search engine. The key terms that were used were “uveitis,” “electrophysiological examination”, “electroretinogram”, “visual evoked potentials”, “electro-oculogram”, “multifocal electroretinogram”, and “multifocal visual evoked potentials” in multiple combinations. To the best of our knowledge, this is the first review concerning the assessment of electrophysiology in uveitis. Results: Our search of the literature demonstrated that the electrophysiological examination, mainly by means of electroretinogram, multifocal electroretinogram, and visual evoked potentials, is performed in several cases of uveitis for many purposes, including diagnosis and monitoring of disease progression and treatment efficacy. The electrophysiological examination is more useful in patients with multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, birdshot chorioretinopathy, Vogt–Koyanagi–Harada disease, Adamantiades–Behçet disease, ocular syphilis, and Fuchs heterochromic cyclitis. Conclusion: This review summarizes the use of the electrophysiological examination in uveitic patients and underlines its value as a useful tool in the objective assessment and the monitoring of the disease. Keywords: uveitis, ERG, mfERG, VEP

Our aim was to assess whether systemic endothelial dysfunction, evaluated non-invasively by flow mediated dilation (FMD), is associated with diabetic macular edema (DME) and to determine if it is further impaired in patients with diffuse-DME. Consecutive patients ( n = 84) with type-2 diabetes mellitus (T2DM) and diabetic retinopathy were enrolled. DME was not present in 38 (non-DME) and present in 46 patients; 25 with focal and 21 with diffuse-DME. No differences were detected between DME and non-DME groups regarding the clinical and demographic characteristics, except for the age of T2DM initiation (lower in non-DME). FMD values were significantly impaired in DME compared with non-DME patients, even after adjustment for multiple covariates (3.56 ± 1.03 vs 4.57 ± 1.25%, P = .003). Among DME patients, no differences were found concerning the clinical and demographic data, while FMD levels were significantly lower in diffuse-DME patients, compared with the focal-DME ones, regardless of the impact several confounders (2.88 ± 0.65 vs 4.08 ± 0.95%, P = .002). It is noteworthy that FMD values of non-DME and focal-DME patients did not differ significantly (4.52 ± 1.24 vs 4.21 ± 1.06%, P = .307). Moreover, among DME patients, impaired FMD was an independent predictor of diffuse-DME (odds ratio: 0.06, 95% CI 0.01-0.47, P = .007)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the levels of anxiety and depression in patients with symptomatic vitreous floaters and to determine the possible correlations of psychological implications with the symptoms duration and possible improvement, the degree of posterior vitreous detachment, and the discomfort severity., Methods: Ninety patients complaining for floaters and fifty-seven age- and gender-matched healthy-control subjects were recruited. Every participant underwent a complete ophthalmological examination, including funduscopy and optical coherence tomography scans, while clinical and demographic data were also gathered. The Patient Health Questionnaire-9 (PHQ-9), the Zung Depression Inventory-Self-Rating Depression Scale (Zung SDS), and the Hospital Anxiety and Depression Scale (HADS) were completed by everyone., Results: Between the studied groups, no significant differences were detected regarding the clinical and demographic data (p > 0.05). The patients with floaters had significantly higher scores of PHQ-9, Zung SDS, HADS Anxiety, and HADS Depression (p < 0.001). After adjustment for several confounders, PHQ-9 (p = 0.041), Zung SDS (p = 0.003), and HADS Anxiety (p = 0.036) values remained significantly impaired. Among the patients, PHQ-9 and Zung SDS scores were significantly elevated in the patients with floaters duration less than 4 weeks (p < 0.05). Finally, anxiety and depression were significantly correlated with the symptoms duration and intensity, with the floater-associated discomfort, and with the stage of posterior vitreous detachment., Conclusion: Vitreous floaters have a negative impact on patients' psychological status, by the terms of enhanced depressive and anxiety levels. To the best of our knowledge, our study is the first in the literature to elaborate the aforementioned association, by assessing three different questionnaires simultaneously., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To present a case of a patient with bilateral wet age-related macular degeneration (AMD) who was unilaterally treated with intravitreal aflibercept injections (IAIs) and the disease status in the fellow eye ameliorated after an IAI., Methods: Retrospective case report., Results: A 72-year-old woman was diagnosed with wet and dry AMD in her right (OD) and left (OS) eye, respectively. In OD, treatment strategy comprised 3 monthly IAIs, followed by re-injections according-to-need, while optical coherence tomography (OCT) scans were performed before IAIs. One month after the second IAI, subretinal fluid developed in OS. One week later, an IAI was applied in OD; two days later the disease status in OS was assessed by fluorescein angiography and OCT. Surprisingly, in OS subretinal fluid completely resolved and fluorescein angiography did not detect leakage, highlighting the absence of an active choroidal neovascularization. The short interval between IAI and the resolution of exudative phenomena in the other eye is suggestive of a beneficial effect in the contralateral eye., Conclusion: Herein we showed that an IAI had an effect to the fellow untreated eye. Our observation is consistent with active aflibercept in the systemic circulation. To the best of our knowledge, no other report in literature has demonstrated this effect of aflibercept in wet AMD.

Aim: To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration (AMD)., Methods: Fifty naïve and previously untreated patients suffering from wet AMD, were randomly assigned in two subgroups of 25 patients each. All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept (IAIs) followed by injections "according to need", while in one group the patients also received daily two tablets of resveratrol oral supplement. Prior to treatment initiation, a complete ophthalmological examination, including best corrected visual acuity (BCVA) and contrast sensitivity evaluation, optical coherence tomography (OCT) scans, fundus autofluorescence (FAF), fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), was performed to every participant, while all of them completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, in order to assess their quality of life (QoL) status. The patients were assessed monthly for 1y with FAF, and OCT or OCTA; the main endpoints were the number IAIs, the changes in BCVA, in contrast sensitivity, and in patients' QoL status., Results: No significant differences were present between the groups regarding the baseline demographic and clinical data. Over the 12-month period, a similar number of IAIs was applied in both groups (4.52±1.00 vs 4.28±0.90, P =0.38), while the rest of the clinical data also did not differ significantly after the completion of the study period. However, for HADS Depression (11.88±2.51 vs 8.28±1.54, P <0.001) and HADS Anxiety (11.92±2.52 vs 7.76±1.51, P <0.001) questionnaires values, the score was significantly better in patients who received resveratrol supplements. Moreover, a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity (0.17±0.19 vs 0.35±0.24, P =0.005), HADS Depression (0.08±1.38 vs -3.88±1.48, P <0.001), and HADS Anxiety (0.36±1.98 vs -5.12±2.70, P <0.001) scores, in favour of the patients treated with resveratrol supplements., Conclusion: The resveratrol oral supplement is a complementary treatment in cases of wet AMD, highlighting its effectiveness in improving patients' QoL status., (International Journal of Ophthalmology Press.)

Purpose: To investigate whether a seasonal distribution of the frequency of exudative age-related macular degeneration (wet AMD) recurrences exists., Methods: In total, 129 eyes with 171 recurrences in patients suffering from wet AMD were included in the study. All the patients had been treated with intravitreal anti-VEGF injections according to Pro Re Nata treatment regimen. Recurrence was defined as the re-detection of sub-retinal fluid, intraretinal fluid, and/or sub-macular hemorrhage in optical coherence tomography scans, after at least two consecutive monthly examinations with a "dry" macula. The year was divided in three 4-month periods (zone A: June-September, zone B: October-January, and zone C: February-May) based on the weather conditions prevailing in each period. Mean temperature and hours of sunlight exposure were the main weather markers recorded., Results: Eighty-two recurrences (48%) occurred during the period June-September, 50 (29.2%) during the period October-January, and 39 (22.8%) during the period February-May (Chi-square = 17.5, p < 0.001). Among the groups, neither patients' age (78 ± 8 years A, 76 ± 7 years B, and 79 ± 8 years C, p = 0.15) nor gender status (40% men A, 36% men B, and 51% men C, p = 0.35) differed significantly. Mean temperature was 27.6 ± 1.8 °C, 15.1 ± 4.6 °C, and 16.5 ± 4.4 °C in zones A, B, and C, respectively. Hours (h) of sunlight exposure (average hours/month) were 344 ± 34 h, 188 ± 42 h, and 223 ± 57 h in zones A, B, and C., Conclusion: We demonstrated that the frequency of wet AMD recurrences is significantly elevated during the warmer months, possibly due to the higher levels of UV radiation and mean temperature. Further research is necessary to validate our findings., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Central serous chorioretinopathy (CSCR) is characterized by serous detachment of the central neurosensory retina and it is one of the most common retinal disorders. Various genetic polymorphisms have been associated with CSCR development., Methods: The aim of our study was to investigate the potential association between ARMS2 (rs10490924) and NR3C2 (rs2070951 and rs5522) genes polymorphisms and CSCR development in a well defined Greek cohort for the first time in literature. We enrolled, in our case-control study, 48 CSCR patients and 137 controls. The ARMS2 (rs10490924) and NR3C2 (rs2070951 and rs5522) genes polymorphisms were analyzed using Polymerase Chain Reaction (PCR) assays., Results: In our study, we found significant associations between ARMS2 rs10490924 and NR3C2 rs2070951 single nucleotide polymorphisms and CSCR development. Specifically, the GTrs10490924 genotype frequency of the ARMS2 gene was found to be significantly associated with risk of CSCR and T allele of rs10490924 ARMS2 gene was also found to increase risk for CSCR. The genotype frequency GC and CC of rs2070951 NR3C2 gene were observed more frequently in CSCR patients than controls and C allele of rs2070951 NR3C2 gene was also observed more frequently in CSCR patients than controls. Rs5522 of NR3C2 gene polymorphism was not found to be significantly associated with CSCR., Conclusion: Our findings showed, for the first time in a Greek population, that SNPs in the ARMS2 and NR3C2 genes are significantly associated with risk of CSCR. The results of this study support the involvement of extracellular matrix ( ARMS2 gene) and mineralocorticoid receptor (MR) in the pathogenesis of CSCR.

Background: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF., Methods: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to HF group., Results: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166-1.814, p = 0.019). Single-vessel coronary artery disease was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01)., Conclusions: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Purpose: To evaluate the possible associations between AGER (rs1051993, rs2070600) and ALDH2 (rs671) gene polymorphisms with nonproliferative (NPDR) and proliferative (PDR) diabetic retinopathy, in a well-defined Greek population., Materials: 66 NPDR patients and 57 PDR patients participated in our study, along with 156 age- and gender-matched healthy-control subjects (CL). All the participants underwent a complete ophthalmological examination, while clinical and demographic data were collected. Furthermore, they were genotyped for the studied polymorphisms., Results: No significant differences were detected among the studied groups regarding the participants' age and gender status. We found that the ALDH2 AA genotype was significantly more frequent in PDR patients than in CL ( p  = 0.014). Furthermore, between NPDR and PDR groups, the AGER rs1051993 GT and TT genotype frequencies were significantly elevated in PDR patients ( p  < 0.0001 and 0.04, respectively). Moreover, we demonstrated that the heterozygous GT genotype in DR patients is accompanied by 71.11 times higher risk of developing PDR (OR = 71.11: 95% CI- 4.14-1215.2), while the homozygous TT genotype is associated with 12.71 times elevated risk for PDR development (OR = 12.71: 95% CI- 0.63-254.1)., Conclusions: We documented that the ALDH2 AA and AGER rs1051993 GT and TT genotypes were observed significantly more frequently in PDR Greek diabetic patients. Our findings also support the genetic theory, suggesting that heritability is significantly implicated in the development of DR, providing additional evidence in the understanding of DR pathogenesis.

Purpose: To investigate whether eNOS T786C (rs2070744) and G894T (rs1799983) gene polymorphisms are associated with diabetic retinopathy in Greek diabetic patients., Materials: 271 patients with type-2 diabetes mellitus participated in our study; 130 suffered from diabetic retinopathy and 141 not. All the patients underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for rs2070744 and rs1799983 single nucleotide polymorphisms of eNOS gene., Results: Regarding the clinical and demographic data, no significant differences were detected between the studied groups, except for hemoglobin A1c levels and the frequency of insulin treatment (higher in patients with diabetic retinopathy). The frequency of rs1799983 GT genotype was significantly elevated in patients with diabetic retinopathy (55% vs. 40%, P  = 0.011) and was associated with a 2-fold increased risk of developing retinopathy (OR 1.92, 95% CI 1.16-3.17). Furthermore, we demonstrated that the aforementioned genotype was significantly and independently associated with increased odds for retinopathy onset in diabetic subjects (OR 2.23, 95% CI 1.28-3.90, P  = 0.005), regardless of the impact of other confounders., Conclusions: We documented that rs1799983 GT genotype could be recognized as an independent risk factor of retinopathy in Greek patients with type-2 diabetes mellitus, while no role for rs2070744 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk for diabetic retinopathy development.

Background: Several genetic polymorphisms have been identified as risk factors for diabetic retinopathy (DR) onset. The purpose of our study was to determine whether ADIPOQ rs1501299 and rs2241766 gene polymorphisms are associated with DR in a cohort of Greek diabetic patients., Materials and Methods: 218 patients with type-2 diabetes mellitus (T2DM) were included in the study; 109 suffered from DR and 109 not. All the participants underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene., Results: Between the studied groups, no significant differences were detected regarding the demographic and clinical data ( p > .05 for all), except for hemoglobin A1c levels and frequency of insulin treatment (higher in DR patients). We detected that the frequency of rs1501299 GT genotype was significantly elevated in DR patients (53% vs. 34%, p = .004) and was associated with a higher risk of developing retinopathy (OR 2.31, 95% CI 1.30-4.11). Furthermore, we demonstrated that the rs1501299 GT genotype was significantly and independently associated with increased odds for DR development in diabetic subjects (OR 2.68, 95% CI 1.38-5.21, p = .004), regardless of the impact of other known risk factors., Conclusions: We documented that rs1501299 GT genotype could be recognized as an independent risk factor of retinopathy in T2DM Greek patients, while no role for rs2241766 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk of DR development.

Purpose: To compare the 1-year outcomes of treat-and-extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy (PCV), by the means of visual acuity (VA), frequency of recurrence of polypoidal lesions and developed fibrosis, and the number of intravitreal injections, and thus to determine which one is preferable in the maintenance phase in PCV., Methods: In our prospective study, only naive and previously untreated PCV patients were included. Initially one session of photodynamic therapy (PDT) and three monthly intravitreal injections of 2.0 mg aflibercept (IAIs) were applied in 38 eyes. After this loading phase, they were re-examined and 30 PCV eyes with no exudative phenomena were included in the study. They were divided in two groups; in the first one (16 patients) the PRN treatment modality of IAIs was applied, while in the second one (14 patients) the treat-and-extend regimen was applied., Results: Over a 12-month period, VA significantly improved in treat-and-extend group (logMAR BCVA 0.41 ± 0.15 vs 0.57 ± 0.24 at baseline, p  = 0.044), while in the PRN group VA remained stable (logMAR BCVA 0.70 ± 0.36 vs 0.65 ± 0.18 at baseline, p  = 0.61). During the maintenance phase, the patients of treat-and-extend group did not encounter development/progression of fibrosis or any recurrent episodes, whereas the patients of PRN group had significantly more recurrent episodes (0 vs 1.37 ± 0.5, p  < 0.001) and the frequency of development/progression of fibrosis was significantly higher (0% vs 44%, p  = 0.02). However, the treat-and-extend treatment regimen was accompanied by significantly more administered IAIs (6 ± 0 vs 5.13 ± 1.08, p  = 0.006)., Conclusion: We highlighted the superiority of treat-and-extend regime with IAIs, which seems to yield better functional outcomes by preventing recurrence and subfoveal fibrosis, although a greater number of injections is required.

Background: The clustering of arterial stiffness with microvascular disease (MD) and their effects on the clinical outcome of patients with type 2 diabetes (T2D) remains not fully clarified., Methods: In a prospective study of 414 patients with T2D, we investigated the prognostic value of arterial stiffness and MD for clinical outcomes. Participants were assessed for the presence of MD (ie diabetic retinopathy, nephropathy and neuropathy) and arterial stiffness by pulse wave velocity (PWV) and followed-up for a median of 30 (range 1-60) months. The primary endpoint of the study was the composite endpoint of major adverse cardiovascular events, that is, cardiovascular and non-cardiovascular mortality and non-fatal myocardial infarction/stroke., Results: A total of 146 (35.3%) patients had evidence of MD at baseline. In cox regression models, MD and PWV were independently associated with the composite clinical endpoint; for MD hazard ratio (HR), 3.24, 95%CI, 1.10-9.54, P=.032, and for PWV HR, 1.20, 95%CI, 1.06-1.36, P=.004) after adjustment for traditional risk factors, and enhanced risk discrimination and reclassification. The subgroup of patients with MD and high PWV was associated with increased incidence of the composite clinical endpoint (20.9% vs 1.8% in those with no MD & low PWV, P=.001). Importantly, absence of MD at baseline was associated with no mortality events during the follow-up period. PWV at baseline was not associated with MD progression during follow-up., Conclusions: These findings support that screening for arterial stiffness and MD in the routine clinical assessment of patients with T2D may enhance prognostication and cardiovascular risk reclassification., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology. We enrolled 143 patients with stable HF of ischemic etiology and reduced left ventricular ejection fraction (LVEF) and 77 control subjects. Flow-mediated dilation (FMD) was used to evaluate endothelial function and pulse wave velocity (PWV) to assess arterial stiffness. Although there was no significant difference in baseline demographic characteristics, levels of sST2 were increased in HF compared to the control (15.8 (11.0, 21.8) ng/mL vs. 12.5 (10.4, 16.3) ng/mL; p < 0.001). In the HF group, there was a positive correlation of sST2 levels with age (rho = 0.22; p = 0.007) while there was no association of LVEF with sST2 (rho = -0.119; p = 0.17) nor with PWV (rho = 0.1; p = 0.23). Interestingly, sST2 was increased in NYHA III [20.0 (12.3, 25.7) ng/mL] compared to patients with NYHA II (15.0 (10.4, 18.2) ng/mL; p = 0.003) and inversely associated with FMD (rho = -0.44; p < 0.001) even after adjustment for possible confounders. In patients with chronic HF of ischemic etiology, sST2 levels are increased and are associated with functional capacity. There is an inverse association between FMD and sST2 levels, highlighting the interplay between the dysfunctional endothelium and HF pathophysiologic mechanisms.

Background/aim: Acceptance of corneas from donors with a malignancy remains controversial, especially for donors with hematological malignancy. The aim of our study was to examine, for the first time in literature, any structural differences in the integrity of the corneal grafts from donors who have received and from those who have not received chemotherapy., Materials and Methods: The immunohistochemical expression of CD44 was examined in 12 corneal grafts obtained from 8 donors. Three grafts were obtained from 2 donors who had received chemotherapy and the rest were obtained from 6 donors who had not received any kind of chemotherapy., Results: Epithelial cells expressed the CD44 molecule in all grafts of both groups. No CD44 expression was noticed on endothelial cells or in the stroma., Conclusion: Tumorigenesis and the consequent chemotherapy did not affect the structure and integrity of the corneal tissue in the examined samples. We suggest that corneal grafts from cancer donors are safe and functionally equals to grafts obtained from non-cancer donors., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Retinal vein occlusion (RVO) is a common retinal vascular lesion, and a leading cause of visual impairment. Patients with RVO have an increased risk for cardiovascular disease and share multiple common risk factors. In this study, we investigated the endothelial function and arterial stiffness of patients with RVO compared to healthy-control (CL) subjects. We enrolled 40 consecutive patients with RVO and 40 CL subjects. RVO was diagnosed by an ophthalmologist, endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery, and carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) of the radial artery were measured to evaluate arterial stiffness and reflected waves, respectively. No significant differences were detected between the studied groups in sex, age, presence of hypertension or dyslipidemia, body mass index, systolic and diastolic blood pressure levels, total cholesterol levels, and smoking habits ( p > 0.05 for all). However, patients with RVO had impaired FMD ( p = 0.002) and increased PWV ( p = 0.004), even after adjustment for several confounders. Both FMD and PWV were also significantly and independently associated with the development of RVO. Furthermore, a significant and positive correlation between PWV and systolic blood pressure existed only in the CL group. Therefore, we have shown that RVO is associated with significant endothelial dysfunction and increased arterial stiffness. Our results strengthen the vascular theory, according to which, systemic endothelial dysfunction and arteriosclerosis play a significant role in the pathogenesis of RVO.

Glaucoma is a progressive optic neuropathy resulting from retinal ganglion cells death; it represents one of the leading causes of irreversible blindness worldwide. Although, primary open angle glaucoma (POAG) is the most common type of the disease, the pathogenesis of POAG and the genetic factors contributing to disease development remain poorly understood. The aim of this study was to investigate whether the polymorphisms rs76481776 in miR182 gene and rs3217992 in cyclin-dependent kinase inhibitor-2B (CDKN2B) gene are risk factors for POAG in a series of patients of Greek origin. A case-control study was conducted including 120 patients with POAG and 113 unaffected healthy controls of Greek origin, surveyed for polymorphisms with potential correlation to POAG. DNA from each individual was tested for the miR182 rs76481776 and CDKN2B rs3217992 polymorphisms. Regarding the miR182 rs76481776 polymorphism, the T allele occurred with significantly higher frequency in POAG patients compared to controls (OR: 2.62, 95% CI: 1.56-4.39; p = 0.0002). The CDKN2B rs3217992 A allele frequency was found significantly increased in POAG patients compared to healthy individuals (OR: 1.72, 95% CI: 1.18-2.49; p = 0.005). Therefore, both rs76481776 polymorphism in miR182 gene and rs3217992 polymorphism in CDKN2B gene seem to be associated with the development of POAG in a Greek population. The carriers of the T allele of rs76481776 in miR182 and the carriers of the A allele of rs3217992 in CDKN2B have an increased risk of developing POAG., Competing Interests: The authors have declared that no competing interests exist.

PRéCIS:: Pseudoexfoliative glaucoma (PExG) patients present with not only endothelial dysfunction and arterial stiffness but also with a specific profile of circulating apoptotic endothelial microparticles which may be owing to the accumulation of pseudoexfoliative material in vessels walls., Purpose: PExG is characterized by the deposition of pseudoexfoliative material in several tissues and organs including in the cardiovascular system. This study aimed to evaluate the vascular endothelial function, arterial stiffness, inflammatory status, and circulating microparticle (MP) levels in PExG patients compared with those in primary open-angle glaucoma (POAG) patients and control subjects., Methods: Vascular endothelial function was evaluated by flow-mediated dilation. Pulse wave velocity and augmentation index were measured as indices of aortic stiffness and arterial wave reflections, respectively. Growth-differentiation factor-15 and intercellular adhesion molecule1 levels were measured to evaluate the systemic inflammatory status. Circulating MPs that constitute an emerging marker of vascular endothelial dysfunction and platelet activation were isolated and analyzed by flow cytometry., Results: There was a stepwise impairment from the control to the POAG patients and PExG subjects in the flow-mediated dilation (8.21%±2.94% vs. 7.56%±3.12% vs. 5.79±3.13, P=0.005), pulse wave velocity (8.14±1.79 vs. 9.21±2.27 vs. 9.95±3.28 m/s, P=0.007), augmentation index (24.71%±7.84% vs. 26.78%±7.21% vs. 29.96%±7.58%, P=0.02), and growth-differentiation factor-15 (P=0.001) and intercellular adhesion molecule1 levels (P=0.08). PExG patients expressed greater levels of total circulating MPs (Annexin V+) (P=0.004) and endothelial-derived MPs (CD144+) (P<0.001) compared with POAG and control subjects., Conclusions: PExG patients with an accumulation of pseudoexfoliative microfibrillar material presented with vascular endothelial dysfunction and arterial wall impairment associated with the levels of circulating proinflammatory molecules and circulating apoptotic endothelial MPs. These findings highlight the underlying systemic pathophysiological mechanisms associated with the progress of the pseudoexfoliative syndrome.

Background/aim: Fuchs' endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral, and irreversible disorder of the corneal endothelium. The purpose of this study was to develop a novel, accurate and high-throughput real-time polymerase chain reaction (PCR) method and melting-curve analysis in order to genotype the rs613872 polymorphism in the transcription factor 4 (TCF4) gene and to implement it on a well-ascertained sample of 22 Greek FECD patients and 58 healthy individuals, age- and sex-matched., Patients and Methods: DNA was extracted from blood samples, which were screened with the DNA sequencing method in order to detect the g.31753T>G/p.L450W (rs8035192) and g.31767C>A/p.Q455K (rs8035191) mutations in a COL8A2 genomic region., Results: TCF4 risk G allele frequency increased to 48% in FECD patients compared to 17% in healthy-subjects [OR=4.82 (95% CI=1.98-11.73)]. No p.L450W and p.Q455K COL8A2 gene mutations were detected., Conclusion: We confirmed that rs613872 in the TCF4 gene is strongly and statistically associated with late-onset FECD in a Greek population., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Glaucoma is a chronic and progressive optic neuropathy which leads to deterioration of visual function. It is estimated to be the second leading cause of severe vision loss and blindness worldwide. Failure of anti-glaucoma medication to sufficiently reduce intraocular pressure (IOP) and poor compliance with medication are indications for glaucoma surgery, for example using glaucoma drainage devices. Our aim was to compare the surgical outcomes following the implantation of Ahmed FP7 and Baerveldt 350 drainage devices., Patients and Methods: Five hundred and fifty-two patients with primary or secondary glaucoma were enrolled in the study. All patients had a history of failed trabeculectomy or other intraocular surgery, and IOP ≥18 mm Hg. The implantation of Ahmed (266 patients) or Baerveldt (286 patients) devices was randomly performed in the patients, who were subsequently examined for a period of 5 years. Follow-up visits were scheduled 1 day; 1 week; 1, 3 and 6 months; and 1, 1.5, 2, 3, 4 and 5 years postoperatively., Results: Significant reduction of IOP was achieved in both groups. Ahmed valve (28.3±9.3, 13.4±6.9, 14.2±6 and 12.7±4.5 mmHg at baseline, 1, 3, and 5 years postoperatively, respectively) resulted in significantly greater IOP reduction compared to Baerveldt implant (29.6±10.1, 15.4±5.5, 14.5±5.5 and 14.7±4.4 mmHg at baseline, 1, 3, and 5 years postoperatively, respectively). A significantly lower number of medications was required in the Ahmed group in comparison to the Baerveldt one (Ahmed group: 1.5±1.4, 1.4±1.5 and 1.8±1.5; Baerveldt group: 1.9±1.3, 1.9±1.3 and 2.2±1.4, respectively). The incidence of treatment failure and the rate of glaucoma reoperation were significantly higher in the Baerveldt group (40%) compared to the Ahmed group (17%)., Conclusion: Ahmed drainage implantation seemed to outclass that using the Baerveldt device in our study, in terms of efficacy and success rate., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications., Objective: To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM., Methods: Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry., Results: Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299., Conclusion: Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ocular involvement occurs in sarcoidosis (Sar) patients mainly in the form of uveitis. This study was designed to determine if uveitis in Sar patients is associated with vascular impairment. We enrolled 82 Sar patients and 77, age and sex matched, control subjects (Cl). Sar patients were divided into those with ocular sarcoidosis (OS) and those without ocular sarcoidosis (WOS). Endothelial function was evaluated by flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Although there was no significant difference in sex, age and mean arterial pressure, patients with OS compared to WOS patients and Cl subjects had impaired FMD (p<0.001), increased AIx (p=0.02) and increased PWV (p=0.001). Interestingly, impaired FMD in Sar patients was independently, from possible covariates (age, sex, smoking habits, arterial hypertension, dyslipidemia), associated with increased odds of ocular involvement (odds ratio=1.69, p=0.001). More precisely ROC curve analysis revealed that FMD had a significant diagnostic ability for the detection of OS (AUC=0.77, p<0.001) with a sensitivity of 79% and a specificity of 68% for an FMD value below 6.00%. To conclude in the present study we have shown that ocular involvement in Sar patients is associated with impaired endothelial function and increased arterial stiffness. These results strengthen the vascular theory which considers uveitis a consequence of vascular dysfunction in Sar patients and reveals a possible clinical importance of the use of endothelial function tests., (Copyright © 2015 Elsevier Inc. All rights reserved.)