Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis.

BACKGROUND: The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO. METHODS: We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (P-value < 5 × 10-8) leveraging data from a genome-wide association study (GWAS) (N = 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (P-value < 5 × 10-8) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association. RESULTS: MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26; p-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods. CONCLUSION: Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.

Central corneal thickness and the risk of primary open-angle glaucoma: a Mendelian randomisation mediation analysis.

BACKGROUND: The association of central corneal thickness (CCT) with primary open-angle glaucoma (POAG) remains uncertain. Although several observational studies assessing this relationship have reported an inverse association between CCT and POAG, this could be the result of collider bias. In this study, we leveraged human genetic data to assess through Mendelian randomisation (MR) the effect of CCT on POAG risk and whether this effect is mediated by intraocular pressure (IOP) changes. METHODS: We used 24 single-nucleotide polymorphisms (SNPs) associated with CCT (p value<5×10-8) from a genome-wide association study (GWAS) (N=17 803) provided by the International Glaucoma Genetics Consortium and 53 SNPs associated with IOP (p value<5×10-8) from a GWAS of the UK Biobank (UKBB) (N=97 653). We related these instruments to POAG using a GWAS meta-analysis of 8283 POAG cases and 753 827 controls from UKBB and FinnGen. RESULTS: MR analysis suggested a positive association between CCT and POAG (OR of POAG per 50 µm increase in CCT: 1.38; 95% CI: 1.18 to 1.61; p value<0.01). MR mediation analysis showed that 28.4% of the total effect of CCT on POAG risk was mediated through changes in IOP. The primary results were consistent with estimates of pleiotropy-robust MR methods. CONCLUSION: Contrary to most observational studies, our results showed that a higher CCT is associated with an increased risk of POAG.

Bilateral Late-Onset Pigment Dispersion Syndrome following Implantable Collamer Lens Surgery: A Case Report.

Introduction: We report a case of bilateral pigment dispersion syndrome after 13 years of uncomplicated implantable collamer lens (ICL) surgery. Case Presentation: A 53-year-old woman was referred from her optometrist to our glaucoma clinic due to early superonasal visual field loss in both eyes. She was asymptomatic with no changes in visual acuity and had undergone bilateral ICL implantation 13 years ago to correct her high myopia. Clinical examination revealed pigment deposition on the corneal endothelium, iris transillumination defects, and iris vaulting at the areas of contact with the ICL. Gonioscopy showed open angles with significant pigmentation of the trabecular meshwork. The diagnosis of pigment dispersion syndrome secondary to ICL implantation was made, and subsequent follow-up visits demonstrated normal intraocular pressure IOP and stable visual fields. Conclusion: Pigmentary dispersion syndrome can occur several years after ICL implantation. This case report emphasizes the need for long-term follow-up and monitoring after ICL surgery.

Optical Coherence Tomography Angiography Changes in Patients Diagnosed With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to assess the association between optical coherence tomography angiography (OCTA) parameters and acute coronary syndrome (ACS). Two independent reviewers searched the electronic databases (MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, Embase (Excerpta Medica Database), Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform) from inception until April 2023. According to the inclusion criteria of this review, eligible were observational studies, randomized control trials, and registry/database studies that included the eyes of adult ACS patients and assessed OCTA parameters within the macula. The pooled standardized mean differences (SMD) between patients diagnosed with ACS and healthy controls with a confidence interval (CI) of 95% were calculated using the Hartung-Knapp-Sidik-Jonkman random-effects method. The heterogeneity was assessed by I2 and the Cochran Q and a random effects model was applied. Seven studies were eligible and included in our systematic review (n = 898), of which three were included in the meta-analysis (n = 341). The pooled SMD in the superficial vascular plexus (SVP), deep vascular plexus (DVP), and foveal avascular zone (FAZ) were -0.46 (95% CI: -0.94 to 0.01, p = 0.05, I2 = 0%, three studies), -0.10 (95% CI: -3.20 to 3.00, p = 0.75, I2 = 67%, two studies), and 0.43 (95% CI: -1.22 to 2.09, p = 0.38, I2 = 92%, three studies), respectively. Our findings suggest that there are no differences in OCTA metrics between ACS patients and healthy individuals.

Associations of Dietary Factors with Cutaneous Melanoma: A Case-Control Study in Greece with Literature Review.

INTRODUCTION: It has been postulated that nutrition may influence the risk for cutaneous melanoma (CM); therefore, we aimed to assess the associations of food groups and individual nutrient intakes with CM in a Greek population. METHODS: In this case-control study, 151 patients with histologically confirmed CM, newly diagnosed and treated in the Oncology Department of the "Laikon" University Hospital (Athens, Greece), and 151 age- and sex-matched healthy individuals residing in the Athens metropolitan area, recruited among participants for routine health examinations, were included. All participants completed a questionnaire comprising anthropometric measurements, sociodemographic, lifestyle, and health-related variables. A validated, semiquantitative food frequency questionnaire was used to assess average consumption of 136 food items during the 12 months preceding the onset of disease. Multivariate conditional regression models were used to derive odds ratios (ORs) with 95% confidence intervals (95% CI) regarding the association of nine food groups and seven macronutrients with CM. RESULTS: Statistically significant positive associations with CM were found with higher energy intake (OR: 1.67, 95% CI: 1.22-2.30) and intake of saturated fatty acids (OR: 2.28, 95% CI: 1.00-5.28), after adjusting for sun sensitivity, major depression history, and alcohol intake. Inverse associations with higher intake of milk and dairy products (OR: 0.65, 95% CI: 0.48-0.88), fruits (OR: 0.68, 95% CI: 0.51-0.90), added lipids (OR: 0.65, 95% CI: 0.47-0.91), and sugars and syrups (OR: 0.70, 95% CI: 0.53-0.93) were also observed. CONCLUSIONS: Beyond intrinsic risk factors, our results support associations of CM with multiple food groups and nutrients; if confirmed by prospective studies, these findings can add further knowledge about this fatal cancer.

UGH Syndrome Resolution after IOL Explantation and Concomitant Carlevale IOL Implantation.

OBJECTIVE: To examine the use of Carlevale IOL placement in patients with UGH, and to evaluate surgical outcomes. DESIGN: In this retrospective study, 28 patients with UGH syndrome that were subjected to IOL explantation and concomitant Carlevale IOL implantation were included in the study. METHODS: Information about VA, IOP, number of glaucoma medication, need for glaucoma surgery, presence of hemorrhage and inflammation were recorded up to 6 months after the procedure. RESULTS: We found a statistically significant increase in mean visual acuity and complete resolution of uveitis in all patients. Mean IOP and the mean number of glaucoma medications were significantly decreased postoperatively, while 14% of patients required additional glaucoma surgery. CONCLUSIONS: IOL explantation and concomitant Carlevale IOL implantation may provide a viable solution for UGH syndrome resolution, increases visual acuity, and decreases the need for glaucoma medication.

Cannabis use and the risk of primary open-angle glaucoma: a Mendelian randomization study.

Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma (POAG) remains unclear. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) whether cannabis use affects POAG. We used five single-nucleotide polymorphisms (SNPs) associated with lifetime cannabis use (P-value < 5 × 10-8) from a genome-wide association study (GWAS) (N = 184,765) by the International Cannabis Consortium, 23andMe, and UK Biobank and eleven SNPs associated with cannabis use disorder (P-value < 5 × 10-7) from a GWAS meta-analysis of (17,068 cases and 357,219 controls of European descent) from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative Psychiatric Research, and deCode. We associated the selected five SNPs from the GWAS of lifetime cannabis use and the eleven SNPs from the GWAS of cannabis use disorder, with the largest to date GWAS meta-analysis of POAG (16,677 cases and 199,580 controls). MR analysis suggested no evidence for a causal association of lifetime cannabis use and cannabis use disorder with POAG (odds ratio (OR) of outcome per doubling of the odds of exposure (95% confidence interval): 1.04 (0.88; 1.23) for lifetime cannabis use and 0.97 (0.92; 1.03) for cannabis use disorder). Sensitivity analyses to address pleiotropy and weak instrument bias yielded similar estimates to the primary analysis. In conclusion, our results do not support a causal association between cannabis use and POAG.

Correlation Between Coronary and Retinal Microangiopathy in Patients With STEMI.

Purpose: To investigate the morphological and functional correlation between microvascular retinal changes in optical coherence tomography angiography (OCTA) and the microvascular coronary circulation in patients with ST elevation myocardial infarction (STEMI) coronary heart disease (CHD). Methods: A total of 330 eyes from 165 participants (88 cases and 77 controls) were enrolled and imaged. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vascular density was measured in the central (1 mm) and perifoveal (1-3 mm) areas and in the superficial foveal avascular zone (FAZ) and choriocapillaris (3 mm). These parameters were then correlated to the left ventricular ejection fraction (LVEF), and the number of affected coronary arteries. Results: Decreased vessel densities in the SCP and DCP and choriocapillaris were positively correlated to the LVEF values (P = 0.006, P = 0.026, and P = 0.002, respectively). No statistically significant correlation between the SCP and DCP central area or FAZ area was found. Regarding the number of affected vessels, significant negative correlations were revealed for the SCP and DCP central vessel densities (P < 0.001 and P < 0.001, respectively) and the SCP perifoveal vascular density (P = 0.009). Conclusions: OCTA vascular indices are significantly correlated with morphological and functional parameters in patients with STEMI CHD. SCP vascular density especially seems to be a promising biomarker for the extent of both macrovascular damage (number of affected coronary arteries) and microvascular damage, as mirrored in the decreased LVEF at admission. Translational Relevance: OCTA vascular indices offer a valuable insight into the microvascular status of coronary circulation.

A closed-loop audit of the prescription practice of topical antibiotics for acute infective conjunctivitis.

Objective: The implementation of guideline recommendations for antibiotics prescription for the management of patients with acute infective conjunctivitis (AIC) in primary care departments remains below par. Our objective was to assess the impact of clinical audit on adherence to evidence-based indications for prescription of antibiotic eye drops in patients diagnosed with AIC, in the setting of a primary care practice in western Greece. Methods: We conducted a retrospective audit to evaluate the current prescription practice of antibiotics for the management of AIC. Following evidence-based indications for the prescription of antibiotics in AIC through literature search, and in combination with discussion and collaboration with the primary care doctors of our department, we formulated and implemented guidelines for the management of AIC. We then performed a prospective re-audit to assess the management of patients with AIC after local implementation of the guidelines. Results: A total of 158 cases were audited in the first cycle before the introduction of the guidelines, from 15th June 2019 to 7th March 2020, and 26 cases after, from 10th March 2020 to 20th November 2020. The compliance with the guidelines regarding antibiotics prescription was significantly improved from 12.0% to 84.6% between the first and the second cycles of audit. Conclusions: In this study, with the local introduction of guidelines, clinical audit significantly improved the prescription practice of topical antibiotics in patients with AIC in a primary care department. Abbreviations: AIC = acute infective conjunctivitis.

The Multifarious Effects of Various Glaucoma Pharmacotherapy on Corneal Endothelium: A Narrative Review.

Corneal endothelium is a single cell layer that is mainly responsible for maintaining corneal clarity. Endothelial damage secondary to toxicity, stress, or genetic predisposition are common and in conjunction with the low regenerative ability of the cells, making their preservation critical for maintaining visual acuity. Patients with glaucoma, who are estimated to be close to 80 million worldwide, have a plethora of reasons for developing endothelial damage, being exposed to a spectrum that extends from various medical and surgical interventions to the disease itself. The wide spectrum of glaucoma pharmacotherapy that has been recently extended by addition of newer classes of medications has been the focus of extensive research on its effects on corneal endothelium. Both basic and clinical research have attempted to shine a light on the complex mechanisms associated with the effects of glaucoma medication on corneal endothelium and to answer the important question as to whether these findings are clinically significant. The aim of this review is to summarize and present current literature of the various findings, both from in vivo and in vitro studies that have focused on the complex relationship between different classes of glaucoma medication and their effect on corneal endothelium.

Optical coherence tomography angiography in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: To examine the association between optical coherence tomography angiography (OCTA) retinal measurements and Parkinson's disease (PD). METHODS: We searched MEDLINE and EMBASE from inception up to November 5th, 2021 for studies examining the differences between OCTA retinal measurements in PD patients and healthy controls. We used the Hartung-Knapp-Sidik-Jonkman random-effects method to combine study-specific standardized mean differences (SMD) in pooled effect estimates and a meta-analytic extension of the E-value metric to quantify the confounding bias capable of nullifying the pooled estimates. RESULTS: Nine eligible studies for our systematic review were identified through our search strategy. The pooled SMD between the retinal vessel density of PD patients and healthy participants in the whole superficial vascular plexus (SVP), foveal SVP, parafoveal SVP and foveal avascular zone (FAZ) was -0.68 (95% CI: -1.18 to -0.17, p value = 0.02, n = 7 studies), -0.14 (95% CI: -0.88 to 0.59, p value = 0.62, n = 5 studies), -0.59 (95% CI: -1.41 to 0.23, p value = 0.12, n = 5 studies) and -0.20 (95% CI: -0.79 to 0.38, p value = 0.39, n = 5 studies), respectively. An unmeasured confounder would need to be associated with a 3.01-fold, 1.54-fold, 2.81-fold and 1.70-fold increase in the risk of PD and OCTA retinal measurements, in order for the pooled SMD estimate of vessel density in whole SVP, parafoveal SVP and FAZ, respectively, to be nullified. CONCLUSIONS: Our results provide evidence on an inverse association between whole SVP vessel density and PD.

The Effect of the Water Drinking Test on Ocular Parameters and Choroidal Thickness in Glaucoma Suspects.

Background and objectives: We aimed to evaluate the effects of the water drinking test (WDT) on several systemic and ocular parameters, including choroidal thickness, which was assessed through optical coherence tomography angiography (OCTA), in glaucoma suspects. Materials and Methods: A total of 40 eyes from 20 glaucoma suspects without any systemic or ocular diseases were included in this prospective observational study. All the participants undertook the WDT, which required the drinking of 1 L of table water in 5 min. The outcome measures included IOP, systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), mean ocular perfusion pressure (MOPP), ocular pulse amplitude (OPA), and subfoveal and peripapillary choroidal thickness, which were assessed at baseline and at four 15 min intervals after the WDT. Generalized least squares models and mixed model analyses that take into account repeated measurements were used to assess the changes over time of these parameters. Results: All the ocular and systemic parameters showed statistically significant changes at all time points compared to baseline apart from choroidal thickness. The peak changes were an IOP of 20.1 mmHg versus 17.3 mmHg at 45 min, an SBP of 137.6 mmHg versus 125 mmHg at 30 min, a DBP of 95.9 mmHg versus 85.7 mmHg at 15 min, and an MOP of 53.51 mmHg versus 48.89 mmHg at 15 min. Conclusions: Despite elevations in IOP and significant changes in all the assessed systemic parameters, the WDT was not associated with changes in choroidal thickness in glaucoma suspects.

Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial.

OBJECTIVE: Randomized controlled trials comparing tocilizumab and baricitinib in patients with coronavirus disease 2019 (COVID-19) are needed. This was an open-label, randomized controlled trial aiming to address this unmet need. METHODS: To determine whether baricitinib was non-inferior to tocilizumab, we assessed whether the upper boundary of the two-sided 95% CI of the hazard ratio (HR) did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10. RESULTS: We assigned 251 patients with COVID-19 and a PaO2/FiO2 ratio of <200 to receive either tocilizumab (n = 126) or baricitinib (n = 125) plus standard of care. Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (mechanical ventilation or death for patients who received baricitinib, 39.2% [n = 49/125]; mechanical ventilation or death for patients who received tocilizumab, 44.4% [n = 56/126]; HR, 0.83; 95% CI, 0.56-1.21; p 0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (patients who received baricitinib- discharged alive: 58.4% [n = 73/125] vs. patients who received tocilizumab- discharged alive: 52.4% [n = 66/126]; HR, 0.85; 95% CI, 0.61-1.18; p < 0.001 for non-inferiority). There was no significant difference between the baricitinib and tocilizumab arms in the change in WHO scale at day 10 (0.0 [95% CI, 0.0-0.0] vs. 0.0 [95% CI, 0.0-1.0]; p 0.83). DISCUSSION: In the setting of this trial, baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19.

Two Year Randomized Prospective Comparison of Ahmed Valve Versus Baerveldt Implant in Vitrectomized Eyes.

PRCIS: Ahmed Valve and Baerveldt shunt are efficacious options in vitrectomized eyes. Baerveldt implant achieves a lower mean intraocular pressure (IOP) at 2 years, with fewer medications and a higher percentage of medication-free patients. PURPOSE: To investigate and compare the efficacy and complications between Ahmed FP7 Glaucoma Valve (AGV) and Baerveldt 101-350 Glaucoma Implant (BGI) in vitrectomized eyes. MATERIALS AND METHODS: In this single-center randomized clinical trial, 43 vitrectomized eyes (39 patients) underwent glaucoma drainage device implantation. Eyes were randomized to receive either an AGV (FP7) or a BGI (101-350) and were followed for 2 years. Surgical success was defined as an IOP measurement≤18 mm Hg and≥5 mm Hg with or without glaucoma medication at 2 or more sequential visits after 3 months. The primary outcome was the comparison of the success rate at 2 years, while mean IOP, mean number of medications, and number of complications were considered secondary outcomes. RESULTS: Kaplan-Meier estimates of the 2-year success rates in IOP control after GDD implantation were similar between the 2 groups; AGV group 81.8% (95% CI: 67.2%-99.6%) and BGI group 85.7% (95% CI: 72.0%-100.0%), (log-rank test P value = 0.74). Patients in the BGI group had a statistically significant lower mean IOP compared with the AGV group in all follow-up visits at 2, 6, 12, and 24 months (11.62 vs. 17.45 mm Hg at the latter P value <0.001). The BGI group required a significantly lower number of medications for IOP control at the 2-year visit compared with the AGV group (0.76±0.99 vs. 1.5±1.06 P value = 0.02) but had a higher number of complications (62% vs. 41%, respectively). CONCLUSIONS: GDDs provide a viable solution for IOP control in vitrectomized eyes. Based on our prospective comparison, both Ahmed FP7 Glaucoma Valve and Baerveldt 101-350 Glaucoma Implant are efficacious options.

Nutritional Status at Diagnosis as Predictor of Survival from Childhood Cancer: A Review of the Literature.

Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30-50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.

Maternal lifestyle factors and risk of neuroblastoma in the offspring: A meta-analysis including Greek NARECHEM-ST primary data.

The etiology of childhood neuroblastoma remains largely unknown. In this systematic review and meta-analysis, we summarized and quantitatively synthesized published evidence on the association of maternal modifiable lifestyle factors with neuroblastoma risk in the offspring. We searched MEDLINE up to December 31, 2020 for eligible studies assessing the association of maternal smoking, alcohol consumption and nutritional supplementation during pregnancy with childhood (0-14 years) neuroblastoma risk. Random-effects models were run, and summary odds ratios (OR) and 95% confidence intervals (95% CI) on the relevant associations were calculated, including estimates derived from primary data (n = 103 cases and n = 103 controls) of the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) case control study (2009-2017) in Greece. Twenty-one eligible studies amounting 5163 cases participating in both case-control and cohort/linkage studies were included in the meta-analysis. Maternal smoking and alcohol consumption were not statistically significantly associated with neuroblastoma risk (summary ORsmoking: 1.08, 95% CI: 0.96-1.22, I2 =12.0%, n = 17 studies; summary ORalcohol: 1.01, 95% CI: 0.82-1.18, I2 =0.0%, n = 8 studies). By contrast, maternal vitamin intake during pregnancy was associated with significantly lower neuroblastoma risk (summary OR: 0.57, 95% CI: 0.34-0.95, I2 =58.9%, n = 4 studies). The results of the largest to-date meta-analysis point to an inverse association between vitamin intake during pregnancy and childhood neuroblastoma risk. Future longitudinal studies are needed to confirm and further specify these associations as to guide preventive efforts on modifiable maternal risk factors of childhood neuroblastoma.

Optical coherence tomography angiography in Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: To assess the association between optical coherence tomography angiography (OCTA) retinal measurements and Alzheimer's disease (AD). METHODS: We searched MEDLINE and EMBASE from inception up to October 28th, 2020 for studies assessing the association between OCTA retinal measurements and AD. Estimates from eligible studies were meta-analysed and pooled standardized mean differences (SMDs) between AD patients and healthy participants with corresponding 95% confidence intervals (95% CI) were calculated, using the Hartung-Knapp/Sidik-Jonkman random-effects method. In addition, we quantified the minimum strength on the risk ratio scale (E value) required for an unmeasured confounder to nullify these associations. RESULTS: Ten eligible studies for our systematic review were identified through our search strategy. The pooled SMD between the retinal vessel density of AD patients and healthy participants in the whole superficial vascular plexus (SVP), parafoveal SVP and foveal avascular zone (FAZ) was -0.41 (95% CI: -0.69 to -0.13, p value = 0.01, I2 = 15%, seven studies), -0.51 (95% CI: -0.84 to -0.18, p value = 0.01, I2 = 40%, six studies), and 0.87 (95% CI: -0.03 to 1.76, p value = 0.05, I2 = 91%, seven studies), respectively. An unmeasured confounder would need to be associated with a 2.26-, 2.56- and 3.82-fold increase in the risk of AD and OCTA retinal measurements, in order for the pooled SMD estimate of vessel density in whole SVP, parafoveal SVP and FAZ, respectively, to be nullified. CONCLUSIONS: In our study, whole and parafoveal SVP vessel density were inversely associated with AD. However, prospective longitudinal studies with larger sample sizes are needed to furtherly assess these associations.

Prediction of type 2 diabetes mellitus based on nutrition data.

Numerous predictive models for the risk of type 2 diabetes mellitus (T2DM) exist, but a minority of them has implemented nutrition data so far, even though the significant effect of nutrition on the pathogenesis, prevention and management of T2DM has been established. Thus, in the present study, we aimed to build a predictive model for the risk of T2DM that incorporates nutrition data and calculates its predictive performance. We analysed cross-sectional data from 1591 individuals from the population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013-14) and used a bootstrap enhanced elastic net penalised multivariate regression method in order to build our predictive model and select among 193 food intake variables. After selecting the significant predictor variables, we built a logistic regression model with these variables as predictors and T2DM status as the outcome. The values of area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of our predictive model were calculated. Eleven out of the 193 food intake variables were selected for inclusion in our model, which yielded a value of area under the ROC curve of 0⋅79 and a maximum PPV, NPV and accuracy of 0⋅37, 0⋅98 and 0⋅91, respectively. The present results suggest that nutrition data should be implemented in predictive models to predict the risk of T2DM, since they improve their performance and they are easy to assess.

Association between cardiorespiratory fitness and handgrip strength with age-related macular degeneration: a population-based study.

AIM: To assess whether cardiorespiratory fitness (CRF) and handgrip strength, two objective markers of physical fitness, are associated with age-related macular degeneration (AMD). METHODS: We analysed cross-sectional data from the population-based Study of Health in Pomerania (2008-2012) including 1173 adult men and women aged 20-79 years. Fundus photography of the central retina was recorded with a non-mydriatic camera, and images were graded according to an established clinical AMD classification scale by an experienced reader. CRF was measured using peak oxygen uptake (peakVO2), oxygen uptake at the anaerobic threshold (VO2@AT), and maximum power output (Wmax) from standardised cardiopulmonary exercise testing on a bicycle ergometer according to a modified Jones protocol. Handgrip strength was assessed using a handheld dynamometer. Adjusted prevalence ratios (PR) for the associations of peakVO2, VO2@AT, Wmax and handgrip strength with AMD were derived from multivariable Poisson regression models. RESULTS: PeakVO2, VO2@AT, Wmax and handgrip strength were not associated with AMD. Adjusted PR for AMD associated with a 1-SD increment in peakVO2, VO2@AT, Wmax and handgrip strength were 1.05 (95% CI 0.82 to 1.34), 0.96 (95% CI 0.78 to 1.18), 1.10 (95% CI 0.86 to 1.41) and 1.01 (95% CI 0.79 to 1.30), respectively. These associations were not modified by age, sex, smoking, body mass index and diabetes. Estimates in sensitivity analysis for confounding, selection bias and missing data were similar. CONCLUSION: In our study, CRF and handgrip strength were not associated with AMD. Nevertheless, longitudinal studies with bigger sample sizes are needed to furtherly examine these associations.

Maternal lifestyle characteristics and Wilms tumor risk in the offspring: A systematic review and meta-analysis.

BACKGROUND: Little is known about the etiology of childhood Wilms tumor (WT) and potentially modifiable maternal risk factors, in particular. METHODS: Unpublished data derived from the hospital-based, case-control study of the Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) were included in an ad hoc conducted systematic literature review and meta-analyses examining the association between modifiable maternal lifestyle risk factors and WT. Eligible data were meta-analysed in separate strands regarding the associations of WT with (a) maternal folic acid and/or vitamins supplementation, (b) alcohol consumption and (c) smoking during pregnancy. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale. RESULTS: Effect estimates from 72 cases and 72 age- and sex-matched controls contributed by NARECHEM-ST were meta-analysed together with those of another 17, mainly medium size, studies of ecological, case-control and cohort design. Maternal intake of folic acid and/or other vitamins supplements during pregnancy was inversely associated with WT risk (6 studies, OR: 0.78; 95 %CI: 0.69-0.89, I2 = 5.4 %); of similar size was the association for folic acid intake alone (4 studies, OR: 0.79; 95 %CI: 0.69-0.91, I2 = 0.0 %), derived mainly from ecological studies. In the Greek study a positive association (OR: 5.31; 95 %CI: 2.00-14.10) was found for mothers who consumed alcohol only before pregnancy vs. never drinkers whereas in the meta-analysis of the four homogeneous studies examining the effect of alcohol consumption during pregnancy the respective overall result showed an OR: 1.60 (4 studies, 95 %CI: 1.28-2.01, I2 = 0.0 %). Lastly, no association was seen with maternal smoking during pregnancy (14 studies, OR: 0.93; 95 %CI: 0.80-1.09, I2 = 0.0 %). CONCLUSIONS: In the largest to-date meta-analysis, there was an inverse association of maternal folic acid or vitamins supplementation with WT risk in the offspring, derived mainly from ecological studies. The association with maternal alcohol consumption found in our study needs to be further explored whereas no association with maternal smoking was detected. Given the proven benefits for other health conditions, recommendations regarding folic acid supplementation as well as smoking and alcohol cessation should apply. The maternal alcohol consumption associations, however, should be further explored given the inherent limitations in the assessment of exposures of the published studies.