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Purpose: To determine the characteristics of diabetic macular edema (DME) patients refractory to intravitreal bevacizumab (IVB) treatments and an additional dexamethasone implant. Methods: We classified 119 DME patients according to whether or not they are responsive to 3 consecutive monthly anti-VEGF treatments and/or an additional dexamethasone implant. We compared their concentrations of IL (interleukin)-1β, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor as well as their optical coherence tomography (OCT) findings, and baseline characteristics. We used logistic regression analyses to identify preoperative factors related to refractoriness to treatments. Results: Of 119 treatment-naïve DME patients, 50 (42.02%) patients showed responsiveness [central subfield thickness (CST) < 300μm] after 3 IVBs, and 59 (49.58%) patients showed responsiveness after an additional dexamethasone implant, but 10 (8.40%) patients showed CST 300 ≥ μm even after both treatments. Refractory DME patients showed significantly higher number of hyperreflective foci (HF) in the OCT and higher average level of aqueous IL-1β at baseline (p<0.001 and p = 0.042, respectively). In the logistic regression analysis, higher number of HF in the OCT was associated with the refractoriness to both treatments (odds ratio [OR]: 7.03, p = 0.007) Conclusions: Higher number of HF in the OCT at the initial visit was associated with poor responses to IVBs and an additional dexamethasone implant. [ABSTRACT FROM AUTHOR]

Objective: Detection of vascular endothelial growth factor (VEGF) levels in ocular tissue may perhaps provide insight into the role of VEGF in the pathogenesis and progression of diabetic retinopathy (DR). The aim of this study was to evaluate the levels of VEGF in tears and serum amongst type 2 diabetes mellitus (DM) patients. Methods: A comparative cross-sectional study was conducted between August 2016 and May 2018 involving type 2 DM patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Tear samples were collected using no.41 Whatman filter paper (Schirmer strips) and 5 mL blood samples were drawn by venous puncture. VEGF levels in tears and serum were measured by enzyme-linked immunosorbent assay. Results: A total of 88 type 2 DM patients (no DR: 30 patients, NPDR: 28 patients, PDR: 30 patients) were included in the study. Mean tear VEGF levels were significantly higher in the NPDR and PDR groups (114.4 SD 52.5 pg/mL and 150.8 SD 49.7 pg/mL, respectively) compared to the no DR group (40.4 SD 26.5 pg/mL, p < 0.001). There was no significant difference in the mean serum VEGF levels between the three groups. There was a fair correlation between serum and tear VEGF levels (p = 0.015, r = 0.263). Conclusion: VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR. There was a fair correlation between serum and tear VEGF levels. Detection of VEGF in tears is a good non-invasive predictor test for the severity of DR. A large cohort study is needed for further evaluation. [ABSTRACT FROM AUTHOR]

In the United States, there is no reliable data to describe the prevalence of eye diseases leading to visual impairment and little active surveillance to address this knowledge gap. Data that is readily available from many state blind registries may provide helpful information on trends and causes of blindness. We analyzed new registrations with the Oregon Commission for the Blind (OCB) and Oregon State Department of Administrative Services (DAS) from 1961 to 2016 for causes of and trends in blindness. Persons with blindness self-refer into the OCB registry and the Oregon State Department of Administrative Services (DAS) includes those receiving social security disability financial support and other state services. Data for 9,273 blind persons registered were analyzed. The most frequent causes of blindness were age related macular degeneration (AMD) 3,308 (38%), followed by diabetic retinopathy (DR) 729 (8%), congenital conditions 697 (8%), optic nerve atrophy 611 (7%), glaucoma 549 (6%), retinitis pigmentosa 546 (6%), retinopathy of prematurity192 (2%), cataract 180 (2%), and trauma 174 (2%). The mean age of onset of blindness was younger for Blacks (31 years) and Hispanics (33 years) than for Whites (44 years). Analysis of state-based registries can provide useful and locally relevant vision and eye health data where little information is otherwise available. [ABSTRACT FROM AUTHOR]

Since both retinopathy and nephropathy are major diabetic microvascular complications, we investigated whether severity of diabetic retinopathy (DR) has adverse effects on renal function and albuminuria in the patients with type 2 diabetes mellitus (DM). We screened 2,197 adult patients with type 2 DM who had undergone fundus exam between August 2006 and February 2014. Among them, 1,592 subjects with available serial renal function and albuminuria measurement were included in the analysis. DR status was classified as no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). The risk of CKD progression was assessed according to DR severity. A total of 384 (24.1%) had NPDR and 202 (12.7%) had PDR at either eye. The mean follow-up period was 5.6±2.1 years. DR was associated with lower body mass index, lower plasma hemoglobin, lower serum albumin level, longer duration of DM, poorer control of blood sugar, lower estimated glomerular filtration rate (eGFR), and greater amount of albuminuria. Interestingly, baseline DR severity was associated with faster renal function decline and greater albuminuria progression. In multivariate analysis, NPDR had 2.9 times and PDR had 16.6 times higher risk for CKD progression. Our findings showed that baseline DR severity is a prognostic factor for future CKD progression in type 2 DM patients. Therefore, clinicians must evaluate DR severity at the first visit and closely monitor renal function and albuminuria in the subjects with severe DR. [ABSTRACT FROM AUTHOR]

Retinal fundus imaging is a non-invasive method that allows visualizing the structure of the blood vessels in the retina whose features may indicate the presence of diseases such as diabetic retinopathy (DR) and glaucoma. Here we present a novel method to analyze and quantify changes in the retinal blood vessel structure in patients diagnosed with glaucoma or with DR. First, we use an automatic unsupervised segmentation algorithm to extract a tree-like graph from the retina blood vessel structure. The nodes of the graph represent branching (bifurcation) points and endpoints, while the links represent vessel segments that connect the nodes. Then, we quantify structural differences between the graphs extracted from the groups of healthy and non-healthy patients. We also use fractal analysis to characterize the extracted graphs. Applying these techniques to three retina fundus image databases we find significant differences between the healthy and non-healthy groups (p-values lower than 0.005 or 0.001 depending on the method and on the database). The results are sensitive to the segmentation method (manual or automatic) and to the resolution of the images. [ABSTRACT FROM AUTHOR]

Purpose: To classify the risk factors that contribute to the development versus progression of retinopathy of prematurity (ROP). Methods: The medical records of premature infants born with a birth weight (BW) less than 1501 g or a gestational age (GA) of 32 weeks or less were retrospectively reviewed. Twenty potential risk factors that may influence the development or progression of ROP were analyzed by univariate and multivariate logistic regression analyses. The progression of ROP was defined as type 1 ROP, threshold ROP, or aggressive posterior ROP for which treatment was recommended. Results: A total of 324 eyes were included; 157 eyes (48.5%) showed ROP development, and 48 eyes exhibited ROP progression (14.8% of all eyes and 30.6% of the ROP-developed eyes). According to the univariate and multivariate logistic regression analyses, prenatal steroid use, GA, the duration of mechanical ventilation, and respiratory distress syndrome were associated with the development of ROP. However, GA, bronchopulmonary dysplasia, the number of red blood cell units transfused, intraventricular hemorrhage, and periventricular leukomalacia were significantly correlated with ROP progression. Conclusion: The risk factors that influenced ROP development versus ROP progression were not identical. Evaluating these risk factors during screening of high-risk premature infants will help determine the appropriate timing of examinations and treatment. [ABSTRACT FROM AUTHOR]

Purpose: To explore the relationships between vessel density (VD) in the retinal vascular plexuses with the thickness and structural changes of their corresponding retinal layers in patients with diabetic retinopathy (DR). Methods: Retrospective analysis of 17 eyes of 17 Type 1 diabetes (T1D) patients with severe non-proliferative or proliferative DR and no current or past macular edema. Seventeen age- and sex-matched healthy subjects were included as controls. Using optical coherence tomography (OCT) and OCT-angiography (OCTA), VD was measured in the superficial vascular plexus (SVP) and deep vascular complex (DVC) that includes the intermediate (ICP) and deep capillary plexuses (DCP), and compared to the retinal thickness (RT) of the inner (from the inner limiting membrane to the inner plexiform layer) and intermediate (inner nuclear and outer plexiform layer) retinal layers. The correlation between the inner and intermediate RT and the VD of the corresponding vascular networks (SVP and DVC, respectively) was assessed. All OCT and OCTA examinations were performed using the RTVue XR Avanti (Optovue, Fremont, CA). Results: The inner RT and VD in all plexuses were significantly reduced in T1D patients compared to healthy subjects. The capillary drop-out patterns were polygonal and well-defined in the SVP while the ICP and DCP showed a more diffuse capillary rarefaction and a VD that varied in the same proportion. The inner RT significantly correlated with VD in the SVP (r = 0.71 in healthy subjects and r = 0.62 in T1D patients, p <0.01). The intermediate RT did not significantly correlate with VD in the DVC. Conclusions: In T1D subjects, OCTA allowed observing different capillary drop-out patterns in the SVP and in the ICP-DCP, with different structural changes in the corresponding retinal layers, suggesting that they should be considered as distinct anatomical and functional entities. [ABSTRACT FROM AUTHOR]

Purpose: Vitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C. Methods: This prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA). Results: PDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015). Conclusions: Vitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients. [ABSTRACT FROM AUTHOR]

Background: Ischemic retinopathies (IRs) are leading causes of visual impairment. They are characterized by an initial phase of microvascular degeneration and a second phase of aberrant pre-retinal neovascularization (NV). microRNAs (miRNAs) regulate gene expression, and a number play a role in normal and pathological NV. But, post-transcriptional modulation of miRNAs in the eye during the development of IRs has not been systematically evaluated. Aims & methods: Using Next Generation Sequencing (NGS) we profiled miRNA expression in the retina and choroid during vasodegenerative and NV phases of oxygen-induced retinopathy (OIR). Results: Approximately 20% of total miRNAs exhibited altered expression (up- or down-regulation); 6% of miRNA were found highly expressed in retina and choroid of rats subjected to OIR. During OIR-induced vessel degeneration phase, miR-199a-3p, -199a-5p, -1b, -126a-3p displayed a robust decreased expression (> 85%) in the retina. While in the choroid, miR-152-3p, -142-3p, -148a-3p, -532-3p were upregulated (>200%) and miR-96-5p, -124-3p, -9a-3p, -190b-5p, -181a-1-3p, -9a-5p, -183-5p were downregulated (>70%) compared to controls. During peak pathological NV, miR-30a-5p, -30e-5p and 190b-5p were markedly reduced (>70%), and miR-30e-3p, miR-335, -30b-5p strongly augmented (by up to 300%) in the retina. Whereas in choroid, miR-let-7f-5p, miR-126a-5p and miR-101a-3p were downregulated by (>81%), and miR-125a-5p, let-7e-5p and let-7g-5p were upregulated by (>570%) during NV. Changes in miRNA observed using NGS were validated using qRT-PCR for the 24 most modulated miRNAs. In silico approach to predict miRNA target genes (using algorithms of miRSystem database) identified potential new target genes with pro-inflammatory, apoptotic and angiogenic properties. Conclusion: The present study is the first comprehensive description of retinal/choroidal miRNAs profiling in OIR (using NGS technology). Our results provide a valuable framework for the characterization and possible therapeutic potential of specific miRNAs involved in ocular IR-triggered inflammation, angiogenesis and degeneration. [ABSTRACT FROM AUTHOR]

We have attempted to reproduce the results in Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs, published in JAMA 2016; 316(22), using publicly available data sets. We re-implemented the main method in the original study since the source code is not available. The original study used non-public fundus images from EyePACS and three hospitals in India for training. We used a different EyePACS data set from Kaggle. The original study used the benchmark data set Messidor-2 to evaluate the algorithm's performance. We used another distribution of the Messidor-2 data set, since the original data set is no longer available. In the original study, ophthalmologists re-graded all images for diabetic retinopathy, macular edema, and image gradability. We have one diabetic retinopathy grade per image for our data sets, and we assessed image gradability ourselves. We were not able to reproduce the original study's results with publicly available data. Our algorithm's area under the receiver operating characteristic curve (AUC) of 0.951 (95% CI, 0.947-0.956) on the Kaggle EyePACS test set and 0.853 (95% CI, 0.835-0.871) on Messidor-2 did not come close to the reported AUC of 0.99 on both test sets in the original study. This may be caused by the use of a single grade per image, or different data. This study shows the challenges of reproducing deep learning method results, and the need for more replication and reproduction studies to validate deep learning methods, especially for medical image analysis. Our source code and instructions are available at: . [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a complication of diabetes that produces changes in the blood vessel structure in the retina, which can cause severe vision problems and even blindness. In this paper, we demonstrate that by identifying topological features in very high resolution retinal images, we can construct a classifier that discriminates between healthy patients and those with diabetic retinopathy using summary statistics of these features. Topological data analysis identifies the features as connected components and holes in the images and describes the extent to which they persist across the image. These features are encoded in persistence diagrams, summaries of which can be used to discrimate between diabetic and healthy patients. The method has the potential to be an effective automated screening tool, with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the correlations between serum undercarboxylated osteocalcin (ucOC) or osteocalcin (OC) concentrations and %body fat, serum adiponectin and free-testosterone concentration, muscle strength and dose of exogenous insulin in patients with type 1 diabetes. We recruited 73 Japanese young adult patients with childhood-onset type 1 diabetes. All participants were receiving insulin replacement therapy. The correlations between logarithmic serum ucOC or OC concentrations and each parameter were examined. Serum ucOC and OC concentrations were inversely correlated with %body fat (r = -0.319, P = 0.007; r = -0.321, P = 0.006, respectively). Furthermore, multiple linear regression analyses were performed to determine whether or not serum ucOC or OC concentrations were factors associated with %body fat. Serum ucOC and OC concentrations remained significant factors even after adjusting for gender, HbA1c, body weight-adjusted total daily dose of insulin and duration of diabetes (β = -0.260, P = 0.027; β = -0.254, P = 0.031, respectively). However, serum ucOC and OC concentrations were not correlated with serum adiponectin or free-testosterone concentrations, muscle strength or dose of exogenous insulin. In conclusion, our study demonstrates the inverse correlation between serum ucOC or OC concentrations and body fat in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate long-term behavioural and neurodevelopmental complications of neonatal necrotizing enterocolitis at school age. Method: This was a historic cohort study comparing all surviving children born in Denmark between 1st of January 2002 and 31st of December 2011 with a diagnosis of necrotizing enterocolitis to a group of children without necrotizing enterocolitis, but same gestational age, birth weight and year of birth. Outcomes were investigated through a parental questionnaire. The primary outcome was the Strength and Difficulties Questionnaire score and secondary outcomes were cerebral palsy and impaired head growth. Results: Response rates were 50% (163 of 328) and 36% (237 of 652) among children with and without necrotizing enterocolitis, respectively. There was a higher rate of abnormal Strength and Difficulties score (23.9 versus 17.8%), moderate/severe cerebral palsy (3.1 versus 0.9%) and small head circumference for age (11.7 versus 7.2%) among children with necrotizing enterocolitis. However, these differences were all statistically insignificant and did not change significantly by adjustment for potential confounders. Conclusion: To our knowledge, this study includes the largest cohort of necrotizing enterocolitis children evaluated for possible long-term complications at school age. The increased risks of behavioural- and neurodevelopmental impairments were statistically insignificant, moderate in magnitude and may be of little clinical importance for management in the neonatal period or when planning follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To compare swept source OCTA device, with and without the extended field imaging (EFI) technique, to standard fluorescein angiography (FA) in the clinical practice. Methods: Consecutive patients with vascular disorder patients underwent FA with 55-degree lens (Spectralis Heidelberg Engineering, Heidelberg, Germany) and OCTA with the prototype PlexElite (Carl Zeiss Meditec, Dublin, CA) using a 12 mm x 12 mm volume scan pattern centered on the fovea and a prototype of + 20.00-diopter designed specifically by Zeiss. The imaging methods were compared for visible field of view, extension of non-perfused areas, presence and number of neovessels, vessel density (VD) and fractal dimension (FD). Results: Forty-three eyes of 27 patients were included. The mean extension ratio of EFI SS-OCTA compared to SS-OCTA without EFI and FA were 1.97 ± 0.02 and 0.85 ± 0.01. The mean extension of non-perfused areas with EFI SS-OCTA (34.22 ± 33.4 mm2) was significantly higher than SS-OCTA without EFI (20.46 ± 18.70 mm2), and with FA (27.55 ± 4.4 mm2). The mean VD and FD of EFI SS-OCTA were significantly different compared to SS-OCT without EFI. Conclusions: EFI SS-OCTA captured larger areas than SS-OCTA without EFI and FA. OCTA in a single shot is able to obtain more information of the retina without the use of montage techniques. Despite the determination of retinal ischemia seems to be easier and more accurate using EFI SS-OCTA, FA offers more details of the perfusion status of the retina. [ABSTRACT FROM AUTHOR]

Introduction: Half of all hypertensive individuals have inadequately-controlled BP because monitoring methods are ineffective. This single centre study examined consecutive subjects undergoing 24 hour BP measurements for clinic and ambulatory BP levels, and for end-organ damage (retinal microvascular abnormalities and left ventricular hypertrophy, LVH, > 1.1 cm). Retinal images were graded for microvascular retinopathy (Wong and Mitchell classification), and vessel calibre using a semiautomated method. Features were compared using chi-squared, Fisher’s exact or the student’s t test. Methods: One hundred and thirty-one individuals (59 male, 45.0%, mean age 61.7 ± 14.5 years) were studied. Ninety-nine (76.2%) had a clinic BP ≥ 140/90 mm Hg, 84 (64.6%) had a mean awake systolic BP ≥ 135 mm Hg, 100 (76.9%) had a mean sleeping systolic BP ≥ 120 mm Hg, and 100 (76.2%) had abnormal nocturnal BP dipping patterns. Sixty-nine individuals had undergone echocardiography and 23 (33.3%) had LVH. Results: All participants had a mild (88.5%) or moderate (11.5%) microvascular retinopathy. Moderate microvascular retinopathy was found in 86.7% of those with a mean awake systolic BP ≥135 mm Hg (p = 0.058) but was not associated with other abnormal BP measurements, abnormal dipping patterns or LVH. However retinal arteriole calibre was reduced in subjects with a mean 24 hour awake systolic BP ≥ 135 mm Hg (p = 0.05). Retinal arteriole calibre was smaller in subjects with LVH (128.1 ± 13.5 μm compared with 137.6 ± 14.1 μm in normals, p = 0.014). Venular calibre was also less in subjects with LVH (185.4 ± 24.6 μm compared with 203.0 ± 27.2 μm in normals, p = 0.016). Arteriole narrowing predicted an increased risk of LVH (AUC 0.69, 95%CI 0.55 to 0.83) that was comparable with 24 hour systolic BP ≥130 mm Hg (AUC 0.68, 95%CI 0.53 to 0.82) and mean awake systolic BP ≥135 mm Hg (AUC 0.68, 95%CI 0.54 to 0.83). Conclusions: This study suggests that retinal arteriole narrowing may be equally accurate in predicting LVH as any clinic or ambulatory BP measurement. The convenience and accuracy of microvascular calibre measurement mean that it should be investigated further for a role in routine hypertension assessment and monitoring. [ABSTRACT FROM AUTHOR]

Angiography by Optical Coherence Tomography (OCT-A) is a non-invasive retinal imaging modality of recent appearance that allows the visualization of the vascular structure at predefined depths based on the detection of the blood movement through the retinal vasculature. In this way, OCT-A images constitute a suitable scenario to analyze the retinal vascular properties of regions of interest as is the case of the macular area, measuring the characteristics of the foveal vascular and avascular zones. Extracted parameters of this region can be used as prognostic factors that determine if the patient suffers from certain pathologies (such as diabetic retinopathy or retinal vein occlusion, among others), indicating the associated pathological degree. The manual extraction of these biomedical parameters is a long, tedious and subjective process, introducing a significant intra and inter-expert variability, which penalizes the utility of the measurements. In addition, the absence of tools that automatically facilitate these calculations encourages the creation of computer-aided diagnosis frameworks that ease the doctor’s work, increasing their productivity and making viable the use of this type of vascular biomarkers. In this work we propose a fully automatic system that identifies and precisely segments the region of the foveal avascular zone (FAZ) using a novel ophthalmological image modality as is OCT-A. The system combines different image processing techniques to firstly identify the region where the FAZ is contained and, secondly, proceed with the extraction of its precise contour. The system was validated using a representative set of 213 healthy and diabetic OCT-A images, providing accurate results with the best correlation with the manual measurements of two experts clinician of 0.93 as well as a Jaccard’s index of 0.82 of the best experimental case in the experiments with healthy OCT-A images. The method also provided satisfactory results in diabetic OCT-A images, with a best correlation coefficient with the manual labeling of an expert clinician of 0.93 and a Jaccard’s index of 0.83. This tool provides an accurate FAZ measurement with the desired objectivity and reproducibility, being very useful for the analysis of relevant vascular diseases through the study of the retinal micro-circulation. [ABSTRACT FROM AUTHOR]

In the present study, we examined the causes and the prevalence of avoidable blindness and visual impairment, as well as the prevalence of diabetic retinopathy in individuals aged ≥50 years in Costa Rica, in order to provide baseline data for the initial planning and monitoring of ongoing blindness intervention programs. The assessment was based on the standardized methodology of the Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy, a population-based survey for blindness and visual impairment. From 3,255 eligible subjects, 76.6% were examined. The adjusted prevalence of bilateral blindness [presenting visual acuity (VA) in the better eye of less than 3/60] was 1.7% (95% confidence interval, 1.2%–2.2%), with avoidable causes (treatable and preventable) accounting for 68.8% of cases. The main causes of blindness were cataract (52.1%), glaucoma (6.3%), and diabetic retinopathy (6.3%); these data were similar to those for other neighboring countries. Cataract surgical coverage (CSC) in the survey area was estimated as 88.9% for individuals with blindness (VA, <3/60), 76.6% for those with a VA of <6/60, and 60.3% for those with a VA of <6/18. The most common barriers against cataract surgery in individuals with a best-corrected VA of ≤6/60 included “need not felt” (48.8%) and “fear” (14.6%). Among individuals with a past history of cataract surgery, only 57.1% showed a “good” or “very good” outcome (VA, ≥6/18). Finally, 23.5% individuals with known or newly diagnosed diabetes showed retinopathy and/or maculopathy, with 6.2% exhibiting sight-threatening diabetic retinopathy (proliferative retinopathy, referable maculopathy, or both). Our findings indicate the need to overcome barriers against surgery for cataract, which is the main cause of avoidable blindness, to increase CSC, and to improve surgical outcomes. Moreover, improved methods for diabetic retinopathy screening can ensure prompt identification of patients with a risk of blindness. Glaucoma screening is also necessary for areas with a high prevalence. [ABSTRACT FROM AUTHOR]

This study aimed to determine the natural course of patent ductus arteriosus (PDA) with noninterventional conservative management and whether the presence and/or prolonged duration of hemodynamically significant (HS) PDA increased the risk of mortality and morbidities in extremely preterm (EPT) infants. We retrospectively reviewed the medical records of EPT infants born at 23–28 weeks of gestation (n = 195) from January 2011 to June 2014, when PDA was managed with noninterventional conservative treatment. We stratified infants into three subgroups of 23–24, 25–26, and 27–28 weeks and analyzed the prevalence and natural evolution of HS PDA, defined as ventilator dependency and PDA size ≥2 mm. Multivariate regression analyses determined if the presence and/or prolonged duration of HS PDA increased the risk for mortality and/or morbidities. The overall incidence of HS PDA was 57% (111/195) at the end of the first postnatal week. In subgroup analyses, infants with 23–24 weeks of gestation had the highest incidence (93%, 50/54), with 64% (47/74) for 25–26 weeks and 21% (14/67) for 27–28 weeks. Six (5%) of 111 infants with HS PDA were discharged without ductus closure, 4 had spontaneous PDA closure on follow up, and device closure was performed for 2 infants. In the multivariate analyses, the presence or prolonged duration (per week) of HS PDA was not associated with the risk of mortality and/or morbidities. Spontaneous closure of HS PDA was mostly achieved, even in EPT infants, with a noninterventional conservative approach. In conclusion, our data showed the incidence and natural course of HS PDA in EPT infants and suggested that the presence or prolonged duration of HS PDA might not increase the rate of mortality or morbidities. [ABSTRACT FROM AUTHOR]

Aim: To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database. Methods: We identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in patients with type-2 diabetes. The main outcome was the hospitalization for HHF. Hazard ratios for HHF by type of second-line glucose-lowering medication were estimated by Cox-proportional hazard models. Sex, age, duration of MET monotherapy, Charlson Comorbidity Index and additional comorbidities, and calendar year were controlled as potential confounders. Results: The observed numbers (rate per 100,000 person-years) of HHF events were 1,129 (658) for MET+SU users, 710 (455) for MET+DPP-4i users, and 110 (570) for MET+TZD users. Compared to that for MET+SU users (reference group), the adjusted hazard ratios for HHF events were 0.76 (95% confidence interval 0.69–0.84) for MET+DPP-4i users and 0.96 (95% confidence interval 0.79–1.17) for MET+TZD users. Conclusion: DPP-4i as an add-on therapy to MET may lower the risks of HHF compared with SU. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders. Methods: This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline’s criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates. Results: Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2–3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1–7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1–0.7) and need for surfactant (OR = 0.5, CI: 0.2–0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2–3 only, RC = 6.5 days, CI: 2–11). No other outcome was affected. Conclusions: IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a common neurovascular complication of type 1 diabetes. Current therapeutics target neovascularization characteristic of end-stage disease, but are associated with significant adverse effects. Targeting early events of DR such as neurodegeneration may lead to safer and more effective approaches to treatment. Two independent prospective clinical trials unexpectedly identified that the PPARα agonist fenofibrate had unprecedented therapeutic effects in DR, but gave little insight into the physiological and molecular mechanisms of action. The objective of the present study was to evaluate potential neuroprotective effects of PPARα in DR, and subsequently to identify the responsible mechanism of action. Here we reveal that activation of PPARα had a robust protective effect on retinal function as shown by Optokinetic tracking in a rat model of type 1 diabetes, and also decreased retinal cell death, as demonstrated by a DNA fragmentation ELISA. Further, PPARα ablation exacerbated diabetes-induced decline of visual function as demonstrated by ERG analysis. We further found that PPARα improved mitochondrial efficiency in DR, and decreased ROS production and cell death in cultured retinal neurons. Oxidative stress biomarkers were elevated in diabetic Pparα-/- mice, suggesting increased oxidative stress. Mitochondrially mediated apoptosis and oxidative stress secondary to mitochondrial dysfunction contribute to neurodegeneration in DR. Taken together, these findings identify a robust neuroprotective effect for PPARα in DR, which may be due to improved mitochondrial function and subsequent alleviation of energetic deficits, oxidative stress and mitochondrially mediated apoptosis. [ABSTRACT FROM AUTHOR]

Aims: To study if retinopathy increases the risk of stroke recurrence in stroke patients with type 2 diabetes. Also, to study if stroke patients with type 2 diabetes have an increased risk of stroke recurrence compared to non-diabetics and if stroke patients with type 2 diabetes, regardless of retinopathy, have a higher incidence of carotid stenosis. Also, to study if stroke patients with type 2 diabetes retinopathy have increased incidence of carotid stenosis. Methods: We included 445 patients with type 2 diabetes mellitus and a matched control group of 445 patients without diabetes, who had all suffered their first stroke or TIA. Information on retinopathy, risk factors and stroke recurrence were obtained from registers and medical records. Results: Retinopathy did not increase the risk of stroke recurrence in diabetes patients, HR 0.89 (0.51–1.53), p = 0.67. The risk of stroke recurrence was not increased in diabetics compared to non-diabetes. Diabetes patients had an increased prevalence of carotid stenosis compared to non-diabetics, 1.69 (1.15–2.48), p = 0.008. The prevalence of carotid stenosis in diabetics with retinopathy was not increased compared to diabetics without retinopathy. Conclusion: Retinopathy is not a predictor of stroke recurrence or carotid stenosis in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare repeatability between SS-OCT and SD-OCT for measurement of macular, macular retinal nerve fiber (mRNFL), and ganglion cell-inner plexiform layer (GC-IPL) thickness in various retinal diseases. Methods: One hundred and fourteen eyes of 114 subjects were investigated. Seventy-eight eyes with retinal disease and 36 normal eyes underwent two consecutive measurements of macular, mRNFL, and GC-IPL thickness using SS-OCT and SD-OCT. The data were obtained using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. The eyes with retinal diseases were divided into three subgroups according to central macular thickness (CMT) for analysis. The intraclass correlation coefficient (ICC) was calculated to determine the repeatability of OCT device. Results: In normal eyes, both OCT devices showed excellent repeatability of macula, mRNFL, and GC-IPL thickness measurements with high ICCs in all ETDRS subfields. In eyes with retinal disease, although SS-OCT showed better repeatability for inner retinal thickness measurements than SD-OCT, the overall ICCs were lower than those in normal eyes. In subgroup analysis, the ICCs in the low CMT group were lower than those in the normal and high CMT groups, particularly when using SD-OCT. Conclusions: Both OCT devices had comparable repeatability for retinal thickness measurement in normal eyes and eyes with retinal disease. However, the possibility of measurement error should be considered in eyes with a thin and atrophic retina. [ABSTRACT FROM AUTHOR]

Studies have demonstrated the adverse effects of smoking on the risk of microvascular complications; however, few have also examined the potential mediating effects of glycemic control. Using data from the Diabetes Control and Complications Trial (DCCT 1983–1993), we describe the acute and long-term risks of smoking on glycemic control and microvascular complications in a well-characterized cohort of participants with type 1 diabetes. The DCCT recorded self-reported smoking behaviors, glycemic exposure based on HbA1c, and complications status. Generalized linear mixed models were used to assess whether time-dependent measurements of smoking predict HbA1c levels. Cox proportional hazard models were used to assess time-dependent smoking exposures as predictors of retinopathy and nephropathy. During a mean of 6.5 years of follow-up, current smokers had consistently higher HbA1c values and were at a higher risk of retinopathy and nephropathy compared with former and never smokers. These risk differences were attenuated after adjusting for HbA1c suggesting that the negative association of smoking on glycemic control is partially responsible for the adverse association of smoking on the risk of complications in type 1 diabetes. These findings support the potential for a beneficial effect of smoking cessation on complications in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Most infants born before 30 weeks gestational age (GA) develop respiratory distress syndrome soon after birth. Methods of surfactant administration that avoid ventilation have been recently introduced. The aim of this study was to evaluate the impact of implementing a new procedure of less invasive surfactant administration (LISA) and determine whether it is associated with an improvement in respiratory outcome. Methods: This single center cohort quality improvement study analyzed preterm infants born before 30 weeks GA between May 2010 and April 2016. Changes in health care practices and respiratory outcomes following the implementation of a LISA, i.e. the administration of surfactant through a thin catheter, were analyzed using quality control charts. Then, the effect of LISA on respiratory outcome was assessed by propensity score matching and logistic regression weighted by the inverse of the propensity score. Results: During the study period, 379 infants were included. Of those that were not intubated at ten minutes of life, 129 received surfactant and were ventilated for one hour or more (InVent), 127 received LISA, five received surfactant with tracheal mechanical ventilation for less than one hour (InSurE), and 55 were only treated with nasal continuous positive pressure during the first hour of neonatal care (nCPAP). Quality-chart analysis revealed rapid implementation of the method with a concomitant decrease in required ventilation. LISA was associated with fewer tracheal ventilation days and a lower incidence of supplemental oxygen on day 28. When controlling for the propensity to be exposed or not to LISA, this procedure was not associated with a lower risk of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Conclusion: In this study, the successful implementation of the new method was associated with lower rates of mechanical ventilation, but without a significant reduction of grade I/II/III BPD or death. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans. Methods: A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey’s test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis. Results: SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81μm vs 284.53±56.45μm, p<0.001), and showed an ascending trend with worsening of DR, though this difference was not statistically significant [mild non-proliferative diabetic retinopathy (NPDR) = 304.33±40.39μm, moderate NPDR = 327.81±47.39μm, severe NPDR = 357.72±62.65μm, proliferative DR (PDR) = 334.59±47.4μm, p-0.09]. CVI was significantly decreased in DME with DR eyes as compared to controls (63.89±1.89 vs 67.51±2.86, p<0.001). CVI was also significantly decreased with worsening DR (mild NPDR = 66.38±0.3, moderate NPDR = 65.28±0.37, severe NPDR = 63.50±0.47, PDR = 61.27±0.9, p<0.001). Conclusion: SFCT and CVI are dynamic parameters that are affected by DME. Unlike CVI, SFCT is also affected by ocular and systemic factors like edema and hypertension. CVI may be a more accurate surrogate marker for DME and DR and can potentially be used to monitor the progression of DR. [ABSTRACT FROM AUTHOR]

Purpose: To compare the surgical outcomes between pre- and full-term patients with exotropia and to examine the factors associated with surgical outcomes. Methods: This retrospective study included 48 pre- and 432 full-term patients with basic-type exotropia who underwent unilateral or bilateral lateral rectus muscle (ULR or BLR) recession. Preoperative characteristics and surgical outcomes were compared between the pre- and full-term infants. Additionally, factors affecting the surgical outcomes were evaluated in all patients. Results: The preoperative characteristics were significantly different between the pre- and full-term groups in terms of neurodevelopmental disabilities (p = 0.020). There were no significant differences between the pre- and full-term groups in terms of the success, overcorrection, and recurrence rates after the mean follow-up period of 34.6 ± 13.9 months (p = 0.697). The major cause of surgical failure was recurrence in both groups. Pre-term birth was not a risk factor for overcorrection and recurrence. However, regardless of the pre- or full-term birth status, the presence of neurodevelopmental disabilities significantly affected final overcorrection (p = 0.004). Conclusions: Pre-term patients with exotropia showed similar surgical outcomes to full-term controls. The presence of neurodevelopmental disabilities was a risk factor for final overcorrection. [ABSTRACT FROM AUTHOR]

We aimed to test the hypothesis that determinants of the perinatal clinical exposome related to the underlying etiology of premature birth (PTB) impact differently on select neonatal outcomes. We conducted a prospective longitudinal study of 377 singleton preterm neonates [gestational age (GA) at birth: 23–34 weeks] separated into three distinct contemporaneous newborn cohorts: i) spontaneous PTB in the setting of intra-amniotic infection/inflammation (yes-IAI, n = 116); ii) spontaneous PTB in the absence of IAI (no-IAI, n = 130), and iii) iatrogenic PTB for preeclampsia (iPTB-PE, n = 131). Newborns (n = 372) were followed until death or discharge. Amniotic fluid defensins 1&2 and calgranulins A&C were used as biomarkers of IAI. An algorithm considering cord blood interleukin-6 (IL-6) and haptoglobin (Hp switch-on) was used to assess fetal exposure to IAI. Intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), early-onset neonatal (EONS) and late-onset (LOS) sepsis, death. Independent risk factors for adverse outcomes were: i) IVH (n = 53): histologic chorioamnionitis, GA, fetal growth restriction, male sex, Hp switch-on; ii) PVL (n = 11): cord blood IL-6; iii) NEC (n = 25), GA; iv) BPD (n = 53): ventilator support, need for surfactant, GA; v) ROP (n = 79): ventilator support, Hp switch-on, GA; vi) fetal and neonatal death (n = 31): GA, amniotic fluid IL-6; vii) suspect EONS (n = 92): GA, Hp switch-on; viii) LOS (n = 81): GA. Our findings are applicable to pregnancies delivered between 23 and 34 weeks’ gestation in the setting of IAI and PE, and suggest that GA and inflammatory intrauterine environment play key roles in occurrence of IVH, PVL, ROP, death, EONS and LOS. Postnatal determinants seem to play major role in NEC and BPD. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a disease which is widely diagnosed using (colour fundus) images. Efficiency and accuracy are critical in diagnosing DR as lack of timely intervention can lead to irreversible visual impairment. In this paper, we examine strategies for scrutinizing images which affect diagnostic performance of medical practitioners via an eye-tracking study. A total of 56 subjects with 0 to 18 years of experience participated in the study. Every subject was asked to detect DR from 40 images. The findings indicate that practitioners use mainly two types of strategies characterized by either higher dwell duration or longer track length. The main findings of the study are that higher dwell-based strategy led to higher average accuracy (> 85%) in diagnosis, irrespective of the expertise of practitioner; whereas, the average obtained accuracy with a long-track length-based strategy was dependent on the expertise of the practitioner. In the second part of the paper, we use the experimental findings to recommend a scanning strategy for fast and accurate diagnosis of DR that can be potentially used by image readers. This is derived by combining the eye-tracking gaze maps of medical experts in a novel manner based on a set of rules. This strategy requires scrutiny of images in a manner which is consistent with spatial preferences found in human perception in general and in the domain of fundus images in particular. The Levenshtein distance-based assessment of gaze patterns also establish the effectiveness of the derived scanning pattern and is thus recommended for image readers. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between baseline number of hyperreflective foci (HF) on spectral domain optical coherence tomography (SD-OCT) in patients with diabetic macular edema (DME), as well as the dynamics of HF during treatment with anti-vascular endothelial growth factor (VEGF), and treatment response. Methods: We evaluated patients diagnosed with DME scheduled for treatment with intravitreal bevacizumab. Eyes were classified as adequate or insufficient treatment responders based on logMAR visual acuity improvement and central retinal thickness (CRT) decrease after three consecutive injections. Associations between number of HF at baseline and treatment response, the change in HF over the course of treatment, and the distribution of HF within the retinal layers were evaluated. Results: In 54 eyes of 41 patients, mean number of HF and CRT decreased after intravitreal treatment with bevacizumab (p = 0.002 and p<0.001 respectively). Decrease in CRT after 3 months was independently associated with a higher number of HF at baseline (estimated effect -2.61, 95% CI [-4.42–-0.31], p = 0.006). Eyes with adequate treatment response presented with more HF at baseline (OR 1.106, 95% CI [1.012–1.210], p = 0.030) than eyes with insufficient treatment response. Most HF were located within the inner retinal layers, and decrease of HF was mostly due to a decrease of inner retinal HF. Conclusions: In patients with DME treated with anti-VEGF, higher baseline numbers of HF have predictive value for treatment response in terms of visual acuity improvement and CRT decrease after 3 months. In addition, HF were responsive to anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

In France, secondary care hospitals encounter difficulties to adhere to retinopathy of prematurity (ROP) screening guidelines. Our objective was to assess the effectiveness and efficacy of a tele-expertise program for ROP screening in neonatal intensive care units without on-site ophthalmologists. We evaluated the impact of a tele-expertise program funded by the Paris Region Health Authority in a secondary care center general hospital of the Paris Region (CHSF), where there was previously no on-site ophthalmologist. We performed an observational, controlled before-after study, with a university tertiary care center with on-site ophthalmologists (Port-Royal) as the control group. Recruitment and data collection for both periods took place from 1 January 2012 to 31 December 31 2012, and from 1 January 2014 to 31 March 2015. The primary endpoint was the percentage of compliance with screening guidelines, secondary endpoints included pain scores and costs. Over the two periods, at total of 351 infants were recruited in the CHSF. Implementation of the tele-expertise resulted in an absolute +57.3% increase in the proportion of examinations realized in accordance with guidelines (3.8% during the "before" period and 61.1% during the "after" period, p<0.001). As compared with the control group, the proportion of infants appropriately screened improved (57.5% versus 43.1%, p = 0.002); median pain score on the acute pain rating scale for neonates during examination was significantly higher (median score 5.5/10, range [2.5–5.7] versus 2.0/10, range [1.0–3.1], p = 0.002). Screening rates in the control group remained unchanged. The average cost per examination increased from €337 in the "before" period to €353 in the "after period" in the tele-expertise group. The implementation of tele-expertise for ROP screening in the CHSF medical center resulted in a major improvement of access to care with a small cost increase. The issue of pain control during examination with tele-expertise should be further addressed. [ABSTRACT FROM AUTHOR]

Purpose: To compare macular and peripapillary vessel density values calculated on optical coherence tomography angiography (OCT-A) images with different algorithms, elaborate conversion formula, and compare the ability to discriminate healthy from affected eyes. Methods: Cross-sectional study of healthy subjects, patients with diabetic retinopathy, and glaucoma patients (44 eyes in each group). Vessel density in the macular superficial capillary plexus (SCP), deep capillary plexus (DCP), and the peripapillary radial capillary plexus (RCP) were calculated with seven previously published algorithms. Systemic differences, diagnostic properties, reliability, and agreement of the methods were investigated. Results: Healthy eyes exhibited higher vessel density values in all plexuses compared to diseased eyes regardless of the algorithm used (p<0.01). The estimated vessel densities were significantly different at all the plexuses (p<0.0001) as a function of method used. Inter-method reliability and agreement was mostly poor to moderate. A conversion formula was available for every method, except for the conversion between multilevel and fixed at the DCP. Substantial systemic, non-constant biases were evident between many algorithms. No algorithm outperformed the others for discrimination of patients from healthy subjects in all the retinal plexuses, but the best performing algorithm varied with the selected plexus. Conclusions: Absolute vessel density values calculated with different algorithms are not directly interchangeable. Differences between healthy and affected eyes could be appreciated with all methods with different discriminatory abilities as a function of the plexus analyzed. Longitudinal monitoring of vessel density should be performed with the same algorithm. Studies adopting vessel density as an outcome measure should not rely on external normative databases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the repeatability, the reproducibility and the agreement of foveal avascular zone (FAZ) measurements using three different optical coherence tomography angiography (OCT-A) devices. Procedures: This prospective study included 24 eyes of 24 healthy volunteers. OCT-A imaging was performed using RTVue XR Avanti, Canon OCT-HS100 and Spectralis OCT-A. Repeated measurements were performed under the same conditions on two separate days, and the area of the FAZ was determined and analyzed using the above devices. Results: All three devices showed a high ICC and there was no significant difference between the ICCs (pairwise comparison) of the three devices (Optovue–Canon (p = 0.66); Canon–Heidelberg (p = 0.21); Heidelberg–Optovue (p = 0.37). Agreement analysis of the three devices revealed a significant elevation of FAZ area values with the Heidelberg device and a slight underestimation of the FAZ area with the Canon device. Nevertheless, overall we found a high level of agreement between all of the three devices (ICC ≥ 0.958 (0.905–0.982)). Conclusions: Good reproducibility and repeatability were observed for all three devices. However, the agreement analysis revealed slight, but significant differences, which might limit alternating use of these devices for clinical research and follow-up examinations. [ABSTRACT FROM AUTHOR]

The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) is difficult to establish, because CA-exposed and CA-unexposed infants frequently present different baseline characteristics. We performed an updated systematic review and meta-analysis of studies reporting on the association between CA and ROP. We searched PubMed and EMBASE for relevant articles. Studies were included if they examined preterm or very low birth weight (VLBW, <1500g) infants and reported primary data that could be used to measure the association between exposure to CA and the presence of ROP. Of 748 potentially relevant studies, 50 studies met the inclusion criteria (38,986 infants, 9,258 CA cases). Meta-analysis showed a significant positive association between CA and any stage ROP (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.74). CA was also associated with severe (stage ≥3) ROP (OR 1.63, 95% CI 1.41 to 1.89). Exposure to funisitis was associated with a higher risk of ROP than exposure to CA in the absence of funisitis. Additional meta-analyses showed that infants exposed to CA had lower gestational age (GA) and lower birth weight (BW). Meta-regression showed that lower GA and BW in the CA-exposed group was significantly associated with a higher risk of ROP. Meta-analyses of studies with data adjusted for confounders could not find a significant association between CA and ROP. In conclusion, our study confirms that CA is a risk factor for developing ROP. However, part of the effects of CA on the pathogenesis of ROP may be mediated by the role of CA as an etiological factor for very preterm birth. [ABSTRACT FROM AUTHOR]

Purpose: Ellipsoid zone (EZ) and outer retinal integrity are strongly linked to visual prognosis, but quantitative normative data is lacking. This study evaluates the EZ, outer retina, and inner retina in eyes without macular disease across a wide age spectrum. Methods: An IRB-approved study was performed for eyes without macular pathology undergoing Spectral Domain Optical Coherence Tomography (SD-OCT) scans on the Cirrus HD-OCT system (Carl Zeiss Meditec, Oberkochen, Germany). Scans were analyzed using a previously described automated EZ mapping tool with line-by-line manual verification. Segmentation included internal limiting membrane (ILM), outer nuclear layer/Henle fiber layer complex (ONL/HFL), EZ, and the retinal pigment epithelium (RPE). The output included metrics for the inner retina (ILM-OPL/HFL), outer retina (ONL/HFL-RPE), EZ-RPE area and volume, and en face EZ mapping. EZ-RPE attenuation on en face mapping was defined as EZ-RPE thickness < 20 um, and total attenuation was 0 um. Imaging parameters were assessed for the group and compared to age, sex, visual acuity and spherical equivalent. Results: 167 eyes from 167 subjects were included. Mean age was 49.7 years (range 10–84 years). The mean foveal retinal thickness was 200.58 ± 19.22 um. Mean inner retinal thickness was 21.47 ± 13.60 um. Mean outer retinal thickness was 179.11 ± 18.52 um. Mean EZ-RPE thickness was 50.58 ± 6.01um. The mean EZ-RPE volume was 1.20 ± 0.10 mm3. Mean EZ attenuation percentage per macular map area was 0.87% ± 1.13% and mean percentage total attenuation was 0.12% ± 0.14%. Total and inner retinal thickness metrics decreased with age. Mean outer retinal thickness increased with age. EZ-RPE parameters were unchanged with age. However, EZ attenuation was negatively correlated with age. Conclusion: This study provides important information for inner and outer retinal parameters. Future research on quantitative EZ integrity can utilize this data for comparison. [ABSTRACT FROM AUTHOR]

Purpose: Systemic inflammation is potentially associated with ocular diseases such as late age-related macular degeneration (AMD). Using the serum concentration of high-sensitive C-reactive protein (hs-CRP) as surrogate of systemic inflammation, we examined potential associations between the serum hs-CRP concentration and the presence and degree of eye diseases. Methods: The population-based Beijing Eye Study included 3468 Chinese individuals. The study participants underwent a standardized interview and a detailed ophthalmic examination. The serum concentration of hs-CRP was determined. Results: Out of 3468 participants, 2452 (70.7%) individuals (mean age:63.4±9.4 year; range:50–91 years) had hs-CRP measurements (mean:1.96±4.07mg/L). In multivariate analysis, higher serum concentration of hs-CRP was significantly (regression coefficient r: 0.21) associated with a higher level of diabetic retinopathy (P = 0.007; standardized regression coefficient beta:0.06; non-standardized regression coefficient B:1.35; 95% confidence interval (CI):0.37,2.22) and polypoidal choroidal vasculopathy (P = 0.002;beta:0.06;B:6.22;95%CI:2.24,10.2) after adjusting for higher serum concentration of high-density lipoproteins (P<0.001;beta:-0.12;B:-1.31;95%CI:-1.77,-0.85), higher body mass index (P = 0.01;beta:0.06;B:0.06;95%CI:0.01, 0.11), lower level of education (P = 0.04;beta:-0.06;B:-0.22;95%CI:-0.42,-0.02), lower cognitive function score (P = 0.01;beta:-0.07;B:-0.08;95%CI:-0.13,-0.02). If the presences of other ocular diseases were added to the model, the presence of glaucoma (P = 0.99), open-angle glaucoma (P = 0.80), angle-closure glaucoma (P = 0.67), pseudoexfoliation (P = 0.18), nuclear cataract (P = 0.30), cortical cataract (P = 0.15), subcapsular cataract (P = 0.59), retinal vein occlusions (P = 0.33), central serous choroidopathy (P = 0.44), early stage of age-related macular degeneration (AMD) (P = 0.46), intermediate stage of AMD (P = 0.20) and late stage of AMD (P = 0.91) including geographic atrophy (P = 0.60) or neovascular AMD (P = 0.68) were not significantly associated with the serum concentration of hs-CRP. Conclusions: In Chinese aged 50+ years, higher serum concentration of hs-CRP was significantly associated with a higher level of diabetic retinopathy and higher frequency of polypoidal choroidal vasculopathy. Other major ocular disorders, namely glaucoma including open-angle glaucoma and angle-closure glaucoma, pseudoexfoliation, nuclear, cortical or subcapsular cataract, retinal vein occlusions, central serous choroidopathy, early, intermediate or late stage of AMD including geographic atrophy, were not significantly associated with hs-CRP serum concentrations. It suggests that these diseases, in contrast to diabetic retinopathy and polypoidal choroidal vasculopathy, were not associated with a major systemic inflammatory component. [ABSTRACT FROM AUTHOR]

The critical need to emphasize preterm infant follow-up after neonatal intensive care unit (NICU) discharge assures early identification of and intervention for neurodevelopmental disability. The aims of this study were to observe the follow-up rates in high-risk follow-up clinics, and analyze factors associated with non-compliance to follow-up among very low birth weight (VLBW) infants. The data was prospectively collected for 3063 VLBW infants between January 2013 and December 2014 from 57 Korean neonatal network (KNN) centers at a corrected age of 18–24 months. Correlations among demographic data, clinical variables, and neonatal intensive care unit (NICU) volume (divided into 4 quartiles) with the occurrence of non-compliance were analyzed. The overall follow-up rate at the corrected age of 18–24 month was 65.4%. The follow-up rates were inversely related to birth weight and gestational age. Apgar score, hospital stay, maternal age, and maternal education were significantly different between the compliance and non-compliance groups. The follow-up rate was higher for mothers with chorioamnionitis, abnormal amniotic fluid, multiple pregnancy, and in vitro fertilization. Infants with respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus ligation, periventricular leukomalacia, and retinopathy of prematurity were more common in the compliance group. Follow-up rates showed significant differences according to NICU volume. Using multivariate logistic regression, high birth weight, low NICU volume, siblings, foreign maternal nationality and high 5 min APGAR scores were significant independent factors associated with the non-compliance of VLBW infants for follow-up at 18–24 months of age. This is the first nation-wide analysis of follow-up for VLBW infants in Korea. Understanding factors associated with failure of compliance could help improve the long-term follow-up rates and neurodevelopmental outcomes through early intervention. [ABSTRACT FROM AUTHOR]

Purpose: To determine aqueous cytokines association with response to intravitreal bevacizumab (IVB) injection in diabetic macular edema (DME). Method: We compared the concentrations of IL (interleukin)-1β, IL-2, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor of 64 naïve DME patients with those of 13 cataract patients. Factors associated with central subfield thickness (CST) in DME patients were identified. DME patients were then subgrouped in terms of responsiveness to three IVB injections; cytokine concentrations were compared, and factors associated with responsiveness were identified. Results: Levels of IL-2, IL-8, PlGF, and VEGF were significantly elevated in DME patients (p = 0.007, p < 0.001, p < 0.001, and p = 0.004 respectively). Regression analysis showed that the preoperative CST was associated with the preoperative best-corrected visual acuity and the aqueous IL-10 level (p < 0.001, p = 0.006, respectively). Of the 64 DME patients, 28 (43.75%) exhibited either CST < 300 μm or reduction in CST ≥ 50 μm after three consecutive IVB injections. On sub-group analysis, the mean IL-8 concentration was higher in the refractory group than in the responsive group, and multivariate logistic regression analysis showed that the IL-8 was the only factor associated with responsiveness (OR = 0.95, p = 0.017). Conclusions: The IL-8 concentration in the aqueous humor was associated with responsiveness to IVB in DME patients. [ABSTRACT FROM AUTHOR]

Introduction: Parents have a major impact on the outcome of health care of preterm infants. Parents’ engagement in meaningful activities could have an impact on their own health and wellbeing and therefore be relevant in neonatal intensive care. The aim of this study was to explore meaningful activities of parents of very low birth weight (VLBW) preterm infants with the purpose to further the understanding of their clinical relevance and to foster their consideration in clinical practice and research of neonatal intensive care. Methods: A total of 36 parents of preterm infants born prior to complete 37 weeks of gestation with VLBW (≤1.500 grams) were asked to participate in a focus group interview. Interview transcripts were used to analyse the content of the focus group interviews using meaning condensation method by Steinar Kvale. Results: Thirty-six parents participated in a total of twelve focus groups. Parents reported that the meaning of certain activities changed due to preterm birth. Meaningful activities, like bathing the baby and gardening, could foster a transition from a feeling of parental immaturity to a feeling of maturity, following health care instructions to possessing health care skills, and a functioning-only state to a balance of activities. Conclusions: In neonatal intensive care, nurses contribute to delivering parental education and thereby facilitate experiences of being a mature parent and of possessing health care skills. Occupational therapy could be used to help re-engage in meaningful activities and maintain a balance of activities in parents of VLBW preterm infants. [ABSTRACT FROM AUTHOR]

This study explored whether cataract surgery precipitates diabetic retinopathy (DR) development in diabetic patients without previous DR. Patients with the diagnosis of type II diabetes but without DR were selected from the Longitudinal Health Insurance Database 2000. Patients who received cataract surgery between January 1, 2000, and December 31, 2010, were included in the case group, and the control group was matched to the case group by age, sex, and index year. The postoperative incidence rates of nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) were the main outcomes studied and were adjusted by age, sex, comorbidities, and statin, fibrate, angiotensin-converting-enzyme inhibitor (ACEI), oral hypoglycemic agents (OHA), and insulin use. In our cohort, patients who had dyslipidemia and used statins were more likely to undergo cataract surgery. Among diabetic patients without previous DR, patients receiving cataract surgery had a higher risk of NDPR development (adjusted hazard ratio = 1.48, 95% confidence interval = 1.15–1.91). No statistical difference was observed in PDR or DME development between operative and nonoperative groups. In additional stratified analyses, female sex, older age, comorbidities, surgery within 5 years, statin ACEI, OHA, and insulin use increased the risk of NPDR development. In an adjusted Cox regression model, cataract surgery, OHA and insulin use were found to be risk factors for NPDR development. Cataract surgery with complications increased post-operative risks for NPDR were even higher, and the significant influence from cataract surgery persisted 5 years after surgery. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic accuracy of a digital fundus photographic system that consists of taking fundus photographs by a trained technician using a RetCam® shuttle and interpreting fundus images by an expert to detect Retinotapthy of Prematurity requiring treatment (ROP-RT) which defined as type I ROP according to the Early Treatment for ROP study (ETROP). Materials and methods: One hundred infants were examined by (1) an expert ophthalmologist experienced in ROP care using indirect ophthalmoscopy; (2) digital wide-field imaging by a trained technician using a RetCam® shuttle and images were sent remotely for interpretation by two ophthalmologists experienced in ROP care (Reader A, and Reader B); and (3) local ophthalmologists using indirect ophthalmoscopy. The diagnostic acurracy consisting of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated. Agreement between all examiners and readers were evaluated. Results: A total of 100 infants (mean gestational age 31.1 weeks, mean birth weight 1,511.1 grams) participated in the study. Nine infants were classified as ROP-RT. Reader A and B had very good agreement in detection of ROP- RT (Kappa 1.00, 95% CI 1.00, 1.00). For reader A, diagnostic performance parameters (95% confidence intervals) for detecting ROP-RT were; sensitivity 100.0% (66.4, 100.0), specificity 97.8% (92.1, 99.7), PPV 81.8% (48.2, 97.7), NPV 100.0% (95.8, 100.0), LR+ 44.5 (11.3, 175.2), and LR- 0.1 (0.0, 0.8). For reader B these were; sensitivity 100.0% (66.4, 100.0), specificity 95.6% (89.0, 98.8), PPV 69.2% (38.6, 90.9), NPV 100.0% (95.8, 100.0), LR+ 22.5 (8.6, 58.6), LR- 0.1 (0.0, 0.8). No adverse events were reported. Conclusions: Diagnosis of ROP-RT from RetCam® images taken by trained technicians and evaluated remotely by an expert ophthalmologist had good diagnostic accuracy for screening purposes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the repeatability and reproducibility of retinal and choroidal thickness measured with Swept source Optical Coherence Tomography (SS-OCT) in eyes with Diabetic Macular Edema (DME). Methods: 42 DME eyes were imaged using SS-OCT standard Macular scanning protocols. Retinal and choroidal thickness were measured in the Total macular circle (TMC) and foveal central subfield (FCS) using device-integrated specific software. The coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were determined as a measure of repeatability and relative reliability within graders. Reproducibility was assessed using Bland-Altman plots and 95% limits of agreement (LoA) were determined as a measure of interobserver variability. Results: Intragrader CR of retinal and choroidal thickness were 8.37 and 12.20 microns for TMC and 22.24 and 32.40 microns for FCS, and intergrader 95% LoA were 7.37–8.69 and -27.2–27.71 microns for TMC and -34.21–41.93 and -30.46–24.84 for FCS, respectively. Retinal and choroidal thickness showed very good intraobserver reliability for both TMC and FCS (ICC 0.99, LoA 0.98–0.99 in all cases). Intraobserver and interobserver variability for retinal and choroidal thickness was not significantly different for TMC (p = 0.98 and p = 0.90, p = 0.98 and p = 0.91) or FCS (p = 0.97 and p = 0.85, p = 0.78 and p = 0.73), respectively. Conclusions: Retinal and choroidal thickness in DME eyes can be quantified with good reliability, repeatability and reproducibility using new OCT devices that incorporate swept source technology. The technical advantages of this technology may provide new insights in the understanding of the choroidal changes related with DME. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in colour vision following intravitreal injection of Dexamethasone implant (Ozurdex) in patients with diabetic macular oedema (DMO). Both red-green (RG) and yellow-blue (YB) chromatic sensitivity were assessed using the Colour Assessment & Diagnosis (CAD) test which isolates the use of colour signals and provides age-corrected, statistical limits for normal trichromats. To determine whether colour changes and visual acuity (VA) post-treatment relate to central sub-field retinal thickness (CST). Methods: Fourteen patients with DMO who were undergoing treatment with Ozurdex were recruited for this study. RG and YB colour thresholds were measured using the CAD test, best corrected visual acuity was assessed using the ETDRS chart and CST was measured using spectral domain optical coherence tomography (SD-OCT). All tests were performed monocularly at baseline and 24 weeks post injection. Results: All patients (n = 14 eyes), had significant loss of RG and YB chromatic sensitivity at baseline (p<0.05). The mean age was 56 ± 9.5 years. The age specific, monocular, upper normal limits for a 56 year old subject are 2.66 for RG and 2.85 for YB. In this study, the measured, pre injection thresholds (mean±SD) were 22.6 ± 11.3 for RG and 16.2 ± 3.76 for YB. There was significant improvement in RG threshold post injection (i.e., 19.2 ± 10.8 (p<0.05)). No significant changes were found in the YB thresholds with corresponding mean and range values of: 15.8 ± 4.6 (p = 0.23). CST pre-treatment was 542 ±135 μm. After treatment and by week 24 the CST values decreased to 435 ±127 μm. Conclusions: RG colour thresholds provide a sensitive measure of functional change in diabetic subjects with macular oedema. The YB system is damaged severely in the DMO patients studied and shows little or no recovery post treatment. The improvement in VA and particularly in RG colour vision correlate well with the measured decrease in CST. The results suggest that the improvement in the RG chromatic sensitivity can provide a useful biomarker for monitoring the efficacy of treatment in DMO. [ABSTRACT FROM AUTHOR]

Background: Diabetes and its complications are more common in American Indians and Alaska Natives (AI/AN) than other US racial/ethnic populations. Prior reports of diabetic retinopathy (DR) prevalence in AI/AN are dated, and research on diabetic macular edema (DME) is limited. This study characterizes the recent prevalence of DR and DME in AI/AN using primary care-based teleophthalmology surveillance. Methods: This is a multi-site, clinic-based, cross-sectional study of DR and DME. The sample is composed of AI /AN patients with diabetes (n = 53,998), served by the nationally distributed Indian Health Service-Joslin Vision Network Teleophthalmology Program (IHS-JVN) in primary care clinics of US Indian Health Service (IHS), Tribal, and Urban Indian health care facilities (I/T/U) from 1 November 2011 to 31 October 2016. Patients were recruited opportunistically for a retinal examination using the IHS-JVN during their regular diabetes care. The IHS-JVN used clinically validated, non-mydriatic, retinal imaging and retinopathy assessment protocols to identify the severity levels of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), DME, and sight threatening retinopathy (STR; a composite measure). Key social-demographic (age, gender, IHS area), diabetes-related health (diabetes therapy, duration of diabetes, A1c), and imaging technology variables were examined. The analysis calculated frequencies and percentages of severity levels of disease. Results: Prevalence of any NPDR, PDR, DME, and STR among AI/AN patients undergoing DR teleophthalmology surveillance by IHS-JVN was 17.7%, 2.3%, 2.3%, and 4.2%, respectively. Prevalence was lowest in Alaska and highest among patients with A1c >/ = 8%, duration of diabetes > 10 years, or using insulin. Conclusions: Prevalence of DR in this cohort was approximately half that in previous reports for AI/AN, and prevalence of DME was less than that reported in non-AI/AN populations. A similar reduction in diabetes related end-stage renal disease in the same population and time period has been reported by other researchers. Since these two diabetic complications share a common microvasculopathic mechanism, this coincident change in prevalence may also share a common basis, possibly related to improved diabetes management. [ABSTRACT FROM AUTHOR]

Background: Although late-onset circulatory collapse (LCC) is widely recognized in Japan, its etiology and the reason for center variation in its incidence remain unclear. This study’s objectives were to identify the perinatal and neonatal factors related to LCC and to estimate the factors related to the center variation in the incidence of LCC. Methods: Extremely preterm infants born between 2008 and 2012 who were registered in the database of the Neonatal Research Network, Japan were retrospectively analyzed. LCC was defined as a clinical diagnosis of LCC and the administration of steroids. We first identified the factors that were significantly related to LCC. We then examined the cause of the center variation in the incidence of LCC, using the standardized incidence ratios (SIRs) of LCC and individual factors. Results: The factors significantly associated with LCC included low gestational age (odds ratio [OR]: 1.13), small for date (OR: 1.43), male sex (OR: 1.26), antenatal steroid use (OR: 1.19), respiratory distress syndrome (OR: 1.25), chronic lung disease at 36 weeks (OR: 1.16), periventricular leukomalacia (PVL) (OR: 2.57), necrotizing enterocolitis (OR: 0.59), retinopathy of prematurity (ROP) (OR: 1.73), high-frequency oscillating ventilation (HFOV) use (OR: 1.31), parenteral nutrition (OR: 1.38), and red blood cell (RBC) transfusion (OR: 1.94). The SIR of LCC ranged from 0.05 to 2.94, and was positively correlated with SIRs of PVL, ROP, HFOV use and RBC transfusion. Conclusion: PVL, ROP, HFOV use and RBC transfusion were found to be correlated with the center variation in the incidence of LCC. [ABSTRACT FROM AUTHOR]

Background: Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR). Methods: In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836) adults (mean age 64.4 ± 9.0 years, 50.4% female) with diabetes from the second visit of two independent population-based cohort studies (2011–15) in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h), normal (6≤ h <8), and long (≥8 h). Questionnaires were administered to detect risk of obstructive sleep apnea (OSA), excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision-threatening DR (VTDR) were analysed using logistic regression models adjusted for potential confounders. Results: Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 ± 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval) of 1.73 (1.03–2.89) and 2.17 (1.28–3.66) respectively. Long sleep duration (2.37 [1.16–4.89]), high risk of OSA (2.24 [1.09–4.75]), and excessive daytime sleepiness (3.27 [1.02–10.30]) were separately associated with VTDR. Conclusion: Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR. [ABSTRACT FROM AUTHOR]

Introduction: Epiretinal traction is not responsible only for epiretinal but also intraretinal changes. This study aims to describe structural and vascular intraretinal changes after macular peeling in idiopathic (iERM) vs diabetic ERM (dERM). Methods: We conducted a prospective interventional study on forty-two eyes, 23 with iERMs and 19 with dERMs, undergoing ERM-ILM peeling. We performed SD-OCT preoperatively, 1 and 6 months postoperatively to assess central macular thickness (CMT), intraretinal cysts (IC) and/or continuous ectopic inner foveal layers (CEIFL), superficial and deep capillary free zone (CFZ) area on OCT-A. Glial fibrillary acidic protein (GFAP), as a Müller cells marker, was detected immunohistochemically on ILM specimens, to assess Müller cells iatrogenic damage. Results: The CEIFLs were significantly more common in iERMs (12 (52.2%) in iERMs vs 2 (10.5%) in dERMs, p = 0.004), whereas ICs in dERMs (6 (26.1%) in iERMs vs 17 (89.5%) in dERMs, p<0.001). Median preoperative and postoperative BCVA was 20/50 [20/40-20/66] and 20/33 [20/25-20/40] in iERMs and 20/100 [20/66-20/200] and 20/50 [20/50-20/66] in dERMs, respectively. Median preoperative and postoperative CMT was 423 [370–488] and 364 [329–382] μm in iERM group and 465 [447–503] and 378 [359–433] μm in dERM group, respectively. The BCVA improvement and reduction of CMT thickness were significant in both groups (p<0.001). The presence of CEIFL was associated with lower BCVA in iERMs. Deep CFZ network significantly increased only in dERMs, passing from 0.34 [0.29–0.42] mm2 preoperatively to 0.56 [0.46–0.6] mm2 at 6-month follow-up (p<0.001). The GFAP expression was significantly higher in dERMs (p = 0.001). Conclusion: The intraretinal changes are different in iERMs and dERMs, as increased expression of CEIFLs in iERMs vs ICs in dERMs. The CEIFLs are associated with worse anatomical and functional outcomes in iERMs, whereas GFAP espression in peeled ILMs is higher in dERMs. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggest retinal microvascular abnormalities predict cardiac events. This study examined microvascular features associated with coronary artery abnormalities. This was a single-centre, cross-sectional, observational study of 144 consecutive subjects undergoing coronary angiography for clinical indications. Their angiograms were deidentified and graded for disease (Leaman score, LAD stenosis ≥ 70%, number of vessels stenosed ≥ 70%), and Thrombolysis in Myocardial Infarction (TIMI) blush score. Subjects also underwent retinal photography (KOWA non-mydriatic camera, Japan), and their deidentified retinal images were graded for hypertensive microvascular retinopathy (Wong and Mitchell classification), vessel calibre using a computer-assisted method (IVAN, U Wisconsin), and diabetic retinopathy (modified Airlie House scheme) independently by a trained grader and an ophthalmologist. Retinal abnormalities were compared between subjects with high and low angiography scores using one way ANOVA, Chi squared and logistic regression analysis (StataCorp, Texas). Subjects had a mean age of 61 years (range 32–88), and included 101 males (70%). Seventeen (12%) had Leaman scores > 10.5, 46 (32%) had LAD stenosis, 13 (9%) had ≥ 3 arteries stenosed, and 20 (14%) had TIMI blush scores < 1. Twenty-six subjects (18%) had a retinal hemorrhage, and 115 (74%) a mild or moderate hypertensive retinopathy. Fifty-five (38%) had diabetes, and 24 (17%) a background (n = 20) or proliferative (n = 4) diabetic retinopathy. A retinal hemorrhage (p = 0.046), moderate microvascular retinopathy (p = 0.08) and proliferative diabetic retinopathy (p = 0.04) were all associated with a higher Leaman score. Venular calibre was increased with triple vessel disease (205.7 ± 21.6 μm, and 193.7 ± 22.3 μm in normals, p = 0.03). Diabetic retinopathy correlated with an increased TIMI blush score (p = 0.01). Retinal microvascular imaging warrants further evaluation in identifying the presence, extent and nature of coronary artery disease. [ABSTRACT FROM AUTHOR]

Background: This study aims to explore retinal vessel calibre in individuals at risk of coronary artery disease (CAD), diagnosed with impaired fasting glucose (IFG) or diabetes mellitus (DM), and whether indices of CAD extent and severity modifies these associations with DM. Methods: A cross-sectional study was undertaken of 1680 patients presenting to Westmead Hospital (Sydney, Australia) for evaluation of potential CAD. Baseline digital retinal photographs, cardiovascular risk factor measurements, fasting blood tests and self-reported diabetes by patient questionnaire was recorded. Extent and severity of CAD was assessed using Extent and Gensini scores from angiography findings, respectively. Multivariate analysis including age and hypertension was undertaken to assess the association between retinal vessel calibre and IFG or DM. Results: A total of 748 patients were included; 96 (12.8%) and 189 (25.3%), respectively, had IFG or DM (together termed ‘hyperglycaemia’). No consistent association between hyperglycaemia and retinal arteriolar calibre was apparent. Wider retinal venular calibre (second and third tertile) carried a significantly higher odds of DM in men only (multivariable-adjusted OR 2.447, p = 0.005; and OR 2.76, p = 0.002; respectively). No equivalent association was apparent in women. This association was marginally significant (p = 0.08) in patients with CAD Extent scores below the median (i.e. less diffuse CAD). Retinal vessel calibre was not associated with impaired fasting glucose. Conclusions: This study reports a significant association between retinal venular widening and diabetes mellitus in men. This association was marginally stronger among participants with less diffuse CAD. [ABSTRACT FROM AUTHOR]

Objective: To assess factors associated with diabetic retinopathy (DR) screening uptake following a diagnosis of type 2 diabetes mellitus (type 2 diabetes) in Germany. Materials and methods: A nationally representative prospective sample of individual-level health claims data for 250,000 members from Germany’s largest public insurance provider in 2004–2013 was assessed. In the sample, 26,560 persons with incident type 2 diabetes were identified. Factors associated with subsequent DR screening were assessed using descriptive statistics, Kaplan-Meier estimator, and Cox regression analysis. Results: On average 27.6 visits to an ophthalmologist per 100 person-years in persons with incident type 2 diabetes occurred. Half of all incident cases (Kaplan-Meier estimator) had not seen an ophthalmologist after more than two years (2.25 years) following their diabetes diagnosis. In the multivariate analysis, an older age (from hazard ratio HR(70–74) = 0.93 [95%-CI: 0.89–0.97] to HR(90+) = 0.50 [95%-CI: 0.42–0.60] compared to persons aged 50–69 years) and a higher disability level (i.e. HR(disability level 3) = 0.30 [95%-CI: 0.25–0.36]) were associated with a lower likelihood, while female sex (HR = 1.12 [95%-CI: 1.08–1.15]), six or more comorbidities (HR = 1.26 [95%-CI: 1.15–1.37]), moderate (HR = 1.51 [95%-CI: 1.46–1.56]) or severe type 2 diabetes (HR = 1.53 [95%-CI: 1.45–1.61]) as well as being enrolled in a type 2 diabetes disease management program (HR = 1.78 [95%-CI: 1.69–1.87]) were associated with a higher likelihood of DR screening. Conclusions: A high proportion of newly diagnosed persons with type 2 diabetes did not follow current German recommendations for DR screening, impeding timely detection and management of potential complications. This was more apparent among persons who were men, older or had a disability. The uptake of screening was considerably greater among those enrolled in a diseases management program. These factors need to be considered when planning DR screening services and/or referrals. [ABSTRACT FROM AUTHOR]