Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Elucidating the responses of highly time-resolved PM2.5 related elements to extreme emission reductions.

China's unprecedented lockdown to contain the spread of the novel coronavirus disease (COVID-19) in early 2020, provided a tragic natural experiment to investigate the responses of atmospheric pollution to emission reduction at regional scale. Primarily driven by primary emissions, particulate trace elements is vitally important due to their disproportionally adverse impacts on human health and ecosystem. Here 14 trace elements in PM2.5 were selected for continuous measurement hourly in urban representative site of Shanghai, for three different phases: pre-control period (1-23 January 2020), control period (24 January-10 February 2020; overlapped with Chinese Lunar New Year holiday) and post control period (11-26 February 2020) the city's lockdown measures. The results show that all meteorological parameters (including temperature, RH, mixing layer height et al.) were generally consistent among different periods. Throughout the study period, the concentrations of most species displayed a "V-shaped" trend, suggesting significant effects by the restriction measures imposed during the lockdown period. While this is not the case for species like K, Cu and Ba, indicating their unusual origins. As a case study, the geographical origins of Cu were explored. Seven major sources, i.e., Vehicle-related emission (including road dust; indicative of Ca, Fe, Ba, Mn, Zn, Cu; accounting for 30.1%), shipping (Ni; 5.0%), coal combustion (As, Pb; 4.2%), Se and Cr industry (24.9%), nonferrous metal smelting (Au, Hg; 7.5%) and fireworks burning (K, Cu, Ba; 28.3%) were successfully pinpointed based on positive matrix factorization (PMF) analysis. Our source apportionment results also highlight fireworks burning was one of the dominant source of trace elements during the Chinese Lunar New Year holiday. It is worth noting that 56% of the total mass vehicular emissions are affiliated with non-exhaust sources (tire wear, brake wear, and road surface abrasion).

Influence of segmental supply of Cilioretinal artery on morphology of diabetic macular edema.

BACKGROUND: The supply of Cilioretinal artery (CRA) to different layers of the retina influences retinal pathologies such as diabetic retinopathy (DR). Since the supply of CRA is segmental, our aim was to analyze the location of CRA with respect to non - center involving diabetic macular edema (DME) differentiated by various segments and center involving DME based on Early Treatment of Diabetic Retinopathy Study (ETDRS) scale using optical coherence tomography (OCT). METHODS: A retrospective study was conducted in which forty-three patients with various stages of DR and the presence of CRA were identified. Presence and location of CRA was recognized using fundus fluorescein angiography. Classification of DME was based on ETDRS subfields on OCT. RESULTS: Evaluation of 26 men and 17 women with varying degrees of severity involving DR revealed the presence of unilateral CRA in 40 subjects and bilateral CRA in 3 subjects. When CRA supplied the central area, maximum retinal thickness was noted at the temporal quadrant (271.67 ± 164.02 µm) along with non - center involving DME (194.87 ± 121.06 µm); when CRA supplied the lower area, maximum retinal thickness was noted at the superior quadrant (293.64 ± 159.36 µm) along with center involving DME (395 ± 285.75 µm) and when it supplied the upper area, maximum retinal thickness was noted at the nasal quadrant (293.49 ± 176.18 µm) along with center involving DME (292 ± 192.79 µm). CONCLUSION: The presence of CRA seems to influence the morphology of the retina amongst patients diagnosed with DR by altering the segments involved in DME based on its supply location. However, further studies with a larger sample size are warranted to strenghten this association.

Need for Vitreous Surgeries in Proliferative Diabetic Retinopathy in 10-Year Follow-Up: India Retinal Disease Study Group Report No. 2.

INTRODUCTION: To report the 10-year rate of vitrectomies and the associated factors in people with proliferative diabetic retinopathy (PDR) from a multicentric cohort of people with diabetes mellitus. METHODS: Ten centres in India with established vitreoretinal (VR) services for over 10 years were invited to provide long-term data on PDR. People with Type 1 or 2 diabetes with a clinical diagnosis of active PDR in 1 or both eyes were included. Baseline data collected included age, sex, duration of diabetes, source of referral and best-corrected visual acuity, and diabetic retinopathy status in both eyes. Available follow-up data included the numbers of panretinal photocoagulation (PRP) sessions, cataract surgery, treatment of diabetic macular oedema, use of anti-vascular endothelial growth factor (VEGF) therapy, vitrectomy with or without retinal surgeries over 10 years. RESULTS: Over 10 years, 89% needed supplemental PRP after initial complete PRP. One-third required retinal surgery, 16% needed intravitreal injection. Men (74.5%) had significant higher risk for vitreous (VR) surgery. Of the group with low-risk PDR, 56.8% did not require VR surgery, p < 0.001. Of the patients who underwent cataract surgery and had intravitreal anti-VEGF injections, 78.5 and 28.2% needed subsequent vitreous (VR) surgery, p = 0.006 and <0.0001, respectively. Independent predictors of need for vitreoretinal surgery included those who underwent cataract surgery and those with poor baseline visual acuity (logMAR). Eyes at lower risk for VR surgery included the eyes previously treated with PRP and low-risk PDR at baseline. CONCLUSION: Despite initial "complete" PRP, one-third of our study cohort needed vitrectomies over 10 years, highlighting that these patients require regular follow-up for a long period of time.

Reduction of surface radiative forcing observed from remote sensing data during global COVID-19 lockdown.

The calamity of the COVID-19 pandemic during the early half of 2020 not only caused a huge physical and economic loss but altered the social behavior of the whole world. The social and economic stagnation imposed in many countries and served as a major cause of perturbation in atmospheric composition. This paper utilized the relation between atmospheric composition and surface radiation and analyzed the impact of global COVID-19 lockdown on land surface solar and thermal radiation. Top of atmosphere (TOA) and surface radiation are obtained from the Clouds and Earth's Radiant Energy System (CERES) and European Reanalysis product (ERA5) reanalysis product. Aerosol Optical Depth (AOD) is obtained from Moderate Resolution Imaging Spectroradiometer (MODIS) while Nitrogen dioxide (NO2), and sulfur dioxide (SO2) are obtained from Ozone Monitoring Instrument (OMI). Observations of all mentioned parameters are studied for the global lockdown period of 2020 (from January to July) and compared with the corresponding months of the previous four years (2016-19) observations. Regarding surface radiation, April 2020 is the most affected month during the pandemic in which 0.2% increased net solar radiation (NSR), while 3.45% and 4.8% decreased net thermal radiation (NTR) and net radiation (NR) respectively was observed. Average radiative forcing during March-May 2020 was observed as 1.09 Wm-2, -2.19 Wm-2 and -1.09 Wm-2 for NSR, NTR and NR, respectively. AOD was reduced by 0.2% in May 2020 while NO2 and SO2 were reduced by 5.4% and 8.8%, respectively, in April 2020. It was observed that NO2 kept on reducing since January 2020 while SO2 kept on reducing since February 2020 which were the pre-lockdown months. These results suggest that a more sophisticated analysis is needed to explain the atmosphere-radiation relation.

Age of Onset of Diabetes and Its Comparison with Prevalence and Risk Factors for Diabetic Retinopathy in a Rural Population of India.

AIM: To compare the age of onset of diabetes with the prevalence and risk factors of diabetic retinopathy (DR) in a rural population of India. METHODS: This is a population-based study for which 1,190 people with diabetes were recruited from rural areas of the districts of Kanchipuram and Thiruvallur, Tamil Nadu, India. The fundi of all patients were photographed using a 45°, four-field stereoscopic digital fundus camera. The diagnosis of DR was based on the Klein classification of the Early Treatment Diabetic Retinopathy Study scale. RESULTS: The prevalence of DR was 11.5% in individuals with known onset of diabetes (aged ≤40 years) compared to 10.0% in those with late onset. The risk factors for any DR in both groups included longer known duration of diabetes, use of insulin, and the presence of high systolic blood pressure and hypertension. In the group with known onset of diabetes at ≤40 years, older age (p < 0.0001) and male gender (p = 0.018) were the significant factors for DR. In the group with age of onset of diabetes at > 40 years, high diastolic pressure (p = 0.001), higher HbA1c (p < 0.0001), high microalbuminuria (p < 0.0001), and high macroalbuminuria (p < 0.008) were the significant risk factors for DR. CONCLUSION: Control of risk factors in people with younger age of onset of diabetes may reduce both the prevalence and impact of retinopathy in rural populations.

A randomized control trial of primary care-based management of type 2 diabetes by a pharmacist in Pakistan.

BACKGROUND: The role of a pharmacist in primary health care settings of Pakistan is still obscure. Thus, we aimed to demonstrate the pharmacist-led improvements in glycemic, blood pressure and lipid controls in type 2 diabetes mellitus (T2DM) patients of Lahore, Pakistan. METHODS: The first open label, randomized control trial conducted at a primary health care facility of Lahore, Pakistan by enrolling 244 uncontrolled type 2 diabetes (hemoglobin A1 c, (HbA1c); 10.85 ± 1.74) patients. The pharmacological intervention included identification of drug related problems, drug interactions, change in dose, frequency and therapy switches in collaboration with physician, while non-pharmacological intervention consisted of diet, lifestyle and behavior counseling. Outcome measures were glycemic (HbA1c), blood pressure and lipid controls. RESULTS: In intra-group comparison, compared to control arm (C, n = 52), subjects in the intervention arm (I, n = 83) demonstrated significant differences in process outcome measures; baseline vs final, such as HbA1c (C; 10.3 ± 1.3 vs 9.7 ± 1.3, p <  0.001, I; 10.9 ± 1.7 vs 7.7 ± 0.9, p <  0.0001), systolic blood pressure (SBP) (C; 129.9 ± 13.9 vs 136 ± 7.1, p = 0.0001, I; 145 ± 20.4 vs 123.9 ± 9.9 mmHg, p <  0.0001), diastolic blood pressure (DBP) (C; + 4, p = 0.03, I; - 7 mmHg, p <  0.0001), cholesterol (C; 235.8 ± 57.7 vs 220.9 ± 53.2, p = 0.15, I; 224 ± 55.2 vs 153 ± 25.9 mg/dL, p < 0.0001), triglycerides (C; 213.2 ± 86.6 vs 172.4 ± 48.7, p = 0.001, I; 273 ± 119.4 vs 143 ± 31.6 mg/dL, p < 0.0001) and estimated glomerular filtration rate (eGFR) (C; 77.5 ± 18.6 vs 76 ± 14.2, p = 0.5, I; 69.4 ± 21.3 vs 93.8 ± 15.2 ml/min/1.73m2, p < 0.0001). Likewise, inter-group improvements were more significant in the subjects of intervention group at final follow up in comparison to control for various process outcome measures; HbA1c (p < 0.001), SBP (p < 0.0001), DBP (p = 0.02), cholesterol (p < 0.0001), triglycerides (p < 0.0001), SCr (p < 0.001), eGFR (p < 0.001). Moreover, both male and female subjects exhibited similar responses towards intervention with similar improvements in outcome measures. CONCLUSION: These data suggested that pharmacist intervention in collaboration with physician in primary health care settings may result in significant improvements in glycemic, blood pressure and lipid controls in Pakistani population. TRIAL REGISTRATION: The trial was registered retrospectively with International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry on July 26, 2017 under nutritional, metabolic, endocrine category with assigned registration # ISRCTN22657497 and can be assessed at https://doi.org/10.1186/ISRCTN22657497.

Evidence Favoring a Positive Feedback Loop for Physiologic Auto Upregulation of hnRNP-E1 during Prolonged Folate Deficiency in Human Placental Cells.

Background: Previously, we determined that heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) functions as an intracellular physiologic sensor of folate deficiency. In this model, l-homocysteine, which accumulates intracellularly in proportion to the extent of folate deficiency, covalently binds to and thereby activates homocysteinylated hnRNP-E1 to interact with folate receptor-α mRNA; this high-affinity interaction triggers the translational upregulation of cell surface folate receptors, which enables cells to optimize folate uptake from the external milieu. However, integral to this model is the need for ongoing generation of hnRNP-E1 to replenish homocysteinylated hnRNP-E1 that is degraded.Objective: We searched for an interrelated physiologic mechanism that could also maintain the steady-state concentration of hnRNP-E1 during prolonged folate deficiency.Methods: A novel RNA-protein interaction was functionally characterized by using molecular and biochemical approaches in vitro and in vivo.Results: l-homocysteine triggered a dose-dependent high-affinity interaction between hnRNP-E1 and a 25-nucleotide cis element within the 5'-untranslated region of hnRNP-E1 mRNA; this led to a proportionate increase in these RNA-protein complexes, and translation of hnRNP-E1 both in vitro and within placental cells. Targeted perturbation of this RNA-protein interaction either by specific 25-nucleotide antisense oligonucleotides or mutation within this cis element or by small interfering RNA to hnRNP-E1 mRNA significantly reduced cellular biosynthesis of hnRNP-E1. Conversely, transfection of hnRNP-E1 mutant proteins that mimicked homocysteinylated hnRNP-E1 stimulated both cellular hnRNP-E1 and folate receptor biosynthesis. In addition, ferrous sulfate heptahydrate [iron(II)], which also binds hnRNP-E1, significantly perturbed this l-homocysteine-triggered RNA-protein interaction in a dose-dependent manner. Finally, folate deficiency induced dual upregulation of hnRNP-E1 and folate receptors in cultured human cells and tumor xenografts, and more selectively in various fetal tissues of folate-deficient dams.Conclusions: This novel positive feedback loop amplifies hnRNP-E1 during prolonged folate deficiency and thereby maximizes upregulation of folate receptors in order to restore folate homeostasis toward normalcy in placental cells. It will also functionally impact several other mRNAs of the nutrition-sensitive, folate-responsive posttranscriptional RNA operon that is orchestrated by homocysteinylated hnRNP-E1.

Characteristics and optical properties of atmospheric aerosols based on long-term AERONET investigations in an urban environment of Pakistan.

Radiative balance, local climate, and human health are all significantly influenced by aerosol. Recent severe air pollution over Lahore, a city in Pakistan calls for more thorough research to determine the negative impacts brought on by too many aerosols. To study regional aerosol characteristics and their differences from various aspects, in-depth and long-term (2007-2020) investigations of the columnar aerosol properties over the urban environment of Lahore were carried out by using AERONET data. The Aerosol Optical Depth (AOD400) and Angstrom Exponent (AE400-870) vary from low values of 0.10 to a maximum value of 4.51 and from 0.03 to 1.81, respectively. The huge differences in the amount of AOD440 as well as AE440-870 show the large fluctuation of aerosol classes because of various sources of their emission. During the autumn and winter seasons, the decreasing trend of the optical parameters of aerosols like Single Scattering Albedo (SSA) and Asymmetry Parameter (ASY) with increasing wavelength from 675 to 1020 nm indicates the dominance of light-absorbing aerosols (biomass burning (BB) and industrial/urban (UI). Due to the long-distance dust movement during spring, summer, and autumn, coarse mode particles predominated in Lahore during the study period. Dust type (DD) aerosols are found to be the dominant one during spring (46.92%), summer (54.31%), and autumn (57.46%) while urban industry (BB/UI) was dominant during the winter season (53.21%). During each season, the clean continental (CC) aerosols are found to be in negligible amounts, indicating terrible air quality in Lahore City. The present research work fills up the study gap in the optical properties of aerosols in Lahore and will help us understand more fully how local aerosol fluctuation affects regional climate change over the urban environment of Lahore.

Influence of physiologic folate deficiency on human papillomavirus type 16 (HPV16)-harboring human keratinocytes in vitro and in vivo.

Although HPV16 transforms infected epithelial tissues to cancer in the presence of several co-factors, there is insufficient molecular evidence that poor nutrition has any such role. Because physiological folate deficiency led to the intracellular homocysteinylation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) and activated a nutrition-sensitive (homocysteine-responsive) posttranscriptional RNA operon that included interaction with HPV16 L2 mRNA, we investigated the functional consequences of folate deficiency on HPV16 in immortalized HPV16-harboring human (BC-1-Ep/SL) keratinocytes and HPV16-organotypic rafts. Although homocysteinylated hnRNP-E1 interacted with HPV16 L2 mRNA cis-element, it also specifically bound another HPV16 57-nucleotide poly(U)-rich cis-element in the early polyadenylation element (upstream of L2L1 genes) with greater affinity. Together, these interactions led to a profound reduction of both L1 and L2 mRNA and proteins without effects on HPV16 E6 and E7 in vitro, and in cultured keratinocyte monolayers and HPV16-low folate-organotypic rafts developed in physiological low folate medium. In addition, HPV16-low folate-organotypic rafts contained fewer HPV16 viral particles, a similar HPV16 DNA viral load, and a much greater extent of integration of HPV16 DNA into genomic DNA when compared with HPV16-high folate-organotypic rafts. Subcutaneous implantation of 18-day old HPV16-low folate-organotypic rafts into folate-replete immunodeficient mice transformed this benign keratinocyte-derived raft tissue into an aggressive HPV16-induced cancer within 12 weeks. Collectively, these studies establish a likely molecular linkage between poor folate nutrition and HPV16 and predict that nutritional folate and/or vitamin-B(12) deficiency, which are both common worldwide, will alter the natural history of HPV16 infections and also warrant serious consideration as reversible co-factors in oncogenic transformation of HPV16-infected tissues to cancer.

Incrimination of heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) as a candidate sensor of physiological folate deficiency.

The mechanism underlying the sensing of varying degrees of physiological folate deficiency, prior to adaptive optimization of cellular folate uptake through the translational up-regulation of folate receptors (FR) is unclear. Because homocysteine, which accumulates intracellularly during folate deficiency, stimulated interactions between heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) and an 18-base FR-α mRNA cis-element that led to increased FR biosynthesis and net up-regulation of FR at cell surfaces, hnRNP-E1 was a plausible candidate sensor of folate deficiency. Accordingly, using purified components, we evaluated the physiological basis whereby L-homocysteine triggered these RNA-protein interactions to stimulate FR biosynthesis. L-homocysteine induced a concentration-dependent increase in RNA-protein binding affinity throughout the range of physiological folate deficiency, which correlated with a proportionate increase in translation of FR in vitro and in cultured human cells. Targeted reduction of newly synthesized hnRNP-E1 proteins by siRNA to hnRNP-E1 mRNA reduced both constitutive and L-homocysteine-induced rates of FR biosynthesis. Furthermore, L-homocysteine covalently bound hnRNP-E1 via multiple protein-cysteine-S-S-homocysteine mixed disulfide bonds within K-homology domains known to interact with mRNA. These data suggest that a concentration-dependent, sequential disruption of critical cysteine-S-S-cysteine bonds by covalently bound L-homocysteine progressively unmasks an underlying RNA-binding pocket in hnRNP-E1 to optimize interaction with FR-α mRNA cis-element preparatory to FR up-regulation. Collectively, such data incriminate hnRNP-E1 as a physiologically relevant, sensitive, cellular sensor of folate deficiency. Because diverse mammalian and viral mRNAs also interact with this RNA-binding domain with functional consequences to their protein expression, homocysteinylated hnRNP-E1 also appears well positioned to orchestrate a novel, nutrition-sensitive (homocysteine-responsive), posttranscriptional RNA operon in folate-deficient cells.

The Longitudinal Assessment of Vascular Parameters of the Retina and Their Correlations with Systemic Characteristics in Type 2 Diabetes-A Pilot Study.

The aim of the study was to assess various retinal vessel parameters of diabetes mellitus (DM) patients and their correlations with systemic factors in type 2 DM. A retrospective exploratory study in which 21 pairs of baseline and follow-up images of patients affected by DM were randomly chosen from the Sankara Nethralaya−Diabetic Retinopathy Study (SN DREAMS) I and II datasets. Patients' fundus was photographed, and the diagnosis was made based on Klein classification. Vessel thickness parameters were generated using a web-based retinal vascular analysis platform called VASP. The thickness changes between the baseline and follow-up images were computed and normalized with the actual thicknesses of baseline images. The majority of parameters showed 10~20% changes over time. Vessel width in zone C for the second vein was significantly reduced from baseline to follow-up, which showed positive correlations with systolic blood pressure and serum high-density lipoproteins. Fractal dimension for all vessels in zones B and C and fractal dimension for vein in zones A, B and C showed a minimal increase from baseline to follow-up, which had a linear relationship with diastolic pressure, mean arterial pressure, serum triglycerides (p < 0.05). Lacunarity for all vessels and veins in zones A, B and C showed a minimal decrease from baseline to follow-up which had a negative correlation with pulse pressure and positive correlation with serum triglycerides (p < 0.05). The vessel widths for the first and second arteries significantly increased from baseline to follow-up and had an association with high-density lipoproteins, glycated haemoglobin A1C, serum low-density lipoproteins and total serum cholesterol. The central reflex intensity ratio for the second artery was significantly decreased from baseline to follow-up, and positive correlations were noted with serum triglyceride, serum low-density lipoproteins and total serum cholesterol. The coefficients for branches in zones B and C artery and the junctional exponent deviation for the artery in zone A decreased from baseline to follow-up showed positive correlations with serum triglycerides, serum low-density lipoproteins and total serum cholesterol. Identifying early microvascular changes in diabetic patients will allow for earlier intervention, improve visual outcomes and prevent vision loss.

Revised Glycemic Index for Diagnosing and Monitoring of Diabetes Mellitus in South Indian Population.

AIM: To find the optimal threshold of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) for diagnosis of diabetes mellitus (DM) and to evaluate the association with diabetic retinopathy (DR) in the South Indian population. SETTINGS AND DESIGN: A retrospective population-based study. METHODS AND MATERIALS: A total of 909 newly detected type 2 DM patients were selected from our two previously conducted studies, which include an urban and a rural population of South India. All underwent estimation of fasting, postprandial plasma glucose (PPG), and other biochemical tests. A comprehensive and detailed ophthalmic examination was carried out. The fundi of patients were photographed using 45°, four-field stereoscopic photography. Based on receiver operating characteristic (ROC) curves, sensitivity and specificity were derived. RESULTS:  The optimal cut-off values determined by maximizing the sensitivity and specificity of FPG and HbA1c using the Youden index were ≥ 6.17 mmol/L and ≥ 6.3%, respectively. By distributing the cut-off points into deciles and comparing them to the WHO criteria, we found that our HbA1c level of 6.60% was more than the WHO threshold (6.5%), with higher sensitivity (81.6%) and lower specificity (48.3%). The FPG level of 6.80 mmol/L was lower to the WHO criteria (7 mmol/L) with increased sensitivity (77.0%) and lower specificity (45.7%). Prevalence of DR by HbA1c levels between 6.5% and 6.9% was 15.3%. The prevalence of DR was more in the FPG category between 6.4 and 6.9 mmol/L and ≥ 7.5 mmol/L. CONCLUSION: Our population-based data indicate that for the South Indian population HbA1c value of ≥63 % and FPG value of ≥6.17 mmol/L may be optimal for diagnosing DM with a high level of accuracy and will be useful for the identification of mild and moderate DR.

Predominant peripheral lesions in patients with diabetic retinopathy and its association with systemic comorbidities.

Purpose: To determine the associations of predominant peripheral lesions (PPLs) with systemic comorbidities in individuals with diabetic retinopathy. Methods: This is a multicenter cross-sectional observational study conducted across three tertiary eye care centers in south India between January 2019 and July 2021. Ultra-widefield fundus images of consecutive patients with varying severity of diabetic retinopathy with data on systemic comorbidities were classified based on the presence or absence of PPL. Systemic comorbidities (hypertension, diabetic kidney disease, coronary artery disease, dyslipidemia, and anemia) were compared between the two groups. Results: A total of 879 participants (70.1% males) were included in the study, of which 443 (50.4%) patients had PPL. The mean age of the study participants was 56 ± 10 years, mean age of onset of diabetes was 41.24 ± 11.6 years, and mean duration of diabetes was 15.39 ± 7.6 years. The number of PPL increased with increasing severity of DR. Of all the systemic comorbidities analyzed, we found that coronary artery disease (CAD) had a significant association with PPL (Odds ratio [OR]-1.69; 95% confidence interval [CI], 1.12-2.55; P = 0.013) after adjusting for diabetic retinopathy severity, duration of diabetes, and age of onset of diabetes. Conclusion: The presence of PPL is a marker for coronary artery disease and early referral to cardiology is warranted.

Younger Age and Albuminuria are Associated with Proliferative Diabetic Retinopathy and Diabetic Macular Edema in the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study.

Purpose: The purpose of the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study is to identify non-genetic and genetic risk factors associated with diabetic retinopathy (DR). This report examines the non-genetic risk factors for DR in South Indian patients.Methods: Participants with South Indian ancestry and type 2 diabetes (T2D) were included from two sources: the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study (SN-DREAMS) and prospective recruitment at Sankara Nethralaya affiliates. Fundus photography and optical coherence tomography (OCT) were obtained on participants. Fundus images were graded for DR severity and OCTs were graded for center-involved diabetic macular edema (ciDME). Multivariate analyses were performed using stepwise logistic regression to assess effects of the demographic and clinical factors on proliferative DR (PDR) and DME.Results: Among the 2941 participants with DR grading, participants with PDR were more likely to be younger [odds ratio (OR)=0.95], men (OR = 1.83), have a longer duration of diabetes (OR = 1.10), have a higher hemoglobin A1c (OR = 1.12), have albuminuria (OR = 5.83), have hypertension (OR = 1.69), have a higher HDL (OR = 1.02) and a lower total cholesterol (OR = 0.99) (all p < 0.05). Among the 483 participants with gradable OCT scans, participants who had ciDME were more likely to be younger (OR = 0.97), men (OR = 2.80), have a longer duration of diabetes (OR = 1.06), have lower triglycerides (OR = 0.99), and have albuminuria (OR = 3.12) (all p < 0.05).Conclusions: Younger age, male sex, longer duration of diabetes, higher HbA1c, and presence of albuminuria were identified as risk factors for PDR and DME in a South Indian population with T2D.

Assessment of variations of air pollutant concentrations during the COVID-19 lockdown and impact on urban air quality in South Asia.

Quantifying the variations of atmospheric aerosols and trace gas concentrations with the impact of lockdown due to the Coronavirus disease of 2019 (COVID-19) pandemic is crucial in understanding urban air quality. For this purpose, we utilized the multi-instrumental approach of satellite remote sensing and reanalysis model data to examine the spatial and temporal patterns of major air pollutants during December 2019-June 2020 in South Asia. The lockdown has to lead to a considerable decrease in aerosol optical thickness (AOT) over South China (-18.92%) and Indo-Gangetic Plain (IGP; -24.29%) compared to its ordinary level for a couple of weeks. Noticeable reductions in tropospheric NO2 are observed over the Pearl River Delta (PRD; -0.3/cm2) followed by Central China (CC) with -0.21/cm2and IGP (-0.085/cm2), and the lowest (-0.0008/cm2) in the Tibetan Plateau (TP) region. The changes observed in PM2.5 and SO2 levels (from -58.56% to - 63.64%) are attributed to the decrease in anthropogenic emissions, vehicular exhaust, and industrial activities. However, the BC concentrations are reduced by approximately halved of its ordinary levels in the IGP (-2.28 µg/m3) followed by YRD (-1.56 µg/m3), CC (-1.5 µg/m3), NCP (-1.29 µg/m3), and PRD (-0.78 µg/m3) regions. The total column O3 predominantly increased from 262.68 to 285.53DU, 323.00 to 343.00DU, and 245.00 to 265.00DU in the YRD, NCP, and IGP areas. This is mainly associated with solar radiation, meteorological factors, and an unprecedented reduction in NOx during the lockdown period.

Association Between Gut Microbial Abundance and Sight-Threatening Diabetic Retinopathy.

Purpose: To study the association between gut microbial abundance and sight-threatening diabetic retinopathy among patients with a history of type 2 diabetes mellitus. Methods: An observational case-control study was performed using a sample population of diabetics referred to a tertiary eye institute. Sample subjects were identified as cases if they were diagnosed with sight-threatening diabetic retinopathy and controls if they were not but had at least a 10-year history of diabetes. Fecal swabs for all patients were collected for enumeration and identification of sequenced gut microbes. Statistical analyses were performed to associate the clinically relevant Bacteroidetes to Firmicutes relative abundance ratio (B/F ratio) with sight-threatening diabetic retinopathy and an optimal cutoff value for the ratio was identified using Youden's J statistics. Results: A sample size of 58 diabetic patients was selected (37 cases, 21 controls). No statistically significant difference in the relative abundance among the predominant phyla between the groups were found. In our univariate analysis, the B/F ratio was elevated in cases compared to controls (cases, 1.45; controls, 0.94; P = 0.049). However, this statistically significant difference was not seen in our multivariate regression model. Optimal cutoff value of 1.05 for the B/F ratio was identified, and significant clustering of cases above this value was noted in beta diversity plotting. Conclusions: No difference in gut microbial abundance for any particular phylum was noted between the control and diseased population. Increased gut microbial B/F ratio can be a potential biomarker for the development of sight-threatening diabetic retinopathy among type 2 diabetic patients.

Choroidal Structural Changes in Sympathetic Ophthalmia on Swept-Source Optical Coherence Tomography.

Purpose: To analyze choroidal angioarchitecture in sympathetic ophthalmia (SO) using swept-source optical coherence tomography (SS-OCT) images.Methods: Case-control study of six patients with SO. Qualitative changes and quantitative parameters, including choroidal thickness (CT) and choroidal vascularity index (CVI), were analyzed.Results: Qualitative findings in the acute phase of SO on SS-OCT included retinal serous detachment with hyperreflective septa, choroidal folds, alterations in angioarchitecture with loss of vascular lacunae, and Dalen-Fuchs nodules. There was significantly higher CT in SO (284.05 ± 24.12 µm) compared to healthy controls (229.57 ± 46.67 µm, p = 0.04) and also increased CVI in SO (62.06 ± 2.07% vs 56.79 ± 3.15%, p = 0.006).Conclusions: CVI was significantly increased in SO, representing a novel noninvasive biomarker of disease activity. SS-OCT provides a useful qualitative and quantitative parameter, which can be potentially explored in the diagnosis and monitoring of patients with SO.

Comparison of Two Ultra-Widefield Cameras With High Image Resolution and Wider View for Identifying Diabetic Retinopathy Lesions.

Purpose: To compare the effectiveness of the Optos P200dTx and Zeiss Clarus 500 fundus cameras in detecting diabetic retinopathy (DR) lesions. Methods: A cross-sectional study was conducted among 243 patients with clinically diagnosed diabetes mellitus who were referred for an eye examination from two tertiary eye care centers in Chennai, India. Patients underwent DR screening based on mydriatic fundal images acquired by both fundal cameras. Fundal images from the two separate devices for each eye were compared based on accurately identified pathological retinal lesions with respect to type and location. Results: When studying lesions of the central retina, they were better identified by the Zeiss Clarus compared with the Optos P200dTx, with six out of eight being statistically significant (P < 0.05). However, lesions of the mid-peripheral retina and peripheral retina were better identified by the Optos P200dTx than the Zeiss Clarus, with three out of eight lesions and five out of eight lesions being statistically significant (P < 0.05), respectively. Based on the color and size of lesions, the Optos P200dTx had a higher chance (59.6%) of missing white lesions than did the Zeiss Clarus (17%) (P < 0.0001). Consequently, small- and medium-sized lesions were missed more by the Optos P200dTx (30.72% and 32.63%, respectively) than the Zeiss Clarus (22.3% and 19.30%, respectively). Conclusions: The capability of detecting or missing a particular DR lesion among diabetics differed between the two cameras based on effective field of view, resolution, and the retinal zone being imaged. Translational Relevance: The choice of which ultra-widefield camera to be used for screening DR can be based on the greater prevalence of central versus peripheral retinal lesions noted in the patient population seen in a clinical practice.

Detection of Diabetic Retinopathy from Ultra-Widefield Scanning Laser Ophthalmoscope Images: A Multicenter Deep Learning Analysis.

PURPOSE: To develop a deep learning (DL) system that can detect referable diabetic retinopathy (RDR) and vision-threatening diabetic retinopathy (VTDR) from images obtained on ultra-widefield scanning laser ophthalmoscope (UWF-SLO). DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 9392 UWF-SLO images of 1903 eyes from 1022 subjects with diabetes from Hong Kong, the United Kingdom, India, and Argentina. METHODS: All images were labeled according to the presence or absence of RDR and the presence or absence of VTDR. Labeling was performed by retina specialists from fundus examination, according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Three convolutional neural networks (ResNet50) were trained with a transfer-learning procedure for assessing gradability and identifying VTDR and RDR. External validation was performed on 4 datasets spanning different geographical regions. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC); area under the precision-recall curve (AUPRC); sensitivity, specificity, and accuracy of the DL system in gradability assessment; and detection of RDR and VTDR. RESULTS: For gradability assessment, the system achieved an AUROC of 0.923 (95% confidence interval [CI], 0.892-0.947), sensitivity of 86.5% (95% CI, 77.6-92.8), and specificity of 82.1% (95% CI, 77.3-86.2) for the primary validation dataset, and >0.82 AUROCs, >79.6% sensitivity, and >70.4% specificity for the geographical external validation datasets. For detecting RDR and VTDR, the AUROCs were 0.981 (95% CI, 0.977-0.984) and 0.966 (95% CI, 0.961-0.971), with sensitivities of 94.9% (95% CI, 92.3-97.9) and 87.2% (95% CI, 81.5-91.6), specificities of 95.1% (95% CI, 90.6-97.9) and 95.8% (95% CI, 93.3-97.6), and positive predictive values (PPVs) of 98.0% (95% CI, 96.1-99.0) and 91.1% (95% CI, 86.3-94.3) for the primary validation dataset, respectively. The AUROCs and accuracies for detecting both RDR and VTDR were >0.9% and >80%, respectively, for the geographical external validation datasets. The AUPRCs were >0.9, and sensitivities, specificities, and PPVs were >80% for the geographical external validation datasets for RDR and VTDR detection. CONCLUSIONS: The excellent performance achieved with this DL system for image quality assessment and detection of RDR and VTDR in UWF-SLO images highlights its potential as an efficient and effective diabetic retinopathy screening tool.