COMPARISON OF THE EFFICACY AND SAFETY OF RANIBIZUMAB 0.5 MG VERSUS 1.0 MG WITH PARS PLANA VITRECTOMY FOR THE TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Controlled Trial.

PURPOSE: To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS: This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS: The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION: Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.

Walking pace and microvascular complications among individuals with type 2 diabetes: A cohort study from the UK Biobank.

INTRODUCTION: Walking pace is associated with various health-related outcomes. The aim of this study was to investigate the association between self-reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). METHODS: Self-reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow-up of 12.5 (interquartile range: 11.6-13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable-adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27-1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27-6.60). CONCLUSIONS: Self-reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population-based cohort study.

Modifiable lifestyle, mental health status and diabetic retinopathy in U.S. adults aged 18-64 years with diabetes: a population-based cross-sectional study from NHANES 1999-2018.

BACKGROUND: The relationship between integrated lifestyles, mental status and their impact on overall well-being has attracted considerable attention. This study aimed to evaluate the association between lifestyle factors, depression and diabetic retinopathy (DR) in adults aged 18-64 years. METHODS: A cohort of 3482 participants diagnosed with diabetes was drawn from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999-2018. DR was defined based on self-reported diabetic retinopathy diagnoses by professional physicians, relying on Diabetes Interview Questionnaires. Subgroup analysis was employed to assess lifestyle and psychological factors between participants with DR and those without, both overall and stratified by diabetic duration. Continuous variables were analyzed using the student's t test, while weighted Rao-Scott χ2 test were employed for categorical variables to compare characteristics among the groups. RESULTS: Of the 3482 participants, 767 were diagnosed with diabetic retinopathy, yielding a weighted DR prevalence of 20.8%. Patients with DR exhibited a higher prevalence of heavy drinking, depression, sleep deprivation, and insufficient physical activity compared to those without DR. Furthermore, multivariable logistic regression analysis revealed that sleeping less than 5 h (OR = 3.18, 95%CI: 2.04-4.95, p < 0.001) and depression (OR = 1.35, 95%CI:1.06-1.64, p = 0.025) were associated with a higher risk of DR, while moderate drinking (OR = 0.49, 95%CI: 0.32-0.75, p = 0.001) and greater physical activity (OR = 0.64, 95%CI: 0.35-0.92, p = 0.044) were identified as protective factors. CONCLUSIONS: Adults aged 18-64 years with DR exhibited a higher prevalence of lifestyle-related risk factors and poorer mental health. These findings underscore the need for concerted efforts to promote healthy lifestyles and positive emotional well-being in this population.

A three-step approach to close refractory persistent macular holes: a releasing-closing-tapping approach.

PURPOSE: The aim of this study was to assess the efficacy and safety of a novel releasing-closing-tapping approach in the treatment of persistent macular holes (PMHs) after initial surgery with internal limiting membrane (ILM) peeling. METHODS: We retrospectively analyzed patients with PMHs after initial surgery with ILM peeling who were treated with a novel releasing-closing-tapping approach. After repeated pars plana vitrectomy (PPV), the surgeon effectively released the adhesion between the edges and retinal pigment epithelium (RPE) by gently scraping the retinal neuroepithelium. Then, the hole was converted into a transverse slit, and the edges were gently tapped flat so that they attached to the RPE, and no space was left under the edges. Finally, air tamponade was carried out. The primary outcome measures included MH closure and the change in best-corrected visual acuity (BCVA) from preoperatively to postoperatively. RESULTS: The study included 11 PMH patients with a mean age of 63.82 ± 3.31 years. The mean minimum linear diameter of PMHs was 666.3 ± 208.1 µm, and the mean basal diameter was 1547.2 ± 351.8 µm. MH closure was achieved in 90.9% (10/11) of eyes, with significant improvement of visual acuity from 1.19 ± 0.30 logMAR to 0.65 ± 0.29 logMAR postoperatively. CONCLUSION: The releasing-closing-tapping approach with repeated PPV is a simple, effective, and safe surgical procedure for refractory PMHs after initial surgery with ILM peeling that can significantly improve the visual outcome and achieve a high surgical success rate.

Dihydroartemisinin ameliorates retinal vascular dysfunction in diabetes mellitus via the FASN/Kmal-mTOR/SREBP1 feedback loop.

Microvascular dysfunction is the primary aetiology of visual impairment caused by diabetic retinopathy (DR). Dihydroartemisinin (DHA), the active metabolite of the antimalarials artemisinins, exhibits antiangiogenic properties in numerous diseases. Here, we investigated the function and mechanisms of DHA as a vasculoprotective agent in DR. DHA exerted its protective effect on vascular injuries in diabetic mice and inhibited cell proliferation and tube formation in human retinal microvascular endothelial cells by decreasing the level of fatty acid synthase (FASN), enhancing the malonylation of mechanistic target of rapamycin (mTOR) at lysine 1218 (K1218) and attenuating the activation of mTOR complex 1 (mTORC1). Impressively, a chemosynthetic small interfering RNA against FASN and mutagenesis of K1218 of mTOR showed therapeutic potential in suppressing cell proliferation and tube formation induced by high glucose. Notably, suppression of mTORC1 kinase activity further inhibited FASN by reducing p70S6K phosphorylation to subsequently reduce the expression of sterol regulatory element binding protein 1, which interacted directly with the FASN promoter at nucleotide positions -64 and -55. In conclusion, our study elucidated the promising effects of FASN and malonylation on vascular injuries of DR and indicated the great potential of DHA as a therapeutic approach.

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses.

OBJECTIVE: An elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR). METHODS: This study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. Multivariable logistic and Cox proportional hazard regression analyses were performed, respectively. VTDR was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or clinically significant macular edema. RESULTS: A total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, higher corrected serum calcium (odds ratio: 1.31 per 0.1 mmol/L, 95% confidence interval: 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium were independently associated with VTDR. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range: 7.4-10.9 years). Higher corrected serum calcium (hazard ratio: 1.38 per 0.1 mmol/L, 95% confidence interval: 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher glycated hemoglobin were identified as independent risk factors for VTDR. CONCLUSIONS: A higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.

The Role of the AIMP1 Pathway in Diabetic Retinopathy: AIMP1-Targeted Intervention Study in Diabetic Retinopathy.

INTRODUCTION: We characterized the role of aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) in retinal inflammation and apoptosis regulation, both in vivo and in vitro. In addition, we used clinical specimens to show the relationship between AIMP1 and the development of diabetic retinopathy (DR). OBJECTIVE: To elucidate the role of AIMP1 in DR. METHODS: A diabetic AIMP1-specific knockout (KO) C57 mouse model was used. Human retinal microvascular endothelial cells (HRMECs) were incubated with normal glucose, high glucose (HG), and HG + AIMP1-small interfering RNA (siRNA). The expression of AIMP1 and relative inflammatory and apoptotic cytokines in diabetic mice retina and HRMECs were measured using Western blotting and polymerase chain reaction. The apoptosis of HRMECs was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The levels of AIMP1 in the vitreous humor and serum were determined using ELISA. Possible correlations between the intravitreal level of AIMP1 and blood glucose, glycosylated hemoglobin HbA1c, intravitreal levels of IL-1ß, and caspase-3 were determined. RESULTS: The expression of inflammatory and apoptotic proteins was inhibited in the AIMP1 KO mice and HRMECs incubated with AIMP1-siRNA. The apoptosis of HRMECs was decreased in the AIMP1-siRNA group. The intravitreal level of AIMP1 in DR patients was significantly higher than that in nondiabetic patients (p < 0.01). There was a positive correlation between intravitreal AIMP1 and HbA1c and intravitreal IL-1ß and caspase-3 (p < 0.05). CONCLUSIONS: HG induced increased expression of AIMP1 in HRMECs and retinas from diabetic C57 mice, thereby increasing the expression of inflammatory and apoptotic cytokines, which promoted DR progression. A decrease in AIMP1 expression prevented the development of DR by inhibiting the activation of inflammatory and apoptotic signaling. Therefore, AIMP1 is an effective interfering target for the prevention and treatment of DR.

Time-lapse angiography of the ocular fundus: a new video-angiography.

BACKGROUND: Ocular fundus angiography is an indispensable component of the tests utilized for fundus diseases. Dynamic angiography results can provide additional information; however, many difficulties remain. In this study, we introduce a modified method, time-lapse angiography (TLA), to dynamically present imaging results. METHODS: TLA, combining time-lapse photography and fundus angiography (using Heidelberg retina angiography II, Germany), includes pre-photographing and post- photosynthesis and ultimately produces a video that is approximately 15 s in length. RESULTS: Four typical videos in the article showed the characteristics of TLA, including a short and rapid but continuous and integral presentation, highly valid information, high definition, etc. CONCLUSIONS: TLA is beneficial for the diagnosis of diseases and the assessment of progression and is convenient for peer communication, patient interpretation, and student education. The application of time-lapse photography in ocular fundus angiography is a monumental and innovative attempt.

Inverted internal limiting membrane flap technique for large macular holes: a systematic review and single-arm meta-analysis.

PURPOSE: The aim of this systematic review was to determine the anatomical outcome-macular hole (MH) closure rate-and functional outcome-visual acuity (VA) improvement rate-of the inverted internal limiting membrane (ILM) flap technique for large MH. METHODS: We searched for articles on large MH (> 400 µm) treated with inverted ILM flap technique in databases as of December 1, 2017. And single-arm meta-analysis was performed for the primary outcome of MH closure rate and the secondary outcome of VA improvement rate. In addition, we searched and pooled studies treating large MH with indocyanine green (ICG)-assisted ILM peeling as the reference. R software (version 2.15.2) was used for analysis. RESULTS: This review includes eight studies that used inverted ILM flap technique to treat large MH (> 400 µm). Based on the single-arm meta-analysis performed in R 2.15.2, the pooled MH closure rate and VA improvement rate following inverted ILM flap technique were 95% (95% CI, 88 to 98%) and 75% (95% CI, 62 to 85%), respectively, in fixed-effect models. There was no substantial methodological heterogeneity. In addition, we selected four studies on large MH treated with ICG-assisted ILM peeling as the reference. The fixed-model pooled MH closure rate and VA improvement rate were 87% (95% CI, 79 to 92%) and 57% (95% CI, 46 to 68%), respectively. CONCLUSIONS: Inverted ILM flap technique should be an effective and safe method for treating large MH, with high closure rates and good VA improvement. However, further studies in large randomized controlled trials on minimizing surgical complications and understanding the mechanism of this technique are necessary.

hsa_circ_0087100/hsa-miR-6743-5p affects Th1 cell differentiation by regulating STAT1 in diabetic retinopathy.

Objective: To elucidate the role of the competitive endogenous RNA (ceRNA) network in immune infiltration of diabetic retinopathy (DR). Methods: We obtained differentially expressed (DE) circRNAs, miRNAs and mRNAs from the Gene Expression Omnibus database. Then, we identified immune infiltration by CIBERSORT and single-sample gene set enrichment analysis and discovered co-expression genes by weighted gene co-expression network analysis. Furthermore, STAT1-mediated Th1 differentiation was determined in DR cell models, DR patients and DR mouse models. Results: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 was involved in immune infiltration of Th1 cells. Aberrant expression of the ceRNA network and STAT1-mediated Th1 differentiation was thus verified in vitro and in vivo. Conclusion: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 may affect Th1 cell differentiation in DR.

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.

Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.

TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy.

BACKGROUND: Studies have shown that tet methylcytosine dioxygenase 2 (TET2) is highly expressed in diabetic retinopathy (DR), which reduces the DNA methylation of downstream gene promoters and activates the transcription. Abnormally expressed TET2 and downstream genes in a high-glucose environment are associated with retinal capillary leakage and neovascularization. Here, we investigated the downstream genes of TET2 and its potential association with neovascularization in proliferative diabetic retinopathy (PDR). METHODS: GSE60436, GSE57362, and GSE158333 datasets were analyzed to identify TET2-related hypomethylated and upregulated genes in PDR. Gene expression and promoter methylation of these genes under high glucose treatment were verified. Moreover, TET2 knockdown was used to assess its impact on tube formation and migration in human retinal microvascular endothelial cells (HRMECs), as well as its influence on downstream genes. RESULTS: Our analysis identified three key genes (PARVB, PTPRE, ECM1) that were closely associated with TET2 regulation. High glucose-treated HRMECs exhibited increased expression of TET2 and ECM1 while decreasing the promoter methylation level of ECM1. Subsequently, TET2 knockdown led to decreased migration ability and tube formation function of HRMECs. We further found a decreased expression of PARVB, PTPRE, and ECM1, accompanied by an increase in the promoter methylation of ECM1. CONCLUSIONS: Our findings indicate the involvement of dysregulated TET2 expression in neovascularization by regulating the promoter methylation and transcription of downstream genes (notably ECM1), eventually leading to PDR. The TET2-induced hypomethylation of downstream gene promoters represents a potential therapeutic target and offers a novel perspective on the mechanism underlying neovascularization in PDR.

Influence of high altitude on choroid thickness, retinal thickness, and myopia: A cross-sectional study comparing adolescents in Shanghai and Tibet.

PURPOSE: This study aimed to explore the influence of high altitude on myopia, macular choroidal thickness (mCT), and macular retinal thickness (mRT) in adolescents. METHODS: Two schools, one in Shanghai (at sea level) and one in Shigatse, Tibet (more than 4000 m above sea level), were selected. Refractive error was measured by an autorefractor instrument and subjective refraction, and mCT and mRT were measured at three concentric circles by optical coherence tomography. Student's t -test, Chi-square test, and multiple linear regression analyses were used to analyze the data. RESULTS: A total of 1114 participants (657 and 457 in Shanghai and Tibet, respectively) were enrolled in this cross-sectional study. The average age of the participants was 18.81 ± 1.10 years, and 44.34% were males. The spherical equivalent (SE) of adolescents in Shanghai was significantly lower than that of adolescents in Tibet (-4.14 ± 2.37 D and -2.12 ± 1.87 D, P < 0.01). The prevalence of myopia and high myopia among adolescents in Shanghai (94.52%, 19.48%) was significantly higher than those among adolescents in Tibet (44.74%, 2.41%) ( P < 0.01). The mCT of Tibetan adolescents was significantly thicker than that of Shanghai adolescents (295.80 ± 62.46 µm and 218.71 ± 61.42 µm, P < 0.01), especially the central mCT. The mRT of Tibetan adolescents was also thicker than that of Shanghai adolescents (301.42 ± 23.26 µm and 281.04 ± 12.24 µm, P < 0.01). CONCLUSIONS: Compared with Shanghai adolescents, the choroid of Tibet adolescents is thicker, and the myopia prevalence is lower. It is speculated that increased altitude is associated with the thickening of mCT and a low myopia prevalence.

Imaging-based body fat distribution and diabetic retinopathy in general US population with diabetes: an NHANES analysis (2003-2006 and 2011-2018).

BACKGROUND: Limited studies have investigated the correlation between fat distribution and the risk of diabetic retinopathy (DR) in the general population with diabetes. The relationship between obesity and DR remains inconclusive, possibly due to using simple anthropometric measures to define obesity. This study investigates the relationships between the android-to-gynoid fat ratio (A/G ratio, measured using dual-energy X-ray absorptiometry) and DR within the US population with diabetes. METHODS: The study used a population-based, cross-sectional approach based on the 2003-2006 and 2011-2018 data of the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analyses were performed on participants with diabetes to evaluate the contribution of body mass index (BMI), waist-to-height ratio (WHtR), and A/G ratio to the prevalence of DR. RESULTS: The prevalence of DR was 22.2, 21.2, and 17.6% among participants with A/G ratios <1.0, 1.0-1.2, and ≥1.2, respectively. After adjusting sex, age, ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level, a higher A/G ratio (≥1.2) was independently associated with decreased odds of DR (odds ratio [OR], 0.565; 95% CI: 0.372-0.858) compared with the A/G ratio of 1.0-1.2. Associations between a higher A/G ratio and DR remained statistically significant after adjusting for BMI (OR, 0.567; 95% CI: 0.373-0.861) and WHtR (OR, 0.586; 95% CI: 0.379-0.907). Moreover, these associations remained statistically significant in analyses using the ethnic-specific tertiles for the A/G ratio. In sex-stratified models, these correlations remained in males. There was a significant inverse association between the A/G ratio and diabetes duration in males, which persisted after multivariable adjustments (p < 0.05). CONCLUSIONS: A novel finding indicates that a higher A/G ratio is associated with a reduced likelihood of DR in males with diabetes. The results from NHANES underscore the importance of considering imaging-based fat distribution as a critical indicator in clinical practice.

Application of artificial intelligence system for screening multiple fundus diseases in Chinese primary healthcare settings: a real-world, multicentre and cross-sectional study of 4795 cases.

BACKGROUND/AIMS: This study evaluates the performance of the Airdoc retinal artificial intelligence system (ARAS) for detecting multiple fundus diseases in real-world scenarios in primary healthcare settings and investigates the fundus disease spectrum based on ARAS. METHODS: This real-world, multicentre, cross-sectional study was conducted in Shanghai and Xinjiang, China. Six primary healthcare settings were included in this study. Colour fundus photographs were taken and graded by ARAS and retinal specialists. The performance of ARAS is described by its accuracy, sensitivity, specificity and positive and negative predictive values. The spectrum of fundus diseases in primary healthcare settings has also been investigated. RESULTS: A total of 4795 participants were included. The median age was 57.0 (IQR 39.0-66.0) years, and 3175 (66.2%) participants were female. The accuracy, specificity and negative predictive value of ARAS for detecting normal fundus and 14 retinal abnormalities were high, whereas the sensitivity and positive predictive value varied in detecting different abnormalities. The proportion of retinal drusen, pathological myopia and glaucomatous optic neuropathy was significantly higher in Shanghai than in Xinjiang. Moreover, the percentages of referable diabetic retinopathy, retinal vein occlusion and macular oedema in middle-aged and elderly people in Xinjiang were significantly higher than in Shanghai. CONCLUSION: This study demonstrated the dependability of ARAS for detecting multiple retinal diseases in primary healthcare settings. Implementing the AI-assisted fundus disease screening system in primary healthcare settings might be beneficial in reducing regional disparities in medical resources. However, the ARAS algorithm must be improved to achieve better performance. TRIAL REGISTRATION NUMBER: NCT04592068.

Exploration of the Potential Mechanisms of Lingqihuangban Granule for Treating Diabetic Retinopathy Based on Network Pharmacology.

BACKGROUND: The Lingqihuangban Granule (LQHBG), a remarkable Chinese herbal compound, has been used for decades to treat diabetic retinopathy (DR) in the Department of Ophthalmology, Shanghai General Hospital (National Clinical Research Center for Eye Diseases) with obvious effects. Through the method of network pharmacology, the present study constructed bioactive component-relative targets and protein-protein interaction network of the LQHBG and implemented gene function analysis and pathway enrichment of targets, discussing the mechanisms of traditional Chinese medicine LQHBG in treating DR. MATERIALS AND METHODS: The bioactive ingredients of LQHBG were screened and obtained using TCMSP and ETCM databases, while the potential targets of bioactive ingredients were predicted by SwissTargetPrediction and ETCM databases. Compared with the disease target databases of TTD, Drugbank, OMIM and DisGeNET, the therapeutic targets of LQHBG for DR were extracted. Based on the DAVID platform, GO annotation and KEGG pathway analyses of key targets were explored, combined with the screening of core pathways on the Omicshare database and pathway annotation on the Reactome database. RESULTS: A total of 357 bioactive components were screened from LQHBG, involving 86 possible targets of LQHBG treating DR. In the PPI network, INS and ALB were identified as key genes. The effective targets were enriched in multiple signaling pathways, such as PI3K/Akt and MAPK pathways. CONCLUSION: This study revealed the possible targets and pathways of LQHBG treating DR, reflecting the characteristics of multicomponent, multitarget and multipathway treatment of a Chinese herbal compound, and provided new ideas for further discussion.

Different associations of anthropometric indices with diabetic retinopathy and diabetic kidney disease in chinese patients with type 2 diabetes mellitus.

AIMS: To investigate the associations of anthropometric indices, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist circumference (WC) and hip circumference (HC), with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This cross-sectional study evaluated 5226 Chinese participants with T2DM at three hospitals between 2005 and 2016. Logistic regression models and restricted cubic spline analysis were used to assess the associations of anthropometric indices with DR and DKD. RESULTS: A BMI of around 25 kg/m2 was related to a low risk of DR (OR based on the third fifth: 0.752, 95%CI: 0.615-0.920). Besides, HC had an inverse association with DR in men independently of BMI (OR based on the highest fifth: 0.495, 95%CI: 0.350-0.697). In the restricted cubic spline models, BMI, WHtR, WC, and HC showed J-shaped associations with DKD, while WHR showed an S-shaped association with DKD. Compared to the lowest fifth, the odds ratios (OR) based on the highest fifth of BMI, WHR, WHtR, WC and HC for DKD were 1.927 (1.572-2.366), 1.566 (1.277-1.923), 1.910 (1.554-2.351), 1.624 (1.312-2.012) and 1.585 (1.300-1.937) respectively in multivariable models. CONCLUSIONS: A median BMI and a large hip might be related to a low risk of DR, while lower levels of all the anthropometric indices were associated with a lower risk of DKD. Our findings suggested maintain a median BMI, a low WHR, a low WHtR and a large hip for prevention of DR and DKD.

FTO fuels diabetes-induced vascular endothelial dysfunction associated with inflammation by erasing m6A methylation of TNIP1.

Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl/fl diabetic mice, EC-specific Fto-deficient (EC FtoΔ/Δ) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnip1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-κB and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnip1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-κB network provides potential targets to treat diabetic vascular complications.

Prevalence and predictors of developing vision-threatening diabetic retinopathy within the first three years of type 2 diabetes.

Purpose: To investigate the prevalence of diabetic retinopathy (DR) and vision-threatening DR (VTDR) in patients with type 2 diabetes mellitus (T2DM) stratified by the duration of diabetes and to identify the clinical variations and risk factors for VTDR occurring at different stages of T2DM. Methods: This was a retrospective comparative study. Patients were divided into short- (≤3 years), intermediate- (3-7 years), and long-duration (>7 years) groups. All patients were followed-up for DR and VTDR development. Risk factors were explored using logistic regression analysis. Results: A total of,2961 patients were included; among them, 1,036 (35.0%) patients developed DR, and 293 (9.9%) had VTDR. The frequency of VTDR in patients who developed DR in the short-duration group was significantly higher than that in the intermediate-duration group (25.7% vs. 15.0%; p = 0.019), but comparable with that of the long-duration group (25.7% vs. 31.8%; p = 0.138). Patients who developed VTDR within the first 3 years of T2DM were more likely to have a family history of diabetes (p = 0.024), had higher glycated hemoglobin (p = 0.025), were males (p = 0.042), and were notably older at the onset of diabetes (p <0.001) but younger when diagnosed with DR (p <0.001). Moreover, higher glycated hemoglobin (OR = 1.14; 95% CI: 1.00-1.29; p = 0.043) and diabetic nephropathy (DN) (OR = 2.31; 95% CI: 1.08-4.91; p = 0.030) were independent risk factors for developing VTDR during the first 3 years of T2DM. Conclusion: The risk of DR is not high in persons with ≤3 years' duration of T2DM, however, if afflicted, the risk of VTDR should never be neglected. More frequent retinal screening is warranted in patients with newly diagnosed T2DM.