Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract:a randomized clinical trial

●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.

Peripapillary vessel density and retinal nerve fiber layer thickness changes in early diabetes retinopathy

·AIM:To perform a quantitative analysis of the peripapillary vessel density(VD)and retinal nerve fiber layer(RNFL)thickness changes in patients with early stage of diabetic retinopathy(DR).·METHODS:In this case-control study,swept-source optical coherence tomography angiography(SS-OCTA)imaging was used to examine diabetic and age-matched healthy subjects.The optic disc HD 6×6 mm^(2) blood flow imaging scan mode was selected.Automatic software was used to measure the peripapillary VD,capillary vessel density(CVD),and RNLF in an optic nerve head(ONH)filed based on the Garway-Heath map.In addition,the correlation between peripapillary VD,CVD,and RNFL was further investigated.·RESULTS:The cohort consisted of 32 healthy individuals and 72 patients with diabetes(34 eyes with no DR and 38 eyes with mild-moderate NPDR).Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions(P<0.05).Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal(ST)quadrants(P=0.018.P=0.030).In the correlation analysis of each region,the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD(r=0.233,P=0.05;r=0.288.P=0.015).In the TI region,the RNFL thickness was positively correlated with the peripapillary CVD(r=0.237,P=0.047).·CONCLUSION:The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR.The peripapillary VD,CVD and RNFL decrease in early DR,and the RNFL thickness altered in association with the CVD or/and VD in some regions.

Correlation of periodontal inflamed surface area with glycated hemoglobin,interleukin-6 and lipoprotein(a)in type 2 diabetes with retinopathy

BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic complications.An inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the literature.AIM To determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in T2DM subjects with retinopathy.METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR.All subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5%and 27.5%respectively.Severity of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in T2DM with DR group compared to T2DM without DR group.Significant difference was observed in the mean percentage of sites with BOP between T2DM with DR(69%)and T2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,P<0.0001);PISA and Lp(a)(r=0.59,P<0.001);CAL and IL-6(r=0.527,P<0.0001)and CAL and Lp(a)(r=0.631,P<0.001)among study subjects.CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to T2DM without DR.Since a bidirectional link exists between periodontitis and DM,the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Risk evaluation for diabetic retinopathy in Chinese renalbiopsied type 2 diabetes mellitus patients

AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this population.METHODS:A total of 84 renal-biopsied T2DM patients were included.Fundus and imaging examinations were employed for DR diagnosis.Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups.Risk factors on DR development were analyzed with multiple logistic regression.RESULTS:DR prevalence was 50%in total.The incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR group.Systolic blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR group.Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively correlated.CONCLUSION:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

Systemic immune-inflammation index,neutrophilto-lymphocyte ratio,and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy

AIM:To investigate systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and plateletto-lymphocyte ratio(PLR)levels in patients with type 2 diabetes at different stages of diabetic retinopathy(DR).METHODS:This retrospective study included 141 patients with type 2 diabetes mellitus(DM):45 without diabetic retinopathy(NDR),47 with non-proliferative diabetic retinopathy(NPDR),and 49 with proliferative diabetic retinopathy(PDR).Complete blood counts were obtained,and NLR,PLR,and SII were calculated.The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic(ROC)curves.The relationships between DR stages and SII,PLR,and NLP were assessed using multivariate logistic regression.RESULTS:The average NLR,PLR,and SII were higher in the PDR group than in the NPDR group(P=0.011,0.043,0.009,respectively);higher in the NPDR group than in the NDR group(P<0.001 for all);and higher in the PDR group than in the NDR group(P<0.001 for all).In the ROC curve analysis,the NLR,PLR,and SII were significant predictors of DR(P<0.001 for all).The highest area under the curve(AUC)was for the PLR(0.929 for PLR,0.925 for SII,and 0.821 for NLR).Multivariate regression analysis indicated that NLR,PLR,and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM[odds ratio(OR)=1.122,95%confidence interval(CI):0.200–2.043,P<0.05;OR=0.038,95%CI:0.018–0.058,P<0.05;OR=0.007,95%CI:0.001–0.01,P<0.05,respectively).CONCLUSION:The NLR,PLR,and SII may be used as predictors of DR.

Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

On implications of somatostatin in diabetic retinopathy

Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases.Insufficient neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular damage.Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy.Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated.In one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic retinopathy.Overall,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy.In order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be addressed.These include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes.

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus： the Desheng Diabetic Eye Study

AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

Risk factors associated with retinal neovascularization of diabetic retinopathy in type 2 diabetes mellitus

AIM: To evaluate the risk factors associated with retinal neovascularization of diabetic retinopathy in northern Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: The clinical characteristics of 200 patients with proliferative diabetic retinopathy (PDR) and 100 age-matched healthy individuals were compared. The univariate and multivariate logistic regression analysis were performed in the patients with PDR. RESULTS: Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), uric acid (UA), white blood cell count (WBC), absolute neutrophil count, hematocrit (HCT) and mean platelet volume (MPV) and mean platelet volume (MPV) were all significantly higher in patients with PDR than in the control group (P<0.05). The univariate and multivariate logistic regression analysis showed that risk factors independently associated with retinal neovascularization of DR were duration of diabetes mellitus (OR=1.112; P=0.000), BUN (OR=1.277; P=0.000), smoking (OR=3.967; P=0.000) and MPV (OR=2.472; P=0.000). On the other hand, panretinal photocoagulation was associated with reduced risk of retinal neovascularization (OR=0.983; P=0.000). CONCLUSION: Preventing and controlling T2DM in terms of risk factors, including duration of diabetes, BUN, smoking and MPV, might offer novel approaches to prevent or delay the onset of retinal neovascularization in patients with PDR.

Risk factors for diabetic retinopathy in northern Chinese patients with type 2 diabetes mellitus

AIM: To investigate the prevalence and risk factors of diabetic retinopathy (DR) in northern Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective cross-sectional study was performed between May 2011 and April 2012. A total of 1100 patients (male/female, 483/617) were included in this study. DR was defined following the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. All included patients accepted a comprehensive ophthalmic examination including retinal photographs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for age and gender. RESULTS: Retinopathy was present in 307 patients with a prevalence of 27.9%. In univariate logistic analysis, presence of DR was associated with longer duration of diabetes (OR, 5.70; 95% CI, 2.91-12.56), higher concentration of fasting blood glucose (OR, 12.94; 95% CI, 2.40-67.71), higher level of glycosylated hemoglobin HbA1c (OR, 5.50; 95% CI, 3.78-11.97) and insulin treatment (OR, 6.99; 95%Cl, 1.39-35.12). The lifestyle of patients with T2DM including smoking, alcohol consumption and regular exercise seemed not associated with the development of DR. CONCLUSION: Our study suggests that fasting serum glucose concentration, HbA1c level, duration of diabetes and insulin treatment are potential risk factors for DR in northern Chinese patients with T2DM, while the lifestyle of included patients seems not associated with DR.

Epidemiological characteristics and risk factors of diabetic retinopathy in type 2 diabetes mellitus in Shandong Peninsula of China

AIM: To determine the epidemiological characteristics and estimate the risk factors of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) in Shandong Peninsula of China. METHODS: The cases of T2DM admitted to Affiliated Hospital of Medical College of Qingdao University, Shandong Province, China, from January 2006 to December 2010 were retrospectively reviewed. The epidemiological characteristics of DR were estimated. The cases were divided into two groups according to degrees of retinopathy: non-DR group and DR group. Logistic regression analysis was used to study the related risk factors of DR. RESULTS: The prevalence of DR in patients with T2DM was 25.08% (834/3326). There was significant difference between the average age for men (59.08 +/- 15.43 years) and for women (62.92 +/- 18.19 years, P=0.0021). The majority of DR occurred in women (female: male ratio=1.76:1, P<0.0001). The incidence rate of DR in urban (489/834) was higher than that in rural area (345/834, P<0.0001). In 834 DR patients, the mean duration of T2DM was 8.90 +/- 4.15 years (range: 0-16 years); 440 people (52.76%) had received varying degrees of health education about prevention and primary care of DM; and 473 people (56.71%) suffered from other DM complications confirmed at the same time. In addition, the incidence rate of monocular (551/3326) and binocular retinopathy (283/3326) were statistically different (P<0.0001). Factors associated (p<0.05) with the presence of DR included old age, lower health educational level, intraocular surgery history, longer duration of T2DM, accompanying with other DM complications, no standard treatment procedure, lower body mass index (BMI) and higher fasting plasma glucose (FPG), glycated hemoglobin A(1)C (HbA(1)C), urine albumin (UA), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C). The risk factors (P<0.05) independently associated with the presence of DR were: longer duration of T2DM, lower health educational level, higher FPG, higher UA, lower BMI and higher IC. CONCLUSION: DR is highly prevalent in the patients with T2DM in Shandong Peninsula of China. Besides blood glucose, many factors are associated with the present and development of DR.

Diabetes onset at an earlier age and high HbA1c levels as risk factors of diabetic retinopathy

AIM:To assess the effect of age at diabetes onset and uncontrollable high Hb A1 c levels on the development of diabetic retinopathy(DR)among Chinese type 2 diabetes mellitus(DM)patients.METHODS:This was a cross-sectional survey of diabetic patients in Subei district,China.Data covering physical measurements,fasting blood-glucose(FBG),glycosylated hemoglobin(Hb A1 c),blood lipid,urinary albumin/creatinine ratio(UACR),ocular fundus examination,and diabetes treatment records were collected.An independent sample t-test were used to analyze differences.A Logistic regression analysis was applied to study the independent risk factors of DR.RESULTS:A total of 1282 patients with type 2 DM were enrolled,and 191 cases had DR(14.9%).The age at diabetes onset,education level,alcohol consumption,Hb A1 c level,UACR level,and hypoglycemic drugs were independent influencing factors for DR.The older the onset of diabetes,the less likely to develop DR(OR:0.958,95%CI:0.942-0.975,P=0.000).Patients were then divided in terms of age at diabetes onset as follows:<50 y,50-59 y,60-69 y,and≥70 y.Compared with diabetes onset age<50 y,50-59 y(OR:0.463,95%CI:0.306-0.699,P=0.000),60-69 y(OR:0.329,95%CI:0.203-0.535,P=0.000)and≥70 y(OR:0.232,95%CI:0.094-0.577,P=0.002)were at a lower risk of DR.The prevalence of DR was highest in patients with diabetes onset age<50 y(29.5%,P<0.05).The Hb A1 c level(8.67±1.97)%and proportion of insulin injection(52.5%)in patients with diabetes onset<40 y were higher than in patients with older diabetes onset age(P<0.05).CONCLUSION:Diabetes onset at an earlier age and uncontrollable high Hb A1 c level could be independent risk factors for DR.

Meta- analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

AIM: To collectively evaluate the association of intercellular adhesion molecule-1(ICAM-1) gene K469 E polymorphism(rs5498) with diabetic retinopathy(DR) in patients with type 2 diabetic mellitus(T2DM). METHODS: Overall review of available literatures relating K469 E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios(ORs). Potential sources of heterogeneity and bias were explored.RESULTS: Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469 E polymorphism with DR(P 】0.05). A statistically significant association was detected between the K469 E polymorphism and proliferative DR(PDR) in Asians only in dominant model(GG+AG vs AA) with pooled OR of 0.729(95%CI: 0.564-0.942, P=0.016, P heterogeneity=0.143), however, this association was not detected in recessive model(AG +AA vs GG;OR=1.178, 95%CI: 0.898-1.545, P =0.236, P heterogeneity=0.248)or allelic model(G vs A; OR=0.769, 95% CI: 0.576-1.026,P =0.074, P heterogeneity=0.094). No publication bias was found by Funnel plot, Begg’s and Egger’s test. CONCLUSION: This research found no statistically significant association between ICAM-1 gene K469 E polymorphism and DR in patients with T2 DM, but showed significant association of the K469 E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

AIM：To investigate the relationship between Creactive protein（CRP）and diabetic retinopathy（DR）in a cohort of Chinese patients with type 2 diabetes mellitus（T2DM）.·METHODS：Community-based observational cohort study.There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing.Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire,ocular and anthropometric examinations and laboratory investigation.The presence and severity of DR were assessed by seven fields 30°color fundus photographs.Subjects were then classified into groups with no DR,any DR,or vision-threatening DR.CRP was analyzed from serum of study subjects.·RESULTS：A total of 1007 patients with T2DM were included for analysis,including 408（40.5%）men and 599（59.5%）women.The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men（=0.004,OR 0.37,95%CI0.18-0.74）.After adjusting for possible covariates,higher levels of CRP were associated with lower prevalence of any DR（=0.02,OR 0.55,95%CI 0.35-0.89）,but not associated with vision-threatening DR（=0.62,OR 0.78,95%CI 0.28-2.14）.After stratification by sex,the inverse association between CRP and DR was found to be statistically significant in men（=0.006,OR 0.35,95%CI0.16-0.73）,but not in women（=0.58,OR 0.88,95%CI0.29-1.16）.·CONCLUSION：The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR.

Prevalence and risk factors of diabetic retinopathy in patients with type 2 diabetes in Shanghai

AIM:To investigate the prevalence of diabetic retinopathy(DR)in residents of Shanghai and analyze the risk factors of DR.METHODS:This study involved 7233 patients with diabetes in 2016.The demographic data of the participants were collected using a questionnaire survey.Physical examination,laboratory tests,and ophthalmological examinations were conducted.Two professional ophthalmologists diagnosed and graded DR by fundus examination and then combined the results with fundus images.The unconditional multivariate Logistic regression analysis was used to determine the risk factors.RESULTS:In total,6978 patients with type 2 diabetes in Shanghai with a mean age of 68.33±8.40 y were recruited,including 2975 males(42.6%)and 4003 females(57.4%).Overall,1184 patients were diagnosed with DR,with a prevalence rate of 16.97%.Regression analysis showed that duration of diabetes(OR 1.061,95%CI 1.049-1.073),high systolic blood pressure(SBP;OR 1.071,95%CI 1.037-1.106),increased glycosylated hemoglobin level(OR 1.234,95%CI 1.162-1.311),high blood glucose level(OR 1.061,95%CI 1.023-1.099),increased neutrophil-to-lymphocyte ratio(NLR;OR 1.132,95%CI 1.053-1.217)and mean platelet volume(MPV;OR 1.077,95%CI 1.016-1.142)were risk factors of DR.Conversely,hematocrit(HCT;OR 0.971,95%CI 0.954-0.988)and mean corpuscular volume(MCV;OR 0.980,95%CI 0.965-0.994)were protective factors.CONCLUSION:The prevalence rate of DR in Shanghai is 16.97%.The duration of diabetes,high SBP,increased glycosylated hemoglobin,NLR,and MPV were determined as risk factors of DR.

Serum microRNA-221 as a biomarker for diabetic retinopathy in patients associated with type 2 diabetes

AIM: To investigate the candidate microRNA(miRNA), miR-221 as a novel biomarker for diabetic retinopathy(DR) in patients associated with type 2 diabetes(T2D).METHODS: The subjects involved were divided into four groups: healthy control(HC), no diabetic retinopathy(NDR), non-proliferative diabetic retinopathy(NPDR) and proliferative diabetic retinopathy(PDR) group. Serum miR-221 was validated by real-time quantitative reversetranscription polymerase chain reaction(qRT-PCR). Also, serum angiotensin II(Ang II) and vascular endothelial growth factor(VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic(ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang Ⅱ and VEGF for DR in patients with T2D. Spearman’s rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D.RESULTS: Primarily, serum miR-221, Ang Ⅱ and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups(P<0.001). Additionally, miR-221 in serum was remarkably positively correlatedwith metabolic parameters such as glycated hemoglobin(r=0.310, P=0.002) and homeostasis model assessment for insulin resistance(r=0.413, P<0.001), as well as serum markers for instance Ang Ⅱ(r=0.667, P<0.001) and VEGF(r=0.499, P<0.001). Furthermore, serum miR-221(AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang Ⅱ(AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF(AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them.CONCLUSION: Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.

Association of macular pigment optical density with early stage of non-proliferative diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

AIM：To detect the association between macular pigment optical density（MPOD）,which reflects the antioxidant ability of retina,and diabetic retinopathy（DR）and to investigate the correlated factors of MPOD.METHODS： Totally 435 subjects of urban Chinese were recruited to the study and divided into 3 groups： non-diabetes mellitus controls（NDM）,diabetic patients without retinopathy（DWR）,and patients with early stage of non-proliferative diabetic retinopathy（DR）.Demographic and lifestyle characteristics were ascertained by questionnaire.A food-frequency questionnaire,general physical and ophthalmic examinations were completed for all participants.MPOD was measured by heterochromatic flicker photometry.Foveal thickness was measured by optical coherence tomography.The difference of MPOD among 3 groups was analyzed by analysis of covariance.The correlation analyses of MPOD with the candidate influence factors were assessed using the generalized estimating equations（GEE） model.RESULTS： Of the 435 participants,34 could not perform the MPOD measurements.Final analysis included 401 subjects,including 48 were in DR group,134 in DWR group,and 219 in NDM group.MPOD was not significantly different among DR（0.49 ±0.21）,DWR（0.45 ±0.21）,and NDM（0.49±0.17） groups（P=0.24） after adjustment for fasting plasma glycemia,central foveal thickness,green vegetables,Chinese wolfberry,carotene and vitamin E.For all the 401 participants included,MPOD was positively associated with central foveal thickness（E=0.0007,P=0.001）,Chinese wolfberry（E=0.0345,P=0.01）,and green vegetables（E=0.0596,P〈0.001） intake.CONCLUSION： The data suggest that MPOD level is not statistically significantly influenced by the onset of diabetes or early stage of DR in the studied population.MPOD level is positively associated with thicker central foveal thickness and higher intake of foods containing carotenoids.

Prognosis value of Chinese Ocular Fundus Diseases Society classification for proliferative diabetic retinopathy on postoperative visual acuity after pars plana vitrectomy in type 2 diabetes

AIM: To compare the postoperative visual acuity among eyes with proliferative diabetic retinopathy(PDR) of different stages after pars plana vitrectomy(PPV) in type 2 diabetic patients. METHODS: A retrospective study was conducted for PDR eyes undergoing PPV in type 2 diabetic patients. All patients were divided into three groups based on Chinese Ocular Fundus Diseases Society(COFDS) classification for PDR: Group A(primary vitreous hemorrhage), Group B(primary fibrovascular proliferation) and Group C(primary vitreous hemorrhage and/or fibrovascular proliferative combined with retinal detachment). The postoperative visual acuity and the change between postoperative and preoperative visual acuity were compared among three groups. The associated risk factors for postoperative visual acuity were analyzed in the univariate and multiple linear aggression. RESULTS: In total, 195 eyes of 195 patients were collected in this study, including 71 eyes of 71 patients in Group A, 75 eyes of 75 patients in Group B and 49 eyes of 49 patients in Group C. The eyes in Group A got better postoperative best-corrected visual acuity(BCVA) compared to the eyes in Group B and C(0.48±0.48 vs 0.89±0.63, P<0.001;0.48±0.48 vs 1.04±0.67, P<0.001;respectively). The eyes in Group A got more improvement of BCVA compared to the eyes in Group B and C(1.07±0.70 vs 0.73±0.68, P=0.004;1.07±0.70 vs 0.77±0.78, P=0.024;respectively). In the multiple linear regression analysis, primary fibro-proliferative type(β=0.194, 95%CI=0.060-0.447, P=0.01), retinal detachment type(β=0.244, 95%CI=0.132-0.579, P=0.02), baseline log MAR BCVA(β=0.192, 95%CI=0.068-0.345, P=0.004), silicone oil tamponade(β=0.272, 95%CI=0.173-0.528, P<0.001) was positively correlated with postoperative log MAR BCVA. Eyes undergoing phacovitrectomy had better postoperative BCVA(β=-0.144, 95%CI=-0.389 to-0.027, P=0.025). CONCLUSION: PDR eyes of primary vitreous hemorrhage type usually have better visual acuity prognosis compared to primary fibrovascular proliferation type and retinal detachment type. COFDS classification for PDR may have a high prognostic value for postoperative visual outcome and surgical management indications.