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.

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.

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.

Use of Cataract Surgery in Urban Beijing: a Post Screening Follow-up of the Elderly with Visual Impairment due to Age-related Cataract

Objective To understand the perception for the use of cataract surgical services in a population acceptors and non-acceptors of cataract surgery in urban Beijing. Methods From a community-based screening program a total of 158 patients with presenting visual acuity of less than 6/18 on either eye due to age-related cataract were informed about the possibility of surgical treatment. These patients were interviewed and re-examined 36 to 46 months after initial screening. The main reasons for not accepting surgery were obtained using a questionnaire. Vision function and vision-related quality of life scores were assessed in those who received and did not receive surgery. Results At the follow-up examination 116 of the 158 patients were available and 36 （31.0%） had undergone cataract surgery. Cases who chose surgery had higher education level than those who did not seek surgery （OR=2.64, 95% CI： 1.08-6.63, P=0.02）. There were no significant differences in vision function （P=0.11） or quality of life scores （P=0.16） between the surgery group and the non-surgery group. Main reasons for not having surgery included no perceived need （50.0%）, feeling of being ＂too old＂ （19.2%）, and worry about the quality of surgery （9.6%）. Cost was seeking surgery. cited by 1 （1.9%） subject as the main reason for not

Association of candidate gene polymorphisms with diabetic retinopathy in Chinese patients with type 2 diabetes

●AIM:To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy(DR)in an urban community cohort of Chinese patients with type 2 diabetes mellitus(T2 DM).●METHODS:A population-based cross-sectional study.The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy(PDR),non-proliferative diabetic retinopathy(NPDR),or diabetic without any retinopathy(DWR)based on the fundus photography and duration of diabetes.Six candidate genes,including advanced glycation end product specific receptor(AGER),aldose reductase(AKR1 B1),inducible nitric oxide synthase(i NOS),pigment epithelium derived factor(PEDF),tumor necrosis factor-alpha(TNF-α),and paraoxonase 1(PON1),were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression.The allele and genotype distribution of 21 functional singlenucleotide polymorphisms(SNPs)in those 6 candidate genes were investigated using MassARRAY genotyping system.●RESULTS:Among 1461 diabetic patients recruited from community,569 were selected in following genotyping analysis,including 97 patients with PDR,217 with NPDR,and 255 with DWR.For the promoter variant rs1051993 in AGER gene,the distribution of allele and genotype in PDR group differed from that in DWR group(allele:P=0.011;genotype:P=0.01).Compared with DWR,patients with PDR had lower frequencies of heterozygous genotype GT(9.8%for DWR,1%for PDR,OR:0.10,95%CI:0.01-0.72)and minor allele T(4.9%for DWR,0.5%for PDR,OR:0.10,95%CI:0.01-0.75).In multivariate model,the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group(GT vs GG:OR:0.07,95%CI:0.01-0.61,P<0.001).No association with DR was observed in other genotyped SNPs.●CONCLUSION:The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.

Association of C(-106)T Polymorphism in Aldose Reductase Gene with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes Mellitus

Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit^cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.

Association of choroidal thickness with early stages of diabetic retinopathy in type 2 diabetes

AIM：To assess the correlation between choroidal thickness（CT） and the early stages of diabetic retinopathy（DR） in type 2 diabetic patients.METHODS：We divided 83 diabetic patients（51-80 years of age;50 females） into non diabetic retinopathy group（NDR） and mild/moderate nonproliferative diabetic retinopathy（NPDR） group,and compared them with 26 non-diabetic control subjects（51-78 years of age;16 females）.Subfoveal choroidal thickness（SFCT） and parafoveal choroidal thickness（PFCT） were measured using enhanced depth imaging spectral-domain optical coherence tomography（EDI-OCT）.Ocular health status,disease duration,body mass index,and hemoglobin A1c（Hb A1c） were recorded.RESULTS：The mean ages of the NDR,NPDR,and control groups were 68.0±6.9y,67.8±6.4y,and 65.1±6.3y,respectively（P=0.17）.Pearson correlation of the right and left eyes for the control subjects was 0.95 and for the NDR subjects was 0.93.SFCT for the right eyes of the controls was 252.77± 41.10 μm,which was significantly thicker than that of the right eyes in NDR group（221.51±46.56 μm） and the worse eyes of the NPDR group（207.18±61.87 μm;ANOVA,P〈0.01）.In the diabetic patients pooled together,age was the only variable significantly associated with SFCT（multiple linear regression analysis,P=0.01）.CONCLUSION：CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with the control eyes.Age is significantly associated with SFCT in the diabetic patients.Diabetic choroidopathy may be present before clinical retinopathy.

Outcomes of small gauge pars plicata vitrectomy for patients with persistent fetal vasculature:a report of 105 cases

AIM：To evaluate the surgical outcomes in eyes with persistent fetal vasculatures（PFV） managed by small gauge pars plicata vitrectomy.METHODS：Consecutive patients with PFV treated by small gauge pars plicata vitrectomy at Beijing Tongren Eye Center between January 2010 and January 2013 were retrospectively reviewed.RESULTS：A total of 118 eyes of 105 patients with PFV were included and undergone small gauge pars plicata vitrectomy,of which 84（71.2%） eyes had lensectomy and 16（13.6%） eyes had lens aspiration and immediate intraocular lens implantation.The percentage of sutured scleral incision of 23 gauge vitrectomy（71.7%,33/46） was higher than that of the 25 gauge vitrectomy（18.1%,13/72）.At last follow-up,visual acuity remained stable in 34 eyes（28.8%） and improved in 84 eyes（71.2%）.Age at surgery（less than 2 y）,anterior type of PFV,and immediate IOL implantation were associated with postoperative improved visual acuity.Sixty five（55.1%） eyes had retinal detachment preoperatively,among which 33（50.8%,33/65） eyes had retinal reattachment or partial retinal reattachment.CONCLUSION：The results suggest that cases with PFV have a potential for developing good visual acuity after small gauge pars plicata vitrectomy with favorable anatomic outcomes and acceptable rate of serious surgical complications.

Retinal vessels caliber changes after strabismus surgery：results of 6mo follow-up

AIM：To evaluate the effect of strabismus surgery on retinal vessels calibers with digital color fundus photographs.METHODS：Two hundred consecutive strabismus patients underwent surgery,and 118 patients（female/male,55/63） who finished 6-month follow-up were finally included in this study.Optic disc-centered digital color fundus photographs of both eyes of all patients were taken prior to surgery and 6mo post surgery.The retinal vascular caliber of 116 operated eyes were measured using the computer program IVAN.The operated eyes were divided into 3 groups according to the surgical methods,recession of one muscle,one muscle recession and one muscle folding,one muscle resection and one muscle recession.The effect of number of altered muscles on retinal vessels was analyzed using statistic software SPSS 16.0.RESULTS：The mean age was 12.4±8.6y.Averaged central retinal artery equivalent（CRAE） of all patients was 120.31 ±23.02 μm preoperatively,and 122.87 ±15.93 μm six months after surgery.Averaged central retinal vein equivalent（CRVE） was 171.11 ±31.73 μm preoperatively and175.02±21.00 μm postoperatively.There was no significant difference of averaged CRAE（P=0.22） or CRVE（P=0.19）before and after operation.Averaged arteriole to venule ratio（AVR） was 0.71 ±0.07 before surgery and 0.70±0.07 after surgery.Comparison of preoperative and postoperative retinal vessels calibers among different surgical groups did not show significant differences.Also,there was no advantage of rectus muscle folding to muscle resection.CONCLUSION：Up to 6mo after strabismus surgery,the retinal vascular calibers were not altered.No more than two muscles in one surgery are safe for retinal perfusion.

The Beijing Desheng Diabetic Eye Study:rationale,design,methodology and baseline data

AIM： To present the rationale, design, methodology, and the baseline data of the Beijing Desheng Diabetic Eye Study（BDDES）, and to determine the prevalence of diabetic retinopathy（DR） and possible risk factors in patients with type 2 diabetes mellitus（T2DM） in an urban community of Beijing, China.METHODS： Community-based prospective cohort study of persons diagnosed with T2DM aged 30 y or older. The main variables of interest are the presence and progression of DR as determined by the standardized ETDRS grading of seven fields fundus photographs. The presence and severity of DR were analyzed for possible correlations to non-genetic and genetic dispositions.RESULTS： A total of 1438 participants with data available for analysis, the prevalence of any DR was 35.4%. The prevalence of mild non-proliferative diabetic retinopathy（NPDR）, moderate NPDR, severe NPDR, and proliferative diabetic retinopathy was 27.7%, 2.6%, 0.5% and 4.5%, respectively. By multiple logistic regression analysis, risk factors for the presence of any DR included male（P=0.031）, lower income level（P=0.011）, lower education background（P=0.022）, longer duration of diabetes（P=0.001）, younger age at diabetic onset（P=0.001）, higher systolic blood pressure（P=0.007）, higher glycosylated hemoglobin A1 c levels（P=0.001）, high albuminuria（P=0.03）, and use of insulin（P〈0.001）. For vision-threatening DR, four factors were significant： younger age at diabetic onset（P〈0.001）,higher systolic blood pressure（P=0.042）, high albuminuria（P〈0.001）, and use of insulin（P〈0.001）. CONCLUSION： The BDDES is the first large-scale ongoing cohort study of a Chinese urban population of persons with type 2 diabetes. Using standardized grading system comparable to large cohort studies from western populations, our baseline data shows that the prevalence of DR and major risk factors in this Chinese ethnic population are comparable to that found in the western population studies.

Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration

AIMTo measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD).METHODSCross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography.RESULTSMPOD of 225 participants (122 healthy and 103 early AMD) was 0.48&#x000b1;0.18. Patients with early AMD (0.52&#x000b1;0.19) tended to have higher MPOD levels than healthy people (0.47&#x000b1;0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01).CONCLUSIONOur findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels.

The diurnal variation pattern of choroidal thickness in macular region of young healthy female individuals using spectral domain optical coherence tomography

AIM： To investigate the pattern of diurnal variations of choroidal thickness of macular region of healthy individuals. ~ METHODS： A prospective study of 32 healthy female subjects was conducted. Each subject underwent 1） a questionnaire on daily schedule, 2） the Pittsburgh Sleep Quality Index questionnaire （PSQI）, and 3） ocular examinations including an eye dominance test, fundus photography, and sequential optical coherence tomography （OCT） imaging, on two separate days at five fixed 3h time intervals. Choroidal thickness was measured by two masked graders. RESULTS： A significant diurnal variation of choriodal thickness at fovea （P〈0.001）, at 500 μm nasal （P〈0.001）, temporal to fovea （P=0.01） or 1500 μm nasal to fovea （P= 0.001） was observed. The median choroidal thickness peaked at 11：00 at fovea （P=0.01）, at 500μm nasal （P = 0.009） and temporal （P=0.03） to fovea. The median amplitude of foveal choroidal thickness was 20.5 pm （13, 31） and 20.0 μm （12.5, 28.2） for the first and second series of measurements, respectively. The greater amplitude of foveal choroidal thickness was associated with thickner initial foveal choroidal thickness [ 0.05 （0.03, 0.08）, P= 0.01], dominant eye 10.51 （4.02, 14.60）, P=0.04] in the multivariate linear regression. CONCLUSION： Our data show a significant diurnal variation of the choroidal thickness at fovea, at 500 μm nasal and temporal to fovea and 1500 μm nasal to fovea. Thicker initial foveal choroidal thickness and being dominant eye may influence the amplitude of foveal choroidal thickness.

Combined photodynamic therapy and ranibizumab for polypoidal choroidal vasculopathy：a 2-year result and systematic review

AIM：To report a cohort of patients with polypoidal choroidal vasculopathy（PCV）treated with photodynamic therapy（PDT）followed by intravitreal ranibizumab injection 24-48 h later,and to compare the results between eyes with PCV treated by PDT followed by intravitreal anti-vascular endothelial growth factor（VEGF）injection and intravitreal anti-VEGF injection followed by PDT by Meta-analysis.METHODS：Retrospective study and systematic literature review. Medical records of patients with PCV who were initially treated using PDT followed by intravitreal ranibizumab injection 24-48 h after PDT and had completed at least 2y follow-up were reviewed and analyzed. Clinical data,including age,sex,best-corrected visual acuity（BCVA）,fundus photograph,fluorescein angiography,indocyanine green angiography and optical coherence tomography were investigated. A systematic literature review was also conducted,and a visual outcome of studies over 1y was compared using Meta-analysis. RESULTS：A total of 52 patients were included in the study. Mean BCVA at baseline and follow-up at 1 or 2y were 0.71± 0.61,0.51±0.36 and 0.68±0.51 log MAR,respectively. The cumulative hazard rate for recurrence at 1 and 2y followup was 15.4% and 30.3% respectively. The percentage of eyes with polyps regression at 3,12 and 24 mo follow-up was 88.5%,84.6% and 67.3% respectively. A Meta-analysis based on 22 independent studies showed the overall vision improvements at 1,2 and 3y follow-up were 0.13±0.04（P〈0.001）,0.12±0.03（P〈0.001）,0.16±0.06（P〈0.001）,respectively. The proportion of polyps regression at 1y follow-up was 64.6%（95%CI：51.5%,77.7%,P〈0.001）in 434 eyes treated by intravitreal anti-VEGF agents beforePDT and 76.0%（95%CI：64.8%,87.3%,P=0.001）in 199 eyes treated by intravitreal anti-VEGF agents after PDT. CONCLUSION：Intravitreal ranibizumab injection 24-48 h following PDT effectively stabilizes visual acuity in the eye with PCV. PDT followed by intravitreal anti-VEGF agents may contribute to a relatively higher proportion of polyps＇ regression as compared to that of intravitreal anti-VEGF before PDT.

Visual impairment with possible macular changes after a high dose of sildenafil in a healthy young woman

Dear Editor,Sildenafil citrate（Viagra;Pfizer Pharmaceuticals,New York,NY,USA）,a selective inhibitor of phosphodiesterase type 5（PDE-5）,is widely used for erectile dysfunction.Its clinical recommended dosage is 25 to 100 mg per day.