Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage

AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

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.

Research on the Correlation Between rs2110385 Polymorphisms of the Visfatin Gene and Nonproliferative Diabetic Retinopathy

Objective:To investigate the association between rs2110385 polymorphisms of the visfatin gene and the risk of type 2 diabetic retinopathy(DR).Methods:172 Han subjects were selected from Xi’an Shaanxi Province;140 patients with type 2 diabetes mellitus(T2DM)and 32 normal controls(NC)were selected from our hospital.Patients with diabetes were divided into a non-DR group(T2DM)(n=69)and a nonproliferative diabetic retinopathy Group(DR)(n=71)after dilated fundus photography and fundus fluorescein angiography.rs2110385/AluⅠgenotypes were detected by standardized polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),and the differences in the detection rates of different genotypes in the above populations were compared.Results:1)The visfatin level in the DR Group was significantly higher than that in the NC and T2DM groups(P<0.05).2)The frequency of GG genotype and G allele of rs2110385 in the DR Group were higher than those in the T2DM and NC groups(80.3,69.6,50.0,86.6,79,65.6,P<0.05).3)There were significant differences in allele frequency and genotype frequency distribution of rs2110385 between the DR Group and the NC group(P<0.01).Conclusion:Visfatin increased in the nonproliferative diabetic retinopathy group and could be a potential indicator for the clinical prediction of DR.The G allele of the rs2110385 polymorphic site may be related to the risk of DR.

Nomogram for predicting non-proliferative vitreoretinopathy probability after vitrectomy in eyes with rhegmatogenous retinal detachment

AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probability.METHODS:A total of 741 patients(741 eyes)diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set.Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-,4-,5-,and 6-month postoperative PVR-free probabilities.Nomogram performance was estimated by the concordance index(C-index),calibration plot,and the area receiver operating characteristic(ROC)curve.RESULTS:A nomogram was constructed based on the preoperative PVR,silicone oil tamponade time(SOTT),photocoagulation energy(PE),retinal tear size(RTS),and hypertension.In the training set,the C-index of the nomogram was 0.896,0.936,0.961,and 0.972 at 3,4,5,and 6mo,respectively.The C-index values in the validation set were 0.860,0.936,0.951,and 0.965 at 3,4,5,and 6mo,respectively.Decision-curve analysis indicated that only the 4-,5-,and 6-month nomograms had significant net benefits over a large threshold probabilities interval.CONCLUSION:Preoperative PVR,SOTT,PE,RTS,and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD.The proposed nomogram can effectively predict the 4-,5-,and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.

Surgical treatment for proliferative diabetic retinopathy with ocular albinism

Dear Editor,We are writing to present an uncommon case of a45-year-old woman with bilateral proliferative diabetic retinopathy (PDR) and ocular albinism (OA).Albinism is a group of inherited disorders of tyrosinase activities and melanin biosynthesis resulting in little or no production of the pigment melanin。

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axis.In summary,Ozurdex provides a potential therapeutic option for traumatic PVR.

Meta analysis and data mining of the method of yishenhuoxue in the treatment of nonproliferative diabetic retinopathy

Objective:To evaluate the efficacy and safety of the method of Yishen Huoxue in the intervention of nonproliferative diabetic retinopathy(NPDR)by Meta analysis and explore the medication regularity of Chinese Medicine(TCM)based on data mining.Methods:The related literature of TCM in the treatment of NPDR published in CNKI,VIP,WF,PubMed,the Cochrane Library,SinoMed,Embase were collected.The quality of the included literature was evaluated with reference to the Cochrane System Evaluators'Handbook,and statistical analysis was performed by applying Revman 5.4.1 software.After normalization of the Chinese medicine names,association rule analysis was performed by using SPSS Modeler 18,and then Cytoscape was used to produce complex network diagrams.Results:20 RCTs were included.Meta-analysis results showed that the method of Yishen Huoxue or Yishen Huoxue combined with western medicine were better than the control group in improving the total clinical efficiency[RR=1.21,95%CI(1.16,1.27),P<0.00001],TCM symptom efficacy[RR=1.28,95%CI(1.18,1.39),P<0.00001],and visual acuity[MD=0.11,95%CI(0.05,0.17),P=0.0001],HDL-C[MD=0.14,95%CI(0.03,0.25),P=0.02];reducing the number of fundus hemangiomas[MD=-3.51,95%CI(-5.73,-1.28),P=0.002],hemorrhagic spot area[MD=-0.70,95%CI(-0.95,-0.46),P<0.00001],CMT[MD=-35.31,95%CI(-55.47,-15.14),P=0.0006],FBG[MD=-0.39,95%CI(-0.72,-0.05),P=0.02],LDL-C[MD=-0.36,95%CI(-0.64,-0.08),P=0.01],whole high blood viscosity[MD=-0.43,95%CI(-0.75,-0.12),P=0.006],plasma viscosity[MD=-0.36,95%CI(-0.67,-0.06),P=0.02]and fibrinogen[MD=-0.50,95%CI(-0.81,-0.19),P=0.002].The differences were statistically significant.The 20 recipes entered involved a total of 70 herbal medicines.It is analyzed that the high-frequency drugs and the core drugsare gou qi,san qi,dan shen,haung qi,sheng di huang,et al.The association rule analysis summarizes the commonly used pairs including:sheng di huang-san qi,sheng di huang-gou qi,et al.Conclusions:Compared with western medicine treatment alone,the method of Yishen Huoxue or Yishen Huoxue combined with western medicine produce better effects,but it still needs to be verified by higher quality clinical studies.

Prevalence of diabetic retinopathy, proliferative diabetic retinopathy and non-proliferative diabetic retinopathy in Asian T2DM patients: a systematic review and Metaanalysis

AIM: To investigate the pooled prevalence of diabetic retinopathy(DR), proliferative DR(PDR) and nonproliferative DR(NPDR) in Asian type 2 diabetes mellitus(T2 DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2 DM patients. Effect size(ES) with 95% confidence interval(CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2 DM patients, respectively. RESULTS: There were 41 references and 48 995 T2 DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2 DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2 DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2 DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients(45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients(74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2 DM from India was higher than patients fromother locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2 DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2 DM patients, and we also recommend suitable interventions to prevent its progression.

Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab

AIMTo evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR).METHODSThis study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively.RESULTSIn PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P&#x0003c;0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P&#x0003c;0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P&#x0003c;0.05) and to patients that did not receive IVB (P&#x0003c;0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P&#x0003c;0.01) or in patients who did not receive IVB treatment (P&#x0003c;0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis.CONCLUSIONWe found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF.

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

AIM： To assess if the included vascular endothelial growth factor （VEGF） polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus （T2DM）. METHODS： A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study （ETDRS） standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts.RESULTS： In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher’s exact test was performed for rs3025021 [OR （95% CI）=0.44（0.08-2.2）; P=0.25] and rs2010963 [OR （95% CI）=0.63（0.25-1.6）; P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows： rs3025021 vs rs3025035： D’=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963： D’=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963： D’=0.505, r2=0.0214, P=0.142.CONCLUSION： This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.

Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

AIM： To evaluate the effects of panretinal photocoagulation （PRP） compared with PRP plus intravitreal bevacizumab （IVB） in patients with high-risk proliferative diabetic retinopathy （PDR） according to the Early Treatment Diabetic Retinopathy Study criteria.METHODS： The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP （PRP group） or PRP plus intravitreal injection of 1.25 mg of bevacizumab （PRP-Plus group）. Patients underwent complete ophthalmic evaluation, including best corrected visual acuity （BCVA）, intraocular pressure （IOP）, and new vessel size in fluorescein angiography （FA） and optical coherence tomography for the assessment of central subfield macular thickness （CSMT） at baseline and at weeks 12 （±2）, 16 （±2）, 24 （±2） and 48 （±2）. Main outcome measures also included vitreous clear-up time and neovascularization on the disc （NVD） regression time. Adverse events associated with intravitreal injection were investigated.RESULTS： Thirty consecutive patients （n=36 eyes） completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations （NVs）, BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group （P〈0.05）. Patients received an average of 1.3 injections （range： 1-2）. Ten eyes （27.8%） underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage （VH）. No major adverse events were identified.CONCLUSION： The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.

Angiogenesis-related cytokines in serum of proliferative diabetic retinopathy patients before and after vitrectomy

AIM: To evaluate serum concentrations of angiogenesis-related cytokines in proliferative diabetic retinopathy (PDR) before and after vitrectomy. METHODS: Serum samples were collected from 30 PDR patients with varying severity before and after vitrectomy. Serum concentrations of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10) were determined by enzyme-linked immunosorbent assays(ELISA). RESULTS: Serum concentrations of VEGF, PEDF, IL-8 and IP-10 were significantly higher in PDR patients than that in controls, respectively (P<0.05). VEGF concentration decreased significantly in postoperative samples than that in preoperative samples (P<0.05). The concentrations of PEDF, IL-8 and IP-10 did not exhibit significant changes after vitrectomy. CONCLUSION: Elevated cytokines levels in serum may be diagnostically useful in PDR. Angiogenesis-related cytokines play important roles in the development of PDR, and would instruct the risk assessment of pathogenetic condition in PDR patients.

Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P 【0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P 【0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.

Effect of focal laser photocoagulation in eyes with mild to moderate non-proliferative diabetic retinopathy

AIM：To report the effect of focal laser photocoagulation on both the severity of hard exudates（HEs） and the rate of disease progression in eyes with mild to moderate non-proliferative diabetic retinopathy（NPDR）.METHODS： We retrospectively reviewed the medical records of 33 patients（60 eyes） who had been diagnosed with mild to moderate NPDR between January 2006 and December 2012.The patients were divided into 2 groups：Group A（38 eyes in 20 patients treated using focal laser photocoagulation） and Group B（treated without laser photocoagulation）.We also reviewed the best corrected visual acuity measurements,and the fundus photographs taken at both baseline and follow-up visits. RESULTS： In Group A,HE severity grade had decreased significantly from baseline to the final visit（P 〈0.05）,but this was not the case in Group B（P =0.662）.The cumulative probabilities of retinopathy progression at 5y were 26% in Group A and 30% in Group B.KaplanMeier survival curves showed no significant difference between the groups with regard to retinopathy progression（P =0.805）.CONCLUSION： Focal laser photocoagulation reduced the levels of HEs in eyes with mild to moderate NPDR.However,the treatment was not able to decelerate the progression of DR.

Effect of intravitreal conbercept treatment before vitrectomy in proliferative diabetic retinopathy

AIM： To evaluate the safety and efficacy of intravitreal conbercept（IVC） injections as pretreatment for pars plana vitrectomy（PPV） in severe proliferative diabetic retinopathy（PDR）. METHODS： This was a retrospective chart review of all patients who underwent PPV for PDR from January 2014 to October 2016. Patients who underwent IVC injection before PPV were assigned to the IVC group; the others were assigned to the control group. The IVC was performed 3-7 d before surgery in the IVC group. All the eyes in the two groups were operated by the same doctor to complete the vitrectomy. Intraoperative complications and the changes in best-corrected visual acuity（BCVA） before and after surgery were compared between the two groups. RESULTS： A total of 68 eyes of 63 patients（22 eyes in the IVC group and 46 eyes in the control group） were examined. The risk of intraoperative bleeding was lower in the IVC group（2/22） than in the control group（25/46, P=0.000）. Furthermore, the use of endodiathermy was significantly lower in the IVC group（1/22） than in the control group（12/46, P=0.047）. The surgical time in the IVC group（112.64±34.52 min） was significantly shorter than in the control group（132.85±40.04 min, P〈0.05）. Compared to the BCVA before surgery, the mean BCVA was significantly improved after surgery for both groups（P〈0.05）. CONCLUSION： PPV is an effective treatment and can improve vision in patients with PDR. Preoperative intravitreal injection of conbercept could reduce the chances of intraoperative bleeding and the use of endodiathermy and shorten the operative time, which are beneficial in the management of PDR.

Ahmed valve implantation for neovascular glaucoma after 23-gauge vitrectomy in eyes with proliferative diabetic retinopathy

·AIM: To report on the outcome of Ahmed glaucoma valve (AGV) implantation for the management of neovascular glaucoma (NVG) after 23 -gauge vitrectomy for proliferative diabetic retinopathy (PDR). ·METHODS: Twelve medically uncontrolled NVG with earlier 23 -gauge vitrectomy for PDR underwent AGV implantation. The control of intraocular pressure (IOP), preoperative and postoperative best -corrected visual acuity, the development of intraoperative and postoperative complications were evaluated during the follow-up. ·RESULTS: The mean follow-up was 15.4±4.3 months (9-23 months). Mean preoperative IOP was 49.4±5.1mmHg and mean postoperative IOP at the last visit was 17.5 ± 1.6mmHg. The control of IOP was achieved at the final follow -up visits in all patients, however, 8 of 12 patients still needed anti-glaucoma medication (mean number of medications, 0.8±0.7). The visual acuity improved in nine eyes, and the visual acuity unchanged in three eyes at the final follow -up visits. The complications that occurred were minor hyphema in three eyes, choroid detachment in two eyes, and the minor hyphema and choroid detachments were reabsorbed without any surgical intervention. ·CONCLUSION: AGV implantation is a safe and effective procedure that enables successful IOP control and vision preservation in the NVG patients with the history of earlier 23-gauge vitrectomy for PDR.·

Increased interleukin-26 expression in proliferative diabetic retinopathy

AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain reaction.RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs.CONCLUSION: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.

Osteopontin expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy

AIM: To analyze osteopontin (OPN) expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy (PVR). METHODS: A total of 54 vitreous fluid samples were obtained between 2009 and 2010, which contained 45 with PVR (group A) and 9 without PVR (group B). Enzyme-linked immunosorbent assay was applied to quantify the OPN concentrations in vitreous fluid. Four samples of proliferative retinal membrane were also obtained at the time of vitrectomy, and their contents of OPN were measured by Real-time RT-PCR. RESULTS: The OPN levels in the vitreous fluid were 778.48+/- 62.06ng/mL in group A and 452.99 32.52ng/mL in group B. The vitreous OPN levels in group A were significantly higher than those in group B and to rise by time in the early stages of PVR. The average OPN levels in the proliferative retinal membranes (F =0.14) were also higher than those in the retinal pigment cells (F =0) using Real-time RT-PCR. CONCLUSION: The high vitreous and proliferative retinal membrane OPN levels in PVR suggest that OPN might promote the development of PVR. The vitreous OPN concentrations are rising by the time in the early phases of PVR.

Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy

AIMTo examine phosphorylation of alphaB-crystallin (p-&#x003b1;BC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-&#x003b1;BC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR).METHODSEleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-&#x003b1;BC, VEGF, CD31, and p-p38 MAPK antibodies.RESULTSImmunoreactivity for p-&#x003b1;BC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-&#x003b1;BC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-&#x003b1;BC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes.CONCLUSIONPhosphorylation of &#x003b1;BC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.