Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Impact of COVID-19-related lifestyle changes on diabetic macular edema

AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office visits.METHODS:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021.Period 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was March 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).Main outcome measures included visual acuity,body mass index(BMI),blood pressure(BP),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DME treatment(s)received at each visit.To facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT imaging.RESULTS:There was no change of BMI,systolic BP,and diastolic BP between any of the time periods.HbA1c showed a very small increase from period 1(7.6%)to period 2(7.8%,P=0.015)and decreased back to 7.6%at period 3(P=0.12).Macular thickness decreased for 100%of macular regions.The central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(P=0.0045).After analysis of multiple variables including HbA1c,BMI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in DME.CONCLUSION:DME doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant improvement.While identifying a mechanism behind our findings is beyond the scope of this study,potential explanations may include a delay in retinal changes beyond our study period,an unexpected increase in treatment frequency despite pandemic restrictions,and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.

Effectiveness of intravitreal ranibizumab for diabetic macular edema in vitrectomized versus non-vitrectomized eyes:a Meta-analysis

AIM:To evaluate the effectiveness and safety of intravitreal ranibizumab(IVR)for diabetic macular edema(DME)in vitrectomized versus non-vitrectomized eyes.METHODS:The PubMed,EMBASE,Web of Science,Cochrane,EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME.Clinical outcomes of best-corrected visual acuity(BCVA),central macular thickness(CMT),the mean number of intravitreal injection and adverse events were extracted and analyzed.RESULTS:Six studies involving 641 eyes were included.Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits(P<0.05).Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo[mean difference(MD)=53.57,95%confidence interval(CI):28.03 to 78.72,P<0.0001]and 12mo(MD=49.65,95%CI:19.58 to 79.72,P=0.01),no significant difference was detected in improvement in BCVA at either 6mo(MD=0.05,95%CI:-0.02 to 0.13,P=0.14)or 12mo(MD=0.03,95%CI:-0.04 to 0.09,P=0.43).Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period(MD=0.60,95%CI:0.16 to 1.04,P=0.008),while there was no statistically significant difference between the two groups during 12mo of follow-up.CONCLUSION:Evidence from current study suggests that IVR was useful for both vitrectomized group and nonvitrectomized group with DME.Although less reduction in macular thickness is found in vitrectomized group,visual improvement between two groups is similar.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema:optical coherence tomography and optical coherence tomography angiography

AIM:To analyze the relationship between optical coherence tomography(OCT)and OCT angiography(OCTA)imaging in patients with diabetic macular edema(DME)who are treated with a combination of aflibercept and triamcinolone acetonide(TA).METHODS:A total of 76 eyes newly diagnosed DME were included in this study.They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA.Injections once a month for a total of three injections.Central macular thickness(CMT),number of hyperreflective foci(HRF),height of subretinal fluid(SRF),and area of foveal avascular zone(FAZ)were evaluated using OCT and OCTA at baseline and after each monthly treatment.RESULTS:Both groups showed improvement in best corrected visual acuity(BCVA)and reduction in macular edema after treatment,and the difference in BCVA between the two groups was statistically significant after each treatment(P<0.05).The difference in CMT between the two groups was statistically significant after the first two injections(P<0.01),but not after the third injection(P=0.875).The number of HRF(1mo:7.41±8.25 vs 10.86±7.22,P=0.027;2mo:5.33±6.13 vs 9.12±8.61,P=0.034;3mo:3.58±3.00 vs 6.37±5.97,P=0.007)and height of SRF(1mo:82.39±39.12 vs 105.77±42.26μm,P=0.011;2mo:36.84±10.02 vs 83.59±37.78μm,P<0.01;3mo:11.57±3.29 vs 45.43±12.60μm,P<0.01)in combined group were statistically significant less than aflibercept group after each injection,while the area of FAZ showed no significant change before and after treatment in both groups.CONCLUSION:The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF.However,both aflibercept and combination therapy show no significant change in the area of FAZ.

Guidelines from an expert panel for the management of diabetic macular edema in the Malaysian population

AIM:To derive a Malaysia guideline and consensus as part of the Malaysia Retina Group's efforts for diagnosis,treatment,and best practices of diabetic macular edema(DME).The experts'panel suggests that the treatment algorithm to be divided into groups according to involvement the central macula.The purpose of DME therapy is to improve edema and achieve the best visual results with the least amount of treatment load.METHODS:On two different occasions,a panel of 14 retinal specialists from Malaysia,together with an external expert,responded to a questionnaire on management of DME.A consensus was sought by voting after compiling,analyzing and discussion on first-phase replies on the round table discussion.A recommendation was deemed to have attained consensus when 12 out of the 14 panellists(85%)agreed with it.RESULTS:The terms target response,adequate response,nonresponse,and inadequate response were developed when the DME patients'treatment responses were first characterized.The panelists reached agreement on a number of DME treatment-related issues,including the need to classify patients prior to treatment,firstline treatment options,the right time to switch between treatment modalities,and side effects associated with steroids.From this agreement,recommendations were derived and a treatment algorithm was created.CONCLUSION:A detail and comprehensive treatment algorithm by Malaysia Retina Group for the Malaysian population provides guidance for treatment allocation of patients with DME.

Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines

BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.

Morphological and functional changes in the macular area in diabetic macular edema after a single intravitreal injection of aflibercept

AIM:To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema(DME)using optical coherence tomography angiography(OCTA)and MP-3 microperimetry.METHODS:Twenty-eight patients(42 eyes)diagnosed with DME were treated with intravitreal injection of aflibercept.The changes in best corrected visual acuity(BCVA),central retinal thickness(CRT),foveal avascular zone(FAZ)area,vessel density of superficial retinal capillary plexus(SVD),vessel density of deep retinal capillary plexus(DVD),mean light sensitivity(MLS),2°fixation rate(P1),4°fixation rate(P2),and other indicators 1mo after treatment were compared;of these,BCVA was conver ted into logarithm of the minimum angle of resolution(logMAR),and the correlation among the factors was analyzed.RESULTS:After treatment,logMAR BCVA was 0.47±0.24,which was significantly better than that before treatment(0.63±0.28,P<0.001).The CRT was 359.21±107.87μm after treatment,which was significantly lower than before treatment(474.10±138.20μm,P<0.001).The FAZ area,SVD,and DVD were not significantly changed after treatment compared with the baseline.MLS was 22.16±4.20 dB after treatment,which was significantly higher than before treatment(19.63±4.23 dB,P<0.001).P2 significantly increased after treatment than before treatment(P=0.007).P1 had no significant change after treatment than before treatment(P=0.086).CONCLUSION:A single intravitreal injection of aflibercept effectively reduces macular edema and improves retinal sensitivity,fixation stability,and visual acuity,possibly without causing significant changes in the retinal vascular condition in a short time.

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion

AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:This is a retrospective case control study.The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor(VEGF)for patients diagnosed with macular edema secondary to DR(DME)or RVO(RVO-ME)at Xijing Hospital from August 2021 to July 2022.Meanwhile,aqueous humor samples during vitrectomy from patients with idiopathic macular hole(IMH)were also collected and served as controls.The aqueous humor concentrations of VEGF,platelet-derived factor(PDGF),interleukin(IL)-6,IL-8,IL-18,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured with Human Premixed Multi-Analyte Kit(Luminex).The difference of the aqueous cytokines and the correlation between the two diseases were analyzed.RESULTS:A total of 40 eyes of 38 patients were enrolled in the study,including 13 eyes of 11 DME patients(DME group),16 eyes of 16 RVO-ME patients(RVO-ME group)and 11 eyes of 11 IMH patients(control group).The VEGF,PDGF,IL-6,IL-8,and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group(all P<0.05),the levels of TNF-αwas higher in the DME group than in the control group(P<0.05).The VEGF,IL-6,MCP-1,and TNF-αlevels in the aqueous humor were significantly higher in the DR group than those in the RVO group(all P<0.05).Correlation analyses revealed that there were complex positive correlations between IL-6,IL-8,IL-18,MCP-1,and TNF-αlevels in the aqueous humor of eyes with two diseases.CONCLUSION:Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME,the roles of these factors are more significant or more likely to be activated in DR patients,suggesting different treatment strategies should be considered for the two diseases.

AB010.Promotion of BMP9/ALK1 quiescence signaling for the prevention of diabetic macular edema(DME)

Background:Sight-threatening diabetic macular edema(DME)is caused by increased microvascular permeability.While few direct vascular targeting strategies are available,VEGF pathway inhibition has shown to be effective in reducing retinal vascular leakage but is associated with non-negligible side effects.Thus,more options are needed.Vascular specific Activin-like kinase receptor type I(ALK1)pathway and its circulating ligand Bone morphogenetic protein-9(BMP9)is known for its potent quiescent and stabilizing effect on the vasculature.However,little is known about this pathway in the context of microvascular permeability associated with diabetes.We hypothesize that BMP9/ALK1 pathway is inhibited in diabetic(DB)retinas leading to vascular destabilization and leakage and that its activation could re-establish proper vascular endothelial barrier functions(EBF).Methods:The effect of hyperglycemia(i.e.,HG>10 mM of D-glucose)on Alk1 signaling was evaluated in vitro by subjecting endothelial cells(EC)to increasing concentrations of D-glucose(5,11,25 mM)and in vivo using DB mice(Streptozotocin-induced diabetes).The contribution of Alk1 signaling on EBF was evaluated using Evans Blue permeation in inducible endothelial specific Alk1 KO mice.To evaluate the potential protective effects of BMP9/Alk1 signaling on EBF,BMP9 overexpression was achieved using adenoviral delivery in DB mice.Statistical-One-Way ANOVA or Student’s t-test was used.Results:Endothelial tissue from DB mice showed a significant inhibition of BMP9/ALK1-canonical Smad1,5,8 quiescence signaling(DB n=5;CTL n=4;P<0.01),which was associated with reduced expression of target genes(JAG1,Id1,3,Hey1,2&HES).Moreover,we showed that retinal hyperpermeability associated with diabetes was exacerbated in Alk1 heterozygote mice(n=4-9/group;P<0.0001).Finally,we demonstrated that activation of Alk1 signaling in ECs prevented vascular permeability induced by HG,both in vitro(n=3;P=0.009)and in vivo(n=4-9/group;P<0.0001).Conclusions:Consistent with our hypothesis,vascular stability and quiescence induced by BMP9-ALK1 signaling is inhibited in the DB/HG endothelium which could be an important factor in vascular leakage leading to DME.Our results show that activation of this pathway could offer a therapeutically interesting future option to slow down the onset of DME.

Bevacizumab for the management of diabetic macular edema

Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population and is relatedto 1%-5% of cases of blindness worldwide. Diabetic macular edema (DME) is the most frequent cause of DR vision loss and is an important public health problem. Recent studies have implicated vascular endothelial growth factor (VEGF) in DR and DME pathogenesis, as well as provided evidence of the benefits of anti-VEGF agents for the management of such conditions. Despite the benefits of intravitreal ranibizumab injection for the management of DME, the cost-effectiveness of intravitreal bevacizumab therapy has gained increasing interest in the scientific community. This review summarizes the studies examining bevacizumab for the management of DME, focusing on the efficacy and duration of the clinical benefits of decreasing DME and the improvement of best-corrected visual acuity (BCVA). There is strong evidence that intravitreal bevacizumab injection therapy has a good cost-effective profile in the management of DME and may be associated with laser photocoagulation; however, its clinical superiority in terms of the duration of DME regression and the improvement of BCVA compared with intravitreal ranibizumab and other intravitreal anti-VEGF therapies remains unclear and deserves further investigation.

Managing diabetic macular edema: The leading cause of diabetes blindness

Diabetic macular edema (DME) is the leading cause of blindness in young adults in developed countries, affecting 12% of type 1 and 28% of type 2 diabetic patients. The gold standard DME treatment should be based on a good control of glycemia along with control of lipids and renal function. However, despite the systemic metabolic control values being essential for patients with diabetic retinopathy (DR), it has proven to be insufficient for DME if it appears. With these patients, additional measures are needed in order to avoid the subsequent loss of vision. While laser treatment of DME has been the only valid treatment so far, it has been inadequate in chronic cases. The introduction of new treatments, such as intravitreal corticosteroids or anti-VEGF drugs, have recently shown their safety and efficacy and together with laser photocoagulation are becoming the treatments of choice in the management of DME.

Clinical trials on corticosteroids for diabetic macular edema

Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.

Comparison of conbercept and ranibizumab for the treatment efficacy of diabetic macular edema: a Metaanalysis and systematic review

AIM: To evaluate the efficacy of intravitreal injection of conbercept(IVC) and ranibizumab(IVR) in patients with diabetic macular edema.METHODS: Reviewers have searched 12 databases, including PubMed, Medline, EMBASE, Web of Science, Springer, ScienceDirect, OVID, Cochrane Library, Clinical Trials.gov, cqVIP, WanFangdata and China National Knowledge Infrastructure(CNKI), up to December 28, 2018. Rev Man 5.3(Cochrane Library Software, Oxford, UK) was employed for statistical analysis. Fixed and random effects models were applied to assess heterogeneity. Odds ratio(OR) was applied for dichotomous variables;weighted mean difference(WMD) was applied for continuous variables. The confidence interval(CI) was set at 95%. Central macular thickness(CMT) and best-corrected visual acuity(BCVA) were employed to analyze the improvement of DME patients. Inclusion criteria for picking out studies were retrospective studies and randomized controlled trials(RCTs) that compared IVC and IVR for the treatment of diabetic macular edema.RESULTS: Four retrospective studies and five RCTs were included with a total of 609 patients. No statistically significant difference was observed in mean CMT and mean BCVA in the baseline parameters [BCVA(WMD:-0.48;95%CI:-1.06 to 0.10;P=0.1), CMT(WMD:-0.83;95%CI:-15.15 to 13.49;P=0.91). No significant difference was found in the improvement of BCVA and adverse event(AE) in IVC group, compared with IVR group after treatment of loading dosage [the 1 st month BCVA(WMD: 0.01;95%CI:-0.26 to 0.27;P=0.96), the 3 rd month BCVA(WMD:-0.04;95%CI:-0.14 to 0.06;P=0.46);the 6 th month BCVA(WMD:-0.24;95%CI:-1.62 to 1.14;P=0.73)], AE(OR: 0.84;95%CI: 0.38 to 1.84;P=0.66)]. A slight difference was found in the effectiveness rate(OR: 1.70;95%CI: 0.97 to 2.96;P=0.06), There were statistically significant differences between IVC and IVR treatment in terms of CMT (1 st month CMT(WMD:-19.88;95%CI:-27.94 to-11.82;P<0.001), 3 rd month CMT(WMD:-23.31;95%CI:-43.30 to-3.33;P=0.02), 6 th month CMT(WMD:-74.74;95%CI:-106.22 to-43.26;P<0.001))CONCLUSION: Pooled evidence suggests that both IVC and IVR are effective in the therapy of diabetic macular edema and affirms that IVC presents superiority over IVR therapy in regard of CMT in patients with diabetic macular edema, but no statistically significant difference with regard to visual improvement. Relevant RCTs with longerterm follow-up are necessary to back up our conclusion.

Classification of diabetic retinopathy and diabetic macular edema

The global incidence and prevalence of diabetes mellitus(DM)have reached epidemic proportions.Estimates indicate that more than 360 million people will be affected by DM by 2030.All of these individuals will be at risk of developing diabetic retinopathy(DR).It is extremely important to categorize,classify and stage the severity of DR in order to establish adequate therapy.With proper management more than 90%of cases of visual loss can be prevented.The purpose of the current paper is to review the classification of DR with a special emphasis on the International Clinical Disease Severity Scale for DR.This new classification is simple to use,easy to remember and based on scientific evidence.It does not require specialized examinations such as optical coherence tomography or fluorescein angiography.It is based on clinical examination and applying the Early Treatment of Diabetic Retinopathy Study 4:2:1 rule.

Vascular endothelial growth factor trap-eye(Aflibercept) for the management of diabetic macular edema

Diabetic retinopathy(DR)is the most common cause of visual loss among working age individuals.Diabetic macular edema(DME)is an important complication of DR that affects around one third of the patients with DR.Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor(VEGF)antagonists.The index review discusses aflibercept(EYLEA-Regeneron Pharmaceuticals,Inc.,Tarrytown,New York,NY,and Bayer Healthcare Pharmaceuticals,Berlin,Germany)in the context of other VEGF antagonists currently available for the treatment of DME.A systematic search of literature was conducted on PubMed,Scopus,and Google Scholar with no limitation on language or year of publication.Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A(VEGF-A)along with a longer duration of action as compared to other VEGF antagonists.Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring.Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases.However,further studies are indicated to confirm the role,safety,and efficacy of aflibercept for DME.

Macular laser photocoagulation with or without intravitreal triamcinolone pretreatment for diabetic macular edema： a result from five randomized controlled trials

AIM：To assess possible benefits of intravitreal triamcinolone acetonide（IVTA）injection as pretreatment for macular laser photocoagulation（MLP）in patients with diabetic macular edema（DME）.·METHODS：Published randomized controlled trials（RCTs）concerning MLP with or without IVTA pretreatment for DME were retrieved from databases CNKI,Medline,EMbase,Web of Science,and the Cochrane Library.A Meta-analysis on eligible studies was conducted using Rev Man 5.0 software.Two investigators independently assessed the quality of the trials and extracted data.Main outcome measures included the change in best-corrected visual acuity（BCVA）,difference in central macular thickness（CMT）and adverse events reporting in particular elevated intraocular pressure within the follow-up period.The results were pooled using weight mean difference（WMD）or odds risk（OR）with their corresponding 95%confidence intervals（CI）.A fixed-or random-effect model was employed depending on the heterogeneity of the inclusion trials.·R ESULTS：Finally,five independent RCTs were identified and used for comparing MLP with IVTA pretreatment（131 eyes）with MLP alone（133 eyes,control group）.The overall study quality was relatively higher according to the modified Jadad scale.The Metaanalysis showed that MLP with IVTA pretreatment significantly reduced CMT at one,three and six months（=0.002,0.0003 and 0.04,respectively）,compared with MLP alone.The IVTA pretreatment group showed statistically significant improvements in BCVA at the one-month follow up as compared with the control group（=0.03）.At three-and six-month follow up,there was a beneficial trend towards improving visual acuity in the IVTA pretreatment group without statistical significance between groups（=0.06 and 0.20,respectively）.The incidence of elevation of intraocular pressure was significantly higher in the IVTA pretreatment group than in the control group（〈0.0001）.No evidence of publication bias was present according to Begg’s test and Egger’s test.There was a low level of heterogeneity in the included studies.·CONCLUSION：This Meta-analysis indicates that MLP with IVTA pretreatment has a better therapeutic effect in terms of CMT reduction and earlier（1mo）visual improvement for patients with DME as compared with MLP alone.Further confirmation with rigorously welldesigned multi-center trials is needed.

Macular edema after cataract surgery in diabetic eyes evaluated by optical coherence tomography

AIM：To assess quantitative changes of the macula in diabetic eyes after cataract surgery using optical coherence tomography（OCT）and to estimate the incidence of development or worsening of macular edema（ME）in diabetic eyes with or without pre-existing ME.·METHODS：In this prospective,observational study,92eyes of 60 diabetic patients who underwent cataract surgery were evaluated before surgery and 1,3mo after surgery using OCT.Macular thickness was measured with OCT at nine macular subfields defined by the 9zones early treatment of diabetic retinopathy study（ETDRS）,as well as total macular volume obtained by OCT at 1,3mo after surgery were compared with baseline features obtained before surgery.In addition,the incidence of development or worsening of ME was analyzed in diabetic eyes with or without pre-existing ME.·R ESULTS：The central subfield mean thickness increased 21.0μm and 25.5μm at 1,3mo follow-up,respectively（〈0.01）.The average thickness of inner ring and outer ring increased 14.2μm and 9.5μm at 1mo,18.2μm and 12.9μm at 3mo.Central-involved ME developed in 12 eyes at 3mo,including 4 eyes with preexisting central-involved and 8 eyes with pre-existing non-central involved ME.Pre-existing diabetic macular edema（DME）was significantly associated with centralinvolved ME development（〈0.001）.·C ONCLUSION：A statistically significant increase could be detected in the central subfield as well as perifoveal and parafoveal sectors though the increase was mild.And eyes with pre-operative DME prior to cataract surgery are at higher risk for developing central-involved ME.

Current status in diabetic macular edema treatments

Diabetes is a serious chronic condition,which increase the risk of cardiovascular diseases,kidney failure and nerve damage leading to amputation.Furthermore the ocular complications include diabetic macular edema,is the leading cause of blindness among adults in the industrialized countries.Today,blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy.The treatment should include an optimized control of glycemia,arterial tension,lipids and renal status.The photocoagulation laser is currently restricted to focal macular edema in some countries,but due the high cost of intravitreal drugs,the use of laser treatment for focal and diffuse diabetic macular edema(DME),can be valid as gold standard in many countries.The intravitreal anti vascular endothelial growth factor drugs(ranibizumab and bevacizumab),are indicated in the treatment of all types of DME,but the correct protocol for administration should be defined for the different Retina Scientific Societies.The corticosteroids for diffuse DME,has a place in pseudophakic patients,but its complications restricted the use of these drugs for some patients.Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.