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.

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.

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.

Prevalence of and risk factors for diabetic macular edema in a northeastern Chinese population

AIM:To estimate the prevalence of diabetic macular edema(DME) and clinically significant macular edema(CSME),and to assess their risk factors in a population with type 2 diabetic mellitus(T2DM) located in northeast China.METHODS:Patients were included from the Fushun Diabetic Retinopathy Cohort Study(FS-DIRECT),a community-based study conducted in northeast China.The presence of DME and CSME was determined by the Early Treatment Diabetic Retinopathy Study(ETDRS) retinopathy scale of fundus photographs.The age-standardized prevalence of DME and CSME was estimated.The association between DME/CSME and risk factors was analyzed in a multivariate Logistical analysis.RESULTS:A total of 292(15.4%) and 166(8.8%) patients were diagnosed as DME and CSME,yielding the age and sex standardized prevalence of 13.5%(95%CI:11.9%-15.0%),and 7.1%(95%CI:5.9%-8.3%),respectively.Female patients had a higher prevalence of DME compared to their male counterparts(15.7% vs 10.4%,P=0.03).Multivariable Logistic regression analysis showed that younger age,insulin use,proteinuria,longer duration of diabetes,and higher glycosylated hemoglobin A1c,were associated with the prevalence of DME and CSME.Patients with higher fasting plasma glucose,systolic blood pressure,and blood urea nitrogen were also found to be associated with DME.CONCLUSION:Early fundus screening in diabetic patients is invaluable and given the relatively high prevalence of DME and CSME in this study cohort,those with a high risk of sight threatening maculopathy would invariably benefit from earlier detection.

Evaluation of systemic risk factors in different optical coherence tomographic patterns of diabetic macular edema

AIM： To elucidate the relationship between systemic risk factors and different patterns of diabetic macular edema（DME） determined with optical coherence tomography（OCT）. METHODS： In this cross-sectional study, DME was classified by OCT as diffuse retinal thickness（DRT）, cystoid macular edema（CME） and serous retinal detachment（SRD） and the relationship between the systemic risk factors and DME patterns was evaluated. RESULTS： Of the 57 patients with DME, 21（36.8%） had DRT, 24（42.1%） had CME and 12（21.0%） had SRD. Microor macro-albuminuria was significantly higher in the DRT pattern（61.9%） compared with the SRD（50.0%） and CME patterns（25.0%; P=0.040）. Hemoglobin A1 c（Hb A1 c） level was significantly higher and patients were younger in the DRT pattern group（P=0.034, P=0.032）. Best corrected visual acuity was the worst and central macular thickness was the thickest in the CME pattern group. CONCLUSION： Micro-or macro-albuminuria may be more frequent and Hb A1 c level may be higher in patients with DRT. These patients are also seen to be younger than patients with non-DRT.

Prognostic factors of short-term outcomes of intravitreal ranibizumab in diabetic macular edema

AIM：To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab（IVR） for diabetic macular edema（DME）.METHODS：Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity（BCVA） between 20/400 and 20/40. BCVA and central subfield thickness（CST） at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month 3.RESULTS：Younger age, poorer baseline BCVA and proliferative diabetic retinopathy（PDR） were correlated with better visual improvement at month 3（P=0.002, 0.0001 and 0.007, respectively）. Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST（P〈0.0001 and P=0.018, respectively）. The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide（PSTA） were associated with a smaller reduction in CST（P=0.029 and 0.018, respectively）, but had no significant effects in visual improvement at month 3（P〉0.05 for both）.CONCLUSION：For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema

Diabetic macular edema(DME)is a very important and well-known cause of visual loss in diabetics.Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME.Even though it is not clearly understood,current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME.Clinical trials are continuously shaping our treatment approaches for the eyes with DME.Today,vascular endothelial growth factor(VEGF)inhibitor and steroid administrations are the main alternatives in DME treatment.Dexamethasone(DEX)implant(Ozurdex®;Allergan,Inc.,Irvine,CA,United States)was approved by the United States Food&Drug Administration in 2014 for DME treatment.The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time.Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile.DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents.Thus,DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy.However,it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes.Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event,pregnancy and noncompliant to frequent visits.This mini-review briefly overviews the efficacy,safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.

Optical coherence tomography angiography assessment of 577 nm laser effect on severe non-proliferative diabetic retinopathy with diabetic macular edema

AIM:To quantitatively evaluate the effect of the combined use of 577-nm subthreshold micropulse macular laser(SML)and multi-point mode pan retinal laser photocoagulation(PRP)on severe non-proliferative diabetic retinopathy(NPDR)with central-involved diabetic macular edema(CIDME)using optical coherence tomography angiography(OCTA).METHODS:In this observational clinical study,86 eyes of 86 NPDR patients with CIDME who underwent SML and PRP treatment were included.Images were obtained 1 d before laser and post-laser(1 d,1 wk,1,3,and 6 mo)using AngioV ue software 2.0.Best corrected visual acuity(BCVA,LogM AR),foveal avascular zone area(FAZ),choriocapillary flow area(Ch F),parafoveal vessel density(PVD),capillary density inside disc(CDD),peripapillary capillary density(PCD),macular ganglion cell complex thickness(m GCCT),central macular thickness(CMT),and subfoveal choroidal thickness(ChT)were compared between pre-and post-laser treatment.RESULTS:BCVA remained stable during 6 mo postlaser therapy(pre-laser vs 6 mo post-laser:0.53±0.21 vs 0.5±0.15,P>0.05).PVD,ChF,ChT,CMT,and mGCCT significantly increased 1 d post-laser therapy[pre-laser vs 1 d post-laser:superficial PVD(%),40.51±3.42 vs 42.43±4.68;deep PVD(%),42.66±3.67 vs 44.78±4.52;ChF,1.72±0.21 vs 1.9±0.12 mm^2;ChT,302.45±69.74 vs 319.38±70.93μm;CMT,301.65±110.78 vs 320.86±105.62μm;m GCCT,105.71±10.72 vs 115.46±9.64μm;P<0.05].However,PVD,ChF and ChT decreased to less than baseline level at 6 mo postlaser therapy(pre-laser vs 6 mo post-laser:superficial PVD(%),40.51±3.42 vs 36.32±4.19;deep PVD(%),42.66±3.67 vs 38.76±3.74;Ch F,1.72±0.21 vs 1.62±0.09 mm^2;Ch T,302.45±69.74 vs 289.61±67.55μm;P<0.05),whereas CMT and mG CCT decreased to baseline level at 6 mo postlaser therapy(CMT,301.65±110.78 vs 297.77±90.23μm;m GCCT,105.71±10.72 vs 107.05±11.81μm;P>0.05).Moreover,FAZ continuously increased while CDD and PCD continuously decreased in 6 mo after laser therapy.CMT and ChT had a significant positive correlation with ChF and PVD in most post-laser stages.CONCLUSION:During a 6-month follow-up period after combined use of SML and PRP therapy,BCVA remained stable and there was a decreased trend in macular edema.Blood flow increased at 1 d post-laser therapy and reduced at 6 mo post-laser therapy.

Aqueous angiopoietin-like levels correlate with optical coherence tomography angiography metrics in diabetic macular edema

AIM:To quantitatively detect aqueous levels of angiopoietin-like(ANGPTL)3,ANGPTL4,and ANGPTL6 and investigate their correlation with optical coherence tomography angiography(OCTA)findings in patients with diabetic macular edema(DME).METHODS:This cross-sectional study included 23 patients(27 eyes)with type 2 diabetes and 16 control subjects(20 eyes).All patients underwent OCTA imaging and ultra-wide field fundus photography.Diabetic patients were categorized into two groups according to the presence or absence of diabetic retinopathy(DME group,14 patients,16 eyes);and non-diabetic retinopathy(NDR)group,9 patients,11 eyes,respectively.Aqueous levels of ANGPTL3,ANGPTL4,and ANGPTL6 were assessed using suspension array technology,and foveal-centered 3×3 mm2 OCTA scans were automatically graded to determine the central,inner,and full vessel density(CVD,IVD,FVD);central,inner,and full perfusion density(CPD,IPD,FPD),foveal avascular zone(FAZ)area,FAZ perimeter,and FAZ circularity index(FAZ-CI)on superficial capillary plexuses.Additionally,central subfield thickness(CST),cube volume(CV),and cube average thickness(CAT)were measured in a model of macular cube 512×128.RESULTS:Aqueous ANGPTL3 levels were not significantly different among the three groups(P>0.05).ANGPTL4 levels were significantly higher in the DME group than the control and NDR groups(P<0.0001 and P<0.001),while ANGPTL6 levels were significantly higher in the DME group than the control group(P<0.05).In the whole cohort,the aqueous ANGPTL3 levels correlated negatively with the IVD,FVD,IPD,and FPD,and positively with the CV and CAT.The aqueous ANGPTL4 levels correlated negatively with the CVD,IVD,FVD,CPD,IPD,and FPD,and positively with the FAZ perimeter,CST,CV,and CAT.The aqueous ANGPTL6 levels correlated negatively with the IVD,FVD,IPD,FPD,FAZCI and positively with CST,CV,CAT.CONCLUSION:ANGPTL4 and ANGPTL6 may be associated with vascular leakage in DME and may represent good targets for DME therapy.In addition,OCTA metrics may be useful for evaluating macular ischemia in DME.

Three-dimensional diabetic macular edema thickness maps based on fluid segmentation and fovea detection using deep learning

AIM: To explore a more accurate quantifying diagnosis method of diabetic macular edema(DME) by displaying detailed 3D morphometry beyond the gold-standard quantification indicator-central retinal thickness(CRT) and apply it in follow-up of DME patients.METHODS: Optical coherence tomography(OCT) scans of 229 eyes from 160 patients were collected.We manually annotated cystoid macular edema(CME), subretinal fluid(SRF) and fovea as ground truths.Deep convolution neural networks(DCNNs) were constructed including U-Net, sASPP, HRNetV2-W48, and HRNetV2-W48+Object-Contextual Representation(OCR) for fluid(CME+SRF) segmentation and fovea detection respectively, based on which the thickness maps of CME, SRF and retina were generated and divided by Early Treatment Diabetic Retinopathy Study(ETDRS) grid.RESULTS: In fluid segmentation, with the best DCNN constructed and loss function, the dice similarity coefficients(DSC) of segmentation reached 0.78(CME), 0.82(SRF), and 0.95(retina).In fovea detection, the average deviation between the predicted fovea and the ground truth reached 145.7±117.8 μm.The generated macular edema thickness maps are able to discover center-involved DME by intuitive morphometry and fluid volume, which is ignored by the traditional definition of CRT>250 μm.Thickness maps could also help to discover fluid above or below the fovea center ignored or underestimated by a single OCT B-scan.CONCLUSION: Compared to the traditional unidimensional indicator-CRT, 3D macular edema thickness maps are able to display more intuitive morphometry and detailed statistics of DME, supporting more accurate diagnoses and follow-up of DME patients.

RETRACTED:Exploring the Mechanism of Wu Ling San plus Flavor for the Treatment of Diabetic Macular Edema Based on Network Pharmacology and Molecular Docking Techniques

Short Retraction Notice The paper does not meet the standards of “Chinese Medicine ". This article has been retracted to straighten the academic record. In making this decision the Editorial Board follows COPE's Retraction Guidelines. The aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. Editor guiding this retraction: Prof. Maythem Saeed (EiC of CM) The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED".

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 integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema

AIM： To respectively evaluate macular morphological features and functional parameters by using spectraldomain optical coherence tomography（SD-OCT） and macular integrity assessment（MAIA） in patients with diabetic macular edema（DME）. METHODS： This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity（BCVA） measurement, MAIA microperimetry, and SDOCT. DME morphology, including central retinal thickness（CRT） and central retinal volume（CRV）; integrity of the external limiting membrane（ELM） and photoreceptor inner segment/outer segment（IS/OS） junction; and the deposition of hard macular exudates were assessed within a 1000-μm central subfield area. MAIA microperimetry parameters evaluated were average threshold（AT）-retinal sensitivity, macular integrity index（MI）, fixation points within a circle of radius 1°（P1） and 2°（P2）, and bivariate contour ellipse area considering 63% and 95% of the fixation points（A63 and A95, respectively）. RESULTS： MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA（log MAR）, total AT, AT within 1000-μm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA（log MAR）, AT within 1000-μm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION： Functional（BCVA and visual field） and morphological parameters（retinal thickness） were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.