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.

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.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion

AIM:To evaluate the efficacy,timing of retreatment and safety of dexamethasone(DEX)implant on macular edema(ME)secondary to diabetic retinopathy(DME)and retinal vein occlusion(RVO-ME)patients who were refractory to anti-vascular endothelial growth factor(VEGF)treatment.METHODS:This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1,2019,and January 1,2023.These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness(CRT).The best corrected visual acuity(BCVA)and CRT were measured at baseline,and at 1,3,4 and 6mo post-DEX implant injection.Adverse events such as elevated intraocular pressure(IOP)and cataract were recorded.RESULTS:For RVO cases(n=22),there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection(P<0.05)and CRT decreased from 472.1±90.6 to 240.5±39.0μm at 6mo(P<0.0001).DME cases(n=15)experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection(P=0.0098),with CRT reducing from 445.7±55.7 to 271.7±34.1μm at 6mo(P<0.0001).Elevated IOP occurred in 45.9%of patients but was well-controlled with topical medications.No cases of cataract or other adverse events were reported.CONCLUSION:DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME.Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

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).

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.

Dexamethasone implant in naive versus refractory patients with diabetic macular edema:a Meta-analysis

AIM:To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema(DME).METHODS:PubMed,Embase,Web of Science,and Medline databases were searched.The main outcomes were best-corrected visual acuity(BCVA)and central retinal thickness(CRT).The secondary outcomes included mean number of injections,intraoperative or postoperative complications including intraocular pressure(IOP)elevation and cataract.RESULTS:Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected.The postoperative BCVA in the naive group was significantly better than in the refractory group[mean difference(MD)-0.11,95%confidence interval(CI)-0.17 to-0.05,P=0.0003;MD 8.69,95%CI 5.08 to 12.30,P<0.00001].Additionally,the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group[MD 7.71,95%CI 2.02 to 13.40,P=0.008;odds ratio(OR)2.99,95%CI 2.05 to 4.37,P<0.00001].The subgroup analysis revealed that the naive group had significantly higher BCVA gains of≥5,≥10,and≥15 letters compared to the refractory group(P=0.002,0.0001,0.003,respectively).No significant difference was detected between the two groups in either postoperative CRT(MD-22.36,95%CI-46.39 to 1.66,P=0.07)or the overall mean number of injections(MD-0.08,95%CI-0.38 to 0.22,P=0.61).Intraoperative and postoperative complications including the elevation of IOP(OR 0.47,95%CI 0.20 to 1.13,P=0.09)and cataract(OR 1.78,95%CI 0.97 to 3.24,P=0.06)showed no significant differences between the two groups during the follow-up time.CONCLUSION:Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety profile.Moreover,naive eyes maintain better visual outcomes than refractory eyes.It provides further evidence of better visual response when used for naive eyes as firstline therapy.

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.

Effects of vitrectomy combined with internal limiting membrane peeling in patients with diabetic macular edema

BACKGROUND Diabetic macular edema(DME),a chronic microvascular complication of diabetes,is a leading cause of visual impairment and blindness.Pars plana vitrectomy(PPV)can restore the normal macular structure and reduce macular edema,whereas internal limiting membrane(ILM)peeling is used to treat tractional macular diseases.Despite the advantages,there is limited research on the combined effects of PPV with ILM peeling.AIM To observe the effects of PPV combined with ILM peeling on postoperative central macular thickness(CMT),best-corrected visual acuity(BCVA),cystoid macular edema(CME)volume,and complications in patients with DME.METHODS Eighty-one patients(92 eyes)diagnosed with DME at the Beijing Shanqu Liangxiang Hospital between January and December 2022 were randomly divided to undergo PPV alone(control group:41 patients,47 eyes)or PPV+ILM peeling(stripping group:40 patients,45 eyes);a single surgeon performed all surgeries.The two groups were compared preoperatively and 1 and 3 months postoperatively.RESULTS Preoperatively,both groups had comparable values of CMT,BCVA,and CME volume(P>0.05).After surgery(both 1 and 3 months),both groups showed significant reductions in CMT,BCVA,and CME volume compared to preoperative levels,with the stripping group showing more significant reductions compared to the control group(P<0.05).Further repeated-measures ANOVA analysis for within-group differences revealed significant effects of group and time,and interaction effects for CMT,BCVA,and CME volume(P<0.05).There were no significant differences in the incidence of complications between the groups(retinal detachment:control=2,stripping=1;endophthalmitis:Control=4,stripping=1;no cases of secondary glaucoma or macular holes;χ^(2)=0.296,P=0.587).CONCLUSION PPV with ILM peeling can significantly improve the visual acuity of patients with DME,reduce CMT,and improve CME with fewer complications.

Comparison of efficacy of conbercept,aflibercept,and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion:a Meta-analysis

AIM:To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor(VEGF)drugs in the treatment of macular edema(ME)due to retinal vein occlusion(RVO)based on the evidence pooled from current clinical trials and observational studies.METHODS:A systematic literature search was conducted on nine online databases from inception until April 30,2022.The main endpoints were best corrected visual acuity(BCVA),central macular thickness(CMT),and adverse events(AEs).Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs.The retrieved data were analyzed using Stata software(version 12.0).RESULTS:A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis.It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo[weight mean difference(WMD)=-0.03,P=0.001;WMD=-0.05,P=0.019],but the effects were not different from that of ranibizumab at 6mo.Moreover,there was not statistically significant dif ference in the propor tion of patients gaining≥15 letters at 12-24mo between aflibercept and ranibizumab[odds ratio(OR)=1.16,P=0.427].Conbercept had higher mean CMT change effects at 1mo(WMD=-14.43,P=0.014)and 6mo(WMD=-35.63,P≤0.001)compared with ranibizumab.Meanwhile,the mean CMT change effects at 1mo(WMD=-10.14,P=0.170),6mo(WMD=-26.98,P=0.140)and 12-24mo(WMD=-12.34,P=0.071)were comparable among the groups.Similarly,AEs were not significantly different among the treatments(OR=0.75,P=0.305;OR=1.04,P=0.89).The stability of effect size of mean BCVA and CMT improved with the increase in sample size.Aflibercept and conbercept required fewer injections compared with ranibizumab.CONCLUSION:This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept,ranibizumab,and aflibercept in the treatment of RVOME.Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab.Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

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.

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.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.

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.

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.

Real-World Study on the Treatment of Macular Edema in Central Retinal Vein Occlusion Using Traditional Chinese Medicine(TCM)and Its Medication Guidelines

Object:The aim is to evaluate how effective Traditional Chinese Medicine(TCM)is in treating patients who have central retinal vein occlusion with macular edema(CRVO-ME)in a real-world study.Furthermore,the objective of the research was to examine the TCM prescription trends in the management of CRVO-ME.Method:A single-center real-world study(RWS)was carried out over a span of 19 years,following the established design.The study encompassed 113 patients diagnosed with CRVO-ME.Out of these,74 patients received TCM treatment,while the remaining individuals underwent a combined therapy involving TCM and anti-VEGF drugs through intravitreal injection.The patients were matched using propensity score matching(PSM).The result measured in the RWS was BCVA.The oral prescriptions for CRVO-ME that led to observable and effective outcomes were collected.Excel and the TCM Inheritance Auxiliary Platform V2.5 were utilized to optimize mutual information,hierarchical clustering based on entropy,and other techniques to extract medication regulations and features.Result:After applying PSM,each group comprised 29 cases.Both groups exhibited improved BCVA following treatment;however,there was no statistically significant distinction in BCVA or effectiveness between the two groups(all P>0.05).Apart from the analysis of oral prescriptions for CRVO-ME,the investigation pinpointed the most frequently used TCMs,namely Flos Carthami,Semen Persicae,Radix Angelica sinensis,Radix Rehmanniae,and Radix et Rhizoma Notoginseng.Frequently utilized medications tended to possess cold,warm,or mild attributes and exhibited a taste profile that was either bitter or sweet.The primary meridians associated with the medicines employed in treating CRVO-ME were liver,spleen,stomach,heart,and lung.Through the application of association rule analysis,it was discerned that there were 195 commonly employed combinations of medicines.Additionally,a complex system entropy cluster analysis unveiled 13 key combinations of medicines.By employing an unsupervised entropy hierarchical clustering analysis,a novel prescription was formulated.Conclusion:Within a real-world population of CRVO-ME patients,TCM exhibited its effectiveness.The treatment approach for CRVO-ME predominantly involved the regulation of qi(Qi is an exceedingly subtle substance within the human body,brimming with vitality and ceaseless motion.It constitutes the fundamental element that shapes and sustains the various processes of human life.)and blood as well as the resolution of dampness.The oral prescriptions frequently targeted the meridians of liver,spleen,stomach,heart,and lungs.

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.

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.

Importance of 3-D image reconstruction of spectraldomain OCT on outcome of grid laser photocoagulation for diffuse diabetic macular edema

AIM:To present the outcome of modified grid laser photocoagulation(GLP)in diffuse diabetic macular edema(DDME)in eyes without extrafoveal and/or vitreofoveal traction.METHODS:Inclusion criteria for the retrospective study were DDME eyes of patients with typeⅡdiabetes mellitus that had≥4 months of follow-up following GLP.Only one eye per patient was analyzed.Using 3-D spectral-domain optical coherence tomography(3-D SDOCT),eyes that had either extrafoveal or vitreofoveal traction,or had been previously treated by an intravitreal medication(s)were excluded.Treated DDME eyes were divided into 4 groups:A)"Classic"DDME that involved the central macula;B)edema did not involve the macular center;C)eyes associated with central epiretinal membrane(ERM);D)DDME that was associated with macular capillary dropout≥2 disc-diameter(DD).RESULTS:GLP outcome in 35 DDME eyes after 4-24(mean,13.1±6.9)months was as follows:Group A)18eyes with"classic"DDME.Following one or 2(mean,1.2)GLP treatments,best-corrected visual acuity(BCVA)improved by 1-2 Snellen lines in 44.4%(8/18)of eyes,and worsened by 1 line in 11.1%(2/18).Central macular thickness(CMT)improved by 7%-49%(mean,26.6%)in77.8%(14/18)of eyes.Causes of CMT worsening(n=4)were commonly explainable,predominantly(n=3)associated with emergence of extrafoveal traction,5-9months post-GLP.Group B)GLP(s)in DDME that did not involve the macular center(n=6)resulted in improved BCVA by 1-2 lines in 2 eyes.However,the central macula became involved in the edema process after the GLP in 3(50%)eyes,associated with an emergence of extrafoveal traction in one of these eyes 4months following the GLP.Group C)GLP failed in all 5eyes associated with central ERM.Group D)GLP was of partial benefit in 2 of 6 treated eyes with macular capillary dropout≥2DD.CONCLUSION:Eyes with DDME that involved the macular center were found to achieve favourable outcomes after GLP(s)during mid-term follow-up,unless complicated pre-GLP or post-GLP by vltreoretinal interface abnormalities,often extrafoveal traction or ERM,or by capillary dropout≥2DD.Prospective studies with larger cohorts are required.

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.