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.

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.

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.

Optical Coherence Tomography (OCT) Feature Identifying Niche for Dexamethasone (FIND) Intravitreal Implant in the Treatment of Anti-VEGF Slow Responders with Diabetic Macular Edema

This paper raises the question if intravitreal dexamethasone implant deserves to be utilized more effectively in a select subset of eyes with diabetic macular edema (DME). If so, what is the OCT morphology of such eyes? A retrospective consecutive case series is employed to answer these questions. Twenty consecutive eyes were studied: ten that have been treated with intravitreal anti-VEGF (Group A) injections and ten which have been treated with the steroidal implant (Group O) because they failed or were slow to respond to multiple injections of anti-VEGF medications. Specifically, 1) macular edema in the eyes were categorized for the type of OCT morphology and 2) their response to the respective treatments in terms of the resolution of the OCT morphology was determined. Results show that the OCT morphology of eyes that were in Group O predominantly (7/10) had the feature of posterior retinal leakage (subretinal fluid and large outer retinal cysts);this feature was rare in Group A (2/10). Further, each of these eyes (7/7) in Group O had a complete resolution of the macular edema after a single treatment with the dexamethasone intravitreal implant whereas neither eye with this feature (0/2) responded to the (anti-VEGF) treatment in Group A. This leads to the conclusion that there exists an OCT Feature that Identifies a Niche for Dexamethasone Intravitreal implant (FIND) in the treatment of anti-VEGF slow responders in DME. The clinical significance of the study is that selecting eyes with a priori FIND morphology on the OCT for treatment with dexamethasone implant prior to, or at the outset of, a series of anti-VEGF treatment may resolve DME promptly and lower the treatment burden for patients and cost to society.

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.

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.

Diabetic macular edema:Current management 2013

Diabetic retinopathy(DR)is the leading cause of vision loss of working-age adults,and diabetic macular edema(DME)is the most frequent cause of vision loss related to diabetes.The Wisconsin Epidemiologic Study of Diabetic Retinopathy found the 14-year incidence of DME in type 1 diabetics to be 26%.Similarly the Diabetes Control and Complications Trial reported that 27% of type 1 diabetic patients develop DME within9 years of onset.The most common type of diabetes,type 2,is strongly associated with obesity and a sedentary lifestyle.An even higher incidence of macular edema has been reported in older patients with type 2diabetes.Within the last 5 years,the use of intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor(VEGF)agents have come into clinical practice for the management of DME and several recent randomized clinical trials have shown improved effectiveness of ranibizumab compared to focal/grid laser.In this theme issue,we discuss the classification of DR and the treatment options currently available for the treatment of DME including corticosteroids,anti-VEGF agents,combined therapy,enzymatic vitrectomy(vitreolysis),and new therapies.

Real-world outcomes of two-year Conbercept therapy for diabetic macular edema

AIM: To evaluate the two-year outcomes of patients treated for diabetic macular edema(DME) with intravitreal Conbercept(IVC).METHODS: The clinical data of 30 DME patients(36 eyes) were retrospectively reviewed. The patients were treated with IVC for 3 mo. Additional IVC was given at subsequent monthly visits, if needed(3+PRN). The patients were followed up for 24 mo.RESULTS: The best-corrected visual acuity(BCVA) at 24 mo significantly increased(66.7±15.3 letters) in comparison with the baseline(54.4±15.4 letters, P<0.0001). The mean improvement in BCVA was 11.0±2.9 letters. At 24 mo, 44.1% of the eyes surveyed gained ≥15 letters, 52.9% of the eyes gained ≥10 letters, and 70.6% of the eyes gained ≥5 letters. No vision loss was noted in 96.8% of the eyes, and 5.9% of the eyes lost ≥5 letters, but ≤10 letters. The central retinal thickness(CRT) at 24 mo was significantly reduced(277.1±122.9 μm) in comparison with the baseline(510.9±186.1 μm, P<0.0001). At 24 mo, 43.3% of the patients had a CRT ≤250 μm. The mean number of injections over 24 mo was 10.6±2.0. No severe eye or systemic adverse events related to either the drug or injection were noted.CONCLUSION: IVC is safe and effective for the treatment of DME.

Intravitreal triamcinolone versus intravitreal bevacizumab for diabetic macular edema:a meta-analysis

AIMTo compare the efficacy of the sole intravitreal triamcinolone (IVT) versus intravitreal bevacizumab (IVB) alone or IVB combined with IVT in the treatment of diabetic macular edema (DME).

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.

Malfunction of outer retinal barrier and choroid in the occurrence and progression of diabetic macular edema

Diabetic macular edema(DME) is the most common cause of vision loss in diabetic retinopathy,affecting 1 in 15 patients with diabetes mellitus(DM).The disruption of the inner blood-retina barrier(BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris,in the occurrence and evolution of DME.The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition.In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.

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.

Comparison of intravitreal bevacizumab and triamcinolone acetonide theraphies for diffuse diabetic macular edema

AIM: To compare therapeutic effects of intravitreal triamcinolone acetonide(IVTA) versus intravitreal bevacizumab(IVB) injections for bilateral diffuse diabetic macular edema(DDME). METHODS: Forty eyes of 20 patients with bilateral DDME participated in this study. For each patient, 4 mg/0.1 m L IVTA was injected to one eye and 2.5 mg/0.1 m L IVB was injected to the other eye. The effects of injection for diabetic macular edema(DME) were evaluated using best-corrected visual acuity(BCVA), central macular thickness(CMT) by optical coherence tomography(OCT)and intraocular pressure(IOP) by applanation tonometer.Patients underwent eye examinations, including BCVA,CMT, and IOP at pre-injection, 1, 4, 8, 12 and 24 wk after injection. During the follow-up, second injections were performed to eyes which have CMT greater than 400 μm at 12 wk for salvage therapy.RESULTS: BCVA(logarithm of the minimum angle of resolution) at pre-injection, 1, 4, 8, 12 and 24 wk after injection was 0.71 ±0.19, 0.62 ±0.23, 0.63 ±0.12, 0.63 ±0.13,0.63±0.14 and 0.61±0.24 in the IVTA group and 0.68±0.25,0.61 ±0.22, 0.60 ±0.24, 0.62 ±0.25, 0.65 ±0.26 and 0.59 ±0.25 in the IVB group, respectively. CMT(μm) at pre-injection,1, 4, 8, 12 and 24 wk after injection was 544 ±125, 383±96,335 ±87, 323 ±87, 333 ±92, 335 ±61 in the IVTA group and514 ±100, 431 ±86, 428 ±107, 442 ±106, 478 ±112, 430 ±88 in the IVB group respectively. Reduction ratios of mean CMT were 29% at 1wk, 38% at 4wk, 40% at 8wk, 38% at12 wk, and 38% at 24 wk in the IVTA group. Second IVTA injections were performed to the 6 eyes(30%) at 12 wk.Reduction ratios of mean CMT were 16% at 1wk, 17% at4wk, 14% at 8wk, 7% at 12 wk, and 16% at 24 wk in the IVB group. Second IVB injections were performed to the15 eyes(75%) at 12 wk.CONCLUSION: This study showed earlier and more frequent macular edema recurrences in the eyes treated with bevacizumab compared with the ones treated with triamcinolone acetonide. Triamcinolone acetonide was found to provide more efficient and long-standing effect in terms of reducing CMT compared with the bevacizumab.

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.

Efficacy and mechanism of anti-vascular endothelial growth factor drugs for diabetic macular edema patients

BACKGROUND Diabetes is a serious public health concern in China,with 30%of patients developing retinopathy,and diabetic macular edema(DME)having the biggest impact on vision.High blood glucose level can cause retinal cell hypoxia,thus promoting vascular endothelial growth factor(VEGF)formation and increasing vascular permeability,which induces DME.Moreover,cell hypoxia can accelerate the rate of apoptosis,which leads to the aging of patients.In severe cases,optic cell apoptosis or retinal fibrosis and permanent blindness may occur.AIM To investigate and compare the efficacy,mechanism,and differences between two anti-VEGF drugs(Compaq and ranibizumab)in DME patients.METHODS Ninety-six patients with DME who attended our hospital from April 2018 to February 2020 were included and randomly divided into two groups(Compaq group and ranibizumab group).The groups received vitreal cavity injections of 0.5 mg Compaq and 0.5 mg ranibizumab,respectively,once a month.The best corrected visual acuity(BCVA),intraocular pressure(IOP),macular retinal thickness(CMT),macular choroidal thickness(SFCT),foveal no perfusion area(FAZ),superficial capillary density,deep capillary density,treatment effect,and adverse reactions were compared before and after treatment and between the two groups.RESULTS Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated BCVA in both groups(P>0.05).BCVA decreased in the Compaq group 3 mo after treatment,and the difference was statistically significant(P<0.05).Before treatment,and 1 mo and 3 mo post-treatment,there was no statistically significant difference in the estimated IOP in either group(P>0.05).Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated CMT,SFCT,or FAZ in either group(P>0.05).CMT and SFCT values decreased in the Compaq group 3 mo post-treatment,and the difference was statistically significant(P<0.05).Before treatment,and 1 mo and 3 mo post-treatment,there were no statistically significant differences in vascular density in the shallow or deep capillary plexi of the fovea,parafovea,or overall macular area between the two groups(P>0.05).Marked efficient,effective,and invalid rates were 70.83%and 52.08%,27.08%and 39.58%,and 2.08%and 8.33%in the Compaq and ranibizumab groups,respectively.The differences between the two groups were statistically significant(P<0.05).CONCLUSION Anti-VEGF drugs can effectively improve CMT and SFCT,without affecting microcirculation,thus providing an effective and safe treatment for patients with DME.