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).

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.

Is laser photocoagulation still effective in diabetic macular edema? Assessment with optical coherence tomography in Nepal

AIM: To find out the outcome of laser photocoagulation in clinically significant macular edema (CSME) by optical coherence tomography (OCT). · METHODS: It was a prospective, non-controlled, case series study enrolling 81 eyes of 64 patients with CSME between August 2008 and January 2010. All patients received modified grid photocoagulation with frequency doubled Nd: YAG laser. Each patient was evaluated in terms of best-corrected visual acuity (BCVA) and regression or progression of maculopathy after laser therapy at 1, 3 and 6 months. Spearman’s correlation test was used to show the correlation between BCVA and total macular volume (TMV). Analysis of variance (ANOVA) was used to compare among groups and independent t-test was used to compare in each group. · RESULTS: There is high correlation between BCVA and TMV (P ≤0.001). BCVA improved in 50.6%, remained static in 39.5 % and deteriorated in 9.9% patients after 6 month of treatment. The Baseline TMV (mean and SD) were 9.26±1.83, 10.4±2.38, 11.5±3.05, 8.89±0.75 and 9.47±1.98 mm3 for different OCT patterns, ST (sponge like thickening), CMO (cystoid macular edema), SFD (subfoveal detachment), VMIA (Vitreo macular interface abnormality) and average TMV respectively (P =0.04). After 6 months of laser treatment, the mean TMV decreased from 9.47±1.98mm3 to 8.77±1.31mm3(P =0.01). In ST there was significant decrease in TMV, P =0.01, Further within these groups at 6 months, they were significantly different, P =0.01. · CONCLUSION: OCT showed the different morphological variant of CSME while the response of treatment is different. TMV decreased the most and hence showed the improvement in vision after 6 months of laser treatment. In the era of Anti vascular endothelial growth factors (VEGFs), efficacy of laser seems to be in shadow but it is still first line of treatment in developing nation like Nepal where antiVEGFs may not be easily available and affordable.

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.

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.

Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation combination therapy for macular edema secondary to retinal vein occlusion: preliminary report

AIM： To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor （VEGF） agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema （ME） secondary to retinal vein occlusion （RVO）. METHODS： This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity （BCVA）, central retinal thickness （CRT）, and retinal vessel oxygenation were examined over 12mo. RESULTS： Patients received 1.43＋0.81 anti-VEGF injections. Mean baseline and 12-month IogMAR BCVA were 0.96±0.51 （20/178） and 0.31±0.88 （20/40）, respectively, in eyes with central retinal vein occlusion （CRVO） （P〈0.00）, and 1.02±0.45 （201209） and 0.60±0.49 （20/80）, respectively, in eyes with branch retinal vein occlusion （BRVO） （P〈0.00）. At 12mo, CRT had significantly decreased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. Venous oxygen saturation had significantly increased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION： Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO- associated ME.

Comparison of intravitreal bevacizumab with macular photocoagulation for treatment of diabetic macular edema: a systemic review and Meta-analysis

AIM: To further evaluate the efficacy and safety of intravitreal bevacizumab(IVB) versus macular photocoagulation(MPC) in treatment of diabetic macular edema(DME) by Meta-analysis. METHODS: Pertinent publications were identified through systemic searches of Pub Med, Medline,EMBASE, and the Cochrane Controlled Trials Register up to 30 November, 2013. Changes in central macular thickness(CMT) in μm and best-corrected visual acuity(BCVA) in log MAR equivalents were extracted at 1, 3, 6,12 and 24 mo after initial treatment, and a Meta-analysis was carried out to compare results between groups receiving IVB and MPC.RESULTS: Five randomized controlled trial(RCTs) and one high-quality comparative study were identified and included. Our Meta-analysis revealed that both IVB and MPC resulted in the improvements of CMT and BCVA in eyes with DME at 1mo after initial treatment, with IVB being significantly superior to MPC(P =0.01 and 0.02,respectively). The improvements of both measure outcomes at 3, 6, 12 and 24 mo after treatment did not vary significantly between the IVB groups and MPC groups(CMT at 3mo, P =0.85; at 6mo, P =0.29; at 12 mo,P =0.56; at 24 mo, P =0.71; BCVA at 3mo, P =0.31; at 6mo,P =0.30; at 12 mo, P =0.23; at 24 mo, P =0.52). However,the number of observed adverse events was low in all studies.CONCLUSION: Current evidence shows IVB treatment trends to be more effective in improvements of macular edema and vision in eyes with DME at an earlier follow up(1mo) compared with MPC. At other time, both interventions have comparable efficacy without statistical significances.

Clinical observation of vitrectomy combined with endolaser photocoagulation at the edge of posterior scleral staphyloma for macular hole retinal detachment in high myopia

AIM: To observe the clinical effect of pars plana vitrectomy(PPV) and silicone oil filling surgery combined with intraoperative posterior scleral staphyloma(PS) marginal retinal photocoagulation in the treatment of high myopic macular hole retinal detachment(MHRD) with PS.METHODS: This was a retrospective clinical study. From May 2017 to March 2020, 62 MHRD patients with PS(62 eyes) were enrolled in the study. Patients were divided into 23 G PPV combined with PS marginal retina intraoperative photocoagulation group(combined group) and conventional surgery group(conventional group), with 31 eyes in each. Triamcinolone acetonide and indocyanine green were used to remove the epiretinal membrane and the posterior macular inner limiting membrane(ILM). In the combined group, 2 to 3 rows of retinal photocoagulation were performed on the edge of the PS. The patients were followed up for an average of 8.34±3.21 mo. The first retinal reattachment rate, macular hole closure rate, Duration of silicone oil tamponade, best corrected visual acuity(BCVA) and average number of operations were observed and compared between the two groups.RESULTS: The first retinal reattachment rates of the eyes in the combined group and the conventional group were 96.7%(29/31) and 67.7%(21/31), respectively(χ~2=6.613, P=0.010). The macular hole closure rates in the combined group and the conventional group were 74.2%(23/31) and 67.7%(21/31), respectively(χ~2=0.128, P=0.721). The Duration of silicone oil tamponade of the patients in the combined group was lower than that of the routine group(t=-41.962, P≤0.001). Postoperative log MAR BCVA values of patients in the combined group and the conventional group were 1.27±0.12 and 1.26±0.11, compared with the log MAR BCVA before surgery, each group was improved(t=19.947, t=-19.517, P≤0.001, P≤0.001). There was no significant difference in the log MAR BCVA between the eyes of the two groups(t=-0.394, P=0.695). The average numbers of operations on the eyes in the conventional group and the combined group were 2.39±0.62 and 2.06±0.25 times, the combined group had fewer operations on average(t=-2.705, P=0.009). CONCLUSION: Intraoperative PPV treatment of MHRD with PS combined with PS marginal endolaser photocoagulation can effectively increase the rate of retinal reattachment after the first operation, reduce the number of repeated operations, and reduce the postoperative duration of silicone oil tamponade.

Short-term effects of intravitreal Conbercept injection combined with laser photocoagulation on macular edema secondary to ischemic retinal vein occlusion

AIM:To observe changes in the best-corrected visual acuity(BCVA),central macular thickness(CMT),and central choroidal thickness(CCT)of patients with macular edema(ME)secondary to ischemic retinal vein occlusion(i RVO)following intravitreal Conbercept injection.METHODS:This retrospective study included 33 eyes from 33 patients who received intravitreal injections of Conbercept for ME secondary to i RVO.Treatments were performed on a 3+pro re nata(3+PRN)basis.All of the patients were examined by fundus fluorescein angiography and spectral domain optical coherence tomography at the first visit.Laser photocoagulation was performed in the nonperfusion area of the retina of all eyes after the first injection.BCVA,CMT,and CCT were observed before and after 6 mo of treatment.The number of injections necessary to achieve improved vision was also noted.RESULTS:Following Conbercept treatment,the mean BCVA significantly improved from 0.81±0.39 at baseline to 0.41±0.25 and 0.43±0.29 log MAR in the third and sixth months,respectively(both P=0.000).The CMT of the patients at baseline was 556.75±98.57μm;304.78±68.53 and 306.85±76.77μm 3 and 6 mo after treatment,respectively(both P=0.000 vs baseline).The CCTs of the patients at baseline,3 and 6 mo after treatment were 304.63±57.83,271.31±45.53,and 272.29±39.93μm,respectively(P=0.026 and 0.035 vs baseline).No severe adverse event relevant to the therapy was noted,and the average number of injections delivered was 3.35.CONCLUSION:Intravitreal Conbercept injection combined with laser photocoagulation appears to be a safe and effective treatment for ME secondary to i RVO in the short-term.

Intravitreal Bevacizumab with Grid Photocoagulation for Recurrent Macular Edema Secondary to Retinal Vein Occlusion

Purpose: To assess the efficacy of intravitreal bevacizumab (IVB) combined with grid photocoagulation in the management of recurrent macular edema secondary to retinal vein occlusion (RVO). Methods: This is a prospective, non-randomized, interventional study. Thirty five eyes with branch retinal vein occlusion (BRVO) and 15 eyes with central retinal vein occlusion (CRVO) were treated with grid photocoagulation combined with IVB for recurrent macular edema. The visual acuity, central macular thickness and intraocular pressure were outcome measures. The mean duration of follow-up was 18.1 ± 3.6 months. Results: One month after treatment, 45 of the 50 eyes showed complete resolution of the cystoid space. Compared with initial values, final central macular thickness was reduced significantly in both BRVO and CRVO groups (P < 0.001), but improvement in VA was significant only for eyes with BRVO (P = 0.012). The total number of IVB was 1.8 ± 0.3 for eyes with either BRVO or CRVO. Conclusion: IVB combined with grid photocoagulation is an effective treatment for reducing recurrent macular edema associated with RVO.

Effects of intravitreal conbercept before panretinal photocoagulation on lipid exudates in diabetic macular documented by optical coherence tomography

AIM: To evaluate the effects of intravitreal conbercept(IVC) as adjunctive treatments before panretinal photocoagulation(PRP) to decrease hyperreflective dots(HRDs) in Chinese proliferative diabetic retinopathy(PDR) patients. METHODS: Fifty-nine enrolled patients were categorized into 2 groups: single dose IVC(0.5 mg/0.05 m L) 1 wk before PRP(Plus group) or PRP only(PRP group). Six months later, we measured the best corrected visual acuity(BCVA), central macula thickness(CMT) by optical coherence tomography and counted the number of HRDs in different retina layers. RESULTS: The average CMT significantly decreased in Plus group but increased in PRP group. The average BCVA in the Plus group was also significantly better than that in the PRP group. Total HRDs decreased in the Plus group but increased in PRP group significantly. IVC pre-treatment has beneficial effects on reducing HRDs forming in the inner retina layer while the PRP alone increased the HRDs in the outer retina layer. CONCLUSION: IVC is a promising adjunctive treatment to PRP in the treatment of PDR. Single dose IVC one week before PRP is suggested to improve retina blood-retina barrier, decrease lipid exudate and inhibit HRDs development in PDR.

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis

AIM： To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab（IVR） versus laser therapy in treatment of diabetic macular edema（DME）.METHODS： Pertinent publications were identified through comprehensive searches of Pub Med, EMBASE, Web of Science, Cochrane Library, and Clinical Trials.gov to identify randomized clinical trials（RCTs） comparing IVR＋laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences（WMD） of change from baseline in best corrected visual acuity（BCVA） and central retinal thickness（CRT） at 6, 12, or 24 mo after initial treatment, and the risk ratios（RR） for the proportions of patients with at least 10 letters of improvement or reduction at 12 mo. Data regarding major ocular and nonocular adverse events（AEs） were collected and analyzed. The Review Manager 5.3.5 was used.RESULTS： Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR＋laser significantly improved BCVA compared with laser at 6mo（WMD： 6.57; 95% CI： 4.37-8.77; P〈0.00001）, 12mo（WMD： 5.46; 95% CI： 4.35-6.58; P〈0.00001）, and 24mo（WMD： 3.42; 95% CI： 0.84-5.99; P=0.009） in patients with DME. IVR＋laser was superior to laser in reducing CRT at 12 mo from baseline with statistical significance（WMD：-63.46; 95% CI：-101.19 to-25.73; P=0.001）. The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR＋laser arms compared with laser（RR： 2.13; 95% CI： 1.77-2.57; P〈0.00001 and RR： 0.37; 95% CI： 0.22-0.62; P=0.0002, respectively）. As for AEs, the pooled results showed that a significantly higher proportion ofpatients suffering from conjunctival hemorrhage（study eye） and diabetic retinal edema（fellow eye） in IVR＋laser group compared to laser group（RR： 3.29; 95% CI： 1.53-7.09; P=0.002 and RR： 3.02; 95% CI： 1.24-7.32; P=0.01, respectively）. The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR＋laser and laser alone.CONCLUSION： The results of our analysis show that IVR＋laser has better availability in functional（improving BCVA） and anatomic（reducing CRT） outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR＋laser may get a higher risk of suffering from conjunctival hemorrhage（study eye） and diabetic retinal edema（fellow eye）.

Efficacy of intravitreal conbercept combined with panretinal photocoagulation for severe nonproliferative diabetic retinopathy without macular edema

AIM: To assess efficacy of intravitreal conbercept(IVC) injection in combination with panretinal photocoagulation(PRP) vs PRP alone in patients with severe nonproliferative diabetic retinopathy(SNPDR) without macular edema(ME).METHODS: Forty-eight patients with SNPDR without ME(56 eyes) were divided into the PRP group and IVC+PRP group(the pulse group) in this retrospective clinical study. Conbercept was intravitreally administered to patients in the pulse group 1 wk before treatment with PRP and followed up for 1, 3, and 6 mo. The best-corrected visual acuity(BCVA, log MAR), center foveal thickness(CFT), visual acuity(VA) improvement, and adverse reactions were compared between groups.RESULTS: In the PRP group, the BCVA reduced at 1 and 3 mo before improving at 6 mo. In the pulse group, baseline BCVA decreased continuously at 1 mo, increased at 3 and 6 mo. BCVA in the pulse group was better than that in the PRP group at 1, 3, and 6 mo. There was an increase in CFT in the PRP group during follow-up compared with baseline. In the pulse group, CFT was increased at 1 mo relative to baseline, steadily decreased to the baseline level at 3 and 6 mo. There was a more significant reduction in CFT in the pulse group during follow-up compared with the PRP group. The effective rates of VA in the PRP and the pulse groups were 81.48% and 100%, respectively. CONCLUSION: As PRP pretreatment, a single dose of IVC administration has beneficial effects for preventing PRPinduced foveal thickening and increasing VA in patients with SNPDR without ME.

Hydromassage of macular hole edges for large and persistent full-thickness macular holes

●AIM:To introduce the macular hole(MH)hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH.●METHODS:This retrospective observational case series comprised 16 consecutive patients(17 eyes)diagnosed with MH.Inclusion criteria involved a hole aperture diameter larger than 600μm or the presence of an unclosed MH larger than 600μm following the previous vitrectomy.Standard MH repair procedures were administered in all cases,involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle.A comprehensive assessment was conducted for each case before and after surgery,and optical coherence tomography(OCT)images were captured at every follow-up point.●RESULTS:The mean preoperative aperture diameter was 747±156μm(range 611-1180μm),with a mean base diameter of 1390±435μm(range 578-2220μm).Following surgery,all cases achieved complete anatomical closure of MH,with 13 cases(76.5%)exhibiting type 1 closure and 4 cases(23.5%)demonstrating type 2 closure.No significant differences were observed in the preoperative OCT variables between the two closure types.Eyes with type 1 closure showed a significantly improved visual acuity(0.70±0.10,range 0.50-0.80)compared to those with type 2 closure(0.90±0.12,range 0.80-1.00,P=0.014).●CONCLUSION:The MH hydromassage technique demonstrates promising results,achieving acceptable closure rates in cases of large or persistent MH.This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

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.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

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

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

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

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

HCSP-Net:A Novel Model of Age-Related Macular Degeneration Classification Based on Color Fundus Photography

Age-related macular degeneration(AMD)ranks third among the most common causes of blindness.As the most conventional and direct method for identifying AMD,color fundus photography has become prominent owing to its consistency,ease of use,and good quality in extensive clinical practice.In this study,a convolutional neural network(CSPDarknet53)was combined with a transformer to construct a new hybrid model,HCSP-Net.This hybrid model was employed to tri-classify color fundus photography into the normal macula(NM),dry macular degeneration(DMD),and wet macular degeneration(WMD)based on clinical classification manifestations,thus identifying and resolving AMD as early as possible with color fundus photography.To further enhance the performance of this model,grouped convolution was introduced in this study without significantly increasing the number of parameters.HCSP-Net was validated using an independent test set.The average precision of HCSPNet in the diagnosis of AMD was 99.2%,the recall rate was 98.2%,the F1-Score was 98.7%,the PPV(positive predictive value)was 99.2%,and the NPV(negative predictive value)was 99.6%.Moreover,a knowledge distillation approach was also adopted to develop a lightweight student network(SCSP-Net).The experimental results revealed a noteworthy enhancement in the accuracy of SCSP-Net,rising from 94%to 97%,while remarkably reducing the parameter count to a quarter of HCSP-Net.This attribute positions SCSP-Net as a highly suitable candidate for the deployment of resource-constrained devices,which may provide ophthalmologists with an efficient tool for diagnosing AMD.

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.