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 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.

Efficacy comparison of multipoint and single point scanning panretinal laser photocoagulation in non-proliferative diabetic retinopathy treatment

BACKGROUND Non-proliferative diabetic retinopathy(NPDR)poses a significant challenge in diabetes management due to its microvascular changes in the retina.Laser photocoagulation,a conventional therapy,aims to mitigate the risk of progressing to proliferative diabetic retinopathy(PDR).AIM To compare the efficacy and safety of multi-spot vs single-spot scanning panretinal laser photocoagulation in NPDR patients.METHODS Forty-nine NPDR patients(86 eyes)treated between September 2020 and July 2022 were included.They were randomly allocated into single-spot(n=23,40 eyes)and multi-spot(n=26,46 eyes)groups.Treatment outcomes,including bestcorrected visual acuity(BCVA),central macular thickness(CMT),and mean threshold sensitivity,were assessed at predetermined intervals over 12 months.Adverse reactions were also recorded.RESULTS Energy levels did not significantly differ between groups(P>0.05),but the multi-spot group exhibited lower energy density(P<0.05).BCVA and CMT improvements were noted in the multi-spot group at one-month posttreatment(P<0.05).Adverse reaction incidence was similar between groups(P>0.05).CONCLUSION While energy intensity and safety were comparable between modalities,multi-spot scanning demonstrated lower energy density and showed superior short-term improvements in BCVA and CMT for NPDR patients,with reduced laser-induced damage.

Retinal laser photocoagulation and intravitreal injection of anti-VEGF for hemorrhagic retinal arterial microaneurysm

AIM:To evaluate the efficacy of retinal laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF)for hemorrhagic retinal arterial macroaneurysm(RAM).METHODS:This was a retrospective clinical study.Patients with hemorrhagic RAM were divided into 4 groups defined by different treatments:a retinal laser photocoagulation therapy monotherapy group,an anti-VEGF intravitreal injection monotherapy group,a laser and anti-VEGF combination therapy group,and an observation group.Visual acuity(VA),central macular thickness(CMT),and retinal hemorrhage area(RHA)were collected.RESULTS:Forty-seven eyes of 47 patients were enrolled.VA improved and had a significant difference between baseline and final in each treatment group(logMAR;laser group:1.90±0.53 vs 1.05±0.63,P<0.001;anti-VEGF group:1.75±0.63 vs 1.12±0.54,P=0.009;combination group:1.76±0.38 vs 1.01±0.52,P<0.001);however,VA decreased and had no significant difference in observation group(1.63±0.51 vs 1.76±0.61,P=0.660).CMT decreased and had a significant difference between baseline and final in each group(laser group:815.16±310.83 vs 252.05±83.90μm,P<0.001;anti-VEGF group:725.00±290.79 vs 203.56±69.89μm,P=0.001;combination group:595.50±186.51 vs 253.13±55.06μm,P=0.001;observation group:758.88±195.65 vs 267.00±120.90μm,P=0.001).RHA were 28.99±28.15,25.94±11.58,19.64±8.97,and 27.45±13.76 mm^(2) in laser group,anti-VEGF group,combination group and observation group,respectively.RHA was statistically correlated with final VA(P=0.032)in the observation group.CONCLUSION:Both laser and anti-VEGF treatments are effective for hemorrhagic RAM.Combination therapy reduces the number of injections of anti-VEGF.RHA is a visual prognosis predictor in the natural history of hemorrhagic RAM.

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.

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.

Change in subfoveal choroidal thickness after argon laser panretinal photocoagulation

AIMTo evaluate changes in subfoveal choroidal thickness (SFCT) and macular thickness as measured by enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) after argon laser panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy.

Long-term effects of pattern scan laser pan-retinal photocoagulation on diabetic retinopathy in Chinese patients: a retrospective study

●AIM:To evaluate the long-term effects of pattern scan laser(PASCAL)pan-retinal photocoagulation(PRP)on diabetic retinopathy(DR)in Chinese patients.●METHODS:In this retrospective study,we evaluated clinical data of 29 patients(53 eyes)with severe non-proliferative DR(SNPDR)or proliferative DR(PDR)who received PRP and follow-up at our hospital from 2008 to 2013.Sixteen patients(29 eyes)received PASCAL PRP and 13 patients(24 eyes)received 100-ms conventional laser PRP.●RESULTS:After long-term follow-up(mean,min-max days:719.8,290-1666 for PASCAL PRP vs 743.5,240-1348 for conventional PRP,P=0.569),patients receiving PASCAL PRP required fewer photocoagulation sessions than the conventional PRP group(2.6±1.0 vs 3.9±0.9,P<0.01).Best corrected visual acuity(BCVA)was reduced slightly in PASCAL PRP group while reduced significantly in conventional PRP group.At last visit,24 eyes in the PASCAL group(88.9%)and 21 eyes in the conventional group(91.7%)were improved or stable.Two eyes in PASCAL PRP group(7.4%)and 3 eyes in the conventional PRP group(12.5%)developed vitreous hemorrhage or vitreous fibrovascular proliferation.●CONCLUSION:PASCAL PRP is as effective and may be more conducive to maintaining visual acuity with less treatment sessions for DR treatment compared to conventional laser PRP.

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.

Efficacy and safety of intravitreal ranibizumab with panretinal photocoagulation followed by trabeculectomy compared with Ahmed glaucoma valve implantation in neovascular glaucoma

AIM：To evaluate the efficacy and safety of intravitreal ranibizumab（IVR）with panretinal photocoagulation（PRP）followed by trabeculectomy compared with Ahmed glaucoma valve（AGV）implantation in neovascular glaucoma（NVG）.METHODS：This was a retrospective comparative study.We reviewed the cases of a total of 45 eyes from 45 NVG patients among which 23 eyes underwent AGV implantation and the other 22 underwent trabeculectomy. The causes of neovascular glaucoma included：diabetic retinopathy（25 eyes）,and retinal vein occlusion（20 eyes）.All patients received preoperative IVR combined with postoperative PRP. The mean best-corrected visual acuities（BCVA）were converted to the logarithms of the minimum angle of resolution（log MAR）for the statisitical analyses.Intraocular pressure（IOP）,the log MAR BCVA and surgical complications were evaluated before and after surgery.The follow-up period was 12 mo.RESULTS：A total of 39 cases showed complete regression of iris neovascularization at 7d after injection,and 6 cases showed a small amount of residual iris neovascularization. The success rates were 81.8% and 82.6% at 12 mo after trabeculectomy and AGV implantation,respectively. In the trabeculectomy group,the log MAR BCVA improved at the last follow-up in 14 eyes,remained stable in 6 eyes and decreased in 2 eyes. In 4 cases,slight hyphemas developed after trabeculectomy. A shallow anterior chamber developed in 2 cases and 2 vitreous hemorrhages. In the AGV group,the log MAR BCVA improved in 14 eyes,remained stable in 5 eyes and decreased in 4 eyes. Slight hyphemas developed in 3 cases,and a shallow anterior chamber in 3 cases. The mean postoperative IOP was significantly lower in both groups after surgery（F=545.468,P〈0.05）,and the mean postoperative log MAR BCVA was also significantly improved（F=10.964,P〈0.05）with no significant difference between two groups.CONCLUSION：It is safe and effective to treat NVG with this combined procedure,and we found similar results after IVR＋AGV implantation＋PRP and IVR＋trabeculectomy＋PRP in eyes with NVG.

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.

Simultaneous pars plana vitrectomy,panretinal photocoagulation,cryotherapy,and Ahmed valve implantation for neovascular glaucoma

AIM:To describe and evaluate the efficacy of Ahmed glaucoma valve implantation(AGV)combined with pars plana vitrectomy(PPV)in a single surgical act for the treatment of advanced neovascular glaucoma(NVG).METHODS:Retrospective observational case series included 51 eyes from 50 patients with severe NVG treated with PPV,AGV,and panretinal photocoagulation and/or cryotherapy in a single surgical act during a 13-year period(2005-2018).Preoperative,intraoperative and postoperative data at day 1 and months 1,3,6,21,and 24 were systematically collected.Definition of surgical success was stablished at IOP between 6 and 21 mm Hg with or without topical treatment.RESULTS:Main indications for surgery were NVG secondary to proliferative diabetic retinopathy(39.2%)and central retinal vein occlusion(37.3%).Mean(±SD)preoperative IOP was 42.0±11.2 mm Hg decreasing to 15.5±7.1 mm Hg at 12 mo and 15.8±9.1 mm Hg at 24 mo of follow up.Cumulative incidence of success of IOP control was 76.0%at first postoperative month,reaching 88.3%at 6 mo.Prevalence of successful IOP control at long term was 74.4%at 12 mo and 71.4%at 24 mo.Eye evisceration for unsuccessful NVG management was required in 1 case(2.0%).CONCLUSION:Combination of AGV implantation and PPV in a single act may be a suitable option for severe forms of NVG in a case-by-case basis for effective IOP control and a complete panretinal photocoagulation.

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.

Influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy

Objective: To explore the influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy. Methods: A total of 170 patients with early proliferative DR who were treated in the hospital between December 2014 and May 2017 were retrospectively analyzed and divided into the control group (n=107) who received retinal photocoagulation therapy alone and the probucol group (n=63) who received probucol-assisted retinal photocoagulation therapy. The differences in the contents of visual performance indexes as well as serum angiogenesis indexes, inflammatory mediators and oxidative stress indexes were compared between the two groups before treatment and after 6 weeks of treatment. Results: Before treatment, the differences in the levels of visual performance indexes as well as serum contents of angiogenesis indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups of patients. After 6 weeks of treatment, mean vision, 30 visual acuity and 30-60 visual acuity of probucol group were higher than those of control group;serum angiogenesis indexes HIF-1, VEGF and Ang-2 contents were lower than those of control group;serum inflammatory mediators ICAM-1, IL-2, IL-23 and TNF-α contents were lower than those of control group;serum oxidative stress index MDA content was lower than that of control group whereas TAC content was higher than that of control group. Conclusion: Probucol-assisted retinal photocoagulation therapy can effectively optimize the visual performance and promote the homeostasis recovery in patients with early proliferative diabetic retinopathy.

Clinical correlation between blood glucose control-related factors and postoperative fundus hemorrhage after pan-retinal photocoagulation for diabetic retinopathy

Objective: To discuss the clinical correlation between blood glucose control-related factors and postoperative fundus hemorrhage after pan-retinal photocoagulation (PRP) for diabetic retinopathy (DR). Method: From February 2013 to January 2017, 98 patients at 7 d after PRP for DR were recruited. Depending on postoperative fundus status, the patients were divided into normal fundus group (n=42), fundus hemorrhage group (n=30) and proliferative DR group (n=27). The baseline data and monitoring data of blood glucose and blood lipid were recorded. Dynamic glucose monitor system was used to detect indicators of blood glucose fluctuation, MAGE and MBG. Result: The three groups were compared in terms of systolic pressure, diastolic pressure, course of disease, gender, age and body mass index (BMI), and no significant differences were found. As compared with the normal fundus group, the fundus hemorrhage group and proliferative DR group had a significant increase in FPG, HbA1c, 2hPG, LDL-C and TC, but a decrease in HDL-C. MAGE and MBG for the fundus hemorrhage group were (4.89±1.42) and (7.82±1.42), respectively, which were higher than those of the normal fundus group, but no significantly different from those of the proliferative DR group. Linear correlation analysis was performed in 98 patients, and significant linear correlations existed between MAGE, MBG, FPG, HbA1c and LDL-C with fundus hemorrhage. Conclusion: Blood glucose control-related factors MAGE, MBG, FPG, HbA1c and LDL-C were important influence factors of fundus hemorrhage following PRP for DR. Appropriate countermeasures are needed to reduce the fluctuation of blood glucose level.

Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

AIM： To evaluate the effects of panretinal photocoagulation （PRP） compared with PRP plus intravitreal bevacizumab （IVB） in patients with high-risk proliferative diabetic retinopathy （PDR） according to the Early Treatment Diabetic Retinopathy Study criteria.METHODS： The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP （PRP group） or PRP plus intravitreal injection of 1.25 mg of bevacizumab （PRP-Plus group）. Patients underwent complete ophthalmic evaluation, including best corrected visual acuity （BCVA）, intraocular pressure （IOP）, and new vessel size in fluorescein angiography （FA） and optical coherence tomography for the assessment of central subfield macular thickness （CSMT） at baseline and at weeks 12 （±2）, 16 （±2）, 24 （±2） and 48 （±2）. Main outcome measures also included vitreous clear-up time and neovascularization on the disc （NVD） regression time. Adverse events associated with intravitreal injection were investigated.RESULTS： Thirty consecutive patients （n=36 eyes） completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations （NVs）, BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group （P〈0.05）. Patients received an average of 1.3 injections （range： 1-2）. Ten eyes （27.8%） underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage （VH）. No major adverse events were identified.CONCLUSION： The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.

Dan Huang Ming Mu Recipe Suppresses the Progression of Streptozotocin-induced Diabetic Retinopathy After Retinal Laser Photocoagulation in Brown Norway Rats via Down-regulating Vascular Endothelial Growth Factor and Up-regulating Pigment Epithelium-derived

Objective To analyze the effects of Dan Huang Ming Mu Recipe(DHMMR)(a pharmaceutical preparation from herbs and having the function of replenishing vital essence,removing heat,promoting blood circulation and excreting pathogenic water) on diabetic retinopathy(DR) after retinal laser photocoagulation through regulating the expression of vascular endothelial growth factor(VEGF) and pigment epithelium-derived factor(PEDF).Methods Forty male Brown Norway(BN) rats were randomly divided into blank group(group A,10 BN rats) and model group(30 BN rats).DR models were induced by 40 mg/kg streptozotocin(STZ) and the body weight and blood glucose of rats were monitored.After 12-week injection,fluorescein fundus angiography(FFA) and histopathological examination were detected to confirm the successful establishment of DR models.Subsequently,the right eyes of model group rats were conducted retinal laser photocoagulation with the left eyes having no retinal laser photocoagulation and rats of the model group were randomly divided into group B(the model control group),group C(the positive control group),and group D(the DHMMR group),with 10 rats in each group.Rats of the group A and the group B were given vehicle,and the group C were given calcium dobesilate suspension by gavage,and the group D were given DHMMR by gavage.After 4-week gavage,FFA was carried out to observe the fundus microvascular change.Then,the rats were sacrificed to do histopathological examinations and the serum levels of P-selectin,cAMP,cGMP,and the relative expression of the protein of VEGF and PEDF in retina were detected.Results After 12-week STZ injection,the blood glucose of the model group were pronouncedly higher than the blank group(P < 0.01).Fundus micro-hemangioma changes were observed in the rats of the model group through FFA,and the rats of the blank group did not see any changes.The pictures of HE staining showed that the retinal structure of the model group was more disordered than the blank group.After 4-week gavage,treatments with DHMMR showed dramatic reduction of serum levels of Pselectin,cAMP and cGMP compared with the group B(P < 0.01).FFA and histopathological examinations of DHMMR-treated rats revealed significantly suppression of retinal edema,fundus microvascular destruction and retinal destruction distinguishing from the group B.And the relative expression of VEGF protein of the group D and the group A was markedly lower than that of the group B(P < 0.01).The relative expression of PEDF protein of the group D and the group A was dramatically higher than that of the group B to the contrary(P < 0.01).Conclusions DHMMR demonstrates pronounced suppressive effects on the progression of DR after retinal laser photocoagulation,through down-regulating VEGF and upregulating PEDF.

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.

New frontiers in retinal transplantation

New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells.Thus,the disruption of photoreceptors takes place.However,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact.This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region.The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities.The eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant patients.The main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal regions.Recent progress has shown significant enhancements in transplant procedures and results.The research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding ESCs.The analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation.Moreover,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation.The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location.Currently,most therapy approaches are in the first phases of development and necessitate further research,including both pre-clinical and clinical trials,to attain favorable visual results for individuals suffering from retinal degenerative illnesses.

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.