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).

NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration:potential therapeutic implications

Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.

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

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

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration

The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.

Oxidative stress in retinal pigment epithelium degeneration:from pathogenesis to therapeutic targets in dry age-related macular degeneration

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Identification of retinal thickness and blood flow in agerelated macular degeneration with reticular pseudodrusen

AIM:To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen(RPD)as an early detection strategy for age-related macular degeneration(AMD).METHODS:This retrospective study included 24 subjects(33 eyes)with RPD and 25 heathy control subjects(34 eyes).The superficial capillary plexus(SCP)and the deep capillary plexus(DCP)of the retinal posterior poles were investigated with optical coherence tomography angiography(OCTA).Retinal thicknesses and vessel densities were analyzed statistically.RESULTS:The general retinal thicknesses of RPD eyes were significantly decreased(95%CI-14.080,-0.655;P=0.032).The vessel densities of DCP in RPD eyes were significantly increased in the global(95%CI 1.067,7.312;P=0.027),parafoveal(95%CI 0.417,5.241;P=0.022),and perifoveal(95%CI 0.181,6.842;P=0.039)quadrants.However,the vessel densities of the SCP were rarely increased in the eyes with RPD.CONCLUSION:The thinning of retinas in the RPD group suggests a reduction in the number of cells.Additionally,the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply,possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina.This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.

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

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

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

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

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

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion

AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:This is a retrospective case control study.The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor(VEGF)for patients diagnosed with macular edema secondary to DR(DME)or RVO(RVO-ME)at Xijing Hospital from August 2021 to July 2022.Meanwhile,aqueous humor samples during vitrectomy from patients with idiopathic macular hole(IMH)were also collected and served as controls.The aqueous humor concentrations of VEGF,platelet-derived factor(PDGF),interleukin(IL)-6,IL-8,IL-18,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured with Human Premixed Multi-Analyte Kit(Luminex).The difference of the aqueous cytokines and the correlation between the two diseases were analyzed.RESULTS:A total of 40 eyes of 38 patients were enrolled in the study,including 13 eyes of 11 DME patients(DME group),16 eyes of 16 RVO-ME patients(RVO-ME group)and 11 eyes of 11 IMH patients(control group).The VEGF,PDGF,IL-6,IL-8,and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group(all P<0.05),the levels of TNF-αwas higher in the DME group than in the control group(P<0.05).The VEGF,IL-6,MCP-1,and TNF-αlevels in the aqueous humor were significantly higher in the DR group than those in the RVO group(all P<0.05).Correlation analyses revealed that there were complex positive correlations between IL-6,IL-8,IL-18,MCP-1,and TNF-αlevels in the aqueous humor of eyes with two diseases.CONCLUSION:Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME,the roles of these factors are more significant or more likely to be activated in DR patients,suggesting different treatment strategies should be considered for the two diseases.

Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model

Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus(AAV)vector encodingβ-catenin to treat AMD in a mouse model.Methods Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks,andβ-catenin expression was measured using immunofluorescence staining,real-time quantitative reverse transcription polymerase chain reaction(PCR),and Western blotting.The function ofβ-catenin was determined using retinal flat mounts and laser-induced damage models.Finally,the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections.Results AAV2/8-Y733F-VMD2-β-catenin induced the expression ofβ-catenin in RPE cells.It activated the proliferation of RPE cells and increased cyclin D1 expression.It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells.Furthermore,it could induce apoptosis of RPE cells by increasing the expression of Trp53,Bax and caspase3 while decreasing the expression of Bcl-2.Conclusion AAV2/8-Y733F-VMD2-β-catenin increasedβ-catenin expression in RPE cells,activated RPE cell proliferation,and helped mice heal from laser-induced eye injury.Furthermore,it could induce the apoptosis of RPE cells.Therefore,it may be a safe approach for AMD treatment.

Optical coherence tomography angiography for macular microvessels in ischemic branch retinal vein occlusion treated with conbercept:predictive factors for the prognosis

AIM:To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography(OCTA)in ischemic branch retinal vein occlusion(BRVO)patients with macular edema(ME)after anti-vascular endothelial growth factor(VEGF)treatment.METHODS:In this retrospective analysis,data from 60 patients(60 eyes)with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography(FFA)were studied.The eyes with ME according to spectral domain optical coherence tomography(SD-OCT)underwent intravitreal conbercept(IVC)and 3+pro re nata(PRN)regimen.The injection times were recorded.Two weeks after injection,fundus laser photocoagulation was performed in the non-perfusion area of the retina.The patients were followed up once a month for 6mo.The bestcorrected visual acuity(BCVA),foveal avascular zone(FAZ),and A-circularity index(AI),at 6mo and the baseline were compared.RESULTS:All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR(P<0.001).The mean central macular thickness(CMT)significantly decreased from 476.22±163.54 to 298.66±109.23μm.Both the FAZ area and AI at 6mo were significantly higher than those at the baseline:the FAZ area increased(0.38±0.02 vs 0.39±0.02 mm^(2),P<0.05);the AI increased(1.27±0.02 vs 1.31±0.01,P=0.000).The baseline BCVA showed a significantly positive correlation with the baseline FAZ area,FAZ perimeter(PERIM)and AI,final visual gain(FVG)and injection times,respectively(P<0.001).FVG showed a significantly negative correlation with the FAZ area,PERIM,AI and injection times,but a significantly positive correlation with vessel densities(VDs)300μm area around FAZ(FD-300;P<0.001).Injection times was positively correlated with the baseline FAZ area,and AI,but inversely correlated with the baseline FD-300(P<0.001).However macular ischemia was noted in 5 cases during follow-up.CONCLUSION:Using OCTA to observe macular ischemia and quantify parameters can better predict the final visual prognosis of patients before treatment.The changes in FAZ parameters may influence the visual prognosis and injection times.

Inflammation and retinal degenerative diseases

Vision is an ability that depends on the precise structure and functioning of the retina.Any kind of stress or injury can disrupt the retinal architecture and leads to vision impairment,vision loss,and blindness.Immune system and immune response function maintain homeostasis in the microenvironment.Several genetic,metabolic,and environmental factors may alter retinal homeostasis,and these events may initiate various inflammatory cascades.The prolonged inflammatory state may contribute to the initiation and development of retinal disorders such as glaucoma,age-related macular degeneration,diabetic retinopathy,and retinitis pigmentosa,which pose a threat to vision.In the current review,we attempted to provide sufficient evidence on the role of inflammation in these retinal disorders.Moreover,this review paves the way to focus on therapeutic targets of the disease,which are found to be promising.

Stem cell therapy in retinal diseases

Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness.Despite intensive research in the field of retinal disorders,there is currently no curative treatment.Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development.In the context of cell-based therapies,different cell sources such as embryonic stem cells,induced pluripotent stem cells,or multipotent stem cells can be used for transplantation.In the vast majority of human clinical trials,retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies.In this review,we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

Comparison of one and three initial monthly intravitreal ranibizumab injection in patients with macular edema secondary to branch retinal vein occlusion

AIM： To compare three initial monthly intravitreal ranibizumab（IVR） injections followed by pro re nata（PRN） dosing with one initial monthly IVR injections followed by PRN dosing for macular edema（ME） secondary to branch retinal vein occlusion（BRVO）.METHODS： Forty-two eyes of 42 patients who had IVR injections for BRVO were retrospectively studied. Eighteen eyes received 1 initial IVR injection（1＋PRN group） and 24 eyes received 3 monthly IVR injections（3＋PRN）. At 1, 3, 6 and 12mo; spectral-domain optical coherence tomography（SD-OCT） was performed. Central macular thickness（CMT）, the integrity of the external limiting membrane（ELM）, the presence of subretinal fluid, cyst size, the presence of inner segment/outer segment（IS/OS） defect were determined.RESULTS： At baseline the mean CMT was 521.3±153.2 μm in the 3＋PRN group while it was 438.1±162.4 μm in 1＋PRN group. At the final visit, mean CMT was 278.3±87.8 μm in the 3＋PRN group and 285.2±74.2 μm in the 1＋PRN group（P=0.079）. The changes in CMT over the entire study period were also comparable in both groups（243±160 μm in the 3＋PRN group, and 152.9±175.3 μm in the 1＋PRN group; P=0.090）. At baseline, best-corrected visual acuity（BCVA） was 0.92±0.60 logarithm of the minimal angle of resolution（logMAR） in the 3＋PRN group, while it was 0.72±0.46 logMAR in the 1＋PRN group. Final BCVA was 0.42±0.55 logMAR in the 3＋PRN group and 0.38±0.50 logMAR in the 1＋PRN group（P=0.979）. Additionally, the BCVA changes from baseline to final visit were not significantly different（-0.50±0.45 logMAR in the 3＋PRN group, and-0.33±0.39 logMAR in the 1＋PRN group; P=0.255）.CONCLUSION： No significant differences in the anatomical or functional results are found between 3＋PRN and 1＋PRN regimens in the patients receiving ranibizumab for ME secondary to BRVO. Intact IS/OS and baseline BCVA are good predictor of the visual gain, while baseline CMT is a good predictor of the anatomical gain.

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.

Intravitreal injection of bevacizumab alone or with triamcinolone acetonide for treatment of macular edema caused by central retinal vein occlusion

AIM: To compare the efficacy and safety of intravitreal bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with macular edema caused by central retinal vein occlusion (CRVO) in Chinese patients. METHODS: Seventy-five eyes of 75 patients were enrolled in this prospective, randomized, consecutive study. Thirty-six patients in group 1 were treated with an intravitreal injection of bevacizumab (1.25mg/0.05mL), and 39 patients in group 2 were treated with intravitreal bevacizumab (1.25mg/0.05mL) combined with triamcinolone acetonide (2mg/0.05mL). The main outcomes of the mean best corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) were measured. RESULTS: In group 1, the mean BCVA improved from 37.78 +/- 6.14 (baseline) to 48.06 +/- 3.86, 46.48 +/- 4.77 and 44.18 +/- 5.78 at four, six and twelve weeks post-injection, respectively (P<0.01, P=0.03, P=0.04). In group 2, the mean BCVA improved from 35.92 +/- 6.20 (baseline) to 50.69 +/- 4.22, 48.76 +/- 5.59 and 45.70 +/- 6.56 at the same time points (P<0.01 each). However, there was no significant differences in the mean BCVA (F=0.043, P=0.836) and CRT (F=0.374, P=0.544) between these two groups. During the follow-up, five patients in group 1 and six patients in group 2 with high IOP were controlled with anti-glaucoma drugs. CONCLUSION: Intravitreal injection of bevacizumab alone or combined with triamcinolone acetonide has a short beneficial effect in Chinese patients with macular edema caused by CRVO, but there is no significant difference between the two groups.

Macular and peripapillary retinal nerve fiber layer thickness in children with hyperopic anisometropic amblyopia

AIM:To compare the retinal nerve fiber layer (RNFL) thickness and macular thickness in the amblyopic eye with that in the sound eye of children with hyperopic anisometropic amblyopia using optical coherence tomography (OCT). METHODS:A prospective, nonrandom, intraindividual comparative cohort study includes 72 children with hyperopic anisometropic amblyopia in a single center. Macular thickness, macular foveola thickness, and peripapillary RNFL thickness were compared between the amblyopia eyes and the contralateral sound eyes. ·RESULTS:There were 38 male and 34 female patients, with a mean age as 9.7 ±1.9 years (range, 5-16 years). Hyperopic was +3.62±1.16D (range +2.00D to +6.50D) in the amblyopic eyes, which was significantly higher in the control eyes with +0.76±0.90D (range 0D to +2.00D) (P 【 0.01). The mean peripapillary RNFL thickness was 113.9± 7.2μm and 109.2 ±6.9μm in the amblyopic eye and the normal eye, respectively, reaching statistical significance (P = 0.02). The mean macular foveola thickness was significantly thicker in the amblyopic eyes than the contralateral sound eyes (181.4±14.2μm vs 175.2±13.3μm, P 【0.01), but the 1mm, 3mm or 6mm macular thickness central macular thickness was not significantly different. Degree of anisometropia in the contralateral eyes was not significantly correlated with differences of peripapillary RNFL, macular foveola thickness or central macular thickness. CONCLUSION:Eyes with hyperopic anisometropic amblyopia are found thicker macular foveola and peripapillary RNFL than the contralateral eyes in children.

Effect of suction on macular thickness and retinal nerve fiber layer thickness during LASIK used femtosecond laser and Moria M2 microkeratome

·AIM: To compare the effect of suction on the macular thickness and retinal nerve fiber layer(RNFL) thickness during laser in situ keratomileusis(LASIK) used Ziemer FEMTO LDV femtosecond laser(Ziemer group) and Moria M2 automated microkeratome(Moria group) for flap creation.· METHODS: Fourier-domain optical coherence tomography(FD-OCT) was used to measure macular thickness, ganglion cell complex thickness and RNFL thickness of 204 eyes of 102 patients with the Ziemer femtosecond laser(102 eyes) and the Moria M2microkeratome(102 eyes) before surgery and 30min; 1,3d; 1wk; 1, 3mo; 1y after surgery.· RESULTS: The average foveal thickness and parafoveal retinal thickness 30 min after the surgery were statistically more than that before surgery(Ziemer P 【0.001,P =0.003 and Moria P=0.001, P=0.006) and the effect was less in the Ziemer group than that in the Moria group(P all 【0.05). The ganglion cell complex thickness was not significantly changed in both groups(P all 】0.05). The RNFL thickness was statistically less 30 min after surgery in both groups(P=0.014, P 【0.001), but the influence was less in Ziemer group than that in Moria group(P =0.038).However, the RNFL thickness had recovered to the preoperative level only 1d after surgery.·CONCLUSION: The suction of femtosecond laser and mechanical microkeratome led to the increase in macular central fovea thickness and the decrease in RNFL thickness values at the early stage after LASIK. The effect of suction on macular and the RNFL thicknesses in Ziemer group is smaller than that in Moria group.

Comparison of intravitreal ranibizumab and bevacizumab for the treatment of macular edema secondary to retinal vein occlusion

AIMTo compare the efficacy of ranibizumab and bevacizumab for macular edema due to retinal vein occlusion (RVO).