Efficacy and safety of anti-vascular endothelial growth factor agents on corneal neovascularization: A meta-analysis

BACKGROUND Corneal neovascularization(CoNV)is the second major cause of blindness.Vascular endothelial growth factor(VEGF)inhibitors,e.g.,bevacizumab,have been used to prevent CoNV.AIM We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV.METHODS A literature search was conducted using three electronic databases.Mean difference(MD),standard mean difference(SMD),and relative risk(RR)are used to estimate the effect size.RESULTS Nine randomized controlled and three non-randomized trials were obtained.The pooled results demonstrated a significant reduction of CoNV area/Length(SMD=-1.17,95%CI:-1.58 to-0.75),best corrected visual acuity(MD=-0.54,95%CI:-0.91 to-0.17),and graft rejection(RR=0.44,95%CI:0.24 to 0.8)and failure(RR=0.39,95%CI:0.19 to 0.78)rates in the anti-VEGF group than the placebo group.A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo(RR=0.56,95%CI:0.30 to 1.06).Compared with a placebo,the unsynthesizable trials also support that bevacizumab improves visual acuity,CoNV,graft rejection,and failure rates.Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV.CONCLUSION Anti-VEGF agents,mainly bevacizumab,are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation.

Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation

BACKGROUND Intravitreal anti-vascular endothelial growth factor(IVA)injection is known to cause contraction of fibrovascular proliferation(FVP),when present in severe retinopathy of prematurity(ROP).AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant FVP.METHODS It was a retrospective study in which 36 eyes of 18 preterm babies who developed>4 clock hours of FVP in zone I or posterior zone II,were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of ranibizumab.Favorable structural outcome included resolution of plus disease and FVP without the development of tractional retinal detachment.Secondary outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional treatment.Adverse outcomes included progression to retinal detachment.RESULTS The mean gestational age of the 18 preterm babies was 30 wk(range 27-36),and mean birth weight was 1319 g(range 650-1980 g).Mean post-menstrual age(PMA)at the time of primary treatment was 35.5 wk(range 31-41 wk).All eyes showed regression of plus disease and FVP.5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA(n=2 eyes)or peripheral laser photocoagulation(n=3 eyes)respectively.16 out of 36(44%)reached retinal vascular maturation at final follow up at 5 years.CONCLUSION There was good resolution of severe posterior ROP with FVP with IVA,with retinal maturity of 44%at 5 year follow-up and a reactivation rate of 13.8%.When the IVA injection is given prior to 37 wk PMA,while disease is in phase 2,it is less likely to cause contracture of pre-existing FVP.

Efficacy of internal limiting membrane peeling for diabetic macular edema after preoperative anti-vascular endothelial growth factor injection

AIM:To explore the efficacy of minimally invasive vitrectomy(MIV)with or without internal limiting membrane(ILM)peeling on the treatment of diabetic macular edema(DME)in proliferative diabetic retinopathy(PDR)combining with preoperative anti-vascular endothelial growth factor(anti-VEGF)injection.METHODS:Totally 132 eyes(132 patients)diagnosed PDR with DME were included between June 2015 and June 2018 in Tianjin Eye Hospital.The single MIV treatment group included 68 eyes and the MIV combined with ILM peeling group included 64 eyes.Anti-VEGF drugs were injected intravitreally 1wk before the operation and the period of follow-up was 1 to 3y.Best-corrected visual acuity(BCVA),central retinal thickness(CRT),total macular volume(TMV),macular edema(ME)severity,intraocular pressure(IOP),and complications were recorded.Prognostic factors of visual acuity following ILM peeling were analyzed.RESULTS:The BCVA was higher than preoperative values at 1,3,6,and 12mo after surgery in both groups(all P<0.05).At 6 and 12mo,the BCVA of the combined group was significantly higher than that of the MIV only group(0.52±0.23 v/s 0.64±0.29 IogMAR,P=0.011 in 6mo;0.41±0.25\/s 0.52±0.25 IogMAR,P=0.008 in 12mo).Mean CRT values postoperative were significantly lower than preoperative values in both groups from the 1^(st) month(lmo 397.65±106.18 vs 451.94±118.88 μm in MIV only group;388.88±108.68 v/s 464.36±111.53 μm in combined group;both P<0.05)and decreased gradually.The differences between the two groups were statistically significant at 3,6,and 12mo(P=0.004,0.003,0.00 respectively).The TMV was decreased from the 3^(rd) month in the single treatment group(3mo 11.14±1.66 vs 12.20±2.09 mm^(3),P<0.05).At 12mo,the proportion of eyes with edema that had CRT more than 350μm was significantly lower than before surgery(13.24%vs 77.94%in MIV only group;1.56%vs 81.25%in combined group;both P<0.05).There was no significant difference in the recurrence incidence of macular epiretinal membrane,ME,transient IOP increase,vitreous rebleeding,or traction retinal detachment between the two groups.BCVA after ILM excision was positively correlated with the CRT and ME degree before and after surgery(r=0.430,0.485,respectively;P<0.05).CONCLUSION:MIV combined with ILM peeling accelerates the absorption of ME,improves vision,reduces the postoperative CRT and TMV,and reduces the recurrence rate of postoperative ME.

Macular hole closure following anti-vascular endothelial growth factor injection in an eye with myopic choroidal neovascularization

Dear Editor,I am Cheolmin Yun,from the Department of Ophthalmology,Korea University College of Medicine.I write to present a case report of a female patient with a myopic patient suffering from atrophic choroidal neovascularization（CNV）and a full thickness macular hole（FTMH）,who was treated with an intravitreal anti-vascular endothelial growth factor （VEGF） injection without vitrectomy.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet,China

AIM: To evaluate the outcomes of intravitreal antivascular endothelial growth factor(anti-VEGF) agents for patients with retinal vein occlusion(RVO) related-macular edema(ME) in Tibetan.METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients(93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People’s Hospital from Jan 2018 to December 2019 were collected.RESULTS: The mean patient age was 56.8±10.6y, 45(50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity(BCVA) significantly increased(52.2±21.8 letters) in comparison with the baseline(38.2±24.1 letters, P<0.001);while the central retinal thickness(CRT) significantly reduced(245.5±147.6 μm) in comparison with the baseline(504.1±165.2 μm, P<0.001). The 43.0% of the eyes gained≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted.CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.

Vascular endothelial growth factor trap-eye(Aflibercept) for the management of diabetic macular edema

Diabetic retinopathy(DR)is the most common cause of visual loss among working age individuals.Diabetic macular edema(DME)is an important complication of DR that affects around one third of the patients with DR.Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor(VEGF)antagonists.The index review discusses aflibercept(EYLEA-Regeneron Pharmaceuticals,Inc.,Tarrytown,New York,NY,and Bayer Healthcare Pharmaceuticals,Berlin,Germany)in the context of other VEGF antagonists currently available for the treatment of DME.A systematic search of literature was conducted on PubMed,Scopus,and Google Scholar with no limitation on language or year of publication.Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A(VEGF-A)along with a longer duration of action as compared to other VEGF antagonists.Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring.Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases.However,further studies are indicated to confirm the role,safety,and efficacy of aflibercept for DME.

Bilateral same-session intravitreal injections of antivascular endothelial growth factors

AIMTo document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.

Diabetic macular edema:Efficacy and safety of antivascular endothelial growth factor therapy

Diabetic retinopathy is one of the prominent causes of vision impairment in the working-age population in industrialized countries and is related to 1%-5% of cases of blindness in the world. Among patients with diabetic retinopathy, diabetic macular edema(DME) is the major reason of vision impairment and represents a significant public health problem. Previous studies demonstrated the role of vascular endothelial growth factor(VEGF) in diabetic retinopathy and DME pathogenesis, and also revealed the efficacy of anti-VEGF agents for the management of these disorders. This review summarizes the outcomes of clinical studies that evaluated the anti-VEGF therapy including pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. A significant number of clinical trials indicated favorable functional and anatomical results of anti-VEGF therapy for DME. Therefore, these agents should be considered an option in the treatment of DME in routine clinical practice.

Progress of anti-vascular endothelial growth factor therapy for ocular neovascular disease： benefits and challenges

publication. Study selection Clinical trials and case studies presented at medical conferences and published in peer-reviewed literature in the past decade were reviewed. Results Anti-VEGF agents have manifested great potential and promising outcomes in treating ocular neovascularization, though some of them are still used as off-label drugs. Intravitrea~ injection of anti-VEGF agents could be accompanied by devastating ocular or systemic complications, and intimate monitoring in both adult and pediatric population are warranted. Future directions should be focused on carrying out more well-designed large-scale controlled trials, promoting sustained duration of action, developing safer and more efficient generation of anti-VEGF agents. Conclusions Anti-VEGF treatment has proved to be beneficial in treating both anterior and posterior neovascular ocular diseases. However, more safer and affordable antiangiogenic agencies and regimens are warranted to be explored.

Anti-vascular endothelial growth factor： the future treatment of choroidal neovascularization in pathologic myopia

-yopia is the most common refractive disorder. High .myopia affects 27%-33% of all myopic eyes inAsia.1,2 ;The pathologic myopia （PM） is the most severe vision-threatening phenotype of high myopia.3 It is also the second most common cause of choroidal neovascularization （CNV） in Asia. Unlike age-related macular degeneration （AMD） which mostly effecting elders, PM causes severe vision loss in young adults, resulting in a significant impairment of their working ability.4 PM has become the second leading cause of low vision and blindness particularly among those aged at 40-49 years in some Asia countries.

Extended survival with metastatic pancreatic cancer under fruquintinib treatment after failed chemotherapy:Two case reports

BACKGROUND Pancreatic cancer is a highly malignant disease.After decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more limited.Anti-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic cancer.Preclinical data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune microenvironment.CASE SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 months.Patient 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 months.Moreover,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was observed.The patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)infection.The patient died in February 2023.Patient 2 also took two prior lines of chemotherapy and then local radiotherapy combined with S-1.After confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third line.After the patient had COVID-19 in December 2022,fruquintinib was discontinued.The patient died in January 2023 due to disease progression.CONCLUSION Both cases achieved a PFS benefit from later-line single-agent fruquintinib therapy.With its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.

Pharmacological adjuvants for diabetic vitrectomy surgery

Diabetic vitrectomy is a highly intricate surgical procedure performed during the advanced stages of diabetic retinopathy(DR).It is used to treat conditions such as tractional or combined retinal detachment,vitreous hemorrhage,and subhyaloid hemorrhage,which are all severe manifestations of proliferative DR.The results of the surgery are uncertain and variable.Vitreoretinal surgery has made significant progress since the early stages of vitrectomy.In the past ten years,advancements in intravitreal pharmacotherapy have emerged,offering new possibilities to improve the surgical results for our patients.Within the realm of medical terminology,an"adjunct"refers to a pharmaceutical or substance employed to aid or expedite the primary therapeutic intervention for a particular ailment.Their introduction has broadened the range of therapeutic choices that are accessible prior to,during,and following surgical procedures.This review article will specifically analyze the pharmacological adjuncts used in diabetic vitrectomy surgery,with a focus on their role in facilitating or aiding specific steps of the procedure.The implementation of this system of categorization offers benefits to the surgeon by allowing them to foresee potential difficulties that may occur during the surgical procedure and to choose the appropriate pharmacological agent to effectively tackle these challenges,thus enhancing surgical success rates.

Progress in the Treatment of DME

Diabetic macular edema (DME) is a common ocular complication of diabetes mellitus (DM) and an important cause of vision loss. The pathogenesis of DME is complex and can occur at any time of diabetic retinopathy (DR). Effective methods of treating DME are essential to prevent irreversible damage to visual function. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated their therapeutic efficacy in large randomized controlled trials and real-life observational studies. Clinicians need to consider various factors, such as efficacy, safety, accessibility, and cost, in the selection of various options. This review summarizes the current therapeutic approaches for DME to provide new references for the treatment of DM.

Vascular endothelial growth factor concentration in vitreous humor of patients with severe proliferative diabetic retinopathy after intravitreal injection of conbercept as an adjunctive therapy for vitrectomy

Background:Proliferative diabetic retinopathy(PDR)is a progressive stage of diabetic retinopathy featured by the formation of neovascular and proliferative membrane.Vascular endothelial growth factor(VEGF)acts as a pivot factor in the development of neovascularization.This study was to investigate the changes of intravitreal VEGF concentrations of severe PDR after intravitreal injection of conbercept(IVC)and its potential advantages to the following vitrectomy.Methods:This was a prospective,interventional,randomized controlled study.Sixty eyes(60 patients)with severe PDR and 20 eyes from 20 patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy were enrolled in this study.PDR eyes were randomly assigned to three groups by sortation randomization method with 20 eyes in each based on the interval of preoperative IVC(group A:7 days,group B:14 days,group C:non-IVC).Another 20 eyes without diabetes were enrolled as the non-diabetic control group(group D),receiving PPV directly.Vitreous specimens of all 80 patients were collected and evaluated afterwards.The intravitreal VEGF concentration of the four groups,and the total surgical time and the intraoperative bleeding rate of the PDR groups were recorded.Results:The mean intravitreal VEGF concentrations of groups A-D were 66.6±43.3,93.1±52.3,161.4±106.1 and 1.8±1.2 pg/mL,respectively.It increased significantly in PDR patients(groups A,B and C)(P=0.002,<0.001,and<0.001,respectively).PDR patients with preoperative IVC(groups A and B)presented significantly lower VEGF concentrations(P<0.001 and 0.001),intraoperative bleeding rates(P=0.004)and total surgical time(P<0.001,P=0.003)compared with group C.No statistical differences were presented between groups A and B on the three parameters.Conclusion:Seven days and 14 days of preoperative IVC are equally efficient and safe for the vitrectomy of severe PDR patients through decreasing vitreous VEGF concentrations,intraoperative bleeding rate and total surgical times.

Correlation of Vascular Endothelial Growth Factor Production with Photochemical Reaction-induced Retinal Edema

Background： Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model. Methods： A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography （FP）, optical coherence tomography （OCT）, and fluoresce in fundus angiography （FFA） at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay （ELISA） and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1. Results： Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group （26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P 〈 0.01）; the mean RT （278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P 〈 0.05） and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 （P 〈 0.05）. Conclusions： This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.

Prognostic factors of short-term outcomes of intravitreal ranibizumab in diabetic macular edema

AIM：To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab（IVR） for diabetic macular edema（DME）.METHODS：Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity（BCVA） between 20/400 and 20/40. BCVA and central subfield thickness（CST） at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month 3.RESULTS：Younger age, poorer baseline BCVA and proliferative diabetic retinopathy（PDR） were correlated with better visual improvement at month 3（P=0.002, 0.0001 and 0.007, respectively）. Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST（P〈0.0001 and P=0.018, respectively）. The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide（PSTA） were associated with a smaller reduction in CST（P=0.029 and 0.018, respectively）, but had no significant effects in visual improvement at month 3（P〉0.05 for both）.CONCLUSION：For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022)

Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal pigment epithelium detachment(PED),extensive subretinal or vitreous hemorrhages,and severe vision loss.China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes,regarding opinions on inactive PCV,choices of anti-vascular endothelial growth factor(anti-VEGF)monotherapy,photodynamic therapy(PDT)monotherapy or combined therapy,patients with persistent subretinal fluid(SRF)or intraretinal fluid(IRF)after loading dose anti-VEGF,and patients with massive subretinal hemorrhage.An evidence synthesis team conducted systematic reviews,which informed the recommendations that address these questions.This guideline used the GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)approach to assess the certainty of evidence and grade the strengths of recommendations.Results The panel proposed the following six conditional recommendations regarding treatment choices.(1)For patients with inactive PCV,we suggest observation over treatment.(2)For treatment-na?ve PCV patients,we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy.(3)For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment,we suggest later/rescue PDT over initiate PDT.(4)For PCV patients who plan to initiate anti-VEGF monotherapy,we suggest the treat and extend(TE)regimen rather than the pro re nata(PRN)regimen following three monthly loading doses.(5)For patients with persistent SRF or IRF on optical coherence tomography(OCT)after three monthly anti-VEGF treatments,we suggest proceeding with anti-VEGF treatment rather than observation.(6)For PCV patients with massive subretinal hemorrhage(equal to or more than four optic disc areas)involving the central macula,we suggest surgery(vitrectomy in combination with tissue-plasminogen activator(tPA)intraocular injection and gas tamponade)rather than anti-VEGF monotherapy.Conclusions Six evidence-based recommendations support optimal care for PCV patients'management.

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.

Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration

·AIM:To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor(VEGF)injections to treat neovascular agerelated macular degeneration(n AMD)with subretinal fluid(SRF)and pigment epithelial detachment(PED).·METHODS:This prospective study included eyes with n AMD previously treated with as-needed anti-VEGF injections.The patients were treated with six monthly intravitreal injections of ranibizumab.Quantitative volumetric segmentation analyses of the SRF and PED were performed.The main outcome measures included best-corrected visual acuity(BCVA),and SRF and PED volumes.·RESULTS:Twenty eyes of 20 patients were included in this study.At the 6-month follow-up,BCVA and PED volume did not change significantly(P=0.110 and 0.999,respectively)but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3(P=0.002).The absorption rate of the SRF volume was negatively correlated with the duration of previous antiVEGF treatment(P=0.029).Seven of the 20 eyes(35%)showed a fluid-free macula and significant improvement in BCVA(P=0.036)by month 6.·CONCLUSION:Quantifying the SRF can precisely determine the patient’s responsiveness to anti-VEGF treatment of n AMD.