The Clinical Effect Of Conbercept On Wet Age-related Macular Degeneration And Analysis Of Its Prognostic Factors

Part Ⅰ The clinical effect of conbercept in the new standardized treatment of wet age-related macular degeneration[Background]Age-related macular degeneration(AMD)is one of the major causes of irreversible blindness in the elderly,which is obviously related to age.AMD can be divided into dry and wet types,which are also known as non-neovascular and or neovascular AMD.The damages of wet AMD is serious to the visual acuity,which is difficult to treat and has a relatively poor prognosis.At present,the main method of treatment of wet AMD is intraocular injection of anti-VEGF drugs,such as:ranibizumab,bevacizumab,aflibercept and conbercept.These drugs need long-term follow-up and frequent injection to have good therapeutic effect.Frequent drug administration will not only increase the economic burden of patients,but also bring serious complications such as endophthalmitis.Therefore,after many elderly patients get good vision benefits,they do not continue treatment,and irregular drug injection is not uncommon.Conbercept is the first anti VEGF drug independently developed in China,which has many characteristics such as multiple targets,strong affinity and long action time.A phase 3 study has confirmed the safety and efficacy of 3+Q3M strategy(one injection every month in the first 3 months,followed by one injection every 3 months)for the treatment of wet AMD.In this study,we retrospectively analyzed the clinical outcomes of two regimens of intravitreal injections of conbercept[1+pro re nata(PRN)and 3+Q3M]for the treatment of wet AMD,and further confirmed the clinical feasibility and importance of standardized treatment.[Objective]:This retrospective study aimed to analyze the clinical outcomes of two regimens of intravitreal injections of conbercept[1+pro re nata(PRN)and 3+Q3M]for the therapy of wet age-related macular degeneration(AMD)[Methods]:In total,105 eyes diagnosed with wet AMD were enrolled.The eyes in the 1+PRN group(n=51)received intravitreal injection of conbercept one time,followed by PRN retreatment.The eyes in the 3+Q3M group(n=54)received intravitreal injection of conbercept on three consecutive monthly,subsequently,once every three months for three times.After treatment,patients were followed up for 12 months.The best-corrected visual acuity(BCVA),central retinal thickness(CRT),and choroidal neovascularization(CNV)leakage area were compared before and after treatment.Moreover,the number of injections and adverse reactions were recorded[Results]Baseline characteristics did not differ significantly between the two groups.In I+PRN group,the mean BCVA was 0.84=10.38LogMAR at baseline,mean BCVAs were 0.54±0.32.0.50±0.29、0.48±0.26、0.50±0.25LogMAR at months 1/3/6/12,respectively.Significant improvements in vision were observedat each follow-up visit compared with baseline values(p<0.05).In 3+Q3M group,the mean BCVA was 0.81±0.39LogMAR at baseline,mean BCVAs were 0.52±0.31、0.36±0.26、0.31±0.24、0.33±0.23LogMAR at months 1/3/6/12,respectively.Significant improvements in vision were observedat each follow-up visit compared with baseline values(p<0.05).In 1+PRN group,the mean central retinal thickness was 432.74±69.81 μm at baseline,mean CRTs were 286.94±54.27、266.53±40.07、258.15±40.03、256.34±40.22μm,at months 1/3/6/12,respectively.The CRT was remarkably decreased compared with baseline values(p<0.05).In 3+Q3M group,the mean central retinal thickness was 425.38±71.02μm at baseline,mean CRTs were 279.87±57.62、239.17±37.71、233.01±37.86、235.91±3 8.03 μm,at months 1/3/6/12,respectively.The CRT was remarkably decreased compared with baseline values(p<0.05).A significant difference was observed in term of the mean improvement of BCVA and decrease of CRT between the two groupsat months 3/6/12.For 3+Q3M group,the BCVA improvenent and CRT decrease were more than that of 1+PRN group(p<0.05).FFA and ICGA at month 12 showed that the exudation had completely disappeared in 26(51.0%)and 32(59.3%)eyes in the 1+PRN and 3+Q3M groups,respectively.In addition,the exudation had decreased in 17(33.3%)and 18(33.3%)eyes in the 1+PRN and 3+Q3M groups,respectively.The area of exudation remained unchanged or increased in eight(15.8%)and four(7.4%)eyes in the 1+PRN and 3+Q3M groups,respectively.The differences between the two groups were not statistically significant(P>0.05).The mean number of injection in the 1+PRN group was 5.14±0.93;six injections were given to the 3+Q3M group.A significant difference was observed between two groups(p<0.05).During the follow-up,there were no serious adverse reactions or ocular complications.[Conclusions]This study reveals that intravitreal injection of conbercept using 3+Q3M regimen has certain advantages than 1+PRN regimen in extending drug delivery interval,improving patient’s vision,and reducing CRT.Part Ⅱ Different conbercept injection strategies for the treatment of wet age-related macular degeneration[Background]:Wet AMD has become a serious social and public health problem because of its serious impact on the quality of life of the elderly.Anti-VEGF drugs can prevent the growth of choroidal neovascularization by combining with VEGF receptor,then reduce retinal edema and exudation.At present,it has become the first choice of treatment for wet AMD.The clinical guideline for the treatment of wet AMD is formulated by the Chinese Ocular Fundus Diseases Socoety.The 3+PRN strategy(one injection every month in the first 3 months,followed by injection as-needed)is recommended,which is widely used.A recent multicenter,randomized,double-blind,sham-injection controlled phase Ⅲ clinical trial(PHOENIX)has demonstrated that the 3+Q3M injection strategy of conbercept is safe and effective for the treatment of wet AMD.At present,no study has directly compared these two strategies yet.Therefore,the aim of the present study was to compare the effectiveness,injection times,and adverse effects of the 3+Q3M and 3+PRN strategies in patients with wet AMD.[Objective]:To assess the effectiveness of intravitreal injection of conbercept using the 3+PRN and 3+Q3M strategies for the treatment of wet AMD.[Methods]:From 01/2016 to 01/2018,patients confirmed with wet AMD at Qilu Hospital of Shandong University were included in this retrospective study.Intravitreal injection of 0.5 mg of conbercept was conducted either with the 3+PRN or 3+Q3M strategy.The patients were followed for 12 months.Best corrected visual acuity(BCVA),intraocular pressure(IOP),and optical coherence tomography(OCT)were conducted at 1 and 2 weeks,then every month.FFA examination was conducted every 3 months.[Results]:Baseline characteristics did not differ significantly between the two groups.The BCVA before treatment in the 3+PRN and 3+Q3M groups was0.81±0.22 and 0.79±0.21 logMAR,respectively(P>0.05).The BCVA in both groups at month 1 to 12 was significantly better than baseline(all P<0.05).The BCVA values at months 7 and 9 to 12 in the 3+Q3M group were lower than in the 3+PRN group(all P<0.05).The CRT before treatment in the 3+PRN and 3+Q3M groups was 438.72±61.23 μm and 451.19±57.64 μm,respectively(P=0.284).The CRT values in both groups at months 1 to 12 were significantly better than baseline(all P<0.05).The CRT at month 9 to 12 in the 3+Q3M group was lower than in the 3+PRN group(all P<0.05).FFA and ICGA at month 12 showed that the exudation had completely disappeared in 31(56.4%)and 32(62.7%)eyes in the 3+PRN and 3+Q3M groups,respectively.In addition,the exudation had decreased in 18(32.7%)and 15(29.4%)eyes in the 3+PRN and 3+Q3M groups,respectively.The area of exudation remained unchanged or increased in six(10.9%)and four(7.8%)eyes in the 3+PRN and 3+Q3M groups,respectively.The differences between the two groups were not statistically significant(P=0.764).During the follow-up,there were no serious adverse reactions or ocular complications.[Conclusion]:The 3+PRN and 3+Q3M strategies of intravitreal injection of conbercept are effective in treating wet AMD.The 3+Q3M strategy needs more injection but is more effective in increasing visual acuity and reducing macular CRT than the 3+PRN strategy.PART Ⅲ Analysis of factors influencing the visual prognosis of wet age-related macular degeneration[Background]:Exudation,bleeding,and fibrous scar caused by choroidal neovascularization(CNV)are the major causes of visual loss in wet AMD.The vascular endothelial growth factor(VEGF)plays an important role in CNV,and has become the major target for the treatment of CNV.Although anti-VEGF therapy has been a breakthrough in the treatment of wAMD,unfortunately,up to a quarter of anti-VEGF-treated wAMD patients might not beneft from intravitreal injections and choroidal neovascularization(CNV)activity does not respond to the treatment.Under standing the predictive factors associated with visual acuity outcome and treatment response to anti-VEGF therapy may help retina specialists to manage patients’expectations and guide treatment decisions at treatment initiation.Optical coherence tomography(OCT)is a routine examination method in the process of treatment and follow-up.The changes of the structure of retina observed by OCT are related to the prognosis of vision.Hyper reflective dots(HRD)have been confirmed to be associated with visual outcome in wAMD.Conbercept is the first anti-VEGF fusion protein developed by Chinese researchers,and has the advantages of multiple targets,high affinity,and long effective time.The safety and effectiveness of conbercept have been confirmed.To analyse the possible factors that influence the prognosis of wet age-related macular degeneration has become the focus of attention.[Objective]:To observe the changes of visual acuity and OCT after conbercept treatment of wet age-related macular degeneration(wAMD),and analyze the related factors that affect the prognosis of visual acuity。[Methods]:From 06/2016 to 01/2018,58 patients confirmed with wAMD at Qilu Hospital of Shandong University were included in this retrospective study.Intravitreal injection of 0.5 mg of conbercept was conducted with the 3+PRN strategy.Collect basic information about patient’s age,sex,course of disease,optical coherence tomography(OCT)was used to detect the central retinal thickness(CRT)of macular.The integrity of ellipsoid zone(EZ),the external limiting membrane(ELM)and the number of hyper reflective dots(HRD)was analyzed.The patients were followed for 6 months.,and then were divided into two groups according to the final visual:the effective group(increased vision)and the ineffective group(stable and decreased vision).The influencing factors of BCVA after treatment were analyzed by multivariate Logistic regression analysis.[Results]:After 6 months of treatment BCVA increased from 1.10 士 0.42 LogMAR to 0.41±0.18 LogMAR,the difference was statistically significant(P<0.05);CRT decreased from 440.38±61.0 μm to 260.01±24.86 μm,the difference was statistically significant(P<0.05);the total number of HRD and the number of each layer were significantly reduced before treatment,the difference was statistically significant(P<0.05).There were 22 cases in the effective group and 36 cases in the ineffective group.By single factor analysis,there were significant differences in age,the baseline BCVA,the number of HRD at subretinal laye and ELM integrity between the two groups(P<0.001).Multiariable Logisticregression analysis showed that age,BCVA,the number of HRD at subretinal layer and ELM integrity-missing are independent risk for patients with wAMD treated by conbercept.[Conclusion]:The curative effect of intravitreal injection of conbercept is significant on wet AMD and safety is good.The poor BCVA recovery in some patients is effected by age,BCVA,the number of HRD at subretinal layer and the integrity of ELM before treatment.The above factors should be fully evaluated before treatment for further optimizing the curative effect.