Efficacy And Safety Of Intravitreous Injection Of Low Dose Of Aflibercept In The Treatment Of Retinopathy Of Prematurity

Background and purposeRetinopathy of prematurity(ROP),as a vascular proliferative disease that occurs in the immature retina.Mild cases can resolve spontaneously,while severe ROP various methods of intervention are needed in a timely manner.Intravitreal injection of anti-VEGF drugs has become one of the main methods for the treatment of ROP in many developing countries.Both ranibizumab and bevacizumab are humanized monoclonal VEGF antibody fragments for retinal vascular diseases.Intravitreal injection of ranibizumab is an effective treatment for ROP.And well tolerated methods.Aflibercept is a fusion protein with multiple targets,with stronger affinity and longer action time.A prospective study followed up to 1 year and found that after aflibercept treatment of ROP,good retinal anatomy and functional outcomes can be obtained.Previously,we conducted a small sample study on the treatment of ROP with reduced aflibercept intravitreal injection,and the results suggest that it is positive,but regarding the efficacy and safety of larger samples,especially the effect of aflibercept treatment on growth The effects of development are still unclear.The usual dose of anti-VEGF drugs to treat ROP is half that of adults,but VEGF is essential for neonatal development,especially the development of important organs such as the brain,kidneys,and lungs,and the half-life of aflibercept is longer than that of ranibizumab.The larger molecular weight may have a greater negative effect on the growth and development of premature infants.Therefore,this study used low-dose aflibercept(1/4 adult dose)and conventional dose ranibizumab(1/2 adult dose)to treat ROP,and evaluated and compared the efficacy,safety,growth and development parameters,etc.,with a view to Provide an effective reference for the follow-up clinical treatment of ROP.MethodsIn a non-randomized case-control study,children admitted to the First Affiliated Hospital of Zhengzhou University from October 2018 to September 2020 who were diagnosed with type 1 ROP,threshold ROP,and aggressive posterior ROP were included.Intravitreous injection of drugs(Ranibizumab or reduced dose of Aflibercept)was selected according to the guardian’s will.Anatomic outcomes,ocular and systemic complications were observed during the 6-month follow-up period.Effectiveness:subsidence of additional lesions,disappearance or reduction of retinal vascular tortuousness and formation of new blood vessels,peripheral growth of normal retinal vessels;Inefficacy:During the follow-up period,re-injection or laser treatment was needed for disease recurrence,and abnormal lesions such as ridge and additional lesions recurred.Intraocular pressure was measured and recorded 1 minute before and 1,10,and 30 minutes after treatment with both drugs.The data of growth parameters(including body weight,height and head circumference)were measured and recorded during the follow-up of the two groups before treatment,1 month after treatment and 2 months after treatment,and the Fenton-Z score was calculated according to the growth parameters.Using SPSS 22.0 statistical software for basic data and secondary data statistical analysis.Chi-square test is used to verify the difference in efficacy.The intraocular pressure,weight,height and head circumference at different time points before and after treatment are compared by two-factor analysis of variance and repeated measurement.If P<0.05,the difference was considered statistically significant.Results1.There was no significant difference in the basic count data and classification data between the two groups before anti-VEGF treatment(P>0.05 for both groups),so the follow-up efficacy and safety comparison between the two groups was comparable.2.By the end of the 6-month follow-up,the effective rate of ranibizumab group was 91.7%(44/48),and the inefficiency was 8.3%(4/48).Among them,3 eyes were effective after re-injection,and 1 eye which is APROP before treatment progressed to stage 5 ROP after treatment,underwent vitrectomy,and re-examination of the posterior macular retina was good.In the reduced aflibercept group,the effective rate was 87.0%(40/46)and the inefficiency was 13.0%(6/46)eyes.Among them,4 eyes were effective after reinjecting the same amount of aflibercept,and 2 eyes underwent retinal photocoagulation.Effective after surgery.The effective rate of a single treatment between the two groups was compared,and the difference was not statistically significant(χ2=0.17,P=0.69).3.There were significant differences in intraocular pressure between the two drugs after treatment,and the difference was statistically significant(F=40.4,P<0.01).The overall differences in intraocular pressure before and after drug treatment between the two groups at different time points were significant(F=809.1,P<0.05),The intraocular pressure of the ranibizumab group was significantly higher than that of the half dose aflibercept group at 1 minute and 10 minutes after treatment.Compared with the respective time points,it was found that 1 minute after treatment was significantly higher than 10 minutes,30 minutes after treatment and before treatment(P<0.01).There was no significant difference in intraocular pressure 30 minutes after injection and before injection between the two groups(P>0.05).4.No treatment-related ocular or systemic complications were observed in both groups5.There was no significant difference between the overall comparison groups(Fweight=0.01,Fgroup=0.02,F head circumference=0.02,P>0.05),two factors of repetitive measure analysis of variance,there was significant difference between 2 months after and 1 month after treatment in weight parameter,P aflibercept=0.02<0.05,P Ranibizumab=0.02<0.05,no significant difference to the rest of the parameters also.we can see in the treatment of two groups after 1 months weight,height,head circumference three growth parameters of the corresponding Z score decreased,but no significant difference(P>0.05).Conclusion1.0.5mg aflibercept is safe and effective for the retinopathy of prematurity2.Treatment of retinopathy of prematurity with 0.5mg aflibercept resulted in less intraocular pressure fluctuations.3.The two anti-VEGF drugs aflibercept and ranibizumab may have short-term limited negative effects on the growth of body weight,height,and head circumference parameters,but there is no long-term effect,and further close follow-up evaluation is still needed.