玻璃体腔注射个体化剂量康柏西普治疗早产儿视网膜病变的疗效观察

Individual dose of intravitreal conbercept for efficacy in retinopathy of prematurity

目的观察玻璃体腔注射个体化剂量康柏西普治疗1型阈值前早产儿视网膜病变(ROP)的疗效及安全性。方法回顾性病例研究。2019年1~7月在潍坊眼科医院检查确诊的1型阈值前ROP患儿23例46只眼纳入研究。其中,男性14例28只眼,女性9例18只眼。患者平均出生胎龄(28.06±1.73)周;平均出生体重(1.14±0.19)kg;首次玻璃体腔注射康柏西普(IVC)时平均矫正胎龄(34.38±1.41)周。首次IVC前采用A型超声测量患儿眼轴长度(AL)。根据AL计算对应的注射剂量范围,AL分别为14.23~16.19、16.20~17.57、17.58~18.63 mm的患儿,其康柏西普注射剂量分别为0.015、0.020、0.025 ml(分别含康柏西普0.15、0.20、0.25 mg)。所有患儿首次IVC剂量均为0.015 ml。首次IVC前1 d以及IVC后1、7 d,抽取患儿动脉血2 ml,检测血清血管内皮生长因子(VEGF)浓度。治疗后随访时间≥1年。随访1年后首次IVC治疗有效率、复发率采用χ^(2)检验;注射次数、注射间隔时间、视网膜血管化时间以及患儿血清VEGF浓度的短期变化采用t检验。结果首次IVC后1~3周,所有患眼视网膜新生血管消退,血管纡曲减轻;虹膜新生血管消退。首次IVC后1年内,16只眼因视网膜有无血管区交界处出现新生血管行第2次IVC。患儿行第2次IVC时的平均矫正胎龄为(40.56±3.81)周。康柏西普注射剂量0.015、0.020 ml者分别为2、14只眼。第2次与首次IVC平均间隔时间(40.89±8.99)d。行第2次IVC的16只眼中,8只眼因视网膜有无血管区交界处再次出现新生血管行第3次IVC。患儿行第3次IVC时的平均矫正胎龄为(43.00±1.41)周。康柏西普注射剂量0.020、0.025 ml者分别为3、5只眼。第3次与第2次IVC平均间隔时间(28.60±6.07)d;第3次与首次IVC平均间隔时间(69.20±12.40)d。终止随访时,所有患眼治疗有效(100%,46/46)。其平均注射次数(1.52±0.76)次;视网膜血管化时间为平均矫正胎龄(46.31±3.42)周。首次IVC前1 d及IVC后1、7 d,患儿血清平均VEGF浓度分别为(111.21±148.71)、(25.60±27.71)、(42.99±38.01)pg/ml.IVC后1、7 d患儿血清VEGF浓度较IVC前明显降低,差异有统计学意义(Z=-4.054、-2.779,P<0.05);IVC后7 d患儿血清VEGF浓度较IVC后1 d升高,差异有统计学意义(Z=-2.505,P<0.05)。所有患眼均未行激光光凝或玻璃体切割手术治疗;未见与药物或治疗方式相关的晶状体混浊、眼内炎、视网膜脱离等眼部并发症发生。结论玻璃体腔注射个体化剂量康柏西普治疗1型阈值前ROP有效;治疗后7 d患儿血清VEGF浓度降低。

Objective To observe the efficacy and safety of individual dose of intravitreal conbercept(IVC)in the treatment of retinopathy of prematurity(ROP)before type 1 threshold.Methods A retrospective case study.From January to July,2019,23 cases(46 eyes)of children with type 1 pre-threshold ROP were included in the study.Among them,14 cases(28 eyes)were male and 9 cases(18 eyes)were female.The mean gestational age at birth was 28.06±1.73 weeks.The average birth weight was 1.14±0.19 kg.The mean corrected gestational age was 34.38±1.41 weeks at the time of first intravitreal injection of IVC.The axial length(AL)of children was measured by A-mode ultrasound before IVC for the first time.According to the calculation of AL,the corresponding injection dose range was 14.23-16.19,16.20-17.57,17.58-18.63 mm and the injection dose of IVC was 0.015,0.020,0.025 ml(including IVC was 0.15,0.20,0.25 mg,respectively).The first IVC dose was 0.015 ml.On the first day before IVC and on the first and seventh days after IVC,2 ml of arterial blood was taken from children,serum vascular endothelial growth factor(VEGF)concentration was detected.The follow-up time after treatment was≥1 year.After one year of follow-up,the effective rate and recurrence rate of IVC for the first time were tested byχ^(2) tests.The short-term changes of injection times,injection intervals,retinal vascularization time and serum VEGF concentration in children were tested by t test.Results Retinal neovascularization subsided and vascular buckling decreased in all eyes.Iris neovascularization subsided,1-3 weeks after IVC for the first time.Within one year after the first IVC,16 eyes underwent IVC twice with or without new blood vessels at the junction of the vascular area.The average corrected gestational age was 40.56±3.81 weeks.The injection dose of IVC was 0.015 ml and 0.020 ml for 2 eyes and 14 eyes,respectively.The mean interval from IVC for the first time was 40.89±8.99 days.Of the 16 eyes who underwent IVC twice,8 eyes showed neovascularization again in the retinal area with or without blood vessels.The average corrected gestational age was 43.00±1.41 weeks.The injection dose of IVC was 0.020 ml and 0.025 ml for 3 eyes and 5 eyes,respectively.The mean interval of the second IVC was 28.60±6.07 days.The mean interval from the first IVC was 69.20±12.40 days.At the end of follow-up,all eyes were treated effectively(100%,46/46).The mean time of retinal vascularization was 46.31±3.42 weeks.The average number of injections was 1.52±0.76.On the first day before IVC and on the first and seventh days after IVC,the average serum VEGF concentrations were 111.21±148.71,25.60±27.71 and 42.99±38.01 pg/ml,respectively.Serum VEGF concentration was significantly lower than that before IVC on the 1st and 7th day after IVC(Z=-4.054,-2.779;P<0.05).Serum VEGF concentration was higher 7 days after IVC than 1 day after IVC,and the difference was statistically significant(Z=-2.505,P<0.05).All eyes were not treated by laser photocoagulation or vitrectomy.No eye complications such as lens opacification,endophthalmitis and retinal detachment related to drugs or treatment methods were found in all patients.Conclusion Intravitreal injection of individualized dose of IVC is effective in the treatment of type 1 pre-threshold ROP.Seven days after treatment,serum VEGF concentration of patients’serum decreases.