玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab联合激光光凝治疗急进性后部型早产儿视网膜病变的疗效观察

目的 观察玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab（商品名Lucentis）联合激光光凝治疗急进性后部型早产儿视网膜病变（AP-ROP）的安全性和有效性。方法 经早产儿视网膜病变（ROP）筛查和临床检查确诊为AP-ROP的35例患儿70只眼纳入研究。所有患眼病变均位于后极部。其中，病变位于1区42只眼，病变位于2区28只眼。合并有虹膜新生血管或扩张的虹膜血管46只眼，合并玻璃体积血19只眼。所有患儿在确诊后12 h内接受玻璃体腔注射ranibizumab治疗。观察全身及眼部的不良反应情况。注药后1周，观察患眼眼底情况，比较玻璃体腔注射ranibizumab前后视网膜血管纡曲和扩张程度的变化。所有患眼均在玻璃体腔注射ranibizumab治疗后联合激光光凝治疗，激光治疗距离注药的时间间隔为1～10周，平均间隔时间（5.1±2.6）周。治疗后随访时间6～18个月，平均随访时间（10.3±3.9）个月。主要观察视网膜病变转归情况。对于随访过程中出现病情进展至4期或5期的患儿，行保留晶状体的玻璃体切割手术或玻璃体切割联合晶状体切除手术。结果 玻璃体腔注射ranibizumab后，无患儿发生眼部并发症及全身不良反应。出现新增的视网膜前出血12只眼，占所有患眼的17.1%；但出血均自行吸收。随访期间，所有的晶状体均保持透明，未发生医源性裂孔。玻璃体腔注射ranibizumab后1周，所有虹膜新生血管或扩张的虹膜血管均消退。玻璃体积血明显吸收16只眼，占合并有玻璃体积血患眼的84.2%。后极部血管纡曲、扩张明显消退61只眼，占所有患眼的87.1%；视网膜血管不同程度向周边生长59只眼，占所有患眼的84.3%。1区病变42只患眼中，血管发育至2区32只眼，占76.2%。2区病变28只患眼中，血管发育至2～3区交界处24只眼，占85.7%。玻璃体腔注射ranibizumab联合激光光凝治疗后，视网膜血管网或嵴消退、附加病变消退且视网膜平复62只眼，占所有患眼的88.6%。视网膜表面纤维增生膜持续加重，发生牵引性视网膜脱离8只眼，占所有患眼的11.4%。其中，进展至4期5只眼，占所有患眼的7.1%；进展至5期3只眼，占所有患眼的4.3%。接受保留晶状体的玻璃体切割手术4只眼，接受玻璃体切割联合晶状体切除手术4只眼。手术治疗后，视网膜完全复位5只眼，视网膜部分复位3只眼。结论 玻璃体腔注射ranibizumab联合激光光凝治疗AP-ROP安全、有效。

Combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity

Objective To observe the efficacy and safety of combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity (AP-ROP). Methods Medical records of 70 eyes of 35 premature infants with a primary diagnosis of AP-ROP in our clinic were reviewed and analyzed retrospectively. All the lesions were located in posterior zone, with 42 eyes in zone 1 and 28 eyes in zone 2. Forty six eyes had iris neovascularization, while 19 eyes combined with vitreous hemorrhage. All participants underwent intravitreal injection of ranibizumab as the primary treatment within 12 hours after diagnosis of AP-ROP. The systemic and ocular adverse effects were observed. The change of retinal vascular tortuosity and dilatation before and after the intravitreal injection of ranibizumab was observed one week after injection. Laser photocoagulation was used as adjuvant therapy if the plus disease persisted more than two weeks or new-onset ridge occurred after injection. The mean time interval between injection and laser therapy was (5.1±2.6) weeks (range, 1 -10 weeks). Follow up ranged from 6 to 18 months, with a mean of (10.3±3.9) months. The anatomical results and complications were evaluated after treatment. The eyes that progressed to stage 4 or 5 during the follow-ups were underwent lens sparing vitrectomy or lensectomy combined with vitrectomy. Results No major systemic or ocular complications were observed. Preretinal hemorrhages were found in 12 eyes of 8 patients (17.1%), but they were absorbed spontaneously during the follow ups. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-ups. After the injection, the regression of iris neovascularization was observed in 46 eyes within one week, vitreous hemorrhage absorbed significantly in 16 eyes (84.2%), and plus disease disappeared completely within one week in 61 eyes (87.1%). 59 eyes (84.3%) demonstrated vascularization toward the peripheral retina after treatment. 32 out of 42 eyes (76.2%) with zone 1 demonstrated vascularization toward to zone 2, while 24 out of 28 eyes (85.7%) with zone 2 demonstrated vascularization toward to the junction of zone 2 and 3. After intravitreal injection of ranibizumab combined with laser photocoagulation, 62 of 70 eyes (88.6%) had retinal vascular ridge and plus disease regression. However, 8 eyes of 6 patients (11.4%) showed significant fibrovascular proliferation and progressed to retinal detachment after the combination treatment of intravitreal ranibizumab injection and laser photocoagulation. Four eyes underwent lens-sparing vitrectomy, while the other 4 eyes underwent vitrectomy combined with lensectomy. Five eyes achieved totally retinal reattachment after surgery, while 3 eyes achieved partially retinal reattachment. Conclusion The combination of intravitreal injection of ranibizumab and laser photocoagulation is safe and effective in the treatment of AP-ROP.