玻璃体腔重复注射雷珠单抗对新生血管性AMD视网膜色素上皮萎缩面积及脉络膜厚度的影响

背景 玻璃体腔注射雷珠单抗(IVR)是治疗新生血管性年龄相关性黄斑变性(nAMD)的有效方法,了解IVR对视网膜色素上皮(RPE)和脉络膜产生的可能影响有助于临床上更好地选择重复注射次数和时机.目前对nAMD患者接受IVR后RPE萎缩面积和脉络膜厚度变化的定量研究较少见. 目的 采用频域光相干断层扫描(OCT)技术探讨IVR对nAMD患眼RPE萎缩面积及脉络膜厚度的影响. 方法 采用前瞻性自身对照研究设计,连续纳入2015年1月至2015年6月在武汉大学人民医院就诊的nAMD患者41例41眼.所有患眼均接受0.05 ml雷珠单抗(10 mg/ml)玻璃体腔注射,每个月随访1次,连续随访12个月.分别于IVR前及IVR后3、6、12个月采用频域OCT仪中RPE高级定量分析软件测量患眼黄斑区RPE萎缩面积,采用加强深度扫描OCT(EDI-OCT)技术测量黄斑中心凹下脉络膜厚度,对比分析IVR前后RPE萎缩面积和脉络膜厚度的变化及其之间的关系,评估RPE萎缩面积和脉络膜厚度变化与IVR次数的相关性.结果 所有患者全部配合完成治疗和随访.IVR后患眼视力较IVR前均明显改善,注射前后不同时间点平均视力的总体比较差异有统计学意义(F=7.631,P＜0.001).患眼IVR注射前平均脉络膜厚度值为(264.55±100.95) μm,IVR后3、6、12个月分别为(247.42±105.46)、(246.81± 99.85)和(253.97±101.15) μm,注射前后患眼平均脉络膜厚度值的差异有统计学意义(F=2.030,P＜0.05),注射后各时间点患眼平均脉络膜厚度较注射前均明显变薄,差异均有统计学意义(均P＜0.05).患眼IVR前与IVR后各时间点平均RPE萎缩面积比较差异无统计学意义(F=0.116,P=0.951).患眼RPE萎缩面积减小值与脉络膜厚度降低值呈微弱负相关(r=-0.185),注射次数＞6次组和注射次数≤6次组患眼的RPE萎缩面积减小值和脉络膜厚度降低值间分别呈微弱正相关和负相关(r=0.297、-0.327),但均无统计学意义(P=0.248、0.282、0.103).随访12个月,RPE萎缩面积减小值和脉络膜厚度降低值与IVR次数均呈微弱的线性相关(rs=-0.266、0.342),但均无统计学意义(P=0.148、0.060).结论 IVR可使AMD患者中心凹下脉络膜萎缩变薄,但未发现引起明显的RPE萎缩.多次IVR并不加速RPE或脉络膜萎缩.

Influence of repetitive intravitreal ranibizumab for neovascular age-related macular degeneration on retinal pigment epithelium and choroidal thickness

Background Intravitreal injection of ranibizumab (IVR) is one of the most effective therapies for neovascular age-related macular degeneration (nAMD).Understanding the influence of IVR on retinal pigment epithelium (RPE) and choroidal thickness is helpful for us to choose the operative times and timing based on pharmacologic effects and tissue response.However,limited studies are available about quantitative analysis of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Objective This study was to report the changes of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Methods A prospective series cases-observational study was designed.Forty-one eyes of 41 consecutive patients with nAMD were enrolled in Renmin Hospital of Wuhan University from January 2015 to June 2015,and written informed consent was obtained from each patient prior to entering the cohort.The affected eyes received intravitreal injection of 0.05 ml ranibizumab (10 mg/ml) and then followed up monthly for 12 months.The RPE atrophy area around macula and subfoveal choroidal thickness were measured by a newly developed RPE analysis software spectral-domain optical coherence tomography (OCT) and enhanced depth imaging of SD-OCT (EDI-OCT),respectively,and the RPE atrophy area and choroidal thickness changes were compared before IVR and 3,6 and 12 months after IVR.The correlation between RPE atrophy area and choroidal thickness before and after IVR was analyzed.Results All the patients finished the treating procedure and follow up.The visual acuity (logMAR) after IVR was considerably improved in comparison with before IVR (F=7.631,P＜0.001).The mean subfoveal choroidal thickness value was (264.55 ± 100.95) μm before IVR,and that of 3,6,12 months after IVR was (247.42±105.46),(246.81± 99.85) and (253.97±101.15)μm,respectively,showing a significant difference among different time points (F =2.030,P ＜ 0.05),and the mean subfoveal choroidal thickness values 3,6,12 months after IVR were evidently thinned in comparison with before IVR (all at P＜0.05).No significant difference was found in RPE atrophic area among different time points (F=0.116,P =0.951).Weak linear correlations were seen between RPE atrophy area and choroidal thickness (r =-0.185),the RPE atrophy area change values and choroidal thickness change values between IVR ＞ 6 times and ≤ 6 times (r =0.297,-0.327),but these results were not statistically significant (P =0.248,0.282,0.103).At the end of the follow up,weak linear correlations were seen in RPE atrophy area change values and choroidal thickness change values with IVR times (r,=-0.266,0.342),but these results were not statistically significant (P =0.148,0.060).Conclusions IVR for nAMD can lead to subfoveal choroid atrophy instead of RPE atrophy.IVR does not accelerate the atrophy progression of both RPE and choroid.