雷珠单抗治疗湿性年龄相关性黄斑变性的疗效观察及其对患者血浆miRNA-126、VEGF-A表达的影响

目的 探讨玻璃体腔注射雷珠单抗治疗湿性年龄相关性黄斑变性(wAMD)的临床疗效,及其对患者血浆中微小RNA(miRNA)-126、血管内皮生长因子(VEGF)-A的表达水平的影响。方法 前瞻性研究。纳入2018年6月-2019年6月蚌埠医学院第一附属医院眼科收治40例(40只眼)wAMD患者为wAMD组,其中男17例、女23例,年龄50~86岁。纳入同期在蚌埠医学院第一附属医院体检中心进行健康体检的中老年人为对照组(40人),其中男18人、女22人,年龄53~81岁。wAMD组患者均接受单次玻璃体腔注射雷珠单抗0.05 mL治疗。采用实时荧光定量PCR(qPCR)法检测对照组和wAMD组治疗前及治疗后1个月血浆miRNA-126相对表达水平,酶联免疫吸附试验检测血浆中VEGF-A水平。(1)比较对照组、wAMD组治疗前miRNA-126及VEGF-A的表达水平。(2)比较wAMD组治疗前、治疗后1个月血浆miRNA-126、VEGF-A表达水平,以及最佳矫正视力(BCVA)、黄斑中央区视网膜厚度(CMT)、脉络膜新生血管(CNV)面积的变化情况。(3)分析wAMD组患者治疗前、治疗后1个月血浆miRNA-126的相对表达量与VEGF-A水平、CMT、CNV面积的相关性。结果 (1)wAMD组患者的miRNA-126相对表达量(0.86±0.11)低于对照组(1.04±0.10),VEGF-A水平(329.09±17.58)pg/mL高于对照组(295.74±14.80)pg/mL,差异均有统计学意义(t=8.010、9.179,P值均＜0.01)。(2)wAMD组治疗后1个月miRNA-126相对表达量(1.47±0.27)较治疗前(0.86±0.11)增加,VEGF-A水平(315.36±15.44)pg/mL较治疗前(329.09±17.58)pg/mL降低,差异均有统计学意义(t=19.410、8.048,P值均＜0.01);BCVA(0.45±0.11)较治疗前(0.83±0.16)增加,CMT与CNV面积分别为(296.53±21.52)μm,(0.58±0.18)mm²,较治疗前的(311.88±37.25)μm、(0.70±0.17)mm²均降低,差异均有统计学意义(t=12.667、3.602、4.906,P值均＜0.01)。(3)wAMD组患者治疗前及治疗后1个月血浆miRNA-126相对表达水平与VEGF-A、CMT、CNV面积均呈显著负相关(r_治疗前=-0.706、-0.723、-0.552,r_{治疗后1个月}=-0.783、-0.709、-0.620, P值均＜0.01)。治疗前拟合VEGF-A、CMT、CNV面积与miRNA-126相对表达量之间的线性回归方程分别为:$\hat{Y}$_VEGF-A=-112X_miRNA-126+426,$\hat{Y}$_CMT=-243X_miRNA-126+522,$\hat{Y}$_CNV=-0.84X_miRNA-126+1.42;治疗后线性回归方程分别为:$\hat{Y}$_VEGF-A=-45.64X_miRNA-126+382,$\hat{Y}$_CMT=-57.53X_miRNA-126+381,$\hat{Y}$_CNV=-0.41X_miRNA-126+1.18。结论 雷珠单抗可通过降低VEGF-A的表达,减少CMT及CNV面积,有效改善BCVA。雷珠单抗在取得临床疗效的同时,可能通过增强miRNA-126基因表达活性而延缓wAMD的进展。     

Medication-related osteonecrosis of the jaws associated with intravitreal administration of ranibizumab

Medication-related osteonecrosis of the jaws (MRONJ) is a well-known complication that, in the majority of cases, is related to antiresorptive agents. Numerous articles have described cases of MRONJ in bisphosphonate-naïve patients treated with anti-angiogenic agents administered via various routes. A single case of MRONJ after intravitreal injection of bevacizumab has been reported. We report a case of MRONJ after intravitreal injection of a different anti-angiogenic agent – ranibizumab – for the treatment of neovascular age-related macular degeneration, in a bisphosphonate-naïve patient. Although it may be a rare complication, patients treated with multiple doses of anti-angiogenic agents should be monitored for the possible early diagnosis of MRONJ.     

A systematic review and meta-analysis comparing intravitreal ranibizumab with bevacizumab for the treatment of myopic choroidal neovascularisation

Intravitreal injections of ranibizumab (IVR) and bevacizumab (IVB) have both been used as treatments for myopic choroidal neovascularisation. We aimed to produce a meta-analysis of published literature comparing IVR with IVB for the treatment of myopic choroidal neovascularisation, by searching electronic databases from January 1950 to March 2013. Our search produced three suitable studies that reported on 117 patients in total. The results of the meta-analysis demonstrated that the mean number of lines improvement after IVR appeared better compared with IVB [fixed effects model: SMD = 0.46, 95% CI (0.09, 0.83), z = 2.44, p = 0.01]. The number of patients who had a greater than 3 line improvement was similar between groups [fixed effects model: RR = 0.95, 95% CI (0.67, 1.32), z = 0.33, p = 0.74]. At follow up there was no difference in number of those who had an absence of leakage [fixed effects model: RR = 1.04, 95% CI (0.93, 1.16), z = 0.64, p = 0.52]. There was no statistical significance between the two groups in relation to the number of injections [random effects model: SMD = −0.25, 95% CI (−1.12, 0.61), z = 0.57, p = 0.57]. Early evidence therefore suggests that intravitreal injections of ranibizumab are comparable to intravitreal injections of bevacizumab in the treatment of myopic choroidal neovascularisation. Both treatments result in a statistically significant increase in visual acuity with high numbers of patients maintaining stable vision. Further studies are still needed to strengthen results.     

Photodynamic therapy in combination with ranibizumab versus ranibizumab monotherapy for polypoidal choroidal vasculopathy: A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis to compare the outcome and serious adverse effects of intravitreal ranibizumab (IVR) monotherapy vs. combined treatment of IVR and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy (PCV).MethodsA computerized online search was performed using PubMed, EMBASE, Cochrane Library, Web of Science and China National Knowledge Infrastructure (CNKI) database. The quality of included studies was evaluated according to the Newcastle-Ottawa Scale. Stata 11.0 software was used to do the Meta-analysis.ResultsAfter a detailed systematic review, 4 articles (5 study samples) were included for this meta-analysis. PCV eyes treated with PDT combined with IVR achieved better best-corrected visual acuity (BCVA) than IVR monotherapy group throughout a follow-up of 12(th) month (weight mean difference [WMD] in BCVA, 0.132; 95% CI, 0.029–0.234, p = 0.012). Further meta-analysis including studies with 24-month follow up period showed that BCVA at 24(th) month was also better in the combined treatment group than the monotherapy group (WMD in BCVA = 0.234; 95% CI, 0.071–0.398, p = 0.005). There were no significant differences both in serious ocular adverse effects and non-ocular adverse effects (p > 0.05) between two groups.ConclusionsTreatment of PCV by PDT combine with IVR is valuable in improving visual acuity and maintaining long term effectiveness. Given the inherent limitations of the included research, future studies are needed to further validate and update the findings in this area.     

DERMAL TOXICITY OF LINEAR ALKYLBENZENE SULPHONATE AND NICKEL IN GUINEA PIGS

Guinea pigs were dermally exposed to linear alkylbenzene sulphonate (LAS) or nickel or in combination. In general, lipid peroxidation, histamine contents, acid phosphatase, β-glucuronidase, alkaline phosphatase, and glutathione-S-transferase showed elevations when exposed simultaneously to LAS and Ni. The Ni contents also increased in the skin. Histologically the skin revealed more hyperkeratinization and degenerative changes when it was exposed simultaneously to LAS and Ni.