8月 | Vesber 最佳RIO论文推荐
R——Retina推荐
A RANDOMIZED PAIRED-EYE TRIAL OF INTRAVITREAL DEXAMETHASONE IMPLANT FOR CYSTOID MACULAR EDEMA IN RETINITIS PIGMENTOSA
玻璃体腔注射地塞米松治疗视网膜色素变性黄斑囊样水肿的随机双眼试验
Purpose ：To evaluate the effificacy and safety of intravitreal dexamethasone (DEX) implant in retinitis pigmentosa patients with cystoid macular edema (CME).
目的：评价玻璃体腔注射地塞米松（DEX）治疗视网膜色素变性伴黄斑囊样水肿（CME）的有效性和安全性。
Methods ：In this randomized, noncontrolled, paired-eye, single crossover clinical trial, one eye of retinitis pigmentosa patients with bilateral CME with central macular thickness of>250 μm was randomized to intravitreal DEX implant while the fellow eye was observed. Both eyes were started on topical dorzolamide. At Month 6, DEX implant was eligible for both eyes when CME was >250 μm. Patients were followed up until Month 12. Primary outcome measures were the central macular thickness and best-corrected visual acuity changes from baseline at Month 2.
方法：在这个随机、无对照、配对、单交叉临床试验中，将双侧黄斑中心厚度>250μm的视网膜色素变性患者1只眼随机分为玻璃体内DEX注射，另1只眼作为对照同期观察。两眼在开始都有局部使用多唑胺。在第6个月，当CME为 >250 μm时，DEX植入物可用于双眼。随访至第12个月。主要观察指标为第2个月时黄斑中心厚度和最佳矫正视力变化。
Result ：Fourteen patients with bilateral RP-CME were included. Study eyes showed signifificant central macular thickness decrease (median, 2147.5 μm; P = 0.001) and best-corrected visual acuity improvement (median, +6 letters; P = 0.001) at Month 2, but not at Month 6. Intravitreal DEX implant at Month 6 produced comparable effificacy to baseline treatment in 11 fellow eyes and 12 study eyes. Topical dorzolamide did not show signifificant therapeutic effificacy. During 12 months, elevated intraocular pressure of .21 mmHg and cataract progression were observed in 14.3% and 40.0% of study eyes.
结果：包括14例双侧RP-CME患者。研究眼在第2个月时黄斑中央厚度显著降低（中值，2147.5 μm； P = 0.001）和最佳矫正视力改善（中位数，+ 6个字母； P = 0.001），但在第6个月差异则不再显著。在第6个月时，玻璃体内DEX注射在12个研究眼中有11个对比基线有显著疗效。多唑胺外用治疗效果较基线对比则不明显。在12个月内，研究眼观察中并发14.3%的高眼压和40.0%的白内障。
Conclusion ：Intravitreal DEX implant can both reduce macular thickness and improve vision in RP-CME, while repeated injection is required.
结论：在RP-CME中，玻璃体内注射DEX既能减轻黄斑厚度，又能提高视力，但需反复注射。
推荐理由：
采用对色素性视网膜炎黄斑囊性水肿的眼球注射地塞米松进行了对眼随机试验，由此来探讨这种方法的安全性和有效性。 本文的特别之处在于：1.这个试验是随机的、无对照的、双盲的、单交叉的。 2.这个试验采用了对侧眼数据来进行对比。这样的数据更具备参考性。
局限性：1，样本数量仅有14例，这个数量不足以说明试验的结果； 2，观察时间虽然有6个月-12个月，但是实际上除开最有效果的前两个月，其他时间并没有发现变化和记录，这是否说明观察方式有待改善； 3，对侧眼影响因素，由于双眼共用同一套血液循环，术眼的进行药物注射是否对于对侧眼有影响，文中并没有描述。
I——Investigative Ophthalmology & Visual Science 推荐
Combined Transplantation With Human Mesenchymal Stem Cells Improves Retinal Rescue Effect of Human Fetal RPE Cells in Retinal Degeneration Mouse Model
与人间充质干细胞联合移植可提高胎RPE细胞在视网膜变性小鼠模型中的视网膜修复作用
Purpose ：We verified whether fetal RPE (fRPE) cells and mesenchymal stem cells (MSCs) cotransplantation can combine the features of these two cell types and alleviate retinal degeneration in a retinal degenerative disease mouse model.
目的：通过视网膜退行性疾病的小鼠模型，确认人胎视网膜色素上皮细胞(fRPE)和间充质干细胞(MSCs)联合移植是否能结合这两种细胞的特点，从而达到缓解视网膜变性的目的。
Methods：Tail vein injection of sodium iodate (NaIO3) was conducted to establish the retinal degenerative disease mouse model. MSCs and fRPE cells were transplanted either separately or combined in the subretinal space of retinal degenerative disease animals. ERG, optical coherence tomography, histologic, and immunofluorescence analyses were performed. Furthermore, the expression level of Crx, rhodopsin, Iba1, F4/80, Caspase 3, nerve growth factor, and brain-derived neurotrophic factor were assessed to investigate the mechanisms involved in cell transplantation effects.
方法：通过尾静脉注射碘酸钠（NaIO3）建立视网膜变性的小鼠模型。 将MSCs和fRPE细胞分别或联合移植入视网膜变性动物的视网膜下间隙。 进行了ERG，光学相干断层扫描，组织学和免疫荧光分析。 此外，评估了Crx，视紫红质，Iba1，F4 / 80，半胱天冬酶 3，神经生长因子和脑源性神经营养因子的表达水平，以研究参与细胞移植作用的机制。
Results：Cotransplantation of fRPE and MSC cells promoted significant improvements in ERG results and in the survival rate of transplanted cells. In addition, MSC and fRPE cell cotransplantation resulted in an increase in the thickness of the total retina, as well as in the outer and inner nuclear layers. Combined transplantation also upregulated the expression level of Crx and rhodopsin and downregulated caspase 3 expression, highlighting its better photoreceptor rescue effect in relation to the single cell type transplantation. Finally, combined transplantation suppressed the expression of Iba1 and F4/80 factors while increasing the endogenous expression of nerve growth factor and brain-derived nerve growth factor neurotrophic factors. These data suggest that MSC and fRPE cell cotransplantation is able to suppress immunoreactions and promote neurotrophic factor excretion.
结果：fRPE与MSC联合移植显著提高了ERG的结果和移植细胞的存活率。 此外，MSC和fRPE细胞联合移植后，视网膜总厚度、内外核层厚度均增加。 共同移植还上调了Crx和视紫红质的表达水平，下调了半胱天冬酶 3的表达水平，与单细胞移植相比，联合移植具有更好的感光受体修复作用。 最后，共同移植抑制了Iba1和F4 / 80因子的表达，同时增加了神经生长因子和脑源性神经生长因子神经营养因子的内源性表达。 这些数据表明，MSC和fRPE细胞共同移植能够抑制免疫反应并促进神经营养因子的分泌。
Conclusions：Combined transplantation of MSCs and fRPE cells results in a better retinal rescue effect than single cell type transplantation in NaIO3-induced retinopathy.
结论：在NaIO3诱导的视网膜病变中，MSCs和fRPE细胞的联合移植比单细胞类型的移植具有更好的视网膜修复效果。
推荐理由：
在本研究中，通过尾静脉注射NaIO3成功建立了视网膜变性小鼠模型，将间充质干细胞(MSCs)和人胎视网膜色素上皮细胞(fRPE)分别或共同移植在小鼠模型的视网膜下间隙中，通过ERG，光学相干断层扫描（OCT），组织学和免疫荧光分析以及定量实时PCR（qPCR）。结果证实，经过fRPE和MSC共同移植的小鼠比接受单细胞类型移植的小鼠具有更好的感光受体修复作用。
本研究证明了MSCs和fRPE共同移植的可行性，共同移植可以提高移植细胞存活率，用以代替单细胞类型移植，为干性AMD未来的治疗方案提供了另一条途径。同时还需要进一步的研究来探索fRPE + MSCs共同移植在NaIO3诱导的视网膜病变中修复视网膜细胞的分子机制，包括延长观察时间和鉴定fRPE功能，为以后的临床应用提供更多数据指导。
O——Ophthalmology 推荐
Effificacy and Safety of Suprachoroidal CLSTA for Macular Edema Secondary to Noninfectious Uveitis:Phase 3 Randomized Trial
脉络膜上CLSTA治疗非感染性葡萄膜炎黄斑水肿的有效性和安全性:三期随机试验
Purpose ：Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and effificacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME).
目的：在巩膜和脉络膜之间的脉络膜上间隙注射药物治疗是一种替代性的给药技术，其原理是与其他眼内和眼周注射方法相比，为眼后段结构提供更高的药物浓度。本研究旨在评价脉络膜上注射曲安奈德混悬液（CLS-TA）对非感染性葡萄膜炎合并黄斑水肿（ME）患者视力改善的安全性和有效性。
Design：Phase 3 masked, randomized trial.
设计：3期单盲随机试验。
Participants：One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye.
参与者：160例继发于非感染性葡萄膜炎的ME患者。要求患者的最佳矫正视力（BCVA）为20/800至20/40。换算为早期治疗糖尿病视网膜病变研究（ETDRS）中标准为字母5至70。
Methods：Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12.
方法：患者按3:2的比例随机分为脉络膜上注射CLS-TA组或伪装治疗组，分别在第0天和第12周给药。
Main Outcome Measures：The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfifield thickness (CST) at week 24.
主要观察指标：主要终点是第24周时BCVA中较基线有大于或等于15个ETDRS字母的改善。第二个终点是在第24周时中心亚区厚度（CST）较基线减少。
Results：In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 mm versus 18 mm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively).
结果：在两组中，达到BCVA较基线获得大于等于15个ETDRS字母的主要终点指标的患者在CLS-TA组为47%的，对照组为16%（P<0.001）。与基线检查相比，CST的平均减少值CLS-TA组为153mm，对照组为18mm（P<0.001）。未报告与治疗相关的严重不良事件（AEs）。在CLS-TA组和对照组中，皮质类固醇相关的高眼压不良事件的发生率分别为11.5%和15.6%，白内障不良事件的发生率分别为7.3%和6.3%。
Conclusions：Patients in the CLS-TA study arm experienced clinically signifificant improvement in vision relative to the sham procedure, demonstrating the effificacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.
结论：与对照组相比，CLS-TA研究组的患者在临床上视力有显著改善，证明了脉络膜上注射CLS-TA治疗致盲性黄斑水肿的有效性。
推荐理由：
本文是一篇涉及新型给药技术治疗非感染性葡萄膜炎黄斑水肿的文章，研究设计给药组与对照组，通过定期随访测试患者视力对改善情况进行比较。发现该新型给药技术对比对照组确实有改善视力的作用，对治疗非感染性葡萄膜炎黄斑水肿是有效的。
文章的创新之处为在脉络膜上注射给药，通过脉络膜的一个缓释作用使药物到达眼后段依旧存留一定的有效浓度。该创新技术为其他药物给药方式提供了一种新的思路，避免了直接玻璃体腔注射对人眼自然玻璃体造成干预损伤。
但是该文章依旧存在局限性。首先该方法的对照组患者视力也有部分比例的改善提升，说明给药组的药物作用改善率实际上比统计数据上更低，去除自然改善恢复的概率，约剩31%是由药物作用改善恢复的。改善率很低说明该技术在稳定性方面尚有争议，需在未来做进一步的研究设计。
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