Evaluation of Sirolimus in the Treatment of Diabetic Macular Edema

这项研究将测试西罗莫司是否能帮助糖尿病黄斑水肿患者。黄斑是视网膜中负责精细视力的区域，由于糖尿病可能会导致水肿症，导致视力丧失。西罗莫司抑制体内一种名为mTOR的蛋白质，这种蛋白质在调节细胞分裂和生长方面发挥着关键作用。西罗莫司也被认为影响炎症过程。出于这两个原因，该药物可能有助于治疗糖尿病黄斑水肿。 这项研究是一项对5名患有糖尿病黄斑水肿的参与者进行的开放式先导性研究。在研究眼在基线和2个月接受20 L(440g)结膜下注射后，参与者将在至少一年的时间里每两个月重新评估可能的额外注射。在随访期间，如果参与者的临床表现有显著改善或治疗成功，则不会再次注射，其定义是光学相干断层扫描(OCT)没有视网膜内液体或囊肿，或OCT时视网膜过度厚度减少100%超过260微米，或荧光素血管成像(FA)没有渗漏。从第4个月开始，参与者将接受治疗失败的评估，定义为连续两次就诊时视力较基线下降15个或更多，或连续两次OCT测量的视网膜总厚度增加50%或更多。被认为治疗失败的个体参与者将继续接受西罗莫司注射，但将被允许在4个月时接受任何顺应性渗漏微动脉瘤的局部激光治疗。从6个月开始，治疗失败和不符合治疗成功标准的参与者都将被允许进行局部激光治疗。参与者将可以选择继续治疗，直到通常的终止日期为一年。 主要结果是研究眼在6个月时的视力与基线相比的变化。次要结果包括研究眼一年的视力与基线相比的变化，OCT测量的视网膜厚度的变化，以及在研究的六个月、一年和整个研究期间以及研究中的其他眼睛的FA所显示的黄斑液体渗漏的变化。安全性结果包括全身和眼部毒性、不良事件和感染的数量和严重程度，以及退出研究治疗的参与者数量。

This study will test whether sirolimus can help patients with diabetic macular edema. The macula, the area of the retina that is responsible for fine vision, can become edematous due to diabetes and result in visual loss. Sirolimus inhibits a protein in the body called mTOR, which plays a critical role in regulating how cells divide and grow. Sirolimus is also believed to affect the inflammatory process. For both these reasons, the drug may be helpful in treating diabetic macular edema. This study is an open label pilot study of five participants with diabetic macular edema. After receiving a 20 L (440 g) subconjunctival injection in the study eye at baseline and Month 2, the participants will be re-evaluated every two months for at least one year for possible additional injections. During follow-up, participants will not undergo re-injection if they show significant clinical improvement or treatment success, defined as no intraretinal fluid or cysts present on optical coherence tomography (OCT) OR 100% reduction in excess retinal thickness over 260 microns on OCT OR no leakage on fluorescein angiography (FA). Beginning at Month 4, participants will be assessed for treatment failure, defined as loss of 15 or more letters of vision compared to baseline at two consecutive visits OR a 50% or greater increase in total retinal thickness as measured by OCT at two consecutive visits. Individual participants deemed treatment failures will continue receiving sirolimus injections, but will be allowed to receive focal laser therapy for any amenable leaking microaneurysms at Month 4. Beginning at Month 6, focal laser therapy will be permitted for both treatment failures and participants who do not meet the criteria of a treatment success. Participants will have the option of continuing treatment until a common termination date of one year. The primary outcome is the change in visual acuity in the study eye at six months compared to baseline. Secondary outcomes include changes in visual acuity in the study eye at one year as compared with baseline, changes in retinal thickness as measured by OCT and changes in fluid leakage in the macula as demonstrated by FA at six months, one year and throughout the study period in the study and fellow eyes. Safety outcomes include number and severity of systemic and ocular toxicities, adverse events and infections, and the number of participants withdrawn from study therapy.