Unit on Neuron–Glia Interactions in Retinal Disease, Building 6, Room 215, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Invest Ophthalmol Vis Sci. 2013 Apr 26;54(4):2941-50. doi: 10.1167/iovs.13-11650.
To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA).
The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area.
The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months.
Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).
研究 mTOR 抑制剂和免疫抑制剂丝裂霉素（sirolimus）经结膜下给药治疗地图状萎缩（GA）的安全性和效果。
本研究为单中心、开放性、二期临床试验，共纳入 11 名双眼均患有 GA 的患者；其中 8 名患者完成了 24 个月的随访。在每位患者中，随机选择一只眼接受每 3 个月一次的结膜下注射（440μg），连续注射 24 个月；对侧眼作为未治疗的对照。主要疗效评估指标为 24 个月时总 GA 面积的变化。次要终点包括视力、黄斑敏感性、中心视网膜厚度和总玻璃膜疣面积的变化。
研究药物具有良好的耐受性，仅有少数症状和相关不良反应。与对侧未治疗的对照眼相比，研究眼的治疗并未带来结构或功能上的获益。在 24 个月时，研究眼和对照眼的 GA 面积分别增加了 54.5%和 39.7%（P = 0.41），而研究眼和对照眼的平均视力分别下降了 21.0 个字母和 3.0 个字母（P = 0.03）。在 24 个月内的所有分析时间点，研究眼和对照眼的平均玻璃膜疣面积、中央视网膜厚度和黄斑敏感性变化差异均无统计学意义。
重复经结膜下给予丝裂霉素治疗 GA 患者具有良好的耐受性，尽管未发现阳性的解剖或功能效果。结膜下给予丝裂霉素可能无益于预防 GA 进展，并且可能对视敏度产生潜在的不利影响。（临床试验注册号：NCT00766649.）
