Pilot Study to Evaluate Oral Minocycline in the Treatment of Cystoid Macular Edema Associated with Retinitis Pigmentosa

黄斑囊样水肿（CME）是视网膜色素变性（RP）的常见特征，影响多达1/3的患者。 RP相关的CME与视网膜神经炎症和小胶质细胞活化有关。 米诺环素是FDA批准的抗生素，对小胶质细胞活化发挥标签外抑制作用，并减少炎症因子的产生，已发现在RP动物模型中发挥神经保护作用。 本研究的目的是探讨口服米诺环素作为RP患者CME的主要治疗方法的安全性和可能的疗效。 一项单中心、前瞻性、开放标签的I/II期临床试验招募了5名患有与RP相关的双侧CME的受试者。 每名参与者的一只眼睛被指定为研究眼睛，对侧眼睛被指定为对侧眼睛。参与者每月随访3个月，然后口服米诺环素100 mg，每天两次，持续12个月。 主要结局变量包括：（1）最佳矫正视力（BCVA）的变化和（2）使用光谱域光学相干断层扫描（SD-OCT）测量的视网膜中央子场厚度（CST）相对于治疗前平均测量值的变化。 研究药物耐受性良好，与任何重大不良事件无关。 在研究眼或对侧眼中均未观察到平均BCVA的显著变化（所有比较均为P>0.05）。 所有眼睛相对于基线的变化<10个字母。 然而，CST的平均百分比变化随着治疗时间的推移而逐渐降低。 考虑到所有眼睛（n = 10），CST分别在6个月和12个月时降低（p=0.63）和（p=0.03）。 米诺环素给药超过12个月与以下因素相关： 黄斑中心平均厚度小幅但进行性显著降低。 平均视力无显著变化 平均微视野反应无显著变化。 米诺环素是否是RP黄斑水肿的潜在有效干预方式，还需要进一步研究。

Cystoid macular edema (CME) is a common feature in retinitis pigmentosa (RP), affecting up to 1/3 of patients. RP-associated CME has been related to retinal neuroinflammation and microglial activation. Minocycline, a FDA-approved antibiotic, exerts off-label inhibition of microglial activation and decreases inflammatory factor production, and has been found to exert neuroprotection in RP animal models. The objective of this study is to investigate the safety and possible efficacy of oral minocycline as a primary treatment for CME in RP. A single-center, prospective, open-label Phase I/II clinical trial enrolled five participants with bilateral CME associated with RP. One eye in each participant was assigned as the study eye and the contralateral eye as the fellow eye. Participants were followed monthly for 3 months off-drug and then administered oral minocycline 100 mg twice daily for 12 months. Main outcome variables included:(1) changes in best corrected visual acuity (BCVA) and (2) changes in retinal central subfield thickness (CST) measured using spectral domain optical coherence tomography (SD-OCT) relative to mean pretreatment measurements. The study drug was well tolerated and not associated with any significant adverse events. No significant changes in mean BCVA were noted in either the study eye or the fellow eye (P>0.05 for all comparisons). Changes relative to baseline were <10 letters for all eyes. Mean percentage changes in CST however decreased progressively with time on treatment. Considering all eyes (n = 10), a decrease in CST decrease at 6 and 12 months (p=0.63) and (p=0.03) respectively. Minocycline administration over 12 months was associated with: A small but progressive and significant decrease in mean central macular thickness. No significant changes in mean visual acuity No significant change in average microperimetry responses. Further study is needed to determine whether minocycline is a potentially useful mode of intervention for macular edema in the setting of RP.