Abstract：
OBJECTIVE: We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD.
METHODS: A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8.
RESULTS: Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).
CONCLUSIONS: Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.
METHODS: A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8.
RESULTS: Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).
CONCLUSIONS: Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.
摘要：
目的：我们以前已经表明，中性粒细胞胞外陷阱（NETs）存在于眼部移植物抗宿主病（oGVHD）患者的眼表，导致炎症和表面疾病。因此,我们使用脱氧核糖核酸酶I(DNAase)滴眼液进行了一项临床试验,以检验减少眼表NETs的丰度将减少oGVHD的体征和症状这一假设.
方法：前瞻性，第一阶段或第二阶段，随机化，安慰剂对照,在oGVHD患者(n=58)中,我们进行了双盲临床试验,以确定DNAase(0.1%)滴眼液每日4次、共8周的安全性和初步疗效.进行意图治疗分析以确定基线和第8周之间安全性结果测量（药物耐受性和不良事件比例）和疗效结果测量（眼表疾病指数[OSDI]评分和角膜染色）的变化。
结果：溶媒组和DNA酶组的耐受性和不良事件相似。在DNA酶组（但不是载体组）内，角膜染色显示,与基线(5.00[3.00;7.00])相比,第8周(3.50[2.75;5.00])有统计学意义和临床意义的减少.在DNA酶组中,与基线(45.5[31.8;50.0])相比,在第8周,OSDI评分还显示出18.4(9.16;33.1)的统计学上有意义的临床意义的降低(P<0.001)。与媒介物组(分别在第4周和第8周的35.7%和34.0%)相比,在DNA酶组中具有主观总体评估(SGA)和粘液排出改善的眼睛的比例(分别在第4周和第8周的55.6%和57.7%;在两个时间点P<0.0001)显著更大。
结论：使用DNAase滴眼液治疗oGVHD患者是安全的，并显示出初步疗效。脱氧核糖核酸酶I滴眼液可能会降低oGVHD患者眼表疾病的体征和症状的严重程度。
方法：前瞻性，第一阶段或第二阶段，随机化，安慰剂对照,在oGVHD患者(n=58)中,我们进行了双盲临床试验,以确定DNAase(0.1%)滴眼液每日4次、共8周的安全性和初步疗效.进行意图治疗分析以确定基线和第8周之间安全性结果测量（药物耐受性和不良事件比例）和疗效结果测量（眼表疾病指数[OSDI]评分和角膜染色）的变化。
结果：溶媒组和DNA酶组的耐受性和不良事件相似。在DNA酶组（但不是载体组）内，角膜染色显示,与基线(5.00[3.00;7.00])相比,第8周(3.50[2.75;5.00])有统计学意义和临床意义的减少.在DNA酶组中,与基线(45.5[31.8;50.0])相比,在第8周,OSDI评分还显示出18.4(9.16;33.1)的统计学上有意义的临床意义的降低(P<0.001)。与媒介物组(分别在第4周和第8周的35.7%和34.0%)相比,在DNA酶组中具有主观总体评估(SGA)和粘液排出改善的眼睛的比例(分别在第4周和第8周的55.6%和57.7%;在两个时间点P<0.0001)显著更大。
结论：使用DNAase滴眼液治疗oGVHD患者是安全的，并显示出初步疗效。脱氧核糖核酸酶I滴眼液可能会降低oGVHD患者眼表疾病的体征和症状的严重程度。
