Department of Ophthalmology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium.
N Engl J Med. 2012 Aug 16;367(7):606-15. doi: 10.1056/NEJMoa1110823.
Vitreomacular adhesion can lead to pathologic traction and macular hole. The standard treatment for severe, symptomatic vitreomacular adhesion is vitrectomy. Ocriplasmin is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface.
We conducted two multicenter, randomized, double-blind, phase 3 clinical trials to compare a single intravitreal injection of ocriplasmin (125 μg) with a placebo injection in patients with symptomatic vitreomacular adhesion. The primary end point was resolution of vitreomacular adhesion at day 28. Secondary end points were total posterior vitreous detachment and nonsurgical closure of a macular hole at 28 days, avoidance of vitrectomy, and change in best-corrected visual acuity.
Overall, 652 eyes were treated: 464 with ocriplasmin and 188 with placebo. Vitreomacular adhesion resolved in 26.5% of ocriplasmin-injected eyes and in 10.1% of placebo-injected eyes (P<0.001). Total posterior vitreous detachment was more prevalent among the eyes treated with ocriplasmin than among those injected with placebo (13.4% vs. 3.7%, P<0.001). Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo-injected eyes (P<0.001). The best-corrected visual acuity was more likely to improve by a gain of at least three lines on the eye chart with ocriplasmin than with placebo. Ocular adverse events (e.g., vitreous floaters, photopsia, or injection-related eye pain--all self-reported--or conjunctival hemorrhage) occurred in 68.4% of ocriplasmin-injected eyes and in 53.5% of placebo-injected eyes (P<0.001), and the incidence of serious ocular adverse events was similar in the two groups (P=0.26).
Intravitreal injection of the vitreolytic agent ocriplasmin resolved vitreomacular traction and closed macular holes in significantly more patients than did injection of placebo and was associated with a higher incidence of ocular adverse events, which were mainly transient. (Funded by ThromboGenics; ClinicalTrials.gov numbers, NCT00781859 and NCT00798317.).
玻璃体黄斑粘连可导致病理性牵引和黄斑裂孔。严重、有症状的玻璃体黄斑粘连的标准治疗方法是玻璃体切除术。Ocrliprasin 是一种具有纤连蛋白和层粘连蛋白活性的重组蛋白酶,而这两种蛋白都是玻璃体视网膜界面的组成部分。
我们进行了两项多中心、随机、双盲、3 期临床试验,比较了玻璃体腔注射 125μg Ocrliprasin 与安慰剂治疗有症状的玻璃体黄斑粘连患者的效果。主要终点是第 28 天玻璃体黄斑粘连的缓解情况。次要终点是 28 天总玻璃体后脱离和黄斑裂孔的非手术闭合、避免玻璃体切除术以及最佳矫正视力的变化。
共有 652 只眼接受了治疗:464 只眼接受 Ocrliprasin 治疗,188 只眼接受安慰剂治疗。玻璃体黄斑粘连在 Ocrliprasin 治疗的眼中缓解率为 26.5%,安慰剂治疗的眼中为 10.1%(P<0.001)。玻璃体后脱离在接受 Ocrliprasin 治疗的眼中更为常见(13.4%比 3.7%,P<0.001)。黄斑裂孔的非手术闭合在接受 Ocrliprasin 治疗的眼中的发生率为 40.6%,安慰剂治疗的眼中为 10.6%(P<0.001)。用 Ocrliprasin 治疗的眼中至少提高了三个视标字母的最佳矫正视力的可能性大于用安慰剂治疗的眼中(P<0.001)。眼部不良事件(如玻璃体漂浮物、闪光感或与注射相关的眼痛-均为自我报告-或结膜出血)在接受 Ocrliprasin 治疗的眼中的发生率为 68.4%,在接受安慰剂治疗的眼中为 53.5%(P<0.001),两组严重眼部不良事件的发生率相似(P=0.26)。
与安慰剂相比,玻璃体腔内注射玻璃体分解剂 Ocrliprasin 显著增加了玻璃体黄斑牵引缓解和黄斑裂孔闭合的患者比例,且与更高的眼部不良事件发生率相关,这些不良事件主要是短暂的。(由 ThromboGenics 资助;临床试验.gov 编号,NCT00781859 和 NCT00798317)。