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玻璃体内注射西多福韦(HPMPC)治疗获得性免疫缺陷综合征患者的巨细胞病毒性视网膜炎。

Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.

作者信息

Kirsch L S, Arevalo J F, Chavez de la Paz E, Munguia D, de Clercq E, Freeman W R

机构信息

Department of Ophthalmology, Shiley Eye Center, University of California at San Diego, La Jolla 92093-0946, USA.

出版信息

Ophthalmology. 1995 Apr;102(4):533-42; discussion 542-3. doi: 10.1016/s0161-6420(95)30985-2.

Abstract

PURPOSE

The authors previously conducted a pilot, dose-escalating study which suggested that a 20-micrograms dose of intravitreal cidofovir (HPMPC) may be safe and effective in treating cytomegalovirus (CMV) retinitis in humans. The purpose of this series is to expand the authors' prior experience with the 20-micrograms dose of cidofovir as the sole treatment for CMV retinitis in patients with acquired immune deficiency syndrome.

METHODS

The study design was an unmasked consecutive case series trial in a single-center institutional retina referral practice. Eligible patients with acquired immune deficiency syndrome had active CMV retinitis in at least one eye and no evidence of extraocular CMV disease. Patients received a 20-micrograms cidofovir trans pars plana injection and were treated with concomitant oral probenecid. Retreatments were performed for progression of retinitis as determined by serial fundus photographs judged independently by three observers. The primary outcome was time to retinitis progression determined by Kaplan-Meier analysis. Both globes of one patient who had unilateral retinitis were examined pathologically.

RESULTS

There were 37 cidofovir injections in 24 eyes of 17 patients. The median time to retinitis progression after the initial 24 injections was 55 days. The median time to retinitis progression after 8 repeat cidofovir injections was 63 days. There was a significant decrease in intraocular pressure from baseline to both 2 and 4 weeks after injection. A mild to moderate iritis developed in five (20.8%) eyes that responded well to topical medications. Results of histopathologic examination of one treated globe did not show any significant toxic effects.

CONCLUSIONS

This study demonstrates that prolonged arrest of the progression of CMV retinitis may be obtained with a single 20-micrograms cidofovir intravitreal injection. In addition, the effect of the drug appears to be maintained after a second injection. The effects of cidofovir in causing uveitis and a slight lowering of the intraocular pressure require further study.

摘要

目的

作者之前进行了一项剂量递增的初步研究,结果表明玻璃体内注射20微克西多福韦(HPMPC)治疗人类巨细胞病毒(CMV)视网膜炎可能安全有效。本系列研究的目的是扩展作者之前使用20微克剂量西多福韦作为获得性免疫缺陷综合征患者CMV视网膜炎唯一治疗方法的经验。

方法

本研究设计为单中心机构视网膜转诊实践中的非盲连续病例系列试验。符合条件的获得性免疫缺陷综合征患者至少一只眼睛患有活动性CMV视网膜炎,且无眼外CMV疾病证据。患者接受20微克西多福韦经平坦部玻璃体注射,并同时口服丙磺舒进行治疗。根据由三名观察者独立判断的系列眼底照片确定视网膜炎进展情况,对视网膜炎进展的患者进行再次治疗。主要结局是通过Kaplan-Meier分析确定的视网膜炎进展时间。对一名单侧视网膜炎患者的双眼进行了病理检查。

结果

17例患者的24只眼中共进行了37次西多福韦注射。最初24次注射后视网膜炎进展的中位时间为55天。8次重复西多福韦注射后视网膜炎进展的中位时间为63天。注射后2周和4周时,眼压较基线均有显著下降。5只眼(20.8%)出现轻度至中度虹膜炎,局部用药反应良好。对一只治疗眼的组织病理学检查结果未显示任何明显的毒性作用。

结论

本研究表明,单次玻璃体内注射20微克西多福韦可使CMV视网膜炎进展得到长期抑制。此外,第二次注射后药物效果似乎得以维持。西多福韦引起葡萄膜炎和眼压略有降低的作用需要进一步研究。

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