Rabowsky J H, Dukes A J, Lee D A, Leong K W
Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, School of Medicine 90095-7004, USA.
Ophthalmology. 1996 May;103(5):800-7. doi: 10.1016/s0161-6420(96)30612-x.
Glaucoma filtering surgery usually fails from postoperative fibroblast proliferation, collagen deposition, and subsequent sclerostomy or bleb scarring. Daunorubicin inhibits fibroblast proliferation in vivo and in vitro. The authors studied the effect of a sustained subconjunctival release of daunorubicin by way of a bioerodible polymer on the success of glaucoma filtration surgery in a rabbit model.
Daunorubicin was incorporated into the copolymer by compression molding. The resultant implant measured 3.0 mm in diameter, 1.0 mm in thickness, and 8.0 mg in weight. A posterior lip sclerectomy was performed in both eyes of 23 rabbits by the same surgeon. One eye was randomized to receive the disc with daunorubicin, whereas the fellow eye received a blank disk as a control. The appropriate polymer disk then was placed on the scleral surface immediately posterior to the sclerostomy site and the conjunctiva was closed. Intraocular pressures and slit-lamp biomicroscopy were recorded preoperatively, then every other day after surgery for 31 days. Intraocular pressure, bleb survival, and complications were evaluated.
The decrease in intraocular pressure from baseline was significantly greater in the daunorubicin eyes than in the control eyes during postoperative days 5 through 25. Bleb survival was significantly longer in the daunorubicin eyes than in the control eyes (bleb failure in 91% of control eyes versus 22% of treatment eyes by day 13). There were no statistically significant differences between the daunorubicin-treated and control eyes regarding corneal clouding, lens clarity, cataract formation, or conjunctival injection. However, conjunctival erosions occurred in four daunorubicin-treated eyes. Histopathologic examination was performed 2 weeks after surgery on the eyes of three randomly selected rabbits.
Daunorubicin in a bioerodible delivery system may potentially be a useful adjunct to glaucoma filtering surgery and requires further evaluation.
青光眼滤过手术通常因术后成纤维细胞增殖、胶原沉积以及随后的巩膜造口术或滤过泡瘢痕形成而失败。柔红霉素在体内和体外均可抑制成纤维细胞增殖。作者通过可生物降解聚合物研究了结膜下持续释放柔红霉素对兔青光眼滤过手术成功率的影响。
通过模压将柔红霉素掺入共聚物中。制成的植入物直径3.0毫米,厚度1.0毫米,重量8.0毫克。同一位外科医生对23只兔的双眼进行后唇巩膜切除术。一只眼随机接受含柔红霉素的圆盘,另一只眼接受空白圆盘作为对照。然后将合适的聚合物圆盘立即放置在巩膜造口部位后方的巩膜表面,并关闭结膜。术前记录眼压和裂隙灯生物显微镜检查结果,术后每隔一天记录一次,持续31天。评估眼压、滤过泡存活情况及并发症。
术后第5天至第25天,柔红霉素治疗组眼内压较基线的降低幅度明显大于对照组。柔红霉素治疗组滤过泡存活时间明显长于对照组(至第13天,对照组91%的滤过泡失败,治疗组为22%)。柔红霉素治疗组与对照组在角膜混浊、晶状体清晰度、白内障形成或结膜充血方面无统计学显著差异。然而,柔红霉素治疗组有4只眼出现结膜糜烂。对三只随机选择的兔眼在术后2周进行组织病理学检查。
可生物降解给药系统中的柔红霉素可能是青光眼滤过手术的一种有用辅助手段,需要进一步评估。