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在兔角膜新生血管模型中使用维替泊芬进行光动力疗法。

Photodynamic therapy with verteporfin in a rabbit model of corneal neovascularization.

作者信息

Holzer Mike P, Solomon Kerry D, Vroman David T, Sandoval Helga P, Margaron Philippe, Kasper Terrance J, Crosson Craig E

机构信息

Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

出版信息

Invest Ophthalmol Vis Sci. 2003 Jul;44(7):2954-8. doi: 10.1167/iovs.02-0572.

DOI:10.1167/iovs.02-0572
PMID:12824237
Abstract

PURPOSE

To determine the efficacy of photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) for treatment of corneal neovascularization in a rabbit eye model.

METHODS

Corneal neovascularization was induced in Dutch belted rabbits by placing an intrastromal silk suture near the limbus. Verteporfin was administered by intravenous injection at a dose of 1.5 mg/kg, and the pharmacokinetics of verteporfin distribution in the anterior segment or PDT-induced (laser energy levels 17, 50, and 150 J/cm(2)) regression of corneal blood vessels were then determined. To assess PDT-induced toxicity of the anterior segment, corneal and iris/ciliary body histology, and IOP were evaluated after PDT.

RESULTS

Verteporfin accumulation in vascularized regions of the cornea and the iris/ciliary body tissue were time dependent and maximum levels achieved at 60 minutes after injection. In rabbits, PDT of corneal vessels using laser energy of 17 or 50 J/cm(2) resulted in 30% to 50% regression of corneal neovascularization; however, in these animals, a rapid regrowth of new blood vessels occurred between 3 and 5 days. In the rabbits receiving PDT using laser energies of 150 J/cm(2), the mean vessel regression was 56%. During the nine days of the laser therapy follow-up period, no vessel regrowth was observed in these rabbits. Histologic examination of the anterior segment after PDT (150 J/cm(2)) showed localized degeneration of the corneal blood vessels without observable change in other anterior segment structures.

CONCLUSIONS

These results provide evidence that PDT can produce significant regression of neovascular corneal vessels with no observable toxicity to the anterior segments. However, the optimal laser energy necessary to induce long-term regression (150 J/cm(2)) was three times that used to treat choroidal neovascularization.

摘要

目的

在兔眼模型中确定维替泊芬(Visudyne;诺华公司,瑞士巴塞尔)光动力疗法(PDT)治疗角膜新生血管的疗效。

方法

通过在荷兰带兔角膜缘附近基质内植入丝线诱导角膜新生血管形成。静脉注射维替泊芬,剂量为1.5 mg/kg,然后测定维替泊芬在前房的药代动力学分布或PDT诱导(激光能量水平分别为17、50和150 J/cm²)的角膜血管消退情况。为评估PDT对眼前段的毒性,在PDT后评估角膜和虹膜/睫状体组织学以及眼压。

结果

维替泊芬在角膜血管化区域和虹膜/睫状体组织中的蓄积呈时间依赖性,注射后60分钟达到最高水平。在兔中,使用17或50 J/cm²激光能量进行角膜血管的PDT可使角膜新生血管消退30%至50%;然而,在这些动物中,3至5天内新血管迅速再生。在接受150 J/cm²激光能量PDT的兔中,平均血管消退率为56%。在激光治疗随访的9天期间,这些兔未观察到血管再生。PDT(150 J/cm²)后眼前段组织学检查显示角膜血管局部变性,其他眼前段结构未观察到变化。

结论

这些结果表明,PDT可使角膜新生血管显著消退,且对眼前段无明显毒性。然而,诱导长期消退所需的最佳激光能量(150 J/cm²)是治疗脉络膜新生血管所用能量的三倍。

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