Kramer M, Miller J W, Michaud N, Moulton R S, Hasan T, Flotte T J, Gragoudas E S
Laser Research Laboratory, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, 02114, USA.
Ophthalmology. 1996 Mar;103(3):427-38. doi: 10.1016/s0161-6420(96)30675-1.
The authors have previously shown that photodynamic therapy (PDT) using lipoprotein-delivered benzoporphyrin derivative mono-acid (BPD) effectively closed experimental choroidal neovascularization (CNV). In the current study, the authors used a clinical preparation, liposomal BPD verteporfin in the same model, with experiments designed to establish optimal dye and light doses, and the timing of laser light irradiation after dye injection, for effective and selective closure of CNV.
Experimental CNV was induced in the maculae of cynomolgus monkeys. Liposomal BPD verteporfin was injected intravenously at doses of 1.0, 0.5, 0.375, and 0.25 mg/kg. Laser light at 692 nm then was applied to CNV, with an irradiance of 600 mW/cm2 and fluence of 150 J/cm2, at various times after dye injection, ranging from 5 to 120 minutes. Treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by light and electron microscopy. The PDT of experimental CNV was studied to assess efficacy; PDT performance on normal eyes was studied to investigate selectivity.
The CNV closure was demonstrated by fluorescein angiography and histopathologic findings at all tested dye doses. A dye dose of 0.375 mg/kg, with laser light irradiation applied 20 to 50 minutes after dye injection, optimized CNV closure with minimal retinal and choroidal damage. No major local adverse effects were noted, and the drug was well tolerated systematically.
Liposomal BPD verteporfin is a potent photosensitizer, and PDT using this dye is a potentially effective and selective treatment for CNV.
作者先前已表明，使用脂蛋白递送的苯并卟啉衍生物单酸（BPD）进行光动力疗法（PDT）可有效封闭实验性脉络膜新生血管（CNV）。在本研究中，作者在同一模型中使用了一种临床制剂——脂质体BPD维替泊芬，设计实验以确定最佳染料和光剂量，以及染料注射后激光照射的时间，从而有效且选择性地封闭CNV。
在食蟹猴的黄斑区诱导实验性CNV。以1.0、0.5、0.375和0.25mg/kg的剂量静脉注射脂质体BPD维替泊芬。然后在染料注射后的不同时间（5至120分钟），对CNV施加692nm的激光，辐照度为600mW/cm²，能量密度为150J/cm²。通过眼底照相和荧光素血管造影评估治疗效果，并通过光镜和电镜进行确认。研究实验性CNV的PDT以评估疗效；研究PDT对正常眼睛的作用以研究其选择性。
在所有测试的染料剂量下，荧光素血管造影和组织病理学结果均显示CNV封闭。0.375mg/kg的染料剂量，在染料注射后20至50分钟进行激光照射，可在对视网膜和脉络膜损伤最小的情况下优化CNV封闭。未观察到重大局部不良反应，该药物在全身耐受性良好。
脂质体BPD维替泊芬是一种有效的光敏剂，使用这种染料的PDT对CNV是一种潜在有效的选择性治疗方法。
