Sheu Shwu-Jiuan, Bee Youn-Shen, Lin Hsiu-Chen, Ho Wan-Ling, Wu Tsung-Tien
Department of Ophthalmology, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
J Chin Med Assoc. 2008 Mar;71(3):135-42. doi: 10.1016/S1726-4901(08)70005-4.
Current photodynamic therapy (PDT) for choroidal neovascularization (CNV) uses a standard radiant exposure of 50 J/cm2 at an irradiance of 600 mW/cm2. However, low-intensity PDT with verteporfin for neovascular tissue has been shown to be more effective than regular high-intensity PDT in an animal model of healthy choroids and corneal neovascularization. Low-intensity PDT also supposedly induces less retinal damage. In this study, we compared the effect of reduced-dose and standard light application PDT in an animal model of CNV.
A laser injury model was used to induce CNV 3 weeks prior to PDT in brown Norway rats. The CNV lesions were then treated with verteporfin PDT with a dose of verteporfin 6.0 mg/m2 and 5 activating doses of light energy (43, 53, 63, 73 and 83 seconds). Closure of CNV was assessed by fundus fluorescein angiography (FAG). Histopathologic study was done after the last FAG.
PDT with verteporfin significantly reduced the CNV area compared with control non-treated groups 1 week after PDT (p < 0.05). Only those lesions treated for 63 seconds or longer retained their significantly attenuating effect on CNV up to 3 weeks after PDT. There was no significant difference between the inhibition effects induced by reduced-intensity light application for 63 or 73 seconds compared to the standard radiant exposure (83 seconds). Histopathologic study showed that eyes treated with PDT showed significantly less extent and vascularity of CNV lesion than control lesions.
Reduced-intensity PDT with 63-second duration seemed to be as effective as standard dose for CNV suppression. Considering the possible retinal damage following standard PDT, the PDT dose might be adjusted to reduce side effects. Further preclinical study will provide more data on what constitutes appropriate dosimetry for effective and safe PDT in CNV.
目前用于脉络膜新生血管（CNV）的光动力疗法（PDT）采用标准辐射暴露剂量50 J/cm²，辐照度为600 mW/cm²。然而，在健康脉络膜和角膜新生血管的动物模型中，用维替泊芬进行的低强度PDT对新生血管组织已显示出比常规高强度PDT更有效。低强度PDT据推测还能减少视网膜损伤。在本研究中，我们比较了降低剂量和标准光照射PDT在CNV动物模型中的效果。
在棕色挪威大鼠中，于PDT前3周使用激光损伤模型诱导CNV。然后用维替泊芬PDT治疗CNV病变，维替泊芬剂量为6.0 mg/m²，并用5个激活光能剂量（43、53、63、73和83秒）。通过眼底荧光血管造影（FAG）评估CNV的闭合情况。在最后一次FAG后进行组织病理学研究。
与未治疗的对照组相比，PDT后1周，维替泊芬PDT显著减小了CNV面积（p < 0.05）。只有那些接受63秒或更长时间治疗的病变在PDT后3周仍对CNV保持显著的减弱作用。与标准辐射暴露（83秒）相比，63秒或73秒的低强度光照射诱导的抑制效果之间没有显著差异。组织病理学研究表明，接受PDT治疗的眼睛CNV病变的范围和血管化程度明显低于对照病变。
持续63秒的低强度PDT在抑制CNV方面似乎与标准剂量一样有效。考虑到标准PDT后可能出现的视网膜损伤，可调整PDT剂量以减少副作用。进一步的临床前研究将提供更多数据，以确定在CNV中有效且安全的PDT的合适剂量。
