Tzekov Radouil, Lin Ton, Zhang Kai-Ming, Jackson Brittany, Oyejide Adelekan, Orilla Werhner, Kulkarni Amol D, Kuppermann Baruch D, Wheeler Larry, Burke James
Department of Biological Sciences, Allergan Inc., Irvine, California 92612, USA.
Invest Ophthalmol Vis Sci. 2006 Jan;47(1):377-85. doi: 10.1167/iovs.05-0838.
The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina.
As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In addition, retinal histopathologic findings were evaluated at 9 months.
Various morphologic changes, including whitening of the treated area, RPE proliferation, closure of the choroidal vasculature, and subretinal edema (followed by foveolar thinning) were observed. Most of the changes persisted and were detectable in histopathologic evaluation at 9 months. Reductions of the mfERG amplitude, followed by varying degrees of recovery from the treated and the border regions, were observed. This was accompanied by progressive delay of P1 peak time up to 3 months after treatment, followed by complete recovery at 9 months. In addition, the nontreated area showed amplitude and timing mfERG deficits, which underwent gradual (but not complete) recovery.
In a primate model, under standard clinical parameters, a single PDT treatment resulted in various dynamic morphologic and functional retinal changes detectable for up to 9 months after treatment. The significance of the observed changes and possible ways of pharmacologic interference with PDT adverse effects are discussed.
本研究的目的是确定在完整的非人灵长类动物视网膜单次光动力疗法(PDT)后灵长类视觉系统的变化。
作为一项更大规模研究的一部分,对两只食蟹猴的每只眼睛进行了使用维替泊芬(6 mg/m²静脉输注)的PDT(波长689 nm,50 J/cm²,600 mW/cm²,83秒,光斑大小4 mm)。在基线以及PDT后的12个时间点(1 - 283天)进行了眼底摄影、荧光素血管造影(FA)、吲哚菁绿血管造影(ICG)、光学相干断层扫描(OCT)和多焦视网膜电图(mfERG)检查。此外,在9个月时评估了视网膜组织病理学结果。
观察到各种形态学变化,包括治疗区域变白、视网膜色素上皮(RPE)增殖、脉络膜血管系统闭合以及视网膜下水肿(随后黄斑变薄)。大多数变化持续存在,并在9个月时的组织病理学评估中可检测到。观察到mfERG振幅降低,随后在治疗区域和边缘区域有不同程度的恢复。这伴随着治疗后长达3个月的P1峰时间逐渐延迟,随后在9个月时完全恢复。此外,未治疗区域显示出mfERG振幅和时间缺陷,这些缺陷逐渐(但未完全)恢复。
在灵长类动物模型中,在标准临床参数下,单次PDT治疗导致了多种动态的视网膜形态和功能变化,在治疗后长达9个月均可检测到。讨论了观察到的变化的意义以及对PDT不良反应进行药物干预的可能方法。