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荧光寿命成像眼底镜检查对羟氯喹毒性的成像

Imaging of Hydroxychloroquine Toxicity with Fluorescence Lifetime Imaging Ophthalmoscopy.

作者信息

Sauer Lydia, Calvo Charles M, Vitale Alexandra S, Henrie Nicholas, Milliken Cole M, Bernstein Paul S

机构信息

Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.

Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah; Medical University of South Carolina, Charleston, South Carolina.

出版信息

Ophthalmol Retina. 2019 Oct;3(10):814-825. doi: 10.1016/j.oret.2019.04.025. Epub 2019 May 2.

DOI:10.1016/j.oret.2019.04.025
PMID:31345727
Abstract

PURPOSE

To investigate the impact of retinal toxicity from hydroxychloroquine (HCQ) on fundus autofluorescence lifetimes using fluorescence lifetime imaging ophthalmoscopy (FLIO).

DESIGN

Cross-sectional study.

PARTICIPANTS

Twenty-four eyes of 12 patients with definite HCQ toxicity, 31 eyes of 16 clinically normal patients at high risk of developing HCQ toxicity (taking HCQ longer than 5 years), and 16 eyes of 8 clinically normal patients at low risk of developing HCQ toxicity (taking HCQ fewer than 5 years), as well as 22 age-matched healthy subjects.

METHODS

Fluorescence lifetime images of a 30° retinal field centered at the fovea were collected at the Moran Eye Center, Salt Lake City, Utah. A prototype Heidelberg Engineering Spectralis-based FLIO was used to detect autofluorescence lifetimes in short (SSC; 498-560 nm) and long (LSC; 560-720 nm) spectral channels. Mean fluorescence lifetimes were calculated. OCT scans and macular pigment measures were also recorded. Additionally, the autofluorescence lifetimes of HCQ were measured in a cuvette.

MAIN OUTCOME MEASURES

Mean autofluorescence lifetimes (τ).

RESULTS

All patients with HCQ toxicity showed significantly prolonged FLIO lifetimes in regions of damage, typically in a bulls-eye distribution corresponding to toxic lesions in the retina (SSC: lesion, 400 ps; unremarkable retina, 294 ps; P < 0.001; LSC: lesion, 404 ps; unremarkable retina, 316 ps; P < 0.001). Some clinically normal patients at high risk (9 of 16) and at low risk (2 of 8) of developing HCQ toxicity also showed prolonged FLIO lifetimes in the parafoveal region, whereas age-matched healthy subjects did not. HCQ at a concentration of 46 mM exhibited long autofluorescence lifetimes of around 1100 ps in either spectral channel.

CONCLUSIONS

Fluorescence lifetime imaging ophthalmoscopy seems to detect retinal toxicity from HCQ at very early stages and could be a novel method to detect retinal toxicity before irreversible damage is manifest.

摘要

目的

使用荧光寿命成像检眼镜(FLIO)研究羟氯喹(HCQ)引起的视网膜毒性对眼底自发荧光寿命的影响。

设计

横断面研究。

参与者

12例确诊为HCQ毒性患者的24只眼、16例有发生HCQ毒性高风险的临床正常患者(服用HCQ超过5年)的31只眼、8例有发生HCQ毒性低风险的临床正常患者(服用HCQ少于5年)的16只眼,以及22例年龄匹配的健康受试者。

方法

在犹他州盐湖城的莫兰眼科中心采集以黄斑中心凹为中心的30°视网膜区域的荧光寿命图像。使用基于海德堡工程公司Spectralis的FLIO原型在短(SSC;498 - 560 nm)和长(LSC;560 - 720 nm)光谱通道中检测自发荧光寿命。计算平均荧光寿命。还记录了光学相干断层扫描(OCT)扫描和黄斑色素测量结果。此外,在比色皿中测量了HCQ的自发荧光寿命。

主要观察指标

平均自发荧光寿命(τ)。

结果

所有HCQ毒性患者在损伤区域均表现出FLIO寿命显著延长,通常呈靶心分布,对应于视网膜毒性病变(SSC:病变区域,400 ps;视网膜正常区域,294 ps;P < 0.001;LSC:病变区域,404 ps;视网膜正常区域,316 ps;P < 0.001)。一些有发生HCQ毒性高风险(16例中的9例)和低风险(8例中的2例)的临床正常患者在黄斑旁区域也表现出FLIO寿命延长,而年龄匹配的健康受试者则未出现这种情况。浓度为46 mM的HCQ在任一光谱通道中均表现出约1100 ps的长自发荧光寿命。

结论

荧光寿命成像检眼镜似乎能在非常早期阶段检测到HCQ引起的视网膜毒性,并且可能是在不可逆损伤出现之前检测视网膜毒性的一种新方法。

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