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The Future of Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) in Clinical Care

使用唯一的成像模式,其类型在美国.S., Moran physician-scientists are working to revolutionize how clinicians diagnose and treat diseases.

Moran的Lydia Sauer博士和保罗年代. 伯恩斯坦,医学博士,博士, work with a cutting-edge, non-invasive imaging tool known as FLIO.
Moran的Lydia Sauer博士和保罗年代. 伯恩斯坦,医学博士,博士, work with a cutting-edge, non-invasive imaging tool known as FLIO.

 

By Lydia Sauer, MD; and 保罗年代. 伯恩斯坦,医学博士,博士

人眼成像长期以来一直指导着临床护理, helping ophthalmologists better understand and diagnose pathologies and diseases of the eye.

The retina was first viewed in living patients by German physician and physicist Hermann von Helmholtz in 1851, 谁用眼底镜检查眼睛的内部. Since then, beginning with delicate hand drawings, a variety of modalities have been developed. 从眼底摄影到先进的成像技术, they all give detailed information on the microstructure of the human eye.

常用的技术是光学相干层析成像, which investigates the reflectance of different layers within the eye, 以及基于荧光的成像模式, 它们给出了眼睛中分子的信息. 眼睛里的荧光分子, 被称为荧光团, 能不同程度地吸收和发射光吗. Some fluorophores absorb more light; these appear dark on images. Other fluorophores absorb less light; these appear bright on images.

哈佛科学家弗朗索瓦C. Delori and coworkers spent considerable effort describing the fluorescence of the human retina and established how fluorophores are altered in diseases. The strongest fluorescence is emitted from lipofuscin, the dominant fluorophore within the retina.1 Accumulation of lipofuscin and other strongly fluorescent fluorophores can be seen in diseases such as age-related macular degeneration. 整体, 荧光团的变化导致光信号的改变, 哪些是从眼睛发出的, 随后, ophthalmologists can detect these as disease-related changes.

FLIO图片
These fluorescence lifetime imaging ophthalmoscopy (FLIO) images show a family with MacTel. 最小的兄弟姐妹(左), 男性, 22,)显示了先进的MacTel, 用蓝色中心标出疾病. 一个孩子, 尽管临床检查结果正常, 还显示了表明MacTel(中)的FLIO变化, 女, 26), whereas the other sibling has a completely healthy FLIO (right, 女, 28). FLIO has been shown to be effective in detecting early stages of MacTel before retinal damage has occurred.

The Possibility of Detecting Eye Diseases Earlier Than Ever Before

A promising but not yet widely established fluorescence-based imaging method is fluorescence lifetime imaging ophthalmoscopy (FLIO), which was invented by German scientist Dietrich Schweitzer and coworkers in 2002.2

与传统的荧光成像相比, FLIO研究了荧光的另一种特性, 荧光寿命. 这个参数告诉大发娱乐荧光团发光的时间, which is independent of the strength of the individual fluorescence. Fluorophores that emit only weak amounts of light can be detected with this novel method.3

因为有些疾病从很小的变化开始, conventional fluorescence imaging may not always detect these tiny changes. FLIO, however, can do so, making it helpful in the early detection of diseases. It also helps to understand how eye diseases will progress over time.

A variety of retinal diseases have been investigated with FLIO, and many studies showed the advantages of FLIO technology over other imaging modalities.4, 5 莫兰眼科中心的FLIO, a prototype manufactured by Heidelberg Engineering in Germany, 是美国唯一的同类设备.

These fluorescence lifetime imaging ophthalmoscopy (FLIO) images show a family with MacTel. 最小的兄弟姐妹(左), 男性, 22,)显示了先进的MacTel, 用蓝色中心标出疾病. 一个孩子, 尽管临床检查结果正常, 还显示了表明MacTel(中)的FLIO变化, 女, 26), whereas the other sibling has a completely healthy FLIO (right, 女, 28). FLIO has been shown to be effective in detecting early stages of MacTel before retinal damage has occurred.

One interesting example of the advantages of FLIO relates to an inherited macular dystrophy called macular telangiectasia type 2 (MacTel). 最初, MacTel被认为是一种罕见的疾病, but recent studies argue for a much higher prevalence than initially assumed.6 Early clinical trials of an implant that is aimed to stop disease progression showed promising results, 这意味着治疗 因为这种疾病可能很快就会出现. 它是, 因此, crucial to correctly diagnose this disease at an early stage for the success of the treatment.7 许多发现导致了MacTel的诊断, 比如视网膜囊肿, para-foveal晶体, 甚至是低黄斑色素值, 在疾病的早期阶段会缺席吗.

There is a need for a reliable imaging modality that can detect changes at early stages. 大发娱乐的研究表明FLIO是一个很好的选择.8Not only can FLIO detect retinal changes in MacTel once the disease has manifested, but FLIO has also been shown to detect alterations in individuals before typical retinal damages occur.9举个例子, 大发娱乐调查了一个有三个兄弟姐妹的家庭, 其中最年轻的, 21岁确诊, 患有严重的麦克特尔综合症. 大发娱乐在这个病人身上发现了基因突变.10 His two sisters (aged 26 and 28) showed completely healthy eye exams, 尽管其中一人携带了基因突变. 尽管有健康的临床检查, FLIO已经在这个女人身上显示了与mactel相关的变化, which may lead to an earlier treatment that might preserve her 愿景.

FLIO is a promising new technology that holds the potential to revolutionize how clinicians diagnose and treat diseases. 通过在损害显现之前发现变化, FLIO may be a beneficial tool for clinical care in the near future.

关于作者

Dr. 伯恩斯坦擅长玻璃体视网膜疾病和外科手术, 视网膜生物化学, 以及黄斑变性和视网膜变性. He directs clinical 研究 and serves as associate director of 研究 at the 莫兰眼科中心.

Dr. 绍尔是一名研究助理 伯恩斯坦实验室 谁专门研究FLIO.

脚注

1. Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. 调查眼科 & 视觉科学1995;36:718-729.

2. 施韦策D,科尔布A,哈默M,安德斯R. 自体荧光的时间相关测量. 一种检测眼底代谢变化的方法. Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft 2002;99:774-779.

3. Lakowicz小. 荧光光谱学原理. Springer; 2006.

4. Dysli C, Wolf S, Berezin MY, 萨奥尔L, Hammer M, Zinkernagel MS. 荧光终身成像检眼镜. 视网膜与眼科学进展2017;60:120-143.

5. 萨奥尔L, Andersen KM, Dysli C, Zinkernagel MS, 伯恩斯坦PS, Hammer M. Review of clinical approaches in fluorescence lifetime imaging ophthalmoscopy. 生物医学光学,2018;23:1-20.

6. Charbel Issa P, Gillies米C, Chew EY等. 2型黄斑毛细血管扩张. 视网膜与眼科学进展2013;34 (4):49-77.

7. Chew EY, Clemons TE, Peto T,等. Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial. 中华眼科杂志2015;59:659-666.

8. 萨奥尔L, Gensure RH, Hammer M, 伯恩斯坦PS. Fluorescence Lifetime Imaging Ophthalmoscopy: A Novel Way to Assess Macular Telangiectasia Type 2. 中华眼科杂志2018;2:587-598.

9. 萨奥尔L, Vitale AS, Andersen KM, Hart B, 伯恩斯坦PS. Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) Patterns in Clinically Unaffected Children of Macular Telangiectasia Type 2 (MacTel) 病人. 视网膜2019.

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