Quantitative Analysis of Fluorescence Lifetime Measurements of the Macula Using the Fluorescence Lifetime Imaging Ophthalmoscope in Healthy Subjects

Dysli, Chantal; Quellec, Gwénolé; Abegg, Mathias; Menke, Marcel N.; Wolf-Schnurrbusch, Ute; Kowal, Jens; Blatz, Johannes; Schiazza, Olivier La; Leichtle, Alexander Benedikt; Wolf, Sebastián; Zinkernagel, Martin S.

doi:10.1167/iovs.13-13627

Cited by 105 publications

(196 citation statements)

References 14 publications

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“…An industrially designed prototype device, based on the Heidelberg Engineering Spectralis scanner, was first used by Dysli et al (Dysli et al, 2014b). More recent clinical research with this device is described in later sections of this review.…”

Section: Historical Backgroundmentioning

confidence: 99%

“…They allow continuous overlay of the fluorescence intensity image and the color coded image of single lifetime components (Tm, T1, T2, a1, a2, photon count, chi-square value, (ETDRS) grid with circle diameters of 1 mm for the central area (C), 3 mm for the inner ring (IR) and 6 mm for the outer ring (OR) can be used to analyze areas of interest (Dysli et al, 2014b). The grid is adjustable in position and if needed also in size.…”

Section: Image Analysis Softwarementioning

confidence: 99%

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Fluorescence lifetime imaging ophthalmoscopy

Dysli

Wolf

Zinkernagel

2017

Acta Ophthalmologica

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a b s t r a c tImaging techniques based on retinal autofluorescence have found broad applications in ophthalmology because they are extremely sensitive and noninvasive. Conventional fundus autofluorescence imaging measures fluorescence intensity of endogenous retinal fluorophores. It mainly derives its signal from lipofuscin at the level of the retinal pigment epithelium. Fundus autofluorescence, however, can not only be characterized by the spatial distribution of the fluorescence intensity or emission spectrum, but also by a characteristic fluorescence lifetime function. The fluorescence lifetime is the average amount of time a fluorophore remains in the excited state following excitation. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is an emerging imaging modality for in vivo measurement of lifetimes of endogenous retinal fluorophores. Recent reports in this field have contributed to our understanding of the pathophysiology of various macular and retinal diseases.Within this review, the basic concept of fluorescence lifetime imaging is provided. It includes technical background information and correlation with in vitro measurements of individual retinal metabolites. In a second part, clinical applications of fluorescence lifetime imaging and fluorescence lifetime features of selected retinal diseases such as Stargardt disease, age-related macular degeneration, choroideremia, central serous chorioretinopathy, macular holes, diabetic retinopathy, and retinal artery occlusion are discussed. Potential areas of use for fluorescence lifetime imaging ophthalmoscopy will be outlined at the end of this review.

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Section: Historical Backgroundmentioning

confidence: 99%

Section: Image Analysis Softwarementioning

confidence: 99%

Fluorescence lifetime imaging ophthalmoscopy

Dysli

Wolf

Zinkernagel

2017

Acta Ophthalmologica

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“…19 Subjects suffering from systemic diseases that could influence ocular metabolism were not included. Because the fluorescence decay depends on age, 20,21 the only subjects who were included in the age-matched comparison between diabetic patients who have no signs of DR and healthy subjects were older than 40 years. The investigation was performed predominantly on subjects with a crystalline lens.…”

Section: Participantsmentioning

confidence: 99%

Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy

et al. 2015

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Abstract. The time-resolved autofluorescence of the eye is used for the detection of metabolic alteration in diabetic patients who have no signs of diabetic retinopathy. One eye from 37 phakic and 11 pseudophakic patients with type 2 diabetes, and one eye from 25 phakic and 23 pseudophakic healthy subjects were included in the study. After a three-exponential fit of the decay of autofluorescence, histograms of lifetimes τ i , amplitudes α i , and relative contributions Q i were statistically compared between corresponding groups in two spectral channels (490 < ch1 < 560 nm, 560 < ch2 < 700 nm). The change in single fluorophores was estimated by applying the Holm-Bonferroni method and by calculating differences in the sum histograms of lifetimes. Median and mean of the histograms of τ 2 , τ 3 , and α 3 in ch1 show the greatest differences between phakic diabetic patients and age-matched controls (p < 0.000004). The lack of pixels with a τ 2 of ∼360 ps, the increased number of pixels with τ 2 > 450 ps, and the shift of τ 3 from ∼3000 to 3700 ps in ch1 of diabetic patients when compared with healthy subjects indicate an increased production of free flavin adenine dinucleotide, accumulation of advanced glycation end products (AGE), and, probably, a change from free to protein-bound reduced nicotinamide adenine dinucleotide at the fundus. AGE also accumulated in the crystalline lens.

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“…An alternative method to steady-state fluorometry is time-resolved fluorometry, namely fluorescence lifetime measurement (FLM), and this approach is widely used together with steady-state fluorometry in clinical settings [8][9][10]. However, there have been few reports on the application of FLM to examination of AGEs.…”

Section: Introductionmentioning

confidence: 99%

Decrease in fluorescence lifetime by glycation of collagen and its application in determining advanced glycation end-products in human dentin

Fukushima¹,

Shimizu²,

Miura³

et al. 2015

Biomed. Opt. Express

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Advanced Glycation End-products (AGEs) are produced by the Maillard reaction, which causes cross-linking of collagen and results in changes in the mechanical properties of collagen tissues. Several types of AGE fluoresce, and measurement of this fluorescence is effective for determining the presence of AGEs. Because fluorescence intensity by steady-state fluorometry is affected by sample surface condition and light source, we focused on fluorescence lifetime measurement (FLM). We found that fluorescence lifetime of collagen gel decreased with glycation progress. In vivo application of FLM for determination of AGEs was confirmed in human dentin. 309-318 (1999 248-254 (1976). 14. R. Longin, "New method of collagen extraction for radiocarbon dating," Nature 230(5291), 241-242 (1971). 15. J. Meng, N. Sakata, Y. Imanaga, S. Takebayashi, R. Nagai, and S. Horiuchi, "Carboxymethyllysine in dermal tissues of diabetic and nondiabetic patients with chronic renal failure: relevance to glycoxidation damage," Nephron 88(1), 30-35 (2001). 16. U. K. Laemmli, "Cleavage of structural proteins during the assembly of the head of bacteriophage T4," Nature 227(5259), 680-685 (1970). 17. M. Laurière, "A semidry electroblotting system efficiently transfers both high-and low-molecular-weight proteins separated by SDS-PAGE," Anal. Biochem. 212(1), 206-211 (1993). 18. G. K. Reddy and C. S. Enwemeka, "A simplified method for the analysis of hydroxyproline in biological tissues,"Clin. Biochem. 29(3), 225-229 (1996). Eur.

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Quantitative Analysis of Fluorescence Lifetime Measurements of the Macula Using the Fluorescence Lifetime Imaging Ophthalmoscope in Healthy Subjects

Cited by 105 publications

References 14 publications

Fluorescence lifetime imaging ophthalmoscopy

Fluorescence lifetime imaging ophthalmoscopy

Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy

Decrease in fluorescence lifetime by glycation of collagen and its application in determining advanced glycation end-products in human dentin

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