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      The Influence of Cataract on Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO)

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          Abstract

          Purpose

          To investigate the influence of lens opacifications on fluorescence lifetime imaging ophthalmoscopy (FLIO).

          Methods

          Forty-seven eyes of 45 patients were included. Mean fluorescence lifetimes ( Tm) were recorded with a fluorescence lifetime imaging ophthalmoscope in a short spectral channel (SSC) and a long spectral channel (LSC). Retinal and lens autofluorescence lifetimes were measured in subjects before and after cataract surgery. Lens opacification was graded using the Lens Opacities Classification System III (LOCS III) classification.

          Results

          The retinal Tm decreased significantly after cataract surgery in both spectral channels (SSC: –53%, P < 0.0001; LSC: –26%, P = 0.0041). The lens Tm differed significantly between the crystalline and the artificial lens in both spectral channels ( P < 0.0001). The “nuclear opacity” and “nuclear color” score of the LOCS III classification correlated significantly with the mean Tm difference in both spectral channels ( P < 0.0001).

          Conclusions

          Lens opacification results in significantly longer retinal Tm. Therefore the lens status has to be considered when performing cross-sectional fluorescence lifetime analysis. Cataract-formation and cataract-surgery needs to be considered when conducting longitudinal studies. Grading of nuclear opacity following the LOCS III classification provides an approximate conversion formula for the mean change of lifetimes, which can be helpful in the interpretation of data in patients with lens opacities.

          Translational Relevance

          FLIO is significantly influenced by lens opacities. Using a lens opacity grading scheme and measuring fluorescence lifetimes before and after cataract surgery, an approximative conversion formula can be calculated, which enables the comparison of lifetimes after cataract surgery or over the course of time.

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          Most cited references23

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          The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group.

          To develop the Lens Opacities Classification System III (LOCS III) to overcome the limitations inherent in lens classification using LOCS II. These limitations include unequal intervals between standards, only one standard for color grading, use of integer grading, and wide 95% tolerance limits. The LOCS III contains an expanded set of standards that were selected from the Longitudinal Study of Cataract slide library at the Center for Clinical Cataract Research, Boston, Mass. It consists of six slit-lamp images for grading nuclear color (NC) and nuclear opalescence (NO), five retroillumination images for grading cortical cataract (C), and five retroillumination images for grading posterior subcapsular (P) cataract. Cataract severity is graded on a decimal scale, and the standards have regularly spaced intervals on a decimal scale. The 95% tolerance limits are reduced from 2.0 for each class with LOCS II to 0.7 for nuclear opalescence, 0.7 for nuclear color, 0.5 for cortical cataract, and 1.0 for posterior subcapsular cataract with the LOCS III, with excellent interobserver agreement. The LOCS III is an improved LOCS system for grading slit-lamp and retroillumination images of age-related cataract.
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            Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7.

            (1991)
            The Early Treatment Diabetic Retinopathy Study (ETDRS), a multicenter collaborative clinical trial supported by the National Eye Institute, was designed to assess whether argon laser photocoagulation or aspirin treatment can reduce the risk of visual loss or slow the progression of diabetic retinopathy in patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy. The 3711 patients enrolled in the ETDRS were assigned randomly to either aspirin (650 mg per day) or placebo. One eye of each patient was assigned randomly to early argon laser photocoagulation and the other to deferral of photocoagulation. Both eyes were to be examined at least every 4 months and photocoagulation was to be initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Examination of a large number of baseline ocular and patient characteristics indicated that there were no important differences between randomized treatment groups at baseline.
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              Towards metabolic mapping of the human retina.

              Functional alterations are first signs of a starting pathological process. A device that measures parameter for the characterization of the metabolism at the human eye-ground would be a helpful tool for early diagnostics in stages when alterations are yet reversible. Measurements of blood flow and of oxygen saturation are necessary but not sufficient. The new technique of auto-fluorescence lifetime measurement (FLIM) opens in combination with selected excitation and emission ranges the possibility for metabolic mapping. FLIM not only adds an additional discrimination parameter to distinguish different fluorophores but also resolves different quenching states of the same fluorophore. Because of its high sensitivity and high temporal resolution, its capability to resolve multi-exponential decay functions, and its easy combination with laser scanner ophthalmoscopy, multi-dimensional time-correlated single photon counting was used for fundus imaging. An optimized set up for in vivo lifetime measurements at the human eye-ground will be explained. In this, the fundus fluorescence is excited at 446 or 468 nm and the time-resolved autofluorescence is detected in two spectral ranges between 510 and 560 nm as well as between 560 and 700 nm simultaneously. Exciting the fundus at 446 nm, several fluorescence maxima of lifetime t1 were detected between 100 and 220 ps in lifetime histograms of 40 degrees fundus images. In contrast, excitation at 468 nm results in a single maximum of lifetime t1 = 190 +/- 16 ps. Several fundus layers contribute to the fluorescence intensity in the short-wave emission range 510-560 nm. In contrast, the fluorescence intensity in the long-wave emission range between 560 and 700 nm is dominated by the fluorescence of lipofuscin in the retinal pigment epithelium. Comparing the lateral distribution of parameters of a tri-exponential model function in lifetime images of the fundus with the layered anatomical fundus structure, the shortest component (t1 = 190 ps) originates from the retinal pigment epithelium and the second lifetime (t2 = 1,000 ps) from the neural retina. The lifetime t3 approximately 5.5 ns might be influenced by the long decay of the fluorescence in the crystalline lens. In vitro analysis of the spectral properties of expected fluorophores under the condition of the living eye lightens the interpretation of in vivo measurements. Taking into account the transmission of the ocular media, the excitation of NADH is unlikely at the fundus. Copyright 2007 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                29 April 2021
                April 2021
                : 10
                : 4
                : 33
                Affiliations
                [1 ]Department of Ophthalmology, Inselspital, Bern University Hospital, Bern, Switzerland
                Author notes
                Correspondence: Martin S. Zinkernagel, University Hospital Bern, CH-3010 Bern, Switzerland. e-mail: martin.zinkernagel@ 123456insel.ch
                Article
                TVST-20-3316
                10.1167/tvst.10.4.33
                8088233
                5c513a7a-9a66-4c40-94fe-254c27174670
                Copyright 2021 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 02 March 2021
                : 30 December 2020
                Page count
                Pages: 10
                Categories
                Article
                Article

                fluorescence lifetimes,fundus autofluorescence,retinal imaging,flio,cataract,locs iii,cataract surgery,pseudophakic

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