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Purpose: To observe fundus autofluorescence (FAF) lifetimes and peak emission wavelength (PEW) of drusen with respect to the pathology of the overlying RPE in the follow-up of AMD-patients., Methods: Forty eyes of 38 patients (age: 75.1 ± 7.1 years) with intermediate AMD were included. FAF lifetimes and PEW were recorded by fluorescence lifetime imaging ophthalmoscopy (FLIO). Twenty-six eyes had a follow-up investigation between months 12 and 36, and 10 at months 37-72. AMD progression was retrieved from color fundus photography (CFP) and OCT. Drusen were classified with respect to changes in the overlying RPE into groups no, questionable or faint, and apparent hyperpigmentation based on CFP., Results: Among the 210 hyperautofluorescent drusen found at baseline, those with hyperpigmentation had longer lifetimes and shorter PEW than those without. Drusen without hyperpigmentation had shorter lifetimes and PEW than neighboring RPE (all p < 0.001) at baseline, but drusen lifetimes increased, and PEW shortened further over follow-up. Eyes, showing AMD progression, had significantly longer FAF lifetimes at baseline than non-progressing eyes: 282 ± 102 ps versus 245 ± 98 ps, p < 0.001 and 365 ± 44 ps vs. 336 ± 48 ps, p = 0.025 for short and long wavelength FLIO channel, respectively., Conclusions: Depending on hyperpigmentation properties, drusen show lifetimes and PEW different from that of adjacent RPE which change over the natural history of AMD. This difference and change, however, might reflect progressive dysmorphia of the RPE rather than representing fluorescence of drusen material itself. Nevertheless, the observed FAF changes could make FLIO a useful tool for the early detection of AMD progression risk., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To measure fundus autofluorescence (FAF) lifetimes and peak emission wavelengths (PEW) of subretinal drusenoid deposits (SDD) in age-related macular degeneration (AMD) and their development over time., Methods: Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in 30 eyes with optical coherence tomography (OCT)-confirmed early or intermediate AMD and SDD. Contrasts of mean lifetimes in short- (SSC) and long-wavelength channels (LSC), PEW, and relative fluorescence intensity were determined as differences of the respective measures at individual SDD and their environment. Measurements were made at baseline and at follow-up intervals 1 (13-36 months) and 2 (37-72 months), respectively., Results: Of 423 SDD found at baseline, 259, 47, and 117 were hypoautofluorescent, isoautofluorescent, and hyperautofluorescent, respectively. FAF lifetimes of SDD were significantly longer than those of their environment by 14.5 ps (SSC, 95% confidence interval [CI], 13.3-15.7 ps) and 3.9 ps (LSC, 3.1-4.7 ps). PEW was shorter by 1.53 nm (1.07-1.98 nm, all contrasts P < 0.001) with higher contrasts for hyperfluorescent SDD. Over follow-up, SDD tended to hyperautofluorescence (relative intensities increased by 3.4% [95% CI, 2.9%-4.1%; P < 0.001] in follow-up 2). Hyperautofluorescence was associated with disruption of the ellipsoid zone on OCT. Disease progression to late-stage AMD was associated with higher lifetime contrast in SSC (15.9ps [14.2-17.6 ps] vs. 11.7 ps [9.9-13.5 ps], P < 0.001) at baseline., Conclusions: SDD show longer FAF lifetimes and shorter PEW than their environments. A high lifetime contrast of SDD in SSC might predict disease progression to late-stage AMD.

Purpose: The purpose of this study was to investigate histologic autofluorescence lifetimes and spectra of retinal pigment epithelium (RPE) on the transition from normal aging to RPE activation and migration in age-related macular degeneration (AMD)., Methods: Autofluorescence lifetimes and spectra of 9 donor eyes were analyzed in cryosections by means of 2-photon excited fluorescence at 960 nm. Spectra were detected at 483 to 665 nm. Lifetimes were measured using time-correlated single photon counting in 2 spectral channels: 500 to 550 nm (short-wavelength spectral channel [SSC]) and 550 to 700 nm (long-wavelength spectral channel [LSC]). Fluorescence decays over time were approximated by a series of three exponential functions. The amplitude-weighted mean fluorescence lifetime was determined. Markers for retinoid activity (RPE65) and immune function (CD68) were immunolocalized in selected neighboring sections., Results: We identified 9 RPE morphology phenotypes resulting in 399 regions of interest (ROIs) for spectral and 497 ROIs for lifetime measurements. RPE dysmorphia results in a shorter wavelength peak of spectral emission: normal aging versus RPE migrated into the retina (intraELM) = 601.7 (9.5) nm versus 581.6 (7.3) nm, P < 0.001, whereas autofluorescence lifetimes increase: normal aging versus intraELM: SSC 180 (44) picosecond (ps) versus 320 (86) ps, P < 0.001; and LSC 250 (55) ps versus 441 (76) ps, P < 0.001. Ectopic RPE within the neurosensory retina is strongly CD68 positive and RPE65 negative., Conclusions: In the process of RPE degeneration, comprising different steps of dysmorphia and migration, lengthening of autofluorescence lifetimes and a hypsochromic shift of emission spectra can be observed. These autofluorescence changes might provide early biomarkers for AMD progression and contribute to our understanding of RPE-driven pathology.

Purpose: To determine the fundus autofluorescence (FAF) lifetimes and spectral characteristics of individual drusen and hyperpigmentation independent of those with retinal pigment epithelium (RPE) in geographic atrophy (GA) areas in late-stage age-related macular degeneration (AMD)., Methods: Three consecutive patients with complete RPE and outer retinal atrophy (cRORA) exhibiting drusen that were calcified or associated with hyperpigmentation were investigated with multimodal non-invasive ophthalmic imaging including colour fundus photography (CFP), optical coherence tomography (OCT), near-infrared reflectance (NIR), blue FAF and fluorescence lifetime imaging ophthalmoscopy (FLIO). Fluorescence lifetimes were measured in two spectral channels (short-wavelength spectral channel (SSC): 500-560 nm and long-wavelength spectral channel (LSC): 560-720 nm)., Results: Drusen lacking RPE coverage, as confirmed by CFP and OCT, had longer FAF lifetimes than surrounding cRORA by 127 ± 66 ps (SSC) and 113 ± 48 ps (LSC, both p = 0.008 in Wilcoxon test, N = 9) and by 209 ± 100 ps (SSC) and 121 ± 56 ps (LSC, p < 0.001, N = 14) in two patients. Hyperpigmentation in CFP in a third patient shows strong FAF with prolonged lifetimes. In the SSC, persistent FAF was found inside cRORA. A crescent-shaped hyperfluorescence in an area of continuous RPE but lacking outer retina was seen in one eye with a history of anti-VEGF treatment., Conclusions: Short-wavelength fluorescence in cRORA points to fluorophores beyond RPE organelles. Fluorescence properties of drusen within cRORA differ from in vivo drusen covered by RPE. These limited findings from three patients give new insight into the sources of FAF that can be further elucidated in larger cohorts., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The purpose of this study was to observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO)., Methods: Multimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization (mean age = 74.2 ± 7.0 years). Twenty-three eyes were followed for 28.3 ± 18.3 months. Seven eyes had a second follow-up after 46.6 ± 9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, hyper-reflective foci (HRF) on OCT, attributed to single or clustered intraretinal RPE, were identified. Fluorescence lifetimes in two spectral channels (short-wavelength spectral channel [SSC] = 500-560 nm, long-wavelength spectral channel [LSC] = 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO., Results: As hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256 ± 49 ps (SSC) and 336 ± 35 ps (LSC) and an ESIR of 0.552 ± 0.079. For hyperpigmentation, these values were 317 ± 68 ps (p < 0.001), 377 ± 56 ps (P < 0.001), and 0.609 ± 0.081 (P = 0.001), respectively, and for HRF 337 ± 79 ps (P < 0.001), 414 ± 50 ps (P < 0.001), and 0.654 ± 0.075 (P < 0.001)., Conclusions: In the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.

Purpose: To investigate the autofluorescence lifetimes as well as spectral characteristics of soft drusen and retinal hyperpigmentation in age-related macular degeneration (AMD)., Methods: Forty-three eyes with nonexudative AMD were included in this study. Fluorescence lifetime imaging ophthalmoscopy (FLIO), which detects autofluorescence decay over time in the short (SSC) and long (LSC) wavelength channel, was performed. The mean autofluorescence lifetime (τ m ) and the spectral ratio (sr) of autofluorescence emission in the SSC and LSC were recorded and analyzed. In total, 2760 soft drusen and 265 hyperpigmented areas were identified from color fundus photographs and spectral domain optical coherence tomography (SD-OCT) images and superimposed onto their respective AF images. τ m and sr of these lesions were compared with fundus areas without drusen. For clearly hyperfluorescent drusen, the local differences compared to fundus areas without drusen were determined for lifetimes and sr., Results: Hyperpigmentation showed significantly longer τ m (SSC: 341 ± 81 vs. 289 ± 70 ps, P < 0.001; LSC: 406 ± 42 vs. 343 ± 42 ps, P < 0.001) and higher sr (0.621 ± 0.077 vs. 0.539 ± 0.083, P < 0.001) compared to fundus areas without hyperpigmentation or drusen. No significant difference in τ m was found between soft drusen and fundus areas without drusen. However, the sr was significantly higher in soft drusen (0.555 ± 0.077 vs. 0.539 ± 0.081, P < 0.0005). Hyperfluorescent drusen showed longer τ m than surrounding fundus areas without drusen (SSC: 18 ± 42 ps, P = 0.074; LSC: 16 ± 29 ps, P = 0.020)., Conclusions: FLIO can quantitatively characterize the autofluorescence of the fundus, drusen, and hyperpigmentation in AMD., Translational Relevance: The experimental FLIO technique was applied in a clinical investigation. As FLIO yields information on molecular changes in AMD, it might support future diagnostics., Competing Interests: Disclosure: M. Hammer, P; R. Schultz, None; S. Hasan, None; L. Sauer, None; M. Klemm, None; L. Kreilkamp, None; L. Zweifel, None; R. Augsten, None; D. Meller, None, (Copyright 2020 The Authors.)

This article discusses the repeatability and reliability of a new measure called choriocapillaris flow deficit (FD) in optical coherence tomography angiography (OCTA). The study found that the measurement of FD using spectral-domain OCTA (SD-OCTA) is reliable and reproducible, with a high level of repeatability. However, the absolute values of FD differ between SD-OCTA and swept-source OCTA (SS-OCTA), possibly due to differences in resolution and segmentation. Overall, SD-OCTA is considered a reliable technique for measuring blood flow deficit in the choriocapillaris. [Extracted from the article]

Purpose: To investigate the spectral characteristics of fundus autofluorescence (FAF) in AMD patients and controls. Methods: Fundus autofluorescence spectral characteristics was described by the peak emission wavelength (PEW) of the spectra. Peak emission wavelength (PEW) was derived from the ratio of FAF recordings in two spectral channels at 500–560 nm and 560–720 nm by fluorescence lifetime imaging ophthalmoscopy. The ratio of FAF intensity in both channels was related to PEW by a calibration procedure. Peak emission wavelength (PEW) measurements were done in 44 young (mean age: 24.0 ± 3.8 years) and 18 elderly (mean age: 67.5 ± 10.2 years) healthy subjects as well as 63 patients with AMD (mean age: 74.0 ± 7.3 years) in each pixel of a 30° imaging field. The values were averaged over the central area, the inner and the outer ring of the ETDRS grid. Results: There was no significant difference between PEW in young and elderly controls. However, PEW was significantly shorter in AMD patients (ETDRS grid centre: 571 ± 26 nm versus 599 ± 17 nm for elderly controls, inner ring: 596 ± 17 nm versus 611 ± 11 nm, outer ring: 602 ± 16 nm versus 614 ± 11 nm). After a mean follow‐up time of 50.8 ± 10.8 months, the PEW in the patients decreased significantly by 9 ± 19 nm in the inner ring of the grid. Patients, showing progression to atrophic AMD in the follow up, had significantly (p ≤ 0.018) shorter PEW at baseline than non‐progressing patients. Conclusions: Peak emission wavelength (PEW) is related to AMD pathology and might be a diagnostic marker in AMD. Possibly, a short PEW can predict progression to retinal and/or pigment epithelium atrophy. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is known to be related to a perifoveal lengthening of fundus autofluorescence (FAF) lifetimes (Sauer et al., [2]). Over the follow-up, eight patients developed choroidal neovascularization (CNV), confirmed by fluorescein angiography, seven patients progressed to cRORA, and 32 patients remained at intermediate AMD. [Extracted from the article]

Nineteen of the drusen patients (79%) and 17 of the SDD patients (89%) showed a para-foveal ring or arc of lengthened FAF lifetimes, occupying ETDRS-outer and occasionally also the inner ring (ETDRS-inner), a typical pattern for AMD (Sauer et al. 2018), in at least one spectral channel (SSC: 13 drusen patients (54%) and 15 SDD patients (79%); LSC: 18 drusen patients (75%) and 16 SDD patients (84%)). Fluorescence lifetime and peak emission wavelength differ between AMD patients with soft drusen and sub-retinal drusenoid deposits We excluded patients with atrophy or neovascularization seen in OCT, resulting in 24 patients with drusen and 19 patients having predominantly SDD (all but two had drusen as well). [Extracted from the article]