Lessons learned from quantitative fundus autofluorescence.
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ABSTRACT:
SUBMITTER: Sparrow JR
PROVIDER: S-EPMC7561015 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Lessons learned from quantitative fundus autofluorescence.
Sparrow Janet R JR Duncker Tobias T Schuerch Kaspar K Paavo Maarjaliis M de Carvalho Jose Ronaldo Lima JRL
Progress in retinal and eye research 20190828
Quantitative fundus autofluorescence (qAF) is an approach that is built on a confocal scanning laser platform and used to measure the intensity of the inherent autofluorescence of retina elicited by short-wavelength (488 nm) excitation. Being non-invasive, qAF does not interrupt tissue architecture, thus allowing for structural correlations. The spectral features, cellular origin and topographic distribution of the natural autofluorescence of the fundus indicate that it is emitted from retinalde ...[more]
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Project description:Fundus autofluorescence was quantified (qAF) in subjects with healthy retinae using a standardized approach. The objective was to establish normative data and identify factors that influence the accumulation of RPE lipofuscin and/or modulate the observed AF signal in fundus images.AF images were acquired from 277 healthy subjects (age range: 5-60 years) by employing a Spectralis confocal scanning laser ophthalmoscope (cSLO; 488-nm excitation; 30°) equipped with an internal fluorescent reference. For each image, mean gray level was calculated as the average of eight preset regions, and was calibrated to the reference, zero-laser light, magnification, and optical media density from normative data on lens transmission spectra. Relationships between qAF and age, sex, race/ethnicity, eye color, refraction/axial length, and smoking status were evaluated as was measurement repeatability and the qAF spatial distribution.qAF levels exhibited a significant increase with age. qAF increased with increasing eccentricity up to 10° to 15° from the fovea and was highest superotemporally. qAF values were significantly greater in females, and, compared with Hispanics, qAF was significantly higher in whites and lower in blacks and Asians. No associations with axial length and smoking were observed. For two operators, between-session repeatability was ± 9% and ± 12%. Agreement between the operators was ± 13%.Normative qAF data are a reference tool essential to the interpretation of qAF measurements in ocular disease.
| S-EPMC3759220 | biostudies-literature
Project description:Purpose:To increase our understanding of the mechanisms underlying hydroxychloroquine (HCQ) retinopathy, analyses by quantitative fundus autofluorescence (qAF) and near-infrared fundus autofluorescence (NIR-AF) were compared to results obtained by recommended screening tests. Methods:Thirty-one patients (28 females, 3 males) were evaluated with standard automated perimetry and spectral domain optical coherence tomography (SD-OCT); 28 also had multifocal electroretinography (mfERG). Measurement of short-wavelength fundus autofluorescence (SW-AF) by qAF involved the use of an internal fluorescent reference and intensity measurements in eight concentric segments at 7° to 9° eccentricity. For semiquantitative analysis of NIR-AF, intensities were acquired along a vertical axis through the fovea. Results:Four of 15 high-dose (total dose >1000 g, daily dose >5.0 mg/kg) patients and one of 16 low-dose (total dose <1000 g, daily dose 4.4 mg/kg) patients were diagnosed with HCQ-associated retinopathy based on abnormal 10-2 visual fields, SD-OCT, and SW-AF imaging. Three of the high-dose patients also had abnormal mfERG results. Of the five patients exhibiting retinopathy, two had qAF color-coded images revealing higher intensities inferior, nasal, and lateral to the fovea. The abnormal visual fields also exhibited superior-inferior differences. Mean NIR-AF gray-level intensities were increased in four high-dose patients with no evidence of retinopathy. In two patients with retinopathy, NIR-AF intensity within the parafovea was below the normal range. One high-dose patient (6.25 mg/kg) had only abnormal mfERG results. Conclusions:These findings indicate that screening for HCQ retinopathy should take into consideration superior-inferior differences in susceptibility to HCQ retinopathy.
| S-EPMC7521180 | biostudies-literature
Project description:PurposeTo use multimodal retinal images (including quantitative fundus autofluorescence [QAF]) for spectral-domain optical coherence tomography (SD-OCT)-based image registration and alignment. For each age decade of healthy adults, normative fine-grained QAF retinal maps are generated and advanced methods for QAF image analysis are applied.MethodsMultimodal retinal images were obtained from 103 healthy subjects (age 19-77 years; unremarkable retina/macula, age-appropriate clear optic media). Custom written FIJI plugins enabled: (1) determination of the fovea in SD-OCT and the edge of the optic disc in infrared (IR) images; (2) alignment and superimposition of multimodal retinal images based on foveal and optic disc position; (3) plotting of normative QAF retinal maps for each decade; and (4) comparison of individual retinas with normative retinas of different decades using newly introduced analysis patterns (QAF97, freehand tool).ResultsSD-OCT based image registration enables easy image registration, alignment, and analysis of different modalities (QAF, IR, and SD-OCT here reported). In QAF, intensities significantly increase with age with two major inclines between the third/fourth and seventh/eighth decades. With aging, the parafoveal area of maximum QAF intensity slightly shifts from temporal-superior to temporal. Compared with standard QAF analysis, refined QAF analysis patterns reveal a more detailed analysis of QAF, especially in the diseased retina.ConclusionsAge-related QAF normative retinal maps can be used to directly compare and classify individual's QAF intensities. Advanced QAF analysis tools will further help to interpret autofluorescence changes in normal aging and in the diseased retina in a multimodal imaging setting.Translational relevanceAdvanced methods for QAF analysis link basic findings with clinical observations in normal aging and in the diseased macula.
| S-EPMC7422829 | biostudies-literature
Project description:PurposeTo investigate the effect of systemic chloroquine/hydroxychloroquine (CQ/HCQ) on outer retinal health using quantitative fundus autofluorescence (QAF) imaging.MethodsFor this prospective, cross-sectional study, 44 CQ/HCQ patients and 25 age-matched controls underwent multimodal retinal imaging including QAF (488 nm) and spectral-domain optical coherence tomography (SD-OCT) in addition to the recommended CQ/HCQ screening procedures. Custom written FIJI plugins enabled detailed QAF analysis and correlation with retinal thickness and comparison to the healthy controls.ResultsOut of 44 patients, 29 (mean age 43.5 ± 12.2, range 22-59 years) exposed to CQ/HCQ (mean cumulative dose 724.2 ± 610.4 g, median 608.0 g, range 18.6-2171.0 g) met eligibility criteria. Four of these 29 patients had bull's-eye maculopathy (BEM). Mean QAF values were significantly higher in CQ/HCQ patients than in healthy controls. QAF increase started early after treatment onset, remained high even years after treatment cessation, and was not accompanied by pathologies in the other screening methods, including retinal thicknesses (except in BEM patients).ConclusionsQAF might be a useful tool in retinal imaging and in verifying systemic CQ/HCQ intake. The early onset and preserved high levels of QAF parallel findings of CQ deposition in the retina in animal models. Whether QAF can be used as a screening tool to detect early CQ/HCQ related maculopathy is the subject of long-term ongoing studies.Translation relevanceExperimental QAF imaging in systemic CQ/HCQ therapy monitoring might be a useful tool to indicate the drug or its metabolites and to detect metabolic retinal changes.
| S-EPMC7463177 | biostudies-literature
Project description:PurposeQuantitative fundus autofluorescence (QAF) enables comparisons of autofluorescence intensities among participants. While clinical QAF reports mostly focused on the healthy and diseased adult retina, only very limited data of QAF in the maturing eye are available. Here, we report QAF in a large cohort of healthy children.MethodsIn this prospective monocentric cross-sectional study, 70 healthy Caucasian children (5-18 years) were multimodal imaged, including QAF and spectral domain optical coherence tomography. QAF and retinal thicknesses were measured at predefined locations (along horizontal meridian; Early Treatment Diabetic Retinopathy Study [ETDRS] grid) and correlated using custom written Fiji plugins. Standard retinae for different age groups were generated.ResultsFifty-three participants were included. QAF was low in childhood but increased steadily (P < 0.001), also at the fovea (P < 0.001), with no gender differences (P = 0.61). The QAF distribution was similar to adults showing highest values superior-temporally. At individual points, retinal thickness remained stable, while using the ETDRS pattern, the retinal pigment epithelium (RPE) thickness increased significantly with aging. Standard QAF retinae of age groups also showed an increase with aging.ConclusionsQAF can be reliably performed in young children. Function-structure correlation showed a thickening of the RPE and an increasing QAF with aging, probably related to the histologic low number of RPE autofluorescent granules at a younger age but further deposition of these granules during maturation. Standard retinae help to distinguish abnormal QAF in the diseased retina of age-matched patients.Translational relevanceOur data bridge the gap between preclinical QAF and clinical data application and structural OCT correlation in children.
| S-EPMC7884289 | biostudies-literature
Project description:Purpose:To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD). Methods:The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis. Results:Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001). Conclusions:In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.
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Project description:PURPOSE:Quantitative fundus autofluorescence (qAF) and spectral-domain optical coherence tomography (SD OCT) were performed in patients with bull's-eye maculopathy (BEM) to identify phenotypic markers that can aid in the differentiation of ABCA4-associated and non-ABCA4-associated disease. DESIGN:Prospective cross-sectional study at an academic referral center. SUBJECTS:Thirty-seven BEM patients (age range, 8-60 years) were studied. All patients exhibited a localized macular lesion exhibiting a smooth contour and qualitatively normal-appearing surrounding retina without flecks. Control values consisted of previously published data from 277 healthy subjects (374 eyes; age range, 5-60 years) without a family history of retinal dystrophy. METHODS:Autofluorescence (AF) images (30°, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The grey levels (GLs) from 8 circularly arranged segments positioned at an eccentricity of approximately 7° to 9° in each image were calibrated to the reference (0 GL), magnification, and normative optical media density to yield qAF. In addition, horizontal SD OCT images through the fovea were obtained. All patients were screened for ABCA4 mutations using the ABCR600 microarray, next-generation sequencing, or both. MAIN OUTCOME MEASURES:Quantitative AF, correlations between AF and SD OCT, and genotyping for ABCA4 variants. RESULTS:ABCA4 mutations were identified in 22 patients, who tended to be younger (mean age, 21.9±8.3 years) than patients without ABCA4 mutations (mean age, 42.1±14.9 years). Whereas phenotypic differences were not obvious on the basis of qualitative fundus AF and SD OCT imaging, with qAF, the 2 groups of patients were clearly distinguishable. In the ABCA4-positive group, 37 of 41 eyes (19 of 22 patients) had qAF8 of more than the 95% confidence interval for age. Conversely, in the ABCA4-negative group, 22 of 26 eyes (13 of 15 patients) had qAF8 within the normal range. CONCLUSIONS:The qAF method can differentiate between ABCA4-associated and non-ABCA4-associated BEM and may guide clinical diagnosis and genetic testing.
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Project description:We set out to characterize the pattern of fundus autofluorescence (AF) loss in choroideremia (CHM) patients of varying ages and disease severity in order to determine the average rate of progression of this potential disease biomarker.Fifty consecutive CHM patients (100 eyes) attending outpatient clinics at Oxford Eye Hospital underwent analysis with the Heidelberg OCT Spectralis with autofluorescence capabilities. The area of residual AF was traced using Heidelberg Eye Explorer. Bland-Altman analysis was used to calculate the coefficient of repeatability (CR). The degree of AF loss was correlated to different ages and the pattern of residual AF constructed into color-coded maps in order to gain insight into the mechanism of disease progression.The CR for measurement of AF area is <1%, indicating that a small change is likely to be significant. Correlation of patient age and area of residual AF produced a clinically relevant index of expected anatomic disease. Progression is 7.7% of the residual area each year (95% confidence intervals 7.0%-8.2%) and follows a logarithmic pattern with age (r = 0.95, P < 0.001). From this we derived the mean half-life of AF as 9 years. Qualitatively, the pattern of remaining AF centered on a point temporal to the fovea.The area of residual AF in CHM can be measured reproducibly and shows a distinct pattern of loss. The measured residual area is inversely correlated to age. The ratio of the two variables may provide useful information regarding the rate of progression for any one individual at a given point in time.
| S-EPMC5860725 | biostudies-literature
Project description:PurposeThe present study aimed to evaluate the characteristics of fundus autofluorescence in Japanese patients with retinal angiomatous proliferation (RAP).MethodsWe retrospectively reviewed 100 eyes from 76 patients (male, n = 45; female, n = 31; age range, 50-94 years; mean ± standard deviation, 81.4 ± 6.4 years) with treatment-naïve RAP, which was diagnosed based on the identification of retinal-retinal anastomosis on early-phase fluorescein angiography or indocyanine green angiography (ICGA) and the identification of a hot spot on late-phase ICGA. RAP was classified into the following three stages: stage 1, proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization); stage 2, growth of the retinal vessels into the subretinal space (subretinal neovascularization); and stage 3, clinically or angiographically observed choroidal neovascularization. In all cases, short-wavelength and near-infrared autofluorescence (SW-AF, NIR-AF) was evaluated using a confocal scanning laser ophthalmoscope.ResultsThe conditions of the 100 eyes were as follows: stage 1 RAP, n = 6 (6%); stage 2 RAP without retinal pigment epithelial detachment (PED), n = 40 (40%); stage 2 RAP with PED, n = 44 (44%); and stage 3 RAP, 10 (10%). On NIR-AF imaging, the number of abnormalities that were observed to correspond to the RAP lesions on ICGA (87 eyes, 87%) was significantly greater in comparison to SW-AF imaging (27 eyes, 27%). The mean follow-up period in all 76 patients was 39.2 months. In the 76 patients with unilateral disease, 21 (21%) eyes developed RAP in the fellow eye during the follow-up period. Among 18 eyes that were examined by both SW-AF and NIR-AF imaging before the onset of RAP lesions, NIR-AF imaging showed hypoautofluorescence in 15 (83%) eyes before the onset of RAP lesions.ConclusionsSW-AF and NIR-AF abnormalities may be related to the dysfunction of the photoreceptor/retinal pigment epithelium complex. Hypoautofluorescence on NIR-AF imaging may accurately indicate the presence or onset of RAP lesions.
| S-EPMC7725377 | biostudies-literature
Project description:To quantify retinal fluorescence lifetimes in patients with central serous chorioretinopathy (CSC) and to identify disease specific lifetime characteristics over the course of disease.Forty-seven participants were included in this study. Patients with central serous chorioretinopathy were imaged with fundus photography, fundus autofluorescence, optical coherence tomography, and fluorescence lifetime imaging ophthalmoscopy (FLIO) and compared with age-matched controls. Retinal autofluorescence was excited using a 473-nm blue laser light and emitted fluorescence light was detected in 2 distinct wavelengths channels (498-560 nm and 560-720 nm). Clinical features, mean retinal autofluorescence lifetimes, autofluorescence intensity, and corresponding optical coherence tomography (OCT) images were further analyzed.Thirty-five central serous chorioretinopathy patients with a mean visual acuity of 78 ETDRS letters (range, 50-90; mean Snellen equivalent: 20/32) and 12 age-matched controls were included. In the acute stage of central serous chorioretinopathy, retinal fluorescence lifetimes were shortened by 15% and 17% in the respective wavelength channels. Multiple linear regression analysis showed that fluorescence lifetimes were significantly influenced by the disease duration (P < 0.001) and accumulation of photoreceptor outer segments (P = 0.03) but independent of the presence or absence of subretinal fluid. Prolonged central macular autofluorescence lifetimes, particularly in eyes with retinal pigment epithelial atrophy, were associated with poor visual acuity.This study establishes that autofluorescence lifetime changes occurring in central serous chorioretinopathy exhibit explicit patterns which can be used to estimate perturbations of the outer retinal layers with a high degree of statistical significance.
| S-EPMC5690302 | biostudies-literature