Quantitative Fundus Autofluorescence Imaging Research Articles

Personalized Lens Correction Improves Quantitative Fundus Autofluorescence Analysis.

Quantitative fundus autofluorescence (QAF) currently deploys an age-based score to correct for lens opacification. However, in elderly people, lens opacification varies strongly between individuals of similar age, and innate lens autofluorescence is not included in the current correction formula. Our goal was to develop and compare an individualized formula. One hundred thirty participants were examined cross-sectionally, and a subset of 30 participants received additional multimodal imaging 2-week post-cataract-surgery. Imaging included the Scheimpflug principle, anterior chamber optical coherence tomography (AC-OCT), lens quantitative autofluorescence (LQAF), and retinal QAF imaging. Among the subset, least absolute shrinkage and selection operator regression and backward selection was implemented to determine which lens score best predicts the QAF value after lens extraction. Subsequently, a spline mixed model was applied to the whole cohort to quantify the influence of LQAF and Scheimpflug on QAF. Age and LQAF measurements were found to be the most relevant variables, whereas AC-OCT measurements and Scheimpflug were eliminated by backward selection. Both an increase in Scheimpflug and LQAF values were associated with a decrease in QAF. The prediction error of the spline model (mean absolute error [MAE] ± standard deviation) of 32.2 ± 23.4 (QAFa.u.) was markedly lower compared to the current age-based formula MAE of 96.1 ± 93.5. Both smooth terms, LQAF (P < 0.01) and Scheimpflug (P < 0.001), were significant for the spline mixed model. LQAF imaging proved to be the most predictive for the impact of the natural lens on QAF imaging. The application of lens scores in the clinic could improve the accuracy of QAF imaging interpretation and might allow including aged patients in future QAF studies.

Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy.

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.

Fundus autofluorescence imaging.

Fundus autofluorescence (FAF) imaging is an in vivo imaging method that allows for topographic mapping of naturally or pathologically occurring intrinsic fluorophores of the ocular fundus. The dominant sources are fluorophores accumulating as lipofuscin in lysosomal storage bodies in postmitotic retinal pigment epithelium cells as well as other fluorophores that may occur with disease in the outer retina and subretinal space. Photopigments of the photoreceptor outer segments as well as macular pigment and melanin at the fovea and parafovea may act as filters of the excitation light. FAF imaging has been shown to be useful with regard to understanding of pathophysiological mechanisms, diagnostics, phenotype-genotype correlation, identification of prognostic markers for disease progression, and novel outcome parameters to assess efficacy of interventional strategies in chorio-retinal diseases. More recently, the spectrum of FAF imaging has been expanded with increasing use of green in addition to blue FAF, introduction of spectrally-resolved FAF, near-infrared FAF, quantitative FAF imaging and fluorescence life time imaging (FLIO). This article gives an overview of basic principles, FAF findings in various retinal diseases and an update on recent developments.

Quantitative Fundus Autofluorescence and Genetic Associations in Macular, Cone, and Cone–Rod Dystrophies

To investigate quantitatively lipofuscin-associated fundus autofluorescence in patients with macular and cone/cone-rod dystrophies (MD/CCRDs). Prospective, single-center, case-control study. Two hundred thirty patients with MD/CCRDs who had undergone genetic testing and 110 control participants without any eye disease. Participants were examined using quantitative fundus autofluorescence (qAF) imaging with a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference (modified Spectralis HRA-OCT; Heidelberg Engineering, Heidelberg, Germany). Mean qAF values were obtained by averaging measurements from an 8-segment ring centered on the fovea (qAF8) and compared with controls. The qAF8 levels. Elevated qAF8 values were a frequent finding (n= 105 [45%]) and associated with ABCA4 (n= 73 [70%]), PRPH2 (n= 9 [9%]), CERKL (n= 3 [3%]), PROM1 (n= 2 [2%]), CRX (n= 1 [1%]), and CDHR1 (n= 1 [1%]) mutations. Reduced qAF8 values were rare (n= 15 [7%]) and found predominantly among patients with MERTK (n= 3 [20%]) and RDH5 (n= 2 [13%]) mutations. Patients with normal qAF8 values (n= 110 [48%]) showed high genotypic heterogeneity. For various genes including ABCA4, PRPH2, CDHR1, and PROM1, higher qAF8 measures were associated with specific phenotypes and genotypes. For instance, qAF8 values were normal in PRPH2-related central areolar chorioretinal dystrophy but increased in PRPH2-related Stargardt-like retinopathy. Accordingly, high qAF8 levels were associated with specific genetic causes and mutation detection rates in characteristic but genetically heterogenous clinical phenotypes, such as a Stargardt-like flecked fundus, bull's eye maculopathy, or pattern dystrophy. In genetically unsolved cases (16 with elevated, 35 with normal, 7 with reduced qAF values), qAF8 was used to support or reject ambiguous results of genetic testing, to suggest underlying pathogenic pathways, and to predict disease in otherwise healthy participants. Quantitative fundus autofluorescence imaging revealed characteristic qAF levels in association with certain gene mutations and in participants without detected mutations. These findings indicate that qAF may facilitate differential diagnostics of MD/CCRDs and may offer novel pathogenetic insights that may be of particular value for the assessment of future treatment approaches.

Repeatability and reliability of quantitative fundus autofluorescence imaging in patients with early and intermediate age-related macular degeneration.

Quantification of fundus autofluorescence has only recently become available. We report our findings on the evaluation of the repeatability and reliability of quantitative fundus autofluorescence (qAF) measurements in patients with early and intermediate age-related macular degeneration (AMD), using the first approved and commercially available instrument. A total of 43 eyes of 22 patients (aged between 52 and 84years) diagnosed with early and intermediate AMD were included. All eyes were imaged at day 1, 3months and 6months using a modified scanning laser ophthalmoscope, equipped with an internal fluorescent reference. Mean qAF values were calculated for the fovea and for each concentric ring of the Delori pattern. Repeatability and reliability were calculated using Bland-Altman analysis and intraclass correlation (ICC). The mean patient age was 73.5±7.9years. Sixteen patients (73%) were female. qAF repeatability of the eight segments in the middle ring of the Delori pattern (qAFM 8 ) for between sessions was ±8.2%. Agreement at 3- and 6-month follow-up in eyes without retinal changes was ±8.3% and ±9.8%, respectively. Reliability of qAFM 8 was high for all images acquired [ICC=0.98 (CI: 0.96-0.99), 0.97 (0.93-0.99) and 0.98 (0.92-0.99)]. Agreement at 3- and 6-month follow-up in eyes with retinal changes was ±18.1% and ±20.2%, respectively. Intraclass correlation (ICC) was slightly lower in eyes with retinal changes at 0.93 (0.84-0.97) and 0.96 (0.91-0.98), respectively. Quantitative autofluorescence shows excellent repeatability and reliability as well as follow-up agreement in patients with early and intermediate AMD without retinal changes. This is relevant when conducting longitudinal studies using qAF.

Visible-light optical coherence tomography-based multimodal system for quantitative fundus autofluorescence imaging.

Quantitative fundus autofluorescence imaging with simultaneous visible-light optical coherence tomography-based multimodal technology has potential significant impact on the diagnosis and monitoring the progression of retinal diseases.

Fundus Autofluorescence Imaging

Fundus autofluorescence (FAF) imaging allows for non-invasive mapping of changes at the level of the retinal pigment epithelium/photoreceptor complex and of alterations of macular pigment distribution. This imaging method is based on the visualisation of intrinsic fluorophores and may be easily and rapidly used in routine patient care. Main applications include degenerative disorders of the outer retina such as age-related macular degeneration, hereditary and acquired retinal diseases. FAF imaging is particularly helpful for differential diagnosis, detection and extent of involved retinal areas, structural-functional correlations and monitoring of changes over time. Recent developments include - in addition to the original application of short wavelength light for excitation ("blue" FAF imaging) - the use of other wavelength ranges ("green" or "near-infrared" FAF imaging), widefield imaging for visualisation of peripheral retinal areas and quantitative FAF imaging.