Impact of the Aging Lens and Posterior Capsular Opacification on Quantitative Autofluorescence Imaging in Age-Related Macular Degeneration

Berlin, Andreas; Clark, Mark E.; Swain, Thomas A.; Fischer, Nathan A.; McGwin, Gerald; Sloan, Kenneth R.; Owsley, Cynthia; Curcio, Christine A.

doi:10.1167/tvst.11.10.23

Cited by 8 publications

(10 citation statements)

References 65 publications

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“…The foveal center was defined as the rise of the external limiting membrane (ELM), where cone photoreceptors are at their longest. 40 , 41 The adjusted 11-line segmentation was exported in .xml format and processed using custom software (LayerThickness_ETDRS, available at https://sites.imagej.net/CreativeComputation ) written in FIJI (Fiji Is Just ImageJ 2.0.0-rc-69/1.52p; National Institutes of Health, Bethesda, MD, USA). 42 The output was thicknesses in millimeters in the nine subfields of the Early Treatment of Diabetic Retinopathy Study (ETDRS) 43 grading grid.…”

Section: Methodsmentioning

confidence: 99%

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Owsley,

McGwin,

Swain

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer–inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium–Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores ( P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

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Section: Methodsmentioning

confidence: 99%

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Owsley,

McGwin,

Swain

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…When measuring the fluorescence from the fundus, the age-related changes in absorption properties and fluorescence of the lens need to be taken into consideration [303][304][305][306]. With age, there is a progressive build-up of lenticular chromophores absorbing initially ultraviolet, then violet, blue light, and eventually even longer-wavelength light [149].…”

Section: Imaging Of Fluorescence In the Retinamentioning

confidence: 99%

“…With age, there is a progressive build-up of lenticular chromophores absorbing initially ultraviolet, then violet, blue light, and eventually even longer-wavelength light [149]. Some of these chromophores have fluorescence properties, which can interfere with measurements of the fluorescence from the fundus by absorbing some excitation/emission light and by emitting their own fluorescence, thereby shifting the acquired emission spectrum and altering the fluorescence decay kinetics [303][304][305][306]. Moreover, with age there is an increased risk of aggregation of lens crystallins, causing light scatter that eventually becomes visible as opacities known as cataracts, all of which affect both the intensity and spectrum of detected fluorescence [303].…”

Section: Imaging Of Fluorescence In the Retinamentioning

confidence: 99%

“…While in their initial instrument, Delori et al measured the actual spectral transmission of the anterior segment and accounted for it to extract the fundus fluorescence [278], the later studies, where the effects of the anterior segment were considered, used the normative data of van de Kraats and van Norren to account for age-related decrease in spectral transmission of the lens, and therefore did not account for the great variability in the lens chromophores/fluorophores between individuals [149,307]. A recent clinical study clearly demonstrated that lens opacities can affect the measurements of quantitative fundus autofluorescence [305].…”

Section: Imaging Of Fluorescence In the Retinamentioning

confidence: 99%

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Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Różanowska¹

2023

Preprint

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Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

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“… 4 , 5 For instance, QAF has proven instrumental in studies related to age-related macular degeneration (AMD), where diminished autofluorescence is frequently observed. 6 , 7 …”

mentioning

confidence: 99%

Personalized Lens Correction Improves Quantitative Fundus Autofluorescence Analysis

von der Emde,

Rennen,

Vaisband

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose 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. Methods 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. Results 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 (QAF a.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. Conclusions 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.

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Impact of the Aging Lens and Posterior Capsular Opacification on Quantitative Autofluorescence Imaging in Age-Related Macular Degeneration

Cited by 8 publications

References 65 publications

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Personalized Lens Correction Improves Quantitative Fundus Autofluorescence Analysis

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