Clinical applications of fundus autofluorescence in retinal disease

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Abstract

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

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Most cited references 172

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In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics.

C. Kathleen Dorey, John J Weiter, François C Delori … (1995)

To characterize the intrinsic fluorescence (autofluorescence) of the human ocular fundus with regard to its excitation and emission spectra, age relationship, retinal location, and topography, and to identify the dominant fluorophore among the fundus layers. Using a novel fundus spectrophotometer, fluorescence measurements were made at 7 degrees temporal to the fovea and at the fovea in 30 normal subjects and in 3 selected patients. Topographic measurements were made in 3 subjects. Ex vivo measurements of fluorescence of human retinal pigment epithelium (RPE) were obtained and compared to in vivo data. Fundus fluorescence reveals a broad band of emission between 500 and 750 nm, a maximum of approximately 630 nm, and optimal excitation of approximately 510 nm. Exhibiting a significant increase with age, this fluorescence is highest at 7 degrees to 15 degrees from the fovea, shows a well-defined foveal minimum, and decreases toward the periphery. In vivo fluorescence spectra are consistent with those obtained ex vivo on human RPE. Measurements with short wavelength excitation are strongly influenced by ocular media absorption and reveal an additional minor fluorophore in the fovea. Spectral characteristics, correlation with age, topographic distribution, and retinal location between the choriocapillaris and the photoreceptors suggest that the dominant fundus fluorophore is RPE lipofuscin. The minor fluorophore is probably in the neurosensory retina but has not been identified.

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Prevalence of age-related macular degeneration in the US population.

Ronald Klein, Chiu-Fang Chou, Barbara E K Klein … (2011)

To examine the prevalence of age-related macular degeneration (AMD) in non-Hispanic white, non-Hispanic black, Mexican American, and other racial/ethnic groups. A US nationally representative, population-based, cross-sectional study involving a total of 5553 persons aged 40 years and older from the 2005-2008 National Health and Nutrition Examination Survey. The main outcome measure was AMD determined by the grading of 45° digital images from both eyes using a standardized protocol. In the civilian, noninstitutionalized, US population aged 40 years and older, the estimated prevalence of any AMD was 6.5% (95% confidence interval, 5.5-7.6) and the estimated prevalence of late AMD was 0.8% (95% confidence interval, 0.5-1.3). Non-Hispanic black persons aged 60 years and older had a statistically significantly lower prevalence of any AMD than non-Hispanic white persons aged 60 years and older (odds ratio = 0.37; 95% confidence interval, 0.21-0.67). Overall, the prevalence of any AMD in the 2005-2008 National Health and Nutrition Examination Survey was 6.5%, which is lower than the 9.4% prevalence reported in the 1988-1994 Third National Health and Nutrition Examination Survey. While this finding might be explained in part by possible methodological differences, these estimates are consistent with a decreasing incidence of AMD and suggest important public health care implications.

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Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.

Michael F Marmor, Ulrich Kellner, Timothy Lai … (2011)

The American Academy of Ophthalmology recommendations for screening of chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy were published in 2002, but improved screening tools and new knowledge about the prevalence of toxicity have appeared in the ensuing years. No treatment exists as yet for this disorder, so it is imperative that patients and their physicians be aware of the best practices for minimizing toxic damage. New data have shown that the risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g, of HCQ. The risk increases further with continued use of the drug. The prior recommendation emphasized dosing by weight. However, most patients are routinely given 400 mg of HCQ daily (or 250 mg CQ). This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage. A baseline examination is advised for patients starting these drugs to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use. Annual screening should begin after 5 years (or sooner if there are unusual risk factors). Newer objective tests, such as multifocal electroretinogram (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF), can be more sensitive than visual fields. It is now recommended that along with 10-2 automated fields, at least one of these procedures be used for routine screening where available. When fields are performed independently, even the most subtle 10-2 field changes should be taken seriously and are an indication for evaluation by objective testing. Because mfERG testing is an objective test that evaluates function, it may be used in place of visual fields. Amsler grid testing is no longer recommended. Fundus examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage. Patients should be aware of the risk of toxicity and the rationale for screening (to detect early changes and minimize visual loss, not necessarily to prevent it). The drugs should be stopped if possible when toxicity is recognized or strongly suspected, but this is a decision to be made in conjunction with patients and their medical physicians. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Madeline Yung: myung@mednet.ucla.edu

Michael A. Klufas: mklufas@gmail.com

David Sarraf: dsarraf@ucla.edu

Journal

Journal ID (nlm-ta): Int J Retina Vitreous

Journal ID (iso-abbrev): Int J Retina Vitreous

Title: International Journal of Retina and Vitreous

Publisher: BioMed Central (London )

ISSN (Electronic): 2056-9920

Publication date (Electronic): 8 April 2016

Publication date PMC-release: 8 April 2016

Publication date Collection: 2016

Volume: 2

Electronic Location Identifier: 12

Affiliations

[1 ]GRID grid.19006.3e, ISNI 0000000096326718, Stein Eye Institute, , David Geffen School of Medicine at University of California, ; Los Angeles, CA 90095 USA

[2 ]Greater Los Angeles VA Healthcare Center, Los Angeles, CA 90024 USA

Article

Publisher ID: 35

DOI: 10.1186/s40942-016-0035-x

PMC ID: 5088473

PubMed ID: 27847630

SO-VID: e7720007-80fc-4684-b78c-af802a7a2045

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 10 December 2015

Date accepted : 15 February 2016

Custom metadata

Keywords: fundus autofluorescence,retina,imaging,lipofuscin,age related macular degeneration,central serous retinopathy,macular dystrophy,retinitis pigmentosa,white dot syndrome,hydroxychloroquine

Data availability:

Keywords: fundus autofluorescence, retina, imaging, lipofuscin, age related macular degeneration, central serous retinopathy, macular dystrophy, retinitis pigmentosa, white dot syndrome, hydroxychloroquine

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Clinical applications of fundus autofluorescence in retinal disease

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Karger: Ophthalmology

Most cited references 172

In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics.

Prevalence of age-related macular degeneration in the US population.

Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.

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