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Cited by 236Retinal Diseases and TreatmentsRetinal Imaging and AnalysisRetinal Development and Disorders

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Clinical applications of fundus autofluorescence in retinal disease

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Yung, Madeline, Klufas, Michael A., Sarraf, David·2016·International Journal of Retina and Vitreous
DOI 10.1186/s40942-016-0035-xPMC PMC5088473
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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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Figures

Fig. 1 Excitation and emission spectra of common retinal imaging modalities. Fluorescein angiography and fundus autofluorescence operate in the blue–green spectra of visible light, while indocyanine green angiography (ICG) utilizes the infrared spectra. The crystalline lens, a common source of interference, has an emission peak similar to that of lipofuscin. With kind permission from Springer Science + Business Media: Atlas of Fundus Autofluorescence Imaging, Chapter 5: Autofluorescence Imaging with the Fundus Camera, 2007, pp. 49–54, Spaide, Fig. 5.1
Fig. 1 Excitation and emission spectra of common retinal imaging modalities. Fluorescein angiography and fundus autofluorescence operate in the blue–green spectra of visible light, while indocyanine green angiography (ICG) utilizes the infrared spectra. The crystalline lens, a common source of interference, has an emission peak similar to that of lipofuscin. With kind permission from Springer Science + Business Media: Atlas of Fundus Autofluorescence Imaging, Chapter 5: Autofluorescence Imaging with the Fundus Camera, 2007, pp. 49–54, Spaide, Fig. 5.1CC BY · PubMed Central
Fig. 2 Bleaching effect of rhodopsin. Immediately after obtaining a 30 degree FAF (a), the 50 degree FAF (b) shows a discrete area of relative hyper-autofluorescence corresponding to an area of bleached photoreceptors resulting from the first image acquisition
Fig. 2 Bleaching effect of rhodopsin. Immediately after obtaining a 30 degree FAF (a), the 50 degree FAF (b) shows a discrete area of relative hyper-autofluorescence corresponding to an area of bleached photoreceptors resulting from the first image acquisitionCC BY · PubMed Central
Fig. 3 Comparison of common imaging systems available for fundus autofluorescence. Images of normal, healthy retina were obtained using the fundus camera with a Spaide filter (a), confocal cSLO (b), and Optos ultra-widefield systems (c)
Fig. 3 Comparison of common imaging systems available for fundus autofluorescence. Images of normal, healthy retina were obtained using the fundus camera with a Spaide filter (a), confocal cSLO (b), and Optos ultra-widefield systems (c)CC BY · PubMed Central
Fig. 4 a Causes of hyper-autofluorescence. b Causes of hypo-autofluorescence
Fig. 4 a Causes of hyper-autofluorescence. b Causes of hypo-autofluorescenceCC BY · PubMed Central
Fig. 5 Perilesional hyper-autofluorescence patterns in geographic atrophy in age-related macular degeneration. Geographic atrophy can be classified based on perilesional phenotypic FAF patterns. The subtype may impact prognosis, with diffuse and banded phenotypes portending greater risk for progression to advanced disease. Republished with permission of Association for Research in Vision and Ophthalmology, from “A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene”, Lars G. Fritsche; Monika Fleckenstein; Britta S. Fiebig; Steffen SchmitzValckenberg; Almut BindewaldWittich; Claudia N. Keilhauer; Agnes B. Renner; Friederike Mackensen; Andreas Maner; Daniel Pauleikhoff; Christine Adrion; Ulrich Mansmann; Hendrik P. N. Scholl; Frank G. Holz; Bernhard H. F. Weber, vol 53, 2012; permission conveyed through Copyright Clearance Center, Inc
Fig. 5 Perilesional hyper-autofluorescence patterns in geographic atrophy in age-related macular degeneration. Geographic atrophy can be classified based on perilesional phenotypic FAF patterns. The subtype may impact prognosis, with diffuse and banded phenotypes portending greater risk for progression to advanced disease. Republished with permission of Association for Research in Vision and Ophthalmology, from “A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene”, Lars G. Fritsche; Monika Fleckenstein; Britta S. Fiebig; Steffen SchmitzValckenberg; Almut BindewaldWittich; Claudia N. Keilhauer; Agnes B. Renner; Friederike Mackensen; Andreas Maner; Daniel Pauleikhoff; Christine Adrion; Ulrich Mansmann; Hendrik P. N. Scholl; Frank G. Holz; Bernhard H. F. Weber, vol 53, 2012; permission conveyed through Copyright Clearance Center, IncCC BY · PubMed Central
Fig. 6 Sequential fundus autofluorescence of an RPE tear. RPE tears (a) appear as well-demarcated central hypo-autofluorescence due to absent RPE with adjacent irregular hyper-autofluorescence corresponding to the retracted edges of RPE. Serial images obtained 3 weeks (b) and 1 year (c) later show resurfacing and remodeling of the lesion, with centripetal recovery of autofluorescence extending from the borders
Fig. 6 Sequential fundus autofluorescence of an RPE tear. RPE tears (a) appear as well-demarcated central hypo-autofluorescence due to absent RPE with adjacent irregular hyper-autofluorescence corresponding to the retracted edges of RPE. Serial images obtained 3 weeks (b) and 1 year (c) later show resurfacing and remodeling of the lesion, with centripetal recovery of autofluorescence extending from the bordersCC BY · PubMed Central
Fig. 7 Sequential fundus autofluorescence of an RPE tear treated with aflibercept. RPE tears (a) appear as a well-demarcated central hypo-autofluorescence due to absent RPE with adjacent irregular hyper-autofluorescence corresponding to the retracted edges of RPE. The patient received anti-VEGF therapy with half-dose aflibercept. Over time (b), the lesion shows evidence of slight remodeling and resurfacing, with early centripetal recovery of autofluorescence. Note the inferior extension of the tear. Photo courtesy of Nagiel A, Sadda S, Schwartz S, Sarraf D. “Resolution of a giant pigment epithelial detachment with half-dose aflibercept.” Retinal Cases and Brief Reports. Vol 9, Issue 4, 269–272. Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer Health. Please contact healthpermissions@wolterskluwer.com for further information
Fig. 7 Sequential fundus autofluorescence of an RPE tear treated with aflibercept. RPE tears (a) appear as a well-demarcated central hypo-autofluorescence due to absent RPE with adjacent irregular hyper-autofluorescence corresponding to the retracted edges of RPE. The patient received anti-VEGF therapy with half-dose aflibercept. Over time (b), the lesion shows evidence of slight remodeling and resurfacing, with early centripetal recovery of autofluorescence. Note the inferior extension of the tear. Photo courtesy of Nagiel A, Sadda S, Schwartz S, Sarraf D. “Resolution of a giant pigment epithelial detachment with half-dose aflibercept.” Retinal Cases and Brief Reports. Vol 9, Issue 4, 269–272. Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer Health. Please contact healthpermissions@wolterskluwer.com for further informationCC BY · PubMed Central
Fig. 8 Fundus autofluorescence of central serous chorioretinopathy. FAF (a) of a son with acute exacerbation of CSCR shows macular detachment due to acute CSCR, with hyper-autofluorescent material at the margin and inferior region of the detachment. SD-OCT (b) of the lesion shows a serous retinal detachment associated with a small pigment epithelial detachment. FAF of the patient’s asymptomatic father (c) incidentally revealed an atrophic hypo-autofluorescent gravitational tract from chronic inactive CSCR with hyper-autofluorescent margins
Fig. 8 Fundus autofluorescence of central serous chorioretinopathy. FAF (a) of a son with acute exacerbation of CSCR shows macular detachment due to acute CSCR, with hyper-autofluorescent material at the margin and inferior region of the detachment. SD-OCT (b) of the lesion shows a serous retinal detachment associated with a small pigment epithelial detachment. FAF of the patient’s asymptomatic father (c) incidentally revealed an atrophic hypo-autofluorescent gravitational tract from chronic inactive CSCR with hyper-autofluorescent marginsCC BY · PubMed Central
Fig. 9 Fundus autofluorescence of Stargardt disease. While fundus photography (a, b) and clinical examination may have non-specific findings, fundus autofluorescence (c, d) shows hyper-autofluorescent flecks with peripapillary sparing characteristic of the disease. The flecks surround a hypo-autofluorescent central macula corresponding to significant chorioretinal atrophy on SD-OCT (e)
Fig. 9 Fundus autofluorescence of Stargardt disease. While fundus photography (a, b) and clinical examination may have non-specific findings, fundus autofluorescence (c, d) shows hyper-autofluorescent flecks with peripapillary sparing characteristic of the disease. The flecks surround a hypo-autofluorescent central macula corresponding to significant chorioretinal atrophy on SD-OCT (e)CC BY · PubMed Central
Fig. 10 Robson-holder ring in retinitis pigmentosa. FAF (a) of retinitis pigmentosa shows an area of normal preserved retina at the posterior fundus bordered by a hyper-autofluorescent Robson-holder ring. Mottled hypo-autofluorescence outside the ring represents photoreceptor degeneration. These details are visible on FAF but not on fundus photography (b). Image courtesy of Heidelberg Engineering
Fig. 10 Robson-holder ring in retinitis pigmentosa. FAF (a) of retinitis pigmentosa shows an area of normal preserved retina at the posterior fundus bordered by a hyper-autofluorescent Robson-holder ring. Mottled hypo-autofluorescence outside the ring represents photoreceptor degeneration. These details are visible on FAF but not on fundus photography (b). Image courtesy of Heidelberg EngineeringCC BY · PubMed Central
Fig. 11 Fundus autofluorescence of choroideremia. Wide-field color fundus photography (a, b) shows a pale fundus with zones of choroidal atrophy in the mid-periphery, revealing the sclera underneath. Wide-field fundus autofluorescence (c, d) demonstrates corresponding zones of hyper-autofluorescence given the autofluorescent properties of the sclera. Note the central stellate island of preserved choriocapillaris and RPE in each eye that is characteristic of choroideremia. Photo credit: Srinivas Sadda, MD
Fig. 11 Fundus autofluorescence of choroideremia. Wide-field color fundus photography (a, b) shows a pale fundus with zones of choroidal atrophy in the mid-periphery, revealing the sclera underneath. Wide-field fundus autofluorescence (c, d) demonstrates corresponding zones of hyper-autofluorescence given the autofluorescent properties of the sclera. Note the central stellate island of preserved choriocapillaris and RPE in each eye that is characteristic of choroideremia. Photo credit: Srinivas Sadda, MDCC BY · PubMed Central
Fig. 12 Fundus autofluorescence of fundus albipunctatus. Fundus photography (a) demonstrates multifocal white flecks in the midperiphery with macular sparing. FAF (b) shows profoundly decreased background autofluorescence and a grainy resolution. Photo credit: Sam Yang, MD
Fig. 12 Fundus autofluorescence of fundus albipunctatus. Fundus photography (a) demonstrates multifocal white flecks in the midperiphery with macular sparing. FAF (b) shows profoundly decreased background autofluorescence and a grainy resolution. Photo credit: Sam Yang, MDCC BY · PubMed Central
Fig. 13 Ultra-widefield imaging of multiple evanescent white dot syndrome (MEWDS). Ultra-widefield FAF of active disease (a) with multifocal hyper-autofluorescence and resolution (b) 6 weeks later
Fig. 13 Ultra-widefield imaging of multiple evanescent white dot syndrome (MEWDS). Ultra-widefield FAF of active disease (a) with multifocal hyper-autofluorescence and resolution (b) 6 weeks laterCC BY · PubMed Central
Fig. 14 Spectrum of hydroxychloroquine toxicity on FAF. Compared to a normal fundus (a), hydroxychloroquine toxicity may manifest in a parafoveal pattern (b), mixed pattern (c), or pericentral pattern of characteristic FAF abnormalities (d). With kind permission from Elsevier: Ophthalmology, “Pericentral retinopathy and racial differences in hydroxychloroquine toxicity,” 2015, pp. 110–116, Melles and Marmor, Fig. 1
Fig. 14 Spectrum of hydroxychloroquine toxicity on FAF. Compared to a normal fundus (a), hydroxychloroquine toxicity may manifest in a parafoveal pattern (b), mixed pattern (c), or pericentral pattern of characteristic FAF abnormalities (d). With kind permission from Elsevier: Ophthalmology, “Pericentral retinopathy and racial differences in hydroxychloroquine toxicity,” 2015, pp. 110–116, Melles and Marmor, Fig. 1CC BY · PubMed Central
Fig. 15 Multi-modal imaging of didanosine-induced (DDI) toxicity. Widefield FAF (a, b) demonstrated diffuse, bilateral midperipheral areas of well-circumscribed hypo-autofluoresence secondary to DDI toxicity. SD-OCT through the fovea (c, d) reveals macular sparing with intact retinal layers, while SD-OCT at the mid-periphery, through the lesion (e, f), demonstrates striking transmural atrophy with choroidal involvement. Reproduced with permission from [187]. Copyright© 2016 American Medical Association. All rights reserved
Fig. 15 Multi-modal imaging of didanosine-induced (DDI) toxicity. Widefield FAF (a, b) demonstrated diffuse, bilateral midperipheral areas of well-circumscribed hypo-autofluoresence secondary to DDI toxicity. SD-OCT through the fovea (c, d) reveals macular sparing with intact retinal layers, while SD-OCT at the mid-periphery, through the lesion (e, f), demonstrates striking transmural atrophy with choroidal involvement. Reproduced with permission from [187]. Copyright© 2016 American Medical Association. All rights reservedCC BY · PubMed Central

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Research works printed but not linked: 2

  1. Park SP, Siringo FS, Pensec N, et al. Comparison of fundus autofluorescence between fundus camera and confocal scanning laser ophthalmoscope-based systems. Ophthalmic Surgery Lasers Imaging Retina. 2013;44(6):536–43. · DOI
  2. Espina M, Barteselli G, Ma F, et al. Noncontact ultra-wide field lens system by Heidelberg spectralis. Invest Ophthalmol Vis Sci. 2014;55(13):1615.

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Metadata

Authors
Yung, M., Klufas, M. A., & Sarraf, D.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Sarraf, David
ORCID
Venue
International Journal of Retina and Vitreous
Publisher
Springer Science and Business Media LLC
Published
2016-04-08
Volume
2
Issue
1
Pages
12-12
ISSN
2056-9920 (ISSN-L)
DOI
10.1186/s40942-016-0035-x
PMC
PMC5088473
OpenAlex
W2329521208
Cited by
236
References
198
Citations by year
2026: 15 · 2025: 23 · 2024: 22 · 2023: 20 · 2022: 29 · 2021: 40 · 2020: 31 · 2019: 24 · 2018: 22 · 2017: 8 · 2016: 1
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • International Journal of Retina and Vitreous (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Regeneron Pharmaceuticals
  • Genentech
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
  • Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
Keywords
fundus autofluorescence, lipofuscin, retinal pigment epithelium, age-related macular degeneration, macular dystrophy, retinitis pigmentosa, white dot syndromes, ultra-widefield imaging, confocal scanning laser ophthalmoscopy, genotype-phenotype correlation

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