Fundus autofluorescence and progression of age-related macular degeneration.

Fundus autofluorescence imaging is an imaging method that provides additional information compared to conventional imaging techniques. It permits to topographically map lipofuscin distribution of the retinal pigment epithelial cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal compartment of retinal pigment epithelium cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases including age-related macular degeneration (AMD). This comprehensive review contains an introduction in fundus autofluorescence imaging, including basic considerations, the origin of the signal, different imaging methods, and a brief overview of fundus autofluorescence findings in normal subjects. Furthermore, it summarizes cross-sectional and longitudinal fundus autofluorescence findings in patients with AMD, addresses the pathophysiological significance of increased fundus autofluorescence, and characterizes different fundus autofluorescence phenotypes as well as fundus autofluorescence alterations with disease progression.

[1]  D. Schweitzer,et al.  Retinal pigment epithelium cell damage by A2-E and its photo-derivatives. , 2006, Molecular vision.

[2]  J. Weiter,et al.  Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. , 1989, Investigative ophthalmology & visual science.

[3]  P. Walter,et al.  Fundus near infrared fluorescence correlates with fundus near infrared reflectance. , 2006, Investigative ophthalmology & visual science.

[4]  M. Katz Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration. , 2002, Archives of gerontology and geriatrics.

[5]  P. D. de Jong,et al.  Cigarette smoking and age-related macular degeneration in the EUREYE Study. , 2007, Ophthalmology.

[6]  R. Hilgers,et al.  Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study. , 2002, American journal of ophthalmology.

[7]  F W Fitzke,et al.  Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. , 1997, Investigative ophthalmology & visual science.

[8]  E. Berman,et al.  Lipofuscin of human retinal pigment epithelium. , 1980, American journal of ophthalmology.

[9]  John C. Hwang,et al.  Predictive value of fundus autofluorescence for development of geographic atrophy in age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[10]  A. Hofman,et al.  REVIEW: Epidemiology of age-related maculopathy: a review , 2003, European Journal of Epidemiology.

[11]  Noemi Lois,et al.  Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss. , 2002, American journal of ophthalmology.

[12]  J. Weiter,et al.  CELL LOSS IN THE AGING RETINA , 1989 .

[13]  F. Delori Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus. , 1994, Applied Optics.

[14]  C Bellman,et al.  Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. , 2001, Investigative ophthalmology & visual science.

[15]  A. Bird,et al.  Distribution of pigment epithelium autofluorescence in retinal disease state recorded in vivo and its change over time , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[16]  J. Dreyhaupt,et al.  Modelling the Natural History of Geographic Atrophy in Patients with Age-Related Macular Degeneration , 2005, Ophthalmic epidemiology.

[17]  R. Radu,et al.  Characterization of Native Retinal Fluorophores Involved in Biosynthesis of A2E and Lipofuscin-associated Retinopathies* , 2006, Journal of Biological Chemistry.

[18]  F W Fitzke,et al.  Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. , 1995, The British journal of ophthalmology.

[19]  Sebastian Wolf,et al.  Changes in fundus autofluorescence in patients with age-related maculopathy. Correlation to visual function: a prospective study , 2003, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  R. Spaide,et al.  Fundus autofluorescence and central serous chorioretinopathy. , 2005, Ophthalmology.

[21]  A Hofman,et al.  Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study. , 1998, Archives of ophthalmology.

[22]  A. Bird,et al.  Autofluorescence Imaging with the Fundus Camera , 2007 .

[23]  C. Keilhauer,et al.  Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration , 2005, British Journal of Ophthalmology.

[24]  R Theodore Smith,et al.  Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[25]  Michael D. Ober,et al.  Autofluorescence and retinal pigment epithelial atrophy after subretinal hemorrhage. , 2006, Retina.

[26]  C. Eldred Questioning the nature of the fluorophores in age pigments , 1987 .

[27]  M. Killingsworth,et al.  Evolution of geographic atrophy of the retinal pigment epithelium , 1988, Eye.

[28]  B. Kirchhof,et al.  Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration. , 2006, American journal of ophthalmology.

[29]  Usha Chakravarthy,et al.  Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). , 2006, Archives of ophthalmology.

[30]  C K Dorey,et al.  In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. , 1995, Investigative ophthalmology & visual science.

[31]  F. Kruse,et al.  Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. , 1999, Investigative ophthalmology & visual science.

[32]  U. Brunk,et al.  Accumulation of lipofuscin within retinal pigment epithelial cells results in enhanced sensitivity to photo-oxidation. , 1995, Gerontology.

[33]  P. Maguire,et al.  Geographic atrophy of the retinal pigment epithelium. , 1986, American journal of ophthalmology.

[34]  Paul Mitchell,et al.  Ten-year incidence and progression of age-related maculopathy: the blue Mountains Eye Study. , 2007, Ophthalmology.

[35]  Usha Chakravarthy,et al.  Fundus autofluorescence in age-related macular degeneration: an epiphenomenon? , 2006, Investigative ophthalmology & visual science.

[36]  R. Webb,et al.  Confocal scanning laser ophthalmoscope. , 1987, Applied optics.

[37]  J. Roider,et al.  Autologous retinal pigment epithelium–choroid sheet transplantation in age related macular degeneration: morphological and functional results , 2006, British Journal of Ophthalmology.

[38]  Jens Dreyhaupt,et al.  Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD. , 2006, Investigative ophthalmology & visual science.

[39]  M. Boulton,et al.  RPE lipofuscin and its role in retinal pathobiology. , 2005, Experimental eye research.

[40]  F. Holz,et al.  Analysis of digital scanning laser ophthalmoscopy fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration , 2002, Graefe's Archive for Clinical and Experimental Ophthalmology.

[41]  B. Lorenz,et al.  Fundus autofluorescence in children and teenagers with hereditary retinal diseases , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[42]  Sonia H Yoo,et al.  Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. , 2003, Survey of ophthalmology.

[43]  M. Hogan Role of the retinal pigment epithelium in macular disease. , 1972, Transactions - American Academy of Ophthalmology and Otolaryngology. American Academy of Ophthalmology and Otolaryngology.

[44]  C. Regillo SYMMETRY OF BILATERAL LESIONS IN GEOGRAPHIC ATROPHY IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION , 2002 .

[45]  R. C. Petersen American national standard for the safe use of optical fiber communications systems utilizing laser diodes and LED sources, ANSI Z136.1-1997 , 1997 .

[46]  S. Davies,et al.  Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. , 2000, Investigative ophthalmology & visual science.

[47]  Richard F Spaide,et al.  Fundus autofluorescence and age-related macular degeneration. , 2003, Ophthalmology.

[48]  Frank G Holz,et al.  DIGITAL SIMULTANEOUS FLUORESCEIN AND INDOCYANINE GREEN ANGIOGRAPHY, AUTOFLUORESCENCE, AND RED-FREE IMAGING WITH A SOLID-STATE LASER-BASED CONFOCAL SCANNING LASER OPHTHALMOSCOPE , 2005, Retina.

[49]  C. Bellmann,et al.  [Topography of fundus autofluorescence with a new confocal scanning laser ophthalmoscope]. , 1997, Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft.

[50]  Steffen Schmitz-Valckenberg,et al.  Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:Sapphire laser. , 2006, Investigative ophthalmology & visual science.

[51]  W R Green,et al.  Age-related Macular Degeneration Histopathologic Studies: The 1992 Lorenz E. Zimmerman Lecture , 1993, Ophthalmology.

[52]  C. J. Blair,et al.  Geographic atrophy of the retinal pigment epithelium. A manifestation of senile macular degeneration. , 1975, Archives of ophthalmology.

[53]  M. Katz,et al.  Fluorophores of the human retinal pigment epithelium: separation and spectral characterization. , 1988, Experimental eye research.

[54]  Ronald Klein,et al.  Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. , 2007, Ophthalmology.

[55]  F. Delori,et al.  Near-infrared autofluorescence imaging of the fundus: visualization of ocular melanin. , 2006, Investigative ophthalmology & visual science.

[56]  M. Boulton,et al.  The role of the retinal pigment epithelium: Topographical variation and ageing changes , 2001, Eye.

[57]  A. Bird,et al.  Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration. , 2002, Ophthalmology.

[58]  S. Sarks,et al.  Ageing and degeneration in the macular region: a clinico-pathological study. , 1976, The British journal of ophthalmology.

[59]  C K Dorey,et al.  Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. , 2001, Investigative ophthalmology & visual science.

[60]  C K Dorey,et al.  Autofluorescence distribution associated with drusen in age-related macular degeneration. , 2000, Investigative ophthalmology & visual science.

[61]  G S Rubin,et al.  Fundus autofluorescence imaging compared with different confocal scanning laser ophthalmoscopes , 2002, The British journal of ophthalmology.

[62]  C. Bellmann,et al.  Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[63]  C. Keilhauer,et al.  IMAGING OF RETINAL AUTOFLUORESCENCE IN PATIENTS WITH AGE‐RELATED MACULAR DEGENERATION , 1997, Retina.

[64]  A. Bird,et al.  Age-related macular disease. , 1996, The British journal of ophthalmology.

[65]  J. Weiter,et al.  The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. , 1978, Investigative ophthalmology & visual science.

[66]  Albert Hofman,et al.  Epidemiology of age-related maculopathy: a review. , 2003, European journal of epidemiology.

[67]  J. Kopitz,et al.  Lipids and lipid peroxidation products in the pathogenesis of age-related macular degeneration. , 2004, Biochimie.

[68]  T. Hashimoto,et al.  Confocal scanning laser microscopic findings of excised choroidal neovascular membranes of age-related macular degeneration and their comparison with the clinical features. , 1999, Japanese journal of ophthalmology.

[69]  J. Weiter,et al.  Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. , 1986, Investigative ophthalmology & visual science.

[70]  E. Bouzas,et al.  Fundus autofluorescence imaging in serous and drusenoid pigment epithelial detachments associated with age-related macular degeneration. , 2005, American journal of ophthalmology.

[71]  Joe G Hollyfield,et al.  Spectral profiling of autofluorescence associated with lipofuscin, Bruch's Membrane, and sub-RPE deposits in normal and AMD eyes. , 2002, Investigative ophthalmology & visual science.

[72]  E. Choromokos,et al.  Pseudofluorescence--a problem in interpretation of fluorescein angiograms. , 1970, American journal of ophthalmology.

[73]  Y. Jang,et al.  Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium , 2006, Proceedings of the National Academy of Sciences.

[74]  H Schatz,et al.  Atrophic macular degeneration. Rate of spread of geographic atrophy and visual loss. , 1989, Ophthalmology.

[75]  U. Brunk,et al.  Oxidative stress, accumulation of biological 'garbage', and aging. , 2006, Antioxidants & redox signaling.

[76]  A. Bird,et al.  Association of drusen deposition with choroidal intercapillary pillars in the aging human eye. , 2004, Investigative ophthalmology & visual science.

[77]  K. Kitagawa,et al.  In vivo quantitation of autofluorescence in human retinal pigment epithelium. , 1989, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde.

[78]  U. Mansmann,et al.  Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO) , 2005, BMC ophthalmology.

[79]  R. Klein,et al.  Pathogenesis of lesions in late age-related macular disease. , 2004, American journal of ophthalmology.

[80]  A. Bird,et al.  Long-term results of submacular surgery combined with macular translocation of the retinal pigment epithelium in neovascular age-related macular degeneration. , 2005, Ophthalmology.

[81]  K. Nakanishi,et al.  The Biosynthesis of A2E, a Fluorophore of Aging Retina, Involves the Formation of the Precursor, A2-PE, in the Photoreceptor Outer Segment Membrane* , 2000, The Journal of Biological Chemistry.

[82]  J. Kopitz,et al.  Inhibition of the ATP‐driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2‐E may contribute to the pathogenesis of age‐related macular degeneration , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[83]  S. Sarks,et al.  Drusen patterns predisposing to geographic atrophy of the retinal pigment epithelium. , 1982, Australian journal of ophthalmology.

[84]  Giovanni Staurenghi,et al.  Classification of fundus autofluorescence patterns in early age-related macular disease. , 2005, Investigative ophthalmology & visual science.

[85]  E. Bouzas,et al.  Fundus Autofluorescence Imaging Findings in Retinal Pigment Epithelial Tear , 2006, European journal of ophthalmology.

[86]  John D Simon,et al.  A2E: A Component of Ocular Lipofuscin¶ , 2004, Photochemistry and photobiology.

[87]  Jens Dreyhaupt,et al.  Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. , 2007, American journal of ophthalmology.

[88]  J S Sunness,et al.  Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. , 1999, Ophthalmology.

[89]  F. Holz,et al.  Topographie der Fundusautofluoreszenz mit einem neuen konfokalen Scanning-Laser-Ophthalmoskop , 1997, Der Ophthalmologe.

[90]  Usha Chakravarthy,et al.  Age related macular degeneration , 2003, BMJ : British Medical Journal.

[91]  Noemi Lois,et al.  Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease , 2000, The British journal of ophthalmology.

[92]  R. Klein,et al.  Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. , 2003, Ophthalmology.

[93]  G. Eldred,et al.  Retinal age pigments generated by self-assembling lysosomotropic detergents , 1993, Nature.

[94]  T. Peto,et al.  Autofluorescence imaging of choroidal neovascularization due to age-related macular degeneration. , 2005, Archives of ophthalmology.

[95]  A C Bird,et al.  The relationships of age changes in retinal pigment epithelium and Bruch's membrane. , 1999, Investigative ophthalmology & visual science.

[96]  T. Peto,et al.  Autofluorescence imaging in age-related macular degeneration complicated by choroidal neovascularization: a prospective study. , 2008, Ophthalmology.

[97]  A. Bird,et al.  Reproducibility of fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope , 1999, The British journal of ophthalmology.

[98]  J. Dreyhaupt,et al.  Fundus autofluorescence and fundus perimetry in the junctional zone of geographic atrophy in patients with age-related macular degeneration. , 2004, Investigative ophthalmology & visual science.

[99]  A. Bird,et al.  Photopic and scotopic fine matrix mapping of retinal areas of increased fundus autofluorescence in patients with age-related maculopathy. , 2004, Investigative ophthalmology & visual science.

[100]  M. Killingsworth,et al.  RETICULAR PSEUDODRUSEN: A Risk Factor in Age-Related Maculopathy , 1995, Retina.

[101]  F W Fitzke,et al.  In vivo fundus autofluorescence in macular dystrophies. , 1997, Archives of ophthalmology.