Original article
Progression of Geographic Atrophy and Impact of Fundus Autofluorescence Patterns in Age-related Macular Degeneration

https://doi.org/10.1016/j.ajo.2006.11.041Get rights and content

Purpose

To test if fundus autofluorescence (FAF) patterns around geographic atrophy (GA) have an impact on GA progression rates over time in atrophic age-related macular degeneration (AMD).

Design

Prospective longitudinal multicenter natural history study.

Methods

Standardized digital FAF images were obtained from 195 eyes of 129 patients with GA using confocal scanning laser ophthalmoscopy (excitation 488 nm, emission >500 nm). Areas of GA were quantified and patterns of abnormal FAF in the junctional zone were classified. Repeated FAF images were obtained over a median follow-up period of 1.80 years (interquartile range [IQR], 1.28 to 3.34).

Results

Areas of GA (median, 7.04 mm2 at baseline; IQR, 3.12 to 10.0) showed a median enlargement of 1.52 mm2/year (IQR, 0.81 to 2.33). Progression rates in eyes with the banded (median 1.81 mm2/year) and the diffuse FAF pattern (1.77 mm2/year) were significantly higher compared to eyes without FAF abnormalities (0.38 mm2/year) and focal FAF patterns (0.81 mm2/year, P < .0001). Within the group of the diffuse pattern, eyes with a diffuse trickling pattern could be identified that exhibited an even higher spread rate (median 3.02 mm2/year) compared to the other diffuse types (1.67 mm2/year, P = .001).

Conclusions

The results indicate that distinct phenotypic FAF patterns have an impact on disease progression in eyes with atrophic AMD and may therefore serve as prognostic determinants. The findings underscore the relevance of FAF imaging and the pathogenetic role of excessive retinal pigment epithelium (RPE) lipofuscin (LF) accumulation in GA. Natural history data and identification of high-risk characteristics will be helpful to design interventional studies aiming at slowing the spread of atrophy.

Section snippets

Patients and methods

Patients with GA secondary to AMD were included from the longitudinal natural history arm of the multicenter FAM-Study (registration www.clinicaltrials.gov: NCT00393692). The study followed the tenets of the Declaration of Helsinki and was approved by the local Institutional Review Boards and the local ethics committees at the study centers. Informed consent was obtained from each patient after explanation of the nature and possible consequences of the study.

Patients with uni- or multifocal GA

Results

A total of 195 eyes of 129 patients (76 female, 53 male) met the inclusion criteria and were analyzed. Median age at first examination was 73.8 years (interquartile range [IQR], 67.6 to 78.2). Bilateral GA was present in 87 patients; in 66 of those patients, both eyes were included into the study, whereas 42 patients had unilateral atrophies. In three study eyes, a CNV developed during the follow-up period (1.5%). Overall, median follow-up for all eyes was 1.80 years (IQR, 1.28 to 3.34; range,

Discussion

With the advent of digital confocal scanning laser ophthalmoscopy, it has become possible to visualize LF accumulation at the level of the RPE cell monolayer in vivo.19, 20, 21, 35 FAF imaging gives additional information above and beyond conventional imaging tools such as fundus photography, fluorescein angiography, or optical coherence tomography. In a cross-sectional analysis of the FAM-Study, we recently identified various distinct patterns of abnormal elevated FAF in the junctional zone of

Frank G. Holz, MD, is a Professor and Chairman, Department of Ophthalmology, University of Bonn, Germany. He has a particular interest in the pathogenesis and therapy of age-related macular degeneration. A main focus in retinal imaging is fundus autofluorescence imaging using scanning laser ophthalmoscopy. Dr Holz is a founding member of the German priority research program “Age-related Macular Degeneration”, Editor-in-Chief of the organ of the German Ophthalmological Society “Der

References (57)

  • R. van Leeuwen et al.

    Epidemiology of age-related maculopathy: a review

    Eur J Epidemiol

    (2003)
  • D.S. Friedman et al.

    Eye Diseases Prevalence Research GroupPrevalence of age-related macular degeneration in the United States

    Arch Ophthalmol

    (2004)
  • J.S. Sunness

    The natural history of geographic atrophy, the advanced atrophic form of age-related macular degeneration

    Mol Vis

    (1999)
  • F.L. Ferris et al.

    Age-related macular degeneration and blindness due to neovascular maculopathy

    Arch Ophthalmol

    (1984)
  • J.J. Weiter et al.

    Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes

    Invest Ophthalmol Vis Sci

    (1986)
  • S. O’Gorman et al.

    Histopathologic findings in Best’s vitelliform macular dystrophy

    Arch Ophthalmol

    (1988)
  • M. Boulton

    Aging of the retinal pigment epithelium

  • M. Boulton et al.

    The role of the retinal pigment epithelium: topographical variation and aging changes

    Eye

    (2001)
  • F.G. Holz et al.

    Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin

    Invest Ophthalmol Vis Sci

    (1999)
  • F. Schutt et al.

    Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin

    Invest Ophthalmol Vis Sci

    (2000)
  • J.R. Sparrow et al.

    The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells

    Invest Ophthalmol Vis Sci

    (2000)
  • A. von Ruckmann et al.

    Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope

    Invest Ophthalmol Vis Sci

    (1997)
  • A. Bindewald et al.

    Visualization of retinal pigment epithelial (RPE) cells in vivo using digital high resolution confocal scanning laser ophthalmoscopy

    Am J Ophthalmol

    (2004)
  • A. Bindewald et al.

    Fundus autofluorescence imaging

  • J.J. Jorzik et al.

    Digital simultaneous fluorescein and indocyanine green angiography, autofluorescence, and red-free imaging with a solid-state laser-based confocal scanning laser ophthalmoscope

    Retina

    (2005)
  • F.C. Delori et al.

    In vivo fluorescence of the ocular fundus exhibits RPE lipofuscin characteristics

    Invest Ophthalmol Vis Sci

    (1995)
  • F.C. Delori et al.

    Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects

    Invest Ophthalmol Vis Sci

    (2001)
  • F.G. Holz 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

    Graefe’s Arch Clin Exp Ophthalmol

    (1999)
  • Cited by (482)

    • Endpoints for clinical trials in ophthalmology

      2023, Progress in Retinal and Eye Research
    • 10q26 – The enigma in age-related macular degeneration

      2023, Progress in Retinal and Eye Research
    View all citing articles on Scopus

    Frank G. Holz, MD, is a Professor and Chairman, Department of Ophthalmology, University of Bonn, Germany. He has a particular interest in the pathogenesis and therapy of age-related macular degeneration. A main focus in retinal imaging is fundus autofluorescence imaging using scanning laser ophthalmoscopy. Dr Holz is a founding member of the German priority research program “Age-related Macular Degeneration”, Editor-in-Chief of the organ of the German Ophthalmological Society “Der Ophthalmologe”, and president-elect of that society.

    Supplemental Material available at AJO.com.

    View full text