Lipofuscin and autofluorescence metrics in progressive STGD.
OBJECTIVE
To evaluate Stargardt disease (STGD) progression and relative lipofuscin levels via autofluorescence image analysis.


METHODS
The relationship between focally increased autofluorescence (FIAF), geographic atrophy (GA) and focally decreased autofluorescence (FDAF) was analyzed in serial, registered autofluorescence (AF) scans of 10 patients with STGD (20 eyes, 40 scans; mean follow-up, 2.0 years) using automated techniques.


RESULTS
GA progressed uniformly in a transition zone with minimal FIAF. Only 4.3% of FIAF progressed to GA or FDAF, despite significant progression of GA (median 30%/year) and FDAF (mean, 29%/year). As a spatial predictor, the mean chance of FIAF for progression to FDAF was 4.3% +/- 4.4%, significantly less than that of random areas (6.7% +/- 4.0%, P = 0.029, Mann-Whitney test). In the seven eyes with GA, the mean chance of FIAF in the transition zone for transition to GA was 12% +/- 8.9%, significantly less than that of random areas (33% +/- 3.6%, P = 0.026, Mann-Whitney test).


CONCLUSIONS
Autofluorescent flecks and FIAF deposits with AF levels elevated above the initial macular background were less likely in the short term (2 years) to transform to GA and FDAF (AF levels below the final background) than random areas, suggesting additional mechanisms beyond direct lipofuscin toxicity. FIAF/FDAF levels were observed to fluctuate, with focal remodeling of FIAF and FDAF, or rarely, even transition of FDAF to FIAF. FDAF tended to develop, not coincident with, but adjacent to initial FIAF. Because AF identifies these characteristic biological markers so specifically, autofluorescence metrics merit consideration in the study of STGD.
Smith
R Theodore
RT
Department of Ophthalmology, Columbia University, New York, NY 10032, USA.
Gomes
Nuno L
NL
Barile
Gaetano
G
Busuioc
Mihai
M
Lee
Noah
N
Laine
Andrew
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002648:Child; D018450:Disease Progression; D005260:Female; D005453:Fluorescence; D005838:Genotype; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism*; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D009896:Optic Atrophy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011237:Predictive Value of Tests; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D008062:Lipofuscin