Quantitative Fundus Autofluorescence in Recessive Stargardt Disease

Tomas Burke

Tobias Duncker

Russell Woods

Jonathan Greenberg

^{Department of Ophthalmology and Columbia University, New York, New York, United States}

^{Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States}

^{Department of Pathology and Cell Biology, Columbia University, New York, New York, United States}

^{Department of Ophthalmology, New York University School of Medicine, New York, New York, United States}

Current affiliation: *Department of Ophthalmology, Royal United Hospital, Bath, United Kingdom.

^{Department of Ophthalmology, New York University Langone Medical Center and School of Medicine, New York, United States.}

Correspondence: François C. Delori, Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA; ude.dravrah.ieem@iroled_siocnarf.

Received 2013 Nov 16; Accepted 2014 Mar 18.

Abstract

Purpose.

To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1).

Methods.

A total of 42 STGD1 patients (ages: 7–52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III.

Results.

Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease.

Conclusions.

Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.

Keywords: ABCA4, lipofuscin, retinal pigment epithelium, scanning laser ophthalmoscope, quantitative fundus autofluorescence, recessive Stargardt disease

Abstract

Acknowledgments

Supported in part by Grants EY021163, EY019861, EY015520, and EY019007 (Core Support for Vision Research) from the National Eye Institute/National Institutes of Health; the Foundation Fighting Blindness (Owings Mills, Maryland, United States); and unrestricted funds from Research to Prevent Blindness (New York, New York) to the Department of Ophthalmology, Columbia University. The authors alone are responsible for the content and writing of the paper.

Disclosure: T.R. Burke, None; T. Duncker, None; R.L. Woods, None; J.P. Greenberg, None; J. Zernant, None; S.H. Tsang, None; R.T. Smith, None; R. Allikmets, None; J.R. Sparrow, None; F.C. Delori, None

Acknowledgments

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