Quantitative measurements of autofluorescence in Stargardt’s disease

Abstract

 

Purpose

 

To obtain quantitative measurements of autofluorescence (qAF) in a cohort of patients with Stargardt’s disease (STGD1).

 

Methods

 

45 patients with a clinical diagnosis of STGD1 and a mean age of 29 years (range: 7-52 years) were studied. AF images were acquired with a confocal scanning laser ophthalmoscope (cSLO) 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, the zero GL, and the magnification, to give quantified autofluorescence (qAF). For each patient, the mean qAF was based on values obtained from 8 circularly arranged segments positioned at an eccentricity of about 7°- 9° (depending on the refractive error). Genotyping of the ABCA4 gene was performed in all patients using the ABCR 700 microarray and direct sequencing.

 

Results

 

qAF levels were significantly increased in 40/45 patients. Differences were more pronounced in younger patients with up to 5 times higher levels than normal controls. Patients carrying the G1916E mutation exhibited less pronounced increases in qAF levels. From the 5 patients without significantly increased qAF levels, 4 carried the G1961E mutation.

 

Conclusions

 

qAF is a novel imaging technique that allows in vivo measurements of lipofuscin. ABCA4 mutations cause significantly increased qAF levels, consistent with previous reports of increased RPE lipofuscin. qAF will help to establish genotype-phenotype correlations and serve as an outcome measure in clinical trials.

 

 

qAF measurements were obtained from 8 circularly arranged segments (outlined in yellow) that were scaled to the distance between the fovea and the edge of the optic disc. The rectangle at the top of the image is the internal fluorescent reference.

 

 

qAF values of STGD1 patients as a function of age. Patients are divided into two groups based on the presence of flecks and/or atrophy in the retinal periphery. Error bars represent the standard deviation of qAF values based on multiple images of each patient. The 95% confidence interval (dashed lines) and mean curve (solid line) of qAF values in normal subjects are indicated.

 

Keywords: 582 ipofuscin • 494 degenerations/dystrophies • 550 imaging/image analysis: clinical