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. 2022 Mar 6;12(3):381.
doi: 10.3390/life12030381.

Kinetics of Heterogeneous Background in Stargardt's Disease over Time

Eduardo Rodríguez-Bocanegra  1   2   3 , Marc Biarnés  1   4 , Míriam Garcia  1   4 , Lucía Lee Ferraro  1   4 , Manuel Dominik Fischer  2   3   5   6 , Jordi Monés  1   4
Affiliations

Kinetics of Heterogeneous Background in Stargardt's Disease over Time

Eduardo Rodríguez-Bocanegra et al. Life (Basel). .

Abstract

Stargardt's disease (STGD1) is caused by mutations in the ABCA4 gene. Different lesions characterised by decreased autofluorescence levels are found in fundus autofluorescence (FAF) from STGD1 patients and could be used as outcome indicators for disease progression. We investigated the fate of foci with reduced autofluorescence (FRA) within the heterogeneous background of STGD1 patients using FAF imaging. Genetically confirmed STGD1 patients presenting heterogeneous background autofluorescence on high-quality FAF images at a minimum of two visits at least 12 months apart were chosen. A grid centred on the fovea was used to define five different zones. Within each zone, five FRA were randomly selected for each eye. The eccentricity of foci was determined at different time points for each patient. Analysis of 175 randomly chosen FRA showed consistent centrifugal displacement over time, most notably in eyes showing areas with definitely decreased autofluorescence. Interestingly, FRA did not leave an area of hypo-autofluorescence on FAF in locations where they were previously located. These findings may help to better understand STGD1 progression, improve FAF interpretation, and shed light on the nature of heterogeneous background.

Keywords: Stargardt’s disease; definitely decreased autofluorescence; foci with reduced autofluorescence; fundus autofluorescence; heterogeneous background; kinetics.

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Conflict of interest statement

The authors declare that they have no conflict of interest. The authors alone are responsible for the content and writing of the paper. E.R.-B. has no financial disclosure. However, M.B. would like to disclosure that he received remuneration from Roche. L.L.F. and M.G. receive remuneration from Novartis and Roche. J.M. receives remuneration from Alcon, Bayer, Genentech, Inc, Iveric Bio, Novartis, Ophthotech, Reneuron and Roche. M.D.F. is on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: Adelphi Values, Advent France Biotechnology, Alphasights, Arctos, Atheneum, Axiom Healthcare Strategies, Biogen, Decision Resources, Dialectica, Frontera Therapeutics, Janssen Research & Development, Navigant, Novartis, Roche, RegenxBio, Sirion, STZeyetrial. M.D.F. is director of Fischer Consulting Limited and holds a patent (50%) on a gene therapy product for X-linked Retinitis Pigmentosa.

Figures

Figure 1
Figure 1
Representative FAF image of a STGD1 patient with heterogeneous background. (a) A grid of five concentric white rings with a radius of 0.75, 1.5, 2.25, 3.0 and 3.75 mm centred on the foveola separated five different zones (Z1–Z5, respectively) in the retina. (b) Magnified image from FAF image (red rectangle) shows the appearance of heterogeneous background and reduced autofluorescence foci or FRA (in blue).
Figure 2
Figure 2
Sequential FAF imaging of an STGD1 patient at different time points. (a–d) The vessel and highlighted FRA at baseline (in red) are in the same position in every image of the sequence in order to appreciate the movement of the FRA in successive follow-up visits (M0, M14, M20 and M38). FAF: fundus autofluorescence; M: Month; STGD1: Stargardt’s disease.
Figure 3
Figure 3
Comparison between kinetics of FRA according to the presence or absence of DDAF lesions. Highlighted FRA at baseline (in red) are always in the same position in order to appreciate the movement of the FRA between two time points. DDAF: definitely decreased fundus autofluorescence; FRA: foci of reduced autofluorescence; M: Month.
Figure 4
Figure 4
Simultaneous visualization of an FRA in FAF and SD-OCT imaging. (a) Reduced autofluorescence focus under the bright green line delimited by two red lines that project on the (b) SD-OCT. (c) Follow-up of FAF image 30 months later. (d) Red lines delimit the same location as in (a-b) from FAF to the corresponding SD-OCT location. FAF: Fundus autofluorescence. ONL: Outer nuclear layer. PR: photoreceptors inner and outer segments. RPE: retinal pigment epithelium. SD-OCT: Spectral-domain optical coherence tomography.
Figure 5
Figure 5
Graphic representation of two hypothetical scenarios to explain movement of FRA within the heterogeneous background. The movement could potentially occur either along with or across the retinal tissue over time. The squares in the red rectangles represent retinal tissue (black: definitely decreased autofluorescence; grey: foci of reduced autofluorescence).
See this image and copyright information in PMC

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