Investigative Ophthalmology & Visual Science Cover Image for Volume 59, Issue 9
July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Phenotypic heterogeneity of retinal degenerations caused by mutations in CRX examined by multimodal clinical imaging including adaptive optics retinal camera
Author Affiliations & Notes
  • Katarina Stingl
    Center for Ophthalmology, Tübingen, Germany
  • Laura Kuehlewein
    Center for Ophthalmology, Tübingen, Germany
  • Melanie Kempf
    Center for Ophthalmology, Tübingen, Germany
  • Francoise Sadler
    Center for Ophthalmology, Tübingen, Germany
  • Fadi Nasser
    Center for Ophthalmology, Tübingen, Germany
  • Bernd Wissinger
    Center for Ophthalmology, Tübingen, Germany
  • Susanne Kohl
    Center for Ophthalmology, Tübingen, Germany
  • Nicole Weisschuh
    Center for Ophthalmology, Tübingen, Germany
  • Marius Ueffing
    Center for Ophthalmology, Tübingen, Germany
  • Eberhart Zrenner
    Center for Ophthalmology, Tübingen, Germany
  • Footnotes
    Commercial Relationships   Katarina Stingl, None; Laura Kuehlewein, None; Melanie Kempf, None; Francoise Sadler, None; Fadi Nasser, None; Bernd Wissinger, None; Susanne Kohl, None; Nicole Weisschuh, None; Marius Ueffing, None; Eberhart Zrenner, None
  • Footnotes
    Support  CURETINA Grant of the Medical Faculty, University of Tübingen, Germany
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1516. doi:
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      Katarina Stingl, Laura Kuehlewein, Melanie Kempf, Francoise Sadler, Fadi Nasser, Bernd Wissinger, Susanne Kohl, Nicole Weisschuh, Marius Ueffing, Eberhart Zrenner; Phenotypic heterogeneity of retinal degenerations caused by mutations in CRX examined by multimodal clinical imaging including adaptive optics retinal camera. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1516.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinal dystrophies associated with autosomal dominant CRX mutations are known to show strong phenotypical variability. The cone–rod homeobox gene (CRX) encodes a transcription factor for the photoreceptor development and maintenance and its mutations can cause autosomal recessive or dominant inherited disease, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), macular dystrophy (MD), cone dystrophy (CD) or cone-rod dystrophy (CORD). We assessed retinal imaging of these diseases with adaptive optics imaging.

Methods : We examined 9 patients from 4 independent families carrying heterozygous dominant acting CRX mutations (6 males, 3 females, mean age 44.9, range 26-59 years). The patients have been followed up for up to 11 years. Five patients had CORD, two CD, one MD and one RP. All patients were examined by standard functional diagnostics and multimodal imaging including spectral domain optical coherence tomography (OCT), fundus autofluorescence (FAF) and adaptive optics (AO) using the rtx1 camera (Imagine Eyes, Paris).

Results : Patients with CORD, CD as well as MD presented with a clear central atrophy zone on fundus examination except for three youngest patients who were asymptomatic or very mildly affected. OCT and FAF showed central atrophy, and all CORD, CD, and MD patients had a clear hyperfluorescent ring on the margins of the lesion (Fig. 1), except for the two oldest ones with end-stage disease and the youngest, asymptomatic, one. The patient with RP had mild bone spiculae in the mid periphery. AO showed similar patterns of foveal and perifoveal cone mosaic reduction especially in early stages with increased foveal cone visibility and altered perifoveal photoreceptor mosaic (Fig. 2).

Conclusions : Despite phenotypic heterogeneity associated with dominant CRX mutations common patterns of degeneration are visible with multimodal clinical imaging. Adaptive optics retinal imaging can assist in diagnosing early stages retinal dystrophies.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Macula of a patient with CD with the hyperfluorescent ring

Macula of a patient with CD with the hyperfluorescent ring

 

A: AO imaging of an early stage of a CRX-related macular dystrophy showing an altered foveal image with reduced cone density and a perifoveal blurred zone, which correlates to atrophy of cone outer segments on OCT. B: Foveal image of a healthy retina

A: AO imaging of an early stage of a CRX-related macular dystrophy showing an altered foveal image with reduced cone density and a perifoveal blurred zone, which correlates to atrophy of cone outer segments on OCT. B: Foveal image of a healthy retina

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