Spectral-domain optical coherence tomography findings in Alström syndrome

ABSTRACT

Background: Alström syndrome is a multi-system recessive disorder caused by mutations in ALMS1 gene. The aim of this study was to characterize morphological retinal changes in Alström patients using spectral-domain optical coherence tomography.

Methods: We studied volunteer patients attending the conference of Alström Syndrome International, a support group for affected families, using hand-held spectral-domain optical coherence tomography (SD-OCT) in an office setting. Patients had a clinical dilated retinal examination. Past medical records were reviewed.

Results: Twenty-two Alström patients (mean age 17 years, range 2–38 years, 12 males) were studied. OCT imaging demonstrated that central macular OCT changes are often mild during the first decade of life and gradually progress, demonstrating disruption of normal retinal architecture, and progressive loss of photoreceptors and retinal pigment epithelium. Other changes found included hyperreflectivities in all retinal layers, severe retinal wrinkling, optic nerve drusen, and vitreoretinal separation. Vision correlated with severity of OCT macular changes (r = 0.89, p = 0.002).

Conclusions: This study reports on OCT findings in a large group of patients with Alström syndrome. We document a panretinal gradual progression of retinal changes, which are often mild during the first years of life. Previously unreported observations include intraretinal opacities, optic nerve drusen, and foveal contour abnormalities. Morphological retinal changes demonstrated by SD-OCT may help in understanding the pathophysiology of the disease and defining strategies for treatment such as gene therapy.

KEYWORDS:

• Alström syndrome
• ocular genetics
• optical coherence tomography

Acknowledgments

During the review of this article for Ophthalmic Genetics, Jan Marshall, the energetic leader of Alström Syndrome International, passed away leaving a legacy of cooperation and collaboration on behalf of all those around the world affected by this disease. Our article is dedicated to her memory and spirit.

We are grateful to the individuals with Alström Syndrome and their families for their participation in this study. We thank Alström Syndrome International (ASI) for providing the opportunity to conduct this study. ASI and Alström Syndrome Canada sponsored the patient genotyping. GD and AVL had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Declaration of interest

DAG is an employee of Bioptigen Inc., the manufacturer of the hand-held OCT instrument used in this study. The remaining authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This work was supported by The Foerderer Fund (AVL), the Robison D. Harley, MD Endowed Chair in Pediatric Ophthalmology and Ocular Genetics (AVL), and National Institutes of Health grant HD036878 (JDM, GBC, JKN). The sponsor or funding organization had no role in the design or conduct of this research.

Additional information

Funding

This work was supported by The Foerderer Fund (AVL), the Robison D. Harley, MD Endowed Chair in Pediatric Ophthalmology and Ocular Genetics (AVL), and National Institutes of Health grant HD036878 (JDM, GBC, JKN). The sponsor or funding organization had no role in the design or conduct of this research.