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Disease Boundaries in the Retina of Patients with Usher Syndrome Caused by MYO7A Gene Mutations

¹From the Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania; the ²Department of Pathology, Harvard Medical School, Boston, Massachusetts; and the ³Usher Syndrome Center, Boys Town National Research Hospital, Omaha, Nebraska.

PURPOSE. To study retinal microstructure in Usher Syndrome type 1B (USH1B) caused by MYO7A mutations as a prelude to treatment initiatives.

METHODS. Patients with MYO7A-USH1B (n = 17; ages 5–61) were studied with optical coherence tomography. Retinal laminae across horizontal and vertical meridians were measured. Colocalized visual sensitivity was measured with automated perimetry to enable comparisons of function and structure in the transition zones.

RESULTS. Laminar architecture of the central retina in MYO7A-USH1B ranged from normal to severely abnormal. Within the transition zone between normal and abnormal retina, the first detectable abnormality was an increase in prominence of the OLM (outer limiting membrane). Declining ONL thickness was accompanied by increased thickness of the OPL and normal or increased INL. Undetectable ONL and OPL and hyperthick INL were features of severe laminopathy at further eccentricities into the transition zone. Visual sensitivity in the transition zone declined with the decrease in ONL thickness.

CONCLUSIONS. Patients with MYO7A-USH1B can have regions of structurally and functionally normal retina with definable transitions to severe laminopathy and visual loss. The earliest detectable structural markers of disease may represent Müller glial cell response to photoreceptor stress and apoptosis. Visual losses were predictably related to a decline in ONL thickness. The prospect of focal treatment of MYO7A-USH1B, such as subretinal gene therapy, prompts the need to identify retinal locations that warrant consideration for treatment in early phase trials. The transition zones are candidate sites for treatment, and laminar architecture and visual sensitivity are possible outcomes to assess safety and efficacy.

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