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Tomas S Aleman, Katherine E Uyhazi, Leona Serrano, Scott J Bowman, Denise J Pearson, Albert M Maguire, Jean Bennett; Early Structural and Functional Abnormalities in Leber Congenital Amaurosis Caused by Mutations in RDH12. Invest. Ophthalmol. Vis. Sci. 2018;59(9):46. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the retinal structure and function of a relatively large group of pediatric patients with Leber congenital amaurosis (LCA) caused by mutations in the RDH12 gene.
Twenty patients from 13 families (ages 2-17 years) with RDH12-LCA underwent a complete ophthalmic exam. Imaging was performed with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance. Visual thresholds were measured with automated static perimetry and/or chromatic full-field sensitivity testing (FST) complemented by quantitation of the dark-adapted, chromatic, transient pupillary light reflex (TPLR).
When measurable, visual acuity ranged from light-perception to 20/40. Early parafoveal depigmentation or atrophic maculopathies accompanied by midperipheral intraretinal pigment migration dominated the fundus appearance. SD-OCT showed early foveal thinning in all patients with detectable but thinned outer nuclear layer (ONL) at greater eccentricities from the fovea into the pericentral and peripapillary retina. Photoreceptor outer segment (POS) signals were only detectable in small pockets within the central retina. Measurable kinetic visual fields were limited to small (<5-10°) central islands of vision. Electroretinograms were reported as undetectable. FST sensitivities to a 467 nm stimulus were rod-mediated and reduced on average by ~2.5 log units. Thinned but detectable ONL in the central retina colocalized with severely reduced to non-detectable sensitivities. TPLR provided objective confirmation of the psychophysically measured abnormalities.
Early-onset, retina-wide disease with particularly severe central retinal abnormalities associated with detectable peripheral rod photoreceptor function in RDH12-LCA supports a pattern consistent with an early-onset cone-rod dystrophy. Severely abnormal POS but detectable ONL in the pericentral and peripapillary retina suggests these regions may be the targets for gene augmentation as a therapy for this condition.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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