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Wadih M Zein, Diana X Bharucha-Goebel, Payam Mohassel, Aileen Reghan Foley, Tanya J Lehky, Melissa Waite, Jain S Mina, Brett G Jeffrey, Brian Patrick Brooks, Carsten Bonnemann; Ophthalmic Manifestations of Giant Axonal Neuropathy (GAN): Towards Establishing Visual Function / Optic Atrophy Assessments as a Secondary Outcome Measure in an Ongoing Intrathecal Gene Transfer Trial. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5995.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the ophthalmic manifestations of GAN, a rare autosomal recessive neurodegenerative disease caused by mutations in the Gigaxonin gene.To investigate the potential utility of visual function measures as a secondary outcome measure for a GAN gene transfer clinical trial (NCT02362438).
Seventeen children with GAN underwent comprehensive ophthalmic evaluation as part of a natural history protocol at the National Institutes of Health (NCT01568658). Age at initial ophthalmic exam ranged from 4.5 to 15 years (median 9.0 yrs). Visual acuity, visual field, color vision, and optical coherence tomography (OCT) data was analyzed. Correlation with systemic measures of disease severity such as the Motor Function Measure (MFM32) were undertaken.
Visual acuity ranged from 20/20 to 20/320 (logMAR 0.0 to 1.2; Mean ± SD 0.4 ± 0.3 logMAR). Visual fields were obtained in 12 patients and showed a deficit in 8/12 (66%). Color vision was abnormal in 7/17 patients (41%). Anatomic or functional evidence of optic atrophy was ascertained in 10/17 patients (59%). Subtle optic nerve pallor with borderline retinal nerve fiber layer (RNFL) thickness and normal visual function was noted in 5/17 patients (29%). Normal optic nerve exam was present in two GAN patients (12%). Optic nerve OCT showed an average RNFL thickness of 72.3 ± 18.0µm OD and 70.7 ± 17.2µm OS (literature mean for this age group 97.2 µm, first percentile 75.1 µm). RNFL thickness correlated well with disease severity measured by MFM32 (Spearman r 0.76, R-square 0.57). Average macular ganglion cell analysis (GCA) thickness was 63.6 ± 12.0µm OD and 64.5 ± 10.2µm OS. Older patients had thinner RNFL and GCA measurements. Other ophthalmic features noted in this cohort included strabismus (5/17, 29%), nystagmus (10/17, 59%), hypometric saccades, and lagophthalmous.
Optic atrophy is a common manifestation of GAN. Optic nerve OCT parameters correlate well with disease severity. Regular ophthalmic exam and OCT are recommended for GAN patients. Visual function measures and electrophysiologic / anatomic methods focused on assessing severity of optic atrophy can potentially serve as a secondary outcome measure in GAN treatment trials (e.g. the currently recruiting intrathecal gene transfer study NCT02362438).
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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