FHONDA (foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis) is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report sixteen novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. 90% of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterised the retinal development in vivo in patients with SLC38A8 mutations using high resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialisation features such as outer segment lengthening implies reduced foveal cone density which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype.

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This study objectively demonstrates the under-reported clinical scenario of head drift during cataract surgery. By manipulating the Eyesi we have shown that eye movements reduce the quality of cataract surgery.