Background and Purpose—: Our aim was to evaluate the risk of subsequent stroke development after retinal artery occlusion (RAO). Methods—: National registry data were collected from the Korean National Health Insurance Service, comprised 1 025 340 random subjects. Patients diagnosed with RAO in 2002 and 2003 were excluded. The RAO group was composed of patients with an initial diagnosis of either central or other RAO between January 2004 and December 2013 (n=401). The comparison group was composed of randomly selected patients (5 per RAO patient; n=2003) who were matched to the RAO group according to sociodemographic factors and year of RAO diagnosis. Each sampled patient was tracked until 2013. Cox proportional hazard regression was used. Results—: Stroke occurred in 15.0% of the RAO group and in 8.0% of the comparison group ( P < 0.001). RAO was associated with an increased risk of stroke occurrence (hazard ratio, 1.78; 95% confidence interval, 1.32–2.41). The magnitude of the RAO effect for stroke was larger among younger adults aged <65 years (hazard ratio, 3.11) than older adults aged ≥65 years (hazard ratio, 1.26). However, the risk of subsequent stroke was significantly increased in older adults aged ≥65 years at the 4-year follow-up (hazard ratio, 1.58; 95% confidence interval, 1.01–2.48). Conclusions—: RAO was significantly associated with subsequent stroke after adjusting for comorbidities and sociodemographic factors. These findings are limited by uncontrolled confounding factors and need to be replicated by other observational studies.

To characterise the genotypic and phenotypic spectrum of foveal hypoplasia (FH) Multi-centre, observational study 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR or achromatopsia (ACHM) from twelve centres in nine countries (n=523), or, extracted from publicly available datasets from previously reported literature (n=384). Individuals with a confirmed molecular diagnosis and availability of foveal optical coherence tomography (OCT) scans were identified from twelve centres or from the literature, between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCTs. Grade of FH, presence or absence of photoreceptor specialisation (PRS+ vs PRS−), molecular diagnosis and visual acuity (VA). The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%) and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of ACHM cases. Atypical FH in ACHM had significantly worse VA compared to typical FH (p<0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (X²=60.4, p<0.0001). All SLC38A8 cases were PRS− (p=0.003), while all FRMD7 cases were PRS+ (p<0.0001). Analysis of albinism sub-types revealed a significant difference in the grade of FH (X²=31.4, p<0.0001) and VA (p=0.0003) between oculocutaneous albinism (OCA) compared to ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). OA and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (p<0.0001) in VA between FRMD7 variants compared to other diagnoses associated with FH. We characterised the phenotypic and genotypic spectrum of FH. Atypical FH is associated with much worse prognosis compared to all other forms of FH. In typical FH, our data suggests that arrested retinal development occurs earlier in SLC38A8, OA, HPS and AHR variants and much later in FRMD7 variants. The defined time-period of foveal developmental arrest for OCA and PAX6 variants appears to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and also have significant prognostic and diagnostic value.

Infantile nystagmus syndrome (INS) is a heterogeneous disorder characterized by continuous oscillation of the eyes with variable visual acuity. Infantile nystagmus syndrome is an important clinical diagnosis because nystagmus is a common presenting sign of many ocular, neurologic, and systemic diseases.¹ Nystagmus can be associated with low vision in early infancy owing to several causes, such as Leber congenital amaurosis (LCA), PAX6 (OMIM 607108)–related phenotypes, or albinism, which makes the differential diagnosis of INS more complex. Furthermore, ophthalmologists can miss subtle retinal abnormalities because continually oscillating eyes hinder the performance of detailed clinical examination. Therefore, meticulous clinical workups using optical coherence tomography (OCT), visual evoked potential, and electroretinography (ERG), are important to differentiate underlying causes of nystagmus. However, results of electrophysiological testing are often inconclusive in pediatric patients. In addition, young children often have been deemed unsuitable for conventional tabletop OCT.

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, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized 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 specialization 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.