Visual Field Deficits in Albinism in Comparison to Idiopathic Infantile Nystagmus

Purpose: This is the first systematic comparison of visual field (VF) deficits in people with albinism (PwA) and idiopathic infantile nystagmus (PwIIN) using static perimetry. We also compare best-corrected visual acuity (BCVA) and optical coherence tomography measures of the fovea, parafovea, and circumpapillary retinal nerve fiber layer in PwA. Methods: VF testing was performed on 62 PwA and 36 PwIIN using a Humphrey Field Analyzer (SITA FAST 24-2). Mean detection thresholds for each eye were calculated, along with quadrants and central measures. Retinal layers were manually segmented in the macular region. Results: Mean detection thresholds were significantly lower than normative values for PwA (−3.10 ± 1.67 dB, P Conclusions: Clear peripheral and central VF deficits exist in PwA and PwIIN, and static VF results need to be interpreted with caution clinically. Since PwA exhibit considerably lower detection thresholds compared to PwIIN, VF defects are unlikely to be due to nystagmus in PwA. In addition to horizontal VF asymmetry, PwA exhibit both vertical and interocular asymmetries, which needs further exploration.</p

Longitudinal Evaluation of Changes in Retinal Architecture Using Optical Coherence Tomography in Achromatopsia

PURPOSE. This prospective study investigates longitudinal changes in retinal structure in patients with achromatopsia (ACHM) using optical coherence tomography (OCT).  METHODS. Seventeen patients (five adults, 12 children) with genetically confirmed CNGA3- or CNGB3-associated ACHM underwent ocular examination and OCT over a follow-up period of between 2 and 9.33 years (mean = 5.7 years). Foveal tomograms were qualitatively graded and were segmented for quantitative analysis: central macular thickness (CMt), outer nuclear layer thickness (ONLt), and size of the foveal hyporeflective zone (vertical HRZ thickness: HRZt and horizontal HRZ width: HRZw) were measured. Data were analyzed using linear mixed regression models. Both age and visit were included into the models, to explore the possibility that the rate of disease progression depends on patient age. RESULTS. Fifteen of 17 patients (88%) showed longitudinal changes in retinal structure over the follow-up period. The most common patterns of progression was development of ellipsoid zone (EZ) disruption and HRZ. There was a significant increase in HRZt (P = 0.01) and HRZw (P = 0.001) between visits and no significant change in CMt and ONLt. Retinal parameters showed no difference in changes by genetic mutation (CNGA3 (n = 11), CNGB3 (n = 6)).  CONCLUSIONS. This study demonstrates clear longitudinal changes in foveal structure mainly in children, but also in adults with ACHM, over a long follow-up period. The longitudinal foveal changes suggest that treatment at an earlier age should be favored.</p

ERG Responses in Albinism, Idiopathic Infantile Nystagmus, and Controls

PurposeOur primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses.MethodsDilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings.ResultsFor the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P ConclusionsAge-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region

ERG Responses in Albinism, Idiopathic Infantile Nystagmus, and Controls

PurposeOur primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses.MethodsDilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings.ResultsFor the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P ConclusionsAge-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region

SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialisation.

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