Anterior Chamber Measurements in Healthy Children: A Cross-Sectional Study Using Optical Coherence Tomography

Purpose: To establish anterior chamber measurements in children and investigate the influence of demographic factors on anterior chamber development. Methods: Handheld optical coherence tomography was used to scan the anterior chamber of participants’ eyes, without sedation. Image J was used to generate quantitative anterior chamber measurements, including central corneal thickness (CCT), anterior chamber width, trabecular meshwork length (TML), Schwalbe’s line–angle opening distance (SL-AOD), and trabecular iris surface area (SL-TISA). The average anterior chamber measurements per age group, with 95% prediction intervals, were estimated using fractional polynomial modeling. Mixed regression models were used to evaluate the influence of age, gender, eye, angle, and refractive error variation on anterior chamber measurements. Results: Scans from 223 healthy children (2 days to 15 years of age) and 59 adults (16 to 47 years of age)were included. The anterior chamber width, TML, Schwalbe’s line–angle opening distance, and Schwalbe’s line–trabecular iris surface area significantly increased, whereas CCT decreased with aging (all P 0.05). The temporal TML development was significantly greater than the nasal TML (P < 0.05). CCT development was negatively correlated with refractive power. Conclusions: This novel, non-invasive study describes the postnatal development of anterior chamber in newborn children. Translational Relevance: Our established quantitative measurements have potential clinical use in understanding anterior segment diseases

Restricted Spatial Windows of Visibility in Myalgic Encephalomyelitis (ME).

Myalgic encephalomyelitis (ME) is a devastating disorder marked by debilitating fatigue. It not well understood and its diagnosis is controversial. It is very important therefore that significant clinical features are investigated. Visual symptoms in ME represent a group of distinct, quantifiable, clinical features that could significantly improve diagnosis and provide insights into underlying pathology. The purpose of the present study was therefore to explore the effect of ME on spatial windows of visibility using the spatial contrast sensitivity function. Contrast sensitivity was determined for stationary luminance-defined sinusoidal gratings spanning a five-octave range of spatial frequencies (0.5 to 16 c/deg) in a group of 19 individuals with ME and a group of 19 matched (age, gender) controls. Compared to controls, the ME group exhibited a restricted spatial window of visibility for encoding stimulus contrast. This was characterised principally by a contrast sensitivity deficit at lower spatial frequencies and a narrower bandwidth. Our findings suggest that contrast sensitivity deficits may represent a visual marker of ME, and be indicative of abnormal visual processing at the level of the retina and in the cortical and subcortical visual pathways

Use of Hand-Held Optical Coherence Tomography during Retinopathy of Prematurity (ROP) Screening demonstrates an increased Outer Retina from early Postmenstrual Age in Preterm Infants with ROP.

PurposeTo identify structural markers of active retinopathy of prematurity (ROP) in foveal and parafoveal retinal layers using hand-held optical coherence tomography (HH-OCT).MethodsWe acquired HH-OCT images (n=278) from a prospective mixed cross-sectional longitudinal observational study of 87 participants (23-36 weeks gestational age (GA); n=30 with ROP, n=57 without ROP) between 31 to 44 weeks postmenstrual age (PMA) excluding treated ROP and features of cystoid macular edema (CME). Six retinal layer thicknesses from the fovea to the parafovea were analysed at five locations up to 1000 µm temporally and nasally.ResultsThe mean outer retinal thickness (OUTRETL) during active ROP increased at the fovea and parafovea from PMA 33 to 39 weeks ( p ConclusionsIncreased foveal and parafoveal outer retina measured using HH-OCT shows potential as a marker for ROP screening

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

CHIASM-Net: Artificial Intelligence-Based Direct Identification of Chiasmal Abnormalities in Albinism

Purpose: Albinism is a congenital disorder affecting pigmentation levels, structure, and function of the visual system. The identification of anatomical changes typical for people with albinism (PWA), such as optic chiasm malformations, could become an important component of diagnostics. Here, we tested an application of convolutional neural networks (CNNs) for this purpose. Methods: We established and evaluated a CNN, referred to as CHIASM-Net, for the detection of chiasmal malformations from anatomic magnetic resonance (MR) images of the brain. CHIASM-Net, composed of encoding and classification modules, was developed using MR images of controls (n = 1708) and PWA (n = 32). Evaluation involved 8-fold cross validation involving accuracy, precision, recall, and F1-score metrics and was performed on a subset of controls and PWA samples excluded from the training. In addition to quantitative metrics, we used Explainable AI (XAI) methods that granted insights into factors driving the predictions of CHIASM-Net. Results: The results for the scenario indicated an accuracy of 85 ± 14%, precision of 90 ± 14% and recall of 81 ± 18%. XAI methods revealed that the predictions of CHIASM-Net are driven by optic-chiasm white matter and by the optic tracts. Conclusions: CHIASM-Net was demonstrated to use relevant regions of the optic chiasm for albinism detection from magnetic resonance imaging (MRI) brain anatomies. This indicates the strong potential of CNN-based approaches for visual pathway analysis and ultimately diagnostics.</p

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