Potential Utility of Foveal Morphology in Preterm Infants Measured using Hand-Held Optical Coherence Tomography in Retinopathy of Prematurity Screening

Financial Support: Medical Research Council, London, UK (grant number: MR/N004566/1 and MR/J004189/1), Ulverscroft Foundation, Leicester, UK, Nystagmus Network UK. Acknowledgements: The authors acknowledge the assistance of Deputy Sister Hima Thanki in assisting with the acquisition of HH-OCT images and the Staff of the University Hospitals of Leicester Neonatal Service in supporting the infants during the imaging sessions.Peer reviewedPublisher PD

Electrophysiological and fundoscopic detection of intracranial hypertension in craniosynostosis

Aims: To assess the diagnostic accuracy of fundoscopy and visual evoked potentials (VEPs) in detecting intracranial hypertension (IH) in patients with craniosynostosis undergoing spring-assisted posterior vault expansion (sPVE). Methods: Children with craniosynostosis undergoing sPVE and 48-hour intracranial pressure (ICP) monitoring were included in this single-centre, retrospective, diagnostic accuracy study. Data for ICP, fundoscopy and VEPs were analysed. Primary outcome measures were papilloedema on fundoscopy, VEP assessments and IH, defined as mean ICP &gt; 20 mmHg. Diagnostic indices were calculated for fundoscopy and VEPs against IH. Secondary outcome measures included final visual outcomes. Results: Fundoscopic examinations were available for 35 children and isolated VEPs for 30 children, 22 of whom had at least three serial VEPs. Sensitivity was 32.1% for fundoscopy (95% confidence intervals [CI]: 15.9–52.4) and 58.3% for isolated VEPs (95% CI 36.6–77.9). Specificity for IH was 100% for fundoscopy (95% CI: 59.0–100) and 83.3% for isolated VEPs (95% CI: 35.9–99.6). Where longitudinal deterioration was suspected from some prVEPs but not corroborated by all, sensitivity increased to 70.6% (95% CI: 44.0–89.7), while specificity decreased to 60% (95% CI: 14.7–94.7). Where longitudinal deterioration was clinically significant, sensitivity decreased to 47.1% (23.0–72.2) and specificity increased to 100% (47.8–100). Median final BCVA was 0.24 logMAR (n = 36). UK driving standard BCVA was achieved by 26 patients (72.2%), defined as ≥0.30 logMAR in the better eye. Conclusion: Papilloedema present on fundoscopy reliably indicated IH, but its absence did not exclude IH. VEP testing boosted sensitivity at the expense of specificity, depending on method of analysis.</p

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

Cerebral malaria: insight into pathology from optical coherence tomography

AbstractWe aimed to investigate structural retinal changes in malarial retinopathy (MR) using hand-held optical coherence tomography (HH-OCT) to assess its diagnostic potential. Children with MR (n = 43) underwent ophthalmoscopy, fluorescein angiography and HH-OCT during admission, 1-month (n = 31) and 1-year (n = 8) post-discharge. Controls were comatose patients without malaria (n = 6) and age/sex-matched healthy children (n = 43). OCT changes and retinal layer thicknesses were compared. On HH-OCT, hyper-reflective areas (HRAs) were seen in the inner retina of 81% of MR patients, corresponding to ischaemic retinal whitening on fundus photography. Cotton wool spots were present in 37% and abnormal hyper-reflective dots, co-localized to capillary plexus, in 93%. Hyper-reflective vessel walls were present in 84%, and intra-retinal cysts in 9%. Vascular changes and cysts resolved within 48 h. HRAs developed into retinal thinning at 1 month (p = 0.027) which was more pronounced after 1 year (p = 0.009). Ischaemic retinal whitening is located within inner retinal layers, distinguishing it from cotton wool spots. Vascular hyper-reflectivity may represent the sequestration of parasitized erythrocytes in vessels, a key CM feature. The mechanisms of post-ischemic retinal atrophy and cerebral atrophy with cognitive impairment may be similar in CM survivors. HH-OCT has the potential for monitoring patients, treatment response and predicting neurological deficits.</jats:p

Management of nystagmus in children : a review of the literature and current practice in UK specialist services

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management

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

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

Ophthalmology

To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). Multicenter, observational study. A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 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 OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. Grade of FH, presence or absence of photoreceptor specialization (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 achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism 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 with other diagnoses associated with FH. We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value

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

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.Peer reviewedPublisher PD

Vertical optokinetic nystagmus in adults with or without Parkinson's Disease

Background: Horizontal OKN is widely investigated and it is accepted that there is no horizontal OKN asymmetry in healthy adults. Vertical OKN is less well investigated and the direction of vertical OKN asymmetry is unclear. Aims: To investigate vertical OKN asymmetry in healthy individuals under of variety of different experimental conditions comparing: (i) the performance of look versus stare OKN, the effects of (ii) stimulus velocity, (iii) luminance profile, (iv) stimulus size and shape, and (v) distance on vertical OKN responses. The effect of neurological disease on OKN asymmetry in the form of Parkinson's disease was also investigated. Methods: OKN responses were recorded in healthy adult volunteers under a variety of experimental conditions including: (i) working distances of 33cm, lm, 1.2m and 2.5m (ii) sinusoidal and square wave OKN targets (iii) different target sizes ranging in size from 22.4°x28.9° to 65°x 55° (iv) contrasts of 50% to 100% and (v) target velocities of 20°/s and 40°/s investigating 'look and 'stare' OKN response. Stare OKN responses were also compared in subjects with Parkinson's disease and age-matched controls. All data was recorded using an infrared video pupil tracker. Result: No clear vertical OKN asymmetry was seen in normal adult subjects although the degree and direction of vertical OKN asymmetry remained relatively consistent for an individual under different stimulus conditions. Of all stimulus parameters target size had the greatest effect on vertical OKN asymmetry. Stare OKN was sensitive to distance for stimuli moving in the downwards direction. Parkinson's disease patients also had greatly reduced OKN responses for stimuli moving in the downward direction. Discussion: We found sensitivity of 'stare' OKN responses during downward stimulation to both target distance and the effects of Parkinson's disease. It is possible that this is related to the function of OKN during navigation, which is under cerebellar control.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The effect of font size on reading performance in strabismic amblyopia: an eye movement investigation.

PURPOSE: We investigated the effect of font size on reading speed and ocular motor performance in strabismic amblyopes during text reading under monocular and binocular viewing conditions. METHODS: Eye movements were recorded at 250 Hz using a head-mounted infrared video eye tracker in 15 strabismic amblyopes and 18 age-matched controls while silently reading paragraphs of text at font sizes equivalent to 1.0 to 0.2 logMAR acuity. Reading under monocular viewing with amblyopic eye/nondominant eye and nonamblyopic/dominant eye was compared to binocular viewing. Mean reading speed; number, amplitude, and direction of saccades; and fixation duration were calculated for each font size and viewing condition. RESULTS: Reading speed was significantly slower in amblyopes compared to controls for all font sizes during monocular reading with the amblyopic eye (P = 0.004), but only for smaller font sizes for reading with the nonamblyopic eye (P = 0.045) and binocularly (P = 0.038). The most significant ocular motor change was that strabismic amblyopes made more saccades per line than controls irrespective of font size and viewing conditions (P < 0.05 for all). There was no significant difference in saccadic amplitudes and fixation duration was only significantly longer in strabismic amblyopes when reading smaller fonts with the amblyopic eye viewing. CONCLUSIONS: Ocular motor deficits exist in strabismic amblyopes during reading even when reading speeds are normal and when visual acuity is not a limiting factor; that is, when reading larger font sizes with nonamblyopic eye viewing and binocular viewing. This suggests that these abnormalities are not related to crowding