Learning the Optimal Control of Coordinated Eye and Head Movements

Various optimality principles have been proposed to explain the characteristics of coordinated eye and head movements during visual orienting behavior. At the same time, researchers have suggested several neural models to underly the generation of saccades, but these do not include online learning as a mechanism of optimization. Here, we suggest an open-loop neural controller with a local adaptation mechanism that minimizes a proposed cost function. Simulations show that the characteristics of coordinated eye and head movements generated by this model match the experimental data in many aspects, including the relationship between amplitude, duration and peak velocity in head-restrained and the relative contribution of eye and head to the total gaze shift in head-free conditions. Our model is a first step towards bringing together an optimality principle and an incremental local learning mechanism into a unified control scheme for coordinated eye and head movements

Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial

Background: Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. Methods: EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3–8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. Findings: Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. Interpretation: The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. Funding: Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation

Severity of cystoid macular oedema in preterm infants observed using hand-held spectral domain optical coherence tomography improves weekly with postmenstrual age

Objective: To investigate the relationship between cystoid macular oedema (CMO) measured in preterm infants using hand-held spectral domain optical coherence tomography (HH SD-OCT), with gestational age at birth (GA), birthweight (BW), diagnosis of retinopathy of prematurity (ROP) and the presence or absence of the external limiting membrane (ELM). Methods: We conducted a prospective mixed cross-sectional/longitudinal observational study of 112 participants (23 to 36 weeks GA; n = 25 with, and n = 87 without, CMO). Retinal images were acquired using 344 HH SD-OCT (n = 66 with and n = 278 without, CMO) between 31 to 44 weeks postmenstrual age (PMA). CMO type (‘fovea’ and ‘dome’) was measured using thickness, width, area and peak. Results: CMO was observed in 22.9% of preterm infants, and 19.2% of images. The mean values for thickness, width, area and peak of ‘dome’ CMO were 128.47 µm (SD +/- 34.23), 3624.45 µm (SD +/- 1323.03), 0.49 mm2 (SD +/- 0.28) and 279.81 µm (SD +/- 13.57) respectively. The mean values for thickness, width, area and peak of ‘fovea’ CMO were 64.37 µm (SD +/- 17.11), 2226.28 µm (SD +/- 1123.82), 0.16 mm2 (SD +/- 0.11) and 95.03 µm (SD +/- 26.99) respectively. Thickness, area width and peak were significantly greater for ‘dome CMO compared with ‘fovea’ CMO (P < 0.0001 for thickness, area and peak; P < 0.01 for width). Area and width significantly decreased with PMA for ‘dome’ and ‘fovea’ CMO (p = 0.0028; p < 0.001 respectively). No association was found between the presence of ROP and the detection of CMO or detection of CMO with absence of ELM. Conclusions: HH -OCT in preterm infants demonstrates that the severity of CMO appearance improves each week for both fovea and dome CMO

Short-term progression of optic disc and macular changes in optic nerve head drusen

Purpose: To quantify in patients with optic nerve head drusen (ONHD)changes after 1-year observation in: (i) optic disc and (ii) macular optical coherence tomography (OCT) parameters and (iii) the effect of age at enrolment in the study. Design: Prospective, cross-sectional observational study using Spectral Domain-OCT (Copernicus; OPTOPOL Technology S.A., Zawiercie, Poland) imaging was carried out in 35 patients with ONHD (age–42.8 ± 19.9 years; males = 15; females = 20) at baseline and after 12 months follow-up. Results: Patients with ONHD had significant thinning of the surface nerve fibre layer in the central (p = 0.03), superior (p = 0.05) and inferior (p = 0.04) areas; mean ppRNFL thinning (p = 0.0 4) and ppRNFL thinning in the nasal segment (p = 0.028). Retinal thinning in the central (p = 0.001), inner (p = 0.01) and outer (p = 0.002) temporal, outer superior (p = 0.03) and inferior (p = 0.02) areas; borderline ganglion cell layer thinning (p = 0.051) and outer nuclear layer (p = 0.03) thinning in the central retina and outer segment layer thinning nasally (p = 0.01) between the first and the second visit in macula. Correlation of the difference in optic disc and macular parameters with the age at enrolment did not reveal any significance. Conclusions: Statistically detectable thinning of the optic nerve and macula structures occurred already after 12 months. The proximity of optic nerve changes to the vascular arcades can possibly be explained by involvement of retinal vessels in the pathophysiology of ONHD

Detection and characterisation of optic nerve and retinal changes in primary congenital glaucoma using hand-held optical coherence tomography

Objective To investigate (1) the feasibility of scanning the optic nerve (ON) and central retina with hand-held optical coherence tomography (HH-OCT) without sedation or anaesthesia in primary congenital glaucoma (PCG), (2) the characteristics of ON changes in comparison with adult primary open-angle glaucoma (POAG) in comparison with matched controls, (3) the sensitivity and specificity of ON parameters for diagnosis, and (4) changes of foveal morphology. Methods and analysis HH-OCT (Envisu 2300; Leica Microsystems) was used to investigate ON and foveal morphology of 20 children with PCG (mean age 4.64±2.79) and 10 adult patients with POAG (mean age 66.8±6.94), and compared with age-matched, gender-matched and ethnicity-matched healthy controls without sedation or anaesthesia. Results HH-OCT yielded useful data in 20 out of 24 young children with PCG. Patients with PCG had significantly deeper cup changes than patients with POAG (vs respective age-matched controls, p=0.014). ON changes in PCG are characterised by significant increase in cup depth (165%), increased cup diameter (159%) and reduction in rim area (36.4%) as compared with controls with high sensitivity (81.5, 74.1% and 88.9%, respectively) and specificity (85.0, 80.0% and 75.0%, respectively). Patients with PCG have a significantly smaller width of the macula pit (p<0.001) with non-detectable external limiting membrane. Conclusion HH-OCT has the potential to be a useful tool in glaucoma management for young children. We have demonstrated the use of HH-OCT in confirming a diagnosis of glaucoma within the studied cohort and found changes in disc morphology which characterise differently in PCG from POAG

Diagnostic accuracy of retinal optical coherence tomography in children with a newly diagnosed brain tumour

Purpose: To estimate the diagnostic accuracy of circumpapillary retinal nerve fibre layer (RNFL) thickness and macular ganglion cell layer–inner plexiform layer (GCL-IPL) thickness measurements to discriminate an abnormal visual function (i.e. abnormal age-based visual acuity and/or visual field defect) in children with a newly diagnosed brain tumour. Methods: This cross-sectional analysis of a prospective longitudinal nationwide cohort study was conducted at four hospitals in the Netherlands, including the national referral centre for paediatric oncology. Patients aged 0–18 years with a newly diagnosed brain tumour and reliable visual acuity and/or visual field examination and optical coherence tomography were included. Diagnostic accuracy was evaluated with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: Of 115 patients included in the study (67 [58.3%] male; median age 10.6 years [range, 0.2–17.8 years]), reliable RNFL thickness and GCL-IPL thickness measurements were available in 92 patients (80.0%) and 84 patients (73.0%), respectively. The sensitivity for detecting an abnormal visual function was 74.5% for average RNFL thickness and 41.7% for average GCL-IPL thickness at a specificity of 44.5% and 82.9%, respectively. The PPV and NPV were 33.0% and 82.6% for the average RNFL thickness and 57.1% and 82.2% for the average GCL-IPL thickness. Conclusion: An abnormal visual function was discriminated correctly by using the average RNFL thickness in seven out of ten patients and by using the average GCL-IPL thickness in four out of ten patients. The relatively high NPVs signified that patients with normal average RNFL thickness and average GCL-IPL thickness measurements had a relative high certainty of a normal visual function

Discordant phenotypes in twins with infantile nystagmus

Infantile nystagmus (IN) may result from aetiologies including albinism and FRMD7 mutations. IN has low prevalence, and twins with IN are rare. Whilst discordant presentation has been previously reported for IN, we present for the first time the comprehensive assessment of diagnostically discordant monozygotic twins. From a cohort of over 2000 patients, we identified twins and triplets discordant for nystagmus. Using next-generation sequencing, high-resolution infra-red pupil tracking and optical coherence tomography, we characterised differences in genotype and phenotype. Monozygotic twins (n = 1), dizygotic twins (n = 3) and triplets (n = 1) were included. The monozygotic twins had concordant TYR variants. No causative variants were identified in the triplets. Dizygotic twins had discordant variants in TYR, OCA2 and FRMD7. One unaffected co-twin demonstrated sub-clinical nystagmus. Foveal hypoplasia (FH) was noted in four of five probands. Both co-twins of the monozygotic pair and triplets displayed FH. In three families, at least one parent had FH without nystagmus. FH alone may be insufficient to develop nystagmus. Whilst arrested optokinetic reflex pathway development is implicated in IN, discordant twins raise questions regarding where differences in development have arisen. In unaffected monozygotes therefore, genetic variants may predispose to oculomotor instability, with variable expressivity possibly responsible for the discordance observed