Corneal nerves and amyotrophic lateral sclerosis: an in vivo corneal confocal imaging study.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27 months. In vivo corneal confocal microscopy, assessing the sub-basal nerve plexus of the cornea, has been proposed as a potential biomarker for ALS. We aimed to determine whether the assessment of corneal nerves using in vivo confocal microscopy can serve as an imaging biomarker for ALS. METHODS: A single-centre prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. The corneal sub-basal nerve plexus was analysed using in vivo confocal microscopy. An automated algorithm (ACCMetrics) was used to evaluate corneal parameters: nerve fibre density, nerve branch density, nerve fibre length, nerve fibre area, nerve total branch density, nerve fibre width, and nerve fractal dimension. RESULTS: Twenty-two patients with ALS and 30 controls were included. No significant differences were found between ALS and control groups for all corneal parameters (p > 0.05). Corneal sensitivity did not differ between groups, and no correlation was identified between corneal nerve parameters and ALS disease duration, severity and rate of progression (p > 0.05). CONCLUSIONS: The present study does not support the use of in vivo corneal confocal microscopy as an early diagnostic or prognostic tool for ALS. Further research, especially longitudinal investigations, is needed to understand any potential corneal innervation changes as ALS progresses.

Validation of metabolomic and lipidomic analyses of human tears using ultra-high-performance liquid chromatography tandem mass spectrometry.

To facilitate application in ophthalmological and systemic diseases, there is a need to standardize preanalytical and analytical steps for metabo-lipidomics in human tears. We assessed different methods for each step of the workflow, from sampling to omics profiles acquisition, to provide the largest metabo-lipidomic coverage with the most robust analytical criteria in human tears. We compared reproducibility according to different extraction methods, two sampling techniques, three volumes (2 µL, 5 µL, 10 µL) and eye laterality using ultra-high-performance liquid chromatography coupled with tandem high-resolution mass spectrometry for metabolomic and lipidomic application. The effect of age on the tear metabo-lipidome was also investigated in healthy subjects. The extraction method using methanol/water provided the best results for Schirmer strip metabolomics, while Folch extraction was superior for lipidomics, whatever the sampling method used. When comparing both sampling methods, microcapillary glass tube was superior to Schirmer strip for metabolomics but comparable for lipidomics. The 5 µL volume provided a satisfying metabo-lipidomic coverage. There was no significant difference in tear metabo-lipidome between both eyes in healthy subjects. While most metabolites and lipids where not influenced by age, the phenylalanine-tyrosine-tryptophan pathway, aminoacyl t-RNA biosynthesis, and alanine-aspartate-glutamate metabolism were the 3 principal pathways associated with the 15 most variable metabolites according to age. The current findings will contribute to improve metabo-lipidomic workflow in human tears for the identification of new biomarkers. Preanalytical and analytical standardization is mandatory in order to perform better between-study comparisons and increase the chances of transferring laboratory findings into clinical practice.

Refractive errors in a large dataset of French children: the ANJO study.

Undetected refractive errors (REs) in children can lead to irreversible vision loss. This study aimed to show the proportions of REs in French children using cycloplegic refraction. Multicentre cross-sectional retrospective study including children with cycloplegic refraction and without associated ocular conditions from 2015 to 2018 in French eye clinics. The following data were collected: age, symptoms of eye strain, best-corrected visual acuity (BCVA), cycloplegic refraction. The analysis included 48,163 children (mean age: 7.75 years, range: 2 to 12 years). The proportion of each RE was as follows: emmetropia (- 0.50 < Spherical Equivalent (SE) ≤ + 2.0; 58.3%), hyperopia (+ 2.0 [Formula: see text] SE [Formula: see text]+5; 17.2%), myopia (- 6 [Formula: see text] SE [Formula: see text]- 0.50; 15.5%), high myopia (SE < - 6; 0.5%), high hyperopia (SE > + 5; 3.6%), mixed astigmatism (4.9%). Anisometropia (SE difference ≥ 1.5) was found in 5.0%. Functional amblyopia in children attending primary school (aged over 6 years) was encountered in 2.7%. Symptoms of eye strain were frequent (70%) but not specific to any RE. REs are frequently found in French children and may remain undetected in the absence of symptoms of eye strain. Few studies have investigated REs in children using cycloplegic refraction, which has been shown to be the gold standard for RE assessment.

Metabolomics and lipidomics approaches in human tears: A systematic review.

The human tear film is at the interface between the ocular surface and the external environment. Although investigation has been hindered by its small volume, improvements in preanalytical and analytical methods have allowed the omics approach to represent an innovative biomarker search strategy. There is still a significant lack of standardization, representing a barrier for performing between-studies comparisons and transferring experimental findings into clinical use and trials. We summarize the preanalytical and analytical procedures, describe the biomarkers that can be found using the metabo-lipidomics approach, and provide our expert opinion for omics investigations in human tears. For this systematic review of 38 studies, we searched PubMed by combining Boolean operators with the following keywords: tear, metabolomic, lipidomic, -omics. The human tear metabo-lipidome has been well-characterized in normal individuals using high-resolution liquid chromatography coupled with mass spectrometry. Lipid and metabolite profiles were influenced by ocular (e.g., dry eye disorders; Meibomian gland dysfunction; contact lens wear; glaucoma; keratoconus; pterygium) and systemic conditions (e.g., multiple sclerosis). Investigating the tear metabo-lipidome could improve our understanding of the pathogenesis of both ocular and systemic diseases, but also provide diagnostic as well as prognostic biomarkers.

Strabismus outcomes after surgery: the nationwide SOS France study.

PURPOSE: To describe the types of strabismus operated on, the surgical procedures performed, and the 2-year reoperation rate in France. METHODS: Entire population 5-year cross-sectional analysis of a national medico-administrative database in France between January 2013 and December 2017 included all patients who underwent a first strabismus surgery, with a 2-year follow-up. Patient identification was based on the diagnostic codes of the 10th International Classification of Diseases and surgical procedures on the codes of the Common Classification of Medical Acts. A subgroup analysis comparing non-paralytic and paralytic strabismus was performed. RESULTS: Among the 56,654 patients included (women: 50.8%), 26,892 (47.5%) patients were under 10 years old. Overall, 52,711 (93%) were diagnosed with non-paralytic strabismus and 3,943 (7%) with paralytic strabismus. Among the non-paralytics, the most frequent diagnosis was esotropia (21,282, 37.6%), followed by exotropia (14,392, 25.4%) and vertical strabismus (2,017, 3.6%). Among the paralytics, fourth cranial nerve palsy (1,499, 2.6%) was more frequent than sixth cranial nerve palsy (691, 1.2%) and third cranial nerve palsy (431, 0.8%). The 2-year reoperation rate was 7.7% (4,362 patients), the lowest for non-paralytic (7.4%) and the highest for paralytic (11.4%). CONCLUSION: This first French population-based study about strabismus will contribute to the evaluation of practices at a national level and permit comparisons between countries. Although the 2-year reoperation rate was found to be 1 out of 13 patients, it should be interpreted with caution. Long-term follow-up is still warranted due to considerable variability of the type and severity of strabismus as well as surgical practices.

Reduced visual evoked potential amplitude in autism spectrum disorder, a variability effect?

Atypical sensory behaviours represent a core symptom of autism spectrum disorder (ASD). Investigating early visual processing is crucial to deepen our understanding of higher-level processes. Visual evoked potentials (VEPs) to pattern-reversal checkerboards were recorded in ASD children and age-matched controls. Peak analysis of the P100 component and two types of single-trial analyses were carried out. P100 amplitude was reduced in the ASD group, consistent with previous reports. The analysis of the proportion of trials with a positive activity in the latency range of the P100, measuring inter-trial (in)consistency, allowed identifying two subgroups of ASD participants: the first group, as control children, showed a high inter-trial consistency, whereas the other group showed an inter-trial inconsistency. Analysis of median absolute deviation of single-trial P100 (st-P100) latencies revealed an increased latency variability in the ASD group. Both single-trial analyses revealed increased variability in a subset of children with ASD. To control for this variability, VEPs were reconstructed by including only positive trials or trials with homogeneous st-P100 latencies. These control analyses abolished group differences, confirming that the reduced P100 amplitude results from increased inter-trial variability in ASD. This increased variability in ASD supports the neural noise theory. The existence of subgroups in ASD suggests that the neural response variability is not a genuine characteristic of the entire autistic spectrum, but rather characterized subgroups of children. Exploring the relationship between sensory responsiveness and inter-trial variability could provide more precise bioclinical profiles in children with ASD, and complete the functional diagnostic crucial for the development of individualized therapeutical projects.

Objective ocular surface tolerance in patients with glaucoma treated with topical preserved or unpreserved prostaglandin analogues.

PURPOSE: Preservatives in glaucoma medications have been associated with ocular toxicity. We compared ocular signs and symptoms in patients with open-angle glaucoma or ocular hypertension treated in monotherapy with preserved or preservative-free prostaglandin analogues. METHODS: Observational cross-sectional clinical study in real life. 82 patients treated for at least 6 months with prostaglandin analogue were assessed for intraocular pressure, ocular symptoms and ocular signs including conjunctival hyperaemia, tear break-up time and tear meniscus height measured using objective and non-invasive methods (OCULUS Keratograph 5M). Patients presenting with symptoms of ocular toxicity with preserved prostaglandin analogues were switched to preservative-free latanoprost, and a second assessment was processed 6 months after. RESULTS: At inclusion, 30 (36.6%) patients were treated with preservative-free latanoprost, 25 (30.5%) with preserved latanoprost, 16 (19.5%) with preserved travoprost and 11 (13.4%) with preserved bimatoprost. Patients treated with preservative-free latanoprost reported significantly less ocular symptoms upon instillation (mainly burning) and between instillations than patients treated with preserved prostaglandin analogues. The mean conjunctival hyperaemia (limbal + bulbar) was significantly lower with preservative-free latanoprost (2.08 ± 0.55) compared to preserved latanoprost (2.50 ± 0.7, p = 0.0085), preserved travoprost (2.67 ± 0.82, p = 0.0083) and preserved bimatoprost (2.68 ± 0.67, p = 0.0041). There were no relevant between-group differences in mean tear meniscus height and break-up time. Ocular symptoms and conjunctival hyperaemia improved when preserved prostaglandin analogues were switched to preservative-free latanoprost for 6 months while intraocular pressure reduction was maintained. CONCLUSION: Overall, this study suggests a better subjective and objective ocular tolerance when patients were treated with preservative-free latanoprost than with other preserved prostaglandin analogues monotherapy. Switching to preservative-free latanoprost maintained intraocular pressure at the same level as preservative prostaglandin analogue, but improved ocular surface tolerance.