Exploring amyotrophic lateral sclerosis through the visual system: A systematic review.

BACKGROUND AND PURPOSE: The human visual system relies on neural networks throughout the brain that are easily accessible for tests exploring eye structures and movements. Over the past two decades, investigations have been carried out on both afferent and efferent components of the visual system in people with amyotrophic lateral sclerosis (ALS). This approach might represent an innovative biomarker research strategy to better characterise the phenotypic variability of ALS. The purpose of this review was to determine whether exploring the visual system of patients with ALS (pwALS) is an effective strategy. METHODS: The Medline and Web of science databases were searched for studies with terms relating to ALS and vision. Of 1146 references identified, 43 articles were included. RESULTS: In this review article, both afferent and efferent components of the visual system were found to be impaired in pwALS in the absence of visual complaint, thereby contributing to the hypothesis that ALS is a multisystem disease with sensory involvement. Of note, some areas of the eye remain unexplored (i.e., tears, and retinal function using electroretinography). CONCLUSIONS: According to the findings available in the literature, investigating the oculomotor system and exploring the ocular surface could represent two key promising strategies to identify new diagnostic biomarkers in pwALS. Further longitudinal studies are needed to identify relevant indicators of disease progression and response to therapeutic intervention.

Learning curves of novice residents on cataract surgery simulator: the E3CAPS pedagogic study.

INTRODUCTION: Training novice ophthalmology residents on the EyeSi® simulator increases cataract surgery safety. However, there is no consensus regarding how much training residents should perform before their first time on patients. We evaluated the French national training program through the analysis of the learning curves of novice residents. METHODS: This prospective multicentric pedagogic study was conducted with French novice residents. Each resident completed the recommended four two-hour training sessions and performed a standardized assessment simulating standard cataract surgery before the first session (A0), at the end of the first (A1), second (A2), third (A3) and fourth (A4) sessions. For each surgical step of each attempt, the following data were collected: score, odometer, completion time, posterior capsular rupture and cumulative energy delivered (ultrasounds) during phacoemulsification. A performance threshold was set at a score of 80/100 for each surgical step, 400/500 for the overall procedure. Only descriptive statistics were employed. RESULTS: Sixteen newly nominated ophthalmology residents were included. Median score progressively increased from 95 [IQR 53; 147]) at A0 to 425 [IQR 411; 451] at A4. Despite a significant progression, the "emulsification" step had the lowest A4 scores 86 [IQR 60; 94] without reduction in completion time, odometer or ultrasounds delivered. The rate of posterior capsular rupture decreased linearly from 75% at A0 to 13% at A4 during "emulsification" and from 69 to 0% during "irrigation and aspiration". At A4, only 25% [8; 53] of residents had > 80 at each step and only 75% [47; 92] had > 400/500 overall. CONCLUSION: A training program consisting of four two-hour sessions on the EyeSi simulator over four consecutive days effectively enhances the surgical skills of novice ophthalmology residents. Undergoing more training sessions may improve scores and decrease the incidence of surgical complications, particularly at the emulsification step of cataract surgery. The learning curves presented here can reassure residents who are progressing normally and help identify those who need a further personalized training program.  TRIAL REGISTRATION: ClinicalTrials registration number: NCT05722080 (first submitted 22/12/2022, first posted 10/02/2023).

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.

A Rare Case of Didanosine-Induced Mid-Peripheral Chorioretinal Atrophy Identified Incidentally 11 Years after the Drug Cessation.

Objective: This article aims to describe a unique case of didanosine-induced retinal degeneration that was discovered 11 years after the drug withdrawal. Case report: The patient is a 42-year-old woman with a medical history of HIV and hepatitis C virus since 2004. She has been prescribed antiretroviral therapy since then. For the first seven years (2004-2011), the patient was prescribed a combination therapy consisting of didanosine, efavirenz, and lamivudine. The protocol was changed to atripla (efavirenz, emtricitabine, and tenofovir) from 2011 to 2021. Recently (October 2021-January 2021), the patient was prescribed eviplera (rilpivirin, emtricitabine, and tenofovir). In addition, her past medical history revealed Gougerot-Sjogren syndrome and rheumatoid arthritis. She was prescribed hydroxychloroquine (HCQ) (2009-2021) at a dose of 400 mg daily. She had no vision complaint. Results: During her routine HCQ screening at the eye clinic, University Hospital Bretonneau, Tours, France, the widefield colour fundus photograph showed well-defined symmetric mid-peripheral areas of chorioretinal atrophy sparing the posterior pole of both eyes. Furthermore, the widefield fundus autofluorescence illustrated mid-peripheral round well-demarcation hypoautofluorescent areas of chorioretinal atrophy of both eyes. Conversely, the macular optical coherence tomography (OCT) was normal. Many of her drugs are known to be associated with retinopathy such as HCQ, tenofovir, efavirenz, and didanosine. Because our data corroborate peripheral retinal damage rather than posterior pole damage, this case report is compatible with didanosine-induced retinopathy rather than HCQ, efavirenz, or tenofovir retinal toxicity. Conclusions: All HIV patients who are presently or were previously on didanosine therapy should have their fundus examined utilising widefield fundus autofluorescence and photography.

Femtosecond laser-assisted versus phacoemulsification cataract surgery (FEMCAT): a multicentre participant-masked randomised superiority and cost-effectiveness trial.

BACKGROUND: Cataract surgery is one of the most common operations in health care. Femtosecond laser-assisted cataract surgery (FLACS) enables more precise ocular incisions and lens fragmentation than does phacoemulsification cataract surgery (PCS). We hypothesised that FLACS might improve outcomes in cataract surgery compared with PCS despite having higher costs. METHODS: We did a participant-masked randomised superiority clinical trial comparing FLACS and PCS in two parallel groups (permuted block randomisation stratified on centres via a centralised web-based application, allocation ratio 1:1, block size of 2 or 4 for unilateral cases and 2 or 6 for bilateral cases). Five French University Hospitals enrolled consecutive patients aged 22 years or older who were eligible for unilateral or bilateral cataract surgery. Participants, outcome assessors, and technicians carrying out examinations were masked to the surgical treatment allocation until the last follow-up visit and a sham laser procedure was set up for participants randomly assigned to the PCS arm. The primary clinical endpoint was the success rate of surgery, defined as a composite of four outcomes at a 3-month postoperative visit: absence of severe perioperative complication, a best-corrected visual acuity (BCVA) of 0·0 LogMAR (logarithm of the minimum angle of resolution) or better, an absolute refractive error of 0·75 dioptres or less, and unchanged postoperative corneal astigmatism power (≤0·5 dioptres) and axis (≤20°). The primary economic endpoint was the incremental cost per additional patient who had treatment success at 3 months. Primary outcomes were assessed in all randomly assigned patients who met all eligibility criteria (missing data considered as failure). We used mixed logistic regression models or mixed linear regression models for statistical comparisons, adjusted on centres and whether cataract surgery was bilateral or unilateral. The study is registered with ClinicalTrials.gov, NCT01982006. FINDINGS: Of the 907 patients (1476 eyes) randomly assigned between Oct 9, 2013, and Oct 30, 2015, 870 (704 eyes in FLACS group and 685 eyes in the PCS group) were analysed. We identified no significant difference in the success rate of surgery between the FLACS and PCS groups (FLACS: 41·1% [289 eyes]; PCS: 43·6% [299 eyes]); adjusted odds ratio 0·85, 95% CI 0·64-1·12, p=0·250). The incremental cost-effectiveness ratio was €10 703 saved per additional patient who had treatment success with PCS compared with FLACS. We observed no severe adverse events during the femtosecond laser procedure, and most of the complications in the FLACS group related to the primary outcome measures occurred during the phacoemulsification phase or postoperatively. INTERPRETATION: Despite its advanced technology, femtosecond laser was not superior to phacoemulsification in cataract surgery and, with higher costs, did not provide an additional benefit over phacoemulsification for patients or health-care systems. FUNDING: French Ministry of Social Affairs and Health.

Monocular and binocular visual parameters associated to vision-related quality of life in patients with epiretinal membrane: a prospective cohort.

PURPOSE: Binocular visual impairment related to unilateral idiopathic epiretinal membranes (uiERM) and its association with vision-related quality of life (VR-QoL) has not yet been investigated. This study aimed to explore binocular visual parameters (distance binocular best-corrected visual acuity (BCVA), aniseikonia, stereopsis) and VR-QoL in patients with uiERM. METHODS: We carried out a prospective single-centre cohort study. The following data were collected: VR-QoL (NEI VFQ-25), distance monocular and binocular BCVA, horizontal and vertical metamorphopsia (M-charts test), horizontal and vertical aniseikonia (NAT TEST) and stereoacuity (TNO test). Multiple linear regression analyses were performed to evaluate factors influencing VR-QoL. RESULTS: Forty-six patients with uiERM and visual complaints were included. Aniseikonia was found in 40 (80%) participants. Stereoacuity was poor (above 120 s of arc) in 46 (100%) participants. Distance monocular BCVA, horizontal metamorphopsia and horizontal aniseikonia were the factors associated with VR-QoL in patients with uiERM. CONCLUSIONS: In subjects presenting uiERM, aniseikonia is frequently found and stereopsis is constantly impaired. We advocate quantitative testing of metamorphopsia and aniseikonia in addition to BCVA for the assessment of global visual function. Further investigations are needed to evaluate the effect of vitrectomy on these parameters and VR-QoL. TRIAL REGISTRATION: EudraCT Number/ID RCB: 2016-A00252-49.

Ophthalmological findings in children with autism spectrum disorder.

PURPOSE: Eye pathology could be related to atypical visual behaviours and impaired social communication through visual cues in children with autism spectrum disorder (ASD). The main purpose of this prospective study was to assess ophthalmological disorders in children with ASD and to investigate the relationships with intellectual disability (ID) and ASD severity. METHODS: In this prospective study, comprehensive ophthalmological and oculomotor examinations were performed. ASD severity and verbal and performance intelligence quotients were determined using adapted scales. These clinical data were compared between groups of children based on the presence or absence of ophthalmological disorders and the achievement or not of visual acuity (VA) testing by using non-parametric statistical tests. RESULTS: Amongst a sample of 51 children, ophthalmological disorders were found in 39% of cases, with 35% having significant refractive errors and 10% presenting with strabismus. Children with ASD and ophthalmological disorders had significantly lower verbal (29.8 ± 14.7 compared with 44.3 ± 21.5; p = 0.010) and performance quotients (57.8 ± 18.3 compared with 67.59 ± 20; p = 0.049) but no significant result was found between the presence of ophthalmological disorders and ASD severity, level of communication and social contact, or modulating behaviour when changes occur. Children who did not achieve monocular VA testing (39%) had significantly lower verbal (25.1 ± 9.7 compared with 46.1 ± 20.9; p < 0.001) and performance quotients (52.7 ± 17 compared with 69.8 ± 18.8; p = 0.001), also presented higher social interaction impairment (p = 0.002), and expressed more important behavioural signs (p = 0.007). CONCLUSIONS: Ophthalmological disorders are frequently found in children with ASD, especially in those with ID. Ophthalmologists and child psychiatrists should pay attention to perform ophthalmological examination in children with ASD since eye disorders might remain undetected. A comprehensive examination by a paediatric ophthalmologist would help to improve the individual clinical description and the global intervention. TRIAL REGISTRATION: Clinical trial registration number: NCT02444117.

Objective ocular torsion outcomes after unilateral horizontal rectus surgery in infantile esotropia.

PURPOSE: To analyse objective ocular torsion among patients with infantile esotropia and to determine the effects of unilateral horizontal rectus surgery. METHODS: Sixty-eight patients (136 eyes) (range 4 to 16 years) who underwent unilateral horizontal rectus surgery for infantile esotropia participated in this retrospective single-centre study. Objective ocular torsion using fundus photography was assessed before surgery and 1 year later. We defined three groups of patients based on preoperative qualitative objective ocular torsion: physiological extorsion and pathological extorsion and intorsion. For each group, the disc-foveal angle was measured and analysed both before and after surgery. We looked for possible correlations between amount of esodeviation and disc-foveal angle size. RESULTS: Preoperatively, 28 (41%) patients had + 6.73 (± 2.66) degrees of physiological extorsion. Thirty-one (46%) patients had + 12.94 (± 3.67) degrees of pathological extorsion. Nine (13%) patients had - 1.99 (± 2.52) degrees of intorsion. After surgery, the number of subjects with physiological extorsion increased to 45 (66%). The number of patients with pathological extorsion decreased to 17 (25%) and the mean disc-foveal angle was significantly reduced by 1.80°. Six (9%) patients presented intorsion and the mean disc-foveal angle was significantly reduced by 2.28°. For the pathological extorsion group, the size of the disc-foveal angle before surgery was positively correlated to its reduction after surgery. Disc-foveal angle variation and distance esodeviation variation after surgery were positively correlated. CONCLUSIONS: These results highlight that pathological objective ocular torsion can be frequently found in infantile esotropia and is decreased after unilateral recession-plication surgery.

Sleep and mood changes in advanced age after blue-blocking (yellow) intra ocular lens (IOLs) implantation during cataract surgical treatment: a randomized controlled trial.

OBJECTIVES: Both advanced age and depression are characterized by changes in sleep patterns. Light exposure is one of the main synchronizers of circadian cycles and influences sleep by inhibiting melatonin secretion, which is mostly sensitive to light of low wavelengths (blue). Blue-blocking (yellow) intraocular lenses (IOLs) have supplanted the usual UV-blocking (clear) IOLs during cataract surgery to prevent age-related macular degeneration, however, the impact of yellow IOLs on sleep and mood is unclear. The purpose of this study was to compare the effects of yellow and clear IOLs on sleep and mood in aged patients undergoing bilateral cataract surgery. METHODS: A randomized controlled superiority study was conducted within three ophthalmic surgical wards in France. A total of 204 subjects (mean age 76.2 ± 7.5 years) were randomized into yellow or clear IOLs groups. Patients completed a sleep diary, the pictorial sleepiness scale and the Beck Depression Inventory (BDI) one week before and eight weeks after the last surgical procedure. RESULTS: According to an Intent To Treat (ITT) analysis, no significant difference was found between yellow and clear IOLs groups regarding sleep time, sleep latency, total sleep duration, quality of sleep and BDI scores. The rate of patients whose BDI score increased at the cutoff score of ≥5 after surgery was significantly higher in the yellow IOL group (n = 11, 13.1%) compared with the clear IOL group (n = 4; 4.7%); p = 0.02. CONCLUSIONS: Using yellow IOLs for cataract surgery doesn't significantly impact sleep but may induce mood changes in aging.

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.

Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study.

PURPOSE: Amyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes. METHODS: A single-center 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. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed. RESULTS: Twenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p > 0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid). CONCLUSION: This study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.

Ciclosporin A Cationic Emulsion 0.1% for the Management of Dry Eye Disease: Facts That Matter for Eye-Care Providers.

Dry eye disease (DED) is a chronic inflammatory disease of the ocular surface requiring long-term therapy. Severe forms of DED generally do not respond to tear substitutes alone or combined, and often require treatment with topical anti-inflammatory agents to break the vicious circle of inflammation. This review summarises data from randomised controlled trials and real-world evidence on the efficacy and safety of ciclosporin A 0.1% cationic emulsion (Ikervis®) for the management of DED. Improvements in clinical signs and symptoms were reported from as early as 4 weeks after treatment initiation, although it can take a few months to reach the full benefits. Treatment periods of up to 12 months provide sustained benefit to patients. In the most responsive patients, treatment discontinuation is possible with no further substantial relapse over 12 months in over 65% of patients. Transient local ocular effects are the most commonly reported adverse events.

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.

NOVATIVE: A Phase II/III, Multicenter, Double-masked, Randomized Study of Cyclosporine A 0.05% and 0.1% Ophthalmic Cationic Emulsion Versus Vehicle in Patients with Vernal Keratoconjunctivitis.

PURPOSE: This study evaluates the efficacy and tolerability of cyclosporine A cationic emulsion (CsA-CE) in patients ≥4 years of age with moderate-to-severe vernal keratoconjunctivitis (VKC). METHODS: This Phase II/III, multicenter, double-masked, dose-ranging study had 2 treatment periods: a 4-week, randomized, vehicle-controlled period in which patients received 0.05% CsA-CE, 0.1% CsA-CE, or vehicle eye drops 4 times daily (period 1) and a 3-month period in which patients received 0.05% CsA-CE or 0.1% CsA-CE 2 or 4 times daily (period 2). The primary efficacy end point was rating of subjective symptoms at day 28 in period 1 per the BenEzra scale. FINDINGS: All groups showed improvement in subjective VKC symptoms at day 28, without a statistically significant difference between 0.05% or 0.1% CsA-CE vs vehicle. Both CsA-CE doses produced statistically significant improvements in corneal fluorescein staining scores vs vehicle at day 28; improvements were evident as early as week 1 and continued through month 1. Progressive reduction in subjective itching was evident after week 1 and continued through month 1. Treatment for an additional 3 months further improved subjective symptoms and objective signs of VKC in both CsA-CE groups. Improvement was most notable with 0.1% CsA-CE in patients with severe keratitis. The safety and tolerability profile is favorable. IMPLICATIONS: Although treatment with 0.05% and 0.1% CsA-CE showed clinical efficacy in alleviating keratitis and itching as early as week 1, with sustained benefit through 1 month, the primary efficacy end point was not met. These findings informed the design of the Phase III trial of 0.1% CsA-CE (Vernal Keratoconjunctivitis Study). CLINICALTRIALS: gov identifier: NCT00328653.

Cost Utility and Value of Information Analysis of Femtosecond Laser-Assisted Cataract Surgery.

Importance: The efficacy and safety of femtosecond laser-assisted cataract surgery is well documented. An important requirement for decision makers is the evaluation of the cost-effectiveness of femtosecond laser-assisted cataract surgery (FLACS) over a sufficiently long horizon. Evaluating the cost-effectiveness of this treatment was a preplanned secondary objective of the Economic Evaluation of Femtosecond Laser Assisted Cataract Surgery (FEMCAT) trial. Objective: To estimate the cost utility of FLACS compared with phacoemulsification cataract surgery (PCS) on a 12-month time horizon. Design, Setting, and Participants: This multicenter randomized clinical trial compared FLACS with PCS in parallel groups. All FLACS procedures were performed using the CATALYS precision system. Participants were recruited and treated in ambulatory surgery settings in 5 university-hospital centers in France. All consecutive patients eligible for a unilateral or bilateral cataract surgery 22 years or older with written informed consent were included. Data were collected from October 2013 to October 2018, and data were analyzed from January 2020 to June 2022. Interventions: FLACS or PCS. Main Outcomes and Measures: Utility was measured through the Health Utility Index questionnaire. Costs of cataract surgery were estimated by microcosting. All inpatient and outpatient costs were collected from the French National Health Data System. Results: Of 870 randomized patients, 543 (62.4%) were female, and the mean (SD) age at surgery was 72.3 (8.6) years. A total of 440 patients were randomized to receive FLACS and 430 to receive PCS; the rate of bilateral surgery was 63.3% (551 of 870). The mean (SD) costs of cataract surgery were €1124.0 (€162.2; US $1235) for FLACS and €565.5 (€61.4; US $621) for PCS. The total mean (SD) cost of care at 12 months was €7085 (€6700; US $7787) in participants treated with FLACS and €6502 (€7323; US $7146) in participants treated with PCS. FLACS yielded a mean (SD) of 0.788 (0.009) quality-adjusted life-years (QALYs), and PCS yielded 0.792 (0.009) QALYs. The difference in mean costs was €545.9 (95% CI, -434.1 to 1525.8; US $600), and the difference in QALYs was -0.004 (95% CI, -0.028 to 0.021). The incremental cost-effectiveness ratio (ICER) was -€136 476 (US $150 000) per QALY. The cost-effectiveness probability of FLACS compared with PCS was 15.7% for a cost-effectiveness threshold of €30 000 (US $32 973) per QALY. At this threshold, the expected value of perfect information was €246 139 079 (US $270 530 231). Conclusions and Relevance: The ICER of FLACS compared with PCS was not within the $50 000 to $100 000 per QALY range frequently cited as cost-effective. Additional research and development on FLACS is needed to improve its effectiveness and lower its price. Trial Registration: ClinicalTrials.gov Identifier: NCT01982006.

[Management of binocular diplopia in the department of ophthalmic emergencies at the Regional University Hospital of Tours]. / Prise en charge des diplopies binoculaires aux urgences ophtalmologiques du Centre hospitalier régional universitaire de Tours.

OBJECTIVES: To describe the etiologies of binocular diplopia for patients presenting to the ophthalmologic emergency department of the Regional University Center Hospital (CHRU) of Tours. METHODS: This is a retrospective study of the medical records of patients who presented with binocular diplopia in the ophthalmic emergency department of the CHRU of Tours between January 1st and December 31st, 2019. Binocular diplopia was classified as paralytic or non-paralytic according to the ocular motility examination. RESULTS: One hundred twelve patients were included. The median age was 61 years. Internal referral from other hospital services represented 44.6% of the patients. On ophthalmological examination, 73.2% had paralytic diplopia, 13.4% non-paralytic diplopia and 13.4% normal examination. Neuroimaging was performed in 88.3% of cases, with 75.7% of patients receiving it on the same day. Oculomotor nerve palsy was the most frequent cause of diplopia in 58.9%, the majority represented by abducens nerve palsy (60.6%). The most frequent etiology of binocular diplopia was ischemic, with microvascular damage in 26.8% of cases and stroke in 10.7% of cases. CONCLUSION: Among patients assessed in an ophthalmological emergency department setting, one in ten patients had stroke. It is essential to inform patients of the urgent nature of ophthalmological evaluation in the case of acute binocular diplopia. Urgent neurovascular management is also mandatory and should be based on the clinical description provided by the ophthalmologist. Neuroimaging should be performed as soon as possible, based on the ophthalmologic and neurological findings.

Educational Concerns About the Safety of Cataract Surgery During Residency: The E3CAPS Pedagogic Study.

INTRODUCTION: Cataract surgery is the most common surgical procedure performed in France. While the incidence of intraoperative complications affecting visual prognosis is extremely low, given the large number of patients operated on, the absolute number of patients affected by complications is quite high. Complication rates are significantly higher when ophthalmology residents (ORs) perform the surgery. Although lack of experience remains the main risk factor, sleep deprivation may adversely affect ORs' successful surgery rate. The value of the EyeSi® surgical simulator in initial training has been demonstrated to increase cataract surgery safety through the transfer of surgical skills from the simulator to the operating room. However, there is no consensus regarding how much training is needed before the first-time ORs are allowed to operate. There is also no scientific evidence that sleep deprivation is associated with a decrease in surgical performance. Establishing a validated protocol for cataract surgery training using the EyeSi surgical simulator (referred to further as the EyeSi) and identifying risk factors for intraoperative complications related to sleep deprivation will improve cataract surgery safety and lead to the reorganization of our healthcare systems. METHODS AND PLANNED OUTCOMES: This multi-centre educational cohort study will include two distinct axes which will both aim to reduce the risks of cataract surgery. Enrollment will include 16 first-year ORs for Axis 1 and 25 experienced residents for Axis 2, all from the University Hospitals of Nantes, Tours, Angers and Rennes. Axis 1 will focus on investigating the learning curve of first-year ORs using the EyeSi, following the training program recommended by the "College des Ophtalmologistes Universitaires de France" in order to set up a future "licence to operate." Axis 2 will evaluate the impact of sleep deprivation on the surgical performance of experienced ORs using the EyeSi. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05722080.

Calcium oxalate crystals retinopathy following domino liver transplant: A case report.

INTRODUCTION: Hyperoxaluria is a rare cause of hereditary crystalline retinopathy. We report the first case of acquired calcium oxalate crystalsretinopathy following domino liver transplantation (DLT). CLINICAL CASE: A 72-year-old patient was referred for bilateral visual impairment 9 months after DLT. Slit lamp examination was unremarkable. Fundus examination revealed calcium oxalate crystals accumulation within both retina. Owing to multi-organ failure, the patient underwent combined liver-kidney retransplantation. During the following two years, calcium oxalate crystals accumulation within the retina gradually decreased and visual acuity improved. Nevertheless, OCT-angiography revealed abnormalities in the inner and outer retinal vascular plexus (i.e. retinal vessels occlusion and dilatation). Visual field examination revealed bilateral constriction associated with decreased optic nerve fibre layer thickness suggesting optic nerve atrophy. CONCLUSION: This case highlights the need for ophthalmologists to consider the diagnosis of acquired hyperoxaluria in patients with progressive bilateral visual impairment following DLT, especially if the postoperative course is marked by renal failure. Moreover, even after liver-kidney transplantation with a conventional graft, visual function can remain impaired owing to maculopathy and optic atrophy.

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.

Long-term functional outcomes and vision-related quality of life after vitrectomy for epiretinal membrane: a prospective cohort study.

To investigate the long-term effect of unilateral idiopathic epiretinal membrane (uiERM) removal on monocular and binocular visual function, and on vision-related quality of life (VR-QoL). Prospective, single-center study. The following data were collected before and after surgery: distance monocular and binocular best-corrected visual acuity (BCVA), horizontal and vertical metamorphopsia, horizontal and vertical aniseikonia, stereoacuity and National Eye Institute Visual Function Questionnaire-25 item (NEI VFQ-25). Forty-two patients (mean age: 72.7 ± 7.4 years; 24 men) were included. At 6 months postoperatively, distance monocular BCVA (p < 0.001), horizontal metamorphopsia (p = 0.001) and the composite score of NEI VFQ-25 (p < 0.001) significantly improved, in comparison to baseline. At 2 years postoperatively, distance monocular (p < 0.001) and binocular (p = 0.01) BCVA, horizontal (p < 0.001) and vertical (p = 0.02) metamorphopsia, vertical aniseikonia (p = 0.01), stereoacuity (p < 0.001) and 3 subscales scores of the NEI VFQ-25 (p < 0.05) ("general vision", "mental health", "driving") significantly improved in comparison to baseline. Removal of uiERM improves VR-QoL and achieves good visual outcomes on both monocular and binocular visual parameters over long-term. Visual symptoms induced by macular contraction have different improvement kinetics after surgery. Stereopsis, the highest level of binocular vision, can be improved in some cases.