Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection.

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.

Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.

Utility of artificial intelligence-based large language models in ophthalmic care.

PURPOSE: With the introduction of ChatGPT, artificial intelligence (AI)-based large language models (LLMs) are rapidly becoming popular within the scientific community. They use natural language processing to generate human-like responses to queries. However, the application of LLMs and comparison of the abilities among different LLMs with their human counterparts in ophthalmic care remain under-reported. RECENT FINDINGS: Hitherto, studies in eye care have demonstrated the utility of ChatGPT in generating patient information, clinical diagnosis and passing ophthalmology question-based examinations, among others. LLMs' performance (median accuracy, %) is influenced by factors such as the iteration, prompts utilised and the domain. Human expert (86%) demonstrated the highest proficiency in disease diagnosis, while ChatGPT-4 outperformed others in ophthalmology examinations (75.9%), symptom triaging (98%) and providing information and answering questions (84.6%). LLMs exhibited superior performance in general ophthalmology but reduced accuracy in ophthalmic subspecialties. Although AI-based LLMs like ChatGPT are deemed more efficient than their human counterparts, these AIs are constrained by their nonspecific and outdated training, no access to current knowledge, generation of plausible-sounding 'fake' responses or hallucinations, inability to process images, lack of critical literature analysis and ethical and copyright issues. A comprehensive evaluation of recently published studies is crucial to deepen understanding of LLMs and the potential of these AI-based LLMs. SUMMARY: Ophthalmic care professionals should undertake a conservative approach when using AI, as human judgement remains essential for clinical decision-making and monitoring the accuracy of information. This review identified the ophthalmic applications and potential usages which need further exploration. With the advancement of LLMs, setting standards for benchmarking and promoting best practices is crucial. Potential clinical deployment requires the evaluation of these LLMs to move away from artificial settings, delve into clinical trials and determine their usefulness in the real world.

SARS-CoV-2 Seroprevalence and Cross-Variant Antibody Neutralization in Cats, United Kingdom.

Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021-February 2022. The variant-specific response in cats trailed circulating variants in humans, indicating multiple human-to-cat transmissions over a prolonged period.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination.

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Myopia Control Dose Delivered to Treated Eyes by a Dual-focus Myopia-control Contact Lens.

PURPOSE: This study examined the optical impact of a DF contact lens during near viewing in a sample of habitual DF lens wearing children. METHODS: Seventeen myopic children aged 14 to 18 years who had completed 3 or 6 years of treatment with a DF contact lens (MiSight 1 Day; CooperVision, Inc., San Ramon, CA) were recruited and fit bilaterally with the DF and a single-vision (Proclear 1 Day; CooperVision, Inc.) contact lens. Right eye wavefronts were measured using a pyramidal aberrometer (Osiris; CSO, Florence, Italy) while children accommodated binocularly to high-contrast letter stimuli at five target vergences. Wavefront error data were used to compute pupil maps of refractive state. RESULTS: During near viewing, children wearing single-vision lenses accommodated on average to achieve approximate focus in the pupil center but, because of combined accommodative lag and negative spherical aberration, experienced up to 2.00 D of hyperopic defocus in the pupil margins. With DF lenses, children accommodated similarly achieving approximate focus in the pupil center. When viewing three near distances (0.48, 0.31, and 0.23 m), the added +2.00 D within the DF lens treatment optics shifted the mean defocus from +0.75 to -1.00 D. The DF lens reduced the percentage of hyperopic defocus (≥+0.75 D) in the retinal image from 52 to 25% over these target distances, leading to an increase in myopic defocus (≤-0.50 D) from 17 to 42%. CONCLUSIONS: The DF contact lens did not alter the accommodative behavior of children. The treatment optics introduced myopic defocus and decreased the amount of hyperopically defocused light in the retinal image.

Conformation of the anterior segment in human myopia.

PURPOSE: Topography of the in vivo anterior segment is of relevance in understanding its role in myopia and in the development of ocular surgical procedures. Using 3D magnetic resonance (MR) images of the human eye, regional variations in surface area (SA) and bulbosity of four anterior segment regions were investigated in association with refractive status (Rx), axial length (AL) and total ocular volume (OV). METHODS: T2-weighted ocular MR images from 43 adults aged 18-40 years (mean ± SD; 28.65 ± 6.20) comprising 20 non-myopes (≥-0.50) 0.57 ± 1.38 and 23 myopes (<-0.50) -6.37 ± 4.23 MSE (D) were collected. 2D representations of each quadrant (superior-temporal [ST], superior-nasal [SN], inferior-temporal [IT] and inferior-nasal [IN]) of the anterior section (3.5-9 mm) were fitted with second-order polynomials. Polynomials were integrated and rotated about the x-axis to generate SA; dividing the SA by 4 provided relative quadrantial SA. The x2 coefficient provides indices of bulbosity. OV was derived from the 3D MRI scans. Rx and AL were measured using cycloplegic autorefraction and the Zeiss IOLMaster, respectively. One- and two-way repeated-measures ANCOVAs tested differences in SA and bulbosity for Rx, gender, ethnicity and age. Pearson's correlation coefficient tested the relationship between MRI-derived metrics and biometry. RESULTS: Significant differences in SA were observed between quadrants (p < 0.001) with differences between ST versus IN, IN versus IT and SN versus IT. An interaction effect (p = 0.01) for Rx suggested smaller temporal (ST and IT) and larger nasal (SN and IN) SA in myopes. AL and myopic Rx were negative correlated (p < 0.05) with SA at IN, SN and IT. OV was significantly associated with SA at ST. Bulbosity showed no regional differences nor an effect of AL or Rx. CONCLUSION: Significant regional variation in SA exists across the anterior segment that is modulated by Rx and AL. It is unclear whether these structural characteristics are a precursor or consequence of myopia and may warrant investigation when developing biomechanical interventions.

Effect of peripheral defocus on axial growth and modulation of refractive error in children with anisohyperopia.

PURPOSE: To establish whether axial growth and refractive error can be modulated in anisohyperopic children by imposing relative peripheral hyperopic defocus (RPHD) using multifocal soft contact lenses. METHODS: This study is a prospective, controlled paired-eye study with anisohyperopic children. Axial growth and refractive error were observed without intervention for the first 6 months of the 3-year trial with participants wearing single vision spectacles. Then, participants wore a centre-near, multifocal, soft contact lens (+2.00 D add) in their more hyperopic eye for 2 years, with a single vision contact lens worn in the fellow eye if required. The 'centre-near' portion of the contact lens in the more hyperopic eye corrected distance refractive error while the 'distance' portion imposed hyperopic defocus in the peripheral retina. Participants reverted to single vision spectacles for the final 6 months. RESULTS: Eleven participants, mean age of 10.56 years (SD 1.43; range 8.25-13.42), completed the trial. No increase in axial length (AL) was found during the first 6 months in either eye (p > 0.99). Axial growth across the 2-year intervention period was 0.11 mm (SEM 0.03; p = 0.06) in the test eye versus 0.15 mm (SEM 0.03; p = 0.003) in the control eye. AL was invariant during the final 6 months in both eyes (p > 0.99). Refractive error was stable during the first 6 months in both eyes (p = 0.71). Refractive error change across the 2-year intervention period was -0.23 D (SEM 0.14; p = 0.32) in the test eye versus -0.30 D (SEM 0.14; p = 0.61) in the control eye. Neither eye demonstrated a change in refractive error during the final 6 months (p > 0.99). CONCLUSIONS: Imposing RPHD using the centre-near, multifocal, contact lens specified here did not accelerate axial growth nor reduce refractive error in anisohyperopic children.

Assessing the utility of ChatGPT as an artificial intelligence-based large language model for information to answer questions on myopia.

PURPOSE: ChatGPT is an artificial intelligence language model, which uses natural language processing to simulate human conversation. It has seen a wide range of applications including healthcare education, research and clinical practice. This study evaluated the accuracy of ChatGPT in providing accurate and quality information to answer questions on myopia. METHODS: A series of 11 questions (nine categories of general summary, cause, symptom, onset, prevention, complication, natural history, treatment and prognosis) were generated for this cross-sectional study. Each question was entered five times into fresh ChatGPT sessions (free from influence of prior questions). The responses were evaluated by a five-member team of optometry teaching and research staff. The evaluators individually rated the accuracy and quality of responses on a Likert scale, where a higher score indicated greater quality of information (1: very poor; 2: poor; 3: acceptable; 4: good; 5: very good). Median scores for each question were estimated and compared between evaluators. Agreement between the five evaluators and the reliability statistics of the questions were estimated. RESULTS: Of the 11 questions on myopia, ChatGPT provided good quality information (median scores: 4.0) for 10 questions and acceptable responses (median scores: 3.0) for one question. Out of 275 responses in total, 66 (24%) were rated very good, 134 (49%) were rated good, whereas 60 (22%) were rated acceptable, 10 (3.6%) were rated poor and 5 (1.8%) were rated very poor. Cronbach's α of 0.807 indicated good level of agreement between test items. Evaluators' ratings demonstrated 'slight agreement' (Fleiss's κ, 0.005) with a significant difference in scoring among the evaluators (Kruskal-Wallis test, p < 0.001). CONCLUSION: Overall, ChatGPT generated good quality information to answer questions on myopia. Although ChatGPT shows great potential in rapidly providing information on myopia, the presence of inaccurate responses demonstrates that further evaluation and awareness concerning its limitations are crucial to avoid potential misinterpretation.

Distemper, extinction, and vaccination of the Amur tiger.

Canine distemper virus (CDV) has recently emerged as an extinction threat for the endangered Amur tiger (Panthera tigris altaica). CDV is vaccine-preventable, and control strategies could require vaccination of domestic dogs and/or wildlife populations. However, vaccination of endangered wildlife remains controversial, which has led to a focus on interventions in domestic dogs, often assumed to be the source of infection. Effective decision making requires an understanding of the true reservoir dynamics, which poses substantial challenges in remote areas with diverse host communities. We carried out serological, demographic, and phylogenetic studies of dog and wildlife populations in the Russian Far East to show that a number of wildlife species are more important than dogs, both in maintaining CDV and as sources of infection for tigers. Critically, therefore, because CDV circulates among multiple wildlife sources, dog vaccination alone would not be effective at protecting tigers. We show, however, that low-coverage vaccination of tigers themselves is feasible and would produce substantive reductions in extinction risks. Vaccination of endangered wildlife provides a valuable component of conservation strategies for endangered species.

SARS-CoV-2 Evolution and Patient Immunological History Shape the Breadth and Potency of Antibody-Mediated Immunity.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralization responses against SARS-CoV-2Wuhan, SARS-CoV-2α, SARS-CoV-2δ, and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2α, or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.

Neutralizing antibodies provide protection against viruses and are generated because of vaccination or prior infections. The main target of anti-SARS-CoV-2 neutralizing antibodies is a protein called spike, which decorates the viral particle and mediates viral entry into cells. As SARS-CoV-2 evolves, mutations accumulate in the spike protein, allowing the virus to escape antibody-mediated immunity and decreasing vaccine effectiveness. Multiple SARS-CoV-2 variants have appeared since the start of the COVID-19 pandemic, causing various waves of infection through the population and infecting­in some cases­people that had been previously infected or vaccinated. Because the antibody response is highly specific, individuals infected with different variants are likely to have different repertoires of neutralizing antibodies. We studied the breadth and potency of the antibody-mediated response against different SARS-CoV-2 variants using sera from vaccinated people as well as from people infected with different variants. We show that potency of the antibody response against different SARS-CoV-2 variants depends on the particular variant that infected each person, the exposure type (infection or vaccination) and the number and order of exposures. Our study provides insight into the interplay between virus evolution and immunity, as well as important information for the development of better vaccination strategies.

Long-term Effect of Dual-focus Contact Lenses on Myopia Progression in Children: A 6-year Multicenter Clinical Trial.

SIGNIFICANCE: Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a 6-year period. Significant slowing was also observed in children switched from a single vision control to treatment lenses (3 years in each lens). PURPOSE: This study aimed to evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period and assess myopia progression in children who were switched to a DFCL at the end of year 3. METHODS: Part 1 was a 3-year clinical trial comparing DFCLs with a control contact lens (Proclear 1 day) at four investigational sites. In part 2, subjects completing part 1 were invited to continue for 3 additional years during which all children were treated with MiSight 1 day DFCLs (52 and 56 from the initially treated [T6] and control [T3] groups, respectively). Eighty-five subjects (45 [T3] and 40 [T6]) completed part 2. Cyclopleged spherical equivalent refractive errors (SEREs) and axial lengths (ALs) were monitored, and a linear mixed model was used to compare their adjusted change annually. RESULTS: Average ages at part 2 baseline were 13.2 ± 1.3 and 13.0 ± 1.5 years for the T6 and T3 groups, respectively. Slowed myopia progression in the T6 group observed during part 1 was sustained throughout part 2 (mean ± standard error of the mean: change from baseline SERE [in diopters], -0.52 ± 0.076 vs. -0.51 ± 0.076; change in AL [in millimeters], 0.28 ± 0.033 vs. 0.23 ± 0.033; both P > .05). Comparing progression rates in part 2 for the T6 and T3 groups, respectively, indicates that prior treatment does not influence efficacy (SERE, -0.51 ± 0.076 vs. -0.34 ± 0.077; AL, 0.23 ± 0.03 vs. 0.18 ± 0.03; both P > .05). Within-eye comparisons of AL growth revealed a 71% slowing for the T3 group (3 years older than part 1) and further revealed a small subset of eyes (10%) that did not respond to treatment. CONCLUSIONS: Dual-focus soft contact lenses continue to slow the progression of myopia in children over a 6-year period revealing an accumulation of treatment effect. Eye growth of the initial control cohort with DFCL was slowed by 71% over the subsequent 3-year treatment period.

Size and position of the optic disc crescent in a white European population with myopia.

SIGNIFICANCE: One of the first clinically observed changes in the retina with progressing myopia is in the form of optic disc crescents. If such a change is predictive of myopia progression, it could aid in myopia management interventions to target those at greatest risk of progression and subsequent ocular morbidity. PURPOSE: To investigate the type, dimension and appearance of optic disc crescents and how they relate to the level of myopia. METHODS: Retrospective data collection analysing retinal photographs of healthy children and adults with a refractive error of ≤-0.50 D sphere and astigmatism ≤2.00 D. Crescent location, maximum crescent width and vertical disc diameter were measured from retinal images of right eyes only. RESULTS: Four-hundred eyes with a mean spherical error (SER) of -0.50 to -14.00 D (aged 7-81 years) were included (83.5% exhibited a discernible crescent). Mean (SD) maximum crescent width was 0.24 (0.24) mm. Univariate analysis showed a significant correlation between crescent width and age (r = 0.26, p < 0.001). SER was correlated with crescent width when controlling for age (r = -0.45, p < 0.001) and to the ratio of crescent width to vertical disc diameter (r = -0.43, p < 0.001). Temporal crescents were the most frequently observed (74%), followed by inferior temporal crescents (17%). One-way between-groups analysis of variance showed a significant difference between crescent locations (F = 5.2, p < 0.001). Post-hoc analysis revealed significant differences in SER between those with no crescent versus an inferior-temporal crescent, as well as differences between those with temporal versus inferior-temporal crescents. Other crescent locations did not differ significantly in the level of myopia. Participants not exhibiting a crescent had the lowest level of myopia (mean [SD] -3.03 [1.97)] D), while those with inferior temporal crescents had a mean (SD) SER of -5.01 (2.37) D. CONCLUSION: In this white European population, higher levels of SER were associated with increasing crescent size. Eyes with inferior temporally located crescents were more myopic.

The effect of peripheral defocus on axial growth and modulation of refractive error in hyperopes.

PURPOSE: To establish whether axial growth and refractive error can be modulated in hyperopic children by imposing relative peripheral hyperopic defocus using multifocal soft contact lenses. METHODS: A prospective controlled study with hyperopic participants allocated to a control or test group. Control group participants were corrected with single vision spectacles and changes to axial length and refractive error were followed for 3 years. For the test group, axial growth and post-cycloplegic refractive error were observed with participants wearing single vision spectacles for the first 6 months of the trial and then corrected with centre-near multifocal soft contact lenses with a 2.00 D add for 2 years. The central 'near' portion of the contact lens corrected distance refractive error while the 'distance' portion imposed hyperopic defocus. Participants reverted to single vision spectacles for the final 6 months of the study. RESULTS: Twenty-two participants, mean age 11.13 years (SD 1.72) (range 8.33-13.92), completed the trial. Axial length did not change during the first 6 months in either group (p = 1.00). Axial growth across the 2-year intervention period was 0.17 mm (SEM 0.04) (p < 0.0005) in the test group versus 0.06 mm (SEM 0.07) (p = 0.68) in the control group. Axial length was invariant during the final 6 months in either group (p = 1.00). Refractive error was stable during the first 6 months in both groups (p = 1.00). Refractive error change across the 2-year intervention period was -0.26 D (SEM 0.14) (p = 0.38) in the test group versus -0.01 D (SEM 0.09) (p = 1.00) in the control group. Neither the test (p = 1.00) nor control (p = 0.63) group demonstrated a change in refractive error during the final 6 months. CONCLUSIONS: The rate of axial growth can be accelerated in children with hyperopia using centre-near multifocal soft contact lenses.

Severe Acute Respiratory Syndrome Coronavirus 2 Serosurveillance in a Patient Population Reveals Differences in Virus Exposure and Antibody-Mediated Immunity According to Host Demography and Healthcare Setting.

Identifying drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient serum samples showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralization assays showed that highly neutralizing antibodies developed in about half of individuals who tested positive with enzyme-linked immunosorbent assay, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, male patients, and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralization activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves.

Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection.

Ym1 and RELMα are established effector molecules closely synonymous with Th2-type inflammation and associated pathology. Here, we show that whilst largely dependent on IL-4Rα signaling during a type 2 response, Ym1 and RELMα also have IL-4Rα-independent expression patterns in the lung. Notably, we found that Ym1 has opposing effects on type 2 immunity during nematode infection depending on whether it is expressed at the time of innate or adaptive responses. During the lung migratory stage of Nippostrongylus brasiliensis, Ym1 promoted the subsequent reparative type 2 response but once that response was established, IL-4Rα-dependent Ym1 was important for limiting the magnitude of type 2 cytokine production from both CD4+ T cells and innate lymphoid cells in the lung. Importantly, our study demonstrates that delivery of Ym1 to IL-4Rα deficient animals drives RELMα production and overcomes lung repair deficits in mice deficient in type 2 immunity. Together, Ym1 and RELMα, exhibit time and dose-dependent interactions that determines the outcome of lung repair during nematode infection.

In vivo measures of anterior scleral resistance in humans with rebound tonometry.

PURPOSE: To measure regional variations in anterior scleral resistance (ASR) using a ballistic rebound tonometer (RBT) and examine whether the variations are significantly affected by ethnicity and refractive error (RE). METHODS: ASR was measured using a RBT (iCare TA01) following calibration against the biomechanical properties of agarose biogels. Eight scleral regions (nasal, temporal, superior, inferior, inferior-nasal, inferior-temporal, superior-nasal and superior-temporal) were measured at locations 4mm from the limbus. Subjects were 130 young adults comprising three ethnic groups whose RE distributions [MSE (D) ± S.D.] incorporated individuals categorised as without-myopia (NM; MSE ≥ -0.50) and with-myopia (WM; MSE < -0.50); British-White (BW): 26 NM + 0.52 ± 1.15D; 22 WM -3.83 ± 2.89D]; British-South-Asian (BSA): [9 NM + 0.49 ± 1.06D; 11 WM -5.07 ± 3.76D; Hong-Kong-Chinese (HKC): [11 NM + 0.39 ± 0.66D; 49 WM -4.46 ± 2.70D]. Biometric data were compiled using cycloplegic open-field autorefraction and the Zeiss IOLMaster. Two- and three-way repeated measures analysis of variances (anovas) tested regional differences for RBT values across both refractive status and ethnicity whilst stepwise forward multiple linear regression was used as an exploratory test. RESULTS: Significant regional variations in ASR were identified for the BW, BSA and HKC (p < 0.001) individuals; superior-temporal region showed the lowest levels of resistance whilst the inferior-nasal region the highest. Compared to the BW and BSA groups, the HKC subjects displayed a significant increase in mean resistance for each respective region (p < 0.001). With the exception of the inferior region, ethnicity was found to be the chief predictor for variation in the scleral RBT values for all other regions. Mean RE group differences were insignificant. CONCLUSIONS: The novel application of RBT to the anterior sclera confirm regional variation in ASR. Greater ASR amongst the HKC group than the BW and BSA individuals suggests that ethnic differences in anterior scleral biomechanics may exist.

Western Australia Atropine for the Treatment of Myopia (WA-ATOM) study: Rationale, methodology and participant baseline characteristics.

IMPORTANCE: Atropine eyedrops are a promising treatment for slowing myopia progression in East Asian children. However, its effects on children in Australia, including those of non-Asian background, have not been well-studied. BACKGROUND: The Western Australia Atropine for the Treatment of Myopia (WA-ATOM) study aims to determine the efficacy and long-term effects of low-dose atropine eyedrops in myopia control. This paper describes the study rationale, methodology and participant baseline characteristics. DESIGN: Single-centre, double-masked, randomized controlled trial. PARTICIPANTS: Children (6-16 years) with spherical equivalent ≤-1.50 D in each eye, astigmatism ≤1.50 D and myopia progression by ≥0.50 D/year. METHODS: Enrolled children were randomly assigned 2:1 to receive 0.01% atropine or placebo eyedrops. Participants are examined every 6 months during first 3 years of the study (2-year treatment phase followed by a 1-year washout phase), and then at a 5-year follow-up (2 years after the end of the washout phase). MAIN OUTCOME MEASURES: Annual progression rate of myopia and axial length, tolerability to eyedrops and incidence and severity of unwanted effects. RESULTS: Out of 311 children who were referred, 242 were suitable for study participation, and 153 were subsequently enrolled. The baseline characteristics of enrolled participants are presented. CONCLUSIONS AND RELEVANCE: Outcomes of the WA-ATOM study will inform on the efficacy, tolerability, safety and long-term effects of low-dose atropine eyedrops in myopia control in Australian children. The impact of ocular sun exposure, iris colour and parental myopia on the efficacy of low-dose atropine will also be assessed.

Structure-Guided Identification of a Nonhuman Morbillivirus with Zoonotic Potential.

Morbilliviruses infect a broad range of mammalian hosts, including ruminants, carnivores, and humans. The recent eradication of rinderpest virus (RPV) and the active campaigns for eradication of the human-specific measles virus (MeV) have raised significant concerns that the remaining morbilliviruses may emerge in so-called vacated ecological niches. Seeking to assess the zoonotic potential of nonhuman morbilliviruses within human populations, we found that peste des petits ruminants virus (PPRV)-the small-ruminant morbillivirus-is restricted at the point of entry into human cells due to deficient interactions with human SLAMF1-the immune cell receptor for morbilliviruses. Using a structure-guided approach, we characterized a single amino acid change, mapping to the receptor-binding domain in the PPRV hemagglutinin (H) protein, which overcomes this restriction. The same mutation allowed escape from some cross-protective, human patient, anti-MeV antibodies, raising concerns that PPRV is a pathogen with zoonotic potential. Analysis of natural variation within human and ovine SLAMF1 also identified polymorphisms that could correlate with disease resistance. Finally, the mechanistic nature of the PPRV restriction was also investigated, identifying charge incompatibility and steric hindrance between PPRV H and human SLAMF1 proteins. Importantly, this research was performed entirely using surrogate virus entry assays, negating the requirement for in situ derivation of a human-tropic PPRV and illustrating alternative strategies for identifying gain-of-function mutations in viral pathogens.IMPORTANCE A significant proportion of viral pandemics occur following zoonotic transmission events, where animal-associated viruses jump species into human populations. In order to provide forewarnings of the emergence of these viruses, it is necessary to develop a better understanding of what determines virus host range, often at the genetic and structural levels. In this study, we demonstrated that the small-ruminant morbillivirus, a close relative of measles, is unable to use human receptors to enter cells; however, a change of a single amino acid in the virus is sufficient to overcome this restriction. This information will be important for monitoring this virus's evolution in the field. Of note, this study was undertaken in vitro, without generation of a fully infectious virus with this phenotype.