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ChatGPT are deemed more efficient than their human counterparts, these AIs are constrained by their nonspecific and outdated training, no access to current knowledge, generation of plausible-sounding 'fake' responses or hallucinations, inability to process images, lack of critical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.

Exemplifying practice-based research: the influence of age on myopia progression.

CLINICAL RELEVANCE: The electronic storage of patient records and modern-day search engines present private practitioners with a unique opportunity to extract valuable data for investigative research purposes. However, practitioners seldom harness this resource and consequently a vast repository of clinical data remains largely unexplored. BACKGROUND: This study, based on real-world data from an optometric practice, stands as an example of how clinicians can actively contribute to research. In doing so it underscores the role played by age in determining the rate of natural myopia progression. METHODS: A retrospective data analysis of the refractive status, age and optical correction type of participants, was conducted over six years. Forty-four participants were recruited (25 contact lens and 19 spectacle wearers), with a presenting age varying from 5 to 20 years (median, 11 years). Non-cycloplegic, monocular foveal refractions were completed using a ShinNippon open-field autorefractor, corroborated with subjective refraction. The mean spherical equivalent refractive error was calculated for the participants' initial visit (baseline measure) and for a six-year follow-up visit (progression measure), with myopia progression defined as the difference between these measures. Statistical analyses were computed using Decision Tree Analysis, with a significance level set at 95%. RESULTS: The participant age at first visit exerted a significant influence on natural myopia progression over the assessment period (F 1,42 = 17.11, p < 0.001). Individuals aged ≤ 10 years had approximately twice the myopic progression (mean, -2.27 D) of those aged > 10 years (mean, -1.13 D). Neither degree of myopia at the initial visit nor optical correction type had a significant effect on progression (p > 0.05). CONCLUSIONS: Utilizing the advantage of small real-world data samples, the benefit of research by private practitioners was demonstrated, providing evidence that the age at which a child first presents for an eye examination is highly influential in determining their rate of myopia progression.

Optical interventions for myopia control.

A range of optical interventions have been developed to slow the progression of myopia. This review summarizes key studies and their outcomes. Peer-reviewed, randomized controlled clinical trials of at least 18 months duration were identified. Randomized clinical trials were identified and summarised: 13 for spectacles, 5 for overnight orthokeratology, 5 for soft contact lenses, and 3 for orthokeratology combined with low concentration atropine. Overnight orthokeratology trials were the most consistent with 2-year slowing of axial elongation between 0.24 and 0.32 mm. Other modalities were more variable due to the wide range of optical designs. Among spectacle interventions, progressive addition lenses were the least effective, slowing axial elongation and myopia progression by no more than 0.11 mm and 0.31 D, respectively. In contrast, novel designs with peripheral lenslets slow 2-year elongation and progression by up to 0.35 mm and 0.80 D. Among soft contact lens interventions, medium add concentric bifocals slow 3-year elongation and progression by only 0.07 mm and 0.16 D, while a dual-focus design slows 3-year elongation and progression by 0.28 mm and 0.67 D. In summary, all three optical interventions have the potential to significantly slow myopia progression. Quality of vision is largely unaffected, and safety is satisfactory. Areas of uncertainty include the potential for post-treatment acceleration of progression and the benefit of adding atropine to optical interventions.

Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion.

BACKGROUND: Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell antitumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTLs) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion. METHODS: Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic restimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout. RESULTS: Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Antitumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL. CONCLUSIONS: This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short-term augmented effector function against the risk of T cell exhaustion in order to achieve longer-term protection.

Increase in SARS-CoV-2 Seroprevalence in UK Domestic Felids Despite Weak Immunogenicity of Post-Omicron Variants.

Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, the feline immune response to these variants is not well defined. We aimed to estimate the current seroprevalence of SARS-CoV-2 in UK pet cats, as well as characterise the neutralising antibody response to the Omicron (BA.1) variant. A neutralising seroprevalence of 4.4% and an overall seroprevalence of 13.9% was observed. Both purebred and male cats were found to have the highest levels of seroprevalence, as well as cats aged between two and five years. The Omicron variant was found to have a lower immunogenicity in cats than the B.1, Alpha and Delta variants, which reflects previous reports of immune and vaccine evasion in humans. These results further underline the importance of surveillance of SARS-CoV-2 infections in UK cats as the virus continues to evolve.

SARS-CoV-2 in Domestic UK Cats from Alpha to Omicron: Swab Surveillance and Case Reports.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified by active surveillance (1/549, 0.18%), during the Delta wave (1/175, 0.57%). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. These cases demonstrate that, although uncommon in cats, a variety of clinical signs can occur.

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.

Six years of wearer experience in children participating in a myopia control study of MiSight® 1 day.

PURPOSE: To evaluate the experience of children wearing soft contact lenses (CLs) during a trial of MiSight® 1 day (omafilcon A, CooperVision, Inc.), a dual-focus myopia-control daily disposable CL. METHODS: A 3-year, double-masked, randomised trial (Part 1) comparing experiences with MiSight 1 day and a single-vision control (Proclear® 1 day, omafilcon A, CooperVision, Inc.) of neophyte, myopic children (ages 8-12). Treatment (n = 65) and control (n = 70) participants received lenses at sites in Canada, Portugal, Singapore, and the UK. Successful participants completing Part 1 were invited to continue for a further 3 years wearing the dual-focus CL (Part 2), and 85 participants completed the 6-year study. Children and parent questionnaires were conducted at baseline, 1 week, 1 month, and every 6 months until the 60-month visit, with children only also completing questionnaires at 66 and 72 months. RESULTS: Throughout the study, children reported high satisfaction with handling (≥89% top 2 box [T2B]), comfort (≥94% T2B), vision (≥93% T2B for various activities), and overall satisfaction (≥97% T2B). Ratings for comfort and vision were not significantly different between lens groups, visits, or study parts and did not change when children switched to dual-focus CLs. Ratings for 'really easy' or 'kind of easy' application improved from the outset for the neophytes (57% at 1-week follow-up and 85% at 1-month follow-up) and remained high throughout the study (visit: P = 0.007; part: P = 0.0004). Overall satisfaction improved in Part 2 (P = 0.04). Wearing times increased in Part 2 (14 vs. 13 hrs/weekday; 13 vs. 12 hrs/day on weekends; P < 0.001); there were no differences between groups. CONCLUSIONS: Children adapted rapidly to full-time wear, rated lenses highly, and rarely reported issues. The dual-focus optics included in the MiSight® 1 day lenses successfully achieved myopia control without lowering subjective ratings when fitted to neophytes or children refitted from single-vision CLs.

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.

IMI-Nonpathological Human Ocular Tissue Changes With Axial Myopia.

Purpose: To describe nonpathological myopia-related characteristics of the human eye. Methods: Based on histomorphometric and clinical studies, qualitative and quantitative findings associated with myopic axial elongation are presented. Results: In axial myopia, the eye changes from a spherical shape to a prolate ellipsoid, photoreceptor, and retinal pigment epithelium cell density and total retinal thickness decrease, most marked in the retroequatorial region, followed by the equator. The choroid and sclera are thin, most markedly at the posterior pole and least markedly at the ora serrata. The sclera undergoes alterations in fibroblast activity, changes in extracellular matrix content, and remodeling. Bruch's membrane (BM) thickness is unrelated to axial length, although the BM volume increases. In moderate myopia, the BM opening shifts, usually toward the fovea, leading to the BM overhanging into the nasal intrapapillary compartment. Subsequently, the BM is absent in the temporal region (such as parapapillary gamma zone), the optic disc takes on a vertically oval shape, the fovea-optic disc distance elongates without macular BM elongation, the angle kappa reduces, and the papillomacular retinal vessels and nerve fibers straighten and stretch. In high myopia, the BM opening and the optic disc enlarge, the lamina cribrosa, the peripapillary scleral flange (such as parapapillary delta zone) and the peripapillary choroidal border tissue lengthen and thin, and a circular gamma and delta zone develop. Conclusions: A thorough characterization of ocular changes in nonpathological myopia are of importance to better understand the mechanisms of myopic axial elongation, pathological structural changes, and psychophysical sequelae of myopia on visual function.

IMI-Global Trends in Myopia Management Attitudes and Strategies in Clinical Practice-2022 Update.

Purpose: Surveys in 2015 and 2019 identified a high level of eye care practitioner concern/activity about myopia, but the majority still prescribed single vision interventions to young myopes. This research aimed to provide updated information. Methods: A self-administered, internet-based questionnaire was distributed in 13 languages, through professional bodies to eye care practitioners globally. The questions examined awareness of increasing myopia prevalence, perceived efficacy and adoption of available strategies, and reasons for not adopting specific strategies. Results: Of the 3195 respondents, practitioners' concern about the increasing frequency of pediatric myopia in their practices differed between continents (P < 0.001), being significantly higher in Asia (9.0 ± 1.5 of 10) than other continents (range 7.7-8.2; P ≤ 0.001). Overall, combination therapy was perceived by practitioners to be the most effective method of myopia control, followed by orthokeratology and pharmaceutical approaches. The least effective perceived methods were single vision distance undercorrection, spectacles and contact lenses, as well as bifocal spectacles. Practitioners rated their activity in myopia control between (6.6 ± 2.9 in South America to 7.9 ± 1.2/2.2 in Australasia and Asia). Single-vision spectacles are still the most prescribed option for progressing young myopia (32.2%), but this has decreased since 2019, and myopia control spectacles (15.2%), myopia control contact lenses (8.7%) and combination therapy (4.0%) are growing in popularity. Conclusions: More practitioners across the globe are practicing myopia control, but there are still significant differences between and within continents. Practitioners reported that embracing myopia control enhanced patient loyalty, increasing practice revenue and improving job satisfaction.

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.

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis.

Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]). Interpretation: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness. Funding: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

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.

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.