PURPOSE:The aim of this real-world registry study was to evaluate the quality-of-life (QoL) impact of dry eye disease (DED). The specific objectives were to determine factors affecting QoL in DED, and to evaluate the psychometric properties of the Ocular Surface Disease Index (OSDI), Ocular Comfort Index (OCI), and Patient Health Questionnaire (PHQ) in a real-world DED population using modern psychometric methods. METHODS:This descriptive cross-sectional study included 368 DED patients (mean 54.7 ± 16.6 years; 80.2 % female) who completed one or more of the three questionnaires (OSDI, OCI and PHQ). Psychometric analysis of the QoL data was carried out with Andrich's Rating Scale Model of Rasch analysis. RESULTS:The original OSDI and OCI had disordered categories. The Rasch-optimised final QoL scales (OSDI - Overall, OSDI - Symptoms [SY], OSDI - Activity limitation [AL], OSDI - Environmental trigger [EN], OCI Overall, OCI - Frequency [FR], OCI - Intensity [IN], and PHQ) had satisfactory psychometric properties. Patients diagnosed with a mixed aqueous/evaporative DED subtype had worse mean OSDI-Overall and OSDI-AL scores than individuals with evaporative DED (p = 0.012 and 0.001 respectively). Patients with corneal neuropathic pain had worse QoL scores (OSDI-Overall, OSDI-AL, OSDI-SY, OSDI-EN, OCI-Overall, OCI-FR, OCI-IN, and PHQ; all p < 0.05) than those without. Patients who reported undergoing prior treatment or procedure for DED had worse QoL scores than those who did not (all p < 0.05 except for PHQ). The associations between DED signs (tear breakup time and staining) and symptoms were weak or not significant. CONCLUSIONS:In this real-world setting, diagnoses of mixed DED, corneal neuropathic pain, and history of DED treatment/procedures were associated with worse dry eye symptoms, activity limitation, and/or QoL.

RATIONALE:The increasing prevalence of myopia is a growing global public health problem, in terms of rates of uncorrected refractive error and significantly, an increased risk of visual impairment due to myopia-related ocular morbidity. Interventions to slow its progression are needed in childhood, when myopia progression is most rapid. This is a review update, conducted as part of a living systematic review. OBJECTIVES:To assess the comparative efficacy and safety of interventions for slowing myopia progression in children using network meta-analysis (NMA). To generate a relative ranking of interventions according to their efficacy. To produce a brief economic commentary, summarising economic evaluations. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, and three trial registers. The latest search date was 19 February 2024. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) of optical, pharmacological, light therapy and behavioural interventions for slowing myopia progression in children, up to 18 years old. OUTCOMES:Critical outcomes were progression of myopia (mean difference (MD) in the change in spherical equivalent refraction (SER, dioptres (D)), and axial length (AL, mm) in the intervention and control groups at one year or longer), and difference in the change in SER and AL following cessation of treatment (rebound). RISK OF BIAS:We assessed the risk of bias (RoB) for SER and AL using the Cochrane RoB 2 tool. SYNTHESIS METHODS:We followed standard Cochrane methods. We rated the certainty of evidence using the GRADE approach for change in SER and AL at one and two years. We used the surface under the cumulative ranking curve (SUCRA) to rank the interventions for all available outcomes. INCLUDED STUDIES:We included 104 studies (40 new for this update) that randomised 17,509 children, aged 4 years to 18 years. Most studies were conducted in China or other Asian countries (66.3%), and North America (14.4%). Eighty-four studies (80.8%) compared myopia control interventions against inactive controls. Study durations ranged from 12 months to 48 months. SYNTHESIS OF RESULTS:Since most of the networks in the NMA were poorly connected, our estimates are based on direct (pairwise) comparisons, unless stated otherwise. The median change in SER for controls was -0.65 D (55 studies, 4888 participants; one-year follow-up). These interventions may reduce SER progression compared to controls: repeated low intensity red light (RLRL: MD 0.80 D, 95% confidence interval (CI) 0.71 to 0.89; SUCRA = 93.8%; very low-certainty evidence); high-dose atropine (HDA (≥ 0.5%): MD 0.90 D, 95% CI 0.62 to 1.18; SUCRA = 93.3%; moderate-certainty evidence); medium-dose atropine (MDA (0.1% to < 0.5%): MD 0.55 D, 95% CI 0.17 to 0.93; NMA estimate SUCRA = 75.5%; low-certainty evidence); low dose atropine (LDA (< 0.1%): MD 0.25 D, 95% CI 0.16 to 0.35; SUCRA = 53.2%; very low-certainty evidence); peripheral plus spectacle lenses (PPSL: MD 0.45 D, 95% CI 0.16 to 0.74; SUCRA = 50.2%; very low-certainty evidence); multifocal soft contact lenses (MFSCL: MD 0.27 D, 95% CI 0.18 to 0.35; SUCRA = 49.9%; very low-certainty evidence); and multifocal spectacle lenses (MFSL: MD 0.14 D, 95% CI 0.08 to 0.21; SUCRA = 30.8%; low-certainty evidence). The median change in AL for controls was 0.33 mm (58 studies, 9085 participants; one-year follow-up). These interventions may reduce axial elongation compared to controls: RLRL (MD -0.33 mm, 95% CI -0.37 to -0.29; SUCRA = 98.6%; very low-certainty evidence); HDA (MD -0.33 mm, 95% CI -0.35 to -0.30; SUCRA = 88.4%; moderate-certainty evidence); MDA (MD -0.24 mm, 95% CI -0.34 to -0.15; NMA estimate SUCRA = 75.8%; low-certainty evidence); LDA (MD -0.10 mm, 95% CI -0.13 to -0.07; SUCRA = 36.1%; very low-certainty evidence); orthokeratology (ortho-K: MD -0.18 mm, 95% CI -0.21 to -0.14; SUCRA = 79%; moderate-certainty evidence); PPSL (MD -0.13 mm, 95% CI -0.21 to -0.05; SUCRA = 52.6%; very low-certainty evidence); MFSCL (MD -0.11 mm, 95% CI -0.13 to -0.09; SUCRA = 45.6%; low-certainty evidence); and MFSL (MD -0.06 mm, 95% CI -0.09 to -0.04; SUCRA = 26.3%; low-certainty evidence). Ortho-K plus LDA probably reduces axial elongation more than ortho-K monotherapy (MD -0.12 mm, 95% CI -0.15 to -0.09; SUCRA = 81.8%; moderate-certainty evidence). At two-year follow-up, change in SER was reported in 34 studies (3556 participants). The median change in SER for controls was -1.01 D. The ranking of interventions to reduce SER progression was close to that observed at one year; there were insufficient data to draw conclusions on cumulative effects. The highest-ranking interventions were: HAD (SUCRA = 97%); MDA (NMA estimate SUCRA = 69.8%); and PPSL (SUCRA = 69.1%). At two-year follow-up, change in AL was reported in 33 studies (3334 participants). The median change in AL for controls was 0.56 mm. The ranking of interventions to reduce axial elongation was similar to that observed at one year; there were insufficient data to draw conclusions on cumulative effects. The highest-ranking interventions were: ortho-K plus LDA (SUCRA = 94.2%); HAD (SUCRA = 96.8%); and MDA (NMA estimate SUCRA = 88.4%). There was limited evidence on whether cessation of myopia control therapy increases progression beyond the expected rate of progression with age. Adverse events and treatment adherence were not consistently reported. Two studies reported quality of life, showing little to no difference between intervention and control groups. We were unable to draw firm conclusions regarding the relative costs or efficiency of different myopia control strategies in children. AUTHORS' CONCLUSIONS:Most studies compared pharmacological and optical treatments to slow the progression of myopia with an inactive comparator. These interventions may slow refractive change and reduce axial elongation, although results were often heterogeneous. Less evidence is available for two years and beyond; uncertainty remains about the sustained effect of these interventions. Longer term and better quality studies comparing myopia control interventions alone or in combination are needed, with improved methods for monitoring and reporting adverse effects. FUNDING:Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. REGISTRATION:The previous version of this living systematic review is available at doi: 10.1002/14651858.CD014758.pub2.

Importance Anterior-segment optical coherence tomography (AS-OCT) has broad clinical and research utility. The utility of quantitative data derived from AS-OCT is, however, dependent on the quality and consistency of the cumulative evidence base. Objective To develop consensus-based nomenclature that supports standardized reporting of AS-OCT image acquisition and analyses as a foundation to improve research reproducibility. Design, Setting, and Participants A multistage consensus exercise was undertaken, in 2024, with an expert panel of ophthalmologists, optometrists, and vision scientists, informed by a scoping review to identify the range of AS-OCT applications and terminologies in use. Panel members were selected to represent the breadth of clinical areas identified within the review or key stakeholder groups (ie, ocular image acquisition, imaging analysis, consensus methodologies). Nominal group technique was used to seek consensus on existing and newly proposed terminologies for normal anatomical structures identifiable within cross-sectional swept-source and spectral-domain AS-OCT images. An ophthalmic histopathologist then reviewed the output for concordance with histological terminology. Data were analyzed from July 2024 to January 2025. Exposures Expert consensus on nomenclature of ocular structures. Main Outcomes and Measures Agreement on nomenclature of ocular structures, with consensus defined as at least 80% expert agreement. Results A multinational group of 14 experts (mean [SD] age, 46.1 [7.8] years; 10 male [71%]) participated in the consensus process. Scoping review findings resulted in the generation of 45 terms for the annotation of identifiable structures. After presentation of multiple image annotations representing these structures, consensus was reached for 31 terms across 7 images. There was consensus on the use of standardized descriptive terms from the Federative Committee on Anatomical Terminology (FCAT) alongside established eponymous terms. There was absence of consensus on annotations and visualization of structures within less optically accessible areas, such as the episcleral and scleral vasculature. Conclusions and Relevance Results of this survey study describe international, multidisciplinary consensus on terminology for ocular structures identifiable in AS-OCT images and present representative annotated images for reference use. Future expansion of nomenclature and annotation are anticipated, facilitated by advances in imaging technology. Follow-up consensus exercises should consider consensus-based terminology and annotations of pathological structural changes.

AIM:Disease misdiagnosis is more likely if standardised diagnostic criteria are not used. This study systematically examined the effect on diagnosing dry eye disease (DED), when tests for evaluating tear film homeostasis were included or excluded from a multi-test protocol. METHOD:For 1,427 participants across five sites, data for the full suite of diagnostic tests defined in the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) Diagnostic Methodology report algorithm were evaluated; diagnostic sensitivity was calculated when individual signs were removed, and when different combinations of signs were required. RESULTS:Evaluating just one of the three TFOS DEWS II homeostatic signs resulted in between 12.3 % and 36.2 % of patients who met the DED diagnostic criteria not being assigned this diagnosis. While comprehensive ocular surface staining evaluation, comprising of corneal, conjunctival and lid margin staining, in combination with symptoms had the highest sensitivity (87.7 %) of the three markers, the sensitivity dropped to 44.6 % if only corneal staining was evaluated. Omitting either non-invasive tear breakup time or tear osmolarity each dropped the sensitivity by <5 %. The prevalence of DED was substantially reduced if a diagnosis required symptoms and two of the three signs to be present (by 43.7 %-61.2 %) and by 65.9 % if all three signs indicating a loss of tear film homeostasis were required. The outcomes of the analysis did not change significantly across differing severities of DED symptoms. CONCLUSIONS:The TFOS DEWS II diagnostic algorithm of symptoms plus assessing for a tear film (non-invasive tear breakup time or tear osmolarity) and ocular surface sign can be considered a robust and appropriate approach for DED diagnosis.

RATIONALE:Glaucoma is a leading cause of vision loss and blindness, characterized by optic nerve damage and commonly by increased intraocular pressure (IOP). Topical medical therapy is the most common first-line treatment option, yet adherence to these medications is notably low. Improving medication adherence is critical for managing glaucoma effectively. OBJECTIVES:To assess the impact of two or more behavioral interventions (i.e. multifaceted interventions) on topical glaucoma therapy adherence in people utilizing IOP-lowering therapy for at least three months for treating ocular hypertension or glaucoma. SEARCH METHODS:We searched four electronic databases (CENTRAL, MEDLINE, Embase, LILACS), two clinical trial registries, and checked references. The latest search date was 31 May 2024. ELIGIBILITY CRITERIA:We included randomized controlled trials (RCTs) evaluating multifaceted behavioral interventions (≥ 3 months) for topical glaucoma therapy adherence compared with standard care in adults with glaucoma or ocular hypertension. OUTCOMES:Outcomes were change in adherence to topical IOP-lowering medications, change in IOP, optical coherence tomography (OCT) stability, visual field (VF) stability, proportion of participants with disease stability, change in quality of life scores, and adverse events. The time point for these measurements was three months or longer follow-up. We extracted any information related to equity and social determinants of health, and their potential influence on the administration of or outcomes from the interventions. RISK OF BIAS:We assessed the risk of bias for all outcomes reported in the summary of findings tables using the Cochrane risk of bias 2 (RoB 2) tool, except for outcomes where no data were available. SYNTHESIS METHODS:Where possible, we synthesized results for outcomes using random-effects meta-analysis of risk ratios (RRs) for dichotomous outcomes, and mean difference (MD) or standardized mean difference (SMD) for continuous outcomes. Where meta-analysis was not possible due to the available data, we synthesized the results qualitatively following Cochrane-recommended approaches; including summarizing effect estimates and vote counting, accompanied by forest plots to show estimates without meta-analyses and harvest plots. We used the GRADE approach to assess the certainty of the evidence for prespecified outcomes. INCLUDED STUDIES:We included 17 RCTs that enrolled 4536 participants, ranging from 64 to 1800 per study. The mean age of participants ranged from 42 to 76 years. Studies were conducted across North America, Europe, and Asia, with most in the USA (47%). Among 12 studies reporting race and ethnicity, most participants were White (62%), followed by Black (26%), Asian (7%), Hispanic (1%), and others (3%). Follow-up periods ranged from 3 to 24 months. All but one study received financial support from multiple sources. We assessed the risk of bias in 25 outcome measures across 17 studies. We judged one study to be at low risk of bias for both adherence to topical IOP-lowering medications and IOP measures. Four studies reported both outcomes and overall were judged to have some bias concerns, and we judged three studies to have some bias concerns for only adherence. Two studies reported both outcomes with high risk of bias, and another study had a high overall risk of bias for adherence and some concerns for IOP. The remaining nine studies reported adherence only, and we judged these as having some concerns (three studies) or high risk (six studies) of overall bias. SYNTHESIS OF RESULTS:In general, evidence on the effect of multifaceted interventions in improving glaucoma-related outcomes was inconsistent. We conducted an overall meta-analysis of adherent participants that included all comparisons and related subgroups, suggesting any multifaceted intervention may increase the proportion of adherent participants over any control, but the evidence is very uncertain (RR 1.18, 95% confidence interval (CI) 1.01 to 1.38; 8 studies, 2184 participants; I2 = 71%; very low-certainty evidence). Another overall meta-analysis across two comparisons and three subgroups found multifaceted interventions may have little to no improvement on adherence measured by final mean (SMD 0.03, 95% CI -0.19 to 0.09; 4 studies, 758 participants). Qualitatively, vote-counting of estimates showed 14/17 (82%) estimates in favor of multifaceted interventions for improving adherence. Overall, the certainty of the evidence for difference in adherence was 'very low.' We classified included studies into three comparisons: 1. three or more components, composed of education plus two or more (five studies); 2. two components, including education plus one component with or without standard care (11 studies); and 3. two components, including devices plus other with or without standard care (one study). The comparators were standard care or other interventions. Vote-counting for difference in adherence for comparisons 1, 2, and 3 found 5/6 (83%), 8/10 (80%), and 1/1 (100%) estimates favored intervention, respectively. Certainty of the evidence regarding differences in adherence for Comparisons 1, 2, and 3 were 'very low', 'low', and 'low' respectively, primarily due to risk of bias, imprecision, and inconsistency. We had limited and mixed evidence for IOP and VF due to variabilities in outcome measurements across studies and insufficient data. Multifaceted interventions may not result in any IOP or VF improvements. No included studies reported the other prespecified outcome measures. Only five included studies reported whether social determinants of health had any associations with adherence to topical glaucoma medications. The social determinants addressed were race, education level of the participants, marital status, employment status, income level, age, number of chronic diseases, and level of health literacy. Evidence for the influence of these characteristics on intervention effectiveness was mixed. AUTHORS' CONCLUSIONS:Based on very low- and low-certainty evidence identified in this review, it is unclear if multifaceted behavioral interventions have a beneficial effect on patient adherence to topical IOP-lowering medications and IOP in people with ocular hypertension or glaucoma. In most cases, we were unable to conduct meta-analysis due to the diversity of interventions, varying outcome definitions, and inconsistent reporting across studies. Future research would benefit from the adoption of standardized measurements and reporting methods for adherence to medication and clinical outcomes on disease stability, while taking social determinants into account. FUNDING:Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. REGISTRATION:Protocol available via doi.org/10.1002/14651858.CD015788.

RATIONALE:Diffuse distal symmetrical polyneuropathy (DSPN) is a common complication in people living with diabetes mellitus. There is currently no effective treatment for DSPN. There is a biological rationale that omega-3 polyunsaturated fatty acids (PUFAs) may modify peripheral nerve function in DSPN. However, there is a lack of certainty about the potential benefits and harms of omega-3 PUFAs as a treatment for DSPN. OBJECTIVES:To evaluate the benefits and harms of oral omega-3 PUFA supplements as a treatment for DSPN in adults with diabetes mellitus, compared to placebo or no treatment. SEARCH METHODS:We searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two clinical trials registries, together with reference checking, to identify studies eligible for inclusion in the review. The latest search date was 12 June 2024. ELIGIBILITY CRITERIA:We included randomised controlled trials (RCTs) involving adults with type 1 diabetes, type 2 diabetes, or impaired glucose tolerance who had evidence of DSPN, that compared omega-3 PUFA supplements with placebo treatments or no treatment. We excluded studies with an intervention period of less than 180 days. OUTCOMES:Our critical outcome was peripheral neuropathy impairment at six months after treatment. Other main outcomes were: symptoms of peripheral neuropathy, pain, quality of life, and adverse events, including any adverse events; adverse events leading to discontinuation of the intervention; and serious adverse events. We recorded outcomes as change from baseline, or the study endpoint measure, if change from baseline data were not reported. RISK OF BIAS:We used the Cochrane RoB 2 tool to assess bias in the included RCTs. SYNTHESIS METHODS:We synthesised results for each outcome using meta-analysis where possible (inverse variance, random-effects model). Where this was not possible due to the nature of the data, we synthesised the results by summarising effect estimates. We used GRADE to assess the certainty of the body of the evidence for each key outcome. INCLUDED STUDIES:This review included two completed RCTs that collectively involved 87 participants. SYNTHESIS OF RESULTS:Based on findings from one study (43 participants with type 1 diabetes), oral omega-3 PUFA supplementation for six months may have little to no effect on the short-term risk of developing peripheral neuropathy impairment (RR 0.24, 95% CI 0.03 to 1.94; low-certainty evidence), peripheral neuropathy symptoms (MD -0.17, 95% CI -1.36 to 1.02; low-certainty evidence), or health-related quality of life (MD 0.02, 95% CI -0.06 to 0.10; low-certainty evidence), compared to a placebo treatment. From two studies (pooled estimates from outcomes reported for 78 participants), there may be little or no difference between omega-3 PUFA and placebo supplementation with respect to the risk of developing any adverse event (RR 1.03, 95% CI 0.66 to 1.61; P = 0.88; very low-certainty evidence) or a serious adverse event (RR 0.45, 95% CI 0.11 to 1.85; P = 0.27; very low-certainty evidence), but the evidence is very uncertain. The included studies did not report data on pain outcomes or adverse events leading to discontinuation of the treatment. AUTHORS' CONCLUSIONS:There are inadequate data to draw conclusions about the effects of omega-3 PUFA supplementation on peripheral nerve impairment in adults with diabetes mellitus. There may be little to no benefit of oral omega-3 PUFA treatment, compared to placebo or no treatment, for improving peripheral neuropathy symptoms or health-related quality of life. While no harms of omega-3 PUFA treatment are suggested, more data are needed to elucidate any potential risks. FUNDING:This review did not have dedicated funding. REGISTRATION:Protocol available via DOI 10.1002/14651858.CD014623.

Purpose:To characterize corneal immune cell morphodynamics and nerve features, and define the in vivo immune landscape in older adults with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART), relative to healthy age-matched adults. Methods:In this cross-sectional study, 16 HIV-positive individuals receiving ART and 15 age-matched controls underwent ocular surface examinations and functional in vivo confocal microscopy (Fun-IVCM). Time-lapsed videos were created to analyze corneal immune cells (T cells, dendritic cells [DCs], macrophages). Subclinical indicators of corneal health (sensory nerve and endothelial cell features), clinical ocular surface findings, and tear cytokines (analyzed using multiplex bead-based immunoassay) were compared between groups. Results:Participants comprised mostly males (HIV 71 ± 5 years; male:female 15:1; controls 67 ± 6 years; 14:1). The HIV-positive group showed less T-cell motility at the corneal whorl relative to the control group (P = 0.01), and region-dependent differences in T-cell speed (P = 0.001) and DC area (P < 0.001). The HIV-positive group showed greater central corneal nerve fiber width (P = 0.004) and larger endothelial cells (P = 0.02). Clinical findings, corneal immune cell densities, and tear cytokine profiles were similar between groups. Conclusions:Among older individuals with well-controlled HIV infection and clinically-normal ocular surface health, this study identifies subclinical group differences in corneal immune cells (potentially indicative of a heightened, pro-inflammatory activation state in the peripheral cornea) and corneal endothelial cell morphology that parallel those in chronic inflammatory disease. This study demonstrates the utility of Fun-IVCM to evaluate subclinical immune cell features in systemic disease, which could inform the future identification of biomarkers in immune-related conditions.

Membrane contact sites (MCSs) are areas of close proximity between organelles that allow the exchange of material, among other roles. The endoplasmic reticulum (ER) has MCSs with a variety of organelles in the cell. MCSs are dynamic, responding to changes in cell state, and are, therefore, best visualized through inducible labeling methods. However, existing methods typically distort ER-MCSs, by expanding contacts or creating artificial ones. Here, we describe a new method for inducible labeling of ER-MCSs using the Lamin B receptor (LBR) and a generic anchor protein on the partner organelle. Termed LaBeRling, this versatile, one-to-many approach allows labeling of different types of ER-MCSs (mitochondria, plasma membrane, lysosomes, early endosomes, lipid droplets, and Golgi), on-demand, in interphase or mitotic human cells. LaBeRling is nondisruptive and does not change ER-MCSs in terms of the contact number, extent or distance measured; as determined by light microscopy or a deep-learning volume electron microscopy approach. We applied this method to study the changes in ER-MCSs during mitosis and to label novel ER-Golgi contact sites at different mitotic stages in live cells.

Aims: To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy. Methods: This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on in vivo confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay. Results: Mean (f standard deviation) tear NPY concentrations in participants with type 1 diabetes and length- dependent small fibre neuropathy (SFN) was lower than in controls (10.84 f 4.10 ng/mL vs 14.72 f 3.12 ng/mL; p =0.004), but not significantly different from type 1 diabetes participants without SFN (13.39 f 4.66 ng/mL; p =0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non- proliferative DR (10.44 f 3.46 ng/mL) compared to none/minimal DR (13.79 f 4.76 ng/mL; p =0.0005) and controls. In separate linear regression models, both the presence of SFN ((3 =-0.75, p =0.02) and the presence of mild/moderate DR ((3 =-0.84, p =0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations. Conclusions: Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes.

Balanced immune responses in the eyes are crucial to preserve vision. The ocular immune system has long been considered distinct, owing to the so-called 'immune privilege' of its component tissues. More recently, intravital imaging and transcriptomic techniques have reshaped scientific understanding of the ocular immune landscape, such as revealing the specialization of immune cell populations in the various tissues of the eye. As knowledge of the phenotypes of corneal and retinal immune cells has evolved, links to both the systemic immune system, and the central and peripheral nervous systems, have been identified. Using intravital imaging, T cells have recently been found to reside in, and actively patrol, the healthy human cornea. Disease-associated retinal microglia with links to retinal degeneration have also been identified. This Review provides an updated guide to the ocular immune system, highlighting current knowledge of the immune cells that are present in steady-state and specific diseased ocular tissues, as well as evidence for their relationship to systemic disease. In addition, we discuss emerging intravital imaging techniques that can be used to visualize immune cell morphology and dynamics in living human eyes and how these could be applied to advance understanding of the human immune system.

PURPOSE:To determine the efficacy and safety of AZR-MD-001 (0.5 % and 1.0 %) ophthalmic ointment, relative to vehicle, over 3-6 months of treatment, in participants with meibomian gland dysfunction (MGD). METHODS:This was a Phase 2, randomized, vehicle-controlled, multicenter extension clinical trial. Eligible participants were adults with MGD (meibomian gland secretion score (MGS) ≤12 out of 15 glands) who discontinued all other dry eye or MGD treatments. Participants were randomized 1:1:1 to apply AZR-MD-001 1.0 %, 0.5 %, or vehicle to the lower eyelids, twice weekly. Key exploratory endpoints included the least-squared mean difference between groups in the change from baseline in clinical signs (meibomian gland yielding score; MGYLS) and symptoms (Ocular Surface Disease Index; OSDI), at clinic visits at Month 4.5 and 6, and safety measures from 36 months. RESULTS:Participants (66.5 % female) were randomized, at baseline, to AZR-MD-001 0.5 % (n = 82), 1.0 % (n = 83), or vehicle (n = 80). Statistically significant improvements, compared to vehicle, were observed at Month 6 in MGYLS for both AZR-MD-001 groups (0.5 % group: 1.9, 95 % CI 0.9 to 2.8, P = 0.002; 1.0 % group: 1.1, 95 % CI 0.2 to 2.1, P = 0.026), and in OSDI score for the 0.5 % group (-4.5, 95 % CI -8.0 to -0.9, P = 0.0135). The most common adverse events for AZR-MD-001 were application site pain, superficial punctate keratitis and eye pain; most were mild to moderate in severity, and decreased in incidence over time. CONCLUSIONS:AZR-MD-001 (0.5 %) was efficacious in treating signs and symptoms of MGD over six months, with a lower observed incidence of new adverse events over time.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a protein that plays a crucial role in various human organs, including the respiratory and digestive systems. Dysfunctional CFTR is the key variant of the lethal genetic disorder, cystic fibrosis (CF). In the past decade, highly effective CFTR modulator therapies, including elexacaftor-tezacaftor-ivacaftor, have revolutionised CF management by correcting the underlying molecular defect to improve patient outcomes and life expectancy. Despite demonstrating multiorgan efficacy, clinical studies have largely overlooked the potential for ocular disturbances with CFTR modulator therapy, with the exception of a few case studies reporting the presence of crystalline lens pathologies in young children on CFTR modulators, and in breastfed infants born to individuals who were on CFTR modulator treatment during pregnancy. CFTR is present in multiple tissues during embryonic development, including the eye, and its expression can be influenced by genetic and environmental factors. This review summarises the role of CFTR in the eye, and the potential impact of CFTR on eye function and vision later in life. This information provides a framework for understanding the use and possible effects of CFTR-modulating therapeutics in the context of eye health, including the potential to leverage the eye for non-invasive and accessible diagnostic and monitoring capabilities in patients with CF.

In vivo confocal microscopy (IVCM) is a widely used technique for imaging the cornea of the eye with a confocal scanning light ophthalmoscope. Cellular resolution and high contrast are achieved without invasive procedures, suiting the study of living humans. However, acquiring useful image data can be challenging due to the incessant motion of the eye, such that images are typically limited by noise and a restricted field of view. These factors affect the degree to which the same cells can be identified and tracked over time. To redress these shortcomings, here we present a data acquisition protocol together with the details of a free, open-source software package written in Matlab. The software package automatically registers and processes IVCM videos to significantly improve contrast, resolution, and field of view. The software also registers scans acquired at progressive time intervals from the same tissue region, producing a time-lapsed video to facilitate visualization and quantification of individual cell dynamics (e.g., motility and dendrite probing). With minimal user intervention, to date, this protocol has been employed to both cross-sectionally and longitudinally assess the dynamics of immune cells in the human corneal epithelium and stroma, using a technique termed functional in vivo confocal microscopy (Fun-IVCM) in 68 eyes from 68 participants. Using the custom software, registration of 'sequence scan' data was successful in 97% of videos acquired from the corneal epithelium and 93% for the corneal stroma. Creation of time-lapsed videos, in which the averages from single videos were registered across time points, was successful in 93% of image series for the epithelium and 75% of image series for the stroma. The reduced success rate for the stroma occurred due to practical difficulties in finding the same tissue between time points, rather than due to errors in image registration. We also present preliminary results showing that the protocol is well suited to in vivo cellular imaging in the retina with adaptive optics scanning laser ophthalmoscopy (AOSLO). Overall, the approach described here substantially improves the efficiency and consistency of time-lapsed video creation to enable non-invasive study of cell dynamics across diverse tissues in the living eye.