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Rationale and Objective: Cystic fibrosis (CF) is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators offer significant improvements, but approximately 10% of patients remain nonresponsive or are intolerant. This study provides an analysis of rSIV.F/HN, a lentiviral vector optimized for lung delivery, including CFTR protein expression, functional correction of CFTR defects and genomic integration site analysis in preparation for a first-in-human clinical trial., Methods: Air-liquid interface cultures of primary human bronchial epithelial cells (HBEC) from CF patients (F508del/F508del), as well as a CFTR-deficient immortalized human lung epithelial cell line mimicking Class I (CFTR-null) homozygous mutations, were used to assess transduction efficiency. Quantification methods included a novel proximity ligation assay (PLA) for CFTR protein expression. For assessment of CFTR channel activity, Ussing chamber studies were conducted. The safety profile was assessed using integration site analysis and in vitro insertional mutagenesis studies., Results: rSIV.F/HN expressed CFTR and restored CFTR-mediated chloride currents to physiological levels in primary F508del/F508del HBECs as well as in a Class I cells. In contrast, the latter could not be achieved by small-molecule CFTR modulators, underscoring the potential of gene therapy for this mutation class. Combination of rSIV.F/HN-CFTR with the potentiator ivacaftor showed a greater than additive effect. The genomic integration pattern showed no site predominance (frequency of occurrence ≤10%), and a low risk of insertional mutagenesis was observed in an in vitro immortalization assay., Conclusions: The results underscore rSIV.F/HN as a promising gene therapy vector for CF, providing a mutation-agnostic treatment option., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Research assuming linearity has concluded that corneal biomechanics are compromised in high myopia. We investigated whether this assumption was appropriate and re-examined these associations across different levels of myopia., Methods: Myopic (spherical equivalent refraction, SER ≤ -0.50 D) eyes of 10,488 adults aged 40-69 years without any history of systemic and ocular conditions were identified in the UK Biobank. Ordinary least squares (OLS) regression was employed to test the linear association between corneal hysteresis (CH) or corneal resistance factor (CRF), separately, and SER while controlling for age, sex, corneal radius and intraocular pressure. Quantile regression (QR) was used to test the same set of associations across 49 equally spaced conditional quantiles of SER., Results: In OLS regression, each standard deviation (SD) decrease in CH and CRF was associated with 0.08 D (95% CI: 0.04-0.12; p < 0.001) and 0.10 D (95% CI: 0.04-0.15; p < 0.001) higher myopia, respectively. However, residual analysis indicated that the linearity assumption was violated. QR revealed no evidence of a significant association between CH/CRF and SER in low myopia, but a significant (p < 0.05) positive association became evident from -2.78 D (0.06 and 0.08 D higher myopia per SD decrease in CH and CRF). The magnitude of association increased exponentially with increasing myopia: in the -5.03 D quantile, every SD decrease in CH and CRF was associated with 0.17 D (95% CI: 0.08-0.25; p < 0.001) and 0.21 D (95% CI: 0.10-0.31; p < 0.001) higher myopia. In the -8.63 D quantile, this further increased to 0.54 D (95% CI: 0.33-0.76; p < 0.001) and 0.67 D (95% CI: 0.41-0.93; p < 0.001) higher myopia per SD decrease in CH and CRF., Conclusions: Corneal biomechanics appeared compromised from around -3.00 D. These changes were observed to be exponential with increasing myopia., (© 2024 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM) classification framework., Methods: Findings from six longitudinal studies (5-18 years) were narratively synthesised and meta-analysed, using odds ratio (OR) as the common measure of association. All studies adjusted for baseline myopia, age and sex at a minimum. The quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation framework., Results: Five out of six studies were conducted in Asia. There was inconclusive evidence of an independent effect (or lack thereof) of ethnicity and sex on PM onset/progression. The odds of PM onset increased with greater axial length (pooled OR: 2.03; 95% CI: 1.71-2.40; p < 0.001), older age (pooled OR: 1.07; 1.05-1.09; p < 0.001) and more negative spherical equivalent refraction, SER (OR: 0.77; 0.68-0.87; p < 0.001), all of which were supported by an acceptable level of evidence. Fundus tessellation was found to independently increase the odds of PM onset in a population-based study (OR: 3.02; 2.58-3.53; p < 0.001), although this was only supported by weak evidence. There was acceptable evidence that greater axial length (pooled OR: 1.23; 1.09-1.39; p < 0.001), more negative SER (pooled OR: 0.87; 0.83-0.92; p < 0.001) and higher education level (pooled OR: 3.17; 1.36-7.35; p < 0.01) increased the odds of PM progression. Other baseline factors found to be associated with PM progression but currently supported by weak evidence included age (pooled OR: 1.01), severity of myopic maculopathy (OR: 3.61), intraocular pressure (OR: 1.62) and hypertension (OR: 0.21)., Conclusions: Most PM risk/prognostic factors are not supported by an adequate evidence base at present (an indication that PM remains understudied). Current factors for which an acceptable level of evidence exists (limited in number) are unmodifiable in adults and lack personalised information. More longitudinal studies focusing on uncovering modifiable factors and imaging biomarkers are warranted., (© 2024 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index., Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centered region of interest. We analyzed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error [MAE]) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error., Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703), and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal)/0.9831, 0.9779, 0.7948 (external), respectively (all P < 0.0001). Choroidalyzer's agreement with graders was comparable to the intergrader agreement across all metrics., Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully automatic methods like Choroidalyzer could provide objectivity and standardization.

Purpose: To investigate whether fractal dimension (FD)-based oculomics could be used for individual risk prediction by evaluating repeatability and robustness., Methods: We used two datasets: "Caledonia," healthy adults imaged multiple times in quick succession for research (26 subjects, 39 eyes, 377 color fundus images), and GRAPE, glaucoma patients with baseline and follow-up visits (106 subjects, 196 eyes, 392 images). Mean follow-up time was 18.3 months in GRAPE; thus it provides a pessimistic lower bound because vasculature could change. FD was computed with DART and AutoMorph. Image quality was assessed with QuickQual, but no images were initially excluded. Pearson, Spearman, and intraclass correlation (ICC) were used for population-level repeatability. For individual-level repeatability, we introduce measurement noise parameter λ, which is within-eye standard deviation (SD) of FD measurements in units of between-eyes SD., Results: In Caledonia, ICC was 0.8153 for DART and 0.5779 for AutoMorph, Pearson/Spearman correlation (first and last image) 0.7857/0.7824 for DART, and 0.3933/0.6253 for AutoMorph. In GRAPE, Pearson/Spearman correlation (first and next visit) was 0.7479/0.7474 for DART, and 0.7109/0.7208 for AutoMorph (all P < 0.0001). Median λ in Caledonia without exclusions was 3.55% for DART and 12.65% for AutoMorph and improved to up to 1.67% and 6.64% with quality-based exclusions, respectively. Quality exclusions primarily mitigated large outliers. Worst quality in an eye correlated strongly with λ (Pearson 0.5350-0.7550, depending on dataset and method, all P < 0.0001)., Conclusions: Repeatability was sufficient for individual-level predictions in heterogeneous populations. DART performed better on all metrics and might be able to detect small, longitudinal changes, highlighting the potential of robust methods.

Purpose: To quantitatively characterize retinal changes across different quantiles of refractive error in 34,414 normal eyes of 23,064 healthy adults in the UK Biobank., Methods: Twelve optic disc (OD), foveal and vascular parameters were derived from color fundus photographs, correcting for ocular magnification as appropriate. Quantile regression was used to test the independent associations between these parameters and spherical equivalent refraction (SER) across 34 refractive quantiles (high hyperopia to high myopia)-controlling for age, sex and corneal radius., Results: More negative SER was nonlinearly associated with greater Euclidian (largely horizontal) OD-fovea distance, larger OD, less circular OD, more obliquely orientated OD (superior pole tilted towards the fovea), brighter fovea, lower vascular complexity, less tortuous vessels, more concave (straightened out towards the fovea) papillomacular arterial/venous arcade and wider central retinal arterioles/venules. In myopia, these parameters varied more strongly with SER as myopia increased. For example, while every standard deviation (SD) decrease in vascular complexity was associated with 0.63 D (right eye: 95% confidence interval [CI], 0.58-0.68) to 0.68 D (left eye: 95% CI, 0.63-0.73) higher myopia in the quantile corresponding to -0.60 D, it was associated with 1.61 D (right eye: 95% CI, 1.40-1.82) to 1.70 D (left eye: 95% CI, 1.56-1.84) higher myopia in the most myopic quantile. OD-fovea angle (degree of vertical separation between OD and fovea) was found to vary linearly with SER, but the magnitude was of little practical importance (less than 0.10 D variation per SD change in angle in almost all refractive quantiles) compared with the changes in OD-fovea distance., Conclusions: Several interrelated retinal changes indicative of an increasing (nonconstant) rate of mechanical stretching are evident at the posterior pole as myopia increases. These changes also suggest that the posterior pole stretches predominantly in the temporal horizontal direction.

Purpose: To investigate whether fractal dimension (FD), a retinal trait relating to vascular complexity and a potential "oculomics" biomarker for systemic disease, is applicable to a mixed-age, primary-care population., Methods: We used cross-sectional data (96 individuals; 183 eyes; ages 18-81 years) from a university-based optometry clinic in Glasgow, Scotland, to study the association between FD and systemic health. We computed FD from color fundus images using Deep Approximation of Retinal Traits (DART), an artificial intelligence-based method designed to be more robust to poor image quality., Results: Despite DART being designed to be more robust, a significant association (P < 0.001) between image quality and FD remained. Consistent with previous literature, age was associated with lower FD (P < 0.001 univariate and when adjusting for image quality). However, FD variance was higher in older patients, and some patients over 60 had FD comparable to those of patients in their 20s. Prevalent systemic conditions were significantly (P = 0.037) associated with lower FD when adjusting for image quality and age., Conclusions: Our work suggests that FD as a biomarker for systemic health extends to mixed-age, primary-care populations. FD decreases with age but might not substantially decrease in everyone. This should be further investigated using longitudinal data. Finally, image quality was associated with FD, but it is unclear whether this finding is measurement error caused by image quality or confounded by age and health. Future work should investigate this to clarify whether adjusting for image quality is appropriate., Translational Relevance: FD could potentially be used in regular screening settings, but questions around image quality remain.

Objectives: To investigate the association between intraocular pressure (IOP) and axial elongation rate in highly myopic children from the ZOC-BHVI High Myopia Cohort Study., Methods: 162 eyes of 81 healthy children (baseline spherical equivalent: -6.25 D to -15.50 D) aged 7-12 years with non-pathological high myopia were studied over five biennial visits. The mean (SD) follow-up duration was 5.2 (3.3) years. A linear mixed-effects model (LMM) was used to assess the association between IOP (at time point t-1) and axial elongation rate (annual rate of change in AL from t-1 to t), controlling for a pre-defined set of covariates including sex, age, central corneal thickness, anterior chamber depth and lens thickness (at t-1). LMM was also used to assess the contemporaneous association between IOP and axial length (AL) at t, controlling for the same set of covariates (at t) as before., Results: Higher IOP was associated with slower axial growth (β = -0.01, 95% CI -0.02 to -0.005, p = 0.001). There was a positive contemporaneous association between IOP and AL (β = 0.03, 95% CI 0.01-0.05, p = 0.004), but this association became progressively less positive with increasing age, as indicated by a negative interaction effect between IOP and age on AL (β = -0.01, 95% CI -0.01 to -0.003, p = 0.001)., Conclusions: Higher IOP is associated with slower rather than faster axial growth in children with non-pathological high myopia, an association plausibly confounded by the increased influence of ocular compliance on IOP., (© 2023. The Author(s).)

Introduction: Hyperopia is associated with reduced vision and educational outcomes in schoolchildren. This study explored the impact of clinically significant hyperopia (≥+2.00 D) on visual function in schoolchildren and compared the ability of different screening tests (alone and in combination) to detect this level of hyperopia., Methods: Vision testing including monocular logMAR visual acuity (VA) measured to threshold (distance [DVA], near [NVA] and DVA through a plus lens [+2.50 D]), stereoacuity and cycloplegic autorefraction (tropicamide 1%) were undertaken on 263 schoolchildren (mean age: 11.76 years ± 3.38) in Queensland, Australia. Vision measures were compared between children with clinically significant hyperopia in at least one meridian (≥+2.00 D) and emmetropia/low hyperopia (>0.00 and <+2.00 D). Receiver operating curve (ROC) analysis was performed to identify optimal pass/fail criteria for each test and the diagnostic accuracy of individual and combinations of tests., Results: Thirty-two children had clinically significant hyperopia and 225 had emmetropia/low hyperopia. DVA and NVA were worse (p < 0.01), while the difference in DVA through a plus lens was less in children with clinically significant hyperopia (p < 0.01). ROC analysis for individual tests resulted in areas under the curve (AUCs) ranging from 0.65 to 0.85. Combining screening tests revealed that failing one or more of the following tests was most effective for detecting hyperopia: DVA, NVA and difference in DVA through a plus lens, resulting in a sensitivity and specificity of 72% and 81%, respectively., Conclusion: Significant differences in visual function existed between schoolchildren with clinically significant hyperopia and emmetropia/low hyperopia. Combining measures of DVA and NVA and the difference in DVA through a plus lens demonstrated good discriminative ability for detecting clinically significant hyperopia in this population., (© 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Background: A repository of retinal images for research is being established in Scotland. It will permit researchers to validate, tune, and refine artificial intelligence (AI) decision-support algorithms to accelerate safe deployment in Scottish optometry and beyond. Research demonstrates the potential of AI systems in optometry and ophthalmology, though they are not yet widely adopted., Objective: In this study, 18 optometrists were interviewed to (1) identify their expectations and concerns about the national image research repository and their use of AI decision support and (2) gather their suggestions for improving eye health care. The goal was to clarify attitudes among optometrists delivering primary eye care with respect to contributing their patients' images and to using AI assistance. These attitudes are less well studied in primary care contexts. Five ophthalmologists were interviewed to discover their interactions with optometrists., Methods: Between March and August 2021, 23 semistructured interviews were conducted online lasting for 30-60 minutes. Transcribed and pseudonymized recordings were analyzed using thematic analysis., Results: All optometrists supported contributing retinal images to form an extensive and long-running research repository. Our main findings are summarized as follows. Optometrists were willing to share images of their patients' eyes but expressed concern about technical difficulties, lack of standardization, and the effort involved. Those interviewed thought that sharing digital images would improve collaboration between optometrists and ophthalmologists, for example, during referral to secondary health care. Optometrists welcomed an expanded primary care role in diagnosis and management of diseases by exploiting new technologies and anticipated significant health benefits. Optometrists welcomed AI assistance but insisted that it should not reduce their role and responsibilities., Conclusions: Our investigation focusing on optometrists is novel because most similar studies on AI assistance were performed in hospital settings. Our findings are consistent with those of studies with professionals in ophthalmology and other medical disciplines: showing near universal willingness to use AI to improve health care, alongside concerns over training, costs, responsibilities, skill retention, data sharing, and disruptions to professional practices. Our study on optometrists' willingness to contribute images to a research repository introduces a new aspect; they hope that a digital image sharing infrastructure will facilitate service integration., (©Aurora Constantin, Malcolm Atkinson, Miguel Oscar Bernabeu, Fiona Buckmaster, Baljean Dhillon, Alice McTrusty, Niall Strang, Robin Williams. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 25.05.2023.)

Purpose: As the prevalence of eye diseases increases, demand for effective, accessible and equitable eye care grows worldwide. This is especially true in lower and middle-income countries, which have variable levels of infrastructure and economic resources to meet this increased demand. In the present study we aimed to review the literature on eye care in Pakistan comprehensively, with a particular focus on eye care pathways, patient priorities and economics., Methods: A systematic scoping review was performed to identify literature relating to eye care in Pakistan. Searches of relevant electronic databases and grey literature were carried out. The results were analysed through a mixed methods approach encompassing descriptive numerical summary and thematic analysis. To consolidate results and define priority areas for future study, expert consultation exercises with key stakeholders were conducted using qualitative semi-structured interviews., Results: One hundred and thirty-two papers (published and unpublished) were included in the final review. The majority (n = 93) of studies utilised a quantitative design. Seven interlinked themes were identified: eye care pathways, burden of eye disease, public views on eye-related issues, workforce, barriers to uptake of eye care services, quality of eye care services and economic impact of blindness. Research priorities included investigating the eye care workforce, the quality and efficiency of current eye care services, eye care services available in rural Pakistan and the costs and benefits related to eye care provision and sustaining eye care programmes., Conclusions: To the best of our knowledge, this is the first review to synthesise evidence from papers across the field relating to eye care in Pakistan. As such, this work provides new insights into the achievements of the national eye health programme, challenges in eye care in Pakistan and priority areas for future research., (© 2022 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Ethnopharmacological Relevance: Age-related macular degeneration (AMD) is a chronic neurodegenerative disease which causes irreversible central vision loss among the elderly population. Traditional Chinese Medicine (TCM), including formulas, acupuncture and herbs, has been used in the treatment of AMD for thousands of years and is currently used by many AMD patients around the world., Aim of the Review: A comprehensive, in-depth literature review examining the use of TCM in the treatment of AMD has yet to be compiled. This review will improve current knowledge relating to the use of TCM and will open new avenues of exploration in developing new drugs for the treatment of AMD., Methods: A literature search of the PubMed database, Web of Science, Google Scholar and China National Knowledge Infrastructure (CNKI) was performed using relevant terms and keywords related to TCM in the treatment of AMD. Related books, PhD and master's theses were also researched., Results: The TCM-based interpretation of AMD has been used to establish a theoretical foundation for understanding the effect of TCM formulas and acupuncture on AMD. The possible mechanism of action of common Chinese herbs has also been discussed in detail., Conclusion: TCM is a promising treatment option of AMD patients. However, lack of rigorous scientific evidence has limited the impact and uptake of TCM therapy. Future research should focus on improving understanding of the mechanism of action and bioactive components of TCM therapies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Retinal diseases are a leading cause of visual loss and blindness, affecting a significant proportion of the population worldwide and having a detrimental impact on quality of life, with consequent economic burden. The retina is highly metabolically active, and a number of retinal diseases are associated with metabolic dysfunction. To better understand the pathogenesis underlying such retinopathies, new technology has been developed to elucidate the mechanism behind retinal diseases. Metabolomics is a relatively new "omics" technology, which has developed subsequent to genomics, transcriptomics, and proteomics. This new technology can provide qualitative and quantitative information about low-molecular-weight metabolites (M.W. < 1500 Da) in a given biological system, which shed light on the physiological or pathological state of a cell or tissue sample at a particular time point. In this article we provide an extensive review of the application of metabolomics to retinal diseases, with focus on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), glaucoma, and retinitis pigmentosa (RP).

Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol-producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol-producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol-associated pathophysiology will help in the development of effective retinal degeneration therapies. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Retinitis pigmentosa (RP) is a group of visual disorders caused by mutations in over 70 genes. RP is characterized by initial degeneration of rod cells and late cone cell death, regardless of genetic abnormality. Rod cells are the main consumers of oxygen in the retina, and after the death of rod cells, the cone cells have to endure high levels of oxygen, which in turn leads to oxidative damage and cone degeneration. Gypenosides (Gyp) are major dammarane-type saponins of Gynostemma pentaphyllum that are known to reduce oxidative stress and inflammation. In this project we assessed the protective effect of Gyp against cone cell death in the rpgrip1 mutant zebrafish, which recapitulate the classical pathological features found in RP patients. Rpgrip1 mutant zebrafish were treated with Gyp (50 µg/g body weight) from two-months post fertilization (mpf) until 6 mpf. Gyp treatment resulted in a significant decrease in cone cell death compared to that of untreated mutant zebrafish. A markedly low level of reactive oxygen species and increased expression of antioxidant genes were detected in Gyp-incubated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Similarly, the activities of catalase and superoxide dismutase and the level of glutathione were significantly increased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Gyp treatment also decreased endoplasmic reticulum stress in rpgrip1 mutant eyes. Expression of proinflammatory cytokines was also significantly decreased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Network pharmacology analysis demonstrated that the promotion of cone cell survival by Gyp is possibly mediated by multiple hub genes and associated signalling pathways. These data suggest treatment with Gyp will benefit RP patients.

Introduction: Since 2010, General Ophthalmic Services (GOS) legislation and Independent Prescribing (IP) enable community optometrists to manage primary eye conditions. No studies have assessed the effect of IP. We wished to determine the distribution of IP optometrists and associated hospital referral rates across Scotland., Methods: In 2019, FOI requests (General Optical Council and NHS Education Scotland) identified all registered IP optometrists in Scotland and their registered postcodes. Data regarding community eye examinations and referrals to HES since 2010 were gathered via Information Services Division of NHS Scotland., Results: As of March 2019, there were 278 IP optometrists in Scotland (278/1189; 23.4%). Two hundred eighteen IP optometrists work in 293 practices across 11 of Scotland's 14 health boards. There was a strong correlation (r = +0.96) between population density and number of IP optometrists. Fifty-six percent of IP optometrists work in the two most deprived quintiles. Since IP's introduction, there has been a marked increase in anterior segment supplementary visits (+290%). Optometry referrals to GPs have reduced by 10.5%, but referrals to HES have increased by 118% (to 96,315). There was no correlation between quantity of IP optometrists and referral rates to HES (r = -0.06, 95% CI -0.64 to 0.56, p = 0.86)., Conclusions: This is the first analysis of IP optometrists and associated referral rates in Scotland. Despite good geographical distribution and increased supplementary attendances, optometric referrals to HES have doubled and continue to rise. We propose a ratio of primary, supplementary, non-referral and referral rates to discern the true impact of IP versus non-IP community optometric behaviour.

Background/aims: To report the protocol of a trial designed to evaluate the efficacy, safety and mechanism of action of low-dose atropine (0.01%) eye-drops for reducing progression of myopia in UK children., Methods: Multicentre, double-masked, superiority, placebo-controlled, randomised trial. We will enrol children aged 6-12 years with myopia of -0.50 dioptres or worse in both eyes.We will recruit 289 participants with an allocation ratio of 2:1 (193 atropine; 96 placebo) from five centres. Participants will instil one drop in each eye every day for 2 years and attend a research centre every 6 months. The vehicle and preservative will be the same in both study arms.The primary outcome is SER of both eyes measured by autorefractor under cycloplegia at 2 years (adjusted for baseline). Secondary outcomes include axial length, best corrected distance visual acuity, near visual acuity, reading speed, pupil diameter, accommodation, adverse event rates and allergic reactions, quality of life (EQ-5D-Y) and tolerability at 2 years. Mechanistic evaluations will include: peripheral axial length, peripheral retinal defocus, anterior chamber depth, iris colour, height and weight, activities questionnaire, ciliary body biometry and chorioretinal thickness. Endpoints from both eyes will be pooled in combined analysis using generalised estimating equations to allow for the correlation between eyes within participant. Three years after cessation of treatment, we will also evaluate refractive error and adverse events., Conclusions: The Childhood Atropine for Myopia Progression in the UK study will be the first randomised trial reporting outcomes of low-dose atropine eye-drops for children with myopia in a UK population., Trial Registration Number: ISRCTN99883695, NCT03690089., Competing Interests: Competing interests: NL: research funding from CooperVision, Essilor and Zeiss., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Near work, accommodative inaccuracy and ambient lighting conditions have all been implicated in the development of myopia. However, differences in accommodative responses with age and refractive error under different visual conditions remain unclear. This study explores differences in accommodative ability and refractive error with exposure to differing ambient illumination and visual demands in Malay schoolchildren and adults., Methods: Sixty young adults (21-25 years) and 60 schoolchildren (8-12 years) were recruited. Accommodative lag and accommodative fluctuations at far (6 m) and near (25 cm) were measured using the Grand Seiko WAM-5500 open-field autorefractor. The effects of mesopic room illumination on accommodation were also investigated., Results: Repeated-measures ANOVA indicated that accommodative lag at far and near differed significantly between schoolchildren and young adults [F(1.219, 35.354) = 11.857, p < 0.05]. Post hoc tests using the Bonferroni correction showed that at near, there was a greater lag in schoolchildren (0.486 ± 0.181 D) than young adults (0.259 ± 0.209 D, p < 0.05). Repeated-measures ANOVA also revealed that accommodative lag at near demands differed statistically between the non-myopic and myopic groups in young adults and schoolchildren [F(3.107, 31.431) = 12.187, p < 0.05]. Post hoc tests with Bonferroni correction showed that accommodative lag at near was significantly greater in myopic schoolchildren (0.655 ± 0.198 D) than in non-myopic schoolchildren (0.202 ± 0.141 D, p < 0.05) and myopic young adults (0.316 ± 0.172 D, p < 0.05), but no significant difference was found between myopic young adults (0.316 ± 0.172 D) and non-myopic young adults (0.242 ± 0.126 D, p > 0.05). Accommodative lag and fluctuations were greater under mesopic room conditions for all ages [all p < 0.05]., Conclusion: Greater accommodative lag was found in myopes than in emmetropes, in schoolchildren than in adults, and under mesopic conditions than under photopic conditions. Accommodative fluctuations were greatest in myopes and in mesopic conditions. These results suggest that differences exist in the amount of blur experienced by myopes and non-myopes at different ages and under different lighting conditions.

Purpose: The Myopia Outcome Study of Atropine in Children (MOSAIC) is an investigator-led, double-masked, randomized controlled trial investigating the efficacy and safety of 0.01% atropine eye drops for managing myopia progression in a predominantly White, European population., Methods: Children aged 6-16 years with myopia were randomly allocated 2:1 to nightly 0.01% atropine or placebo eye drops in both eyes for 2 years. The primary outcome was cycloplegic spherical equivalent (SE) progression at 24 months. Secondary outcomes included axial length (AL) change, safety and acceptability. Linear mixed models with random intercepts were used for statistical analyses., Results: Of 250 participants enrolled, 204 (81.6%) completed the 24-month visit (136 (81.4%) treatment, 68 (81.9%) placebo). Baseline characteristics, drop-out and adverse event rates were similar between treatment and control groups. At 24 months, SE change was not significantly different between 0.01% atropine and placebo groups (effect = 0.10 D, p = 0.07), but AL growth was lower in the 0.01% atropine group, compared to the placebo group (-0.07 mm, p = 0.007). Significant treatment effects on SE (0.14 D, p = 0.049) and AL (-0.11 mm, p = 0.002) were observed in children of White, but not non-White (SE = 0.05 D, p = 0.89; AL = 0.008 mm, p = 0.93), ethnicity at 24 months. A larger treatment effect was observed in subjects least affected by COVID-19 restrictions (SE difference = 0.37 D, p = 0.005; AL difference = -0.17 mm, p = 0.001)., Conclusions: Atropine 0.01% was safe, well-tolerated and effective in slowing axial elongation in this European population. Treatment efficacy varied by ethnicity and eye colour, and potentially by degree of COVID-19 public health restriction exposure during trial participation., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Prior research suggests that increased adolescent risk-taking in the presence of peers may be linked to the influence of peers on the valuation and processing of rewards during decision-making. The current study explores this idea by examining how peer observation impacts the processing of rewards when such processing is isolated from other facets of risky decision-making (e.g. risk-perception and preference, inhibitory processing, etc.). In an fMRI paradigm, a sample of adolescents (ages 14-19) and adults (ages 25-35) completed a modified High/Low Card Guessing Task that included rewarded and un-rewarded trials. Social context was manipulated by having participants complete the task both alone and while being observed by two, same-age, same-sex peers. Results indicated an interaction of age and social context on the activation of reward circuitry during the receipt of reward; when observed by peers adolescents exhibited greater ventral striatal activation than adults, but no age-related differences were evinced when the task was completed alone. These findings suggest that, during adolescence, peers influence recruitment of reward-related regions even when they are engaged outside of the context of risk-taking. Implications for engagement in prosocial, as well as risky, behaviors during adolescence are discussed., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Age-related macular degeneration (AMD) is a complex eye disorder with an environmental and genetic origin, affecting millions worldwide. The study aims to explore the association between retinal morphology and the polygenic risk score (PRS) for AMD using fundus images and deep learning techniques. Methods: The study used and pre-processed 23,654 fundus images from 332 subjects (235 patients with AMD and 97 controls), ultimately selecting 558 high-quality images for analysis. The fine-tuned DenseNet121 deep learning model was employed to estimate PRS from single fundus images. After training, deep features were extracted, fused, and used in machine learning regression models to estimate PRS for each subject. The Grad-CAM technique was applied to examine the relationship between areas of increased model activity and the retina's morphological features specific to AMD. Results: Using the hybrid approach improved the results obtained by DenseNet121 in 5-fold cross-validation. The final evaluation metrics for all predictions from the best model from each fold are MAE = 0.74, MSE = 0.85, RMSE = 0.92, R2 = 0.18, MAPE = 2.41. Grad-CAM heatmap evaluation showed that the model decisions rely on lesion area, focusing mostly on the presence of drusen. The proposed approach was also shown to be sensitive to artifacts present in the image. Conclusions: The findings indicate an association between fundus images and AMD PRS, suggesting that deep learning models may effectively estimate genetic risk for AMD from retinal images, potentially aiding in early detection and personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Glaucoma is a widespread ophthalmological disease, with a high impact and frequent visual morbidity. While the physiopathology of the two types of primary glaucoma (open angle and angle closure) has been studied, there seems to be little relationship between the two. In this study, we gather clinical and preclinical data to support the idea that the two primary glaucomas are "mirrored" in terms of morphological parameters and disease physiopathology. In short, primary angle closure glaucoma (PACG) is associated with hyperopia and low axial length, and primary open angle glaucoma (POAG) is associated with myopia and high axial length. Moreover, in PACG and in primary angle closure or primary angle closure suspect cases, while there is extensive iridotrabecular contact, the intraocular pressure (IOP) is still maintained in the lower half of the normal range throughout the evolution of the disease, which suggests a baseline trabecular hyperfiltration in PACG. In the opposite case, myopic eyes with open angles and a higher risk of developing POAG often have a baseline IOP in the upper half of the normal range, suggesting a baseline trabecular hypofiltration. As we explore clinical, genetic and animal model data regarding these opposing aspects, we hypothesize the existence of a mirroring relationship between PACG and POAG. Defining the relationship between the two potentially blinding diseases, with a high prevalence worldwide, may aid in understanding the mechanisms better and refining diagnosis and treatment. Thus, our theory has been named the Mirror Theory of Primary Glaucomas. [ABSTRACT FROM AUTHOR]

Limitation of the action of the medial rectus muscle will cause limitation of adduction of the eye just as limitation of the lateral rectus will cause limitation of abduction. factors limiting the action of the medial rectus are: (i) loss of ability of the muscle to contract beyond a certain proportion of its length; (ii) limitation of relaxation of the antagonist lateral rectus and fascia/ connections; (iii) innervational factors seen most obviously m Duane's syndrome, but also possibly active with various vertical anomalies; and (iv) loss of mechanical advantage or torque as the eye rotates inward. Using A scan the last factor may be assessed for a particular eye. There will be no loss of torque until the muscle passes a tangential point where its line of action is tangential to the globe, but torque will then be lost progressively until it becomes negligible as the null point is approached. At the null point the muscle has no torque, being perpendicular to the globe, and it marks the point where the oculomotor axis joining the centre of rotation of the eye and the apex of the orbit intersects the globe. The first three factors may be assessed clinically by measuring the adduction of the eye in degrees, and for 50 normal patients (100 eyes) the mean was 44°, standard deviation 3°. The tangential point for an average eye lies 54° behind the medial rectus muscle so for normal adduction there is no loss of torque in full adduction. The loss of torque for small recessions of the medial rectus is negligible, but for very large recessions it will be about 50% in full adduction and this is accompanied by a loss of gearing as the amount of contraction of the muscle to produce a similar rotation becomes less. Similar factors affect the action of the lateral rectus muscle, but underaction is less common probably due to the greater wrap-around effect, stressing the importance of these geometric factors. [ABSTRACT FROM AUTHOR]

Despite the significant advancements facilitated by previous research in introducing a plethora of retinal biomarkers, there is a lack of research addressing the clinical need for quantifying different biomarkers and prioritizing their importance for guiding clinical decision making in the context of retinal diseases. To address this issue, our study introduces a novel framework for quantifying biomarkers derived from optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images in retinal diseases. We extract 452 feature parameters from five feature types, including local binary patterns (LBP) features of OCT and OCTA, capillary and large vessel features, and the foveal avascular zone (FAZ) feature. Leveraging this extensive feature set, we construct a classification model using a statistically relevant p value for feature selection to predict retinal diseases. We obtain a high accuracy of 0.912 and F1-score of 0.906 in the task of disease classification using this framework. We find that OCT and OCTA's LBP features provide a significant contribution of 77.12% to the significance of biomarkers in predicting retinal diseases, suggesting their potential as latent indicators for clinical diagnosis. This study employs a quantitative analysis framework to identify potential biomarkers for retinal diseases in OCT and OCTA images. Our findings suggest that LBP parameters, skewness and kurtosis values of capillary, the maximum, mean, median, and standard deviation of large vessel, as well as the eccentricity, compactness, flatness, and anisotropy index of FAZ, may serve as significant indicators of retinal conditions. [ABSTRACT FROM AUTHOR]

Purpose: We aim to conduct a comprehensive review of outpatients at a tertiary ophthalmology clinic to evaluate various aspects including the spectrum of eye disorders, referral patterns, reasons for referral, and patient selfassessment, with a particular focus on self-referrals. Study Design: A cross-sectional study. Place and Duration of Study: Ibn Al-Haitham Teaching Eye Hospital from April to May, 2023. Methods: Referral letters were grouped into the primary health center (PHC), secondary hospital, internal referral and private clinic. Referral letter quality was assessed based on clinical information and particular request. Results: A total of 1367 individuals aged 40.8 ± 22.17 years were eligible for study. There were 19.2% referrals form PHC, 18.4% from secondary hospitals, 10.7% from private clinics, 3.3% were internal referrals, 37.2% were self-referred and 11.3% had medical or surgical follow-up. Blurred vision was the predominant complaint of 677 (51.6%) patients. Out of 659 referral letters, 25% scored two essential information items, 5.2% scored three, and only 0.8% scored four items. The majority (97.2%) of letters provided specific requests. Among all, 26.3% of PHC, 38.2% of hospitals, 34.9% of private clinics, 21.7% self-referred and 51.1% of internally referred patients considered their situations difficult. Conclusion: Majority of cases seen in ophthalmology tertiary centers consist of common conditions that could be effectively managed by PHCs and general hospitals. Improved referral standards for specialized medical institutions may reduce burden on tertiary hospitals. [ABSTRACT FROM AUTHOR]

Introduction: Our recent research has demonstrated that social comparison orientation of ability (SCO-ability) is an antecedent of trait competitiveness (TC), and TC mediates the relation between SCO-ability and domain-specific risktaking. TC is a multi-dimensional trait, therefore we sought to expand on prior research by examining whether SCO-ability predicted two distinct dimensions of TC: hypercompetitive orientation (HCO) and self-development competitive orientation (SDCO). Methods: We investigated how these different dimensions of TC mediated the relation between SCO-ability and both overall and domain-specific risk-taking in two correlational studies of 622 college students (313 males, mean age = 22.10, SD = 2.35) and 717 adult workers (368 males, mean age = 27.92, SD = 5.11). Results: We found that SCO-ability positively predicted HCO. Together, SCOability and HCO predicted overall risk-taking and risk-taking in the recreational and ethical domains in both samples. HCO mediated the relation between SCOability and both overall risk-taking and risk-taking in the recreational and ethical domains. Additionally, SCO-ability positively predicted SDCO. SCO-ability and SDCO mainly predicted risk-taking in the recreational domain in both studies. SDCO mediated the relation between SCO-ability and risk-taking only in the recreational domain. Discussion: Collectively, the findings above advance our understanding of the relation between competition and risk-taking by using differentiated measures of TC (HCO and SDCO). Our findings suggest that HCO is more strongly related to risk-taking than SDCO, thereby refining the possible role of SCO-ability and TC in predicting overall risk-taking and domain-specific risk-taking. [ABSTRACT FROM AUTHOR]