MNK2 deficiency potentiates ß-cell regeneration via translational regulation.

Regenerating pancreatic ß-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of ß-cell regeneration, but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetically validated in vivo. CID661578 increased ß-cell neogenesis from ductal cells in zebrafish, neonatal pig islet aggregates and human pancreatic ductal organoids. Mechanistically, we found that CID661578 boosts protein synthesis and regeneration by blocking MNK2 from binding eIF4G in the translation initiation complex at the mRNA cap. Unexpectedly, this blocking activity augmented eIF4E phosphorylation depending on MNK1 and bolstered the interaction between eIF4E and eIF4G, which is necessary for both hypertranslation and ß-cell regeneration. Taken together, our findings demonstrate a targetable role of MNK2-controlled translation in ß-cell regeneration, a role that warrants further investigation in diabetes.

Exploring the impact of optical corrections on visual functions in myopia control-a scoping review.

PURPOSE: Myopia is controlled optically with peripheral defocus spectacles, multifocal contact lenses, or orthokeratology lenses. However, it is unknown which optical correction will improve visual performance. This scoping review aimed to identify and summarize studies on various visual functions using optical corrections for myopia control. METHODS: To develop the search strategy, population (Myopia), concept (visual performance), and context (unrestricted race/region) were used. PubMed, SCOPUS, Cochrane Library, and Web of Science databases were searched using the keywords myopia, contrast sensitivity, high and low contrast visual acuity, stereopsis, and optical correction of myopia control. This scoping review protocol was registered in the Open Science Framework registry and followed the framework for scoping review outlined by the Joanna Briggs Institute. RESULTS: Eight studies (n = 8) met the inclusion criteria and were included in the review. Four were conducted in Europe, two were conducted in China, and one was conducted in Japan and Singapore. Five studies were randomized controlled trials, out of which three used contact lenses and two studies used peripheral defocus spectacles lenses. Studies ranged from one day to 2 years. Three studies that used orthokeratology lenses were prospective study designs. Among the studies that used orthokeratology lenses and contact lenses, two studies measured the contrast sensitivity function with CSV1000 (Vector Vision) under mesopic and photopic conditions, with and without glare. Two studies measured the central and peripheral contrast sensitivity using psychophysics experiments. High and low contrast visual acuity was measured using the Freiburg Vision Test (n = 1) and ETDRS charts (n = 3), and stereopsis was assessed using a random dot stereogram (n = 1). The studies showed a reduction in central and peripheral contrast sensitivity function and low contrast acuity when treated with multifocal contact lenses, orthokeratology lenses, and peripheral defocus lenses compared with single-vision lenses. CONCLUSION: This scoping review found a reduction in central and peripheral contrast sensitivity function, as well as low contrast visual acuity when using various optical corrections for myopia control, while high-contrast visual acuity remained the same. The impact of visual functions may not influence the effectiveness of myopia control. Eye care practitioners should provide awareness to the parent and patient population about the potential visual impact of recent designs for optical corrections of myopia control.

Comparison of central corneal thickness measurements by ultrasound pachymetry and 2 new devices, Tonoref III and RS-3000.

PURPOSE: There is currently little evidence assessing the repeatability and accuracy of central corneal thickness measurements using the devices Tonoref III and RS-3000. This study aims to compare these devices against measurements by ultrasound pachymetry. METHODS: Central corneal thicknesses were measured on 50 eyes. Measurements from two non-contact devices-Tonoref III (NIDEK CO., LTD, Gamagori, Japan) and RS-3000 (NIDEK CO., LTD, Gamagori, Japan)-were compared against ultrasound pachymetry, the gold standard. Ultrasound measurements were obtained using a 'Pachmate' device (DGH Technology, Inc, Exton, PA, USA). Repeatability was defined as the value that the difference between two consecutive measurements falls below 95% of the time. The within-subject standard deviation and repeatability values were calculated for Pachmate and Tonoref III by one-way ANOVA. Repeatability of RS-3000 was determined by nonparametric analysis. Agreement between Tonoref III and Pachmate was assessed by a Bland-Altman plot. Agreement between RS-3000 and Pachmate was assessed by nonparametric analysis. RESULTS: The Pachmate, Tonoref III and RS-3000 had repeatability values of 16, 7.4 and 5 µm, respectively. The mean difference between Tonoref III and Pachmate was - 15 µm (95% LoAs - 31 to + 0 µm). The median value for the difference between RS-3000 and Pachmate was - 4 µm (95% of values within - 24 and + 4 µm). CONCLUSION: The Tonoref III and RS-3000 showed good repeatability when compared to ultrasound pachymetry. However, neither instrument agreed interchangeably with CCT measurements by ultrasound pachymetry. Practitioners should determine whether the level of agreement is sufficient to meet their clinical needs.

A Possible Association Between Dry Eye Symptoms and Body Fat: A Prospective, Cross-Sectional Preliminary Study.

OBJECTIVES: To examine the relationship between dry eye symptoms and adiposity in a population study. METHODS: A prospective cross-sectional single-visit preliminary study was designed to sample ocular symptoms and indices of adiposity in the general adult population. Patients recruited from the UNSW optometry clinic, the university campus and surrounding community, and overseas were invited to complete a survey composed of the short form Dry Eye Questionnaire (SFDEQ) (Dry Eye Questionnaire-5 or Contact Lens Dry Eye Questionnaire-8) and the Ocular Comfort Index (OCI) via hardcopy or online. Participants self-measured their weight, height, waist circumference (WC), and body fat % (optional). Associations between measures of adiposity (Body mass index [BMI], WC, and body fat %) and ocular symptoms scores (SFDEQ and OCI) were determined using Spearman correlation coefficients. Group differences were compared using independent t test. RESULTS: Three hundred and five participants including 52 contact lens wearers completed the study and 78 of them measured body fat %. There was a moderate correlation between body fat % and dry eye symptoms (SFDEQ r=0.34, P=0.003; OCI r=0.32, P=0.004). The interaction between body fat % and gender, wear of contact lenses, and older age were shown to be significant predictors of less ocular comfort in multivariate analysis (F(3,74)=12.13, P<0.001). CONCLUSIONS: An association between adiposity measured by body fat % and symptoms of dry eye was demonstrated in the general adult population. Confirmation of these findings in a large study is required.

Myopia control during orthokeratology lens wear in children using a novel study design.

PURPOSE: To investigate the effect of overnight orthokeratology (OK) contact lens wear on axial length growth in East Asian children with progressive myopia. DESIGN: A prospective, randomized, contralateral-eye crossover study conducted over a 1-year period. PARTICIPANTS: We enrolled 26 myopic children (age range, 10.8-17.0 years) of East Asian ethnicity. METHODS: Subjects were fitted with overnight OK in 1 eye, chosen at random, and conventional rigid gas-permeable (GP) lenses for daytime wear in the contralateral eye. Lenses were worn for 6 months. After a 2-week recovery period without lens wear, lens-eye combinations were reversed and lens wear was continued for a further 6 months, followed by another 2-week recovery period without lens wear. Axial eye length was monitored at baseline and every 3 months using an IOLMaster biometer. Corneal topography (Medmont E300) and objective refraction (Shin-Nippon NVision-K 5001 autorefractor) were also measured to confirm that OK lens wear was efficacious in correcting myopia. MAIN OUTCOME MEASUREMENTS: Axial length elongation and myopia progression with OK were compared with conventional daytime rigid contact lens wear. RESULTS: After 6 months of lens wear, axial length had increased by 0.04±0.06 mm (mean±standard deviation) in the GP eye (P=0.011) but showed no change (-0.02±0.05 mm) in the OK eye (P=0.888). During the second 6-month phase of lens wear, in the OK eye there was no change from baseline in axial length at 12 months (-0.04±0.08 mm; P=0.218). However, in the GP eye, the 12-month increase in axial length was significant (0.09±0.09 mm; P<0.001). The GP lens-wearing eye showed progressive axial length growth throughout the study. CONCLUSIONS: These results provide evidence that, at least in the initial months of lens wear, overnight OK inhibits axial eye growth and myopia progression compared with conventional GP lenses. Apparent shortening of axial length early in OK lens wear may reflect the contribution of OK-induced central corneal thinning, combined with choroidal thickening or recovery due to a reduction or neutralization of the myopiogenic stimulus to eye growth in these myopic children.

The Effects of Vertical Yoked Prism on Horizontal Heterophoria.

PURPOSE: Vertical yoked prisms (VYPs) have been recommended for the remediation of vergence dysfunction, but the evidence base for their use is mostly low level. This study investigates the effect of VYP on horizontal subjective dissociated heterophoria. METHODS: Phoria measurement was performed in primary gaze with the Modified Thorington technique at 3 m and at 40 cm on 40 nonpresbyopic young adults. Subjects were seated and head position was held constant. Baseline measures (without yoked prism) of distance and near phoria were measured. Phorias were measured again through the following range of VYP, randomly presented: 2 prism diopters (Δ) base up (BU), 2Δ base down (BD), 5Δ BU, and 5Δ BD. Twenty-six subjects also had their phorias measured with control lenses of +0.125 DS OU (because of unavailability of Plano trial lenses) randomly presented along the other conditions. RESULTS: There was no significant difference overall between phoria measured in any of the yoked prism conditions, including the baseline measure, at distance or near. Neither was there evidence of a predictable esophoric or exophoric shift with either BU or BD prism. CONCLUSIONS: Vertical yoked prisms did not exert any immediate effect on horizontal phoria in young adults when posture was controlled. This suggests that, if VYPs do indeed improve horizontal vergence problems, they do not do so by a direct or immediate impact on horizontal phoria.

Attitudes and barriers to evidence-based practice in optometry educators.

PURPOSE: Evidence-based practice (EBP) is an essential component of good quality, patient-centered health care. This requires practitioners to acquire EBP skills and knowledge during undergraduate and continuing education. Evidence-based practice education exists in a range of health care disciplines, including optometry. Evidence-based practice education, however, depends on relevant skills and knowledge in educators. Courses and workshops exist for the development of EBP teaching skills in some areas of health care but not in optometry. Here, we describe a pilot workshop designed to enhance the teaching of EBP and to investigate the perspectives of optometric educators on EBP including their attitudes and perceived barriers to EBP and its teaching. METHODS: Twenty-seven optometric educators including 8 facilitators participated. Of these, 14 were academics (including the 8 facilitators) and 13 were practitioners. Evidence-based practice attitudes were assessed using the Evidence-Based Practice Attitude Scale-50 with appropriate modifications for optometry. Workshop design incorporated strategies to trigger discussion among participants. A nominal group technique was used to identify, prioritize, and reach consensus on barriers to EBP. RESULTS: Although some participants expressed reservations about EBP, a common understanding of the contemporary definition of EBP emerged in educators. Thirty-five barriers to EBP were identified; "time" was selected in the top five barriers by most participants and attracted the highest total score, well above any other barrier (negative attitude to EBP, volume of evidence, integration with clinical practice, and lack of lifelong learning mind-set). Attitudes toward EBP were generally positive and negatively correlated with age and time since graduation, respectively. CONCLUSIONS: A group of optometrists and academics new to implementing education in EBP displayed positive attitudes to EBP but considered that its application and teaching could be significantly hindered by a lack of time to access and appraise the large volume of available research evidence in the field of eye care.

Toca-1 is suppressed by p53 to limit breast cancer cell invasion and tumor metastasis.

INTRODUCTION: Transducer of Cdc42-dependent actin assembly-1 (Toca-1) recruits actin regulatory proteins to invadopodia, and promotes breast tumor metastasis. Since metastatic breast tumors frequently harbor mutations in the tumor suppressor p53, we tested whether p53 regulates Toca-1 expression. METHODS: Normal mammary epithelial cells (HBL-100, MCF10A) and breast cancer cell lines expressing wild-type (WT) p53 (DU4475, MTLn3) were treated with camptothecin or Nutlin-3 to stabilize p53 to test effects on Toca-1 mRNA and protein levels. Chromatin immunoprecipitation (ChIP) assays were performed to identify p53 binding site in Toca-1 gene. Stable silencing of p53 and Toca-1 were performed in MTLn3 cells to test effects on invadopodia and cell invasion in vitro, and tumor metastasis in vivo. RESULTS: We observed that breast cancer cell lines with mutant p53 have high levels of Toca-1 compared to those with WT p53. Stabilization of WT p53 led to further reduction in Toca-1 mRNA and protein levels in normal breast epithelial cells and breast cancer cells. ChIP assays revealed p53 binding within intron 2 of toca1, and reduced histone acetylation within its promoter region upon p53 upregulation or activation. Stable silencing of WT p53 in MTLn3 cells led to increased extracellular matrix degradation and cell invasion compared to control cells. Interestingly, the combined silencing of p53 and Toca-1 led to a partial rescue of these effects of p53 silencing in vitro and reduced lung metastases in mice. In human breast tumors, Toca-1 levels were high in subtypes with frequent p53 mutations, and high Toca-1 transcript levels correlated with increased risk of relapse. CONCLUSIONS: Based on these findings, we conclude that loss of p53 tumor suppressor function in breast cancers leads to upregulation of Toca-1, and results in enhanced risk of developing metastatic disease.

Impact of age on measurement variability for axial length in myopic children.

CLINICAL RELEVANCE: Axial length is a primary outcome in the management of progressive myopia. However, young children may have difficulty fixating during these measurements compared to older children, which can result in higher measurement variability. This may affect perceived axial length progression, leading to inappropriate management. BACKGROUND: This study assessed the impact of patient age on measurement variability for axial length measurements taken with the IOLMaster 700 and IOLMaster 500 in myopic children. METHODS: A retrospective review of records was undertaken at a university optometry clinic. Five axial length measurements captured at the same visit were collected with the IOLMaster 700 and IOLMaster 500 for myopic patients ≤16 years. The within-subject standard deviation and R2 were calculated for each instrument to examine the effects of age on instrument variability. RESULTS: Data was collected for 51 patients (30 female and 21 male), and the mean age was 10.98 ± 2.77 years. Mean axial length measured with the IOLMaster 700 was longer compared to the IOLMaster 500 (difference -0.02 ± 0.02 mm; p < 0.001). There was no effect of age on within-person variability for the measurement of axial lengths with either instrument, with R2 values of 0.021 (p = 0.305) and 0.13 (p = 0.420) for the IOLMaster 700 and IOLMaster 500, respectively. The within-subject variability of axial measurements with the IOLMaster 700 was significantly lower than that with the IOLMaster 500 (p < 0.001). CONCLUSION: Measurement variability of axial length measurements with the IOLMaster 700 and IOLMaster 500 was not dependent on age. However, axial length measurements captured with the IOLMaster 700 were significantly longer and less variable than those with the IOLMaster 500. Eye health care practitioners should be aware of the differences between the two instruments and refrain from using them interchangeably, especially for myopia control where small changes in axial length can affect patient management.

Predicting the child who will become myopic - can we prevent onset?

Myopia has become a global epidemic with significant public health impacts. Identifying the child at risk of developing myopia, i.e. the pre-myopic child and implementing strategies to prevent the onset of myopia, could significantly reduce the burden of myopia on an individual and society. This paper is a review of publications that have identified ocular characteristics of children at risk of future myopia development including a lower than age normal amount of hyperopia and accelerated axial length elongation. Risk factors associated with increased risk of myopia development such as education exposure and reduced outdoor time, and strategies that could be implemented to prevent myopia onset in children are also explored. The strong causal role of education and outdoor time on myopia development suggests that lifestyle modifications could be implemented as preventative measures to at-risk children and may significantly impact the myopia epidemic by preventing or delaying myopia onset and its associated ocular health consequences.

Significant myopic shift over time: Sixteen-year trends in overall refraction and age of myopia onset among Chinese children, with a focus on ages 4-6 years.

Background: Myopia or near-sightedness is a major cause of blindness in China and typically develops between the ages of 6-12 years. We aimed to investigate the change in refractive error and the age of myopia onset in Chinese children from 2005 to 2021. Methods: We first conducted a series of cross-sectional studies to determine the refractive states and the age of myopia onset over time, after which we analysed longitudinal data to investigate the dose-response relationship between hyperopic reserve and future risk of myopia. The analysis was based on the refraction data of children aged 4-18 years who visited the Fudan University Eye and Ear, Nose, and Throat (FUEENT) Hospital, a large tertiary hospital in Shanghai, China, for eye examinations between 2005 and 2021. We examined the prevalence of hyperopia (spherical equivalent refractive error (SERE) >0.75D), pre-myopia (-0.50D < SERE ≤ 0.75D), and myopia (SERE ≤-0.50D), the average SERE for each age group at the initial visit, the average age of myopia onset, and the safety threshold of hyperopic reserve against myopia onset. Results: We included 870 372 eligible patients aged 4-18 years who attended examination between 2005 and 2021, 567 893 (65.2%) of whom were myopic at their initial visit to FUEENT. The mean SERE decreased in most (n/N = 14/15) of the age groups over the 16 calendar years, with a mean SERE for the whole cohort decreasing from -1.01D (standard deviation (SD) = 3.46D) in 2005 to -1.30D (SD = 3.11D) in 2021. The prevalence of pre-myopia increased over the 16 years (P < 0.001), while those of myopia and hyperopia remained largely stable (both P > 0.05). We observed a significant decrease in the prevalence of hyperopia (2005: 65.4% vs 2021: 51.1%; P < 0.001) and a significant increase in the prevalence of pre-myopia (2005: 19.0% vs 2021: 26.5%; P < 0.001) and myopia (2005: 15.6% vs 2021: 22.4%; P < 0.001) in children aged 4-6 years. We found an earlier myopia onset over time, with the mean age of onset decreasing from 10.6 years in 2005 to 7.6 years in 2021 (P < 0.001). Children with a hyperopic reserve of less than 1.50D were at increased risk of developing myopia during a median follow-up of 1.3 years. Conclusions: We found an overall myopic shift in SERE in Chinese children aged 4-18 years over the past 16 years, particularly in those aged 4-6 years. The mean age of myopia onset decreased by three years over the same period. The "safety threshold" of hyperopic reserve we identified may help target the high-risk population for early prevention.

Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism.

Peroxisomes play a central role in tuning metabolic and signaling programs in a tissue- and cell-type-specific manner. However, the mechanisms by which the status of peroxisomes is communicated and integrated into cellular signaling pathways are not yet understood. Herein, we report the cellular responses to peroxisomal proteotoxic stress upon silencing the peroxisomal protease/chaperone LONP2. Depletion of LONP2 triggered the accumulation of its substrate TYSND1 protease, while the overall expression of peroxisomal proteins, as well as TYSND1-dependent ACOX1 processing appeared normal, reflecting early stages of peroxisomal proteotoxic stress. Consequently, the alteration of peroxisome size and numbers, and luminal protein import failure was coupled with induction of cell-specific cellular stress responses. Specific to COS-7 cells was a strong activation of the integrated stress response (ISR) and upregulation of ribosomal biogenesis gene expression levels. Common changes between COS-7 and U2OS cell lines included repression of the retinoic acid signaling pathway and upregulation of sphingolipids. Cholesterol accumulated in the endomembrane compartments in both cell lines, consistent with evidence that peroxisomes are required for cholesterol flux out of late endosomes. These unexpected consequences of peroxisomal stress provide an important insight into our understanding of the tissue-specific responses seen in peroxisomal disorders.

Polysome Fractionation for Transcriptome-Wide Studies of mRNA Translation.

Protein synthesis and degradation determine the relationship between mRNA and corresponding protein amounts. This relationship can change in a dynamic and selective fashion when translational efficiencies of transcript subsets are altered downstream of, for example, translation factors and/or RNA binding proteins. Notably, even transcription factors such as estrogen receptor alpha (ERα) can modulate mRNA translation in a transcript-selective manner. Yet, despite ample evidence suggesting a key role for mRNA translation in shaping the proteome in health and disease, it remains largely unexplored. Here, we present a guide for the extraction of mRNA engaged in translation using polysome fractionation with linear and optimized sucrose gradients. The isolated polysome-associated RNA is then quantified, in parallel with total mRNA from the same conditions, using methods such as RNA sequencing; and the resulting data set is analyzed to derive transcriptome-wide insights into how mRNA translation is modulated. The methods we describe are applicable to cultured cells, small numbers of FACS-isolated primary cells, and small tissue samples from biobanks or animal studies. Accordingly, this approach can be applied to study in detail how ERα and other factors control gene expression by selectively modulating mRNA translation both in vitro and in vivo.

Anota2seq Analysis for Transcriptome-Wide Studies of mRNA Translation.

mRNA translation plays a critical role in determining proteome composition. In health, regulation of mRNA translation facilitates rapid gene expression responses to intra- and extracellular signals. Moreover, dysregulated mRNA translation is a common feature in disease states, including neurological disorders and cancer. Yet, most studies of gene expression focus on analysis of mRNA levels, leaving variations in translational efficiencies largely uncharacterized. Here, we outline procedures to identify mRNA-selective alterations in translational efficiencies on a transcriptome-wide scale using the anota2seq package. Anota2seq compares expression data originating from translated mRNA to data from matched total mRNA to identify changes in translated mRNA not paralleled by corresponding changes in total mRNA (interpreted as changes in translational efficiencies impacting protein levels), congruent changes in total and translated mRNA (interpreted as changes in transcription and/or mRNA stability), and changes in total mRNA not paralleled by corresponding alterations in translated mRNA (interpreted as translational buffering). To illustrate the functionality of the anota2seq analysis package, we demonstrate a detailed analysis using a polysome-profiling data set quantified by RNA sequencing, revealing that estrogen receptor α modulates gene expression via a type of translational buffering termed offsetting. Notably, this anota2seq analysis procedure is also applicable to ribosome-profiling (RiboSeq) data sets and can be adapted to a variety of other data types and experimental contexts. Finally, we provide guidance for extending anota2seq analysis to examine associations between untranslated regions and altered translational efficiencies as well as targeted cellular functions to gain insights into mechanisms and phenotypic consequences of altered mRNA translation. Thus, this step-by-step manual allows users to interrogate selective changes in mRNA translation on a transcriptome-wide scale using the Bioconductor package anota2seq.

Povidone iodine for the treatment of adenoviral conjunctivitis.

Adenoviral conjunctivitis is the most common cause of ocular viral infection in the world, but currently has no approved therapeutic treatments. The antiseptic povidone-iodine (PVP-I) has been used as an off-label treatment for the condition, but high-quality evidence for its use is limited. This paper aims to review the literature surrounding the use of PVP-I in the management of adenoviral conjunctivitis. Unfortunately, treatment regimens, inclusion criteria, outcome measures, and review periods vary widely between studies, making direct comparisons between outcomes difficult. The majority of studies investigate daily instillation of 0.4 to 2.0% PVP-I rather than one-time instillation of PVP-I as has been used anecdotally in practice. In addition, only one treatment arm investigates daily PVP-I alone, with no significant difference in the duration of disease or clinical outcome compared to placebo. All other treatment arms investigate PVP-I in combination with dexamethasone which generally improve outcomes. Tolerability of PVP-I is generally good for low concentrations <1.0%, but efficacy of treatment is generally reported to be concentration dependent. Future research should investigate the optimal concentration, dosing regimen and role of each agent in combination treatment and aim to use laboratory techniques to improve diagnosis and provide quantifiable outcomes.

Current understanding and therapeutic management of contact lens associated sterile corneal infiltrates and microbial keratitis.

Contact lenses are widely prescribed in clinical practice with multiple applications and advantages. However, contact lenses can be associated with various complications which range from innocuous to severe. Clinicians thus not only need to possess the ability to prescribe the most appropriate contact lenses for each individual patient but also be able to recognise and manage any associated complications. This review examines the existing literature on the management of corneal infiltrative events associated with soft contact lenses, including microbial keratitis, particularly in the context of practising in Australia. The definitions and diagnosis of corneal infiltrative events, as well as the current understanding of their aetiologies, will be explored. The various aspects of a successful management will be discussed, including the applications of therapeutic agents such as antimicrobial and anti-inflammatory agents, the role of microbiological investigations, and strategies to improve long-term prognosis. The currently available evidence supporting management options will be presented, highlighting the relative abundance of high-level evidence on management protocols, antimicrobial selection and treatment duration for microbial keratitis; and the relative paucity of studies and trials for sterile corneal infiltrative events, despite this condition being much more commonly encountered in clinical practice.

Risk factors for rapid axial length elongation with low concentration atropine for myopia control.

Three hundred and twenty-eight myopic children, randomized to use either 0.01% (N = 166) or 0.02% (N = 162) atropine were enrolled in this study. Gender, age, body mass index(BMI), parental myopia status, atropine concentration used, pupil diameter, amplitude of accommodation, spherical equivalent refractive error (SER), anterior chamber depth (ACD) and axial length (AL) were collected at baseline and 1 year after using atropine. Rapid AL elongation was defined as > 0.36 mm growth per year. Univariate analyses showed that children with rapid AL elongation tend to be younger, have a smaller BMI, use of 0.01% atropine, narrow ACD, lower SER, shorter AL, smaller change in pupil diameter between 1 year and baseline (all P < 0.05). Multivariate logistic regression analyses confirmed that rapid AL elongation was associated with children that were younger at baseline (P < 0.0001), use of 0.01% atropine (P = 0.04), a shorter baseline AL (P = 0.03) and a smaller change in pupil diameter between 1 year and baseline (P = 0.04). Younger children with shorter AL at baseline, less change in their pupil diameter with atropine treatment and using the lower of the two atropine concentrations may undergo rapid AL elongation over a 12 months myopia control treatment period.

Distinguishing Tumor and Stromal Sources of MicroRNAs Linked to Metastasis in Cutaneous Melanoma.

MicroRNA (miRNA) dysregulation in cancer causes changes in gene expression programs regulating tumor progression and metastasis. Candidate metastasis suppressor miRNA are often identified by differential expression in primary tumors compared to metastases. Here, we performed comprehensive analysis of miRNA expression in The Cancer Genome Atlas (TCGA) skin cutaneous melanoma (SKCM) tumors (97 primary, 350 metastatic), and identified candidate metastasis-suppressor miRNAs. Differential expression analysis revealed miRNA significantly downregulated in metastatic tumors, including miR-205, miR-203, miR-200a-c, and miR-141. Furthermore, sequential feature selection and classification analysis identified miR-205 and miR-203 as the miRNA best able to discriminate between primary and metastatic tumors. However, cell-type enrichment analysis revealed that gene expression signatures for epithelial cells, including keratinocytes and sebocytes, were present in primary tumors and significantly correlated with expression of the candidate metastasis-suppressor miRNA. Examination of miRNA expression in cell lines revealed that candidate metastasis-suppressor miRNA identified in the SKCM tumors, were largely absent in melanoma cells or melanocytes, and highly restricted to keratinocytes and other epithelial cell types. Indeed, the differences in stromal cell composition between primary and metastatic tumor tissues is the main basis for identification of differential miRNA that were previously classified as metastasis-suppressor miRNAs. We conclude that future studies must consider tumor-intrinsic and stromal sources of miRNA in their workflow to identify bone fide metastasis-suppressor miRNA in cutaneous melanoma and other cancers.

Prevalence of myopia among disadvantaged Australian schoolchildren: A 5-year cross-sectional study.

PURPOSE: Myopia prevalence is influenced by environmental factors including heritability and social disadvantage. The current prevalence of myopia among disadvantaged school children in Australia has not been reported. Therefore, this study analyses refractive data for children from rural and outer suburban areas. METHODS: The records of 4,365 children aged 6-15 visiting a city-based government-school respite care center during the years 2014/2016/2018 were analyzed for right eye non-cycloplegic spherical equivalent refraction (SER). The prevalence of myopia (SER≤-0.50D) was compared with historical data. RESULTS: The prevalence of myopia was 3.5%, 4.4% and 4.3% in 2014, 2016 and 2018, respectively. The prevalence of myopia increased with age (P<0.0001), but was not related to sex or year of testing (all P >0.05). The overall mean SER was 0.89±0.86D, 0.62±0.89D and 0.56±0.95 in 2014, 2016 and 2018, respectively. Mean SER was associated with year of testing, age (all P <0.0001) and sex (P = 0.03). Mean SER decreased slightly from 2014 to 2018 and demonstrated a significant shift towards less hyperopia with increasing age. Mean SER of females was higher than that of males and decreased faster than in males with age (P interaction = 0.03). CONCLUSIONS: Myopia prevalence increased with age. The mean SER decreased slightly from 2014 to 2018. Sex differences in the rate of change with age was observed. Compared with 40 years ago, the prevalence of myopia has doubled, but it remains significantly lower than in school children of a similar age living in established urban areas that are regarded as having a higher socioeconomic status.

Effect of low-dose atropine on myopia progression, pupil diameter and accommodative amplitude: low-dose atropine and myopia progression.

PURPOSE: To evaluate the effects of 0.01% and 0.02% atropine eye drops on myopia progression, pupil diameter and accommodative amplitude in myopic children. METHODS: A cohort study assessed 400 myopic children divided into three groups: 138 and 142 children were randomised to use either 0.02% or 0.01% atropine eye drops, respectively. They wore single-vision (SV) spectacles, with one drop of atropine eye drop applied to both eyes once nightly. Control children (n=120) only wore SV spectacles. Repeated measurements of spherical equivalent refractive errors (SERs), axial length (AL), pupil diameter and accommodative amplitude were performed at baseline, and 4, 8 and 12 months after treatment. RESULTS: After 12 months, the SER change was -0.38±0.35D, -0.47±0.45D, -0.70±0.60D and AL change was 0.30±0.21 mm, 0.37±0.22 mm, 0.46±0.35 mm in the 0.02%, 0.01% atropine and control groups, respectively. There were significant differences in the change in AL and SER between three groups (all p<0.001). Between baseline and the 12-month visit, the overall change in accommodative amplitude was 1.50±0.25D, 1.61±0.31D and change in pupil diameter was 0.78±0.42 mm, 0.69±0.39 mm, with 0.02% and 0.01% atropine, respectively. Accommodative amplitude significantly decreased and pupil diameter significantly increased in two atropine groups (all p<0.001). Moreover, there was no statistical difference in the change difference in accommodative amplitude and pupil diameter between two atropine groups (p=0.24, p=0.38), whereas the accommodative amplitude (p=0.45) and pupil diameter (p=0.39) in the control group remained stable. CONCLUSIONS: 0.02% atropine eye drops had a better effect on myopia progression than 0.01% atropine, but 0.02% and 0.01% atropine showed similar effects on pupil diameter and accommodative amplitude after 12 months of treatment. TRIAL REGISTRATION NUMBER: ChiCTR-IPD-16008844.