Cerebral visual impairment: genetic diagnoses and phenotypic associations.

BACKGROUND: Cerebral visual impairment (CVI) is the most common form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders. METHODS: We carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100 000 Genomes Project (100KGP). RESULTS: 158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, while the remaining 148 are candidate genes for this phenotype. Gene ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggests that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI. CONCLUSION: This study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.

Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial.

Importance: The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression. Objective: To assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression. Design, Setting, and Participants: This was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with -0.50 diopter (D) to -6.00 D spherical equivalent refractive error (SER) and no worse than -1.50 D astigmatism. Interventions: Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months. Main Outcomes and Measures: The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported. Results: A total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (least squares mean [LSM] difference, 0.10 D; 95% CI, -0.02 D to 0.22 D; P = .10) but did slow mean axial elongation (LSM difference, -0.08 mm; 95% CI, -0.13 mm to -0.02 mm; P = .005); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (LSM difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P < .001), and slowed axial elongation (LSM difference, -0.13 mm; 95% CI, -0.19 mm to -0.07 mm; P < .001). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine. Conclusions and Relevance: This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression. Trial Registration: ClinicalTrials.gov Identifier: NCT03350620.

IMI-Nonpathological Human Ocular Tissue Changes With Axial Myopia.

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

IMI 2023 Digest.

Myopia is a dynamic and rapidly moving field, with ongoing research providing a better understanding of the etiology leading to novel myopia control strategies. In 2019, the International Myopia Institute (IMI) assembled and published a series of white papers across relevant topics and updated the evidence with a digest in 2021. Here, we summarize findings across key topics from the previous 2 years. Studies in animal models have continued to explore how wavelength and intensity of light influence eye growth and have examined new pharmacologic agents and scleral cross-linking as potential strategies for slowing myopia. In children, the term premyopia is gaining interest with increased attention to early implementation of myopia control. Most studies use the IMI definitions of ≤-0.5 diopters (D) for myopia and ≤-6.0 D for high myopia, although categorization and definitions for structural consequences of high myopia remain an issue. Clinical trials have demonstrated that newer spectacle lens designs incorporating multiple segments, lenslets, or diffusion optics exhibit good efficacy. Clinical considerations and factors influencing efficacy for soft multifocal contact lenses and orthokeratology are discussed. Topical atropine remains the only widely accessible pharmacologic treatment. Rebound observed with higher concentration of atropine is not evident with lower concentrations or optical interventions. Overall, myopia control treatments show little adverse effect on visual function and appear generally safe, with longer wear times and combination therapies maximizing outcomes. An emerging category of light-based therapies for children requires comprehensive safety data to enable risk versus benefit analysis. Given the success of myopia control strategies, the ethics of including a control arm in clinical trials is heavily debated. IMI recommendations for clinical trial protocols are discussed.

IMI-Management and Investigation of High Myopia in Infants and Young Children.

Purpose: The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤-6 diopters [D]) in infants and young children. Findings: High myopia is rare in pre-school children with a prevalence less than 1%. The etiology of myopia in such children is different than in older children, with a high rate of secondary myopia associated with prematurity or genetic causes. The priority following the diagnosis of high myopia in childhood is to determine whether there is an associated medical diagnosis that may be of greater overall importance to the health of the child through a clinical evaluation that targets the commonest features associated with syndromic forms of myopia. Biometric evaluation (including axial length and corneal curvature) is important to distinguishing axial myopia from refractive myopia associated with abnormal development of the anterior segment. Additional investigation includes ocular imaging, electrophysiological tests, genetic testing, and involvement of pediatricians and clinical geneticists is often warranted. Following investigation, optical correction is essential, but this may be more challenging and complex than in older children. Application of myopia control interventions in this group of children requires a case-by-case approach due to the lack of evidence of efficacy and clinical heterogeneity of high myopia in young children. Conclusions: High myopia in infants and young children is a rare condition with a different pattern of etiology to that seen in older children. The clinical management of such children, in terms of investigation, optical correction, and use of myopia control treatments, is a complex and often multidisciplinary process.

Risk of Neurotoxicity with Multiple General Anaesthetics for Examination Under Anaesthesia in Paediatric Ophthalmology - A Cause for Concern?

Purpose: To evaluate the impact of clinical protocol change via active minimisation on the number of general anaesthetic (GA)/sedation episodes for diagnostic ophthalmic purposes at Children's Health Ireland at Temple Street (CHI-TS), Dublin, Ireland, from 2016 to 2019, inclusive. Change was implemented following published cautionary principles in 2016 by the FDA regarding the potential neurotoxic risk from multiple GA exposure in children. Methods: Retrospective analysis of electronic operating theatre records was completed using procedure codes "Ophthalmological examination" and "Examination of fundi". Available records for patients undergoing multiple examination under anaesthesia (EUA) procedures were assessed for demographics, indication. Comparison was made regarding overall EUA numbers and breakdown for each year, before and after the new departmental approach. From 2018 onward, a patient-centred, departmental strategy of active minimisation of EUA was adopted, using strategies of "training, technology and patience". A literature review was conducted using online databases. Results: A total of 450 EUAs were performed over the 4 years investigated. In the former 2 years of the study period, prior to departmental policy change, EUAs represented 32% (304 of 948 total theatre episodes) of the ophthalmic theatre caseload. In the latter 2 years of this study period, this proportion fell to 19% (146 EUAs of 783 theatre episodes). Total theatre case numbers were comparable in both time periods. Eighteen children had multiple EUAs (ie, ≥2 EUAs, mean 6.5, SD 2.9) for life/sight threatening indications, totalling 116 EUAs (25.7%). Conclusion: A significant reduction in diagnostic EUA volume was accomplished resulting in reduced individual patient risk and increased capacity for surgical interventions. A detailed description of this methodology is included for the purposes of replication at comparable units. EUA will continue to play a crucial role in the management of life/sight threatening conditions but the application of a cautionary principle to reduce EUA, where possible, is appropriate to reduce potential for neurotoxicity.

The WHO-ITU MyopiaEd Programme: A Digital Message Programme Targeting Education on Myopia and Its Prevention.

The objective of this paper is to provide an overview of the World Health Organization - International Telecommunication Union MyopiaEd programme - a digital message programme targeting education on myopia and its prevention. The development of the MyopiaEd programme included 4 key steps: (1) Conceptualization and consultation with experts in the field of myopia, mHealth and health behavior change; (2) Creation of SMS message libraries and programme algorithm; (3) Review of the message libraries to ensure relevance to the target audience; and (4) Pre-testing amongst end-user groups to ensure that the design of the programme and the message content were understandable. After reviewing the available evidence and considering input of the experts, the aims, end users and key themes of the programme were finalized. Separate SMS-adapted message libraries were developed, reviewed and pre-tested for four target end-user groups; (1) general population involved in the care of children (2) parents or caregivers of children with myopia; (3) adolescents with myopia; and (4) adults with myopia. The message libraries are part of a comprehensive toolkit, developed through a consultative process with experts in digital health, to support implementation within countries. The development of the MyopiaEd programme aims to provide a basis for Member States and other stakeholders to develop, implement and monitor large-scale mHealth programmes. It is aimed at raising awareness of good eye care behaviors and addressing common reasons for non-compliance to spectacle wear. The next steps will involve adapting and evaluating the MyopiaEd programme in selected settings.

The relationship between serum zinc levels and myopia.

CLINICAL SIGNIFICANCE: Nutritional status influences growth and development, including that of the eye. However, little attention has been given to possible dietary influences in myopia. This study demonstrates that serum zinc has no relationship with myopia development. BACKGROUND: Myopia is inherently associated with eye growth and thereby possibly amenable to nutritional influence. A number of Asian studies have reported lower levels of serum zinc in myopic children. This study was designed to assess the relationship between serum zinc and myopia in the Korean population - using a subsample of participants from nationally representative data. METHODS: Data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES) 2010 were used to explore zinc status in relation to refraction. A total of 304 participants were analysed, ranging in age from 12 to 19-years. Serum zinc levels were measured using inductively coupled plasma mass spectrometry, while refractive error was determined by non-cycloplegic autorefraction. Multivariate analysis was used to examine the association. RESULTS: A significant majority of participants (n = 255; 84 per cent) were myopic. There was no significant difference in serum zinc levels between myopic and non-myopic children (p = 0.81). In multivariate logistic regression, serum zinc was not significantly associated with myopia after adjustment for age, gender, residence, body mass index, family income and recreational activity. Similarly, no relationship was observed between spherical equivalent refraction and serum zinc within the myopic group (p = 0.46). CONCLUSION: In a subset of 12-19-year-old participants from the population-representative KNHANES study, no association was found between serum zinc and myopia. However, the lack of a sensitive biomarker for zinc status remains a major limitation in this, and all current studies.

What can anisometropia tell us about eye growth?

BACKGROUND/AIMS: Both eyes of one individual share the same environment and genes. We examined interocular differences in biometry to determine the potential role of other factors in refractive development. METHODS: 362 subjects (6-7 years) from the Northern Ireland Childhood Errors of Refraction study were studied. Cycloplegic autorefraction was measured with a Shin-Nippon open-field autorefractor. Axial length and corneal curvature were measured with a Zeiss IOLMaster. RESULTS: 257 subjects had an interocular difference of <0.50 D (ISO group) and 105 (29%) a difference of ≥0.50 D (ANISO group). Twenty-five subjects (6.9%) had anisometropia ≥1.00 D and 9 (2.5%) had anisometropia ≥1.50 D. The two groups, ISO and ANISO, showed different refractive distributions (p=0.001) with the ISO group showing a nearly Gaussian distribution and the ANISO group showing positive skew, a hyperopic shift and a bi-Gaussian distribution. A marker of emmetropisation is the poor correlation between refraction and corneal curvature seen in older children. There was no significant correlation between refraction and corneal curvature of each eye in the ISO group (r=0.09, p=0.19), but these parameters were significantly correlated in the ANISO group (r=0.28, p=0.004). CONCLUSION: In young children, small degrees of anisometropia (≥0.5 D) are associated with impaired emmetropisation. This suggests that anisometropia is a marker for poorly regulated eye growth, indicating that, in addition to environmental and genetic influences on eye growth, stochastic processes contribute to refractive outcomes.

Macular Pigment Optical Density Fluctuation as a Function of Pupillary Mydriasis: Methodological Considerations for Dual-Wavelength Autofluorescence.

PURPOSE OF THE STUDY: Macular pigment (MP), comprising the dietary carotenoids lutein, zeaxanthin and meso-zeaxanthin, is believed to benefit eye health and vision. Numerous clinical and research devices and techniques are currently available to facilitate MP optical density (MPOD) measurement. One of those techniques, dual-wavelength fundus autofluorescence (AF) is being increasingly used for measurement of MP in the eye. There is substantial methodological variation across the published studies that have employed this technique, including in relation to the use of mydriasis, the possible influence of which does not appear to have been addressed in the literature. This prospective cross-sectional study was designed to investigate the effect of mydriasis on MP measurement quality and MPOD values obtained with dual-wavelength AF using the Heidelberg Spectralis HRA+OCT device. MATERIALS AND METHODS: Twenty-one healthy participants were recruited to the study. The mean age of participants was 44.8 years (± 14.63). Pupil size and MPOD were measured in one eye for each participant, initially under natural pupil conditions and subsequently 30 minutes following instillation of one drop of 0.5% tropicamide. RESULTS: Despite providing MPOD measurements for the majority of undilated eyes (85.7% of eyes herein), pupillary dilation resulted in statistically significant changes in MPOD (p < .001 for central eccentricities). Our results indicate that the changes in MPOD were not uniform across the spatial profile. Marked improvements were also observed in image quality post-dilation (p < .002 for central eccentricities). CONCLUSIONS: This study clearly demonstrates that dual-wavelength AF measurements of MPOD in the same eye vary as a function of pupillary dilation status, with MPOD under-estimated across the entire spatial profile of MP for natural relative to dilated pupillary conditions. Mydriasis should, therefore, be used routinely for MPOD measurements using dual wavelength AF, pupil size should be reported and image quality optimized in order to ensure accurate MPOD quantification.

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

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

Low-dose (0.01%) atropine eye-drops to reduce progression of myopia in children: a multicentre placebo-controlled randomised trial in the UK (CHAMP-UK)-study protocol.

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.

Association of Total Zinc Intake with Myopia in U.S. Children and Adolescents.

SIGNIFICANCE: This present study advances our knowledge on the role of lifestyle factors in myopia (short-sightedness), specifically dietary factors. It has been suggested in previous studies that lower zinc status is associated with myopia; however, this article shows no relationship between dietary zinc intake and myopia in U.S. adolescents. PURPOSE: It has been suggested that low zinc levels may contribute to the development of myopia. The aim of the present study is to examine, for the first time in a Western population, the association of total dietary and supplement zinc intake with myopia. METHODS: A total of 1095 children/adolescents aged 12 to 19 years who participated in the U.S. National Health and Nutrition Examination Survey from 2007 to 2008 were enrolled in this study. Multivariate logistic regression analysis was performed to examine the relationship between total zinc intake and myopia after adjustment for potential confounders. In addition, the association between total zinc intake and spherical equivalent refractive error was examined in the myopia group through multiple linear regression. RESULTS: Among study participants, 30% were found to be myopic (≤-1.00 D). Although median total daily zinc intake was lower among myopes (10.8 [10.2] mg/d) than among nonmyopes (11.1 [10.8] mg/d), the difference was not statistically significant (P = .11). In multiple logistic regression analyses, zinc and copper intakes were not significantly associated with myopia after adjustment for age, sex, body mass index, ethnicity, family income, recreational activity, copper intake, and daily energy intake (in kilocalories per day). In multiple linear regression, spherical equivalent refractive error was not associated with total zinc intake in the myopic group after adjustment for confounding factors (P = .13). CONCLUSIONS: In contrast to previous Asian studies, total zinc intake is not associated with the presence of myopia in U.S. adolescents/children.

Is optometry ready for myopia control? Education and other barriers to the treatment of myopia.

Background: With the increasing prevalence of myopia there is growing interest in active myopia control. However, the majority of progressive myopes are still prescribed single vision spectacles. This prospective study aims to elucidate the knowledge and attitudes of optometrists toward myopia control, and thereby identify perceived barriers to the implementation of a risk focussed model of myopia management. Methods: A series of four focus group discussions were conducted involving optometrists in different settings and career stages. Results: The key finding to emerge is a clear disconnect between academic optometrists, optometry students and clinicians in practice. Academic faculty considered themselves competent in managing progressive myopia and believed the optometry curriculum provides undergraduates with sufficient clinical skills and knowledge to practise myopia control. Final-year optometry students regarded themselves as knowledgeable about myopia control but lack confidence in their ability to practise myopia control, with only one student indicating they would initiate myopia control therapy. The majority of clinicians do not offer myopia control treatments, other than to communicate lifestyle advice to modify risk of myopia progression. Clinicians alluded to a lack of availability of myopia control interventions and identified a range of barriers relating to their training, clinical practice and public health challenges, financial, technological and other constraints that affect the implementation of such interventions. Conclusion: It appears optometrists have to yet embrace myopia control as a core element of the clinical eye care service they provide. Education, training, finance, and time restrictions, as well as limited availability of myopia control therapies were among the main perceived barriers to myopia control. This study revealed a distinct need for alignment between optometric training and the public health need for effective myopia control.

Myopia Outcome Study of Atropine in Children (MOSAIC): an investigator-led, double-masked, placebo-controlled, randomised clinical trial protocol.

Background: The Myopia Outcome Study of Atropine in Children (MOSAIC) aims to explore the efficacy, safety, acceptability and mechanisms of action of 0.01% unpreserved atropine for myopia control in a European population. Methods: MOSAIC is an investigator-led, double-masked, placebo-controlled, randomised clinical trial (RCT) investigating the efficacy, safety and mechanisms of action of 0.01% atropine for managing progression of myopia. During Phase 1 of the trial, 250 children aged 6-16 years with progressive myopia instil eye drops once nightly in both eyes from randomisation to month 24. No treatment is given during Phase 2 from month 24 to 36 (washout period) for those participants initially randomised to the intervention arm (n=167), during which any potential rebound effects on cessation of treatment will be monitored. All participants initially assigned to the placebo (n=83) crossover to the intervention arm of the study for Phase 2, and from month 24 to 36, instil 0.01% atropine eye drops in both eyes once nightly. Further treatment and monitoring beyond 36 months is planned (Phase 3) and will be designed dependent on the outcomes of Phase 1. Results: The primary outcome measure is cycloplegic spherical equivalent refractive error progression at 24 months. Secondary outcome measures include axial length change as well as the rebound, safety and acceptability profile of 0.01% atropine. Additional analyses will include the mechanisms of action of 0.01% atropine for myopia control. Conclusions: The generalisability of results from previous clinical trials investigating atropine for myopia control is limited by the predominantly Asian ethnicity of previous study populations. MOSAIC is the first RCT to explore the efficacy, safety and mechanisms of action of unpreserved 0.01% atropine in a predominantly White population. Trial registration: ISRCTN: ISRCTN36732601 (04/10/2017), EudraCTdatabase 2016-003340-37 (03/07/2018).

Corneal Surface Ablation Laser Refractive Surgery for the Correction of Myopia: A Network Meta-analysis.

PURPOSE: To systematically compare the efficacy, predictability, safety, postoperative haze, pain scores, and epithelial healing time of four corneal surface ablation procedures. METHODS: PubMed, Embase, Cochrane Library, and the U.S. trial registry were searched up to June 2018. Randomized controlled trials were selected. Efficacy (uncorrected distance visual acuity of 20/20 or better), predictability (refractive spherical equivalent within ±0.50 diopters [D] of the target), and safety (loss of two or more lines of spectacle corrected distance visual acuity) were set as primary outcome measures. Haze, pain scores, and epithelial healing time were set as secondary outcome measures. RESULTS: Eighteen studies involving 1,423 eyes were included. According to the Grading of Recommendations Assessment, Development, and Evaluation, the quality of outcomes were moderate to high (70.6%). There were no differences in efficacy, predictability, safety, haze, day 1 pain, and epithelial healing time between treatments. Epithelial laser in situ keratomileusis (epi-LASIK) had statistically significantly higher pain scores on day 3 compared to photorefractive keratectomy (PRK) (weighted mean differences [WMD] = 2.2, 95% credible intervals [CrI] = 0.19 to 4.01) and transepithelial PRK (T-PRK) (WMD = 2.7, 95% CrI = 0.51 to 4.84). The surface under the cumulative ranking curve ranking results (best to worst) showed laser epithelial keratomileusis (LASEK) ranked highest for efficacy, predictability, safety, and day 1 pain scores. Epi-LASIK ranked best for grade 1 haze scores. T-PRK ranked best for haze of 0.5 or higher, haze scores day 3 pain scores, and epithelial healing time. CONCLUSIONS: Surface laser refractive surgeries are comparable in terms of efficacy, predictability, safety, and postoperative haze except for day 3 pain scores, with epi-LASIK being more painful compared to PRK and T-PRK. [J Refract Surg. 2018;34(11):726-735.].

Parental attitudes to myopia: a key agent of change for myopia control?

PURPOSE: With the increasing prevalence in myopia there is growing interest in active myopia prevention. This study aims to increase our understanding of parental attitudes to myopia development and control, as a means to inform future health planning and policy. It evaluates, for the first time, the attitude of parents to myopia and its associated risks, as well as assessing the exposure of Irish children to environmental factors that may influence their risk profile for myopia development. METHODS: Parents of 8-13 year old children in eight participating schools completed a questionnaire designed to assess their knowledge of and attitudes towards myopia and its risk factors. A structured diary was also used to capture daily activities of children in relation to myopia risk factors. RESULTS: Of 329 parents, just 46% considered that myopia presented a health risk to their children, while an identical number (46%) regarded it as an optical inconvenience. Myopia was also, but less frequently, considered an expense (31% of parents), a cosmetic inconvenience (14% of parents) and, by some, as a sign of intelligence (4% of parents) 76% of parents recognised the potential of digital technology to impact the eye, particularly as a cause of eyestrain and need for spectacles. Only 14% of parents expressed concern should their child be diagnosed with myopia. Compared to non myopic parents, myopic parents viewed myopia as more of an optical inconvenience (p < 0.001), an expense (p < 0.005) and a cosmetic inconvenience (p < 0.001). There was a trend for myopic parents to limit screen time use in their household more than non-myopic parents (p = 0.05). Parents who considered myopia a health risk sought to limit screen time more than parents who did not regard myopia as a health risk to their child (p = 0.01). Children spent significantly longer performing indoor proximal tasks (255 min) compared to time spent outdoors (180 min; p < 0.0001) daily. Older (p = 0.001), urban (p = 0.0005) myopic (=0.04) children spent significantly more time at digital screens compared to younger non-myopic children from a rural background. CONCLUSION: Parental attitudes to myopia were typically nonchalant in relation to health risk. This is of particular concern given the impact parents have on children's behaviour and choices with respect to such risk factors, demonstrating an acute need for societal sensitisation to the public health importance of myopia.

Postoperative Efficacy, Predictability, Safety, and Visual Quality of Laser Corneal Refractive Surgery: A Network Meta-analysis.

PURPOSE: To compare the postoperative efficacy, predictability, safety, and visual quality of all major forms of laser corneal refractive surgeries for correcting myopia. DESIGN: Systematic review and network meta-analysis. METHODS: Search of MEDLINE, EMBASE, Cochrane Library, and the US trial registry was conducted up to November 2015. Randomized controlled trials (RCT) reporting in accordance with the eligibility criteria were included in this review. We performed a Bayesian random-effects network meta-analysis. RESULTS: Forty-eight RCTs were identified. For efficacy (uncorrected visual acuity [UCVA]), there were no statistically significant differences between any pair of treatments analyzed. The SUCRA (surface under the cumulative ranking curve) ranking (from best to worst) was femtosecond-based laser in situ keratomileusis (FS-LASIK), LASIK, small-incision lenticule extraction, femtosecond lenticule extraction (FLEx), photorefractive keratectomy (PRK), laser epithelial keratomileusis (LASEK), epipolis (Epi)-LASIK, transepithelial PRK (T-PRK). For predictability (refractive spherical equivalent [SE]), a statistically significant difference was found when FS-LASIK was compared with LASIK (odds ratio [OR] 2.29, 95% credible interval [CrI] 1.20-4.14), PRK (OR 2.16, 95% CrI 1.15-4.03), LASEK (OR 2.09, 95% CrI 1.08-4.55), and Epi-LASIK (OR 2.74, 95% CrI 1.11-6.20). The SUCRA ranking (from best to worst) was FS-LASIK, T-PRK, LASEK, PRK, LASIK, Epi-LASIK. There were no statistically significant differences in the safety (best spectacle-corrected visual acuity) comparisons. For both postoperative higher-order aberrations (HOAs) and contrast sensitivity (CS), there were no statistically significant differences between any pair of treatments analyzed. The SUCRA ranking results show that some corneal surface ablation techniques (PRK and LASEK) rank highest. CONCLUSIONS: This network meta-analysis shows that there were no statistically significant differences in either visual outcomes (efficacy and safety) or visual quality (HOAs and CS). FS-LASIK behaved better in predictability than any other type of surgeries.