Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis

Abstract Background Reports of frequent manifestation of allergic diseases in children with attention deficit hyperactivity disorder (ADHD) have been the subject of mounting clinical interest. However, evidence supporting the association between ADHD and allergies is inconsistent and has yet to be systematically reviewed. The objective of this study was to compile and assess available studies on the association between ADHD and allergic diseases in children. Methods A comprehensive search using MEDLINE, EMBASE, the Cochrane library, and CINAHL databases was completed in 23 November 2015. The inclusion criteria for studies were that the research assessed allergic diseases in children, 18 years of age and younger, with a diagnosis of ADHD and that a distinct comparison group was incorporated. Any comparative studies, encompassing both randomized controlled trials and observational studies, were considered for inclusion. Two review authors independently assessed the quality of the selected studies by the use of validated assessment tools, performed data extraction and conducted meta-analysis according to Cochrane Collaboration guidelines. Results Five eligible studies were included in this systematic review. Of these studies, three were case-control and two were cross sectional studies. A majority of information from the five studies was classified as having low or unclear risk of bias. The meta-analysis showed an association between children with ADHD and asthma compared with the control groups (OR: 1.80, 95% CI: 1.57 - 2.07; five studies, low quality of evidence), but did not indicate an association between food allergy and ADHD (OR: 1.13, 95% CI: 0.88 - 1.47; three studies very low quality of evidence). The odds of experiencing allergic rhinitis, atopic dermatitis, and allergic conjunctivitis were slightly higher in children with ADHD compared with control groups, though a substantial statistical heterogeneity was notable in the overall effect estimates. Conclusions The findings from this review and meta-analysis show that children with ADHD are more likely to have asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis than their counterparts. Interventions including strategies for managing allergies in children with ADHD would be beneficial

High Myopia and Its Associated Factors in JPHC-NEXT Eye Study: A Cross-Sectional Observational Study

The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤-6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample

Effects of Hyperoxia on the Refraction in Murine Neonatal and Adult Models

Whether hyperoxia affects the refraction in neonatal and adult mice is unknown. The mice exposed to 85% oxygen at postnatal 8 days (P8d) for 3 days and the mice exposed to normal air were assigned to the neonatal hyperoxia and normoxia groups, respectively. The refraction, the corneal curvature radius (CR) and the axial length (AL) were measured at P30d and P47d. Postnatal 6 weeks (P6w) adult mice were divided into the adult hyperoxia and normoxia groups. These parameters were measured before oxygen exposure, after 1 and 6 weeks, and every 7 weeks. The lens elasticity was measured at P7w and P26w by enucleation. The neonatal hyperoxia group showed a significantly larger myopic change than the neonatal normoxia group (P47d −6.56 ± 5.89 D, +4.11 ± 2.02 D, p < 0.001), whereas the changes in AL were not significantly different (P47d, 3.31 ± 0.04 mm, 3.31 ± 0.05 mm, p = 0.852). The adult hyperoxia group also showed a significantly larger myopic change (P12w, −7.20 ± 4.09 D, +7.52 ± 2.54 D, p < 0.001). The AL did not show significant difference (P12w, 3.44 ± 0.03 mm, 3.43 ± 0.01 mm, p = 0.545); however, the CR in the adult hyperoxia group was significantly smaller than the adult normoxia group (P12w, 1.44 ± 0.03 mm, 1.50 ± 0.03 mm, p = 0.003). In conclusion, hyperoxia was demonstrated to induce myopic shift both in neonatal and adult mice, which was attributed to the change in the CR rather than the AL. Elucidation of the mechanisms of hyperoxia and the application of this result to humans should be carried out in future studies

Efficacy of the Newly Invented Eyelid Clamper in Ultra-Widefield Fundus Imaging

Background: Ultra-widefield fundus imaging is widely used for obtaining wide angle images of the retina in one single image. Although it has a potential to obtain a wide area of retinal photographs, images are often obstructed by eyelashes or eye lids. In this study, we used a newly invented eyelid clamper, which can keep an eye open without touching conjunctiva or lid margin, to assess the efficacy in clinical use by comparing with conventional tape fixation. Methods: Ultra-widefield fundus images were captured with an ultra-widefield imaging system in 19 patients who visited to the outpatient clinic of Department of Ophthalmology, Keio University Hospital with the eyelid clamper or a conventional tape fixation. The area of imaged retinas was outlined and quantified with pixels. After obtaining images, patients answered a questionnaire. Results: The average number of pixels in total areas with the eyelid clamper or with tape fixation were 4.31 ± 0.35 and 4.32 ± 0.34 mega pixels, respectively, showing no significant difference between the groups (p = 0.889). The average face pain scale of the eyelid clamper was 1.13 on a scale of 0 to 5. The number of patients who did not feel any pain was nine (47.4%). Conclusions: The eyelid clamper can be applied in clinical setting and can better support obtaining sufficiently wide fundus images compared to a conventional tape fixation

Fenofibrate Protects against Retinal Dysfunction in a Murine Model of Common Carotid Artery Occlusion-Induced Ocular Ischemia

Ocular ischemia is a common cause of blindness and plays a detrimental role in various diseases such as diabetic retinopathy, occlusion of central retinal arteries, and ocular ischemic syndrome. Abnormalities of neuronal activities in the eye occur under ocular ischemic conditions. Therefore, protecting their activities may prevent vision loss. Previously, peroxisome proliferator-activated receptor alpha (PPARα) agonists were suggested as promising drugs in ocular ischemia. However, the potential therapeutic roles of PPARα agonists in ocular ischemia are still unknown. Thus, we attempted to unravel systemic and ocular changes by treatment of fenofibrate, a well-known PPARα agonist, in a new murine model of ocular ischemia. Adult mice were orally administered fenofibrate (60 mg/kg) for 4 days once a day, followed by induction of ocular ischemia by unilateral common carotid artery occlusion (UCCAO). After UCCAO, fenofibrate was continuously supplied to mice once every 2 days during the experiment period. Electroretinography was performed to measure retinal functional changes. Furthermore, samples from the retina, liver, and blood were subjected to qPCR, Western blot, or ELISA analysis. We found that fenofibrate boosted liver function, increased serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the central nervous system, and protected against UCCAO-induced retinal dysfunction. Our current data suggest a promising fenofibrate therapy in ischemic retinopathies

Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice

The natural carotenoid crocetin has been reported to suppress phenotypes of an experimental myopia model in mice. We investigated the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a −30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage. A concentration of 0.001% of crocetin-containing chow showed a significant (p < 0.001) suppressive effect against both refractive and AL changes in the murine model. Meanwhile, there was no significant difference of AL change between the 0.0003% and the normal chow groups. The concentration of crocetin in the plasma and the eyeballs from mice fed with 0.001% crocetin-containing chow was significantly higher than control and 0.0003% crocetin-containing chow. In conclusion, we suggest 0.001% of crocetin-containing extract is the minimum effective dose showing a significant suppressive effect against both refractive and AL changes in the murine model

Ocular-Component-Specific miRNA Expression in a Murine Model of Lens-Induced Myopia

To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation

Effect of Violet Light-Transmitting Eyeglasses on Axial Elongation in Myopic Children: A Randomized Controlled Trial

The fact that outdoor light environment is an important suppressive factor against myopia led us to invent violet light-transmitting eyeglasses (VL glasses) which can transmit violet light (VL), 360–400 nm in wavelength, for the suppression of myopia, and can meanwhile block harmful ultraviolet waves from sunlight. The current study is a double-blinded randomized clinical trial to investigate the myopia-suppressive effect of VL glasses compared to conventional eyeglasses (placebo glasses) that do not transmit VL. The subjects were children aged from 6 to 12 years old, the population in which myopia progression is generally accelerated, and the myopia suppressive effect was followed up for two years in a city in Japan. Periodical ophthalmic examinations, interviews, and measurements of reflection and axial length under mydriasis were performed at the initial visit (the baseline) and at 1, 6, 12, 18, and 24 months. The mean change in axial length in the VL glasses group was significantly smaller than in the placebo glasses group when time for near-work was less than 180 min and when the subjects were limited to those who had never used eyeglasses before this trial (p < 0.01); however, this change was not significant without subgrouping. The suppressive rate for axial elongation in the VL glasses group was 21.4% for two years