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SIX1/SIX6 polymorphism has been shown to be associated with glaucoma. Studies have also found that, in older adults, retinal nerve fibre layer (RNFL) thickness is significantly thinned with each copy of the risk allele in SIX1/SIX6. However, it is not known whether these genetic variants exert their effects in younger individuals. Comparing a healthy young adult with an older adult cohort (mean age 20 vs 63 years), both of Northern European descent, we found that there was no significant RNFL thinning in each copy of the risk alleles in SIX1/SIX6 in the eyes of younger individuals. The older cohort showed an unexpectedly thicker RNFL in the nasal sector with each copy of the risk allele for both the SIX1 (rs10483727) and SIX6 (rs33912345) variants. In the temporal sector, thinner RNFL was found with each copy of the risk allele in rs33912345 with a decrease trend observed in rs10483727. Our results suggest that SIX1/SIX6 gene variants exert their influence later in adult life.

Precis: Although mental or emotional stress may result raise in intraocular pressure (IOP) we found weak associations between endogenous stress markers concentrations and retinal nerve fiber layer (RNFL) thickness, thus limited evidence that stress affects retinal ganglion cells integrity., Purpose: Increased exposure to glucocorticoids is linked to elevated IOP, which is a risk factor for glaucoma. We explored the RNFL thickness for changes that may mimic preclinical glaucomatous changes, in relation to the hormonal stress response., Materials and Methods: Young healthy adults (n=863) underwent a Trier Social Stress Test. Endogenous plasma adrenocorticotropic hormone (ACTH) and cortisol were measured for those who provided biological samples, and adrenal sensitivity was calculated. On the basis of cortisol levels before and after the Trier Social Stress Test, participants were categorized into one of 3 stress response types: anticipatory-responders, reactive-responders, and nonresponders. Participants underwent an eye examination that included spectral-domain optical coherence tomography to measure peripapillary RNFL thickness., Results: Higher levels of ACTH were associated with thinner RNFL globally (P=0.009), and at the inferotemporal (P=0.015), superotemporal (P=0.044), and temporal sectors (P=0.046). Lower adrenal sensitivity was associated with thinner RNFL inferotemporally (P<0.001) and temporally (P=0.037). However, these effect sizes were small; for example, a 10 pg/mL increase in baseline ACTH was associated with only a 3 µm thinner RNFL. RNFL thickness was not associated with plasma cortisol levels and or significantly different between groups of acute stress response patterns., Conclusions: Although there was a link between ACTH or adrenal sensitivity and RNFL thickness, this association was weak and its clinical significance is unclear. Despite the close associations between levels of endogenous stress markers and IOP, we found limited evidence of a link to RNFL integrity.

Purpose: To describe the choroidal thickness (ChT) in a large sample of young adults with the aim of establishing a normative ChT profile reference in this demographic cohort and explore its association with best-corrected visual acuity (BCVA)., Design: Cross-sectional study., Methods: From a single center, 741 young adults (19-30 years of age, 49% male) were recruited to undergo a comprehensive ophthalmic examination, including BCVA measurement, post-cycloplegic autorefraction, ocular biometry, tonometry, and spectral-domain optical coherence tomography (SD-OCT) imaging. The enhanced depth imaging mode on the SD-OCT was used. The main outcome measure was the central macular ChT (0.5-mm radius around the fovea). The ChTs at the inner (between 0.5-mm and 1.5-mm radius) and outer macular rings (between 1.5-mm and 2.5-mm radius) were also measured., Results: The median central macular ChT was 370 μm (interquartile range 312-406 μm). The choroid was thickest at the superior-inner, inferior-inner, and central macular regions (370-373 μm) and thinnest nasally at the outer macular region (median 256 μm). Decreased central macular ChT was associated with younger age, female sex, nonwhite ethnicities, and myopia (P ≤ .013). There was a significant association between better BCVA and increased central macular ChT (P < .001), after adjusting for age, sex, ethnicity, and ocular measures. His relationship was only apparent in eyes with central macular ChTs <300 μm (P = .019) and absent in eyes with ChTs >300 μm., Conclusions: The central ChT of young adults was 370 μm. There was a significant association between worse BCVA and thinner choroids below a threshold of 300 μm, raising the possibility that ChT could be predictive of visual function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Potential links may exist between vitamin A intake and myopia via various pathways. In this study, we examined the association between dietary vitamin A intake during adolescence and myopia in early adulthood., Methods: We performed a prospective analysis utilizing data collected from participants of the Raine Study Gen2. Dietary vitamin A intake, determined via food frequency questionnaires completed at ages 14, 17, and 20 years, was compared with ophthalmic measurements collected at year 20. Low vitamin A levels were defined as <600 µg/day. Regression models were used to adjust for ocular sun exposure level, educational level, and parental myopia as potential confounders., Results: A total of 642 subjects were analyzed. Although those with adequate vitamin A intakes were less likely to be myopic ( P = 0.03), this association became insignificant when adjusted for potential confounding factors in logistic regression modeling (odds ratio, 0.59; 95% confidence interval, 0.98-2.52; P = 0.06)., Conclusions: There were no significant associations between total vitamin A intakes during adolescence and year 20 refractive errors after adjustment for confounders. Replication of this finding and further investigations are essential to rule out the suggestion that sufficient vitamin A intake during adolescence is associated with lower risk of myopia in early adulthood., Translational Relevance: Our findings are not definitive that ingesting foods high in vitamin A during childhood and adolescence does not have a role for preventing myopia in early adulthood., Competing Interests: Disclosure: F.J. Ng, None; D.A. Mackey, None; T.A. O'Sullivan, None; W.H. Oddy, None; S. Yazar, None, (Copyright 2020 The Authors.)

Background: Recent changes in communication technologies, including increased reliance on mobile phones and the internet, may present challenges and/or opportunities to re-engaging inactive study cohorts. We evaluate our ability to recruit participants for the Kidskin Young Adult Myopia Study (KYAMS), a follow-up of the Kidskin Study., Methods: KYAMS participants were recruited from the Kidskin Study, a sun exposure-intervention study for 5-6 year-olds running from 1995 to 1999 with most recent follow-up in 2005. From 2015 to 2019, the KYAMS used mail-outs, phone calls and social media to contact Kidskin Study participants. Multivariable logistic regression was used to identify variables associated with successful contact of a Kidskin Study participant or family member and KYAMS participation., Results: Of 1695 eligible participants, 599 (35.5%) participants (or a family member) were contacted and 303 (17.9%) participated in the KYAMS. KYAMS participation was more likely in those who participated in the 2005 follow-up (odds ratio [OR] = 5.09, 95% confidence interval [CI]: 3.67-7.06) and had a mobile phone number on record (OR = 2.25, CI: 1.57-3.23). Of those contacted, participants who were the first point of contact (OR = 4.84, CI: 2.89-8.10) and who were contacted by letter in the first (OR = 6.53, CI: 3.35-12.75) or second (OR = 5.77, CI: 2.85-11.67) round were more likely to participate in the KYAMS, compared to contact by landline phone., Conclusions: We recruited approximately one-fifth of Kidskin Study participants for the KYAMS. Participants were more likely to participate in the KYAMS if they were contacted directly, rather than through a family member, and if they were contacted by invitation letter., Trial Registration: ACTRN12617000812392.

PRéCIS:: This study found an association between thinner superotemporal retinal nerve fiber layer (RNFL) and obstructive sleep apnea (OSA). However, the lack of association of sleep apnea with other disc measures does not support a link with glaucoma., Aim: Previous findings on the link between OSA and increased glaucoma risk have been inconsistent. In a community-based study of middle-aged and older adults, we explored for differences in optic disc measures that may resemble preclinical glaucomatous changes in relation to OSA status and severity., Methods: A total of 865 participants (46 to 67 y; 45% male) underwent an at-home sleep study during which their apnea-hypopnea index (AHI) and sleep oxygen saturation level were measured. Participants were determined to have no OSA (AHI<5 events/h), mild (AHI 5 to 15), moderate (AHI 16 to 30), or severe OSA (AHI>30). At a 6-year follow-up visit, the optic discs of both eyes were imaged using spectral domain optic coherence tomography to measure the Bruch membrane opening-minimum rim widths and RNFL thicknesses., Results: On the basis of the AHI, 411 participants (48%) had OSA, of whom 92 (11% of total sample) and 26 (3%) had moderate and severe OSA, respectively. In the multivariate analysis, participants with severe OSA had thinner RNFL superotemporally than those without OSA or with mild OSA (P<0.001 and 0.001, respectively). In addition, superotemporal RNFL was inversely associated with AHI (P=0.004) and sleep time with oxygen saturation level <90% (P=0.005). There was no association between OSA measures and Bruch membrane opening-minimum rim widths., Conclusions: Our findings do not provide strong evidence of a link between measures of OSA and the optic disc. However, the association between increased OSA severity and thinner superotemporal RNFL has been reported consistently in previous studies and thus warrants further evaluation.

Myopia is an increasingly common condition that is associated with significant costs to individuals and society. Moreover, myopia is associated with increased risk of glaucoma, retinal detachment and myopic maculopathy, which in turn can lead to blindness. It is now well established that spending more time outdoors during childhood lowers the risk of developing myopia and may delay progression of myopia. There has been great interest in further exploring this relationship and exploiting it as a public health intervention aimed at preventing myopia in children. However, spending more time outdoors can have detrimental effects, such as increased risk of melanoma, cataract and pterygium. Understanding how spending more time outdoors prevents myopia could advance development of more targeted interventions for myopia. We reviewed the evidence for and against eight facets of spending time outdoors that may protect against myopia: brighter light, reduced peripheral defocus, higher vitamin D levels, differing chromatic spectrum of light, higher physical activity, entrained circadian rhythms, less near work and greater high spatial frequency (SF) energies. There is solid evidence that exposure to brighter light can reduce risk of myopia. Peripheral defocus is able to regulate eye growth but whether spending time outdoors substantially changes peripheral defocus patterns and how this could affect myopia risk is unclear. Spectrum of light, circadian rhythms and SF characteristics are plausible factors, but there is a lack of solid evidence from human studies. Vitamin D, physical activity and near work appear unlikely to mediate the relationship between time spent outdoors and myopia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the prevalence of amblyopia, strabismus, and anisometropia in a young adult population at a single center in Australia and to investigate the underlying prenatal and early-life risk factors., Methods: Participants in the Raine Study have been followed from mid-gestation (n = 2,868 newborns) to young adulthood. At age 20 years, 1,344 participants had a comprehensive eye examination, including visual acuity and a detailed orthoptic assessment. Risk factors were determined from medical records and questionnaires completed by the mothers at 18 weeks' gestation. The main outcome measures were the proportions of participants with amblyopia, esotropia, exotropia, or anisometropia (defined as >1 D difference)., Results: Of the 1,125 white participants, 12 (1.1%) had amblyopia, 39 (3.5%) had strabismus, and 33 (2.9%) had anisometropia. In multivariable logistic regression, amblyopia was associated with a maternal history of pregnancy-induced hypertension (OR = 3.80; 95% CI, 1.19-12.13); esotropia, with lower gestational age (OR = 0.97; 95% CI, 0.95-0.97) and a heavier placenta (OR = 1.02; 95% CI, 1.00-1.04); exotropia, with a maternal history of previously treated hypertension (OR = 4.00; 95% CI, 1.06-15.03) and maternal use of recreational drugs during early pregnancy (OR = 3.61; 95% CI, 1.06-15.03); and anisometropia, with older maternal age (OR = 1.07; 95% CI, 1.01-1.14) and an abnormal umbilical cord (OR = 2.39; 95% CI, 1.04-5.47)., Conclusions: The prevalence of amblyopia, strabismus, and anisometropia in this cohort was similar to that in other studies. Preterm birth and maternal health may have adverse effects on eye development., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Introduction: Eye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989-1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes., Methods and Analysis: Participants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters., Ethics and Dissemination: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences., Trial Registration Number: ACTRN12617001599369; Active, not recruiting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

To examine the impact of sun exposure on human health, accurate measures of past sun exposure are required. We investigated how young adults' recall of childhood sun-related behaviours compares with parent-reported measures collected during childhood. The Kidskin-Young Adult Myopia Study (KYAMS) is a follow-up of the Kidskin Study, a sun-protection intervention study conducted from 1995-2001. KYAMS participants, aged 25-30 years, reported time in sun, and use of hats and sunscreen, for each year from ages 5-26 years (n = 244). Using weighted kappa, we assessed agreement between these data and corresponding variables derived from the Kidskin Study parent questionnaires completed when KYAMS participants were aged 6-12 years. Ordinal logistic regression was used to test the association between self-reported sun-behaviours and corresponding parent-reported data. We found slight agreement between self-reported and parent-reported data for all sun-behaviour measures except hat use at 12 years. KYAMS recall of time in sun at 8-12 years was not associated with Kidskin Study parent-reported responses after adjustment for current time in sun. Recall of higher hat and sunscreen use was associated with higher parent-reported hat and sunscreen use (OR[hat] = 1.37, 95% CI: 1.16, 1.62; OR[sunscreen] = 1.23, 95% CI: 1.03, 1.48). However, KYAMS self-reported data were unable to predict corresponding parent-reported responses. Group data from retrospective recall of sun-related behaviours may be of limited value in studying the relationship between sun exposure and health outcomes; however, individual data are likely of little use.

Background: UV filters should be determined a strict toxicological safety prior to approval. Homosalate (HMS) is one of the most widely used organic UV filter. HMS accumulates in aquatic biota ecosystems and humans through the food chain; therefore, it is important to consider the effects on health and know its mechanisms of action., Aims: The study aimed to evaluate the cytotoxic and genotoxic effects of HMS in MCF-7 cell line., Methods: Cell viability was examined by the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) and cell membrane integrity by the lactate dehydrogenase release assays (LDH), and genotoxicity by using the micronucleus test at 250, 500, 750, 1000, 1500, and 2000 µM concentrations with the human breast cell line MCF-7., Results: Homosalate affected the cell viability dose-dependently at a concentrations of above 1000 µM. Micronucleus formation was significantly induced at 750 and 1000 µM within 24 hours due to an increase in cytostatic effect, the cell viability of HMS decreased to 57% at a concentration of 2000 µM, and a sufficient number of binucleated cells could not be obtained to count. Homosalate was also clastogenic when the cells were incubated at cytotoxic concentrations., Conclusion: These results suggest that homosalate can be considered as a cytotoxic and genotoxic substance., (© 2019 Wiley Periodicals, Inc.)

Background: Liver transplantation (LT) is the best treatment in selected patients with hepatocellular carcinoma (HCC). Morphologic criteria alone are not sufficient to predict survival. In this study, we investigated the clinical, biochemical, and pathologic factors affecting survival in patients who underwent LT due to HCC., Methods: Between October 2011 and January 2018, 165 of 749 LT for HCC cases performed at the Memorial Atasehir Hospital were evaluated retrospectively. Survival, demographic characteristics and etiology, preoperative alpha-fetoprotein (AFP) level, Model for End-Stage Liver Disease (MELD) score, prognostic staging, and morphologic and histologic properties were evaluated., Results: One hundred and thirty-nine cases of 165 were living donor liver transplantation (LDLT). The mean age was 57.7 ± 7.3 years, the mean follow-up period was 27.8 ± 20 months, and 41 patients (24%) died before follow-up. Recurrence of HCC was detected in 23 (14%) cases. Overall survival was 85%, 71%, and 64% for 1, 3, and 5 years, respectively. In terms of 1-, 3-, and 5-year survival within vs beyond Milan criteria was 90%, 80%, and 76% vs 75%, 66%, and 44%, respectively. In the University of California San Francisco criteria, it was 86%, 76%, and 70% vs 76%, 60%, and 30% compared with 1-, 3-, and 5-year survival. While histopathological poor differentiation and AFP elevation affected the course negatively. Good differentiation did not have a significant effect on survival. It was determined that poor differentiation, lymphovascular invasion, and an increased number of nodules significantly affected survival in both within and beyond cases., Conclusion: A transplant decision is controversial in patients with HCC with other than previously defined morphologic criteria. In these cases, AFP level and histologic differentiation determine survival. The results were not satisfactory in both high and/or poorly differentiated cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose : To consider the effect of including past sun exposure in estimating heritability and familial correlation of myopia-related traits. Methods : We calculate familial correlation and heritability of anterior chamber depth (ACD), axial length (AL), corneal curvature (CC), and spherical equivalent (SphE), with or without past sun exposure as a covariate, in a large number of unrelated nuclear families from the Raine Study (parents: Gen1, offspring: Gen2) residing in Perth, Australia, a city with a high amount of daily sunlight. Past sun exposure was objectively measured using conjunctival ultraviolet autofluorescence (CUVAF) photography. Results : When sun exposure was not included in the analysis, both familial correlation (correlation±SE; ACD: 0.308 ± 0.065, AL: 0.374 ± 0.061, CC: 0.436 ± 0.063, SphE: 0.281 ± 0.070) and heritability (ACD: 0.606 ± 0.104, AL: 0.623 ± 0.098, CC: 0.793 ± 0.079, SphE: 0.591 ± 0.106) were significant for all traits (all P < .001). However, there was no significant change in both familial correlation and heritability estimates when sun exposure was included as an additional covariate. Conclusions : Past sun exposure does not affect the estimation of the additive genetic component in myopia-related traits.

Purpose: Obstructive sleep apnea (OSA) is linked to increased glaucoma risk in middle-aged and older adults. However, little is known about associations between OSA and glaucoma-related optic disc parameters in young adults. We explored associations between overnight polysomnography-derived measures of OSA and the optic disc in young adults., Design: Cross-sectional cohort study., Participants: Eight hundred forty-eight adults 19 to 22 years of age., Methods: Participants underwent an ophthalmic examination that included OCT imaging of the optic disc and measurements of intraocular pressure, axial length, and refractive error. Participants then underwent an overnight polysomnography study that obtained measurements of apnea-hypopnea index (AHI), peripheral oxygen saturation level, and number of cortical arousals from sleep. Based on the AHI results, participants were grouped into no OSA (AHI < 5 events/hour), mild OSA (AHI ≥ 5 and <15 events/hour), moderate OSA (AHI ≥ 15 and <30 events/hour), or severe OSA (AHI ≥ 30 events/hour)., Main Outcome Measures: Neuroretinal rim area, horizontal and vertical widths, and peripapillary retinal nerve fiber layer (RNFL) thickness., Results: The median AHI result across the study cohort was 2.2 events per hour (interquartile range, 1.0-4.4 events/hour). Based on the AHI results, 178 participants (21.0%) demonstrated OSA: 150 with mild OSA, 26 with moderate OSA, and 2 with severe OSA. In the unadjusted analyses, participants with OSA on average showed thinner peripapillary RNFL at the inferotemporal (P = 0.026) and superotemporal (P = 0.008) segments compared with those without OSA. Additionally, higher AHI results were associated with thinner RNFL superotemporally (P = 0.007). These findings remained significant after adjusting for gender, body mass index, ethnicity, and potential ocular confounders. There were no significant differences in optic disc measures between groups of OSA severity., Conclusions: Obstructive sleep apnea may be associated with preclinical thinning of the peripapillary RNFL in young adults. This suggests that an increased glaucoma risk already may be present in individuals with OSA since young adulthood. Long-term follow-up of this cohort will allow further optic disc changes in relationship to polysomnography parameters to be documented and associations with future glaucoma diagnosis to be explored., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Random flaps are frequently used in the practice of reconstructive surgery. The aim of this experimental study was to investigate the effects of Allium cepa on random flap survival in rats. Fourteen Wistar rats were used for this experimental study. The subjects were divided into experiment and control groups. Rats in the experiment group received daily injections of A. cepa extract for 7 d before the elevation of the flaps. Following the treatment period, elevation and reinsertion of the dorsal flaps were performed. Necrotic and total flaps areas were marked and calculated 7 d after the flap elevation. Histological examinations and microangiography were performed to evaluate the results. The mean value of the proportion of necrotic flap areas to the total flap area was 25.06 and 50.6% in the A. cepa and control group, respectively ( p  = .0079). In the histological examination, number of vessels identified in the dermis were 23.75 ± 0.7 and 33.75 ± 9 in the A. cepa and control group, respectively ( p  = .7457). In angiographic images, vessels formations were more noticeable in the A. cepa group. We conclude that preoperative subcutaneous A. cepa injection increases dorsal flap survival in rats.

Background: Immediate breast reconstruction in 1 stage using permanent implants is gaining popularity and can be performed with or without the use of acellular dermal matrices. This study aimed to investigate the results of breast implants placed submuscularly without acellular dermal matrix and assess the factors affecting surgical complications., Methods: From November 2009 to March 2018, 138 patients underwent immediate breast reconstruction with permanent submuscular implants after concomitant skin-sparing or nipple-sparing mastectomies in a single institution. All implants were covered with sufficient soft tissue under a submuscular pocket., Results: One hundred thirty-eight patients were enrolled, and a total of 196 breasts were operated. The average age and body mass index (BMI) of the patients were 44.9 ± 8.8 years and 23.7 ± 3.6 kg/m, respectively. The majority of the mastectomies were therapeutic (81%). The average volume of implants was 389 ± 89 mL, and the mean follow-up was 33 months. The overall complication rate was 17% (n = 23), with skin necrosis being the most common complication followed by infections. Having a BMI equal to or greater than 25 kg/m was found to be a statistically significant predictor for overall complications (P = 0.002), whereas smoking history, age, and implant volume were not statistically significant., Conclusions: Immediate breast reconstruction in 1 stage using permanent implants can be performed with acceptable complication rates and cosmetic outcomes. Our study demonstrated that high BMI is a risk factor for overall complications. With proper patient selection and surgical technique, implants could be completely covered under a submuscular pocket.

Background: The umbilicus is an indicative aesthetic component of the abdomen. Many umbilicoplasty techniques have been defined and the most commonly used method is the round incision technique. In this paper, we present a new umbilicoplasty technique involving the use of a three-armed star flap and compare it with the round technique. Methods: Forty-eight female patients who underwent umbilicoplasty during abdominoplasty and free deep inferior epigastric perforator flap (DIEP) procedures between February 2011 and December 2016 were included in the study. Twenty patients had round umbilicoplasty, whereas in the remaining 28 patients the three armed star flap technique was used. Aesthetic outcomes of both techniques were evaluated by a questionnaire which was completed by the patients and two independent surgeons. Results: The mean follow-up period was 22 months. Hypertrophic scarring was seen in one patient with the three armed star flap technique and in two patients with the round technique and a cicatricial ring formation occurred in one patient with the round technique. The patient and surgeon questionnaire scores were significantly higher in the 3-armed star flap group. ( p  < .05) Conclusion: In this study, round umbilicoplasty technique has been compared with the three armed star flap technique. Patient satisfaction surveys and evaluation by two independent surgeons revealed better cosmetic results with the new technique. We believe that this new technique could be preferred over the round technique since it prevents stenosis, circular scar contraction and provides a natural contour between the umbilicus and abdomen.

One of the simplest form of surgical delay can be performed by placing an incision around the flap without undermining, prior to flap elevation. In this study, we have compared the efficiency of different patterns of skin incision to improve flap survival. Twenty-eight animals were used in four groups. Incisional delay was performed prior to flap elevation in the three experiment groups. Complete incision of the three flap edges was performed in the all experiment groups with the exception of an intact skin section on the middle 1/3rd of the bilateral edges in group 1 (bilateral skin edge preserved delay: BSEPD), of a unilateral edge in group 2 (unilateral skin edge preserved delay: USEPD) and of the superior edge in group 3 (superior skin edge preserved delay: SSEPD) without any undermining. Two weeks following the delay procedure, dorsal skin flaps were raised and reinserted back to their place. The results were evaluated with the measurement of necrotic flap area, microangiographic imaging and histological evaluation. The mean percentage of necrotic flap area to whole flap area was 16.94%, 7.54%, 23.34% and 50.6% in the BSEPD, USEPD, SSEPD and control groups, respectively. In selected microangiographic images, vessels were more prominent in the delay groups. The results of the study indicate that three sided incision with an intact skin on the superior edge is not effective in providing a sufficient delay and flap survival improvement when compared to incisions with intact skin on the unilateral and bilateral edges.

Background: Middle crura support deficiency and short middle crura can usually cause insufficient definition and projection of the tip and can sometimes result in a flat tip. The aim of this study was to investigate the effectiveness of a new technique involving a tip reinforcement flap to strengthen the middle crura and to achieve a well-projected and defined tip., Methods: Twenty-nine patients who underwent primary open-approach rhinoplasty that included the use of tip reinforcement flaps were included in the study. Cartilage flaps that had been created from the excess cephalic portion of the lateral crura were prepared as medial crura-based cartilaginous flaps., Results: There were 29 patients (17 women, 12 men) aged 18 to 44 years (mean age, 31 years). Follow-up time ranged between 3 and 25 months (mean, 21 months). Preoperative and postoperative average of nasal tip length was 10.84 (±1.07) mm and 14.32 (±2.34) mm, respectively (P = 0.0214). Preoperative and postoperative average of nasolabial angle was 97.42° (±9.84°) and 107.99° (±12.16°), respectively (P = 0.0344). Preoperative and postoperative average of nasal projection ratio was 0.53 (±0.04) and 0.57 (±0.03), respectively (P = 0.4347). The tip reinforcement flap technique provided strengthening and extra support for the middle crura and increased definition, projection, and stability to the domal area., Conclusions: The tip reinforcement flap technique offers advantages for tip plasty in those cases with middle crural deficiency, short middle crura, and middle crural weakness. The technique also provides an additional projection, stabilization, and definition to the nasal tip while reducing lateral crural cephalic excess. This technique improves nostril-lobular disproportion and has the advantage of hiding extra support grafted into the folded flap. Complications such as graft visibility, malposition, and asymmetry, which may occur with the use of classic tip grafts, can be eliminated with the tip reinforcement flap technique.

Background and objectives: Abdominoplasty is one of the most commonly performed cosmetic procedures. The excess skin in the conventional abdominoplasty is transversely excised and a single horizontal scar is formed. The mini inverted t-scar abdominoplasty is a modification of the "Fleur-de-lis" technique and involves the use of a small vertical incision in comparison to the long vertical incision. The aim of this technique is to lower the position of the final abdominal scar instead of addressing the horizontal laxity. In this study, we have compared the aesthetic satisfaction, width and the position of the scar with conventional abdominoplasty and mini inverted t-scar abdominoplasty. Materials and Methods: Thirty patients undergoing abdominoplasty and breast reconstruction with transverse rectus abdominis flap (TRAM) and deep inferior epigastric flap (DIEP) were included in the study. In 15 patients, abdominal closure with the conventional transverse scar was performed. In the remaining 15 patients, closure with a mini inverted t-scar was performed. Scar width, scar height and satisfaction scores were evaluated in both groups. Results: Scar widths, scar heights and patients' and as well as surgeons' satisfaction scores were better in the mini inverted t-scar group than the conventional group. Conclusions: The visibility of the vertical scar alone should not be a reason to avoid mini inverse t-scar abdominoplasty. Mini inverted t-scar can be an option to achieve a better hidden high-quality scar., Competing Interests: The authors declare no conflicts of interest.

Importance: Excessive ocular sun exposure is linked to various eye pathologies. Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting sun-related conjunctival damage; however, the custom-built camera system required is not readily available., Background: We investigated whether blue laser autofluorescence (BAF) on a commonly used confocal scanning laser ophthalmoscope (cSLO) can be utilized to measure CUVAF area., Design: Cross-sectional evaluation of a diagnostic technology at a medical research institute., Participants: Sixty-four participants recruited from three on-going observational eye studies in Western Australia., Methods: All participants had four images, two of each eye, captured using the CUVAF camera and BAF on the same day. Participants with pterygium or poor quality images were excluded from the analysis. Two graders measured CUVAF area in each image twice. CUVAF area measured by BAF was then compared to measurements determined with the conventional camera system., Main Outcome Measures: CUVAF area., Results: After exclusions, 50 participants' images were analysed. Intra- and inter-observer repeatability were similar between the two systems. When comparing CUVAF area measured by BAF to the camera measurement, grader 1 had a mean difference of +1.00 mm 2 , with 95% limits of agreement -5.75 to 7.77 mm 2 . Grader 2 had a mean difference of +0.21mm 2 , with 95% limits of agreement -7.22 to 7.64 mm 2 ., Conclusions and Relevance: BAF on a commercially available cSLO is a valid method for measuring CUVAF area. This finding provides broader opportunity for identifying, monitoring and educating patients with sun-exposure-related ocular conditions and for researching the ocular impacts of sun exposure., (© 2018 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: It has been suggested that female sex steroids have neuroprotective properties that may reduce risk of glaucoma in premenopausal women. In this study, we explored the associations of optic disc measures with female reproductive factors in a population of young women., Design: Cohort study., Methods: Young women (n = 494; age range, 18-22 years) were recruited as part of the Western Australian Pregnancy Cohort (Raine) Study. Information on age at menarche, parity, and use of hormonal contraceptives were obtained from questionnaires. Participants underwent an eye examination, including spectral-domain optical coherence tomography imaging, to obtain optic disc parameters., Results: Women who had given birth at least once (parous women; n = 10) had larger vertical neuroretinal rim widths (P < 0.001) than nulliparous women (n = 484) after correcting for use of hormonal contraceptives, intraocular pressure, refractive error, and family history of glaucoma. Furthermore, vertical and horizontal cup-to-disc ratios, which are inherently related to neuroretinal rim width, were found to be smaller among parous women compared with nulliparous women (both P < 0.001). Age at menarche and use of hormonal contraceptives were not significantly associated with any optic disc parameters., Conclusions: We found limited evidence that female reproductive factors were related with optic disc parameters during young adulthood. The association between parity and optic disc parameter, though significant, should be further investigated given the small number of parous women in the current sample. Future follow-ups of this cohort will allow us to explore for any associations of these factors with optic disc parameters and glaucoma risk at an older age., (Copyright 2019 Asia-Pacific Academy of Ophthalmology.)

Metastasis via the lymphatic vasculature is an important step in cancer progression. The formation of new lymphatic vessels (lymphangiogenesis), or remodeling of existing lymphatics, is thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis. While chemokines are known to provide directional navigation for migrating immune cells, their role in mediating LEC migration during tumor-associated lymphangiogenesis is not well defined. Here, we undertook gene profiling studies to identify chemokine-chemokine receptor pairs that are involved in tumor lymphangiogenesis associated with lymph node metastasis. CCL27 and CCL28 were expressed in tumor cells with metastatic potential, while their cognate receptor, CCR10, was expressed by LECs and upregulated by the lymphangiogenic growth factor VEGFD and the proinflammatory cytokine TNFα. Migration assays demonstrated that LECs are attracted to both CCL27 and CCL28 in a CCR10-dependent manner, while abnormal lymphatic vessel patterning in CCR10-deficient mice confirmed the significant role of CCR10 in lymphatic patterning. In vivo analyses showed that LECs are recruited to a CCL27 or CCL28 source, while VEGFD was required in combination with these chemokines to enable formation of coherent lymphatic vessels. Moreover, tumor xenograft experiments demonstrated that even though CCL27 expression by tumors enhanced LEC recruitment, the ability to metastasize was dependent on the expression of VEGFD. These studies demonstrate that CCL27 and CCL28 signaling through CCR10 may cooperate with inflammatory mediators and VEGFD during tumor lymphangiogenesis. SIGNIFICANCE: The study shows that the remodeling of lymphatic vessels in cancer is influenced by CCL27 and CCL28 chemokines, which may provide a future target to modulate metastatic spread., (©2019 American Association for Cancer Research.)

Objectives: Although malignant melanoma accounts for 3% of skin cancers, it is responsible for 75% of deaths associated with skin cancer. In our study, all melanoma cases diagnosed and treated at our clinic were retrospectively reviewed, and the cases of unknown primary origin among them were examined in detail in terms of diagnosis and treatment., Methods: The patients with malignant melanoma treated at the inpatient services of our clinic between January 1991 and April 2017 were retrospectively screened in the records. These patients were evaluated for age, sex, tumor type, Breslow depth, metastasis, and treatment. Among these patients, four cases of unknown primary origin were examined in detail., Results: During January 1991 and April 2017, 173 patients received inpatient care for malignant melanoma at our clinic. As regards to the melanoma subtypes, nodular type in 45 patients, acral lentiginous type in 43 patients, superficial spreading type in 63 patients, lentigo maligna melanoma in 15 patients, subungual type in 7 patients, and either unidentified melanoma or other subtypes in 10 patients were identified., Conclusion: The ideal treatment of a patient with melanoma is multidisciplinary, with plastic surgery having a central role., Competing Interests: Conflict of Interest: None declared., (Copyright: © 2019 by The Medical Bulletin of Sisli Etfal Hospital.)

Purpose: In Bornholm eye disease, a defect in the splicing of transcripts from a variant OPN1LW opsin gene leads to a depletion in spliced transcript levels and, consequently, a reduction in photopigment in photoreceptors expressing the variant gene., Methods: Myopic and age-matched control subjects were drawn from the Western Australian Pregnancy Cohort (Raine) Study and the Norfolk Island Eye Study groups. The OPN1LW opsin gene was amplified using long-range PCR methodology and was fully sequenced. Expression of variant opsins was evaluated using quantitative PCR (qPCR). RNA secondary structure changes arising from identified variants were predicted by modeling., Results: Forty-two nucleotide sites were found to vary across the 111 subjects studied. Of these, 15 had not been previously reported, with three present only in myopic individuals. Expression of these variants in transfected human embryonic kidney (HEK293T) cells demonstrated that splicing efficiencies were not affected. However, gene transcripts from two of the three variants were significantly depleted. RNA secondary structure modeling predicted that these single nucleotide changes could affect RNA stability., Conclusions: None of the variants identified in myopic individuals appeared to alter the efficiency of transcript splicing. However, two resulted in a significant reduction in the number of spliced and unspliced transcripts, indicating an overall reduction in steady-state transcript stability. Such a change would be expected to result in a reduced amount of photopigment, and this may be a contributing factor in the development of myopia.

The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.

Random skin flaps are essential tools in reconstructive surgery. In this study, we investigated the effect of subdermal nitrous oxide (N 2 O) application on random flap survival. In this experimental study, we used 21 female rats in three groups. In the N 2 O and air groups, gases were administrated under the proposed dorsal flap areas daily for seven days. Following the treatment period, flaps were raised and inserted back into their place from the dorsal skin. In the control group, the flaps were elevated and inserted back to their place without any pretreatment. Calculation of necrotic flap areas, histological examination and microangiography was performed to evaluate the results 7 days after the flap surgery. The average of necrotic flap area in the N 2 O, air and control group was 13.45%, 37.67% and 46.43%, respectively. (N 2 O vs air p = .044; N 2 O vs control p = .003). The average number of capillary formations identified in the histological analysis was 7.0 ± 1.58, 3.75 ± 2.36 and 4.4 ± 0.54 in the N 2 O, air and control group, respectively. (N 2 O vs air p = .017; N 2 O vs control p = .037). The average number of capillary structures identified in the angiography images were 6.3 ± 1.52, 1.6 ± 1.15 and 1.3 ± 0.57 in the N 2 O, air and control group, respectively. (N 2 O vs air p = .04; N 2 O vs control p = .02). We conclude that subdermal N 2 O application increases random flap survival through an increase in the skin microcirculation and could be promising for future clinical applications.

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentration and refractive error in a community-based cohort of adults aged 46 to 69 years., Methods: Residents of the City of Busselton in Western Australia born between 1946 and 1964 were invited to participate. Participants underwent cycloplegic autorefraction and completed questionnaires on education, occupational sun exposure, and physical activity. Blood samples were collected and serum frozen at -80°C. Serum 25[OH]D concentration was measured by immunoassay. Data on 25[OH]D were deseasonalized and multivariate models built to analyze the association between 25[OH]D concentration and spherical equivalent and myopia, defined as spherical equivalent <-0.50 D., Results: After exclusions, data were available for 4112 participants. Serum 25[OH]D concentration was not associated with spherical equivalent or myopia after adjustment for confounding factors (β = -0.01, 95% confidence interval [CI]: -0.03 to -0.008, P = 0.25, and odds ratio = 1.02, 95% CI: 0.99 to 1.05, P = 0.12, respectively). When participants were classified into 25[OH]D groups of lower (<50 nmol/L), medium (≥50 to <75 nmol/L), and upper (≥75 nmol/L), the upper group had slightly greater myopic refractive error than the medium group ( P = 0.02) but not the lower group, after adjustment for confounders., Conclusions: There was no substantial association between 25[OH]D levels and spherical equivalent or odds of myopia in this study. The association previously noted between low serum 25[OH]D level and myopia in younger Western Australians is not evident in later adulthood., Translational Relevance: This study provides further evidence suggesting that vitamin D levels are unrelated to myopia risk in adults and thus not a suitable target for myopia intervention.

The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.

Objective: To conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia., Methods: We searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated., Results: We summarised seven studies involving 25 008 individuals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=-0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p<0.0001). However, the association was not statistically significant for the <18 years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007; AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies; there was no significant association with myopia., Conclusions: Lower 25(OH)D is associated with increased risk of myopia; the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Osteotomy is a crucial step in rhinoplasty, which can have a significant impact on the outcome. In addition to previous percutaneous (external perforating) and endonasal (internal) approaches, piezosurgery has been used in rhinoplasty practice since 2007. This experimental model was planned to compare the three osteotomy techniques., Materials and Methods: This study was performed on a caprine skull osteotomy model. Three groups were created from 12 animals, namely, endonasal continuous, external perforating, and piezosurgery groups. All the groups were evaluated for bone gaps, comminuted fractures, and nasal mucosa damage., Results: There were no comminuted fractures and mucosal defects in any of the samples in the piezo osteotomy group. The average amount of bone gap at the osteotomy site and the nasal mucosa damage was lower in the piezo group than in the other groups. The time required for the osteotomy was shorter in the endonasal group, similar to that in the external and piezo groups., Conclusion: New techniques are constantly being developed to achieve better results in rhinoplasty. As a natural consequence to technological developments, new devices are being introduced to rhinoplasty practice. Piezo is one such device. We have found that piezo osteotomy has resulted in lower amounts of nasal mucosal damage and comminuted fractures. We believe that piezo can safely be used in rhinoplasty practice until newer and more reliable technologies are being developed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.

Purpose: To determine whether mitochondrial DNA haplogroups or rare variants associate with primary open-angle glaucoma in subjects of European descent., Methods: A case-control comparison of age- and sex-matched cohorts of 90 primary open-angle glaucoma patients and 95 population controls. Full mitochondrial DNA sequences from peripheral blood were generated by next-generation sequencing and compared to the revised Cambridge Reference Sequence to define mitochondrial haplogroups and variants., Results: Most subjects were of the major European haplogroups H, J, K, U, and T. Logistic regression analysis showed haplogroup U to be significantly underrepresented in male primary open-angle glaucoma subjects (odds ratio 0.25; 95% confidence interval [CI] 0.09-0.67; P = 0.007; Bonferroni multiple testing P = 0.022). Variants in the mitochondrial DNA gene MT-ND2 were overrepresented in the control group (P = 0.005; Bonferroni multiple testing correction P = 0.015)., Conclusions: Mitochondrial DNA ancestral lineages modulate the risk for primary open-angle glaucoma in populations of European descent. Haplogroup U and rare variants in the mitochondrial DNA-encoded MT-ND2 gene may be protective against primary open-angle glaucoma. Larger studies are warranted to explore haplogroup associations with disease risk in different ethnic groups and define biomarkers of primary open-angle glaucoma endophenotypes to target therapeutic strategies.

Background: The goals of tracheostomy scar revision are filling of the depressed area, providing easy sliding of skin over the trachea. There are various techniques described to correct this situation. In this article, a modification of split sternocleidomastoid (SCM) muscle flap used in the correction of posttracheostomy defects is described., Methods: Thirteen patients who had depressed scars after tracheostomy are included in this study. The mean patient age was 44 years (range, 27-56 years). All patients who suffered from tracheal tug, dysphagia, and bad appearance are included in the study. The area with the depressed scar is de-epithelialized after incising around the depression. Bilateral SCM muscles are split in the coronal plane toward superior half of the muscle while leaving the posterior part of the muscle attached to the bone. After elevation, both SCM muscle flaps are overlapped in the midline., Results: The mean follow-up period of the patients was 11 months (range, 5-20 months). Tracheal tug and dysphagia complaints were resolved in all patients. The depressed area due to the scar was either reduced or completely recovered in all the patients. Apart from 1 hematoma case, none of the early or late complications such as infection, wound dehiscence, skin necrosis, seroma, recurrence, or neck contracture was seen., Conclusions: We think that this technique, which gives functionally and aesthetically satisfying results, can be used safely in depressed scars formed after tracheostomy and treatment of functional impairment due to this procedure.

Aneurysmal fibrous histiocytoma (AFH) is a type of fibrohistiocytic tumour. We present a case of a patient who presented with a skin papule on the thigh region. Histopathological examination following total excision of the lesion revealed an AFH. No sign of recurrence was present 6 months after surgery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To identify genetic variants conferring susceptibility to esotropia. Esotropia is the most common form of comitant strabismus, has its highest incidence in European ancestry populations, and is believed to be inherited as a complex trait., Methods: White European American discovery cohorts with nonaccommodative (826 cases and 2991 controls) or accommodative (224 cases and 749 controls) esotropia were investigated. White European Australian and United Kingdom cohorts with nonaccommodative (689 cases and 1448 controls) or accommodative (66 cases and 264 controls) esotropia were tested for replication. We performed a genome-wide case-control association study using a mixed linear additive model. Meta-analyses of discovery and replication cohorts were then conducted., Results: A significant association with nonaccommodative esotropia was discovered (odds ratio [OR] = 1.41, P = 2.84 × 10-09) and replicated (OR = 1.23, P = 0.01) at rs2244352 [T] located within intron 1 of the WRB (tryptophan rich basic protein) gene on chromosome 21 (meta-analysis OR = 1.33, P = 9.58 × 10-11). This single nucleotide polymorphism (SNP) is differentially methylated, and there is a statistically significant skew toward paternal inheritance in the discovery cohort. Meta-analysis of the accommodative discovery and replication cohorts identified an association with rs912759 [T] (OR = 0.59, P = 1.89 × 10-08), an intergenic SNP on chromosome 1p31.1., Conclusions: This is the first genome-wide association study (GWAS) to identify significant associations in esotropia and suggests a parent-of-origin effect. Additional cohorts will permit replication and extension of these findings. Future studies of rs2244352 and WRB should provide insight into pathophysiological mechanisms underlying comitant strabismus.

Introduction: Burn healing is a complicated process and very few treatments can positively alter its effects. The aim of this study was to investigate the effects Salvia miltiorrhiza (SM -Danshen), a traditional Chinese medicine, on burn wound healing., Material and Methods: Twenty rats were included in this study and divided into two groups. 3 × 2 cm wide burn areas were created in the dorsal skin of all the animals with thermal contact. Intraoral 1 ml/day saline and 1 g/kg/day SM were given in control and experiment groups, respectively. Fourteen days following the burn injury burn zones were evaluated with indocyanine green-SPY imaging device, and multiple samples were collected for histopathological evaluation. Standard photographs were taken for the evaluation of necrotic skin areas., Results: Neovascularization was increased in the SM group when compared with the control group (p = 0.0406). SPY studies revealed a meaningful increase in the tissue perfusion in the SM group (p = 0.0286). The average amount of necrotic area in the control and experiment group on the postoperative 14th day was 71.6% (±16.51) and 42.5% (±10.64) respectively (p = 0.0002)., Conclusion: Our study shows that SM can decrease the amount of necrosis in burn wounds by increasing tissue perfusion and neovascularization.

Background: Breast reconstruction with a Becker-type expander is a common technique following mastectomy. However, inconsistency remains in the literature regarding risk factors for the survival of a Becker-type expander following immediate breast reconstruction. This study's purpose is to investigate possible risk factors for the Becker-type expander survival and to evaluate the complications related to expander removal following immediate breast reconstruction., Methods: We performed a retrospective chart review of consecutive women who underwent a mastectomy followed by immediate breast reconstruction with a Becker-type expander from November 2010 to November 2016. Electronic medical records were analyzed retrospectively for demographic, clinical, operative characteristics, and outcomes. Univariate Cox regression analysis was performed to determine the risk factors for the survival of the Becker-type expander following immediate breast reconstruction., Results: A total of 74 Becker-type expanders were used in 72 patients who underwent immediate breast reconstruction. The patients' ages ranged from 27 to 71 years, with a mean ± standard deviation age of 44.6 ± 9.1 years. The most frequent complication was capsular contracture which occurred in 25 breasts (33.8%) followed by mastectomy skin flap necrosis in 6 breasts (8.1%), seroma in 4 breasts (5.4%), nipple-areolar complex necrosis in 4 breasts (5.4%), hematoma in 3 breasts (4.1%), and infection in 2 breasts (2.7%). The mean intraoperative expander fill volume (109.6 ± 66.9 cc [p = 0.039]) and mean total volume (386.5 ± 94.7 cc [p = 0.034]) were both significantly lower for patients with capsular contracture compared with those without capsular contracture. In patients with partial NAC necrosis, the mean mastectomy specimen volume (737.5 ± 242.8 cc) was significantly higher compared with patients without partial NAC necrosis (489.8 ± 219.0 cc; p = 0.027). A univariate Cox regression analysis showed that smoking and neoadjuvant therapy were significantly associated with expander removal (p = 0.023 and p = 0.006, respectively)., Conclusion: The total volume of the expander and intraoperative fill volume of the expander appear to be predictive factors in the development of capsular contracture. However, there is no statistically significant association between radiotherapy and capsular contracture or expander survival in contrast with other published reports. Our findings reveal that the main risk factors for the survival of Becker-type expanders following immediate breast reconstruction are smoking and neoadjuvant therapy. To our knowledge, this is the first study to evaluate the most likely risk factors associated with Becker-type expander survival in immediate breast reconstruction., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10 -5 ) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations. These results confirm the polygenic nature of complex phenotypes and improve our understanding of melanin pigment metabolism in humans.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

Purpose: To identify genes and genetic markers associated with corneal astigmatism., Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression., Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( PDGFRA ) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10 -9 . No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 ( CLDN7 ), acid phosphatase 2, lysosomal ( ACP2 ), and TNF alpha-induced protein 8 like 3 ( TNFAIP8L3 )., Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7 , ACP2 , and TNFAIP8L3 , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

Background: Breast reconstruction with implants is a real challenge in patients with large breast volume. Skin-reducing inverted-T mastectomy is the best solution for these patients. Delayed wound healing or necrosis at the T-junction area can be seen in this procedure, although it may also lead to severe conditions such as the exposure and loss of implant. In this article, the use of local pedicled flap for the management of these situations was discussed., Methods: Between April 2010 and July 2015, 54 patients underwent breast reconstruction by inverted-T skin-reducing mastectomy and immediate implant-based breast reconstruction at our clinic. During the postoperative follow-up period, necrosis at the T-junction area was observed in 8 patients. All the patients received proper wound care, and the necrosis was surgically debrided. The defect was closed with Limberg-like rectangular flap., Results: The mean age was 45.2 (range, 33-54) years. The mean body mass index was 25.57 ± 6.53 (range, 21.2-35.2) kg/m. The mean follow-up was 10.9 (range, 4-19) months. Two patients had implant exposure at the defect site after the debridement. There was no implant loss in any of the patients., Conclusions: The Limberg-like rectangular flap can be used as a salvage option in complicated skin-reducing mastectomies and can be considered as a safe and effective method because of its easy-to-use nature, low cost, and no need for microsurgery experience.

Introduction: Excessive and insufficient sun exposure during childhood have been linked to serious diseases in later life; for example, insufficient sun exposure during childhood may increase the risk of developing myopia. The Kidskin-Young Adult Myopia Study (K-YAMS) is a follow-up of participants in the Kidskin Study, a non-randomised controlled trial that evaluated the effect of a 4-year educational intervention on sun-protection behaviours among primary school children in the late 1990s. Children who received the Kidskin intervention had lower levels of sun exposure compared with peers in the control group after 2 and 4 years of the intervention, but this was not maintained 2  years after the intervention had ceased. Thus, a follow-up of Kidskin Study participants provides a novel opportunity to investigate the associations between a childhood sun-exposure intervention and potentially related conditions in adulthood., Methods and Analysis: The K-YAMS contacts Kidskin Study participants and invites them to participate using a variety of methods, such as prior contact details, the Australian Electoral Roll and social media. Self-reported and objective measures of sun-exposure and sun-protection behaviours are collected as well as a number of eye measurements including cycloplegic autorefraction and ocular biometry. Data will be analysed to investigate a possible association between myopic refractive error and Kidskin intervention group or measured sun exposure., Ethics and Dissemination: The K-YAMS is approved by the Human Research Ethics Committee of the University of Western Australia (RA/4/1/6807). Findings will be disseminated via scientific journals and conferences., Trial Registration Number: ACTRN12616000812392; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim of the Study: Postmastectomy reconstructive surgery for cosmetic satisfaction of patients is rapidly increasing. Postoperative complications such as infection, capsular contracture, implant loss are more common in patients who receive adjuvant radiotherapy (RT) than those who do not. Satisfaction levels in patients is still a controversial issue. Therefore, we wanted to investigate our patient population for the effects of RT and planned a study evaluating the satisfaction rates of our patients who received implants., Material and Methods: Seventy five breast cancer patients who went through mastectomy and went through reconstruction using expanders or silicone implants were surveyed. Complication and cosmetic satisfaction rates were separately compared between irradiated and nonirradiated implants. Responses of 46 patients who answered the survey were analyzed using χ 2 test and Mann Whitney U test. p < 0.05 was considered statistically significant., Results: Thirty-one of the patients received adjuvant RT and 15 did not receive RT (NRT). There was no difference between the RT and NRT groups in the terms of touch, size, shape of silicones, pain and satisfaction level in look of clothing. Only satisfaction in symmetry was significantly lower in the RT group than in the NRT group ( p = 0.02). Additionally, patients receiving chemotherapy were less satisfied with silicone size than those who did not ( p = 0.02)., Conclusion: We did not find negative effects, other than symmetry, of adjuvant radiotherapy in breast cancer patients who underwent reconstructive surgery in terms of cosmetic satisfaction., Competing Interests: The authors declare no conflict of interest.

Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia., Methods: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH)D concentration as instrumental variables (IV). We estimated the effect of 25(OH)D on myopia level using a Wald-type ratio estimator based on the effect estimates from the CREAM GWAS., Results: Using the combined effect attributed to the four SNPs, the estimate for the effect of 25(OH)D on refractive error was -0.02 [95% confidence interval (CI) -0.09, 0.04] dioptres (D) per 10 nmol/l increase in 25(OH)D concentration in Caucasians and 0.01 (95% CI -0.17, 0.19) D per 10 nmol/l increase in Asians., Conclusions: The tight confidence intervals on our estimates suggest the true contribution of vitamin D levels to degree of myopia is very small and indistinguishable from zero. Previous findings from observational studies linking vitamin D levels to myopia were likely attributable to the effects of confounding by time spent outdoors., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

A surgical case, in which inferior dermal flap was used to cover a tissue expander for breast reconstruction, is reported. In spite of the skin necrosis on the seventh postoperative day, flap coverage successfully protected the tissue expander from exposition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)