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Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

Background Age-related cataract is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation (UVR), and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Further research into the genetic basis of cataracts could provide valuable insights into the disease's etiology and lead to a better understanding of biological mechanisms that are associated with its development. Methods This study presents the largest genome-wide association study of cataracts to date, using data from 127,985 cases and 837,371 controls. We performed gene enrichment analysis to identify genes and biological pathways associated with cataracts. We integrated our results with gene expression reference datasets to identify genetic variants modifying risk for cataracts through changes in the expression of specific genes. We further explored drug-gene interactions to better understand the potential impact of pharmacological interventions on cataract development. Finally, we explored whether a causal relationship underlies the known comorbidity between type 1 diabetes and cataracts using a mendelian randomization framework, and the association between UV exposure and cataract risk in adults using a polygenic risk scoring approach. Findings Our study identified 85 independent genome-wide significant loci, 37 of which are novel. Gene-based association tests identified 126 genes associated with cataracts, hinting at a potential relationship between negative regulation of lipid biosynthesis and the development of cataracts. Four of the genes identified GNL3, JAG1, METTL21A, and CREB1 are involved in drug-gene interactions. Moreover, Mendelian Randomisation analysis identified a putative causal relationship between genetic predisposition to type 1 diabetes and an increased risk of cataracts. Lastly, we found evidence indicating that early-life exposure to UVR may have an impact on the later development of cataracts. Interpretation Our findings advance our understanding of the genetic basis of cataract and provide new insights into its etiology. We identified multiple genes and biological pathways associated with the condition, including associations with four genes from which drug repurposing could be proposed. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults and drug-genes interactions that has the potential of informing novel therapies.

Purpose Cross-sectional studies have variably reported that poor sleep quality may be associated with myopia in children. Longitudinal data, collected over the ages when myopia develops and progresses, could provide new insights into the sleep-myopia paradigm. This study tested the hypothesis that 12-year trajectories of sleep behaviour from childhood to adolescence is associated with myopia during young adulthood. Methods At the 5-, 8-, 10-, 14- and 17-year follow-ups of the longitudinal Raine Study, which has been following a cohort since their birth in 1989-1992, participants' parents/guardians completed the Child Behaviour Checklist questionnaire (CBCL), which collected information on their child's sleep behaviour and quality. The CBCL includes six questions measuring sleep behaviour, which parents rated as 0 = not true, 1 = somewhat/sometimes true, or 2 = very/often true. Scores were summed at each follow-up to form a composite "sleep behaviour score". Latent Class Growth Analysis (LCGA) was used to classify participants according to their 12-year trajectory of sleep behaviour. At the 20-year follow-up, an eye examination was performed which included cycloplegic autorefraction and axial length measurement. Results The LCGA identified three clusters of participants based on their trajectory of sleep behaviour: those with minimal' (43.6% of the total Raine Study sample), 'declining' (48.9%), or 'persistent' (7.5%) sleep problems. A total of 1194 participants had ophthalmic data and longitudinal sleep data available for analysis (47.2% female, 85.6% Caucasian). No significant differences were observed in regards to age, sex, ethnicity or ocular parameters between trajectory groups. Unadjusted and fully adjusted analyses demonstrated that sleep problem behaviour was not significantly associated with changes in refractive error, axial length or corneal radius. Conclusions Our findings do not support the hypothesis that there is an association between sleep behaviour and myopia. Future longitudinal studies should explore sleep trajectory data pre- and post-myopia diagnosis to confirm our results.

In utero exposure to cigarette smoke has been suggested to result in thinner retinal nerve fibre layer (RNFL). However, the potential cofounding effects of in utero alcohol exposure and passive smo...

BACKGROUND The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle-aged Australian adults over approximately a 20-year period. METHODS Two contemporary Western Australian studies (conducted in mid-late 2010s): the coastal-regional Busselton Healthy Ageing Study (BHAS) and the urban Gen1 of the Raine Study (G1RS) were compared to two earlier studies (early-mid 1990s) in Australia: the urban Blue Mountains Eye Study (BMES) and urban/regional Melbourne Visual Impairment Project (MVIP). Refractive error was measured by autorefraction, vertometry, or subjective refraction. Participants (49-70 years) of European descent without self-reported/diagnosed cataract, corneal disease, or refractive or corneal surgery were included. RESULTS After exclusions, data were available from 2217, 1760, 700, 2987 and 756 participants from BMES, urban MVIP, regional MVIP, BHAS, and G1RS, respectively. The mean age ranged from 57.1 ± 4.6 years in the G1RS to 60.1 ± 6.0 years in the BMES; 44-48% of participants were male. When stratified by location, the contemporary urban G1RS cohort had a higher age-standardised myopia prevalence than the urban MVIP and BMES cohorts (29.2%, 16.4%, and 23.9%, p

The prevalence of keratoconus (Belin/Ambrόsio Enhanced Ectasia Display Score ≥2.6 on Scheimpflug imaging) in a longitudinal, community cohort study from Western Australia was 3.4% (n=26/755). Keratoconus incidence over an 8-year period was 2.2% (n=15/669).

BackgroundTo test the hypothesis that 0.01% atropine eyedrops are a safe and effective myopia-control approach in Australian children.MethodsChildren (6–16 years; 49% Europeans, 18% East Asian, 22% South Asian, and 12% other/mixed ancestry) with documented myopia progression were enrolled into this single-centre randomised, parallel, double-masked, placebo-controlled trial and randomised to receive 0.01% atropine (n = 104) or placebo (n = 49) eyedrops (2:1 ratio) instilled nightly over 24 months (mean index age = 12.2 ± 2.5 and 11.2 ± 2.8 years, respectively). Outcome measures were the changes in spherical equivalent (SE) and axial length (AL) from baseline.ResultsAt 12 months, the mean SE and AL change from baseline were −0.31D (95% confidence interval [CI] = −0.39 to −0.22) and 0.16 mm (95%CI = 0.13–0.20) in the atropine group and −0.53D (95%CI = −0.66 to −0.40) and 0.25 mm (95%CI = 0.20–0.30) in the placebo group (group difference p ≤ 0.01). At 24 months, the mean SE and AL change from baseline was −0.64D (95%CI = −0.73 to −0.56) and 0.34 mm (95%CI = 0.30–0.37) in the atropine group, and −0.78D (95%CI = −0.91 to −0.65) and 0.38 mm (95%CI = 0.33–0.43) in the placebo group. Group difference at 24 months was not statistically significant (p = 0.10). At 24 months, the atropine group had reduced accommodative amplitude and pupillary light response compared to the placebo group.ConclusionsIn Australian children, 0.01% atropine eyedrops were safe, well-tolerated, and had a modest myopia-control effect, although there was an apparent decrease in efficacy between 18 and 24 months, which is likely driven by a higher dropout rate in the placebo group.

PRECIS Higher physical working capacity (PWC) at age 17 was associated with thicker peripapillary retinal nerve fiber layer (pRNFL) at age 20, suggesting a mechanistic link between cardiovascular fitness and neuroretinal integrity. PURPOSE Physical activity and cardiovascular fitness have been linked with lower odds of developing glaucoma. We tested the hypothesis that early beneficial effects of physical activity and cardiovascular fitness can be observed by measuring the pRNFL thickness in young healthy adults. METHODS The Raine Study is a longitudinal study that has followed a cohort since before their births in 1989-1992. Parent-reported physical activity was collected between 8 and 17 years, and latent class analysis was used to identify the participants' physical activity trajectories. At the 20-year follow-up (participants' mean age=20.1±0.4 y), participants' metabolic equivalent of task-minutes/week was determined using self-reported physical activity data. Participants' PWC was assessed at the 14- and 17-year follow-ups to estimate their level of cardiovascular fitness. An eye examination, which included spectral-domain optical coherence tomography imaging, was conducted at the 20-year follow-up for 1344 participants. RESULTS Parent-reported or participant-reported physical activity was not associated with pRNFL thickness. However, higher PWC at 17 years was associated with thicker pRNFL globally [by 0.3 µm; 95% confidence interval (CI)=0.2-0.6; P

Myopia typically starts and progresses during childhood, but onset and progression can occur during adulthood. The goals of this review are to summarize published data on myopia onset and progression in young adults, aged 18 to 40 years, to characterize myopia in this age group, to assess what is currently known, and to highlight the gaps in the current understanding. Specifically, the peer-reviewed literature was reviewed to: characterize the timeline and age of stabilization of juvenile-onset myopia; estimate the frequency of adult-onset myopia; evaluate the rate of myopia progression in adults, regardless of age of onset, both during the college years and later; describe the rate of axial elongation in myopic adults; identify risk factors for adult onset and progression; report myopia progression and axial elongation in adults who have undergone refractive surgery; and discuss myopia management and research study design. Adult-onset myopia is common, representing a third or more of all myopia in western populations, but less in East Asia, where onset during childhood is high. Clinically meaningful myopia progression continues in early adulthood and may average 1.00 diopters (D) between 20 and 30 years. Higher levels of myopia are associated with greater absolute risk of myopia-related ocular disease and visual impairment, and thus myopia in this age group requires ongoing management. Modalities established for myopia control in children would be options for adults, but it is difficult to predict their efficacy. The feasibility of studies of myopia control in adults is limited by the long duration required.

The purpose of this study was to explore the age-related change in choroidal thickness (ChT) and test the hypothesis that baseline ChT is predictive of refractive error change in healthy young adults.Participants underwent spectral-domain optical coherence tomography (SD-OCT) imaging and autorefraction at 20 (baseline) and 28 years old. The enhanced depth imaging mode on the SD-OCT was used to obtain images of the choroid. Scans were exported from the SD-OCT and analyzed with a custom software that automatically measures the central ChT. The longitudinal change in subfoveal ChT and association between baseline subfoveal ChT and 8-year change in refractive error (spherical equivalent) were determined using linear mixed models.In total, 395 eyes of 198 participants (44% men; 18-22 years at baseline) were included. Over 8 years, mean spherical equivalent decreased by 0.25 diopters (D) and axial length increased by 0.09 mm. Subfoveal choroid thickened by 1.3 µm/year (95% confidence interval [CI] = 0.6-2.0), but this was reduced by 0.9 µm/year (95% CI = 1.6-0.2) for every 1 mm increase in axial length. For every 10 µm increase in baseline ChT, average annual change in spherical equivalent and axial length reduced by 0.006 D/year and 0.003 mm/year, respectively.In a community-based cohort of young adults, the choroid continued to change during early adulthood. Choroidal thickening was less in eyes that were longer at baseline, and the choroid thinned in eyes that showed myopia progression. The association between baseline ChT and longitudinal changes in spherical equivalent and axial length supports the hypothesis that ChT may be predictive of refractive error development and/or myopia progression.

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).Cross-sectional study.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.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 ChTs300 μm (P = .019) and absent in eyes with ChTs300 μm.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.

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.

Executive function and visual search are linked to a number of activities of daily living including driving and mobility. Using a computerised version of the Trail Making Test B (TMT-B), we compared the executive function and visual search ability of older adults with glaucoma to age-similar controls and identified which visual function tests best predict TMT-B performance. Novel low-contrast and shifting-target variations of the test were incorporated to explore the effects of different levels of test complexity.Thirty-one older adults with mild to moderate glaucoma (mean age = 71.2 years [SD 6.9]; better-eye mean deviation [MD]: median = -1.9 dB [IQR = -1.2 to 0.4], worse-eye MD: median = -11.1 dB [IQR = -14.0 to -7.7]) and 24 age-similar controls (mean age = 71.9 years [SD 6.6]) with normal vision participated. The groups were matched in age, sex, and cognitive status (mini-mental state examination [MMSE]). Participants underwent measurements of visual acuity, contrast sensitivity (CS), visual fields, and visual processing speeds using the useful field-of-view (UFoV). Participants then completed four variations of a computerised TMT-B test, with different levels of complexity based on target contrast (high/low-contrast) and shifts in target position (fixed/shifting locations). Linear mixed-effect models were used to explore the effects of group, target contrast and shift on TMT-B completion time.The glaucoma group took 17.3s longer than controls to complete the TMT-B (P = 0.028). All participants took 6.5s longer to complete the low- compared to the high-contrast tests (P = 0.012), and 10.6s longer for the shifting TMT-B compared to the fixed version (P 0.001). There was no interaction effect between group, contrast, or target shift on completion time. Across all tests and participant groups, longer completion time was associated with slower UFoV processing speeds (divided attention: P = 0.003; selective attention: P = 0.006). Poorer CS was associated with longer completion times for the low (P = 0.007), but not the high-contrast tests.Our findings suggest that older adults with mild to moderate glaucoma have poorer visual search ability and executive function relative to controls. However, decreasing target contrast or shifting target position did not exacerbate the effects of glaucomatous visual impairment on performance. The UFoV was a strong predictor of TMT-B performance.

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.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.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 (AHI5 events/h), mild (AHI 5 to 15), moderate (AHI 16 to 30), or severe OSA (AHI30). 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.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 (P0.001 and 0.001, respectively). In addition, superotemporal RNFL was inversely associated with AHI (P=0.004) and sleep time with oxygen saturation level90% (P=0.005). There was no association between OSA measures and Bruch membrane opening-minimum rim widths.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.

Importance Myopia incidence and progression has been described extensively in children. However, few data exist regarding myopia incidence and progression in early adulthood.\ud\udObjective To describe the 8-year incidence of myopia and change in ocular biometry in young adults and their association with the known risk factors for childhood myopia.\ud\udDesign, Setting, and Participants The Raine Study is a prospective single-center cohort study. Baseline and follow-up eye assessments were conducted from January 2010 to August 2012 and from March 2018 to March 2020. The data were analyzed from June to July 2021. A total of 1328 participants attended the baseline assessment, and 813 participants attended the follow-up assessment. Refractive information from both visits was available for 701 participants. Participants with keratoconus, previous corneal surgery, or recent orthokeratology wear were excluded.\ud\udExposures Participants’ eyes were examined at ages 20 years (baseline) and 28 years.\ud\udMain Outcomes and Measures Incidence of myopia and high myopia; change in spherical equivalent (SE) and axial length (AL).\ud\udResults A total of 516 (261 male [50.6%]) and 698 (349 male [50.0%]) participants without myopia or high myopia at baseline, respectively, were included in the incidences analyses, while 691 participants (339 male [49%]) were included in the progression analysis. The 8-year myopia and high myopia incidence were 14.0% (95% CI, 11.5%-17.4%) and 0.7% (95% CI, 0.3%-1.2%), respectively. A myopic shift (of 0.50 diopters [D] or greater in at least 1 eye) occurred in 261 participants (37.8%). Statistical significance was found in longitudinal changes in SE (−0.04 D per year; P

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.Cross-sectional cohort study.Eight hundred forty-eight adults 19 to 22 years of age.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 (AHI5 events/hour), mild OSA (AHI ≥ 5 and15 events/hour), moderate OSA (AHI ≥ 15 and30 events/hour), or severe OSA (AHI ≥ 30 events/hour).Neuroretinal rim area, horizontal and vertical widths, and peripapillary retinal nerve fiber layer (RNFL) thickness.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.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.

SIGNIFICANCE Glaucoma has been shown to impair hazard detection ability and increase crash risk compared to controls. Differences in visual search behavior of the driving scene may explain these differences; however, there has been limited investigation of this issue with inconsistent findings. PURPOSE Through eye movement tracking of older drivers with glaucoma, we explored their visual search behavior in comparison with controls while performing the DriveSafe, a slide recognition test purported to predict fitness to drive. METHODS Thirty-one drivers with glaucoma (mean age, 71.7 ± 6.3 years; average better-eye mean defect,-3 dB; average worse-eye mean defect,-12 dB) and 25 age-matched controls underwent measurements of their visual acuity, contrast sensitivity, visual fields, and useful field of view (visual processing speeds). Participants' eye movements were recorded while they completed the DriveSafe test, which consists of brief presentations of static, real-world driving scenes containing various road users (pedestrians, bicycles, vehicles). Participants reported the types, positions, and direction of travel of road users in each image; the score was the total number of correctly reported items (maximum, 128). RESULTS Drivers with glaucoma had significantly worse DriveSafe scores (P = .03), fixated on road users for shorter durations (P < .001), and exhibited smaller saccades (P = .02) compared with controls. For all participants, longer fixation times on road users (P < .001) was the eye movement measure most strongly associated with better DriveSafe scores; this relationship was not significantly different between groups. Useful field-of-view divided attention was the strongest visual predictor of DriveSafe scores. CONCLUSIONS Eye movement changes in the glaucoma group may reflect increased difficulty in identifying relevant objects in the visual scene, which may be related to their lower DriveSafe scores. Given the DriveSafe's potential utility in assessing drivers with visual impairment before on-road testing, further investigations on how DriveSafe performance and eye movement patterns compare to those during on-road driving are warranted.

Inflammation and cigarette smoking predispose to macular diseases, and choroidal and retinal thinning. We explored the choroidal and retinal thicknesses in young adults against their 7-year C-reactive protein (CRP) level trajectory and pack-years smoked. Participants from the Raine study, a longitudinal cohort study, had serum CRP levels analysed at the 14-, 17-, and 20-year follow-ups. Group-based trajectory modelling was used to classify participants according to their 7-year CRP levels. At the 20-year follow-up (at 18–22 years old), participants completed questionnaires on their smoking history, and underwent optical coherence tomography imaging to obtain their choroidal and retinal thicknesses at the macula. Three CRP trajectories were identified: consistently low CRP levels (78% of sample), increasing (11%), or consistently high (11%). 340 and 1035 participants were included in the choroidal and retinal thickness analyses, respectively. Compared to those in the “Low” trajectory group, participants in the “Increasing” and “High” groups had 14–21 μm thinner choroids at most macular regions. Every additional pack-year smoked was linked with a 0.06–0.10 μm thinner retina at the inner and outer macular rings, suggesting a dose-dependent relationship between smoking and thinner retinas. These associations may suggest that an increased risk of future visual impairment or eye disease associated with these risk factors may be present since young adulthood.

Purpose: To describe the thickness profiles of the full retinal and outer retinal layers (ORL) at the macula in healthy young adults, and associations with best-corrected visual acuity (BCVA). Methods: In total, 1604 participants (19-30 years) underwent an eye examination that included measurements of their BCVA, axial length, and autorefraction. The retinal thickness at the foveal pit and at the nine Early Treatment of Diabetic Retinopathy Study macular regions (0.5-mm radius around the fovea, and superior, inferior, temporal, and nasal quadrants of the inner and outer rings of the macula) were obtained using spectral-domain optical coherence tomography imaging. A custom program was used to correct for transverse magnification effects because of different axial lengths. Results: The median full retinal and ORL thicknesses at the central macula were 285 µm and 92 µm. The full retina was thinnest centrally and thickest at the inner macula ring, whereas the ORL was thickest centrally and gradually decreased in thickness with increasing eccentricity. There was no association between axial length and the full retinal or ORL thickness. Increased thicknesses of the full retina at the central macula was associated with better BCVA; however, the effect size was small and not clinically significant. Conclusions: This article mapped the full retinal and ORL thickness profile in a population-based sample of young healthy adults. Translational relevance: Thickness values presented in this article could be used as a normative reference for future studies on young adults and in clinical practice.

It is well accepted that a myopia epidemic is occurring globally, with 50% of the global population predicted to have myopia by the year 2050. Parts of East and Southeast Asia, such as China, South Korea, and Singapore, have the most rapidly increasing rates of myopia compared to other parts of the world. The rate of rise in myopia differs between geographical locations and, even within a country, varying according to the level of urbanization of the studied region and between ethnic groups. Genetic factors are known to play a part in the myopia epidemic, with over 100 genes associated with myopia or its ocular traits already identified. Children in families where one or both parents have myopia are more likely to develop myopia. However, the epidemic is likely to be the result of environmental risk factors, such as higher levels of education, increased near work, and decreased time spent outdoors, rather than genetic factors. These environmental factors may predispose individuals who are genetically susceptible to develop myopia and may provide a target for early intervention and prevention.

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.

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

IntroductionEye 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 analysisParticipants 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 disseminationThe 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 numberACTRN12617001599369; Active, not recruiting.

Purpose: To report the distribution of peripapillary retinal nerve fiber layer (RNFL) thickness in healthy young adults, investigate factors associated with RNFL thickness, and report the percentage of outside normal limits (ONL) and borderline (BL) RNFL thickness classifications based on the optical coherence tomography (OCT) manufacturer reference database. Methods: Participants of the Raine Study Generation 2 cohort (aged 18–22 years) underwent spectral domain OCT imaging with an RNFL circle scan. Eyes with inadequate scans or optic nerve pathology were excluded. Linear mixed models were used to analyze associations. Results: Data were available for 1288 participants (mean age, 20.0 years). Mean RNFL thicknesses in right and left eyes, respectively, were global = 100.5 µm, 100.3 µm (P = 0.03); temporal = 73.1 µm, 68.9 µm (P < 0.001); superotemporal = 140.6 µm, 136.3 µm (P < 0.001); superonasal = 104.9 µm, 115.1 µm (P < 0.001); nasal = 79.7 µm, 79.1 µm (P = 0.09); inferonasal = 109.8 µm, 111.5 µm (P < 0.001); and inferotemporal = 143.2 µm, 143.6 µm (P = 0.51). Longer axial length was associated with thinner RNFL globally, nasally, inferotemporally, superotemporally, superonasally, and inferonasally, as well as thicker RNFL temporally. The prevalence of ONL and BL classifications was generally higher than the expected rates of 1% and 4%, respectively, in temporal sectors and lower than expected in nasal sectors. The prevalence of global BL classifications was lower than expected (right eye, 2.3%; left eye, 2.6%). Conclusions: Measured RNFL thickness differs with axial length and between right and left eyes. More reference data are needed to better define the normal limits of RNFL variation in different populations. Translational Relevance: This study provides an improved understanding of normal variation in RNFL thickness in young adults.

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.

Purpose To assess the link between visual scanning behaviour and closed-road driving performance in older drivers with glaucomatous visual impairment. Methods Participants included 13 older drivers with glaucoma (mean age=72.0±6.7 years; average better-eye mean deviation [MD])= −2.9±2.1dB, average worse-eye MD=−12.5±7.1dB) and ten visually-normal controls (mean age=70.6±7.4 years). Visual acuity, contrast sensitivity, visual fields, useful field-of-view (UFoV), and motion sensitivity were assessed. Participants drove around a closed-road circuit while their eye movements were recorded with an ASL Mobile Eye-XG, and head movements recorded using the gyroscope sensors of a smart phone. Measures of driving performance included hazards hit, sign recognition, and lane-crossing time; an overall driving score was derived from these component measures. Results Participants with glaucoma had significantly poorer overall driving scores (p=0.026) and hit more hazards (p=0.043) than controls. The glaucoma group also exhibited larger saccades (p

Purpose Optical blur and ageing are known to affect driving performance but their effects on drivers' eye movements are poorly understood. This study examined the effects of optical blur and age on eye movement patterns and performance on the DriveSafe slide recognition test which is purported to predict fitness to drive. Methods Twenty young (27.1 ± 4.6 years) and 20 older (73.3 ± 5.7 years) visually normal drivers performed the DriveSafe under two visual conditions: best-corrected vision and with +2.00 DS blur. The DriveSafe is a Visual Recognition Slide Test that consists of brief presentations of static, real-world driving scenes containing different road users (pedestrians, bicycles and vehicles). Participants reported the types, relative positions and direction of travel of the road users in each image; the score was the number of correctly reported items (maximum score of 128). Eye movements were recorded while participants performed the DriveSafe test using a Tobii TX300 eye tracking system. Results There was a significant main effect of blur on DriveSafe scores (best-corrected: 114.9 vs blur: 93.2; p < 0.001). There was also a significant age and blur interaction on the DriveSafe scores (p < 0.001) such that the young drivers were more negatively affected by blur than the older drivers (reductions of 22% and 13% respectively; p < 0.001): with best-corrected vision, the young drivers performed better than the older drivers (DriveSafe scores: 118.4 vs 111.5; p = 0.001), while with blur, the young drivers performed worse than the older drivers (88.6 vs 95.9; p = 0.009). For the eye movement patterns, blur significantly reduced the number of fixations on road users (best-corrected: 5.1 vs blur: 4.5; p < 0.001), fixation duration on road users (2.0 s vs 1.8 s; p < 0.001) and saccade amplitudes (7.4° vs 6.7°; p < 0.001). A main effect of age on eye movements was also found where older drivers made smaller saccades than the young drivers (6.7° vs 7.4°; p < 0.001). Conclusions Blur reduced DriveSafe scores for both age groups and this effect was greater for the young drivers. The decrease in number of fixations and fixation duration on road users, as well as the reduction in saccade amplitudes under the blurred condition, highlight the difficulty experienced in performing the task in the presence of optical blur, which suggests that uncorrected refractive errors may have a detrimental impact on aspects of driving performance.

Purpose - To examine the effects of optical blur, auditory distractors and age on eye movement patterns while performing a driving hazard perception test (HPT). Methods - Twenty young (mean age 27.1 ± 4.6 years) and 20 older (73.3 ± 5.7 years) drivers with normal vision completed a HPT in a repeated-measures counterbalanced design while their eye movements were recorded. Testing was performed under two visual (best-corrected vision and with +2.00DS blur) and two distractor (with and without auditory distraction) conditions. Participants were required to respond to road hazards appearing in the HPT videos of real-world driving scenes and their hazard response times were recorded. Results - Blur and distractors each significantly delayed hazard response time, by 0.42 and 0.76s respectively (p

Dry eye is prevalent in many parts of the world. As a result, ophthalmologists and other health care professionals, such as optometrists and general practitioners, often help these patients manage their symptoms. The most common form of treatment for management of dry eye is over-the-counter tear lubricants. A number of tear lubricant formulations are available that vary by their mechanism of action. This article suggests simple guidelines on how lubricants can be selected for patients with mild to moderate dry eye. Side effects of lubricants, such as burning on instillation because of mismatches of eye drop with tear acidity, are also discussed.

Purpose: Systemic diseases, smoking, ocular surgeries and contact lens wear have been linked with dry eye but it is not known if these factors are also associated with severity of dry eye. A cross-sectional investigation was conducted on the effect of various systemic and ocular conditions with respect to the severity of dry eye in Asian patients. Methods: Prospective recruitment of consecutive new referral patients from a dry eye clinic was performed. Medical history, dry eye symptoms and clinical assessment were coded in a standardised form and analysed. Results: Out of 510 patients (25% men), mean ± S.D. age 53.0 ± 14.1 years, 25 had previous diagnosis of rheumatoid arthritis, 30 had diabetic mellitus, 41 had thyroid disease, and 33 were current smokers; 23 and 41 patients had previous LASIK and cataract surgery respectively and 90 were current contact lenses wearers. A previous diagnosis of rheumatoid arthritis was associated with more severe superior corneal fluorescein staining (OR = 11.2, 95% CI 4.6‐ 27.4). Conclusion: Generally, with the exception of rheumatoid arthritis, there were no associations between dry eye severity and systemic diseases, smoking, previous ocular surgeries and contact lens wear. Dry eye patients with rheumatoid arthritis tend to have more severe ocular surface damage in the superior cornea.

Purpose The mechanisms underlying the elevated crash rates of older drivers with glaucoma are poorly understood. A key driving skill is timely detection of hazards; however, the hazard detection ability of drivers with glaucoma has been largely unexplored. This study assessed the eye movement patterns and visual predictors of performance on a laboratory-based hazard detection task in older drivers with glaucoma. Methods Participants included 30 older drivers with glaucoma (71±7 years; average better-eye mean deviation (MD) = −3.1±3.2 dB; average worse-eye MD = −11.9±6.2 dB) and 25 age-matched controls (72±7 years). Visual acuity, contrast sensitivity, visual fields, useful field of view (UFoV; processing speeds), and motion sensitivity were assessed. Participants completed a computerised Hazard Perception Test (HPT) while their eye movements were recorded using a desk-mounted Tobii TX300 eye-tracking system. The HPT comprises a series of real-world traffic videos recorded from the driver’s perspective; participants responded to road hazards appearing in the videos, and hazard response times were determined. Results Participants with glaucoma exhibited an average of 0.42 seconds delay in hazard response time (p = 0.001), smaller saccades (p = 0.010), and delayed first fixation on hazards (p

To evaluate the tear film osmolarity (TFO) and ocular surface clinical signs and symptoms in chronically medicated glaucoma patients and post-trabeculectomy patients.This is a single-center, prospective case-controlled study. One-hundred and thirty eyes of 130 participants aged ≥ 45 years were included (49 normal controls, 50 glaucoma patients on chronic preserved anti-glaucoma medication ≥ 6 months, and 31 post-trabeculectomy patients not on medication ≥ 6 months). TFO, tear break-up time (TBUT), Schirmer's test I and dry eye symptoms were evaluated. Data from both groups of glaucoma patients were compared with age and sex-matched controls. Logistic regression was performed to calculate the odds ratios.Mean TFO in the three groups were 301.4 ± 7.7, 307.0 ± 9.3, and 307.4 ± 11.6 mOsm/l, respectively. Compared with normal controls, chronically medicated glaucoma patients and post-trabeculectomy patients were more likely to have a raised TFO, with odds ratios (95% CI) of 4.43 (1.74-11.32) and 2.76 (1.02-7.94), respectively. Both groups of glaucoma patients were also more likely to experience dry eye symptoms, with ORs of 4.72 (1.92-11.59) and 4.24 (1.54-11.72). There was no significant difference in TFO and symptoms between both groups of glaucoma patients, and in TBUT and Schirmer's test across all three groups.Patients on chronic topical anti-glaucoma medication and post-trabeculectomy patients were more likely to have raised TFO and dry eye symptoms, suggesting significant ocular surface disease. Glaucoma practitioners should be aware that dry eye symptoms and raised TFO may occur in the absence of TBUT and Schirmer's test abnormality.

The purpose of this study was to evaluate the repeatability of tear evaporimetry based on infrared thermography in a clinical room setting and to test the effect of changing environmental humidity on ocular surface temperature (OST) and tear evaporation rates (TERs) in a controlled adverse environmental (CAE) chamber.Twenty-six healthy participants were enrolled, of whom 16 underwent repeatability measurements in a clinical room and 10 were exposed to a constant temperature of 30°C with a humidity of 45 and 65% in a CAE. Participants were acclimatized to each condition for at least 20 minutes before OSTs were taken. Tear film breakup time was assessed in the CAE only. Number of blinks and OSTs were continuously measured for 20 seconds for the cornea, conjunctiva, and overall ocular surface with an infrared camera; corresponding TERs were calculated.The OSTs and TERs showed acceptable strength of agreement between the first and second measurements. The coefficients of repeatability were 0.4°C for OST and 6.0 W m for TER. An increase in chamber humidity (from 45 to 65%) increased OST (p0.05). The TER was not changed significantly (p0.05). The tear film breakup time and number of blinks were not significantly affected by different humidity conditions.This technique has acceptable repeatability and has potential to document individual tear evaporation changes with time where humidity may differ by less than 20%.

Prolonged visually stressful activities aggravate dry eye disease (DED). The duration spent on such activities and their relationship with DED clinical features were investigated. Patients completed an activity log as they performed their usual activities over 1 typical rest day and 1 typical work day. The log included time spent in an air-conditioned environment, windy environment, driving, watching television, computer use, reading, watching a movie in the theatre, and wearing contact lens. Average daily activity hours were calculated and correlated with clinical features of DED. Thirty-five logs were returned. Positive correlation was found between watching television and episodic blurred vision (P<0.01). Computer use was negatively correlated with episodic blur vision, burning sensation, and gritty sensation (P<0.05). Negative correlation was found between time spent in windy environments, driving, reading, and certain DED symptoms (P<0.05). Reading correlated positively with severity of corneal fluorescein staining and reduced Schirmer’s values (P<0.03). The use of air conditioning correlated negatively with episodic blur vision but positively with visual blurring that improves with lubricants (P=0.02). This study is the first to evaluate the relationship between time spent on DED-aggravating activities and DED clinical features. Negative correlations between certain activities and DED symptoms suggest an unconscious modification of lifestyle to alleviate symptoms.

apparent discrepancy with a previous study. 2 First, the authors 1 classified subjects as controls based on Schirmer test results of 10 mm and tear break-up times (TBUT) of 10 seconds. It is not clear from the paper if the meibomian gland dysfunction (MGD) score of 18 had to be fulfilled in this group. Without knowledge of the mean and SD of the MGD score, this group is insufficiently characterized. Second, the positions of “*” and “†” in Table 1 appear to have been swapped. The text in the Materials and Methods section states the MGD score criterion is mandatory for the DRYlip group rather than the DRYaq group, and vice versa in Table 1. Third, the very strong and significant correlations between tear cytokines (IL-6, IL-8, TNFalpha, and IFN gamma) with TBUT in the control subjects (r values 0.80, 0.74, 0.67, and 0.78, respectively), as reported in Supplementary Table 1B, 1 are puzzling. These correlations are of a higher magnitude than that of other correlations reported elsewhere in this study