Polygenic Prediction of Keratoconus and its Measures: Cross-Sectional and Longitudinal Analyses in Community-Based Young Adults.

AIM: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus. DESIGN: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.6, were each analyzed against the PRS using linear and logistic regression, respectively. RESULTS: Prevalence of keratoconus was 2.5% (95% confidence interval [CI] = 1.9-3.6) in the cross-sectional cohort. Each z-score increase in PRS was associated with worse BAD-D z-score by 0.13 (95%CI = 0.08-0.18) and 1.6 increased odds of keratoconus. The 8-year keratoconus incidence was 2.6% (95%CI = 1.3-4.0). Participants in the highest PRS decile were more likely to have incident keratoconus compared to the rest of the cohort (odds ratio = 3.85, 95%CI = 1.21-12.22). For each z-score increase in PRS, 8-year change in BAD-D z-score worsened by 0.11 (95%CI = 0.04-0.17). CONCLUSIONS: A PRS for keratoconus could be useful in predicting incident keratoconus and progression, demonstrating its potential utility in clinical settings to identify patients at high risk of postsurgery ectasia or those who may benefit most from keratoconus intervention.

Myopia progression following 0.01% atropine cessation in Australian children: Findings from the Western Australia - Atropine for the Treatment of Myopia (WA-ATOM) study.

BACKGROUND: A rebound in myopia progression following cessation of atropine eyedrops has been reported, yet there is limited data on the effects of stopping 0.01% atropine compared to placebo control. This study tested the hypothesis that there is minimal rebound myopia progression after cessation of 0.01% atropine eyedrops, compared to a placebo. METHODS: Children with myopia (n = 153) were randomised to receive 0.01% atropine eyedrops or a placebo (2:1 ratio) daily at bedtime during the 2-year treatment phase of the study. In the third year (wash-out phase), all participants ceased eyedrop instillation. Participants underwent an eye examination every 6 months, including measurements of spherical equivalent (SphE) after cycloplegia and axial length (AL). Changes in the SphE and AL during the wash-out phase and throughout the 3 years of the study (treatment + wash-out phase) were compared between the treatment and control groups. RESULTS: During the 1-year wash-out phase, SphE and AL progressed by -0.41D (95% CI = -0.33 to -0.22) and +0.20 mm (95% CI = -0.46 to -0.36) in the treatment group compared to -0.28D (95% CI = 0.11 to 0.16) and +0.13 mm (95% CI = 0.18 to 0.21) in the control group. Progression in the treatment group was significantly faster than in the control group (p = 0.016 for SphE and <0.001 for AL). Over the 3-year study period, the cumulative myopia progression was similar between the atropine and the control groups. CONCLUSIONS: These findings showed evidence of rapid myopia progression following cessation of 0.01% atropine. Further investigations are warranted to ascertain the long-term effects of atropine eyedrops.

Changes in Refractive Error During Young Adulthood: The Effects of Longitudinal Screen Time, Ocular Sun Exposure, and Genetic Predisposition.

Purpose: Changes in refractive error during young adulthood is common yet risk factors at this age are largely unexplored. This study explored risk factors for these changes, including gene-environmental interactions. Methods: Spherical equivalent refraction (SER) and axial length (AL) for 624 community-based adults were measured at 20 (baseline) and 28 years old. Participants were genotyped and their polygenic scores (PGS) for refractive error calculated. Self-reported screen time (computer, television, and mobile devices) from 20 to 28 years old were collected prospectively and longitudinal trajectories were generated. Past sun exposure was quantified using conjunctival ultraviolet autofluorescence (CUVAF) area. Results: Median change in SER and AL were -0.023 diopters (D)/year (interquartile range [IQR] = -0.062 to -0.008) and +0.01 mm/year (IQR = 0.000 to 0.026), respectively. Sex, baseline myopia, parental myopia, screen time, CUVAF, and PGS were significantly associated with myopic shift. Collectively, these factors accounted for approximately 20% of the variance in refractive error change, with screen time, CUVAF, and PGS each explaining approximately 1% of the variance. Four trajectories for total screen time were found: "consistently low" (n = 148), "consistently high" (n = 250), "consistently very high" (n = 76), and "increasing" (n = 150). Myopic shift was faster in those with "consistently high" or "consistently very high" screen time compared to "consistently-low" (P ≤ 0.031). For each z-score increase in PGS, changes in SER and AL increased by -0.005 D/year and 0.002 mm/year (P ≤ 0.045). Of the three types of screen time, only computer time was associated with myopic shift (P ≤ 0.040). There was no two- or three-way interaction effect between PGS, CUVAF, or screen time (P ≥ 0.26). Conclusions: Higher total or computer screen time, less sun exposure, and genetic predisposition are each independently associated with greater myopic shifts during young adulthood. Given that these factors explained only a small amount of the variance, there are likely other factors driving refractive error change during young adulthood.

Distribution of Axial Length in Australians of Different Age Groups, Ethnicities, and Refractive Errors.

Purpose: Treatments are available to slow myopic axial elongation. Understanding normal axial length (AL) distributions will assist clinicians in choosing appropriate treatment for myopia. We report the distribution of AL in Australians of different age groups and refractive errors. Methods: Retrospectively collected spherical equivalent refraction (SER) and AL data of 5938 individuals aged 5 to 89 years from 8 Australian studies were included. Based on the SER, participants were classified as emmetropes, myopes, and hyperopes. Two regression model parameterizations (piece-wise and restricted cubic splines [RCS]) were applied to the cross-sectional data to analyze the association between age and AL. These results were compared with longitudinal data from the Raine Study where the AL was measured at age 20 (baseline) and 28 years. Results: A piece-wise regression model (with 1 knot) showed that myopes had a greater increase in AL before 18 years by 0.119 mm/year (P < 0.001) and after 18 years by 0.011 mm/year (P < 0.001) compared to emmetropes and hyperopes, with the RCS model (with 3 knots) showing similar results. The longitudinal data from the Raine Study revealed that, when compared to emmetropes, only myopes showed a significant change in the AL in young adulthood (by 0.016 mm/year, P < 0.001). Conclusions: The AL of myopic eyes increases more rapidly in childhood and slightly in early adulthood. Further studies of longitudinal changes in AL, particularly in childhood, are required to guide myopia interventions. Translational Relevance: The axial length of myopic eyes increases rapidly in childhood, and there is a minimal increase in the axial length in non-myopic eyes after 18 years of age.

IMI-Onset and Progression of Myopia in Young Adults.

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.

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration.

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).

Low-concentration atropine eyedrops for myopia control in a multi-racial cohort of Australian children: A randomised clinical trial.

BACKGROUND: To test the hypothesis that 0.01% atropine eyedrops are a safe and effective myopia-control approach in Australian children. METHODS: Children (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. RESULTS: At 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. CONCLUSIONS: In 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.

Prevalence and Risk Factors of Myopia in Young Adults: Review of Findings From the Raine Study.

Myopia tends to develop and progress fastest during childhood, and the age of stabilization has been reported to be 15-16 years old. Thus, most studies on myopia have centered on children. Data on the refractive error profile in young adulthood - a time in life when myopia is thought to have stabilized and refractive error is unaffected by age-related pathology such as cataract - are limited. The Raine Study has been following a community-based cohort of young adults representative of the general Western Australia population since their prenatal periods in 1989-1991, with eye examinations performed when participants were 20 and 28 years old. At 20 years old, prevalence of myopia in the cohort was 25.8%. Using long-term trajectory of serum vitamin D levels and conjunctival ultraviolet autofluorescence (CUVAF) area to objectively quantify sun exposure, the Raine Study confirmed a negative relationship between time spent outdoors and myopia prevalence. However, prospective studies are required to determine the amount of CUVAF area or serum vitamin D levels associated with time duration. Combining data from the Raine Study and several other cohorts, Mendelian randomization studies have confirmed a link between myopia and a genetic predisposition toward higher education. Several novel potential associations of myopia or ocular biometry were investigated, including fetal growth trajectory, which was found to be significantly associated with corneal curvature at 20 years. By age 28, myopia prevalence had increased to 33.2%. Between 20 and 28 years old, myopia progressed and axial length elongated, on average, by -0.041D/year and 0.02 mm/year, respectively. Smaller CUVAF area at follow-up, female sex, and parental myopia were significant risk factors for myopia incidence and progression between 20 and 28 years. Given the limited research in young adults, further investigations are warranted to confirm the Raine Study findings, as well as identify novel genetic or environmental factors of myopia incidence and progression in this age group.

Choroidal Thickening During Young Adulthood and Baseline Choroidal Thickness Predicts Refractive Error Change.

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Glaucoma - risk factors and current challenges in the diagnosis of a leading cause of visual impairment.

Worldwide, glaucoma affects about 3% of the population over the age of 50 years and is a leading cause of irreversible visual impairment among older people. Because glaucoma is asymptomatic in its early stages and can be challenging to diagnose clinically, it often remains undiagnosed until substantial vision loss has occurred. Efficient methods of glaucoma screening are therefore warranted for early detection of disease. Identification of risk factors for glaucoma - family history of glaucoma, older age, African or Asian ethnicities, raised intraocular pressure, and thin corneas - have helped inform guidelines on the recommended age at commencement and frequency of glaucoma screenings. A genetic predisposition or family history of glaucoma is one of the most important risk factors for the disease. However, an accurate family history cannot always be ascertained. Genetic testing for genes such as myocilin could help to identify high-risk individuals and, with further research, could even provide insight into individual patients' response to treatment. With the ongoing discovery of glaucoma-associated genes and the advent of polygenic risk scores to identify individuals at high risk of glaucoma, gene-based screening for glaucoma is becoming closer to realisation. In the meantime, regularly screening family members of people with existing glaucoma is an efficient way of detecting early glaucoma. Raising public awareness of glaucoma is also necessary to educate the general public on the key role of routine eye examinations and early disease detection. Future studies should be undertaken to explore efficient public health campaign methods for improving glaucoma awareness.

The effect of transverse ocular magnification adjustment on macular thickness profile in different refractive errors in community-based adults.

PURPOSE: Changes in retinal thickness are common in various ocular diseases. Transverse magnification due to differing ocular biometrics, in particular axial length, affects measurement of retinal thickness in different regions. This study evaluated the effect of axial length and refractive error on measured macular thickness in two community-based cohorts of healthy young adults. METHODS: A total of 2160 eyes of 1247 community-based participants (18-30 years; 23.4% myopes, mean axial length = 23.6mm) were included in this analysis. Macular thickness measurements were obtained using a spectral-domain optical coherence tomography (which assumes an axial length of 24.385mm). Using a custom program, retinal thickness data were extracted at the 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions with and without correction for transverse magnificent effects, with the corrected measurements adjusting according to the participant's axial length. Linear mixed models were used to analyse the effect of correction and its interaction with axial length or refractive group on retinal thickness. RESULTS: The raw measures (uncorrected for axial length) underestimated the true retinal thickness at the central macula, while overestimating at most non-central macular regions. There was an axial length by correction interaction effect in all but the nasal regions (all p<0.05). For each 1mm increase in axial length, the central macular thickness is overestimated by 2.7-2.9µm while thicknesses at other regions were underestimated by 0.2-4.1µm. Based on the raw thickness measurements, myopes have thinner retinas than non-myopes at most non-central macular. However, this difference was no longer significant when the corrected data was used. CONCLUSION: In a community-based sample, the raw measurements underestimate the retinal thickness at the central macula and overestimate the retinal thickness at non-central regions of the ETDRS grid. The effect of axial length and refractive error on retinal thickness is reduced after correcting for transverse magnification effects resulting from axial length differences.

Incidence and Progression of Myopia in Early Adulthood.

IMPORTANCE: Myopia incidence and progression has been described extensively in children. However, few data exist regarding myopia incidence and progression in early adulthood. OBJECTIVE: 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. DESIGN, 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. EXPOSURES: Participants' eyes were examined at ages 20 years (baseline) and 28 years. MAIN OUTCOMES AND MEASURES: Incidence of myopia and high myopia; change in spherical equivalent (SE) and axial length (AL). RESULTS: 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 < .001), AL (0.02 mm per year; P <.001), and lens thickness (0.02 mm per year; P < .001). Incident myopia was associated with self-reported East Asian vs White race (odds ratio [OR], 6.13; 95% CI, 1.06-35.25; P = .04), female vs male sex (OR, 1.81; 95% CI, 1.02-3.22; P = .04), smaller conjunctival ultraviolet autofluorescence area (per 10-mm2 decrease, indicating less sun exposure; OR, 9.86; 95% CI, 9.76-9.97; P = <.009), and parental myopia (per parent; OR, 1.57; 95% CI, 1.03-2.38; P = <.05). Rates of myopia progression and axial elongation were faster in female participants (estimate: SE, 0.02 D per year; 95 % CI, 0.01-0.02 and AL, 0.007 mm per year, 95 % CI, 0.00.-0.011; P ≤ .001) and those with parental myopia (estimate per parent: SE, 0.01 D per year; 95% CI, 0.00-0.02 and AL, 95% CI, 0.002-0.008; P ≤ .001). Education level was not associated with myopia incidence or progression. CONCLUSIONS AND RELEVANCE: These findings suggest myopia progression continues for more than one-third of adults during the third decade of life, albeit at lower rates than during childhood. The protective effects of time outdoors against myopia may continue into young adulthood.

Associations of 12-year sleep behaviour trajectories from childhood to adolescence with myopia and ocular biometry during young adulthood.

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 Smoking and Alcohol, and Passive Smoking during Childhood: Effect on the Retinal Nerve Fibre Layer in Young Adulthood.

PURPOSE: 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 smoking during childhood had not been considered. We explored RNFL thickness in young adults in relation to these early life factors. METHODS: In 1989-1991, pregnant women completed questionnaires on their current smoking and alcohol drinking patterns. Following the birth of their offspring, information on household smokers was obtained between the 1- and 13-year follow-ups. At the 20-year follow-up, these offspring underwent an eye examination including optical coherence tomography imaging of the RNFL. RESULTS: Participants (n = 1,287) were 19-22 years old at time of eye examination. Most participants (77%) had no in utero exposure to cigarette smoke; 1.3% were initially exposed but not after 18 weeks' gestation, while 21% had continual in utero smoking exposure. Half of the mothers never consumed alcohol or only consumed alcohol once during their pregnancies. After correcting for potential confounders, including in utero alcohel exposure and childhood passive smoking, participants who had continued in utero exposure to >10 cigarettes/day and ≤10 cigarettes/day had thinner RNFLs by 6.6 (95% confidence interval [CI] = 4.4-8.7) and 3.7 µm (95%[CI] = 2.3-5.5), respectively, than those with no exposure (p < .001). In utero alcohol exposure and childhood passive smoking were not significantly associated with RNFL thickness after accounting for in utero exposure to smoking. CONCLUSIONS: In utero exposure to cigarette smoke is associated with thinner RFNL in young adulthood, independent of other early life environmental factors.

Distribution and Classification of Peripapillary Retinal Nerve Fiber Layer Thickness in Healthy Young Adults.

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.

Change in the prevalence of myopia in Australian middle-aged adults across 20 years.

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 < 0.001). The contemporary coastal-regional BHAS had a higher age-standardised myopia prevalence than the regional MVIP cohort (19.4% vs. 13.8%, p = 0.001). CONCLUSIONS: We report an increase in myopia prevalence in older adults in Australia born after World War ll compared to cohorts born before, accounting for urban/regional location. The prevalence of myopia remains relatively low in middle-aged Australian adults.

Physical Activity and Cardiovascular Fitness During Childhood and Adolescence: Association With Retinal Nerve Fibre Layer Thickness in Young Adulthood.

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<0.001], superotemporally (by 0.4 µm; 95% CI=0.1-0.7; P=0.013), inferonasally (by 0.7 µm; 95% CI=0.1-0.9; P=0.002), and nasally (by 0.4 µm; 95% CI=0.1-0.7; P=0.006) per 10 Watt increase in PWC. CONCLUSIONS: The association between estimated cardiovascular fitness and pRNFL thickness suggests there may be overlapping mechanisms for cardiovascular health and retinal ganglion cell integrity. While the effect sizes were small, it is possible that larger effects and clinically significant associations may arise as we follow this cohort of participants through their later adulthood.

Macular Thickness Profile and Its Association With Best-Corrected Visual Acuity in Healthy Young Adults.

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.