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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.

Background: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines., Methods: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention., Discussion: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated., Trial Registration: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022., (© 2023. The Author(s).)

Purpose: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii; however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study., Design: Cross-sectional, community-based, prospective cohort study., Participants: 5020 Australian adults (2264 men and 2756 women; age range, 45-69 years, and median age, 58 years)., Methods: Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis., Main Outcome Measures: Prevalence of toxoplasmic retinochoroiditis., Results: Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021;11:3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67% or 1 per 149 persons., Conclusions: Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: To investigate the relationship between dietary intake of niacin (water-soluble form of vitamin B 3 ) and retinal nerve fibre layer (RNFL) thickness in healthy eyes., Methods: This cross-sectional study examined the association between daily niacin intake and RNFL thickness in three large population-based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data; energy-adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed-effects models were utilised to examine the association between RNFL thickness and energy-adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable., Results: In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20; Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64; TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI β: Raine Study Gen 2, -0.174 to 0.074; BHAS, -0.066 to 0.078; TwinsUK -0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts., Conclusions: Dietary intake of niacin from a standard diet does not appear to be associated with age-related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina., (© 2022 Royal Australian and New Zealand College of Ophthalmologists.)

Background: Heterozygous c.440 G > T mutation in the S-antigen visual arrestin (SAG) gene has been described as a cause of autosomal dominant retinitis pigmentosa (adRP) in a series of patients of Hispanic origin. This study presents the early and late clinical features and disease progression rates in an Australian family with SAG adRP., Materials and Methods: An observational case series of four family members with adRP. They were examined clinically, with multi-modal retinal imaging and electroretinography (ERG) to ascertain phenotype. Disease progression rate was measured using optical coherence tomography (OCT) and fundus autofluorescence (FAF). A retinal dystrophy panel was used for the proband and cascade testing with targeted Sanger sequencing was conducted in other available family members., Results: The proband presented at 36 years of age with profoundly reduced full-field ERG responses despite a sector RP phenotype. This progressed to a classic RP pattern over several decades leaving a small residual island of central visual field. The horizontal span of the residual outer nuclear layer and the area of hyperautofluorescent ring contracted at a rate of 8-11% and 9-14% per year, respectively. DNA sequencing confirmed the segregation of SAG c.440 G > T mutation with disease., Conclusion: SAG adRP presents with a reduced full-field ERG response consistent with a rod-cone dystrophy in mid-life despite a sector RP phenotype. Centripetal progression of the disease into the macula can be tracked by OCT and FAF imaging.

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., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

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.)

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.