Charlotte M. McKnight

Myopia is associated with lower Vitamin D status in young adults.

PURPOSE To investigate the association between serum vitamin D levels and myopia in young adults. METHODS A total of 946 individuals participating in the 20-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study were included in this study. Ethnicity, parental myopia, and education status were ascertained by self-reported questionnaire. A comprehensive ophthalmic examination was performed, including postcycloplegic autorefraction and conjunctival UV autofluorescence photography. Serum 25-hydroxyvitamin D₃ (25(OH)D₃) concentrations were determined using mass spectrometry. The association between serum 25(OH)D₃ concentrations and prevalent myopia was determined using multivariable logistic regression. Myopia was defined as mean spherical equivalent ≤ -0.5 diopters. RESULTS Of the 946 participants, 221 (23.4%) had myopia (n = 725 nonmyopic). Myopic subjects had lower serum 25(OH)D₃ concentrations compared to nonmyopic participants (median 67.6 vs. 72.5 nmol, P = 0.003). In univariable analysis, lower serum 25(OH)D₃ concentration was associated with higher risk of having myopia (odds ratio [OR] for <50 vs. ≥50 nmol/L: 2.63; confidence interval [95% CI] 1.71-4.05; P < 0.001). This association persisted after adjustment for potential confounders, including age, sex, ethnicity, parental myopia, education status, and ocular sun-exposure biomarker score (adjusted OR 2.07; 95% CI 1.29-3.32; P = 0.002). CONCLUSIONS Myopic participants had significantly lower 25(OH)D₃ concentrations. The prevalence of myopia was significantly higher in individuals with vitamin D deficiency compared to the individuals with sufficient levels. Longitudinal studies are warranted to investigate whether higher serum 25(OH)D₃ concentration is protective against myopia or whether it is acting as a proxy for some other biologically effective consequence of sun exposure.

Myopia in Young Adults Is Inversely Related to an Objective Marker of Ocular Sun Exposure: The Western Australian Raine Cohort Study

PURPOSE To determine the association between ocular sun exposure measured by conjunctival ultraviolet (UV) autofluorescence and myopic refractive error in young adults. DESIGN Cross-sectional study. METHODS setting: Population-based cohort in Western Australia. study population: Total of 1344 mostly white subjects aged 19-22 years in the Western Australian Pregnancy Cohort (Raine) Eye Health Study. observation procedures: Cycloplegic autorefraction, conjunctival ultraviolet autofluorescence photography, participant questionnaire. main outcome measures: Prevalence of myopic refractive error (spherical equivalent less than -0.50 diopters) and area of conjunctival ultraviolet autofluorescence in mm(2). RESULTS There was an inverse relationship between myopic refractive error and ocular sun exposure, with more than double the prevalence of myopia in the lowest quartile of conjunctival autofluorescence than the highest quartile (33.0% vs 15.6%). Median area of autofluorescence was significantly lower in myopic than in nonmyopic subjects (31.9 mm(2) vs 47.9 mm(2), P < .001). These differences remained significant after adjustment for age, sex, parental history of myopia, and subject level of education. The use of corrective lenses did not explain the lower conjunctival autofluorescence observed in myopic subjects. CONCLUSIONS In this young adult population, myopic refractive error was inversely associated with objectively measured ocular sun exposure, even after adjustment for potential confounders. This further supports the inverse association between outdoor activity and myopia.

Myocardial infarction after intravitreal vascular endothelial growth factor inhibitors: a whole population study

Purpose: To determine the risk of thromboembolic and gastrointestinal bleeding events in the 12 months after injections of bevacizumab or ranibizumab compared with photodynamic therapy and a nontreated community sample. Methods: Hospital and death records were examined for 1,267 patients treated with vascular endothelial growth factor inhibitor and 399 patients treated with photodynamic therapy attending Western Australian eye clinics from 2002 to 2008, and 1,763 community controls, aged ≥50 years. Hospital records from 1995 to 2009 were analyzed for history of myocardial infarction (MI), stroke, and gastrointestinal bleeding before treatment. Records were searched for evidence of these events in the 12 months after treatment. Results: The 12-month MI rate was higher for vascular endothelial growth factor inhibitor patients than photodynamic therapy patientsand the community group (1.9/100 vs. 0.8 and 0.7, respectively). No differences were observed between patients treated with bevacizumab and ranibizumab. The adjusted MI rate was 2.3 times greater than the community group (95% confidence interval, 1.2–4.5) and photodynamic therapy rate (95% confidence interval, 0.7–7.7). The 12-month MI risk did not increase with the number of injections administered (hazard ratio, 0.9; 95% confidence interval, 0.5–1.5). Stroke and gastrointestinal bleeding did not differ between any exposure groups. Conclusion: Although all the adverse events examined were rare, patients treated with vascular endothelial growth factor inhibitors were significantly more likely to experience fatal or nonfatal MI than the community group. This increased risk may be related to the underlying age-related macular degeneration or vascular endothelial growth factor inhibitor use itself.

Elevated pressure induced astrocyte damage in the optic nerve

Astrocytes maintain an intimate relationship with central nervous system (CNS) neurons and play a crucial role in regulating their biochemical environment. A rise in neural tissue pressure in the CNS is known to lead to axonal degeneration however the response of astrocytes during the early stages of neural injury has not been studied in great detail. The optic nerve is a readily accessible model in which to study CNS axonal injury. Previous work from our laboratory has shown that an acute increase in intraocular pressure (IOP) results in axonal cytoskeleton changes and axonal transport retardation within the optic nerve head. Axonal changes occurred in a time-dependent manner with the magnitude of change being proportional to the duration of the IOP rise. Using glial fibrillary acidic protein (GFAP) as a marker of astrocytes we have now studied pressure induced changes in astrocyte structure in the optic nerve head. Using confocal microscopy we found that an increase in IOP resulted in morphological changes in the astrocytes that were consistent with previous reports of swelling. In addition there was also a decrease in GFAP intensity within these astrocytes. These changes occurred in a time-dependent manner with the chronology of change coinciding with that of axonal change. There was no evidence of apoptosis in regions where astrocyte changes were found. The present results provide evidence that in the early stages of neural tissue pressure rise there are both astrocyte and axonal injury.

Birth of a cohort - the first 20 years of the Raine study

n Th se I the beginning there was an idea ... and funding. e project might never have started if not for a rendipitous meeting between an accountant for the Raine Medical Research Foundation and a young obstetrician. The Foundation had been established 30 years earlier by the bequest of Mary Raine (Box 1), a successful businesswoman who left her property empire to the University of Western Australia (UWA) for medical research. The accountant mentioned that the Foundation had decided to award a large sum of money to one big, visionary project, and the very next day the grant application was underway. The obstetrician’s big idea, the Western Australian Pregnancy Cohort, had two objectives: to investigate the hypothesis that complications of pregnancy might be prevented by frequent ultrasound scans, and to develop a long-term cohort to study the role that early life events have on later health. From 1989 to 1991, 2900 pregnant women were randomly assigned to either routine obstetric ultrasound or multiple scans.1 Extensive data were collected during pregnancy and the children were assessed at birth and at ages 1, 2, 3, 5, 8, 10, 14, 17, 18 and 20 years (Box 2). Questionnaire data, physical measurements and biological samples were collected looking at growth, cardiovascular, respiratory, immunological, musculoskeletal, nutritional, psychiatric, neurocognitive and ophthalmic health. The current dataset contains more than 85 000 measures on each participant, as well as 2.5 million genetic variants, with an exponential increase in publication output over time. Selected findings are summarised in Box 3.

Raine eye health study: design, methodology and baseline prevalence of ophthalmic disease in a birth-cohort study of young adults.

ABSTRACT Purpose: The Raine Eye Health Study (REHS) was conceived to determine the prevalence of and risk factors for eye disease in young adults, and to characterize ocular biometric parameters in a young adult cohort. This article summarizes the rationale and study design of REHS and outlines the baseline prevalence of ophthalmic disease in this population. Methods: The Western Australian Pregnancy Cohort (Raine) Study originated as a randomized-controlled trial of 2900 women recruited from the state’s largest maternity hospital. Their offspring (N = 2868) have been followed at birth, ages 1, 2, 3, 5, 8, 10, 14, 17 and 20 years of age in a prospective cohort study. DNA has been collected from participants for genome-wide association studies. At the 20-year follow-up participants completed a comprehensive eye assessment that included visual acuity, orthoptic assessment and cycloplegic autorefraction, as well as several ocular biometric variables and multiple ophthalmic photographs of the anterior and posterior segments. Results: A total of 1344 participants (51.3% male) were assessed over a 24-month period. For the majority of examined participants (85.5%) both parents were Caucasian, 63.3% had completed school year 12 or equivalent, 5.5% had myopia (spherical equivalent ≤−3 diopters) and 15 participants (1.2%) had unilateral or bilateral pterygia. Keratoconus, cataract, keratitis and uveitis were rare. Conclusion: The REHS design and methodology allow comparison with other population-based studies of eye disease. The study established the prevalence of eye disorders in a large sample of predominantly Caucasian young Australian adults.

Pterygium and conjunctival ultraviolet autofluorescence in young Australian adults: the Raine study.

Sun exposure is associated with several ophthalmic diseases, including pterygium which may develop in adolescence. This study reports the prevalence of pterygium and its associations in a large cohort of young Australian adults. Conjunctival ultraviolet autofluorescence, a biomarker of ocular sun exposure, has recently been characterized in some Australian populations.

Genetic and environmental factors in conjunctival UV autofluorescence

IMPORTANCE Conjunctival UV autofluorescence (CUVAF) photography was developed to detect and characterize preclinical sunlight-induced ocular damage. Ocular sun exposure has been related to cases of pterygia and was recently negatively correlated with myopia. Hence, CUVAF has excellent potential as an objective biomarker of sun exposure. However, much variation in CUVAF has been observed, and the relative contributions of genes and environment to this variation have not yet been identified. OBJECTIVE To investigate sources of variation in CUVAF in relation to its potential clinical relevance. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional analysis of 3 population-based cohort studies in the general community, including the Twins Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Western Australian Pregnancy Cohort (Raine) Study. The twin studies were conducted between 2001 and 2009, and the 20-year follow-up of the Raine Study was completed between March 2010 and February 2012. We included genotypic and phenotypic data from 295 Australian families in the Tasmanian and Brisbane twin studies and from 661 participants in the 20-year follow-up of the Raine Study. We compared CUVAF levels in the 3 cohorts and performed a classic twin study to partition variation in CUVAF. We also conducted a genome-wide association analysis to identify specific genetic variants associated with CUVAF. MAIN OUTCOMES AND MEASURES The total area of CUVAF, heritability of CUVAF, and single-nucleotide polymorphisms (SNPs) associated with CUVAF from the genome-wide association study. RESULTS Within twin cohorts, individuals living closer to the equator (latitude, 27.47° S) had higher levels of CUVAF compared with individuals from southern regions (latitude, 42.88° S) (median [interquartile range], 45.4 [26.8-68.5] vs 28.7 [15.0-42.3] mm2; P < .001). The variation in CUVAF explained by the additive genetic component was 0.37 (95% CI, 0.22-0.56), whereas the variation due to the common environment was 0.50 (95% CI; 0.29-0.71). The SNP rs1060043, located approximately 800 base pairs away from the SLC1A5 gene, a member of the solute carrier family 1, had a genome-wide significant association with a P value of 3.2 × 10-8. Gene-based analysis did not improve our power to detect association with other genes. CONCLUSIONS AND RELEVANCE Our findings confirm that, although a large environmental component to CUVAF (equivalent of sun exposure) exists, genes also play a significant role. We identified a SNP (rs1060043) as being significantly associated with CUVAF; replication of this finding in future studies is warranted.

Brimonidine (Alphagan) associated anterior uveitis

Brimonidine is a well-recognised cause of ocular surface disease but is less widely known to cause uveitis. We present important clinical lessons from five new cases of brimonidine-associated anterior uveitis. 1. A 64-year-old man with primary open-angle glaucoma presented with red eyes and visual halos. He had used brimonidine 0.2%, timolol 0.5% and bimatoprost 0.03% for 13 months. There was bilateral anterior chamber inflammation with diffuse pigmented and stellate keratic precipitates. His intraocular pressure was 21 mm Hg bilaterally, rising to 26 mm Hg 3 weeks later. A trabeculectomy was planned, but cessation of brimonidine …

Comparison of monochromatic aberrations in young adults with different visual acuity and refractive errors.

Purpose To compare the monochromatic aberrations in a large cohort of 20‐year‐old Australians with differing levels of visual acuity and explore the relationship between these aberrations and refractive error. Setting Lions Eye Institute, Perth, Western Australia, Australia. Design Cross‐sectional analysis of a population‐based cohort. Methods Monochromatic aberrations were measured using a Zywave II wavefront aberrometer with natural pupils in a dark room. The logMAR corrected distance visual acuity (CDVA) was measured monocularly under normal illumination. Cycloplegic autorefraction was also performed. Results The study enrolled 2039 eyes of 1040 participants. Data from 1007 right eyes were analyzed. The median CDVA and spherical equivalent were −0.06 logMAR (interquartile range [IQR], −0.10 to 0.00) and +0.25 diopters (D) (IQR, −0.38 to 0.63), respectively. The median 6.0 mm higher‐order aberration (HOA) was 0.58 &mgr;m (IQR, 0.44 to 0.79). Coma‐like aberrations and 3rd‐, 4th‐, and 5th‐order HOAs were significantly different between subjects with a CDVA of −0.10 logMAR or better and those with a CDVA worse than −0.10 logMAR. Fourth‐order aberrations Z(4,−4) (P=.024) and Z(4,−2) (P=.029) and 2nd‐order aberration Z(2,0) (P<.001) differed significantly between myopic eyes, emmetropic eyes, and hyperopic eyes. Subjects with higher myopia had slightly higher total HOAs. Conclusions The HOAs in this population were marginally higher than previously reported values. The findings confirm there is a difference in monochromatic aberrations between different vision and refractive groups. Results in this study will benefit decision‐making processes in the clinical setting. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.