Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

Early Anesthesia Exposure and the Effect on Visual Acuity, Refractive Error, and Retinal Nerve Fiber Layer Thickness of Young Adults.

OBJECTIVE: To investigate whether being anesthesia administered at least once in early life influenced 3 main proxies of visual function: visual acuity, refractive error, and optic nerve health in young adulthood. STUDY DESIGN: At age 20 years, participants of the Western Australian Pregnancy Cohort Study had comprehensive ocular examinations including visual acuity, postcycloplegic refraction, and multiple scans of the optic disc. We identified individuals who had at least 1 procedure requiring anesthesia during the first 3 years of life (between 1990 and 1994) and compared their visual outcomes with nonexposed individuals. We excluded 40 participants with strabismus or other ophthalmic disease or surgery and 136 with non-European background. RESULTS: Of 834 participants, 15.2% (n = 127) were exposed to anesthesia at least once before age 3 years. In both exposed and nonexposed groups, median visual acuity (measured using the logarithm of the minimum angle of resolution [LogMAR] chart) was -0.06 LogMAR in the right eye and -0.08 LogMAR in the left eye (P > .05). Median spherical equivalent refractive error was +0.44 diopters (IQR -0.25, +0.63) and +0.31 diopters (IQR -0.38, +0.63) in the exposed and nonexposed group, respectively (P = .126). No difference was detected in mean global retinal nerve fiber layer thickness of the 2 groups (100.7 vs 100.1 µm, P = .830). CONCLUSIONS: We were unable to demonstrate an association of exposure to anesthesia as a child with reduced visual acuity or increased myopia or thinning of retinal nerve fiber layer. These findings support the view that anesthesia is unlikely to impair visual development, but further work is needed to establish whether more subtle defects are present and repeated exposures have any effects.

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

BACKGROUND: 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. DESIGN: Cross-sectional population-based study. PARTICIPANTS: One thousand three hundred forty-four subjects aged 18-22 years in the Western Australian Pregnancy Cohort (Raine) Study. METHODS: Standardized colour and ultraviolet autofluorescence photographs of the nasal and temporal conjunctiva were taken, and assessed for presence of pterygium and area of autofluorescence. Sun exposure and protective factors were assessed by structured questionnaire. MAIN OUTCOME MEASURES: Area of conjunctival ultraviolet autofluorescence in square millimetre (mm(2)) and presence of pterygium. RESULTS: Median total conjunctival autofluorescence was 44.2 mm(2) (interquartile range 20.2-69.8 mm(2)). Median conjunctival autofluorescence was higher in nasal than in temporal quadrants (23.8 mm(2) vs. 18.9 mm(2), P < 0.001), but did not differ according to age or gender. Higher body mass index was associated with lower levels of autofluorescence. Total autofluorescence increased with increasing time spent outdoors. Prevalence of pterygium was 1.2% (95% confidence interval 0.6-1.8%), and was associated with male gender (odds ratio 6.71, P = 0.012). Participants with pterygium had significantly more conjunctival autofluorescence than those without (median 73.4 mm(2) vs. 44.0 mm(2), P = 0.001). CONCLUSIONS: Conjunctival ultraviolet autofluorescence is associated with increased time spent outdoors, and increased prevalence of pterygium. The association of this biomarker with other ophthalmohelioses, including cataract, ocular surface squamous neoplasia and eyelid malignancy, has yet to be determined.

Missing X and Y: a review of participant ages in population-based eye studies.

Ophthalmic population-based studies have been used to establish the frequency of eye disease and the associated environmental and genetic factors that cause vision impairment and blindness. Most of these studies have concentrated on the diseases of ageing: cataract, age-related macular degeneration, glaucoma and diabetic retinopathy. Other studies have identified eye diseases in children but few studies of young adult eye disease exist. We conducted a systematic review of the ophthalmic literature to identify potential population-based eye studies and then note the age of participants in the studies. We then summarized the disease specific to young adults to show there is a need for further research to identify eye disease in this important and often-neglected group in the community. Eighty-four large population-based studies have been conducted worldwide: 9 in North America, 2 in South America, 17 in Africa, 35 in Asia, 11 in Australia and the Pacific, 6 in Europe, 4 in the Middle East and 1 that covered 3 continents. No studies specifically examined young adults. Twenty-six per cent of studies included young adults as part of all ages examined but none of these examined a large number of young adults.

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 µm (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.

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.

Birth order and myopia.

PURPOSE: An association between birth order and reduced unaided vision (a surrogate for myopia) has been observed previously. We examined the association between birth order and myopia directly in four subject groups. METHODS: Subject groups were participants in (1) the Avon Longitudinal Study of Parents and Children (ALSPAC; UK; age 15 years; N = 4401), (2) the Singapore Cohort Study of Risk Factors for Myopia (SCORM; Singapore; age 13 years; N = 1959), (3) the Raine Eye Health Study (REHS; Australia; age 20 years; N = 1344), and (4) Israeli Defense Force Pre-recruitment Candidates (IDFC; Israel; age 16-22 years; N = 888,277). The main outcome was odds ratios (OR) for myopia in first-born versus non-first-born individuals after adjusting for potential risk factors. RESULTS: The prevalence of myopia was numerically higher in first-born versus non-first-born individuals in all study groups, but the strength of evidence varied widely. Adjusted ORs (95% confidence intervals, CIs) were: ALSPAC, 1.31 (1.05-1.64); SCORM, 1.25 (0.89-1.77); REHS, 1.18 (0.90-1.55); and IDFC, 1.04 (1.03-1.06). In the large IDFC sample, the effect size was greater (a) for the first-born versus fourth- or higher-born comparison than for the first-born versus second/third-born comparison (p < 0.001) and (b) with increasing myopia severity (p < 0.001). CONCLUSIONS: Across all studies, the increased risk of myopia in first-born individuals was low (OR < 1.3). Indeed, only the studies with >4000 participants provided strong statistical support for the association. The available evidence suggested the relationship was independent of established risk factors such as time outdoors/reading, and thus may arise through a different causal mechanism.

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

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.

Twenty-five years of treatment for childhood acute lymphoblastic leukaemia in Western Australia: how do we compare?

OBJECTIVES: To compare survival among the subgroup of children with acute lymphoblastic leukaemia (ALL) who were treated at Princess Margaret Hospital for Children (PMH) in Perth, Western Australia, over 25 years under 15 consecutive protocols of the Children's Cancer Group (CCG) with survival for the entire cohort of children in multiple centres treated under CCG protocols in that period; and to highlight the benefits of membership of a large cooperative research group conducting multicentre randomised controlled trials. DESIGN, PARTICIPANTS AND SETTING: Retrospective review of the outcomes of all 311 children with newly diagnosed ALL treated at PMH between 1983 and 2008. MAIN OUTCOME MEASURES: 4-year event-free survival; and 10-year overall survival. RESULTS: Four-year event-free survival for the entire PMH cohort increased from 66% (SE, 6%) for 1983-1987 to 88% (SE, 6%) for 2002-2005, while overall survival over the same period improved from 78% (SE, 5%) to 94% (SE, 4%). Comparisons of outcomes of children treated at PMH with those of the entire CCG cohort, protocol by protocol, revealed similar outcomes. CONCLUSION: Outcomes of children treated at PMH over the 25-year period are equivalent to those of the larger CCG cohort.