The Norfolk Island Eye Study (NIES): rationale, methodology and distribution of ocular biometry (biometry of the bounty).

AIM: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. METHODS: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. RESULTS: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. CONCLUSION: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Classification of iris colour: review and refinement of a classification schema.

Eye colour or, more accurately, iris colour is one of the most obvious physical characteristics of a person. European parents frequently ask the colour of their newborn's eyes, only to see the iris change dramatically during their child's first year of life. Genetic and epidemiological findings have uncovered further details about the basis for iris colour, which may have important implications for further research and treatment of some eye diseases and ocular characteristics. Surprisingly there is no widely recognized classification system for eye colour. An added difficulty when trying to devise an international system is that subtle differences in colour description exist between languages (e.g. hazel vs. auburn). We reviewed the recent and very early literature pertaining to eye colour classification. Recent genetic investigations of eye colour have tended to either use simple (three-category grading systems) or more complex digital colour grading. We present a nine-category grading system. Categories in this novel schema include: (i) light blue; (ii) darker blue; (iii) blue with brown peripupillary ring; (iv) green; (v) green with brown iris ring; (vi) peripheral green central brown; (vii) brown with some peripheral green; (viii) brown; and (ix) dark brown. Although different observers may categorize a person's eye colour differently, it is generally only by an adjacent category. We also describe a continuum of iris pigmentation from a small ring of brown around the pupil to almost complete brown with small peripheral flecks. Digital publishing and assessment of iris colour will result in more standardized classification of iris colour and investigation of its role in eye disease.

Don't it make your brown eyes blue? A comparison of iris colour across latitude in Australian twins.

BACKGROUND: The aim was to determine whether latitudinal (Queensland versus Tasmania) variation in reported disease frequency in Australia may be biased by differences in population. METHODS: A retrospective analysis was conducted from data of two large Australian twin studies (n = 1,835) having undertaken ophthalmic examination, namely, Twins Eye Study in Tasmania (TEST) and the Brisbane Adolescent Twins Study (BATS). Ordinal logistic regression was used to compute odds ratios and predicted probabilities for each category of eye colour by state. RESULTS: Tasmanian residence was associated with lower odds of darker iris colour (odds ratio 0.77, 95% CI [0.63-0.95]) signifying that participants living in Tasmania (TAS) are less likely to have darker-coloured irides than those residing in Queensland (QLD). For individuals living in Tasmania the predicted probability (TAS versus QLD) of having light blue eyes was greater (16.7 versus 13.3 per cent), approximately the same for green eyes and less for brown/dark brown-coloured eyes (6.2 versus 7.9 per cent). CONCLUSIONS: We found a general trend of individuals living in the southern states (TAS/VIC) of Australia having lighter-coloured irides compared to those living in the north (QLD). This finding has potential implications for all epidemiological research conducted to explore differences in UV-associated disease frequency in Australia, as population heterogeneity may confound the estimates obtained.

Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation.

OBJECTIVE: To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the myocilin mutation Thr377Met. METHOD AND DESIGN: Cross-sectional genetic study. Four unrelated pedigrees carrying the Thr377Met mutation were ascertained from more than 2000 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania and from families with glaucoma referred to the study from throughout Australia. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Thr377Met mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. RESULTS: From the 4 pedigrees carrying the Thr377Met mutation, 23 individuals with either ocular hypertension (OHT) or POAG were found, with a mean +/- SD age at diagnosis of 41.2 +/- 11.5 years, and a mean peak intraocular pressure of 31.7 +/- 9.9 mm Hg. A further 9 mutation carriers older than 18 years were studied who as yet showed no signs of OHT or POAG (6 of these 9 were younger than 30 years). A single individual with POAG was identified who did not carry the Thr377Met mutation. For Thr377Met carriers, age-related penetrance for OHT or POAG was 88% at age 30 years. A positive family history of POAG was present for 3 of the 4 index cases. Thirteen (57%) of the 23 Thr377Met carriers with OHT or POAG had undergone glaucoma drainage surgery. Although the glaucoma in these families appears to be pressure dependent, 2 individuals showed optic disc cupping before detected elevation in intraocular pressure. One family was of British origin, with a different background haplotype from the other 3 families from Greece or Macedonia, who shared a common haplotype. CONCLUSIONS: The GLC1A Thr377Met mutation is associated with POAG that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common Gln368STOP mutation. In addition, patients with glaucoma with the Thr377Met mutation were more likely to have undergone glaucoma drainage surgery.

Attitudes to predictive DNA testing for myocilin glaucoma: experience with a large Australian family.

PURPOSE: Glaucoma is a major cause of visual impairment and blindness in developed countries. Half of those with glaucoma are unaware that they have the disease. Mutations in the myocilin (MYOC) gene are responsible for 3 to 5% of primary open angle glaucoma, thus predictive DNA testing in family members of some glaucoma pedigrees is possible. We wished to determine the attitudes of affected and unaffected family members to the use of predictive DNA testing in glaucoma. SUBJECTS AND METHODS: We surveyed the attitudes of family members from one such pedigree to determine the acceptability of predictive DNA testing. We studied 72 members of a large family in which the MYOC mutation, THR377MET, segregates. Family members were examined over an 8-year period as part of research initiated to identify the gene. Once the mutation was identified, we offered participants the result of their DNA test after a genetic counseling session. Family members were subsequently given a questionnaire about the counseling and DNA result. RESULTS: Most wished to know their result after counseling; 26 of 27 (96%) felt the genetic counseling session was necessary, but participants' attitudes varied as to whether they preferred this in person, by phone, or letter. Forty three patients were resurveyed 5 years after their initial counseling session. No adverse problems relating to the predictive testing were reported, though two had been asked about DNA testing by insurance companies; 5 of 24 (21%) individuals who had been informed they did not carry the mutation were unsure if they carried the mutation 5 years after counseling, while all 19 mutation carriers (who were being examined annually) correctly recalled their mutation status. CONCLUSIONS: This study suggests that predictive glaucoma testing in appropriate circumstances is acceptable to patients and their families.

Tonography demonstrates reduced facility of outflow of aqueous humor in myocilin mutation carriers.

PURPOSE: To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography. MATERIALS AND METHODS: Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography. RESULTS: Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression; 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant. CONCLUSIONS: Carriers of the myocilin Thr377Met mutation have reduced outflow facility, which may be detected prior to developing glaucoma. Tonography was not seen to be clinically useful in predicting progression towards glaucoma.