Screening for glaucomatous disc changes prior to diagnosis of glaucoma in myocilin pedigrees.

OBJECTIVE: To investigate whether structural differences of the optic nerve head are evident in young people who do not have manifest glaucoma but are known to carry myocilin mutations. METHODS: A case-control design was adopted. Subjects from Australian pedigrees known to have either the Gln368STOP myocilin mutation (cutoff age, <40 years) or the Thr377Met myocilin mutation (cutoff age, <30 years) were examined for signs of glaucoma. Stereoscopic disc photographs were digitalized. Analysis of the optic disc area, optic cup area, and neuroretinal rim area was performed using digital stereoscopy with a Z-screen. Mutation analysis was conducted using direct sequencing. The t test, corrected for multiple comparison testing, was used in analysis. RESULTS: A total of 29 myocilin mutation-carrying (case) and 33 mutation-free (control) individuals were reviewed. The mean +/- SD ages were 19.9 +/- 9.0 and 22.1 +/- 9.5 years in the mutation and mutation-free groups, respectively (P = .35). There was no significant difference in intraocular pressure between mutation carriers and noncarriers (P = .44). There were no statistically significant differences in the mean disc, neuroretinal rim, and cup areas between the groups. The mean +/- SD neuroretinal rim area was 1.24 +/- 0.24 mm(2) in the noncarrier group and 1.25 +/- 0.23 mm(2) in the mutation group (P = .46). No notch, nerve fiber layer defect, or neuroretinal rim hemorrhage was noted in any eye examined. CONCLUSIONS: Although confounded by penetrance and expressivity, no quantified structural difference in the optic nerve head was observed in individuals who had a myocilin mutation prior to the diagnosis of glaucoma.

Central corneal thickness is highly heritable: the twin eye studies.

PURPOSE: A classic twin study was performed to determine the heritability of central corneal thickness (CCT), an important parameter in glaucoma assessment. METHODS: The concordance of CCT between monozygotic (MZ) and dizygotic (DZ) twins was compared. A total of 256 twin pairs (131 MZ and 125 DZ) were recruited from three centers: the Twin Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Twins U.K. Adult Registry held at St. Thomas' Hospital in London. As part of an extensive ophthalmic evaluation, CCT was measured by ultrasound pachymetry. Structural equation modeling with the Mx program (Department of Psychiatry, Medical College of Virginia, Richmond, VA) was used to determine the heritability of CCT. RESULTS: The mean age of subjects was 38 years (range, 8-81). The mean CCT of all eyes examined was 544.5 +/- 37.3 mum (SD). The CCT measurements correlated more highly in MZ twins than in DZ twins, with intraclass correlation coefficients of 0.95 and 0.52, respectively, suggesting a strong genetic influence. A model of additive genetic and unique environmental effects provided the best fit, yielding a heritability of 0.95 (95% confidence interval [CI], 0.93-0.96) with the remaining variation being attributable to unique environmental factors. CONCLUSIONS: In this study of Australian and U.K. twins, genetic factors were shown to be of major importance in CCT, with a heritability of 0.95.

Digital stereoscopic analysis of the optic disc: evaluation of a teaching program.

PURPOSE: To determine if a computer-based stereoscopic teaching program could improve optic cup/disc ratio (CDR) agreement between student observers and an expert. DESIGN: Experimental study. PARTICIPANTS: Six student observers (A-F) assessed at least 30 digital stereoscopic optic disc images using a digital stereoscopic analysis program. All observers made 36 CDR measurements (every 10 degrees ) for each disc image that they assessed. METHODS: Disc images were divided into 3 sets of 10 images (image sets 1, 2, and 3). Observers A, B, and C determined CDRs for all 3 image sets. Set 1 was examined without access to a teaching program, set 2 using a teaching program that allowed the observer to view an expert assessment of the optic disc, and set 3 after using the teaching program. Observers D, E, and F evaluated image sets 1 and 3 only and did not have access to the teaching program. Ten months later, these same observers (D-F) viewed image set 2 using the teaching program and then reassessed image set 3. MAIN OUTCOME MEASURES: Standard deviation (SD) of CDR differences between observers and an expert, the percentage of CDR observations differing > or =0.20 from those of the expert, and intraclass correlation coefficients (ICCs) between observers. RESULTS: Before teaching, the average SD of differences between all observers and the expert was 0.10. After teaching, the average SD of differences between all observers and the expert was 0.057. For observers D, E, and F, the average SD of differences for image set 3 without teaching was 0.074. The percentage of all observer measurements that differed > or =0.20 from those of the expert for image set 1 was 16.7%; for set 3 after teaching, 1.7%; and for set 3 for observers D, E, and F without teaching, 10%. Interobserver ICC values for all observers were 0.37 before teaching and 0.76 after. For observers D, E, and F, the ICC value for set 3 without access to teaching was 0.69. CONCLUSIONS: This study suggests that an interactive digital stereoscopic teaching program improves agreement between observers and an expert when assessing CDRs.

Are Duane syndrome and infantile esotropia allelic?

PURPOSE: To evaluate the clinical overlap of families with Duane syndrome and infantile esotropia to determine whether the identification of genes for Duane syndrome may explain some cases of infantile esotropia. METHODS: Three separate groups of patients were evaluated. 1) Families with features of infantile esotropia were identified through the Strabismus Inheritance Study Tasmania (SIST). Clinical details of participants and their families were reviewed for any cases of Duane syndrome. 2) Cases of Duane syndrome were identified through the clinical diagnostic database at the Royal Children's Hospital, Melbourne, and private ophthalmology clinics in Melbourne and Tasmania. Previous medical notes were reviewed and family history of strabismus noted. All affected individuals were invited for re-examination in cases where a positive family history of strabismus was reported; siblings, parents, and other family members, where appropriate, were invited to be examined for signs of Duane syndrome or infantile esotropia. 3) Cases of mosaic trisomy 8, which has been associated with Duane syndrome and infantile esotropia, were reviewed for signs of strabismus. RESULTS: A total of 133 families from the SIST were reviewed, but no 'pure' families of Duane syndrome were identified. Two families with infantile esotropia had several members affected with Duane syndrome. Of the 40 index cases with Duane syndrome whose families agreed to be involved in the study, 21 had a family history of ocular motility disorders, but only two of these families had multiple cases of Duane syndrome. From 24 cases with mosaic trisomy 8, one individual case had Duane syndrome and another had mild congenital cataracts and infantile esotropia. CONCLUSIONS: There is clinical overlap in families with Duane syndrome and infantile esotropia. We confirmed the previous association of mosaic trisomy 8 with both Duane syndrome and infantile esotropia. These data suggest that the two conditions may be allelic and may be due to a gene on chromosome 8.