Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry.

PURPOSE: To report the relative frequencies of childhood and early onset glaucoma subtypes and their genetic findings in a large single cohort. DESIGN: Retrospective clinical and molecular study. PARTICIPANTS: All individuals with childhood glaucoma (diagnosed 0 to <18 years) and early onset glaucoma (diagnosed 18 to <40 years) referred to a national disease registry. METHODS: We retrospectively reviewed the referrals of all individuals with glaucoma diagnosed at <40 years of age recruited to the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG). Subtypes of glaucoma were determined using the Childhood Glaucoma Research Network (CGRN) classification system. DNA extracted from blood or saliva samples underwent sequencing of genes associated with glaucoma. MAIN OUTCOME MEASURES: The phenotype and genotype distribution of glaucoma diagnosed at <40 years of age. RESULTS: A total of 290 individuals (533 eyes) with childhood glaucoma and 370 individuals (686 eyes) with early onset glaucoma were referred to the ANZRAG. Primary glaucoma was the most prevalent condition in both cohorts. In the childhood cohort, 57.6% of individuals (167/290, 303 eyes) had primary congenital glaucoma (PCG), and 19.3% (56/290, 109 eyes) had juvenile open-angle glaucoma. Juvenile open-angle glaucoma constituted 73.2% of the early onset glaucoma cohort (271/370, 513 eyes). Genetic testing in probands resulted in a diagnostic yield of 24.7% (125/506) and a reclassification of glaucoma subtype in 10.4% of probands (13/125). The highest molecular diagnostic rate was achieved in probands with glaucoma associated with nonacquired ocular anomalies (56.5%). Biallelic variants in CYP1B1 (n = 29, 23.2%) and heterozygous variants in MYOC (n = 24, 19.2%) and FOXC1 (n = 21, 16.8%) were most commonly reported among probands with a molecular diagnosis. Biallelic CYP1B1 variants were reported in twice as many female individuals as male individuals with PCG (66.7% vs. 33.3%, P = 0.02). CONCLUSIONS: We report on the largest cohort of individuals with childhood and early onset glaucoma from Australasia using the CGRN classification. Primary glaucoma was most prevalent. Genetic diagnoses ascertained in 24.7% of probands supported clinical diagnoses and genetic counseling. International collaborative efforts are required to identify further genes because the majority of individuals still lack a clear molecular diagnosis.

Validity and repeatability of contour-based visotec distance stereoacuity test.

CLINICAL RELEVANCE: The clinical assessment of distance stereoacuity is important in some ocular conditions. Given the different neurophysiological mechanism for crossed and uncrossed stereoacuities, evaluation of both may provide additional insight into binocular vision disorders. BACKGROUND: Clinical devices measuring distance crossed and uncrossed stereopsis are not readily available. Visotec Distance Stereo Test (VDST) is a contour-based device designed to measure both forms of distance stereoacuity. This study assesses the validity and test-retest reliability of the device in comparison to the random dot-based Randot Distance Stereo Test (RDST). METHOD: VDST and RDST were administered to a total of 107 children, that included 51 'normal' and 56 'abnormal' (37 intermittent exotropia and 19 amblyopia) between the ages of 5 and 15 years. Two examiners retested stereoacuities in a sub-set of 62 randomly selected subjects. Stereoacuity was transformed to log scale. 95% limits of agreement were calculated for test-retest reliability. The Bland-Altman plot was used to demonstrate the agreement between the tests and the examiners. RESULTS: The mean ± SD crossed distance stereoacuities using VDST in normal, intermittent exotropia and amblyopic children were 93.1 ± 43.8, 161.9 ± 89.8 and 236.3 ± 122.4 arcseconds, respectively. For uncrossed stereoacuity, these were 104.7 ± 54.0, 187.6 ± 89.6 and 265.5 ± 144.0 arcseconds, respectively. Crossed stereoacuity was significantly better than uncrossed stereoacuity. 95% limits of test-retest agreement for crossed and uncrossed stereoacuities using the VDST were 0.27 and 0.30, respectively. An exact test-retest match using VDST was 84% in normals and 77% in abnormals for crossed and 83% in normal and 74% in abnormal for uncrossed stereoacuities. CONCLUSION: VDST is a reliable, valid and easy-to-administer distance crossed and uncrossed stereoacuity measuring device. Further studies are required to establish the clinical importance of assessing these two forms stereoacuities in relation to various binocular vision disorders.