A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.

Purpose To determine the relative efficacy and complications of the Ahmed FP7 Glaucoma Valve (AGV) and the Baerveldt 101–350 Glaucoma Implant (BGI) in refractory glaucoma. Design Multicenter randomized controlled clinical trial. Participants 276 patients, including 143 in the AGV group and 133 in the BGI group. Methods Patients aged 18–85 years with refractory glaucoma with intraocular pressure (IOP) greater than or equal to 18 mm Hg in whom an aqueous shunt was planned were randomized to undergo implantation of either an AGV or a BGI. Main Outcome Measures Primary outcome was failure, defined as IOP > 21 mm Hg or not reduced by 20%, IOP ≤ 5 mm Hg, reoperation for glaucoma or removal of implant, or loss of light perception vision. Secondary outcomes included mean IOP, visual acuity, use of supplemental medical therapy, and complications. Results Preoperative IOP (mean ± standard deviation, SD) was 31.2 ± 11.2 in the AGV group and 31.8 ± 12.5 in the BGI group (p = 0.71). At 1 year, IOP was 15.4 ± 5.5 mm Hg in the AGV group and 13.2 ± 6.8 mm Hg in the BGI group (p = 0.007). The number of glaucoma medications (mean ± SD) was 1.8 ± 1.3 in the AGV group and 1.5 ± 1.4 in the BGI group (p = 0.071). The cumulative probability of failure was 16.4% (standard error, SE = 3.1%) in the AGV group and 14.0% (SE = 3.1%) in the BGI group at 1 year (p = 0.52). More patients experienced early postoperative complications in the BGI group (n = 77, 58%) compared to the AGV group (n = 61, 43%, p = 0.016). Serious postoperative complications associated with reoperation and/or vision loss of ≥ 2 Snellen lines occurred in 29 patients (20%) in the AGV group and 45 patients (34%) in the BGI group (p = 0.014). Conclusions Although the average IOP after one year was slightly higher in patients who received an AGV, there were fewer early and serious postoperative complications associated with the use of the AGV than the BGI.

"Early-onset glaucoma" refers to genetically heterogeneous conditions for which glaucoma manifests at age 5-40 years and for which only a small subset is molecularly characterized. We studied the role of MYOC, CYP1B1, and PITX2 in a population (n=60) affected with juvenile or early-onset glaucoma from the greater Toronto area. By a combination of single-strand conformation polymorphism and direct cycle sequencing, MYOC mutations were detected in 8 (13.3%) of the 60 individuals, CYP1B1 mutations were detected in 3 (5%) of the 60 individuals, and no PITX2 mutations were detected. The range of phenotypic expression associated with MYOC and CYP1B1 mutations was greater than expected. MYOC mutations included cases of juvenile glaucoma with or without pigmentary glaucoma and mixed-mechanism glaucoma. CYP1B1 mutations involved cases of juvenile open-angle glaucoma, as well as cases of congenital glaucoma. The study of a family with autosomal dominant glaucoma showed the segregation of both MYOC and CYP1B1 mutations with disease; however, in this family, the mean age at onset of carriers of the MYOC mutation alone was 51 years (range 48-64 years), whereas carriers of both the MYOC and CYP1B1 mutations had an average age at onset of 27 years (range 23-38 years) (P=.001). This work emphasizes the genetic heterogeneity of juvenile glaucoma and suggests, for the first time, that (1) congenital glaucoma and juvenile glaucoma are allelic variants and (2) the spectrum of expression of MYOC and CYP1B1 mutations is greater than expected. We also propose that CYP1B1 may act as a modifier of MYOC expression and that these two genes may interact through a common pathway.