A Case-control Comparison of the Clinical Characteristics of Glaucoma and Ocular Hypertensive Patients With and Without the Myocilin Gln368Stop Mutation THOMAS A. GRAUL, MD, YOUNG H. KWON, MD, PHD, M. BRIDGET ZIMMERMAN, PHD, CHANG-SIK KIM, MD, VAL C. SHEFFIELD, MD, PHD, EDWIN M. STONE, MD, PHD, AND WALLACE L. M. ALWARD, MD ● PURPOSE: To determine whether primary open-angle glaucoma (POAG) and ocular hypertensive (OHT) pa- tients who harbor the myocilin Gln368Stop mutation differ in phenotype or clinical course from patients without the mutation. ● DESIGN: Case-control study. ● METHODS: A retrospective case-control study com- pared all known POAG patients (n  18) and OHT patients (n  4) harboring the Gln368Stop mutation evaluated by the University of Iowa Glaucoma Service with control patients from the same population. Patients and control subjects were matched for diagnosis, age, sex, and race and were compared for phenotype and clinical course. ● RESULTS: Mean age of disease onset and mean peak intraocular pressures (IOPs) of cases were similar to those reported by other studies. There was no statisti- cally significant difference between cases and controls for the following variables: age at onset, peak intraocular pressure, Snellen visual acuity, number of medications, Humphrey visual field (HVF) mean deviation, HVF pattern deviation, number of filtering surgeries per- formed, time intervals from diagnosis to argon laser trabeculoplasty (ALT), diagnosis to first filtering sur- gery, ALT to first filtering surgery, and percent change in IOP after ALT and after first filtering surgery. ● CONCLUSIONS: There is no statistically significant difference between the onset and clinical course of POAG and OHT caused by the Gln368Stop mutation and POAG and OHT not associated with the mutation. (Am J Ophthalmol 2002;134:884 – 890. © 2002 by Elsevier Science Inc. All rights reserved.) P RIMARY OPEN-ANGLE GLAUCOMA (POAG) IS THE most common form of glaucoma and is a leading cause of blindness worldwide. 1,2 In addition to ad- vanced age, African ancestry, and ocular hypertension (OHT), a family history of glaucoma is a major risk factor for this disease. 3 For patients with a positive family history in a parent or sibling, the risk of developing glaucoma is as much as eight times higher than for the general popula- tion. 3 For most patients, POAG appears to be inherited in a non-Mendelian fashion, although pedigrees have been reported with clear autosomal dominant and recessive patterns. 4–7 The discovery of the first gene for adult-onset POAG began with a linkage analysis study of a large family with juvenile-onset POAG. 8,9 Autosomal dominant juvenile- onset POAG is an uncommon form of glaucoma charac- terized by onset early in life, open angles with a normal appearing trabecular meshwork, high intraocular pressures (IOP), and autosomal dominant inheritance with high penetrance. 8 A locus on chromosome 1q was associated with this disease and was named GLC1A. 9 A candidate gene, myocilin (then known as the trabecular meshwork glucocorticoid receptor protein, or TIGR) was found to reside in this interval, and mutations in the linked gene were subsequently shown to cause most cases of autosomal Accepted for publication July 22, 2002. Internet Advance publication at ajo.com Sept 6, 2002. From the Department of Ophthalmology and Visual Sciences (T.A.G., Y.H.K., C.-S.K., E.M.S., W.L.M.A.), College of Medicine, the Depart- ment of Biostatistics (M.B.Z.), College of Public Health, and the Department of Pediatrics (V.C.S.), College of Medicine, University of Iowa, Iowa City, Iowa, and Howard Hughes Medical Institute, Iowa City, Iowa. This study was presented in part at the Annual Meeting of the American Glaucoma Society, San Juan, Puerto Rico, March 1, 2002. This work was supported by Grant EY-10564 from the National Institutes of Health, Bethesda, Maryland, and in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Inquiries to Wallace L. M. Alward, MD, Department of Ophthalmol- ogy and Visual Sciences, University of Iowa College of Medicine, 200 Hawkins Dr, Iowa City, IA 52242; fax: (319) 353-7699; e-mail: wallace- alward@uiowa.edu © 2002 BY ELSEVIER SCIENCE INC.ALL RIGHTS RESERVED. 884 0002-9394/02/$22.00 PII S0002-9394(02)01754-3