Age
The depth and volume of the anterior chamber decrease with age. These changes predispose the eye to pupillary block; thus, the prevalence of angle-closure glaucoma with pupillary block increases with age. Acute angle-closure glaucoma is most common between the ages of 55 and 65 years, but it can occur in young adults and has been reported in children.
Refraction
Although PACG may occur hyperopia. The depth and predisposing them to PACG.
in eyes with any type of refractive error, it is typically associated with volume of the anterior chamber are reduced in hyperopic eyes,
Inheritance
Some of the anatomical features of the eye that predispose to pupillary block, such as a more anterior lens position and greater-than-average lens thickness, are inherited. Although generalizable estimates are lacking, a population-based survey in China suggests that a family history of glaucoma increases the risk of PACG sixfold.
Epstein DL, Allingham RR, Schuman JS, eds. Chandler and Grant’s Glaucoma. 4th ed. Baltimore: Williams & Wilkins; 1997:641– 646.
Ritch RM, Shields MB, Krupin T, eds. The Glaucomas. 2nd ed. St Louis: Mosby; 1996:753–765.
Genetics, Environmental Factors, and Glaucoma
The precise mechanism of inheritance of glaucoma is not clear. To date, many of the glaucomas appear to have an autosomal dominant inheritance pattern that may involve more than 1 gene (polygenic); have a late or variable age of onset; demonstrate incomplete penetrance (ie, the disease may not develop even when the causative gene has been inherited); and may be substantially influenced by environmental factors. See also BCSC Section 2, Fundamentals and Principles of Ophthalmology, Part III, Genetics. A positive family history is a risk factor for the development of POAG. The prevalence of glaucoma among siblings of glaucoma patients is approximately 10%.
The first gene described for POAG, GLC1A (also called the trabecular meshwork inducible glucocorticoid response/myocilin gene [TIGR/MYOC]), codes for the TIGR protein and is a trabecular meshwork glucocorticoid gene, located on chromosome 1. Mutations in GLC1A are present in 3% of the general open-angle glaucoma population. In the mid-1990s, the gene responsible for mutations in the TIGR protein was identified. Since then, several additional open-angle glaucoma genes have been mapped, and many more potential genes are being explored. The percentage of genes known to be associated with specific types of glaucoma is small, most likely because of the complex nature of the disease and because of the complicated interactions between multiple genetic loci and environmental factors (Table 1-4). Researchers are increasingly applying genome-wide scanning techniques to large cohorts of glaucoma subjects. These techniques may be useful for determining which regions of the genome are associated with glaucoma.
Kass MA, Becker B. Genetics of primary open-angle glaucoma. Sight Sav Rev. 1978;48:21–28.
Polansky JR, Fauss DJ, Chen P, et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica. 1997;211(3):126–139.
Stone EM, Fingert JH, Alward WL, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275(5300):668–670.
Wolfs RC, Klaver CC, Ramrattan RS, van Duijn CM, Hofman A, de Jong PT. Genetic risk of primary open-angle glaucoma: population-based familial aggregation study. Arch Ophthalmol. 1998;116(12):1640–1645.
Table 1-4
Environmental Factors
Evidence that environmental factors can also play a role in the etiology of glaucoma arises from studies of twins and analysis of the season of birth of glaucoma patients. If glaucoma is genetically determined, then identical twins should theoretically share this trait more often than fraternal twins. In the Finnish Twin Cohort Study, 3 of 29 monozygotic twin pairs were concordant for POAG, compared with 1 of 79 dizygotic twin pairs. Although a higher percentage of monozygotic twins were concordant for glaucoma, most were not. These data suggest that although genetic factors contribute to the etiology of glaucoma, other factors, such as environmental influences, are important.
Genetic Testing
In the future, the management of some glaucoma patients will involve testing of multiple, and potentially interacting, genetic loci. Although there have been rapid advances in genetic techniques that allow this type of testing, advances in the study of genetic diseases require accurate categorization of individuals and families with specific phenotypes. By appropriately identifying families with strong histories of glaucoma, the practicing clinical ophthalmologist has an opportunity to provide important information to researchers in genetics. The cooperation of the clinician is therefore critical to the advancement of this crucial area of research.
The reader is encouraged to review the literature and to refer to websites such as GeneTests for information on genetic testing and its use in diagnosis, management, and genetic counseling (http://w ww.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests).
Thorleifsson G, Magnusson KP, Sulem P, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397–1400.