Predictive DNA testing for glaucoma: reality in 2003

David A. Mackay, Jamie E. Craig

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


As new genes and common mutations are identified, DNA testing can be offered. Like clinical testing used in glaucoma, such as IOP, tonography, disc measurements, nerve fiber layer analysis, and the various methods of visual field analysis, well-designed studies are needed to be able to interpret clearly the meaning of abnormal results. To use DNA testing to identify individuals at high risk for glaucoma, it is necessary to have solid evidence with sensitivity and specificity parameters, genotype-phenotype correlations, and information on prevalence and penetrance. These data will have to be replicated in several studies using large, population-matched control groups. Mass screening of glaucoma patients for Myocilin mutations may be worthwhile if 3% to 5% of glaucoma patients will be positive. For comparison, screening all cases of colon cancer for gene mutations involved in hereditary nonpolyposis colorectal cancer is considered feasible and desirable with a yield of only 3%. Recent research has shown the value of early treatment of glaucoma. The cost effectiveness of genetics screening will need to be weighed against the cost of conventional screening and the benefits of early treatment considered. Within glaucoma pedigrees with known mutations, DNA mutation-positive individuals will need more frequent clinical screening, whereas DNA mutation-negative individuals will need less frequent follow-up. It is likely that, for every positive-mutation glaucoma case identified, there will be on average two siblings and two children to test. In addition to the laboratory costs, the costs of counseling, and, in particular, the availability of suitably trained individuals who can correctly interpret these test results, must be considered. The risk and benefits of these measures must be calculated and then balanced with the long-term visual outcome of such a strategy. How could genetic testing alter management in glaucoma? If a family member in a Myocilin pedigree with a severe mutation is negative for the mutation, that individual's risk changes from 50% to that of the general population (ie, -2%), and the frequency of clinical screening can be reduced. There are ethical issues involved in testing, particularly in children, but testing would seem justified in congenital, developmental, and juvenile glaucoma. Issues related to insurance may affect the decision making of some patients. A further consideration, which may regrettably become important in the future, is that of intellectual property and patent issues pertaining to glaucoma gene discovery. In addition to clinical evidence of the value of predictive DNA testing, it is incumbent on those working in the field to evaluate the acceptability of testing to patients and their family members. The authors' experience to date is that predictive DNA testing in glaucoma is well supported in suitable families. As with predictive DNA screening in other ophthalmic conditions, issues relating to insurance, ethics, and confidentiality need to be taken into consideration. Although many of the more recently described genetic associations of POAG require more thorough evaluation, Myocilin gene testing can and should be offered for young-onset severe glaucoma cases with a positive family history.
Original languageEnglish
Pages (from-to)639-645
Number of pages7
JournalOphthalmology Clinics of North America
Issue number4
Publication statusPublished - Dec 2003


  • DNA testing
  • gene mutations


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