The ocular hypertension treatment study: intraocular pressure lowering prevents the development of glaucoma, but does that mean we should treat before the onset of disease?

W E WOULD LIKE to congratulate Kass et al and Gordon et al for their 2 well-written articles concerning a well-designed and important study. They clearly demonstrate that medical therapy that lowers intraocular pressure (IOP) prevents or retards the development of glaucoma in patients with ocular hypertension. This is noteworthy as it links the development of glaucoma to IOP lowering for the first time in a conclusive manner. This helps us better understand the glaucomatous process when combined with the results of other multicentered studies that find IOP lowering can retard the progression of glaucoma at various stages of the disease process. The critical question is how to apply this information in clinical practice and policy making. Kass et al and Gordon et al find that medical treatment halves the development of the earliest detectable glaucoma damage given our current techniques. At 60 months, only 4.4% of treated patients compared with 9.5% of untreated patients develop glaucoma. If we look at one of the higher-risk groups, those patients whose IOPs were higher than 25.75 mm Hg and had corneal thicknesses less than 555 μm had a 36% chance of developing glaucoma in 5 years without treatment. Conversely, 64% of these relatively highrisk patients will not develop damage in a 5-year period. Kass et al then conclude that “clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG [primary openangle glaucoma].” We believe that this recommendation requires further consideration. Recent multicentered clinical trials have only dealt with a smaller proportion of the population that already has a disease. Intraocular pressure lowering in these people has been shown to retard glaucomatous progression in those afflicted. The Ocular Hypertension Treatment Study results affect a large percentage of the US population. The number of patients with ocular hypertension is large, and most of those will not develop visual-field loss. So, the issue is whether all these people should be treated. Almost 8% (7.4%) of eyes have IOPs higher than 21 mm Hg on a single eye examination but do not have POAG as defined by optic nerve damage consistent with POAG. If we consider an IOP higher than 24 mm Hg, the proportion of the population without glaucoma is 3.5%. The implications of these Ocular Hypertension Treatment Study articles affect many patients and the physicians who must make rational decisions based on the data in these articles. We must consider the benefits and costs of therapy, adverse effects of therapies, and quality of life issues before a plan of action is made. Glaucoma is a serious, irreversible but slowly progressive disease. Because the disease affects the peripheral visual field first, it is usually many years from the onset of disease to functional visual loss unless the IOP is higher than the range studied in the Ocular Hypertension Treatment Study. Even using standard achromatic automated static perimetry, the physician can detect visual-field defects below the level of the defect from the physiologic blind spot, which we all live with and have no symptoms. Given the cost of treating all people with ocular hypertension at moderate to high risk of developing glaucoma, it may still be reasonable to wait until the earliest change in the optic nerve or visual field is detected. Contrary to clinical perceptions, glaucoma progresses so slowly that most patients die before developing blindness, even in one eye. Quigley et al found that it takes 13 years for white individuals and 16 years for African American individuals to go blind from glaucoma. It appears to take 40 years for someone with visual-field loss at age 40 to become legally blind in one eye and develop visual-field loss in the fellow eye. In cross-sectional data using the Baltimore Eye Study, the Beaver Dam Eye Study, and the Framingham Eye Study, only 4% of white individuals and 8% of African American individuals with glaucoma are legally blind from it. Also, there is little evidence of an effect on healthrelated quality of life until the disEditor’s Note