Ocular Hypertension

In this book, ocular hypertension is defined as a condition in which IOP is elevated above an arbitrary cutoff value, typically 21 mm Hg, in the absence of optic nerve, retinal nerve fiber layer, or visual field abnormalities. This condition is discussed in its own section given the availability of high-quality clinical trial data that are not available for other categories of glaucoma suspects. Estimates of the prevalence of ocular hypertension in the United States vary considerably and may be as high as 8 times that of diagnosed POAG. Studies of individuals with elevated IOP for various lengths of time suggest that a higher baseline IOP is associated with a greater risk of developing glaucoma. However, for most persons with elevated IOP, the risk of developing glaucoma is low.

Distinguishing between ocular hypertension and early POAG is often difficult. The ophthalmologist must look carefully for signs of early damage to the optic nerve, such as focal notching, asymmetry of cupping, optic disc hemorrhage, nerve fiber layer defects, or subtle visual field defects.

There is no clear consensus about whether elevated IOP should be treated in the absence of signs of early damage. Some clinicians, after assessing all risk factors, select and treat those individuals thought to be at greatest risk of developing glaucoma. In the OHTS, patients 40–80 years of age with IOP between 24 and 32 mm Hg were randomized to either observation or treatment with topical ocular hypotensive medications (see Clinical Trial 7-2 at the end of this chapter). During a 5-year period, 4.4% of participants in the treatment group versus 9.5% of participants in the observation group progressed to glaucoma as determined by optic nerve or visual field changes. Thus, topical medications reduce the risk of progression to glaucoma in patients with ocular hypertension. It should be noted, however, that most untreated participants did not progress over a 5-year period. In the OHTS, the risk of developing glaucoma was increased by 10% for every increase in mm Hg of the IOP over the mean study IOP; the risk was increased by 32% for each 0.1 increment in vertical cup–disc ratio.

Results from the OHTS suggest that older age, higher IOP, thinner corneas, a larger baseline cup–disc ratio, and higher pattern standard deviation on standard automated perimetry are important risk factors for the development of POAG. The increased risk of glaucoma progression attributed to thinner corneas in this study, however, was not fully explained by the estimated artifactual error in measured IOP. Thinner corneas may therefore be a biomarker for glaucoma susceptibility based on factors other than IOP. The increased risk of glaucoma progression in black participants (in univariate but not multivariate analyses) may be attributed to thinner corneas and greater cup–disc ratios. Interestingly, a family history of glaucoma was not identified as a significant risk factor in the OHTS, possibly because of inadequate assessment from self-reporting. Clinicians should consider family history when evaluating a patient’s risk of glaucoma. Other potential risk factors, such as myopia, diabetes mellitus, migraine, and high or low blood pressure, were not confirmed in the OHTS as significant risk factors for glaucomatous progression.

Initial reports from the OHTS clearly demonstrate that lowering IOP in individuals with ocular hypertension reduces the risk of progression to glaucoma. It is important to recognize, however, that the incremental structural or functional change that constituted a progression endpoint in the OHTS would likely not manifest as symptomatic vision loss. Therefore, the question remains whether delaying treatment is associated with poorer outcomes than early initiation of IOP-lowering therapy. The results from the OHTS suggest that clinicians may safely consider delaying the treatment of ocular hypertension, particularly among patients with a lower risk of conversion to glaucoma (see Clinical Trial 7-2). This suggestion is supported by the longer-term follow-up of the OHTS participants in which it was found that delayed initiation of treatment still resulted in a decrease in the rate of developing glaucoma, just as it did earlier in the course. After 13 years, 71% of the original participants were still in the study; 22% of those originally assigned to observation (and offered treatment after the first phase of the study) developed glaucoma, compared to 16% in the group assigned to medication.

The decision of whether to treat a patient with ocular hypertension may be based on a combination of the results from the OHTS, findings from the clinical examination, and discussions with the patient. The clinician and patient should consider whether the risk of developing glaucoma outweighs the inconvenience, cost, and potential side effects of therapy for the patient. Additional factors to consider include the patient’s age and likely life span; for patients with no damage and a relatively short life expectancy, it may be reasonable to observe rather than treat. Data from the OHTS and the European Glaucoma Prevention Study were combined to create a risk calculation model (https://ohts.wustl.edu/risk) to help clinicians predict the 5-year risk of conversion from ocular hypertension to glaucoma, based on risk factors in the 2 studies (ie, older age, higher IOP, thinner corneas, a larger baseline cup–disc ratio, higher pattern standard deviation on standard automated perimetry).

• Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002; 120(6):714–720; discussion 829–830.

• Kass MA, Gordon MO, Gao F, et al. Delaying treatment of ocular hypertension: The Ocular Hypertension Treatment Study. Arch Ophthalmol. 2010;128(3):276–287.

• Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701–713; discussion 829–830.