29.3  What Is the Natural History

of Untreated vs. Treated

Ocular Hypertension?

29.3.1  Ocular Hypertension Treatment

Study

Until recently, no consensus existed as to whether eyes with elevated IOPs should be medically treated or not. Multiple studies examining this question were either inconclusive or yielded contradictory results. The OHTS was designed to definitively answer this question. Begun in 1994, the initial results of this large-scale, multi-center clinical trial were published in 2002 [7]. The study population included 1,636 people 40–80 years of age who had elevated eye pressure (24–32 mmHg) but showed no signs of glaucoma by either visual field or optic nerve head exam. Half of the patients were assigned to daily topical glaucoma drops and the other half was assigned to observation. All enrollees had sequential visual field examination and optic nerve head photography. IOP lowering was 22.4% in the treatment arm and stable in the control arm (−4.0%).

Baseline factors that were predictive of developing glaucomatous optic neuropathy included older age, higher IOP, lower central corneal thickness (CCT), larger vertical cup-to-disc ratio and higher pattern standard deviation. Overall, 4.4% of the treatment group advanced to POAG while 9.5% of the observation group progressed by visual field and/or optic nerve changes. This translates to a number-needed-to-be- treated of 16 patients to prevent one case of glaucoma in 5 years.

29.3.2  The European Glaucoma

Prevention Study

As with OHTS, the EGPS was a randomized, multi-­ center, controlled trial designed to evaluate the ­effi­cacy of IOP reduction in preventing or delaying the devel­ opment of OAG in ocular hypertension subjects [8, 9].

The entry criteria for patient enrollment were sub­ stantially similar to that for OHTS and 1,081 patients were enrolled. However, unlike in OHTS, subjects ran­ domized to treatment received dorzolamide only. Dorzolamide reduced IOP in treated patients by a mean of 15% after 6 months and 22% after 5 years. The number­ -needed-to-treat (NNT) with dorzolamide to prevent one case of glaucoma was 143 patients. Interestingly, IOP also declined in the observation group by a mean of 9 and 19% after 6 months and 5 years respectively. As might be expected with similar IOP reductions between groups, the cumulative probability of developing an end point after 5 years of follow-up was not significantly­ different­ statistically between the two randomized groups. However, the EGPS did find that higher mean IOP at baseline in both treated and untreated subjects was significantly­ associated with the development of glaucoma. Thus, as with OHTS, the significance of IOP in the pathogenesis of glaucoma was affirmed. Perhaps the most important contribution of EGPS was that the predictive­ factors for glaucoma development found in OHTS were validated in an independent study population.

Summary for the Clinician

››The OHTS and EGPS clearly show that high IOP is a risk factor for developing glaucomatous opticneuropathyandthatloweringIOPdecreases the conversion rate from ocular hypertension to manifest glaucomatous optic neuropathy.

››EGPS limited treatment of patients to topical dorzolamide, thus not mimicking the initial treatment choice of prostaglandin analogs used in most practices today. It is unclear how this influenced findings in this study.

››The number-needed-to-treat (NNT) in OHTS is 16 ocular hypertensives to prevent one case of conversion to glaucoma using a 20% IOP reduction.

››The NNT in EGPS is 143 ocular hypertensives to prevent one case of conversion to glaucoma using dorzolamide alone.