TY - JOUR
AU - Lichter, Paul R.
AB - Abstract Objective To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. Design Randomized clinical trial. Participants Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, −4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. Interventions Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. Main Outcome Measures Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as thesame 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. Results After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P = .007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P = .002). Conclusions The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss. Commentary Open-angle glaucoma is a common clinical problem, affecting an estimated 1 million persons in the United States and perhaps another million who do not know they have the disease. The condition, a major worldwide public health problem1 may be associated with elevated intraocular pressure (IOP), but also commonly presents with normal IOP. Reduction of IOP is the mainstay of treatment for glaucoma, even though irrefutable clinical trial data to prove its effectiveness have not been available. Some health care policy experts2 had expressed skepticism about the value of treating glaucoma. However, the Early Manifest Glaucoma Trial (EMGT)3 published in the October 2002 issue of the Archives of Ophthalmology, provides convincing evidence that reduction of IOP is effective in reducing visual field loss. The EMGT was conducted in Sweden under the cosponsorship of the National Eye Institute and the Swedish Research Council. Patients with newly diagnosed open-angle glaucoma were randomly assigned to a treatment group or to an untreated control group. Patients in the treatment group received betaxolol eyedrops and argon laser trabeculoplasty– whereby the trabecular meshwork (the site along the route of aqueous egress from the eye) is treated with 100 individual laser spots to improve aqueous outflow and thereby lower the IOP. Patients assigned to the control group received no initial therapy, but were monitored carefully, and at the earliest progression of disease, were immediately offered treatment. Thus, no untreated patients were allowed to experience a significant amount of visual field loss.4 After a median follow-up of 6 years, IOP was reduced by a mean of 5.1 mm Hg (approximately 25%) in the treated group; disease progression was significantly less frequent in the treatment group than in the control group (45% vs 62%) and occurred significantly later. While these main outcomes have major clinical importance, the EMGT also provides several other important lessons. First, every 1-mm Hg reduction in IOP in the EMGT was associated with an approximately 9% reduction in the risk of visual field loss. This finding emphasizes the effectiveness of the extent of IOP reduction in preventing or reducing glaucomatous damage. Second, ocular medications used to reduce IOP, such as betaxolol, have potential adverse effects, along with additional cost and nuisance. In the EMGT, 22 deaths occurred during the study period, including 15 deaths among treated patients and 7 deaths among controls, with most deaths due to cardiovascular disease. Although this difference between groups was not statistically significant (P = .08), the finding provides reason to emphasize that topical ocular medications are systemic drugs, by virtue of their local absorption as well as their passage through the lacrimal system. Third, while observational studies have shown that increased IOP is a risk factor for visual field loss and that glaucomatous damage can be expected to progress over 6 years of follow-up,5-7 the results of the EMGT are most valuable when considered in the context of other glaucoma clinical trials. While the IOP among the treated patients in EMGT decreased from baseline by about 25%, this reduction was not sufficient to prevent progression of visual field loss in all patients. While the study was not designed to eliminate visual field loss in treated patients, the question remains as to whether even further IOP reduction could have prevented visual field loss in more patients. In the Ocular Hypertensive Treatment Study,8 patients with elevated IOP but no glaucomatous damage who were randomized to IOP-lowering treatment had a mean IOP reduction of 22%. Treatment reduced the development of glaucomatous damage to 4.4% compared with 9.5% in the untreated group after 5 years of follow-up. In the Collaborative Initial Glaucoma Treatment Study, IOP was reduced by a mean of 45% in all patients, enough to greatly reduce visual field loss over a 5-year follow-up period.9 The Advanced Glaucoma Intervention Study demonstrated that patients whose IOP never reached as high as 18 mm Hg during a minimum 7-year follow-up experienced minimal visual field loss.10 Thus, there may be an IOP below which visual field loss can be prevented in most cases. Fourth, as with clinical trials in other chronic diseases, such as systemic hypertension and diabetes mellitus, it is tempting to use the results of the EMGT to generalize the tested treatment to all patients. Clinical trials generally follow rigid protocols that do not mirror everyday life or everyday medical practice. Randomization does not allow for physician judgment for each patient. The trial population may not reflect the general patient population that may be subjected to the trial's results in terms of treating the disease in question. For example, patients in the EMGT were essentially all white whereas glaucoma is a disease that is more common and has a more severe course in blacks.11 Finally, in contrast to what most practicing physicians were taught in medical school about glaucoma, approximately half of the patients in the EMGT with early open-angle glaucoma had mean baseline IOP of less than 21 mm Hg, but had characteristic glaucomatous visual field loss. This points to the recognition that glaucoma is really an optic neuropathy influenced by IOP, but is not dependent on a particular IOP level. Therefore, glaucoma screening based on elevated IOP alone may miss as many as half the patients with glaucoma. As important as IOP is in this disease, many cases are detected only by recognizing characteristic glaucomatous optic disc cupping during funduscopic examination. The EMGT is a well-conceived study that has provided useful and irrefutable evidence that lowering IOP reduces the risk of progressive visual field loss. Additional results from future clinical trials and observational studies, added to the findings of the EMGT, will result in better understanding of when and how much to lower the IOP, as well as what the impact of treatment and the disease itself will have on a patient's quality of life.12 Previous Publication: The abstract was published in the October 2002 issue of Archives of Ophthalmology (2002;120:1268). References 1. Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol.1996;80:389-393.Google Scholar 2. Eddy DM, Billings J. The quality of medical evidence: implications for quality of care. Health Aff (Millwood).1988;7:19-32.Google Scholar 3. Heijl A, Leske MC, Bengtsson B. et al. Reduction of intraocular pressure and glaucoma progression results from the Early Manifest Glaucoma Trial. Arch Ophthalmol.2002;120:1268-1279.Google Scholar 4. Lichter PR. Expectations from clinical trials: results of the Early Manifest Glaucoma Trial (EMGT). Arch Ophthalmol.2002;120:1371-1372.Google Scholar 5. Watson PG, Grierson I. The place of trabeculectomy in the treatment of glaucoma. Ophthalmology.1981;88:175-196.Google Scholar 6. Jay JL, Murray AB. Early trabeculectomy versus conventional management in primary open-angle glaucoma. Br J Ophthalmol.1988;72:881-889.Google Scholar 7. Migdal C, Gregory W, Hitchings R. Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology.1994;101:1651-1657.Google Scholar 8. 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;120:701-713.Google Scholar 9. Lichter PR, Musch DC, Gillespie BW. et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology.2001;108:1943-1953.Google Scholar 10. AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. the relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol.2000;130:429-440.Google Scholar 11. AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 9. comparison of glaucoma outcomes in black and white patients within treatment groups. Am J Ophthalmol.2001;132:311-320.Google Scholar 12. Janz NK, Wren PA, Lichter PR. et al. The Collaborative Initial Glaucoma Treatment Study: interim quality of life findings after initial medical or surgical treatment of glaucoma. Ophthalmology.2001;108:1954-1965.Google Scholar
TI - Impact of Intraocular Pressure Reduction on Glaucoma Progression
JO - JAMA
DO - 10.1001/jama.288.20.2607
DA - 2002-11-27
UR - https://www.deepdyve.com/lp/american-medical-association/impact-of-intraocular-pressure-reduction-on-glaucoma-progression-0XUCbPWSfk
SP - 2607
EP - 2608
VL - 288
IS - 20
DP - DeepDyve
ER -