This article shares Baltimore surgeon Harry Quigley's thoughts on how to interpret the AGIS results in terms of clinical practice.
GENERALIZING RESULTS
Dr. Quigley emphasizes that, in accordance with the study's design, the IOP of AGIS subjects was substantially higher than that of glaucoma subjects randomly selected from the population. For that reason, he urges caution in generalizing the AGIS results to all patients.
“It could be that glaucoma patients with field damage whose average eye pressure under therapy is 25 mm Hg respond differently from patients whose baseline eye pressure was 15 mm Hg,” he states. “While I believe that the AGIS result is highly documented and very important, any time you look at the results of a clinical trial, you have to ask, ‘who were the people recruited for the study, and how [much can we generalize] … its conclusions?'”
PRACTICAL PEARLS
When asked to identify the important clinical implications of AGIS, Dr. Quigley selected the following. First, the study confirms that ALT can benefit patients long-term with minimal risk, and, second, ALT works approximately as well in white as in black patients. Third, without the use of antifibrotic agents, trabeculectomy was somewhat more effective in white than black patients. Fourth, a lot of the study's patients continued using medical therapy 3 to 5 years after the initial intervention. Fifth, cataract formation is a serious complication of trabeculectomy and, Dr. Quigley notes, possibly also of medical therapy, according to the Ocular Hypertension Treatment Study.7,8 Sixth, removing a cataract does not greatly improve the visual field test, and, finally, the general decline in function of a patient treated for glaucoma is fairly modest. Dr. Quigley elaborates on the last point.
“The outcome of glaucoma under treatment is such that, among all those with glaucoma, proportionately few go blind in their lifetime from it,” he explains. “That's a conclusion based on, not only AGIS data, but lots of other data, although it's quite controversial among glaucoma specialists.”
Other glaucoma subspecialists, he acknowledges, would strongly disagree that most glaucoma patients do well. He observes, however, that the AGIS subgroup with the highest IOP and worst rate of progressive field change experienced an average loss of 2 AGIS field units in 8 years (scale of 0=no defect to 20=end stage; the median baseline AGIS score was 8).
PROBLEMATIC INTERPRETATION
“The main interpretation by the AGIS investigators of their result has been shortened to a phrase: ‘surgery for whites and laser for blacks,'” comments Dr. Quigley. “I would conclude from the study data that this is not a correct statement. Based on the data shown to me, AGIS overall found no difference between doing laser or surgery in the total study population before you stratify; in other words, it didn't matter, after medicines failed, if you did laser first or surgery first.”
He acknowledges that stratifying subjects by race did demonstrate that ALT was slightly more successful in black patients and trabeculectomy somewhat more effective in white patients. Dr. Quigley asserts, however, that this stratification does not account for the facts that the black study patients had more severe glaucoma and were using slightly more medicine. He states that, when severity was accounted for, the differences by race were very small. His interpretation of the data is that ALT works equally well in both subject groups. Dr. Quigley therefore believes that the average patient with glaucoma should be given the option of undergoing ALT with a statement resembling the following: “[With] this laser treatment, [there is] a little better than a 50/50 chance that you'll stay in your target [IOP] zone for the next 5 years while continuing medicine, and there is very little risk—certainly no detectable risk of increasing cataract and no risk of infection in the eye and very little risk of any central visual loss.”
Dr. Quigley expresses concern that accepting and promulgating the practice pattern of “surgery for whites and laser for blacks” may lead white patients to reject ALT as a possible treatment option, because they will believe it ineffective for white people in general. Although the best 5-year result in white AGIS patients in terms of the visual field test was surgery, he emphasizes that this option also entails a risk of cataract formation, bleeding, infection, and potentially serious complications, all of which the patient must accept.
PRACTICE EVOLUTION
The main issue with clinical trials, which can last 8 years, is that clinical practice continues to evolve during the study period.
“We're now faced with what amounts to a new clinical situation, and we have to extrapolate what might have been true,” Dr. Quigley says. “Instead of speaking from the data themselves, we are now trying to guess.”
When interpreting the AGIS results, he notes, a potentially confounding factor is the fact that antifibrotic agents were not used in the first trabeculectomy received by most study subjects.
“The success rate for black persons from surgery might be more equal to whites' if the beneficial effect of the mitomycin C, for example, is the bigger factor,” he explains. “It may not be if complications from the use of mitomycin C are the greater factor. There's certainly evidence that mitomycin C may make cataracts even more likely to happen, and certainly very low eye pressures and the side effects that result from hypotony might be more likely with mitomycin C.”
Harry A. Quigley, MD, is Director of Glaucoma Services at The Wilmer Eye Institute, Johns Hopkins University, Baltimore. Dr. Quigley may be reached at (410) 955-2777; hquigley@jhmi.edu.
1. The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients. Ophthalmology. 1998;105:1137-1145.
2. The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes within race. Seven-year results. Ophthalmology. 1998;105:1146-1164.
3. The AGIS Investigators. The Advanced Glaucoma Intervention Study, 6: Effect of cataract on visual field and visual acuity. Arch Ophthalmol. 2000;118:1639-1652.
4. The 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.
5. The Advanced Glaucoma Intervention Study (AGIS): 8. Risk of cataract formation after trabeculectomy. Arch Ophthalmol. 2001;119:1771-1779.
6. 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.
7. 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.
8. 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;120:714-720.
