The Low-Pressure Glaucoma Study by Krupin and associates reported a significantly lower rate of visual field progression in the brimonidine group (9%) compared to the timolol group (39%). They discuss that this could be attributable to an intraocular pressure (IOP)–independent protective effect of brimonidine or a relative harmful effect of timolol. This beneficial effect of brimonidine could have a major impact on how we treat patients with low-pressure glaucoma. We would like to highlight certain aspects of this study that might limit the extrapolation of the results.
Significantly more subjects assigned to the brimonidine group (54/99, 54.5%) dropped out of the study compared to the timolol group (23/79, 29.1%). A majority of discontinued patients dropped out prior to the month-16 examination (41/54, 75.9% in brimonidine group and 10/23, 43.4% in timolol group), which was the earliest study visit to determine the primary outcome of the study. Therefore, intent-to-treat analysis is not applicable to these data. Unequal numbers of subjects dropping out from the study groups may have skewed the results in favor of brimonidine. The authors present data that patients lost to follow-up prior to year-1 examination were not significantly different from those who had follow-up of ≥1 year. As the involved numbers were small, absence of a statistically significant difference need not necessarily mean that these groups were similar. Biased results as unexpected as placebo being equal to dorzolamide have resulted from major loss to follow-up in a well-conducted randomized clinical trial. Considering patients lost to follow-up as progressed (worst-case scenario), the number of patients progressing in the brimonidine group (50/99, 50.5%) is similar to that in the timolol group (41/79, 51.9%, P = .97, χ 2 test).
The number of subjects reaching study end without visual field progression was comparable between the groups by all outcome measures (pointwise linear regression analysis P = .61, glaucoma change probability maps P = .41, and 3-omitting method for pointwise linear regression P = .59, χ 2 test). The proportion should have favored the brimonidine group if indeed brimonidine were superior to timolol.
The Collaborative Normal-Tension Glaucoma Treatment Study (CNTGS) specifically avoided timolol because of its vasoactive action. The 3-year visual field progression rate in the timolol-treated group in the current study is comparable to that in the IOP-lowered arm of the CNTGS, as the authors themselves have pointed out. This observation does not support the contention that timolol is harmful in low-pressure glaucoma. The results of this report from the Low-pressure Glaucoma Treatment Study may need validation before they could be extrapolated to larger clinical practice.