We thank Drs Quaranta and Floriani for their interest in our publication. The Low-pressure Glaucoma Treatment Study (LoGTS) is a randomized trial of the effect of brimonidine versus timolol on preserving visual function in patients with low-pressure glaucoma. The LoGTS is an important trial for various reasons. It is the first randomized clinical trial to demonstrate the possibility of a pressure-independent treatment effect in glaucoma. It is also the first prospective randomized clinical trial to compare the impact of topical therapy on visual function by using a trend analysis approach to detect progression. By enrolling patients with very low baseline intraocular pressure (IOP), it demonstrates the power of having an enriched study population that minimizes the impact of IOP on disease progression and may serve as a model for future neuroprotection trials. Last, direct comparisons between drugs may be necessary in the future to demonstrate the cost effectiveness of new therapies.
In contrast to the suggestions by Drs Quaranta and Floriani, our article specifically recommends against changing current clinical care paradigms pending additional basic science and clinical research to confirm the results demonstrated in the LoGTS. Similarly, we suggest the same conclusion be applied to the recommendation by Drs Quaranta and Floriani, who suggest “avoidance” of both timolol and brimonidine in normal-tension glaucoma patients based on reduction of ocular perfusion pressure identified in 27 patients.
Although baseline diurnal IOP measurements were performed in the LoGTS after medication washout, 24-hour IOP measurements were not performed. We agree it would be of interest to study nocturnal IOP further in this cohort. We disagree that progressive visual field loss should be considered a defining feature of low-pressure glaucoma, because many studies have demonstrated that a substantial proportion of low-pressure glaucoma patients do not progress.
Visual fields in LoGTS were analyzed using both trend and event analyses. Visual field progression required confirmation at the next 2 examinations, with the earliest possible progression detected at month 16 (8 months to calculate pointwise linear regression for the negative slopes and months 12 and 16 for confirmation). There are many ways to analyze the data further, including ocular perfusion pressure (blood pressure and pulse were measured at 4-month visits). The question of dropouts during the course of the study was stressed in the publication; these were considerably higher in the brimonidine-treated eyes, as was expected from the inception of the study. This is consistent with clinical experience using brimonidine tartrate 0.2%. Patients were stratified in blocks of 7 (4 to brimonidine, 3 to timolol) at the time randomization.
In summary, our results demonstrate that brimonidine preserves visual function better than timolol when used as monotherapy in eyes in which ocular allergy did not develop. The mechanism may be related to a beneficial effect associated with brimonidine, a detrimental effect associated with timolol, or both. As described in the article, 24-hour IOP control, ocular perfusion pressure, compliance, and other unknown and unmeasured variables may have contributed to the study outcome.
The LoGTS trial emphasizes the need for further research in the field of neuroprotection.