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Editors Selection IGR 13-1

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Comment by Ivan Goldberg on:

27800 A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study, Krupin T; Liebmann JM; Greenfield DS et al., American Journal of Ophthalmology, 2011; 151: 671-681

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This paper by Krupin and colleagues was concerned with the evaluation of visual field progression for two groups of patients with low pressure glaucoma who were treated with Brimonidine and timolol for a period of approximately four years, with evaluations at fourmonth intervals. There were a greater number of patients randomized to brimonidine (99) compared to timolol (79) because of the anticipated greater dropout rate for brimonidine. The authors report that there was a lower rate of visual field progression in the group receiving brimonidine in comparison to the Timolol group, despite the fact that IOP lowering was essentially similar between the two groups. In general, the study was performed in a careful, masked fashion, the analysis was performed by several different criteria for determining visual field progression, an assessment of visual field improvement was performed, and careful consideration of other ocular and systemic factors was also determined. The authors speculate on possible IOP related and non-IOP related reasons for the difference in visual field progression between the two groups.

This investigation provides important information for practitioners treating and monitoring low-pressure glaucoma patients, and raises some interesting questions concerning the basic pathophysiologic mechanisms that are influenced by the two treatment medications. However, there are some aspects of the study that deserve further assessment: (1) One of the criteria for enrollment was the confirmation of visual field loss by confirming optic disc damage in an appropriate location. Most studies have demonstrated 50% or less agreement between structure and function in glaucoma. Does this bias the sample of patients included in this study? (2) Approximately 25% of the patients provided one eye for evaluation in the study, while 75% included both eyes. The data from both eyes are correlated to an extent, but there are methods to adjust for this correlation such as Generalized Estimating Equations (GEE). It would be useful to re-analyze the results using these methods. (3) Generalized, widespread or diffuse loss was not considered in this study by using the Pattern Deviation probability maps. However, recent evidence by Artes and Colleagues (Arch Ophthalmol 2010, 128: 1528-1532) indicate that the Total Deviation probability map provides better cross sectional and longitudinal information for visual field progression, and that diffuse visual field deficits are a predominant feature of glaucomatous visual field loss. It would be useful to reanalyze the data according to Total Deviation probabilities, given that the time period of evaluation is rather short and the development or progression of cataract is unlikely. (4) There is typically only about 50-60% agreement among different methods of determining glaucomatous visual field progression, and the results for brimonidine and timolol show this for the progressing group. This is also the case for timolol in the stable visual field group, but brimonidine shows approximately 90% agreement among the progression analyses for the stable group. Why? An evaluation of IOP diurnal variation and other non- IOP factors may be revealing in this regard.

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