Methodologic Aspects of Glaucoma Phamacogenomic Studies

McCarty et al¹ studied the association between intraocular pressure (IOP) response to topical β-blockers and genotype. Several factors are associated with IOP response such as concurrent use of IOP-lowering medication,¹ baseline IOP,^{2 - 4} and cup-disc ratio.⁴ Patients' races were not provided. Whether treatment was monocular might matter because of association with glaucoma type (eg, angle recession) and because binocular treatment provides 2 opportunities for a specified pressure drop. The criteria of McCarty et al might have included patients with ocular hypertension, primary open-angle glaucoma, or glaucoma due to chronic angle closure, pseudoexfoliation, angle recession, pigmentary change, steroid response, uveitis, neovascularization, or other causes. Genotyping will be most helpful when it provides information not already known. Race, concurrent IOP-lowering medication regimen, baseline IOP, type of glaucoma, number of eyes treated, and cup-disc ratio should be controlled for in the multivariable prediction of IOP response (Table 4 of McCarty et al¹ ).

The stated IOP response median of −23.3 mm Hg and range from −70.8 mm Hg to +25.0 mm Hg seem quite high. The conversion of binocular IOP data at several baseline and follow-up visits to a binary variable based on maximal IOP drop reduces the value of the information. The best routinely available IOP response measurement is mean IOP during treatment minus the mean IOP without treatment.^{2 - 3} Preservation of IOP response as a continuous (or rank) variable can increase the sensitivity to detect differences among genotypes. Multivariable linear regression can be used to predict the IOP response.^{2 - 3} Nonnormality can be approached by modifying outliers, data transformation, or using a nonparametric equivalent.

Correspondence: Dr Leffler, Department of Ophthalmology, Virginia Commonwealth University, Medical College of Virginia Campus, 403 N 11th St, Box 980209, Richmond, VA 23298-0209 (cleffler@pol.net).

Financial Disclosure: None reported.