Understanding Individual Intraocular Pressure Response to Treatment with Latanoprost and Timolol

<b><i>Purpose:</i></b> To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. <b><i>Methods:</i></b> In this multicenter, randomized, crossover study (NCT01677507), both eyes of 106 healthy subjects (212 eyes) were treated with latanoprost or timolol for 7 days, with a 6-week washout between treatments. Ocular biometrics, tonometry, and aqueous humor dynamics (AHD) were assessed at baseline and day 8 of each treatment. Subjects were divided into responders and nonresponders using cutoffs of >15% or >10% IOP reduction. Treatment effects and correlations were analyzed with paired t-tests. <b><i>Results:</i></b> More subjects responded to latanoprost (54%) than timolol (27%) at >15% cutoff (<i>p</i> < 0.01). Responders had higher mean baseline IOP than nonresponders for both drugs at both cutoffs (<i>p</i> < 0.01). Among timolol nonresponders (<i>n</i> = 56), 39% responded to latanoprost in both eyes, 20% in one eye, and 41% in neither. Among latanoprost nonresponders (<i>n</i> = 31), 13% responded to timolol in both eyes, 13% in one eye, and 74% in neither. Latanoprost increased uveoscleral outflow, while timolol reduced aqueous flow and outflow facility. Low baseline uveoscleral outflow was associated with latanoprost response. <b><i>Conclusions:</i></b> Higher baseline IOP predicted better responses to both drugs. Higher baseline uveoscleral outflow predicted nonresponse to latanoprost. No AHD differences were linked to the timolol response. Timolol nonresponders were often responsive to latanoprost, but not vice versa.