Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients

<b>Background/Objectives</b>: To analyze the genotype that predicts the phenotypic characteristics of a cohort of patients with glaucoma and ocular hypertension (OHT) and explore their influence on the response to ocular hypotensive treatment. <b>Methods</b>: This was a prospective study that included 193 eyes of 109 patients with glaucoma or OHT under monotherapy with beta-blockers, prostaglandin, or prostamide analogues (BBs, PGAs, PDs). Eight single-nucleotide polymorphisms were genotyped using real-time PCR assays: prostaglandin-F2α receptor (<i>PTGFR</i>) (rs3766355, rs3753380); beta-2-adrenergic receptor (<i>ADRB2</i>) (rs1042714); and cytochrome P450 2D6 (<i>CYP2D6</i>) (<i>*2</i> rs16947; <i>*35</i> rs769258; <i>*4</i> rs3892097; <i>*9</i> rs5030656, and <i>*41</i> rs28371725). The main variables studied were baseline (bIOP), treated (tIOP), and rate of variation in intraocular pressure (vIOP), and mean deviation of the visual field (MD). The metabolizer phenotype and the <i>CYP2D6</i> copy number variation were also evaluated. <b>Results</b>: In total, 112 eyes were treated with PGAs (58.0%), 59 with BBs (30.6%), and 22 with PDs (11.4%). For <i>PTGFR</i> (rs3753380), statistically significant differences were observed in vIOP in the PGA group (<i>p</i> = 0.032). Differences were also observed for <i>ADRB2</i> (rs1042714) in MD (<i>p</i> < 0.001) and vIOP (<i>p</i> = 0.017). For <i>CYP2D6</i>, ultrarapid metabolizers exhibited higher tIOP (<i>p</i> = 0.010) and lower vIOP (<i>p</i> = 0.046) compared to the intermediate and poor metabolizers of the BB group. Additionally, systemic treatment metabolized by <i>CYP2D6</i> showed a significant influence on vIOP (<i>p</i> = 0.019) in this group. <b>Conclusions</b>: These preliminary findings suggest the future potential of pharmacogenetic-based treatments in glaucoma to achieve personalized treatment for each patient, and thus optimal clinical management.