Background/Objectives: 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. Methods: 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 (PTGFR) (rs3766355, rs3753380); beta-2-adrenergic receptor (ADRB2) (rs1042714); and cytochrome P450 2D6 (CYP2D6) (*2 rs16947; *35 rs769258; *4 rs3892097; *9 rs5030656, and *41 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 CYP2D6 copy number variation were also evaluated. Results: In total, 112 eyes were treated with PGAs (58.0%), 59 with BBs (30.6%), and 22 with PDs (11.4%). For PTGFR (rs3753380), statistically significant differences were observed in vIOP in the PGA group (p = 0.032). Differences were also observed for ADRB2 (rs1042714) in MD (p < 0.001) and vIOP (p = 0.017). For CYP2D6, ultrarapid metabolizers exhibited higher tIOP (p = 0.010) and lower vIOP (p = 0.046) compared to the intermediate and poor metabolizers of the BB group. Additionally, systemic treatment metabolized by CYP2D6 showed a significant influence on vIOP (p = 0.019) in this group. Conclusions: 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.

Glaucoma is a chronic, degenerative eye disease for which personalized diagnostic and therapeutic biomarkers are still lacking. Precision medicine offers a promising strategy to improve glaucoma management, and pharmacogenomics may play a key role in optimizing treatment response, minimizing side effects, and enhancing adherence. Advances in genetics have introduced potential tools such as polygenic risk scores (PRS) for adult-onset glaucoma and CRISPR/Cas9 for early-onset monogenic forms. Although still in its early stages, pharmacogenetic research in glaucoma has identified several genetic variants that may influence drug efficacy and security. Notably, single nucleotide polymorphisms in genes such as PTGFR, ADRB2 and CYP2D6 have been associated with varied responses to beta-blockers and prostaglandin analogues. Other candidate genes include ABCB1, SLCO2A1, AFAP1, and ADRB1, though findings remain preliminary. Despite the appeal of genetically guided therapy, broader implementation in clinical practice requires larger, multicenter validation studies, functional analysis of variants, and consensus on actionable biomarkers. Until then, early diagnosis, adherence, and timely treatment remain the pillars of glaucoma care. This narrative review provides an updated overview of the current evidence, knowledge gaps, and future directions in the pharmacogenomics of glaucoma.

Purpose: To report a rare case of bilateral conjunctival and epibulbar extranodal Rosai-Dorfman disease (RDD) without lymph node involvement, potentially associated with long-term use of benzalkonium chloride (BAK)-containing glaucoma medications. Case Presentation: A 68-year-old male with a 10-year history of primary open-angle glaucoma, managed with multiple topical hypotensive agents, developed bilateral conjunctival and epibulbar nodules following chronic recurrent episodes of conjunctival inflammation over those 10 years. Histopathological examination and immunohistochemical staining confirmed the diagnosis of RDD, characterized by histiocytic proliferation with prominent emperipolesis. The patient underwent surgical excision of the lesions with homoconjunctival grafting. Postoperatively, his glaucoma regimen was modified to a preservative-free (BAK-free) topical therapy, and selective laser trabeculoplasty was performed to reduce the need for additional topical therapy. Comprehensive systemic evaluation revealed no lymphadenopathy or other extranodal organ involvement. At one-year follow-up, there was no evidence of recurrence, conjunctival inflammation had markedly subsided, and the glaucoma remained stable. Conclusions: This case highlights a potential association between chronic conjunctival inflammation induced by BAK-containing glaucoma medications and the de novo emergence of epibulbar RDD. Although RDD remains a rare and poorly understood histiocytic disorder, our findings suggest that sustained ocular surface inflammation may act as a trigger in its pathogenesis. To our knowledge, this is the first reported case of ocular RDD potentially linked to long-term exposure to topical hypotensive therapy. Further studies are warranted to investigate the role of chronic inflammatory stimuli in the development of extranodal RDD, particularly within ocular tissues.