**Background:** Elevated intraocular pressure (IOP) is the only treatable risk factor for glaucoma, but it does not fully explain disease pathogenesis. Previous research by the authors identified high pulse rate (PR) as a risk factor for reduced ocular blood flow (BF) and subsequent glaucomatous neural loss. β-Blocker eye drops, commonly used to lower IOP by reducing aqueous humor production, also reduce PR via systemic absorption and β1-receptor blockade. However, their effects on PR and ocular BF in real-world glaucoma populations, especially over long-term follow-up, were not well characterized. This study aimed to determine whether β-blocker eye drops reduce PR in a real-world glaucoma cohort, identify clinical factors associated with greater PR reduction, and assess whether a subgroup of patients experiences improvements in ocular BF and slowed glaucoma progression.
**Methods:** This retrospective study included 236 eyes of 138 glaucoma patients (mean age 59.8 ± 14.7 years; 70 male, 68 female) from Tohoku University Hospital who received a β-blocker eye drop add-on between April 2009 and February 2022. Inclusion required at least one PR measurement before and after the add-on. Data collected included longitudinal PR, IOP, choroidal BF (via laser speckle flowgraphy-measured mean blur rate [MBR]), and oxidative stress (diacron-reactive oxygen metabolites [d-ROMs]). Linear mixed-effects models were used to assess the effect of the β-blocker add-on on PR, IOP, and BP, adjusting for age, gender, time, cataract surgery, and glaucoma surgery. Interaction terms between the add-on and clinical factors (age, gender, diabetes, CCT, d-ROM, baseline PR) were tested to identify predictors of PR reduction. K-means clustering (based on age, gender, diabetes, baseline PR, PR change, baseline choroidal MBR, choroidal MBR change, CCT, d-ROM, MD slope before add-on, and MD slope change) identified patient subgroups. In each cluster, the effect of the add-on on choroidal MBR and MD slope was analyzed using linear mixed-effects models.
**Key Results:** The β-blocker add-on significantly reduced PR by −7.61 bpm (P < 0.001) and IOP by −0.90 mmHg (P < 0.001). Non-β-blocker eye drops did not significantly reduce PR. Factors associated with greater PR reduction included female gender (P = 0.028), higher baseline PR (P < 0.001), lower central corneal thickness (CCT; P = 0.024), and higher d-ROM level (P = 0.001). K-means clustering identified two clusters: Cluster 1 (77 eyes, 44 patients) had a higher proportion of females (93.2%), higher baseline PR (86.1 ± 13.7 bpm), greater PR reduction (−12.4 ± 10.0%), lower CCT (500.2 ± 31.2 μm), higher d-ROM (391.8 ± 60.0 U. Carr), and lower baseline choroidal MBR (6.4 ± 1.9 AU) compared to Cluster 2. In Cluster 1, the β-blocker add-on increased choroidal MBR by +3.42% (P = 0.042) and improved MD slope by +0.64 dB/year (P = 0.005). In Cluster 2, no significant changes in choroidal MBR (−3.09%, P = 0.081) or MD slope (+0.10 dB/year, P = 0.687) were observed.
**Clinical Implications:** This study identifies a specific glaucoma subgroup—characterized by female gender, higher baseline PR, thinner corneas, and elevated oxidative stress—in which β-blocker eye drops not only reduce PR but also improve choroidal blood flow and slow visual field progression. These benefits appear independent of IOP reduction, as IOP reduction was smaller in this subgroup. The findings suggest that β-blocker eye drops may have a protective role beyond IOP lowering in selected patients, potentially by normalizing PR and enhancing ocular perfusion. This challenges the traditional view of β-blocker-induced bradycardia as merely a side effect and opens new discussions about personalized glaucoma therapy. However, due to the retrospective design and potential selection bias (e.g., exclusion of elderly or cardiac patients), prospective multicenter studies are needed to confirm these results and assess generalizability to other populations.