Identification of a Novel Subtype of Ocular Hypertensive Eyes with the Lowest Risk of Progression Under Treatment

Introduction: Our aim in this work is to identify a subtype of ocular hypertensive eyes that benefited the most from topical hypertensive medication. Methods: We included 1636 patients (817 patients in the active group and 819 in the observation group) who participated in the Ocular Hypertension Treatment Study (OHTS). We developed principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and unsupervised density-based clustering, then applied to the baseline visual fields (VFs) to identify different clusters of eyes. For each cluster, the rate of mean deviation (MD) worsening was calculated based on 7 years of follow-up. To determine which cluster (subtype) of eyes responded better to the ocular hypertensive medications, MD worsening was compared between the active and observation groups within each cluster of eyes separately. Results: We identified 13 clusters based on visual field (VF) tests at baseline visits. Among these, one cluster demonstrated a significantly better response to ocular hypotensive medication compared to the others. Key distinguishing characteristics of this cluster included a lower frequency of family history of glaucoma (p = 0.006) but a higher prevalence of heart disease (p < 0.001) and high blood pressure (p < 0.001). Interestingly, although eyes in this cluster had a worse baseline MD than those in all other clusters (– 2.2 ± 0.1 dB vs. + 0.47 ± 1.2 dB, p < 0.001) and patients were older (64.3 ± 9.5 vs. 54.7 ± 8.94 years, p < 0.001), this was the only cluster where the MD progression rate in the treatment (active) group was significantly lower than in the observation group (+ 0.04 dB/year vs. − 0.09 dB/year, p = 0.03). Furthermore, treated eyes in this cluster had a significantly better MD progression rate than treated eyes in all other clusters (+ 0.04 dB/year vs. − 0.07 dB/year, p < 0.001). Conclusions: We identified a subtype of ocular hypertensive eyes in the OHTS that showed a better response to topical hypotensive medications, as indicated by the least risk of progression.