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

Our aim in this work is to identify a subtype of ocular hypertensive eyes that benefited the most from topical hypertensive medication.

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.

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).

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.