Purpose This proof-of-concept study aimed to detect preliminary signals of efficacy and assess the short-term safety of Esculin and Digitalis glycoside eye drops for the management of presbyopia. Methods This study was a 30-day, randomized, double-blind, controlled clinical trial. A total of 62 patients with presbyopia were recruited from the Ophthalmology Hospital in Shanxi Province, China, and randomly assigned to either the treatment group (n = 31) or the vehicle group (n = 31). Participants applied Esculin and Digitalis glycosides Eye Drops or the vehicle three times daily for 30 days. Efficacy and safety assessments were conducted separately under photopic and mesopic conditions at multiple time points on Days 5, 15, and 30. The Near Activity Vision Questionnaire (NAVQ) was used to assess the severity of near vision difficulties and patient satisfaction in presbyopic individuals. The primary and key secondary efficacy endpoints were defined as the percentage of participants demonstrating ≥ 3 lines improvement in distance-corrected near visual acuity (DCNVA) without a loss of one or more lines in corrected-distance visual acuity (CDVA) at 1.5 h and 0.5, 3 h post-dose 1 on Day 30, separately under photopic and mesopic conditions. Results Of the 62 randomized participants, 23 (37.10%) were male and 39 (62.90%) were female. The mean (SD) age was 50.29 (3.12) years. In the prespecified analysis, the treatment group showed a nominally statistically significant improvement in the photopic DCNVA endpoint (the proportion of participants achieving ≥ 3 lines without CDVA loss) compared to vehicle. At 0.5 h on Day 30, the percentage was 25.81% versus 6.45% (difference, 19.36%; 95% CI, 1.00% to 37.00%; p = 0.04); at hour 1.5, the percentage was 25.81% versus 3.23%, respectively (difference, 22.58%; 95% CI, 2.00% to 42.00%; p = 0.03); and at hour 3, the percentage was 25.81% versus 6.45%, respectively (difference, 19.36%; 95% CI, 1.00% to 37.00%; p = 0.04). However, no such statistically significant signal was detected under mesopic conditions. In the exploratory analysis of the prespecified photopic endpoint, the treatment group showed a nominal statistically significant improvement in mean DCNVA compared to the vehicle group at all tested time points (0.5, 1.5, and 3 h) on Day 30, at 0.5 h (mean difference, -0.06; 95% CI, -0.13 to -0.03; p < 0.01), at 1.5 h (mean difference, -0.08; 95% CI, -0.11 to -0.01; p = 0.02), at 3 h (mean difference, -0.05; 95% CI, -0.09 to -0.01; p = 0.04). No serious adverse events were reported during the 30-day study period. Treatment-related adverse events were generally mild and did not necessitate therapeutic intervention. Conclusion In this exploratory study, prespecified analysis showed a statistically significant improvement in the photopic near visual acuity endpoint for Esculin and Digitalis glycosides Eye Drops compared to vehicle at Day 30, with a favorable short-term safety profile. These findings suggest a potential benefit that warrants further investigation in larger, confirmatory trials, but they do not yet support broad clinical recommendations. This trial was registered at ClinicalTrials. gov (NCT07151612). The trial was registered on 2 September 2025.

Safety and efficacy of Esculin and Digitalis glycosides eye drops in individuals with presbyopia

期刊论文
发表日期：

2026年3月23日

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Yu Zhang,
Junfeng Wang,
Min Hao,
Chen Wang,
Xiaowei Zhang

摘要

Purpose

This proof-of-concept study aimed to detect preliminary signals of efficacy and assess the short-term safety of Esculin and Digitalis glycoside eye drops for the management of presbyopia.

Methods

This study was a 30-day, randomized, double-blind, controlled clinical trial. A total of 62 patients with presbyopia were recruited from the Ophthalmology Hospital in Shanxi Province, China, and randomly assigned to either the treatment group (n = 31) or the vehicle group (n = 31). Participants applied Esculin and Digitalis glycosides Eye Drops or the vehicle three times daily for 30 days. Efficacy and safety assessments were conducted separately under photopic and mesopic conditions at multiple time points on Days 5, 15, and 30. The Near Activity Vision Questionnaire (NAVQ) was used to assess the severity of near vision difficulties and patient satisfaction in presbyopic individuals. The primary and key secondary efficacy endpoints were defined as the percentage of participants demonstrating ≥ 3 lines improvement in distance-corrected near visual acuity (DCNVA) without a loss of one or more lines in corrected-distance visual acuity (CDVA) at 1.5 h and 0.5, 3 h post-dose 1 on Day 30, separately under photopic and mesopic conditions.

Results

Of the 62 randomized participants, 23 (37.10%) were male and 39 (62.90%) were female. The mean (SD) age was 50.29 (3.12) years. In the prespecified analysis, the treatment group showed a nominally statistically significant improvement in the photopic DCNVA endpoint (the proportion of participants achieving ≥ 3 lines without CDVA loss) compared to vehicle. At 0.5 h on Day 30, the percentage was 25.81% versus 6.45% (difference, 19.36%; 95% CI, 1.00% to 37.00%; p = 0.04); at hour 1.5, the percentage was 25.81% versus 3.23%, respectively (difference, 22.58%; 95% CI, 2.00% to 42.00%; p = 0.03); and at hour 3, the percentage was 25.81% versus 6.45%, respectively (difference, 19.36%; 95% CI, 1.00% to 37.00%; p = 0.04). However, no such statistically significant signal was detected under mesopic conditions. In the exploratory analysis of the prespecified photopic endpoint, the treatment group showed a nominal statistically significant improvement in mean DCNVA compared to the vehicle group at all tested time points (0.5, 1.5, and 3 h) on Day 30, at 0.5 h (mean difference, -0.06; 95% CI, -0.13 to -0.03; p < 0.01), at 1.5 h (mean difference, -0.08; 95% CI, -0.11 to -0.01; p = 0.02), at 3 h (mean difference, -0.05; 95% CI, -0.09 to -0.01; p = 0.04). No serious adverse events were reported during the 30-day study period. Treatment-related adverse events were generally mild and did not necessitate therapeutic intervention.

Conclusion

In this exploratory study, prespecified analysis showed a statistically significant improvement in the photopic near visual acuity endpoint for Esculin and Digitalis glycosides Eye Drops compared to vehicle at Day 30, with a favorable short-term safety profile. These findings suggest a potential benefit that warrants further investigation in larger, confirmatory trials, but they do not yet support broad clinical recommendations.

This trial was registered at ClinicalTrials. gov (NCT07151612). The trial was registered on 2 September 2025.