Purpose: To explore the efficacy of topical 2.6% EDTA ophthalmic solution (C-KAD) as a treatment to improve visual function for the subgroup of patients with loss of contrast sensitivity (CS) due to early-stage age-related cataract., Design: Subgroup analysis of randomized, double-blinded, placebo-controlled, multicenter phase 1/2 clinical trial data., Methods: Both eyes of subjects in the intent-to-treat population, with mesopic CS scores between 1 and 7 grating patches (range 0-9, each patch representing 0.15 logCS), at baseline in all five frequencies, were included. The proportion of eyes with clinically significant mesopic CS improvement and mean changes in mesopic CS at spatial frequencies between 1.5 to 18 cycles per degree (cpd), and summary metrics of area under the log CS function (AULCSF), were analyzed. Other exploratory outcomes analyzed included best-corrected visual acuity (BCVA) and lens density for a smaller subgroup of eyes for which Scheimpflug images were available., Results: Forty-one subject eyes were included in the subgroup analysis (C-KAD n = 21, placebo n = 20). The primary endpoint of the proportion of eyes with mesopic CS improvements ≥ 0.30 logCS (equivalent to 100% CS improvement) in at least two of the five spatial frequencies was significantly greater for C-KAD (66.7% vs. 35.0% for placebo, P = .043) at Day 120. C-KAD met the primary protocol endpoint in this subgroup analysis. The proportion of eyes achieving ≥ 0.30 logCS improvement (mesopic) as measured in AULCSF was also significantly greater for C-KAD, with 42.9% compared to 15.0% for placebo (P = .050) at Day 120. The mean change in AULCSF (mesopic) was significantly larger for C-KAD, with 0.25 logCS improvement, versus placebo with 0.06 logCS improvement (P = .020) at Day 120. C-KAD also showed significant mesopic CS improvements at spatial frequencies 3 and 6 cpd, with 0.28 logCS (P = .004) and 0.31 logCS (P = .047) versus placebo at Day 120. Positive BCVA trends and statistical significance in lens density were also observed., Conclusions: A significant treatment effect of C-KAD in visual function and vision quality was observed consistently. These promising results suggest a novel, noninvasive pharmacological treatment to improve vision in patients with early-stage cataract., (Copyright © 2024 Elsevier Inc. All rights reserved.)