A Comparative Analysis of Alternative Calcium Chelators for the Treatment of Calcific Band Keratopathy

Abstract

Purpose : K₃EDTA and K₂EDTA are readily available alternatives to Na₂EDTA, the traditional calcium chelator used to treat calcific band keratopathy. In this study we compare clinically relevant biochemical properties of each chelator in terms of pH, osmolarity, and calcium chelation potential.

Methods : 0.2 M Solutions of K₂EDTA (BD) and K₃EDTA (BD, obtained from vacutainer tubes) and Na₂EDTA (0.2M, Sigma Aldrich) were made. The pH of each solution was first measured (Mettler Toledo pH meter) and the theoretical osmolarity calculated with the assumption of full disassociation of EDTA salts. Next, we calculated the calcium chelation potential of each EDTA salt by titrating with 10 µmol of calcium hydroxyapatite or 10 µmol CaCl₂ containing Patton-Reeder colorimetric indicator (endpoint indicated by color shift from pink to blue). All titrations were repeated three times to obtain an average and standard deviation. Statistical significance was analyzed using Analysis of Variance (ANOVA) calculations.

Results : The 0.2 M solutions of Na₂EDTA, K₂EDTA, and K₃EDTA have pH values of 4.43, 5.71 and 9.191 and theoretical osmolarities of 600, 600, and 800 mOsm/L, respectively. Calcium chelation ability was similar among all 3 solutions: 0.94-0.98 mol of EDTA was needed to fully chelate 1 mol calcium ions of CaCl₂ (P=0.296), 0.100-0.108 mol of EDTA was needed to fully chelate 1 mol calcium ions of the hydroxyapatite aqueous suspension (P=0.296), and 0.992-0.996 mol was needed to chelate 1 mol calcium ions of hydroxyapatite in acidic solution (P=0.178, Table). Compared to the clinical standard 3% Na₂EDTA, approximately 3.3% K₂EDTA and 3.6% K₃EDTA is needed to chelate an equivalent amount of calcium.

Conclusions : Herein we provide clinically relevant biochemical properties of two alternatives to disodium EDTA and demonstrate comparable calcium chelation ability among all 3 solutions. In situations where sterile sources of Na₂EDTA is unavailable, salts of potassium EDTA may provide a convenient and equally effective method of treatment for band keratopathy.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.