Simplified, Readily Available Method for the Treatment of Band Keratopathy With Ethylenediaminetetraacetic Acid : Cornea

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Simplified, Readily Available Method for the Treatment of Band Keratopathy With Ethylenediaminetetraacetic Acid

Narvaez, Julio MD*,†; Chang, Matthew BS; Ing, Jeffrey MD; De Chance, Daniel§; Narvaez, Joshua J.*

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Cornea 40(10):p 1360-1362, October 2021. | DOI: 10.1097/ICO.0000000000002635


Calcific band keratopathy (CBK) is a degenerative condition of the cornea that primarily affects Bowman layer. Fine grayish-white calcium opacities form a horizontal band toward the central cornea and, as the condition progresses, can cause loss of vision and increased glare and result in corneal erosion-like symptoms and ulceration.1 A variety of conditions increase susceptibility to CBK: corneal exposure, calcium-phosphate imbalance, alteration in tear osmolality, alkalosis, and chronic ocular inflammation.2

Ethylenediaminetetraacetic acid (EDTA) is the most widely used method of treating CBK.3 EDTA is a chelating agent that is commonly used as a food additive and in cosmetic products and can also be found in standard blood collection tubes where it is used as an anticoagulant. EDTA for ophthalmic use was originally derived from Na2EDTA but that formulation has lost approval from the FDA and can now only be obtained at specially equipped compounding pharmacies. It is recommended to treat CBK with a 3% to 4% solution of disodium EDTA (concentration = 30–40 mg/mL).4

Lee et al5 proposed a novel and useful method of producing EDTA by dissolving the K2EDTA lining found in blood collection tubes. Using this method, the authors discovered that, although effective, preparation was complex, relatively time consuming, and yielded only a small amount of useable solution due to transfer loss through 5 different tubes. This often necessitated repeating the process to obtain enough EDTA solution to treat a patient. We sought to create a protocol that created an EDTA solution of at least the currently accepted concentration that was easier and faster to create than the previously published protocol. We tested the method of Lee et al and 2 other methods of producing a solution of EDTA for treatment of CBK and found one that is significantly faster and simpler yet yields an effective concentration of EDTA with a larger volume to allow for multiple applications.


We compared 3 methods of EDTA preparation. In method 1, outlined by Lee et al, 0.3 mL of sterile water was injected into a purple-topped 3-mL K2EDTA Vacutainer blood collection tube (Becton, Dickinson and Company, Franklin Lakes, NJ) containing 5.4 mg of K2EDTA. The diluent was swirled to dissolve the K2EDTA coating the inside of the tube. The solution was then transferred from tube to tube, and the process was repeated for 5 tubes.5 The end solution volume was measured after repeating the process 5 different times.

In method 2, 0.3 mL of sterile water was injected into a single 10-mL K2EDTA Vacutainer blood collection tube containing 18 mg of K2-EDTA was used (Becton, Dickinson and Company) and swirled to dissolve the K2EDTA coating the inside of the tube. In method 3, the tube cap was removed, and 0.3 mL of sterile water was injected into the 10-mL K2EDTA tube containing 18 mg of K2EDTA, then a sterile, dry cotton–tipped applicator was used to absorb the fluid in the tube before then sweeping along the entire interior surface of the tube to dissolve the K2EDTA coating the inside (see Video, Supplemental Digital Content 1,, which demonstrates method 3). The end point was absence of a gritty sensation from the K2EDTA salt as the cotton-tipped applicator rubbed and dissolved the EDTA.

Ten trials were repeated for each method. Osmolarity was measured with the Osmo1 Single-Sample Micro-Osmometer from Advanced Instruments (Norwood, MA). Residual fluid at the bottom of the tubes was sampled in all 3 methods. The preparation time for each of the 10 trials in the 3 different methods was also measured. The results were averaged within their respective method. Differences between the 3 methods were analyzed using ANOVA and Tukey honestly significant difference (HSD) tests from for post hoc analysis.

Method 3 had the best characteristics for clinical use, and it was used in a series of patients who gave informed consent for treatment of their band keratopathy. This study conformed to the ethical principles found in the Declaration of Helsinki.


Using method 1, the average osmolarity was 531.7 mOsm/L (SD = 34.3; calculated concentration: 65.30 mg/mL). The preparation time took, on average, 188.7 seconds (SD = 18.9), and the average pH was 5.

Using method 2, the average preparation time was 38.4 seconds (SD = 6.6). The average osmolarity was 285.3 mOsm/L (SD = 86.7; calculated concentration 35.04 mg/mL), and the average pH was 4.25.

Using method 3, average preparation time was 83.1 seconds (SD = 8.8), and average osmolarity was 421.9 mOsm/L (SD = 67.4; calculated concentration 51.81 mg/mL); the average pH was 4.5. The results are summarized in the Table 1.

TABLE 1. - Average Osmolarity With SD, Calculated Concentration, and Preparation Time With SD for 3 Methods of Creating “Off-the-Shelf” EDTA Solution, With Standard Treatment as Comparison
Method 1 Method 2 Method 3 3% EDTA Solution
Mean osmolarity (±SD), mOsm/L 531.7 (±34.3) 285.3 (±86.7) 421.9 (±67.4) 244.29
Concentration (mg/mL)* 65.3 35.04 51.81 30
Mean preparation time (±SD) (s) 188.7 (±18.9) 38.4 (±6.6) 83.1 (±8.8)
*Osmolarity was converted to concentration of EDTA in mg/mL using the equation: mOsm/L × 1/3 × 368.42 mg/mmol × 1L/1000 mL.

There were significant differences when comparing osmolarity [ANOVA F(2,27) = 34.5, P < 0.01; Tukey HSD, all P < 0.01] and preparation time (ANOVA F(2,27) = 374.6, P < 0.01; Tukey HSD, all P < 0.01) between the 3 methods. We found clinically significant differences in preparation time between methods 1 and 3, but no clinically significant differences in concentration between methods 1 and 3.

Method 1 had an average yield of 0.24 mL of solution. Method 3 had, on average, 25% more volume for clinical use than method 1.

All patients treated with method 3 experienced no complications, and no delayed healing. Figure 1 shows photographs of 1 patient before and after treatment with EDTA produced with method 3. Uncorrected visual acuity before and after chelation therapy for our series of patients is summarized in Table 2.

Photographs before (left) and after (right) treatment with EDTA derived from method 3.
TABLE 2. - Visual Acuity Before and After EDTA Chelation for Band Keratopathy With Patients’ Age, Sex, and Diagnoses
Patient Demographic, Age/Sex Eye Affected Preoperative Visual Acuity Postoperative Visual Acuity Diagnosis
77/Female OS Light perception Counting finger CRVO
63/Female OD Light perception Light perception Dense cataract
49/Male OU Count finger OU 20/100 OD, 20/80 OS Stage V CKD, T1DM
85/Male OD Count finger Count finger S/p corneal transplant
77/Female OS 20/40 20/40 Keratoconjunctivitis sicca, glaucoma
CKD, chronic kidney disease; CRVO, central retinal vein occlusion; s/p, status post; T1DM, type 1 diabetes mellitus.


K2EDTA has been shown to be an effective alternative to Na2EDTA, which is both expensive and inconvenient to obtain. It is also cost-effective and widely available. At the time of writing, we found that the average cost of an ophthalmic preparation of Na2EDTA was $117 (range $70–$195), whereas 10-mL blood collection tubes cost $35.99 to $46.99 per 100 tubes.

Method 1 for producing K2EDTA as outlined by Lee et al took a substantial amount of time and had the greatest complexity. It had the highest concentration solution but less volume for use. Method 2 was the fastest to prepare but yielded the lowest concentration of K2EDTA. Method 3 struck a good balance with a greatly reduced the preparation time, greater simplicity of preparation, while achieving a higher concentration of EDTA than that commonly used to treat CBK (3%–4% disodium EDTA with concentration of 30–40 mg/mL).4 Method 3 also yielded greater volumes of solution than that by method 1, because method 1 requires transfer of fluid between 5 different vials, and residual fluid remains in the walls of the vials after transfer that cannot be retrieved. Method 3, most importantly, had good clinical efficacy. We found its clinical effectiveness indistinguishable from our previous clinical experience with method 1, and our impression is that both methods 1 and 3 are considerably faster in removing CBK than using the standard compounded 3% EDTA.


The authors wish to acknowledge Roberta Pearce, CLS (ASCP), Chemistry Supervisor and POC Coordinator at Dignity Health, St. Joseph's Medical Center, for allowing use of the osmometer for this study.


1. Al-Hity A, Ramaesh K, Lockington D. EDTA chelation for symptomatic band keratopathy: results and recurrence. Eye (Lond). 2018;32:26–31.
2. Jhanji V, Rapuano CJ, Vajpayee RB. Corneal calcific band keratopathy. Curr Opin Ophthalmol. 2011;22:283–289.
3. Bokosky JE, Meyer RF, Sugar A. Surgical treatment of calcific band keratopathy. Ophthalmic Surg. 1985;16:645–647.
4. Bagheri N, Wajda BN; Wills Eye Hospital (Philadeplphia, PA). Chapter 4 cornea: 4.10 band keratopathy. In: The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease. 7th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2017:64–65.446.
5. Lee ME, Ouano DP, Shapiro B, et al. “Off-the-Shelf” K2-EDTA for calcific band keratopathy. Cornea. 2018;37:916–918.

band keratopathy; EDTA; ethylenediaminetetraacetic acid; chelation; treatment

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Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.