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Updated: Jun 10, 2026

Effect of Artificial Tear Formulations on the Metabolic Activity of Human Corneal Epithelial Cells after Exposure to Desiccation
Published on: May 2, 2020
Changing the composition of buffered eye-drops prevents undesired side effects
Norbert F Schrage1, Markus Frentz, Martin Reim
1Department of Ophthalmology, Hospital Cologne-Merheim, Cologne, Germany. schrage@acto.de
Purpose:
The Ex Vivo Eye Irritation Test (EVEIT) is used to analyse the clinical observations of corneal calcification attributed to the presence of phosphate within applied eye-drops used in treating glaucoma, Still-Chauffard syndrome, ocular burns and dry eyes.
Method:
Live corneas from abattoir rabbit eyes were cultured in order to study epithelial healing following mechanical abrasion of the corneal surface combined with repeated exposure to various eye-drops.
Results:
Obvious corneal calcification of the wound area along with a complete epithelial healing covering the calcified area was observed following exposure to phosphate hyaluronate eye-drops. Epithelial healing without calcification was achieved using citrate hyaluronate eye-drops.
Conclusion:
Clinical observations show that topical use of artificial tears containing phosphate on injured eyes may lead to sight-threatening corneal complications. Simulation of such treatment conditions by the EVEIT convincingly demonstrates that changes in the composition of the pharmaceutically used treatments can prevent this undesired side effect. Although considerable healing was achieved during the repeated application of eye-drops, using either a phosphate or citrate buffer, only the drops containing citrate did not develop corneal calcification on the eye. The authors therefore recommend discontinuing the use of phosphate-buffered eye-drops, or other topically applied solutions, to avoid further injury to the patient.
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Buffers
