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Changing the composition of buffered eye-drops prevents undesired side effects
  1. Norbert F Schrage1,2,3,
  2. Markus Frentz2,
  3. Martin Reim3
  1. 1Department of Ophthalmology, Hospital Cologne-Merheim, Cologne, Germany
  2. 2Aachen Center of Technology Transfer in Ophthalmology, Aachen, Germany
  3. 3Department of Ophthalmology Aachen University, Aachen, Germany
  1. Correspondence to Professor Dr Norbert F Schrage, ACTO eV, Karlsburgweg 9, Aachen 52070, Germany; schrage{at}


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.

  • Cornea
  • calcification
  • phosphate
  • side effects
  • citrate buffer
  • hyaluronic acid
  • healing
  • wound healing
  • diagnostic tests/investigation
  • experimental & laboratory

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  • Funding This work was partially supported by Ursapharm Arzneimittel GmbH & Co KG, Saarbrücken, Germany, who supplied the hyaluronate eye-drops containing citrate. Staff costs, equipment and other materials were financed by ACTO eV, and by the Department of Ophthalmology, University Hospital, Aachen, Germany.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.