Ocular symptoms and signs with preserved and preservative-free glaucoma medications

Eur J Ophthalmol. May-Jun 2007;17(3):341-9. doi: 10.1177/112067210701700311.


Purpose: To compare the prevalence of side effects between eyedrops with or without preservatives, in terms of subjective symptoms and objective signs in patients with open-angle glaucoma.

Methods: In a multicenter cross-sectional epidemiologic survey in four European countries, ophthalmologists in private practice enrolled 9658 nonconsecutive patients using preservative (P) or preservative-free (PF) beta-blocking eyedrops between June 1997 and December 2003. Subjective symptoms, conjunctival and palpebral signs, and superficial punctate keratitis were explored before and after a change in therapy. For statistical analysis, a Chi-square test was used to calculate the differences in the prevalence of symptoms and signs with or without preservatives.

Results: A total of 74% of the patients used P, 12% PF, 10% a P-PF combination, and in 4% the type of medication was unknown. Each recorded symptom and all the palpebral, conjunctival, and corneal signs were significantly more frequent (p<0.0001) in the P-group than in the PF-group, such as pain or discomfort during instillation (48 vs 19%), foreign body sensation (42 vs 15%), stinging or burning (48 vs 20%), and dry eye sensation (35 vs 16%). A total of 68% of the patients had a sec-ond visit performed, of whom 63% (6083) had been evaluated on treatment difference. A significant decrease (p<0.0001) of all ocular symptoms and signs was observed in patients in whom the preserved eyedrops were diminished in number or altered into preservative free drops.

Conclusions: Compared to preserved eyedrops, preservative free eyedrops are significantly less associated with ocular symptoms and signs of irritation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / adverse effects*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / adverse effects
  • Child
  • Conjunctival Diseases / chemically induced*
  • Cross-Sectional Studies
  • Eyelid Diseases / chemically induced*
  • Female
  • Glaucoma / drug therapy*
  • Humans
  • Incidence
  • Keratitis / chemically induced*
  • Male
  • Middle Aged
  • Ophthalmic Solutions / adverse effects
  • Preservatives, Pharmaceutical / adverse effects*


  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Ophthalmic Solutions
  • Preservatives, Pharmaceutical