Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies

Ophthalmology. 1999 Mar;106(3):556-63. doi: 10.1016/S0161-6420(99)90116-1.


Objectives: To investigate conjunctival and trabecular specimens from patients with glaucoma according to the duration and number of drugs received before filtration surgery, and to confirm, in a complementary experimental model, the role of preservative by comparing the effects of preserved and nonpreserved timolol.

Study design: Experimental animal and human tissue study.

Participants: Paired specimens of conjunctiva and trabeculum were taken from 61 patients undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5 underwent primary surgery. A second study was performed in 25 rats receiving topical solutions in both eyes for 1 month.

Intervention: Immunohistochemistry was performed in all biopsy specimens using 12 different monoclonal antibodies. Ocular structures from rats treated for 1 month with preserved 0.5% timolol, nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly investigated in an experimental study.

Main outcome measures: Inflammatory cell infiltrates and fibroblasts were evaluated in biopsies, as well as in animal specimens, together with histologic changes induced by the drugs applied.

Results: Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from multitreated patients were found to be abnormally infiltrated by cells expressing inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9 of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the primary surgery group were abnormal. In rats, preserved timolol and benzalkonium similarly showed infiltrates together with toxic histopathologic changes as compared to the nonpreserved timolol and control groups.

Conclusions: These two combined studies confirmed histopathologic effects of antiglaucomatous drugs on the conjunctiva and showed similar effects in the trabecular meshwork. The experimental study showed that benzalkonium chloride is at least, to a large part, responsible for these toxic or immunoinflammatory effects or both on the ocular structures.

MeSH terms

  • Administration, Topical
  • Adrenergic beta-Antagonists / adverse effects*
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Benzalkonium Compounds / adverse effects
  • Conjunctiva / drug effects*
  • Conjunctiva / pathology
  • Dendritic Cells / pathology*
  • Drug Therapy, Combination
  • Female
  • Fibroblasts / pathology
  • Fluorescent Antibody Technique, Indirect
  • Glaucoma / drug therapy
  • Glaucoma / surgery
  • Humans
  • Male
  • Middle Aged
  • Ophthalmic Solutions / adverse effects
  • Ophthalmic Solutions / therapeutic use
  • Pilocarpine / adverse effects*
  • Pilocarpine / therapeutic use
  • Preservatives, Pharmaceutical / adverse effects
  • Rats
  • Rats, Inbred BN
  • Sympathomimetics / adverse effects*
  • Sympathomimetics / therapeutic use
  • Trabecular Meshwork / drug effects*
  • Trabecular Meshwork / pathology
  • Trabeculectomy


  • Adrenergic beta-Antagonists
  • Benzalkonium Compounds
  • Ophthalmic Solutions
  • Preservatives, Pharmaceutical
  • Sympathomimetics
  • Pilocarpine