Penetration of topically applied diclofenac and ketorolac into the aqueous humour and subretinal fluid: randomized clinical trial

Can J Ophthalmol. 2010 Dec;45(6):610-5. doi: 10.3129/i10-048.


Objective: To determine the level of intraocular penetration of diclofenac sodium and ketorolac tromethamine into the aqueous humour and subretinal fluid.

Design: Prospective randomized clinical trial.

Participants: Twenty eyes scheduled for retinal detachment surgery and 17 eyes scheduled for cataract surgery.

Methods: Patients with retinal detachment were randomly assigned to receive either topical ketorolac (n = 11) or topical diclofenac (n = 9). Subretinal fluid samples were collected 30-60 minutes after the administration of the last dose. In addition, 17 patients with cataract were randomly assigned to receive topical ketorolac (n = 9) or topical diclofenac (n = 8). The aqueous humour samples were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography fluorescence.

Results: The mean diclofenac concentration in the subretinal fluid was 42.31 (SD 24.89) ng/µL. Ketorolac was undetectable in the subretinal fluid in all patients who received it because ketorolac tromethamine levels were under the limit of detection. In the aqueous humour, mean diclofenac concentration was 4.98 (SD 4.56) ng/µL, and mean ketorolac concentration was 20.17 (SD 12.21) ng/µL. Topical administration of diclofenac sodium yielded 8.4 times greater drug concentration in the subretinal fluid than in the aqueous humour. Aqueous humour concentrations of ketorolac were higher than those of diclofenac (p = 0.019).

Conclusions: The concentration in the subretinal fluid of topically applied diclofenac was higher than that of ketorolac; and topical ketorolac penetrated into the aqueous humour better than diclofenac did. This suggests that diclofenac can be used more effectively in events related to posterior segment and ketorolac in anterior segment events.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Aqueous Humor / metabolism*
  • Biological Availability
  • Cataract Extraction
  • Chromatography, High Pressure Liquid
  • Diclofenac / pharmacokinetics*
  • Female
  • Humans
  • Ketorolac Tromethamine / pharmacokinetics*
  • Male
  • Middle Aged
  • Prospective Studies
  • Retinal Detachment / surgery
  • Scleral Buckling
  • Subretinal Fluid / metabolism*


  • Diclofenac
  • Ketorolac Tromethamine