Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy

JAMA Ophthalmol. 2014 Jan;132(1):32-7. doi: 10.1001/jamaophthalmol.2013.6203.

Abstract

Importance: Inhibition of inflammatory cytokines may have therapeutic effects in diabetic retinopathy (DR).

Objective: To compare aqueous and vitreous levels of 17 inflammatory cytokines in patients treated preoperatively with topical ketorolac tromethamine, 0.45%, or placebo before pars plana vitrectomy for complications related to proliferative DR (PDR).

Design, setting, and participants: A prospective, randomized, placebo-controlled, patient-masked interventional study performed in a university academic hospital included 20 eyes from 20 patients undergoing pars plana vitrectomy for complications of PDR.

Interventions: Eyes were randomized to ketorolac tromethamine, 0.45% (Acuvail), or placebo 4 times daily for 3 days before pars plana vitrectomy. Undiluted aqueous and vitreous samples were taken at the time of surgery and immediately frozen at -80°C.

Main outcomes and measures: Aqueous and vitreous levels of prostaglandin E2 and 16 other inflammatory cytokines implicated in the pathogenesis of DR.

Results: Prostaglandin E2, platelet-derived growth factor (PDGF) AA, eotaxin, vascular endothelial growth factor, interferon γ-inducible protein of 10 kDa, monocyte chemoattractant protein 1, growth-related oncogene, interleukin 6, interleukin 8 (IL-8), and tumor necrosis factor were detectable in the aqueous and vitreous of at least half of the eyes, and these cytokines were analyzed further. Aqueous levels were lower in the ketorolac group for all cytokines detected, but only the difference in IL-8 was statistically significant (52% reduction; P = .04). Levels of IL-8 (41% reduction; P = .002) and PDGF-AA (21% reduction; P = .009) were significantly lower in the vitreous of patients treated with ketorolac.

Conclusions and relevance: Topical ketorolac tromethamine, 0.45%, significantly lowered aqueous IL-8 levels and vitreous IL-8 and PDGF-AA levels in this series of eyes, suggesting that it may cause meaningful inhibition of inflammatory cytokines implicated in the pathogenesis of DR.

Trial registration: clinicaltrials.gov Identifier: NCT01609881.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aqueous Humor / metabolism*
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / metabolism
  • Dinoprostone / metabolism
  • Double-Blind Method
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-8 / metabolism*
  • Ketorolac Tromethamine / therapeutic use*
  • Male
  • Middle Aged
  • Ophthalmic Solutions
  • Platelet-Derived Growth Factor / metabolism*
  • Prospective Studies
  • Vitrectomy
  • Vitreous Body / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • CXCL8 protein, human
  • Interleukin-8
  • Ophthalmic Solutions
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor A
  • Ketorolac Tromethamine
  • Dinoprostone

Associated data

  • ClinicalTrials.gov/NCT01609881