title: Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01609881.
authors: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Scott D
authors: SD
authors: Schoenberger
authors: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Stephen J
authors: SJ
authors: Kim
authors: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Rohan
authors: R
authors: Shah
authors: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Jinsong
authors: J
authors: Sheng
authors: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Edward
authors: E
authors: Cherney
mesh_terms: D000287:Administration, Topical; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D020911:Ketorolac Tromethamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011446:Prospective Studies; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C508606:CXCL8 protein, human; D016209:Interleukin-8; D009883:Ophthalmic Solutions; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D020911:Ketorolac Tromethamine; D015232:Dinoprostone