title: Statins in rhegmatogenous retinal detachment are associated with low intravitreal angiopoietin-2, VEGF and MMP-2 levels, and improved visual acuity gain in vitrectomized patients.
abstract: OBJECTIVE
  In rhegmatogenous retinal detachment (RRD), intravitreal growth factors and cytokines may compromise post-vitrectomy outcomes. Here, we analysed perioperative intravitreal protein levels of potent vasoactive, pro-inflammatory, and extracellular matrix-remodelling factors in RRD eyes of patients treated with statins and evaluated post-vitrectomy outcome in the same study eyes.
  
  
  METHODS
  Institutional, retrospective, observational study of 14 patients operated on for RRD while on statins compared to patients without statin medication (n = 82). Vitreous samples were subjected to protein measurements of angiopoietin (ANGPT)-1 and -2, transforming growth factor-β1, and vascular endothelial growth factor (VEGF) by ELISA, and of matrix metalloproteinase (MMP)-2 and -9 by gelatin zymography. A 1-month best-corrected visual acuity (BCVA) gain was modelled by Student's T-test and multivariate linear regression with concomitant perioperative medication. Cumulative 12-month revitrectomy frequency was modelled by Kaplan-Meier log-rank test.
  
  
  RESULTS
  Intravitreal levels of ANGPT-2 (49.2 ± 33.1 vs. 112.8 ± 134.1 pg/ml, mean ± SD, p < 0.001), VEGF (2.3 ± 2.4 vs. 17.7 ± 57.8 pg/ml, p = 0.021), and MMP-2 (1107.1 ± 884.6 vs 1976.4 ± 970.1 AU/ml, p = 0.005) in RRD eyes of patients treated with statins were lower than in non-statin-treated controls. Patients on statins had better 1-month BCVA improvement than did those not on statins (p = 0.022), with no difference in 1-year re-vitrectomy rates.
  
  
  CONCLUSIONS
  Intravitreal levels of ANGPT-2, VEGF, factors involved in vascular permeability and inflammation, and activity of MMP-2, the factor connected with breakdown of basement membrane and fibroproliferation, were lower in RRD eyes of patients with statin treatment. At 1-month, postoperative BCVA gain was improved in statin-treated RRD eyes, suggesting that statin administration may be effective in preventing inflammation-related PVR formation.
authors.affiliation: Department of Ophthalmology, Helsinki University Central Hospital, Haartmaninkatu 4 C, FI-00290, Helsinki, Finland.
authors.forename: Raimo
authors.initials: R
authors.lastname: Tuuminen
authors.affiliation: Hjelt Institute, Faculty of Medicine, University of Helsinki, Haartmaninkatu 4 C, FI-00290, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Haukka
authors.affiliation: Unit of Vitreoretinal Surgery, Department of Ophthalmology, Helsinki University Central Hospital, Haartmaninkatu 4 C, FI-00290, Helsinki, Finland. sirpa.loukovaara@hus.fi.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Loukovaara
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000378:metabolism*; D000069059:Atorvastatin / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D012163:Retinal Detachment / Q000188:drug therapy* / Q000378:metabolism; D012189:Retrospective Studies; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014792:Visual Acuity / Q000502:physiology*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Angiopoietin-2; HMG-CoA reductase inhibitors; Inflammation; Rhegmatogenous retinal detachment; VEGF; Vitrectomy