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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

  • Retinal Disorders
  • Published:
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Abstract

Purpose

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.

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Abbreviations

ANGPT:

Angiopoietin

AU:

Arbitrary unit

ECM:

Extracellular matrix

MMP:

Matrix metalloproteinase

PVR:

Proliferative vitreoretinopathy

RRD:

Rhegmatogenous retinal detachment

TGF-β1:

Transforming growth factor-β1

VEGF:

Vascular endothelial growth factor

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Acknowledgments

Publication of this article was supported by grants from the Finnish Eye Foundation, The Eye and Tissue Bank Foundation, the Mary and Georg C. Ehrnrooth Foundation, the Waldemar von Frenckells Foundation, the Nissi Foundation, the Friends of the Blind, and HUCH Clinical Research Grants (TKK4150 and TYH1325).

Conflict of interest

The authors declare no conflicts of interests. The authors thank Mrs. Anna Salvato and Mrs. Paula Kaijanmäki for excellent technical assistance.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Helsinki University Central Hospital, Haartmaninkatu 4 C, FI-00290, Helsinki, Finland

    Raimo Tuuminen

  2. Hjelt Institute, Faculty of Medicine, University of Helsinki, Haartmaninkatu 4 C, FI-00290, Helsinki, Finland

    Jari Haukka

  3. Unit of Vitreoretinal Surgery, Department of Ophthalmology, Helsinki University Central Hospital, Haartmaninkatu 4 C, FI-00290, Helsinki, Finland

    Sirpa Loukovaara

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  1. Raimo Tuuminen
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Correspondence to Sirpa Loukovaara.

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Tuuminen, R., Haukka, J. & Loukovaara, S. 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. Graefes Arch Clin Exp Ophthalmol 253, 1685–1693 (2015). https://doi.org/10.1007/s00417-014-2873-2

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  • DOI: https://doi.org/10.1007/s00417-014-2873-2

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