Does intravitreal injection of aflibercept affect the corneal endothelium?

Does intravitreal injection of aflibercept affect the corneal endothelium?

Aim: To evaluate the effect of intravitreal aflibercept injections on the corneal endothelium in patients with exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and central retinal vascular occlusion (CRVO). Materials and Methods: The study included 50 eyes of 44 patients who underwent three consecutive intravitreal aflibercept injections with the diagnosis of AMD, DME or CRVO. All patients underwent complete ophthalmological examination and specular microscopy at pre-injection and at one month after the third injection. The pre-injection and post-injection values of endothelial cell density (CD), coefficient of variation (CoV), hexagonality (Hex), central corneal thickness (CCT), and intraocular pressure (IOP) were compared statistically. Results: The mean age of the patients was 71.09 ± 5.6 (40–87) years. Thirty-six eyes had exudative AMD, 10 had DME and 4 had CRVO. There were no significant differences in CD, CoV, Hex, CCT, and IOP between the pre-injection and post-injection measurements. However, in patients with AMD, the mean pre-injection CD was 2439.71 ± 476.16 cells/mm2 and the mean post-injection CD was 2286.18 ± 427.24 cells/mm2. CD values were decreased in the AMD group, but this difference was not statistically significant (p = 0.061). In patients with AMD, the mean pre-injection and post-injection CCT values were 536.1 ± 28.4 μm and 542.5 ± 32.9 μm, respectively, and the difference was statistically significant (p = 0.04). Conclusion: Intravitreal aflibercept injection had no manifest devastating effects on the corneal endothelium. However, the decreasing number of endothelial cells with age may be susceptible to aflibercept injection.

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  • 1. Marneros AG. Role of VEGF-A in aging disease of the eye. EMBO Mol Med 2016;8:208-31.
  • 2. Yeh S, Kim SJ, Ho AC, et al. Therapies for macular edema associated with central vein occlusion: a report by the American Academy of Ophthalmology. Ophthalmology 2015;122:769-78
  • 3. Kucukerdonmez C, Gelisken F, Yoeruek E, et al. Switching intravitreal anti-VEGF treatment in neovasculer age-related macular degeneration. Eur J Ophthalmol 2015;25:51-6.
  • 4. Avery LR, Castellarin AA, Steinle NC, et al. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab and ranibizumab. Retina 2017;37:1847-58.
  • 5. Kucumen RB, Yenerel NM. Diabetic macular edema and its treatment modal ities. Turk J Ophthalmol 2012;42:53-60.
  • 6. Ricca A, Wirostko B. Ocular hypertension following intravitreal antivascular endothelial growth factor therapy: review of the literature and possible role of nitric oxide. J Glaucoma 2016;25:291-300.
  • 7. Falavarjani KG, QD Nguyen. Adverse events and complications associated with intravitreal injection of anti-VEGF agents:a review of literature. Eye 2013;27:787-94.
  • 8. Ozcaliskan S, Yilmazbas P, Ozturk F, et al. The short- term effect of intravitreal bevacizumab injection on intraocular pressure. Turk J Ophthalmol 2014;44:361- 4.
  • 9. Campa C. Effect of VEGF and anti-VEGF compounds on retinal pigment epithelium permeability: an in vitro study. Eur J Ophthalmol 2013;23:690-6.
  • 10. Miura Y, Klettner A, Roider J. VEGF antagonists decrease barrier function of retinal pigment epithelium in vitro: possible participation of intracellular glutathione. Invest Ophthalmol Vis Sci 2010;51:4848- 55.
  • 11. Forrester J, Dick A, McMenamin P, et al. General and ocular pharmacology. In: Forrester J, Dick A, McMenamin P, Roberts F, Pearlman E, eds. The Eye: Basic Science in Practice. 4th edition. London: WB Saunders; 2015 p. 338-69.
  • 12. Philipp W, Speicher L, Humpel C. Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci 2000;41:2514-22.
  • 13. Niwa Y, Kakinoki M, Sawada T, et al. Ranibizumab and aflibercept: intraocular pharmacokinetics and their effects on aqueous VEGF level in vitrectomized and nonvitrectomized macaques eyes. Invest Ophthalmol Vis Sci 2015;56:6501-5.
  • 14. Gan L, Fagerholm P, Palmblad J. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing. Acta Ophthalmol Scand 2004;82:557-63.
  • 15. Gharbiya M, Bruscolini A, Sacchetti M, et al. In vivo antivascular endothelial growth factor treatment induces corneal endothelium apoptosis in rabbits through changes in p75NTR-proNGF pathway. J Cell Physiol 2018;233:8874-83.
  • 16. Akal A, Ulas T, Goncu T, et al. Evaluating the safety of intracameral bevacizumab application using oxidative stress and apoptotic parameters in corneal tissue. Int J Ophthalmol 2015;8:697-702.
  • 17. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012;119:2537-48.
  • 18. Faragher RG, Mulholland B, Tuft SJ, et al. Aging and the cornea. Br J Ophthalmol 1997;81:814-7.
  • 19. Utine CA. Specular microscopy and confocal microscopy mechanism of action and application in ophthalmology: Review. Turkiye Klinikleri J Ophthalmol 2011;20:89-98.
  • 20. Zavala J, Lopez Jaime GR, Rodriguez Barrienos CCA, et al. Corneal endothelium: developmental strategies for regeneration. Eye 2013;27:579-88.
  • 21. Kim JE, Mantravadi AV, Hur EY, et al. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol 2008;146:930- 4.
  • 22. Lee JW, Park H, Choi JH, et al. Short-term changes of intraocular pressure and ocular perfusion pressure after intravitreal injection of bevacizumab or ranibizumab. BMC Ophthalmol 2016;16:255-8.
  • 23. Franco S, Lira M. Biomechanical properties of the cornea measured by the oculer response analyser and their association with intraoculer pressure and central corneal curvature. Clin Exp Optom 2009;92:469-75.
  • 24. Ucgul Atilgan C, Kosekahya P, Ozkoyuncu Kocabas D, et al. Densitometric analysis of cornea in patients with neovascular age-related macular degeneration after intravitreal aflibercept loading dose. Ther Adv Ophthalmol 2020;12:2515841420950857.
  • 25. Park JP, Lee M. Short-term effects and safety of an acute increase of intraocular pressure after intravitreal bevacizumab injection on corneal endothelial cells. BMC Ophthalmol 2018;18:17-22.
  • 26. Guzel H, Bakbak B, Koylu MT, et al. The effect and safety of intravitreal injection of ranibizumab and bevacizumab on the cornea endothelium in the treatment of diabetic macular edema. Cutan Ocu Toxicol 2017;36:5-8.
  • 27. Guler HA, Ornek N, Ornek K, et al. Effect of dexamethasone implant (Ozurdex) on corneal endothelium in retinal vein occlusion patients. BMC Opthalmology 2018;18:235-9.
  • 28. Chiang CC, Chen WL, Lin JM, et al. Effects of bevacizumab on human corneal endothelial cells. A six month follow-up study. Am J Ophthalmol 2008;146:688-91.
  • 29. Lass JH, Benetz BA, Menegay HJ, et al. Effects of repeated intravitreal aflibercept injection on the corneal endothelium in patients with age-related macular degeneration: Outcomes from the RE-VIEW Study. Cornea 2018;37:596-601.
  • 30. Muto T, Machida S. Effect of intravitreal aflibercept on corneal endothelial cells: a 6-month follow-up study. Clin Ophthalmol 2019;13:373-81.
  • 31. Arslan GD, Guven D, Alkan AA, et al. Short term effects of intravitreal anti-vascular endothelial growth factor agents on cornea, anterior chamber, and intraocular pressure. Cutan Ocul Toxicol 2019;38:344-8.
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  • Yayın Aralığı: Aylık
  • Yayıncı: İnönü Üniversitesi Tıp Fakültesi