Skip to main content

Advertisement

Log in

Acute and chronic optic nerve head biomechanics and intraocular pressure changes in patients receiving multiple intravitreal injections of anti-VEGF

  • Glaucoma
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate acute and chronic changes in optic nerve head (ONH) structures and intraocular pressure (IOP) in patients receiving intravitreal injections (IVIs) of anti-VEGF.

Methods

Twenty-nine eyes receiving IVIs for the first time were studied. IOP, retinal nerve fiber layer (RNFL) thickness, and ONH structures were evaluated by Spectralis optical coherence tomography with enhanced depth imaging technology. Structures were measured before and 5 min after each one of the three monthly injections of a loading dose treatment. In 13 eyes (44.8%) with more than six IVIs, another evaluation pre and immediately postinjection was performed after 1 year.

Results

A significant acute and transient IOP increase (all p ≤ 0.001), Bruch’s membrane opening (BMO) enlargement (p ≤ 0.001), cup widening (p < 0.05) and deepening (p ≤ 0.001), and prelaminar tissue thinning (p ≤ 0.001) were observed 5 min after each injection. Compared with baseline values, a significant BMO expansion (p = 0.001) and RNFL thinning (p < 0.001) were observed in the third month. In eyes with more than six IVIs, similar immediate postinjection changes, including IOP increase (p = 0.001), prelaminar tissue thinning (p = 0.007), and cup deepening (p = 0.012) were observed at 1 year, while BMO expansion was not significant (p = 0.556). Compared with baseline preinjection values, a significant BMO expansion (p = 0.003), prelaminar tissue thinning (p = 0.011), and cup deepening (p = 0.006) in the inferior region of the ONH occurred. No change in IOP was observed at the end of follow-up.

Conclusions

Repeated IVIs could lead to irreversible changes in ONH structures. Large-scale, prospective studies are required to determine the long-term effects of anti-VEGF treatments in ONH tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schlingemann R, Witmer A (2009) Treatment of retinal diseases with VEGF antagonists. Prog Brain Res 175:253–267. https://doi.org/10.1016/S0079-6123(09)17517-9

    Article  CAS  PubMed  Google Scholar 

  2. Falkenstein I, Cheng L, Freeman W (2007) Changes of intraocular pressure after intravitreal injection of bevacizumab (Avastin). Retina 27:1044–1047

    Article  PubMed  Google Scholar 

  3. Kim J, Mantravadi A, Hur E, Covert D (2008) Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol 146:930–934. https://doi.org/10.1016/j.ajo.2008.07.007

    Article  CAS  PubMed  Google Scholar 

  4. Bakri S, Pulido J, McCannel C et al (2009) Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab. Eye 23:181–185

    Article  CAS  PubMed  Google Scholar 

  5. Kotliar K, Maier M, Bauer S, Al E (2007) Effect of intravitreal injections and volume changes on intraocular pressure: clinical results and biomechanical model. Acta Ophthalmol Scand 85:777–781

    Article  PubMed  Google Scholar 

  6. Rebolleda G, Puerto B, de Juan V et al (2016) Optic nerve head biomechanic and IOP changes before and after the injection of aflibercept for neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 57:5688–5695. https://doi.org/10.1167/iovs.16-20111

    Article  CAS  PubMed  Google Scholar 

  7. Bakri S, McCannel C, Edwards A, Moshfeghi D (2008) Persistent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol 246:955–958. https://doi.org/10.1007/s00417-008-0819-2

    Article  CAS  PubMed  Google Scholar 

  8. Adelman R, Zheng Q, Mayer H (2010) Persistent ocular hypertension following intravitreal bevacizumab and ranibizumab injections. J Ocul Pharmacol Ther 26:105–110. https://doi.org/10.1089/jop.2009.0076

    Article  CAS  PubMed  Google Scholar 

  9. Good T, Kimura A, Mandava N, Kahook M (2011) Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthalmol 95:1111–1114. https://doi.org/10.1136/bjo.2010.180729

    Article  PubMed  Google Scholar 

  10. Mathalone N, Arodi-Golan A, Sar S, Al E (2012) Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 250:1435–1440. https://doi.org/10.1007/s00417-012-1981-0

    Article  CAS  PubMed  Google Scholar 

  11. Tseng J, Vance S, Della Torre K, Al E (2012) Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. J Glaucoma 21:241–247. https://doi.org/10.1097/IJG.0b013e31820d7d19

    Article  PubMed  Google Scholar 

  12. Bakri S, Moshfeghi D, Francom S et al (2014) Intraocular pressure in eyes receiving monthly ranibizumab in 2 pivotal age-related macular degeneration clinical trials. Ophthalmology 121:1102. https://doi.org/10.1016/j.ophtha.2013.11.029

    Article  PubMed  Google Scholar 

  13. Eadie B, Etminan M, Carleton B et al (2017) Association of repeated intravitreous bevacizumab injections with risk for glaucoma surgery. JAMA Ophthalmol 135:363–368. https://doi.org/10.1001/jamaophthalmol.2017.0059

    Article  PubMed  PubMed Central  Google Scholar 

  14. Atchison E, Wood K, Mattox C et al (2018) The real-world effect of intravitreous anti-vascular endothelial growth factor drugs on intraocular pressure: an analysis using the IRIS registry. Ophthalmology 125:676–682. https://doi.org/10.1016/j.ophtha.2017.11.027

    Article  PubMed  Google Scholar 

  15. Lee E, Kim T, Weinreb R et al (2011) Visualization of the lamina cribrosa using enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 152:87–95. https://doi.org/10.1016/j.ajo.2011.01.024

    Article  PubMed  Google Scholar 

  16. Liu J, He X (2009) Corneal stiffness affects IOP elevation during rapid volume change in the eye. Invest Ophthalmol Vis Sci 50:2224–2229. https://doi.org/10.1167/iovs.08-2365

    Article  PubMed  Google Scholar 

  17. Morris H, Tang J, Cruz Perez B et al (2013) Correlation between biomechanical responses of posterior sclera and IOP elevations during micro intraocular volume change. Invest Ophthalmol Vis Sci 54:7215–7222. https://doi.org/10.1167/iovs.13-12441

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sigal I, Grimm J, Jan N et al (2014) Eye-specific IOP-induced displacements and deformations of human lamina cribrosa. Invest Ophthalmol Vis Sci 55:1–15. https://doi.org/10.1167/iovs.13-12724

    Article  PubMed  PubMed Central  Google Scholar 

  19. Downs J, Roberts M, Burgoyne C (2008) Mechanical environment of the optic nerve head in glaucoma. Optom Vis Sci 85:425–435. https://doi.org/10.1097/OPX.0b013e31817841cb

    Article  PubMed  PubMed Central  Google Scholar 

  20. Shelton L, Rada J (2007) Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts. Exp Eye Res 84:314–322

    Article  CAS  PubMed  Google Scholar 

  21. Wang G, Chen W (2012) Effects of mechanical stimulation on viscoelasticity of rabbit scleral fibroblasts after posterior scleral reinforcement. Exp Biol Med 237:1150–1154. https://doi.org/10.1258/ebm.2012.012196

    Article  CAS  Google Scholar 

  22. Goktas A, Goktas S, Atas M et al (2013) Short-term impact of intravitreal ranibizumab injection on axial ocular dimension and intraocular pressure. Cutan Ocul Toxicol 32:23–26. https://doi.org/10.3109/15569527.2012.696569

    Article  CAS  PubMed  Google Scholar 

  23. Gismondi M, Salati C, Salvetat M et al (2009) Short term effect of intravitreal injection of ranibizumab (Lucentis) on intraocular pressure. J Glaucoma 18:658–661. https://doi.org/10.1097/IJG.0b013e31819c4893

    Article  PubMed  Google Scholar 

  24. Menzel C, Kotliar K, Lanzl I (2009) Retrospective investigation of seasonal factors influencing intraocular pressure in glaucoma patients. Ophthalmologe 106:1006–1011. https://doi.org/10.1007/s00347-008-1882-0

    Article  CAS  PubMed  Google Scholar 

  25. Qureshi I, Xiao R, Yang B et al (1999) Seasonal and diurnal variations of ocular pressure in ocular hypertensive subjects in Pakistan. Singap Med J 40:345–348

    CAS  Google Scholar 

  26. Cacciamani A, Oddone F, Parravano M et al (2013) Intravitreal injection of bevacizumab: changes in intraocular pressure related to ocular axial length. Jpn J Ophthalmol 57:63–67. https://doi.org/10.1007/s10384-012-0194-8

    Article  CAS  PubMed  Google Scholar 

  27. Radius R (1981) Regional specificity in anatomy at the lamina cribrosa. Arch Ophthalmol 99:478–480

    Article  CAS  PubMed  Google Scholar 

  28. Quigley H, Addicks E (1981) Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthalmol 99:137–143

    Article  CAS  PubMed  Google Scholar 

  29. Winkler M, Jester B, Nien-Shy C et al (2010) High resolution three-dimensional reconstruction of the collagenous matrix of the human optic nerve head. Brain Res Bull 81:339–348

    Article  CAS  PubMed  Google Scholar 

  30. Roberts M, Liang Y, Sigal I, Al E (2010) Correlation between local stress and strain and lamina cribrosa connective tissue volume fraction in normal monkey eyes. Invest Ophthalmol Vis Sci 51:295–307. https://doi.org/10.1167/iovs.09-4016

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bracha P, Moore N, Ciulla T et al (2018) The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: a review. Surv Ophthalmol 63:281–295. https://doi.org/10.1016/j.survophthal.2017.08.008

    Article  PubMed  Google Scholar 

  32. Hoguet A, Chen P, Junk A et al (2019) The effect of anti-vascular endothelial growth factor agents on intraocular pressure and glaucoma: a report by the american academy of ophthalmology. Ophthalmology 126:611–622. https://doi.org/10.1016/j.ophtha.2018.11.019

    Article  PubMed  Google Scholar 

  33. Shin H, Kim S, Chung H et al (2016) Intravitreal anti-vascular endothelial growth factor therapy and retinal nerve fiber layer loss in eyes with age-related macular degeneration: a meta-analysis. Invest Ophthalmol Vis Sci 57:1798–1806. https://doi.org/10.1167/iovs.15-18404

    Article  CAS  PubMed  Google Scholar 

  34. Soheilian M, Karimi S, Montahae T et al (2017) Effects of intravitreal injection of bevacizumab with or without anterior chamber paracentesis on intraocular pressure and peripapillary retinal nerve fiber layer thickness: a prospective study. Graefes Arch Clin Exp Ophthalmol 255:1705–1712. https://doi.org/10.1007/s00417-017-3702-1

    Article  CAS  PubMed  Google Scholar 

  35. Martinez-de-la-Casa J, Ruiz-Calvo A, Saenz-Frances F et al (2012) Retinal nerve fiber layer thickness changes in patients with age-related macular degeneration treated with intravitreal ranibizumab. Invest Ophthalmol Vis Sci 53:6214–6218. https://doi.org/10.1167/iovs.12-9875

    Article  CAS  PubMed  Google Scholar 

  36. Horsley M, Mandava N, Maycotte M, Kahook M (2010) Retinal nerve fiber layer thickness in patients receiving chronic anti-vascular endothelial growth factor therapy. Am J Ophthalmol 150:558–561. https://doi.org/10.1016/j.ajo.2010.04.029

    Article  CAS  PubMed  Google Scholar 

  37. Shin H, Shin K, Chung H, Kim H (2014) Change of retinal nerve fiber layer thickness in various retinal diseases treated with multiple intravitreal antivascular endothelial growth factor. Invest Ophthalmol Vis Sci 55:2403–2411. https://doi.org/10.1167/iovs.13-13769

    Article  PubMed  Google Scholar 

  38. Zucchiatti I, Cicinelli M, Parodi M et al (2017) Effect of intravitreal ranibizumab on ganglion cell complex and peripapillary retinal nerve fiber layer in neovascular age-related macular degeneration using spectral domain optical coherence tomography. Retina 37:1314–1319. https://doi.org/10.1097/IAE.0000000000001360

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Gómez-Mariscal.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the current study were in accordance with the ethical standards of Institutional Research Ethics Committee of Ramón y Cajal University Hospital and with the tenets of 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gómez-Mariscal, M., Puerto, B., Muñoz-Negrete, F.J. et al. Acute and chronic optic nerve head biomechanics and intraocular pressure changes in patients receiving multiple intravitreal injections of anti-VEGF. Graefes Arch Clin Exp Ophthalmol 257, 2221–2231 (2019). https://doi.org/10.1007/s00417-019-04354-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-019-04354-7

Keywords

Navigation