Advertisement

Repeated intravitreal injections of antivascular endothelial growth factors and risk of intraocular pressure medication use

  • Qi N. Cui
  • Iga N. Gray
  • Yinxi Yu
  • Brian L. VanderBeekEmail author
Glaucoma
  • 70 Downloads

Abstract

Purpose

To determine the risk of initiating ocular hypertension and glaucoma treatment with repeated injections of antivascular endothelial growth factors (anti-VEGF).

Methods

A unique, retrospective cohort study was performed using a large national US medical claim database. The study population included patients who had 1 or more injections of an anti-VEGF agent. Exclusion occurred for any previous glaucoma, glaucoma suspect, glaucoma-related procedure, an ocular steroid injection, or not seeing an eye care provider at least once in each year of follow-up. Cohorts were divided into quartiles based on the number of injections performed over the follow-up period. Patients were observed for 2 and 3 years. The main outcome measure was defined as any new prescription for an ocular antihypertensive medication with a concurrent diagnosis of glaucoma, glaucoma suspect, or ocular hypertension. Multivariate logistic regression determined the odds of initiating glaucoma treatment in each injection quartile while controlling for numerous covariates. Sensitivity analysis assessed outcomes that included new medication only as well as a new medication plus diagnosis of glaucoma.

Results

In total, 17,113 and 9992 patients met 2- and 3-year observation end points, respectively. The multivariate odds ratio for initiating glaucoma treatment at 2 years was higher in the highest quartile (OR 1.96, 95% CI 1.39–2.76, p < 0.001) compared with the lowest. The 3-year comparison had similar results with increased odds in the highest quartile (OR 1.51, 95% CI 1.07–2.13, p = 0.006) compared with the lowest. Sensitivity analyses also showed similar results with more injections being associated with initiating treatment (p < 0.053 for all comparisons).

Conclusions

Repeated anti-VEGF injections are associated with an increased odds of initiating treatment for ocular hypertension and glaucoma.

Keywords

Glaucoma Anti-VEGF Intravitreal injections Epidemiology 

Notes

Funding

This study was funded by the National Institutes of Health K23 Award (1K23EY025729-01), National Institute of Healthy-National Eye Institute K12 Award (2K12EY015398-11A1; PI: Maureen Maguire), and University of Pennsylvania Core Grant for Vision Research (2P30EYEY001583). Additional funding was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. Funding from each of the above sources was received in the form of block research grants to the Scheie Eye Institute.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All analyses performed in this study involving data from humans were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was deemed exempted from IRB review by the University of Pennsylvania Institutional Review Board due to the deidentified nature of the data used within the study. The need for informed consent was also waived by the University of Pennsylvania IRB again due to the deidentified nature of the data used.

Disclosure

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. None of the organizations had any role in the design or conduction of the study.

Supplementary material

417_2019_4362_MOESM1_ESM.docx (21 kb)
Supplemental Table 1 (DOCX 20 kb)

References

  1. 1.
    Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355(14):1419–1431Google Scholar
  2. 2.
    Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355(14):1432–1444Google Scholar
  3. 3.
    Group CR, Martin DF, Maguire MG et al (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364(20):1897–1908Google Scholar
  4. 4.
    Kim JE, Mantravadi AV, Hur EY, Covert DJ (2008) Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol 146(6):930–4 e1Google Scholar
  5. 5.
    Bakri SJ, Pulido JS, McCannel CA et al (2009) Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab. Eye (Lond) 23(1):181–185Google Scholar
  6. 6.
    El Chehab H, Agard E, Russo A et al (2016) Intraocular pressure spikes after aflibercept intravitreal injections. Ophthalmologica 236(1):43–47Google Scholar
  7. 7.
    El Chehab H, Le Corre A, Agard E et al (2013) Effect of topical pressure-lowering medication on prevention of intraocular pressure spikes after intravitreal injection. Eur J Ophthalmol 23(3):277–283Google Scholar
  8. 8.
    Agard E, Elchehab H, Ract-Madoux G et al (2015) Repeated intravitreal anti-vascular endothelial growth factor injections can induce iatrogenic ocular hypertension, especially in patients with open-angle glaucoma. Can J Ophthalmol 50(2):127–131Google Scholar
  9. 9.
    Leleu I, Penaud B, Blumen-Ohana E et al (2018) Late and sustained intraocular pressure elevation related to intravitreal anti-VEGF injections: cases requiring filtering surgery (French translation of the article). J Fr Ophtalmol 41(9):789–801Google Scholar
  10. 10.
    Jalil A, Fenerty C, Charles S (2007) Intravitreal bevacizumab (Avastin) causing acute glaucoma: an unreported complication. Eye (Lond) 21(12):1541Google Scholar
  11. 11.
    Bakri SJ, McCannel CA, Edwards AO, Moshfeghi DM (2008) Persisent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol 246(7):955–958Google Scholar
  12. 12.
    Zhou Y, Zhou M, Xia S et al (2016) Sustained elevation of intraocular pressure associated with intravitreal administration of anti-vascular endothelial growth factor: a systematic review and meta-analysis. Sci Rep 6:39301Google Scholar
  13. 13.
    Kahook MY, Kimura AE, Wong LJ et al (2009) Sustained elevation in intraocular pressure associated with intravitreal bevacizumab injections. Ophthalmic Surg Lasers Imaging 40(3):293–295Google Scholar
  14. 14.
    Adelman RA, Zheng Q, Mayer HR (2010) Persistent ocular hypertension following intravitreal bevacizumab and ranibizumab injections. J Ocul Pharmacol Ther 26(1):105–110Google Scholar
  15. 15.
    Hoang QV, Tsuang AJ, Gelman R et al (2013) Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy. Retina 33(1):179–187Google Scholar
  16. 16.
    Bakri SJ, Moshfeghi DM, Francom S et al (2014) Intraocular pressure in eyes receiving monthly ranibizumab in 2 pivotal age-related macular degeneration clinical trials. Ophthalmology 121(5):1102–1108Google Scholar
  17. 17.
    Vo Kim S, Fajnkuchen F, Sarda V et al (2017) Sustained intraocular pressure elevation in eyes treated with intravitreal injections of anti-vascular endothelial growth factor for diabetic macular edema in a real-life setting. Graefes Arch Clin Exp Ophthalmol 255(11):2165–2171Google Scholar
  18. 18.
    Bressler SB, Almukhtar T, Bhorade A et al (2015) Repeated intravitreous ranibizumab injections for diabetic macular edema and the risk of sustained elevation of intraocular pressure or the need for ocular hypotensive treatment. JAMA Ophthalmol 133(5):589–597Google Scholar
  19. 19.
    Choi DY, Ortube MC, McCannel CA et al (2011) Sustained elevated intraocular pressures after intravitreal injection of bevacizumab, ranibizumab, and pegaptanib. Retina 31(6):1028–1035Google Scholar
  20. 20.
    Baek SU, Park IW, Suh W (2016) Long-term intraocular pressure changes after intravitreal injection of bevacizumab. Cutan Ocul Toxicol 35(4):310–314Google Scholar
  21. 21.
    Good TJ, Kimura AE, Mandava N, Kahook MY (2011) Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthalmol 95(8):1111–1114Google Scholar
  22. 22.
    Hoang QV, Mendonca LS, Della Torre KE et al (2012) Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections. Ophthalmology 119(2):321–326Google Scholar
  23. 23.
    Mathalone N, Arodi-Golan A, Sar S et al (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(10):1435–1440Google Scholar
  24. 24.
    Al-Abdullah AA, Nowilaty SR, Asghar N et al (2015) Intraocular pressure trends after intravitreal injections of anti-vascular endothelial growth factor agents for diabetic macular edema. Retina 35(3):440–448Google Scholar
  25. 25.
    Freund KB, Hoang QV, Saroj N, Thompson D (2015) Intraocular pressure in patients with neovascular age-related macular degeneration receiving intravitreal aflibercept or ranibizumab. Ophthalmology 122(9):1802–1810Google Scholar
  26. 26.
    Kim YJ, Sung KR, Lee KS et al (2014) Long-term effects of multiple intravitreal antivascular endothelial growth factor injections on intraocular pressure. Am J Ophthalmol 157(6):1266–71 e1Google Scholar
  27. 27.
    Nariani A, Williams B, Hariprasad SM (2016) Long-term effect of anti-vascular endothelial growth factor injections on intraocular pressure. Indian J Ophthalmol 64(9):643–647Google Scholar
  28. 28.
    Wehrli SJ, Tawse K, Levin MH et al (2012) A lack of delayed intraocular pressure elevation in patients treated with intravitreal injection of bevacizumab and ranibizumab. Retina 32(7):1295–1301Google Scholar
  29. 29.
    Boyer DS, Goldbaum M, Leys AM et al (2014) Effect of pegaptanib sodium 0.3 mg intravitreal injections (Macugen) in intraocular pressure: posthoc analysis from V.I.S.I.O.N. study. Br J Ophthalmol 98(11):1543–1546Google Scholar
  30. 30.
    Atchison EA, Wood KM, Mattox CG et al (2018) The real-world effect of intravitreous anti-vascular endothelial growth factor drugs on intraocular pressure: an analysis using the IRIS registryGoogle Scholar
  31. 31.
    Eadie BD, Etminan M, Carleton BC et al (2017) Association of repeated intravitreous bevacizumab injections with risk for glaucoma surgery. JAMA Ophthalmol 135(4):363–368Google Scholar
  32. 32.
    Yannuzzi NA, Patel SN, Bhavsar KV et al (2014) Predictors of sustained intraocular pressure elevation in eyes receiving intravitreal anti-vascular endothelial growth factor therapy. Am J Ophthalmol 158(2):319–27 e2Google Scholar
  33. 33.
    Beato J, Pedrosa AC, Pinheiro-Costa J et al (2016) Long-term effect of anti-VEGF agents on intraocular pressure in age-related macular degeneration. Ophthalmic Res 56(1):30–34Google Scholar
  34. 34.
    Pershing S, Bakri SJ, Moshfeghi DM (2013) Ocular hypertension and intraocular pressure asymmetry after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmic Surg Lasers Imaging Retina 44(5):460–464Google Scholar
  35. 35.
    Segal O, Ferencz JR, Cohen P et al (2013) Persistent elevation of intraocular pressure following intravitreal injection of bevacizumab. Isr Med Assoc J 15(7):352–355Google Scholar
  36. 36.
    Dedania VS, Bakri SJ (2015) Sustained elevation of intraocular pressure after intravitreal anti-VEGF agents: what is the evidence? Retina 35(5):841–858Google Scholar
  37. 37.
    Kahook MY, Ammar DA (2010) In vitro effects of antivascular endothelial growth factors on cultured human trabecular meshwork cells. J Glaucoma 19(7):437–441Google Scholar
  38. 38.
    Kahook MY, Liu L, Ruzycki P et al (2010) High-molecular-weight aggregates in repackaged bevacizumab. Retina 30(6):887–892Google Scholar
  39. 39.
    Apte RS, Gordon M, Kass MA (2017) Anti-VEGF injections and glaucoma surgery. JAMA Ophthalmol 135(4):368–369Google Scholar
  40. 40.
    Tseng JJ, Vance SK, Della Torre KE et al (2012) Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. J Glaucoma 21(4):241–247Google Scholar
  41. 41.
    Martinez-de-la-Casa JM, 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(10):6214–6218Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology, Scheie Eye InstituteUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  2. 2.Center for Preventative Ophthalmology and BiostatisticsUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  3. 3.Department of Biostatistics & Epidemiology, Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  4. 4.Leonard Davis InstituteUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA

Personalised recommendations