Skip to main content

Advertisement

SpringerLink
Log in

Intravitreal bevacizumab treatment for neovascular glaucoma: histopathological analysis of trabeculectomy specimens

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

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Background

Neovascular glaucoma (NVG) is a serious complication for patients with proliferative diabetic retinopathy (PDR). Bevacizumab is a full-length humanized monoclonal antibody that binds all isoforms of vascular endothelial growth factor (VEGF). Recently, encouraging results regarding the off-label use of intravitreal bevacizumab (IVB) for the treatment of NVG have been reported. We evaluated the histology of bevacizumab-treated trabeculectomy specimens to clarify IVB’s biological effects on angle neovascularization.

Methods

We retrospectively reviewed the charts of a consecutive series of 15 eyes of 13 patients who underwent trabeculectomy to treat NVG caused by PDR. In ten eyes of eight patients, 1.25 mg bevacizumab was injected intravitreally via the pars plana. Using light or electron microscopy, the surgically excised trabecular tissue was compared to that without IVB.

Results

Light microscopy revealed decreased edema, fibrin deposition, inflammation and vascular congestion in the trabecular meshwork in specimens with IVB compared to those without IVB. Electron microscopy revealed endothelial cell degeneration in the bevacizumab-treated specimens.

Conclusions

The biological effects on angle neovascularization after IVB may involve reduced vascular permeability, decreased inflammatory reaction, loss of vascular function, and endothelial cell degeneration.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    Article  PubMed  CAS  Google Scholar 

  2. Tripathi RC, Li J, Tripathi BJ, Chalam KV, Adamis AP (1998) Increased level of vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma. Ophthalmology 105:232–237

    Article  PubMed  CAS  Google Scholar 

  3. Fernandez-Vigo J, Castro J, Macarro A (1997) Diabetic iris neovascularization. Natural history and treatment. Acta Ophthalmol Scand 75:89–93

    Article  PubMed  CAS  Google Scholar 

  4. Hurwitz HI, Fehrenbacher L, Hainsworth JD, Heim W, Berlin J, Holmgren E, Hambleton J, Novotny WF, Kabbinavar F (2005) Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23:3502–3508

    Article  PubMed  CAS  Google Scholar 

  5. Rosenfeld PJ, Fung AE, Puliafito CA (2005) Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 36:336–339

    PubMed  Google Scholar 

  6. Rosenfeld PJ, Moshfeghi AA, Puliafito CA (2005) Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 36:331–335

    PubMed  Google Scholar 

  7. Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ (2006) Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 113:363–372

    Article  PubMed  Google Scholar 

  8. Avery RL (2006) Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina 26:352–354

    Article  PubMed  Google Scholar 

  9. Davidorf FH, Mouser JG, Derick RJ (2006) Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina 26:354–356

    Article  PubMed  Google Scholar 

  10. Oshima Y, Sakaguchi H, Gomi F, Tano Y (2006) Regression of iris neovascularization after intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy. Am J Ophthalmol 142:155–158

    Article  PubMed  CAS  Google Scholar 

  11. Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf S, Sarra GM (2006) Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am J Ophthalmol 142:1054–1056

    Article  PubMed  CAS  Google Scholar 

  12. Silva PJ, Jorge R, Alves CR, Rodrigues ML, Scott IU (2006) Short-term results of intravitreal bevacizumab (Avastin) on anterior segment neovascularization in neovascular glaucoma. Acta Ophthalmol Scan 84:556–557

    Article  Google Scholar 

  13. Wakabayashi T, Oshima Y, Sakaguchi H, Ikuno Y, Miki A, Gomi F, Otori Y, Kamei M, Kusaka S, Tano Y (2008) Intravitreal bevacizumab to treat iris neovascularization and neovascular glaucoma secondary to ischemic retinal diseases in 41 consecutive cases. Ophthalmology 115:1571–1580

    Article  PubMed  Google Scholar 

  14. Kubota T, Tawara A, Hata Y, Khalil A, Inomata H (1996) Neovascular tissue in the intertrabecular spaces in eyes with neovascular glaucoma. Br J Ophthalmol 80:750–754

    Article  PubMed  CAS  Google Scholar 

  15. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    Article  PubMed  CAS  Google Scholar 

  16. Alon T, Hemo I, Itin A, Pe'er J, Stone J, Keshet E (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024–1028

    Article  PubMed  CAS  Google Scholar 

  17. Zachary I, Gliki G (2001) Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res 49:568–581

    Article  PubMed  CAS  Google Scholar 

  18. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039

    PubMed  CAS  Google Scholar 

  19. Kohno R, Hata Y, Mochizuki Y, Arita R, Kawahara S, Kita T, Miyazaki M, Hisatomi T, Ikeda Y, Aiello LP, Ishibashi T (2010) Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection. Am J Ophthalmol 150:223–229

    Article  PubMed  CAS  Google Scholar 

  20. Kubota T, Aoki R, Harada Y, Tou N, Kohno Y, Tawara A, Satoh H, Shimajiri S (2009) Trabecular meshwork in neovascular glaucoma eyes after the intravitreal injection of bevacizumab. Br J Ophthalmol 93:557–558

    Article  PubMed  CAS  Google Scholar 

  21. Kim I, Moon SO, Kim SH, Kim HJ, Koh YS, Koh GY (2001) Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells. J Biol Chem 276:7614–7620

    Article  PubMed  CAS  Google Scholar 

  22. Reinders ME, Sho M, Izawa A, Wang P, Mukhopadhyay D, Koss KE, Geehan CS, Luster AD, Sayegh MH, Briscoe DM (2003) Proinflammatory functions of vascular endothelial growth factor in alloimmunity. J Clin Invest 112:1655–1665

    PubMed  CAS  Google Scholar 

  23. Gibran SK, Sachdev A, Stappler T, Newsome R, Wong D, Hiscott P (2007) Histological findings of a choroidal neovascular membrane removed at the time of macular translocation in a patient previously treated with intravitreal bevacizumab treatment (Avastin). Br J Ophthalmol 91:602–604

    Article  PubMed  CAS  Google Scholar 

  24. Lassota N, Prause JU, Scherfig E, Kiilgaard JF, la Cour M (2010) Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization. Acta Ophthalmol 88:300–308

    PubMed  CAS  Google Scholar 

  25. Sugimoto Y, Mochizuki H, Okumichi H, Takumida M, Takamatsu M, Kawamata S, Kiuchi Y (2010) Effect of intravitreal bevacizumab on iris vessels in neovascular glaucoma patients. Graefes Arch Clin Exp Ophthalmol 248:1601–1609

    Article  PubMed  CAS  Google Scholar 

  26. Saito Y, Higashide T, Takeda H, Ohkubo S, Sugiyama K (2010) Beneficial effects of preoperative intravitreal bevacizumab on trabeculectomy outcomes in neovascular glaucoma. Acta Ophthalmol 88:96–102

    Article  PubMed  CAS  Google Scholar 

  27. Takihara Y, Inatani M, Kawaji T, Fukushima M, Iwao K, Iwao M, Tanihara H (2011) Combined intravitreal bevacizumab and trabeculectomy with mitomycin C versus trabeculectomy with mitomycin C alone for neovascular glaucoma. J Glaucoma 20:196–201

    Article  PubMed  Google Scholar 

  28. Julien S, Heiduschka P, Hofmeister S, Schraermeyer U (2008) Immunohistochemical localisation of intravitreally injected bevacizumab at the posterior pole of the primate eye: implication for the treatment of retinal vein occlusion. Br J Ophthalmol 92:1424–1428

    Article  PubMed  CAS  Google Scholar 

  29. Heiduschka P, Fietz H, Hofmeister S, Schultheiss S, Mack AF, Peters S, Ziemssen F, Niggemann B, Julien S, Bartz-Schmidt KU, Schraermeyer U, Tübingen Bevacizumab Study Group (2007) Penetration of bevacizumab through the retina after intravitreal injection in the monkey. Invest Ophthalmol Vis Sci 48:2814–2823

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Y. Morikawa and M. Imamura for assistance with the experiments. KN International provided language assistance. This work was supported in part by a Grant-in-Aid (to YI) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (#20791259).

Financial relationship

None.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Noriko Yoshida, Toshio Hisatomi, Yasuhiro Ikeda, Ri-ichiro Kohno, Yusuke Murakami, Hiroyuki Imaki, Kimihiko Fujisawa & Tatsuro Ishibashi

  2. Ohshima Hospital of Ophthalmology, 11-8 Kamigofuku, Hakata-ku, Fukuoka, 812-0036, Japan

    Akifumi Ueno

Authors
  1. Noriko Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshio Hisatomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasuhiro Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ri-ichiro Kohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yusuke Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroyuki Imaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akifumi Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kimihiko Fujisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tatsuro Ishibashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiro Ikeda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoshida, N., Hisatomi, T., Ikeda, Y. et al. Intravitreal bevacizumab treatment for neovascular glaucoma: histopathological analysis of trabeculectomy specimens. Graefes Arch Clin Exp Ophthalmol 249, 1547–1552 (2011). https://doi.org/10.1007/s00417-011-1761-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-011-1761-2

Keywords

Search

Navigation