Skip to main content

Advertisement

SpringerLink
Log in

Intravitreal bevacizumab for neovascular glaucoma in uveal melanoma treated by proton beam therapy

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

Abstract

Background

To evaluate the efficacy of bevacizumab on reduction of the enucleation rate and control of intraocular pressure (IOP) in neovascular glaucoma (NVG)-complicating proton beam therapy for UM and to identify the determinants of the efficacy of bevacizumab.

Methods

Retrospective comparative study of patients with rubeosis following proton therapy for uveal melanoma. Patients were divided into two groups: a bevacizumab group and a control group which comprised two subgroups: panretinal photocoagulation (PRP)/cryotherapy and observation subgroups. Bevacizumab was administered by three intravitreal injections at 1-month intervals. A second series of injections was administered when necessary. Data concerning IOP and the secondary enucleation rate were collected and compared between the two groups. Univariate and multivariate analyses were performed to determine predictive factors of response to bevacizumab.

Results

A total of 169 patients who developed rubeosis following proton therapy between 2006 and 2016 were included: 44 patients in the bevacizumab group and 125 in the control group (38 in the PRP/cryotherapy subgroup and 87 in the observation subgroup). The two groups presented the same baseline characteristics apart from hypertension, retro-equatorial site, and proximity of the optic disk, which were more frequent in the control group, while initial retinal detachment and larger tumor volume were more frequent in the bevacizumab group. After a mean follow-up of 31 months, IOP was less than 21 mmHg in 54.54% of patients after IVB versus 72.7% before treatment (p = 0.06). Statistical analysis did not reveal any statistically significant reduction of the enucleation rate in the bevacizumab group compared to the observational group, whereas the PRP/cryotherapy group showed better eye retention rate (p = 0.15). No enucleation was performed when IOP was < 21 mmHg before IVB. Multivariate analysis identified initial IOP < 21 mmHg and UM situated away from the macula as predictive factors of good response to bevacizumab.

Conclusion

Despite the improvement of IOP level, intravitreal bevacizumab (IVB) did not reduce the overall enucleation rate in NVG following proton beam therapy. Nevertheless, this treatment was effective in the early phases of NVG or as preventive treatment. PRP remains a valid treatment for NVG.

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
Fig. 3

Similar content being viewed by others

References

  1. Damato B (2012) Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye (Lond) 26:1157–1172. https://doi.org/10.1038/eye.2012.126

    Article  CAS  Google Scholar 

  2. Hawkins BS (2011) Collaborative ocular melanoma study randomized trial of I-125 brachytherapy. Clin Trials 8:661–673. https://doi.org/10.1177/1740774511419684

    Article  PubMed  Google Scholar 

  3. Desjardins L, Lumbroso-Le Rouic L, Levy-Gabriel C et al (2012) Treatment of uveal melanoma by accelerated proton beam. Dev Ophthalmol 49:41–57. https://doi.org/10.1159/000328257

    Article  PubMed  Google Scholar 

  4. Groenewald C, Konstantinidis L, Damato B (2013) Effects of radiotherapy on uveal melanomas and adjacent tissues. Eye (Lond) 27:163–171. https://doi.org/10.1038/eye.2012.249

    Article  CAS  Google Scholar 

  5. Damato B, Kacperek A, Chopra M et al (2005) Proton beam radiotherapy of choroidal melanoma: the Liverpool-Clatterbridge experience. Int J Radiat Oncol Biol Phys 62:1405–1411. https://doi.org/10.1016/j.ijrobp.2005.01.016

    Article  PubMed  Google Scholar 

  6. Egger E, Zografos L, Schalenbourg A et al (2003) Eye retention after proton beam radiotherapy for uveal melanoma. Int J Radiat Oncol Biol Phys 55:867–880

    Article  PubMed  Google Scholar 

  7. Seibel I, Riechardt AI, Heufelder J et al (2017) Adjuvant ab interno tumor treatment after proton beam irradiation. Am J Ophthalmol. https://doi.org/10.1016/j.ajo.2017.03.027

  8. Dendale R, Lumbroso-Le Rouic L, Noel G et al (2006) Proton beam radiotherapy for uveal melanoma: results of Curie Institut-Orsay proton therapy center (ICPO). Int J Radiat Oncol Biol Phys 65:780–787. https://doi.org/10.1016/j.ijrobp.2006.01.020

    Article  PubMed  Google Scholar 

  9. Conway RM, Poothullil AM, Daftari IK et al (2006) Estimates of ocular and visual retention following treatment of extra-large uveal melanomas by proton beam radiotherapy. Arch Ophthalmol 124:838–843. https://doi.org/10.1001/archopht.124.6.838

    Article  PubMed  Google Scholar 

  10. Foss A, Whelehan I, Hungerford J et al (1997) Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma. Br J Ophthalmol 81:748–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mishra KK, Daftari IK, Weinberg V et al (2013) Risk factors for neovascular glaucoma after proton beam therapy of uveal melanoma: a detailed analysis of tumor and dose-volume parameters. Int J Radiat Oncol Biol Phys 87:330–336. https://doi.org/10.1016/j.ijrobp.2013.05.051

    Article  PubMed  Google Scholar 

  12. Aref AA (2016) Current management of glaucoma and vascular occlusive disease. Curr Opin Ophthalmol 27:140–145. https://doi.org/10.1097/ICU.0000000000000239

    Article  PubMed  Google Scholar 

  13. Reichstein D (2015) Current treatments and preventive strategies for radiation retinopathy. Curr Opin Ophthalmol 26:157–166. https://doi.org/10.1097/ICU.0000000000000141

    Article  PubMed  Google Scholar 

  14. Archer DB, Amoaku WM, Gardiner TA (1991) Radiation retinopathy--clinical, histopathological, ultrastructural and experimental correlations. Eye (Lond) 5(Pt 2):239–251. https://doi.org/10.1038/eye.1991.39

    Article  Google Scholar 

  15. Konstantinidis L, Groenewald C, Coupland SE, Damato B (2014) Trans-scleral local resection of toxic choroidal melanoma after proton beam radiotherapy. Br J Ophthalmol 98:775–779. https://doi.org/10.1136/bjophthalmol-2013-304501

    Article  PubMed  Google Scholar 

  16. Ly LV, Bronkhorst IHG, van Beelen E et al (2010) Inflammatory cytokines in eyes with uveal melanoma and relation with macrophage infiltration. Invest Ophthalmol Vis Sci 51:5445–5451. https://doi.org/10.1167/iovs.10-5526

    Article  PubMed  PubMed Central  Google Scholar 

  17. Boyd SR, Tan D, Bunce C et al (2002) Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouring uveal melanoma: identification of a potential therapeutic window. Br J Ophthalmol 86:448–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Missotten GSO, Notting IC, Schlingemann RO et al (2006) Vascular endothelial growth factor a in eyes with uveal melanoma. Arch Ophthalmol 124:1428–1434. https://doi.org/10.1001/archopht.124.10.1428

    Article  CAS  PubMed  Google Scholar 

  19. Yang M, Kuang X, Pan Y et al (2014) Clinicopathological characteristics of vascular endothelial growth factor expression in uveal melanoma: a meta-analysis. Mol Clin Oncol 2:363–368. https://doi.org/10.3892/mco.2014.247

    Article  PubMed  PubMed Central  Google Scholar 

  20. Boyd SR, Gittos A, Richter M et al (2006) Proton beam therapy and iris neovascularisation in uveal melanoma. Eye (Lond) 20:832–836. https://doi.org/10.1038/sj.eye.6702072

    Article  CAS  Google Scholar 

  21. Lima BR, Schoenfield LR, Singh AD (2011) The impact of intravitreal bevacizumab therapy on choroidal melanoma. Am J Ophthalmol 151:323.e2–328.e2. https://doi.org/10.1016/j.ajo.2010.08.040

    Article  Google Scholar 

  22. el Filali M, Ly LV, Luyten GPM et al (2012) Bevacizumab and intraocular tumors: an intriguing paradox. Mol Vis 18:2454–2467

    PubMed  PubMed Central  Google Scholar 

  23. Shah SU, Shields CL, Bianciotto CG et al (2014) Intravitreal bevacizumab at 4-month intervals for prevention of macular edema after plaque radiotherapy of uveal melanoma. Ophthalmology 121:269–275. https://doi.org/10.1016/j.ophtha.2013.08.039

    Article  PubMed  Google Scholar 

  24. Andrés-Guerrero V, Perucho-González L, García-Feijoo J et al (2017) Current perspectives on the use of anti-VEGF drugs as adjuvant therapy in glaucoma. Adv Ther 34:378–395. https://doi.org/10.1007/s12325-016-0461-z

    Article  PubMed  Google Scholar 

  25. Vásquez LM, Somani S, Altomare F, Simpson ER (2009) Intracameral bevacizumab in the treatment of neovascular glaucoma and exudative retinal detachment after brachytherapy in choroidal melanoma. Can J Ophthalmol 44:106–107. https://doi.org/10.3129/i08-171

    Article  PubMed  Google Scholar 

  26. Yeung SN, Paton KE, Waite C, Maberley DA (2010) Intravitreal bevacizumab for iris neovascularization following proton beam irradiation for choroidal melanoma. Can J Ophthalmol 45:269–273. https://doi.org/10.3129/i09-259

    Article  PubMed  Google Scholar 

  27. Caujolle JP, Maschi C, Freton A et al (2012) Treatment of neovascular glaucoma after proton therapy for uveal melanomas with ranibizumab injection: preliminary results. Ophthalmic Res 47:57–60

    Article  CAS  PubMed  Google Scholar 

  28. Riechardt AI, Cordini D, Rehak M et al (2016) Trabeculectomy in patients with uveal melanoma after proton beam therapy. Graefes Arch Clin Exp Ophthalmol 254:1379–1385. https://doi.org/10.1007/s00417-016-3310-5

    Article  PubMed  Google Scholar 

  29. Kinyoun JL, Lawrence BS (1960) Barlow WE (1996) proliferative radiation retinopathy. Arch Ophthalmol 114:1097–1100

    Article  Google Scholar 

  30. Bianciotto C, Shields CL, Pirondini C et al (2010) Proliferative radiation retinopathy after plaque radiotherapy for uveal melanoma. Ophthalmology 117:1005–1012. https://doi.org/10.1016/j.ophtha.2009.10.015

    Article  PubMed  Google Scholar 

  31. Char DH, Bove R, Phillips TL (2003) Laser and proton radiation to reduce uveal melanoma-associated exudative retinal detachments. Am J Ophthalmol 136:180–182

    Article  PubMed  Google Scholar 

  32. Desjardins L, Lumbroso-Le Rouic L, Levy-Gabriel C et al (2006) Combined proton beam radiotherapy and transpupillary thermotherapy for large uveal melanomas: a randomized study of 151 patients. Ophthalmic Res 38:255–260. https://doi.org/10.1159/000094834

    Article  CAS  PubMed  Google Scholar 

  33. Cassoux N, Cayette S, Plancher C et al (2013) Choroidal melanoma: does endoresection prevent neovascular glaucoma in patient treated with proton beam irradiation? Retina 33:1441–1447. https://doi.org/10.1097/IAE.0b013e31827f65c8

    Article  PubMed  Google Scholar 

  34. Gibran SK, Kapoor KG (2009) Management of exudative retinal detachment in choroidal melanoma. Clin Experiment Ophthalmol 37:654–659. https://doi.org/10.1111/j.1442-9071.2009.02127.x

    Article  PubMed  Google Scholar 

  35. Newman H, Finger PT, Chin KJ, Pavlick AC (2011) Systemic bevacizumab (Avastin) for exudative retinal detachment secondary to choroidal melanoma. Eur J Ophthalmol 21:796–801. https://doi.org/10.5301/EJO.2011.6477

    Article  PubMed  Google Scholar 

  36. Parrozzani R, Pilotto E, Dario A et al (2013) Intravitreal triamcinolone versus intravitreal bevacizumab in the treatment of exudative retinal detachment secondary to posterior uveal melanoma. Am J Ophthalmol 155:127–133.e2. https://doi.org/10.1016/j.ajo.2012.06.026

    Article  CAS  PubMed  Google Scholar 

  37. Mantel I, Schalenbourg A, Bergin C et al (2014) Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma. Am J Ophthalmol 158:693.e2–701.e2. https://doi.org/10.1016/j.ajo.2014.07.002

    Article  Google Scholar 

Download references

Funding

No funding was received for this research.

Author information

Authors and Affiliations

  1. Ophthalmology Department, Institut Curie, Paris, France

    Amir Mahdjoubi, Stéphanie Lemaitre, Christine Levy, Livia Lumbroso-Le Rouic, Laurence Desjardins & Nathalie Cassoux

  2. Statistics Department, Institut Curie, Paris, France

    Marie Najean & Sylvain Dureau

  3. Radiation Oncology Department, Institut Curie, Paris, France

    Rémi Dendale

Authors
  1. Amir Mahdjoubi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie Najean
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stéphanie Lemaitre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sylvain Dureau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rémi Dendale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christine Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Livia Lumbroso-Le Rouic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Laurence Desjardins
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nathalie Cassoux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amir Mahdjoubi.

Ethics declarations

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its subsequent amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahdjoubi, A., Najean, M., Lemaitre, S. et al. Intravitreal bevacizumab for neovascular glaucoma in uveal melanoma treated by proton beam therapy. Graefes Arch Clin Exp Ophthalmol 256, 411–420 (2018). https://doi.org/10.1007/s00417-017-3834-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-017-3834-3

Keywords

Search

Navigation