Retreatment by series of three intravitreal injections of ranibizumab in neovascular age-related macular degeneration: long-term outcomes

  • Maher Saleh
  • Mehdi Kheliouen
  • Eliza Tebeanu
  • Laurent Ballonzoli
  • Tristan Bourcier
  • Claude Speeg-Schatz
  • David Gaucher
Retinal Disorders

Abstract

Background

The purpose of this study was to analyze the results of a retreatment regimen using a series of three monthly intravitreal ranibizumab injections (IVR), instead of one injection, and to determine if this treatment scheme can safely reduce the number of injections and the number of visits compared to the widely used PrONTO study retreatment protocol.

Methods

>Sixty-six eyes of 60 patients with exudative age-related macular degeneration (AMD) were included. The mean follow-up period was 27 months (range, 11–48 months). The mean age of the patients was 79 years (range, 65–93 years). All patients received three initial IVRs, and were retreated with a new series of three monthly IVRs when needed. The retreatment criteria were: visual loss of ≥5 ETDRS letters and/or signs of retinal exudation on OCT, new macular hemorrhage, expansion of new vessels. Follow-up visits were conducted 1 month after the last IVR of each series, and renewed on a monthly basis when no retreatment was required. Each visit included a comprehensive ophthalmological examination with BCVA measurement and OCT examination.

Results

Mean VA did not improve during follow-up (53.18 letters at the initial visit versus 54.18 at the last visit, p > 0.05). However, VA stabilized or improved in 66.6 % of the eyes. A gain of ≥15 letters was observed in 28.8 % of eyes. On average, over 2 years, the number of IVRs was five per year, and the number of follow-up visits was four per year.

Conclusion

Even if no gain in VA is observed after 2 years, this treatment regimen reduces the number of IVRs and control visits. The proportion of patients with a VA gain of three lines or more was smaller than the one reported in the original PrONTO study, but higher than the rates reported in other studies implementing the PrONTO recommendations in everyday practice. The benefit of the three IVR retreatment scheme should be prospectively studied and compared to the PRN regimen.

Keywords

Age-related macular degeneration Intravitreal injections Ranibizumab Retreatment protocol 

References

  1. 1.
    Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP (2004) Global data on visual impairment in the year 2002. Bull World Health Organ 82:844–851PubMedGoogle Scholar
  2. 2.
    Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR (2012) The estimated prevalence and incidence of late-stage age-related macular degeneration in the UK. Br J Ophthalmol 96:752–756PubMedCrossRefGoogle Scholar
  3. 3.
    Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431PubMedCrossRefGoogle Scholar
  4. 4.
    Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444PubMedCrossRefGoogle Scholar
  5. 5.
    Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T (2009) Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology 116:57–65PubMedCrossRefGoogle Scholar
  6. 6.
    Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364:1897–1908PubMedCrossRefGoogle Scholar
  7. 7.
    Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL 3rd (2012) Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 119:1388–1398PubMedCrossRefGoogle Scholar
  8. 8.
    Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW Jr, Esquiabro M (2007) An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 143:566–583PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen SY, Dubois L, Tadayoni R, Fajnkuchen F, Nghiem-Buffet S, Delahaye-Mazza C, Guiberteau B, Quentel G (2009) Results of one-year’s treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting. Am J Ophthalmol 148:409–413PubMedCrossRefGoogle Scholar
  10. 10.
    Bloch SB, la Cour M, Sander B, Hansen LK, Fuchs J, Lund-Andersen H, Larsen M (2011) Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment. Acta Ophthalmol. doi:10.1111/j.1755-3768.2011.02268.x
  11. 11.
    Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Wordsworth S, Reeves BC (2012) Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN Randomized Trial. Ophthalmology 119:1399–1411PubMedCrossRefGoogle Scholar
  12. 12.
    Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N (2008) Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol 145:239–248PubMedCrossRefGoogle Scholar
  13. 13.
    Schmidt-Erfurth U, Eldem B, Guymer R, Korobelnik JF, Schlingemann RO, Axer-Siegel R, Wiedemann P, Simader C, Gekkieva M, Weichselberger A (2011) Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology 118:831–839PubMedCrossRefGoogle Scholar
  14. 14.
    Lalwani GA, Rosenfeld PJ, Fung AE, Dubovy SR, Michels S, Feuer W, Davis JL, Flynn HW Jr, Esquiabro M (2009) A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol 148:43–58PubMedCrossRefGoogle Scholar
  15. 15.
    Querques G, Azrya S, Martinelli D, Berboucha E, Feldman A, Pece A, Coscas G, Soubrane G, Souied EH (2010) Ranibizumab for exudative age-related macular degeneration: 24-month outcomes from a single-centre institutional setting. Br J Ophthalmol 94:292–296PubMedCrossRefGoogle Scholar
  16. 16.
    Arias L, Armada F, Donate J, Garcia-Arumi J, Giralt J, Pazos B, Pinero A, Martinez F, Mondejar JJ, Ortega I, Zlateva G, Buggage R (2009) Delay in treating age-related macular degeneration in Spain is associated with progressive vision loss. Eye (Lond) 23:326–333CrossRefGoogle Scholar
  17. 17.
    Muether PS, Hermann MM, Koch K, Fauser S (2011) Delay between medical indication to anti-VEGF treatment in age-related macular degeneration can result in a loss of visual acuity. Graefes Arch Clin Exp Ophthalmol 249:633–637PubMedCrossRefGoogle Scholar
  18. 18.
    Dadgostar H, Ventura AA, Chung JY, Sharma S, Kaiser PK (2009) Evaluation of injection frequency and visual acuity outcomes for ranibizumab monotherapy in exudative age-related macular degeneration. Ophthalmology 116:1740–1747PubMedCrossRefGoogle Scholar
  19. 19.
    Heimes B, Lommatzsch A, Zeimer M, Gutfleisch M, Spital G, Dietzel M, Pauleikhoff D (2011) Long-term visual course after anti-VEGF therapy for exudative AMD in clinical practice evaluation of the German reinjection scheme. Graefes Arch Clin Exp Ophthalmol 249:639–644PubMedCrossRefGoogle Scholar
  20. 20.
    Dunavoelgyi R, Sacu S, Eibenberger K, Palkovits S, Leydolt C, Pruente C, Schmidt-Erfurth U (2012) Retreatment with anti-vascular endothelial growth factor therapy based on changes in visual acuity after initial stabilization of neovascular age-related macular degeneration: 3-year follow-up results. Retina 12:2223–2227Google Scholar
  21. 21.
    Oubraham H, Cohen SY, Samimi S, Marotte D, Bouzaher I, Bonicel P, Fajnkuchen F, Tadayoni R (2011) Inject and extend dosing versus dosing as needed: a comparative retrospective study of ranibizumab in exudative age-related macular degeneration. Retina 31:26–30PubMedCrossRefGoogle Scholar
  22. 22.
    Rosenfeld PJ, Shapiro H, Tuomi L, Webster M, Elledge J, Blodi B (2011) Characteristics of patients losing vision after 2 years of monthly dosing in the phase III ranibizumab clinical trials. Ophthalmology 118:523–530PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Maher Saleh
    • 1
  • Mehdi Kheliouen
    • 2
  • Eliza Tebeanu
    • 2
  • Laurent Ballonzoli
    • 2
  • Tristan Bourcier
    • 2
    • 3
  • Claude Speeg-Schatz
    • 2
  • David Gaucher
    • 2
    • 3
    • 4
  1. 1.Department of OphthalmologyUniversity Hospital Jean Minjoz of Besançon, Franche-Comté UniversityBesançonFrance
  2. 2.Department of Ophthalmology, Nouvel Hôpital CivilUniversity Hospital of Strasbourg, Strasbourg UniversityStrasbourgFrance
  3. 3.Institut de Bactériologie, Unité: EA-7290 Virulence bactérienne précoce, Fédération de Médecine Translationnelle de Strasbourg (FMTS)Université de StrasbourgStrasbourgFrance
  4. 4.Department of Ophthalmology, Nouvel Hôpital CivilUniversity Hospital of Strasbourg, Strasbourg UniversityStrasbourg CEDEXFrance

Personalised recommendations