Prospective study evaluating the predictability of need for retreatment with intravitreal ranibizumab for age-related macular degeneration

  • Irmela Mantel
  • Angeliki Deli
  • Katia Iglesias
  • Aude Ambresin
Retinal Disorders

Abstract

Purpose

To investigate the rhythm and predictability of the need for retreatment with intravitreal injections of ranibizumab for neovascular age-related macular degeneration (nAMD).

Methods

This prospective study enrolled 39 patients with treatment-naïve nAMD. After three loading doses of intravitreal ranibizumab, patients underwent an intensified follow-up for 12 months (initially weekly, then with stepwise increases to every 2 weeks and to monthly after each injection). Patients were retreated on an as-needed basis if any fluid or increased central retinal thickness (CRT) (>50μm) was found on spectral domain optical coherence tomography (OCT). Statistical analysis included patients who received at least two retreatments (five injections).

Results

A mean of 7.5 injections (range 0–12) were given between months 3 and 15. The mean visual acuity increased by 13.1 and 12.6 ETDRS letters at months 12 and 15 respectively. Two or more injection–retreatment intervals were found in 31 patients. The variability of their intra-individual intervals up to 14 weeks was small (SD 0–2.13 weeks), revealing a high regularity of the retreatment rhythm. The SD was correlated with the mean interval duration (r = 0.89, p < 0.001). The first interval was a good predictor of the following intervals (regression coefficient =0.81). One retreatment criterion was stable in 97 % of patients (cysts or subretinal fluid).

Conclusion

The results of this study demonstrate a high intra-individual predictability of retreatment need with ranibizumab injections for nAMD. These findings may be helpful for developing individualized treatment plans for maintained suppression of disease activity with a minimum of injections and visits.

Keywords

Neovascular age-related macular degeneration Ranibizumab Intravitreal injection P.R.N. treatment regimen Predictability Optical coherence tomography 

References

  1. 1.
    Bressler NM (2004) Age-related macular degeneration is the leading cause of blindness. JAMA 291:1900–1901PubMedCrossRefGoogle Scholar
  2. 2.
    Friedman DS, O’Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572PubMedCrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    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
  5. 5.
    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
  6. 6.
    Abraham P, Yue H, Wilson L (2010) Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2. Am J Ophthalmol 150:315–324PubMedCrossRefGoogle Scholar
  7. 7.
    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
  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.
    Mantel I, Zografos L, Ambresin A (2008) Early clinical experience with ranibizumab for occult and minimally classic neovascular membranes in age-related macular degeneration. Ophthalmologica 222:321–323PubMedCrossRefGoogle Scholar
  10. 10.
    Engelbert M, Zweifel SA, Freund KB (2010) Long-term follow-up for type 1 (subretinal pigment epithelium) neovascularization using a modified "treat and extend" dosing regimen of intravitreal antivascular endothelial growth factor therapy. Retina 30:1368–1375PubMedCrossRefGoogle Scholar
  11. 11.
    Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD (2010) A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology 117:2134–2140PubMedCrossRefGoogle Scholar
  12. 12.
    Horster R, Ristau T, Sadda SR, Liakopoulos S (2011) Individual recurrence intervals after anti-VEGF therapy for age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 249:645–652PubMedCrossRefGoogle Scholar
  13. 13.
    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
  14. 14.
    Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V (2005) Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci 46:726–733PubMedCrossRefGoogle Scholar
  15. 15.
    Mordenti J, Cuthbertson RA, Ferrara N, Thomsen K, Berleau L, Licko V, Allen PC, Valverde CR, Meng YG, Fei DT, Fourre KM, Ryan AM (1999) Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol 27:536–544PubMedCrossRefGoogle Scholar
  16. 16.
    Blick SK, Keating GM, Wagstaff AJ (2007) Ranibizumab. Drugs 67:1199–1206PubMedCrossRefGoogle Scholar
  17. 17.
    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
  18. 18.
    Gerding H, Loukopoulos V, Riese J, Hefner L, Timmermann M (2011) Results of flexible ranibizumab treatment in age-related macular degeneration and search for parameters with impact on outcome. Graefes Arch Clin Exp Ophthalmol 249:653–662PubMedCrossRefGoogle Scholar
  19. 19.
    Holz FG, Meyer C, Eter N, on behalf of the SUSTAIN study group (2009) Safety and efficacy of ranibizumab treatment in patients with neovascular age-related macular degeneration: 12-Month results of the SUSTAIN study. Invest Ophthalmol Vis Sci 50: E-Abstract 3095Google Scholar
  20. 20.
    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
  21. 21.
    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

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Irmela Mantel
    • 1
    • 3
  • Angeliki Deli
    • 1
  • Katia Iglesias
    • 2
  • Aude Ambresin
    • 1
  1. 1.Ophthalmology Department of the University of LausanneJules-Gonin Eye HospitalLausanneSwitzerland
  2. 2.Centre for Clinical EpidemiologyUniversity Hospital LausanneLausanneSwitzerland
  3. 3.University Eye Hospital Jules GoninLausanne 7Switzerland

Personalised recommendations