Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 5/2011

01-05-2011 | Retinal Disorders

Results of flexible ranibizumab treatment in age-related macular degeneration and search for parameters with impact on outcome

Authors: Heinrich Gerding, Vlassios Loukopoulos, Juliane Riese, Lars Hefner, Melanie Timmermann

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 5/2011

Login to get access

Abstract

Background

The aim of this study was to analyse functional results of flexible ranibizumab treatment in exudative age-related macular degeneration (AMD), and to search for parameters with impact on outcome.

Methods

Analysis of a retrospective institutional case series (104 eyes) with a low-threshold re-treatment algorithm and monthly follow-up for 12 months.

Results

Visual acuity (VA) improved at month 3 by +6.7 letters and declined slightly until month 12 to a level of +5.0 letters. On average, eyes received 5.8 injections. A significant loss in VA occurred in the whole group between months 5 and 6 (−2.0 letters), never in the “winner” group (improvement of >5 letters at month 12), between months 5 and 6 (−3.8 letters) in the “stabilizer” group (∆ of ±5 letters at month 12) and twice, between months 3 and 7 (−7.0 letters) and months 9 and 12 (−6.9 letters), in the “loser” group (loss of >5 letters at month 12). These major functional declines followed moderate but significant increases in average CFT (OCT-central foveal thickness) of 23 to 33 μm. Increased CFT followed periods with a low percentage of treated eyes per month in each group. The amount of regained vision was significantly related to the extent of previous functional loss. The critical limit of short-term VA decline that was associated with the possibility for full VA restoration can approximately be quantified at −4 letters. Restoration of short-term VA deterioration (last month) was significantly better than long-term VA loss (related to the end of loading phase). Restoration of VA loss stratifies mainly into two groups: a group that regained −25 to 25% and one that regained 75 to 125%. A significant correlation was found between the number of injections and functional outcome at month 12 for eyes receiving more than four injections. It was calculated that a mean of 8.4 injections per eye would have been necessary to stabilize vision within the first 12 months.

Conclusions

CFT is a sensitive and early predictor of VA deterioration. Four letters of acute VA loss seems to be a critical limit. VA loss of ≥4 letters appears to be associated with incomplete recovery. Eyes with <1 line of gain at the end of the loading phase should be considered for continuation of treatment at months 3 and 4. According to our calculations an average number of 8.4 injections/eye seems to be necessary to maintain stabilization of vision in the first year of treatment.
Literature
1.
go back to reference Bressler NM (2004) Age-related macular degeneration is the leading cause of blindness. JAMA 291:1900–1901PubMedCrossRef Bressler NM (2004) Age-related macular degeneration is the leading cause of blindness. JAMA 291:1900–1901PubMedCrossRef
2.
go back to reference Wong T, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrenbach K, Probst C, Sledge I (2008) The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 115:116–126PubMedCrossRef Wong T, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrenbach K, Probst C, Sledge I (2008) The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 115:116–126PubMedCrossRef
3.
go back to reference Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S, ANCHOR Study Group (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444CrossRef Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S, ANCHOR Study Group (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444CrossRef
4.
go back to reference Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY, MARINA Study Group (2006) Ranibizumab for neovascular age related macular degeneration. N Engl J Med 355:1419–1431CrossRef Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY, MARINA Study Group (2006) Ranibizumab for neovascular age related macular degeneration. N Engl J Med 355:1419–1431CrossRef
7.
go back to reference Holz FG, Korobelnik JF, Lanzetta P, Mitchell P, Schmidt-Erfurth U, Wolf S, Markabi S, Schmidli H, Weichselberger A (2010) The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: Outcomes of a drug and disease model. Invest Ophthalmol Vis Sci 51:405–412PubMedCrossRef Holz FG, Korobelnik JF, Lanzetta P, Mitchell P, Schmidt-Erfurth U, Wolf S, Markabi S, Schmidli H, Weichselberger A (2010) The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: Outcomes of a drug and disease model. Invest Ophthalmol Vis Sci 51:405–412PubMedCrossRef
8.
go back to reference Gerding H (2010) Treatment of wet AMD with less than 12 injections of ranibizumab per year. Klin Monatsbl Augenheilkd 227:294–297PubMedCrossRef Gerding H (2010) Treatment of wet AMD with less than 12 injections of ranibizumab per year. Klin Monatsbl Augenheilkd 227:294–297PubMedCrossRef
9.
go back to reference Mitchell P, Korobelnik JF, Lanzetta P, Holz FG, Prünte C, Schmidt-Erfurth U, Tano Y, Wolf S (2010) Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials. Br J Ophthalmol 94:2–13PubMedCrossRef Mitchell P, Korobelnik JF, Lanzetta P, Holz FG, Prünte C, Schmidt-Erfurth U, Tano Y, Wolf S (2010) Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials. Br J Ophthalmol 94:2–13PubMedCrossRef
10.
go back to reference Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N, PIER Study Group (2008) Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 1. Am J Ophthalmol 145:239–248PubMedCrossRef Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N, PIER Study Group (2008) Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 1. Am J Ophthalmol 145:239–248PubMedCrossRef
11.
go back to reference Simader C, Bolz M, Ritter I, Golbaz I, Ahlers C, Schmidt-Erfurth U (2009) Comparison of treatment effects of ranibizumab on visual acuity, retinal thickness and retinal morphology when administered monthly versus quarterly with different dosing regimens in the EXCITE trial. ARVO 2009 abstract #351 @arvo.org and presentation 5.5.2009 Simader C, Bolz M, Ritter I, Golbaz I, Ahlers C, Schmidt-Erfurth U (2009) Comparison of treatment effects of ranibizumab on visual acuity, retinal thickness and retinal morphology when administered monthly versus quarterly with different dosing regimens in the EXCITE trial. ARVO 2009 abstract #351 @arvo.org and presentation 5.5.2009
12.
go back to reference Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG (2009) A phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology 116:1731–1739PubMedCrossRef Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG (2009) A phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology 116:1731–1739PubMedCrossRef
13.
go back to reference Eter N, Meyer CH, Holz FG, Amoaku W (2009) 12-months results of the SUSTAIN study: Safety and efficacy of ranibizumab treatment in patients with neovascular age related macular degeneration. EURETINA, Nice, 15.5.2009 Eter N, Meyer CH, Holz FG, Amoaku W (2009) 12-months results of the SUSTAIN study: Safety and efficacy of ranibizumab treatment in patients with neovascular age related macular degeneration. EURETINA, Nice, 15.5.2009
14.
go back to reference 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 143:566–583PubMedCrossRef 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 143:566–583PubMedCrossRef
15.
go back to reference Querques G, Azrya S, Martinelli D, Berboucha E, Feldmann A, Pece A, Coscas G, Soubrane G, Souied EH (2010) Ranibizumab for exudative age-related macular degeneration: 24-month outcome from a single-centre institutional setting. Br J Ophthalmol 94:292–296PubMedCrossRef Querques G, Azrya S, Martinelli D, Berboucha E, Feldmann A, Pece A, Coscas G, Soubrane G, Souied EH (2010) Ranibizumab for exudative age-related macular degeneration: 24-month outcome from a single-centre institutional setting. Br J Ophthalmol 94:292–296PubMedCrossRef
16.
go back to reference Kang S, Roh YJ (2009) One-year results of intravitreal ranibizumab for neovascular age-related macular degeneration and clinical responses of various subgroups. Jpn J Ophthalmol 53:389–395PubMedCrossRef Kang S, Roh YJ (2009) One-year results of intravitreal ranibizumab for neovascular age-related macular degeneration and clinical responses of various subgroups. Jpn J Ophthalmol 53:389–395PubMedCrossRef
17.
go back to reference 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 148:409–413PubMedCrossRef 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 148:409–413PubMedCrossRef
18.
go back to reference Rothenbühler S, Waeber D, Brinkmann CK, Wolf S, Wolf-Schnurbusch UEK (2009) Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration. Ophthalmologica 223:383–389CrossRef Rothenbühler S, Waeber D, Brinkmann CK, Wolf S, Wolf-Schnurbusch UEK (2009) Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration. Ophthalmologica 223:383–389CrossRef
19.
go back to reference Blackhurst DW, Maguire MG (1989) Reproducibility of refraction and visual acuity measurements under a standard protocol. The Macular Photocoagulation Study Group. Retina 9:163–169PubMedCrossRef Blackhurst DW, Maguire MG (1989) Reproducibility of refraction and visual acuity measurements under a standard protocol. The Macular Photocoagulation Study Group. Retina 9:163–169PubMedCrossRef
20.
go back to reference Leinonen J, Laakkonen E, Laatikainen L (2005) Random measurement error in visual acuity measurements in clinical settings. Acta Ophthalmol Scand 83:328–332PubMedCrossRef Leinonen J, Laakkonen E, Laatikainen L (2005) Random measurement error in visual acuity measurements in clinical settings. Acta Ophthalmol Scand 83:328–332PubMedCrossRef
21.
go back to reference Ernst BJ, Barkmeier AJ, Akduman L (2010) Optical coherence tomography-based intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Int Ophthalmol 30:267–270PubMedCrossRef Ernst BJ, Barkmeier AJ, Akduman L (2010) Optical coherence tomography-based intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Int Ophthalmol 30:267–270PubMedCrossRef
22.
go back to reference 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 148:43–58PubMedCrossRef 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 148:43–58PubMedCrossRef
23.
go back to reference Krebs J, Hagen S, Brannath W, Haas P, Womastek I, de Salvo G, Ansari-Shahrezaei S, Binder S (2010) Repeatability and reproducibility of retinal thickness measurements by optical coherence tomography in age-related macular degeneration. Ophthalmology 117:1577–1584PubMedCrossRef Krebs J, Hagen S, Brannath W, Haas P, Womastek I, de Salvo G, Ansari-Shahrezaei S, Binder S (2010) Repeatability and reproducibility of retinal thickness measurements by optical coherence tomography in age-related macular degeneration. Ophthalmology 117:1577–1584PubMedCrossRef
24.
go back to reference Taban M, Williams D, Smith SD, Kaiser PK (2010) Assessing the reliability of automated OCT retinal measurements in patients with choroidal neovascularization due to age-related macular degeneration. Ophthalmic Surg Lasers Imaging 41:166–174PubMedCrossRef Taban M, Williams D, Smith SD, Kaiser PK (2010) Assessing the reliability of automated OCT retinal measurements in patients with choroidal neovascularization due to age-related macular degeneration. Ophthalmic Surg Lasers Imaging 41:166–174PubMedCrossRef
Metadata
Title
Results of flexible ranibizumab treatment in age-related macular degeneration and search for parameters with impact on outcome
Authors
Heinrich Gerding
Vlassios Loukopoulos
Juliane Riese
Lars Hefner
Melanie Timmermann
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 5/2011
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-011-1636-6

Other articles of this Issue 5/2011

Graefe's Archive for Clinical and Experimental Ophthalmology 5/2011 Go to the issue