Intravitreal ranibizumab for neovascular age-related macular degeneration in clinical practice: five-year treatment outcomes
Abstract
Background Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are the established standard of care for neovascular age-related macular degeneration (nAMD). However, data on long-term outcomes of this therapy are limited. The purpose of this study was to assess the visual and anatomical outcomes and safety profile of intravitreal ranibizumab in treating nAMD over a period of five years.Methods 208 patients (208 eyes) were included in this retrospective case series study. Intervention was an "as-needed" treatment model. Visual acuity (VA), central macular thickness (CMT), ophthalmic examination, and adverse events (AEs) were assessed in each visit. Snellen VA was converted to Early Treatment Diabetic Retinopathy Study letters for analysis.Results The average VA improved by 1.9 letters after one year (p = 0.017), and decreased by 2.4 letters over five years of treatment (p = 0.043). At the end of year five, 11.1 % of patients (23/208) had improved VA by more than 15 letters and 68.8 % (143/208) had VA improvement or loss less than or equal to 15 letters, while 20.2 % of patients (42/208) had a loss of more than 15 letters. Patients with VA of less than 35 letters at baseline showed significant VA improvement after five years of treatment. There was a positive relationship between injection numbers and VA improvement over the five-year period, after adjusting for age and baseline VA (p < 0.0005). Mean CMT decreased by 28.3 μm (p < 0.0005) over five years. Ocular AEs, serious adverse events (SAEs), and systemic SAEs occurred in 4.6 %, 0.48 %, and 2 % of patients, respectively, during the follow-up period.Conclusions The use of intravitreal ranibizumab in an as-needed treatment regimen over a five-year period was effective in maintaining vision in patients with nAMD and in reducing macular thickness, with a relatively low rate of adverse and serious adverse events.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Multiple large retrospective or registry studies have published 4- and 5-year results.
“Several large-scale retrospective or registry studies have reported 4- and 5-year outcomes”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [24]
In an Australian retrospective review, patients frequently stop attending care shortly after their vision declines.
“patients who stop returning for care often do so soon after losing vision”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [24]
Patients with better vision are over-represented in retrospective/registry studies of long-term anti-VEGF outcomes.
“so that patients with better vision are over-represented in these studies.”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [24]
Cites
STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT
Martin Bland, J., & Altman, D. (1986) · The Lancet · doi:10.1016/s0140-6736(86)90837-8 · Cited by 47,965 · see citing works
Beckett, A. H., Rowland, M., & TURNER, P. (1965) · The Lancet · doi:10.1016/s0140-6736(65)91037-8 · Cited by 16,917 · see citing works
Ranibizumab for Neovascular Age-Related Macular Degeneration
Rosenfeld, P. J., Brown, D. M., Heier, J. S., Boyer, D. S., Kaiser, P. K., Chung, C. Y., & Kim, R. Y. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054481 · Cited by 5,886 · see citing works
Ranibizumab and bevacizumab for neovascular age-related macular degeneration
(2011) · New England Journal of Medicine · doi:10.1056/nejmoa1102673 · Cited by 2,669 · see citing works
Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration
Heier, J. S., Brown, D. M., Chong, V., Korobelnik, J.-F., Kaiser, P. K., Nguyen, Q. D., Kirchhof, B., Ho, A., Ogura, Y., Yancopoulos, G. D., et al. (2012) · Ophthalmology · doi:10.1016/j.ophtha.2012.09.006 · Cited by 2,485 · see citing works
Age-related macular degeneration
Lim, L. S., Mitchell, P., Seddon, J. M., Holz, F. G., & Wong, T. Y. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60282-7 · Cited by 1,764 · see citing works
Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration
Martin, D. F., Maguire, M. G., Fine, S. L., Ying, G.-S., Jaffe, G. J., Grunwald, J. E., Toth, C., Redford, M., & Ferris, F. L. (2012) · Ophthalmology · doi:10.1016/j.ophtha.2012.03.053 · Cited by 1,715 · see citing works
Brown, D. M., Michels, M., Kaiser, P. K., Heier, J. S., Sy, J. P., & Ianchulev, T. (2009) · Ophthalmology · doi:10.1016/j.ophtha.2008.10.018 · Cited by 1,318 · see citing works
Lalwani, G. A., Rosenfeld, P. J., Fung, A. E., Dubovy, S. R., Michels, S., Feuer, W. J., Davis, J. L., Flynn, H. W., & Esquiabro, M. (2009) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2009.01.024 · Cited by 876 · see citing works
Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration
Chakravarthy, U., Harding, S. P., Rogers, C. A., Downes, S. M., Lotery, A. J., Wordsworth, S., & Reeves, B. C. (2012) · Ophthalmology · doi:10.1016/j.ophtha.2012.04.015 · Cited by 779 · see citing works
The Natural History and Prognosis of Neovascular Age-Related Macular Degeneration
Wong, T., Chakravarthy, U., Klein, R., Mitchell, P., Zlateva, G., Buggage, R., Fahrbach, K., Probst, C., & Sledge, I. (2008) · Ophthalmology · doi:10.1016/j.ophtha.2007.03.008 · Cited by 601 · see citing works
NOVEL METHOD FOR ANALYZING SNELLEN VISUAL ACUITY MEASUREMENTS
Gregori, N. Z., Feuer, W. J., & Rosenfeld, P. J. (2010) · Retina · doi:10.1097/iae.0b013e3181d87e04 · Cited by 525 · see citing works
Prevalence of Age-Related Macular Degeneration in the US Population
Klein, R. (2011) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2010.318 · Cited by 512 · see citing works
Wolf, S., Ćeklić, L., Brinkmann, C. K., Iliev, M. E., Frey, M., Rothenbuehler, S. P., Enzmann, V., & Wolf, S. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2970 · Cited by 426 · see citing works
Mitchell, P. L. R., Jf, K., Lanzetta, P., Holz, F. G., Prünte, C. F., Schmidt-Erfurth, U. M., Tano, Y., & Wolf, S. (2009) · British Journal of Ophthalmology · doi:10.1136/bjo.2009.159160 · Cited by 297 · see citing works
Giani, A., Cigada, M., Choudhry, N., Deiro, A. P., Oldani, M., Pellegrini, M., Invernizzi, A., Duca, P., Miller, J. W., & Staurenghi, G. (2010) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2010.06.025 · Cited by 183 · see citing works
Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-related Macular Degeneration
Chang, A., Li, H., Broadhead, G., Hong, T., Schlub, T. E., Wijeyakumar, W., & Zhu, M. (2013) · Ophthalmology · doi:10.1016/j.ophtha.2013.08.035 · Cited by 149 · see citing works
Self-citationRasmussen, A., Bloch, S. B., Fuchs, J., Hansen, L. H., Larsen, M., LaCour, M., Lund-Andersen, H., & Sander, B. (2013) · Ophthalmology · doi:10.1016/j.ophtha.2013.05.018 · Cited by 116 · see citing works
Joeres, S., Tsong, J. W., Updike, P. G., Collins, A. T., Dustin, L., Walsh, A. C., Romano, P. W., & Sadda, S. R. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0179 · Cited by 103 · see citing works
Falk, M. K., Kemp, H., & Sørensen, T. L. (2012) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2012.06.031 · Cited by 96 · see citing works
Golbaz, I., Ahlers, C., Stock, G., Schütze, C., Schriefl, S. M., Schlanitz, F. G., Simader, C., Prünte, C. F., & Schmidt-Erfurth, U. M. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-5018 · Cited by 76 · see citing works
Brown, D. M., Tuomi, L., & Shapiro, H. (2012) · Retina · doi:10.1097/iae.0b013e318263cedf · Cited by 74 · see citing works
CURRENT KNOWLEDGE AND TRENDS IN AGE-RELATED MACULAR DEGENERATION
Vélez-Montoya, R., Oliver, S. C. N., Olson, J. L., Fine, S. L., Mandava, N., & Quiroz-Mercado, H. (2012) · Retina · doi:10.1097/iae.0b013e318271f265 · Cited by 66 · see citing works
NO CASES OF ENDOPHTHALMITIS AFTER 20,293 INTRAVITREAL INJECTIONS IN AN OPERATING ROOM SETTING
Brynskov, T., Kemp, H., & Sørensen, T. L. (2013) · Retina · doi:10.1097/iae.0000000000000071 · Cited by 64 · see citing works
Intravitreal injections: is there benefit for a theatre setting?
Abell, R. G., Kerr, N. M., Allen, P., & Vote, B. J. T. (2012) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2012-302030 · Cited by 63 · see citing works
Folgar, F. A., Jaffe, G. J., Ying, G., Maguire, M. G., & Toth, C. A. (2014) · Ophthalmology · doi:10.1016/j.ophtha.2014.04.020 · Cited by 39 · see citing works
Pushpoth, S., Sykakis, E., Merchant, K., Browning, A. C., Gupta, R., & Talks, J. S. (2012) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2012-302167 · Cited by 38 · see citing works
SCHACHAT, A. P. (2013) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2013.04.009 · Cited by 31 · see citing works
Hatef, E., Khwaja, A. A., Rentiya, Z., Ibrahim, M., Shulman, M., Türkçüoğlu, P., Sepah, Y. J., Wang, J., Channa, R., Bittencourt, M. G., et al. (2012) · Journal of Ophthalmology · doi:10.1155/2012/354783 · Cited by 27 · see citing works
Krebs, I., Hagen, S., Smretschnig, E., Womastek, I., Brannath, W., & Binder, S. (2011) · British Journal of Ophthalmology · doi:10.1136/bjo.2010.194662 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Maguire, M. G., Martin, D. F., Ying, G.-S., Jaffe, G. J., Daniel, E., Grunwald, J. E., Toth, C. A., Ferris, F. L., & Fine, S. L. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2016.03.045 · Cited by 708 · see citing works
Ohji, M., Takahashi, K. A., Okada, A. A., Kobayashi, M., Matsuda, Y., Terano, Y., for the ALTAIR Investigators, Ohji, M., Hanemoto, T., Kaga, T., et al. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01236-x · Cited by 255 · see citing works
Lanzetta, P., & Loewenstein, A. (2017) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-017-3647-4 · Cited by 179 · see citing works
Ranibizumab for the treatment of wet AMD: a summary of real-world studies
Chong, V. N. (2015) · Eye · doi:10.1038/eye.2015.217 · Cited by 138 · see citing works
ElSheikh, R. H., Chauhan, M. Z., & Sallam, A. B. (2022) · Biomolecules · doi:10.3390/biom12111629 · Cited by 96 · see citing works
Molecular mechanisms of diabetic retinopathy: Potential therapeutic targets
El‐Remessy, A. B., Coucha, M. M., Elshaer, S. L., Eldahshan, W., & Mysona, B. A. (2015) · Middle East African Journal of Ophthalmology · doi:10.4103/0974-9233.154386 · Cited by 76 · see citing works
Daïen, V., Finger, R. P., Talks, J. S., Mitchell, P., Wong, T. Y., Sakamoto, T., Eldem, B., & Korobelnik, J. (2020) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2020-317434 · Cited by 76 · see citing works
Adrean, S. D., Chaili, S., Ramkumar, H., Pirouz, A., & Grant, S. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2018.01.012 · Cited by 70 · see citing works
Arevalo, J. F., Lasave, A. F., Wu, L., Acón, D., Berrocal, M. H., Diaz-Llopis, M., Gallego-Pinazo, R., Serrano, M. A., Alezzandrini, A. A., Rojas, S., et al. (2016) · Retina · doi:10.1097/iae.0000000000000827 · Cited by 60 · see citing works
Haga, A., Kawaji, T., Ideta, R., Inomata, Y., & Tanihara, H. (2017) · Acta Ophthalmologica · doi:10.1111/aos.13607 · Cited by 45 · see citing works
Six-year outcomes in neovascular age-related macular degeneration with ranibizumab
Jacob, J. A., Brié, H., LEYS, A. M., Levecq, L., Mergaerts, F., Denhaerynck, K., Vancayzeele, S., Craeyveld, E. V., Abraham, I. L., & MacDonald, K. (2017) · International Journal of Ophthalmology · doi:10.18240/ijo.2017.01.14 · Cited by 37 · see citing works
Nguyen, C. L., Gillies, M. C., Nguyen, V., Daïen, V., Cohn, A., Banerjee, G., & Arnold, J. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2018.11.036 · Cited by 34 · see citing works
Sridhar, J. S., Hsu, J., Shahlaee, A., Garg, S. J., Spirn, M. J., Fineman, M. S., & VANDER, J. F. (2016) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2016.0045 · Cited by 30 · see citing works
Sii, S. S. Z., Aspinall, P., Borooah, S., & Dhillon, B. (2017) · Eye · doi:10.1038/eye.2017.271 · Cited by 29 · see citing works
Treatment of Exudative Age-related Macular Degeneration: Focus on Aflibercept
García‐Layana, A., Figueroa, M. S., Araiz, J., Ruiz‐Moreno, J. M., Gómez‐Ulla, F., Arias, L., & Reiter, N. (2015) · Drugs & Aging · doi:10.1007/s40266-015-0300-y · Cited by 29 · see citing works
Qin, V. L., Young, J., Silva, F. Q. D. P. A., Conti, F. F., & Singh, R. P. (2017) · Retina · doi:10.1097/iae.0000000000001753 · Cited by 23 · see citing works
Itraconazole in the treatment of tinea capitis.
Degreef, H. J. (1996) · PubMed · Cited by 19 · see citing works
Pedrosa, A. C., Reis-Silva, A., Pinheiro-Costa, J., Beato, J. N., Freitas‐da‐Costa, P., Falcão, M. S., Falcão‐Reis, F., & Carneiro, Â. M. (2016) · Clinical ophthalmology · doi:10.2147/opth.s90913 · Cited by 17 · see citing works
Clinical Trials and Future Outlooks of the Port Delivery System with Ranibizumab: A Narrative Review
Lowater, S. J., Grauslund, J., Subhi, Y., & Vergmann, A. S. (2023) · Ophthalmology and Therapy · doi:10.1007/s40123-023-00843-5 · Cited by 16 · see citing works
Wu, T., & Kung, Y. (2017) · Retina · doi:10.1097/iae.0000000000001453 · Cited by 16 · see citing works
Voluntary Exercise Suppresses Choroidal Neovascularization in Mice.
Makin, R. D., Argyle, D., Hirahara, S., Nagasaka, Y., Zhang, M., Yan, Z., Kerur, N., Ambati, J., & Gelfand, B. D. (2020) · PubMed Central · doi:10.1167/iovs.61.5.52 · Cited by 16 · see citing works
Chhablani, J. K., Paulose, R. M., Lasave, A. F., Wu, L., Carpentier, C., Maia, M., Lujan, S., Rojas, S., Serrano, M. A., Berrocal, M. H., et al. (2017) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2017-310411 · Cited by 13 · see citing works
Spooner, K., Hong, T., Nair, R., Chow, N. C. C., Broadhead, G., Wijeyakumar, W., & Chang, A. (2019) · Acta Ophthalmologica · doi:10.1111/aos.14046 · Cited by 11 · see citing works
Self-citationHujanen, P., Ruha, H., Lehtonen, E., Pirinen, I., Huhtala, H., Vaajanen, A., Syvänen, U., Tuulonen, A., & Uusitalo‐Järvinen, H. (2023) · BMJ Open Ophthalmology · doi:10.1136/bmjophth-2023-001328 · Cited by 10 · see citing works
Gabrielle, P., Nguyen, V., Arnold, J., Bhandari, S., Viola, F., Tigchelaar-Besling, O. A. M., Garay‐Aramburu, G., O’Toole, L., Cheung, C. M. G., Barthelmes, D., et al. (2021) · Translational Vision Science & Technology · doi:10.1167/tvst.10.13.5 · Cited by 10 · see citing works
Sharma, S., & Ma, K. (2018) · International Journal of Ophthalmology & Eye Science · doi:10.19070/2332-290x-1800074 · Cited by 9 · see citing works
LEYS, A. M., Ramboer, E., Favreau, M., Denhaerynck, K., MacDonald, K., Abraham, I. L., & Brié, H. (2020) · Clinical ophthalmology · doi:10.2147/opth.s242547 · Cited by 5 · see citing works
Meira, J., Carneiro, J., Madeira, C., Falcão, M. S., Beato, J. N., Correia, S., Falcão‐Reis, F., & Carneiro, Â. M. (2020) · Archivos de la Sociedad Española de Oftalmología · doi:10.1016/j.oftal.2020.03.020 · Cited by 5 · see citing works
Stattin, M., Forster, J., Ahmed, D., Haas, A., Graf, A. C., Krepler, K., & Ansari‐Shahrezaei, S. (2020) · Journal of Ophthalmology · doi:10.1155/2020/8345850 · Cited by 4 · see citing works
DIABETIC RETINOPATHY: AN INCLUSIVE REVIEW ON CURRENT TREATMENT AND MANAGEMENT APPROACHES
Jyothi, S. L., & Vishal Gupta, N. (2018) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2018.v11i11.26949 · Cited by 4 · see citing works
Photosensitizer formulations in photodynamic therapy of age-related macular degeneration
Beirão, S., Pereira, P. M. R., Fernandes, R., & Tomé, J. P. C. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.117105 · Cited by 3 · see citing works
Meira, J., Carneiro, J., Madeira, C., Falcão, M. S., Beato, J. N., Correia, S., Falcão‐Reis, F., & Carneiro, Â. M. (2020) · Archivos de la Sociedad Española de Oftalmología (English Edition) · doi:10.1016/j.oftale.2020.03.001 · Cited by 3 · see citing works
Park, Y. J., Son, G. S., Kim, Y. J., Kim, J.-G., Yoon, Y. H., & Lee, J. Y. (2018) · Journal of the Korean Ophthalmological Society · doi:10.3341/jkos.2018.59.12.1142 · Cited by 3 · see citing works
Carnevali, A., Chisari, D., Gioia, R., Mancini, A., Borselli, M., Macrì, R., Lucisano, A., Scalzo, G. C., Frizziero, L., Scorcia, V., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15103561 · Cited by 2 · see citing works
Zhang, P., Shi, J., Gao, L., & Shu, X. (2023) · Arquivos Brasileiros de Oftalmologia · doi:10.5935/0004-2749.20230018 · Cited by 1 · see citing works
Chaili, S., & Adrean, S. D. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.81466 · Cited by 1 · see citing works
Sarao, V., Parravano, M., Veritti, D., Arias, L., Varano, M., & Lanzetta, P. (2015) · Retina · doi:10.1097/iae.0000000000000751 · Cited by 31 · see citing works
- Authors
- Zhu, M., Chew, J. K., Broadhead, G. K., Luo, K., Joachim, N., Hong, T., Syed, A., & Chang, A. A.
- Affiliations
- The University of Sydney (AU)
- Macquarie University (AU)
- Corresponding author
- Chang, Andrew A.
- Venue
- Graefe's Archive for Clinical and Experimental Ophthalmology
- Published
- 2014-09-10
- Volume
- 253
- Issue
- 8
- Pages
- 1217-1225
- ISSN
- 0721-832X (ISSN-L)
- 1435-702X
- OpenAlex
- W2005009598
- Cited by
- 38
- References
- 30
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 7 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 5
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Graefe s Archive for Clinical and Experimental Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- ranibizumab, neovascular age-related macular degeneration, intravitreal anti-VEGF therapy, as-needed treatment, visual acuity outcomes, central macular thickness, long-term treatment outcomes, adverse events, injection frequency
- MeSH terms
- Ranibizumab, Aged, Aged, 80 and over, Female, Fluorescein Angiography, Follow-Up Studies, Humans, Male, Retina, Retrospective Studies, Visual Acuity, Treatment Outcome, Angiogenesis Inhibitors, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Wet Macular Degeneration, Intravitreal Injections, Subretinal Fluid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
