Cited by 748Retinal Diseases and TreatmentsOcular Diseases and Behçet’s SyndromeRetinal and Macular Surgery

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Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial

Open access

Chakravarthy, Usha, Harding, Simon P, Rogers, Chris A, Downes, Susan M, Lotery, Andrew J, Culliford, Lucy A, Reeves, Barnaby C·2013·The Lancet

DOI 10.1016/s0140-6736(13)61501-9

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Abstract

BACKGROUND: Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. METHODS: In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. FINDINGS: Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1·63 letters, -4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 [6%] of 314 participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1·69, 95% CI 0·80-3·57; p=0·16), or those given continuous (12 [4%] of 308) and discontinuous treatment (20 [7%] of 302; 0·56, 0·27-1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22-1·03; p=0·05), but did not differ by drug group (0·96, 0·46-2·02; p=0·91). INTERPRETATION: Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

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Background
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Method
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MethodResultInfluential
A prospective, observational, open‐label, multicentre study to investigate the daily treatment practice of ranibizumab in patients with neovascular age‐related macular degeneration
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BackgroundInfluential
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Background
Identifying Diabetic Macular Edema and Other Retinal Diseases by Optical Coherence Tomography Image and Multiscale Deep Learning
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Phase I clinical studies with WR-2721.
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Method
Long-term Visual Outcomes after Release from Protocol in Patients who Participated in the Inhibition of VEGF in Age-related Choroidal Neovascularisation (IVAN) Trial
Evans, R. N., Reeves, B. C., Phillips, D., Muldrew, K. A., Rogers, C., Harding, S. P., & Chakravarthy, U. (2020) · Ophthalmology · doi:10.1016/j.ophtha.2020.03.020 · Cited by 28
“A factorial design was used with study eyes randomized to 1 of 2 anti-VEGF drugs ranibizumab or bevacizumab, and monthly versus treatment as needed.(8) After release from the IVAN protocol (last participant released from protocol in October 2012), all patients were managed within the National Health Service with free…”
MethodSelf-citation
A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies
Arranz-Romera, A., Hernández, M., Checa-Casalengua, P., García‐Layana, A., Molina-Martínez, I. T., Recalde, S., Young, M. J., Tucker, B. A., Herrero‐Vanrell, R., Fernández‐Robredo, P., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14010050 · Cited by 28
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“In this regard, several studies have demonstrated reduced systemic VEGF levels in patients receiving intravitreal anti-VEGF, but the systemic effect appears to be most obvious with bevacizumab and lowest with ranibizumab.(12,13) Another line of evidence came from studies that used Medicare case records.”
Result
MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR–TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Mantel, I., Dirani, A., Zola, M., Parvin, P., Massougnes, S. D., & Bergin, C. (2018) · Retina · doi:10.1097/iae.0000000000002054 · Cited by 27
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Self-citation
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Self-citation
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Robert, M.-C., Frenette, M., Zhou, C., Yan, Y., Chodosh, J., Jakobiec, F. A., Stagner, A. M., Vavvas, D. G., Dohlman, C. H., & Paschalis, E. I. (2016) · Translational Vision Science & Technology · doi:10.1167/tvst.5.2.11 · Cited by 27
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Result
Changes in intraocular pressure in study and fellow eyes in the IVAN trial
Foss, A. J. E., Scott, L. J., Rogers, C. A., Reeves, B. C., Ghanchi, F. D., Gibson, J. M., & Chakravarthy, U. (2016) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2015-307595 · Cited by 26
Self-citation
Recommended Guidelines for Use of Intravitreal Aflibercept With a Treat-and-Extend Regimen for the Management of Neovascular Age-Related Macular Degeneration in the Asia-Pacific Region: Report From a Consensus Panel
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Serum Vascular Endothelial Growth Factor Levels in the IVAN Trial; Relationships with Drug, Dosing, and Systemic Serious Adverse Events
Rogers, C. A., Scott, L. J., Reeves, B. C., Downes, S. M., Lotery, A. J., Dick, A. D., & Chakravarthy, U. (2017) · Ophthalmology Retina · doi:10.1016/j.oret.2017.05.015 · Cited by 26
“It is also in accord with findings from the Comparison of Agerelated macular degeneration Treatment Trials (CATT), in which a higher frequency of SSAE in the pro re nata treatment arm was observed, and when combined with the IVAN trial in a meta-analysis reached statistical significance.(8,9) This finding raises the i…”
ResultSelf-citation
Mortality after a cerebrovascular event in age‐related macular degeneration patients treated with bevacizumab ocular injections
Hanhart, J., Comaneshter, D. S., & Vinker, S. (2018) · Acta Ophthalmologica · doi:10.1111/aos.13731 · Cited by 25
“For instance, the IVAN study investigators found that, over two years, the risk of non-fatal stroke and transient ischaemic attack (TIA) was higher with ranibizumab than with bevacizumab use (Chakravarthy et al. 2013).”
Treatment of age-related macular degeneration
Cheung, C. M. G., & Wong, T. Y. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61580-9 · Cited by 25
Single- and repeated-dose toxicity study of bevacizumab, ranibizumab, and aflibercept in ARPE-19 cells under normal and oxidative stress conditions
Sáenz-de-Viteri, M., Fernández‐Robredo, P., Hernández, M., Bezunartea, J., Reiter, N., Recalde, S., & García‐Layana, A. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.12.017 · Cited by 28
AFLIBERCEPT FOR THE TREATMENT OF RETINAL PIGMENT EPITHELIAL DETACHMENTS
He, L., Silva, R. A., Moshfeghi, D. M., Blumenkranz, M. S., & Leng, T. (2015) · Retina · doi:10.1097/iae.0000000000000749 · Cited by 25
Distribution of OCT Features within Areas of Macular Atrophy or Scar after 2 Years of Anti-VEGF Treatment for Neovascular AMD in CATT
Toth, C. A., Tai, V., Pistilli, M., Chiu, S. J., Winter, K. P., Daniel, E., Grunwald, J. E., Jaffe, G. J., Martin, D. F., Ying, G., et al. (2018) · Ophthalmology Retina · doi:10.1016/j.oret.2018.11.011 · Cited by 25
“001 68 (100) % Pixels 6 (3, 12) 27 (12, 54) 20 (10, 27) 3 (1, 9) <0.”
Influential
Identification of key genes and pathways in scleral extracellular matrix remodeling in glaucoma: Potential therapeutic agents discovered using bioinformatics analysis
Hu, D., Jiang, J., Lin, Z., Zhang, C., Moonasar, N., & Qian, S. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.52846 · Cited by 25
“In clinical ophthalmology, bevacizumab has been used widely in the management of ophthalmic diseases, including choroidal neovascularization, diabetic macular edema and macular edema [67].”
Background
Anti-VEGF-resistant subretinal fluid is associated with better vision and reduced risk of macular atrophy
Zarbin, M. A., Hill, L., Maunz, A., Gliem, M., & Stoilov, I. (2021) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2020-318688 · Cited by 25
“30 31 Although the posology of the HARBOR and FLUID 8 trials differed, the visual acuity results are similar in that persistent SRF of 200 µ m was not associated with a worse visual acuity outcome.”
Intravitreal steroid and anti-vascular endothelial growth agents for the management of retinal vein occlusion: evidence from randomized trials
Chatziralli, I., Nicholson, L., Sivaprasad, S., & Hykin, P. G. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1086744 · Cited by 25
Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders
Pfeil, J. M., Böhringer, D., Deissler, H. L., Faerber, L., Goepfert, J. C., Heiduschka, P., Kleeberger, S. M., Klettner, A., Krohne, T. U., Schneiderhan‐Marra, N., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0145375 · Cited by 25
The Vascular Endothelial Growth Factor Inhibitors Ranibizumab and Aflibercept Markedly Increase Expression of Atherosclerosis-Associated Inflammatory Mediators on Vascular Endothelial Cells
Arnott, C. G., Punnia-Moorthy, G., Tan, J. T. M., Sadeghipour, S., Bursill, C. A., & Patel, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150688 · Cited by 25
“For example, 2 year data from the IVAN trial [23], demonstrated a statistically significant increase in risk of systemic adverse events (including cardiovascular) with bevacizumab compared with ranibizumab.”
Background
Licence to save: a UK survey of anti-VEGF use for the eye in 2015
Shalaby, A. K., Lewis, K., Bush, K., Meredith, P. R., Simplicio, S. D., & Lockwood, A. (2016) · Eye · doi:10.1038/eye.2016.154 · Cited by 25
Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration
Christakis, P. G., Agrón, E., Klein, M. L., Clemons, T. E., Campbell, J. P., Ferris, F. L., Chew, E. Y., & Keenan, T. D. L. (2019) · Ophthalmology · doi:10.1016/j.ophtha.2019.11.016 · Cited by 25
Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration
García‐Layana, A., Figueroa, M. S., Arias, L., Araiz, J., Ruiz‐Moreno, J. M., García‐Arumí, J., Gómez‐Ulla, F., Gálvez, M. I. L., López, F. A. C., García-Campos, J. M., et al. (2015) · Journal of Ophthalmology · doi:10.1155/2015/412903 · Cited by 25
Visual acuity outcomes of anti-VEGF treatment for neovascular age-related macular degeneration in clinical trials
Yamashiro, K., Oishi, A., Hata, M., Takahashi, A., & Tsujikawa, A. (2021) · Japanese Journal of Ophthalmology · doi:10.1007/s10384-021-00869-x · Cited by 24
Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia
Belete, G. T., Zhou, L., Li, K. K., So, P., Wai, C., & Lam, T. C. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1403844 · Cited by 24
Insulin-Like Growth Factor-1 and Anti-Vascular Endothelial Growth Factor in Retinopathy of Prematurity: Has the Time Come
Stahl, A., Hellström, A., & Smith, L. E. H. (2014) · Neonatology · doi:10.1159/000365132 · Cited by 24
Macular Atrophy of the Retinal Pigment Epithelium in Patients with Neovascular Age-Related Macular Degeneration: What is the Link? Part I: A Review of Disease Characterization and Morphological Associations
Horani, M., Mahmood, S., & Aslam, T. M. (2019) · Ophthalmology and Therapy · doi:10.1007/s40123-019-0177-7 · Cited by 24
“utilized OCT in addition to CFP and FFA for atrophy assessment [12, 16, 19, 24].”
Method
Health economic evaluation in ophthalmology
Atik, A., Barton, K., Azuara‐Blanco, A., & Kerr, N. M. (2020) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2020-316880 · Cited by 24
Real‐world treatment outcomes of neovascular Age‐related Macular Degeneration in the Netherlands
Verbraak, F. D., Ponsioen, D. L., Tigchelaar-Besling, O. A. M., Nguyen, V., Gillies, M. C., Barthelmes, D., & Klaver, C. C. W. (2020) · Acta Ophthalmologica · doi:10.1111/aos.14712 · Cited by 24
Drug-related adverse effects of antivascular endothelial growth factor agents
Iyer, P. G., & Albini, T. A. (2021) · Current Opinion in Ophthalmology · doi:10.1097/icu.0000000000000757 · Cited by 24
“The IVAN trial at 2 years found that the frequency of arteriothrombotic events or hospital admission did not differ between the ranibizumab and bevacizumab groups [12].”
Background
Investigation of satisfaction with short-term outcomes after switching to faricimab to treat neovascular age-related macular degeneration
Hikichi, T. (2023) · Japanese Journal of Ophthalmology · doi:10.1007/s10384-023-01024-4 · Cited by 24
Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions
Biagi, C., Conti, V., Montanaro, N., Melis, M., Buccellato, E., Donati, M., Covezzoli, A., Amato, R., Pazzi, L., Venegoni, M., et al. (2014) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-014-1755-1 · Cited by 24
“On the contrary, 1-year data from the IVAN study [11] suggest an increased risk of stroke with ranibizumab, whereas no differences were found in the 2-year IVAN report, as well as in GEFAL and MANTA efficacy trials.”
Treatment as Required versus Regular Monthly Treatment in the Management of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis
Schmucker, C. M., Rücker, G., Sommer, H., Virgili, G., Loke, Y. K., Oeller, P., Agostini, H., & Ehlken, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137866 · Cited by 24
“with Subfoveal nAMD])[12, 13] and one in Europe (IVAN).[10, 11] One of these trials was sponsored by the pharmaceutical industry.”
BackgroundMethodResultInfluential
Real world evidence of use of anti-VEGF therapy in Denmark
Vorum, H., Olesen, T. K., Zinck, J., & Hedegaard, M. S. (2016) · Current Medical Research and Opinion · doi:10.1080/03007995.2016.1221803 · Cited by 24
The fate of eyes with wet AMD beyond four years of anti-VEGF therapy
Garweg, J. G., Zirpel, J. J., Gerhardt, C., & Pfister, I. B. (2018) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-018-3907-y · Cited by 23
Complete RPE and outer retinal atrophy in patients receiving anti-VEGF treatment for neovascular age-related macular degeneration
Eng, V., Rayess, N., Nguyen, H. V., & Leng, T. (2020) · PLoS ONE · doi:10.1371/journal.pone.0232353 · Cited by 28
“1%) of eyes in the IVAN trial had baseline cRORA[27,28].”
Background
Systemic safety of anti-VEGF drugs: a commentary
Scott, L. J., Chakravarthy, U., Reeves, B. C., & Rogers, C. A. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2015.991712 · Cited by 22
“1 Study characteristics A total of 15 randomized controlled trials with 11,754 participants were identified; six trials were head-to-head comparisons of ranibizumab and bevacizumab (Subramanian [9], CATT [10], IVAN [7], GEFAL [11], MANTA [12] and LUCAS [13]) and two trials, VIEW1 and VIEW2 [14], compared ranibizumab a…”
BackgroundMethodInfluentialSelf-citation
Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study
Yeung, S. L. A., Lam, H. S., & Schooling, C. M. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.005619 · Cited by 25
RESIDUAL CHOROIDAL VESSELS IN ATROPHY CAN MASQUERADE AS CHOROIDAL NEOVASCULARIZATION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Nesper, P. L., Lutty, G. A., & Fawzi, A. A. (2017) · Retina · doi:10.1097/iae.0000000000001863 · Cited by 23
Fellow Eye Status Is a Biomarker for the Progression Rate of Geographic Atrophy
Shen, L. L., Liu, F., Nardini, H. K. G., & Priore, L. V. D. (2018) · Ophthalmology Retina · doi:10.1016/j.oret.2018.11.013 · Cited by 23
GEOGRAPHIC ATROPHY INCIDENCE AND PROGRESSION AFTER INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS FOR AGE-RELATED MACULAR DEGENERATION
Eshtiaghi, A., Issa, M., Popovic, M. M., Muni, R. H., & Kertes, P. J. (2021) · Retina · doi:10.1097/iae.0000000000003207 · Cited by 23
The changing landscape for the management of patients with neovascular AMD: brolucizumab in clinical practice
Pearce, I., Amoaku, W. M. K., Bailey, C., Downey, L., Gale, R. P., Ghanchi, F. D., HAMILTON, R. D., Mahmood, S., Menon, G., Nosek, J., et al. (2022) · Eye · doi:10.1038/s41433-022-02008-3 · Cited by 23
Rate of vision loss in neovascular age-related macular degeneration explored
Real, J. P., Granero, G. E., Santis, M. O. D., Juárez, C. P., Palma, S. D., Kelly, S. P., & Luna, J. D. (2014) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-014-2885-y · Cited by 23
“Recent studies have demonstrated that PRN treatment with either ranibizumab or bevacizumab undertaken with monthly monitoring and immediate retreatment following disease recurrence are of broadly similar ophthalmic efficacy [8, 9].”
BackgroundInfluential
ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Tóth, L., Stevenson, M., & Chakravarthy, U. (2015) · Retina · doi:10.1097/iae.0000000000000583 · Cited by 23
Self-citation
The Architecture of Macular Neovascularizations Predicts Treatment Responses to Anti-VEGF Therapy in Neovascular AMD
Faatz, H., Rothaus, K., Ziegler, M., Book, M., Spital, G., Lange, C., & Lommatzsch, A. P. (2022) · Diagnostics · doi:10.3390/diagnostics12112807 · Cited by 22
Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2
Narayanan, R., Stewart, M., Das, T., Chhablani, J. K., Jalali, S., Ali, H., & Panchal, B. U. (2016) · Clinical ophthalmology · doi:10.2147/opth.s104459 · Cited by 22
“9,10 Bevacizumab is noninferior to ranibizumab for the treat-ment of exudative age-related macular degeneration, 17,18 but retinal vein occlusions are associated with higher intraocular VEGF concentrations, 19 so equivalence of bevacizumab and ranibizumab for vein occlusions cannot be automatically…”
Background
INTRAVITREAL AFLIBERCEPT AND RANIBIZUMAB INJECTIONS FOR TYPE 3 NEOVASCULARIZATION
Cho, H. J., Hwang, H. J., Kim, H. S., Han, J. I., Lee, D. W., & Kim, J. W. (2017) · Retina · doi:10.1097/iae.0000000000001862 · Cited by 22
Ranibizumab vs. aflibercept for wet age-related macular degeneration: network meta-analysis to understand the value of reduced frequency dosing
Szabo, S. M., Hedegaard, M. S., Chan, K., Thorlund, K., Christensen, R., Vorum, H., & Jansen, J. P. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1084909 · Cited by 21
Intravitreal Bevacizumab and Cardiovascular Risk in Patients with Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies
Mikačić, I., & Bosnar, D. (2016) · Drug Safety · doi:10.1007/s40264-016-0408-y · Cited by 21
ORCA study: real-world versus reading centre assessment of disease activity of neovascular age-related macular degeneration (nAMD)
Liakopoulos, S., Spital, G., Brinkmann, C. K., Schick, T., Ziemssen, F., Voegeler, J., Koch, M., Kirchhof, B., Holz, F. G., Pauleikhoff, D., et al. (2020) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2019-315717 · Cited by 21
Intravitreal ranibizumab versus aflibercept versus bevacizumab for macular oedema due to central retinal vein occlusion: the LEAVO non-inferiority three-arm RCT
Hykin, P. G., Prevost, A. T., Sivaprasad, S., Vasconcelos, J. C., Murphy, C., Kelly, J., Ramu, J., Alshreef, A., Flight, L., Pennington, B., et al. (2021) · Health Technology Assessment · doi:10.3310/hta25380 · Cited by 21
Self-citation
Die Anti-VEGF-Therapie bei der neovaskulären altersabhängigen Makuladegeneration – therapeutische Strategien
Gesellschaft, D. O. (2015) · Der Ophthalmologe · doi:10.1007/s00347-014-3222-x · Cited by 21
Comparative Safety and Tolerability of Anti-VEGF Therapy in Age-Related Macular Degeneration
Modi, Y. S., Tanchon, C., & Ehlers, J. P. (2015) · Drug Safety · doi:10.1007/s40264-015-0273-0 · Cited by 22
“Finally, while not an immediate ocular adverse event associated with anti-VEGF therapy, geographic atrophy (GA) has been reported in both IVAN and CATT to occur at a higher rate in patients receiving continuous rather than as-needed treatments [23, 66].”
BackgroundResultInfluential
The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care
on behalf of UK AMD EMR Users Group, Liew, G., Lee, A., Zarranz‐Ventura, J., STRATTON, I. M., Bunce, C., Chakravarthy, U., Lee, C., Keane, P. A., Sim, D. A., et al. (2016) · Eye · doi:10.1038/eye.2016.149 · Cited by 21
Self-citation
One-Year Outcomes after Switching to Faricimab in Eyes with Pretreated Neovascular Age-Related Macular Degeneration
Grimaldi, G., Ambresin, A., Pfister, I. B., Schild, C., Plasencia, C., Hatz, K. B., Stillenmunkes, R., Munk, M. R., Paris, A., Menghini, M., et al. (2025) · Ophthalmology Retina · doi:10.1016/j.oret.2025.03.015 · Cited by 20
Two‐year functional and anatomical results after converting treatment resistant eyes with exudative age‐related macular degeneration to aflibercept in accordance with a treat and extend protocol
Jørstad, Ø. K., Faber, R. T., & Moe, M. C. (2017) · Acta Ophthalmologica · doi:10.1111/aos.13480 · Cited by 20
“…with the antibody bevacizumab, approved for the treatment of several malignancies, has also proven to be an effective therapy for exudative AMD in studies like CATT and IVAN (Comparison of Age-related Macular Degeneration Treatments Trials Research G et al. 2012; Chakravarthy et al. 2013).”
Background
MANAGEMENT OF RETINAL PIGMENT EPITHELIUM TEAR DURING ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Mitchell, P., Rodríguez, F. J., Joussen, A. M., Koh, A., Eter, N., Wong, D. T., Korobelnik, J., & Okada, A. A. (2020) · Retina · doi:10.1097/iae.0000000000003083 · Cited by 22

Authors: Chakravarthy, U., Harding, S. P., Rogers, C. A., Downes, S. M., Lotery, A. J., Culliford, L. A., & Reeves, B. C.
Affiliations: Queen's University Belfast (GB)
Corresponding author: Chakravarthy, Usha
ORCID: Chakravarthy, Usha
Harding, Simon P
Rogers, Chris A
Downes, Susan M
Lotery, Andrew J
Culliford, Lucy A
Reeves, Barnaby C
Venue: The Lancet
Publisher: Elsevier BV
Published: 2013-10
Volume: 382
Issue: 9900
Pages: 1258-1267
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(13)61501-9
OpenAlex: W2154073405
Cited by: 748
References: 45
Citations by year: 2026: 13 · 2025: 36 · 2024: 36 · 2023: 36 · 2022: 33 · 2021: 84 · 2020: 66 · 2019: 44 · 2018: 74 · 2017: 66 · 2016: 90 · 2015: 77 · 2014: 75 · 2013: 13
FWCI: 84.02
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-sa/3.0/ (vor)
Locations: The Lancet (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion)
Research Portal (Queen's University Belfast) (submittedVersion, cc-by-nc-sa)
Bristol Research (University of Bristol) (submittedVersion, cc-by-nc-sa)
ePrints Soton (University of Southampton) (submittedVersion, cc-by-nc-sa)
Funders: National Institute for Health and Care Research (07/36/01)
Health Technology Assessment Programme (07/36/01, /36/01)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Health Sciences › Medicine › Ophthalmology › Retinal and Macular Surgery
Keywords: neovascular age-related macular degeneration, choroidal neovascularization, bevacizumab, ranibizumab, anti-VEGF therapy, intravitreal injection, treatment regimen comparison, best-corrected visual acuity, non-inferiority, arterial thrombotic events, long-term outcomes
MeSH terms: Bevacizumab, Ranibizumab, Aged, Female, Humans, Male, Middle Aged, Treatment Outcome, Choroidal Neovascularization, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Antibodies, Monoclonal, Humanized

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Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial

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