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

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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 FINDINGS: Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in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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Self-citation
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“However, this finding was not confirmed in the IVAN study which e709 showed that the type of anti-VEGF drug used made no difference to the development of GA (Chakravarthy et al. 2013).”
Result
Review of Guideline Recommendations for Optimal Anti-VEGF Therapy in Age-Related Macular Degeneration
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“The same conclusion is supported by the HARBOR, SEVEN-UP, and IVAN studies [94–96].”
Result
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Background
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“However, long-term use of anti-VEGF will not only reduce the efficacy, but may also lead to retinal hemorrhage, fibrosis and scarring, macular atrophy or retina map atrophy [9, 10].”
Background
The state-of-the-art pharmacotherapeutic management of neovascular age-related macular degeneration
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“vascularization (MNV) activity, such as intraretinal or subretinal fluid, subretinal hemorrhage, or exudation [15,16].”
Background
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“Furthermore, the treatment patterns of bevacizumab should be taken into account because injections on an as-needed basis would have a lower risk of serious systemic events than scheduled monthly injections.[15,17] This lower risk of ischaemic events that coincides with a lower versus higher dosage of bevacizumab has b…”
BackgroundMethodResultInfluential
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“Similarly, in the IVAN trial, 34% versus 26% showed progressive atrophy in the monthly versus PRN groups, respectively.[8, 13, 17]”
Method
[Atrophy of the macula in the context of its wet, age-related degeneration : An inescapable consequence of anti-VEGF therapy?]
Jg, G. (2016) · PubMed · doi:10.1007/s00347-016-0306-9 · Cited by 9
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“Multiple post-hoc analysis including those from the CATT and IVAN trials have demonstrated a negative association between large fluid fluctuations and visual acuity [23, 35].”
Method
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“Despite some disadvantages of OCT, the large majority of as-needed treatment decisions in RCTs have been based on OCT examinations (over 95% in the CATTstudy [3] and over 97% in the IVAN study [23]).”
Background
Enlargement rate of geographic atrophy before and after secondary CNV conversion with associated anti-VEGF treatment
Siedlecki, J., Koch, C., Schworm, B., Liegl, R. G.-H., Kreutzer, T. C., Kortuem, K., Schumann, R. G., Priglinger, S. G., & Wolf, A. (2021) · BMC Ophthalmology · doi:10.1186/s12886-020-01766-6 · Cited by 9
“However, retrospective analyses of large clinical trials, including CATT [5] and IVAN [19], Fig.”
Background
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“Recently, several authors have investigated morpho-functional changes after different VEGF treatments 17,18 .”
Background
Inner nuclear layer cystoid spaces are a poor prognostic factor in typical age-related macular degeneration and polypoidal choroidal vasculopathy
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“Monthly anti-VEGF injections and clinic visits for nAMD showed better functional and anatomical outcomes than the pro re nata (PRN) regimen [7, 8].”
Real-world use of ranibizumab for neovascular age-related macular degeneration in Taiwan
Chang, Y.-S., Lee, W. A., Lim, C.-C., Wang, S.-H., Hsu, S., Chen, Y.-C., Cheng, C.-Y., Teng, Y., Huang, Y.-H., Lai, C., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-25864-0 · Cited by 10
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Self-citation
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“The third and most common strategy is the treat-and-extend regimen (TAE), with its variant the treat-extend-stop (TES) method which we previously described [6, 13, 14].”
Background
Long-acting delivery and therapies for neovascular age-related macular degeneration
Rowe, L. W., & Ciulla, T. A. (2024) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2024.2374869 · Cited by 8
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Systemic Arterial and Venous Thrombotic Events Associated With Anti–Vascular Endothelial Growth Factor Injections: A Meta-Analysis
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Comparing different dosing regimens of bevacizumab in the treatment of neovascular macular degeneration: study protocol for a randomised controlled trial
Foss, A. J. E., Childs, M., Reeves, B. C., Empeslidis, T., Tesha, P. E., Dhar‐Munshi, S., Mughal, S., Culliford, L. A., Rogers, C. A., Tan, W., et al. (2015) · Trials · doi:10.1186/s13063-015-0608-2 · Cited by 8
“Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Cullifford LA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial.”
BackgroundMethodInfluentialSelf-citation
Real-World Outcomes of Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration in Turkey: A Multicenter Retrospective Study, Bosphorus Retina Study Group Report No: 1
Özkaya, A., Karabas, V. L., Alagöz, C., Alkın, Z., Artunay, Ö., Bölükbaşı, S., Demir, G., Demir, M., Demircan, A., Erden, B., et al. (2018) · Turkish Journal of Ophthalmology · doi:10.4274/tjo.31697 · Cited by 9
Erste Erfahrungen mit Brolucizumab bei neovaskulärer altersabhängiger Makuladegeneration und Therapierefraktärität unter der bisherigen Anti-VEGF-Therapie
Book, M., Ziegler, M., Rothaus, K., Faatz, H., Gutfleisch, M., Spital, G., Lommatzsch, A. P., & Pauleikhoff, D. (2021) · Der Ophthalmologe · doi:10.1007/s00347-021-01474-6 · Cited by 8
STRICT PRO RE NATA VERSUS TREAT-AND-EXTEND REGIMENS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Fang, H.-S., Bai, C., & Cheng, C. (2023) · Retina · doi:10.1097/iae.0000000000003690 · Cited by 8
NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH ADVANCED VISUAL LOSS TREATED WITH ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Vogel, R. N., Davis, D. B., Kimura, B. H., Rathinavelu, S., Graves, G. S., Szabó, A., & Han, D. P. (2016) · Retina · doi:10.1097/iae.0000000000001150 · Cited by 8
CD160 Expression in Retinal Vessels Is Associated With Retinal Neovascular Diseases
Henry, A., Boulagnon‐Rombi, C., Menguy, T., Giustiniani, J., Garbar, C., Mascaux, C., Labrousse, M., Milas, C., Barbe, C., Bensussan, A., et al. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-24021 · Cited by 8
Single-Dose Intravitreal Conbercept before Panretinal Photocoagulation as an Effective Adjunctive Treatment in Chinese Proliferative Diabetic Retinopathy
Zhang, Q., Zhang, T., Zhuang, H., Sun, Z., & Qin, Y. (2019) · Ophthalmologica · doi:10.1159/000495423 · Cited by 8
Comparison of Two Different Treat-and-Extend Protocols with Aflibercept in Wet Age-Related Macular Degeneration: Two-Year Results
Taipale, C., Lindholm, J., Kaarniranta, K., & Tuuminen, R. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01312-2 · Cited by 9
Rhegmatogenous Retinal Detachment after Intravitreal Injection
Brown, K., Yannuzzi, N. A., Smiddy, W. E., Gregori, N. Z., Berrocal, A. M., Haddock, L. J., Schwartz, S. G., Lee, W., Sridhar, J. S., Wu, D. M., et al. (2020) · Ophthalmology Retina · doi:10.1016/j.oret.2020.07.007 · Cited by 10
Influence of unilateral intravitreal bevacizumab injection on the incidence of symptomatic choroidal neovascularization in the fellow eye in patients with neovascular age‑related macular degeneration (Review)
Brănişteanu, D. C., Branisteanu, D. E., Feraru, C., Branisteanu, C., Moraru, A. D., Zemba, M., & Baltă, F. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9312 · Cited by 8
Statement of the German Ophthalmological Society (DOG), the German Retina Society (GRS), and the Professional Association of German Ophthalmologists (BVA) on anti-VEGF treatment in neovascular age-related macular degeneration
DOG) German Society of Ophthalmology (Deutsche Ophthalmologische Gesellschaft, & RG) German Retina Society (Retinologische Gesellschaft e. V. (2020) · Der Ophthalmologe · doi:10.1007/s00347-020-01188-1 · Cited by 8
Finding the Optimal Treatment Plan for Exudative AMD
Patel, A. V., Barb, S. M., & YOUNG, L. H. Y. (2015) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000080 · Cited by 8
“At 2 years, the treatment regimen comparison was inconclusive in IVAN.19 Overall, these studies show evidence that individualized treatment, when used in combination with frequent follow-up, is a viable alternative to the traditional fixed monthly treatments used in the ANCHOR and MARINA trials.”
Result
Ophthalmic Statistics Note 4: analysing data from randomised controlled trials with baseline and follow-up measurements
Nash, R. L., Bunce, C., Freemantle, N., Doré, C. J., & Rogers, C. A. (2014) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2014-305614 · Cited by 8
Self-citation
Impact of methylenetetrahydrofolate reductase C677T polymorphism on the efficacy of photodynamic therapy in patients with neovascular age-related macular degeneration
Parmeggiani, F., Gallenga, C. E., Costagliola, C., Semeraro, F., Romano, M. R., Dell’Omo, R., Russo, A., De Nadai, K., Gemmati, D., D’Angelo, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38919-7 · Cited by 7
Nanomaterial-Based Anti-Angiogenic Gene Therapy for Retinal Neovascular Diseases: Mechanistic Insights and Preclinical Advances
Zeng, L., Wei, Y., Qiu, Y., Bi, R., Peng, H., Hu, B., & Li, Y. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s521960 · Cited by 7
Exploitation of enhanced prime editing for blocking aberrant angiogenesis
Huang, X., Wu, W., Qi, H., Yan, X., Dong, L., Yang, Y., Zhang, Q., Ma, G., Zhang, G., & Lei, H. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.07.006 · Cited by 9
The role of Aflibercept in the management of age-related macular degeneration
Hassan, M., Afridi, R., Sadiq, M. A., Soliman, M. K., Agarwal, A. K., Sepah, Y. J., Diana, V., & Nguyen, Q. D. (2016) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2016.1167182 · Cited by 7
“analyzed.[35] The pooled data analysis for BCVA supported the outcome that BVZ was non-inferior to RBZ, even if one adheres to the strict non-inferiority criterion of the IVAN”
BackgroundInfluential
Effect of ARMS2 gene polymorphism on intravitreal ranibizumab treatment for neovascular age-related macular degeneration
Bardak, H., Bardak, Y., Erçalık, Y., Kumral, E. T., İmamoğlu, S., Günay, M., Özbaş, H., & Bağcı, Ö. (2016) · Genetics and Molecular Research · doi:10.4238/gmr15049164 · Cited by 7
Analyse des Versorgungsmodells „Portal“ – Untersuchung der Ergebnisqualität der IVOM-Therapie im Hinblick auf Latenzzeiten bei exsudativer AMD
Rothaus, K., Farecki, M., Mussinghoff, P., Faatz, H., Spital, G., Pauleikhoff, D., & Lommatzsch, A. P. (2019) · Klinische Monatsblätter für Augenheilkunde · doi:10.1055/a-0982-5294 · Cited by 7
“Hierbei ist gegenwärtig noch der OCT-Befund (OCT: optische Kohärenztomografie) hinsichtlich intraretinaler und subretinaler Flüssigkeit das entscheidende Aktivitätskriterium, denn in allen Zulassungs- und Interventionsstudien korreliert diese morphologische Veränderung mit der Funktion [3,6–8].”
BackgroundInfluential
Macular atrophy development in neovascular age-related macular degeneration during first year of treatment: Incidence and risk factors
Oliveira, M., Farinha, C., Rodrigues, T. M., Martins, A., Cachulo, M. L., Marques, J. P., Pires, I., & da Silva, R. M. (2020) · European Journal of Ophthalmology · doi:10.1177/1120672120908718 · Cited by 7
Clinical outcomes of 1 + PRN and 3 + Q3M regimens of intravitreal conbercept injection for exudative age-related macular degeneration
Gao, L., Liu, J., Zhang, P., Ma, J., & Wang, H. (2020) · Scientific Reports · doi:10.1038/s41598-020-65000-5 · Cited by 7
Patterns and Predictors of Successful Treatment Discontinuation in Retinal Vein Occlusions With Macular Edema in the Real World
Lo, T., Lent-Schochet, D., Luu, K.-Y., Kuriyan, A. E., Weiss, M. Y., Rachitskaya, A. V., Singh, R. P., Wai, K. M., Campbell, J. P., Gupta, K., et al. (2021) · Ophthalmic surgery, lasers & imaging retina · doi:10.3928/23258160-20210201-05 · Cited by 7
Retrospective analysis of OCT parameters after intravitreal anti-VEGF inhibitors in neovascular AMD patients in a real-world setting
Lüke, J. N., Alquoqa, H., Alsamman, A., Aljabary, B., Schaub, F., & Heindl, L. M. (2022) · International Ophthalmology · doi:10.1007/s10792-022-02383-6 · Cited by 7
“This implies only a temporary improvement in visual acuity despite response to anti-VEGF therapy, corresponding to randomized controlled studies ANCHOR, IVAN, MARINA and CATT [6, 7, 18].”
Method
Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration
Parmeggiani, F., Costagliola, C., Semeraro, F., Romano, M. R., Rinaldi, M., Gallenga, C. E., Serino, M. L., Incorvaia, C., D’Angelo, S., Nadai, K. D., et al. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160819796 · Cited by 7
“, monthly or as-needed intravitreal administration of anti-VEGF drugs) [12,13,18–22].”
Background
Ophthalmic statistics note 2: absence of evidence is not evidence of absence
Bunce, C., Patel, K., Xing, W., Freemantle, N., Doré, C. J., & On behalf of the Ophthalmic Statistics Group (2014) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2013-304811 · Cited by 7
Generic and disease-specific estimates of quality of life in macular degeneration: mapping the MacDQoL onto the EQ-5D-3L
Dixon, P., Dakin, H., & Wordsworth, S. (2015) · Quality of Life Research · doi:10.1007/s11136-015-1145-x · Cited by 7
“The data were derived from the IVAN trial [13, 14], a UK factorial randomised controlled trial which assessed ranibizumab versus bevacizumab for the treatment of macular degeneration.”
Method
The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease
Taylor, J., Scott, L. J., Rogers, C. A., Muldrew, A., O’Reilly, D., Wordsworth, S., Mills, N., Hogg, R. E., Violato, M., Harding, S. P., et al. (2015) · Eye · doi:10.1038/eye.2015.170 · Cited by 7
Self-citation
Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration
Hu, S., & Koevary, S. B. (2016) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2015.0111 · Cited by 7
Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes
Warwick, A., Leaver, H., Lotery, A. J., & Goverdhan, S. (2016) · International Journal of Ophthalmology · doi:10.18240/ijo.2016.08.12 · Cited by 7
“Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis in neovascular AMD (nvAMD) and monthly intravitreal injections of the anti-VEGF therapies ranibizumab and bevacizumab have shown improved visual outcomes with similar efficacy [2, 3].”
Self-citation
Fluorescein Angiography Does Not Alter the Initial Clinical Management of Choroidal Neovascularization in Age-Related Macular Degeneration
Parekh, P. K., Folk, J. C., Gupta, P., Russell, S. R., Sohn, E. H., & Abràmoff, M. D. (2018) · Ophthalmology Retina · doi:10.1016/j.oret.2018.01.002 · Cited by 7
“(3-5) However, FFA typically requires placement of an intravenous catheter, dedicated equipment, highly trained operators, additional time, and carries a spectrum of risk, ranging from mild (i.”
Background
Characteristics of Eyes With Good Visual Acuity at 5 Years After Initiation of Treatment for Age-Related Macular Degeneration but Not Receiving Treatment From Years 3 to 5
Scoles, D., Ying, G., Pan, W., Hua, P., Grunwald, J. E., Daniel, E., Jaffe, G. J., Toth, C. A., Martin, D. F., & Maguire, M. G. (2020) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2019.5831 · Cited by 7
Long-Term Visual/Anatomic Outcome in Patients with Fovea-Involving Fibrovascular Pigment Epithelium Detachment Presenting Choroidal Neovascularization on Optical Coherence Tomography Angiography
Kim, K. T., Lee, H., Kim, J. Y., Lee, S., Chae, J. B., & Kim, D. Y. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061863 · Cited by 7
“reported that new geographic atrophy was detected significantly more often during follow-up in participants undergoing a monthly treatment regimen than other regimens [34].”
Background
SINGLE INJECTION RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN PATIENTS WITH WET AGE-RELATED MACULAR DEGENERATION
Bilgic, A., Kodjikian, L., Mathis, T., Sudhalkar, A. A., Vasavada, S. A., & Bhojwani, D. (2021) · Retina · doi:10.1097/iae.0000000000003106 · Cited by 7
RETROSPECTIVE EFFICACY AND SAFETY ANALYSIS OF ZYBEV (BIOSIMILAR OF BEVACIZUMAB) USE AT TERTIARY EYE CARE CENTRES IN INDIA: SPECTRA TRIAL.
Warudkar, S. (2018) · International Journal of Advanced Research · doi:10.21474/ijar01/6234 · Cited by 7
A 5-Year Analysis of Physician-Industry Interactions, Physician Gender, and Anti-VEGF Use in US Ophthalmologists
Watane, A., Kalavar, M., Patel, M. M., Yannuzzi, N. A., Vanner, E. A., Kuriyan, A. E., & Sridhar, J. S. (2021) · Seminars in Ophthalmology · doi:10.1080/08820538.2021.1922710 · Cited by 7
Translational public health care perspective: Intravitreal treatment of neovascular age‐related macular degeneration has revolutionized clinical ophthalmology
Bloch, S. B., & Larsen, M. (2015) · Acta Ophthalmologica · doi:10.1111/aos.12680 · Cited by 7
“…regimen guided by optical coherence tomography in general show poorer efficacy than in clinical trials, which can largely be attributed a lower injection frequency (Bandukwala et al. 2010; Martin et al. 2012; Chakravarthy et al. 2013; Cohen et al. 2013; Finger et al. 2013; Asten et al. 2014).”
Background
The impact of disease activity on 5 year outcomes in patients undergoing treatment for neovascular age related macular degeneration
Chong Teo, K. Y., Nguyen, V., Gemmy Cheung, C. M., Arnold, J., Chen, F. K., Barthelmes, D., & Gillies, M. C. (2021) · Zurich Open Repository and Archive (University of Zurich) · doi:10.1097/iae.0000000000003267 · Cited by 6
“02 VA #35 letters, n (%) 82 (20) 78 (21) 105 (24) 0.”
Prime Editing of Vascular Endothelial Growth Factor Receptor 2 Attenuates Angiogenesis In Vitro
Ma, G., Qi, H., Deng, H., Dong, L., Zhang, Q., Ma, J., Yang, Y., Yan, X., Duan, Y., & Lei, H. (2024) · The CRISPR Journal · doi:10.1089/crispr.2024.0019 · Cited by 6
Fight Retinal Blindness SPAIN. Report 3: clinical outcomes of vascular endothelial growth factor inhibitors in low vision eyes with neovascular age-related macular degeneration. A national database study
Puzo, M., Calvo-Perez, P., Bartol-Puyal, F. D. A., Sánchez‐Monroy, J., Martín, R., Parrado‐Carrillo, A., Moll‐Udina, A., Bernal-Morales, C., Sánchez-Vela, L., Sararols, L., et al. (2024) · Eye · doi:10.1038/s41433-024-03322-8 · Cited by 6
Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687
Vanhove, M., Wagner, J.-M., Noppen, B., Jonckx, B., Vermassen, E., & Stitt, A. W. (2021) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-021-09774-9 · Cited by 6
Prevalence and Progression of Macular Atrophy in Eyes with Neovascular Age-Related Macular Degeneration in the Phase 2 Ladder Trial of the Port Delivery System with Ranibizumab
Jaffe, G. J., Cameron, B., Kardatzke, D. R., Ives, J. A. L., Barteselli, G., & Gune, S. (2022) · Ophthalmology Retina · doi:10.1016/j.oret.2022.04.006 · Cited by 6
Treatment of age‐related macular degeneration with aflibercept using a treat, extend and fixed protocol; A 4‐year study of treatment outcomes, durability, safety and quality of life (An extension to the MATE randomised controlled trial)
Airody, A., Baseler, H. A., Seymour, J., Allgar, V. L., Mukherjee, R., Downey, L., Dhar‐Munshi, S., Mahmood, S., Balaskas, K., Empeslidis, T., et al. (2023) · Acta Ophthalmologica · doi:10.1111/aos.15774 · Cited by 6
“Patient-reported outcome measures (PROMs) were assessed using the Macular Disease dependent Quality of Life (MacDQoL) and the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ).”
MethodResultInfluential
Sustained Suppression of VEGF for Treatment of Retinal and Choroidal Vascular Diseases
Campochiaro, P. A. (2025) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2025.04.032 · Cited by 6
Pro-re-nata-anti-VEGF-Behandlungsergebnisse bei neovaskulärer altersabhängiger Makuladegeneration in der klinischen Routineversorgung: Vergleich von Einzel- mit 3er-Injektionen
Wintergerst, M. W. M., Larsen, P. P., Heimes, B., Pauleikhoff, D., Holz, F. G., & Finger, R. P. (2018) · Der Ophthalmologe · doi:10.1007/s00347-018-0747-4 · Cited by 5
Applications of Artificial Intelligence for the Diagnosis, Prognosis, and Treatment of Age-related Macular Degeneration
CAI, L. Z., Hinkle, J. W., Arias, D. E., Gorniak, R., Lakhani, P. C., Flanders, A. E., & Kuriyan, A. E. (2020) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000334 · Cited by 6
Early detection of neovascular age-related macular degeneration: an economic evaluation based on data from the EDNA study
Hernández, R. A., Kennedy, C., Banister, K., Goulão, B., Cook, J. A., Sivaprasad, S., Hogg, R. E., Azuara‐Blanco, A., Heimann, H., Dimitrova, M., et al. (2021) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2021-319506 · Cited by 6
“Postloading phase changes in VA were informed primarily by data from the ranibizumab arm of the UK based IVAN trial.(10,11) Following the approach described by Claxton et al.”
MethodSelf-citation
Cost impact of different treatment regimens of brolucizumab in neovascular age-related macular degeneration: A budget impact analysis
Siddiqui, Z. A., Dhumal, T., Patel, J. S., LeMasters, T., Almony, A., & Kamal, K. M. (2022) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2022.28.12.1350 · Cited by 6
Towards a population pharmacokinetic/pharmacodynamic model of anti-VEGF therapy in patients with age-related macular degeneration
del Amo, E. M., Bishop, P. N., Godia, P., & Aarons, L. J. (2023) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2023.05.007 · Cited by 6

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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