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JAMA Ophthalmol. 2019 Apr 1;137(4):372-379. doi: 10.1001/jamaophthalmol.2018.6776.

Effect of Ranibizumab and Aflibercept on Best-Corrected Visual Acuity in Treat-and-Extend for Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Author information

Macular Research Group, Save Sight Institute, The University of Sydney, Sydney Eye Hospital, Sydney, New South Wales, Australia.
Retina Associates, Chatswood, New South Wales, Australia.
Marsden Eye Specialists, Parramatta, New South Wales, Australia.
Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital and Ophthalmology, Department of Surgery, University of Melbourne, Victoria, Australia.
Department Ophthalmology, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
Outlook Eye Specialists, Southport, Queensland, Australia.
Healthcare Professionals Group Pty Ltd, Sydney, New South Wales, Australia.
Center for Ophthalmology and Visual Science, Lions Eye Institute, The University of Western Australia, Perth, Western Australia, Australia.



To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD).


To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial.

Design, Setting, and Participants:

The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments.


Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase.

Main Outcomes and Measures:

Mean change in BCVA and the number of injections from baseline to month 12.


Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; Pā€‰=ā€‰.06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; Pā€‰=ā€‰.86).

Conclusions and Relevance:

Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified.

Trial Registration:

Clinicaltrials.Gov identifier: NCT02130024.

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