Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical Trial

Abstract

Importance: Studies have established the efficacy and safety of aflibercept for the treatment of macular edema due to central retinal vein occlusion. Bevacizumab is used off-label to treat this condition despite the absence of supporting data.

Objective: To investigate whether bevacizumab is noninferior to aflibercept for the treatment of macular edema secondary to central retinal or hemiretinal vein occlusion.

Design, setting, and participants: The SCORE2 randomized noninferiority clinical trial was conducted at 66 private practice or academic centers in the United States, and included 362 patients with macular edema due to central retinal or hemiretinal vein occlusion who were randomized 1:1 to receive aflibercept or bevacizumab. The first participant was randomized on September 17, 2014, and the last month 6 visit occurred on May 6, 2016. Analyses included data available as of December 30, 2016.

Interventions: Eyes were randomized to receive intravitreal injection of bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg; n = 180) every 4 weeks through month 6.

Main outcomes and measures: The primary outcome was mean change in visual acuity (VA) letter score (VALS) from the randomization visit to the 6-month follow-up visit, based on the best-corrected electronic Early Treatment Diabetic Retinopathy Study VALS (scores range from 0-100; higher scores indicate better VA). The noninferiority margin was 5 letters, and statistical testing for noninferiority was based on a 1-sided 97.5% confidence interval.

Results: Among 362 randomized participants (mean [SD] age, 69 [12] years; 157 [43.4%] women; mean [SD] VALS at baseline, 50.3 [15.2] [approximate Snellen VA 20/100]), 348 (96.1%) completed the month 6 follow-up visit. At month 6, the mean VALS was 69.3 (a mean increase from baseline of 18.6) in the bevacizumab group and 69.3 (a mean increase from baseline of 18.9) in the aflibercept group (model-based estimate of between-group difference, -0.14; 97.5% CI, -3.07 to ∞; P = .001 for noninferiority), meeting criteria for noninferiority. Ocular adverse events in the aflibercept group included 4 participants with intraocular pressure (IOP) more than 10 mm Hg greater than baseline; ocular adverse events in the bevacizumab group included 1 participant with endophthalmitis (culture negative), 9 with IOP more than 10 mm Hg greater than baseline, 2 with IOP higher than 35 mm Hg, and 1 with angle-closure glaucoma not attributed to the study drug or procedure.

Conclusions and relevance: Among patients with macular edema due to central retinal or hemiretinal vein occlusion, intravitreal bevacizumab was noninferior to aflibercept with respect to visual acuity after 6 months of treatment.

Figure 1.. Flowchart of Participant Progress in the SCORE2 Trial

^aPatients may be ineligible at screening for multiple reasons; thus, the number of reasons for ineligibility may not sum to the number of ineligible patients. ^bEligibility criteria included central retinal thickness on spectral-domain optical coherence tomography (SD-OCT), which was defined as central subfield thickness of 300 µm or greater if measured with a Carl Zeiss Meditec Cirrus OCT machine or 320 µm or greater if measured with a Heidelberg Spectralis OCT machine. ^cFor example, chronic alcoholism or drug abuse, personality disorder, or use of major tranquilizers, indicating difficulty in long-term follow-up and likelihood of survival of less than 12 months.

Figure 2.. Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score at Baseline and Monthly Through Month 6

The center horizontal line of each box indicates the median; circle, mean; and top and bottom borders of each box, 75th and 25th percentiles, respectively. The whiskers extend to the minimum observation above the lower fence and maximum observation below the upper fence, which are defined as 1.5 times the interquartile range below the 25th percentile and above the 75th percentile, respectively. The outliers (squares) mark any observation below the lower fence or above the upper fence.

Figure 3.. Spectral-Domain Optical Coherence Tomography Central Subfield Thickness at Baseline and Monthly Through Month 6

The center horizontal line of each box indicates the median; circle, mean; and top and bottom borders of each box, 75th and 25th percentiles, respectively. The whiskers extend to the minimum observation above the lower fence and maximum observation below the upper fence, which are defined as 1.5 times the interquartile range below the 25th percentile and above the 75th percentile, respectively. The outliers (squares) mark any observation below the lower fence or above the upper fence.

Figure 4.. Color Fundus Photograph and Optical Coherence Tomogram of the Left Eye at Baseline and Month 6 in a Representative SCORE2 Participant With a Central Retinal Vein Occlusion

At baseline, the color fundus photograph of the central 30° of the retina showed extensive retinal hemorrhages and dilated retinal veins. The optic nerve was not visible because of retinal edema and blood. Retinal edema was present throughout the retina and is best seen on optical coherence tomography (OCT), which provides a cross-sectional image of the retina. The OCT scan shown here was taken through the center of the retina. The participant’s visual acuity was 20/400 at baseline. At month 6, the color fundus photograph of the retina in the same participant showed nearly complete resolution of intraretinal blood after receiving monthly injections of aflibercept for 6 months. The optic nerve was visible and appeared normal. The OCT scan showed that retinal edema resolved and the fovea returned to its normal contour. At month 6, the participant’s visual acuity improved to 20/40.