Intravitreal aflibercept injection showed a high level of ≥2-step improvement in DRSS compared with sham for patients with moderately severe to severe nonproliferative diabetic retinopathy.
Rishi P. Singh, MD
Intravitreal aflibercept (Eylea) injection showed a high level of ≥2-step improvement in diabetic retinopathy severity scale (DRSS) compared with sham for patients with moderately severe to severe nonproliferative diabetic retinopathy (NPDR), according to findings from the phase 3 PANORAMA study presented at the 2019 American Academy of Ophthalmology Annual Meeting.
At week 52 in the study, 79.9% of patients in the aflibercept arm had a ≥2-step improvement from baseline in DRSS compared with 15% of patients receiving a sham. This improvement versus sham was highly statistically significant (P <.0001). Moreover, the onset of this improvement was rapid, with a benefit for aflibercept emerging at day 57.
"PANORAMA is the first large, prospective trial of eyes with moderately severe to severe nonproliferative diabetic retinopathy in patients without diabetic macular edema [DME], since the ETDRS," said lead investigator Rishi P. Singh, MD, from the Cleveland Clinic. "Vision-threatening complications and central-involved-DME occurred in a substantially greater proportion of eyes receiving sham."
The double-masked study enrolled 402 patients across 3 treatment arms. Patients received a sham injection (n = 133) or aflibercept at 2 mg every 16 weeks (n = 135) or every 8 weeks (n = 134). Baseline characteristics were well balanced across arms in the study. The median age of patients was 55.7 years. The mean duration of diabetes was 14.4 years (±9.2), and the HbA1c was 8.5 mmol/mol. The BCVA at baseline was 82.4 letters (20/25) and the central retinal thickness was 247.4 μm. Baseline DRSS was level 47 for 75.1% of patients and level 53 for 24.9%.
For aflibercept at 2 mg every 16 weeks, 65.2% of eyes had a ≥2 step improvement in diabetic retinopathy at week 52. This was similar to the rate seen at week 24, wherein 62.7% of patients had a ≥2-step improvement. Patients received 5.5 injections in this group.
In the aflibercept 2 mg every 8-week group, patients received 8.8 injections at week 52. Through week 52 of the study, cumulative improvements were seen in diabetic retinopathy. In this group, there was a ≥2-step improvement at week 24 for 55.2% of patients. By week 40, 67.9% of patients saw a ≥2-step improvement in DRSS. By week 52, the 79.9% had a ≥2-step improvement.
There was a significant reduction in the area of fluorescein leakage through week 52 in the 2 aflibercept arms compared with no significant change in the sham group. At baseline, in the 16-week group, the leakage area was 20.6 mm2, which declined to 6.2 mm2 at week-52. In the every-8-week group, the baseline was 19.9 mm2, which dropped to 4.0 mm2 at week 52. Reduction in leakage was seen as early as week 12.
Vision threatening complications (VTC) or central involved DME (CI-DME) were significantly reduced with aflibercept. The rate of either VTC or CI-DME was 9.6% and 11.2% in the 8- and 16-week groups for aflibercept compared with 40.6% for sham, representing an approximate 80% reduction in the risk of developing an event over time. These rates were similar for VTC alone and CI-DME alone.
"We can all make pictures look pretty and reduce the number of my grandeur isms and hemorrhages that are present but what effect does that have on visual outcomes, center-involving diabetic macular edema development, developing vision threatening complications from diabetes, and looking at fluorescein and angiography leakage on patients in the study?" Singh said in an interview with the HCPLive Network. "The PANORAMA study was really trying to evaluate those endpoints in much more prospective fashion that's not been done in previous trials."
Through week 52 of the PANORAMA study, Singh noted that there were no new safety signals with aflibercept. At the analysis, there was one serious adverse event (SAEs) of iris neovascularization, and one patient had 2 SAEs, which included a vitreous hemorrhage and reduced visual acuity.
Based on the promising early findings from PANORAMA, in May 2019, the FDA approved aflibercept injection to all stages of diabetic retinopathy. Aflibercept is currently approved for patients with neovascular age-related macular degeneration, DME, and macular edema following retinal vein occlusion.
Rishi P. Singh, MD. Management of High-risk Nonproliferative Diabetic Retinopathy Without Diabetic Macular Edema: Results From PANORAMA. Presented at: 2019 AAO Annual Meeting, San Francisco, CA, October 12-15, 2019.