VISTA subanalysis: Macular RNP and clinical outcomes

August 11, 2020
Michelle Dalton, ELS
Michelle Dalton, ELS

Reductions in macular retinal nonperfusion after anti-VEGF treatment with aflibercept are correlated with improvements in BCVA and central retinal thickness in patients with DR/DME, according to a post-hoc analysis of the VISTA dataset, said Charles C. Wykoff, MD, PhD, during ARVO 2020.

Reductions in macular retinal nonperfusion after anti-vascular endothelial growth factor (VEGF) treatment with aflibercept are correlated with improvements in best-corrected visual acuity (BCVA) and central retinal thickness in patients with diabetic retinopathy and diabetic macular edema (DR/DME), according to a post-hoc analysis of the VISTA dataset, said Charles C. Wykoff, MD, PhD, Retina Consultants of Houston, during ARVO 2020.

“At its core, DR is a progressive retinal vascular disease. One of the benefits of anti-VEGF therapy may be their effect on the retinal vasculature itself,” he said.

Related: ASRS 2020: Protocol T Extension Study shows long-term visual declines in DME eyes


VISTA/VIVID were phase III trials that compared aflibercept to macular laser for 2 years in patients with DME, with a total trial duration of 3 years.1

“When considering retinal nonperfusion grossly at the quadrant level, aflibercept treatment was associated with less worsening and more improvement in nonperfusion compared to sham treatment” in a prior VISTA sub-analysis,2 Dr. Wykoff said.

The goal of this VISTA post hoc analysis was to “better understand changes in retinal nonperfusion by quantifying macular nonperfusion area in mm2 at baseline and through week 100,” Dr. Wykoff said.

Other objectives included assessing the relationship between changes from baseline and RNP area at week 100 for BCVA, central subfield thickness (CST), and Diabetic Retinopathy Severity Scale (DRSS) score, as well as the impact of baseline retinal nonperfusion area on the development of proliferative diabetic retinopathy (PDR).

Related: Bowtie artifacts: Clinical biomarkers for center-Involving DME?

Study design
Of the 466 patients enrolled into VISTA, 178 patients met the inclusion criteria for the subanalysis, which included fluorescein angiography at baseline and weeks 52 and 100,with quantifiable retinal nonperfusion at baseline as determined by a masked reading center.

These patients were randomized to 1 of 3 arms in the phase 3 trial: aflibercept 2 mg dosing every 4 weeks (2q4, 60 patients) or every 8 weeks (2q8, 55 patients) following 5 monthly doses or laser treatment (63 patients).

Demographics were similar between arms. Patients had a mean age of 60, mean BMI of 32, and mean HbA1c of 7.7.

“Ocular characteristics appeared well balanced between the arms at baseline with about 50% of these eyes having moderately severe to severe non-proliferative diabetic retinopathy (NPDR)at baseline or DRSS levels 47 and 53,” Dr. Wykoff said.

Related: ASRS 2020: Diabetic retinopathy progression in anti-VEGF versus FA implant

Results
At baseline, mean areas of retinal nonperfusion were small, at 1.7 mm2, 1.5 mm2, and 1.5 mm2 in the 2q4, 2q8, and laser groups, respectively.

All arms experienced small decreases in retinal nonperfusion from baseline to week 100 (-0.7 mm2, -0.6 mm2, and -0.2 mm2, respectively) as determined by the masked reading center, but the differences between the groups were not statistically significant.

However, within the treatment groups themselves, “we see that among both aflibercept-treated populations … there was a statistically significant decrease in [the] nonperfusion area from baseline to week 100,” Dr. Wykoff said. “Among the laser-treated patients … while there was a numerical decrease in RNP from baseline to week 100, this change was not statistically significant.”

In the aflibercept groups, reductions in RNP from baseline were associated with changes in BCVA (r= -0.6 2q4 and -0.5 2q8, P < 0.05) and CRT (r = 0.7 2q4 and 0.4 2q8, P < 0.05), but not with change in DRSS score.

Related: Central subfield thickness only partially responsible for changes in acuity

“As BCVA increased, the retinal nonperfusion area decreased among aflibercept-treated eyes. Similarly, for CST, there was a moderate positive correlation. As CST decreased, retinal nonperfusion decreased among aflibercept-treated eyes,” Dr. Wykoff explained. “There were no correlations with changes in retinal nonperfusion and DRSS, and there were no significant correlations identified among the laser-treated population. Of note, all of these analyses have considered just the two variables in isolation without correcting for any of the other variables among the populations.”

Importantly, PDR events were higher in the laser arm than the combined aflibercept populations at 14% vs 2.8%, respectively.

“The extent of baseline retinal nonperfusion appeared to be associated with an increased risk of progression to PDR, particularly among laser treated patients,” Dr. Wykoff said. DR is a common cause of irreversible visual loss, and slowing the core pathophysiologic process of progressive vascular loss is a key goal to consider in clinical practice, he said.

Read more by Michelle Dalton

References
1.Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies. Ophthalmology 2016;123(11):2376-85.

2.Wykoff CC, Shah C, Dhoot D, et al. Longitudinal Retinal Perfusion Status in Eyes with Diabetic Macular Edema Receiving Intravitreal Aflibercept or Laser in VISTA Study. Ophthalmology 2019;126:1171-1180.