Delaying Diabetic Macular Edema Therapy Results in Greater Acuity Loss

Fluorescence angiogram of retina showing severe case of diabetic retinopathy, associated with diabetes mellitus. The angiogram shows distinct, multiple microaneurysms and hemorrhages
Analysis of VIVID/VISTA and PANORAMA shows early treatment is better for diabetic macular edema and nonproliferative retinopathy.

This article is part of Ophthalmology Advisor’s conference coverage from the 2021 meeting of The Association for Research in Vision and Ophthalmology (ARVO), held virtually from May 1 to 7, 2021. The team at Ophthalmology Advisor will be reporting on a variety of the research presented by the eye and vision experts at ARVO. Check back for more from the ARVO 2021 Meeting.


The 3 most important words for treating diabetic retinal disease may well be early, early, and early. The impact of therapy regimens for diabetic macular edema (DME) in the VISTA ( NCT01363440) and VIVID ( Identifier: NCT01331681) clinical trials, and treatment protocols for non-proliferative diabetic retinopathy (NPDR) in phase 3 PANORAMA was analyzed by Carolyn Pan, MD and outlined in a poster presentation at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting, held virtually from May 1 to 7, 2021.

In VIVID and VISTA (eyes; n=872), participants with DME who received delayed anti-vascular endothelial growth factor (VEGF) therapy attained comparable central subfield thickness (CST) outcomes, but did not reach similar 100-week best-corrected visual acuity (BCVA) as those who obtained intravitreal injections at week 1.

Dr. Pan explained that when evaluating treatment effectiveness, there is a difference between the impact on foveal thickness and visual acuity. “The CST is a poor surrogate for retinal function, as retina with loss of neurons and/or glial cells could have normal thickness if there is extracellular fluid in the retina, or there could be disruptions of the retinal anatomic connections but (still) maintain normal thickness,” explained Dr. Pan, a vitreoretinal surgeon and clinical associate professor at Stanford University. “However in both cases, the retinal function is diminished and thus visual acuity is diminished.”

In VIVID and VISTA, outcomes for participants who underwent intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), and those who received IAI every 8 weeks (2q8) after starting with 5 monthly injections, were compared with results for individuals who obtained laser control. Mean BCVA in the 2q4 and 2q8 groups was 59.8 and 59.1 letters at baseline, respectively; and 71.5 and 70.2 letters by week 100. For laser with rescue, BCVA was 59.5 letters at baseline, 49.0 at rescue initiation, and 57.9 at week 100. Mean CST in μm for the 2q4 and 2q8 groups was 493.1 and 497.6 at baseline, and 289.4 and 290.1 at week 100. For laser with rescue, CST was 537.5 μm at baseline, 538.5 at rescue initiation, and 272.9 by study’s end.

PANORAMA participants ( Identifier: NCT02718326) (N=402) with moderately severe to severe NPDR without DME were randomized into 3 groups; those who, after a loading phase, received IAI 2 mg every 16 weeks (2q16), or obtained IAI every 8 weeks (2q8/PRN); or control individuals who underwent sham therapy. All patients were able to have rescue treatment for PDR/anterior segment neovascularization (ASNV), or center-involved DME (CI-DME). In the 2q16 and 2q8/PRN groups, 3.0% and 3.7% of individuals, respectively, met rescue criteria for PDR/ASNV, and in the sham set, 14.3% needed rescue. In the 2q16 and 2q8/PRN groups, 7.4% and 8.2% met rescue criteria for CI-DME, and 29.3% in the sham group were rescued during the 100-week trial.

The 2q16 group in PANORAMA displayed a 77% risk reduction for progression to PDR or ASNV at study’s end. “These analyses from VIVID/VISTA and PANORAMA suggest earlier treatment could be clinically beneficial in both DME and NPDR patients,” according to the analysis.

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Pan CK. Treatment for diabetic retinal disease: impact of early/prophylactic treatment. Presented at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting; May 1-7, 2021. Poster 3530280.