Aflibercept Likely to Improve Severity, Complications of Nonproliferative Diabetic Retinopathy

Findings of the PANORAMA randomized clinical trial show that when patients with severe nonproliferative diabetic retinopathy were treated with intravitreal aflibercept, severity improved over 100 weeks and the likelihood of vision-threatening complications significantly reduced.

Intravitreal injections of aflibercept may significantly reduce the severity and likelihood of vision-threatening complications in patients with severe nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME), according to study findings published in JAMA Ophthalmology.

In the management of diabetic retinopathy (DR), the leading cause of blindness globally, there are 13 distinct categories on the Diabetic Retinopathy Severity Scale (DRSS) that range from NPDR to proliferative DR (PDR).

Although increasing NPDR severity is associated with a greater risk of progression to PDR and vision loss, the researchers note that current DR treatment guidelines recommend a reactive approach in which treatment is administered only when center-involved DME (CI-DME) and/or PDR develop.

“Once PDR has developed, retinal damage from fibrosis and contraction may not be reversible, even with intervention, and can be associated with permanent vision loss,” said the study authors. “Subsequent treatment with panretinal photocoagulation leads to visual field loss because the procedure is inherently destructive.”

In the Study of the Efficacy and Safety of Intravitreal Aflibercept for the Improvement of Moderately Severe to Severe NPDR (PANORAMA) double-masked 100-week randomized clinical trial, the researchers sought to evaluate the efficacy of a preventive, proactive treatment approach comparing intravitreal aflibercept injections with sham injections in eyes with moderately severe to severe NPDR and no DME.

Adult patients with DRSS level 47 or 53 with no DME and best-corrected visual acuity of 20/40 or better were included in the study (N = 402; mean [SD] age, 55.7 [10.5] years; 225 [56.0%] were male; 310 [77.1%] were White). Participants were split into 3 groups:

  • Aflibercept 2q16 group included 135 participants administered 2-mg intravitreal injections of aflibercept every 16 weeks after 3 initial monthly doses and one 8-week interval
  • Aflibercept 2q8/pro re nata (PRN), or as-needed, group included 134 participants administered 2-mg intravitreal injections of aflibercept every 8 weeks after 5 initial monthly doses, with PRN dosing beginning at week 56
  • Control group included 133 participants administered sham injections

The primary outcomes assessed were proportions of eyes with a 2-step or greater improvement in DRSS level, vision-threatening complications, and center-involved DME from baseline to weeks 24, 52, and 100. One eye was evaluated per participant.

In the study findings, combined data of both aflibercept groups at 24 weeks were associated with a 2-step or greater improvement in DRSS level in 157 of 269 eyes (58.4%) vs 8 of 133 eyes (6.0%) in the control group (adjusted difference, 52.3%; 95% CI, 45.2%-59.5%; P < .001).

At 52 weeks, the severity of NPDR improved further in the intervention groups, with 88 of 135 eyes (65.2%) in the aflibercept 2q16 group (adjusted difference, 50.1%; 95% CI, 40.1%-60.1%) and 107 of 134 eyes (79.9%) in the aflibercept 2q8/PRN group (adjusted difference, 64.8%; 95% CI, 55.8%-73.9%) exhibiting a 2-step or greater improvement in DRSS level compared with 20 of 133 eyes (15.0%) in the control group (P < .001 for both comparisons).

Furthermore, development of vision-threatening complications and/or center-involved DME were reported in fewer eyes treated with aflibercept (22 of 135 eyes [16.3%] in the 2q16 group [adjusted difference, −34.2%; 95% CI, −44.6% to −23.8%] and 25 of 134 eyes [18.7%] in the 2q8/PRN group [adjusted difference, −31.7%; 95% CI, −42.5% to −20.9%]) compared with the control group through week 100 (67 of 133 eyes [50.4%]; P < .001 for both comparisons).

“NPDR represents a potential window of opportunity to slow disease progression, thereby preventing the development of potentially irreversible damage that may lead to vision loss and have a meaningful impact on quality of life,” concluded the study authors. “Outcomes on the DRSS between year 1 and 2 emphasize the need for ongoing vascular endothelial growth factor suppression and adherence.”


Brown DM, Wykoff CC, Boyer D, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy. JAMA Ophthalmol. Published online August 5, 2021. doi:10.1001/jamaophthalmol.2021.2809

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