Anti-VEGF therapy has long been the standard of care for patients with diabetic macular edema (DME) caused by diabetic retinopathy (DR). But is treatment being recommended too late? Currently, most DR patients aren’t receiving the potentially sight-saving injections until center-involved DME (CI-DME) and/or proliferative DR (PDR) has already begun to develop. At that point, retinal damage from fibrosis and contraction may be irreversible and result in permanent vision loss. Offering treatment to patients with severe nonproliferative diabetic retinopathy (NPDR) could help prevent progression to DME and PDR and allow more patients to maintain their vision-related quality-of-life functioning.

A randomized 100-week clinical trial study, named PANORAMA, found that treating severe NPDR patients with intravitreal aflibercept injections may decrease vision-threatening complications and center-involved DME. 

DR severity was quantified using the Diabetic Retinopathy Severity Scale (DRSS), which includes 13 categories ranging from NPDR to PDR. The subjects included 402 adults with levels of 47 or 53 on the DRSS, no DME and best-corrected visual acuities of 20/40 or better. They were randomly assigned to the following groups for treatment: 135 to the aflibercept 2q16 group (2mg aflibercept every 16 weeks after three intial monthly doses and one 8-week interval); 134 to the aflibercept 2q8/PRN group (2mg aflibercept every eight weeks after five initial monthly doses in year one and PRN dosing in year two for those with DRSS levels over 35); and 133 to the control group (receiving sham injections).

Researchers observed the following:

  • At week 24, the proportion of eyes with at least a two-step improvement in DRSS level was significantly higher in the combined aflibercept groups vs. the control group (58.4% of eyes vs. 6%).
  • The risk of a two-step or greater worsening in DRSS level was heavily reduced by 89% at week 52 and 81% at week 100 in the aflibercept 2q16 group and by 100% at week 52 and 93% at week 100 in the aflibercept 2q8/PRN group.
  • The development of PDR or CI-DME was reduced among eyes treated with aflibercept compared with sham injections by more than 70% through weeks 52 and 100.

“With continued dosing of intravitreal aflibercept at a fixed interval of every 16 weeks, the proportion of participants with a two-step or greater improvement in DRSS level at week 52 (65.2%) was maintained through week 100 (62.2%),” the authors of the study wrote. “To maintain DRSS improvement and minimize the risk of vision-threatening events, treatment at a fixed frequency (e.g., 3-4 times annually) allows alteration of the natural history of disease progression in this patient population without increasing the management burden.”

The authors conclude by noting that the study’s findings “demonstrated that treatment with aflibercept meaningfully reduced the risk of clinically relevant manifestations of DR and that this benefit was seen with an injection frequency consistent with current practice guidelines.” Look at cases of patients with severe NPDR as potential windows of opportunity to slow disease progression and prevent further vision damage by treating them with consistently dosed intravitreal aflibercept injections.

DM Brown, Wykoff CC, Boyer D, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy. JAMA Ophthalmol. August 5, 2021. [Epub ahead of print].