Diabetic retinopathy (DR) is the major cause of
visual impairment and
blindness in the working-age population. Conventional management for nonproliferative
diabetic retinopathy (NPDR) without diabetic
macular edema (DME) is derived from the findings of the Early Treatment
Diabetic Retinopathy Study (ETDRS). Although the ETDRS protocol basically includes observation, selected cases of severe NPDR may undergo scatter
laser photocoagulation. Post-hoc analysis of recent trials has shown that patients with NPDR receiving intravitreal anti-
vascular endothelial growth factor (anti-
VEGF) for DME would experience improvement in the DR severity scale (DRSS). In addition, recent randomized trials (PANORAMA and Protocol W) have revealed that early intervention with intravitreal
aflibercept in eyes with moderately severe to severe NPDR is associated with significant improvement in DRSS and
reduced vision-threatening complications of DR. Based on recent studies, it seems that the therapeutic approach to NPDR may undergo a substantial change and a paradigm shift toward considering early intervention with the administration of intravitreal anti-
VEGF injections. However, the long-term results and the duration of adherence to anti-
VEGF therapy for eyes with NPDR are not yet defined. It is also not apparent whether improvement in DRSS is a true disease modification. Studies showed that DRSS improvement is not associated with
retinal reperfusion. In addition, DRCR.net Protocol W showed no visual acuity benefit with the early intravitreal
aflibercept injection in moderate to severe NPDR as compared with performing observation plus intravitreal
aflibercept applied only after progression to proliferative DR or vision-impairing DME. The cost-benefit ratio is also a challenge. Herein, we look at different aspects of early anti-
VEGF application and discuss its pros and cons in the process of treating NPDR.