Moderate-to-Severe NPDR Confers Greatest Risk of Progression to Vision-threatening Disease

A new study aims to fill a significant gap in existing literature regarding the natural evolution of diabetic retinopathy (DR), specifically seeking to determine how baseline disease severity affects a patient’s risk of progressing to vision-threatening forms, including proliferative DR (PDR) and diabetic macular edema (DME). To achieve this, the research team analyzed a large database of fundus photos from patients screened at primary care centers across the US, finding that those with moderate-to-severe nonproliferative DR at baseline were more likely to develop PDR or DME.The study employed a prospective, longitudinal, non-interventional cohort design, including patients older than 18 years who underwent DR screening in either eye between 1999 and 2016. The severity of DR was classified according to the ETDRS Diabetic Retinopathy Severity Scale (DRSS).Among 41,977 eyes evaluated, the rate of progression to at least a two-step worsening in DR increased from 2.7% at two years to 9.6% by the fifth year. Most notably, eyes classified as having moderate-to-severe NPDR at baseline—indicated by a DRSS score between 43 and 53—showed an alarmingly high progression rate, with 36.5% of these eyes progressing to either PDR or DME over five years.  While baseline DR severity was linked to disease progression rates in this study, its authors also found distinct subsets of patients where five-year progression risk was independent of baseline DRSS, including patients with the type 1 form of diabetes (see chart), suggesting that other individual factors likely play a role. Photo: Habte-Asres HH, et al. Diabetic Medicine. October 7, 2025. Click image to enlarge. The study also identified three distinct DR clinical subtypes where five-year progression to PDR and/or DME was not driven by baseline severity. One group of patients primarily progressed to DME, with 1.24% of eyes developing this condition by the fifth year, while another subset progressed solely to PDR at a lower rate of 0.49%. Only 0.10% of the cohort progressed to both PDR and DME. These findings suggest that other individual factors beyond baseline DR severity may contribute to the progression to severe disease forms, which the authors suggested should be explored in future research. For advice on how to manage a newly diagnosed DR patient, see this feature. Diabetes type was also found to influence DR progression, as reported in prior studies; specifically, a higher proportion of patients with type 1 diabetes exhibited DR worsening by ≥two steps compared to those with type 2 diabetes (19% vs. 13% at five years). While comparisons between these two populations are limited, given that over 90% of patients with diabetes in this study had type 2, the researchers conveyed that this observation “aligns with the real-world prevalence of these subtypes and highlights to physicians that patients with type 1 diabetes mellitus may require additional vision management, as they may be more at risk for vision-threatening DR.”While screening guidelines are established for patients with diabetes to help prevent, delay and manage the disease, the researchers emphasized that it’s important for clinicians to remember that DR progression will still occur in some patients. “Our real-world findings may help educate physicians about DR progression patterns and highlight the importance of early screening, which could facilitate timely diagnosis and physician implementation of strategies to delay progression, thus improving quality of life for patients,” they wrote.Click here for the journal source. Lalwani G, Wykoff CC, Briggs J, et al. Progression of diabetic retinopathy in a longitudinal real-world study of patients in primary care. BMC Ophthalmol. 2025;25:547. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.