Usage of UWF-FA May Improve Ability to Predict Disease Worsening in Eyes with NPDR


Ultra-widefield fluorescein angiography allow more accurate risk identification of eyes with non proliferative diabetic retinopathy than baseline severity level alone in new findings.

The presence of ultra wide-field fluorescein angiography (UWF-FA) detected predominantly peripheral lesions (PPLs) was associated with greater risk of worsening disease in eyes with nonproliferative diabetic retinopathy (NPDR).

The greater risk was determined to be independent of the baseline Diabetic Retinopathy Severity Scale (DRSS) score, suggesting peripheral findings on UWF-FA allow more accurate risk identification in eyes with NPDR.

“Thus, among eyes with NPDR, the presence of PPL identified using UWF-FA imaging appears to be a marker for increased risk of disease worsening that is not detectable using standard ETDRS 7-field photography or UWF-color imaging alone,” wrote study author Adam R. Glassman, MS, Jaeb Center for Health Research.

The Study

The DRCR Retina Network Protocol AA evaluated whether the detection of PPL on UWF-color or UWF-FA improves the ability to predict the rate of worsening retinopathy beyond baseline risk.

The prospective observational longitudinal study was conducted at 37 clinical sites in the United States and Canada. Individuals were 18 years or older, had type 1 or type 2 diabetes, and had at least 1 eye with NPDR confirmed on ETDRS modified 7-field grading.

Investigators noted the procedure for the UWF-color imaging included two 200° central images and two 200° steered images obtained and graded for DRSS at a reading center. The score on the DRSS was evaluated on ETDRS 7-field and UWF-color images and PPL presence was determined independently from UWF-color and UWF-FA images.

Primary outcomes as disease worsening as a time-to-event outcome was defined as either worsening by 2 or more steps on the DRSS assessed within the ETDRS fields from the UWF-color images or receipt of DR treatment over 4-years of follow-up.


From February 2015 - December 2015, the study enrolled a total of 388 participants with data analyzed from May 2020 - June 2022. The analysis cohort consisted of 544 study eyes from 367 participants (182 [50%] female participants; median age, 62 years; 68% White) who had ≥1 eye with NPDR on UWF-color that was gradable for PPL.

Among the 544 eyes, PPLs were present in 221 eyes (41%) on UWF-color and 247 (46%) on UWF-FA. The median baseline visual acuity letter score was 86 letters. Over 4 years, treatment for DR or DME was initiated in 18% of eyes with 11% receiving treatment for DR and 14% receiving treatment for DME.

Data suggest the cumulative proportion of disease worsening through 4 years was 40% (95% confidence interval [CI], 36% - 45%) overall.

Then, the worsening rates were 45% (95% CI, 37% - 54%) in eyes with baseline mild NPDR, 40% (95% CI, 32% - 49%) with moderate NPDR, 26% (95% CI, 17% - 38%) with moderately severe NPDR, and 43% (95% CI, 34% - 53%) with severe or very severe NPDR on UWF-color masked images.

When stratified by baseline PPL status, 38% (95% CI, 31% - 45%) of eyes with color PPL and 43% (95% CI, 37% - 49%) without color PPL met the primary outcome of disease worsening (HR, 0.78; 95% CI, 0.57 - 1.08; P = .13).

Moreover, investigators noted the primary outcome rate was 50% (95% CI, 44% - 57%) in eyes with FA-PPL and 31% (95% CI, 25% - 38%) in eyes without FA PPL (HR, 1.72; 95% CI, 1.25 - 2.36; P <.001).

“These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes,” Glassman added.

The study, “Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time,” was published in JAMA Ophthalmology.

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