LAUSR

DESIGN OF STUDY. Prospective multicenter longitudinal observational study PURPOSE. To determine whether predominantly peripheral lesions (PPL) identified on UWF imaging and angiographic risk factors are associated with increased disease worsening beyond the risk associated with baseline ETDRS DR severity score (DRSS). METHODS. A total 544 study eyes with nonproliferative DR (NPDR) from 367 adult participants with diabetes. 200° UWF-colour images were collected at each annual visit through 4 years. UWF-fluorescein angiography (FA) images imaging was performed at baseline, 1 and 4 years. A centralized reading center graded DR severity and PPL on UWF-colour (colour-PPL) and UWF-FA (FA-PPL). PPL were defined as DR lesions with a greater extent outside versus inside the standard ETDRS fields. Initiation of treatment for DR and/or DME was at investigator discretion. The primary outcome was disease worsening over 4 years, defined as 2 or more steps DRSS worsening within ETDRS fields on UWF-colour images or receipt of DR treatment. RESULTS. The 4-year disease worsening rates were 45% for eyes with mild NPDR at baseline, 40% for moderate NPDR, 26% for moderately-severe NPDR, and 43% for severe NPDR. At baseline, 41% of eyes had colour-PPL and 46% had FA-PPL. Disease worsening was not associated with baseline colour-PPL (present vs absent: 38% vs 43%; HR, 0.78; 95% CI, 0.57–1.08; p= 0.13) but was associated with baseline FA-PPL (present vs absent: 50% vs 31%; HR, 1.72; 95% CI, 1.25–2.36; p< 0.001). CONCLUSIONS. Although no relationship was identified with colour-PPL, presence of FA-PPL was associated with greater risk of disease worsening over 4 years, independent of baseline DR severity level. These results suggest that evaluation of the retinal far periphery is important in understanding which eyes with NPDR are at higher risk for future disease worsening. Peripheral findings on UWF-FA should be considered for incorporation in future DR staging systems.