Lesions Predominantly Peripheral to ETDRS Fields on Ultrawide Field Images (UWFI) Predict Markedly Increased Risk of Diabetic Retinopathy (DR) Progression

Abstract

Purpose: To determine if distribution of DR lesions outside standard ETDRS fields identified on UWFI predict DR progression.

Methods: Mydriatic 7-field ETDRS photos and UWFI were obtained in 200 eyes (100 subjects) at baseline. Two masked graders independently evaluated the images, with adjudication by a third. UWFI were assessed as having either predominantly peripheral lesions (PPL) outside ETDRS coverage or not having predominance of lesions peripheral to the ETDRS area. Followup ETDRS imaging was obtained 4.13 ± 0.29 years after baseline.

Results: Baseline DR by ETDRS photos: none 12.5% eyes; mild nonproliferative DR (NPDR) 22.5%; moderate 30%; severe/very severe 8.1% and proliferative DR (PDR) 27%. Of 91% participants alive at followup, 71 (140 eyes) were re-imaged (78% subjects, 77% eyes). There were no significant differences in age, DM duration, 2-year prior HbA1c or DR severity between eyes that did or did not complete followup. In eyes with no ETDRS DR at baseline (N=25), DR lesions peripheral to ETDRS fields were observed in 8 (32%). Of the 17 (68%) eyes re-imaged, 83% of eyes with baseline peripheral only DR developed ETDRS photo evident DR compared to only 27% of eyes with no DR evident anywhere (p=0.05). In eyes with NPDR (N=112) at baseline, 88 (79%) were re-imaged at followup, PPL were present in 44 (52%) and DR progression occurred in 34 (40%). Baseline DR severity was not different between eyes with or w/o PPL (p=0.86). Compared to eyes w/o PPL, eyes with PPL had 86% increased risk of ≥1 step clinical DR progression (28% vs 52%,p=0.03), 4-fold increased risk of ≥2 step DR progression (8% vs 32%p=0.007) and a 3-fold increased risk of developing PDR (10% vs 32%,p=0.002), all still significant after adjusting for baseline DR severity and DM duration.

Conclusions: Nearly 1/3 of patients with no DR evident on ETDRS photos may have DR evident in the periphery with 3-fold more progression to DR on ETDRS photos over 4 years. In patients with baseline NPDR, DR lesions predominantly peripheral to the area imaged by ETDRS photos are associated with markedly increased risk of DR progression over 4 years, independent of baseline DR severity. If these findings are confirmed, peripheral retinal evaluation may become essential in both clinical and research settings to more accurately determine risk of DR progression in eyes with no DR or NPDR.

Keywords: 499 diabetic retinopathy • 461 clinical (human) or epidemiologic studies: natural history • 550 imaging/image analysis: clinical