Retinal Nonperfusion Characteristics on Ultra-Widefield Angiography in Eyes With Severe Nonproliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy

Abstract

IMPORTANCE Threshold of retinal nonperfusion for the development of proliferative diabetic retinopathy (PDR) is unclear.OBJECTIVES To identify a threshold of retinal nonperfusion for the presence of retinal neovascularization and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy (NPDR), PDR, neovascularization of the optic disc (NVD), and retinal neovascularization elsewhere (NVE). DESIGN, SETTING, AND PARTICIPANTS This cross-sectional image analysis study was performed between September 24, 2018, and October 24, 2018, at a multicenter national study in the United Kingdom. Baseline images were obtained from 2 completed randomized clinical trials (Ranibizumab for Diabetic Macular Edema Panretinal Photocoagulation [RDP] study and Clinical Efficacy of Intravitreal Aflibercept vs Panretinal Photocoagulation for Best Corrected Visual Acuity in Patients With Proliferative Diabetic Retinopathy at 52 Weeks [CLARITY] study). The RDP study recruited eyes with severe NPDR between April 1, 2014, and December 31, 2015, and the CLARITY study recruited eyes with PDR between August 22, 2014, and November 20, 2015. Ultra-widefield angiography images of eyes with no prior panretinal photocoagulation treatment were included. MAIN OUTCOMES AND MEASURES The total area of retinal nonperfusion, the area of posterior pole retinal nonperfusion, and the area of peripheral retinal nonperfusion were measured. RESULTS A total of 92 patients (92 eyes) were included in the study: 59 in the PDR group (mean [SD] age, 42 [15] years; 20 female [33.9%]) and 33 in the NPDR group (mean [SD] age, 63 [10] years; 3 female [9.1%]). Forty eyes had NVE and 19 had NVD with or without NVE.We identified a retinal nonperfusion threshold of 118.3 disc areas (DA) with a specificity of 84.9% (95% CI, 68.1% to 94.9%) for PDR. The median area of retinal nonperfusion was 67.8 DA (95% CI, 44.2 to 107.3 DA) in the NPDR eyes and 147.9 DA (95% CI, 127.4 to 173.5 DA) for eyes with proliferative changes, with a difference of 69.0 DA (95% CI, 42.2 to 97.7 DA; P < .001). No difference was found in the median area of posterior nonperfusion between NPDR and PDR, with a difference of 0 DA (95% CI, −6.7 to 5.2 DA; P = .56). As for peripheral nonperfusion, NPDR eyes measured 64.1 DA and PDR eyes measured 130.6 DA, with a difference of 70.8 DA (95% CI, 48.4 to 94.9 DA; P < .001). Eyes with NVD had the largest total area of retinal nonperfusion, with a difference of 65.1 DA (95% CI, 28.6 to 95.8 DA; P < .001) compared with eyes with only NVE.CONCLUSIONS AND RELEVANCE These findings suggest eyes with at least 107.3 DA of nonperfusion are at risk of proliferative disease, and eyes with NVD have the largest area of retinal nonperfusion.

Optical Coherence Tomography Angiography in Diabetes and Diabetic Retinopathy

“…Widefield fluorescein angiography revealed that peripheral retinal nonperfusion is a common finding in eyes with DR [86]. These peripheral nonperfusion lesions have been associated with higher risks of DR progression and support the hypothesis that peripheral nonperfusion may be a useful surrogate for and potential predictor of proliferative DR [87][88][89]. Therefore, numerous researchers have explored the use of widefield OCTA to identify peripheral capillary nonperfusion [90][91][92][93].…”

Relationships among Retinal Nonperfusion, Neovascularization, and Vascular Endothelial Growth Factor Levels in Quiescent Proliferative Diabetic Retinopathy

“…Baxter et al [13] demonstrated that a NP threshold size greater than 23% of the retinal image is associated with posterior segment NV. Nicholson et al [14] also suggested that at least 107.3 DA of NP are at risk of proliferative disease. This study adds the finding that the size of the NP area is also associated with the size of the NV area in PDR eyes.…”

“…UWF FA highlighted the importance of peripheral lesions in DR [11,12]. Quantitative analyses using UWF FA revealed that a larger NP area was associated with the presence of posterior NVs and NV at the disc area (NVD) [13][14][15].…”

Dynamic versus Static Ultra-widefield Fluorescein Angiography in Eyes with Diabetic Retinopathy: A Pilot Prospective Cross-sectional Study

“…In addition, images were analyzed and retinas graded by two independent examiners. It should be noted that greater peripheral DR lesions in UWFA have been associated with more severe DR [29][30][31] Limitations of this study were that we did not correct the peripheral warp present in UWFA. Since the most peripheral part of a UWFA image is magni ed, we evaluated retinal non-perfusion using NPI instead of evaluating absolute areas of non-perfusion.…”