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Original Investigation
April 30, 2020

Quantification of Retinal Nonperfusion and Neovascularization With Ultrawidefield Fluorescein Angiography in Patients With Diabetes and Associated Characteristics of Advanced Disease

Author Affiliations
  • 1W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor
  • 2Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
  • 3Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 4Keck School of Medicine, Department of Ophthalmology, University of Southern California, Los Angeles
JAMA Ophthalmol. Published online April 30, 2020. doi:10.1001/jamaophthalmol.2020.1257
Key Points

Question  Which biomarkers calculated from ultrawidefield fluorescein images of patients with diabetes are most associated with demographic risk factors and retinopathy progression?

Findings  In this case series, male sex, black race/ethnicity, and presence of vitreous hemorrhage were most strongly associated with greater areas of nonperfusion and neovascularization, and a retinal nonperfusion threshold of 77.48 mm2 may be associated with increased risk for progression. Given the study’s design, statistical significance could not be established.

Meaning  These results suggest which factors may indicate higher risk of severe disease progression, and eyes with at least 77.48 mm2 nonperfusion are at risk of proliferative retinopathy.


Importance  Quantification of nonperfusion (NP) and neovascularization (NV) in diabetic retinopathy (DR) may identify better biomarkers of disease progression.

Objective  To identify demographic risk factors and markers of advanced DR that are associated with increased areas of NP and NV in eyes with disease ranging from no DR but diagnosed as having diabetes to proliferative DR (PDR) and to calculate a threshold total area of NP that may be associated with an increased risk of PDR.

Design, Setting, and Participants  This retrospective case series was performed on ultrawidefield fluorescein angiography (UWF FA) images from January 2009 to May 2018 at the University of Michigan Kellogg Eye Center. A total of 363 participants (651 eyes) diagnosed as having type 1 or 2 diabetes receiving UWF FA were included. Exclusion criteria included previous panretinal photocoagulation (PRP) and poor-quality images (eg, vitreous hemorrhage and significant cataract).

Main Outcomes and Measures  The surface areas in millimeters squared of the foveal avascular zone; total NP; NP at posterior pole, midperiphery, and far periphery; total NV; NV at posterior pole, midperiphery, and far periphery were measured.

Results  Of 363 patients, most were male (205 patients [56.5%]) and white (247 [68%]) or black (77 [21.2%]). The mean (SD) age was 59.4 (13.7) years. Seventy-six eyes with no DR, 92 with mild NPDR, 144 with moderate NPDR, 101 with severe NPDR, 220 with PDR, and 18 with DR of unknown severity were included. Male sex had a positive association with total NP (difference, 15.72; 95% CI, 4.83-26.61; P = .005); black race/ethnicity with total NV (difference, 2.32; 95% CI, 0.09-4.55; P = .04); and vitreous hemorrhage with total NP (difference, 30.00; 95% CI, 5.26-54.75; P = .02). A threshold total NP area of 77.48 mm2 (95% CI, 54.24-92.66 mm2) was identified, at greater than which patients may have an increased risk of developing PDR (sensitivity of 59.5% and specificity of 73.6%).

Conclusions and Relevance  Our results indicate NP and NV can be quantified on UWF FA. These biomarkers interpreted with demographic risk factors may help predict disease progression. Conclusions are limited by ascertainment and information biases because the results are from retrospective data.

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