Diabetic Retinopathy Severity Associated With Central Retinal Vessel Density in Eyes Without PPL

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Central retinal vessel density is associated with diabetic retinopathy severity in eyes without, but not with, predominantly peripheral lesions (PPL) according to a study published in JAMA Ophthalmology.

Central retinal vessel density is associated with diabetic retinopathy (DR) severity in eyes without, but not with, predominantly peripheral lesions (PPL) according to a study published in JAMA Ophthalmology. Consequently, the findings suggest “a potential need to stratify future optical coherence tomography angiography (OCTA) studies of eyes with DR by the presence or absence of PPL,” authors wrote.

Early Treatment of Diabetic Retinopathy Study (ETDRS) DR severity grading has been the standard criterion for assessing the disease for decades, as the classification system is reproducible and increasing grades are closely associated with the risk of worsening DR.

However, recent advances in retinal imaging have enabled more detailed visualizations of the retinal structure and function. One approach, which uses ultra-widefield (UWF) imaging is able to identify PPL in the retinal periphery.

“The prevalence of eyes with PPL in patients with DR ranges between 37% and 41%,” researchers wrote. “Compared with eyes without PPL (ie, a more central distribution of DR lesions), eyes with PPL are at higher risk of developing advanced retinopathy, with a 3.2-fold increased risk of a DR progression of 2 steps or more and a 4.7-fold increased risk for progression to proliferative DR (PDR) at 4 years.”


Because PPL is associated with DR progression and due to the association of OCTA with DR severity, investigators set out to compare OCTA metrics across various DR severity levels in eyes with or without PPL.

All patients included in the cross-sectional observational study (N = 225; 352 eyes) were adults with either type 1 diabetes (T1D) or type 2 diabetes (T2D). Each participant also underwent OCTA, spectral-domain optical coherence tomography, and 200° Optos UWF color fundus photographic imaging between February 2016 and December 2019. Furthermore, “only eyes with mild nonproliferative DR (NPDR) or worse were included in the study.”

The majority of participants were male (55.6%) with a mean (SD) age of 52.1 (15.1) years, while 143 eyes had PPL and 209 eyes did not. The analysis revealed:

  • Patients with PPL were more likely to have T1D (76 of 90 [84.4%] vs 77 of 135 [57.0%]) and a longer mean (SD) duration of diabetes (35.7 [15.1] vs 25.5 [13.7] years) than those without PPL
  • 183 eyes (52.0%) had mild NPDR, 71 eyes (20.2%) had moderate NPDR, and 98 eyes (27.8%) had severe NPDR or proliferative diabetic retinopathy (PDR)
  • In eyes with no PPL the mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 38.1% [4.7%]; moderate NPDR, 36.4% [4.6%]; severe NPDR or PDR, 34.1% [4.1%]; P < .001) and the deep capillary plexus (mild NPDR, 45.8% [3.0%]; moderate NPDR, 45.8% [2.2%]; severe NPDR or PDR, 44.5% [1.9%]; P = .002) decreased with increasing DR severity
  • In eyes with no PPL the mean (SD) choriocapillaris flow density (mild NPDR, 69.7% [6.2%]; moderate NPDR, 67.6% [5.6%]; severe NPDR or PDR, 67.1% [5.6%]; P = .01), also decreased with increasing DR severity
  • Associations remained statistically significant after correcting for age, signal strength index, spherical equivalent, duration of diabetes, type of diabetes, and correlation between eyes of the same patient

In eyes with PPL the following factors did not appear to change with increasing DR severity:

  • Mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 34.1% [4.1%]; Moderate NPDR, 35.2% [4.1%]; severe NPDR or PDR, 36.0% [4.3%]; P = .42)
  • The deep capillary plexus (mild NPDR, 44.5% [1.7%]; moderate NPDR, 45.4% [1.4%]; severe NPDR or PDR, 44.9% [1.5%]; P = .81)
  • Mean (SD) choriocapillaris flow density (mild NPDR, 67.1% [5.6%]; moderate NPDR, 69.3% [4.6%]; severe NPDR or PDR, 68.3% [5.6%]; P = .49)

Eyes included in the study were limited due to exclusion of those with diabetic macular edema and prior treatment with anti-vascular endothelial growth factor, corticosteroids, or panretinal photocoagulation. The relatively small number of eyes included and the large percentage of eyes from individuals with T1D mark limitations to the study, as results may not fully represent associations in eyes of patients with T2D.

Future studies may include those with diabetic macular edema and individuals receiving treatment and could evaluate eyes with each type of diabetes separately.

“Because PPL are present in approximately 40% of all eyes with DR, these findings may have important implications for future studies evaluating OCTA metrics in people with DR,” researchers concluded. “If DR onset and worsening are associated with the location of retinal nonperfusion, global retinal nonperfusion assessment using widefield angiography may improve the ability of OCTA to assess DR severity and risk of DR worsening over time.”


Ashraf M, Sampani K, Rageh A, Silva PS, Aiello LP, Sun JK. Interaction between the distribution of diabetic retinopathy lesions and the association of optical coherence tomography angiography scans with diabetic retinopathy severity. JAMA Ophthlamol. Published online October 29, 2020. doi:10.1001/jamaophthalmol.2020.4516