To date, questions remain whether lesions in the retinal periphery influence the association between diabetic retinopathy (DR) severity and macular vessel density. Trying to shed light on this, a new study suggests DR severity in eyes with predominantly peripheral lesions (PPL) is primarily linked to peripheral, as opposed to posterior, non-perfusion.

The cross-sectional investigation, published in JAMA Ophthalmology, was conducted at a tertiary care center for diabetic eye disease and included 352 eyes of 225 patients with Type 1 or 2 diabetes who had undergone imaging between 2016 and 2019. The investigators imaged the superficial, intermediate and deep capillary plexus and choriocapillaris flow density with OCT angiography 3×3-mm macular scans, and determined DR severity and predominantly peripheral lesions with ultra-widefield color imaging.

Of the 352 eyes, 52% had mild non-proliferative diabetic retinopathy (NPDR), 20.2% had moderate NPDR and 27.8% had severe NPDR or proliferative diabetic retinopathy (PDR).

In eyes with no PPL (59.4%), the mean vessel density in the superficial capillary plexus was:

• Mild NPDR: 38.1%
• Moderate NPDR: 36.4%
• Severe NPDR or PDR: 34.1%
• The mean vessel density in the deep capillary plexus was:
• Mild NPDR: 45.8%
• Moderate NPDR: 45.8%
• Severe NPDR or PDR: 44.5%

Mean choriocapillaris flow density was:

• Mild NPDR: 69.7%  
• Moderate NPDR: 67.6%  
• Severe NPDR or PDR: 67.1%, decreased with increasing DR severity

These associations remained statistically significant even 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 (40.6%), mean vessel density in the superficial capillary plexus was the following:

• Mild NPDR: 34.1%
• Moderate NPDR: 35.2%
• Severe NPDR or PDR: 36.0%
• Deep capillary plexus:
• Mild NPDR: 44.5%
• Moderate NPDR: 45.4%
• Severe NPDR or PDR: 44.9%

Mean choriocapillaris flow density was:

• Mild NPDR: 67.1%
• Moderate NPDR: 69.3%
• Severe NPDR or PDR: 68.3%, which did not appear to change with increasing DR severity.

These findings suggest a potential need to stratify future OCT angiography studies of eyes with DR by the presence or absence of PPL, the researchers noted. If DR onset and worsening are associated with the location of retinal non-perfusion, assessment of global retinal non-perfusion using widefield angiography may improve the ability to evaluate DR severity and risk of DR worsening over time, the investigators added.