Neovascularization Elsewhere Morphology Linked With Ischemic Change Severity

Ophtalmological practice, Geneva, Switzerland, Carrying out OCT angiography to detect the presence of neovascularisation, angiography with autofluorescence and optical coherence tomography. (Photo by: BSIP/Universal Images Group via Getty Images)
The study examined the phenomenon in patients with proliferative diabetic retinopathy.

Neovascularization elsewhere (NVE) size increases were significantly associated with severity of ischemic changes, suggesting that the presence of NVE is associated with severe ischemia in patients with proliferative diabetic retinopathy (PDR), according to research results published in Ophthalmology Retina.1 

Through a retrospective observational imaging study, researchers both evaluated and quantified enlarged NVE in eyes with PDR via widefield swept-source optical coherence tomography angiography (SS OCT-A) imaging. 

Participants underwent ultra-widefield fundus photography and imaging, widefield SS OCT-A scans, slit lamp examination, detailed fundoscopy, and HbA1c testing. OCT-A images were reviewed by 2 researchers and measured for area and vascular density of each NVE; nonperfusion areas were measured via ultra-widefield fundus scans. 

The primary study outcome was vascular density of NVEs detected on either 5 12×12 mm2 or 2 15×9 mm2 SS OCT-A panoramic vitreoretinal interface slab images. NVEs are typically defined as those more than 1 disc diameter outside the margin of the disc.2

The final analysis included 46 NVEs from 25 eyes of 21 patients (16 men; mean age, 51±13.6 years). Mean duration of follow-up (the period between the 2 OCT-A examinations) was 4.84±3.04 months. 

At baseline, NVE in OCT-A was 1.85±2.91 mm2, and mean vascular density of NVE was 73.9±14.6%. At the final visit, these values were 2.14±3.14 mm2 and 65.3±17.1%, respectively.

Of the 25 eyes, 3 were treatment naïve; subsequent panretinal photocoagulation was initiated in 12% and additional PC was performed in 44% of eyes. No additional treatment was needed in 44% of eyes. 

Researchers evaluated the correlation between age, HbA1c, ischemic index, and NVE size and density changes per month. At baseline, ischemic index was significantly associated with average NVE size change. A comparison of baseline and final areas of 46 NVEs showed that 34 became more than 1.05 times larger compared with baseline; 7 were between 0.95 and 0.105 times larger, and 5 were less than 0.95 times smaller relative to baseline. 

In an analysis of the 34 expanding NVEs that grew more than 1.05 times larger, NVEs could be classified into round-shaped (68.1%) or ramified (38.2%) patterns. In the round-shaped pattern, the spread was centered around the vein, while in the ramified pattern it extended straight from the tip of the NVE. NVE area at baseline and final visit did not differ between shape groups, and neither size change (mm2/month) nor density (%/month) were different. 

However, the density of the NVE at baseline and final OCT-A was significantly higher in the round-shaped group compared with the ramified group. No differences were noted in terms of HbA1c level, age, or PC number, but there was a significant difference in baseline ischemic index. 

Study limitations include those inherent to retrospective research and the small sample size, as well as the technical impossibility of distinguishing between neovascularization outside 300 µm of the inner limiting membrane, the limited utility associated with the performance of manual segmentation and measurements, and a lack of repeatability tests in this study. 

“By adopting [vitreoretinal interface] slab methods, we detected the size and density changes of NVEs,” the research explains. “Furthermore, we classified NVEs based on round and ramified growth patterns. Further studies are needed to examine the relationship between the morphology and the severity of PDR. This study highlighted the importance of comprehensively evaluating the morphology, area, and [vascular density] of NVEs.” 


1. Shiraki A, Sakimoto S, Eguchi M, et al. Analysis of progressive neovascularization in diabetic retinopathy using widefield optical coherence tomography angiography. Ophthalmol Retina. Published online May 26, 2021. doi: 10.1016/j.oret.2021.05.001

2. Ishibazawa A, Nagaoka T, Yokota H, et al. Characteristics of retinal neovascularization in proliferative diabetic retinopathy imaged by optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57(14):6247-6255.