Diabetic Retinopathy Complications Predictable With Deep Capillary Plexus Nonperfusion

Ophthalmology office.
Ophthalmology office. Masked patient and doctor – Covid 19. Scan of the retina, an examination that allows you to precisely visualize the different parts of the eye. This imaging makes it possible to observe the retina in order to detect, for example, a retinal uplift with edema or a diabetic retinopathy. It is used to monitor wet AMD about every two months and complements the fundus to see if an injection of treatment is needed. OCT is also used to examine the optic nerve, and therefore screen for or monitor glaucoma. (Photo by: Pascal Bachelet/BSIP/Universal Images Group via Getty Images)
Lower vessel density and higher nonperfusion of deep capillary plexus on OCT-A is associated with diabetic retinopathy complications by 1 year.

Vessel density measures are typically used to assess retinal nonperfusion in the staging of diabetic retinopathy (DR). Recently, a novel metric, geometric perfusion deficit (GPD), has reliably been used to outline ischemic regions. Both metrics, when imaged with optical coherence tomography angiography (OCT-A) at middle and deep capillary plexus layers, can assist in predicting short-term complications in treatment-naïve patients with nonproliferative DR, according to a study published in Ophthalmology Retina.

Imaging in this prospective investigation took place at the Department of Ophthalmology at Northwestern University, Chicago, between June 2015 and July 2021. In 61 eyes of 49 individuals who were imaged at baseline, 1-year follow-up visits revealed that 18 eyes developed 1 or more outcomes such as center-involving diabetic macular edema (DME), new vitreous hemorrhage, high-risk proliferative DR (PDR), or treatment with laser or anti-vascular endothelial growth factor (anti-VEGF). Participants with lower vessel density and higher nonperfusion of middle and deep capillary plexus in GPD experienced a greater proportion of these events (P <.001).

In models adjusted for sex, baseline DR severity, and starting corrected visual acuity (VA), the associations were still significant (P =.046 to P <.001). Further, adjusted receiver operating characteristic (ROC) curves reflecting deep capillary plexus GPD imaging data reached sensitivity of 89% using a cutoff of higher than 12.8% for GPD, and specificity of up to 98% with a vessel density cutoff lower than 28.5%. Therefore, deep capillary plexus vessel density and GPD proved “robust indicators” irrespective of baseline disease level.

Patients with referable non-proliferative DR, particularly those who are treatment-naïve may not have as many follow-ups as those whose DR has progressed, the analysis noted — thus, predictors of greater risk can be helpful to personalize diagnostics and ensure faster treatment.

Prior research indicates the deep capillary plexus could reveal early vascular damage, including microaneurysms. Also, photoreceptor cells of animals have been linked to the release of reactive oxygen species, possibly adding to oxidative stress. Ischemia and oxidative stress promote VEGF upregulation. The deep capillary plexus is a close neighbor to photoreceptors, and it may be vulnerable to this process. Or, deep capillary nonperfusion alone prompts outer retinal ischemia.

“Since the DCP partially contributes to the metabolic needs of the photoreceptor layer, especially during dark adaptation, DCP ischemia from capillary closure in DR may compound photoreceptor metabolic stress, further upregulating VEGF and increasing DR complication risk in a vicious cycle,” the investigators explain.


Ong JX, Konopek N, Fukuyama H, Fawzi AA. Deep Capillary Nonperfusion on OCT Angiography Predicts Complications in Eyes with Referable Nonproliferative Diabetic Retinopathy. Ophthalmol Retina. Published online July, 5 2022. doi:10.1016/j.oret.2022.06.018