Swept-source OCTA quantification of capillary closure predicts ETDRS severity staging of NPDR

Abstract

PurposeTo test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to the gold standard ETDRS grading scheme.Methods105 patients with diabetes, either without retinopathy or with different degrees of retinopathy (NPDR up to ETDRS grade 53), were prospectively evaluated using swept-source OCTA (SS-OCTA, PlexElite, Carl Zeiss Meditec) with 15×9 mm and 3×3 mm angiography protocols. Seven-field photographs of the fundus were obtained for ETDRS staging. Eyes from age-matched healthy subjects were also imaged as control.ResultsIn eyes of patients with type 2 diabetes without retinopathy or ETDRS levels 20 and 35, retinal capillary closure was in the macular area, with predominant alterations in the parafoveal retinal circulation (inner ring). Retinal capillary closure in ETDRS stages 43–53 becomes predominant in the retinal midperiphery with vessel density average values of 25.2±7.9 (p=0.001) in ETDRS 43 and 23.5±3.4 (p=0.001) in ETDRS 47–53, when evaluating extended areas of 15×9 protocol. Combination of acquisition protocols 3×3 mm and 15×9 mm, using SS-OCTA, allows discrimination between eyes with mild NPDR (ETDRS 10, 20, 35) and eyes with moderate-to-severe NPDR (ETDRS grades 43–53).ConclusionsRetinal capillary closure, quantified by SS-OCTA, can identify NPDR severity progression. It is located mainly in the perifoveal retinal capillary circulation in the initial stages of NPDR, whereas the retinal midperiphery is predominantly affected in moderate-to-severe NPDR.

A Central Role for Ischemia and OCTA Metrics to Follow DR Progression

“…Recent clinical studies using optical coherence tomography–angiography (OCTA) show that vessel closure occurs very early in diabetic retinal disease and is initiated in the macula [ 4 ]. Later on, as the disease progresses with remodeling of the retinal circulation and an altered retinal blood flow distribution probably through preferential arteriovenous preferential channels vessel closure develops and even appear to predominate in more peripheral regions of the retina [ 5 ].…”

“…Ashton, who has contributed so extensively to our knowledge of DR, remarked in 1974 that ‘we must continue to look for more fundamental scientific investigations and at the same time develop new ways of examining the diabetic retina in an effort to unravel the still unsolved mysteries of diabetic retinopathy [ 15 ]. Metrics of retinal vessel density obtained with OCTA in a noninvasive manner, allowing repeated examinations, appear to identify the eyes/patients at a higher risk for increase in severity, thus promoting a larger role for precision medicine in the management of DR in individual patients [ 4 , 5 , 6 , 11 ].…”

“…The study shows that retinal vessel closure is an early finding in the macular area of the diabetic retina and that this alteration increases as the retinopathy progresses in severity involving later more peripheral regions of the retina. Furthermore, SS-OCTA metrics of retinal vessel closure, allowing measurements to be performed in the macula and in more peripheral regions of the retina, may offer an objective and easier to perform alternative to ETDRS severity grading [ 5 ].…”

“…Regional distribution of the DR lesions in the retina may reflect risk factors and may be important in defining the stage of diabetic retinopathy [ 3 , 5 , 16 ]. Vessel closure in the midperiphery in a diabetic retina is indicative of an advanced stage of retinopathy, whereas vessel closure limited to the perifovea suggests a milder stage of the disease [ 5 ].…”

Microaneurysm Turnover in Mild Non-Proliferative Diabetic Retinopathy is Associated with Progression and Development of Vision-Threatening Complications: A 5-Year Longitudinal Study

“…In fact, recently published work by our group [ 8 ] was able to demonstrate, using optical coherence tomography angiography (OCTA), that eyes that showed progression of their disease had a consistent decrease in the median values of macular vessel density (VD). Now that we can use OCTA to evaluate the retinal capillary network, this technique has also shown promising results in disease staging and identification of risk factors for progression [ 21 ], such as foveal avascular zone (FAZ) changes [ 22 ] and macular vs. periphery capillary closure [ 23 , 24 ]. However, OCTA is still not available in every ophthalmic clinic or primary health care unit.…”