Commentary: Role of optical coherence tomography-angiography in diabetes mellitus: Utility in diabetic retinopathy and a comparison with fluorescein angiography in vision threatening diabetic retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of blindness in the middle-aged population, and among them, diabetic macular edema (DME) is the leading cause of moderate visual loss caused by the breakdown of inner and outer blood-retinal barriers.[1] Aside from fundus fluorescein angiography (FFA), current technology like OCT angiography (OCTA) and spectral-domain OCT has had a substantial impact on our understanding of the pathophysiology of DR and DME.[2]

OCTA is a relatively new noninvasive imaging modality that can examine each of the three retinal capillary plexuses, i.e., superficial, middle, and deep capillary plexus (DCP), and also the choriocapillaris. FFA, on the other hand, is an invasive imaging method that only focuses on the superficial capillary plexus (SCP). OCTA has added new paradigms to our understanding of various ophthalmic diseases.[3] In DR, information provided by OCTA supplements the information obtained using FFA, including the presence of collaterals, neovascularization elsewhere (NVE) or of the optic disc, capillary nonperfusion areas, and abnormalities of the FAZ,[4] and can detect them even before they are appreciated clinically or on fundus photography.[5] Structural OCT B scan with a flow overlay will help in differentiating between intraretinal microvascular abnormalities (IRMA) and NVE. IRMA will have flow signals within the retina under the internal limiting membrane (ILM), whereas NVEs appear as flow voids above the ILM and will be seen in preretinal space thus aids in decision making.[1] Moreover, follow-up of rare cases with persistent NV despite full pan-retinal photocoagulation for possible neovascular growth is easy to perform with OCTA.[6] Widefield OCTA has emerged as a promising tool with the potential to replicate or replace FFA in diagnosing or monitoring the progression of the disease. Couturier et al.[7] showed that the detection rate of capillary nonperfusion areas was higher with widefield OCTA than ultrawide field FFA. This is attributed to the fact that OCTA, unlike FFA, is not affected by leakage and can delineate the abnormal vasculature and capillary nonperfusion areas. These studies suggest that widefield OCTA has the potential to replace ultrawide field FFA in the future, in diagnosing and monitoring the changes in DR.

Various imaging biomarkers on OCTA are vessel density index in SCP and DCP, measurement of the foveal avascular zone (FAZ) in SCP and DCP, and fractal dimension (FD). However, only a few of them have the potential to serve in guiding treatment for DME and also monitoring progression. FAZ metrics could be more easily measured by OCTA than FFA. FAZ in SCP and DCP increases in size with the severity of DR. Lee et al.[8] showed that a mean area of the FAZ was higher in the DCP than in the SCP and poor responder DME eyes exhibited a larger FAZ area in the DCP. There is no change in FAZ in the SCP, whereas FAZ in the DCP decreases post three initial monthly intravitreal anti-VEGF injections in eyes with DME.[7] The fractal analysis evaluates the microvascular alterations and also the geometric alterations of the retinal vasculature. Compared to normal subjects, FD in the SCP and DCP has shown a considerable decrease in DME. Ting et al.[9] documented structural changes using FD within the retinal microvasculature related to the severity of DR and vascular and metabolic risk factors in patients.

When comparing OCTA to FFA, there are a number of factors that limit its therapeutic utility. The cost of OCTA is higher than that of FFA, which limits its use. Even with widefield OCTA of 12 mm × 12 mm scans, the limited view with OCTA is a limitation. Though some of it may be offset with more readily available OCTA collages, it is controversial whether the OCTA has good sensitivity for detecting MAs compared to FFA, which is the earliest sign of DR. The limited reliability of OCTA and the poor visibility of the DCP in people with macular edema have been cited as concerns. As a result, FAZ measurement, particularly in DCP with numerous cystic areas on OCT, may not be a reliable indicator of the treatment responsiveness to anti-VEGF agents. While analyzing the images, issues like projection and motion artifacts are typically encountered.

The study by Shaikh et al.[10] adds to our understanding of the utility of OCTA in DR in the setting of the Indian subcontinent. OCTA can currently detect diabetic alterations in early-stage DR, discriminate early neovascularization, and detect diabetic macular ischemia. The next major task will be to standardize these measurements and generate population-specific normative data sets.