Detecting papillary neovascularization in proliferative diabetic retinopathy using optical coherence tomography angiography

Abstract

Diabetic retinopathy (DR) affects almost 30% of patients with diabetes mellitus (DM), and proliferative diabetic retinopathy (PDR) involves 9% of them with consequent severe visual impairment (Cheung et al. 2010). Proliferative diabetic retinopathy (PDR) represents a heightened risk of life-threatening systemic vascular complications and occurs due to glycaemic impairment and long periods of metabolic alterations. The natural evolution of PDR is characterized by a series of clinical signs, starting with retinal ischaemia and an abnormal activation of vascular endothelial growth factor (VEGF). This alteration leads to retinal neovascularization and the appearance of retinal haemorrhage, fibrosis and vitreous bleeding in the later stages of the disease. Although the neovascularization in PDR is detectable just by ophthalmoscopy, the advantage of fluorescein angiography (FA) is that it can identify capillary non-perfusion and leakage area. Recently, a new method of retinal vessel analysis without dye injection has been introduced. Optical coherence tomography angiography (OCT-A) is based on a split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. This algorithm allows the detection and visualization of blood flow and morphology of retinal vessels, ischaemia with special emphasis on the retinal and papillary microvasculature. (Savastano et al. 2015; Minnella et al. 2016). Nevertheless, OCT-A cannot ascertain whether neovascularizations are leaking, and this technique is therefore also accompanied with information loss. The aim of this study was to evaluate whether OCT-A provides better visualization of neovascularization of the optic disc (NVD) in patients with PDR than conventional FA. A total of 10 eyes from six patients (mean age of 56 ± 4.2 years; female-to-male ratio 2:4), with both a clinical and FA diagnosis of PDR and evidence of NVD, were included in the study. The testing was performed using FA (Spectralis, Heidelberg Engineering, Heidelberg, Germany) and OCT-A using the AngioVue system with the commercially available XR-Avanti spectral domain-OCT (SD-OCT) device (OptoVue, Freemont, California). Study participants were included in the study if they were affected by diabetes mellitus (type I in two patients and type II in four patients) and had evidence of PDR, as detected by FA. All the patients underwent OCT-A examination using both protocols 3 × 3 and 6 × 6 mm OCT-A volumes at 2.6 seconds per each. We evaluated NVD by comparing the FA and OCT-A images. Optical coherence tomography angiography (OCT-A) produced multiple scans; therefore, the best OCT-A image to detect the new vessel architecture was selected for use in the study. All of the images were assessed by two observers, blinded to the image origins (M.C.S. and M.F.), who outlined the greatest linear dimension (GLD) and area (pixel2) of NVD. The outline was manually delineated using Photoshop (CS5), and the inter-observer agreement analyses were high (0.92 Cohen coefficient; K = 0.2, p < 0.01). In addition, the number of NVD images on the disc area was assessed. Using FA, severe and moderate PDR was observed in six and four eyes, respectively. In all study eyes, the OCT-A images allowed for the detailed visualization of the papillary neovascularizations. The clinical characteristics and neovascular area details are also shown in Table 1. These features could not be assessed by FA. Both study examiners described the features of disc neovascularization with the presence or absence of a ‘sea fan’ aspect (yes/no, Y/N) and the ability to recognize the neovascularization using OCT-A (yes/no, Y/N). We found that all of the disc proliferation had the ‘sea fan’ aspect (100%) and OCT-A was able to define the disc proliferation in all eyes examined (100%). In contrast, the neovascular papillary proliferation features could not be visualized by FA due to intense early and late leakage (Fig. 1-3). The results of the current study suggest that OCT-A may be a useful method to analyse disc neovascularization in PDR. This new tool allows for the analysis of blood flow into the vessels without the need for dye injections. Optical coherence tomography angiography (OCT-A) shows the blood flow in the neovascularizations without artefacts due to dye leakage. The capability of OCT-A to detect the blood flow into the choroidal neovascularization similarly with vascular retinal pigment epithelium detachment in age-related macular degeneration has been recently described (Lumbroso et al. 2015, Clemens et al. 2016; Wang et al. 2016). Structural OCT does not allow for the visualization of vessels, only tissue analyses. By contrast, functional OCT using SSADA technology is able to detect the blood flow in the vessels. In our study, we used this technique to determine the level of NVD in diabetic patients who showed FA papillary diabetic proliferation. Using OCT-A, we were able to determine the number, course, size and extension of NVD, features that could not be properly assessed using FA. During the FA examination, the papillary neovascularizations are only detectable for a few seconds immediately following the dye injection. The subsequent dye diffusion does not allow for the visualization of the vessel profile, only indirect signs of neovascularizations. Using OCT-A, we were able to observe direct morphological signs of pathologic microvessels. The ability to define NVD without dye injection has been previously described (Ishibazawa et al. 2015). Ishibazawa and colleagues reported the potential of this new tool for the detection of NVD, avoiding the leakage effect. In conclusion, OCT B-scan analysis and FA are both useful for the diagnosis of PDR. The introduction of OCT-A into the clinical practice is useful to monitor different NVD subtypes, their development, the efficacy of treatment regimes and to define new vessel morphological details. Moreover, in future, we hope that an automatic quantitative method to assess the diseased area will become available.