Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome

Abstract

Several optical coherence tomography angiography (OCT-A) studies have demonstrated retinal microvascular changes in patients post-SARS-CoV-2 infection, reflecting retinal-systemic microvasculature homology. Post-COVID-19 syndrome (PCS) entails persistent symptoms following SARS-CoV-2 infection. In this study, we investigated the retinal microvasculature in PCS patients using OCT-angiography and analysed the macular retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness via spectral domain-OCT (SD-OCT). Conducted at the Manchester Royal Eye Hospital, UK, this cross-sectional study compared 40 PCS participants with 40 healthy controls, who underwent ophthalmic assessments, SD-OCT, and OCT-A imaging. OCT-A images from the superficial capillary plexus (SCP) were analysed using an in-house specialised software, OCT-A vascular image analysis (OCTAVIA), measuring the mean large vessel and capillary intensity, vessel density, ischaemia areas, and foveal avascular zone (FAZ) area and circularity. RNFL and GCL thickness was measured using the OCT machine's software. Retinal evaluations occurred at an average of 15.2 ± 6.9 months post SARS-CoV-2 infection in PCS participants. Our findings revealed no significant differences between the PCS and control groups in the OCT-A parameters or RNFL and GCL thicknesses, indicating that no long-term damage ensued in the vascular bed or retinal layers within our cohort, providing a degree of reassurance for PCS patients.

Keywords: SD-OCT; ganglion cell layer; long COVID; nerve fibre layer; optical coherence tomography angiography (OCT-A); post-COVID-19 syndrome (PCS); retina.

Figure A1

A Bland-Altmann plot demonstrating the difference between the results measuring large vessel intensities using the OCTAVIA software on two occasions by the same assessor.

Figure A2

A scatterplot demonstrating the measurements of the area of the foveal avascular zone (FAZ) using Image J and the OCTAVIA software, outlining the relationship between a line of best fit compared to the 1:1 line.

Figure A3

A scatterplot demonstrating manual measurements of large vessel intensities in 10 × 10 OCT-A images compared with OCTAVIA software, outlining the relationship between the line of best fit and 1:1 line.

Figure 1

Spectral domain-optical coherence tomography (SD-OCT) of the macula obtained from Canon Xephilio OCT-A1 Machine (Canon Medical Systems Europe B.V©, Amstelveen, Netherlands) displaying a 10 × 10 mm macular image from a participant with post-COVID-19 syndrome segmented into nine EDTRS zones. The segments consist of superior outer, superior inner, nasal outer, nasal inner, inferior outer, inferior inner, temporal outer, temporal inner, and foveal (central) zones. (a) Displays the average thickness of the macular retinal nerve fibre layer (mRNFL) in nine EDTRS zones. (b) Displays the average thickness of the macular ganglion cell layer (mGCL) in nine EDTRS zones.

Figure 2

Analysis of the macular 10 × 10 mm and 4 × 4 mm optical coherence tomography-angiography (OCT-A) images performed by our inhouse software. (a) 10 × 10 mm macular OCT-Angiography image of the right eye. (b) Binarisation of the 10 × 10 mm macular OCT-A image as a processing step. (c) Final segmentation of the image following removal of optic disc and the central 4 × 4 mm area which was analysed in separate dedicated 4 × 4 mm images (d) 4 × 4 mm macular OCT-Angiography image of the right eye. (e) Binarisation of the 4 × 4 mm macular OCT-A image. (f) Final segmentation of the 4 × 4 mm image with parafoveal and perifoveal zones highlighted.