The present study investigated the retinal findings, macular thickness, subfoveal and peripapillary CVI, RNFL, and BMO-MRW using OCT in patients recovered from COVID-19. Retinal hemorrhage and CWS were observed as the retinal findings in the CG. In the choroidal region, the mean subfoveal and peripapillary CVI were significantly higher than in the HG. Although the difference was not statistically significant, the mean RNFL thickness was 3 µm, and the mean BMO-MRW was 17 µm thicker compared with the HG.
Ocular findings, which are thought to be associated with the COVID-19, are reported in recent publications. (17–22). The detection of the virus in the retinal biopsies of who died from COVID-19 proved the presence of the virus in retinal layers (23). The retinal hemorrhages, dilated veins, tortuous vessels and CWS due to retinal microangiopathy caused by COVID-19 were the most cited signs in the studies (18, 19). The CWS in the retinal region is most commonly associated with diabetes mellitus, AIDS, and systemic hypertension. It occurs secondary to ischemia-induced by retinal arteriole obstruction (24). Factors that interrupt the focal axoplasmic flow in the retinal nerve fiber layer lead to the accumulation of intra-axonal organelles (25). SARS-CoV-2 has been shown to cause endotheliitis and vasculitis due to direct viral infection of endothelial cells in arterial and venous circulations (26, 27). Endotheliitis causes microvascular dysfunction and tissue ischemia. In the present study, we evaluated asymptomatic individuals who had not previously known systemic diseases and recovered from COVID-19 and, interestingly, found two patients with CWS and one with retinal hemorrhage after the recovery period. Although it is hard to conclude that these findings directly resulted from COVID-19, all systemic investigations were regular in these patients, so we thought these conditions might be associated with SARS-CoV-2.
The dense vascular choroid layer is one of the structures influenced by many physiologic variables and disorders such as systemic inflammation, infections, and vascular disorganization (28). Choroidal changes in viral infection/inflammation might play an essential role in several posterior segment diseases because the choroid supplies blood flow to the retinal pigmented epithelium, photoreceptors, and the prelaminar portion of the optic nerve (29–31). Agrawal et al. suggested that CVI might be a better and relatively more stable and objective quantitative marker to analyze choroid than choroidal thickness alone (21). Other coronaviruses have been shown only to cause choroiditis in animal models (16). In the current study, subfoveal and peripapillary CVI were significantly higher in the CG than the HG. Both LA and SA may have been affected by the combination of hemodynamic instability and systemic immunologic process created by direct viral infection/inflammation. It is not clear whether the affection in the choroidal area is due to an inflammatory response to the virus or the known endothelial damage characteristic of the virus. Invernizzi et al. found significant enlargement in the mean retinal arteries and vein diameters in patients COVID-19 who had symptoms within 30 days. They reported these changes might have had similar mechanisms with the reported pulmonary vascular enlargement (18, 32). This dilation was explained by the increased blood flow due to the inflammatory response (18, 32). Savastano et al. reported that subfoveal choroid was thicker (310.463 ± 81.60 µm) in post-COVID-19 disease compared with healthy controls (293.5 ± 86.56 µm) (33). We also found that subfoveal and peripapillary choroidal vascular areas were also had enlargement compared with the controls.
There is evidence indicating that coronaviruses cause optic neuritis in animal models, and SARS-CoV-2 has a potential neurotropic effect (11, 16, 34, 35). Burgos-Blasco et al. reported a mean 4.3 µm increase in RNFL thickness compared with previous data in patients with COVID-19 (35). We found similar results in patients recovered from COVID-19. The mean RNFL and BMO-MRW were thicker than in the HG, but these changes were not statistically significant. SARS-CoV-2 might affect the optic nerve by inflammation, or its direct neurotrophic effect may lead to increased RNFL thickness and BMO-MRW.
The limited number of study subjects and the absence of OCT results obtained before or at the acute phase of the disease are the limitations of this study. The lack of long-term consequences, the correlation between CVI changes and indocyanine green angiography and optical coherence tomography angiography is also a weakness of our study. Studies with larger populations and more prolonged duration may contribute to better evaluations of the effects of SARS-CoV-2 on the retina, choroid, and optic nerve.
In conclusion, the study's patient group consisted of young, healthy healthcare workers without any known systemic disease, all of whom were affected by COVID-19, a mean of 2.05 ± 0.5 months ago. We suggest that this study's retinal and choroidal results should be considered to be related to SARS-CoV-2. To the best of our knowledge, this study showed for the first time that SARS-CoV-2 might lead to an increase in subfoveal and peripapillary CVI values after recovery. Prospective studies with larger populations will contribute to our understanding of the impact of COVID-19 on the eye.