COVID-19 is a systemic disease that affects the whole body, especially the respiratory tract. The main symptoms of COVID-19 are fever, cough, sore throat, and loss of smell and taste. Ocular symptoms can also be seen and sometimes even present as initial findings . Bertoli et al. reported conjunctivitis, Kawasaki disease, Guillain-Barré syndrome, polyneuritis, encephalopathy, dry eye, exposure keratopathy, chemosis, infectious keratitis, ischemic optic neuropathy, and Horner syndrome in patients with COVID-19 . Wu et al. found ocular symptoms, including conjunctivitis, conjunctival hyperemia, epiphora, chemosis and increased secretion in 12 (31.6%) of 38 patients with COVID-19 . In another study, Zhou et al. noted the presence of conjunctival symptoms, such as chemosis, conjunctival hyperemia, itching, foreign body sensation, and watering in eight (6.6%) of 121 COVID-19 cases . Hon et al., evaluating 56 patients with COVID-19, observed ocular symptoms in 15 (27%) patients and summarized these symptoms as itching, redness, foreign body sensation, dry eyes, watering and floating objects. The authors also noted that six (11%) patients had developed ocular symptoms prior to respiratory system symptoms .
Marinho et al. examined 12 patients with COVID-19 and found soft exudate in the retina, retinal hemorrhage, and hyperreflectivity in ganglion cells and inner plexiform on optical coherence tomography . In another study, Virgo et al. observed acute macular neuroretinopathy in a patient with COVID-19 and paracentral moderate acute retinopathy in another case . Tostmann et al. described eye pain in 31 (34.4%) of 90 patients with COVID-19  while Mao et al. reported visual loss in three (1.4%) of 214 patients . In COVID-19 cases, Guillain-Barré syndrome manifesting with diplopia, third or sixth nerve involvement, and nystagmus, as well as its eye component, Miller Fisher syndrome, have also been described [16, 17]. However, although literature studies have shown that coronaviruses cause anterior uveitis, retinitis, vasculitis and choroiditis in animals, these findings have not been found in humans .
The etiopathogenesis of ocular findings seen in COVID-19 has been investigated in various studies but has not yet been fully elucidated. Considering the pathogenesis of conjunctivitis symptoms, it is thought that the virus uses the ocular surface as an entry point through the mediation of angiotensin-converting enzyme 2 receptors . Peripheral nerve damage, demyelination and inflammation in diplopia are held responsible for visual impairment . In Guillain-Barré and Miller Fisher syndromes, the autoimmune mechanism has been suggested to be effective against Schwann cells and myelin antigens [16, 17, 20].
Savastano et al. compared the OCTA findings of 80 patients with COVID-19 to 30 healthy controls. The authors reported the mean RNFL value as 94.09 ± 10.77 µm for the COVID-19 group and 96.50 ± 7.78 µm for the control group. Although this difference was not statistically significant, the RNFL value of the COVID-19 control was found to be lower than the control group (p = 0.26) . In the current study, the mean RNFL was 119.33 ± 3.88 µm before COVID-19 and 117.50 ± 3.92 µm after the disease. The decrease in the RNFL value after the disease was statistically significant (p < 0.001). We consider that the reason for this is inflammation and retinal nerve fiber damage, as also described in previous studies .
Various OCTA studies have been conducted in relation to COVID-19 and its vascular etiopathogenesis. Abrishami et al. compared the OCTA findings of 30 patients with COVID-19 (nine requiring hospitalized treatment) obtained at two weeks after recovery to 23 healthy individuals. The total, parafoveal and foveal vascular density values of SCP and DCP were found to be statistically significantly lower in the COVID-19 group (p = 0.001, p = 0.002, p = 0.004, p = 0.001, p = 0.011, and p = 0.003, respectively . Similarly, Cennoma et al. evaluated the OCTA values at six months after recovery in 40 patients who had developed pneumonia due to COVID-19 and compared them to 40 healthy individuals. The authors reported that the total vascular densities of the optic disc and SCP and the total, parafoveal and foveal vascular densities of DCP were statistically significantly lower in the COVID-19 group compared to the control group (p < 0.001, p = 0.038, p = 0.029, p = 0.016, and p = 0.027, respectively). 7 In another study, Savastano et al. found the radial peripapillary plexus perfusion density to be statistically significantly lower in individuals with COVID-19 compared to the control group, and this difference statistically significant (p = 0.041) .
In a study evaluating OCTA findings in 27 patients with a history of COVID-19 at one week after recovery from the disease compared to a healthy control group, Turker et al. observed a statistically significant decrease in the parafoveal vascular density values of SCP and DCP in the COVID-19 group (p < 0.05). However, the foveal vascular density did not statistically significant differ between the two groups. In the same study, the CBF value was reported to be 2.15 ± 0.23 mm2 for the COVID-19 group and 2.08 ± 0.11 mm2 for the control group, indicating a statistically significant difference (p = 0.042) . In our study, when we compared the retinal and optic disc vascular density values of the same patients before and after COVID-19, we found no statistically significant results. While the mean CBF value of the patients was 2.00 ± 0.13 mm2 before COVID-19, it was 2.08 ± 0.23 mm2 after the disease. When the pre- and post-disease CBF values, there was a statistically significant increase in the post-disease CBF value (p = 0.003).
In an autopsy performed on a person who died due to COVID-19, SARS-CoV-2 ribonucleic acid was detected in the retina . Since there are ACE2 receptors in the retina and choroid, these tissues also have binding sites for the SARS-CoV-2 virus . Studies have shown that COVID-19 causes vascular endothelial damage and vascular complications. Although endothelial damage, tissue edema, inflammatory cell migration, intravascular coagulation cascade, and endotheliitis are considered to be involved in vascular pathogenesis, the exact mechanism of this cascade remains unknown [24–26]. Inflammation and increased vascular permeability caused by COVID-19 are held responsible for the increase in CBF [22, 27]. We consider that despite the increase in the CBF value, the vascular density values of the retina and optic disc were not altered by the disease due to the autoregulation mechanism in the retina . In addition, the retina contains a blood retinal barrier, but there is no such barrier in the choroid. Therefore, while inflammation and increased vascular permeability cause an increase in CBF, no change is observed in retinal vascular density values. It has been suggested that individuals that have had severe COVID-19 can develop hypoxia, ischemia, and microvascular damage in the retina [6, 22, 28]. The absence of significant changes before and after COVID-19 in our study despite the decrease in retinal vascular density values in the literature may be related to the patients in previous studies suffering from a more severe form the disease requiring hospitalization.
Savastano et al. found the mean SCT value as 310.463 ± 81.60 µm in the patients with COVID-19 and 293.5 ± 86.56 µm in the control group. Although not statistically significant, the mean SCT value was higher in individuals who had a history of COVID-19 (p = 0.34) . In our study, the mean SCT value was measured as 247.33 ± 7.65 µm before the disease and 273.08 ± 4.92 µm after the disease, and this increase was found to be statistically significant (p = 0.001).
Tan et al. listed the causes of an altered choroidal thickness as age-related changes, gender differences, sympathetic system activity, metabolic diseases (diabetes mellitus, hypercholesterolemia, etc.), changes due to choroidal hyperperfusion (hypertension), systemic inflammatory conditions (ankylosing spondylitis, Raynaud’s phenomenon, Vogt-Koyanagi-Harada disease, Behçet’s disease, and sarcoidosis), cerebral vasculature changes (Alzheimer’s disease), microarteriolar occlusions (sickle cell disease), choroidal tumors and choroidal metastases . We also consider that the increase in the choroidal thickness of our patients was caused by inflammation, increased vascular permeability, and increased CBF.
Considering the limitations of this study, it can be stated that the major limitation was the small number of patients. Another limitation is that none of the patients in this study required intensive care during active infection, and none had a severe form of the disease. Although the patients in our study did not experience severe COVID-19, we found changes in their CBF, SCT and RNFL values compared to the pre-disease period. The retina, choroid and optic disc may be affected more in severe COVID-19, and this may be reflected in results in the presence of larger data. We consider that our study will contribute to the literature by guiding further research to be conducted with larger samples.