Coronavirus has been shown to manifest in other parts of the human body including the gastrointestinal system and the eye besides the respiratory system [13, 14]. Most of the clinical studies about coronavirus have focused on the respiratory system because of its life-threatening nature. Evaluation of other organ systems should be considered and this may provide valuable information so as to uncover the unknown mechanisms of tissue injury.
Ocular involvement in COVID-19 patients is limited to the conjunctiva and tear film layer, as reported in previous studies [5, 6, 15]. It has been shown that viral ribonucleic acid can be detected in the retina of infected people . In a study by Seah et al., coronaviruses were shown to be capable of producing various ocular manifestations from anterior segment pathologies like conjunctivitis and anterior uveitis to vision-threatening conditions like retinitis and optic neuritis .
The factors that trigger severe disease in individuals infected with COVID-19 are not completely understood. It has been shown that hyper-inflammation and coagulopathy contribute to disease severity and death in patients with COVID-19 . In addition, clinical studies suggest that severe COVID-19 infection reflects a confluence of vascular dysfunction and disruption in thrombosis mechanisms .
The choroid is the vascular part of the eye and has an important role in the pathogenesis of several ocular diseases. The choroidal circulation is a dense network of capillaries located behind the RPE cell layer. The choriocapillaris which forms the innermost layer of the choroid is the fundamental blood supply to the outer retina. Because of the high metabolic demand of the photoreceptor layer, the choroid receives the plurality (65–85%) of the blood that is supplied to the retinal structures . Impaired choroidal blood flow is associated with several ocular diseases, such as glaucoma, retinitis pigmentosa, degenerative myopia and age-related macular degeneration. Histological analysis has shown that changes in the choroidal interstitial stroma may occur in eyes with age-related macular degeneration due to edema, fibrosis, and inflammation with cellular infiltration .
In current study, we provide for the first time evidence of choriocapillaris ischemia in eyes of patients with COVID-19 infection. We compared the luminal and stromal area of the choroid in patients with COVID-19 and healthy subjects by the binarization technique with Image-J. Our findings showed that the mean total choroidal, the mean luminal, and the mean stromal areas were statistically decreased in eyes of patients with COVID-19 when compared to healthy subjects.
Choroidal thickness is a parameter that varies substantially both in healthy and in pathological conditions. It decreases from the macula to the periphery and is at its maximum subfoveally. Choroidal thickness is not a true representative of the entire choroidal vasculature as an objective marker. Measuring CVI enables us to have information about both vascular and stromal components of the choroid . Xin et al. Reported that CVI was shown to be independent of systemic and ocular factors like age, axial length, intraocular pressure, or systolic blood pressure . However, choroidal thickness may vary depending on these factors. In a study by Xin et al., the mean value of CVI was reported as 70.12% for healthy subjects . In our study, this ratio was 76.11% in controls. Agarwal et al. Found the subfoveal CVI as 65.61% in their study by including 345 eyes of healthy subjects with an average age of 61 years . In our study, we found CVI as 76.11%, but the average age of our control group was 37 years. Some studies purposed to determine normative values for CVI in healthy people and these studies investigated whether there is an age-related change in CVI value [21, 22]. Jaeryung et al. Showed no significant correlations of CVI with age . In contrast, Ruiz-Medrano et al. reported that CVI to be significantly higher in the group with subjects under 18 years of age compared with the group of older people .
Some reports have been published regarding CVI and its implementations in the evaluation, diagnosis, and treatment of retinochoroidal diseases such as central serous chorioretinopathy, polypoidal choroidal vasculopathy, panuveitis, and diabetic retinopathy [24–28]. Agrawal et al. assessed CVI in people with posterior uveitis and panuveitis and they showed an increased CVI, which decreased after follow-up period . Some choroidal changes such as decreased CVI were also reported in eyes with serpiginous choroiditis . Shulin et al. demonstrated a lower CVI during the active period of Vogt-Koyanagi-Harada Disease and decreased CVI during the active phase were because of choroidal stromal edema and infiltration by inflammatory cells .
In our study, we observed that the average CVI value decreased in patients with COVID-19 infection compared to healthy subjects. According to our hypothesis, it is possible that vascular damage, hypercoagulability, and hyper-inflammation factors, which have been shown to be involved in the pathogenesis of COVID-19 infection, might have led to ischemia of choriocapillaris and decreased the CVI. In addition, the reduction in the luminal area, stromal area, and CVI revealed by Image-J might be explained by the secondary result of the lack of oxygen demand.
We also compared choroidal thickness changes between the patients with COVID-19 and the control group. The subfoveal, 1500 µm nasal, and 1500 µm temporal choroid thickness were thinner in patients with COVID-19 than in healthy subjects. Although the choroidal thickness was decreased at all points, as CVI in patient group, we could not detect a statistically significant difference.
Limitations of our study include a relatively small sample size and absence of detailed ocular examinations owing to the logistical challenges of managing the COVID-19 patients. Binarization of choroidal images was performed only in the right eye of each participant, therefore inter-eye differences might have an effect on the results.