Discussion
Patients who are followed up and treated in the intensive care unit due to Covid-19 infection, in mechanical ventilation—including non-invasive ventilation—and at the prone position, are at risk for the development of ocular complications. The present study aimed to evaluate the eye care of patients recovering from Covid-19 infection to prevent vision loss as a result of ocular complications and to evaluate whether there is any ocular involvement during Covid-19 infection.
Although the main target of the SARS-CoV-2 virus is the respiratory tract, it is stated that it affects many other systems and that various symptoms are observed (9). Furthermore, coronavirus has been shown to cause serious eye diseases such as retinal vasculitis, anterior uveitis, optic neuritis in animals, ocular symptoms in humans are rare and mild (10).
The retina is considered as an extension of the central nervous system (CNS), therefore involvement may occur not only in the optic nerve (optic neuritis) but also in the retina (retinitis) in neuroinflammatory conditions and infections of the CNS (11). The CNS is protected from viruses by its multilayer barriers and the immune system, but viruses can affect the brain in various conditions such as direct brain damage, hypoxic damage, upregulated ACE-2 receptors, and immunodeficiency (12). It is well-known that ACE-2 receptors are widely distributed among many tissues and cell types, as well as in the conjunctiva. Some reports have shown that CoV-2 could potentially spread through direct or indirect contact with the mucous membranes of the eyes (13-15). Recent clinical and anatomopathological studies have defined endothelial damage as one of the most prominent causes of systemic vascular thromboembolic and inflammatory manifestations associated with Covid-19 (16-18). Therefore, vascular occlusion due to thrombotic sensitivity, chorioretinitis or vasculitis directly caused by the virus may occur in the retina. Considering that Sars-CoV-2 may exhibit direct ocular diffusion through two blood-retinal barriers (BRBs) or associated with thrombotic sensitivity identified in Covid-19, as reported in the brain, 8 of our patients who underwent retinal examination had intraretinal haemorrhages. Splintered haemorrhages in the temporal side of the optic disc were observed in 1 patient bilaterally and in 2 patients in the left eye. The Cotton wool spot was observed with a splinter haemorrhage in the temporal side of the optic disc in 1 patient. In 4 patients, intraretinal haemorrhages were observed in the macula in the arch. Marinho et al. detected microhemorrhages and cotton wool spots along the retinal arcade in 4 of 12 patients (19). But since cotton wool spots can be identified in a wide range of diseases (20,21) and the comorbidities of patients that could lead to this condition were not specified, it was stated that it is impossible to definitively determine whether these were pathological cotton wool spot conditions (22). In the present study, one patient with a cotton wool spot and retinal haemorrhage in the temporal side of the optic disc had diabetes mellitus, but there were no findings of diabetic retinopathy other than this haemorrhage. No statistically significant difference was observed between patients with haemorrhage in the retina and other patients in terms of both systemic diseases and laboratory parameters.
In three different studies conducted in China, Xia et al. could not find any relationship between the severity of Covid-19 infection and the frequency of conjunctivitis (23), whereas Guan et al (24) and Wu et al. (15) showed that the incidence of conjunctivitis and other ocular symptoms were higher in patients with severe pneumonia. In the present study, conjunctivitis was seen with a rate of 8.6%. The mechanism of how conjunctivitis occurs is still not fully understood. It may be endothelial dysfunction, vasculitis or the host response of conjunctival vessels due to Covid-19 infection (25).
More than 15% of patients affected by the Covid-19 pandemic are hospitalized and treated, a significant portion of which will require mechanical ventilation (26). Decrease in orbicular muscle tone due to neuromuscular blocking agents applied in patients under MV support and turning patients to the prone position, which is one of the treatment stages, increases the risk of exposure keratopathy in intensive care patients (27). Exposure keratopathy can be seen in patients who are connected to mechanical ventilation, especially in intensive care, and it can lead to progressive vision loss by causing microbial keratitis and ocular surface scarring (28)
A guideline has been approved by The Royal College of Ophthalmologists (RCOphth) in collaboration with the Intensive Care Association to prevent keratopathy in intensive care patients. It contains precautions that can be taken together with closing the eyelids (27). Kam et al. also suggested an eye care protocol in an eye care study in critically ill patients, emphasizing that clinicians should evaluate the closure of the eyelids in terms of lagophthalmos (29). To prevent the progression to keratopathy, eyelid closure and medical treatment was performed in patients in our intensive care unit with corneal epithelial defects seen in the first examinations during the examination phase. The intensive care staff caring for the patients was trained about the risk factors for developing keratopathy and the necessary preventive measures. Subsequently, the presence of corneal epithelial defect and keratopathy, which was observed in the first examinations with a rate of 7.5%, was not observed in the subsequent examinations. Six patients requiring treatment and care due to conditions such as corneal epithelial defect, conjunctivitis and keratitis could not be followed up because of complications related to Covid-19. It was observed that the corneal epithelial defect in one patient resolved in two days after eye care.
The incidence of chemosis in the conjunctiva in critically ill patients ranges from 9% to 80% (30). Chemosis is classified as mild, moderate or severe according to the degree of conjunctival prolapse. Vascular permeability and lymph duct dysfunction in the conjunctiva lead to chemosis (31). Mechanical ventilation increases jugular venous pressure and causes fluid to accumulate in ocular tissues. Long-term positive pressure ventilation and fluid electrolyte abnormalities in intensive care are factors that increase conjunctival chemosis (32). Chemosis may cause keratopathy and related complications by causing irregular tear distribution on the ocular surface according to its severity (33). Against the risk of developing keratopathy due to severe chemosis, especially in patients who are placed in the prone position, ocular evaluation should be performed before the patients are placed in the prone position, and eyelids should be taped by applying pomade to the eye (34). Our patients were hospitalized for a long time due to Covid-19 infection, and mild chemosis was observed at a rate of 20.4%, moderate chemosis at a rate of 10.8%, and severe chemosis at a rate of 4.3%, especially in patients who were intubated. It was observed that lagophthalmos developed due to oedema in the eyelids in one patient, and it was observed that severe chemosis and exposure keratopathy developed. Eyelid closure and lubrication treatment were initiated for the patient, and considering that closing the eyelids would not be sufficient, tarsoraphy was planned in the patient but treatment and follow-up could not be performed because the patient died due to complications related to Covid-19 infection the next day.
Schwartz et al. stated that subconjunctival bleeding may be more frequent in patients with Covid-19 infection treated in intensive care (35). In another study, subconjunctival haemorrhage was observed at a rate of 8.3% (36). In the present study, subconjunctival bleeding was observed in 3 (3.2%) patients. One of these cases was in the form of punctate bleeding foci with chemosis. It is thought that these bleedings may due to severe cough, vomiting due to intolerance of the drugs used, or due to the effect of anticoagulant drugs given in treatment to eliminate the risk of hypercoagulability of Covid-19 infection.
In the present study, it was aimed to prevent ocular complications that may occur in all critical patients in the intensive care unit by providing eye care information such as daily examination of the eyes, lubrication in the presence of lagophthalmos and closing the eyelids by taping. Eyecare in the intensive care unit and the application of treatments appropriate for ocular problems that may occur due to Covid-19 infection are vital for those who recover from Covid-19 infection to prevent vision loss and maintain quality of life.
The present study was conducted on patients who were being treated in intensive care. For this reason, as a limitation of our study, it was not possible to distinguish whether retinal haemorrhages were due to disease or drug use. We think that the application of systemic treatments to prevent the complications of Covid-19 infection before ophthalmological examination and hypoxia due to the disease makes it difficult to distinguish whether these findings are caused by Covid-19 infection or the treatment.
As a result, corneal abrasion due to lagophthalmos was observed in 10.3% of the patients who were followed up in the intensive care unit. Care should be taken in terms of exposure keratopathy, both due to not treating corneal abrasions, and also secondary to the development of severe chemosis and eyelid oedema in patients who are placed in the prone position. Daily eye examinations are required, especially in critical cases of Covid-19 under mechanical ventilation support.
We observed retinal haemorrhage at a rate of 8.6%. We observed that Covid-19 infection can directly cause endothelitis, thromboembolism or retinal haemorrhage and cotton wool spots due to the treatments used. There was no significant difference in terms of systemic disease and laboratory parameters in patients with haemorrhage in the retina compared to those without haemorrhage.