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.