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New highlights on this subject from a pandemic hospital in Turkey

Ocular surface infection is uncommon in COVID-19 patients, but may occur in the initial stages or later in the course of the disease.  A study, carried out between 1 May and 30 June 2020 on a fairly large population of COVID-19 patients, confirmed what other reports have found, and highlighted questions that still remain open.  Site of the study was the Diyarbakir Gazi Yasargil Education and Research Hospital in  Diyarbakir, Turkey, which was declared a pandemic hospital by the Republic of Turkey Ministry of Health. Three hundred fifty-nine COVID-19 patients with age ranging between 20 and 91 years were evaluated.  The majority, 294 subjects (81.9%), were treated in the inpatient clinic and 65 (18.1%) were treated in the ICU with respiratory support by mechanical ventilation.  Ocular signs and symptoms were observed in 16 subjects (4.5%), while one patient had conjunctival hyperemia as the first and only manifestation of COVID-19.  Ocular symptoms including conjunctival hyperemia, chemosis, epiphora, increased secretion and photophobia, were defined as conjunctivitis and were found in 4 subjects (1.1%) treated in the inpatient clinic and 3 (0.84%) patients treated in the hospital. Subconjunctival hemorrhage developed in five patients (1.4%), 3 in the ICU, and 2 in the inpatient clinic. Vitreous hemorrhage developed in one patient with diabetes who had not been attending his routine visits for 4 months due to the COVID-19 outbreak. Ocular symptoms appeared 3 days after COVID-19 respiratory symptoms. Conjunctival chemosis was not observed in any patient in the inpatient clinic, but developed in 2 patients (0.56%) in the ICU. One of them was on mechanical ventilation. 

“Ophthalmologic findings may be the first sign or may occur during the treatment process of the patients with COVİD-19. These findings seem to be related to the severity of the disease,” said Hasan Öncül, first author of the study.  “While the rate of ocular disease was 12 out of 294 (4.1%) in patients treated in the inpatient clinic, it increased to 4 out of 65 (6.2%) in intensive care patients.”  

Mechanisms of eye infection are still unclear

The mechanisms through which Sars-CoV-2 infects the eye are still unclear, the authors noted.  Direct transmission by exposure of the conjunctiva to infective respiratory droplets has been hypothesized, but conjunctival swabs are rarely positive for SARS-COV-2.  On the other hand, “negative results may be related to low viral concentration and poor diagnostic methods,” they pointed out. 

Other potential mechanisms responsible for conjunctivitis may be vasculitis or endothelial dysfunction.  Finally, conjunctivitis may be related with the inflammatory processes underlying COVID-19. C-reactive protein (CRP) values were found to be higher in patients with conjunctivitis symptoms in this and other studies.  However, the authors noted that “studies with more patients are needed to evaluate the relationship between ocular disorders and inflammation-related laboratory parameter in COVID-19 patients.”

Other findings that involve alterations of the ocular vascular structure, such as conjunctival chemosis and subconjunctival hemorrhage, may be a consequence of treatment rather than a manifestation of COVID-19.  Mechanical ventilation for respiratory stress works by applying a positive pressure, which may cause changes in the ocular vascular structure.  Also anticoagulant drugs, severe cough or vomiting due to intolerance of medications may have been the cause of some subconjunctival hemorrhage.  

The cause of vitreous hemorrhage, which developed in a patient with proliferative diabetic retinopathy, is also uncertain.  Metabolic dysfunction, COVID- vasculopathy, or endothelial dysfunction triggered by COVID-19 disease may have caused this condition. But, it is not possible to know whether a vitreous hemorrhage is a condition that occurs in the normal course of proliferative diabetic retinopathy or is a condition triggered by COVID-19 disease,” the authors wrote.

How COVID-19 affects the retina is an area that remains to be investigated, since high risk of transmission and isolation requirements have limited the possibility to examine the back of the eye in these patients. 

“It is known that patients with COVID 19 have some disorders in the vascular system and many deaths due to thromboembolic complications have been described. It cannot be expected that this disease affecting the vascular system will not affect an organ with a dense vascular network such as the eye, and particularly the retinal vascular system. However, invasive and non-invasive tests cannot be performed in these patients due to the high risk of contamination. Unfortunately, this situation limits our correct interpretation. In the future, OCT and OCT angiography may reveal the effects of COVID-19 on the retina,” Dr. Öncül said.

Öncül H, Öncül FY, Alakus MF, Çağlayan M, Dag U. Ocular findings in patients with coronavirus disease 2019 (COVID-19) in an outbreak hospital. J Med Virol. 2020 Aug 10:10.1002/jmv.26412. doi: 10.1002/jmv.26412. PMID: 32776614