COVID-19 Clinical Care: Brazilian Study Finds Retinal Lesions In Patients With Severe COVID-19

COVID-19 Clinical Care: A new study by researchers from the Federal University of Sao Paulo-Brazil and Faculdade de Medicina do ABC-Brazil have discovered that the inner retina of certain severe COVID-19 patients may harbor acute vascular lesions in the form of flame-shaped hemorrhages and "cotton wool" spots. However the researchers are not clear as to what could be causing these retinal lesions.


 
The study findings were published in the British Journal of Ophthalmology. https://bjo.bmj.com/content/early/2020/10/15/bjophthalmol-2020-317576
 
Dr Leonardo Amarante Pereira, an Ophthalmologist from the Faculdade de Medicina do ABC, in Santo Andre told Thailand Medical News,  "Our study results suggest that the retina might be affected in patients with COVID-19. However, given the clinical characteristics of the disease, confounding factors are difficult to control. Further studies with larger samples are necessary to assess this possibility.”
 
According to Dr Amarante Pereira, one confounding factor could be the common use of vasoactive drugs in critically ill patients. He explained that patients under vasoactive support can experience blood pressure fluctuations, and acute blood pressure peaks can lead to retinal hemorrhages and cotton wool spots.
 
Simply by analyzing a patient's retina, Dr Amarante Pereira continued, the physician can have a good idea of what is happening in the rest of the patient's body.
 
He said,"Since we do not completely understand the pathogenicity of SARS-CoV-2, the dilated-eye examination can give us some clues.”
 
If acute inner retinal vasculature lesions are found in these patients, Dr Amarante Pereira said, "We have to consider that the rest of patient's organs are also suffering from microvascular dysfunction and ischemia. And that needs to be considered when treating and giving support to these patients."
 
The research was performed in May with inpatients at a Sao Paulo-area hospital that is a referral center for treatment of patients with COVID-19.
 
The study involved 18 patients, half were male and the median age was 62. Seventeen were admitted to the intensive-care unit (ICU) at some point during their hospital stay, 13 needed invasive mechanical ventilation and seven needed vasoactive pharmacological support.
 
It was reported that twelve patients had a previous diagnosis of high blood pressure, and nine had diabetes mellitus. No patients were known to have ocular symptoms.
 
Upon admission, a retina specialist performed dilated-eye examinations in all 18 patients. These exams showed abnormalities in 10 of the 18 patients, the most common findings being flame-shaped hemorrhages in four patients (22.2%) and cotton wool spots in three (16.7%), with one patient having both types of lesion.
 
It was reported in the study that retinal sectorial pallor suggestive of acute retinal ischemia was found in one patient. Other findings included peripheral retinal hemorrhages in two patients, retinal pigment epithelium hyperplasia in one, choroidal nevus in one, and macular hemorrhages and hard exudates in one.
 
As a result of the study team observing chronic alterations like retinal pigment epithelium hypertrophy and choroidal nevus, they point out that the presence of abnormalities on dilated-eye examination in 10 of the 18 patients was "not necessarily related to SARS-CoV-2 infection."
 
The study team added, however, that the acute lesions to the inner retinal vasculature and retinal sectorial pallor in some cases appeared in the absence of vasoactive pharmacological support, diabetes, or high blood pressure, "suggesting that they might be related to COVID-19 itself."
 
The retina could be affected either by direct tissue damage by SARS-CoV-2 and its immunogenicity or by the thrombotic complications that have been reported to have a remarkably high incidence in patients with COVID-19 admitted to the ICU. https://www.sciencedirect.com/science/article/abs/pii/S0889159120303573
https://www.sciencedirect.com/science/article/abs/pii/S0049384820301201
 
Direct infection and immune injury are thought to be involved in nerve damage in COVID-19. The inner retina is a neuronal tissue, and may also be injured by SARS-CoV-2 as has been reported for the central nervous system. SARS-CoV-2 RNA has already been identified in retinas of deceased patients with COVID-19 and other viruses are known to cause similar retinal injuries. These include HIV, dengue virus and Zika virus. https://www.mdpi.com/1999-4915/10/10/530
 
https://www.sciencedirect.com/science/article/abs/pii/S1350946211000279
 
It has been reported that critically ill patients with COVID-19 in the ICU have thrombotic complications at rates as high as 31%. https://www.sciencedirect.com/science/article/abs/pii/S0049384820301201
 
Although more information is needed, the coagulopathy appears to be related to the profound inflammatory response against the SARS-CoV-2 and not to intrinsic viral activity. This is because the retina is one of the most metabolically active tissues in the body and its terminal circulation is particularly sensible to ischaemic events. We found cotton wool spots, which are thought to result from occlusion of terminal retinal arterioles in the nerve fibres and ganglion cell layer, with consequent retina ischaemia and infarction, and retinal sectorial pallor, possibly caused by branch arterial occlusion secondary to thromboembolic phenomena.
 
A spokesperson for the American Academy of Ophthalmology, Dr Raj Maturi, told media that because vascular occlusive disease is a known risk of COVID-19, "The eye, with a very visible vascular surface (the retina) is thus an excellent place to review such manifestations."
 
He added, that the research "reinforces the systemic nature of COVID in some patients. Many physicians are using anti-coagulation in COVID-affected individuals, and seeing significant ocular occlusive changes confirms the usefulness of continuing anti-coagulation treatment." (Dr Maturi was not involved in the study.)
 
The study team concluded, “Our results suggest that the retina might be affected in patients with COVID-19. However, given the clinical characteristics of the disease, confounding factors are difficult to control. Further studies with larger samples are necessary to assess this possibility. Nevertheless, we are sharing these preliminary results in an effort to inform the scientific community about the possibility of retina lesions in patients with severe COVID-19.”
 
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