Abstract
The main objective of this study was to evaluate the retinas of severely or critically ill COVID-19 patients during their hospital stay, at varying time points after symptoms onset. This was a case series observed during May 2020 in two referral centers for COVID-19 treatment in Rio de Janeiro, Brazil. 47 eyes from 25 hospitalized patients with severe or critical confirmed illness were evaluated. A handheld retinal camera was used to acquire bilateral fundus images at several time points after symptoms onset. Electronic health records were retrospectively analyzed and clinical data collected. Severe and critical diseases were noticed in 52% (13/25) and 48% (12/25) of enrolled patients, respectively. Retinal changes were present in 12% (3/25) of patients: a 35 year-old male demonstrated bilateral nerve fiber layer infarcts and microhemorrhages in the papillomacular bundle, but required mechanical ventilation and developed severe anemia and systemic hypotension, acute kidney injury and neurologic symptoms during the course of the disease (critical illness); a 56 year-old male, who required full enoxaparin anticoagulation due to particularly elevated D-dimer (>5.0 mcg/mL), demonstrated unilateral and isolated flame-shaped hemorrhages; and a 49 year-old hypertensive male showed bilateral and discrete retinal dot and blot microhemorrhages. The other 22 patients evaluated did not demonstrate convincing retinal changes upon examination. There was no correlation between disease severity and admission serum levels of CRP, D-dimer and ferritin. This was the first study to show that vascular retinal changes may be present in not insignificant numbers of severe or critical COVID-19 inpatients. These retinal changes, only seen after morbid developments, were likely secondary to clinical intercurrences or comorbidities instead of a direct damage by SARS-CoV-2, and may be important and easily accessible outcome measures of therapeutic interventions and sentinels of neurologic and systemic diseases during COVID-19 pandemic.
Highlights
The novel coronavirus disease in 2019 (COVID-19) has been responsible for over 16 million confirmed cases worldwide, with more than 800,000 confirmed deaths [1]
The respiratory symptoms that characterize COVID-19 [2, 3] may be associated with a wide range of neurological complications, including cerebrovascular diseases, usually related to severe or critical disease phenotypes, and which may significantly contribute to patients morbidity and mortality [4]
Evidence of an intraocular renin-angiotensin system regulating important aspects of ocular physiology has been demonstrated [12, 14], and viral ribonucleic acid has been detected by reverse transcription polymerase chain reaction (RT-PCR) in retinal biopsies of deceased COVID-19 patients [15], which together endorses the rationale for an ophthalmological syndrome of COVID-19, with some pathophysiology still unknown
Summary
The novel coronavirus disease in 2019 (COVID-19) has been responsible for over 16 million confirmed cases worldwide, with more than 800,000 confirmed deaths [1]. The pathophysiology behind COVID-19 associated brain damage is still poorly understood [5], and both a direct viral neurotropism or indirect mechanisms involving dysregulated inflammatory cytokines release (“cytokine storm”), vascular endothelial injury and hypercoagulation cascades triggering/ disseminated intravascular coagulation are under investigation [4, 6]. Evidence of an intraocular renin-angiotensin system regulating important aspects of ocular physiology (e.g. retinal vascular tone and aqueous dynamic) has been demonstrated [12, 14], and viral ribonucleic acid has been detected by reverse transcription polymerase chain reaction (RT-PCR) in retinal biopsies of deceased COVID-19 patients [15], which together endorses the rationale for an ophthalmological syndrome of COVID-19, with some pathophysiology still unknown
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