key: cord-0800559-prjlzlsd authors: Lecler, Augustin; Cotton, François; Lersy, François; Kremer, Stéphane; Héran, Françoise title: Ocular MRI Findings in Patients with Severe COVID-19: A Retrospective Multicenter Observational Study date: 2021-02-16 journal: Radiology DOI: 10.1148/radiol.2021204394 sha: f00e53828a84806c1f6482cc605528009ad55602 doc_id: 800559 cord_uid: prjlzlsd COVID-19 may affect various organs. This paper reports 9 patients (1/9 [11%] woman and 8/9 [89%] men, mean age 56 ± 13 years) with globe MRI abnormalities obtained from a multicenter cohort of 129 patients presenting with severe COVID-19 from March 4th to May 1st, 2020. 9/129 (7%) patients had one or several FLAIR-WI hyperintense nodules of the posterior pole of the globe. All patients had nodules in the macular region, 8/9 (89%) had bilateral nodules, 2/9 (22%) had nodules outside the macular region. Screening of these patients might improve the management of potentially severe ophthalmological manifestations of the virus. See also the editorial by Kirsch. COVID-19 has been reported to be associated with ophthalmological abnormalities, such as conjunctivitis, chemosis, retinopathy or optic neuritis (3) (4) (5) (6) (7) . MRI orbital abnormalities have been reported but no MRI studies have been published about globe abnormalities to the best of our knowledge (8) (9) (10) . This paper reports a series of patients with severe COVID-19 presenting with abnormal MRI findings of the globe. This retrospective observational multicenter study was initiated by the French Society of Neuroradiology (SFNR). It included clinical and imaging data of consecutive patients presenting with severe COVID-19 who underwent brain MRI from 16 hospitals including 11 university hospitals and 5 general hospitals from March 4 th to May 1 st 2020. The study was approved by the ethical committee of Strasbourg University Hospital (CE-2020-37) Clinical and ophthalmological data were extracted from the patients' electronic medical records. Virological assessment was made with quantitative real-time RT-PCR tests for SARS-CoV-2 nucleic acid performed on nasopharyngeal or lower respiratory tract swabs and cerebrospinal fluid. Imaging studies were conducted either on 1.5-or 3-Tesla MRI. MRI examinations were anonymized and analyzed by two neuroradiologists with 9 years ("blinded") and 30 years ("blinded") of experience in ophthalmological imaging. A total of 129 patients (43/129 [33%] women and 86/129 [67%] men, mean age 63 ± 14 years) was included for analysis from March 4 th to May 1 st 2020 ( Figure 1 ). Among them, 9/129 (7%) patients (1/9 [11%] woman and 8/9 [89%] men, mean age 56 ± 13 years) had abnormal MRI findings of the globe consisting in the presence of one or several nodules of the posterior pole of the globe. 2/9 (22%) patients had diabetes, 6/9 (67%) were obese, 2/9 (22%) had hypertension and none of them had asthma. 6/9 (67%) patients underwent brain MRI due to delayed awakening despite discontinuation of sedation, 2/9 (22%) due to persisting agitation and confusion after awakening and 1/9 (11%) for agitation and hallucinations. The nodules of the posterior pole of the globe were all hyperintense on FLAIR-WI, isointense on T1-WI and showed no enhancement after gadolinium injection. No abnormal susceptibility was seen on susceptibility-weighted images. All 9/9 (100%) patients had nodules in the macular region, 8/9 (89%) had bilateral nodules, 2/9 (22%) had nodules outside the macular region (figure 2). Two studies displayed findings from the OCT, which is a more sensitive tool than fundoscopy (14, 15) . They reported hyper-reflective lesions at the level of ganglion cell and inner plexiform layers on OCT, as well as the presence of cotton wool exudates which are markers of vascular disease severity. Interestingly, these abnormalities were more prominent at the papillomacular bundle in both eyes, which was also the preferential location for the nodules visible on MRI in our study. Only one of our patients with a macular nodule underwent OCT, showing no abnormal findings. Although the nature of these nodules remains unknown, several hypotheses might be considered since human and animal coronaviruses were reported to cause inflammation of varying ocular segments, causing retinitis, choroiditis, retinal detachment or optic neuritis in the literature (17, 18) . A wide variety of mechanisms have been described, such as direct infiltration of the retina and retina pigment epithelium by the virus, vasculitis, or autoimmune process, the latter mechanism being more frequent to explain retinal damages (17) . The onset of an ocular microangiopathic syndrome is highly prevalent after viral infections. SARS-Cov-2 is known to target the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor, which is largely expressed in the retina and the choroid. ACE2 is the primary enzyme of the vasoprotective axis of the renin-angiotensin system in the retina (19) . Its downregulation might induce the development of retinal ischemia (15) . Another possible hypothesis is a Valsalva retinopathy secondary to orbital proptosis which can occur when the ocular venous system is affected by the increased central venous pressure, leading to an inadequate ocular venous drainage. This situation can occur in patients hospitalized in intensive care units, especially those in the prone position or intubated, which was the case for almost all our patients with severe COVID-19 (20, 21) . In clinical practice, our study suggests that a dedicated exploration of the globes with high resolution 3D T2-WI and post-contrast fat-suppressed T1-WI MRI, as well as fundoscopy and OCT, should be considered in all patients presenting with severe COVID-19 to detect posterior pole nodules. Severe eye problems might largely go unnoticed as these patients are often treated in intensive care units for much more severe, life-threatening conditions. Our data support the need for a screening and follow-up of these patients to provide appropriate treatment and improve the management of potentially severe ophthalmological manifestations. Our study suffers from several limitations. Firstly, it is a retrospective study with a limited number of patients and no control group. Secondly, we analyzed ocular abnormalities on brain MRI performed in patients with severe COVID infections. Dedicated ocular MRI sequences, especially high-resolution MRI sequences, were not available, preventing a precise description and understanding of ocular abnormalities. Thirdly, ophthalmological data were missing for the majority of our patients, because no systematic ophthalmological examination was performed in our patients with severe COVID-19 hospitalized in intensive care unit, thus clinical-radiological correlations were limited. Fourthly, no ocular or conjunctival sampling for detection of SARS-CoV-2 was available, thus it is impossible to assess the direct causality of the virus in our findings. We do not know whether a high viral load was linked to more severe ophthalmological findings. Fifthly, pathologic material was lacking. Finally, we lacked follow-up data to assess whether the MRI abnormalities were transient or not and their consequences on visual acuity. 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