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  • Comprehensive Ophthalmology, Retina/Vitreous

    Case 1

    Review of: Impending Central Retinal Vein Occlusion in a Patient with Coronavirus Disease 2019 (COVID-19)

    Invernizzi A, Pellegrini M, Messenio D, et al. Ocular Immunology and Inflammation, November 2020 

    Case 2

    Review of: Case Report: Central Retinal Artery Occlusion in a COVID-19 Patient

    Montesel A, Bucolo C, Mouvet V, et al. Frontiers in Pharmacology, December 2020

    Case 1: Impending central retinal vein occlusion following COVID-19 pneumonia

    This report presents a patient presenting with multiple scotomas and decreased vision in the setting of a medical history of COVID-19.

    Case report details

    This report describes a 54-year-old female with prior history of COVID-19 who presented to the emergency department complaining of a 36-hour history of multiple scotomas and decreased vision in her right eye. Her neurological examination was normal apart from a relative afferent pupil defect (mildly positive on the right), the Pulfrich Test (mildly positive on the right) and the perception of color saturation which was decreased in the right compared with the left. Visual evoked potentials highlighted a relatively reduced amplitude of about 40% on the right compared with the left eye. A complete ophthalmological examination was not possible at presentation because of the pandemic. In the suspect of optic neuritis in the right eye and in consideration of a history of mild COVID-19 pneumonia, the patient was admitted and intravenous methylprednisolone 1 g/day was started.

    The following day, the patient underwent complete ophthalmological examination revealing visual acuity 20/40 in the right and 20/20 in the left. Funduscopic examination of the right eye revealed multiple retinal hemorrhages, increased venular tortuosity and a diffuse fern-like retinal whitening consistent with a diagnosis of impending central retinal vein occlusion (CRVO). Spectral-domain OCT revealed a hyperreflectivity of the inner retinal layers. The absence of focal thickening of the retinal nerve fiber layer and the preservation of the organization of the retinal layers allowed the authors to distinguish the retinal whitening from cotton wool spots and viral retinitis, respectively. Autofluorescence highlighted the typical distribution of the retinal alteration showing perivenular hypo-autofluorescence. A delayed arteriovenous transit time on fluorescein angiography confirmed the diagnosis of impending CRVO; excluding the optic neuritis.

    According to the revised diagnosis, steroid treatment was tapered to oral prednisolone 60 mg/day. Three days later multimodal imaging showed a minimal improvement of the retinal manifestations. Prednisolone was further decreased to 30 mg/day and the patient was discharged to quarantine. One week later, the patient's vision returned to 20/20 in both eyes and multimodal imaging revealed almost complete regression of the retinal alteration. The steroid treatment was slowly tapered with the plan to stop it within a month.

    Case 2: Central retinal artery occlusion following a severe course of COVID-19

    This report details a patient presenting with painless vision loss in the setting of a medical history of COVID-19.

    Case report details

    One week after discharge from the hospital for a severe course of COVID-19, a 59-year-old male with a history of hypertension and hyperuricemia presented with painless vision loss in the left eye. The patient noticed a decrease in visual function during his neuro-rehabilitation stay, but did not realize how severe it was until he covered the right eye the day before.

    On examination, BCVA was 20/20 in the right and light perception in the left. Examination of the left eye showed a nonreactive mydriasis and dilated funduscopic exam revealed severe arterial narrowing, retinal whitening in the macular region with loss of the physiological macular reflex and peripheral areas of retinal pigment epithelium hyperpigmentation. OCT indicated bilateral temporal macular thinning and severe atrophy of the inner retina layers with loss of the foveal depression in the left eye leading to a diagnosis of central retinal artery occlusion (CRAO).  The diagnosis was confirmed by fluorescein angiography that showed severe delay in the filling of the retinal arteries and a delayed arteriovenous transit time. In addition, findings consistent with sickle cell retinopathy were noticed, including areas of peripheral capillary nonperfusion, arteriovenous anastomoses and neovascular “sea-fans.” Blood tests with hemoglobin electrophoresis confirmed the presence of heterozygous hemoglobin S (sickle cell trait), while the inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) were within normal limits and not suggestive of an arteritic CRAO. At the 1-month follow-up visit, vision in the left eye improved to counting fingers and the left pupil was still nonreactive. OCT scans confirmed the loss of the foveal depression and showed ganglion cell layer atrophy.

    The patient had been hospitalized for COVID-19 requiring intubation for 10 days, 5 of which were with prone positioning, and he was later transferred to a neuro-rehabilitation department for physical deconditioning and mental confusion after the exclusion of cerebral ischemic events with computed tomography angiography of the cerebral arteries and magnetic resonance imaging of the brain.


    In the first case, the patient had no common risk factors for venous occlusion; it is likely that COVID-19 induced a transient hypercoagulability state leading to the impending CRVO; or hypoxia, which the patient may have experienced due to pneumonia, may have induced endothelial cells to release tissue factor, triggering the extrinsic coagulation pathway.  Even though it is not possible to definitively state the impending CRVO was directly caused by COVID-19, the development of an impending CRVO in a patient without any risk factors other than the transient hypercoagulability combined with the positive effect of the concomitant steroidal treatment on the inflammatory/coagulation status and the known high incidence of thromboembolic events in COVID-19 patients, suggest a possible correlation between systemic COVID-19 and the impending CRVO in this case.

    In the second case, the authors hypothesized that the induction of a prothrombotic vascular endothelial microenvironment by SARS-CoV-2 could be a precipitating factor causing the development of a CRAO, similar to what has been observed in other organs such as myocardial and renal microvasculature. COVID-19 has been described to predispose patients to thromboembolic disease in both venous and arterial circulation due to excessive inflammation from a "cytokine storm," endothelial dysfunction, platelet activation, stasis, hypoxia, immobilization and disseminated intravascular coagulation. A limitation is that, incidentally, the patient was diagnosed with sickle cell disease, and this condition could elicit retinal vascular occlusions. However, these occlusions occur predominantly in small-caliber peripheral arterioles and its association with CRAO is rare. Furthermore, retinal vascular damage could be correlated to the ocular expression of the angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is internalized by human cells after binding with the ACE2, which acts as a functional receptor for the virus. The expression of ACE2 has been detected in human aqueous humor and in retinal tissue, particularly in pigmented epithelial cells, photoreceptors and Müller cells. ACE2 plays an important role in vasoprotection. COVID-19 patients show a depletion of ACE2 function directly following the binding with SARS-CoV-2 and indirectly via shedding and proteolytic processing. ACE2 deficiency in animal models is associated with profibrotic and proinflammatory microvascular dysfunction and retinal nerve fiber layer infarcts.  

    Clinical significance

    These case reports are part of growing evidence that demonstrate that COVID-19 may cause a hypercoagulable state leading to retinal arterial occlusion, retinal venous occlusion and ophthalmic artery occlusion. Both hospitalized and ambulatory COVID-19 patients are at high risk for ocular microvascular complications. Patients with a systemic disease such as COVID-19 may underestimate their ocular symptoms. Therefore, physicians treating COVID-19 patients should consider paying close attention to symptoms and signs of possible ocular thromboembolic complications including painless acute vision loss, scotomas, decreased vision and blurry vision. Ophthalmologists and other clinicians should have a high index of suspicion for retinal vascular occlusions in patients presenting with decreased vision or blurry vision with a history of COVID-19 infection as prompt intervention may prevent irreversible visual loss.

    The association between COVID-19 with subsequent vascular occlusions has been described in other publications, including:

    The study describes a case of ophthalmic artery occlusion in a 48-year-old male with severe COVID-19 who complained of the sudden onset of painless vision loss in the right eye while on therapeutic anticoagulation with apixaban for deep venous thrombosis.

    This study describes a case of CRVO after COVID-19 infection in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after testing positive for SARS-CoV-2.

    This study describes a case of CRAO in a 60-year-old male who complained of the sudden onset of painless loss of vision in the right eye on the twelfth hospital day of a course of severe COVID-19 requiring intubation.