Retrospective diagnosis of COVID-19 following the detection of central retinal artery occlusion.

Thromboembolic complications are being increasingly reported in patients with COVID-19 due to the associated hypercoagulability and are an important cause for morbidity and mortality. Retinal vascular occlusions especially arterial occlusions are one of the gravest ocular complications reported. This complication may occur in severe cases with cytokine storm or even in mild or asymptomatic patients and presentation can be anytime from few days to weeks after the onset of symptoms. Ophthalmologists should be aware of this new etiology when dealing with patients having features of retinal vascular occlusions and should investigate for the same in this pandemic situation. Although reverse transcriptase polymerase chain reaction is the diagnostic test for COVID-19, serological assays have a role in patients with delayed presentation. We describe the clinical features and multimodal imaging findings in a patient who presented with features of central retinal artery occlusion with cilioretinal artery sparing wherein his ophthalmic condition led to the diagnosis of previously undetected COVID-19 through serology. To the best of our knowledge, this is the first documentation of a case of isolated central retinal artery occlusion leading to a retrospective diagnosis of COVID-19. Copyright:

Introduction

COVID-19, a pandemic disease caused by severe acute respiratory syndrome virus 2 is found to cause a hypercoagulable state leading to a spectrum of thromboembolic events involving multiple organs.[1] Retinal vascular occlusions especially arterial occlusions are one of the gravest ocular complications reported. We describe a patient who presented with features of central retinal artery occlusion (CRAO) wherein his ophthalmic condition led to the diagnosis of COVID-19, which was previously undetected.

Case Report

A 47-year-old male with diabetes and congenital heart disease presented in April 2021 with sudden painless visual loss in the right eye (RE) of 3 weeks’ duration. He gave history of fever and body ache 5 days before the visual loss. As he was working abroad, he could not undergo any consultation but reverse transcriptase polymerase chain reaction (PCR) for COVID-19 done 2 weeks later was negative. He returned to India and PCR was done on arrival and after 2 weeks of quarantine were negative. He was not vaccinated for COVID. On examination, his best corrected visual acuity was 6/36, N.36 in the RE and 6/6, N.6 in the left eye (LE). There was relative afferent pupillary defect in the RE. Slit-lamp examination and applanation tension were unremarkable. Fundus of the RE showed disc pallor, arteriolar attenuation, foveal cherry red spot, retinal whitening with a small sector of perfused retina indicating CRAO with cilioretinal artery (CLRA) sparing, while the left fundus was normal [Figure 1]. Both eyes had no diabetic retinopathy. Optical coherence tomography (OCT) revealed hyper reflectivity of the inner retinal layers in the area of whitening and normal reflectivity over the perfused retina confirming the clinical diagnosis [Figure 2a]. Humphrey visual fields examination revealed a small island of vision contributed by the perfused retina [Figure 2c]. Fundus autofluorescence imaging revealed hypo-autofluorescence with relative hyper autofluorescence temporal to disc [Figure 3a]. OCT angiography revealed extensive capillary drop out except in the zone perfused by the CLRA [Figure 3b]. Multimodal imaging of LE was normal [Figure 2b and d]. Subsequent cardiology evaluation detected asymptomatic aortic stenosis and he was prescribed antiplatelets and statins. Neurological evaluation including imaging was normal. His hemogram, erythrocyte sedimentation rate, blood sugar, lipid profile, renal function tests, and serum homocysteine were also normal. However, immunoassay of IgG antibody for COVID-19 revealed a positive titer of 68.5 AU/ml (lab reference normal being <15).

Figure 1

Wide-field color fundus photo of both eyes: Right eye (a) has disc pallor, attenuated arterioles, foveal cherry red spot with retinal whitening sparing a small sector adjacent to disc with patent cilioretinal artery (arrow). Left eye (b) is normal with no diabetic retinopathy

Figure 2

Optical coherence tomography and Humphrey visual fields (central 30-2 threshold test) of both eyes: Right eye optical coherence tomography (a) shows hyperreflectivity with indiscernible inner retinal layers and abrupt transition into normal reflectivity nasally. Right eye field (c) is grossly constricted sparing a small paracentral island. Optical coherence tomography and fields of the left eye (b and d) is normal

Figure 3

Fundus autofluorescence imaging and optical coherence tomography angiography of the right eye: Fundus autofluorescence (a) clearly delineates the hypo-autofluorescent edematous retina from the hyper-autofluorescent perfused retina around the cilioretinal artery. Optical coherence tomography angiography at the level of deep vascular complex (b) demonstrate the extensive capillary drop out sparing the zone perfused by cilioretinal artery

Discussion

Retinal arterial occlusions are usually secondary to embolism from carotid atheromas or cardiac emboli and rarely due to hypercoagulable states and vasculitis.[2] Another relevant etiology would be COVID-19 as it is now being understood as a thromboembolic disease. Landecho et al. has suggested retinal microangiopathy as an in vivo biomarker of COVID-19.[3] The vascular damage could be due to disseminated intravascular coagulation like hypercoagulable state or due to direct viral infection of endothelial cell and diffuse endotheliitis. The other retinal vaso-occlusive events reported range from paracentral acute middle maculopathy and acute macular neuroretinopathy to papillophlebitis, ophthalmic artery occlusion, retinal arterial, and venous occlusions.[4] Acharya et al. reported a case of isolated CRAO in an elderly patient with multiple co-morbidities and COVID-19 cytokine release syndrome.[1] Literature search revealed two other reports of CRAO in COVID-19 patients, one by Montesel et al. in a 59 years old male with hypertension and sickle cell disease and the other, a case of bilateral CRAO in a young male with no comorbidities by Bapaye et al.[56] All were PCR confirmed COVID-19 cases and despite receiving appropriate systemic therapy, developed the complication. These cases highlight the thrombogenicity of the virus and the vulnerability of retinal circulation to vaso-occlusive events.

In our patient, visual loss was preceded by systemic symptoms suggestive of COVID-19, but was not confirmed because PCR was done only 2 weeks later. His serial negative PCRs ruled out disease at the time of testing but not past illness. To detect a past infection serology was done, which revealed high titer confirming our clinical suspicion. His unvaccinated status also supports this possibility. IgG serological assays have a sensitivity >80% and specificity of >97% when done more than 2 weeks after the onset of symptoms.[7] Though he is a diabetic, his glycemic control was good and he had no microvascular complications as evidenced by the lack of diabetic retinopathy and normal renal parameters. The preexisting aortic stenosis could be a possible risk factor for CRAO but in the present scenario, it is more likely that COVID-19 would have precipitated it. The comorbidities would have probably increased the risk of vascular occlusion in this patient with COVID-19. Detailed inflammatory work up was not done as he had already recovered from the illness. To the best of our knowledge, this is the first documentation of a case of isolated CRAO leading to a retrospective diagnosis of COVID-19 through serology. Though useful in identifying such delayed presentation, serology has a limitation in vaccinated patients. Murchison et al. has reported a case of CRAO with CLRA sparing secondary to internal carotid artery thrombosis in a hypertensive male who presented with monocular visual loss.[8] He had mild pharyngitis and diarrhea 3 days prior to visual loss. As per the hospital's policy in acute cerebrovascular event, patient underwent PCR for COVID-19 and was confirmed positive. Both these patients were asymptomatic, undetected cases and it was the ocular condition that led to the diagnosis of COVID-19. Thus, retinal vascular complications may occur in severe cases with cytokine storm or even in mild or asymptomatic patients and presentation can be anytime from few days to few weeks after the symptom onset.[4] Ophthalmologists should be aware of this association and COVID-19 should be included in the work up for retinal vascular occlusions.

Conclusion

A possible association with pandemic infection should be suspected in all patients presenting with vascular occlusions and should be evaluated for the same. PCR is the diagnostic test in acute situation, but in those undetected cases presenting in the delayed phase serology is useful to establish a diagnosis. Such patients can then be evaluated for delayed thromboembolic complications of COVID-19, the major cause for systemic and ocular morbidity and even mortality.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.