Author: Fatma Sümer (Turkey)
Co-authors: Vildan Sonalcan, Kübra Özata Gündoğdu
Abstract Purpose: To report a case of impending central retinal vein occlusion (iCRVO) in a COVID-19 patient. Case report: A 48 years old male with COVID-19 related pneumonia presented to the emergency department with scotoma and decreased vision complaints. The funduscopic examination and multimodal imaging revealed retinal hemorrhages, retinal whitening, and fern-like hypo-autofluorescent appearance typical to iCRVO in the left eye. He had no previous history of systemic risk factors other than a transient hyper-coagulability status likely related to the ongoing infection. Conclusions: Retinal circulation should be considered as a potential site for thromboembolic complications of COVID-19. The patient was diagnosed as RVO secondary to COVID 19 and underwent intravitreal ranibizumab injections (0.5 mg/0.05 mL) twice. Elevated coagulation parameters should be carefully evaluated in COVID-19 patients to avoid microvascular complications even in those with no previous risk factors. Keywords: Covid-19; central vein occlusion; retina; thrombosis
Coronavirus disease (CD) broke out in China and was described as an epidemic by the World Health Organization (WHO) on March 11, 2020. While severe symptoms do not occur in most of the patients, 10-20% of the patients with the disease may experience interstitial pneumonia with acute respiratory distress and result in death. The immune system response of the host plays an active role in the severity of the clinical presentation. It was reported that the most common severe findings of COVID-19 were lymphopenia, high acute phase reactants, and cytokine irregularity. Moreover, COVID-19 was also related to coagulation impairment such as hypercoagulation, D-Dimer elevation, prolonged PT and aPTT, and fibrin disorders.  Although systemic macrovascular thromboembolic complications related to COVID-19 were previously reported, there is still a lack of knowledge about microvascular complications of the infection such as retinal vessel occlusions. Retinal vein occlusions are commonly accompanied by various systemic disorders, particularly in patients over 60 years old.  Besides, COVID-19 may aggravate the classical Virchow triad for thrombogenesis, including vessel damage, stasis, and hypercoagulability. Although few central retinal vein occlusion (CRVO) cases related due to COVID-19 were previously reported, they were observed in elder patients who had accompanying conditions such as hypertension, hypercholesterolemia, or diabetes. This paper reports a CRVO case due to COVID-19 in a fairly young patient with no previous systemic disease history. Hence, it is aimed to emphasize the microvascular involvement of COVID-19 as a part of systemic thromboembolic complications of the disease.
A 48 years old male presented to the emergency department with visual symptoms that initiated in the last 72 hours. Besides, the patient suffered fatigue, muscle pain, headache, and relapsing fever complaints in the last 10 days. His COVID-19 nasopharyngeal swab PCR test was detected positive 6 days ago. His temperature was 37.3°C, blood pressure was 135/85 mmHg, pulse was 88 bpm, respiratory rate was 14 breaths per minute, and oxygen saturation was 98%. Complete blood count (CBC), coagulation, and inflammatory markers were evaluated and chest x-ray imaging was performed. In the biochemical blood analysis; C-reactive protein (CRP) was 33.4 mg/L (normal value <10.0 mg/L), erythrocyte sedimentation rate was 87 (normal value <30), lactate dehydrogenase was 272 U/L (normal range 125–220 U/L), PT was 15.8 sec, I.N.R. was 1.27, (normal range 0.85–1.18), aPTT 37.3 sec, Ratio 1.26, (normal range 0.85–1.2), fibrinogen was 6.93 g/l (normal range 1.70–4.00 g/l) and D-dimer was 414 µg/L fibrinogen equivalent units. Other blood parameters including CBC, creatinine, bilirubin, glucose, electrolytes, and creatine kinase were within normal limits. Chest x-ray imaging demonstrated bilateral diffuse thickening of the interstitial structure and multiple opacities with ground-glass appearance. The patient was diagnosed with mild COVID-19-related pneumonia. The patient was immediately consulted with the Ophthalmology department due to his acute vision loss. Snellen’s corrected distance visual acuity (CDVA) was 6/6 OD and 6/60 OS. Biomicroscopic anterior segment evaluation was normal. However, dilated fundoscopy revealed unilateral optic disc swelling with splinter hemorrhages, and multiple flame-shaped and blot hemorrhages in all retinal quadrants of the left eye. [Fig. 1a and b]. Spectral-domain optical coherence tomography (SD-OCT) of the left eye demonstrated the presence of serous macular detachment [SMD]. and significant cystoid macular edema (CME), with cysts located in the outer nuclear layer. [Fig. 2] Fundus fluorescein angiography (FFA) revealed dilated and tortuous retinal veins at the inferior quadrant of the left eye. [Fig. 3]. Hypofluorescent areas were noted at the affected retinal quadrants that clinically corresponded with hemorrhages, leading to blocked fluorescence. The patient was diagnosed with left inferior hemi-retinal vein occlusion and macular edema. The RVO developed secondary to COVID 19 and the patient underwent two intravitreal anti-vascular endothelial growth factor (anti-VEGF) ranibizumab 0.5 mg/0.05 mL (Lucentis PFS, Novartis, Basel, Switzerland) injections at onset and after 4 weeks. The CDVA improved to 6/9 at the 8th-week visit and no SMD and/or CME was observed in SD-OCT. [Fig. 4] Therefore, the intravitreal injection was halted and the patient is still followed by monthly visits.
COVID-19 is an enveloped, non-segmented positive-sense RNA virus from the newly identified Coronaviridae family.  Today, it is mostly associated with atypical pneumonia and acute respiratory failure, and the most common complication among ocular complications is conjunctivitis. However, Marinho et al. identified retinal vascular abnormalities associated with COVID-19. Virchow's triad (hypercoagulation, endothelial damage, and stasis), which occurs in systemic thrombotic events, may also take part in microvascular thrombosis.  Therefore, the presence of any of these three conditions may increase the risk for retinal vessel occlusions. Our case report describes a young patient with CRVO without any comorbid diseases or systemic disorders such as diabetes, hypertension, and tuberculosis. In differential diagnosis, vasculitis should be excluded and this patient had no sign of vasculitis in the retinal examination. Therefore, we considered a hypothetical diagnosis as vasculitic-CRVO secondary to COVID-19. Two separate hypotheses were proposed to explain the vascular damage due to COVID-19: the first is the pseudo-vasculitic condition caused by viral infiltration of vascular endothelial cells, and the latter is hypercoagulation, similar to disseminated intravascular coagulation. (DIC). In this case, the high coagulation parameters of the patient point to the DIC-like situation rather than a pseudo-vasculitic situation caused by COVID-19. Besides we did not detect any finding in laboratory tests indicating a cytokine storm caused by COVID-19 infection. Previous reports demonstrated foveolitis, retinitis, neuroretinitis, optic neuritis, and panuveitis in viral infections caused by the direct viral involvement or a delayed immune response to the viral antigens. [7,8] Those were more likely to occur by immune-mediated pathogenesis than direct viral involvement, considering the posterior segmental involvement 1-4 weeks after the onset of the disease.  In our case, the 6-day time difference between the acute infection and the retinal findings and ocular complaints may also better explain the role of immune complex accumulation in pathogenesis. As a conclusıon, microvascular occlusion may occur, as in our case, due to the increased coagulation parameters in COVID-19 infection. This should be taken into consideration in COVID-19 patients even in those with no previous history of systemic risk factors. A systematic meta-analysis of the case reports in the future may shed light on the possible mechanisms of the retinal vascular complications of the disease.
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None of the authors have competing interest related to the paper