Central Retinal Vein Occlusion in a Young Healthy COVID-19 Patient: A Case Report and Literature Review.

Coronavirus disease (COVID-19) has been declared by the World Health Organization as a pandemic on March 11, 2020. COVID-19 predispose patients to multisystem thromboembolic events, including pulmonary emboli and deep vein thrombosis. We report a 33-year-old previously healthy man, with previous history of COVID-19 infection presented with left eye central retinal vein occlusion (CRVO) with secondary macular edema. All possible risk factors for thromboembolic events were excluded. After a single dose of intravitreal injection of aflibercept (2 mg in 0.05 ml), gradual improvement in the clinical manifestation of CRVO with complete resolution of macular edema in the left eye was observed. To the best of our knowledge, this is the first report of CRVO post-COVID-19 in Oman. Copyright:

Introduction

Coronavirus disease (COVID-19), has been declared by the World Health Organization as a pandemic on March 11, 2020.[1] The most common symptoms of COVID-19 include fever, dyspnea, dry cough, and loss of smell and taste. The progression of the disease could lead up to acute respiratory distress syndrome, septic shock, and multi-organ failure.[2] The pathogenesis of this severe acute respiratory syndrome (SARS) virus continues to be poorly understood. Among those treated COVID-19 patients, the SARS-CoV-2-induced cytokine storm is a recognized cause of morbidity and mortality and a growing collection of data supports COVID-19 predisposing patients to thromboembolic events with a multitude of systemic adverse effects, including pulmonary emboli and deep vein thrombosis.[34] SARS-CoV-2 affects different organs such as lungs, kidneys, and eyes. From ocular perspective, ophthalmic associations have been reported such as; conjunctivitis, retinal microvascular changes such as retinal microangiopathy, cotton wool spots and microhemorrhages.[567] In addition, paracentral acute middle maculopathy, acute macular neuroretinopathy, and papillophlebitis have been reported in COVID-19 patients.[89]

Retinal vein occlusion (RVO) is commonly associated with older age patients with known risk factors such as hypertension, atherosclerosis and diabetes mellitus and others. In central retinal vein occlusion (CRVO), sudden visual loss is the most common presentation, with severity ranging from mild (in nonischemic type) to severe (in ischemic type).[10] The occurrence of CRVO among individuals under 50 years of age is considered to be rare and has been reported to be <1.5 cases per year at a single institution, or 0.93 per 1000 among persons under 64 years of age.[11] In such young age group, thorough systemic work up is recommended and the management of the underlying systemic cause is crucial. We report a young patient with CRVO post-COVID-19 infection.

Case Report

A 33-year-old healthy man, who had a history of COVID-19 infection 6 months ago (October 2020), was referred to Sultan Qaboos University Hospital with 1-week history of painless blurring of vision in the left eye. As per patient, the visual symptoms started 2 h after he received one dose of COVID-19 vaccine (Pfizer-BioNTech). No personal or family history of thromboembolism. On examination, he is mildly obese (weight 123 Kg), visual acuity was 1.0 both eyes, and intraocular pressure was 9 mmHg both eyes. Anterior segment examination was normal in both eyes. The right eye fundus examination was unremarkable [Figure 1a]. Dilated fundus examination of left eye [Figure 1b] showed optic disc swelling, diffuse intraretinal hemorrhages in all four quadrants, vascular touristy, cotton wool spots in the inferior and superior temporal arcades. Optical coherent tomography (OCT) macula revealed normal central macula thickness in the right eye [Figure 1c] and increased central macular thickness with intraretinal and subretinal fluid in left eye [Figure 1d].

Figure 1

Color fundus photos and optical coherent tomography macula at presentation: (a) Right eye shows normal fundus. (b) Left eye shows optic disc swelling, diffuse intraretinal hemorrhages in all four quadrants, vascular tortuosity, cotton wool spots in the inferior and superior temporal arcades. (c) Optical coherent tomography macula of right eye shows normal central macula thickness. (d) Optical coherent tomography macula of left eye shows increased central macular thickness with intraretinal and subretinal fluid

The patient underwent thorough hematological workup, all thrombotic work up were negative [Table 1]. In particular, there was no evidence of inherited thrombophilia (protein C and S deficiencies, anti-thrombin deficiency, factor V Leiden mutation or prothrombin gene G20210A mutation). He also tested negative for antiphospholipid syndrome, vasculitis, and myeloproliferative neoplasms. Due to the remote possibility of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT), we tested him for heparin-induced thrombocytopenia (HIT) which came as negative. VITT is a rare but potentially life-threatening prothrombotic complication of COVID-19 vaccines.[12] It has been described in adenovirus-vectored vaccines such as ChAdOx1 nCoV-19 (AstraZeneca/Oxford) vaccine.[1314] VITT has not been described in mRNA vaccines such as Pfizer-BioNTech vaccine. The patient was started on Rivaroxaban 15 mg every 12 h for 3 weeks followed by 20 mg once daily thereafter.

Table 1

Summary of hematological workup

Test	Result	Normal range
Hemoglobin (g/L)	15	11.5-14.5
Hematocrit (L/L)	0.459	0.350-0.450
Platelet count (109/L)	321	150-450
White cell count (109/L)	5.2	2.2-10
PT (s)	10.2	9.8-12
APTT (s)	33.8	25.0-36.4
Fibrinogen (g/l)	4.4	1.7-3.6
D-dimer (mg/L FEU)	0.2	0.2-0.7
CRP (mg/L)	4	0-5
eGFR (ml/min/1.73 m2)	>90	>90
Antithrombin functional (IIa inhibition 20 s) (u/ml)	0.917	0.880-1.220
Antithrombin functional (Xa inhibition) (u/ml)	0.906	0.890-1.280
Protein C functional chromogenic (u/ml)	1.128	0.720-1.540
Protein C functional clotting (u/ml)	1.124	0.800-1.810
Protein S function (u/ml)	>1.26	0.720-1.450
Free protein S antigenic (u/ml)	1.197	0.675-1.390
Factor VIII chromogenic assay (u/ml)	1.107	0.580-1.880
HIT ELISA (Asserachrom HPIA IgG assay; Diagnostica Stago)	Negative
Lupus anticoagulant	Not detected
Antiphospholipid antibodies	Not detected
Factor V Leiden result	Normal
Prothrombin II G20210A Result	Normal
ANA	Negative
ENAs	Negative
JAK2 V617F mutation	Not detected
JAK2 exon12-14 mutation	Not detected
CALR exon 9 mutation	Not detected

ANA: Anti-nuclear antibody, ENAs: Extractable nuclear antigens, HIT ELISA: Heparin-induced thrombocytopenia (HIT) enzyme-linked immunoassay (ELIZA), HPIA: Heparin-Platelet Factor 4-Induced Antibody, PT: Prothrombin time, aPTT: Activated partial thromboplastin time, CRP: C-reactive protein, eGFR: Estimated glomerular filtration rate

Two weeks later, the patient received intravitreal injection of aflibercept (Eylea) 2 mg in 0.05 ml in the left eye elsewhere. Four weeks later, the patient was symptomatically much better with visual acuity remained 1.0 in both eyes. Dilated fundus of the right eye remained normal [Figure 2a] and left eye showed residual mild optic disc swelling, vascular touristy, and cotton wool spots [Figure 2b]. OCT macula shows normal central macula thickness in both eyes with complete resolution of the left eye macular edema [Figure 2c and d] and normal retinal superficial macular capillary plexus in both eyes [Figure 2e and f].

Figure 2

Color fundus photos and optical coherent tomography/angiography (OCT/A) macula at 4 weeks follow up visit: (a) Right eye shows normal fundus. (b) Left eye shows residual findings of mild optic disc swelling, vascular touristy and cotton wool spots. (c and d) Optical coherent tomography macula shows normal central macula thickness in both eyes with complete resolution of left eye macular edema. (e and f) Optical coherent tomography/angiography shows normal superficial macular capillary plexus in both eyes

Discussion

We report a young man who had a mild course of COVID-19 infection on October 2020. In April 2021 he received one dose of COVID-19 vaccine (Pfizer-BioNTech), 2 h after the vaccine he noticed left eye blurring of vision and found to have left eye nonischemic CRVO. In our patient all possible risks for CRVO including COVID-19 VITT were excluded. VITT as the cause of the CRVO in our patient was excluded given the normal platelets count, normal D-dimer, and negative HIT enzyme-linked immunosorbent assay. Furthermore, our patient received Pfizer-BioNTech vaccine, and VITT has not been described to be associated with this vaccine. Moreover, the very short time between the vaccine and the symptoms make it very unlikely that the vaccine is a contributing cause to the CRVO.

The only possible remaining risk for CRVO is previous infection with COVID-19. RVOs post-COVID-19 were recently reported in the literature.[1516] However, to the best of our knowledge, this is the first reported case of CRVO associated with previous infection with COVID-19 in Oman.

Yahalomi et al. reported a 33-year-old healthy male who developed left eye CRVO 3 weeks' post-COVID-19 infection. After which he showed complete resolution of symptoms and gradually improvement of the retinal vascular appearance.[15] Gaba et al. reported a 40-year-old man, known case of controlled hypertension and obesity, presented with 3 days' history of shortness of breath, fever, cough, and pain in his right calf. SARS-CoV-2 was confirmed and a high-resolution computed tomography scan of the chest showed features of severe COVID-19 pneumonia. The patient was admitted with impression of pulmonary embolism in the context of DVT and COVID-19. He was started on a therapeutic dose of low-molecular-weight heparin (LMWH). On day 2 of admission, the patient complained of painless blurred vision in both eyes. Ophthalmology examination revealed bilateral CRVO. The patient's condition improved during admission and the LMWH was switched to rivaroxaban, 15 mg twice daily for 21 days than 20 mg once daily for 3 months during which patient's condition improved and had near normal vision.[16] Walinjkar et al. reported a 17-year-old girl with right eye CRVO associated with of COVID-19. The patient was given intravitreal injection of ranibizumab (0.5 mg/0.05 ml) after which significant resolution of CRVO signs were observed.[17]

Conclusion

In this case report, we shared a possible association between COVID-19 and unilateral CRVO in a young healthy gentleman. Patients and eye caregivers should be aware about ophthalmic associations with COVID-19. Patients with visual complaints during or post COVID-19 should be assessed by ophthalmologist. To the best of our knowledge, this is the first report of CRVO post-COVID-19 in Oman.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.