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Vol. 221. Issue 10.
Pages 587-591 (December 2021)
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Vol. 221. Issue 10.
Pages 587-591 (December 2021)
Brief Original
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Effects of the COVID-19 pandemic on a cohort of patients with vein occlusion
Efectos de la pandemia por SARS-CoV-2 en una cohorte de pacientes con obstrucción venosa retiniana
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J.D. García Palaciosa,
Corresponding author
jdavidgarciapalacios@gmail.com

Corresponding author.
, N. Puente Ruiza, J.J. Napal Lecumberria, J.L. Hernández Hernándeza,b
a Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Cantabria, Spain
b Universidad de Cantabria, Santander, Cantabria, Spain
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Tables (2)
Table 1. Principal epidemiological characteristics of patients with RVO and COVID-19.
Table 2. Characteristics of COVID-19 in patients with RVO.
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Abstract
Background and objectives

A new coronavirus disease in humans, COVID-19, caused by SARS-CoV-2, emerged in December 2019. It has been associated with the development of thrombotic phenomena. Retinal vein occlusion (RVO) is mainly a consequence of vascular risk factors (VRF). This study aimed to analyze cases of COVID-19 in a cohort of patients with RVO (Valdecilla cohort).

Patients and methods

Between December 2008 and December 2020, 429 patients with RVO were attended to in our clinic. Ten patients had COVID-19, one of which did not have VRF or thrombophilia. The remaining nine patients had RVO prior to the infection and VRF, six had carotid atherosclerosis, and four had antiphospholipid syndrome. The infection did not cause thrombotic phenomena in any of them.

Conclusions

RVO is a rare manifestation of COVID-19. In our cohort of patients with RVO, COVID-19 disease did not lead to thrombotic events.

Keywords:
COVID-19
Retinal vein occlusion
Vascular risk factors
Thrombophilia
Resumen
Antecedentes y objetivos

En diciembre de 2019 surgió una nueva enfermedad por coronavirus en humanos causada por el virus SARS-CoV-2, la COVID-19, que se ha asociado con fenómenos trombóticos. La obstrucción venosa retiniana (OVR) es principalmente una consecuencia de los factores de riesgo vascular (FRV). El objetivo de este estudio ha sido analizar los casos de infección por SARS-CoV-2 en una cohorte de pacientes con OVR (cohorte Valdecilla).

Pacientes y métodos

Entre diciembre de 2008 y 2020 hemos atendido 429 pacientes con OVR. Diez han padecido COVID-19, de los que uno no presentaba FRV ni trombofilia. Los otros 9 fueron diagnosticados de OVR antes de la infección: todos tenían FRV; 6 ateromatosis carotídea y 4 presentaban un síndrome antifosfolípido. La infección no causó en ellos fenómenos trombóticos.

Conclusiones

La OVR es una manifestación infrecuente de la COVID-19. En nuestra cohorte de pacientes con OVR la COVID-19 no indujo eventos trombóticos.

Palabras clave:
COVID-19
Obstrucción venosa retiniana
Factores de riesgo vascular
Trombofilia
Full Text
Introduction

Retinal vein occlusion (RVO) is a consequence of vascular risk factors (VRF) and, to a lesser extent, thrombophilia1,2. Locally, glaucoma is a factor that favors onset of RVO in a central localization3.

The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, a pandemic in March 2020. The disease’s spectrum varies widely, from asymptomatic patients to others with severe pneumonia and respiratory distress syndrome4,5. As a result of the hyperinflammatory response which develops in severe cases, COVID-19 has also been associated with thromboinflammation and thrombosis, causing artery and vein occlusion, microinfarcts, and multiple organ failure6. Retinal vascular involvement due to COVID-19 is rare, with five cases described in the literature7–10; one of these cases was in Spain11.

Aim

This work aims to analyze cases of SARS-CoV-2 infection in a cohort of patients with RVO during the first and second waves of the pandemic (March to December 2020).

Patients and methods

All patients in our healthcare area who were diagnosed with RVO were referred to the internal medicine clinic for study (Valdecilla cohort), where diagnosis, optimization, treatment, and follow-up on VRF and thrombophilia were conducted.

The Valdecilla cohort study was conducted in the Marqués de Valdecilla University Hospital in Santander, Spain, a tertiary hospital with a reference population of 350,000 inhabitants. The Ethics Committee of Cantabria (2019.340) approved the study and subjects signed informed consent forms in order to participate.

From December 2008 to December 2020, 429 patients with RVO were treated. Forty of them died before the start of the pandemic (March 2020). From the first cases of SARS-CoV-2 infection to the end of the second wave, ten patients from the Valdecilla cohort had COVID-19.

Clinical variables

The clinical variables recorded were differentiation between central or branch RVO (temporal or nasal); presence of hypertension (blood pressure ≥140 and/or 90 mmHg or receiving antihypertensive drug treatment); diabetes mellitus (according to the American Diabetes Association criteria)12; dyslipidemia (total cholesterol or triglycerides >230 and >150 mg/dL, respectively, in at least two measurements after a 24 h fasting period or receiving lipid-lowering treatment); and presence of genetic or acquired thrombophilia.

Laboratory determinations

A routine biochemistry profile, including a lipid panel, was conducted with an Advia® 2400 (Siemens) autoanalyzer. Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and β2-glycoprotein I) were measured in all patients. A diagnosis of antiphospholipid syndrome was established according to the guidelines of the International Society on Thrombosis and Haemostasis13. Whenever there was a positive antibodies result, a second measurement was performed at 12 weeks; if the lupus anticoagulant was positive and/or the anticardiolipin antibody and/or β2-glycoprotein I titers were in intermediate or high ranges on the second measurement, it was considered positive. In those whose results were not conclusive, a third measurement was conducted 12 weeks later.

A genetic thrombophilia study (prothrombin gene, factor V Leiden, protein C, protein S, antithrombin) was conducted in all patients from December 2008 to December 2015. Later, given that this thrombophilia only plays an important role in subjects younger than 50 years of age or without VRF, it was only measured in this group of patients1.

Imaging tests

A Doppler ultrasound of the supra-aortic trunks was used to evaluate the presence of atheroma plaques and quantify the degree of vascular stenosis. The study was conducted with a B-mode, color Doppler, and spectral Doppler ultrasound of the carotid and vertebral systems with a high-frequency linear probe (General Electric, Logiq® model).

Results

A total of 429 patients with RVO were treated in our clinic as of December 2020. Of them, 290 had peripheral RVO (284 temporal and six nasal) and 139 had central RVO. Of the 429, 40 had died before the start of the pandemic. Therefore, the study group comprised 389 patients.

The mean age was 67.9 ± 12.8 years. Nine patients in the cohort had already been diagnosed with RVO before the start of the pandemic and one developed peripheral RVO and glaucoma after COVID-19; the patient received treatment with oral deflazacort and timolol eye drops and progressed favorably. He presented with a fever of 38.5 °C for three days and headache, asthenia, and anosmia for one month. Laboratory tests were not performed. Vision changes appeared at three weeks following onset of fever. There were no changes observed in ophthalmologic follow-up appointments conducted after SARS-CoV-2 infection in the rest of the cases which had previously presented with RVO. In four cases, additional tests were conducted, including measurements of platelets (reference range: 150,000–450,000/μL), d-dimer (0–500 ng/mL), and fibrinogen (180–500 mg/dL); case 2: 109,000, 1302, and 541; case 3: 329,000, 2692, and 6000; case 4: 103,000, 487, and 766; and case 7: 279,000, 1327, and 815, respectively.

Table 1 shows the age, sex, RVO type, date of diagnosis, VRF (hypertension, dyslipidemia, diabetes mellitus), thrombophilia, presence of carotid atheromatosis, associated diseases, and prior treatment for each of the ten cases.

Table 1.

Principal epidemiological characteristics of patients with RVO and COVID-19.

Patient  Age (years)  Sex  Type of RVO (involvement)  Date of diagnosis  VRF  Thrombophilia- APLA- Genetic thrombophilia  Carotid atheromatosis (Doppler SAT)  Associated diseases  Treatment 
55  Woman  Temporal  May 2020  No  - Negative  No  Ankylosing spondylitis  Secukinumab 
            - Negative       
62  Woman  Central  October 2019  HT  - LA positive  Yes  SAHS  ASA, atorvastatin, LMWH 
          DLP  - Negative       
74  Man  Central  June 2013  HT  - LA positive  Yes  Liver Disease  ASA, valsartan, amlodipine, atorvastatin, ezetimibe, LMWH 
          DLP  - Negative    Peripheral artery disease   
82  Man  Temporal  April 2014  No  - Negative  Yes  No  ASA 
            - Negative       
83  Woman  Temporal  December 2018  HT  - Negative  Yes  No  ASA, olmesartan, amlodipine, gliclazide, atorvastatin/ezetimibe 
          DM  - NP       
          DLP         
62  Man  Central  April 2017  HT  - Negative  No  AF  Enalapril, atorvastatin, apixaban 
          DLP  - NP    Glaucoma   
77  Woman  Temporal  July 2018  HT  - Negative  Yes  RA  Olmesartan, atorvastatin 
          DLP  - NP    Advanced renal neoplasm   
90  Woman  Temporal  October 2018  HT  - LA positive  Yes  Hypothyroidism  Valsartan, ASA, atorvastatin, metformin, LMWH 
          DLP  - NP       
          DM         
62  Woman  Central  March 2015  DLP  - LA positive  No  Severe adjustment disorder  Rosuvastatin, LMWH 
            - Negative       
10  59  Woman  Central  December 2019  HT  - Negative  No  Osteopenia  Atorvastatin, ASA 
          DLP  - NP       

AF: atrial fibrillation; APLA: antiphospholipid antibodies; ASA: acetylsalicylic acid; DLP: dyslipidemia; DM: diabetes mellitus; HT: hypertension; LA: lupus anticoagulant; LMWH: low-molecular-weight heparin (in prolonged bedrest); NP: not performed; RA: rheumatoid arthritis; RVO: retinal vein occlusion; SAHS: sleep apnea-hypopnea syndrome; SAT: supra-aortic trunks; VRF: vascular risk factors.

Table 2 shows the date of COVID-19 diagnosis, the diagnostic technique (PCR or antibodies), symptoms, need for admission, and treatment.

Table 2.

Characteristics of COVID-19 in patients with RVO.

Patient  Date of diagnosis  Diagnostic method  Manifestations  Hospital admission/reason  COVID-19 treatment  de novo RVO 
04/15/2020  CRP  Fever, headache, dysgeusia, anosmia  No  No  Yes 
04/16/2020  CRP  Fever, dyspnea  Yes/left basal pneumonia  Lopinavir/ritonavir, hydroxychloroquine, ceftriaxone, enoxaparin  No 
03/20/2020  CRP  Fever  Yes/comorbidities  Hydroxychloroquine, enoxaparin.  No 
12/09/2020  CRP  Fever  No  Levofloxacin  No 
03/16/2020  CRP  Fever, dysgeusia, changes in smell  No  No  No 
05/10/2020  Antibodies (IgG+Asymptomatic  No  No  No 
09/17/2020  CRP  Asymptomatic  Yes/neoplasm  No  No 
10/06/2020  CRP  Asymptomatic  No  No  No 
03/27/2020  CRP  Asymptomatic  No  No  No 
10  09/18/2020  CRP  Fever, headache  No  No  No 

RVO: retinal vein occlusion; PCR: polymerase chain reaction.

Discussion

We found one patient with COVID-19 who developed RVO. In addition, we observed an absence of vascular events (including recurrence of RVO) after COVID-19 infection in nine patients with prior RVO (Valdecilla cohort). Cantabria has been one of the autonomous communities with a lower incidence of COVID-19: it had 17,896 total cases as of December 2020 and a cumulative incidence of around 3%14,15.

The patient with RVO, which was probably a consequence of COVID-19, was young. She did not have VRF and the thrombophilia study was negative. Although she had ankylosing spondylitis (AS) in treatment with secukinumab, the real effect of immunomodulators in COVID-19 is unknown; on the one hand, they can increase risk of infection, but on the other hand, they could protect against a hyperinflammatory storm. In a series of patients with AS treated with secukinumab, the majority presented with a mild form of COVID-1916.

Three of the five cases of RVO and COVID-19 described in the literature7–9 are similar to our case. They are young women (age: 33–55 years) without any VRF or thrombophilia who presented with unilateral RVO after COVID-19. The other two cases are bilateral RVO in patients between 30 and 40 years of age with VRF and severe COVID-19 pneumonia10,11.

It should be noted that in our cohort of patients with RVO, 90% had some VRF, 10% had antiphospholipid syndrome (APLS), 13% had genetic thrombophilia, and just 2% did not present with VRF or thrombophilia1,2,11.

In the nine patients who belong to the Valdecilla cohort, COVID-19 was not associated with the onset of new thrombotic phenomena and no new retinal abnormalities or worsening of RVO was observed on ophthalmologic follow-up appointments after SARS-CoV-2 infection. All had at least one VRF: six presented with carotid atheromatosis and four met the criteria for APLS. VRF were controlled in all subjects and in addition, six received treatment with acetylsalicylic acid, one with apixaban for atrial fibrillation, and low-molecular-weight heparin (LMWH) was recommended for the four diagnosed with APLS for whom prolonged bedrest was indicated. Although there are no randomized, controlled trials which demonstrate it, thromboembolic prophylaxis with LMWH has been used with COVID-19 and a decrease in thrombi and mortality has been observed.

In regard to the behavior of APLS in patients with RVO, it should be noted that this disease has special characteristics. It is mainly associated with manifestations of arteriosclerosis and not with onset of deep vein thrombosis or pulmonary embolism; antiplatelet therapy is the treatment of choice for it17. One of our patients presented with pneumonia and three required hospital admission.

COVID-19 has been associated with the onset of artery and vein occlusion, microinfarcts, and multiple organ failure as a result of the hyperinflammatory state and thrombosis generated by the host as a response to SARS-CoV-2 infection. These manifestations are more frequent in severe forms of the disease5. RVO can occur with mild SARS-CoV-2 disease, as in our patient, and it has been recorded in the literature7,8.

The main limitations of this work are the small number of cases reported and the fact that the majority are mild forms of COVID-19.

Conclusions

RVO is a rare manifestation of COVID-19. However, it is advisable to take this entity into account when patients with COVID-19 report ocular symptoms such as a decline in visual acuity. In our prospective cohort of patients with RVO who receive treatment for controlling VRF and thrombophilia, SARS-CoV-2 infection did not seem to worsen RVO or favor the onset of new vascular events.

Funding

No funding of any kind has been received for this work.

Conflicts of interest

The authors declare that they do not have any conflicts of interest in regard to this work.

References
[1]
J.J. Napal, S. Neila, R. Pérez-Montes, I. Sierra, S. Ruiz, J.L. Hernández.
The role of coagulation disorders in patients with retinal vein occlusion.
QJM, 109 (2016), pp. 97-102
[2]
M. Lisa Gracia, A. Córdoba Alonso, J.L. Hernández Hernández, R. Pérez Montes, J.J. Napal Lecumberri.
Factores de riesgo vascular, fibrilación auricular no valvular y obstrucción venosa retiniana.
Rev Clin Esp, 217 (2017), pp. 188-192
[3]
K. Xu, L. Wu, Z. Ma, Y. Liu, F. Quian.
Primary angle closure and primary angle closure glaucoma in retinal vein occlusion.
Acta Ophthalmol, 97 (2019), pp. e364-e372
[4]
W.J. Guan, Z.Y. Ni, Y. Hu, W.H. Liang, C.Q. Ou, J.X. He, et al.
Clinical characteristics of coronavirus disease 2019 in China.
N Engl J Med, 382 (2020), pp. 1708-1720
[5]
C.C. Lai, T.P. Shih, W.C. Ko, H.J. Tang, P.R. Hsueh.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges.
Int J Antimicrob Agents, 55 (2020), pp. 105924
[6]
J.M. Connors, J.H. Levy.
COVID-19 and its implications for thrombosis and anticoagulation.
Blood, 135 (2020), pp. 2033-2040
[7]
J.U. Sheth, R. Narayanan, J. Goyal, V. Goyal.
Retinal vein occlusion in COVID-19: a novel entity.
Indian J Ophthalmol, 68 (2020), pp. 2291-2293
[8]
T. Yahalomi, J. Pikkel, R. Arnon, Y. Pessach.
Central retinal vein occlusion in a young healthy COVID-19 patient: a case report.
Am J Ophthalmol Case Rep, 20 (2020), pp. 100992
[9]
A. Invernizzi, M. Pellegrini, D. Messenio, M. Cereda, P. Olivieri, A.M. Brambilla, et al.
Impending central retinal vein occlusion in a patient with coronavirus disease 2019 (COVID-19).
Ocul Immunol Inflamm, 28 (2020), pp. 1290-1292
[10]
W.H. Gaba, D. Ahmed, R.K. Al Nuaimi, A.A. Al Dhanhani, H. Eatmadi.
Bilateral central retinal vein occlusion in a 40-year-old man with severe coronavirus disease 2019 (COVID-19) pneumonia.
Am J Case Rep, 21 (2020), pp. e927691
[11]
D. Rego Lorca, A. Rouco Fernandez, M. Jimenez Santos, F. Saenz-Frances, B. Burgos-Blasco, J. Donate Lopez.
Bilateral retinal vein occlusion and diabetic retinopathy after COVID-19.
Acta Ophthalmol, (2020),
[12]
Standards of Medical Care in Diabetes-2011. American Diabetes Association. Diabetes care 2011; 34 Supplement 1: S11–S61. https://doi.org/10.2337/dc11-S011.
[13]
S. Miyakis, M.D. Lockshin, T. Atsumi, D.W. Branch, R.L. Brey, R. Cervera, et al.
International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).
J Thromb Haemost, 4 (2006), pp. 295-306
[14]
Situación epidemiológica de la COVID-19 en Cantabria. Web Servicio Cántabro de Salud. [Accessed 15 December 2020]. Available from: https://www.scsalud.es/coronavirus.
[15]
Ministerio de Sanidad del Gobierno de España. Profesionales. Situación COVID-19 en España [Accessed 15 December 2020]. Available from: https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/situacionActual.htm.
[16]
I. Coskun Benlidayi, B. Kurtaran, E. Tirasci, R. Guzel.
Coronavirus disease 2019 (COVID-19) in a patient with ankylosing spondylitis treated with secukinumab: a case-based review.
Rheumatol Int, 40 (2020), pp. 1707-1716
[17]
J.L. Hernández, I. Sanlés, R. Pérez-Montes, V.M. Martínez-Taboada, J.M. Olmos, Z. Salmón, et al.
Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion.
Thromb Res, 190 (2020), pp. 63-68

Please cite this article as: García Palacios JD, Puente Ruiz N, Napal Lecumberri JJ, Hernández Hernández JL. Efectos de la pandemia por SARS-CoV-2 en una cohorte de pacientes con obstrucción venosa retiniana. Rev Clin Esp. 2021;221:587–591.

Copyright © 2021. Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)
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