COVID-19 informace

Authors:K. Thiran Jayasundera, MD, MS; Rebhi O. Abuzaitoun, MD; David C. Musch, PhD, MPH

JAMA Ophthalmology Published online April 14, 2022

Modjtahedi and colleagues’ access to the large Kaiser Permanente

database has revealed an interesting and potentially

causal association between COVID-19 infection and the subsequent

incidence of retinal vascular occlusions.1COVID-19can

cause a wide array of systemiccomplications (arrhythmias,

secondary infections,coagulopathies)2 and ocular manifestations (cranial nerve

palsies, conjunctivitis, retinal microvascular changes).3 Vascular

damage underlies the damage caused by COVID-19 to

multiple organs via 2 main mechanisms: disseminated intravascular

coagulation–like reaction leading to hypercoagulability and direct viral infection of the endothelial cells leading to a vasculitis-like picture.4 Furthermore, patients with

COVID-19 are predisposed to embolism formation due to intravascular

coagulation and hypoxia.5 The combination of COVID-19’s vascular damage and higher embolism formation tendencies can hypothetically increase the risk of retinal vascular

occlusion. Previous publications reporting retinal vascular occlusion (artery6 or vein7) secondary to COVID-19 infection have been case reports, which lack a study design (eg,

case-control or cohort studies) wherein hypothesis testing is used to evaluate this association in a group of individuals. In order to test for a causal association between exposure (COVID-19) and disease (retinal vascular occlusion), the following

9 aspects (known as the Bradford Hill criteria) should be taken into account: strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence,

experiment, and analogy. In the study by Modjtahedi et al,1 the retrospective cohort

study design does assess temporality, as all patients who were diagnosedwithCOVID-19were followed up for 6months todetect the incidence rate of retinal vascular occlusion postinfection. Furthermore, there is support from case studies reporting

occurrence of retinal vascular occlusion after infection with COVID-19.6,7

The strength of association was assessed by the incidence rate ratio, which measures the increment of retinal vascular occlusion incidence from pre– to post–COVID-19 infection. None of the previous publications focusing onretinal vascular occlusion secondary to COVID-19 involved a group of individuals;therefore, none had a measure for strength of association.

Biological plausibility exists between the cause and effect. COVID-19 leads to vascular damage through disseminated intravascular coagulation and a vasculitis-like reaction.

COVID-19 also leads to a higher tendency of thrombus formation through intravascular coagulation and hypoxia.

Vascular damage and thrombus formation are risk factors that

can lead to retinal vascular occlusion.

There is consistency inreporting of this association as findings

of this retrospective cohort study are consistent with

previous published case reports of retinal vascular occlusion

attributed to COVID-19.

Experimental evidence is lacking and would require the

study of COVID-19 infection in large animal models.

The dose-response association between exposure and

disease has not been thoroughly examined. One would expect

that a severe COVID-19 infectionwould lead to more vascular

occlusions; however, thismay be negated by the anticoagulation

regimens initiated in hospitalized patients with severe COVID-19.

In conclusion, the retrospective cohort studybyModjtahedi

et al further strengthens the association betweenCOVID-19and

retinalvascularocclusion.However,thestrengthandconsistency

of this association would be enhanced by further evaluation

includingstudiesthataccessotherlargedatabasesnowavailable,

to provide a robust basis for causality and help determine recommended

strategies for prevention and surveillance.