Retinal Vascular Changes in Patients After Coronavirus Disease 2019 (COVID-19)

Study Overview
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Brief Summary
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The study examines changes in retinal oximetry in patients after COVID-19 disease. It aims to analyze and quantify possible retinal microvascular abnormalities that may result from possible post-inflammatory damage to the endothelium of the vessels associated with COVID-19 disease. Retinal vascular involvement may indicate similar changes in the vascular system in other organs.

Detailed Description
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The retinal blood vessels are the only blood vessels in the body that can be observed directly. Patients with COVID-19 pneumonia have been shown to have reduced macular vessel density in the foveal region. As a result, some layers of the retina atrophy, reducing oxygen consumption by the retina. Based on this, it is expected that patients after COVID-19 pneumonia, or after a more severe course of the disease, will have normal arterial retinal oxygen saturation but higher venous retinal oxygen saturation and lower arterio-venous difference than patients after mild disease.

Official Title
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Retinal Vascular Changes in Patients After Coronavirus Disease 2019 (COVID-19) Based on Retinal Oximetry

Conditions
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COVID-19

Intervention / Treatment
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* Diagnostic Test: Central visual acuity
* Diagnostic Test: Intraocular pressure measurement
* Diagnostic Test: Slit lamp examination
* Diagnostic Test: Retinal oximetry
* Diagnostic Test: Optical coherence tomography and angiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 years history of laboratory-confirmed SARS-CoV2-infection transparent ocular media allowing for fundus photography signed informed consent Exclusion Criteria: known eye disease that has been shown to affect retinal oxygen saturation (diabetic retinopathy, vascular occlusions, use of antiglaucoma drugs) any other serious eye disease (advanced or decompensated glaucoma, retinitis pigmentosa, age-related macular degeneration, ocular tumors) reduced transparency of the ocular media limiting the visualization of the ocular background and preventing a good quality image from being taken (severe dry eye syndrome, corneal scarring, cataract, significant vitreous haze, vitreous hemorrhage) significant refractive error not allowing for sharpening of imaging examinations previous intraocular surgery except cataract surgery if performed more than 3 months before the examination previous intravitreal application of anti-vascular endothelial growth factor therapy or laser photocoagulation of the retina previous severe eye injury acute eye infection known systemic disease affecting retinal oxygen saturation or causing changes in the ocular background (chronic obstructive pulmonary disease, multiple myeloma, malignant hypertension, hyperglobulinemia) pregnancy, breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mild disease<br>asymptomatic or paucisymptomatic patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV2-infection) who received outpatient care | Diagnostic Test: Central visual acuity<br>* Measurement of central visual acuity using ETDRS (Early Treatment Diabetic Retinopathy Study) optotypes or Snellen optotype chart.<br>Diagnostic Test: Intraocular pressure measurement<br>* Measurement of intraocular pressure using non-contact Canon TX-20P tonometer.<br>Diagnostic Test: Slit lamp examination<br>* Slit lamp examination of the anterior and posterior segment of the eye after pharmacological dilation of the pupil using application of short-time mydriatics (1% tropicamide and 10% phenylephrine).<br>Diagnostic Test: Retinal oximetry<br>* Performing of retinal oximetry with an Oxymap T1 instrument (Oxymap ehf.) paired with a Topcon TRC-50DX retinal camera.<br>Diagnostic Test: Optical coherence tomography and angiography<br>* Performing of optical coherence tomography and angiography with the Spectralis Optical Coherence Tomography Plus (Heidelberg Engineering).<br>|
| moderate disease<br>patients with laboratory-confirmed SARS-CoV2-infection and radiology-confirmed pneumonia who did not require extracorporeal membrane oxygenation | Diagnostic Test: Central visual acuity<br>* Measurement of central visual acuity using ETDRS (Early Treatment Diabetic Retinopathy Study) optotypes or Snellen optotype chart.<br>Diagnostic Test: Intraocular pressure measurement<br>* Measurement of intraocular pressure using non-contact Canon TX-20P tonometer.<br>Diagnostic Test: Slit lamp examination<br>* Slit lamp examination of the anterior and posterior segment of the eye after pharmacological dilation of the pupil using application of short-time mydriatics (1% tropicamide and 10% phenylephrine).<br>Diagnostic Test: Retinal oximetry<br>* Performing of retinal oximetry with an Oxymap T1 instrument (Oxymap ehf.) paired with a Topcon TRC-50DX retinal camera.<br>Diagnostic Test: Optical coherence tomography and angiography<br>* Performing of optical coherence tomography and angiography with the Spectralis Optical Coherence Tomography Plus (Heidelberg Engineering).<br>|
| severe disease<br>patients with laboratory-confirmed SARS-CoV2-infection and acute respiratory distress syndrome who required extracorporeal membrane oxygenation | Diagnostic Test: Central visual acuity<br>* Measurement of central visual acuity using ETDRS (Early Treatment Diabetic Retinopathy Study) optotypes or Snellen optotype chart.<br>Diagnostic Test: Intraocular pressure measurement<br>* Measurement of intraocular pressure using non-contact Canon TX-20P tonometer.<br>Diagnostic Test: Slit lamp examination<br>* Slit lamp examination of the anterior and posterior segment of the eye after pharmacological dilation of the pupil using application of short-time mydriatics (1% tropicamide and 10% phenylephrine).<br>Diagnostic Test: Retinal oximetry<br>* Performing of retinal oximetry with an Oxymap T1 instrument (Oxymap ehf.) paired with a Topcon TRC-50DX retinal camera.<br>Diagnostic Test: Optical coherence tomography and angiography<br>* Performing of optical coherence tomography and angiography with the Spectralis Optical Coherence Tomography Plus (Heidelberg Engineering).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful performing of retinal oximetry images in 90% of enrolled patients. | 90% of captured fundus images of retinal oximetry are useful for subsequent analysis. | 3 months | 
| Successful analysis of retinal oxygen saturation in 90% of enrolled patients. | The parameters analyzed by retinal oximetry are arterial retinal oxygen saturation (%), venous retinal oxygen saturation (%), arterio-venous difference (%), arteriolar and venular diameter (µm). | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful performing of optical coherence tomography and angiography in 90% of enrolled patients. | 90% of captured images of optical coherence tomography and angiography are useful for subsequent analysis. | 3 months | 
| Successful analysis of optical coherence tomography in 90% of enrolled patients. | The parameters analyzed by optical coherence tomography are central retinal thickness (µm), ganglion cell layer thickness (µm), retinal nerve fiber layer thickness (µm), choroid thickness (µm) in the macular region and optic nerve head retinal nerve fiber layer thickness (µm). | 3 months | 
| Successful analysis of optical coherence tomography angiography in 90% of enrolled patients. | The parameter analyzed by optical coherence tomography angiography is the size of foveal avascular zone (µm2). | 3 months |