Trial Report Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome, 2023, Noor et al.

SNT Gatchaman · Nov 25, 2023

Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome, 2023, Noor et al.

Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome
Noor, Maha; McGrath, Orlaith; Drira, Ines; Aslam, Tariq

Several optical coherence tomography angiography (OCT-A) studies have demonstrated retinal microvascular changes in patients post-SARS-CoV-2 infection, reflecting retinal-systemic microvasculature homology. Post-COVID-19 syndrome (PCS) entails persistent symptoms following SARS-CoV-2 infection.

In this study, we investigated the retinal microvasculature in PCS patients using OCT-angiography and analysed the macular retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness via spectral domain-OCT (SD-OCT). Conducted at the Manchester Royal Eye Hospital, UK, this cross-sectional study compared 40 PCS participants with 40 healthy controls, who underwent ophthalmic assessments, SD-OCT, and OCT-A imaging. OCT-A images from the superficial capillary plexus (SCP) were analysed using an in-house specialised software, OCT-A vascular image analysis (OCTAVIA), measuring the mean large vessel and capillary intensity, vessel density, ischaemia areas, and foveal avascular zone (FAZ) area and circularity. RNFL and GCL thickness was measured using the OCT machine’s software. Retinal evaluations occurred at an average of 15.2 ± 6.9 months post SARS-CoV-2 infection in PCS participants.

Our findings revealed no significant differences between the PCS and control groups in the OCT-A parameters or RNFL and GCL thicknesses, indicating that no long-term damage ensued in the vascular bed or retinal layers within our cohort, providing a degree of reassurance for PCS patients.

Link | PDF (Journal of Imaging)

Hutan · Nov 25, 2023

Post COVID-19 syndrome refers to the persistence of certain clinical symptoms more than 12 weeks after the initial COVID-19 infection, which cannot be explained by an alternative diagnosis [4]. Persistence of symptoms 4 or more weeks after the infection may be referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) [5] or ‘Long COVID’. Symptoms of PCS may include but are not limited to fatigue, dyspnoea, cough, autonomic symptoms (chest pain, palpitations, tachycardia), neurocognitive impairment i.e., ‘brain fog’, arthralgia, myalgia, headaches, anosmia, ageusia, gastrointestinal disturbances, sleep disturbances, hair loss, and psychiatric disorders such as depression and anxiety [5].
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They don't tell us how the PCS people were diagnosed - but they were diagnosed by a respiratory team. I wonder if that skewed the selection to people with lung damage rather than ME/CFS-like disease?

Patients were recruited into two distinct groups for this comparative study. The first group comprised of patients over 18 years of age with an established clinical diagnosis of post-COVID-19 syndrome by the respiratory team at Manchester Royal Infirmary, UK. All included subjects either had a reverse transcription-polymerase chain reaction (RT PCR)—confirmed diagnosis of COVID-19 at an earlier stage or a clinical diagnosis of COVID-19 (as testing was not readily available in the early stages of the pandemic in the UK). Patients recruited within the post-COVID-19 syndrome cohort may have an initial mild, moderate, or severe initial illness with or without requirement for hospitalisation or outpatient treatment, allowing us to examine the retinal microvasculature in a wider range of PCS participants.
The second group, the controls, included patients over 18 years of age who did not have a recent history of COVID-19 infection or a diagnosis of post-COVID-19 syndrome. For both groups, we excluded patients with a history of diabetes, [a long list of eye pathologies]
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The eye can be considered as a window into the body’s microvascular system. Optical coherence tomography angiography (OCT-A) offers a non-invasive opportunity to analyse the retinal circulation in vivo, providing insight into the subject’s systemic microvasculature by inference [61]. Several studies have investigated the retinal vasculature of patients infected with COVID-19 using OCT-A to date. A key finding of note is reduction in the macular vessel density from as early as 2 weeks following the infection up to 8 months afterward [62,63,64,65,66,67,68,69,70,71,72,73,74,75].
Considering the overwhelming amount of literature reporting an alteration in the retinal microvasculature in patients with a history of COVID-19 illness, it is pertinent to investigate whether these effects last long term, especially in patients with ongoing symptoms of post-COVID-19-syndrome. Furthermore, there is currently a paucity of literature examining the retinal vasculature of patients with PCS.
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The field of investigation was centred on the foveal region. Scans had a 10-layer automated segmentation and a refresh rate of 70,000 A-scans/s. The depth of field of view was set to 10 × 10 mm and 4 × 4 mm with an axial sampling density of 464 × 464 px, with the number of repetitions set at two. For the purposes of this study, only the retinal superficial capillary plexus (SPC), which provided the most consistently high-quality images, was examined.
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Is the retinal superficial capillary plexus only enough? I think we have seen a couple of studies of retinal capillaries in Long covid or ME/CFS. How does the selection of what is looked at compare with the other studies?

Hutan · Nov 25, 2023

Notably, we were aware that many PCS participants suffered with dry eyes, fatigue, and dyspnoea, and we opted to include the highest quality imaged eye only for each patient in this study protocol with standard statistical techniques to optimise overall image analysis validity. Lubricants were offered to all patients to mitigate effects of any dry eye disease. Pharmacological mydriasis was attained (tropicamide 1%) in cases where the quality of imaging was affected by lack of pupillary dilatation.
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It sounds as though many of the participants did have fatigue (30/40).

The most prevalent symptoms of post-COVID-19 syndrome identified during clinical history taking were fatigue (30/40), dyspnoea (23/40) of which 4/23 reported exertional dyspnoea, cognitive dysfunction termed “brain fog” (16/40), and palpitations (15/40). Four patients had been diagnosed with paroxysmal orthostatic tachycardia syndrome (POTS). Interestingly, 3/40 patients reported intermittent visual disturbance and 11/40 expressed presence of dry eyes.
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Table 3 is an interesting table of symptoms in the PCS cohort. Only one of the 40 had anxiety and only 2 out of the 40 had depression. "Paroxysmal orthostatic tachycardia syndrome (POTS)" . 16/40 reported cognitive dysfunction.

It does sound as though retinal vasculature is different in different ages and between males and females. But this paper reports that the cohorts were age and gender matched.

Hutan · Nov 25, 2023

Post-COVID-19 syndrome has been linked to a persistent impairment of the systemic microvasculature. This study explored the retinal microvasculature network as a potential window into the pathophysiology of post-COVID-19, considering the known homology of the retinal vascular bed with systemic diseases.
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Our study shows that there were no significant differences found in any of the comprehensive measures used between our populations of people with and without this syndrome.
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We opted to analyse OCT-A images of the superficial retinal plexus, noting the clinical importance of this region and improved quality of imaging compared to intermediate or deep plexi as well as its predominance as a focus of analysis in other publications. However, Schlick et al. recently explored the retinal microvasculature of patients with post-COVID-19 syndrome using OCT-Angiography and found significant changes in the intermediate capillary plexus (ICP), as compared to the controls [89]. Future studies may benefit from attention to improved imaging of intermediate and deeper plexi to assess if this effect is seen longer term.
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This seems like a well-conducted and careful study. But it does seem as though they may have looked where it was easy to look, rather than where a difference might be found.

Their conclusion seems a bit premature:

In this study, we have demonstrated that there were no statistically significant differences in the retinal microvasculature of patients with post-COVID-19 syndrome compared to healthy cohorts. Furthermore, no significant structural differences were observed in the macular retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) of the study participants. The findings of this study indicate that despite an extensive investigation in patients with post-COVID-19 syndrome, there were no long-term structural signs of damage after detailed analysis of this accessible microvasculature bed that is known to have homology with systemic vasculature. This may serve as some positive reassurance for patients experiencing ongoing symptoms of PCS.
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SNT Gatchaman · Nov 25, 2023

Hutan said: ↑

I think we have seen a couple of studies of retinal capillaries in Long covid or ME/CFS. How does the selection of what is looked at compare with the other studies?
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I haven't had a chance to look back but I've just done a search to better tag some existing papers for optical coherence tomography and retina.

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Trial Report Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome, 2023, Noor et al.

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Trial Report Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome, 2023, Noor et al.

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