Tomographic Findings in the Retina of Unvaccinated Patients with COVID Pneumonia: Prospective Longitudinal Study.

There is no definitive evidence on the extent of SARS-CoV-2's effect on the retina. This study aims to determine if the natural history of SARS-CoV-2 infection affects tomographic findings in the retina of patients with COVID-19 pneumonia. This is a prospective cohort study of patients hospitalized with COVID-19 pneumonia. The patients underwent ophthalmological explorations and optical coherence tomography during the acute phase of the infection and at a follow-up 12 weeks later. The primary outcomes were the central retinal thickness and central choroidal thickness, which were compared longitudinally and with non-COVID-19 historical controls. No statistically relevant differences were observed in the longitudinal analysis of the thickness of the central retina (p = 0.056), central choroid (p = 0.99), retinal nerve fiber layer (p = 0.21), or ganglion cell layer (p = 0.32). Patients with acute COVID-19 pneumonia showed significantly greater central retinal thickness than non-COVID controls (p = 0.006). In conclusion, tomographic measures of the retina and choroid are not influenced by the phase of COVID-19 infection and remain stable during 12 weeks. The central retinal thickness may increase in the acute phase of COVID-19 pneumonia, but more epidemiological studies using optical coherence tomography in the early stages of the disease are needed.

Evaluation of vascular and perfusional changes in the retina and choroid of children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is hyperinflammation following coronavirus disease 2019 (COVID-19), which affects many organs. The retina and choroid are affected by COVID-19 through microangiopathy and thrombosis but the literature on MISC-C is limited. METHODS: Thirty children (60 eyes) with MIS-C (the study group, or SG) and 32 age-and gender-matched healthy children (64 eyes) (the control group, or CG) were included in the prospective case-control study. Complete ophthalmological examinations, measurements of the vessel densities of the retinal layers, and flow area of the outer retina and choriocapillaris in both groups were conducted with optical coherence tomography angiography (OCT-A). RESULTS: The mean age of the SG was 11.9 ± 3.9 and that of the CG was 12.5 ± 4.6 years (p = 0.197). In this study we found that the vessel density of the deep layer of the inner retina was decreased significantly and was reduced in the outer retina of flow area in the SG in comparison with the CG (p < 0.05, for all). However, there was no significant difference between the groups regarding other measurements. CONCLUSIONS: In MIS-C patients, vessel densities in the deep layer of the inner retina and in the flow area of the outer retina decreased significantly. This OCTA-A finding suggests that MIS-C is related to endothelial thrombotic condition problems in small branches of the retinal artery. The results of this study support the idea that there is a need for screening of MIS-C patients for the presence of these microangiopathic and perfusional complications.

Retinal microvascular changes in patients recovered from COVID-19 compared to healthy controls: A meta-analysis.

PURPOSE: To investigate changes in retinal microcirculation in patients recovered from COVID-19 infection compared to healthy controls, using optical coherence tomography-angiography. METHODS: Meta-analysis of eligible studies comparing retinal microcirculation between patients recovered from COVID-19 infection and healthy controls up to 7th of September 2022 was performed, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. The following search algorithm was used: (COVID-19 OR coronavirus) AND (retina OR optical coherence tomography OR optical coherence tomography angiography OR vessel density OR foveal avascular zone). Standardized Mean Difference (SMD) with 95% confidence interval (CI) was calculated to compare continuous variables. Revman 5.3 was used for the analysis. RESULTS: 12 studies were included in our analysis. Foveal avascular zone (FAZ) area was larger in patients recovered from COVID-19 infection compared to healthy controls, while there was no statistically significant difference in FAZ perimeter between the two groups. The foveal, parafoveal and whole image vessel density in the superficial capillary plexus showed no significant difference between the two groups. The foveal, parafoveal and whole image vessel density in the deep capillary plexus was statistically lower in patients recovered from COVID-19 compared to healthy controls. CONCLUSION: FAZ area was enlarged and foveal, parafoveal and whole image vessel density in deep capillary plexus were reduced in patients recovered from COVID-19 infection compared to healthy controls, suggesting that COVID-19 infection may induce long-term retinal microvascular changes in patients recovered from the virus infection.

Retinal tissue and microvasculature loss in COVID-19 infection.

This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p < 0.05). Retinal tissue and microvascular loss may be a biomarker of COVID-19 severity. Further monitoring of the retina in COVID-19-recovered patients may help further understand the COVID-19 sequela.

Retinal microvascular impairment in COVID-19 patients: A meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic in an unprecedented time frame. Systemic vascular involvement in COVID-19 has been identified, and SARS-CoV-2 has also been found to cause multiple organ ischemia and posterior ocular segment disease in mammals, raising concerns about the human retinal microvascular involvement in SARS-CoV-2. OBJECTIVE: To objectively assess the presence of retinal microvascular impairment in COVID-19 patients by optical coherence tomography angiography (OCTA), so as to facilitate the clinical system management of COVID-19 patients. METHODS: We searched PubMed, Cochrane Library, EMBASE, Ovid, CBM to collect eligible studies. The main outcomes included the vessel density (VD), area or perimeter of foveal avascular zone (FAZ), central foveal thickness (CFT), subfoveal choroidal thickness (SCT) in our meta-analysis. RESULTS: We eventually included five studies with a total of 401 participants. Our meta-analysis showed that nonacute infectious COVID-19 or post-COVID-19 patients presented significantly lower foveal VD of deep capillary plexus (WMD = -4.22, 95% CI [-8.00, -0.43]) and thinner SCT (WMD = -10.33, 95% CI [-19.08, -1.57]) than healthy controls. The foveal VD and parafoveal VD of superficial capillary plexus, parafoveal VD of deep capillary plexus, CFT, area, and perimeter of FAZ showed no significant differences between the groups. CONCLUSION: The patients of nonacute infectious COVID-19 or post-COVID-19 displayed alterations in the retinal microvasculature and choroidal vessels, including a significantly lower foveal VD in deep capillary plexus and thinner SCT. The impairment may be a medium to long-term process. Close ophthalmic surveillance is necessary for COVID-19 patients or post-COVID-19 patients.

Overview of the retina and imaging in patients with severe acute respiratory syndrome coronavirus 2.

INTRODUCTION: The role of the human eye in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is still under investigation. The pathophysiology of the ocular findings is arduous when dealing with critically ill Covid-19 patients with comorbidities. Multiorgan involvement and the effects of inflammation, infection and systemic treatment on the retina are complex, and comparison of studies is difficult. Most studies in human patients have investigated the anterior segment, whereas few reports deal with the posterior segment of the eye. The present review aims to evaluate the retinal manifestations and imaging features in COVID-19 patients. METHODS: Studies on the retinal manifestations and retinal imaging in COVID-19 patients published through June 2021 were reviewed. We included cross-sectional and case-control studies, case series, case reports and correspondence in the analysis. RESULTS: Flame-shaped hemorrhages, cotton wool spots, augmented diameter and tortuosity of retinal vessels were found on funduscopic examination. Peripapillary, macular retinal nerve fiber layer and ganglion cell layer thickness alterations were reported on spectral domain optical coherence tomography. Reduced vessel density of the superficial and deep retinal capillary plexus on optical coherence tomography angiography was reported. CONCLUSIONS: Retinal complications may arise in COVID-19 patients. Although no consensus on presentation is currently available, retinal funduscopy and imaging has shown neuronal and vascular alterations. Systemic neurological complications and microangiopathy are associated with SARS-COV-2; thus, as the retina has a neuronal and vascular component, funduscopy and retinal imaging on COVID-19 patients can provide further insight to SARS-COV-2 disease and the follow-up of patients.

Retinal vessels modifications in acute and post-COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2 primarily affecting the respiratory system which can damage vessels walls virtually in any body district. Changes affecting retinal vessels are a good marker for systemic vascular alterations. This study investigated retinal vessels during the acute phase of COVID-19 and after patients recovery. Fifty-nine eyes from 32 COVID-19 patients and 80 eyes from 53 unexposed subjects were included. Mean arteries diameter (MAD) and mean veins diameter (MVD) were assessed through semi-automatic analysis on fundus color photos at baseline and 6 months later in patients and subjects unexposed to the virus. At baseline MAD and MVD were significantly higher in COVID-19 patients compared to unexposed subjects (p < 0.0001). Both MAD and MVD significantly decreased in COVID-19 patients at follow-up (from 97.5 ± 10.9 to 92.2 ± 11.4 µm, p < 0.0001 and from 133.1 ± 19.3 to 124.6 ± 16.1 µm, p < 0.0001, respectively). Despite this reduction vessels diameter remained significantly higher in severe COVID-19 patients compared to unexposed subjects. Transient retinal vessels dilation could serve a biomarker for systemic inflammation while long-lasting alterations seen in severe COVID-19 likely reflect irreversible structural damage to the vessels walls and should be further investigated for their possible effects on tissues perfusion and function.

Severe COVID-19 and Retina: Are There Any Retinal Manifestations?

PURPOSE: To investigate whether there are retinal lesions associated with severe COVID-19. METHODS: We studied 232 symptomatic subjects aged 18 - 65 years who had severe COVID-19 and had received treatment. The evaluations included ophthalmological examinations, optical coherence tomography (OCT), imaging modalities with near infrared reflectance (NIR), fundus autofluorescence (FAF), and fundus photography (FP). RESULTS: The mean age of the patients was 49 years, and 67.6% of them were men. There were no findings of microhemorrhage, cotton wool spots (CWS), vitritis, or retinitis in the examination and imaging. CONCLUSIONS: This study indicates that retinal involvement as a complication associated with COVID-19 is questionable, although some reports have demonstrated a relationship that may occur secondary to existing systemic diseases.

COVID-19 Retinal Findings in Patients Admitted to Intensive Care Units and Wards.

The main purpose of this study was to investigate ocular clinical findings in patients with confirmed COVID-19 infection, of various levels of disease severity, who required mechanical ventilation and admission to intensive care units or specialized wards. Longitudinal, observational study conducted from March 2020 to June 2020. Color fundus and red-free photography were performed in both eyes following pupillary dilation. 104 participants were recruited from 2 different centers: 60 (58%) from the Hospital Municipal de Barueri intensive care unit (ICU) and 44 (42%) from specialized wards for patients with COVID-19 at the Hospital São Paulo. 21.9% presented with eye lesions, in 3% these lesions were vision compromising. Our results have shown similar rate of intraocular lesions in patients in both the ward or intensive care unit, regardless of medication use, including anticoagulant drugs.

Outcomes following implementation of a high-volume medical retina virtual clinic utilising a diagnostic hub during COVID-19.

BACKGROUND: To describe the clinical outcomes following implementation of a high-volume medical retina virtual clinic utilising a diagnostic hub. METHODS: Retrospective consecutive case-series of all patients attending the medical retina virtual clinics at Moorfields Eye Hospital (City Road) for 6 weeks from September 21, 2020. RESULTS: In 6 weeks, 1006 patients attended the medical retina virtual clinics, which included an appointment in the diagnostic hub followed by an assessment asynchronously the following working day. The vast majority of patients were follow-up attendances (969, 96.3%) with much fewer new patient attendances (37, 3.7%). The most common diagnoses made overall were diabetic retinopathy (457, 45.4%), age-related macular degeneration (208, 20.7%) and retinal vein occlusion (80, 8.0%). The majority of patient (643, 63.9%) outcomes were follow-up in the medical retina virtual clinics including 313 (31.1%) with OCT-only pathway and 330 (32.8%) with OCT and widefield fundus imaging. Routine follow-up requested after virtual assessment included 320 (31.8%) with a 3-4 month review and 267 (26.5%) with a 6 months assessment. Only 62 patients (6.2%) were asked to return for face-to-face assessment within 2 weeks. CONCLUSIONS: We describe a new high-volume medical retina virtual clinic utilising a diagnostic hub in which more than 1000 patients were seen and assessed asynchronously. Most patients were assessed as suitable for routine follow-up in this virtual pathway and only a small proportion required urgent reviews (within 2 weeks). In the COVID-19 era, this form of high-volume virtual clinic has the potential to review patients efficiently and safely.

Diabetic retinopathy screening in urban primary care setting with a handheld smartphone-based retinal camera.

AIMS: To evaluate diabetic retinopathy (DR) screening with a portable handheld smartphone-based retinal camera and telemedicine in an urban primary healthcare setting and to evaluate the learning curve for image acquisition, performed by healthcare personnel without previous experience in retinal imaging. METHODS: This was a prospective study that enrolled patients with type 2 diabetes mellitus (T2DM) followed at a primary healthcare unit in São Paulo, Brazil. After a brief training in image acquisition, there was further continuous feedback given by a retina specialist during the remote image reading process. Each patient underwent two fundus and one anterior ocular segment images per eye, after mydriasis. Patients were classified according to the need of referral. RESULTS: A total of 627 adult individuals with T2DM underwent retinal evaluation. The population was composed by 63.2% female individuals, age median of 66 years, diabetes duration 10.7 ± 8.2 years and HbA1c 7.7 ± 1.9% (61 + 20.8 mmol/mol). The most prevalent associated comorbidities were arterial hypertension (80.3%) and dyslipidemia (50.2%). Referral decision was possible in 81.2% patients. Most patients had absent or non-referable DR; the main ocular media opacity detected was cataract. After the 7th day of image acquisition, the daily rate of patients whose images allowed clinical decision was maintained above 80%. A higher HbA1c was associated with referable DR. CONCLUSIONS: A low-cost DR screening strategy with a handheld device and telemedicine is feasible and has the potential to increase coverage of DR screening in underserved areas; the possibility of mobile units is relevant for DR screening in the context of COVID-19 pandemic. Daily rate of patients whose examinations allowed clinical decision. X-axis: day of examination; Y-axis: rate (%) of patients whose examinations allowed a clinical decision.

Retinal imaging study diagnoses in COVID-19: a case report.

BACKGROUND: Hyperreflective lesions at the level of ganglion cell (GCL) and inner plexiform retinal layers (IPL) by optical coherence tomography (OCT) and cotton wool spots in the examination of the eye fundus have recently been described as findings in patients with COVID-19 infection. CASE REPORT: We report the case of a 42-year-old healthy Caucasian male anesthetist who had treated COVID-19 patients during the previous 5 weeks and suddenly presented with a temporal relative scotoma in his left eye. Best-corrected visual acuity was 20/20 for the left eye, and no discromatopsy or afferent pupillary defect was present. Visual field test was performed, with no significant findings associated with the focal loss of sensitivity described by the patient. The anterior segment was unremarkable on slit lamp examination in both eyes. Fundus examination of the left eye showed no significant findings. A placoid, hyperreflective band at the level of the GCL and IPL was visible in OCT which spared the outer retina, at the time of diagnosis and 1 month later. An oropharyngeal swab test was performed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA), immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) determination. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) was negative. ELISA testing and a third rapid antibody detection test performed 7 days after the onset of symptoms were positive. CONCLUSIONS: Ocular signs and symptoms in COVID-19 cases are rarely reported, but may be underestimated, especially those that affect the retina and occur in asymptomatic or paucisymptomatic cases. We present a case of COVID-19 diagnosis based on retinal ophthalmic examination.

Retinal capillary involvement in early post-COVID-19 patients: a healthy controlled study.

BACKGROUND: Systemic vascular involvement in COVID-19 has been identified in several patients: not only endothelial derangement and increased permeability are reported to be early hallmarks of organ damage in patients with COVID-19 but are also the most important cause of worsening of clinical conditions in severe cases of SARS-CoV-2 infection. There are several reasons to hypothesize that the eye, and the retina in particular, could be a target of organ damage in SARS-CoV-2 infection. METHODS: This cohort observational study analyzes OCT angiography and structural OCT of 70 post-COVID-19 patients evaluated at 1-month hospital discharge and 22 healthy control subjects. Primary outcomes were macular vessel density (VD) and vessel perfusion (VP); structural OCT features were evaluated as secondary outcomes. In addition, patients and healthy volunteers were evaluated for best corrected visual acuity, slit lamp photograph, and fundus photo image. RESULTS: VD and VP in 3 × 3 and 6 × 6 mm scans for SCP and DCP showed no significant differences between the groups. Similarly, CMT and GCL did not reveal significant differences between post-COVID-19 and healthy patients. Nine patients (12.9%) featured retinal cotton wool spots and 10 patients had vitreous fibrillary degeneration. The prevalence of epiretinal membrane and macular hole was similar in the two groups. One case of extra papillary focal retinal hemorrhage was reported in the post-COVID-19 group. CONCLUSIONS: Macula and perimacular vessel density and perfusion resulted unaltered in mild post-COVID-19 patients at 1-month hospital discharge, suggesting no or minimal retinal vascular involvement by SARS-CoV-2.

Retinal findings in hospitalised patients with severe COVID-19.

AIM: To identify retinal findings using dilated eye examination, which are possibly related to SARS-CoV-2 infection in hospitalised patients with confirmed severe COVID-19. METHODS: In this cross-sectional study, hospitalised patients with confirmed severe COVID-19 in a single referral centre for the treatment of COVID-19, in Santo André, São Paulo Metropolitan Area, Brazil, underwent dilated eye examination of both eyes performed by a retina specialist. Findings were recorded using a portable digital fundus camera. Retinographies were analysed by two retina specialists. Medical records were reviewed for assessment of patient demographics, baseline comorbidities and clinical data. RESULTS: There were a total of 18 patients, nine (50%) male, median IQR age of 62.5 (12) years. Ten of the 18 patients (55.6%; 95% CI 33.7 to 75.4) had abnormalities on dilated eye examination. The main findings were flame-shaped haemorrhages (N=4; 22.2%; 95% CI 9.0 to 45.2) and ischaemic pattern lesions (cotton wool spots and retinal sectorial pallor) (N=4; 22.2%; 95% CI 9.0 to 45.2), with one patient having both cotton wool spots and flame-shaped haemorrhages. CONCLUSION: These findings suggest that patients with severe COVID-19 have acute vascular lesions of the inner retina including flame-shaped haemorrhages and cotton wool spots. Further studies controlling for confounding factors are necessary to properly assess these findings so as to increase the understanding of COVID-19 pathophysiology and to identify new therapies.