COVID-19 presenting as a non-arteritic anterior ischemic optic neuropathy.

We present a case of a 61-year-old woman with an atypical non-arteritic anterior ischemic optic neuropathy (NA-AION) as a unique manifestation of COVID-19. Furthermore, the patient worsened after Pfizer-BioNTech COVID-19 vaccine administration. Our findings suggest that NA-AION could result from microangiopathic/thrombotic events that may occur during SARS-CoV-2 infection and/or vaccination against COVID-19. This report sheds light on possible ophthalmologic complications of COVID-19.

Impaired Endothelial Function in Convalescent Phase of COVID-19: A 3 Month Follow Up Observational Prospective Study.

BACKGROUND: Endothelial dysfunction has a role in acute COVID-19, contributing to systemic inflammatory syndrome, acute respiratory distress syndrome, and vascular events. Evidence regarding COVID-19 middle- and long-term consequences on endothelium are still lacking. Our study aimed to evaluate if COVID-19 severity could significantly affect the endothelial function after three months from the acute phase. METHODS: We assessed endothelial function in outpatients with previous COVID-19 three months after negative SARS-CoV-2 molecular test by measuring flow-mediated dilation (FMD) in patients categorized according to a four-variable COVID-19 severity scale ("home care"; "hospital, no oxygen"; "hospital, oxygen"; "hospital requiring high-flow nasal canula, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation"). FMD difference among COVID-19 severity categories was assessed with analysis of variance; we further clarified the relationship between FMD and previous COVID-19 severity with multivariate logistic models. RESULTS: Among 658 consecutive COVID-19 subjects, we observed a significant linear trend of FMD reduction with the increase of the COVID-19 category (p < 0.0001). The presence of endothelial dysfunction was more frequent among hospitalized patients (78.3%) with respect to home-care patients (21.7%; p < 0.0001). COVID-19 severity was associated with increased endothelial dysfunction risk (OR: 1.354; 95% CI: 1.06-1.71; p = 0.011) at multivariate binary logistic analysis. FMD showed a significant direct correlation with PaO2 (p = 0.004), P/F ratio (p = 0.004), FEV1 (p = 0.008), and 6MWT (p = 0.0001). CONCLUSIONS: Hospitalized COVID-19 subjects showed an impaired endothelial function three months after the acute phase that correlated with pulmonary function impairment. Further studies are needed to evaluate if these subjects are at higher risk of developing pulmonary disease or future cardiovascular events.

Radial Peripapillary Capillary Plexus Perfusion and Endothelial Dysfunction in Early Post-SARS-CoV-2 Infection.

BACKGROUND: Endothelial cells damage and thromboinflammation are considered key elements in the generation of organ impairment in patients with COVID-19 disease. The endothelial function is evaluated by measuring flow-mediated dilation (FMD). We aimed to analyze the association between FMD impairment and retinal vascular parameters in early post-COVID-19 patients. 00118-00199Tomography (OCT), OCT Angiography (OCTA) and slit lamp examination were performed. FMD ≤ 7% was considered as pathological. Our primary outcome was to assess potential differences in the radial peripapillary capillary plexus flow index (RPCP-FI) and RPCP density (RPCP-D) values between post-COVID-19 patients with and without FMD impairment. The associations of other retinal vascular parameters with FMD impairment were assessed as secondary endpoints. RESULTS: FMD impairment was detected in 31 patients (37.8%). RPCP-FI (p = 0.047), age (p = 0.048) and prevalence of diabetes (p = 0.046) significantly differed in patients with FMD ≤ 7% in regression analysis. RPCP-FI was linearly correlated with FMD values (R = 0.244, p =0.027). SCT was found to be lower in patients with impaired FMD (p = 0.004), although this difference was only a trend in binary logistic regression output (p = 0.07). CONCLUSIONS: Early post-COVID-19 patients showed a higher prevalence of FMD impairment compared to the general population. Age, diabetes and RPCP-FI were independently correlated with the presence of endothelial impairment in the early post-infective period.

Impaired Endothelial Function in Convalescent Phase of COVID-19: A 3 Month Follow Up Observational Prospective Study

Background: Endothelial dysfunction has a role in acute COVID-19, contributing to systemic inflammatory syndrome, acute respiratory distress syndrome, and vascular events. Evidence regarding COVID-19 middle- and long-term consequences on endothelium are still lacking. Our study aimed to evaluate if COVID-19 severity could significantly affect the endothelial function after three months from the acute phase. Methods: We assessed endothelial function in outpatients with previous COVID-19 three months after negative SARS-CoV-2 molecular test by measuring flow-mediated dilation (FMD) in patients categorized according to a four-variable COVID-19 severity scale ('home care';;'hospital, no oxygen';;'hospital, oxygen';;'hospital requiring high-flow nasal canula, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation';). FMD difference among COVID-19 severity categories was assessed with analysis of variance;we further clarified the relationship between FMD and previous COVID-19 severity with multivariate logistic models. Results: Among 658 consecutive COVID-19 subjects, we observed a significant linear trend of FMD reduction with the increase of the COVID-19 category (p < 0.0001). The presence of endothelial dysfunction was more frequent among hospitalized patients (78.3%) with respect to home-care patients (21.7%;p < 0.0001). COVID-19 severity was associated with increased endothelial dysfunction risk (OR: 1.354;95% CI: 1.06–1.71;p = 0.011) at multivariate binary logistic analysis. FMD showed a significant direct correlation with PaO2 (p = 0.004), P/F ratio (p = 0.004), FEV1 (p = 0.008), and 6MWT (p = 0.0001). Conclusions: Hospitalized COVID-19 subjects showed an impaired endothelial function three months after the acute phase that correlated with pulmonary function impairment. Further studies are needed to evaluate if these subjects are at higher risk of developing pulmonary disease or future cardiovascular events.

Retinal vascular impairment matched to the pulmonary damage in early post-COVID 19 patients.

BACKGROUND: Endothelium damage is a crucial element in the pathogenesis of SARS-Cov-2 infection. Most casualties in critical COVID-19 cases are due to ARDS, diffuse coagulopathy and cytokine storm. ARDS itself is a consequence of pulmonary endothelial cells damage. Damage to retinal capillary microcirculation in post-infective period has been investigated through Optical Coherence Tomography Angiography (OCTA). The aim of the present study is to find a correlation between signs of retinal vascular damage and pulmonary impairment. METHODS: Patients admitted to hospital and subsequently recovered from COVID-19 infection were summoned 1 month later to undergo coherence tomography (CT) scan and OCTA examination. RESULTS: The study population included 87 COVID-19 patients with a mean age of 54.28 ± 14.44 years. Oxygen therapy, non-invasive and invasive mechanical ventilation were necessary in 33, 11 and 4 patients respectively to provide respiratory support during the acute course of the disease. Pulmonary involvement interested 54 patients (62.1%). Peripheral (27.6%) or diffuse (29.9%) involvement and ground glass (GG) opacities (47.1%) represented the prevalent radiological finding. A reduced RCPI FI was independently correlated with the presence of reticulation pattern in CT scan (p = .019). Also, RNFL and GCC were thinner in patients who displayed reticulation pattern (respectively p = .025 and p = .015). CONCLUSIONS: A reduction in RPCP-FI and RNFL and GCC thickness were independently correlated to the presence of CT reticulation pattern. This association can reflect cytokine induced remodeling in both organs as a consequence of systemic endothelial damage and inflammation.

Impact of the COVID-19 pandemic on ophthalmologic outpatient care: experience from an Italian Tertiary Medical Center.

PURPOSE: To evaluate the impact the COVID-19-related national lockdown has had on Ophthalmologic Outpatient Care in an Italian Tertiary Medical Centre. METHODS: We reviewed all the performances that were carried out as outpatient services at our department between 1 January 2020 and 30 November 2020. We compared data among four different periods: from 1 January 2020 to 17 March 2020 ("Pre-Lockdown"); from 18 March 2020 to 17 May 2020 (Lockdown); from 18 May 2020 to 2 November 2020 (Post-Lockdown) and from 3 November 2020 to 30 November 2020 (Regional Lockdown). RESULTS: The overall number of performed routine outpatient visits per day (ROVs) was 11,871 (Mean ± SD = 35.76 ± 17.81), whereas booked appointments (BAs) were 21272 (Mean ± SD = 63.86 ± 9.27), meaning a decline in the number of ROVs by 44.01%. (Mean ± SD = 28.10 ± 12.11, p<.001). Post-Lockdown and Regional Lockdown clinical activities, dropped respectively by 31 and 25.14% (38.87 ± 3.88 vs. 56.34 ± 11.06, p<.001 and 6.04 ± 4.51 vs. 56.34 ± 11.06 p<.001). The number of BAs per day decreased during the pandemic, going from a mean of 77.81 ± 2.57 booked appointments per day before the lockdown, to a mean of 53.14 ± 4.94, 61.80 ± 4.62 and 72.07 ± 1.09 appointments per day respectively during the lockdown, the post-lockdown and the regional lockdown periods. CONCLUSIONS: During the various lockdown periods, at our institution the volume of outpatient ophthalmological visits drastically dropped. This testifies the dramatic impact the COVID-19 pandemic has had on the supply of ophthalmic care.

COVID-19 Ocular Prophylaxis: The Potential Role of Ozonated-Oils in Liposome Eyedrop Gel.

Purpose: To assess whether ozonated-oil in liposome eyedrop gel (OED) could be used to prevent the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in an in vitro infection model. Methods: First, we tested the efficacy of OED on in vitro cell regeneration and dry eye resolution in human corneal epithelial cells (hCE-2). Second, we assessed the in vitro anti-SARS-CoV-2 infection efficacy of OED using Vero E6 cells. Tissues were examined to assess different parameters: morphology, histology, and mRNA expression at 24 hours after treatment. Results: OED could restore 50% of the scratch in the monolayer of hCE-2 cells in vitro compared with the 25% obtained with phosphate-buffered saline solution (PBS). At 24 hours after treatment with OED, the number of microvilli and the mucin network were restored, as observed using scanning electron microscopy. In Vero E6 cells infected with a primary SARS-CoV-2 strain and treated with OED two times/day, viral replication was found to be inhibited, with a 70-fold reduction observed at 72 hours after infection compared with that under the untreated and PBS-treated conditions. Conclusions: SARS-CoV-2 transmission through the ocular surface should not be ignored. Although the prevalence of coronavirus disease 2019 conjunctivitis infection is low, the need for a barrier to prevent possible viral infection is warranted. OED treatment may prevent the risk of SARS-CoV-2 infection after 72 hours of twice-daily applications. Translational Relevance: Dry eye condition might be a risk factor for SARS-CoV-2 infection and OED treatment may have a preventive role.

Ocular Surface Impairment After Coronavirus Disease 2019: A Cohort Study.

PURPOSE: This is a cohort study to evaluate the presence of objective signs and subjective symptoms of dry eye disease in postcoronavirus disease 2019 (COVID-19) patients compared with the control. METHODS: Prospective, observational, single-ctenter, cohort study. Sixty-four post-COVID-19 patients and 50 control were recruited. All participants underwent a complete ophthalmological examination including Ocular Surface Disease Index Questionnaire (OSDI), best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, Schirmer test type 1, tear break-up time test (tBUT), evaluation of conjunctival hyperemia, corneal staining, and tear film osmolarity test. RESULTS: The OSDI score was higher in the post-COVID-19 group in the quantitative and qualitative analysis (P < 0.001 and P =0.012, respectively). The mean tBUT in post-COVID-19 patients was 6.95 ± 4.07 seconds compared with a mean tBUT of 10.12 ± 3.90 seconds in the control group. The post-COVID-19 group showed a higher number of patients with a simultaneous impairment of the OSDI score and tBUT (P = 0.019). The Schirmer test results were strikingly significant both in the quantitative analysis and qualitative analysis (P <0.001 and P = 0.0014, respectively). Both quantitative analysis and qualitative analysis revealed a significant difference in tear osmolarity in the 2 groups. CONCLUSIONS: Comparing the ocular surface assessment of post-COVID-19 patients with heathy control, a statistically significant increase of dry eye disease has emerged both in subjective and objective evaluations. Our clinical results support the findings that suggested a susceptibility of the ocular surface to the virus, and it underlines the importance of the ocular surface assessment in post-COVID-19 patients for a correct diagnosis and therapy.

Focal superior quadrant haemorrhages in post COVID-19 patient: A target for personalized medicine.

PURPOSE: To report a case of multiple superior quadrant intraretinal haemorrhages in post-COVID-19 patient. CASE DESCRIPTION: A 58-year-old male with a history of coronary artery disease and hypertension, presented with multiple superior quadrant intraretinal haemorrhages in the superonasal quadrant of the left eye 1 month after hospitalization for COVID-19. The right eye was normal. During his 10-day stay, he was treated with hydroxychloroquine, lopinavir + ritonavir, ceftriaxone, and his pre-existing antiplatelet therapy. During hospitalization, a complete medical work up showed an anomalous increase in D-dimer. He did not require intensive care support. CONCLUSIONS: In this report, we focused on the origin of retinal bleeding in a post COVID-19 patient, likely due to a focal occlusion of a vessel. Considering the nature of SARS-CoV-2 infection, we hypothesize that retinal haemorrhages were caused by a combination of factors including the patient's antiplatelet therapy and the thrombotic microvascular injury caused by the virus.

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.

Evidence-based of conjunctival COVID-19 positivity: An Italian experience: Gemelli Against COVID Group.

BACKGROUND: The possible transmission of severe acute respiratory coronavirus 2 (SARS-CoV-2) by tears and conjunctiva is still debated. METHODS: Main outcome was to investigate the agreement between nasopharyngeal swab (NPs) and conjunctival swabs (Cs) in patients with SARS-CoV-2 infection. We divided patients into four groups: (1) NPs and Cs both negative (C-NF-), (2) NPs positive and Cs negative (NFs+Cs-), (3) NPs negative and Cs positive (NFs-Cs+), and (4) NPs and Cs both positive (NFs-Cs+). The secondary outcomes were to correlate Cs results with systemic clinical parameters such as: oxygen saturation (SpO2), dyspnea degree (DP), radiologic pulmonary impairment based on chest radiography (XR) or computed tomography (CT), blood chemistry as D-Dimer (D-Dimer), fibrinogen, ferritin, lactate dehydrogenase (LDH), and C-reactive protein (C-RP). RESULTS: A total of 100 conjunctival swabs in 50 patients with SARS-CoV-2 have been enrolled in this interventional clinical trials. Ocular signs (conjunctivitis) were present in five patients (10%). NPs and Cs highlighted a poor level of agreement (0.025; p = 0.404). Median SpO2 levels are the highest in the NF-C- group (98%) and the lowest (90%) in the group NF+C+ (p = 0.001). Pulmonary impairment was statistically significantly different between NFs and Cs groups (p = 0.019). Pulmonary impairment score increased from NFs-Cs- group (3.8 ± 3.9), to NFs+Cs+ group (6.7 ± 4.1). Intensive care unit patients showed higher COVID-19 Cs positivity in conjunctiva (12.5%) against hospitalized ones (5.8%). CONCLUSIONS: In patients hospitalized for SARS-CoV-2 the virus can be detected in conjunctival swab. Intensive care unit patients may reveal a higher COVID-19 presence in the conjunctiva. The most severe pulmonary impairment can be observed in NFs and Cs positivity. TRIAL REGISTRATION: Clinicaltrials.gov registration. ETHICAL COMMITTEE AUTHORIZATION: ID number: 0013008/20.

Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients.

The ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2's) to cause multi-organ ischemia and coronavirus-induced posterior segment eye diseases in mammals gave concern about potential sight-threatening ischemia in post coronavirus disease 2019 patients. The radial peripapillary capillary plexus (RPCP) is a sensitive target due to the important role in the vascular supply of the peripapillary retinal nerve fiber layer (RNFL). Eighty patients one month after SARS-CoV-2 infection and 30 healthy patients were selected to undergo structural OCT (optical coherence tomography) and OCTA (optical coherence tomography angiography) exams. Primary outcome was a difference in RPCP perfusion density (RPCP-PD) and RPCP flow index (RPCP-FI). No significant difference was observed in age, sex, intraocular pressure (IOP) and prevalence of myopia. RPCP-PD was lower in post SARS-CoV-2 patients compared to controls. Within the post-COVID-19 group, patients with systemic arterial hypertension had lower RPCP-FI and age was inversely correlated to both RPCP-FI and RPCP-PD. Patients treated with lopinavir + ritonavir or antiplatelet therapy during admission had lower RPCP-FI and RPCP-PD. RNFL average thickness was linearly correlated to RPCP-FI and RPCP-PD within post-COVID-19 group. Future studies will be needed to address the hypothesis of a microvascular retinal impairment in individuals who recovered from SARS-CoV-2 infection.

Possible Retinal Impairment Secondary to Ritonavir Use in SARS-CoV-2 Patients: A Narrative Systematic Review.

Some reports described a possible ritonavir-related retinal toxicity. The objective of this research was to review and analyze previous studies conducted on ritonavir administration and retinal impairment in a narrative synthesis. PubMed was used to perform a systematic review of ritonavir effects and retinal damage. All studies up to December 2019 were considered. Seven single cases and one case series, reporting a total of 10 patients affected by retinal changes secondary to long-term ritonavir treatment, were included in the review. Variable degrees of outer retina and retinal pigment epithelium changes were detected in most of the patients, with two patients showing macular telangiectasia, four patients presenting intraretinal crystal deposits, two patients disclosing a bull's eye maculopathy, and two patients revealing midperipheral bone spicule-like pigment changes. In the present study, we hypothesized that the use of ritonavir in life-saving treatments of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia might expose these patients to the risk of developing a retinotoxicity. We aimed to alert ophthalmologists on the importance of recognizing ritonavir-induced retinal impairment in SARS-CoV-2 patients. These findings are the target for personalized medicine.