Detección de anticuerpos anti-SARS-CoV-2 en lágrimas: inmunidad de la superficie ocular frente a COVID-19 Detection of anti-SARS-CoV-2 antibodies in tears: ocular surface immunity to COVID-19

Objetivos: Evaluar la presencia de anticuerpos IgA e IgG específicos del SARS-CoV-2 en lágrima de sujetos no vacunados y vacunados contra la COVID-19 con antecedentes de infección SARS-CoV-2. Correlacionar los resultados en lágrima con los de saliva y sangre, datos clínicos y regímenes de vacunación. Métodos: Estudio transversal que incluyó sujetos con antecedentes de infección SARS-CoV-2, tanto no vacunados como vacunados contra la COVID-19. Se recogieron tres muestras: lágrima, saliva y sangre. Se analizaron IgA e IgG frente a S-1 SARS-CoV-2 con ELISA semicuantitativo. Resultados: 30 sujetos, edad media 36,4±10, varones 13/30 (43,3%) con historia de infección SARS-CoV-2 leve. 13/30 (43,3%) habían recibido un régimen de 2 dosis y 13/30 (43,3%) un régimen de 3 dosis de vacunación anti-COVID-19, 4/30 (13,3%) no vacunados. Todos los sujetos con vacunación completa presentaron IgA detectable en los tres biofluidos. Entre los no vacunados, se detectó IgA en 3/4 sujetos en lágrima y saliva, mientras que no se detectó IgG. No se observaron diferencias entre la pauta de vacunación de 2 y 3 dosis según los títulos IgA-IgG. Conclusiones: Anticuerpos IgA e IgG del SARS-CoV-2 están presentes en lágrima de pacientes con antecedentes de COVID-19 leve, lo que destaca el papel de la superficie ocular como primera línea de defensa frente a la infección. La mayoría de los sujetos no vacunados presentaron IgA a largo plazo en lágrima y saliva. La inmunización híbrida (infección natural más vacunación) parece potenciar las respuestas IgG mucosas y sistémicas. No se observaron diferencias entre la pauta de 2 y 3 dosis.

Effects of COVID-19 pandemic on glaucoma appointment scheduling in a tertiary hospital in London, UK.

PURPOSE: To investigate the impact of the delay in patient appointments caused by the COVID-19 pandemic and the triage system on the glaucomatous disease of patients in a London tertiary hospital. METHODS: Observational retrospective study that randomly selected 200 glaucoma patients with more than 3 months of unintended delay for their post-COVID visit and other inclusion and exclusion criteria. Demographic information, clinical data, number of drugs, best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) mean deviation (MD), and global peripapillary retinal nerve fibre layer (pRNFL) thickness were obtained from the pre- and post-COVID visit. At the post-COVID visit, the clinical outcomes subjective clinical concern and change of treatment or need for surgery were also annotated. The variables were stratified by glaucoma severity (according to the MD into early, moderate and advanced) and by delay time (more and less than 12 months) and analysed using SPSS. RESULTS: We included 121 eyes (from 71 patients). The median patient age was 74 years (interquartile range -IQR- 15), 54% were males and 52% Caucasians. Different glaucoma types and all glaucoma severities were included. When data was stratified for glaucoma severity, at the pre-COVID visit, significant differences in BCVA, CCT and IOP were observed and there were significantly higher values in the early glaucoma group. The median follow-up delay was 11 months (IQR 8), did not differ between the glaucoma severity groups and did not correlate to the glaucoma severity. At the post-COVID visit, significant differences in BCVA, IOP, and Global pRNFL thickness were observed between the glaucoma severity groups, as lower BCVA and higher IOP and pRNFL thickness were observed in the early glaucoma group. At the post-COVID visit there was cause for concern in 40 eyes: 5 were followed more closely, 22 had a change of treatment and 13 were booked for surgery (3 for cataract and 10 for glaucoma surgery). However, the number of eyes with causes for concern were similar between the glaucoma severity groups and there was no correlation between these clinical outcomes and the delay of the post-COVID visit. The number of topical hypotensive medications increased significantly after the post-COVID visit, higher number of medications were observed in the advanced glaucoma group. When differences of IOP, MD and pRNFL thickness between the pre and post-COVID visit, only the MD difference was significantly different between the glaucoma severity groups because it was higher in the severe group. When data was stratified for delay longer or shorter than 12 months, no differences were observed between the groups except at the pre-COVID visit, when the numbers of patients with MD deviation >-6 dB had longer delay time. When differences in IOP, MD and RNFL thickness were calculated, only the pRNFL thickness showed significant differences between the delay groups, because it was higher in the longer delay group. Finally, when paired analysis of the variables at the pre- and post-COVID visits, stratified by glaucoma severity and delay were conducted, although there were no significant differences in IOP in any group, the BCVA decreased significantly in the overall group and in the longer delay groups, the number of hypotensive drugs increased significantly overall and in the moderate and advanced glaucoma, the MD of the VF worsened significantly in the overall group and in the early glaucoma and longer delay groups and the pRNFL thickness decreased significantly in all groups. CONCLUSIONS: We document that delayed care impacts negatively on the glaucomatous disease of our patients because at the post-COVID visit there were reasons for clinical concern in a third of eyes that resulted in change of treatment or surgery. However, these clinical consequences were not related to IOP, glaucoma severity or delay time and reflect that the triage methods implemented worked adequately. The most sensitive parameter to indicate progression in our sample was the pRNFL thickness.

One-Year Changes in Optic Nerve Head Parameters in Recovered COVID-19 Patients.

BACKGROUND: The main purpose was to evaluate the changes in peripapillary retinal nerve fiber layer (RNFL) thickness and vessel density (VD) in post-COVID-19 patients during 12-month follow-up. METHODS: In this prospective study, patients with COVID-19 who were attended in the Hospital Clinico San Carlos (Madrid, Spain) were included. All patients underwent a complete ophthalmological examination, optic nerve head optical coherence tomography (OCT), and OCT angiography (OCTA) using the Cirrus HD-OCT 5,000 with AngioPlex OCTA 1, 3, and 12 months after laboratory-confirmed diagnosis. Sociodemographic data, medical history, disease severity, and laboratory workup were registered. RESULTS: A total of 180 eyes of 90 patients with SARS-CoV-2 infection were included; the mean age was 55.5 ± 8.9 years, and 46 patients (51%) were females. The mean visual acuity was 0.76 ± 0.16, and no abnormalities attributable to SARS-CoV-2 were detected in the ocular or fundus examination. No differences in the OCT and OCTA data were found between severity groups in each visit (all P > 0.05). Overall, there was a decrease in RNFL global thickness ( P < 0.001) from the first to the last visit, and an increase in VD and flux index was noted in some sectors at the 12-month examination. A significant correlation was detected at 12 months between vascularization parameters and RNFL thickness. CONCLUSIONS: One year after SARS-CoV-2 infection, changes in peripapillary RNFL thickness and vascularization occur, possibly indicating a recovery in such parameters.

Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review.

SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread.

Optic Nerve Head Vessel Density Assessment in Recovered COVID-19 Patients: A Prospective Study Using Optical Coherence Tomography Angiography.

PRECIS: Vascular diseases have been linked to alterations in optic nerve head perfusion. PURPOSE: The main objective was to investigate the changes in peripapillary vessel density (VD) in post coronavirus disease (COVID-19) patients. METHODS: In this prospective pilot exploratory study, patients with COVID-19 that were attended in the Emergency Department of Hospital Clinico San Carlos (Madrid) were included. All patients underwent optic nerve head optical coherence tomography angiography using the Cirrus HD-OCT 500 with AngioPlex OCTA (Zeiss, Dublin, CA) 4 and 12 weeks after diagnosis by positive reverse transcriptase-polymerase chain reaction test from nasopharyngeal swab at the Emergency Department. Sociodemographic data, medical history, disease severity, and laboratory work-up were collected. RESULTS: One hundred and eighty eyes of 90 patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection were included. None of the patients reported visual changes. Severe patients were older, more frequently hispanic, dyslipidemic, and presented lower lymphocytes counts, as well as increased ferritin, D-dimer, fibrinogen, and international normalized ratio levels. No changes in optic nerve head vascularization were observed when both visits were compared. No correlation was found between VD and clinical parameters, disease severity and laboratory work-up. CONCLUSIONS: Changes to peripapillary VD were not observed in patients with COVID-19 in the early months following diagnosis.

Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection.

PURPOSE: To describe macular vessel density and perfusion in COVID-19 patients using coherence tomography angiography (OCTA) and to investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters. METHODS: Cross-sectional analysis conducted at the Hospital Clinico San Carlos in Madrid, Spain. Patients with laboratory-confirmed COVID-19 that were attended in the Emergency Department (ED) from March 23 to March 29, 2020 were included. Fundus examination and OCTA were performed 4 weeks after being attended in ED. Macular OCTA parameters were analyzed and correlated with clinical (severity and hypoxemia- oxygen saturation < 92%) and laboratory parameters during hospital stay (D-Dimer-DD, lactate dehydrogenase-LDH and C-reactive protein-CRP). RESULTS: 80 patients were included, mean age 55(SD9) years old; 46.3% male. We reported macular vessel density and perfusion measurements in COVID-19 patients. Those patients with D-Dimer ≥ 500 ng/ml during SARS-CoV-2 infection had a decrease of central vessel density (mean difference 2.2; 95%CI 0.4-3.9) and perfusion density (mean difference 4.9; 95%CI 0.9-8.9) after the acute phase of COVID-19. These variations of vessel density and perfusion density were not documented in patients with LDH ≥ 500 U/L, CRP ≥ 10 mg/L and hypoxemia. CONCLUSIONS: COVID-19 patients showed short-term retinal vasculature abnormalities which may be related to a prothrombotic state associated with SARS-CoV-2 infection. Since the retinal microvasculature shares many morphological and physiological properties with the vasculature of other vital organs, further research is needed to establish whether patients with increased D-Dimer levels require more careful assessment and follow-up after COVID-19.

OBJETIVO: Evaluar la densidad vascular (DV) y la perfusión vascular (PV) retiniana en pacientes con COVID-19 mediante una angiografía por tomografía de coherencia óptica (OCTA), e investigar si existe una correlación entre las anomalías vasculares de la retina y los parámetros clínicos y de laboratorio. MÉTODOS: Análisis transversal realizado en el Hospital Clínico San Carlos, Madrid. Se incluyeron pacientes con diagnóstico confirmado de COVID-19 atendidos en el Servicio de Urgencias (SU) del 23 al 29 de marzo del 2020. Se realizó una exploración oftalmológica y OCTA cuatro semanas después de acudir al SU. Se analizaron los parámetros maculares de OCTA y se correlacionaron con parámetros clínicos (gravedad e hipoxemia-saturación de oxígeno < 92%) y de laboratorio durante la estancia hospitalaria (dímero D [DD], lactato deshidrogenasa [LDH] y proteína C reactiva [CRP]. RESULTADOS: Se incluyeron 80 pacientes, edad media 55 (DE nueve) años; 46,3% hombres. Las personas con DD > 500 ng/mL durante la infección por SARS-CoV-2 tuvieron una disminución de la DV central (diferencia de medias 2,2; IC 95% 0,4 a 3,9) y PV central (diferencia de medias 4,9; IC 95% 0,9 a 8,9) después de la fase aguda de COVID-19. Estas variaciones no se documentaron en los pacientes con LDH > = 500 U/L, CRP > = 10 mg/L y con hipoxemia. CONCLUSIONES: Los pacientes con COVID-19 mostraron anomalías de la vasculatura retiniana a corto plazo que pueden estar relacionadas con un estado protrombótico asociado con la infección por SARS-CoV-2. Dado que la microvasculatura de la retina comparte muchas propiedades morfológicas y fisiológicas con la vasculatura de otros órganos vitales, es necesario seguir investigando para determinar si los pacientes con niveles elevados de DD requieren una evaluación y un seguimiento más cuidadoso.

Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography.

PURPOSE: Thrombotic events (TE) represent one of the major complications of SARS-CoV-2 infection. The objective is to evaluate vessel density (VD) and perfusion density (PD) by optical coherence tomography angiography (OCTA) in COVID-19 patients, and compare the findings with healthy controls. The secondary objective is to evaluate if there are differences in OCTA parameters between COVID-19 patients with and without associated TE. METHODS: Cross-sectional case-control study that included patients with laboratory-confirmed diagnosis of COVID-19 with and without TE related to the infection and age-matched healthy controls. Ophthalmological examination and OCTA were performed 12 weeks after diagnosis. Demographic data and medical history were collected. Macular OCTA parameters in the superficial retinal plexus were analyzed according to ETDRS sectors. RESULTS: Ninety patients were included, 19 (20%) COVID-19 patients with associated TE, 47 (49.5%) COVID-19 patients without TE, and 29 (30.5%) healthy controls. Fifty-three (55.7%) were male, mean age 54.4 (SD 10.2) years. COVID-19 patients presented significantly lower VD than healthy controls: central (p = 0.003), inner ring (p = 0.026), outer ring (p = 0.001). PD was also significantly decreased: outer ring (p = 0.003), full area (p = 0.001). No differences in OCTA parameters were found between COVID-19 patients with and without TE. CONCLUSIONS: OCTA represents a promising tool for the in vivo assessment of microvascular changes in COVID-19. Patients with SARS-CoV-2 infection show lower VD and PD compared to healthy controls. However, no differences were found between COVID-19 when considering TE. Prospective studies are required to further evaluate the retinal microvascular involvement of SARS-CoV-2 and its impact on the vasculature of other organs.

Optic nerve and macular optical coherence tomography in recovered COVID-19 patients.

PURPOSE: To investigate the peripapillary retinal nerve fiber layer thickness (RNFLT), macular RNFLT, ganglion cell layer (GCL), and inner plexiform layer (IPL) thickness in recovered COVID-19 patients compared to controls. METHODS: Patients previously diagnosed with COVID-19 were included, while healthy patients formed the historic control group. All patients underwent an ophthalmological examination, including macular and optic nerve optical coherence tomography. In the case group, socio-demographic data, medical history, and neurological symptoms were collected. RESULTS: One hundred sixty patients were included; 90 recovered COVID-19 patients and 70 controls. COVID-19 patients presented increases in global RNFLT (mean difference 4.3; CI95% 0.8 to 7.7), nasal superior (mean difference 6.9; CI95% 0.4 to 13.4), and nasal inferior (mean difference 10.2; CI95% 2.4 to 18.1) sectors of peripapillary RNFLT. Macular RNFL showed decreases in COVID-19 patients in volume (mean difference -0.05; CI95% -0.08 to -0.02), superior inner (mean difference -1.4; CI95% -2.5 to -0.4), nasal inner (mean difference -1.1; CI95% -1.8 to -0.3), and nasal outer (mean difference -4.7; CI95% -7.0 to -2.4) quadrants. COVID-19 patients presented increased GCL thickness in volume (mean difference 0.04; CI95% 0.01 to 0.07), superior outer (mean difference 2.1; CI95% 0.8 to 3.3), nasal outer (mean difference 2.5; CI95% 1.1 to 4.0), and inferior outer (mean difference1.2; CI95% 0.1 to 2.4) quadrants. COVID-19 patients with anosmia and ageusia presented an increase in peripapillary RNFLT and macular GCL compared to patients without these symptoms. CONCLUSIONS: SARS-CoV-2 may affect the optic nerve and cause changes in the retinal layers once the infection has resolved.

Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection.

PURPOSE: To describe macular vessel density and perfusion in COVID-19 patients using coherence tomography angiography (OCTA) and to investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters. METHODS: Cross-sectional analysis conducted at the Hospital Clinico San Carlos in Madrid, Spain. Patients with laboratory-confirmed COVID-19 that were attended in the Emergency Department (ED) from March 23 to March 29, 2020 were included. Fundus examination and OCTA were performed 4 weeks after being attended in ED. Macular OCTA parameters were analyzed and correlated with clinical (severity and hypoxemia- oxygen saturation<92%) and laboratory parameters during hospital stay (D-Dimer-DD, lactate dehydrogenase-LDH and C-reactive protein-CRP). RESULTS: 80 patients were included, mean age 55(SD9) years old; 46.3% male. We reported macular vessel density and perfusion measurements in COVID-19 patients. Those patients with D-Dimer≥500ng/ml during SARS-CoV-2 infection had a decrease of central vessel density (mean difference 2.2; 95%CI 0.4-3.9) and perfusion density (mean difference 4.9; 95%CI 0.9-8.9) after the acute phase of COVID-19. These variations of vessel density and perfusion density were not documented in patients with LDH≥500U/L, CRP≥10mg/L and hypoxemia. CONCLUSIONS: COVID-19 patients showed short-term retinal vasculature abnormalities which may be related to a prothrombotic state associated with SARS-CoV-2 infection. Since the retinal microvasculature shares many morphological and physiological properties with the vasculature of other vital organs, further research is needed to establish whether patients with increased D-Dimer levels require more careful assessment and follow-up after COVID-19.