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.

Long-Term Consequences of COVID-19 Lockdown in Neovascular AMD Patients in Spain: Structural and Functional Outcomes after 1 Year of Standard Follow-Up and Treatment.

Consequences of the COVID-19 pandemic on medical care have been extensively analyzed. Specifically, in ophthalmology practice, patients suffering age-related macular degeneration (AMD) represent one of the most affected subgroups. After reporting the acute consequences of treatment suspension in neovascular AMD, we have now evaluated these same 242 patients (270 eyes) to assess if prior functional and anatomical situations can be restored after twelve months of regular follow-up and treatment. We compared data from visits before COVID-19 outbreak and the first visit after lockdown with data obtained in subsequent visits, until one year of follow-up was achieved. For each patient, rate of visual loss per year before COVID-19 pandemic, considered "natural history of treated AMD", was calculated. This rate of visual loss significantly increased during the lockdown period and now, after twelve months of regular follow-up, is still higher than before COVID outbreak (3.1 vs. 1.6 ETDRS letters/year, p < 0.01). Percentage of OCT images showing active disease is now lower than before the lockdown period (51% vs. 65.3%, p = 0.0017). Although anatomic deterioration, regarding signs of active disease, can be apparently fully restored, our results suggest that functional consequences of temporary anti-VEGF treatment suspension are not entirely reversible after 12 months of treatment, as BCVA remains lower and visual loss rate is still higher than before the COVID-19 pandemic.

Retinal and peripapillary vessel density increase in recovered COVID-19 children by optical coherence tomography angiography.

PURPOSE: To evaluate retinal vascular changes in children who have recovered from coronavirus disease (COVID-19) using optical coherence tomography angiography (OCTA) and to compare the results with age-matched healthy children. METHODS: In this cross-sectional case-control study, children 6-18 years of age with laboratory-confirmed SARS-CoV-2 infection were compared with historic healthy controls. All participants underwent ophthalmological examination, including fundus photography and OCTA of the macular region and optic disk. COVID-19 children were examined 4-8 weeks after COVID-19 diagnoses. Demographic data, medical history, and COVID-19 symptoms were noted. OCTA parameters in the superficial capillary plexus (SCP) were analyzed according to ETDRS sectors and peripapillary quadrants. RESULTS: A total of 72 patients were included: 27 recovered COVID-19 children and 45 controls. Mean age for cases was 11.96 ± 3.8 years (18 females [66%]); for controls, 11.02 ± 2.0 years (29 females [64%]). Macular OCTA of the SCP showed a significant increase in retinal vessel density (VD) in recovered COVID-19 children compared with healthy controls in the inner ring (P = 0.001). Macular perfusion density (mPD) was also increased in the inner ring (P = 0.001). Peripapillary OCTA evidenced a significant higher flux index (FI) in all four quadrants (P < 0.001). CONCLUSIONS: Recovered COVID-19 children present increased retinal VD, mPD, and peripapillary FI shortly after recovery. Since the retinal vasculature is considered a unique window to assess microvascular changes, these findings may represent a potential in vivo biomarker of vascular abnormalities in COVID-19 children in other organs.

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.

Retinal nerve fibre layer and ganglion cell layer changes in children who recovered from COVID-19: a cohort study.

OBJECTIVE: To investigate the optic nerve and macular parameters of children who recovered from COVID-19 compared with healthy children using optical coherence tomography (OCT). DESIGN: Cohort study. SETTING: Hospital Clinico San Carlos, Madrid. PATIENTS: Children between 6 and 18 years old who recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection and historical controls were included. INTERVENTIONS: All patients underwent an ophthalmological examination, including macular and optic nerve OCT. Demographic data, medical history and COVID-19 symptoms were noted. MAIN OUTCOME MEASURES: Peripapillary retinal nerve fibre layer thickness, macular retinal nerve fibre layer thickness, macular ganglion cell layer thickness and retinal thickness. RESULTS: 90 patients were included: 29 children who recovered from COVID-19 and 61 controls. Patients with COVID-19 presented an increase in global peripapillary retinal nerve fibre layer thickness (mean difference 7.7; 95% CI 3.4 to 12.1), temporal superior (mean difference 11.0; 95% CI 3.3 to 18.6), temporal inferior (mean difference 15.6; 95% CI 6.5 to 24.7) and nasal (mean difference 9.8; 95% CI 2.9 to 16.7) sectors. Macular retinal nerve fibre layer analysis showed decreased thickness in the nasal outer (p=0.011) and temporal inner (p=0.036) sectors in patients with COVID-19, while macular ganglion cell layer thickness increased in these sectors (p=0.001 and p=0.015, respectively). No differences in retinal thickness were noted. CONCLUSIONS: Children with recent history of COVID-19 present significant changes in peripapillary and macular OCT analyses.

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.