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We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health followup; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke.
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Epidemias , Fiebre Hemorrágica Ebola/complicaciones , Fiebre Hemorrágica Ebola/epidemiología , Trastornos Migrañosos/etiología , Enfermedades del Sistema Nervioso Periférico/etiología , Accidente Cerebrovascular/etiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Sierra Leona/epidemiología , Adulto JovenRESUMEN
We conducted a case-control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5% CI 63%-85.7%) of EVD survivors and 75.5% (97.5% CI 59.1%-87.9%) of controls. Unilateral white cataracts were present in 7.4% (97.5% CI 2.4%-16.7%) of EVD survivors and no controls. Aqueous humor from 2 EVD survivors with cataract but no anterior chamber inflammation were PCR-negative for Zaire Ebola virus, permitting cataract surgery. A novel retinal lesion following the anatomic distribution of the optic nerve axons occurred in 14.6% (97.5% CI 7.1%-25.6%) of EVD survivors and no controls, suggesting neuronal transmission as a route of ocular entry.
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Ebolavirus , Fiebre Hemorrágica Ebola/complicaciones , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Sobrevivientes , Adulto , Estudios de Casos y Controles , Femenino , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/historia , Fiebre Hemorrágica Ebola/virología , Historia del Siglo XXI , Humanos , Masculino , Oftalmoscopios , Vigilancia de la Población , Prevalencia , Enfermedades de la Retina/epidemiología , Índice de Severidad de la Enfermedad , Sierra Leona/epidemiología , Agudeza Visual , Adulto JovenRESUMEN
Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index. Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centered region of interest. We analyzed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error [MAE]) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error. Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703), and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal)/0.9831, 0.9779, 0.7948 (external), respectively (all P < 0.0001). Choroidalyzer's agreement with graders was comparable to the intergrader agreement across all metrics. Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully automatic methods like Choroidalyzer could provide objectivity and standardization.
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Coroides , Tomografía de Coherencia Óptica , Humanos , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Aprendizaje Profundo , Vasos Retinianos/diagnóstico por imagen , Fóvea Central/diagnóstico por imagen , Fóvea Central/irrigación sanguínea , Adulto , Reproducibilidad de los ResultadosAsunto(s)
Ebolavirus , Fiebre Hemorrágica Ebola , Estudios de Cohortes , Humanos , Estudios Retrospectivos , Sierra Leona , SobrevivientesAsunto(s)
Fiebre Hemorrágica Ebola/epidemiología , Sobrevivientes , Brotes de Enfermedades , Humanos , LiberiaRESUMEN
ABSTRACT PURPOSE: To highlight similarities between the cross-sectional retinal lesion appearance in a patient with punctate inner choroidopathy (PIC), Ebola virus disease (EVD) retinopathy and the von Szily mouse model of herpes simplex virus type 1 (HSV) retinopathy. METHODS: Case report and cross-sectional retinal lesion comparison. RESULTS: Whilst phenotypically different on colour imaging, a near-identical lesion appearance on optical coherence tomography, characterised by a focal photoreceptor loss and distinctive V-shaped collapse of the overlying retinal layers, was observed in both PIC and EVD retinopathy. This mirrored the early histological appearance of the neuronally transmitted HSV retinopathy in a mouse model. CONCLUSIONS: Given the occurrence of this phenotypic appearance has been demonstrated in an animal model where the viral pathophysiological mechanism is known, together with its observation in EVD retinopathy with a shared, hypothesised neurotropic retinal pathogenesis, the potential of a common pathophysiology accounting for the appearance in PIC lesions is a possibility which may provide a potential avenue for future research.
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Fiebre Hemorrágica Ebola , Herpes Simple , Enfermedades de la Retina , Síndromes de Puntos Blancos , Animales , Ratones , Estudios Transversales , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodosRESUMEN
PURPOSE: To assess the efficacy of treatment on acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinopathy (RPC). METHODS: Cases were identified from three UK uveitis centers. Retrospective analysis of visual acuity recovery; OCT structural outcomes; and retinal lesion quantification in observed and treated cases of APMPPE/RPC. RESULTS: There were nine APMPPE and three RPC cases. Out of 12 patients, six were female. Median age: 26.5 years (range, 20-57 years). Four cases (six eyes) were observed, and eight cases (15 eyes) received corticosteroids ± immunosuppression. 4/4 observed and 6/10 treated foveal involving eyes regained 0.00 LogMAR vision. Observed lesions achieved more favorable anatomical outcomes. New lesions post-presentation developed in 1/6 (16%) observed eye versus 10/15 (66%) treated eyes. In three cases, a delayed, rebound lesion occurrence was observed post-high-dose corticosteroids. CONCLUSIONS: While subject to potential treatment bias, in this small case series, natural history alone appears non-inferior to corticosteroid treatment.
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Purpose: To reassess the underlying pathophysiology of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinitis (RPC) through comparison with the non-inoculated eye of the von Szily animal model of neurotropic viral retinal infection. Methods: Narrative review. Results: Literature reports of isolated neurotropic viral entities and rising serological viral titers in APMPPE after presentation support a potential direct infective etiology. In general, viral transport along axons results in mitochondrial stasis and disruption of axoplasmic flow. Clinical manifestations of axoplasmic flow disruption in APMPPE/RPC may signify the passage of virus along the neuronal pathway. From a case series of 11 patients, we demonstrate a timely, spatial, and proportional association of optic disc swelling with APMPPE lesion occurrence. Signs within the inner retina appear to precede outer retinal lesions; and acute areas of outer nuclear layer (ONL) hyperreflectivity appear to be the result of coalescence of multiple hyperreflective foci resembling axonal spheroids (which occur as a consequence of axoplasmic disruption) and follow the Henle fiber layer neurons. Underlying areas of retinal pigment epithelium (RPE) hyper-autofluorescence follow ONL hyperreflectivity and may signify localized infection. Areas of apparent choriocapillaris hypoperfusion mirror areas of RPE/Bruch's membrane separation and appear secondary to tractional forces above. Increases in choroidal thickness with lesion occurrence and focal areas of choriocapillaris hypoperfusion are observed in both APMPPE/RPC and the von Szily model. Conclusions: The neurotrophic infection model provides significant advantages over the existing primary choriocapillaris ischemia hypothesis to account for the range of imaging signs observed in APMPPE and RPC.
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Importance: The 2-year ophthalmic sequelae of Ebola virus disease (EVD) in survivors of the 2013 to 2016 epidemic is unknown and may have public health implications for future outbreaks. Objective: To assess the potential for uveitis recurrence, the behavior of dark without pressure, and visual outcomes in a cohort of Sierra Leonean survivors of EVD 2 years following the 2013 to 2016 Ebola epidemic. Design, Setting, and Participants: Prospective, 1-year observational cohort study performed between 2016 and 2017 at 34 Military Hospital, Freetown, Sierra Leone. Participants included survivors of EVD who reported ocular symptoms since Ebola treatment unit discharge and were participants of a previous case-control study. Participants were invited for ophthalmic reexamination and finger-prick blood sampling for immunoglobulin G (IgG) to Toxoplasma gondii and HIV. Exposures: Ebola virus disease. Main Outcomes and Measures: Primary outcome measure: comparative ultra-widefield retinal imaging. Secondary outcome measures: visual acuity and detection of IgG to T gondii and HIV. Results: Of 57 survivors of EVD who underwent repeated ophthalmic evaluation, 37 were women (64.9%). Mean (SD) age was 31.9 (11.1) years. Median interval between first and last examination was 370 days (interquartile range [IQR], 365-397.5 days), and median time from discharge to last examination was 779 days (IQR, 732-821 days). Fifteen eyes of 10 survivors (17.5%) had retinal lesions secondary to EVD. No new EVD-associated retinal lesions were observed. Two survivors (3.5%) developed new posterior uveitis resembling toxoplasmosis chorioretinitis and 41 (73%) were seropositive for T gondii IgG. Areas of dark without pressure were observed either confined to the perimeter of Ebola retinal lesions (n = 7) and non-Ebola lesions (n = 2), involving extensive retinal areas adjacent to Ebola retinal lesions (n = 4) and non-Ebola lesions (n = 2) or in isolation (n = 6). Both expansion and regression of areas of dark without pressure were observed over the study period. Best eye-presenting visual acuity had mild or no visual impairment in 55 survivors (96.4%) 2 years following discharge. Conclusions and Relevance: Vision was maintained in survivors of EVD 2 years following discharge. Evolving regions of dark without pressure may be associated with EVD retinal lesions and might suggest the presence of an ongoing intraretinal stimulus, which may be associated with infective etiology. Treatment strategies should account for the possibility of toxoplasmosis chorioretinitis recurrence within survivors of EVD.
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Infecciones Virales del Ojo/diagnóstico , Fiebre Hemorrágica Ebola/diagnóstico , Enfermedades de la Retina/diagnóstico , Sobrevivientes , Uveítis Posterior/diagnóstico , Adulto , Anticuerpos Antiprotozoarios/sangre , Estudios de Casos y Controles , Coriorretinitis/diagnóstico , Coriorretinitis/epidemiología , Coriorretinitis/parasitología , Ebolavirus , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/epidemiología , Infecciones Parasitarias del Ojo/parasitología , Infecciones Virales del Ojo/epidemiología , Femenino , Estudios de Seguimiento , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Inmunoglobulina G/sangre , Masculino , Estudios Prospectivos , Enfermedades de la Retina/epidemiología , Sierra Leona/epidemiología , Tomografía de Coherencia Óptica , Toxoplasma/inmunología , Uveítis Posterior/epidemiología , Agudeza Visual/fisiologíaRESUMEN
Importance: Differentiation between Ebola retinal lesions and other retinal pathologies in West Africa is important, and the pathogenesis of Ebola retinal disease remains poorly understood. Objective: To describe the appearance of Ebola virus disease (EVD) retinal lesions using multimodal imaging to enable inferences on potential pathogenesis. Design, Setting, and Participants: This prospective case series study was carried out at 34 Military Hospital in Freetown, Sierra Leone. Ophthalmological images were analyzed from 14 consecutively identified survivors of EVD of Sierra Leonean origin who had identified Ebola retinal lesions. Main Outcomes and Measures: Multimodal imaging findings including ultra-widefield scanning laser ophthalmoscopy, fundus autofluorescence, swept-source optical coherence tomography (OCT), Humphrey visual field analysis, and spatial analysis. Results: The 14 study participants had a mean (SD) age of 37.1 (8.8) years; 6 (43%) were women. A total of 141 Ebola retinal lesions were observed in 22 of 27 eyes (81%) of these 14 survivors on ultra-widefield imaging. Of these, 41 lesions (29.1%) were accessible to OCT imaging. Retinal lesions were predominantly nonpigmented with a pale-gray appearance. Peripapillary lesions exhibited variable curvatures in keeping with the retinal nerve fiber layer projections. All lesions respected the horizontal raphe and spared the fovea. The OCT imaging demonstrated a V-shaped hyperreflectivity of the outer nuclear layer overlying discontinuities of the ellipsoid zone and interdigitation zone in the smaller lesions. Larger lesions caused a collapse of the retinal layers and loss of retinal thickness. Lesion shapes were variable, but sharp angulations were characteristic. Perilesional areas of dark without pressure (thinned ellipsoid zone hyporeflectivity) accompanied 125 of the 141 lesions (88.7%) to varying extents. Conclusions and Relevance: We demonstrate OCT evidence of localized pathological changes at the level of the photoreceptors in small lesions among survivors of EVD with retinal lesions. The relevance of associated areas of dark without pressure remains undetermined.