RESUMO
INTRODUCTION: Joubert syndrome (JS) is a recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including optic nerve morphologic abnormalities. The function of the visual pathways, including the optic nerve, can be objectively evaluated by visual evoked potential (VEP) recordings. Our work aims to employ VEP to evaluate the neural conduction along the visual pathways in JS patients with or without optic nerve morphologic abnormalities (ONMA). METHODS: In this observational and prospective study, 18 children with genetic diagnosis of JS (mean age 8.78 ± 5.87 years) and 17 healthy age-similar control subjects (control group, 9.05 ± 6.02 years) were enrolled. Based on presence/absence of ONMA at fundus examination, JS patients were divided into two groups: the JS-A group (eight patients with ONMA) and JS-N group (ten patients without ONMA). Following the ISCEV standards, pattern VEPs were recorded in patients and controls in response to 60' and 15' checks to obtain a prevalent activation of large or small axons, respectively. RESULTS: Compared to controls, both the JS-A and JS-N groups showed significant abnormalities in 60' and 15' VEP implicit time and amplitude. Only in the JS-N group were values of 15' VEP implicit significantly correlated with the corresponding values of visual acuity. CONCLUSIONS: Our results suggest that a visual pathways dysfunction (of both large and small axons) detectable by VEP may occur in JS patients regardless of the presence of ONMA. Since clinical trials are envisaged in the near future to address JS-related ocular problems, our results might provide information about the potential usefulness of VEP recordings to assess the efficacy of treatments targeted to improve the visual pathways' function.
Assuntos
Anormalidades Múltiplas , Anormalidades do Olho , Doenças Renais Císticas , Adolescente , Cerebelo/anormalidades , Criança , Pré-Escolar , Eletrorretinografia , Potenciais Evocados Visuais , Anormalidades do Olho/diagnóstico , Humanos , Doenças Renais Císticas/diagnóstico , Estudos Prospectivos , Retina/anormalidades , Vias VisuaisRESUMO
INTRODUCTION: Joubert syndrome (JS) is an autosomal recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including congenital retinal dystrophy. The function of different retinal elements (rod, cone, bipolar cells) can be objectively evaluated by electroretinogram (ERG) recordings. Our work aims to evaluate the retinal function (by ERG recordings) in patients with JS with or without congenital retinal dystrophy. In addition, since clinical trials should be performed in the near future in JS, our results could provide information about the possible usefulness of ERG recordings in the assessment of the efficacy of treatments targeted to improve the retinal involvement. METHODS: In this observational and prospective study, 24 children with genetic identification for JS (mean age 10.75 ± 6.59 years) and 25 healthy age-similar normal control subjects (control group, mean age 10.55 ± 3.76 years) were enrolled. On the basis of the presence/absence of retinal dystrophy at fundus examination, patients with JS were divided into two groups: patients with JS with retinal dystrophy (16 children, mean age 11.00 ± 6.74 years, providing 16 eyes; JS-RD group) and patients with JS without retinal dystrophy (8 children, mean age 10.50 ± 6.45 years, providing 8 eyes; JS-NRD group). In patients with JS and controls, visual acuity (VA), dark-adapted, light-adapted, and 30-Hz flicker ERGs were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. RESULTS: When compared to controls, patients in the JS-RD and JS-NRD groups showed significant abnormalities of the values of dark-adapted, light-adapted, and 30-Hz flicker ERG parameters. The ERG and VA changes were not significantly correlated. CONCLUSIONS: Our results suggest that a dysfunction of photoreceptors and bipolar cells occurs in patients with JS with or without retinal dystrophy. The retinal impairment can be detected by ERG recordings and this method should be proposed to evaluate the effectiveness of adequate treatment targeted to improve the retinal impairment in patients with JS.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/fisiopatologia , Cerebelo/anormalidades , Eletrorretinografia/métodos , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/fisiopatologia , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/fisiopatologia , Retina/anormalidades , Retina/fisiopatologia , Acuidade Visual/fisiologia , Adolescente , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Itália , Masculino , Estudos ProspectivosRESUMO
INTRODUCTION: Binocular indirect ophthalmoscopy (BIO) is fundamental for screening of retinopathy of prematurity (ROP). Digital retinal imaging devices with fluorescein angiography (FA) proved to be useful in screening and management of ROP. FA provides valuable additional information that is not detectable through ophthalmoscopy. FA images are relatively easy to interpret even by personnel without specific experience in ROP. The aim of this study is to evaluate reproducibility of FA for the screening and follow-up of ROP. METHODS: A total of 106 pairs of FA images of 30 eyes of 15 premature infants with stage II ROP were evaluated by 5 ophthalmologists: 2 experts, 2 non-experts, and 1 expert in reading FA in adult patients. Each operator gave a score to each of following parameters: leakage, ischemic areas, peripheral plus disease and vascular anomalies. The images were reviewed twice. Intra- and inter-concordance between the readers of the FA findings was evaluated by the means of Cohen's kappa coefficient (κ). RESULTS: The intra-operator concordance was very good (κ > 0.81) for all FA findings. Inter-operator concordance was good (κ > 0.41) for all operators and all FA findings. Global concordance was: substantial (intra-inter readers: κ > 0.61) for leakage, ischemic areas, and plus disease; almost perfect (κ > 0.81) for vascular anomalies; and moderate (κ = 0.41-0.60) for continuity/discontinuity of the ischemic areas. Total FA score was directly correlated to the percentage of treatment: a score ≥ 7 was correlated with 100% treatment and a score ≤ 3 with no treatment. Treatment timing was inversely correlated to FA score: a score ≥ 8 was correlated with a timely treatment (≤ 6 days), and a score ≤ 7 was correlated with a delayed treatment (< 10 days). CONCLUSION: This study showed that FA represents a reproducible imaging technique. It is useful for detecting ROP progression, and to define the treatment timing and type.
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Angiofluoresceinografia/métodos , Angiofluoresceinografia/estatística & dados numéricos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Oftalmoscopia/métodos , Oftalmoscopia/estatística & dados numéricos , Retinopatia da Prematuridade/diagnóstico , Peso ao Nascer , California/epidemiologia , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Reprodutibilidade dos Testes , Retinopatia da Prematuridade/epidemiologiaRESUMO
BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (pâ¯=â¯0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBCâ¯≥â¯12,800/mm3, CRPâ¯≥â¯130â¯mg/L, and procalcitoninâ¯≥â¯1.7â¯ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkersâ¯<â¯cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBCâ¯≥â¯10,535/mm3, CRPâ¯≥â¯85â¯mg/dL, and procalcitoninâ¯≥â¯0.4â¯ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkersâ¯<â¯cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.
Assuntos
Proteína C-Reativa/análise , Endocardite Bacteriana , Contagem de Leucócitos/métodos , Pró-Calcitonina/sangue , Infecções Estafilocócicas , Staphylococcus aureus/isolamento & purificação , Idoso , Biomarcadores/sangue , Testes Diagnósticos de Rotina/métodos , Endocardite Bacteriana/sangue , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Itália/epidemiologia , Masculino , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/diagnósticoRESUMO
PURPOSE: Joubert syndrome (JS) is an inherited autosomal recessive or X-lined disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features. It is estimated that retinal dystrophy is present in association with the typical neurological findings in about one-third of the patients. The aim of this study is to better characterize the macular region in JS patients with and without retinal dystrophy. METHODS: We describe six individuals affected by JS as demonstrated by the presence of the typical "molar tooth sign" on MRI. The presence of retinal dystrophy was assessed by fundus examination and electrophysiology by means of full-field electroretinogram (ERG) and visual evoked potentials (VEP) at five spatial frequencies (300-15 min of arc). The macular region was examined with spectral domain optical coherence tomography (SD-OCT). All the exams were performed in awake conditions. All the patients underwent next-generation-sequencing analysis of known JS genes. RESULTS: Pathogenic biallelic variants in either the INPP5E gene or the AHI1 gene were detected in two pairs of siblings, all positive for retinal dystrophy. Genetic testing yielded no results in the remaining two patients, one with bilateral coloboma and retinal dystrophy and the other with normal fundus appearance. Decimal best-corrected visual acuity was between 0.1 and 1.0. In the two pairs of siblings, SD-OCT revealed a posterior staphyloma centred on the fovea, in one case associated with cystoid macular oedema. Macular morphology was just slightly altered in the fifth patient and completely normal in the last patient. Refractive error was between + 2.50 diopter sphere (DS) and - 8 DS and - 4 diopter cylinder ax 45°. ERG waves were markedly lower than the normal limits in both scotopic and photopic components in the two pairs of siblings and in the fifth subject, with VEP P100 latencies and amplitudes delayed and reduced in all spatial frequencies. ERG and VEP were within normal limits in the last patient. CONCLUSIONS: To our knowledge, macular staphyloma has not been described before in JS. Further work is warranted to assess the true prevalence of staphyloma in JS and its connection to retinal dystrophy.
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Cerebelo/anormalidades , Anormalidades do Olho/complicações , Doenças Renais Císticas/complicações , Macula Lutea/patologia , Retina/anormalidades , Distrofias Retinianas/complicações , Anormalidades Múltiplas/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transporte Vesicular , Adolescente , Adulto , Criança , Dilatação Patológica , Eletrorretinografia , Potenciais Evocados Visuais , Anormalidades do Olho/diagnóstico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Renais Císticas/diagnóstico , Macula Lutea/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Monoéster Fosfórico Hidrolases/genética , Retina/fisiopatologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto JovemRESUMO
PURPOSE: To evaluate accuracy and inter-rater reliability of RetCam fundus images and digital camera fluorangioscopic images in acute retinopathy of prematurity (ROP) by comparing diagnoses given by trainee ophthalmologists with those provided by expert ophthalmologists. â© METHODS: This is a multicenter retrospective observational study of diagnostic data from 48 eyes of 24 premature infants with classical ROP, stage II, as evaluated by RetCam 3 and fluorescein angiography (FA). Average gestational age was 25.4 weeks, average weight 804.7 g. A staging grid (with ocular fundus divided into 3 concentric zones) and 24 15° sectors centered around the optic papilla were superimposed on 360° retina photomontages (Photoshop) made from RetCam and FA images. Non expert vs expert diagnosis agreement was measured for each sector by means of Cohen kappa (Fleiss, 1981).â© RESULTS: A high degree of concordance was found. Inter-rater agreement between expert and non expert interpretations of retinal photomontages was greater for fluorangiographic images than for RetCam images, with κ = 0.61-1 for 120/152 (78.9%) sectors examined on the RetCam images and κ = 0.61-1 for 168/198 (84.8%) sectors examined on the FA images.â© CONCLUSIONS: The FA images appear to be easier to interpret than RetCam images, both by expert and non expert ophthalmologists. The results confirm that FA is a good examination technique with a high degree of reliability, even where trainee practitioners are involved. This suggests that retinopathy management can be improved by entrusting diagnostic responsibilities to trainee ophthalmologists, in order to extend access to correct diagnosis, recognition of threshold lesions, and prompt treatment.
Assuntos
Angiofluoresceinografia/métodos , Internato e Residência/normas , Oftalmologia/normas , Retinopatia da Prematuridade/diagnóstico , Competência Clínica , Educação de Pós-Graduação em Medicina , Feminino , Fluoresceína , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Variações Dependentes do Observador , Oftalmologia/educação , Fotografação , Reprodutibilidade dos Testes , Retinopatia da Prematuridade/classificação , Estudos RetrospectivosRESUMO
AIM: We set out to describe 17 patients with septo-optic dysplasia (SOD), focusing on the little-explored neurological, cognitive, and neuro-ophthalmological components. A further aim was to identify possible clinical correlations and phenotypic characteristics within the diagnostic spectrum. METHOD: We collected clinical-instrumental data (from the history, general and neurological examination, developmental assessment, and neuro-ophthalmological, neuroradiological, neurophysiological, and endocrinological evaluations) on nine males and eight females (mean age 34.4mo, SD 31.6; range 4mo-9y 6mo) diagnosed with SOD who were referred to our Centre of Child Neuro-ophthalmology between 1999 and 2010. RESULTS: We observed a heterogeneous clinical spectrum characterized by nervous system, visual, and endocrine dysfunctions; optic nerve involvement was present in all 17 children, midline brain defects in 14, and cortical developmental malformations in seven. Developmental/cognitive delay and relational and communication difficulties were observed in eight and seven children, respectively, and reduced visual acuity and oculomotor dysfunction were observed in all. Pituitary hormone deficiencies were present in nine children. INTERPRETATION: Nervous system involvement emerged as a key feature of SOD. As part of a holistic approach to the disease, particular attention should be paid to this aspect. The emergence of new clinical correlations and correlations between clinical features and three SOD subtypes opens the way for better clarification of this disease and, therefore, more targeted diagnosis, follow-up, and care of affected children.
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Encéfalo/anormalidades , Doenças do Sistema Nervoso/diagnóstico , Doenças da Hipófise/diagnóstico , Displasia Septo-Óptica/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/etiologia , Masculino , Doenças do Sistema Nervoso/etiologia , Doenças do Nervo Oculomotor/diagnóstico , Doenças do Nervo Oculomotor/etiologia , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Doenças da Hipófise/etiologia , Hormônios Hipofisários/deficiência , Displasia Septo-Óptica/classificação , Displasia Septo-Óptica/fisiopatologia , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologiaRESUMO
PURPOSE: To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis. METHODS: DNA samples from 95 patients with LCA were analyzed by using a microarray chip containing disease-associated sequence variants in eight LCA genes. In addition, all patients in whom no mutations were identified by microarray were subjected to sequence analysis of the CEP290 gene. Patients with mutations identified underwent a detailed ophthalmic evaluation. RESULTS: Disease-causing mutations were identified in 28% of patients, and twelve novel variants were identified. Mutations occurred more frequently in the RPE65 (8.4%), CRB1 (7.4%), and GUCY2D (5.2%) genes. Mutations in CEP290 were found in only 4.2% of the patients analyzed. Clinical assessment of patients carrying RPE65 or CRB1 mutations revealed the presence of retained visual capabilities in the first decade of life. RPE65 mutations were almost always associated with normal macular thickness, as assessed by optical coherence tomography (OCT), whereas CRB1 mutations were associated with reduced retinal thickness and a coarsely laminated retina. Fundus autofluorescence was mostly observed in patients with RPE65 and GUCY2D mutations and was not elicitable in patients carrying CRB1. CONCLUSIONS: RPE65 gene mutations represented a significant cause of LCA in the Italian population, whereas GUCY2D and CEP290 mutations had a lower frequency than that found in other reports. This finding suggests that the genetic epidemiology of LCA in Italy is different from that reported in the United States and in northern European countries. Autofluorescence in patients with RPE65 mutations was more frequently associated with preserved retinal thickness, which suggests that these mutations are not associated with progression of retinal degeneration. Therefore, normal retinal thickness (identified with OCT) and fundus autofluorescence may be the means with which to identify patients with LCA who carry RPE65 mutations, which are expected to be a potential gene therapy target in the near future.