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1.
N Engl J Med ; 382(4): 341-352, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31971679

RESUMEN

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Diplopía/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Exoftalmia/tratamiento farmacológico , Oftalmopatía de Graves/diagnóstico por imagen , Humanos , Análisis de Intención de Tratar , Imagen por Resonancia Magnética , Persona de Mediana Edad , Órbita/diagnóstico por imagen , Receptor IGF Tipo 1/inmunología , Autoinforme
2.
Ophthalmology ; 129(4): 438-449, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34688699

RESUMEN

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.


Asunto(s)
Exoftalmia , Oftalmopatía de Graves , Anticuerpos Monoclonales Humanizados/uso terapéutico , Diplopía , Oftalmopatía de Graves/tratamiento farmacológico , Humanos
3.
J Neuroophthalmol ; 41(4): 461-468, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33417417

RESUMEN

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials. METHODS: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on. RESULTS: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab. CONCLUSIONS: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.


Asunto(s)
Oftalmopatía de Graves , Enfermedades del Nervio Óptico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ensayos Clínicos como Asunto , Diplopía/tratamiento farmacológico , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Enfermedades del Nervio Óptico/inducido químicamente
4.
Artículo en Inglés | MEDLINE | ID: mdl-35319490

RESUMEN

Summary: Thyroid dermopathy is an uncommon manifestation of thyroid disease that impairs the quality of life in certain cases. Currently, the available treatments offer limited results and a chance of recurrence. Teprotumumab, a novel medication that results in the regression of thyroid ophthalmopathy, may have similar effects on dermopathy. We describe four patients treated with teprotumumab for their thyroid ophthalmopathy who concomitantly had dermatopathy upon initiation of their infusions. Patients improved after two to three infusions and three out of the four patients have not suffered a recurrence.Teprotumumab is a monoclonal antibody (MAB) that attenuates an inflammatory response, resulting in decreased edema and tissue expansion. Given the similarities of their pathophysiology, we believe that the resolution of thyroid dermatopathy and regression of thyroid eye disease occurs via the same mechanism. We encourage further investigation utilizing teprotumumab for patients whose dermopathy is associated with impaired quality of life. Learning points: Thyroid dermopathy (TD), an uncommon manifestation of thyroid disease, may occasionally impair function and quality of life. There are only a few treatments for TD, with limited results and high rates of recurrence. Teprotumumab is a Food and Drug Administration-approved medication used for thyroid eye disease (TED). Our patients treated with teprotumumab for TED showed improvement of TD, which demonstrates its potential use for this condition.

5.
Mult Scler ; 16(4): 412-26, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20207786

RESUMEN

BACKGROUND: Multifocal visual evoked potentials (mfVEP) measure local response amplitude and latency in the field of vision. OBJECTIVE: To compare the sensitivity of mfVEP, Humphrey visual field (HVF) and optical coherence tomography (OCT) in detecting visual abnormality in multiple sclerosis (MS) patients. METHODS: mfVEP, HVF, and OCT (retinal nerve fiber layer [RNFL]) were performed in 47 MS-ON eyes (last optic neuritis [ON] attack >or=6 months prior) and 65 MS-no-ON eyes without ON history. Criteria to define an eye as abnormal were: (1) mfVEP amplitude/latency - either amplitude or latency probability plots meeting cluster criteria with 95% specificity; (2) mfVEP amplitude or latency alone (specificity: 97% and 98%, respectively); and (3) HVF and OCT, mean deviation and RNFL thickness meeting p < 0.05, respectively. RESULTS: MfVEP (amplitude/latency) identified more abnormality in MS-ON eyes (89%) than HVF (72%), OCT (62%), mfVEP amplitude (66%) or latency (67%) alone. Eighteen percent of MS-no-ON eyes were abnormal for both mfVEP (amplitude/latency) and HVF compared with 8% with OCT. Agreement between tests ranged from 60% to 79%. mfVEP (amplitude/latency) categorized an additional 15% of MS-ON eyes as abnormal compared with HVF and OCT combined. CONCLUSIONS: mfVEP, which detects both demyelination (increased latency) and neural degeneration (reduced amplitude), revealed more abnormality than HVF or OCT in MS patients.


Asunto(s)
Potenciales Evocados Visuales , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Neuritis Óptica/diagnóstico , Tomografía de Coherencia Óptica , Pruebas del Campo Visual , Campos Visuales , Vías Visuales , Adulto , Axones/patología , Estudios de Casos y Controles , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/patología , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Vaina de Mielina/patología , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Neuritis Óptica/patología , Neuritis Óptica/fisiopatología , Estimulación Luminosa , Valor Predictivo de las Pruebas , Tiempo de Reacción , Neuronas Retinianas/patología , Sensibilidad y Especificidad , Agudeza Visual , Vías Visuales/patología , Vías Visuales/fisiopatología , Adulto Joven
6.
Curr Neurol Neurosci Rep ; 10(6): 448-58, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20835929

RESUMEN

The facial nerve (cranial nerve VII) courses a long pathway beginning in the precentral gyrus and ending at the facial muscles, lacrimal and salivary glands, and structures of the inner ear. Lesions along this pathway, clinically divided into upper and lower motor neuron lesions, present with unique characteristics that assist the physician in identifying the lesion site. The sequelae particularly of peripheral CN VII palsies, may result in significant and chronic damage to the cornea that may be challenging for the physician and patient.


Asunto(s)
Corticoesteroides/uso terapéutico , Antivirales/uso terapéutico , Parálisis de Bell/tratamiento farmacológico , Oftalmopatías/diagnóstico , Nervio Facial/patología , Parálisis Facial/diagnóstico , Parálisis de Bell/complicaciones , Oftalmopatías/complicaciones , Nervio Facial/anatomía & histología , Parálisis Facial/complicaciones , Humanos , Modelos Neurológicos , Vías Nerviosas/anatomía & histología
7.
Optom Vis Sci ; 87(8): 576-84, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20495500

RESUMEN

PURPOSE: To compare optical coherence tomography (OCT) and scanning laser polarimetry (GDx) measurements of the retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis (ON). METHODS: OCT and GDx were performed on 68 MS patients. Qualifying eyes were divided into two groups: 51 eyes with an ON history > or =6 months before (ON eyes) and 65 eyes with no history of ON (non-ON eyes). Several GDx and OCT parameters and criteria were used to define an eye as abnormal, for example, GDx nerve fiber indicator (NFI) >20 or 30, OCT average RNFL thickness, and GDx temporal-superior-nasal-inferior-temporal average (TSNIT) below 5 or 1% of the normative database of the instruments. Agreement between OCT and GDx parameters was reported as percent of observed agreement, along with the AC1 statistic. Linear regression analyses were used to examine the relationship between OCT average RNFL thickness and GDx NFI and TSNIT. RESULTS: All OCT and GDx measurements showed significantly more RNFL damage in ON than in non-ON eyes. Agreement between OCT and GDx parameters ranged from 69 to 90% (AC1 0.37 to 0.81) in ON eyes and 52 to 91% (AC1 = 0.21 to 0.90) in non-ON eyes. Best agreement was observed between OCT average RNFL thickness (p < 0.01) and NFI (>30) in ON eyes (90%, AC1 = 0.81) and between OCT average RNFL thickness (p < 0.01) and GDx TSNIT average (p < 0.01) in non-ON eyes (91%, AC1 = 0.90). In ON eyes, the OCT average RNFL thickness showed good linear correlation with NFI (R = 0.69, p < 0.0001) and TSNIT (R = 0.55, p < 0.0001). CONCLUSIONS: OCT and GDx show good agreement and can be useful in detecting RNFL loss in MS/ON eyes.


Asunto(s)
Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Neuritis Óptica/complicaciones , Polarimetría de Barrido por Laser/normas , Tomografía de Coherencia Óptica/normas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Retina/patología
8.
J Neuroophthalmol ; 30(3): 252-4, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20724944

RESUMEN

A 70-year-old woman developed progressive visual loss with compromised visual acuity and visual fields, cells in the anterior chamber and vitreous, attenuated retinal arterioles, and macular edema. She had undergone right oophorectomy and partial salpingectomy nearly 50 years earlier. Full-field and multifocal electroretinography showed waveforms of markedly attenuated amplitudes, findings consistent with cancer-associated retinopathy (CAR). Positron emission tomography revealed a nodule in the anterior wall of a right hydrosalpinx. Total laparoscopic hysterectomy yielded a neuroendocrine fallopian tube malignancy. She underwent partial treatment with paclitaxel and carboplatin that was aborted because of the development of herpes zoster infection. At 15 months following diagnosis, her ophthalmic status was stable. This is the first report of CAR in neuroendocrine carcinoma of the fallopian tube.


Asunto(s)
Carcinoma Neuroendocrino/complicaciones , Neoplasias de las Trompas Uterinas/complicaciones , Enfermedades de la Retina/etiología , Anciano , Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Femenino , Humanos , Paclitaxel/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Enfermedades de la Retina/diagnóstico por imagen , Enfermedades de la Retina/tratamiento farmacológico , Agudeza Visual/fisiología , Campos Visuales/fisiología
9.
Mult Scler ; 15(12): 1431-41, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19995841

RESUMEN

Multifocal visual evoked potentials provide a topographic measure of visual response amplitude and latency. The objective of this study was to evaluate the sensitivity and specificity of the multifocal visual evoked potential technique in detecting visual abnormalities in patients with multiple sclerosis. Multifocal visual evoked potentials were recorded from 74 patients with multiple sclerosis with history of optic neuritis (MS-ON, n = 74 eyes) or without (MS-no-ON, n = 71 eyes), and 50 normal subjects (controls, n = 100 eyes) using a 60-sector pattern reversal dartboard stimulus (VERIS). Amplitude and latency for each sector were compared with normative data and assigned probabilities. Size and location of clusters of adjacent abnormal sectors (p < 0.05) were examined. Mean response amplitudes were (+/- SE) 0.39 +/- 0.02, 0.53 +/- 0.02, and 0.60 +/- 0.01 for MS-ON, MS-no-ON, and control groups, respectively, with significant differences between all groups (p < 0.0001). Mean latencies (ms; +/-SE relative to normative data) were 12.7 +/- 1.3 (MS-ON), 4.3 +/- 1.1 (MS-no-ON), and 0.3 +/- 0.4 (controls); group differences again significant (p < 0.0001). Half the MS-ON eyes had clusters larger than five sectors compared with 13% in MS-no-ON and 2% in controls. Abnormal sectors were distributed diffusely, although the largest cluster was smaller than 15 sectors in two-thirds of MS-ON eyes. Cluster criteria combining amplitude and latency showed an area of 0.96 under the receiver operating characteristic curve, yielding a criterion with 91% sensitivity and 95% specificity. We conclude that the multifocal visual evoked potential provides high sensitivity and specificity in detecting abnormalities in visual function in multiple sclerosis patients.


Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Potenciales Evocados Visuales , Esclerosis Múltiple Crónica Progresiva/complicaciones , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Neuritis Óptica/diagnóstico , Vías Visuales/fisiopatología , Adulto , Estudios de Casos y Controles , Análisis por Conglomerados , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Neuritis Óptica/etiología , Neuritis Óptica/fisiopatología , Estimulación Luminosa , Valor Predictivo de las Pruebas , Curva ROC , Tiempo de Reacción , Recuperación de la Función , Factores de Tiempo , Adulto Joven
10.
Cancer Immun ; 8: 9, 2008 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-18503261

RESUMEN

The cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule on T cells acts to maintain homeostasis by regulating the proliferation of recently activated T cells. Blockade of CTLA-4 by anti-CTLA-4 antibody enhances T cell responses and has elicited significant tumor regression in some cancer patients. Clinical trials are ongoing to investigate the efficacy of anti-CTLA-4 antibody as a cancer therapeutic. Reports from several clinical trials have documented the occurrence of adverse events in patients treated with anti-CTLA-4 antibody which have some similarities with autoimmune conditions and have been termed immune-related adverse events (irAEs). Most irAEs are reversible with corticosteroid therapy. Some investigators suggest that irAEs occur in the same patients who have anti-tumor responses as a result of the anti-CTLA-4 antibody. Immunologic mechanisms to explain why irAEs occur in some patients have not been reported. Here we report that bladder cancer patients treated with anti-CTLA-4 antibody have increased levels of the Th1 cytokine IFN-gamma detected in plasma samples. Although IFN-gamma is a potent anti-tumor and inflammatory cytokine, increased levels of IFN-gamma were not associated with irAEs in our patients. However, in one patient who experienced an irAE consisting of ischemic papillopathy and optic neuritis, we documented high pre-therapy levels of the Th2 cytokine IL-10 which decreased after treatment with anti-CTLA-4 antibody. The decrease in plasma IL-10 concentration coincided with the patient's irAE. We propose that decreased levels of IL-10 after treatment with anti-CTLA-4 therapy may be responsible for irAEs in some patients and needs to be further investigated in larger studies.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antígenos CD/inmunología , Antígenos de Diferenciación/inmunología , Interleucina-10/sangre , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Anticuerpos Monoclonales/uso terapéutico , Antígeno CTLA-4 , Ensayos Clínicos como Asunto , Humanos , Interferón gamma/sangre , Masculino , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/cirugía
11.
Optometry ; 79(2): 90-4, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18215798

RESUMEN

BACKGROUND: Hydroxychloroquine sulfate (Plaquenil; Sanofi-Aventis, Bridgewater, New Jersey) is an antimalarial agent, which is sometimes used for the treatment of certain autoimmune disorders. Its use has been associated with ocular side effects; the most concerning is toxic maculopathy. CASE REPORT: A 71-year-old arthritic white woman requested a second opinion regarding retinal Plaquenil toxicity. The patients history was significant for seronegative rheumatoid arthritis diagnosed 6 years prior. She had taken Plaquenil 400 mg a day for about 5 years but had discontinued the drug 6 months before when bilateral central scotomas were first noted. At the consultation visit, her visual acuities were 20/20 in both eyes. SITA-Standard 10-2 disclosed a dense scotoma with 4 degrees of central sparing in each eye. Fundus examination found retinal pigment epithelium changes bilaterally; no "bulls eye" retinopathy was observed. CONCLUSION: Withdrawal of the medication is the only effective treatment for Plaquenil toxicity and, even then, the toxic effects may progress because of the slow clearance of the drug. Though controversy exists regarding screening recommendations, a baseline ophthalmic examination should be performed on all patients before initiating Plaquenil. If a patient is considered low risk, examinations can be scheduled annually. For high-risk patients, 6-month progress visits are strongly recommended.


Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Hidroxicloroquina/efectos adversos , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Anciano , Antirreumáticos/uso terapéutico , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Hidroxicloroquina/uso terapéutico , Microscopía Acústica , Retina/diagnóstico por imagen , Retina/patología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/fisiopatología , Escotoma/inducido químicamente , Escotoma/diagnóstico , Escotoma/fisiopatología , Agudeza Visual , Pruebas del Campo Visual , Campos Visuales/fisiología
12.
Magn Reson Imaging ; 51: 44-50, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29709464

RESUMEN

PURPOSE: The accurate diagnosis of orbital and anterior visual pathway lesions has clinical significance. We determined whether dynamic contrast-enhanced MRI could differentiate benign from malignant lesions and compared model-independent and model-dependent methods of data analysis. METHODS: We retrospectively reviewed dynamic contrast-enhanced MRI studies of 37 enhancing orbital and anterior visual pathway lesions. The data were processed using model-independent analysis and model-dependent analysis using a 2-compartment pharmacokinetic model. The time-signal intensity curve and semiquantitative parameters from the model-independent method (area under the curve [AUC] after the initial 60, 90, and 120 s; time to peak; maximum signal enhancement ratio; maximum slope of increase; and washout ratio) and the quantitative parameters from the model-dependent method (Ktrans, kep, and ve) were derived for comparison with pathologic diagnoses. RESULTS: The time-signal intensity curves demonstrated different perfusion characteristics and were classified into 4 types. All the lesions that demonstrated curve types 1 and 4 were benign, while type 3 lesions were significantly associated with malignancy (P = 0.001). AUC60, AUC90, AUC120, and kep were significantly lower in benign lesions than in malignant lesions (P = 0.020, 0.018, 0.015, and 0.018, respectively). Receiver operating characteristic analysis indicated that AUC120 yielded the best diagnostic accuracy (area under the curve, 0.80; 95% CI, 0.64-0.96) in differentiating between benign and malignant lesions. CONCLUSIONS: Dynamic contrast-enhanced MRI is useful in evaluating orbital and anterior visual pathway lesions. The model-independent analysis method is equivalent to the model-dependent method in differentiating benign from malignant lesions.


Asunto(s)
Medios de Contraste , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Órbita/diagnóstico por imagen , Vías Visuales/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Encefalopatías/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/diagnóstico por imagen , Neoplasias del Nervio Óptico/diagnóstico por imagen , Neoplasias del Nervio Óptico/secundario , Enfermedades Orbitales/diagnóstico por imagen , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/secundario , Estudios Retrospectivos , Adulto Joven
13.
Invest Ophthalmol Vis Sci ; 48(12): 5798-805, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18055834

RESUMEN

PURPOSE: To investigate the relationship between visual function, measured by standard automated perimetry (SAP), and retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT), in patients with multiple sclerosis (MS). METHODS: SAP and RNFL thickness were measured in patients with MS in 28 eyes with the last optic neuritis (ON) >or=6 months prior (ON group) and 33 eyes without ON history (non-ON group). Abnormal overall or quadrant RNFL thickness was defined by measured values below 5% of the norm. A whole visual field or a sector of the field was classified as abnormal by using cluster criteria on total-deviation plots. Agreement between SAP and OCT results in classifying eyes/sectors was presented as a percentage of observed agreement, along with the AC1 statistic, which corrects for chance agreement. Regression analyses were performed relating several SAP parameters and RNFL thickness in the ON group. RESULTS: ON eyes showed more loss of visual sensitivity (MD, P = 0.02) and more loss of RNFL thickness (P < 0.0001) than did non-ON eyes. SAP and OCT agreed in 86% (AC1 = 0.78) of eyes and 69% (AC1 = 0.38) of sectors in the ON group and 61% (AC1 = 0.33) of eyes and 66% (AC1 = 0.48) of sectors in the non-ON group. Overall RNFL thickness was related to MD (dB) by a simple exponential function (R(2) = 0.48), supporting a linear relationship between these measures when both are expressed on linear scales. Absolute Pearson correlation coefficients for overall RNFL thickness and several SAP parameters ranged from 0.51 to 0.69. CONCLUSIONS: Good agreement between SAP and OCT was found in ON eyes but not in non-ON eyes or in individual sectors in either group. The findings in this study provide further support for the utility of combining structural and functional testing in clinical research on patients with MS, as well as in future neuroprotection trials for which the anterior visual pathways in patients with MS and optic neuritis may be used as a model.


Asunto(s)
Esclerosis Múltiple/fisiopatología , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Trastornos de la Visión/fisiopatología , Campos Visuales/fisiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuritis Óptica/fisiopatología , Tomografía de Coherencia Óptica/métodos , Pruebas del Campo Visual/métodos
14.
Ophthalmology ; 113(2): 333-7, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16406540

RESUMEN

PURPOSE: We report 2 cases of compressive optic neuropathy after use of oxidized regenerated cellulose (ORC) in orbital surgery. To our knowledge, no complications have been reported previously after use of this material in orbital surgery. We also review the complications related to its retention at operative sites outside the orbit and recommend precautions to avoid them. DESIGN: Retrospective interventional case reports. PARTICIPANTS: Two patients with compressive optic neuropathy after use of ORC in orbital surgery. METHODS: Case reports from 2 different clinics and review of the English scientific literature. MAIN OUTCOME MEASURES: Best-corrected visual acuity, extraocular motility, proptosis, and chemosis. RESULTS: One patient underwent orbital exploration and biopsy of an orbital tumor, and the second had repair of an orbital floor fracture. Postoperatively, both presented with chemosis, ophthalmoplegia, and progressive loss of vision. Orbital imaging revealed a retrobulbar soft-tissue density compatible with hematoma. Repeat orbital exploration revealed the soft-tissue mass to be swollen ORC. CONCLUSIONS: Retained intraorbital ORC may cause a compartment syndrome and should be suspected in postoperative patients with orbital symptoms. When ORC is used around the optic nerve, it should be removed after hemostasis is achieved.


Asunto(s)
Celulosa Oxidada/efectos adversos , Cuerpos Extraños en el Ojo/complicaciones , Síndromes de Compresión Nerviosa/etiología , Enfermedades del Nervio Óptico/etiología , Adolescente , Anciano , Exoftalmia/diagnóstico , Exoftalmia/etiología , Cuerpos Extraños en el Ojo/diagnóstico , Cuerpos Extraños en el Ojo/cirugía , Femenino , Hematoma/diagnóstico , Hematoma/etiología , Hematoma/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Síndromes de Compresión Nerviosa/diagnóstico , Síndromes de Compresión Nerviosa/cirugía , Oftalmoplejía/diagnóstico , Oftalmoplejía/etiología , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/cirugía , Fracturas Orbitales/cirugía , Neoplasias Orbitales/cirugía , Estudios Retrospectivos , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/etiología , Agudeza Visual
15.
Surv Ophthalmol ; 50(6): 588-97, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16263371

RESUMEN

A 50-year-old female presented with progressive painless vision loss in the left eye and was subsequently diagnosed to have a pituitary macroadenoma, consistent with a prolactinoma, which was compressing the chiasm primarily on the left and involving the left cavernous sinus. She was treated with oral bromocriptine, resulting in marked shrinkage of the tumor and significant visual field recovery. Subsequently, she again began noting progressive vision loss in both eyes and was initially thought to have pituitary tumor regrowth. Repeat brain MRI, however, showed chiasmal prolapse with inferior tethering into an empty sella. Surgical fat padding to reposition the chiasm resulted in visual improvement with a different visual field pattern in the left eye. The clinical manifestations and etiopathogenesis of the empty sella syndrome are discussed.


Asunto(s)
Síndrome de Silla Turca Vacía/etiología , Quiasma Óptico/patología , Enfermedades del Nervio Óptico/etiología , Neoplasias Hipofisarias/complicaciones , Prolactinoma/complicaciones , Trastornos de la Visión/etiología , Tejido Adiposo/trasplante , Bromocriptina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Síndrome de Silla Turca Vacía/diagnóstico , Síndrome de Silla Turca Vacía/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/cirugía , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/diagnóstico , Prolactinoma/tratamiento farmacológico , Prolapso , Trastornos de la Visión/fisiopatología , Pruebas del Campo Visual , Campos Visuales/fisiología
16.
J Telemed Telecare ; 11(8): 391-6, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16356312

RESUMEN

Tele-ophthalmology has been employed mainly for patients in under-served rural areas in need of specialty care, but other applications such as telementoring have also been used. In certain populations, cost containment is a significant issue and telemedicine is a solution. Tele-ophthalmology can be performed in realtime, by store-and-forward mode, or by hybrid techniques. After appropriate modification, a range of peripherals may be used for tele-ophthalmology, including the direct ophthalmoscope, indirect ophthalmoscope, slit lamp or retinal camera. Tele-ophthalmology applications include: detecting, screening and diagnosing diabetic retinopathy; anterior segment imaging; glaucoma screening; low vision consultation; telementoring. Tele-ophthalmology shows great promise for improving patient care and increasing access to specialty care not available in under-served areas. In developing countries tele-ophthalmology may be a cost-effective method by which richer countries can assist them.


Asunto(s)
Retinopatía Diabética/diagnóstico , Glaucoma/diagnóstico , Telemedicina/métodos , Selección Visual/métodos , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Oftalmoscopía , Telemedicina/instrumentación , Selección Visual/instrumentación
17.
Neuroimaging Clin N Am ; 25(3): 327-65, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26208413

RESUMEN

Ophthalmic ultrasound is an invaluable tool that provides quick and noninvasive evaluation of the eye and the orbit. It not only allows the clinicians to view structures that may not be visible with routine ophthalmic equipment or neuroimaging techniques but also provides unique diagnostic information in various ophthalmic conditions. In this article, the basic principles of ophthalmic ultrasound and examination techniques are discussed. Its clinical application is illustrated through a variety of ocular pathologic abnormalities (eg, narrow angles, ciliary body tumor, detached retina, choroidal melanoma, and papilledema).


Asunto(s)
Oftalmopatías/diagnóstico por imagen , Microscopía Acústica/métodos , Neuroimagen/métodos , Enfermedades Orbitales/diagnóstico por imagen , Ultrasonografía/métodos , Humanos , Aumento de la Imagen/métodos
18.
Neuroimaging Clin N Am ; 25(3): 367-82, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26208414

RESUMEN

Optical coherence tomography is an imaging technique using low coherence light sources to produce high-resolution cross-sectional images. This article reviews pertinent anatomy and various pathologies causing optic atrophy (eg, compressive, infiltrating, demyelinating) versus optic nerve swelling (from increased intracranial pressure known as papilledema or other optic nerve intrinsic pathologies). On optical coherence tomography, optic atrophy is often associated with reduced average retinal nerve fiber layer thickness, whereas optic nerve swelling is usually associated with increased average retinal nerve fiber layer thickness.


Asunto(s)
Glaucoma/patología , Neuroimagen/métodos , Enfermedades del Nervio Óptico/patología , Nervio Óptico/patología , Enfermedades de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Humanos , Aumento de la Imagen/métodos
19.
Invest Ophthalmol Vis Sci ; 45(10): 3827-37, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15452095

RESUMEN

PURPOSE: To determine whether anterior ischemic optic neuropathy and compressive optic neuropathy in humans alter the photopic flash ERG and to investigate the cellular origins of the waves that are affected by pharmacologic agents in primates. METHODS: Photopic flash ERGs were recorded differentially, with DTL electrodes, between the two eyes of 22 patients with diagnosed optic neuropathy (n = 17, anterior ischemic optic neuropathy [AION]; n = 5, compressive optic neuropathy) and 25 age-matched control subjects and in 17 eyes of 13 monkeys (Macaca mulatta). The stimulus consisted of brief (<5 ms) red (lambda(max) = 660 nm) Ganzfeld flashes (energy range, 0.5-2.0 log td-s) delivered on a rod-saturating blue background of 3.7 log sc td (lambda(max) = 460 nm). An eye of the patient with ischemic changes at the disc was classified as symptomatic if it showed visual field defects with a mean deviation (MD) of P < 2%. Recordings in macaque monkeys were made before and after inner retinal blockade with tetrodotoxin (TTX) (1.2-2.1 microM; n = 7), TTX+N-methyl-d-aspartate (NMDA; 1.4-6.4 mM; n = 7), and cis-2, 3 piperidine dicarboxylic acid (PDA; 3.3-3.8 mM; n = 3). RESULTS: The PhNR amplitude was significantly reduced in both symptomatic (P = 3.4 x 10(-8)) and asymptomatic (P = 0.036) eyes of patients with AION or compressive optic neuropathy (P = 0.0054) compared with control subjects. The PhNR amplitude in the symptomatic eye showed a moderate correlation with field defects (P < 0.05) similar to previous findings in open-angle glaucoma. The a-wave also was reduced significantly in the symptomatic eye (P = 0.0002) of patients with AION. The i-wave, a positive wave on the trailing edge of the b-wave peaking around 50 ms, became more prominent in eyes in which the PhNR was significantly reduced. In monkeys, the PhNR was eliminated by TTX. The a-wave at the peak and later times was reduced by TTX, further reduced by NMDA, and eliminated after PDA in response to the red stimuli. PDA also eliminated the i-wave. CONCLUSIONS: PhNR amplitude is significantly reduced in eyes with open-angle glaucoma, AION, and compressive optic neuropathy. Experiments in primates indicate that this reduction reflects loss of a spike-driven contribution to the photopic ERG. There also are small spike-driven contributions to the a-wave elicited by full-field red stimuli. The i-wave, which becomes more prominent when the PhNR is reduced, has origins in the off-pathway distal to the ganglion cells.


Asunto(s)
Glaucoma de Ángulo Abierto/fisiopatología , N-Metilaspartato/farmacología , Enfermedades del Nervio Óptico/fisiopatología , Ácidos Pipecólicos/farmacología , Retina/efectos de los fármacos , Retina/fisiopatología , Tetrodotoxina/farmacología , Adulto , Anciano , Animales , Electrorretinografía , Femenino , Humanos , Luz , Macaca mulatta , Masculino , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/fisiopatología , Neuropatía Óptica Isquémica/fisiopatología , Estimulación Luminosa
20.
J Clin Exp Ophthalmol ; 4(6): 307, 2013 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24672741

RESUMEN

BACKGROUND: The presence of autoantibodies (AAbs) is the primary serological indicator of autoimmunity. Cancer-associated retinopathy (CAR) is associated with AAbs and different types of cancer. The goal of the study was to examine the profile of serum autoantibodies in women with gynecological cancers with and without paraneoplastic visual manifestation. METHODS: Retrospective studies of a cohort of 46 women with symptoms of CAR and gynecological tumors, including endometrial, cervical, ovarian, and fallopian tubes, 111 women with similar tumors without symptoms of CAR, and 60 age-matched healthy controls. Presence of serum AAbs and the identity of targeted antigens were performed by western blotting and their significance was evaluated using an Fisher's exact test. RESULTS: The patients with gynecological CAR had the highest proportion of seropositivity (80%), followed by patients with gynecological cancers without CAR (61%) and healthy controls (58%). Differences in recognition frequencies were found for 17 antigens and 5 retinal antigens were frequently targeted: enolase, aldolase C, carbonic anhydrase II, recoverin and GAPDH. The occurrence of anti-glycolytic enzymes was 2-3 times more frequent in CAR and cancer patients than healthy controls. Anti-recoverin AAbs were prevalent in endometrial CAR. Anti-CAII antibodies were not significantly different between groups of women. In this cohort, cancer was diagnosed before the onset of retinopathy with latency from 2 months to 30 years. The discovery of the ovarian and endometrial cancers and manifestation of visual problems often coincided but Fallopian tube carcinoma was found after visual onset. CONCLUSION: New retinal targets were identified for gynecological CAR. Each gynecological-CAR has its own autoantibody profile different from non-CAR profile, implying that a complex autoantibody signature may be more predictable for diagnosis than a singular AAb. Specific anti-retinal AAbs were most prevalent in women with CAR but their profiles were not fully distinguished from cancer controls.

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