Objective Diplopia Outcomes for Patients Treated With Teprotumumab for Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease (TED) is a condition caused by inflammatory damage to the periocular tissue that often leads to double vision. Teprotumumab is an insulin-like growth factor 1 receptor antibody that was FDA approved for the management of TED in 2020, although much is yet to be elucidated regarding its effects on diplopia outcomes among patients with TED. Diplopia is a significant and life-altering effect of TED. Previous studies have reported the effect of teprotumumab on double vision subjectively using the Gorman diplopia score. However, there is a gap in the literature addressing the effect of teprotumumab treatment on objective ocular alignment measures. The purpose of our study was to address this gap. METHODS: We performed a retrospective review of patients who were diagnosed with TED, presented with diplopia, and treated with teprotumumab in a single-center academic ophthalmology practice. The primary outcome was change in ocular alignment in primary gaze position at 6 months (completion of teprotumumab treatment). Secondary outcomes included change in ocular alignment in other gaze positions, proptosis, eyelid position, and clinical activity score (CAS) at 6 months compared with baseline. To determine what factors may predict ocular alignment response to teprotumumab, we analyzed baseline characteristics among 3 groups, divided based on whether ocular alignment was worsened, stable, or improved at 6 months. RESULTS: Seventeen patients met inclusion criteria, 3 (18%) worsened, 10 (59%) were stable, and 4 (24%) improved. CAS ( P = 0.02) was significantly different among the groups and was higher in those who worsened and those who improved compared with those who remained stable. Right gaze horizontal prism deviation ( P = 0.01) and left gaze horizontal prism deviation ( P = 0.03) were significantly different among the groups, with a greater degree of left gaze horizontal prism deviation in the worse group than the stable group ( P = 0.04). CONCLUSIONS: Our study demonstrated that most patients remained stable after teprotumumab treatment regarding ocular alignment in primary gaze and the number of patients who improved was slightly higher than the number of patients who worsened after teprotumumab treatment. There are some baseline measures, such as CAS and right and left gaze horizontal prism deviation that can help better predict how a patient will respond to teprotumumab treatment. Our results can better inform physicians of how to counsel patients with TED when considering teprotumumab therapy.

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease: Follow-Up Outcomes in Three Clinical Trials.

Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves' Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responses from the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose.

Desarrollo de miastenia gravis tras administración de toxina botulínica en el síndrome de dolor miofascial / Development of myasthenia gravis after botulinum toxin management in myofascial pain syndrome

El síndrome de dolor miofascial (SDM) es una patología muscular dolorosa que se define como dolor local o referido asociado a la presencia de nódulos palpables hipersensibles en el trayecto de ese músculo y constituye una patología frecuente en las consultas de dolor crónico.La toxina botulínica es una exotoxina producida por el Clostridium botulinum, cuyos serotipos A, B y F tienen utilidad clínica (fundamentalmente tipo A- Botox®, Dysport®). Se trata de una de las neurotoxinas más potentes que existen. Se utiliza como uso compasivo en el tratamiento del síndrome de dolor miofascial. El efecto beneficioso analgésico del uso de la toxina se origina de reducir la hiperactividad muscular pero estudios recientes sugieren que esta neurotoxina puede tener efectos analgésicos directos diferentes de sus acciones neuromusculares. Su uso no está exento de riesgos. Los efectos adversos se relacionan con la migración de la toxina y son en general leves o moderados y pasajeros. Se han descrito casos de debilidad muscular prolongada e incluso cuadros de miastenia gravis, síndrome de Eaton Lambert desencadenados por el uso de la toxina.Presentamos el caso clínico de un varón afecto de síndrome de dolor miofascial del cuadrado lumbar y psoas tratado con infiltraciones con toxina botulínica. Tras la mejoría del cuadro clínico muscular se desarrolla diplopía y ptosis palpebral reiterante, siendo diagnosticado de miastenia gravis. Revisamos la etiopatogenia del síndrome de dolor miofascial y de la miastenia gravis, así como el uso de la toxina botulínica y sus relaciones entre ellos Concluimos que es necesaria una anamnesis detallada previa a la utilización de toxina botulínica sobre patología muscular o signos de debilidad muscula (AU)

Myofascial pain syndrome is a painful muscle condition which is defined as local or referred pain associated with hypersensitive palpable nodules in the way of that muscle and is a frequent pathology in consultations on chronic pain.Botulinum toxin is an exotoxin produced by Clostridium botulinum, of which serogroups A, B and F have clinical utility (mainly type A- Botox®, Dysport®). This is one of the most potent neurotoxins and is administered compassionatelly in the treatment of myofascial pain syndrome. The toxin has a beneficial analgesic effect by reducing muscle hyperactivity but recent studies suggest that this neurotoxin may also induce analgesia by non-neuromuscular actions. Its use is not without risks. Adverse effects are related to the migration of the toxin and are usually mild or moderate and transient. There have been reports of prolonged muscle weakness and diseases like myasthenia gravis or Lambert Eaton syndrome triggered by the use of the toxin.We report a case of a male patient with myofascial pain syndrome whose psoas and quadratus muscles were treated with injections of botulinum toxin. Following the improvement in clinical muscle situation, repetitive diplopia and ptosis developed and the patient was diagnosed of myasthenia gravis.We review the pathogenesis of myofascial pain syndrome and myasthenia gravis and the use of botulinum toxin and relationships between them.We conclude that a detailed history is required prior to the use of botulinum toxin on patients with muscle pathology or signs of muscle weakness (AU)

Botox® after Botox® - a new approach to treat diplopia secondary to cosmetic botulinic toxin use: case reports / Botox® após Botox® - uma nova abordagem para tratamento de diplopia secundária ao uso cosmético de toxina botulínica: relatos de casos

A new technique for the treatment of diplopia secondary to cosmetic botulinum toxin A use is described. In this interventional case reports, two consecutive patients who developed diplopia after periocular cosmetic use of botulinum toxin A were treated with intramuscular botulinum toxin A injection into the antagonist extraocular muscle. Diplopia resolved in both patients in less than 1 week with no side effects or complications. In conclusion, the injection of intramuscular botulinum toxin A is an encouraging option for treatment of diplopia secondary to botulinum toxin A use for facial lifting.

Uma nova técnica para tratamento de diplopia secundária ao uso estético da toxina botulínica A é descrito. Nestes relatos de casos, dois pacientes consecutivos que desenvolveram diplopia após uso cosmético de toxina botulínica A periocular foram tratados com injeção de toxina botulínica A no músculo extraocular antagonista. A diplopia melhorou em menos de uma semana nos dois pacientes, sem efeitos colaterais. Consideramos o uso de injeção intramuscular de toxina botulínica A como uma possível opção para o tratamento da diplopia secundária ao uso da toxina botulínica A para rejuvenescimento facial.

Osteoma frontoetmoidal con extensión intraorbitaria. A propósito de un caso / Frontoethmoidal osteoma with orbital extension. A case report

CASO CLÍNICO: Presentamos el caso de un osteoma frontoetmoidal derecho con invasión intraorbitaria en un varón de 43 años que comenzó como un cuadro de dolor retroocular con proptosis, inflamación peripalpebral y diplopía binocular por limitación del recorrido muscular. Se realizó cirugía abierta mediante abordaje subcraneal anterior, con extirpación de varios fragmentos de osteoma, cuyo análisis histológico confirmó el diagnóstico. DISCUSIÓN: Los osteomas son tumores benignos formadores de hueso de crecimiento lento. Habitualmente son asintomáticos, hasta que producen complicaciones por efecto masa en el cerebro o en la órbita, o a nivel local, hasta que obstruyen el drenaje del seno donde asientan, generando mucoceles

CASE REPORT: A case is presented of a right frontoethmoidal osteoma with intraorbital invasion in a 43-year-old male, who was seen in the clinic with a proptosis, retro-orbital pain, peri-palpebral inflammation, and binocular diplopia due to muscular route limitation. Open surgery was performed using a subcranial approach, with removal of several fragments of osteoma. Histological analysis confirmed the diagnosis. DISCUSSION: Osteomas are benign bone-forming tumours with slow growth. They are usually asymptomatic until mass effect complications occur in the brain or in the orbit, or locally, generating mucoceles due to sinus drainage obstruction

Aplicaciones clínicas de la toxina botulínica en el estrabismo: estudio de las inyecciones realizadas durante un año en un hospital general / Botulinum toxin uses in strabismus: A review of the injections performed during one year in a general hospital

OBJETIVO: Analizar las indicaciones, dosis y eficacia de las inyecciones de toxina botulínica A en el departamento de Estrabología. MÉTODO: En este estudio prospectivo, 28 pacientes diagnosticados de estrabismo fueron tratados con toxina botulínica. Se recopilaron los pacientes tratados en 2013 en el Hospital Rey Juan Carlos (Móstoles) para estudiar las indicaciones, la dosis empleada, y se analizaron los resultados de la última revisión, tanto en niños como en adultos, con un seguimiento mínimo de 14 meses. RESULTADOS: Se recogieron datos de 11 niños, 6 mujeres (54,5%), y 17 adultos, 11 varones (64%). La edad media fue 4,42 ± 3,48 años y 58,71 ± 18,07 años en niños y adultos respectivamente. En ambos grupos la mayoría de los casos eran endotropias (81,8% en niños y 47,1% en adultos), aunque el grupo de adultos presentaba enfermedades más heterogéneas incluyendo 4 pacientes con exotropía (26,5%), 4 con hipertropía (26,5%) y uno con nistagmo aislado (5,9%). La media de inyecciones en niños fue de 1,45 ± 0,93, aunque el 72,7% recibieron una única inyección; en el grupo de adultos la media de inyecciones fue de 3,27 ± 1,41. Se encontró una diferencia estadísticamente significativa en la comparación de tropia y foria prepostinyección en niños y adultos (p < 0,05). En ambos grupos hubo una mejoría significativa en el tortícolis postinyección comparado con el previo (p < 0,05). En 4 niños pudimos detectar una mejoría en la estereoagudeza. Dos niños (18,2%) y 5 adultos (29,4%) precisaron intervención quirúrgica posterior. Ocho adultos (49,1%) presentaban diplopia en posición primaria de la mirada, que se resolvió en 6 casos con inyecciones de toxina, pero 2 necesitaron cirugía para la corrección de la diplopia. Las diferencias entre tropia y foria pre- y postintervención fueron estadísticamente significativas (p < 0,05), así como las diferencias entre el tortícolis pre- y postinyección. En 4 casos se pudo detectar mejoría en la estereoagudeza. CONCLUSIONES: La toxina botulínica es un fármaco muy útil en el estrabismo, con mejores resultados sensoriales y motores en los niños, pero eficaz como tratamiento sintomático en algunos casos de estrabismo en adultos

OBJECTIVE: To analyse the indications, dosage and efficacy of botulinum toxin A injection performed in patients in a Strabismus Department. METHODS: In this prospective study, botulinum toxin A was injected into 28 patients diagnosed with strabismus. Data was obtained from the records of patients that were evaluated during 2013 in the Strabismus Unit of Rey Juan Carlos Hospital (Móstoles, Madrid, Spain) in order to assess the indications and dosage of botulinum toxin A use in strabismus, as well as its clinical effect and differences in paediatric and adult patients. The outcomes in the last visit, at least 14 months after the injections, were analysed. RESULTS: An analysis was performed on the data from 11 children, 6 females (54.5%), and 17 adults, 11 males (64%). The mean age was 4.42 ± 3.48 years and 58.71 ± 18.07 years in the children and adult groups, respectively. The majority of cases in both groups were esotropia (81.8% in children and 47.1% in adults). However the pathologies in the adult group were quite heterogeneous, including 4 patients with exotropia (26.5%), 4 with hypertropia (26.5%), and one with isolated nystagmus (5.9%). The mean number of the botulinum toxin injections in children was 1.45 ± 0.93, although 72.7% received a single injection. In the adult group, the mean number of injections was 3.27 ± 1.41. There was a statistically significant difference between pre- and post-injection in the tropia and phoria measurements in children and adults group (P<.05). In both groups there was a statistically significant improvement in post-injection torticollis when compared with the pre-injection measurement (P<.05). An improvement in the stereoacuity could be detected in 4 children. Two children (18.2%) and 5 adults (29.4%) required subsequent surgical intervention. Eight adult patients (49.1%) complained of diplopia in the primary position, which was resolved in 6 cases with toxin injection, whereas 2 needed surgery for diplopia correction. CONCLUSIONS: Botulinum toxin is a very useful tool in the management of strabismus, obtaining better sensory and motor results in children, but it is also effective as a symptomatic treatment in some types of strabismus in adults

Evaluación de la efectividad del tratamiento con glucocorticoides intravenosos en la oftalmopatía de Graves / Obesity: etiologic and pathophysiological analysis

Objetivo: Evaluar la efectividad del protocolo de tratamiento intermitente con glucocorticoides a altas dosis por vía intravenosa (i.v.) en la oftalmopatía de Graves (OG) moderada-grave del Hospital Reina Sofía. Material y métodos Se incluyeron los pacientes con OG tratados con glucocorticoides i.v. en nuestro servicio desde agosto de 2007 a agosto de 2011. Se administró prednisolona i.v. en dosis de 7,5mg/kg/d 2d alternos durante 6 semanas alternas y mitad de la dosis durante 6 semanas más. Resultados Analizamos 18 pacientes (83,3% mujeres) con una edad media de 43±11 años. Cuatro eran fumadores, 5 habían dejado el hábito y el resto nunca habían fumado. El 66,7% presentaban hipertiroidismo por enfermedad de Graves, de los cuales el 41,6% habían recibido radioyodo. La respuesta al tratamiento fue buena en el 72,2%, parcial en 11,1% y mala en 16,7%. En 5 aparecieron efectos secundarios leves. Antes del tratamiento el 83,3% presentaron diplopía, el 33,3% retracción palpebral, el 72,2% dolor ocular y el 44,4% exoftalmos. Después del tratamiento solo el 33,3% continuaron con diplopía (p=0,004), el 5,6% con retracción palpebral (p=0,063), el 16,7% con dolor ocular (p=0,002) y el 11,1% con exoftalmos (p=0,031). El 22,2% precisaron radioterapia. La respuesta al tratamiento no se asoció a la enfermedad de base (p=0,866) al haber recibido radioyodo previo como tratamiento del hipertiroidismo (p=0,447) o al ser fumador (p=0,368).Conclusiones El tratamiento con glucocorticoides i.v. en la oftalmopatía tiroidea reduce significativamente la diplopía, el dolor ocular y el exoftalmos. Los efectos secundarios son leves y poco frecuentes. La respuesta al tratamiento es independiente de la enfermedad de base, de haber recibido radioyodo y de ser fumador (AU)

Objective: To assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves’ ophthalmopathy (GO).Materials and methods: Patients with GO treated with IV GCs from August 2007 to August 2011at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulseprednisol one (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks. Results: Eighteen patients (mean age, 43+/-11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves’ disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment,83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P = .004), 5.6% eyelid retraction (P = .063), 16.7% eye pain(P = .002), and 11.1% exophthalmos (P = .031). Response to treatment was not related to the underlying disease (P = .866), prior radioiodine treatment (P = .447), or smoking status (P = .368).Conclusions: Intravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status (AU)

Otomastoiditis aguda y trombosis del seno lateral. Presentación de un caso

La trombosis del seno lateral (TSL) es una rara complicación de la otitis media aguda hoy en día, pues con los nuevos agentes antimicrobianos se ha reducido mucho la incidencia de las otitis media y la mastoiditis disminuyendo por tanto sus complicaciones intracraneales. Las imágenes de Resonancia magnética y de angioresonancia son las técnicas de elección para el diagnóstico y el seguimiento de las trombosis venosas cerebrales. Presentamos un caso de TSL como una complicación intracraneal de una otitis media y mastoiditis en una paciente de 7 años de edad que estaba siendo tratada previamente durante 7 días con Azitromicina por una otitis media aguda derecha diagnosticada en su centro de salud. Después del tratamiento intravenoso con antibióticos, anticoagulantes, dexametasona y drenaje del oído medio, la infección curó sin complicaciones (AU)