Afectación iatrogénica de la motilidad ocular por fármacos antitumorales inhibidores de los puntos de control / Iatrogenic impairment of ocular motility by immune checkpoint inhibitors

Se encontraron 4 revisiones sistemáticas que incluían este tipo de iatrogenia ocular, así como numerosos reportes de casos aislados. Los efectos adversos reportados comprenden: paresias oculomotoras, neuropatía óptica, atrofia óptica, síndromes miasteniformes, pseudo-orbitopatía tiroidea, síndrome del ápex orbitario e hipofisitis. La mayoría se manejaron sin interrupción o con interrupción parcial del tratamiento oncológico. Se requirieron tratamientos sistémicos agresivos para el manejo adecuado de la iatrogenia ocular.Es imprescindible que el oftalmólogo se familiarice con los nuevos tratamientos oncológicos ICI, capaces de provocar iatrogenia sobre la motilidad ocular grave e incapacitante para el paciente. La comunicación de efectos adversos con los tratamientos empleados puede ayudar al manejo más adecuado de estos pacientes. La investigación debe ir orientada al diagnóstico diferencial complejo y a optimizar las decisiones sobre los tratamientos oncológicos. (AU)

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile.We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events.It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments. (AU)

Iatrogenic affectation of ocular motility by immune checkpoint inhibitors.

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile. We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events. It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments.

Lesión permanente de las capas internas de la retina en una paciente con migraña: un caso diferente de maculopatía paracentral aguda media / Permanent damage of the inner retinal layers in a patient with migraine: A different case of paracentral acute middle maculopathy

Presentamos el caso de una paciente mujer de 20 años que consultó por un escotoma paracentral en su ojo izquierdo que no había desaparecido después de una crisis de migraña 2 días antes. La exploración realizada evidenció la presencia de 2 áreas de palidez retiniana sugestivas de isquemia aguda. Tras descartar varias causas de isquemia retiniana aguda, se llegó al diagnóstico de un síndrome vasoespástico retiniano. Un año después, la paciente presenta una atrofia de las capas internas de la retina afectada y sufre un escotoma paracentral crónico en su ojo izquierdo. Los vasoespasmos retinianos pueden provocar un daño irreversible y crónico debido a la destrucción tisular por la isquemia. Este inusual caso describe una lesión permanente secundaria a un vasoespasmo arterial tras una crisis de migraña. El hallazgo de lesiones retinianas características y la historia de migraña hacen el diagnóstico compatible con un episodio de maculopatía paracentral aguda media (AU)

We report the case of a 20-year-old patient who presented a paracentral scotoma in her left eye that had not disappeared after a migraine attack 2 days before. Ocular examination showed 2 pale paracentral areas suggesting an acute ischemia insult. Several causes of retinal ischemia were ruled out and the patient was diagnosed with secondary retinal vasospasm. One year later, the patient suffers an atrophy of the inner layers of the affected retina and has a paracentral chronic scotoma in her left eye. Retinal vasospasms can result in irreversible lesions and chronic symptoms due to ischemia and cell destruction. This unusual case reports a permanent damage due to retinal vasospasm secondary to migraine attack. The finding of typical lesions and the history of migraine could be compatible with the diagnosis of paracentral acute middle maculopathy (AU)

Permanent damage of the inner retinal layers in a patient with migraine: a different case of paracentral acute middle maculopathy.

We report the case of a 20-year-old patient who presented a paracentral scotoma in her left eye that had not disappeared after a migraine attack two days before. Ocular examination showed two pale paracentral areas suggesting an acute ischemia insult. Several causes of retinal ischemia were ruled out and the patient was diagnosed with secondary retinal vasospasm. One year later, the patient suffers an atrophy of the inner layers of the affected retina and has a paracentral chronic scotoma in her left eye. Retinal vasospasms can result in irreversible lesions and chronic symptoms due to ischemia and cell destruction. This unusual case reports a permanent damage due to retinal vasospasm secondary to migraine attack. The finding of typical lesions and the history of migraine could be compatible with the diagnosis of paracentral acute middle maculopathy (PAMM).

Oscilaciones oculares con implicaciones neurológicas en la edad infantil / Eye oscilations with neurological implications in pediatric age

Introducción Oscilaciones oculares, tanto nistágmicas como no nistágmicas, pueden ocurrir desde el nacimiento. La mayoría corresponden a nistagmos infantiles que aparecen en los seis primeros meses de vida, donde se incluyen el nistagmo motor idiopático, sensorial, latente o latente manifiesto. Aquellas asociadas con enfermedades o síndromes neurológicos corresponden aproximadamente al 33%, siendo importante su identificación y correcta valoración dadas las potenciales complicaciones tanto visuales como vitales. Material y métodos Hemos realizado una revisión sistemática de la literatura sobre los mecanismos de control supranuclear de la mirada y de las principales oscilaciones oculares con posibles implicaciones neurológicas, ambas en la edad infantil. Pretendemos con ello valorar si existen asociaciones clínico-anatómicas ya establecidas, y plantear un protocolo sobre los estudios complementarios a realizar en estos casos. Resultados Existen todavía vías anatómicas implicadas en el control supranuclear de la mirada que no están totalmente esclarecidas y entendidas. Además, salvo en el caso de los nistagmos en seesaw y en upbeat, no hemos encontrado explicaciones anatómicas sobre la patogénesis de los mismos. Sí que queda clara la necesidad de realizar exploraciones físicas neurooftalmológicas completas y la petición de pruebas complementarias en los niños que presenten oscilaciones oculares con características neurológicas. Conclusiones El control supranuclear de la mirada sigue una compleja red neurológica que aún necesita ser estudiada en mayor profundidad. Con una mejor definición de la misma podríamos intentar entender por qué las oscilaciones oculares que estudiamos tienen esas formas de presentación específicas. En cuanto a las peticiones complementarias, es prácticamente constante la solicitud de pruebas de neuroimagen, realizando las demás según el caso concreto ante el que nos econtremos. (AU)

Introduction Eye oscillations, both nystagmic and non-nystagmic, can occur from birth. Most correspond to infantile nystagmus that appears in the first six months of life, which include idiopathic, sensory, latent, or overt latent motor nystagmus. Those associated with neurological diseases or syndromes correspond to approximately 33%, their identification and correct evaluation being important given the potential visual and vital complications. Material and methods We made a systematic review of the literature on supranuclear gaze control mechanisms and the main ocular oscillations with possible neurological implications, both in childhood. With this, we intend to assess if there are already established clinical-anatomical associations, and to propose a protocol on the complementary studies to be carried out in these cases. Results There are still anatomical pathways involved in supranuclear gaze control that are not fully clarified and understood. Besides, except in the case of nystagmus in seesaw and upbeat, we did not find anatomical explanations for their pathogenesis. The need for complete neuro-ophthalmological physical examinations and the request for additional tests in children who present ocular oscillations with neurological characteristics are clear. Conclusions Supranuclear gaze control follows a complex neurological network that still needs to be studied better. With a better definition thereof we could try to understand why the ocular oscillations that we studied have these specific forms of presentation. As for the complementary requests, the request for neuroimaging tests is practically constant, making the others according to the specific case before which we find ourselves. (AU)

Paquimeningitis relacionada con IgG4 y la visión. Reporte de caso / Ophthalmological manifestations of IgG4-related pachymeningitis. A case repor

Introducción: la inmunoglobulina G4 es un subtipo de inmunoglobulina G que corresponde a menos del 5% del total de inmunoglo-bulinas. Niveles elevados de esta molécula se han asociado con el desarrollo de diferentes patologías. Método: presentación de caso clínico. Resultados: se presenta el caso de una mujer de 51 años que consultó por disminución de agudeza visual, escotoma central en ojo izquierdo y edema de papila bilateral. Se encontraron signos compatibles con paquimeningitis en la resonancia nuclear magnética. También presentó aumento de presión de apertura en la punción lumbar. En el estudio de laboratorio se observó un aumento en los niveles plasmáticos de IgG4, lo cual llevó al diagnóstico de paquimeningitis relacionada con IgG4. La paciente fue tratada con corticoides y azatioprina, con excelente evolución posterior al normalizar agudeza visual y campos visuales. Conclusión: en este artículo se describen tres elementos importantes a considerar en estos pacientes: pérdida de visión, edema de discos ópticos y cambios en campo visual.

Introduction: G4 immunoglobulin is 5% of total immunoglobulins in plasma. Elevated levels of this protein are associated with several diseases. Methods: clinical case report. Results: we report a case of a 51-year-old woman who presented with loss of vision, a central scotoma over her left eye and bilateral optic disc edema. She had findings compatible with pachymeningitis based on magnetic resonance imaging. She also exhibited an increased opening pressure in lumbar puncture. In the laboratory workup, we found a two-fold increase in IgG4 levels, which led to a diagnosis of pachymeningitis related to IgG4. The patient was treated accordingly with corticosteroids and azathioprine. The patient experienced excellent progression with complete recovery of her visual acuity and normalization of the visual fields. Conclusion: there is three elements to consider in these patients: vision loss, optic disc edema and visual field changes.

[New mutation in a young woman diagnosed with Niemann-Pick disease type C]. / Nueva mutación descrita en una mujer joven con esplenomegalia, diagnosticada de enfermedad de Niemann-Pick tipo C.

BACKGROUND AND OBJETIVE: To describe a new molecular variant of Niemann-Pick disease type C (NPC) in a 27 year-old patient with splenomegaly and abolition of osteotendinous reflexes. MATERIAL AND METHODS: NPC1 is the main gene with described mutation in NPC disease. Here we report a case with a new mutation, p.N916S, not described before in a patient diagnosed with NPC. RESULTS: p.N916S was described as a cause of NPC disease by predictive programmes Mutation Master, PolyPhen2 and SIFT. CONCLUSIONS: p.N916S is a new mutation detected as a cause of NPC disease in a patient without severe neurological symptoms.

Smooth pursuit eye movements and schizophrenia: literature review.

OBJECTIVE: To review the scientific literature about the relationship between impairment on smooth pursuit eye movements and schizophrenia. METHODS: Narrative review that includes historical articles, reports about basic and clinical investigation, systematic reviews, and meta-analysis on the topic. RESULTS: Up to 80% of schizophrenic patients have impairment of smooth pursuit eye movements. Despite the diversity of test protocols, 65% of patients and controls are correctly classified by their overall performance during this pursuit. The smooth pursuit eye movements depend on the ability to anticipate the target's velocity and the visual feedback, as well as on learning and attention. The neuroanatomy implicated in smooth pursuit overlaps to some extent with certain frontal cortex zones associated with some clinical and neuropsychological characteristics of the schizophrenia, therefore some specific components of smooth pursuit anomalies could serve as biomarkers of the disease. Due to their sedative effect, antipsychotics have a deleterious effect on smooth pursuit eye movements, thus these movements cannot be used to evaluate the efficacy of the currently available treatments. CONCLUSION: Standardized evaluation of smooth pursuit eye movements on schizophrenia will allow to use specific aspects of that pursuit as biomarkers for the study of its genetics, psychopathology, or neuropsychology.

Confiabilidad de la campimetría manual por confrontación para detectar defectos de campos visuales en patologías neurológicas / Reliability of confrontation testing of visual fields in neurological diseases

Introduction: Different methods of assessing visual field by confrontation (VFC) with the Goldmann Perimetry (GP) are compared. Method: 52 consecutive patients evaluated in Neuropthalmology Department that met inclusion criteria. Seven tests of VFC and GP are performed on each patient. Sensitivity, specificity and degree of association of each test confrontation regarding Goldmann Perimetry is evaluated. Results: The tests were the most sensitive tests comparing fingers (58%) and compared red (55%) Color object. Greater specificity tests were counting fingers (95%), finger movement in a fixed position of the hand in different quadrants (95%), finger movement from the periphery to the center of the quadrants (93%) and test moving red pin of 5 mm (93%). The two most sensitive tests had low specificity. Conclusions: The VFC is performed routinely in all neuroopthalmology patients. Tests are of limited use for screening visual pathway pathology because of its low sensitivity but the detected alterations are sufficiently specific. The most useful tests were dynamic (moving from the periphery to the center finger or a red pin). To confirm the diagnosis and monitoring is needed as objective evidence of Goldmann Perimetry.

Introducción: Se comparan distintos métodos de evaluación de campo visual por confrontación (CVC) con la Campimetría de Goldmann (CG) en pacientes derivados al Servicio de Neuroftalmología del Instituto de Neurocirugía. Método: En cincuenta y dos pacientes consecutivos que cumplen criterios de inclusión, se realizan siete pruebas de CVC y CG en cada paciente. Se evalúa sensibilidad, especificidad y grado de asociación de cada prueba de confrontación en relación a Campimetría de Goldmann. Resultados: Las pruebas de mayor sensibilidad fueron las pruebas de comparación de dedos (58%) y comparación objeto color rojo (55%). Las pruebas de mayor especificidad fueron conteo de dedos (95%), movimiento del dedo en posición fija de la mano en diferentes cuadrantes (95%), movimiento de dedo desde la periferia al centro de los cuadrantes (93%) y la prueba de movimiento de pin rojo de 5 mm (93%). Las dos pruebas de mayor sensibilidad presentaron baja especificidad. Conclusiones: Los CVC se realizan de manera rutinaria en todos los pacientes neuroftalmológicos. Son pruebas de utilidad limitada para el tamizaje de patologías de vía visual por su baja sensibilidad pero las alteraciones detectadas son suficientemente específicas. Las de mayor utilidad fueron las pruebas dinámicas (mover de la periferia al centro el dedo o un pin rojo). Para confirmar el diagnóstico y hacer el seguimiento es necesario realizar pruebas objetivas como la Campimetría de Goldmann.

Veinticinco años de la Unidad de Neuro-oftalmología del Hospital Vargas de Caracas (1980-2005): apuntes para una biografía / Twenty five years of the Neuro-ophtalmologic Unit in the Vargas Hospital in Caracas (1980-2005)

Con la Unidad de Neuro-oftalmología del Hospital Vargas de Caracas se inicia en Venezuela el estudio de condiciones que afectan el órgano de la visión y sus relaciones con el sistema nervioso central. Fundada en 1980 con una idea asistencial-docente, se ha mantenido activa por más de 25 años y es única en su género en el país. Ha sustentado su ser y hacer en cuatro principios fundamentales, asistecia, docencia, investigación clínica y extensión. Asiste a enfermos del hospital y procedentes de diversos centros de la capital, así como también del interior del país, mediante una consulta externa gratuita muy activa en la cual se evalúan diariamente cerca de 16 pacientes de consulta sucesiva y 4 de primera de consulta. Luego y sobre la base de una experiencia clínica, progresó hacia la docencia de posgrado recibiendo por cortos períodos cerca de 40 pasantes por año entre oftalmólogos, neurológos y neuropediatras; adicionalmente se aceptan médicos especialistas para programa de "fellowship" en Neuro-Oftalmología de un año de duración. De esta manera han egresado 32 fellows, 24 venezolanos y 8 extranjeros: 26 oftalmológos, 3 neurólogos y médicos internistas. Con base en muestras de pacientes atendidos a lo largo de los años, se realiza investigación clínica continua de problemas neuro-oftalmológicos, lo cual ha permitido evaluar y desempeñar las diferencias regionales de algunas condiciones clínicas que adoptan características diferentes a otras latitudes. Porteriormente ha extendido su influencia extramuros con asistencia de su personal a otros hospitales para dictar cursos, charlas y ejercicios clínicos con pacientes, y en congresos y cursos internacionales

The systematic study of the conditions that affect the visual organ and its relations with the central nervous system began in this country with the Neuro-Ophthalmology Unit of the Vargas Hospital in Caracas, ascribed to the Department of Clinical Medicine “B” of the “José María Vargas” Medical School, attached to the Faculty of Medicine of the Central University of Venezuela. Founded in 1980 as a teaching clinic, the unit has stayed active for more than 25 years and is unique in its field. It has maintained its place based on four fundamental principles: assistance, education, clinical research and expansion. It treats patients from the Vargas Hospital and from other centers of the country, through an active external consultation scheme, free of charge, in which close to 16 follow-up patients and 4 first-time patients are tended to daily. Subsequently, based on extensive clinical experience, the Unit progressed in to post-graduate education, receiving close to 40 residents from ophthalmology, neurology and neuro-pediatrics programs each year for short periods for direct and supervised teaching. Additionally, especialists have been accepted for a one-year “fellowship” program in Neuro-Ophthalmology. Thirty-two fellows (24 Venezuelans and 8 foreigners) have graduated from this program: 26 ophthalmologists, 3 neurologists and 4 internists, many of which will assume taching duties in their own countries. Over the years, based on a sample of treated patients, continued clinical research of neuro-ophthalmologic problems is undertaken, which has allowed the evaluation, unraveling and publishing of the regional differences of certain clinical conditions. Subsequently, with the assistance of its personnel, the Unit has expanded its influence to other hospitals as well as national and international institutions, running courses and lectures and conducting clinical exercises with patients

Historia de la neurooftalmología / History of Neuroophthalmology

Se hace una introducción para explicar la dedicación de este número de la Revista Cubana de Oftalmología a la Neurooftalmología y se expone su desarrollo tomando en consideración los estudios de los elementos anatómicos y fisiológicos que constituyen su base, técnicas de exploración y las personalidades e instituciones, que a través de los años, en el mundo, y en Cuba, han contribuido a su desarrollo.

An introduction is made to explain why this issue of the Revista Cubana de Oftalmología is devoted to Neuroophthalmology. Its development is exposed taking into consideration the studies of the anatomical and physiological elements that constitute its basis, the exploratory techniques and the personalities and institutions that through the years have contributed to its development in Cuba and in the world.