Síndromes paraneoplásicos en oftalmología / Paraneoplastic syndromes in ophthalmology

Los síndromes paraneoplásicos consisten en la afectación de órganos y tejidos alejados de un tumor primario, y que no son consecuencia directa de la invasión tumoral ni de sus metástasis. Se sabe que en su fisiopatología desempeñan un papel importante la autoinmunidad y la síntesis de autoanticuerpos debido a un proceso de mimetismo molecular. Los síndromes paraneoplásicos de afectación oftalmológica son una enfermedad poco frecuente, pero es importante reconocerlos clínicamente debido a que en algunas ocasiones los síntomas derivados preceden al diagnóstico de la neoplasia de base. El tumor más frecuentemente relacionado con esta enfermedad es el carcinoma microcítico pulmonar, pero también existe relación con otras etiologías tumorales como el timoma, los tumores ginecológicos o el neuroblastoma en niños. Los síndromes paraneoplásicos de afectación oftalmológica pueden dividirse entre los que afectan a la vía visual aferente, como la retinopatía asociada al cáncer, la retinopatía asociada al melanoma o la neuropatía óptica paraneoplásica; o a la vía visual eferente, como las pupilas tónicas bilaterales, la miastenia gravis, el síndrome de Lambert-Eaton o la degeneración cerebelosa paraneoplásica. Cada vez se conocen más autoanticuerpos relacionados y su positividad es de ayuda en la práctica clínica, pero la negatividad no excluye el diagnóstico. Aunque su evolución y pronóstico va ligado al de la enfermedad causal, en algunos casos el tratamiento específico, habitualmente mediante terapia inmunosupresora puede ayudar a mejorar la calidad de vida de estos pacientes (AU)

Paraneoplastic syndromes consist on systemic manifestations associated with certain cancers which are not a direct consequence of tumor invasion or its metastases. It is known that autoimmunity and autoantibody synthesis play an important role in its pathophysiology due to a process of molecular mimicry. Paraneoplastic syndromes in ophthalmology are rare, but it is important to recognize them clinically because in some cases symptoms preceded the diagnosis of an underlying neoplasia. Most frequently involved cancer is small cell lung carcinoma, but there is also a relationship with other tumor etiologies such as thymoma, gynecological tumors or neuroblastoma in children. Paraneoplastic syndromes with ocular involvement can be divided into those that affect the afferent visual pathway, such as cancer-associated retinopathy, melanoma-associated retinopathy, or paraneoplastic optic neuropathy; and the ones that affect the efferent visual pathway, such as bilateral tonic pupils, Myasthenia Gravis, Lambert-Eaton syndrome or paraneoplastic cerebellar degeneration. The presence of autoantibodies is helpful in clinical practice but negativity does not exclude this diagnosis. Although evolution and prognosis is linked to primary disease, in some cases specific treatment, usually immunosuppressive therapy, can help improving patients quality of life (AU)

Paraneoplastic syndromes in ophthalmology.

Paraneoplastic syndromes consist on systemic manifestations associated with certain cancers which are not a direct consequence of tumor invasion or its metastases. It is known that autoimmunity and autoantibody synthesis play an important role in its pathophysiology due to a process of molecular mimicry. Paraneoplastic syndromes in ophthalmology are rare, but it is important to recognize them clinically because in some cases symptoms preceded the diagnosis of an underlying neoplasia. Most frequently involved cancer is small cell lung carcinoma, but there is also a relationship with other tumor etiologies such as thymoma, gynecological tumors or neuroblastoma in children. Paraneoplastic syndromes with ocular involvement can be divided into those that affect the afferent visual pathway, such as cancer-associated retinopathy, melanoma-associated retinopathy, or paraneoplastic optic neuropathy; and the ones that affect the efferent visual pathway, such as bilateral tonic pupils, Myasthenia Gravis, Lambert-Eaton syndrome or paraneoplastic cerebellar degeneration. The presence of autoantibodies is helpful in clinical practice but negativity does not exclude this diagnosis. Although evolution and prognosis is linked to primary disease, in some cases specific treatment, usually immunosuppressive therapy, can help improving patients quality of life.

Visual impairment induced by prosthetic cobaltism.

The case of a 68-year-old patient with visual loss secondary to prosthetic cobaltism is reported. The degeneration of the metallic hip prosthesis can produce a systemic absorption of cobalt with cardiac, neurological, endocrine, auditory, and visual manifestations. The diagnostic suspicion is confirmed by serum cobalt measurements. Treatment with early surgery and chelating agents can lead to improvement of the visual, and the other disorders.

Afectación visual por cobaltismo protésico / Visual impairment induced by prosthetic cobaltism

Se presenta el caso de un paciente de 68 años con pérdida visual secundaria a cobaltismo protésico. La degeneración de la prótesis metálica de cadera produce una absorción sistémica de cobalto con manifestaciones cardíacas, neurológicas, endocrinas, auditivas y visuales. La sospecha diagnóstica es confirmada mediante determinaciones séricas de cobalto, y un tratamiento con cirugía precoz y agentes quelantes puede generar una mejoría visual y del resto de síntomas (AU)

The case of a 68-year-old patient with visual loss secondary to prosthetic cobaltism is reported. The degeneration of the metallic hip prosthesis can produce a systemic absorption of cobalt with cardiac, neurological, endocrine, auditory, and visual manifestations. The diagnostic suspicion is confirmed by serum cobalt measurements. Treatment with early surgery and chelating agents can lead to improvement of the visual, and the other disorders (AU)

Neuritis ópticas desmielinizantes y autoinmunes / Autoimmune and demyelinating optic neuritis

El conocimiento sobre las neuropatías ópticas desmielinizantes y autoinmunes ha experimentado una revolución en la útima década tras el descubrimiento de los anticuerpos antiacuaporina 4 (AQP4). Las mejoras en las técnicas diagnósticas, el descubrimiento de nuevas dianas y el avance de la neuroinmunología han permitido la detección de anticuerpos asociados a las enfermedades desmielinizantes. Se presenta una revisión de los conceptos clásicos y nuevos de las neuritis ópticas desmielinizantes y autoimmunes. Se describe el debate en las constantes reformulaciones de su clasificación. Asimismo se actualizan los criterios diagnósticos de la esclerosis múltiple y de la neuromielitis óptica. Finalmente, se presentan los nuevos conceptos sobre las MOGopatías y las neuropatías opticas inflamatorias crónico-recurrentes (CRION)

The knowledge on demyelinating and autoimmune optic neuropathies has experienced a revolution the last decade since the discovery of anti-aquaporin 4 antibody. Improvements in diagnostic techniques, and the finding of new targets, along with advances in neuro-immunology have led to the detection of antibodies related to demyelinating diseases. A review is presented on the classical and new concepts in optic neuritis. The debate on the classification of demyelinating and autoimmune optic neuritis is presented. Furthermore, the updated diagnostic criteria in multiple sclerosis and neuro-myelitis optics are described. Finally, the latest insights into Myelin Oligodendrocyte Glycoprotein (MOG) disorders and chronic-recurring optic neuropathies (CRION) are highlited

Autoimmune and demyelinating optic neuritis. / Neuritis ópticas desmielinizantes y autoinmunes.

The knowledge on demyelinating and autoimmune optic neuropathies has experienced a revolution the last decade since the discovery of anti-aquaporin 4 antibody. Improvements in diagnostic techniques, and the finding of new targets, along with advances in neuro-immunology have led to the detection of antibodies related to demyelinating diseases. A review is presented on the classical and new concepts in optic neuritis. The debate on the classification of demyelinating and autoimmune optic neuritis is presented. Furthermore, the updated diagnostic criteria in multiple sclerosis and neuro-myelitis optics are described. Finally, the latest insights into Myelin Oligodendrocyte Glycoprotein (MOG) disorders and chronic-recurring optic neuropathies (CRION) are highlited.

Impacto sobre la cirugía electiva en oftalmología ocasionado por la pandemia de la COVID-19 tras el cese del estado de alarma en el Instituto Clínico de Oftalmología del Hospital Clinic de Barcelona / Impact on elective ophthalmic surgery caused by the COVID-19 pandemic after the lockdown at the Clinical Institute of Ophthalmology of the Hospital Clinic de Barcelona

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Compressive optic neuropathy secondary to an allergic reaction to hyaluronidase. / Neuropatía óptica compresiva secundaria a reacción alérgica a hialuronidasa.

A 58 year-old woman presented with severe chemosis and ophthalmoparesis on her left eye 8hours after uncomplicated cataract surgery under sub-tenon anaesthesia. Recovery of extrinsic motility was observed after corticosteroid and antihistamine treatment, but a non-haemorrhagic papillary oedema and a concentric defect of visual field were found. It progressed to papillary atrophy with preserved central vision, but with a significant visual field constriction. The aetiological study revealed an allergy to hyaluronidase that was used as adjuvant to the anaesthesia. This complication needs to be promptly diagnosed and treated, as the swelling of the orbital tissues can cause damage to the optic nerve.

Ocular surface adverse events of systemic epidermal growth factor receptor inhibitors (EGFRi): A prospective trial.

PURPOSE: Controversy exists regarding the safety of agents that systemically inhibit epidermal growth factor receptor (EGFRi) in oncologic patients in terms of toxicity to the ocular surface. We performed a prospective clinical study comparing the ocular surface toxicity of systemic EGFRi between a case and a control group. METHODS: Patients with lung or colon cancer were divided in two groups: 25 patients treated with systemic EGFRi and 25 control patients without EGFRi treatment. Patients in both groups were chemotherapy naive. Four visits were scheduled in a one year period comparing signs and symptoms in terms of symptom questionnaires (SIDEQ, OSDI and AVS), corneal fluorescein staining (Oxford test), tear production (Schirmer's test) and a quantitative evaluation of conjunctival chemosis and hyperemia. Basal epithelial cell density (CEBD) and corneal subepithelial nerve fiber density (CNFD) were measured and compared using confocal microscopy (Heidelberg Engineering, Germany). The differences in each variable were compared with the analysis of variance (ANOVA). A P value<0.05 was considered significant for all comparisons. RESULTS: No statistically significant differences were found between patients under EGFRi treatment and the age-matched controls in the variables analyzed. When cases and controls were evaluated separately, the case group showed a significantly worse progression of signs (chemosis score, CFS, Schirmer's) as well as in terms of CEBD and CNFD (all P<0.05). CONCLUSION: Systemic EGFRi may increase dry eye signs as well as decrease CEBD and CNFD. This study may help us to understand the true toxicity of EGFRi to the ocular surface.

Color vision impairment in multiple sclerosis points to retinal ganglion cell damage.

Multiple Sclerosis (MS) results in color vision impairment regardless of optic neuritis (ON). The exact location of injury remains undefined. The objective of this study is to identify the region leading to dyschromatopsia in MS patients' NON-eyes. We evaluated Spearman correlations between color vision and measures of different regions in the afferent visual pathway in 106 MS patients. Regions with significant correlations were included in logistic regression models to assess their independent role in dyschromatopsia. We evaluated color vision with Hardy-Rand-Rittler plates and retinal damage using Optical Coherence Tomography. We ran SIENAX to measure Normalized Brain Parenchymal Volume (NBPV), FIRST for thalamus volume and Freesurfer for visual cortex areas. We found moderate, significant correlations between color vision and macular retinal nerve fiber layer (rho = 0.289, p = 0.003), ganglion cell complex (GCC = GCIP) (rho = 0.353, p < 0.001), thalamus (rho = 0.361, p < 0.001), and lesion volume within the optic radiations (rho = -0.230, p = 0.030). Only GCC thickness remained significant (p = 0.023) in the logistic regression model. In the final model including lesion load and NBPV as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia [OR = 0.88 95 % CI (0.80-0.97) p = 0.016]. This association remained significant when we also added sex, age, and disease duration as covariates in the regression model. Dyschromatopsia in NON-eyes is due to damage of retinal ganglion cells (RGC) in MS. Color vision can serve as a marker of RGC damage in MS.

The visual pathway as a model to understand brain damage in multiple sclerosis.

Patients with multiple sclerosis (MS) almost always experience effects in the visual pathway; and thus, visual dysfunction is not only common but also highly relevant. The visual pathway represents a model of acute focal central nervous system (CNS) damage, through acute optic neuritis and retinal periphlebitis, as well as a model of chronic, diffuse CNS damage through chronic retinopathy and optic neuropathy. The optic pathway can be accurately evaluated in detail, due to the availability of highly sensitive imaging techniques (e.g. magnetic resonance imaging or optical coherent tomography) or electrophysiological tests (multifocal visual evoked potentials or electroretinography). These techniques allow the interactions between the different processes at play to be evaluated, such as inflammation, demyelination, axonal damage and neurodegeneration. Moreover, these features mean that the visual pathway can be used as a model to test new neuroprotective or regenerative therapies.

Is the incidence of optic neuritis rising? Evidence from an epidemiological study in Barcelona (Spain), 2008-2012.

It is currently believed that the incidence rate of optic neuritis (ON) ranges between 0.56 and 5.1 cases per 100,000 person-years. However, since these figures were generated, they have not been updated and there are suggestions that the incidence of ON is on the rise. When designing new therapies and clinical trials for ON, and to improve the management this disease, it is important to have accurate epidemiological data. Thus, we set out to obtain the prevalence and incidence rates of ON in Barcelona (Spain) from 2008 to 2012, by a retrospective evaluation of electronic hospital records at the Hospital Clinic of Barcelona (population of 300,000 in the catchment area) matching the following ICD-9-CM codes as search terms: 377.3-optic neuritis; 377.30-optic neuritis, unspecific; 377.31-optic papillitis; 377.32-retrobulbar neuritis, acute; 377.39-other optic neuritis and "optic neuropathy". Demographic and clinical data were collected from records with a confirmed diagnosis of ON, including cases of idiopathic ON, multiple sclerosis, neuromyelitis optica and CRION. The prevalence of acute ON on 31 December 2012 was 2.75 cases per 100,000 people. The mean annual prevalence of acute ON during the 2008-2012 period was 7.87 cases per 100,000 person-year and the mean annual incidence rate was 5.36 cases per 100,000 person-years. The incidence of ON in Barcelona during 2008-2012 was higher than previously reported. This increase may reflect the evolution of diagnostic criteria, the use of a referral-center approach instead of a population-based approach, increased awareness of demyelinating diseases, latitude-related factors and possibly a true increase in its incidence.

Comparación de tres instrumentos de tomografía de coherencia ¨®ptica, un time-domain y dos Fourier-domain, en la estimación del grosor de la capa de fibras nerviosas de la retina / Comparison of three optical coherence tomography devices, one time-domain and two fourier-domain, for the estimation of the retinal nerve fibre layer thickness

Objetivo: Determinar la concordancia entre un sistema de tomografía de coherencia óptica (TCO) time-domain (Stratus) y dos sistemas de TCO Fourier-domain (Cirrus y 3D TCO-1000) en la determinacióndel grosor de la capa de fibras nerviosas de la retina (CFNR) Métodos: Se incluyeron 50 ojos de 25 pacientes con patología neurooftalmológica de la vía visual aferente. A todos los pacientes se les realizó en ambos ojos, el mismo día y por el mismo operario, un triple examen de TCO de la CFNR con Stratus, Cirrus y 3D TCO-1000. El grosor medio de la CFNR global, por cuadrantes y por sectores horarios fueron comparados mediante el coeficiente de concordancia de Lin (CCC) y figuras de Bland-Altman. Resultados: El grosor de la CFNR global, de los cuadrantes temporal y nasal y de los sectores horarios correspondientes estimado mediante 3D TCO-1000 fue el m¨¢s alto (global, 90,02 Alfa-Ìm), en cambio, el grosor de la CFNR en los cuadrantes superior e inferior y en los sectores horarios correspondientes fue mayor con Stratus. El CCC entre Stratus y Cirrus fue alto (0,820), en cambio, la concordancia entre Stratus y 3D TCO-1000 fue moderada globalmente (0,573) y entre Cirrus y 3D TCO-1000 result¨® moderada de forma global (0,564), pero muy baja en los cuadrantes nasal y temporal (0,362 y 0,347 respectivamente). Conclusiones: Los espesores medios de la CFNR obtenidos mediante los TCO Stratus, Cirrus y 3D TCO-1000 no son equivalentes. Aunque la concordancia entre Stratus y Cirrus es alta, entre 3D TCO-1000 y Stratus o Cirrus es muy baja(AU)

Purpose: To assess agreement between one system of time-domain optical coherence tomography (OCT) (Stratus) and two systems of fourier-domain OCT (Cirrus and 3D OCT-1000) for the measurement of the retinal nerve fibre layer thickness (RNFL). Methods: Fifty eyes from 25 patients with neuro-ophthalmological disorders of the afferent visual pathway were included. A triple RNFL thickness OCT examination with Stratus, Cirrus and 3D OCT-1000 was performed on both eyes of every patient, on the same day and by the same technician. The average RNFL thickness by quadrants and clock sectors were compared with the Lin´s concordance correlation coefficient (CCC) and Bland-Altman plots. Results: The average RNFL thickness, the temporal and nasal quadrants and corresponding clock sectors, was higher by 3D OCT-1000 (mean 90.02 microns), nevertheless, RNFL thickness of the superior and inferior quadrants and corresponding clock hours was higher when measured by Stratus device. The CCC agreement between Stratus and Cirrus was high (0.820), between Stratus and 3D OCT-1000 was moderate (mean 0.573) and between Cirrus and 3D OCT-1000 was moderate with a mean of 0.564 but too low in the nasal and temporal quadrants (0.362 and 0.347 respectively). Conclusions: The RNFL thickness measurements by Stratus, Cirrus and 3D OCT-1000 OCT are not equivalent. Although the agreement between Stratus and Cirrus was high, it was too low between 3D OCT-1000 and Stratus or Cirrus(AU)

[Comparison of three optical coherence tomography devices, one time-domain and two fourier-domain, for the estimation of the retinal nerve fibre layer thickness]. / Comparación de tres instrumentos de tomografía de coherencia óptica, un time-domain y dos Fourier-domain, en la estimación del grosor de la capa de fibras nerviosas de la retina.

PURPOSE: To assess agreement between one system of time-domain optical coherence tomography (OCT) (Stratus) and two systems of fourier-domain OCT (Cirrus and 3D OCT-1000) for the measurement of the retinal nerve fibre layer thickness (RNFL). METHODS: Fifty eyes from 25 patients with neuro-ophthalmological disorders of the afferent visual pathway were included. A triple RNFL thickness OCT examination with Stratus, Cirrus and 3D OCT-1000 was performed on both eyes of every patient, on the same day and by the same technician. The average RNFL thickness by quadrants and clock sectors were compared with the Lin´s concordance correlation coefficient (CCC) and Bland-Altman plots. RESULTS: The average RNFL thickness, the temporal and nasal quadrants and corresponding clock sectors, was higher by 3D OCT-1000 (mean 90.02 microns), nevertheless, RNFL thickness of the superior and inferior quadrants and corresponding clock hours was higher when measured by Stratus device. The CCC agreement between Stratus and Cirrus was high (0.820), between Stratus and 3D OCT-1000 was moderate (mean 0.573) and between Cirrus and 3D OCT-1000 was moderate with a mean of 0.564 but too low in the nasal and temporal quadrants (0.362 and 0.347 respectively). CONCLUSIONS: The RNFL thickness measurements by Stratus, Cirrus and 3D OCT-1000 OCT are not equivalent. Although the agreement between Stratus and Cirrus was high, it was too low between 3D OCT-1000 and Stratus or Cirrus.

[Neuro-ophthalmological manifestations of pituitary adenomas. The usefulness of optical coherence tomography]. / Manifestaciones neurooftalmológicas de los adenomas hipofisarios. Valor de la tomografía de coherencia óptica.

INTRODUCTION: Pituitary adenomas are a frequently occurring pathology that require multidisciplinary management by several different specialists. Their neuro-ophthalmological manifestations vary widely and sometimes appear as the presenting symptom. AIM: To gather the main ophthalmological signs and symptoms of these tumours so that specialists who find themselves before any of them will suspect this pathology. DEVELOPMENT: This survey was based on the clinical experience of the neuro-ophthalmological unit at the Hospital Clinic de Barcelona, with over 350 patients who had suffered from pituitary tumours. A bibliographical search was also carried out on Medline for papers published on pituitary adenomas in the literature in both English and Spanish. We focused mainly on those that reported on the ophthalmological manifestations of such tumours. A number of articles were found dealing with isolated ophthalmological manifestations of these tumours, many of them as presenting symptoms. We also found review articles in English. Apart from oculomotor disorders and other less common findings, visual field defects stand out as the guiding symptom of this condition. CONCLUSIONS: Improved diagnostic techniques are allowing pituitary tumours to be detected at increasingly earlier stages, but cases are still seen with neuro-ophthalmological symptoms as the presenting symptoms. Familiarity with these syndromes is crucial. In addition to the clinical and visual field examination, optical coherence tomography is particularly useful for the diagnosis and follow-up of these patients. Prospective studies are needed to establish factors for predicting the visual recovery in these patients.

Manifestaciones neurooftalmológicas de los adenomas hipofisarios. Valor de la tomografía de coherencia óptica / Neuro-ophthalmological manifestations of pituitary adenomas. The usefulness of optical coherence tomography

Introducción. Los adenomas hipofisarios son una patología frecuente. Requieren un tratamiento multidisciplinario entre varios especialistas. Sus manifestaciones neurooftalmológicas son muy variadas, y en ocasiones aparecen como síntoma de presentación. Objetivo. Reunir los principales signos y síntomas oftalmológicos de estos tumores, para que todo especialista sospeche esta patología cuando se encuentre ante alguno de ellos. Desarrollo. Esta revisión se ha desarrollado sobre la base de la experiencia clínica de la unidad de neurooftalmología del Hospital Clínic de Barcelona, con más de 350 pacientes afectos de tumores hipofisarios. Asimismo, se ha realizado una búsqueda bibliográfica en Medline de los artículos publicadossobre adenomas hipofisarios en lengua castellana e inglesa. Se centró principalmente en aquéllos que se referían a las manifestaciones oftalmológicas de dichos tumores. Se encontraron numerosos artículos referentes a manifestaciones oftalmológicas aisladas de estos tumores, muchas de ellas como inicio. También se encontraron artículos de revisión en lengua inglesa.Aparte de las alteraciones oculomotoras y otros hallazgos menos frecuentes, destacan las alteraciones campimétricas como síntoma guía de esta patología. Conclusiones. Los tumores hipofisarios se detectan cada vez más temprano debido a la mejora en las técnicas diagnósticas, pero aún se observan casos con síntomas neurooftalmológicos como inicio. Resulta crucialel conocimiento de estos síndromes. Además de la exploración clínica y la campimetría, la tomografía de coherencia óptica resulta de gran valor para el diagnóstico y el seguimiento de estos pacientes. Se necesitan estudios prospectivos para establecerfactores pronósticos de recuperación visual en estos pacientes

Introduction. Pituitary adenomas are a frequently occurring pathology that require multidisciplinary management by several different specialists. Their neuro-ophthalmological manifestations vary widely and sometimes appear as the presenting symptom. Aim. To gather the main ophthalmological signs and symptoms of these tumours so that specialists who find themselves before any of them will suspect this pathology. Development. This survey was based on the clinical experience of the neuro-ophthalmological unit at the Hospital Clínic de Barcelona, with over 350 patients who had suffered from pituitary tumours. A bibliographical search was also carried out on Medline for papers published on pituitary adenomas in the literature in both English and Spanish. We focused mainly on those that reported on the ophthalmological manifestations ofsuch tumours. A number of articles were found dealing with isolated ophthalmological manifestations of these tumours, many of them as presenting symptoms. We also found review articles in English. Apart from oculomotor disorders and other less common findings, visual field defects stand out as the guiding symptom of this condition. Conclusions. Improved diagnostictechniques are allowing pituitary tumours to be detected at increasingly earlier stages, but cases are still seen with neuroophthalmological symptoms as the presenting symptoms. Familiarity with these syndromes is crucial. In addition to the clinical and visual field examination, optical coherence tomography is particularly useful for the diagnosis and follow-up ofthese patients. Prospective studies are needed to establish factors for predicting the visual recovery in these patients

[Papilledema as an indicator of POEMS syndrome]. / Papiledema asociado a síndrome de POEMS.

CASE REPORT: We present the case of a 54-year-old woman with papilledema associated to POEMS syndrome. The presence of intracranial hypertension was detected and treatment started with acetazolamide. DISCUSSION: The most common ophthalmological pathology in POEMS syndrome is papilledema, the etiology of which could be infiltrative, intracranial hypertension, inflammation or an increase of the vascular permeability. The correct diagnosis and treatment of papilledema, depending on its etiology, should permit an acceptable visual outcome to be achieved.