RESUMEN
As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.
Asunto(s)
Clemastina , Glaucoma , Ratones Endogámicos C57BL , Remielinización , Retina , Animales , Clemastina/farmacología , Clemastina/uso terapéutico , Glaucoma/patología , Glaucoma/tratamiento farmacológico , Retina/patología , Retina/efectos de los fármacos , Remielinización/efectos de los fármacos , Remielinización/fisiología , Ratones , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Modelos Animales de Enfermedad , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/patología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patologíaRESUMEN
PURPOSE: To assess the effectiveness of tocilizumab in reverting the signs and symptoms of dysthyroid optic neuropathy (DON) in thyroid eye disease and the need for emergency orbital decompression. The secondary outcomes are to identify the optimal number of tocilizumab cycles to achieve the primary outcome, to analyze the association between thyroid stimulating immunoglobulin (TSI), clinical activity score (CAS) and proptosis in response to the treatment and the need for rehabilitative orbital decompression. METHODS: Prospective longitudinal cohort study that included 13 patients who had unilateral or bilateral dysthyroid optic neuropathy (DON) due to severe and progressive sight-threatening thyroid eye disease based on the CAS system. Patients were seen in this facility starting from July 2017, and all had received intravenous tocilizumab. RESULTS: Initial visual acuity mean was 0.52 ± 0.38 and the final were 0.93 ± 0.11 with a mean difference of 0.41 and P < 0.00245. The mean CAS prior to the initiation of the treatment was 7.92 ± 0.66 and the final was 2.85 ± 1.03 with mean difference of 5.07 and P < 0.00001. Initial mean proptosis was 24.85 ± 2.31 and the final was 21.78 ± 2.18 with a mean difference of 3.07 and P < 0.000497. No emergency orbital decompression was performed. TSI was high initially in all cases with a wide range of 2.4 to 40 IU/L and with a mean of 10.70 ± 13.40. The final TSI mean was 2.90 ± 3.90 with a mean difference of 7.81 and significant P value (P < 0.0272). CONCLUSION: Tocilizumab use in optic nerve compression showed promising results as it can be the primary or an alternative treatment option.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Oftalmopatía de Graves , Agudeza Visual , Humanos , Estudios Prospectivos , Masculino , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Oftalmopatía de Graves/complicaciones , Oftalmopatía de Graves/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Enfermedades del Nervio Óptico/etiología , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Descompresión Quirúrgica/métodos , Estudios de Seguimiento , Anciano , Resultado del Tratamiento , Síndromes de Compresión Nerviosa/etiología , Síndromes de Compresión Nerviosa/tratamiento farmacológico , Síndromes de Compresión Nerviosa/diagnósticoRESUMEN
OBJECTIVE: To investigate the changes in macular vessel density (VD) of the superficial layer of retina (SLR) and deep layer of retina (DLR) in dysthyroid optic neuropathy (DON) after high-dose intravenous pulse methylprednisolone (IVMP). MATERIALS AND METHODS: Eighteen DON patients (29 eyes) who completed high-dose IVMP and 16 healthy individuals (32 eyes) were enrolled in this study. Optical coherence tomography angiography (OCTA) image analysis and comprehensive ophthalmic examinations were performed, including the SLR macular whole-image VD (SLR-mwiVD) and DLR-mwiVD, best-corrected visual acuity (BCVA), the mean deviation of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD) and the other parameters. RESULTS: The SLR-mwiVD (41.39 ± 4.71 vs. 48.13 ± 3.68, p < 0.001) and DLR-mwiVD (40.77 ± 5.85 vs. 49.14 ± 7.02, p < 0.001) were decreased in DON compared to control eyes. After IVMP, visual function parameters were improved, and SLR-mwiVD (49.41 ± 3.18, p < 0.001) and DLR-mwiVD (50.41 ± 4.04, p < 0.001) were increased in the DON group compared to pretreatment. The increased SLR-mwiVD and DLR-mwiVD were significantly correlated with improvements in BCVA (Log MAR: from 0.62 ± 0.49 to -0.01 ± 0.03, p < 0.001), VF-MD (from - 6.89 ± 2.89 dB to - 1.75 ± 1.29 dB, p < 0.001) and VF-PSD (from 4.38 ± 2.52 dB to 2.32 ± 1.64 dB, p < 0.001). CONCLUSION: The increase in macular VD was significantly correlated with the improvement in visual function in DON after IVMP. Macular VD changes on OCTA may be a useful indicator for the response in DON after IVMP.
Asunto(s)
Disco Óptico , Enfermedades del Nervio Óptico , Fotoquimioterapia , Humanos , Disco Óptico/irrigación sanguínea , Angiografía con Fluoresceína/métodos , Vasos Retinianos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Enfermedades del Nervio Óptico/tratamiento farmacológicoRESUMEN
Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.
Asunto(s)
Glaucoma , Enfermedades del Nervio Óptico , Humanos , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/etiología , Glaucoma/metabolismo , Células Ganglionares de la Retina/metabolismo , Vitaminas , Suplementos DietéticosRESUMEN
Programmed axon death is a druggable pathway of axon degeneration that has garnered considerable interest from pharmaceutical companies as a promising therapeutic target for various neurodegenerative disorders. In this review, we highlight mechanisms through which this pathway is activated in the retina and optic nerve, and discuss its potential significance for developing therapies for eye disorders and beyond. At the core of programmed axon death are two enzymes, NMNAT2 and SARM1, with pivotal roles in NAD metabolism. Extensive preclinical data in disease models consistently demonstrate remarkable, and in some instances, complete and enduring neuroprotection when this mechanism is targeted. Findings from animal studies are now being substantiated by genetic human data, propelling the field rapidly toward clinical translation. As we approach the clinical phase, the selection of suitable disorders for initial clinical trials targeting programmed axon death becomes crucial for their success. We delve into the multifaceted roles of programmed axon death and NAD metabolism in retinal and optic nerve disorders. We discuss the role of SARM1 beyond axon degeneration, including its potential involvement in neuronal soma death and photoreceptor degeneration. We also discuss genetic human data and environmental triggers of programmed axon death. Lastly, we touch upon potential therapeutic approaches targeting NMNATs and SARM1, as well as the nicotinamide trials for glaucoma. The extensive literature linking programmed axon death to eye disorders, along with the eye's suitability for drug delivery and visual assessments, makes retinal and optic nerve disorders strong contenders for early clinical trials targeting programmed axon death.
Asunto(s)
Proteínas del Dominio Armadillo , Axones , Nicotinamida-Nucleótido Adenililtransferasa , Enfermedades del Nervio Óptico , Humanos , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/fisiopatología , Enfermedades del Nervio Óptico/metabolismo , Axones/fisiología , Nicotinamida-Nucleótido Adenililtransferasa/metabolismo , Animales , Proteínas del Dominio Armadillo/metabolismo , Proteínas del Citoesqueleto/metabolismo , Apoptosis/fisiología , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/fisiopatología , NAD/metabolismoRESUMEN
Optic neuropathy can be of infectious or non-infectious/idiopathic aetiology. Many infectious organisms can cause optic neuropathy that can be of varied presentation including papillitis, retrobulbar optic neuritis, neuroretinitis, and optic perineuritis. Detailed history, ocular, systemic/neurologic examination along with appropriate laboratory evaluation can help clinicians to identify the infectious agent causing optic neuropathy. In spite of recent advanced techniques in serological testing and molecular diagnostics like polymerase chain reaction (PCR), the identification of these pathogens is still a diagnostic challenge. It is ideal to have an infectious disease (ID) consultant in the management team, as most of these infections are multisystem involving diseases. Most infectious agents can be effectively treated with specific antibiotics, with or without corticosteroid therapy, but visual recovery is highly variable and depends entirely on early diagnosis of the causative agent. This review article will provide an overview of common pathogens involved in ION and will describe their management paradigms.
Asunto(s)
Enfermedades del Nervio Óptico , Humanos , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/microbiología , Enfermedades del Nervio Óptico/tratamiento farmacológico , Antibacterianos/uso terapéutico , Neuritis Óptica/diagnóstico , Neuritis Óptica/microbiología , Neuritis Óptica/tratamiento farmacológico , Infecciones del Ojo/diagnóstico , Infecciones del Ojo/microbiología , Infecciones del Ojo/tratamiento farmacológicoRESUMEN
ABSTRACT Purpose: To evaluate the prevalence, clinical characteristics, and types of optic nerve involvement in patients with ocular toxoplasmosis. Methods: For this retrospective cross-sectional study, we examined all patients with active ocular toxoplasmosis referred to our Uveitis Section during the last 12 years, and we included patients with optic nerve involvement in the study. The primary outcome was the prevalence of optic nerve involvement, and secondary outcomes included the types of optic nerve involvement and the final best-corrected visual acuity after treatment. Results: The prevalence of optic nerve involvement was 14.4%, with the leading cause being the activation of a juxtapapillary lesion (70.5%). We found papillitis in two eyes and neuroretinitis in two eyes (11.7% for each). We only detected one optic nerve involvement secondary to a distant active lesion (5.8%). Sixteen patients (94.1%) had unilateral ocular toxoplasmosis. The overall final best-corrected visual acuity after treatment was 10/10 (LogMAR = 0.0) excluding the three patients with a juxtapapillary scar involving the macula. Conclusions: Optic nerve involvement was common in patients with ocular toxoplasmosis. The main type of optic nerve involvement was caused by activation of an old juxtapapillary lesion. Treatment was quickly effective, but the best-corrected visual acuity was dependent on the presence of a scar in the papillomacular bundle.
RESUMO Objetivos: Avaliar a prevalência, características clínicas e tipos de acometimento do nervo óptico em pacientes com toxoplasmose ocular. Métodos: Para este estudo retrospectivo transversal, examinamos todos os pacientes com toxoplasmose ocular ativa encaminhados ao nosso Setor de Uveíte nos últimos 12 anos, e incluímos pacientes com comprometimento do nervo óptico no estudo. O resultado primário foi a prevalência do envolvimento do nervo óptico, e os resultados secundários incluíram os tipos de envolvimento do nervo óptico e a acuidade visual final melhor corrigida após o tratamento. Resultados: A prevalência de acometimento do nervo óptico foi 14,4%, sendo a principal causa a ativação de uma lesão justapapilar (70,5%). Encontramos papilite em dois olhos e neuroretinite em dois olhos (11,7% para cada um). Apenas detectamos um comprometimento do nervo óptico secundário a uma lesão ativa distante (5,8%). Dezesseis pacientes (94,1%) apresentavam toxoplasmose ocular unilateral. A acuidade visual final com melhor correção após o tratamento foi 10/10 (LogMAR= 0,0) excluindo os três pacientes com uma cicatriz justapapilar envolvendo a mácula. Conclusões: O comprometimento do nervo óptico foi comum em pacientes com toxoplasmose ocular. O principal tipo de comprometimento do nervo óptico foi causado pela ativação de uma lesão justapapilar antiga. O tratamento foi rapidamente eficaz, mas a acuidade visual final com melhor correção foi dependente da presença de uma cicatriz no feixe papilomacular.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Adulto Joven , Enfermedades del Nervio Óptico/parasitología , Enfermedades del Nervio Óptico/patología , Toxoplasmosis Ocular/patología , Nervio Óptico/patología , Nervio Óptico/diagnóstico por imagen , Retinitis/parasitología , Retinitis/patología , Factores de Tiempo , Turquía/epidemiología , Agudeza Visual , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/epidemiología , Papiledema/parasitología , Papiledema/patología , Toxoplasmosis Ocular/tratamiento farmacológico , Prevalencia , Estudios Transversales , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Centros de Atención TerciariaRESUMEN
We described a 35 years old female patient with bilateral visual loss and pain on eye movement, mild papillary edema in acute phase, arcuate scotoma and complementary test positive for antinuclear antibodies that did not respond to corticosteroid therapy. The lack of clinical criteria for systemic lupus erythematosus (SLE) didn't prevent the institution of the specific treatment with corticosteroids and azathioprine. After seven months the diagnosis was made after a skin manifestation of the disease. This case shows the value of the ocular complaints in systemic diseases. And how the ophthalmologic exam can help the clinician elaborating a diagnosis. It is also very important for ophthalmologists and rheumatologists due to the fact that it calls the attention to another diagnostic hypothesis in patients with nonspecific optic neuritis, even with inconclusive laboratory tests. Maybe some ocular findings deserve to be included to the diagnostic criteria already established for SLE.
Descrevemos caso de um paciente de 35 anos do sexo feminino, com perda visual bilateral associada à dor à movimentação ocular, edema papilar moderado na fase aguda, escotoma arqueado e exame complementar positivo para anticorpos antinucleares, que não responderam à terapia com corticosteróides. A falta de critérios clínicos para o lúpus eritematoso sistêmico (LES) não impediu a instituição do tratamento específico com corticosteróides e azatioprina. Depois de sete meses, o diagnóstico foi feito após uma manifestação da doença de pele. Este caso mostra o valor das queixas oculares em doenças sistêmicas e como o exame oftalmológico pode ajudar o clínico na elaboração de um diagnóstico. Também é muito importante para oftalmologistas e reumatologistas, devido ao fato de que chama a atenção para outra hipótese diagnóstica em pacientes com neurite óptica não-específica, mesmo com os testes laboratoriais conclusivos. Talvez alguns achados oculares merecem ser incluídos com os critérios de diagnóstico já estabelecido para o LES.
Asunto(s)
Humanos , Femenino , Adulto , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiología , Enfermedades del Nervio Óptico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Oftalmoscopía , Nervio Óptico/patología , Pregnenodionas/uso terapéutico , Piel/patología , Azatioprina/uso terapéutico , Biopsia , Proteína C-Reactiva/metabolismo , Prednisolona/uso terapéutico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Papiledema/patología , Anticuerpos Antinucleares/sangre , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
Se realizó una revisión bibliográfica con el objetivo de proporcionar una actualización de las drogas que se emplean para retrasar la aparición de esclerosis múltiple en el manejo de la neuropatía óptica inflamatoria desmielinizante. El artículo presenta el origen y la justificación de la terapia esteroidea en este grupo de enfermedad, así como los mecanismos de acción y beneficios de tratamientos más modernos como los inmunomoduladores e inmunosupresores. El trabajo también introduce muchas de las drogas con efectos neuroprotectores que se encuentran en fases experimentales, cuyo uso prevendría la neurodegeneración que se produce a nivel de las células ganglionares retinianas en esta enfermedad neurológica. Las opciones terapéuticas actuales ofrecen variantes de tratamiento adicionales a pacientes con mayores probabilidades de desarrollo de esclerosis múltiple y retrasan la aparición de un segundo brote, así como las secuelas invalidantes que esta suele originar
A bibliographic review was conducted to provide an updating of drugs used to retard the appearance of multiple sclerosis in the management of the demyelinating inflammatory optical neuropathy. Present paper shows the origin and the justification of the steroid therapy in this disease, as well as the mechanisms of action and benefits of more recent treatments, e.g. the ongoing immunomodulations and immunosuppressive ones and also to introduce many drugs in experimental phase having neuroprotection effects whose use will prevent the neurodegenerative effect produced at level of the retinal ganglion cells in this neurologic disease. The current therapeutical options offer variants of additional treatment to those patients with greater possibilities to development multiple sclerosis and retarding the appearance of a second outbreak, as well as its disabling sequelae
Asunto(s)
Humanos , Masculino , Femenino , Enfermedades del Nervio Óptico/tratamiento farmacológico , Esclerosis Múltiple/etiología , Esclerosis Múltiple/prevención & control , Esteroides/uso terapéutico , Terapia Biológica/métodosRESUMEN
Dysthyroid optic neuropathy is an uncommon and severe form of presentation of Graves ophtalmopathy, caused by compression and elongation of the optic nerve. Use of high dose steroids is the treatment of choice. Decompressive surgery is reserved for refractory cases. We report a 41 years old female with a dysthyroid optic neuropathy that appeared 18 years after the diagnosis of Graves disease, manifested by a marked reduction in visual acuity. Orbit CAT scan did not show compression or elongation of optic nerve. She was treated with prednisone 60 mg per day, obtaining a complete remission after 19 days of treatment. After 90 days of follow up with low doses of steroids, the patient remains asymptomatic.