RESUMO
SIGNIFICANCE: Leber's hereditary optic neuropathy (LHON) is often associated with onset in the young, adult male demographic. This case report serves as a reminder that it can affect both sexes with onset into middle age. PURPOSE: Leber's hereditary optic neuropathy is a maternally inherited mitochondrial disorder that typically affects men during young adulthood. It presents with a rapid, yet painless loss of vision, with the fellow eye often affected within a few months. The optic neuropathy causes a dense central scotoma with visual acuities reduced to less than 20/400. CASE REPORT: A 60-year-old White woman presented with reports of decreased vision in both eyes for the previous 2 months. She had been followed up for the previous 5 years for glaucoma suspect monitoring, with full fields and normal optical coherence tomography scans. Entering visual acuity was finger counting at 1 m in the right eye and 20/100 in the left eye. Pupil testing revealed a grade 1 relative afferent pupillary defect in the right eye. Dilated fundus examination revealed stable moderate optic nerve cupping and intact neuroretinal rim tissue. Humphrey 24-2 Swedish Interactive Thresholding Algorithm standard visual field testing showed a significant superior altitudinal defect and inferior paracentral defect in the right eye and a partial superior arcuate in the left eye. The result of the MRI with contrast of the head and orbits was normal. A history of alcoholism was elicited, and LHON testing revealed positive 11778 mutation at homoplasmy. CONCLUSIONS: Although still uncommon, presentation of LHON in a middle-aged woman is possible and should be considered a viable differential diagnosis when individuals present with painless vision loss and central/centrocecal scotomas.
Assuntos
Atrofia Óptica Hereditária de Leber , Doenças do Nervo Óptico , Feminino , Humanos , Pessoa de Meia-Idade , Fundo de Olho , Atrofia Óptica Hereditária de Leber/diagnóstico , Atrofia Óptica Hereditária de Leber/genética , Escotoma/diagnóstico , Escotoma/etiologia , Testes de Campo VisualRESUMO
BACKGROUND: Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis. METHODS: We assessed the retinal and visual function in 12 patients (aged 8-44 years) with RPE65-associated Leber's congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1.5 x 10(10) vector genomes), medium (4.8 x 10(10) vector genomes), or high dose (1.5 x 10(11) vector genomes) for up to 2 years. FINDINGS: AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. The study is registered with ClinicalTrials.gov, number NCT00516477. INTERPRETATION: The safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain. FUNDING: Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia, Foundation Fighting Blindness, Telethon, Research to Prevent Blindness, F M Kirby Foundation, Mackall Foundation Trust, Regione Campania Convenzione, European Union, Associazione Italiana Amaurosi Congenita di Leber, Fund for Scientific Research, Fund for Research in Ophthalmology, and National Center for Research Resources.
Assuntos
Proteínas de Transporte/genética , Proteínas do Olho/genética , Terapia Genética/métodos , Atrofia Óptica Hereditária de Leber/terapia , Adolescente , Adulto , Fatores Etários , Cegueira/congênito , Cegueira/genética , Criança , Adaptação à Escuridão , Dependovirus/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Eletrorretinografia , Feminino , Vetores Genéticos/genética , Vetores Genéticos/uso terapêutico , Humanos , Injeções , Masculino , Mutação/genética , Nistagmo Fisiológico , Atrofia Óptica Hereditária de Leber/diagnóstico , Atrofia Óptica Hereditária de Leber/genética , Segurança , Resultado do Tratamento , Acuidade Visual , Adulto Jovem , cis-trans-IsomerasesRESUMO
Objetivo: Determinar la eficacia del tratamiento con idebenona y multivitamínico en la neuropatía óptica hereditaria de Leber (NOHL). Método: Dos pacientes diagnosticados de NOHL, fueron tratados con idebenona, vitamina C y riboflavina durante un año. Ambos fueron evaluados clínicamente antes, durante y después del tratamiento. Resultado: Ninguno de los dos pacientes experimentó mejoría visual y ambos sufrieron afectación en el segundo ojo. Conclusiones: A pesar de casos publicados en la literatura de recuperación visual con idebenona en pacientes con NOHL, nuestra experiencia indica que este tratamiento no es efectivo para la enfermedad de Leber
Objective: To ascertain the efficacy of idebenone and multivitamin treatment in Lebers hereditary optic neuropathy (LHON). Method: Two patients diagnosed of unilateral LHON were treated with megadoses of idebenone, vitamin C and riboflavin for one year. They were examined clinically before, during and after treatment. Results: No improvement of visual function was observed. Despite the idebenone treatment, in both cases the second eye became involved. Conclusions: Despite previous reports of visual recovery with idebenone in patients with LHON, our experience shows that an effective treatment for Lebers disease remains to be found
Assuntos
Masculino , Feminino , Adulto , Humanos , Benzoquinonas/administração & dosagem , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/tratamento farmacológico , Atrofia Óptica Hereditária de Leber/complicações , Atrofia Óptica Hereditária de Leber/diagnóstico , Atrofia Óptica/complicações , Atrofia Óptica/diagnóstico , Riboflavina/uso terapêutico , Quimioterapia Combinada , Benzoquinonas/uso terapêutico , Atrofia Óptica Hereditária de Leber/tratamento farmacológico , Ácido Ascórbico/uso terapêutico , Atrofia Óptica/tratamento farmacológico , Atrofia Óptica/epidemiologia , Atrofia Óptica/fisiopatologiaRESUMO
BACKGROUND: We present a case of Leber's hereditary optic neuropathy (LHON) manifested by malnutrition, tobacco and alcohol abuse. HISTORY AND SIGNS: We report on a 36-year-old patient with alcohol and tobacco abuse for years. 5 months before manifestation of LHON, the alcohol abuse was stopped. Because of congenital cataract the reduction in visual acuity, which occurred after alcohol consumption was stopped, was first misinterpreted. Findings at first exam: visual acuity right eye 0.2, left eye 0.05, temporal optic disc pallor left > right, vitamin B12 and folic acid at the lower level. Molecular genetic analysis: LHON mtDNA 11 778 mutation. Therefore, a pure tobacco-alcohol optic neuropathy could be excluded. THERAPY AND OUTCOME: Under high-dose vitamin-B complex substitution the visual acuity did not improve in the next 6 months. CONCLUSIONS: The cause of the manifestation of the LHON is unknown and multifactorial. In this case the manifestation was caused by malnutrition and tobacco abuse.
Assuntos
Alcoolismo/complicações , Desnutrição/complicações , Atrofia Óptica Hereditária de Leber/diagnóstico , Atrofia Óptica Hereditária de Leber/etiologia , Transtornos da Visão/etiologia , Adulto , Alcoolismo/diagnóstico , Diagnóstico Diferencial , Erros de Diagnóstico , Humanos , Masculino , Desnutrição/diagnóstico , Transtornos da Visão/diagnósticoRESUMO
We report three members of one family, a mother and two daughters aged 4 and 7 years, who developed visual loss from Leber hereditary optic neuropathy within a 19-month period. All three had been exposed to smoke from two large rubber tire fires within the previous 24 months, suggesting the possibility of an epigenetic triggering factor.