RESUMO
PURPOSE: This case report explores the role of the visual field perimetry and electroretinogram (ERG) in cases of non-infectious uveitis in the assessment and monitoring of retinal function and response to treatment. METHODS: A 59-year-old Caucasian female presenting with bilateral posterior uveitis newly diagnosed as birdshot chorioretinopathy (BSCR) presenting with bilateral decrease in visual acuity and cystoid macular edema, as well as a paracentral scotoma in the right eye. The diagnosis and follow-up of the case was done using visual field perimetry, optical coherence tomography (OCT), and ERG. RESULTS: Baseline ERG showed a marked decrease in the amplitudes of the scotopic and photopic responses and a delay of peak times mainly in the right eye. Mycophenolate mofetil at 2 g/day and oral prednisolone at 1 g/kg/day were administered with gradual tapering of the corticosteroids. After 5 months, there was a noticeable improvement in the visual acuity, macular edema in OCT, and an obvious increase in the amplitudes of the ERG associated with a decrease in peak times, particularly in the 30 Hz photopic 3.0 Flicker of the right eye. CONCLUSION: This case report highlights the importance of the peak time and wave amplitudes of the 30 Hz photopic DA 3.0 Flicker as being a sensitive parameter in the diagnosis and follow-up of BSCR.
Assuntos
Coriorretinite/fisiopatologia , Campos Visuais/fisiologia , Coriorretinopatia de Birdshot , Diagnóstico Diferencial , Eletrorretinografia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Retina/fisiopatologia , Escotoma/fisiopatologia , Tomografia de Coerência Óptica/métodos , Uveíte Posterior/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo VisualRESUMO
Fixational eye movements in 60 eyes of 30 patients with ABCA4-associated Stargardt disease were recorded by a Scanning Laser Ophthalmoscope (SLO). The results were quantified by two new fixation quality measures expressing the eccentricity of the preferred retinal locus (PRL) non-parametrically, and fixation stability by a dynamic index. 46 eyes (77%) fixated eccentrically; in 32 eyes (70% of the eccentrically fixating eyes) the PRL was located above the central retinal lesion. PRL eccentricity correlated positively with logMAR visual acuity (r=.72; p<.0001) and negatively with fixation stability (r=-.58; p<.0001). Multiple PRL were found only in three eyes.
Assuntos
Fixação Ocular , Degeneração Retiniana/fisiopatologia , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Movimentos Oculares , Feminino , Fóvea Central/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oftalmoscopia , Disco Óptico/patologia , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Acuidade VisualRESUMO
Mutations in the genes encoding the CNGA3 and CNGB3 subunits of the cyclic nucleotide-gated (CNG) channel of cone photoreceptors have been associated with autosomal recessive achromatopsia. Here we analyze the molecular basis of achromatopsia in two siblings with residual cone function. Psychophysical and electroretinographic analyses show that the light sensitivity of the cone system is lowered, and the signal transfer from cones to secondary neurons is perturbed. Both siblings carry two mutant CNGA3 alleles that give rise to channel subunits with different single-amino acid substitutions. Heterologous expression revealed that only one mutant forms functional channels, albeit with grossly altered properties, including changes in Ca2+ blockage and permeation. Surprisingly, coexpression of this mutant subunit with CNGB3 rescues the channel phenotype, except for the Ca2+ interaction. We argue that these alterations are responsible for the perturbations in light sensitivity and synaptic transmission.
Assuntos
Defeitos da Visão Cromática/genética , Canais Iônicos/genética , Adolescente , Adulto , Sequência de Aminoácidos , Cálcio/metabolismo , Linhagem Celular , Células Cultivadas , Defeitos da Visão Cromática/diagnóstico , Defeitos da Visão Cromática/fisiopatologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Análise Mutacional de DNA , Eletrorretinografia , Feminino , Predisposição Genética para Doença , Humanos , Canais Iônicos/metabolismo , Dados de Sequência Molecular , Mutação , Técnicas de Patch-Clamp , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Alinhamento de SequênciaRESUMO
We evaluated the function of the inner retina in patients with congenital stationary night blindness of the complete (CSNB1) and the incomplete type (CSNB2) by recording multifocal oscillatory potentials (mf-OPs). The VERIS system was used to record mf-OPs from 61 areas of the central retina from 5 CSNB1 patients (4 with NYX gene mutation), 6 CSNB2 patients (2 with CACNA1F mutation) and 11 control subjects. For each subject group, the first- and second-order kernel responses for one eye were analysed and the amplitudes and implicit times of their major components compared to 5 concentric rings centred on the fovea. In CSNB1 patients, the mf-OP peak amplitudes of the first-order kernel responses showed a significant reduction of the first peak without significant reduction of the second, whereas in CSNB2 both peak amplitudes were barely discernable from noise for all eccentricities. In the second-order kernel, the third peak was reduced in CSNB1 patients, and again not discernable from noise in CSNB2 patients. The difference in amplitude between the control and CSNB1 groups was significant for the late components of the first- and the second-order kernel. Implicit times were not significantly altered. The difference in mf-OP amplitude between CSNB1 and CSNB2 patients reflects the different molecular mechanisms underlying the two types of disease, which differentially affect the postreceptoral pathways of cone signal processing. The well-preserved peak 2 amplitudes of first-order mf-OPs and peak 3 amplitudes of second-order mf-OPs in CSNB1 patients point to a major impact of OFF-pathway components on these responses which are not present in CSNB2 patients. In conclusion, our results show that CSNB1 and CSNB2 are two different types of disease, not only on a genetic but also on a pathophysiological level.
Assuntos
Cegueira Noturna/congênito , Cegueira Noturna/fisiopatologia , Retina/fisiopatologia , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Cegueira Noturna/classificação , Cegueira Noturna/genéticaRESUMO
PURPOSE: To report the clinical, electrophysiological, and immunological features of a patient with X-linked hyper-IgM immunodeficiency syndrome type 1 (HIGM1) accompanied by a novel type of autoimmune retinopathy, including retinal pigment epithelium (RPE) hypersensitivity. METHODS: Comprehensive ophthalmological examinations, electrophysiological function testing, and inquiries into the immunological status of a 13-year-old presenting with subacute loss of vision in association with a molecularly confirmed diagnosis of HIGM1 were performed. The patient was genotyped by a PCR-based sequence tag content mapping strategy to define the genetic defect within the causative X-HIM gene TNFSF5. Since conventional allogenic bone marrow transplantation has been reported to cure HIGM1, a peripheral blood stem-cell transplantation was performed. RESULTS: (1) The patient's reduced visual acuity included prolonged dark adaptation and visual field constriction. Electrophysiology revealed a 'negative ERG' indicating post-receptoral dysfunction. (2) Initial immunological examination of the patient's serum identified abnormal antibody activity with components of the photoreceptors and the inner nuclear layer. The patient later developed indications of RPE hypersensitivity. A massively reduced light-peak to dark-trough ratio of the EOG slow oscillations (L/D ratio) corresponded to impaired RPE-photoreceptor complex function. (3) Molecular genetic analyses revealed the patient to be nullizygous for the tumor necrosis factor ligand member 5 gene (TNFSF5; CD40LG). A large chromosomal deletion of approximately 27.6-32.3 kb in size was identified in Xq26. (4) The transplant with its associated immunomodulation appeared to worsen rather than improve the patient's condition. CONCLUSIONS: The fundus appearance and electrophysiological function testing revealed indications of atypical retinal degeneration. However, the clinical course and the serological findings were consistent with those of ocular autoimmunity involving both antiretinal activity and RPE hypersensitivity. In this case, peripheral stem-cell transfusion with its associated chemotherapy failed to benefit the patient's vision; indications of autoimmunity appeared to increase following this treatment.
Assuntos
Doenças Autoimunes/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Hipergamaglobulinemia/imunologia , Síndromes de Imunodeficiência/imunologia , Epitélio Pigmentado Ocular/imunologia , Doenças Retinianas/imunologia , Adolescente , Chaperoninas , Eletrorretinografia , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Masculino , Mutação , Reação em Cadeia da Polimerase , Proteínas/genética , Doenças Retinianas/diagnóstico , Acuidade Visual , Campos VisuaisRESUMO
PURPOSE: To investigate the slow and fast rod signals of the scotopic 15-Hz flicker ERG in patients with molecularly confirmed Stargardt disease type I (STGD1). There is evidence that these slow and the fast rod ERG signals can be attributed to the rod bipolar-AII cell pathway and the rod-cone coupling pathway, respectively. METHODS: Twenty-seven patients with STGD1 with mutations in both alleles of the ABCA4 gene were included. Scotopic ERG response amplitudes and phases to flicker intensities ranging from -3.37 to -0.57 log scotopic troland x sec (log scot td x sec) were measured at a flicker frequency of 15 Hz. In addition, scotopic standard ERGs were obtained. Twenty-two normal subjects served as controls. RESULTS: The amplitudes of both the slow and fast rod ERG signals were significantly reduced in the STGD1 group. The phases of the slow rod signals lagged significantly, whereas those of the fast rod signals did not. The standard scotopic ERG did not reveal significant alterations. CONCLUSIONS: The results provide evidence that a defective ABCA4 transporter can functionally affect both the rod bipolar-AII cell pathway and the rod-cone coupling pathway. In STGD1, the scotopic 15-Hz flicker ERG may reveal subtle abnormalities at different sites within the rod system that remain undetected by standard ERG techniques.
Assuntos
Degeneração Macular/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/fisiopatologia , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Análise Mutacional de DNA , Adaptação à Escuridão , Eletrorretinografia , Feminino , Fusão Flicker , Humanos , Degeneração Macular/genética , Masculino , Pessoa de Meia-Idade , Estimulação LuminosaRESUMO
PURPOSE: A comprehensive screening was conducted for RP2 and retinitis pigmentosa GTPase regulator (RPGR) gene mutations including RPGR exon ORF15 in 58 index patients. The frequency of RPGR mutations was assessed in families with definite X-linked recessive disease (xlRP), and a strategy for analyzing the highly repetitive mutational hot spot in exon ORF15 is provided. METHODS: Fifty-eight apparently unrelated index-patients were screened for mutations in all coding exons of the RP2 and the RPGR genes, including splice-sites, by single-strand conformation polymorphism (SSCP) analysis, except for RPGR exon ORF15. A strategy for directly sequencing the large repetitive stretch of exon ORF15 from a 1.6-kb PCR-product was developed. According to pedigree size and evidence for X linkage, families were subdivided into three categories. RESULTS: Screening of 58 xlRP families revealed RP2 mutations in 8% and RPGR mutations in 71% of families with definite X-linked inheritance. Mutations clustered within a approximately 500-bp stretch in exon ORF15. In-frame sequence alterations in exon ORF15 ranged from the deletion of 36 bp to the insertion of 75 bp. CONCLUSIONS: Mutations in the RPGR gene are estimated to cause 15% to 20% of all cases of RP, higher than any other single RP locus. This report provides a detailed strategy to analyze the mutational hot spot in RPGR exon ORF15, which cannot be screened by standard procedures. The discrepancy of the proportion of families linked to the RP3 locus and those having RPGR mutations is resolved in a subset of families with definite X linkage.
Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos X/genética , Proteínas do Olho , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Retinose Pigmentar/genética , Análise Mutacional de DNA , Éxons/genética , Proteínas de Ligação ao GTP , Ligação Genética , Testes Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana , Fases de Leitura Aberta/genética , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteínas/genética , Análise de Sequência de DNARESUMO
PURPOSE: To describe a French family with the incomplete type of X-linked congenital stationary night blindness (CSNB2) associated with a novel mutation in the retina-specific calcium channel alpha(1) subunit gene (CACNA1F). DESIGN: Interventional case report. METHODS: Two family members with a history of nonprogressive night blindness and subnormal visual acuity were clinically examined and the genotype determined by molecular genetic analysis. RESULT: Both patients had clinical manifestations characteristic of CSNB2. Electrophysiologically, we found a predominant reduction of the ERG B-wave in the maximal response. Both rod and cone function were subnormal, with the latter tending to be more attenuated. We identified a C deletion at nucleotide position 4548, resulting in a frameshift with a predicted premature termination at codon 1524. CONCLUSIONS: The clinical and genetic study of a novel mutation in the CACNA1F gene adds further support to the contention that CSNB2 represents a genetically distinct retinal disorder of a calcium channel.
Assuntos
Canais de Cálcio Tipo L , Canais de Cálcio/genética , Mutação da Fase de Leitura , Doenças Genéticas Ligadas ao Cromossomo X/genética , Cegueira Noturna/genética , Canais de Cálcio/metabolismo , Cromossomos Humanos X/genética , Eletrorretinografia , França , Deleção de Genes , Ligação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Cegueira Noturna/congênito , Cegueira Noturna/fisiopatologia , Linhagem , Células Fotorreceptoras de Vertebrados/fisiologia , Acuidade VisualRESUMO
We investigated abnormalities of the retinal cone ON- and OFF-pathways in 24 males with Schubert-Bornschein congenital stationary night blindness (CSNB). Substantial differences were found between both CSNB types. In incomplete type, a-, b- and d-waves were reduced and delayed, whereas in complete type only the b-wave showed significant changes. Oscillatory potentials (OPs) were not discernible from noise in incomplete CSNB and showed significant peak alterations of the ON-OPs only in complete CSNB. In the complete CSNB type, the ON pathway appeared to be mainly affected. In the incomplete CSNB form marked involvement of both the ON and the OFF pathways was noted.
Assuntos
Eletrorretinografia , Cegueira Noturna/congênito , Adolescente , Adulto , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Cegueira Noturna/genética , Cegueira Noturna/fisiopatologia , Estimulação Luminosa/métodos , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Cromossomo XRESUMO
CASE REPORT: We report on a 37-year old patient with sudden onset of pain of the right scalp and an ipsilateral small pupil, presenting five weeks after chiropractic manipulation of the neck. METHODS/RESULTS: Pharmacologic pupil testing showed a postganglionic Horner's syndrome on the right side. Magnetic resonance angiography confirmed the diagnosis of a dissection of the right internal carotid artery at a subacute stage. CONCLUSION: There appears to be a causal relationship between carotid artery dissection and the chiropractic manipulation of the cervical spine. Ophthalmological signs played the key role in detecting this complication.
Assuntos
Dissecação da Artéria Carótida Interna/etiologia , Síndrome de Horner/etiologia , Manipulação Quiroprática/efeitos adversos , Adulto , Dissecação da Artéria Carótida Interna/diagnóstico , Diagnóstico Diferencial , Síndrome de Horner/diagnóstico , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , MasculinoRESUMO
PURPOSE: We investigated functional, morphological and electrophysiological changes in patients under anti-epileptic therapy with vigabatrin (VGB), a GABA aminotransferase inhibitor. METHODS: 20 epileptic patients treated with vigabatrin (age range 25-66 years) were enrolled in this study. The referrals were made by the treating neurologist, based on suspected or known visual field changes in these patients. Two patients had vigabatrin monotherapy, 18 patients were treated with vigabatrin in combination with other antiepileptic drugs. None of the patients reported visual complaints. Patients were examined with psychophysical tests including colour vision (Farnsworth D15), dark adaptation threshold, Goldmann visual fields and Tuebingen Automated Perimetry (90 degrees). A Ganzfeld ERG and an EOG following the ISCEV standard protocol were also obtained. Additionally, all patients were examined with the VERIS multifocal ERG including recordings of multifocal oscillatory potentials. RESULTS: Visual acuity, anterior and posterior segments, colour vision and dark adaptation thresholds were normal in all patients. Of 20 patients, 18 presented visual field constriction. All patients with visual field defects revealed altered oscillatory potentials waveforms in the ERG, especially in those patients with marked visual field defects. Multifocal oscillatory potentials were also delayed in those patients. In some patients a delayed cone single flash response (6/20), a reduced mERG amplitude (12/20) and a reduced Arden ratio (9/20) were found. CONCLUSIONS: The present data indicate an effect of vigabatrin on the inner retinal layers. Since abnormalities of the oscillatory potentials were seen in all patients with visual field defects a dysfunction of GABA-ergic retinal cell transmission might be assumed.
Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Retina/efeitos dos fármacos , Retina/fisiopatologia , Vigabatrina/efeitos adversos , Campos Visuais/efeitos dos fármacos , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada , Eletroculografia , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigabatrina/uso terapêuticoRESUMO
PURPOSE: To describe the clinical phenotype of the complete type of X-linked congenital stationary night blindness (CSNB1) with different types of mutations in the NYX gene. METHODS: The clinical and genetic data from 18 male patients with eight different mutations from two ophthalmological institutes were reviewed. The variability in refractive error, reduced visual acuity and full-field electroretinogram (ERG) recordings was examined. RESULTS: Parameters were quantitatively analyzed based on the classification of mutations according to their predicted effect on protein structure and function. CSNB1 patients with mutations changing structurally conserved residues ( n=12) tended to have a lower degree of myopia than patients with mutations of non-conserved residues ( n=6). Visual acuity loss and the 30 Hz flicker ERG recordings were similar in the two groups. Values for the b/a amplitude ratio tended to be clustered in patients carrying the same mutation. Refractive error and the b/a amplitude ratio were highly correlated between the two eyes of an individual. CONCLUSIONS: These data suggest correlations between phenotypic expression in CSNB1 and individual genotypes as well as class types of mutations based on the extent of structural amino acid conservation. A high inter-eye correlation suggests that other genetic or environmental factors, rather than chance, play a part in determining the phenotypic diversity in CSNB1.