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1.
Am J Ophthalmol ; 262: 114-124, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38278202

RESUMO

PURPOSE: Heterozygous mutations in the AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated with isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DESIGN: Cross-sectional study. METHODS: The following neuro-ophthalmological parameters were collected: logMAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness on optical coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and sex-matched group of OPA1 patients with a 1:2 ratio. All eyes were analyzed using a clustered Wilcoxon rank sum test with the Rosner-Glynn-Lee method. RESULTS: A total of 44 eyes from 23 ACO2 patients and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (P = .029, P = .023), average thickness (P = .012, P = .0007), and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. CONCLUSIONS: Clinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems to be associated with an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and is virtually indistinguishable from classic OPA1-DOA.


Assuntos
ATPases Associadas a Diversas Atividades Celulares , Aconitato Hidratase , GTP Fosfo-Hidrolases , Atrofia Óptica Autossômica Dominante , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Acuidade Visual , Campos Visuais , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Aconitato Hidratase/genética , Proteases Dependentes de ATP/genética , Proteases Dependentes de ATP/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Estudos Transversais , Estudos de Associação Genética , GTP Fosfo-Hidrolases/genética , Proteínas Mitocondriais/genética , Mutação , Fibras Nervosas/patologia , Atrofia Óptica Autossômica Dominante/genética , Atrofia Óptica Autossômica Dominante/fisiopatologia , Atrofia Óptica Autossômica Dominante/diagnóstico , Fenótipo , Células Ganglionares da Retina/patologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia
2.
Adv Ther ; 38(1): 278-289, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098555

RESUMO

INTRODUCTION: Joubert syndrome (JS) is a recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including optic nerve morphologic abnormalities. The function of the visual pathways, including the optic nerve, can be objectively evaluated by visual evoked potential (VEP) recordings. Our work aims to employ VEP to evaluate the neural conduction along the visual pathways in JS patients with or without optic nerve morphologic abnormalities (ONMA). METHODS: In this observational and prospective study, 18 children with genetic diagnosis of JS (mean age 8.78 ± 5.87 years) and 17 healthy age-similar control subjects (control group, 9.05 ± 6.02 years) were enrolled. Based on presence/absence of ONMA at fundus examination, JS patients were divided into two groups: the JS-A group (eight patients with ONMA) and JS-N group (ten patients without ONMA). Following the ISCEV standards, pattern VEPs were recorded in patients and controls in response to 60' and 15' checks to obtain a prevalent activation of large or small axons, respectively. RESULTS: Compared to controls, both the JS-A and JS-N groups showed significant abnormalities in 60' and 15' VEP implicit time and amplitude. Only in the JS-N group were values of 15' VEP implicit significantly correlated with the corresponding values of visual acuity. CONCLUSIONS: Our results suggest that a visual pathways dysfunction (of both large and small axons) detectable by VEP may occur in JS patients regardless of the presence of ONMA. Since clinical trials are envisaged in the near future to address JS-related ocular problems, our results might provide information about the potential usefulness of VEP recordings to assess the efficacy of treatments targeted to improve the visual pathways' function.


Assuntos
Anormalidades Múltiplas , Anormalidades do Olho , Doenças Renais Císticas , Adolescente , Cerebelo/anormalidades , Criança , Pré-Escolar , Eletrorretinografia , Potenciais Evocados Visuais , Anormalidades do Olho/diagnóstico , Humanos , Doenças Renais Císticas/diagnóstico , Estudos Prospectivos , Retina/anormalidades , Vias Visuais
3.
Adv Ther ; 37(9): 3827-3838, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32671685

RESUMO

INTRODUCTION: Joubert syndrome (JS) is an autosomal recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including congenital retinal dystrophy. The function of different retinal elements (rod, cone, bipolar cells) can be objectively evaluated by electroretinogram (ERG) recordings. Our work aims to evaluate the retinal function (by ERG recordings) in patients with JS with or without congenital retinal dystrophy. In addition, since clinical trials should be performed in the near future in JS, our results could provide information about the possible usefulness of ERG recordings in the assessment of the efficacy of treatments targeted to improve the retinal involvement. METHODS: In this observational and prospective study, 24 children with genetic identification for JS (mean age 10.75 ± 6.59 years) and 25 healthy age-similar normal control subjects (control group, mean age 10.55 ± 3.76 years) were enrolled. On the basis of the presence/absence of retinal dystrophy at fundus examination, patients with JS were divided into two groups: patients with JS with retinal dystrophy (16 children, mean age 11.00 ± 6.74 years, providing 16 eyes; JS-RD group) and patients with JS without retinal dystrophy (8 children, mean age 10.50 ± 6.45 years, providing 8 eyes; JS-NRD group). In patients with JS and controls, visual acuity (VA), dark-adapted, light-adapted, and 30-Hz flicker ERGs were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. RESULTS: When compared to controls, patients in the JS-RD and JS-NRD groups showed significant abnormalities of the values of dark-adapted, light-adapted, and 30-Hz flicker ERG parameters. The ERG and VA changes were not significantly correlated. CONCLUSIONS: Our results suggest that a dysfunction of photoreceptors and bipolar cells occurs in patients with JS with or without retinal dystrophy. The retinal impairment can be detected by ERG recordings and this method should be proposed to evaluate the effectiveness of adequate treatment targeted to improve the retinal impairment in patients with JS.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/fisiopatologia , Cerebelo/anormalidades , Eletrorretinografia/métodos , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/fisiopatologia , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/fisiopatologia , Retina/anormalidades , Retina/fisiopatologia , Acuidade Visual/fisiologia , Adolescente , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Itália , Masculino , Estudos Prospectivos
4.
Adv Ther ; 37(1): 566-577, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31828609

RESUMO

INTRODUCTION: This study aimed to evaluate whether the preoperative integrity of the inner segment (IS) and outer segment (OS) photoreceptoral junction may influence the postoperative visual acuity, the macular morphology [assessed by spectral domain optical coherence tomography (SD-OCT)], and macular function (evaluated by multifocal electroretinogram, mfERG) in patients with idiopathic epimacular membrane (EMM) followed up for 6 months. METHODS: In this observational prospective study, 18 patients with EMM (mean age 72.5 ± 6.87 years) were enrolled. They were divided into two groups according to the preoperative integrity of the SD-OCT IS/OS junction: the EMM-I group with an intact IS/OS junction (11 patients, mean age 72.75 ± 3.49 years, providing 11 eyes) and the EMM-D group with a disrupted IS/OS junction (7 patients, mean age 70.86 ± 10.79 years, providing 7 eyes). For each enrolled patient, visual acuity (VA), mfERG, and SD-OCT were assessed at baseline (preoperative) and after 1, 3, and 6 months of follow-up after surgical treatment for EMM (pars plana vitrectomy with EMM removal and internal limiting membrane peeling). RESULTS: During the whole follow-up, VA was significantly increased in EMM-I eyes and unmodified in EMM-D eyes. In both groups, mfERG responses were not significantly different and not related to VA differences. In EMM-I eyes a significant reduction of central retinal thickness (CRT) was observed; however, it was not correlated with VA changes. In EMM-D eyes CTR was not significantly reduced, whereas macular volume was significantly reduced. These changes were significantly related to the corresponding differences in VA. CONCLUSIONS: Our results suggest that the preoperative evaluation of the integrity of the IS/OS junction is relevant for postoperative outcomes. The recovery in VA was higher in EMM-I eyes than in EMM-D eyes. Postoperative recovery was not associated with morphology of the outer retina (photoreceptor and outer nuclear layer) and the function of preganglionic elements.


Assuntos
Membrana Epirretiniana/cirurgia , Células Fotorreceptoras de Vertebrados/fisiologia , Acuidade Visual/fisiologia , Vitrectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Eletrorretinografia/métodos , Feminino , Humanos , Masculino , Projetos Piloto , Período Pós-Operatório , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos
5.
Graefes Arch Clin Exp Ophthalmol ; 255(12): 2481-2486, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28831547

RESUMO

PURPOSE: To assess whether infantile visual deprivation induced by developmental cataract may influence the cone-driven retinal function in humans. METHODS: A total of 14 patients with history of bilateral developmental cataract (DC), who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity measurement. Light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function, respectively. RESULT: Mean values of light-adapted ERG a- and b-wave implicit times were slightly delayed when compared to HS values. Light-adapted ERG a-wave amplitude mean values showed borderline values (p = 0.001), whereas a-wave amplitude analysis at 5 ms, b-wave and PhNR amplitude mean values showed no significant differences when compared to control values. No significant correlations were found when age at surgery, time elapsed from surgery, duration of the visual deprivation, age at examination, age at first detection of the opacity, BCVA and electrophysiological parameters were plotted together. Coherently with morphological studies, the extremely light bioelectrical impairment of the cone pathway in our cohort of patients describes minimal functional abnormalities of a well-structured retina that is not completely mature. CONCLUSIONS: Our present results, combined to those of our previous work on congenital cataracts, allow us to enhance the comprehension of functional developmental mechanisms of children's retinas and highlight the relevance of the timely treatment of lens opacities during infancy.


Assuntos
Catarata/fisiopatologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Acuidade Visual , Adolescente , Catarata/congênito , Extração de Catarata , Criança , Pré-Escolar , Visão de Cores , Eletrorretinografia , Feminino , Seguimentos , Humanos , Masculino , Estimulação Luminosa , Células Ganglionares da Retina/fisiologia , Privação Sensorial , Fatores de Tempo , Adulto Jovem
6.
Acta Ophthalmol ; 95(2): 133-139, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27535202

RESUMO

PURPOSE: To assess whether the early light deprivation induced by congenital cataract may influence the cone-driven retinal function in humans. METHODS: Forty-one patients affected by congenital cataract (CC) who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity (BCVA) measurement; light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function respectively. RESULTS: Mean values of light-adapted ERG a- and b-wave and PhNR amplitude of CC eyes were significantly reduced and photopic ERG b-wave implicit time mean values were significantly delayed when compared to HS ones. When studying photopic ERG mean amplitudes at 5 ms, significant differences were found when comparing CC and control eyes. In CC eyes, statistically significant correlations were found between a- and b- wave amplitudes and PhNR amplitudes. No significant correlations were found between ERG parameters and BCVA, as well as between the age of CC patients at surgery and the time elapsed from lens extraction. No significant differences were found when functional parameters of bilateral and unilateral congenital cataract (uCC) eyes were compared, however uCC eyes showed significant differences when compared with contralateral healthy eyes. CONCLUSION: We found a significant impairment of cone-driven retinal responses in patients with a history of congenital cataract. These changes might result from the long-lasting effects of early light deprivation on the cone retinal pathways. Our findings support the relevance of retinal involvement in deficits induced by early light deprivation.


Assuntos
Catarata/terapia , Visão de Cores/fisiologia , Eletrorretinografia/métodos , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/fisiologia , Privação Sensorial , Acuidade Visual/fisiologia , Adolescente , Catarata/congênito , Catarata/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estimulação Luminosa , Campos Visuais
7.
PLoS One ; 10(6): e0127906, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26047507

RESUMO

PURPOSE: To investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON). METHODS: All patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections. RESULTS: MM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7µm vs 122.3±9µm in MM patients (p<0.01) and 128.5±8µm vs. 122.3±9µm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mµ) compared to patients without MM [77.5±8mµ (p<0.001)] and controls [78.4±7mµ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls. CONCLUSION: The prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces.


Assuntos
Atrofia Óptica Hereditária de Leber/patologia , Retina/fisiopatologia , Adulto , Algoritmos , Estudos de Casos e Controles , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/fisiologia , Atrofia Óptica Autossômica Dominante/epidemiologia , Atrofia Óptica Autossômica Dominante/patologia , Atrofia Óptica Hereditária de Leber/epidemiologia , Nervo Óptico/fisiologia , Prevalência , Radiografia , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica , Acuidade Visual
8.
Doc Ophthalmol ; 127(3): 217-25, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23943132

RESUMO

PURPOSE: To explore functional retinal changes in neovascular AMD patients (nAMD) treated with ranibizumab 0.5 mg combined with photodynamic therapy (PDT) 3 days after the first injection in the long term. METHODS: Patients with no prior treatment for nAMD were treated with 3 injections of ranibizumab 0.5 mg 1 month apart and a single session of standard PDT 3 days after the first injection. Best-corrected visual acuity and time-domain OCT at baseline and every 28 ± 2 days were performed; microperimetry at 3, 6, and 12 months and multifocal electroretinogramm (mfERG) at 3 and 12 months were repeated. Fluorescein angiography and vision-related quality-of-life questionnaire were performed at baseline and 12 months. RESULTS: 12/15 nAMD patients completed the 12 months study and received an average of 3.4 ± 0.7 injections. Mean VA changed from 54.67 ± 15.72 to 59.0 ± 24.77 letters (p = 0.371), while mean retinal sensitivity from 5.5 ± 4.8 to 6.6 ± 6.0 dB (p = 0.216). MfERG N1-P1 response amplitude densities (RADs) were significantly different from baseline (p < 0.01) in the central 0°-2.5°, whereas in the peripheral retinal areas (2.5°-20°), not significant (p > 0.01) changes in N1-P1 RADs were detected. The "general vision" VFQ-25 subscale showed a statistically significant improvement at 3 and 12 months. CONCLUSIONS: Ranibizumab 0.5 mg combined with standard PDT 3 days after the first injection determines an improvement of mfERG values in the retinal central area in nAMD patients in long-term follow-up.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fotoquimioterapia , Retina/fisiopatologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/fisiopatologia , Idoso , Terapia Combinada , Eletrorretinografia , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Qualidade de Vida , Ranibizumab , Perfil de Impacto da Doença , Inquéritos e Questionários , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual , Degeneração Macular Exsudativa/diagnóstico
9.
Retina ; 32(8): 1531-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22614742

RESUMO

PURPOSE: To review prevalence, long-term progression, and prognosis of vitreoretinal interface modifications in pathologic myopia with posterior staphyloma and investigate foveal sensitivity and fixation stability. METHODS: Retrospective single-institution series of 214 eyes (116 patients) with pathologic myopia, axial length >30 mm, and posterior staphyloma. Exclusion criteria included follow-up less than five years, incomplete records, and/or less than three optical coherence tomography or microperimetry. Patients were divided into 5 groups according to optical coherence tomography: 1) epiretinal membrane without schisis (ERM); 2) macular retinal schisis (Schisis); 3) partial thickness macular hole (PTMH); 4) full-thickness macular hole (FTMH); and 5) posterior retinal detachment (PRD) with or without macular hole. Disease progression was defined as a visual acuity decrease of two or more lines associated to objective worsening of the optical coherence tomography and/or microperimetry. RESULTS: Vitreoretinal abnormalities at baseline were present in 116 of 204 patients (56.8%) and 214 of 408 eyes (52.4%); 98 of 116 patients (84.4%) showed bilateral involvement. Baseline visual acuity and foveal sensitivity varied significantly with ERM performing better and PRD worse than others; PTMH and FTMH did not differ. During the 66 months of average follow-up, 33 of 214 eyes (15.4%) required surgery and 13 of 33 eyes (39.3%) needed reintervention. Surgery rate significantly differed among groups: 2% for ERM, 20% to 25% for Schisis, PTMH, and FTMH, and up to 50% for PRD. Progression rate of Schisis and FTMH was the same, regardless of symptoms, while macula-off PRD always required surgery. Decrease of fixation stability and foveal sensitivity correlated to need for surgery, while baseline foveal sensitivity and fixation did not. CONCLUSION: Vitreoretinal interface pathology in pathologic myopia with posterior staphyloma encompasses a spectrum of conditions whose baseline functionality, prognosis, rate, and amount of progression vary significantly. Customized treatment for each different condition should be considered.


Assuntos
Membrana Epirretiniana/fisiopatologia , Miopia Degenerativa/fisiopatologia , Descolamento Retiniano/fisiopatologia , Perfurações Retinianas/fisiopatologia , Retinosquise/fisiopatologia , Corpo Vítreo/patologia , Adulto , Dilatação Patológica , Progressão da Doença , Membrana Epirretiniana/diagnóstico , Feminino , Fixação Ocular/fisiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segmento Posterior do Olho/patologia , Prevalência , Prognóstico , Descolamento Retiniano/diagnóstico , Perfurações Retinianas/diagnóstico , Retinosquise/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual
10.
Ophthalmic Surg Lasers Imaging ; 42(3): 209-15, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21410092

RESUMO

BACKGROUND AND OBJECTIVE: To evaluate the repeatability of optic nerve head (ONH) measurements by spectral-domain optical coherence tomography. PATIENTS AND METHODS: Three scans were acquired in 32 healthy subjects during one session. Using Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA), the cup-to-disc ratio (CDR), disc area, rim area, cup volume, and horizontal and vertical CDRs were investigated. Repeatability was assessed by the coefficient of variation (COV), the test-retest intrasession variability, and the intraclass correlation coefficient (ICC). RESULTS: Good repeatability was achieved for all parameters, with a COV of 4.23% or less and ICCs of 0.98 or greater for all measurements. Test-retest intrasession variability was 0.024 for CDR, 0.121 mm(2) for disc area, 0.087 mm(2) for rim area, 0.017 mm(3) for cup volume, and 0.048 for horizontal and vertical CDR. CONCLUSION: In healthy eyes, Cirrus HD-OCT provides repeatable measurements of ONH parameters.


Assuntos
Disco Óptico/anatomia & histologia , Tomografia de Coerência Óptica/instrumentação , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes
11.
Neurorehabil Neural Repair ; 25(6): 512-20, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21444653

RESUMO

BACKGROUND: To date, no specific therapy is available for optic glioma (OG)-induced visual loss. OBJECTIVE: To evaluate the effects on visual function of murine nerve growth factor (NGF) eye drop administration in children with severe visual impairment due to low-grade OGs. METHODS: Five patients with OGs and advanced optic nerve atrophy were assessed before and after a single 10-day course of 1 mg murine NGF topical administration by clinical evaluation, visual evoked potentials (VEPs), and brain magnetic resonance imaging (MRI). VEPs, the main functional outcome measure, were recorded at baseline and 1, 30, 45, 90, and 180 days posttreatment. MRI examinations were performed at baseline and at 180 days after NGF treatment. Six untreated control patients with OGs also underwent serial VEPs, clinical testing, and MRI assessments. RESULTS: After NGF treatment, median VEPs amplitude showed a progressive increase from the baseline values (P < .01). VEPs reached a maximum amplitude at 90 days (170% increase) and declined at 180 days, still remaining above the baseline level. Perception of spontaneous visual phosphenes was noted in all patients after NGF administration. MRI showed stable tumor size. In controls, clinical findings and VEPs did not show any significant change over the observation period. CONCLUSIONS: The findings from the study show that NGF administration may be an effective and safe adjunct therapy in children with optic atrophy due to OGs. The beneficial effect on optic nerve function suggests a visual rescuing mechanism exerted by murine NGF on the residual viable optic pathways.


Assuntos
Cegueira/tratamento farmacológico , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Glioma do Nervo Óptico/fisiopatologia , Nervo Óptico/efeitos dos fármacos , Administração Tópica , Adolescente , Animais , Cegueira/diagnóstico , Cegueira/etiologia , Cegueira/patologia , Criança , Pré-Escolar , Eletrodiagnóstico/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Camundongos , Fator de Crescimento Neural/efeitos adversos , Regeneração Nervosa/fisiologia , Nervo Óptico/patologia , Nervo Óptico/fisiopatologia , Glioma do Nervo Óptico/complicações , Glioma do Nervo Óptico/diagnóstico , Projetos Piloto , Vias Visuais/efeitos dos fármacos , Vias Visuais/patologia , Vias Visuais/fisiopatologia
12.
J Glaucoma ; 20(2): 100-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20436364

RESUMO

PURPOSE: Elevated intraocular pressure is a crucial pathologic event for the development of glaucoma (GL). We have reported that nerve growth factor (NGF) reaches retinal cells and the optic nerve (ON) when applied to the eye. Whether ocular application of NGF prevents or reduces damage to retinal ganglion cell (RGC) is not known. METHODS: GL was induced in adult rats by the injection of hypertonic saline into the episcleral vein of the right eye and the left eye used as control. Rats were then treated daily with ocular application of NGF or vehicle solution for 7 weeks. Retinal and ON tissues were then used for structural, immunohistochemical, and biochemical studies. RESULTS: The injection of hypertonic saline into the episcleral vein led to progressive degeneration of RGCs, with the loss of nearly 40% of these cells after 7 weeks of treatment. This cellular loss is associated with the downregulation of NGF and NGF-receptor expression in the retina and ON of the glaucomatous eye and ocular treatment with NGF significantly reduced the deficit induced by GL. CONCLUSIONS: These findings indicate that NGF can exert protective action on RGC degeneration occurring in glaucomatous retina. We suggest that ocular NGF treatment might be a suitable pharmacologic approach to investigate protective mechanisms of degenerating RGCs.


Assuntos
Modelos Animais de Doenças , Glaucoma/prevenção & controle , Fator de Crescimento Neural/administração & dosagem , Degeneração Retiniana/prevenção & controle , Células Ganglionares da Retina/efeitos dos fármacos , Administração Tópica , Animais , Western Blotting , Contagem de Células , Glaucoma/metabolismo , Glaucoma/patologia , Imuno-Histoquímica , Pressão Intraocular , Masculino , Degeneração Neural , Soluções Oftálmicas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Tonometria Ocular
13.
Vision Res ; 49(1): 54-63, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18938194

RESUMO

We investigated the effect of glaucoma (GL) on nerve growth factor (NGF) presence in two brain visual areas. Rats with elevated intraocular pressure (EIOP), induced by hypertonic saline injection in the episcleral vein, were treated with eye topical application of saline or NGF. Rats were subsequently sacrificed, and brain tissues were used for immunohistochemical, biochemical, and molecular analyses. We found that GL alters the basal level of NGF and NGF receptors in brain visual centers and that NGF eye application normalized these deficits. These findings demonstrate that the reduced presence of NGF can arise due to degenerative events in retinal and brain visual areas.


Assuntos
Corpos Geniculados/metabolismo , Glaucoma/metabolismo , Fator de Crescimento Neural/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Córtex Visual/metabolismo , Administração Tópica , Animais , Western Blotting/métodos , Corpos Geniculados/química , Imuno-Histoquímica , Masculino , Modelos Animais , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor trkA/análise , Receptor trkA/metabolismo , Receptores de Fator de Crescimento Neural/análise , Córtex Visual/química
14.
Eur J Neurosci ; 25(9): 2741-54, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17459106

RESUMO

Elevated intraocular pressure may lead to retinal ganglion cell injury and consequent visual deficits. Chronic intraocular pressure increase is a major risk factor for glaucoma, a leading blinding disease, and permanent visual deficits can also occur following acute pressure increments due to trauma, acute glaucoma or refractive surgery. How pressure affects retinal neurons is not firmly established. Mechanical damage at the optic nerve head, reduced blood supply, inflammation and cytotoxic factors have all been called into play. Reasoning that the analysis of retinal neurons soon after pressure elevation would provide useful cues, we imaged individual ganglion cells in isolated rat retinas before and after short hydrostatic pressure increments. We found that slowly rising pressure to peaks observed in trauma, acute glaucoma or refractive surgery (50-90 mmHg) did not damage ganglion cells, whereas a rapid 1 min pulse to 50 mmHg injured 30% of these cells within 1 h. The severity of damage and the number of affected cells increased with stronger or repeated insults. Degrading extracellular ATP or blocking the P2X receptors for ATP prevented acute pressure-induced damage in ganglion cells. Similar effects were observed in vivo. A short intraocular pressure transient increased extracellular ATP levels in the eye fluids and damaged ganglion cells within 1 h. Reducing extracellular ATP in the eye prevented damage to ganglion cells and accelerated recovery of their response to light. These data show that rapid pressure transients induce acute ganglion cell injury and unveil the causal role of extracellular ATP elevation in such injury.


Assuntos
Trifosfato de Adenosina/metabolismo , Líquido Extracelular/metabolismo , Glaucoma/complicações , Pressão Intraocular/fisiologia , Degeneração Retiniana/etiologia , Degeneração Retiniana/fisiopatologia , Células Ganglionares da Retina/metabolismo , Animais , Degeneração Neural/etiologia , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Disco Óptico/fisiopatologia , Técnicas de Cultura de Órgãos , Antagonistas do Receptor Purinérgico P2 , Ratos , Ratos Long-Evans , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2X , Degeneração Retiniana/metabolismo , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
15.
Retina ; 27(3): 312-20, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17460586

RESUMO

PURPOSE: To evaluate macular function before and after surgical peeling of idiopathic epimacular membrane (EMM). METHODS: Logarithm of the minimal angle of resolution visual acuity and results of focal (central 9 x 9 degrees) electroretinogram (fERG), pattern electroretinogram (pERG), and optical coherence tomography (OCT) assessment of macular volume were evaluated for 22 eyes of 22 patients (mean age +/- SD, 63.20 +/- 10.0 years) with EMM preoperatively (baseline) and 6 months after surgical peeling. Preoperative visual acuity and fERG and pERG amplitudes observed in EMM eyes were compared with those in 15 age-matched control eyes. RESULTS: In the preoperative evaluation, EMM eyes had a significant (P < 0.01; one-way analysis of variance) reduction in visual acuity and fERG and pERG amplitudes and an increase in OCT macular volume when compared with controls. In EMM eyes, the decrease in visual acuity was significantly correlated (P < 0.01, Pearson test) to the reduction in fERG and pERG amplitudes. At the postoperative evaluation, EMM eyes had a correlated significant (P < 0.01) increase in visual acuity, fERG amplitude, and pERG amplitude with respect to the preoperative values. All EMM eyes had a significant (P <0.01) reduction in macular volume, and retinal microanatomy was restored to normal conditions. CONCLUSION: In EMM eyes, the decrease in visual acuity is related to dysfunction of both preganglionic (abnormal fERG) and ganglionic (abnormal pERG) macular elements. Surgical removal of EMM may induce improvement of the function of both outer and innermost macular retinal layers, leading to a related increase in visual acuity.


Assuntos
Eletrorretinografia/métodos , Membrana Epirretiniana/fisiopatologia , Membrana Epirretiniana/cirurgia , Células Fotorreceptoras de Vertebrados/fisiologia , Células Ganglionares da Retina/fisiologia , Adulto , Idoso , Membrana Epirretiniana/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia
16.
Ophthalmology ; 114(4): 692-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17208303

RESUMO

OBJECTIVE: To evaluate possible changes of vitreous status in emmetropic eyes after uneventful phacoemulsification surgery, and possible related complications such as the onset of retinal detachment (RD). DESIGN: Retrospective case series. PARTICIPANTS: Four hundred fifty-three emmetropic eyes from 453 patients (mean age, 62.03+/-5.57 years) subjected to uneventful phacoemulsification with intraocular lens implantation in the capsular bag were considered in the study. They had a refractive error within +/-0.5 diopters (mean, -0.21+/-0.08). Eyes with peripheral retinal lattice degeneration were included only if asymptomatic and only if the degeneration involved one retinal quadrant. After cataract surgery, the 453 eyes were evaluated preoperatively at days 1, 15, and 30 and months 3, 6, 12, 18, 24, 36, 48, and 60. The whole period of follow-up was 5 years. METHODS: Evaluation of vitreous status by biomicroscopic examination, indirect binocular ophthalmoscopy, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Postoperative onset of posterior vitreous detachment (PVD) and RD. RESULTS: After cataract surgery, a PVD occurred in 107 of 141 (75.88%) eyes without preoperative PVD or lattice degeneration. Posterior vitreous detachment occurred in 41 of 47 eyes (87.23%) with preoperative lattice degeneration and no PVD. Eyes with preoperative lattice degeneration and postoperative PVD showed a higher incidence of RD after cataract surgery (21.27%) than eyes without preoperative PVD or lattice degeneration (0.70%). In all patients with lattice degeneration, RD originated from horseshoe retinal tears on lattice areas located on the superior quadrants. No correlation was observed between the development of RD and age. CONCLUSIONS: Our results suggest that the onset of postoperative PVD should be considered an important risk factor for the development of RD after cataract surgery, particularly in eyes with lattice areas.


Assuntos
Facoemulsificação , Complicações Pós-Operatórias , Descolamento Retiniano/etiologia , Descolamento do Vítreo/etiologia , Idoso , Biometria , Feminino , Humanos , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Degeneração Retiniana/complicações , Estudos Retrospectivos , Fatores de Risco , Acuidade Visual
17.
Ophthalmology ; 110(12): 2355-61, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14644718

RESUMO

PURPOSE: To evaluate the incidence of retinal detachment (RD) after cataract surgery performed by phacoemulsification in very highly myopic eyes. DESIGN: Retrospective, paired-eye, case-control trial. PARTICIPANTS AND INTERVENTION: We assessed the development of RD in 930 eyes from 930 subjects (mean age = 62.5 +/- 8.5 years) affected by very high myopia (between -15 and -30 diopters) undergoing cataract surgery after uncomplicated phacoemulsification (cataract-subjected [CS] eyes). Fellow eyes served as controls. Follow-up was 36 months. MAIN OUTCOME MEASURE: Detachment of the retina. RESULTS: Retinal detachment was observed in 8.0% of CS eyes compared with 1.2% of control eyes (P<0.01, chi-square test). In CS eyes, posterior RD was most common (52.7% of eyes with RD). In control eyes, peripheral detachments with or without macular involvement were most common (47.3% of eyes with RD). CONCLUSION: Cataract surgery, despite the use of a safe technique such as phacoemulsification, increases the risk of RD development in very highly myopic eyes.


Assuntos
Miopia/complicações , Facoemulsificação/efeitos adversos , Descolamento Retiniano/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Capsulorrexe , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acuidade Visual
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