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1.
Eur J Ophthalmol ; 29(1_suppl): 27-31, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31282209

RESUMO

PURPOSE: To describe the diagnostic complexities of a patient with acute zonal occult outer retinopathy. CASE REPORT: A healthy female presented with acute bilateral visual field loss and photopsia. On initial examination, her visual acuity, colour vision, fundus examination and fluorescein angiography were normal. Fundus autofluorescence, however, revealed scattered hyperautofluorescence in both eyes and electrodiagnostic tests were abnormal. A differential diagnosis including acute zonal occult outer retinopathy was postulated and serology requested. The patient's past medical history included both breast and endometrial cancer and raised the possibility of cancer-associated retinopathy. A normal full-body positron emission tomography scan, negative antibodies for cancer-associated retinopathy and abnormal electroretinogram led to a diagnosis of acute zonal occult outer retinopathy. CONCLUSION: It has been more than 20 years since Gass first described the syndrome of acute zonal occult outer retinopathy. Typically affecting young, healthy females, acute zonal occult outer retinopathy is characterised by photopsia, minimal fundoscopic changes and electroretinographic abnormalities. Visual field loss is permanent and often associated with slow-progressing degeneration of the retinal pigment epithelial cells. Retinal photoreceptor dysfunction is an uncommon and unrecognised cause of acute visual loss. Acute zonal occult outer retinopathy should be considered as a differential diagnosis in those patients with deceptively normal fundal examinations, abnormal electroretinograms and visual field loss.


Assuntos
Retina/fisiopatologia , Escotoma/diagnóstico , Diagnóstico Diferencial , Eletrorretinografia , Feminino , Angiofluoresceinografia/métodos , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Retina/diagnóstico por imagem , Escotoma/tratamento farmacológico , Escotoma/fisiopatologia , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
2.
Doc Ophthalmol ; 139(2): 151-160, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31267413

RESUMO

PURPOSE: Usher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TREATRUSH). METHODS: A total of 268 genetically confirmed USH patients underwent electrophysiological examinations in the context of multimodal ophthalmological examination in the study (75 USH1, 189 USH2 and four USH3). Full-field electroretinography (ERG) was performed according to ISCEV standards, visual field determination was carried out with either the Octopus or Goldmann perimeters and visual acuity was examined with either ETDRS or Snellen charts. The data were compared between USH subtypes (USH1/USH2/USH3) and correlated with age. RESULTS: Visual acuity decreases significantly with age for both USH1 and USH2 (p < 0.001), without a difference between the two cohorts. When corrected for age, the preserved kinetic visual field was significantly larger in USH2 than in USH1 (p = 0.04). Furthermore, the preserved kinetic visual field area showed a significant decrease with age (based on an exponential fit) in both USH1 and USH2 (p < 0.001). In USH1 patients, however, the visual field was already vastly reduced at an early age. The ERG results were abnormal in all patients. Detectable data for scotopic ERG were obtained from nine patients, and data of photopic ERG were obtained from 24 patients, without a difference between USH1 and USH2 subtypes. CONCLUSIONS: There are differences in the phenotypes of RP in USH subtypes, most visible in the progression of visual fields between USH1 and USH2. The perimetric reduction occurs earlier in USH1 than in USH2. In both subtypes, visual acuity decreases significantly with age and the ERG is not detectable already at early ages.


Assuntos
Eletrorretinografia , Retinite Pigmentosa/fisiopatologia , Síndromes de Usher/fisiopatologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia , Adulto , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Retina/fisiopatologia , Retinite Pigmentosa/etnologia , Síndromes de Usher/etnologia , Testes de Campo Visual , Adulto Jovem
3.
BMC Ophthalmol ; 19(1): 129, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208350

RESUMO

BACKGROUND: To evaluate the retinal function before and soon after an intravitreal injection of an anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Seventy-nine eyes of 79 patients that were treated by an intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) with macular edema (ME) were studied. The RETeval® system was used to record 28 Hz flicker electroretinograms (ERGs) from the injected and non-injected eyes before (Phase 1, P1), within 2 h after the injection (P2), and 2 to 24 h after the injection (P3). Patients were grouped by disease or by the injected agent and compared. The significance of the changes in the implicit times and amplitudes was determined by t tests. RESULTS: The amplitudes were not significantly different at the three phases. The implicit time of the injected eye was 31.2 ± 3.2 msec at P1, and it was not significantly different at P2 (31.7 ± 3.1 msec) but it was significantly longer at P3 (32.2 ± 3.3 msec, P < 0.01, ANOVA for both). The implicit time in the non-injected fellow eye was 30.5 ± 3.3 msec at P1, and it was significantly longer at P2 (31.1 ± 3.2 msec) and phase 3 (31.3 ± 3.4 msec, P < 0.01, ANOVA for both). CONCLUSIONS: The results indicate that an intravitreal anti-VEGF injection will increase the implicit times not only in the injected eye but also in the non-injected eye soon after the intravitreal injection.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Retina/fisiopatologia , Oclusão da Veia Retiniana/tratamento farmacológico , Idoso , Análise de Variância , Retinopatia Diabética/tratamento farmacológico , Eletrorretinografia , Feminino , Humanos , Injeções Intravítreas , Degeneração Macular/fisiopatologia , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
4.
BMC Ophthalmol ; 19(1): 112, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31096936

RESUMO

BACKGROUND: Oxidative stress (OS) is an essential factor in the pathogenesis of branch retinal vein occlusion (BRVO). Studies have demonstrated the role of hydrogen gas in the regulation of OS. This study was designed to evaluate the efficacy of hydrogen gas on the BRVO rat model. METHODS: Twenty-four BRVO rats were randomly divided into two groups: the hydrogen gas (H) group (42% H2, 21% O2, 37% N2) and the model (M) group (21% O2, 79% N2). Rats in the H group inhaled hydrogen gas for 8 h every day up to 30 d post-occlusion. Twelve age-matched healthy rats served as the control (C) group. Retinal function and morphology were detected at 1, 7, 14 and 30 d post-occlusion. Furthermore, the expression of vascular endothelial growth factor (VEGF-α) was detected by immunofluorescent staining. RESULTS: Full-field electroretinography (ffERG) revealed that the amplitude of the b-wave (dark-adaptation 3.0 response), the amplitude of the OPs2 wave and the light-adapted flicker response in the H group were all higher than those in the M group at 7 d post-occlusion (all p < 0.05). The reopen time of occlusive retinal vessels in the H group was 2.235 ± 1.128 d, which was shorter than that in the M group (4.234 ± 2.236 d, p < 0.05). The rats in the H group had a thinner IPL + GCL + NFL and an increased total retina compared with those in the M group at 3 d post-occlusion (p < 0.05), while the rats in the H group had a thicker INL, IPL + GCL + NFL and total retina compared with those at 7, 14 and 30 d post-occlusion (p < 0.05). Moreover, the flow velocity of ear vein blood was increased in the H group compared with that in the M group (p < 0.05). The expression of VEGF-α in the H group was dramatically decreased compared with that in the M group at 1, 7 and 14 d post-occlusion (p < 0.05), while the expression kept in similar level at 30 d post-occlusion (p > 0.05). CONCLUSIONS: Our findings demonstrate that inhalation of hydrogen gas could alleviate retinal oedema, shorten reopen time and improve retinal function, and the potential mechanism might be related to a decrease in VEGF-α expression.


Assuntos
Hidrogênio/farmacologia , Retina/efeitos dos fármacos , Oclusão da Veia Retiniana/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Modelos Animais de Doenças , Eletrorretinografia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retina/metabolismo , Retina/fisiopatologia , Oclusão da Veia Retiniana/fisiopatologia
5.
Invest Ophthalmol Vis Sci ; 60(6): 2173-2180, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31108548

RESUMO

Purpose: Environmental light plays an important role in the process of emmetropization. This study investigated how the retina integrates wavelength and temporal signals to regulate eye emmetropization. Methods: Guinea pigs (n = 220) were randomly divided into 11 groups (n = 20/group) that received different environmental lighting (12:12 light cycle) for 8 weeks: white, green, or blue light at steady, 0.5 or 20 Hz. White-steady group was repeated for each wavelength. Refraction, axial length, and corneal curvature were measured using streak retinoscopy, A-scan ultrasonography, and keratometry, respectively, every 2 weeks. Results: (1) In white light, the white-0.5 Hz group was more myopic than the white-steady group or the white-20 Hz group (both P < 0.0001), with a longer axial length (both P < 0.0001). White-20 Hz did not significantly differ from white-steady. (2) At low temporal frequencies (0 and 0.5 Hz), green-steady (P = 0.0008) and green-0.5 Hz (P < 0.0001), were more myopic than the white-steady group, with longer axial lengths (both P < 0.0001). No significant difference was found between green-0.5 Hz and green-steady. Blue-steady and blue-0.5 Hz were more hyperopic than white-steady (both P < 0.0001), with shorter axial lengths (both P < 0.0001). Blue-0.5 Hz showed no significant difference from blue-steady. (3) At high temporal frequencies (20 Hz), green-20 Hz, was more hyperopic than green-steady or green-0.5 Hz (both P < 0.0001) and had a shorter axial length (both P < 0.0001). Green-20 Hz showed a 1.10 D hyperopic shift compared to green-steady. Blue-20 Hz was less hyperopic than blue-steady (P < 0.0001) or blue-0.5 Hz (P = 0.0012), with a longer axial length (both P < 0.0001). Blue-20 Hz showed a 1.18 D myopic shift compared to blue-steady. Conclusions: Eyes use both wavelength and temporal frequency of light to regulate emmetropization. Their interactions provide different cues to control eye growth. At low temporal frequencies, the eye can use wavelength defocus to guide eye growth. This signal is weakened at high temporal frequencies.


Assuntos
Adaptação Ocular/fisiologia , Emetropia/fisiologia , Luz , Refração Ocular/fisiologia , Erros de Refração/fisiopatologia , Animais , Animais Recém-Nascidos , Comprimento Axial do Olho/fisiologia , Modelos Animais de Doenças , Cobaias , Retina/fisiopatologia
6.
Invest Ophthalmol Vis Sci ; 60(6): 2049-2063, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074760

RESUMO

Purpose: To assess the phenotypic variability and natural course of inherited retinal diseases (IRDs) caused by EYS mutations. Methods: Multiethnic cohort study (N = 30) with biallelic EYS variants from a clinical IRD database (retinitis pigmentosa [RP], N = 27; cone-rod dystrophy [CRD], N = 1; and macular dystrophy, N = 2). In vitro minigene splice assay was performed to determine the effect on EYS pre-mRNA splicing of the c.1299+5_1299+8del variant in macular dystrophy patients. Results: We found 27 different EYS variants in RP patients and 7 were novel. The rate of visual field loss of the V4e isopter area was -0.84 ± 0.44 ln(deg2) per year, and the rate of visual acuity loss was 0.75 Early Treatment Diabetic Retinopathy Study letters per year. Ellipsoid zone width was correlated with area of the hyperautofluorescent ring, with rs = 0.78 and P < 0.001. Rate of decline in ellipsoid zone width was -57 ± 17 µm per year (P < 0.01) (n = 14) or -3.69% ± 0.51% from baseline per year (P < 0.001). An isolated CRD patient carried a homozygous EYS variant (c.9405T>A), previously identified in RP patients. Two siblings with macular dystrophy carried compound heterozygous EYS variants: c.1299+5_1299+8del and c.6050G>T. The former was novel and shown to result in skipping of exon 8, and the latter was a known RP variant. Conclusions: We report on EYS-associated macular dystrophy, extending the spectrum of EYS-associated IRDs. We observed heterogeneity between RP patients in age of onset and disease progression. Identical EYS variants were found in cases with RP, CRD, and macular dystrophy. Screening for EYS variants in CRD and macular dystrophy patients might increase the diagnostic yield in previously unsolved cases.


Assuntos
Proteínas do Olho/genética , Degeneração Macular/genética , Mutação , RNA Mensageiro/genética , Retina/patologia , Retinite Pigmentosa/genética , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Eletrorretinografia , Proteínas do Olho/metabolismo , Feminino , Homozigoto , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Retina/metabolismo , Retina/fisiopatologia , Retinite Pigmentosa/diagnóstico , Retinite Pigmentosa/metabolismo , Tomografia de Coerência Óptica , Adulto Jovem
7.
Graefes Arch Clin Exp Ophthalmol ; 257(7): 1467-1472, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31111251

RESUMO

BACKGROUND: It has been shown in the literature that the Valsalva manoeuvre influences ocular perfusion by changing intraocular pressure and central retinal venous pressure (CRVP). High-resistance wind instrument (HRWI) playing is a common situation resembling a Valsalva manoeuvre. The aim of this investigation was to explore the influence of amateur trumpet playing on CRVP. METHODS: The left eyes of 20 healthy non-professional trumpet players (median age 26, range 19-52 years; 17 males, 3 females) were included in this investigation. Subjects, sitting at a slit lamp, were asked to play the tone b' flat with their own mouthpiece on the same trumpet for at least 30 s with moderate loudness. The following data were obtained: intraocular pressure (IOP) by applanation tonometry before and during playing, CRVP by contact lens dynamometry before and during playing, airway pressure (AirP) using a pressure sensor during playing and blood pressure and heart rate using the common cuff method before and during playing. RESULTS: The results are presented as the medians before vs during playing: a calculated mean ophthalmic artery pressure of 66 vs 72 mmHg, heart rate of 76 vs 82 beats per minute, airway pressure of 0 vs 17 mmHg, IOP 12 vs 13 mmHg and CRVP of 24 vs 55 mmHg (Wilcoxon test: p = 0.00009), respectively. A correlation between the CRVP during playing and the height of the spontaneous CRVP is noted (Spearman rank correlation coefficient: ρ = 0.68). CONCLUSIONS: Amateur trumpet playing increases CRVP, airway pressure and IOP. The increase in CRVP is greater than that of the intraocular pressure. The increase in CRVP seems to be more important for retinal perfusion changes during trumpet playing than the increase of IOP. It can be hypothesised that high airway pressure during playing may cause a permanent increase in CRVP, at least in a subgroup of trumpet players.


Assuntos
Pressão Venosa Central/fisiologia , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Retina/fisiopatologia , Manobra de Valsalva/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Tonometria Ocular , Adulto Jovem
8.
Invest Ophthalmol Vis Sci ; 60(5): 1566-1570, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30995313

RESUMO

Purpose: To test the hypothesis that oxidative stress in the outer retina (OR = distance from external limiting membrane to the retinal pigment epithelium-choroid boundary) can be detected by using antioxidants (AOs) to correct an impaired light-evoked response as measured by optical coherence tomography (OCT). Methods: C57BL/6J mice were maintained in the dark for ∼20 hours and studied by OCT before and after 1 hour of light exposure. OR thickness in dark or light was measured, and the light-dark difference (i.e., the photoresponse) was calculated. Subgroups of mice were given either saline or d-cis-diltiazem (an inducer of transient and nondamaging OR oxidative stress) ± methylene blue (24 hours before examination) and α-lipoic acid (1 hour before examination); one group was kept only in the dark and given only AOs. Results: In uninjected or saline-injected control mice, the OR showed a similar and reproducible light-induced expansion; dark-adapted mice given AOs did not increase dark-adapted OR thickness. The d-cis-diltiazem-treated mice had no photoresponse (P > 0.05). The d-cis-diltiazem-treated mice given AOs corrected (P < 0.05) the suppressed OR photoresponse, indicating the presence of oxidative stress. Conclusions: QUEnch-assiSTed (QUEST) OCT reproduced results from previous gold standard assays, showing that oxidative stress impairs the OR photoresponse and that d-cis-diltiazem produces OR oxidative stress. We envision future applications of QUEST OCT in a range of oxidative stress-based retinopathies.


Assuntos
Lâmina Basilar da Corioide/patologia , Estresse Oxidativo , Lesões Experimentais por Radiação/diagnóstico por imagem , Retina/efeitos da radiação , Degeneração Retiniana/diagnóstico por imagem , Epitélio Pigmentado da Retina/patologia , Animais , Antioxidantes , Bloqueadores dos Canais de Cálcio/farmacologia , Adaptação à Escuridão , Diltiazem/farmacologia , Luz/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/fisiologia , Estimulação Luminosa , Lesões Experimentais por Radiação/fisiopatologia , Retina/efeitos dos fármacos , Retina/fisiopatologia , Degeneração Retiniana/fisiopatologia , Tomografia de Coerência Óptica
9.
Mol Autism ; 10: 19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011411

RESUMO

Background: Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Disturbances in glutamatergic and GABAergic signaling that lead to synaptic changes and alter the balance between excitation and inhibition in the developing brain are consistently found in ASD. One of the hallmarks of these disorders is hypersensitivity to sensory stimuli; however, little is known about its underlying causes. Since the retina is the part of the CNS that converts light into a neuronal signal, we set out to study how it is affected in adolescent mice prenatally exposed to valproic acid (VPA), a useful tool to study ASD endophenotypes. Methods: Pregnant female mice received VPA (600 mg/kg, ip) or saline at gestational day 11. Their male adolescent pups (P29-35) were behaviorally tested for anxiety and social interaction. Proteins known to be related with ASD were quantified and visualized in their retinas by immunoassays, and retinal function was assessed by full-field scotopic electroretinograms (ERGs). Results: Early adolescent mice prenatally exposed to VPA displayed impaired social interest and increased anxiety-like behaviors consistent with an ASD phenotype. The expression of GABA, GAD, synapsin-1, and FMRP proteins were reduced in their retinas, while mGluR5 was increased. The a-wave amplitudes of VPA-exposed were smaller than those of CTR animals, whereas the b-wave and oscillatory potentials were normal. Conclusions: This study establishes that adolescent male mice of the VPA-induced ASD model have alterations in retinal function and protein expression compatible with those found in several brain areas of other autism models. These results support the view that synaptic disturbances with excitatory/inhibitory imbalance early in life are associated with ASD and point to the retina as a window to understand their subjacent mechanisms.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Retina/metabolismo , Potenciais de Ação , Animais , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/metabolismo , Endofenótipos , Feminino , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Receptores de GABA/genética , Receptores de GABA/metabolismo , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismo , Retina/fisiopatologia , Comportamento Social , Sinapsinas/genética , Sinapsinas/metabolismo , Ácido Valproico/toxicidade
10.
Doc Ophthalmol ; 139(2): 99-111, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31016437

RESUMO

PURPOSE: To evaluate three measures of inner retina function, the pattern electroretinogram (pERG), the photopic negative response (PhNR), and the post-illumination pupil response (PIPR) in diabetics with and without nonproliferative diabetic retinopathy (NPDR). METHODS: Fifteen non-diabetic control subjects and 45 type 2 diabetic subjects participated (15 have no clinically apparent retinopathy [NDR], 15 have mild NPDR, and 15 have moderate/severe NPDR). The pERG was elicited by a contrast-reversing checkerboard pattern, and the PhNR was measured in response to a full-field, long-wavelength flash presented against a short-wavelength adapting field. The PIPR was elicited by a full-field, 450 cd/m2, short-wavelength flash. All responses were recorded and analyzed using conventional techniques. One-way ANOVAs were performed to compare the pERG, PhNR, and PIPR among the control and diabetic groups. RESULTS: ANOVA indicated statistically significant differences among the control and diabetic subjects for all three measures. Holm-Sidak post hoc comparisons indicated small, nonsignificant reductions in the pERG (8%), PhNR (8%), and PIPR (10%) for the NDR group compared to the controls (all p > 0.25). In contrast, there were significant reductions in the pERG (35), PhNR (34%), and PIPR (30%) for the mild NPDR group compared to the controls (all p < 0.01). Likewise, there were significant reductions in the pERG (40%), PhNR (32%), and PIPR (32%) for the moderate/severe NPDR group compared to the controls (all p < 0.01). CONCLUSION: Abnormalities of the pERG, PhNR, and PIPR suggest inner retina neural dysfunction in diabetics who have clinically apparent vascular abnormalities. Taken together, these measures provide a noninvasive, objective approach to study neural dysfunction in these individuals.


Assuntos
Retinopatia Diabética/fisiopatologia , Retina/fisiopatologia , Células Ganglionares da Retina/fisiologia , Adulto , Análise de Variância , Visão de Cores/fisiologia , Eletrorretinografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Pupila/efeitos da radiação
11.
Nutrients ; 11(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987058

RESUMO

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Suplementos Nutricionais , Retina/efeitos dos fármacos , Neovascularização Retiniana/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Degeneração Neural , Estresse Oxidativo/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Retina/fisiopatologia , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Retiniana/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
12.
Doc Ophthalmol ; 139(1): 45-57, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30945053

RESUMO

PURPOSE: The aim of this study was to examine the ophthalmological characteristics and genotypes of patients with congenital retinal pathologies, who display a bull's-eye maculopathy in the fundus, along with a negative scotopic electroretinogram. METHODS: We analysed the results of five patients showing both a bull's-eye maculopathy, as well as a negative scotopic ERG evoked by a bright flash. Their median age was 39 years (range 11-63 years): three males and two females. All underwent a comprehensive examination with determination of distant visual acuity (ETDRS) and recording of the full-field ERG (scotopic and photopic). Fundus, OCT, and FAF images were obtained, the kinetic visual field was determined, and colour vision (D-15) was tested in most patients. Targeted gene panel sequencing was performed on peripheral blood. RESULTS: One patient carried a homozygous ABCA4 mutation and an additional heterozygous variant in CRX. Two of the five patients were shown to have a heterozygous mutation in the CRX gene, one of whom had an additional heterozygous ABCA4 mutation. Two patients had the common heterozygous mutation c.2413G>A;p.Arg838His in GUCY2D. In all of the patients, there was a reduction in the amplitude of the b-wave with a regular a-wave amplitude in the scotopic bright-flash ERG. CONCLUSIONS: The five patients with bull's-eye maculopathy along with a negative ERG had differing genotypes. Mutations were found in the CRX gene (2 patients), the ABCA4 gene (1 patient), and the GUCY2D gene (2 patients).


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Guanilato Ciclase/genética , Proteínas de Homeodomínio/genética , Degeneração Macular/genética , Degeneração Macular/fisiopatologia , Mutação , Receptores de Superfície Celular/genética , Retina/fisiopatologia , Transativadores/genética , Adulto , Criança , Análise Mutacional de DNA , Eletrorretinografia , Feminino , Angiofluoresceinografia , Humanos , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Visão Noturna/fisiologia , Estimulação Luminosa , Acuidade Visual/fisiologia , Adulto Jovem
13.
Doc Ophthalmol ; 139(1): 59-65, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30972611

RESUMO

PURPOSE: The purpose of this study was to compare electroretinographic (ERG) responses of preterm schoolchildren, with and without a history of retinopathy of prematurity (ROP) with those of full-term schoolchildren by using a portable ERG device (RETeval system). METHODS: Twenty five prematurely born schoolchildren with a mean gestational age of 27 + 1/7w (range 23-30w) and a mean birth weight of 1030 g (range 580-1700 g) who were 6.9 ± 2.2 years old participated in the study (premature group). A further subdivision according to a history of ROP (ROP+ group) or its absence (ROP- group) was introduced. Twenty eight healthy full-term schoolchildren with an average age of 8.6 ± 1.9 years participated as the control group. 30-Hz flicker ERG responses were obtained, and implicit times and amplitudes were compared between the groups. RESULTS: 30-Hz flicker ERG implicit times showed a significant difference between all three groups of children. The mean value of the implicit time in the term group was 25.76 ± 0.9 ms, whereas in the preterm ROP + group it was 28.96 ± 1.0 ms and in the preterm ROP- group it was 26.87 ± 1.5 ms. 30-Hz flicker ERG amplitudes did not show significant difference between term children and children born prematurely with or without ROP. CONCLUSIONS: Prematurely born schoolchildren exhibit longer implicit time of the 30-Hz flicker ERG response compared to controls, suggesting a possible abnormality of the retinal cone system function. Under such circumstances, portable ERG device might be used clinically as a screening tool for retinal function evaluation in prematurely born children.


Assuntos
Eletrorretinografia/instrumentação , Células Fotorreceptoras Retinianas Cones/fisiologia , Retinopatia da Prematuridade/fisiopatologia , Peso ao Nascer , Criança , Feminino , Idade Gestacional , Humanos , Recém-Nascido Prematuro , Masculino , Estimulação Luminosa , Retina/fisiopatologia
14.
Doc Ophthalmol ; 138(3): 205-215, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30929108

RESUMO

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum protocol for clinical testing but encourages additional ERG testing when appropriate. This ISCEV extended protocol describes methods to record and evaluate a light-adapted (LA) ERG stimulus-response series with increasing flash strengths. The LA ERG stimulus-response series (also referred to as the luminance-response or intensity-response series in the published literature) can characterise generalised cone system function more comprehensively than the ISCEV standard LA ERGs alone. The amplitude of LA ERG a-waves, arising from cones and cone off-bipolar cells, typically shows a saturating function. The LA ERG b-wave amplitudes, which arise primarily from activity of retinal bipolar cells, show an amplitude peak followed by a nonzero plateau (the "photopic hill" phenomenon). This ISCEV extended protocol specifies a stimulus-response series suitable to evaluate generalised dysfunction affecting the LA retina, to aid in distinguishing between the on- and off-responses of the cone system and to monitor ERG changes in these characteristics. The LA ERG stimulus-response series for a- and b-waves is recorded to a sequence of nine flash stimuli ranging from 0.03 to 300 cd s m-2, superimposed on a standard background of 30 cd m-2. A shorter protocol is also presented to measure the mid-range of the function (the "photopic hill") using 5 flash stimuli.


Assuntos
Protocolos Clínicos/normas , Eletrorretinografia/métodos , Oftalmopatias Hereditárias/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Luz , Miopia/fisiopatologia , Cegueira Noturna/fisiopatologia , Estimulação Luminosa/métodos , Retina/fisiopatologia , Adulto , Humanos , Oftalmologia/organização & administração , Células Fotorreceptoras Retinianas Cones/fisiologia , Sociedades Médicas/organização & administração
15.
Doc Ophthalmol ; 139(1): 21-32, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30927186

RESUMO

BACKGROUND: Albinism patients have poor visual acuity in addition to hypopigmentation. Their foveal anatomy is abnormal, but correlation with function is incompletely understood. This study correlates retinal electrophysiology, visual acuity and optical coherence tomography (OCT) anatomy in albinism patients and compares with age-similar controls. METHODS: Institutional Review Board approval was obtained (IRB# 201408782). Patients were recruited from clinical practice. Inclusion criteria were at least three clinical features of albinism including iris transillumination, nystagmus, fundus hypopigmentation, or foveal hypoplasia on OCT and/or molecular genetic confirmation. Diagnosys (Lowell, Mass) full-field ERG (ffERG) and VERIS multifocal ERG (mfERG; Electro-Diagnostic Imaging, Milpitas, California) were obtained using standard International Society for Clinical Electrophysiology of Vision protocols. The mfERG protocol was a 4-min 103-hexagon protocol covering approximately 40° in diameter of central retina. Control subjects without albinism were recruited by in-hospital notices and invitations in clinic. OCT central thickness was recorded, and an OCT foveal score was calculated. Nonparametric permutation testing was utilized to determine the statistical significance. RESULTS: A total of 16 albinism patients and 19 age-similar controls were recruited. Four of 16 albinism patients had no nystagmus. Seventeen non-albinism controls had no ocular disorder other than refractive error. Two controls had infantile nystagmus with normal maculas on OCT. There was no statistically significant difference in mfERG amplitude or latency between albinism patients with or without nystagmus (lowest p = 0.68; 0.54, respectively). mfERG: 12 of 16 (75%) albinism patients had average ring 1 amplitudes within one standard deviation of controls despite having abnormal foveal anatomy on OCT. Patients averaged shorter latencies in rings 1 and 2 than controls (p = 0.005, p = 0.02). Patients averaged higher amplitudes than controls in rings 4, 5 and 6 (p = 0.03, p = 0.006, p = 0.004). There was no significant correlation between visual acuity and mfERG amplitudes in any ring (smallest p = 0.15). ffERG: Patients averaged higher amplitudes on 30 Hz flicker (p = 0.008). In all conditions, albinism patients had higher amplitude a-waves (p ≤ 0.03). B-waves were higher amplitude than controls in light-adapted 3.0 (p = 0.03). There was no statistical correlation between ffERG amplitudes and visual acuity (smallest p = 0.45). OCT: In albinism patients, thicker central macula on OCT correlated with lower mfERG amplitudes in all rings except for ring 1 (p < 0.05) and lower ffERG a-wave amplitudes on dark-adapted 0.01 (p = 0.003). Macular thickness on OCT did not correlate with visual acuity (p = 0.51); OCT foveal score did (p = 0.0004). CONCLUSIONS: Amplitude of mfERG does not correlate with visual acuity in any ring in patients with albinism. The slope of the change in amplitude from central to peripheral rings on the mferg is significantly different in albinism patients versus controls whether or not nystagmus is present. The decreased slope of change in amplitudes from center to periphery of the macula in albinism patients indicates changes in macular topography that are more important to visual deficits than the foveal depression.


Assuntos
Albinismo Oculocutâneo/fisiopatologia , Fóvea Central/patologia , Retina/fisiopatologia , Acuidade Visual/fisiologia , Adolescente , Adulto , Criança , Eletrorretinografia/métodos , Feminino , Fóvea Central/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Nistagmo Patológico/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Adulto Jovem
16.
Invest Ophthalmol Vis Sci ; 60(4): 1122-1131, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901388

RESUMO

Purpose: Dark-adapted visual fields were obtained from patients with inherited retinal degeneration (IRD) and controls to evaluate the effect that age, retinal region, and disease had on scotopic sensitivity. Intra- and intersession test-retest repeatabilities for patients and controls were measured to establish significant change for longitudinal studies. Methods: A total of 41 patients with IRD and 30 controls had one eye dilated and dark-adapted for 40 minutes. Scotopic sensitivity was measured with a Medmont dark-adapted chromatic (DAC) perimeter (size V stimulus, 200-ms duration, background luminance < 0.0001 cd/m2, dynamic range 0-75 decibel [dB]). Mixed effects analysis was performed to analyze age, retinal eccentricity, and sensitivity. The intra-/intersession coefficients of repeatability (CR) were calculated for controls and patients with IRD. Results: Each additional year was associated with lower sensitivity (-0.22 dB) per year in normal controls over age 50 compared to younger controls (12-49 years). The superior field had lower sensitivity than the inferior, but the nasal field was not different compared to the temporal field in normal controls. The CR for intra- and intersession testing on mean sensitivity (MS)/pointwise sensitivity (PWS) were ±1.5/±8.5 and ±3.3/±9.8 dB, respectively, for patients with IRD. Control MS/PWS CR were ±1.5/±6.1 dB for intrasession and ±1.7/±6.8 dB for intersession DAC perimetry. Conclusions: The DAC perimeter is an important asset because it tests a wide field of scotopic vision. The CR are comparable to those of other perimetry devices. Effects of age and retinal region should be considered when assessing scotopic sensitivity measured with the DAC perimeter.


Assuntos
Visão Noturna/fisiologia , Retina/fisiopatologia , Degeneração Retiniana/fisiopatologia , Escotoma/fisiopatologia , Campos Visuais/fisiologia , Adolescente , Adulto , Idoso , Criança , Adaptação à Escuridão/fisiologia , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Degeneração Retiniana/genética , Escotoma/genética , Acuidade Visual , Testes de Campo Visual/métodos , Adulto Jovem
17.
Invest Ophthalmol Vis Sci ; 60(4): 1132-1143, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901771

RESUMO

Purpose: Bardet-Biedl syndrome (BBS) is an archetypical ciliopathy caused by defective ciliary trafficking and consequent function. Insights gained from BBS mouse models are applicable to other syndromic and nonsyndromic retinal diseases. This progressive characterization of the visual phenotype in three BBS mouse models sets a baseline for testing therapeutic interventions. Methods: Longitudinal acquisition of electroretinograms, optical coherence tomography scans, and visual acuity using the optomotor reflex in Bbs6/Mkks, Bbs8/Ttc8, and Bbs5 knockout mice. Gene and protein expression analysis in vivo and in vitro. Results: Complete loss of BBS5, BBS6, or BBS8 leads to different rates of retinal degeneration and visual function over time. BBS8-deficient mice showed the fastest rate of degeneration, and BBS8 seems to be required for cone photoreceptors to reach functional maturity. In contrast, the loss of BBS5 (a further BBSome component) showed very little degeneration. Loss of BBS8 versus BBS5 resulted in different physiologic responses both in vivo and in vitro. BBS6-deficient mice show a slower rate of degeneration with both rod and cone function reducing at a similar rate. Conclusions: The mouse models analyzed show distinct and diverging courses of degeneration upon loss of BBS5, BBS6, or BBS8, which can be used as a benchmark to test therapeutic interventions. Close consideration of the different phenotypes reveal subtle but important differences relating to their function. Because we also see differences in terms of phenotype depending on the type of visual assessment used, our data highlight the importance of using a combinatorial approach for assessment of visual function.


Assuntos
Síndrome de Bardet-Biedl/fisiopatologia , Modelos Animais de Doenças , Retina/fisiopatologia , Degeneração Retiniana/fisiopatologia , Visão Ocular/fisiologia , Envelhecimento/fisiologia , Animais , Síndrome de Bardet-Biedl/genética , Western Blotting , Proteínas de Transporte/genética , Eletrorretinografia , Técnicas de Genotipagem , Chaperoninas do Grupo II/genética , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Camundongos Mutantes , Proteínas Associadas aos Microtúbulos/genética , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Degeneração Retiniana/genética , Transdução de Sinais/fisiologia , Tomografia de Coerência Óptica
18.
Invest Ophthalmol Vis Sci ; 60(4): 1165-1174, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30908580

RESUMO

Purpose: To determine if there is structural and functional recovery of the retina from light induced retinal degeneration, and to evaluate the role of the oxidative stress response elements Nrf2, SOD1, DJ-1, and Parkin in such a recovery process. Methods: Eyes from C57BL/6J (B6J) mice and from oxidative stress response-deficient strains of mice were treated with intense light using the fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) model. Fundus photographs, optical coherence tomography (OCT) images, and electroretinography (ERG) responses were obtained before the injury, during the "maximal injury phase" (days 4-7) and during the "recovery phase" (days 14-16) post light exposure and were evaluated for retinal damage and assessed for evidence of recovery from the injury. Results: We demonstrate that mice treated with a sub-lethal FCD-LIRD protocol show an initial acute retina injury phase peaking between days 4 to 7 followed by a recovery phase in which the outer retinal thickness/volume and retinal function partially recover. These observations are reproduced in B6J mice and in mice lacking oxidative stress response enzymes (SOD1, DJ-1, and Parkin) or the oxidative stress response master regulator Nrf2. Conclusions: Our data indicate that retinal recovery from injury can proceed via pathways that are independent from the common oxidative stress response elements Nrf2, SOD1, DJ-1, and Parkin. Furthermore, the model of retinal recovery from injury that we describe here mimics changes seen in a variety of clinical entities and may provide an excellent platform for dissecting general pathways of retinal recovery from sub-lethal injury.


Assuntos
Modelos Animais de Doenças , Fator 2 Relacionado a NF-E2/metabolismo , Lesões Experimentais por Radiação/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Degeneração Retiniana/fisiopatologia , Superóxido Dismutase-1/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Eletrorretinografia , Feminino , Luz/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/deficiência , Estresse Oxidativo , Fotografação , Lesões Experimentais por Radiação/metabolismo , Retina/diagnóstico por imagem , Retina/fisiopatologia , Retina/efeitos da radiação , Degeneração Retiniana/metabolismo , Tomografia de Coerência Óptica
19.
Doc Ophthalmol ; 138(3): 241-246, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30820731

RESUMO

PURPOSE: Cockayne syndrome is a rare autosomal recessive disease, also known as a progeria disorder, causing dwarfism, senile appearance and multiple systemic affections. Ophthalmic abnormalities are frequent, for example, in the forms of pigmentary retinopathy with low visual acuity. We present two genetic-confirmed cases with a detailed electrophysiological exploration of their retinal findings. METHODS: Complete ophthalmic exploration is undertaken, including full-field electroretinogram under ISCEV guidelines and multifocal electroretinogram (RETI-scan science, Roland-Consult, Germany), ultra-wide-field retinography and autofluorescence (Optomap, Optos PLC, Dunfermline, Scotland, UK) and macular and retinal nerve fibre layer optical coherence tomography (Cirrus, Carl-Zeiss Meditec, Inc, Dublin, CA). RESULTS: Both cases presented with CSA/ERCC8 mutation and low visual acuity. Diffuse pigmentary retinopathy with macular atrophy was found in ultra-wide-field retinography and autofluorescence. Electrophysiological testing reported wide retinal dysfunction on both cone and rod system with macular involvement. CONCLUSIONS: Pigmentary retinopathy in CS could translate a wide dysfunction of the retina with major affection of external retinal layers of both cone and rod cells. Macular implication is also present and could explain progressive vision loss in such cases.


Assuntos
Síndrome de Cockayne/fisiopatologia , Retina/fisiopatologia , Retinite Pigmentosa/fisiopatologia , Adulto , Síndrome de Cockayne/genética , Enzimas Reparadoras do DNA/genética , Técnicas de Diagnóstico Oftalmológico , Eletrorretinografia/métodos , Feminino , Humanos , Masculino , Mutação , Tomografia de Coerência Óptica/métodos , Fatores de Transcrição/genética , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia
20.
Invest Ophthalmol Vis Sci ; 60(4): 944-953, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30849170

RESUMO

Purpose: Evidence from animals and blind humans suggests that early visual experience influences the developmental calibration of auditory localization. Hypothesizing that unilateral amblyopia may involve cross-modal deficits in spatial hearing, we measured the precision and accuracy of sound localization in humans with amblyopia. Methods: All participants passed a standard hearing test. Experiment 1 measured sound localization precision for click stimuli in 10 adults with amblyopia and 10 controls using a minimum audible angle (MAA) task. Experiment 2 measured sound localization error (i.e., accuracy) for click train stimuli in 14 adults with amblyopia and 16 controls using an absolute sound localization task. Results: In Experiment 1, the MAA (mean ± SEM) was significantly greater in the amblyopia group compared with controls (2.75 ± 0.30° vs. 1.69 ± 0.09°, P = 0.006). In Experiment 2, the overall sound localization error was significantly greater in the amblyopia group compared with controls (P = 0.047). The amblyopia group also showed significantly greater sound localization error in the auditory hemispace ipsilateral to the amblyopic eye (P = 0.036). At a location within this auditory hemispace, the magnitude of sound localization error correlated significantly with deficits in stereo acuity (P = 0.036). Conclusions: The precision and accuracy of sound localization are impaired in unilateral amblyopia. The asymmetric pattern of sound localization error suggests that amblyopic vision may interfere with the development of spatial hearing via the retinocollicular pathway.


Assuntos
Ambliopia/fisiopatologia , Perda Auditiva/fisiopatologia , Retina/fisiopatologia , Localização de Som/fisiologia , Colículos Superiores/fisiopatologia , Estimulação Acústica , Adulto , Mapeamento Encefálico , Calibragem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pessoas com Deficiência Auditiva , Psicometria , Adulto Jovem
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