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PURPOSE: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus (VZV) induced acute retinal necrosis (ARN), and to explore the effect of viral genotypes on clinical manifestations. METHODS: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase (Tinflection) was estimated. Variations in viral genomes were detected by metagenomic sequencing. RESULTS: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9×107 (1.1×107-1.1×108) copies/mL. The average duration of retinitis was 5±3 weeks. The average Tinflection was 4.2±1.6 days. Tinflection was correlated with the duration of retinitis (P=0.025). Patients with VZVs carrying the p.S715* variation in ribonucleotide reductase (RNR) subunit 1 gene had lower initial viral loads (median 1.3×107 copies/ml) than those without (median 1.1×108 copies/ml; adjusted P=0.030). CONCLUSIONS: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in ARN patients. Loss-of-function variation in RNR gene might be correlated with lower virulence of VZV.
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OBJECTIVE: To describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DESIGN: A retrospective observational case series. PARTICIPANTS: We examined 6 eyes in 3 patients (1 with multiple myeloma, 1 with membranous nephropathy, and 1 with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)âBruch's membrane complex and acquired serous retinal detachment. METHODS: Fundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain OCT, swept-source OCT (SS-OCT), en face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. MAIN OUTCOME MEASURES: Multimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. RESULTS: Bilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPEâBruch's membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and "angiographically silent" serous retinal detachment in patients with systemic immunoglobulin light chain deposition. CONCLUSIONS: We have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
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PURPOSE: To evaluate changes in retinal and choroidal vascularity using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE). METHODS: In this prospective, cross-sectional study, 48 SLE patients and 40 healthy control (group HC) participants were included. The SLE patients were divided into two subgroups: patients with SLE with no ocular disease (group I) and patients with SLE with signs of retinopathy (group II). The superficial vessel density (SVD), deep vessel density (DVD), peripapillary retinal vessel densities (pRVD), choroidal thickness (ChT), and choroidal vascularity including total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) were measured using SS-OCT/OCTA. Physical and ophthalmic examinations as well as the assessments of immunological markers were performed. The results of SS-OCT/OCTA were compared between group I, group II, and group HC, while the correlations among the parameters were analyzed. RESULTS: The SVD, DVD, and pRVD were found to be significantly lower in SLE patients than group HC, especially in SLE patients with signs of retinopathy. ChT were found to be significantly higher in group II. CVI was positively correlated with SVD and DVD in the fovea, as well as the foveal and parafoveal thickness. A significant decrease in SVD and DVD in the fovea among subjects positive for anti-dsDNA antibodies was noted. CONCLUSIONS: The application of OCTA in the evaluation of microvasculature may be useful in subclinical changes. Retinal microvascular density decreased in patients with SLE with greater severity of SLE. Disturbed retinal circulation was related to SLE disease activity, disease duration, CVI, and being positive for anti-dsDNA antibodies. The study results also suggest that SLE with signs of retinopathy may affect the choroid with increases in LA, SA, TCA, and ChT.
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Lúpus Eritematoso Sistêmico , Doenças Retinianas , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Estudos Transversais , Retina , Corioide/irrigação sanguínea , Vasos Retinianos , Angiofluoresceinografia/métodos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.
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DNA Mitocondrial , Lipopolissacarídeos , Animais , DNA Mitocondrial/genética , Injeções Intravítreas , Proteínas de Membrana/metabolismo , Mitocôndrias , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , RatosRESUMO
OBJECTIVE: To analyze the blood flow in retrobulbar vessels in systemic lupus erythematosus (SLE) by color Doppler imaging (CDI) and to investigate the associations between immunological markers, retinal abnormalities, disease activity, and vascular parameters. METHODS: We examined 30 patients with SLE who were aged 32.1 ± 11.6 years with a disease duration of 68.0 ± 55.6 months and 30 participants in a control group. The peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI) of the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs) were determined. Physical and ophthalmic examinations with assessments of immunological markers were performed. All parameters were compared between SLE patients and normal controls while the correlations among parameters were analyzed. RESULTS: In the SLE group, CDI confirmed blood flow abnormalities in the CRA and PCAs, with significantly lower blood flow velocities and increased RI and PI (p < 0.05). There was a significantly negative correlation between disease duration and EDV in the CRA, PCA, and OA (p = 0.0423, 0.0453, 0.0448). There was also a significant relationship between the SLE Disease Activity Index and the PI of the OA (p = 0.0367). The patients who had received biological agents (Rituximab) had lower EDV in the CRA and PCA (p = 0.0026, 0.028). SLE patients with kidney or CNS involvement had a significant increase in the PI in the OA (p = 0.0287). The PSV and EDV in the CRA were significantly related to creatinine (p = 0.0007 and 0.0418). We also noted a significant decreased EDV in the CRA and an increased RI in the OA among participants positive for anti-dsDNA antibodies (p = 0.0331 and 0.0228). CONCLUSIONS: Retrobulbar circulatory disturbances were detected in SLE patients by CDI. These findings seem likely to affect smaller vessels like the CRA and PCA. However, the presence of measurable changes in the OA is generally indicative of a coexistent nephropathy or central nervous system (CNS) vasculitis. Creatinine, the disease activity index, being positive for anti-dsDNA, and receiving biological agents were associated with measurable changes on the retrobulbar blood flow.
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Artérias Ciliares , Lúpus Eritematoso Sistêmico , Adulto , Anticorpos Antinucleares , Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Ciliares/diagnóstico por imagem , Artérias Ciliares/fisiologia , Humanos , Artéria Oftálmica/diagnóstico por imagem , Artéria Oftálmica/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Adulto JovemRESUMO
BACKGROUND: To investigate the relationship between an oval optic disc and the occurrence of myopic foveoschisis (MF) using swept-source optic coherence tomography (SS-OCT). METHODS: Fifty eyes of 25 patients with unilateral MF were included in this retrospective observational study. The biometric features of the optic disc and peripapillary structures were evaluated using SS-OCT. RESULTS: The ovality index (OI) of the optic disc was significantly smaller (P = 0.003) and the optic disc tilt angle was greater (P = 0.023) in the eyes with MF than in the contralateral eyes. The optic disc tilt angle was significantly correlated with the OI (P = 0.000). Generalized estimating equation (GEE) model (linear regression) demonstrated that spherical equivalent refraction (P = 0.001), narrow macular staphyloma (P = 0.001) and the occurrence of MF (P = 0.026) were the independent factors associated with the OI. Narrow macular staphyloma was more frequent (P = 0.020) and the staphyloma was deeper (P = 0.006) in eyes with MF. GEE model (logistic regression) revealed that narrow macular staphyloma was the only independent factor related to the occurrence of MF (P = 0.013). CONCLUSIONS: An oval optic disc in eyes with MF resulted from the increased tilt around the vertical disc axis. The optic disc tilt was related to narrow macular staphyloma, which was the only independent factor associated with the occurrence of MF. The clinical relevance needs further exploration through longitudinal analysis.
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Miopia , Disco Óptico , Biometria , Humanos , Miopia/complicações , Refração Ocular , Tomografia de Coerência Óptica/métodosRESUMO
OBJECTIVE: To investigate the prognostic value of derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) in patients with advanced HER2 positive breast cancer treated with trastuzumab emtansine. METHODS: Fifty one patients with advanced HER2 positive breast cancer who received T-DM1 treatment in Harbin Medical University Cancer Hospital were selected. The clinical data and blood test indexes were collected, and the ROC curve determined the optimal cut-off value. Kaplan-Meier survival curve and Cox regression model was used to analyze the effect of different levels of dNLR,LDH,LNI (dNLR combined with LDH index) before and after T-DM1 treatment on the survival of patients. RESULTS: The median PFS and OS of the patients with advanced HER2 positive breast cancer who received T-DM1 treatment were 6.9 months and 22.2 months, respectively. The optimal cut-off value of LDH and dNLR before T-DM1 treatment was 244 U / L (P = 0.003) and 1.985 (P = 0.013), respectively. Higher LDH and dNLR were significantly correlated with shorter median PFS and OS (P < 0.05). The median PFS of patients with LNI (0), LNI (1) and LNI (2) were 8.1 months, 5.5 months and 2.3 months, respectively, P = 0.007. Univariate and multivariate analysis showed that LDH > 244 U / L, dNLR > 1.985, LNI > 0, ECOG ≥1 and HER-2 (IHC2 +, FISH+) before the T-DM1 treatment were the poor prognostic factors. LDH uptrend after the T-DM1 treatment also predicted poor prognosis. CONCLUSION: Serum LDH > 244 U / L and dNLR > 1.985 before the T-DM1 treatment were prognostic risk factors for patients with advanced HER2 positive breast cancer receiving T-DM1 treatment. The higher LNI score was significantly associated with shorter PFS and OS. LDH uptrend after T-DM1 treatment was also related to the poor prognosis.
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Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos/estatística & dados numéricos , Biomarcadores Tumorais/sangue , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfócitos , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/metabolismo , Valores de Referência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To observe the changes of viral load in aqueous humour samples and visual outcomes in varicella zoster virus (VZV)-induced acute retinal necrosis (ARN). METHODS: Observational retrospective study. Medical records and viral load measured by real-time quantitative polymerase chain reaction (qPCR) of 20 eyes with VZV-induced ARN were reviewed. RESULTS: The mean viral load at presentation was 5.7 × 107 ± 9.7 × 107 copies/mL. An initial plateau phase for viral load lasting up to 2 weeks occurred in most eyes (18 eyes, 90%). In the following logarithmic reduction phase, the mean slope of the decline in viral load was -0.103 ± 0.029 log/day, and the expected time for half reduction of the initial viral load was 3.2 ± 1.0 days. At the end of the first 8-week's antiviral treatment, the viral load was below detection threshold in all 20 eyes (100.0%). The mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 1.1 ± 0.7 (Snellen equivalent 20/250) to 0.7 ± 0.6 (Snellen equivalent 20/100) after a follow-up of 8.6 ± 2.0 months. Thirteen of the 20 eyes (65.0%) suffered retinal detachment and underwent vitrectomy. The initial viral load was the independent predictive factor of logMAR BCVA at the last follow-up (ß = 0.745, P < 0.001). CONCLUSIONS: The observation of viral load changes by qPCR was useful for better monitoring of therapeutic efficacy and deciding needed antiviral duration in VZV-induced ARN patients.
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Infecções Oculares Virais , Herpes Zoster Oftálmico , Síndrome de Necrose Retiniana Aguda , Antivirais/uso terapêutico , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/tratamento farmacológico , Herpesvirus Humano 3/genética , Humanos , Síndrome de Necrose Retiniana Aguda/diagnóstico , Síndrome de Necrose Retiniana Aguda/tratamento farmacológico , Estudos Retrospectivos , Carga ViralRESUMO
BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light-or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING path-way and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.
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Animais , Ratos , DNA Mitocondrial/genética , Lipopolissacarídeos , Injeções Intravítreas , Proteínas de Membrana/metabolismo , Mitocôndrias , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismoRESUMO
PURPOSE: To investigate the macular vessel density and thickness in macular-on rhegmatogenous retinal detachment (RRD) after vitrectomy with gas and silicone oil (SO) tamponade. METHODS: Patients with macular-on RRD eyes, treated with a single successful vitrectomy with gas or SO tamponade and a minimum 30 months follow-up, were reviewed. Best-corrected visual acuity (BCVA), macular vessel density and retinal thickness by using optical coherence tomography angiography, were compared to the contralateral eyes. RESULTS: Sixteen eyes with gas tamponade and 17 eyes with SO tamponade were included in the study. LogMAR best-corrected visual acuity (BCVA) slightly improved from 0.25 ± 0.18 (Snellen 20/36) to 0.17 ± 0.23 (Snellen 20/30) in eyes with gas tamponade, and decreased from 0.30 ± 0.22 (Snellen 20/40) to 0.49 ± 0.28 (Snellen 20/62) in eyes with SO tamponade. The parafoveal vessel densities in superficial vascular complex (SVC) and the corresponding inner retinal thickness (IRT) were similar between the affected eyes and the contralateral eyes in gas tamponade group (P = 0.578, P = 0.943), while significantly reduced in the affected eyes, compared to the contralateral eyes in SO tamponade group (P < 0.001, P < 0.001). CONCLUSION: Eyes in SO tamponade group had worse BCVA, lower SVC vessel densities and thinner corresponding IRT after vitrectomy for macular-on RRD, than those in gas tamponade group.
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Macula Lutea , Descolamento Retiniano , Tamponamento Interno , Humanos , Descolamento Retiniano/cirurgia , Óleos de Silicone , VitrectomiaRESUMO
PURPOSE: To compare the anatomical and functional outcomes of macular hole (MH)-associated retinal detachment after vitrectomy with the internal limiting membrane (ILM) insertion technique or the inverted ILM flap technique. METHODS: In this retrospective observational study, we reviewed the medical records of 49 eyes with MH-associated retinal detachment that underwent vitrectomy with the ILM insertion (26 eyes) or ILM flap (23 eyes) technique. RESULTS: The MH closure rate at 12 months was greater in the ILM flap group versus the ILM insertion group (95% vs. 73%, respectively, P = 0.059). The postoperative best-corrected visual acuity (BCVA) at 12 months was significantly better in the ILM flap group (P = 0.014). All eyes (100%) showed an improvement in the BCVA of ≥0.3 logarithm of the minimum angle of resolution (15 Early Treatment Diabetic Retinopathy Study letters) in the ILM flap group versus 20 eyes (77%) in the ILM insertion group (P = 0.026). The preoperative BCVA and the ILM flap technique were significantly correlated with the postoperative BCVA (P = 0.028 and 0.027, respectively) and BCVA improvement (≥0.3 logarithm of the minimum angle of resolution [15 Early Treatment Diabetic Retinopathy Study letters]; P = 0.003 and 0.026, respectively). CONCLUSION: The inverted ILM flap technique was more effective in improving the postoperative BCVA in patients with MH-associated retinal detachment when compared with the ILM insertion technique. The preoperative BCVA and the ILM flap technique were independent prognostic factors for visual outcomes in patients with MH-associated retinal detachment.
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Membrana Basal/cirurgia , Macula Lutea/patologia , Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Retalhos Cirúrgicos , Tomografia de Coerência Óptica/métodos , Vitrectomia/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Perfurações Retinianas/complicações , Perfurações Retinianas/diagnóstico , Estudos RetrospectivosRESUMO
Purpose: Excessive angiogenesis, also known as neovascularization, has considerable pathophysiologic roles in several retinal diseases, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration. Accumulated evidence has revealed that miRNAs play important roles in endothelial cell dysfunction and angiogenesis. However, the role of microRNA-29b-3p (miR-29b-3p) in retinal angiogenesis is still unclear. Therefore, we investigated whether and how miR-29b-3p affects the function of retinal microvascular endothelial cells (RMECs). Methods: The overexpression and inhibition of miR-29b-3p were achieved by transfecting rat RMECs with an miR-29b-3p mimic and inhibitor, respectively. The proliferation, migration, and angiogenesis of RMECs were evaluated using a Cell Counting Kit-8 assay, Ki67 staining, western blotting (of proliferating cell nuclear antigen, cyclin A2, cyclin D1, and cyclin E1), wound healing test, and tube formation assay. The expression levels of vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor B (PDGFB) were examined with quantitative real-time PCR and western blotting, respectively. Results: Overexpression of miR-29b-3p statistically significantly inhibited the function of RMECs in cell proliferation and angiogenesis, while inhibition of miR-29b-3p increased the proliferative and angiogenic activities of RMECs. Moreover, VEGFA and PDGFB, as the targets of miR-29b-3p, were statistically significantly downregulated by the miR-29b mimic, whereas the miR-29b-3p inhibitor had the opposite effects. Conclusions: miR-29b-3p negatively regulates RMEC proliferation and angiogenesis, at least partly by targeting VEGFA and PDGFB. These data may provide a potential therapeutic strategy for treating ocular neovascular diseases.
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Proliferação de Células/genética , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Sobrevivência Celular/genética , Células Cultivadas , Regulação para Baixo , MicroRNAs/genética , Neovascularização Patológica/genética , Fator de Crescimento Derivado de Plaquetas/genética , Ratos , Transfecção , Regulação para Cima , Cicatrização/genéticaRESUMO
PURPOSE: To investigate the clinical characteristics and visual outcome of bilateral acute retinal necrosis. METHODS: The study included 30 patients (60 eyes) who were diagnosed with bilateral acute retinal necrosis. The medical records were reviewed. RESULTS: Twenty-five patients developed the disease in the contralateral eye within 5 months and 5 patients at >2 years after the initial onset. At presentation, 14 of 21 eyes suffered from retinal necrosis of more than 180° in the initially affected eye, whereas 3 of 22 eyes suffered it in the later-affected eye. Retinal detachment occurred in 23 of the 27 initially affected eyes and in 5 of the 27 later-affected eyes. The mean logarithm of the minimum angle of resolution best-corrected visual acuity decreased from 2.0 ± 1.1 (Snellen equivalent counting fingers) to 2.2 ± 1.0 (Snellen equivalent counting fingers) in the initially affected eyes after a follow-up of 34.1 ± 48.2 months (P = 0.529), and improved from 0.5 ± 0.4 (Snellen equivalent 20/66) to 0.3 ± 0.4 (Snellen equivalent 20/40) in the later-affected eyes after a follow-up of 21.2 ± 23.3 months (P = 0.005). CONCLUSION: Bilateral acute retinal necrosis usually occurs in the contralateral eye within a few months, but sometimes after several years. Inflammation and retinal necrosis are less severe in the later-affected eye, with less retinal detachment and a better visual outcome.
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Infecções Oculares Virais/virologia , Herpes Simples/virologia , Herpes Zoster Oftálmico/virologia , Síndrome de Necrose Retiniana Aguda/virologia , Aciclovir/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/tratamento farmacológico , Infecções Oculares Virais/fisiopatologia , Feminino , Ganciclovir/uso terapêutico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Herpes Simples/fisiopatologia , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/tratamento farmacológico , Herpes Zoster Oftálmico/fisiopatologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Síndrome de Necrose Retiniana Aguda/diagnóstico , Síndrome de Necrose Retiniana Aguda/tratamento farmacológico , Síndrome de Necrose Retiniana Aguda/fisiopatologia , Estudos Retrospectivos , Acuidade Visual , Vitrectomia , Adulto JovemRESUMO
PURPOSE: To demonstrate the anti-inflammatory action of a synthetic glucocorticoid-induced leucine zipper (GILZ98-134) peptide (GILZ-p) in a model of endotoxin-induced uveitis (EIU) in rats. METHODS: The EIU model was induced in Sprague Dawley rats with an intravitreal injection of lipopolysaccharide (LPS). Synthetic GILZ-p was injected intravitreally 6 h after the LPS injection. To evaluate the anti-inflammatory effects of GILZ-p, the inflammatory response in the anterior chamber and iris of the rat eyes was evaluated with a slitlamp microscope on days 0, 1, 2, 3, and 4 after GILZ-p injection. The retinal expression of inflammatory cytokines was measured on days 0, 1, 2, 3, and 4 after GILZ-p injection. Müller cell gliosis was also detected at planned time points after GILZ-p injection. RESULTS: Anterior segment inflammation peaked at 24 h after LPS injection in the EIU model. Compared with the controls, intravitreal GILZ-p significantly suppressed LPS-induced anterior segment inflammation in the EIU rats. The levels of retinal inflammatory factors IL-1ß, TNF-α, MCP-1, and ICAM-1 were simultaneously reduced by the intravitreal GILZ-p injection. The expression of vimentin in the EIU retina was significantly reduced by GILZ-p, and the downregulated aquaporin 4 in the EIU retina was significantly restored by GILZ-p. CONCLUSION: The synthetic GILZ-p inhibited the inflammatory reaction in the EIU model and may have utility in the treatment of inflammatory ocular disease.
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Inflamação/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Fatores de Transcrição/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Animais , Western Blotting , Citocinas/metabolismo , Modelos Animais de Doenças , Células Ependimogliais/efeitos dos fármacos , Gliose/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intravítreas , Lipopolissacarídeos/toxicidade , Masculino , Fragmentos de Peptídeos/síntese química , Ratos , Ratos Sprague-Dawley , Retina/metabolismo , Microscopia com Lâmpada de Fenda , Fatores de Transcrição/síntese química , Uveíte Anterior/induzido quimicamente , Uveíte Anterior/metabolismoRESUMO
OBJECTIVES: To investigate the clinical characteristics of acute retinal necrosis (ARN) with ultra-wide-field imaging (UWFI) and analyse their visual significance. METHODS: Clinical and UWFI records of patients diagnosed with ARN at a single centre over 2 years were reviewed. RESULTS: In 38 eyes of 35 patients, the clinical manifestations of ARN on UWFI included patchy (12 eyes) or fan-shaped necrotic lesions (26 eyes), retinal arterial obliteration (38 eyes), vitritis (38 eyes), retinal venous haemorrhage (19 eyes), and vitreous haemorrhage (6 eyes). Retinal detachment was associated with the number of retinal quadrants involved (ß = 2.145, P = 0.005). LogMAR BCVA at last follow-up was associated with logMAR BCVA at presentation (ß = 0.473, P = 0.004) and retinal detachment (ß = 0.367, P = 0.020). CONCLUSION: UWFI is useful for detecting retinal lesions in ARN, especially peripheral lesions or through opaque media, and provides valuable information concerning visual prognosis.
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Descolamento Retiniano , Síndrome de Necrose Retiniana Aguda , Fundo de Olho , Humanos , Retina/diagnóstico por imagem , Descolamento Retiniano/diagnóstico por imagem , Síndrome de Necrose Retiniana Aguda/diagnóstico por imagem , Estudos Retrospectivos , Hemorragia VítreaRESUMO
BACKGROUND: This study aimed to investigate the neuroprotective function of a synthesized glucocorticoid-induced leucine zipper peptide (GILZ-p) in a light-induced retinal degeneration model. METHODS: The GILZ98-134 peptide was synthesized and injected intravitreally into Sprague Dawley rats. Retinal injury was then induced in the rats by exposing their eyes to constant white light (5000 lux) for 24 h. The activation of retinal caspases-9/3 and the release of cytochrome c from the mitochondria to the cytosol were measured at 1, 3, 5 and 7 d after light injury. Photoreceptor apoptosis was evaluated with terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining at 3 d after injury. Haematoxylin and eosin staining and electroretinography were used to observe the changes in the retinal morphology and function, respectively, at 7 and 14 d after light injury. RESULTS: The intravitreally injected synthesized GILZ-p successfully penetrated to the retina and significantly inhibited the activation of retinal caspase-3 and caspase-9 at 1, 3, 5 and 7 d after light injury, and reduced the number of TUNEL-positive photoreceptors at 3 d after light injury. GILZ-p pre-treatment also alleviated cytochrome c release and rescued mitochondria-mediated apoptosis after injury. Simultaneously, GILZ-p pre-treatment also mitigated the light-induced thinning of the outer nuclear layer and the loss of retinal function at 7 and 14 d after light injury, respectively. CONCLUSIONS: The synthesized GILZ-p prevented light-induced photoreceptor apoptosis and protected retinal function from degeneration, and is therefore a potential therapeutic option for degenerative retinal diseases.
Assuntos
Apoptose/efeitos dos fármacos , Luz/efeitos adversos , Células Fotorreceptoras de Vertebrados/fisiologia , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Degeneração Retiniana/prevenção & controle , Fatores de Transcrição/farmacologia , Animais , Western Blotting , Eletrorretinografia , Células Ependimogliais/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Injeções Intravítreas , Zíper de Leucina , Masculino , Fragmentos de Peptídeos/síntese química , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/fisiopatologia , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/etiologia , Degeneração Retiniana/fisiopatologia , Fatores de Transcrição/síntese química , Fatores de Transcrição/fisiologiaRESUMO
PURPOSE: To describe the characteristics of retinal telangiectasia in eyes with pathologic myopia. METHODS: The study included 10 patients (18 eyes) who were diagnosed with pathologic myopia combined with retinal telangiectasia. The patients visited our retinal clinic every 3 months. Nine eyes underwent vitrectomy for vision-threatening complications after diagnosis. All eyes underwent comprehensive ophthalmologic examinations including multimodal retinal imaging at presentation and at each follow-up. RESULTS: Retinal telangiectasia in pathologic myopia was characterized by saccular aneurysmal dilatation of the capillary bed without hard exudates in color fundus photographs and hyporeflective saccular structure in infrared reflectance fundus photographs, and it was filled in the early retinal arteriovenous phase with minimal dye leakage in the late phase of fundus fluorescein angiography. Spectral domain optical coherence tomography and optical coherence tomographic angiography showed that retinal telangiectasia was primarily located in the superficial retina, together with myopic traction maculopathy. In the 9 eyes that underwent vitrectomy, the retinal telangiectasia regressed within 3 months of surgery. Retinal telangiectasia remained stable in the other nine eyes, but these eyes were at risk of spontaneous bleeding. CONCLUSION: Retinal telangiectasia is a relatively quiescent and uncommon disorder in patients with pathologic myopia that might be closely related to myopic traction maculopathy.
Assuntos
Miopia Degenerativa/diagnóstico , Telangiectasia Retiniana/diagnóstico , Adulto , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Miopia Degenerativa/fisiopatologia , Miopia Degenerativa/cirurgia , Estudos Prospectivos , Retina/patologia , Telangiectasia Retiniana/fisiopatologia , Telangiectasia Retiniana/cirurgia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Vitrectomia , Adulto JovemRESUMO
Purpose: To summarize the characteristics of endogenous fungal endophthalmitis (EFE) after genitourinary procedures. Methods: Medical records of patients diagnosed with EFE after genitourinary procedures from a single center during a 6-year period were reviewed. Results: Nineteen eyes of 15 patients were included. The interval time between procedure to symptom was 3.6 ± 3.6 weeks. As the initial treatment, 9/19 eyes underwent primary vitrectomy and 10/19 eyes underwent intravitreal antifungal injection . Candida albicans was the pathogen in 15 of 19 eyes. Systemic treatment with itraconazole was used in all patients. LogMAR best corrected visual acuity improved from 2.2 ± 0.9 to 0.9 ± 1.2 after treatment (p = 0.002) in 15 eyes that were followed-up for an average of 4.9 ± 2.1 years. Conclusion: Genitourinary procedure is a predisposing factor for EFE. Candida albicans is the predominant pathogen. Normative systemic and local antifungal treatments improved the final visual outcome.
Assuntos
Endoftalmite/etiologia , Infecções Oculares Fúngicas/etiologia , Doenças Urogenitais Femininas/cirurgia , Doenças Urogenitais Masculinas/cirurgia , Adulto , Idoso , Antifúngicos/uso terapêutico , Endoftalmite/tratamento farmacológico , Endoftalmite/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Purpose: Lipocalin 2 (LCN2) is reported to be one of the key regulators of cell survival and death; however, its effect on retinal degeneration is unclear. Therefore, we aimed to investigate the role of LCN2 and its underlying mechanisms in light-induced retinal degeneration. Methods: A recombinant lentivirus expressing a short hairpin RNA targeting LCN2 mRNA and a recombinant lentivirus overexpressing LCN2 were used to downregulate and upregulate retinal LCN2, respectively. Seven days after intravitreal injection of the lentiviruses, rats were exposed to blue light (2500 lux) for 24 hours. Retinal function and morphology were evaluated with ERG and hematoxylin-eosin staining, respectively. TUNEL staining was used to detect apoptotic cells. The levels of reactive oxygen species (ROS) were evaluated with dihydroethidium labeling. Western blotting and real-time PCR were used to examine protein and mRNA expression levels, respectively. Results: Retinal LCN2 expression was significantly upregulated after light exposure. Light exposure reduced the amplitudes of a- and b-waves on the ERG and the thickness of the outer nuclear layer and promoted photoreceptor apoptosis. These phenomena were clearly attenuated by LCN2 knockdown, whereas LCN2 overexpression had the opposite effects. The overexpression of LCN2 facilitated photoreceptor apoptosis by increasing ROS generation and Bim expression. On the opposite, LCN2 knockdown mitigated the generation of light-exposure-induced ROS and the activation of the Bim-mediated mitochondrial apoptotic pathway. Conclusions: Light-induced LCN2 is a proapoptotic factor in the retina, and LCN2 knockdown protects photoreceptors from apoptosis by inhibiting ROS production and Bim expression. LCN2 is a potential therapeutic target for light-induced retinal degeneration.
Assuntos
Apoptose , Proteína 11 Semelhante a Bcl-2/metabolismo , Luz/efeitos adversos , Lipocalina-2/fisiologia , Lesões Experimentais por Radiação/patologia , Espécies Reativas de Oxigênio/metabolismo , Retina/efeitos da radiação , Degeneração Retiniana/patologia , Animais , Western Blotting , Regulação para Baixo , Eletrorretinografia , Marcação In Situ das Extremidades Cortadas , Injeções Intravítreas , Lentivirus/genética , Masculino , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Lesões Experimentais por Radiação/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Retina/fisiopatologia , Degeneração Retiniana/metabolismo , Transdução de Sinais/fisiologia , Regulação para CimaRESUMO
Purpose: The anti-inflammatory activities of protein glucocorticoid-induced leucine zipper (GILZ) have been demonstrated in vivo and in vitro. Here, we examined the potential effect of a synthetic peptide derived from the leucine zipper motif and proline-rich region of GILZ on suppressing inflammatory responses in primary cultured rat Müller cells. Methods: Peptides were selected from amino acids 98-134 of the GILZ protein (GILZ-p). Solid-phase peptide synthesis was used to generate the cell-penetrating peptide TAT, which was bound to the amino terminus of GILZ-p. Primary cultured retinal Müller cells were stimulated with lipopolysaccharide (LPS) alone or in combination with different concentrations of GILZ-p, and the interaction of GILZ-p with nuclear factor (NF)-κB p65 in Müller cells was investigated by western blotting, immunoprecipitation, and immunofluorescence. The expression of the Müller cell gliosis marker glial fibrillary acidic protein (GFAP), functional protein aquaporin (AQP)-4, and the inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF) α, intercellular adhesion molecule (ICAM)-1, and monocyte chemoattractant protein (MCP)-1 was measured by Western Blotting. The concentration of those cytokines in culture medium was measured by using Enzyme-Linked Immunosorbent Assay. Results: The synthesized GILZ-p, which was water-soluble, entered cells and bound with NF-κB p65, inhibiting p65 nuclear translocation. GILZ-p inhibited the LPS-induced expression of GFAP, IL-1ß, TNFα, ICAM-1, and MCP-1 in Müller cells and prevented the LPS-induced downregulation of AQP4. Conclusions: These results indicate that GILZ-p interacted with NF-κB p65 and suppressed p65 nuclear translocation, thereby inhibiting inflammatory cytokine release and Müller cell gliosis.