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PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Vacinas contra COVID-19 , COVID-19 , Oclusão da Artéria Retiniana , Oclusão da Veia Retiniana , Feminino , Humanos , Masculino , Vacina de mRNA-1273 contra 2019-nCoV , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Teste para COVID-19 , Vacinas contra COVID-19/efeitos adversos , Artéria Retiniana , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/complicações , Oclusão da Veia Retiniana/epidemiologia , Oclusão da Veia Retiniana/etiologia , Oclusão da Veia Retiniana/diagnóstico , Vacinação/efeitos adversosRESUMO
PURPOSE: To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion. DESIGN: Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192). PARTICIPANTS: Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO. METHODS: Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24 weeks. MAIN OUTCOME MEASURES: Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug. RESULTS: Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change, +16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs. +17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs. +17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 µm [95.03% CI, -316.4 to -306.4 µm] and -304.4 µm [95.03% CI, -309.3 to -299.4 µm]) and COMINO (-461.6 µm [95.03% CI, -471.4 to -451.9 µm] and -448.8 µm [95.03% CI, -458.6 to -439.0 µm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P = 0.0023) and COMINO (44.4% vs. 30.0%; nominal P = 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n = 45] and 23.0% [n = 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n = 56] and 27.7% [n = 100], respectively). CONCLUSIONS: These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Inibidores da Angiogênese , Injeções Intravítreas , Edema Macular , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Oclusão da Veia Retiniana , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Edema Macular/fisiopatologia , Edema Macular/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/fisiopatologia , Acuidade Visual/fisiologia , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Masculino , Feminino , Método Duplo-Cego , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Angiopoietina-2/antagonistas & inibidoresRESUMO
PURPOSE: To measure non-invasively retinal venous blood flow (RBF) in healthy subjects and patients with retinal venous occlusion (RVO). METHODS: The prototype named AO-LDV (Adaptive Optics Laser Doppler Velocimeter), which combines a new absolute laser Doppler velocimeter with an adaptive optics fundus camera (rtx1, Imagine Eyes®, Orsay, France), was studied for the measurement of absolute RBF as a function of retinal vessel diameters and simultaneous measurement of red blood cell velocity. RBF was measured in healthy subjects (n = 15) and patients with retinal venous occlusion (RVO, n = 6). We also evaluated two softwares for the measurement of retinal vessel diameters: software 1 (automatic vessel detection, profile analysis) and software 2 (based on the use of deep neural networks for semantic segmentation of vessels, using a M2u-Net architecture). RESULTS: Software 2 provided a higher rate of automatic retinal vessel measurement (99.5 % of 12,320 AO images) than software 1 (64.9 %) and wider measurements (75.5 ± 15.7 µm vs 70.9 ± 19.8 µm, p < 0.001). For healthy subjects (n = 15), all the retinal veins in one eye were measured to obtain the total RBF. In healthy subjects, the total RBF was 37.8 ± 6.8 µl/min. There was a significant linear correlation between retinal vessel diameter and maximal velocity (slope = 0.1016; p < 0.001; r2 = 0.8597) and a significant power curve correlation between retinal vessel diameter and blood flow (3.63 × 10-5 × D2.54; p < 0.001; r2 = 0.7287). No significant relationship was found between total RBF and systolic and diastolic blood pressure, ocular perfusion pressure, heart rate, or hematocrit. For RVO patients (n = 6), a significant decrease in RBF was noted in occluded veins (3.51 ± 2.25 µl/min) compared with the contralateral healthy eye (11.07 ± 4.53 µl/min). For occluded vessels, the slope between diameter and velocity was 0.0195 (p < 0.001; r2 = 0.6068) and the relation between diameter and flow was Q = 9.91 × 10-6 × D2.41 (p < 0.01; r2 = 0.2526). CONCLUSION: This AO-LDV prototype offers new opportunity to study RBF in humans and to evaluate treatment in retinal vein diseases.
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Oclusão da Veia Retiniana , Veia Retiniana , Humanos , Oclusão da Veia Retiniana/diagnóstico , Fluxo Sanguíneo Regional , Retina , Vasos Retinianos , Angiofluoresceinografia/métodos , Veia Retiniana/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Fluxometria por Laser-DopplerRESUMO
Retinal neovascularization (RNV) is a pathological process that primarily occurs in diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. It is a common yet debilitating clinical condition that culminates in blindness. Urgent efforts are required to explore more efficient and less limiting therapeutic strategies. Key RNA-binding proteins (RBPs), crucial for post-transcriptional regulation of gene expression by binding to RNAs, are closely correlated with RNV development. RBP-RNA interactions are altered during RNV. Here, we briefly review the characteristics and functions of RBPs, and the mechanism of RNV. Then, we present insights into the role of the regulatory network of RBPs in RNV. HuR, eIF4E, LIN28B, SRSF1, METTL3, YTHDF1, Gal-1, HIWI1, and ZFR accelerate RNV progression, whereas YTHDF2 and hnRNPA2B1 hinder it. The mechanisms elucidated in this review provide a reference to guide the design of therapeutic strategies to reverse abnormal processes.
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Proteínas de Ligação a RNA , Neovascularização Retiniana , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação da Expressão Gênica/fisiologia , AnimaisRESUMO
The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.
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OBJECTIVES: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients. METHODS: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed. RESULTS: The automatic MPCLEIA system was able to provide results in 45â¯min with only 20⯵L sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26â¯ng/L, 23.57â¯ng/L, 1,110.12â¯ng/L, 105.52â¯ng/L, and 85.39â¯ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25â¯% or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category. CONCLUSIONS: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.
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Edema Macular , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Sistemas Automatizados de Assistência Junto ao Leito , Interleucina-8 , Edema Macular/diagnóstico , Edema Macular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Interleucina-6 , Humor Aquoso/metabolismoRESUMO
PURPOSE: To investigate the combined association of the ischemic index and leakage index with macular edema on ultra-widefield fluorescein angiography (UWFFA) in patients with branch retinal vein occlusion (BRVO). METHODS: Retrospective image analysis study. The leakage index and ischemic index were calculated using Fiji after aligning early and late UWFFA images. Differences in the ischemic index, leakage index, and central macular thickness (CMT) between ischemic and non-ischemic BRVO were compared. Moreover, the association between the ischemic index, leakage index, and macular edema was analyzed. RESULTS: Eighty-three patients with BRVO were enrolled, including 53 non-ischemic BRVO and 30 ischemic BRVO patients. No significant differences were observed in leakage index and CMT between ischemic BRVO and non-ischemic BRVO (all P > 0.05). In all included patients, CMT correlated with the panretina and all subregion leakage indexes (all P < 0.01), but not with the ischemic index (all P > 0.05). In the ischemic BRVO group, CMT showed a correlation with the leakage index in several regions, but not with the ischemic index. After adjusting for the ischemic index and other clinical features, CMT remained significantly correlated with the leakage index in all regions. CONCLUSION: The leakage index may be a more effective biomarker for monitoring BRVO-associated macular edema compared to the ischemic index. Further follow-up studies are warranted to validate these findings.
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Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Edema Macular/diagnóstico , Edema Macular/etiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodosRESUMO
BACKGROUND: To investigate the association between the triglyceride-glucose (TyG) index and newly diagnosed branch retinal vein occlusion (BRVO) in patients. METHODS: The study included 57 individuals with BRVO and a control group comprising 50 healthy volunteers matched for age and gender. Detailed eye examinations were conducted, and various blood biochemistry and hematological parameters were recorded. The TyG index was calculated using fasting plasma glucose and triglyceride values. RESULTS: The mean age was 61.4 ± 9.6 years for the BRVO group and 60.6 ± 10.3 years for the control group. The TyG values were significantly higher in the BRVO group when compared to the control group (8.84 ± 0.41 vs. 8.52 ± 0.29, p < 0.001). Multivariate analysis revealed that the TyG index independently predicted BRVO (odds ratio = 2.58, 95% confidence interval = 1.69-3.93; p < 0.001). In receiver operating characteristics analysis, the TyG index had an area under the curve of 0.749, and a TyG index higher than 8.52 predicted BRVO with 83% sensitivity and 70% specificity. CONCLUSIONS: This study establishes a significant association between an elevated TyG index and BRVO. Consequently, the TyG index could serve as a valuable predictive tool for identifying individuals at risk for BRVO.
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Glicemia , Curva ROC , Oclusão da Veia Retiniana , Triglicerídeos , Humanos , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Glicemia/metabolismo , Biomarcadores/sangue , Fatores de Risco , Idoso , Angiofluoresceinografia/métodosRESUMO
PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.
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Inibidores da Angiogênese , Ranibizumab , Oclusão da Veia Retiniana , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiologia , Edema Macular/fisiopatologia , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/fisiopatologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
PURPOSE: To investigate associations between contrast sensitivity (CS) and vascular metrics on wide-field swept-source optical coherence tomography angiography (WF-SS-OCTA) in patients with retinal vein occlusion (RVO). METHODS: This prospectively recruited, cross-sectional observational study included RVO patients who underwent quantitative CS function (qCSF) testing and WF-SS-OCTA using 3 × 3, 6 × 6, and 12 × 12 mm angiograms on the same day. The study measured several qCSF outcomes and WF-SS-OCTA vascular metrics, including vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ). The data were analyzed using multivariable regression analysis controlling for age and central subfield thickness (CST). RESULTS: A total of 43 RVO eyes of 43 patients and 30 fellow eyes were included. In RVO eyes, multiple vascular metrics were associated with CS outcomes but not visual acuity (VA). On 12 × 12 images, CS thresholds at 1 cpd, 1.5 cpd, and 3 cpd were significantly associated with VD and VSD, but VA was not. When comparing standardized regression coefficients, we found that vascular metrics had a larger effect size on CS than on VA. For instance, the standardized beta coefficient for FAZ area and CS at 6 cpd (ß* = - 0.46, p = 0.007) was larger than logMAR VA (ß* = 0.40, p = 0.011). CONCLUSION: Microvascular changes on WF-SS-OCTA in RVO had a larger effect size on CS than VA. This suggests CS may better reflect the microvascular changes of RVO compared to VA. qCSF-measured CS might be a valuable adjunct functional metric in evaluating RVO patients.
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Macula Lutea , Oclusão da Veia Retiniana , Humanos , Sensibilidades de Contraste , Oclusão da Veia Retiniana/diagnóstico , Tomografia de Coerência Óptica , Estudos Transversais , AngiografiaRESUMO
BACKGROUND: We aimed to investigate the effect of retinal vein occlusion (RVO) on the posterior segment structures of the eye and its changes with intravitreal anti-Vascular Endothelial Growth Factor (VEGF) treatment. METHODS: This prospective longitudinal study included 29 eyes of 29 patients with RVO (17 males and 12 females) followed for 6 months. The best corrected visual acuity (BCVA), macula, choroid ticknesses and choroidal vascularity index (CVI) obtained by spectral-domain optical coherence tomography were recorded at baseline and the first, third, and sixth months after the first injection. Results were compared with fellow eyes (non-affected eyes) and age- and sex-matched controls. RESULTS: BCVA increased significantly in the 6th month, more in the first month of injection (p < 0.05 for each). Central macular tickness, subfoveal choroid tickness, stromal and total area of choroid decreased significantly after injection (p < 0.05 for each). CVI values increased significantly, especially in the 1st month after injection (p < 0.05 for each). In eyes with Branch RVO, there was a significant decrease in the macular thickness of the occlusive areas with treatment, while there was no statistically significant change in the non-occlusive macular thickness. CONCLUSION: Observation of changes in choroidal structure may be useful to assess the activity of RVO and predict the efficacy of anti-VEGF therapy.
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BACKGROUND: Central serous chorioretinopathy (CSC) has frequently been associated with increased stress levels as well as an increased prevalence of other psychiatric conditions. This study used standardized psychometric scores to assess stress, depression and anxiety levels of CSC patients and compared them to controls without retinal disease ("healthy") and with branch retinal vein occlusion (BRVO). METHODS: Monocentric, longitudinal case control study on consecutive CSC patients seen at a tertiary referral center. Controls without retinal disease were recruited from the oculoplastics clinic and those with BRVO from the medical retina clinic. Patients completed pseudonymized tests measuring stress levels (PHQ-stress), depression (PHQ-9) and anxiety (GAD-7) at baseline and at 3- and 6-months follow-up. Higher scores indicated higher trait levels. RESULTS: 65 CSC patients, 19 healthy controls and 19 BRVO patients were included in this study. CSC patients showed significantly higher stress levels at baseline compared to controls (p = 0.009), but not compared to BRVO patients (p = 1.00). At 3- and 6-months follow-up, no significant difference between groups was observed anymore. Acute CSC patients showed higher scores than those with chronic CSC, which also subsided over time. Depression and anxiety scores did not differ between groups at any timepoint. CONCLUSIONS: Patients with CSC do not show higher initial stress levels than patients with BRVO, while anxiety and depression levels did not differ from controls. Stress may thus rather represent a consequence of the onset of visual deterioration observed in CSC or other ocular diseases.
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Coriorretinopatia Serosa Central , Humanos , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/complicações , Estudos de Casos e Controles , Psicometria , Retina , Tomografia de Coerência Óptica , AngiofluoresceinografiaRESUMO
BACKGROUND: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea. METHODS: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates. RESULTS: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years. CONCLUSION: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion.
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Oclusão da Artéria Retiniana , Oclusão da Veia Retiniana , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Incidência , Oclusão da Veia Retiniana/diagnóstico , Estudos de Coortes , Oclusão da Artéria Retiniana/diagnóstico , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: To analyze the clinical features of refractory cystoid macular edema related to retinal vein occlusion associated with the response to three consecutive loading doses of anti-vascular endothelial growth factor. METHODS: A retrospective chart review was performed on retinal vein occlusion patients treated by three anti-vascular endothelial growth factor injections. They were divided into a group according to resolution of macular edema in optical coherence tomography (Group 1) and with persistent macular edema (Group 2). We analyzed qualitative and quantitative morphologic features of optical coherence tomography. RESULTS: We enrolled a total of 120 eyes from 120 patients (Group 1: n = 54, Group 2: n = 66). The baseline choroidal thickness differed significantly between groups 1 and 2 (290.70 ± 19.58 µm and 311.06 ± 17.87 µm P < 0.001). The presence of Hyperreflective foci (16.70% vs. 36.40% P < 0.001), Disorganization of the retinal inner layers (14.80% vs. 87.90%) and external limiting membrane disruption (16.60% vs. 39.3% P < 0.001) differed significantly. Logistic regression analysis showed that the initial central macular thickness (B = 0.012; P = 0.006), baseline choroidal thickness (B = 0.232; P = 0.016) and presence of hyperreflective foci (B = 1.050; P = 0.019), disorganization of the retinal inner layers (B = 1.132; P = 0.001) and external limiting membrane disruption (B = 1.575; P = 0.012) significantly affected the anti-vascular endothelial growth factor treatment response. CONCLUSION: A thicker sub-fovea choroid and the presence of hyperreflective foci, disruption of the external limiting membrane and disorganization of the retinal inner layers associated with a poorer response to three loading anti-vascular endothelial growth factor injections in macular edema associated retinal vein occlusion.
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Bevacizumab , Edema Macular , Oclusão da Veia Retiniana , Humanos , Fatores de Crescimento Endotelial , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retina , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Bevacizumab/uso terapêuticoRESUMO
BACKGROUND: Frosted branch angiitis is a retinal vascular condition that is associated with a viral infection or autoimmune disorders like Crohn's disease, systemic lupus erythematosus, and Behcet's disease. Frosted branch angiitis presents with vascular inflammation, retinal edema, and severe retinal vascular sheathing. We present a case of systemic juvenile idiopathic arthritis, an autoinflammatory disease, presenting with frosted branch angiitis. REPORT OF CASE: A 14-year-old female with systemic juvenile idiopathic arthritis and a history of bilateral anterior uveitis developed acute unilateral vision loss and was found to have frosted branch angiitis complicated by branch retinal vein occlusion. She underwent an extensive serology workup and aqueous viral PCR to rule out other possible autoimmune and viral etiologies for forested branch angiitis. She received systemic and intravitreal antiviral treatment due to positive CMV IgM initially. However, the clinical picture improved following the use of a higher dose of oral steroids and the switch of the immunosuppressive agent to a TNF-a inhibitor. CONCLUSION: To our knowledge, this would be the first case in the literature demonstrating a systemic juvenile idiopathic arthritis patient presenting with frosted branch angiitis. Infectious causes still must be ruled out, especially CMV, as it is the most common cause of secondary frosted branch angiitis.
Assuntos
Artrite Juvenil , Síndrome de Behçet , Infecções por Citomegalovirus , Doenças Retinianas , Vasculite , Feminino , Humanos , Adolescente , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: The most feared complication of intravitreal injections is the development of endophthalmitis, which could lead to irreversible visual loss. The aim of this study was to characterize the clinical profiles, causative pathogens, and clinical outcome of patients post-endophthalmitis. METHODS: Retrospective, single center case series study. Clinical records, causative pathogens and management of all cases of endophthalmitis post intravitreal anti-vascular endothelial growth factor (VEGF) injections recorded between January 1st, 2006 and May 30th, 2022; were retrieved. The visual and anatomic changes prior to the episode of endophthalmitis and up to 2 years post-treatment were compared. RESULTS: Eleven post-injection endophthalmitis eyes of 10 patients (n = 3 females; 30%) were recruited at mean age of 64.5 ± 20.4 years. The median last recorded BCVA, up to 3 months prior to the episode of endophthalmitis was 60 (Interquartile range (IQR) 55-75) ETDRS letters. Then, it dropped to 30 (IQR 0-57.5), 35 (IQR 0-52.5) and 35 (IQR 0-57.5) ETDRS letters at presentation, 6- and 12-months follow-up; respectively (p = 0.027, p = 0.017 and p = 0.012). However, at 24 months, the median BCVA returned to similar baseline values prior to the episode of endophthalmitis; BCVA 50 (IQR 0-60) ETDRS letters, p = 0.062. Interestingly, two eyes with neovascular age-related macular degeneration (NVAMD), 1 with myopic choroidal neovascularization (CNV) and 1 with retinal vein occlusion (RVO), experienced disease quiescence and did not require additional anti-VEGF injections up to 2 years of follow-up. CONCLUSION: This study demonstrates long-term recovery of vision loss due to endophthalmitis post anti-VEGF injections, regained up to 2 years later. It also indicates that disease quiescence post endophthalmitis may not only occur in eyes treated for NVAMD, but also with myopic CNV and RVO.
Assuntos
Neovascularização de Coroide , Endoftalmite , Oclusão da Veia Retiniana , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Ranibizumab/uso terapêutico , Inibidores da Angiogênese , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Estudos Retrospectivos , Oclusão da Veia Retiniana/tratamento farmacológico , Neovascularização de Coroide/tratamento farmacológico , Injeções Intravítreas , Endoftalmite/etiologia , Endoftalmite/complicaçõesRESUMO
BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.
Assuntos
Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteômica/métodos , Fibrinogênio/uso terapêuticoRESUMO
BACKGROUND: The study was designed to investigate microvascular and morphological changes in retinal vein occlusion (RVO) using multimodal imaging after intravitreal ranibizumab (IVR) with or without triamcinolone acetonide (IVTA) injections. METHODS: This was a retrospective and observational study. Fifty patients (52 eyes) diagnosed with RVO were enrolled. Best corrected visual acuity (BCVA), ophthalmoscopy, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SDOCT), and optical coherence tomography angiography (OCTA) were employed sequentially both before treatment and at the last visit after treatment. RESULTS: The mean logMAR VAs in BRVO eyes decreased significantly after treatment (P = 0.029). OCTA showed there was a significant difference in foveal avascular zone (FAZ) in BRVO eyes (P = 0.024), superificial foveal vessel density in both CRVO (P = 0.0004) and BRVO eyes (P = 0.02155). OCT showed the foveal thickness had significant differences after treatment in both CRVO (P < 0.0001) and BRVO eyes (P = 0.0001). BCVA was associated most commonly with ellipsoid zone integrity (P = 0.022). The BCVA in eyes treated with IVR and IVTA was significantly decreased compared with IVR only in BRVO group (P = 0.021). However, the combination of IVR + IVTA significantly improved intraocular pressure (IOP) compared with IVR only in BRVO group (P = 0.037). CONCLUSION: Both IVR and IVR + IVTA can significantly improve the central vision, macular structure, and functions in BRVO group. Simultaneous IVR with IVTA can significantly increase BCVA compared with IVR only in BRVO group.
Assuntos
Inibidores da Angiogênese , Angiofluoresceinografia , Glucocorticoides , Injeções Intravítreas , Imagem Multimodal , Ranibizumab , Oclusão da Veia Retiniana , Tomografia de Coerência Óptica , Triancinolona Acetonida , Acuidade Visual , Humanos , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/fisiopatologia , Estudos Retrospectivos , Masculino , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/uso terapêutico , Feminino , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Tomografia de Coerência Óptica/métodos , Pessoa de Meia-Idade , Angiofluoresceinografia/métodos , Glucocorticoides/uso terapêutico , Glucocorticoides/administração & dosagem , Idoso , Vasos Retinianos/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/efeitos dos fármacos , Quimioterapia CombinadaRESUMO
BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.
Assuntos
Inibidores da Angiogênese , Anti-Inflamatórios não Esteroides , Benzofenonas , Bromobenzenos , Fator A de Crescimento do Endotélio Vascular , Humanos , Administração Tópica , Inibidores da Angiogênese/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Benzofenonas/administração & dosagem , Bromobenzenos/administração & dosagem , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
BACKGROUND: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. OBJECTIVES: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. METHODS: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. RESULTS: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = -4.75 ETDRS letters, 95% CI = [-7.73, -1.78], p = 0.002) and reduction in retinal thickness (WMD = -93.02 µm, 95% CI = [-153.23, -32.82], p = 0.002) at months 4-6 compared to low-dose (1-2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. CONCLUSIONS: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4-6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.