RESUMO
PURPOSE: To report real-world experiences on driving vision in patients with neovascular age-related macular degeneration (AMD) undergoing intravitreal anti-VEGF treatment. METHODS: Retrospective cohort study of treatment-naïve patients with neovascular AMD commenced in anti-VEGF treatment (n = 416) and followed for 4 years in a pro re nata treatment regimen. Monocular best-corrected visual acuity (BCVA) measured using ETDRS was performed on the treatment eye at all visits and on the fellow eye at baseline, every 6 months, and upon any patient-reported change in vision. Driving vision was defined as BCVA in the best-seeing eye of ≥70 ETDRS letters (equivalent to ≥0.5 Snellen) corresponding to the minimum BCVA required in many countries. RESULTS: Driving vision was present in 280 patients (67%) and was sustained in 86%, 74%, 65% and 59% of the patients at 1, 2, 3 and 4 years, respectively. Lower BCVA in the best-seeing eye predicted loss of driving vision. In patients without driving vision at baseline, driving vision was regained in 29%, 36%, 39% and 41% of the patients at 1, 2, 3 and 4 years, respectively; but only 35% sustained driving vision after the first year. Lower age and higher BCVA in best-seeing eye predicted regain of driving vision. CONCLUSION: Driving vision can be sustained in the majority of the patients if they have driving vision at baseline. This study provides important prognostic information for patients with neovascular AMD.
Assuntos
Condução de Veículo , Ranibizumab/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnósticoRESUMO
Purpose: Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive disease with no treatment option. Previous studies show chemokine-mediated recruitment of immune cells in the retina, and therefore we investigated systemic levels of chemokines and chemokine receptors in patients with GA. Methods: This observational prospective study was conducted at a single center. We included 122 participants with no immune disease: 41 participants with GA and no choroidal neovascularization, 51 patients with neovascular AMD, and 30 healthy control individuals. Flow cytometric analysis was used to detect expression level of C-C chemokine receptor (CCR)1, CCR2, CCR3, CCR5, and C-X-C motif chemokine receptor (CXCR)3 on peripheral blood mononuclear cells (CD14+ monocytes, CD4+ T cells, CD8+ T cells). Plasma levels of C-C motif ligand (CCL)11, C-X-C motif chemokine (CXCL)10, and CCL5 were measured by specific immunoassays. Enlargement rate of GA lesion was measured from autofluorescence images. Results: Participants with GA have a specific chemokine profile with a higher expression of CCR5 than healthy controls in peripheral blood mononuclear cells, and a higher plasma levels of CCL-5. Further, GA was associated with higher monocytic expression of CCR2 than in neovascular AMD. We found that a high expression level of CCR5 on CD8+ T cells was associated with slower enlargement rate of atrophic lesion. Conclusions: The study showed an association between systemic chemokine profile and GA formation. Further studies are needed to fully elucidate the possible role of systemic chemokine regulation in mediating pathogenesis of GA.
Assuntos
Quimiocina CCL5/genética , Regulação da Expressão Gênica , Atrofia Geográfica/genética , Receptores CCR5/genética , Degeneração Macular Exsudativa/genética , Idoso , Estudos de Casos e Controles , Neovascularização de Coroide/genética , Feminino , Atrofia Geográfica/diagnóstico , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Purpose: Geographic atrophy (GA) is a clinical phenotype of late age-related macular degeneration (AMD) with no current treatment available. In this study, we investigated markers of chronic inflammation in plasma of patients with GA and how these relate to progression rate. Methods: We prospectively included 42 patients with GA, 41 patients with neovascular AMD, and 27 healthy controls. We quantified levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF) receptor 2, and C-reactive protein (CRP). We adapted an inflammation summary score to cluster conceptually related markers of chronic inflammation. Enlargement rate of the atrophic lesion was measured from fundus autofluorescence images performed at baseline and after 1 year. Results: Patients with GA showed an increase in proinflammatory markers of IL-6 (P = 0.009), TNF receptor 2 (P = 0.013), and CRP (P = 0.017) compared to healthy controls. We found that IL-8 levels were markedly higher in patients with GA when compared to patients with neovascular AMD (P = 0.013). The inflammation summary score was high in patients with neovascular AMD (P = 0.024), but even higher in patients with GA (<0.001), when compared to healthy controls. GA enlargement was measured in 36 patients, who completed follow-up. Plasma levels of IL-6 had a moderate but significant correlation with GA enlargement rate (R2 = 0.23, P = 0.0035). Conclusions: Markers of chronic inflammation strongly associates with presence of GA secondary to AMD. Plasma IL-6 possesses predictive ability of progression and constitutes the first known plasma biomarker of disease activity in GA. These findings shed light into a poorly understood clinical phenotype of AMD and highlights the important role of chronic inflammation in GA.
Assuntos
Biomarcadores/sangue , Atrofia Geográfica/sangue , Atrofia Geográfica/diagnóstico , Interleucina-6/sangue , Degeneração Macular Exsudativa/complicações , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Progressão da Doença , Feminino , Angiofluoresceinografia , Técnicas de Genotipagem , Atrofia Geográfica/etiologia , Humanos , Interleucina-8/sangue , Masculino , Estudos Prospectivos , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Acuidade VisualRESUMO
Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One of the ligands for CFH is long pentraxin 3 (PTX3), which is produced locally in the retinal pigment epithelium (RPE). To test the hypothesis that PTX3 is relevant to retinal immunohomeostasis and may be associated with AMD pathogenesis, we measured plasma PTX3 protein concentration and analyzed the RPE/choroid PTX3 gene expression in patients with AMD. To measure the ability of RPE cells to secrete PTX3 in vitro, polarized ARPE-19 cells were treated with activated T cells or cytokines (interferon (IFN)-gamma and/or tumor necrosis factor (TNF)-alpha) from the basolateral side; then PTX3 protein concentration in supernatants and PTX3 gene expression in tissue lysates were quantified. Plasma levels of PTX3 were generally low and did not significantly differ between patients and controls (P=0.307). No statistically significant difference was observed between dry and exudative AMD nor was there any correlation with hsCRP or CFH genotype. The gene expression of PTX3 increased in RPE/choroid with age (P=0.0098 macular; P=0.003 extramacular), but did not differ between aged controls and AMD patients. In vitro, ARPE-19 cells increased expression of the PTX3 gene as well PTX3 apical secretions after stimulation with TNF-alpha or activated T cells (P<0.01). These findings indicate that PTX3 expressed in the eye cannot be detected systemically and systemic PTX3 may have little or no impact on disease progression, but our findings do not exclude that locally produced PTX3 produced in the posterior segment of the eye may be part of the AMD immunopathogenesis.
Assuntos
Proteína C-Reativa/metabolismo , Degeneração Macular/sangue , Componente Amiloide P Sérico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/genética , Estudos de Casos e Controles , Plexo Corióideo/metabolismo , Técnicas de Cocultura , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina/metabolismo , Componente Amiloide P Sérico/genéticaRESUMO
PURPOSE: We have recently identified homeostatic alterations in the circulating T cells of patients with age-related macular degeneration (AMD). In cultures of retinal pigment epithelial cells, we have demonstrated that T-cell-derived cytokines induced the upregulation of complement, chemokines and other proteins implicated in AMD pathogenesis. The purpose of this study was to test whether increased plasma levels of cytokines were present in patients with AMD. METHODS: We conducted a case-control study. Age-related macular degeneration status was assessed using standardized multimodal imaging techniques. Plasma was isolated from freshly drawn peripheral venous blood samples and analysed for interleukin (IL)15, IL18, interferon (IFN)γ, soluble tumour necrosis factor (TNF) receptor II (sTNFRII) and complement factor H (CFH) Y402H genotype. RESULTS: We included 136 individuals with early or late forms of AMD and 74 controls. Significantly increased levels of sTNFRII were observed in patients with early or exudative AMD (p < 0.01). After adjusting for CFH Y402H genotype, age, sex and smoking history, the level of sTNFRII remained a significant predictor for prevalence of AMD with odds ratios at 3.0 in the middle and 3.6 in the highest tertiles. Levels of IL15, IL18 and IFNγ were low and not associated with AMD. CONCLUSIONS: Increased plasma level of sTNFRII is found to be associated with AMD. The data supports the observations of low-grade, systemic inflammatory alterations in patients with AMD. However, it remains to be determined whether increased levels of TNFα can be found, which directly reflects an increased activity of macrophages and T cells.