RESUMO
A study on the role of CFH, HTRA and IL-8 gene polymorphism in age-related macular degeneration (AMD) development has been conducted. At the first stage of the study genetic testing was done in 69 patients with exudative AMD and 370 random Moscow citizens without the disease. The goal of the second stage was to determine the influence of gene polymorphism on patient's response to endovitreal ranibizumab treatment. For that, visual acuity and foveal thickness were assessed before and after ranibizumab injections in 120 patients with wet AMD. All patients were genotyped for the genes of interest. The results showed that the presence of homozygous 402H polymorphism in CFH gene, as well as homozygous (-625)A mutation in HTRA1 gene, determines certain clinical presentations. Moreover, visual acuity below 0.1 and presence of 402H, (-625)A and (-251)A alleles in both copies of all three genes (CFH, HTRA and IL-8) are negative predictors of disease severity and antiangiogenic treatment response.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Fator H do Complemento/uso terapêutico , Interleucina-8/uso terapêutico , Degeneração Macular/genética , Farmacogenética/métodos , Polimorfismo Genético , Serina Endopeptidases/uso terapêutico , Alelos , Fator H do Complemento/genética , Inativadores do Complemento/uso terapêutico , DNA/genética , Feminino , Angiofluoresceinografia , Fundo de Olho , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Homozigoto , Humanos , Interleucina-8/genética , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Masculino , Ranibizumab , Serina Endopeptidases/genética , Acuidade VisualRESUMO
In recent decades the problem of low vision and blindness in elderly people became major and socially significant issue. The number of patients having age-related macular degeneration (AMD) in association with glaucoma grows all over the world that attaches medical and social value to this problem. 102 patients with AMD were under follow-up, 7 of them had primary open-angle glaucoma (POAG). Three consecutive injections of ranibizumab resulted in visual acuity increase from 0.21 +/- 0.17 till 0.37 +/- 0.12. The mean retinal thickness in foveal zone decreased from 289.36 +/- 88.73 till 230.47 +/- 88.02 microm. Ocular hypertension within 12 hours after procedure was observed in 13 (12.7%) of 102 patients. In all cases intraocular pressure (IOP) returned to preoperative values in 3 days after hypotensive medical treatment. In one case trabeculectomy was performed simultaneously with ranibizumab intravitreal injection, the next two injections were performed in a month intervals. So the problem of IOP increase after intravitreal injections remains unsolved. Glaucoma is not an absolute contraindication to intravitreal injections in treatment of exudative AMD although patients with associated conditions need individual approach in terms of both IOP compensation and number of ranibizumab injections.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Glaucoma/complicações , Pressão Intraocular/fisiologia , Degeneração Macular/fisiopatologia , Monitorização Fisiológica/métodos , Tonometria Ocular/métodos , Idoso , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/etiologia , Masculino , Ranibizumab , Retina/patologiaRESUMO
A detailed analysis of influence of HTRA (serine peptidase) and VEGF (vascular endothelial growth factor) genes mutations is presented. The presence of one gene copy with allele of A- polymorphism rs1120638 of HTRA1 gen, T- polymorphism rs10490924 and de11443in54 of ARMS2 gene increases the risk of CNV in patients with AMD. The feature of clinical presentation in patients with CNV associated with (-625) A mutation of promoter region of HTRA1 gene in two chromosomes was fulminant course of the disease from exudative to scarring processes with fibrous tissue formation not just with sub-, but also intra- and preretinal localization. Genetic screening showed that combination of studied mutations (402H, (-625) A and (-251) A in both gene copies of CFH, HTRA and IL-8) results in the most severe and rapidly progressing form of the disease. Two new mutations were revealed in promoter region of VEGF gene: G > A replacement in position of (-72) nucleotide from transcription start and G > A replacement in 5'-nontranslated region of the 1st gene exon in position of (+31) nucleotide from transcription start.
Assuntos
Neovascularização de Coroide , Degeneração Macular/genética , Mutação , Miopia Degenerativa/genética , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genética , Fator A de Crescimento do Endotélio Vascular/genética , Corioide/irrigação sanguínea , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Neovascularização de Coroide/fisiopatologia , Fator H do Complemento/genética , Feminino , Angiofluoresceinografia , Predisposição Genética para Doença , Humanos , Interleucina-8/genética , Degeneração Macular/complicações , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/complicações , Neovascularização Patológica/genética , Vasos Retinianos/patologia , Acuidade VisualRESUMO
Genetic analysis was performed in patients with subretinal neovascularization (CNV). The results showed significant association of CFH (compliment factor H) gene polymorphism with increase (rs1061170, rs514943 and rs380390) or decrease (rs529825, rs7524776, rs1831281, rs2274700, rs1576340, rs12144939, rs7540032) of CNV development risk. The incidence of IL-8 gene mutation was significantly (p = 0.008) higher in patients after chorioretinitis. Apparently -125 > A polymorphism in patients with chorioretinitis increases risk of CNV development, thus promoting raise of proangiogenic factors concentration in eyes with inflammatory background. The clinical presentation in patients with AMD and myopic disease associated with (-125) A mutation of promoter region of IL-8 gene was similar to that of patients with chorioretinitis. The features are the following: focal pattern, no drusen and RPE detachment, predominantly classic form of CNV (without occult pattern), formation of well-organized newly developed vessels.