RESUMEN
PURPOSE: Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. METHODS: Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). RESULTS: All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452-2A>T or IVS36-2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. CONCLUSIONS: We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.
Asunto(s)
Colágeno Tipo I/genética , Glaucoma de Ángulo Abierto/complicaciones , Glaucoma de Ángulo Abierto/genética , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Anciano , Codón sin Sentido , Cadena alfa 1 del Colágeno Tipo I , Proteínas del Citoesqueleto/genética , Análisis Mutacional de ADN , Proteínas del Ojo/genética , Femenino , Estudios de Asociación Genética , Glaucoma de Ángulo Abierto/patología , Glicoproteínas/genética , Humanos , Persona de Mediana Edad , Mutagénesis Insercional , Nervio Óptico/patología , Sitios de Empalme de ARN , Eliminación de Secuencia , Campos VisualesAsunto(s)
Presión del Líquido Cefalorraquídeo/fisiología , Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Ángulo Abierto/cirugía , Presión Intraocular/fisiología , Disco Óptico/patología , Enfermedades del Nervio Óptico/fisiopatología , Antihipertensivos/uso terapéutico , Humanos , TrabeculectomíaRESUMEN
OBJECTIVE: To correlate losses of retinal thickness in the perifoveal area in glaucoma as measured by the Retinal Thickness Analyzer (Talia Technology Ltd, Israel) with optic nerve and visual field changes in glaucoma patients and suspects. METHODS: Observational case series of 55 consecutive patients from the Glaucoma Service who either presented with a diagnosis of glaucoma or were referred for evaluation of suspected glaucoma. The Retinal Thickness Analyzer (Talia Technology, Ltd.) was used to obtain retinal thickness maps. Retinal thickness analysis, visual field testing, and stereophotography of the optic nerve head were performed, and a glaucoma specialist who was masked to patient status and identity data randomly graded the level of severity of each parameter. Spearman rank correlations were used to assess the relationships among the three numerical measures. RESULTS: Retinal thickness losses correlated more strongly with severity of optic nerve head cupping (r = 0.75), whereas both of these measures correlated less strongly with the severity of visual field loss (r = 0.54). CONCLUSIONS: Retinal thickness measurements at the posterior pole provide another measure of neural loss in glaucoma, and may help in the clinical assessment of optic nerve cupping. However, there are limitations of the technology that must be considered.