Relación de la presencia de polimorfismos de CFH, HTRA1, ARMS2,VEGF-A y VEGF-R con la aparición de los subtipos de degeneración macular asociada a la edad / The presence of CFH, HTRA1, ARMS2, VEGF-A and VEGF-R and the appearance of age-related macular degeneration sub-types

OBJETIVO: Demostrar la influencia genética en el desarrollo de los distintos tipos de degeneración macular asociada a la edad (DMAE) analizando las distribuciones genotípicas de polimorfismos de CFH,ARMS2, HTRA1, VEGF-A y VEGF-R en pacientes con DMAE exudativa y DMAE atrófica. MÉTODO: Se toman 101 pacientes diagnosticados de DMAE (74 exudativa y 27 atrófica) según las normas del sistema internacional de clasificación Wisconsin. Analizamos los polimorfismos rs1410996 del genCFH, rs10940923 de ARMA2, rs833061 y rs699947 de VEGF-A y rs2071559 de VEGF-R mediante PCR a tiempo real con sondas Taqman y el HTRA1 rs112000638 mediante digestión con endonucleasas de restricción. Analizamos la distribución genotípica de los distintos polimorfismos en nuestro grupo de pacientes con DMAE exudativa y los que presentan DMAE atrófica y comparamos los resultados para cada uno de los genes a estudio. RESULTADOS: No encontramos diferencias estadísticamente significativas (p > 0,05) en la distribución genotípica de los distintos polimorfismos entre pacientes con DMAE atrófica y pacientes con DMAE exudativa en nuestra población, si bien los genotipos considerados «de riesgo» por otros estudios tienden a aparecer de forma más frecuente en la DMAE exudativa, a pesar de no obtener diferencias significativas. CONCLUSIONES: Las variantes alélicas de los genes CFH, ARMS2, HTRA1, VEGF-A o VEGF-R no se asocian con los diferentes subtipos de DMAE, lo que indica que, aunque parece que están implicados en la susceptibilidad a padecer la enfermedad, no están implicados en el desarrollo de las variantes clínicas en nuestra población. Son necesarios nuevos estudios en diferentes poblaciones y con un mayor tamaño muestral para confirmar estos resultados

OBJECTIVE: To demonstrate the genetic influence in the onset of the different age-related macular disease (AMD) subtypes by analysing the genotype distribution of CFH, ARMS2, HTRA1, VEGF-A and VEGF-Rpolymorphisms in patients with neovascular and atrophic AMD. MATERIALS AND METHODS: The study was conducted on 101 consecutive patients with AMD diagnosis (74 exudative, 27 atrophic) following Wisconsin international classification criteria. The CFH rs1410996, ARMS2 rs10940923,VEGF-A rs833061, rs699947, and VEGF-R rs2071559 polymorphisms were analysed using real time PCR with taqman probes, and HTRA1 rs112000638 using restriction endonucleases digestion. A study was made of the genotype distribution of the different polymorphisms in our group of patients with neovascular AMD and those with the atrophic type, and a comparison was made of the results for each one of the genes studied. RESULTS: No statistically significant differences (P>.05) were found in the genotype distribution of the different polymorphisms between patients with neovascular AMD and patients with atrophic AMD in our population, although the 'risk' genotypes tended to appear more frequently in patients with neovascular AMD, despite the lack of statistical significance. CONCLUSIONS: Allelic variants of CFH, ARMS2, HTRA1, VEGF-A or VEGF-R genes are not associated with the different AMD subtypes. This suggests that, although the polymorphisms seem to be associated with the disease susceptibility, they are not involved in the onset of the different clinical variants of AMD. Further studies in different populations, and with a larger cohort of patients, are needed to confirm these results

The presence of CFH, HTRA1, ARMS2, VEGF-A and VEGF-R and the appearance of age-related macular degeneration sub-types.

OBJECTIVE: To demonstrate the genetic influence in the onset of the different age-related macular disease (AMD) subtypes by analysing the genotype distribution of CFH, ARMS2, HTRA1, VEGF-A and VEGF-R polymorphisms in patients with neovascular and atrophic AMD. MATERIALS AND METHODS: The study was conducted on 101 consecutive patients with AMD diagnosis (74 exudative, 27 atrophic) following Wisconsin international classification criteria. The CFH rs1410996, ARMS2 rs10940923, VEGF-A rs833061, rs699947, and VEGF-R rs2071559 polymorphisms were analysed using real time PCR with taqman probes, and HTRA1 rs112000638 using restriction endonucleases digestion. A study was made of the genotype distribution of the different polymorphisms in our group of patients with neovascular AMD and those with the atrophic type, and a comparison was made of the results for each one of the genes studied. RESULTS: No statistically significant differences (P>.05) were found in the genotype distribution of the different polymorphisms between patients with neovascular AMD and patients with atrophic AMD in our population, although the "risk" genotypes tended to appear more frequently in patients with neovascular AMD, despite the lack of statistical significance. CONCLUSIONS: Allelic variants of CFH, ARMS2, HTRA1, VEGF-A or VEGF-R genes are not associated with the different AMD subtypes. This suggests that, although the polymorphisms seem to be associated with the disease susceptibility, they are not involved in the onset of the different clinical variants of AMD. Further studies in different populations, and with a larger cohort of patients, are needed to confirm these results.

Síndrome de pseudo-duane paraneoplásico secundario a tumor de mama / Pseudo-duane's paraneoplasic syndrome secondary to breast tumor

Se describe el caso clínico de una mujer de 50 años con antecedentes personales de cáncer de mama, que refiere alteraciones de los movimientos oculares. En la exploración se observa una limitación de la abducción y estrechamiento de la hendidura palpebral en aducción en ambos ojos. RMN craneal y orbitaria normales. Marcadores tumorales con títulos bajos. Se realiza el diagnóstico de Síndrome de pseudo- Duane, ya que se trata de un síndrome restricitivo adquirido. En este caso, su presentación clínica es similar al síndrome Duane tipo I, siendo contradictorio a lo descrito en publicaciones previas. Por otra parte, este síndrome está relacionado en el tiempo con su patología oncológica y la RMN es normal, por lo que lo consideramos un síndrome paraneoplásico. Destacamos la originalidad del caso debido a su inusual etiología, y clínica (AU)

We report the case of a 50 years-old woman with history of breast tumor and anormal ocular motility. An examination of ocular motility revealed limited abduction and narrowing of the palpebral fissure on adduction. Orbital and cranial nuclear magnetic resonance were normal. Tumor markers had low levels. We think about her oncologic history because of the beginning of the sintomatology in this period of time. The diagnosis was Pseudo-Duane syndrome, wich is a restrictive acquired syndrome. Despite clinical presentation was similar to Duane I syndrome, it is enterely different from it. We highlight the originality of the case due to its inusual ethiology(only one case published previously) and its clinical presentation (AU)

Perforación corneal como primera manifestación de síndorme de Sjören secundario a artritis reumatoide / Corneal melts as the initial manifestation of sjögren syndrome secondary to rheumatoid arthritis

La artritis reumatoide es una enfermedad sistémica inflamatoria crónica frecuente, de etiología desconocida. El síndrome de Sjögren puede ir asociado a dicha patología. El curso clínico de la artritis reumatoide a nivel ocular es muy variable y el diagnóstico temprano es determinante para prevenir graves complicaciones. Presentamos el caso de una mujer de 64 años de edad que acudió al Servicio de Urgencias por presentar ojo rojo bilateral con fotofobia, lagrimeo continuo, dolor y disminución de la agudeza visual. En la exploración se objetivó importante adelgazamiento del estroma corneal en OD y perforación corneal OI, que requirió recubrimiento tectónico con membrana amniótica. Los análisis serológicos mostraron los siguientes resultados: Factor Reumatoide+, ANA+, ENA Anti-Ro/SSA+, ENA Anti-La/SSB+. La paciente fue diagnosticada de Artritis Reumatoide y Síndrome de Sjögren secundario. Desde entonces, sigue un tratamiento sistémico con corticoides y azatioprina. Aproximadamente, el 25% de los pacientes desarrollan enfermedad oftalmológica, esencialmente queratoconjuntivitis seca (25%), epiescleritis, escleritis y queratitis. Estas manifestaciones son en general poco severas, pero hay un pequeño porcentaje de pacientes, como el caso que aquí presentamos, que sufren una inflamación ocular grave y que sin tratamiento inmunosupresor precozmente instaurado, pueden desarrollar úlceras corneales estériles, centrales o periféricas, que les puede llevar incluso a la perforación y destrucción del globo (AU)

Rheumatoid arthritis(RA) is a common chronic inflammatory autoinmune disease, with unknown etiology. Approximately 11-31% of RA patients have secondary Sjögren´s syndrome. Ophthalmologic manifestations of these diseases can cause corneal scarring, ulceration, infection, and even perforation; thus, although the prognosis is good for most patients with Sjögren syndrome and ophthalmologic features, individuals with complications have much guarded prognosis. We report the case of a 65 years old woman with photophobia, pain, tearing and blurred vision in both eyes. Slit lamp exam showed an important corneal melting right eye, and corneal perforation left eye, which required amniotic membrane transplantation. The diagnosis was: Rheumatoid Arthritis and secondary Sjögren´s Syndrome. Azathioprine treatment was started in combination with oral steroids. Approximately 25% of patients have ocular involvement, and keratoconjunctivitis sicca is the most frequent ocular complication. Although the prognosis is good in most cases, an early diagnosis is necessary to avoid several complications (AU)

Cambios morfométricos de las células del endotelio corneal en el síndrome pseudoexfoliativo y glaucoma pseudoexfoliativo / Morphometric changes of corneal endothelial cells in pseudoexfoliation syndrome and pseudoexfoliation glaucoma

Objetivo: Analizar el patrón morfométrico de las células endoteliales de la córnea y el espesor corneal central (ECC) en los ojos con pseudoexfoliativo (PEX) con y sin glaucoma, y compararlos con ojos normales y con glaucoma primario de ángulo abierto (GPAA). Método: Se incluyeron 166 pacientes en el estudio: 36 sujetos con síndrome seudoexfoliativo, 30 con glaucoma seudoexfoliativo (GPEX), 40 con GPAA y 60 pacientes normales. Los parámetros evaluados con el microscopio especular de no contacto fueron la densidad de células endoteliales (DCE), el coeficiente de variación ( CV ) del tamaño celular y el porcentaje de hexagonalidad. El ECC se midió con paquimetría de contacto. Resultados: La DCE y el porcentaje de hexagonalidad celular fueron menores en los sujetos con PEX y GPAA respecto al grupo control, mientras que el CV del tamaño celular fue mayor. Considerando los 2 grupos de ojos con PEX, se observó una tendencia hacia una mayor pérdida de células endoteliales y de modificaciones en los parámetros morfométricos en los ojos con GPEX. Las alteraciones en el patrón especular aumentaron progresivamente con la edad. No hubo diferencias significativas en el valor medio de ECC entre los 4 grupos. Conclusión: La densidad de células endoteliales está significativamente disminuida y el pleomorfismo y polimegatismo celular incrementado en los ojos con PEX, especialmente cuando la presión intraocular es alta (AU)

Objetive: To evaluate the corneal endothelial morphometry and central corneal thickness (CCT) in pseudoexfoliative (PEX) eyes with and without glaucoma and to compare with normal eyes and eyes with primary open-angle glaucoma (POAG).Method: A total of 166 patients were included in this study: 36 eyes with pseudoexfoliation syndrome (PXS), 30 eyes with pseudoexfoliation glaucoma (PXG), 40 eyes with POAG, and 60normal eyes. Corneal endothelial cell density (ECD), coefficient of variation (CV) in cell size, and percentage of hexagonal cells, were measured using a non-contact specular microscope, whereas CCT was measured with an ultrasonic pachymeter. Results: ECD and percentage of hexagonal cells were lower in PEX groups and in the POAG group compared with normal eyes, while the CV in cell size was greater. There was a tendency for greater cell loss and morphological abnormalities of the corneal endothelial cells in PXG eyes compared to PXS eyes, when all pseudoexfoliative eyes were analyzed together. Changes in endothelial cells increased with age. There were no significant differences in mean CCT between the four groups. Conclusion: Endothelial cell density is significantly decreased, and pleomorphism and polymegathism of cells are increased in PEX eyes, particularly when intraocular pressure is high (AU)

[Morphometric changes of corneal endothelial cells in pseudoexfoliation syndrome and pseudoexfoliation glaucoma]. / Cambios morfométricos de las células del endotelio corneal en el síndrome pseudoexfoliativo y glaucoma pseudoexfoliativo.

OBJECTIVE: To evaluate the corneal endothelial morphometry and central corneal thickness (CCT) in pseudoexfoliative (PEX) eyes with and without glaucoma and to compare with normal eyes and eyes with primary open-angle glaucoma (POAG). METHOD: A total of 166 patients were included in this study: 36 eyes with pseudoexfoliation syndrome (PXS), 30 eyes with pseudoexfoliation glaucoma (PXG), 40 eyes with POAG, and 60 normal eyes. Corneal endothelial cell density (ECD), coefficient of variation (CV) in cell size, and percentage of hexagonal cells, were measured using a non-contact specular microscope, whereas CCT was measured with an ultrasonic pachymeter. RESULTS: ECD and percentage of hexagonal cells were lower in PEX groups and in the POAG group compared with normal eyes, while the CV in cell size was greater. There was a tendency for greater cell loss and morphological abnormalities of the corneal endothelial cells in PXG eyes compared to PXS eyes, when all pseudoexfoliative eyes were analyzed together. Changes in endothelial cells increased with age. There were no significant differences in mean CCT between the four groups. CONCLUSION: Endothelial cell density is significantly decreased, and pleomorphism and polymegathism of cells are increased in PEX eyes, particularly when intraocular pressure is high.

Farmacogénetica y degeneración macular asociada a la edad, hacia un tratamiento individualizado de la enfermedad / Pharmacogenetics and Age-related Macular Degeneration, towards an individualized treatment of the disease

No disponible

VEGF A (rs699947 and rs833061) and VEGFR2 (rs2071559) gene polymorphisms are not associated with AMD susceptibility in a Spanish population.

PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease due to interaction between genetic and environmental factors. Increased angiogenesis plays a central role in AMD development. Previous studies on the potential link between AMD and vascular endothelial growth factor (VEGFA) and vascular endothelial growth factor receptor (VEGFR) have yielded conflicting results. We have analysed if polymorphisms in genes coding for VEGFA and VEGFR are associated to susceptibility to suffer AMD in a cohort of Spanish subjects. PATIENTS AND METHODS: We obtained peripheral blood samples from 151 patients with diagnosis of exudative AMD. We also studied 91 healthy subjects matched by age. We studied VEGFA rs699947 and rs833061, and VEGFR2 rs2071559 polymorphisms using real-time PCR with TaqMan probes. RESULTS: We did not find statistically significant differences in genotypic distribution of VEGF rs699947 and rs833061 polymorphisms between patients and controls. However, analysis of VEGFR2 rs2071559 polymorphism shows that carriers of GG genotype are more frequent in subjects with AMD (p: 0.032; Odds Ratio(OR): 1.933; confidence interval (CI): 1.053-3.549), but, when corrected by Bonferroni testing, the result was found to be not significant. CONCLUSION: Our study shows that VEGFA rs699947 and rs833061 and VEGFR2 rs2071559 polymorphisms do not modify the risk of suffering AMD in a Spanish population.