Nuestros investigadores

Manuel Sáenz de Viteri Vázquez

Departamento
Oftalmología
Clínica Universidad de Navarra. Clínica Universidad de Navarra
Líneas de investigación
Degeneración Macular Asociada a la Edad, Fármacos antiangiogénicos, Retinopatía diabética, Farmacología y toxicidad retiniana

Publicaciones científicas más recientes (desde 2010)

Autores: Saenz-de-Viteri, Manuel; Cudrnak, T.;
Revista: LEUKEMIA AND LYMPHOMA
ISSN 1029-2403  Vol. 60  Nº 3  2019  págs. 842 - 844
Autores: Saenz-de-Viteri, Manuel, (Autor de correspondencia); et al.
Revista: APPLIED SCIENCES
ISSN 2076-3417  Vol. 8  Nº 12  2018  págs. 2441
Optical coherence tomography angiography (OCT-A) is a novel, rapidly evolving, non-invasive imaging technique that allows images of the retinal vasculature to be obtained in a few seconds. Blood vessels of different retinal vascular plexuses and the foveal avascular zone (FAZ) can be examined without the administration of any contrast or dye. Due to these characteristics, OCT-A could be an excellent complementary test to study retinal vascularization in children. Until now, most of the studies with OCT-A have been conducted in adults and only a few have been carried out in children. In this review, we describe the principles and advantages of OCT-A over traditional imaging methods and provide a summary of the OCT-A findings in retinopathy of prematurity and other retinal and optic disc pathologies in children. In view of the promising results from studies, the advantages of a relatively rapid and non-invasive method to assess the retinal vasculature makes OCT-A a tool of which applications in the field of pediatric ophthalmology will be expanded in the near future for patient diagnosis and follow-up in every day clinical practice.
Autores: Fernandez-Robredo, P, (Autor de correspondencia); Recalde, Sergio; Hernández, María; et al.
Revista: FRONTIERS IN IMMUNOLOGY
ISSN 1664-3224  Vol. 9  2018  págs. 1862
Purpose: To explore the relationship between plasma C-reactive protein (CRP) levels, the main ARMS2 gene single nucleotide polymorphism (SNP), and gender in patients with neovascular age-related macular degeneration (wet AMD). Methods: Our study included 131 patients with wetAMD [age-related eye disease study (AREDS) category 4] and 153 control participants (AREDS category 1) from two Spanish retinal units. CRP levels were determined on blood samples by high-sensitivity ELISA assay. According to their CRP level, subjects were categorized into three well-established CRP categories: low (< 1.00 mg/L, L-CRP), moderate (1-2.99 mg/L, M-CRP), and high (> 3.00 mg/L, H-CRP). Genomic DNA was extracted from oral swabs using QIAcube (Qiagen, Hilden, Germany) and the A69S; rs10490924 of ARMS2 gene was genotyped by allelic discrimination with validated TaqMan assays (Applied Biosystems, Foster City, CA, USA). Univariate and multivariate logistic regression adjusted for age was used to analyze the genomic frequencies and to calculate odds ratio (OR) using SNPStats software. Results: Considering CRP risk categories, H-CRP group showed a significant [OR 4.0 (1.9-8.3)] association with wetAMD compared to L-CRP group. The risk genotypes of A69S (TT) SNPs showed an association with wetAMD risk [OR 14.0 (4.8-40.8)]. Interestingly, the gender stratification of the CRP categories showed a significant increase in CRP levels in wetAMD women compared with control women [OR 6.9 (2.2-22.3)] and with wetAMD men [OR 4.6 (1.3-16.9)]. In addition, the subgroup analysis of CRP within A69S genotype and gender showed a link in women between the A69S and CRP levels in the AMD group compared to controls [OR 4.2 (1.4-12.6)]. Conclusion: Our study shows, for the first time, that a different genetic association related with gender could contribute to AMD risk. As a consequence, the risk of female gender in the different CRP levels and A69S SNP frequencies could be taken into consideration to the established risk relationship of high levels of CRP and its association with risk A69S genotype.
Autores: González Salinas, R., (Autor de correspondencia); Garza Leon, M.; Saenz-de-Viteri, Manuel; et al.
Revista: INTERNATIONAL OPHTHALMOLOGY
ISSN 0165-5701  Vol. 38  Nº 5  2017  págs. 1907 - 1913
PURPOSE: To compare the cumulative dissipated energy (CDE), aspiration time and estimated aspiration fluid utilized during phacoemulsification cataract surgery using two phacoemulsification systems . METHODS: A total of 164 consecutive eyes of 164 patients undergoing cataract surgery, 82 in the active-fluidics group and 82 in the gravity-fluidics group were enrolled in this study. Cataracts graded NII to NIII using LOCS II were included. Each subject was randomly assigned to one of the two platforms with a specific configuration: the active-fluidics Centurion ® phacoemulsification system or the gravity-fluidics Infiniti ® Vision System. CDE, aspiration time (AT) and the mean estimated aspiration fluid (EAF) were registered and compared. RESULTS: A mean age of 68.3 ± 9.8 years was found (range 57-92 years), and no significant difference was evident between both groups. A positive correlation between the CDE values obtained by both platforms was verified (r = 0.271, R 2 = 0.073, P = 0.013). Similarly, a significant correlation was evidenced for the EAF (r = 0.334, R 2 = 0.112, P = 0.046) and AT values (r = 0.156, R 2 = 0.024, P = 0.161). A statistically significantly lower CDE count, aspiration time and estimated fluid were obtained using the active-fluidics configuration when compared to the gravity-fluidics configuration by 19.29, 12.10 and 9.29%, respectively (P = 0.001, P < 0.0001 and P = 0.001). CONCLUSIONS: The active-fluidics Centurion ® phacoemulsification system achieved higher surgical efficiency than the gravity-fluidics Infiniti ® IP system for NII and NIII cataracts.
Autores: Fernandez-Robredo, P; Hernández, María; Recalde, Sergio; et al.
Revista: INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404  Vol. 58  Nº 8  2017 
Autores: Saenz-de-Viteri, Manuel; Fernandez-Robredo, P; Hernández, María; et al.
Revista: BIOCHEMICAL PHARMACOLOGY
ISSN 0006-2952  Vol. 103  2016  págs. 129 - 139
We assessed the effect of single and repeated doses of bevacizumab, ranibizumab, and aflibercept on cell viability, proliferation, permeability, and apoptosis of ARPE-19 cells. MTT and BrdU assays were used to determine viability and proliferation after single or repeated doses of anti-VEGF drugs under normal and oxidative stress conditions. Caspase-3 expression after single and repeated doses of the 3 drugs was assessed using immunofluorescence. Transepithelial-electrical-resistance (TER) was measured to study the effect of anti-VEGFs on retinal pigment epithelium (RPE) permeability under normal and oxidative stress conditions. Flow cytometry was used to detect intracellular accumulation of the drugs. Finally, a wound healing assay was performed to investigate the effect of the drugs on RPE cell migration. Single and multiple doses of anti-VEGF drugs had no effect on cell viability and proliferation. The oxidative effect of H2O2 decreased cell viability and proliferation; however, no difference was observed between anti-VEGF treatments. Immunofluorescence performed after single and repeated doses of the drugs revealed some caspase-3 expression. Interestingly, anti-VEGFs restored the increased permeability induced by H2O2. The 3 drugs accumulated inside the cells and were detectable 5 days after treatment. Finally, none of the drugs affected migration. In conclusion, no measureable toxic effect was observed after single or repeated doses of VEGF antagonists under normal and oxidative stress. Intracellular accumulation of the drugs does not seem to be toxic or affect cell functions. Our study suggests that anti-VEGFs could have a preventive effect on the maintenance of the RPE barrier under oxidative stress.
Autores: Saenz-de-Viteri, Manuel, (Autor de correspondencia); Sádaba, Luis Manuel;
Revista: MEDICINE (BALTIMORE)
ISSN 0025-7974  Vol. 95  Nº 6  2016  págs. e2680
Low serum levels of vitamin A confirmed the diagnosis and patient started vitamin A supplementation. Visual fields, macular thickness, and ganglion cell layer thickness were recorded and monitored 1 month, 6 months, and 1 year after the beginning of therapy. Visual fields were significantly altered and central macular thickness and ganglion cell layer thickness were reduced, but the first 2 showed a significant recovery with vitamin supplementation therapy. By the 1st month of treatment patient referred a complete remission of visual symptoms. Further, we observed hyperreflective material accumulating beneath a partially disrupted ellipsoid band in the high definition optical coherence tomography that also improved progressively with vitamin repletion.Newer and more sophisticated imaging systems have increased our knowledge of the mechanisms responsible for retinal diseases. To our knowledge, this is the first description of the effect of vitamin A deficiency and vitamin supplementation on macular thickness. This case also highlights the importance of considering bariatric bypass surgery as a cause of vitamin A deficiency in developed countries.
Autores: Gonzalez-Salinas R; Guarnieri, A; et al.
Revista: PATIENT PREFERENCE AND ADHERENCE
ISSN 1177-889X  Vol. 10  2016  págs. 1795-1801
Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) like ketorolac, which inhibit the synthesis of prostaglandins, are used to decrease intraoperative miosis, control pain and inflammation associated with cataract surgery, and to prevent the development of cystoid macular edema following surgery. Recently, a new combination of phenylephrine and ketorolac (Omidria®) has been approved by United States Food and Drug Administration for use during cataract surgery to maintain intraoperative mydriasis, prevent miosis, and reduce postoperative pain and inflammation. Clinical trials have shown that this new combination is effective, combining the positive effects of both drugs with a good safety profile and patient tolerability. Moreover, recent reports suggest that this combination is also effective in patients with high risk of poor pupil dilation. In conclusion, cataract is a global problem that significantly affects patients' quality of life. However, they can be managed with a safe and minimally invasive surgery. Advances in surgical techniques and newer pharmacological agents such as the combination of phenylephrine and ketorolac, together with better intraocular lenses, have greatly improved visual outcomes and thus patients' expectations regarding visual recovery are also increasing.
Autores: Fernandez-Robredo, P; Saenz-de-Viteri, Manuel; Recalde, Sergio; et al.
Revista: INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404  Vol. 57  Nº 12  2016  págs. 3363
Purpose : To evaluate intracellular accumulation and the effect of bevacizumab, ranibizumab and aflibercept on cellular migration and permeability in a human retinal pigmented epithelium (RPE) cell line. Methods : Experiments were performed on ARPE-19 cells and anti-VEGF drugs were diluted to a concentration equivalent to their clinical doses. Anti-VEGFs were labeled with Alexa 488 fluorochrome to detect intracellular accumulation by flow cytometry at 1 hour, 1 day and five days. Further, transepithelial electrical resistance (TEER) was measured in transwells at 2, 4, 6, 12 and 24 hours to assess the effect of anti-VEGFs on RPE permeability. Moreover, TEER was also measured at the same time points in the presence of different doses of H2O2 to replicate the oxidative environment observed in Age-related Macular Degeneration (AMD). Wound healing was assessed to determine the effect of the drugs on cellular migration during 72 hours to measured cell covered area by ImageJ software. Results : The three studied drugs were observed to accumulate inside the cells and they were still detectable five days after being added (p<0.001). A dose-dependent increased in cell permeability was observed in cells treated with H2O2 (p<0.05) that was reverted from the time point of 12 hours and became non-significant. Anti-VEGF drugs did not affect the permeability along time and they were able to reduce the effect of H2O2. Cells treated with anti-VEGF drugs at the beginning of the experiment showed a significant decrease in the damage produced by H2O2 at 4, 6 and 12 hours (p<0.05) with no significant difference between the treatments. On the contrary, when anti-VEGF treatment was used 6 hours after the beginning of the experiment, none of the 3 drugs decreased the deleterious effect of H2O2 in TEER. Anti-VEGF drugs did not affect cellular migration. Conclusions : Intracellular accumulation of bevacizumab, ranibizumab and aflibercept does not seem to be toxic or affect cell permeability and migration. Moreover, our study suggests that anti-VEGFs have a positive effect on the barrier function of the RPE.
Autores: Moreno, Javier; Alfonso, Belén; Saenz-de-Viteri, Manuel;
Revista: ANNALS D`OFTALMOLOGIA
ISSN 1133-7737  Vol. 23  Nº 4  2015  págs. 32
Autores: Velázquez Villoria, Alvaro; Saenz-de-Viteri, Manuel; et al.
Revista: ARCHIVOS DE LA SOCIEDAD CANARIA DE OFTALMOLOGIA
ISSN 0211-2698  Vol. 26  2015  págs. 55 - 67
Objetivo: Evaluar la relación entre el tamaño del disco óptico y la medición de la Capa de Fibras Nerviosas de la Retina (CFNR) realizada por Cirrus OCT. Investigar su influencia en la capacidad diagnóstica. Diseño: Observacional, estudio transversal. Metodo: Se incluyeron 588 ojos (290 controles y 298 glaucomatosos). El tamaño del disco se determinó midiendo el diámetro vertical , horizontal y su área. En el grupo control, se evaluó la asociación entre la CFNR y el tamaño del disco mediante regresión lineal. El total de la muestra se dividió en cuartiles (área ¿1,56 mm2; 1.57-1.78 mm2; 1,79-2,08 mm2; ¿ 2,09 mm2), y se calcularon áreas bajo las curvas (AUC) ROC para cada grupo. Mediante el test de la t de Student para datos independientes se comparó el tamaño del disco entre ojos con diagnóstico incorrecto (falsos positivos ¿FP¿ y falsos negativos ¿FN¿) y correcto (verdaderos positivos -VP- y verdaderos negativos -VN-) Resultados: Para la medición de la CFNR media (Average), únicamente se encontró una correlación estadísticamente significativa (r=0,16, p=0,02) con el diámetro vertical. Sin embargo, para la medición en el cuadrante inferior, esta asociación también se vio con el área (r=0,13, p=0,03). Las mejores AUC se obtuvieron para el grupo 2 (áreas entre 1,57 -1,78 mm2) , (AUC: 0,89, IC95%: 0,82 a 0,93, p< 0,001, y AUC: 0,90, IC95%: 0,83 a 0,95, p< 0,001, Average e inferior, respectivamente). En los FN, los tamaños de disco fueron mayores que en los VN. Estas diferenci
Autores: Reiter, N.; Saenz-de-Viteri, Manuel; Recalde, Sergio; et al.
Revista: INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404  Vol. 56  Nº 7  2015  págs. 2016
Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Controversy exists regarding the safety of agents that inhibit vascular endothelial growth factor (VEGF). In this study we performed different assays to compare in vitro cytotoxicity of bevacizumab (B), ranibizumab (R), and aflibercept (A) at clinical doses on retinal pigment epithelia (RPE) cell line (ARPE19). Methods: Cellular toxicity was assessed through MTT cell viability and BrdU proliferation assays after single or repeated doses of the anti-VEGF drugs. Immunofluorescence (IF) for zonula ocludens (ZO-1) was performed. Intracellular accumulation was determined by IF (antihuman Cy3) one and five days after treatment with B, R and A. IF was also used to determine the activity of caspase-3 after single or repeated doses of B, R and A. The effect of anti-VEGF agents on cell phagocytosis of fluorescent latex beads was also assessed. Finally, RPE permeability 24, 48 and 72 hours after anti-VEGF treatments was studied using a FITC permeability assay on transwell inserts. Statistical analysis was performed (SPSS 20). Results: There were no statistically significant differences in cell viability or cell proliferation after single or repeated doses of B, R and A. The tight junction labeled with ZO-1 was not altered with treatments. On the contrary, intracellular accumulation of R was significantly lower compared to the other anti-VEGF agents up to 5 days after initial treatment. Phagocytosis was significantly lower in cells treated with R and A (34% and 28.8%, p<0.001) compared to the control group, but not statistically significant in cells treated with B (75%, p=0.104). We found no significant differences in caspase-3 activity between the 3 drugs neither 24 hours nor one week after treatment. The anti-VEGF agents did not affect FITC permeability when compared to the control group at any time points. Conclusions: Our results suggest that ranibizumab is the anti-VEGF agent that accumulates intracellularly to a lesser extent. However this finding does not affect in vitro cell viability and proliferation in the short time. Furthermore, we did not find a significant effect in cell death, cellular permeability or phagocytosis after single or repeated doses of the treatments. These results imply that anti-VEGF agents at clinical doses are safe in ARPE19 cells.
Autores: Saenz-de-Viteri, Manuel; Fernandez-Robredo, P; et al.
Revista: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
ISSN 1942-0900  Vol. 2014  Nº 637137  2014 
Photochemical damage occurs after an exposure to high energy radiation within the visible spectrum of light, causing morphological changes in the retina and the formation of superoxide anion. In this study we created a model of phototoxicity in rabbits. Animals were exposed to a light source for 120 minutes and were sacrificed immediately or one week after exposure. Outer nuclear layer and neurosensory retina thickness measurements and photoreceptor counting were performed. Caspase-1 and caspase-3 were assessed by immunohistochemistry. Dihydroethidium was used to evaluate in situ generation of superoxide and thiobarbituric acid reactive substances were measured in retinal homogenates as indicators of lipid peroxidation. The total antioxidant capacity and oxidative ratio were also determined. Retinas from rabbits exposed to light showed higher levels of lipid peroxidation than the unexposed animals and a decrease in outer nuclear layer and neurosensory retina thickness. Our study demonstrates that light damage produces an increase in retinal oxidative stress immediately after light exposure that decreases one week after exposure. However, some morphological alterations appear days after light exposure including apoptotic phenomena. This model may be useful in the future to study the protective effect of antioxidant substances or new intraocular lenses with yellow filters.
Autores: Saenz-de-Viteri, Manuel; Fernandez-Robredo, P; et al.
Revista: INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
ISSN 1672-5123  Vol. 6  Nº 6  2013  págs. 801-804
Two controlled, prospective, randomized, single-blind studies were performed. In the first study, a total of 80 eyes from 40 outpatient-clinic patients were analyzed. PT drops were applied to the right eye, and a MY device was inserted in the left eye for 30min. Time until maximal pupil dilation for each eye was then assessed. In the second study, 80 eyes from 80 patients undergoing cataract surgery were analyzed. Pupil dilation was achieved using either PT drops three-times for one hour prior to surgery (40 patients), or a MY device was inserted one hour prior to surgery (40 patients). In the first study, MY achieved superior mydriasis compared to PT eye drops at 90min (9.04±1.33mm vs 8.78±1.37mm, P=0.012). However MY took longer than PT drops to achieve maximal dilation, and mydriasis was inferior in eyes with MY compared to PT drops at 30min (7.21±1.73mm vs 8.22±1.43mm, P<0.001), the two groups only becoming similar by 60min (8.85±1.44mm vs 8.71±1.27mm, P=0.236). In the second study, both MY and PT achieved similar levels of mydriasis at the beginning of surgery (8.75±0.76mm with MY vs 8.77±0.63mm with PT), and also at the end of surgery (7.96±1.06mm with MY vs 8.32±0.72mm with PT), with no significant difference between groups (P=0.08). MY was well tolerated and cardiovascular effects were not influenced by dilation method.
Autores: Saenz-de-Viteri, Manuel; Jimenez, M.; Bautista de Ludo, V.;
Revista: CLINICAL IMMUNOLOGY
ISSN 1521-6616  Vol. 135  Nº Supl.  2010  págs. S77 - S78
Autores: García, Alfredo; Saenz-de-Viteri, Manuel;
Libro:  Catarata y Retina
2017  págs. 73 - 80
Autores: Saenz-de-Viteri, Manuel; García, Alfredo;
Libro:  Casos clínicos en oftalmología. Problemas diagnósticos en patología retinocoroidea
2016  págs. 75 - 76

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