Grupos Investigadores

Líneas de Investigación

  • Búsqueda de biomarcadores de imagen no invasiva para el diagnóstico y tratamiento de enfermedades retinianas
  • Estudios clínicos y genéticos de la aparición y desarrollo de Atrofia Geográfica y/o fibrosis en la DMAE húmeda
  • Evaluación de factores genéticos y ambientales de la Miopía, Miopía Magna y Maculopatía Miópica.
  • Evaluación de nuevas estrategias terapéuticas antioxidantes y antiangiogénicas para patologías retinianas basadas en terapia celular y terapia génica
  • Evaluación de sistemas de liberación controlada para la aplicación de las terapias actuales y terapias alternativas y combinadas
  • Influencia del género en el desarrollo de las patologías retinianas
  • Modelos in vivo e in vitro de patologías retinianas: Degeneración Macular asociada a la Edad, Retinopatía diabética
  • Nuevos sistemas diagnósticos y de predicción de riesgo y desarrollo de DMAE basados en modelos

Palabras Clave

  • Angiogénesis
  • Degeneración Macular Asociada a la Edad
  • Estrés oxidativo y antioxidantes
  • Inflamación
  • Miopía Magna
  • Neovascularización coroidea
  • Retinopatía diabética
  • Terapia celular y génica

Publicaciones Científicas desde 2018

  • Autores: González Zamora, Jorge; Hernández, M. (Autor de correspondencia); Recalde Maestre, Sergio; et al.
    ISSN: 2076-3921 Vol.12 N° 4 2023 págs. 884
    Age-related macular degeneration (AMD) is a leading cause of severe vision loss in older individuals in developed countries. Despite advances in our understanding of AMD, its pathophysiology remains poorly understood. Matrix metalloproteinases (MMPs) have been proposed to play a role in AMD development. In this study, we aimed to characterize MMP-13 in AMD. We used retinal pigment epithelial cells, a murine model of laser-induced choroidal neovascularization, and plasma samples from patients with neovascular AMD to conduct our study. Our results show that MMP13 expression significantly increased under oxidative stress conditions in cultured retinal pigment epithelial cells. In the murine model, MMP13 was overexpressed in both retinal pigment epithelial cells and endothelial cells during choroidal neovascularization. Additionally, the total MMP13 levels in the plasma of patients with neovascular AMD were significantly lower than those in the control group. This suggests a reduced diffusion from the tissues or release from circulating cells in the bloodstream, given that the number and function of monocytes have been reported to be deficient in patients with AMD. Although more studies are needed to elucidate the role of MMP13 in AMD, it could be a promising therapeutic target for treating AMD.
  • Autores: Ruiz-Moreno, J. M. (Autor de correspondencia); Adán, A.; Lafuente, M.; et al.
    ISSN: 0165-5701 Vol.43 N° 12 2023 págs. 4639 - 4649
    Objective: To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies. Methods: This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values. Results: Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 +/- 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 +/- 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 +/- 12.3 letters at baseline to 62.4 +/- 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 +/- 10.2 letters at baseline to 61.5 +/- 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 +/- 135.1 mu m at baseline to 333.4 +/- 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 +/- 2.7 mm(3) at baseline to 9.6 +/- 2.9 mm(3) (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery. Conclusions: In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events.
  • Autores: Zarranz-Ventura, J. (Autor de correspondencia); Bernal-Morales, C.; Sáenz de Viteri Vázquez, Manuel; et al.
    ISSN: 0365-6691 Vol.97 N° 7 2022 págs. 418 - 419
  • Autores: LLorente González, Sara; Hernández, M.; González Zamora, Jorge; et al.
    ISSN: 1755-375X Vol.100 N° 2 2022 págs. e521 - e531
    Purpose To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.
  • Autores: Valdes-Sanz, N.; García Layana, Alfredo; Colas, T.; et al.
    ISSN: 2076-3417 Vol.12 N° 23 2022 págs. 12352
    Background Acute bacterial conjunctivitis (ABC) is a relatively common medical condition caused by different pathogens. Although it rarely threatens vision, it is one of the most common conditions that cause red eyes and may be accompanied by discomfort and discharge. The study aimed to identify and characterize inpatients with ABC treated with topical antibiotics. Methods The EHRead (R) technology, based on natural language processing (NLP) and machine learning, was used to extract and analyze the clinical information in the electronic health records (EHRs) of antibiotic-treated patients with conjunctivitis and admitted to five hospitals in Spain between January 2014 and December 2018. Categorical variables were described by frequency, whereas numerical variables included the mean, standard deviation, median, and quartiles. Results From a source population of 2,071,812 adult patients who attended the participating hospitals in the study period, 11,110 patients diagnosed with acute conjunctivitis were identified. Six thousand five hundred eighty-three patients were treated with antibiotics, comprising the final study population. Microbiology was tested only on 12.1% of patients. Antibiotics, mainly tobramycin, and corticosteroids, mainly dexamethasone, were usually prescribed. NSAIDs were also used in about 50% of patients, always combined with antibiotics. Conclusions The present study provided a realistic representation of the hospital practice concerning managing patients with acute antibiotic-treated conjunctivitis. The diagnosis is usually based on the clinical ground, microbiology is rarely tested, few bacteria species are involved, and local antibiotics are frequently associated with corticosteroids and/or NSAIDs. Moreover, this study provided clinically relevant outcomes, based on new technology, that could be applied in clinical practice.
  • Autores: Calvo-Maroto, A. M. (Autor de correspondencia); LLorente González, Sara; Bezunartea-Bezunartea, J.; et al.
    Revista: CHILDREN
    ISSN: 2227-9067 Vol.9 N° 1 2022 págs. 88
    The main aim of this study was to compare refraction measurements with and without cycloplegia from two refractors devices, (TRK-2P autorefractometer (TRK-2P) and wavefront-based refraction Visionix 130 (VX130)) in children and adolescents. This descriptive observational study included 20 myopic eyes and 40 hyperopic eyes measured in two different Spanish hospitals. Cycloplegia was carried out by three drops of cyclopentolate hydrochloride 1% (Colircusi cycloplegic, Alcon Healthcare S.A., Barcelona). The mean age of the myopia group was 12.40 +/- 3.48 years; for the hyperopia group, the mean age was 7.37 +/- 2.47 years. In the myopia group, autorefraction and wavefront-based refraction did not show clinically significant differences in any components between with and without cycloplegia. The hyperopia group showed statistical and clinically significant differences in sphere and SE components between relaxed and non-relaxed states of accommodation, although the cylindrical components were not clinically different. In this study, we considered a value of >= 0.50D as a clinically significant difference in refraction. Therefore, both devices were capable of obtaining accurate refractions without cyclopegia in myopia children, although they did not avoid instrument myopia and accommodation involved in hyperopia children. Moreover, both refractometers could be useful for astigmatism monitoring in children without the need for cycloplegic drops.
  • Autores: González Zamora, Jorge; Hernández Ruiz de Eguilaz, María (Autor de correspondencia); Recalde Maestre, Sergio; et al.
    ISSN: 2227-9059 Vol.10 N° 7 2022 págs. 1557
    Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10(-/-) mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.
  • Autores: Giocanti-Auregan, A. (Autor de correspondencia); García Layana, Alfredo; Peto, T.; et al.
    ISSN: 1177-889X Vol.16 2022 págs. 587 - 604
    Purpose: Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) patients treated with intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) monotherapies achieve lower vision improvements compared with patients in clinical trials. This qualitative research study aimed to better understand the real-world anti-VEGF treatment experience from nAMD and DME patients', caregivers', and retina specialists' perspectives. Methods: One-time, semi-structured, individual interviews were conducted with adult patients with nAMD or DME treated with antiVEGF injections for >= 12 months, their caregivers, and experienced retina specialists. Interview transcripts were analyzed qualitatively using a thematic analysis approach. Results: A total of 49 nAMD and 46 DME patients, 47 nAMD and 33 DME caregivers, and 62 retina specialists were interviewed in the USA, Canada, France, Germany, Italy and Spain. Most (79%) patients and caregivers reported disruptions to their routine on the day before, the day of, or the day after anti-VEGF injection. Seven nAMD patients (14%) and 14 DME patients (30%) reported having missed an injection visit. The most frequently reported driver for adherence for patients was the doctor-patient relationship (n=66, 70%), whereas for caregivers, it was the ease of booking an appointment (n=25, 32%). Retina specialists reported patient education on the treatment (n=28, 45%) as the most important driver. Treatment barriers could be grouped into four categories: tolerability, clinical factors, logistical parameters and human factors. The most frequently reported barrier to adherence for patients and caregivers was related to side effects (pain/discomfort/irritation: n=63, 67% of patients; n=52, 66% of caregivers), whereas for retina specialists it was logistical parameters (travel logistics: n=44, 71%). Conclusion: This study highlights the importance of the doctor-patient relationship and patient education as key drivers, and treatment tolerability and logistics as key barriers to treatment adherence. Improved doctor-patient relationship/communication and patient education together with new therapies offering convenience, long-acting effectiveness, and better tolerability may improve treatment adherence.
  • Autores: Bilbao Malavé, Valentina; González Zamora, Jorge; Gándara Rodríguez de Campoamor, Elsa Pilar; et al.
    ISSN: 2077-0383 Vol.11 N° 15 2022 págs. 4264
    Myopia is the most common refractive error worldwide. This cannot be explained by genetic factors alone, therefore, environmental factors may play an important role. Hence, the main objective of this study was to analyse whether outdoor exposure could exert a protective effect against the development of myopia in a cohort of young adults and to investigate ultraviolet autofluorescence (CUVAF), as a biomarker of time spent outdoors. A cross-sectional observational study was carried out using two cohorts. A total of 208 participants were recruited, 156 medical students and 52 environmental science students. The data showed that 66.66% of the medical students were myopic, while 50% of the environmental science students were myopic (p = 0.021). Environmental science students spent significantly more hours per week doing outdoor activities than medical students (p < 0.0001), but there was no significant difference with respect to near work activities between them. In both cohorts, the degree of myopia was inversely associated with CUVAF, and a statistically significant positive correlation was observed between spherical equivalent and CUVAF (Pearson's r = 0.248). In conclusion, outdoor activities could reduce the onset and progression of myopia not only in children, but also in young adults. In addition, CUVAF represents an objective, non-invasive biomarker of outdoor exposure that is inversely associated with myopia.
  • Autores: Viola, F.; Kodjikian, L.; García Layana, Alfredo; et al.
    ISSN: 0962-9343 Vol.31 N° Supl. 2 2022 págs. S126
  • Autores: Gegundez-Fernandez, J. A.; Llovet-Osuna, F.; Fernandez-Vigo, J. I. (Autor de correspondencia); et al.
    ISSN: 1755-375X Vol.99 N° 7 2021 págs. e973 - e983
    In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5(th)) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic.
  • Autores: Bilbao Malavé, Valentina; González Zamora, Jorge; de la Puente Carabot, Miriam; et al.
    ISSN: 2076-3921 Vol.10 N° 8 2021 págs. 1170
    Age related macular degeneration (AMD) is the main cause of legal blindness in developed countries. It is a multifactorial disease in which a combination of genetic and environmental factors contributes to increased risk of developing this vision-incapacitating condition. Oxidative stress plays a central role in the pathophysiology of AMD and recent publications have highlighted the importance of mitochondrial dysfunction and endoplasmic reticulum stress in this disease. Although treatment with vascular endothelium growth factor inhibitors have decreased the risk of blindness in patients with the exudative form of AMD, the search for new therapeutic options continues to prevent the loss of photoreceptors and retinal pigment epithelium cells, characteristic of late stage AMD. In this review, we explain how mitochondrial dysfunction and endoplasmic reticulum stress participate in AMD pathogenesis. We also discuss a role of several antioxidants (bile acids, resveratrol, melatonin, humanin, and coenzyme Q10) in amelioration of AMD pathology.
  • Autores: Zarranz Ventura, Javier (Autor de correspondencia); Bernal-Morales, C.; Sáenz de Viteri Vázquez, Manuel; et al.
    ISSN: 0365-6691 Vol.96 N° 8 2021 págs. 399 - 400
  • Autores: Udaondo, P. (Autor de correspondencia); Adán, A.; Arias-Barquet, L.; et al.
    ISSN: 1177-5483 Vol.15 2021 págs. 3183 - 3195
    Purpose: This paper aimed to present daily-practice recommendations for the management of diabetic macular edema (DME) patients based on available scientific evidence and the clinical experience of the consensus panel. Methods: A group of Spanish retina experts agreed to discuss different aspects related with the clinical management of DME patients. Results: Panel was mainly focused on therapeutic objectives in DME management; defini-tion terms; and role of biomarkers as prognostic and predictive factors to intravitreal treatment response. The panel recommends to start DME treatment as soon as possible in those eyes with a visual acuity less than 20/25 (always according to the retina unit capacity). Naive patient was defined, in a strict manner, as a patient who, up to that moment, had never received any treatment. A refractory DME patient may be defined as the one who did not achieve a complete resolution of the disease, regardless of the treatment administered. Different optical coherence tomography biomarkers, such as disorganization of the retinal inner layers, hyperreflective dots, and cysts, have been identified as prognostic factors. Conclusion: This document has sought to lay down a set of recommendations and to identify key issues that may be useful for the daily management of DME patients.
  • Autores: Tabuenca Del Barrio, L. (Autor de correspondencia); Nova-Camacho, L. M.; Zubicoa Eneriz, A.; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.13 N° 21 2021 págs. 5347
    Even today, the mortality rate for uveal melanoma (UM) remains very high. In our research, we sought to determine which pathological and clinical features were correlated with the prognosis of UM. BAP1 (BRCA1-Associated Protein 1) gene mutation has been analyzed as one of the strongest predictors for metastasis in UM. The BAP1 gene codifies the BAP1 protein which has a tumor suppressor function. The presence of this protein can be determined by BAP1 immunohistochemical staining. Eighty-four uveal melanoma patients and forty enucleated eyeballs were examined. Metastasis was present in 24 patients. Nuclear BAP1 staining was low in 23 patients. The presence of a higher large basal diameter tumor (p < 0.001), tumor infiltrating lymphocytes (p = 0.020), and a lack of nuclear BAP1 immunostaining (p = 0.001) ocurred significantly more often in the metastatic group. Metastasis-free survival was lower in patients with low nuclear BAP1 staining (p = 0.003). In conclusion, to the best of our knowledge, this is the first time that BAP1 staining has been studied in uveal melanoma in a Spanish community. We believe that this technique should become routine in the pathological examination of uveal melanoma in order to allow adequate classification of patients and to establish an individual follow-up plan.
  • Autores: Sáenz de Viteri Vázquez, Manuel; Recalde Maestre, Sergio (Autor de correspondencia); Fernández Robredo, Patricia; et al.
    ISSN: 1755-375X Vol.99 N° 8 2021 págs. 861 - 870
    Purpose To assess the effect of fluid status at baseline (BL) and at the end of the loading phase (LP) of three different ranibizumab regimens: treat-and-extend (T&E), fixed bimonthly (FBM) injections and pro re nata (PRN), in patients with neovascular age-related macular degeneration (nAMD). Design Post hoc analysis of the In-Eye study (phase IV clinical trial). Methods Patients were randomized 1:1:1 to the three study arms and were treated accordingly. The presence and type of fluid, intraretinal fluid (IRF) or subretinal fluid (SRF) and the anatomical and visual outcomes were analysed. Main outcome measures Best-corrected visual acuity (BCVA), the mean change from baseline BCVA (BL BCVA), and the proportion of eyes gaining more than 15 letters or losing more than five letters were analysed. Morphological characteristics including the subtype of choroidal neovascular membrane and the development of atrophy and fibrosis were also evaluated. Results Patients with SRF at LP had better visual outcomes than patients with IRF. The persistence of SRF did not affect the mean change from BL BCVA among the three treatment regimens. However, in patients with IRF mean change from BL BCVA was significantly lower in the FBM group. The presence of IRF at BL and at the end of the loading phase was associated with the development of fibrosis at the end of the study; this result was contrary to that observed for patients with SRF. Conclusions While SRF is compatible with good visual and anatomical outcomes, IRF leads to worse results in patients with nAMD; our results suggest that patients with IRF have better outcomes when individualized treatment regimens are used (PRN or T&E) in contrast with a FBM regimen.
  • Autores: Bilbao Malavé, Valentina; González Zamora, Jorge; Sáenz de Viteri Vázquez, Manuel (Autor de correspondencia); et al.
    ISSN: 2227-9059 Vol.9 N° 5 2021 págs. 502
    The purpose of this study was to evaluate the long-term evolution of retinal changes in COVID-19 patients with bilateral pneumonia. A total of 17 COVID-19 patients underwent retinal imaging 6 months after hospital discharge with structural optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The parafoveal retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly thinner in COVID-19 patients at 6 months compared to 0 months (p = <0.001 in both cases). In the optic nerve analysis, a significantly thinner RNFL was observed (p = 0.006) but persisted significantly thickened, compared to controls (p = 0.02). The vascular density (VD) at 6 months persisted significantly decreased when compared to the control group, and no significant differences were found with the 0 months evaluation; in addition, when analyzed separately, women showed a worsening in the VD. Moreover, a significantly greater foveal area zone (FAZ) (p = 0.003) was observed in COVID-19 patients at 6 months, compared to 0 months. The cotton wool spots (CWSs) observed at baseline were no longer present at 6 months, except for one patient that developed new ones. This study demonstrates that some of the previously known microvascular alterations resulting from COVID-19, persist over time and are still evident 6 months after hospital discharge in patients who have suffered from bilateral pneumonia.
  • Autores: Coco-Martin, R. M.; Andres-Iglesias, C. (Autor de correspondencia); Srivastava, G. K.; et al.
    ISSN: 2045-2322 Vol.11 N° 1 2021 págs. 599
    Serious intraocular toxicity cases have been reported worldwide after the use of different perfluorocarbon liquids. The current study reports for the first-time the clinical pictures of cases of acute intraocular toxicity caused by MEROCTANE, a perfluoro-octane commercialized by a Turkish company and distributed in many countries. A series of 18 cases from Chile and Spain was retrospectively analysed. To evaluate the impurity profile, a suspicious MEROCTANE sample (lot OCT.01.2013) was analysed by gas chromatography mass spectrometry and compared with a non-suspicious sample of the same commercial perfluoro-octane (lot OCT 722011). Cytotoxicity was tested following a direct-contact method, taking into consideration the high volatility and hydrophobicity of perfluoro-octane and following the ISO 10993 guideline. Cytotoxicity test showed clear cytotoxic effects of the analysed batch (less than 9% of cell viability). Moreover, chemical analysis demonstrated the presence of many contaminants, some highly toxic (acids and alcohols). Perfluorocarbon liquids are useful tools for intraocular surgery but companies and Agencies of Medical Devices must implement measures that guarantee the safety of these products based on both chemical and cytotoxicity analysis for every batch. Medical staff should be encouraged to report any suspected case to their respective National Agencies.
  • Autores: García Layana, Alfredo; Recalde Maestre, Sergio (Autor de correspondencia); Hernández Sánchez, María; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.13 N° 4 2021 págs. 1253
    The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.
  • Autores: García Layana, Alfredo; Garhoefer, G. (Autor de correspondencia); Aslam, T. M.; et al.
    ISSN: 2077-0383 Vol.10 N° 22 2021 págs. 5432
    Background: Early identification of AMD can lead to prompt and more effective treatment, better outcomes, and better final visual acuity; several risk scores have been devised to determine the individual level of risk for developing AMD. Herein, the Delphi method was used to provide recommendations for daily practice regarding preventive measures and follow-up required for subjects at low, moderate, and high risk of AMD evaluated with the Simplified Test AMD Risk-assessment Scale (STARS(R)) questionnaire. Methods: A steering committee of three experts drafted and refined 25 statements on the approach to be recommended in different clinical situations [general recommendations (n = 2), use of evaluation tools (n = 4), general lifestyle advice (n = 3), and AREDS-based nutritional supplementation (n = 5)] with the help of a group of international experts, all co-authors of this paper. Thirty retinal specialists from Europe and the US were chosen based on relevant publications, clinical expertise, and experience in AMD, who then provided their level of agreement with the statements. Statements for which consensus was not reached were modified and voted upon again. Results: In the first round of voting, consensus was reached for 24 statements. After modification, consensus was then reached for the remaining statement. Conclusion: An interprofessional guideline to support preventive measures in patients at risk of AMD based on STARS(R) scoring has been developed to aid clinicians in daily practice, which will help to optimize preventive care of patients at risk of AMD.
  • Autores: Hernández Sánchez, María (Autor de correspondencia); Recalde Maestre, Sergio; González Zamora, Jorge; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.13 N° 5 2021 págs. 1423
    Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total(R); N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFN gamma in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total(R) protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.
  • Autores: González Zamora, Jorge; Bilbao Malavé, Valentina; Gándara Rodríguez de Campoamor, Elsa Pilar; et al.
    ISSN: 2227-9059 Vol.9 N° 3 2021 págs. 247
    The purpose of this study was to evaluate the presence of retinal and microvascular alterations in COVID-19 patients with bilateral pneumonia due to SARS-COV-2 that required hospital admission and compare this with a cohort of age- and sex-matched controls. COVID-19 bilateral pneumonia patients underwent retinal imaging 14 days after hospital discharge with structural optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) measurements. Vessel density (VD) and foveal avascular zone (FAZ) area were evaluated in the superficial, deep capillary plexus (SCP, DCP), and choriocapillaris (CC). After exclusion criteria, only one eye per patient was selected, and 50 eyes (25 patients and 25 controls) were included in the analysis. COVID-19 patients presented significantly thinner ganglion cell layer (GCL) (p = 0.003) and thicker retinal nerve fiber layer (RNFL) compared to controls (p = 0.048), and this RNFL thickening was greater in COVID-19 cases with cotton wool spots (CWS), when compared with patients without CWS (p = 0.032). In both SCP and DCP, COVID-19 patients presented lower VD in the foveal region (p < 0.001) and a greater FAZ area than controls (p = 0.007). These findings suggest that thrombotic and inflammatory phenomena could be happening in the retina of COVID-19 patients. Further research is warranted to analyze the longitudinal evolution of these changes over time as well as their correlation with disease severity.
  • Autores: Galvez, M. I. L. (Autor de correspondencia); Barquet, L. A. ; Figueroa, M. S.; et al.
    ISSN: 1755-375X Vol.98 N° 7 2020 págs. e820 - e829
    Purpose To assess the noninferiority of the treat-and-extend (T&E) and fixed bimonthly regimens of 0.5 mg intravitreal ranibizumab as compared with the pro re nata (PRN) in naive patients with neovascular age-related macular degeneration (nAMD). Methods Phase IV, randomized, 12-month, multicentre trial. Patients aged >= 50 years with nAMD and visual impairment [best-corrected visual acuity (BCVA) between 23 and 78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] were eligible. Patients (one eye per patient) were randomized to bimonthly, n = 103, T&E, n = 99 or PRN, n = 104. Noninferiority was established at five letters ETDRS. Results The mean (95% CI) difference in BCVA at 12 months was 7.2 (4.2-10.2), 6.4 (2.9-9.8), and 8.0 (51.1-11.0) in the bimonthly, T&E and PRN, respectively. The bimonthly or T&E regimens were not inferior to the PRN scheme. All regimens were associated with a significant reduction of central subfield thickness and volume. The mean (95% CI) number of injections in the bimonthly regimen (7.6, 7.5-7.7) was similar as compared with the PRN regimen (7.4, 6.7-8.0) (p = 0.159) but lower than in the T&E regimen (9.3, 8.9-9.7) (p < 0.001). Conclusion At 12 months, bimonthly and T&E ranibizumab were noninferior to PRN in naive nAMD.
  • Autores: Minnella, A; Piccardi, M; Placidi, G; et al.
    ISSN: 2164-2591 Vol.9 N° 28 2020
  • Autores: de-Andrés-Nogales, F. (Autor de correspondencia); Casado, M. A.; Trillo, J. L.; et al.
    ISSN: 2509-4262 Vol.4 N° 4 2020 págs. 615 - 624
    Background The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) offers the potential to overcome the challenges associated with traditional decision-making tools. Objectives A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. Methods Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defined all of the criteria that could influence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was fitted by applying the backward elimination algorithm (relevant criteria: p value < 0.05). Finally, the results were discussed in a deliberative process (phase C). Results Thirty-one criteria were initially defined (phase A) and grouped into 5 categories: efficacy/effectiveness, safety, organizational and economic impact, patient-reported outcomes, and other therapeutic features. The DCE results (phase B) showed that 10 criteria were relevant to the decision-making process for a 50- to 65-year-old DME patient: mean change in best corrected visual acuity (p value < 0.001), percentage of patients with an improvement of >= 15 letters (p value < 0.001), effect duration per administration (p value = 0.008), retinal detachment (p value < 0.001), endophthalmitis (p value = 0.012), myocardial infarction (p value < 0.001), intravitreal hemorrhage (p value = 0.021), annual treatment cost per patient (p value = 0.001), health-related quality of life (HRQoL) (p value = 0.004), and disability level (p value = 0.021). Conclusions From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment effect duration. It should also contribute to system sustainability by being affordable, it should have a positive impact on HRQoL, and it should prevent disability.
  • Autores: Fernández Robredo, Patricia; González Zamora, Jorge; Recalde Maestre, Sergio; et al.
    ISSN: 2076-3921 Vol.9 N° 838 2020
  • Autores: García Layana, Alfredo (Autor de correspondencia); Adán, A.; Ascaso, F. J.; et al.
    ISSN: 1120-6721 Vol.30 N° 5 2020 págs. 1042 - 1052
    Objective: The aim of this study is to develop guidance on the use of intravitreal dexamethasone implants in the treatment of diabetic macular edema. Method: The study was performed using the modified Delphi method to obtain a consensus among a panel of experts on management of patients with diabetic macular edema and use of intravitreal dexamethasone implants in clinical practice. Thirty-seven panel members, experts on retina, from different Spanish centers were invited to participate. Individual and anonymous opinions were asked by answering a 76-item questionnaire across 11 topic areas (two rounds were done). Level of agreement was assessed using a Likert-type scale of 9 points. Results: Agreement on "consensus" was reached during the first round in 63 items. The 13 remaining items underwent a second round of voting. After the second round, agreement on "consensus" was reached on five items. Finally, eight items remained without consensus. Conclusion: Intravitreal dexamethasone implants are useful in the treatment of patients with diabetic macular edema with different profiles, for example, pseudophakic, poor-adherents, vitrectomized, candidates for cataract surgery, patients with high inflammatory component, and with a history of cardiovascular events. The use of intravitreal dexamethasone reduces the number of visits and facilitates compliance. Experts thought that the switch from anti-vascular endothelial growth factor therapy to intravitreal dexamethasone implants should be done preferably after three injections. Also, pro re nata treatment provides better results in diabetic macular edema patients as it helps to prevent undertreatment. Finally, experts concluded that clinical guidelines and treatment protocols for diabetic macular edema need to be updated.
  • Autores: Bilbao Malavé, Valentina (Autor de correspondencia); Recalde Maestre, Sergio; Bezunartea, J.; et al.
    Revista: PLOS ONE
    ISSN: 1932-6203 Vol.15 N° 7 2020 págs. e0236071
    High myopia and the subsequent degenerative changes of the retina, choroid, and sclera, known as myopic maculopathy (MM), are a serious visual problem in many Asian countries, and are beginning to be so in the south of Europe, especially in the Mediterranean. It is therefore necessary to carry out genetic and environmental studies to determine the possible causes of this disease. This study aims to verify if the genetic factors that have been most related to Asian populations are also associated in two Spanish cohorts. Eight SNPs from six genes (PAX6,SCO2,CCDC102B,BLID,chromosome 15q14, andCOL8A1) along with demographic, ophthalmic and environmental factors were analysed in two cohorts from a total of 365 highly myopic subjects and 177 control subjects. The genetic analysis showed thatCOL8A1SNP rs13095226 was associated with the development of choroidal neovascularization (CNV) and also seems to play an important role in the increase of axial length. The SNP rs634990 ofchromosome 15q14also showed a significant association with MM, although this was lost after the Bonferroni correction. Additional demographic and environmental factors, namely age, sex, smoking status, and pregnancy history, were also found to be associated with MM and CNV in this population.
  • Autores: Sáenz de Viteri Vázquez, Manuel; Hernández, M; Bilbao Malavé, Valentina; et al.
    ISSN: 2076-3921 Vol.9 N° 9 2020
  • Autores: Kodjikian, L. (Autor de correspondencia); Bellocq, D. ; Bandello, F. ; et al.
    ISSN: 1120-6721 Vol.29 N° 6 2019 págs. 573 - 584
    Management of center-involving diabetic macular edema represents a real therapeutic challenge. Diabetic macular edema is the leading cause of visual acuity impairment in diabetic patients. Since the advent of intravitreal drugs, management of diabetic macular edema has significantly evolved. The historical grid laser photocoagulation is no longer recommended as first-line treatment of diabetic macular edema owing to the findings of the pivotal randomized controlled trials, and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids also represent a valid treatment option in the management of naive diabetic macular edema and their efficacy has also been confirmed in several studies. The optimal treatment for diabetic macular edema should consider both general and ophthalmological comorbidities. Patient compliance and motivation should also be carefully evaluated as some treatments require monthly follow-up. Based on recent literature evidence, the present review provides clinicians with a first-line treatment algorithm for center-involving diabetic macular edema tailored to the patient's individual characteristics.
  • Autores: Ruiz-Medrano, J. ; Montero, J. A.; Flores-Moreno, I.; et al.
    ISSN: 1350-9462 Vol.69 2019 págs. 80 - 115
    Myopia is a highly frequent ocular disorder worldwide and pathologic myopia is the 4th most common cause of irreversible blindness in developed countries. Pathologic myopia is especially common in East Asian countries. Ocular alterations associated with pathologic myopia, especially those involving the macular area defined as myopic maculopathy are the leading causes of vision loss in patients with pathologic myopia. High myopia is defined as the presence of a highly negative refractive error ( > -6 to -8 diopters) in the context of eye elongation (26-26.5 mm). Although the terms high myopia and pathologic myopia are often used interchangeably, they do not refer to the same eye disease. The two key factors driving the development of pathologic myopia are: 1) elongation of the axial length and 2) posterior staphyloma. The presence of posterior staphyloma, which is the most common finding in patients with pathologic myopia, is the key differentiating factor between high and pathologic myopia. The occurrence of staphyloma will, in most cases, eventually lead to other conditions such as atrophic, traction, or neovascular maculopathy. Posterior staphyloma is for instance, responsible for the differences between a myopic macular hole (MH)-with and without retinal detachment and idiopathic MH. Posterior staphyloma typically induces retinal layer splitting, leading to foveoschisis in myopic MH, an important differentiating factor between myopic and emmetropic MH. Myopic maculopathy is a highly complex disease and current classification systems do not fully account for the numerous changes that occur in the macula of these patients. Therefore, a more comprehensive classification system is needed, for several important reasons. First, to more precisely define the disease stage to improve follow-up by enabling clinicians to more accurately monitor changes over time, which is essential given the progressive nature of this condition. Second, unification of the currently-available classification systems would establish standardized classification criteria that could be used to compare the findings from international multicentric studies. Finally, a more comprehensive classification system could help to improve our understanding of the genetic origins of this disease, which is clearly relevant given the interchangeable but erroneous use of the terms high and pathologic myopia in genetic research.
  • Autores: Sáenz de Viteri Vázquez, Manuel; Cudrnak, T.
    ISSN: 1029-2403 Vol.60 N° 3 2019 págs. 842 - 844
  • Autores: Recalde Maestre, Sergio; Hernández Sánchez, María; García, L; et al.
    ISSN: 2329-0501 Vol.15 2019 págs. 403 - 417
  • Autores: García Layana, Alfredo (Autor de correspondencia); Garcia-Arumi, J.; Figueroa, M. S. ; et al.
    ISSN: 2090-004X Vol.2019 2019 págs. 9821509
    Purpose. To ascertain wet AMD (wAMD) management patterns in Spain. Methods. A two-round Delphi study conducted through a questionnaire-based survey designed from literature review and validated by an independent Steering Committee. Results. Forty-nine retina specialists experienced in wAMD participated by answering the two-round study questionnaire. Retina specialists are the main responsible for wAMD diagnosis and monitoring, including visits and associated procedures, with a median time per visit of 15 minutes. Standard treatment strategies are based on anti-VEGF administration, including standard loading dose administration followed by maintenance with aflibercept or ranibizumab (81% of patients). Although treat and extend (T&E) dosing strategy is considered as optimal for wAMD management (78% of the panelists), the main routine healthcare limitations (i.e., visits overload, reduced staff, short visit time, coordination issues, lack of facilities) conduct to self-defined "flexible" strategies, based on T&E and pro-re-nata (PRN) protocols. Conclusion. Proactive treatment patterns (T&E) are the preferred ones by the retina specialists in Spain. However, their proper implementation is difficult due to healthcare resource limitations, as well as organisation and logistic issues. The use of anti-VEGF agents with longer duration of action could facilitate the use of strict T&E approaches according to routine clinical practices.
  • Autores: Plaza-Ramos, P. (Autor de correspondencia); Borque, E.; García Layana, Alfredo
    Revista: PLOS ONE
    ISSN: 1932-6203 Vol.14 N° 10 2019 págs. e0223793
    Purpose To evaluate the efficacy and safety of ranibizumab and aflibercept in the treatment of diabetic macular edema in a real world study, and to compare the two treatments with each other. Methods Retrospective observational study of 213 eyes from 141 patients with diabetic macular edema was completed between June 2014 and June 2016. 122 were treated with ranibizumab intravitreal injection and 91 with aflibercept intravitreal injection, with a loading phase of 3 injections and a Pro Re Nata protocol. The drug was selected by the physician and fluorescein angiography was performed by physician's criteria. Re-treatment was performed when a decline in BCVA, an increase of central macular thickness or an increase or persistence of intraretinal fluid in OCT was observed. The primary outcome was the mean change in best corrected visual acuity at 1 year, while central macular thickness, central macular volume, the number of injections and visits were evaluated as secondary outcomes. The correlation between BCVA at 4th month visit and BCVA at 12th month visit was also evaluated. Results The mean baseline best corrected visual acuity for the eyes treated with ranibizumab was 0.55 (+/- 0.35) logMAR, and with aflibercept it was 0.48 (+/- 0.29) (P = 0.109). Best corrected visual acuity improved in both groups, and at the end of the follow-up was 0.40 (+/- 0.35) in the ranibizumab group and 0.40 (+/- 0.29) in the aflibercept group (P = 0.864). Best corrected visual acuity at 4th month visit is correlated at a high value (R = 0.789) with the one at the end of the study. No differences were found in central macular thickness, central macular volume and glycosylated hemoglobin when adjusting with baseline values. The overall number of injections was 5.77 (+/- 2.01), being 5.56 (+/- 2.0) in the ranibizumab group and 6.07 (+/- 1.99) in the aflibercept group (P = 0.069). The main outcome determining final best corrected visual acuity was the baseline best corrected visual acuity (P<0.001). Conclusion There are no differences in efficacy between ranibizumab and aflibercept in diabetic macular edema treatment in this real world study.
  • Autores: Luis de Redín Subirá, Inés; Boiero, C.; Recalde Maestre, Sergio; et al.
    ISSN: 0014-4835 Vol.185 2019
    Corneal neovascularization (CNV) is associated with different ocular pathologies, including infectious keratitis, trachoma or corneal trauma. Pharmacological treatments based on the topical application of anti-VEGF therapies have been shown to be effective in the treatment and prevention of CNV. The aim of this work was to evaluate the effect of bevacizumab-loaded albumin nanoparticles in a rat model of CNV. Bevacizumab-loaded nanoparticles, either "naked" (B-NP) or coated with PEG 35,000 (B-NP-PEG), were administered once a day in the eyes of animals (10 mu L, 4 mg/mL every 24 h) during 7 days. Bevacizumab and dexamethasone were employed as controls and administered at the same dose every 12 h. At the end of the study, the area of the eye affected by neovascularization was about 2-times lower for animals treated with B-NP than with free bevacizumab. In the study, dexamethasone did not demonstrate an inhibitory effect on CNV at the employed dose. All of these results were confirmed by histopathological analysis, which clearly showed that eyes treated with nanoparticles displayed lower levels of fibrosis, inflammation and edema. In summary, the encapsulation of bevacizumab in human serum albumin nanoparticles improved its efficacy in an animal model of CNV.
  • Autores: Ho, I. V. (Autor de correspondencia); Fernández Sanz, Guillermo; Levasseur, S.; et al.
    ISSN: 2162-0989 Vol.8 N° 1 2019 págs. 3 - 7
    Purpose: To evaluate the efficacy and safety of early pars plana vitreetomy (PPV) for the treatment of acute infective endophthalmitis, find identify prognostic factors for better visual outcome. Design: Retrospective cohort study. Methods: Consecutive patients who underwent early PPV within 72 hours of presentation for the treatment of acute infective bacterial endophthalmitis and presented to a large tertiary referral center in New South Wales, Australia, between January 2009 and December 2013 were included. Changes in best-corrected visual acuity (VA) from baseline to 1 year were examined. Results: A total of 64 patients were included. The inciting events were cataract surgery (53%), intravitreal injection (36%), trabeculectomy (3%), and endogenous (3%). The mean VA improved from 3.1 logMAR (hand motion) at baseline to 1.02 (approximately 20/200) at 1 year, with 42% achieving final VA equal to or better than 0.477 logMAR (20/60) following early PPV. Positive prognostic factors were negative microbial cultures (P < 0.01) and etiology of post-cataract surgery (P < 0.01). In multivariable analyses adjusting for age and prognostic factors, patients with baseline VA of light perception and hand motion achieved greater visual gains than those with counting fingers, with gains of logMAR of -2.68, -2.09, and -0.85, respectively (P < 0.0001). Conclusion: Most patients who undergo early PPV experience substantial VA improvement. Negative microbial cultures and endophthalmitis after cataract surgery were associated with better final visual outcome. Patients with presenting VA of light perception or hand motion achieved higher visual gains than those with counting fingers, suggesting the possibility that early PPV may be beneficial in both groups.
  • Autores: Camacho-Barcia, L.; Bullo, M. (Autor de correspondencia); Garcia-Gavilan, J. F. ; et al.
    ISSN: 1436-6207 Vol.58 N° 2 2019 págs. 619 - 627
    ProposalThe aim of this study was to examine the association between the consumption of total and specific types of dairy products and the risk of incident cataracts in an elderly Mediterranean population at high cardiovascular risk.MethodsWe prospectively analyzed 5860 subjects from the PREvencion con DIeta MEDiterranea (PREDIMED) Study. The time to cataract surgery was calculated as the time between recruitment and the date of the surgery, last visit of the follow-up, date of death, or until the end of the study. Dairy products intake was assessed using validated food frequency questionnaires. We used Cox proportional hazard regression to assess the risk of cataract surgery according to average dietary energy-adjusted total dairy products, milk, yogurt and cheese consumption.ResultsWe documented a total of 768 new cataract events after a median of 5.6years of follow-up. Subjects in the second [hazard ratio (HR) 0.62; 95% CI 0.52, 0.74] and third tertile (HR: 0.71; 95% CI 0.60, 0.85) of skimmed yogurt intake had a significantly lower risk of cataracts after adjusting for potential confounders. No significant associations were observed for total dairy products, whole and skimmed milk, whole yogurt and cheese consumption.ConclusionThe intake of skimmed yogurt was associated with a reduced risk of cataracts in an elderly Mediterranean population with high cardiovascular risk. No significant associations were observed for other type of dairy product.Clinical Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.
  • Autores: Barrio Barrio, Jesús (Autor de correspondencia); Bonet Farriol, Elvira; Galdos, M.; et al.
    ISSN: 2090-004X 2019 págs. 7454250
    Introduction. Even though ocular refractive state is highly heritable and under strong genetic control, the identification of susceptibility genes remains a challenge. Several HGF (hepatocyte growth factor) gene variants have been associated with ocular refractive errors and corneal pathology. Purpose. Here, we assess the association of an HGF gene variant, previously reported as associated with hyperopia, and ocular biometric parameters in a multicenter Spanish cohort. Methods. An observational prospective multicenter cross-sectional study was designed, including a total of 403 unrelated subjects comprising 188 hyperopic children (5 to 17years) and 2 control groups: 52 emmetropic adolescents (13 to 17years) and 163 emmetropic young adults (18 to 28years). Each individual underwent a comprehensive eye examination including cycloplegic refraction, and topographic and ocular biometric analysis. Genomic DNA was extracted from oral swabs. HGF single nucleotide polymorphism (SNP) rs12536657 was genotyped. Genotypic, allelic, and logistic regression analyses were performed comparing the different groups. A quantitative trait association test analyzing several biometric parameters was also performed using generalized estimating equations (GEEs) adjusting for age and gender. Results. No association between rs12536657 and hyperopia was found through gender-adjusted logistic regression comparing the hyperopic children with either of the two control groups. Significant associations between mean topographic corneal curvature and rs12536657 for G/A (slope=+0.32; CI 95%: 0.04-0.60; p=0.023) and A/A (slope=+0.76; CI 95%: 0.12-1.40; p=0.020) genotypes were observed with the age- and gender-adjusted univariate GEE model. Both flat and steep corneal topographic meridians were also significantly associated with rs12536657 for the G/A and A/A genotypes. No association was found between rs12536657 and any other topographic or biometric measurements. Conclusions. Our results support a possible role for HGF gene variant rs12536657 in corneal curvature in our population. To our knowledge, this is the first multicenter quantitative trait association study of HGF genotypes and ocular biometric parameters comprising a pediatric cohort.
  • Autores: Fernández Robredo, Patricia; Recalde Maestre, Sergio; Hernandez, M.; et al.
    ISSN: 0146-0404 Vol.60 N° 9 2019
  • Autores: Hernandez, M.; Fernández Robredo, Patricia; Recalde Maestre, Sergio; et al.
    ISSN: 0146-0404 Vol.60 N° 9 2019
  • Autores: Pastor, J. C.; Iglesias, C. A.; Srivastava, G. K. ; et al.
    ISSN: 0146-0404 Vol.60 N° 9 2019
  • Autores: Recalde Maestre, Sergio; Hernandez, M.; Bilbao Malavé, Valentina; et al.
    ISSN: 0146-0404 Vol.60 N° 9 2019
  • Autores: de Andres-Nogales, F.; Casado, M. A.; Zarranz-Ventura, J.; et al.
    Revista: VALUE IN HEALTH
    ISSN: 1098-3015 Vol.22 N° Supl. 3 2019 págs. S889
  • Autores: Guirao Navarro, María Concepción; Sáenz de Viteri Vázquez, Manuel (Autor de correspondencia); Zarranz Ventura, Javier; et al.
    ISSN: 2076-3417 Vol.8 N° 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: Razquin Burillo, Cristina; Ortega Cubero, Sara; Rojo-Bustamante, E.; et al.
    ISSN: 0197-4580 Vol.66 2018 págs. 177.e7 - 177.e10
    The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.31 region (1.4 Mb) in carriers of risk H1 subhaplotypes. We hypothesized that PSP/CBD H1 subhaplotype carriers could have undergone a mutational event absent among unaffected carriers leading to the disease risk. We performed this strategy in definite PSP subjects, definite CBD subjects, and healthy controls and tried to replicate the findings in a larger PSP/CBD case-control series. In the resequencing process, 40 candidate variants were identified, but an association between PSP and rs76970862 was replicated only using an unadjusted model. Gene expression association analysis of this variant suggested no potential functional effect. Although our results failed to identify disease-associated variants, it is still possible that the risk of PSP/CBD at chromosome 17 is driven by rare variants, even in PSP/CBD H1 cases or variants located outside the capture regions. (C) 2018 Elsevier Inc. All rights reserved.
  • Autores: García Layana, Alfredo; Figueroa, MS; Arias, L; et al.
    ISSN: 0030-3755 Vol.240 N° 2 2018 págs. 61
  • Autores: Cobos, E. (Autor de correspondencia); Recalde Maestre, Sergio; Anter, J.; et al.
    ISSN: 1755-375X Vol.96 N° 2 2018 págs. e201 - e212
    PurposeWe sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response to ranibizumab in neovascular age-related macular degeneration (AMD). MethodsA total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from six different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors (gender, smoking habit and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT) and fluid criteria (fluid/no fluid measured by OCT). ResultsHypertension was the environmental factor with the strongest poor response association with ranibizumab in the anatomical measure after the loading phase (p=0.0004; OR 3.7; 95% CI, 2.4-5.8) and after 12months of treatment (p=10(-5); OR 2.3; 95% CI, 1.5-3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a good response, while rs12603486 and rs1136287 (SERPINF1) were associated with a poor response. The protective genotype of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048). ConclusionAll these data suggest that genetics play an important role in treatment response in AMD patients.
  • Autores: Fernández Robredo, Patricia (Autor de correspondencia); Recalde Maestre, Sergio; Hernández Sánchez, María; et al.
    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: Hernández Sánchez, María; Recalde Maestre, Sergio; Zarranz-Ventura, J.; et al.
    ISSN: 0146-0404 Vol.59 N° 9 2018
  • Autores: Fernández Robredo, Patricia; Recalde Maestre, Sergio; Hernández Sánchez, María; et al.
    ISSN: 0146-0404 Vol.59 N° 9 2018
  • Autores: García Layana, Alfredo; Garcia-Arumi, J.; Figueroa, M. S.; et al.
    Revista: VALUE IN HEALTH
    ISSN: 1098-3015 Vol.21 N° Supl. 3 2018 págs. S432 - S433
  • Autores: Recalde Maestre, Sergio; Hernández Sánchez, María; Bezunartea, J.; et al.
    ISSN: 0146-0404 Vol.59 N° 9 2018
  • Autores: Sáenz de Viteri Vázquez, Manuel; González Zamora, Jorge
    Libro: Inteligencia artificial en retina. Monografía
    ISSN: 978-84-09-18591-7 2020 págs. 19 - 30
  • Autores: García Layana, Alfredo; Sáenz de Viteri Vázquez, Manuel
    Libro: Manual de retina SERV
    ISSN: 978-84-9113-564-7 2019 págs. 219 - 232

Proyectos desde 2018

  • Título: Enfermedades Inflamatorias
    Código de expediente: RD21/0002/0010
    Investigador principal: ALFREDO GARCIA LAYANA.
    Convocatoria: 2021 AES Redes de Investigación cooperativa orientadas a resultados (RICORS)
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2024
    Importe concedido: 180.537,50€
    Otros fondos: Fondos FEDER
  • Título: Miopía vs Miopía patológica ¿dos procesos diferentes? Del exoma al estilo de vida. MYoriGENE Study
    Código de expediente: PI20/00251
    Investigador principal: SERGIO RECALDE MAESTRE.
    Convocatoria: 2020 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2024
    Importe concedido: 92.565,00€
    Otros fondos: Fondos FEDER
  • Título: Caracterización de los puntos hiperreflectivos como biomarcador en OCT en patologías retinianas. Estudio clínico y experimental (Con-OCT)
    Código de expediente: PI18/00314
    Investigador principal: PATRICIA FERNANDEZ ROBREDO.
    Convocatoria: AES2018 PI
    Fecha de inicio: 01-01-2019
    Fecha fin: 30-06-2023
    Importe concedido: 183.920,00€
    Otros fondos: Fondos FEDER
  • Título: Red temática enfermedades oculares
    Código de expediente: RD16/0008/0011
    Investigador principal: JAVIER MORENO MONTAÑES.
    Convocatoria: 2016 AES REDES
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2022
    Importe concedido: 118.470,00€
    Otros fondos: Fondos FEDER
  • Título: Análisis de la superficie ocular en pacientes con glaucoma crónico y su relación con las alteraciones de las glándulas de Meibomio y la producción mucínica.
    Código de expediente: PI14/00811
    Investigador principal: JAVIER MORENO MONTAÑES.
    Convocatoria: 2014 ISCIII Proyectos de I+D
    Fecha de inicio: 01-01-2015
    Fecha fin: 30-06-2019
    Importe concedido: 59.895,00€
    Otros fondos: -