Revistas
Revista:
PATIENT PREFERENCE AND ADHERENCE
ISSN 1177-889X
Vol. 16
Año 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.
Revista:
NUTRIENTS
ISSN 2072-6643
Vol. 13
N° 4
Año 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.
Revista:
NUTRIENTS
ISSN 2072-6643
Vol. 13
N° 5
Año 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.
Revista:
INTERNAL MEDICINE JOURNAL (ONLINE)
ISSN 1445-5994
Vol. 289
N° 1
Año 2021
Págs.116-120
Importance: COVID-19 is caused by SARS-CoV-2, a betacoronavirus that uses the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor to gain entry into cells. ACE2 receptor is widely expressed in multiple organs, including the retina, an extension of the central nervous system. The ACE2 receptor is involved in the diabetic and hypertensive retinopathy. Additionally, coronaviruses cause ocular infections in animals, including retinitis, and optic neuritis.
Objective: To assess whether there is any retinal disease associated with COVID-19.
Design: We have evaluated 27 asymptomatic subjects, with retinal fundoscopic, optical coherence tomography (OCT) and OCT angiography fourteen days after hospital discharge due to COVID-19 bilateral pneumonia.
Results: Cotton wool exudates were evident in six out of 27 patients evaluated, a 22%. Cotton wool exudates are a marker vascular disease severity in other medical context, that is diabetes and hypertension, and are associated with increased risk for acute vascular events. Whether antiaggregation therapy may play a role on fundoscopic-selected patients with COVID-19 requires prospective trials.
Autores:
Udaondo, P. (Autor de correspondencia); Adán, A.; Arias-Barquet, L.; et al.
Revista:
CLINICAL OPHTHALMOLOGY (ONLINE)
ISSN 1177-5483
Vol. 15
Año 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.
Revista:
JOURNAL OF CLINICAL MEDICINE
ISSN 2077-0383
Vol. 10
N° 22
Año 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:
Coco-Martin, R. M.; Andres-Iglesias, C. (Autor de correspondencia); Srivastava, G. K.; et al.
Revista:
SCIENTIFIC REPORTS
ISSN 2045-2322
Vol. 11
N° 1
Año 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.
Revista:
ANTIOXIDANTS
ISSN 2076-3921
Vol. 10
N° 8
Año 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.
Revista:
BIOMEDICINES
ISSN 2227-9059
Vol. 9
N° 5
Año 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:
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
Año 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:
Gegundez-Fernandez, J. A.; Llovet-Osuna, F.; Fernandez-Vigo, J. I. (Autor de correspondencia); et al.
Revista:
ACTA OPHTHALMOLOGICA
ISSN 1755-375X
Vol. 99
N° 7
Año 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.
Revista:
BIOMEDICINES
ISSN 2227-9059
Vol. 9
N° 3
Año 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.
Revista:
ACTA OPHTHALMOLOGICA
ISSN 1755-375X
Vol. 99
N° 8
Año 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.
Revista:
DRUG AND ALCOHOL DEPENDENCE
ISSN 0376-8716
Vol. 229
Año 2021
Background: Myopia is a highly prevalent disorder, and one of the first causes of blindness. In turn, alcohol consumption has been shown to be a risk factor for many diseases and a main contributor to the global burden of disease. However, no studies have investigated the relationship between alcohol intake and myopia. Our aim was to prospectively assess the association between alcohol intake and the development or progression of myopia. Methods: In a Spanish dynamic prospective cohort (the SUN Project) we assessed 15,642 university graduates, recruited between 1999 and 2018 and followed up biennially through mailed questionnaires. Alcohol intake was assessed with a validated 136-item food frequency questionnaire. Development or progression of myopia was collected in subsequent questionnaires during follow-up every two years. Results: Alcohol intake was linearly and significantly associated with a higher risk of myopia development or progression: the OR for 10-year incidence/progression of myopia was 1.05, 95% CI 1.01-1.09 per each 10-grams increase in alcohol intake. Conclusions: Alcohol consumption might lead to the development or progression of myopia, although confirmation is needed for the mechanisms through which this association may occur, thus further research is needed to verify these findings.
Revista:
ANTIOXIDANTS
ISSN 2076-3921
Vol. 9
N° 9
Año 2020
Autores:
de-Andrés-Nogales, F. (Autor de correspondencia); Casado, M. A.; Trillo, J. L.; et al.
Revista:
PHARMACOECONOMICS-OPEN
ISSN 2509-4262
Vol. 4
N° 4
Año 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:
Galvez, M. I. L. (Autor de correspondencia); Barquet, L. A. ; Figueroa, M. S.; et al.
Revista:
ACTA OPHTHALMOLOGICA
ISSN 1755-375X
Vol. 98
N° 7
Año 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.
Revista:
PLOS ONE
ISSN 1932-6203
Vol. 15
N° 7
Año 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:
Minnella, A; Piccardi, M; Placidi, G; et al.
Revista:
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
ISSN 2164-2591
Vol. 9
N° 28
Año 2020
Revista:
EUROPEAN JOURNAL OF OPHTHALMOLOGY
ISSN 1120-6721
Vol. 30
N° 5
Año 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.
Revista:
ANTIOXIDANTS
ISSN 2076-3921
Vol. 9
N° 838
Año 2020
Autores:
Pastor, J. C.; Iglesias, C. A.; Srivastava, G. K. ; et al.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 60
N° 9
Año 2019
Autores:
Camacho-Barcia, L.; Bullo, M. (Autor de correspondencia); Garcia-Gavilan, J. F. ; et al.
Revista:
EUROPEAN JOURNAL OF NUTRITION
ISSN 1436-6207
Vol. 58
N° 2
Año 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.
Revista:
PLOS ONE
ISSN 1932-6203
Vol. 14
N° 10
Año 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:
de Andres-Nogales, F.; Casado, M. A.; Zarranz-Ventura, J.; et al.
Revista:
VALUE IN HEALTH
ISSN 1098-3015
Vol. 22
N° Supl. 3
Año 2019
Págs.S889
Autores:
Kodjikian, L. (Autor de correspondencia); Bellocq, D. ; Bandello, F. ; et al.
Revista:
EUROPEAN JOURNAL OF OPHTHALMOLOGY
ISSN 1120-6721
Vol. 29
N° 6
Año 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.
Revista:
EXPERIMENTAL EYE RESEARCH
ISSN 0014-4835
Vol. 185
Año 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.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 60
N° 9
Año 2019
Revista:
JOURNAL OF OPHTHALMOLOGY
ISSN 2090-004X
Vol. 2019
Año 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:
Ruiz-Medrano, J. ; Montero, J. A.; Flores-Moreno, I.; et al.
Revista:
PROGRESS IN RETINAL AND EYE RESEARCH
ISSN 1350-9462
Vol. 69
Año 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.
Revista:
MOLECULAR THERAPY. METHODS & CLINICAL DEVELOPMENT
ISSN 2329-0501
Vol. 15
Año 2019
Págs.403 - 417
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 60
N° 9
Año 2019
Revista:
ACTA OPHTHALMOLOGICA
ISSN 1755-375X
Vol. 96
N° 2
Año 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.
Revista:
OPHTHALMOLOGICA
ISSN 0030-3755
Vol. 240
N° 2
Año 2018
Págs.61
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 59
N° 9
Año 2018
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 59
N° 9
Año 2018
Revista:
FRONTIERS IN IMMUNOLOGY
ISSN 1664-3224
Vol. 9
Año 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.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 59
N° 9
Año 2018
Revista:
VALUE IN HEALTH
ISSN 1098-3015
Vol. 21
N° Supl. 3
Año 2018
Págs.S432 - S433
Autores:
Camacho-Barcia, M. L.; Bullo, M. ; Garcia-Gavilan, J. F. ; et al.
Revista:
JAMA OPHTHALMOLOGY
ISSN 2168-6165
Vol. 135
N° 6
Año 2017
Págs.657 - 661
IMPORTANCE Cataract, one of the most frequent causes of blindness in developed countries, is strongly associated with aging. The exact mechanisms underlying cataract formation are still unclear, but growing evidence suggests a potential role of inflammatory and oxidative processes. Therefore, antioxidant and anti-inflammatory factors of the diet, such as vitamin K-1, could play a protective role. OBJECTIVE To examine the association between dietary vitamin K-1 intake and the risk of incident cataracts in an elderly Mediterranean population. DESIGN, SETTING, AND PARTICIPANTS A prospective analysis was conducted in 5860 participants from the Prevencion con Dieta Mediterranea Study, a randomized clinical trial executed between 2003 and 2011. Participants were community-dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1) years. MAIN OUTCOMES AND MEASURES Dietary vitamin K-1 intake was evaluated using a validated food frequency questionnaire. The time to the cataract event was calculated as the time between recruitment and the date of the occurrence to cataract surgery, the time to the last visit of the follow-up, date of death, or the end of the study. Hazard ratios and 95% CIs for cataract incidence were estimated with a multivariable Cox proportional hazards model. RESULTS Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n = 1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years follow-up, we documented a total of 768 new cataracts. Participants in the highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P =.002), after adjusting for potential confounders. CONCLUSIONS AND RELEVANCE High intake of dietary vitamin K-1 was associated with a reduced risk of cataracts in an elderly Mediterranean population even after adjusting by other potential confounders.
Revista:
CLINICAL INTERVENTIONS IN AGING (ONLINE)
ISSN 1178-1998
Vol. 12
Año 2017
Págs.1579 - 1587
Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 58
N° 8
Año 2017
Revista:
MOLECULAR THERAPY - NUCLEIC ACIDS
ISSN 2162-2531
Vol. 15
N° 9
Año 2017
Págs.1-11
Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regression of choroidal blood vessels, the hallmark of neovascular age-related macular degeneration. Here, we show that rat pigment epithelial cells can be efficiently transfected with the PEDF-expressing non-viral hyperactive Sleeping Beauty transposon system delivered in a form free of antibiotic resistance marker miniplasmids. The engineered retinal and iris pigment epithelium cells secrete high (141 ± 13 and 222 ± 14 ng) PEDF levels in 72 hr in vitro. In vivo studies showed cell survival and insert expression during at least 4 months. Transplantation of the engineered cells to the subretinal space of a rat model of choroidal neovascularization reduces almost 50% of the development of new vessels.
Revista:
NUTRIENTS
ISSN 2072-6643
Vol. 9
N° 5
Año 2017
Págs.E453
Background: Cataract is a leading cause of vision impairment worldwide, and surgery is the only available treatment. The process that initiates lens opacification is dependent on the oxidative stress experienced by the lens components. A healthy overall dietary pattern, with the potential to reduce oxidative stress, has been suggested as a means to decrease the risk of developing cataract. We aimed to investigate the hypothesis that an intervention with a Mediterranean diet (MedDiet) rather than a low-fat diet could decrease the incidence of cataract surgery in elderly subjects. Methods: We included 5802 men and women (age range: 55-80 years) from the Prevencion con Dieta Mediterronea study (multicenter, parallel-group, randomized controlled clinical trial) who had not undergone cataract surgery. They were randomly assigned to one of three intervention groups: (1) a MedDiet enriched with extra-virgin olive oil (EVOO) (n = 1998); (2) a MedDiet enriched with nuts (n = 1914), and a control group recommended to follow a low-fat diet (n = 1890). The incidence of cataract surgery was recorded yearly during follow-up clinical evaluations. Primary analyses were performed on an intention-to-treat basis. Cox regression analyses were used to assess the relationship between the nutritional intervention and the incidence of cataract surgery. Results: During a follow-up period of 7.0 years (mean follow-up period: 5.7 years; median: 5.9 years), 559 subjects underwent cataract surgery. Two hundred and six participants from the MedDiet + EVOO group, 174 from the MedDiet + Nuts group, and 179 from the control group underwent cataract surgery. We did not observe a reduction in the incidence of cataract surgery in the MedDiet groups compared to the control group. The multivariable adjusted hazard ratios were 1.03 (95% confidence interval [CI]: 0.84-1.26, p = 0.79) for the control group versus the MedDiet + EVOO group and 1.06 (95% CI: 0.86-1.31, p = 0.58) for the control group versus the MedDiet + Nuts group. Conclusions: To our knowledge, this is the first large randomized trial assessing the role of a MedDiet on the incidence of cataract surgery. Our results showed that the incidence of cataract surgery was similar in the MedDiet with EVOO, MedDiet with nuts, and low-fat diet groups. Further studies are necessary to investigate whether a MedDiet could have a preventive role in cataract surgery.
Revista:
NUTRIENTS
ISSN 2072-6643
Vol. 9
N° 10
Año 2017
Págs.1120
In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1 alpha,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 57
N° 12
Año 2016
Págs.271
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 57
N° 12
Año 2016
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 57
N° 12
Año 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.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 57
N° 12
Año 2016
Págs.3696
Purpose : AMD is a leading cause of vision loss among people aged 50 and older. AMD does not lead to total blindness, but the loss of vision interferes with everyday activities. To assess how the main risk factors have an impact on leading the development of the disease, the STARS questionnaire has been tested on the Spanish population
Methods : STARS is 13-scored questions, listing the risk factors having shown the most consistent association with AMD in the literature, for an easy and rapid identification of subjects being at risk for developing AMD.
We performed an epidemiological study (transversal, observational, ecological design) on ¿55 year old subjects recruited from Spanish public hospitals. Subjects were enrolled at clinical discretion. The study was approved by the institutional review board at each site, and written consent was obtained from each subject. All procedures were conforming to the Declaration of Helsinki.
Final statistical analysis was done by logistic multivariate regression model (SAS® software V9.2).
Results : The total recruitment was 7166 subjects (57% females/53% males). A total score, grading the risk of developing AMD, was given by the sum of each risk factor specific score. Fundus examination to detect macular disease was also performed.
After univariate analysis, the main risk factors for AMD were: age, BMI, cardiovascular disease, hypercholesterolemia, family history and cataract surgery history. When multivariate regression was performed age and familiar history were shown as the closest linked to AMD.
After analysis it was also shown that ethnology, dark skin/eye color, myopia/hypermetropia eye condition and fish, vegetable and vegetal oil consumption (>2 portions/month; > 2 portions/week and >2 portions/week) were protective factors.
From the subjects explored by fundus examination showing retinal lesions consistent with AMD: 15% scored<5; 44% scored 5-10 and 40% scored¿10.
Conclusions : The STARS questionnaire could be used in the future as a simple tool to monitor the population at AMD risk. It could be also used to demonstrate that health strategies (dietary ones) can be implemented in order to decrease such risk.
STARS carried out as pilot study, more analysis must be done in order to have more accurate results.
Revista:
BIOCHEMICAL PHARMACOLOGY
ISSN 0006-2952
Vol. 103
Año 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.
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 56
N° 7
Año 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.
Revista:
JOURNAL OF OPHTHALMOLOGY
Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein.
Revista:
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
ISSN 1942-0900
Vol. 2014
N° 637137
Año 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.
Revista:
MOLECULAR VISION
ISSN 1090-0535
Vol. 19
Año 2013
Págs.153-165
Purpose: Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods: Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 mu l) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-a, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results: Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions: These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis.
Revista:
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
ISSN 1672-5123
Vol. 6
N° 6
Año 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.
Revista:
NUTRIENTS
ISSN 2072-6643
Vol. 5
N° 2
Año 2013
Págs.543-551
We studied the macular pigment ocular density (MPOD) in patients with early age macular degeneration (AMD) before and 1 year after nutritional supplementation with lutein and docosahexaenoic acid (DHA). Forty-four patients with AMD were randomly divided into two groups that received placebo (n = 21) or a nutritional supplement (n = 23, 12 mg of lutein and 280 mg of DHA daily). Heterochromatic flicker photometry was used to determine the MPOD. At baseline, the MPOD in AMD patients with placebo was 0.286 +/- 0.017 meanwhile in AMD patients with supplementation it was 0.291 +/- 0.016. One year later, the mean MPOD had increased by 0.059 in the placebo group and by 0.162 in patients receiving lutein and DHA. This difference between groups was significant (p < 0.05). Lutein and DHA supplementation is effective in increasing the MPOD and may aid in prevention of age related macular degeneration.
Revista:
JOURNAL OF CONTROLLED RELEASE
ISSN 0168-3659
Vol. 158
N° 3
Año 2012
Págs.443 - 450
The field of cell microencapsulation is advancing rapidly. Particle size plays a critical role in terms of biocompatibility and limits decisively its applicability. Producing reduced size microcapsules involves broadening the possibilities to employ this technology in the treatment of many disorders. Nervous system diseases (NSD) represent a clear example of that. This work describes the feasibility of reducing the size of alginate-poly-L-lysine-alginate (APA) microcapsules up to 100 ¿m in a highly monodisperse way using the novel Flow Focusing technique. C(2)C(12) myoblasts genetically engineered to express the triple reporter gene thymidine kinase-green fluorescent protein-luciferase (TGL) and secrete vascular endothelial growth factor soluble receptor 2 (VEGFR2, also known as KDR) were encapsulated for further characterization. Resulting new particles were assayed in vitro to explore whether their functionality might be affected due to the physicochemical changes arising from such dramatic size reduction. Not only were negative effects at this level not noticed in terms of cell viability, cell proliferation and KDR secretion, but once again the suitability of APA microcapsules was also reinforced against other microcapsule designs. Furthermore, the fully viable and functional biosystems were successfully administered in the intravitreous space of rats, where the activity of encapsulated cells was monitoring over 3 weeks.
Revista:
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA
ISSN 0365-6691
Vol. 87
N° Suppl. 1
Año 2012
Págs.3 - 9
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 53
N° 3
Año 2012
Págs.1087-94
This study showed for the first time that a particular CFHR1 allotype, CFHR1*A, is strongly associated with AMD (odds ratio, 2.08; 95% confidence interval, 1.59-2.73; P<0.0001) and illustrate a peculiar genotype-phenotype correlation between the CFHR1 alleles and different diseases that may have important implications for understanding the pathophysiology of AMD. It also shows that CFHR1*A is in strong linkage disequilibrium with the CFH 402His allele, which provides additional candidate variants within the major risk haplotype at 1q31, promoting its association with AMD. Further, using the Spanish population as a model, the results showed that analysis of the CFHR1 genotypes provide sufficient information to delineate the individual risk of developing AMD
Revista:
Archivos de la Sociedad Española de Oftalmología
ISSN 0365-6691
Vol. 86
N° 4
Año 2011
Págs.101 - 102
Revista:
INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE
ISSN 0146-0404
Vol. 52
N° 10
Año 2011
Págs.7090 - 7097
TGF-ß inhibition with these peptides represents a promising new therapeutic line for CNV targeting a different pathway than current therapies. More studies are needed to assess this effect on early CNV, alone or in combination with anti-VEGF.
Revista:
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
ISSN 0721-832X
Vol. 248
N° 4
Año 2010
Págs.467 - 476
Objective
To assess the cost-effectiveness of ranibizumab compared with pegaptanib in the treatment of patients with minimally classic/occult neovascular age-related macular degeneration (AMD), from a societal perspective in Spain.
Methods
We constructed a Markov model with five states defined by visual acuity (VA) in the better-seeing eye (Snellen scale): VA >20/40, ¿20/40 to >20/80, ¿20/80 to >20/200, ¿20/200 to >20/400, ¿20/400, and an additional death state. Two cohorts of patients were distributed along the VA states, and treated with either ranibizumab or pegaptanib. Transition probabilities assigned for movement between these states with both drugs were obtained from published randomized clinical trials. Medical costs related to AMD treatment and follow-up, medical costs related to AMD comorbidities, and non-medical-related costs were taken into account. Costs (2008 Euro), health outcomes (Quality-adjusted life years¿QALYs), both discounted at a 3.5% annual rate, and incremental cost-effectiveness ratios (ICER: €/QALY), were determined for a lifetime horizon in the base case analysis. Sensitivity analyses were conducted to explore different scenarios and assumptions in the model.
Results
Treating patients with varying degrees of visual impairment with monthly ranibizumab instead of pegaptanib was €71,206 more costly and provided 2.437 additional QALYs (€29,224/QALY). When administered on an as-needed basis, as in the Prospective Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with Intraocular Ranibizumab (PrONTO) trial, the cost per QALY gained with ranibizumab was reduced to €4,623.
Conclusions
The cost per QALY gained with monthly ranibizumab compared with pegaptanib in the minimally classic/occult neovascular AMD population is just below the €30,000 threshold below which new drugs are sometimes regarded as cost-effective strategies in Spain. In this model, the key variables with greater impact on the cost-effectiveness results were the selected time horizon and the chosen extrapolation method, the source for data on pegaptanib efficacy and the number of ranibizumab injections. When administered on an as-needed basis, ranibizumab was a cost-effective strategy compared to pegaptanib in this population.
Revista:
European journal of ophthalmology
ISSN 1120-6721
Vol. 21
N° 4
Año 2010
Págs.439 - 449
Revista:
EUROPEAN JOURNAL OF OPHTHALMOLOGY
ISSN 1120-6721
Vol. 20
N° 2
Año 2010
Págs.442 - 450
Purpose. To estimate the prevalence and causes of bilateral blindness and visual impairment in an urban institutionalized population aged 65 years and older.
Methods. A total of 392 nursing home residents completed a standardized eye examination, including measurement of visual acuity (VA), intraocular pressure, lens opacity grading, indirect ophthalmoscopy, and photography of the macular area. The major causes of vision loss identified for all participants were blindness and visual impairment.
Results. The average subject age was 82 years (65¿97); women outnumbered men 263 to 129. The prevalence of bilateral blindness (VA ¿1.0 logarithm of the minimum angle of resolution [logMAR]) was 14.9% (43/288); the prevalence of visual impairment (VA ¿0.5 and 1.0 logMAR) was 31.9% (92/288). Blindness and visual impairment increased significantly with age (p<0.05), odds ratio (OR) 1.047 and 1.088, respectively. Cataract was the most common cause of bilateral blindness and visual impairment (27.9% and 44.6%, respectively) followed by pathologic myopia (23.3%) and age-related macular degeneration (AMD) (20.9%) for blindness, and by AMD (27.2%) and pathologic myopia (12%) for visual impairment. Fifty percent of subjects with visual loss had the potential for improved vision with medical or surgical intervention.
Conclusions. Although the prevalences were high, these data are important since it is difficult for epidemiologic studies to include aged, institutionalized individuals, although their numbers are increasing. Recognition of the predominant causes of visual loss dependent on age is fundamental for early diagnosis and treatment of ocular diseases. Many cases of low vision can be treated with appropriate ophthalmologic care.
Autores:
Gómez-Ulla, F; Abraldes, MJ; Basauri, E; et al.
Revista:
Archivos de la Sociedad Española de Oftalmología
ISSN 0365-6691
Vol. 85
N° 9
Año 2010
Págs.294 - 309
