New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

Silicone oil droplets in repackaged anti-vascular endothelial growth factors for intravitreal injections: In search of the main source of contamination.

INTRODUCTION: Repackaging of anti-vascular endothelial growth factors in polypropylene syringes lubricated with silicone oil for intravitreal use is associated with the presence of intravitreal silicone oil droplets. The objective of this study is to assess how the use of silicone-free syringes (for storage and/or administration) would reduce the amount of silicone oil droplets in the product to be administered. METHODS: Two 16 mL vials of bevacizumab were repackaged at the compounding pharmacy to obtain four sets of product, each consisting of three 1.2 mL tubes of the drug repackaged in different ways. Set A was repackaged according to routine practice, that is, the drug was placed into 1 mL siliconized syringes and 60 µL aliquots were extracted with 0.5 mL insulin siliconized syringes until reaching 1.2 mL. In set B, a 1-mL silicone-free syringe was used, followed by a 0.5 mL siliconized syringe. In set C, only 0.5 mL siliconized syringes were used. In set D, only the 1-mL silicone-free syringe was used. Micro-Flow Imaging technology was used for quantifying silicone oil droplet-like particles below 25 µm. RESULTS: Silicone oil droplet-like particles were absent in set D. Set C had the highest average frequency of these particles, which was much lower in sets A and B. Set B had the lowest frequency. CONCLUSION: 0.5 mL insulin syringes with staked-in needles used for supplying the product seem to be the main source of silicone oil contamination in repackaged anti-vascular endothelial growth factors. Silicone-free insulin syringes with staked-in needles would be strongly recommended for supplying anti-vascular endothelial growth factor intravitreal injections from compounding pharmacies.

Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma.

PURPOSE: To evaluate photodynamic therapy (PDT) for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN: Prospective, multicenter, nonrandomized clinical trial. PARTICIPANTS: Thirty-one eyes of 31 patients with posterior pole CCH and symptoms caused by exudation into the macular area. INTERVENTION: Photodynamic therapy was applied by Zeiss laser. Intravenous verteporfin at 6 mg/m(2) body surface was administered before treatment, and light emitted at 689 nm for photosensitization. The treatment spot diameter was calculated on early-phase frames of pretreatment indocyanine green angiography. Fifteen minutes after starting the verteporfin infusion, the laser beam was applied to the retina at radiant exposure 50 J/cm(2) and exposure time 83 seconds. One to 4 treatments were applied at 12-week intervals over 1 year. Standardized evaluation was performed before and at 4-week intervals after each treatment, and at 3, 6, 9, and 12 months. All patients were followed for >or=12 months. MAIN OUTCOME MEASURES: The primary outcome measure was the absence of exudative retinal detachment at the 12-month follow-up visit on ophthalmoscopy, fluorescein angiography, and optical coherence tomography. Secondary measures were the visual acuity outcome, with best-corrected visual acuity determined by the Early Treatment for Diabetic Retinopathy Study chart, tumor thickness decrease on B-scan ultrasonography, and adverse events. RESULTS: Among the total, 82.8% of patients required 1, 13.8% 2, and 3.4% 3 PDTs to eliminate exudative retinal detachment. Visual acuity increased from a mean of 20/60 to 20/35 (P<0.001). Sixty-nine percent of patients demonstrated visual recovery (P<0.001). Cystoid macular edema regressed in all cases and exudative macular detachment disappeared in all but 2 cases. The CCH thickness decreased in all cases from a mean of 3.0 to 1.7 mm, with the most intense effect seen after 4 weeks of treatment (P<0.001). Visual fields showed resolution of central scotomas. There were no severe adverse events. CONCLUSIONS: Combining PDT with the standard age-related macular degeneration protocol is an effective treatment for CCH in terms of resolution of exudative subretinal fluid and recovery of VA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Specific association of IL17A genetic variants with panuveitis.

BACKGROUND/AIMS: A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to non-anterior uveitis and its main clinical subgroups. METHODS: Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls. RESULTS: The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis. CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology. SUBTITLE: Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.

Estimation of antioxidants dietary intake in wet age-related macular degeneration patients.

AIMS: The aim of this study was to estimate the intake of antioxidant nutrients in wet age-related macular degeneration (AMD) patients, a degenerative and progressive disorder of the macula, which is the central part of the retina, associated with central vision loss. METHODS: A sample (n = 52, 78.9 ± 6.6 years old, 40.4% females and 59.6% males) of patients diagnosed of AMD was interviewed. Anthropometric measurements, two 24- h recalls, a semi-quantitative food frequency questionnaire and a general questionnaire incorporating questions related to socio-demographic and lifestyle variables were used. RESULTS: Most of wet AMD patients showed inadequate antioxidant nutrient intake (< 2/3 of Recommended Dietary Intake, RDI), and more than 60% of patients showed serious deficient intake (< 1/3 RDI) of lutein and zeaxanthin. Most consumed antioxidant rich foods only represented low contributions to antioxidant intake. Although adiposity is a factor risk for AMD progression; the fat and saturated fatty acids (SFA) intake of study participants were higher than the recommendations; the prevalence of overweight was 61.9% men and 58.1% in women; and 83% of patients (90.5% men and 77.4% women) showed fat mass over the cut-off limits. CONCLUSIONS: The food pattern of wet AMD patients should be improved by means of an increase in the consumption of antioxidant rich foods, and a decrease in SFA rich foods.L.

Objetivos: El objetivo de este estudio fue estimar la ingesta de nutrientes antioxidantes en pacientes con degeneración macular asociada a la edad (AMD) variedad húmeda, un trastorno degenerativo y progresivo de la mácula, la parte central de la retina, asociada con la pérdida de la visión central. Métodos: En una muestra de pacientes diagnosticados de AMD (n = 52, 78,9 ± 6,6 años, 40,4% mujeres y 59,6% hombres) se registraron medidas antropométricas, dos recordatorios de 24 h, un cuestionario semicuantitativo de frecuencia de consumo de alimentos y cuestiones sociodemográficas y de estilo de vida. Resultados: La mayoría de los pacientes con AMD húmeda mostraron una ingesta inadecuada de nutrientes antioxidantes (< 2/3 de las Ingestas Dietéticas Recomendadas, RDI) y más de 60% de los pacientes mostraron un déficit grave (< 1/3 RDI) de luteína y zeaxantina. Los alimentos ricos en antioxidantes más consumidos sólo aportaron bajas contribuciones a la ingesta de antioxidantes. Aunque la adiposidad es un factor de riesgo para la progresión de la AMD, el consumo de grasas y ácidos grasos saturados (SFA) de los pacientes fueron superiores a las recomendaciones; la prevalencia de sobrepeso fue del 61,9% hombres y 58.1% en las mujeres; y el 83% de los pacientes (90,5% hombres y 77,4% mujeres) mostró una masa grasa superior a los límites. Conclusiones: El patrón alimentario de los pacientes con AMD debería mejorarse aumentando el consumo de alimentos ricos en antioxidantes y disminuyendo los alimentos ricos en SFA.

Patients with neovascular age-related macular degeneration in Spain display a high cardiovascular risk.

PURPOSE: Cardiovascular disease and its risk factors may have a significant role in the development of neovascular age-related macular degeneration (NV-AMD). This study aims to assess the impact of these factors in this population and define their level of cardiovascular risk according to the Framingham model. METHODS: This was a cross-sectional, observational, multicenter study that included patients aged 50 years or older who attended ophthalmic centers for the diagnosis or follow-up of NV-AMD. Information collected included demographic and AMD data, a complete history of cardiovascular disease and its risk factors, lipid profile, blood pressure, and treatment history. RESULTS: The study population consisted of 901 patients, predominantly Caucasian, with a mean age of 75.7 years, receiving anti-vascular endothelial growth factor therapy for their NV-AMD in 77.7% of the cases. Blood pressure measurement during the study visit and lipid analyses revealed poor control in 67.7% and 93.3% of the patients, respectively. Hypertension was the most prevalent cardiovascular risk factor (77.7%), followed by a history of cardiac disease or other forms of atherosclerotic disease (53.8%). Diabetes was present in 28% of the subjects. The study population was considered a high-risk population according to the National Cholesterol Education Program Expert Panel Clinical Guidelines (NCEP ATP III), with a probability of a cardiovascular event in 10 years of 19.3% according to the Framingham model. CONCLUSIONS: This NV-AMD population is associated with a significant cardiovascular risk, and the Framingham model can help us identify those subjects with higher risk levels in order to improve their overall management.