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Background:Rapid and effective remission-inducing therapy is mandatory in uveitis to avoid irreversible structural and functional damage. In some severe cases biological agents might be required (1-6).High-dose intravenous methylprednisolone (IVMP) may achieve prompt control of inflammation in most immune mediated inflammatory diseases (IMID), including non-infectious uveitis (NIU).Objectives:To evaluate the efficacy and safety of IVMP pulse therapy in NIU of different IMID.Methods:Multicentre study of 71 patients with severe uveitis who received IVMP. The underlying diseases were: Vogt Koyanagy Harada disease (VKHD) (n=24), Behçet disease (BD) (19), Sarcoidosis (5) and idiopathic NIU (23). The main outcome variable was Best-Corrected Visual Acuity (BCVA) estimated using the Snellen chart. BCVA that was assessed at 0 (basal), 2-5, 7, 15 and 30 days after IVMP.The results are expressed as mean ±SD in normally distributed variables, or as median [IQR] when are not. Comparison of continuous variables was performed using the Wilcoxon test.Results:We studied 46♀/ 25♂ patients. The main features are shown in Table 1. IVMP dose ranged from 250 to 1000 mg/day administered for 3-5 consecutive days, the dose was established according to the presence or not of other systemic manifestations apart from uveitis. All of them had active intraocular inflammation at the moment of the study. BCVA values improved considerably after 1 month (Figure 1). No major side effects were observed.Figure 1.Improvement of best corrected visual acuity (BCVA).Conclusion:High-dose IVMP pulse therapy is useful and safe for a prompt control of BCVA regardless of the underlying IMID.References:[1]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94. doi: 10.1016/j.ajo.2018.12.019[2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. PMID: 25005576[3]Santos-Gómez M, et al. Clin Exp Rheumatol. 2016;34(6 Suppl 102): S34-S40. PMID:27054359[4]Atienza-Mateo B, et al. Rheumatology (Oxford) 2018;57(5):856-864. doi: 10.1093/rheumatology/kex480.[5]Atienza-Mateo B, et al. Arthritis Rheumatol. 2019; 71(12):2081-2089. doi: 10.1002/art.41026.[6]Martín-Varillas JL, et al. Ophthalmology. 2018;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020Table 1.Main features of 71 patients with NIU. Data are of affected eyes.VKHD(n=24)Idiophatic(n=23)Behcet’s disease (n=19)Sarcoidosis(n=5)Overall(n=71)Men/Women, n5/199/149/102/371Mean age (years) ±SD42 ±1147 ± 1533±1042 ± 22-Unilateral/Bilateral NIU, n (%)2 (8.3)/22(91.7)10 (43.5)/13(56.5)4 (21)/15 (79)3(60)/2(40)19/52NIU patterns, n (%) Posterior uveitis6 (25)9 (39.1)3 (15.8)1 (20)19 Panuveitis18 (75)14 (60.9)16 (84.2)4 (80)52Laboratory data, n (%) ANA2 (8.34)2 (8.7)0 (0)1 (20)5 HLA B270 (0)4 (17.4)0 (0)0 (0)4 HLA B290 (0)1 (4.3)0 (0)0 (0)1 HLA B510 (0)5 (21.7)8 (42)3 (60)16 Angiotensin Converting Enzyme (ACE)1 (4.17)2 (8.7)0 (0)1 (20)4Disclosure of Interests:None declared

Background:Cystoid Macular Edema (CME) is the most important cause of blindness in non-infectious uveitis (NIU) (1). Corticosteroids and conventional and/or biological immunosuppressant may be required (1-6). High-dose intravenous methylprednisolone (IVMP) pulse therapy may induce a rapid improvement.Objectives:To evaluate the efficacy and safety of IVMP pulse therapy in CME of different immune mediated inflammatory diseases (IMID).Methods:Multicentre study of 66 patients with severe ocular inflammation who received IVMP. The underlying diseases were: Vogt Koyanagy Harada disease (VKHD)(n=24), Behçet’s disease (BD) (19) and idiopathic NIU (23). The main outcome variable was macular thickness and macular edema (Optical coherence tomography [OCT] >300 μm); that was assessed at 0 (basal), 2-5, 7, 15 and 30 days after IVMP.The results are expressed as mean ±SD for normally distributed variables, or as median [IQR] when are not. Comparison of continuous variables was performed using the Wilcoxon test.Results:We studied 43♀/ 23♂ patients. The main features are shown in TABLE 1. IVMP dose ranged from 250 to 1000 mg/day administered for 3-5 consecutive days, the dose was established according to the presence or not of other systemic manifestations apart from uveitis. All of them had active intraocular inflammation at the moment of the study.Table 1.Main features of 66 patients with cystoid macular edema.VKHD(n=24)Idiophatic(n=23)Behcet’s disease(n=19)Overall(n=66)Men/Women, n5/199/149/1066Mean age (years)42 ± 1147 ± 1533 ± 10-Unilateral/Bilateral, n (%)2 (8.3) /22 (91.7)10 (43.5) /13 (56.5)4 (21) /15 (79)16/50Inflammatory ocular patterns, n (%) Posterior uveitis6 (25)9 (39.1)3 (15.8)18 Panuveitis18 (75)14 (60.9)16 (84.2)48Laboratory data, n (%) ANA2 (8.34)2 (8.7)0 (0)4 HLA B270 (0)4 (17.4)0 (0)4 HLA B290 (0)1 (4.3)0 (0)1 HLA B510 (0)5 (21.7)8 (42)13A rapid and maintained statistically improvement was observed in OCT values in all underlying diseases (FIGURE 1). No major side effects were observed.Conclusion:High-dose IVMP pulse therapy is useful and safe in the prompt control of CME, regardless of the underlying IMID.References:[1]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94. doi: 10.1016/j.ajo.2018.12.019.[2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. PMID: 25005576.[3]Santos-Gómez M, et al. Clin Exp Rheumatol. 2016;34(6 Suppl 102): S34-S40. PMID:27054359.[4]Atienza-Mateo B, et al. Rheumatology (Oxford) 2018;57(5):856-864. doi: 10.1093/rheumatology/kex480.[5]Atienza-Mateo B, et al. Arthritis Rheumatol. 2019; 71(12):2081-2089. doi: 10.1002/art.41026.[6]Martín-Varillas JL, et al. Ophthalmology. 2018;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020.Figure 1.Improvement of OCT in 66 patients with cystoid macular edema.Disclosure of Interests:None declared

Background In uveitis rapid and effective remission-inducing therapy is mandatory to avoid irreversible damage. Objectives To evaluate the efficacy and safety of high-dose intravenous methylprednisolone (IVMP) pulse therapy in uveitis. Methods Multicentre study of 129 patients (203 eyes) with uveitis who received IVMP. The underlying diseases were: Idiopathic (n=30), Vogt Koyanagy Harada,29 Behcet disease,19 Sarcoidosis,6 Multifocal Choroidopathy,4 Birdshot chorioretinopathy,2 Acute posterior multifocal placoid pigment epitheliopathy,1 Granulomatosis with polyangiitis,2 Aortitis,1 Immune thrombocytopenic purpura,1 Rheumatoid arthritis,2 Axial Spondylitis,6 Psoriatic arthritis,2 Juvenile Idiopathic Arthritis,1 Thrombophilia synd.,1 Eales Disease,2 Sympathetic Ophthalmia,2 Multiple Sclerosis,2 Relapsing Polychondritis,1 Cogan’s synd.,1 Sjogren synd.,2 Crohn’s disease,1 Reactive arthritis,1 Toxic oil synd. and brain ischemia,1 Raynaud’s Disease and brain ischemia,1 Pseudotumor,1 Cataract surgery,1Herpes Simplex,1Varicella Zoster-associated acute retinal necrosis,1T.pallidum3 and M.tuberculosis.1 The inflammatory ocular patterns were: panuveitis (66), posterior uveitis (PU),31 intermediate uveitis (IU),5 anterior uveitis (AU),12 AU and PU,2 AU and IU,1 IU and PU,1 exudative retinal detachment,3 vasculitis,4 pseudotumor,1 scleritis2 and sclero-uveitis.1 Bilateral ocular involvement was observed in 74 cases. Patients were assessed at basal visit and day 2–5, 7, 15 and 30 after IVMP. The main outcome variable was best corrected visual acuity (BCVA), the degree of inflammation of the anterior chamber and vitreous, and macular thickness (macular oedema defined by OCT >300 µm). The results are expressed as mean ±SD for normally distributed variables, or as median [interquartile range] when are not. Comparison of continuous variables was performed using the Wilcoxon test. Results We studied 74 x/55 x; mean age 42±14.3 years. IVMP dose ranged from 40–1000 mg/day for 3–5 consecutive days. Prior to IVMP, cycloplegic and corticosteroid eye drops were used in all cases. Improvement was faster among patients with inflammation in anterior chamber and vitritis than in BCVA, CME, retinitis and retinal vasculitis (TABLE). Total remission was achieved in 19.4% of the 129 patients after IVMP. In 126 of the patients continued with oral corticosteroids and 4 received an intraocular dose of steroids. These immunosuppressive drugs were added: Methotrexate (52), Cyclosporine A,48 Azathioprine40 and others.5 In a few cases biological therapy (64) was administered afterwards. In general, acute respiratory infection was the side-effect most frequent. Conclusions High-dose IVMP pulse therapy is beneficial in the prompt control of severe uveitis and it is well tolerated. Disclosure of Interest None declared

This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan(©) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition.

Resumen Fundamentos No esta establecida de forma definitiva la importancia de los factores de riesgo vascular (FRV) y del estado de hipercoagulabilidad en los pacientes con obstruccion venosa retiniana (OVR). Objetivos Analizar la importancia de los FRV, la prevalencia de trombofilia y los hallazgos ecograficos en los troncos supraaorticos en los pacientes con OVR. Pacientes y metodo Estudio prospectivo de todos los pacientes con OVR remitidos a una consulta de Medicina Interna. Se analizaron las variables clinicas, de laboratorio (incluido un estudio de trombofilia) y ecograficas. Resultados Se estudiaron 98 pacientes (56 varones y 42 mujeres) con una media de edad de 66 anos. La hipertension y la dislipemia fueron los FRV mas prevalentes. Tenian hiperhomocistinemia un 24% y presentaban placas de ateroma en los troncos supraaorticos el 48%. La OVR fue periferica en 69 y central en 29. En un 13% se detecto una trombofilia genetica y en un 9% adquirida. En los sujetos menores de 50 anos la trombofilia se observo en el 50% y en los que no tenian FRV en el 67% (p = 0,004). El 77% recibieron antiagregantes. Siete estaban anticoagulados por fibrilacion auricular y ello no evito la aparicion de la OVR. En 4 casos se inicio anticoagulacion que se mantuvo de forma indefinida en los 3 pacientes con sindrome antifosfolipido. Conclusiones En los pacientes con OVR parece recomendable el control de los FRV clasicos y la determinacion de los niveles de homocisteina. Nuestros datos sugieren ademas, descartar la presencia de un sindrome antifosfolipido, y solamente en los sujetos menores de 50 anos o sin FRV se podria considerar un estudio de trombofilia. La antiagregacion con aspirina es el tratamiento recomendado para reducir el riesgo vascular global, y solo se consideraria la anticoagulacion en aquellos con trombofilias de mayor potencial trombotico.

This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan(©) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition.

OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS: Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS: No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION: Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.

Objective:Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes.Methods:Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin.Results:A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (PFDR=5.07E-03, OR=1.48, CI 95%=1.14-1.92 and PFDR=3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients.Conclusion:Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies. © 2013 Márquez et al.

Background Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. Methods A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. Results A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P- value=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. Conclusion Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility., The authors thank Sofía Vargas, Sonia Rodríguez and Gema Robledo (from Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, Spain) for their excellent technical assistance, and all the patients and healthy controls for kindly accepting their essential collaboration. Banco Nacional de ADN (University of Salamanca, Spain) and Biobanco Vasco para la Investigación (Fundación Vasca de Innovación e Investigación Sanitarias, Bizkaia, Spain) are thanked for supplying part of the samples.

The importance of vascular risk factors (VRF) and hypercoagulable state in patients with retinal vein occlusion (RVO) has not been conclusively established.To analyze the relevance of VRF, prevalence of thrombophilia, and ultrasonography findings in the supra-aortic trunks in patients with RVO.A prospective study was performed of all the patients diagnosed of RVO referred to an Internal Medicine clinic. The clinical, laboratory (including a thrombophilia panel) and ultrasonographic variables were analyzed.A total of 98 patients (56 men, 42 women) mean age 66 years, were studied. Hypertension and dyslipidemia were the most prevalent VRF. Of these, 24% had hyperhomocysteinemia and atherosclerotic plaques were detected in the supra-aortic trunks in 48%. RVO was peripheral in 69 and central in 29. Genetic thrombophilia was detected in 13% and it was acquired in 9%. Thrombophilia was observed in 50% of subjects aged50 years and in 67% of those without VRF (P=.004). Seventy-seven percent received antiplatelet drugs. Seven were on anticoagulants due to atrial fibrillation, although this did not prevent the development of RVO. Anticoagulation treatment was initiated in 4 cases, this being maintained indefinitely in the three patients diagnosed with antiphospholipid syndrome.In patients with RVO, it may be recommendable to control classical VRF and measure serum homocysteine levels. Our data also suggest that antiphospholipid syndrome should be ruled out and that a study of thrombophilia should only be considered in subjects aged50 years or without VRF. Antiplatelet therapy with aspirin is the treatment of choice to reduce the overall vascular risk. Anticoagulation should only be considered in those patients with high-risk thrombophilias.

During development of multicellular organisms, cells become differentiated by modulating different programs of gene expression. Cells have their own epigenetic signature which reflects genotype, developmental history, and environmental influences, and it is ultimately reflected in the phenotype of the cells and the organism. However, in normal development or disease situations, such as adaptation to climate change or during in vitro culture, some cells undergo major epigenetic reprogramming involving the removal of epigenetic marks in the nuclei followed by the establishment of a different new set of marks. Compared with animal cells, biotech-mediated achievements are reduced in plants despite the presence of cell polypotency. In forestry, any sustainable developments using biotech tools remain restricted to the lab, without progressing to the field for application. Such barriers in the translation between development and implementation need to be addressed by organizations that have the power to integrate these two fields. However, a lack of understanding of gene regulation is also to blame for this barrier. In recent years, great progress has been made in unraveling the control of gene expression. These advances are discussed in this chapter, including the possibility of applying this knowledge in forestry practice.

In vitro culture is one of the most studied techniques, and it is used to study many developmental processes, especially in forestry species, because of growth timing and easy manipulation. Epigenetics has been shown as an important influence on many research analyses such as cancer in mammals and developmental processes in plants such as flowering, but regarding in vitro culture, techniques to study DNA methylation or chromatin modifications were mainly limited to identify somaclonal variation of the micropropagated material. Because in vitro culture is not only a way to generate plant material but also a bunch of differentially induced developmental processes, an approach of techniques and some research carried out to study the different changes regarding DNA methylation and chromatin and translational modifications that take place during these processes is reviewed.

The evolution of the incidence and the epidemiology of ocular candidiasis in our hospital during the past 12 y, as well as the factors associated with poor functional outcome were analysed. A retrospective study of all cases of ocular candidiasis admitted to a university hospital between 1993 and 2004 was performed. Epidemiological, clinical and final outcome data were recorded. 37 episodes of ocular candidiasis in 36 patients were studied. 28 (75%) episodes occurred between 1993 and 1998 (13.09 episodes/100,000 admissions/y), and all of these patients were intravenous drug users. In contrast, only 9 episodes of ocular candidiasis were recorded between 1999 and 2004 (4.42 episodes/100,000 admissions/y; p.0001) and 3 (33%) patients were not drug users (p0.01). 19 (57%) cases had final visual acuity0.1. Treatment with conventional amphotericin B instead of other newer antifungal drugs was associated with poor visual prognosis in the univariate (p = 0.03) and multivariate (p = 0.03) analysis. In conclusion, the incidence of ocular candidiasis has decreased significantly in recent y and the epidemiology has changed. Currently, one-third of patients are immunocompromised non-drug users. Therapy with conventional amphotericin B instead of newer antifungal drugs appears to be associated with a poorer functional outcome.

Background Intense ocular inflammation can cause an early and irreversible structural and functional damage. Objectives Treatment with high-dose intravenous methylprednisolone (IVMP) can induce a rapid improvement in multiple inflammatory conditions including uveitis. Methods A multicenter study of 104 patients (169 eyes) with severe ocular inflammation treated with IVMP attended in uveitis units of 11 hospitals. The most frequent underlying syndromes were: idiopathic uveitis (n=21), Vogt-Koyanagi-Harada (n=26), Behcet (n=19), spondyloarthritis (n=4), Sjogren syndrome (n=2), psoriatic arthritis (n=2) and multiple Sclerosis (n=2). The patients were evaluated at baseline and on days 2-5, 7, 15 and 30 after treatment with IVMP. Results 104 patients (59 women/45 men) were studied with a mean age of 42.27±14.42 years (range 8-76 years) receiving doses of IVMP, which ranged from 0.25 to 1 gram per day for 2-5 consecutive days. They all had active and severe intraocular inflammation at baseline. The inflammatory ocular patterns were: panuveitis (n=61), posterior uveitis (n=35), anterior uveitis (n=3), scleritis (n=3) and intermediate uveitis (n=2). Bilateral ocular involvement was observed in 65 patients (62.5%). After IVMP treatment, the inflammation of the anterior chamber, the vitritis and visual acuity experienced rapid and statistically significant improvement from the second day. However, the improvement of retinal vasculitis, choroiditis/chorio-retinitis and macular edema was more slowly achieved, gaining statistical significance from the first week. Optical coherence tomography (OCT) showed a macular thickening (>250μ) in 90 eyes at baseline, with normalization in 30% of affected eyes at day 15 and in 50% of affected eyes at day 30 (p Conclusions Our study suggests that IVMP is an effective and safe remission induction therapy in severe ocular inflammation. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4735

Objectives To assess the efficacy and safety of Golimumab in patients with refractory uveitis to other anti-TNFα drugs. Methods Study of patients from a single center with refractory uveitis to previous standard synthetic immunosuppressive drugs and at least 1 anti-TNFα drug. Golimumab was given at the standard dose of 50 mg/sc/month. Results A total of 25 patients (39 affected eyes) (19 men/6 women); mean age, 32.5±8.9 years (range 11-47); fulfilled the above-mentioned criteria. In 14 cases uveitis was bilateral and in 11 cases it was unilateral. The underlying diseases were spondylarthritis (n=7), psoriatic arthropathy (n=4), juvenile idiopathic arthritis (n=4), sarcoidosis (n=3), Behcet disease (n=2), uveitis associated with HLA-B27 and ulcerative colitis (n=1), pars planitis (n=1) and Vogt-Koyanagi-Harada (n=1). Besides oral steroids and before Golimumab onset they had received: intraocular corticosteroids (n=10), methylprednisolone i.v. boluses (n=6), methotrexate (n=20), cyclosporine A (n=6), azathioprine (n=6), adalimumab (n=17), infliximab (n=14), abatacept (n=2) and certolizumab (n=1). Golimumab was started because inefficacy (n=23) and/or toxicity (n=2) to other biologics. Golimumab was used as monotherapy (n=9) or in combination with methotrexate (n=9), azathioprine (n=3), leflunomide (n=2) and mycophenolate (n=2). There was a rapid (from 1st week) and maintained (1st year) improvement of visual acuity, anterior chamber inflammation, vitritis and OCT. The mean OCT improved from 319.9±77.9 μm (baseline) to 270.2±54.8 μm (1st month) (p Conclusions Golimumab seems an effective and safe treatment for those patients with uveitis even refractory to other anti-TNFα drugs. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4758

Objectives To assess the efficacy and safety of anti-TNFα drugs in refractory uveitis to conventional synthetic immunosuppressive drugs (CSISDs). Methods Study of refractory uveitis from a single Universitary hospital who had failed to at least one CSISD. The degree of ocular inflammation was established according to SUN-2005. Macular thickness was evaluated by OCT. We compared data between baseline 1st month, and 1st, 2nd, 3rd and 4th year (Wilcoxon test). Results We studied 40 adult patients/62 affected eyes (16 men/24 women); mean age, 39.3±11.5 years. The underlying pathologies were Spondyloarthritis-HLA-B27+ (n=7), Behcet disease (n=6), sarcoidosis (n=6), VKH (n=2), Birdshot (n=1), serpinginous (n=1), sympathic opthalmopathy (n=1), Juvenile Idiopathic Arthritis (n=1) and idiopathic uveitis (n=15). Besides oral corticosteroids and before anti-TNFα, patients had received methylprednisolone i.v. (n=9), methotrexate (n=16), cyclosporine A (n=13) and azathioprine (n=10). The first anti-TNFα was: adalimumab (n=18; 45%) (40 mg/sc/2 weeks) and infliximab (n=22; 55%) (5 mg/kg/i.v./every 4-8 weeks. Anti-TNFα drugs were used as monotherapy (n=8), or combined with methotrexate (n=18), azathioprine (n=10), Cyclosporine A (n=3) and salazopyrine (n=1). Adalimumab was switched to golimumab (50 mg/sc/week) (n=2) and to tocilizumab (n=2). Infliximab was switched to adalimumab (n=8) and to golimumab (n=2). Visual acuity (VA), Tyndall, vitritis and OCT experienced significant improvement at the 1st month, and 1st, 2nd and 3rd year. The mean OCT in cases of cystoid macular edema (OCT>300 μ) (n=11 eyes) improved from 382.2±98.4 (baseline) to 195.5±38.9 microns (1st year). After a mean follow-up of 40.7±25 months anti-TNFα drugs was well tolerated in most cases. The most important side effects were pulmonary TBC (n=1), herpes zoster (n=2), urinary tract infection (n=3) and elevation of liver enzymes during treatment (n=2). Conclusions Anti-TNFα therapy seems effective and relatively safe in refractory uveitis. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3369

The actual methods to evaluate total DNA methylation based on high performance liquid chromatography (HPLC) are long and tedious due to the specific running buffers required. In this work, a new open-tube capillary electrophoresis system has been applied to the separation of acid hydrolyzed genomic DNA and so, to the evaluation of genomic DNA methylation. Several running conditions were tested but separation of cytosine and 5-methyl-cytosine was only possible by sodium dodecyl sulfate (SDS) micelle system. The importance of sample dissolution preparation has also been demonstrated. The results of this study open up the possibility of quantification of the relative methylation degree of rapid genomic DNA by a simple method based on high performance capillary electrophoresis (HPCE).

Background Increased incidence of syphilis has been observed in developed countries in the last decade. In some cases uveitis indistinguishable from that related to non-infectious autoimmune uveitis may be the presenting manifestation of syphilis. Objectives From a wide series of patients with syphilitic uveitis our aims were: 1) To describe the clinical features and visual outcomes. 2) To assess differences with syphilitic patients without uveitis in demographic features, HIV status, viral load and CD4 count and cerebrospinal fluid findings. Methods Retrospective and comparative case series study. Since year 2000, 50 patients (19 females/31 males) with 45±17 years were diagnosed as having syphilitic uveitis in 8 centers from Spain. Other 86 randomly selected syphilitic patients without uveitis diagnosed in the same centers during the same period were included. Clinical and laboratory data were collected from the clinical records. Continuous variables (normally and not normally distributed) were compared with the 2-tailed Student’ Results The most frequent anatomic uveitic pattern was posterior; 26 (52%) cases. Granulomatous inflammation of the anterior chamber was observed in 3 (6%) patients. Several types of posterior segment inflammation were observed: optic neuritis (40%), vitritis (35%), necrotizing retinopathy (35%), retinal vasculitis (20%), posterior placoid chorioretinitis (10%), multifocal chorioretinitis (10%), macular edema (7.5%), serous retinal detachment (5%), neuroretinitis (5%), multifocal choroiditis (2.5%). Mean ± SD initial visual acuity (VA) of right and left eyes (RE, LE) was 0.43±0.37 and 0.49±0.37 respectively. After a mean follow-up of 27.1±3 months final VA was statistically better in both eyes (RE: 0.72±0.34; p=0.012 and LE: 0.75±0.33; p=0.012). We did not find differences in syphilitic patients with and without uveitis in age and sex distribution. We observed more frequently homosexual and HIV+ patients in the group of uveitis (p=0.002 and p=0.032). HIV patients from both groups did not presented differences in CD4 count and viral load. Patients with uveitis had higher amount of cells in cerebrospinal fluid: 5 (0-10400) vs 1 (0-50) p=0.020. No differences were observed in the concentration of proteins and frequency of positive serology. Conclusions We observed an increased incidence of syphilis presenting as uveitis in our Uveitis Units. High level of suspicion for this infection is required to establish an early diagnosis and appropriate treatment. In this relatively large series of patients with syphilitic uveitis, posterior uveitis was the most frequent type of uveitis. Prognosis was favourable in terms of VA. Patients with syphilitic uveitis presented more frequently homosexual practices, HIV+ and presented a greater number of cells in the cerebrospinal fluid. Disclosure of Interest None Declared

Objectives To assess the efficacy of Infliximab (IFX) and adalimumab (ADA) in refractory uveitis of Behcet’s syndrome. Methods Study of 63 patients followed in the Uveitis Clinic of 24 hospitals. All of them were refractory to conventional therapy with systemic steroids and ≥1 immunosuppressive drug. Efficacy was evaluated according to SUN criteria, and macular thickness by optical coherence tomography (OCT). Outcomes and comparisons were made at week 1, week 2, month 1, month 6 and at 1 and 2 years. Statistical analyses were performed using the STATISTICA (Statsoft). Results were expressed: mean±1SD (normally distributed variables) or median [25th-75th interquartile range-IQR] (not normally). Continuous variables were compared with the Wilcoxon test. Results We studied 63 patients/110 affected eyes (36M, 27W), mean age 38.9±9.0 years. Prior to anti-TNF, patients had received ivMprednisolone (n=20), cyclosporine (CyA) (n=53), methotrexate (MTX) (n=31) and azathioprine (AZA) (n=30). IFX was the anti-TNF more commonly used (64%). The remaining patients (36%) were treated with ADA. 14 patients (22%) required switching (12 from IFX→ADA; 2 ADA→IFX). Dosage: IFX 5 mg/kg/iv every 4-8 weeks or ADA 40 mgsc/2weeks. The median[IQR] follow-up from the onset of anti-TNF was 36 [20-60] months. Significant improvement of Visual acuity (VA), Tyndall and vitritis was observed soon (week 1). At 2 years,VA improved from 0.5±0.3 at basal to 0.7±0.3 (p Conclusions Monoclonal anti-TNF therapy is effective and relatively safe in uveitis of Behcet’s syndrome refractory to conventional therapy. Disclosure of Interest None Declared

Growth and the chlorophyll and carotenoid contents were measured in greenhouse-grown yellow nutsedge (Cyperus esculentusL. ♯ CYPES), following treatment with glyphosate [N-(phosphonomethyl)glycine]. Herbicide was applied as a foliar spray at concentrations of 0.1, 1.0, 5.0, and 10.0 mM. After 2 weeks, growth was inhibited, and chlorosis and leaf apex necrosis were observed. Plant height was reduced, leaf fresh weight was decreased by 40%, and leaf dry weight was slightly affected. Rhizome, tuber, and secondary shoot formation was strongly inhibited, but root development was not affected by glyphosate treatment. With the 10-mM treatment, dry weight of the underground system was reduced by 80%. Chlorophyll and carotenoid levels were decreased by 52 and 54%, respectively, following glyphosate treatment.