Background Evaluating the efficacy and refractoriness to treatment and determining factors associated with adverse outcomes in uveitis associated with spondylarthritis (SpA) are complicated by the lack of validated outcome measures. Objectives The aims of this study were to develop an outcome score SpA-U in patients with uveitis associated with SpA and to determine factors associated with adverse outcomes in patients with uveitis under systemic treatment. Methods The outcome score SpA-U was defined by best-corrected visual acuity, anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their SEs are displayed together with linear regression coefficients with 95% confidence intervals. For continuous factors, averages and SDs are reported in addition to linear regression coefficients with 95% confidence interval. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex. Results One hundred ninety-seven uveitis outbreaks were included. Sixty-two uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history (β = 0.34), axial and peripheral involvement (β = 0.43), Ankylosing Spondylitis Disease Activity Score >2.1 (β = 0.45), positive HLA-B27 (β = 0.29), female sex (β = 0.19), patients with C-reactive protein elevation (β = 0.002), and bilateral ocular involvement (β = 0.32). At the same time, shorter disease evolution (β = −0.02) was associated with less severe uveitis activity. Conclusion We have determined factors associated with adverse outcomes in patients with uveitis associated with SpA by developing an outcome score SpA-U that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment.

Analizar la prevalencia de signos tomográficos no exudativos (signo de cebolla, seudoedema, tubulación de la retina externa, seudoquistes, hendiduras subretinianas y atrofia macular) en pacientes con degeneración macular asociada a la edad neovascular. Un total de 174 ojos de pacientes con degeneración macular asociada a la edad neovascular que no habían recibido tratamiento previo fueron incluidos en el estudio. Se valoró la agudeza visual, la actividad de la neovascularización y la aparición o no de los distintos signos objeto de estudio en los tiempos 0 (visita inicial), 4 meses, un año, año y medio y a los 2 y 3 años de seguimiento. Se evaluaron también: la edad, el sexo, el ojo afecto y el tipo de neovascularización (1, 2, 3, polipoidea o mixta). Los análisis se han realizado mediante el software estadístico R (versión 3.3.2) y el paquete glmmADMB (versión 0.8.3.3). La presencia de seudoquistes y tubulación de la retina externa va en aumento a lo largo del seguimiento. El signo de cebolla comienza con una frecuencia ascendente hasta los 12 meses, posteriormente desciende a los 18 meses y vuelve a incrementarse a los 24 meses. En cuanto al seudoedema, mantiene un incremento hasta los 18 meses para finalmente descender. Las hendiduras subretinianas son el signo más raro, presentándose en el 1,1% en la primera visita. Finalmente, la atrofia macular, presente en el 12,6% de los ojos inicialmente, se encuentra en el 25% a los 2 años. Los seudoquistes, la tubulación de la retina externa y la atrofia macular fueron los signos más prevalentes, mientras que las hendiduras subretinianas fueron los más infrecuentes. To analyze the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration. A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3). The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years. Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent.

the main cause of blindness in non-infectious uveitis is cystoid macular edema (CME). Behçet’s disease (BD) is one of the most common diseases associated with CME [1-3].to compare efficacy and safety of Adalimumab (ADA), Infliximab (IFX) and Certolizumab (CZP) in refractory CME due to BD.multicenter study of patients with CME secondary to BD refractory to glucocorticoids (GC) and at least 1 conventional immunosuppressant. All patients had CME (OCT>300µ) at baseline. From baseline up to 2 years, efficacy of ADA, IFX and CZP was assessed with the following ocular parameters: macular thickness (µm), visual acuity (BCVA), anterior chamber (AC) cells, vitritis and GC-sparing effect. Statistical analysis was performed with IBM SPSS Statistics v.23.a total of 50 patients (78 eyes) were considered. Twenty-five patients were treated with ADA, 15 patients with IFX and 10 patients were treated with CZP. No significant differences in demographic parameters were observed in the three groups. However, patients in the CZP group had a significantly longer time from diagnosis to drug initiation (75 [36-120] vs 30 [12-82] vs 15 [8-60] months; p=0.04) and received a greater median number of biological treatments (2 [0.75-3] vs 0 [0-0] vs 0 [0-0]) than the ADA and IFX groups. In CZP group, ADA and IFX were used previously in 7 patients. Combined therapy was used with ADA in 64%, with IFX in 66.7% and with CZP in 70% of CZP patients (p=0.94) (TABLE 1).Regarding efficacy outcomes, a rapid and maintained improvement in macular thickness was observed after 2 years of follow-up in three groups with no statistically significant differences between them (FIGURE 1). Improvement in BCVA, AC cells, vitritis and a GC-sparing effect was also noted. No serious adverse events were observed in IFX and CZP group. One case of pyelonephritis was reported in the ADA group.ADA, IFX and CZP seem to be effective and safe in refractory CME due to BD. CZP appears effective even in patients with inadequate response to ADA and/or IFX.[1]Martín-Varillas JL, et al. J Rheumatol. 2021;48:741-750.[2]Martín-Varillas JL, et al. Ophthalmology 2018; 125:1444-1451.[3]Martín-Varillas JL, et al. RMD Open 2022;8:e002693.Table 1.Main characteristics of CME-BD patients receiving adalimumab (ADA), infliximab (IFX) or Certolizumab (CZP).ADAgroup(n=25)IFXgroup(n=15)CZPgroup(n=10)PAge, mean (SD) years41 (11)38 (9)36 (8)0.34Sex, men/women, n/n12/137/83/70.61HLA-B51 positive, n(%)19 (76)10 (67)4 (40)0.13Duration of uveitis before treatment, median30 [12-82]15 [8-60]75 [36-120]0.04Unilateral, n(%)10 (40)9 (60)3 (30)0.28Pattern of uveitis, n(%)Anterior0 (0)0 (0)2 (20)–Intermediate0 (0)0 (0)1 (10)0.13Posterior5 (20)5 (33.3)3 (30)0.62Panuveitis20 (80)10 (66.7)4 (40)0.07Ocular outcomes at the time of anti-TNF beginningAC cells (Tyndall), median [IQR]2 [1-3]1 [0-1]1 [0-2]0.15Vitritis, median [IQR]3 [1-3]1 [0-2]1 [0-2]0.03BCVA, mean (SD)0.41±0.240.33±0.220.48±0.180.17Macular thickness, mean (SD)431.9±117.6483.4±126.1380.7±96.50.08Previous conventional treatment, n (%)IV pulses of MTP13 (52)9 (60)5 (50)0.85Cyclosporine A22 (88)11 (73.3)6 (60)0.17Azathioprine14 (56)8 (53.3)4 (40)0.69Methotrexate

OBJECTIVE:To analyse the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration.MATERIAL AND METHODS:A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3).RESULTS:The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years.CONCLUSION:Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent.

OBJECTIVES Rapid control of intraocular inflammation in non-infectious uveitis (NIU) is mandatory to avoid irreversible structural and functional damage. In this study, we assessed the efficacy and safety of intravenous methylprednisolone (IVMP) pulses in the treatment of NIU. METHODS A retrospective case series of 112 patients who received IVMP for the treatment of NIU, either isolated or associated with different underlying diseases, was studied. Intraocular inflammation (anterior chamber cells and vitritis) was the primary outcome measure. Secondary outcome measures were macular thickness and best corrected visual acuity (BCVA). Patients were assessed at baseline visit, and at days 2-5, 7, 15 and 30 after initiation of IVMP pulse therapy. RESULTS A total of 112 patients (mean age 42±14.5 yrs) were assessed. An underlying immune-mediated disease was diagnosed in 73 patients. Inflammatory ocular patterns were panuveitis (n=68), posterior uveitis (n=30), anterior uveitis (AU) (n=12), and intermediate uveitis (n=2). Additionally, patients presented cystoid macular oedema (CME) (n=50), retinal vasculitis (n=37), and exudative retinal detachment (n=31). Therapies used before IVMP included intraocular glucocorticoids (n=4), high-dose oral systemic glucocorticoids (n=77), and conventional (n=107) or biologic (n=40) immunosuppressive drugs. IVMP dose ranged from 80 to 1,000 mg/day for 3-5 consecutive days. Improvement was observed in AU, vitritis, BCVA, CME, and retinal vasculitis. At first month evaluation, total remission was achieved in 19 patients. Side effects of IVMP were respiratory infections (n=3), uncontrolled hyperglycaemia (n=1), herpes zoster (n=1), and oral candidiasis (n=1). CONCLUSIONS IVMP pulse therapy was effective and safe, and achieved rapid control of NIU.

Background Adalimumab remains the only biologic approved by the EMA and FDA for the treatment of non-infectious uveitis [1-6]. The reports on efficacy of other anti-TNF drugs such as Certolizumab Pegol (CZP) are scarce. Objectives to determine the efficacy and safety of CZP in refractory uveitis secondary to Immune-mediated Inflammatory Diseases (IMIDs). Methods national multicenter study of 80 patients with uveitis due to IMID refractory to glucocorticoids and conventional immunosuppressants treated with CZP. Efficacy was assessed with the following ocular parameters: best corrected visual acuity (BCVA), anterior chamber cells, vitritis, macular thickness and presence of retinal vasculitis. The efficacy of CZP was compared between the baseline visit, 1 st week, 1 st and 6 th month, and 1 st year. Statistical analysis was performed with IBM SPSS Statistics v.23. Results we studied 80 patients/111 affected eyes (33 men/47 women) with a mean age of 41.6±11.7 years. The IMIDs included were: spondyloarthritis (n=43), Behçet’s disease (10), psoriatic arthritis (8), Crohn’s disease (4), sarcoidosis (2), JIA (1), reactive arthritis (1), rheumatoid arthritis (1), relapsing polychondritis (1), TINU (1), pars planitis (1), Birdshot (1) and idiopathic uveitis (6). Anterior was the most frequent uveitis pattern (n=61). In 20 patients, besides the presence of refractory uveitis, desire of pregnancy was the reason for CZP initiation. Prior to CZP, patients had received: methotrexate (n=38), sulfasalazine (28), azathioprine (14), cyclosporine (10), leflunomide (3), mycophenolate mofetil (4), and cyclophosphamide (1). Previous biologic therapy was administered in 52 patients (63%), with a median [IQR] of 2 [1-3] drugs per patient. The most used biologic was adalimumab (n=48), followed by infliximab (32), golimumab (15), tocilizumab (5), etanercept (7), rituximab (1), anakinra (1) and secukinumab (1). CZP was administered as monotherapy in 39 patients. After 24 [12-36] months of follow-up, all parameters analyzed showed a rapid and maintained improvement (Table 1). A decrease in the mean number of uveitis flares was observed before and after CZP, (2.6±2.3 vs. 0.6±0.4, p<0.001). CZP was discontinued in 16 patients due to: ocular remission (n=3), insufficient ocular response (4) and incomplete response of extraocular manifestations (9). No serious adverse effects were found. Table 1. main ocular parameters analyzed in 80 patients with uveitis due to IMID and treated with CZP. Baseline 1st week 1st month 3rd month 6th month 1st year BCVA (mean±SD) 0.68±0.27 0.73±0.26* 0.79±0.26* 0.82±0.25* 0.85±0.24* 0.86±0.23* Tyndall improvement , n (%) Patients with Tyndall + at baseline (n=57 ) - 23 (40.3) 45 (78.9) 47 (82.4) 57 (100) 57 (100) Vitritis improvement , n (%) Patients with Vitritis at baseline (n=14 ) - 5 (35.7) 8 (57.1) 13 (92.8) 14 (100) 14 (100) OCT (µm) (mean±SD) 297.5±48.1 297.1±45.5 286.5±39.8* 277.6±43.3* 271.5±38.6* 269.0±38.8* Choroiditis, affected eyes , n (%) 3 (2.4) 3 (2.4) 2 (1.6) 2 (1.6) 1 (0.8) 1 (0.8) Retinal vasculitis, affected eyes , n (%) 3 (2.4) 2 (1.6) 1 (0.8) 0 (0) 0 (0) 0 (0) *p<0.01 Conclusion CZP seems to be effective and safe in the control of uveitis associated to different IMIDs. References [1]Jaffe GJ, et al. N Engl J Med 2016;375:932-43. doi: 10.1056/NEJMoa1509852. [2]Nguyen QD, et al. Lancet 2016;388:1183-92. doi: 10.1016/S0140-6736(16)31339-3. [3]Martín-Varillas JL, et al. Ophthalmology 2018; 125:1444-1451 doi: 10.1016/j.ophtha.2018.02.020 [4]Martín-Varillas JL, et al. J Rheumatol. 2021;48:741-750. doi: 10.3899/jrheum.200300 [5]Atienza-Mateo B. Arthritis Rheumatol. 2019;71:2081-2089. doi: 10.1002/art.41026. [6]Vegas-Revenga N et al Am J Ophthalmol. 2019;200:85-94. doi: 10.1016/j.ajo.2018.12.019 Disclosure of Interests None declared

Background: Prognosis of non-infectious refractory uveitis has improved markedly with biologic therapy (BT) (1-5 ). Most data are with monoclonal anti-TNF drugs, especially Adalimumab (ADA) and Infliximab (IFX). However, there is not enough evidence for the use of Certolizumab Pegol (CZP). Objectives: To evaluate the efficacy and safety of CZP in refractory uveitis secondary to Immune-Mediated Inflammatory Diseases (IMID). Methods: Multicenter study of 71 patients with uveitis due to IMID refractory to glucocorticoids and conventional immunosuppressants. Efficacy was assessed with the following ocular parameters: best corrected visual acuity (BCVA), anterior chamber cells, vitritis, macular thickness and presence of retinal vasculitis. These outcomes were compared between baseline, 1st week, 1st and 6th month, and 1st and 2nd year. Statistical analysis was performed with IBM SPSS Statistics v.23. Results: 71 patients/100 affected eyes (29 men/42 women) with mean age of 40.0±11.3 years were studied. Underlying IMIDs were: spondyloarthritis (n=38), Behçet (10), psoriatic arthritis (8), Crohn disease (3), sarcoidosis (2), JIA (1), reactive arthritis (1), rheumatoid arthritis (1), relapsing polychondritis (1), TINU (1), pars planitis (1), Birdshot (1) and idiopathic uveitis (3). Uveitis pattern was anterior (n=55), posterior (6), panuveitis (6) and intermediate (4). Prior to CZP, patients had received: methotrexate (37), sulfasalazine (26), azathioprine (14), cyclosporine (10), leflunomide (3), mycophenolate mofetil (3) and cyclophosphamide (1). Previous BT was administered in 48 (67.6%) patients, with a mean of 1.4±1.3 drugs per patient as follows: ADA (n=56), IFX (27), golimumab (14), tocilizumab (5) and etanercept (3). Pregnancy was the reason for prescribing CZP in 19 patients. CZP was administered in monotherapy (n=39) or combined with conventional immunosuppressants (n=32). After a mean follow-up of 27.1±21.1 months, most of the ocular variables showed a rapid and significantly improvement (Table 1). A decrease in the median number [IQR] of flares of uveitis before and after CZP, (3 [1-4] vs. 0 [0-1], p<0.001) was observed. CZP was discontinued in 15 patients due to remission (n=2), ocular insufficient response (2) and incomplete response of extraocular manifestations (11). No serious adverse events were reported. Conclusion: CZP seems to be effective and safe in patients with refractory uveitis due to IMID. References: [1]Martín-Varillas JL, et al. Ophthalmology 2018; 125:1444-1451. doi: 10.1016/j.ophtha.2018.02.020. [2]Atienza-Mateo B, et al. Arthritis Rheumatol 2019; 71:2081-2089. doi: 10.1002/art.41026. [3]Santos-Gómez M, et al. Clin Exp Rheumatol 2016; 34(6 Suppl 102):S34-S40. PMID: 27054359 [4]Vegas-Revenga N, et al. Am J Ophthalmol 2019; 200:85-94. doi: 10.1016/j.ajo.2018.12.019 [5]Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32 (4 Suppl 84):S54-7. PMID: 25005576 Table 1. Baseline 1 st week 1 st Month 6 th Month 1 st year 2 nd year BCVA (mean±SD) 0.68±0.27 0.72±0.27* 0.79±0.25* 0.84±0.24* 0.85±0.25* 0.87±0.22* Improvement in AC Cells, n (%) Patients with AC cells at baseline (n=48 ) - 21 (43.7) 30 (62.5)* 41 (85.4)* 48 (100)* 48 (100)* Improvement in Vitritis, n (%) Patients with vitritis at baseline (n=13 ) - 3 (23.1) 8 (61.5)* 11 (84.6)* 13 (100)* 13 (100)* OCT (µ ) (mean±SD) 292.5±47.7 294±47.4 286.7±41.9* 274.7±38.7* 272.8±38.9* 266.31±36.2* Choroiditis; affected eyes, n, (%) 3 (4.2) 3 (4.2) 2 (2.8) 2 (2.8) 1 (1.4) 0 (0) Retinal Vasculitis; affected eyes, n, (%) 2 (2.8) 0 (0) 1 (1.4) 0 (0) 0 (0) 0 (0) *p<0.001 Disclosure of Interests: None declared

OBJECTIVESAnti-IL6R tocilizumab (TCZ) therapy has proved to be useful in the treatment of refractory ocular and/or neurological involvement of Behçet's disease (BD). However, TCZ efficacy in other BD manifestations remains unclear. In this study we aimed to assess the efficacy of TCZ in the different clinical phenotypes of BD.METHODSThis is a multicentre study of BD patients treated with TCZ, due to refractivity to standard systemic treatment.RESULTSWe studied 16 patients (10 men/6 women); mean age 36.5±18.2 years. The main clinical manifestations at TCZ onset were ocular, oral and/or genital ulcers, arthritis, folliculitis and/or neurological involvement. Before TCZ, they had received several conventional and/or biological immunosuppressants, such as methotrexate, cyclosporine, adalimumab or infliximab. TCZ was used in monotherapy or combined with conventional immunosuppressive drugs. The main indications for TCZ prescription were refractory uveitis (n=14) and refractory neurobehçet (n=2). After a median [IQR] follow-up of 20 [9-45] months using TCZ, neurological and ocular domains improved in most cases with complete remission in most patients with uveitis. Articular and peripheral venous manifestations also experienced a favourable evolution. However, oral/genital ulcers, skin lesions and intestinal manifestations followed a torpid course.CONCLUSIONSTCZ is effective in BD with major clinical involvement. However, it does not seem to be effective in oral/genital ulcers or skin lesions.

Background:Anti-TNFα agents are useful in uveitis(1-5).Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer.Objectives:To assess efficacy and safety of CZP in women with uveitis during pregnancy.Methods:Multicenter study of women with uveitis under CZP during pregnancy and their neonates.Results:14 women (23 eyes); mean age 34.3±5.5 yrs (TABLE 1). Pattern of uveitis: 10 anterior, 2 posterior, 1 intermediate, 1 panuveitis. Uveitis was bilateral in 9 and chronic in 7. CZP was started before conception in 10 patients and after in 4. All patients obtained or maintained ocular remission throughout pregnancy (FIGURE). Prednisone was reduced from a mean dose of 21.7±19.7 mg/day to 4.1±3.8 mg/day at 6 months (p=0.03), leading to complete discontinuation in 4. 15 healthy infants were born. Only 1 woman presented a mild infection. No infections or malformations were found in neonates after a follow-up of 6 months. 6 infants were breastfed and all received scheduled vaccinations without complications (TABLE 2).TABLE 1.AgeUnderlying diseaseImmunosuppressants before CZPCombined treatment134SpAMTX, AZA, ADAAZA237SpAMTX, AZA, IFX, ADA, GOLI339SpAAZA, ADAAZA446SpACyA, ETN, ADA, IFX, GOLI532SpASSZ, ADASSZ636SpAMTX, HCQ, ADA740SpAMTX, LFN, HCQ, IFX, ADA, GOLIHCQ831IdiopathicMTX, MMF, CyA, ADA933IdiopathicMTX, AZA, ADA, ETN1032RAMTXAZA1123Vogt-Koyanagi-HaradaAZA, ADAAZA1236Juvenil Idiopathic ArthritisADA1332Punctate inner choroidopathyADA1429BehcetCyA, IFX, ADAConclusion:CZP seems to be effective and safe in female patients with uveitis during pregnancy and neonates.References:[1]Llorenç V et al. Certolizumab Pegol, a New Anti-TNF-α in the Armamentarium against Ocular Inflammation. Ocul Immunol Inflamm. 2016;24(2):167-72. doi: 10.3109/09273948.2014.967779[2]Urruticoechea-Arana A et al. Efficacy and safety of biological therapy compared to synthetic immunomodulatory drugs or placebo in the treatment of Behçet’s disease associated uveitis: a systematic review. Rheumatol Int. 2019 Jan;39(1):47-58. doi: 10.1007/s00296-018-4193-z[3]Martín-Varillas JL et al. Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet’s Disease Ophthalmology. 2018 Sep;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020[4]Santos-Gómez M et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behçet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol. 2016. Sep-Oct;34(6 Suppl 102): S34-S40[5]Calvo-Río V et al. Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients.Semin Arthritis Rheum. 2016 Aug;46(1):95-101. doi: 10.1016/j.semarthrit.2016.03.002Disclosure of Interests:D. Prieto-Peña: None declared, Monica Calderón-Goercke: None declared, Alfredo Adan: None declared, Lillian Chamorro-López: None declared, Olga Maiz: None declared, JR De Dios-Jiménez Aberásturi: None declared, Raul Veroz Gonzalez: None declared, Soledad Blanco: None declared, José M Santos: None declared, Francisco Navarro: None declared, Adela Gallego: None declared, Senen González-Suárez: None declared, Arantxa Conesa: None declared, Andrea García-Valle: None declared, Miguel Cordero-Coma: None declared, Nieves Pardiñas-Barón: None declared, Rosalía Demetrio-Pablo: None declared, Vanesa Calvo-Río Grant/research support from: MSD and Roche, Speakers bureau: AbbVie, Lilly, Celgene, Grünenthal, UCB Pharma, Victor Manuel Mora-Cuesta: None declared, Santos Castañeda: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD

Three cases of patients with decreased visual acuity and papillitis at onset with subsequent macular star development after a few weeks are presented. Complementary tests were unremarkable in all included patients. Based on this clinical context, they were diagnosed with Leber's idiopathic stellate neuroretinitis, were treated with corticosteroids, as well as with antibiotics in 2cases. All patients showed favourable outcomes, although signs of papillary atrophy were observed in the affected eyes. Leber's idiopathic stellate neuroretinitis diagnosis can be challenging due to the wide spectrum of conditions that have to be ruled out. In addition, macular star may appear later on, which should not exclude its diagnosis. Use of antibiotics and/or corticosteroids is controversial considering its benign nature, but should be considered in selected severe cases. Moreover, the routine use of complementary tests should be carefully evaluated, mainly those that can be aggressive and/or expensive, which should be rationally used.

Background Posterior segment uveitis (PSU) is a sight-threatening condition Objectives To perform a systematic review of the literature on the use of immunomodulatory drugs in adult patients with non-infectious and non-malignant PSU including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular oedema (ME). Methods Search strategies were designed for Medline, Embase, and Cochrane Library for articles with clinical, safety or cost-effectivity data up to, Jan 2017 followed by secondary search from their bibliography. Quality was assessed (Jadad/Oxford) Results From 1103 articles, 31 moderate quality clinical trials (CT) were selected, prospective/retrospective, with variability in mean duration, No. and patient’s characteristics. PSU was treated with synthetic DMARDs methotrexate (MTX), azathioprine (AZA), cyclosporine A (CsA), cyclopshosphamide (CyC), tacrolimus, sirolimus, micophenolate (MMF) and interferon β, and biologic DMARDs ranibizumab, daclizumab, rituximab (RTX), secukinumab, adalimumab (ADA), bevacizumab and infliximab (IFX) at usual dosages. Most common measures: visual acuity (VA), macular thickness and vitreous haze. MTX vs.MMF, was effective in IU, PU and PanU, with no differences in efficacy and adverse events (AEs), neither in Vogt-Koyanagi-Harada. MTX was effective with RTX, and SC was inferior to IFNβ with lower rate of AEs in IU with cistoid ME (CME). CsA did not show efficacy vs. placebo (pbo), with more neurological AEs. Tacrolimus vs. CsA was safer with similar efficacy, and CsA was useful with no differences vs. prednisone (pred) or vs.CsG, and similar vs.CYC at 2 y in Behçet PSU. CsA +pred + ketoconazole combined showed additional benefits. CYC+AZA were effective in PU, except for VA and retinal vasculitis, with no differences vs. RTX +MTX. CYC was useful in serpiginoid choroiditis ±dexamethasone. ADA was useful in IU, PU and PanU vs. pbo. IFX in Behçet PSU, was more effective vs. prednisolone +CsA + AZA/MTX. Intravitreal ADA and IFX did not show any benefit. Secukinumab vs. pbo did not prevent recurrences. In another RCT, IV route showed a higher response rate vs.SC for 30 mg/kg, with similar rate of EAs. Intravitreal bevacizumab was effective in multifocal choroiditis and CME. Intravitreal ranibizumab was useful in pigmentary retinitis +CME. Daclizumab in Behçet PSU did not show benefit vs. pbo. Tacrolimus as 2nd line in PU was effective ±pred. Intravitreal and subconjunctival sirolimus were effective in IU, PU and PanU in vitreal haze but not VA and ME, improving functional scores Conclusions 1 Moderate quality of evidence 2 Variability in patients, definitions and outcomes 3 Systemic DMARDs MTX, MMF, CsA, CyC, tacrolimus, sirolimus, MMF and IFNβ were useful in PSU;AZA in combination 4 Biologic DMARDs ADA, IFX (systemic), ranibizumab, bevacizumab (intravitreal) were useful, daclizumab did not show efficacy. Possible efficacy of secukinumab 5 Intravitreal anti-TNF (ADA,IFX) were not useful Disclosure of Interest None declared

Background Uveitis is a severe manifestation of Juvenil Idiopathic Arthritis (JIA). Anti-TNFa are recommended in refractory cases, mainly infliximab (IFX) or adalimumab (ADA) (Levy-Clarke et al. Ophthalmology 2014; 121: 785–796). However, sometimes they are ineffective, contraindicated or not tolerated. The next therapeutic step is not defined. Objectives To compare the efficacy of Golimumab (GLM) and Tocilizumab (TCZ) in related AIJ uveitis refractory to conventional immunosuppressive drugs and anti-TNFα. Methods Multicenter study of 33 patients with uveitis associated-JIA. They were refractory to conventional treatment with high dose of corticosteroids and at least a) one conventional immunosuppressive drug and b) one anti-TNFa. For this reason it was decided to iniciate TCZ or GLM. TCZ was used in 25 patients: 8 mg/kg/4 w iv (n=21), 8 mg/kg/2 w (n=2); 8 mg/kg/8 w (n=1) and 2.9 mg/kg sc/w (n=1). GLM was used in 8 patients (50 mg/sc/month). We assessed visual acuity (VA), degree of intraocular inflammation, vitreous inflammation and macular thickening (with OCT). Quantitative variables were expressed with mean±SD or median [IQR], according to its distribution. They were compared with the Student t or the Mann-Whitney U test, respectively. Dichotomous variables were expressed as percentages and compared by the chi-square test. Results We studied 33 patients/61 affected eyes. There were no significant differences between TCZ and GLM at baseline in sex (♂/♀;4/21 vs 3/5; p=0.19), mean age (18.5±8.3 vs 19.9±8.7; p=0.55), positive ANA (95% vs 100%; p=0.7), uveitis duration before TCZ or GLM onset (116.4±93.6 vs 142.3±74.7 p=0.46), number of previous biological treatments (1.9±1.1 vs 2±1.4; p=0.84), VA (0.57±0.35 vs 0.5±0.37; p=0.42), combined immunosuppressive therapy (88% vs 75%; p=0.37), presence of cells in the anterior chamber (median, 1 [0–1] vs 1 [0.25–1.5]; p=0.6), vitritis (0 [0–0] vs 0 [0–1]; p=0.7), macular thickening (358.7±92.2 vs 313.6±77.1; p=0.32). There were no significant difference in the efficacy between TCZ and GLM (TABLE). After a mean follow-up of 20.48±11.7 months with TCZ and 24.25±17 months with GLM the following side effects were observed: TCZ: viral conjunctivitis plus bullous impetigo (n=1), severe thrombocytopenia and pneumonia. This last patient showed hemolytic anemia, thrombocytopenia and splenomegaly, for this reason treatment with TCZ was discontinued. With GLM cutaneous reaction was observed in 2 patients. Conclusions TCZ and GLM seem to be equally effective and safe for refractory uveitis associated-JIA. The superiority of one or the other should be established with prospective randomized studies “Head to Head” Disclosure of Interest None declared

Objectives To evaluate the efficacy of adalimumab (ADA) in short and long term follow-up in refractory uveitis of Behçet9s disease (BD) Methods Multicenter study. Ocular inflammation was evaluated according to “SUN working Group” (Am J Ophthalmol 2005;140:509–516), and the macular thickening with OCT. A comparison was carried out between baseline, and follow-up visits. Results are expressed as mean±SD or median [IQR]. Continuous variables were compared with Wilcoxon test. Results We studied 74 patients/132 affected eyes (39M/35W); mean age 38.7±11.3. The ocular pattern was panuveitis (n=45), posterior uveitis (n=14), anterior uveitis (n=14) and intermediate uveitis (n=1). Before ADA, systemic treatment with corticosteroids, iv metilprednisolone (n=23), Cyclosporin A (58), azathioprine (33), metotrexate (31) and other drugs (28) was used. The dose of ADA was 40 mg/2 weeks/ sc in monotherapy (n=22) or combined (n=52). Most patients showed a rapid and progressive improvement (TABLE). The 24 patients (37 affected eyes) with CME showed a significant improvement. ADA was optimized in 23 (31.1%) that were in remission for 15.3±9 months. Interval of administration was increased to 3 (n=6), 4 (13), 5 (1), 6 (1) and 8 weeks. After a mean follow-up of 13.0±9.7 months after optimization, 21 patients were stable and 2 had a severe flare. In 4 patients ADA was stopped after 35.2±9.3 months in remission. The main adverse effects observed were lymphoma (n=1), pneumonia (1), and 2° bacteriemia by E. Coli (1) Conclusions ADA was effective in short and long-term follow-up in refractory uveitis associated to BD. Optimization or even suspension of ADA is possible. Disclosure of Interest None declared

CLINICAL CASE:We report the case of a 45-year-old woman, with unremarkable past medical history, who presented with acute visual loss in her left eye due to bilateral posterior uveitis. After the screening, she was diagnosed with acute syphilitic placoid chorioretinitis and was treated with intravenous penicillin.DISCUSSION:Clinical manifestations of ocular syphilis are extremely heterogeneous and may mimic several aetiologies. Anti-treponema treatment usually induces a quick and positive response in affected patients. Prompt and proper diagnosis of these patients is crucial, although anatomical and functional damage may persist.

Background In non-infectious no anterior uveitis, adalimumab (ADA) is the only biologic that has shown efficacy in phase III randomized, double blind studies, such as VISUAL I and VISUAL II. (Brezin AP et al Arthritis Rheumatol 2015;67 (suppl 10): 2038 & Nguyen QD et al Arthritis Rheumatol 2015; 67 (suppl 10): 1388). After a 80 mg loading dose, maintenance dose is the standard for other indications, 40 mg/sc/2 weeks. Objectives Our objective is to test a series of Behcet9s síndrome uveítis, and proving if once remission was obtained, it was posible to “optimize” the maintenance dose. Methods Multicenter study of 174 patients with Behcet9s síndrome refractory uveitis. All of them had insufficient response or intolerance to conventional treatment with corticosteroids and at least 1 systemic immunosuppressive drug. 71 patients started treatment with ADA and once remission was achieved, it was optimized in 23 of them. The degree of ocular inflammation was assessed by “the Standardization of Uveitis Nomenclature (SUN) Working Group” (Am J Ophthalmol 2005; 140: 509–516), and macular thickness by optical coherence tomography (OCT). A comparison was made between the first visit before initializing ADA at standard dose, the start of the optimization of the drug, and the final visit. The results are expressed as mean ± 1 SD for variables with a normal distribution, and as median [IQR 25–75] (range) when it is not normal. Comparison of continuous variables was performed using the Wilcoxon test. Results 23 patients/42 affected eyes (15 men/8 women) who had a dose optimization were studied, the median age was 37.2 ± 13.4 years (range 10–62). HLA-B51 was positive in 60.8%. Prior to ADA, and as systemic treatment besides oral steroids, they had received intravenous methylprednisolone bolus (n=7), cyclosporin A (CyA) (n=20), methotrexate (MTX) (n=11) and azathioprine (AZA) (n=11). ADA monotherapy was used in 5 cases and also in combination with immunosuppressants: CyA (n=12), MTX (n=4) and AZA (n=2). The average remission before optimization of the dose was 15.3 ± 9 months. In 23 patients the interval dose of adalimumab was progressively increased to 3 weeks (n=6), 4 weeks (n=13), 5 weeks (n=1), 6 weeks (n=1) and 8 weeks (n=2). Only 2 patients had to return to the standard dose of ADA due to serious outbreak after optimizing the drug, reaching again remission of uveitis. It was also posible to suspend ADA in 4 patients after 35.2 ± 9.3 months in remission, not presenting a new outbreak after a mean of 20 ± 6.9 months following the suspension. There were not serious side effects during a mean follow-up of 34.7 ± 13.3 months after starting ADA. Conclusions Optimizing ADA therapy, once remission is achieved, seems feasible in Behcet9s síndrome uveítis refractory to systemic treatment. Disclosure of Interest None declared

Objectives To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Methods Multicenter study of SpA-related uveitis refractory to at least one immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. Results Fifteen patients (13 men/2 women; 18 affected eyes; mean age 39±6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n=8), psoriatic arthritis (n=6) and non-radiographic axial SpA (n=1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n=13), sulfasalazine (n=6), pulses of methylprednisolone (n=4), azathioprine (n=3), leflunomide (n=2) and cyclosporine (n=1). Ten of them had also been treated with TNF-α blockers; etanercept (n=7), adalimumab (n=7), infliximab (n=6), and certolizumab (n=1). GLM was given at the standard dose (50 mg/sc/monthly) as monotherapy (n=7) or in combination with conventional immunosuppressive drugs (n=8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years (0 [0–0]) was significantly reduced compared to baseline findings (1 [0–3]); p=0.04). The mean best corrected visual acuity value also improved (0.84±0.3 at 2 years versus 0.62±0.3 at baseline; p=0.03). Only minor side effects were observed after a mean follow-up of 23±7 months. Conclusions Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis. Disclosure of Interest None declared

Presentamos el caso de una mujer de 45 años sin antecedentes de interés y con una pérdida súbita de visión en su ojo izquierdo secundaria a una uveítis posterior bilateral. Tras despistaje, se diagnosticó de coriorretinitis placoide posterior aguda sifilítica, y recibió tratamiento con penicilina intravenosa. Existen múltiples manifestaciones oculares de la sífilis que pueden simular cuadros y etiologías muy diversas. El tratamiento anti-treponémico normalmente produce una rápida y positiva respuesta en pacientes afectos. El diagnóstico precoz y certero de estos pacientes es por tanto crucial aunque, en ocasiones, los daños anatómicos y funcionales son irreversibles. We report the case of a 45-year-old woman, with unremarkable past medical history, who presented with acute visual loss in her left eye due to bilateral posterior uveitis. After the screening, she was diagnosed with acute syphilitic placoid chorioretinitis and was treated with intravenous penicillin. Clinical manifestations of ocular syphilis are extremely heterogeneous and may mimic several aetiologies. Anti-treponema treatment usually induces a quick and positive response in affected patients. Prompt and proper diagnosis of these patients is crucial, although anatomical and functional damage may persist.

CASE REPORT:We report the case of an immunocompetent male who presented with a limbal-adjacent scleritis and interstitial keratitis in the left eye. A few days later a new dendritiform ulcer in his right eye and bilateral progressive worsening with granulomatous uveitis in both eyes were observed. A thorough review of systems revealed positive serum IgM titles for herpes simplex virus.DISCUSSION:In the context of a bilateral keratouveitis refractory to conventional treatment it is mandatory to rule out the herpetic origin based on the different forms of clinical presentation of this virus.

Background Classic management of uveitis due to Behçet9s disease (UBD) consists of conventional immunosuppressive drugs. However, UBD is often refractory requiring more intensive therapy. Objectives To assess long-term response in UBD patients refractory to conventional therapy. Methods Multicenter study of 165 patients with UBD followed-up in the uveitis units of 45 hospitals. All of them had inadequate response or intolerance to traditional treatment with corticosteroids and at least 1 systemic immunosuppressive drug. The degree of ocular inflammation was assessed as “the Standardization of Uveitis Nomenclature (SUN) working Group” (Am J Ophthalmol 2005; 140: 509-516), and macular thickness was assessed by optical coherence tomography (OCT). Comparisons were made between baseline and the 1st week, 2nd week, 1st month, 6th month, 1st, 2nd, 3rd,4th and 5th year. Results 165 patients (89 men/76 women/297 affected eyes) with a mean age of 39.3±10.5 years (range 10-67) were studied. HLA-B51 was positive in 64.8%. Prior to biologic therapy and in addition to oral corticosteroids, patients had received the following drugs: Intravenous pulses of methylprednisolone (50 patients), cyclosporine A (CyA) (134), methotrexate (MTX) (72) and azathioprine (AZA) (87). Infliximab (IFX) was the first biologic used in 96 cases (58.2%) and adalimumab (ADA) in the remaining 69 (41.8%) patients. These agents were used as a monotherapy in 46 cases or in combination with immunosuppressive drugs: CsA (58 cases), MTX (34), AZA (24), mycophenolate (1), cyclophosphamide (1) and tacrolimus (1). The most common regimens were IFX 5 mg/kg/i.v. every 4-8 weeks and ADA 40 mg sc/2 weeks. In the course of the diseases, in cases of refractory uveitis to these drugs switching to other biologic agents was performed: golimumab (n=6), tocilizumab (5), rituximab (2), certolizumab (1) and etanercept (1). Nevertheless, in 30 cases the biologic agents were discontinued because of maintained clinical remission. Significant improvement observed since the 1sr week was observed in the visual acuity (VA), Tyndall and vitritis. OCT improvement was observed since the 2nd week (TABLE). At baseline, 57 patients (95 eyes) had macular thickening (OCT>250μ) and 33 patients (50 eyes) had cystoid macular edema (CME) (OCT>300μ). The OCT improved from 344.5±137.3 microns to 254.2±60.8 microns (p<0.01). After a mean follow-up of 38.3±22.4 months the most serious side effects were miliary TB (n=1), Mycobacterium avium pneumonia (n=1), melanoma (n=1), and fatal lymphoma (n=1). Conclusions Biological treatment with IFX or ADA are effective and relatively safe in UBD refractory to conventional therapy. Disclosure of Interest None declared

Se presenta el caso de un varón inmunocompetente que acude a nuestro servicio con escleritis adyacente a limbo y queratitis intersticial en ojo izquierdo. A los pocos días se observa nueva úlcera de aspecto dendritiforme en ojo derecho y empeoramiento bilateral progresivo hasta presentar uveítis granulomatosa en ambos ojos. En el estudio etiológico destacan títulos positivos de IgM para virus herpes simple en suero. Ante un cuadro de queratouveítis bilateral de tórpida evolución con tratamiento convencional, es necesario descartar el origen herpético debido a las diferentes presentaciones de este virus. We report the case of an immunocompetent male who presented with a limbal-adjacent scleritis and interstitial keratitis in the left eye. A few days later a new dendritiform ulcer in his right eye and bilateral progressive worsening with granulomatous uveitis in both eyes were observed. A thorough review of systems revealed positive serum IgM titles for herpes simplex virus. In the context of a bilateral keratouveitis refractory to conventional treatment it is mandatory to rule out the herpetic origin based on the different forms of clinical presentation of this virus.