Marina Mesquida

Dexamethasone intravitreal implant for treatment of uveitic persistent cystoid macular edema in vitrectomized patients.

Purpose: To evaluate the safety and efficacy of Ozurdex (dexamethasone intravitreal implant) 0.7 mg in the treatment of uveitic macular edema in vitrectomized eyes. Methods: Data from 13 patients (17 eyes) with persistent uveitic cystoid macular edema and a history of pars plana vitrectomy in the study eyes that were treated with intravitreal injection of 0.7-mg dexamethasone implant were reviewed retrospectively. Main outcome measures were changes in central retinal thickness measured by optical coherence tomography and changes in best-corrected visual acuity. Results: The median age of patients was 61 years (range, 19–81 years). The median duration of uveitic macular edema was 12 months (range, 2–72 months). The mean baseline central retinal thickness (95% confidence interval) was 461.6 &mgr;m (403.8–519.4), decreased to 277.2 &mgr;m (244.6–309.8) at 4 weeks (P < 0.01), remained low at 349.9 &mgr;m (281.8–418.0) at 3 months (P = 0.01), and then reached 394.1 &mgr;m (328.3–459.8) at 6 months (P = 0.14). After 3 months, there was a median improvement of 2 lines of best-corrected visual acuity, with 52.9% of eyes gaining 2 lines or more (P < 0.01). At 6 months, there were 5 eyes that maintained the 2 lines gain and none had lost >1 line from baseline (P = 0.03). In 8 eyes (47.1%), reinjection of the implant was performed at a mean of 6.5 months. Ocular hypertension (47.1%), hypotony (11.8%), anterior chamber displacement of the implant (5.9%), and glaucoma, which required filtration surgery (5.9%), were the most common adverse events. Mean follow-up was 9.6 months (range, 6–17 months). Conclusion: In this small case series of eyes with limited follow-up, treatment with dexamethasone intravitreal implant injection for uveitic macular edema in vitrectomized eyes was associated with favorable visual outcomes and had an acceptable safety profile.

Anti-TNF-α therapy in patients with refractory uveitis due to Behçet’s disease: a 1-year follow-up study of 124 patients

OBJECTIVE The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçets disease (BD). METHODS We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. RESULTS Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 μm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 μm) that improved from 420 μm (s.d. 119.5) at baseline to 271 μm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. CONCLUSION Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.

Epidemiology of uveitis in a Western urban multiethnic population. The challenge of globalization

To report the anatomical pattern and etiological spectrum of uveitis in an urban multi‐ethnic population from Barcelona, Spain. General and specific epidemiological data for the most prevalent aetiologies are also calculated.

Behçet Disease-associated Uveitis Successfully Treated with Golimumab

Abstract Over the past decade, the off-label use of biologic agents such as TNF-α antagonists, including infliximab and adalimumab, has improved the treatment armamentarium for refractory immune-mediated uveitis, with particular success in Behçet disease-associated uveitis. Golimumab is a novel fully human anti-TNF-α monoclonal antibody that has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, with very promising results. Herein, the authors present the use of GLM in a case of Behçet uveitis refractory to other TNF-α blockers. There are only two reports in the literature about the use of GLM in uveitis, describing four patients with JIA-associated uveitis and a case of idiopathic retinal vasculitis. To the authors’ knowledge, this is the first report about the use of GLM in Behçet uveitis.

Long-Term Effects of Tocilizumab Therapy for Refractory Uveitis-Related Macular Edema

OBJECTIVE To report the long-term efficacy and safety of the interleukin-6 receptor antagonist tocilizumab for refractory uveitis-related macular edema (ME). DESIGN Retrospective cohort study. PARTICIPANTS Eyes with uveitis seen at a single tertiary referral center for which ME was the principal cause of reduced visual acuity. METHODS Data were obtained by standardized chart review. MAIN OUTCOME MEASURES Central foveal thickness (CFT) measured by optical coherence tomography, degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), and visual acuity (logarithm of the minimum angle of resolution [logMAR]) were recorded during tocilizumab therapy at months 1, 3, 6, and 12. RESULTS Eleven eyes from 7 patients (all women) were included. Mean age was 43.4 years. Mean duration of ME was 14.2 years. Mean follow-up with tocilizumab therapy was 15.2 months (range, 12-18 months). Before tocilizumab therapy, conventional immunosuppressive therapy and 1 or more biologic agents failed in all patients. Uveitis diagnoses were birdshot chorioretinopathy (n = 3), juvenile idiopathic arthritis-associated uveitis (n = 3), and idiopathic panuveitis (n = 1). Mean CFT was 550 ± 226 μm at baseline, 389 ± 112 μm at month 1 (P = 0.007), 317 ± 88 μm at month 3 (P = 0.01), 292 ± 79 μm at month 6 (P = 0.006), and 274 ± 56 μm at month 12 of follow-up (P = 0.002). Mean logMAR best-corrected visual acuity improved from 0.67 ± 0.53 at baseline to 0.4 ± 0.56 at month 12 (P = 0.008). Tocilizumab therapy was withdrawn in 2 patients because of sustained remission at month 12. In both patients, ME relapsed 3 months after tocilizumab withdrawal. Reinitiation of tocilizumab therapy led to good uveitis control and ME resolution. Tocilizumab generally was well tolerated and no serious adverse events were reported. CONCLUSIONS In this study, tocilizumab was effective in the treatment of refractory inflammatory ME. No serious adverse events were observed.

Interleukin‐6 blockade in ocular inflammatory diseases

Interleukin‐6 (IL‐6) is a key cytokine featuring redundancy and pleiotropic activity. It plays a central role in host defence against environmental stress such as infection and injury. Dysregulated, persistent interleukin (IL)‐6 production has been implicated in the development of various autoimmune, chronic inflammatory diseases and even cancers. Significant elevation of IL‐6 has been found in ocular fluids derived from refractory/chronic uveitis patients. In experimental autoimmune uveitis models with IL‐6 knock‐out mice, IL‐6 has shown to be essential for inducing inflammation. IL‐6 blockade can suppress acute T helper type 17 (Th17) responses via its differentiation and, importantly, can ameliorate chronic inflammation. Tocilizumab, a recombinant humanized anti‐IL‐6 receptor antibody, has been shown to be effective in several autoimmune diseases, including uveitis. Herein, we discuss the basic biology of IL‐6 and its role in development of autoimmune conditions, focusing particularly on non‐infectious uveitis. It also provides an overview of efficacy and safety of tocilizumab therapy for ocular inflammatory diseases.

Anti-TNF-α therapy in refractory uveitis associated with sarcoidosis: Multicenter study of 17 patients

OBJECTIVES To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. METHODS Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. RESULTS A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF-α therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load. CONCLUSION Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.

Golimumab as Rescue Therapy for Refractory Immune-Mediated Uveitis: A Three-Center Experience

Objective. To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM) for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. Methods. Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks) during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. Results. Eight men and 5 women (22 affected eyes) with a median age of 30 years (range 20–38) and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%). GLM therapy achieved complete control of inflammation in 12/13 patients (92.3%) after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P = 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 μ, P = 0.05) at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. Conclusions. GLM is a new and promising therapeutic option for patients with severe and refractory uveitis.

Indirect supportive evidence for diagnosis of tuberculosis-related uveitis: from the tuberculin skin test to the new interferon gamma release assays.

Purpose:  To evaluate clinical and paraclinical parameters for the indirect diagnosis of tuberculosis‐related uveitis (TRU).

Anti–Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis–Associated Uveitis Refractory to Anti–Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients

To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)–associated uveitis.