Blanca Molins

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.

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.

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.

Long-term evaluation of dexamethasone intravitreal implant in vitrectomized and non-vitrectomized eyes with macular edema secondary to non-infectious uveitis

PurposeTo compare dexamethasone (DEX) intravitreal implant effect in non-vitrectomized (non-PPV) vs vitrectomized (PPV) eyes with macular edema (ME) secondary to non-infectious uveitis.MethodsMedical records of patients with uveitic ME treated with DEX-intravitreal implant were reviewed. Main outcome measures were changes in central retinal thickness (CRT), best corrected visual acuity (BCVA), intraocular pressure (IOP), vitreous haze and adverse events. Statistical analysis was performed by Longitudinal Linear model using the General Estimating Equation methodology.ResultsForty-two eyes of 32 patients were included. Median follow-up time was 18 months (interquartile range (IQR): 12–24). Median CRT showed its maximum decrease at the first month in non-PPV and PPV eyes without statistically significant differences between both groups (P=NS). Median Snellen BCVA, converted to logarithm (LogMAR), showed its maximum improvement at third month in both groups without statistically significant differences between them (P=NS). Median IOP was higher in non-PPV eyes than in PPV eyes from third (P=0.025) to 12th month (P=0.013). Vitreous haze score improved in both groups since first month and showed no differences (P=0.706). Reinjection was performed in 45.2% of eyes at a median time of 5 months IQR: (5–6). Ocular hypertension (47.6%) was the most common adverse event.ConclusionsDEX-intravitreal implant for uveitic ME has similar long-term safety profile and good response measured in terms of CRT decrease, BCVA, and vitreous haze improvement in both groups. Non-PPV eyes following DEX-intravitreal implant showed higher IOP increase than PPV eyes, showing the need for close IOP monitoring.

Proinflammatory Cytokines and C-Reactive Protein in Uveitis Associated with Behçet’s Disease

The aim of the present study was to determine the serum cytokine profile and levels of high sensitivity C-reactive protein (hsCRP) in patients with uveitis associated with Behçets disease (BD) and to compare them with those obtained from healthy control subjects. We determined the serum concentration of interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-12p70, IL-17A, tumor necrosis factor-α (TNF-α), and hsCRP in 13 patients with active uveitis associated to BD, 24 inactive BD patients, and 20 controls. In a subgroup of 10 active patients, a second serum sample was obtained when the disease was inactive. Cytokine profiles and hsCRP levels were correlated with disease activity, severity, complications, and visual outcome. Levels of IFN-γ and TNF-α were significantly increased in patients with active uveitis associated to BD compared to controls (P < 0.05). IFN-γ, TNF-α, and hsCRP were significantly higher during active uveitis associated to BD compared to inactive disease (P < 0.05). Furthermore, IL-17A was significantly increased in patients with active BD without pharmacological treatment compared to controls (P < 0.05). No significant correlations were found with specific cytokine profiles and disease severity, visual outcome, or complications. In summary, increased serum levels of IFN-γ, TNF-α, IL-17A, and hsCRP were associated with active uveitis associated with BD and might serve as markers of disease activity.

Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

The aim of this study was to quantify the proportion of regulatory T cells (Treg) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non‐infectious uveitis, and to evaluate the effect of in‐vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non‐infectious uveitis and 18 age‐matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)+ Treg cells and intracellular tumour necrosis factor (TNF)‐α expression in CD4+ T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti‐CD3/anti‐CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF‐α, interleukin (IL)‐10, IL‐17 and interferon (IFN)‐γ levels were measured by enzyme‐linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF‐α and lower amounts of IL‐10. Dexamethasone treatment in vitro significantly reduced FoxP3+ Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF‐α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL‐17 and IFN‐γ production in PBMCs and dexamethasone up‐regulated IL‐10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF‐α and less IL‐10 than healthy subjects, and this is independent of FoxP3+ Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3+ Treg cells.

Clinical pattern of toxoplasmic retinochoroiditis in a Spanish referral center.

Background/Aims: To analyze the clinical pattern of ocular toxoplasmosis in a referral center in Spain. Methods: The medical records of consecutive patients with ocular toxoplasmosis admitted from a single referral center for uveitis in Barcelona (Spain) were retrospectively analyzed between January 2005 and January 2011. Results: One hundred and thirteen eyes from 113 patients (74 Spanish and 39 South American) with active ocular toxoplasmosis were analyzed with a 12-month follow-up. Final BCVA ≤20/200 was found in 30 eyes (26.5%). The most frequent complications were macular edema (16.8%) and epiretinal membrane (11.5%). Anterior chamber cell scores of ≥2+ (p = 0.003), vitreous cell scores of ≥2+ (p = 0.001), and the presence of cataracts (p = 0.047) or serous retinal detachment (p = 0.008) were more common among the South American than Spanish cohort. Active macular lesions (p < 0.001) with an initial BCVA ≤20/200 (p < 0.001) and advanced age (p = 0.019) were predictors for final BCVA ≤20/200, whereas female gender (p = 0.021) and an initial BCVA ≤20/200 (p = 0.045) were predictors for ocular complications. Moreover, a BCVA ≤20/200 (p < 0.001) and a vitreous cell score of ≥2+ (p = 0.045) at the initial examination were predictors of an eventual need for ocular surgery. Conclusion: The clinical features of ocular toxoplasmosis in Spanish patients differ from those of South American patients. In general, active macular lesions with an initial BCVA ≤20/200 and advanced age were shown to be predictors for final BCVA ≤20/200 in our patient cohort.

Elevated Serum Immune Mediators and Subclinical Inflammation in HLA-A29-associated Birdshot Chorioretinopathy

ABSTRACT Purpose: To determine the circulating levels of seven immune mediators in serum samples from patients with birdshot chorioretinopathy (BSCR). Methods: A single-center prospective case–control study was performed. Serum concentrations of IFN-γ, IL-12p70, IL-1β, IL-17A, IL-23, TNF-α, and TGF-β1 of 22 BSCR patients recruited at Hosp6ital Clinic of Barcelona and 16 healthy subjects were determined. Results: Circulating levels of IL-17A were elevated in patients with BSCR in remission (p = 0.008 for BSCR patients with immunomodulatory treatment [IMT] and p = 0.032 for patients without IMT) compared with healthy subjects. Furthermore, patients who were not receiving IMT had significantly higher levels of circulating IL-23 (p = 0.013 vs controls and p = 0.001 vs IMT) and TGF-β1 (p = 0.009 vs controls and p = 0.001 vs IMT) than patients under IMT or healthy subjects. Conclusions: Our results support the involvement of a IL-17-response in BSCR and suggest that BSCR patients without IMT due to apparent remission may maintain a subclinical inflammatory background.

Cytokine profiling reveals decreased serum levels of CCL2 in active ocular toxoplasmosis

Background Toxoplasma gondii infection is an important cause of ocular disease. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immunocompetent individuals. The purpose of the current investigation was to study the cytokine profiles in serum from patients with ocular toxoplasmosis and to compare them with those obtained from healthy control subjects. Methods Using a multiplex assay, we determined the serum concentration of granulocyte colony-stimulating factor (GCSF), interferon γ (IFNγ), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, chemokine (C-C motif) ligand 2 (CCL2) and tumour necrosis factor α (TNFα) in patients with inactive ocular toxoplasmosis (n=48), active ocular toxoplasmosis (n=21), and an age-matched and sex-matched healthy control group (n=25). In a subgroup of 17 patients with active disease, a second serum sample was obtained when the disease was inactive. Cytokine profiles were correlated with disease activity, severity and visual outcome. Results Levels of CCL2 were significantly reduced in patients with active ocular toxoplasmosis compared to the control group (564±42 pg/mL vs 455±35 pg/mL, p<0.05). Moreover, CCL2 levels were significantly lower during active ocular toxoplasmosis compared to inactive disease (569±32 pg/mL vs 433±32 pg/mL, p<0.01). GCSF and TNFα were elevated in patients with toxoplasmosis with poor visual outcome. No significant correlations were found with specific cytokine profiles and disease severity. Conclusions Decreased serum levels of CCL2 may be associated with active ocular toxoplasmosis and could therefore serve as a marker of disease activity.

Twenty-four Month Follow-up Of Tocilizumab Therapy For Refractory Uveitis-related Macular Edema

Background: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). Methods: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. Outcome Measures: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24. Results: Sixteen eyes from 12 patients (10 women) were included. Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients achieved 24 months of follow-up and that is the census date for data collection. Before TCZ was commenced, ME was present, and all patients had been previously treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia (n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%; confidence interval) was 516 ± 55 &mgr;m at baseline, improving to 274 ± 13 at Month 12 (P = 0.0004), and sustained at 274 ± 14 at Month 24 of follow-up (P = 0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.78 ± 0.18 (Snellen 20/120 ± 20/30) at baseline to 0.42 ± 0.17 (20/52 ± 20/30) at Month 12 (P = 0.0001) and 0.40 ± 0.17 (20/50 ± 20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn in 5 patients with sustained remission at Month 12 but in all, ME relapsed between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions led to recovery of uveitis control and ME resolution. Two adverse events were reported during two 4-month follow-ups: one Grade 1 neutropenia and one community-acquired pneumonia. Conclusion: In this long-term study, TCZ was effective and had a comparable safety profile to published data for TCZ use in other indications, when used for the treatment of refractory uveitis-related ME.