David Salom

Treatment of Refractory Uveitis with Adalimumab: A Prospective Multicenter Study of 131 Patients

OBJECTIVE To evaluate adalimumab therapy in refractory uveitis. DESIGN Prospective case series. PARTICIPANTS A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated. INTERVENTION Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). MAIN OUTCOME MEASURES Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (optical coherence tomography). RESULTS There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçets disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (P < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] vs 5.40 [4.43]; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses during the 6 months of follow-up. CONCLUSIONS Adalimumab seems to be well tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Further controlled studies of adalimumab for uveitis are warranted.

Adalimumab Therapy for Refractory Uveitis: A Pilot Study

PURPOSE The aim of this study was to assess the efficacy and safety of adalimumab in treating refractory autoimmune uveitis. METHODS This work was a prospective, noncomparative, nonrandomized, clinical trial. Nineteen (19) patients meeting eligibility criteria received a 40-mg subcutaneous (s.c.) injection of adalimumab every other week during 1 year. RESULTS All patients underwent an outcome assessment at month 12. Visual acuity improved by -0.3 logMar in 12 (31%) eyes of 38, and worsened by +0.3 logMar in 1 (2.6%) eye. All patients had an active intraocular inflammation at baseline, and 12 patients (63%) achieved control of their inflammation with adalimumab at the end of follow-up. After optic coherence tomography, 33 eyes (86%) had cystoid macular edema (CME) at baseline, and at the end of follow-up there was a complete resolution of CME in 18 of these 33 eyes (54.54%). All patients were able to reduce at least 50% of the dose of the concomitant immunosuppressive drugs at the end of follow-up. Adalimumab was well tolerated in all patients, and only local minor side effects at the s.c. injection site were observed. Nevertheless, 8 patients (42.10%) had relapses during the follow-up period that were controlled with 1 periocular steroid injection. CONCLUSIONS Adalimumab seems to be an effective, safe therapy for the management of refractory uveitis and may provide the possibility to reduce the concomitant immunosuppressive drugs in these patients. Further long-term studies are warranted to determine the safety and efficacy of adalimumab in treating intraocular inflammation.

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.

Golimumab for uveitis.

Dear Editor: The off-label use of biological response modifiers for the treatment of clinically relevant uveitides has widely increased over the past years. Anti-tumor necrosis factor alpha (TNF) drugs have shown a remarkable efficacy when prescribed for those uveitides associated with select immune-mediated diseases such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), plaque psoriasis, ankylosing spondylitis (AS), Crohn’s disease, and ulcerative colitis. Golimumab (GLM), a fully human anti-TNF monoclonal antibody, was approved by the US Food and Drug Administration in 2009 for the use with methotrexate (MTX) in adults with moderate to severe active RA, and with or without MTX or other biologic disease-modifying anti-rheumatic drugs in adults with active PsA or active AS. Subcutaneous injection of GLM is administered 50-mg once a month. We report 2 cases of uveitis refractory to other anti-TNF agents who favorably responded to GLM.

Fusarium Keratitis 3 Weeks After Healed Corneal Cross-Linking

PURPOSE To report a case of Fusarium solani keratitis after corneal cross-linking (CXL) treatment. METHODS A 23-year-old woman presented with corneal ulcer 4 weeks following a CXL procedure. RESULTS Microbiological studies revealed Fusarium species as the etiological pathogen. CONCLUSIONS Fusarium species may cause infectious crystalline keratopathy after corneal CXL treatment.

INTRAVITREAL PLASMIN WITHOUT ASSOCIATED VITRECTOMY AS A TREATMENT FOR REFRACTORY DIABETIC MACULAR EDEMA

OBJECTIVE To determine the effectiveness of a low-dose intravitreal injection of autologous plasmin enzyme (APE), without the performance of a vitrectomy, as a treatment for refractory diffuse diabetic macular edema (DDME). DESIGN Prospective, comparative, interventional case series. PATIENTS Sixteen patients with bilateral DDME who had not responded to prior laser photocoagulation. All patients received an injection in 1 eye, while the other eye served as a control. INTERVENTION Intravitreal 0.2 mL APE injection under topical anesthesia. The APE was obtained using a simplified method. MAIN OUTCOME MEASURES Central macular thickness (CMT) at 1 and 6 months, determined by optical coherence tomography (OCT) and best corrected visual acuity (BCVA). RESULTS All patients underwent a 1-month follow-up. Prior to injection, CMT in the eye about to receive the injection was 541 +/- 79 microm (mean +/- standard deviation [SD]) versus 535 +/- 76 microm in the control eye. One month after injection, CMT was 241 +/- 47 microm in injected eyes and 530 +/- 85 microm in control eyes (P < 0.001, bilateral Wilcoxon test for paired samples). The macular edema (ME) improved in all injected eyes (100%), with complete resolution in 7 patients (44%). The mean BCVA of treated eyes was 0.618 +/- 0.27 (mean +/- SD) at baseline and 0.45 +/- 0.24 four weeks after injection (paired samples t-test, P < 0.001). No adverse effects were observed in any of the patients. BCVA and CMT were stable when evaluated at 6-month follow-up (0.43 +/- 0.242 and 244 +/- 46 microm, respectively). CONCLUSIONS Intravitreal APE injection effectively reduces macular thickening due to DDME in cases that fail to respond to conventional laser photocoagulation, and improves visual acuity in a short term, and this results remain stable in a medium term what is very important. Further investigation is warranted in order to assess long-term efficacy and safety.

Altered Antioxidant-Oxidant Status in the Aqueous Humor and Peripheral Blood of Patients with Retinitis Pigmentosa

Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular oxidative stress-related disease. Multivariate analysis of covariance revealed that retinitis pigmentosa alters ocular antioxidant defence machinery and the redox status in blood. Patients with retinitis pigmentosa present low total antioxidant capacity including reduced SOD3 activity and protein concentration in aqueous humor. Patients also show reduced SOD3 activity, increased TBARS formation and upregulation of the nitric oxide/cyclic GMP pathway in peripheral blood. Together these findings confirmed the hypothesis that patients with retinitis pigmentosa present reduced ocular antioxidant status. Moreover, these patients show changes in some oxidative-nitrosative markers in the peripheral blood. Further studies are needed to clarify the relationship between these peripheral markers and retinitis pigmentosa.

Short-term results of a single intravitreal bevacizumab (avastin) injection versus a single intravitreal triamcinolone acetonide (kenacort) injection for the management of refractory noninfectious uveitic cystoid macular edema

Purpose: To report the short-term results of a single intravitreal injection of bevacizumab (IVB) versus a single intravitreal injection of triamcinolone acetonide (IVT) to treat refractory noninfectious uveitic cystoid macular edema (CME). Methods: Twenty-eight consecutive patients (36 eyes) were retrospectively included. Patients received either 2.5 mg of IVB (16 eyes) or 4 mg of IVT (20 eyes). Results: In the IVT group, baseline best-corrected visual acuity (BCVA) was logMAR 1.1 ± 0.2, and improved to 0.7 ± 0.3 (p < .001) at 6 months. In the IVB group, baseline BCVA was logMAR of 1.2 ± 0.4 and improved to 0.8 ± 0.4 at 6 months (p = .031). At 6 months, central macular thickness (CMT) in the IVT group improved from 454.8 ± 238.9 μm to 296 ± 134.4 μm (p < .0001). Conclusion: A single IVT injection improves BCVA and reduces CMT more effectively than IVB in refractory noninfectious uveitic CME at 6 months.

Usefulness of Adalimumab in the Treatment of Refractory Uveitis Associated with Juvenile Idiopathic Arthritis

Purpose. To assess the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA) and associated refractory uveitis. Design. Multicenter, prospective case series. Methods. Thirty-nine patients (mean [SD] age of 11.5 [7.9] years) with JIA-associated uveitis who were either not responsive to standard immunosuppressive therapy or intolerant to it were enrolled. Patients aged 13–17 years were treated with 40 mg of adalimumab every other week for 6 months and those aged 4–12 years received 24 mg/m2 body surface. Results. Inflammation of the anterior chamber (2.02 [1.16] versus 0.42 [0.62]) and of the posterior segment (2.38 [2.97] versus 0.35 [0.71] decreased significantly between baseline and the final visit (P < 0.001). The mean (SD) macular thickness at baseline was 304.54 (125.03) μ and at the end of follow-up was 230.87 (31.12) μ (P < 0.014). Baseline immunosuppression load was 8.10 (3.99) as compared with 5.08 (3.76) at the final visit (P < 0.001). The mean dose of corticosteroids also decreased from 0.25 (0.43) to 0 (0.02) mg (P < 0.001). No significant side effects requiring discontinuation of therapy were observed. Conclusion. Adalimumab seems to be an effective and safe treatment for JIA-associated refractory uveitis and may reduce steroid requirement.

Intravitreal plasmin without vitrectomy for macular edema secondary to branch retinal vein occlusion.

OBJECTIVES To evaluate the effects and safety of intravitreal injections of autologous plasmin enzyme (APE), without vitrectomy, as a treatment for macular edema secondary to branch retinal vein occlusion. DESIGN Prospective, comparative, interventional case series. METHODS Patients were recruited and enrolled consecutively from February 1 through October 31, 2008, at the Retina Unit of the Hospital General Universitario, Valencia, Spain. An eye from 8 patients diagnosed as having macular edema due to branch retinal vein occlusion received an injection, after having received topical anesthesia, of 0.2 mL of APE, which had been obtained using a simplified method. Best-corrected visual acuity and central macular thickness measured by optical coherence tomography constitute the main outcome measures of the study. RESULTS The mean (SD) central macular thickness decreased from 494.875 (68.82) to 226.375 (28.67) μm 1 month after APE injection and to 228.570 (21.53) μm after 6 months (P < .001). The best-corrected visual acuity (logarithm of the minimal angle of resolution) improved from a preoperative value of 0.552 (0.17) to 0.217 (0.087) (mean, 20/80-20/32, Snellen equivalent) at the end of follow-up (P < .01). No secondary effects were observed during 6 months of follow-up. CONCLUSION This pilot study suggests that intravitreal injection of APE as a treatment for macular edema secondary to branch retinal vein occlusion improves central macular thickness and best-corrected visual acuity and may be a safe and effective alternative therapy for this condition if confirmed in controlled trials compared with standard care with longer follow-up.