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Purpose: To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis. Design: Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE. Participants: A total of 118 patients with Behçet''s uveitis (SHIELD study); 31 patients with active, noninfectious, non–Behçet''s uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non–Behçet''s uveitis (ENDURE study) were enrolled. Methods: After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study. Main Outcome Measures: Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes. Results: After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies. Conclusions: The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: We aimed to describe the demographic and clinical features, ocular manifestations, complications, visual prognosis, and treatment in a large population of Turkish patients with Behçet uveitis. We also aimed to compare visual prognosis between male and female sex and between patients who presented before and after 1990.Design: Observational case series.Methods: A retrospective study of 880 consecutive patients (1,567 eyes) with Behçet uveitis seen at the Uveitis Service, Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, from 1980 to 1998. All patients met the classification criteria of the International Study Group for Behçet''s Disease. Information on the patient''s sex, age at onset of uveitis, ocular features, ocular complications, visual acuity, and systemic treatment was collected.Results: Five hundred ninety-nine patients (68%) were male and 281 (32%) were female. The mean age at onset of uveitis was 28.5 years in male and 30 years in female patients. Ocular involvement was bilateral in 78.1% and unilateral in 21.9% of the patients. Panuveitis was the most common form in both sexes. Fundus lesions as well as sight-threatening complications were more common in males. At the beginning of the follow-up, potential visual acuity was 0.1 or less in 30.9% of eyes in males and 24.2% of eyes in females. Kaplan-Meier survival analysis estimated the risks of losing useful vision (>0.1) at 5 and 10 years for males and females as 21% vs 10% and 30% vs 17%, respectively. Male patients who presented in the 1990s had a significantly lower risk of losing vision compared with male patients who presented in the 1980s.Conclusion: Behçet uveitis starts frequently around the end of the third decade and has a male predominance. The disease is more severe and the risk of losing useful vision is higher in males than in females. However, this risk has been significantly reduced in the 1990s. [Copyright &y& Elsevier]

: PurposeTo describe the demographic and clinical features, complications, treatment, and visual results in patients with childhood-onset Behc¸et uveitis.: DesignObservational case series.: MethodsA retrospective study was made of 36 consecutive patients with Behc¸et disease seen at the Uveitis Service, Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, between January 1975 and January 2002. Inclusion criteria were fulfillment of the classification criteria of the International Study Group for Behc¸et Disease and onset of uveitis at 16 years of age or younger. The medical records of 36 patients with childhood-onset Behc¸et uveitis were reviewed. The main outcome measures were sex, age at onset of uveitis, the initial symptom of Behc¸et disease, clinical ocular features, ocular complications, systemic treatment, complications of treatment, and final visual acuity.: ResultsTwenty-five patients were male, 11 were female. Mean age at onset of uveitis was 13.6 years. The initial symptom was oral ulcer in 63.8% of the patients. The majority of patients (83.3%) had bilateral involvement. Panuveitis was the most common form (86.2%). Retinal vasculitis and retinitis were the most common ocular findings seen in 83.3% and 68.2% of the involved eyes, respectively. Cataract, maculopathy, and optic atrophy were the most common complications seen in 46.9%, 45.4%, and 39.4% of the involved eyes, respectively. Immunosuppressive therapy was administered to 75% of the patients. Response to treatment was variable. The most common complications of systemic treatment were associated with corticosteroid therapy. Final visual acuity was worse than 0.1 in 22.7% of the involved eyes.: ConclusionsChildhood-onset Behc¸et uveitis was more common among males. Bilateral panuveitis with retinal vasculitis and retinitis was the most common form of ocular involvement, similar to the adult patient. The treatment is challenging, as the use oral corticosteroids is associated with significant complications and the response to conventional immunosuppressive therapy is variable. [Copyright &y& Elsevier]

Tumor necrosis factor-alpha (TNF-α) antagonists have been successfully used in refractory cases of pediatric uveitis. We report our experience with the monoclonal anti-TNF-α antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.▪ [Copyright &y& Elsevier]

Purpose: To describe Turkish patients with Fuchs uveitis syndrome (FUS). Design: Retrospective observational case series. Methods: We reviewed the records of 172 patients with FUS seen at Istanbul University, Istanbul Faculty of Medicine, Department of Ophthalmology, between January 1995 and July 2007. The main outcome measures were demographic features, clinical findings at presentation, laser flare photometry values, risk of new complications, and rate of decreased vision. Results: The mean age was 29.5 + 8.4 years. Male-to-female ratio was 1:1.3. Nine patients (5.2%) had bilateral involvement. The diagnosis of FUS had been made in only 10 of 115 (8.7%) referrals. Clinical findings at presentation included diffuse keratic precipitates (medium-sized round in 74.6%, fine-stellate in 22.1%), anterior chamber cells (74%), diffuse iris atrophy without hypochromia (48.6%), heterochromia (39.8%), iris nodules (32%), cataract/pseudophakia (69.1%), vitreous cells (71.8%), elevated intraocular pressure (12.7%), and chorioretinal scars (7.7%). The mean flare was 8.4 + 3.1 photons/ms in eyes with FUS and 3.7 + 0.8 photons/ms in the fellow eyes (P < .001). Hyperfluorescence of the optic disc was the only fluorescein angiographic finding, detected in 7 of 32 eyes (22%). Kaplan-Meier analysis estimated risks of cataract formation and intraocular pressure elevation as 42% and 17%, respectively, at 4 years. The rate of decreased visual acuity by 2 lines or more was 0.06/eye-year. Conclusions: The referral patterns suggest that FUS is frequently misdiagnosed in Turkish patients. Diffuse medium-sized round keratic precipitates, low flare readings, iris stromal atrophy without hypochromia, and vitreous opacities in the absence of macular edema are more often helpful clues to the diagnosis than heterochromia. [Copyright &y& Elsevier]

Purpose: To report new cases of bilateral acute depigmentation of the iris (BADI), a recently described clinical entity, and to report the 4-year follow-up of 2 patients that was published previously. Design: A retrospective case series. Participants: Twenty-six Turkish patients who were diagnosed with BADI between 2006 and 2008 and 2 patients who were reported previously. Methods: We reviewed the patients'' charts and clinical photographs. Observation procedures included clinical examination, anterior segment color photography, laser flare photometry, and pupillometry. We performed an anterior chamber tap in 2 patients for polymerase chain reaction (PCR) to demonstrate the DNA of herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) in the aqueous samples. Main Outcome Measures: Demographic features, presenting symptoms, laboratory findings, changes in iris stromal pigment and architecture, and time to resolution of pigment dispersion in the anterior chamber. Results: Nineteen patients were female, and 7 patients were male. Mean age was 32.3±8.6 years. All had bilateral involvement. Twenty patients (76.9%) presented with photophobia and red eyes, and 4 patients (15.4%) presented with a recent change in eye color. Ten patients (38.5%) had flu-like symptoms preceding the onset of ocular symptoms. Diagnostic laboratory workup, viral serology, and PCR analysis of the aqueous humor were unrewarding. Diffuse depigmentation of the iris stroma from the collarette to the iris root was seen in 16 patients, and geographic areas of depigmentation were seen in 10 patients. There was heavy pigment deposition in the trabecular meshwork in all patients. Anterior chamber flare was elevated in eyes with circulating pigment. The pupil was not affected. Twenty patients received topical corticosteroids. Pigment dispersion resolved in 1 to 16 weeks (median, 9 weeks). The intraocular pressure was elevated in 8 steroid-treated eyes but was controlled with antiglaucomatous medications. In 2 patients reported previously, the depigmented iris stroma became repigmented after 4 years. Conclusions: Patients with BADI present with bilateral, symmetrical, nontransilluminating depigmentation of the iris stroma and pigment discharge into the anterior chamber. Young female persons are more commonly affected. The cause remains unknown. After 4 years, the ocular findings in 2 patients normalized. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

: PurposeTo describe the occurrence of conjunctival ulcers as a manifestation of Behc¸et’s disease.: DesignRetrospective, noncomparative, interventional case series with histopathologic correlation.: MethodsSix patients who fulfilled the diagnostic criteria for Behc¸et’s disease and presented with painful conjunctival ulcers were included in the study. Three of these ulcers were biopsied and studied histologically and immunohistochemically. The lesions were treated with topical or subconjunctival injection of corticosteroids and, in one case, with oral indomethacin.: ResultsAlthough all six patients fulfilled the diagnostic criteria for Behc¸et’s disease, two developed uveitis and other signs of Behc¸et’s disease only months to years after the appearance of the conjunctival ulcers. The 3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both acute and chronic inflammatory cells, and high endothelial venules. Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T-cell populations admixed with several B cells and CD68-positive histiocytes. After treatment, the conjunctival lesions invariably healed without scarring.: ConclusionsIn addition to the oral and genital ulceration, ulcers can also be found in the conjunctiva of patients with Behc¸et’s disease. Although this is a rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may suggest a diagnosis of Behc¸et’s disease. [Copyright &y& Elsevier]

Aim To outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy. Method The approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease. Conclusion We recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects. [ABSTRACT FROM AUTHOR]

PURPOSE: To describe nonglaucomatous retinal nerve fiber layer (RNFL) defects in patients with Behcet uveitis. DESIGN: Cross-sectional study and observational case series. METHODS: We reviewed the clinical photographs of patients with Behcet uveitis (n = 259), ocular toxoplasmosis (n = 120), and multiple sclerosis (MS)-associated uveitis (n = 40) for the presence of localized RNFL defects. Behcet patients with localized RNFL defects were invited to participate in a prospective evaluation including standard automated perimetry, spectraldomain optical coherence tomography (SD OCT), and RNFL thickness analysis. Main outcome measures were the prevalence of localized RNFL defects, perimetric and SD OCT findings, and RNFL thickness analysis. RESULTS: Sixty-two patients with Behcet uveitis (24%) had localized RNFL defect(s) without any visible scar. Twenty patients (17%) with ocular toxoplasmosis had a localized RNFL defect associated with a retinochoroidal scar in all. None of the MS patients had a localized RNFL defect. Of the 19 patients (24 eyes) with RNFL defect associated with Behcet uveitis who returned for follow-up, there was a corollary thinning on SD OCT B-scan in all and a corresponding visual field defect in 83%. RNFL thickness analysis was within normal limits in 54%, but revealed thinning in the thickness profile scale in 46% and in the pie chart in 21%. CONCLUSION: In Behcet uveitis, localized RNFL defects may be caused by microvascular ischemia at the optic nerve head and/or at the posterior pole and may serve as a helpful ocular diagnostic clue and an indicator of posterior pole involvement, a risk factor for poor visual prognosis. [ABSTRACT FROM AUTHOR]