Sumru Onal

Long-term Efficacy and Safety of Low-Dose and Dose-Escalating Interferon Alfa-2a Therapy in Refractory Behcet Uveitis

OBJECTIVE To investigate the long-term efficacy and safety of low-dose and dose-escalating therapy of interferon alfa-2a in the treatment of Behçet uveitis. METHODS This study included 37 patients with refractory Behçet panuveitis unresponsive to conventional immunosuppressive therapy. Induction interferon alfa-2a therapy was given as a daily dose of 3.0 million IU (MIU) subcutaneously for 14 days. Maintenance dose was achieved with 3.0 MIU 3 times per week given subcutaneously. The dosage was increased sequentially to 4.5, 6.0, and 9.0 MIU 3 times per week if uveitis relapses occurred. Total therapy duration was 24 months. Primary outcome measure was control of uveitis with quiescence during maintenance therapy. Ocular relapses per patient-year before and after initiation of interferon alfa-2a therapy and a corticosteroid-sparing effect were secondary outcomes. We also estimated the rate of remission after discontinuing interferon alfa-2a therapy. RESULTS During maintenance therapy, interferon alfa-2a controlled uveitis in 35 patients (95%). In 15 patients (41%), a maintenance dosage of 3.0 MIU 3 times per week controlled uveitis without any relapse. The rate of uveitis relapses decreased from 3.52 per patient-year before to 0.75 per patient-year after initiating interferon alfa-2a therapy. Seventeen patients were receiving systemic corticosteroids at the time of initiation of interferon therapy. During the maintenance stage, 9 patients were able to discontinue and 8 to taper systemic corticosteroid therapy. Survival analysis estimated that the rate of remission after discontinuation of interferon alfa-2a therapy was 76% by 3 months. The rate of remission remained stable thereafter. CONCLUSION A treatment protocol using a low-dose and dose-escalating therapy with interferon alfa-2a was able to control and achieve remission of uveitis in most patients with refractory ocular Behçet disease.

Systematic Review of Anti-Tumor Necrosis Factor-alpha Therapy for Treatment of Immune-mediated Uveitis

Purpose: To establish evidence-based recommendations regarding the use of anti-Tumor Necrosis Factor alpha (TNF-α) agents for managing uveitis patients. Methods: Medline was searched via OVID (1950 – October Week 3, 2011) using a Cochrane highly sensitive search (phases 1 and 2). Additional literature searches were also conducted incuding the following databases: the Cochrane, LILACS and the TRIP Database. Results: A total of 54 studies met all of the inclusion criteria and were included in this review. A different level of recommendation and evidence is assigned to each anti-TNF-α agent. The overall rate of reported side effects with anti-TNF-α agents for the treatment of uvetis which required discontinuation of therapy was 2.2% (26/1147 patients). Conclusion: Based on the evidence gathered, infliximab and adalimumab seem to be effective in the management of immune-mediated uveitis. Further randomized studies evaluating the efficacy of these agents are warranted.

Optical coherence tomography imaging in uveitis

Optical coherence tomography (OCT) is a non-contact noninvasive technique that allows in vivo imaging of the retina, choroid, optic nerve head, retinal nerve fiber layer, and the anterior structures of the eye. It was introduced into clinical practice two decades ago. Advances in OCT technology have been achieved by searching ultra-high-resolution OCT, adaptive optics OCT, eye-tracking OCT, and changes in signal detection technique from time-domain (TD) to spectral-domain (SD) detection. Today, SD OCT has become a part of routine uveitis practice. Apart from its diagnostic value in uveitis, OCT has enabled objective assessment of treatment response and provided predictive value for visual recovery and prognosis of uveitic entities. It is the standard diagnostic technique in the detection, monitoring of treatment, and determination of prognosis in uveitic macular edema as well as other inflammatory macular pathologies, including epiretinal membrane formation, vitreomacular traction, foveal atrophy, and lamellar/full-thickness macular holes. OCT has also shed light on the pathophysiology of several posterior uveitic entities. SD OCT has enabled visualization of four lines in the sensory retina which represent the external limiting membrane, the photoreceptor inner and outer segment junction, the photoreceptor outer segment and the retina pigment epithelium junction, and the retina pigment epithelium−choriocapillaris complex. Thus, we have gained substantial information about the pathologic and structural changes in uveitic conditions with primary or secondary outer retinal involvement. SD OCT has also provided invaluable information on the inner retinal and the vitreoretinal interface changes in uveitic conditions. With the introduction of enhanced depth imaging, visualization of the choroid and choriocapillaries has become possible. Therefore, OCT has become an indispensible ancillary test in the diagnosis and management of inflammatory diseases involving the retina and/or the choroid. As OCT technology continues to develop further it will provide new insights into the retinal and choroidal structure and the pathogenesis of posterior uveitic entities.

Bilateral acute iris transillumination

OBJECTIVE To describe a series of patients with bilateral acute iris transillumination, pigment dispersion, and sphincter paralysis. METHODS We reviewed the medical records and clinical photographs of 26 patients seen at 5 centers in Turkey and Belgium between March 16, 2006, and July 6, 2010. Observation procedures included clinical examination, anterior segment color photography, gonioscopy, laser flare photometry, and pupillometry. RESULTS All 26 patients (20 women and 6 men; mean [SD] age, 43.2 [10.5] years) had bilateral involvement. Twenty-three patients (88%) had acute-onset disease with severe photophobia and red eyes. Nineteen patients (73%) had a preceding flulike illness and used systemic antibiotics, including moxifloxacin. Diagnostic laboratory workup was unremarkable. There was pigment discharge into the anterior chamber, and flare was elevated in the absence of inflammatory cells. Most patients had severe diffuse transillumination of the iris and mydriatic distorted pupils. Pupillometry revealed a compromised reaction to light. The most serious complication was an intractable early rise in intraocular pressure. Gonioscopy revealed heavy pigment deposition in the trabecular meshwork. Although symptoms were relieved promptly by application of topical corticosteroid, the median duration of pigment dispersion was 5.25 months. CONCLUSIONS Bilateral acute iris transillumination with pigment dispersion and persistent mydriasis is a new clinical entity that is not an ocular adverse effect of oral moxifloxacin treatment, as previously suggested. The etiopathogenesis of this entity remains to be elucidated.

Vision- and health-related quality of life in patients with Behçet uveitis.

OBJECTIVE To investigate vision- and health-related quality of life in patients with Behçet disease. METHODS Fifty-one consecutive patients with Behçet uveitis were enrolled in the study from January 1 through June 30, 2008. The National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and the 36-Item Short Form Health Survey (SF-36) were administered. Sociodemographic and clinical data were also collected. Main outcome measures were comparison of the NEI-VFQ-25 and SF-36 subscale item scores among subgroups and multivariate analysis of the NEI-VFQ-25 and SF-36 subscale item scores. RESULTS Patients rated the general health subscale score of the NEI-VFQ-25 and all subscale item scores of the SF-36 lower than the NEI-VFQ-25 subscales related to vision. The NEI-VFQ-25 subscale item scores showed significant differences with respect to age, educational level, Behçet uveitis activity and severity, and visual acuity in the better and worse eyes. The SF-36 subscale item scores revealed significant differences according to sex, educational level, and the systemic treatment used. In the best model of linear regression, independent variables accounted for 57.0% of the variance in the NEI-VFQ-25 subscale item (color vision subscale; adjusted R² = 0.57, P < .001) and for only 23.0% of the variance in the SF-36 subscale item score (role limitation owing to emotional problems subscale; adjusted R² = 0.23, P = .004). CONCLUSIONS General health is more affected than visual functioning in patients with Behçet uveitis. Sociodemographic and clinical variables had a significant effect on vision- and health-related quality of life. Multivariate analysis of the NEI-VFQ-25 and SF-36 subscales revealed that each subscale item score is affected by additional factor(s) other than those analyzed here.

Comparison of Presenting Features and Three-year Disease Course in Turkish Patients with Behçet Uveitis Who Presented in the Early 1990s and the Early 2000s

Purpose: To compare Behçet uveitis patients who presented in the 1990s and 2000s. Methods: Records of 170 patients seen in 1990–1994 and 258 patients seen in 2000–2004 were reviewed. Presenting features were analyzed in the whole cohort. Uveitis attacks, vision, complications, and immunomodulatory treatment (IMT) were compared in patients with 3-year follow-up. Results: Posterior segment involvement was less common, visual acuity was better, and more patients received IMT before referral in the 2000s. Follow-up revealed no significant difference in number of uveitis attacks in the first 3 years. Less eyes lost useful vision, no patient became legally blind, and fewer severe ocular complications occurred in the 2000s. IMT was started within 3 months in more patients and interferon alfa-2a was used only in the latter study period. Conclusions: The findings suggest a milder disease at referral, lower rate of severe complications, and a better 3-year visual outcome in patients who presented in the early 2000s.

Pars Plana Vitrectomy and Intravitreal Liposomal Amphotericin B in the Treatment of Candida Endophthalmitis.

Candida endophthalmitis is a common cause of fungal endophthalmitis. A case of bilateral endogenous endophthalmitis caused by Candida albicans without candidemia in an otherwise healthy 77-year-old man was reported. The patient underwent bilateral pars plana vitrectomy and intravitreal liposomal amphotericin B injections in addition to systemic fluconazole therapy. Postoperatively, a significant decrease of inflammation and resolution of abscesses were observed in both eyes. Vision improved in the left eye but remained constant in the right eye because of secondary cataract formation. To the best of our knowledge, this is the first report on the use of liposomal amphotericin B intravitreally in a patient with bilateral endogenous candida endophthalmitis. No evidence of clinical ocular toxicity was observed with the liposomal form of amphotericin B injection.

Analysis of age, refractive error and gender related changes of the cornea and the anterior segment of the eye with Scheimpflug imaging

PURPOSE To assess age, refractive error and gender related changes occurring in the cornea and the anterior segment of the eye using a Scheimpflug system. METHODS The study included 666 healthy eyed subjects with a mean age of 39.3±19.7 years (range: 3-85 years). All analyses were based on the right eyes of the patients as all measured parameters correlated well between the right and left eyes. Each parameter was correlated with age and the right eyes spherical equivalent (SE) using Pearson correlations. Univariate linear regression models were constructed for analyses of parameters. RESULTS The anterior corneal surface asphericity showed significant positive correlations whereas posterior corneal surface asphericity showed significant negative correlations with age. Anterior chamber depth (ACD), volume (ACV) and angle (ACA) showed significant negative correlations with age and SE. Age explained 25% of the variance in anterior corneal surface asphericity, 22% of variance in posterior corneal surface asphericity, 26% of variance in ACV, 27% of variance in ACD, and 19% of variance in ACA. In the SE model SE was identified to account for 25% of variance in ACV, 22% of variance in ACD, each, and 17% of variance in ACA. Significant differences were detected in anterior and posterior keratometry values, ACV, ACD and ACA among gender groups (p<0.01). CONCLUSIONS The cornea shows a tendency for a decrease in anterior corneal surface asphericity and an increase in posterior corneal surface asphericity with advancing age. Men have flatter corneas and women have shallower anterior chambers and narrower anterior chamber angles.

Review for Diagnostics of the Year: Multimodal Imaging in Behçet Uveitis.

ABSTRACT Behçet disease is a chronic relapsing multisystem inflammatory disorder. Ocular involvement is characterized by a bilateral recurrent non-granulomatous panuveitis and retinal vasculitis. Posterior segment findings vary during the course of the disease, in parallel with the relapsing and remitting intraocular inflammation. Structural alterations occur with increased disease duration. Fluorescein angiography is the gold standard in revealing the extent and severity as well as the leaky and/or occlusive nature of retinal vasculitis. Multimodal imaging using color fundus photography, fluorescein angiography, and optical coherence tomography is essential in visualizing diagnostic features, detecting structural changes, and monitoring disease activity and response to treatment in patients with Behçet uveitis.

Electroretinographic improvement after rituximab therapy in a patient with autoimmune retinopathy

Purpose To describe the effect of rituximab on full-field electroretinography (ERG) in a patient with nonparaneoplastic autoimmune retinopathy (npAIR). Observations A 58-year-old male patient with visual complaints, positive anti-retinal antibodies and negative work-up for cancer was diagnosed with npAIR. Visual acuity and ancillary tests were normal except abnormal ERG in both eyes. The patient was given one course of rituximab 375 mg/m2/week for 4 weeks and cyclophosphamide 1 gr/m2/month for 6 months. A second course of rituximab was necessary as autoantibody titers showed no change and as new antibodies were noted after treatment with rituximab and cyclophosphamide. Electroretinography was repeated after the first course of rituximab, after cyclophosphamide, and the second course of rituximab therapy. Conclusions and importance Rituximab therapy led to marked improvement in full-field ERG readings and regression of symptoms was reported by the patient after rituximab infusions. The effect of rituximab in npAIR was objectively demonstrated with ERG.