Taygan Yilmaz

Biological response modifier therapy for refractory childhood uveitis

Purpose: To evaluate the use of biological response modifiers (BRM) in the treatment of refractory childhood uveitis. Design: Retrospective non-comparative case series of pediatric patients with uveitis treated with BRM. Participants: 23 pediatric patients. Methods: All children (18 years or younger) who received a BRM were assessed for visual changes, time to control inflammation, and any associated adverse side effects. Thirteen patients were treated with infliximab, five with adalimumab, and five with daclizumab. All patients had bilateral eye involvement. Diagnoses of the participants included juvenile idiopathic arthritis, keratouveitis, sarcoid panuveitis, Adamantiades–Behcets disease, and idiopathic panuveitis. Main outcome measures: Inflammation and visual acuity. Results: In the infliximab group 16 of 26 eyes (62%), and 10 of 13 patients (77%) demonstrated an improvement in visual acuity. Twenty of 26 eyes (77%) demonstrated an improvement in the degree of inflammation. In the adalimumab group, four of 10 eyes (40%) demonstrated an improvement in visual acuity, with five of 10 eyes (50%) demonstrating an improvement in inflammation. Four of 10 eyes (40%) in the daclizumab group demonstrated an improvement in vision with eight of 10 eyes (80%) demonstrating an improvement in inflammation. Conclusion: BRM appear to be safe to use in children, and represent a useful therapeutic adjunctive drug group for treating recalcitrant childhood uveitides.

The characteristic features of optical coherence tomography in posterior uveitis

Aim: To describe the different retinal morphological characteristics that can present on optical coherence topography (OCT) in a spectrum of uveitic diseases. Methods: We reviewed the literature and our own OCT image archive for characteristic features that may be suggestive of a particular disease process. Results: OCT demonstrates a variety of characteristic morphological changes, some that may point towards a specific disease process. We describe the various forms of macular oedema found in uveitis as well as OCT features typically found in multifocal choroiditis, serpiginous chorioretinitis, toxoplasma chorioretinitis, Vogt–Koyanagi–Harada, sympathetic ophthalmia and the vitreomacular traction syndrome. Conclusion: Ophthalmologists should be aware of the variety of retinal morphological characteristics that can present on OCT in uveitic disease. Recognition may aid in the diagnostic process, which is complementary to conventional fundal photography and fluorescein angiography. This can facilitate earlier diagnosis and, more importantly, the initiation of specific treatment.

Intravitreal bevacizumab in refractory uveitic macular edema: one-year follow-up.

Purpose Uveitis is a major cause of ocular morbidity in developed countries. It has been demonstrated that macular edema is a significant cause of decreased visual acuity and macular edema in these patients. In this article, we evaluate the long-term outcome of intravitreal bevacizumab in the treatment of refractory uveitic macular edema. Methods In this retrospective, noncomparative, interventional case series, uveitic patients with macular edema who were refractory to conventional therapy and who were treated with intravitreal bevacizumab were identified and assessed. Best-corrected visual acuity and optical coherence tomography central macular thickness measurements were collected and analyzed with correlative statistical analysis, including the use of Student paired t-test, Kaplan-Meier, and linear regression analysis. Results Twenty-nine eyes of 27 patients with diverse uveitic etiologies were analyzed and followed up at 1 year. Thirteen patients received a single intravitreal bevacizumab injection. Six patients required a second intravitreal bevacizumab injection, while 10 patients received combination therapy of intravitreal bevacizumab and triamcinolone acetonide. Baseline mean logMAR visual acuity was −0.59. At 1 year, the mean logMAR visual acuity was −0.42± 0.36 (p=0.0045). Baseline mean central macular thickness was 383.66 μm. At 1 year, the mean thickness was 294.32±110.87 (p=0.0007). Conclusions Intravitreal bevacizumab is a useful and therapeutically beneficial agent in the treatment of refractory uveitic macular edema. Some patients will require adjunctive intravitreal bevacizumab injections or the use of combination therapy with intravitreal triamcinolone acetonide.

Combined therapy of cyclosporine A and mycophenolate mofetil for the treatment of birdshot retinochoroidopathy: a 12-month follow-up

Purpose To retrospectively report a 12-month follow up for combined therapy with systemic cyclosporine A (CSA) and mycophenolate mofetil (MM) in treatment of patients with birdshot retinochoroidopathy (BSRC). Participants Ninety-eight eyes of patients who received CSA and MM for the treatment of BSRC were included in the study. Methods All patients were followed for at least five visits during the study, or until treatment failure, or loss of follow-up. Clinical data were analysed using a Student paired t-test, Wilcoxon signed-rank test, McNemars test, and Kaplan -Meier survival curve. Side effects related to therapy were also recorded. Main outcome measures included best-corrected logarithm of the minimum angle of resolution visual acuity, vitreous inflammation, fluorescein angiography pathologic features, and electroretinogram recordings. Results Vitreous inflammation scores at baseline and at 1 year were statistically significantly reduced in both eyes (p<0.001; p=0.001). The presence of angiographic leakage at the 1-year follow-up was significantly reduced (p=0.004). However, the presence of cystoid macular oedema (p=0.32) and comparison of electroretinogram 30-Hz amplitude revealed no significant reduction between baseline and 1-year values for either eye (p=0.61, p=0.87); nonetheless, 30-Hz implicit times were statistically significantly shorter at the end of follow-up for both eyes (p<0.001, p=0.035). Thirty-one patients (67.4%) achieved inflammation control at the 1-year endpoint. Side effects were transient, and resolved after lowering or withholding IMT for a few weeks in the majority of patients. Conclusions These results suggest that combined IMT with CSA and MM for BSRC is well tolerated and associated with long-term control of inflammation.

The value of an immune response to Mycobacterium tuberculosis in patients with chronic posterior uveitides revisited: utility of the new IGRAs

PurposeTo explore the utility of a specific immune response to Mycobacterium tuberculosisin a population of immunosuppressed idiopathic chronic posterior uveitis patients, by means of a tuberculosis-specific interferon-γrelease assay.DesignProspective, interventional case series.MethodsA total of 31 referred patients with severe idiopathic chronic uveitis or panuveitis and 52 controls were screened for a specific immune response to tuberculosis. After ruling-out specific uveitis entities, presumed tuberculosis-related uveitis was initially considered when ophthalmologic findings were consistent with tubercular uveitis, and a specific immune response to M. tuberculosisconfirmed by QuantiFERON, despite inability to detect M. tuberculosis. Clinical responses to antitubercular treatment were recorded.Results:The prevalence of an immune response to M. tuberculosiswas 15.38% in controls and 32.25% in uveitis patients (OR=2.619, P=0.07). Two patients were QuantiFERON indeterminate (6.4%). After excluding seven specific uveitis entities (OR=3.66, P=0.03), eight QuantiFERON-positive and one QuanTIFERON-negative uveitis patients were initially treated for presumed tuberculosis-related uveitis. All but one had no evidence of active systemic involvement. None had been previously diagnosed with tuberculosis, but unsuccessfully treated with immunosuppressors. After a 9-month tuberculostatic treatment, seven QuantiFERON -positive and one QuantiFERON-negative patients exhibited decreased intraocular inflammation, visual acuity improvement, and no relapses. Estimated QuantiFERON sensitivity and specificity were 82 and 100%, respectively, with a PPV=100% and an NPV=86%.Conclusions:QuantiFERON was useful for antituberculous treatment decision-making in chronic posterior uveitis immunosuppressed patients from areas with an intermediate-high prevalence of tuberculosis.

Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review

To assess the effectiveness of ketorolac vs control for prevention of acute pseudophakic cystoid macular edema (CME). The following databases were searched: Medline (1950–June 11, 2011), The Cochrane Library (Issue 2, 2011), and the TRIP Database (up to 11 June 2011), using no language or other limits. Randomized controlled clinical trials (RCTs) were included that consisted of patients with acute pseudophakic cystoid macular edema, those comparing ketorolac with control, and those having at least a minimum follow-up of 28 days. In the four RCTs evaluating ketorolac vs control, treatment with ketorolac significantly reduced the risk of CME development at the end of treatment (∼4 weeks) compared to control (P=0.008; 95% confidence interval (0.03–0.58)). When analyzed individually, each individual study was statistically nonsignificant in its findings with the exception of one study. When the pooled relative risk was calculated, the large sample size of this systematic review led to overall statistical significance, which is attributable to the reviews large sample size and not to the individual studies themselves. In this systematic review of four RCTs, two of which compared ketorolac with no treatment and two of which evaluated ketorolac vs placebo drops, treatment with ketorolac significantly reduced the risk of developing CME at the end of ∼4 weeks of treatment compared with controls. These results, however, should be interpreted with caution considering the paucity of large randomized clinical trials in the literature.

Pars Plana Vitrectomy versus Immunomodulatory Therapy for Intermediate Uveitis: A Prospective, Randomized Pilot Study

Purpose: Comparison of pars plana vitrectomy (PPV) with immunomodulatory therapy (IMT) for patients with intermediate uveitis (IU). Methods: A prospective, randomized pilot study was performed on patients with recalcitrant IU associated with degradation of visual acuity (VA) despite standard treatment. Outcome measures (VA, intraocular pressure, anterior chamber and vitreous cellular infiltrate) were collected. Results: Sixteen patients (18 eyes) were randomized to the PPV IMT group. Nine of 11 eyes (82%) treated with PPV showed resolution of inflammation at follow-up, at 5.93 years. Four of 7 eyes (57%) given IMT had persistent inflammation requiring subsequent PPV. PPV patients showed greater improvement in Snellen line, IOP, and vitreous cell reduction. Three PPV patients had cystoid macular edema (CME) initially; all resolved postoperatively. CME improved in 2 of 3 eyes using IMT. Conclusions: A higher percentage of patients treated with PPV had improvement of uveitis compared to those given IMT. A multicentered clinical trial is needed to confirm and statistically validate these conclusions.

Systematic review of intravitreal bevacizumab injection for treatment of primary diabetic macular oedema.

Purpose:u2002 To compare intravitreal bevacizumab (IVB) injection versus macular photocoagulation (MPC) or a combination of intravitreal bevacizumab and intravitreal triamcinolone acetonide (IVB/IVTA) injection in improving visual acuity (VA) of patients with primary diabetic macular oedema (DMO).

Pharmacokinetics of triamcinolone acetonide for the treatment of macular edema

Introduction: The use of intravitreal triamcinolone acetonide (TA) for the treatment of various types of macular edema has been widespread, particularly for the last decade. Currently, there is a scant amount of evidence-based literature evaluating the pharmacokinetic profile of TA despite clinical data showing the efficacy of intravitreal TA for multiple forms of macular edema. Areas covered: This paper is an extensive review of human and experimental studies published on the pharmacokinetics of TA for the treatment of macular edema. The literature search was conducted via OVID, TRIP Database and EMBASE, up to April 2011. Expert opinion: The pharmacokinetic profile of TA is unpredictable and the agent has a time-limited therapeutic action due to its relatively short half-life. This has led to the need for repeated injections. Future research should investigate the pharmacokinetic profiles of TA when administered intravitreally, as well as through alternate routes in more robust studies.

Triamcinolone and intraocular sustained-release delivery systems in diabetic retinopathy.

Diabetic retinopathy (DR) still represents one of the leading causes of vision loss worldwide. Since this condition affects the posterior segment of the eye, topical application of ophthalmic medicines is of limited benefit, considering that they seldom reach therapeutic levels in the affected tissues. Systemic medications can be insufficient due to the eyes immunoprivileged condition and existence of both inner and outer blood-retinal barriers, which place limitations on the potential role of this route of administration for retinal diseases. In this setting, intraocular therapies have emerged as novel and vital tools in the ophthalmologists armamentarium against DR, allowing for maximization of drug efficacy and limited risk of systemic side effects. Intravitreal injections of triamcinolone acetonide have been widely used for treating DR particularly in the 21(st) century. Other agents targeting molecules, such as anti-vascular endothelial growth factor, have also demonstrated a potential therapeutic role for treatment. Recent advances in ocular drug delivery methods have led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drugs half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections.