Health-care delivery is a complex and fragmented system with work-around culture. Improving health-care delivery requires innovating system interventions that redesign processes for consistent implementation of evidence-based practices (EBPs). Systems engineering is an approach that involves anticipating ineffective processes that jeopardize quality, and designing interventions to overcome such shortcomings. This approach is based on systems teaching about reflexivity, which when addressed can support consistent EBP and assesses how the newly designed system meets this consistency. Integrating a systems engineering approach to implementing EBP may effectively address complex issues such as hospital-acquired pressure ulcer prevention, which has an EBP protocol that is not consistently implemented without system redesign. Engineering approaches and methods including Plan-Do-Study-Act (PDSA), Situation-Background-Assessment-Recommendations (SBAR), stochastic modeling, House of Quality, and statistical process control charts with lean six sigma provide a structured approach to identifying points of successful implementation for EBPs that can subvert work-around culture. This perspective piece reviews successful approaches of systems engineering to solve the problem of clinical work-arounds and puts forward the case for its wider application to health-care delivery systems that could benefit from standardized EBPs.
Introduction: Drug-induced uveitis is a well described but often overlooked and/or misdiagnosed adverse reaction to medication. There are an increasing number of medications that have been related to the onset of intraocular inflammation. Identification of these inciting agents may decisively help the diagnostic algorithm involving new cases of uveitis.Areas covered: This review intends to be an updated comprehensive, practical guide for practitioners regarding the main drugs that have been associated with uveitis. A classification proposed by Naranjo et al. in 1981 for establishing potential causality is applied examining possible mechanisms of action. A guide for clinicians about the rationale of these observations when dealing with patients with uveitis is provided.Expert opinion: Several agents with different routes of administration (systemic, topical and/or intraocular) may cause intraocular inflammation. The mechanism behind ocular inflammation is frequently unknown. Clinicians should be aware of the potential drug effect to optimize diagnosis and management of such patients.
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.
Introduction: Management of patients with severe immune-mediated uveitis requires the use of immunosuppressive drugs in selected cases. This may be especially challenging in certain patients with concomitant conditions, which could increase the risk of side effects or modify guidelines for the use of such drugs. Therapeutic decision-making and management may be of particular difficulty in pregnancy as well as in patients with associated malignancies unrelated to a specific ophthalmic inflammatory condition.Areas covered: The main aim of this review is to provide an updated comprehensive practical guide for practitioners regarding the therapeutic decision-making and management of patients with severe immune-mediated uveitis in the context of pregnancy and malignancies.Expert opinion: Management of patients with immune-mediated uveitis requiring immunosuppressive/immunomodulatory drugs might be particularly complicated by other conditions affecting their health and immune status. Clinicians should take into account such conditions, which might influence treatment response and the clinical outcome of these patients.
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.
Introduction: Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches.Areas covered: Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research.Expert opinion: Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.
Background: Approximately 3.75% of cases of blindness in the United States are caused by uveitis. Incurred clinical costs and lost productivity related to vision loss in these cases totals $3.58 billion annually. Objective: To evaluate whether infliximab, a modern off-label biologic, is cost-effective for treating posterior uveitis and panuveitis compared to current standards of care, methotrexate and prednisone. Methods: A cost-effectiveness analysis using a Markov model to simulate a patient cohort with posterior uveitis or panuveitis. The model followed patients' therapy from the onset of posterior uveitis or panuveitis using the U.S. societal perspective. The lifetime model simulated health states that could lead to successful reversal of uveitis with standard or intensified treatment with prednisone, methotrexate, or infliximab. Probabilities, health utilities, and costs were included in the model based on findings from the literature. We conducted univariate sensitivity analyses and a Bayesian multivariate probablistic sensitivity analysis to estimate uncertainty in results. Outcomes were measured in terms of costs ($US, 2010) and effects (qualityadjusted life years; QALYs) discounted at 3% per year were estimated for each simulated treatment. An incremental cost-effectiveness ratio (ICER) for pairwise results was interpretted assuming a predetermined willingness-to-pay threshold of $100,000/QALY. Results: Average lifetime costs and QALYs for each drug were ($306.95; 15.80 QALYs) for prednisone, methotrexate ($36,232.24; 16.21 QALYs), and inflixmab ($74,762.63; 15.04 QALYs). Methotrexate was on average compared to prednisone, with an ICER of $86,901.16/QALY. Prednisone and methotrexate dominated infliximab. Sensitivity analyses suggested that the model was most sensitive to the utility for successful recovery from uveitis. The probabilistic sensitivity analysis returned results similar to the base case. Conclusion: This cost-effectiveness analysis suggests that despite advances in the use of biologics for treating sight-threatening posterior uveitis and panuveitis, infliximab had lower effectiveness and higher costs compared to both prednisone and methotrexate. As compared to prednisone, methotrexate was associated with increased costs and QALYs and was found to be a good value. Clinical trials of infliximab in the uveitis population are needed to reduce the uncertain estimates of inflixmab treatment success and the drug's cost-effectiveness.
