Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up

Curcumin has been successfully applied to treat inflammatory conditions in experimental research and in clinical trials. The purpose of our study is to evaluate the efficacy of an adjunctive-to-traditional treatment with Norflo tablets (curcumin-phosphatidylcholine complex; Meriva) administered twice a day in recurrent anterior uveitis of different etiologies. The study group consisted of 106 patients who completed a 12-month follow-up therapeutic period. We divided the patients into three main groups of different uveitis origin: group 1 (autoimmune uveitis), group 2 (herpetic uveitis), and group 3 (different etiologies of uveitis). The primary end point of our work was the evaluation of relapse frequency in all treated patients, before and after Norflo treatment, followed by the number of relapses in the three etiological groups. Wilcoxon signed-rank test showed a P < 0.001 in all groups. The secondary end points were the evaluation of relapse severity and of the overall quality of life. The results showed that Norflo was well tolerated and could reduce eye discomfort symptoms and signs after a few weeks of treatment in more than 80% of patients. In conclusion, our study is the first to report the potential therapeutic role of curcumin and its efficacy in eye relapsing diseases, such as anterior uveitis, and points out other promising curcumin-related benefits in eye inflammatory and degenerative conditions, such as dry eye, maculopathy, glaucoma, and diabetic retinopathy

New pharmacotherapy options for noninfectious posterior uveitis

Introduction: Noninfectious inflammation of the posterior eye segment represents an important cause of visual impairment. It often affects relatively young people and causes a significant personal and social impact. Although steroids and nonbiologic- Disease-Modifying Antirheumatic Drugs (nbDMARDs) are effective both in acute and long- lasting diseases, however they are increasingly being replaced by biologic (DMARDs). bDMARD. This article therefore aims to identify recent advances in the therapy of noninfectious posterior segment uveitis. Methods: A Medline-search was conducted using the terms: nbDMARD, bDMARD, posterior uveitis, intermediate uveitis, treatment, corticosteroid. In addition, clinical studies were included as registered at ClinicalTrials.gov. Results: Currently two major lines of treatments can be identified: (1) the intraocular application of anti-inflammatory agents and (2) the introduction of new agents, e.g., (bDMARDs) and small-molecule-inhibitors. Whereas intravitreal treatments have the advantage to avoid systemic side effects, new systemic agents are progressively earning credit on the basis of their therapeutic effects. Conclusion: Even when current treatment strategies are still hampered by the limited number of randomized controlled trials, promising progress and continuous efforts are seen

Myopia and Inflammation

The correlation between myopia and intraocular inflammation has rarely been explored. The aim of this article is to review myopic changes induced by inflammatory diseases and inflammatory diseases related to myopia, followed by a discussion on inflammatory choroidal neovascularization. Clinical cases are used to illustrate these conditions. The review does not include inflammatory conditions caused by surgical interventions employed for treatment of myopia. Uveitic conditions that can induce a myopic shift include sclero-choroidal inflammation, lens induced myopia due to steroid cataracts, juvenile idiopathic arthritis (JIA) induced myopia, and transient drug induced myopia due to sulfonamides and acetazolamide used for treatment of ocular toxoplasmosis and inflammatory cystoid macular edema, respectively. Most inflammatory conditions related to myopia are conditions involving the choriocapillaris. These include multifocal choroiditis and/or punctate inner choroiditis, multiple evanescent white dot syndrome and acute idiopathic blind spot enlargement. It can be hypothesized that fragility of the choriocapillaris due to particular anatomic changes due to myopia, together with unknown immunogenetic factors predispose myopic eyes to primary inflammatory choriocapillaropathies

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making

Biologic Agents in Inflammatory Eye Disease

Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, there is still lack of randomized controlled trials to validate most of their applications. Biologics are promising drugs for the treatment of uveitis, showing a favorable safety and efficacy profile. On the other hand, lack of evidence from randomized controlled studies limits our understanding as to when commence treatment, which agent to choose, and how long to continue therapy. In addition, high cost and the potential for serious and unpredictable complications have very often limited their use in uveitis refractory to traditional immunosuppressive therapy

Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography

Background: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. Methods: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. Results: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3, and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. Conclusions: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber

Cost-effectiveness of intravitreal therapy in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies. Anti-VEGFs currently used to treat AMD included a monoclonal antibody (bevacizumab), an antibody fragments (ranibizumab), a fusion protein (aflibercept), and an aptamer (pegaptanib). The wide introduction of anti-VEGF therapy has led to an improvement in the prognosis of patients affected by AMD, with a consequent effects on the burden of care due to highly priced drugs, increasing patient numbers, and long-term disease chronicity. Aim of this review is to present an overview of available therapeutic strategies in AMD in term of clinical efficacy and economic sustainability

Non-infectious uveitis burden on quality of life and work impairment assessed through different psychometric questionnaires

Background: The purpose of this study was to evaluate the association between a novel psychometric 12-item questionnaire (U-qest) and other validated questionnaires to assess quality of life and work impairment in patients with non-infectious uveitis. Methods: Data were collected at baseline and 3 months postbaseline using U-qest and two other validated questionnaires: The National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and the 12-Item Short-Form Health Survey (SF-12). Results: A total of 136 patients (52.2% female) aged 47.9 ± 14.8 years (mean ± SD) were enrolled in 14 uveitis referral centres. U-qest correlated moderately with VFQ-25 and SF-12 at baseline and at 3 months. Both U-qest and VFQ-25 scores improved as disease improved; however, U-qest also detected improvement in patients for whom VFQ-25 scores did not improve. Disease activity was shown to significantly affect activity impairment. Patients and physicians expressed positive perceptions regarding the use and benefit of this instrument. U-qest showed very good reliability in terms of internal consistency (Cronbach’s alpha = 0.91). Conclusions: U-qest can be considered a useful tool to assess the burden of uveitis on quality of life

Discordance between patient and physician global assessment of disease activity in Behçet's syndrome: a multicenter study cohort

Background: To compare the patients' and physician's global assessment of disease activity in Behçet's syndrome (BS) and investigate the frequency, magnitude, and determinants of potential discordance. Methods: A total of 226 adult BS patients with a median (IQR) age of 46.9 (35.6-55.2) years were enrolled across Italy, Greece, Portugal, and Spain. Demographic, clinical, and therapeutic variables, as well as the patient reported outcomes, were collected at the recruitment visit. The physical (PCS) and mental (MCS) component summary scores of the Short Form Questionnaire 36 (SF-36) and the Behçet's syndrome Overall Damage Index (BODI) were calculated. Disease activity was assessed by the patients' (PtGA) and physician's global assessment (PGA) in a 10-cm visual analog scale, as well as the Behçet Disease Current Activity Form (BDCAF). Discordance (∆) was calculated by subtracting the PGA from the PtGA and defined as positive (PtGA>PGA) and negative (PtGA 80%) of disagreements were due to patients rating higher their disease activity. Higher values of BDCAF were associated to increased rate of positive discordance. When BDCAF = 0, the median (IQR) values of PtGA and PGA were 0.2 (0-2) and 0 (0-1), respectively. PCS (adjusted odds ratio (adjOR) 0.96 per unit, 95% CI 0.93-0.98, p = 0.006) and MCS (adjOR 0.96 per unit, 95% CI 0.93-0.99, p = 0.003) were independently associated with positive discordance using both cutoffs. Active ocular involvement emerged as a potential determinant of negative discordance (adjOR 5.88, 95% CI 1.48-23.30, p = 0.012). Conclusions: PtGA and PGA should be considered as complementary measures in BS, as patients and physicians may be influenced by different factors when assessing active disease manifestations. Particularly, PtGA may be a useful tool in the assessment of BS disease activity, as it carries a low risk to misclassify an inactive disease, and may allow to capture aspects of the patient's health that negatively affect his well-being and the treatment

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents