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

Adalimumab therapy of noninfectious uveitis

Nieinfekcyjne zapalenia błony naczyniowej (NZBN) stanowią problem diagnostyczny i terapeutyczny, mają przewlekły i kumulacyjny charakter, a także są przyczyną znaczącej utraty funkcji wzroku u młodych osób, uniemożliwiającej aktywność zawodową. Diagnostyka i leczenie wymagają współpracy specjalistów z różnych dziedzin i opierają się na licznych badaniach laboratoryjnych i obrazowych. Praca przedstawia wskazania, efektywność i bezpieczeństwo terapii pierwszym lekiem biologicznym stosowanym w okulistyce, jakim jest inhibitor czynnika martwicy guza α, adalimumab. Może być on uznany za istotną opcję terapeutyczną w leczeniu zapalenia błony naczyniowej części pośredniej i tylnej, a także zapalenia wszystkich części błony naczyniowej, ponieważ pozwala pacjentom na osiągnięcie i utrzymanie długotrwałej kontroli nad chorobą przy jednoczesnej terapii glikokortykosteroidami czy lekami immunomodulującymi lub jej braku.Noninfectious uveitis is known for its chronic and cumulative nature. It is often associated with diagnostic and therapeutic difficulties. It causes significant vision loss in young patients, making them incapable of maintaining an active work life. Diagnosis and treatment require cooperation between different specialists and are based on multiple blood tests and other diagnostic tests. This article presents medical indications and the safety and efficacy of adalimumab, a tumor necrosis factor inhibitor and the first biological drug used in ophthalmology. Adalimumab is an important therapeutic option for the treatment of intermediate, posterior, and pan-uveitis, enabling patients to obtain and maintain long-term disease control during simultaneous corticosteroid/immunomodulatory therapy or without it

Ocular Manifestations of Behçet’s Disease: An Update on Diagnostic Challenges and Disease Management

Behçet’s disease is a systemic vasculitis that affects multiple organs. The most common manifestations are oral and genital ulcerations and recurrent uveitis. Uveitis can be an initial symptom in 10–20% of cases and leads to blindness in 16–25% of patients. The management of this disease is evolving due to the clinical phenotypes recently described in the literature and increasing focus on the detection of subclinical inflammation to enable correct therapeutic decisions. The first line treatment is azathioprine, followed by various immunosuppressive and biological agents as alternatives in severe or refractory cases. This review summarizes scientific articles about the etiology of, diagnostic tools for and treatment of the ocular manifestations of Behçet’s disease available in the PubMed database from 1 January 2016 to 1 May 2021. A multidisciplinary approach is necessary to effectively prevent permanent damage and thus improve the life quality of the patients. Therefore, it is crucial to raise awareness of the common clusters of symptoms, use of modern imaging methods, such as ocular computed tomography and fluorescein angiography, and novelty treatment algorithms to enable early diagnosis and appropriate management

MicroRNA Expression in Pseudoexfoliation Syndrome with the Use of Next-Generation Sequencing

Pseudoexfoliation syndrome (PEX) is a clinically important and biologically intriguing systemic disorder of the extracellular matrix. PEX etiopathogenesis was proved to be connected to multiple genes and other factors. However, the exact etiopathogenesis remains unknown. The aim of this study was to analyze miR expression in PEX using next-generation sequencing. An attempt was made to find the most commonly occurring miR in PEX, to evaluate miR that may have an essential role in the etiology of PEX syndrome. In addition, the correlation between the selected miRs’ expressions and age was investigated. Anterior lens capsules were obtained during cataract surgery. Next-generation sequencing was conducted on Illumina MiSeq. The average age was 68.2 years (with standard deviation +/− 6.92 years). Ten miRs with the highest level of expression represent approx. 95% of all readings. Four miRs with statistically significant differences in expression between groups have been distinguished: miR-671-3p, miR374a-5p, miR-1307-5p and miR-708-5p. The relationship between the most frequent miRs’ expressions and age has been evaluated and no correlation has been detected. In view of the above, it seems reasonable to examine the influence of miR on the biogenesis of PEX. Further studies on miR-671-3p, miR-374a-5p, miR-1307-5p and miR-708-5p expression in PEX are needed

The Importance of MicroRNA Expression in Pseudoexfoliation Syndrome

Pseudoexfoliation syndrome (PEX) is an important systemic disorder of the extracellular matrix, in which granular amyloid-like protein fibers accumulate in the anterior segment of the eyeball as well as in other organs. PEX is currently considered to be a multifactorial systemic disorder with genetic and environmental risk factors. The aim of this manuscript was to analyze miR expression in PEX. In recent years, an attempt has been made to investigate and describe the level of expression of selected miRs in PEX. Four polymorphisms of genes isolated from the blood that may be related to PEX were identified and miR-122-5p was found to be upregulated in patient blood. Furthermore, 18 miRs were identified with a statistically different expression in the aqueous humor. A significantly elevated expression of miR-125b was found in the anterior lens capsule, and four miRs were described, which may have a significant impact on the development of PEX. Regulatory miR molecules are gaining more and more importance in research aimed at identifying and isolating molecular markers related to the pathogenesis and prognosis of PEX, but further studies are needed

Selective Laser Trabeculoplasty in the Treatment of Ocular Hypertension and Open-Angle Glaucoma: Clinical Review

Selective laser trabeculoplasty (SLT) is a glaucoma treatment that reduces intraocular pressure (IOP). Its mechanism is based on the biological effects of the selective application of laser energy to pigmented trabecular meshwork (TM) cells, resulting in increased outflow facility. Herein, we review current publications on SLT and summarize its efficacy and safety for different indications in open-angle glaucoma (OAG) and ocular hypertension (OHT) treatment. SLT effectively reduces IOP when used as a primary treatment. In patients whose IOP is medically controlled, SLT helps to reduce medication use, and when maximally tolerated topical therapy is ineffective, SLT facilitates the realization of the target IOP. SLT is a repeatable procedure for which the vast majority of complications are mild and self-limiting. With effective IOP reduction, low complication rates and the potential to repeat the procedure, SLT offers the possibility of delaying the introduction of medical therapy and other more invasive treatment modalities while simultaneously avoiding the accompanying complications. With this knowledge, we suggest that SLT be considered as an essential primary treatment option in OAG and OHT, switching to other treatment modalities only when laser procedures are insufficient for achieving the required target IOP

Imbalance in PB IL-17-Secreting and Regulatory Cells in Pars Planitis Is Associated with Dysregulation of IFN-γ-Secreting Cells, Especially in Patients with Clinical Complications

Background/Purpose. Pars planitis (PP) is a chronic intermediate uveitis of undefined cause, although autoimmune etiology is strongly suggested. This study was undertaken to evaluate circulating pro- and anti-inflammatory lymphocyte subpopulations in patients with PP. A better understanding of immune alterations in PP may contribute to the development of an appropriate biologic treatment approach. Material and Methods. In our case-control study, samples of peripheral blood from 15 patients with pars planitis and 17 healthy subjects were collected. The patients underwent a full ophthalmological evaluation including macular optical coherence tomography (OCT) and submacular choroid (with enhanced deep imaging) with the SD-OCT Spectralis system. By flow cytometry, we assessed lymphocyte subpopulations as follows: Th1 subset: CD3+CD8-IFN-γ+ and CCR4-CXCR3+IFN-γ+ cells, Th17 subset: CD3+CD8-IL-17+ and CCR4+CCR6+IL-17+ cells, T regulatory (Treg): CD4+CD25hiCD127- cells, T suppressor (Tsup): CD8+CD28-FOXP3+ cells, and B regulatory (Breg): CD19+CD24hiCD38hi cells. The results are presented as the median percentage of immune cells in comparison to those obtained from the healthy control group. Results. In patients, an increase in the population of Th17-secreting cells negatively correlated with the abundance of both IFN-γ-producing and T regulatory as well as suppressor cells, regarding all the phenotypes studied. Although a strong dependence of the PB Th1 cell compartment on the duration of the disease was observed, it was limited to the subgroup of patients with macular edema only. The frequency of B regulatory cells was unchanged compared to controls. Conclusions. In pars planitis, the alterations in lymphocyte cell distribution affect primarily the T cell repertoire. The imbalance in PB Th1/Th17/Treg cells creates proinflammatory conditions, strengthening the suggestion that the immune background may play a role in pars planitis pathogenesis. Also, circulating Th1 level may be of potential clinical relevance in terms of prediction of a more severe course of the disease