Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

This paper provides the summaries on nine (9) important and clinically relevant publications in the field of uveitis. The first is on the standardization of uveitis nomenclature, more popularly known by its acronym - SUN, which was a result of an international workshop participated by uveitis experts in 2004. Five (5) papers were large, multicenter, clinical trials that demonstrated safety and efficacy of two (2) corticosteroids delivery devices (dexamethasone implant [Ozurdex] and fluocinolone acetonide implant [RetisertTM]) and one (1) immunomodulatory drug (adalimumab). The POINT trial compared various delivery approaches when using corticosteroids for the treatment of uveitic macular edema. The FAST trial compared two (2) durable and commonly-prescribed steroidsparing immunosuppressants, methotrexate and mycophenolate mofetil, for the treatment of non-infectious uveitis. Lastly, the SITE study, which was a large retrospective cohort study, determined the risks of overall and malignancy-related deaths among patients with inflammatory eye diseases receiving systemic immunosuppressants. Findings of these studies provide basis and rationale for the care and management of patients with uveitis and lay the groundwork for future research.
Uveitis ; Clinical Trial ; Review ; Adrenal Cortex Hormones

PURPOSE: We report a case of Urrets-Zavalia syndrome with a fixed dilated pupil after an uneventful trabeculectomy.CASE SUMMARY: Trabeculectomy was performed on a 51-year-old male who had a history of recurrent uveitis in the left eye, with uncontrolled intraocular pressure despite maximally-tolerated medial therapy. There was no unexpected event during surgery. Topical 1% atropine was used for only 2 days after surgery. In the early postoperative period, 1% prednisolone and 0.3% ofloxacin were given four times a day, then gradually reduced. One month later, only 1% prednisolone was given once a day. Intraocular pressure in his left eye was well controlled from 8–14 mmHg after surgery. One month after surgery, the pupils remained dilated. There was no reaction to topical 2% pilocarpine and no relative afferent pupillary defect or posterior synechia.CONCLUSIONS: Our case, although rare, suggests that Urrets-Zavalia syndrome should be considered in patients with well-controlled intraocular pressure after uneventful trabeculectomy.
Atropine ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Ofloxacin ; Pilocarpine ; Postoperative Period ; Prednisolone ; Pupil ; Pupil Disorders ; Trabeculectomy ; Uveitis

Behcet syndrome (BS) is a chronic systemic inflammatory disorder involving vessels of all sizes, characterized by relapsing episodes of oral and/or genital ulcers, as well as skin lesions. Ocular, vascular, gastrointestinal, neurological system involvement can cause significant morbidity and mortality. Glucocorticoids and immunosuppressants are the cornerstones for the management of BS. Biologic agents has been recommended for severe and/or refractory BS. Interferon-α (IFN-α) had multiple biological effects, such as antiviral and antiproliferative, that could regulate both innate and adaptive immunity in BS. Growing evidence showed the efficacy of IFN-α in severe and/or refractory BS. Many studies have demonstrated that IFN-α has comparable effectiveness and tolerance profiles as anti-tumor necrosis factor (TNF) agents for Behcet's uveitis with a much lower cost and steroid-and immunosuppressant-sparing effects. IFN-α has been recommended as second-line therapy for ocular involvement of BS in EULAR (The European League Against Rheumatism) 2018. IFN-α also improves mucocutaneous lesions in BS with the dosage from 3 to 9-12 million IU three times per week. A few cases indicated the therapeutic potential of IFN-α in intestinal BS. As a new trial of IFN-α in vascular BS (VBS), a recent study revealed the lower relapse rate and higher recanalization rate with IFN-α in lower extremity deep vein thrombosis (DVT). Another two case reports presented the efficacy of IFN-α in pulmonary artery involvement in BS. Also, case reports have shown successful treatment in refractory neurological involvement. There are two subtypes of IFN-α commonly used in autoimmune diseases, named IFN-α2a and IFN-α2b. IFN-α2a seemed more effective than IFN-α2b, especially in ocular and mucocutaneous involvement of BS. Side effects of IFN-α are dose-dependent and not severe. The most frequent side effects are flu-like syndrome, mild leukopenia and alopecia. Considering the potential risk of tuberculosis (TB) and hepatitis B virus (HBV) reactivation of TNF-α inhibitors, IFN-α is safe due to its anti-HBV effect and protective effect on TB. In conclusion, IFN-α is a promising choice for severe and/or refractory BS patients, especially for those who are intolerant or contraindicant to other biological agents, such as TNF inhibitors. Further prospective controlled studies are warranted to confirm the efficacy and safety of IFN-α in BS.
Behcet Syndrome/drug therapy* ; Glucocorticoids ; Humans ; Immunosuppressive Agents ; Uveitis ; Venous Thrombosis

PURPOSE: This study sought to describe the different clinical features and presentations of primary ocular toxoplasmosis in a setting not demonstrating an outbreak of disease.METHODS: This was a retrospective review of patients presenting to uveitis management services in Auckland and Hamilton, New Zealand between 2003 to 2018 with uveitis and positive toxoplasmosis immunoglobulin M serology.RESULTS: We identified 16 patients with primary acquired toxoplasmosis infection and ocular involvement. The mean age was 53 years. Systemic symptoms were reported in 56% (9 / 16). Visual acuity was reduced to 20 / 30 or less in 50% of patients (8 / 16). A single focus of retinitis without a pigmented scar was the salient clinical feature in 69% (11 / 16). Optic nerve inflammation was the sole clinical finding in 19% (3 / 16). Bilateral arterial vasculitis was the sole clinical finding in 13% (2 / 16). A delay in the diagnosis of toxoplasmosis of more than two weeks occurred in 38% (6 / 16) due to an initial alternative diagnosis. Antibiotic therapy was prescribed in all cases. Vision was maintained or improved in 69% (11 / 16) at the most recent follow-up visit (15 months to 10 years). Relapse occurred in 69% (11 / 16), typically within four years from the initial presentation.CONCLUSIONS: Primary ocular toxoplasmosis presenting in adulthood is a relatively uncommon cause of posterior uveitis in New Zealand. This condition should be considered in any patient presenting with retinitis or optic nerve inflammation without a retinochoroidal scar. This disease tends to relapse; thus, close follow-up is required.
Cicatrix ; Diagnosis ; Follow-Up Studies ; Humans ; Immunoglobulin M ; Inflammation ; New Zealand ; Optic Nerve ; Recurrence ; Retinitis ; Retrospective Studies ; Toxoplasmosis ; Toxoplasmosis, Ocular ; Uveitis ; Uveitis, Posterior ; Vasculitis ; Visual Acuity

In patients with inflammatory bowel disease (IBD), ocular extraintestinal manifestations (EIM) are less common than EIM of other systems, but they are clinically important because they can lead to complications that can cause catastrophic damage to the visual acuity and ocular structure. Anterior uveitis and episcleritis are the most common ocular EIM. Involvement of the orbit, posterior segment, and optic nerve can also occur. A variety of treatments are available ranging from topical steroids to systemic immunosuppressive therapies. The treatment of IBD is also essential if the activity of inflammatory bowel disease affects the ocular symptoms.
Colitis, Ulcerative ; Crohn Disease ; Humans ; Inflammatory Bowel Diseases ; Ophthalmology ; Optic Nerve ; Orbit ; Scleritis ; Steroids ; Uveitis ; Uveitis, Anterior ; Visual Acuity

OBJECTIVE: Acute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). However, the relationship between AAU and radiographic progression in axSpA remains unclear. Hence, we investigated whether the presence of AAU is associated with radiographic structural damage in patients with axSpA. METHODS: Clinical and radiographic data were obtained from 253 patients with axSpA. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Progression was defined as mSASSS worsening by ≥two units. Using propensity score (PS) matching, differences between patients with and without AAU were analyzed. RESULTS: The proportion of progressors among patients with AAU was lower than that of patients without AAU (13.6% vs. 29.5%, p=0.058). The rate of increase in mSASSS and number of syndesmophytes were lower in patients with AAU than patients without AAU (0.57±1.37 vs. 1.02±1.79, p=0.085 and 0.46±1.45 vs. 0.83±1.62, p=0.158). In multivariate regression analysis, presence of AAU was independently associated with slowed radiographic progression (odds ratio [95% confidence interval] 0.21 [0.07, 0.67], p=0.004). CONCLUSION: PS-matched axSpA patients with AAU showed significantly less radiographic progression than those without AAU.
Humans ; Propensity Score ; Spine ; Spondylitis, Ankylosing ; Uveitis ; Uveitis, Anterior

A 10-year-old intact female Jindo dog was presented with a 1-week history of conjunctival redness and ocular discharge in the left eye. There was an absence of menace response, dazzle reflex, and direct pupillary light reflex. Slit-lamp biomicroscopy revealed corneal edema, ciliary flush, and aqueous flare. Intraocular pressure was 68 mmHg. Based on the information available, a diagnosis of glaucoma and uveitis was made. Subsequent histopathologic examination showed the glaucoma was produced by the effects of goniodysgenesis, posterior synechia, and pigment dispersion in the trabecular meshwork. This is the first report of primary glaucoma caused by goniodysgenesis in Jindo dogs.
Animals ; Aqueous Humor ; Child ; Corneal Edema ; Diagnosis ; Dogs ; Female ; Glaucoma ; Humans ; Intraocular Pressure ; Reflex ; Trabecular Meshwork ; Uveitis

In patients with inflammatory bowel disease (IBD), ocular extraintestinal manifestations (EIM) are less common than EIM of other systems, but they are clinically important because they can lead to complications that can cause catastrophic damage to the visual acuity and ocular structure. Anterior uveitis and episcleritis are the most common ocular EIM. Involvement of the orbit, posterior segment, and optic nerve can also occur. A variety of treatments are available ranging from topical steroids to systemic immunosuppressive therapies. The treatment of IBD is also essential if the activity of inflammatory bowel disease affects the ocular symptoms.
Colitis, Ulcerative ; Crohn Disease ; Humans ; Inflammatory Bowel Diseases ; Ophthalmology ; Optic Nerve ; Orbit ; Scleritis ; Steroids ; Uveitis ; Uveitis, Anterior ; Visual Acuity

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis), which are the main treatment for ankylosing spondylitis (AS), have been reported not only to reduce the incidence of anterior uveitis (AU) but also to induce it, and these effects differ among the various types of TNFis in clinical use. The present study investigated the effect of TNFis on uveitis by analyzing the long-term clinical course of AU in AS patients treated with TNFi therapy. METHODS: Patients treated with at least one TNFi between January 2007 and July 2017 were reviewed, and 54 patients with at least one episode of AU were included in this study. The TNFis included anti-TNF-α antibodies (adalimumab, infliximab, and golimumab), and a soluble TNF receptor molecule (etanercept). The effect of prevention of AU, the likelihood of new-onset uveitis after the initiation of TNFi therapy, and the effects of drug switching and dose escalation were assessed. RESULTS: The first uveitis flare was observed before TNFi therapy in 39 patients and after TNFi therapy in 15 patients. Anti-TNF-α antibodies were more efficacious in decreasing the recurrence of AU than etanercept. Among patients in which uveitis first occurred after beginning TNFi therapy, patients on etanercept tended to first develop AU less than 1 year after starting the drug, and their AS tended to be well-controlled at the time of uveitis flares. Patients with a uveitis flare before their medication was switched did not recur afterwards, and five of eight patients showed no relapse after dose escalation. CONCLUSION: TNFis have various effects on AU. TNFis, particularly anti-TNF-α antibodies, should be considered in patients with AS and frequent AU relapse. Additionally, clinicians should consider whether AU is due to an absence of a therapeutic response of AS to TNFi treatment or to TNFi treatment itself, and appropriate treatment changes should be made accordingly.
Adalimumab ; Antibodies ; Drug Substitution ; Etanercept ; Humans ; Incidence ; Infliximab ; Receptors, Tumor Necrosis Factor ; Recurrence ; Spondylitis, Ankylosing ; Tumor Necrosis Factor-alpha ; Uveitis ; Uveitis, Anterior