Adolescent ; Child ; Humans ; Male ; Nephritis, Interstitial ; pathology ; Uveitis ; pathology

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.
Humans ; Immunosuppression ; methods ; Immunosuppressive Agents ; therapeutic use ; Uveitis ; immunology ; pathology ; therapy

Suprofen eye drop was instilled into one eye of 10 pigmented rabbits and then anterior uveitis was induced by intraperitoneal injection of endotoxin of Shigella flexneri serotype 1A to evaluate the effects of non-steroidal anti-inflammatory drug on endotoxin induced uveitis. The pupillary diameters were measured, and aqueous cell and flare gradings were recorded in 20 eyes of 10 rabbits for one week at an interval of 12 hours for the first 24 hours and then every 24 hours for a week. A difference between the treated and control groups were investigated. All the above parameters showed greatest changes at 12 or 24 hours after injection and became normal by one week. The two groups demonstrated statistically significant difference at 12 hours, day 1 and day 2 as for pupillary diameter, at day 1 and day 2 as for cell and at 12 hours and day 1 as for flare. Thus, it can be concluded that prostaglandins play a role in miosis, in the appearance of inflammatory cells and flare in endotoxin induced uveitis and the topical administration of non-steroidal anti-inflammatory drug can alleviate signs of anterior uveitis. Specific relationship between leukotriene B4 and aqueous cell was not demonstrated.
Administration, Topical ; Animals ; Cell Count ; Endotoxins ; Rabbits ; Shigella flexneri ; Suprofen/*therapeutic use ; Uveitis, Anterior/*drug therapy/pathology

A 60-year-old male was referred to the ophthalmologic clinic with aggravated anterior uveitis and corneal edema despite the use of topical and systemic steroids. He had undergone cataract surgery in both eyes 15 years previous. Slit lamp examinations revealed a retained lens fragment in the inferior angle of the anterior chamber, with severe corneal edema and mild anterior uveitis. The corneal edema and uveitis subsided following surgical extraction of the lens fragment. That a retained lens fragment caused symptomatic anterior uveitis with corneal edema 15 years after an uneventful cataract surgery is unique. A retained lens fragment should be considered as one of the causes of anterior uveitis in a pseudophakic patient.
Cataract Extraction/*adverse effects ; Corneal Edema/*etiology/*pathology ; Humans ; Lens, Crystalline/*pathology/surgery ; Male ; Middle Aged ; Postoperative Complications/pathology/surgery ; Pseudophakia/pathology ; Reoperation ; Severity of Illness Index ; Uveitis, Anterior/*etiology/*pathology

Inflammation of the uveal tract may be divided into three pathological types-acute purulent, subacute or chronic exudative, and granulomatous inflammations. However these catagories are considered merely as pathological types, not as clinical pictures. I. Acute purulent inflammations. Acute purulent inflammations, which are caused either by exogenous infection through a perforating wound or by endogenous infection through the blood-stream, tend usually to involve the entire globe. Such a generalized purulent inflammation of the inner eye is called panophthalmitis; it is not discussed here. II. Subacute and chronic exudative uveitis. Cases of subacute or chronic uveitis are much more common than those of acute panophthalmitis. The characteristics of such inflammations are essentially the same whatever their site. These may be summarized under three headings: changes in the affected tissue, the reaction of the pigmentary epithelium, and the formation of exudate. Whatever their etiology, the same general pathological picture is presented. In the initial stages there is vasodilation and edema with an intense and diffuse infiltration of the uveal tissues with mononuclear cells showing a tendency to aggregate into nodules. The inflammation may remain focal and involve some limited degree of necrosis whcih attracts large mononuclear phagocytes to be followed by repair by fibrosis. Such an inflammation may heal completely leaving a small and unimportant scar at the site of the focal lesion, or residual tell-tale aggregations of lymphocytes or mononuclear histiocytes to mark the site and extent of previous lesions. III. Granulomatous uveitis. The pure granulomatous reaction can be summarized as follows: at first an outpouring of leukocytes which are quickly replaced by a specific type of inflammatory cell-the large mononuclear phagocyte. These cells proliferate and invade the tissue. They undergo various transitions, chiefly into epitheloid cells. In many instance sensitizing antibodies are formed and the tissue become hypersensitive. Necrosis then occurs. Finally there it a reparative connective or glial tissue reaction with replacement of the destroyed tissue by a hyaline scar.
Antibodies ; Cicatrix ; Edema ; Epithelium ; Exudates and Transudates ; Fibrosis ; Head ; Histiocytes ; Hyalin ; Inflammation ; Leukocytes ; Lymphocytes ; Necrosis ; Panophthalmitis ; Pathology* ; Phagocytes ; Uveitis* ; Vasodilation ; Wounds and Injuries

PURPOSE: We describe the occurrence of a massive retinal hemorrhage following anterior chamber paracentesis in uveitic glaucoma. METHODS: A 33-year-old man who suffered from uveitic glaucoma was transferred to our hospital. The IOP in both his eyes was documented to vary between 11 mmHg and 43 mmHg and remained at a continuously high level for 7 months despite maximally tolerable medical treatment. A paracentesis was performed bilaterally to lower the IOP. RESULTS: Immediately after the paracentesis, massive retinal hemorrhages occurred in the left eye. Multiple round blot retinal hemorrhages with white centers occurred in the equator and peripheral retina, and small slit hemorrhages were observed in the peripapillary area. A fluorescence angiography(FAG) showed no obstruction of retinal vessels but a slightly delayed arteriovenous time in the left eye. CONCLUSIONS: It is important to be aware that patients who have a persistent relatively high IOP are at an increased risk of developing decompression retinopathy due to paracentesis and filtering surgery.
Uveitis, Anterior/*surgery ; Retinal Hemorrhage/*etiology/pathology ; Paracentesis/*adverse effects ; Male ; Intraocular Pressure ; Humans ; Glaucoma/*surgery ; Fundus Oculi ; Follow-Up Studies ; Fluorescein Angiography ; Anterior Chamber/*surgery ; Adult

PURPOSE: Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) METHODS: EIU was induced in female Lewis rats by single footpad injections of 200 microgram of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients. RESULTS: Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region. CONCLUSIONS: TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.
Animals ; Disease Progression ; Enzyme Inhibitors/*therapeutic use ; Female ; GTP-Binding Proteins/*antagonists & inhibitors/*metabolism ; Lipopolysaccharides ; Rats ; Rats, Inbred Lew ; Transglutaminases/*antagonists & inhibitors/*metabolism ; Uveitis/chemically induced/*enzymology/pathology

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

The authors wish to report a case of bilateral acute anterior uveitis and optic disc edema following a hemotoxic snake bite, in order to highlight the concomitant occurrence of these conditions and the potential adverse effects of anti-snake venom (ASV). A 35-year-old male was bitten by a viper at seventeen thirty hours, and was started on ASV. Two days following treatment he experienced sudden onset redness and painful diminution of vision in both eyes (OU). On examination, the patient's visual acuity (VA) in OU was 20/200. Examination revealed fresh keratic precipitates, cells, and flare in the anterior chamber (AC), posterior synechiae, sluggish and ill-sustained pupillary reaction, and hyperemic, edematous disc with blurred margins in OU. He was started on topical steroids, cycloplegics and intravenous methylprednisolone. Following treatment, the patient showed improvement and was continued on topical medications and oral prednisolone tapered over 3 weeks, after which VA OU improved, the AC showed no cells and flare and disc edema resolved. Uveitis and optic disc edema in snake bite can either be due to the direct toxic effects of the venom or the effect of ASV. Steroids have a beneficial role in the management of these symptoms.
Acute Disease ; Adult ; Antivenins/*adverse effects ; Glucocorticoids/administration & dosage ; Humans ; Hyperemia/drug therapy/etiology/pathology ; Male ; Methylprednisolone/administration & dosage ; Papilledema/drug therapy/*etiology/pathology ; Snake Bites/*complications/*therapy ; Uveitis, Anterior/drug therapy/*etiology/pathology

We report a case of recurrent occlusion of laser iridotomy (LI) sites after a Visian ICL (Implantable contact lens version 4, Staar Surgical AG, Nidau, Switzerland) implantation. A 45-year-old woman had bilateral ICL implantation after placement of two peripheral LI sites in each eye to prevent pupillary block. At one month after the operation, severe narrowing or occlusion of four LI sites occurred. After this, although she received four additional LIs at postoperative months 1, 6, 9 and 10 in both eyes, the narrowing or occlusion recurred. Mild chronic anterior chamber inflammation was observed intermittently throughout the follow-up period. We performed clear lens extraction in both eyes (at postoperative month 11 in the left eye and month 26 in the right eye) due to recurrent occlusion of the LI sites and excess trabecular meshwork pigment deposition presumably caused by the four repeated LIs. Recurrent obstruction of LI sites can occur after ICL implantation. These problems were unresolvable despite four repeated laser iridotomies. The risks associated with anterior uveitis must be considered when planning an ICL implantation.
Female ; Humans ; Iridectomy/*methods ; Iris/*surgery ; *Laser Therapy ; Lasers, Solid-State ; Lens Implantation, Intraocular/*adverse effects ; Middle Aged ; *Phakic Intraocular Lenses ; Pigment Epithelium of Eye/pathology ; *Postoperative Complications ; Recurrence ; Reoperation ; Trabecular Meshwork/pathology ; Uveitis, Anterior/etiology