Chronic Endogenous Uveitis Research Articles

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Treat to Target in the Management of Chronic Uveitis

Uveitis is a cause of visual loss in 10% of the visually handicapped. The etiology of uveitis remains unknown in about 50% of cases. The most important diseases behind endogenous uveitis are spondyloarthropathies, juvenile idiopathic arthritis (JIA), sarcoidosis, multiple sclerosis, and tubulointerstitial nephritis. Uveitis may be caused by infectious agents such as toxoplasma, herpes viruses, Borrelia burgdorferi , cytomegaloviruses, tuberculosis, and syphilis. If the etiology is known, the treatment strategy is according to the underlying disease1,2,3. The treatment of chronic endogenous uveitis … Address correspondence to Dr. Kotaniemi. E-mail: kaisumkotaniemi{at}gmail.com

25-gauge Vitrectomy for Complicated Chronic Endogenous/Autoimmune Uveitis: Predictors of Outcomes

Purpose: To describe the course of inflammation and identify predictors of successful outcome in chronic endogenous/autoimmune uveitic patients following 25-gauge vitrectomy.Methods: In this retrospective study, charts of 74 patients (74 eyes) undergoing vitrectomy for complicated uveitis that had a minimum of 12 months follow-up were reviewed. Successful outcome measures were improvement (≥0.3 logMAR) of visual acuity (VA), decreased inflammatory activity (≥1+), and reduction of required drugs (more than one). Logistic regression techniques were used to identify predictors of successful outcomes.Result: A total of 44 (59%) of the 74 patients showed VA improvement, 38 (51%) showed decreased inflammatory activity, and 30 (40%) required fewer drugs following vitrectomy. Independent predictor for VA improvements was accompanying cataract extraction, for postoperative inflammatory decrease was the absence of preoperative cystoid macular edema and greater preoperative activity of inflammation, and for the reduction in the number of required drugs was preoperative presence of epiretinal membrane formation.Conclusion: 25-gauge vitrectomy may be beneficial in patients with complicated chronic endogenous uveitis in terms of VA and control of inflammation. Accompanying cataract extraction, when necessitated, during vitrectomy and the absence of preoperative cystoid macular edema were indicators of better outcomes. Establishing predictors may assist clinicians in better patient selection.

Comparison Between Intravitreal and Orbital Floor Triamcinolone Acetonide After Phacoemulsification in Patients With Endogenous Uveitis

To compare the effect of intravitreal and orbital floor triamcinolone acetonide (TA) on macular edema, visual outcome, and course of postoperative inflammation after cataract surgery in uveitis patients. Prospective, randomized clinical trial. Monocenter study (40 patients) with chronic endogenous uveitis who underwent phacoemulsification with intraocular lens implantation with either 4 mg intravitreal TA (n = 20) or 40 mg orbital floor TA (n = 20). The primary outcome was influence on cystoid macular edema (CME). Secondary outcome measures were best-corrected visual acuity (BCVA), anterior chamber cell grade, laser flare photometry, giant cell deposition, posterior capsule opacification (PCO), and intraocular pressure. Mean central foveal thickness decreased in the intravitreal TA group and increased in the orbital floor TA group (P < .001 at one and three months). CME improved in 50% of patients after intravitreal TA, whereas it was unchanged after orbital floor TA (difference between the groups at three months, P = .049). Mean BCVA (logarithm of the minimal angle of resolution) improved postoperatively (P < .001) from 0.76 and 0.74 to 0.22 and 0.23 in the intravitreal TA and orbital floor TA group, respectively. Anterior chamber cell count at one month was lower in the intravitreal TA than in the orbital floor TA group (P = .02). Laser flare photometry values and giant cell numbers were slightly higher after orbital floor TA than after intravitreal TA. The groups did not differ with respect to PCO rate and ocular hypertension. The CME improvement and anti-inflammatory effect after intravitreal TA was better than after orbital floor TA injection in cataract surgery in uveitis patients.

Zur Behandlungsstrategie bei chronischer endogener Uveitis

The treatment of chronic endogenous uveitis has included the use of local and systemic corticosteroids since the early 1950 s, and these still constitute the first-line option in the treatment, once an infectious aetiology has been excluded. Since the 1960 s, broad experience has been collected with antiproliferative and alkylating agents, and since the 1980 s several immunosuppressants have been employed in the therapy for endogenous uveitis. It has been recognised that the therapeutic response is not only related to a specific uveitic entity, but also to the genetic background of the individual. Therefore, no clear guide lines for therapy exist and, for most of the drugs, controlled studies are not available. Vitrectomy and intravitreal drug delivery have been added as local options on top or in case of failure of systemic therapies. The advent of biological agents, however, i. e. the introduction of interferon alpha and TNF alpha blocking agents, has opened a new era in the treatment of immunogenetic and autoimmune disorders. Evidence-based knowledge and personal experience have been reviewed to provide an update on the therapeutic strategy for chronic endogenous uveitis. The newly introduced biologicals seem to represent an interesting addition to the existing therapeutic options. Informations pertaining to efficacy and side effects of a long-term treatment of uveitis are, nevertheless, as yet not available.

The Diagnostic Yield of Vitrectomy Specimen Analysis in Chronic Idiopathic Endogenous Uveitis

The low diagnostic yield of vitrectomy specimen analysis in chronic idiopathic uveitis (CIU) has been related to the complex nature of the underlying disease and to methodologic and tissue immanent factors in older studies. In an attempt to evaluate the impact of recently acquired analytic methods, the authors assessed the current diagnostic yield in CIU. Retrospective analysis of consecutive vitrectomy specimens from patients with chronic endogenous uveitis (n = 56) in whom extensive systemic workup had not revealed a specific diagnosis (idiopathic) and medical treatment had not resulted in a satisfying clinical situation. Patients with acute postoperative endophthalmitis served a basis for methodologic comparison (Group 2; n = 21). In CIU, a specific diagnosis provided in 17.9% and a specific diagnosis excluded in 21.4%. In 60.7% the laboratory investigations were inconclusive. In postoperative endophthalmitis, microbiological culture established the infectious agent in 47.6%. In six of eight randomly selected cases, eubacterial PCR identified bacterial DNA confirming the culture results in three, remaining negative in two with a positive culture and being positive in three no growth specimens. A double negative result never occurred, suggesting a very high detection rate, when both tests were applied. The diagnostic yield of vitrectomy specimen analysis has not been improved by currently routinely applied methods in recent years in contrast to the significantly improved sensitivity of combined standardized culture and PCR analysis in endophthalmitis. Consequently, the low diagnostic yield in CIU has to be attributed to insufficient understanding of the underlying pathophysiologic mechanisms.

Low-dose Cyclosporin A Therapy in Treating Chronic, Noninfectious Uveitis

To describe the authors' approach to the management of patients with recalcitrant, chronic, endogenous uveitis using low-dose Cyclosporin A (CSA) alone or in combination with other immunosuppressive agents with attention to the anti-inflammatory efficacy, visual outcome, and side effects of therapy. The authors reviewed the records of 50 patients (92 eyes) with uveitis of various etiologies who had been treated with low-dose CSA (2.5-5.0 mg/kg daily) alone or in combination with prednisone and/or azathioprine (1.5-2.0 mg/kg daily). The median follow-up on low-dose CSA was 16 months (range, 6-64 months). Inflammatory control was achieved in 68 (73.9%) eyes, while persistent inflammatory activity was observed in 14 (15.2%). Thirty-eight (41%) eyes improved two Snellen lines or more, 43 (47.0%) stabilized, and 11 (12.0%) lost two lines or more. The CSA was discontinued because of nephrotoxicity in three patients and in each of two with systemic hypertension and constitutional intolerance to the drug, respectively. Thirteen patients enjoy inflammatory remission with this regimen. Low-dose CSA used alone or in combination with other immunosuppressive agents is effective in achieving inflammatory control with a favorable visual outcome and provides a useful steroid-sparing strategy in the management of chronic endogenous uveitis. The CSA-associated toxicity may be reduced by initiating therapy at very low initial doses, with incremental dosage escalation to the desired target range.

Mouse exophthalmic chronic orbital inflammatory disease. Induction by human leucocyte intracellular Mollicutes.

Mollicutes are cell wall deficient bacteria which may be overlooked or confused with viruses because of indistinct light microscopic morphology, poor staining, difficulty in cultivation, and the ability to pass 0.450 micron filters. As they have a distinctive ultrastructural appearance they can be identified using transmission electron microscopy [TEM]. Using TEM vitreous leucocytes from chronic endogenous uveitis patients may demonstrate non-cultivable intracellular 0.005-1.0 micron mollicute-like organisms [MLO], some of which develop into distinctive cell walled cocci, 0.5-0.7 micron in diameter. Inoculation of those MLO containing human vitreous into mouse eyelids produces chronic cardiac and uveal vasculitis with orbital inflammation. Similar MLO are found within the mouse lesional leucocytes. This report describes the chronic orbital inflammation with vasculitis in 67 of 100 of those MLO inoculated mice versus 0 of 200 controls (P less than 0.05). Exophthalmos with inflammation also occurred in 12 of those 67 mice (P less than 0.05). MLO were found within orbital lesional leucocytes of 10 of 10 of those mice using a TEM versus 0 of 10 controls. The results indicate that vasculitis and exophthalmos were important features of this MLO induced mouse orbital inflammation. The implication of these results for human idiopathic chronic orbital inflammatory disease is discussed.

Pars plana vitrectomy in chronic uveitis

Sixty-eight patients (74 eyes) with chronic endogenous uveitis underwent pars plana vitrectomy. An increase in visual acuity was observed in 70% postoperatively. Visual results basically depended on the extent of previous damage to the macula. A lensectomy-vitrectomy was done in 23 eyes, while 51 eyes underwent merely a pars plana vitrectomy. The frequency and severity of uveitic relapses were diminished in virtually all cases.