Recurrent and chronic anterior uveitis: Long-term outcome and treatment strategies.

PURPOSE: To study the long-term clinical outcome and treatment strategies of recurrent and chronic non-infectious anterior uveitis. METHODS: Multicenter study of anterior uveitis patients from 2001 to 2022. Outcome measures included ocular complications, medical and surgical therapies, and visual acuity measured at the beginning of follow-up and at 1, 2, and 5 years thereafter. RESULTS: In total, 76 patients were included, with a mean follow-up of 6.8 years. Idiopathic anterior uveitis was the most common etiology (56%). Immunomodulatory agents (IMAs) were used in almost half of the cohort. Early initiation of IMAs was associated with a lower risk of developing glaucoma ( P = 0.019). Mean best corrected visual acuity (BCVA) improved after 5 years in both groups. Early use of immunomodulation was correlated with a better visual outcome at 2 years ( P = 0.024). CONCLUSION: Chronic and recurrent anterior uveitis were associated with greater risk than expected for ocular complications, surgeries, and vision impairment. Early initiation of immunomodulation should be strongly considered to improve clinical course and outcome.

Retinal Diseases: The Next Frontier in Pharmacodelivery.

The future continuous growth of the global older population augments the burden of retinal diseases worldwide. Retinal characteristics isolating and protecting the sensitive neuro-retina from the rest of the ocular tissues challenge drug delivery and promote research and development toward new horizons. In this review, we wish to describe the unmet medical needs, discuss the novel modes of delivery, and disclose to the reader a spectrum of older-to-novel drug delivery technologies, innovations, and the frontier of pharmacodelivery to the retina. Treating the main retinal diseases in the everlasting war against blindness and its associated morbidity has been growing steadily over the last two decades. Implants, new angiogenesis inhibitor agents, micro- and nano-carriers, and the anchored port delivery system are becoming new tools in this war. The revolution and evolution of new delivery methods might be just a few steps ahead, yet its assimilation in our daily clinical work may take time, due to medical, economical, and regulatory elements that need to be met in order to allow successful development and market utilization of new technologies. Therefore, further work is warranted, as detailed in this Pharmaceutics Special Issue.

Tarsier Anterior Chamber Cell Grading: Improving the SUN Grading Scheme with a Visual Analog Scale.

PURPOSE: To compare an analog visual scale in grading anterior chamber cells (ACC) to a modified Standardization of Uveitis Nomenclature (SUN) ACC scale. METHOD: A graphical representation of anterior chamber cells as a reference and a test set was created and shown to two groups of experienced uveitis experts. Group 1 was given the analog scale in written format, while group two was given the reference images for comparison. Each test subject was asked to provide the best approximation for each grade. RESULTS: Eleven graders participated in phase 1. Correct grading occurred in 87.4% of cases. Discrepancies were seen at all grades. Only 3 of 11 graders were able to achieve a perfect score. Seven graders participated in phase 2. Agreement was 95.2% with 4/7 graders achieving a perfect score. Discrepancies were seen at higher grades only. CONCLUSIONS: ACC grading is improved by a visual grading scale, and interobserver variability is reduced.

ISOPT Clinical Hot Topic Panel Discussion on Uveitis and Inflammation.

For this "hot topic" session in uveitis we selected first and foremost an issue that puts our clinical work and research in "holding pattern." The issue is our method of evaluating the severity of uveitis. We posed the following questions to our esteemed panelists: 1.The relative significance of cells vs. flare in following uveitis patients 2.Cells/flare measurements 3.A glance into the future and the relevance of endpoints in clinical studies and their methodologies While there are different opinions in managing and monitoring uveitis patients, there seems to be an agreement on the high need of improving objective mode/s of reliably measuring both cells and flare and better understand their significance.

ISOPT Clinical Hot Topic Panel Discussion on Medical Treatment of Retinal Diseases.

Topics change as time flows. This is especially true in retinal therapeutics that merely 25 years ago was mainly a surgical field and in two decades has been transformed into a classic pharmacologic medical field. That said, the classic questions of pharmacology such as pharmacokinetics, pharmacodynamics, dosing and delivery systems currently engage most retina specialists. It was therefore easy for us to focus the 2018 ISOPT Clinical retinal discussions on delivery systems, drug efficacy and classic questions such as: have we reached the unbreakable glass ceiling of efficacy in wet age-related macular degeneration (AMD)? Can we aim our target to achieve an even higher effect? Can it be reached by new chemical/biological entities or would delivery system allow us to reach higher points of efficacy? The discussion also addressed the issue of dry AMD and the glorious parade of failures so far, and how do we measure success and failure via relevant endpoints.

The gap between the need for novel retinal drug delivery methods, technologies in R&D phase, and approved ocular drug delivery technologies.

The past four decades were marked by the realization that the delivery of drugs into the eye is a crucial step in the development and utilization of new ocular drugs. This realization led to vast efforts and investments in research and development (R&D) to improve and approve new technologies. The realization of intravitreal injections and the vast utilization of this methodology in retinal disease management deepened the need for new drug delivery methods for drugs already approved safe and effective. Yet, there are only a handful of technologies approved and in clinical use today. Here, we focus on this gap by highlighting bottlenecks and by encouraging creative thinking for solutions.

[IDIOPATHIC RETINAL VASCULITIS - THE INTERPLAY BETWEEN A CHRONIC IDIOPATHIC OCULAR DISEASE, ITS THERAPY AND THE PATIENT].

INTRODUCTION: This is an article on a six year follow-up of a patient diagnosed with idiopathic retinal vasculitis. Her medical history, symptoms and findings are presented in detail, related to the diagnostic investigations and the resulting diagnosis. Patient follow-up was marked with repeated attempts to utilize steroid sparing strategies including antimetabolites such as Methotrexate and mycophenolate Mofetyl with only limited success. Biologic agent (anti TNF), Adalimumab, was also not successful. We discuss the difficulties experienced by the patient and her response to our inability to completely control her symptoms. On another level, we relate to our own difficulties to assess her response to therapy given her preserved vision on the one hand and her apparent uncontrolled retinal vascular leakage. The patient's ability to function in daily life reduces her willingness to endure therapy-related adverse events.

Herpetic Anterior Uveitis - Analysis of Presumed and PCR Proven Cases.

PURPOSE: To describe the demographics and clinical characteristics of patients with herpetic anterior uveitis (HAU), and compare characteristics by pathogen, recurrence, and association to iris atrophy. METHODS: Multicenter, retrospective study of AU patients diagnosed clinically and by polymerase chain reaction (PCR). RESULTS: The study included 112 eyes in 109 patients: 54 (48.2%) HSV, 34 (30.4%) VZV, 2 (1.8%) CMV, and 22 (19.6%) unspecified diagnosis. HSV eyes, compared to VZV, had a higher recurrence rate, corneal involvement, KPs, iris atrophy, elevated IOP and posterior synechia (p < 0.05). VZV patients had more frequent immunomodulatory treatments and history of systemic herpetic disease (p < 0.05). Fifty-nine (52.7%) eyes had recurrent disease. Iris atrophy was associated with a higher prevalence of posterior synechia, dilated distorted pupil, and high IOP (p < 0.05). CONCLUSION: Different HAU-causing Herpesviridae produce common clinical findings; therefore, PCR should be used more often to confirm specific diagnosis. Iris atrophy was associated with more severe disease.

The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

PURPOSE: This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. METHODS: This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. RESULTS: The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. CONCLUSIONS: Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.

Intraocular inflammation in autoimmune diseases.

BACKGROUND: The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). OBJECTIVES: To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. METHODS: We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." RESULTS: An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. CONCLUSION: An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis.

PURPOSE: To evaluate the clinical experience with methotrexate as a first-line corticosteroid-sparing drug in patients with resistant ocular inflammation. METHODS: We retrospectively studied 39 consecutive patients with uveitis (n = 36) or scleritis (n = 3) who were treated with methotrexate following inadequate control with corticosteroids lasting five years. Criteria for initiating treatment with methotrexate and defining outcome were strictly defined. RESULTS: The cohort included 21 females and 18 males, all Caucasians, with a mean age of 26.6 years (range: 3-73 years). Patients were followed up for 21.5 +/- 12.6 months. Treatment was discontinued due to side effects in 10 patients (26%). Of the remaining 29 patients, full or partial control of inflammation was achieved in 23 (79%). Response to treatment was observed after a mean of 2.4 +/- 0.8 months. Ten patients were fully controlled and discontinued methotrexate therapy after a mean of 20.9 +/- 9.2 months, with no recurrence of inflammation. Use of topical and systemic corticosteroids was markedly reduced in responsive patients. CONCLUSIONS: Methotrexate is recommended as a first-line adjunct to or replacement of systemic corticosteroids in the treatment of ocular inflammation.