The impact of polymerase chain reaction (PCR) on diagnosis and management of infectious uveitis at a tertiary care facility

Background Polymerase Chain Reaction (PCR) is a well-accepted adjunct in the management of infectious uveitis. In turn, few reports in the literature have evaluated how PCR then impacts patient care. This study aims to evaluate the impact of PCR sampling on diagnosis and treatment of infectious uveitidies at a large tertiary care facility. Main body This is a retrospective, observational study of patients with aqueous and vitreous PCR samples obtained from 2014 to 2019. The study was undertaken at a single institution. At least one follow up visit following results of PCR testing was required for inclusion. If a patient had multiple PCR samples taken, only the first sample was included. The patients were divided into three categories based on pre-sampling diagnosis. A chi-square test was used to analyze the data. 108 cases were available for analysis. PCR did not change diagnosis or management in any of the cases where pre-sampling diagnosis carried a high clinical suspicion for negative PCR. Overall, the results of PCR testing had a more significant impact on diagnosis in those cases where pre-sampling diagnosis was unknown versus those where it was confirmatory in nature, thus presumed to be related to an infectious entity tested by PCR (74% vs. 29%, p = 0.00006). The rate of treatment change based on PCR was similar between those cases where there was a high clinical suspicion for positive PCR and those where pre-sampling diagnosis was unknown (32% vs. 33%, p = 0.95). Further analyzing specimens separately depending on source of sample, this pattern persisted for aqueous samples, with PCR showing a more significant impact on diagnosis in those cases where the diagnosis was unknown versus those where sampling was confirmatory (86% vs. 31%, p = 0.00004). The rate of change in treatment between the two groups was similar (35% vs. 31%, p = 0.79). Vitreous samples followed a similar pattern with a higher rate of diagnosis change for those cases where pre-sampling diagnosis was unknown and a similar rate in treatment change between the two groups, however this did not reach statistical signifigance (44% vs. 25%, p = 0.28; 27% vs. 33%, p = 0.74). Conclusion There is no well-defined algorithm as to when to employ PCR testing in uveitis. As expected, in our experience, it has the largest impact on diagnosis when the diagnosis is unknown, however even when confirmatory in nature, it continues to impact patient management.

Adhesion Molecule Targeted Therapy for Non-Infectious Uveitis

Non-infectious uveitis (NIU) is an inflammatory eye disease initiated via CD4+ T-cell activation and transmigration, resulting in focal retinal tissue damage and visual acuity disturbance. Cell adhesion molecules (CAMs) are activated during the inflammatory process to facilitate the leukocyte recruitment cascade. Our review focused on CAM-targeted therapies in experimental autoimmune uveitis (EAU) and NIU. We concluded that CAM-based therapies have demonstrated benefits for controlling EAU severity with decreases in immune cell migration, especially via ICAM-1/LFA-1 and VCAM-1/VLA-4 (integrin) pathways. P-selectin and E-selectin are more involved specifically in uveitis related to vasculitis. These therapies have potential clinical applications for the development of a more personalized and specific treatment. Localized therapies are the future direction to avoid serious systemic side effects.

Methotrexate Effectively Controls Ocular Inflammation in Japanese Patients With Non-infectious Uveitis

This single-center retrospective study investigated the clinical characteristics and efficacy of methotrexate (MTX) for the treatment of non-infectious uveitis for more than 6 months at Hiroshima University, from February 2016 to May 2021. Outcome variables included changes in systemic immunosuppressive treatment and intraocular inflammation. Out of 448 patients with non-infectious uveitis, 35 patients (14 male patients and 21 female patients; 65 eyes) treated with MTX for more than 6 months were analyzed. There were 15 patients with anterior uveitis and 20 with posterior and panuveitis. The mean dose of systemic corticosteroids decreased from 12.1 mg/day at baseline to 1.3 mg/day at 6 months and 0.6 mg at 12 months after starting MTX, and approximately 90% of patients were corticosteroid-free at 12 months. The percentage of eyes with inactive uveitis at 6, 12, and 24 months was 49.2%, 59.6%, and 90.0%, respectively. Mean relapse rate score also significantly decreased from 2.88 at baseline to 0.85 at 12 months (p < 0.001). Inflammatory control was achieved with MTX doses of 8–16 mg/week, with a median dose of 12 mg/week. Adverse effects of MTX were observed in 34.3% of patients, and 11.4% required discontinuation; most commonly hepatotoxicity (58.3%), followed by fatigue (25.0%), and hair loss (16.7%). No significant differences were found between the survival curves of patients with anterior uveitis and posterior/panuveitis (Wilcoxon rank-sum test). The percentage of eyes without IOP-lowering eye drops was significantly higher in patients with posterior/panuveitis at 24 months (p = 0.001). Our study suggests that MTX is effective in controlling ocular inflammation for Japanese patients with non-infectious uveitis. Relatively high incidence of MTX-related adverse effects in the Japanese population indicates that careful monitoring and dose adjustments are crucial for the long-term use of this therapy.

Anti-TNF-alpha-induced lupus in patients with non-infectious uveitis

Purpose Anti-TNF-α-induced lupus (ATIL) is a rare condition considered as a drug-induced lupus (DIL) in patients under anti-TNF-α therapies. Nowadays it is still unclear if ATIL is a classical DIL or represent a distinct syndrome. Some characteristics of DIL have been described specifically associated with patients with lupus-like syndrome receiving anti-TNF-α therapy: the severity of the disease, incidence/prevalence of dsDNA antibodies (anti-dsDNA) and hypocomplementaemia. The objective of this study is to describe the development of ATIL in patients with non-infectious uveitis in a single tertiary center. Methods Retrospective description of a case series. Results We describe three patients with noninfectious uveitis (NIU) of different etiologies who developed antinuclear antibody (ANA) and anti-dsDNA antibody positivity, arthritis and, in one case, skin lesions under adalimumab treatment. The condition resolved in all of them after adalimumab withdrawal. Corticosteroids were required in one patient, non-steroidal anti-inflammatory drugs in two patients, and hydroxychloroquine in one of them. None required another immunosuppressive drug. A subsequent control of the NIU could continue to be carried out without anti-TNF-α therapy in two patients and in the remaining a switch was made to another anti-TNF-α (golimumab). Conclusion The current report describes three cases of ATIL in patients with different types of NIU which share some common features: ANA positivity, articular symptoms, and a temporal relationship between symptoms onset and anti-TNF-α treatment. A review of the literature and comparison with the few previous reported ATIL cases was conducted as well.

Healthcare costs among patients with macular oedema associated with non-infectious uveitis: a US commercial payer’s perspective

ObjectiveTo describe patient characteristics and healthcare costs associated with uveitic macular oedema (UME) in US clinical practices from a commercial payer’s perspective.Methods and analysisThe IBM MarketScan Commercial Subset (1 October 2015–31 March 2020) was used to identify patients with non-infectious uveitis (NIU), with or without UME. Patients with UME at any time were further classified into subgroups of patients who received a UME diagnosis during the study period and those who received a UME diagnosis and local steroid injection (LSI) during the study period. Demographic and clinical characteristics, NIU-related treatments and healthcare costs were described for each cohort and subgroup during the most recent 12 months of continuous health plan enrolment. Healthcare costs were also described by vision status among all patients with NIU.ResultsA total of 36 322 patients with NIU were identified, of whom 3 301 (9.1%) had UME and 33 021 (90.9%) had no UME. Patients with UME more frequently received NIU-related treatment compared with those without UME (64.6% vs 45.0%), particularly LSI treatment (12.5% vs 0.7%). Mean total all-cause healthcare costs per-patient-per-year (PPPY) were higher among patients with UME ($19 851) than patients without UME ($16 188) and were especially high among those with bilateral UME ($24 162). Further, vision loss was more commonly observed in those with UME versus those without UME (5.7% vs 2.2%) and a trend of increasing healthcare costs with increasing vision loss was observed.ConclusionNIU is associated with substantial clinical and economic burden, particularly when UME is present.

Das Treatment Exit Options for Uveitis (TOFU) Register: Einbindung von Patienten in die Evidenzgenerierung

ZusammenfassungUveitis ist eine seltenere entzündliche Augenerkrankung, die zu schwerer Sehbehinderung und Blindheit führen kann und besonders Menschen im berufstätigen Alter betrifft. Besonders schwere Verläufe, die meist einer immunmodulierenden Therapie (IMT) bedürfen, treten bei einer Uveitis auf, die die hinteren Teile des Auges oder das ganze Auge betreffen und nicht infektiöser Ursache sind. Für diese Formen der Erkrankung gibt es nur wenig gute Evidenz zum langfristigen Management der Erkrankung und insbesondere zur Beendigung oder Reduktion einer IMT. Das Treatment exit Options For non-infectious Uveitis (TOFU) Register der Sektion Uveitis der Deutschen Ophthalmologischen Gesellschaft (DOG) hat das Ziel, Krankheitsverläufe von Patienten mit nicht-infektiöser nicht-anteriorer Uveitis zu dokumentieren und Empfehlungen zur Beendigung einer IMT zu erarbeiten. Ein wesentlicher Aspekt des TOFU-Registers ist die aktive Einbeziehung von Patienten in die Erfassung Patienten-berichteter Endpunkte über ein Patientenmodul (Patient Reported Outcomes, PROs). Neben seh- und gesundheitsbezogener Lebensqualität werden auch Fragebögen zur Therapieadhärenz, Produktivität und Auswirkungen der Therapien eingesetzt. Die eingesetzten Fragebögen wurden in dieser Kombination in einer Pilotstudie mit Patienten getestet und es hat sich gezeigt, dass die wesentlichen Patienten-relevanten Aspekte der Erkrankung und deren Auswirkungen auf den Alltag erfasst werden. Das Patientenmodul, wie das Register selbst, nutzt zur Dokumentation die electronic data capture (EDC)-Software REDCap (Version 9, Vanderbilt University, USA). Durch die Einbindung von Patienten in sowohl die Konzeption des Registers als auch die fortlaufende Datensammlung wird sichergestellt, dass Patienten-relevante Evidenz für z. B. die Erstellung von Leitlinien und Behandlungsempfehlungen generiert wird.