Comparison of infliximab with adalimumab for the treatment of non-infectious uveitis: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). METHODS: We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated. RESULTS: Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab. CONCLUSION: Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.

Interleukin-6 and Macular Edema: A Review of Outcomes with Inhibition.

This paper describes the current literature on the molecular pathophysiology of interleukin-6 (IL-6) in the genesis of macular edema and on the outcomes with IL-6 inhibitors in the treatment of non-infectious macular edema. The role of IL-6 in the development of macular edema has been well elucidated. IL-6 is produced by multiple cells of the innate immune system and leads to a higher likelihood of developing autoimmune inflammatory diseases, such as non-infectious uveitis, through a variety of mechanisms. These include increasing the helper T-cell population over the regulatory T-cell population and leading to the increased expression of inflammatory cytokines, such as tumor necrosis factor-alpha. In addition to being key in the generation of uveitis and subsequent macular edema through these inflammatory pathways, IL-6 also can lead to the development of macular edema through other pathways. IL-6 induces the production of vascular endothelial growth factor (VEGF) and facilitates vascular leakage by downregulating tight junction proteins in retinal endothelial cells. Clinically, the use of IL-6 inhibitors has been found to be efficacious primarily in the context of treatment-resistant non-infectious uveitis and secondary macular edema. IL-6 is a key cytokine in retinal inflammation and macular edema. It is thus not surprising that the use of IL-6 inhibitors in treatment-resistant macular edema in the setting of non-infectious uveitis has been well documented as an effective treatment option. The use of IL-6 inhibitors in macular edema secondary to non-uveitic processes has only begun to be explored.

Rheumatologist's Perspective on Non-Infectious Uveitis: Patterns from Tertiary Referral Rheumatologic Clinics in Italy.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.

Intravitreal fluocinolone acetonide 0.19 mg (ILUVIEN®) in patients with non-infectious uveitis: real-world effectiveness and safety outcomes at 12 months.

PURPOSE: This study assessed the effectiveness of the 0.19-mg fluocinolone acetonide (FAc) implant by multimodal measurements in patients with non-infectious uveitis (NIU) in a real-world setting in Spain. METHODS: A prospective study of patients who had NIU including uveitic macular oedema (UME) with ≥ 12 months follow-up was done. Exclusion criteria include infectious uveitis and uncontrolled glaucoma or ocular hypertension requiring more than 2 medications. Effectiveness was assessed using a multicomponent outcome measure that included nine outcomes. Effectiveness was defined as all components being met at every timepoint. Secondary outcome measures were onset or progression of glaucoma and investigator-reported adverse events. RESULTS: Twenty-six eyes from 22 patients were included, with 96.2% having an indication including UME. During the 12-month study, the FAc implant was effective in 15 (57.7%) eyes, reaching effectiveness as soon as 2 weeks post-implantation. Mean best-corrected visual acuity and mean central macular thickness (CMT) were significantly improved vs. baseline at all timepoints (all comparisons p < 0.01). During the 12-month study, inflammation markers (anterior chamber cells and vitreous haze) had also significantly declined. Factors predicting effectiveness at month 12 were systemic corticosteroid dose pre-FAc, higher immunomodulatory therapy (IMT) load at baseline and thicker retinal nerve fibre layer (RNFL) at baseline (all p < 0.05). Factors predicting failure were male gender, thinner RNFL at baseline and treatment ineffectiveness at 1 month (all p < 0.05). In parallel, corticosteroid and IMT use also declined significantly. No significant increase in IOP was detected. CONCLUSION: The FAc implant is safe and effective at treating NIU over 12 months in a real-world setting in Spain.

Intravitreal fluocinolone acetonide 0.19 mg (Iluvien®) for the treatment of uveitic macular edema: 2-year follow-up of 20 patients.

PURPOSE: To evaluate intravitreal 0.19 mg fluocinolone acetonide implant (FAi) (Iluvien®) for the treatment of chronic non-infectious uveitis with associated cystoid macular edema (CME). METHODS: A retrospective review of medical reports from a single Danish tertiary centre including 20 patients (20 eyes), treated with 0.19 mg FAi for non-infectious uveitic CME. The primary endpoints were change in best corrected visual acuity (BCVA) and central retinal thickness (CRT). The secondary endpoints were recurrence rate, change in systemic treatment, and intraocular pressure (IOP). RESULTS: Mean follow-up of the 20 eyes was 2.3 ± 1.1 years. BCVA improved at 6 (p = 0.13), 12 (p = 0.05), 18 (p = 0.03), and 24 months and CRT decreased at 6 (p = 0.004), 12 (p = 0.006), 18, and 24 months after 0.19 mg FAi. Within 18 months after implantation, four of 14 patients (28.6%) relapsed. Three of five patients discontinued systemic corticosteroids within 4 months and one patient continued with reduced dose. Five of 10 patients receiving disease-modifying antirheumatic drugs (DMARDs) at time of implantation discontinued within 1 year. No patients started new systemic treatment. Eight eyes were treated with topical IOP-lowering medication at the time of implantation, of these two later underwent trabeculectomy. There were no complications associated with previous glaucoma surgery. CONCLUSION: This long-term follow-up study showed that intravitreal treatment with 0.19 mg FAi should be considered in the treatment of chronic non-infectious uveitic CME in selected patients. This treatment is safe even in selected glaucoma patients and may offer reduction or cessation of local or systemic anti-inflammatory treatment.

Microbiome in Immune-Mediated Uveitis.

In the last decades, personalized medicine has been increasing its presence in different fields of medicine, including ophthalmology. A new factor that can help us direct medicine towards the challenge of personalized treatments is the microbiome. The gut microbiome plays an important role in controlling immune response, and dysbiosis has been associated with immune-mediated diseases such as non-infectious uveitis (NIU). In this review, we gather the published evidence, both in the pre-clinical and clinical studies, that support the possible role of intestinal dysbiosis in the pathogenesis of NIU, as well as the modulation of the gut microbiota as a new possible therapeutic target. We describe the different mechanisms that have been proposed to involve dysbiosis in the causality of NIU, as well as the potential pharmacological tools that could be used to modify the microbiome (dietary supplementation, antibiotics, fecal microbiota transplantation, immunomodulators, or biologic drugs) and, consequently, in the control of the NIU. Furthermore, there is increasing scientific evidence suggesting that the treatment with anti-TNF not only restores the composition of the gut microbiota but also that the study of the composition of the gut microbiome will help predict the response of each patient to anti-TNF treatment.

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.

Case of lens-induced uveitis associated with supernormal flicker ERG amplitudes after cataract surgery.

PURPOSE: To report our findings in a case of lens fragment-induced uveitis associated with supernormal flicker electroretinograms (ERGs) twenty months after the cataract surgery. METHODS: This is an observational case report. Full-field flicker ERGs were recorded with the RETeval system. Optical coherence tomography (OCT) and slit-lamp biomicroscopy were used to assess the uveitis during the follow-up period. RESULTS: A 70-year-old man, who had undergone cataract surgery 20 months earlier, visited our hospital with a complaint of decreased vision in his right eye. Slit-lamp biomicroscopy revealed corneal edema and a lens fragment was detected in the inferior part of the anterior chamber. OCT showed cystoid macular edema, and flicker ERGs showed a marked increase in the amplitude and a delay in the implicit time in the right eye. These abnormalities of the flicker ERGs improved gradually after the removal of lens fragment and application of topical anti-inflammatory medications. CONCLUSION: Our case of lens-induced uveitis had supernormal flicker ERG amplitudes. Clinicians should be aware that eyes with uveitis can have larger-than-normal ERG amplitudes.

A novel OCT signature in leukemic papillopathy masquerading as autoimmune or infectious uveitis.

PURPOSE: With therapeutic advances, central nervous system (CNS) involvement in leukemia has become more common. Leukemic optic disc infiltration, often a clinical diagnosis, can present as an isolated finding in primary or relapsed CNS disease and therefore requires early recognition. Not previously well appreciated, we report here signs of intraocular inflammation accompanying leukemic optic disc infiltration, suggesting infectious or non-infectious uveitis as an alternative diagnosis. We describe a novel optical coherence tomography (OCT) sign favoring leukemic infiltration. METHODS: Retrospective consecutive case series of all leukemic patients with disc edema (5 patients, 6 eyes) presenting to the University of Michigan's Ocular Oncology Clinic between October 2019 and March 2020. RESULTS: We report five leukemic patients (6 eyes) who were evaluated for disc edema and vitritis and eventually diagnosed with leukemic papillopathy. All five patients initially had a bland lumbar puncture (LP), and all four patients who underwent magnetic resonance imaging (MRI) had no retrobulbar nerve involvement. Clinical findings included preserved visual acuity (n = 5 eyes, 83%), anterior chamber (AC) cell (n = 3 eyes, 50%), vitreous cell (n = 6 eyes, 100%), and retinal whitening (n = 4 eyes, 66%). In five eyes (83%), a diagnosis of infectious or non-infectious uveitis was initially considered. The OCT finding of inner retinal thickening and loss of inner retinal lamination with largely preserved outer retinal architecture helped point towards a leukemic infiltrative process emanating from the disc and spreading retrograde through the nerve fiber layer. CONCLUSIONS: These cases highlight the difficulty of distinguishing intraocular inflammation associated with leukemic papillopathy from infectious or non-infectious uveitis, especially considering bland LP and negative retrobulbar MRI signal in all our patients. We propose juxtapapillary inner retinal infiltration with the loss of inner retinal lamination and relative preservation of outer retinal architecture on OCT imaging as a finding that supports the diagnosis of leukemic papillopathy.

Visual outcomes and choroidal thickness associated with human leukocyte antigen DRB1*04 in unclassifiable uveitis in Japanese patients.

PURPOSE: Human leukocyte antigen (HLA) and immunity are related. Uveitis is also closely related to immunity. For example, the common presence of human leukocyte antigen (HLA)-DRB1*04 in the immune response is well known. The aim of this study was to investigate the relationship between visual prognosis and various HLA alleles before and after therapy in patients with unclassifiable uveitis, excluding those with Vogt-Koyanagi-Harada (VKH) disease. METHODS: This retrospective case series included 42 eyes from 22 consecutive patients with unclassifiable uveitis, excluding those with VKH disease. Visual acuity (VA), sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and 6-month visits. Mean values of parameters were compared at each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primers. RESULTS: DRB1*04 showed a dominant change. No significant difference was observed in the other alleles. In DRB1*04, The mean differences in initial CCT, 6-month CCT, and 6-month VA showed statistically significant difference was found in best-corrected visual acuity (BCVA) between DRB1*04+ and DRB1*04- at the first visit. BCVA values at baseline and at the final visit were 0.13 ± 0.29 and 0.20 ± 0.36 in the DRB1*04+ and 0.00045 ± 0.20 and - 0.058 ± 0.11 in the DRB1*04- groups(p = 0.00465). Central Choroidal Thickness (CCT) values pretreatment and at the final visit after treatment were (pretreatment:361.00 ± 361.0 µm,after treatment: 286.00 ± 106.53 µm, p = 0.0174) in the DRB1*04+ group, and (pretreatment:281.3 ± 139.68 µm,after treatment:223.85 ± 99.034 µm, p = 0.0426) in the DRB1*04- group, respectively, indicating changes between baseline and the final visit. CCT was significantly greater in the DRB1*04+ group at both the initial visit and at 6 months. Multivariate analysis showed a significant difference between the presence or absence of DRB1*04 and sex. CONCLUSION: HLA-DRB1*04 allele may affect visual prognosis and CCT in unclassifiable uveitis.

Complete blood count parameters and neutrophil-to-lymphocyte ratio values as markers for differentiation between systemic infectious and non-infectious uveitis.

PURPOSE: To compare complete blood count (CBC) parameters and neutrophil/lymphocyte ratio (NLR) between patients with infectious uveitis (IU) and those with non-infectious uveitis (NIU) during the first acute uveitis attack (AUA). METHODS: The records of 119 patients admitted with the first AUA between 2016 and 2019 and whose diagnosis was unknown at the time of admission were retrospectively reviewed. The patients were divided into two groups, IU and NIU according to diagnoses after ocular and systemic workup. The IU group was also divided into subgroups as uveitis associated with local ocular infections and systemic infections. The complete blood count and associated indices of patients calculated from samples taken during the attack were compared between the groups. RESULTS: A total of 60 NIU cases (mean age: 43.5 ± 11.6 years) and 59 IU cases (43.3 ± 14.7 years) were examined. Twenty-six of the NIU cases were female and 34 were male, while 32 of the IU cases were female and 27 were male. The localization of uveitis was similar in the IU and NIU groups (anterior: 11 vs. 18, intermediate: 3 vs. 6, posterior: 28 vs. 14, panuveitis: 17 vs. 22). The NLR values were significantly increased in patients with IU compared to those with NIU (p = 0.047). When the NLR is compared between NIU and subgroups of IU, this value was only found significantly increased in uveitis due to a systemic infection (n = 12) (p < 0.001). The mean white blood cell (WBC) count (p < 0.001) and neutrophil values (p < 0.001) were also observed significantly higher in the uveitis associated with systemic infectious diseases when compared with uveitis associated with local ocular infections and NIU group. CONCLUSION: In the current study, NLR values are compared with autoimmune uveitis and systemic infectious uveitis for the first time in patients with AUA. This ratio has been found significantly higher in uveitis associated with systemic infections. The use of CBC parameters and indices, especially the NLR, may be instrumental in assessing patients presenting with first AUA, particularly when there is no clear explanation or underlying cause.

Recent advances in the management of non-infectious posterior uveitis.

PURPOSE: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). METHODS: We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. RESULTS: The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. CONCLUSION: Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.

[Viral and non-viral infections in the etiopathogenesis of uveitis]. / Virusnye i drugie infektsii v étiopatogeneze uveitov.

The article reviews literature and proprietary data on the role of pathogens in the etiology of infectious and non-infectious uveitis. Infectious uveitis is caused by active intraocular replication of the virus (herpesvirus, acute stage of enterovirus), or by long-term persistence of the viruses in eye tissues (Fuchs syndrome associated with rubella virus, late complications of enterovirus uveitis). Clinical picture, severity, outcomes of infectious uveitis depend on the pathogen, adequacy of the immune response and genetic characteristics of the patient. Infections trigger the development of non-infectious uveitis, including autoimmune. Their trigger mechanisms involve antigenic mimicry, bystander activation, epitope spreading, presence of superantigens, intestinal microbiota. An uncontrolled, excessive host immune response contributes to cell destruction even after removal of the infection.

Intravitreal dexamethasone implants for non-infectious uveitis.

IMPORTANCE: Inflammatory-mediated cystoid macular oedema (CMO) is the most common inflammatory-mediated threat to vision in non-infectious uveitis (NIU). Corticosteroid therapy is the cornerstone to the management of CMO in NIU. Sustained-release dexamethasone (DEX) implant devices provide localized therapy. BACKGROUND: The authors present a series documenting the efficacy of DEX implants for NIU in an Australian cohort. DESIGN: A single centre, retrospective case series patients receiving DEX implants for NIU from 2012 to 2018 in a New South Wales tertiary eye hospital. PARTICIPANTS: Twenty eyes of 17 patients receiving DEX implants for confirmed cases of NIU of varying aetiologies. METHODS: Cases from March 2012 and March 2018 were retrospectively selected with follow-up assessment data recorded and analysed. All patients were seen at 1, 2 and 4 weeks post implant, then monthly. Minimum duration of follow-up was 32 weeks. MAIN OUTCOME MEASURES: The primary outcome was change in central retinal thickness (CRT) of >20% at two consecutive visits. Secondary outcomes included change in best-corrected visual acuity (BCVA), intraocular pressure and medication regimens. RESULTS: Ninety-five percent of patients achieved significant CRT reduction at 4, 8 and 16 weeks (P < .01). Sixty-one percent demonstrated improved BCVA at week 8 (P < .05). Ninety percent of patients taking systemic corticosteroid therapy at commencement reduced their dose to below 7.5 mg/day. Adverse event frequency was low. CONCLUSIONS AND RELEVANCE: In keeping with larger studies, the authors suggest that DEX implants may effectively control uveitis refractory to other therapy, while improving BCVA and CRT. In addition, DEX usage has demonstrably reduced systemic steroid burden within the observed cohort.

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

Superficial and deep retinal foveal avascular zone OCTA findings of non-infectious anterior and posterior uveitis.

PURPOSE: To compare the superficial (FAZ-S) and deep foveal avascular zones (FAZ-D) of non-infectious anterior and posterior uveitis to healthy controls, using optical coherence tomography angiography (OCTA). METHODS: OCTA was performed on 74 eyes: 34 eyes with non-infectious posterior uveitis (with (post+CME) and without macular edema (post-CME)), 11 eyes with non-infectious anterior uveitis (with (ant+CME) and without macular edema (ant-CME)), and the control group which included 29 healthy eyes. RESULTS: Eyes suffering from non-infectious posterior uveitis presented with significantly larger FAZ-D when compared to healthy controls, both in the presence or in the absence of macular edema (p < 0.001). In the presence of macular edema, eyes presenting with anterior uveitis (ant+CME) also showed significantly larger FAZ-S (p = 0.03) and FAZ-D (p < 0.001), when compared to healthy controls. In the absence of macular edema, eyes with anterior uveitis cannot be distinguished from controls (p > 0.6). CONCLUSION: The deep retinal foveal avascular zone seems to be enlarged in eyes presenting with non-infectious posterior uveitis, both in the presence or absence of macular edema.

Carbon monoxide-releasing molecule-A1 (CORM-A1) improves clinical signs of experimental autoimmune uveoretinitis (EAU) in rats.

Uveitis is a sight-threatening inflammatory disease of the eye which represents the third leading cause of blindness in the developed countries. The conventional pharmacological treatment includes corticosteroids and immunosuppressive agents, which are limited by their side effects. New therapeutic strategies are thus strongly needed. Exogenously-administered carbon monoxide (CO) may represent an effective treatment for conditions characterized by a dysregulated inflammatory response. Carbon monoxide-releasing molecules (CORMs) are a novel group of compounds capable of carrying and liberating controlled quantities of CO. Among CORMs, CORM-A1 represents the first example of water soluble CO releaser. We show here that CORM-A1 under a late prophylactic regime is able to significantly ameliorate the natural course of experimental autoimmune uveoretinitis, a rodent model of immunoinflammatory posterior uveitis. The present study strongly supports the development of CORM-A1 as a potential new drug for treatment of patients with non-infectious posterior uveitis.

Treatment Impact on the Long-Term Ocular Outcomes in Behçet's-Related Uveitis.

PURPOSE: To examine the demographic characteristics, findings and complication rates in patients with Behçet's uveitis (BU) and to investigate the effect of early biological therapy on the development of complications. METHODS: Medical records of 94 patients with BU were retrospectively reviewed. Demographic data, ocular findings and complications at presentation, complications during follow-up, and treatments received during follow-up were analyzed. Patients who were followed for at least 24 months were divided into two groups according to the time of presentation as Group 1 (between 2009 and 2015) and Group 2 (between 2016 and 2021). Complications at the time of presentation and during follow-up, and treatments were compared. RESULTS: We enrolled 94 patients with a male-to-female ratio of 1.94 with a mean age of 30 ± 12 years. Median follow-up was 58.1(12-163) months. There were 35 patients (66 eyes) in Group 1 and 33 patients (61 eyes) in Group 2. At the time of presentation, end-stage disease, cataract, epiretinal membrane, and optic atrophy were significantly more common in Group 1 than in Group 2 (p < 0.05). A significantly higher proportion of eyes in Group 1 developed macular edema, cataract, epiretinal membrane, and macular atrophy during-follow-up (p < 0.05). Median time to initiation of biological treatment was 17.29 months in Group 1 and 3.33 months in Group 2 (p < 0.001). The overall complication rate was significantly lower in Group 2. CONCLUSIONS: Prognosis of BU is improved after the introduction of biological treatment. Early use of biological agents in BU is effective in decreasing sight-threatening ocular complications.

Rituximab in the Treatment of Non-Infectious Uveitis: A Review.

Non-infectious uveitis (NIU) is an immune-mediated disorder manifesting as ocular pain, redness, floaters, and photophobia, and is a leading cause of preventable blindness. Managing NIU presents considerable challenges due to the condition's resistance to high-dose corticosteroids and various immunotherapies. This review assesses the efficacy and safety of rituximab (RTX) in the treatment of NIU, based on individual case reports and small-scale studies. A cohort of 78 patients (20 males, 58 females), with a mean onset age of 32.3 years (range 8-72), was analyzed. Juvenile idiopathic arthritis (JIA) was the most frequently associated comorbidity, affecting 28 patients, while anterior uveitis was the predominant subtype, observed in 26 of 47 cases. Prior to RTX therapy, patients had been treated with an average of 1.7 conventional immunosuppressive agents (range 0-5) and 1.1 biologics (range 0-4). RTX was introduced following the failure of high-dose corticosteroids, immunosuppressive drugs, and biologics to control the uveitis. The median time from diagnosis to RTX initiation was 7.7 years (range 0.25-21). Post-RTX, 44.2% of patients experienced improvement in visual acuity, 79.5% achieved resolution of ocular inflammation, and 8.9% showed partial improvement. Additionally, 81.1% were able to reduce their corticosteroid dosage. Overall, 88.6% (69 out of 78) demonstrated a positive response to RTX treatment. These findings indicate that RTX may serve as an effective therapeutic option for NIU unresponsive to steroids and multiple immunotherapies. It may also warrant consideration as a potential first-line treatment in certain cases.

Unraveling the Spectrum of Uveitis: Insights from an Epidemiological Study in a National Referral Center in Northern Italy.

PURPOSE: Uveitis embraces a heterogeneous group of vision-threatening inflammatory conditions. Understanding uveitis epidemiology, etiology, and clinical findings is fundamental for a prompt diagnosis and optimal patient management. The aim of the study is to report the epidemiology of uveitis in a national referral center in Northern Italy and investigate the visual prognosis. METHODS: This retrospective study was conducted at Uveitis Service (Ospedale San Raffaele) between June 2016 and May 2023. Demographic data, clinical characteristics, and etiological diagnoses of uveitis patients were collected, and visual prognosis was longitudinally explored. RESULTS: 1105 patients with uveitis were included in the study, while 47 patients presented neoplastic masquerade syndrome and have been excluded. The population had a slight majority of females (M/F ratio = 0.76), mean age was 47 years. 25% presented infectious uveitis, primarily due to herpetic etiology, toxoplasmosis, and tuberculosis. Non-infectious uveitis was the most prevalent diagnosis (38%), with sarcoidosis, HLA-B27-associated uveitis, and Fuch's uveitis as prominent causes. Anatomically, anterior segment was most frequently involved (41%). Significant improvement in visual acuity was observed at follow-up, particularly in patients with infectious uveitis. CONCLUSIONS: Our study sheds light into the epidemiological landscape of uveitis in Northern Italy, reflecting changing patterns due to factors such as migration and changing sexual habits. In particular, higher percentages of syphilis have been observed, compared to other European reports. The distribution of non-infectious uveitis reflects other epidemiological European series. Higher percentages of neoplastic masquerade syndromes support the need of early recognition. Our findings offer precious insights for uveitis epidemiology and daily clinical practice.