RARE DISEASE
Anterior uveitis
Anterior uveitis
Anterior uveitis
Synonyms: Iridocyclitis
Synonyms: Iridocyclitis
Synonyms: Iridocyclitis
Drug discovery
2
drugs
With orphan designations
Overview
Anterior uveitis (AU) is the most common form of uveitis, characterized by inflammation of the iris and ciliary body. Symptoms include ocular pain, photophobia, blurred vision, and conjunctival redness, often presenting acutely but may become chronic or recurrent. Up to 52% of cases have systemic associations, including HLA-B27-related spondyloarthropathies or infections like herpesviruses. Diagnosis requires slit-lamp evaluation for anterior chamber cells/flare and targeted testing for etiology [1][6][11].
Burden
Responsible for 10% of legal blindness in the US, with complications including glaucoma (20%), cataracts, and cystoid macular edema [1][16].
Annual US healthcare costs exceed $241 million, driven by frequent monitoring (5-7 visits per acute episode) and biologics [8][13].
Chronic cases incur 2.5x higher productivity losses vs controls due to visual impairment [16][17].
Therapies
First-line: Aggressive topical corticosteroids (e.g., prednisolone acetate 1% hourly) and cycloplegics (e.g., cyclopentolate) [1][3][11].
Refractory cases: Periocular/intravitreal steroids (triamcinolone) or systemic immunomodulators (methotrexate, adalimumab) [8][13][18].
Infectious causes: Antivirals (acyclovir/valacyclovir for herpesviruses) with concurrent steroids [5][11].
Categories: rare ophthalmic disorders
Research Papers
1,278 drug discovery papers about Anterior uveitis, with 3 first-in-class and 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,278 drug discovery papers about Anterior uveitis, with 3 first-in-class and 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-28 | Fibrinous Acute Anterior Uveitis as a Manifestation of Poorly Controlled Type 2 Diabetes Mellitus
A male patient with diabetes presented with acute painful red eye associated with diminution of vision in the left eye. Ocular examination revealed severe fibrinous anterior uveitis: a dense anterior chamber reaction, with posterior synechiae. Infectious and autoimmune etiologies were excluded with thorough investigations, and uncontrolled hyperglycemia was attributed as likely precipitating factor. The patient responded rapidly to intensive topical corticosteroids and optimization of systemic diabetic therapy. This case highlights the association of poorly controlled diabetes mellitus with severe intraocular inflammation and emphasizes the importance of clinicians considering diabetes mellitus-associated anterior uveitis in patients with significant metabolic dysregulation.
2026-09-11 | Topical versus oral antiviral therapy for cytomegalovirus anterior uveitis: a multicenter study in Taiwan.
To compare topical and oral antiviral therapies for cytomegalovirus (CMV) anterior uveitis (AU) in terms of efficacy. This retrospective study included 240 patients with CMV AU who received treatment at Chang Gung Memorial Hospital between 2007 and 2019. Their diagnoses were confirmed through aqueous polymerase chain reaction. The mean follow-up duration was 4.0 ± 3.1 years. The proportion of patients with an acute uveitis course, defined as no anti-CMV medication use beyond 3 months after diagnosis, was higher in patients initially treated with oral valganciclovir than in those initially treated with topical ganciclovir (40.0% vs. 15.7%; p = 0.038). Patients initially treated with topical ganciclovir plus oral valganciclovir were least likely to develop chronic disease (combined therapy vs. topical therapy vs. oral therapy: 5.0% vs. 39.3% vs. 20.0%; p = 0.007). Within 3 years, the risk of glaucoma surgery or laser intervention was lower in the acute group compared with the chronic (odds ratio [OR]: 0.25, 95% confidence interval [CI]: 0.08-0.82) and recurrent (OR: 0.32, 95% CI: 0.11-0.92) groups. The risk of corneal transplantation was lower in both the acute and chronic groups compared with the recurrent group (OR: 0.17, 95% CI: 0.05-0.56; and OR: 0.28, 95% CI: 0.09-0.86, respectively). Compared with topical ganciclovir, oral valganciclovir is associated with a lower risk of recurrent and chronic CMV AU. Chronic and recurrent disease are associated with increased risk of glaucoma requiring intervention, and recurrent disease carries an additional risk of corneal decompensation.
2026-08-24 | Bilateral anterior and intermediate uveitis associated with parvovirus B19 infection in a pediatric patient: A case report
To describe a rare case of bilateral anterior and intermediate uveitis associated with parvovirus B19 infection in a pediatric patient and highlight diagnostic and therapeutic considerations. A 5-year-old boy presented with bilateral ocular pain, conjunctival hyperemia, and decreased visual acuity one week after hospitalization for systemic parvovirus B19 infection. Laboratory investigations excluded other infectious and autoimmune causes. Ophthalmologic examination revealed bilateral anterior chamber inflammation and vitritis. B-scan ultrasonography confirmed vitreous opacities. Polymerase chain reaction (PCR) analysis of anterior chamber fluid was performed to determine the etiologic agent. PCR testing detected parvovirus B19 DNA in the anterior chamber fluid, confirming the diagnosis. Initial treatment with intensive topical corticosteroids and cycloplegic agents failed to control inflammation. Subconjunctival dexamethasone injection resulted in rapid resolution of ocular inflammation and complete recovery of visual acuity. Parvovirus B19 should be considered in pediatric patients presenting with bilateral uveitis following systemic viral symptoms.
2026-07-30 | AYURVEDIC MANAGEMENT OF ACUTE ANTERIOR UVEITIS (PITTAJA ADHIMANTHA): A CASE REPORT
Introduction: Uveitis is an inflammatory disorder of the vascular layer of the eyeball and accounts for approximately 10% of blindness. Anterior uveitis denotes inflammation of the iris and/or the anterior part of the ciliary body and is characterized by pain, photophobia, ciliary congestion, blurred vision and keratic precipitates; if not treated promptly it can cause complications such as glaucoma, cataract, cystoid macular oedema and retinal detachment. Case presentation: A 40‑year‑old male presented with bilateral ocular pain, redness, watering, photophobia and blurred vision for 4–5 days, diagnosed as anterior uveitis and correlated with Pittaja Adhimantha according to Ayurveda. He was treated with Jalaukavacharana (leech therapy) on day 1 and day 7 along with internal medications: Gokshuradi Guggulu 250 mg – 2 tablets twice daily for 7 days, a ghrita preparation 3 g twice daily for 7 days, Saptamrita Lauha 1 tablet twice daily for 15 days and Triphala Avaleha 1 teaspoon once daily for 15 days. Results: By the third day of treatment, ocular pain, redness, photophobia, watering and blurring of vision had reduced by about 50% compared with baseline, and by the seventh day the patient became completely asymptomatic. Conclusion: The combination of Jalaukavacharana with internal Pitta‑shamana medicines including Gokshuradi Guggulu, ghrita, Saptamrita Lauha and Triphala Avaleha proved effective in this case of acute anterior uveitis (Pittaja Adhimantha), suggesting a useful Ayurvedic alternative or adjunct to steroid‑based management.
2026-07-19 | AYURVEDIC MANAGEMENT OF RECURRENT ANTERIOR UVEITIS (RAKTAJA AD-HIMANTHA): A CASE STUDY
A 40-year-old male patient came to the Ophthalmology OPD in December 2025 with complaints of redness, water-ing (epiphora), blurred vision and pain in the left eye for the last 5-7 days. On detailed history-taking, the patient reported that similar episodes had recurred every 15-20 days over the past year, significantly affecting daily functioning. Based on clinical signs, symptoms, and Ayurvedic diagnostic pa-rameters, the condition was diagnosed as Raktaja Adhimantha. The patient was managed with an Ayurvedic thera-peutic protocol comprising Jalaukavacharana (leech therapy), Netraseka, and oral Ayurvedic medicines. The symp-toms resolved within 21 days, and the anterior chamber findings returned to normal after almost one month. Oral medication was continued for two months. Patient remains symptom-free for four months. Thereafter, no recur-rence was noticed till May 2026. Raktamokshana, along with netraseka and oral medication, is effective in recur-rent anterior uveitis.
proteins
2026-08-27 | IVIG-associated anterior uveitis resolving after switch to subcutaneous immunoglobulin.
Intravenous immunoglobulin (IVIG) therapy can occasionally induce unexpected inflammatory complications. A case report and literature review. We report a patient with hypogammaglobulinemia and systemic autoimmunity who developed reproducible unilateral anterior uveitis following IVIG administration across multiple formulations. Discontinuation of IVIG resolved the ocular inflammation but caused underlying disease exacerbation. Transition to facilitated subcutaneous immunoglobulin (SCIG) achieved stable serum IgG levels and maintained complete ocular and systemic remission over a four-year follow-up period. This case demonstrates peak-driven immune activation as a plausible mechanism for IVIG-induced uveitis and highlights SCIG as a safe, effective therapeutic alternative that bypasses rapid peak IgG dynamics while preserving immune protection.
2026-08-24 | Local therapy in uveitis: Current concepts and emerging strategies.
Local therapy plays a pivotal role in the management of noninfectious uveitis, providing targeted drug delivery with reduced systemic adverse effects. Advances in corticosteroid formulations and delivery routes have significantly improved therapeutic outcomes. Topical corticosteroids remain first-line for anterior uveitis, while periocular and intravitreal injections such as triamcinolone acetonide and dexamethasone implants (Ozurdex®) are effective for intermediate and posterior disease. Long-acting fluocinolone acetonide implants (Retisert®, Yutiq®) offer sustained control for chronic or recurrent cases, though ocular hypertension and cataract formation are common. The introduction of suprachoroidal corticosteroid delivery (Xipere®) allows precise posterior segment targeting with fewer anterior complications. Nonsteroidal intravitreal agents, including methotrexate and sirolimus, serve as steroid-sparing options, and topical immunomodulators such as cyclosporine and tacrolimus can be rarely used in chronic anterior uveitis. Emerging modalities like intravitreal biologics, nanocarrier systems, and gene-based delivery hold promise for long-term disease modulation. A tailored, evidence-based approach to local therapy can optimize inflammation control and visual outcomes in uveitis management.
2026-06-16 | Supramolecular peptide hydrogels for the treatment of ocular diseases: from tissue replacements to drug delivery systems.
Supramolecular peptide hydrogels (SPHs), a unique class of dynamic three-dimensional networks formed by self-assembly of peptides, have demonstrated strong potential for ocular tissue replacement and drug delivery in ophthalmic applications. On the one hand, their mechanical and physiochemical properties can be precisely tailored via rational design of peptides to emulate native ocular tissues. On the other hand, the intrinsic dynamic features of SPHs enable efficient encapsulation of commercial drugs and incorporation of stimuli-responsive or targeting moieties, which in turn facilitate ocular barrier penetration and enhance therapeutic efficacy. In this review, we systematically summarize recent advances of the use of SPHs in ocular disease treatment, focusing on their design principles and two key application aspects: ocular tissue substitutes (for vitreous and corneal repair) and drug delivery systems targeting prevalent ocular pathologies, including dry eye disease, corneal neovascularization, bacterial keratitis, anterior uveitis, diabetic retinopathy, and age-related macular degeneration. These findings highlight the promising potential of SPHs as next-generation biomaterials for precision ophthalmic therapy.
2026-04-22 | Concurrent herpetic hypertensive anterior uveitis and cytomegalovirus retinitis in a non-HIV patient with melanoma differentiation-associated gene-5 dermatomyositis: intravenous immunoglobulin comes to the rescue.
Melanoma differentiation-associated gene 5 dermatomyositis (MDA-5 DM) is a rare subtype of dermatomyositis. Cytomegalovirus (CMV) retinitis is an opportunistic ocular infection that has historically been linked to HIV infection. Herpes simplex virus (HSV) uveitis is caused by the reactivation of the varicella-zoster virus. We present the case of a 69-year-old woman diagnosed with aggressive MDA-5 DM associated with interstitial lung disease, who received multiple immunosuppressive therapies and subsequently developed left eye CMV retinitis and right eye acute herpetic, hypertensive, anterior uveitis with dendritic keratitis. After the diagnosis of MDA-5 DM, she was treated with glucocorticoids (GC), followed by rituximab and triple therapy (cyclosporine, cyclophosphamide, and GC); however, she did not improve and multiple adverse effects occurred. The patient then started tofacitinib (TOF) and improved. While being on TOF, she developed right eye acute herpetic, hypertensive, anterior uveitis, followed by left eye CMV retinitis. TOF was stopped, and the patient started oral acyclovir and intravenous and intravitreal ganciclovir, which was later changed to maintenance therapy with oral valganciclovir. Cyclical intravenous immunoglobulin (IVIG) administration was started, resulting in an overall improvement in disease activity associated with MDA-5 DM. This case underscores the uncommon link between CMV retinitis in a non-HIV patient and HSV anterior uveitis in a patient undergoing immunosuppressive therapy and the challenge of treating MDA-5 DM with IVIG, which led to favorable results.
2026-01-21 | Successful goniosynechialysis for secondary angle-closure glaucoma after ocular jellyfish sting.
Little is known about the ocular effects of jellyfish stings and their optimal management. We report the case of a 25-year-old fisherman that presented to the Emergency Department with a painful red eye, photophobia and blurred vision 24 hours after a jellyfish sting in his right eye (RE), that was projected from a fishing net. Visual acuity of the RE was 20/80. Examination of the RE revealed anterior uveitis, areas of iris stromal atrophy, 360° peripheral anterior synechiae (PAS) and intraocular pressure (IOP) of 45 mmHg. Left eye was normal. Anterior segment inflammation resolved with topical anti-inflammatory therapy, but IOP remained uncontrolled despite maximal hypotensive therapy. Two months later, goniosynechialysis was performed and restored aqueous outflow, achieving long-term IOP control. The surgery was uneventful, and PAS were separated from the angle using micro-forceps. This case highlights important ocular findings - acute iris stromal atrophy, extensive PAS and severe ocular hypertension - secondary to jellyfish toxins, raising awareness to the rare entity of jellyfish stings. Early recognition and prompt surgical intervention may be sight-saving, in cases of ocular jellyfish stings, preventing the development of secondary chronic angle-closure glaucoma.
antibodies
2026-09-22 | Advances in tumor necrosis factor-α inhibitors for the treatment of juvenile idiopathic arthritis-associated uveitis.
Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a common and sight-threatening extra-articular manifestation of juvenile idiopathic arthritis, typically presenting as chronic noninfectious anterior uveitis. Its early symptoms are often insidious, and delayed detection and treatment may lead to cataract, glaucoma, macular edema, and irreversible visual impairment. Conventional treatment is based on glucocorticoids and immunosuppressants; however, some children continue to experience inadequate efficacy, glucocorticoid dependence, drug intolerance, or adverse events. In recent years, substantial progress has been made in the use of biologics for JIA-U. Among them, tumor necrosis factor-α inhibitors, particularly adalimumab, have shown potential for controlling ocular inflammation, reducing glucocorticoid exposure, and improving visual outcomes, thereby offering a new therapeutic avenue for patients with JIA-U. Although TNF-α inhibitors have become an important component of systemic therapy for JIA-U, optimal dosing, long-term maintenance, tapering, and the timing of discontinuation require further investigation. Additional prospective, disease-specific pediatric studies are needed to define the optimal timing of TNF-α inhibitor initiation, precise dose-adjustment strategies, and long-term safety management, thereby advancing individualized and precision treatment for JIA-U.
2026-09-18 | Biologic Therapy in Refractory Non-Infectious Uveitis: An Analysis of 60 Cases at a Tertiary Eye Care Centre from South India.
To evaluate the effectiveness and safety of biologic therapy in patients with refractory non-infectious uveitis (NIU) in a real-world clinical setting. A retrospective observational study was conducted at a tertiary eye care centre in South India between 2022 and 2025. Patients diagnosed with NIU, who were not responding to conventional treatment and had received biologics during this period, were included. Demographic details, anatomical classification, etiological diagnosis, type of biologic used, treatment duration, clinical outcomes, and adverse events were analysed. A total of 60 patients with refractory NIU receiving biologic therapy were included. The mean age at biologic initiation was 23.1 ± 13.7 years, comprising 27 (45%) paediatric and 33 (55%) adults. The mean duration of uveitis prior to biologic initiation was 34.48 ± 52.36 months. Anterior uveitis was the most common (40%). Autoimmune etiologies predominated, with juvenile idiopathic arthritis-associated uveitis (28.3%), HLA-B27-associated uveitis (23.3%), and Behçet disease (20%). Adalimumab was the most frequently used biologic agent (88.3%) followed by Infliximab (5%), golimumab (3.3%) and tocilizumab (3.3%). Biologic therapy resulted in significant control of intraocular inflammation (p < 0.0001). Visual acuity remained stable throughout the follow-up. Treatment modification was required in 7 patients (11.7%). Side effects were observed in 3 (5%) patients, 2 (3.3%) showed inadequate response and 2 patients (3.3%) discontinued biologics due to financial constraints. Biologic therapy is an effective and safe therapy for refractory non-infectious uveitis across all age-groups and etiologies. Early escalation to biologics may help arrest long-term cumulative inflammatory damage and preserve visual function by sustained inflammatory control.
2026-09-10 | Biologic and targeted synthetic therapies in ankylosing spondylitis: a pharmacological review.
Ankylosing spondylitis (AS) is a prototypical axial spondyloarthritis (axSpA) defined by chronic inflammatory back pain, progressive spinal stiffness, and frequent extra-articular manifestations such as acute anterior uveitis (21%-33%), inflammatory bowel disease (5%-10%), and psoriasis (4%-13%). Management has shifted from non-steroidal anti-inflammatory drugs (NSAIDs) to highly targeted biologic and synthetic disease-modifying antirheumatic drugs (DMARDs). This comprehensive review focuses on the current evidence for biologic and targeted synthetic therapeutics in the management of AS, emphasizing mechanisms of action, regulatory approvals, dosing regimens, and clinical efficacy. Three major therapeutic classes are identified: two biologic DMARD classes, comprising tumor necrosis factor-alpha (TNF-α) inhibitors and interleukin-17 (IL-17) inhibitors, and the targeted synthetic DMARDs, namely, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, certolizumab pegol) typically achieve Assessment of Spondyloarthritis International Society 40% improvement (ASAS40) rates of 40%-58% at 12-24 weeks versus 13%-24% with placebo, and maintain clinical benefit in many patients over 5-8 years. IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, brodalumab, netakimab) yield broadly similar ASAS40 responses (30%-50% versus 10%-20% placebo) and are particularly useful in patients with concomitant psoriasis with substantially reduced risk of tuberculosis reactivation. JAK inhibitors (tofacitinib, upadacitinib) represent the newest class, offering oral administration with ASAS40 responses of 40%-52% versus 13%-26% for placebo in both biologic-naïve and biologic-experienced AS, though cardiovascular safety considerations necessitate careful patient selection. Therapeutic selection should consider comorbidities (uveitis favors TNF monoclonal antibodies; psoriasis favors IL-17 inhibitors), safety profile, route of administration, and sequencing after non-steroidal anti-inflammatory drug failure. Understanding these pharmacological distinctions enables personalized therapeutic decisions based on the specific molecular pathology and risk profile of the individual patient.
2026-08-29 | Comparison of the Risk of Acute Anterior Uveitis Flare Between Adalimumab and Subcutaneous Infliximab in Patients with Radiographic Axial Spondyloarthritis and Prior Acute Anterior Uveitis: A Randomized Controlled Trial.
Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation of radiographic axial spondyloarthritis (r-axSpA) and is an important consideration when selecting biological therapy. Although adalimumab (ADA) and infliximab are commonly used in patients with r-axSpA and AAU, direct comparative evidence, particularly between ADA and subcutaneous infliximab (IFX-SC), remains limited. The objective of this study was to compare the risk of AAU flare between ADA and IFX-SC in patients with r-axSpA and a history of AAU. This multicenter, head-to-head, randomized, open-label trial enrolled patients with r-axSpA and a documented AAU event within the preceding 2 years. Participants were randomly assigned (1:1) to receive ADA (40 mg every 2 weeks) or IFX-SC (intravenous 5 mg/kg induction followed by subcutaneous 120 mg every 2 weeks) and were followed for 48 weeks. The primary endpoint was AAU flare occurrence. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Secondary endpoints included changes in best-corrected visual acuity (BCVA), r-axSpA disease activity and functional indices, and safety outcomes. Fifty-six patients were randomized (ADA, n = 28; IFX-SC, n = 28). During follow-up, one AAU flare episode occurred in each group. The adjusted HR of IFX-SC (vs ADA) for an AAU flare was 0.496 (95% confidence interval 0.025-9.768, p = 0.645). No significant differences in secondary endpoints were observed between groups (right BCVA, p = 0.622; left BCVA, p = 0.306; Axial Spondyloarthritis Disease Activity Score, p = 0.293; Bath Ankylosing Spondylitis Disease Activity Index, p = 0.262; Bath Ankylosing Spondylitis Functional Index, p = 0.307). Adverse events were similar in frequency and severity, with no new safety signals identified. No statistically significant differences in AAU flare risk or secondary ocular and rheumatologic outcomes were observed between ADA and IFX-SC over 48 weeks in patients with r-axSpA and prior AAU. These findings suggest that IFX-SC may represent a potential alternative to ADA for AAU flare prevention as well as disease activity control in this population. Clinical Research Information Service (CRIS), Republic of Korea; KCT0007239.
2026-07-18 | Treatment of spontaneous hyphema in Fuch's heterochromic iridocyclitis with intravitreal anti-VEGF ranibizumab.
Fuch's heterochromic iridocyclitis (FHI) is a unilateral ocular condition characterised by low-grade anterior uveitis. Although the underlying aetiology remains unclear, proposed triggers include infections, autoimmune mechanisms and genetic predisposition. Amsler's sign is a recognised complication of FHI whereby patients develop spontaneous hyphaema that is often self-limiting. Current management of FHI focuses on managing complications such as raised intraocular pressures (IOPs), secondary glaucoma and formation of cataracts rather than the inflammation itself. In this case report, we present a patient with FHI complicated by spontaneous hyphaema and acute-on-chronic ocular hypertension refractory to medical therapy. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) ranibizumab was used, which achieved rapid resolution of hyphaema with resultant reduction in IOP. Subsequent trabeculectomy was performed for definitive control of persistent chronic ocular hypertension. This case highlights anti-VEGF therapy as a potential adjunctive strategy in selected patients presenting with similar clinical challenges.
cell therapies
2025-04-03 | Human umbilical cord-derived mesenchymal stem/stromal cells via suprachoroidal injection: A novel approach for experimental uveitis treatment
Uveitis is a group of vision-threatening inflammatory diseases, and current treatment options are mainly limited to corticosteroids, which often have side effects and do not address the underlying immune dysregulation. Mesenchymal stem/stromal cells cultivated in vitro have gained attention for their immune-regulating, neurotrophic, and tissue-regenerative properties, making them a promising candidate for treating uveitis. This study investigates the safety and efficacy of human umbilical cord derived mesenchymal stem/stromal cells (HUMSCs) combined with a novel suprachoroidal microinjector for targeted delivery in a rabbit model of experimental uveitis (EU). No significant clinical or histological changes were observed following HUMSCs injection in normal Chinichilla rabbit eyes. In the EU model, treatment with HUMSCs and triamcinolone acetonide (TA) significantly alleviated uveitis symptoms compared to phosphate-buffered saline, with notable improvements in anterior chamber inflammation and vitreous opacity scores. Both treatments also reduced the levels of inflammatory cytokines (TNF-α, VEGF, MIP-1α, IL-17A, bFGF) in the aqueous humor. Histological and immunofluorescence analyses showed decreased inflammatory cell infiltration and microglial activation. Additionally, RNA sequencing revealed that HUMSCs injection downregulated key genes in the Th17 differentiation pathway, which plays a critical role in the pathogenesis of EU. These findings establish the safety and efficacy of suprachoroidal injection of HUMSCs, highlighting their potential as an effective, targeted therapeutic approach for uveitis, with results comparable to TA.
2018-03-13 | Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?
Purpose of review The intestinal microbiome is thought to play a role in the pathogenesis of inflammatory bowel disease (IBD). There are many shared clinical manifestations between IBD and spondyloarthritis (SpA), of which the most common are peripheral arthritis and uveitis. Clinical overlap along with similar genetics between these diseases suggests a possible shared pathogenetic mechanism, which might center on the intestinal microbiota. In this review, we discuss the available evidence that SpA is a microbiome-driven disease and indicate how SpA-associated uveitis could be tied to gut dysbiosis. We conclude by discussing different treatment paradigms targeting the intestinal microbiome for SpA. Recent findings Recent studies support the growing evidence of the intestinal microbiome as a crucial player in SpA disease pathogenesis. There is emerging evidence that the gut microbiome may play a causative role in uveitis. Summary The field is beginning to discover a new level of understanding how the intestinal microbiome is involved in SpA. Treatment methods to alter intestinal microbiota to treat SpA-related diseases are still in its infancy.
2008-11-17 | Tolerance to melanin-associated antigen in autoimmune uveitis is mediated by CD4+CD25+ T-regulatory cells.
Experimental autoimmune anterior uveitis (EAAU) serves as an animal model for human idiopathic AU, the most common form of intraocular inflammation of significant morbidity whose recurrence can lead to permanent vision loss. This study was undertaken to inhibit EAAU by inducing tolerance to melanin-associated antigen (MAA) and to investigate the underlying mechanisms responsible for tolerance induction. Intravenous administration of MAA both induced tolerance and inhibited EAAU in Lewis rats. Flow cytometric analysis revealed that the proliferation of lymph node cells in response to antigenic stimulation was drastically reduced in the state of tolerance both in vivo and in vitro. Our results from co-culture experiments demonstrated that intravenous administration of MAA led to the generation of T-regulatory cells that suppress T-cell proliferative responses and induce tolerance. Expression levels of both interleukin-10 and transforming growth factor-beta2 were elevated whereas reduced levels of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 were detected in tolerance-induced animals. Tolerance was reversed by replenishing these animals with recombinant interleukin-2. Tolerance could be adoptively transferred by removing lymph node cells from tolerance-induced donors and giving them to recipient rats. Interestingly, adoptive transfer of tolerance failed when lymph nodes cells were depleted of CD4(+)CD25(+) T cells. In conclusion, T-cell nonresponsiveness because of active suppression mediated by T-regulatory cells facilitates the development of tolerance to MAA in EAAU.
2006-10-24 | CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation.
To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID). ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice. Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice. CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.
2005-07-25 | Differential modulation of allergic eye disease by chronic and acute ascaris infection.
purpose. To assess alterations in allergic ocular responses to nonparasite antigens in an experimental system in which mice were skewed toward a Th2 cytokine profile by helminth infection. methods. Mice were inoculated with Ascaris suum (A. suum) eggs concurrent with ragweed (RW) sensitization (RW/acute) or by repeated inoculation before RW sensitization (RW/chronic). Control subjects were divided into RW, A. suum, and sham-sensitized groups. Animals were RW-challenged in the eye and examined for changes in ocular responses, inflammatory cell infiltrates, and in vitro assessment of cytokines after antigen restimulation. In subsequent experiments, CD4+/CD25+ T regulatory and CD4+/CD25− control T cells were adoptively transferred into mice before ocular challenge. results. RW sensitization and challenge increased ocular symptoms and eosinophil infiltration into the conjunctiva over PBS control eyes. Acute A. suum infection significantly increased RW-induced clinical symptoms and eosinophil infiltrates in the conjunctiva (P = 0.0001) and resulted in the development of anterior uveitis. In contrast, RW/chronic infection provided protection from allergic responses to RW with significantly fewer eosinophils in the eye and reduced eotaxin levels. Transfer of CD4+/CD25+ T cells from RW/chronic mice into RW/acute animals also decreased disease intensity, suggesting that T regulatory cells may contribute to protection from allergic eye disease. conclusions. The current studies suggest acute parasitic infections exacerbate allergic symptoms, whereas chronic infections offer protection and provide possible explanations for the role of parasitic infection in susceptibility and resistance to nonparasite allergens.
other
2026-04-20 | Chronic Eosinophilic Leukemia Presenting as Treatment-Refractory Nodular Scleritis: A Paraneoplastic Autoimmune Syndrome With Multisystem Inflammatory Manifestations.
We report the first documented case of chronic eosinophilic leukemia (CEL) with ETV6-SYK gene rearrangement manifesting as refractory bilateral nodular scleritis within a broader paraneoplastic autoimmune syndrome. A 25-year-old woman with pre-existing Hashimoto's thyroiditis developed progressive bilateral nodular scleritis with anterior uveitis that proved completely refractory to high-dose corticosteroids, methotrexate, and conventional disease-modifying antirheumatic drugs, along with papilledema and granulomatous rosacea, suggesting systemic inflammation. Comprehensive evaluation revealed persistent marked eosinophilia (peak 15,000/μL), prompting hematological investigation, including a bone marrow biopsy and cytogenetic analysis that confirmed CEL harboring the ETV6-SYK fusion oncogene. Recognition of this molecular target enabled precision therapy with fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, combined with adalimumab, a tumor necrosis factor-alpha (TNF-α) inhibitor, resulting in complete and sustained remission of all inflammatory manifestations over 18 months of follow-up. This case underscores the critical importance of maintaining high clinical suspicion for paraneoplastic autoimmune syndromes in patients with treatment-refractory inflammatory conditions, particularly when accompanied by atypical systemic or unexplained laboratory findings, and demonstrates that molecularly targeted precision medicine approaches can transform treatment outcomes in complex paraneoplastic rheumatic disorders.
2026-02-23 | Viral triggers and genetic predisposition in ocular autoimmunity: unraveling the breakdown of immune privilege and advancing targeted therapeutics.
The eye maintains vision through a distinctive immune privilege, utilizing physical barriers and active immunosuppression mediated by molecules such as FasL and PD-L1, as well as cells, including regulatory T cells and RPE cells. The emergence of sight-threatening immune-mediated ocular diseases, including non-infectious uveitis, signifies a significant disruption of this tolerance. This review analyzes the role of viral triggers and genetic predisposition in inducing immunological failure, while emphasizing the development of targeted therapeutic strategies. Viruses induce autoimmunity through molecular mimicry (Rotavirus peptides cross-reacting with retinal S-antigen), bystander activation, and active immune suppression (CMV inhibiting RPE cell IDO1 activity). HLA alleles, especially HLA-A29 (Birdshot Chorioretinopathy) and HLA-B27 (acute anterior uveitis), as well as non-MHC genes like NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and AIRE, greatly increase the risk of genetic disorders. Treatment is progressing towards precision medicine, with targeted biologics like the IL-6 receptor inhibitor Tocilizumab being key strategies. Moreover, AAV-mediated gene therapy that expresses immunosuppressive molecules such as HLA-G demonstrates promise for the restoration of long-term tolerance in preclinical models, facilitating the development of advanced future strategies.
2025-04-18 | The clinical safety landscape for ocular AAV gene therapies: A systematic review and meta-analysis.
Adeno-associated virus (AAV) gene therapy is a promising approach for treating ocular monogenic or acquired diseases, though immunogenicity and safety remain critical considerations. We conducted a systematic review of 120 trials and 32 publications to assess immune responses across different delivery routes. Intravitreal administration was associated with higher rates of anterior uveitis (43.06% vs. 10.22%) and intermediate/posterior uveitis (40.36% vs. 6.18%) compared to subretinal delivery. Engineered AAV capsids, used exclusively in intravitreal studies, showed no significant difference in either type of uveitis incidence compared to natural serotypes. Prophylactic immunosuppression (PI) did not affect ocular or systemic immune responses in subretinal delivery, but significantly reduced systemic immune responses in intravitreal administration. These findings underscore the potential of PI to mitigate systemic immune responses in intravitreal AAV therapy. This review should help guide the choice of routes of administration and immunosuppression strategies, and highlights current trends in ocular AAV gene therapy.
2011-11-03 | Ocular gene delivery using lentiviral vectors
Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable for gene delivery in ophthalmic diseases, including high expression, consistent targeting of various post-mitotic ocular cells in vivo and a paucity of associated intraocular inflammation, all contributing to their ability to mediate efficient and stable intraocular gene transfer. In this review, the intraocular tropisms and therapeutic applications of both primate and non-primate lentiviral vectors, and how the unique features of the eye influence these, are discussed. The feasibility of therapeutic targeting using these vectors in animal models of both anterior and posterior ophthalmic disorders has been established, and has, in combination with substantial progress in enhancing lentiviral vector bio-safety over the past two decades, paved the way for the first human ophthalmic clinical trials using lentivirus-based gene transfer vectors.
2008-06-26 | Lentiviral-vector-mediated expression of murine IL-1 receptor antagonist or IL-10 reduces the severity of endotoxin-induced uveitis
Uveitis is a sight threatening inflammatory disorder that remains a significant cause of visual loss. We investigated lentiviral gene delivery of interleukin 1 receptor antagonist (IL-1ra) or interleukin (IL)-10 to ameliorate murine endotoxin-induced uveitis (EIU). An human immunodeficiency virus-1-based vector containing the mIL-1ra or mIL-10 cDNA demonstrated high expression of biologically active cytokine. Following administration of Lenti.GFP into the anterior chamber, transgene expression was observed in corneal endothelial cells, trabecular meshwork and iris cells. To treat EIU, mice were injected with Lenti.IL-1ra, Lenti.IL-10 or a combination of these. EIU was induced 14 days after vector administration and mice were culled 12 h following disease induction. Lenti.IL-1ra or Lenti.IL-10-treated eyes showed significantly lower mean inflammatory cell counts in the anterior and posterior chambers compared with controls. The aqueous total protein content was also significantly lower in treated eyes, demonstrating better preservation of the blood-ocular barrier. Furthermore, the treated eyes showed less in vivo fluorescein leakage from inner retinal vessels compared with controls. The combination of both IL-1ra and IL-10 had no additive effect. Thus, lentiviral gene delivery of IL-1ra or IL-10 significantly reduces the severity of experimental uveitis, suggesting that lentiviral-mediated expression of immunomodulatory genes in the anterior chamber offers an opportunity to treat uveitis.
small molecules
2026-09-28 | Fibrinous Acute Anterior Uveitis as a Manifestation of Poorly Controlled Type 2 Diabetes Mellitus
A male patient with diabetes presented with acute painful red eye associated with diminution of vision in the left eye. Ocular examination revealed severe fibrinous anterior uveitis: a dense anterior chamber reaction, with posterior synechiae. Infectious and autoimmune etiologies were excluded with thorough investigations, and uncontrolled hyperglycemia was attributed as likely precipitating factor. The patient responded rapidly to intensive topical corticosteroids and optimization of systemic diabetic therapy. This case highlights the association of poorly controlled diabetes mellitus with severe intraocular inflammation and emphasizes the importance of clinicians considering diabetes mellitus-associated anterior uveitis in patients with significant metabolic dysregulation.
2026-09-11 | Topical versus oral antiviral therapy for cytomegalovirus anterior uveitis: a multicenter study in Taiwan.
To compare topical and oral antiviral therapies for cytomegalovirus (CMV) anterior uveitis (AU) in terms of efficacy. This retrospective study included 240 patients with CMV AU who received treatment at Chang Gung Memorial Hospital between 2007 and 2019. Their diagnoses were confirmed through aqueous polymerase chain reaction. The mean follow-up duration was 4.0 ± 3.1 years. The proportion of patients with an acute uveitis course, defined as no anti-CMV medication use beyond 3 months after diagnosis, was higher in patients initially treated with oral valganciclovir than in those initially treated with topical ganciclovir (40.0% vs. 15.7%; p = 0.038). Patients initially treated with topical ganciclovir plus oral valganciclovir were least likely to develop chronic disease (combined therapy vs. topical therapy vs. oral therapy: 5.0% vs. 39.3% vs. 20.0%; p = 0.007). Within 3 years, the risk of glaucoma surgery or laser intervention was lower in the acute group compared with the chronic (odds ratio [OR]: 0.25, 95% confidence interval [CI]: 0.08-0.82) and recurrent (OR: 0.32, 95% CI: 0.11-0.92) groups. The risk of corneal transplantation was lower in both the acute and chronic groups compared with the recurrent group (OR: 0.17, 95% CI: 0.05-0.56; and OR: 0.28, 95% CI: 0.09-0.86, respectively). Compared with topical ganciclovir, oral valganciclovir is associated with a lower risk of recurrent and chronic CMV AU. Chronic and recurrent disease are associated with increased risk of glaucoma requiring intervention, and recurrent disease carries an additional risk of corneal decompensation.
2026-08-24 | Bilateral anterior and intermediate uveitis associated with parvovirus B19 infection in a pediatric patient: A case report
To describe a rare case of bilateral anterior and intermediate uveitis associated with parvovirus B19 infection in a pediatric patient and highlight diagnostic and therapeutic considerations. A 5-year-old boy presented with bilateral ocular pain, conjunctival hyperemia, and decreased visual acuity one week after hospitalization for systemic parvovirus B19 infection. Laboratory investigations excluded other infectious and autoimmune causes. Ophthalmologic examination revealed bilateral anterior chamber inflammation and vitritis. B-scan ultrasonography confirmed vitreous opacities. Polymerase chain reaction (PCR) analysis of anterior chamber fluid was performed to determine the etiologic agent. PCR testing detected parvovirus B19 DNA in the anterior chamber fluid, confirming the diagnosis. Initial treatment with intensive topical corticosteroids and cycloplegic agents failed to control inflammation. Subconjunctival dexamethasone injection resulted in rapid resolution of ocular inflammation and complete recovery of visual acuity. Parvovirus B19 should be considered in pediatric patients presenting with bilateral uveitis following systemic viral symptoms.
2026-07-30 | AYURVEDIC MANAGEMENT OF ACUTE ANTERIOR UVEITIS (PITTAJA ADHIMANTHA): A CASE REPORT
Introduction: Uveitis is an inflammatory disorder of the vascular layer of the eyeball and accounts for approximately 10% of blindness. Anterior uveitis denotes inflammation of the iris and/or the anterior part of the ciliary body and is characterized by pain, photophobia, ciliary congestion, blurred vision and keratic precipitates; if not treated promptly it can cause complications such as glaucoma, cataract, cystoid macular oedema and retinal detachment. Case presentation: A 40‑year‑old male presented with bilateral ocular pain, redness, watering, photophobia and blurred vision for 4–5 days, diagnosed as anterior uveitis and correlated with Pittaja Adhimantha according to Ayurveda. He was treated with Jalaukavacharana (leech therapy) on day 1 and day 7 along with internal medications: Gokshuradi Guggulu 250 mg – 2 tablets twice daily for 7 days, a ghrita preparation 3 g twice daily for 7 days, Saptamrita Lauha 1 tablet twice daily for 15 days and Triphala Avaleha 1 teaspoon once daily for 15 days. Results: By the third day of treatment, ocular pain, redness, photophobia, watering and blurring of vision had reduced by about 50% compared with baseline, and by the seventh day the patient became completely asymptomatic. Conclusion: The combination of Jalaukavacharana with internal Pitta‑shamana medicines including Gokshuradi Guggulu, ghrita, Saptamrita Lauha and Triphala Avaleha proved effective in this case of acute anterior uveitis (Pittaja Adhimantha), suggesting a useful Ayurvedic alternative or adjunct to steroid‑based management.
2026-07-19 | AYURVEDIC MANAGEMENT OF RECURRENT ANTERIOR UVEITIS (RAKTAJA AD-HIMANTHA): A CASE STUDY
A 40-year-old male patient came to the Ophthalmology OPD in December 2025 with complaints of redness, water-ing (epiphora), blurred vision and pain in the left eye for the last 5-7 days. On detailed history-taking, the patient reported that similar episodes had recurred every 15-20 days over the past year, significantly affecting daily functioning. Based on clinical signs, symptoms, and Ayurvedic diagnostic pa-rameters, the condition was diagnosed as Raktaja Adhimantha. The patient was managed with an Ayurvedic thera-peutic protocol comprising Jalaukavacharana (leech therapy), Netraseka, and oral Ayurvedic medicines. The symp-toms resolved within 21 days, and the anterior chamber findings returned to normal after almost one month. Oral medication was continued for two months. Patient remains symptom-free for four months. Thereafter, no recur-rence was noticed till May 2026. Raktamokshana, along with netraseka and oral medication, is effective in recur-rent anterior uveitis.
proteins
2026-08-27 | IVIG-associated anterior uveitis resolving after switch to subcutaneous immunoglobulin.
Intravenous immunoglobulin (IVIG) therapy can occasionally induce unexpected inflammatory complications. A case report and literature review. We report a patient with hypogammaglobulinemia and systemic autoimmunity who developed reproducible unilateral anterior uveitis following IVIG administration across multiple formulations. Discontinuation of IVIG resolved the ocular inflammation but caused underlying disease exacerbation. Transition to facilitated subcutaneous immunoglobulin (SCIG) achieved stable serum IgG levels and maintained complete ocular and systemic remission over a four-year follow-up period. This case demonstrates peak-driven immune activation as a plausible mechanism for IVIG-induced uveitis and highlights SCIG as a safe, effective therapeutic alternative that bypasses rapid peak IgG dynamics while preserving immune protection.
2026-08-24 | Local therapy in uveitis: Current concepts and emerging strategies.
Local therapy plays a pivotal role in the management of noninfectious uveitis, providing targeted drug delivery with reduced systemic adverse effects. Advances in corticosteroid formulations and delivery routes have significantly improved therapeutic outcomes. Topical corticosteroids remain first-line for anterior uveitis, while periocular and intravitreal injections such as triamcinolone acetonide and dexamethasone implants (Ozurdex®) are effective for intermediate and posterior disease. Long-acting fluocinolone acetonide implants (Retisert®, Yutiq®) offer sustained control for chronic or recurrent cases, though ocular hypertension and cataract formation are common. The introduction of suprachoroidal corticosteroid delivery (Xipere®) allows precise posterior segment targeting with fewer anterior complications. Nonsteroidal intravitreal agents, including methotrexate and sirolimus, serve as steroid-sparing options, and topical immunomodulators such as cyclosporine and tacrolimus can be rarely used in chronic anterior uveitis. Emerging modalities like intravitreal biologics, nanocarrier systems, and gene-based delivery hold promise for long-term disease modulation. A tailored, evidence-based approach to local therapy can optimize inflammation control and visual outcomes in uveitis management.
2026-06-16 | Supramolecular peptide hydrogels for the treatment of ocular diseases: from tissue replacements to drug delivery systems.
Supramolecular peptide hydrogels (SPHs), a unique class of dynamic three-dimensional networks formed by self-assembly of peptides, have demonstrated strong potential for ocular tissue replacement and drug delivery in ophthalmic applications. On the one hand, their mechanical and physiochemical properties can be precisely tailored via rational design of peptides to emulate native ocular tissues. On the other hand, the intrinsic dynamic features of SPHs enable efficient encapsulation of commercial drugs and incorporation of stimuli-responsive or targeting moieties, which in turn facilitate ocular barrier penetration and enhance therapeutic efficacy. In this review, we systematically summarize recent advances of the use of SPHs in ocular disease treatment, focusing on their design principles and two key application aspects: ocular tissue substitutes (for vitreous and corneal repair) and drug delivery systems targeting prevalent ocular pathologies, including dry eye disease, corneal neovascularization, bacterial keratitis, anterior uveitis, diabetic retinopathy, and age-related macular degeneration. These findings highlight the promising potential of SPHs as next-generation biomaterials for precision ophthalmic therapy.
2026-04-22 | Concurrent herpetic hypertensive anterior uveitis and cytomegalovirus retinitis in a non-HIV patient with melanoma differentiation-associated gene-5 dermatomyositis: intravenous immunoglobulin comes to the rescue.
Melanoma differentiation-associated gene 5 dermatomyositis (MDA-5 DM) is a rare subtype of dermatomyositis. Cytomegalovirus (CMV) retinitis is an opportunistic ocular infection that has historically been linked to HIV infection. Herpes simplex virus (HSV) uveitis is caused by the reactivation of the varicella-zoster virus. We present the case of a 69-year-old woman diagnosed with aggressive MDA-5 DM associated with interstitial lung disease, who received multiple immunosuppressive therapies and subsequently developed left eye CMV retinitis and right eye acute herpetic, hypertensive, anterior uveitis with dendritic keratitis. After the diagnosis of MDA-5 DM, she was treated with glucocorticoids (GC), followed by rituximab and triple therapy (cyclosporine, cyclophosphamide, and GC); however, she did not improve and multiple adverse effects occurred. The patient then started tofacitinib (TOF) and improved. While being on TOF, she developed right eye acute herpetic, hypertensive, anterior uveitis, followed by left eye CMV retinitis. TOF was stopped, and the patient started oral acyclovir and intravenous and intravitreal ganciclovir, which was later changed to maintenance therapy with oral valganciclovir. Cyclical intravenous immunoglobulin (IVIG) administration was started, resulting in an overall improvement in disease activity associated with MDA-5 DM. This case underscores the uncommon link between CMV retinitis in a non-HIV patient and HSV anterior uveitis in a patient undergoing immunosuppressive therapy and the challenge of treating MDA-5 DM with IVIG, which led to favorable results.
2026-01-21 | Successful goniosynechialysis for secondary angle-closure glaucoma after ocular jellyfish sting.
Little is known about the ocular effects of jellyfish stings and their optimal management. We report the case of a 25-year-old fisherman that presented to the Emergency Department with a painful red eye, photophobia and blurred vision 24 hours after a jellyfish sting in his right eye (RE), that was projected from a fishing net. Visual acuity of the RE was 20/80. Examination of the RE revealed anterior uveitis, areas of iris stromal atrophy, 360° peripheral anterior synechiae (PAS) and intraocular pressure (IOP) of 45 mmHg. Left eye was normal. Anterior segment inflammation resolved with topical anti-inflammatory therapy, but IOP remained uncontrolled despite maximal hypotensive therapy. Two months later, goniosynechialysis was performed and restored aqueous outflow, achieving long-term IOP control. The surgery was uneventful, and PAS were separated from the angle using micro-forceps. This case highlights important ocular findings - acute iris stromal atrophy, extensive PAS and severe ocular hypertension - secondary to jellyfish toxins, raising awareness to the rare entity of jellyfish stings. Early recognition and prompt surgical intervention may be sight-saving, in cases of ocular jellyfish stings, preventing the development of secondary chronic angle-closure glaucoma.
antibodies
2026-09-22 | Advances in tumor necrosis factor-α inhibitors for the treatment of juvenile idiopathic arthritis-associated uveitis.
Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a common and sight-threatening extra-articular manifestation of juvenile idiopathic arthritis, typically presenting as chronic noninfectious anterior uveitis. Its early symptoms are often insidious, and delayed detection and treatment may lead to cataract, glaucoma, macular edema, and irreversible visual impairment. Conventional treatment is based on glucocorticoids and immunosuppressants; however, some children continue to experience inadequate efficacy, glucocorticoid dependence, drug intolerance, or adverse events. In recent years, substantial progress has been made in the use of biologics for JIA-U. Among them, tumor necrosis factor-α inhibitors, particularly adalimumab, have shown potential for controlling ocular inflammation, reducing glucocorticoid exposure, and improving visual outcomes, thereby offering a new therapeutic avenue for patients with JIA-U. Although TNF-α inhibitors have become an important component of systemic therapy for JIA-U, optimal dosing, long-term maintenance, tapering, and the timing of discontinuation require further investigation. Additional prospective, disease-specific pediatric studies are needed to define the optimal timing of TNF-α inhibitor initiation, precise dose-adjustment strategies, and long-term safety management, thereby advancing individualized and precision treatment for JIA-U.
2026-09-18 | Biologic Therapy in Refractory Non-Infectious Uveitis: An Analysis of 60 Cases at a Tertiary Eye Care Centre from South India.
To evaluate the effectiveness and safety of biologic therapy in patients with refractory non-infectious uveitis (NIU) in a real-world clinical setting. A retrospective observational study was conducted at a tertiary eye care centre in South India between 2022 and 2025. Patients diagnosed with NIU, who were not responding to conventional treatment and had received biologics during this period, were included. Demographic details, anatomical classification, etiological diagnosis, type of biologic used, treatment duration, clinical outcomes, and adverse events were analysed. A total of 60 patients with refractory NIU receiving biologic therapy were included. The mean age at biologic initiation was 23.1 ± 13.7 years, comprising 27 (45%) paediatric and 33 (55%) adults. The mean duration of uveitis prior to biologic initiation was 34.48 ± 52.36 months. Anterior uveitis was the most common (40%). Autoimmune etiologies predominated, with juvenile idiopathic arthritis-associated uveitis (28.3%), HLA-B27-associated uveitis (23.3%), and Behçet disease (20%). Adalimumab was the most frequently used biologic agent (88.3%) followed by Infliximab (5%), golimumab (3.3%) and tocilizumab (3.3%). Biologic therapy resulted in significant control of intraocular inflammation (p < 0.0001). Visual acuity remained stable throughout the follow-up. Treatment modification was required in 7 patients (11.7%). Side effects were observed in 3 (5%) patients, 2 (3.3%) showed inadequate response and 2 patients (3.3%) discontinued biologics due to financial constraints. Biologic therapy is an effective and safe therapy for refractory non-infectious uveitis across all age-groups and etiologies. Early escalation to biologics may help arrest long-term cumulative inflammatory damage and preserve visual function by sustained inflammatory control.
2026-09-10 | Biologic and targeted synthetic therapies in ankylosing spondylitis: a pharmacological review.
Ankylosing spondylitis (AS) is a prototypical axial spondyloarthritis (axSpA) defined by chronic inflammatory back pain, progressive spinal stiffness, and frequent extra-articular manifestations such as acute anterior uveitis (21%-33%), inflammatory bowel disease (5%-10%), and psoriasis (4%-13%). Management has shifted from non-steroidal anti-inflammatory drugs (NSAIDs) to highly targeted biologic and synthetic disease-modifying antirheumatic drugs (DMARDs). This comprehensive review focuses on the current evidence for biologic and targeted synthetic therapeutics in the management of AS, emphasizing mechanisms of action, regulatory approvals, dosing regimens, and clinical efficacy. Three major therapeutic classes are identified: two biologic DMARD classes, comprising tumor necrosis factor-alpha (TNF-α) inhibitors and interleukin-17 (IL-17) inhibitors, and the targeted synthetic DMARDs, namely, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, certolizumab pegol) typically achieve Assessment of Spondyloarthritis International Society 40% improvement (ASAS40) rates of 40%-58% at 12-24 weeks versus 13%-24% with placebo, and maintain clinical benefit in many patients over 5-8 years. IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, brodalumab, netakimab) yield broadly similar ASAS40 responses (30%-50% versus 10%-20% placebo) and are particularly useful in patients with concomitant psoriasis with substantially reduced risk of tuberculosis reactivation. JAK inhibitors (tofacitinib, upadacitinib) represent the newest class, offering oral administration with ASAS40 responses of 40%-52% versus 13%-26% for placebo in both biologic-naïve and biologic-experienced AS, though cardiovascular safety considerations necessitate careful patient selection. Therapeutic selection should consider comorbidities (uveitis favors TNF monoclonal antibodies; psoriasis favors IL-17 inhibitors), safety profile, route of administration, and sequencing after non-steroidal anti-inflammatory drug failure. Understanding these pharmacological distinctions enables personalized therapeutic decisions based on the specific molecular pathology and risk profile of the individual patient.
2026-08-29 | Comparison of the Risk of Acute Anterior Uveitis Flare Between Adalimumab and Subcutaneous Infliximab in Patients with Radiographic Axial Spondyloarthritis and Prior Acute Anterior Uveitis: A Randomized Controlled Trial.
Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation of radiographic axial spondyloarthritis (r-axSpA) and is an important consideration when selecting biological therapy. Although adalimumab (ADA) and infliximab are commonly used in patients with r-axSpA and AAU, direct comparative evidence, particularly between ADA and subcutaneous infliximab (IFX-SC), remains limited. The objective of this study was to compare the risk of AAU flare between ADA and IFX-SC in patients with r-axSpA and a history of AAU. This multicenter, head-to-head, randomized, open-label trial enrolled patients with r-axSpA and a documented AAU event within the preceding 2 years. Participants were randomly assigned (1:1) to receive ADA (40 mg every 2 weeks) or IFX-SC (intravenous 5 mg/kg induction followed by subcutaneous 120 mg every 2 weeks) and were followed for 48 weeks. The primary endpoint was AAU flare occurrence. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Secondary endpoints included changes in best-corrected visual acuity (BCVA), r-axSpA disease activity and functional indices, and safety outcomes. Fifty-six patients were randomized (ADA, n = 28; IFX-SC, n = 28). During follow-up, one AAU flare episode occurred in each group. The adjusted HR of IFX-SC (vs ADA) for an AAU flare was 0.496 (95% confidence interval 0.025-9.768, p = 0.645). No significant differences in secondary endpoints were observed between groups (right BCVA, p = 0.622; left BCVA, p = 0.306; Axial Spondyloarthritis Disease Activity Score, p = 0.293; Bath Ankylosing Spondylitis Disease Activity Index, p = 0.262; Bath Ankylosing Spondylitis Functional Index, p = 0.307). Adverse events were similar in frequency and severity, with no new safety signals identified. No statistically significant differences in AAU flare risk or secondary ocular and rheumatologic outcomes were observed between ADA and IFX-SC over 48 weeks in patients with r-axSpA and prior AAU. These findings suggest that IFX-SC may represent a potential alternative to ADA for AAU flare prevention as well as disease activity control in this population. Clinical Research Information Service (CRIS), Republic of Korea; KCT0007239.
2026-07-18 | Treatment of spontaneous hyphema in Fuch's heterochromic iridocyclitis with intravitreal anti-VEGF ranibizumab.
Fuch's heterochromic iridocyclitis (FHI) is a unilateral ocular condition characterised by low-grade anterior uveitis. Although the underlying aetiology remains unclear, proposed triggers include infections, autoimmune mechanisms and genetic predisposition. Amsler's sign is a recognised complication of FHI whereby patients develop spontaneous hyphaema that is often self-limiting. Current management of FHI focuses on managing complications such as raised intraocular pressures (IOPs), secondary glaucoma and formation of cataracts rather than the inflammation itself. In this case report, we present a patient with FHI complicated by spontaneous hyphaema and acute-on-chronic ocular hypertension refractory to medical therapy. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) ranibizumab was used, which achieved rapid resolution of hyphaema with resultant reduction in IOP. Subsequent trabeculectomy was performed for definitive control of persistent chronic ocular hypertension. This case highlights anti-VEGF therapy as a potential adjunctive strategy in selected patients presenting with similar clinical challenges.
cell therapies
2025-04-03 | Human umbilical cord-derived mesenchymal stem/stromal cells via suprachoroidal injection: A novel approach for experimental uveitis treatment
Uveitis is a group of vision-threatening inflammatory diseases, and current treatment options are mainly limited to corticosteroids, which often have side effects and do not address the underlying immune dysregulation. Mesenchymal stem/stromal cells cultivated in vitro have gained attention for their immune-regulating, neurotrophic, and tissue-regenerative properties, making them a promising candidate for treating uveitis. This study investigates the safety and efficacy of human umbilical cord derived mesenchymal stem/stromal cells (HUMSCs) combined with a novel suprachoroidal microinjector for targeted delivery in a rabbit model of experimental uveitis (EU). No significant clinical or histological changes were observed following HUMSCs injection in normal Chinichilla rabbit eyes. In the EU model, treatment with HUMSCs and triamcinolone acetonide (TA) significantly alleviated uveitis symptoms compared to phosphate-buffered saline, with notable improvements in anterior chamber inflammation and vitreous opacity scores. Both treatments also reduced the levels of inflammatory cytokines (TNF-α, VEGF, MIP-1α, IL-17A, bFGF) in the aqueous humor. Histological and immunofluorescence analyses showed decreased inflammatory cell infiltration and microglial activation. Additionally, RNA sequencing revealed that HUMSCs injection downregulated key genes in the Th17 differentiation pathway, which plays a critical role in the pathogenesis of EU. These findings establish the safety and efficacy of suprachoroidal injection of HUMSCs, highlighting their potential as an effective, targeted therapeutic approach for uveitis, with results comparable to TA.
2018-03-13 | Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?
Purpose of review The intestinal microbiome is thought to play a role in the pathogenesis of inflammatory bowel disease (IBD). There are many shared clinical manifestations between IBD and spondyloarthritis (SpA), of which the most common are peripheral arthritis and uveitis. Clinical overlap along with similar genetics between these diseases suggests a possible shared pathogenetic mechanism, which might center on the intestinal microbiota. In this review, we discuss the available evidence that SpA is a microbiome-driven disease and indicate how SpA-associated uveitis could be tied to gut dysbiosis. We conclude by discussing different treatment paradigms targeting the intestinal microbiome for SpA. Recent findings Recent studies support the growing evidence of the intestinal microbiome as a crucial player in SpA disease pathogenesis. There is emerging evidence that the gut microbiome may play a causative role in uveitis. Summary The field is beginning to discover a new level of understanding how the intestinal microbiome is involved in SpA. Treatment methods to alter intestinal microbiota to treat SpA-related diseases are still in its infancy.
2008-11-17 | Tolerance to melanin-associated antigen in autoimmune uveitis is mediated by CD4+CD25+ T-regulatory cells.
Experimental autoimmune anterior uveitis (EAAU) serves as an animal model for human idiopathic AU, the most common form of intraocular inflammation of significant morbidity whose recurrence can lead to permanent vision loss. This study was undertaken to inhibit EAAU by inducing tolerance to melanin-associated antigen (MAA) and to investigate the underlying mechanisms responsible for tolerance induction. Intravenous administration of MAA both induced tolerance and inhibited EAAU in Lewis rats. Flow cytometric analysis revealed that the proliferation of lymph node cells in response to antigenic stimulation was drastically reduced in the state of tolerance both in vivo and in vitro. Our results from co-culture experiments demonstrated that intravenous administration of MAA led to the generation of T-regulatory cells that suppress T-cell proliferative responses and induce tolerance. Expression levels of both interleukin-10 and transforming growth factor-beta2 were elevated whereas reduced levels of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 were detected in tolerance-induced animals. Tolerance was reversed by replenishing these animals with recombinant interleukin-2. Tolerance could be adoptively transferred by removing lymph node cells from tolerance-induced donors and giving them to recipient rats. Interestingly, adoptive transfer of tolerance failed when lymph nodes cells were depleted of CD4(+)CD25(+) T cells. In conclusion, T-cell nonresponsiveness because of active suppression mediated by T-regulatory cells facilitates the development of tolerance to MAA in EAAU.
2006-10-24 | CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation.
To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID). ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice. Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice. CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.
2005-07-25 | Differential modulation of allergic eye disease by chronic and acute ascaris infection.
purpose. To assess alterations in allergic ocular responses to nonparasite antigens in an experimental system in which mice were skewed toward a Th2 cytokine profile by helminth infection. methods. Mice were inoculated with Ascaris suum (A. suum) eggs concurrent with ragweed (RW) sensitization (RW/acute) or by repeated inoculation before RW sensitization (RW/chronic). Control subjects were divided into RW, A. suum, and sham-sensitized groups. Animals were RW-challenged in the eye and examined for changes in ocular responses, inflammatory cell infiltrates, and in vitro assessment of cytokines after antigen restimulation. In subsequent experiments, CD4+/CD25+ T regulatory and CD4+/CD25− control T cells were adoptively transferred into mice before ocular challenge. results. RW sensitization and challenge increased ocular symptoms and eosinophil infiltration into the conjunctiva over PBS control eyes. Acute A. suum infection significantly increased RW-induced clinical symptoms and eosinophil infiltrates in the conjunctiva (P = 0.0001) and resulted in the development of anterior uveitis. In contrast, RW/chronic infection provided protection from allergic responses to RW with significantly fewer eosinophils in the eye and reduced eotaxin levels. Transfer of CD4+/CD25+ T cells from RW/chronic mice into RW/acute animals also decreased disease intensity, suggesting that T regulatory cells may contribute to protection from allergic eye disease. conclusions. The current studies suggest acute parasitic infections exacerbate allergic symptoms, whereas chronic infections offer protection and provide possible explanations for the role of parasitic infection in susceptibility and resistance to nonparasite allergens.
other
2026-04-20 | Chronic Eosinophilic Leukemia Presenting as Treatment-Refractory Nodular Scleritis: A Paraneoplastic Autoimmune Syndrome With Multisystem Inflammatory Manifestations.
We report the first documented case of chronic eosinophilic leukemia (CEL) with ETV6-SYK gene rearrangement manifesting as refractory bilateral nodular scleritis within a broader paraneoplastic autoimmune syndrome. A 25-year-old woman with pre-existing Hashimoto's thyroiditis developed progressive bilateral nodular scleritis with anterior uveitis that proved completely refractory to high-dose corticosteroids, methotrexate, and conventional disease-modifying antirheumatic drugs, along with papilledema and granulomatous rosacea, suggesting systemic inflammation. Comprehensive evaluation revealed persistent marked eosinophilia (peak 15,000/μL), prompting hematological investigation, including a bone marrow biopsy and cytogenetic analysis that confirmed CEL harboring the ETV6-SYK fusion oncogene. Recognition of this molecular target enabled precision therapy with fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, combined with adalimumab, a tumor necrosis factor-alpha (TNF-α) inhibitor, resulting in complete and sustained remission of all inflammatory manifestations over 18 months of follow-up. This case underscores the critical importance of maintaining high clinical suspicion for paraneoplastic autoimmune syndromes in patients with treatment-refractory inflammatory conditions, particularly when accompanied by atypical systemic or unexplained laboratory findings, and demonstrates that molecularly targeted precision medicine approaches can transform treatment outcomes in complex paraneoplastic rheumatic disorders.
2026-02-23 | Viral triggers and genetic predisposition in ocular autoimmunity: unraveling the breakdown of immune privilege and advancing targeted therapeutics.
The eye maintains vision through a distinctive immune privilege, utilizing physical barriers and active immunosuppression mediated by molecules such as FasL and PD-L1, as well as cells, including regulatory T cells and RPE cells. The emergence of sight-threatening immune-mediated ocular diseases, including non-infectious uveitis, signifies a significant disruption of this tolerance. This review analyzes the role of viral triggers and genetic predisposition in inducing immunological failure, while emphasizing the development of targeted therapeutic strategies. Viruses induce autoimmunity through molecular mimicry (Rotavirus peptides cross-reacting with retinal S-antigen), bystander activation, and active immune suppression (CMV inhibiting RPE cell IDO1 activity). HLA alleles, especially HLA-A29 (Birdshot Chorioretinopathy) and HLA-B27 (acute anterior uveitis), as well as non-MHC genes like NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and AIRE, greatly increase the risk of genetic disorders. Treatment is progressing towards precision medicine, with targeted biologics like the IL-6 receptor inhibitor Tocilizumab being key strategies. Moreover, AAV-mediated gene therapy that expresses immunosuppressive molecules such as HLA-G demonstrates promise for the restoration of long-term tolerance in preclinical models, facilitating the development of advanced future strategies.
2025-04-18 | The clinical safety landscape for ocular AAV gene therapies: A systematic review and meta-analysis.
Adeno-associated virus (AAV) gene therapy is a promising approach for treating ocular monogenic or acquired diseases, though immunogenicity and safety remain critical considerations. We conducted a systematic review of 120 trials and 32 publications to assess immune responses across different delivery routes. Intravitreal administration was associated with higher rates of anterior uveitis (43.06% vs. 10.22%) and intermediate/posterior uveitis (40.36% vs. 6.18%) compared to subretinal delivery. Engineered AAV capsids, used exclusively in intravitreal studies, showed no significant difference in either type of uveitis incidence compared to natural serotypes. Prophylactic immunosuppression (PI) did not affect ocular or systemic immune responses in subretinal delivery, but significantly reduced systemic immune responses in intravitreal administration. These findings underscore the potential of PI to mitigate systemic immune responses in intravitreal AAV therapy. This review should help guide the choice of routes of administration and immunosuppression strategies, and highlights current trends in ocular AAV gene therapy.
2011-11-03 | Ocular gene delivery using lentiviral vectors
Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable for gene delivery in ophthalmic diseases, including high expression, consistent targeting of various post-mitotic ocular cells in vivo and a paucity of associated intraocular inflammation, all contributing to their ability to mediate efficient and stable intraocular gene transfer. In this review, the intraocular tropisms and therapeutic applications of both primate and non-primate lentiviral vectors, and how the unique features of the eye influence these, are discussed. The feasibility of therapeutic targeting using these vectors in animal models of both anterior and posterior ophthalmic disorders has been established, and has, in combination with substantial progress in enhancing lentiviral vector bio-safety over the past two decades, paved the way for the first human ophthalmic clinical trials using lentivirus-based gene transfer vectors.
2008-06-26 | Lentiviral-vector-mediated expression of murine IL-1 receptor antagonist or IL-10 reduces the severity of endotoxin-induced uveitis
Uveitis is a sight threatening inflammatory disorder that remains a significant cause of visual loss. We investigated lentiviral gene delivery of interleukin 1 receptor antagonist (IL-1ra) or interleukin (IL)-10 to ameliorate murine endotoxin-induced uveitis (EIU). An human immunodeficiency virus-1-based vector containing the mIL-1ra or mIL-10 cDNA demonstrated high expression of biologically active cytokine. Following administration of Lenti.GFP into the anterior chamber, transgene expression was observed in corneal endothelial cells, trabecular meshwork and iris cells. To treat EIU, mice were injected with Lenti.IL-1ra, Lenti.IL-10 or a combination of these. EIU was induced 14 days after vector administration and mice were culled 12 h following disease induction. Lenti.IL-1ra or Lenti.IL-10-treated eyes showed significantly lower mean inflammatory cell counts in the anterior and posterior chambers compared with controls. The aqueous total protein content was also significantly lower in treated eyes, demonstrating better preservation of the blood-ocular barrier. Furthermore, the treated eyes showed less in vivo fluorescein leakage from inner retinal vessels compared with controls. The combination of both IL-1ra and IL-10 had no additive effect. Thus, lentiviral gene delivery of IL-1ra or IL-10 significantly reduces the severity of experimental uveitis, suggesting that lentiviral-mediated expression of immunomodulatory genes in the anterior chamber offers an opportunity to treat uveitis.
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Drug Discovery Landscape
2 orphan drug designations for Anterior uveitis.
2 orphan drug designations for Anterior uveitis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
E. Coli heat-shock protein 70 with bovine retinal S-antigen | proteins | EMA | — | Biotech Tools SA |
AI-RSA | small molecules | FDA | — | AutoImmune, Inc. |
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