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
1,264 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:
1,264 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
2026-07-30 | 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.
2026-07-08 | Long-term structural impact and antiviral efficacy of cytomegalovirus anterior uveitis - results from a 10-year ocular inflammation registry.
To evaluate criteria-based long-term structural outcomes and dose-dependent antiviral effects in cytomegalovirus anterior uveitis (CMV AU). From a 10-year ocular inflammation registry comprising 1,404 patients, 79 eyes from 67 patients with PCR-confirmed CMV AU were identified (mean follow-up, 48 ± 38 months). Serial assessments included retinal nerve fiber layer (RNFL) thickness, corneal endothelial cell density (ECCD), and visual field testing. Criteria for manifest glaucoma were defined as RNFL ≤ 75 μm, interocular asymmetry ≥ 15 μm, or visual field defects; manifest ECCD loss as ≥ 20% interocular difference or ECCD ≤ 1500 cells/mm². Initial treatment response (ITR) was defined as IOP normalization and inflammation reduction within 2 weeks. Flare-up rates were compared between high-dose (2% ganciclovir ≥ QID) and low-dose (2% ganciclovir ≤ TID) topical regimens. The mean age was 56.5 ± 15.5 years, and 82.1% had unilateral disease. Median diagnostic delay was 33 months; 20.9% required repeat aqueous taps. ITR was achieved in 87.6%. High-dose topical antivirals reduced flare-ups 2.25-fold vs. low-dose regimens (0.471 vs. 1.058 events/eye-year; relative risk = 0.45). Glaucoma rose from 30.3% to 62.0% and ECCD loss from 27.8% to 57.0% during follow-up. Kaplan-Meier analysis showed a median time of 9 years from symptom-onset to manifest glaucoma. Above-midline KPs were inversely associated with peak IOP on linear regression (p < 0.001). CMV AU poses significant long-term structural risk despite good short-term control. Early criteria-based treatment and high-dose antivirals reduce relapse, while lifelong maintenance is required in eyes with advanced disease.
2026-06-27 | Statin Intensity and the Risk of Noninfectious Uveitis.
To evaluate whether the 5-year risk of incident noninfectious uveitis (NIU) is associated with the intensity of statin therapy in patients with hyperlipidemia. Retrospective, propensity score-matched cohort study. Patients diagnosed with hyperlipidemia within a nationwide federated electronic medical record network (TriNetX). Patients initiating high-, medium-, or low-intensity statin therapy were compared to two mutually exclusive control cohorts: an active comparator control (proton pump inhibitor [PPI] users) and an unexposed control cohort. Patients with prior uveitis or any history of fibrate use were excluded. Each statin intensity cohort underwent 1:1 propensity score matching with both control groups to balance baseline demographics and systemic comorbidities. 5-year hazard ratios (HR) with 95% confidence intervals (CI) for incident overall NIU, anterior uveitis, and posterior/panuveitis. Prior to matching, the study identified 32,434 high-intensity, 16,955 medium-intensity, and 4,843 low-intensity statin users. Following matching, high-intensity statin therapy was associated with a significantly reduced 5-year risk of overall NIU compared to the unexposed control (HR 0.81, 95% CI: 0.69-0.95) with a statistically significant reduction against the active control (HR 0.73, 95% CI: 0.57-0.94). This protective effect was primarily driven by significant reductions in anterior uveitis against both the unexposed control (HR 0.77, 95% CI: 0.65-0.92) and the active control (HR 0.72, 95% CI: 0.55-0.94). Medium-intensity statin therapy yielded a significant risk reduction for overall NIU (HR 0.81, 95% CI: 0.66-0.99) and anterior uveitis (HR 0.84, 95% CI: 0.68-1.03) against the unexposed control but did not reach statistical significance against the active control. Low-intensity statin regimens did not significantly alter the risk of NIU or any anatomical subtype across either comparison group. Negative control outcome analysis demonstrated null associations across all cohorts, supporting the validity of the observed findings. Statin therapy is associated with an intensity-dependent reduction in the 5-year risk of noninfectious uveitis. High-intensity statin regimens confer the most robust and sustained protective benefit, suggesting that higher-potency dosing is necessary to achieve clinically significant modulation of ocular inflammation.
2026-06-22 | Recurrent acute bilateral cicatricial conjunctivitis as an adverse event of systemic adalimumab for rheumatoid arthritis.
Anti-TNF-α therapies, though known for their anti-inflammatory effects, have been associated with paradoxical inflammatory reactions, of which anterior uveitis is the most common. We report a case of recurrent bilateral cicatricial conjunctivitis linked to systemic adalimumab (ADA) treatment in a 66-year-old man with rheumatoid arthritis (RA). The patient experienced worsening bilateral red eyes, blurry vision, and discomfort following each ADA injection. Examination revealed signs of cicatricial inflammation, which responded to corticosteroids but recurred after subsequent ADA doses. Despite these ocular events, adalimumab was continued due to its effective control of systemic RA, with close ophthalmic monitoring. This case suggests a potential direct association between ADA and cicatricial conjunctivitis, a previously undescribed complication. Aggressive topical corticosteroid treatment may allow the continuation of ADA without compromising systemic disease control.
proteins
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.
2025-08-30 | Glucagon-Like Peptide-1 Receptor Agonists and Risk of Uveitis.
Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used for glycemic control in diabetes, may possess anti-inflammatory properties. Understanding their potential protective role against uveitis could provide insights into novel therapeutic strategies. To evaluate whether being prescribed a GLP-1RA is associated with a reduced risk of developing uveitis. This was a retrospective cohort study using electronic health record (EHR) network data from 2006 to 2025. Propensity score matching was applied to control for demographics, smoking status, hypertension, body mass index, hemoglobin A1c, and diabetic retinopathy stage. Data from the US Collaborative Network of TriNetX, a large multicenter EHR platform, were used in this analysis. Included were patients with and without diabetes with prescriptions for GLP-1RAs, metformin, insulin, or sodium-glucose cotransporter 2 inhibitors (SGLT2is). The control groups consisted of patients without prescriptions for each medication. Use of GLP-1RAs, metformin, insulin, or SGLT2is, identified through prescription records. The primary outcome was the incidence of noninfectious uveitis, identified using International Classification of Diseases (ICD) encounter diagnosis codes. Risk ratios (RRs) with 95% CIs were calculated to assess the association between GLP-1RA use and uveitis risk. Analyses included risk of overall uveitis and subtypes such as chorioretinal inflammation, anterior uveitis, panuveitis, and retinal vasculitis. A total of 516 052 patients were included in this study, 258 026 (mean [SD] age, 56.4 [13.7] years; 159 025 female [61.6%]) in the GLP-1RA group and 258 026 (mean [SD] age, 56.4 [14.0] years; 159 374 female [61.8%]) in the control group. The GLP-1RA cohort had a reduced risk of uveitis compared with controls (RR, 0.48; 95% CI, 0.46-0.51). This was consistent among those with type 2 diabetes (RR, 0.54; 95% CI, 0.51-0.58) and those without diabetes (RR, 0.52; 95% CI, 0.46-0.59). Compared with the cohorts taking metformin (RR, 0.58; 95% CI, 0.54-0.62) and insulin (RR, 0.57; 95% CI, 0.54-0.61), GLP-1RA prescriptions were associated with greater protection against uveitis. However, GLP-1RAs were associated with a slightly increased uveitis risk vs SGLT2is (RR, 1.17; 95% CI, 1.04-1.32). SGLT2i prescriptions were also associated with reduced uveitis risk compared with controls (RR, 0.52; 95% CI, 0.48-0.56). This cohort study found that GLP-1RA prescriptions were associated with a lower risk of uveitis compared with controls. These findings suggest potential anti-inflammatory benefits beyond glycemic control, warranting further investigation into their role in ocular inflammatory diseases.
2024-10-25 | Efficacy and tolerability of subcutaneous repository corticotropin injection in refractory ocular inflammatory diseases.
Repository corticotropin injection (RCI) has been suggested to exert immunomodulatory and anti-inflammatory effects in ocular inflammation. The index retrospective study aimed to evaluate the efficacy and tolerability of subcutaneous RCI in patients with active scleritis or uveitis. Medical records of patients who were diagnosed with different types of active scleritis or uveitis and received RCI for more than six months at a tertiary eye center were reviewed. Patient characteristics including age, sex, comorbidities, clinical findings, treatment details, and adverse events were recorded. A total of 17 eyes of 17 patients were included. Median age was 43 years old and 53% of patients were male. Mean treatment duration was 25.4 ± 15.5 months. Indications for RCI therapy were scleritis (7 anterior and 1 posterior) (47.8%), panuveitis (17.4%), retinal vasculitis (17.4%), chronic/recurrent anterior uveitis (13%), and posterior uveitis (4.35%). RCI was initiated at a dose of 40 to 80 units 3 times weekly. Given the adequate control of inflammation, RCI was successfully discontinued in four patients (23.5%). Prior to RCI therapy, 14 (82.3%) patients were on oral prednisone at an average of 10 mg daily (range 2.5-40 mg), and two (11.7%) patients discontinued prednisone immediately before initiating RCI due to side effects. After six months of therapy, the prednisone dose was reduced in four (23.5%) patients to an average of 3 mg daily (range 1-5 mg) and was stopped in eight (53%) patients. Concomitant immunomodulatory therapies (IMTs) included mycophenolate mofetil (23.5%) and methotrexate (23.5%), and adalimumab (23.5%). Ten patients were on IMTs prior to using RCI, and during the course of treatment, IMT was stopped in two patients and reduced in one. Side effects included insomnia (23%), hypertension (11.7%), lower extremity edema (11.7%), hyperglycemia (11.7%), weight gain (11.7%), and infection (5.8%). RCI may be considered as a potential therapy with acceptable tolerability for patients with non-infectious scleritis or uveitis.
antibodies
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.
2026-06-25 | Uveitis in spondyloarthritis: clinical patterns and differences between axial and peripheral forms.
The association between uveitis and spondyloarthritis is well established. However, its characterization across the different types of spondyloarthritis remains limited in the literature. Therefore, this study aimed to perform a comparative characterization of uveitis in the various types of spondyloarthritis. Retrospective observational study that included patients with non-infectious uveitis and spondyloarthritis from a multidisciplinary uveitis clinic. A descriptive analysis was performed across the different subtypes of spondyloarthritis, followed by a comparative analysis regrouping patients into axial and peripheral SpA categories. 163 patients with spondyloarthritis-associated uveitis were included, comprising radiographic axial spondyloarthritis (49%), non-radiographic axial spondyloarthritis (21%), spondyloarthritis associated with inflammatory bowel disease (13%), psoriatic arthritis (12%), and peripheral spondyloarthritis (4%). Anterior uveitis (97%), acute relapsing course (79%), and alternating laterality (47.4%) were predominant in the overall sample. When comparing axial versus peripheral forms, significant differences were observed: intermediate, posterior, and panuveitis locations occurred exclusively in the peripheral forms, which also showed higher frequencies of chronic courses (p < 0.001), bilateralism (p < 0.05), and greater use of systemic therapy (p = 0.05). Regarding this treatment to control uveitis, 28.2% of patients required immunomodulatory therapy (more sulfasalazine in axial forms, and methotrexate in peripheral) and 17.8% required biologic therapy. Biologic discontinuation was higher in peripheral forms (p = 0.059). Variables predicting greater need for systemic therapy included chronic course, bilateralism, higher number of annual episodes, younger age of onset, peripheral joint involvement, and presence of vitritis (all p < 0.05). Acute anterior uveitis constitutes the most frequent pattern in all spondyloarthritis types. However, peripheral forms exhibit a higher prevalence of non-anterior, chronic, and bilateral uveitis, and, additionally, appeared to require greater use of immunomodulatory therapy. Key Points • Understanding and distinguishing the ocular inflammatory processes associated with SpA may have important therapeutic and prognostic implications. • Although acute recurrent anterior uveitis was the most frequent patternacross all SpA subtypes, in the peripheral SpA group (pSpA, IBD-SpA, and PsA) a higher prevalence of intermediate, posterior, panuveitis, chronic course, and bilateral uveitis was observed. • The peripheral SpA group (pSpA, IBD-SpA, and PsA) appeared to require greater use of immunomodulatory drugs (csDMARDs or biologics) for control of the ocular condition, suggesting the need for closer monitoring and tailored therapeutic strategies.
2026-05-27 | Recent updates in human leukocyte antigen B27-associated uveitis.
There has been progressive understanding in etiopathogenesis, clinical presentation, and effective treatment of anterior uveitis (AU) over the years. Sudden onset, symptomatic acute anterior uveitis (AAU) in a young adult, often male, classically arouses suspicion for human leukocyte antigen (HLA) B27-related uveitis. While the ocular presentation is frequently the earliest manifestation, its systemic counterparts within the spectrum, viz., spondyloarthropathies (SpA), including ankylosing spondylitis (AS), reactive arthritis (RA), psoriatic arthritis (PA), and inflammatory bowel disease-associated inflammation, pose greater diagnostic and therapeutic challenges for rheumatologists and internists. This places the ophthalmologist in a uniquely advantageous yet responsible position in initiating etiologic evaluation and facilitating early systemic recognition. Rapid advances in immunology and molecular medicine have significantly expanded the diagnostic and therapeutic landscape of HLA B27-related disease. Emerging insights implicating the gut microbiome, autoinflammatory mechanisms, and innate immune dysregulation have reshaped traditional concepts of pathogenesis. Concurrently, an improved understanding of cytokine networks and immune signaling pathways has led to the development of targeted biologic and synthetic disease-modifying therapies. Given the dynamic, multisystem nature of HLA B27-associated disease and its variable organ involvement, optimal management necessitates close multidisciplinary collaboration among ophthalmologists, rheumatologists, gastroenterologists, and internists. This article briefly explores the evolving concepts of the complex enigma of the HLA B27 molecule and the basis for recent trends in its understanding at the cellular, molecular, biochemical, and clinical levels.
2026-05-23 | Acute tear-film disruption in treatment-naive acute anterior uveitis: A retrospective case-control study.
The study aimed to quantify the acute tear-film disruption in treatment-naive, 1st-onset noninfectious acute anterior uveitis (AAU) and identify independent and modifiable determinants. Retrospective case-control study enrolling 180 AAU eyes and 90 age-/sex-matched healthy controls. Same-day noninvasive tear breakup time (NIBUT), tear meniscus height, Schirmer-I and Ocular Surface Disease Index were extracted. Multivariable linear regression with bootstrap correction determined predictors of shorter NIBUT. Mean NIBUT was 4.7 seconds lower in AAU than controls (5.7 ± 1.5 seconds vs 10.4 ± 1.5 seconds; P < .001); 66% of AAU eyes versus 2% of controls had NIBUT ≤ 5 seconds. Tear meniscus height (-81 μm), Schirmer-I (-5.3 mm) and Ocular Surface Disease Index (+24 points) all worsened (P < .001). Independent reductions in NIBUT: anterior-chamber cells ≥ 2+ (-1.79 seconds), flare ≥ 3+ (-1.23 seconds), concomitant meibomian gland dysfunction (-0.96 seconds) and daily screen time > 8 hours (-0.59 seconds); adjusted R2 = 0.38, optimism-corrected R2 = 0.35. In this proof-of-concept study, 1st-onset AAU was associated with measurable tear-film destabilization driven by intraocular inflammatory load. While these findings suggest a potential role for early ocular-surface protection, effect sizes represent upper-bound estimates requiring confirmation in unscreened populations before routine clinical application.
2026-05-20 | Interface Between Ophthalmology and Rheumatology in Uveitis and Retinal Vasculitis in Adult Patients, When Does Who Need Whom?
BACKGROUND: There is a significant interface between ophthalmology and rheumatology, particularly in uveitis and retinal vasculitis. This will be described in detail here. RESULTS: Analyses of uveitis consultations from university centres in Austria and Germany show that approximately 30% of anterior uveitis cases, 17% of intermediate and posterior uveitis cases, 7% of panuveitis cases, and 20% of retinal vasculitis cases, are associated with an inflammatory rheumatic systemic disease. The most frequent association (30%) is between spondyloarthritis and psoriatic arthritis with anterior uveitis (AAU). In approximately 1.3% of cases of intermediate uveitis, sarcoidosis is present, while in posterior uveitis and panuveitis, Behcet's syndrome (BS) is the most likely cause (2.5% and 12.6%, respectively). Retinal vasculitis is associated with BS in 18% of cases. Easily detectable "red flags" for inflammatory rheumatic diseases and the influence of uveitis on systemic immunomodulatory therapy in rheumatology have been described. For example, in AAU during SPA, monoclonal tumour necrosis factor inhibitors (TNFi) are more effective than etanercept, a fusion protein of the TNF receptor and immunoglobulin Fc segment. IL-17 antagonists and Janus-Kinase (JAK) inhibitors are also able to reduce the risk of uveitis flares, but are less effective than monoclonal TNFi. SUMMARY: Close collaboration between rheumatologists and ophthalmologists is essential, particularly in the treatment of uveitis and retinal vasculitis. Assessment for certain warning signs and determination of specific laboratory parameters are helpful in detecting the association, present in approximately 20% of cases, between uveitis and retinal vasculitis and inflammatory rheumatic systemic diseases, and in referring patients specifically to rheumatology. Conversely, rheumatologists require precise ophthalmological findings and information on treatment response, in order to adjust therapy in a targeted manner or, in cases of ocular symptoms associated with an underlying inflammatory systemic disease, in order to appropriately adapt the therapy to the ocular involvement.
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
2026-02-23 | 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.
2005-12-13 | Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF‐α soluble receptor in uveitis
Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long-lasting expression and secretion of therapeutic proteins. High and long-lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF-alpha soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxin-induced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.
small molecules
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.
2026-07-08 | Long-term structural impact and antiviral efficacy of cytomegalovirus anterior uveitis - results from a 10-year ocular inflammation registry.
To evaluate criteria-based long-term structural outcomes and dose-dependent antiviral effects in cytomegalovirus anterior uveitis (CMV AU). From a 10-year ocular inflammation registry comprising 1,404 patients, 79 eyes from 67 patients with PCR-confirmed CMV AU were identified (mean follow-up, 48 ± 38 months). Serial assessments included retinal nerve fiber layer (RNFL) thickness, corneal endothelial cell density (ECCD), and visual field testing. Criteria for manifest glaucoma were defined as RNFL ≤ 75 μm, interocular asymmetry ≥ 15 μm, or visual field defects; manifest ECCD loss as ≥ 20% interocular difference or ECCD ≤ 1500 cells/mm². Initial treatment response (ITR) was defined as IOP normalization and inflammation reduction within 2 weeks. Flare-up rates were compared between high-dose (2% ganciclovir ≥ QID) and low-dose (2% ganciclovir ≤ TID) topical regimens. The mean age was 56.5 ± 15.5 years, and 82.1% had unilateral disease. Median diagnostic delay was 33 months; 20.9% required repeat aqueous taps. ITR was achieved in 87.6%. High-dose topical antivirals reduced flare-ups 2.25-fold vs. low-dose regimens (0.471 vs. 1.058 events/eye-year; relative risk = 0.45). Glaucoma rose from 30.3% to 62.0% and ECCD loss from 27.8% to 57.0% during follow-up. Kaplan-Meier analysis showed a median time of 9 years from symptom-onset to manifest glaucoma. Above-midline KPs were inversely associated with peak IOP on linear regression (p < 0.001). CMV AU poses significant long-term structural risk despite good short-term control. Early criteria-based treatment and high-dose antivirals reduce relapse, while lifelong maintenance is required in eyes with advanced disease.
2026-06-27 | Statin Intensity and the Risk of Noninfectious Uveitis.
To evaluate whether the 5-year risk of incident noninfectious uveitis (NIU) is associated with the intensity of statin therapy in patients with hyperlipidemia. Retrospective, propensity score-matched cohort study. Patients diagnosed with hyperlipidemia within a nationwide federated electronic medical record network (TriNetX). Patients initiating high-, medium-, or low-intensity statin therapy were compared to two mutually exclusive control cohorts: an active comparator control (proton pump inhibitor [PPI] users) and an unexposed control cohort. Patients with prior uveitis or any history of fibrate use were excluded. Each statin intensity cohort underwent 1:1 propensity score matching with both control groups to balance baseline demographics and systemic comorbidities. 5-year hazard ratios (HR) with 95% confidence intervals (CI) for incident overall NIU, anterior uveitis, and posterior/panuveitis. Prior to matching, the study identified 32,434 high-intensity, 16,955 medium-intensity, and 4,843 low-intensity statin users. Following matching, high-intensity statin therapy was associated with a significantly reduced 5-year risk of overall NIU compared to the unexposed control (HR 0.81, 95% CI: 0.69-0.95) with a statistically significant reduction against the active control (HR 0.73, 95% CI: 0.57-0.94). This protective effect was primarily driven by significant reductions in anterior uveitis against both the unexposed control (HR 0.77, 95% CI: 0.65-0.92) and the active control (HR 0.72, 95% CI: 0.55-0.94). Medium-intensity statin therapy yielded a significant risk reduction for overall NIU (HR 0.81, 95% CI: 0.66-0.99) and anterior uveitis (HR 0.84, 95% CI: 0.68-1.03) against the unexposed control but did not reach statistical significance against the active control. Low-intensity statin regimens did not significantly alter the risk of NIU or any anatomical subtype across either comparison group. Negative control outcome analysis demonstrated null associations across all cohorts, supporting the validity of the observed findings. Statin therapy is associated with an intensity-dependent reduction in the 5-year risk of noninfectious uveitis. High-intensity statin regimens confer the most robust and sustained protective benefit, suggesting that higher-potency dosing is necessary to achieve clinically significant modulation of ocular inflammation.
2026-06-22 | Recurrent acute bilateral cicatricial conjunctivitis as an adverse event of systemic adalimumab for rheumatoid arthritis.
Anti-TNF-α therapies, though known for their anti-inflammatory effects, have been associated with paradoxical inflammatory reactions, of which anterior uveitis is the most common. We report a case of recurrent bilateral cicatricial conjunctivitis linked to systemic adalimumab (ADA) treatment in a 66-year-old man with rheumatoid arthritis (RA). The patient experienced worsening bilateral red eyes, blurry vision, and discomfort following each ADA injection. Examination revealed signs of cicatricial inflammation, which responded to corticosteroids but recurred after subsequent ADA doses. Despite these ocular events, adalimumab was continued due to its effective control of systemic RA, with close ophthalmic monitoring. This case suggests a potential direct association between ADA and cicatricial conjunctivitis, a previously undescribed complication. Aggressive topical corticosteroid treatment may allow the continuation of ADA without compromising systemic disease control.
proteins
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.
2025-08-30 | Glucagon-Like Peptide-1 Receptor Agonists and Risk of Uveitis.
Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used for glycemic control in diabetes, may possess anti-inflammatory properties. Understanding their potential protective role against uveitis could provide insights into novel therapeutic strategies. To evaluate whether being prescribed a GLP-1RA is associated with a reduced risk of developing uveitis. This was a retrospective cohort study using electronic health record (EHR) network data from 2006 to 2025. Propensity score matching was applied to control for demographics, smoking status, hypertension, body mass index, hemoglobin A1c, and diabetic retinopathy stage. Data from the US Collaborative Network of TriNetX, a large multicenter EHR platform, were used in this analysis. Included were patients with and without diabetes with prescriptions for GLP-1RAs, metformin, insulin, or sodium-glucose cotransporter 2 inhibitors (SGLT2is). The control groups consisted of patients without prescriptions for each medication. Use of GLP-1RAs, metformin, insulin, or SGLT2is, identified through prescription records. The primary outcome was the incidence of noninfectious uveitis, identified using International Classification of Diseases (ICD) encounter diagnosis codes. Risk ratios (RRs) with 95% CIs were calculated to assess the association between GLP-1RA use and uveitis risk. Analyses included risk of overall uveitis and subtypes such as chorioretinal inflammation, anterior uveitis, panuveitis, and retinal vasculitis. A total of 516 052 patients were included in this study, 258 026 (mean [SD] age, 56.4 [13.7] years; 159 025 female [61.6%]) in the GLP-1RA group and 258 026 (mean [SD] age, 56.4 [14.0] years; 159 374 female [61.8%]) in the control group. The GLP-1RA cohort had a reduced risk of uveitis compared with controls (RR, 0.48; 95% CI, 0.46-0.51). This was consistent among those with type 2 diabetes (RR, 0.54; 95% CI, 0.51-0.58) and those without diabetes (RR, 0.52; 95% CI, 0.46-0.59). Compared with the cohorts taking metformin (RR, 0.58; 95% CI, 0.54-0.62) and insulin (RR, 0.57; 95% CI, 0.54-0.61), GLP-1RA prescriptions were associated with greater protection against uveitis. However, GLP-1RAs were associated with a slightly increased uveitis risk vs SGLT2is (RR, 1.17; 95% CI, 1.04-1.32). SGLT2i prescriptions were also associated with reduced uveitis risk compared with controls (RR, 0.52; 95% CI, 0.48-0.56). This cohort study found that GLP-1RA prescriptions were associated with a lower risk of uveitis compared with controls. These findings suggest potential anti-inflammatory benefits beyond glycemic control, warranting further investigation into their role in ocular inflammatory diseases.
2024-10-25 | Efficacy and tolerability of subcutaneous repository corticotropin injection in refractory ocular inflammatory diseases.
Repository corticotropin injection (RCI) has been suggested to exert immunomodulatory and anti-inflammatory effects in ocular inflammation. The index retrospective study aimed to evaluate the efficacy and tolerability of subcutaneous RCI in patients with active scleritis or uveitis. Medical records of patients who were diagnosed with different types of active scleritis or uveitis and received RCI for more than six months at a tertiary eye center were reviewed. Patient characteristics including age, sex, comorbidities, clinical findings, treatment details, and adverse events were recorded. A total of 17 eyes of 17 patients were included. Median age was 43 years old and 53% of patients were male. Mean treatment duration was 25.4 ± 15.5 months. Indications for RCI therapy were scleritis (7 anterior and 1 posterior) (47.8%), panuveitis (17.4%), retinal vasculitis (17.4%), chronic/recurrent anterior uveitis (13%), and posterior uveitis (4.35%). RCI was initiated at a dose of 40 to 80 units 3 times weekly. Given the adequate control of inflammation, RCI was successfully discontinued in four patients (23.5%). Prior to RCI therapy, 14 (82.3%) patients were on oral prednisone at an average of 10 mg daily (range 2.5-40 mg), and two (11.7%) patients discontinued prednisone immediately before initiating RCI due to side effects. After six months of therapy, the prednisone dose was reduced in four (23.5%) patients to an average of 3 mg daily (range 1-5 mg) and was stopped in eight (53%) patients. Concomitant immunomodulatory therapies (IMTs) included mycophenolate mofetil (23.5%) and methotrexate (23.5%), and adalimumab (23.5%). Ten patients were on IMTs prior to using RCI, and during the course of treatment, IMT was stopped in two patients and reduced in one. Side effects included insomnia (23%), hypertension (11.7%), lower extremity edema (11.7%), hyperglycemia (11.7%), weight gain (11.7%), and infection (5.8%). RCI may be considered as a potential therapy with acceptable tolerability for patients with non-infectious scleritis or uveitis.
antibodies
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.
2026-06-25 | Uveitis in spondyloarthritis: clinical patterns and differences between axial and peripheral forms.
The association between uveitis and spondyloarthritis is well established. However, its characterization across the different types of spondyloarthritis remains limited in the literature. Therefore, this study aimed to perform a comparative characterization of uveitis in the various types of spondyloarthritis. Retrospective observational study that included patients with non-infectious uveitis and spondyloarthritis from a multidisciplinary uveitis clinic. A descriptive analysis was performed across the different subtypes of spondyloarthritis, followed by a comparative analysis regrouping patients into axial and peripheral SpA categories. 163 patients with spondyloarthritis-associated uveitis were included, comprising radiographic axial spondyloarthritis (49%), non-radiographic axial spondyloarthritis (21%), spondyloarthritis associated with inflammatory bowel disease (13%), psoriatic arthritis (12%), and peripheral spondyloarthritis (4%). Anterior uveitis (97%), acute relapsing course (79%), and alternating laterality (47.4%) were predominant in the overall sample. When comparing axial versus peripheral forms, significant differences were observed: intermediate, posterior, and panuveitis locations occurred exclusively in the peripheral forms, which also showed higher frequencies of chronic courses (p < 0.001), bilateralism (p < 0.05), and greater use of systemic therapy (p = 0.05). Regarding this treatment to control uveitis, 28.2% of patients required immunomodulatory therapy (more sulfasalazine in axial forms, and methotrexate in peripheral) and 17.8% required biologic therapy. Biologic discontinuation was higher in peripheral forms (p = 0.059). Variables predicting greater need for systemic therapy included chronic course, bilateralism, higher number of annual episodes, younger age of onset, peripheral joint involvement, and presence of vitritis (all p < 0.05). Acute anterior uveitis constitutes the most frequent pattern in all spondyloarthritis types. However, peripheral forms exhibit a higher prevalence of non-anterior, chronic, and bilateral uveitis, and, additionally, appeared to require greater use of immunomodulatory therapy. Key Points • Understanding and distinguishing the ocular inflammatory processes associated with SpA may have important therapeutic and prognostic implications. • Although acute recurrent anterior uveitis was the most frequent patternacross all SpA subtypes, in the peripheral SpA group (pSpA, IBD-SpA, and PsA) a higher prevalence of intermediate, posterior, panuveitis, chronic course, and bilateral uveitis was observed. • The peripheral SpA group (pSpA, IBD-SpA, and PsA) appeared to require greater use of immunomodulatory drugs (csDMARDs or biologics) for control of the ocular condition, suggesting the need for closer monitoring and tailored therapeutic strategies.
2026-05-27 | Recent updates in human leukocyte antigen B27-associated uveitis.
There has been progressive understanding in etiopathogenesis, clinical presentation, and effective treatment of anterior uveitis (AU) over the years. Sudden onset, symptomatic acute anterior uveitis (AAU) in a young adult, often male, classically arouses suspicion for human leukocyte antigen (HLA) B27-related uveitis. While the ocular presentation is frequently the earliest manifestation, its systemic counterparts within the spectrum, viz., spondyloarthropathies (SpA), including ankylosing spondylitis (AS), reactive arthritis (RA), psoriatic arthritis (PA), and inflammatory bowel disease-associated inflammation, pose greater diagnostic and therapeutic challenges for rheumatologists and internists. This places the ophthalmologist in a uniquely advantageous yet responsible position in initiating etiologic evaluation and facilitating early systemic recognition. Rapid advances in immunology and molecular medicine have significantly expanded the diagnostic and therapeutic landscape of HLA B27-related disease. Emerging insights implicating the gut microbiome, autoinflammatory mechanisms, and innate immune dysregulation have reshaped traditional concepts of pathogenesis. Concurrently, an improved understanding of cytokine networks and immune signaling pathways has led to the development of targeted biologic and synthetic disease-modifying therapies. Given the dynamic, multisystem nature of HLA B27-associated disease and its variable organ involvement, optimal management necessitates close multidisciplinary collaboration among ophthalmologists, rheumatologists, gastroenterologists, and internists. This article briefly explores the evolving concepts of the complex enigma of the HLA B27 molecule and the basis for recent trends in its understanding at the cellular, molecular, biochemical, and clinical levels.
2026-05-23 | Acute tear-film disruption in treatment-naive acute anterior uveitis: A retrospective case-control study.
The study aimed to quantify the acute tear-film disruption in treatment-naive, 1st-onset noninfectious acute anterior uveitis (AAU) and identify independent and modifiable determinants. Retrospective case-control study enrolling 180 AAU eyes and 90 age-/sex-matched healthy controls. Same-day noninvasive tear breakup time (NIBUT), tear meniscus height, Schirmer-I and Ocular Surface Disease Index were extracted. Multivariable linear regression with bootstrap correction determined predictors of shorter NIBUT. Mean NIBUT was 4.7 seconds lower in AAU than controls (5.7 ± 1.5 seconds vs 10.4 ± 1.5 seconds; P < .001); 66% of AAU eyes versus 2% of controls had NIBUT ≤ 5 seconds. Tear meniscus height (-81 μm), Schirmer-I (-5.3 mm) and Ocular Surface Disease Index (+24 points) all worsened (P < .001). Independent reductions in NIBUT: anterior-chamber cells ≥ 2+ (-1.79 seconds), flare ≥ 3+ (-1.23 seconds), concomitant meibomian gland dysfunction (-0.96 seconds) and daily screen time > 8 hours (-0.59 seconds); adjusted R2 = 0.38, optimism-corrected R2 = 0.35. In this proof-of-concept study, 1st-onset AAU was associated with measurable tear-film destabilization driven by intraocular inflammatory load. While these findings suggest a potential role for early ocular-surface protection, effect sizes represent upper-bound estimates requiring confirmation in unscreened populations before routine clinical application.
2026-05-20 | Interface Between Ophthalmology and Rheumatology in Uveitis and Retinal Vasculitis in Adult Patients, When Does Who Need Whom?
BACKGROUND: There is a significant interface between ophthalmology and rheumatology, particularly in uveitis and retinal vasculitis. This will be described in detail here. RESULTS: Analyses of uveitis consultations from university centres in Austria and Germany show that approximately 30% of anterior uveitis cases, 17% of intermediate and posterior uveitis cases, 7% of panuveitis cases, and 20% of retinal vasculitis cases, are associated with an inflammatory rheumatic systemic disease. The most frequent association (30%) is between spondyloarthritis and psoriatic arthritis with anterior uveitis (AAU). In approximately 1.3% of cases of intermediate uveitis, sarcoidosis is present, while in posterior uveitis and panuveitis, Behcet's syndrome (BS) is the most likely cause (2.5% and 12.6%, respectively). Retinal vasculitis is associated with BS in 18% of cases. Easily detectable "red flags" for inflammatory rheumatic diseases and the influence of uveitis on systemic immunomodulatory therapy in rheumatology have been described. For example, in AAU during SPA, monoclonal tumour necrosis factor inhibitors (TNFi) are more effective than etanercept, a fusion protein of the TNF receptor and immunoglobulin Fc segment. IL-17 antagonists and Janus-Kinase (JAK) inhibitors are also able to reduce the risk of uveitis flares, but are less effective than monoclonal TNFi. SUMMARY: Close collaboration between rheumatologists and ophthalmologists is essential, particularly in the treatment of uveitis and retinal vasculitis. Assessment for certain warning signs and determination of specific laboratory parameters are helpful in detecting the association, present in approximately 20% of cases, between uveitis and retinal vasculitis and inflammatory rheumatic systemic diseases, and in referring patients specifically to rheumatology. Conversely, rheumatologists require precise ophthalmological findings and information on treatment response, in order to adjust therapy in a targeted manner or, in cases of ocular symptoms associated with an underlying inflammatory systemic disease, in order to appropriately adapt the therapy to the ocular involvement.
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
2026-02-23 | 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.
2005-12-13 | Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF‐α soluble receptor in uveitis
Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long-lasting expression and secretion of therapeutic proteins. High and long-lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF-alpha soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxin-induced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.
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Drug Discovery Landscape
2 orphan drug designations for Anterior uveitis.
2 orphan drug designations for Anterior uveitis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
E. Coli heat-shock protein 70 with bovine retinal S-antigen | proteins | EMA | 2006-01-24 | — | Biotech Tools SA |
AI-RSA | small molecules | FDA | 1992-10-08 | — | AutoImmune, Inc. |
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