RARE DISEASE
Idiopathic posterior uveitis
Idiopathic posterior uveitis
Idiopathic posterior uveitis
Drug discovery
1
drug
With orphan designation
Overview
Idiopathic posterior uveitis is a rare, vision-threatening inflammation of the choroid, retina, or optic nerve without identifiable infectious or systemic causes. It presents as focal, multifocal, or diffuse noninfectious inflammation, often leading to complications like cystoid macular edema and choroidal neovascularization. Diagnosis requires exclusion of infectious etiologies and systemic autoimmune conditions [6][11][14].
Burden
Annual direct medical costs average $12,149 per patient, exceeding anterior uveitis costs by 55% [4].
Up to 93% of patients report vision-related quality-of-life impairments, even with controlled inflammation [4][9].
Complications (e.g., retinal scarring, glaucoma) cause irreversible vision loss in 20% of cases [6][14][17].
Therapies
First-line: Local/systemic corticosteroids (e.g., intravitreal dexamethasone implants, oral prednisone) to suppress inflammation [1][8][13].
Immunomodulators: Methotrexate, mycophenolate, or biologics (adalimumab) for steroid-sparing management [3][13][18].
Sustained-release implants: Fluocinolone acetonide or dexamethasone for refractory cases [13][18].
Categories: rare ophthalmic disorders
Research Papers
204 drug discovery papers about Idiopathic posterior uveitis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
204 drug discovery papers about Idiopathic posterior uveitis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-01-25 | The protein-protein interaction network analysis in idiopathic posterior uveitis.
Idiopathic posterior uveitis (IPU) is a vision-threatening inflammatory condition affecting the posterior segment of the eye with poorly understood molecular mechanisms. This study aimed to identify the key molecular actors and functional pathways involved in IPU using protein-protein interaction (PPI) network analysis. In silico bioinformatics study using PPI network analysis to identify key molecular pathways in IPU. Sixteen proteins previously linked to IPU pathogenesis were identified in a comprehensive literature review. These seed proteins were used to query the STRING v12 database to retrieve high-confidence interactions (score ≥ 700). An expanded PPI network was built and analyzed using Python tools, including NetworkX and Louvain community detection algorithm. Topological metrics (degree, betweenness, and eigenvector centrality) were calculated to identify the hub and bottleneck proteins. Functional enrichment analysis was performed to assess the biological significance. The resulting PPI network consisted of 260 proteins and 281 interactions. The network exhibited a low density (0.008) but a high modularity (0.8426), which is consistent with typical biological networks. Key hub proteins included PDGFRB, ORM1, IL23A, and TIMP1. Proteins such as IL6, KITLG, and STAT4 emerged as critical bottlenecks based on betweenness centrality. Multimetric centrality analysis highlighted TIMP1, TIMP2, KITLG, and IL6 as potential master regulators. The findings highlight the inflammatory, structural, and neurotrophic pathways as key components of disease pathogenesis, suggesting novel molecular targets for future therapeutic investigations. PPI network analysis offers a robust framework for uncovering the disease mechanisms in complex ocular inflammatory conditions.
2024-04-25 | Adalimumab (ADA) in Pediatric Non-infectious Uveitis: An Observational Study
Objectives: Pediatric uveitis is a rare but sight-threatening condition. Prompt and adequate treatment is crucial to preserve vision and avoid long-term complications. In cases that are resistant to corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), anti-tumor necrosis (anti-TNF) biologic agents are usually added. In this study, we report our experience with adalimumab (ADA) anti-TNF use in this group of patients. Methods: This is a retrospective observational study conducted in a tertiary pediatric uveitis clinic, in Manchester Royal Eye Hospital. All patients were pediatric patients (aged 2-18 years old) under follow-up during the period of six months. The patients' data were analyzed according to the diagnosis, age of onset of uveitis, systemic medications used before and concomitantly with ADA, duration of uveitis before starting ADA, its effect, and time to notice the therapeutic effect in controlling inflammation. Finally, cases were reviewed for the development of anti-drug antibodies. Results: Forty-two patients were included in the study. Idiopathic uveitis was diagnosed in 47.6% of patients and 40.5% of patients were associated with juvenile idiopathic arthritis (JIA). Most (97.6%) of patients were using topical steroids before starting ADA and 95.2% continued using steroids after established ADA use, but systemic steroid use was reduced from 33.3% to 14.3%. The most common non-biologic DMARD used before ADA was methotrexate (MTX) (90.5%). One-third of the patients started ADA between 6 and 12 months after the diagnosis of uveitis, while this percentage dropped to 9.5% the year after diagnosis. Seventy-eight percent of patients acquired complete clinical control of inflammation on ADA use. Almost 78.6% of patients showed a full response in less than six months. In eight patients who were not controlled or were transiently controlled on ADA, three patients had positive anti-drug antibodies. In one patient, antidrug antibodies were identified after 12 years of ADA use, and in another, after 4 years. Conclusion: Adalimumab is an effective, well-tolerated drug in children with uveitis refractory to non-biologic DMARD therapy. DMARDs were usually used alongside ADA in this cohort and few patients had confirmed ADA antibodies.
2024-04-15 | AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?
Abstract Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.
2024-04-03 | Hyalocytes—guardians of the vitreoretinal interface
Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease. Hyalocytes are involved in fetal vitreous development, hyaloid vasculature regression, surveillance and metabolism of the vitreoretinal interface, synthesis and breakdown of vitreous components, and maintenance of vitreous transparency. While sharing certain resemblances with other myeloid cell populations such as retinal microglia, hyalocytes possess a distinct molecular signature and exhibit a gene expression profile tailored to the specific needs of their host tissue. In addition to inflammatory eye diseases such as uveitis, hyalocytes play important roles in conditions characterized by anomalous posterior vitreous detachment (PVD) and vitreoschisis. These can be hypercellular tractional vitreo-retinopathies, such as macular pucker, proliferative vitreo-retinopathy (PVR), and proliferative diabetic vitreo-retinopathy (PDVR), as well as paucicellular disorders such as vitreo-macular traction syndrome and macular holes. Notably, hyalocytes assume a significant role in the early pathophysiology of these disorders by promoting cell migration and proliferation, as well as subsequent membrane contraction, and vitreoretinal traction. Thus, early intervention targeting hyalocytes could potentially mitigate disease progression and prevent the development of proliferative vitreoretinal disorders altogether, by eliminating the involvement of vitreous and hyalocytes.
2024-03-26 | Vitamin D status in active and inactive noninfectious uveitis - data from a reference university hospital in Rio de Janeiro, Brazil
PURPOSE: This study aimed to investigate the correlation between serum vitamin D levels and disease activity in patients with noninfectious uveitis. METHODS: We conducted a prospective case-control study, assessing 51 patients with noninfectious uveitis, categorized into active (n=22) and inactive (n=29) groups, along with 51 healthy controls. Serum 25-hydroxy vitamin D [25(OH)D] levels were measured. The uveitis group also completed a questionnaire regarding sunlight exposure habits and vitamin D supplementation. RESULTS: Patients with inflammation-related uveitis exhibited low serum 25(OH)D levels in 68% of cases. The median 25(OH)D level in patients with active uveitis was 17.8 ng/mL (interquartile range [IQR], 15-21 ng/mL), significantly lower compared to the 31.7 ng/mL (IQR, 25-39 ng/mL) in patients with inactive uveitis (p<0.001) and the 27 ng/mL (IQR, 23-31 ng/mL) in the Control Group (p<0.001). Significantly, nearly all patients with uveitis taking vitamin D supplementation were in the Inactive Group (p<0.005). Moreover, reduced sunlight exposure was associated with active uveitis (p<0.003). Furthermore, patients with 25(OH)D levels below 20 ng/mL had ten times higher odds of developing active uveitis (p=0.001). CONCLUSIONS: This study revealed a prevalent 25(OH)D deficiency among patients with noninfectious uveitis and suggested a link between low 25(OH)D levels and disease activity. To prevent future episodes of intraocular inflammation, vitamin D supplementation and controlled sunlight exposure could be viable options.
2026-01-25 | The protein-protein interaction network analysis in idiopathic posterior uveitis.
Idiopathic posterior uveitis (IPU) is a vision-threatening inflammatory condition affecting the posterior segment of the eye with poorly understood molecular mechanisms. This study aimed to identify the key molecular actors and functional pathways involved in IPU using protein-protein interaction (PPI) network analysis. In silico bioinformatics study using PPI network analysis to identify key molecular pathways in IPU. Sixteen proteins previously linked to IPU pathogenesis were identified in a comprehensive literature review. These seed proteins were used to query the STRING v12 database to retrieve high-confidence interactions (score ≥ 700). An expanded PPI network was built and analyzed using Python tools, including NetworkX and Louvain community detection algorithm. Topological metrics (degree, betweenness, and eigenvector centrality) were calculated to identify the hub and bottleneck proteins. Functional enrichment analysis was performed to assess the biological significance. The resulting PPI network consisted of 260 proteins and 281 interactions. The network exhibited a low density (0.008) but a high modularity (0.8426), which is consistent with typical biological networks. Key hub proteins included PDGFRB, ORM1, IL23A, and TIMP1. Proteins such as IL6, KITLG, and STAT4 emerged as critical bottlenecks based on betweenness centrality. Multimetric centrality analysis highlighted TIMP1, TIMP2, KITLG, and IL6 as potential master regulators. The findings highlight the inflammatory, structural, and neurotrophic pathways as key components of disease pathogenesis, suggesting novel molecular targets for future therapeutic investigations. PPI network analysis offers a robust framework for uncovering the disease mechanisms in complex ocular inflammatory conditions.
2024-04-25 | Adalimumab (ADA) in Pediatric Non-infectious Uveitis: An Observational Study
Objectives: Pediatric uveitis is a rare but sight-threatening condition. Prompt and adequate treatment is crucial to preserve vision and avoid long-term complications. In cases that are resistant to corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), anti-tumor necrosis (anti-TNF) biologic agents are usually added. In this study, we report our experience with adalimumab (ADA) anti-TNF use in this group of patients. Methods: This is a retrospective observational study conducted in a tertiary pediatric uveitis clinic, in Manchester Royal Eye Hospital. All patients were pediatric patients (aged 2-18 years old) under follow-up during the period of six months. The patients' data were analyzed according to the diagnosis, age of onset of uveitis, systemic medications used before and concomitantly with ADA, duration of uveitis before starting ADA, its effect, and time to notice the therapeutic effect in controlling inflammation. Finally, cases were reviewed for the development of anti-drug antibodies. Results: Forty-two patients were included in the study. Idiopathic uveitis was diagnosed in 47.6% of patients and 40.5% of patients were associated with juvenile idiopathic arthritis (JIA). Most (97.6%) of patients were using topical steroids before starting ADA and 95.2% continued using steroids after established ADA use, but systemic steroid use was reduced from 33.3% to 14.3%. The most common non-biologic DMARD used before ADA was methotrexate (MTX) (90.5%). One-third of the patients started ADA between 6 and 12 months after the diagnosis of uveitis, while this percentage dropped to 9.5% the year after diagnosis. Seventy-eight percent of patients acquired complete clinical control of inflammation on ADA use. Almost 78.6% of patients showed a full response in less than six months. In eight patients who were not controlled or were transiently controlled on ADA, three patients had positive anti-drug antibodies. In one patient, antidrug antibodies were identified after 12 years of ADA use, and in another, after 4 years. Conclusion: Adalimumab is an effective, well-tolerated drug in children with uveitis refractory to non-biologic DMARD therapy. DMARDs were usually used alongside ADA in this cohort and few patients had confirmed ADA antibodies.
2024-04-15 | AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?
Abstract Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.
2024-04-03 | Hyalocytes—guardians of the vitreoretinal interface
Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease. Hyalocytes are involved in fetal vitreous development, hyaloid vasculature regression, surveillance and metabolism of the vitreoretinal interface, synthesis and breakdown of vitreous components, and maintenance of vitreous transparency. While sharing certain resemblances with other myeloid cell populations such as retinal microglia, hyalocytes possess a distinct molecular signature and exhibit a gene expression profile tailored to the specific needs of their host tissue. In addition to inflammatory eye diseases such as uveitis, hyalocytes play important roles in conditions characterized by anomalous posterior vitreous detachment (PVD) and vitreoschisis. These can be hypercellular tractional vitreo-retinopathies, such as macular pucker, proliferative vitreo-retinopathy (PVR), and proliferative diabetic vitreo-retinopathy (PDVR), as well as paucicellular disorders such as vitreo-macular traction syndrome and macular holes. Notably, hyalocytes assume a significant role in the early pathophysiology of these disorders by promoting cell migration and proliferation, as well as subsequent membrane contraction, and vitreoretinal traction. Thus, early intervention targeting hyalocytes could potentially mitigate disease progression and prevent the development of proliferative vitreoretinal disorders altogether, by eliminating the involvement of vitreous and hyalocytes.
2024-03-26 | Vitamin D status in active and inactive noninfectious uveitis - data from a reference university hospital in Rio de Janeiro, Brazil
PURPOSE: This study aimed to investigate the correlation between serum vitamin D levels and disease activity in patients with noninfectious uveitis. METHODS: We conducted a prospective case-control study, assessing 51 patients with noninfectious uveitis, categorized into active (n=22) and inactive (n=29) groups, along with 51 healthy controls. Serum 25-hydroxy vitamin D [25(OH)D] levels were measured. The uveitis group also completed a questionnaire regarding sunlight exposure habits and vitamin D supplementation. RESULTS: Patients with inflammation-related uveitis exhibited low serum 25(OH)D levels in 68% of cases. The median 25(OH)D level in patients with active uveitis was 17.8 ng/mL (interquartile range [IQR], 15-21 ng/mL), significantly lower compared to the 31.7 ng/mL (IQR, 25-39 ng/mL) in patients with inactive uveitis (p<0.001) and the 27 ng/mL (IQR, 23-31 ng/mL) in the Control Group (p<0.001). Significantly, nearly all patients with uveitis taking vitamin D supplementation were in the Inactive Group (p<0.005). Moreover, reduced sunlight exposure was associated with active uveitis (p<0.003). Furthermore, patients with 25(OH)D levels below 20 ng/mL had ten times higher odds of developing active uveitis (p=0.001). CONCLUSIONS: This study revealed a prevalent 25(OH)D deficiency among patients with noninfectious uveitis and suggested a link between low 25(OH)D levels and disease activity. To prevent future episodes of intraocular inflammation, vitamin D supplementation and controlled sunlight exposure could be viable options.
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Drug Discovery Landscape
1 orphan drug designation for Idiopathic posterior uveitis, including 1 approved therapy.
1 orphan drug designation for Idiopathic posterior uveitis, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Fluocinolone [Retisert] | small molecules | FDA | 2000-07-31 | 2005-04-08 | Bausch & Lomb Pharmaceuticals, Inc. |
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