Uveitis Research Articles

Intravitreal application of stem cells and their products does not ameliorate experimental autoimmune uveitis

Aims/Purpose: Stem cell therapy has demonstrated potential therapeutic benefits in various medical disciplines. This study evaluated therapeutic effects of mesenchymal stem cells (MSCs) or their by‐products on intraocular inflammation in experimental autoimmune uveitis (EAU) model.Methods: EAU was induced in C57BL/6J mouse strain through administration of IRBP, Freund's adjuvant and pertussis toxin. Conditioned medium was procured through cultivation of MSCs in serum‐free medium, while MSC supernatant was obtained via MSC centrifugation and membrane removal. Either conditioned medium or MSC supernatant was intravitreally administered unilaterally, typically on day 14 post‐EAU induction. Ocular fundus of mice was documented regularly. Experiments were generally concluded on day 28, with eyes processed for FACS and PCR analysis. Infiltration of retina by inflammatory cells (F4/80, CD11c, CD45, CD80, CD86, CD206) and gene expression of pro‐inflammatory factors (Gfap, Iba‐1, IL‐1, iNOS) were quantified.Results: Across all experiments, clinical grading, FACS, and PCR analysis indicated exacerbation of intraocular inflammation. Post‐intravitreal administration of MSC by‐products into eyes with EAU, increased infiltration of retina by inflammatory cells and upregulation in gene expression of pro‐inflammatory factors were observed. These findings were corroborated in vitro, where co‐culturing of retina with EAU in presence of MSCs or their supernatant did not significantly reduce gene expression of pro‐inflammatory factors. Upsurge in pro‐inflammatory factors was also noted in control experiments on healthy eyes post‐intravitreal injection of no substance, serum‐free medium, PBS, or conditioned medium.Conclusions: No improvement in EAU was observed following application of MSC products, both in vivo and in vitro. Instead, inflammation was more severe. Trauma induced by intravitreal application itself significantly influenced outcome.Financial support: GA UK 309621, SVV UK 260631.

PIM1 signaling in immunoinflammatory diseases: an emerging therapeutic target.

PIM1, the proviral integration site for Moloney murine leukemia virus, is a member of the serine/threonine protein kinase family. It is involved in many biological events, such as cell survival, cell cycle progression, cell proliferation, and cell migration, and has been widely studied in malignant diseases. However, recent studies have shown that PIM1 plays a prominent role in immunoinflammatory diseases, including autoimmune uveitis, inflammatory bowel disease, asthma, and rheumatoid arthritis. PIM1 can function in inflammatory signal transduction by phosphorylating multiple inflammatory protein substrates and mediating macrophage activation and T lymphocyte cell specification, thus participating in the development of multiple immunoinflammatory diseases. Moreover, the inhibition of PIM1 has been demonstrated to ameliorate certain immunoinflammatory disorders. Based on these studies, we suggest PIM1 as a potential therapeutic target for immunoinflammatory diseases and a valid candidate for future research. Herein, for the first time, we provide a detailed review that focuses on the roles of PIM1 in the pathogenesis of immunoinflammatory diseases.

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood

Changes in Central Corneal Thickness, Corrected Intraocular Pressure, and Iridocorneal Angle in Unilateral Acute Anterior Uveitis.

The release of inflammatory mediators in the anterior chamber can lead to the structural alteration of the corneal and uveal tissue. To compare the changes in Central Corneal Thickness (CCT), corrected Intraocular Pressure (cIOP) and Iridocorneal Angle (ICA) in unilateral acute anterior uveitis (AAU) before and after treatment. The study was a hospital based comparative study conducted between July 2018 to June 2019. Newly diagnosed, untreated unilateral Acute Anterior Uveitis (AAU) adult cases above 16 years were included in the study. Ethical clearance was obtained from the Institutional Review Committee of Institute of Medicine. Eighty-two unilateral AAU cases (Total 164 eyes including 82 unaffected were analyzed) underwent Goldmann applanation tonometry (GAT) and corneal topography at presentation and three weeks after treatment. The cIOP was calculated by the Ehlers formula. The mean CCT of affected eyes was greater (563.84±51.49μm) compared to unaffected eyes (535.99±31.48μm) before treatment (p=0.001) and was reduced (533.2±25.71μm) after treatment (p=0.01). There was no significant difference in IOP, cIOP, and ICA between the affected eyes (14.45±6.89mmHg, 13.14±7.14mmHg and 48.78±7.94°) and the unaffected eyes (14.02±2.36mmHg, 14.4±3.09mmHg, and 49.80°±8.21°) before treatment. There was no difference in IOP (14.04±2.76mmHg) and ICA (49.21°±6.72°) after treatment, however, there was a significant increase (p=0.01) in the cIOP (14.95±2.93mmHg). In the study, CCT of affected eyes was greater compared to unaffected eyes and reduced after treatment. There was no difference in cIOP and ICA in case eyes compared to control before treatment. However, cIOP increased after treatment.

Single-cell sequencing of the retina shows that LDHA regulates pathogenesis of autoimmune uveitis

Autoimmune uveitis (AU) is a severe disorder causing poor vision and blindness. However, the cellular dynamics and pathogenic mechanisms underlying retinal injury in uveitis remain unclear. In this study, single-cell RNA sequencing of the retina and cervical draining lymph nodes in experimental autoimmune uveitis mice was conducted to identify the cellular spatiotemporal dynamics and upregulation of the glycolysis-related gene LDHA. Suppression of LDHA can rescue the imbalance of T effector (Teff) cells/T regulator (Treg) cells under inflammation via downregulation of the glycolysis-PI3K signaling circuit and inhibition of the migration of CXCR4+ Teff cells towards retinal tissue. Furthermore, LDHA and CXCR4 are upregulated in the peripheral blood mononuclear cells of Vogt-Koyanagi-Harada patients. The LDHA inhibitor suppresses CD4+ T cell proliferation in humans. Therefore, our data indicate that the autoimmune environment of uveitis regulates Teff cell accumulation in the retina via glycolysis-associated LDHA. Modulation of this target may provide a novel therapeutic strategy for treating AU.

Clinical manifestation and long-term follow-up of presumed ocular tuberculosis in China

BackgroundThis study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population. MethodsClinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed. ResultsThe study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%). ConclusionsOTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

Ten-year clinical outcome of recent-onset axial spondyloarthritis: Results from the DESIR inception Cohort

ObjectivesThis study aimed to evaluate the 10-year clinical outcome of patients with recent-onset axial spondyloarthritis (axSpA). Methods study designThe DESIR cohort is an inception cohort of axSpA patients. Methods diagnosis and managementThe diagnosis and management of patients were based on the decision of the treating rheumatologist. Methods statistical analysisBoth complete cases and imputed data analyses were conducted. ResultsOf the 708 enrolled patients, 45 were excluded due to a change in the baseline diagnosis, 3 patients died, and 300 were lost to follow-up over the 10years. In the completer population, one patient required bilateral total hip replacement, and 56 patients received a pension due to invalidity. The prevalence of main extra-musculoskeletal features increased from baseline to year 10: psoriasis from 18% to 30%, acute anterior uveitis from 10% to 18%, and inflammatory bowel disease from 5% to 10%. The most frequent comorbidity was hypertension, with an increase from 5% to 15% from baseline to year 10. In the imputed data analysis the estimated proportions of patients with an acceptable status at year 10 were 70% [95% CI: 63; 77] for acceptable PASS, 43% [95% CI: 37; 49] for BASDAI<3, and 48% [95% CI: 41; 56] for ASDAS<2.1. ConclusionThese findings suggest that despite a quite favorable 10-year outcome exists for severe outcomes, a large proportion of patients present with an important disease burden reflected by patient-reported outcomes. This information can be valuable for providing patients with information at the time of diagnosis.

Zapalenie przedniego odcinka błony naczyniowej spowodowane infekcją cytomegalowirusem u immunokompetentnych pacjentów – diagnostyka i leczenie na przykładzie przypadków klinicznych

Uveitis caused by reactivation of cytomegalovirus appears to be a rare disease that usually affects immunocompromised patients, but a recent review of the literature provides us with more and more examples of its occurrence in immunocompetent individuals as well. With the widespread use of polymerization chain reaction tests from the aqueous fluid, it has been demonstrated that cytomegalovirus may be responsible for most cases of the infectious iritis. The variable clinical course of cytomegalovirus anterior uveitis can make it difficult to provide an appropriate diagnosis. The key is to promptly initiate appropriate treatment and effectively prevent recurrence, as the reis a very high risk of complications, i.e. glaucoma or macular edema. Based on exemplary clinical cases, the different forms of inflammation, diagnosis and treatment are discussed.

The cytologic analysis of aqueous humor in eyes with uveitis

Purpose: The purpose of this study was to evaluate the cytologic analysis of aqueous humor (AH) of the eyes with Fuchs uveitis (FU) and idiopathic anterior uveitis (IAU). Methods: AH of 25 uveitic eyes (12 FU and 13 IAU) were evaluated cytologically. The samples of the anterior chamber were taken before cataract surgery. Aqueous fluid samples were evaluated by applying a Giemsa stain. Results: The 12 patients with FU and 13 patients with IAU were included in this study. In AH, the number of lymphocytes was similar in eyes with FU and IAU (the number of lymphocytes: min:1 and max:7). The acellular amorphous structures were detected in eyes with FU, and the same finding was not observed in the eyes with IAU. In addition, any pigmented cells or accumulation were not detected in any of the eyes. Conclusion: The acellular amorphous structures were the remarkable finding of this study. It has been considered that amorphous structures in the AH of the eyes with FU could be related to chronic, low-grade anterior chamber inflammation and responsible for several complications of uveitis. FU is a uveitic entity with mysterious findings that await clarifications in its etiopathogenesis.

Demographic and Clinical Characteristics of Uveitis for Adult Patients Attending Mansoura Ophthalmic Center

ABSTRACT Aim The aim of this research is to evaluate the demographic attributes and clinical manifestations of uveitis in adult patients frequenting the Mansoura Ophthalmic Center. Methods Utilizing a cross-sectional, prospective, analytical study design, this research engaged adult patients visiting the outpatient uveitis clinic at the Mansoura Ophthalmic Center. Comprehensive case evaluations involved collecting detailed patient histories, examining ophthalmic records, and conducting thorough ocular examinations. These examinations encompassed the assessment of visual acuity, slit-lamp examination, and fundus examination. Furthermore, selected cases underwent optical coherence tomography (OCT) and fundus fluorescein angiography (FFA). Results The Study involved an examination of 411 eyes belonging to 254 uveitic patients. In the Egyptian context, anterior uveitis surfaced as the most prevalent form of uveitis. The average Best-Corrected Visual Acuity (BCVA) among the cases studied was 0.797 ± 0.77 LogMAR, with the majority of cases demonstrating vision superior to 0.3 LogMAR. Notably, the principal causes of vision loss were generally reversible. Macular edema was identified as the leading cause of vision loss, representing 20.7% of cases as evidenced by OCT. The ratio of non-infectious to infectious uveitis stood at 92.2% to 7.8%. The most commonly observed etiologies of non-infectious uveitis included Behçet’s disease (33.3%), Vogt-Koyanagi-Harada (VKH) syndrome (19.7%), idiopathic causes (19.2%), and ankylosing spondylitis (AS) (11.9%). Conversely, the most frequent infectious etiologies were trematode-induced uveitis (2.9%), herpetic uveitis (1.7%), toxoplasmosis (1.5%), tuberculosis (TB) (1.5%), and brucellosis (0.2%). Conclusions This study conclusively indicates that anterior uveitis is the predominant anatomical type of uveitis in Egypt. Further, etiological diagnoses of uveitis should particularly emphasize Behçet’s disease, VKH syndrome, and ankylosing spondylitis.

Crohn's disease and clinical management today: How it does?

Crohn's Disease (CD) is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature. Its etiology results from the interaction between genetic, enviromental and microbial factors. Regarding pathophysiology, it involves high levels of interleukin (IL)-12, IL-17, and Th1 profile, along with loss of tolerance mechanisms, an increase in pro-inflammatory interleukins, beyond the possibility to affect any part of the gastrointestinal tract. Its symptoms include abdominal pain, chronic diarrhea, weight loss, anorexia, and fatigue, as well as blood in the stool or rectum. Additionally, conditions comprising musculoskeletal, cutaneous, ocular, hepatic, and hematological alterations may be associated with this scenario and extra-intestinal presentation, such as erythema nodosum, anterior uveitis, osteoporosis, and arthritis can also occur. Today, clinical history, exams as fecal calprotectin, ileocolonocopy, and capsule endoscopy can be performed in the diagnosis investigation, along with treatments to induce and maintain remission. In this sense, anti-inflammatory drugs, such as corticosteroids, immunomodulators, and biological agents, as well as surgery and non-pharmacological interventions plays a role in its therapy. The aim of this review is to bring more current evidence to clinical management of CD, as well as to briefly discuss aspects of its pathophysiology, surveillance, and associated disorders.

Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis.

The perception of circulating granulocytes as cells with a predetermined immune response mainly triggered by pathogens is evolving, recognizing their functional heterogeneity and adaptability, particularly within the neutrophil subset. The involvement of these cells in the pathophysiology of autoimmune uveitis has become increasingly clear, yet their exact role remains elusive. We used an equine model for autoimmune-mediated recurrent pan-uveitis to investigate early responses of granulocytes in different inflammatory environments. For this purpose, we performed differential proteomics on granulocytes from healthy and diseased horses stimulated with IL8, LPS, or PMA. Compared to healthy horses, granulocytes from the recurrent uveitis model significantly changed the cellular abundance of 384 proteins, with a considerable number of specific changes for each stimulant. To gain more insight into the functional impact of these stimulant-specific proteome changes in ERU pathogenesis, we used Ingenuity Pathway Analysis for pathway enrichment. This resulted in specific reaction patterns for each stimulant, with IL8 predominantly promoting Class I MHC-mediated antigen processing and presentation, LPS enhancing processes in phospholipid biosynthesis, and PMA, clearly inducing neutrophil degranulation. These findings shed light on the remarkably differentiated responses of neutrophils, offering valuable insights into their functional heterogeneity in a T-cell-driven disease. Raw data are available via ProteomeXchange with identifier PXD013648.

Epiretinal membrane in uveitis: Rate, visual prognosis, complications and surgical outcomes.

Epiretinal membrane (ERM) is a common finding in patients with uveitis that contributes to visual impairment. We describe the long-term visual acuity (VA) and morphometric progression in patients with uveitis and epiretinal membrane (ERM). Retrospective cohort study of patients with uveitic ERM from a tertiary centre database. Multivariate analysis of risk factors for ERM progression was calculated using a marginal Cox regression model to estimate hazard ratios (HR). Two hundred and sixteen eyes (4%) of a total 5450 eyes with uveitis were identified to have an ERM. The most common diagnosis was idiopathic uveitis in 45 patients (28.7%), followed by sarcoidosis in 21 (13.4%), HLAB27-related uveitis in 15 (9.6%) and toxoplasmosis in 15 (9.6%). Risk factors for ERM development include age (HR 1.03), intermediate uveitis (HR 2.33), posterior uveitis (HR 1.53) and ERM fellow eye (HR 18.28). Anterior uveitis (HR 0.53) and alternating disease (HR 0.53) were protective. Median VA was 20/40 at diagnosis of ERM and 20/40 at final follow up. Progression of ERM grade occurred in 17 eyes (7.9%) during the study period. ERM peel was performed in 44 eyes (20.4%). Median VA was 20/60 and 20/40 at baseline and 12 months after surgery, respectively. Improvement in visual acuity occurred in 23 eyes (60.5%) following surgery. In addition to intermediate and posterior uveitis, fellow eye involvement is a strong risk factor for ERM development. In treated uveitis, the majority maintain their long-term vision and rates of ERM progression are low.

Tuberculosis reactivation demonstrated by choroiditis and inflammatory choroidal neovascular membrane in a patient treated with immune checkpoint inhibitors for malignant mucosal melanoma

PurposeTo describe a complex case of ocular tuberculosis reactivation with anterior uveitis, choroiditis and inflammatory choroidal neovascular membrane (CNVM) following immune checkpoint inhibitor (ICPI) treatment of malignant mucosal melanoma.MethodsA retrospective collection of medical history, clinical findings and multimodal imaging with literature review of the topic was conducted.ResultsA 52-year-old Romanian female developed reduced vision and photophobia after three cycles of ICPI therapy comprised of ipilimumab and nivolumab. Bilateral anterior uveitis, multiple left eye choroidal lesions and a CNVM were confirmed using slit-lamp examination with ancillary multimodal imaging. Retinal changes in the right eye as well as a history of previously treated posterior uveitis and high-risk ethnicity increased clinical suspicion for ocular tuberculosis (TB) reactivation. The diagnosis was confirmed by TB positivity on polymerase chain reaction (PCR) analysis of lung aspirate followed by significant clinical improvement on systemic anti-tubercular therapy (ATT), systemic steroids and anti-vascular endothelial growth factor (VEGF) therapy.ConclusionsICPIs can cause a myriad of ocular issues, both by primary immunomodulatory effects as well as secondary reactivation of latent disease.

Leptospiral Uveitis: Case Series and Review of Literature

ABSTRACT Aim To present the clinical features and review of literature of leptospiral uveitis. Methods We present clinical features of patients with leptospiral uveitis with positive Leptospira IgM antibodies. Results Twenty-six eyes of 24 patients, 11 males (45.8%), were included. The mean age was 37.5 ± 15.6 years. 91.7% had unilateral uveitis, 88.5% panuveitis, 11.5% anterior uveitis, 15.4% had hypopyon, 8% had cataract and 3.8% eyes had cystoid macular edema. Vitritis with characteristic vitreous membranes was an important feature. Retinal and choroidal vasculature were preserved on swept-source optical coherence tomography angiography. Mean presenting BCVA was logMAR0.49 ± 0.41, while final BCVA was logMAR0.04 ± 0.13. The mean duration for complete resolution of uveitis was 39.1 ± 15.5 days. 84.6% eyes achieved BCVA 6/6. Conclusion Leptospiral uveitis is an under-reported entity. It may present as anterior uveitis or panuveitis. It must be included in the differential diagnosis of non-granulomatous uveitis. The visual prognosis is usually favorable even in severe cases.

Тубулоинтерстициальный нефрит с увеитом: серия клинических наблюдений

Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare autoimmune disease that develops predominantly in young people and is characterized by variable clinical manifestations and an uncertain prognosis. A single-center retrospective observational study included 3 pediatric patients (a girl and two boys) with clinically and morphologically confirmed TINU. Age of onset, clinical symptoms, gender-age-height-standardized blood pressure (BP), proteinuria (g/l), excretion level of β2-microglobulin, glucose, phosphorus in urine, blood pH and bicarbonate levels, Bedside Schwartz equation estimated glomerular filtration rate (eGFR, ml/min/1.73 m2, norm≥90 ml/min/1.73 m2), ophthalmoscopy data and the therapy were analyzed at the time of disease manifestation and during the follow-up. The duration of follow-up ranged from 3 to 7 years. The disease debuted at the age of 10 to 14 y/o with severe symptoms of intoxication, inflammatory activity, acute kidney damage (eGFR=22 to 35 ml/min/1.73 m2) and the development of Fanconi syndrome. Anterior uveitis had manifested in 1 to 5 months after the kidney disease. The TINU diagnosis was established after 6 to 9 months from the onset of the disease. All children received systemic steroid therapy coupled with the local treatment for uveitis. A significant decrease in blood creatinine levels and urine β2-microglobulin excretion with partial restoration of renal filtration function was noted by the sixth month of the therapy. All children developed chronic kidney disease (CKD) stages 2 to 3 over time. Stable remission of uveitis was achieved in 2 children after 3 to 10 months of treatment without complications; and in one patient a subacute uveitis led to the secondary changes in the cornea and decreased visual acuity. Conclusion: children with TINU have a high risk of developing CKD as a result of acute kidney disease; uveitis is characterized by a chronic course and, in the absence of remission, can lead to the development of ophthalmological complications.

Ocular Manifestations of Flavivirus Infections.

Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.

Effects of Goji Berries Extract on Acute Anterior Uveitis in Rats

Effects of Goji Berries Extract on Acute Anterior Uveitis in Rats

Retinal Vasculitis Following COVID-19 Infection: A Systematic Review

PURPOSE: We conducted a systematic review of literature to identify cases of vasculitis following corona-virus disease (COVID-19) infection and analyse their specific systemic and ocular features. METHODS: We used the key-words “retina” AND “vasculitis” AND vessels” AND COVID-19 to identify potential papers. We analysed case series, and case reports. RESULTS: 10 papers that describing 12 patients contained enough data to permit analysis and these were included in the study. There were seven female (58.3%) and five male patients (41.6%) with ages ranging from 11 to 66 (mean 42.6 years). Time from onset of the vasculitis following COVID-19 infection varied from three to 150 days (mean 41.0 days). Clinical findings were described in 15 of the 24 eyes of these 12 patients (62.5%) and included anterior uveitis; optic neuropathies; retinal infiltrates and clinical and unilateral or bilateral retinal vasculitis. CONCLUSIONS: Patients with retinal vasculitis appear to constitute a distinct subset and may require different treatment protocols.

Exploring the involvement of the alternative complement pathway in non-infectious uveitis pathogenesis.

Non-infectious uveitis is a complex disease characterized by intraocular inflammation of the uveal area and the leading cause of vision impairment and blindness in young people globally. However, what triggers inflammation and contributes to its recurrence remains unclear. The complement system has been linked to various immunological and inflammatory conditions. In the present study, we have systematically evaluated the role of the alternative complement pathway in the pathogenesis of non-infectious uveitis. Quantitative PCR was done in the peripheral leukocytes to study the expression of genes and regulatory miRNA in both anterior and posterior uveitis (n=28 in each category). Multiplex ELISA was performed to measure alternative pathway complement components, such as C3b, factor B, and CFH, and aqueous humor of infectious and non-infectious uveitis patients and non-inflammatory controls (n=10 each). Western blotting was done to validate the ELISA findings in a subset of patients and controls. Downregulation of C3 and CFH mRNA in the peripheral blood was shown by quantitative PCR in the group of anterior uveiits (AU), while the opposite result was found in the group of posterior uveitis (PU). ELISA levels of C3b and CFH proteins were significantly higher in aqueous humor of infectious and non-infectious uveitis (*p = 0.03 and **p = 0.0007 respectively) as compared to the control group. Western blotting further validated (VitH) the activation of the complement cascade in the aqueous (AH) and vitreous humor of patients with non-infectious uveitis, with an increased level of C3b (n=6) and CFH (n=4) in aqueous humor. C3b level was significantly increased while CFH was reduced relative to controls in the vitreous humor (VitH) of posterior uveitis patients compared to controls (n=27 in each category). A C3b to CFH ratio was computed to assess the regulation of complement activation and this index was several folds higher in both anterior and posterior uveitis (n=10 each). The expression of miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH was downregulated and nicely correlated with the increased complement proteins in both anterior and posterior uveitis (n=10 each). Our results demonstrate a clear role of CFH and the activation of the alternative complement pathway in the pathogenesis of non-infectious uveitis; however, its therapeutic potential warrants further investigations.