Autoimmune Liver Disease Associated Uveitis: An Extrahepatic Manifestation or a Polyautoimmunity Phenomenon? Case Reports.

PURPOSE: To report two cases of non-granulomatous unilateral anterior uveitis in two female patients associated with autoimmune liver diseases (ALD), emphasizing the possibility of this rare coexistence as a polyautoimmunity phenomenon. CASE DESCRIPTIONS: Case 1: An 18-year-old female with a history of congenital renal hypoplasia and metabolic syndrome presented with anterior uveitis in OS and a history of jaundice, blood elevated hepatic enzymes, and cholangioresonance compatible with primary sclerosing cholangitis (PSC). Laboratory work-up for additional autoimmune and infective causes were within normal limits. Case 2: An 58-year-old female presented an episode of anterior uveitis in OD and a history of Sjögren syndrome diagnosed at the age of 53, primary biliary cholangitis (PBC), systemic sclerosis, Raynaud's phenomenon, bilateral sacroiliitis, and vitiligo, consistent with polyautoimmunity and multiple autoimmune syndrome. CONCLUSIONS: Uveitis rarely coexists with ALD. However, it is essential to recognize the possibility of polyautoimmunity in patients presenting with ophthalmic manifestations and a previous diagnosis of ALD, such as PSC or PBC.

Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA).

PURPOSE: To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. METHODS: Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitis from January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. RESULTS: The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. CONCLUSION: This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patterns of uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation.

Mesenchymal Stromal Cells from Human Wharton's Jelly Modulate the Intraocular Immune Response in a Glucocorticoid Hypertension Model: An Exploratory Analysis.

INTRODUCTION: Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells. Recent research suggests immunological changes such as cytokine imbalance may affect its pathophysiology. This implies that immunomodulation, like that of mesenchymal cells, could be a potential therapeutic avenue for this disease. However, the effects of intravitreal injections of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) on intraocular immune response have not been assessed in ocular hypertension (OH) models. METHODS: We explored this by measuring cytokine levels and expression of other markers, such as glial fibrillary acidic protein (GFAP) and T cells, in 15 randomly divided New Zealand rabbits: G1: OH, G2: hWJ-MSCs, and G3: OH+hWJ-MSCs. We analyzed the aqueous humor (IL-6, IL-8, and TNF-α) and vitreous humor (IFN-γ, IL-10, and TGF-ß) using ELISA and flow cytometry (cell populations), as well as TCD3+, TCD3+/TCD4+, and TCD3+/TCD8+ lymphocytes, and GFAP in the retina and optic nerve through immunohistochemistry. RESULTS: We found a decrease in TNF-α, IL-6, IFN-γ, IL-10, and IL-8 in G3 compared to G1 and an increase in TGF-ß in both G2 and G3. TCD3+ retinal infiltration in all groups was primarily TCD8+ rather than TCD4+ cells, and strong GFAP expression was observed in both the retina and optic nerves in all groups. CONCLUSION: Our results suggest that cellular and humoral immune responses may play a role in glaucomatous optic neuropathy and that intravitreal hWJ-MSCs can induce an immunosuppressive environment by inhibiting proinflammatory cytokines and enhancing regulatory cytokines.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.

Prevalence and clinical characteristics of uveitic glaucoma: multicentric study in Bogotá, Colombia.

OBJECTIVES: To describe the clinical features of patients diagnosed with uveitic glaucoma (UG) and ocular hypertension secondary to uveitis (OHT-SU). METHODS: A multicentric cross-sectional study using medical records of patients with uveitis between 2013 and 2021. Uveitis and glaucoma specialists examined all patients. Variables were analyzed using the chi-square or Fisher's exact test for categorical variables. Additionally, t test, Mann-Whitney, and Kruskal-Wallis variance analysis were used for continuous variables. Finally, a Kaplan-Meier survival analysis for UG and OHT-SU development over time was done. RESULTS: Of the 660 clinical records reviewed of patients with uveitis, 191 (28.9%) had OHT-SU in at least one visit, and 108 (16.4%) of them developed UG. In all ages, females were more affected than males. Anterior uveitis was the main anatomic localisation, and non-granulomatous, recurrent, and inactive uveitis were the most frequent clinical features. The mean final visual acuity was 0.3 (0.0-1.0) LogMAR. Also, 95.8% of the patients had additional sequelae related to uveitis regardless of UG and OHT-SU. Interestingly, males had earlier affection, with statistical significance in OHT for adults (P = 0.036) and UG for children (P = 0.04). Of all patients, 81.1% received topical hypotensive treatment and 29.8% required a surgical procedure. CONCLUSIONS: UG and OHT-SU are common complications of uveitis in the Colombian population. These sight-threatening conditions were more common and appeared sooner in men at any age. Our results suggest that earlier and more aggressive treatment with topical hypotensive agents could positively influence the visual outcomes and the requirement of surgical procedures.

Risk factors for recurrences and visual impairment in patients with ocular toxoplasmosis: A systematic review and meta-analysis.

BACKGROUND: Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide. METHODS AND FINDINGS: We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836). RESULTS: Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%-58%), being more frequent in the South American population than in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%-48%) and blindness in 20% (95% CI 13%-30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72-8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59-6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment. CONCLUSION: Our Systematic Review showed that clinical factors such as being older than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy.

Sclerouveitis as Part of Multiple Autoimmune Syndrome in a Patient with Alkaptonuria: A Case Report.

PURPOSE: To present a novel association of multiple autoimmune syndrome (MAS) in a patient with sclerouveitis and alkaptonuria. CASE REPORT: A 68-year-old female with alkaptonuria, Hashimoto's thyroiditis, and familial autoimmunity presented with decreased VA, red eye, foreign body sensation, and ocular pain. Ophthalmological examination: OD conjunctival hyperemia, ochronosis, a reddish-violet scleral nodule, keratic precipitates, 2+ cells in the anterior chamber, 0.5+ vitreous cells, and mild vitreous haze. The patient was diagnosed with anterior uveitis and anterior nodular scleritis. Due to the associated sicca symptoms, a salivary gland biopsy was ordered, confirming Sjögren's syndrome. Then, MAS was diagnosed, and immunomodulatory medications were started; however, as she was refractory to more than two of them, it was suggested to start biological treatment. CONCLUSION: We present a novel MAS-type 2 pattern consisting of Hashimoto's thyroiditis, sclerouveitis, and Sjögren's syndrome. Its diagnosis and management represent a challenge, so a multidisciplinary approach should be provided.

A new look into uveitis in Colombia: changes in distribution patterns and clinical characteristics over the last 25 years.

PURPOSE: To describe the distribution patterns and clinical characteristics of patients diagnosed with uveitis at a specialized uveitis center in Bogotá, Colombia, from 2013 to 2021 and compare these patterns with the previously reported between 1996 and 2006. METHODS: We performed an observational descriptive cross-sectional study systematically reviewing clinical records of patients attending between 2013 and 2021. Data were analyzed and compared with previous reports. RESULTS: Of the 489 patients with uveitis, 310 were females (63.4%). The mean age of onset was 38.7, with a range between 1 and 83 years. Bilateral (52.8%), anterior (45.8%), non-granulomatous (90.8%), and recurrent (47.6%) were the most common types of uveitis found in our population sample. The most common cause of uveitis in this study was idiopathic, followed by toxoplasmosis and HLA-B27 + associated uveitis, which differs from the previous Colombian study where ocular toxoplasmosis was the most frequent cause. This highlights a significant shift from infectious etiologies to more immune-mediated processes as the cause of uveitis in Colombia nowadays. CONCLUSION: The results of this study provide a comparison between the clinical patterns of presentation of uveitis from 1996 to 2006 and the patterns observed from 2013 to 2021, enhancing awareness about the changing dynamics of uveitis in Colombia to guide a better understanding of the diagnosis, classification, and correlation with other systemic conditions of the disease.

Uveitis and nail psoriasis in a patient without articular involvement: a case report.

BACKGROUND: This study aimed to report a case of bilateral anterior non-granulomatous chronic non-infectious uveitis associated with isolated nail psoriasis without articular involvement. CASE PRESENTATION: A 55-year-old man with a history of open-angle glaucoma was referred to our uveitis and ocular immunology center with intraocular inflammation concordant with chronic non-infectious bilateral anterior non-granulomatous uveitis. At presentation, he had moderate inflammation in the anterior chamber bilaterally and lesions characteristic of nail psoriasis. Nail psoriasis was later confirmed by nail ultrasonography performed by a radiologist who specialized in psoriasis. Appropriate clinical and paraclinical assessments were conducted, ruling out all other possible causes of uveitis. The patient required dual systemic immunomodulatory therapy with methotrexate and adalimumab, topical anti-inflammatory drugs (steroidal and non-steroidal), and anti-glaucoma therapy to achieve satisfactory inflammatory and ocular pressure control. DISCUSSION AND CONCLUSIONS: This is the first report of non-infectious uveitis associated with nail compromise in a patient without other manifestations of psoriasis. Despite reports on the relationship between psoriatic disease and uveitis, there is insufficient information on clinical phenotypes associated with uveitis that could lead to later diagnosis and treatment of associated intraocular inflammation. Clinicians should be aware of all subtypes of psoriasis that increases a risk of developing uveitis in these patients.

Clinical patterns and risk factors in scleritis: a multicentric study in Colombia.

PURPOSE: This study aims to describe the clinical characteristics of scleritis in a large cohort of Colombian patients and identify factors associated with the clinical presentation. METHODS: Retrospective case series of patients with scleritis from 2015 to 2020. Clinical records were obtained from seven uveitis referral centers in Colombia. Patients with a diagnosis of episcleritis were excluded. RESULTS: We evaluated 389 patients with scleritis (509 eyes). There was a female predominance (75.6%) with a mean age of 51 ± 15 years. Most cases were noninfectious (94.8%) and unilateral (69.2%). The most frequent type of inflammation was diffuse anterior scleritis (41.7%), followed by nodular scleritis (31.9%) and necrotizing scleritis (12.3%). Systemic autoimmune diseases were found in 41.3% of patients, the most common being rheumatoid arthritis (18.5%) and granulomatosis with polyangiitis (5.9%). Polyautoimmunity was found in 10.4% of those with a systemic autoimmune disease. The most frequent treatment was systemic steroids (50.9%), followed by systemic NSAIDs (32.4%). Steroid-sparing immunosuppression was required in 49.1% of patients. Systemic autoimmune diseases were more common in patients with necrotizing scleritis and those older than 40 years of age. Best-corrected visual acuity of 20/80 or worse at presentation was more common in necrotizing scleritis and subjects with associated uveitis, ocular hypertension, or who were over 40 years of age. CONCLUSIONS: This is the first study in Colombia and the largest in Latin America describing the clinical characteristics and presentation patterns of scleritis. The most common presentation was in females, with unilateral, anterior diffuse noninfectious scleritis. Systemic autoimmune diseases and polyautoimmunity were frequent, as was the need for steroid-sparing immunosuppression. Age over 40 and necrotizing scleritis were associated with higher odds of having a systemic autoimmune disease and worse visual acuity at presentation.

Ocular Cicatricial Pemphigoid, Sjögren's Syndrome, and Hashimoto's Thyroiditis as a Multiple Autoimmune Syndrome: A case report.

PURPOSE: To present a rare and novel association of Ocular Cicatricial Pemphigoid, Sjögren's Syndrome, and Hashimoto's Thyroiditis as a Multiple Autoimmune Syndrome. CASE REPORT: A 43-year-old Colombian female, presented with corneal ulcers, associated with trichiasis. At the ophthalmological examination forniceal shortening OU and symblepharon OD was found. Conjunctival biopsy was performed, evidencing linear deposition of IgG and IgA antibodies along the basement membrane of the conjunctiva, confirming Ocular Cicatricial Pemphigoid diagnosis. After 12 years, the patient presented constitutional symptoms, xerostomia, and worsening of xerophthalmia. Laboratory tests showed positive Anti-TG, Anti-TPO, Anti-Ro, and Anti-La antibodies, and salivary gland biopsy was consistent with Sjögren's Syndrome. Due to these findings, Hashimoto's Thyroiditis and Sjögren's Syndrome were diagnosed, defining a Multiple Autoimmune Syndrome. CONCLUSION: A novel association of Multiple Autoimmune Syndrome is presented in this case. Ophthalmologists and other specialists involved in the evaluation and treatment of patients with autoimmune diseases, should be aware of this clinical presentation. A multidisciplinary approach in this condition is important for optimum treatment instauration and follow-up, in order to prevent complications.

Ocular Manifestations in Colombian Patients with Systemic Rheumatologic Diseases.

PURPOSE: To establish the prevalence of ocular involvement in a Colombian population with rheumatologic diseases. DESIGN: Observational cross-sectional study. METHODS: We included a probabilistic sample size of 797 patients who attended a rheumatologic disease center in Bogotá, Colombia. Statistical analysis with descriptive measures and Chi-square independence test between rheumatologic diseases and ophthalmological symptoms and diseases was performed. RESULTS: Eighty-four percent of the population were women, and the mean age was 54.61± 15.64 years. The most common condition was rheumatoid arthritis (33.37%), followed by fibromyalgia (22.71%), Sjögren Syndrome (19.72%), and systemic lupus erythematosus (9.91%). Almost 7% of the patients presented polyautoimmunity. Thirty-five percent of the patients reported one or more ophthalmological symptoms, being dry eye sensation the most common (30.86%), followed by ocular pain (2.76%), red-eye, and decreased visual acuity (both 2.63%). Similarly, 21.45% of the patients presented one or more ophthalmological diagnoses, being keratoconjunctivitis sicca the most common (15.93%), followed by cataract, uveitis (1.38% each), and scleritis (1.25%). CONCLUSION: Almost a third of the patients reported any ocular involvement. It is crucial to be aware of the most common ophthalmic manifestations among the different rheumatologic diseases in our population, to offer early specialist referral and timely treatment.