Purpose: To report a case of cobalt-induced retinopathy from a knee prosthesis and to outline the diagnostic challenges and management approach. Observation: A 67-year-old female presented with chronic bilateral visual disturbances, including blurred vision and photopsia, which began shortly after receiving a cobalt-containing knee prosthesis (DePuy Sigma Total Knee System, recalled by FDA in 2014, Recall No. Z-0423-2014). Ophthalmic evaluation revealed bilateral chorioretinitis, cystoid macular edema, and optic disc inflammation. Removal of the cobalt-containing prosthesis, along with aggressive immunosuppressive therapy, led to significant improvement in visual acuity and retinal function, as confirmed by fluorescein angiography, electroretinography, and Goldmann visual field testing. Conclusion: This case adds to the limited literature on cobalt-induced retinopathy by demonstrating that even small prosthetic implants, such as knee prostheses, can lead to systemic cobalt toxicity with significant ocular complications. Early diagnosis, combined with prompt removal of the affected prosthesis and management of inflammation, is crucial for restoring vision and preventing further damage.

AIMS: This study investigates the association between retinal vascular tortuosity and retinal vasculitis. METHODS: A retrospective review of medical records was conducted for 135 patients diagnosed with retinal vasculitis at our institution from June 2022 to June 2024. The presence and type of retinal vascular tortuosity were assessed, and logistic regression analysis was used to evaluate associations with viral infections, autoimmune conditions, and other clinical features. RESULTS: Of 256 patients with posterior uveitis, 135 patients were identified with retinal vasculitis, and 37 (27.4%) exhibited retinal vascular tortuosity. Specifically, 24 patients presented with arterial tortuosity, 5 with venous tortuosity, and 8 with both arterial and venous tortuosity. Logistic regression analysis revealed that arterial tortuosity was significantly associated with posterior synechiae, while venous tortuosity was primarily observed in patients with birdshot chorioretinopathy. Combined arterial and venous tortuosity was more commonly observed in patients with viral infections, toxoplasmosis, or psoriasis. Notably, after inflammation was controlled, retinal vascular tortuosity improved. However, the average recovery times varied between arterial tortuosity, venous tortuosity, and the combination of both. CONCLUSION: Retinal vascular tortuosity is prevalent in retinal vasculitis and is associated with specific infectious etiologies and clinical features. It may serve as a prognostic marker for disease severity and treatment planning.

PURPOSE:The aim of this study was to describe two cases of ocular ischemic syndrome (OIS) that were initially ruled out because of a negative carotid duplex ultrasound but eventually confirmed by angiography studies. METHODS:This is a case series. RESULTS:Case 1: A 67-year-old woman presented with symptoms suggestive of OIS, but carotid duplex ultrasound was negative, and the patient was diagnosed with occlusive retinal vasculitis due to retinal nonperfusion and vascular leakage on fluorescein angiography. Immunosuppressive therapy was initiated, but her symptoms did not improve. Computerized tomography angiography was significant for severe osteal stenosis of the aortic arch vessels. Left common carotid angioplasty and stenting resulted in complete resolution of the symptoms and vascular leakage of the left eye. Case 2: A 41-year-old man with cryoglobulinemia-associated vasculitis complained of symptoms consistent with OIS, which was initially ruled out through a negative carotid duplex ultrasound. Fluorescein angiography revealed delayed arterial filling with poor retinal perfusion. Magnetic resonance angiography revealed ophthalmic artery stenosis, which was attributed to the underlying systemic vasculitis. CONCLUSION:Computerized tomography angiography or magnetic resonance angiography should be performed to rule out OIS if duplex ultrasound is negative in the setting of high clinical suspicion. Carotid ostial and ophthalmic artery stenoses are rare but possible causes of OIS.

PURPOSE:To assess the efficacy and safety of adalimumab (ADA) injections (group 1), infliximab infusions (IFX) (group 2), and tocilizumab infusions (TCZ) (group 3) in pediatric retinal vasculitis (RV). DESIGN:Retrospective interventional case series. METHODS:Pediatric patients who were diagnosed with RV and treated with biologics (ADA, IFX, TCZ) for ≥6 months were included. A chart review of 11 patients (18 eyes), 17 patients (30 eyes), and 7 patients (11 eyes) in groups 1, 2 and 3, respectively, was performed to assess clinical characteristics, central subfield thickness (CST), and fluorescein angiography (FA) score using the Angiographic Scoring for the Uveitis Working Group (ASUWOG) system. RESULTS:Mean age was 13.5 ± 4.3 years in group 1, 11.8 ± 2.5 years in group 2, and 13.9 ± 4.1 years in group 3 (P = .332). Eight patients (72.7%, 13 eyes) in group 1 and 14 patients (82.4%, 24 eyes) in group 2 were biologic naive, whereas in group 3 all patients were treated with ADA and/or IFX prior to TCZ. Mean FA scores were significantly reduced from 6.8 ± 2.6, 13.4 ± 4.8, and 12.8 ± 4.0 at baseline to 0.9 ± 2.3, 3.6 ± 4.6, and 4.4 ± 3.9 at final visit in groups 1, 2, and 3, respectively (P < .05). Complete resolution of RV was observed in 12 (66.7%), 13 (43.3%), and 1 (9.1%) eyes; mean time to complete resolution was 11.0 ± 5.0, 13.3 ± 5.8, and 23 months in groups 1, 2, and 3, respectively. No significant adverse events were observed in any group, except hair loss in 1 patient, which led to discontinuation of IFX infusions after 20 cycles of therapy. CONCLUSIONS:ADA, IFZ, and TCZ are effective and safe treatment options for pediatric RV, as objectively shown by FA scoring. TCZ appears to be an effective therapy for patients with juvenile idiopathic arthritis-associated RV or those who have failed tumor necrosis factor-α inhibitors.

PURPOSE To investigate the incidence and ophthalmic complications of pediatric uveitis using the Korean National Health Insurance (NHI) Service database. DESIGN Nationwide population-based longitudinal cohort study. METHODS This study used the NHI database from 2005 to 2021 and included individuals <18 years of age diagnosed with uveitis on at least three separate visits between 2010 and 2014, with a five-year wash-out period and a seven-year follow-up period. All uveitis cases were classified as either anterior or nonanterior on the basis of the diagnostic code. The occurrence of ophthalmic complications during the follow-up period, and the systemic and socioeconomic associations between pediatric uveitis and its ophthalmic complications were investigated. We obtained the incidence of total, anterior, and nonanterior pediatric uveitis between 2010 and 2014; the percentage of ophthalmic complications during the follow-up period; and hazard ratios for ophthalmic complications of anterior and nonanterior uveitis. RESULTS A total of 9495 cases of pediatric uveitis (8734 cases with anterior and 761 with nonanterior uveitis) were identified, with an average annual incidence (per 10 000 children) of total, anterior, and nonanterior uveitis being 2.0, 1.8, and 0.2, respectively. The most common complications were glaucoma or presumed ocular hypertension, macular disease, and amblyopia. Patients with nonanterior uveitis had a significantly higher risk of ophthalmic complications including retinal detachment, cataract, amblyopia, and glaucoma or presumed ocular hypertension than those with anterior uveitis. CONCLUSIONS This nationwide analysis of pediatric uveitis in South Korea revealed an average incidence of 2.0 per 10 000 children, highlighting the higher risks of ophthalmic complications associated with nonanterior uveitis.

Inherited retinal diseases (IRDs) are genetic disorders characterized by progressive photoreceptor function loss, often leading to significant visual impairment. Uveitis has been increasingly recognized in the clinical course of some IRDs. Despite advances in understanding the genetic causes and pathophysiology of IRDs, gaps remain in understanding the roles of inflammation and autoimmunity in IRD and IRD-associated uveitis. This review discusses IRD-associated uveitis, including anterior, intermediate, posterior, and panuveitis, as well as complications such as cystoid macular edema and retinal vasculitis. In patients with IRD-associated uveitis, mutations affecting protein function in cilia or photoreceptor outer segments suggest a universal autoimmune mechanism triggered by the immunogenicity of shedding photoreceptor discs. Notably, in patients where uveitis is the initial sign, CRB1 mutations are often implicated, likely due to the compromised blood-retina barrier function or alterations in the external limiting membrane. Other mechanisms leading to uveitis preceding IRD diagnosis include ALPK1 mutations, which activate the proinflammatory NF-κB pathway, CAPN5 mutations, which lead to dysfunction of the innate and adaptive immune systems, and VCAN1 mutations, which elicit immunogenicity due to irregularities in vitreous modeling. Understanding these mechanisms could enhance the development of innovative treatments that target personalized inflammation pathways in IRDs.

Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab. Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors. Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p = 0.046), presence of systemic disease (91.7% vs 42.1%, p = 0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p = 0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p = 0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p = 0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p = 0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p = 0.148). Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

Introduction: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents have dramatically improved outcomes and changed treatment paradigms in NIU. Areas covered: The index article summarizes the present experience of anti-TNF-alpha agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-alpha agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-alpha drug development, and promising competitor drug candidates are discussed and evaluated. Expert opinion: Anti-TNF-alpha agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-alpha agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-alpha drug development.

OBJECTIVES:To investigate the population-based incidence of uveitis and the differences between anterior and non-anterior uveitis using the comprehensive Korean National Health Insurance Service (NHIS) database. METHODS:We extracted data of patients who visited the clinic and were diagnosed with uveitis (based on Korean Classification of Diseases) from 2010 to 2021. The incidence of uveitis, differences between the demographics, and the underlying co-morbidities of anterior uveitis, non-anterior uveitis, and control groups were investigated. RESULTS:We identified 919,370 cases with uveitis (anterior: 800,132; non-anterior: 119,238). The average incidences (per 10,000 persons) of anterior and non-anterior uveitis were 13.0 (95% confidence interval [CI], 12.9-13.0), and 1.9 (95% CI, 1.9-1.9), respectively. The incidence increased (2010: 13.0; 2019: 16.5) but decreased during the coronavirus disease (COVID-19) pandemic (2020: 15.5; 2021: 15.4). The non-anterior group was significantly associated with sex (female, odds ratio [OR]: 1.09, p < 0.0001), specific age range (40-69 years, p < 0.0001), high Charlson Comorbidity Index (p < 0.0001), high household income (p < 0.0001), and various immunologic diseases (antiphospholipid antibody syndrome, OR: 1.79, p < 0.0001; systemic lupus erythematosus, OR: 1.22, p < 0.0001; psoriasis, OR: 1.13, p < 0.0001; ulcerative colitis, OR: 1.11, p = 0.0013; tuberculosis, OR: 1.09, p < 0.0001; rheumatoid arthritis, OR: 1.05, p < 0.0001) compared with the anterior group. CONCLUSIONS:Using the NHIS database, we conducted the largest population-based epidemiological study on uveitis in South Korea to estimate its increasing incidence in the past decade (including changes during COVID-19 pandemic) as well as its anatomical distribution. Our results may be beneficial for estimating the national burden of uveitis.

PURPOSE:To describe the various ocular clinical features and visual outcomes in Tubulointerstitial Nephritis and Uveitis Syndrome (TINU). METHODS:The medical records of 13 patients (26 eyes) diagnosed with TINU were reviewed. RESULTS:Twenty-six (26) eyes of 13 patients with TINU were reviewed in this study. The median age at onset of uveitis was 14 (range, 9-45). Eight (61.5%) subjects were female. The median follow-up of patients was 30 months (range, 6-89 months). Posterior segment findings were seen in 18 eyes of 9 patients (69.2%). The most common posterior findings were optic nerve head inflammation (16 eyes, 88.8%) and retinal vasculitis (13 eyes, 72.2%). Other posterior findings included vitritis (8 eyes, 44.4%), macular edema (6 eyes, 33.3%), snowball (4 eyes, 22.2%), and chorioretinal lesions (2 eye, 11.1%). Eight patients had fluorescein angiography (FA) data available and most eyes had retinal capillary leakage (13 eyes, 81.2%) followed by optic disc staining/leakage (12 eyes, 75%). Twelve (12) patients (92.3%) were treated with immunomodulatory treatment (IMT) and/or biologics. Five patients (%38.4) required biologics to control intraocular inflammation. CONCLUSION:Posterior segment involvement may be common in patients with TINU syndrome. FA provides significant information for detecting posterior segment involvement and disease activity in TINU. The majority of patients required systemic treatment in order to control intraocular inflammation and prevent relapses.

Purpose: A unique form of retinopathy-plausibly dark without pressure (DWP) was identified during the management of pediatric patients with retinal vasculitis (RV) and described in the index case series. Methods:Forty-three consecutive pediatric uveitis patients presented to tertiary care-unit were evaluated. We assessed DWP-like lesions in pediatric patients with RV. Wide angle fundus photographs (WAFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT) images were analyzed to identify potential retinopathy. Incidence of DWP in pediatric RV patients was also analyzed. WAFP were evaluated using image-J software to measure retinopathy area (RA). Results:Twenty-six of 43 patients were diagnosed with RV and were treated. Retinopathy was detected in 20 patients (30 eyes/76.9%) during treatment. Mean age was 12.8±3.36 years; 40% were female. On WAFP, the lesions appeared as dark areas that were diffuse, mid-peripheral or peripheral. All 20 patients (30 eyes) showed hypo-autofluorescence on FAF at the same locations as the WAFP. Twelve patients (17 eyes) who had OCT images of the RA demonstrated ellipsoid zone disruption. Progression of the retinopathy overtime was analyzed in 28 eyes; all eyes showed improvement of RV with therapy. Mean RA significantly decreased from 394.67 mm2 (time of retinopathy detection) to 365.88 mm2 (last follow-up) (p=0.03). Conclusions:Pediatric RV may be associated with a retinopathy pattern described as DWP previously. Improvement in the RA may be related to improvement of disease activity, but further studies are needed to understand the underlying pathophysiology. Such findings might serve as a marker of previous/ongoing RV in pediatric patients.

Purpose: To report a case of neurosarcoidosis (NS) who was initially diagnosed as Coccidioidomycosis immitis (CI) infection. Observations: A 57-year-old diabetic man presented with sudden painless diminution of vision, metamorphopsia, and color vision deficits in the left eye (OS) for one month. His vision was 20/20 in the right eye (OD) and 20/40 OS. Ophthalmic examination revealed left relative afferent pupillary defect, blurred optic nerve margin, creamy chorioretinal infiltration around the optic disc, and mild macular edema. OD examination was non-revealing. Chest CT scan with contrast showed calcified mediastinal lymph nodes, but biopsy of the lymph nodes was normal. Brain and orbit MRI demonstrated soft tissue abnormality with enhancement in left orbital apex with involvement of the extraocular muscles. CSF culture was negative, but complement fixation had positive titer of 1:2 for CI. The patient was diagnosed with CI meningitis, and antifungal therapy was initiated. Slight visual and symptomatic improvement was observed, which was not completely satisfactory. Biopsy of extraocular orbital muscle five months later revealed non-caseating granulomatous inflammation, leading to initiation of prednisone trial therapy. Nine months later, the patient was referred to a tertiary center owing to persistence of optic disc edema OS. PET CT was consistent with a diagnosis of sarcoidosis. Antifungal treatment was discontinued, and oral prednisone with methotrexate was initiated. Subsequently, methotrexate was replaced by infliximab to further manage ocular inflammation and neurologic symptoms which was effective. Vision was 20/20 OD and 20/30 OS at the most recent visit.Conclusion and Importance: Signs and symptoms of neurosarcoidosis and coccidioidomycosis can be similar and deceiving. The index case underscores importance of considering appropriate differential diagnoses in patients with similar symptoms and signs who may respond to preliminary designated treatment but not to the optimal extent. Considering such possibility could assist clinicians in managing the patients timely and efficiently.