Ocular Immunology and Inflammation最新文献

Purpose: Intermediate uveitis (IU) can occur secondary to systemic autoinflammatory disorders, such as juvenile idiopathic arthritis and multiple sclerosis. In contrast, pars planitis (PP) specifically refers to an idiopathic form of IU, characterized by the absence of any identifiable underlying systemic condition. The frequency of the association between PP and CNS demyelination is unknown in children.

Methods: A retrospective analysis of paediatric PP patients' clinical and brain magnetic resonance imaging (MRI) data was conducted to investigate the coexistence of PP and CNS demyelinating pathologies in children.

Results: The cohort comprised 65 paediatric patients with PP, mean age 13.25 ± 3.1, (range 6-18, median 13) years, 41.5% female, who had at least one brain MRI. The mean follow-up was 4.02 ± 2.76 (range 0.5-11, median 4) years. Demyelinating lesions on MRI were visible in 5/65 (7.7%) patients. None reported neurological symptoms nor had abnormal findings on neurological examination. Three patients who had been undergoing adalimumab (ADA) treatment for a period of between three months and four years had their ADA therapy stopped when a demyelinating lesion was observed on MRI. Additionally, mycophenolate mofetil or methotrexate treatment was maintained as a maintenance therapy. The other two patients had not received any immunomodulatory treatment when demyelinating lesions were identified, and MRI findings were taken into consideration when treatment was planned.

Conclusions: Demyelinating lesions of the CNS can be detected in paediatric PP patients at a rate similar to adults. Clinicians should be aware of the presence of silent demyelination in PP and plan the anti-inflammatory treatment accordingly.

Purpose: Non-infectious uveitis (NIU) is a major cause of visual loss among young adults, and the available therapies are limited. Adalimumab (ADA), an antibody targeting tumour necrosis factor α (TNF-α), is an effective treatment. This review aims to examine immunogenicity of ADA, and its association with serum ADA trough levels (SATL) and the risk of treatment failure.

Methods: A systematic review of the literature was conducted, following PRISMA guidelines. Studies published between 2019 and 2023 were included. After applying the inclusion criteria, 10 articles were selected. The risk of bias was evaluated using the most appropriate method for each type of study.

Results: In total 10 studies were finally included. Most of the investigation reported the formation of anti-ADA antibodies (AAA), which was associated with low SATL and poor treatment response. Some studies also distinguished between transient and permanent AAA, with transient AAA linked to a higher risk of treatment failure. Risk factors for AAA development were explored, with many studies highlighting the benefits of combined therapy with ADA and other immunosuppressants compared with ADA monotherapy.

Conclusion: The association between low SATL, AAA, and poor response to ADA treatment is well established. However, further high-quality investigations are needed to strengthen the evidence in this area. Therapeutic monitoring strategies appear to be valuable tools for providing personalized management for patients with NIU.

Aim: To evaluate the safety and preliminary efficacy of low-dose subconjunctival adalimumab in patients with non-infectious uveitis (NIU), refractory to conventional immunomodulatory therapy (IMT).

Methods: Prospective, noncomparative, interventional case series. Five patients with bilateral panuveitis (four post-therapeutic vitrectomy) and persistent intraocular inflammation on conventional IMT for > 2 years received three doses of subconjunctival adalimumab 5 mg/0.1 mL at two-week intervals and followed up for 24 weeks.

Results: No cases of persistent conjunctival congestion, corneal erosions or infection, or intraocular pressure > 21 mmHg were noted. Improvement in inflammatory scores and best-corrected visual acuity (BCVA) were noted in three patients each and worsening in none. None of the three patients who showed initial improvement in visual acuity had any baseline cystoid macular edema or vitreous haze to account for the improvement in BCVA.

Conclusion: Subconjunctival administration of 5 mg adalimumab is a safe and effective therapy for NIU refractory to conventional IMT.

Purpose: To assess the efficacy and safety of weekly adalimumab after dose escalation in patients with chronic refractory non-infectious uveitis.

Methods: A retrospective analysis was conducted on patients aged 18 years and older with persistent chronic uveitis despite bi-weekly adalimumab treatment. Data collected included uveitis diagnosis, anatomical site of involvement, history of immunosuppressive treatments, relapse frequency, and other relevant clinical parameters.

Results: This study included 30 patients (18 females and 12 males) with a median age of 33.5 (22-57) years and a mean follow-up period of 62.6 ± 25.2 months. Median visual acuity was 0.29 logMAR (0.22-0.40) with bi-weekly adalimumab treatment and improved to 0.20 logMAR (0.10-0.36) with weekly adalimumab treatment (p = 0.009). A significant reduction in central macular thickness was observed with weekly adalimumab treatment compared to the bi-weekly regimen (259.67 µm vs. 336.47 µm, p = 0.001). The frequency of relapses was 1.9 ± 0.66 with bi-weekly treatment and 0.53 ± 0.33 with weekly treatment (p = 0.001). The proportion of patients exhibiting active ocular inflammation requiring systemic steroids was 60% in the bi-weekly treatment, compared to 24.3% in the weekly treatment. In terms of adverse effect profile, both treatment modalities exhibited similar characteristics. Weekly adalimumab is associated with a significantly reduced risk of relapse compared with bi-weekly ADA (HR = 0.267, p = 0.001).

Conclusion: Weekly adalimumab treatment is a viable option for managing inflammation in refractory uveitis, providing enhanced efficacy to the standard dose in terms of visual and anatomical outcomes, while maintaining a comparable side effect profile.

Purpose: This study aimed to evaluate the efficacy of methotrexate (MTX) treatment in pediatric non-infectious uveitis (NIU) cases.

Methods: Patients diagnosed with pediatric NIU and initiated on subcutaneous MTX at a dose of 10 mg/m²/week between 2023 and 2025 were included in the study. The patients' age, age at uveitis diagnosis, anatomical localization and etiology of uveitis, baseline and final best-corrected visual acuity (BCVA), and anterior and posterior segment complications detected at the initial visit were recorded.

Results: A total of 127 eyes from 64 patients were included in the study. Of these patients, 39 were female, and 25 were male. The mean age was 9.89 ± 3.56 years (3-17 years). At the initial visit, at least one ocular complication in at least one eye was detected in 49 patients. Remission was achieved in 23 cases with MTX treatment, whereas 41 patients did not achieve remission. Among the 49 patients with at least one ocular complication, remission was achieved in 13 with MTX treatment. In contrast, among the 15 patients without any complications, remission was achieved in 10 (p = 0.005). The risk of non-responsiveness to MTX treatment was found to be 10.7 times higher in patients with at least one ocular complication at diagnosis.

Conclusion: MTX is an effective and safe treatment for pediatric NIU. However, in a significant proportion of patients, particularly those with ocular complications, MTX alone may be insufficient, necessitating the addition of other immunosuppressive agents.

Purpose: To investigate the clinical characteristics, risk factors, and prognostic factors of cytomegalovirus retinitis (CMVR) after hematopoietic stem cell transplantation (HSCT).

Methods: A retrospective cohort study was conducted involving 473 HSCT patients (193 allogeneic, 280 autologous) from 2019 to 2023.

Results: In this cohort, 12 patients (21 eyes) developed CMVR. The cumulative incidence was 2.54%. CMVR was bilateral in 75% of cases, with a mean onset of 136.4 ± 59.1 days post-transplantation. CMV DNA was detected in 88.9% (16/18) of aqueous humor samples. Retinal detachment was the most common complication, affecting 52.4% of eyes. All patients had three or more risk factors. Median visual acuity declined from 20/80 (range, hand motion-20/20) initially to 20/125 (range, no light perception-20/25) at final follow-up. CMVR was the first symptom of CMV infection in 16.7% of cases. The recurrence rate was 25.00% (3/12), with recurrent cases linked to EBV viremia episodes. Correlation analysis revealed that CMVR type and initial BCVA were significantly associated with RD (p < 0.05).

Conclusions: These findings highlight the critical importance of the first year post-HSCT for CMVR detection. Increased ophthalmic screening is advised for patients with multiple risk factors and hemorrhagic types to improve outcomes.

Purpose: To report a case of Ocular Whipple's Disease (WD) that presented as chronic bilateral uveitis and to highlight the essential role of molecular diagnostics in reaching a definitive diagnosis.

Methods: This report describes the case of a 67-year-old female with chronic, refractory uveitis. The patient underwent a diagnostic vitrectomy. The collected vitreous sample was analyzed using histopathology with Periodic Acid-Schiff (PAS) staining, transmission electron microscopy (EM), and polymerase chain reaction (PCR) for Tropheryma whipplei.

Results: Histopathology of the vitreous revealed bubbly histiocytes containing PAS-positive granules, and EM confirmed the presence of Tropheryma whipplei bacteria. PCR analysis of fresh vitreous fluid yielded a positive result for T. whipplei 16S rRNA. In contrast, systemic evaluation, including a duodenl biopsy, was negative for WD. Following treatment with appropriate antibiotics, the patient's ocular inflammation resolved, and visual acuity improved significantly.

Conclusion: Ocular WD should be considered in the differential diagnosis for chronic, unexplained uveitis, even when systemic symptoms are absent. PCR analysis of vitreous fluid is an invaluable tool for confirming the diagnosis and is crucial for guiding appropriate, sight-saving therapy.

Purpose: To characterize the course of uveitis in ulcerative colitis (UC) patients following colectomy and assess whether uveitis activity arises and/or persists independently of colonic disease.

Methods: This is a retrospective case series from a tertiary uveitis referral center. Patients with non-infectious uveitis, a confirmed diagnosis of UC, and a history of colectomy were included. Clinical data were extracted, including demographics, ocular history, treatment regimens, and disease activity. Uveitis flares were defined as the presence of at least 1+ cells or flare in the anterior chamber, 1+ vitreous cells and/or haze or angiographic evidence of active inflammation as noted by the investigators.

Results: We identified 73 patients with UC-associated uveitis and 11 had a history of colectomy. Post-colectomy uveitis flares occurred in all 11 patients. Notably, eight patients experienced de novo uveitis activity following their colectomy. The remaining three uveitis patients had documented uveitis flares prior to colectomy. A total of 25 flares were documented, including multiple recurrences in three patients. One patient experienced 13 flares and ultimately required enucleation. Excluding this difficult case, patients with long-term follow-up (≥1 year) generally responded to topical steroid therapy. However, several flares occurred despite concurrent immunomodulatory therapy.

Conclusion: This case series highlights that uveitis flares may persist or recur following colectomy in UC patients, supporting the hypothesis that uveitis activity can occur independently of intestinal inflammation. These findings support the need for continued ophthalmologic surveillance in UC patients post-colectomy.

Purpose: Adalimumab (ADA) is the only biologic agent approved for treating non-infectious uveitis (NIU). Anti-drug antibodies (AAA) may be an essential factor associated with treatment failure. We conducted a study to determine the clinical response to ADA treatment in patients with NIU. We also aimed to determine AAA's frequency and clinical importance in these patients.

Methods: This cross-sectional study included 60 NIU patients who used ADA therapy every other week or weekly for at least three months. The clinical findings recorded before starting ADA and on the day included in the study were compared. Serum AAA formation was evaluated. AAA-positive and AAA-negative patients were compared in terms of etiology, duration, and localization of uveitis, duration of ADA treatment, and additional IMT.

Results: The increase in visual acuity, decrease in central macular thickness, improvement in the number of attacks/year, and decrease in need for CS were statistically significant with ADA treatment. AAA was positive in 15 (25%) patients. The improvement in median visual acuity, CMT, and number of attacks/year was statistically significant in both ADA-positive and negative patients. The effect of disease etiology, disease duration, uveitis localization, ADA treatment duration, and additional IMT use on serum AAA formation could not be demonstrated.

Conclusion: ADA is mostly associated with favorable clinical response in treating NIU. In insufficient clinical response, the dose escalation method may increase treatment success. AAA formation may not be the only factor in the ineffectiveness of treatment.

Purpose: To study the clinical presentation, outcomes, and factors affecting the final visual outcome of Vogt-Koyanagi-Harada (VKH) disease in the pediatric age group.

Methods: Pediatric patients who were diagnosed with VKH at King Khaled Eye Specialist Hospital (KKESH) between 2007 and 2024. Demographic and clinical data were collected and analyzed for an association with the final visual outcome.

Results: Sixty-nine children (138 eyes) with an age range upon presentation from 2 years old to 18 years old and a mean age of 12.2 ± 4.0 years were included. The mean duration of follow-up was 6.5 ± 3.1 years. There were 35 (50.7%) males and 34 (49.3%) females. Sixty children (86.9%) had initial-onset acute VKH, while 9 children had chronic recurrent VKH. At initial presentation, the mean LogMAR BCVA was 0.6 (Snellen = 20/70) ± 0.6. Children with chronic recurrent VKH presented at an earlier age (p = 0.003), had more severe corneal involvement (p < 0.001) and more severe AC reaction (p < 0.001). Cataract developed in 33 (23.9%) eyes, 54 eyes (39.1%) developed glaucoma, and 36 eyes (26.1%) developed choroidal neovascular membranes (CNVM). Children with chronic recurrent VKH disease had higher rates of pre-existing or developing cataract, glaucoma, and CNVM. On the last visit, the BCVA improved from an average of 20/70 to 20/50. The visual improvement was statistically significant (p = 0.005).

Conclusions: Good visual outcomes can be achieved in the majority of pediatric patients with VKH disease. Children with chronic recurrent VKH disease present with more aggressive anterior segment inflammation, have higher risk of developing ocular complications, and less favorable visual outcomes.