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Differential Composition and Structure of the Microbiota from Active and Inactive Stages of HLA-B27-associated Uveitis by Paired Fecal Metagenomes

ABSTRACT Purpose To compare the diversities and abundances of bacterial taxa in the microbiome of patients with HLA B27-positive acute anterior uveitis (AAU) in the active and inactive phases. Methods An observational descriptive prospective and comparative study was conducted in ten HLA-B27-positive AAU patients (44.6 ± 13.4 years). The microbiome of the stool samples obtained in the active and inactive stages was analyzed by sequencing the V3 region of the 16S rRNA gene. Results The differences in the bacteria profile between active and inactive stages in each individual were confirmed (p < 0.0001). Ten OTUs were found exclusively in the active phase of 90% of the individuals, suggesting a proinflammatory association. Blautia OUT_4 and Faecalibacterium OUT_2 abundances showed a direct relationship between abundance and severity of ocular inflammation. Two OTUs were exclusive of the inactive stage, suggesting an anti-inflammatory role. Conclusion The metagenomic profile of the fecal microbiota differs in the acute phase of the AAU compared to when the inflammation subsides, despite being the same individual and a short time-lapse. AAU is a fertile field for studying the connection between subtle rapid changes in microbiota and their systemic consequences.

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Predisposing Factors and Clinical-Microbiological Profile of Neonatal Corneal Ulcer: A Systematic Review and Analysis

ABSTRACT Objective To provide a comprehensive overview of predisposing factors and clinical-microbiological profile of neonatal corneal ulcer. Methods The literature search was undertaken in PubMed, SCOPUS, Embase, Web of Science, and Google Scholar databases on published papers from inception to May 31, 2023. The included articles were independently assessed for methodological quality using a Joanna Briggs Institute checklist. Weighted analysis was utilized, assigning a weight of one to each case report and a weight equivalent to the sample size for the case series/original studies. Result We included 34 relevant case reports/series and one original study. Seventy-four neonates were enrolled with a boy-to-girl ratio of 1.3:1 and a median age of 17 days (1–27 days). Prematurity and neonatal intensive care unit (NICU) care (21.6%), congenital horizontal tarsal kink (13.5%), neonatal herpes infection (13.5%), congenital entropion (5.4%), and jaundice (5.4%) were the most common potential risk factors and coexisting conditions. Microbiology evaluation showed positive results in 53.8% (21/39 cases). Viral and bacterial infections were the most common cause, followed by fungal infections. Herpes virus (18.9%), Pseudomonas aeruginosa (18.9%%) and Staphylococcus epidermidis (6.7%) were the most prevalent causative agents. Negative microbiology was significantly more common in neonates with structural abnormalities (14.9%) compared to others (6.8%) (p = 0.01). Conclusion Based on the findings of reported studies, this systematic review has increased awareness of the risk factors and etiologies that lead to developing corneal ulcers in neonates.

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Clinical and Transcriptional Profiles Reveal the Treatment Effect of Adalimumab in Patients with Initial-Onset and Recurrent Vogt–Koyanagi–Harada Disease

ABSTRACT Purpose We aimed to evaluate adalimumab efficacy in patients with initial-onset or recurrent Vogt–Koyanagi–Harada (VKH) syndrome. Methods A retrospective clinical study was performed to examine the therapeutic effect of adalimumab in 22 VKH patients,16 with initial-onset and six with recurrent VKH. Another 22 patients with initial-onset VKH who did not receive adalimumab were included as controls. The main observational parameters included the central macular thickness (CMT), subfoveal choroidal thickness (SCT), best-corrected visual acuity (BCVA), anterior chamber cell grade (ACC), glucocorticoid dose (GCD), and the development of sunset glow fundus. MRNA sequencing was used to profile the tumor necrosis factor (TNF)-α pathway in peripheral blood mononuclear cells obtained from nine patients with initial-onset VKH disease, six patients with recurrent VKH, and eight healthy controls. Results In the initial-onset group, adalimumab therapy significantly improved the BCVA, CMT, SCT, and ACC. Furthermore, adalimumab significantly decreased GCD in patients with initial-onset. In patients with recurrent VKH, the SCT significantly improved after adalimumab treatment, but no significant changes in BCVA, CMT, and ACC were observed. All six patients experienced relapse during follow-up. The TNF-α pathway exhibited a significant increase in initial-onset VKH when compared with that in both healthy controls and recurrent patients. Conversely, it was suppressed in recurrent VKH when compared with that in the initial-onset or healthy control groups. Conclusions In patients with initial-onset VKH, adalimumab effectively reduces glucocorticoid dependence. However, adalimumab may not be effective for preventing relapse or providing long-term inflammation relief in patients with recurrent VKH.

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A Rare Presentation: Bilateral Necrotizing Scleritis in Primary Sjögren’s Syndrome

ABSTRACT Purpose We report a rare and challenging case of bilateral necrotizing scleritis in primary Sjögren’s syndrome (pSS). Methods Retrospective case report. Results A 72-year-old diabetic, hypertensive female patient presented with sudden onset of painful red left eye and was noted to have a corneal ulcer with severe thinning. She was managed with topical fortified antibiotics and tissue glue and bandage contact lens. During subsequent follow-ups, she developed necrotizing scleral melts in both eyes. On investigations, antinuclear antibodies were positive in a dilution of 1:160 with 2+ speckled pattern, with antinuclear antibody line immunoassay showing anti SS-A/ Ro52 positive. In view of rapidly developing scleral thinning and impending perforation, she was started on intravenous methylprednisolone 1 g/day for 3 days, along with steroid-sparing immunomodulatory therapy (mycophenolate mofetil 500 mg twice a day). She showed a rapid response to therapy and is currently stable on tapering oral steroids and mycophenolate mofetil. Conclusion This case underscores the unique presentation of pSS, characterized by bilateral necrotizing scleritis. The favorable outcome was attained through prompt immunosuppressive intervention and a collaborative, multidisciplinary approach. Further, this case report addresses a gap in the existing literature concerning pSS-related scleritis. It also emphasizes the crucial role of a rheumatologist in the comprehensive management of this condition.

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Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Ocular Manifestations: Case Series and Literature Review

ABSTRACT Purpose To investigate the diversity of ocular manifestations in patients with positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA). Methods The clinical records of five patients exhibiting ocular manifestations and testing positive for serum MPO-ANCA were retrospectively reviewed. Results Three out of five patients were female. The youngest patient was aged 26, whereas the eldest was 83 years old. 80% (n = 4) of them had purely anterior segment involvement, with the commonest manifestation being peripheral ulcerative keratitis and scleritis. Only one patient had posterior segment involvement, specifically posterior ischemic optic neuropathy. Two patients demonstrated unilateral involvement. There was only one patient diagnosed with systemic involvement, presenting as mixed nephrotic and nephritic syndrome, who required a course of intravenous methylprednisolone during the active stage. Three patients required second-line immunosuppressants throughout the course due to frequent relapse. Conclusion Anterior segment ocular manifestations are not uncommon and can be the initial presentation of p-ANCA-associated vasculitis (AAV). Therefore, its evaluation should be considered in establishing the diagnosis of AAV, a life-threatening disease.

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Janus Kinase Inhibitors as a Third-Line Therapy for Refractory Endogenous Noninfectious Uveitis

ABSTRACT Purpose Janus kinase (JAK) inhibitors have recently been used to treat patients with biologic refractory noninfectious uveitis (NIU). This narrative review updates the current evidence relevant for their application in patients with refractory NIU. Methods A literature search was performed for articles published until October 2023 in the PubMed, Scopus, and CENTRAL databases using the key terms “noninfectious uveitis” and “Janus kinase inhibitor” or “JAK inhibitor” without any exclusion criteria. Published articles were selected based on their clinical focus, relevance for ocular disease, time since publication and study design reflecting their scientific soundness with a critical appraisal of drug safety aspects. Results Janus kinases are transmembrane signaling proteins. Their inhibition has shown therapeutic potential experimentally and in patients with multiple immune-mediated diseases, including NIU. JAK inhibitors differ from biological agents in that they inhibit not one specific but multiple cytokines. These agents can be ingested orally and seem superior to adalimumab for most indications. While there is no doubt regarding their efficacy in treating immune-mediated inflammatory diseases, reports regarding their safety are increasing, and the findings are generally confusing and contradictory. Since substantiated information about their specific safety profiles in patients with inflammatory eye disease is lacking, their position in the therapeutic algorithm for uveitis has yet to be determined. Conclusions In the absence of evidence from controlled clinical trials, JAK inhibitor therapy is still rendered experimental and currently considered only for sight-threatening uveitis. JAK inhibitors may be considered for specific NIU entities for which there is insufficient response or secondary loss of response to conventional or biologic disease-modifying drugs.

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Unveiling Key Pathological Indicators for Disease Progression in Vogt Koyanagi Harada Disease and Sympathetic Ophthalmia Through Advanced Choroidal Volume Analysis

ABSTRACT Purpose To evaluate the association between quantitative parameters derived from volume analysis of optical coherence tomography (OCT) data and disease worsening in Vogt-Koyanagi-Harada disease (VKHD) and sympathetic ophthalmia (SO). Methods This retrospective study, conducted at Osaka University Hospital, employed swept-source OCT scans from patients diagnosed with VKHD or SO between October 2012 and January 2021. The choroidal vessel structure was segmented and visualized in three dimensions, generating quantitative vessel volume maps. Region-specific choroidal vessel volume (CVV), choroidal volume (CV), and vessel index (VI) were scrutinized for their potential correlation with disease severity. Results Thirty-five eyes of 18 VKHD and 2 SO patient (8 females, 10 males) were evaluated. OCT-derived CVV maps revealed regional CV alterations in VKHD and SO patients. Two parameters, i.e. CV at 3- and 6-month follow-ups (p = 0.044, p = 0.040, respectively, with area under the ROC curve of 0.70) and CVV at 6 months (p = 0.046, area under the ROC curve of 0.71), were significantly higher in recurrent VKHD and SO compared to effectively treated cases. Conclusions The volume analysis of OCT images facilitates a three-dimensional visualization of choroidal alterations, which may serve as a reflection of disease severity in VKHD and SO patients. Furthermore, noninvasive initial CVV or CV measurements may serve as potential biomarkers for predicting disease recurrence in VKHD and SO.

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Evaluation of Choroidal Thickness and Choroidal Vascularity Index in Patients with Rheumatoid Arthritis

ABSTRACT Purpose To evaluate the choroidal vascularity index and choroidal thickness in patients with rheumatoid arthritis. Method This study is a case control study. Our study consists of a total of two groups, with 32 individuals diagnosed with rheumatoid arthritis (RA) and 32 healthy volunteers. The thickness of the subfoveal choroid was measured from the 500 micron (µm), 1000 µm, 1500 µm nasal aspect of the fovea, and 500µm, 1000µm, 1500 µm temporal and subfoveal thickness of the fovea. ImageJ version 1.53i (National Institutes of Health, Bethesda, MD, USA) from open access was used for choroidal vascular index calculation. Results The mean age (p = 0.064) and gender distribution (p = 0.522) were not statistically different between these two groups. There was no difference between the groups in terms of visual acuity (p = 0.060), intraocular pressures (p=0.056), refractive errors (p = 0.418), and axial lengths (p = 0.280). Temporal 500 µm CT (p = 0.038), temporal 1000 µm CT (p = 0.010), and temporal 1500 µm CT (p = 0.005) differed significantly between the groups. The luminal area was significantly different between the RA group (842.71 ± 192.77) and the control group (957.78 ± 230.83) (p = 0.034). The choroidal vascularity index showed a significant difference between the RA group (64.99 ± 4.71) and the control group (67.34 ± 3.40) (p = 0.026). A significant difference was observed between the seronegative RA and the control group with temporal 1500 µm CT (p = 0.030), temporal 1000 µm CT (p = 0.023), and luminal area (p = 0.034). Conclusion We demonstrated thinning in CT and decreased CVI for the first time in RA patients by comparing it with the control group.

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