搜索结果：Ocular immunology and inflammation

Under normal physiological conditions, tear polymorphonuclear neutrophils (PMNs) collected from the ocular surface after prolonged eye closure at night exhibit a distinct phenotype from circulating PMNs. While leukocytes have been previously observed in tears of individuals suffering from ocular allergies, limited knowledge exists on tear PMNs activation. This pilot study aims to investigate the phenotype of tear PMNs collected from participants with seasonal ocular allergy. Ten participants experiencing symptoms of ocular allergy were recruited and age- and gender-matched with 10 healthy participants. Participants were asked to collect cells using a gentle eyewash protocol immediately following a full night of sleep in the morning on Day 1 and at the end of the day on Day 2. After cell count, tear leukocytes were activated with N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) or left unstimulated. Samples were stained with antibodies against degranulation markers (CD66b, CD63), adhesion markers (CD11b, CD54), eosinophil marker (CD193), and aging marker (CD184), and analysed by flow cytometry. Significantly more tear leukocytes were collected after a night of sleep from participants with ocular allergy compared to healthy participants (p = 0.024), while there was no difference in late afternoon collections. Tear PMNs from ocular allergy patients also exhibited a less activated baseline phenotype but a higher activation potential in response to fMLP. This study indicates that the ocular environment in seasonal allergy affects the recruitment and activation of tear PMNs. Further research is needed to understand the role of tear leukocytes in ocular surface homeostasis and inflammation.

To investigate the regional epidemiological characteristics, immune mechanisms, and potential therapeutic strategies for fungal keratitis (FK) in order to provide evidence for improving patient outcomes. Clinical data from 145 patients diagnosed with FK between 2018 and 2024 were collected to analyze epidemiological features and predisposing factors. Aqueous humor (AqH) and peripheral blood samples from a subset of patients underwent flow cytometric analysis and cytokine profiling, with glaucoma patients serving as controls. The composition, function, and cytokine profiles of immune cells in the AqH of FK patients were characterized to elucidate the ocular immune microenvironment. The majority of FK patients were middle-aged and elderly males (male-to-female ratio: 1.9:1), with agricultural injuries representing the predominant etiology (73.10%) and Fusarium species identified as the leading pathogen (44.12%). Peak incidence occurred in October and November, coinciding with local harvest activities. In the AqH, neutrophils were the predominant infiltrating cells (81.25%), accompanied by a significantly elevated proportion of B cells (30.70%) and marked reductions in both the proportion and function of T cells and NK cells. Concentrations of IL-6 and IL-8 in the AqH were approximately 20-fold and 200-fold higher, respectively, than in controls. Immunosuppressive cell populations, including regulatory B (Breg) cells, activated regulatory T (Treg) cells, and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), were significantly expanded. Additionally, hyperglycemic patients exhibited heightened inflammatory responses, with significantly elevated concentrations of pro-inflammatory cytokines (IL-4, IL-6, IL-8, and TNF-α) in their AqH compared with normoglycemic patients. FK in this region is strongly associated with agricultural activities. Patients demonstrated diminished adaptive immune function alongside expansion of immunosuppressive cell populations, resulting in an ocular microenvironment characterized by suppressed adaptive immunity coexisting with enhanced innate immune responses. IL-6 may play a central role in shaping this immunosuppressive microenvironment by amplifying pro-inflammatory responses and inhibiting T cell function. Hyperglycemia appears to further exacerbate immune dysregulation, potentially impacting prognosis. Early therapeutic targeting of IL-6 may represent a strategy to alleviate ocular inflammation and reduce complications in FK; however, this hypothesis requires validation in future studies.

This review aims to describe the key mechanisms behind ocular immune privilege and how disruption of this immunological balance contributes to ocular disease. A narrative review of the literature was performed focusing on ocular immune privilege and diseases in which these mechanisms are altered. The review considered evidence related to corneal transplantation, peripheral ulcerative keratitis, age-related macular degeneration, autoimmune uveitis, diabetic retinopathy, ocular tumors, and allergic conjunctivitis. The reviewed literature demonstrates how ocular immune privilege is maintained mainly by a combination of anatomical barriers, local immunomodulatory mediators, regulatory immune-cell interactions, and ACAID-mediated systemic tolerance. Across the ocular conditions reviewed, disease was generally associated with partial disruption, remodeling, or exploitation of these mechanisms rather than complete loss of immuneprivilege. These alterations varied according to the affected ocular compartment and clinical context, but recurrently involved disruption of immune homeostasis, increased inflammatory signaling, altered leukocyte activity, impaired barrier integrity, and reduced local immune restraint. Overall, the evidence supports ocular immune privilege as a dynamic system that is not absolute, preserving ocular homeostasis under normal conditions but contributing to disease when its protective mechanisms are disrupted. Ocular immune privilege is best understood as a protective but conditional state. Its disruption does not entirely explain most ocular diseases by itself, but it helps illustrate why inflammation, transplantation, tumors, allergy, and other pathologies can behave differently in ocular tissues. Recognizing which elements are preserved or lost in each setting may improve understanding of ocular pathology and support more precise immune-directed approaches.

The safety profiles of high-dose intravitreal anti-vascular endothelial growth factor (VEGF) agents remain incompletely characterized. This study aimed to compare ocular adverse events, especially intraocular inflammation, associated with brolucizumab, faricimab, and 8 mg aflibercept. Adverse event reports for high-dose anti-VEGF agents were extracted from the FDA Adverse Event Reporting System (FAERS) database. After data standardization, quantitative signal detection analyses were performed using multiple pharmacovigilance tools. Clinical characteristics and time-to-onset profiles of adverse events were also assessed. Among 8,470 reports where high-dose anti-VEGF agents were designated as primary suspects, intraocular inflammation (IOI) was the primary adverse reaction. The strongest signals were: retinal vasculitis with brolucizumab (retinal perivascular sheathing; reporting odds ratio (ROR) = 7,451.51 [95% CI: 4,528.22- 12 261.99]), vitritis with faricimab (ROR = 655.54 [95% CI: 548.85-782.95]), and anterior chamber inflammation with 8 mg aflibercept (anterior chamber cells: ROR = 1,749.13 [95% CI: 1,149.34-2,661.92]). Using Standardized MedDRA Queries (SMQ) analysis, adverse events associated with IOI were classified into four phenotypes: anterior chamber inflammation, vitritis, retinal vasculitis, and non-infectious endophthalmitis not otherwise classified, and the results showed a descending gradient of signal strength in all phenotypes: brolucizumab exhibited the strongest signals, followed by aflibercept 8 mg, then faricimab. IOI profiles differ significantly among high-dose anti-VEGF agents. Comprehensive evaluation of individual patients' risk factors is recommended to guide clinical decision-making.

Treatment‑refractory uveitis can lead to vision‑threatening sequelae if not adequately controlled. We present a summary of previously published cases and describe the response and progression of 12 novel patients after starting off-label upadacitinib (UPA) (JAK-1 inhibitor) as a second- or third-line treatment for various uncontrolled non-infectious uveitides. Retrospective case series from a rheumatology clinic within a single Canadian city. Control of ocular inflammation, as determined by the amount of additional systemic and topical immunomodulators required to achieve quiescence, frequency of flares, or severity of inflammation, is described herein. Ten of the 12 participants were women (83.3%), and the sample had a mean age of 48.3 years (range 31.0-75.0 years). Five patients (41.7%) achieved complete control of inflammation, two of whom were able to discontinue all other systemic and topical immunomodulatory therapies for ocular inflammation and continue UPA use as of publication. An additional three patients (25.0%) achieved only partial control of ocular inflammation. The final four patients (33.3%) completely failed to respond to the medication (no change in uveitis). Ultimately, four patients (33.3%) had to discontinue UPA: two whose uveitis did not respond, and two despite good ophthalmic results. The use of UPA off-label can be transformative for the management of ocular inflammation in only select cases. We are the first to document treatment failure. A prospective, comparative, blinded trial is required to draw reliable conclusions about the perfect candidate for therapy initiation. Our observations may help providers and patients anticipate potential treatment outcomes.

To evaluate the relevance of autoantibodies to carbonic anhydrase 6 (CA6), parotid secretory protein (PSP) and salivary gland protein 1 (SP1) on dry eye disease (DED) symptoms and signs. A retrospective study of 115 individuals diagnosed with DED and tested for CA6, PSP and SP1 antibodies at the Miami Veterans Eye Clinic. Antibody status (positive: &#x2265;1 antibody &#x2265;20 EU/mL vs negative: all antibodies <20 EU/mL) and levels were analysed against DED metrics at baseline and follow-up (67 individuals). Of 115 individuals, 73 were antibody positive, with CA6 IgG most frequently elevated. Antibody-positive individuals had more severe DED symptoms (Ocular Surface Disease Index 56.64&#xb1;22.56 vs 43.89&#xb1;20.36, p=0.002) and greater tear film instability (5.38&#xb1;3.52 vs 6.83&#xb1;4.01&#x2009;s, p=0.046). These associations remained significant in forward regression analyses. Quantitative antibody levels also related to ocular signs at baseline: corneal staining to SP1 IgA (r=0.36, p<0.001) and PSP IgM (r=0.19, p=0.04) and Schirmer scores to CA6 IgG (r=-0.19, p=0.04). At follow-up, 43% (n=29) showed an increase in DED symptoms and 82% (n=55) in at least one sign, with PSP IgM being most predictive for worsening DED status. Our study suggests that CA6, PSP and SP1 antibody status and levels are relevant in DED. Antibody positivity correlated with more severe baseline symptoms and signs and individual antibody values predicted progression. Rather than markers of a systemic diagnosis, these autoantibodies may better reflect ocular disease severity and progression.

Neutrophils (polymorphonuclear neutrophils, PMNs) represent 60% of the total leukocytes in the blood, playing an essential role in innate immune defence. PMNs were originally considered to be homogenous, but a growing body of evidence suggests that they exhibit considerable heterogeneity and express various phenotypes in different tissue types under physiological and pathological conditions. This review provides an overview of the PMNs phenotypes found in various human tissues, including the lungs, female reproductive tract, mouth, and eyes, under both physiological and pathological conditions. PMNs collected from the ocular surface after prolonged eye closure, termed 'tear PMNs', represent an emerging area of research in ocular immunology and inflammation. Their potential origin, diurnal-nocturnal pattern and functions, and their role in ocular complications are also presented and discussed.

Vision-threatening ocular diseases are impacted by aging-associated molecular changes, including mitochondrial dysfunction, cellular senescence, and chronic inflammation. Anti-VEGF therapies targeting VEGF-A/VEGFR2 signaling remain the frontline standard of care, but many patients exhibit suboptimal or nondurable responses, often due to compensatory and/or compromised antiangiogenic and anti-inflammatory pathways. We aimed to elucidate shared mechanisms underlying treatment failure and disease progression. We applied an integrative systems biology framework that combined multiomics datasets, network-based machine learning, and disease-specific pathway mapping. A comprehensive literature review of conditions, including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and aging, identified 14 core genes consistently associated with angiogenesis, inflammation, and immune signaling. Multialgorithm centrality and enrichment analyses reconstructed disease-specific interaction networks, revealing consensus mechanistic axes. Integration of cell-type-specific single-cell RNA sequencing data from AMD-RPE clusters identified cluster-specific gene hubs and vertical signaling axes, leading to VEGF blockade failure. EGFR, HSP90AA1, SIRT1, and STAT3 emerged as central resistance hubs linking angiogenesis and inflammatory processes. Pathway enrichment analyses revealed 21 conserved core signaling cascades, grouped into six functional categories, with AGE-RAGE, PI3K-Akt, HIF-1, MAPK, and chemokine pathways playing central roles. A MiRGD-based peptide nanocomplex delivering htsFLT01 achieved efficient RPE transfection and controlled gene activation under basal conditions. This systems-level framework clarifies mechanisms of VEGF blockade resistance and provides a rational basis for next-generation, combinatorial therapeutic strategies requiring validation in disease-relevant models.

Anti-vascular endothelial growth factor (VEGF) therapy has emerged as an important adjunct in the management of uveitis, particularly for complications driven by vascular permeability and ischemia, such as uveitic macular edema, inflammatory choroidal neovascularization, and retinal neovascularization (RNV). By directly neutralizing VEGF, these agents offer rapid anatomical improvement and visual stabilization, especially in patients who are steroid-intolerant or present with refractory disease. Although current evidence is largely derived from small series and observational data, the accumulating clinical experience highlights a meaningful therapeutic role for anti-VEGF agents when used in conjunction with appropriate immunosuppression or antimicrobial therapy. Emerging roles extend to inflammatory RNV, tubercular granulomas, and serous retinal detachment. However, sterile intraocular inflammation, vasculitis, and rare endophthalmitis remain important safety concerns. Evolving delivery strategies, including sustained-release formulations, posterior sub-Tenon and exploratory topical approaches, may further expand their utility while improving safety. This review synthesizes current evidence, mechanistic insights, and future directions for integrating anti-VEGF therapy in uveitis care.

The aim of the study was to analyze the epidemiological, clinical and imaging characteristics of patients with inflammatory exudative retinal detachment (ERD). This multicenter, retrospective, observational study enrolled patients with a diagnosis of an inflammatory ocular disease associated with ERD. In all patients a complete ophthalmological evaluation was performed, with best-corrected visual acuity (BCVA), automated refraction, slit lamp biomicroscopy, intraocular pressure (IOP), fundus examination, optic coherence tomography (OCT) scan, color fundus photography, fluorescein angiography (FA) and indocyanine green angiography (ICGA). ERD was located (posterior pole, peripheral retina or both) with imaging, and the presence or absence of subfoveal neuroepithelial detachment, retinal pigment epithelium (RPE) detachment, epiretinal membrane (ERM), and macular edema (ME) were documented. 130 patients were enrolled, with a mean age of 52.14&#x2009;&#xb1;&#x2009;20.69&#x2009;years. The most representative diagnosis was Vogt-Koyanagi-Harada (VKH) disease (23.85%), followed by Sarcoidosis (16.15%), Tuberculosis (13.08%) and Posterior Scleritis (PS) (9.23%). The principal location of ERD in the 165 enrolled eyes was in the posterior pole. In VKH, ERD was located at the posterior pole in 45 eyes, with 85.71% of subfoveal neuroepithelial detachment and choroidal granulomas in 87.76% of eyes. In PS a posterior pole location of ERD was found in 66.67% of eyes, with 83.33% of subfoveal neuroepithelial detachment and no choroidal granulomas. ERD is most frequently associated with VKH disease and the predominant localization is at the posterior pole, which occurs in the setting of posterior uveitis, panuveitis, and/or scleritis.

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with a worse systemic prognosis compared to methicillin-sensitive S. aureus (MSSA). Prior studies of MRSA and MSSA endophthalmitis group endogenous and exogenous cases. We performed a retrospective cohort study comparing ocular outcomes in endogenous and exogenous MRSA and MSSA endophthalmitis, representing the largest series to date (n&#x2009;=&#x2009;46 eyes). Endophthalmitis cases from October 2008-April 2025 were identified using ICD10 codes for endophthalmitis and Staphylococcus aureus. Cases with endophthalmitis diagnosis, culture-proven MRSA or MSSA and visual exams at presentation and within 3&#x2009;months were included. Of 651 potential cases, 37 cases (46 eyes) met criteria, including 7 exogenous and 30 endogenous cases. Visual acuity was categorized as &#x2264;20/200, >20/200 to &#x2264;20/40, >20/40. Complications were analyzed per eye. Categorical variables were compared with a Fisher's t-test (p&#x2009;<&#x2009;0.05). Vision at presentation, 1&#x2009;week-2&#x2009;months, and 2-3&#x2009;months did not differ significantly between MRSA and MSSA in exogenous or endogenous groups. The exogenous cohort had significantly higher rates of enucleation/evisceration than the endogenous cohort. Intravenous drug use and mortality were more frequent among patients with endogenous MRSA, though not statistically significant. MRSA and MSSA endophthalmitis have similar ocular outcomes. In exogenous and endogenous cohorts, there were no significant differences in vision or complications between MRSA and MSSA endophthalmitis except that the exogenous group had a significantly higher rate of enucleation/evisceration, potentially reflecting increased organism load with direct inoculation. The higher mortality associated with endogenous MRSA infections, though not statistically significant, warrants future investigation.

This study aimed to determine the prevalence of glaucoma in adult Japanese patients with uveitis and to assess its comorbidity according to the etiology, anatomical classification, and specific disease entities. The relationship between intraocular pressure (IOP) fluctuation and progression of uveitic glaucoma (UG) was also investigated. Adult patients (&#x2265;20&#x2009;years at onset) with uveitis treated at Hiroshima University Hospital between July 2009 and June 2023 were included. Data on etiology, anatomical classification, presence of UG, and glaucoma surgery were collected. Disease progression, defined as the slope of the mean deviation (MD) over time, was analyzed in relation to IOP fluctuation (defined as the standard deviation of all IOP measurements/eye). Among 671 patients, 212 (31.6%) had UG and 93.9% had chronic uveitis. Anterior uveitis was the most frequent type (34.4%). Non-infectious causes accounted for 86.3%, with mainly idiopathic (51.4%), sarcoidosis (13.2%), and Vogt-Koyanagi-Harada disease (12.3%). Cytomegalovirus (CMV) anterior uveitis was the most common infectious cause (3.3%). Glaucoma occurred in 33.0% of non-infectious and in 28.1% of infectious cases, and was highest in sarcoidosis (50.0%) and CMV anterior uveitis (77.8%). Glaucoma surgery was required in 41.0% of non-infectious and 60.0% of infectious cases. The MD slope was the most negative in anterior uveitis, and IOP fluctuation was weakly significantly negatively correlated with the MD slope. Glaucoma is more common in chronic and anterior uveitis. Sarcoidosis, Vogt-Koyanagi-Harada disease, and CMV anterior uveitis show high comorbidity. Greater IOP fluctuation may correlate with faster visual field deterioration.

To evaluate the demographic, clinical, and laboratory characteristics of pediatric non-infectious uveitis and to identify factors associated with ocular complications and the need for biological therapy. In this retrospective study, 133 pediatric patients with non-infectious uveitis were grouped according to the presence of ocular complications and the need for biological therapy. Logistic regression analysis was performed to identify predictors of ocular complications. Our study included 133 patients with a median follow-up period of 24&#x2009;months. Most cases were anterior (71.4%), bilateral (75.9%), and chronic (75.2%). Ocular complications were observed in 53.4% of patients; the most common were posterior syenchiae. In univariate analysis, younger age at onset (OR 0.88, 95% CI 0.81-0.97), chronic disease course (OR 2.52, 95% CI 1.12-5.68), lower baseline BCVA (OR 1.62 per 0.1 logMAR increase, 95% CI 1.34-1.96), and lower BCVA at the latest visit (OR 1.91 per 0.1 logMAR increase, 95% CI 1.44-2.53) were associated with complications. In multivariate analysis, baseline BCVA remained the only independent predictor of ocular complications (OR 1.58 per 0.1 logMAR increase, 95% CI 1.29-1.94). Patients requiring biological therapy were more frequently female, had earlier disease onset, chronic course, more frequent posterior syenchiae, and higher PLT levels. Low baseline BCVA was the only independent predictor of ocular complications. Younger age at onset and chronic disease course were associated with complications. More frequent monitoring might be considered in patients with lower baseline BCVA, chronic course, female gender, posterior syenchiae and higher baseline PLT levels.

Anterior uveitis (AU) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). This study investigates the shared genetic architecture and pleiotropic loci between AU and IBD. Using large-scale GWAS data from European-ancestry cohorts, we performed LD score regression to assess genetic correlations, two-sample Mendelian randomization for causal inference, and PLACO analysis to identify pleiotropic loci. Multi-trait colocalization integrating 412 gut microbiome features was conducted using HyPrColoc. Functional annotation employed FUMA and ANNOVAR, gene-based analysis used MAGMA, and drug-gene interactions were explored via DrugBank. AU showed significant genetic correlations with IBD (rg&#x2009;=&#x2009;0.44, p&#x2009;=&#x2009;2.0&#x2009;&#xd7;&#x2009;10-4), ulcerative colitis (rg&#x2009;=&#x2009;0.52, p&#x2009;=&#x2009;6.0&#x2009;&#xd7;&#x2009;10-4), and Crohn's disease (rg&#x2009;=&#x2009;0.24, p&#x2009;=&#x2009;0.029). Mendelian randomization supported causal effects of genetically predicted IBD and its subtypes on AU risk. We identified 62 pleiotropic risk loci, including 18 with strong colocalization evidence. Functional and pathway analyses revealed enrichment of these loci in immune and inflammatory pathways, mainly the IL-17/IL-23 axis and NOD2 signaling. Multi-trait colocalization further linked a shared AU-IBD risk locus to the gut microbial MEP pathway. Several pleiotropic genes (e.g. JAK2, STAT3) represent potential drug targets. AU and IBD share pleiotropic genetic loci involved in immune regulatory pathways and gut microbiome-associated metabolic processes, revealing a potential molecular basis for their comorbidity and highlighting actionable therapeutic targets.

To report a rare case of concurrent tuberculous peritonitis (TBP) and ocular tuberculosis presenting as choroidal tuberculoma and exudative retinal detachment in a young male, highlighting the potential for multisystem dissemination and risk of visual impairment when ocular involvement is overlooked. This report describes a 20-year-old male patient who presented with abdominal pain and was confirmed to have TBP through imaging and histopathology, subsequently developing ocular complications during anti-tuberculous therapy. During treatment for TBP, the patient developed choroidal tuberculoma and exudative retinal detachment, demonstrating that ocular tuberculosis can manifest despite appropriate systemic antimicrobial therapy and represents progressive multisystem dissemination. This case underscores the potential for multisystem dissemination of tuberculosis and the complexity of its clinical manifestations, particularly in adolescents and young males. It emphasizes that ocular tuberculosis can coexist with TBP and may be frequently overlooked, potentially resulting in visual impairment, thereby warranting comprehensive evaluation in young patients with extrapulmonary tuberculosis.

To describe the long-term ocular and systemic course of a pediatric patient with Blau syndrome carrying aNOD2p.Arg587Cys mutation, and to report the therapeutic response to infliximab after inadequate disease control with adalimumab. Single-case report of a girl with genetically confirmed Blau syndrome managed at a tertiary referral center for pediatric uveitis in Japan. Clinical findings, multimodal imaging, treatment course, and long-term outcomes were reviewed from infancy through late childhood. Ocular inflammation was assessed by slit-lamp biomicroscopy, fundus examination, fluorescein angiography, and optical coherence tomography. Systemic therapy comprised methotrexate and tumor necrosis factor-alpha (TNF-&#x3b1;) inhibitors. The patient developed recurrent fever and urticaria-like rash at 7months of age, followed by bilateral granulomatous uveitis with optic disc edema at 9months. Genetic testing at 14months identified a heterozygousNOD2p.Arg587Cys mutation, confirming Blau syndrome. Methotrexate combined with adalimumab achieved only partial control: ocular inflammation recurred despite normalization of C-reactive protein and erythrocyte sedimentation rate, and recurrent hypopyon developed even after dose escalation to the standard pediatric maximum. After switching to infliximab at 4years and 6months of age, sustained remission was maintained for more than four years, with stable visual acuity, stable intraocular pressure, and no further ocular or systemic relapses. In this patient, systemic inflammatory markers did not reliably reflect intraocular disease activity, and infliximab achieved durable remission of Blau-associated uveitis refractory to adalimumab. Although limited to a single observation, the long-term outcome supports infliximab as a salvage option in refractory pediatric Blau-associated uveitis and underscores the value of ophthalmologic-rather than serological-monitoring of disease activity.

To characterize posterior segment involvement in subacute sclerosing panencephalitis (SSPE) using clinical and multimodal imaging findings. Retrospective evaluation of three patients with SSPE presenting with posterior segment findings. Ophthalmic examination, fundus photography, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), neurological assessment, and clinical outcomes were reviewed. Three patients (aged 10, 16, and 22&#x2009;years) demonstrated variable posterior segment involvement, including macular chorioretinitis, retinal pigment epithelium (RPE) alterations, macular edema, superficial hemorrhages, vascular dilatation, subretinal membrane formation, serous retinal detachment, and macular scarring. In two cases, ocular findings preceded or contributed to the suspicion of SSPE. One patient initially presented with visual complaints and subtle neuropsychiatric symptoms, leading to a delayed neurological diagnosis confirmed by electroencephalography and cerebrospinal fluid analysis. OCT revealed macular edema, retinal thinning, atrophy, and a characteristic patchy intraretinal degeneration pattern resembling a moth-eaten appearance in affected areas. Partial visual improvement was observed in one patient following treatment with levetiracetam, isoprinosine, and interferon beta-1a, whereas two patients showed neurological deterioration and died within four months and two years, respectively. Posterior segment findings in SSPE are heterogeneous and may precede neurological manifestations. Multimodal imaging, particularly OCT and FFA, provides valuable diagnostic insights. Early recognition of these ocular features may facilitate timely diagnosis and management of SSPE.

Aim: Dry eye disease (DED) is a chronic, multifactorial condition arising through loss of tear film and ocular surface homeostasis. Treatment aims to restore natural tear production and normalize ocular surface homeostasis. Several prescription medications are available in the US that increase tear production in patients with DED. In the absence of head-to-head trials, this study employed a matching-adjusted indirect comparison (MAIC) approach to estimate the comparative tear production efficacy of acoltremon 0.003% and cyclosporine 0.05% for the treatment of DED. Materials & methods: MAICs were conducted for the key outcome of categorized Schirmer test score (STS), where higher values indicate greater tear production. Patient data were available for acoltremon 0.003% (from COMET-2 and COMET-3 trials) and summary level data for cyclosporine 0.05%. Populations were matched on clinically relevant variables including age, race, sex and anesthetized categorized STS. The primary analysis compared mean change from baseline (CFB) categorized STS at day 90. An exploratory analysis investigated earlier onset of tear production (day 14) attributed to acoltremon 0.003% compared with the earliest available data (day 90) for cyclosporine 0.05%. Results: After all adjustments, a greater mean CFB categorized STS was observed for acoltremon 0.003% compared with cyclosporine 0.05% (mean difference [MD]: 1.62 categories, 95% CI: 1.42-1.83, p&#xa0;<&#xa0;0.001) at day 90. The exploratory analysis also demonstrated a greater mean CFB categorized STS for day 14 acoltremon 0.003% compared with day 90 cyclosporine 0.05% (MD: 1.62 categories, 95% CI: 1.42-1.82, p&#xa0;<&#xa0;0.001). Conclusion: Our findings suggest that acoltremon 0.003% may provide a greater increase in tear production relative to cyclosporine 0,05% at day 90, with exploratory findings suggesting similar results at day 14. As this was an unanchored MAIC, results may be influenced by residual confounding from unmeasured differences between trials. A statistical comparison of two prescription eye drops (acoltremon 0.003% and cyclosporine 0.05%) for increasing tear production in patients with eye disease. What is the article about? Dry eye disease (DED) is generally associated with a deficiency in the quantity and/or quality of tears. We compared how well acoltremon 0.003% and cyclosporine 0.05% increase tear production in adults with DED. What was the methodology used? As there are no direct comparison trials between acoltremon 0.003% and cyclosporine 0.05%, we used a matching-adjusted indirect comparison approach using patient-level data for acoltremon 0.003% and published population data for cyclosporine 0.05%. This method reweights individual patient data from the acoltremon 0.003% trials to match published summary cyclosporine 0.05% data. This ensures the two groups are as similar as possible for a fair comparison. A categorized Schirmer test score was used as a measure of tear production, and we considered the average difference in the change from baseline in categorized Schirmer&#x2019;s test result at day 90 for each treatment as the main end point in this analysis. What were the results? Our results suggest that after 90&#xa0;days on the therapies, patients using acoltremon 0.003% had significantly greater tear production than patients using cyclosporine 0.05%, with a mean difference of 1.62 categories for the Schirmer test score. Why is this important? These results support acoltremon 0.003% as a valuable treatment option for the signs and symptoms of DED.

Describe findings of three cases of culture and PCR negative hypertensive anterior uveitis following intravitreal faricimab. This is a case series of three patients undergoing treatment for diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). Data collected included visual acuity, intraocular pressure (IOP), slit lamp examination (SLE), anterior chamber (AC) tap, vitreous tap with culture, and fluorescein angiography (FA). Three patients developed hypertensive uveitis following repeated intravitreal faricimab injections for DME or nAMD. All presented within 2-5&#x2009;weeks of injection with ocular pain and redness. Exam revealed elevated intraocular pressure (22-52&#x2009;mmHg), and keratic precipitates with anterior chamber inflammation. Infectious and inflammatory workups, including aqueous and/or vitreous PCR for HSV, VZV, and CMV, were negative in all cases. Faricimab was discontinued and topical and/or local corticosteroids initiated, with adjunctive IOP-lowering therapy as indicated. Inflammation resolved in all patients within 3&#x2009;months without recurrence after switching intravitreal anti-VEGF agents. Final visual acuity ranged from 20/25 to count fingers, limited by glaucomatous optic neuropathy in one case. Hypertensive anterior uveitis with diffuse KPs is a potential rare complication of intravitreal faricimab and must be considered in patients presenting with new ocular inflammation or IOP elevation while undergoing treatment with faricimab. The intraocular inflammation appears to respond well to discontinuation of faricimab and treatment with local corticosteroids.