Search Results (450)

Background: Multiple evanescent white dot syndrome (MEWDS) is usually acute and self-limited, whereas multifocal choroiditis (MFC)/punctate inner choroidopathy (PIC) is relapsing; overlap can obscure early diagnosis and requires longitudinal multimodal imaging. Methods: We report a 4-year follow-up of a 31-year-old woman with fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT), plus a systemic/neurologic/rheumatologic work-up. Treatment included intravenous methylprednisolone for presumed optic neuritis, followed by topical, periocular, intravitreal, and systemic corticosteroids, later escalated to adalimumab and an intravitreal dexamethasone implant. Because foveal granularity could not be documented, baseline was termed “MEWDS-like”. Diagnostic labelling was benchmarked against Standardization of Uveitis Nomenclature (SUN) criteria, and choroidal neovascularization (CNV) was assessed at each relapse by OCT and FA. Results: The right eye initially showed a MEWDS-like pattern with wreath-like FA lesions and disc leakage, hyperautofluorescent FAF lesions, focal ellipsoid zone disruption on SD-OCT, and multifocal ICGA hypofluorescent spots. A relapse at 6 months with peripapillary inflammatory foci and recurrent cystoid macular edema supported reclassification to a unilateral MFC/PIC-spectrum phenotype. At 2 years, the fellow eye developed mild vitritis, peripapillary hyperautofluorescence, peripapillary/arcade leakage on FA, delayed peripapillary filling on ICGA, and cystoid macular edema, establishing sequential bilateral MFC; no CNV developed and anti-vascular endothelial growth factor (anti-VEGF) therapy was not required. Complications included steroid-induced ocular hypertension and cataract surgery. Conclusions: The purpose of this report is to highlight longitudinal imaging “red flags” that supported reclassification from a MEWDS-like phenotype to a sequential bilateral MFC/PIC-spectrum disease. Full article

Lysine lactylation represents a novel post-translational modification (PTM) involved in cellular functions including glycolysis and macrophage polarisation. It differs in form and mechanism from other PTMs such as acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation. As a recently discovered modification, lactylation has been implicated in the progression of multiple diseases. Recent studies further indicate lactylation’s association with multiple ocular pathologies. This review systematically summarises and discusses lactylation’s involvement in prevalent eye diseases, including myopia, retinopathy, ocular melanoma, uveitis, and macular degeneration. We further collate emerging data suggesting lactylation signalling pathways may represent potential therapeutic targets for ocular pathologies. This review aims to provide a comprehensive overview for holistic intervention strategies and multidimensional assessment across various ocular conditions, while offering valuable insights for future research and development from a lactylation perspective. Full article

Background: Behçet’s disease (BD) is a systemic inflammatory disorder marked by recurrent mucocutaneous and ocular manifestations, predominantly affecting populations along the historic Silk Road. Genetic susceptibility, especially involving HLA-B*51, is well established. Spondyloarthritis (SpA) shares immunogenetic and clinical overlaps with BD, notably through associations with HLA class I alleles, particularly HLA-B*27. However, extended HLA-B allele profiling in these conditions remains limited. This study aimed to investigate the extended distribution of HLA-B alleles in patients presenting with clinical features suggestive of BD or SpA and to compare their clinical and laboratory profiles. Methods: In a prospective observational study at a Bulgarian rheumatology center, 120 patients with suspected BD or SpA were enrolled between January 2023 and June 2025. Diagnoses were confirmed using International Criteria for Behçet’s Disease (ICBD) and ASAS criteria for SpA. Comprehensive clinical evaluations, laboratory assessments including HLA-B typing by Sanger sequencing, and inflammatory markers were collected and analyzed. Results: Of the cohort, 15 patients (12.5%) were diagnosed with BD and 30 (25%) with SpA. HLA-B*51 was predominantly associated with BD, while HLA-B*27 and its heterozygous combinations were prevalent in SpA patients. Suspected BD patients exhibited significantly higher levels of inflammatory markers (CRP, ESR) and characteristic clinical features such as oral/genital ulcers and uveitis compared to non-BD patients. Suspected SpA patients showed longer disease duration, increased NSAID use and higher prevalence of enthesitis, psoriasis and peripheral arthritis compared to non-SpA patients. Conclusions: This study confirms the strong associations of HLA-B*51 with Behçet’s disease and HLA-B*27 with spondyloarthritis while revealing additional heterozygous and less common alleles that suggest a broader genetic influence. These findings highlight the genetic diversity and clinical heterogeneity of BD and SpA, supporting the use of extended HLA typing to improve the diagnosis and understanding of these diseases. Full article

Syphilis is a re-emerging sexually transmitted infection with rising incidence worldwide, often associated with HIV infection. Ocular syphilis represents a severe manifestation that can occur at any disease stage and may result in permanent vision loss if not promptly diagnosed and treated. We conducted a retrospective comparative cohort study of 22 patients with ocular syphilis managed at Istanbul University, Istanbul Faculty of Medicine, between 2019 and 2025. Twelve patients (54.5%) were people living with HIV (PLWH). The majority were male (81.8%), with a mean age of 45.2 years. Visual loss was observed in more than half of the patients and occurred significantly more frequently in PLWH than in HIV-negative individuals (100% vs. 70%; p = 0.046). Vitritis was also significantly more frequent among PLWH (91.7% vs. 40%; p = 0.02), indicating more severe intraocular inflammation. All six cases of neurosyphilis were confined to PLWH (50% vs. 0%; p = 0.004). The most common ocular manifestations were uveitis (90.9%), predominantly panuveitis and posterior uveitis. All patients received intravenous penicillin G or ceftriaxone, and systemic corticosteroids were administered in half of the cases. Clinical improvement was observed in all patients. Our findings highlight that ocular syphilis in PLWH is associated with more severe inflammation and higher neurosyphilis risk, underscoring the importance of routine cerebrospinal fluid examination and neurosyphilis-based treatment strategies in this group. Full article

Background: Inflammatory bowel disease (IBD) is associated with numerous extraintestinal manifestations and systemic comorbidities; however, the certainty of prevalence estimates across multiple organ systems has not been systematically evaluated. Objective: To synthesize evidence from systematic reviews on the prevalence of comorbidities in patients with inflammatory bowel disease (IBD) and to assess the certainty of estimates through an umbrella review. Methods: In this umbrella review, we included systematic reviews reporting the prevalence of comorbidities in adults with IBD and their confidence intervals. Methodological quality was assessed using AMSTAR-2 and ROBIS, while statistical heterogeneity and certainty of evidence were evaluated using GRADE adapted for prevalence studies. Results: Eighteen systematic reviews published between January 2014 and September 2025 were included. The highest prevalences were sexual dysfunction 50.6% (95% CI 40.8–60.5), fecal incontinence in Crohn’s disease 34.8% (27.9–41.9), non-alcoholic fatty liver disease 32% (24–40), anemia 24% (18–31), and ≥1 extraintestinal manifestation 24% (19–31). Only four comorbidities achieved moderate certainty: primary sclerosing cholangitis 2.16% (1.76–2.60), uveitis 2.38% (1.60–3.17), hepatitis B 3.3% (2.5–4.0), and hepatitis C 1.8% (1.2–2.4). Prevalence rates varied significantly by IBD subtype, geographic region, and diagnostic method. Heterogeneity was consistently high (I² > 90%), and certainty was predominantly low or very low. Conclusions: Comorbidities in IBD are frequent, with prevalences ranging from 1.8% to 50.6%, highlighting the importance of comorbidity awareness in clinical practice. However, the certainty of evidence is predominantly low or very low due to extreme methodological heterogeneity. These findings underscore the urgent need for studies with standardized diagnostic methods and robust statistical approaches to strengthen the evidence base and establish evidence-based surveillance protocols. Full article

Background: Psoriasis is a chronic systemic inflammatory disease with established extra-cutaneous manifestations. While the association between uveitis and spondyloarthritis (SpA)-related disorders is well recognized, the incident risk of uveitis among broader psoriasis populations remains inadequately defined due to methodological limitations and inconsistent findings across previous studies. We aimed to estimate the incidence of uveitis in a large, nationwide population-based cohort and identify specific clinical and treatment-related predictors of ocular inflammation. Methods: This retrospective cohort study utilised electronic health records from Clalit Health Services, Israel’s largest health maintenance organization (2002–2024). We identified 157,360 patients with dermatologist-confirmed psoriasis and 156,927 age- and sex-matched controls. The primary outcome was incident uveitis, with risk estimated using Cox proportional hazards models. Within the psoriasis cohort, multivariable logistic regression was employed to identify predictors of uveitis, ensuring appropriate temporal sequencing between psoriasis treatment exposure and outcome. Results: Over a median follow-up of 12.6 years, psoriasis was associated with a significantly higher risk of incident uveitis (adjusted Hazard Ratio [aHR] 1.80; 95% CI, 1.50–2.15). Stratified analysis revealed a graded risk pattern: mild psoriasis showed no increased risk (aHR 1.01; 95% CI, 0.91–1.13), whereas severe disease (aHR 1.59; 95% CI, 1.25–2.03) and concomitant SpA (aHR 2.21; 95% CI, 1.87–2.61) demonstrated markedly elevated risks. Within the psoriasis cohort, independent predictors included SpA, diabetes mellitus, systemic lupus erythematosus, and sarcoidosis. Exposure to biologics, particularly etanercept (OR 3.37; 95% CI, 2.42–4.54), was associated with higher odds of uveitis, potentially reflecting higher disease severity. Conclusions: Incident uveitis risk in psoriasis is primarily driven by the magnitude of systemic inflammatory burden, with the highest risk observed in severe disease and those with concomitant SpA. Clinicians should maintain heightened vigilance for ocular symptoms in these high-risk subgroups to ensure timely intervention. Full article

Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing strategies. As the use of immunotherapy expands, recognizing toxicity from recurrence and optimizing response-adapted approaches are essential to balance cure with quality of survival. Case Presentation: A 38-year-old pregnant woman with a distant history of uveitis and psoriasis was discovered to have pregnancy-associated TNBC. Postnatally, she was treated with neoadjuvant chemotherapy and pembrolizumab, followed by wire-guided left breast wide local excision and sentinel lymph node biopsy of the left axilla. After surgery, residual cancer was noted. She continued adjuvant pembrolizumab and adjuvant radiotherapy 40.05 Gy/15 fr to the breast and nodes, followed by a 13.35 Gy/5 fr boost to the tumour bed (breast). Despite a persistent residual tumour, pembrolizumab was continued as per protocol in a response-agnostic manner. At the end of one year of adjuvant pembrolizumab, she developed progressive numbness and weakness in the ipsilateral arm, initially raising suspicion for local recurrence. Comprehensive MRI and PET-CT imaging did not identify recurrent tumour or new metastatic disease. Electromyography confirmed a lower-trunk brachial plexopathy without a structural cause. An immune-mediated process was diagnosed by a process of elimination. Despite treatment with 1st-line high-dose corticosteroids and 2nd-line intravenous immunoglobulin (IVIG), improvement was limited. Therapeutic plasmapheresis led to marked functional recovery and symptom resolution 20 months later. Discussion: Four main challenges are identified: (1) the diagnostic difficulty in identifying local recurrence or radiation injury from immune-related neuropathy; (2) the emerging therapeutic role of plasmapheresis in steroid-refractory irAEs; (3) the possible inconsistencies between rare toxicities observed in clinical trials vs. clinical practice; and (4) the limitations in response in adjuvant therapy, particularly in patients with coexisting AI conditions. Conclusions: Early recognition and accurate distinction from tumour recurrence, as well as support for plasmapheresis as a potential option in steroid-refractory presentations, have been shown to improve patient survival and symptom reduction. With increasing use of immunotherapy, real-world toxicity data, predictive biomarkers, and personalized treatment strategies are urgently needed to balance cure with long-term functional outcomes. Full article

Canine visceral leishmaniasis (CVL), caused by Leishmania infantum, is a multisystemic disease in which ocular involvement is frequent but often underestimated. This study aimed to comprehensively evaluate the clinical, ophthalmological, parasitological, hematological, biochemical, and histopathological alterations in dogs naturally infected with L. infantum from an endemic area of northeastern Brazil, with special emphasis on the relationship between ocular manifestations and systemic disease. Twenty-five symptomatic dogs were evaluated through clinical and ophthalmological examinations, parasitological culture, PCR, laboratory analyses, and histopathology of ocular and periocular tissues. Ocular alterations were observed in 80% of the animals, predominantly bilateral and frequently associated with multiple concurrent lesions, including ocular discharge, conjunctivitis, blepharitis, uveitis, and corneal opacity. Functional ophthalmological tests revealed keratoconjunctivitis sicca and corneal ulcers in a substantial proportion of dogs. Hematological abnormalities were highly prevalent, particularly anemia and thrombocytopenia. Comparative analysis demonstrated that dogs with ocular involvement exhibited significantly higher leukocyte counts and segmented neutrophils, as well as increased AST levels, indicating an enhanced systemic inflammatory response. Histopathological examination revealed intense plasmacytic inflammatory infiltrates and the presence of amastigote forms in ocular and periocular tissues, indicating that both immune-mediated and parasite-driven mechanisms could be involved in disease pathogenesis. Collectively, these findings underscore ocular involvement as a clinically relevant manifestation of CVL and reinforce the importance of routine ophthalmological evaluation in clinical management. Full article

In carbon monoxide (CO) therapy, CO is administered at low concentrations as a controlled solution; this approach enables the drug to achieve its cytoprotective properties, including anti-inflammatory, anti-apoptotic, and vasodilatory effects. CO therapy, initially reported to benefit cardiovascular and pulmonary conditions, is now used to treat ocular diseases in preclinical models. Carbon monoxide, a compound most famously known for its deleterious effects, is receiving more attention as a potential therapeutic candidate in ocular medicine. In a few studies, controlled low-dose CO therapy has shown anti-inflammatory and anti-apoptotic effects in various models of retinal disease (such as retinal ischemia-reperfusion injury, optic nerve crush, ocular hypertension, and autoimmune uveitis). We have summarized the clinical and preclinical findings, along with the potential therapeutic value of CO, in this review. In this context, the current and emerging CO delivery methods are also described, with a focus on exploring their safety, efficacy, and applicability in retinal disorders. Although a strong preclinical paradigm exists, clinical translation is limited at best. While some trials indicate acceptable safety levels for inhaled CO or CORM-based interventions, these results have not been robust or reproducible. Bridging this efficacy gap will rely on enhanced delivery strategies, stringent PK/PD-informed dosing, and mechanism-specific endpoint-based trials. Full article

Herpes simplex virus type 1 (HSV-1) initiates infection through sequential interactions with host receptors, yet the early transcriptional responses driving HSV-mediated iritis remain poorly understood. Given the clinical burden of HSV-induced anterior uveitis and the lack of targeted therapies, we sought to define the initial host response to infection. We performed temporal transcriptomic profiling of primary human iris stromal (HIS) cells at 1, 3, and 6 h post-infection. HSV-1 triggered rapid and extensive gene expression changes, with early activation of IL-17, TNFα, MAPK, and NF-κB signaling pathways, all associated with inflammation and stress responses. At later time points, pathways related to epithelial–mesenchymal transition and the G2/M checkpoint were upregulated, alongside sustained inflammatory signaling, suggesting a balance between stromal integrity and stress adaptation. Imaging studies, together with transcriptomic data, revealed modulation of HS3ST enzymes and a corresponding loss of heparan sulfate and syndecans. These transcriptional dynamics mirror those observed in HSV-1-induced keratitis, indicating a conserved ocular response across cell types. By mapping these early events, this study identifies potential molecular targets for therapies aimed at mitigating inflammation during HSV-induced iritis. Full article

Experimental autoimmune uveitis (EAU) in rats is a pivotal model for understanding the immunological mechanisms of human uveitis and developing therapies. In humans, optical coherence tomography (OCT) allows for the in vivo detection of characteristic findings in active uveitis, as well as sequelae of inflammation. The objective of this study was to correlate OCT findings in patients with uveitis with retinal histologies from two rat models of EAU caused by T cells with different autoantigen specificities and well-known underlying immunological pathomechanisms. Patients with various noninfectious uveitis subtypes underwent imaging using an ultra-widefield swept source or conventional OCT. Histological cryosections from rat eyes with experimental autoimmune uveitis were stained for T cell and/or macrophage markers. Typical human OCT findings were reproduced in the experimental animal model. Hyperreflective signals observed on OCT corresponded to lymphocyte infiltration in histological sections. This infiltration was typically found as vasculitis in the perivascular regions and snowballs in the posterior hyaloid. There was lymphocyte and macrophage infiltration of the retina through the retinal vessels and the retinal pigment epithelium. Comparing in vivo OCT imaging of human uveitis with corresponding histologies from rat models improves our understanding of the type of inflammation, extent of tissue destruction, and immunopathogenesis. Full article

Ophthalmic diseases, including inherited retinal dystrophies, age-related macular degeneration (AMD), and glaucomatous neuropathies, are often driven by the expression of pathogenic proteins or dysfunctional non-coding RNAs that are currently considered ‘undruggable’ with conventional small-molecule therapeutics. The emerging strategy of Ribonuclease-Targeting Chimeras (RIBOTACs) offers a revolutionary approach to address this therapeutic gap. RIBOTACs are heterobifunctional small molecules designed to bind a specific target RNA with one moiety and recruit a latent endogenous ribonuclease, such as RNase L, with the other, thereby catalyzing the RNA’s degradation. This targeted degradation can potentially halt the production of mutant proteins, eliminate toxic gain-of-function RNAs, or modulate key regulatory pathways involved in angiogenesis, inflammation, and apoptosis—core processes in many blinding diseases. This review explores the immense potential of applying RIBOTAC technology to ophthalmology, discussing prospective targets such as mutant alleles in retinitis pigmentosa, VEGF transcripts in neovascular AMD, and inflammatory mediators in uveitis. We will also address the unique challenges and opportunities for RIBOTAC development in the eye, including delivery strategies to overcome ocular barriers, the need for high specificity to avoid off-target RNA degradation, and the optimization of pharmacokinetic properties for intraocular administration. With continued innovation, RIBOTACs are poised to evolve into a robust therapeutic platform, expanding the druggable genome and enabling precise, durable treatments for a range of currently intractable ophthalmic conditions. Full article

Varicella-Zoster Virus (VZV) is one of the most important pathogens in ophthalmology. Reactivation may involve the adnexa (blepharoconjunctivitis, pseudomembranous conjunctivitis), cornea (dendritic keratitis, nummular and necrotizing stromal keratitis, disciform endotheliitis, neurotrophic ulcers, mucous-plaque keratitis) and sclera (episcleritis, anterior scleritis). Uveal inflammation ranges from anterior uveitis—with iris atrophy, trabeculitis-induced glaucoma and complicated cataract—to posterior necrotizing syndromes: acute retinal necrosis in immunocompetent hosts and progressive outer retinal necrosis in immunosuppressed patients, often complicated by occlusive vasculitis, macular edema, retinal detachment and phthisis. Optic nerve and cranial nerve involvement (optic neuritis, neuroretinitis, III/IV/VI palsies) and orbital inflammation may occur even without cutaneous signs (“zoster sine herpete”), making PCR-based intraocular diagnostics essential. Management relies on early, high-dose antivirals (acyclovir or valacyclovir), judicious corticosteroids and timely surgical intervention when required. Universal childhood varicella vaccination and recombinant zoster vaccination in adults ≥50 years have reduced VZV incidence and ocular complications in settings with high vaccine coverage, though rare post-vaccine keratitis or uveitis underscore the need for ongoing vigilance. In this review, we synthesize current knowledge on varicella-zoster virus ocular disease, with a focus on host–pathogen interactions that drive both injury and defense. Full article

Background/Objectives: To evaluate the incidence, characteristics, and clinical outcomes of intraocular inflammation (IOI) associated with intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Web of Science, Scopus, Embase, and CENTRAL databases was performed from their inception to February 2025. Using the random-effects model, weighted proportions, standardized mean differences, and weighted log odds ratios (OR) were pooled and calculated. A two-tailed p-value of <0.05 was considered statistically significant. The χ² (z) test and the Higgins I² test were used to assess studies heterogeneity. Results: We conducted a systematic review and meta-analysis of 24 studies (4761 patients; 5652 eyes). The most common diagnoses were nAMD (n = 4782, 94.6%) and DME (n = 845, 37.1%). The pooled proportion for IOI incidence in eyes receiving IVF was 3.0% (95% CI: 1.0–6.0). The odds of developing IOI did not differ significantly between the DME and nAMD groups (OR: 1.13, p = 0.78). Unspecified IOI was the most common sign (n = 210, 2.9% [95% CI: 1.2–7.3]), followed by anterior uveitis (n = 80, 1.9% [95% CI: 0.1–34.8]), vitritis (n = 63, 2.9% [95% CI: 0.2–32.1]), retinal hemorrhage (n = 27, 0.7% [95% CI: 0.0–15.3]), and endophthalmitis (n = 8, 0.5% [95% CI: 0.3–1.1]). Conclusions: While IVF demonstrates therapeutic efficacy, our findings highlight a clinically relevant risk of IOI. We, therefore, recommend vigilant clinical monitoring in patients receiving this therapy. Full article

Members of the microsporidial genus Encephalitozoon have the capacity to infect both mammals and birds, and E. cuniculi is most commonly found in rabbits. With a seroprevalence ranging up to 85%, E. cuniculi can be a problem in pet rabbits as well as in food production and laboratory animal science. While most infections are likely subclinical, there are three main clinical presentations: neurological, renal, and ocular. Typical clinical signs including vestibular disease and phacoclastic uveitis may develop with initial or relapsing infection, while renal infection is usually progressive and associated with non-specific clinical signs. High-sensitivity/specificity ante mortem diagnostic options are lacking, and serological testing most often provides adjunct rather than definitive information such that physical examination and other diagnostics are used more so for ruling out other differentials and comorbidities, rather than confirming infection. In the veterinary community, treatment regimens are variable given the lack of thorough studies and a consensus. The aim of this document is to present the available literature to give a concise review of this organism and its infection of rabbits as well as to propose guidelines and protocols for diagnostics and treatment regimens. In addition, the current challenges and recommendations for further studies are discussed. Full article