Koju Kamoi

Antibodies in ocular disease have heterogeneous biological meanings: they may act as direct pathogenic effectors, systemic diagnostic biomarkers, indicators of B-cell clonality, or therapeutic agents. This distinction is particularly important in the eye, where immune privilege and the blood–ocular barrier restrict tissue access, whereas inflammation may permit entry of immunoglobulins, complement, and immune cells or support local humoral responses. This narrative review integrates antibody and B-cell biology across autoimmune and paraneoplastic retinopathies, aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, ocular mucous membrane pemphigoid, ocular myasthenia gravis, thyroid eye disease, systemic autoimmune and fibroinflammatory disorders with ocular involvement, and B-cell malignancies including vitreoretinal and ocular adnexal lymphoma. We distinguish the evidence for direct antibody pathogenicity from disease association and emphasize that a positive result is interpretable only in relation to the ocular phenotype, assay platform, titer, specimen compartment, and orthogonal confirmation. Serum testing, ocular-fluid analysis, electrophysiology, multimodal imaging, cytology, histopathology, immunophenotyping, immunoglobulin clonality, and molecular testing have complementary roles. Therapeutic strategies include B-cell or B-lineage depletion, complement inhibition, cytokine- or receptor-directed monoclonal antibodies, insulin-like growth factor-1 receptor blockade, and emerging FcRn- or plasma-cell-directed approaches; however, regulatory status and ocular-specific evidence vary substantially among diseases. A mechanistically stratified framework may reduce overdiagnosis, improve recognition of malignant masquerade syndromes, and support more precise selection of targeted therapy.

Uveitis comprises a heterogeneous group of intraocular inflammatory diseases that differ in anatomical location, etiology, clinical course, and immune mechanisms. Despite this diversity, evidence derived predominantly from experimental autoimmune uveitis (EAU) suggests that oxidative stress may act as a context-dependent amplifier linking immune activation, ocular barrier dysfunction, and tissue injury. Excess reactive oxygen species (ROS) disrupt redox homeostasis and activate redox-sensitive inflammatory signaling, thereby amplifying cytokine production, mitochondrial dysfunction, leukocyte recruitment, and retinal damage. This review summarizes current evidence on oxidative stress in uveitis, focusing on major ROS-generating systems, NF-κB-driven inflammation, Nrf2/HO-1-mediated antioxidant responses, MAPK and PI3K-Akt signaling, and immune–metabolic pathways involved in autoimmune ocular inflammation. Cell-specific responses in retinal and immune cells further illustrate how redox imbalance may contribute to local tissue injury and immune-mediated disease progression. The role of oxidative stress in blood–ocular barrier dysfunction, particularly blood–retinal barrier disruption during posterior segment inflammation, is also discussed. Overall, preclinical studies support an active role for oxidative stress in inflammatory amplification and ocular tissue injury, whereas evidence from patients with defined uveitic entities remains limited, heterogeneous, and largely associative. Redox-directed treatments should therefore currently be regarded as investigational adjunctive strategies rather than established therapies for uveitis.

Purpose: Noninfectious uveitic macular edema (UME) is a major cause of visual impairment and remains challenging in refractory cases. Although adalimumab (ADA) is an effective biologic therapy, its delayed onset may limit early disease control, suggesting a potential role for bridging strategies such as local corticosteroid injection. This study compared ADA monotherapy with ADA combined with sub-Tenon’s triamcinolone acetonide (STTA) bridging therapy in refractory noninfectious UME. Methods: In this retrospective longitudinal cohort study, 30 patients (44 eyes) with refractory noninfectious UME treated with ADA (2015–2025) were included. Patients received either ADA monotherapy or ADA with STTA bridging therapy. Outcomes included time to improvement (≥ 20% reduction in central subfield thickness (CST) with reduced cystoid spaces), relapse after resolution, longitudinal CST changes, best-corrected visual acuity (BCVA, LogMAR), and intraocular pressure (IOP). Time-to-event analyses were performed using Cox regression, and Longitudinal data using generalized estimating equation models adjusted for baseline covariates. Results: Bridging therapy was associated with a shorter time to improvement (log-rank p = 0.008; HR 2.850, 95% CI 1.402–5.794; p = 0.004). Adjusted analyses showed greater visual improvement in the bridging group at 12 months (difference 0.307 LogMAR; p < 0.001) and at 15, 24, and 36 months ( p < 0.05). Greater CST reductions were observed at 3, 18, 21, and 36 months ( p < 0.05). Relapse risk did not differ significantly (HR 0.711, 95% CI 0.155–3.272; p = 0.662). IOP changes were generally comparable. Conclusion: ADA combined with STTA bridging therapy was associated with earlier anatomical improvement and additional visual benefits compared with ADA monotherapy, without increased relapse risk.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by restoring anti-tumor immunity, but immune activation can disrupt ocular immune homeostasis and induce ophthalmic immune-related adverse events (OirAEs). Although uncommon, OirAEs may involve nearly all ocular compartments and can cause irreversible visual impairment or interruption of effective anticancer therapy. The 2025 international consensus criteria now provide a standardized framework for defining and classifying OirAEs. This review integrates current evidence on ICI-associated ocular toxicity, with emphasis on tissue-specific immune mechanisms and their clinical implications. Blockade of the PD-1/PD-L1 and CTLA-4 pathways may impair ocular immune privilege, expand autoreactive T-cell subsets, alter cytokine and chemokine networks, and amplify autoantibody-mediated retinal injury. These processes provide a plausible framework for understanding diverse phenotypes, including uveitis, ocular surface disease, optic neuritis, orbital inflammation, ocular myopathy, and retinopathy. We also outline a mechanism-informed management approach that balances visual preservation with maintenance of systemic anti-tumor immunity. Local corticosteroid therapy, cautious systemic immunosuppression, and selected steroid-sparing biologics should be individualized according to severity, anatomical involvement, and the oncologic context. Together, these insights support a consensus-based and mechanism-informed framework for recognizing and managing OirAEs while preserving systemic anti-tumor immunity.

Uveitis is a heterogeneous group of intraocular inflammatory diseases and an important cause of visual impairment worldwide. Although current treatments mainly target inflammation, many patients develop chronic or recurrent disease, suggesting that inflammation control alone may not fully restore intraocular homeostasis. Increasing evidence highlights the blood–ocular barrier (BOB), including the blood–retinal barrier and blood–aqueous barrier, as a key regulator of the intraocular microenvironment. This review aims to summarize the bidirectional interaction between intraocular inflammation and blood–ocular barrier dysfunction in uveitis, and to highlight the clinical significance of barrier dysfunction in disease monitoring and management. In addition, this review discusses the potential value of incorporating barrier assessment into dynamic disease evaluation and relapse-aware management strategies. Recent studies suggest that inflammation and BOB dysfunction are bidirectionally linked. Inflammatory mediators disrupt barrier integrity, while barrier breakdown facilitates immune cell infiltration and further amplifies inflammation, forming a self-reinforcing cycle that may drive disease persistence. Importantly, BOB dysfunction also has clinical implications. Findings such as aqueous flare, macular edema on optical coherence tomography, and vascular leakage on fluorescein angiography reflect barrier status and can serve as dynamic indicators for disease monitoring. Persistent abnormalities despite reduced inflammatory cell activity may indicate incomplete barrier recovery or subclinical inflammation, helping to explain discordant clinical findings and the relapse-prone nature of uveitis. Rather than viewing BOB dysfunction solely as a pathological consequence of inflammation, this review highlights the potential clinical value in disease assessment and management. Barrier-related findings may provide additional information beyond conventional inflammatory evaluation, particularly in cases where inflammatory cell activity appears controlled, but underlying barrier alteration persists. Incorporating barrier assessment into monitoring may help interpret discordant clinical findings, improve evaluation of disease control, and support a more relapse-aware management strategy in uveitis. In addition, therapeutic approaches aimed at restoring barrier integrity may provide a more comprehensive strategy for achieving sustained remission and reducing recurrence risk.

Background: Hematologic malignancies (HMs), including leukemia and lymphoma, are systemic diseases that may cause a wide range of ocular manifestations. Methods: We searched PubMed/MEDLINE (2015-2026) and identified articles with an emphasis on clinically relevant studies and recent developments. Results: Clinically, ocular involvement presents with diverse manifestations, including retinal hemorrhage, vitreoretinal lymphoma, choroidal infiltration, orbital masses, treatment-related ocular toxicities, graft-versus-host disease, and secondary infectious complications. These findings may mimic other ocular diseases and consequently lead to delayed diagnosis. In some cases, ocular manifestations may represent the initial presentation of hematologic malignancies or indicate disease recurrence. Diagnostic evaluation relies on comprehensive ophthalmic examination, imaging, and laboratory analysis. Management strategies include systemic treatment of the underlying malignancy, local ocular therapy, and targeted treatment of infectious or treatment-related complications. Conclusions: Ocular manifestations of hematologic malignancies have significant diagnostic and prognostic implications. Early recognition, multidisciplinary collaboration, and comprehensive ophthalmic assessment are essential for timely diagnosis and optimal management. Improved awareness of disease-related, treatment-related, and infection-related ocular manifestations may facilitate earlier intervention and contribute to better visual and systemic outcomes.

At present, the clinical management of ocular inflammatory diseases predominantly relies on chemically synthesized therapeutic agents. Although these therapies demonstrate established efficacy, their long-term use is associated with substantial economic burden. In addition, they may cause ocular side effects and systemic adverse reactions involving the cardiovascular, hepatic, and renal systems. In contrast, natural products have attracted increasing attention in recent years because many are accessible, relatively cost-effective, and potentially well tolerated. Studies indicate that various natural products exert anti-inflammatory and immunomodulatory effects by inhibiting inflammatory signaling pathways such as NF-κB and MAPK, regulating immune cell function and alleviating oxidative stress responses. These multifunctional properties support their potential therapeutic value in various inflammatory diseases. Notably, several natural products have shown potential benefits in clinical trials; however, their investigation and application in ocular diseases remain relatively limited. In this review, we focus on uveitis and dry eye disease (DED) as representative ocular disease models and systematically summarize the current research progress on four natural products—Paeonia lactiflora extracts, resveratrol and its derivatives, curcumin, and boswellic acids in experimental studies of ocular diseases. We particularly focus on their effects in alleviating ocular surface inflammation and intraocular inflammatory responses through their immunomodulatory mechanisms. This review aims to provide a mechanistic framework for understanding the potential role of natural products as complementary or alternative strategies to current therapeutic approaches, while informing the development of novel therapeutics and future research directions in ocular diseases.

Cytomegalovirus (CMV) infection of the anterior segment is increasingly recognized as an important cause of corneal endotheliitis and secondary glaucoma, even in immunocompetent individuals. CMV corneal endotheliitis typically presents with coin-shaped or linear keratic precipitates (KPs), corneal edema, mild anterior chamber inflammation, and recurrent intraocular pressure (IOP) elevation; persistent or episodic ocular hypertension may progress to glaucomatous optic neuropathy if inadequately treated. Definitive diagnosis relies on aqueous humor polymerase chain reaction (PCR) testing for CMV DNA, supported by adjunctive imaging including specular microscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). Management requires a comprehensive strategy integrating antiviral therapy, anti-inflammatory treatment, and appropriate IOP control. Topical or systemic ganciclovir remains the cornerstone, while refractory disease may necessitate surgical intervention. Older age and male sex, host immune status, prolonged or recurrent CMV infection, and pre-existing ocular conditions are major risk factors for progression and poor outcomes. The pathogenesis of secondary glaucoma is thought to involve both direct viral cytopathic effects and inflammation-mediated damage to the trabecular meshwork (TM), resulting in impaired aqueous outflow. Therefore, early recognition, accurate diagnosis, and effective treatment are essential to prevent corneal decompensation and permanent vision loss.