Molecular Insights into Eyelid Skin Inflammation: Autoimmune Mechanisms, Clinical Manifestations, and Emerging Therapies

1. Introduction

The eyelid represents a unique anatomical and immunological structure that not only protects the ocular surface but also contributes to the homeostasis of the anterior segment of the eye. Unlike other cutaneous sites, eyelid skin is exceptionally thin, richly vascularized, and continuously exposed to mechanical stress from blinking as well as environmental insults such as ultraviolet radiation, allergens, microorganisms, and airborne pollutants. This distinctive microenvironment renders the eyelid particularly susceptible to localized dermatological disorders and systemic autoimmune diseases with periocular involvement [1].

A wide range of inflammatory and autoimmune conditions affect the eyelid and its adnexal structures, often serving as early clinical markers of systemic disease. Notable examples include ocular cicatricial pemphigoid (OCP), pemphigus vulgaris, bullous pemphigoid, thyroid-associated orbitopathy (TAO), and lupus erythematosus. Beyond cosmetic disfigurement, chronic eyelid inflammation may lead to malpositions, trichiasis, and secondary ocular surface damage, ultimately resulting in vision-threatening complications [2,3].

On a molecular level, the immunopathogenesis of eyelid inflammation reflects complex interactions among epithelial barrier disruption, autoreactive lymphocytes, autoantibody-mediated complement activation, and cytokine-driven inflammatory cascades. Dysregulated Th1, Th2, and Th17 pathways, combined with impaired regulatory T cell activity, underlie many autoimmune eyelid diseases. Elevated levels of pro-inflammatory mediators—including interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ)—have been identified in both tissue biopsies and tear fluid. These cytokines orchestrate chronic tissue remodeling, fibrosis, and glandular dysfunction, including meibomian gland dropout and lacrimal gland infiltration, thereby exacerbating ocular surface instability [4].

The periocular microbiome adds another dimension to this pathophysiology. Commensal organisms such as Demodex mites and Corynebacterium species can trigger or perpetuate inflammation through antigen presentation and innate immune activation. The interplay between microbial dysbiosis and host immunity provides new insights into chronic eyelid conditions such as blepharitis, as well as their overlap with systemic autoimmunity [5].

Clinically, eyelid inflammation may precede or parallel systemic autoimmune disease. In OCP, autoantibodies targeting basement membrane zone components (e.g., BP180, laminin-332) drive conjunctival fibrosis and cicatricial eyelid changes. In TAO, orbital and periorbital fibroblast activation, adipogenesis, and inflammatory remodeling result in eyelid retraction and edema. Likewise, systemic lupus erythematosus and Sjögren’s syndrome frequently manifest periocular involvement ranging from cutaneous rashes to chronic meibomian gland dysfunction. Recognizing these early signs is crucial, as untreated periocular inflammation often heralds progressive ocular morbidity [6,7,8].

Therapeutic strategies for autoimmune eyelid inflammation are rapidly evolving. Traditional immunosuppressive approaches—including systemic corticosteroids and antimetabolites—remain standard but are limited by adverse effects. Advances in biologic agents, such as B-cell–depleting therapies (rituximab), TNF-α inhibitors, and monoclonal antibodies targeting IL-17 and IL-23, have significantly expanded the therapeutic landscape. In addition, innovative diagnostic modalities—including tear proteomics and molecular imaging—offer new opportunities for personalized medicine [9,10].

Taken together, the increasing recognition of eyelid involvement in autoimmune diseases underscores the need for a comprehensive review that integrates molecular mechanisms, clinical manifestations, and therapeutic advances. This article is a narrative literature review, synthesizing current molecular and clinical evidence across ophthalmology, dermatology, and immunology, with particular emphasis on autoimmune mechanisms underlying eyelid skin inflammation. By highlighting the eyelid as a model structure for studying the skin–immune–ocular interface, such an approach may facilitate earlier diagnosis, guide therapeutic innovation, and ultimately prevent irreversible ocular morbidity.

2. Molecular Pathways of Eyelid Skin Inflammation

Eyelid inflammation arises from a complex interplay of immune and non-immune pathways. Central processes include epithelial barrier disruption, activation of adaptive immunity, and cytokine-driven signaling cascades. Collectively, these mechanisms promote chronic tissue remodeling, fibrosis, and glandular dysfunction, which characterize autoimmune-mediated diseases of the eyelid skin and ocular adnexa.

2.1. Cytokine and T Cell Pathways

Dysregulated T helper (Th) subsets dominate the immune landscape of eyelid inflammation. Increased activity of Th1 and Th17 cells has been demonstrated in both ocular cicatricial pemphigoid (OCP) and Sjögren’s syndrome, accompanied by elevated levels of IL-1β, IL-6, IL-17, TNF-α, and IFN-γ in periocular tissues [2,6]. IL-17 is a key driver of fibroblast activation and conjunctival scarring, whereas TNF-α and IFN-γ sustain chronic inflammatory loops. In contrast, impaired regulatory T cell function reduces immune tolerance and permits uncontrolled autoimmunity [3].

2.2. Autoantibody-Mediated Complement Activation

Humoral immunity plays a central role in several autoimmune eyelid diseases. In OCP, autoantibodies targeting basement membrane zone components such as BP180, BP230, and laminin-332 initiate complement activation and neutrophil recruitment, resulting in subepithelial inflammation and fibrosis [5]. In pemphigus vulgaris and bullous pemphigoid, IgG autoantibodies against desmogleins and hemidesmosomal proteins lead to acantholysis and blistering, which may also involve the eyelid skin.

2.3. Fibroblast and Adipocyte Signaling in Thyroid Eye Disease

In thyroid-associated orbitopathy (TAO), orbital and periocular fibroblasts aberrantly express thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R). Activation of these receptors drives excessive glycosaminoglycan production, adipogenesis, and tissue edema, which clinically manifest as eyelid retraction and periorbital swelling [4]. Genetic studies implicate polymorphisms in co-stimulatory genes, further highlighting the role of immune–stromal interactions in TAO pathogenesis [9].

2.4. Role of Microbiome and Innate Immunity

Increasing evidence supports a contribution of the periocular microbiome to eyelid inflammation. Overgrowth of Demodex mites and altered colonization by Corynebacterium species can activate toll-like receptor (TLR) pathways, inducing IL-8 and matrix metalloproteinases that damage the eyelid margin. Such dysbiosis-driven inflammation provides a mechanistic link between chronic blepharitis and systemic autoimmunity, where innate immune activation lowers the threshold for adaptive responses [1,11].

2.5. Oxidative Stress and Epithelial Barrier Dysfunction

Oxidative stress acts as a potent amplifier of inflammatory signaling. In both TAO and OCP, reactive oxygen species (ROS) upregulate NF-κB activity, enhancing transcription of pro-inflammatory cytokines and adhesion molecules. This cascade compromises epithelial barrier integrity, perpetuates inflammation, and contributes to irreversible tissue remodeling [10,12].

2.6. Summary

Collectively, these molecular insights underscore that eyelid inflammation is not an isolated process but a reflection of systemic immune dysregulation. They also point to promising therapeutic targets, including IL-17, TNF-α, T cell co-stimulatory pathways, and microbiome-directed interventions, which may shape the next generation of precision therapies.

3. Autoimmune Diseases Involving Eyelid Skin and Ocular Adnexa

Autoimmune diseases represent a major cause of eyelid skin inflammation. Their manifestations in the ocular adnexa extend beyond cosmetic changes, frequently leading to significant visual morbidity. Pathogenesis involves diverse immune mechanisms, including autoantibody-mediated complement activation, T cell–driven cytokine responses, and stromal tissue remodeling. Below, we summarize the principal autoimmune diseases with eyelid involvement, emphasizing their molecular basis, clinical presentation, and therapeutic implications.

3.1. Ocular Cicatricial Pemphigoid (OCP)

OCP is a chronic, progressive autoimmune blistering disease characterized by subepithelial fibrosis of the conjunctiva, eyelid skin, and mucous membranes. Autoantibodies against basement membrane zone antigens (BP180, BP230, laminin-332) activate complement and recruit neutrophils, resulting in inflammation and fibrosis [5]. Clinically, this process causes conjunctival scarring, symblepharon formation, and cicatricial entropion with trichiasis, severely compromising the ocular surface. Eyelid skin involvement may include erythema, scarring, and keratinization. At the molecular level, Th2 and Th17 cytokines, particularly IL-17, drive fibroblast activation and extracellular matrix deposition [2,13]. Without timely immunosuppression, OCP progresses relentlessly, highlighting the need for early recognition.

3.2. Pemphigus Vulgaris and Bullous Pemphigoid

Pemphigus vulgaris is mediated by IgG autoantibodies targeting desmoglein-1 and desmoglein-3, leading to acantholysis and intraepithelial blistering. Although the oral mucosa is most frequently involved, periocular skin may also exhibit erosions and ulcerations. By contrast, bullous pemphigoid involves hemidesmosomal proteins, producing subepidermal blistering. Eyelid manifestations include erythematous plaques, crusting, and secondary infections, which can mimic chronic blepharitis and delay diagnosis [14,15]. Direct immunofluorescence remains the diagnostic gold standard.

3.3. Thyroid-Associated Orbitopathy (TAO)

TAO, or thyroid eye disease, is the most common autoimmune disorder affecting the eyelids. Autoreactive T cells target TSHR and IGF-1R on orbital fibroblasts, driving glycosaminoglycan production, adipogenesis, and edema [4]. Clinically, eyelid retraction occurs in up to 90% of cases [7], accompanied by periorbital edema and dermopathy. Oxidative stress and NF-κB activation amplify cytokine release, perpetuating tissue remodeling. Recent trials demonstrate that teprotumumab, an IGF-1R inhibitor, effectively reduces eyelid and orbital inflammation [9,10], underscoring the translational impact of molecular discoveries.

3.4. Systemic Lupus Erythematosus (SLE)

SLE is a systemic autoimmune disease with frequent cutaneous manifestations, including the periocular region. Discoid lesions and malar rashes may extend to the eyelids, presenting with erythema, scaling, and dyspigmentation. Histologically, immune complex deposition at the dermoepidermal junction activates complement and recruits inflammatory infiltrates. Type I interferon pathways, particularly IFN-α–inducible genes, play a central role in perpetuating cutaneous inflammation. Eyelid involvement, though less common than systemic disease, may mimic other dermatoses and contribute to ocular surface instability [16,17].

3.5. Sjögren’s Syndrome

Sjögren’s syndrome primarily affects the exocrine glands. Periocular manifestations result from lymphocytic infiltration of the lacrimal glands, leading to aqueous tear deficiency, and of the meibomian glands, causing lipid layer instability. Chronic eyelid margin inflammation drives meibomian gland dysfunction, blepharitis, and keratoconjunctivitis sicca. Molecular drivers include Th17 cytokines (IL-17, IL-22) and B cell hyperactivity. Pediatric cases, though rare, often present with ocular signs that precede systemic disease [6,18].

3.6. Sarcoidosis and Granulomatous Disorders

Sarcoidosis is a systemic granulomatous disease in which periocular involvement occurs in 10–15% of patients, manifesting as eyelid nodules, erythema, or diffuse edema. Histopathology demonstrates non-caseating granulomas composed of epithelioid histiocytes and multinucleated giant cells. Cytokines such as TNF-α, IL-2, and IFN-γ drive granuloma formation, linking sarcoidosis to broader Th1-mediated immune pathways [14]. Eyelid sarcoid lesions may clinically resemble malignancies, complicating differential diagnosis.

3.7. Other Rare Autoimmune and Autoinflammatory Syndromes

Several rare disorders can involve the eyelids. VEXAS syndrome, caused by somatic mutations in UBA1, presents with systemic autoinflammation and ocular adnexal manifestations, including eyelid swelling and orbital inflammation. Immune-related adverse events from checkpoint inhibitors may also induce periocular granulomas, reflecting the expanding spectrum of autoimmune phenomena affecting the eyelids [3,8,15].

3.8. Summary

Autoimmune diseases involving the eyelid skin encompass a diverse group of disorders unified by chronic immune dysregulation and overlapping molecular pathways. Recognition of periocular manifestations is critical, as they may represent the first sign of systemic disease. Advances in molecular diagnostics and targeted therapies—including B cell depletion, cytokine inhibition, and receptor blockade—hold promise for earlier intervention and improved patient outcomes (Table 1).

4. Clinical Implications and Diagnostics

Accurate diagnosis of autoimmune-mediated eyelid inflammation requires a multimodal strategy that combines clinical evaluation with histopathology, immunological assays, and advanced imaging. Because eyelid manifestations may precede systemic disease, early recognition is essential to prevent irreversible ocular morbidity.

4.1. Clinical Examination and Differential Diagnosis

Slit-lamp biomicroscopy remains the cornerstone of periocular assessment. Eyelid margin changes—such as telangiectasia, scarring, trichiasis, and keratinization—are highly suggestive of autoimmune cicatricial disease, including ocular cicatricial pemphigoid (OCP) [2,5]. Differentiation from chronic blepharitis or infectious etiologies is critical, as delayed recognition permits progression of fibrosis. Standardized clinical grading systems, such as the Foster staging system for OCP and the Clinical Activity Score (CAS) for thyroid-associated orbitopathy (TAO), provide objective measures of severity and guide treatment [7].

4.2. Histopathology and Direct Immunofluorescence

Biopsy of conjunctiva or eyelid skin remains the diagnostic gold standard in autoimmune blistering diseases. In OCP, subepithelial fibrosis with lymphocytic infiltration is typical, while direct immunofluorescence reveals linear deposition of IgG, IgA, and complement (C3) along the basement membrane zone. In pemphigus vulgaris, intraepidermal acantholysis is evident, with intercellular IgG deposition against desmogleins. Immunopathological confirmation is therefore critical for distinguishing autoimmune disease from infectious or neoplastic mimics [19,20].

4.3. Advanced Imaging Modalities

Innovations in ophthalmic imaging have expanded diagnostic capabilities. In vivo confocal microscopy (IVCM) enables high-resolution visualization of epithelial alterations and inflammatory infiltrates, providing a non-invasive complement to biopsy. Anterior segment optical coherence tomography (AS-OCT) offers cross-sectional views of eyelid margins and conjunctival scarring, allowing longitudinal monitoring in OCP and TAO [21]. These modalities are increasingly integrated into clinical trials as quantitative endpoints for disease progression and therapeutic efficacy.

4.4. Molecular Biomarkers in Tears and Serum

Molecular profiling of tears has revealed elevated levels of IL-6, IL-17, TNF-α, and matrix metalloproteinase-9 (MMP-9) in patients with OCP, TAO, and Sjögren’s syndrome, correlating with disease severity. Serum biomarkers—such as anti-BP180 and anti-laminin-332 autoantibodies in OCP, and thyroid-stimulating immunoglobulins (TSI) in TAO—are increasingly used for diagnosis and monitoring. Genetic polymorphisms in co-stimulatory pathways and markers of oxidative stress have been linked to more aggressive phenotypes. These molecular signatures may help stratify patients and tailor therapeutic choices [22,23,24,25].

4.5. Integration of Diagnostics into Personalized Medicine

The integration of histopathology, imaging, and molecular biomarkers is reshaping diagnostic paradigms. Artificial intelligence (AI)-based image analysis holds promise for improving diagnostic accuracy by enabling stratifying patients toward precision therapies. Furthermore, multi-omics approaches—including genomics, proteomics, and metabolomics—may enable early identification of high-risk patients and support biomarker-driven treatment algorithms [26,27,28].

4.6. Summary

The diagnostic approach to autoimmune-mediated eyelid inflammation increasingly relies on a multimodal framework. While biopsy and immunofluorescence remain central, advances in imaging and biomarker discovery are enhancing diagnostic precision and disease monitoring. Together, these innovations pave the way toward personalized medicine strategies, offering the potential to transform clinical outcomes in patients with autoimmune eyelid disease (Table 2).

5. Therapeutic Strategies

Management of autoimmune-mediated eyelid inflammation requires an individualized approach that addresses both local manifestations and systemic disease activity. Advances in molecular insights have reshaped therapeutic paradigms, particularly in ocular cicatricial pemphigoid (OCP), pemphigus, and thyroid-associated orbitopathy (TAO), where periocular involvement is prominent.

5.1. Conventional Immunosuppressive Therapy

Systemic corticosteroids remain the first-line treatment for acute exacerbations, rapidly suppressing inflammation and preventing fibrotic progression. However, their long-term use is constrained by adverse effects such as skin atrophy, infection, osteoporosis and ocular hypertension. For chronic control, antimetabolites—including azathioprine, mycophenolate mofetil, and methotrexate—serve as steroid-sparing agents in OCP and pemphigus. Cyclophosphamide is reserved for severe, vision-threatening cases with progressive scarring.

Topical therapies complement systemic treatment. Corticosteroid ointments and calcineurin inhibitors (tacrolimus, cyclosporine A) provide local control of eyelid inflammation [29,30]. Topical tacrolimus reduces erythema and scarring in OCP, while cyclosporine eye drops improve eyelid margin inflammation and tear film stability in autoimmune blepharitis, particularly in Sjögren’s syndrome [6]. Combining systemic and local therapy enhances efficacy while limiting systemic toxicity.

5.2. Biologic Agents

Biologic therapies have revolutionized management of refractory disease. Rituximab (anti-CD20) induces sustained remission in OCP and pemphigus by depleting autoreactive B cells. TNF-α inhibitors (infliximab, adalimumab) are occasionally used in pemphigoid and lupus with periocular involvement, though responses are variable [31].

TAO has emerged as a paradigm for biologic therapy. Teprotumumab, an IGF-1R–blocking antibody, is the first targeted treatment approved for TAO, demonstrating significant improvement in eyelid retraction and orbital inflammation. Biologics targeting IL-6 (tocilizumab) and IL-17 are under active evaluation and may further expand precision therapy options [4,7,32].

5.3. Small Molecules and Targeted Oral Therapies

Janus kinase (JAK) inhibitors such as baricitinib and tofacitinib block intracellular cytokine signaling (IL-6, IL-17, IFN-γ), reducing inflammation and stabilizing scarring in refractory autoimmune blistering diseases. Their oral administration and multi-cytokine blockade make them attractive for long-term therapy, though monitoring is required for infection and thrombotic risk [33,34].

Other small molecules, such as apremilast (PDE-4 inhibitor), have shown efficacy in cutaneous autoimmune disease and may benefit periocular lesions. While data for eyelid disease remain limited, emerging evidence suggests potential roles in chronic, treatment-resistant inflammation [35].

5.4. Local Adjunctive Therapies

Local interventions are crucial for structural complications. Trichiasis from cicatricial entropion may require epilation, electrolysis, or cryotherapy, while severe cases necessitate reconstructive surgery, including mucous membrane or amniotic membrane grafts (AMG) [2].

Device-based adjuncts, such as thermal pulsation and meibomian gland expression, improve lipid secretion and reduce chronic eyelid inflammation. Light-based modalities—including intense pulsed light (IPL) and low-level light therapy (LLLT)—have shown benefit in chronic blepharitis overlapping with autoimmune disease, reducing vascular congestion and inflammatory cytokine activity [36,37].

5.5. Lifestyle and Supportive Interventions

Supportive measures are integral to long-term care. Selenium supplementation improves outcomes in TAO, while antioxidant-rich diets (e.g., Mediterranean diet) reduce systemic oxidative stress and NF-κB activation. Smoking cessation is essential, as smoking is a major risk factor for TAO progression and poor therapeutic response [10,11].

Adjunctive ocular surface care (warm compresses, eyelid hygiene, preservative-free lubricants) improves comfort and reduces secondary infections in autoimmune blepharitis.

5.6. Toward Personalized Immunotherapy

Molecular diagnostics are enabling biomarker-driven therapeutic choices. Tear proteomic studies identify IL-6, IL-17, TNF-α, and MMP-9 as correlates of severity, while genetic profiling (e.g., co-stimulatory polymorphisms) may predict aggressive phenotypes. Patients with Th17-dominant disease may respond best to IL-17 inhibition, whereas B cell–driven disease benefits from rituximab. Microbiome-targeted approaches, including probiotics or selective antibiotics, represent emerging strategies for periocular autoimmune control [9,38].

5.7. Summary

Current management of autoimmune-mediated eyelid inflammation spans conventional immunosuppression, biologics, small molecules, and adjunctive local therapies. The shift from broad immunosuppression toward biomarker-guided, precision interventions marks a paradigm change in treatment. Integration of systemic, local, and lifestyle approaches—anchored in molecular profiling—promises improved efficacy, reduced toxicity, and a future of personalized immunotherapy for eyelid autoimmune disease.

6. Future Directions

The future management of autoimmune eyelid disease is expected to be shaped by precision medicine, integrating molecular diagnostics, targeted therapies, microbiome modulation, and digital health. While current approaches rely on broad immunosuppression and biologics, several research avenues promise to transform the field.

6.1. Biomarker Development and Multi-Omics Approaches

Advances in high-throughput sequencing and proteomics are reshaping the understanding of eyelid inflammation. Tear proteomics has already identified cytokines and proteases—including IL-17, IL-6, TNF-α, and MMP-9—that correlate with disease severity. Future validation of these markers could enable earlier detection of aggressive phenotypes. Integrative multi-omics strategies combining genomics, transcriptomics, proteomics, and metabolomics are likely to uncover new pathways driving fibrosis and keratinization in autoimmune blistering diseases [38,39,40]. Integration of omics datasets with imaging may support risk stratification and prediction of therapeutic response.

6.2. Microbiome and Immune Modulation

The periocular microbiome represents an emerging therapeutic frontier. Dysbiosis, including overgrowth of Demodex mites and Corynebacterium species, has been implicated in chronic eyelid inflammation [1,11]. Future interventions may include selective antibiotics, probiotics, or microbiota transplantation to restore immune tolerance and reduce flares. Identification of microbial metabolites influencing T cell differentiation could further illuminate the skin–immune interface at the eyelid.

6.3. Novel Targeted and Localized Therapies

Next-generation therapies are moving beyond current biologics. JAK inhibitors and IL-17/IL-23 antagonists are under investigation for autoimmune blistering diseases, with topical formulations being explored for periocular application. Nanotechnology-based delivery platforms may enable localized immunomodulation, such as nanoparticle-encapsulated corticosteroids or siRNA against pro-fibrotic genes, minimizing systemic toxicity [41,42].

6.4. Artificial Intelligence and Digital Health

Artificial intelligence (AI) and digital technologies are poised to enhance diagnosis and monitoring. Machine learning applied to eyelid photography and anterior segment OCT can facilitate automated detection of early cicatricial changes. Remote monitoring through smartphone-based imaging could extend disease tracking beyond clinic visits. Ultimately, AI-driven integration of imaging, clinical, and biomarker data may enable personalized treatment algorithms and prediction of disease flares [43,44,45].

6.5. Patient-Centered and Preventive Strategies

Future research must also prioritize patient-reported outcomes and prevention. Chronic eyelid inflammation contributes to functional impairment, cosmetic disfigurement, and psychological burden. Clinical trials incorporating both molecular and quality-of-life endpoints will be essential. Moreover, genetic and biomarker-based screening could identify high-risk individuals, enabling early intervention before irreversible fibrosis occurs [46,47,48,49].

6.6. Summary

The field is moving decisively toward biomarker-guided, microbiome-informed, and digitally supported precision medicine. By integrating molecular research, targeted therapies, and patient-centered strategies, future approaches hold the potential to revolutionize outcomes and quality of life for individuals with autoimmune-mediated eyelid skin inflammation.

7. Conclusions

Autoimmune diseases of the eyelid skin represent a unique bridge between dermatology, ophthalmology, and immunology. Once considered secondary to systemic manifestations, periocular involvement is now recognized as a clinically and biologically significant feature. The delicate structure of the eyelid, coupled with constant environmental exposure, makes it a sensitive indicator of immune dysregulation. Recognizing eyelid inflammation as more than a local phenomenon is critical for improving diagnosis, therapy, and patient outcomes.

At the molecular level, cytokine imbalance, autoantibody-driven complement activation, and fibroblast remodeling underlie chronic eyelid inflammation. Dysregulated Th1, Th2, and Th17 pathways, together with impaired regulatory T cell activity and microbial dysbiosis, explain the heterogeneity of clinical presentations. These findings emphasize the systemic dimension of eyelid disease.

Clinically, periocular inflammation is not only disfiguring but often vision-threatening, with OCP, pemphigus, TAO, and Sjögren’s syndrome frequently beginning with subtle eyelid signs. If unrecognized, these changes may progress to fibrosis, trichiasis, and severe ocular surface disease. The eyelid thus acts as a sentinel structure, signaling systemic activity and demanding multidisciplinary evaluation.

Therapeutically, the shift from broad immunosuppression to targeted approaches—exemplified by rituximab, teprotumumab, and JAK inhibitors—represents a major advance. Adjunctive surgical and device-based interventions expand treatment options, although challenges remain in ensuring accessibility, long-term safety, and personalization.

Looking ahead, biomarker-guided therapy, multi-omics integration, and AI-driven diagnostics promise earlier detection, tailored treatment, and prevention of irreversible damage. Incorporating patient-centered outcomes will be equally important, reflecting the profound psychosocial and visual impact of periocular disease.

In conclusion, autoimmune eyelid inflammation exemplifies the convergence of local and systemic immune dysregulation. Integration of molecular discoveries, advanced diagnostics, and targeted therapeutics heralds a new era of precision medicine in periocular autoimmune disease. Continued interdisciplinary collaboration will be essential to translate these insights into tangible improvements in patient care and to establish the eyelid as both a clinical marker and a therapeutic frontier in autoimmune disease.