small molecules

2026-08-04 | The Past, the Present, and the Future of Periostin in Allergy.

Periostin is a matricellular protein that binds to its receptors, which include several integrin molecules but mainly αvβ3 integrin on cell surfaces, thereby transducing its signals into cells. Almost 20 years have passed since we found that periostin is involved in the pathogenesis of asthma, which marked the first evidence of its involvement in allergic diseases. Over the past 2 decades, cumulative evidence has demonstrated that periostin plays important roles in the onset or progress of many allergic diseases such as chronic rhinitis with nasal polyp, atopic dermatitis (AD), allergic conjunctivitis, eosinophilic esophagitis, eosinophilic otitis media, allergic rhinitis, and eosinophilic granulomatosis with polyangiitis. Starting from the observation of highly expressed periostin in the lesions of these diseases, periostin studies have expanded to include how periostin contributes to the generation of allergic phenotypes, how measurement of periostin is useful as a biomarker for allergic diseases, and recently how periostin inhibitors can improve allergic diseases. Periostin contributes to the generation of allergic phenotypes by acting as a matricellular protein on many cells, including both non-immune and immune cells. Based on the characteristics of periostin as a surrogate biomarker of interleukin-13, a signature cytokine of type 2 inflammation, serum periostin has been used as a biomarker for stratifying endotypes, estimating disease severity, predicting or monitoring the efficacy of therapeutic drugs, and predicting disease relapse or recurrence. Moreover, a lot of attention is now being paid to periostin in body fluids such as tears and sputum as a biomarker directly reflecting type 2 inflammation. Since it has been shown that periostin evokes itch in AD, we hope to see the development of a novel therapeutic agent for AD targeting periostin/αvβ3 integrin. Here we summarize the discovery and characteristics of periostin, as well as questions and/or problems regarding periostin that remain to be resolved.

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2026-08-03 | An interdisciplinary framework for management of ocular allergy: Integrating the allergist in clinical practice.

Ocular allergy represents one of the most frequent yet under-recognized manifestations of pediatric allergic disorders, affecting up to 30% of children worldwide. The disease encompasses a spectrum ranging from mild, intermittent seasonal or perennial allergic conjunctivitis to severe, vision-threatening forms such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). Despite its high prevalence and the strong association with systemic allergic diseases-including asthma, allergic rhinitis, and atopic dermatitis-the involvement of pediatric allergists in routine ocular allergy care remains limited. This review proposes an interdisciplinary framework that integrates allergists more centrally into ocular allergy management. A structured approach to diagnosis highlights the allergist's essential role in identifying systemic triggers, performing allergy testing, and differentiating ocular allergy from mimics such as viral conjunctivitis, blepharitis, and autoimmune ocular surface disease. Management, as a stepwise, collaborative strategy beginning with allergen avoidance and topical dual-acting antihistamine/mast-cell stabilizers, progressing to steroid-sparing immunomodulators, systemic therapy, and advanced options such as allergen immunotherapy, emerging biologic treatments, including omalizumab and dupilumab, is discussed in the context of severe VKC and AKC, along with benefits, limitations, and need for ophthalmic oversight. This framework underscores the importance of timely referral from ophthalmologists to pediatric allergists, co-management of complex cases, and early integration of systemic allergy care. Through interdisciplinary collaboration, long-term visual outcomes can be improved and inappropriate steroid use minimized. A practical interdisciplinary care pathway and treatment escalation algorithm are proposed to facilitate real-world collaborative management.

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2026-07-01 | Efficacy of topical 0.05% cyclosporine in Vernal Keratoconjunctivitis in children aged 5-15 years visiting outpatient department

Purpose:To assess the effectiveness and safety of short-term use of topical 0.05% cyclosporine in children with Vernal Keratoconjunctivitis (VKC).Study Design: Quasi experimental study. Place and Duration of Study: Sheikh Zayed Medical College and Hospital in Rahim Yar Khan from April 2025 to September 2026. Methods: A Consecutive sampling was done to include 78 children of 5-15 years of age who had clinically identified VKC. The analysis involved one eye of each patient. They were treated with the topical cyclosporine 0.05% eye drops four times per day for one month. The severity of the disease was evaluated using a validated clinical scoring system that included symptoms and indicators at baseline and after one month. Treatment was considered effective if there was at least one point improvement in the total VKC score from baseline. Results: There were 65.4% males. The total VKC score dropped significantly from the baseline of 10.0 [IQR: 8.0-13.0] to 4.0 [IQR: 2.0-6.0] after one month (p <0.001). Clinical improvement was noted in 69 patients (88.5%). No substantial differences in treatment response were observed based on age, gender, duration of symptoms, or daily computer usage. A mild, temporary burning sensation was observed in 7% of individuals. Conclusion: Topical 0.05% cyclosporine provided substantial short-term therapeutic improvement and exhibited a positive safety profile in pediatric patients with VKC.Larger, randomized controlled trials with longer follow-up are needed to confirm these preliminary findings and to establish the long-term role of this treatment in VKC management.

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2026-07-01 | Clinical Profile and Recurrence Patterns of Vernal Keratoconjunctivitis in a Tertiary Care Setting

Abstract Background: Vernal keratoconjunctivitis (VKC) is a chronic allergic condition of the ocular surface that primarily affects youngsters in the tropical and subtropical areas. Understanding how diverse anatomical disease patterns influence recurrence is critical for effective therapy. The purpose of this study was to investigate the clinical profile of VKC patients and determine the relationship between illness pattern and recurrence of episodes. Materials and Methods: This hospital-based, cross-sectional, and observational study included 132 VKC patients presenting to a tertiary care ophthalmology center. Patients were classified into limbal, palpebral, or mixed patterns based on anatomical involvement. Demographic data, clinical features, and episode patterns (initial vs. recurrent) were recorded. The Chi-square tests assessed the associations between disease pattern and clinical variables. Results: The cohort comprised 85 males (64.39%) and 47 females (35.61%), with 72.73% aged ≤10 years. Itching (81.82%) and redness (66.67%) were predominant symptoms. Limbal VKC was most common (59.09%), followed by mixed (24.24%) and palpebral (16.67%) patterns. Overall recurrence rate was 78.79%, with mixed pattern showing highest recurrence (93.75%) and palpebral the lowest (54.55%). Disease pattern showed highly significant association with the type of episode ( χ 2 = 12.05, P = 0.002). Palpebral VKC presented more commonly as initial episodes (35.71%), while mixed pattern was strongly associated with recurrence (28.85% in recurrent vs. 7.14% in initial episodes). Conclusion: VKC demonstrates distinct clinical phenotypes with significant association between disease pattern and chronicity. Mixed VKC was significantly associated with higher recurrence rates and greater symptom burden in this cohort. Disease pattern was significantly associated with recurrence and symptom burden in this cross-sectional sample.

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2026-06-27 | A clinical study on patterns of vernal keratoconjunctivitis among children in rural part of North-East India

Objectives: The objective of the study is to evaluate the demographic profile, clinical patterns, and environmental risk factors of vernal keratoconjunctivitis (VKC) among children attending a tertiary care center in a rural region of North-East India. Material and Methods: This hospital-based descriptive cross-sectional study was conducted from February 2024 to January 2025. It included 100 children (aged 0–18 years) clinically diagnosed with VKC. Data regarding demographics, clinical signs, symptoms, and environmental exposures (including cooking fuel and animal contact) were collected using a structured pro forma. Results: The mean age of presentation was 12.02 years, with a significant male preponderance (male: female ratio 2.03:1). Symptom exacerbation peaked in May. The most common symptom was intense itching (91%), and the most common sign was conjunctival hyperemia (88%). The Limbal variant was the predominant phenotype (72%). A significant association was observed with the use of firewood/kerosene for indoor cooking. Conclusion: VKC in North-East India predominantly affects young males and presents chiefly as the Limbal form. Indoor air pollution from biomass fuels is a significant modifiable risk factor in this rural population.

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antibodies

2026-05-01 | A27-06 Off-Label Use of Type 2 Targeted Biologic Therapies in Pediatric Pulmonology and Allergy: A National Multicenter Cohort Study (France, 2005-2025)

Abstract Context In pediatrics, access to biologic therapies targeting type 2 inflammation remains limited by age and indication restrictions within marketing authorizations (MA). Real-world data on off-label use are lacking. We aimed to describe national prescribing practices, efficacy, and safety of anti-Th2 biologics used outside MA recommendations in French pediatric pulmonology and allergy centers. Methods We conducted a retrospective, observational, multicenter study including children (0-18 yrs) treated off-label between 2005 and 2025 with omalizumab, dupilumab, mepolizumab, or tezepelumab. Data were collected through a standardized anonymized form across seven tertiary hospitals affiliated with the RespiRare® network and the French Society of Allergy. The primary endpoint was characterization of off-label prescribing circumstances (indication, rationale, and regulatory framework). Secondary endpoints were clinical efficacy and safety. Results Eighty-eight children were included (omalizumab = 78 [89%], dupilumab = 8 [9%], mepolizumab = 1, tezepelumab = 1). Off-label prescriptions involved food allergy (35), severe asthma (32), vernal keratoconjunctivitis (10), allergic bronchopulmonary aspergillosis in cystic fibrosis (6), chronic urticaria (3), nasal polyposis (1), and macrophage activation syndrome (1). Sixty percent concerned diseases without any pediatric MA in France; 40% did not meet eligibility criteria (mainly age &lt; 6 years or IgE/eosinophil levels outside authorized ranges). All prescribers justified off-label use by lack of therapeutic alternatives (59% inefficacy or intolerance to standard care; 41% absence of approved therapy). Prescriptions were validated in multidisciplinary meetings (local 53%, national 34%). Adverse events occurred in 14% of omalizumab-treated patients (mainly mild injection-site pain, fatigue, headache); three discontinued treatment. No serious events were reported with other biologics. Among asthmatic children (n = 32), severe exacerbations decreased from a median 3 [2-8] to 0 [0-1.2] per year (p &lt; 0.0001), with significant improvement in AQLQ (1.7→6.1; p &lt; 0.0001) and c-ACT scores (12→22; p = 0.003). In food-allergic children, the tolerated milk protein dose rose from 16.5 g to 255 g (p = 0.002), with smaller skin-prick diameters. Conclusions This first French nationwide cohort documents real-world off-label use of Th2-targeted biologics in children with severe or rare respiratory/allergic disorders. Off-label prescribing was medically driven, well-tolerated, and associated with meaningful clinical improvement. These findings support the development of prospective registries and may inform future pediatric MA extensions and personalized treatment strategies in severe pediatric asthma and allergic diseases. This abstract is funded by: No

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2026-04-16 | Pediatric Ocular Surface Disorders

Ocular surface disorders in the pediatric population constitute a clinically demanding group of conditions that differ substantially from their adult counterparts, both in their underlying mechanisms and in the way they present. The immature corneal innervation, the evolving tear film composition, and the immunologically active conjunctiva-associated lymphoid tissue of the developing eye collectively create a milieu in which inflammatory and hypersensitivity responses can be intense, yet symptoms may remain subtle or absent. Children frequently cannot articulate their discomfort, and the clinician must rely on behavioral cues — persistent eye rubbing, photophobia, recurrent redness — as well as objective findings to reach a timely diagnosis. Delay carries a real cost: amblyopia, irreversible corneal scarring, and the compounding effects of chronic illness during critical windows of visual development. This chapter covers the full spectrum of pediatric ocular surface disease, from allergic conditions including vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis, to infectious keratoconjunctivitis, pediatric blepharokeratoconjunctivitis, phlyctenular keratoconjunctivitis, ocular rosacea, and dry eye disease, as well as the severe, sight-threatening sequelae of Stevens-Johnson syndrome and ocular graft-versus-host disease. Current management strategies are discussed with an emphasis on early immunomodulation, steroid-sparing regimens, and the emerging role of biologic therapies and regenerative medicine in children who do not respond to conventional treatment. Pediatrik popülasyonda oküler yüzey hastalıkları, hem altta yatan mekanizmalar hem de klinik prezentasyon açısından erişkin hastalıktan belirgin biçimde ayrılan, tanısal ve terapötik güçlükler sunan geniş bir hastalık grubunu oluşturmaktadır. Gelişmekte olan gözde immatür korneal innervasyon, olgunlaşma sürecindeki gözyaşı filmi bileşimi ve immünolojik açıdan aktif konjonktiva ilişkili lenfoid doku bir arada, inflamatuar ve aşırı duyarlılık yanıtlarının şiddetli seyredebildiği ancak semptomların zaman zaman silik ya da hiç olmadığı özgün bir ortam oluşturur. Çocuklar şikayetlerini çoğunlukla ifade edemediğinden klinisyen, tanıya ulaşmak için ısrarcı göz ovma, fotofobi ve tekrarlayan kızarıklık gibi davranışsal ipuçlarına ve nesnel bulgulara dayanmak durumundadır. Tanının gecikmesi; görsel gelişimin kritik dönemlerinde ambliopi, geri dönüşü olmayan korneal skar ve kronik hastalığın biriken etkileri şeklinde somut maliyetler doğurmaktadır. Bu bölüm, vernal keratokonjonktivit, atopik keratokonjonktivit ve dev papiller konjonktivit dahil alerjik hastalıklar ile enfeksiyöz keratokonjonktivit, pediatrik blefarokeratokonjonktivit, flikteniüler keratokonjonktivit, oküler rozasea ve kuru göz hastalığının yanı sıra Stevens-Johnson sendromu ve oküler graft-versus-host hastalığının ciddi, görme tehdidi oluşturan sekellerini kapsayan pediatrik oküler yüzey hastalıklarının tüm spektrumunu ele almaktadır. Güncel tedavi stratejileri; konvansiyonel tedaviye yanıtsız çocuklarda erken immünomodülasyon, steroid koruyucu rejimler ve biyolojik ajanlar ile rejeneratif tıbbın gelişen rolüne vurgu yapılarak tartışılmaktadır.

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2026-03-28 | Pediatric Vernal Keratoconjunctivitis (VKC): Current State and Future Directions-A Narrative Review of Clinical Features, Diagnostic Strategies, and Emerging Therapies.

Vernal keratoconjunctivitis (VKC) represents far more than a typical allergic eye disease. It is a distinct and often underestimated chronic inflammatory condition that primarily affects children during critical stages of physical and emotional development. Though frequently grouped with seasonal allergic conjunctivitis, VKC differs significantly in its immunopathology, clinical presentation, and long-term implications. Its intense ocular symptoms and its potential for corneal damage and substantial psychosocial burden require, rather than symptom control, coordinated and multidisciplinary management. This narrative review explores VKC from every angle, with a particular focus on its implications for pediatric care. VKC, in fact, represents a genuine clinical challenge: as its symptoms can mimic milder forms of conjunctivitis, its course is often unpredictable, and its treatment requires balancing efficacy and safety in vulnerable age groups. We examined the immunological mechanisms that make it a model of localized Th2 inflammation, the diagnostic pitfalls that delay recognition, and the evolving treatment landscape, from conventional therapies like cyclosporine A and tacrolimus to innovative agents such as omalizumab and dupilumab. We also highlighted the role of emerging biomarkers, the influence of environmental and microbiome factors, and the urgent need for standardized care pathways. As research continues to expand our understanding, VKC is emerging as a prime example of how personalized medicine and translational science can intersect to address complex immune-mediated diseases in children. For the ones treating pediatric allergic disorders, VKC is no longer a rare curiosity: it is a clinical challenge worth understanding deeply.

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2026-01-05 | Off-label applications of omalizumab: Current insights and perspectives.

Omalizumab is a humanized monoclonal antibody that binds free IgE. Consequently, it exhibits inhibitory properties against allergic cascades. Over the past 20 years, omalizumab has been in the market, and studies have shown its strong tolerability and safety profile. Since 2003 in the United States of America and 2005 in Europe, omalizumab has been available to patients as a therapeutic option. In Europe, it is registered for the treatment of allergic asthma, chronic spontaneous urticaria, and chronic sinusitis with polyps. In the United States, it has been registered for the treatment of allergic asthma, chronic spontaneous urticaria, and chronic food allergies in children over 1 year of age. With a universal target point for most allergic conditions, omalizumab has the potential to become the most versatile biological drug for allergologists. The literature describes numerous uses of omalizumab as an adjuvant or monotherapy for allergic conjunctivitis, systemic mastocytosis, food allergies, drug hypersensitivity, allergic bronchopulmonary aspergillosis, and allergen immunotherapy, among others. In the following publication, we will provide you with the current knowledge regarding the use of omalizumab in conditions other than those covered by the current product registration.

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2025-12-16 | IL-18 receptor axis in allergic conjunctivitis: a multi-omics study.

The pathophysiology of allergic conjunctivitis (AC) is not fully explained by the traditional Th2-centric model. This study aimed to identify AC-associated candidate genes and delineate immune pathways, with a focus on cell-type-specific mechanisms that could contribute to disease heterogeneity. We employed an integrative multi-omics strategy, using three genomic analyses (FUSION, MAGMA, UTMOST) on human GWAS data to identify AC-associated candidate genes. These candidates were then investigated using single-cell RNA sequencing data from a mouse model of AC to map immune cell communication and signaling dynamics. Key pathways were validated in an independent ovalbumin-induced AC mouse model using clinical scoring, qRT-PCR and Western blot analysis. This approach identified nine high-confidence AC-associated candidate genes, including key components of the IL-1 and Toll-like receptor families. In the AC mouse model, the IL-18 receptor components Il18r1 and Il18rap were selectively upregulated in NK and T cells from allergic versus control mice and correlated positively with interferon-γ (Ifng) expression. Cell-cell communication and pseudotime analyses indicated an allergic-state network characterized by enhanced NK cell-linked IFN-γ signaling to antigen-presenting cells and dynamic changes in NF-κB and JAK-STAT pathway activity. In the OVA-induced model, conjunctival IL-18, IL-18R1, IL-18RAP and phosphorylated NF-κB p65 were increased in AC versus controls and showed a stepwise rise across mild, moderate and severe clinical groups. Across human genetics, single-cell transcriptomics and in vivo validation, an IL-18 receptor/IFN-γ axis in NK and T cells emerges as a reproducible module associated with AC and its severity. These findings extend the immunopathological framework of AC beyond a purely Th2-driven process and nominate IL-18R-linked signaling as a candidate pathway for future mechanistic and therapeutic studies.

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proteins

2026-02-02 | Identification of Treatment Targets in Allergic Conjunctivitis Through Proteome-Scale Mendelian Randomization Analysis.

Allergic conjunctivitis (AC) is a condition with a rising prevalence that occasionally leads to irreversible visual impairment. However, few novel therapeutic targets have been identified for AC. The investigation aims to utilize the Mendelian randomization (MR) technique to explore the causal impacts exerted by the plasma proteome on AC. An evaluation was conducted on a two-sample MR study utilizing 2,940 plasma proteins from the UK Biobank Pharma Proteomics Project (UKB-PPP) to investigate their causal links with AC. Confirmation of these MR results was achieved using Summary-data-based MR (SMR) and Bayesian colocalization techniques. Moreover, evaluations concerning the druggability of proteins, interactions among proteins, and phenome-wide MR (Phe-MR) studies were conducted to ascertain the functionalities of the identified proteins implicated in causality. MR analysis identified five circulating proteins (TLR1, ING1, RALY, CSF2, and ITGAM) whose genetically predicted plasma levels were significantly associated with AC risk (P FDR < 0.05). Functional enrichment analysis of the identified proteins revealed statistically significant biologically relevant pathways, including macrophage activation and pathways of plasma membrane signaling receptor complex, suggesting underlying immune and receptor-mediated mechanisms in AC. SMR and HEIDI validation supports four (TLR1, ING1, ITGAM, and CSF2) of five MR-identified proteins as causal candidates for AC. Subsequent colocalization analysis provided further support for two credible proteins (ING1 and CSF2). Protein druggability suggests CSF2 and ING1 as novel and potentially druggable candidates for AC. Our research identified proteins that appear to have causal effects and could serve as potential therapeutic targets for AC.

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2025-03-01 | Update on pharmaceutical effect of local interferon alfa-2b therapy in ocular surface disorders

In this review study, efficacy and side effects of interferon alfa-2b (IFN-α2b) in treating the common ocular surface disorders is described. It was found that 1 million IU/mL of topical interferon alpha-2b administered four times daily was effective in treating various ocular surface disorders, including vernal keratoconjunctivitis, Ocular surface squamous neoplasia, conjunctival papilloma, and conjunctival melanoma. The treatment showed a significant decrease in symptoms and signs of the diseases and, in some cases, resulted in tumor regression with high tolerance and safety. Irritation was the most common reported adverse effect and complications after treatment with topical IFN-α2b are rare and not severe. IFN-α2b administration intralesionally effectively reduced the conjunctival lymphoma lesions with a dose of 1-1.5 mIU. There is limited reference to mention the effects of this interferon in epidemic keratoconjunctivitis.

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2024-09-22 | Immunotherapy: Current indications and recommendations in the management of ocular allergy.

Allergic diseases, including allergic conjunctivitis (AC), pose a significant health burden, affecting both developed and developing nations. Despite its importance, AC is often underreported, leading to underestimated incidence and prevalence. The coexistence of AC with allergic rhinitis and its comorbidity with asthma underscore its clinical relevance. The prevalence of nasal symptoms with eye symptoms related to eye allergy varies among different age groups and regions worldwide. Climatic factors, aeroallergens, and environmental exposure play significant roles in the prevalence of ocular allergies. Allergen immunotherapy (AIT) represents the only disease-modifying treatment for IgE-mediated allergic diseases. This review provides a comprehensive overview of the history, mechanisms, and evidence of AIT for ocular allergies, with a focus on AC. The primary routes of AIT, subcutaneous immunotherapy (SCIT), and sublingual immunotherapy (SLIT) are discussed in detail. The evidence for AIT in treating AC is extensive and demonstrates its effectiveness in alleviating ocular symptoms, reducing medication usage, and improving the quality of life in patients. Both SCIT and SLIT have shown positive results, with SLIT having a more favorable safety profile. Considerations for initiating and maintaining AIT, including adherence, financial burden, and treatment duration, are highlighted. In summary, AIT is a valuable treatment option for AC, offering long-term symptom relief and potential cost-effectiveness. By understanding the history, mechanisms, and evidence of AIT, healthcare providers can better manage ocular allergies and improve patient outcomes.

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2024-04-15 | TRPV1+ sensory nerves suppress conjunctival inflammation via SST-SSTR5 signaling in murine allergic conjunctivitis.

Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1+ sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1+ sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.

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2024-01-08 | The role of semaphorins in allergic diseases.

Semaphorins were originally identified as guidance molecules in neural development. However, accumulating evidence indicates that 'immune semaphorins' are critically involved in regulating immune cell activation, differentiation, mobility and migration. Semaphorins are also intimately associated with the pathogenesis of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and eosinophilic chronic rhinosinusitis. Interestingly, reflecting their function in positive or negative regulation of immune cells, levels of some semaphorins are increased while others are decreased in patients with allergic diseases. This review presents the pathogenic functions of immune semaphorins in allergic inflammation and discusses the potential use of these molecules as therapeutic targets for allergic diseases.

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cell therapies

2025-08-06 | Emerging concepts in atopic dermatitis and atopic keratoconjunctivitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease involving Th2 cytokine-driven inflammation. AD patients are at risk of developing conjunctivitis, including atopic keratoconjunctivitis (AKC), a sight-threatening chronic allergic eye disease involving both Th2 and Th1/17 cytokine-driven inflammation.In AD, dupilumab is highly effective by inhibiting interleukin (IL)-4 and IL-13. However, some AD patients develop dupilumab-associated ocular surface disease (DAOSD), an AKC-like disease. There are no biomarkers to predict who will develop DAOSD. The purpose of this review is to highlight recent findings in AD and AKC suggesting different immunopathogenic mechanisms are involved. A recent proteomics study of tear fluids identified raised inflammatory markers ( n = 31) in AD patients with DAOSD ( n = 22) and a shift towards a Th1/17 profile. Alternative biologics have been investigated for treating moderate-to-severe AD which have fewer ocular side-effects. The inhibitory effects of dupilumab cause an associated upregulation of IL-33 which could lead to an AKC-like disease. A recent therapeutic approach in AD via regulatory T cells suggests a novel treatment for those at risk of DAOSD. Ocular side-effects of dupilumab suggest that the immunopathogenic pathways in moderate-to-severe AD and AKC are not the same and, for DAOSD, might require different treatment approaches.

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2024-11-15 | Oral mucous membrane tarsal patch grafting: broadening indications and long-term outcomes.

We present the surgical technique of localised excision of tarsal epithelium and replacement with oral mucous membrane tarsal patch grafting (MMTPG), to highlight novel indications of this technique for tarsal surface abnormalities beyond the lid margin. Retrospective case series of patients who underwent MMTPG for refractory tarsal conjunctival disease in three centers, with outcome measures of corneal epitheliopathy, visual acuity (VA), and symptomatic improvement. 8 eyes of 8 patients were included, with surgical indications of medically recalcitrant Vernal Keratoconjunctivitis (VKC) (1), Giant Papillary Conjunctivitis (GPC) (1), or tarsal scarring in the setting of Ocular Cicatricial Pemphigoid (OCP) (2), Stevens-Johnson Syndrome (SJS) (2), advanced Meibomian Gland Dysfunction (MGD) (1) and Ligneous Conjunctivitis (LC) (1). Following MMTPG there were no recurrences of corneal epithelial defects or local tarsal conjunctival pathologies during the follow-up period (mean 28 months). Five eyes demonstrated an improvement in visual acuity of ≥2 Snellen chart lines. Symptomatic improvement was noted in all 8 eyes, and medication requirement was reduced. This report provides a novel conceptual insight to the successful use of MMTPG, highlighting its use in a range of conditions in therapeutically resistant cases.

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2024-08-13 | Combined Papillectomy and Autologous Conjunctival Membrane Graft as Management of Giant Papillae for Severe, Refractory Palpebral Vernal Keratoconjunctivitis-A Case Report.

Introduction: Vernal keratoconjunctivitis (VKC) is an allergic disease that predominantly affects young individuals, with a higher incidence among males. Traditionally seen as a condition of childhood that resolves at puberty, recent studies have shown persistent cases in some individuals, potentially influenced by hot and dry tropical environmental conditions. VKC is more prevalent in regions with a hot and humid climate and a high presence of airborne allergens, leading to significant morbidity and impacting the quality of life for affected individuals. Severe and chronic cases can lead to vision-threatening corneal complications, making effective management crucial. Although the clinical profile of VKC varies geographically, comprehensive studies in specific regions remain limited. Case Presentation: In this case report, we present an 18-year-old male patient with severe and refractory VKC. Despite initial treatments, including topical and oral medications, recurrent episodes occurred every 6 months, accompanied by giant papillae (GP) formation and corneal ulcers. The patient had a history of triamcinolone injection and papillectomy combined with amnion membrane transplantation, but presented with a refractory disease in a year. Surgical intervention involving papillectomy and autologous conjunctival membrane graft was performed, leading to a smooth upper tarsal conjunctiva during the 2-year follow-up period, without GP recurrence and maintaining a clear cornea. The patient's symptoms were effectively managed with topical medications. Conclusion: The management of VKC necessitates a comprehensive approach involving preventive measures, pharmacological treatment, and surgical interventions for refractory cases. This case highlights the potential benefits of surgical techniques, such as papillectomy and autologous conjunctival membrane graft, in managing severe and refractory VKC cases with a history of previous surgical procedure failure. However, it is essential to recognize that exposure avoidance and allergic control remain fundamental in VKC management. Further research and larger studies are required to validate the efficacy of these surgical techniques in managing VKC.

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2024-02-12 | COMBINED PAPILLECTOMY AND AUTOLOGOUS CONJUNCTIVAL MEMBRANE GRAFT AS MANAGEMENT FOR SEVERE, REFRACTORY PALPEBRAL VERNAL KERATOCONJUNCTIVITIS: A CASE REPORT

Introduction : Vernal keratoconjunctivitis (VKC) is a type of allergic conjunctivitis which often occurs repeatedly and chronically. It is unusual compared to other types of conjunctivitis due to its giant papillae (GP) manifestation that may cause serious complication on cornea and eventually lead to permanent vision loss. We present a surgical treatment—resection of GP—in conjunction with autologous conjunctival membrane graft to manage a severe case of VKC.

Case Illustration : An 18-year-old male came with a prior history of recurrent acute allergic keratoconjunctivitis since seven years before. His GP had caused shield-like ulcer, which leads to corneal scar and interferes with his visual acuity. He also had mechanical ptosis due to the giant cobblestones. His symptoms were then managed by performing combined papillectomy and autologous conjunctival membrane graft.

Discussion : During surgery, the GP on both of his eyes were excised until tarsus was visible. Autologous conjunctival membrane was grafted from superior quadrant of each eye, and sutured tightly onto the excised tarsus. Six month postoperatively, his superior tarsal conjunctiva remain relatively smooth, with well-controlled symptoms of keratoconjunctivitis.

Conclusion : Combined papillectomy and autologous conjunctival membrane graft can be considered as an adjunctive intervention to medications, in patients with severe, refractory cases of palpebral vernal conjunctivitis. It can alleviate symptoms and reduce the possibility of permanent damage on corneal tissue.

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2021-08-17 | Allergic conjunctivitis in children: current understanding and future perspectives.

The rising global burden of allergic diseases, particularly in the pediatric population, is of serious concern. Ocular allergy is one of the most common ocular pathologies met in clinical practice. A large proportion of children and adolescents suffer from allergic eye diseases (AEDs), which affect their quality of life. The available treatments and surgical modalities have their limitations and side effects. Therefore, the development of novel and alternate strategies is the need of the hour and requires a timely review of currently available knowledge. The current review covers the incidence and prevalence of AEDs, factors influencing occurrence and severity of AED (age, sex, socioeconomic status etc.), underlying mechanisms, role of allergy testing and immunotherapy in children, development of diagnostic markers and novel therapies including cells and molecules. Understanding the demographics, clinical patterns and risk factors of AED can help formulate appropriate preventive and therapeutic strategies for the effective management of this common cause of ocular morbidity. The future therapeutics for AED seems to rely primarily on cells (mesenchymal stem cells, Tregs, mast cells), cell products, molecules with immunosuppressive potential and immunotherapy.

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2025-10-23 | Ayurvedic Management of Unilateral Vernal Keratoconjunctivitis: A Case Report

Background: Vernal keratoconjunctivitis (VKC) is a chronic allergic ocular disease of childhood, especially in hot and dry climates. In Ayurveda, VKC is discussed in relation to Kaphaja Abhishyanda, a disorder characterized by the aggravation of Kapha and Pitta Dosha resulting in inflammation, congestion, and excessive ocular secretion. Case: A 13-year-old girl presented with unilateral VKC (left eye) with recurrent symptoms despite prior topical corticosteroid use. Baseline findings included conjunctival congestion and superficial corneal vascularization; left-eye visual acuity (LE VA) was LogMAR 1.30. Interventions/Outcomes: A multimodal Ayurvedic regimen was delivered in three inpatient courses over 15 months, consisting of internal formulations, topical eye drops, and ophthalmic procedures. Symptoms of redness, itching, and photophobia improved; corneal vascularization regressed; LE VA LogMAR 1.30→0.47. The patient remained steroid-free at 6-month follow-up. No adverse events were recorded. Conclusion: This case signifies that Ayurvedic interventions can address VKC symptoms along with minimizing corticosteroid dependency. Further clinical trials are necessary to establish Ayurvedic treatments as standard therapy for allergic conjunctivitis.

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2025-05-30 | Ayurvedic Insights Into Abhishyanda: The Role of Dushivisha And Garavisha In Ocular Inflammations

The Ayurvedic concepts of Dushivisha and Garavisha play a significant role in understanding ocular inflammations. Dushivisha, a latent toxin, gradually affects the Netra Srotas, contributing to the chronicity of eye diseases, whereas Garavisha acts as an acute irritant, triggering immediate inflammatory responses. Modern environmental pollution, unhealthy dietary habits, and lifestyle changes exacerbate these toxic influences, leading to various ocular surface diseases. Three case reports are presented to illustrate how both Dushivisha and Garavisha contribute to ocular surface diseases, with a focus on their underlying causes and progression. Role of Dushivisha and Garavisha in Bulbar Vernal Keratoconjunctivitis, Phlyctenular Conjunctivitis, and Simple Conjunctivitis. The Ayurvedic management of these conditions focuses on Shodhana, Sthanika Chikitsa, and Shamana Chikitsa, aiming to restore ocular health by eliminating toxins and strengthening immune function. The paper highlights the relevance of Ayurvedic principles in addressing the root causes of ocular inflammation, emphasizing the importance of lifestyle and dietary modifications alongside traditional therapeutic interventions. This holistic approach provides effective strategies for managing both chronic and acute eye diseases in the context of modern healthcare.

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2025-02-16 | Tolerogenic nanovaccines for the treatment of type I allergic diseases.

The high prevalence of type I allergic diseases such as allergic rhinitis, allergic asthma, food allergies, allergic conjunctivitis, and atopic dermatitis has emerged as a significant public health concern globally. Failure of immune tolerance to ordinarily harmless substances or stimulation, and subsequent induction of T helper 2 cells by antigen-presenting cells evokes the allergic immune response, which results in persistent inflammation, tissue damage, and organ function impairment. Current therapeutic approaches for allergic diseases include avoiding allergen exposure, corticosteroids, biologics, etc. However, these strategies only relieve allergic symptoms but hardly prevent the deteriorative progression and may have adverse effects on patients. With the rapid development of nanotechnology and immunology, emerging tolerogenic nanovaccines represent novel approaches with the potential to cure type I allergic diseases rather than merely alleviate symptoms. In this review, we expound the burgeoning field of tolerogenic nanovaccines against type I allergic diseases, highlight various types of antigens employed in constructing allergen extracts, protein/peptide and nucleic acid-based tolerogenic nanovaccines, and discuss their application in allergic rhinitis, allergic asthma, food allergies, allergic conjunctivitis, and atopic dermatitis.

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2024-09-26 | Development of a Temperature and pH Dual-Sensitive In-Situ Gel for Treating Allergic Conjunctivitis.

The purpose of this study was to improve the efficacy of olopatadine hydrochloride (OT) in treating allergic conjunctivitis (AC). To achieve this goal, we developed an eye formulation without antimicrobial agents using a temperature-pH dual-sensitive in situ gel technology combined with heat sterilization. Various types of carbomers were evaluated and their optimal doses determined. The prescription containing poloxamer 407 (P407) and poloxamer 188 (P188) was optimized using central composite design for response surface methodology (CCD-RSM). The final optimized dual-sensitive in situ gel (TP-gel) consisted of 0.1% olopatadine hydrochloride, 18.80% P407, 0.40% P188, 0.30% Pemulen™TR-1(TR-1), 4.0% mannitol, and 0.08% Tri(hydroxymethyl)aminomethane(Tris).Sterilization was performed at a temperature of 121℃ for a duration of 20 min. Experimental results showed that TP-gel had good safety profile and remained on the ocular surface for approximately (65.83 ± 8.79) minutes, which is four times longer than eye drops. The expression levels of IL-13, IL-17, and OVA-IgE in mouse ocular tissues with allergic conjunctivitis treated with TP-gel were significantly reduced. This suggests that TP-gel has the potential to be an effective treatment method for allergic conjunctivitis.

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2022-11-29 | A recombinant Artemisia vulgaris pollen adjuvanted Art v 1 protein-based vaccine treats allergic rhinitis and bronchial asthma using pre- and co-seasonal ultrashort immunotherapy regimens in sensitized mice.

Allergic rhinitis is an important risk factor for bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treatment of allergic rhinitis, conjunctivitis, and asthma. A disadvantage of current ASIT methods is the length of therapy which requires numerous allergen administrations. The success of ASIT is determined by its schedule, which, depending on the vaccine and type of allergy, can be pre-seasonal (before the allergy season begins), combined pre/co-seasonal (during the allergy season) etc. The aim of the present study was to evaluate a vaccine based on recombinant Artemisia vulgaris pollen major Art v 1 protein formulated with ISA-51 adjuvant for therapy of allergic rhinitis and bronchial asthma in Artemisia-sensitized mice in an ultrashort (4 subcutaneous injections at weekly intervals) pre- and co-seasonal ASIT regimen. To simulate co-seasonal ASIT in mice, mice were regularly challenged with intranasal and nebulized Artemisia vulgaris pollen extract at the same time as receiving subcutaneous ASIT. For comparison, we used a previous Art v 1 protein vaccine formulated with SWE adjuvant, which in this study was modified by adding CpG oligonucleotide (Th1-biasing synthetic toll-like receptor 9 agonist), and a commercial vaccine containing a modified Artemisia vulgaris extract with aluminum hydroxide adjuvant. The therapeutic potential of Art v 1 based vaccine formulations with different ASIT regimens was evaluated in high and low (10 times lower) dose regimens. The ISA-51-adjuvanted vaccine formulations were the only ones among those studied in the ultrashort pre- and co-seasonal ASIT regimens to provide significant reduction in both signs of allergic rhinitis and bronchial asthma in sensitized mice (vs. positive control). In the ISA-51 adjuvanted group, immune response polarization toward Th1/Treg was observed in pre-seasonal ASIT, as reflected in a significant decrease in the serum level of total and Art v 1-specific IgE and increased ratios of allergen-specific IgG2a/IgG1 and IFN-γ/IL-4. The high dose SWE-CpG-adjuvanted vaccine had similar efficacy to the ISA-51 adjuvanted groups whereas the commercial vaccine showed significantly less effectiveness. The findings support further preclinical safety studies of the Art v 1-based vaccine formulated with ISA-51 adjuvant.

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