Where eye meets body part 1: uniting allergy pathways in ocular and nasal disease – IgE on the offense

Abstract

Purpose of review

This review explores the shared immunologic mechanisms and clinical distinctions between seasonal and perennial allergic rhinitis (SAR, PAR) and their ocular counterparts, seasonal and perennial allergic conjunctivitis (SAC, PAC). These IgE-mediated diseases often coexist, reflecting overlapping triggers, mast cell activation, and mucosal immune responses. By comparing their epidemiology, pathophysiology, genetics, and treatments, this review highlights how nasal and ocular allergic pathways intersect and diverge.

Recent findings

SAC and SAR frequently co-occur, with up to 71% of SAR patients reporting conjunctival symptoms and 75% of SAC patients experiencing rhinitis; in children, 42% with allergic rhinitis also have PAC. Recent studies suggest possible shared genetic and metabolic contributors across these conditions. Therapeutically, oral and intranasal antihistamines remain a mainstay for SAR, while combination intranasal corticosteroid-antihistamine regimens offer enhanced control in PAR. Topical dual-action antihistamine-mast cell stabilizers are commonly used in SAC and serve as first-line therapy for PAC. Novel ocular delivery systems, such as dexamethasone intracanalicular inserts, show promise for PAC.

Summary

These findings emphasize the overlap in episodic and chronic nasal and ocular allergies, with shared mechanisms, genetics, and treatment approaches, yet with site-specific nuances. Ongoing research into genetic and therapeutic differentiation remains crucial to advancing personalized allergy care.

INTRODUCTION

Seasonal and perennial allergic rhinitis (SAR, PAR) and their ocular counterparts, seasonal and perennial allergic conjunctivitis (SAC, PAC), represent some of the most prevalent IgE-mediated diseases worldwide. These conditions often coexist in affected individuals, underscoring a shared pathophysiologic foundation centered on mast cell activation and Type I hypersensitivity. Despite overlapping mechanisms, rhinitis and conjunctivitis differ in their clinical course, immune profiles, environmental triggers, and treatment approaches, with distinctions both between nasal and ocular sites and between seasonal and perennial forms. This review examines the clinical and immunological parallels and distinctions between SAR/SAC and PAR/PAC to clarify how nasal and ocular allergic pathways intersect and diverge.

HOW DOES SEASONAL ALLERGIC CONJUNCTIVITIS RELATE TO SEASONAL ALLERGIC RHINITIS?

Epidemiology of seasonal allergic rhinitis and seasonal allergic conjunctivitis

Allergic rhinitis is a prevalent disease affecting approximately 15% of the US population, roughly 50 million individuals. More broadly, it is estimated that 400–500 million people worldwide experience the condition [1^▪]. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%) [2^▪]. SAC, an inflammation of the conjunctiva triggered by airborne allergens, presents with ocular itching, redness, and tearing, and occurs in 6–30% of the general population, and up to 30% of children (Fig. 1) [3]. SAR and SAC frequently overlap, with allergic conjunctivitis occurring in 30–71% of individuals with allergic rhinitis, and allergic rhinitis present in approximately 75% of those with SAC [3,4^▪]. A nationwide patient and provider survey highlighted that both nasal and ocular symptoms significantly affect quality of life, with itchy eyes and nasal congestion rated as equally bothersome and 29% of respondents noting a major impact on daily function [5]. This overlap is further supported by the NHANES III data, which found that approximately 30% of individuals reported both ocular and nasal symptoms [6].

FIGURE 1.

Bulbar hyperemia and chemosis in a patient with seasonal allergic conjunctivitis. Photograph demonstrating bulbar conjunctival hyperemia and vascular engorgement, in a patient with SAC. Similar findings can be seen in individuals with perennial allergic conjunctivitis.

Prevalence of both conditions is rising, potentially due to climate change and increasing levels of airborne pollutants, which may affect pollen distribution and allergenicity, leading to longer allergen seasons [7,8]. Supporting this, the average annual total of daily counted airborne pollen across contiguous United States has increased by 46% from the 1990s to 2010 [9].

Shared and disparate pathophysiological mechanisms

Both SAR and SAC are characterized by IgE-mediated Type I reactions [10]. Upon re-exposure, IgE crosslinking on mast cells triggers the release of histamine and other mediators, producing nasal and ocular symptoms [11,12]. Studies have shown increased mast cell density in both nasal epithelial and lamina bulbar conjunctival tissues during allergen exposure [13,14].

Although SAR and SAC share a common mast cell–mediated mechanism, it remains unclear whether the circulation of other immune cells follows a similar pattern in both conditions. The degree to which systemic immune profiles have been characterized differs between SAR and SAC, with available findings summarized in Table 1 [15,16]. While SAR data is more available, further research is needed to characterize blood levels of immune mediators in SAC to better define systemic immune involvement.

Table 1.

Comparative immunologic and clinical features of seasonal and perennial allergic rhinitis and conjunctivitis

Aspect	Seasonal allergic rhinitis (SAR)	Seasonal allergic conjunctivitis (SAC)	Perennial allergic rhinitis (PAR)	Perennial allergic conjunctivitis (PAC)
Chronicity	Episodic	Episodic	Year-round	Year-round
Triggers	Outdoor airborne allergens (pollen)	Outdoor airborne allergens (pollen)	Continuous exposure to indoor allergens (dust mites, animal dander, mold spores)	Continuous exposure to indoor allergens (dust mites, animal dander, mold spores)
Symptoms/Signs	Sneezing, nasal congestion, itching, rhinorrhea	Ocular itching, redness, tearing, papillary conjunctivitis	Persistent nasal congestion, sneezing	Chronic ocular redness, tearing, mucinous discharge, papillary conjunctivitis
Systemic immune response	Elevated eosinophils, neutrophils, monocytes, and CD8+ T-lymphocytes in blood during allergen season	Elevated serum IgE and reduced plasma Vitamin D levels; further research needed to better define systemic immune involvement	Persistent eosinophils, neutrophils, macrophages in blood	Limited systemic studies
Immunological markers in secretions	Elevated histamine, tryptase, eosinophils, and Th2 cytokines (IL-4, IL-5, IL-13) in nasal secretions; increased substance P	Elevated histamine, tryptase, and Th2 cytokines (IL-4, IL-5, IL-13)	Increased IL-5 and IL-13 in nasal secretions; decreased IL-2; increased substance P	Imbalance in tear cytokines (low IL-10, high tumor necrosis factor-α); elevated Th2/Th17 cytokines (IL-5, IL-13, IL-17F) and increased substance P in tears
Immunological mechanism	Type 1 hypersensitivity reaction; IgE-mediated mast cell activation	Type 1 hypersensitivity reaction; IgE-mediated mast cell activation	Type 1 hypersensitivity reaction; persistent low-level IgE-mediated mast cell activation and chronic Th2-driven inflammation with recruitment of eosinophils, basophils, and T-lymphocytes into nasal mucosal tissue	Type 1 hypersensitivity reaction; persistent low-level IgE-mediated mast cell activation and chronic Th2-driven inflammation with recruitment of eosinophils, basophils, and T-lymphocytes into ocular mucosal tissue
Local immune response	Elevated mast cells in nasal epithelium during allergen season; increased expression of Th2 marker genes (GATA3, IL-5) and Th17 marker genes (IL-17F, RORA) in nasal mucosal CD4+ T-lymphocytes after allergen exposure; unmyelinated C fibers in nasal mucosa contributing to histaminergic itch	Increased mast cell density in the lamina propria bulbar conjunctiva; higher conjunctival CD4+ Th17 and Th22 cells transitioning out of allergen season; unmyelinated C fibers on ocular surface contributing to histaminergic itch	Increased CD3+ T-lymphocytes, activated eosinophils, and CD68+ macrophages in nasal mucosa; Th2-skewed inflammation with increased IL-5 mRNA and decreased IL-2 mRNA expressing cells	Shift towards inflammatory cell populations with elevated natural killer T-lymphocytes in conjunctiva
Barrier dysfunction	Not well studied	Not well studied	Decreased trans-epithelial resistance in nasal mucosa; increased permeability; reduced expression of occludin and zonula occludens-1 (ZO-1)	Epithelial disruption in conjunctiva due to imbalance in tear cytokines; tear film instability caused by mucous overproduction; goblet cell hyperplasia in conjunctiva
Genetic/Epigenetic contributors	161 associated genes; 98 upregulated genes including FOS and JUN; 63 downregulated genes including CEBPD (modulates IL-6 and IL-10); hypermethylation of CpG sites in IFN-γ	Suggested links to chromosomes 5, 16, and 17 harboring gene clusters for IL-4, c-MAF and MIP-1α; altered levels of miR-146a and miR-181a	Not well studied; CD14–159 polymorphism may modulate severity of allergic sensitization and immune response sensitivity	Not well studied; metabolite-associated genetic variation may influence allergic conjunctivitis susceptibility
Treatment approaches	Allergen avoidance; intranasal antihistamines; intranasal corticosteroids as treatment for patients older than fifteen; oral second-generation antihistamines	Allergen avoidance; ophthalmic combination antihistamines and mast cell stabilizers; oral antihistamines for concurrent systemic symptoms; topical corticosteroids for severe cases	Allergen avoidance; intranasal corticosteroids; combination corticosteroids and antihistamines; oral second-generation antihistamines; subcutaneous immunotherapy for moderate to severe cases	Allergen avoidance; ophthalmic combination antihistamines and mast cell stabilizers; ophthalmic corticosteroids for severe cases; oral second-generation antihistamines; subcutaneous immunotherapy for moderate to severe cases

This table summarizes the shared and distinct characteristics of seasonal (SAR, SAC) and perennial (PAR, PAC) allergic rhinitis and conjunctivitis. Key aspects compared include chronicity, triggers, symptom profiles, immune mechanisms, local and systemic immune responses, barrier dysfunction, genetic contributors, and treatment strategies.

Local immune responses are central to symptom expression in both SAR and SAC, with CD4⁺ cells implicated in both conditions. Immune profiling of the nasal epithelium and conjunctiva highlights overlapping and site-specific patterns of inflammation that may account for differences in clinical presentation [17,18]. Table 1 highlights these similarities and differences in local immune profiles.

While both SAR and SAC are driven by IgE-mediated mast cell activation, local T cell involvement and broader systemic immune activation, more pronounced in SAR, may further shape disease expression. Additional studies are needed to define systemic immune profiles in SAC.

Shared and disparate functional mechanisms

In addition to mast cell activation, both SAR and SAC involve neurogenic inflammation. Sensory nerves are stimulated by histamine and other mediators, contributing to symptoms such as sneezing and itching [19]. The levels of substance P (a neuropeptide that plays a crucial role in neurogenic inflammation) were found to be positively correlated with tearing after allergic challenge and with ocular itchiness following histamine nasal challenge [20]. The involvement of neurogenic pathways in allergic responses extends beyond substance P, with unmyelinated C fibers in the nasal mucosa and ocular surface also contributing to histaminergic itch and sensation in both SAR and SAC [19]. Together, these mechanisms emphasize the important role of IgE-mediated mast cell activation and neurogenic inflammation in driving the hallmark symptoms of both SAR and SAC.

Genetic contributors of disease

Genetic contributors to SAR and SAC are not well understood. A microarray study identified 161 differentially expressed genes in SAR, including 98 upregulated genes (e.g., FOS and JUN of the AP-1 transcription complex), and 63 downregulated genes. Among these, CEBPD encodes a transcription factor that modulates IL-6 and IL-10; its downregulation may contribute to exaggerated immune responses [21]. SAC genetics are less characterized, though associations have been suggested with chromosomes 5, 16, and 17, which harbor gene clusters for IL-4, c-MAF, and MIP-1a, respectively [22]. The c-MAF gene helps regulate immune responses, particularly in allergic diseases, while MIP-1a encodes a chemokine involved in mast cell and eosinophil recruitment [23,24].

Genetic predisposition to pollen reactivity may also play a role in SAR and SAC. A genome-wide scan linked reactivity to seasonal pollens with loci on chromosomes 13q34, 20p12, and 21q21 in families with asthma, using skin prick tests as phenotype. Logarithm of the odds (LOD) scores of 1.24, 2.39, and 2.58, respectively (where > 1.18 corresponds to a nominal P < 0.01) indicated linkage, with 21q21 containing ADAM33, a gene previously implicated in asthma and allergic inflammation, suggesting a possible shared genetic susceptibility for pollen-induced allergic diseases [25,26^▪].

In addition to genetic predisposition, epigenetic mechanisms, such as DNA methylation, histone modifications, and microRNAs, have been increasingly implicated in allergic disease. In allergic rhinitis, hypermethylation of CpG sites in the IFN-γ gene promoter regions is correlated with reduced IFN-γ expression in CD4⁺ T cells, contributing to Th2 polarization [27]. In allergic conjunctivitis, while specific epigenetic mechanisms remain undefined, altered levels of miR-146a and miR-181a, may influence immune regulation and inflammatory responses [27]. These findings highlight that epigenetic dysregulation may contribute to immune dysfunction across allergic diseases, warranting further investigation in ocular-specific contexts.

Shared and disparate treatment approaches

Environmental allergen avoidance is advised as a first-line strategy in SAR and SAC, though effectiveness is limited by widespread allergen exposure. Antihistamines and corticosteroids are mainstays of treatment, with administration tailored by site.

For SAR, second-generation oral antihistamines, like cetirizine, are preferred for their rapid onset and minimal sedation [28]. In SAC, oral antihistamines are reserved for patients with concurrent systemic symptoms, while ophthalmic formulations offer more targeted, faster relief with fewer side effects [29].

Both conditions benefit from local delivery. Intranasal antihistamines, like olopatadine, are guideline-recommended initial therapy for SAR, while ophthalmic olopatadine is effective in relieving SAC symptoms [30,31]. Intranasal corticosteroids (e.g., mometasone, fluticasone) are first-line for moderate-to-severe SAR in patients aged at least 15 years [32]. In contrast, topical corticosteroids such as loteprednol or fluorometholone are reserved for severe SAC due to the risk of ocular side effects with prolonged use, including elevated intraocular pressure, infection susceptibility, and cataract [33].

Mast cell stabilizers are rarely used in SAR but are more common in SAC, often combined with antihistamines. Cromolyn sodium is limited by slow onset and frequent dosing requirements in SAR, but shows efficacy for SAC [34].

Although most patients respond well to standard therapies, a subset exhibits treatment resistance [35]. These refractory cases are not well quantified but highlight the need for further study into alternative strategies. Treatment similarities and contrasts between SAR and SAC are summarized in Table 1.

Conclusions

While SAR and SAC share IgE-mediated mechanisms, and seasonal, episodic triggers, they differ in local immune activity and preferred treatment routes. Table 1 showcases key similarities and differences in immune profiles, genetic contributors, and management considerations that inform more personalized approaches.

HOW DOES PERENNIAL ALLERGIC CONJUNCTIVITIS RELATE TO PERENNIAL ALLERGIC RHINITIS?

Epidemiology of perennial allergic rhinitis and perennial allergic conjunctivitis

PAR is a chronic, nonseasonal allergic condition triggered by indoor allergens such as house dust mites, animal dander, and mold spores. PAR affects a significant portion of the population, with global prevalence ranging from 10 to 30% [36^▪]. It has been shown that urban populations and racial minorities are disproportionately affected by PAR [37]. Among elderly populations, PAR remains a common condition, with a prevalence of 17.1% in elderly patients in a study conducted in Poland [37].

PAC, a chronic form of allergic conjunctivitis that persists year-round, is frequently associated with PAR, as both conditions are driven by mostly similar perennial allergens [38,39^▪]. In the general population, allergic conjunctivitis, including both seasonal and perennial forms, affects between 6% and 30% of individuals [3]. PAC accounts for approximately 10–18% of all cases of allergic conjunctivitis, with prevalence increasing with age; the mean age of affected individuals is 56.1 years [3,6]. In pediatric populations, 42% of children with allergic rhinitis also experience PAC, reinforcing the strong link between the two conditions [39^▪].

PAR and PAC do not have a significant sex predilection, though some studies suggest a slight female predominance [40]. While no studies have directly examined whether patients with PAR or PAC are more likely to also experience SAR or SAC, it is plausible given their allergic profiles and the possibility of reacting to multiple allergens (seasonal and perennial).

Shared and disparate pathophysiological mechanisms

Unlike SAR and SAC, which are triggered by seasonal outdoor allergens such as pollen from trees, grasses, and weeds, PAR and PAC are primarily triggered by continuous exposure to indoor allergens such as dust mites, pet dander, and molds. This year-round allergen presence leads to persistent low-level mast cell activation and chronic Th2-driven inflammation, promoting the sustained recruitment of eosinophils, basophils, and T cells into the affected mucosal tissues [41,42].

Both PAR and PAC exhibit chronic reactive immune environments, with Th2-skewed inflammation and site-specific immune cell profiles in nasal and conjunctival tissues [18,43]. These overlapping but distinct findings are detailed in Table 1.

Although the primary distinction between PAR and PAC lies in their affected tissues, their shared chronic allergic mechanisms suggest potential overlap. In support of this, a study involving PAC patients found that 45 nasal allergen challenges elicited positive nasal responses, of which 19 were accompanied by significant conjunctival reactions, indicating a link between nasal allergy and ocular symptoms in PAC [44].

Shared and disparate functional mechanisms

The chronic inflammation underlying PAR and PAC leads to sustained alterations in mucosal function, including barrier disruption, secretory hyperactivity, and heightened sensory responsiveness, which together drive the persistent symptoms characteristic of both conditions (Fig. 2). In patients with house dust mite–induced PAR, nasal mucosal transtissue resistance was significantly lower compared to controls, as assessed by nasal biopsy. This was accompanied by increased permeability to fluorescein isothiocyanate–dextran 4 kDa, a marker of paracellular leakiness, and reduced mRNA expression of occludin and zona occluden-1 (ZO-1), as also observed in atopic keratoconjunctivitis, another chronic allergic eye disease. Symptom severity negatively correlated with tissue resistance, highlighting the role of barrier dysfunction in potentially contributing to persistent nasal symptoms [45].

FIGURE 2.

Papillary conjunctivitis and mucous accumulation in perennial allergic conjunctivitis. Photograph showing papillary conjunctivitis and a mucinous discharge in an individual with perennial allergic conjunctivitis.

While epithelial thickness has not been quantified in PAC, chronic inflammation has been shown to induce epithelial remodeling and barrier disruption, contributing to persistent ocular surface symptoms [46]. Tear samples from PAC patients show a significant imbalance in anti and pro-inflammatory cytokines, with IL-10 levels 2.8 times lower than tumor necrosis factor-alpha (TNF-α) levels compared to healthy controls, highlighting a persistent inflammatory. TNF-α promotes epithelial disruption and immune activation in allergic diseases [47]. Another key aspect of the remodeling seen in PAC is goblet cell hyperplasia and mucin overproduction driven by IL-4 and IL-13. An in-vitro study using primary rat conjunctival goblet cells showed that IL13 increased mucin secretion by 5.15 ± 3.49-fold over basal levels, while both IL-4 and IL-13 stimulated goblet cell proliferation, suggesting that the elevated levels of these cytokines in PAC may drive goblet cell hyperplasia and mucous overproduction, contributing to tear film instability and chronic ocular surface inflammation [48]. These findings mirror nasal epithelial changes in PAR, where tight junction protein loss and increased permeability similarly reflect barrier compromise. However, goblet cell hyperplasia and mucin overproduction appear to be more prominent in PAC. Notably, recent research in allergic rhinitis suggest that goblet cell secretion may be modulated by a neuroimmune axis, hinting at parallel neuron-goblet cell interactions [49].

In a similar fashion to their seasonal counterparts, neurogenic inflammation likely plays a crucial role in PAR and PAC. In PAR, neuropeptides and cytokines released during allergic inflammation have been shown to sensitize sensory nerves, resulting in sensory nerve sensitization and heightened nasal responses [50]. In patients with PAR, nasal allergen provocation resulted in significantly elevated concentrations of substance P in nasal lavage fluid within 15 min, supporting the role of neuropeptides in sensitizing sensory nerves and contributing to heightened nasal responses [51]. In PAC, neuropeptides such as nerve growth factor (NGF) and substance P have been found to be upregulated during allergic reactions and have been shown in experimental systems to increase sensory nerve excitability and promote neurogenic inflammation. For example, mast cell activation in allergic tissue can lead to the release of NGF, which is retrogradely transported to neuronal cell bodies and induces long-term changes in gene expression, including the upregulation of neuropeptides [19]. While both PAR and PAC involve neuropeptide-driven sensory sensitization, data in PAC remains more limited. Nonetheless, the presence of shared mediators such as substance P in both conditions points to a conserved neuroimmune axis contributing to symptom persistence.

Genetic contributors of disease

The genetic landscape of PAR and PAC remains largely unexplored, with most studies focusing on seasonal or generalized allergic conditions. One study examined CD14–159C/T promoter polymorphisms in 151 Korean children with PAR. While genotype frequencies (CC, CT, TT) did not differ significantly between cases and controls, the CC genotype was associated with higher total serum IgE levels and a greater mean number of positive skin prick test. These findings suggest that the polymorphism may not affect disease risk but may influence the severity of allergic sensitization and immune reactivity [52].

A broader Mendelian randomization study of 20 958 AC cases identified eight blood metabolites, such as palmitate and carnitine, with significant genetic heritability and causal links to AC. While these findings suggest a role for metabolite-associated genetic variation in allergic conjunctivitis susceptibility, they were limited by lack of allergic conjunctivitis subtype classification [53^▪▪]. Together, these studies underscore the need for further research into genetic and epigenetic contributors to PAR and PAC.

Shared and disparate treatment approaches

Allergen avoidance measures, including dust mite control, pet exposure reduction, and mold remediation, form the foundation of initial management for PAR and PAC, though complete elimination of perennial allergens is often difficult. The clinical management of PAR is highly individualized, and although current guidelines do not provide treatment algorithms specific to PAR, they recommend intranasal corticosteroids as first-line monotherapy for patients with persistent allergic rhinitis [54]. This differs from SAR, where antihistamines are typically used first, as corticosteroids provide better control of persistent low-grade inflammation characteristic of PAR [32]. Combinations of corticosteroids and antihistamines have also shown efficacy in managing nasal symptoms in PAR [55^▪▪].

Although a commonly used therapy for SAR, second-generation oral antihistamines are considered a second-line treatment for mild, year-long symptoms in PAR, and are commonly adjunctive to corticosteroid treatment [2^▪,56]. Second-generation oral antihistamines are more frequently used in PAC compared to other forms of conjunctivitis, although it is not clear if their use targets PAC or comorbid PAR [57]. Further studies are needed to clarify their role in chronic PAC management.

Similar to SAC, combination topical antihistamines and mast cell stabilizers are first line therapies for PAC and have been shown to be effective treatments for reducing ocular symptoms [58,59]. Monotherapy is used less frequently in the treatment of PAC [60]. Similar to SAC, topical corticosteroids are reserved for more severe cases of PAC to control acute flare-ups and are not recommended for long-term use [61].

Subcutaneous immunotherapy (SCIT) is considered in both allergic rhinitis and allergic conjunctivitis when symptoms persist despite standard pharmacological therapy, with potential to modify disease course [54,62]. Immunotherapy has similar impacts on allergic rhinitis and allergic conjunctivitis, working by inducing tolerance through repeated exposure to specific allergens, leading to increased T and B cell activity, reduced IgE production, and increased allergen-neutralizing IgG antibodies. Over time, this immune modulation reduces allergic symptoms and can also help prevent development of new sensitizations. A newer development in PAC is the 0.4 mg dexamethasone intracanalicular insert (Dextenza) which offers sustained corticosteroid delivery and showed higher patient preference and greater symptom improvement than loteprednol or olopatadine [63^▪▪].

Data on treatment-resistant PAR and PAC remain limited, though refractory cases are reported clinically, underscoring the need for further study of chronic allergic persistence.

Conclusion

PAR and PAC are chronic, nonseasonal allergic conditions driven by shared immunologic pathways, including persistent mast cell activation, and Th2-skewed inflammation. Despite affecting different mucosal surfaces, both diseases exhibit overlapping pathophysiology and functional consequences. Table 1 summarizes their similarities and differences in immune response, genetic contributors, and treatment approaches.

CONCLUSION

Seasonal and perennial allergic rhinitis and conjunctivitis exemplify how shared immunologic mechanisms can manifest across distinct mucosal surfaces (Fig. 3). While their overlapping features support unified therapeutic strategies, differences in chronicity, tissue-specific inflammation, and patient experience demand tailored approaches to care. Advances in our understanding of barrier dysfunction and neuroimmune signaling have improved insight into disease mechanisms, although their impact on current treatment remains limited, particularly in ocular allergy. In parallel, the genetic underpinnings of these conditions, especially in ocular manifestations, remain incompletely defined. Continued investigation into the unique and shared pathways, including deeper exploration of immunogenetic drivers, will be essential to improve diagnosis, guide personalized therapy, and ultimately reduce the burden of allergic disease across both ocular and respiratory domains.

FIGURE 3.

IgE-mediated pathways in seasonal and perennial nasal and ocular allergy. Diagram highlighting shared IgE-mediated mast cell activation and key immunologic distinctions between seasonal (left) and perennial (right) allergic rhinitis and conjunctivitis. Both forms involve histamine-driven inflammation, while differences in immune cell populations, epithelial barrier changes, and mucosal responses contribute to symptom patterns and chronicity. Created in BioRender. Borges, S. (2025) https://BioRender.com/6h3bzgy.

KEY POINTS.

• Seasonal and perennial allergic rhinitis and conjunctivitis share IgE-mediated mast cell activation but differ in chronicity, immune profiles, and tissue responses.

• Neurogenic inflammation and barrier dysfunction contribute to persistent symptoms across both nasal and ocular allergic diseases.

• Shared and disparate treatment approaches, including differences in delivery methods, reflect the overlapping yet distinct clinical presentations of nasal and ocular allergy.