Allergic conjunctival disease (ACD) is defined as “an inflammatory disease of the conjunctiva primarily involving a type I allergic reaction, accompanied by subjective symptoms and objective findings triggered by an antigen” 1). When the causative antigen enters the conjunctival sac and dissolves in tears, it invades the conjunctival tissue, binds to IgE, and stimulates mast cells via receptors. As a result, chemical mediators including histamine are released, acting on blood vessels and sensory nerve endings to induce itching, conjunctival hyperemia, and edema. Simply having an allergic predisposition does not lead to a diagnosis of ACD; it is diagnosed only when both subjective symptoms and inflammatory changes in the conjunctiva are present 1).
The prevalence in children is approximately 20%, and in recent years it has been increasing and occurring at younger ages. According to a 2017 nationwide epidemiological survey (Japan Ocular Allergy Research Society), the overall prevalence of ACD reached 48.7%, a significant increase from the estimated 15–20% in the 1993 survey 1). The prevalence by disease type was reported as: SAC due to Japanese cedar and cypress 37.4%, PAC 14.0%, other SAC 8.0%, AKC 5.3%, VKC 1.2%, and GPC 0.6% 1). Overall ACD peaks in the 40s, with a smaller peak in the teens. For SAC, prevalence increases with age from childhood, and regionally it correlates with Japanese cedar pollen dispersal, tending to be higher in the Tokyo metropolitan area and Chubu region 1).
ACD is classified into four types. The presence or absence of proliferative changes, atopic dermatitis, and mechanical irritation are the axes of classification.
Seasonal allergic conjunctivitis (SAC) is typified by hay fever. It occurs in conjunction with the pollen dispersal season of Japanese cedar and cypress, and the complication rate of rhinitis symptoms is high at 65–70%1). The prevalence is 37.4% for SAC due to Japanese cedar and cypress, and 8.0% for other SAC1).
Perennial allergic conjunctivitis (PAC) is characterized by persistent symptoms without seasonal variation, with house dust and mites as the main antigens. The prevalence is 14.0%1).
Vernal keratoconjunctivitis (VKC) is a proliferative ACD that commonly occurs in boys around 10 years of age, often associated with atopic dermatitis. Although its prevalence is low at 1.2%, it is a severe type that can lead to serious corneal complications such as shield ulcers1). It is subclassified into palpebral (cobblestone giant papillae), limbal (gelatinous limbal hypertrophy, Trantas dots), and mixed types.
Atopic keratoconjunctivitis (AKC) is a chronic ACD accompanied by atopic dermatitis on the face, with a prevalence of 5.3%1). It is often associated with conjunctival fibrosis, corneal neovascularization, and opacification, and may present with giant papillae during exacerbations1).
Giant papillary conjunctivitis (GPC) results from a combination of mechanical irritation (e.g., contact lenses, ocular prostheses, surgical sutures) and allergic inflammation. It is considered the most severe type, with papillae ≥1 mm in diameter, and has a prevalence of 0.6%1).
QWhat types of allergic conjunctivitis are there in children?
A
Allergic conjunctival diseases are classified into five types according to guidelines. Seasonal allergic conjunctivitis (SAC) is seasonal without proliferative changes, while perennial allergic conjunctivitis (PAC) is perennial. Severe types with proliferative changes (giant papillae, limbal hypertrophy) include vernal keratoconjunctivitis (VKC), which commonly occurs in school-aged boys. Atopic keratoconjunctivitis (AKC) is associated with facial atopic dermatitis, and giant papillary conjunctivitis (GPC) is caused by mechanical irritation from contact lenses, ocular prostheses, etc.1).
Ocular itching is the most characteristic symptom of ACD. It occurs when histamine stimulates sensory nerve endings. In children, they may not complain of “itching” but may use other expressions such as “feeling gritty” or “something wrong with my eye” 1).
Discharge: Small amount, white to translucent, stringy and viscous. It differs from bacterial discharge in that it remains white due to few neutrophils.
Foreign body sensation: Often caused by numerous conjunctival papillae touching the cornea during blinking 1).
Tearing: Reflex tearing.
Eye pain, photophobia, and decreased vision: These occur in severe cases with corneal involvement and correlate with disease severity1).
Objective Findings and Clinical Grading Criteria1)
Vernal keratoconjunctivitis (VKC) during the exacerbation phase shows cobblestone-like giant papillary hypertrophy on the upper tarsal conjunctiva. In the limbal type, limbal gelatinous elevations and Trantas dots are observed. Corneal complications are primarily caused by epithelial damage from eosinophil-derived cytotoxic substances (e.g., MBP) released from the conjunctiva. It can progress from superficial punctate keratopathy to corneal erosion, persistent corneal epithelial defect, shield ulcer, and corneal plaque 1). Shield ulcers are often accompanied by corneal plaques, are refractory, and require long-term treatment. Severe cases may lead to difficulty opening the eyelids and decreased vision. After intense limbal inflammation, pseudogerontoxon may remain 1).
It is complicated by blepharitis due to atopic dermatitis, and Hertoghe’s sign and Dennie-Morgan folds are observed. In chronic cases, conjunctival sac shortening and symblepharon occur 1). Yellowish viscous discharge may also be seen 1).
Clinical diagnosis (A only): Presence of clinical symptoms characteristic of ACD.
Clinical confirmed diagnosis (A+B): Clinical symptoms plus type I allergic predisposition (positive total IgE in tears, positive serum antigen-specific IgE, or positive skin reaction).
Definitive diagnosis (A+B+C or A+C): In addition to the above, eosinophils in conjunctival scrapings are positive.
The specificity of clinical symptoms is as follows1):
Eosinophil detection in conjunctival scrapings: Hansel or Giemsa staining; even one positive cell can confirm the diagnosis.
Total IgE antibody measurement in tears (Allerwatch®): Immunochromatography method. Reported sensitivity 73.6%, specificity 100%1).
Serum antigen-specific IgE antibody measurement: Useful for identifying the causative antigen. PAC sets (mite, house dust, Japanese cedar, cypress, orchard grass, etc.) can be used under insurance coverage1).
Conjunctival provocation test: A method to confirm the onset of conjunctivitis by instilling a known antigen solution. Not covered by insurance, and standard solutions are not commercially available1).
Viral conjunctivitis: Acute onset, often unilateral, preauricular lymphadenopathy. Differentiate with adenovirus rapid diagnostic kit.
Bacterial conjunctivitis: Mucopurulent, yellow to yellow-green discharge. No conjunctival follicles.
Chlamydial conjunctivitis: Characterized by giant follicles on the lower palpebral conjunctiva.
Conjunctival folliculosis: Common in children. Miliary translucent follicles on the lower palpebral conjunctiva, no subjective symptoms.
Dry eye: Diagnosed by shortened BUT. Often coexists with ACD.
QHow to differentiate allergic conjunctivitis from infectious conjunctivitis in children?
A
The most important differentiating points are the presence or absence of ocular itching and the nature of discharge. In allergic conjunctivitis, ocular itching is characteristic, and discharge is white to translucent, mucoid, and stringy. In bacterial conjunctivitis, mucopurulent, yellow to greenish discharge is seen, and foreign body sensation predominates over itching. Viral conjunctivitis often has acute onset, is unilateral, and is accompanied by preauricular lymphadenopathy. For confirmation, adenovirus rapid diagnostic kits or detection of eosinophils in conjunctival scrapings are useful 1).
Searching for the causative antigen and avoiding it is most important. Drug therapy is central, and the first choice for all disease types is anti-allergic eye drops 1). Depending on severity, steroid eye drops are used in combination, and for refractory severe cases (VKC, AKC), immunosuppressive eye drops are used 1).
Starting anti-allergic eye drops about 2 weeks before the predicted pollen dispersal date or when symptoms first appear can reduce symptoms during the peak dispersal period1). If nasal symptoms are severe, oral anti-allergic medications may be used in combination (however, for ACD alone, oral medications are not covered by insurance)1).
When anti-allergic eye drops are insufficient, steroid eye drops of appropriate potency are used in combination depending on severity1). For SAC/PAC, steroid eye drops are “weakly recommended” (evidence B), and for VKC, “strongly recommended” (evidence B)1).
Main steroid eye drops1):
High potency: Betamethasone sodium phosphate 0.1%, Dexamethasone 0.1%
Medium to low potency: Fluorometholone 0.02%, 0.05%, 0.1%; Dexamethasone metasulfobenzoate sodium 0.05%, 0.1%
Precautions for using steroid eye drops in children
Children are more prone to increased intraocular pressure from steroid eye drops, which can lead to acute high eye pressure 1). Regular intraocular pressure measurement (at least once a month) is necessary 1). With high-potency steroids (e.g., betamethasone), symptoms may improve, leading to self-discontinuation and a vicious cycle of worsening. Particular caution is needed from age 10 onward when eye drops are self-administered. When using oral steroids, limit to 1–2 weeks and coordinate with an internist or pediatrician 1). Subconjunctival injection of steroid suspension in children under 10 years old should be avoided 1).
Indications: Covered by insurance for VKC. Not covered for AKC, but efficacy has been reported1).
Recommendation: In guideline CQ7, it is “strongly recommended” (evidence A) for improving corneal epithelial disorders and giant papillae in VKC/AKC. It is “weakly recommended” (evidence B) over steroid eye drops 1).
Features: Effective as monotherapy even in severe steroid-resistant cases. No elevation of intraocular pressure is observed1).
Cyclosporine eye drops (Papilock Mini® 0.1%)
Dosage: Instill 3 times daily
Indications: Covered by insurance for VKC. Not covered for AKC.
Recommendation: Guideline CQ4 “weakly recommends” use for VKC. In particular, 2% formulations have been reported to have therapeutic effects equivalent to high-potency steroids 1).
Features: Can be used in combination with steroid eye drops to taper steroids. No steroid-induced intraocular pressure elevation 1).
The main side effect of both agents is stinging upon instillation. Caution is needed for herpetic keratitis and MRSA infection, especially in patients with atopic dermatitis.
Treatment is intensified and adjusted using a stepwise approach.
Mild: Anti-allergic eye drops only.
Moderate or severe: Add immunosuppressive eye drops to anti-allergic eye drops.
Severe (insufficient with two drugs): Add steroid eye drops. Consider oral steroids, subconjunctival injection, or surgical treatment depending on symptoms.
After improvement: Switch steroid eye drops to a lower potency, then taper and discontinue. Control with two drugs: anti-allergic and immunosuppressive.
Remission (proactive therapy): Gradually reduce immunosuppressive eye drops from twice daily to once daily to twice weekly, and continue maintenance dose 1).
Combination of cyclosporine and steroids for conjunctival proliferative changes is “weakly recommended” in CQ6 (evidence C). Combination of tacrolimus and steroids is also “weakly recommended” in CQ9 (evidence C) 1).
Conjunctival papillae resection: Indicated for cases resistant to drug therapy with worsening corneal epithelial disorders. The need has decreased significantly due to the widespread use of immunosuppressive eye drops. Continue immunosuppressive and anti-allergic eye drops postoperatively to prevent regrowth.
Corneal plaque removal: Perform surgical scraping. It is desirable to perform after the disease activity has subsided. Corneal plaques associated with shield ulcers tend to recur if immunosuppressive treatment is not continued after removal.
Management of shield ulcers: For shield ulcers themselves, prioritize drug therapy (intensified immunosuppressive eye drops, addition of steroids) first. In refractory cases, scraping, therapeutic soft contact lens wear, and amniotic membrane transplantation are also options1).
Cooling the eyelid skin with a cold pack (cold compress) is not immediately effective but is safe and useful. Artificial tear eye drops to dilute antigens are also recommended, and preservative-free formulations are preferred1).
Long-term management concept: Vernal keratoconjunctivitis (VKC) repeatedly exacerbates and remits throughout school age. Adjustment of eye drops according to symptom fluctuation is necessary, and proactive prevention before exacerbation prevents worsening. Most cases naturally improve after puberty, but atopic keratoconjunctivitis can persist into adulthood. In cases with atopic dermatitis, collaborate with dermatology to continue facial moisturizing and dermatitis control.
Consideration for compliance: Parental support is essential for pediatric eye drop compliance. Since stinging sensation (especially with immunosuppressive eye drops) can lead to self-discontinuation, appropriate explanation and measures are important. Explain the types and frequency of eye drops, and instruct parents on home observation points (signs of elevated intraocular pressure such as headache, rainbow-colored halos, blurred vision, etc.).
Attention to infections: When using steroids or immunosuppressants, be cautious of MRSA colonization/infection on the ocular surface, herpes induction, and Kaposi’s varicelliform eruption, especially in patients with atopic dermatitis. Adjust follow-up frequency according to steroid potency and duration, and promptly switch to antibiotics or antivirals if signs of infection appear.
QWhat is the first drug used in the treatment of vernal keratoconjunctivitis?
A
For all allergic conjunctival diseases, anti-allergic eye drops (H1 receptor antagonists such as olopatadine and epinastine, or mediator release inhibitors such as pemirolast) form the basis of treatment. For moderate to severe VKC, immunosuppressive eye drops are added, and for severe pediatric cases, tacrolimus 0.1% eye drops (Talymus®) should be considered first-line 1). Steroid eye drops are effective, but due to the high risk of elevated intraocular pressure in children, they are recommended to be added only when immunosuppressive eye drops fail to control symptoms.
QWhat should be noted when children use steroid eye drops?
A
In children, steroid eye drops can easily increase intraocular pressure and may cause acute ocular hypertension1). Intraocular pressure should be measured at least once a month. When symptoms improve with high-potency steroids, patients may discontinue use on their own, leading to a vicious cycle of repeated exacerbations. This risk is particularly high after age 10, when patients self-administer eye drops. Also be cautious of steroid-induced infections (MRSA, herpes), and always use under the supervision of an ophthalmologist.
Type I allergic reactions (IgE-mediated) are predominant. In recent years, allergic inflammation has been understood as “type 2 inflammation,” encompassing both innate and adaptive immune systems 1).
Inflammation progresses through the following steps 1):
IgE production and effector response: Th2 cells produce IL-4 (IgE class switching in B cells), IL-5 (eosinophil activation), and IL-13 (increased epithelial mucin production).
Immediate phase reaction: Re-entry of allergen → IgE cross-linking → mast cell degranulation → release of histamine, leukotrienes, and prostaglandins → redness, swelling, and itching.
Chronic inflammation (VKC/AKC): Chronic activation of lymphocytes → infiltration of eosinophils and macrophages → upregulation of Th2 cytokines and chemokines → persistent proliferative changes in fibroblasts.
Mechanism of corneal damage in vernal keratoconjunctivitis
Eosinophil-derived cytotoxic substances (such as MBP: major basic protein) released from the conjunctiva damage the corneal epithelium. It can progress from punctate superficial keratopathy to corneal erosion, shield ulcer, and corneal plaque1).
In addition to type I allergic reactions, type IV (delayed-type) hypersensitivity reactions characterized by infiltration of T cells, macrophages, and dendritic cells are also involved. Chronic eye rubbing causes mechanical damage and chronic inflammation, which together increase the risk of keratoconus. In AKC, decreased corneal sensitivity and reduced conjunctival goblet cell density have been reported, and the disease tends to follow a chronic progressive course. During use of immunosuppressive eye drops or steroids, special attention should be paid to MRSA carriage/infection and herpes induction.
Factors contributing to the recent increase in ACD prevalence include increased cedar pollen antigen levels due to air pollution (PM2.5, yellow dust, etc.), changes in pollen dispersal due to environmental changes, increased allergic predisposition due to urbanization, and decreased opportunities for infectious diseases (hygiene hypothesis) 1).
The age distribution of disease-specific prevalence (2017 survey) shows the following trends 1):
Overall ACD: most common in the 40s, with a small peak in the teens
Wu K, Yang Y. A Bibliometric Study on Research Trends and Characteristics of Pediatric Allergic Conjunctivitis. J Asthma Allergy. 2025;18:1297-1309. PMID: 41000436.
Mahoney MJ, Bekibele R, Notermann SL, Reuter TG, Borman-Shoap EC. Pediatric Conjunctivitis: A Review of Clinical Manifestations, Diagnosis, and Management. Children (Basel). 2023;10(5). PMID: 37238356.
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