Pediatric blepharokeratoconjunctivitis (PBKC) is an ocular surface disease characterized by conjunctivitis and keratitis secondary to chronic inflammation of the eyelid margin1). If left untreated, it can lead to corneal opacity and irreversible visual impairment, making early recognition and treatment extremely important1).
This disease was previously known by several names, including staphylococcal blepharokeratitis, phlyctenular keratoconjunctivitis, and childhood rosacea1). Recently, a unified definition and diagnostic criteria have been proposed by an expert panel1). Since meibomianitis is universally present, the term meibomian gland-associated keratoconjunctivitis is also used.
Onset typically occurs between 6 months of age and adolescence, with a bimodal pattern showing an initial peak at 4–5 years and a second peak during adolescence1). Approximately 15% of patients referred to corneal specialty clinics are diagnosed with PBKC1). Children of South Asian and Middle Eastern descent are more likely to have severe disease, and a US study found that the odds of developing PBKC were twice as high in Asian and Hispanic children compared to White children1).
In adults, BKC is usually described in association with rosacea acne, but in children, corneal involvement is more frequent and tends to be more severe.
The main symptoms are hyperemia, irritation, itching, tearing, blurred vision, and photophobia 1). These symptoms are nonspecific, so they are easily overlooked in children 1). Patients often present with recurrent chalazia or hordeola. Cases with corneal involvement may exhibit decreased visual acuity.
Anterior Blepharitis
Eyelid margin findings: Scales, crusts, and erythema on the anterior eyelid margin are characteristic 1). Collarettes form at the base of the eyelashes.
Telangiectasia: Accompanied by telangiectasia of the eyelid margin. Long-standing cases may lead to thickening and wavy deformity of the eyelid margin 1).
Posterior Blepharitis (MGD)
Meibomian gland changes: Obstruction and elevation of the gland openings are observed 1). Expressing the secretions reveals turbid, viscous discharge.
Posterior eyelid margin: Telangiectasia and scarring are seen. Chalazia can be both a cause and a consequence of MGD.
Corneal and Conjunctival Findings
Conjunctiva: Hyperemia, conjunctival edema, and phlyctenules (nodular inflammatory reactions) are observed 1).
Cornea: Superficial punctate keratitis, marginal infiltrates, phlyctenules, neovascularization, and pannus formation may occur 1). Corneal scarring typically occurs in the inferior and peripheral areas, but in severe cases it can involve the central cornea 1). Corneal perforation is rare but has been reported.
Cutaneous manifestations of rosacea (facial erythema, telangiectasia, papules, pustules) are present in 20–50% of patients with PBKC.
Pediatric BKC more frequently involves corneal lesions and tends to be more severe compared to adult BKC. This is thought to be due to an excessive immune response from the immature adaptive immune system in children to bacterial antigens. Additionally, corneal opacities during the critical period of visual development in children pose a risk of amblyopia, requiring amblyopia management 1). Adult BKC is usually described in association with rosacea.
The pathogenesis of PBKC is multifactorial, involving meibomian gland dysfunction (MGD), staphylococcal blepharitis, abnormal bacterial colonization, immune dysregulation, and angiogenesis 1).
In MGD, hyperkeratinization of meibomian gland ducts, gland atrophy, and qualitative changes in secretions occur, leading to dry eye and chronic inflammation of the eyelid margin 1). In staphylococcal blepharitis, organisms such as Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, and Corynebacterium stimulate the release of inflammatory cytokines including TNF-α, IL-1, IL-6, and IL-8, and activate the TLR-2 pathway 1). Bacterial lipases release free fatty acids, destabilizing the tear film 1).
Demodex may also contribute to PBKC through direct damage to hair follicles and alterations in the bacterial flora 1). It has been reported that eyelid margin inflammation and MGD are more pronounced in Demodex-positive patients compared to Demodex-negative patients 1).
Risk factors include poor hygiene, dietary and environmental factors, Demodex infestation, atopic predisposition, and seborrheic dermatitis 1). Risk factors for corneal lesions, an indicator of severity, include female sex, asymmetry, diagnosis at an older age, and the presence of photophobia.
Involvement has been suggested 1). Demodex is an ectoparasite that infests hair follicles and sebaceous glands, and may promote ocular surface inflammation through direct tissue damage and changes in the bacterial flora 1). It has been reported that even in children, Demodex-positive cases have more severe eyelid margin inflammation and MGD 1). Tea tree oil derivatives and ivermectin are used for treatment.
The diagnosis of PBKC is primarily based on clinical findings 1). Recently, a unified diagnostic criteria has been established by an expert panel, requiring at least one symptom or sign from each anatomical region: eyelids, conjunctiva, and cornea 1).
History taking should confirm duration, recurrence, and whether it is bilateral or unilateral. Past medical history (atopy, rosacea, recurrent chalazia) and family history are also important. Physical examination includes skin examination for signs of rosacea.
Slit-lamp microscopy evaluates the anterior eyelid margin (scales, collarettes), posterior eyelid margin (MGD findings), meibomian gland secretions, and conjunctiva (phlyctenules, hyperemia) 1). Tear film breakup time (TBUT) measurement with fluorescein staining and assessment of corneal epithelial damage are performed.
Infrared meibography is useful for evaluating meibomian gland structure in children, including infants. In older children, the Schirmer test can also be used to assess secondary dry eye.
The most important differential diagnoses are vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). VKC has onset in early childhood, tends to resolve spontaneously, and affects the upper tarsal conjunctiva. AKC is more chronic and affects the lower tarsal conjunctiva. Herpes simplex keratitis is differentiated by unilateral keratoconjunctivitis, decreased corneal sensation, and dendritic ulcers.
Refraction testing under cycloplegia is essential for evaluating secondary refractive changes and amblyopia, and should be performed regularly.
The treatment goals for PBKC are: (1) control of inflammation of the eyelid margin and ocular surface, (2) suppression of abnormal bacterial colonization, (3) prevention and recovery of corneal damage, and (4) symptom relief 1). Multidisciplinary treatment is essential.
Improvement of MGD is the first step in treatment, and lid hygiene including warm compresses, eyelid massage, and eyelid cleansing is fundamental 1). After warm compresses using a warm towel or microwaveable heat pack, perform vertical massage with a cotton swab or finger to express meibum 1). Due to the chronic nature of PBKC, lid hygiene should be continued indefinitely 1).
| Classification | Drug | Dosage |
|---|---|---|
| Topical antibiotic | Erythromycin ointment 1) | 1-2 times daily |
| Topical antibiotic | Azithromycin eye drops 1) | 2 times daily |
| Topical steroids | Prednisolone1) | 4 times daily in acute phase |
| Low-potency steroids | Loteprednol1)2) | For long-term management |
| Immunomodulators | Cyclosporine A1) | Twice daily or more |
Systemic antibiotics
Macrolides: Can be used in children of all ages and are the first choice for those under 8 years old1). Erythromycin is administered at 500–660 mg/day in 2–3 divided doses for 7–12 months1). Azithromycin is given at 5–10 mg/kg/day for 4–6 weeks and is superior in terms of tissue penetration and half-life1).
Tetracyclines: Due to the risk of tooth discoloration, use is limited to patients aged 9–12 years or older after completion of dental development1). Doxycycline is administered at 50–100 mg once or twice daily1). It has low calcium-binding affinity and is considered to have the lowest risk of tooth discoloration among tetracyclines1).
Steroid combinations and immunomodulators
LE/T combination: Loteprednol 0.5%/tobramycin 0.3% combination shows comparable efficacy to dexamethasone/tobramycin combination, with a significantly lower risk of intraocular pressure elevation2). Its usefulness in treating adult BKC has been established2).
Cyclosporine A: At concentrations of 0.05–2%, it is effective in controlling ocular surface inflammation and inducing regression of corneal neovascularization1). It is used as a long-term management drug to prevent relapse during steroid withdrawal1). Tacrolimus 0.03% has also been reported to be effective1).
As adjunctive therapy, tear supplementation with preservative-free artificial tears and intake of omega-3 fatty acids, particularly flaxseed oil, are recommended 1). Monitoring and treatment of amblyopia (cycloplegic refraction, glasses, occlusion therapy) are also important pillars of management 1).
In children under 8 years of age, macrolide antibiotics are the first choice 1). Erythromycin (10–40 mg/kg/day, or 500–660 mg/day in 2–3 divided doses) or azithromycin (5–10 mg/kg/day) are used 1). Azithromycin has superior bioavailability and half-life and is now preferred over erythromycin 1). Tetracyclines should be used only after completion of dentition, at least at 9–12 years of age, due to the risk of tooth discoloration 1).
The pathogenesis of PBKC involves a complex interaction of MGD, bacterial blepharitis, immune dysregulation, and angiogenesis 1).
In MGD, ductal obstruction occurs due to hyperkeratinization of the ductal epithelium and increased viscosity of meibum, leading to gland atrophy and decreased secretion 1). Deficiency of the tear lipid layer causes evaporative dry eye and ocular surface epithelial damage 1).
In bacterial blepharitis, C. acnes, Staphylococcus aureus, Staphylococcus epidermidis, and Corynebacterium colonize the ocular surface 1). These bacteria promote release of inflammatory mediators such as TNF-α, IL-1, IL-6, IL-8, and MMP-9, and activate the TLR-2 pathway 1). Bacterial lipases generate free fatty acids, which contribute to tear film instability 1).
Furthermore, type IV delayed-type hypersensitivity to bacterial cell wall antigens (protein A, teichoic acid) and direct tissue damage from staphylococcal exotoxins (α, β, γ hemolysins) are also involved in the pathogenesis. In children, the adaptive immune response to bacterial antigens is immature and prone to overreaction, which is considered one reason why corneal lesions occur more easily than in adults.
Demodex is an ectoparasite that infests hair follicles and sebaceous glands. In addition to direct tissue damage, it can cause bacterial dysbiosis and exacerbate ocular surface inflammation 1). If the cumulative effects of these inflammatory mechanisms are not properly managed, they can lead to vision-threatening corneal scarring 1).
Establishment of New Diagnostic Criteria: In 2024, a unified definition and diagnostic criteria for PBKC were developed by an expert panel 1). The criteria require symptoms or signs from each of the eyelid, conjunctiva, and cornea areas, and are expected to standardize diagnosis 1).
Lotilaner Ophthalmic Solution: It is attracting attention as the first FDA-approved treatment for Demodex blepharitis, but clinical trials in children have not yet been conducted 1). Results from future pediatric trials are awaited.
IPL Therapy: The efficacy of IPL therapy for MGD and BKC in adults has been reported 1). In children, preliminary reports suggest safety and efficacy for chalazion treatment and moderate to severe blepharitis 1).
New Treatment for Corneal Scarring: Topical losartan, an angiotensin II receptor antagonist, is being studied as a new candidate for corneal scar treatment 1). In a rabbit model, it inhibited myofibroblast activity and suppressed corneal scarring 1). It is expected to be applied to long-term treatment of central corneal scars remaining after PBKC treatment.
Gut-Eye Microbiome: The relationship between gut microbiota and ophthalmic diseases is attracting attention, and the existence of a gut-eye microbiota axis has been suggested 1). Although a direct link with PBKC has not been established, it is a promising area for future research 1).
Wang et al. stated, “The management of PBKC is multidimensional, encompassing lid hygiene, topical antimicrobial and anti-inflammatory treatment, systemic treatment for severe cases, dietary therapy, and amblyopia management, often requiring multidisciplinary care” 1).
IPL therapy is becoming established as effective for MGD and BKC in adults, but its application in children is still limited 1). There are reports that IPL was superior to warm compresses for pediatric chalazion treatment and that it suggests safety for moderate to severe pediatric blepharitis 1). However, sufficient clinical data have not accumulated, and results from future large-scale studies are needed.
