Advances in the Medical Management of Pediatric Blepharokeratoconjunctivitis

Abstract

Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic inflammatory condition of the ocular surface that affects the eyelids, conjunctiva, and cornea that can lead to corneal scarring and permanent vision loss if untreated. The condition presents with diverse clinical features, necessitating a broad range of therapeutic approaches. Current management strategies include eyelid hygiene practices, topical and systemic antibiotics, and anti-inflammatory agents, often in combination for optimal outcomes. Given the expanding spectrum of medical options and the emergence of new therapeutic avenues, staying current with available treatments can be challenging. This review, based on a PubMed search using the terms pediatric blepharokeratoconjunctivitis, pediatric ocular rosacea, pediatric phlyctenular disease, pediatric phlyctenular keratoconjunctivitis, and pediatric blepharokeratitis, aims to provide ophthalmologists with a comprehensive overview of the current medical strategies. Early and multimodal therapeutic strategies that target multiple facets of eyelid margin and ocular surface inflammation, coupled with timely amblyopia treatment, is required to prevent vision loss due to PBKC.

Key Summary Points

Prompt treatment of pediatric blepharokeratoconjunctivitis (PBKC) is necessary to prevent corneal opacification and irreversible visual loss.

There are a wide range of topical and systemic anti-infective and anti-inflammatory treatment options for this disease that target different aspects of the ocular surface, such as the eyelids, conjunctiva, or cornea, and effective treatment often requires a multimodal approach.

This review paper provides a comprehensive review of current pharmaceutical and non-pharmaceutical treatment strategies for PBKC, including eyelid hygiene practices, anti-inflammatory agents, antibiotics, as well as dietary strategies and visual rehabilitation approaches to prevent visual loss in children.

Introduction

Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic inflammatory condition of the ocular surface that affects the eyelids, conjunctiva, and cornea in children and adolescents [1–14]. The disease is often underdiagnosed or misdiagnosed as a result of its insidious onset and overlap with other more common pediatric ocular surface conditions. If not treated promptly, it can result in corneal opacification and irreversible visual loss, making early recognition and treatment essential to preserving visual function during the critical period of visual development [1, 6, 15, 16]. This literature review aims to provide a comprehensive overview of the medical treatment modalities available for PBKC.

Methods

This narrative review was conducted through a structured search of the PubMed database to identify relevant peer-reviewed literature on pediatric inflammatory ocular surface diseases. The following search terms were applied individually and in combination: “pediatric blepharokeratoconjunctivitis,” “pediatric ocular rosacea,” “pediatric phlyctenular disease,” “pediatric phlyctenular keratoconjunctivitis,” and “pediatric blepharokeratitis.” Clinical studies, case series, and systematic reviews that provided information on epidemiology, pathophysiology, clinical presentation, diagnostic approaches, and treatment strategies were prioritized. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Incidence and Demographics

While the incidence and prevalence of PBKC are largely unknown, it is estimated to be the reason for referral to cornea specialists in approximately 15% of cases [1, 13, 17]. PBKC appears to exhibit a bimodal incidence, with an initial onset around 4–5 years of age followed by another peak in adolescence [18]. Previous studies have shown greater disease severity in children of South Asian and Middle Eastern descent, while others have reported greater frequency in children of Asian and Latino descent [3, 19–21]. A recent large retrospective study in the USA found that children of Asian or Latino descent demonstrated twice the odds of developing BKC compared with Caucasian children [21]. It is currently unclear what factors contribute to these potential regional differences, but risk factors and associated conditions include poor hygiene, dietary and environmental factors, infestation with Demodex mites, history of atopy, and seborrheic dermatitis [22].

Etiology and Pathogenesis

PBKC involves a multifactorial interplay between meibomian gland dysfunction (MGD), staphylococcal blepharitis, abnormal microbial colonization of the ocular surface involving Cutibacterium acnes (C. acnes) and staphylococcal species, immune dysregulation involving both the innate and adaptive immune mechanisms, and vascularization [1, 18, 22]. Although the triggers for MGD in PBKC are unclear, eyelid ductal hyperkeratinization, glandular atrophy, and changes in meibum secretion lead to dry eye and chronic inflammation of the eyelid margins and the ocular surface [22, 23]. In staphylococcal blepharitis, agents such as C. acnes, Staphylococcus aureus, Staphylococcus epidermidis, Corynebacterium species can stimulate the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukins (ILs), upregulation of the TLR-2 pathway, and release of free fatty acids through their lipases that lead to surface inflammation [13, 18, 22, 24].

Demodex, an ectoparasite that colonizes hair follicles and sebaceous glands, may also play a role in the ocular surface changes and contribute to PBKC through direct damage or bacterial dysbiosis [25, 26]. It is postulated that demodex can cause direct damage or induce bacterial dysbiosis [25], contributing to worse lid margin inflammation and meibomian gland dysfunction in demodex-infected patients compared to demodex-negative patients with PBKC [26]. The cumulative effect of these mechanisms can result in chronic ocular surface inflammation and, subsequently, vision-threatening corneal scarring if not managed appropriately.

Clinical Presentation and Diagnosis

PBKC can present with a broad spectrum of clinical manifestations, including blepharitis and external hordeola to persistent chalazia, conjunctivitis, corneal infiltrates, and neovascularization [1] (Fig. 1). It frequently presents with nonspecific symptoms such as redness, irritation, itching sensation, watering, blurry vision, and photophobia, and thus is often underdiagnosed in children [4, 6, 15, 17]. PBKC has been referred to by several different terms, including blepharokeratitis, childhood acne rosacea, and phlyctenular keratoconjunctivitis, and recently, a unified definition based on an expert panel was derived, including a set of diagnostic criteria (Fig. 2) [1, 14].

Fig. 1.

Clinical presentation of an eye with active pediatric blepharokeratoconjunctivitis with eyelid margin disease, conjunctival injection, corneal neovascularization, and central corneal opacification

Fig. 2.

Definition of pediatric blepharokeratoconjunctivitis (PBKC) [14]. *One symptom or sign must be present from each anatomical region to meet the diagnostic criteria for PBKC

Treatment of PBKC

Goals of Medical Treatment

The goals of medical treatment are to (1) control eyelid margin and ocular surface inflammation, (2) reduce abnormal bacterial colonization, (3) prevent and reverse corneal damage, and (4) alleviate symptoms. Medical treatment modalities typically target MGD, ocular surface dysbiosis, ocular surface inflammation, and associated corneal neovascularization [1, 3, 11, 17, 22, 27–35]. Figure 3 provides an overview of the targeted anatomy for different medical treatment options.

Fig. 3.

Current ocular surface-directed treatment options for pediatric blepharokeratoconjunctivitis

Medical Treatment Options

Eyelid Hygiene

Improving MGD is the first-line treatment for PBKC and involves eyelid hygiene, used for both initial control and long-term management of lid margin disease. This approach targets meibomian gland (MG) obstruction and assists with the control of ocular surface inflammation [1, 17, 18, 27, 28, 30–35]. Daily warm lid compresses and lid margin cleaning, through lid scrubs, eyelid cleansers, and wipes, assist with the melting, expression, and removal of MG secretions and debris from the lid margin. Warm compresses can be applied using either warm water-soaked towels or microwaveable moist heat packs [17]. Vigorous massage of the lids using either fingers or cotton applicators immediately following heat application allows for further expression of the meibum secretions. Treatment may be hindered by compliance issues related to the younger age of patients as well as the availability of parents/caregivers. A simplified treatment schedule involving once-daily or less frequent dosing may improve long-term compliance.

Topical Therapies

A summary of topical treatment options for PBKC is provided in Table 1.

Table 1.

Topical treatment options for the management of pediatric blepharokeratoconjunctivitis

Type	Medication	Dosing schedule	Duration
Antibiotic	Erythromycin ointment 0.5% [18, 19, 28, 40]	Once or twice daily	≥ 6 weeks
	Ciprofloxacin-HCl 3.3 mg ointment [19, 40]	Once daily	≥ 6 weeks
	Azithromycin 1.5% [2, 40]	Twice daily for 2 days and then once daily	4–8 weeks
		Twice daily	< 6 months
	Chloramphenicol 0.5% [3, 6, 8, 36]	Four times a day	4–6 weeks [3]
	Chloramphenicol 1% ointment [3, 8]	N/A	Once daily
	Ciprofloxacin 0.3% [6, 36]	N/A	N/A
	Fusidic acid [36, 49]	N/A	N/A
	Gentamicin [6, 36]	N/A	N/A
Steroids	Dexamethasone phosphate 0.1% drop [40]	Hourly – every other day	4–6 weeks
	Prednisolone 0.3–0.5% [3]	Four times a day	4–6 weeks
		Once or twice daily	2–3 months
	Loteprednol etabonate 0.2–0.5% [40]	Hourly – every other day	4–6 weeks
	Fluorometholone phosphate 0.1% [40]	Hourly – every other day	4–6 weeks
Combination antibiotic and steroid	Azithromycin 1% and dexamethasone 0.1% [41, 65, 81, 82]*	Twice daily	14 days
	Moxifloxacin 1% and dexamethasone 0.1% [86]*	Four times a day	7 days
	Tobramycin 0.3% and dexamethasone 0.05% [84]*	Twice daily × 2 days and then once daily	12 days
	Tobramycin 0.3% and loteprednol etabonate 0.05% [51, 55, 59]	1–2 drops every 4–6 h	2–4 weeks
Immunomodulators	Cyclosporine 0.5–1% [28, 61, 63, 65]	Twice daily	≥ 3 months
	Cyclosporine 2% [4]	Four times a day (and then tapered)	Rescue medication when azithromycin fails
	Tacrolimus 0.02–0.03% [66, 67,146a]	Twice daily	≥ 3 months
Other	Preservative-free lubricating eye drops	Four times a day or as needed	Long-term or as needed
	Nedocromil sodium/sodium cromoglycate [73, 74b]	Four times a day	N/A

N/A not applicable

^aOff-label use

^bAssists with corneal neovascularization

*Literature review shows these medications only used in adult populations

Tear Supplements

The lack of lipid in the tear film from congested MGs contributes to the development of evaporative-type dry eye, ocular surface disruption, and corneal epitheliopathy in PBKC [17, 22, 28, 36]. All classes of ocular lubricants, including viscosity-enhancing agents (i.e., hydroxypropyl, carboxymethyl cellulose, and polyvinyl-based tear supplements), hyaluronate-based agents, and lipomimetics can improve the superficial punctate keratopathy, dilute inflammatory mediators in the tear film, and provide symptomatic relief [23, 37]. These lubricants reduce tear hyperosmolarity, reduce friction between the conjunctiva and ocular surface, and improve the distribution of the lipid layer over the surface [23]. Preservative-free tear supplements may be used in the setting of corneal epitheliopathy where frequent applications may be required and benzalkonium chloride-related surface toxicity is of concern [38, 39]. Reduction of screen time may also be appropriate for children with a history of excessive screen time and who have dry eye findings [30].

Topical Antibiotics

Topical antibiotics, in the context of PBKC, are used to reduce surface microbial colonization, attenuate bacterial exotoxin load, and exert direct anti-inflammatory effects [17, 22, 37]. They can be used alone or in conjunction with other topical or systemic therapies [6, 18, 28, 40]. Macrolides are the most commonly used topical antibiotics for this condition, with the use of 0.5% erythromycin ointment and azithromycin drops most frequently reported in the literature [15, 17, 28, 30, 35, 35, 36, 41, 42]. Additionally, in vitro studies have shown that these antibiotics reduce the release of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNFα, and matrix metalloproteinase-9 (MMP-9), and mitigate neutrophil chemotaxis and phagocytosis [23, 43, 44]. Anti-inflammatory uses of topical macrolides are off-label but they have been reported to be well tolerated with minimal adverse effects. Topical erythromycin and azithromycin are typically used at a once-a-day or twice-a-day dosing, respectively, over a 1–6-month treatment period [22, 35, 45].

Other topical antibiotics reported in the literature include fluoroquinolones, chloramphenicol, fusidic acid, gentamicin, bacitracin, and ciprofloxacin [3, 6, 8, 17, 28, 36, 46–48]. A summary of antibacterial and antiparasitic treatment options for PBKC is outlined in Table 2.

Table 2.

Anti-infective treatment options for the management of pediatric blepharokeratoconjunctivitis associated with various microorganisms

Agent	Treatment
Demodex folliculorum and Demodex brevis	Tea-tree oil derivatives, lotilaner ophthalmic solution, ivermectin (oral or topical) [25, 105, 110, 111, 147]
Cutibacterium acnes*	Erythromycin (topical or oral), azithromycin (topical or oral), systemic tetracycline‡ [6, 18, 22, 46, 63]
Staphylococcus species (S. aureus and S. epidermidis)	Topical erythromycin, azithromycin, fluoroquinolones, chloramphenicol, fusidic acid, tobramycin, gentamycin, and bacitracin, oral macrolides and tetracyclines [3, 6, 7, 18, 22, 40, 46, 63, 89, 90]
Corynebacteriumspecies	Topical and systemic macrolides (erythromycin and azithromycin), topical fusidic acid [22, 46, 63, 89, 148]

*Formerly known as Propionibacterium acnes

^‡In adolescents

Anti-inflammatory Agents

Topical Corticosteroids

Topical glucocorticoids play a crucial role in PBKC treatment, providing acute control of surface inflammation and preventing corneal neovascularization (Fig. 4) [22, 29]. The use of topical glucocorticoids for treatment or prevention of corneal neovascularization is off-label. Pharmacologic agents such as dexamethasone, prednisolone, fluorometholone, and loteprednol are used in PBKC for their direct and rapid anti-inflammatory effects through phospholipase A₂ inhibition [49–52]. While effective, these agents are associated with several short- and long-term adverse effects, including an increase in intraocular pressure, cataract formation, and increased susceptibility to corneal infections in children [28, 30, 50]. Therefore, they are often used short-term only for PBKC, especially the more potent steroids such as prednisolone or dexamethasone [28, 30, 50]. In cases where a longer-term glucocorticoid is needed, lower potency formulations such as fluorometholone or loteprednol may be better options [28, 53–58]. Topical corticosteroids available in combination formulations with antibiotics such as bacitracin, neomycin, polymyxin B, or tobramycin can improve compliance with treatment, either in a liquid or an ointment formulation [30]. The typical treatment protocol involves four times daily dosing for 1–2 weeks, followed by a tapering and discontinuation of the treatment in 4–6 weeks [22, 30, 40]. Switching to a low-potency steroid as described above is desirable if long-term steroid treatment is required to maintain surface quiescence in vision-threatening disease [3].

Fig. 4.

Clinical photo of a pediatric eye with corneal neovascularization and corneal opacification before (a), during (b), and after (c) anti-inflammatory treatment

Topical Immunomodulators

Calcineurin inhibitors, such as cyclosporin A and tacrolimus, prevent T lymphocyte activation by blocking the IL-2 activation pathway and have been shown to reduce ocular surface and MG inflammation [28, 51, 52, 59]. These agents are typically used for long-term control of PBKC for patients who show recurrence of surface inflammation when topical steroids are discontinued [60, 61]. This group of medications does not suppress the local immune response or contribute to corneal stromal thinning, though ocular burning and stinging are common side effects [22, 60]. Various concentrations of cyclosporin A, ranging between 0.05% and 2%, have been shown to be effective at controlling inflammation and inducing the regression of corneal vascularization, through off-label use, though a protracted course of treatment for at least 3 months is required [17, 28, 60, 62, 63]. Tacrolimus 0.03%, another calcineurin inhibitor, has also been reported (off-label) to be effective in PBKC treatment [22, 64–66].

Lifitegrast is a topical eye formulation currently US Food and Drug Administration (FDA)-approved to treat dry eye disease in adults: one drop of lifitegrast 5% is used two times a day [67]. It is a lymphocyte function-associated antigen 1 antagonist that blocks the activation and migration of T cells to reduce inflammation [68]. As a result of the inflammatory nature of PBKC, there is growing interest in off-label use of lifitegrast, though there is limited information on the efficacy in pediatric patients.

Antihistamines and Mast Cell Stabilizers

The pathogenesis of PBKC in children with atopic conditions may involve eosinophils and mast cell degranulation [69–71]. Mast cells promote neutrophil recruitment and angiogenesis that can lead to corneal neovascularization in the setting of PBKC through the secretion of pro-angiogenic agents and stimulating vascular endothelial cell proliferation and tube formation [72–75]. There have been no studies specifically examining the role of mast cell inhibitors in PBKC, but off-label use of agents such as nedocromil sodium or sodium cromoglycate, at a standard dosing frequency of four times a day, may help attenuate corneal neovascularization in the setting of PBKC as a second-line treatment [72, 73].

Combination Therapies

With the development of antibiotic and steroid combination eye drops and ointments, these combination therapies have become increasingly popular for the treatment of PBKC [41, 76–82]. Common combination therapies include neomycin/polymyxin B/dexamethasone and tobramycin/dexamethasone combinations [30, 83, 84]. In adults, dexamethasone combined with azithromycin has been shown to be well tolerated and successful in reducing bacterial load and improving symptoms in blepharitis and blepharoconjunctivitis [41, 80, 81]. Additionally, combinations of dexamethasone with azithromycin, moxifloxacin, or tobramycin, and loteprednol and tobramycin have been shown to be effective in providing treatment in BKC [47, 81, 83, 85].

Systemic Treatment

Systemic treatment for PBKC is typically initiated when topical anti-inflammatory treatment is unable to control vision-threatening surface inflammation or when clinical evidence of severe active MGD is noted at the time of clinical evaluation and includes systemic antibiotics, systemic immunosuppressive or immunomodulatory treatment (Table 3).

Table 3.

Systemic medications for the management of pediatric blepharokeratoconjunctivitis

Type	Treatment	Dose & dosing schedule	Duration
Oral antibiotics	Erythromycin	125 mg every other day [6, 19]	6–8 months
		10–40 mg/kg/day or 500–660 mg/day twice or three times daily [2, 7, 11, 26, 50, 52, 87]
	Azithromycin	5–10 mg/kg/day [26, 29, 63, 88, 89]	4–6 weeks
			3 days a week × several weeks
	Doxycycline [7, 22a]	50–100 mg twice daily	6 weeks—several months
	Minocycline [7, 22a]	50–100 mg twice daily
	Oxytetracycline [7, 22a]	250 mg once a day–four times a day
	Amoxicillin with clavulanic acid [31]	400 mg/57 mg twice daily	1 month
Immunomodulatory agents	Azathioprine [8]	3 mg/kg/day	N/A
		50 mg/day, titrating to twice daily	N/A
	Mycophenolate mofetil [8]	250–750 mg, twice daily

N/A not applicable

^aTreatment of meibomian gland disease and pediatric ocular rosacea

Systemic Antibiotics

Oral antibiotics, such as macrolides and tetracyclines, have been effective in treating moderate to severe PBKC, as these therapies have both anti-inflammatory, lipid-modulatory, and antibacterial effects through penetration into MGs, especially in patients where topical therapies fail to induce remission [18].

Oral macrolides are more commonly used in PBKC in an off-label manner for their anti-inflammatory effects on the ocular surface, mediated through inhibition of pro-inflammatory cytokines and matrix metalloproteinases, and favorable side effect profile [22, 86]. Systemic erythromycin is used for PBKC and typically at a daily dose of 500–660 mg or 10–40 mg/kg body weight, administered in two or three doses over 7 to 12 months [2, 7, 11, 17, 49, 51, 87]. A low dose of 125 mg every other day has been shown to significantly reduce disease recurrence for patients with PBKC [6, 15]. More recently, azithromycin dosed at 5–10 mg/kg daily for at least 4 weeks has been shown to be an effective treatment for chronic severe bilateral PBKC, though several centers have different treatment protocols [30, 62, 88, 89]. Repetitive cycles consisting of 3–5-day course intervals are also reported, though some of these reports involve adult subjects [17, 29, 62, 88, 88, 89]. Azithromycin has the advantage of better bioavailability, a longer half-life, and a higher tissue drug concentration and is currently preferred to erythromycin for the treatment of PBKC [90]. The most common adverse effect is gastrointestinal upset and other rare side effects include allergic reactions, sensorineural hearing loss, and increased risk of cardiac arrhythmias [91–94].

The dosing of doxycycline and minocycline is 50 mg to 100 mg once or twice daily, while oxytetracycline can be dosed at 250 mg one to four times daily for MGD and ocular rosacea [7, 23]. Of note, while tetracyclines also have similar anti-inflammatory effects on the ocular surface as macrolides, due to their association with permanent tooth discoloration, the routine use of tetracyclines is not recommended in children aged less than 9–12 years until dentition is complete [6, 95]. However, the degree of discoloration varies depending on the total dose and exact timing of tooth development [96–98]. Doxycycline has been reported to potentially have the lowest incidence of staining within the tetracycline family due to its relatively decreased affinity for calcium binding and lower concern on bone development [97, 99]. There is also concern about tetracycline’s effects on bone development, though the direct impact is not well established [100]. Other side effects of doxycycline include gastrointestinal upset, photosensitivity, esophageal irritation, and allergic skin reactions [101].

Systemic amoxicillin with clavulanic acid has been used to treat PBKC with comparable efficacy compared to macrolide treatment, though evidence is currently limited to a few reports [31].

Demodex Treatment

Treating demodex infestation in PBKC helps remove antigenic stimuli from the ocular surface [102–104]. There are a wide range of medical treatment options, most of which involve the use of tea tree oil and its derivatives [105–108]. Other treatment options include topical sulfur products, permethrin, and ivermectin. Lotilaner 0.25% ophthalmic solution (Tarsus Pharmaceuticals, Irvine, CA, USA) is the first FDA-approved treatment in adults with Demodex blepharitis, although no pediatric studies have been performed [109–111].

Systemic Immunomodulation

In cases of severe or refractory vision-threatening PBKC, off-label use of short-term oral corticosteroids as well as longer-term immunomodulatory agents such as cyclosporine, azathioprine, and mycophenolate mofetil may be considered to induce remission [8, 27, 29]. Orally administered cyclosporine has been shown to be modestly effective at controlling ocular inflammation in adults, but no studies exist in children [51].

Other

Dietary supplementation with omega-3 essential fatty acids (EFAs) has been shown to inhibit inflammation and improve MG function in MGD and BKC [6, 37]. These fatty acids are found in oily fish such as salmon and flaxseed oil. Regular intake of these EFAs through diet or supplements has been associated with decreased tear evaporation, decreased ocular surface inflammation, and increased symptom relief in MGD and PBKC, though there is still controversy on the efficacy of essential EFA supplementation [6, 37, 112, 113]. In a retrospective case series of patients with PBKC, a daily dose of 2.5 mg flaxseed oil was found to prevent disease exacerbations, particularly in patients who experienced disease recurrence when systemic antibiotics were discontinued [6].

There are several FDA-approved in-office treatments for MGD in adults, including thermal pulsation devices and intense pulsed light (IPL) therapy. Thermal pulsation devices heat and express clogged meibomian glands and many studies have shown that these devices improve the signs and symptoms of MGD [114–118]. IPL therapy reduces capillary dilation on the eyelid margins and has been shown to have anti-inflammatory effects on the eyelid and significantly shorten the duration of BKC [119–121]. Patients with ocular rosacea have also been shown to benefit from long-term IPL therapy [122]. There is limited information on the use of these devices in children, with one study showing that IPL therapy may be superior to traditional hot compress therapy for chalazion treatment and another suggesting that IPL therapy could be a safe and effective treatment for moderate-to-severe pediatric blepharitis [123, 124]. Since chalazia and blepharitis are possible clinical manifestations of PBKC, these therapies could play a more prominent role in PBKC treatment in the future.

There have been a few case studies reporting the use of corticosteroid injections, either sub-tenon or subconjunctival, to treat severe or refractory cases of PBKC [33, 125]. The injections were associated with improved clinical signs, including reduced corneal infiltrates and corneal neovascularization, and facilitated symptom resolution in a subset of patients. Of note, one case report described the use of subconjunctival triamcinolone in combination with subconjunctival bevacizumab [33].

Novel and Emerging Therapies

While the inflammatory and active component of PBKC can often be controlled and resolved with the above regimens, patients may still be left with center-involving corneal scarring. Topical losartan, an angiotensin II receptor blocker, is under investigation for its potential utility in the treatment of corneal scarring, though not specifically in PBKC [126]. In rabbit studies, losartan was found to inhibit the activity of myofibroblasts, which contribute to corneal scarring after injury [127]. This drug may be of benefit for chronic treatment of stromal scarring in the central visual axis once the active inflammatory course of PBKC is treated.

Lastly, there is growing interest in examining the relationship between the gut microbiome and ophthalmologic diseases, as well as investigating the bacterial microbiota of the conjunctiva and eyelid margins [128–131]. Studies have suggested the existence of a gut–eye microbiota axis, though no recent studies have linked gut microbiota dysbiosis to PBKC [132, 133].

Multidisciplinary Approach

Treatment of PBKC often requires a multidisciplinary approach, involving not just pediatric ophthalmologists and cornea specialists but also dermatologists, allergists, and contact lens specialists. Pediatric ocular rosacea and atopic dermatitis may coexist and would benefit from specialized care [7, 9, 10, 134–136]. Management of systemic allergies requires consultation with an allergy/immunology specialist, which would help control allergic symptoms and surface inflammation. In some instances, a gastrointestinal consultation may be warranted, as it has been suggested that parasitic/helminthic infections may cause phlyctenular keratoconjunctivitis [20, 137–140].

Visual rehabilitation, after the disease is brought under remission, is crucial for pediatric patients who are in their critical period of visual development [141]. Amblyopia can develop as a result of central corneal opacification or induced astigmatism and higher-order aberrations [6]. Biannual refractions for these cases are recommended to address refractive changes that can occur from changing corneal topographic features. Amblyopia treatment is typically performed with part-time occlusion, and intervals up to half of awake hours may be utilized for deprivational amblyopia. Correction of refractive errors can be undertaken with eyeglasses or contact lenses [142–144]. Soft, rigid gas-permeable, or scleral contact lenses can be employed depending on the refractive needs of the eye, such as irregular astigmatism. While all three types of contact lenses offer benefits such as addressing refractive errors, scleral contact lenses also help protect the corneal surface with a continuous aqueous reservoir [76–79].

Special Considerations in Pediatric Populations

There are several unique considerations when treating PBKC. In general, children are reliant on adult caregivers for their treatment, and as such, it is crucial that the caregivers are made aware of the importance of adherence to treatment. Barriers to instillation of eye medications, such as patient discomfort and apprehension, should be addressed [145]. Additionally, there may be developmental and cognitive factors that can interfere with a successful treatment plan. An important part of PBKC treatment involves daily eyelid hygiene measures, which can be challenging to build into both the child’s and caregiver’s schedule. Amblyopia treatment also adds a daily time burden for families, which can hinder adherence and delay remission, potentially worsening visual outcomes even when inflammation is controlled. Regular follow-up appointments are recommended to reinforce the treatment plan and early identification of treatment failure.

Conclusions

Management of PBKC is multidimensional, involving eyelid hygiene, topical antibacterial and anti-inflammatory therapies, systemic treatment for severe cases, dietary modifications, and amblyopia management, often requiring multidisciplinary care. Ophthalmologists should be aware of the new diagnostic criteria of PBKC, along with its interconnected treatment options, to guide appropriate intervention. Preventing vision loss from corneal scarring should be a primary goal, and all available therapies should be strategically employed to achieve rapid remission and preserve visual function.

Author Contributions

Catherine Wang – Drafting the manuscript, literature review. Anne Zeng – Drafting the manuscript, literature review. Hajirah N Saeed – Concept and design, reviewing and editing manuscript. Ali R Djalilian – Concept and design, reviewing and editing manuscript. Mehmet C Mocan – Concept and design, drafting the manuscript, reviewing and editing manuscript, literature review.

Funding

This work was supported by an unrestricted departmental grant from the Research to Prevent Blindness. No funding or sponsorship was received for the publication of this article.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Catherine Wang, Anne Zeng, Hajirah N Saeed, Ali R Djalilian, and Mehmet C Mocan have no relevant disclosures.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.