{"paper_id":"1bfc2e54-d852-490b-8f69-5b63005603b7","body_text":"Long-term treatment outcomes of pediatric blepharokeratoconjunctivitis without systemic antibiotics | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Long-term treatment outcomes of pediatric blepharokeratoconjunctivitis without systemic antibiotics Haryung Park, Young Joon Choi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7154264/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The optimal treatment of pediatric blepharokeratoconjunctivitis (PBKC) is not well established, and systemic antibiotic therapy is considered an important component of its management. This study aimed to report the therapeutic outcomes of PBKC in the absence of long-term systemic antibiotic therapy. Methods This retrospective case series included patients with PBKC aged < 18 years who visited Ajou University Medical Center between May 2020 and July 2022. The patients were treated with lid scrubs and topical ocular therapies. We excluded those with less than 3 months of follow-up or systemic antibiotic use. Based on the severity of PBKC, treatments included lid scrubs, topical antibiotics, steroids, and immunomodulatory drugs. Clinical characteristics and disease flare-ups were monitored. Results Of the 34 patients identified, 21 patients were included. Overall, 2 of the excluded patients used systemic antibiotics, and 11 patients had less than 3 months of follow-up. The mean age was 10.7 years, and the mean follow-up duration was 10.24 months. The Oxford staining score, blepharitis grading scale score, and lid margin telangiectasia grade improved with treatment. In total, 2/21 patients (14%) experienced flare-ups during the follow-up period; these were controlled with topical antibiotics and steroids within 1 month. Conclusion PBKC can be controlled with lid scrubs and topical ocular therapies without long-term systemic antibiotic therapy. Additional therapeutic studies and clinical trials are required to establish more effective treatment strategies. Blepharokeratoconjunctivitis Meibomitis blepharitis phlyctenulosis pediatric Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Pediatric blepharokeratoconjunctivitis (PBKC), also called pediatric meibomitis-related keratoconjunctivitis, is a poorly defined inflammatory disease that involves the eyelids, conjunctiva, and corneas. Importantly, PBKC is often recurrent and vision-threatening.(1–3) However, PBKC is commonly underdiagnosed or diagnosed late because of its nonspecific signs and symptoms, making it challenging to differentiate it from other ocular surface disorders.(4) In 2023, efforts to standardise the definition and diagnostic criteria of PBKC were published by Morales et al. PBKC was defined as ‘a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement, ranging from superficial punctate keratitis to corneal infiltrates with vascularisation and scarring.’(5) Although not yet standardised, the usual treatment for PBKC involves a combination of eyelid hygiene; topical steroid-antibiotic combinations; and systemic antibiotics, which focus on clearing meibomian gland secretions, rectifying ocular surface dysbiosis, and alleviating ocular surface inflammation.(6–8) Eyelid hygiene is fundamental and includes practices such as warm compresses and eyelid scrubs. Topical antibiotics and anti-inflammatory drugs are commonly used to manage mild to moderate cases, whereas more intensive treatment may be required for severe cases or those with corneal involvement. Systemic antibiotics such as erythromycin, doxycycline, and cephalosporins are prescribed for their anti-bacterial and anti-inflammatory properties.(6) Despite the recognised efficacy of systemic antibiotics in the management of PBKC, their use in pediatric patients poses significant challenges. The long-term use of systemic antibiotics in children can lead to various adverse effects, including gastrointestinal disturbances, antibiotic resistance, and potential impacts on growth and development. In addition, the options for systemic antibiotics suitable for prolonged use in children are limited.(8, 9) These limitations necessitate the exploration of alternative treatment strategies to effectively manage PBKC without relying heavily on systemic antibiotics. This retrospective case series aimed to evaluate the treatment outcomes of PBKC managed without systemic antibiotics. By examining the clinical responses and outcomes of children treated with alternatives, this study aimed to provide insights into the feasibility and effectiveness of topical treatment protocols for PBKC. MATERIALS AND METHODS Study design and patients This retrospective observational case study was approved by the Institutional Review Board of Ajou University Hospital (AJOUIRB-DB-2022-311) and followed the principles of the Declaration of Helsinki. The requirement for informed consent was waived by the IRB as the study involved a retrospective review of medical records, for which obtaining consent from each participant was impractical. Furthermore, the study was classified as minimal risk, with no anticipated adverse effects on the safety, rights, or welfare of the participants. The medical records of patients aged younger than 18 years with a clinical diagnosis of PBKC and who visited the Ajou University Hospital Ophthalmology Outpatient Clinic between March 2020 and July 2022 were reviewed. The inclusion criteria for diagnosis were the presence of blepharitis or meibomitis accompanied by corneal inflammatory infiltration, superficial corneal neovascularisation, or superficial punctate keratopathy (Supplemental Fig. 1). All included patients were treated without systemic antibiotics. Patients with a follow-up period of less than 3 months and those who underwent systemic antibiotic treatment for any reason were excluded. Demographic characteristics including age at the time of diagnosis were recorded. Assessment and follow-up At every follow-up visit, the eyelids, conjunctiva, and corneas of the patients were examined under a slit-lamp biomicroscope with fluorescein staining. The presence of dermatological rosacea, corneal involvement, corneal neovascularisation, phlyctenulosis, and bilateral eye involvement was recorded. Corneal and conjunctival erosions were assessed using the Oxford staining score (0–5) following fluorescein staining with a fluorescein dye paper.(10) Blepharitis was graded on a scale from 0 (normal) to 4 (severe) using the Efron grading scale for contact lens complications.(11) Lid margin vascularity was graded on the scale from 0 (no findings) to 3 (severe telangiectasia or redness).(12) As an acute therapy, patients with PBKC were treated with topical antibiotics (0.5% levofloxacin hydrate, 0.3% tobramycin, or 0.5% moxifloxacin hydrochloride) and topical steroids (0.1% fluorometholone or 0.5% loteprednol etabonate, depending on the severity of PBKC) four times a day for less than 2 months. Systemic steroids were administered in some patients with severe corneal pathology. After active inflammation resolved, all patients were instructed to maintain lid hygiene using a tea tree oil-containing lid scrub (OCuSOFT Oust Demodex TTOMAX, Rosenberg, TX). Additionally, the patients were started on topical immune-modulating drugs, such as 0.05% cyclosporine, 0.1% cyclosporine, or 0.03% tacrolimus ointment mixed 1:1 with artificial tear ophthalmic ointment, for chronic disease control. These treatments were gradually tapered. The lid hygiene was maintained until the end of the treatment period (Table 1 ). Table 1 Treatment strategy for pediatric blepharokeratoconjunctivitis Regimen type Component 1. Regimens for active inflammation control Topical antibiotics and steroids Oral steroids in vision-threatening cases 2. Regimens for chronic disease control Tea tree oil-containing lid scrub, twice daily Topical cyclosporin 0.05% or topical cyclosporin 0.1% or topical tacrolimus (ointment) 0.03%: artificial tear ointment 1:1 mix Statistics The changes in Oxford staining score, blepharitis grading scale score, and lid margin vascularity grade were analysed using a mixed-effects model to account for missing data. All statistical analyses were performed using SPSS version 21.0 (SPSS Inc., Chicago, IL, USA) and Prism 8, GraphPad software (San Diego, USA). A P-value of < 0.05 was considered significant. RESULTS Patient characteristics Overall, 21 patients were included. The demographic and clinical features of PBKC patient are summarised in Table 2 , and detailed data for each patient are provided in Supplemental Table 1. The mean age at the first visit was 10.71 years (range: 2–17 years), and the mean follow-up period was 10.2 months (range: 2–20 months). Overall, 15 patients (71%) were female. A total of 9 patients (43%) had bilateral PBKC, and 12 (57%) patients had a history of chalazia. None of the patients had a history of dermatological rosacea. Fifteen patients (71%) had new corneal vessels, and 6 patients (29%) had corneal phlyctens. Table 2 Summary of characteristics of the patients with pediatric blepharokeratoconjunctivitis N Mean age (years) Mean F/U duration (months) Female Bilateral History of chalazia Dermatologic rosacea Meibomian gland abnormality Corneal infiltrates Corneal NV Phlycten type 21 10.71 (2–17) 10.24 (3–20) 71% (15/21) 43% (9/21) 57% (12/21) 0% 100% 100% 71% (15/21) 29% (6/21) Abbreviations: F/U, follow up; NV, neovascularization Change in erosions, blepharitis, and lid margin vascularity The changes in Oxford staining score, blepharitis grading scale score, and lid margin vascularity grade of the PBKC patients are shown in Figs. 1 . At all-time points, all three scores were significantly lower than baseline. (P < 0.001 for all). This indicated that PBKC was effectively controlled with lid scrubs and topical ocular therapies, without the need for systemic antibiotics. Furthermore, keratitis and blepharitis associated with PBKC improved over time with long-term maintenance therapy. The representative photographs of eyelid changes in patients with PBKC during treatment are shown in Fig. 2 (A-C) and Supplemental Fig. 2. Blepharitis and meibomitis of PBKC have chronic features that change slowly over time, and it is difficult to evaluate their improvement and deterioration. However, a comparison of the serial photographs revealed that most patients showed improvement in blepharitis and meibomitis. Change in corneal phlyctenulosis Representative photographs of the changes in corneal phlyctenulosis in patients with PBKC during treatment are presented in Fig. 2 (D-F) and Supplemental Fig. 3. Most cases of corneal phlyctenulosis stabilised with topical antibiotics and steroids within 1 month and resolved with minimal residual signs when managed with the chronic disease control regimens described in Table 1 . Recurrence occurred in two patients who did not adhere well to treatment; however, those who followed the medication regimen experienced no significant recurrence or complications. Change in steroid use in combination with chronic disease control regimens The changes in the medications used during the follow-up of patients with PBKC are shown in Fig. 3 . In this analysis, ‘steroid use’ was defined as regular steroid use under physician guidance. During the follow-up period, the percentage of eyes receiving topical steroid treatment decreased from 71% at 1 month to 14% at 3 months and to 0% at 6 months. After 9 months, only 2 patients restarted steroid treatment, and these patients had poor adherence to chronic disease control regimens. One 14-year-old boy (Case No. 5 in Supplemental Table 1), who had previously been treated for phlyctenulosis, developed recurrence at month 9 of treatment owing to poor treatment compliance. The patient required short-term oral steroids to control the recurrent disease. The other patient was a 12-year-old boy (Case No. 10 in Supplemental Table 1) who did not visit the clinic on the scheduled date and did not take his medications regularly. He required topical steroids and had to use them often until the last visit. DISCUSSION This study examined the clinical outcomes of patients with PBKC who were not treated with systemic antibiotics. The patients with PBKC were managed using topical antibiotics and steroids during the acute phase, followed by a tea tree oil-containing lid cleaner and a topical immunomodulating agent for chronic disease control. Using this approach, we were able to effectively control PBKC with minimal recurrence, and the blepharitis improved over time. Clinically significant reactivation was observed only in patients with poor treatment compliance. PBKC is one of the most neglected eye diseases despite its potential to cause permanent vision-threatening sequelae.(13) There had been no precise definition of this condition, leading to the use of various terms such as meibomitis-related keratoconjunctivitis, pediatric ocular rosacea, phlyctenular keratitis, and childhood blepharokeratoconjunctivitis.(14) Fortunately, through the efforts of experts, the condition has been formally named PBKC and classified as PBKC and PBKC suspect.(5) As PBKC is often accompanied by inflammatory meibomitis, many clinicians may misdiagnose it as pediatric meibomian gland dysfunction (MGD). However, MGD is primarily a causative condition of evaporative dry eye resulting from chronic obstruction of the meibomian glands.(15) In contrast, PBKC exhibits characteristics that are more aligned with inflammatory keratitis than dry eye disease. Therefore, clinicians should consider these two conditions distinct disease entities. Meibomitis is one of the main triggering factors in the pathogenesis of PBKC, and its possible causes include Propionibacterium acnes , Staphylococci, and Demodex mites.(14) Suzuki et al. performed both aerobic and anaerobic bacterial cultures of meibum from patients with PBKC and found that P. acnes may be involved in meibomitis.(16, 17) Propionibacterium acnes has long been known to cause inflammation. It can induce a delayed-type hypersensitivity response similar to that of Mycobacterium tuberculosis , which is thought to be responsible for phlyctenular keratitis.(18–20) Staphylococcus, one of the most common microorganisms found on the eyelids and conjunctiva, can cause blepharitis and meibomitis, leading to marginal keratitis.(21, 22) In addition, Demodex mites are closely associated with blepharitis.(23),(24) These microorganisms are believed to play significant roles in the pathogenesis of PBKC. Consequently, antibiotics are considered an important component in the treatment of PBKC, and long-term systemic oral antibiotic use is commonly employed to manage the disease and prevent recurrence.(14) However, the range of antibiotics suitable for pediatric patients is limited, and prolonged oral administration is challenging. Given the uncertainty regarding whether these microorganisms represent infections or infestations, we hypothesised that topical treatment alone could provide some level of control. Therefore, this study examined whether PBKC could be effectively controlled without the need for systemic antibiotic therapy. Blepharitis and meibomitis have chronic courses that evolve slowly over time, and there is no objective indicator to assess disease severity, particularly in pediatric patients. It was difficult to assess the progression of blepharitis at each visit; however, by collecting and comparing photographs over time, we were able to confirm that improvement was achieved with chronic disease control regimens without the use of systemic antibiotics (Figs. 1 – 2 A–C). Corneal phlyctenulosis, which typically results from delayed hypersensitivity, is a severe form of keratitis. Corneal phlyctenulosis in patients with PBKC initially appeared to be resistant to treatment and may leave permanent sequelae. However, as shown in Fig. 2 D–F, corneal phlyctenulosis can completely resolve with appropriate treatment, with minimal recurrence. We recommended the use of tea-tree oil-containing lid scrub agents owing to their antibacterial and anti-demodex properties. Tea tree oil is a volatile essential oil derived from the Australian native plant Melaleuca alternifolia and is incorporated as an active ingredient in many topical formulations used to treat cutaneous infections.(25) Tea tree oil is well known for its effectiveness against the demodex mite.(26, 27) In addition, tea tree oil has sufficient antibacterial effects to target P. acnes and Staphylococci, which are implicated in the development of PBKC.(28, 29) Blepharitis and meibomitis associated with PBKC differ from meibomian gland dysfunction owing to the involvement of microorganisms, making tea tree oil-containing lid scrubs an important component in the treatment of PBKC. Cyclosporine and tacrolimus are calcineurin inhibitors that are used to treat various inflammatory conditions of the ocular surface. Notably, tacrolimus has 10–100 times greater immunosuppressive potency than cyclosporine,(30) and its therapeutic effects on PBKC have been reported before.(31, 32) Although the exact pathogenesis of PBKC has not yet been fully elucidated, calcineurin inhibitors typically suppress T cell function, suggesting that delayed-type hypersensitivity may play a key role.(30) This study has several limitations. It was conducted retrospectively, meaning that there was no control group, making it difficult to determine the necessity of systemic antibiotics in patients with PBKC. PBKC is relatively rare and primarily affects children, posing challenges in conducting clinical trials. However, the recent establishment of a formal definition of PBKC marks an important first step toward clarifying this disease. If we can establish objective descriptions and scaled measurements for disease characteristics such as the severity of meibomitis, blepharitis, and phlyctenulosis, more definitive conclusions could be drawn, even in retrospective studies. In conclusion, PBKC can be effectively controlled with lid scrubs and topical ocular therapies without the need for long-term systemic antibiotics. Further studies, well-designed clinical trials in particular, are needed to establish precise and effective treatment strategies. Declarations Precis This study demonstrates effective control of pediatric blepharokeratoconjunctivitis (PBKC) using lid scrubs and topical therapies without systemic antibiotics while also highlighting that long-term maintenance therapy improves keratitis and blepharitis associated with PBKC. Ethics approval and consent to participate This retrospective observational case study was approved by the Institutional Review Board of Ajou University Hospital (AJOUIRB-DB-2022-311) and was conducted in accordance with the principles of the Declaration of Helsinki. The requirement for informed consent was waived by the IRB as the study involved a retrospective review of medical records, for which obtaining consent from each participant was impractical. Furthermore, the study was classified as minimal risk, with no anticipated adverse effects on the safety, rights, or welfare of the participants. Consent for publication All authors have reviewed the manuscript and provided their consent for publication. No identifiable personal data are included in this manuscript. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare no proprietary or financial interests in any materials or methods mentioned in this study. Funding This work was supported by the Basic Science Research Program (NRF-2022R1C1C1007243) of the National Research Foundation. Authors' contributions Y.J.C. designed the project, and H.P. and Y.J.C. analysed the results. H.P. and Y.J.C. wrote the manuscript. H.P. and Y.J.C. revised the manuscript critically. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of this work. Acknowledgements The authors thank Editage for English language editing. References Hamada S, Khan I, Denniston AK, Rauz S. Childhood blepharokeratoconjunctivitis: characterising a severe phenotype in white adolescents. The British journal of ophthalmology. 2012;96(7):949-55. Rodriguez-Garcia A, Gonzalez-Godinez S, Lopez-Rubio S. Blepharokeratoconjunctivitis in childhood: corneal involvement and visual outcome. Eye. 2016;30(3):438-46. Moon J, Lee J, Kim MK, Hyon JY, Jeon HS, Oh JY. Clinical Characteristics and Therapeutic Outcomes of Pediatric Blepharokeratoconjunctivitis. Cornea. 2023;42(5):578-83. Gupta N, Dhawan A, Beri S, D'Souza P. Clinical spectrum of pediatric blepharokeratoconjunctivitis. J AAPOS. 2010;14(6):527-9. Morales-Mancillas NR, Velazquez-Valenzuela F, Kinoshita S, Suzuki T, Dahlmann-Noor AH, Dart JKG, et al. Definition and Diagnostic Criteria for Pediatric Blepharokeratoconjunctivitis. JAMA ophthalmology. 2024;142(1):39-47. Suzuki T. Inflamed Obstructive Meibomian Gland Dysfunction Causes Ocular Surface Inflammation. Investigative ophthalmology & visual science. 2018;59(14):DES94-DES101. Ortiz-Morales G, Morales-Mancillas NR, Paez-Garza JH, Rodriguez-Garcia A. Letter Regarding: Clinical Characteristics and Therapeutic Outcomes of Pediatric Blepharokeratoconjunctivitis. Cornea. 2023;42(6):e10-e1. Rousta ST. Pediatric blepharokeratoconjunctivitis: is there a 'right' treatment? Current opinion in ophthalmology. 2017;28(5):449-53. Cetinkaya A, Akova YA. Pediatric ocular acne rosacea: long-term treatment with systemic antibiotics. American journal of ophthalmology. 2006;142(5):816-21. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003;22(7):640-50. Efron Grading Scales for Contact Lens Complications ( Millennium edition ) [Internet]. Butterworth-Heinemann. 2000. Available from: https://eprints.qut.edu.au/11857/1/11857a.pdf. Arita R, Minoura I, Morishige N, Shirakawa R, Fukuoka S, Asai K, et al. Development of Definitive and Reliable Grading Scales for Meibomian Gland Dysfunction. American journal of ophthalmology. 2016;169:125-37. Teo L, Mehta JS, Htoon HM, Tan DT. Severity of pediatric blepharokeratoconjunctivitis in Asian eyes. American journal of ophthalmology. 2012;153(3):564-70 e1. Suzuki T, Teramukai S, Kinoshita S. Meibomian glands and ocular surface inflammation. The ocular surface. 2015;13(2):133-49. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, et al. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Investigative ophthalmology & visual science. 2011;52(4):1930-7. Suzuki T, Mitsuishi Y, Sano Y, Yokoi N, Kinoshita S. Phlyctenular keratitis associated with meibomitis in young patients. American journal of ophthalmology. 2005;140(1):77-82. Suzuki T. Meibomitis-related keratoconjunctivitis: implications and clinical significance of meibomian gland inflammation. Cornea. 2012;31 Suppl 1:S41-4. Webster GF, Leyden JJ. Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes. Inflammation. 1980;4(3):261-9. Webster GF, Leyden JJ, Norman ME, Nilsson UR. Complement activation in acne vulgaris: in vitro studies with Propionibacterium acnes and Propionibacterium granulosum. 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In vitro and in vivo killing of ocular Demodex by tea tree oil. The British journal of ophthalmology. 2005;89(11):1468-73. Gao YY, Di Pascuale MA, Elizondo A, Tseng SC. Clinical treatment of ocular demodecosis by lid scrub with tea tree oil. Cornea. 2007;26(2):136-43. Raman A, Weir U, Bloomfield SF. Antimicrobial effects of tea-tree oil and its major components on Staphylococcus aureus, Staph. epidermidis and Propionibacterium acnes. Lett Appl Microbiol. 1995;21(4):242-5. Christoph F, Kaulfers PM, Stahl-Biskup E. A comparative study of the in vitro antimicrobial activity of tea tree oils s.l. with special reference to the activity of beta-triketones. Planta Med. 2000;66(6):556-60. Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo). 1987;40(9):1256-65. Kymionis GD, Kankariya VP, Kontadakis GA. Tacrolimus ointment 0.03% for treatment of refractory childhood phlyctenular keratoconjunctivitis. Cornea. 2012;31(8):950-2. Yoon CH, Kim MK, Oh JY. Topical Tacrolimus 0.03% for Maintenance Therapy in Steroid-Dependent, Recurrent Phlyctenular Keratoconjunctivitis. Cornea. 2018;37(2):168-71. Additional Declarations No competing interests reported. Supplementary Files BMCOphMRKCNoantiSupple02.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7154264\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":504661252,\"identity\":\"25c15236-0d61-4efd-9482-15872b0fc807\",\"order_by\":0,\"name\":\"Haryung Park\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ajou University School of Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Haryung\",\"middleName\":\"\",\"lastName\":\"Park\",\"suffix\":\"\"},{\"id\":504661253,\"identity\":\"8263081d-2cd9-400d-a637-d0194b8e2a4f\",\"order_by\":1,\"name\":\"Young Joon Choi\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYDACZmTOByBmYydGywEom3EGSAszbsUIANPCzINhLxYg3857+PWHim1y5rMPH5O2+bVNno+ZgfHDxxzcWgwO86VZHDhz21jmXFqadG7fbcM2ZgZmyZnb8Ghh5jEzONh2O3EGD4/Z7dye24xALWzMvHi0yDcja7HsuW1PUAvDYR7jB3AtDD9uJxLUYnCYx4zhDNAvEjxs6T97G24ntzEzNuP1i3z/GeMPFRW35SR4mA8b/Phz23Z+e/PBDx/xOQwYdxJwJmMbmGzAqx4ImD8g2H8IKR4Fo2AUjIKRCADzIE3vkGXGbAAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Ajou University School of Medicine\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Young\",\"middleName\":\"Joon\",\"lastName\":\"Choi\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-07-18 05:53:21\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-7154264/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-7154264/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":89986433,\"identity\":\"50f48147-f2db-49c6-8f26-5fdf6381833d\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:54:28\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":126613,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe mean Oxford staining scores (A), blepharitis grading scale (B), and lid margin vascularity grade (C) at baseline and post-treatment. The mean values and standard deviations are depicted. Scores at each time point were statistically significantly lower compared to baseline scores. (mixed-effects model, P \\u0026lt; 0.001)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"MRKCFigure01.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7154264/v1/cccd53861d316fd970da4408.png\"},{\"id\":89986423,\"identity\":\"75164495-6817-4e6a-ac6a-91a41e823255\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:54:27\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":1928201,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003ePre- and posttreatment changes in eyelids and corneal phlyctenulosis in the patients with pediatric blepharokeratoconjunctivitis (PBKC)\\u003c/p\\u003e\\n\\u003cp\\u003eA-C: The eyelid of a 12-year-old female (Case 21) before (A), 1 month posttreatment (B), and 3 months posttreatment (C). D-F: The cornea of a 13-year-old female (Case 3) before treatment (D), 3 weeks posttreatment (E), and 3 months posttreatment (F)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"MRKCFigure02.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7154264/v1/745c846d9722a42a771320f2.png\"},{\"id\":89986402,\"identity\":\"b569bd01-8345-48bf-b3a2-751a975146c4\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:54:22\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":32511,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChanges in treatment over time. The proportion of topical steroid use decreases during the treatment period\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"MRKCFigure03.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7154264/v1/518458ed17d4dca66fab8dd6.png\"},{\"id\":93464077,\"identity\":\"8b011d51-c924-4a07-bd15-aa5816deb6f2\",\"added_by\":\"auto\",\"created_at\":\"2025-10-14 06:54:08\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":5049004,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7154264/v1/dca71e70-5e62-4b9c-ad9f-9c1f7b747200.pdf\"},{\"id\":89986424,\"identity\":\"4258cc87-eda6-4663-8233-42b9135e5a2e\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:54:27\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":2910362,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"BMCOphMRKCNoantiSupple02.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7154264/v1/2689890c8aad26272dda188c.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Long-term treatment outcomes of pediatric blepharokeratoconjunctivitis without systemic antibiotics\",\"fulltext\":[{\"header\":\"INTRODUCTION\",\"content\":\"\\u003cp\\u003ePediatric blepharokeratoconjunctivitis (PBKC), also called pediatric meibomitis-related keratoconjunctivitis, is a poorly defined inflammatory disease that involves the eyelids, conjunctiva, and corneas. Importantly, PBKC is often recurrent and vision-threatening.(1\\u0026ndash;3) However, PBKC is commonly underdiagnosed or diagnosed late because of its nonspecific signs and symptoms, making it challenging to differentiate it from other ocular surface disorders.(4) In 2023, efforts to standardise the definition and diagnostic criteria of PBKC were published by Morales et al. PBKC was defined as \\u0026lsquo;a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement, ranging from superficial punctate keratitis to corneal infiltrates with vascularisation and scarring.\\u0026rsquo;(5)\\u003c/p\\u003e\\u003cp\\u003eAlthough not yet standardised, the usual treatment for PBKC involves a combination of eyelid hygiene; topical steroid-antibiotic combinations; and systemic antibiotics, which focus on clearing meibomian gland secretions, rectifying ocular surface dysbiosis, and alleviating ocular surface inflammation.(6\\u0026ndash;8) Eyelid hygiene is fundamental and includes practices such as warm compresses and eyelid scrubs. Topical antibiotics and anti-inflammatory drugs are commonly used to manage mild to moderate cases, whereas more intensive treatment may be required for severe cases or those with corneal involvement. Systemic antibiotics such as erythromycin, doxycycline, and cephalosporins are prescribed for their anti-bacterial and anti-inflammatory properties.(6)\\u003c/p\\u003e\\u003cp\\u003eDespite the recognised efficacy of systemic antibiotics in the management of PBKC, their use in pediatric patients poses significant challenges. The long-term use of systemic antibiotics in children can lead to various adverse effects, including gastrointestinal disturbances, antibiotic resistance, and potential impacts on growth and development. In addition, the options for systemic antibiotics suitable for prolonged use in children are limited.(8, 9) These limitations necessitate the exploration of alternative treatment strategies to effectively manage PBKC without relying heavily on systemic antibiotics.\\u003c/p\\u003e\\u003cp\\u003eThis retrospective case series aimed to evaluate the treatment outcomes of PBKC managed without systemic antibiotics. By examining the clinical responses and outcomes of children treated with alternatives, this study aimed to provide insights into the feasibility and effectiveness of topical treatment protocols for PBKC.\\u003c/p\\u003e\"},{\"header\":\"MATERIALS AND METHODS\",\"content\":\"\\u003cp\\u003e\\u003cb\\u003eStudy design and patients\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e This retrospective observational case study was approved by the Institutional Review Board of Ajou University Hospital (AJOUIRB-DB-2022-311) and followed the principles of the Declaration of Helsinki. The requirement for informed consent was waived by the IRB as the study involved a retrospective review of medical records, for which obtaining consent from each participant was impractical. Furthermore, the study was classified as minimal risk, with no anticipated adverse effects on the safety, rights, or welfare of the participants.\\u003c/p\\u003e\\u003cp\\u003eThe medical records of patients aged younger than 18 years with a clinical diagnosis of PBKC and who visited the Ajou University Hospital Ophthalmology Outpatient Clinic between March 2020 and July 2022 were reviewed. The inclusion criteria for diagnosis were the presence of blepharitis or meibomitis accompanied by corneal inflammatory infiltration, superficial corneal neovascularisation, or superficial punctate keratopathy (Supplemental Fig.\\u0026nbsp;1). All included patients were treated without systemic antibiotics. Patients with a follow-up period of less than 3 months and those who underwent systemic antibiotic treatment for any reason were excluded. Demographic characteristics including age at the time of diagnosis were recorded.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eAssessment and follow-up\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eAt every follow-up visit, the eyelids, conjunctiva, and corneas of the patients were examined under a slit-lamp biomicroscope with fluorescein staining. The presence of dermatological rosacea, corneal involvement, corneal neovascularisation, phlyctenulosis, and bilateral eye involvement was recorded. Corneal and conjunctival erosions were assessed using the Oxford staining score (0\\u0026ndash;5) following fluorescein staining with a fluorescein dye paper.(10) Blepharitis was graded on a scale from 0 (normal) to 4 (severe) using the Efron grading scale for contact lens complications.(11) Lid margin vascularity was graded on the scale from 0 (no findings) to 3 (severe telangiectasia or redness).(12)\\u003c/p\\u003e\\u003cp\\u003eAs an acute therapy, patients with PBKC were treated with topical antibiotics (0.5% levofloxacin hydrate, 0.3% tobramycin, or 0.5% moxifloxacin hydrochloride) and topical steroids (0.1% fluorometholone or 0.5% loteprednol etabonate, depending on the severity of PBKC) four times a day for less than 2 months. Systemic steroids were administered in some patients with severe corneal pathology. After active inflammation resolved, all patients were instructed to maintain lid hygiene using a tea tree oil-containing lid scrub (OCuSOFT Oust Demodex TTOMAX, Rosenberg, TX). Additionally, the patients were started on topical immune-modulating drugs, such as 0.05% cyclosporine, 0.1% cyclosporine, or 0.03% tacrolimus ointment mixed 1:1 with artificial tear ophthalmic ointment, for chronic disease control. These treatments were gradually tapered. The lid hygiene was maintained until the end of the treatment period (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003eTreatment strategy for pediatric blepharokeratoconjunctivitis\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"2\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eRegimen type\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eComponent\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e1. Regimens for active inflammation control\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eTopical antibiotics and steroids\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eOral steroids in vision-threatening cases\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e2. Regimens for chronic disease control\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eTea tree oil-containing lid scrub, twice daily\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eTopical cyclosporin 0.05% or topical cyclosporin 0.1% \\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eor topical tacrolimus (ointment) 0.03%: artificial tear ointment 1:1 mix\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eStatistics\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe changes in Oxford staining score, blepharitis grading scale score, and lid margin vascularity grade were analysed using a mixed-effects model to account for missing data. All statistical analyses were performed using SPSS version 21.0 (SPSS Inc., Chicago, IL, USA) and Prism 8, GraphPad software (San Diego, USA). A P-value of \\u0026lt;\\u0026thinsp;0.05 was considered significant.\\u003c/p\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cp\\u003e\\u003cb\\u003ePatient characteristics\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eOverall, 21 patients were included. The demographic and clinical features of PBKC patient are summarised in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e, and detailed data for each patient are provided in Supplemental Table\\u0026nbsp;1. The mean age at the first visit was 10.71 years (range: 2\\u0026ndash;17 years), and the mean follow-up period was 10.2 months (range: 2\\u0026ndash;20 months). Overall, 15 patients (71%) were female. A total of 9 patients (43%) had bilateral PBKC, and 12 (57%) patients had a history of chalazia. None of the patients had a history of dermatological rosacea. Fifteen patients (71%) had new corneal vessels, and 6 patients (29%) had corneal phlyctens.\\u003c/p\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003eSummary of characteristics of the patients with pediatric blepharokeratoconjunctivitis\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"12\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c9\\\" colnum=\\\"9\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c10\\\" colnum=\\\"10\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c11\\\" colnum=\\\"11\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c12\\\" colnum=\\\"12\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eN\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eMean age (years)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c4\\\" namest=\\\"c3\\\"\\u003e\\u003cp\\u003eMean F/U duration (months)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eFemale\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eBilateral\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003eHistory of chalazia\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003eDermatologic rosacea\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003eMeibomian gland abnormality\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003eCorneal infiltrates\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003eCorneal NV\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003ePhlycten type\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e21\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e10.71\\u003c/p\\u003e\\u003cp\\u003e(2\\u0026ndash;17)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e10.24\\u003c/p\\u003e\\u003cp\\u003e(3\\u0026ndash;20)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e\\u003cp\\u003e71%\\u003c/p\\u003e\\u003cp\\u003e(15/21)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e43%\\u003c/p\\u003e\\u003cp\\u003e(9/21)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e57%\\u003c/p\\u003e\\u003cp\\u003e(12/21)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e0%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e100%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e100%\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003e71%\\u003c/p\\u003e\\u003cp\\u003e(15/21)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003e29%\\u003c/p\\u003e\\u003cp\\u003e(6/21)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003ctfoot\\u003e\\u003ctr\\u003e\\u003ctd colspan=\\\"12\\\"\\u003eAbbreviations: F/U, follow up; NV, neovascularization\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tfoot\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eChange in erosions, blepharitis, and lid margin vascularity\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe changes in Oxford staining score, blepharitis grading scale score, and lid margin vascularity grade of the PBKC patients are shown in Figs.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. At all-time points, all three scores were significantly lower than baseline. (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001 for all). This indicated that PBKC was effectively controlled with lid scrubs and topical ocular therapies, without the need for systemic antibiotics. Furthermore, keratitis and blepharitis associated with PBKC improved over time with long-term maintenance therapy. The representative photographs of eyelid changes in patients with PBKC during treatment are shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e (A-C) and Supplemental Fig.\\u0026nbsp;2. Blepharitis and meibomitis of PBKC have chronic features that change slowly over time, and it is difficult to evaluate their improvement and deterioration. However, a comparison of the serial photographs revealed that most patients showed improvement in blepharitis and meibomitis.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eChange in corneal phlyctenulosis\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eRepresentative photographs of the changes in corneal phlyctenulosis in patients with PBKC during treatment are presented in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e (D-F) and Supplemental Fig.\\u0026nbsp;3. Most cases of corneal phlyctenulosis stabilised with topical antibiotics and steroids within 1 month and resolved with minimal residual signs when managed with the chronic disease control regimens described in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. Recurrence occurred in two patients who did not adhere well to treatment; however, those who followed the medication regimen experienced no significant recurrence or complications.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eChange in steroid use in combination with chronic disease control regimens\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe changes in the medications used during the follow-up of patients with PBKC are shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e. In this analysis, \\u0026lsquo;steroid use\\u0026rsquo; was defined as regular steroid use under physician guidance. During the follow-up period, the percentage of eyes receiving topical steroid treatment decreased from 71% at 1 month to 14% at 3 months and to 0% at 6 months. After 9 months, only 2 patients restarted steroid treatment, and these patients had poor adherence to chronic disease control regimens. One 14-year-old boy (Case No. 5 in Supplemental Table\\u0026nbsp;1), who had previously been treated for phlyctenulosis, developed recurrence at month 9 of treatment owing to poor treatment compliance. The patient required short-term oral steroids to control the recurrent disease. The other patient was a 12-year-old boy (Case No. 10 in Supplemental Table\\u0026nbsp;1) who did not visit the clinic on the scheduled date and did not take his medications regularly. He required topical steroids and had to use them often until the last visit.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eThis study examined the clinical outcomes of patients with PBKC who were not treated with systemic antibiotics. The patients with PBKC were managed using topical antibiotics and steroids during the acute phase, followed by a tea tree oil-containing lid cleaner and a topical immunomodulating agent for chronic disease control. Using this approach, we were able to effectively control PBKC with minimal recurrence, and the blepharitis improved over time. Clinically significant reactivation was observed only in patients with poor treatment compliance.\\u003c/p\\u003e\\u003cp\\u003ePBKC is one of the most neglected eye diseases despite its potential to cause permanent vision-threatening sequelae.(13) There had been no precise definition of this condition, leading to the use of various terms such as meibomitis-related keratoconjunctivitis, pediatric ocular rosacea, phlyctenular keratitis, and childhood blepharokeratoconjunctivitis.(14) Fortunately, through the efforts of experts, the condition has been formally named PBKC and classified as PBKC and PBKC suspect.(5) As PBKC is often accompanied by inflammatory meibomitis, many clinicians may misdiagnose it as pediatric meibomian gland dysfunction (MGD). However, MGD is primarily a causative condition of evaporative dry eye resulting from chronic obstruction of the meibomian glands.(15) In contrast, PBKC exhibits characteristics that are more aligned with inflammatory keratitis than dry eye disease. Therefore, clinicians should consider these two conditions distinct disease entities.\\u003c/p\\u003e\\u003cp\\u003eMeibomitis is one of the main triggering factors in the pathogenesis of PBKC, and its possible causes include \\u003cem\\u003ePropionibacterium acnes\\u003c/em\\u003e, Staphylococci, and \\u003cem\\u003eDemodex\\u003c/em\\u003e mites.(14) Suzuki et al. performed both aerobic and anaerobic bacterial cultures of meibum from patients with PBKC and found that \\u003cem\\u003eP. acnes\\u003c/em\\u003e may be involved in meibomitis.(16, 17) \\u003cem\\u003ePropionibacterium acnes\\u003c/em\\u003e has long been known to cause inflammation. It can induce a delayed-type hypersensitivity response similar to that of \\u003cem\\u003eMycobacterium tuberculosis\\u003c/em\\u003e, which is thought to be responsible for phlyctenular keratitis.(18\\u0026ndash;20) Staphylococcus, one of the most common microorganisms found on the eyelids and conjunctiva, can cause blepharitis and meibomitis, leading to marginal keratitis.(21, 22) In addition, \\u003cem\\u003eDemodex\\u003c/em\\u003e mites are closely associated with blepharitis.(23),(24) These microorganisms are believed to play significant roles in the pathogenesis of PBKC. Consequently, antibiotics are considered an important component in the treatment of PBKC, and long-term systemic oral antibiotic use is commonly employed to manage the disease and prevent recurrence.(14) However, the range of antibiotics suitable for pediatric patients is limited, and prolonged oral administration is challenging. Given the uncertainty regarding whether these microorganisms represent infections or infestations, we hypothesised that topical treatment alone could provide some level of control. Therefore, this study examined whether PBKC could be effectively controlled without the need for systemic antibiotic therapy.\\u003c/p\\u003e\\u003cp\\u003eBlepharitis and meibomitis have chronic courses that evolve slowly over time, and there is no objective indicator to assess disease severity, particularly in pediatric patients. It was difficult to assess the progression of blepharitis at each visit; however, by collecting and comparing photographs over time, we were able to confirm that improvement was achieved with chronic disease control regimens without the use of systemic antibiotics (Figs.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eA\\u0026ndash;C). Corneal phlyctenulosis, which typically results from delayed hypersensitivity, is a severe form of keratitis. Corneal phlyctenulosis in patients with PBKC initially appeared to be resistant to treatment and may leave permanent sequelae. However, as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eD\\u0026ndash;F, corneal phlyctenulosis can completely resolve with appropriate treatment, with minimal recurrence.\\u003c/p\\u003e\\u003cp\\u003eWe recommended the use of tea-tree oil-containing lid scrub agents owing to their antibacterial and anti-demodex properties. Tea tree oil is a volatile essential oil derived from the Australian native plant \\u003cem\\u003eMelaleuca alternifolia\\u003c/em\\u003e and is incorporated as an active ingredient in many topical formulations used to treat cutaneous infections.(25) Tea tree oil is well known for its effectiveness against the demodex mite.(26, 27) In addition, tea tree oil has sufficient antibacterial effects to target \\u003cem\\u003eP. acnes\\u003c/em\\u003e and Staphylococci, which are implicated in the development of PBKC.(28, 29) Blepharitis and meibomitis associated with PBKC differ from meibomian gland dysfunction owing to the involvement of microorganisms, making tea tree oil-containing lid scrubs an important component in the treatment of PBKC.\\u003c/p\\u003e\\u003cp\\u003eCyclosporine and tacrolimus are calcineurin inhibitors that are used to treat various inflammatory conditions of the ocular surface. Notably, tacrolimus has 10\\u0026ndash;100 times greater immunosuppressive potency than cyclosporine,(30) and its therapeutic effects on PBKC have been reported before.(31, 32) Although the exact pathogenesis of PBKC has not yet been fully elucidated, calcineurin inhibitors typically suppress T cell function, suggesting that delayed-type hypersensitivity may play a key role.(30)\\u003c/p\\u003e\\u003cp\\u003eThis study has several limitations. It was conducted retrospectively, meaning that there was no control group, making it difficult to determine the necessity of systemic antibiotics in patients with PBKC. PBKC is relatively rare and primarily affects children, posing challenges in conducting clinical trials. However, the recent establishment of a formal definition of PBKC marks an important first step toward clarifying this disease. If we can establish objective descriptions and scaled measurements for disease characteristics such as the severity of meibomitis, blepharitis, and phlyctenulosis, more definitive conclusions could be drawn, even in retrospective studies.\\u003c/p\\u003e\\u003cp\\u003eIn conclusion, PBKC can be effectively controlled with lid scrubs and topical ocular therapies without the need for long-term systemic antibiotics. Further studies, well-designed clinical trials in particular, are needed to establish precise and effective treatment strategies.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003ePrecis\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study demonstrates effective control of pediatric blepharokeratoconjunctivitis (PBKC) using lid scrubs and topical therapies without systemic antibiotics while also highlighting that long-term maintenance therapy improves keratitis and blepharitis associated with PBKC.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis retrospective observational case study was approved by the Institutional Review Board of Ajou University Hospital (AJOUIRB-DB-2022-311) and was conducted in accordance with the principles of the Declaration of Helsinki.\\u0026nbsp;The requirement for informed consent was waived by the IRB as the study involved a retrospective review of medical records, for which obtaining consent from each participant was impractical. Furthermore, the study was classified as minimal risk, with no anticipated adverse effects on the safety, rights, or welfare of the participants.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll authors have reviewed the manuscript and provided their consent for publication.\\u003c/p\\u003e\\n\\u003cp\\u003eNo identifiable personal data are included in this manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no proprietary or financial interests in any materials or methods mentioned in this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was supported by the Basic Science Research Program (NRF-2022R1C1C1007243) of the National Research Foundation.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026apos; contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eY.J.C. designed the project, and H.P. and Y.J.C. analysed the results. H.P. and Y.J.C. wrote the manuscript. H.P. and Y.J.C. revised the manuscript critically. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of this work.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors thank Editage for English language editing.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eHamada S, Khan I, Denniston AK, Rauz S. Childhood blepharokeratoconjunctivitis: characterising a severe phenotype in white adolescents. The British journal of ophthalmology. 2012;96(7):949-55.\\u003c/li\\u003e\\n\\u003cli\\u003eRodriguez-Garcia A, Gonzalez-Godinez S, Lopez-Rubio S. Blepharokeratoconjunctivitis in childhood: corneal involvement and visual outcome. Eye. 2016;30(3):438-46.\\u003c/li\\u003e\\n\\u003cli\\u003eMoon J, Lee J, Kim MK, Hyon JY, Jeon HS, Oh JY. Clinical Characteristics and Therapeutic Outcomes of Pediatric Blepharokeratoconjunctivitis. Cornea. 2023;42(5):578-83.\\u003c/li\\u003e\\n\\u003cli\\u003eGupta N, Dhawan A, Beri S, D\\u0026apos;Souza P. Clinical spectrum of pediatric blepharokeratoconjunctivitis. J AAPOS. 2010;14(6):527-9.\\u003c/li\\u003e\\n\\u003cli\\u003eMorales-Mancillas NR, Velazquez-Valenzuela F, Kinoshita S, Suzuki T, Dahlmann-Noor AH, Dart JKG, et al. Definition and Diagnostic Criteria for Pediatric Blepharokeratoconjunctivitis. JAMA ophthalmology. 2024;142(1):39-47.\\u003c/li\\u003e\\n\\u003cli\\u003eSuzuki T. Inflamed Obstructive Meibomian Gland Dysfunction Causes Ocular Surface Inflammation. Investigative ophthalmology \\u0026amp; visual science. 2018;59(14):DES94-DES101.\\u003c/li\\u003e\\n\\u003cli\\u003eOrtiz-Morales G, Morales-Mancillas NR, Paez-Garza JH, Rodriguez-Garcia A. Letter Regarding: Clinical Characteristics and Therapeutic Outcomes of Pediatric Blepharokeratoconjunctivitis. Cornea. 2023;42(6):e10-e1.\\u003c/li\\u003e\\n\\u003cli\\u003eRousta ST. Pediatric blepharokeratoconjunctivitis: is there a \\u0026apos;right\\u0026apos; treatment? Current opinion in ophthalmology. 2017;28(5):449-53.\\u003c/li\\u003e\\n\\u003cli\\u003eCetinkaya A, Akova YA. Pediatric ocular acne rosacea: long-term treatment with systemic antibiotics. American journal of ophthalmology. 2006;142(5):816-21.\\u003c/li\\u003e\\n\\u003cli\\u003eBron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003;22(7):640-50.\\u003c/li\\u003e\\n\\u003cli\\u003eEfron Grading Scales for Contact Lens Complications (\\u003cem\\u003eMillennium edition\\u003c/em\\u003e) [Internet]. Butterworth-Heinemann. 2000. Available from: https://eprints.qut.edu.au/11857/1/11857a.pdf.\\u003c/li\\u003e\\n\\u003cli\\u003eArita R, Minoura I, Morishige N, Shirakawa R, Fukuoka S, Asai K, et al. Development of Definitive and Reliable Grading Scales for Meibomian Gland Dysfunction. American journal of ophthalmology. 2016;169:125-37.\\u003c/li\\u003e\\n\\u003cli\\u003eTeo L, Mehta JS, Htoon HM, Tan DT. Severity of pediatric blepharokeratoconjunctivitis in Asian eyes. American journal of ophthalmology. 2012;153(3):564-70 e1.\\u003c/li\\u003e\\n\\u003cli\\u003eSuzuki T, Teramukai S, Kinoshita S. Meibomian glands and ocular surface inflammation. The ocular surface. 2015;13(2):133-49.\\u003c/li\\u003e\\n\\u003cli\\u003eNelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, et al. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Investigative ophthalmology \\u0026amp; visual science. 2011;52(4):1930-7.\\u003c/li\\u003e\\n\\u003cli\\u003eSuzuki T, Mitsuishi Y, Sano Y, Yokoi N, Kinoshita S. Phlyctenular keratitis associated with meibomitis in young patients. American journal of ophthalmology. 2005;140(1):77-82.\\u003c/li\\u003e\\n\\u003cli\\u003eSuzuki T. Meibomitis-related keratoconjunctivitis: implications and clinical significance of meibomian gland inflammation. Cornea. 2012;31 Suppl 1:S41-4.\\u003c/li\\u003e\\n\\u003cli\\u003eWebster GF, Leyden JJ. Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes. Inflammation. 1980;4(3):261-9.\\u003c/li\\u003e\\n\\u003cli\\u003eWebster GF, Leyden JJ, Norman ME, Nilsson UR. Complement activation in acne vulgaris: in vitro studies with Propionibacterium acnes and Propionibacterium granulosum. Infection and immunity. 1978;22(2):523-9.\\u003c/li\\u003e\\n\\u003cli\\u003eSuzuki T, Sano Y, Sasaki O, Kinoshita S. Ocular surface inflammation induced by Propionibacterium acnes. Cornea. 2002;21(8):812-7.\\u003c/li\\u003e\\n\\u003cli\\u003eDougherty JM, McCulley JP. Comparative bacteriology of chronic blepharitis. The British journal of ophthalmology. 1984;68(8):524-8.\\u003c/li\\u003e\\n\\u003cli\\u003eDougherty JM, McCulley JP. Bacterial lipases and chronic blepharitis. Investigative ophthalmology \\u0026amp; visual science. 1986;27(4):486-91.\\u003c/li\\u003e\\n\\u003cli\\u003eCoston TO. Demodex folliculorum blepharitis. Transactions of the American Ophthalmological Society. 1967;65:361-92.\\u003c/li\\u003e\\n\\u003cli\\u003eLiang L, Ding X, Tseng SC. High prevalence of demodex brevis infestation in chalazia. American journal of ophthalmology. 2014;157(2):342-8 e1.\\u003c/li\\u003e\\n\\u003cli\\u003eCarson CF, Hammer KA, Riley TV. Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other medicinal properties. Clinical microbiology reviews. 2006;19(1):50-62.\\u003c/li\\u003e\\n\\u003cli\\u003eGao YY, Di Pascuale MA, Li W, Baradaran-Rafii A, Elizondo A, Kuo CL, et al. In vitro and in vivo killing of ocular Demodex by tea tree oil. The British journal of ophthalmology. 2005;89(11):1468-73.\\u003c/li\\u003e\\n\\u003cli\\u003eGao YY, Di Pascuale MA, Elizondo A, Tseng SC. Clinical treatment of ocular demodecosis by lid scrub with tea tree oil. Cornea. 2007;26(2):136-43.\\u003c/li\\u003e\\n\\u003cli\\u003eRaman A, Weir U, Bloomfield SF. Antimicrobial effects of tea-tree oil and its major components on Staphylococcus aureus, Staph. epidermidis and Propionibacterium acnes. Lett Appl Microbiol. 1995;21(4):242-5.\\u003c/li\\u003e\\n\\u003cli\\u003eChristoph F, Kaulfers PM, Stahl-Biskup E. A comparative study of the in vitro antimicrobial activity of tea tree oils s.l. with special reference to the activity of beta-triketones. Planta Med. 2000;66(6):556-60.\\u003c/li\\u003e\\n\\u003cli\\u003eKino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo). 1987;40(9):1256-65.\\u003c/li\\u003e\\n\\u003cli\\u003eKymionis GD, Kankariya VP, Kontadakis GA. Tacrolimus ointment 0.03% for treatment of refractory childhood phlyctenular keratoconjunctivitis. Cornea. 2012;31(8):950-2.\\u003c/li\\u003e\\n\\u003cli\\u003eYoon CH, Kim MK, Oh JY. Topical Tacrolimus 0.03% for Maintenance Therapy in Steroid-Dependent, Recurrent Phlyctenular Keratoconjunctivitis. Cornea. 2018;37(2):168-71.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Blepharokeratoconjunctivitis, Meibomitis, blepharitis, phlyctenulosis, pediatric\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7154264/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7154264/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003ePurpose\\u003c/h2\\u003e\\u003cp\\u003eThe optimal treatment of pediatric blepharokeratoconjunctivitis (PBKC) is not well established, and systemic antibiotic therapy is considered an important component of its management. This study aimed to report the therapeutic outcomes of PBKC in the absence of long-term systemic antibiotic therapy.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e\\u003cp\\u003eThis retrospective case series included patients with PBKC aged\\u0026thinsp;\\u0026lt;\\u0026thinsp;18 years who visited Ajou University Medical Center between May 2020 and July 2022. The patients were treated with lid scrubs and topical ocular therapies. We excluded those with less than 3 months of follow-up or systemic antibiotic use. Based on the severity of PBKC, treatments included lid scrubs, topical antibiotics, steroids, and immunomodulatory drugs. Clinical characteristics and disease flare-ups were monitored.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e\\u003cp\\u003eOf the 34 patients identified, 21 patients were included. Overall, 2 of the excluded patients used systemic antibiotics, and 11 patients had less than 3 months of follow-up. The mean age was 10.7 years, and the mean follow-up duration was 10.24 months. The Oxford staining score, blepharitis grading scale score, and lid margin telangiectasia grade improved with treatment. In total, 2/21 patients (14%) experienced flare-ups during the follow-up period; these were controlled with topical antibiotics and steroids within 1 month.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e\\u003cp\\u003ePBKC can be controlled with lid scrubs and topical ocular therapies without long-term systemic antibiotic therapy. Additional therapeutic studies and clinical trials are required to establish more effective treatment strategies.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Long-term treatment outcomes of pediatric blepharokeratoconjunctivitis without systemic antibiotics\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-08-27 06:54:05\",\"doi\":\"10.21203/rs.3.rs-7154264/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"8c8ded61-35e6-456d-90e2-3b1dd9d1a9fe\",\"owner\":[],\"postedDate\":\"August 27th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-10-14T06:53:28+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-08-27 06:54:05\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7154264\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7154264\",\"identity\":\"rs-7154264\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}