{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:24:21Z","timestamp":1755217461308,"version":"3.43.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To develop and validate a novel digital biomarker, the energy curve of the meibomian gland (MG) edge, to assess MG uneven atrophy and aid in diagnosing <jats:italic>Demodex<\/jats:italic> blepharitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective study enrolled 76 dry eye patients (42 with <jats:italic>Demodex<\/jats:italic> blepharitis, 34 controls). Segmentation of upper eyelid meibography images was accomplished via a convolutional neural network (CNN)-based artificial intelligence (AI) model. The lower margin curve of MGs was extracted using an active contour model (Snake) to compute a composite energy value that integrates elastic, curvature, and smoothness energies. Clinical parameters, including non-invasive tear breakup time (NIBUT), lid margin score, and Meiboscore, were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>Demodex<\/jats:italic> group showed shorter NIBUT (median: 2.84 vs. 5.18 s, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and higher lid margin scores (median: 2 vs. 1, <jats:italic>p<\/jats:italic> = 0.002) and Meiboscores (median: 1 vs. 1, <jats:italic>p<\/jats:italic> = 0.009). The <jats:italic>Demodex<\/jats:italic> group also exhibited significantly higher energy curve values than controls (median: 32.44 vs. 11.20, <jats:italic>p<\/jats:italic> &amp;lt; 0.001), reflecting pronounced uneven gland atrophy. Meanwhile, MG density significantly influenced energy curve values (<jats:italic>p<\/jats:italic> = 0.010). After adjusting for MG density, the energy curve demonstrated strong diagnostic accuracy (AUC = 0.897, sensitivity 78.6%, specificity 91.2%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The energy curve quantifies structural irregularities in MGs caused by <jats:italic>Demodex<\/jats:italic> infestation, serving as a non-invasive biomarker for early diagnosis. Its integration with meibography enhances clinical workflows, particularly in resource-limited settings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1627327","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T14:29:53Z","timestamp":1754404193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A new digital biomarker of Demodex blepharitis: energy curve of the meibomian edge"],"prefix":"10.3389","volume":"13","author":[{"given":"Minjia","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kesheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunhui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1007\/s10792-022-02523-y","article-title":"Prevalence of Demodex folliculorum and Demodex brevis in patients with blepharitis and chalazion","volume":"43","author":"Akkucuk","year":"2023","journal-title":"Int. Ophthalmol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1136\/bjophthalmol-2012-303014","article-title":"Objective image analysis of the meibomian gland area","volume":"98","author":"Arita","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/cxo.13123","article-title":"Demodex and eye disease: a review","volume":"104","author":"Bitton","year":"2021","journal-title":"Clin. Exp. Optom."},{"key":"B4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3760\/cma.j.issn.0412-4081.2018.07.004","article-title":"Expert consensus on diagnosis and treatment of demodex blepharitis in China","volume":"54","author":"Branch","year":"2018","journal-title":"Zhonghua Yan Ke Za Zhi."},{"key":"B5","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/ICU.0000000000000168","article-title":"Recent advances on ocular demodex infestation","volume":"26","author":"Cheng","year":"2015","journal-title":"Curr. Opin. Ophthalmol."},{"key":"B6","first-page":"1","article-title":"A novel Meibomian gland morphology analytic system based on a convolutional neural network","author":"Dai Ql","year":"2021","journal-title":"IEEE Access"},{"key":"B7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/s41598-023-50858-y","article-title":"Effects of climate factors and demodex infestation on Meibomian gland dysfunction-associated dry eye diseases","volume":"14","author":"Deng","year":"2024","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"101132","DOI":"10.1016\/j.eclinm.2021.101132","article-title":"Quantitative analysis of morphological and functional features in meibography for meibomian gland dysfunction: diagnosis and grading","volume":"40","author":"Deng","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.18240\/ijo.2024.06.07","article-title":"Factors affecting Meibomian gland area loss in symptomatic adults","volume":"17","author":"Ding","year":"2024","journal-title":"Int. J. Ophthalmol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.clindermatol.2014.02.012","article-title":"Demodex mites","volume":"32","author":"Elston","year":"2014","journal-title":"Clin. Dermatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e000436","DOI":"10.1136\/bmjophth-2020-000436","article-title":"Image based analysis of Meibomian gland dysfunction using conditional generative adversarial neural network","volume":"6","author":"Khan","year":"2021","journal-title":"BMJ Open Ophthalmol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.cyto.2010.08.009","article-title":"Tear cytokines and chemokines in patients with demodex blepharitis","volume":"53","author":"Kim","year":"2011","journal-title":"Cytokine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.survophthal.2024.07.005","article-title":"Advances in artificial intelligence for meibomian gland evaluation: a comprehensive review","volume":"69","author":"Li","year":"2024","journal-title":"Surv. Ophthalmol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1136\/bjophthalmol-2017-310302","article-title":"Significant correlation between Meibomian gland dysfunction and keratitis in young patients with Demodex brevis infestation","volume":"102","author":"Liang","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"P50","DOI":"10.1016\/j.ophtha.2023.12.036","article-title":"Blepharitis preferred practice pattern\u00ae","volume":"131","author":"Lin","year":"2024","journal-title":"Ophthalmology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"934821","DOI":"10.3389\/fphys.2022.934821","article-title":"Uneven index: a digital biomarker to prompt demodex blepharitis based on deep learning","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21037\/tcr-20-1269","article-title":"Clinical value of energy spectrum curves of dual-energy computer tomography May help to predict pathological grading of gastric adenocarcinoma","volume":"10","author":"Lu","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"22","DOI":"10.5120\/ijca2016910808","article-title":"Energy based methods for medical image segmentation","volume":"146","author":"Pamela","year":"2016","journal-title":"Int. J. Comput. Appl."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.4103\/ijo.IJO_3641_20","article-title":"A clinical study on the correlation between demodex infestation and ocular surface changes in patients with Meibomian gland dysfunction","volume":"69","author":"Pan","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ajo.2019.03.007","article-title":"Demodex mite infestation and its associations with tear film and ocular surface parameters in patients with ocular discomfort","volume":"204","author":"Rabensteiner","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.jtos.2022.06.006","article-title":"Automated quantification of Meibomian gland dropout in infrared meibography using deep learning","volume":"26","author":"Saha","year":"2022","journal-title":"Ocul. Surf."},{"key":"B22","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s12886-022-02610-9","article-title":"The correlation between demodex infestation and Meibomian gland dysfunction at different ages","volume":"22","author":"Sun","year":"2022","journal-title":"BMC Ophthalmol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jtos.2022.06.002","article-title":"Latest developments in meibography: a review","volume":"25","author":"Swiderska","year":"2022","journal-title":"Ocul. Surf."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1518154","DOI":"10.3389\/fcell.2024.1518154","article-title":"Meibomian gland alterations in allergic conjunctivitis: insights from a novel quantitative analysis algorithm","volume":"12","author":"Wei","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"592759","DOI":"10.3389\/fmed.2020.592759","article-title":"Association between demodex infestation and ocular surface microbiota in patients with demodex blepharitis","volume":"7","author":"Yan","year":"2020","journal-title":"Front. Med. (Lausanne)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1097\/j.jcrs.0000000000001619","article-title":"Meibomian gland structure and function in patients with demodex blepharitis","volume":"51","author":"Yeu","year":"2025","journal-title":"J. Cataract. Refract Surg."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1097\/ICO.0000000000000533","article-title":"Uneven meibomian gland dropout over the tarsal plate and its correlation with meibomian gland dysfunction","volume":"34","author":"Yin","year":"2015","journal-title":"Cornea."},{"key":"B28","doi-asserted-by":"publisher","first-page":"5085","DOI":"10.3390\/jcm11175085","article-title":"Uneven meibomian gland dropout in patients with meibomian gland dysfunction and demodex infestation","volume":"11","author":"Yu","year":"2022","journal-title":"J. Clin. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.3390\/jcm11092396","article-title":"Meibomian gland density: an effective evaluation index of meibomian gland dysfunction based on deep learning and transfer learning","volume":"11","author":"Zhang","year":"2022","journal-title":"J. Clin. Med."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1627327\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T14:29:56Z","timestamp":1754404196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1627327\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":29,"alternative-id":["10.3389\/fcell.2025.1627327"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1627327","relation":{},"ISSN":["2296-634X"],"issn-type":[{"type":"electronic","value":"2296-634X"}],"subject":[],"published":{"date-parts":[[2025,8,5]]},"article-number":"1627327"}}