Abstract:AIM: To evaluate the diagnostic utility of meibomian gland uneven atrophy (UA) in identifying Demodex infestation among patients with meibomian gland dysfunction (MGD) and to compare its diagnostic performance with that of cylindrical dandruff (CD). METHODS: Patients with MGD were prospectively enrolled and stratified into four groups (n=25/group) based on the presence/absence of CD and UA. Comparative analyses and multivariate adjustments were performed using Demodex detection confirmed by in vivo confocal microscopy and light microscopy. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 100 patients were recruited. The median age was 31.0y (range: 21.0–45.0y; Q1, Q3: 27.0–37.0y), including 29 males and 71 females. Demodex counts per eyelash and positivity rates were highest in the CD+UA+ group, followed by CD+UA−, and CD−UA+, and then CD−UA−. UA was associated with a 5.521-fold increased likelihood of Demodex positivity [95% confidence interval (CI): 2.098–14.531, P=0.001]; CD conferred a 6.460-fold increased risk (95%CI: 2.454–17.002, P<0.001). Incorporating UA status significantly improved model fit (Δχ²=14.096, P<0.001). The areas under the ROC curve (AUC) for CD (in UA–), UA (in CD–), and CD+UA (CD–UA– and CD+UA+) were 0.776, 0.762, and 0.865, respectively. CD and UA demonstrated comparable sensitivity (CD: 87.5%, UA: 86.7%) and specificity (CD: 65.6%, UA: 65.7%), which improved to 90.9% and 82.1%, respectively, when both were combined. CONCLUSION: UA is a significant predictor of Demodex infestation, with diagnostic performance comparable to CD. Combined assessment of CD and UA offers high sensitivity and good specificity, providing a novel and practical tool and substantially reducing misdiagnosis.