Acera Arantxa, Ibarrondo Oliver, Mateo-Orobia Antonio J, Pereiro Xandra, Abad-García Beatriz, López-Plandolit Silvia, Ruzafa Noelia, Romero María, Blasco-Martínez Alejandro, Rodríguez Francisco D, Duran Juan A, Vecino Elena
Experimental Ophthalmo-Biology Group, Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Barrio Sarriena S/N, Leioa, E-48940, Spain.
IKERBASQUE, Basque Foundation for Science, Bilbao, 48009, Spain.
BMC Ophthalmol. 2025 Sep 1;25(1):496. doi: 10.1186/s12886-025-04315-1.
The tear-film lipid layer (TFLL) constitutes the outermost barrier of the ocular surface, reducing evaporation and stabilising the tear film. In aqueous-deficient dry eye (ADDE) and Meibomian-gland dysfunction (MGD), compositional changes in the TFLL compromise this protective role. The present study was designed to characterise the tear-lipid fingerprints associated with ADDE and MGD, to compare them with those of healthy subjects, and to assess the impact of intense pulsed-light (IPL) therapy on the tear lipidome in MGD.
In a multicentre, prospective, observational-interventional case-control pilot study, 52 participants were enrolled in two phases: a discovery cohort (9 ADDE, 15 MGD, 13 controls) and an independent validation cohort (15 additional subjects). Tear lipids were profiled by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Unsupervised principal-component analysis (PCA) explored global variance; supervised partial least-squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) defined group differences and yielded candidate biomarkers, with model robustness confirmed by permutation testing and CV-ANOVA. MGD participants received IPL at baseline, day 15, and day 45; clinical metrics and tear samples were obtained before and after therapy.
A total of 176 lipid species were identified and quantified in positive- and negative-ion modes (ESI + and ESI-). Supervised PLS-DA clearly separated ADDE, MGD and control samples, while OPLS-DA highlighted 48 lipids that differed significantly among groups (p < 0.05). Both dry-eye subtypes were characterised by a pronounced depletion of lysophospholipids (LPE, LPC, LPG, LPI; fold change < 0.5) and an enrichment of (O-acyl)-ω-hydroxy fatty acids (OAHFA; fold change > 2) relative to controls. Cholesteryl esters (ChE) showed a subtype-specific elevation only in the MGD-versus-control comparison (fold change > 2). Permutation testing and CV-ANOVA confirmed the robustness of the ADDE-versus-MGD discrimination model. Although IPL therapy significantly improved clinical metrics such as tear break-up time and lissamine-green staining, the changes observed in the tear lipid profile were not statistically significant.
Dry-eye subtypes appear to possess discrete lipidomic signatures; consequently, the lipid panel identified here could serve as a set of potential therapeutic targets. The dissociation between clinical improvement and lipidomic stability after IPL indicates that the therapy may benefit the ocular surface through mechanisms other than large-scale remodelling of the tear-film lipid layer, highlighting the need to explore complementary therapeutic pathways.
泪膜脂质层（TFLL）构成眼表的最外层屏障，可减少蒸发并稳定泪膜。在水液缺乏型干眼（ADDE）和睑板腺功能障碍（MGD）中，TFLL的成分变化损害了这一保护作用。本研究旨在表征与ADDE和MGD相关的泪液脂质指纹图谱，将它们与健康受试者的指纹图谱进行比较，并评估强脉冲光（IPL）治疗对MGD患者泪液脂质组的影响。
在一项多中心、前瞻性、观察性-干预性病例对照试点研究中，52名参与者分为两个阶段入组：一个发现队列（9名ADDE患者、15名MGD患者、13名对照）和一个独立验证队列（另外15名受试者）。通过超高效液相色谱-质谱联用仪（UHPLC-MS）对泪液脂质进行分析。无监督主成分分析（PCA）探索总体方差；有监督偏最小二乘判别分析（PLS-DA）和正交PLS-DA（OPLS-DA）确定组间差异并产生候选生物标志物，通过置换检验和CV-ANOVA确认模型的稳健性。MGD参与者在基线、第15天和第45天接受IPL治疗；在治疗前后获取临床指标和泪液样本。
在正离子和负离子模式（ESI +和ESI-）下共鉴定并定量了176种脂质。有监督PLS-DA能清晰区分ADDE、MGD和对照样本，而OPLS-DA突出显示了48种在组间有显著差异的脂质（p < 0.05）。相对于对照，两种干眼亚型的特征均为溶血磷脂（LPE、LPC、LPG、LPI；倍数变化< 0.5）明显减少，以及（O-酰基）-ω-羟基脂肪酸（OAHFA；倍数变化> 2）增加。仅在MGD与对照的比较中，胆固醇酯（ChE）显示出亚型特异性升高（倍数变化> 2）。置换检验和CV-ANOVA证实了ADDE与MGD判别模型的稳健性。尽管IPL治疗显著改善了泪膜破裂时间和丽丝胺绿染色等临床指标，但泪液脂质谱中观察到的变化无统计学意义。
干眼亚型似乎具有不同的脂质组特征；因此，此处鉴定的脂质组可作为一组潜在的治疗靶点。IPL治疗后临床改善与脂质组稳定性之间的分离表明，该治疗可能通过泪膜脂质层大规模重塑以外的机制使眼表受益，这凸显了探索补充治疗途径的必要性。
