Fan Zixin, Yang Shuo, Lu Xiaofeng, Zhang Sifan, Zeng Xianlu, Lin Lin, Yuan Duo, Zeng Jian, Zhang Guoming
Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, Guangdong, China.
New York University, New York, New York, United States.
Invest Ophthalmol Vis Sci. 2025 Jun 2;66(6):61. doi: 10.1167/iovs.66.6.61.
The purpose of this study was to investigate the characteristics of metabolomic profile in the tears from infants with retinopathy of prematurity (ROP) and further define noninvasive biomarkers.
This prospective study included 94 eyes from 47 premature infants. Tear samples from 23 infants with ROP (15 treatment-requiring ones [ROP (t)] and 8 non-treatment-requiring ones [ROP (nt)]) and 24 infants without ROP were collected with Schirmer strips after topical anesthesia. Detailed fundus examination upon pupil dilation were conducted, with data on demographics and birth history recorded. Untargeted tear metabolomic analysis based on ultra-performance liquid chromatography-mass spectrometry was performed.
Adjusted by sex, postmenstrual age, gestational age, and birth weight, among 145 metabolites quantified, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, caffeine, and trehalose were identified to be upregulated in the tears from infants with ROP when compared to those from premature infants with non-ROP, whereas uric acid, dihomo-γ-linolenic acid, nootkatone, pyridoxal, ornithine, 6-keto-prostaglandin F1 alpha, adenosine, and tetrahydrocortisol were downregulated (all adjusted false discovery rate [FDR adj] < 0.05). Nine and one dysregulated metabolites were further found in the ROP (t) and ROP (nt) subgroups, respectively. Some of these metabolites exhibited expression levels correlated with postmenstrual age, gestational age, birth weight, and ROP severity in varying degrees. The dysregulated tear metabolites were fundamentally related to vitamin B6, purine, caffeine, arginine, and starch and sucrose metabolism pathways. The 6-keto-prostaglandin F1 alpha obtained the best performance in classifying premature infants with and without ROP (area under the curve [AUC] of 0.893 [range = 0.800-0.986], P < 0.001).
Dysregulated tear metabolites in ROP exhibited abundance correlated with severity of the disease and might be noninvasive biomarkers that potentially serve as complementary screening tools.
本研究旨在调查早产儿视网膜病变（ROP）患儿泪液代谢组学特征，并进一步确定非侵入性生物标志物。
这项前瞻性研究纳入了47例早产儿的94只眼。对23例ROP患儿（15例需要治疗的患儿[ROP（t）]和8例不需要治疗的患儿[ROP（nt）]）以及24例无ROP的患儿在局部麻醉后用泪液试纸条采集泪液样本。在散瞳后进行详细的眼底检查，并记录人口统计学和出生史数据。基于超高效液相色谱-质谱法进行非靶向泪液代谢组学分析。
在按性别、月经后年龄、胎龄和出生体重进行校正后，在定量的145种代谢物中，与无ROP的早产儿相比，3,5-二叔丁基-4-羟基苯甲醛、咖啡因和海藻糖在ROP患儿的泪液中上调，而尿酸、二高-γ-亚麻酸、诺卡酮、吡哆醛、鸟氨酸、6-酮-前列腺素F1α、腺苷和四氢皮质醇下调（所有校正后的错误发现率[FDR adj]<0.05）。在ROP（t）和ROP（nt）亚组中分别进一步发现9种和1种失调的代谢物。其中一些代谢物的表达水平与月经后年龄、胎龄、出生体重和ROP严重程度在不同程度上相关。泪液中失调的代谢物与维生素B6、嘌呤、咖啡因、精氨酸以及淀粉和蔗糖代谢途径密切相关。6-酮-前列腺素F1α在区分有和无ROP的早产儿方面表现最佳（曲线下面积[AUC]为0.893[范围=0.800-0.986]，P<0.001）。
ROP患儿泪液中失调的代谢物丰度与疾病严重程度相关，可能是非侵入性生物标志物，有望作为补充筛查工具。
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