目的：利用超高效液相色谱串联四极杆-静电场轨道阱高分辨质谱(ultra-high per formance liquid chromatography tandem quadrupole-electrostatic field orbitrap high resolution mass spectrometer, UHPLC- HRMS)代谢组学技术结合机器学习识别与糖尿病视网膜病变(diabetic retinopathy, DR)进展过程中的房水代谢差异，以寻找DR进展相关生物标志物。方法：本研究共纳入78例2型糖尿病(type 2 diabetes mellitus, T2DM)患者以及30名年龄性别匹配健康对照人群。使用UHPLC- HRMS检测所有患者及对照人群房水中的代谢物丰度，结合机器学习筛选T2DM和DR进展相关代谢物标志物并建立预测模型。结果：在校正混杂因素后，与健康人群对比1, 5-脱水山梨醇、硫酸十四烷基酯和N,N,N-三甲基-5-氨基戊酸在T2DM患者中表现出显著差异(均P < 0.05)；而N-乙酰色氨酸、亚油酰胺、油酰胺、棕榈酰胺、戊酸(游离脂肪酸(5:0)和琥珀酸与DR进展显著相关(均P < 0.001)。代谢通路分析表明，“缬氨酸、亮氨酸和异亮氨酸的生物合成”“精氨酸的生物合成”和“半胱氨酸及蛋氨酸代谢”是T2DM差异代谢途径。基于生物标志物的随机森林预测模型显示，差异代谢产物对T2DM和DR进展的预测准确率分别为81.3%和74%。结论：代谢组学结合机器学习方法有效揭示了T2DM及与DR进展相关的代谢特征，亚油酰胺和油酰胺有望成为DR进展的生物标志物，为DR的诊断和个体化治疗提供了新的可能性。

Objective: To identify aqueous humor metabolic profiles associated with the progression of type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR), aiming to discover potential biomarkers for DR progression. Ultra-high performance liquid chromatography tandem quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-HRMS) will be utilized in conjunction with machine learning (ML) for comprehensive analysis. Methods: A total of 78 patients with T2DM and 30 age- and gender-matched healthy controls were included. UHPLC-HRMS was used to identify metabolites in the aqueous humor of all participants. ML was employed to screen for metabolites associated with T2DM and DR progression, and predictive models were established. Results: After adjusting for covariates, 1,5-anhydroglucitol, tetradecyl sulfate, and n,n,n-trimethyl-5-aminovaleric acid identified as significant indicators for T2DM compared to controls (all P < 0.05). N-acetyltryptophan, linoleamide, oleamide, palmitic amide, valeric acid(FFA(5:0), and succinic acid emerged as predictors for DR progression (all P < 0.001). Metabolic pathway analysis revealed that "valine, leucine and isoleucine biosynthesis", "arginine biosynthesis," and "cysteine and methionine metabolism" were the most enriched pathways for T2DM. Predictive models achieved R² values of 81.3%, and 74% for T2DM and DR progression, respectively. Conclusions: Metabolomic combined with ML effectively uncovered metabolic characteristics associated with T2DM and DR progression. Linoleamide and oleamide represent promising potential biomarkers for DR progression, offering new opportunities for diagnosis and personalized treatment of DR.

目的：观察急性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy，CSC)的自然病程中渗漏点的形态及变化。方法：本研究为前瞻性研究，使用光学相干断层扫描(optical coherence tomography，OCT)观察从发病到发病后5~13个月的CSC患者的渗漏点的OCT形态，测量并计算Hall层、脉络膜全层各自厚度及比值，并进行比较。结果：共20例患者[男14例，女6例，年龄33~59(中位数41)岁]纳入研究。随访时间为5~13个月。在19例患者中观察到微小视网膜色素上皮脱离(pigment epithelium detachment，PED)。1例患者可见视网膜色素上皮(retinal pigment epithelium， RPE)小凸起。在随访期间，仅1例患者的PED完全恢复，其他19例患者在视网膜下液被完全吸收时，RPE和Bruch膜之间仍存在微小分离。渗漏点处的Haller层/脉络膜厚度显著高于中央凹处(初诊时0.806±0.08 vs 0.863±0.06，P=0.003；最后1次随访时为0.801±0.07 vs 0.851±0.06，P=0.004)。结论：本研究观察到在急性CSC患者自然病程中，即使视网膜下液吸收，OCT显示渗漏点处仍存在持续的PED，更厚的Haller层及更薄的内层脉络膜，这些发现为CSC的发病机制提供了更多线索。

Objective: To observe the morphology and changes of leakage points in the natural course of acute central serous chorioretinopathy (CSC). Methods: This study was a prospective study, using optical coherence tomography to observe the OCT morphology of leakage points in CSC patients from onset to 5 to 13 months after onset, measuring the thickness and ratio of Hall layer and the whole choroid, and then compare them. Results: A total of 20 patients were included in the study, including 14 males and 6 females, aged from 33 to 59, with the median being 41 years old. The follow-up time ranged from 5 months to 13 months. Minute retinal pigment epithelial detachments (PED) were observed in 19 patients. A small bulge of retinal pigment epithelium (RPE) was observed in 1 patient. During the follow-up, only one patient totally recovered. Small separation between RPE and Bruch membrane still exit even subretinal fluid were absorbed completely in the other 19 patients. The thickness of Haller layer or choroid at the leakage point was significantly higher than that of the fovea (0.806±0.08 vs 0.863±0.06, P=0.003, at the first visit; 0.801±0.07 vs 0.851±0.06, P=0.004, at the last follow-up). Conclusion: This study observed that in the natural course of acute CSC patients, even if the subretinal fluid was absorbed, OCT still showed that there was persistent PED at the leakage point, thicker Haller layer and thinner inner choroid layer. These findings provided more clues to the pathogenesis of CSC.

目的：观察急性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy，CSC)的自然病程中渗漏点的形态及变化。方法：本研究为前瞻性研究，使用光学相干断层扫描(optical coherence tomography，OCT)观察从发病到发病后5~13个月的CSC患者的渗漏点的OCT形态，测量并计算Hall层、脉络膜全层各自厚度及比值，并进行比较。结果：共20例患者[男14例，女6例，年龄33~59(中位数41)岁]纳入研究。随访时间为5~13个月。在19例患者中观察到微小视网膜色素上皮脱离(pigment epithelium detachment，PED)。1例患者可见视网膜色素上皮(retinal pigment epithelium，RPE)小凸起。在随访期间，仅1例患者的PED完全恢复，其他19例患者在视网膜下液被完全吸收时，RPE和Bruch膜之间仍存在微小分离。渗漏点处的Haller层/脉络膜厚度显著高于中央凹处(初诊时0.806±0.08 vs 0.863±0.06，P=0.003；最后1次随访时为0.801±0.07 vs 0.851±0.06，P=0.004)。结论：本研究观察到在急性CSC患者自然病程中，即使视网膜下液吸收，OCT显示渗漏点处仍存在持续的PED，更厚的Haller层及更薄的内层脉络膜，这些发现为CSC的发病机制提供了更多线索。

Objective: To observe the morphology and changes of leakage points in the natural course of acute central serous chorioretinopathy (CSC). Methods: This study was a prospective study, using optical coherence tomography to observe the OCT morphology of leakage points in CSC patients from onset to 5 to 13 months after onset, measuring the thickness and ratio of Hall layer and the whole choroid, and then compare them. Results: A total of 20 patients were included in the study, including 14 males and 6 females, aged from 33 to 59, with the median being 41 years old. The follow-up time ranged from 5 months to 13 months. Minute retinal pigment epithelial detachments (PED) were observed in 19 patients. A small bulge of retinal pigment epithelium (RPE) was observed in 1 patient. During the follow-up, only one patient totally recovered. Small separation between RPE and Bruch membrane still exit even subretinal fluid were absorbed completely in the other 19 patients. The thickness of Haller layer or choroid at the leakage point was significantly higher than that of the fovea (0.806±0.08 vs 0.863±0.06, P=0.003, at the first visit; 0.801±0.07 vs 0.851±0.06, P=0.004, at the last follow-up). Conclusion: This study observed that in the natural course of acute CSC patients, even if the subretinal fluid was absorbed, OCT still showed that there was persistent PED at the leakage point, thicker Haller layer and thinner inner choroid layer. These findings provided more clues to the pathogenesis of CSC.