College of Optometry, University of Houston, Houston, Texas.
Alcon Laboratories Inc, Fort Worth, Texas.
Optom Vis Sci. 2024 Jul 1;101(7):485-492. doi: 10.1097/OPX.0000000000002168. Epub 2024 Aug 5.
Parkinson's disease symptoms mostly manifest after significant and irreversible neuropathology. Hence, there is a need to identify biomarkers that can provide indications of disease before significant neuronal degeneration occurs.
To estimate the difference in the concentration of α-synuclein protein in tears between individuals with Parkinson's disease and healthy controls.
PubMed, Scopus, and Web of Science. The last database search was on December 20, 2023.
Primary prospective studies in humans measuring the level of α-synuclein in tears and clinical outcomes reported using mean or median.
Individuals with Parkinson's disease and healthy controls.
The risk of bias was assessed using the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity. The outcome measure was the difference in tear total and oligomeric α-synuclein. Mean difference (MD) was used to assess the outcome. The certainty of evidence was rated following the Grading of Recommendations Assessment and Development and Evaluation (GRADE) system.
Three hundred twenty-seven Parkinson's disease and 312 healthy control subjects from five studies and 177 Parkinson's disease and 166 healthy control subjects from two studies were included in total α-synuclein levels and oligomeric α-synuclein levels analysis, respectively. Total α-synuclein level was not different between Parkinson's disease and healthy controls (MD = 0.02 ng/mL [95% confidence interval {CI}: 0.00 to 0.05 ng/mL; I2 = 90%; Z = 1.79; p=0.07; number of studies = 5; GRADE rating = very low]). Stratifying the data based on disease duration, total α-synuclein was higher in subjects with Parkinson's disease duration ≥7 years compared with healthy controls (MD = 0.04 ng/mL [95% CI: 0.03 to 0.05 ng/mL; I2 = 0%; Z = 8.24, p<0.00001; number of studies = 2; GRADE rating = low]) but not different between the two groups (MD = -0.12 ng/mL (95% CI: -0.38 to 0.15 ng/mL; I2 = 93%; Z = 0.84, p=0.40; number of studies = 3; GRADE rating = very low]). Oligomeric α-synuclein level was higher in Parkinson's disease compared with controls (MD = 6.50 ng/mL [95% CI: 2.79 to 10.20 ng/mL; I2 = 94%; Z = 3.44; p=0.0006; number of studies = 2; GRADE rating = very low]).
High heterogeneity between studies. Potential sources of heterogeneity could not be explored due to the limited number of studies.
Tear α-synuclein has the potential to be a noninvasive biomarker for Parkinson's disease. Studies are, however, needed to increase certainty in the biomarker and establish how the protein's changes in tears correlate with Parkinson's disease progression and severity.
帕金森病的症状主要在显著且不可逆转的神经病理学之后出现。因此，需要确定能够在发生显著神经元变性之前提供疾病迹象的生物标志物。
评估帕金森病患者和健康对照者泪液中α-突触核蛋白浓度的差异。
PubMed、Scopus 和 Web of Science。最后一次数据库搜索是在 2023 年 12 月 20 日。
主要为前瞻性研究，在人体中测量泪液中α-突触核蛋白的水平，并使用平均值或中位数报告临床结局。
帕金森病患者和健康对照者。
使用纽卡斯尔-渥太华量表评估偏倚风险。使用 I2 统计量估计异质性。结局测量为总和寡聚体α-突触核蛋白的差异。使用均数差值（MD）评估结局。根据 Grading of Recommendations Assessment and Development and Evaluation（GRADE）系统对证据确定性进行评级。
共纳入来自五项研究的 327 名帕金森病患者和 312 名健康对照者，以及两项研究的 177 名帕金森病患者和 166 名健康对照者进行总α-突触核蛋白水平和寡聚体α-突触核蛋白水平分析。帕金森病患者和健康对照者的总α-突触核蛋白水平无差异（MD = 0.02ng/mL [95%置信区间 {CI}：0.00 至 0.05ng/mL；I2 = 90%；Z = 1.79；p=0.07；研究数量 = 5；GRADE 评级 = 极低]）。根据疾病持续时间进行分层后，帕金森病患者中疾病持续时间≥7 年的患者的总α-突触核蛋白水平高于健康对照者（MD = 0.04ng/mL [95% CI：0.03 至 0.05ng/mL；I2 = 0%；Z = 8.24，p<0.00001；研究数量 = 2；GRADE 评级 = 低]），但两组之间无差异（MD = -0.12ng/mL [95% CI：-0.38 至 0.15ng/mL；I2 = 93%；Z = 0.84，p=0.40；研究数量 = 3；GRADE 评级 = 极低]）。帕金森病患者的寡聚体α-突触核蛋白水平高于健康对照者（MD = 6.50ng/mL [95% CI：2.79 至 10.20ng/mL；I2 = 94%；Z = 3.44；p=0.0006；研究数量 = 2；GRADE 评级 = 极低]）。
研究间存在高度异质性。由于研究数量有限，无法探讨潜在的异质性来源。
泪液中的α-突触核蛋白有可能成为帕金森病的非侵入性生物标志物。然而，需要进一步的研究来提高该生物标志物的确定性，并确定其在泪液中的变化与帕金森病的进展和严重程度如何相关。
