Dawidziuk Aleksander, Butters Emilia, Lindegger Daniel Josef, Foubister Campbell, Chrost Hugo, Wlodarski Michal, Grogan John, Rowicka Paulina A, Bremner Fion, Manohar Sanjay G
Buckinghamshire Healthcare NHS Trust, Aylesbury HP21 8AL, UK.
Solvemed Inc., 16192 Coastal Highway, Lewes, DE 19958, USA.
Diagnostics (Basel). 2025 May 3;15(9):1167. doi: 10.3390/diagnostics15091167.
The pathological changes preceding the onset of Parkinson's disease (PD) commence several decades before motor symptoms manifest, offering a potential window for identifying objective biomarkers for early diagnosis and disease monitoring. Among the primary non-motor features of PD is autonomic dysfunction; however, its precise assessment remains challenging, limiting its viability as a reliable biomarker. Both the pupillary light reflex (PLR) and pupillary unrest are regulated by autonomic pathways suggesting their potential as objective non-invasive indicators of the PD prodromal phase. This review systematically evaluates studies that compare PLR and pupillary unrest in individuals with PD and healthy controls to determine their utility as potential biomarkers of the disease. A systematic search strategy was designed to identify studies reporting PLR and pupillary unrest findings in PD patients. Searches were conducted across three databases (MEDLINE, Embase PsycINFO), supplemented by cross-referencing relevant studies found on Google Scholar. The literature search was last updated on 7 December 2020. Pupillometric parameters that permitted statistical synthesis included maximum constriction velocity (VMax), constriction amplitude (CAmp), and constriction latency (CL). Pooled incidence and effect sizes were determined using a random-effects model with an inverse variance DerSimonian-Laird estimator. The I statistic was used to assess study heterogeneity. When meta-analysis was not feasible, a qualitative analysis was undertaken. The initial search yielded 219 references. Following deduplication and exclusion of ineligible studies, 31 papers were selected for review. Pupillometric data from 11 studies were incorporated into the meta-analysis. Effect sizes for PD patients were significant for VMax -0.92, ( < 0.01), CAmp -0.58, ( 0.05), and CL 0.46, ( 0.05). Measures of pupillary unrest were elevated in PD patients compared to controls, but evidence was limited to two studies. Pupillary constriction in response to light is characterised by reduced speed and amplitude in PD, with effect sizes suggesting potential clinical applicability. However, evidence regarding baseline pupillary variability remains insufficient, underlining the necessity for further research. Pupillary metrics represent a promising avenue for early PD detection, though their clinical utility is constrained by methodological heterogeneity and variations in disease duration among studies.
帕金森病（PD）发病前的病理变化在运动症状出现前几十年就已开始，这为识别用于早期诊断和疾病监测的客观生物标志物提供了一个潜在的窗口。自主神经功能障碍是PD的主要非运动特征之一；然而，对其进行精确评估仍具有挑战性，限制了其作为可靠生物标志物的可行性。瞳孔对光反射（PLR）和瞳孔动荡均受自主神经通路调节，这表明它们有可能作为PD前驱期的客观非侵入性指标。本综述系统评价了比较PD患者与健康对照者的PLR和瞳孔动荡的研究，以确定它们作为该疾病潜在生物标志物的效用。设计了一种系统检索策略，以识别报告PD患者PLR和瞳孔动荡结果的研究。检索在三个数据库（MEDLINE、Embase、PsycINFO）中进行，并通过对谷歌学术上找到的相关研究进行交叉引用加以补充。文献检索于2020年12月7日最后更新。允许进行统计综合的瞳孔测量参数包括最大收缩速度（VMax）、收缩幅度（CAmp）和收缩潜伏期（CL）。采用具有逆方差DerSimonian-Laird估计量的随机效应模型确定合并发病率和效应大小。I统计量用于评估研究的异质性。当荟萃分析不可行时，进行定性分析。初步检索得到219篇参考文献。在进行重复数据删除和排除不合格研究后，选择了31篇论文进行综述。来自11项研究的瞳孔测量数据被纳入荟萃分析。PD患者的效应大小在VMax方面为-0.92（P<0.01），在CAmp方面为-0.58（P<0.05），在CL方面为0.46（P<0.05）。与对照组相比，PD患者的瞳孔动荡测量值升高，但证据仅限于两项研究。PD患者对光的瞳孔收缩表现为速度和幅度降低，效应大小表明其具有潜在的临床适用性。然而，关于基线瞳孔变异性的证据仍然不足，这突出了进一步研究的必要性。瞳孔指标是早期PD检测的一个有前景的途径，尽管它们的临床效用受到方法学异质性和研究中疾病持续时间差异的限制。
