Roy Neeta S, Wei Yi, Kuklinski Eric, Asbell Penny A
Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, United States.
Invest Ophthalmol Vis Sci. 2017 May 1;58(6):BIO1-BIO19. doi: 10.1167/iovs.17-21709.
Biomarkers with minimally invasive and reproducible objective metrics provide the key to future paradigm shifts in understanding of the underlying causes of dry eye disease (DED) and approaches to treatment of DED. We review biomarkers and their validity in providing objective metrics for DED clinical research and patient care.
The English-language literature in PubMed primarily over the last decade was surveyed for studies related to identification of biomarkers of DED: (1) inflammation, (2) point-of-care, (3) ocular imaging, and (4) genetics. Relevant studies in each group were individually evaluated for (1) methodological and analytical details, (2) data and concordance with other similar studies, and (3) potential to serve as validated biomarkers with objective metrics.
Significant work has been done to identify biomarkers for DED clinical trials and for patient care. Interstudy variation among studies dealing with the same biomarker type was high. This could be attributed to biologic variations and/or differences in processing, and data analysis. Correlation with other signs and symptoms of DED was not always clear or present.
Many of the biomarkers reviewed show the potential to serve as validated and objective metrics for clinical research and patient care in DED. Interstudy variation for a given biomarker emphasizes the need for detailed reporting of study methodology, including information on subject characteristics, quality control, processing, and analysis methods to optimize development of nonsubjective metrics. Biomarker development offers a rich opportunity to significantly move forward clinical research and patient care in DED.
DED is an unmet medical need - a chronic pain syndrome associated with variable vision that affects quality of life, is common with advancing age, interferes with the comfortable use of contact lenses, and can diminish results of eye surgeries, such as cataract extraction, LASIK, and glaucoma procedures. It is a worldwide medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.
具有微创且可重复的客观指标的生物标志物是未来在理解干眼疾病（DED）潜在病因及治疗方法方面实现范式转变的关键。我们回顾生物标志物及其在为DED临床研究和患者护理提供客观指标方面的有效性。
主要检索了过去十年PubMed上的英文文献，以查找与DED生物标志物识别相关的研究：（1）炎症，（2）即时检测，（3）眼部成像，以及（4）遗传学。对每组中的相关研究分别评估其（1）方法学和分析细节，（2）数据以及与其他类似研究的一致性，（3）作为具有客观指标的经过验证的生物标志物的潜力。
在识别用于DED临床试验和患者护理的生物标志物方面已经开展了大量工作。处理相同生物标志物类型的研究之间的研究间差异很大。这可能归因于生物学变异和/或处理及数据分析方面的差异。与DED的其他体征和症状的相关性并不总是明确或存在的。
许多被回顾的生物标志物显示出作为DED临床研究和患者护理中经过验证的客观指标的潜力。给定生物标志物的研究间差异强调了详细报告研究方法的必要性，包括有关受试者特征、质量控制、处理和分析方法的信息，以优化非主观指标的开发。生物标志物的开发为显著推进DED的临床研究和患者护理提供了丰富的机会。
DED是一种未满足的医疗需求——一种与视力变化相关的慢性疼痛综合征，会影响生活质量，随着年龄增长而常见，干扰隐形眼镜的舒适佩戴，并且会降低眼部手术（如白内障摘除、LASIK和青光眼手术）的效果。它是一项全球性的医学挑战，患病率在8%至50%之间。全球许多临床医生和研究人员都在寻找更好的答案来理解与DED发生和慢性化相关的机制。尽管已经有许多针对DED的临床试验，但在过去十年中几乎没有出现新的治疗方法。生物标志物可能提供所需的突破，将我们对DED的理解提升到一个新水平，并有可能实现基于科学证据的真正个性化医疗的目标。DED的临床试验和研究一直缺乏经过验证的生物标志物以及不够客观和可重复的终点。目前关于生物标志物的工作已经为向前推进奠定了基础。本综述主要强调了已被研究用于DED的眼部生物标志物，讨论了为临床研究提供客观指标的方法学结果，并提出了进一步工作的建议。
