Tear Fluid Biomarker Profiling: A Review of Multiplex Bead Analysis

Hagan, Suzanne; Tomlinson, Alan

doi:10.1016/j.jtos.2013.04.004

Cited by 48 publications

(42 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…45–47 Inflammatory mediators released in tears have been recognized as one of the key components in ocular surface inflammation that have prominent roles in the pathophysiology of DED. 48 Of the multiple inflammatory biomarkers under investigation, cytokines and chemokines are the most frequently reported and studied in DED.…”

Section: Biomarkers Of Inflammationmentioning

confidence: 99%

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Roy

Wei

Kuklinski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeBiomarkers 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.MethodsThe 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.ResultsSignificant 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.ConclusionsMany 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.OverviewDED 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.

show abstract

Section: Biomarkers Of Inflammationmentioning

confidence: 99%

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Roy

Wei

Kuklinski

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Therefore future studies, including the optimization of standard operating procedures for qPCR, should first be undertaken in order to address this potentially confounding factor. As with tear fluid biomarker analysis [72], it is anticipated that future IC studies comprising larger patient cohorts, more strict stratification of recruited patients, improved assay sensitivities and standardized methodologies will all serve to enhance the diagnosis, monitoring and treatment of disorders of the ocular surface.…”

Section: Resultsmentioning

confidence: 99%

Biomarkers of Ocular Surface Disease Using Impression Cytology

Hagan

2017

Biomark. Med.

Self Cite

View full text Add to dashboard Cite

Impression cytology (IC) is a technique which permits the retrieval of the outermost layer of ocular surface cells via the use of various types of filters. It is a minimally invasive method of evaluating human conjunctival epithelial cell morphology in the diagnosis of dry eye disease, a common and distressing disorder associated with ageing, contact lens wear, autoimmune disorders and refractive (LASIK) surgery. IC may also be utilized in the diagnosis of other ocular diseases, such as keratoconus and thyroid orbitopathy. More recently, IC has been utilized for the subsequent investigation of gene and protein expression of conjunctival cells in order to identify novel diagnostic biomarkers and to further our understanding of the mechanisms underlying ocular surface disease. This review will therefore examine the literature concerning the role of IC in identifying cellular markers of eye disease, systemic diseases with ocular involvement and potential novel therapeutic targets. Impression cytology (IC) is a minimally invasive method of evaluating human ocular surface cells and is considered as the 'gold standard' technique for assessing cell morphology. Introduced by Thatcher et al. [1] and Egbert et al. [2], IC is an easy-to-use technique of directly retrieving (mainly conjunctival) cells, using various filter types which are gently applied to exposed (interpalpebral) conjunctival surfaces. The filters used include cellulose acetate [3], polycarbonate (Biopore, Millipore UK Ltd, Watford, UK) [4], nitrocellulose [5] or polyethersulfone (PES) [6] which are gently applied to exposed (interpalpebral) conjunctival surfaces. Recently, a more standardized tool for IC sampling has been introduced (Figures 1 & 2). The Eyeprim is a new single-use PES filter sampling medical device for retrieval of conjunctival cells (Opia Technologies, France) and a recent study by Lopez-Miguel et al. [7] performed an analysis of this tool versus the traditional IC method (PES). On a cohort of 20 healthy individuals, they extracted and compared RNA from both devices and found no significant differences in the mean yield (p ≥ 0.45), the total RNA amount (μg), or the amount normalized to membrane area [7]. Although an earlier study of the Eyeprim [8], suggested that it recovered more cells than traditional IC, Lopez-Miguel et al. [7] did not observe differences in the RNA collected between this device and PES.Historically, IC has been used to analyze pathological changes to conjunctival cells for indicators of squamous metaplasia in ocular surface disease (OSD) [9]. More recently, however, researchers have used IC to examine specific markers of inflammation, for example, HLA-DR, ICAM-1 and CD8 [10][11][12], and to examine novel biomarkers of dry eye disease (DED). The latter is performed in an attempt to understand the mechanisms underpinning DED pathophysiology and is now feasible, due to vast improvements in the assay sensitivities for gene and protein examination [13]. As a result, IC membranes can be subsequently analyzed using techniq...

show abstract

“…This single-use silicone contact lens is a noninvasive wireless contact lens sensor capable of automatically recording IOP changes for up to 24 h. 11,46,47 The technology uses four circular strain gauges embedded within the contact lens, which are capable of sensing circumferential changes at the limbus. 11,13,14,16,48 Relative variations in IOP can thus be monitored indirectly by virtue of the changes in ocular volume they cause. 11,46,47 The embedded microprocessor and antenna in the contact lens sensor transfer the data wirelessly to an external eyepiece.…”

Section: Semicontinuous Iop Monitoring For Glaucomamentioning

confidence: 99%

“…12Y14 One of the biggest advantages of developing contact lens sensors is it provides a noninvasive alternative to current invasive methods to monitor diseases. 15,16 This overview will highlight the major progress to date in developing contact lens sensors for continuous, semicontinuous, and noncontinuous detection of diseases and several of the key technical and clinical challenges in this field as reported in the peer-reviewed literature. Because of space considerations, although we have extensively discussed peer-reviewed publications, it has not been possible to take into consideration the entire patent literature in this area, which is extensive.…”

mentioning

confidence: 99%

The Use of Contact Lenses as Biosensors

Phan

Subbaraman

Jones

2016

Optometry and Vision Science

View full text Add to dashboard Cite

: The tear film is a complex multilayer film consisting of various proteins, enzymes, and lipids and can express a number of biomarkers in cases of disease. The development of a contact lens sensor presents a noninvasive alternative for the detection and management of various diseases. Recent work has resulted in the commercialization of a device to monitor intraocular pressure for up to 24 h, and there are extensive efforts underway to develop a contact lens sensor capable of continuous glucose tear film monitoring to manage diabetes. This clinical perspective will highlight the major developments within this field and list some of the major challenges that still need to be addressed.

show abstract

Tear Fluid Biomarker Profiling: A Review of Multiplex Bead Analysis

Cited by 48 publications

References 91 publications

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research

Biomarkers of Ocular Surface Disease Using Impression Cytology

The Use of Contact Lenses as Biosensors

Contact Info

Product

Resources

About