A Review of Imaging Biomarkers of the Ocular Surface

Abstract

A biomarker is a “characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.” Recently, calls for biomarkers for ocular surface diseases have increased, and advancements in imaging technologies have aided in allowing imaging biomarkers to serve as a potential solution for this need. This review focuses on the state of imaging biomarkers for ocular surface diseases, specifically non-invasive tear break-up time (NIBUT), tear meniscus measurement and corneal epithelial thickness with anterior segment optical coherence tomography (OCT), meibomian gland morphology with infrared meibography and in vivo confocal microscopy (IVCM), ocular redness with grading scales, and cellular corneal immune cells and nerve assessment by IVCM. Extensive literature review was performed for analytical and clinical validation that currently exists for potential imaging biomarkers. Our summary suggests that the reported analytical and clinical validation state for potential imaging biomarkers is broad, with some having good to excellent intra- and intergrader agreement to date. Examples of these include NIBUT for dry eye disease, ocular redness grading scales, and detection of corneal immune cells by IVCM for grading and monitoring inflammation. Further examples are nerve assessment by IVCM for monitoring severity of diabetes mellitus and neurotrophic keratitis, and corneal epithelial thickness assessment with anterior segment OCT for the diagnosis of early keratoconus. However, additional analytical validation for these biomarkers is required before clinical application as a biomarker.

Comparison of Different Types of Corneal Foreign Bodies Using Anterior Segment Optical Coherence Tomography: A Prospective Observational Study

“…AS-OCT clearly showed the fine structure of the cornea [15][16][17]. e presence of a FB damages the consistency of the corneal structure, which provides the basis for the diagnosis of a FB.…”

Objective Imaging Diagnostics for Dry Eye Disease

“…Moreover, the fluorescein TBUT is unable to simultaneously evaluate the tear break-up across the entire corneal surface [10]. e noninvasive TBUT (NIBUT) was developed to overcome these limitations [10,11]. Instead of using fluorescein dye instillation, the NIBUT measurement involves application of topographic systems to evaluate changes in a regularly patterned image projected onto the tear film that reflects compromised tear film integrity [11,13].…”

“…Anterior segment optical coherence tomography (AS-OCT) produces cross-sectional images of anterior segment structures by low-coherence interferometry [10,20]. e technique enables measurement of tear meniscus parameters important for the diagnosis and monitoring of DED [16,[21][22][23][24][25][26], such as the tear meniscus height (TMH) and tear meniscus area (TMA) [10,20,27], without reflex tearing due to its noncontact nature and rapid image acquisition [11,27].…”

“…Nagahara et al [38] showed that the TMH decreased with CL wear and increased after the instillation of diquafosol sodium. Although the TMH and TMA measured using AS-OCT may be valuable biomarkers for DED [11], factors including the time-from-blink, palpebral aperture, presence of conjunctivochalasis, and lid length should be considered in the interpretation of these tear meniscus measurements [39].…”

“…Among various grading scales proposed for MG dropout [76], the Gestalt grading scale and meiboscale were recommended by the MGD Workshop [74,75]. In the Gestalt grading scale, grading of each lid is performed on a scale from 1 to 4, based on the ratio of partial glands as follows [11]: grade 1 � no partial glands; grade 2 � less than 25% partial glands; grade 3 � 25% to 75% partial glands; and grade 4 � greater than 75% partial glands [11]. In the meiboscale, each lid is graded based on the ratio of MG dropout: grade 0 � no loss of MGs; grade 1 � area loss ≤ 25%; grade 2 � area loss ≤ 50%; grade 3 � area loss ≤ 75%; and grade 4: area loss ≤ 100% [77].…”