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.

The purpose of this study was to assess projection-resolved optical coherence tomography angiography (PR-OCTA) vessel density (VD) and foveal avascular zone (FAZ) in determining severity within diabetic retinopathy (DR) and their accuracy in identifying highrisk DR patients. METHODS. This was a retrospective study with 72 eyes of 52 DR patients, assessing the VD and FAZ area of the superficial capillary plexus (SCP) and deep vascular plexus (DVP), for both 3 3 3-mm and 6 3 6-mm scans between the DR groups (mild to moderate, severe and proliferative DR [PDR]). For accuracy, the severe and PDR groups were merged, representing the high-risk DR group for receiver operator characteristic analysis. VD of OCTA images with and without PR were compared. RESULTS. In mild to moderate, severe, and PDR groups, there were 31, 21, and 20 eyes, respectively. PR-OCTA improved VD analysis only in the DVP and particularly in advanced DR stages (P ¼ 0.042). In the 3 3 3-mm PR scans, all superficial and deep parameters were significantly different between severe and PDR groups (P 0.020), but only the mean VD of SCP and DVP was also significant between the mild to moderate and severe groups (P 0.007). In the 6 3 6-mm scans, the superficial VD, deep VD, and superficial FAZ were significantly different between the severe and PDR groups (P 0.029). The superficial VD and deep VD of the 3 3 3-mm scans were good parameters for detecting high-risk patients (area under the curve ¼ 0.829 and 0.895, respectively). CONCLUSIONS. PR-OCTA improved VD analysis of DVP. The 3 3 3-mm SCP and DVP VD were the most accurate in detecting high-risk DR.

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