The TFOS DEWS III report defines dry eye as a multifactorial, symptomatic disease characterized by a loss of homeostasis of the tear film and ocular surface, where instability, hyperosmolarity, inflammation, and neurosensory abnormalities serve as primary etiological drivers.1,2
Epidemiological data indicates that 58% of the population reports symptoms,3 yet only 17% of Americans have a formal diagnosis.4 While approximately 38 to 40 million Americans are affected, a mere 1.5 million are receiving treatment.5
Diagnostic imaging in dry eye disease
The diagnostic landscape is complicated by a notorious symptom-sign disconnect.6 Patients often exhibit a neuropathic phenotype, reporting debilitating pain despite minimal clinical findings, or a neurotrophic phenotype characterized by advanced damage while remaining asymptomatic.7 Relying on subjective reports or traditional signs alone risks misclassifying nearly 50% of the disease population.4,8
Figure 1: A patient with neurotrophic keratitis (NK) presenting with corneal epitheliopathy and punctate epithelial erosions, confirmed on cobalt blue filter fluorescein exam (Visit 1). Oxervate (cenegermin-bkbj 0.002%), a recombinant human nerve growth factor, was initiated at Week 3 and epithelial healing with near-complete resolution of punctate keratopathy by Week 12.
Figure 1: Bradley A. Daniel, OD, FAAO, FAAOMS, Dipl ABO.
Clinical advantages of non-invasive imaging
Conventional diagnostic tools, such as the Schirmer's test and vital staining, are inherently disruptive and confound the results; the physical introduction of paper strips or chemical dyes alters the baseline biophysics of the tear film, inducing reflex tearing and accelerating tear film breakup.9,10 Furthermore, subjective grading scales suffer from significant inter-examiner variability and poor reproducibility.11
Non-invasive imaging technologies circumvent these limitations by analyzing the ocular surface in its natural homeostatic state. These platforms provide automated, quantifiable metrics that eliminate observer bias, allowing for precise etiological subtyping and objective longitudinal tracking of therapeutic efficacy.
Review of non-invasive imaging technologies
High-speed videokeratoscopy
Commercial platforms such as the OCULUS Keratograph 5M and the Topcon TERA utilize Placido disc reflections to calculate non-invasive tear breakup time (NIBUT).12-14 By tracking dynamic changes and distortions in the reflected mires between blinks, the software maps the precise location and timing of tear film rupture, providing a highly repeatable, automated assessment of tear film stability without the confounding effects of fluorescein.11
A related Topcon platform, the MYAH,15 pairs optical biometry and corneal topography with the same non-invasive dry eye suite (NIBUT, meibography, tear meniscus height, and blink analysis), making Placido-based tear film assessment available on a combined myopia-management and dry eye instrument.
The Topcon TERA further integrates the OSDI-6 symptom questionnaire directly into its automated digital report, aligning the workflow with DEWS III diagnostic methodology,7 and employs a guided-focus acquisition step that reduces focus-related blur, a common source of false-positive gland-dropout readings.13
Infrared meibography
Available as dedicated imagers like the LipiScan (Johnson & Johnson Vision) or integrated into multimodal platforms like the SBM IDRA (SBM Sistemi),16,17 this technology utilizes infrared illumination to capture the morphological structure of the meibomian glands.18 The software quantifies gland dropout, dilation, and tortuosity, increasingly via automated deep-learning segmentation that removes the variability of subjective grading.19,20
While lower lids are routinely imaged, comprehensive assessment requires upper lid evaluation, as the upper tarsus houses more glands and often exhibits the morphological changes most critical to diagnosing evaporative DED.18
Representative quantitative tools include the deep-learning approach of Wang and colleagues (commercialized as OASIS), which segments glands and grades atrophy against the Pult scale in under 3 minutes,8,20 and the MeiboMetrics algorithm (Espansione Group), which reports the length, width, and area of each gland as an exact percentage of gland loss rather than an ordinal 1-to-4 score.8,21
Separately, multimodal infrared meibographers, such as the Antares and Cobra HD (ViewLight) are being extended toward volumetric (“3D”) gland assessment, though dropout measurements are not yet fully standardized across instruments.22
Figure 2: Infrared meibography of the lower eyelids demonstrating a spectrum of meibomian gland atrophy. Image 1 shows advanced gland dropout with near-complete loss of tubular architecture, while Image 2 shows moderate disease with partially preserved but truncated, irregularly-spaced glands. Infrared illumination renders glandular structures as dark tubular elements against the lighter tarsal plate, enabling direct morphological assessment without dye or contact.
Figure 2: Bradley A. Daniel, OD, FAAO, FAAOMS, Dipl ABO.
Tear film interferometry
Instruments such as the LipiView II (Johnson & Johnson Vision) and the LacryDiag (Lumibird Medical) analyze interference patterns generated by light reflecting off the lipid and aqueous interfaces of the tear film, quantifying lipid layer thickness (LLT) on a nanometer scale.23-25
A LLT at or below 60nm is highly specific for lipid deficiency and meibomian gland dysfunction (approaching 90% specificity) and serves as a strong rule-in threshold; its comparatively low sensitivity, however, means a value above this cutoff does not exclude disease.26
Beyond LLT, the LacryDiag functions as an efficiency-oriented hub, acquiring the core DEWS III-recommended battery (interferometry, NIBUT, tear meniscus height, and meibography) in a single rapid automated sequence to support driver-based subclassification in high-volume practices.24
The TEARCHECK (ESW Vision) extends stability assessment with its patented Tear Film Stability Evaluation (TFSE), which quantifies tear-film micro-deformations, the subclinical tremors that precede frank breakup, to flag instability earlier than conventional NIBUT, and pairs this with an Ocular Surface Inflammatory Evaluation (OSIE) that objectively scores inflammation risk.27
In vivo confocal microscopy (IVCM)
The Heidelberg Retinal Tomograph 3 with the Rostock Cornea Module (HRT3/RCM) is the primary commercially available laser-scanning confocal microscope used to provide cellular-level evaluation of the corneal subbasal nerve plexus and dendritic cell density.28
This imaging is instrumental in identifying the full spectrum of neurosensory abnormalities. It can identify microneuromas and decreased nerve fiber density to support a neuropathic driver in patients with a discordant phenotype of severe pain but minimal staining.29
Conversely, IVCM is also diagnostically supportive for neurotrophic keratitis, revealing profound reductions in subbasal nerve density (on the order of a 60% to 80% or greater decrease relative to healthy controls), along with increased nerve tortuosity or nerve loss and squamous metaplasia in patients presenting with severe surface damage but absent corneal sensation.30
Multispectral "Tear Film Imager"
The Tear Film Imager (TFI) by AdOM Advanced Optical Technologies is a novel device utilizing spectral interference to dynamically measure both the muco-aqueous and lipid layers simultaneously, capturing tear film dynamics multiple times per second between blinks with nanometer-level axial resolution.31,32
It provides a reconstruction of tear film kinetics that traditional static tests cannot achieve. Clinicians should note, however, that the TFI is currently registered with the FDA under a Class I exemption and is not cleared for the diagnosis of dry eye disease.31
Optical coherence elastography (OCE)
As an emerging technology transitioning from the laboratory to the clinic, reverberant 3D OCE is currently utilized via custom-built spectral-domain OCT research platforms.33
By analyzing shear wave propagation, OCE maps the biomechanical elasticity of individual corneal layers, providing volumetric assessments of corneal biomechanics under varying intraocular pressures to advance our understanding of the structural impacts of chronic ocular surface disease.33
High-resolution anterior segment imaging
Advanced AS-OCT devices like the ANTERION (Heidelberg Engineering) and the CASIA2 (Tomey) provide cross-sectional, high-resolution imaging to measure tear meniscus height (TMH), volume, and cross-sectional area.34,35 An AS-OCT TMH of ~0.20mm or less indicates aqueous deficiency, consistent with TFOS DEWS diagnostic thresholds, without the reflex tearing induced by paper strips.7,36
High-resolution digital slit-lamp photography complements cross-sectional tomography by capturing the ocular surface in fine detail. It documents the tear meniscus, lid margins, and ocular surface staining at a resolution suited for serial comparison and patient education.
The Haag-Streit BI 900 slit lamp, fitted with the Imaging Set and EyeSuite Imaging software, captured the photographs in Figures 1 and 3.37 The FireFly (Mediworks) is a lower-cost all-in-one system that combines a digital slit-lamp camera with a built-in dry eye suite, including non-invasive tear breakup time, tear meniscus height, and infrared meibography.38
Figure 3: Cobalt blue slit-lamp biomicroscopy with sodium fluorescein staining before and after Vevye (cyclosporine ophthalmic solution 0.1%) treatment. Pre-treatment (left): Diffuse corneal and limbal fluorescein uptake consistent with ocular surface inflammation, chronic lipid layer thinning, and elevated tear film osmolarity. The patient presented with chronic epiphora and ocular burning refractory to conventional therapy.
One-month post-treatment (right): Marked reduction in corneal and limbal fluorescein staining following 1 month of Vevye therapy. Tear film stabilization and restoration of lipid layer integrity observed clinically; tear osmolarity returned to the normal range, consistent with resolution of hyperosmolar stress and reduction of ocular surface inflammatory burden.
Figure 3: Bradley A. Daniel, OD, FAAO, FAAOMS, Dipl ABO.
Dedicated ocular surface analyzers
Several of the platforms above (the Keratograph 5M, TERA, IDRA, LacryDiag, and TEARCHECK) function in practice as multimodal ocular surface analyzers rather than single-metric instruments, and a growing category of standalone devices is purpose-built for non-invasive OSD workup.
The Bruder Ocular Surface Analyzer (BOSA; M&S Technologies) is representative: a single tabletop unit that acquires NIBUT, tear meniscus height, lipid layer interferometry, infrared meibography, ocular redness grading, blepharitis assessment, and blink quality in a rapid, technician-delegated sequence, then reports each metric on a color-coded scale designed for patient education and protocol-driven treatment selection.40
The clinical value of this class lies less in any single measurement than in capturing the full DEWS III-recommended battery in one encounter, so that driver-based subclassification (aqueous deficient, evaporative, mixed, or blink-related) is available before the physician enters the room.
Because automated grading thresholds and normative ranges are manufacturer-specific, longitudinal comparison is most reliable when repeated on the same instrument.
Implementation challenges and solutions
Cost of equipment and ROI
High capital investment is a primary barrier. Approximately 51% of optometric practice owners cite equipment costs as a hurdle, despite 83% expressing interest in providing these services.39 Return on investment (ROI) is generated through increased treatment acceptance.
Showing a patient a 3D rendering of their own meibomian gland dropout can reinforce understanding and compliance and may help support conversion to in-office procedures such as radiofrequency (RF), intense pulsed light (IPL), low-level light therapy (LLLT), and thermal pulsation.41
Staff training requirements
Implementing multimodal platforms requires strategic clinical delegation. Modern devices feature automated eye tracking and capture sequences, allowing technicians to perform the imaging rapidly.
Comprehensive staff training ensures repeatable image quality and efficient patient flow, reserving the doctor's time purely for data interpretation and treatment planning.
Billing and reimbursement strategies
Most advanced OSD imaging is not directly reimbursed by traditional medical insurance. Practices must adopt a transparent self-pay model for premium diagnostics. Bundling imaging costs into comprehensive dry eye evaluation packages or treatment plans is a proven strategy to overcome reimbursement limitations while delivering advanced, subspecialty-level care.
Figure 4: Outline for a clinical workflow for non-invasive ocular surface imaging with the help of a technician.
Figure 4: Illustration courtesy of Bradley A. Daniel, OD, FAAO, FAAOMS, Dipl ABO.
Key takeaways
- Effective OSD management requires a driver-based approach; symptoms serve as the gatekeeper, but objective imaging dictates the targeted therapy.
- Non-invasive imaging preserves the biophysical integrity of the tear film, providing reproducible data without the noise and influence of external agents, such as vital dyes or Schirmer’s strips, that can disrupt normal tear dynamics and induce reflex tearing.
- Bilateral infrared meibography of upper and lower lids is critical for quantifying dropout and directing treatment for evaporative DED.
- Novel technologies like IVCM and the Tear Film Imager provide cellular and nanometer-scale insights into neurosensory dysfunction and tear kinetics.
- Successful integration of advanced imaging usually involves a delegated technician workflow and a self-pay billing model to offset capital equipment costs.
