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Cover Focus | May/June 2024

Dry Eye Diagnostics

Diagnostic strategies for comprehensive dry eye care.

Our understanding of dry eye disease (DED) has evolved significantly. Historically viewed as a tear film anomaly, DED is now recognized as a comprehensive disorder of the ocular surface system, including the lacrimal glands, meibomian glands, tear film, and corneal and conjunctival epithelial cells. Each plays an integral role in the health of the ocular surface.


The parainflammation phase marks a pivotal transition between normal ocular surface homeostasis and chronic dry eye, which is characterized by persistent inflammation. Parainflammation signals the ocular surface’s attempt to return to a normal state. Although the concept is well established in other areas of ophthalmology, such as macular degeneration, the role of parainflammation in DED is just beginning to be understood.

Current research indicates that macrophages play a significant role during the parainflammation phase, suggesting an immune response attempting to restore equilibrium. Much remains unknown about parainflammation’s specific mechanisms within DED. Recognizing the complexity of DED as a systemic issue of the ocular surface rather than a singular tear film defect is crucial for advancing diagnostic accuracy and improving patient outcomes.


Managing patient expectations is a critical aspect of treating DED, which can significantly decrease quality of life. Many patients present with frustrations from previous consultations where their symptoms were underestimated or misunderstood. It is crucial that we physicians acknowledge the impact of DED, empathize with the patient’s experience, and set realistic expectations about the chronic nature of the condition.

I prioritize speaking with patients to understand their experiences. I find that a patient-centered approach helps identify the most common symptoms they face, such as burning, foreign body sensation, and the frequent need to close their eyes.

Questionnaires such as the Ocular Surface Disease Index are invaluable for screening purposes and research. A single patient’s symptoms, however, can fluctuate throughout the day and on different days. The variability in patients’ symptoms makes accurately capturing the full spectrum of dry eye symptoms a challenge. This underscores the necessity of a more dynamic, conversational approach in everyday clinical settings to truly understand and address the individual needs of patients with DED.


Inflammatory Markers

The degree of inflammation present significantly influences treatment decisions. Current therapeutic approaches to address inflammation may include steroids, topical cyclosporine, or lifitegrast (Xiidra, Novartis), the last of which is not available in Europe.

Matrix metalloproteinase-9 testing (Inflammadry, Quidel) is commonly used to identify inflammation. A binary result indicates the presence or absence of inflammation based on established cut-off levels, but it does not specify the exact level of the matrix metalloproteinase-9 present. Despite the test’s utility, I find that liquid lissamine green staining provides more nuanced information, is a superior marker for daily clinical use, and facilitates more precise diagnostics and tailored treatment approaches.


The term blepharitis encapsulates a variety of conditions affecting the eyelids, particularly ones involving the meibomian glands, which produce the oily layer of the tear film. Meibography is an invaluable tool when a reduction in meibum production is evident. This imaging technique allows us to visualize the structural integrity of the meibomian glands.

Not all types of blepharitis should be treated with lipid-containing artificial tears. Often, blepharitis involves excessive or improperly distributed lipids on the ocular surface, so the primary issue is not a lack of lipids but their inadequate spread.

In cases of blepharitis characterized by decreased lipid production and structural gland abnormalities, however, as revealed with meibography, treatment with lipid-containing artificial tears is appropriate. These specialized formulations can help replenish the deficient lipid layer, thereby improving tear film stability and ocular comfort.

Tear Production

I frequently utilize the Schirmer test to assess tear production. Patients undergo testing without anesthesia and with their eyes closed. This approach minimizes environmental impact and variability, enhancing the test’s reliability compared to the original method developed by Otto Schirmer, MD, which is performed on open eyes. Avoiding anesthesia helps me gauge natural tear production more accurately.

Tear Film Stability

For evaluating tear film stability, the tear film breakup time test is crucial. Fluorescein dye is effective in highlighting breaks in versus thinning of the tear film, providing a clear indication of tear film integrity. The dye illuminates areas where corneal epithelial cells have disrupted tight junctions, allowing water to penetrate, which is indicative of corneal damage.

I also use lissamine green, which stains cells that are damaged or unprotected by the mucin layer. Unlike fluorescein, lissamine green does not permeate the water-soluble areas of the conjunctiva, making the latter dye ideal for identifying damage at the cellular level.

A new liquid lissamine green formulation (Lissafid, Fidia) with a precise dispenser has greatly enhanced diagnostic accuracy in my practice. The product dispenses the exact dosage required for optimal staining, improving the visibility of conditions on the ocular surface such as dry eye, superior limbic keratoconjunctivitis, and blepharitis. Recent studies have demonstrated that lissamine green staining correlates well with the degree of inflammation present on the ocular surface.1

Tear Film Osmolarity Testing

Tear film osmolarity testing indicates the salt concentration within the tear film. Values are typically elevated in DED patients. The currently available tests measure the osmolarity of the tear film meniscus rather than the entire tear film, introducing variability in results.

Factors such as reflex tearing and obstructions in the tear drainage system can artificially alter the tear meniscus, rendering osmolarity readings misleading. Despite these challenges, osmolarity testing can be valuable for initial screening because it offers a straightforward numerical assessment. A comprehensive diagnosis, however, should involve additional tests to assess ocular surface disease (OSD) accurately.


For those of us looking to specialize in DED or, more broadly, OSD, the essential tools include a slit lamp equipped with an imaging system and diagnostic dyes such as fluorescein and liquid lissamine green. These fundamentals, combined with a comprehensive patient history, provide sufficient information to diagnose the majority of cases.

A precise diagnosis not only specifies the nature of the OSD but also determines the presence of inflammation, which is crucial for selecting the appropriate treatment strategy. Understanding these nuances helps us to tailor intervention, improve patient outcomes, and enhance overall treatment efficacy in ocular health management.

The foundation of successful patient management remains rooted in listening attentively when patients describe their symptoms, making accurate diagnoses, and establishing a therapeutic relationship built on understanding and trust.

1. Yang S, Lee HJ, Kim DY, Shin S, Barabino S, Chung SH. The use of conjunctival staining to measure ocular surface inflammation in patients with dry eye. Cornea. 2019;38(6):698-705.

Stefano Barabino, MD, PhD
  • Head of the Ocular Surface and Dry Eye Center, Ospedale L. Sacco-University of Milan, Milan, Italy
  • stefano.barabino@unimi.it
  • Financial disclosure: None