Dry Eye Disease: Diagnosis in the Clinical Setting

Due to the absence of a gold standard test, diagnosing dry eye disease (DED) can present a challenging task. But with the increasing global prevalence of the disease, it is imperative that we focus on early detection and management of DED to alleviate the burden on both clinicians and patients. There are currently several technologically advanced tests that are useful for detecting severe DED cases, but all these tests have limited applicability for intermediate manifestations (1). Nonetheless, a comprehensive assessment of signs and symptoms, along with some common examinations, can be used to accurately diagnose DED in routine clinical scenarios.

Initial triaging and examination
 

Capturing patient history and symptoms

Before diagnosing DED, it is crucial to rule out any conditions that might appear clinically similar to the disease. This can be achieved by asking the patient triage questions, recording a detailed patient history (including severity and duration of ocular symptoms), studying any triggers for symptoms (infection/ulceration), and checking for any presence of systemic diseases, as well as looking at the patient’s past medication history (2).

Questionnaires

For early diagnosis of DED, the use of validated and standardized questionnaires is recommended by the Tear Film and Ocular Surface Society’s Dry Eye Workshop II (TFOS DEWS II) (3). They can easily be filled in by patients and integrating them into outpatient departments can help screen and manage a large patient group efficiently.

Some common questionnaires are outlined below:

• Ocular Surface Disease Index (OSDI): Assesses the frequency of symptoms, environmental triggers, and quality of life related to vision; a score ≥13 indicates DED
• Dry Eye Questionnaire (DEQ-5): Provides information about the frequency, intensity, and impact of common visual disturbances; a score ≥ 6 indicates DED
• Symptom Assessment in Dry Eye (SANDE) and Standard Patient Evaluation of Eye Dryness (SPEED) are also used concurrently with OSDI

Lid examination

During patient counseling, taking note of lid closure (poor in DED), and conducting a detailed lid examination for any inflammation or meibomian gland dysfunction (MGD) is key to initial diagnosis (2). Patients with MGD often exhibit eyelid margin abnormalities, such as thick, blunt eyelid margins (4) or poor gland expressibility (5). A thorough slit-lamp examination is the simplest step towards evaluating dry eye signs through detailed lid, corneal, or conjunctival examination (punctate and superficial corneal erosions), lower tear break-up time, conjunctival hyperemia, conjunctival surface irregularities, and MGD.

Blink assessments

Blink evaluations play an important role in initial assessments. These can be evaluated as incomplete blinks, reduced blink rate or frequency, blink amplitude, blink quality (6), maximum blink Interval, and interblink interval (7). The self-administered blink test requires patients to look at a computer screen and record how long they can avoid blinking before experiencing discomfort. Blink frequency or blink rate refers to the total number of blinks performed in a specified period, typically 10-15 blinks per minute, and is reduced in DED. Blink amplitude is the distance between the eyelid position at the blink onset and the point of eyelid closure during a blink. Low blink amplitude indicates an incomplete blink. Blink quality incorporates blink completeness and blinking mechanisms associated with the optimum functioning of the ocular surface).

Blink evaluations are described as one of the simplest evaluations for DED (as per the outer bronze ring of the Dry Eye Wheel) and as a risk factor for evaporative dry eye (EDE) (8). The Dry Eye Wheel simplifies early approaches to DED evaluation, mitigation, and management. The wheel consists of three rings depicting simple to more complex approaches (as per disease severity) for managing DED, providing clinicians with clues regarding the sub-type.

Ocular protection index

The vicious cycle of DED involves tear film instability, which is commonly measured through tear break-up time (TBUT). The ocular protection index (OPI) is the ratio of TBUT to the interblink interval. The interblink intervals are usually shorter than or equal to TBUT in a healthy eye. During digital screen use, increased interblink intervals and lower TBUT lead to an OPI of <1, which indicates that the tear film break-up occurred with the interblink interval (time between two blinks/when eyes are open), thus leading to an unprotected or compromised ocular surface, indicative of DED (or EDE) (9).

Tear volume

Tear meniscus volume, known to be mainly composed of aqueous tear volume, is reduced in DED patients. It is measured as tear meniscus height (TMH) through slit-lamp or anterior segment optical coherence tomography (OCT), with a cut-off value of <0.2mm for diagnosing aqueous-deficient dry eye (ADDE) (3).

Schirmer test without anesthesia

Schirmer's test also measures the tear volume. A value ≤5mm/5min is indicative of ADDE (5).

Tear homeostasis markers
 

Ocular surface staining

Fluorescein and lissamine green stains are commonly used to assess corneal and conjunctival damage (Oxford and DEWS scheme) (3). The pattern and intensity of staining are evaluated under the slit lamp, semi-quantitatively, where DED is indicated by corneal staining (> 5 fluorescein spots), conjunctival staining (> 9 lissamine green spots), or palpebral conjunctiva and lid wiper (stained zone width with the combined dyes of ≥25 percent and length ≥2 mm) (3). Although ocular surface staining is not a well-established diagnostic criterion for distinguishing ADDE and MGD, the staining across the upper and lower lid margins is likely to be observed with MGD, whereas interpalpebral or central staining is associated with ADDE (10).

Tear film break-up time (TBUT)

TBUT is defined as the interval between a complete blink and the initial first break in the tear film. It indicates tear film instability and lipid layer quality; short TBUT (<10 seconds) shows poor lipid layer quality; indicative of DED (10). Nonetheless, it is a surrogate marker and is not considered an established test that can differentiate between EDE and ADDE. A noninvasive TBUT (NIBUT) can be evaluated (without fluorescein) by assessing the reflections of patterns or rings from the tear film through videokeratography, or the appearance of lipid layer discontinuities post-blinking by interferometry. According to TFOS DEWS II, fluorescein TBUT can be considered when non-invasive procedures are unavailable (3).

Tear film break-up pattern using fluorescein

The fluorescein break-up time (FBUT) is determined post-instillation of fluorescein dye or wet fluorescein test paper placed on the lower eyelid. FBUT in the range of five to 10 seconds is indicative of DED (3).

Tear film-oriented diagnosis (TFOD) is a method proposed by the Asia Dry Eye Society, to determine and classify DED subtypes by examining the tear film breakup patterns using fluorescein. It is a simple, effective tool that can guide DED diagnosis, based on the abnormalities in each tear film layer and the ocular surface epithelium. The presence of a “line or area break-up” patterns indicate ADDE, while the appearance of a “random pattern” is associated with EDE, specifically due to MGD or increased evaporation dry eye type; whereas “spot break” or “dimple break” is due to reduced wettability of dry eye (5).

Tear osmolarity

Patients with DED have high tear osmolarity, indicating the loss of tear film homeostasis. It is commonly measured using a temperature-stabilized device, where a tear sample is collected from just above the lower tear meniscus. A tear osmolarity value of ≥308 mOsm/L or an interocular difference of >8 mOsm/L between eyes can be suggestive of DED (3).

Further evaluations for DED

Inflammatory markers. The presence of elevated levels of matrix metalloproteinases-9 (MMP-9) in the tears of patients with DED indicates inflammation and can be used as a diagnostic marker for dry eye (3). This is performed through a diagnostic test that involves collecting a 5μL sample from the palpebral conjunctiva and adding it to the test cassette; the presence of blue and pink lines (after 10 minutes) indicates a positive result (4).

Lipid layer thickness (LLT). LLT can be used for diagnosing MGD. One of the ways to measure LLT is through the LipiView II interferometer (TearScience Inc, Morrisville, NC) (4). The normal lipid layer is measured at >40 µm thickness, which becomes <40 µm when there is lipid layer deficiency or MGD (5).

Infrared thermography. A non-invasive procedure that measures ocular surface temperature through thermal imaging (using a thermography device or camera) of the ocular surface. In EDE, the average corneal cooling rate is higher compared with ADDE, suggesting considerable evaporation of the tear film.

Meibography. More advanced technology-based diagnosis for EDE (specifically MGD) includes morphologic lid features; meibum expression, and quality; and morphological assessment (in vivo) through meibography devices using noncontact infrared photography (10).

This stepwise approach to diagnosing DED, as described above, is further outlined in Table 1:

Conclusion
 

Recognizing the subtypes of DED can be complicated, due to the numerous overlapping signs and symptoms. Therefore, being able to distinguish these DED subtypes is vital to guiding DED management and treatment. Clinicians can use a combination of simple and common tests followed by specific assessments, to aid them in differentiating DED subtypes, EDE, and ADDE, for a more holistic diagnosis of the disease. The differential diagnosis of the subtypes can be further substantiated by assessments such as eyelid margin examination, TMH or tear volume, LLT, and FBUT pattern. Further, adapting the Dry Eye Wheel can be helpful for a simplified diagnostic approach in routine clinical practice.