Comparison of Schirmer test values between patients with aqueous deficient dry eye and healthy participants

Dry eye disease (DED) was redefined by the Tear Film and Ocular Surface Society (TFOS) at the Dry Eye Workshop II (DEWS II) as a multifactorial disease of the ocular surface characterized by loss of tear film homeostasis accompanied by ocular symptoms [1, 2]. The TFOS DEWS II classified DED into two main types: aqueous-deficient dry eye (ADDE) and evaporative dry eye (EDE; [2]). The tear aqueous component is important for ocular surface health and its loss of homeostasis may be at the same time a key pathogenic mechanism and a diagnostic sign in the ADDE subtype [3].

Secreted tears are distributed over the ocular surface during the blinking process, departing via evaporation and drainage. Tear volume and production are key components of tear dynamics since they are directly related to the final total aqueous component [3‐7]; a decreased tear volume on those variables is assumed to be a diagnostic indicator of ADDE. The Schirmer test, phenol red test, and the tear meniscus height (TMH) have been used as diagnostics tools for identifying individuals with ADDE [8‐10]. The Schirmer test is an easy-to-use method; nevertheless, its 5‑min duration is a disadvantage for most clinicians, generating discomfort due to the invasiveness of the strip compared to other tests [11, 12]. Simplifying clinical procedures by reducing the performance time may have benefits for practitioners and patients alike.

On the other hand, tear film parameters usually remain stable over time and between eyes in healthy individuals. However, in ocular surface diseases such as DED, disruptions to tear film homeostasis lead to increasing changes in the diagnostic values over time or between eyes [13]. This variability offers valuable insights into the clinical settings. Lower disparities may indicate temporary effects within compensatory mechanisms [14, 15]. Studying inter-eye variations is becoming a significant field in scientific research, potentially streamlining diagnostic processes and reducing associated costs. While prior research has explored inter-eye differences in primary diagnostic indicators such as osmolarity, the potential of the Schirmer test for the diagnosis of DED or even for the detection of its subtype has not been investigated to date [1, 14‐19].

The present study aimed to (a) analyze and compare the values of the Schirmer test over time and between eyes of healthy volunteers and individuals with ADDE as well as to (b) calculate the diagnostic cut-off criteria of both study parameters for each time point.

In accordance with the recommendations of the TFOS DEWS II Diagnostic Methodology subcommittee, first a series of tests were conducted to differentiate between participants with DED and healthy individuals: assessment of DED symptoms, fluorescein tear film break-up time (FBUT), and corneal and conjunctival staining [1, 2, 20]. The diagnostic thresholds used to identify DED were Ocular Surface Disease Index (OSDI) ≥13, FBUT <10 s, and corneal staining (Oxford grade) > 1 [1, 2, 20]. Additionally, TMH was measured to rule in or to rule out the presence of ADDE, with a diagnostic cut-off set at TMH ≥0.20 mm [2, 20, 21]. Participants were included and classified as having ADDE if they failed to fulfil all the inclusion criteria in both eyes and were assigned to the healthy group if they passed the cut-off inclusion criteria in all the tests in both eyes.

Once volunteers were recruited and grouped based on the inclusion criteria, qualified participants were scheduled for a single session where the Schirmer test was performed. Throughout the study, laboratory conditions of temperature, light, and humidity were kept constant (temperature 20–23 °C, humidity 50–60%).

The main disadvantage of the Schirmer test, a 5-min examination, is its prolonged duration; it is common for individuals to express an unpleasant experience caused by the discomfort generated by the strip during the procedure. Consequently, some clinical research is needed to seek the possibility of minimizing the duration of the test, as well as the need to perform the test in both eyes of each participant. The present study aimed to analyze and compare the values of the Schirmer test over time and between the eyes of healthy volunteers and participants with ADDE.

According to the DEWS II classification report, there are two main DED types: ADDE and evaporative dry eye [2]. It is important to differentiate between the two DED types due to the subsequent management that will be different for each. While the EDE subtype is usually related to lipid layer alterations (therefore, diagnosed based on meibomian gland malfunctions), the ADDE subtype is related to the aqueous phase of the tear (discriminated based on a test that evaluates total tear volume). Tears are secreted and subsequently distributed over the ocular surface during the process of blinking, departing from the ocular surface via evaporation and drainage. Tear meniscus evaluation offers a noninvasive indication of the total volume since it is related to the total tear volume [4‐7]. It has been estimated that the tear meniscus holds 75–90% of the total tear volume [4]; therefore, the evaluation of its characteristics has been revealed as a useful tool [38‐42]. The TMH has been proposed in the DED diagnostic test battery of the DEWS II as a criterion to detect the presence and estimate the severity of the ADDE subtype [20]. One strength of the present study is the use of strict criteria to differentiate between healthy volunteers and patients with DED based on the diagnostic test battery of the DEWS II (higher symptomatology, lower stability, and damage presence) and to ensure focus on individuals with ADDE (lower tear volume).

There was a statistically significant difference in the Schirmer values between all time points of the test in both groups. When the results were compared between groups point by point, a difference was found even from the first time point. These results may suggest that the 5‑min test could be shortened by establishing adequate cut-off criteria to discriminate ADDE individuals; previous authors made a similar suggestion [12, 43]. In the present study, these criteria were calculated and reported.

It is important to note that in the first minute of the test, the wetting of the filter strip was conducted at an accelerated rate, but in the next 4 min, it seemed to decrease significantly (Table 2). Previous reports have hypothesized that this phenomenon may occur because of the presence of a series of processes [9‐12, 44]. First, there is a natural initial accumulation of tears in the fornix previous to the strip insertion; this is probably why the wetting of the filter strip occurred at an accelerated rate for the first minute and then slowed down afterward [9, 10, 12]. Second, the sensory receptor adaptation input of the central nervous system becomes reduced over time to prevent sensory overload and therefore the sensation is perceived as less intense; this may mean that the rapid wetting of the first minute could occur mainly by reflex tearing [12, 44]. Third, the evaporation of the aqueous phase from the strips increases over time, since a higher wetting surface allows for a physically higher evaporation rate; there is another inner influence on this variable, for instance, comparisons between different testing sites or between different regions of the world could be affected by environmental differences [9, 12]. And finally, it has been hypothesized that there is a negative hydrostatic pressure within the tear meniscus over the wetting part of the filter paper strip that slows the wetting process over time because of this pressure [11, 12]. The fact that no differences were found in the present analyses between healthy volunteers and participants with ADDE regarding the first time point of the test could be a significant limitation to reducing the clinical performance time of the test to only 1 min. However, the present study also emphasizes that the specific cut-off values identified during later time points offer a more reliable and practical approach for diagnosing ADDE. It indicates that accurate differentiation between patients with ADDE and healthy participants can be achieved as early as the second minute of the Schirmer test. Using this early time point, the test duration can be shortened without compromising the diagnostic accuracy, providing a more comfortable and efficient method for distinguishing patients with ADDE from healthy individuals.

In the second part of the analyses, it was found that there is no variation in the absolute Schirmer inter-eye difference between time points, neither in patients with ADDE nor in healthy participants; besides, there is no difference in this value during the first, the fourth, or the final time point between both groups. In this sense, previous reports also found no significant difference in test scores between eyes in the Schirmer test [12] and in other DED diagnostics tests [16, 17]. The variability or increasing variation in parameters is a statistical characteristic of the cause of heteroscedasticity in DED patients. The heteroscedasticity is considered a clinical indication of the loss of tear film homeostasis that occurs with dry eye [16, 18, 45]; indeed, inter-eye variability is a hallmark and a clinical target of DED. It has been suggested that the higher value of the two eyes obtained on a test should be used in clinical practice during dry eye management, while the lower value seems to reflect the transient effects of compensatory mechanisms [1, 14, 15, 18]. The present study results open the door to the possibility of reducing the test to only one eye when both eyes show a similar severity status, especially if the test is performed for its full 5‑min period. It is proposed in the literature that the Schirmer test measures the reflex tearing in response to irritation of the conjunctival surface by the inserted Schirmer strip [11]; this may be the origin of the individual’s discomfort. Performing the test with only one eye, as well as establishing a shorter period for the test, may reduce the unpleasant experience for the participants and improve the time spent in a clinic session. These cut-off values may also support the option of conducting the Schirmer test on only one eye under specific conditions, especially when both eyes show similar severity. The present study found no significant differences between the eyes during the test, which suggests that performing the Schirmer test on just one eye may be a valid approach in certain cases. However, this should only be considered when it is clear that both eyes exhibit similar severity, as determined by the inclusion criteria and diagnostic classification used in the present study, which required both eyes to meet specific conditions. This approach cannot be verified in other patient populations. While this adjustment could reduce discomfort for the patient, streamline the testing process, and save valuable clinical time, it is important to note that this remains a proposal that requires further investigation. This approach offers a useful starting point for future research aimed at optimizing testing protocols without compromising diagnostic accuracy. By shortening the test duration and focusing on one eye, clinicians can improve the overall patient experience while still effectively diagnosing ADDE.

It is important to note that the Schirmer test itself has some limitations. On the traditional Schirmer test, the reflex tearing occurs throughout the strip, therefore the reflex tear is not reflective of the basal tear produced by individuals in their everyday life [46]. In addition, participants are requested to refrain from blinking for as long as possible during the tests; when the eyes are open, tear evaporates to the environment and, therefore, the Schirmer wetted length is influenced by both the lack of production and the evaporation rate, which is one of the limitations of the traditional Schirmer test when trying to study ADDE. Although in the present study, patients with ADDE were selected under specific criteria for the dry eye cohort, every individual has a different evaporation rate, and therefore this may confound results. In future studies, a similar study design but with the eyes closed could eliminate the evaporation of the tear on the ocular surface.

In summary, the present study provides a complete report of the progression of Schirmer test values over time and between eyes of healthy volunteers and patients with ADDE; it also established the cut-off criteria for the different time points for both Schirmer and Schirmer |OD-OS| values. The findings suggest that reducing the Schirmer test to 2 min and performing it on only one eye when both eyes exhibit similar severity could be a practical approach in the population studied. However, given the limited sample size, these findings should be considered to be preliminary. Future research with larger samples is necessary to validate the reported cut-off values and establish robust diagnostic criteria applicable across different populations and time points. Sample size is too small to draw this general conclusion, and the authors encourage reserachers to conduct a study with a larger sample.