How is dry eye syndrome diagnosed?

How is dry eye syndrome diagnosed?

Dry eye syndrome is a disease whose number of cases has been increasing in recent years due to a large number of factors that contribute to its appearance. For some years now, dry eye syndrome has been considered a public health problem 1 and corresponds to one of the most frequent reasons for consultation for visual health professionals. That is why, in the last three decades, institutions such as the Tear Film and Ocular Surface Society (TIFOS) and the Dry Eye WorkShop (DEWS) have published the results of their research. In 2007, DEWS released the first globally accepted definition of dry eye. However, in 2017, due to joint work between TFOS and DEWS II, the concept of dry eye was redefined as: “Dry eye syndrome is a multifactorial disease of the ocular surface characterized by a loss of film homeostasis. Lacrimal, accompanied by ocular symptoms, in which the instability and hyperosmolarity of the tear film, inflammation and damage of the ocular surface, and neurosensory abnormalities play etiological roles” 2.

Numerous studies have been carried out for more than a decade with dry eye syndrome, particularly it has been reported that risk factors are fundamental to understand the disease, among which the following stand out: female gender, age 3, under-correction of the defect refractive 4, refractive surgery, thyroid disease, educational level 5, autoimmune disease 6, use of video terminals 7, hormonal changes, environmental factors 8, cataract surgery 9), exposure to ionizing radiation 10, among others. Figures obtained in previous research 11), (12), (5, suggest that between 17% to 21% of the studied population has a dry eye disease. Therefore, multiple factors can trigger the disease. However, there is no protocol regarding the diagnosis and treatment of the disease, precisely due to the multifactorial causes and the diverse behavior that the clinical picture can present in similar conditions.

Therefore, the development of new technologies is crucial to lead to an assertive diagnosis and treatment since the signs and symptoms of the patient are not very specific when it comes to distinguishing between various types of the disease 12. There is currently no “Gold Standard” available to diagnose the disease 13, traditional clinical methods such as tear film rupture, Schirmer test, green lysine, among others 14 must usually be applied to correlate the results subsequently; however, these tests are subject to the collaboration of the patient and the skill of the examiner, which can result in false positives or false negatives, reducing the accuracy of the diagnosis.

Therefore, biomarkers emerge as a quantifiable and useful instrument to identify pathogenic processes, biological processes, and the effectiveness of treatments 15; therefore, they can be used to prevent, identify or measure a risk 16, as well as diagnose, understand mechanisms, evaluate the severity of a pathology 17 and monitor the disease 18; In other words, in the presence, absence or high concentration of a biomarker, a pathological state can be detected even before it begins, or it will allow recognizing the effectiveness of treatment from the first stages of its application. Consequently, a biomarker will reduce uncertainty by identifying healthy people from sick ones. 19; in this sense, it will have sensitivity and specificity to detect the disease 20.

According to the working group for the definition of Biomarkers of the National Institutes of Health (1998), they indicated that biomarkers “objectively measure and evaluate as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention.” use immunoassay techniques and biochemical methods to detect proteins secreted by the lacrimal gland or generated by inflammatory or epithelial cells of the ocular surface 21. Therefore, biomarkers are measurable proteins in biological fluids 22) such as blood, urine, and tears. Even the first studies of biological samples for the diagnosis of dry eye date back to 1990 “pre-proteomic era” where they recognized 10 tear proteins 23) among them: lactoferrin, lysozyme, secretory immunoglobulin A, Zinc alpha2 glycoprotein, albumin, immunoglobulin G, and transferrin; who presented direct involvement with dry eye syndrome23. Based on these findings, more markers were identified that could be linked to the pathophysiology of the disease 24), (25, hence, various ways have been developed to quantify and categorize the prote Ocular surface lines 26.

In this way, biomarkers are an alternative tool to diagnose dry eye syndrome, and the advantage is that it can use tear or conjunctival samples to evaluate ocular tissue; allowing the subtypes of the disease to be explained with greater precision 13, making the treatment increasingly specific to each patient 12, when evaluating the response to the treatment from its application. However, its viability has been questioned due to the difficult access, high costs 27, and the requirement of qualified personnel to take and analyze the samples for each procedure 28. However, biomarkers are alternative diagnostic methods that evaluate the ocular surface, allowing accurately detecting the presence or absence of dry eye syndrome, which could positively affect the patient’s quality of life. For this reason, the present review aims to describe the main advances in ocular surface biomarkers and recognize their clinical application for diagnosing the dry eye between 2013 and 2018.


A systematic narrative review was carried out to describe state-of-the-art, from a theoretical perspective, on the biomarkers of the ocular surface used for the diagnosis of dry eye disease. The search was carried out in the Science Direct, Pubmed, Proquest, and Scopus databases, limiting it to articles published between 2013 and 2018. The search strategy used controlled descriptors: “Dry Eye Syndrome,” “biomarkers,” “tear proteins, “Eye proteins” selected in DCS and Pubmed, in the same way, boolean operators AND, OR, and NOT were used.

The review included primary and secondary publications in Spanish and English; between the years 2013 to 2018, descriptive, semi-experimental, and experimental research designs were approved, articles with one or more of the mentioned descriptors reviewed in the title, abstract, keywords, or introduction. Studies mentioned in the body of the work methods include impression cytology, osmolarity, microscopy, and traditional methods (Schirmer I and II, fluorescein staining, Break Up Time, green lissamine staining, phenol red thread) were excluded. Literature review and meta-analysis articles were excluded.

What are the signs and symptoms of dry eye syndrome?

 Shooting, burning, or itching pain in one or both eyes
 Red or watery eyes
 Pain in the eyes when looking at the light
 The sensation of having something inside the eye
 Blurred vision or vision loss
 I am not able to cry or produce tears when sad or angry.

How is dry eye syndrome diagnosed?

Inform your doctor of your symptoms and the medications you take. Your doctor will examine your eyes under a microscope to see if they are inflamed or injured. He will also check if there are any problems with your tear glands. You may measure the moisture in your eyes with a tiny test strip.