Evidence-based understanding of dry eye disease in pharmacy: overview of the TFOS DEWS II report

Pharmacy is a frequent point of contact for patients with a range of eye conditions. Dry eye is a particularly common condition, with a reported prevalence of between 1 in 20 people and 1 in 3 people^[1]
. Patients, typically with mild-to-moderate levels of dry eye, will often present to their optometrist or community pharmacist for advice, management and treatment.

A 2016 survey of members of the Royal Pharmaceutical Society, conducted by The Pharmaceutical Journal, revealed that 57% of community pharmacists (n=227) said that they saw a patient with an eye condition at least once a day; a third said that they saw a patient with a dry eye condition at least once a day; and 80% reported that they saw a patient with a dry eye condition at least once a week^[2]
.

Many patients can be effectively managed through pharmacy without the need for referral to their GP or ophthalmologist. This article aims to provide an overview of the changes to the definitions, diagnosis and treatment of dry eye included in the 2017 report of the Tear Film and Ocular Surface Society (TFOS) International Dry Eye Workshop (DEWS)^[3]
, as well as what these changes mean for pharmacists and pharmacy teams.

Production of the TFOS DEWS report

The initial focus on dry eye disease largely began with the report of the National Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes^[4]
. This was the first formalised attempt to define and classify dry eye disease, in addition to reviewing its management, treatment, and the design of clinical trials.

In 2007, this was followed by the TFOS publication of the DEWS report, produced by 58 members from 11 countries^[5]
. Produced as a special issue of the journal Investigative Ophthalmology and Visual Science, the free report has become the ‘go to’ source of information for clinicians, researchers and industry alike.

In recognition of the exponential publication of literature since the first DEWS report, 2017 sees the publication of an updated report — TFOS DEWS II— and provides a consensus view on what dry eye is, what causes it, how it should be diagnosed and how it is best managed^[3]
. Table 1 summarises the key changes in clinical guidance included in the updated TFOS DEWS II report.

Anatomy of the tear film and its production

Before discussing dry eye in more detail and the implications of the TFOS DEWS II report, it is necessary to understand the anatomy of the tear film and more about its production^[6]
.

Despite being only around one tenth of the thickness of a human hair, the tear film is vital for maintaining healthy and comfortable eyes, in order to provide clear vision. Tears bathe, nourish and protect the eye’s surface from dryness, allergy and infection, and work to eliminate the irritants that cause discomfort and keep the surface of the eye moist^[7]
.

When the eye fails to produce sufficient tears, dry eye symptoms (dryness, burning, eye fatigue and even watering, along with transient visual disturbance [see later]) may occur and, if left untreated, can result in damage to the eye’s surface^[7]
.

The three main components of the tears are produced by glands in the orbit and the eyelid, and by cells overlying the white of the eye, in a carefully ordered structure to protect the ocular surface (see Figure 1). The tear film is often described as consisting of three layers, but it is likely these are not discrete. The lipid layer is the oily top layer of the tear film, produced mainly by the meibomian glands that are contained within the lids with openings along the lid margins. This layer helps to prevent tear evaporation and to spread the tear film over the surface of the eye. The aqueous layer is the watery middle layer of the tear film, produced by the lacrimal gland situated in the upper lateral region of each orbit. Finally, the mucin (or mucous) layer, produced by the goblet cells located in the conjunctival tissue over the white of the eye (the sclera), coats the cornea (the clear window to our vision) and holds the tear film to its surface^[6]
,[7]
.

Tears flow across the ocular surface from the eyelid glands where they are produced, spread by each blink. They are drawn along the tear meniscus (the pool of tears along the upper and lower inner lid margins), and drain through small ‘canals’ (puncta) in the nasal aspect of the eyelid into the nose.

Dry eye disease

Epidemiology

Studies suggest that between 5% and 50% of the adult population have symptoms of dry eye disease, and the condition is more common in Asian populations and in females^[1]
. It is associated with other medical conditions such as rheumatoid arthritis, diabetes and thyroid disease, as well as with anxiety and depression. Dry eye can develop after surgical procedures such as LASIK (laser), cataract or cosmetic surgery^[8]
.

Prolonged use of computers, video games, tablets and mobile phone screens can also bring on the condition. Other environmental factors that contribute to symptoms can include allergies, pollution, wind, cigarette smoke, dry environments, contact lens wear, not drinking enough water and a poor diet.

Prescription and over-the-counter medications including eye drops, allergy medication, anti-depressants and sleeping aids can also cause symptoms^[9]
.

Definition and aetiology

The consensus definition of dry eye disease from the TFOS DEWS II report is: “Dry eye is a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play aetiological roles”^[10]
.

The original TFOS DEWS workshop was the first to acknowledge that dry eye was a disease entity, with a multifactorial aetiology^[11]
. Symptoms are critical to dry eye disease diagnosis and differentiate it from subclinical ocular surface disease, although such disease may also need management, particularly in situations known to induce dry eye such as refractive surgery or low humidity environments. Visual symptoms include discomfort (typically described as dryness, burning, eye fatigue and even watering) along with transient visual disturbance (which occurs when the critical optical refracting surface of the tear film for high quality vision is disrupted). The phrase ‘loss of homeostasis’ has been introduced to convey the imbalance that is induced in the state of equilibrium of the tear film by a variety of causes. This is considered to be the unifying characteristic that describes the fundamental process in the development of dry eye disease^[7]
.

The core mechanism of dry eye is tear hyperosmolarity, which is now recognised as the key distinguishing feature of the disease. The increased solute concentration damages the ocular surface, both directly and indirectly, by initiating inflammation. Cells from the eye’s surface are damaged and lost in this process, causing tear film instability, such that the tears can no longer protect the ocular surface in the periods between blinks, and this leads to symptoms of dryness. This premature destabilisation, described as tear breakup, exacerbates and amplifies tear hyperosmolarity and completes the vicious circle of self-perpetuating events that lead to dry eye disease^[7]
.

The two main sub-classifications of the disease are aqueous-deficient dry eye (ADDE) and evaporative dry eye (EDE), with patients on a spectrum between these two types. In ADDE, tear hyperosmolarity arises from reduced lacrimal secretion, as a result of excessive drainage or more commonly, from reduced lacrimal gland tear production (see Figure 1). In EDE, excessive evaporation from the exposed tear film surface is the cause of tear film hyperosmolarity (see Figure 1)^[10]
. EDE has been reported to be four times more common than ADDE^[12]
.

Diagnosis

There are a wide range of measures that have been proposed as diagnostics for dry eye disease. These include tests of tear stability (such as the time taken for the tear film to ‘break’ on the ocular surface), tear volume (such as that measured from the tear meniscus height or from the length of paper [Schirmer] or dyed string [Phenol Red Thread test] that wets when placed in the tear meniscus over a set period of time), ocular surface damage (such as ocular surface staining from fluorescein, lissamine green and rose bengal dyes), and patient symptoms (quantified using questionnaires)^{[13]
,[14]
,[15]
,[16]
,[17]
,[18]
,[19]
,[20]
,[21]
,[22]}
. Information on how pharmacists and pharmacy teams can identify and diagnose patients with dry eye can be found in a previous learning article^[23]
.

As the disease process has become better understood, increased importance has been placed on the key features of the disease; hyperosmolarity, instability and cell damage^[24]
. The assessment of osmolarity has proved to be a key component to diagnose dry eye disease since a clinical instrument became available^{[13]
,[19]
,[22]
,[25]
,[26]
,[27]
,[28]
,[29]}
. Sensitivity and specificity of any diagnostic test depends on the ‘disease’ group criteria (severity, inclusion and exclusion criteria and instrumentation), invariably causing bias (spectrum, sampling and selection bias, respectively)^[24]
. For that reason, a level of pragmatism is needed, as well as reviewing clinical research, to determine the most appropriate test algorithm to apply.

The TFOS DEWS II report states that symptoms must be present (as required by the definition) and these should be identified by one of two well-validated questionnaires — the Ocular Surface Disease Index (OSDI, 12 questions)^[30]
or the Dry Eye Questionnaire (DEQ-5 item)^[31]
. Both of these are short, and could easily form part of a patient interaction and consultation in a pharmacy setting.

Having identified that a patient has symptoms above the threshold level (≥13 on OSDI) or ≥6 on DEQ-5), one of tear film instability (non-invasive breakup time), hyperosmolarity or ocular surface damage needs to be observed to confirm the lack of homeostasis of the tear film element described in the definition. If a diagnosis is confirmed with positive test result(s), the sub-classification of dry eye can be determined (as predominantly evaporative or predominantly aqueous deficient) by evaluating meibomian gland dysfunction^[32]
, lipid thickness/dynamics and tear volume. This further testing helps to inform the management of dry eye disease. It is rare for any of these clinical tests to be available in a pharmacy setting, and referral to a specialist optometric or ophthalmological clinic will be required for diagnostic confirmation.

Therefore, pharmacists and pharmacy teams have a role, prior to establishing the diagnosis, to ensure that more serious ocular pathologies, which might include some of the symptoms of dry eye disease, are not masked by inappropriate temporary relief of symptoms such as using artificial tears.

The key questions for pharmacists to ask as part of their differential diagnosis have been identified by the TFOS DEWS II Diagnostic Methodology Committee and are presented in Table 2^[24]
. If any of these questions identify a non-standard dry eye disease response, a semi-urgent referral to an optometrist or ophthalmologist is warranted to exclude other pathology.

Treatment

The ultimate aim of dry eye management is to restore homeostasis of the ocular surface^[34]
. While there are treatments that may be specifically indicated for one particular aspect of an individual patient’s ocular surface condition, many treatments are appropriately recommended for multiple aspects of dry eye disease.

The management of dry eye disease typically involves dealing with chronic sequelae that require ongoing management, rather than attempting to provide a short-term treatment, if dry eye issues are to be significantly reduced. The mainstay of dry eye disease management is provision of advice on modifiable risk factors (e.g. nutrition and the environment), tear enhancement (e.g. ocular lubricants), tear preservation (e.g. punctal plugs and humidity goggles), tear stimulation (e.g. secretagogues), eyelid management (e.g. lid hygiene and gland warming/massage) and pharmaceutical approaches (e.g. antibiotics and steroids). Information on how community pharmacists and pharmacy teams can best manage patients with dry eye conditions, including recommending treatments, is covered in a previous learning article^[9]
.

Pharmacists should advise patients on keeping hydrated, eating well (especially including essential fatty acid omega 3 in their diet or taking supplements, unless contraindicated), taking regular breaks from high concentration near-work tasks (e.g. using digital devices), avoiding unnecessary systemic or preserved topical medication, and minimising exposure to adverse environmental conditions (e.g. low humidity, extreme temperatures, moving air or air pollution).

If the patient is a contact lens wearer and has symptoms exacerbated or induced by the use of lenses, they should be advised to return to their optometrist or optician to try options to alleviate this issue^[35]
.

EDE can often be managed in a pharmacy setting by recommending hot compresses (commercial solutions vary in their efficacy so the effectiveness should be established before recommendation) lipid drops and liposomal sprays. If blepharitis is evident (dandruff-like scales of dead skin at the base of eyelashes), then the use of eyelid cleansers (often called lid wipes) is more effective and safer than the formerly recommended ‘baby shampoo’ management^[36]
.

ADDE is generally managed with artificial tears that increase the retention of moisture on the ocular surface between blinks. There are relatively few randomised controlled trials (RCTs) that have compared the relative superiority of a particular product to others for dry eye disease to inform between the wide range available^[37]
,[38]
.

Patients should be advised that dry eye disease management is an ongoing process and that they should return if they have not achieved sufficient relief within one and three months of trialling a new treatment.

Pharmacists are often the first port of call for many patients with dry eye disease and are important gatekeepers to the management of this chronic debilitating condition, although research shows a higher level of education and care of approach is needed^[39]
.