The accurate diagnosis of dry eye syndrome (DES), along with classification of its severity and subtype, is essential to developing an effective treatment plan. DES is diagnosed more readily today thanks to increasing awareness of the syndrome and its many irritating symptoms and also to a plethora of diagnostic screening methods. DES can significantly affect our patients’ vision and quality of life and should be detected and treated as early as possible to avoid further long-term side effects.

The initial diagnosis and management of DES involves determining the presence of the condition; only then can the presenting subtype, either aqueous-deficient dry eye (ADDE) or evaporative dry eye (EDE), be identified. These subtypes can be present individually or in combination, but unfortunately some objective tests are specific to only one subtype, such as the Schirmer test, tear turnover, and phenol red for ADDE or lid margin examination for EDE. Other tests simply are for manifestations that appear only later in the disease process, such as corneal and conjunctival staining.

corneal and conjunctival staining. In addition to determining which DES subtype is present, it is important to assess the severity to initiate an optimal treatment plan. In patients with early or mild dry eye, standard objective tests often fail to diagnose DES; however, the accuracy of diagnosis improves with increasing severity of DES.

CHARACTERISTICS

Both ADDE and EDE give rise to similar signs, and both can lead to increased evaporation and reduced tear film stability. But distinguishing between these subtypes and whether they exist individually or in combination is crucial. EDE is the most common type of dry eye, accounting for 35% to 45% of cases,^1-4 but both forms of dry eye occur simultaneously in the most severe cases.

ADDE. The cause of ADDE is a lack of aqueous tear secretion by the lacrimal glands. This can result in a concentrated tear film (hyperosmolarity) and an unstable tear film with desiccation of the ocular surface.

EDE. This dry eye subtype is most often caused by meibomian gland dysfunction (MGD), in which the lipid secretion required to control evaporation and maintain a normal tear film is abnormal. At an early stage of the disease, EDE can cause excessive evaporative tear loss with increased tear osmolarity and tear film instability, and thus present with signs similar to ADDE.⁵

In contrast to the DES seen in most patients, certain forms present with different characteristics, including those associated with autoimmune diseases. In Sjögren syndrome, for instance, autoantibodies target exocrine glands such as the lacrimal glands, affecting tear production. Sjögren syndrome can also occur secondary to systemic autoimmune diseases such as rheumatoid arthritis or lupus. Graft-versus-host disease (GVHD) is another systemic autoimmune disease that can go undetected if not screened for and treated accordingly. These autoimmune diseases, all distinguished by a severe inflammatory component during at least a set interval of the disease course, are associated with ADDE and EDE.

DIAGNOSE ACCURATELY

Our first priority as physicians is to determine if DES is present. Once the diagnosis is made, we can then determine what subtype or subtypes are present and at what severity. Symptoms often point toward one or the other form (ADDE or EDE), but symptoms alone can be inadequate for differential diagnosis of DES. The symptoms characteristic of dry eye can be experienced with a range of ocular surface conditions and tear film disorders, and they are subject to psychological overlays and influenced by alterations in sensory receptors in DES. When DES is suspected, an evaluation of the eyelids, the tear film, the ocular surface, and the lacrimal glands should be performed, as this is the best way to determine the etiology.

DES is a condition with various risk factors including age, androgen deficiency, chronic environmental stress, changes in blinking patterns, systemic autoimmune disease, the use of systemic drugs, nerve damage caused by surgery, and contact lens wear leading to instability and tear hyperosmolarity.⁵ According to the Dry Eye WorkShop, tear hyperosmolarity in ADDE is a result of reduced tear production from the lacrimal function unit with a normal evaporation rate. With EDE, in contrast, increased evaporation occurs. Increased tear osmolarity has been shown to be the principal feature causing damage to the epithelial surface and triggering a cascade of inflammatory events including an increase in inflammatory tear cytokines and apoptotic cell death. It is also responsible for initiating alterations in mucin expression, leading to ocular surface damage.⁶

PREFERRED SCREENING METHODS

Physicians have difficulty diagnosing early stages of DES because onset and progression are typically gradual. Existing tests evaluate various characteristics of the tear film, but physicians should use both experience and an adequate testing method to distinguish between the two forms of DES.

Conventional screening. For ADDE and EDE, conventional objective testing such as Schirmer test, tear break-up time (TBUT), noninvasive tear break-up time (NIBUT), and ocular surface staining produce variable results due to instability of the tear film in patients with dry eye. Tear osmolarity, on the other hand, is a global test for the presence of DES because it measures the concentration of the tear film, which is high in all forms of DES. One test of tear osmolarity is the TearLab Osmolarity System (TearLab Corp., San Diego). Although it does not differentiate between ADDE and EDE, it is an excellent measure of disease severity and response to treatment.

Tests to diagnose EDE and MGD. Tests for EDE can also diagnose MGD. These include grading lid margin disease for vascularity and lipid expression using the expression test described by Korb and colleagues.⁷ In the diagnostic expression test, pressure is applied to the outside of the eyelid similar to the amount of pressure the lid muscles exert during the blink motion (1.25g/mm²). Pressure is applied manually with a finger against any kind of suitable instrument (eg, gland expressor) placed on the conjunctival side of the lid.¹

Noninvasive tests. Another test, the LipiView interferometer (TearScience Inc., Morrisville, North Carolina), objectively quantifies lipid layer thickness by capturing images of the tear film. This noninvasive test, which uses an automated measure of a tear sample’s interferometric colors to indicate the thickness of the tear film’s lipid layer, can be used to identify lipid abnormalities, which are pathognomonic for MGD.

Patient questionnaires. Surveys can be used to quantify the frequency and severity of patients’ symptoms. For instance, the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire provides a means for patients to explain their symptoms, allowing both patient and physician to establish insight into the patient’s complaints and how these symptoms affect their quality of life.

AVAILABLE TREATMENTS

Management of DES varies from patient to patient and according to the severity of symptoms and ocular signs. Specific treatments are available to address each subtype of DES. For ADDE, artificial tear solutions lubricate the eye, stabilize the tear film, and retard evaporative tear loss. Punctal plugs and antiinflammatory and/or immune-modulating drugs are also used primarily for the treatment of ADDE. Lid scrubs and external heat are primarily used to treat EDE and MGD.

The LipiFlow System (TearScience Inc.) is another treatment for EDE. For more information, see Thermal Pulsation to Relieve Meibomian Gland Blockages.

CONCLUSION

As DES awareness increases, the development of tests to diagnose DES and improve management and treatment is crucial. However, common sense and expertise in diagnosing visible signs and understanding DES subtypes are key to controlling DES at its initial stage—before it becomes unmanageable.

Michael A. Lemp, MD, FACS, is a Clinical Professor of Ophthalmology at Georgetown and George Washington Universities, both in Washington D.C. Dr. Lemp states that he has stock in TearLab and is a consultant to TearScience. He may be reached at email: malemp@lempdc.com.

Gerd Geerling, MD, PhD, is Professor of Ophthalmology and Chair of the Department of Ophthalmology, University of Dusseldorf, Germany. Professor Geerling states that he is a shareholder of TearLab Inc., but has no financial interest with TearScience Inc. He may be reached at email: geerlingg@aol.com.

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2. Viso E,Gude F,Rodriguez-Ares MT.The association of meibomian gland dysfunction and other common ocular diseases with dry eye:A population-based study in Spain.Cornea.2011;30(1):1-6.
3. Yamaguchi M,Kutsuna M,Uno T,et al.Marx line:fluorescein staining line on the inner lid as indicator of meibomian gland function.Am J Ophthalmol.2006;141:669-675.
4. Tong L,Chaurasia SS,Mehta JS,et al.Screening for meibomian gland disease:its relation to dry eye subtypes and symptoms in a tertiary referral clinic in Singapore.Invest Ophthalmol Vis Sci.2010;51:3449-3454.
5. Bron AJ,Yokoi N,Gafney E,Tiffany JM.Predicted phenotypes of dry eye:proposed consequences of its natural history. Ocul Surf.2009;7(2):78-92.
6. [No authors listed].Methodologies to monitor and diagnose dry eye disease:report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007).Ocul Surf.2007;5(2):108-152.
7. Blackie CA,Korb DR,Knop E,Bedi R,Knop N,Holland EJ.Nonobvious obstructive meibomian gland dysfunction. Cornea.2010;29:1333-1345.

TAKE-HOME MESSAGE

• Evaluation of eyelids, tear film, ocular surface, and lacrimal glands is the best way to determine the etiology of DES.
• Once a DES diagnosis is made, the next step is to determine which subtype or subtypes are present.
• ADDE is caused by a lack of aqueous tear secretion.
• EDE is most often caused by MGD