The Dry Eye Patient

By Scot Morris, OD

The three year COPE certification for this course has expired so it can no longer be used to obtain CE credits. No representation is made that the information included in the course is still valid or correct. The course is presented for reader interest only. No examination is available for this course.

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Introduction
While the condition of dry eye arguably affects more of our patients than any other ocular disease, it remains an elusive and difficult condition to manage. Although many doctors diagnose and treat based solely on tear aqueous levels, management of dry eye conditions must also include a thorough examination of the lipid layer, ocular surface and eyelids.

Dry eye syndrome can be defined as a disorder of the tear film due to tear deficiency or excessive tear evaporation that causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort. This definition encompasses a wide variety of possible etiologies for the dry eye conditions, though all facets of the above definition need not be present for diagnosis.

This paper explores the basic pathophysiology and diagnostic testing to make the correct diagnosis regarding the specific etiology behind the various forms of ocular surface disease that affect our patients.

We will briefly review normal physiology and function as it pertains to the various forms of ocular surface disease and dry eye syndrome (DES). Our goal is to provide the basic tools to enable effective diagnosis and treatment for many of the dry eye conditions encountered, thus increasing patient comfort and preserving vision.

Getting the Facts
The first step in the assessment of any ocular disease should involve a thorough patient history. Specific attention should be paid to the patient's chief complaint as it relates to daily visual function. Common chief complaints that may be related to DES are listed in Table I.

The clinician should question patients on certain environmental issues that might predispose them to certain types of dry eye conditions. Prolonged reading or computer use, contact lens discomfort, frequent air travel or living in arid conditions may all shed light on issues related to tear evaporation.

Exposure to cigarette smoke or other environmental allergens or a history of frequent itching or discharge may elucidate certain inflammatory etiologies or an associated allergic condition.

Consideration should also be given to patients who report recent hormone changes, autoimmune disease or related symptoms, systemic allergies, and plastic surgery or ocular injury including surgery.

A complete list of medications should also be obtained with special attention paid to medications known to affect either tear film production or ocular surface health. Drugs such as oral antihistamines, anti-depressants, or those used for hormone replacement therapy have been shown to significantly decrease aqueous production.

The clinician also needs to determine the frequency and the patient's perceived effectiveness of artificial tear therapy if it has been started, as well as any other treatment options that have been attempted by either the patient or other clinicians.

By gathering as much information as possible relating to ocular comfort, visual status, and environmental or lifestyle issues, the clinician can significantly increase his or her chances of determining the correct etiology and thus being able to provide proper management for the patient's disorder.

Observations
Once a thorough history has been obtained, the clinician should begin asystematic assessment of the patient. By developing a specific pattern of observations, the clinician may not only increase the sensitivity of the exam but also the efficiency.

Table II lists a recommended assessment pattern for a potential dry eye patient. It combines a thorough observation of the ocular surface, tear film, and drainage mechanism with a time efficient flow of tests.

Ocular Surface
The ocular surface provides many clues as to the etiology and severity of dry eye syndrome. When examining the ocular surface evaluate both the corneal and bulbar conjunctival surfaces. Each may give distinct clues to the potential etiology of the ocular surface disease (OSD). The status of the ocular surface must be evaluated as a whole and for distinct entities or patterns that can elucidate the cause of dry eye. Evaluation of the ocular surface is an extensive process that covers a large surface area. The ocular surface is divided into six sectors with each sector being evaluated individually.

Suggested Sectors for Evaluation

Ocular Surface Staining Patterns
When evaluating the ocular surface, note any surface staining patterns that may be present. By assigning a score to the intensity of the staining pattern in each sector, the clinician can more effectively analyze changes over time. The individual sector scores can be added to obtain a total score.

Existing cellular damage or loss known as punctate epithelial erosions are easily seen with fluorescein and rose bengal (RB) or lissamine green (LG) vital dyes. Sodium fluorescein stains areas of cellar loss whereas rose bengal or lissamine stains devitalized or degenerated epithelial cells as well as mucous filaments. When using either type of dye, grade the surface damage on a scale from 0 to 3 in each distinct sector. Likewise be aware of specific staining patterns that may indicate certain etiologies or contributing factors to the ocular surface disease.

These factors include:

The palpebral conjunctiva should be evaluated for hyperemia, follicular involvement, punctate epithelial erosions, foreign body presence or cicatricial changes. Hyperemia can indicate an inflammatory process and can also be graded on a scale of 0 to 3 in severity.

Interpalpebral conjunctival punctate erosions are indicative of OSD secondary to changes in tear film osmolarity. Nasal loss is typically more severe than temporal loss due to a greater concentration of goblet cells in the nasal conjunctiva. This area is also more severely affected by osmolarity changes since the tear film pools in the nasal canthus. One clinical pearl to keep in mind is that nasal conjunctival staining often presents much earlier than corneal staining.

Tear Film Stability
Arguably the most indicative test of the tear film and the ocular surface overall status is tear film stability. Overall tear film stability can be affected by many ocular surface conditions including mucin contamination, epithelial changes, and many additional factors that will be discussed in other sections of this article.

Mucin contamination occurs when hydrophobic lipid diffuses from the superficial layer and overwhelms the hydrophilic mucin causing tear film rupture. Epithelial changes can also reduce tear thickness, by either failing to secrete a proper glycocalyx or because mucin in brought into closer contact with the lipid layer, which induces tear rupture. For this reason it is important to always assess negative staining patterns as well as positive staining patterns. Also look for negative staining patterns and consistent tear film instability that may be an indication of surface mucin or glycocalyx abnormalities.

Tear film instability

Aqueous Layer
When evaluating the aqueous layers, the clinician must keep in mind that various etiologies can result in abnormalities. Whether it is lacrimal gland disease, delivery issues, or changes that occur at the ocular surface, the pieces of the puzzle must be organized to accurately arrive at a correct diagnosis.

Lacrimal gland disease can be the result of primary or secondary Sjogren's syndrome, but it is often associated with an etiology that is not related to clinically significant Sjogren's. Whether the etiology is secondary to changes in the neurosecretory reflex arc or changes in immunomodulation of the lacrimal gland, the net result is a decrease in secretion of the aqueous component.

Remember that the ocular surface and the lacrimal gland function as a unit via a neuronal feedback loop. Reduced flow of the lacrimal gland because of any of the causes mentioned results in an abnormal ocular surface, reduced sensation, and a disruption of this loop. Diminution of the neural tear stimulus can occur because sensory nerves adapt to prolonged ocular surface irritation thus decreasing the stimulus for reflex tearing. In essence, this downward spiral leads to progressive ocular surface desiccation and disease. Fifth nerve disease and refractive surgery patients can also have an insufficient-type dry eye due to an altered feedback loop. Contact lens wearers also suffer from sensory adaptation. This decreased sensitivity can result in decreased lacrimal secretion.

A patient with exclusively aqueous deficiency typically complains of dry, burning eyes starting approximately 30 minutes after waking and symptoms progress in severity throughout the day. Symptoms are often exacerbated by a dry environment or in large open spaces with conditioned air such as malls or airports.

When evaluating the tear prism, the clinician needs to be alert for changes in tear film viscosity as well as in tear volume. Tear volume can be measured either by subjective means or quantitatively with Schirmer strips or a phenol red thread test.

Subjective Tear Measurements
Clinical observation can provide a general overview of the ocular surface and tear prism. Evaluate the height of the prism at the lower lid margin and over the surface of the cornea and conjunctiva. The normal tear meniscus height is between 0.2 and 0.5 mm. If there is minimal loss, there can be a small decrease in the nasal part of the tear prism due to concurrent drainage through the puncta.

A generalized decrease in tear volume will be represented as an absent or very thin line of fluorescein. Again, this provides a general overview but should not be used as a predictive observation.

Normal tear prism layer stained with NaFl

Thin tear prism layer stained with NaFl

Schirmer Tests
For many years, this test has been the gold standard for determining tear volume. Some advances have been made and there is now a calibrated Schirmer available with a color bar. The Schirmer test is based upon mechanical reflex stimulation of the tear production and is actually a test of reflex tear production when performed without anesthesia.

There are many factors that affect the results so the procedure must be conducted carefully. Place a dry Schirmer strip over the middle to lateral 1/3 of the lower eyelid. The patient is then instructed to look forward and blink normally. The strip is removed after 5 minutes and amount of wetting is recorded in millimeters.

Schirmer's with anesthesia tests basal tearing and has a normal value of 12 mm at 5 minutes. Schirmer's without anesthesia tests basal and reflex tearing and has a normal value of 20 mm at 5 minutes. Some clinicians prefer the non-anesthetized test because anesthesia disrupts the normal secretion process by eliminating the feedback stimulus and changing the tear film surface tension. Various studies have found that proparacaine can reduce mean test values by 40%.

Despite their relative ease of use, both types of Schirmer test have poor sensitivity and specificity.

Phenol Red Thread
The phenol red string test (Zone Quick - Menicon) is a sterile cotton thread that is draped over the non-anesthetized lid margin. It changes color upon aqueous contact and the length of colored thread is measured.

This test is used to evaluate the tear secretion quantity without inducing significant reflex tearing. It is probably a better test of aqueous production than the Schirmer test because it doesn't stimulate reflex tearing and is performed over a shorter time period. The normative value is 13±4 mm of wetting over a fifteen second period.

Tear Film Stability
Tear film instability is also very helpful in investigating tear production. Evaluation of tear instability can be done by either invasive or non-invasive methods.

Tear film rupture results in exposure of the aqueous to the environment, evaporation, and subsequent increase in tear film osmolarity. The predominant thought is that the condition of the lipid layer regulates tear rupture and subsequent evaporation. However, tear film rupture can also be caused by contamination of the mucin layer by meibum, local desiccation, or drainage through the damaged epithelium. The most specific tests for detecting these disorders are the tear breakup time (TBUT) test and the tear-thinning test (TTT), which measures tear film stability.

Invasive Tear Break Up Testing (TBUT)
A fluorescein strip is wet with 2-3 drops of non-preserved saline and touched to the inferior temporal palpebral conjunctiva. The patient is instructed to blink a few times then open the eyes. Using a broad slit lamp beam with a cobalt blue filter, the time from the last blink until the first dry spot occurs is recorded. A reference value of 20 to 30 seconds averaged over 3 measurements is considered a normal value,10 to 15 seconds is considered borderline, and less than 10 is abnormal. When evaluating the TBUT, all areas of the cornea must be observed. Unfortunately, results of this test are not very reproducible and highly dependent on multiple factors that are difficult to control.

Non-invasive (NITBUT)
The reflected mire of a keratometer or topography machine, or a simple grid can be projected onto the ocular surface to evaluate the tear film. The patient is instructed to blink normally then the time until the mire or grid diffuses is measured. The normal value averaged for three consecutive measurements is greater than 10 to 18 seconds. Results of this test are dependent upon keratometer illumination, corneal area viewed, and palpebral aperture size.

Once the aqueous has become part of the precorneal tear film, it can undergo changes affecting its constitution and tonicity. The tonicity of the tear film is a dynamic relationship that is affected by the rate of evaporation, tear secretion, tear volume, and drainage rate.

Various studies have shown normal tear fluid leaving the lacrimal gland is isotonic suggesting that the tears become hypertonic on the eye secondary to evaporation of the aqueous component. This hypertonicity causes subsequent damage and loss of the conjunctiva and corneal epithelium.

Tear osmolarity will be increased by any disorder that increases tear evaporation or decreases tear secretion. This includes meibomian gland dysfunction and lacrimal gland disease. Osmolarity increases often lead to a decrease in goblet cell density and corneal glycogen levels, which in turn lead to epithelial defects and poor wetability of the ocular surface. As mentioned earlier, this is especially related to interpalpebral nasal bulbar conjunctival staining patterns.

Lipid Layer
Lipid disorders are the most under-diagnosed and probably the most important contributing factor in many dry eye cases. The symptoms of meibomian gland dysfunction (MGD) often vary depending on the presentation. Patients with MGD report that their eyelids are stuck together in the morning, foreign body sensation, swollen tender lids, and blurred vision after prolonged near tasks that improves immediately following a blink.

They may also report excessive tearing, contact lens intolerance, allergic symptoms, or chronic eye rubbing. A defective lipid layer is proposed by many to be the primary cause of aqueous component evaporation, changes in the tear prism, and subsequent osmolarity imbalance.

MGD commonly results from congestive/obstructive meibomianitis secondary to changes in secretion constitution, volume, and deposition. It doesn't necessarily imply inflammation but is often associated with other lid changes that affect the glands, ducts, or orifices. A thorough history and examination of the gland, ductules, and orifices will give clues as to the possible etiology of many conditions.

Careful observation of the meibomian glands and the resultant lipid layer can give many clues to the etiology of certain ocular surface conditions and their relationship to dry eye signs and symptoms. Meibomian glands should be evaluated according to position, visible number, size and length, presence of obstruction, and orifice condition.

Meibomian gland obstruction

By trans-illuminating the everted gland, the size, number, and length can easily be determined. The normal acini are seen as fine striations of the yellow glands and gray fibroelastic intercellular tissue. Congestion of the glands will cause enlargement and be visible as a yellowish globular line.

Observation of meibomian gland obstruction or congestion, or even loss or atrophy of the glands can suggest various forms of meibomian gland disease. Absence or dropout can be determined by the absence of the intermittent striations or small isolated acini with no connection to the ductules.

The meibomian glands should also be evaluated to determine the volume of lipid in reserve, the pressure needed to express fluid, and the quality of meibum expressed. Examination of normal patients and the lipid volume of those patients can provide a good reference level. By comparing the volume expressed with the gland appearance, the etiology behind the condition is usually evident. The pressure needed to express the gland can also aid in determining the presence of stenosis or normal flow pattern for the patient. The turbidity or clarity of the meibum also gives evidence of the condition. A summary of this grading system is provided in Table 3.

Table 3 - Grading System

Lids
The lids are often overlooked but crucially important to tear film function. Aside from their protective properties, they provide tear film stability and proper lipid deposition. They also assist in effective removal of the tear film and cellular waste products.

Lid abnormalities include problems with normal apposition, lagophthalmos, incomplete blink, and inflammation of the lid margins.

Mechanical, cicatricial, senile, or inflammatory changes are common causes of poor lid apposition. The normal lid should snap back into position when lightly retracted. Absence of this action can represent early loss of elasticity and result in poor lacrimal drainage, stagnation of the tear pool, changes in surface tension of the tear film, increased evaporation, an altered concentration of tear proteins, and an increased risk for various types of conjunctivitis.

It is equally crucial to evaluate lid closure for lagophthalmos and incomplete blink patterns. Either of these can lead to increased evaporation, altered concentration of tear solutes, desiccation, and focal loss of the surface epithelium.

Incomplete blink patterns can be diagnosed by observing the normal blink fluorescein distribution patterns in the tears. Patients with lagophthalmos often complain of a gritty or foreign body sensation or that their eyelids stick together upon waking without the presence of discharge. Lagophthalmos can be observed by having the patient gently close the eyes for about two minutes while the practitioner look for cracks, slits or fasciculations with a slit lamp or trans-illuminator. Lagophthalmos will result in inferior punctate epitheliopathy early in the day whereas incomplete blink patterns will cause inferior band staining that present later in the day.

Lagophthalmos

Other lid related disorders, such as blepharitis, might also contribute to various forms of ocular surface disease. Clinically, anterior blepharitis patients present with dry eye symptoms, injection, hyperemia and chemosis of the ocular surfaces, and inflamed lid margins with possible focal epidermal ulceration. The bacteria and their byproducts can also form collarettes around the bases of the lashes.

Bacteria can also invade the meibomian glands leading to obstructive primary meibomianitis. Seborrheic blepharitis is another commonly under-diagnosed type of blepharitis. Seborrheic blepharitis presents with oily scales around the lid margin and associated seborrheic dermatitis elsewhere on the patient's face or scalp. The excessive production of abnormal sebum and its invasion of the mucosa often leads to chronic lid margin inflammation and contamination of the tear layer.

The excessive oil can also provide a suitable substrate for bacterial growth and lead to a mixed blepharitis. Oily scruffs around the base of the lashes, chronic inflammation of the lid margins, and underlying meibomianitis are the characteristic clinical features associated with posterior blepharitis. Since there is a wide range of lid disorders, patients may present with a wide variety of symptoms including epiphora, foreign body sensation, photophobia, redness, discharge, swollen lid margins, and occasional itching.

Outflow Mechanism
Correct lid apposition is also crucial in correct functioning of the outflow mechanism. Punctal apposition needs to be assessed as well as punctal patency for the presence of any inflammatory conditions that may affect the outflow mechanism.

Outflow testing can include tear film index as well as one of the various types of Jones' test. The best overall test for drainage disorders is a tear clearance test. It is best to evaluate both the tear clearance and tear production to determine the true etiology of the patient's dry eye problem.

Tear Clearance Test
To perform this test, fluorescein from a paper wetted with saline is instilled into lower fornices. (Anesthesia is avoided because it will increase the evaporation rate. Fluress will also increase surface tension as well as the surface volume.) Wait 5 minutes then place a Schirmer strip into the fornices for 5 minutes. Evaluate the length of wetting against a standardized grading system.

Grading system

The Tear Clearance Rate (TCR) is determined by a grading system based on the intensity of staining on the strip and standardized as 1, 1/8, 1/16, 1/32, 1/64, 1/128, 1/256.

The Tear Function Index (TFI) is determined by the value of the Schirmer/TCR. It actually measures both tear secretion and drainage. Values below 96 are consistent with dry eye and values below 34 are consistent with a Sjogren's diagnosis.

In general, the higher the TFI the better the ocular surface condition. A low Schirmer with high TCR suggests an outflow system that is working too well for that person's specific aqueous production. A high to normal tear production with slow clearance and epiphora symptoms suggests an obstruction of the outflow system.

Evaluation of the remaining drainage system is more difficult. It incorporates use of the Jones I and II tests. The Jones I test involves placing fluorescein dye in the tears, waiting 5 minutes, and then having the patient blow their nose. The nasal discharge is examined under ultraviolet light for the presence of fluorescein, which would indicate patency. This test is not specific for patency of the upper or lower punctum on the same side nor can both eyes be tested at the same time. It is specifically designed to indicate patency of the nasolacrimal duct.

Putting It All Together
As is apparent, ocular surface disease, specifically dry eye syndrome, is a complex condition. It requires astute observation, knowledge about various disease etiologies, and a thorough ocular and systemic history.

It is crucial to diagnose the correct disease mechanism prior to considering management of any kind. In many situations there may be multiple causes and only careful assessment over multiple visits will lead to the correct diagnosis and proper treatment plan.

A Quick Note on Treatment
Though the treatment of DES and related ocular disease is an extensive and growing subject, a few rules hold true. Most patients have more than one condition contributing to their dry eye complaint and the causes of their condition must be carefully assessed.

Therapeutic goals in DES management include controlling or eliminating the symptoms, maintaining and preserving visual acuity, and preventing complications secondary to desiccation and inflammation. Dry eyes need to be treated on a daily basis with a fairly strict regimen. Many conditions do not have treatments that provide immediate results.

Sometimes it has taken many months or years for the patient to develop most of their signs and symptoms. It is normal to take a few months to significantly improve dry eye problems.

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