Aqueous-Deficient Dry Eye Disease: Evaluation and Management

Dry eye severity level





Discomfort, severity, and frequency

Mild/episodic/environmental stress

Moderate/episodic or chronic/environmental stress or no stress

Severe/frequent or constant without stress

Severe and disabling, constant

Visual symptoms

None or episodic mild fatigue

Annoying and/or activity-limiting episodic

Annoying, chronic, and/or constant limiting activity

Constant and/or possibly disabling

Lid/meibomian glands

MGD variably present


Trichiasis, keratinization, symblepharon






Corneal staining (NEI Scale 0–15)

None to mild



Severe punctate erosions

Conjunctival staining (NEI Scale 0–18)

None to mild


Moderate to marked


Schirmer test (no anesthesia) (mm/5 min)





Recommended management

1. Patient education




2. Diet modification

1. Anti-inflammatories

1. Autologous serum

1. Systemic anti-inflammatory agents

3. Lid therapy

2. Bandage or large-diameter rigid contact lenses

4. Artificial tear/gel supplements

2. Tetracycline

3. Punctal plugs

2. Surgical intervention

5. Environmental control

4. Moisture chamber spectacles

3. Permanent punctal occlusion

aModified with permission from 2007 DEWS report [38]

What Additional Questions Do You Want to Ask This Patient to Further Understand the Possible Etiology of Her Complaints?

The patient’s initial complaints are very suggestive of dry eye disease . The symptoms of dry eye disease vary among patients, but may include tearing, burning, the sensation of dryness, sensitivity to light, transiently blurred vision, and foreign body or gritty sensations. Exacerbation with activities like reading or watching TV that cause reduction in blink frequency or by environmental factors such as heating, air conditioning, and wind can be suggestive of dry eye disease. Symptoms are often worse toward the end of the day, with the exception being nocturnal lagophthalmos in which case morning is usually worse. The initial evaluation for a patient with these symptoms may be difficult as symptoms may be heterogeneous or vague. A full and comprehensive history should be taken, including identification of potential exacerbating factors, such as medications or environments, and patient behaviors, as discussed below.

Questions about the patient’s work environment should be conducted, as well as inquiring about activities that require visual concentration, such as reading or working on a computer. Computer use is associated with a decrease blink frequency through suppression of blinking, causing prolonged exposure of the ocular surface and disruption of the tear film [1]. Identifying the number of hours the patient may read or look at a computer monitor is useful for recognizing exposure as a risk factor and for elucidating potential behavioral modifications that may benefit the patient. Additional environmental factors such as direct exposure to ventilation can worsen symptoms, and desiccating environments involving heat or air conditioning may precipitate or worsen dry eye disease.

Other risk factors may include female gender and old age. Postmenopausal patients presenting with dry eye symptoms should be queried about possible hormonal replacement therapy, as replacement with either estrogen or estrogen and progestin has been shown to increase the risk for developing dry eye [2].

Any medications that the patient takes should be carefully evaluated. Ocular medications, especially glaucoma medications containing the preservative benzalkonium chloride [3, 4] have been shown to precipitate dry eye disease by causing tear film instability, loss of goblet cells, conjunctival squamous apoptosis, and disruption of the corneal epithelial barrier [5]. Systemic medications such as antihistamines, systemic retinoids, antidepressants or antianxiety medications with anticholinergic side effects, as well as diuretics may cause or contribute to a patient’s symptoms. Asking a patient if they have recently started any new medications and determining temporal relation in regard to their symptoms may be useful in identifying problem medications that should be discontinued or substituted.

While allergic conjunctivitis is not typically a component of dry eye disease, symptoms of the two entities may overlap. It is therefore important to inquire about environmental allergens and a history of seasonal allergies. It is also useful to elicit the presence of symptoms of allergic conjunctivitis, such as itching and eye rubbing. Avoidance of allergens or other irritants may be a useful intervention for relieving symptoms that may be attributable to those causes.

Contact lens wear should be assessed, as use can be a significant contributor to for dry eye disease. The patient should also be asked about any prior history of refractive surgery. Postoperative corneal hypoesthesia caused by the resection of corneal nerves during surgery can lead to dry eye through a decrease in reflex tear secretion. Usually, corneal nerves will regenerate postoperatively but may leave the patient with dry eye symptoms for multiple months before healing occurs [6].

For any patient presenting with symptoms of dry eye disease, it is important to rule out systemic causes as the underlying etiology (Fig. 1.1). Any history of chemotherapy or radiation should be elicited as these treatment modalities can damage the lacrimal and meibomian glands and cause hypofunction, leading to aqueous-deficient dry eye disease (AD-DED) as well as evaporative dry eye. A thorough review of systems should be conducted with the following disease processes in mind, as they can cause ocular surface dryness: diabetes, rheumatoid arthritis, hepatitis C, HIV, sarcoidosis, thyroid disease, lupus, Sjogren’s syndrome (SS), graft-versus-host disease, and cicatricial pemphigoid. It is prudent to question about fatigue, joint problems, dry mouth, vaginal dryness, skin lesions or rashes, shortness of breath, hearing loss, urinary difficulties, headaches, fever, peripheral edema, and peripheral neuropathy to work up these systemic conditions, as treatment will need to address the underlying condition. History of snoring and daytime sleepiness should likewise raise the suspicion for sleep apnea (often in patient with lax eyelids). The ophthalmologist may very well be the first provider to diagnose a systemic condition associated with dry eye. SS is a particularly important consideration in the initial assessment of a patient as prevalence of primary SS may be as high as 10–11% in patients presenting with clinically significant AD-DED [7]. Questions about family history of autoimmune diseases can also provide further clues. Positive review of systems concerning for systemic illness necessitates further investigation and/or referral.


Fig. 1.1
Etiopathogenic classification of dry eye disease

The patient works as a secretary at an elementary school and uses her computer frequently throughout the day. Additionally, she sits close to a heating vent. She often uses over-the-counter Benadryl to help her sleep. She does not wear contact lenses and denies any other medications. She denies any arthritis, rashes, dry mouth, vaginal dryness, peripheral neuropathy, or fatigue. Family history is negative for any autoimmune diseases. She smokes half a pack of cigarettes per day.

What Should You Look for on Physical Exam to Aid in Diagnosis of the Patient?

As typical of any patient, best corrected visual acuity (BCVA) should be assessed. BCVA may be diminished or may transiently fluctuate in patients with dry eye as due to tear film instability [8]. The tear film contributes to the refractive power of the cornea, and disruptions may produce higher-order aberrations that interfere with visual acuity. Dry eye patients often complain of a reduction in visual acuity with driving, reading a computer, and maintaining gaze as the ocular surface may dry out from suppression of the blink reflex. Assessment of functional visual acuity (FVA) , or the measure of visual acuity during sustained eye opening without blinking, may therefore be a good tool for assessment of dry eye patients [9]. FVA has been shown to be diminished in both SS and non-SS dry eye disease [10].

An external examination of the patient should be conducted to evaluate for any evidence of rosacea, enlarged lacrimal glands, or Bell’s palsy. Eyelids and lid margins should be investigated as for evidence of blepharitis, meibomian gland dysfunction, infrequent or incomplete blink, and lagophthalmos as these conditions may be addressed individually. Careful evaluation of the conjunctiva should also be conducted, and chemosis, chalasis, injection, scarring, forniceal foreshortening, subepithelial scarring, and the presence of papillae or follicles should be noted. Lid eversion should be performed. Meticulous examination may demonstrate other causes of the patient’s symptoms unrelated to dry eye disease.

The tear film should be evaluated, including the size of the tear meniscus and the tear breakup time (TBUT) . TBUT is conducted by instilling a small amount of fluorescein in the inferior cul-de-sac, followed by evaluating the stability of the tear film after the patient blinks. Blinking distributes the tear film across the ocular surface, and a broad beam of cobalt blue light at the slit lamp can be used to assess the time it takes from the last blink until the first dark patch appears, which represents tear film dissolution. Patients with AD-DED have significantly faster tear breakup times, with times of less than 10 s considered to be abnormal.

Ocular surface staining is another important tool used to assess dry eye severity. Staining can be used to identify abnormalities of the corneal surface and of the bulbar conjunctiva. Punctate staining of the inferior cornea and inferior bulbar conjunctiva are the most typical pattern seen in dry eye. Multiple stains can be used. Fluorescein is the most common and will stain areas of the conjunctiva and cornea where tight junctions have been disrupted, though corneal staining will be much more prominent. Peak staining occurs approximately 2 min after instillation. If conjunctivalization of the cornea has occurred, however, fluorescein staining will have limited utility.

Lissamine green and rose bengal dyes can be used to stain devitalized cells and allow for more prominent staining of the bulbar conjunctiva. These dyes may pick up more subtle changes and are useful for detecting milder forms of dry eye disease. Inferior staining may suggest MGD or exposure, while superior staining suggests superior limbic keratoconjunctivitis. Lissamine green possesses advantages over rose bengal as it is less toxic to the ocular surface [11].

On examination, visual acuity is 20/25 in both eyes with correction. Pupils are equal, round, and reactive without afferent pupillary defect bilaterally. Intraocular pressure (IOP) is 15 mm Hg on the right and 16 mm Hg on the left. Her lids and lashes appear normal with no evidence of meibomian gland dysfunction, lagophthalmos, or other findings. Her conjunctivas are normal. The patient’s tear meniscus appears reduced, and her tear breakup time is 10 s. Corneal staining with fluorescein reveals no punctate epithelial erosions, while lissamine green reveals minimal punctate staining of the bulbar conjunctiva in the exposure zone bilaterally.

What Additional Ancillary Testing Would Be Appropriate?

The Schirmer test is the classic test for diagnosis of decreased lacrimal secretion of the aqueous portion of the tear film. The Schirmer test is performed by placing a strip of paper in the inferior cul-de-sac and allowing the strip be wetted by produced tears over a period of 5 min. A positive Schirmer test is <5 mm of wetting with anesthetic and <10 mm without anesthestic [12], as anesthetic will reduce reflex tear secretion. Performing the Schirmer test with anesthetic has been shown to have more variable results than without [13]. The relatively low cutoff of the Schirmer test produces greater specificity at the cost of decreased sensitivity. The results of the Schirmer test may be variable between visits and should not be used as the sole criterion for diagnosis of AD-DED. However, serially abnormal results over time are highly suggestive.

Considering the importance of tear hyperosmolarity in the pathogenesis of dry eye disease, directly measuring tear osmolarity has been implemented in clinical practices since FDA approval of the osmolarity measuring device (TearLab, San Diego, CA) in 2009. It has reported to be another test to consider as part of an overall diagnostic picture [14]. Elevated tear osmolarity is suggestive of dry eye disease, and hyperosmolar tears stress the ocular surface leading to inflammation and perpetuation of the condition. Values >312 mOsm/L were found to be 73% sensitive and 92% specific for dry eye disease in one study; [15] however, tear osmolarity values may not be correlated with symptoms [16], and some studies also suggested variability in measurements [17]. However, the variability of the measurements may actually be diagnostic of an unstable tear film and hence dry eye disease. Overall, the role of tear osmolarity in the diagnosis and monitoring of dry eyes is evolving and with further studies will likely play a role in the management of the disease.

Overall, no perfect test or examination finding exists to confirm the diagnosis of dry eye disease. Heterogeneity of patient symptoms, poor correlation of symptoms with exam findings [18] and test results, and variability of exam findings and tests between visits [19, 20] can provide substantial challenges for the ophthalmologist. The overall picture generated from the patient’s symptoms, exam findings, and ancillary testing must be synthesized to provide increased sensitivity and specificity in diagnosis.

The patient’s Schirmer test without anesthesia is >20 mm. You check her tear osmolarity and find it to be 310 mOsm/L.

What Treatment Should Be Initiated?

Due to the poor correlation between symptoms and signs/test findings in dry eye disease, particularly in mild dry eye disease, the patient’s ancillary testing findings should not prevent any interventions. Patients with suggestive symptoms should be placed on trial treatments if other potential etiologies for their symptoms have been ruled out. Our patient should be informed that though the symptoms may improve with lifestyle changes and treatment, the condition is not typically cured but managed.

The initial approach should involve identification of environmental and behavioral risk factors and suggestion of appropriate modifications, as well as initiation of artificial tear supplementation. Scheduling a follow-up visit to assess success of these interventions is prudent, and remaining patient and optimistic is important as disease management can be challenging and punctuated by signs or symptoms that are refractory to treatment.

For aid with desiccating environments, the use of humidifiers may alleviate symptoms caused by excessive heat or air conditioning. Additional care should be taken to improve the dynamics of air movement in an office environment, and work stations may be moved out of the direct line of ducts and vents. Long hours of work on computers should be interrupted by regular breaks. Additionally, placing the monitor below eye level can decrease the interpalpebral aperture, limiting the surface area of the exposed ocular surface, thereby aiding in reduction of tear film evaporation [21].

Smoking cessation counseling should be provided as cigarette use has been found to have adverse effects to the precorneal tear film [22, 23], including the lipid layer [24]. Identifying any offending drugs such as diuretics and anticholinergic medication as discussed above and having patients stop or consider alternatives is important. Discontinuing the Benadryl and following up with her PCP to find other sleep aids that do not have anticholinergic effects will likely be beneficial. Finally, we encourage patients to drink ample amounts of fluids.

Over-the-counter artificial tear supplementation may also be initiated. There are no significant differences between different brands and formulations of artificial tears, and patients can take whichever brand they prefer. While artificial tears without preservatives are preferred, their cost makes them prohibitive unless they become necessary. Artificial tears are generally safe in patients who use them up to four times a day. Ideally, ocular surface lubrication should be done before the patient starts to have symptoms related to ocular surface damage. Instructing the patient to use them three times a day before meals may provide a good aid to remember to use them regularly. Additionally, instructing to instill drops before reading or visual display terminal use may also help prevent exacerbations of symptoms.

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Jan 14, 2018 | Posted by in OPHTHALMOLOGY | Comments Off on Aqueous-Deficient Dry Eye Disease: Evaluation and Management

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