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Dry Eye Disease Symptoms, Diagnosis, Treatment

Dry Eye Disease Symptoms/Dry Eye Disease is a common ocular multi factorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface, accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.[rx] Estimated prevalence ranges from about 5% to over 35% in different age groups.[rx]

Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS) is the condition of having dry eyes.^[rx] Other associated symptoms include irritation, redness, discharge, and easily fatigued eyes. Blurred vision may also occur.^[rx] The symptoms can range from mild and occasional to severe and continuous.^[rx] Scarring of the cornea may occur in some cases without treatment.^[rx]

Keratitis sicca Generally used to describe dryness and inflammation of the cornea.
Keratoconjunctivitis sicca Used to describe dry eye that affects both the cornea and the conjunctiva.
Dysfunctional tear syndrome Used to emphasize that inadequate quality of tears can be just as important as inadequate quantity.

Dry Eye Disease Symptoms

Pathophysiology of Dry Eye Disease

There are two main types of dry eye syndrome. The first is a deficiency to the water component of the tears because the lacrimal glands fail to produce enough of the watery component to maintain a healthy tear surface. This is found in those with Sjogren syndrome and autoimmune disorders such as rheumatoid arthritis. The lack of water also can be seen in situations where there is poor closure of the lids or where the lids to not adequately touch the cornea. The second type of dry eye syndrome is caused by a problem with the lipid layer which is produced by the meibomian glands. The top oily surface of the tears slows down the rate of evaporation of the tears. In situations such as meibomian gland dysfunction, the oil is abnormal and does a poor job of stabilizing the tear film, allowing the tears to evaporate more quickly. Dry eyes also can occur when there is an inadequate production of surfactant (mucin) to keep the tears sticking to the front of the cornea.

Causes of Dry Eye Disease

Medications – such as antihistamines, major tranquilizers, diuretics, Parkinson medications and antidepressants.
Skin diseases – on or around the eyelids.
Meibomian gland dysfunction – is a common co-morbidity with thickening of the eyelids, thickened secretions of the oil glands and erythema of the lids.
Laser vision correction – such as LASIK and PRK. This dryness typically lasts for three to four months postop but may last much longer and may even be permanent in some individuals.
Chemical – or thermal burns that scar the conjunctiva.
Allergies – as well as allergy medication.
Computer Vision Syndrome – manifested by decreased blinking when working at computer or video screen.
Excess or insufficient dosages of vitamins – The classic vitamin deficiency associated with dry eyes is a lack of Vitamin A which leads to Bitot spots.
Decreased sensation – in the cornea from long-term contact lens wear, herpes infections, or other causes of a neurotrophic cornea.
Sjogren syndrome – rheumatoid arthritis, lupus, and other autoimmune disorders lead to inflammation causing dryness of the mouth, eyes, and other mucous membranes.
Environmental factors – such as exposure to irritants like chemical fumes, cigarette smoke, drafts from air conditioners or heaters can lead to chronic inflammation of the conjunctiva and dryness eyes; exposure of the eye such as seen in thyroid disease, when the eyelids fail to close after cosmetic surgery, or other causes of exposure keratitis.
Computer use – When working at a computer or using a smartphone or other portable digital device, we tend to blink our eyes less fully and less frequently, which leads to greater tear evaporation and increased risk of dry eye symptoms.
Contact lens wear – Though it can be difficult to determine the exact extent that contact lens wear contributes to dry eye problems, dry eye discomfort is a primary reason why people discontinue contact lens wear.
Aging Dry eye syndrome can occur at any age, but it becomes increasingly more common later in life, especially after age 50.
Menopause Post-menopausal women are at greater risk of dry eyes than men of the same age.
Indoor environment Air conditioning, ceiling fans and forced air heating systems all can decrease indoor humidity and/or hasten tear evaporation, causing dry eye symptoms.
Outdoor environment Arid climates and dry or windy conditions increase dry eye risks.
Frequent flying The air in the cabins of airplanes is extremely dry and can lead to dry eye problems, especially among frequent flyers.
Smoking In addition to dry eyes, smoking has been linked to serious eye problems, including macular degeneration, cataracts and uveitis.
Health conditions Certain systemic diseases — such as diabetes, thyroid-associated diseases, lupus, rheumatoid arthritis and Sjogren’s syndrome — contribute to dry eye problems.
Medications Many prescription and nonprescription medicines — including antihistamines, antidepressants, certain blood pressure medications and birth control pills — increase the risk of dry eye symptoms.
Eyelid problems Incomplete closure of the eyelids when blinking or sleeping — a condition called lagophthalmos, which can be caused by aging or occur after cosmetic blepharoplasty or other causes — can cause severe dry eyes that can lead to a corneal ulcer if left untreated.

Symptoms of Dry Eye Disease

Typical symptoms of dry eye syndrome are

dryness, burning^[rx] and a sandy-gritty eye irritation that gets worse as the day goes on.^[rx]
Symptoms may also be described as itchy, scratchy, stinging or tired eyes.^[rx]^[rx]
Other symptoms are pain, redness, a pulling sensation, and pressure behind the eye.^[rx]^[rx]
There may be a feeling that something, such as a speck of dirt, is in the eye.^[rx]^[rx]
The resultant damage to the eye surface increases discomfort and sensitivity to bright light.^[rx] Both eyes usually are affected.^[rx]
A sensation of having something in your eyes
Difficulty wearing contact lenses
Difficulty with nighttime driving
Watery eyes, which is the body’s response to the irritation of dry eyes
Burning sensation
Itchy eyes
Aching sensations
Heavy eyes
Fatigued eyes
Sore eyes
Dryness sensation
Red eyes
Photophobia
Blurred vision

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Diagnosis of Dry Eye Disease

History and Physical

Dry eye syndrome may have any of the following signs and symptoms:

Stinging, burning, or a feeling of pressure in the eyes. This feeling of pressure may be dull or sharp, and the patient may localize the pain to many different areas around the eyes.
A sandy, gritty, or foreign body sensation is common, with patients commonly rubbing the eyes because of the feeling of a foreign body.
Epiphora or tearing may seem counterintuitive. Watering of the eyes is a sign of irritation, and when the tear film is abnormal and the surfactant is decreased, the eyes water more and can become dryer.
Stringy mucus discharge can be seen in those who stick their fingers in their eyes and pull the mucous out. The more that the patient does this action, the more the stringy mucous occurs.
Pain is a broad term, and sharp and dull pain can be described, which may be localized to some part of the eye, behind the eye, or even around the orbit.
Redness is a common complaint and is often made worse with the rebound effect of vasoconstrictors such as Visine Red Out, Clear Eyes, or Naphcon. All of these decrease redness for the short term by constricting the vessels of the episclera but have a dramatic rebound effect and increased redness after the drops wear off in a relatively short period of time. It is better to treat the irritation rather than the redness.
Blurry vision is a common complaint and may also be described as glare or haloes around lights at night.
A sensation of heavy eyelids or difficulty opening the eyes. As patients rub their eyes because of discomfort, the cornea is damaged leading to mild photophobia and difficulty in keeping the eyes open.
Dryness is a common problem for contact lenses wearers, and irritation may make contact lenses uncomfortable or even impossible to wear.
Tired eyes and a desire to go to sleep is a sign of irritation. Closing the eyes gives substantial relief to most with dry eyes.

Dry eye disease severity grading scheme [rx]

Dry eye severity level	1	2	3	4
Discomfort, severity and frequency	Mild and/or episodic; occurs under environmental stress	Moderate episodic or chronic, stress or no stress	Severe frequent or constant without stress	Severe and/or disabling and constant
Visual symptoms	None or episodic mild fatigue	Annoying and/or activity-limiting episodic	Annoying, chronic and/or constant, limiting activity	Constant and/orpossibly disabling
Conjunctival injection	None to mild	None to mild	+/−	+/++
Corneal staining (severity/location)	None to mild	Variable	Marked central	N/A
Corneal/tear signs	None to mild	Mild debris, ↓ meniscus	Filamentary keratitis, mucus clumping, ○ tear debris	Filamentary keratitis, mucus clumping, ○ tear debris, ulceration
Lid/meibomian glands	MGD variably present	MGD variably present	MGD frequent	Trichiasis, keratinization, symblepharon
Tear film break-up time (seconds)	Variable	≥ 10	≥ 5	Immediate
Schirmer score (measures tear secretion) (mm/5 minutes)	Variable	≥ 10	≥ 5	≥ 2

[rx]

MGD, meibomian gland dysfunction; – not present; + mild; ++ moderate; N/A, not applicable

Treatment of Dry Eye Disease

Treatment of dry eye syndrome is usually taken on a step-wise approach and includes the following:

Preserved artificial tears
Preservative-free artificial tears
Preservative-free artificial tears with sodium hyaluronate
Night-time ointments
Anti-inflammatory agents, including prescription strength 0.05% topical cyclosporine (Restasis), lifitegras (Xiidra), and topical steroids (controversial)
Systemic omega-3 fatty acids
Punctal plugs
Treatment of concomitant lid disease with systemic doxycycline or topical antibiotics (erythromycin, bacitracin/polymyxin, azithromycin)
Moisture goggles
1% cyclosporine and lifitegras increase tear production but can take several weeks to start working. The longer that the patient uses these products, the better the effect. Even stopping for a few days may add months before the patient achieves the same result from the treatment;
Autologous serum drops;
Secretagogues; and
Systemic immunosuppressants.
Drugs to reduce eyelid inflammation – Inflammation along the edge of your eyelids can keep oil glands from secreting oil into your tears. Your doctor may recommend antibiotics to reduce inflammation. Antibiotics for dry eyes are usually taken by mouth, though some are used as eyedrops or ointments.
Eyedrops to control cornea inflammation – Inflammation on the surface of your eyes (cornea) may be controlled with prescription eyedrops that contain the immune-suppressing medication cyclosporine (Restasis) or corticosteroids. Corticosteroids are not ideal for long-term use due to possible side effects.
Eye inserts that work like artificial tears – If you have moderate to severe dry eye symptoms and artificial tears don’t help, another option may be a tiny eye insert that looks like a clear grain of rice. Once a day, you place the hydroxypropyl cellulose (Lacrisert) insert between your lower eyelid and your eyeball. The insert dissolves slowly, releasing a substance that’s used in eyedrops to lubricate your eye.
Tear-stimulating drugs – Drugs called cholinergics (pilocarpine, cevimeline) help increase tear production. These drugs are available as pills, gel or eyedrops. Possible side effects include sweating.
Eyedrops made from your own blood – These are called autologous blood serum drops. They may be an option if you have severe dry eye symptoms that don’t respond to any other treatment. To make these eyedrops, a sample of your blood is processed to remove the red blood cells and then mixed with a salt solution.

Environmental Control

Dry, drafty environments and those with smoke and dust should be avoided.^[rx] This includes avoiding hair dryers, heaters, air conditioners or fans, especially when these devices are directed toward the eyes. Wearing glasses or directing gaze downward, for example, by lowering computer screens can be helpful to protect the eyes when aggravating environmental factors cannot be avoided.^[rx] Using a humidifier, especially in the winter, can help by adding moisture to the dry indoor air.^[rx]^[rx]

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Rehydration

For mild and moderate cases, supplemental lubrication is the most important part of treatment.^[rx]
Application of artificial tears every few hours^[rx] can provide temporary relief. Additional research is necessary to determine whether certain artificial tear formulations are superior to others in treating dry eye.^[rx]

Autologous Serum Eye Drops

A 2017 Cochrane review found mixed results when comparing autologous serum eye drops to artificial tears or saline.^[rx] Evidence from the examined trials showed that autologous serum eye drops may have a small short-term benefit when compared to artificial tears, but there is no evidence of improvement after 2 weeks.^[rx]

Anti-inflammatory Treatment

Even with only moderately severe dry eye, there is an (often subclinical) inflammatory reaction of the ocular surface and the lacrimal gland [rx, rx]. To break the vicious circle of surface damage and inflammation, anti-inflammatory treatment is required in patients with moderate to severe dry eye disease.

Topical Corticosteroids

Randomized, controlled clinical studies have shown that unpreserved corticosteroid eyedrops, instilled over a period of 2 to 4 weeks, improve the symptoms and clinical signs of moderate to severe dry eye disease [rx, rx]. After 2 weeks of treatment, symptoms regressed moderately (43%) or completely (57%).
Corneal fluorescein staining reduced significantly. Patient discomfort and clinical signs remained reduced for several weeks after therapy ceased [rx, rx]. A few patients developed complications with long-term therapy (raised intraocular pressure, cataract), and for this reason corticosteroid eyedrops are recommended only for short-term use [rx]. A cycle of treatment is also useful for testing patients’ response for long-term anti-inflammatory treatment with cyclosporine A.

Anti-inflammatory Treatment

In patients with moderate to severe dry eye disease, anti-inflammatory treatment is necessary to break the vicious circle of surface damage and inflammation.

Topical Cyclosporine A

Cyclosporine A is an immunosuppressant that inhibits the calcineurin–phosphatase pathway by complex formation with cyclophilin, and thus reduces the transcription of T-cell-activating cytokines such as interleukin-2 (IL-2) [rx]. Topical application of cyclosporine A leads to increased production of tear fluid, possibly via local release of parasympathetic neurotransmitters [rx].
In randomized, controlled clinical trials, treatment with 0.05% eyedrops 2 ×/day led to improvement in keratopathy, increased Schirmer test values, reduced symptoms (blurry vision, ocular dryness, foreign body sensation, and epiphora), and a reduction in the use of artificial tears [rx, rx].
This clinical improvement was associated with a reduction in inflammatory cells and inflammatory markers on the ocular surface and an increase in the number of goblet cells in the conjunctiva [rx]. Cyclosporine A eyedrops 0.05% are commercially available as a long-term therapeutic agent in the USA. In Germany, cyclosporine A can be prescribed as extemporaneous product from dispensing pharmacies.

Corticosteroid Eyedrops

Unpreserved corticosteroid eyedrops, instilled over a period of 2 to 4 weeks, improve the symptoms and clinical signs of moderate to severe dry eye disease.

Tacrolimus/Pimecrolimus

Tacrolimus 0.03% eyedrops 1 to 2 ×/day have been successfully used in pilot studies and in small uncontrolled interventional case series in patients with severe dry eye disease. They appear to be as effective as cyclosporine A and are used in patients who cannot tolerate cyclosporine A [rx, rx].
Tacrolimus/pimecrolimus skin ointment has been reported as successfully used on the eyelids 1 to 2 ×/day in treatment-resistant blepharokeratoconjunctivitis [rx].

Tetracyclines

Tetracyclines are bacteriostatic antibiotics with anti-inflammatory effect. They reduce the synthesis and activity of matrix metalloproteinases, the production of interleukin-1 (IL-1) and tumor necrosis factor, collagenase activity, and B-cell activation [rx, rx].
Tetracycline analogs have been successfully used in small controlled studies to treat meibomian gland dysfunction and rosacea [rx, rx]. Dosages varied between 40 and 400 mg/day for doxycycline and between 50 and 100 mg/day for minocycline.
Even at low doses, improvements were seen in tear film stability, tear production, and symptoms [rx]. Because of the significantly higher rate of adverse effects (primarily gastrointestinal and skin problems) at higher dosages, a low dosage for 6 to 12 weeks is recommended [rx, rx].

Macrolides

Azithromycin, in addition to its well-known antibiotic effect, also has anti-inflammatory capacities [rx]. Azithromycin 1% has been successfully used in several small evidence-level-2/3 studies to treat blepharitis and meibomian gland dysfunction [rx, rx].
In addition to improved meibomian gland function and symptoms, a reduction in bacterial colonization of the eyelid margins and normalization of the meibomian gland secretion lipid profile were found [rx, rx].

Omega Fatty Acids

Omega-3 and omega-6 are essential fatty acids for ocular surface homeostasis. They have to be absorbed from food. Omega-3 fatty acids, especially, work by blocking proinflammatory eicosanoids and reducing cytokines through anti-inflammatory activity [rx].
In a randomized, controlled clinical study systemic linoleic acid and gamma-linolenic acid given to 26 patients with dry eye disease reduced ocular surface inflammation, surface staining, and symptoms [rx]. Very recently, omega-3 fatty acid eyedrops have become available, and are currently under investigation.

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Essential Fatty Acids

Essential fatty acids are necessary for health. They cannot be synthesized by vertebrates and must be obtained from dietary sources. Among the essential fatty acids are the 18 carbon omega-6 and omega-3 fatty acids. In a typical western diet, omega-6 fatty acids are consumed 20 to 25 times more than omega-3 fatty acids. Omega-6 fatty acids are precursors of arachidonic acid and certain pro-inflammatory lipid mediators such as prostaglandin E₂ and leukotriene B₄.

Hormonal Therapy

Receptors for androgens, estrogens, progesterone and prolactin have been identified in several ocular tissues, including the lacrimal gland and meibomian glands.[rx,rx] Experimental and human studies have demonstrated that adequate androgen, prolactin and estrogen levels are essential for normal lacrimal gland function and structural organization.[rx,rx] Administration of topically applied androgen and estrogen steroid hormones for 3–4 months has also been found to show clinical improvement in the form of increased tear production TBUT and lipid layer thickness with corresponding symptomatic relief.

Nerve Growth Factor (NGF)

NGF has been observed to increase ocular surface sensitivity, inhibit inflammatory reactions and regulate tear film production.[rx] Thus, NGF seems to a play a pivotal role in the pathophysiology of DE and may be a promising therapeutic option.[rx]

Autologous Serum

Autologous and umbilical cord serum contains substances that support the proliferation, differentiation, and maturation of the normal ocular surface epithelium[rx] and therefore, finds application in the treatment of severe DE.[rx]

Acupuncture

The use of acupuncture as a treatment for eye disease is based on the claims that acupuncture modulates autonomic nervous system and immune system,[rx,rx] which in turn might regulate lacrimal gland function. It therefore seems pertinent to evaluate the effectiveness of acupuncture as a treatment for DE. To date, more than 70 papers have examined the effect of acupuncture in treating DE. While some authors have suggested that acupuncture can influence lacrimal gland secretions,[rx] others have postulated that it can alleviate pain intensity (or increase pain threshold).[rx]

Unblocking Oil Glands

Warm compresses or eye masks used daily can help clear up blocked oil glands. A thermal pulsation device is another way to unclog the oil glands, but it is unclear whether this method provides any advantage over warm compresses.

Using Light Therapy and Eyelid Massage

A technique called intense-pulsed light therapy followed by massage of the eyelids has proven to help people with severe dry eyes.

Prevention

If you experience dry eyes, pay attention to the situations that are most likely to cause your symptoms.

Avoid air blowing in your eyes – Don’t direct hair dryers, car heaters, air conditioners or fans toward your eyes.
Add moisture to the air – In winter, a humidifier can add moisture to dry indoor air.
Consider wearing wraparound sunglasses or other protective eyewear – Safety shields can be added to the tops and sides of eyeglasses to block wind and dry air. Ask about shields where you buy your eyeglasses.
Take eye breaks during long tasks – If you’re reading or doing another task that requires visual concentration, take periodic eye breaks. Close your eyes for a few minutes. Or blink repeatedly for a few seconds to help spread your tears evenly over your eyes.
Be aware of your environment – The air at high altitudes, in desert areas and in airplanes can be extremely dry. When spending time in such an environment, it may be helpful to frequently close your eyes for a few minutes at a time to minimize evaporation of your tears.
Position your computer screen below eye level – If your computer screen is above eye level, you’ll open your eyes wider to view the screen. Position your computer screen below eye level so that you won’t open your eyes as wide. This may help slow the evaporation of your tears between eye blinks.
Stop smoking and avoid smoke – If you smoke, ask your doctor for help devising a quit-smoking strategy that’s most likely to work for you. If you don’t smoke, stay away from people who do. Smoke can worsen dry eyes symptoms.
Use artificial tears regularly – If you have chronic dry eyes, use eyedrops even when your eyes feel fine to keep them well-lubricated.