Eye disease: Keratoconjunctivitis sicca

Definition

Keratoconjunctivitis sicca (KCS), also called keratitis sicca,[1] sicca syndrome,[1] xerophthalmia,[1] dry eye syndrome (DES),[1] or simply dry eyes,[1] is an eye disease caused by decreased tear production or increased tear film evaporation commonly found in humans and some animals[2]. The phrase "keratoconjunctivitis sicca" is Latin, and its literal translation is "dryness of the cornea and conjunctiva".

Symptoms

Typical symptoms of keratoconjunctivitis are dryness, burning and a sandy-gritty eye irritation that gets worse as the day goes on. Symptoms may also be described as itchy, scratchy,stingyor tired eyes. Other symptoms are pain, redness, a pulling sensation, and pressure behind the eye. There may be a feeling that something,such as a speck of dirt, is in the eye. The resultant damage to the eye surface increases discomfort and sensitivity to bright light. Both eyes usually are affected.

There may also be a stringy discharge from the eyes. Although it may seem strange, dry eye can cause the eyes to water. This can happen because the eyes are irritated. One may experience excessive tearing in the same way as one would if something got into the eye. These reflex tears will not necessarily make the eyes feel better. This is because they are the watery type that are produced in response to injury, irritation, or emotion. They do not have the lubricating qualities necessary to prevent dry eye.

Because blinking coats the eye with tears, symptoms are worsened by activities in which the rate of blinking is reduced due to prolonged use of the eyes. These activities include prolonged reading, computer usage, driving, or watching television. Symptoms increase in windy, dusty or smoky (including cigarette smoke) areas, in dry environments, high altitudes including airplanes, on days with low humidity, and in areas where an air conditioner (especially in a car), fan,heater, or even a hair dryer is being used. Symptoms reduce during cool, rainy, or foggy weather and in humid places, such as in the shower.

Most people who have dry eyes experience mild irritation with no long-term effects. However, if the condition is left untreated or becomes severe, it can produce complications that can cause eye damage, resulting in impaired vision or (rarely) in the loss of vision.

Causes

Any abnormality of any one of the three layers of tears produces an unstable tear film, resulting in symptoms of keratitis sicca.

Deficient tear production

Keratoconjunctivitis sicca is usually due to inadequate tear production. The aqueous tear layer is affected, resulting in aqueous tear deficiency (ATD) or lacrimal hyposecretion.The lacrimal gland does not produce sufficient tears to keep the entire conjunctiva and cornea covered by a complete layer. This usually occurs in people who are otherwise healthy. Increased age is associated with decreased tearing. This is the most common type found in postmenopausal women.

Causes include idiopathic, congenital alacrima, xerophthalmia, lacrimal gland ablation, and sensory denervation. In rare cases, it may be a symptom of collagen vascular diseases, including rheumatoid arthritis, Wegener's granulomatosis, and systemic lupus erythematosus. Sjögren's syndrome and autoimmune diseases associated with Sjögren's syndrome are also conditions associated with aqueous tear deficiency. Drugs such as isotretinoin, sedatives, diuretics,tricyclic antidepressants, antihypertensives, oral contraceptives, antihistamines, nasal decongestants,beta-blockers, phenothiazines, atropine, and pain relieving opiates such as morphine can cause or worsen this condition. Infiltration of the lacrimal glands by sarcoidosis or tumors, or postradiation fibrosis of the lacrimal glands can also cause this condition.

Abnormal tear composition

Keratoconjunctivitis sicca can also be caused by abnormal tear composition resulting in rapid evaporation^[3] or premature destruction of the tears.^[1] When caused by rapid evaporation, it is termed evaporative dry eyes.^[3] In this, although the tear gland produces a sufficient amount of tears, the rate of evaporation of the tears is too rapid.^[3] There is a loss of water from the tears that results in tears that are too "salty" or hypertonic. As a result, the entire conjunctiva and cornea cannot be kept covered with a complete layer of tears during certain activities or in certain environments.^[3]

Additional causes

Aging is one of the most common causes of dry eyes.^[5] This is because tear production decreases with age.^[5] It may be caused by thermal or chemical burns, or (in epidemic cases) by adenoviruses. A number of studies have found that diabetics are at increased risk for the disease.^[8][9]

About half of all people who wear contact lenses complain of dry eyes.^[5] There are two potential connections between contact usage and dry eye. Traditionally, it was believed that soft contact lenses, which float on the tear film that covers the cornea, absorb the tears in the eyes.^[5] However, it is also now known that contact usage damages corneal nerve sensitivity, which subsequently may lead to decreased lacrimal gland tear production and dry eye. The effect of contact on corneal nerve sensitivity is well established for hard contacts as well as soft and rigid gas permeable^[10][11][12]. The connection between this loss in nerve sensitivity and tear production is the subject of current research ^[13].

Dry eyes also occurs or gets worse after LASIK and other refractive surgeries, in which the corneal nerves are cut during the creation of a corneal flap.^[5] The corneal nerves stimulate tear secretion.^[5] Dry eyes caused by these procedures usually resolves after several months.^[6] Persons who are thinking about refractive surgery should consider this.^[5]

An eye injury or other problem with the eyes or eyelids, such as bulging eyes or a drooping eyelid can cause keratoconjunctivitis sicca.^[4] Disorders of the eyelid can impair the complex blinking motion required to spread tears.^[6]

Abnormalities of the lipid tear layer caused by blepharitis and rosacea, and abnormalities of the mucin tear layer caused by vitamin A deficiency, trachoma, diphtheric keratoconjunctivitis, mucocutaneous disorders and certain topical medications are causes of keratoconjunctivitis sicca.^[1]

Persons with keratoconjunctivitis sicca have elevated levels of tear nerve growth factor (NGF).^[1] It is possible that this ocular surface NGF plays an important role in ocular surface inflammation associated with dry eyes.

Treatment

A variety of approaches can be taken to treatment. These can be summarised as: avoidance of exacerbating factors, tear stimulation and supplementation, increasing tear retention, and eyelid cleansing and treatment of eye inflammation.^[15]

General measures

Dry eyes can be exacerbated by smokey environments, dust and air conditioning and by our natural tendency to reduce our blink rate when concentrating. Purposefully blinking, especially during computer use and resting tired eyes are basic steps that can be taken to minimise discomfort.^[15] Rubbing one's eyes can irritate them further, so should be avoided ^[6]. Conditions such as blepharitis can often co-exist^[15] and paying particular attention to cleaning the eyelids morning and night with mild shampoos and warm compresses can improve both conditions.

Environmental control

Dry, drafty environments and those with smoke and dust should be avoided.^[3] This includes avoiding hair dryers, heaters, air conditioners or fans, especially when these devices are directed toward the eyes.^[6] 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 ^[6]. Using a humidifier,^[3][4] especially in the winter,^[4] can help by adding moisture to the dry indoor air^[6].^[15].

Rehydration

For mild and moderate cases, supplemental lubrication is the most important part of treatment.^[1]

Artificial tears

Application of artificial tears every few hours^[3] can provide temporary relief.

Autologous serum eye drops

None of the commercially available artificial tear preparations include essential tear components such as epidermal growth factor, hepatocyte growth factor, fibronectin, neurotrophic growth factor, and vitamin A-all of which have been shown to play important roles in the maintenance of a healthy ocular surface epithelial milieu. Autologous serum eye drops contain these essential factors. However, there is some controversy regarding the efficacy of this treatment. At least one study (PubMed) has demonstrated that this modality is more effective than artificial tears in a randomized control study.

Additional options

Lubricating tear ointments can be used during the day, but they generally are used at bedtime due to poor vision after application.^[1] They contain white petrolatum, mineral oil, and similar lubricants.^[1] They serve as a lubricant and an emollient.^[1] Application requires pulling down the eyelid and applying a small amount (0.25 in) inside.^[1] Depending on the severity of the condition, it may be applied from every hour to just at bedtime.^[1] It should not be used with contact lenses.^[1] Specially designed glasses that form a moisture chamber around the eye may be used to create additional humidity.^[6]

Medication

Inflammation occurring in response to tears film hypertonicity can be suppressed by mild topical steroids or with topical immunosuppressants such as ciclosporin.^[16][17] Elevated levels of tear NGF can be decreased with 0.1% prednisolone.^[1]

Fish consumption and omega-3 fatty acids

Consumption of dark fleshed fish containing dietary omega-3 fatty acids is associated with a decreased incidence of dry eyes syndrome in women.^[18] This finding is consistent with postulated biological mechanisms.^[18]. Early experimental work on omega-3 has shown promising results when used in a topical application ^[19] or given orally.^[20].

Restasis

Topical cyclosporine A (tCSA) 0.05% ophthalmic emulsion is an immunosuppressant, marketed in the United States by Allergan under the trade name Restasis^[1]. Approved as a prescription product by the U.S. Food and Drug Administration^[5] in 2002, the drug decreases surface inflammation^[6]. It is thought to work through inhibition^[21] of transcription factors required for cytokine production and T-lymphocyte maturation.^[22] In a trial involving 1200 people, Restasis increased tear production in 15% of people, compared to 5% with placebo^[5].

Usually, 1 gtt (drop) of Restasis is instilled in each eye twice a day, 12 hours apart.^[1] It should not be used while wearing contact lenses,^[1] during eye infections ^[5] or in people with a history of herpes virus infections^[6]. Side effects include burning sensation (common)^[5], redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.^[1][5] Long term use of ciclosporin at high doses is associated with an increased risk of cancer^[23][24].

Generic alternatives

Cheaper generic alternatives to Restasis are available in some countries. In India, it is marketed as Cyclomune by Sun Pharma.^[25]

Conserving tears

There are methods that allow both natural and artificial tears to stay longer.^[6]

Blocking tear drainage

In each eye, there are two puncta^[26] — little openings that drain tears into the tear ducts^[5]. There are methods to partially or completely close the tear ducts.^[6] This blocks the flow of tears into the nose, and thus more tears are available to the eyes.^[3]

Punctal plugs

Punctal plugs are inserted into the puncta to block tear drainage.^[5] For people who have not found dry eye relief with drugs, punctal plugs may help.^[5] They are reserved for people with moderate or severe dry eye when other medical treatment has not been adequate.^[5]

Cauterization

If punctal plugs are effective, thermal^[6] or electric^[1] cauterization of puncti can be performed.

In thermal cauterization, a local anesthetic is used, and then a hot wire is applied.^[6] This shrinks the drainage area tissues and causes scarring, which closes the tear duct.^[6]

Customized contact lenses

Persons with severe dry eyes may benefit from the Boston Scleral Lens which is a customized contact lens.^[6] Resting on the sclera, it creates a fluid filled layer over the cornea, thus preventing it from drying.^[6]

Surgery

In severe cases of keratoconjunctivitis sicca, tarsorrhaphy may be performed where the eyelids are partially sewn together. This reduces the palpebral fissure (eyelid separation), ideally leading to a reduction in tear evaporation.

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