Keratoconjunctivitis sicca

Dry eye syndrome
Classification and external resources
Specialty ophthalmology
ICD-10 H19.3
ICD-9-CM 370.33
MedlinePlus 000426
eMedicine article/1196733 article/1210417
MeSH D007638

Keratoconjunctivitis sicca (KCS), also called dry eye syndrome (DES) or keratitis sicca,[1] is an eye disease caused by eye dryness, which, in turn, is caused by either decreased tear production or increased tear film evaporation. It is found in humans and some animals. KCS is the most common eye disease, affecting 5 - 6% of the population. Prevalence rises to 6 - 9.8% in postmenopausal women,[2] and as high as 34% in the elderly.[3][4] The phrase "keratoconjunctivitis sicca" is Latin, and its translation is "dry [inflammation] of the cornea and conjunctiva".

Signs and symptoms

Typical symptoms of keratoconjunctivitis sicca are dryness, burning[5] and a sandy-gritty eye irritation that gets worse as the day goes on.[1] Symptoms may also be described as itchy, scratchy, stingy or tired eyes.[5][6] Other symptoms are pain, redness, a pulling sensation, and pressure behind the eye.[7][5] There may be a feeling that something, such as a speck of dirt, is in the eye.[5][7] The resultant damage to the eye surface increases discomfort and sensitivity to bright light.[5] Both eyes usually are affected.[8]

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.[7]

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.[5] These activities include prolonged reading, computer usage, driving, or watching television.[5][7] 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.[7][5][8][1] Symptoms reduce during cool, rainy, or foggy weather and in humid places, such as in the shower.[5]

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.[7]

Symptom assessment is a key component of dry eye diagnosis - to the extent that many believe dry eye syndrome to be a symptom-based disease. Several questionnaires have been developed to determine a score that would allow for dry eye diagnosis. The McMonnies & Ho dry eye questionnaire is often used in clinical studies of dry eyes.

Causes

Any abnormality of any one of the three layers of tears produces an unstable tear film, resulting in symptoms of keratitis sicca.[1]

Decreased tear or excessive evaporation

Keratoconjunctivitis sicca is usually due to inadequate tear production from lacrimal hyposecretion or to excessive tear evaporation.[1][5] The aqueous tear layer is affected, resulting in aqueous tear deficiency (ATD).[1] The lacrimal gland does not produce sufficient tears to keep the entire conjunctiva and cornea covered by a complete layer.[5] This usually occurs in people who are otherwise healthy. Increased age is associated with decreased tearing.[1] This is the most common type found in postmenopausal women.[5][9]

Causes include idiopathic, congenital alacrima, xerophthalmia, lacrimal gland ablation, and sensory denervation.[1] In rare cases, it may be a symptom of collagen vascular diseases, including relapsing polychondritis, rheumatoid arthritis, granulomatosis with polyangiitis, and systemic lupus erythematosus.[1][5][10][11] Sjögren's syndrome and other autoimmune diseases are associated with aqueous tear deficiency.[1][5] 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.[1][5][8][7] Infiltration of the lacrimal glands by sarcoidosis or tumors, or postradiation fibrosis of the lacrimal glands can also cause this condition.[1] Recent attention has been paid to the composition of tears in normal or dry eye individuals. Only a small fraction of the estimated 1543 proteins in tears are differentially deficient or upregulated in dry eye, one of which is lacritin.[12][13] Topical lacritin promotes tearing in rabbit preclinical studies.[14] Also, topical treatment of eyes of dry eye mice (Aire knockout mouse model of dry eye) restored tearing, and suppressed both corneal staining and the size of inflammatory foci in lacrimal glands.[15]

Additional causes

Aging is one of the most common causes of dry eyes because tear production decreases with age.[7] Several classes of medications (both prescription and OTC) have been hypothesized as a major cause of dry eye, especially in the elderly. Particularly, cholinergic medications that also cause dry mouth are believed to promote dry eye.[16] Dry eye may also 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.[17][18]

About half of all people who wear contact lenses complain of dry eyes.[7] 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.[7] 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.[19][20][21] The connection between this loss in nerve sensitivity and tear production is the subject of current research.[22]

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.[7] The corneal nerves stimulate tear secretion.[7] Dry eyes caused by these procedures usually resolves after several months, but it can be permanent.[8] Persons who are thinking about refractive surgery should consider this.[7]

An eye injury or other problem with the eyes or eyelids, such as bulging eyes or a drooping eyelid can cause keratoconjunctivitis sicca.[6] Disorders of the eyelid can impair the complex blinking motion required to spread tears.[8] Eye injury or disease leading to Boehm Syndrome may be exacerbated by dry eyes.

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.[1]

Pathophysiology

Having dry eyes for a while can lead to tiny abrasions on the surface of the eyes.[6] In advanced cases, the epithelium undergoes pathologic changes, namely squamous metaplasia and loss of goblet cells.[1] Some severe cases result in thickening of the corneal surface, corneal erosion, punctate keratopathy, epithelial defects, corneal ulceration (sterile and infected), corneal neovascularization, corneal scarring, corneal thinning, and even corneal perforation.[1][5]

Diagnosis

Dry eyes can usually be diagnosed by the symptoms alone.[5] Tests can determine both the quantity and the quality of the tears.[8] A slit lamp examination can be performed to diagnose dry eyes and to document any damage to the eye.[1][5]

A Schirmer's test can measure the amount of moisture bathing the eye.[5] This test is useful for determining the severity of the condition.[7] A five-minute Schirmer's test with and without anesthesia using a Whatman #41 filter paper 5 mm wide by 35 mm long is performed. For this test, wetting under 5 mm with or without anesthesia is considered diagnostic for dry eyes.[1]

If the results for the Schirmer's test are abnormal, a Schirmer II test can be performed to measure reflex secretion.In this test, the nasal mucosa is irritated with a cotton-tipped applicator, after which tear production is measured with a Whatman #41 filter paper. For this test, wetting under 15 mm after five minutes is considered abnormal.[1]

A tear breakup time (TBUT) test measures the time it takes for tears to break up in the eye.[7] The tear breakup time can be determined after placing a drop of fluorescein in the cul-de-sac.[1]

A tear protein analysis test measures the lysozyme contained within tears. In tears, lysozyme accounts for approximately 20 to 40 percent of total protein content.[1]

A lactoferrin analysis test provides good correlation with other tests.[1]

The presence of the recently described molecule Ap4A, naturally occurring in tears, is abnormally high in different states of ocular dryness. This molecule can be quantified biochemically simply by taking a tear sample with a plain Schirmer test. Utilizing this technique it is possible to determine the concentrations of Ap4A in the tears of patients and in such way diagnose objectively if the samples are indicative of dry eye.[23]

The Tear Osmolarity Test has been proposed as a test for dry eye disease.[24] Tear osmolarity may be a more sensitive method of diagnosing and grading the severity of dry eye compared to corneal and conjunctival staining, tear break-up time, Schirmer test, and meibomian gland grading.[25] Others have recently questioned the utility of tear osmolarity in monitoring dry eye treatment.[13]

Prevention

There is no way to prevent keratoconjunctivitis sicca. Complications can be prevented by use of wetting and lubricating drops and ointments.[26]

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.[27]

Dry eyes can be exacerbated by smoky 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.[27] Rubbing one's eyes can irritate them further, so should be avoided.[8] Conditions such as blepharitis can often co-exist and paying particular attention to cleaning the eyelids morning and night with mild soaps and warm compresses can improve both conditions.[27]

Environmental control

Dry, drafty environments and those with smoke and dust should be avoided.[5] 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.[8] Using a humidifier, especially in the winter, can help by adding moisture to the dry indoor air.[8][27][5][6]

Rehydration

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

Application of artificial tears every few hours[5] 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[28] has demonstrated that this modality is more effective than artificial tears in a randomized control study. A 2013 Cochrane review found mixed results when comparing autologous serum eye drops to artificial tears or saline.[29] Evidence from the examined trials showed that autologous serum eye drops resulted in better patient-reported symptoms and improved TBUT, but did not result in improvements in aqueous tear production. No positive effect was observed from ocular surface tests and staining.

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 never be used with contact lenses.[1] Specially designed glasses that form a moisture chamber around the eye may be used to create additional humidity.[8]

Medication

Inflammation occurring in response to tears film hypertonicity can be suppressed by mild topical steroids or with topical immunosuppressants such as Restasis (ciclosporin).[30][31] Elevated levels of tear NGF can be decreased with 0.1% prednisolone.[1]

Diquafosol, an agonist of the P2Y2 purinogenic receptor, is approved in Japan for managing dry eye disease by promoting tear secretion.

Fish and ω−3 fatty acids consumption

Consumption of dark fleshed fish containing dietary omega-3 fatty acids is associated with a decreased incidence of dry eyes syndrome in women.[32] This finding is consistent with postulated biological mechanisms.[32] Early experimental work on omega-3 has shown promising results when used in a topical application[33] or given orally.[34] A randomized, double-masked study published in 2013 to evaluate the effects of a triglyceride of DHA (Omega-3; Brudy Sec 1.5), showed significant results compared to other methods that are being used.[35]

Ciclosporin

Topical ciclosporin (topical cyclosporin A, tCSA) 0.05% ophthalmic emulsion is an immunosuppressant.[1] The drug decreases surface inflammation.[8] In a trial involving 1200 people, Restasis increased tear production in 15% of people, compared to 5% with placebo.[7]

It should not be used while wearing contact lenses,[1] during eye infections[7] or in people with a history of herpes virus infections.[8] Side effects include burning sensation (common),[7] redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.[1][7] Long term use of cyclosporin at high doses is associated with an increased risk of cancer.[36][37]

Cheaper generic alternatives are available in some countries.[38]

Conserving tears

There are methods that allow both natural and artificial tears to stay longer.[8]

In each eye, there are two puncta[39] — little openings that drain tears into the tear ducts.[7] There are methods to partially or completely close the tear ducts.[8] This blocks the flow of tears into the nose, and thus more tears are available to the eyes.[5] Drainage into either one or both puncta in each eye can be blocked.

Punctal plugs are inserted into the puncta to block tear drainage.[7] For people who have not found dry eye relief with drugs, punctal plugs may help.[7] They are reserved for people with moderate or severe dry eye when other medical treatment has not been adequate.[7]

If punctal plugs are effective, thermal[8] or electric[1] cauterization of puncti can be performed. In thermal cauterization, a local anesthetic is used, and then a hot wire is applied.[8] This shrinks the drainage area tissues and causes scarring, which closes the tear duct.[8]

Other

Heating systems that try to unblock the oil glands in the eye has some preliminary evidence of benefit.[40]

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.[5]

Prognosis

Keratoconjunctivitis sicca usually is a chronic problem.[8] Its prognosis shows considerable variance, depending upon the severity of the condition. Most people have mild-to-moderate cases, and can be treated symptomatically with lubricants. This provides an adequate relief of symptoms.[1]

When dry eyes symptoms are severe, they can interfere with quality of life.[7] People sometimes feel their vision blurs with use, or severe irritation to the point that they have trouble keeping their eyes open or they may not be able to work or drive.[7][5]

Epidemiology

Keratoconjunctivitis sicca is relatively common within the United States, especially so in older patients.[1] Specifically, the persons most likely to be affected by dry eyes are those aged 40 or older.[8] Keratoconjunctivitis sicca is estimated to affect 10% to 20% of adults, with 1 to 4 million aged 65 to 84 affected in the United States.[41]

While persons with autoimmune diseases have a high likelihood of having dry eyes, most persons with dry eyes do not have an autoimmune disease.[8] Instances of Sjögren syndrome and keratoconjunctivitis sicca associated with it are present much more commonly in women, with a ratio of 9:1. In addition, milder forms of keratoconjunctivitis sicca also are more common in women.[1] This is partly because hormonal changes, such as those that occur in pregnancy, menstruation, and menopause, can decrease tear production.[7][8]

In areas of the world where malnutrition is common, vitamin A deficiency is a common cause. This is rare in the United States.[26]

Racial predilections do not exist for this disease.[1]

Other animals

Among other animals, keratoconjunctivitis sicca occurs in dogs, cats, and horses.[4]

Dogs

Keratoconjunctivitis sicca is common in dogs. Most cases are caused by a genetic predisposition, but chronic conjunctivitis, canine distemper, and drugs such as sulfasalazine and trimethoprim-sulfonamide also cause the disease.[42] Symptoms include eye redness, a yellow or greenish discharge, ulceration of the cornea, pigmented cornea, and blood vessels on the cornea. Diagnosis is made by measuring tear production with a Schirmer tear test. Less than 15 milliliters of tears produced in a minute is abnormal.[42]

Tear replacers are a mainstay of treatment, preferably containing methylcellulose or carboxymethyl cellulose.[42] Ciclosporin stimulates tear production and acts as a suppressant on the immune-mediated processes that cause the disease. Topical antibiotics and corticosteroids are sometimes used to treat secondary infections and inflammation. A surgery known as parotid duct transposition is used in some extreme cases where medical treatment has not helped. This redirects the duct from the parotid salivary gland to the eye. Saliva replaces the tears. Dogs suffering from cherry eye should have the condition corrected to help prevent this disease.

Commonly affected breeds include:

Cats

Keratoconjunctivitis sicca is uncommon in cats. Most cases seem to be caused by chronic conjunctivitis, especially secondary to feline herpesvirus.[42] Diagnosis, symptoms, and treatment are similar to those for dogs.

See also

References

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  2. ↑ Schaumberg DA, Sullivan DA, Buring JE, Dana MR (August 2003). "Prevalence of dry eye syndrome among US women". American Journal of Ophthalmology 136 (2): 318–26. doi:10.1016/S0002-9394(03)00218-6. PMID 12888056.
  3. ↑ Lin PY, Cheng CY, Hsu WM, et al. (May 2005). "Association between symptoms and signs of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study". Investigative Ophthalmology & Visual Science 46 (5): 1593–8. doi:10.1167/iovs.04-0864. PMID 15851556.
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  30. ↑ Tatlipinar S, Akpek E (2005). "Topical cyclosporine in the treatment of ocular surface disorders". Br J Ophthalmol 89 (10): 1363–7. doi:10.1136/bjo.2005.070888. PMC 1772855. PMID 16170133.
  31. ↑ Barber L, Pflugfelder S, Tauber J, Foulks G (2005). "Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years". Ophthalmology 112 (10): 1790–4. doi:10.1016/j.ophtha.2005.05.013. PMID 16102833.
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  38. ↑ "Sun Pharma Product List". Sun Pharma. Archived from the original on 2007-02-13. Retrieved 2006-11-27.
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  42. 1 2 3 4 5 Gelatt, Kirk N. (ed.) (1999). Veterinary Ophthalmology (3rd ed.). Lippincott, Williams & Wilkins. ISBN 0-683-30076-8.

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