Keratoconjunctivitis sicca

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Synonyms and keywords: KCS; Keratitis sicca; sicca syndrome; dry eye syndrome; DES; dry eyes

Overview

Keratoconjunctivitis sicca (KCS), also called keratitis sicca,

sicca syndrome, 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]. Keratoconjunctivitis sicca is Latin and its literal translation is "dryness of the cornea and conjunctiva".  It may be helpful to know that "sicca" is part of the English word "desiccate."

When found in association with Xerostomia and polyarthritis, it is called Sjogren's syndrome.

Symptoms

Typical symptoms of keratoconjunctivitis are dryness, burning[3] and a sandy-gritty eye irritation that gets worse as the day goes on.[1] Symptoms may also be described as itchy,[3] scratchy,[4] stingy[3] or tired[3] eyes. Other symptoms are pain,[5] redness,[5] a pulling sensation,[3] and pressure behind the eye[3]. There may be a feeling that something,[3] such as a speck of dirt,[5] is in the eye. The resultant damage to the eye surface increases discomfort and sensitivity to bright light.[3] Both eyes usually are affected.[6]

There may also be a stringy discharge from the eyes.[5] Although it may seem strange, dry eye can cause the eyes to water.[5] This can happen because the eyes are irritated.[5] One may experience excessive tearing in the same way as one would if something got into the eye.[5] These reflex tears will not necessarily make the eyes feel better.[5] This is because they are the watery type that are produced in response to injury, irritation, or emotion.[5] They do not have the lubricating qualities necessary to prevent dry eye.[5]

Because blinking coats the eye with tears,[5] symptoms are worsened by activities in which the rate of blinking is reduced due to prolonged use of the eyes[3]. These activities include prolonged reading,[1] computer usage,[1][5][3] driving,[3] or watching television[5][3]. Symptoms increase in windy,[5] dusty[5][3] or smoky (including cigarette smoke[5]) areas,[1][3] in dry environments[1][3], high altitudes including airplanes,[6] on days with low humidity,[3] and in areas where an air conditioner[5] (especially in a car[3]), fan,[3] heater,[3] or even a hair dryer[5] is being used. Symptoms reduce during cool, rainy, or foggy weather and in humid places, such as in the shower.[3]

Most people who have dry eyes experience mild irritation with no long-term effects.[5] However, if the condition is left untreated or becomes severe, it can produce complications that can cause eye damage,[5] resulting in impaired vision or (rarely[3]) in the loss of vision[5].

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. McMonnies & Ho dry eye questionnaire is the one that is often used in clinical studies of dry eyes. There are 14 questions that can give a score from 0 to 45. Scores above 14.5 are consistent with dry eye diagnosis.

Pathophysiology

Having dry eyes for a while can lead to tiny abrasions on the surface of the eyes.[4] 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,[3] corneal erosion,[1] punctate keratopathy,[1] epithelial defects,[1] corneal ulceration (sterile and infected),[1] corneal neovascularization,[1] corneal scarring,[1][3] corneal thinning,[1] and even corneal perforation[1].

Causes

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

Deficient tear production

Keratoconjunctivitis sicca is usually due to inadequate tear production.[1][3] The aqueous tear layer is affected, resulting in aqueous tear deficiency (ATD) or lacrimal hyposecretion.[1] The lacrimal gland does not produce sufficient tears to keep the entire conjunctiva and cornea covered by a complete layer.[3] 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.[3][7]

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 rheumatoid arthritis[3], Wegener's granulomatosis, and systemic lupus erythematosus.[1] Sjögren's syndrome[3] and autoimmune diseases associated with Sjögren's syndrome are also conditions associated with aqueous tear deficiency.[1] Drugs such as isotretinoin,[3] sedatives,[3][6] diuretics,[3] tricyclic antidepressants,[6] antihypertensives,[3] oral contraceptives,[1][3] antihistamines,[1][5][3] nasal decongestants,[5] beta-blockers,[1] phenothiazines,[1] atropine,[1], and pain relieving opiates such as morphine[6] 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.[1]

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]

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]

About half of all people who wear contact lenses complain of dry eyes.[5] This is because soft contact lenses, which float on the tear film that covers the cornea, absorb the tears in the eyes.[5] 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]

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]

Diagnosis

Dry eyes can usually be diagnosed by the symptoms alone.[3] Tests can determine both the quantity and the quality of the tears.[6] A slit lamp examination can be performed to diagnose dry eyes and to document any damage to the eye.[1][3]

A Schirmer's test can measure the amount of moisture bathing the eye.[3] This test is useful for determining the severity of the condition.[5] 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.[1] 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.[1] 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.[1] 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.[5] 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.[1] 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]

Recently it was described a molecule - Ap4A- which is intrinsic component of the tears. The presence of this molecule is abnormally high in different states of the ocular dryness. This molecule could quantifyied biochemically simply taking one tear sample with a plain Schirmer test. Utilizing this technique is possible to determine the concentrations of Ap4A in the tear of the patients and such way to diagnose in an objective way if the samples are corresponding to dry eye[10].

Treatment

Purposefully blinking more often, and resting the eyes are basic steps one can take.[4] Rubbing one's eyes can irritate them further, so it should be avoided.[6] Persons with dry eyes caused by an eyelid disorder should undergo treatment for the underlying condition.[6]

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.

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]

Environmental control

Avoiding dry or drafty environments, or environments with smoke and dust, may help.[3] This also includes avoiding environmental aggravation caused by hair dryers, heaters, air conditioners or fans, especially when directed toward the eyes.[6] Wearing wraparound glasses when outside can help reduce the drying effects of the wind.[6]

Using a humidifier,[3][4] especially in the winter,[4] adds moisture[6] to dry indoor air. Specially designed glasses that form a moisture chamber around the eye may be used to create additional humidity.[6]

Supplementation

Consumption of dietary omega-3 fatty acids is associated with a decreased incidence of dry eyes syndrome in women.[11] This finding is consistent with postulated biological mechanisms.[11]

Medication

Inflammation occurring in response to tears film hypertonicity can be suppressed by mild topical steroids or with topical immunosuppressants such as cyclosporine.[12][13] Elevated levels of tear NGF can be decreased with 0.1% prednisolone.[1]

Restasis

Topical cyclosporine A (tCSA) 0.05% ophthalmic emulsion, marketed in the United States by Allergan under the trade name Restasis[1], is the only prescription product approved for chronic dry eyes.[5] Approved by the U.S. Food and Drug Administration in 2002 for this indication[5], the drug decreases inflammation[6] on the eye surface. Cyclosporine appears to work since the chronic inflammation of the ocular surface is mediated mainly by T-lymphocytes and cyclosporine’s proposed mechanism of action in immunosuppression is through T-lymphocyte inhibition[14] through “binding an intracellular protein that ultimately controls transcription factors required for cytokine production and T-lymphocyte maturation”.[15]

It increases healthy tear production,[6] which may be reduced because of inflammation on the eye surface.[5] In a clinical trial involving 1,200 individuals, Restasis increased tear production in 15 percent of patients, compared with 5 percent of patients in the placebo group.[5]

Usually, 1 gutt (drop) of Restasis is instilled in each eye twice a day, 12 hours apart.[1] It should not be used when wearing contact lenses,[1] or by persons with eye infections[5] or hypersensitivity[5] to the ingredients. It has not been tested in people with herpes viral infections of the eye,[5] and it should not be used by anyone with a history[6] of such an infection. The most common side effect is a burning sensation.[5] Other side effects may be eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.[1][5]

Generic alternatives

Cheaper generic alternatives to Restasis are available in some countries. In India, it is marketed as Cyclomune by Sun Pharma.[16]

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[17] — 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, the eyelids may be partially sewn together to reduce tear evaporation.[3]

Prognosis

Keratoconjunctivitis sicca usually is a chronic problem.[6] Its prognosis shows considerable variance, depending upon the severity of the condition.[1] Most patients have mild-to-moderate cases, and can be treated symptomatically with lubricants.[1] This provides an adequate relief of symptoms.[1]

When dry eyes symptoms are severe, they can interfere with quality of life.[5] People sometimes feel their vision blurs with use,[3] or severe irritation[3] to the point that they have trouble keeping their eyes open[5] or they may not be able to work or drive[5].

Prevention

There is no way to prevent keratoconjunctivitis sicca.[18] Complications can be prevented by use of wetting and lubricating drops and ointments.[18]

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.[6]

While persons with autoimmune diseases have a have a high likelihood of having dry eyes, most persons with dry eyes do not have an autoimmune disease.[6] Instances of Sjögren syndrome and keratoconjunctivitis sicca associated with it are present much more commonly in women, with a ratio of 9:1.[1] In addition, milder forms of keratoconjunctivitis sicca also are more common in women.[1] This is partly because hormonal changes,[6] such as those that occur in pregnancy, menstruation, and menopause,[6] can decrease tear production.[5]

In areas of the world where malnutrition is common, vitamin A deficiency is a common cause.[18] This is rare in the United States.[18]

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

See also

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 1.38 1.39 1.40 1.41 1.42 1.43 1.44 1.45 1.46 1.47 1.48 1.49 1.50 1.51 1.52 1.53 1.54 1.55 1.56 1.57 1.58 1.59 1.60 1.61 1.62 1.63
  2. "Keratoconjunctivitis, Sicca". The Merck Veterinary Manua. Merck & Co., Inc. Retrieved 2006-11-18.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 3.24 3.25 3.26 3.27 3.28 3.29 3.30 3.31 3.32 3.33 3.34 3.35 3.36 3.37 3.38 3.39 3.40 3.41 3.42 3.43 3.44 3.45 3.46 3.47 "Keratoconjunctivitis Sicca". The Merck Manual, Home Edition. Merck & Co., Inc. 2003-02-01. Retrieved 2006-11-12.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 "Dry eyes". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. 2006-10-04. Retrieved 2006-11-16.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 5.26 5.27 5.28 5.29 5.30 5.31 5.32 5.33 5.34 5.35 5.36 5.37 5.38 5.39 5.40 5.41 5.42 5.43 5.44 5.45 5.46 5.47 5.48 Meadows, Michelle (2005). "Dealing with Dry Eye". FDA Consumer Magazine. U.S. Food and Drug Administration. Retrieved 2006-11-16. Unknown parameter |month= ignored (help); More than one of |author= and |last= specified (help); External link in |work= (help)
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 "Dry eyes". Mayo Clinic. Mayo Foundation for Medical Education and Research. 2006-06-14. Retrieved 2006-11-17.
  7. Sendecka M, Baryluk A, Polz-Dacewicz M (2004). "Prevalence and risk factors of dry eye syndrome". Przegl Epidemiol. 58 (1): 227–33. PMID 15218664.
  8. Kaiserman I, Kaiserman N, Nakar S, Vinker S (2005). "Dry eye in diabetic patients". Am J Ophthalmol. 139 (3): 498–503. PMID 15767060.
  9. Li H, Pang G, Xu Z (2004). "Tear film function of patients with type 2 diabetes". Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 26 (6): 682–6. PMID 15663232.
  10. A. Peral, G. Carracedo, M.C. Acosta, J. Gallar, J. Pintor."Increasing Levels of Diadenosine Polyphosphates in Dry Eye" (2006)Invest.Ophthalmol. Vis. Sci.47 (9):4053–4058 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed]
  11. 11.0 11.1 Miljanović B, Trivedi K, Dana M, Gilbard J, Buring J, Schaumberg D (2005). "Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women". Am J Clin Nutr. 82 (4): 887–93. PMID 16210721.
  12. Tatlipinar S, Akpek E (2005). "Topical cyclosporine in the treatment of ocular surface disorders". Br J Ophthalmol. 89 (10): 1363–7. PMID 16170133.
  13. 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. PMID 16102833.
  14. Micromedex® Healthcare Series, (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://0-www.thomsonhc.com.library.uchsc.edu:80 (cited: 09/05/06).
  15. Barber LD, Pflugfelder SC, Tauber J, Foulks GN. Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Ophthalmology. 2005 Oct;112(10):1790-4.
  16. "Sun Pharma Product List". Sun Pharma. Retrieved 2006-11-27. External link in |publisher= (help)
  17. "Dry eye syndrome". Health encyclopaedia. NHS Direct. 2006-04-10. Retrieved 2007-02-26. External link in |work= (help)
  18. 18.0 18.1 18.2 18.3 "Dry eyes syndrome". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. 2006-10-04. Retrieved 2006-11-16.

Further reading

  • The Dry Eye: A Practical Approach, by Sudi Patel, Kenny Blades, 2003, Butterworth-Heinemann, ISBN 0-7506-4978-X
  • Dry Eye Disease: The Clinician's Guide to Diagnosis And Treatment, by Penny A. Asbell, Michael A. Lemp, 2006, Thieme Medical Publishers, ISBN 1-58890-412-1
  • The Dry Eye Remedy: The Complete Guide to Restoring the Health and Beauty of Your Eyes, by Robert Latkany, 2007, Hatherleigh Press, ISBN 1-57826-242-9

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