|Keratoconjunctivitis sicca (Dry eye syndrome)|
|Classification and external resources|
Keratoconjunctivitis sicca (KCS), also called dry eye syndrome (DES) or keratitis sicca, 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, and as high as 34% in the elderly. The phrase "keratoconjunctivitis sicca" is Latin, and its translation is "dry [inflammation] of the cornea and conjunctiva".
- 1 Symptoms
- 2 Pathophysiology
- 3 Causes
- 4 Diagnosis
- 5 Treatment
- 5.1 General measures
- 5.2 Environmental control
- 5.3 Rehydration
- 5.4 Medication
- 5.5 Covering the eye
- 5.6 Conserving tears
- 6 Prognosis
- 7 Prevention
- 8 Epidemiology
- 9 Occurrence in animals
- 10 See also
- 11 References
- 12 Further reading
- 13 External links
Typical symptoms of keratoconjunctivitis sicca 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, stingy or 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.
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[medical citation needed] in clinical studies of dry eyes.
Having dry eyes for a while can lead to tiny abrasions on the surface of the eyes. In advanced cases, the epithelium undergoes pathologic changes, namely squamous metaplasia and loss of goblet cells. 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.
Deficient tear production or excessive tear evaporation
Keratoconjunctivitis sicca is usually due to inadequate tear production from lacrimal hyposecretion or to excessive tear evaporation. The aqueous tear layer is affected, resulting in aqueous tear deficiency (ATD). 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. 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. Topical lacritin promotes tearing in rabbit preclinical studies.
Aging is one of the most common causes of dry eyes. This is because tear production decreases with age. 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.
About half of all people who wear contact lenses complain of dry eyes. 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. 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. The connection between this loss in nerve sensitivity and tear production is the subject of current research.
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. The corneal nerves stimulate tear secretion. Dry eyes caused by these procedures usually resolves after several months, but it can be permanent. Persons who are thinking about refractive surgery should consider this.
An eye injury or other problem with the eyes or eyelids, such as bulging eyes or a drooping eyelid can cause keratoconjunctivitis sicca. Disorders of the eyelid can impair the complex blinking motion required to spread tears. 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.
Persons with keratoconjunctivitis sicca have elevated levels of tear nerve growth factor (NGF). It is possible that this ocular surface NGF plays an important role in ocular surface inflammation associated with dry eyes.
Dry eyes can usually be diagnosed by the symptoms alone. Tests can determine both the quantity and the quality of the tears. A slit lamp examination can be performed to diagnose dry eyes and to document any damage to the eye.
A Schirmer's test can measure the amount of moisture bathing the eye. This test is useful for determining the severity of the condition. 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.
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.
A lactoferrin analysis test provides good correlation with other tests.
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.
The Tear Osmolarity Test has been proposed as a test for dry eye disease. 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. TearLab (San Diego, CA) suggests that their Osmolarity System is the first objective and quantitative test for diagnosing and managing dry eye patients and involves a lab-on-a-chip test that requires 50 nl of tears. Others have recently questioned the utility of tear osmolarity in monitoring dry eye 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.
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. Rubbing one's eyes can irritate them further, so should be avoided. Conditions such as blepharitis can often co-exist and paying particular attention to cleaning the eyelids morning and night with mild shampoos and warm compresses can improve both conditions.
Dry, drafty environments and those with smoke and dust should be avoided. 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. Using a humidifier, especially in the winter, can help by adding moisture to the dry indoor air.
For mild and moderate cases, supplemental lubrication is the most important part of treatment.
Application of artificial tears every few hours 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 has demonstrated that this modality is more effective than artificial tears in a randomized control study.
Lubricating tear ointments can be used during the day, but they generally are used at bedtime due to poor vision after application. They contain white petrolatum, mineral oil, and similar lubricants. They serve as a lubricant and an emollient. Application requires pulling down the eyelid and applying a small amount (0.25 in) inside. Depending on the severity of the condition, it may be applied from every hour to just at bedtime. It should never be used with contact lenses. Specially designed glasses that form a moisture chamber around the eye may be used to create additional humidity.
Inflammation occurring in response to tears film hypertonicity can be suppressed by mild topical steroids or with topical immunosuppressants such as Restasis (ciclosporin). Elevated levels of tear NGF can be decreased with 0.1% prednisolone.
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. This finding is consistent with postulated biological mechanisms. Early experimental work on omega-3 has shown promising results when used in a topical application or given orally. 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.
Topical cyclosporin (topical cyclosporin A, tCSA) 0.05% ophthalmic emulsion is an immunosuppressant, marketed in the United States by Allergan under the trade name Restasis. Approved as a prescription product by the U.S. Food and Drug Administration in 2002, the drug decreases surface inflammation. It is thought to work through inhibition of transcription factors required for cytokine production and T-lymphocyte maturation. In a trial involving 1200 people, Restasis increased tear production in 15% of people, compared to 5% with placebo.
Usually, 1 gtt (drop) of Restasis is instilled in each eye twice a day, 12 hours apart. It should not be used while wearing contact lenses, during eye infections or in people with a history of herpes virus infections. Side effects include burning sensation (common), redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision. Long term use of cyclosporin at high doses is associated with an increased risk of cancer<.
Covering the eye
A scleral lens is a large contact lens that rests on the sclera and creates a tear-filled vault over the cornea. In dry eye sufferers this lens bathes the cornea, reducing blurred vision caused by dry eye and providing relief from the dry eye pain caused by the sensitive nerves in that area. The lens also protects the surface of the eye from further damage due to lack of tears, and allows for healing of of the eye surface. Scleral lenses used for dry eye are oxygen permeable, but they cannot be worn overnight and must be sanitized between uses. Pre-manufactured scleral lenses for dry eye patients can be fitted from a set of available lenses by using a trial and error process, which lasts over the course of days, weeks, or months. Newer technology now also allows highly precise custom fitted scleral lenses to be manufactured and milled from scratch after taking a non-invasive 3D digital image of a patient's eye using devices such as an Optical coherence tomography (OCT) scanner. Digital images can also be manipulated to incorporate vision correction and wavefront guided optics, allowing most dry eye patients to achieve some level of vision improvement, with some users achieving 20/15 or better vision. Previously clouding was a periodic complaint of scleral lens wearers, however this problem has been reduced by better fitting techniques and improved supplemental eye drop choices.
Moisture chambers are protective eye wear that partially seal an area around the eye in order to retain moisture. Moisture chambers come in the form of single patches, goggles, glasses, or overnight wraps. Often they are foam lined. Some opaque versions have an insert that can be moistened or warmed and warm overnight. Transparent moisture chambers with good seals often have a foggy appearance due to the moisture trapped inside, so they should not be used for activities such as driving.
There are methods that allow both natural and artificial tears to stay longer.
Blocking tear drainage
In each eye, there are two puncta — little openings that drain tears into the tear ducts. There are methods to partially or completely close the tear ducts. This blocks the flow of tears into the nose, and thus more tears are available to the eyes. Drainage into either one or both puncta in each eye can be blocked.
Punctal plugs are inserted into the puncta to block tear drainage. For people who have not found dry eye relief with drugs, punctal plugs may help. They are reserved for people with moderate or severe dry eye when other medical treatment has not been adequate.
If punctal plugs are effective, thermal or electric cauterization of puncti can be performed. In thermal cauterization, a local anesthetic is used, and then a hot wire is applied. This shrinks the drainage area tissues and causes scarring, which closes the tear duct.
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.
Keratoconjunctivitis sicca usually is a chronic problem. Its prognosis shows considerable variance, depending upon the severity of the condition. Most patients have mild-to-moderate cases, and can be treated symptomatically with lubricants. This provides an adequate relief of symptoms.
When dry eyes symptoms are severe, they can interfere with quality of life. 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.
Keratoconjunctivitis sicca is relatively common within the United States, especially so in older patients. Specifically, the persons most likely to be affected by dry eyes are those aged 40 or older. 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.
While persons with autoimmune diseases have a high likelihood of having dry eyes, most persons with dry eyes do not have an autoimmune disease. 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. This is partly because hormonal changes, such as those that occur in pregnancy, menstruation, and menopause, can decrease tear production.
Racial predilections do not exist for this disease.
Occurrence in animals
Among animals, keratoconjunctivitis sicca occurs in dogs, cats, and horses.
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. 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.
Tear replacers are a mainstay of treatment, preferably containing methylcellulose or carboxymethyl cellulose. 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:
- Cavalier King Charles Spaniel
- Chinese Shar-Pei
- Lhasa Apso
- Shih Tzu
- West Highland White Terrier
- Cocker Spaniel
- Boston Terrier
- Miniature Schnauzer
Keratoconjunctivitis sicca is uncommon in cats. Most cases seem to be caused by chronic conjunctivitis, especially secondary to feline herpesvirus. Diagnosis, symptoms, and treatment are similar to those for dogs.
- "Keratoconjunctivitis, Sicca". eMedicine. WebMD, Inc. January 27, 2010. Retrieved September 3, 2010.
- Schaumberg DA, Sullivan DA, Buring JE, Dana MR (August 2003). "Prevalence of dry eye syndrome among US women". Am J Ophthalmol 136 (2): 318–26. doi:10.1016/S0002-9394(03)00218-6. PMID 12888056.
- Lin PY, Cheng CY, Hsu WM, Tsai SY, Lin MW, Liu JH, Chou P (May 2005). "Association between symptoms and signs of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study". Invest Ophthalmol Vis Sci 46 (5): 1593–. doi:10.1167/iovs.04-0864. PMID 15851556.
- "Keratoconjunctivitis, Sicca". The Merck Veterinary Manual. Merck & Co., Inc. Retrieved 2006-11-18.
- "Keratoconjunctivitis Sicca". The Merck Manual, Home Edition. Merck & Co., Inc. 2003-02-01. Retrieved 2006-11-12.
- "Dry eyes". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. 2006-10-04. Retrieved 2006-11-16.
- Michelle Meadows (May–June 2005). "Dealing with Dry Eye". FDA Consumer Magazine. U.S. Food and Drug Administration. Archived from the original on February 23, 2008.
- "Dry eyes". Mayo Clinic. Mayo Foundation for Medical Education and Research. 2006-06-14. Retrieved 2006-11-17.
- Sendecka M, Baryluk A, Polz-Dacewicz M (2004). "Prevalence and risk factors of dry eye syndrome". Przegl Epidemiol 58 (1): 227–33. PMID 15218664.
- Zhou L, Zhao SZ, Koh SK, Chen L, Vaz C, Tanavde V, Li XR, Beuerman RW (July 2012). "In-depth analysis of the human tear proteome". J Proteomics 75 (13): 3877–85. doi:10.1016/j.jprot.2012.04.053. PMID 22634083.
- Karnati R, Laurie DE, Laurie GW (June 2013). "Lacritin and the tear proteome as natural replacement therapy for dry eye". Exp. Eye Res. 117: 39–52. doi:10.1016/j.exer.2013.05.020. PMID 23769845.
- Samudre SS, Lattanzio FA, Lossen V, Hosseini A, Sheppard JD, McKown RL, Laurie GW, Williams PB (November 2010). "Lacritin, a Novel Human Tear Glycoprotein, Promotes Sustained Basal Tearing and is Well Tolerated". Invest Ophthalmol Vis Sci 52 (9): 6265–70. doi:10.1167/iovs.10-6220. PMC 3176019. PMID 21087963.
- Kaiserman I, Kaiserman N, Nakar S, Vinker S (2005). "Dry eye in diabetic patients". Am J Ophthalmol 139 (3): 498–503. doi:10.1016/j.ajo.2004.10.022. PMID 15767060.
- 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.
- Millodot M (1978). "Effect of long term wear of hard contact lenses on corneal sensitivity". Arch Ophthalmol 96 (7): 1225–7. doi:10.1001/archopht.1978.03910060059011. PMID 666631.
- Macsai MS, Varley GA, Krachmer JH (1990). "Development of keratoconus after contact lens wear. Patient characteristics". Arch Ophthalmol 108 (4): 534–8. doi:10.1001/archopht.1990.01070060082054. PMID 2322155.
- Murphy PJ, Patel S, Marshall J (2001). "The effect of long term daily contact lens wear on corneal sensitivity". Cornea 20 (3): 264–9. doi:10.1097/00003226-200104000-00006. PMID 11322414.
- Mathers WD, Scerra C (2000). "Dry eye; investigators look at syndrome with new model". Ophthalmol Times 25 (7): 1–3.
- 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 
- Tomlinson, A (April 2007). DEWS Report, Ocular Surface April 2007 Vol 5 No 2.
- American Academy of Ophthalmology Cornea/External Disease Panel. 2011 Preferred Practice Pattern® (PPP) guidelines. October 2011.
- Amparo F, Jin Y, Hamrah P, Schaumberg DA, Dana R (September 2013). "What is the Value of Incorporating Tear Osmolarity Measurement in Assessing Patient Response to Therapy in Dry Eye Disease?". Am J Ophthalmol (Epub ahead of print) 157 (1): 69–77.e2. doi:10.1016/j.ajo.2013.07.019. PMID 24060433.
- Lemp MA. (2008). "Management of Dry Eye". American Journal of Managed Care 14 (4): S88–S101. PMID 18452372. Retrieved 2008-07-25.
- Kojima, T.; Higuchi, A.; Goto, E.; Matsumoto, Y.; Dogru, M.; Tsubota, K. (2008). "Autologous Serum Eye Drops for the Treatment of Dry Eye Diseases". Cornea 27: S25–S30. doi:10.1097/ICO.0b013e31817f3a0e. PMID 18813071.
- 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.
- 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.
- MiljanoviÄ‡ 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. PMC 1360504. PMID 16210721.
- Rashid S, Jin Y, Ecoiffier T, Barabino S, Schaumberg M, Dana R D (2008). "Topical Omega-3 and Omega-6 Fatty Acids for Treatment of Dry Eye". Arch Ophthalmol 126 (2): 219–225. doi:10.1001/archophthalmol.2007.61. PMID 18268213.
- Creuzot C, Passemard M, Viau S, Joffre C, Pouliquen P, Elena PP, Bron A, Brignole F (2008). "Improvement of dry eye symptoms with polyunsaturated fatty acids". J Fr Ophthalmol 29 (8): 868–73. PMID 17075501.
- Randomized, double-masked Study to evaluate the effect of supplementation of Omega-3 fatty acids in Meibomian Gland Dysfunction. The study was done by Dr. Andrea Oleñik and Ignacio Jiménez-Alfaro from the Department of Ophthalmology of the Jiménez Díaz Foundation, Madrid, Spain and Ignacio Mahillo from the Department of Statistics, from the same Foundation.
- 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).
- Barber LD, Pflugfelder SC, Tauber J, Foulks GN. Phase III safety evaluation of cyclosporin 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Ophthalmology. 2005 Oct;112(10):1790-4.
- "Restasis" (PDF). Allergan. January 2008. Retrieved 2008-07-23.
- Dantal J, Hourmant M, Cantarovich D, Giral M, Blancho G, Dreno B, Soulillou JP. (1998). "Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens". The Lancet 351 (9103): 623–628. doi:10.1016/S0140-6736(97)08496-1. PMID 9500317. "60 patients developed cancers, 37 in the normal-dose group and 23 in the low-dose group (p<0.034); 66% were skin cancers (26 vs 17; p<0.05). The low-dose regimen was associated with fewer malignant disorders but more frequent rejection."
- "Sun Pharma Product List". Sun Pharma. Archived from the original on 2007-02-13. Retrieved 2006-11-27.
- Gemoules, Gregory. "Wavefront Lens Process – Simplified". LaserFit. Retrieved 13 May 2014.
- Fassbender, Melissa. "Restoring sight with laser fit lenses". Medical Design Technology. Retrieved 1 January 2014.
- Carter, Susan R. (1998). "Eyelid Disorders: Diagnosis and Management". American Academy of Family Physicians. Retrieved 2011-01-07.
- "Dry eyes syndrome". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. 2006-10-04. Retrieved 2006-11-16.
- Ervin AM, Wojciechowski R, Schein O (2010). "Punctal occlusion for dry eye syndrome". Cochrane Database Syst Rev 9: CD006775. doi:10.1002/14651858.CD006775.pub2. PMID 20824852.
- Gelatt, Kirk N. (ed.) (1999). Veterinary Ophthalmology (3rd ed.). Lippincott, Williams & Wilkins. ISBN 0-683-30076-8.
- Maskin, Steven L. (2007-05-28). Reversing Dry Eye Syndrome: Practical Ways to Improve Your Comfort, Vision, and Appearance. Yale University Press. ISBN 978-0-300-12285-5.
- Latkany, Robert (2007-04-03). The Dry Eye Remedy: The Complete Guide to Restoring the Health and Beauty of Your Eyes. Hatherleigh Press. ISBN 978-1-57826-242-7.
- Patel, Sudi; Blades, Kenny (2003-04-10). The Dry Eye: A Practical Approach. Butterworth-Heinemann. ISBN 978-0-7506-4978-0.
- Geerling, Gerd; Brewitt, Horst (June 2008). Surgery for the Dry Eye: Scientific Evidence and Guidelines for the Clinical Management of Dry Eye Associated Ocular Surface Disease. S. Karger AG. ISBN 978-3-8055-8376-3.
- Asbell, Penny A.; Lemp, Michael A. (November 2006). Dry Eye Disease: The Clinician's Guide to Diagnosis And Treatment. Thieme Medical Publishers. ISBN 978-1-58890-412-6.
- Facts About the Cornea and Corneal Disease The National Eye Institute (NEI).
- Dry Eye Syndrome on NHS Choices
- Dry eye pain
- Keratos - European association on ocular surface diseases and lachrymal dysfunctions
- Am.J.Managed Care - Dry Eye Disease: Pathophysiology, Classification, and Diagnosis
- Dry Eye Syndrome on eMedicine
- Dry Eye (Keratoconjunctivitis Sicca) from The Pet Health Library
- Nasolacrimal and Lacrimal Apparatus, The Merck Veterinary Manual