Keratitis sicca, or keratoconjunctivitis sicca (dry eye syndrome), is a relatively common inflammatory condition characterized by inadequate tear film protection of the cornea. There are multiple causes that produce either inadequate tear production or abnormal tear film constitution, resulting in excessively fast evaporation or premature destruction of the tear film.
There is no racial predilection for keratitis sicca; however, a female preponderance appears to exist. Sjögren syndrome (a triad of dry eye, dry mouth, and autoimmune connective-tissue disorder) is significantly more common in women (9:1), and milder forms of keratitis sicca also are more common in females than in males.
Regular dental examinations are important because dry mouth, a component of Sjögren syndrome, significantly increases the risk of dental problems, and women should receive regular checkups from their gynecologists.
Patients with Sjögren syndrome can obtain up-to-date information from the following organization:
Sjögren’s Syndrome Foundation
6707 Democracy Boulevard
Suite 325
Bethesda, MD 20817
Phone: (301) 530-4420 or (800) 475-6473
Fax: (301) 530-4415
For patient education information, see Eye and Vision Center, as well as Dry Eye Syndrome, Pink Eye, and Sjögren's Syndrome.
See also the following:
The tear film is constituted by 3 layers, as follows: (1) a lipid layer (0.11 µm thick), produced by the Meibomian glands of the upper and lower lid margin; (2) an aqueous layer (7.0 µm thick), produced by the main and accessory lacrimal glands of Krause and Wolfring; and (3) a hydrophilic mucin layer (0.02-0.05 µm thick), produced by the conjunctival goblet cells. Any abnormality of 1 of the 3 layers produces an unstable tear film and symptoms of keratitis sicca.
A tear layer frequently affected is the aqueous layer, resulting in aqueous tear deficiency (ATD) or lacrimal hyposecretion. A classification scheme stratifies patients with dry eye into those with aqueous tear deficiency and those with increased evaporative loss.
Patients with keratitis sicca have elevated levels of tear nerve growth factor (NGF); these levels were decreased with 0.1% prednisolone.[1] Data suggest that ocular surface nerve growth factor may play an important role in ocular surface inflammation processes associated with dry eyes.
The causes for keratitis sicca are multiple and can be multifactorial. They can be classified into 3 categories by the element of the tear layer that is mostly affected, as follows: (1) those affecting the aqueous tear layer, (2) those affecting the lipid tear layer, and (3) those affecting the mucin tear layer.
The most common disorders associated with abnormalities of the lipid tear layer are blepharitis and rosacea. The severity of the dry eye symptoms appears to correlate to lipid layer thickness. It is now generally recognized that increased evaporation due to a compromised lipid layer is one of the most common etiologies for hyperosmolarity of the tear film.[2]
Idiopathic disease, congenital alacrima, and systemic vitamin A deficiency (xerophthalmia) are the most common conditions associated with aqueous tear deficiency.
Other etiologies include the following:
The following are the most common conditions resulting in abnormalities of the mucin tear layer:
The prognosis with keratitis sicca varies with the severity of the condition. Most patients have mild-to-moderate cases, and they can be treated symptomatically with lubricants, providing good relief of symptoms.
Patients with Sjögren syndrome or prolonged untreated dry eye represent a subgroup of patients with a worse prognosis and a more prolonged treatment regimen.
Significant punctate epitheliopathy can lead to corneal erosions, corneal ulceration (both sterile and infected), corneal neovascularization, corneal scarring, corneal thinning, and even corneal perforation.
Depending on the severity of keratitis sicca, the following are the most common patient complaints:
Documenting the history of exacerbating or alleviating factors and a systemic past medical history is important, including a history of connective tissue disease, thyroid disease, and rheumatoid arthritis.
A review of systems focused on rheumatologic disease; history of neoplasias; and gastrointestinal and ear, nose, and throat (ENT) symptoms should be documented. In addition, ask about a history of dry mouth and request a list of systemic and topical medications the patient is using.
Before placing any drops in the eye of a patient suspected with keratitis sicca, perform an external and slit lamp examination.
A slit-lamp examination may document some of the following important findings:
Determine tear breakup time after placing a drop of fluorescein in the cul-de-sac.
Use rose Bengal staining to look for conjunctival and corneal staining, particularly at the nasal and temporal limbus and/or inferior paracentral cornea.
Perform the 5-minute Schirmer test with and without anesthesia using a Whatman #41 filter paper that is 5 mm in width × 35 mm in length. (Wetting < 5 mm with anesthesia and < 10 mm without anesthesia are considered abnormal.)
Measure reflex secretion with a Schirmer II test if the initial Schirmer test is abnormal. The Schirmer II test is performed by irritating the nasal mucosa with a cotton-tipped applicator before measuring tear production with a Whatman #41 filter paper. (Wetting < 15 mm after 5 min is considered abnormal.)
Sjögren syndrome is characterized by the combination of aqueous tear deficiency and dry mouth (xerostomia). Women comprise 90-95% of patients with this syndrome that has been classified into 3 different subsets, as follows:
All cases of Sjögren syndrome are characterized by a progressive lymphocytic (predominantly B and CD4 lymphocytes) infiltration of the lacrimal and salivary glands that leads to disorganization of the normal gland architecture and consequent loss of function. At this time, the most comprehensive criteria for a diagnosis of Sjögren syndrome include the following:
The following are autoimmune disorders associated with Sjögren syndrome:
Keratitis sicca is generally diagnosed on slit lamp examination. Laboratory testing, such as tear protein analysis and lactoferrin analysis, is also another good metric to help with the diagnosis.
Tear protein analysis allows the measurement of the lysozyme content of tears. Lysozyme accounts for approximately 20-40% of total tear protein content. The main disadvantages of this test include its lack of specificity in cases of meibomitis, herpes simplex keratitis, and bacterial conjunctivitis.
Lactoferrin has antibacterial and antioxidant functions. Lactoferrin analysis is commercially available through colorimetric solid phase and enzyme-linked immunosorbent assay (ELISA) technique. This study offers good correlation with other tests.
Osmolarity analysis, the measure of the salt content of the tear, is another commercially available measurement. This test is performed in a matter of seconds and can help give diagnostic information.
Pathologic examination of the lacrimal gland in patients with keratitis sicca reveals age-related changes, including lobular and diffuse fibrosis and atrophy, as well as periductal fibrosis. An underlying autoimmune mechanism (represented by round cell infiltration) may be present. No circulating autoantibodies are present in patients who do not have Sjögren syndrome with keratitis sicca.
In advanced cases of keratitis sicca, the epithelium undergoes pathologic changes, resulting in squamous metaplasia and loss of goblet cells.
When the mucin layer of the tear is decreased (such as that associated with xerophthalmia or ocular cicatricial pemphigoid), squamous metaplasia and the following cytologic characteristics occur:
Impression cytology is highly sensitive; its main difficulty is the need for proper staining and expert microscopic evaluation of samples.
Early detection and aggressive treatment of keratitis sicca may help avoid corneal ulcers and scarring. The frequency of follow-up care depends on the severity of the signs and symptoms.
Although, supplemental lubrication is the mainstay of treatment for mild and moderate aqueous deficient keratitis sicca, the treatment of any concominant lid disease needs to be addressed. Moreover, the use of topical cyclosporine A has been shown to increase the production of aqueous, as well as increase goblet cell density. Other forms of treatment include the use of silicone plugs that block the puncta (the hole that drains the tears on the lid).
Insert temporary punctal occlusion with collagen (dissolvable) or silicone (permanent) plugs, and, if they are effective, perform electric cauterization of the puncti.
The use of oral omega 3s has beneficial anti-inflammatory properties that aid in the production of tears.
Environment-related issues that may exacerbate the dry eye should be discussed and alternatives may be needed.
Treatment of very severe keratitis sicca or keratitis sicca associated with a connective-tissue disorder, including Sjögren syndrome, should be coordinated with an internist or a rheumatologist.
If mucous strands or filaments are present, remove with forceps and administer 10% acetylcysteine 4 times a day. The surgical treatment of keratitis sicca is reserved for very severe cases in which ulceration or impending perforation of the sterile corneal ulcer occurs.
Lubricating supplements are the most common medications used to treat keratoconjunctivitis sicca. If these agents are to be used more frequently than every 3 hours, preservative-free formulations are the treatment of choice. If a patient has Sjögren syndrome, the use of systemic immunosuppressants should be considered.
Prescribe artificial tears, preferably preservative-free artificial tears, and a lubricating ointment. Mild keratitis sicca cases can be treated with drops 4 times a day. More severe cases require more aggressive treatment, such as drops 10-12 times a day. Thick artificial tear drops or gels can also be used in more severe cases, although these agents tend to blur the vision. Tear ointments can be used during the day, but they are generally reserved to bedtime use because of the poor vision after placement.
Patch with lubrication at night.
Place an artificial tear insert (eg, Lacrisert) into the inferior cul-de-sac every morning.
Surgical care includes the following:
The use of topical cyclosporine A (tCSA) 0.05% ophthalmic emulsion (Restasis) to treat keratoconjunctivitis sicca has proven to be an effective treatment for keratitis sicca.[5, 6]
Clinical Context: Artificial tears lubricate and relieve dry eyes and eye irritation associated with deficient tear production.
Clinical Context: Hydroxypropyl stabilizes and thickens precorneal tear film and prolongs tear film breakup time, which occurs with dry eye states.
Lubricating drops are used to reduce morbidity and to prevent complications. Lubricating ointments prevent complications from dry eyes. Ocular inserts reduce symptoms resulting from moderate to severe dry eye syndromes.
Clinical Context: Ten percent N-acetylcysteine drops are used as a mucolytic agent that can be administered successfully in patients with corneal filaments secondary to extreme keratitis sicca.
Mucolytic agents lower mucous viscosity by digesting mucoproteins. These agents are used when mucous discharge or plaques are present.
Clinical Context: Cyclosporine ophthalmic acts as a partial immunomodulator. It is used to relieve dry eyes caused by suppressed tear production secondary to ocular inflammation.