Etiology of Keratoconjunctivitis Sicca
The conjunctival and corneal surface epithelial cells need to be hydrated. If there is interruption of a continuous, unbroken layer of tears over the exposed surface, desiccation of surface cells leads to tissue damage and inflammation.
There are 2 main types:
Aqueous tear-deficient keratoconjunctivitis sicca is caused by insufficient coverage of the ocular surface by tears due to inadequate tear volume.
Evaporative keratoconjunctivitis sicca (more common) is caused by insufficient coverage of the ocular surface by tears due to accelerated tear evaporation resulting from poor tear quality.
Aqueous tear-deficient keratoconjunctivitis sicca is most commonly an isolated idiopathic condition in postmenopausal women. It is also commonly part of Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more , rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more (RA), or systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more (SLE or lupus). Less commonly, it is secondary to other conditions that scar the lacrimal ducts (eg, cicatricial pemphigoid Ocular Mucous Membrane Pemphigoid Ocular mucous membrane pemphigoid is a chronic, bilateral, progressive scarring and shrinkage of the conjunctiva with opacification of the cornea. Early symptoms are hyperemia and irritation... read more , Stevens-Johnson syndrome Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous hypersensitivity reactions. Drugs, especially sulfa drugs, antiseizure drugs, and antibiotics, are the most common... read more , and trachoma Trachoma Trachoma is a chronic conjunctivitis caused by Chlamydia trachomatis and is characterized by progressive exacerbations and remissions. It is the leading cause of preventable blindness... read more ). It may result from a damaged or malfunctioning lacrimal gland due to graft-vs-host disease, HIV Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more (diffuse infiltrative lymphocytosis syndrome), local radiation therapy, or familial dysautonomia.
Evaporative keratoconjunctivitis sicca is caused by loss of the tear film due to abnormally rapid evaporation caused by an inadequate oil layer on the surface of the aqueous layer of tears. Symptoms may result from abnormal oil quality (ie, meibomian gland dysfunction) or a degraded normal oil layer (ie, seborrheic blepharitis). Patients frequently have acne rosacea Rosacea Rosacea is a chronic inflammatory disorder characterized by facial flushing, telangiectasias, erythema, papules, pustules, and, in severe cases, rhinophyma. Diagnosis is based on the characteristic... read more .
Drying can also result from exposure due to inadequate eye closure at night (nocturnal lagophthalmos or Bell or facial nerve palsy Facial Nerve Palsy Facial nerve (7th cranial nerve) palsy is often idiopathic (formerly called Bell palsy). Idiopathic facial nerve palsy is sudden, unilateral peripheral facial nerve palsy. Symptoms of facial... read more ) or from inadequate frequency of reapplication of tears to the cornea due to an insufficient blink rate (eg, in Parkinson disease Parkinson Disease Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more ).
Systemic drugs can cause or aggravate dry eyes. Different classes of drugs contribute to different types of dry eye, as in the following examples:
Aqueous tear-deficient dry eyes: Diuretics, anticholinergics, antidepressants, beta-blockers, decongestants, oral contraceptives
Evaporative dry eyes: Isotretinoin, antiandrogens
Dry eyes due to poor eyelid closure: Major antipsychotics, adrenergic agonists, botulinum toxin injections
Symptoms and Signs of Keratoconjunctivitis Sicca
Patients report itching; burning; a gritty, pulling, or foreign body sensation; or photosensitivity. A sharp stabbing pain, eye strain or fatigue, and blurred vision may also occur. Some patients note a flood of tears after severe irritation. Typically, symptoms fluctuate in intensity and are intermittent. Certain factors can worsen symptoms:
Prolonged visual efforts (eg, reading, working on the computer, driving, watching television)
Local environments that are dry, windy, dusty, or smoky
Certain systemic drugs, including isotretinoin, sedatives (eg, that have anticholinergic effects), diuretics, beta-blockers, oral contraceptives, and all anticholinergics (including antihistamines and many gastrointestinal drugs)
Symptoms lessen on cool, rainy, or foggy days or in other high-humidity environments, such as in the shower. Recurrent and prolonged blurring and frequent intense irritation can impair daily function. However, permanent impairment of vision is rare.
With both types, the conjunctiva is hyperemic, and there is often scattered, fine, punctate loss of corneal epithelium (superficial punctate keratitis Superficial Punctate Keratitis Superficial punctate keratitis is corneal inflammation of diverse causes characterized by scattered, fine, punctate corneal epithelial loss or damage. Symptoms are redness, lacrimation, photophobia... read more ), conjunctival epithelium, or both. When the condition is severe, the involved areas, mainly between the eyelids (the intrapalpebral or exposure zone), stain with fluorescein. Patients often blink at an accelerated rate because of irritation. With both types, blinking spreads more tears on the ocular surface, reducing or preventing dryness and symptoms. Frequent blinking is thus often a learned compensatory mechanism.
With the aqueous tear-deficient type, the conjunctiva can appear dry and lusterless with redundant folds. With the evaporative type, abundant tears may be present as well as foam at the eyelid margin. Very rarely, severe, advanced, chronic drying leads to significant vision loss due to keratinization of the ocular surface or loss of corneal epithelium, leading to sequelae such as scarring, neovascularization, infections, ulceration, and perforation.
Diagnosis of Keratoconjunctivitis Sicca
Schirmer test and tear breakup test (TBUT)
Diagnosis is based on characteristic symptoms and clinical appearance. The Schirmer test and tear breakup time (TBUT) may differentiate type. Both tests are done before instilling drops of any kind.
The Schirmer test determines whether tear production is normal. After blotting the closed eye to remove excess tears, a strip of filter paper is placed, without topical anesthesia, at the junction of the middle and lateral third of the lower eyelid. If < 5.5 mm of wetting occurs after 5 minutes on 2 successive occasions, the patient has aqueous tear-deficient keratoconjunctivitis sicca. With evaporative keratoconjunctivitis sicca, the Schirmer test is usually normal.
To determine the tear breakup time, the tear film is first made visible under cobalt blue light at the slit lamp Slit-lamp examination The eye can be examined with routine equipment, including a standard ophthalmoscope; thorough examination requires special equipment and evaluation by an ophthalmologist. History includes location... read more by instillation of a small volume of highly concentrated fluorescein (made by wetting a fluorescein strip with saline and shaking the strip to remove any excess moisture). Blinking several times reapplies a complete tear film. The patient then stares, and the length of time until the first dry spot develops is determined (TBUT). An accelerated rate of intact tear film breakup (< 10 seconds) is characteristic of evaporative keratoconjunctivitis sicca.
If aqueous tear-deficient keratoconjunctivitis sicca is diagnosed, Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more should be suspected, especially if xerostomia Xerostomia Xerostomia is dry mouth caused by reduced or absent flow of saliva. This condition can result in discomfort, interfere with speech and swallowing, make wearing dentures difficult, cause halitosis... read more is also present. Serologic tests and labial salivary gland biopsy are used for diagnosis. Patients with primary or secondary Sjögren syndrome are at increased risk of several serious diseases (eg, primary biliary cholangitis Primary Biliary Cholangitis (PBC) Primary biliary cholangitis (PBC; formerly known as primary biliary cirrhosis) is an autoimmune liver disorder characterized by the progressive destruction of intrahepatic bile ducts, leading... read more , non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the... read more ). Therefore, proper evaluation and monitoring are essential.
Several newer tests are being developed to help diagnose keratoconjunctivitis sicca. These include instruments for imaging the eyelid oil glands and measuring the quality of the tear lipid layer and tear osmolarity. Results can vary (eg, from day to day) and may correlate poorly with clinical findings. Also, an office test for ocular surface inflammation (that measures the increased matrix metalloproteinase-9 in tears) is now available. The clinical application of these tests is still uncertain.
Treatment of Keratoconjunctivitis Sicca
Sometimes occlusion of nasolacrimal punctum or tarsorrhaphy
Frequent use of artificial tears can be effective for both types. Low-viscosity artificial tears are useful for replacing volume in aqueous tear-deficient keratoconjunctivitis sicca. More viscous artificial tears coat the ocular surface longer, and artificial tears that contain polar lipids, such as glycerin or nonpolar lipids (eg, mineral oil), reduce evaporation; both types of artificial tears—viscous and lipid—are particularly useful in evaporative keratoconjunctivitis sicca. Artificial tear ointments applied before sleep are particularly useful when patients have nocturnal lagophthalmos or irritation on waking. Most cases are treated adequately throughout the patient’s life with such supplementation.
Staying hydrated, using humidifiers, and avoiding dry, drafty environments can often help. Not smoking and avoiding secondary smoke are important. Most evidence shows that neither diet nor supplements, such as omega-3 fatty acid, improve dry eye disease.
In recalcitrant cases, occlusion of the nasolacrimal punctum may be indicated. In severe cases, a partial tarsorrhaphy can reduce tear loss through evaporation.
Natural tear volume can be augmented by a device that uses soft-tip probes placed into the nose several times a day to apply electrical impulses to stimulate tear production or by applying a nasal spray twice a day that contains a highly selective cholinergic agonist that binds to cholinergic receptors with high affinity, activating the trigeminal parasympathetic pathway to stimulate tear production.
Cyclosporine and lifitegrast drops that decrease the inflammation associated with dryness of the eye are available. They can lead to meaningful improvement in a fraction of patients of both types. These drops sting and may take months before an effect is noticed.
Patients with evaporative keratoconjunctivitis sicca often benefit from treatment of concomitant blepharitis Blepharitis Blepharitis is inflammation of the eyelid margins that may be acute or chronic. Symptoms and signs include itching and burning of the eyelid margins with redness and edema. Diagnosis is by history... read more and associated acne rosacea Rosacea Rosacea is a chronic inflammatory disorder characterized by facial flushing, telangiectasias, erythema, papules, pustules, and, in severe cases, rhinophyma. Diagnosis is based on the characteristic... read more with measures such as the following:
For blepharitis with meibomian gland dysfunction: Gel-filled microwavable warm compresses applied for 10 to 15 minutes 1 to 2 times a week, infrared or automated heating and massaging devices, and/or systemic doxycycline 50 to 100 mg orally once or twice daily (contraindicated in pregnant or nursing patients) to help increase oil flow onto the eye surface and increase the amount and effectiveness of lipids in the tear film, thereby decreasing tear evaporation
For seborrheic blepharitis: Eyelid margin scrubs and/or intermittent topical eyelid antibiotic ointments (eg, bacitracin at bedtime)
Because of the variability of symptoms, validated questionnaires can help monitor response to therapy.
Keratoconjunctivitis sicca is chronic, bilateral desiccation of the conjunctiva and cornea caused by too little tear production or accelerated tear evaporation.
Typical symptoms include intermittent itching; burning; blurring, a gritty, pulling, or foreign body sensation; and photosensitivity.
Findings include conjunctival hyperemia and often scattered, fine, punctate loss of corneal epithelium (superficial punctate keratitis) and conjunctival epithelium.
The Schirmer test and tear breakup test may help determine whether the cause is deficient tear production or accelerated tear evaporation.
Using artificial tears and avoiding corneal drying are usually sufficient treatment, but sometimes occlusion of the nasolacrimal punctum or partial tarsorrhaphy is indicated.
Treatment of concomitant blepharitis is often beneficial.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Absorica, Absorica LD, Accutane, Amnesteem , Claravis , MYORISAN, Sotret, ZENATANE|
|AK-Fluor, Bio Glo, Fluorescite, Fluorets , Fluor-I-Strip, Fluor-I-Strip A.T., Ful-Glo, Ophthalmicflur|
|Advanced Eye Relief, Akwa Tears, Akwa Tears Renewed, Alcon Tears, Artificial Tears, Bion Tears, Blink Tears, Clear eyes, Clear eyes Advance Dry and Itchy Relief, Clear eyes Outdoor Dry Eye Protection, Eye Lubricant , FreshKote, Gen Teal Moderate to Severe, GenTeal , GenTeal Mild, GenTeal Moderate, GenTeal PF, GenTeal Severe, GenTeal Tears Mild, GenTeal Tears Severe Dry Eye, Gonak, Goniosoft, Hypo Tears , Isopto Tears, LiquiTears, LubriFresh P.M., Moisture Eyes, Moisture Eyes Preservative Free, Murine, Natural Balance Tears, Nature's Tears, Opti-Free, Puralube Tears, Refresh, Refresh Celluvisc, Refresh Endura, Refresh Lacri-Lube, Refresh Liquigel, Soothe Lubricant Dry Eye Therapy, Systane, Systane Balance, Systane Complete, Systane Ultra, Teargen, Tears Naturale Forte, Tears Naturale Free, Tears Naturale II, Tears Renewed , TheraTears, Visine Dry Eye Relief, Visine Maximum Redness Relief, Visine Pure Tears, Visine Tears, Visine Tired Eye Relief, Viva|
|Colace Glycerin, Fleet, Fleet Pedia-Lax, HydroGel, Introl , Lubrin, Orajel Dry Mouth, Osmoglyn, Sani-Supp|
|Fleet, Kondremul, Liqui-Doss, Muri-Lube|
|Cequa, Gengraf , Neoral, Restasis, Sandimmune, SangCya, Verkazia|
|Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs|
|AK-Tracin, Baciguent, BaciiM, Baci-Rx, Ocu-Tracin|