Dry Eyes (Keratoconjunctivitis Sicca)
Dry eye syndrome (DES) is a disorder of the preocular tear film that results in damage to the ocular surface and is associated with symptoms of ocular discomfort. DES is also called keratoconjunctivitis sicca (KCS), keratitis sicca, sicca syndrome, xerophthalmia, dry eye disease (DED), ocular surface disease (OSD), or dysfunctional tear syndrome (DTS), or simply dry eyes. Keratoconjunctivitis sicca is a Latin word 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.” The dry eye syndrome in which the eyes do not produce enough tears is also known as “Sjogren’s syndrome”
Dry eye disease is characterized by instability of the tear film that can be due to insufficient amount of tear production or due to poor quality of tear film, which results in increased evaporation of the tears. Dry eye therefore can mainly be divided into two groups, namely, (1) aqueous production deficient dry eye disease; (2) evaporative dry eye disease.
Hypofunction of the lacrimal glands, causing loss of the aqueous component of tears, may be due to aging, hereditary disorders, systemic disease (eg, Sjögren syndrome), or systemic drugs.
Excessive evaporation of tears may be due to environmental factors (eg, a hot, dry, or windy climate) or abnormalities of the lipid component of the tear film, as in blepharitis.
Mucin deficiency may be due to vitamin A deficiency, or conjunctival scarring from trachoma, Stevens-Johnson syndrome and related conditions, mucous membrane pemphigoid, burns, or topical drugs or their preservatives.
Tear Fluid and Composition
Dry eye is recognized as a consequence of disruption of lachrymal functional unit. The lachrymal functional unit consists of lachrymal glands, ocular surface including cornea, conjunctiva, eyelids, meibomian glands, ocular nerves, and goblet cells.
The tear film is composed of three main layers. The innermost mucin or mucus layer is the thinnest, produced by cells of conjunctiva. The mucus helps the overlying watery layer to spread evenly over the eye. The middle or aqueous layer is the largest, thickest layer produced by the glands of upper lids and the accessory tear glands and contains essentially a very dilute saltwater solution. This layer keeps the eye moist and helps in the removal of any dust, debris, or foreign particles. Defects of this layer cause DES in most cases.
The uppermost layer of tear film is a very thin layer of lipids. These lipids are produced by the meibomian glands and the glands of Zeis (oil glands in the eyelids). This layer helps to decrease evaporation of the watery layer beneath it. The mucous also reduces the surface tension between the lipid layer of the tear film and the water layer, thus contributing to the stability of the tear film.
The tear fluid also consists of complex mixture of proteins, immunoglobulins, mucins, electrolytes, cytokines, lysozymes, lactoferrin, and growth factors. Lysozyme may act synergistically with IgA in lysis of bacteria. Tears also contain lactoferrin, which has some antibacterial effect . Average glucose concentration of the tears is 2.5 mg/dL and average tear urea level is 0.04 mg/dL. Electrolytes such as K, Na, and Cl occur in higher concentration in the tears than in the blood. Osmolarity of tears is 309 mOsm/liter. Average pH of the tears is 7.25 and refractive index of the tear film is 1.336.
Signs and symptoms
The patient complains of dryness, redness, or foreign body sensation. In severe cases, there is persistent marked discomfort, with photophobia, difficulty in moving the lids, and often excessive mucus secretion.
In many cases, inspection reveals no abnormality, but on slit-lamp examination there are subtle abnormalities of tear film stability and reduced volume of the tear film meniscus along the lower lid. In more severe cases, damaged corneal and conjunctival cells stain with the vital stains rose bengal and lissamine green.
In the most severe cases, there is marked conjunctival injection, loss of the normal conjunctival and corneal luster, epithelial keratitis that stains with fluorescein and may progress to frank ulceration, and mucous strands. The Schirmer test, which measures the rate of production of the aqueous component of tears, may be helpful.
Tear Film Breakup Time (TBUT).
The time required for the tear film to break up following a blink is called TBUT. It is a quantitative test for measurement of tear film stability. The normal time for tear film breakup is 15–20 sec. A fluorescein strip is moistened with saline and applied to the inferior cul-de-sac. After several blinks, the tear film is examined using a broad-beam of slit lamp with a blue filter for the appearance of the first dry spots on the cornea. TBUT values of less than 5–10 seconds indicate tear instability and are observed in patients with mild to moderate dry eye disease. TBUT can also be measured without the addition of fluorescein to the tear film and is called noninvasive BUT (NIBUT). It uses a grid or other patterns directed on the precorneal tear film for observation of image distortion and time from opening the eyes to the first sign of image distortion is measured in seconds.
In a staining method, special dyes such as Rose Bengal, lissamine green, and fluorescein are used to determine abnormalities of surface of the eye, quality of tear film, and severity of dryness. It is simple and easy way to recognize the severity of the dryness. Mild cases of DES are detected more easily using Rose Bengal than fluorescein stain and conjunctiva is stained more intensely than the cornea. Staining pattern can be photographed and graded using one of several scoring systems.
Fluorescein pools in epithelial erosions, stains degenerating or dead cells, and stains the cornea more than the conjunctiva. Rose Bengal and lissamine green stain dead, devitalized cells as well as healthy cells with inadequate protection. Lissamine green is preferable to Rose Bengal as it avoids the pain, discomfort, and corneal toxicity that are associated with Rose Bengal. However it is somewhat less sensitive and more transient and thus more difficult to appreciate on slit-lamp examination.
Schirmer test quantitatively measures the tear production by the lacrimal gland during fixed time period. The basic test is performed by instilling topical anaesthetic and then placing a thin strip of filter paper in the inferior cul-de-sac. The patient’s eyes are closed for 5 minutes and the amount of tears that wets the paper is measured in terms of length of wet strip. This Schirmer II test measures tear of lacrimal gland by stimulation of lacrimal reflex arc and wetting of <15 mm after 5 minutes is considered abnormal. The results are variable as any manipulation of the eyelid can alter the results of the test. Further tear drainage can affect the results. Value of less than 6 mm of strip wetting in 5 minutes is accepted as diagnostic marker for aqueous tear deficiency. The Schirmer I test measures both basic and reflex tearing and is performed in a similar way to basic test but without use of a topical anaesthetic
Tear Function Index (TFI).
It is a more specific and sensitive test for quantitative measurement of the tears. It evaluates the tear dynamics of production and drainage and helps detect subjects suffering from dry eye. Its numerical value is obtained by dividing the Schirmer II test value in millimeters by tear clearance rate. The higher the numerical value of TFI, the better the ocular surface. Values below 96 suggest dry eyes. It is also called Liverpool modification
Osmolarity of normal eye is 309– 312 mOsm/L and the value increases with severity of dry eye disease. It gives qualitative information of tear production. It is a very sensitive test but lacks specificity.
The information of etiology of the disease can be obtained from biopsy of conjunctival and lateral lacrimal glands. Impression cytology serves as a minimally invasive alternative to ocular surface biopsy. Progression of ocular surface changes such as marked decrease in goblet cell count and keratinization is monitored by collecting superficial layers and examined microscopically. It is a very sensitive method but requires proper staining and expert microscopic evaluation.
This method is costly and uses the decay of sodium fluorescein for measurement of tear flow and volume. The tear turnover rate, defined as the percentage by which the fluorescein concentration in tears decreases per minute after instillation, is also reduced in patients with symptomatic DES.
Tear Ferning Test (TFT).
The tear ferning test (TFT) can be used to help diagnose the quality of tears/mucin, DES, and hyperosmolarity. A drop of tear fluid is collected from the lower eyelid and then placed onto a microscope slide and allowed to dry by evaporation. Different forms of branching crystallization patterns are observed and classified. The test diagnoses dry eyes on the basis of the ferning patterns
Aqueous deficiency can be treated with various types of artificial tears. The simplest preparations are physiologic (0.9%) or hypo-osmotic (0.45%) solutions of sodium chloride, which can be used as frequently as every half-hour, but in most cases are needed only three or four times a day. More prolonged duration of action can be achieved with drop preparations containing a mucomimetic such as hydroxypropyl methylcellulose (HPMC), carboxymethylcelluose (carmellose), sodium hyaluronate, polyvinyl alcohol, or polyacrylic acid (carbomers), or by using petrolatum ointment or a hydroxypropyl cellulose (Lacrisert) insert.
Autologous serum eye drops may be used in severe cases. All these mucomimetics are particularly indicated when there is mucin deficiency. If there is tenacious mucus, mucolytic agents (eg, acetylcysteine 10% or 20%, one drop six times daily) may be helpful.
Artificial tear preparations are generally very safe and without side effects. However, preservatives included in some preparations to maintain sterility are potentially toxic and allergenic and may cause keratitis and cicatrizing conjunctivitis in frequent users. The development of such reactions may be misinterpreted as a worsening of the dry eye state requiring more frequent use of the artificial tears and leading in turn to further deterioration, rather than being recognized as a need to change to a preservative-free preparation.
Disease modification can be achieved with topical antiinflammatory agents such as lifitegrast 5%, an integrin antagonist; corticosteroids, of which loteprednol (Lotemax) is favored because of its low risk of intraocular adverse effects; or calcineurin inhibitors, of which cyclosporine 0.05% ophthalmic emulsion (Restasis) twice a day has been used most widely. Diquafosol eye drops promote water transfer, rebamipide eye drops increase mucin secretion, and vitamin A is included in some artificial tear preparations. Increased dietary intake of omega-3 fatty acids has been reported to be beneficial.
Lacrimal punctal occlusion by canalicular plugs or cautery is useful in severe cases. Blepharitis is treated as described above. Associated blepharospasm may benefit from botulinum toxin injections.