H16.221-223 Keratoconjunctivitis Sicca

Conjunctival epitheliopathy revealed with lissamine dye

ICD-10 Diagnosis Codes:

H16.221–Keratoconjunctivitis Sicca, right eye
H16.222–Keratoconjunctivitis Sicca, left eye
H16.223–Keratoconjunctivitis Sicca, bilateral

Title
Keratoconjunctivitis Sicca

Category
Keratitis

Description
A disease of the surface of the eye that arises due to either decreased tear film production or increased tear film evaporation.

DEFINITION

The modern model of dry eye syndrome describes a collection of disorders that interfere with the ability of the lacrimal apparatus to maintain a healthy tear film over the ocular surface. The common link between the various disorders is that they all end up with a loss of water from the tear film.

The loss of water from the tear film increases its osmolarity above the normal limit of 311 mOsm/L. The increase in tear film osmolarity is the link between changes in the lacrimal glands, changes in the eyelids, and disease of the ocular surface.

Ocular Surface Anatomy and Physiology

The goal is to keep the cornea clear and healthy
Maintenance of physiology requires harmonization betwen the ocular surface epithelium and the tear film
Normal ocular surface-tear film interaction is controlled by a neural reflex loop that depends upon intact nerve endings at the ocular surface
Maintenance of physiology also requires that secretory and excretory systemsbe intact and functioning
Normal motor function of the eyelids and periorbital musculature is essential for tear film stability

NATURAL HISTORY

Keratoconjunctivitis sicca (dry eye syndrome) evolves through a sequence of four milestones.

Loss of water from the tear film with an increase in tear film osmolarity
Decreased conjunctival goblet cell density and decreased corneal glycogen
Increased corneal epithelial desquamation
Destabilization of the cornea-tear interface

1st Milestone – Loss of water from the tear film with an increase in tear film osmolarity

The tear film is a balanced mixture of water, mucin, lipids, electrolytes, proteins, and immunoglobulins. When water is lost from a balanced tear film, it produces an imbalance that is characterized by an increase in tear film osmolarity. The osmolarity changes when water is lost from the tear film while solutes such as sodium and potassium are not. The first milestone may be accompanied by mild to moderate patient symptoms and no clinical signs. If left untreated, the disease is likely to progress.

2nd Milestone – Decreased conjunctival goblet cell density and decreased corneal glycogen

Conjunctival epithelial cells secrete transmembrane mucins that form the glycocalyx. The glycolcalyx is a glycoprotein (mucin) coating that covers the corneal and conjunctival epithelium. The function of the glycocalyx is to allow the tear film to bond to the surface of the eye. The conjunctiva also contains specialized goblet cells that secrete a gel-forming mucin that floats free in the tear film to help stabilize it after the blink. When tear film osmolarity is chronically elevated, goblet cells become damaged by the high sodium levels associated with high tear film osmolarity.

High tear film osmolarity also produces an osmotic gradient beween the tear film and the ocular surfce. The osmotic graient is an attempt by the tear film to replace some of the water that is being lost. The mechanism of the osmotic gradient pulls water from the conjunctival and corneal cells into the tear film. This pulling action of the gradient produces a type of osmotic shock that damages some of the cells. As the disease progresses, the level of damage increases. Eventually, enough cells are damaged to produce a clinically significant loss of the inter-cellular attachments between some of the conjunctival epithelial cells. As increasing numers of inter-cellular attachments are damaged, conjunctival epithelial cells begin to slough away at an abnormally high rate. This abnormal sloughing of epithelial cells is called conjunctival epithelial desquamation.

Conjunctival Epithelial Desquamation

Abnormal increase in epithelial sloughing results in immature conjunctival epithelial cells moving onto the surface of the eye
Immature cells do not have the surface cell coating of glycoprotein (mucin) needed for tear film bonding
Uncoated cells are subject to an increase in dessication and injury due to poor tear film bonding
Lissamine green dye stains the areas of the conjunctival surface that are not protected by mucin
As the conjunctival desquamation accelerates, the damaged cells release inflammatory mediators onto the surface of the eye and the inflammatory process begins

3rd Milestone – Increased corneal epithelial desquamation

Continued exposure to the osmotic gradient produced by high tear film osmolarity will eventually damage the cornea. The osmotic shock that increases the rate of conjunctival epithelial desquamation eventually increases the rate of corneal epithelial desquamation. The result is also the same – immature corneal epithelial cells reaching the ocular surface without a glycoprotein surface coating.

Corneal Epithelial Desquamation

Abnormal increase in sloughing results in immature corneal epithelial cells moving onto the surface of the eye
Immature cells do not have the surface cell coating of glycoprotein (mucin) needed for tear film bonding
Uncoated cells are subject to an increase in dessication and injury due to poor tear film bonding
Lissamine green dye stains the areas of the corneal surface that are not protected by mucin
As the corneal desquamation accelerates, the damaged cells perpetuate the inflammatory process by releasing additional inflammatory mediators onto the ocular surface

Corneal Epithelial Desquamation

Cornea is not clear and healthy
Corneal epitheliopathy stains with fluorescein dye
Decreased corneal glycogen reduces the amount of energy available for epithelial wound repair and leads to punctate keratopathy
Puntate keratopathyon the central cornea is enhanced with fluorescein dye and cobalt blue filter
Dye staining reveals damaged epithelial cells and/or areas of abnormal epithelial cell sloughing
Interpalpebral location of the dye staining pattern suggests an aqueous deficiency dry eye syndrome
Central corneal location of the dye staining pattern suggests moderate-to-advanced dry eye disease

4th Milestone – Destabilization of the cornea-tear interface

The decrease in corneal glycogen precipitates the last milestone in the natural history of dry eye syndrome – destabilization of the cornea-tear interface secondary to the loss of epithelial microvilli. As changes in the corneal epithelial cell surface become more severe, surface glycoproteins are lost. The lost of these glycoproteins (primarily mucins) degrade the glycocalyx and further destabilize the cornea-tear interface.

Destabilization of the Cornea-Tear Interface

Damaged epithelial cells stain with fluoescein dyeDry spots form overdamaged areas of the corneal epithelium
Geographic areas of abnormal epithelial sloughing stain with fluorescein dye
Fluorescein dye staining indicate areas of the corneal epithelium without microvilli to interface with the tear film
When large areas of the corneal epithelium are damaged or missing, the lack of microvilli to create a cornea-tear interface leads to areas of poor corneal wetting
Areas of poor corneal wetting are indicated by dark spots or streaks (dry spots)visible in the tear film after the blink

DIAGNOSTIC EVALUATION

The main goal of the diagnostic evaluation in a patient with keratoconjunctivitis sicca is to accomplish the following:

To establish the diagnosis of keratoconjunctivitis sicca
To determine WHY there is a loss of water from the tear film
To establish appropriate therapy
To relieve discomfort
To prevent complications
To educate patients and involve them in managing their dry eye disease

To obtain the information required to determine a clinical diagnosis of keratoconjunctivitis iscca and to prescribe a treatment plan, the following service components of a medical eye examination should be performed.

Patient history
General medical observation
Adnexal examination
External ocular examination with biomicroscopy

Patient History

Patients with keratoconjunctivitis sicca may present with any of the following abnormal clinical symptoms:

Dry eyes
Itchy eye
Burning eyes
Scratchy eyes
Stinging eye
Watery eyes
Light sensitivity
Gritty sensations
Eye pain
Blurred vision

In addition to physiological conditions, symptoms can be worsened by exposure to environmental conditions such as wind, air conditioning, and temperature extremes. Activities that reduce blink rate (e.g., extended periods of reading, computer viewing, or driving) can produce more severe symptoms.

External Ocular Examination with Biomicroscopy

Patients with keratoconjunctivitis sicca may present with abnormal clinical signs in any of the following anatomical areas:

Tear film
Eyelid
Conjunctiva
Cornea

		Clinical Appearance of the Tear Film To evaluate the tear film touch a wet fluorescein strip to the patient’s inferior tarsal conjunctiva Lack of spontaneous fluorescence indicates decrease tear film volume Mucous strands in an abnormal tear film stain with fluorescein dye

Clinical Appearance of the Tear Film Loss of water from the tear film results in decreased tear volume Decrease tear volume is associated with debris in the tear film Dehydrated mucus that has precipitated in the inferior fornix indicates a severe loss of water from the tear film

		Clinical Appearance of the Tear Film Rapid development of dark spots in the precorneal tear film after the installation of fluorescein dye Finding is used diagnostically as the tear film breakup time measurement Abnormal tear film breakup time indicates tear film instability Up to 50% of all patient with dry eye syndrome will have normal tear film stability The corneal epithelial changes required to cause tear film instability occur late in the natural history of dry eye syndrome

Clinical Appearance of the Tear Film In patient’s with evaporative dry eye syndrome secondary to posterior blepharitis, the appearance of the tear film has a watery quality Patients may report their eyes feel like they are tearing The tears tend to splash around more on the surface of the eye because the lack of meibum secondary to the blepharitis increases the surface tension of the tear film This sensation occurs because the oil barrier created by the secretion of meibum onto the lid margin is missing As a result, tear fluid can touch the cutaneous portion of the muco-cutaneous junction, making it feel as if the eyes are tearing

		Clinical Appearance of the Eyelid The muco-cutaneous junction is a line of squamous cells that runs along the entire length of the upper and lower eyelid margin This line of demarcation between the palpberal conjunctiva and the outer eyelidis also known as Marx’s line Anterior displacement of Marx’s line is visible with lissamine green staining This clinical finding is associated with blepharitis-induced evaporative dry eye syndrome

Clinical Appearance of the Conjunctiva Conjunctival staining occurs relatively early in the natural history of dry eye syndrome The paternal of conjunctival staining is more useful than the presence or absence of staining In patients with dry eye syndrome, the nasal conjunctiva usually stains more than the temporal conjunctiva

		Clinical Appearance of the Cornea Central corneal staining is a clinical sign of moderately- severe dry eye syndrome This clinical finding occurs late in the natural history of the disease

CLASSIFICATION

According to the 2004 recommendations from the Delphi Panel, dry eye syndrome can also be classified by the stage of the disease.

Severe symptoms
Severe corneal staining
Corneal erosions
Conjunctival scarring

Dry Eye Severity Level		Clinical Signs And Symptoms
Level 1 – Mild		Mild to moderate symptoms No clinical signs Mild to moderate conjunctival signs
Level 2 – Moderate		Moderate to moderately-severe symptoms Tear film abnormalities Mild corneal punctate staining Conjunctival staining Visual blur, glare, photophobia
Level 3 – Moderately-severe		Moderately-severe to severe symptoms Marked corneal punctate staining Central corneal staining Filamentary keratitis
Level 4 – Severe		Severe symptoms Severe corneal staining Corneal erosions Conjunctival scarring

In addition to disease staging, dry eye syndrome can be classified by etiology or clinical appearance.

Etiology of decreased tear film volume

Decreased tear production
Increased tear evaporation

Presence of eyelid margin disease

Presence of clinically apparent inflammation

DIFFERENTIAL DIAGNOSES

This would include other diseases that present with a superficial punctate keratopathy or excess mucus accumulation in the tear film.

		Blepharitis Toxins related to the release of inflammatory mediators can produce superficial punctate keratopathy on the inferior cornea

		Exposure Keratoconjunctivis Poor eyelid closure or an elevated conjunctival mass can produce a superficial punctate keratopathy that is similar in appearance to the damage caused by dry eye syndrome

		Chemical Burn Mild to moderate burns can produce superficial punctate keratopathy or sloughing of the entire epithelium

		Topical Drug Toxicity Any eyedrops with preservatives that are used frequently may produce a superficial punctate keratopathy

		Contact Lens-Induced Superficial Punctate Keratopathy Contact lens overwear, tight lens sydrome, solution toxicity and giant papillary conjunctivitis can produce a superficial punctate keratopathy

		Retained Conjunctival Foreign Body A foreign body under the eyelid can produce linear epithelial defects in a vertical orientation

		Conjunctivitis Mucous discharge associated with bacterial conjunctivitis can mimic the appearance of dehydrated mucous that collects in the inner canthus of dry eye patients

		Trichiasis Misdirected lashes cam produce superficial keratopathy In entropion or ectropion, an eyelid margin turned in or out can mechanically damage the cornea and cause superficial keratopathy

		Trauma Habits such as chronic eye rubbing can mechanically damage the corneal epithelium resulting in superficial punctate keratopathy

TREATMENT OPTIONS

To follow best practices treatment guidelines, use the algorithm developed by Delphi Panel.

Level 1 – Mild Dry Eye Syndrome

Patient counseling
Preserved artificial tears
Environmental management
Allergy eye drops
Increased water intake
Use of hypoallergenic products
If no improvement, add level 2

Level 2 – Moderate Dry Eye Syndrome

Unpreserved artificial tears, gel, ointments
Topical immunomodulators (e.g., Restatis Ophthalmic Emulsion)
Topical steroids
Secretagogues
Nutritional support
If no improvement, add level 3

Level 3 – Moderately-Severe Dry Eye Syndrome

Oral tetracyclines
Punctal occlusion
If no improvement, add level 4

Level 4 – Severe Dry Eye Syndrome

Systemic anti-inflammatory therapy
Oral cyclosporine
Moisture goggles
Acetylcysteine
Punctal cautery
Eyelid surgery

In 2006, the Asclepius Panel enhanced the Delphi Panel’s recommendation for treating dry eye syndrome. Their recommendations was to prescribe steroids in conjunction with Restasis earlier in the natural history of the disease.

Their recommendations include the following treatment guidelines:

Day 1 – initiate treatment with Lotemax eyedrops 4x per day; use artificial tears as needed
Day 14 – reduce Lotemax to twice daily and discontinue over the next 2-4 weeks; begin Restasis twice daily
Day 60 – continue with Restasis twice daily; use Lotemax up to 4x per day for breakthrough period
Day 180 – monitor patient’s progress

REFERENCES

1. Bowling EL. Vital stains in cornea and contact lens practice. Review of Cornea and Contact Lenses. 2005 Jan/Feb: 25-28.
2. Silbert JA. Is it an ulcer or an infiltrate? RevOptom. 2007 June 15; (6): 91-101.
3. Edwards K, Brian G, Stretton S, Stapleton F, Willcox MD, Sankaridurg PR, Sweeney DF, Holden BA. Microbial Keratitis and Silicone Hydrogel Lenses. Contact Lens Spectrum. 2004 Jan: 38-42.
4. Snyder C. Solution Interaction with the Ocular Surface: The Significance in Making the Grade. Clinical & Refractive Optometry. 2005; 16(5): 134-140.
5. Raizman M. Maintaining Corneal Barrier Integrity. 2007 Oct 15; (10): 5-6.
6. Karpecki PM. Much Ado About Staining. RevOptom. 2006 Nov 15; (11): 135-136.

ICD-9 DIAGNOSIS CODES

370.33
Keratoconjunctivitis sicca

ASSOCIATED CPT CODES

92285
External ocular photography

92132
Anterior segment imaging

H16.221-223 Keratoconjunctivitis Sicca

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