Tear film instability can lead to ocular surface damage, keratitis

This is a cycle that can be halted with effective protection of the eye through use of appropriate ophthalmic therapies, one clinician says.

Issue: May 1, 2005

ByJoseph F. Mussoline, MD

Keratitis is a broad term, encompassing inflammation of the cornea due to a multitude of possible causes including, but not limited to, infection of viral, bacterial or fungal origin or irritation due to dryness or mechanical stimuli such as contact lenses. In this article we will focus specifically on keratitis as it relates to dry eye.

In terms of dry eye, clinically evident signs and symptoms can be the result of a variety of causes. Internal insults, such as Sjögren’s syndrome or systemic diseases with an inflammatory element, can induce dry eye as a component of the larger illness. Dry eye has many potential etiologies, from hormonal changes at menopause to neuronal damage, such as that occurring during LASIK. In a similar manner, neurotrophic keratitis, occurring when the trigeminal nerve is damaged or impaired, is another nerve-based cause of ocular surface damage. Such an injury causes reductions in corneal sensitivity, which can become clinically evident as signs of damage on the corneal epithelium.

Ocular protection index

Beyond these physiological causes of dry eye, external insults, such as prolonged exposure of the ocular surface, can also lead to dry eye and the exacerbation of signs and symptoms of damage to ocular surface cells. Ocular surface exposure can become injurious when the tear film is breaking up abnormally quickly and/or the blink rate is not rapid enough to maintain a smooth continuous layer of tear film over the ocular surface. These two measures can be combined and noted as the ocular protection index, which is the tear breakup time divided by the interblink interval. When this value is greater than 1, the spreading of the tear film with each blink occurs before the tear film breaks up, indicating a protected ocular surface.

If this value is less than 1, there is a brief period of time when the tear film has broken but the next blink has not yet occurred. Over the span of a day, month or year, these repeated brief exposures can cumulatively result in damage to the ocular surface. Factors such as prolonged visual tasks or adverse ambient conditions (heat, low humidity and wind) can contribute to the problem and extend these brief exposures by increasing the interval between blinks and/or decreasing tear film breakup time. These external factors can exacerbate an existing dry eye condition such as those evident with systemic disease or nerve damage.

In keratoconjunctivitis sicca (KCS), initially there is a loss of conjunctival goblet cells, which can eventually lead to edema and morphological intracellular changes of the conjunctival epithelial cells, desquamation and changes in conjunctival epithelial cells, such as decreased density and loss of nuclei. Damage is typically evident on the conjunctiva before the cornea, as the cornea seems more resistant to KCS. However, signs can potentially progress to the cornea, resulting in surface cellular damage there as well. This in turn can affect tear film stability, cycling toward ever-worsening dry eye and cellular damage.

Three-step process

Each of these varied means by which damage can be incurred on the cornea has the same result — damage to the corneal epithelium that requires healing. The healing of a corneal wound is a delicate procedure, differing from that of other tissues due to the uniqueness of the cornea and the need to maintain a scar-free, nonvascularized tissue. The process typically involves three steps: the latent phase, cell migration and adhesion, and cell proliferation.

The latent phase is essentially preparation of the wound area for rebuilding procedures to follow: Necrotic tissue is removed, and concentrations of neutrophils, fibronectin and fibrin increase. The cell migration phase involves epithelial cells sliding horizontally across the wound area. Migration of these “sheets” of epithelial cells is facilitated by actin filaments, and through a series of temporary anchors, a monolayer of cells is maneuvered until it is firmly anchored in the target location. Epithelial proliferation occurs under the umbrella or shield of the monolayer that was moved into place during the prior phase. During this phase, the normal thickness of epithelium is regained by tissue regeneration from corneal stem cells.

With the ocular surface damage due to dry eye, we most often see damage less severe than that of some other forms of keratitis or corneal injury, which may require treatment in the form of patching, aggressive use of ointments and lubricants, and/or therapeutic soft contact lenses, as well as antibiotics and NSAIDs. Where tear deficiency is the problem, some important considerations may include addressing any damage that has occurred, preventing further damage and alleviating the symptoms of dryness and discomfort experienced by the patient.

Therapies

There are several palliative therapies currently on the market for dry eye, such as over-the-counter artificial tears. These offer temporary relief of the symptomatic discomfort of dry eye and temporary lubrication. There are pros and cons to each. The less viscous, more liquid ones offer quick moisture and brief symptom relief. The thicker agents, such as ointments, have longer-lasting protection; however, these can be problematic for regular or daytime use because the side effects of such high-viscosity agents include blurring of vision and eyelid caking.

Some over-the-counter agents can offer more than just this temporary relief. For example, Systane (hydroxypropyl-guar, borate, Alcon) works via a pH-driven polymerization mechanism upon instillation in the eye. The HP-guar and borate molecules in this solution crosslink to form a shielding gel-like matrix over the surface of the eye. This matrix protects the surface while healing and helps to prevent further damage, similar to the efforts of the eye itself in the second stage of corneal healing in which a shield of cells is moved over the wounded area.

The only prescription medication currently available for dry eye is Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan). However, there are several other agents to watch for in the near future, including secretagogues (15(S)-HETE, P2Y2) and immunomodulatory/anti-inflammatory agents (pimecrolimus). Restasis is most often used for patients with severe dry eye, although many practitioners have turned to a combination therapy approach; they use an artificial tear concomitantly to alleviate any discomfort with use of the prescription and/or discomfort due to dry eye during the 6-month period before the full efficacy of Restasis may be realized. Research has shown that use of supportive therapy is compatible with Restasis use, although differences exist with various combinations. One study found that the combination of Restasis/Systane performed significantly better in alleviating patients’ symptoms (burning, stinging, grittiness and dryness) than Restasis/Refresh.

We must stay alert to the threat of dry eye. The progressive nature of the disease and the potential of clinically significant damage to conjunctival and corneal epithelium make it an important disease to identify and treat. Tear film instability can lead to ocular surface damage, which in turn perpetuates and exacerbates this instability and eventually leads to keratitis. This is a cycle that can be halted with effective protection of the eye through use of appropriate ophthalmic therapies.

For Your Information:

Joseph F. Mussoline, MD, can be reached at ocljfm@comcast.net.

References:

Ousler GW, Emory TB, Welch D, Abelson MB. Factors that influence the inter-blink interval (IBI) as measured by the ocular protection index (OPI). Invest Ophthalmol Vis Sci. 2002(43):E-abstract 56.
Kenyon KR, Yoo SH, Starck T, Wagoner MD. Corneal epithelial defiects and noninfectious ulcerations. In: Albert, Jakobiec, eds. Principles & Practice of Ophthalmology. Elsevier; 2000:926-943.