Breaking Down CL Epitheliopathies

Practitioners should periodically review contact lens-related epitheliopathies and their treatment options to provide their patients with the best lens wear experience.

By Mile Brujic, O.D., and Crystal Brimer, O.D.

Goal Statement:

This article will offer a review of contact lens-related epitheliopa-thies and provide an outline of their treatment options.

Faculty/Editorial Board:

Mile Brujic, O.D.
Dr. Brujic is a partner of Premier Vision Group, a four-location optometric practice in northwest Ohio. He lectures extensively in the areas of ocular disease management and contact lenses.

Crystal Brimer, O.D.
Dr. Brimer is a graduate of UNC-Chapel Hill and Southern College of Optometry. She has practiced full-scope optometry in Wilmington, N.C. for 12 years and has special interest in contact lenses and dry eye management. She is also the owner of Crystal Vision Services, an ophthalmic equipment and practice management consulting company.

Credit Statement:

This course is COPE-approved for 1 hour of CE credit. COPE ID is 34623-CL. Please check your state licensing board to see if this approval counts toward your CE requirement for relicensure.

Joint-Sponsorship Statement:

This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.

Disclosure Statement:

The authors have no financial relationships to disclose.

While advancements in contact lenses and lens care technology have improved the wear experience, several physiological effects of lens wear continue to contribute to secondary epitheliopathies. There is decreased tear exchange under the lens, which can create a pooling effect of carbon dioxide, debris, antigens and bacteria. The quality of the tear film, especially the mucin layer as it relates to infection, can be negatively affected with a reduction in lipid layer integrity and increased tear evaporation. Changes in the tear film can then have a secondary effect on the functionality of the epithelium.^1-3

In addition to the concerns of conservative and compliant lens wear, many patients are at even higher risk due to external factors, such as overnight wear, protein and lipid build up, hygiene issues, poorly fit lenses, solution hypersensitivity and lid or ocular surface disease.^4,5

In this article, we will explore several epitheliopathies associated with contact lens wear and provide a breakdown of treatment options.

Non-Infectious Infiltrates

Non-infectious infiltrates are an immune-driven response of the cornea to antigens. Corneal insult initiates chemotaxis of leukocytes from the surrounding limbal vasculature into the anterior stroma.⁶

An infiltrate presents as a single (or multiple) round epithelial and sub-epithelial lesion that often does not stain with fluorescein, or may demonstrate late-phase staining. Late-phase staining often appears faintly with poorly demarcated borders several minutes after instillation of fluorescein. When an infiltrate stains, it is essential to pay close attention to its pattern in order to help differentiate it from an infectious ulcer.

The inflammatory cascade and subsequent collection of white blood cells can cause overlying epithelial damage. Because the damage is secondary, the overlying epithelial defect and staining pattern will be smaller than the underlying infiltrate. Typically, there is sectoral injection, only trace cells in the anterior chamber (if any), and just moderate pain and photophobia. Non-infectious infiltrates are small in size (under 2mm) and usually are located toward the peripheral cornea, but may be scattered throughout the entire cornea.⁷

This inflammatory response is well controlled with a steroid.^s And, because any overlying epithelial defect originates from the inflammation, suppressing it with a steroid actually aids the re-epithelialization process.

Using a combination antibiotic/ steroid will protect the compromised cornea from secondary infection. The recommended dosing is q2h while awake for the first one to two days if needed, then q.i.d. until resolution.⁸ Often, practitioners simply will dose the combination agent q.i.d., which seems to resolve most cases.

Infectious Keratitis

Infectious keratitis is a completely different entity that requires meticulous care--both in its diagnosis and treatment. It is the direct result of an infectious organism invading the corneal tissue. A recent study showed that contact lens wearers were 9.31 times more likely to experience microbial keratitis than non-contact lens wearers.⁹

Clinically, bacterial ulcers will usually present as a single, more centrally located infiltrate that stains with fluorescein. They are generally larger in size (greater than 2mm). The staining pattern closely outlines the footprint of the infiltrate because an ulcer originates in the epithelium before penetrating into the stro-ma.¹⁰ There generally is an anterior chamber reaction, stromal edema and significant conjunc-tival hyperemia. Often, there is much more pain associated with an infectious infiltrate than sterile infiltrates, as well as decreased vision and discharge.⁷

Differentiating infectious from non-infectious infiltrates is critical, because the protocol is substantially different between the two treatment regimens (figure 1). Bacterial ulcers are seen at a considerably lower frequency than sterile infiltrates.

1a. Diffuse non-infectious infiltrative keratitis. 1b. Infectious keratitis with significant corneal staining representing the site of bacterial invasion. 1c. Cells in the anterior chamber, which can be seen with an infectious ulcer.

For an infective keratitis, the treatment goal is to eradicate the offending organism and promote corneal healing. This is often done with highly concentrated topical fourth generation fluoro-quinolones.¹¹ Typically, the newer fluoroquinolones—moxifloxacin, gatifloxacin or besifloxacin—are first-line treatments; however, none of these agents currently are approved for use in microbial keratitis.¹²

Depending on the severity of the infection, it is appropriate to initiate treatment at an accelerated frequency over the first several days to rapidly decrease concentrations of offending micoorganisms. Additionally, it is reasonable to incorporate Polytrim (polymyxin b/trimethoprim, Allergan) due to its efficacy against MRSA.

The standard of care for more aggressive or centrally located ulcers is to culture and treat with the appropriate fortified antibiotics. Some doctors prescribe 30-minute dosing intervals in those cases, alternating fluoroqui-nolones with the fortified antibiotics.⁸ However, some research shows equivalent efficacy of fourth-generation fluoroquino-lones to combination fortified antibiotic treatment.¹³

If the ulcer responds well after 48 hours, the drops can often be decreased to q2h until re-epithelialization and then tapered to q.i.d., according to the corneal response. Cycloplegics can help decrease the patient's pain significantly as the infectious infiltrate is healing.

Despite immediate treatment, corneal scarring can threaten the patient's visual outcome, and concurrent steroid treatment has been questioned as a means to minimize the resultant scarring from these infectious events.

A recent, large-scale study established that there was no benefit to the patient's best-corrected visual acuity or resultant scar size when steroids were incorporated into the treatment protocol.¹⁴ However, patients with central ulcers greater than 4mm or those with the worst entering acuities did experience nearly a two-line improvement in visual acuity with adjunctive steroid treatment.

The study also illustrated the safety of concurrent steroid use after 48 hours of fluoroquino-lone treatment in culture positive patients and confirmed that there was no delay in re-epitheliali-zation time in the group using steroids.¹⁴

Advancing Wavelike Epitheliopathy

Advancing wavelike epitheli-opathy is a rare condition that consists of centripetally advancing wavelike epithelium that usually extends from the superior limbus towards the visual axis.¹⁵ The individual's visual acuity may be affected, depending on how far the irregular epithelium extends to the visual axis. This can be seen during standard slit lamp examination, but is significantly easier to identify after the instillation of fluorescein dye while viewing the cornea with a cobalt blue light through a Wrat-ten filter (figure 2). Other signs that may occur include ocular irritation and redness, depending on the severity of the clinical presentation.

2. The appearance of advancing wavelike epitheliopathy while viewing the eye with a cobalt blue light through a wratten filter after the instillation of fluorescein dye.

In vivo confocal microscopy is remarkable for the presence of atypical, elongated and cetripe-tally oriented cells.¹⁶ Additionally, these cells are remarkable for relatively large, hyperreflective nuclei and a loss of visible cellular borders in the basal epithelium.^16,17

The pathophysiology of advancing wavelike epithelium is poorly understood, but is believed to be multifactorial. Risk factors for its development include topical antiglaucoma medications, contact lens solutions, contact lens wear, previous ocular surgery and atopic dermatitis.^15-17

There have been reports in the literature that describe the effectiveness of an application of 1% silver nitrate to the superior limbus.^15-17 Liquid nitrogen also has been documented as an effective treatment for this condition. During the treatment, the corneo-scleral limbus and surface corneal epithelium are exposed to liquid nitrogen through a double freeze-thaw procedure. The technique is to apply liquid nitrogen to the affected area for one to two seconds, wait 30 seconds, and then reapply for another one to two seconds.¹⁸

In 2005, Professors Patrick Caroline and Mark Andre reported on a case in which advancing wavelike epitheliopathy was included in the differential diagnosis. The recommended treatment called for removal of the offending agents while having the patient utilize non-preserved artificial tears.¹⁹

In our office, if visual acuity is not affected, we follow the same treatment plan of removing the suspected offending agent. Initially, we switch contact lens patients who use a multipurpose solution to a hydrogen peroxide system (figure 3). We also look to a daily disposable option, if one is available for their prescription. If the epitheliopathy either is not improving or progressing, it is reasonable to discontinue contact lens wear and have the patient use non-preserved artificial tears. If it continues to progress and/ or visual acuity becomes affected, more extreme measures may be warranted.

3a. A patient using a store brand multipurpose solution presented with advancing wavelike epitheliopathy. 3b. Presentation of the same cornea, three months after switching the patient to a hydrogen peroxide system.

Neovascularization

Corneal neovascularization is a sign of tissue hypoxia. Normally a transparent, avascular structure, the cornea acquires its nutrients from the aqueous, the tear film and the atmosphere. Deeper vas-cularization is also possible and signals a more serious condition. Although the sclera and bulbar conjunctiva are continuous with the cornea, the rich vascular supply that typically nourishes these structures usually abruptly stops at the limbus. Under circumstances of low oxygen, the cornea attempts to acquire more oxygen to nourish itself. This will lead to limbal vasculature signaling and subsequent growth of new blood vessels in a centripetal manner to meet the increased oxygen demands.^20-23

There still doesn't seem to be a true consensus on the amount of oxygen required by the cornea under normal, open-eye conditions. Minimum oxygen permeability requirements range from 24 Dk/t to 90 Dk/t.^24,25 Clinically, most of the contemporary hydro-gel contact lenses utilized in the last two decades seem to avoid significant neovascular changes under daily wear conditions. Concern arises, however, when patients sleep in these lenses for extended periods of time. In the face of such non-compliance, corneal neovascularization is more likely to occur.

High-oxygen permeable contact lenses have alleviated much of the breathability concerns for patients who sleep in their contact lenses. The silicone hydrogel lenses have offered significantly lower rates of corneal neovascu-larization and are an ideal lens option for those sleeping or suspected of sleeping in their lenses. Be cautious because extended wear will increases the risk for other contact lens complications, such as microbial keratitis.^26,27

There are a number of epithelial conditions that can affect our contact lens wearers. Through understanding these conditions and modifying risk factors, along with accurately diagnosing and treating these patients, we can regain healthy corneal physiology and facilitate successful lens wear.

References

1. Villani E, Ceresara G, Beretta S, et al. In vivo confocal microscopy of meibomian glands in contact lens wearers. Invest Ophthalmol Vis Sci. 2011 Jul 13;52(8):5215-9.
2. Alonso-Caneiro D, Iskander DR, Collins MJ. Tear film surface quality with soft contact lenses using dynamic-area high-speed videokeratoscopy. Eye Contact Lens. 2009 Sep;35(5):227-31.
3. Santodomingo-Rubido J, Wolffsohn JS, Gilmartin B. Changes in ocular physiology, tear film characteristics, and symptomatology with 18 months silicone hydrogel contact lens wear. Optom Vis Sci. 2006 Feb;83(2):73-81.
4. Michaud L, Giasson CJ. Overwear of contact lenses: increased severity of clinical signs as a function of protein adsorption. Optom Vis Sci. 2002 Mar;79(3):184-92.
5. Nichols KK, Mitchell GL, Simon KM, et al. Corneal staining in hydrogel lens wearers. Optom Vis Sci. 2002 Jan;79(1):20-30.
6. Baum J, Dabezies OH Jr. Pathogenesis and treatment of "sterile" midperipheral corneal infiltrates associated with soft contact lens use. Cornea. 2000 Nov;19(6):777-81.
7. Stein RM, Clinch TE, Cohen EJ, et al. Infected vs sterile corneal infiltrates in contact lens wearers. Am J Ophthal-mol. 1988 Jun 15;105(6):632-6.
8. Bartlett J, Melton R, Karpecki P, Thomas R. Keratitis: new paradigms in the understanding and management of keratitis. Rev Optom. 2011 Nov;Suppl.
9. Jeng BH, Gritz DC, Kumar AB, et al. Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol. 2010;128(8):1022-8.
10. Melton R, Thomas R. 2011 Clinical guide to ophthalmic drugs. Rev Optom. 2011 May;Suppl.
11. Morlet N, Daniell M. Microbial keratitis: what's the preferred initial therapy? View 2: Empirical fluoroquinolone therapy is sufficient initial treatment. Br J Ophthalmol. 2003 Sep;87(9):1169-72.
12. Scoper SV. Review of third-and fourth-generation fluoroquinolones in ophthalmology: in-vitro and in-vivo efficacy. Adv Ther. 2008 Oct;25(10):979-94.
13. Shah VM, Tandon R, Satpathy G, et al. Randomized clinical study for comparative evaluation of fourth-generation fluoroquinolones with the combination of fortified antibiotics in the treatment of bacterial corneal ulcers. Cornea. 2010;29:751-7.
14. Srinivasan M, Mascarenhas J, Rajamaran R, et al. Corticosteroids for bacterial Keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50.
15. D'Aversa G, Luchs JL, Fox MJ, et al. Advancing wave-like epitheliopathy. Clinical features and treatment. Ophthalmology. 1997 Jun;104(6):962-9.
16. Chiou AG, Kaufman SC, Beuerman R, et al. A confocal microscopic study of advancing wavelike epitheliopathy. Arch Ophthalmol. 1999 Jan;117(1):126-7.
17. Huang Y, Chu HS, Hu FR, et al. Recurrent advancing wavelike epitheliopathy from the opposite side of the initial presentation. Cornea. 2008 Jan;27(1):111-3.
18. Fraunfelder FW. Liquid nitrogen cryotherapy of advancing wavelike epitheliopathy. Cornea. 2006 Feb;25(2):196- 8.
19. Caroline P, André M. Analyzing unilateral complications. CL Spectrum. 2005 Jul. Available at: www.clspec-trum.com/articleviewer.aspx?articleid=12835 (accessed April 2012).
20. Binder PS. The physiologic effects of extended wear soft contact lenses. Ophthalmology. 1980 Aug;87(8):745- 9.
21. Efron N. Vascular response of the cornea to contact lens wear. J Am Optom Assoc. 1987 Oct;58(10):836-46.
22. Van Setten GB, Tervo T, Andersson R, et al. Plasmin and epidermal growth factor in the tear fluid of contact-lens wearers: effect of wearing different types of contact lenses and association with clinical findings. Ophthalmic Res. 1990;22(4):233-40.
23. Mastyugin V, Mosaed S, Bonazzi A, et al. Corneal epithelial VEGF and cytochrome P450 4B1 expression in a rabbit model of closed eye contact lens wear. Curr Eye Res. 2001 Jul;23(1):1-10.
24. Harvitt D, Bonanno J. Re-evaluation of the oxygen diffusion model for predicting minimum contact lens Dk/t values needed to avoid corneal anoxia. Optom Vis Sci. 1999 Oct;76(10):712-9.
25. Ostrem E, Fink B, Hill R. A hypoxic response line model for the human cornea. Br J Optom Disp. 1996;4:53-5.
26. Dart JK, Radford CF, Minassian D, et al. Risk factors for microbial keratitis with contemporary contact lenses: a case control study. Ophthalmology. 2008 Oct;115(10):1647-54.
27. Stapleton F, Keay L, Edwards K, et al. The incidence of contact lens-related microbial keratitis in Australia. Ophthalmology. 2008 Oct;115(10):1655-66.

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