A new tool for managing ocular surface disease

Ocular surface disease (OSD)-including such clinical entities as anterior blepharitis, meibomian gland dysfunction (MGD), and dry eye syndrome-represents one of the most common yet most insufficiently treated disorders in optometric practice. Conservative estimates regarding the prevalence of just dry eye in the U.S. place it at about 15 percent of the population, representing nearly 48 million Americans.¹

Additionally, recent surveys of eyecare practitioners suggest that blepharitis is present in 37 percent to 47 percent of all patients who undergo clinical examination.²

But while we recognize the frequency with which these conditions are seen and understand their significance with regard to patient comfort and visual function, our management options for OSD are woefully lacking. The mainstay of our therapy today consists of artificial tear preparations, surfactant lid cleansers, warm compresses for the eyelids, and the occasional antibiotic solution or ointment-this is the exact same therapy that was in vogue for treating OSD 25 years ago!
 

Next: Bacterial biofilms

Bacterial biofilms

It has long been known that bacteria are a key driving force in the pathogenesis of lid margin disease. Indeed, reports dating back to 1945 document the role of Staphylococcus species in blepharitis.³ Today, we also recognize that bacterial flora contribute to the development and perpetuation of MGD, the primary driving force behind evaporative dry eye.⁴

According to experts, bacteria that attach to tissue surfaces (i.e. the eyelid margins) tend to aggregate in a hydrated polymeric matrix of their own synthesis to form a biofilm.⁵ Biofilms provide safe harbor within which the microbes can multiply, vastly increasing the density of bacterial colonies.

Related: Rx lid cleanser aids MGD, blepharitis

This bacterial overgrowth-even in cases of normally quiescent strains such as Staphylococcus epidermidis-leads to a phenomenon known as quorum-sensing.⁴ Quorum-sensing is in turn responsible for the production of pro-inflammatory mediators, cytokines, and proteases, as well as the attraction of neutrophils.^6,7

Additionally, biofilms impart to the bacteria a greatly increased tolerance to antimicrobial agents. We must be careful not to confuse tolerance with bacterial resistance-while bacteria within a biofilm may survive antibiotic therapy, the strains remain susceptible to the treatment if and when the biofilm is removed.⁸

Bacterial biofilms have been well-documented in association with many chronic infectious and inflammatory disorders, including such diverse conditions as periodontitis, cystic fibrosis, otitis media, atherosclerosis, rhinosinusitis, endocarditis, urinary tract infections, and osteomyelitis.⁹

Biofilms have also been implicated in ocular disorders such as contact lens-induced keratitis and endophthalmitis following intraocular surgery.¹⁰ Studies have shown that strains of bacteria isolated from the ocular surface are up to 10 times more likely to form biofilms than similar bacterial species isolated from facial skin.¹¹ More recently, clinical researchers have speculated that biofilms may be a direct mechanism by which bacteria persist and thrive in cases of chronic blepharitis.¹²

That OSD is inflammatory in nature is not a new concept. Even before the Dry Eye Workshop (DEWS) saw fit to include inflammation in the definition of dry eye, researchers had identified inflammatory biomarkers in patients with this disease, and anti-inflammatory therapies such as cyclosporine had been used with success.^13-15

However, the perception of lid margin biofilm as the perpetrator of OSD is a relatively new idea. But when we consider the nature of these disorders-inflammatory, chronic, progressive, and often recalcitrant to conventional antibiotic therapy-this concept makes perfect sense.

It explains why artificial tears alone generally do not provide lasting relief for these individuals. It also explains why surfactant cleansers are typically ineffective in eradicating blepharitis, and why warm compresses applied to the eyelids most often fail to alleviate chronic meibomian gland obstruction. Addressing the biofilm appears to be a crucial step in overcoming the pathogenesis of OSD.

Next: Microblepharoexfoliation

Microblepharoexfoliation

What options exist then for treating the eyelids and lid margins where bacterial biofilm accumulates and induces chronic disease? Current research suggests that one of the most direct and effective methods for removing biofilm and overcoming chronic bacterial infection is by simple mechanical debridement.¹⁶

A procedure for debridement scaling of the lid margin has in fact been advocated by Donald Korb, OD, FAAO, and Caroline Blackie, OD, PhD, in the management of MGD.¹⁷ Although they speculate that the procedure removes “the accumulated stained cells of the [Line of Marx], in combination with… any accumulated debris along the keratinized eyelid margin,” it is quite likely that this technique is simultaneously stripping away at least a portion of the biofilm.

Related: A different approach to treating demodex blepharitis 

The latest technique for eliminating bacterial biofilm from the eyelids and lid margins has been dubbed microblepharoexfoliation (MBE) by the physician who developed the technology, James Rynerson, MD.

MBE is accomplished by the use of BlephEx, a handheld device similar to an Alger brush that rotates a PVA sponge tip along the eyelid margins at approximately 2,000 revolutions per minute. In order to dissolve accumulated oil and dirt from the eyelid structures and expose the bacterial biofilm, the sponge is pre-soaked in a commercial lid cleanser of the doctor’s choice. 

From a macroscopic point of view, MBE removes fibrinous debris at the base of the lashes, oily scales due to seborrheic blepharitis, cylindrical dandruff associated with Demodex species, and the meibomian plugs which are often inherent in MGD.

At the microscopic level, MBE eradicates the biofilm and associated exotoxins and in doing so also likely reduces the bacterial population to below the quorum-sensing numbers that induce virulence factor production. From a clinical point of view, MBE can be completed in fewer than five minutes per eye, and with the use of a topical anesthetic such as 0.5% tetracaine, it is well tolerated and completely painless.

Next: More on MBE

MBE is also a natural for practices dedicated to the concept of ocular surface wellness. For those physicians who embrace a proactive approach to ocular health, MBE can be likened to the dental model of routine, preventive teeth cleaning. In the same way that periodic cleanings can help to remove dental plaque (which actually represents an oral biofilm) and promote healthy teeth and gums, so too can regular MBE treatments remove lid margin biofilm and promote healthier meibomian glands and ocular surface tissues. Performed at regular intervals and augmented with a home lid-cleansing regimen, the need for more aggressive or complex ocular surface therapies may be significantly reduced. Moreover, the inevitable onset of OSD may be substantially delayed or even averted.

While there are many available therapies for OSD, patients invariably want the “magic bullet” that will alleviate their symptoms while reducing the time, cost, and hassle of conventional treatment options. MBE is one of the first and only physician-implemented ocular surface therapies that provide the type of lasting relief our patients expect and deserve.

Related: Using the SPEED questionnaire to identify dry eye patients

References:

1. Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol. 2014 Apr;157(4):799-806.

2. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf. 2009 Apr;7(2 Suppl):S1-S14.

3. Florey ME, McFarlan AM, Mann I. REPORT OF FORTY-EIGHT CASES OF MARGINAL BLEPHARITIS TREATED WITH PENICILLIN. Br J Ophthalmol. 1945 Jul;29(7):333-8.

4. O'Brien TP. The role of bacteria in blepharitis. Ocul Surf. 2009 Apr;7(2 Suppl):S21-2.

5. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999 May 21;284(5418):1318-22.

6. Kulacoglu DN, Ozbek A, Uslu H, et al. Comparative lid flora in anterior blepharitis. Turk J Med Sci. 2001;31(4):359-63.

7. Schauder S, Bassler BL. The languages of bacteria. Genes Dev. 2001 Jun 15;15(12):1468-80.

8. Bayles KW. The biological role of death and lysis in biofilm development. Nat Rev Microbiol. 2007 Sep;5(9):721-6.

9. Bjarnsholt T. The role of bacterial biofilms in chronic infections. APMIS Suppl. 2013 May;(136):1-51.

10. Zegans ME, Becker HI, Budzik J, O'Toole G. The role of bacterial biofilms in ocular infections. DNA Cell Biol. 2002 May-Jun;21(5-6):415-20.

11. Suzuki T, Kawamura Y, Uno T, et al. Prevalence of Staphylococcus epidermidis strains with biofilm-forming ability in isolates from conjunctiva and facial skin. Am J Ophthalmol. 2005 Nov;140(5):844-850.

12. Abelson MB, McLaughlin J. Of biomes, biofilm and the ocular surface. Rev Ophthalmol. 2012 Sep;19(9):52-4.

13. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007 Apr;5(2):75-92.

14. Stern ME, Gao J, Schwalb TA, et al. Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye. Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2609-14.

15. Stonecipher K, Perry HD, Gross RH, Kerney DL. The impact of topical cyclosporine A emulsion 0.05% on the outcomes of patients with keratoconjunctivitis sicca. Curr Med Res Opin. 2005 Jul;21(7):1057-63.

16. Black CE, Costerton JW. Current concepts regarding the effect of wound microbial ecology and biofilms on wound healing. Surg Clin North Am. 2010 Dec;90(6):1147-60.

17. Korb DR, Blackie CA. Debridement-scaling: a new procedure that increases Meibomian gland function and reduces dry eye symptoms. Cornea. 2013 Dec;32(12):1554-7.