The DEBS Theory of Dry Eye
By: Paul M. Karpecki, OD, FAAO
Clinical Director – PECAA
For many years blepharitis and dry eye disease (DED) were thought to be two completely separate and independent diseases. In this new theory published in Clinical Ophthalmology, the researchers looked at the potential of dry eye being the result of decades of chronic blepharitis.
The Biofilm Bridge
Biofilm is a term we’ve heard a lot about considering most doctors think of overused contact lens cases as a prime example. And although a biofilm can accumulate on an inert structure like a stent or contact lens case 1 , it can also exist on living structures. One prime example is what’s referred to as plaque on one’s teeth, which is essentially biofilm formation 2. The term blepharitis, which by definition means inflammation (ritis) of the eyelids (blepha), lost this component when doctors started equating lid debris or eyelash ‘scurf’ as the key slit lamp finding required to diagnose it. And although there are many forms of blepharitis that show eyelid debris ranging from staphylococcal and seborrheic to demodex, the fact remains that inflammation of the eyelids is enough to be considered blepharitis and the presence of debris, scurf or discharge on the lashes, is not a requirement for a positive diagnosis. What has particularly made the diagnosis of blepharitis and DED difficult in the past is the fact that both of these conditions have significant overlap and hence the theory of causation. As an example, there are multiple overlapping symptoms intertwined within DED 3 ranging from dry, gritty, irritated and itching eyes to tearing and blurred vision. Also both conditions are known to be slowly progressive and chronic having various manifestations depending on the stage of the disease 4. However if a clinician examines the eyelid margins more closely in terms of biofilm formation, this natural bacterial phenomenon may serve as a bridge of understanding between two poorly understood diseases.
Progression of Lid Margin Disease to DED
According to the theory, lid margin disease progresses to inflammation through six steps. These steps are bacterial survival, biofilm formation, over-colonization, quorum-sensing gene activation, virulence factor production and culminates in inflammation that affects the lash follicles, meibomian glands, and lacrimal glands. In step 1, bacteria must first survive the enzymes such as lactoferrin, tear flow, natural cleaning activities of the eyelids with each blink as well the protective mechanism of mucin secreted by goblet cells 5. When a patient’s blink rate decreases due to surgery, extensive digital device use, the use of preservatives such as in glaucoma therapy, systemic medications that decrease tear volume, the presence of various co-morbidities and a whole host of multifactorial contributors, bacteria are able to exist longer. The next step is biofilm formation which has been described as “the prevailing microbial lifestyle” 6&7. Biofilm formation is essentially a survival tactic allowing the bacteria to avoid desiccation and host responses, produce virulence facts and communicate with other bacterial species (aka as quorum-sensing). Adherence of biofilm has been shown in many bacteria but staphylococcus in particular produces a protein known as adhesin, ensuring a tight adherence to the surface 8. It’s not surprising that the lid margin would be a site of adherence since studies have shown that 32 of the isolates cultured from eyes immediately after cataract surgery were positive for having the ability to form biofilms 9. Further-more, although we wash and shower often, it’s rather rare that a person would naturally wash or clean their eyelid margins – particularly the inner eyelid margins, without having been instructed to do so. In fact most people tightly close their eyes when washing their face preventing access to the eyelid margins. This combination leads to the slow progressive, chronic destruction that occurs via inflammation over decades eventually resulting in dry eye and even damage to the lid structure itself.
The four stages of DEBS
According to the theory, there are four stages of progression. Stage 1 DEBS involves the lash follicles where a biofilm can establish itself. This stage can often be assessed under high magnification noting what is termed a ‘volcano sign’ where the base of the lash appears edematous. As it progresses we see ‘scurf’ or sometimes described as cylindrical dandruff in cases of demodex blepharitis, which is a misnomer and likely represents biofilm that has accumulated around the lash that pulled off as the lash slowly grew.
Stage 2 DEBS involves the lash follicles and the meibomian glands (MG) and may also contribute to explaining obvious versus non-obvious MGD as being related to biofilm blocking the large MG orifices (a combination of poor or altered meibum + biofilm) and thus stage 2 DEBS takes longer to achieve. Stage 3 DEBS involves the follicles, MGs and now the accessory lacrimal glands of Krause and Wolfring. The ducts of these lacrimal glands empty along the inside eyelid. The distance, narrow ducts and constant tear flushing serve to protect these glands for decades and thus making them the last glands to be affected by biofilm formation. Stage 4 DEBS occurs when the structural integrity of the eyelid breaks down. Since chronic inflammation eventually affects connective tissue, nerve endings, muscle etc. they can eventually be damaged and lose functionality 10. Examples of this chronic inflammation damage include lid laxity, floppy eyelid syndrome, ectropion and entropion 11.
DEBS theory may help explain any number of factors including how bacteria can survive a Betadine prep prior to surgical procedures resulting in endophthalmitis, for it’s only at the stage of biofilm formation that it can be resistant to an antiseptic 12. Can I prove or disprove this theory? Certainly not but I can state clinically that I have seen an incredible positive impact on my DED patient population when we began treating the biofilm mechanically (e.g. Blephex in office with at home lid scrubs) in addition to anti-inflammatory treatment (topical or systemic) and options for managing the obstructed meibomian glands (Bruder moist hydrating compresses and Lipiflow thermal pulsation). Furthermore, mechanical removal of the biofilm from the lid margin has shown a profound impact on patient’s symptoms, quality of tears and quality of life 13. Since this affects so much of the optometric practice from a pathology perspective but also the fact that contact lens wearers are more prone to early MGD/blepharitis 14&15 and DED 16, we may allow patients to remain in contact lenses longer by consciously focusing on and managing the biofilm component of ocular surface disease. Dentistry has mastered this important aspect of prevention by managing biofilm formation with regular cleanings, brushing and flossing; perhaps it is even more critical in eye care.
1. Artini M, Cellini A, Scoarughi GL, et al. Evaluation of contact lens multipurpose solutions on bac-terial biofilm development. Eye Contact Lens. 2015;41(3):177–182.
2. McSwain BS, Irvine RL, Hausner M, Wilderer PA. Composition and distribution of extracellular polymeric substances in aerobic flocs and granular sludge. Appl Environ Microbiol. 2005;71(2):1051–1057.
3. Bzdrenga J, Daudé D, Rémy B, et al. Biotechnological applications of quorum quenching en-zymes. Chem Biol Interact. Epub 2016 May 22.
4. Ramadhani AM, Derick T, Holland MJ, Burton MJ. Blinding trachoma: systematic review of rates and risk factors for progressive disease. PLoS Negl Trop Dis. 2016;10(8):e0004859.
5. Guzman-Aranguez A, Argüeso P. Structure and biological roles of mucin-type O-glycans at the ocular surface. Ocul Surf. 2010;8(1):8–17.
6. Absalon C, Van Dellen K, Watnick P. A communal bacterial adhesin anchors biofilm and by-stander cells to surfaces. PLoS Pathog. 2011;7(8):e1002210.
7. Pickering BS, Smith DR, Watnick PJ. Glucose-specific enzyme IIA has unique binding partners in the Vibrio cholerae biofilm. MBio. 2012;3(6):e00228-12.
8. Edwards AM, Bowden MG, Brown EL, Laabei M, Masey RC. Staphylococcus aureus extracel-lular adherence protein triggers TNFα release, promoting attachment to endothelial cells via pro-tein A. PLoS One. 2012;7(8):e43046.
9. Kıvanç SA, Kıvanç M, Bayramlar H. Microbiology of corneal wounds after cataract surgery: biofilm formation and antibiotic resistance patterns. J Wound Care. 2016;25(1):12, 14–19.
10. Baudouin C. Ocular surface and external filtration surgery: mutual relationships. Dev Ophthalmol. 2012;50:64–78.
11. Baudouin C, Messmer EM, Aragona P, et al. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction. Br J Ophthalmol. 2016;100(3):300–306.
12. Kıvanç SA, Kıvanç M, Bayramlar H. Microbiology of corneal wounds after cataract surgery: biofilm formation and antibiotic resistance patterns. J Wound Care. 2016;25(1):12, 14–19.
13. Romero JM, Biser SA, Perry HD, et al. Conservative treatment of meibomian gland dysfunc-tion. Eye Contact Lens. 2004;30(1):14–19.
14. Villani E, Ceresara G, Beretta S. In vivo confocal microscopy of meibomian glands in contact lens wearers. Invest Ophthalmol Vis Sci. 2011 Jul 13;52(8):5215-9.
15. Arita R, Fukuoka S, Morishige N. Meibomian Gland Dysfunction and Contact Lens Discomfort. Eye Contact Lens. 2017 Jan;43(1):17-22.
16. Vishnubhatla S, Borchman D, Foulks GN. Contact lenses and the rate of evaporation meas-ured in vitro; the influence of wear, squalene and wax. Cont Lens Anterior Eye. 2012 Dec;35(6):277-81.