Consider biofilm as alternative theory of dry eye etiology
A new theory is that lid margin disease signs and symptoms are due to a biolm.
Eye care professionals know all too well that there have been decades of confusion and complexity surrounding the etiology of dry eye disease. Not only that, but what constitutes dry eye has also been the subject of debate for years. What defines dry eye? How is blepharitis involved? How does aqueous tear deciency, or ATD, relate to meibomian gland dysfunction? Despite our best eorts, our ability to understand the workings of the tear system and how disease affects this system has been limited at best.
A novel theory of dry eye proposed by James Rynerson, MD, and Henry Perry, MD, called “the biolm theory of dry eye disease,” may oer new insights into the etiology of dry eye disease. Biofilm has been shown to be at the center of many disease entities. Rynerson suggests that biolm also plays a central role in dry eye, and once his theory is considered, the complexity of the disease is signicantly lessened.
There are many aspects of dry eye that have contributed to the confusion. The differing presentations of lid margin disease among the young, middle-aged and elderly, as well as the varied nature of symptoms between same-aged patients, instinctively make us consider that differing disease processes are at play. ATD looks different from MGD which looks different from blepharitis. Multiple treatment options exist, including age-old home lid hygiene, all of which have had limited or temporary success. It is natural that a disease that can last nearly an entire lifetime and present differently at different ages would be confusing.
The new theory is that the majority of lid margin disease signs and symptoms are all due to one common etiology, namely a biolm that simply must be present on the lid margin because it is a surface with moisture and nutrients. We as eye clinicians have referred to this biolm for decades by another name, “scurf,” which really has no medical meaning and represents a catch-all term for accumulated debris that does not appear to be part of the normal human skin anatomy. This is analogous to dentists who refer to biolm as “plaque.” But whereas scurf has always been seen as a relatively benign indicator of simple blepharitis, it may actually be the key to understanding virtually all lid margin disease presentations.
The biolm is a product of the bacteria. It is their impenetrable protective fortress against outside detrimental forces, be they environment stresses or host inflammatory responses. The production of the biolm must begin shortly after birth, as soon as the lid margin is colonized with bacterial flora. However, it is proposed that early in life the biolm is typically noninflammatory because a thin early biolm may not be protective of the inhabitants. But as the bacterial population increases in a thicker biolm later in life, their nutrient requirements increase.
Quorum-sensing gene activation (QSGA), discovered at Harvard in 1968 by Dr. John Hastings, only triggers once the population reaches a certain quorum, and this only occurs in a mature biolm. The activated genes now produce highly inflammatory cytolytic toxins and enzymes to liberate nutrients from host surface cells, but the host response has no effect against the bacteria because they are safe within the mature biolm.
The theory therefore suggests that the etiology of lid margin inflammation is quite simple. Biofilm has to be there, a proven process (QSGA) occurs because bacteria have to have nutrients, and the toxins produced to liberate these nutrients cause inflammation.
Once the inflammation occurs, a review of the eyelid anatomy reveals why this disease appears differently at different stages of life. The distinction between clinical presentations is due to two things: size of the lid gland affected and the ease of access into that gland. Rynerson and Perry suggest these stages of disease:
Stage 1. Folliculitis occurs early in life due to the small size of the lash follicle and the relatively easy access by the lid margin surface biolm. This can be seen in the majority of patients by examining the tissue around the base of the eyelash. Any swelling would indicate low-grade inflammation within the lash bulb.
Stage 2. MGD occurs mid-life because the meibomian gland is larger, the route of access is longer and narrower, and the biolm is perhaps impeded somewhat by the constant flow of meibum. Early stage 2 reveals a sudsy meibum due to an enzymatic breakdown of the lipids. Middle stage 2 is simple intraductal obstruction with a thickened mixture of meibum and biofilm, and late stage 2 is frank inflammation of the posterior edge of the lid margin and small domes of the extruded meibum/biolm mixture being held in place by the original surface biolm.
Stage 3. Lacrimalitis occurs late in life due to the distance of the lacrimal gland openings from the surface of the lid margin. This may be a difficult concept to understand how the far distant lacrimal glands could possibly be affected by something on the lid margin until one understands how biofilms propagate. The modalities that may explain this are “rolling, rippling, detachment and dispersal.” Biofilms appear to be nearly unstoppable in the quest for new territory. It is likely that after 50 years, a thin, attenuated layer of biolm manages to access the lacrimals by direct extension along the palpebral conjunctiva. Dispersal of small bits of biolm into the tear film may also contribute to the biofilm’s effect on the lacrimal glands.
The historical thinking has been that ATD is a disease separate from MGD. If that were the case, Rynerson posits, would we not expect to see ATD present before MGD at least a few times? Because aqueous insufficiency always seems to follow MGD, it does indeed suggest that perhaps these clinical presentations are related and caused by the same etiology.
The saying that “medicine does not advance with existing ideas” may be apropos. A solid understanding of dry eye disease, despite all of our best eorts, has remained elusive. In the interest of patient care, perhaps it is time we all thought outside the box of traditional dogma and consider this new biolm theory of dry eye disease. Every step of the theory is not only an individually proven scientific concept, but the assimilation of these concepts into one theory makes common sense.
- Davis TH. Proc Natl Acad Sci U S A. 2007;doi:10.1073/pnas.0610519104.
- Kivanç SA, et al. J Wound Care. 2016;doi:10.12968/jowc.2016.25.1.12.
- Rynerson JM, et al. Clin Ophthalmol. 2016;doi:10.2147/OPTH.S114674.
- What are biofilms? www.biofilm.montana.edu/biofilm-basics/what_are_biofilms.html.
- What are the key characteristics of biofilms? www.biofilm.montana.edu/biofilm-basics/key_characteristics_of_biofilms.html.
- Where do biofilms grow? www.biofilm.montana.edu/biofilm-basics/where_do_biofilms_grow.html.
- For more information:
- Eric D. Donnenfeld, MD, can be reached at Ophthalmic Consultants of Long Island, 711 Stewart Ave., Suite 160, Garden City, NY 11530; email: firstname.lastname@example.org.
- Edward J. Holland, MD, can be reached at the Cincinnati Eye Institute, 580 South Loop Road, Edgewood, KY 41017; email: email@example.com.
Disclosures: Donnenfeld reports he is a consultant for BlephEx, TearCare and Johnson & Johnson. Holland reports he is a consultant for BlephEx.