Dry eye back to basics, part 1: It all starts with tears
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Vince Lombardi: “Gentlemen, we are going back to the very basics of the game. This is a football.”
Max McGee: “Coach, could ya slow down a bit, please.”
For some 20 or so years now, I have crisscrossed our fair land giving talks about various aspects of dry eye disease (DED) to audiences large and small. If I am the only “entertainment,” I try to end each engagement by asking if the information I shared was helpful and if there was anything about either the specific topic presented or about DED in general that the folks in the audience might find interesting or useful. After giving a talk about the nasal spray Tyrvaya (varenicline solution, Viatris), Mohinder Gupta MD, one of the senior physicians in the audience, approached me with a request: Would I consider a series on the basics of DED as a refresher for experienced doctors and a launchpad for newcomers?
In the spirit of the great Coach Lombardi, of course I would! Herewith, then, is part 1, of who knows how many, on the basics of DED.
It all begins with a tear. Too few or too many. Effective in all aspects of the job or not up to the task. We who spend our professional lives submerged in the prosaic nuances of DED have an intense need to know what constitutes normal. Why are normal tears effective? What happens when disease takes root? How do our tears change when they appear for different reasons? And if they fail to appear, why?
Our patients, on the other hand, come at tears from a more poetic place: “Tears are the medium of our most primal language in moments as unrelenting as death, as basic as hunger, and as complex as a rite of passage” (Rose-Lynn Fisher, courtesy of Laura Periman, MD). We must try always to keep in mind that our patients have a deep emotional connection to their tears. Indeed, countless song lyrics and lines of poetry have been devoted to the meaning of our tears. This may explain the surprise patients experience when they learn that their symptoms have been caused by tears that have somehow betrayed them.
Before we talk about anything dry eye, we must first be familiar with what it is that constitutes normal. Homeostasis is a term that has been bandied about for some years now. Heck, the original prescription DED treatment, Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan), was named with the aim of associating the drug with this state of equilibrium: “REstore homeoSTASIS.” The lacrimal functional unit (lacrimal gland, meibomian gland, goblet cell) produces three distinct types of tears. Basal tears, those tears that are responsible for the minute-to-minute health and well-being of our eyes, are continuously produced at a rate of 0.75 to 1.1 g per day. Psychic tears are produced in response to an intense emotion; they tend to contain leucine enkephalin, a natural painkiller that is released under stress. Reflex tears are the result of a noxious stimulant such as a foreign body and are primarily aqueous and electrolytes.
As eye doctors, we are primarily concerned with basal tears. In health, they protect, moisturize and nourish the cornea. The precorneal tear film is in many ways the primary refracting surface for light entering the eye. Indeed, data have been presented at numerous conferences in the last 12 months showing that abnormal tear osmolarity alone can be responsible for blurred vision that approximates the effect of a grade 2 nuclear cataract. These tears must be present in a volume sufficient to cover not only the cornea but also the entire bulbar conjunctival surface. They need to remain smoothly on the surface of the eye for at least 8 to 10 seconds; an uneven tear film often results in intermittent blurring. Lastly, basal tears are dynamic, responsive to both internal and external stimuli.
Like blood, human tears are spectacularly complex. There are some 2,000 different molecules present in precise ratios to one another. Lipids and mucin stabilize the complex tear emulsion. Healthy tears come equipped with antimicrobial elements such as antibodies, interleukins, lactoferrin and lysozymes to ward off infection. Like the tasty stuff sitting at the bottom of your bottle of Italian salad dressing, normal tears have a complex mix of electrolytes and metabolites. Angiogenesis is represented by VEGF, and epithelial cell health is supported by the anti-apoptosis agent caspase-14.
Inflammatory cytokines, both pro- and anti-, deserve special mention. At the World Cornea Conference in 2022, Francis Mah, MD, presented simply brilliant work that he and his co-authors had done examining these markers of inflammation in tears. Subjects with DED (average eye dryness score, 73.5) were compared with individuals who did not have any dry eye (average eye dryness score, 2.4). Pro-inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha, among others, and anti-inflammatory cytokines IL-4 and IL-10 were compared in the two groups. Subjects with a high eye dryness score had statistically significantly higher cytokine levels (P < .0001). Confirming this DED effect, subjects with a higher Schirmer’s score had lower cytokine levels (P < .0001). Bravo Francis et al.
This is one of the reasons proposed to explain the beneficial effect of using Tyrvaya: increased production of “natural” tears. Knowing all of this about normal tears, it starts to make sense how hard it is to make an eye drop that can legitimately be called an artificial “tear,” eh?
As we move forward with a discussion about the basics of DED, followed by a primer on basic DED treatment, we should remain aware of just how wonderfully complex and marvelous our tears are when they are normal. How amazing they are. How nearly miraculously they work for most people most of the time. Just as cardiologists must be ever conscious that the heart they treat is much more that an electric pump to the patient, so, too, should we eye doctors remember that tears to our patients are equally laden with meaning and emotion.
“Then lost in that feeling, I looked in your eyes.
I noticed emotion and that you had cried. ...
A lifetime of questions, tears on your cheek.
I tasted answers.”
– Rush, “Tears,” 1976 (courtesy of Parag Majmudar, MD)
Thank you for the inspiration, Dr. Gupta. I hope this was a good start.
- References:
- Fisher RL. The Topography of Tears. Bellevue Literary Press; 2017.
- Willcox MDP, et al. Ocul Surf. 2017;doi:10.1016/j.jtos.2017.03.006.
- For more information:
- Darrell E. White, MD, of SkyVision Centers in Westlake, Ohio, can be reached at dwhite@healio.com.
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