What do dry eye tests mean? (Part 6) Inflammation (and how we measure it).
Inflammation is at the heart of dry eye disease. This is relatively obvious, as dryness causes irritation and irritation begets inflammation - fueling the vicious cycle of dryness and damage.
Red Right eye inflamed from glaucoma medications and dry eye disease - left eye had Durysta implant to reduce glaucoma medications - redness and dryness improved!
At the surface of the eye, inflammation causes redness, heat, swelling, pain and ultimately loss of function. The redness is a product of dilated blood vessels and the heat is a byproduct of increased blood flow. Dilated vessels carrying “defense products” from our immune system, will cause the vessels to get leaky - and the oozing of fluid through these leaky vessels causes swelling. The defense products (I like to refer to as “human napalm, handgrenades and bazookas” - but are really called cytokines, chemokines, antibodies and ultimately white blood cells) will put pressure on -and cause irritation to - the nerves around them (causing pain). This stimulates reflex tearing and leads to blurring vision - and may ultimately inflict damage to the eye’s surface. This warfare will affect the cells and glands that would make the “good tears” leading to increasing levels of salty tears and dryness - eventually damaging the cornea (or clear window of the eye - so loss of function). And this all relates to “common dry eye” - whereas autoimmune dry eye takes this to an entirely higher level (by adding ““human smart bombs” to the off-kilter immune defenses, aimed at the water producing glands - see my posts on this here: https://www.eyethera.com/blog/sjogrens-disease-autoimmune-dry-eye-part-1 through part 5 here: https://www.eyethera.com/blog/ogh4ia5gewpejt9cszlk0emeccuzh3
The “Need to know” has pushed science and technology to develop tests and time-tested methods to help detect and measure degrees of disease - and dry eye disease is no stranger to this need. The simplest method to detect inflammation is observation - looking for redness, heat, swelling, and surface damage. Pain is more subjective but the sense of irritation and pain is best tracked with validated questionnaires (see my first post on testing here: https://www.eyethera.com/blog/what-do-dry-eye-tests-mean ). Surface damage is commonly measured with staining dyes and excess salt levels quantitated in testing I’ve discussed in this same series. Some Keratographers (Oculus R-scan) allow more objective measurements of redness and thermal imaging cameras can provide information on heat elevations from inflammation.
Inflammadry Test kit (positive test indicated by pink stripe with blue control)
One of the newer tests for inflammation involves a rapid, in-office test that looks for a certain immune system “biomarker” that has been shown to be common to the dry eye pathway of inflammation, so-called “matrix metalloproteinase 9” (MMP-9). Quidel makes this test - called “Inflammadry” - and using a technique familiar to most, it looks like a “CoVid test” in terms of a blue control mark and a pink positive mark. Like the CoVid test, itis either positive (pink) or not (no pink) - so it is not a quantitative test (there is no gradient validated to measure the amount of MMP-9 in the tear - only that it meets or exceeds a certain amount considered abnormal). There is a Dacron spongy segment that needs to sit against the conjunctival membrane of the eye and “soak up” enough of a tear sample to give an accurate reading. The initial study report states: “As MMP-9 is a nonspecific marker, many conditions other than DE (Dry Eye) can produce a positive result. This information is found in the package insert and includes conditions such as recent ocular surgery, infection, or allergic conjunctivitis. The package insert further states that false negative results can occur in the setting of systemic immunomodulators, topical or oral steroids, cyclosporine, tetracycline, and topical azithromycin, all of which may inhibit metalloprotease activity. The test should be avoided in patients with cicatricial conditions that could lead to conjunctival injury or allergies to cornstarch, Dacron, topical anesthetic, or fluorescein dye.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580996/
Because the majority of my dry eye patients have obvious amounts of inflammation and have eyes that are already uncomfortable from dryness, I’ve generally found this test to be more uncomfortable for the patient than the worth of reading a “positive” test (and if it’s negative, I’m not sure I always believe that, since many are already on some type of anti-inflammatory treatment and some are so dry it is hard to collect enough tear for a valid sample). Once a method becomes available to get a quick read on the amount of MMP-9 (hence the degree of inflammation present), then I’d be more inclined to want to measure that (especially if it was as easy and less irritating, as the salt testing I mentioned in the last post). Of interest to me, one of the more common pathways for MMP-9 to become elevated is for the salt levels to rise and “stress out” the cellular surface of the eye - so when the salt test shows high levels of salt, then a positive MMP-9 test can also be predicted.
More helpful, can be the Quidel test for the adenovirus common to causing pink eye (viral conjunctivitis). Since an eye can turn “pink” for a large number of reasons (including dry eyes and/or to many preserved drops like artificial tears or glaucoma medications - like my patient above) - and since this virus is extremely contagious, it can be useful to identify a viral cause when it exists (treating redness with a steroid makes sense when the redness is from dry eye-related causes, but using a steroid to treat a viral cause can allow the virus more time to evade the healthy immune response and cause the eye greater grief when the steroid is withdrawn). This test is also like a CoVid test (and a nasal swab for CoVid is often also indicated, since that virus is another highly contagious cause for pink eyes these days).
One of the reasons eyes can feel relatively “normal” even when many of our dry eye tests appear to show even severe levels of dry eye disease, has to do with corneal sensitivity. I touched on this point in my earlier blog post here: https://www.eyethera.com/blog/the-hill-of-sorrow-and-how-getting-better-can-sometimes-feel-like-getting-worse It is especially helpful to evaluate for reduced sensation of the eye’s (corneal) surface when we see this “disconnect” between how a patient reports they feel and how we think the eye probably should feel. A variety of tests are evolving to help detect and then quantitate this feeling - from as simple as asking if a patient feels a typically irritating drop when it is placed on the eye (and grading that response on a scale of 0-10), to testing with wisps of cotton, fragments of fishing line or pulses of air. Confocal microscopy (a special microscope that can scan the cornea with high magnification) can help detect abnormalities in the nerves that can help further explain such relative “numbness.” Fortunately we now have many tools to help bring nerves back (as nerves are important to the production of tears and serve as a necessary impulse to good blinking) - and the “Hill of Sorrow” post helps explain more about that, too!
To schedule an appointment with Dr. Jaccoma, call Excellent Vision at either of these two dry eye offices:
(1) 155 Griffin Rd, Portsmouth, NH 03801 (603) 574-2020
(2) 3 Woodland Rd, STE 112 Stoneham, MA 02180 (near Boston) (781) 321-6463