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News Updates - more bad drops on the market and a new kind of “punctal plug” - Lacrifill!
First the bad news - FDA warnings about drops that could infect or injure you, continue:
”[1/31/2024] FDA is warning consumers not to purchase or use South Moon, Rebright or FivFivGo eye drops because of the potential risk of eye infection.
These are copycat eye drop products that consumers can easily mistake for Bausch + Lomb’s Lumify brand eye drops, an over-the-counter product approved for redness relief.” https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-contaminated-copycat-eye-drops?fbclid=IwAR085_VOsxm-9x0CtykAzUJF2Fb4Rn2nQzBFAd7HYsdwc6EBKu31z9hy_jI_aem_AfyHpReFyoRIaWRypfQKaucUi2WHDOhHkA7HxmLNfxqe1dwwFHXGJmlWgjMWkFb2a-A
I posted on Lumify (and other eye whiteners) - and the risks taken even with on-brand drops like these here: https://www.eyethera.com/blog/can-i-use-eye-whiteners-like-visine-or-lumify-when-my-eyes-get-red
Now the better news -
April 7, 2024, I attended the American Society of Cataract and Refractive Surgery annual meeting. While I no longer perform cataract or refractive surgery, I see patients who have cataracts, and who may be planning cataract surgery, nearly every day in my clinical dry eye practice. I’ve posted on cataracts and dry eyes here: https://www.eyethera.com/blog/dry-eye-cataract-and-glaucoma-segment Control of the ocular surface is critical to a good outcome with cataract surgery, so I am often involved in the pre (and post) operative care of these patients. During that meeting, a new punctal plugging product. was rolled out, called “Lacrifill.” It is basically a sugar gel like “Juvederm” or “Restylane” (a natural “hyaluronic acid” compound found in skin and eyes) that has long been used as a filler in cosmetic procedures and in cataract surgery. It will gradually dissolve into sugar and water, so needs replacement approximately every 6 months (& may last a bit longer - or less long, for some). If it works “too well” and results in chronic, unwanted tearing (down the cheeks), then a salt water solution can be used to rinse it down the “plumbing” into the nose. There is also an enzyme that can dissolve it in cases that a simple rinsing doesn’t work (expected to be rare). Insurance is expected to cover it, as a plugging procedure, but it’s possible that some may require a “prior authorization” approval process. Punctal plugging is not for everyone (I’ve blogged about this before: https://www.eyethera.com/blog/what-about-punctal-plugs-or-why-not-dam-up-those-damn-tears and https://www.eyethera.com/blog/when-tears-dont-drain-properly-you-get-toxic-soup-and-the-toxic-soup-syndrome
While these prior posts cover most of the potential “negatives” involved with blocking the normal flow of tears from the eye to the nose, it is true that there are numbers of patients who will significantly benefit from such tear duct closure. Keeping more tears (and any medicated products) on the surface of the eyes is hepful when the tears are “good tears” but just too little to do their job. A potential benefit of this unique use of sugar gel, is the “soft” and “sticky” quality of this natural filler. This means no “plastic” is exposed to the delicate membranes of the eye, and nothing to “fall out,” which is a common problem with the plastic plugs that are “wedged” into the tiny tear duct openings along the inner eyelid margins. Lacrifill can “hug” the passageways leading from the eyelid to the nose, blocking tears along the entire way.
A few key points - as a sugar gel, the reason it doesn’t instantly “dissolve” into sugar and water, is due to the “crosslinking” where the sugar molecules are bound strongly to each other. Natural enzymes break these links down over time and the more “links” in the chain, the harder it is to break down. Staying soft and “gel-like” means that excessive manipulation (squeezing, massaging, rubbing) may cause some gel to “burp out” of the tear duct (either into your tears, or down your nose), so avoidance of excess manipulation near the tear drainage area should generally be avoided with this product (especially in the first days of instillation, as most sugar gels tend to “set up” and become more locked in place as they mature in their position). If too much burps out and into your tears, this leaves a portion of the duct “empty” with a blockage in place closer to the nose. Typically, this can lead to a “stagnant pool” of tears where germs can thrive and potentially cause infections. If the area of the lids closer to the nose become infected, then sticky yellow-to-greenish discharge and/or redness, swelling, tenderness and warmth of that area can indicate an urgent need to see your eye doctor.
As usual, I recommend working with a dry eye specialist to get the best results for your dry eyes.
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
Making Tears Part 8 - More on Making Proteins…
A couple of posts ago, I referred to the intricate “bakeries” inside the castle walls (which I count as the Lacrimal Gland), where production of proteins like “Sir Lact,” “Sir Lyse” and a whole army of defensive “Knights” occur to keep the realm (the eye) safe. Outside the castle, there are the “rolling fields” of conjunctiva (the smooth, clear membrane covering the whites of the eyes) as well as the cornea (the window or “watch glass” we see through). Among that membrane field are tiny cells I referred to as the “Peasants” working that field. Served by blood vessels carrying proteins and other nourishing products, these Peasants (called Goblet cells”) can “belch out” a special, sticky protein, called mucus. Their distribution is not evenly spread across the landscape, but the “mixing action” of a blink can help distribute their sticky products over the surface of that realm. Because the surface would be very slippery without this “peanut butter-like substance” to help adhere, a key attribute of this product is the very sticky nature that interacts with the salt-watery tears floating above that layer and allows it to spread its goodness while acting as another barrier to any “badness” that would like to attack that surface. As sticky as it is to the cells below the tears, it has unique properties that makes it hard for germs to get to - and stick to - that surface!
The nose-favored distribution of the “Protein Factories” called “Goblet Cells.” (tiny dots are the cells with some clusters as larger dots. N stands for Nose).
From: Gipson IK. Goblet cells of the conjunctiva: A review of recent findings. Prog Retin Eye Res. 2016 Sep;54:49-63. doi: 10.1016/j.preteyeres.2016.04.005. Epub 2016 Apr 16. PMID: 27091323; PMCID: PMC4992623.
The Calcium “tokens” play a role in switching on the production of that sticky protein and the hormone messenger, Vitamin D, has receptors that it can bind to, and help in increasing the supply of Calcium - which can initiate greater protein production. Vitamin D has come under great medical interest, as it has similar mediating roles around the entire body - and the deficiencies of Vitamin D common to many of us in the North East, means many of my dry eye patients are at a disadvantage, since natural sources of Vitamin D come from exposure of the skin to the sun, and in this area winters are long, winter days are short and often cloudy. Primary care doctors are increasingly tuned in to monitoring Vitamin D levels and often recommend Vitamin D3 supplements. Cod liver oil, a prime source of Omega 3, is also a good source of Vitamin D and it is part of the supplements I recommend to most of my patients. Around the “mouth” of these goblet cells is a “belt-like” band that can help regulate the “belching,” by adjusting the size of the opening that would allow the proteins to escape (a bit like a chimney flue that regulates the escape of smoke from a fireplace). As the concentrated protein escapes, it mixes with water and “blooms” into the sticky paste we call mucin or mucus.
But Goblet cells are not just “protein factories,” indeed they appear responsible for the water expressed from the conjunctiva itself. Using my “sprinkler and fire hose” analogy, the Goblet cells produce “Claudins” a type of chemical “worker” that can open little water channels in the membranes of the Goblet cells and help regulate their “sprinkler function.” The Lacrimal Gland is the primary source for the dousing of salty water I refer to as the “fire hose” - so that water can really flow when it is most needed.
Production of these important Goblet cells, comes from unique stem cells - different but related to the stem cells that cover our corneas with their specialized cells. They have an interesting biological clock that produces crops of these “peasants” based on a cell-doubling calendar. Most of the time they crank out epithelial cells - the tough “tiles” that make up the resilient cover of our membrane, but at regular intervals, they switch gears to produce the Goblet cells! Inflammation appears to affect production of these Goblet cells - and allergies, infections and self-induced irritation (as in Mucus Fishing) are well known factors in increasing their protein production - see my post on this here: https://www.eyethera.com/blog/when-eyelids-are-irritated-including-allergies-such-as-to-our-best-friend-pets
Not all proteins produced by Goblet cells are the sticky things outlined above - some have additional sugar complexes that make them uniquely suited to assist in repair of the corneal surface (think of them as the medical emissaries or local “Red Cross” if such a thing existed in our Medieval world). Genetic tweaks in the production of similar Goblet cell proteins can lead to a real world autoimmune disease - Ocular Cicatricial Pemphigoid (OCP - mentioned in my autoimmune posting - now called “mucous membrane pemphigoid” - see the next link, below), where the surface progressively scars and can lead to exceptionally dry surfaces that can result in blindness for those not sufficiently diagnosed and treated.
Cyclosporine (medications like Restasis, among others) has anti-inflammatory properties that can lead to as much as a 2-fold increase in the number of Goblet cells (by reducing the inflammation that reduced that number), as well as an increased water production (and overall “sprinkler system” tear volume) for our tears. This appears relatively unique among anti-inflammatory medications and may be especially helpful for those patients suffering from reduced mucin (common to those with significantly advanced dry eye disease called “Aqueous Tear Deficiency” - see my prior posts on water, including: https://www.eyethera.com/blog/when-the-sprinkler-system-dries-up-and-autoimmune-testing-is-negative-whats-up ). Vitamin A also plays a role and while we know too much Vitamin A has been associated with MGD (Accutane for one), some amount is needed for proper Goblet cell development and activity. In fact, the brain-eye “axis” development is heavily dependent on Vitamin A from conception. Because Vitamin A can be produced as needed from a diet rich in leafy green vegetables, this appears yet one more reason to include these foods in your diet!
Many diseases wage war on Goblet cells - allergies, Autoimmune diseases (i.e. Stevens Johnson Syndrome, OCP, Sjogren’s, Graft vs Host) as well as advanced dry eye disease, radiation and even blepharitis (see my many posts on that issue). Keeping Goblet cells healthy is one more goal for dry eye doctors to have for their patients - those poor little Peasants are no less noble than the Knights, Kings and Queens, when it comes to keeping a healthy, happy realm.
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
Making Tears Part 7 (the all-so-important oil glands!)
While there is no debate that water, salts and proteins are principle portions of the tears, it is the fine layer of oil floating on top, that seals in that moisture and lubricates - while supporting and protecting the eye. The production of oil involves a complex cycle of life from “mother cells” (called “stem cells”) who produce “daughter cells” (called “progenitor cells”) that in turn birth “oil cells” (called “meibocytes”). Mother cells exist near the surface of the lid margin and along the “tunnels” (ductules) leading to the “chambers” (acini - the “balloon-like” “rooms” off these passageways). Their progeny or daughter cells can migrate into these chambers and produce the oil cells or meibocytes, where they “hatch” into little puddles of oil.
While this sounds surreal, simply because it is a complex process, one can understand that there can be many pitfalls which can weaken the “supply chain” otherwise leading to this oil production. Add that it is necessary for the force of a blink to “flush out” and empty these chambers - and we begin to see the kind of trouble leading to “Meibomian Gland Dysfunction” (or MGD). I’ve posted much on the basics -the importance of oil and its production, as well as various tactics to improve oil production, in earlier blog posts: https://www.eyethera.com/blog/how-important-is-oil-to-our-tears , https://www.eyethera.com/blog/how-do-we-fix-the-oil-problem, https://www.eyethera.com/blog/you-are-what-you-eat, https://www.eyethera.com/blog/why-do-my-oil-supplements-not-work , https://www.eyethera.com/blog/why-do-expensive-dry-eye-treatments-fail-and-what-is-maskin-probing , https://www.eyethera.com/blog/more-on-mgs-the-tear-oil-glands , but to distill it down to the present level of discussion, I can add a few extra thoughts.
Remember the “peasant diet?” Fish, nuts and seeds, whole grains, and legumes - not only supply Tryptophan, leading to Serotonin and Melatonin (see earlier posts in this series), but also provide the (3) Essential Free Fatty Acids - the “oil building blocks” called Omega 3, 6 & 9. Without a steady supply of these essential oils in our diet, the mother and daughter cells making the oil cells are just as hampered as a mother trying to birth a healthy baby when they are malnourished. Toxins (potentially from pollution, makeup, medications like Accutane or other retinoids - or from germ warfare on our lid margins, among other stresses) can weaken and kill off these maternal cells. Inflammation can undermine the foundation of the walls supporting the tunnels and chambers, leading to strictures and “dead ends” that can block the passageways required for flushing out the oils produced in those chambers. Too much inflammation can weaken our troops and act like a fire that can burn down the village.
When oil doesn’t move along as it should - it becomes stagnant, rancid, nasty stuff that by degree tends to “gel up” and turn into the kind of waxy products better suited for making candles than it is for making tears. Once the lids become aware of just how bad the oil has become, it senses it as the “enemy” and inflammation will attempt to wall it off. From what I read about sanitation in the Middle Ages, walling off unsanitary stuff was about all they could do when modern plumbing didn’t exist - so maybe our lids aren’t all that different? Unfortunately, this can lead to our inadvertently damaging these oil producing glands. Caught early, it is often easy to “fix” this problem - but when allowed to progress, then styes and withering are the common outcomes - followed by ever decreasing amounts of oil production. I’ll direct readers to the above links for more clinical information on these topics and look deeper into the protein factories called “Goblet Cells” next time.
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
Making Tears Part 6
Regulation is the key to running an efficient, effective realm, no matter what era or place is involved. In the case of dry eye disease, this is especially true, as this is where regulation has often gone amiss of our healthy aim. Cortisol (a messenger from the adrenal glands) is responsible for helping us in coping with stress. I see it as the emissary sent to warn of an impending enemy “siege,” and sets in motion the ability to free up energy and promote the “S” camp to “protect the realm” from the “attacking Huns,” with its emergency rations and protective reflexes. The problem is that we can only stay on this level of “high alert” for so long, before we begin to literally “break down.” This is another way of saying that reducing stress levels and the cortisol levels related to it, is important for restoring “normalcy” to the daily functions of the castle and protect the general health of its populace. Other ways we raise our cortisol levels is with alcohol. As little as 2 ounces of alcohol can raise this level and set us on this “S” pathway for days. Illness will also activate cortisol production, so staying physically healthy is key to eye health as well as general health. (Often easier said than done.)
Caffeine is a powerful “S” camp activator as well. It sends a message to prepare for “Flight or Fright,” where our heart rate, blood pressure and breathing rate is increased. This may help us prepare for our often stressful days ahead, but does take some toll on the tear glands and the surface of our now “saltwater -rather-than-salad-dressing-drenched” eyes. While we may not be able to easily regulate the amount of stress in our day, we can regulate the amount of caffeine and alcohol we take in. Both can adversely affect sleep, so caffeine is best consumed early in the day and alcohol in moderate amounts early in the evening. For those suffering significantly from dry eye disease, avoiding all forms of caffeine and alcohol can often be a game changing strategy.
Sleep and rest are the gifts that elevate the “PS” camp activities that restore the “salad dressing” and replenish the stores of healthy tear products that were "burned up” by the “S” camp. Melatonin is the “sleep hormone” that sets sleep in motion and can be promoted by “winding down” from online and TV/computer/gaming and phone/online activities a few hours before bedtime. I posted on issues relating to sleep here: https://www.eyethera.com/blog/do-blue-blocking-glasses-help-with-dry-eyes - and relative to the “peasant diet” as it can affect sleep, here: https://www.eyethera.com/blog/making-tears-part-2
Inside the cells lining the inner eyelids and white part of our eyes, live “protein factories.” Inside these “castle rooms",” coded messages (Messenger or “mRNA”) work with the protein architects (called ribosomes, I think of them as “bakers” and the “recipe” comes in the form of mRNA). The baker collects the necessary ingredients and then mixes them together in the “mixing bowl” called the Endoplasmic Reticulum (ER). This gets passed along by way of “chaperones” into the “oven” called the Golgi Apparatus (GA). Once “baked” into the form required by the recipe, little “sacs” can pass them through the “wall” of the cell membrane and release the final product into the water seeping through the same membranes. Again, the “salty tokens” help regulate this exchange and are driven by programmed codes that help regulate all cell life.
Salts can be similarly stored and passed through the membranes, to join the protein-laden water. At this point, we have the water, salt and protein forming the essential 3 parts of our “tear salad dressing,” but to get to the ultimate tear, we need to add oil. We also have signals in the way of nerves and hormones to regulate the volume and ultimate recipe of our tears. In future posts, I’ll attempt to explain more of this interesting and essential process. I can also share that eyes prone to repeated infections may have some difficulties in producing “Sir Lyse and Sir Lact.” Others may lack some of the antibodies and other protective mechanisms common to most people. Science continues to “drill down” on these deficiencies and continues to look for remedies.
One example of this “Better living through chemistry” act, is understanding - and modifying - our protein messengers. G-proteins are important Medieval “Pages” - messengers that couple with cells at the “in box” to affect the activities of the cell. In a remote region of the realm (the brain’s hypothalamus) these messengers can be dispatched to circulate throughout the “aqueducts” (blood vessels) and reach the targeted tissues (in our case, the tear producing “machinery”). OKYO Pharma has apparently capitalized on one of these “Pages” (for a fuller scientific account, see: https://okyopharma.com/okyo-pharma-announces-ok-101-successfully-achieved-statistical-significance-for-multiple-signs-and-symptoms-of-dry-eye-disease-including-ocular-pain-relief-in-its-first-in-human-phase-2-trial-of-ok-10/ - A quote from this article about the drug they’ve named OK-101, explains it succinctly: “OK-101 is a lipid conjugated chemerin peptide agonist of the ChemR23-protein coupled receptor which is typically found on immune cells of the eye responsible for the inflammatory response. OK-101 was developed using a membrane-anchored-peptide technology to produce a novel long-acting drug candidate for treating dry eye disease. OK-101 has been shown to produce anti-inflammatory and pain-reducing efficacy signals in mouse models of dry eye disease and corneal neuropathic pain (NCP), respectively” and Okyo Pharma “announces additional statistically significant findings in results from Phase 2 trial of OK-101 (0.05%)” - so by making a drug mimicking a G-protein “Page” we now may have a way to target the “Knights” who may have gone too “rogue” and would otherwise cause inflammation-related mayhem in corneal nerves and tear gland tissues. Understanding the cellular level of how our bodies work can allow science to help put our bodies (and eyes) back on a peaceful track and improve the quality of our lives.
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
Making Tears Part 5
In previous sections of this series, we’ve learned about some of the many proteins and salts making up our tears - but we have yet to discuss where (and how) we get the water. It should be obvious that every element of our tears ultimately comes from our diet and digestion (and the many, tiny germs relevant to that digestion process) - and no surprise that the water comes through our gut as well. I’ve covered much of this in prior posts, but how do the tiny cells in our lacrimal gland and scattered over the smooth membranes covering portions of the eye and eyelids ultimately regulate and produce that water? Remarkably, scientists continue to be befuddled by this process, but much has been learned from studies (largely using rodents). I’ll use some artistic license around my medieval analogies to help explain what I know about this interesting process.
Remember those salty “tokens” we called sodium and calcium “ions?” These tiny, “charged particles” have an electrical nature which allows them to bind and then “flip switches” in cells. Pathways open, allowing materials like water to pass through otherwise watertight membranes - and water likes to follow these ions - so cellular “pumps” can be triggered and run by these tiny tokens. Scientists refer to this production of water as “transepithelial” - indicating that the water literally passes through these (epithelial) cells and around or through the binding agents acting as the “mortar” between these cells. Of equal interest is that there are “protein factories” inside these cells that make the products (like Lactoferrin and Lysozyme) which can be transported into the water that becomes our tears.
Flow is a highly regulated process involving the “telegraph wires” (a neural network), as well as local and distant messengers (proteins and hormones). Some merely open or close the “aqueducts” (blood supply), so more water is delivered to the tissues. The “S and PS camps” (Sympathetic and Parasympathetic Systems) are good at this part of the regulation and many drugs have activities in this realm. A good online source for finding medications related to the “S” camp can be found here: https://go.drugbank.com/categories/DBCAT000438 but the effects are complex, as these messengers not only increase circulation, but also may stimulate muscles which open lids further (those knights on horses pulling the carriage around), which will expose the eyes to evaporation (and drying out). The “S” camp is also primarily responsible for the “fire hose” or emergency backup system making the salty tears we actively cry with (the buckets of fire-prevention water we make when sad, when something gets in our eyes or when the sprinklers let us down). The “PS” camp has an equal resource here: https://go.drugbank.com/categories/DBCAT000448 and is generally responsible for the "“sprinkler system” making the “salad dressing” of a healthy tear.
It is not uncommon for me to find dry eye patients on dozens of medications, treating a wide range of symptoms and maladies. Some of these drugs are countering side effects of one another, which can relate to these 2 opposing “camps.” Sorting out which medications are truly necessary - and weeding out those that are less necessary (or only used as counters to side effects that disappear when those medications are weeded out) often requires input from the various doctors who prescribed them - so it can take a literal “village” to help an average dry eye patient. Our eyes, like our bodies, are a complex chemical factory, with all the general issues for successful survival and flourishing, as those “medieval realms” - adequate nourishment, rest, support, protection and order. Without proper elements of each, chaos and “plagues” can take us down. More on this internal and external regulation next time!
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
Making Tears Part 4
Ah, Sir Lyse. Lysozyme is an enzyme that dissolves the sugary protection around bacteria and causes them to dissolve or “lyse.” I think of that sugary protection as a kind of chainmail mantle, since it is designed to allow some bacterial needs in and bacterial bad things out - but otherwise protect like a chainmail mesh can do. This mesh is the foundation of the bacterial cell wall, the protective envelope those wicked little assassins have as their best defense. Like the wicked witch in the Wizard of Oz, once the protective “spell” of this chainmail is lost, the bacteria is “melted” - like pouring a bucket of water did to her. As you can see from the table below, tears contain the greatest amount of “Sir Lyse” compared to many other natural sources.
Table 1 (from Nawaz N, Wen S, Wang F, Nawaz S, Raza J, Iftikhar M, Usman M. Lysozyme and Its Application as Antibacterial Agent in Food Industry. Molecules. 2022 Sep 24;27(19):6305. doi: 10.3390/molecules27196305. PMID: 36234848; PMCID: PMC9572377.Selected sources of lysozyme.)
Source of Lysozyme Amount of Lysozyme
Tears 3000–5000 µg/mL
Chicken egg white 2500–3500 µg/mL
Duck egg white 1000–1300 µg/mL
Goose egg white 500–700 µg/mL
Human milk 55-75 µg/mL
Cow milk 10–15 µg/mL
Cauliflower juice 25–28 µg/mL
Cabbage juice 7–8 µg/mL
Papaya juice 9 µg/mL
Spleen 50–160 mg/kg
Thymus 60–80 mg/kg
Pancreas 20–35 mg/kg
According to this same article, “Lysozyme is an important part of the innate immune system and exhibits strong antimicrobial activities against bacterial, fungal, and viral pathogens. It protects against infections, acts as a natural antibiotic, and enhances the efficacy of other antibiotics, while it also strengthens the immune system.” This sounds a bit like Sir Lact (Lactoferrin) - and helps us understand how, when mankind was living in dirty caves and hovels, we (through this roundtable of shining knights) were able to sustain ourselves against the many diseases that would otherwise have wiped us out. (Interesting that even plants like cabbages and cauliflowers can contain some amount of Sir Lyse - and how, at some basic biological level, our tears reflect eons of evolution that. even include the plants we also survive on).
Further, “The protein was suggested to conduce to the destruction of tumors, as it modulates the synthesis of the tumor necrosis factor (TNFα) and also stimulates the production of Type I interferon (INFα, INFβ, INFγ), interleukin-2 (II-2) and interleukin-6 (IL-6) by human lymphocytes [7]. In the current pandemic of the coronavirus, some modified form of lysozyme can be used to stimulate the formation of interferon, an effective substance against coronavirus, and thus reduce the risk of the life-threatening form of COVID-19 up to 79% [8,9].”
Apart from Sir Lyse, Sir Lacto and our antibodies, we have other “protectors of the realm,” including tear-specific prealbumin (TSP or lipocalin) and peroxidase. Add to that the natural “washing function” of blinking away old, dirty tears and replacing them with fresh, healthy tears and we have a robust defense system. Even as pathogens evolve to take us down by “getting smarter and better armed” - so we too can rely on our defenses to evolve - and, with modifications, keep up with these tiny infidels, assassins and assorted mercenary troops. Eyes are precious and it’s good to know we can protect them with our tears (and with our strides in science that allow us to create medicines, vaccines and strategies that can aid our innate defenses).
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
Making Tears Part 3
For those interested in the relationship between sleep, diet and health (and don’t mind some technical talk), this is a good place to start: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511346/#:~:text=Tryptophan%20is%20an%20essential%20amino,and%20legumes%20(Table%201).
Getting back to the basics of a tear, this “salad dressing” consists of surface “oils,” a mid-layer of salty water and an inner layer of proteins described as the mucus layer. While each element has specific functions - the primary functions involve transporting oxygen to the surface cells (this is where the salty water plays a critical role) as well as protecting and otherwise supporting them. The oil is a thin “slick” produced by the Meibomian Glands - which are “accordions” in the eyelids and are literally pressed into service by the squeezing pressure of a “good blink.” We will delve deeper into this part of the tear-making discussion later and refocus on the salty water and proteins, here.
If we can use simpler measures of volume to describe a tear (normally measured in microns), then 1-2 “ounces” of the recipe is oil, 7-8 “ounces” is the salty water and as much as 30 “ounces” is the protein “mash” (proteins and sugar complexes suspended in water) we can call mucus. Spread across the surface with a blink, this is the support needed by the “peasant” surface cells and needs to be sustained regardless of the environment (however cold, hot, dry or humid those conditions might be). Treachery in the way of infectious invaders, surface scratches (where a fingernail could be the equivalent of slings and arrows) or siege (the effect of too much staring - so the supply of fresh tears is interrupted and the peasants “go without”) will call on support from within and without the castle walls.
When various messengers (there are many, but include Acetylcholine or ACh and Vasoactive Intestinal Polypeptide or VIP) arrive by way of the major roadways (in our case, nerves and blood vessels), they’re received by their own, external messengers (G-proteins) and make their way to the cell “factories” making the protein products and regulating the transfer of water - largely regulated by Calcium ions (the salty tokens that open these cellular pathways). Other proteins like Immunoglobulins (IgA) are produced by specialized “plasma cells” that can arrive from the gut by way of the blood vessel roadway and can sit amongst the Lacrimal Glands “normal” cells. This appears to be a pathway for the “Gut Associated Lymphoid Tissue” (or “GALT”) to bring immune functions learned from interaction with gut germs to bear on eye protection - but may also open the door to malfunctions leading to autoimmunity (where they become traitorous and inflict damage on normal cells instead of abnormal invaders).
When it comes to fighting germs, protection from “within” comes from a number of “on site” agents. We would get deep into the weeds if I attempt to single out and discuss each one, but there are a few that deserve significant attention here. I’ll begin with Lactoferrin - I see this as an exceptional band of knights who are present in tears and throughout the body - more heavily present in the smooth, moist membranes where germs are likely to first approach us. I’ll refer to this element as “Sir Lact” (yes - lac or lact is derived from the latin word for mik and Lactoferrin is highly present in milk - probably to ensure the offspring being sustained on that milk will have an extra opportunity to fend off infections until they can mount their own vigorous defense system). Sir Lact has the ability to bind iron (so essentially cloaking himself/herself in armor, while denying his foe the same). Iron is critical to bacterial survival and Sir Lact can not only deny them their iron, but also directly damage the membranes of these microbial foes - while signaling other members of our defense system to attack. Interestingly, Sir Lact also helps to control cellular oxidation (think of this as “biological rusting” - and this process of oxidation puts stresses on cells (good or bad) and controlling inflammatory responses - so controlling these processes may help us “age slower,” as well as helping us deal with some of the root causes involved with many neurological diseases (Parkinson’s and Alzheimer’s, to name two), many autoimmune diseases (like Sjogren’s and Rheumatoid Arthritis, to name two more) and cancers (too many to name). Sir Lact appears effective against many bacteria (including some who would be resistant to many of our modern-day antibiotics) and also many viruses. He/She can potentially fend off attackers so we have more time to recognize them and call in specific antibodies and other immune responses that can be more specifically directed to kill those foes. Sir Lact works well with other members of a tear’s defenses, including “Sir Lyse,” (Lysozyme) who will be heavily featured next time.
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
Making Tears Part 2
When visiting Poland a number of years ago, I had a chance to experience their renowned salt mines and - by visiting some museums and a castle, to gain an appreciation for what it meant to be royalty in the Middle Ages. (If any of you get the chance, I’d highly recommend a tour there.) This creates the next level of our discussion, as salt was a form of currency - so important and highly sought after as it was - and so critical to the production of our tears! For a detailed history of the salt mines, I recommend:
First, not all salts are Sodium (what we commonly think of as table salt) - and Calcium (another common salt vital to our lives) plays an important role in tear production. Calcium ions can be seen as tokens that open gates across membranes (I liken them to the gates in the cell or “establishment” walls that allow movement in and out of that establishment). Sodium also plays an important role and can “carry” the water in and out of the cells.
Regulation of these establishment activities (producing the salt-watery part of the tears) occurs from two “camps” - (Sympathetic and ParaSympathetic - we’ll establish them as the S and PS camps). Acetylcholine (ACh) is the messenger of the PS camp and generally tells the establishments within the larger castle (Lacrimal Gland) what to do regarding the basic, daily tasks of tear production (how many buckets of salty water are needed to sustain the surface of the eye - perhaps we can see those surface cells as the peasants). This establishes the daily rations - but is heavily influenced by the S camp (which communicates by epinephrine as well as a host of other hormones/transmitters). The “flight or fright” response of the S camp is the call-to-action responsible for emotional and reactive or “reflex” crying and can substantially increase the volume of rations (which has the benefit of washing away damaging irritants, apart from social responses).
Many of the finer aspects of hormonal influences remain poorly understood, possibly because there are too many “voices” at the table at any given time. The “Feudal Lord” ruling the Lacrimal Gland “castle” has many “advisors” (known as the biological “receptors” - or, in this analogy, the “ears” of these advisors). They get their messages from the many hormones and transmitters sent directly from the "King or Queen” as well as less directly, from the many hormone centers throughout our bodies.
One hormone called Serotonin appears to play a pivotal role in tear production (based on mouse research). Serotonin is best produced by a diet rich in Tryptophan, which is an essential amino acid found mostly in animal products, as well as in nuts and seeds, whole grains, and legumes. This “peasant diet” - good for producing Tryptophan - contributes to production of Melatonin - the sleep hormone - and since sleep appears to be linked to health in general and to production of healthy tears in particular (in this conversation), it is easy to begin seeing the underlying links to this happy “Medieval life.” (We will circle back to the essential Omega Oils found in fish, nuts and seeds when we get to the Meibomian Glands and their oils).
We’ll delve into more of that “Round Table” discussion next time.
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
Making Tears Part 1
To learn how tears are made, it is helpful to understand the elements in a tear, as well as the hierarchy of signaling and basic arrangement of glands and tissues required. for that production Most will appreciate how the brain is the key regulator - King (or Queen) to their servants, including, in this analogy, the organs and glands that define our bodily actions.
Nerves serve as the telegraph lines (yes, telegraphs came much later in the scope of history, but it’s hard to imagine faster lines of communication in the medieval era), communicating these royal wishes to their servant subjects, In turn, these subjects send back their sensations - as reports and needs - by an alternate series of telegraph lines, so the Royals can serve and sense what’s going on around them. Apart from all this commotion, exists the most basic daily activities, including the making of tears. Furthering my medieval analogies, this would be the regulation of Peasants and more lowly Serfs, by Knights and their Lords.
I see each eye as a Lord, served by Knights (on horseback;) - acting as the muscles to move their Lords around in their carriages, (the orbit). Other Knights (with their own set of Serfs) exist to clean, nourish and protect them. Eyelid Knights are supported - outside - by skin and eyelashes (to shield from the elements) and are supported inside - by membranes, glands, and plumbing to make and distribute tears). Over all of this, a Round Table of Knights serve as a finely tuned defense system. These soldiers and their Serfs serve as the archers, water bucket carriers, catapult artillery, oil pot boilers,, swordsmen - you get the idea… Each have their own jobs to do in peace and war time - and their basic directives are governed by an automatic, (autonomic) system of rules and orders.
Blood vessel-bourne messengers exist as hormones (carrying larger decrees - often from far away glands like the thyroid, ovaries, testicles or adrenal glands) and smaller proteins (providing simpler directives that can be sourced more locally or further away). They coordinate with the telegraphed messages delivered by nerves, and break down into “rest’ (parasympathetic) or “work” (sympathetic) modes, with frequent overlap. Since our focus in this series is about the tears, it is important to discuss the basic elements of a tear and where they come from.
At its core, tears are made of water, salts, proteins and oils. Water is by far, the largest portion of a tear and it comes from several glandular sources and is under a complex neural control. Those telegraph lines are fairly buzzing much of the time and their messages are modified by hormones and proteins. Let’s dive into this next week!
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
Where do tears come from?
In posts past, I’ve spent a lot of time simplifying what is a rather complex process of how we make tears. This process is a bit like describing how we produce blood - and (less the red and clotting stuff), it is related, in that some blood products (antibodies, proteins, and other immune products) apart from salts and water, are shared. In fact, blood is the primary support for the glands making our tears, so that they can do their job - unsurprisingly, those with major blood problems can also have significant tear problems. In future posts, I’ll attempt to unravel some of the mystery and simplify as best I can about this amazing process. For those who crave the fuller explanation, there is an excellent, more physician-level resource available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501785/?fbclid=IwAR3V4f230p6T-Ucji0R3CygMOM03vU5WKxkrXAWrq9d0f-opp0uNnSVyeDI For now, I’ll stick to the Sprinkler System and Firehose analogies with tears being the lifeblood and the blink being the heartbeat. I still like the “salad dressing” and the “salt water” for our describing the two types of tears - but next week we can get a bit more granular with it. Until then, blink strong!
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
Why rub your eye?
Above video comes from: Defeat Keratoconus @defeatkeratoconus4856 and illustrates what happens to your eye when you rub it - much as you might see with Superman’s (or Superwoman’s) “X-Ray vision.”
Rubbing your eyes can feel good - and generally doesn’t have any immediate negative consequences - so it must be good for us - Right? Well, generally speaking, it’s more wrong than right. Watching the above video gives a unique perspective on what is going on when you do rub your eyes, but let’s consider the good and the bad.
Good news first. When you rub your eye, it is possible to help your eyes make tears. Pressure on the lids can force some oil out of the oil-producing (Meibomian) Glands and oil is an important (and often lacking) part of a tear. I’ve covered much of the benefits of oil in our tears - as well as the function and support of these glands - in many prior posts, so won’t dwell on it here. This pressure can also slightly irritate - and therefore stimulate - the “firehose” glands that create the gush of salty water useful for washing dust, pollen or other irritants out of the eyes. Like a cough, rubbing eyes can trigger the vagus nerve that can slow our heart rate. Mild slowing can help relieve a sense of stress, though major slowing can risk dizziness or even fainting - so this can be a good or bad side effect depending on how slow you go. I tend to separate the act of gentle wiping (generally good for spreading eyelash cleansing products around the lashes, removing loose lashes and excess tears from the lids) from the act of rubbing (exerting force against the eye by firmly pressing on the lids, as in this video - and the subject of this posting).
Bad news can be many - and magnified by underlying eye issues. When you rub your eye, it is possible to damage the cells making and repairing the collagen fibers that create the fabric of the cornea. Collagen is “woven” throughout the clear front part of the eye that we call the cornea, in a distinct pattern that “cross links” these fibers tightly together. With equal woven patterns across the entire tissue, any force inside or outside the eye is “shared” equally across the entire “fabric.” Rubbing can unlink and stretch out these fibers and appears to damage the cells that normally repair this “fabric.” Triggering the defense system from excessive rubbing can also lead to the release of histamine (responsible for itching) that may lead to a vicious cycle of rubbing (similar to scratching an itch that then itches all the more). As we pour our inflammatory chemicals into the tears bathing our eyes, these can ultimately work against good tear production (and aggravate the corneal cells and fibers further). As the fibers become loose in areas most affected, the resulting weakness in the cornea will result in an outward “bowing” of the cornea - called a “cone.” Instead of the perfect spherical, desired “roundness” of the cornea, any bowing will distort the cornea leading to misshapen images (astigmatism) requiring stronger glasses or contact lenses to reshape the images necessary to good vision. At the extreme, this “cone” shape is called “Keratoconus” and can so distort the images that surgery to replace the cornea (a corneal transplant) or special procedures (to restore corneal cross linking) may be required.
More bad news is that too much pressure applied for too long may permanently damage the optic nerve (connecting the eye with the brain). This type of damage is commonly called glaucoma and if unchecked, can ultimately result in irreversible blindness. How much is “too much” will depend on many factors, including genetic tendencies for this nerve damage, or any pre-existing damage (from glaucoma or other injuries to the nerve). Also, if you watch the video carefully, you may see the outward bulging of the sclera (or white part of the eye) behind the cornea. Inside that area exists the thinnest and most delicate part of the retina. In patients with an already thin retina (often referred to as lattice degeneration), stretching the retina - especially in these already thinned areas - may lead to tears or holes that can progress to a retinal detachment - and require delicate surgeries to repair (or result in blindness if unchecked).
Lastly, I’ll point out that putting fingers or other objects in close proximity to the eyeball elevates the risk of transferring germs, toxins, allergy-producing materials or dirt into contact with the eye itself. A common cause for “pink eye” is the spread of germs or other materials from such contact. Obviously any time we touch our lids with our fingers, we are taking such risks unless we’ve carefully washed and otherwise disinfected them first. Ironically, one of the causes of acutely irritated and red eyes in the wake of the pandemic, is the inadvertent transfer of hand sanitizers from freshly “cleaned” fingers that then gets into the eye from alcohol or other germ-killing residue in the sanitizer (ANYTHING GREAT AT KILLING ANY AND ALL GERMS IS ALSO PRETTY GOOD AT KILLING OFF CELLS ON THE SURFACE OF THE EYES, TOO!).
My personal. experience is that I am also guilty of occasionally “rubbing” my eyes - and although I am generally cautious about hand cleaning and not rubbing excessively, I may have caused myself a case of pink eye in the past. When my eyes itch, my preference is to use antihistamine (anti-allergy) eye drops, a clean, cool compress and only mild wiping when applying lid cleaning products (Zocuwipes and Avenova being my favorites), since common lid germs can also aggravate eyes and lead to dryness and irritation. Hot compresses are also useful when dealing with non-itchy, dry or otherwise irritated eyes and when applying the (Bruder or other) heat mask, I use only the pressure required to keep the heat in contact with the lids (and not forcibly press on the eyes). Strong blinking and forced eye closure (short of grimacing) are likewise useful at expressing the Meibomian oil glands (and doesn’t require firm finger-pressure, as in the above eye rubbing video) - so there are ways to relieve an otherwise tired, itchy or irritable eye without resorting to “the rub!”
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
What’s up when the “sprinkler system” dries up?
While I’ve posted about Autoimmune Dry Eye Diseases (an extensive series starts here: https://www.eyethera.com/blog/sjogrens-disease-autoimmune-dry-eye-part-1) and on degrees of Aqueous Tear Deficiency (ATD, starting with a post on inflammation here: https://www.eyethera.com/blog/segment-10-aampb-what-we-know-about-inflammation ) separately before, I’ve been asked recently about determining causes for severely poor tear volume (common to ATD) when the autoimmune tests are not revealing. Knowing that the worst ATD is often associated with Autoimmune Diseases, it is usual to suspect autoimmunity at work, but sometimes all the testing related to autoimmunity comes back “negative” or “borderline” and we are left wondering what else is going on.
I posted on my favorite test for ATD (as part of a series on dry eye testing) here: https://www.eyethera.com/blog/what-do-dry-eye-tests-mean-part-7-tear-volume-and-how-we-measure-it and I’ve included some of my thoughts on causation in all of these prior posts. This week, I’ll attempt to summarize some of this information and offer some renewed insights.
I often use artistic license in my analogies and apologize in advance to those who can appreciate my oversimplification of complex topics. Having said that, I proceed to do the same here. Recalling that the surface of our eyes are covered in living cells that need support to survive, I point out that tears are the “lifeblood” of that surface. Job number one for their survival is that they must be kept moist and we have two means for that. One is what I like to refer to as the “emergency backup system” or “firehose” - the large tear glands that can pour salty water over our eyes (and often down our cheeks). Being salty water, this tear is not much more than moist support - so we have what I call the “sprinkler system” - the number Two means for support - but this group of cells and glands provide the 24/7 “clear blood” defined by a lot of water, with some salts, proteins and oils added in (a kind of clear-blood-like “salad dressing” - where the watery stuff is covered by a layer of oils that doesn’t “mix” with the water - so can act as an evaporative shield).
The emergency backup “firehose” will draw water from our bodies to the last drop, to make that salty solution, but the sprinklers are very sensitive to our overall level of hydration. If we get a little dry, they get dry and the drier we get, the drier they can get. This was first brought home to me when conducting an early study on clogged oil gland (MGD) treatment, where we had to exclude patients with severe ATD. The cutoff was 6mm on the Schirmer’s test strips and a young nurse who was both a friend and known MGD patient came rushing in from dropping off her kids at school to get screened for a treatment under this protocol. Sadly, her Schirmer’s numbers were around 3 and 4mm - well below the 6 we needed to see. On further discussion, she admitted to having had only a cup (or two) of coffee since rising and was obviously “under hydrated.” I advised she return after consuming a couple of quarts of water and we’d try again. Fortunately, re-testing came in around 8 and 9mm and we were able to proceed with the study treatment.
When I find numbers less than 10mm, I dig deeply into water consumption habits - including the “anti-waters” (things that encourage peeing and dehydration) like caffeine, alcohol and the host of medications that can dry us out. When less than 6mm, it is time to also look harder for sources of inflammation. Autoimmunity is the king (or queen) of inflammation, as it can single out water-producing cells and effectively kill them off - resulting in body-wide damages to tissues and organs dependent on their water production (commonly leading to eye, brain, gut, reproductive and joint issues, among others). Dry mouth, with severe, related dental issues, is common to Sjogren’s (perhaps the leading cause of autoimmune dry eye), so asking about a dry mouth can frequently lead to identifying this cause. Since autoimmunity is still relatively poorly understood, it is hard to know the exact portions of populations affected and likely varies widely through the many nature and nurture variables. Ocular Cicatricial Pemphigoid (OCP) appears to be a relatively uncommon cause of autoimmune dry eye, but since it can only be diagnosed through a biopsy of affected conjunctiva (the membrane on the surface of the white part of the eye), it is probably significantly under-diagnosed. Similarly, Sjogren’s is perhaps best identified by a biopsy (of salivary glands inside the lip area), so since most are not subjected to this level of testing, it is hard to know how many patients might be revealed as “positive” this way. Other autoimmune diseases can affect these water glands. Reactions to some medications can trigger an autoimmune dry eye (as well as affecting the moist membranes throughout the GI tract), called Stevens Johnson Syndrome - but since this can occur at different levels of severity, it can also likely be under-diagnosed (the full blown illness is extraordinary in its ability to inflict damages and usually requires hospitalization - but at that level of presentation it is hard to miss). Graft versus host reactions in those who receive tissue transplants fall into a similar spectrum. In the end, the key is what we can do for these autoimmune-diseased patients and while we are coming up with better protocols all the time, we are still sadly lacking in a definitive treatment plan for many.
Dr. Elizabeth James, a PhD in Medicine and Healthcare, gives a good rundown of causes of dry eyes and dry mouth without having an autoimmune disorder or thyroid problems, here: https://qr.ae/pKzfYt I began an answer to treating dry eye-related inflammation here: https://www.eyethera.com/blog/segment-10-b-when-we-are-at-war-with-ourselves but it is clear that we need to determine “root causes” of inflammation in order to best treat it and I advise working with a good dry eye specialist to help (often in concert with a team that should include your Primary Care Provider and may include Rheumatology, Endocrinology, Gastroenterology - among others as the findings require).
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
More for 2024 (2 new dry eye medications in the pipeline)
Alcon ( a pharmacy that “grew up” with eye care-related pharmaceuticals and has evolved into a major player in the world of dry eye treatments) has been testing a new drop for dry eye care, known so far, as AR-15512 (a “transient receptor potential melastatin 8 (TRPM8) agonist,” for those in the know). This group of compounds can stimulate the nerves responsible for the sensation of cold temperature and appears to regulate the production of tears. Early work with menthol showed it could trigger this response - but even small doses applied to the surface of the eye would cause irritation and it was deemed unlikely to be useful - despite its ability to make eyes tear. Subsequent compounds have been tested and found to be less irritating and more useful in provoking tear production. Early Alcon studies of this medication have been named “Comet” and the most recent Comet 2 and Comet 3 studies have continued to be promising - enough that Alcon aims for its application to the FDA by mid-2024. Stay tuned for more on this! (links about this here: https://www.optometrytimes.com/view/positive-results-reported-from-phase-3-comet-trials-of-alcon-s-ar-15512-for-dry-eye?utm_source=sfmc&utm_medium=email&utm_campaign=01132024_OD_eNL_Dave%20Kading%20CBR%20TD_IKA%20house%20ad&eKey=ZWphY2NvbWFAYW9sLmNvbQ== and https://escholarship.org/content/qt2gz2d8s3/qt2gz2d8s3.pdf?t=qaeax8 )
Last week, I gave a nod to Stuart Therapeutics and their phase 3 studies of a polypeptide they call ST-100 or Vezocolmitide. This week, “Okyo Pharma announced positive safety and efficacy data from its phase 2 trial of OK-101 ophthalmic solution, a lipid-conjugated chemerin peptide agonist designed to reduce pain and inflammation in patients with dry eye disease.” Recalling that peptides are the building-blocks of proteins, and that our bodies are made up of countless proteins, it is perhaps no surprise that any substance that can direct protein production or affect protein pathways can likely influence tears (containing proteins) and the surface of our eyes (also regulated by proteins). This new drug was shown in phase 3 studies to improve the signs and symptoms of dry eye disease. Stay tuned for more on this! (links about this here: https://www.healio.com/news/optometry/20240109/ok101-achieves-dry-eye-disease-sign-symptom-endpoints-in-phase-2-trial#:~:text=1%20min%20read-,OK%2D101%20achieves%20dry%20eye%20disease%20sign%2C%20symptom,endpoints%20in%20phase%202%20trial&text=Okyo%20Pharma%20announced%20positive%20safety,patients%20with%20dry%20eye%20disease. and https://www.optometrytimes.com/view/positive-phase-2-results-of-ok-101-for-dry-eye-disease-revealed-by-okyo-pharma?utm_source=sfmc&utm_medium=email&utm_campaign=01132024_OD_eNL_Dave%20Kading%20CBR%20TD_IKA%20house%20ad&eKey=ZWphY2NvbWFAYW9sLmNvbQ== )
Lastly, in response to numerous concerns raised during 2023 about contaminated eye drop products that caused eye infections and even deaths, the FDA has revised its guidelines. Optometry Times provided the following information: “This revised draft guidance revises guidance of the same name from October 2023, “Quality Considerations for Topical Ophthalmic Drug Products.” Specifically, the revision discusses microbiological considerations related to product sterility for all ophthalmic drug products subject to current good manufacturing practice (CGMP) requirements. It is intended for the prevention of contamination of ophthalmic drug products packaged in multidose containers.1
Quality considerations for ophthalmic drugs such as gels, ointments, creams, and liquid formulations such as solutions, suspensions, and emulsions, intended for topical delivery in and around the eye, are addressed in the revision.” Initial interpretation of earlier guidelines caused some manufacturers to believe the FDA rules did not apply to over the counter products and this revision makes it clear that these current good manufacturing processes apply across the board to prescriptive and OTC products. The expectation is that this should help prevent future eye injuries. A link to the FDA guidelines here: https://www.optometrytimes.com/view/fda-challenges-quality-requirements-for-ophthalmic-drugs-with-revised-draft-guidance?utm_source=sfmc&utm_medium=email&utm_campaign=01132024_OD_eNL_Dave%20Kading%20CBR%20TD_IKA%20house%20ad&eKey=ZWphY2NvbWFAYW9sLmNvbQ==
Some helpful eye drop safety information shared by Rebecca Petris of the Dry Eye Foundation: https://www.dryeyefoundation.org/
Lastly, for tips on keeping your eye drops sterile and safe, this video link was also shared: https://www.eyedropsafety.org/news/blog/preservative-free-eye-drops-how-to-reduce-the-risk-of-bacterial-contamination
Stay safe!
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
What’s new in 2024? Let’s focus on the nerves!
Dompé corneal nerve graphic for Oxervate
Another pipeline first!
Stuart Therapeutics has started a study for dry eye treatment using a novel approach. As you recall from my earlier posting - tears are made of water, salts, proteins and oils (I use the salad dressing analogy here – but it is perhaps more correct to see tears are a form of “clear blood” to nourish, support and protect the surface of the eyes). Most current treatments aim to reduce inflammation by interfering with inflammatory pathways (steroids, cyclosporine, lifitigrast and the like). This supports tear production, but has its most profound effects on tear volume (reducing the damaging effects of inflammation on the water-producing cells). Most include moisturizers and some include oils (Castor oil for Restasis, or the novel, solely artificial oil in Miebo). Cyclosporine also has been found to promote protein production from the mucin-making goblet cells. Salt production is well regulated but becomes unbalanced through evaporative loss of water and resulting toxically-high salt concentration, so adding moisture in artificial tears is a standard strategy.
Stuart Therapeutics new product is a “polypeptide.” Polypeptides are made from strings of amino acids called peptides – which are the building blocks of proteins found throughout nature. Diverse as a group, they are known to help with the many functions required for a healthy life. This new, synthetic group of amino acids they call “PolyCol,” appears to assist in building up or repairing damaged cells within the ocular surface. This includes the nerves beneath the epithelial surface as well as helping restore surface cells. Corneal nerves are the “maestro” that helps coordinate the “symphonic” production of tears from the “orchestra” of cells and glands that make those tears. These nerves are also responsible for the constant upkeep or repair of corneal surface cells – so it is no surprise that other approaches to dry eye includes the repair of those damaged nerves (see my post on related neurostimulation https://www.eyethera.com/blog/what-is-neurostimulation-for-dry-eye-treatment-and-do-i-need-it ).
Dompé is a company marketing a recombinant form of human nerve growth factor (NGF) they call Oxervate, which has been a staple of eyedrop therapy for patients with damaged nerves leading to a condition called “Neurotrophic Keratitis” (or NK). When the maestro is lacking, the tear quality and volume suffer, as do the surface cells maintained by those tears. Chronic “open sores” (ulcers) can form, and corneas deteriorate. Since the nerves are “broken” there can be chronic pain from the remaining swollen “stumps” of those nerves – or the corneas can become “numb” as feeling is lost. Sadly, the higher pain centers can become so overburdened that a chronic pain can exist independent of the state of the surface nerves and cells. See my link to this topic here: https://www.eyethera.com/blog/why-do-my-eyes-hurt-even-though-my-eye-doctor-says-they-look-fine
Current treatments that align with this new product include Autologous Serum Tears, Platelet Rich Plasma drops, Oxervate (as noted above), amnion products and any other forms of “Neuro-Stimulation” as I noted in the earlier post (including Tyrvaya nasal spray and iTear). Adding a new angle that doesn’t require blood draws and frozen storage, or hyper-expensive and often hard-to-dispense drops (Oxervate, with its syringe to meter the drops), blurry “contact lenses” made of human-derived membranes (amnion) or frequent sneezing (Tyrvaya) will be most welcome! It is also true that it sometimes requires a number of these products to turn around these difficult problems - so adding another “arrow to our quiver” of useful therapies is always good news! For a full physician-level discussion of the new product, see this link:
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
Why do my eyes feel tired all the time?
From: https://www.aoa.org/healthy-eyes/eye-and-vision-conditions/computer-vision-syndrome?sso=y
First - Happy New Year! I hope 2024 is the year for great advances in dry eye care - and I want to be a part of that evolution! My contribution on these pages will continue to be my blogging efforts to educate and raise awareness - and in my dry eye specialty practice - my commitment is to continue to offer leading edge technologies and treatments. Today let’s focus on “tired eyes.”
“Tired eyes” is a common complaint among dry eye sufferers. There are several likely reasons for this and I can enumerate a few of them here. I’ll start by reposting an answer I made to a patient with “a little conjunctivochalasis” (CCH) who asked if this could cause tired eyes:
Yes - partly because of the relationship to dry eyes (which increases blink rates - a bit like running a marathon all day), partly due to the poor distribution of the poor tears (causing increased dry eye symptoms - that drain you and also cause eyes to want to close). Dealing successfully with the dry eye problems can sometimes offset the CCH-related fatigue enough, but sometimes it is still necessary to fix the CCH. I have a lot of posts on CCH on my eyethera.com/blog
Blinking is central to eye health and can occur at rates from 2-50 times per minute - as observed in human studies (Monster AW, Chan HC, O'Connor D. Long-term trends in human eye blink rate. Biotelem Patient Monit. 1978;5(4):206-22. PMID: 754827.) Remember that a key motivator to spontaneous, involuntary blinks are the “dry spots” forming on the surface of the eye - and - at a subliminal level - causing irritation to corneal nerves that become exposed by the evaporation of the tear film overlying those nerves (leading to the dry spots). Dried out cells become injured (or dead) and allow them to “stain” with some of the dyes I referenced in my dry eye testing series of blog posts. (See: https://www.eyethera.com/blog/more-on-staining-the-surface-of-a-dry-eye-and-what-it-means) When there is a problem with tear oils (too little or too poor a quality - including those oils tainted with soapy residue from germ byproducts), then the oil’s “liquid Saran Wrap” benefits are lost and the water leaves (evaporation). This means that a lack of good oil will lead to a rapid blink rate (trying to keep up with that evaporation). This in turn, is that “running a marathon” effect that can tire out the blink-muscles and make eyes “feel tired.”
The fine muscle movements required to keep eyes focused and coordinated for the myriad activities we require them to do, make eye muscles the most active muscles in our entire bodies. “Considering that we make at least 100,000 saccades alone each day, it is not surprising that many extraocular muscles are very resistant to fatigue.” (Wong, Agnes M F, 'Eye Rotations, the Extraocular Muscles, and Strabismus Terminology', Eye Movement Disorders (New York, 2008; online edn, Oxford Academic, 12 Nov. 2020), https://doi.org/10.1093/oso/9780195324266.003.0007, accessed 1 Jan. 2024.) Saccades are the back and forth eye swings - that among other things, are the swift movements we use to read text like this. We also have pursuit movements, where we cause our eyes to follow objects around (like tracking traffic while driving). Add to this the blinking and emotive muscle movements of the eyelids and you have an Ironman/Ironwoman-level of activity going on daily for most of us. An interesting treatise on blinking and exercise can be found here: more about blinking (Paśko W, Zadarko E, Krzeszowski T, Przednowek K. Relationship between Eye Blink Frequency and Incremental Exercise among Young Healthy Men. Int J Environ Res Public Health. 2022 Apr 5;19(7):4362. doi: 10.3390/ijerph19074362. PMID: 35410042; PMCID: PMC8998332.)
Another consideration is that when eyes become irritated (as from dryness), their most protective reflex is to close. As eyes dry out, they become progressively irritated and this produces a stronger urge to close (and rest) them. Forced prolonged use of eyes (as is frequent in this digital era) encourages more closures to reduce this level of strain and the closing of eyes is part of sleeping. Fatigue is a strong incentive to sleep and we can equate eye fatigue and this need to close them, as a “tired feeling.” Physical fatigue refers to the muscles getting tired. Mental fatigue has to do with reducing the ability to concentrate. When eyes become constantly irritated from dryness, this constant, annoying “buzz” at higher levels in the brain appears capable of inducing a degree of mental fatigue (and another reason for eyes -and their owners - to “feel tired.”) Following the 20/20/20 rule (see the excellent article by the American Optometric Association: https://www.aoa.org/healthy-eyes/eye-and-vision-conditions/computer-vision-syndrome?sso=y) , getting sufficient sleep and taking care to make the best of tears will help ensure your eyes feel less tired at the end of these increasingly longer days, now that we’ve passed through the 2023 Winter Solstice. Here’s to a great 2024!
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
Happy Holidays and Getting To Know Dr. J
First - Happy Holidays! For people suffering with dry eyes (or any chronic disease), it can sometimes be hard to have your best celebration for any occasion, but many professionals (including me) are working hard to deal better with this (otherwise if untreated) chronic, progressive disease.
Getting to know Dr. J is a video co-produced by (my wife and I’s eldest grandchild) Ladybird Slater for a school project for her college, the University of New Hampshire. I don’t get the chance to discuss dry eye (most will sigh with relief over that), but it does give a glimpse into my past and present life. Hope you like it (we think she did a great job!)!
Getting to know Dr. J
More about CCH (When the eye’s white surface turns to a washboard and tears have an obstacle course…)
I was recently asked how important the fornix is to Conjunctivochalasis (CCH) and should it be restored in CCH surgery.
The “fornix” is the reservoir or “well” that contains our best tears, in that those tears have yet to be used for supporting the exposed surface of the eye. The exposed tear is becoming the old, used-up, dried up, dirty tear that needs to be replaced and a blink is that “heartbeat” that renews that support by turning over that tear. So preserving the fornix is important. (We want a deep well, capable of holding a lot of healthy, fresh tears.)
Some technologies that excessively burn and damage the conjunctival tissue that has come loose and otherwise “rides up” (shortening the fornix) can risk “over-tightening” and foreshortening the reservoir (shortening the depth of the “well.”) Higher levels of heat, applied in broad swaths, can cut, burn and scar down that membrane. In my experience, radio frequency can straddle the line between tightening and over tightening - and can seal the conjunctiva over the white of the eye (sclera) without damaging the reservoir function. The lighter degrees of heat can be applied in serial, linear passes - sequentially shrinking and “shrink wrapping” that membrane - with just enough of a “burn” in places as to heal and “stick” the membrane back in place.
Excess burning causes higher levels of scarring and tightening, which may, for some patients, risk significantly reducing that fornix. An alternative is cutting away the excess conjunctiva and either allowing it to then heal - or gluing amnion over the exposed white tissue (sclera). Either can restore the fornix but doesn’t fix the problem (MGD and evaporative dry eye) causing the problem (CCH).
Off-label use of RF as described in my studies, has been shown to improve MG function, so combining both the RF plication (shrink wrapping the membrane) with the RF -heated expression of wax-clogged glands has made more sense to me. There are some relative contraindications to RF (an active cardiac pacemaker being one), so there are times where I’ll turn to alternative methods.
Some of my posts relating to CCH, including this most recent post here:
https://www.eyethera.com/blog/can-conjunctivochalasis-get-better-without-surgery
And my earlier series on CCH - part 3: When do we treat CCH – and what are the non-surgical options?
Jun 12
Written By Dr. Edward Jaccoma, MD
https://www.eyethera.com/blog/cch-part-3-when-do-we-treat-cch-and-what-are-the-options
Conjunctival Chalasis (CCH) part 2 - How do we fix it?
Jun 5
Written By Dr. Edward Jaccoma, MD
https://www.eyethera.com/blog/conjunctival-chalasis-cch-part-2-how-do-we-fix-it
What is Conjunctival Chalasis (CCH) and why should I care?
May 29
Written By Dr. Edward Jaccoma, MD
https://www.eyethera.com/blog/what-is-conjunctival-chalasis-cch-and-why-should-i-care
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
Eyedrops and Glaucoma - a new study supports clinical observations
Antihypertensive Eyedrops Trigger Dry Eye Disease, Corneal Damage
September 19, 2023
https://www.ophthalmologyadvisor.com/topics/cornea-ocular-surface/antihypertensive-eyedrops-trigger-dry-eye-disease-corneal-damage/
This study supports the common clinical findings many dry eye doctors see in their clinics on a daily basis - and which have been demonstrated and validated by earlier studies. THE LAST THING I WANT TO DO IS BASH THE USE OF DROPS TO CONTROL GLAUCOMA. I’ve published on this before https://www.eyethera.com/blog/jwk8lv0558b5ewcp7cxummr7pusblv and https://www.eyethera.com/blog/dry-eye-cataract-and-glaucoma-segment
I think it is important when studies like this are published, to point out that glaucoma is a potentially blinding disease and that dry eye is much less likely to result in blindness. Job number one is to prevent blindness and I routinely prescribe drops to treat glaucoma. Fortunately, SLT (laser) and Durysta implants are often a good way to avoid glaucoma medication and when we have to turn to drops, increasing numbers of “preservative free” drops are now available to reduce the negative impact of these drops. Various operations exist to also reduce dependence on drops (It was interesting to read in this same study, that substituting surgery for drops did not significantly reduce the dry eye impact - but this might be predicted knowing that surgery promotes inflammation as part of the healing process and requires frequent use of topical steroids, antibiotics and other medications that fight inflammation at the expense of adding preservatives and other chemicals to the surface of that operated eye).
I find that many glaucoma patients received relief from the burden added by glaucoma drops, by increasing the amount and quality of their tears, using the protocols I’ve commonly used for that purpose. It makes sense to me that patients with robust surface health - largely thanks to having excellent tears - will tolerate their glaucoma drops better than those who have poor quality tears and an already disrupted, damaged ocular surface. I would urge any patients who require daily topical medication (like glaucoma patients on glaucoma drops) to get a good dry eye evaluation and institute any recommended treatment at the same time they begin their eyedrop treatments.
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
Why do my eyes hurt - even though my eye doctor says they look fine?
This is a fairly common question I hear in my dry eye center, and the answer can be complex. No one answer fits all eyes or all eye pain, but the usual name given to this group of complaints is “pain without stain,” implying the eye looks normal, so there is no obvious cause to the pain described by the patient.
A few weeks ago I posted about “pain without stain” here: https://www.eyethera.com/blog/testing-part-8-miscellaneous-testing-the-good-the-bad-and-the-ugly-side-of-testing As I mentioned, this opens the door to a portion of dry eye patients with complex problems that are often overlooked or passed over, as our ability to effectively detect, diagnose, and treat this problem remain limited. Treating pain is an important part of a doctor’s duty and dry eye doctors are constantly looking for better tools to fill this toolbox.
One increasingly off-label utilized medication is Naltrexone – in the news as an emergency rescue drug for those who overdose on opioids like Fentanyl. Due to the complex nature of how our bodies deal with pain, we have our own versions of opioids - and the receptors for these innate chemicals exist in nerves and tissues occurring throughout our body.
In numerous prior posts, I’ve covered the role of irritation from dryness activating our natural defense (immune) system, leading to inflammation and initiating the “viscous cycle of dry eye disease.” Corneal nerves become damaged and abnormal – which can lead to chronic pain. Treating the dry eye can reduce irritation, but in some cases the damage to the nerves appears to be too great and the pain lingers. Low Dose Naltrexone (LDN) has been shown to reduce inflammation and has been helpful in curbing pain in a number of chronic, painful conditions such as fibromyalgia and MS. Recent research has shown that LDN eye drops appeared to improve tear production in rats who were made diabetic, with related diabetic dry eye disease, so there may be a number of benefits to the way this drug can reduce inflammation. Zagon IS, Klocek MS, Sassani JW, McLaughlin PJ. Dry eye reversal and corneal sensation restoration with topical naltrexone in diabetes mellitus. Arch Ophthalmol. 2009 Nov;127(11):1468-73. doi: 10.1001/archophthalmol.2009.270. PMID: 19901212; PMCID: PMC2840396.
In a recent post from Glance By Eyes On Eyecare https://glance.eyesoneyecare.com/ a new product for neuropathic corneal pain was announced as under investigation. The following is an excerpt from a physician-level communication I received from them:
“Are there any new treatments for neuropathic pain?
OKYO Pharma Limited announced it has submitted an investigational new drug (IND) application for the development of OK-101 to treat neuropathic corneal pain (NCP).
What is OK-101?
OK-101 is a lipid-conjugated chemerin peptide antagonist of the ChemR23 G-protein coupled receptor, which is typically found on immune cells of the eye and is responsible for the inflammatory response.
How does it work?
OK-101 was developed using a membrane-anchored-peptide (MAP) technology and has been shown to produce anti-inflammatory and pain-reducing activities in mouse models of DED and NCP.
Didn’t OKYO already file an IND for OK-101?
Good memory! And yes—back in November 2022. However, this IND was for DED, not NCP.
As for updates on that application… in April 2023, the company activated the first U.S. clinical trial site for its first-in-human (FIH) phase 2 multi-center, placebo-controlled trial of OK-101 for DED, which was followed by randomized dosing of participants in June 2023.
How about for NCP?
According to the company, preclinical data from a ciliary nerve ligation model on mice found that OK-101 reduced NCP response similar to that of gabapentin (a common oral drug used for such pain), administered via intraperitoneal injection.
The model supported the topical administration of OK-101 as a potential non-opioid analgesic for NCP.
Gotcha. So what’s next?
Pending FDA acceptance, the company—in partnership with Boston-based Tufts Medical Center—is planning to launch an open-label phase 2 study in Q1 2024, with an anticipated 40 patients to be enrolled.
And the significance of this?
With no current FDA-approved drug on the market to treat NCP, this second indication for OK-101 could become the first, proving to be a game changer for patients suffering from this chronic condition.”
I should add that I don’t have any “insider knowledge” about OK-101, but I’d guess that it comes out of the research-information obtained from studying the natural opioids in humans (also known as endorphins, enkephalins and dynorphin-related “natural painkillers”). I welcome any additional tools to this important toolbox as current approaches remain all to limited!
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
Even Dry Eye Specialists get the Blues.
As a mentor to other dry eye doctors, I am sometimes asked why certain treatments “fail” to improve their patients. Even dry eye specialists can get confused (and depressed) when their best efforts fail to help their patients, and since this question is relevant to that issue, I thought I’d post one of my recent answers.
The question I answered went something like this (paraphrased): “I’ve used frozen, preserved amnion contact lenses (Prokera) to treat a good number of patients with SPK, only to find they continue to have SPK – what am I doing wrong?” The doctor went on to detail some of the dry eye treatments used for these patients, including night ointments and nighttime patching, lots of artificial tears, cyclosporine or lifitegrast, Tyrvaya (the nasal spray that stimulates tear production), lotemax (a topical steroid) for flares and home therapies or Low Level Light Therapy (LLLT) to manage the Meibomian Gland Dysfunction (MGD).
One treatment I discussed in an earlier blog referred to using Amnion membranes to help heal damaged eye surfaces (see here: https://www.eyethera.com/blog/what-to-do-when-the-surface-of-your-eye-gets-broken-scratched-operated-on-infected-or-otherwise-damaged ) - which applies to the Prokera referenced in the question above. Amnion is the tissue surrounding a baby growing in a mother’s womb, and the influence it has on the baby is both nourishing and generally supportive of helping the baby grow quickly and healthfully in that womb. As such, I’ve referred to using these membranes as a means of “putting the eye back in the womb” to help heal surface damage.
https://biotissue.com/products/ocular/prokera/#prokera-form Image of the popular “Prokera Slim.”
Superficial Punctate Keratopathy, or “SPK” is the common finding in many types of eye-surface diseases (and refers to groups of damaged cells on the surface of the eye which are best seen using a microscope and fluorescein dye - see photo)
The photo was taken through the eyepiece of an examination microscope using an iPhone camera after applying a drop of fluorescein dye and using a blue filter. This patient has a geographic area of “torrid SPK” on the illuminated cornea, that looks a bit like a leaning chess rook, with some patchy, more typical SPK to the right of that “rook.” Looking further, we can see a small “divot” or “notch” in the margin of the lower eyelid, which is a common finding following the healing from a stye (this patient had a long history of them). We also see a little “foam” in the pit of that notch (indicating bacterial activity leading to inflammation of the lid and eye). Harder to appreciate in this blue-light image are blood vessels crossing the margin of the lower lid (squiggly lines) and dilated blood vessels on the white of the eye – all indicating degrees of inflammation – in this case a combination of evaporative dry eye disease, rosacea and related blepharitis (irritated eyelids).
- but the main cause remains dry eye disease, which is a many-faceted beast. Anti-inflammatory medications including Cyclosporin (Restasis, Cequa, etc), Lifitigrast (Xiidra) and steroids (like Loteprednol) are used to treat dry eyes because they are good at reducing Aqueous Tear Deficiency (ATD = too little water being produced) but are not great at improving evaporative dry eye from Meibomian Gland Dysfunction (MGD). In my practice and in large clinical studies, MGD is the leading cause of dry eye, though it can couple with ATD. Prokera is great for giving a jump start on healing a dry eye-damaged surface, but unless you deal with all the ancillary, co-contributing issues, the SPK is likely to be only partially improved or to recur quickly. LLLT can help some MGD, but as most MGD is obstructive and most obstructions involve waxy plugs, unless you are clearing these plugs (and a substantially heated expression appears the best way to do it), then you're not going to get very far.
Apart from waxy plugs (common in early stages of MGD), there are scarring issues (well described by Dr. Steven Maskin) that can begin as "periductal fibrosis." This can require probing to make good headway. Rosacea is a common cause of the non-obstructive versions of MGD and here, IPL (Intense Pulsed Light – see my earliest posts on this here: https://www.eyethera.com/blog/not-so-secret-weapon-of-dry-eye-treatment-intense-pulsed-light-or-ipl ) can really shine (and LLLT may play a positive role). Getting appropriate degrees of buy-in from patients, in doing required levels of "homework," is always key to anything else (including Prokeras) you can offer. You mentioned home therapies - I include oral Omegas 3-6-9 capsules, Heat masks and lid crunches (unless the primary issue is Rosacea), and lid hygiene products (HOCL and a cleanser like Zocuwipes or Cliradex products).
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