ARVO Monday morning: Dry Eye I
This is why I love ARVO.
You go to another conference, and any “dry eye” session with the number 1 on it is going to be running along some fairly familiar themes. All good, just not, you know, new, fascinating, or all that sophisticated. They’re also more likely to have a commercial flavor.
At ARVO, dry eye, or any disease really, is a different animal. The Dry Eye 1 session here was a collection of really exciting cutting edge presentations.
On benzalkonium chloride (BAK)
If you follow my stuff in general, you’re already bracing yourself for my soapbox as soon as you see the acronym for this ubiquitous preservative.
The first speaker in the dry eye lineup:
“An optimized model of dry eye disease using benzalkonium chloride in C57BL/6 mice: effects on the ocular surface”
Richard Zhang (University of New South Wales)
Lurking under the fancy presentation titles and the animal research that may seem so far removed from our everyday lives, there is often something surprisingly relevant. The context for Dr Zhang’s presentation is actually how they use BAK to cause dry eye in mice for medical studies. Yes, you read that correctly. It’s a complicated world out there in research and this kind of thing reminds me of when, long ago when I was advocating for people with complications like RCE after laser eye surgeries, I first came across the use of PRK to induce RCE in mice. Sigh. Anyway.
Dr Zhang talked about how, while we know BAK causes dry eye, we don’t actually know very much about how and why, and this is what he explored. His research debunked some assumptions and was aimed at narrowing down how much BAK, applied how often, can reliably cause dry eye specifically, as opposed to other types of damage, and they discovered some other interesting things along the way.
There was one series of photos in particular that struck me. It showed the progressive effects of very low concentrations (lower than they would use for the “let’s give mice dry eye” purposes) in cultured limbal epithelial stem cells. At 0.01%, on a picture with some sparse signs of life, there was a comment like “They weren’t all dead right away”. If I understood correctly, they showed that a single exposure at 0.01% was enough to induce cell necrosis. On those same cells in vivo, though, they weren’t seeing the same effect and don’t know why.
But we’re talking about research on only days’ worth of exposure. 0.01% BAK is actually the concentration of BAK that is in >20 over-the counter eye medications such as Zaditor and Lumify, as well as even some artificial tears, like two of Bausch & Lomb’s. I’m trying to meet with Dr Zhang later today to learn more.
Can meibomian glands be regenerated from atrophy?
Whew - talk about a hot topic for our dry eye world!
“Meibomian Gland (MG) Acinar Regeneration from Atrophy in a Fgfr2 Conditional Knockout Mouse Model”
Lixing Reneker (University of Missouri)
Fun fact: While we know MGD is a big cause of dry eye, MGD is much more prevalent amongst Asians (42-68%) than Caucasians (4-31%).
Dr Reneker started with some excellent context on how MGD works - the different types (obstruction vs change in quality/quantity of meibum) and also how little is really known about the underlying causes. I really enjoyed the graphics and explanations of how those glands work - she walked us through the life cycle of a cell all the way to when it disintegrates and turns into the stuff our glands are meant to secrete.
So the question is: Are our meibomian glands capable of repair and regeneration?
The answer, based on their research of inducing severe atrophy in various ways and following the progress over time, is: YES, meibomian glands absolutely are capable of acinar tissue repair, regrowth and regeneration, but it depends on whether the ductal structures have remained intact.
All in all, very encouraging research! I know this is a big ‘mystery’ area for patients, and a frustrating area for those who have visited multiple doctors, because they are so likely to receive conflicting answers about both their diagnosis and their prognosis.
So to me, the take-home message is, just because you’ve been told you have gland atrophy… doesn’t necessarily mean there’s no hope of MG recovery, depending on specifics, but please don’t blame your doctor if you’re not getting what seem to be straightforward or consistent answers, because there’s so much more that science hasn’t figured out yet.
Of mice and mice
“Increased conjunctival monocyte/macrophage antigen presenting cells in Pinkie RXRα deficient mice with accelerated dry eye”
Stephen Pflugfelder (Baylor)
I know several of you have visited Dr Pflugfelder or his colleagues at Baylor somewhere in the course of your dry eye journeys!
This is one of the ones that went “whoosh” right over my head, except for the part about retinoids being essential for ocular surface health, and the predictable question from David Sullivan afterwards about how we reconcile that with the fact that retinoids (his words) “literally make the meibomian glands run away screaming”.
Does Vitamin D play a role in dry eye?
“Characterization of Vitamin D Levels in Ocular Surface Tissues and their Association with Dry Eye Disease”
Ashley Bascom, U of Houston School of Optometry
This research presented how they identified active Vitamin D in the tear film for the first time, and showed that it was significantly decreased in dry eye patients. They hypothesize that it may play a role in the inflammatory component of dry eye. There were interesting responses and questions afterwards, including whether the prevalent vitamin D deficiencies may be contributing.
Blah blah blah blah DRY EYE blah blah blah
There was another presentation that made my eyes cross. I am sure it must have been amazing, both because it happened here, and because the research came from Schepens (Harvard)… I just don’t know what it MEANS.
High fat diet messing with lacrimal glands?
“High fat diet induced functional and pathological changes in lacrimal gland”
Xin He (Xiamen University)
Back to the immediately practical world (maybe). Obesity, high fat diets and what, if anything, this means for dry eye - in this presentation, limited to the lacrimal gland function.
In this research, they looked at both whether a high fat diet impairs the meibomian glands, and whether it was reversible (yes and yes).
Dr He first walked us through the process whereby a high fat diet leads to, progressively: lipid accumulation, oxidative stress injury and inflammation, proliferation, apoptosis, and finally lacrimal gland dysfunction.
Then they looked at reversal - did the lacrimal glands return to normal when the mice were returned back to a standard diet? Only in part, but inflammation was reduced. After that they looked again at another approach to the diet change (standard diet plus fenofibrate) and in that case they were able to complete reverse the pathological changes in the LGs.
Lots of audience questions including role of sex (they only studied males) and whether they checked for indirect effect of systemic parameters (no).
Note: In a later session there is a presentation on the impact of a high fat diet on MEIBOMIAN glands.
And one more
Function of lacrimal gland myoepithelial cells in homeostasis, aging and disease
I was running on overload at this point. The part I enjoyed most (and judging from the oohs and aahs, I was not alone!) was some amazing color videography of expansion and contraction of myoepithelial cells, and how inflammation impairs the contractions. Very cool stuff.
Got dry eye? Why you should take heart:
There may, or there may not, be anything that is presented at this conference, or anything that I happen to blog about, that you feel is directly relevant to you personally. But there’s still a broader theme of good news that matters for all of us.
The numbers of PEOPLE involved in dry eye research at all levels just takes my breath away, and it is underscored in this environment. For every 15 minute presentation, we see long lists of names and pictures of teams involved, and the nature of a lot of the research is resource-intensive . The packed rooms and the discussions and debates further reveal the level of commitment to this disease area.
We have so many reasons to take heart and to know that scientific breakthroughs are happening and will continue to happen in the dry eye space.