ARVO 2019: Final impressions and conclusions

“From bench to bedside and back”…

That’s the slogan for ARVO 2019.

ARVO participants and attendees… if any of you ever see this… please consider sharing your “bench to bedside” stories with us patients!

Even though I go to quite a few medical conferences, ARVO is completely different. At ARVO I found myself overwhelmed with the sense of how much is going into research - eye research in general, and dry eye research in particular. Every time a presenter showed that last slide with the picture of their team and all the people who were part of their research, I just found myself once again in awe of how much is going into these efforts.

As consumers - patients - people, we really don’t have any idea at all of what it takes for new treatments - new drugs, in particular - to be developed. People with highly symptomatic dry eye disease only know that they are in pain and that nothing is helping enough. We have no way of knowing what it may have taken for a single therapeutic to come to market - the years of early research, the struggles for funding, the regulatory hurdles, the financing and marketing side. We only know our own stories. (If you’re interested, you can read about those at dryeyestories.com.) But learning the reality of what goes into dry eye research could make a huge difference to our community in terms of bringing us hope for better futures.

I want to ask YOU - you the researchers, you the clinicians, you the biotechs and pharmaceuticals and regulatory bodies - to tell us YOUR stories.

What have YOU put into dry eye solutions? What does your work mean to YOU? We would love to hear from you.

ARVO 2019 participants, if you’re interested in sharing your stories, please contact Aidan. We would love to be able to share these stories with patients.

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Progress is all about the CONVERSATIONS.

Conversations… this word has been quietly reverberating in my head for months now. And at ARVO 2019, one of the strongest impressions I came away with is that everything of value that is happening, is happening as a result of conversations.

In that enormous convention center, everywhere you went, it was buzzing with conversations. All the seating areas - and I just love how well designed the Vancouver convention center was for this - were packed with people talking to each other about their research projects. The scientific posters - jammed with people having conversations with each other about their research. The presentations - all provoking more and more conversations. The side meetings and dinners and other events - it’s all about the conversations amongst people whose interests coincide, whose observations and opinions collide, whose ideas are constantly mutually impregnating each other.

In the dry eye world, conversation is constant, though so much more active and obvious and intense at ARVO. It was like watching the tribble effect right before your eyes.

These conversations about research, problem-solving and solution-seeking… these conversations are all amongst researchers and clinicians, and the industry and of course regulatory bodies.

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What about US? How can we, the patients, become part of this conversation?

This is why I started The Dry Eye Foundation - after all these years of running the Dry Eye Zone, Dry Eye Shop, etc.

It’s because we patients need to have a different role in the world of answers and solutions than the relatively negligible role we have now as consumers of healthcare services and products.

Getting the Foundation off the ground has been a slower process than I expected when we first incorporated in late 2018. And not for technical reasons. We got our 501(c)(3) status in late February. I’m the bottleneck. We haven’t even finished recruiting our board of directors yet, and I’m the one that’s holding it up. Why? I found that I’ve had to take it slow. I’ve had to find pockets of time here and there to just ponder, to continue to let ideas percolate, and let the vision take clearer shape, lest I fall into the trap of rushing to do stuff just because stuff needs doing and there are ready hands or even ready money to do them.

Heaven knows there’s so much STUFF for a dry eye nonprofit to do! There are so many needs. There will always be more to do. Patient education, assistance funds, meetings, support groups, research projects, handbooks, and a ton of other things.

But I don’t want to just “do stuff”. I want the process of finding solutions to change.

And I am convinced the key lies in the conversations.

We patients are big data.

When, and how, and where will we patients find our collective voices?

Researchers are all about data, you know, and… we ARE data. We are BIG data. Our experiences, our symptom patterns, our treatment histories, our environments, our genetics. Not to mention our opinions about what matters in dry eye research. WE ought to be influencing dry eye research, from bench to bedside and back.

How will we, as a community, uncover and collect and analyze and understand and package and communicate the vital data and insights and opinions that WE can uniquely bring to the table in order for true solutions to emerge that will improve life for people with dry eye disease?

This is a core part of my vision for The Dry Eye Foundation. If you want to be involved, speak up.

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Thank you, ARVO 2019!

For me, this year, this conference was exactly the right thing at the right time. From soaking in the big picture of it all, to learning from presentations and posters, from reconnecting with doctor friends I haven’t seen in a long time to meeting many wonderful doctors and researchers for the first time, it’s been a joy beginning to end for me personally. ARVO 2019 organizers, you are really something!

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And thank you, sponsors!

Everyone who contributed to my GoFundMe travel fund for ARVO and ASCRS… I am more grateful than I can possibly express. I know crowdfunding has been around for a long time now, but personally, I’m new to it. I hope that the feeling you get when people you don’t even know want to support what you’re doing never grows stale.

After 15 years of pondering and researching and writing about dry eye mostly on my own time and dime, it’s a joy to have more ways to feel more connected to more people in the process. So again, thank you all!

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By the way…

Vancouver is incredibly beautiful.

How did I not know this? I mean, I only live a few hours away.

But I’ve never spent any time in downtown Vancouver before, and I had no idea. It helps, of course, that we had stunningly beautiful weather the entire time, and that the convention center is designed to showcase the environment, to make you feel that you are outdoors. But everyone around me who had never been here was echoing the same feeling of amazement at the beautiful surroundings.

ARVO Tuesday morning - Dry Eye II and The Lacrimal Gland

Dry Eye II

This session, as I scanned down the presentation titles, looked to be, easily, the least relatable of everything I have experienced at ARVO.

And yet even here, lurking under the unintelligible, unpronounceable, impenetrable depths of lab science, are glimpses into an entire world of work that comprises all the precursors to so much that we want to know and see in our dry eye world.

For example, the technicalities of “Silk-Derived Protein-4 (SDP-4) Inhibits Nuclear Factor Kappa B (NF-κB) Inflammatory Signaling that Underlies Dry Eye Disease (DED)”, as a presentation, might not quite set your pulses racing, yet what do I read about in the dry eye Facebook groups every single day? “Doctors just keep giving us stuff to treat our symptoms. We want to get at the underlying causes!” Well, guess what. Here is where the science happens that tries to get at causes. We have no idea how many people are wrestling with these questions, really.

Or, “Anti-inflammatory properties of butyrate on the ocular surface epithelium”. Another popular theme in dry eye social media is holistic medicine, diet, and how our eyes are tied to our general health. The context for this presentation was microbial imbalance in the gut due to things like aging and antibiotic treatment, and it was about butyrate, which they believe has anti-inflammatory properties on the eye surface, but originates in the gut.

Another presentation got into dizzying depths of detail on Lifitegrast (a/k/a Xiidra), and another was about testing of a drug for Sjogrens, and two others were on yet more approaches to reducing damage to cells in the eye that contribute to dry eye.

The Lowly Lacrimal Gland

“Lacrimal gland biology in homeostasis, disease, and repair - Minisymposium”

My memory of the last scientific session I was able to attend at ARVO was that it was really fun. Perhaps it’s because I’m suffering from a bit of meibomian gland exhaustion. So much of the dry eye world talks of nothing else these days. I used to worry about patients walking into a doctor’s office and being seen and spoken to as if they were a pair of disembodied eyeballs. (We really are more than a bunch of ocular surface structures flying in formation.) These days I worry even more about patients walking into a doctor’s office and being seen and spoken to as if they were a set of disembodied meibomian glands.

So I was delighted to get to focus on the lacrimal gland. A day and a half after this session, though, I could make very little of my enthusiastic and unfortunately hand-written notes. It seemed really exciting while it was happening. I just can’t always tap my inner nerd on demand after the fact, apparently. But here are a few highlights:

THEY were loving it. That’s probably why it was so much fun to be at. They said it was the first time in 30 years that they’ve had a session devoted entirely to the lacrimal gland and they were all just thrilled that it was happening. The session was actually not very well attended but whoever wasn’t there was missing out.

Darlene Dartt from Schepens (Harvard) gave a truly wonderful overview of the lacrimal gland mechanism - from the greater context of exocrine glands to the bitty details of which cell types wear which hats to get the jobs done. I got a little lost somewhere between the neural regulatory process and the thrombospondin, but that’s to be expected.

Kazuo Tsubota (Keio University, Tokyo) presented on the science of tearing. Dr Tsubota can probably best be described as simply the world’s foremost authority on dry eye. He’s also a delightful presenter, both personally and in his over-the-top amazing 3D videographics of what’s going on in the brain. He started by discussing the inverse relationship between happiness and dry eye (= more dry eye, less happy, and the reverse).

So they asked the question, are tears different depending whether you are happy or not? And as with all tear research, it seems to start with creating “a mouse model”, i.e. simulating the thing you’re trying to test, in mice. How do you make mice happy or sad so that you can test their tears? They tried to make happy mice by giving them friends, toys and lots of room to play. Based on the video shown us, yes, I can personally attest to the fact that they sure looked awfully happy! Sad mice, sadly, were basically stuffed into tubs where they were alone and couldn’t move. Unhappy is the least of how I would describe them. But the fascinating thing that they found is that when they subjected all the mice’s tears to environmental stress (e.g. wind), the eyes of the happy and unhappy mice were affected differently by the very same environmental stress. In other words, there was a brain-mediated response… which brought them to formulate the real question driving their research: “How does happiness affect tearing?” Then we learn about how the superior salivatory nucleus (SSN) control the lacrimal glands, and their research trying to pin down which part of the brain controls the SSN.

Long story short, 170 different parts of the brain - or, as Dr Tsubota puts it, “A whole lot of grey area!” control the SSN, but different parts of it control tears than control saliva. Somewhere in there was something cool called DREADDs, but anyway.

Part of my take-home… I stand in ever greater awe of the incredible sophistication of the tear system, and how much science has yet to learn. (When you consider that the tear system is an essential part of the visual system, the complexity makes more sense.) Next time you see a dry eye doctor and find yourself frustrated with the lack of progress, think of this and cut them a little more slack than you might otherwise.

Next, Austin Mircheff’s presentation was all way, way over my head but gave interesting glimpses into underlying causes of dry eye… and a really interesting research approach. Apparently having carried a pregnancy to term increases Sjogrens Syndrome risk as much as twofold; and pregnancy increases the risk of dry eye without Sjogrens. So they asked the question: Does pregnancy influence gene expression? - believing that it should be possible to develop a preventive mechanism if you can get at the way this develops. The research presented was focused on two things then - environmental impact, and pregnancy impact.

After that, Sarah Hamm-Alvarez on tear biomarkers for Sjogrens syndrome. Did you know that Sjogrens is the second most common auto-immune disease in the US, but it still takes 4 years to diagnosis (down from 6 not all that long ago, though, which is good)? We are lacking in simple diagnostic tests for it and also specific treatments for it.

Dr Hirayama presented on advances in lacrimal gland organ regeneration. That’s such an exciting word. They described two different ways to go about it: (1) replace the organ with a fully functioning 3D bioengineered organ created from cells in vitro (demonstrated this with time lapse photography… I remember seeing something like this about meibomian glands at the TFOS meeting a few years back). Or (2) direct cell conversion to target cells. However they do it, it’s just so exciting that this is being worked on.

Dr Makarenkova wrapped up the session on implications of new research on lacrimal gland stem cells. Most of this was way beyond my reach but what I jotted down was that despite the lacrimal glands having plenty of regenerative potential, chronically inflamed lacrimal glands just don’t want to heal.

All in all, this was a wonderfully nerdy session, humanized by Dr Tsubota’s happy mice.

ARVO Tuesday posters

From beagles to boxers

There is so much excitement and buzz around the scientific posters. A ton of fun.

One of the things I found myself noticing while strolling through the poster aisles Tuesday morning was… it’s a bit of a zoo. So many animals on these posters. In dry eye, most of the experiments are done on mice. But Tuesday, I saw rabbits, pigs, tree shrews and even chickens as well. Thankfully for my sanity, not all animal mentions were about animal experimentation. There were quite a lot of dog studies, mostly about canine glaucoma.

A poster about boxers caught my eye - because I had just been looking at one about beagles. But this was about the sport, not the dogs. They wanted to look at contact sports and how they might relate to dry eye, and chose boxers, looking at differences in the tear film of boxers with a history of traumatic brain injuries. You get the picture. It’s fascinating to me how all these researchers come up with the questions that they decide they want to find the answers to.

Sorry I don’t have visuals to share. But just to give you an idea…. You probably know what a big exhibit hall floor is like. Overwhelming: a gajillion booths all vying for your attention as the most relevant, exciting content. That’s what it will be like when I get to ASCRS in a couple of days.

At ARVO, it’s a completely different beast. The enormous hall is dominated by huge sections at both ends devoted entirely to scientific posters. All of the exhibitor booths - relatively small in number, and all related to research in some way or another - are squished into the middle section.

This reflects perfectly how different ARVO is from other medical events. It’s dominated by scientific research, beginning to end. Everything that isn’t about science itself is about funding science and facilitating science and equipping science and supporting science and publishing science and, most of all, connecting scientists.

Silk?

I came across four different mentions of silk in relation to the cornea… one was in a presentation, and the other 3 were posters. They were mostly about healing the cornea surface.

Limbal stem cell deficiency

Every now and then I’ll come across an abstract that focuses on finding practical low-cost ways to bring much needed therapies to the people who need them most. I love these. This is what it’s all about… how do you help the real people? There was one like that at GSLS about scleral lenses in some developing countries..

Anyway, the one that prompted this reflection was an abstract about a lost cost process by which small labs can do work that is compliant with regulatory authorities… specifically for LSCD.

Lipids and lipids

Apparently not all lipids are created equal. A tree shrew study looked at which lipids, specifically, are most responsible for tear evaporation.

Speaking of tear evaporation

Another study looked at the dynamics of tear evaporation and pointed out some assumptions often made that may be wrong. They studied how tear evaporation happens… because evaporation is NOT evenly distributed across the entire tear ilm.

Then there were two more posters digging into specifics of how tear film break-up happens. And, can proteins reduce evaporation? And another with molecular dynamic simulations to model the lipid layer. It just goes on and on. So cool.

Plugs and biofilm

I vaguely remember blogging about a study published about this not long ago by the same authors so I imagine it was from the same research (comparing biofilm on three plug brands).

Parkinsons

I wrote on Monday about biomarkers for Alzheimers… one of the posters Tuesday looked into tear film biomarkers for Parkinsons. Tear film biomarkers were a big theme in general in dry eye research presented at ARVO.

About those tear drains

There was a really nice poster that drew attention to the too-frequent failure to correctly diagnose epiphora (i.e. tears spilling down your face) when it’s related to duct obstruction. I particularly appreciated how they highlighted the impact it has on quality of life even if it’s not considered a major “thing” medically speaking. They proposed a quick and non-invasive way to check for it (strip meniscometry).

Another poster had results of 39 patients who underwent DCR - it showed how their tear dynamics changed afterwards and how the tear clearance decreased. DCR is the surgery you might get if you have chronically obstructed tear drains (puncti). I’ve heard anecdotally from people for years talking about how this made their symptoms worse in cases.

Preserved versus preservative free eye drops

A poster from the University of Navarra (Spain) discussed preserved versus unpreserved glaucoma medications. A high percentage of glaucoma patients have dry eye symptoms. Their findings were that it doesn’t initially appear to be due to a decrease of goblet cells or mucin production but rather an increase in mucus genes in response to damage, possibly due to inflammatory response

Lots of Ls

Saw one poster each on Lubricin and Lacritin. Hope they get moved along efficiently… we need new therapeutics to get to market.

Too many posters to count that were dealing with harvesting, processing, storage etc of limbal stem cells and other biologics for therapeutic uses.

ARVO Monday posters

Of substance versus trivia

I’ve been meaning to say, just for perspective… I know that a lot of what I write about is puzzling to many people who see it - as in, “How could this ridiculously technical or trivial piece of information be in any way relevant to my life?” The answer is, it isn’t, which means if you follow my stuff at all, you are probably doing a lot of skimming. I could, of course, cater for the lowest common denominator. Except that I can’t, because I delight in all levels of information, and because every now and then I get a message from someone that I just happened to have just the right piece of information for them at the right time, and that motivates me to carry on with perhaps an unusual smorgasbord of the technical and the simple, the mundane and the interesting, the broadly applicable and the narrower-than-narrow.

Dr. YouTube

I really enjoy just cruising the poster acreage. It’s a bit hard on the feet, thanks to a concrete floor that goes on forever and ever. But you just never know what interesting things you may come across before you get to the cornea nerd center. Today, the first row or two were all about eye trauma. It’s sad to see posters on things like child abuse (or “non-accidental injury” as the phrasing may go). And gun violence.

Time was a little more limited this afternoon, though, so I was cruising along pretty quickly when I came across a fun little a poster about a study assessing the reliability of YouTube as a source of information on eye floaters.

It’s the sort of thing where almost anyone who thought about it long enough ought to be able to write the conclusions of the study without doing any of the actual research work.

Which is exactly why it’s so fun that somebody actually DID the research work! Seriously! And concluded, predictably:

• YouTube is not a reliable source of information on floaters…

• …misleading… potentially dangerous…  

• …the best videos are not the most viewed, they’re the ones with the higher like to dislike ratios…

• …sources like AAO are best….

I know floaters are very poorly understood by the general public. But seriously, I think there’s a lot of eye conditions that you could substitute for “floaters” in those conclusions, with everything else remaining perfectly true. Or am I wrong? Is there something about floaters that uniquely brings out the stupid factor on YouTube?

Moving right along… Ah, hello cornea!

Epidemiology, i.e. who gets dry eye?

What predisposes Asian eyes to dry eye?

Jenny Craig of the University of Auckland (also vice chair of TFOS DEWS II) is responsible for this one. If you’re aware of the very high rates of dry eye amongst Asians, did you ever wonder why? (Independent, that is, of environmental and geographical factors.) Well, the part they were able to pin down is differences in the blink: From an early age, there is a higher tendencey amongst Asians to an incomplete blink and to lid wiper epitheliopathy. This research is on its way to the publisher, by the way, so I’ll be putting the full work out there on the blog in due course. Also in the pipeline, I’m told, is possibly some work specifically on the very blinking exercises that may be able to help.

Takushima island

Another collection of data from a population study of prevalence and risk factors for dry eye in Japan, and the first of its kind to include MGD, blepharitis and dry eye in the same study.

Brazilian medical students

29.3% have dry eye, based on OSDI symptom scores, compared to 17.8% in the overall population. Students… take care of your peepers please!

Drops

Not a lot here on drops today (at least on this side… I haven’t had time to hike over to the other side and they’re closing pretty soon, but I think all the dry eye stuff was on this side anyway). But FWIW:

• Alpha lipoic acid eye drops: Poster suggesting they “may” improve tear stability, used 3x daily for 90 days. Notta lotta detail.

• Bascom Palmer paper on autologous serum eye drops providing subjective improvement, with higher likelihood in evaporative dry eye types, verified by phone survey 3 months after starting. Patients in this study 77% male. Serum concentration unfortunately not specified.

Glaucoma

Glaucoma and dry eye in Ghana

There’ve been a lot of really neat dry eye studies coming out of Ghana lately, by the way…

Seems glaucoma prevalence is very high in Ghana in general. But amongst glaucoma patients, they found based on OSDI symptom scores that 81% have dry eye symptoms… and an equally whopping 87% have an abnormal TBUT. 25% of women with glaucoma have severe symptoms as do 22% of men.

…And, how about dealing with the damage from drops?

In another poster, they studied glaucoma patients with no history of dry eye before glaucoma. Those patients were taking an average of 5 drops a day, 3 of which are preserved with BAK. They treated the ones with dry eye with lid hygiene, FML, omega 3s, doxycycline, and lubricants but kept them on the same glaucoma drops.

Dry eye treatments improved redness, corneal staining, vision and OSDI symptom scores. What’s not to like about that?

Conclusion: “Osdi signs and symptoms are prevalent and represent a challenge in glaucoma patients”"

Sigh. Far too many elderly people on glaucoma drops are not being diagnosed or treated for dry eye, still. This needs to change!

Interested in your gut?

Dr Fishman was here with a great poster on an association between dry eye disease and lower gut microbiome diversity! They identified 3 in particular that were lower in dry eye patients. Actually, he had a really smart high school student working on this and she was here to present it. Congrats Abiya Bagai!

Female stuff

Menstrual cycle?

There was a really cool paper called “Influence of somatosensory function and the menstrual cycle on dry eye symptoms”. It’s a little involved, but basically… most research on the cycle’s connection to dry eye (if any) focuses on clinical signs. This one zeroed in on symptoms, and looked at other changes that happen to sensory experience during the cycle that might be related to experiencing dry eye symptoms differently. In the end, they found that there were no significant changes in dry eye signs or symptoms BUT the relationship between signs and symptoms did change during the cycle! Don’t mind me - I get excited about anything that can explain any part of sign/symptom relationships in any circumstances.

Breast cancer treatment and dry eye

Another poster looked at the effects of aromatase inhibitors on signs and symptoms of dry eye.

And… ta da… NOTHING. Or almost nothing. The treatment did not do it. Prior history of chemotherapy didn’t appear to have either.

How often does somebody go around showing research saying that thus-and-such does NOT cause dry eye? (Somebody plausible, that is, as opposed to a peddler of something we all know to be harmful.) I want some more of that. A lot more of that.

Demodex

Poster from Tufts on demodex mite density being associated with reduced corneal subbasal nerve density in patients with dry eye disease (defined as symptomatic plus TBUT under 10).

Headaches

Poster about research looking into whether there’s a dry eye connection difference between migraine headaches and tension headaches (previous research hasn’t distinguished). Answer, not really, although the quality of life impact differed.

Dirty air, indoors or outdoors

Now I’m really running out of time but there were two posters on this (plus a really interesting presentation earlier that I’m hoping to post about later on) - one from Bascom Palmer, saying that indoor air particulate matter content was a significant predictor for dry eye (signs and symptoms). Another from Gachon University in China found that different particulate types differed in their association to dry eye symptoms.

Sleep

Not news, lot published on this lately but for those who missed the memo, it’s absolutely worth repeating: poor sleep quality and short sleep duration are both associated with dry eye symptoms.

Mining Facebook for data on GvHD

This one was fun… they analyzed a facebook group of GvHD users to establish, based on symptoms reported, what percent of GvHD patient members in the group have ocular symptoms. They came out about 25%. The reason it seemed this was potentially useful information is that estimates in published studies are all over the map (19% to 56%) for a variety of reasons.

MGD

Poster from Johnson & Johnson about how common MGD is. Now, of course it really is high, but I’m much less inclined to believe it from the lips of the purveys of Lipiflow. But for what it’s worth… 41.6% in general population, 74% if more than 4 hours on screen time daily, and 76.3% of those diagnosed with dry eye.

Incidentally they also had a paper about dry eye clinical presentation (what’s going on with our eyes), co-morbidities (what else is going on) and healthcare utilization (are you getting help). This was medical claims data mining, and we learned a lot about the pitfalls of that yesterday in the Big Data course. So the idea that only 12.7% of people who were diagnosed with dry eye, had actually been tested for anything, was a stretch to the imagination. To be fair, they readily acknowledged the limitations when asked.

Winding up the day

I have much more to write up - there’s the whole ocular surface session, and also I had a great conversation with the PhD student from Australia who presented on BAK earlier today. But right now, I’m signing off for the day and heading to the TFOS DEWS II dinner.

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.

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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.

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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.

Abstract

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Of mice and mice

Next up:

“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”.

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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.

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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.

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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.

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And one more

Function of lacrimal gland myoepithelial cells in homeostasis, aging and disease

Helen Makarenkova

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.

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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.

Rebecca

ARVO Sunday afternoon - more posters

More poster session notes

Moved over to Section B. There are acres of posters… there really are… and I get to start over tomorrow and Tuesday!

I couldn’t help noticing how many people over here in the retinal research sections had white canes, and a service dog or two even. Definitely a lot of personal interest going on in vision research, and this would definitely be the place to catch up on what’s going on.

Most of that is outside my areas of interest, but I did browse most aisles of posters just to get a sense of some of the trends.

One thing that I saw a little bit more of this time was mentions of patients. You know, US. And what we want and how we feel about things. Considering the push at the NIH & elsewhere to start at least making some effort to involve patients’ voices, though, I was surprised not to see more evidence of this in the poster sessions. At least today’s. We’ll see what the next couple of days bring.

Minor tidbit from the glaucoma section. A poster mentioned, in its background information, that long-term benzalkonium chloride exposure is a risk factor for dysfunctioning blebs. Just what I needed, another reason to dislike BAK.

Then came cataract surgery: I browsed this section for anything dry eye related. Usually when I think of cataract and dry eye, I think of dry eye after cataract surgery, but this time I was noticing things like increased efforts to detect and treat dry eye before cataract surgery, not but because of dry eye concerns per se but because of how undiagnosed dryness could interfere with calculating the intraocular lens power. There was a poster from Melbourne on using the axis of astigmatism to identify subclinical dry eye, and another on tear osmolarity because of how a poor tear film can affect keratometry readings.

And more cataract: A poster from Central South University in China studied MGD patients before and after cataract surgery and determined that while they may have worse symptoms after cataract surgery, the MGD itself doesn’t get worse following surgery.

Then I meandered back to the other section where most of the cornea stuff was, in case I missed anything, and sure enough!

New! HL-036 (HanAll BioPharma): Phew, I didn’t even have this one on the radar, but I looked it up and I see that they recently started recruiting for a Phase 3 clinical trial! Just added it to the pipeline page. In the poster presented today, they compared two different concentrations with placebo. The lower one had results similar to placebo (in terms of clinical signs) while the higher was much better.

Then there were two posters on slow release cyclosporine. One had too much of a crowd for too long and I lost patience. The other one, I allowed the author to talk me through the entire store. Very nice young man and he’ll never know quite how much of it was over my head. It was actually really interesting, but the particular work he was doing was nowhere near human studies.

Missing in action: There was a poster I was really looking forward to and it had been highlighted as a “hot topic” in the press office… It was about an OCT imaging process to quantify inflammation. I was so disappointed to find that the presenter had withdrawn from the meeting at the last minute. But I looked up the paper in our app, and here’s the gist of the conclusion: “Magnetic nanoparticles can be visualized using OCT… The high sensitivity suggestions that the visualization of inflammatory cells labeled by functionalized nanoparticles is possible…” It’s in very early stages but sounds promising. From a patient’s standpoint, “inflammation” too often sounds rather nebulous and subjective. The idea of imaging for it sounds fascinating.

I always forget…

…how hard convention centers are on the eyes. Exhibit halls especially, but maybe I just noticed it more there because I spent so much time there in the poster sessions. Cool, dry, blowing air everywhere. I love coming to these things, but by halfway through the day, my lenses get so uncomfortable and my eyes are so light sensitive I want to screen.

Anyway, I made it a relatively short day today - left when my laptop battery and my eyes had both given out. Tomorrow will be quite full - back to back presentations most of the day plus a dinner tomorrow night.

ARVO Sunday midday... posters and more

No pix

Sadly, we’re not allowed to take pictures anywhere at all at ARVO.

Like they drill it into you so aggressively that I’m wondering if they mind me photographing the sky above the building.

I mean, I understand it in the poster sessions, but in presentations too? Sheesh. Ah well. Getting more efficient about taking notes in Google docs on my phone.

Posters, posters and more posters!

Wavefront guided scleral lenses: This is in my personal future so I was interested. University of Houston College of Optometry. Talks about how sclerals tend to decenter inferotemporally and they have to adjust for this case-by-case. They want to reduce design complexity so the study was aimed at simulating optical and visual performance degradation. (Note to self - does lens size play a role?)

Antibiotic resistance: Update from ARMOR study - comparable to 2017 results.

Neuro stuff, dendritic cells… lost count of all the posters on this.

Tacrolimus: Talked about the use of this in ocular surface disease. 0.1% tacrolimus ointment in a number of severe disease applications including limbal stem cell deficiency. Effective for inflammation but caused surface irritation.

Depression alert… SSRIs and dry eye! Study from Fudan University… very interesting. They looked at 20 and also rats. Need to get hold of the authors and come back to this one.

Rusiteganib: Just saw something in the news about this the other day but nothing in that press release about actual results. Hoping to circle back.

Anxiety alert: Keio University. Effects of topical dry eye treatment on anxiety related behavior in mouse dry eye model. “We have advocated a vicious cycle of environmental stress, dry eye and depression as a hypothesis”. Concl: “current study revealed that topical dry eye treatment may improve anxiety related behavior”. In this study, they used rebamipide (WHICH WE DONT HAVE in the US which is really annoying!)

VivaVision biopharma, Shanghai, VVN001 “Potentially better efficacy and safety profile than lifitegrast”. Mmm sure.

Trehalose: Two posters on this, slightly different conclusions… both looking at the combo trehalose + HLA (Thealoz Duo). 2nd one indicated symptomatic relief but not protective effect in adverse environment. 1st one indicated osmoprotective benefits.

Drop turns to gel? Wakamotob pharmaceutical, AT-1401 thermoresponsive artificial tear. Designed to last longer by gelling on the eye surface. Hm.

Systane Complete: Showing it supposedly better than Refresh Optive and B&L Soothe. You know what? Ditch the friggin’ preservative, please.

Dry spots interfering with pressure measurements? Paper showing both under and overestimated intraocular pressure with certain instruments depending on whether SPK was present.

PROSE “Plus”? Mass Eye & Ear - use of bevacizumab in PROSE devices to treat neovascularization… exciting!

Then I got lost in a sea of Keratoconus posters.

Then I moved on to the exhibits.

Preservative-free multi-dose: Connected with a vendor, Nemera, who make preservative-free multi-dose packaging for drops and who were interested in what I had to say about the need for both OTC and Rx drugs in preservative-free options in the US… The conversations made it even clearer to me what a steeply uphill process it will be to get PF drops on the US market, but raising awareness of this need is a key priority for the Dry Eye Foundation.

Speaking of which: I also connected with an international network of glaucoma associations. They have just recently decided to possibly start allowing patient organizations to join their network. Think of being able to team up with glaucoma organizations on raising awareness of the need for preservative-free glaucoma medications!

I’m down to 12%. How is it I thought my battery would last out the day? Hm.

ARVO 2019 - Sunday morning and big data

It’s a beautiful morning here in Vancouver!

First order of business

Find the press room, get my badge and get online! Somehow couldn’t get my ARVO account activated correctly on current email address but that’s all fixed and their handy-dandy app will tell me me exactly how many minutes to get from where I am now to wherever the heck that course is…

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Big Data

Delectable, simply delectable. I have dreams of what big data could do in the dry eye world. It’s far too immature as a science for the data to be all that useful for research per se (for example we are nowhere near having core outcomes established) but it doesn’t have to be completely ready for the big-time for it to be useful. Trends identified in big data could point the way to suspicious gaps, could validate known problems, could help patients contextualize their experiences, could help patients formulate questions to ask in order to more effectively advocate for themselves, long before the data and the big data analysis methodologies are ready for it to become a useful adjunct to clinical trials.

I can’t geek out too much about the presentations this morning because I’ll get hopelessly behind - past experiences have taught me that if I want to sleep between now and Wednesday, I have to both blog during the day and keep it snappy. Not that I know enough to truly geek out anyway, but I do like pondering stuff.

Incidentally, I know perfectly well I’m writing a blog post no one will read, but writing helps me sort out and summarize my own thoughts about what I heard, and that’s good enough for me today.

Laura Balzer (UMass) gave the opening presentation. A lot of it could best be described as approaching a room full of highly sophisticated balloons with two fistfuls of even more sophisticated pins. Kablooey. You think you’re a scientist? Watch her find and expose all the wrong assumptions you may be making about the soundness of your approach to big data. Among the many take-home messages: Big data does not solve any of the usual fundamental research problems (eg correlation vs causation), and actually causes new problems. For example, you might be really surprised at what’s actually lurking in what seem to be fairly trivial missing data, so don’t get ahead of yourselves.

Michael Chiang (Casey Eye OHSU) brought the discussion into ophthalmology. He highlighted the problem of the very, very long lag time between when science discovers things and when the new knowledge actually changes patient care. (It’s 17 years.) Then showed us how they tried to use ‘big data’ to improve patient wait times in their clinic. It was really kind of fun to hear about - not just the technical parts but the extent to which data analysis contradicted opinions. For example, some patients take a long time right? (And did you know that they know who you are, by the way?) So do you schedule them at the beginning of the day (which is what they used to do but then they discovered through big data how badly that threw everything off for the whole day) or at the end of the (in which case you piss off the entire stuff because nobody goes home on time)? Big data helped them optimize between not messing up the schedule and not having a ridiculously long day.

After data analysis, he went into the question of data registries like IRIS (covered later) and more twists on the notion that observation changes things… in this case, that measuring things improves quality, as they’re finding in electronic medical records (paper is in press now about this).

Joshua Stein (UMich) then got into the real meat of the matter as regards big databases and some of the issues going on. He started with the medical claims databases. I loved this because we’ve been seeing more studies published lately in dry eye that were based on claims and I wonder sometimes about the implications and limitations. He outlined the key issues and challenges with this type of data, such as a how “messy” it is (80% of medical data is unstructured, for example, text descriptions that you can’t always accurately extract data from automatically. He talked about the areas of research that this type of data is useful for, and what it’s not useful for. One of the problems is that everything’s based on insurance codes and there are a lot of issues with the quality of the data.

Next source he mentioned is the American Academy of Ophthalmology’s IRIS database (covered by Dr Coleman below), and last, his SOURCE database project, which currently has about 300,000 patients. It’s a collaborative thing that taps into EPIC, software removes patient data, pools it with diagnostics, test data, genomic data, etc, then makes it available to participating institution researchers. His bottom lines were that the data, to be more useful, needs to move beyond insurance codes to being disease-based, and needs to be more granular. He sees the role of big data as preparing the way for clinical trials - learning as much as possible before the huge investments in those trials. Audience member pointed out that it could also be hugely helpful for clinical trial recruiting.

Christopher Hammond from St Thomas’, London went into the big data genomics in biological research. Super interesting, just not to me right now. I was mildly amused when an audience member attempted to raise the specter of patient privacy. Her hypothetical: “If an employer knew that based on your genomics you are likely to have X eye disease within 10 years, they won’t hire you. How do we prevent this?” did not elicit a more nuanced response than “Well, they agreed to let their data base used.” Ah well.

Anne Coleman (Jules Stein/UCLA, also president-elect of AAO) then presented on the IRIS registry, which is a database system created in March 2014. They have data on 53 million patients now and it’s integrated with 55 different electronic health records systems. The goal of IRIS was described to be closing the loop in the process of establishing care standards, so as to substantially shrink that 17-year gap we talked about as taking place between discovery and new care standards actually being adopted. As she was presenting data on glaucoma, I couldn’t help but think (warning: soapbox) about how long we have had data on the harmful effects of benzalkonium chloride in glaucoma medications and yet clinical practice is moving at a glacial pace towards broader use of either preservative free formulations or less toxic preservatives in glaucoma medications. Sigh. Anyway. One of the many points she made was that big data can help in research by finding small, statistically significant differences that can only be found in very very large data samples.

Dr Coleman talked about all the different research opportunities using IRIS, including (1) IRIS registry analytics teams (5 teams in process or completed?) (2) Joint project between Research to Prevent Blindness and IRIS (3) Hoskins Center IRIS registry research fund (4) American Glaucoma Society IRIS Registry research initiative and (5) Knights Templar Eye Foundation Pediatric Ophth IRIS reg research fund

In terms of impact, there have been several studies published already with IRIS data, and it also has the potential to influence policy - she mentioned an example of the FDA wanting to restrict use of drug bevacizumab (because of compounding errors) but they were able to demonstrate with IRIS numbers how small the actual impact was so the FDA didn’t. (Incidentally I noticed later on in the poster session that there was a poster about using this drug successfully in PROSE devices to treat neovascularization.)

An audience member posed the question of whether she could envision a world where patients have some kind of access to this data, for example, to see data on their provider in a greater profession-wide context, and the answer was a simple no. Another asked whether there could be synergies between what AOA (i.e. optometry) collects versus AAO’s IRIS. Answer: It’s something we’re interested in.

Dr Chiang wrapped up the session by saying that bringing together different people from different fields is what advances the field, and that that is his vision for the role of big data.

Moving on!

Blog post #1 at ARVO… somehow this does not appear to qualify as “keeping it snappy”. Next!