Conferences

ASCRS, day three

Another information-rich day…

…though slightly more frantic. With two medical sessions and a lot of individual meetings lined up (as well as a flight to catch before dinnertime) this was a day of running from one place to another.

MGD session

Diagnostics

  • Dr Bose presented on infrared meibography in MGD and dry eye syndrome. The point of the study was to relate the tear film to meibography results using a grading scale of 0-3 (0, no loss; 1, 1-33% loss; 2, 34-66% loss; 3, 67%+ loss). A higher grade of dropout correlated with poor tear break up time. (We do not, however, know how that correlates with symptoms.)

  • Dr Farhat presented on meibomian gland changes with age as shown in meibography. Their purpose was about how we can diagnose people earlier in order to have better outcomes. They studied 272 patients aged 20-89. There was a very interesting bar chart, more up and down in there than I would have expected. They did not find meibography to be a good screening tool for MGD.

  • Dr Greiner presented on punctocanthal epitheliopathy in MGD. They studied patients with and without symptoms (based on the SPEED questionnaire). PCE staining was much greater than LWE staining in both groups. Bottom line: “PCE is an easily observed marker for MGD” i.e. a simple way to figure out if you have it.

Lipiflow

  • Dr Hurai (UCinci, J&J sponsored study) presented data challenging the notion that atrophied meibomian glands don’t come back. 68% showed visible improvement in gland structures after Lipiflow, and opened the question of what gland loss means - I didn’t quite catch the wording but to the effect that we need to be questioning whether what’s being seen is evidence of a loss of functioning structure or simply a loss of activity (but resurrect-able structure).

  • Dr Tauber presented data that seemed to show Xiidra basically matched Lipiflow’s results in terms of improvement to both clinical signs and symptoms in both inflammatory and obstructive MGD. “Just a pilot study” as he pointed out.

  • Dr Reddy presented 3 year results of Lipiflow (no industry funding). I really enjoyed the way they looked at this, a great reminder of the heterogeneity of MGD and dry eye and the whole sign-symptom thing. They broke patients into four groups - those who had improvement to both signs and symptoms; signs but not symptoms; symptoms but not signs; and neither. A lot of it went by way too fast for me to get the details I wanted, so I’m hoping to circle back to him for more info. I also had a note that he indicated they saw better PRK surgical outcomes when patients had Lipiflow.

  • No-show for another lipiflow presentation, hopefully it was the least interesting one!

  • Dr Matossian presented on the effect of Lipiflow on keratometry prior to cataract surgery. In half of patients, they went from against the rule astigmatism to with the rule astigmatism, the other half the reverse and just one patient (out of 23) unchanged. 16 patients had an increase in the amount of astigmatism. She stated that 40% of the time, her treatment plan would change. These things… sure would matter in a vision surgery.

Miboflo

  • Dr Gomez compared results of 1 lipiflow treatment to 3 miboflo treatments (done 2 weeks apart). The results for both groups were similar; the mibo patients were somewhat happier; but she also showed how the effects of the treatment wore off over time till patient was back to baseline by a year from treatment. However, they also felt that the Miboflo patients may have been doing more at-home maintenance treatment.

  • Dr Gauro presented study data on Miboflo - 46 patients, average age 54, 91% female. They studied OSDI, TBUT, staining and complications. Patients had 3 sessions - at days 0, 15 and 30, for 8-12 minutes, and final evaluatoin on day 90. All numbers improved and there were no side effects. Staining was only mildly improved. They recommend Miboflo for grades 1-2 on meibography but not for grade 3.

IPL

  • Dr Gauro studied the therapeutic effect of IPL alone (without expression). This is an interesting one because a lot of people dismiss IPL as not meaningful claiming that the patients benefit simply from the expression that always accompanies it. So they studied 36 patients (but lost 10 - yikes!). with sessions on E-Eye on days 0, 15 and 45. OSDI was reduced by 83% at 46 days, 60% at 136 days. TBUT, more. Staining, significantly reduced. I found it amusing that during questioning, they were asked why they would study this without the expression, when it’s known that the expression helps.

  • Dr Quesada presented results from 70 patients in El Salvador with evaporative dry eye. They had three treatments (day 0, 14, 30) and were evaluated for 6 months. Patients were average 58yo, 72% female and with moderate to severe dry OSDI scores. Their TBUT went from 4.2 to 14.6 (but that went down after the 6 month point). Tear meniscus doubled, then dropped a bit before the 7 month point. Meibography improved though I didn’t catch the numbers.

Pipeline drugs

  • Dr Tauber presented on a pipeline drug (NOV03) that they feel goes into the glands and unblocks them.

Demodex

Dr Rosenberg presented on prevalence and demographics of demodex. Among the findings, 83% had demodex after pterygium surgery, and only one out of 82 patients who had blepharitis secondary to demodex was being treated adequately. Patients using OTC drops had a lower incidence.

Conversations

I got to meet Vanessa for the first time, though we’ve known each other for a great many years. Vanessa is a journalist who covers a wide range of ophthalmology topics, and we have often connected over the years when she’s reporting on dry eye. So fun to finally have a face to the name!

Then I had the privilege of lunch with David, a Facebook friend experiencing dry eye pain… he picked me up and took me to a fabulous ‘hidden gem’ type Mexican restaurant (the line winding down the road is excellent proof of their popularity!) where I ate far too much and got to here his story and all about the extraordinary paths he has been down in the search for solutions. I never cease to be amazed at the resourcefulness and effort that people manage to put into the search for answers and solutions, and also to be heartened by the extent to which they often turn around and, like David, help others in their journeys.

Exhibit hall

Johnson & Johnson

They had lots of space dedicated to Lipiflow, but nobody there who could talk about over-the-counter products (Blink brand, and Visine brand for that matter since many of those BAK-laced drops have dry eye in their listed indications). Had some good conversations about the role of symptom surveys in assessing how well Lipiflow’s working for patients over time.

Random observation

Sometimes we have no idea, no idea at all of the challenges that come up in manufacturing and prevent products from coming to market the way we want. I think that the opacity of this process certainly works against perceptions more acutely with the larger pharmaceuticals, because their public face (the public information phone lines) is so impersonal, disconnected and corporate.

Oasis

Oasis are the leader in sodium hyaluronate drops… they’ve been going strong for a long time. Looking forward to the preservative-free multi-dose version of Oasis Tears Plus which is due out later this year reportedly. They have having a bit of a shake-up in their lid scrub selections, and are developing some new things which are expected to come out later this year.

There are so many more I met with, but…

Too much stuff, too little time! Moving on to the medical stuff.

Dry eye session

Biological products

SERUM: Dr Yamada presented results of a study on autologous serum where emphasis was placed on patient satisfaction, ascertained through a series of questionnaires. Patients used 30% serum 4-6 times daily for anywhere from one month to three years. SANDE scores dropped from 79.5 to 42.2, i.e. roughly in half, and all other topical medications (both prescription and over the counter) were reduced while they were on serum.

PRP: Dr Melissa Toyos presented on the “Genius PRP System” that they use at the Toyos clinic. She talked about the lack of standardization in protocols for preparing serum drops, and about how we have ‘barely scratched the surface” and how PRP has up to 8x the growth factors as serum. She presented data on 20 patients, however, more than half of them were also getting IPL, so I don’t know how you would decide what’s helping.

AMNIOTIC MEMBRANE in GvHD: Dr Ham Yin presented a case report of a Graft-v-Host Disease patient in a flare-up where they used sutureless amniotic membrane. What was impressive is that the patient ended up having no symptoms at all for two months, and at that point went back on cyclosporine and artificial tears. He also said that in a recent study in mice, they were able to prevent ocular GvHD from developing in the first place.

Cyclosporine

Dr Sheppard presented on CyclASol, a phase 2b/3 study, where the primary endpoints were corneal staining and OSDI symptom score. Both improved, and they also reported that reading speed improved, which was interesting, and tolerance was good (2% or less reporting discomfort on installation). A confirmatory clinical trial is expected to start this year.

Dr Matossian presented on Imprimis’ Klarity-C, a study meant to evaluate efficacy and tolerability of this drug which is a higher dose than Restasis, which as we know has a lot of tolerance issues. Endpoints, again, were staining and OSDI. The trial was for 90 days. Staining and OSDI results were strong, and interestingly, about 1/3 of them actually dropped into a “normal” (i.e. no dry eye) range on OSDI which was impressive.

Pipeline drugs

OC-02: Dr Holland presented results on a Phase 2b trial of Oyster Point’s nasal spray for dry eye (165 patients). I didn’t catch the sign/symptom result details (though symptoms were a visual analog score). Side effects / complaints from the spray were comparable to other nasal sprays. Phase 3 trial should begin this year.

ALG-1007: Dr Donnenfeld presented results from the first human trials of Allegro’s drug, a peptide integrin inhibitor in a hyaluronic acid base. The results for the highest concentration studied showed up quickly and were strong, and it was well tolerated. However, considering the HA vehicle, one of the moderators questioned how they will control for that in the future to make sure the results aren’t attributable to the HA. A second phase 2 trial will be presented this fall at the AAO meeting.

Botox for photophobia?

Dr. Venkateswaran presented data from Anat Galor’s group at Bascom Palmer where they looked at whether Botox would help photophobia and dry eye without migraines (it’s been studied in migraines specifically). it was only six patients and very short but… their light sensitivity improved (although their dry eye clinical signs did not). She talked about trigeminal nerve sensitization.

Lipiflow as a surgical prep?

Dr Vaishnav talked about “20/unhappy” refractive surgery patients. These were very symptomatic patients with high OSDI symptom scores, and they found in confocal microscope examinations that they had “nerve loops”. Those who had high OSDI scores also had a higher percentage of dendritic cells. They did a study where they did lipiflow on evaporative dry eye patients before refractive surgery and measured lots of things about their tears before and after, and felt that Lipiflow “reduced inflammatory and nociceptive factors on the ocular surface, thus reducing the incidence of dry eye and nonciceptive pain post surgery”. Sigh. Can’t we just not do refractive surgery on high risk patients?

Buffering the burning eye drops

Dr Epitropoulos discussed the common problem of patients complaining of discomfort from Restasis and Xiidra. She presented results from a study where they used Rohto “cooling” drops before or after Restasis or Xiidra to see if it improved comfort. I’d love to have seen this compared to any other artificial tear incidentally (what’s special about Rohto?). There were 33 patients and they only included patients who were reporting an irritation from their prescription drop of 4 or higher on a scale of 1-10. She had them use Rohto either 5 minutes before or 5 minutes after the prescription drop. 96% percent experienced improvement. In discussion afterwards, someone questioned why 5 minutes and whether that would affect drug retention time on the eye surface. (Incidentally, even the AAO cites 5 minutes as a safe rule of thumb, but where’s the science?)

Neuropathic pain treatments

Last, three residents in a row reported on pain treatment studies from Bascom Palmer:

  • Gabapentinoids (7 patients): 2 resolved; 3 significant improvement; 1 slight but noticeable improvement; 1 no improvement. Higher doses were more effective.

  • TENS (8 patients): 6 patients used it consistently up to 3x daily for 3 months, then decreased to 3x a week. Pain dropped about in half from 8/10 to 4+/10 (dryness and light sensitivity did not improve, but pain did). 2 patients did not benefit and stopped using.

  • Nerve block: Case report of a successful treatment.

That’s all for now….

There is so much more that happened, so many more conversations and things learned… sadly, there will never be time to write about it all! Anyway, one last great huge THANK YOU to everyone who helped me to this by contributing to my GoFundMe travel fund. I appreciate you!

ASCRS, day two

Exhibit hall

Trends

  • Hypochlorous acid: It’s everywhere. As I’ve been saying, it’s well on its way to becoming the new Omega 3, in terms of ubiquity.

  • Sodium hyaluronate: It’s coming to more drops in the US, which is a good thing.

  • A “complete solution”: Most companies in the dry eye space that are doing anything at all in over-the-counter and/or consumer products is broadening their reach to cover eyelid care plus eye drops. Dry eye treatment used to be “plug & drop”. Now dry eye care is “Drop… plus clean, heat and squeeze, and wash down some Omega Threes while you’re at it”.

  • Plugs: 6 month dissolveables are all the rage, and everybody’s got their own partial occlusion (“flow controller”) style plug now too.

Ocular Therapeutix: Dextenza

This is not a dry eye drug, it’s a slow release tapered dose corticosteroid. It’s designed for post-surgical use. But the reason I’ve been interested in it is the potential to provide a BAK-free steroid treatment alternative for those patients who are allergic to the BAK preservative which is in almost all steroid eye drops, without them having to resort to costly compounded PF steroid drops that their insurance won’t cover.

Random observations about dry eye in the exhibit hall

  • A woman I met with at one company could have been Exhibit A for the Vampire on your Vanity talk.

  • A young man at another company that I happened to stop and chat with told me his eyes feel dry pretty regularly and asked what he should do. How to answer that? My first instinct, of course, was to suggest he see an eye doctor (oh the irony), but lest he end up in the hands of one who gives out cookie cutter treatments without any differential diagnosis, I went ahead and gave him the schpeel about how the most common form of dry eye is the oil glands, and suggested some simple questions to ask them….

  • Several people I spoke with are in my age range (I’m 50) and have an elderly parent with glaucoma or other ongoing eye problems. They were very aware of the level of discomfort it’s causing, but don’t necessarily know anything about some of the contributing factors, such as the glaucoma medications, or the treatment options. And this… is at an eyecare conference.

Kala Pharmaceutical

Some data were presented about Kala’s drug KPI-121 yesterday in the dry eye session. This is a low-dose steroid meant to be used for two weeks for a dry eye episode. (And yes, it is BAK preserved, but also only intended to be used for short courses, so at least it’s relatively short exposure, but important to know if you’re allergic.) In a lot of their presentations and literature, the place they are carving out for these drugs is based on the understanding that dry eye patients have “flares”. They' have another clinical trial ongoing, just measuring symptoms, and it sure sounds like there is strong reason to believe they can have this approved and on the market in 2020.

Escape

Something went wrong with a lens at some point, and I really didn’t want to deal with it there, so I had to head back to the hotel to deal with it and let my eye recover a bit that afternoon….

NuLids

I talked to their folks on the phone quite a bit and I have one of the NuLids devices at home… not that I remember to use it very often. I am very much a fan of the concept though, of a device for home use that is dedicated to keeping the lid margins squeaky clean. It’s pretty easy to use, reasonably comfortable, and not that expensive. People complain about the cost of the replacement tips, but honestly, it’s still an awful lot less than a lot of things people are spending money on for dry eye these days.

Vital Tears

Another drive-by to say hello. No particular news, but if you’re not familiar with Vital Tears, their raison d’etre is making it easy for people to get autologous serum tears. And they definitely deliver on that promise. Check ‘em out.

Random thought

I often think, these days, about the anxiety driving so many dry eye or eye pain patients to churn through everything from information to doctors to treatments, sometimes many at once, always in rapid succession. What will it take, what would it take to help someone in that state to slow down and start being methodical enough to actually help themselves?

LacriVera

The plug wars! It seems like plugs went from vogue to not quite so much to now coming back more, at least based on how the supply chain is proliferating. Anyway, the LacriVera family looks like this:

  • “Permanent” types

    • VeraPlug (baseline version)

    • VeraPlug Flow - their partial occlusion version (reduces but does not eliminate tear flow)

    • FlexFit (complete with 45 day retention pledge)

  • Dissolvable types

    • VeraC7 (collagen 7 to 10 day plug)

    • Vera90 (synthetic 60 to 180 day plug)

    • Vera180 (synthetic absorbable 6 month plug)

Bruder

Bruder were the first to popularize a bead-based microwavable warm compress and they’ve done a good job with it. There are now, of course, a ton of lookalikes on the market, so it’s harder for them to differentiate themselves, although their lovely marketing materials sure try hard to, touting their silver-infused “patented MediBeads” versus silica gel beads or other materials, and better durability and washability. All of that seems like reasonable claims to me, but the “two-pod” design that they sport is something I think could cut either way, with some preferring the one continuous compress.

Bruder have several items now specifically for dry eye:

  • Moist Heat Eye Compress (the classic thing)

  • Hygienic Eyelid Sheets (handy liners, sold in a box of 35 individually wrapped)

  • Cold Therapy Eye Compress (gel pad, gets colder than the other thing)

  • EyeLove Contact Lens Compress (am I the only one that finds this confusing? Is it meant/allowed to be used when you’re wearing contacts?

  • Hygienic Eyelid Solution (hypochlorous acid 0.02%, and they seem to be claiming is the only one that is pure like Avenova, but higher concentration… I’m looking into this)

Lacrimedics

Rats, I thought I got some materials, but I can’t find them now. Anyway, they have new plugs coming out, one classic, one flow controller style.

Random idea percolating

Yesterday, I was talking with the head of an intraocular lens company that had created their own software to reach out and check in on the progress of patients by email for a couple of years after their eye surgery. I really liked the concept of how it worked - and simply the act of reaching back, routinely, to all of them. With my dry eye hat on of course I’m thinking of ways they could flag and reach out to people who are unhappy with their dry eye status afterwards and might otherwise just move on to another provider if they don’t feel they’re getting enough help.

From there, the creative juices got going and… I started pondering, and started noticing all the companies in the exhibit hall whose business centers around managing communications (email, text, etc) between eye care practices and their patients. What if… those constant contact systems incorporated an OSDI dry eye survey, which would serve both to let the patient know the severity level of their dry eye AND alert the physician’s office to patients who really need some dry eye follow-up even if their surgery was otherwise successful? Hm, hm, hm.

So I started poking around and talking to additional companies. I got a lukewarm response from most of them (as I expected) except one. Thanks to a smart staffer who matched us up, I ended up talking to a head of another company who turned out to be at least as much of a data-lover and database-visionary as I am… the difference being, he actually has the technology and has access to something like 24 million patients via several systems united under the same roof, where ideas can actually come to fruition. It was so much fun learning more and drooling and fantasizing over all the software projects that I believe could help people with dry eye. The time will come!

EyeVance

EyeVance recently acquired FreshKote from Focus Laboratories at the same time (if I understand correctly) that it went from conventional to preservative-free multi-dose packaging. FreshKote continues to be a bit of an ‘orphan’ product - which is sad, from my standpoint, as I remember when it was one of four wonderful products, and I just wish the others could some day return to market.

ASCRS, day one

Arrived! (the night before…)

What a great time of the year to be in San Diego! Lovely and mild. I drove down from Claremont Friday night, after attending Aidan’s glee concert at Pomona on Thursday and spending all day Friday in a joint intensive Dry Eye Foundation work session.

I’m staying at a fun little place not far from the convention center, the Horton Grand hotel. All I knew at the time that I booked was that it was the cheapest one on the convention’s list that still had rooms available, but it reminds me a lot of the hotels in Port Townsend out on the Peninsula west of home… old restored buildings.

The very best thing about this hotel though - and some of my old LASIK buddies will surely relate - is the lighting. One of my vision issues is extremely poor contrast sensitivity, as a result of which dim lighting is torture. I dread arriving at hotels late at night when my eyes are at their worst only to have to fumble all over the room to find switches, and even then, with every one of them on, to have a poorly lit room. At the Horton Grand, the moment I walked in the door, I found two light switches which turned on two nice bright overhead lights. HEAVEN. How many hotel rooms have overhead lighting?

In this blog post:

1. Exhibit hall day 1

First day, notes from seven companies related to dry eye

2. Scientific session on beauty and dry eye

All about eyelash enhancements, cosmetics, and other beauty products and procedures and how they affect dry eye.

3. Scientific session on dry eye (scroll way, way down)

Diagnostics, treatments, pipeline drugs and more… lots of study results presented and discussed.

Exhibit hall (May 4)

Random observations

It’s not as big as, say, Vision Expo West, but it’s… pretty large. More than that, though, it’s opulent. That’s my main memory of ASCRS meetings past. It’s all about refractive surgeries, from LASIK to fancy upsells on your cataract surgery lens implants. There is a lot of money kicking around. It makes for some beautiful booths, a decent amount of free food and drink, and nice thick carpeting.

Scope ophthalmics

A lot of the European and Canadian members of our online groups are familiar with Scope as the source of Hylo eye drops, especially Hylo Forte. These are great examples of typical HA drops available almost everywhere in the world except, for the most part, in the US. Hylo drops are deservedly popular and plenty of people buy them in the US from shady Amazon sellers (yes, this is possible, and it is one of the few examples of how Amazon’s UTTER disregard for the FDA may work in consumers’ favor). I stopped by because I wanted to see if Scope have anything new going on and also to get a read on whether there’s any likelihood of trying to expand into the US market.

… We interrupt this broadcast to explain some minutiae about “HA”…

HA = hyaluronic acid. If that sounds scary (acid?), it’s actually not. In fact, it will probably show up on a product label as sodium hyaluronate, which is a much more user-friendly term. Anyhoo. HA is very good for the cornea. Well-made drops with HA (not all are…) tend to be very popular and even the lesser ones are pretty well liked. The problem? HA is not allowed in over-the-counter eye drops in the USA, thanks to the FDA’s antiquated 1970s standards. Except that the Polichinelle’s secret of those selfsame restrictive standards is that you can actually put pretty much anything you want in an eye drop in the US as long as you list it in the “inactive ingredients” list rather than the “active ingredients” list. We used to do this with the Vitamin B12 in NutraTear and Vitamin A in Dakrina, away back in the day before Freshkote. Allergan does this with the oils in Optive Advanced and Mega 3 and now HA in Refresh Repair. Oasis does it with HA in their drops. TheraTears does it with the trehalose in their newest drop (more on that shortly). So you can do anything you want, really, but the hitch is that if you list your beloved ingredient in the inactives, you can’t make “medical claims” for it. That is, you can’t go around advertising it and telling everyone how great and effective this ingredient is, out of one side of your mouth, when out of the other you’re stating on the label that it’s an inactive ingredient.

Ah me, the complexities of working around a thoroughly uncooperative FDA. Cue the violins.

…And now we return to Scope.

No Hylo line to be seen at ASCRS - instead they are touting their new Optase brand. This new brand follows the now thoroughly predictable “family” of products that is de rigueur for any small eye drop manufacturer: make it a family - take care of the lids. So they are sporting a conventional microwavable compress plus a conventional tea tree lid wipe with HA. But they also have some interesting lubricants including a preservative-free dry eye spray which is expected to come to the US market some time later this year, and a new HA preservative-free drop in development. It’s funny, sprays never really took off in the US but I think they’re a pretty interesting way to deliver some moisture.

Rayner (Drops in Europe)

Rayner is a UK-based intraocular lens manufacturer but they caught my eye because they have some brand new HA preservative-free drops (Aeon brand). They are marketing them specifically for post-surgical use, but I understand they are also available on the UK Amazon site. If you’re in the UK, look ‘em up.

Allergan (Drops and ointment)

Refresh PM, everyone’s heartthrob ointment (for those who actually like ointments) is still on the same timeline as I was told last November, which is reassuring - they fully expect it to be in stores on schedule later this year.

Refresh Repair (Allergan’s newest dry eye drop) is coming out in a version labeled for contacts, which is great! Better, though, is that it’s coming out in a preservative free multi-dose eye drop which is expected in stores this summer. Will they ever cross the two and make the contact lens version preservative-free? Possibly. There are no PF contact lens drops on the US market and I imagine if anyone crosses that line, it will be Allergan.

Preservative-free multi-dose packaging, by the way, is definitely the trend to watch in eye drops. This is a good thing, because we want preservative-free, and bottles are more economical than vials. The downside is that the bottles are more difficult to learn to use… there is definitely a learning curve.

Once we actually have some of Allergan’s new bottle, I’ll be doing a YouTube video with all the preservative-free bottles on the market and how they work.

Random observation

There are an awful lot more suits at ASCRS than there were at ARVO. Just a part of the completely different atmosphere.

Digital Heat Corp (Heat treatment)

This is one of the companies I’ve been interested in because of their “warm compress” device. They have a version for use in-office and a version for home use. They’re expensive, but interesting. It’s a wearable powered device, and limits the heat to just the areas that need them. I’m going to get a sample to try out.

Akorn (TheraTears, drops and lid stuff)

The TheraTears product line has one recent and one brand new addition:

  • Theratears EXTRA, with trehalose, a new eye drop. I’m still waiting for them to get back to me on the trehalose concentration.

  • TheraTears Sterilid Antimicrobial, a hypochlorous acid (0.01%) spray for lids… yes, they’ve jumped on the same bandwagon as everyone else. But I love that they have the concentration of every ingredient on the their list… who does that?

Avenova

Avenova is the classic name brand prescription hypochlorous acid lid cleansing product. It’s an interesting-looking world now that there are so many over-the-counter hypochlorous acid alternatives (I came across, let’s see, I think at least three more new copycats here at ASCRS).

Sun Ophthalmics

Sun is the maker of CEQUA, the new cyclosporine eye drop, and the big question is when is it coming and how much will it cost! Timing looks like July, and it sounds as though they are sensitive to the high cost issues of Restasis and fully intending to make CEQUA more accessible.

Bausch & Lomb

Despite an awful lot of floor space, sponsored areas etc, they had no staff at ASCRS for any over-the-counter products, which surprised me. But from what I could find out it doesn’t sound like they have anything new in the works for their OTC product line, either. I asked about potential for a preservative-free Lumify and that is not sounding likely. None of this is surprising from the company that still puts BAK in two of their artificial tears! Bausch, we’d like to see you start paying attention to the needs of the dry eye world.

Sessions (May 4)

Vampire on the Vanity

This was the killer session! I wish everyone could have been there! Now I am stuck trying to interpret my very messy hand-written notes from a week and a half ago. Hate it when I do that. If any of the presenters happen across this I hope they’ll forgive-and-correct any particularly egregious misquotes.

1. Eyelash enhancements, tattooing, and more.

Dr Matossian started us off with an exhaustive talk on quite possibly every potentially harmful eye-enhancing beauty procedure that’s ever been proudly sported anywhere from a nightclub to the Met Gala, from all forms of eyelash extensions to some quite shocking examples of jewelry implants.

Some of my general take-homes:

  • People get trapped into progressively more harmful eyelash-enhancing products and procedures. They become intolerant of one and move on to the next, in a harmful, addictive vicious cycle.

  • Where you get a procedure done really matters. If you’re going to do it at all, go to someone who does it in an eye doctor’s office and has proper certifications. Beauty parlors… not so much.

  • The length and curvature of our eyelashes is actually determined by nature for optimal protection of our eyes. Longer lashes make ocular surface disease worse! Changing your lashes can actually create a “wind tunnel” that directs particulate matter right into your eyes! (Dr Periman also mentioned how the lid-lash ratio is important.)

  • People commonly fail to clean their lashes and lids when using eyelash enhancements of various kinds, because of the cost of redoing or repurchasing them, and this leads to lots of problems.

  • Watch out for the formaldehydes (among other things)

On eyelash extensions:

  • If done incorrectly, they damage the natural lashes.

  • If you have latex allergy, watch out! One of the unsuspected sources of latex may be gel pads used in the procedure.

  • They are addictive. People don’t want to wash them, because they are expensive to get redone, so debris accumulates leading to blepharitis. The debris in term breaks down the bonds and then you get them done even more frequently.

  • Lash extension cleaners are also toxic (of course).

  • (I can’t remember if this was Dr Matossian or someone during the Q&A, but someone mentioned that they always tell Lipiflow patients to stop getting extensions.)

  • Dr Periman mentioned later how blepharitis patients will often stop lid scrubs after extensions, and so their bleph gets worse.

On false eyelashes:

  • Too much glue is a big problem. (Remember, formaldehyde in the glues.)

  • They are applied 1-2mm above the lash line… exactly where baby lash grown is happening.

  • If you don’t remove them every night, you end up stripping off the new lashes.

On eyelash embellishments

I’m sure some of you saw the pictures from the Met Gala! So here is a little food for thought about what happens when you basically wire stuff onto your lashes:

  • Trauma to the lash and its roots

  • The weight leads to lash baldness

  • Some patients get allergic conjunctivitis from feathers

On LED eyelashes

Two problems - traction allopecia and the glue stripping off new growth.

On mascara

We got to see some beautifully horrific pictures of mascara buildup that actually eroded through to the conjunctiva. Yikes! Takehome: Always remove your mascara.

On lash perming, lifting and tinting

  • Lifting: Potential for chemical burns on eye surface.

  • Tinting: Vegetable based dyes are the least damaging. Tinting is often applied by people who are hair techs not eyelid specialists. Dyes must be tested on skin first in case of reactions. Patient must be upright while it’s done.

On eyelid tattoos

  • Microneedling… if too deep, it damages the meibomian glands and can lead to atrophy. Saw pictures of scary complications that would not heal.

  • Very common in Asia, and very high meibomian gland dropout rates observed.

  • Dr Periman in her later presentation mentioned a case where a tattoo salon blamed the patient. The tattoo inks even at reputable salons have lead, chromium, nickel. These things can permanently damage the MG ‘achitecture’.

On toluene allergy

  • Off-gassing from nail polish is a problem!

  • Even men with chronic blepharitis have had this traced back to their wives’ nails!

  • It doesn’t show for 3-5 days after a manicure

  • Patients get periocular hyperemia and no one connects the dots!

On jewelry implants

Ugh! You just can’t unsee these kinds of pictures:

  • Jewel implants in the white of the eye - that then caused problems

  • Glitter implanted deliberately UNDER the corneal flap created during LASIK

  • Jewel implant in the CORNEA (!)

  • An earring placed by piercing the edge of the eyelid, and which rubbed against the cornea (done in a piercing parlor)

On eye whitening procedures

I am deliberately refraining from even NAMING the whitening procedure that was mentioned at this point - and which goes under at least two different names as I just saw from the website of the physician in question (apparently it’s been re-branded, no surprises there). Why? Simply because I once had a very nasty threatening letter from a lawyer who was engaged in the process of cleansing the internet of any and all references to the AAO’s warning letter about a particular procedure offered by a particular physician (the letter was later retracted, presumably under legal pressure as well). It seems someone once posted a copy of the AAO’s letter on one of my online forums about this, and they wanted all the evidence gone once it had been retracted.

But anyway, Dr Matossian listed a number of the scarier complications associated with an eye whitening procedure, including limbal stem cell complications, infectious scleritis and scleral necrosis. Sigh. It is to be assumed that the patients experiencing those things may not have the beautiful bright white eyes today that they were hoping for, glamorous zip codes notwithstanding.

On scleral tattooing

In scleral tattooing, color is placed in the subconjunctival space. This is done by a tattoo artist who knows nothing about eye anatomy. Not surprising that it may cause issues.

DEEP BREATH!

Dr. Periman (dryeyemaster.com) on cosmetics

So now we have a problem, because at this point things sped up to about 500 mph and I simply couldn’t keep up. My notes aren’t making a ton of sense to me anymore. I probably could have taken some pictures, but at ARVO they drilled into us so incessantly that photography was verboten, that I was afraid to even appear to be aiming my phone at anything. Moving right along, it is clear to me that (1) there is a ton I need to learn about cosmetics and dry eye because hey, while I personally use almost nothing of any kind on my face, that’s not normal - these are issues that affect most women and many men - and (2) The Dry Eye Zone needs to start creating some very simple, very user-friendly resources to help people navigate information about this. Pondering how to make that happen.

Anyway, unfortunately all I can share from this part of the session are some random take-homes extracted gingerly from my scattered notes:

  • It’s not about the brand. Formulations can change at any time. You need to know about ingredients.

  • There’s an infographic that was very helpful… note to self to ask Dr Periman for it.

  • 85% of eye doctors NEVER ask about the use of cosmetics! HOW CRAZY IS THAT? Imagine the patient she discussed who came in and said “Nothing helps my dry eye!” but whose history included the following, every one of which have potential dry eye implications:

    • Brow lift

    • Abnormal lash length

    • Lash growth serum

    • Waterproof mascara

    • Harsh removers

    • Retin-A

    • Neurotoxin

    • Tatooed eyeliner

  • THE CONUNDRUM: Patients who do not remove makeup have higher dry eye symptom scores (SPEED score, specifically) but… eye makeup removers may be toxic too!

  • “Prost” ingredients eg prostaglandins bad for MGs

    • Active ingredient in lash growth serums.

    • Mentioned a particular one that advertises as prostaglandin-free but wasn’t. It was a >$100 product, not a suspicious cheap knockoff.

  • Parabens… bad for MGs and ocular surface

  • Long tables of ingredients to avoid… need to get this. Included acrylamides, alcohols, retinyls, parabens and preservatives suchas BAK, EDTA, phenoxyethanol, MIT

  • “Hypoallergenic” does not mean safe for the ocular surface.

  • “Ophthalmologist tested” really means nothing at all.

  • “Vegan, gluten-free” etc is not even remotely relevant so why advertise eye care products that way?

  • “Gems” or crushed minerals in cosmetics - what that really means is SHARDS, which can get under your lids and cause harm, but doctors cannot see them without infrared.

  • Good resource: detoxmarket.com

  • A key reason we’re in this mess, and why you might want to buy all your cosmetics while traveling abroad? The US has only 11 outlawed ingredients. Europe has 1300.

Dr Shah on botox and fillers

I didn’t get detailed notes on this one at all. I remember that initially we got a great anatomy lesson about the various eye muscles, then information on all the things Botox affects and how, from the goblet cells to the lacrimal accessory glands to the lacrimal glands to the meibomian glands, and how it can cause lid retraction, reduce meibomian gland expression, and affect basal and reflex tearing and mucin production. On the other hand, it’s used for medical treatments. Random highlights… common treatment for benign essential blepharospasm. There was a study that compared Botox to plugs! And it’s been used as a “protective ptosis” or temporary tarsorrhaphy. Another study showed post LASIK patients were happier after botox. Eventually, my eyes crossed and since I think all the Botox stuff is covered pretty well in TFOS DEWS II, I took a break and just listened.

Final take-home though - which I’ve heard often before - where they place a Botox injection is everything. I get a lot of calls from people with poor outcomes so I’m a bit sensitized to this.

On fillers, she discussed among other things hyaluronic acid gel filler for lower lid retraction. For some patients, this may be better than surgery. My takehome again was that skill matters. She presented a horrific case of a poor outcome where the injection was every so slightly off.

Dry Eye

I love the wide range of things that get studied about dry eye these days. Here are some highlights from a Saturday afternoon session on dry eye:

  • A new tear film imager from Israel (Tear Film Imager, AdOM, no regulatory approvals yet) was presented that shows all kinds of fascinating things about tear film composition and dynamics, from tear break-up, to lipid layer thickness, and from their website it sounds like they’re studying more than that as well. I love these advancing technologies… only, they’re just not likely to make it into mainstream practices. I think of all the people who could benefit from non-invasive dry eye testing.

  • Speaking of invasive dry eye testing, we saw data comparing non-invasive versus invasive TBUT testing. (Since fluorescein can destabilize the tear film, TFOS DEWS II recommends the non-invasive version of this test.) It seems fluorescein TBUT tends to be lower than the non-invasive counterpart.

  • From my neck of the woods (Seattle area), Dr Periman presented on increases in MMP9 levels (this is an indicator of inflammation) as the air quality index goes down during forest fire season.

  • Ever think about how fasting affects the tear film? With fasting for health benefits on the rise, Dr Brian Armstrong was interested enough to study the tear film during Ramadan fasting. Patients ranged in age from 23-45 (i.e. young!) and the number with positive scores on Inflammadry testing doubled during Ramadan.

  • Dr Karakus from Wilmer eye (Johns Hopkins) presented data indicating that Sjogrens patients have a higher rate of depression than non-Sjogrens dry eye patients who have a similar severity of dry eye.

  • Dr Patel presented on corneal nerve morphology and mentioned that editorial about pain (to what extent dry eye versus nerve pain) by Anat Galor that’s still sitting on my desk waiting for me to sit down with it….

  • Dr Karakus presented results of a study on the effects of prolonged reading on tear film homeostasis. An interesting point was that osmolarity decreased immediately after reading.

  • Then there were two presentations on the DREAM study. DREAM was a massively large, NIH-funded year-long very sophisticated study of the effect of Omega 3 - specifically, fish oil - on dry eye. Since it was such a large study, people will be continuing to crunch its numbers in various ways forever.

    • The first of these presenters went over the basic results, which stunned everyone last year by showing omega 3 had no more effect on dry eye than the olive oil placebo, and a couple other points like showing that omega 3 levels were not associated with dry eye symptom severity.

    • The second one noticed two interesting things about the dry eye signs vs symptoms issue: 1) Those with severe symptoms had a higher level of “discordance” between signs and symptoms - that is, it was harder to draw a line between how their eyes test and how they feel; also 2) The younger you are, the more likely there is to be a mismatch between signs and symptoms.

  • Dr Vendal presented on dry eye as a huge problem for glaucoma patients taking topical glaucoma medications. They studied 8 patients treated with Prokera, the amniotic membrane treatment, who did well. No mention, however, of which glaucoma medications or whether they were BAK preserved.

  • Then there was a fascinating presentation by Dr Zadok on ocular magnetic neurostimulation treatment for dry eye. They treated 1 eye of 9 patients, and found that it reduced staining as well as symptom scores, and patients used fewer artificial tears. They specifically mentioned a 40+yo male with Sjogrens syndrome who had had LASIK (zowie, what an awful combination) and the positive results they had.

  • Dr Holland presented current clinical results on pipeline drug KPI-121, a nanoparticle loteprednol - basically a two week low dose steroid treatment specifically for dry eye “flares”. They have a third Phase 3 trial ongoing.

  • Next up was TrueTear, the intranasal neurostimulator from Allergan. Dr Passi confirmed the results they were seeing indicated the effect is all on aqueous, not meibomian, secretion, and effects were felt up to 8 weeks after ending treatment. There were some interesting questions afterwards about the possibility of treating one side but seeing results in both sides.

  • Last presentation was about crosslinked amniotic membrane as a dressing for ocular surface disease. We’re certainly seeing more and more uses of AM in dry eye.

Dry eye at ASCRS... condensed version.

In a nutshell, of sorts….

You know it won’t be brief, because I never am. But also, bear in mind that ASCRS is about cataract and refractive surgery, beginning to end - neither of which I care about in the least… except of course as they relate to dry eye.

Following are some of my personal take-homes: highlights and impressions from the three days I spent at this very enjoyable event, partly in presentations but even more in the exhibit hall talking with companies there.

When I was at ARVO (a similarly huge but awesomely, intensively research-focused event) the previous weekend, I blogged every day. I never blogged once from ASCRS. It was partly that my days were so crammed that there was no time to spare, and partly that by the time I was one day in, my eyes were in such a state from flying and hotels and ‘convention center air’ that blogging into the wee hours was simply not an option. I arrived home after midnight Monday with stacks and stacks of notes, but also a week’s worth of work waiting for me. I figured I would start with the nutshell version first, in case I never get any further!

We need to talk beauty.

Vampire on the Vanity was the best kept secret at this conference.

“Vampire on the Vanity: Ingredients and Habits that Impact Dry Eye Disease”, by Drs Matossian, Periman and Shah was a phenomenal session. Honestly, every eye doctor treating dry eye needs to know the information they presented. I am hoping to make time this week for a blog post devoted entirely to that session so that I can get into more detail. But here are some quick highlights of the types of material they covered:

  • How your eyelashes work, what they’re there for, why that matters, and why messing with them can be a problem.

  • How lashes the wrong length or shape create a ‘wind tunnel’ directing particulate matter onto your eyes!

  • Exactly what each popular eyelash enhancement procedure does to your lashes and why you should care.

  • Everything you really, really, really did not want to know about the American cosmetic industry and what it is doing to our eyes.

    • Did you know, for example, that while Europe has banned 1300 different toxic ingredients from cosmetics, the FDA has banned (drumroll) 11?

    • Did you know that if the cosmetic product contains less than 1% concentration of an ingredient, they’re not required to disclose it at all, so you have no way to even find out what the worst possible ingredients are?

  • All about a vast array of cringeworthy eye embellishments from tattooing to jewelry implants in all kinds of surprising places to decorative items you never would have imagined, and the predictable and unpredictable damage they can cause.

  • And then a whole lot about Botox. I’ll save it for the separate blog post.

Goings-on in the MGD world

Heat & squeeze is going strong

Tons of exhibit floor space dedicated to Lipiflow, and a respectable amount for iLux, but also a noticeable presence both here and in scientific sessions from MiboFlo. In terms of heat only, there’s TearCare with their wearable thingy, and the Digital Heat Corp who have both an in-office and at-home device.

Scurf-scrubbing is holding steady

In terms of cleansing only, there was Blephex of course, and also NuLids, for whom I can’t help feeling some fondness simply because with out-of-pocket dry eye care costs skyrocketing, I want to see more compliance-friendly at-home care devices on the market rather than more and more expensive in-office procedures which are proliferating largely because we patients have amply proven that we really will pay anything for relief.

Oh, and everyone and their dog is now making or selling one of these:

A hypochlorous acid lid cleanser, a/k/a the Avenova knockoffs.

Yes, hypochlorous is the new Omega 3, that is, the newest de rigeur complement to the portfolio of any self-respecting dry eye product maker. I saw or heard tell of at least five new brand name hypochlorous acid lid ‘scrubs’ in the ASCRS exhibit hall, either just launched or coming soon, among them, TheraTears and Bruder. That’s on top of many others already on the market. I have no doubt optometrists will be private labeling them left and right before long, if they aren’t already.

Sometime soon, I need to get one of my learned friends that does not have a financial interest in any of them to explain to me for the third time, in words of as few syllables as possible, what it is that makes one hypochlorous acid product “pure” and the others “bleach-like”. But the very fact that I, who have at least a mild passing interest and one or two surviving brain cells despite my chemistry illiteracy, can’t seem to retain these facts long enough to explain them to the next person, tells me that Avenova lost that battle some time ago. I think far too many people are ignorantly happy or happily ignorant with the now ubiquitous over-the-counter versions to slow down the Avenova market share erosion.

And the MGD debates are raging

It’s not just Lipiflow, Lipiflow, Lipiflow. It’s Lipiflow vs Miboflo, Lipiflow vs Xiidra, and where is IPL in the midst exactly? The Meibomian Gland Dysfunction session on Monday was packed with study data presented on Lipiflow, Miboflo and IPL and was so interesting. I’m blogging on that separately in a bit, but a few highlights here:

  • A study claimed to show that glands really are resurrect-able with LIpiflow.

  • Another “pilot” study claimed Xiidra basically matched Lipiflow’s results in terms of improvement to both clinical signs and symptoms of dry eye.

  • 3-year results of lipiflow were presented.

  • At least three presentations remarked on improvements in cataract or refractive surgery outcomes when lipiflow is done prior to surgery.

  • 1 lipiflow was pitted against 3 miboflos 2 weeks apart, with similar results.

  • A pipeline drug is claimed to be able to clear blocked glands.

  • A miboflo study showed decent results at 90 days.

  • An IPL study examined how IPL does if you DON’T do expression (note: everyone does expression after IPL, so this was particularly interesting)

  • And another IPL study looked at 6 month results

  • Posting more details on all of these tomorrow (hopefully)

Intraductal probing felt rather conspicuously absent, but then, I don’t really know how much there has been about this at past meetings.

Don’t forget the Demodex

Dr Rosenberg presented on Demodex and the numbers were quite interesting. Most memorable: “only 1 of 82 patients with blepharitis secondary to demodex was being treated adequately”. The focus of their study was pterygium surgery patients, 83% of whom had demodex (!!).

Oh, and about the Omega 3s…

Seems like… DREAM hasn’t put a dent in anyone’s confidence in Omega 3s?

I find that so interesting.

As far as I can tell, DREAM was far and away the longest, largest, most sophisticated study ever conducted of the efficacy of fish oil for dry eye, and its conclusion was that it was no better than an olive oil placebo.

When DREAM was published, there was a brief, stunned silence, followed by a flurry of Buts and a mild storm of allegations and criticisms. Then it seems to me everyone just moved on and more or less ignored it. I taste-tested the responses from various Omega 3 purveyors in the exhibit hall and none of them ever lost their stride at all. It seems that DREAM is largely being dismissed as irrelevant. The belief that Omega 3s help dry eye is way too deeply entrenched with both patients and doctors. But I do find it interesting that DREAM hasn’t had more impact. There were two presentations about it on Saturday, but it just doesn’t seem like there is a lot of engagement. Am I missing something? Are there storms raging somewhere that I just didn’t notice? Or do we really not care?

And how about the dry eye sessions?

Random observations….

  • Tear Film Imager from Israel measures a lot of things non-invasively, including mucous layer

  • In a study of depression and dry eye, depression was a bigger problem in Sjogrens than non Sjogrens dry eye

  • A little bit about TrueTear (it would have been nice to see more than one presentation on this) - Dr Passi presented results showing benefits up to 8 weeks after use. Benefits were to aqueous production, not meibomian.

  • 30% autologous serum study that focused on patient experience: SANDE dry eye symptom scores dropped almost in half, AND all other topical medications (both prescription and over-the-counter) were decreased while using serum.

  • Klarity-C (cyclosporine 0.1% in chondroitin sulfate) - 75-patient study with endpoints of staining and OSDI - one-third of patients moved into the “normal” range of OSDI which is really pretty impressive

  • GvHD: Case report about use of amniotic membrane; patient had no symptoms for two months (wow!) then went on cyclosporine and tears, and in a recent mouse study they were able to prevent occurrence of chronic GvHD (a theme I remember from ARVO, they are trying really hard to get ahead of this and prevent acute from turning chronic by catching it earlier).

  • Presentation from Melissa Toyos on PRP drops

  • Bascom Palmer resident presenting on Botox and light sensitivity

  • Dr Donnenfeld presented results from ALG-1007. Seemed to do a great job on TBUT and staining, but questions were raised about separating the effects of the drug from the hyaluronic acid vehicle (echoes of Restasis and Endura, do you remember the days?)

  • A Rohto drop to improve the Restasis experience? Dr Epitropoulos presented results on how much better Restasis and Xiidra patients feel if they take this drop before or after. Would have been helpful to compare Rohto to some other drop, since people really do use a wide variety (at least those that know this trick to reducing the Restasis burn factor).

Corneal pain came in for a lot of attention

…even here in the LASIK mecca (10 years ago who woulda thunk)

Saturday’s dry eye session included some interesting stuff including:

  • a presentation on corneal nerve morphology and how differences in the sub nasal nerve plexus relate to dry eye symptom scores (OSDI)

  • Magnetic neurostimulation treatment

Then on Monday, we got three in a row from Bascom Palmer during the dry eye session:

  • Gabapentinoids

  • TENS

  • Nerve blockers

Pipeline drug updates

  • NOV03 - apparently doing well for evaporative dry eye patients; entering phase 3 trials this year.

  • Dextenza - This is basically a dissolvable plug used for slow release of a steroid (over the course of a month). It’s already approved for post-operative ocular pain, but they’re seeking approval for chronic allergic conjunctivitis. My interest in it is as a way to avoid BAK-preserved topical meds that cause or exacerbate dry eye.

  • OC-02 - Nasal spray for dry eye. Phase 3 trials this year.

  • KPI-121 - nanoparticle loteprednal, a low-dose steroid targeting short term relief for “dry eye flares” - their third study is ongoing

  • CycloASol - Phase Iib/III study went well, starting confirmatory trial in 2019. An interesting result presented was that reading speed improved.

  • ALG-1007, presented some results, more to come at AAO this fall

In terms of new over-the-counter drops…

Not much, but it’s mostly about HA.

Hyaluronic acid, that is. On the label, you’ll probably see it listed as sodium hyaluronate, and it will be listed in the inactive ingredients, but we all know it’s the whole point.

Everyone is either trying to do something with HA, or (for the Europeans) wishing they could somehow squish their already excellent HA products into compliance with the FDA’s antiquated monograph for over-the-counter lubricants so as to tap the lucrative US market.

Oasis, of course, beat everyone to it a long, long time ago and continue to deservedly do extremely well with Oasis Tears and Oasis Tears Plus. Some months hence we’ll be seeing a preservative-free multi-dose version of OTP, which should be very well received, although we consumers are struggling to wrap our brains around multi-dose bottles, which have a distinct learning curve and do not compare favorably to normal bottles.

But Allergan are now working their way in, with Refresh Repair, which although it was launched in a preserved version, will be coming out in preservative-free multi-dose packaging soon as well - an interesting step as it means they are leapfrogging the usual preservative free vials. Others will follow, I’m sure.

Then there’s the trehalose outlier.

TheraTears recently brought out a new drop for the first time in forever, this one with trehalose - another ingredient that Europe brought to market way before the US. Too early to have had much consumer feedback on this one yet.

Did I say something about a nutshell?

This is as brief as I can get for an event I spent three days at. There’s so much more to tell!


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.

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.

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.

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!

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!

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.

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.

Abstract

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”.

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

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.


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!

ARVO 2019.jpg

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…

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!