Tweet
Hi all,
I haven't been on the forum in so long I forgot my password! Can you believe that! But it's been a crazy year or so and the saline situation completely took over my life!
I finally wrenched myself out of the office to go to a medical meeting - TFOS 2016, my first time at the Tear Film & Ocular Surface Society's annual conference. It's been an information packed day, so much so I can hardly believe it's still just the first day.
I was going to post notes about this after the event, but there's simply far too much and if I leave it till afterwards I will never find time to go back over so many notes, so instead you're going to get a little report each day! Here's the first installment:
DAY 1
SEX AND GENDER
Janine Clayton of the NIH’s Office of Research on Women’s Health opened the conference with a compelling talk on the necessity of considering sex as a biological variable at every stage of research beginning with the most basic cellular research. She included cases (covering areas of medicine such as myocardial infarction) where a drug improved outcomes for men but worsened outcomes for women, mentioned that 8 out of 10 drugs withdrawn by the FDA had different effects in women than men, and gave persuasive reasons to believe that attention to sex is crucial in eyecare specifically.
John Cidlowski of NIH/NIEHS Signal Transduction Laboratory (the only member of his institute working on eyes, incidentally) presented absolutely fascinating research on glucocorticoids (the part of our cells that steroids act on) and the dramatic differences between females and males, for example, as in a rat study where steroids induced more repression of gene expression in the males and more induction of gene expression in females. His lab has just recently gotten approval for some human studies. He feels that ophthalmologists have historically been in a rush to employ steroids and that research is still "catching up", and suggested that there ought to be different corticosteroids developed for men vs women. (Maybe in another 10 years?) Hopefully pharmaceutical companies are listening.
David Sullivan (conference director, of Schepens Eye, Mass Eye & Ear, Harvard). Of all the talks I really wanted good notes on, I have almost nothing! I type very quickly but… not quickly enough for this. From intracrinology to premature ovarian failure to androgen decreasing keratinization, it all zipped by - the schedule was running behind and, to keep us on schedule, he sped up from his naturally brisk pace out of courtesy to the other speakers and the poster presenters. David is always brilliant and fascinating and I will see if I can nab a copy of the presentation to report more.
FRICTION
Tannin Schmidt from the University of Calgary’s Faculty of Kinesiology and Schulich School of Engineering talked about friction, lubrication and wear, introducing us to the science of biotribology (study of friction) and its immediate relevance to lubricants for the ocular surface center, focusing on PRG4, aka Lubricin, aka the (relatively) new promising drug to watch through clinicals. Tannin was followed up by Heiko Pult of Optometry & Vision Research, Weinheim, Germany with more about blinking and biotribology. I confess he lost me thoroughly somewhere in the technical details about hydrodynamic effects under all different velocities and speeds. Finally, Ben Sullivan of TearLab gave us a talk on hyperosmolarity and the mechanisms by which it affects the ocular surfaces and related matters. He made some interesting statements about the role of the corneal epithelium in tear evaporation (as opposed to the meibomian gland secretions which tend to get all the focus) and looked at how hyperosmolarity relates to Restasis and other common treatments. His bottom line (as I understood it) was that hyperosmolarity needs to be treated, independent of other signs. Lubricin of course came in for plenty of attention in this talk as well.
DEBATES
After lunch there was a debate among some participants about techniques of stem cell treatments for limbal stem cell deficiency, and while I find LSCD interesting, it wasn't particularly relevant to dry eye as we know it so I did not keep notes on it.
This was followed by a rather more colorful debate between a husband-wife team, Kelly Nicholsand Jason Nichols (University of Alabama, Birmingham, and lead authors on TFOS' reports on, respectively, Meibomian Gland Dysfunction and Contact Lens Discomfort) about which is the greater risk factor for dry eye: MGD or CLD. This included plenty of solid data as well as tongue in cheek elements - or as Kelly would have it, one of them had good jokes and the other real data. In the end we seemed to have concluded that, once again, it really is hard to tell chickens from eggs.
NEUROPATHIC PAIN
Next up was a subject we are all no doubt very keen on: neuropathic pain.Elizabeth Felix (University of Miami, Miller School of Medicine) started this section off with excellent background information defining pain, differentiating between nociceptive pain and neuropathic pain and discussing the difficulties of trying to diagnose it; also introduced the subject of QST (quantitative sensory testing). Note to self to look up a 2008 study’s flowchart on diagnosis, and to ask her about a list of screening tools on a slide that flickered past too quickly. Carlos Bellamonte, chair of DEWS II’s neuropathic pain subcommittee (Neuroscience institute, Alicante, Spain), picked up from there. At this point I’m afraid my body reminded me that I’d had about 3 hours or so of sleep over the previous 72 hours, and while the food here is absolutely fantastic, the coffee, well, I really needed a painfully American giant dose rather than the (I kid you not) thimblefuls available during the coffee/poster session… result, long before the 300th mention of the word receptors I was nodding off (no reflection on the speaker). Anat Galor (U of Miami / Miller as well I believe?)woke me up though with her practical discussion of diagnosis and management. She pointed out ophthalmologists’ reluctance to use the word “pain” in a dry eye context - typically preferring “discomfort” - while given the actual definition of pain*, embracing the term “pain” openly is more appropriate. She talked about the extent to which using standardized metrics is helpful and explained that neuropathic pain can be a clinical description or a diagnosis - but if the latter (actual diagnosis) it requires a lesion or a disease, so more often it comes down to clinical judgment, especially since clinical signs aren’t necessarily consistent. She encouraged listeners to consider the possibility of neuropathic pain whenever there is pain in spite of a relatively good ocular surface.
* “An unpleasant sensory and emotional experience associated with actual or or potential tissue damage or described in terms of such damage.”
WORLD/REGIONAL REPORTS
The next section was individuals reporting on unique needs and challenges of ocular surface disease in various parts of the word. Geetha Iyer of India described some of their challenges with acid violence cases and high rates of Stevens Johnson syndrome. Kovin Naidooreported on challenges of getting any resources for ocular surface diseases in Africa given the greater focus on other health crises from HIV/AIDS to cataracts. Jose Gomes presented on ocular surface challenges specific to Latin America including things like leprosy and trachoma in northern regions of Brazil, and also reported results from the Brazilian Amazon Region Eye Survey, and impressive achievement of to reach some of the most world’s most inaccessible populations. Jenny Craig reported on challenges in Oceania where geography, poverty and culture impede provision of any eyecare at all in many locations. Finally Stefano Bonini discussed a completely different world of challenges - in Europe, the difficulties of trying to get new therapies developed and through the regulatory approval process successfully. Separately, he pointed out the need for simple, practical suggestions that can help general ophthalmologists improve diagnosis and treatment of dry eye patients, which I thought was an excellent point. Trivia: Did you know the cornea has 7,000 nerve endings per square millimeter? (No wonder it hurts.)
POSTER SESSION #1
I took pictures of a number of posters I was interested in but my eyes are not quite up to the squinting just now. Notes here on just one and hopefully I’ll get to the others tomorrow:
Refractive surgery: An excellent study from Korea comparing 40 LASIK patients, 40 PRK patients and 80 controls. Of those who had refractive surgery, they were examined an average of 4 (for PRK) or 6 (for LASIK) years after surgery. Dry eye disease and/or MGD proportions were 60% (LASIK), 42.5% (PRK) and 26.2% (controls). OSDI score averages of 27% (LASIK), 20% (PRK) and 10% (controls). Other findings which were similarly worse for LASIK, and less so but still significantly worse than control for PRK, included: staining, lid margin abnormality, meibomian gland expressibility and meibum quality.
INNOVATION SHOWCASE
First time they’ve done this at TFOS… invited several small companies with new product innovations seeking investment. Moderated by Toby Stone (EyeFocus, accelerator type co) with great questions posed by a panel of pharmaceuticals (Shire, Allergan, Alcon) and David S. Some of the questions I most appreciate were, if you removed the terminology parts, along the lines of "But does it actually work if your eyes are dry?" Sounds like a no-brainer, but it isn't, for example, David asked the OptimEyes folks how their delivery 'platform', which attaches to the mucous layer, would work if the mucous itself is compromised (as it so often is in some types of dry eye).
Avizorex Pharma(Barcelona based biotech) presented about secretagogue AVX-012. Reportedly promotes tear film stability by improving blink rate and basal tear production. Clinical trial application submitted in Spain.
Cambium Medical Technologies is developing ELATE OCULAR, a “standard commercialized regulatory approved allogeneic shelf stable reimbursable platelet rich plasma serum drop” - in other words serum as a commercial product! Most exciting if they can pull off what they claim! They have a 2 step plan of approach - first fast track it as an orphan drug for a single indication (GvHD), then pursue approval for moderate to severe dry eye. They have a strategic partner and are planning to file IND in 1Q2017.
Mu-Drops (Netherlands) is developing a manufacturing system for blood banks to prepare “micro-serum” drops (i.e. dispensed in far smaller doses than conventional drops), in the Netherlands initially but they plan to approach sources elsewhere in Europe as well. They say they can get 1,750 doses (undiluted) from a single donation, dramatically reducing inconvenience (& cost?) to patients. This is capitalizing on the well established but relatively little advertised fact that the eye surface can only take a fraction of an actual normal drop size. They will have something in the poster session tomorrow so I’ll report more after I see that.
Opia Technologies is developing a new tear sampling device (TearPrim) to complement their existing product (EyePrim) for dry eye diagnostics. They claim it collects 50% more cells than other methods. Confession: I was too distracted with serum excitement to listen to all the details (not that there were that many).
20/20 OptimEyes has developed a “mucoadhesive micelle drug delivery platform for controlled, sustained, targeted delivery”. It’s a long story but the bottom line is this: imagine that burn of Restasis just once every week or two rather than twice (at least) daily. They are targeting the platform first for cyclosporine-A but also are looking beyond eyes to many other applications.
TearSolutionsis focusing their LacriPep (lacritin) drug on the Sjogrens Syndrome application and raising capital to take it into Phase I/II clinicals. They are presenting posters tomorrow as well.
A little aside: After unceremoniously booting Shire (aka Xiidra aka the Jennifer Aniston dry eye drug) reps from the clearly labeled patients-only DryEyeTalk Facebook group, I have to backpedal slightly and state that a Shire staffer saved my life this morning by handing me a handful of refresh plus vials… my eyes were killing me from the A/C and I suddenly realized I had brought nothing with me, nothing, and it was 9 in the morning.... My hotel is a 20 minute walk away and the schedule was jam packed. So kind of her to share. I don’t even know her name, but whoever you are, thank you!
That's all for today.
I haven't been on the forum in so long I forgot my password! Can you believe that! But it's been a crazy year or so and the saline situation completely took over my life!
I finally wrenched myself out of the office to go to a medical meeting - TFOS 2016, my first time at the Tear Film & Ocular Surface Society's annual conference. It's been an information packed day, so much so I can hardly believe it's still just the first day.
I was going to post notes about this after the event, but there's simply far too much and if I leave it till afterwards I will never find time to go back over so many notes, so instead you're going to get a little report each day! Here's the first installment:
DAY 1
SEX AND GENDER
Janine Clayton of the NIH’s Office of Research on Women’s Health opened the conference with a compelling talk on the necessity of considering sex as a biological variable at every stage of research beginning with the most basic cellular research. She included cases (covering areas of medicine such as myocardial infarction) where a drug improved outcomes for men but worsened outcomes for women, mentioned that 8 out of 10 drugs withdrawn by the FDA had different effects in women than men, and gave persuasive reasons to believe that attention to sex is crucial in eyecare specifically.
John Cidlowski of NIH/NIEHS Signal Transduction Laboratory (the only member of his institute working on eyes, incidentally) presented absolutely fascinating research on glucocorticoids (the part of our cells that steroids act on) and the dramatic differences between females and males, for example, as in a rat study where steroids induced more repression of gene expression in the males and more induction of gene expression in females. His lab has just recently gotten approval for some human studies. He feels that ophthalmologists have historically been in a rush to employ steroids and that research is still "catching up", and suggested that there ought to be different corticosteroids developed for men vs women. (Maybe in another 10 years?) Hopefully pharmaceutical companies are listening.
David Sullivan (conference director, of Schepens Eye, Mass Eye & Ear, Harvard). Of all the talks I really wanted good notes on, I have almost nothing! I type very quickly but… not quickly enough for this. From intracrinology to premature ovarian failure to androgen decreasing keratinization, it all zipped by - the schedule was running behind and, to keep us on schedule, he sped up from his naturally brisk pace out of courtesy to the other speakers and the poster presenters. David is always brilliant and fascinating and I will see if I can nab a copy of the presentation to report more.
FRICTION
Tannin Schmidt from the University of Calgary’s Faculty of Kinesiology and Schulich School of Engineering talked about friction, lubrication and wear, introducing us to the science of biotribology (study of friction) and its immediate relevance to lubricants for the ocular surface center, focusing on PRG4, aka Lubricin, aka the (relatively) new promising drug to watch through clinicals. Tannin was followed up by Heiko Pult of Optometry & Vision Research, Weinheim, Germany with more about blinking and biotribology. I confess he lost me thoroughly somewhere in the technical details about hydrodynamic effects under all different velocities and speeds. Finally, Ben Sullivan of TearLab gave us a talk on hyperosmolarity and the mechanisms by which it affects the ocular surfaces and related matters. He made some interesting statements about the role of the corneal epithelium in tear evaporation (as opposed to the meibomian gland secretions which tend to get all the focus) and looked at how hyperosmolarity relates to Restasis and other common treatments. His bottom line (as I understood it) was that hyperosmolarity needs to be treated, independent of other signs. Lubricin of course came in for plenty of attention in this talk as well.
DEBATES
After lunch there was a debate among some participants about techniques of stem cell treatments for limbal stem cell deficiency, and while I find LSCD interesting, it wasn't particularly relevant to dry eye as we know it so I did not keep notes on it.
This was followed by a rather more colorful debate between a husband-wife team, Kelly Nicholsand Jason Nichols (University of Alabama, Birmingham, and lead authors on TFOS' reports on, respectively, Meibomian Gland Dysfunction and Contact Lens Discomfort) about which is the greater risk factor for dry eye: MGD or CLD. This included plenty of solid data as well as tongue in cheek elements - or as Kelly would have it, one of them had good jokes and the other real data. In the end we seemed to have concluded that, once again, it really is hard to tell chickens from eggs.
NEUROPATHIC PAIN
Next up was a subject we are all no doubt very keen on: neuropathic pain.Elizabeth Felix (University of Miami, Miller School of Medicine) started this section off with excellent background information defining pain, differentiating between nociceptive pain and neuropathic pain and discussing the difficulties of trying to diagnose it; also introduced the subject of QST (quantitative sensory testing). Note to self to look up a 2008 study’s flowchart on diagnosis, and to ask her about a list of screening tools on a slide that flickered past too quickly. Carlos Bellamonte, chair of DEWS II’s neuropathic pain subcommittee (Neuroscience institute, Alicante, Spain), picked up from there. At this point I’m afraid my body reminded me that I’d had about 3 hours or so of sleep over the previous 72 hours, and while the food here is absolutely fantastic, the coffee, well, I really needed a painfully American giant dose rather than the (I kid you not) thimblefuls available during the coffee/poster session… result, long before the 300th mention of the word receptors I was nodding off (no reflection on the speaker). Anat Galor (U of Miami / Miller as well I believe?)woke me up though with her practical discussion of diagnosis and management. She pointed out ophthalmologists’ reluctance to use the word “pain” in a dry eye context - typically preferring “discomfort” - while given the actual definition of pain*, embracing the term “pain” openly is more appropriate. She talked about the extent to which using standardized metrics is helpful and explained that neuropathic pain can be a clinical description or a diagnosis - but if the latter (actual diagnosis) it requires a lesion or a disease, so more often it comes down to clinical judgment, especially since clinical signs aren’t necessarily consistent. She encouraged listeners to consider the possibility of neuropathic pain whenever there is pain in spite of a relatively good ocular surface.
* “An unpleasant sensory and emotional experience associated with actual or or potential tissue damage or described in terms of such damage.”
WORLD/REGIONAL REPORTS
The next section was individuals reporting on unique needs and challenges of ocular surface disease in various parts of the word. Geetha Iyer of India described some of their challenges with acid violence cases and high rates of Stevens Johnson syndrome. Kovin Naidooreported on challenges of getting any resources for ocular surface diseases in Africa given the greater focus on other health crises from HIV/AIDS to cataracts. Jose Gomes presented on ocular surface challenges specific to Latin America including things like leprosy and trachoma in northern regions of Brazil, and also reported results from the Brazilian Amazon Region Eye Survey, and impressive achievement of to reach some of the most world’s most inaccessible populations. Jenny Craig reported on challenges in Oceania where geography, poverty and culture impede provision of any eyecare at all in many locations. Finally Stefano Bonini discussed a completely different world of challenges - in Europe, the difficulties of trying to get new therapies developed and through the regulatory approval process successfully. Separately, he pointed out the need for simple, practical suggestions that can help general ophthalmologists improve diagnosis and treatment of dry eye patients, which I thought was an excellent point. Trivia: Did you know the cornea has 7,000 nerve endings per square millimeter? (No wonder it hurts.)
POSTER SESSION #1
I took pictures of a number of posters I was interested in but my eyes are not quite up to the squinting just now. Notes here on just one and hopefully I’ll get to the others tomorrow:
Refractive surgery: An excellent study from Korea comparing 40 LASIK patients, 40 PRK patients and 80 controls. Of those who had refractive surgery, they were examined an average of 4 (for PRK) or 6 (for LASIK) years after surgery. Dry eye disease and/or MGD proportions were 60% (LASIK), 42.5% (PRK) and 26.2% (controls). OSDI score averages of 27% (LASIK), 20% (PRK) and 10% (controls). Other findings which were similarly worse for LASIK, and less so but still significantly worse than control for PRK, included: staining, lid margin abnormality, meibomian gland expressibility and meibum quality.
INNOVATION SHOWCASE
First time they’ve done this at TFOS… invited several small companies with new product innovations seeking investment. Moderated by Toby Stone (EyeFocus, accelerator type co) with great questions posed by a panel of pharmaceuticals (Shire, Allergan, Alcon) and David S. Some of the questions I most appreciate were, if you removed the terminology parts, along the lines of "But does it actually work if your eyes are dry?" Sounds like a no-brainer, but it isn't, for example, David asked the OptimEyes folks how their delivery 'platform', which attaches to the mucous layer, would work if the mucous itself is compromised (as it so often is in some types of dry eye).
Avizorex Pharma(Barcelona based biotech) presented about secretagogue AVX-012. Reportedly promotes tear film stability by improving blink rate and basal tear production. Clinical trial application submitted in Spain.
Cambium Medical Technologies is developing ELATE OCULAR, a “standard commercialized regulatory approved allogeneic shelf stable reimbursable platelet rich plasma serum drop” - in other words serum as a commercial product! Most exciting if they can pull off what they claim! They have a 2 step plan of approach - first fast track it as an orphan drug for a single indication (GvHD), then pursue approval for moderate to severe dry eye. They have a strategic partner and are planning to file IND in 1Q2017.
Mu-Drops (Netherlands) is developing a manufacturing system for blood banks to prepare “micro-serum” drops (i.e. dispensed in far smaller doses than conventional drops), in the Netherlands initially but they plan to approach sources elsewhere in Europe as well. They say they can get 1,750 doses (undiluted) from a single donation, dramatically reducing inconvenience (& cost?) to patients. This is capitalizing on the well established but relatively little advertised fact that the eye surface can only take a fraction of an actual normal drop size. They will have something in the poster session tomorrow so I’ll report more after I see that.
Opia Technologies is developing a new tear sampling device (TearPrim) to complement their existing product (EyePrim) for dry eye diagnostics. They claim it collects 50% more cells than other methods. Confession: I was too distracted with serum excitement to listen to all the details (not that there were that many).
20/20 OptimEyes has developed a “mucoadhesive micelle drug delivery platform for controlled, sustained, targeted delivery”. It’s a long story but the bottom line is this: imagine that burn of Restasis just once every week or two rather than twice (at least) daily. They are targeting the platform first for cyclosporine-A but also are looking beyond eyes to many other applications.
TearSolutionsis focusing their LacriPep (lacritin) drug on the Sjogrens Syndrome application and raising capital to take it into Phase I/II clinicals. They are presenting posters tomorrow as well.
A little aside: After unceremoniously booting Shire (aka Xiidra aka the Jennifer Aniston dry eye drug) reps from the clearly labeled patients-only DryEyeTalk Facebook group, I have to backpedal slightly and state that a Shire staffer saved my life this morning by handing me a handful of refresh plus vials… my eyes were killing me from the A/C and I suddenly realized I had brought nothing with me, nothing, and it was 9 in the morning.... My hotel is a 20 minute walk away and the schedule was jam packed. So kind of her to share. I don’t even know her name, but whoever you are, thank you!
That's all for today.
Comment