The Latest Dope
Editor's note: We can't possibly cover everything that's happened in the last six months (eeps, is it really that long since we put out a fresh newsletter?), so this is a bit of a random collection. Enjoy.
THE FIRST ANNUAL SAFETY HARBOR DRY EYE SYMPOSIUM was quietly held on February 17-19 at the Safety Harbor Resort & Spa (near Tampa, FL). We won't attempt to describe it other than to say that it was altogether unique and, judging from the feedback from patients and speakers, a resounding success. We'll let you know when dates are set for next year's. We make no secret of the fact that one of our modest ambitions in undertaking patient education events like this is to goad the industry into offering the public more real education amid the infomercials.
SLEEPING WITH YOUR EYES OPEN? Dr. Latkany's excellent overview and classification of nocturnal lagophthalmos in the January issue of The Ocular Surface (Vol 4, No 1) should be required reading. Seriously. Amid all the exciting pharmacological and surgical developments in ocular surface disease, we fear that the more mundane basics from eyelid mechanics to meibomian glands are getting, at best, lip-service rather than proper clinical investigation and treatment. Click here and scroll down for a brief summary. But you really need to get hold of the full article and read the whole thing or at least sections V and VII.
A CHEEKY NEW TWIST ON AMT? In February's AJO, Inatomi et al reported results of a complex ocular surface reconstruction technique designed for severe cases such as Stevens-Johnson patients. The general idea is to redeploy stem cells from the mouth in the eye; materials included amniotic membrane, oral mucosa and (in some cases) autologous serum. See "Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation", Am J Ophth 2006;141:267-275 (click here for abstract - and if you subscribe, see also Scheffer Tseng's excellent background article on pp. 356-7).
SPEAKING OF AMT, AN UPDATE ON THE NON-SURGICAL FRONT: A small case series presented by Parmar et al in February's AJO about AMT applied with a collagen corneal shield and supported by a soft contact sounds very promising, showing good safety and efficacy with in fact complete resolution of persistent epithelial defects in the three eyes studied. See "Ocular surface restoration using non-surgical transplantation of tissue-cultured human amniotic epithelial cells", Am J Ophth 2006;141:299-307 (click here for abstract). We are looking forward to seeing more.
STILL PLUGGING AWAY: A study in January's Cornea (Atelocollagen punctal occlusion in dry eye patients, Miyata et al, Cornea 2006;25:47-50, click here for abstract) found atelocollagen plugs to improve ocular surface disorders for up to 8 weeks after insertion. It also nicely summed up concerns about problems associated with other types of plugs, such as extrusion, migration, infection and discomfort. Meanwhile, a brief report in February's AJO (Clinical evaluation of the Smart Plug (TM) in the treatment of dry eyes, Kojima et al, AmJ Oph 2006;141:386-388) confirmed our main concern with these otherwise attractive (e.g. easy to insert, very comfortable) plugs: We still don't know where the heck they go once they're in. Out the other end three days later? Or some indeterminate location where they partially block tears without much altering Schirmer scores? Click here for abstract.
IF NO NEWS IS GOOD NEWS, WHAT IS NEWSLESS NEWS? In an unprecedentedly content-rich press release, we learned the other day that Inspire had a meeting with the FDA in which they discussed providing further information to the FDA in order to discuss how to have further discussions about diquafosol. Not that we've been holding our breaths or anything. Don't bother clicking here for press release.
MUCINS, MEIBOMIANS AND MORE: We found this fascinating, despite the content being at a level you might expect when co-authors include six PhDs: "The surface activity of purified ocular mucin at the air-liquid interface and interactions with meibomian lipids", Millar et al, Cornea 2006;25:91-100 (click here for abstract). On a side note, fans of sodium hyaluronate tears might be interested to see these authors' findings about surface activity of hyaluronic acid and its relevance to use of HA in tears.
AND IF YOU CAN STOMACH AN AVERAGE OF 16 SYLLABLES PER WORD, this study of “dry eye” in terms of mucosal immune regulation is quite interesting. (Mucosal Immunity and Self-Tolerance in the Ocular Surface System, Austin K. Mircheff, PhD et al, The Ocular Surface; 2005;4:182-193 Vol 3: No 4.) In terms of implications for therapy, it discusses systemic hormonal replacement, local gene transfer therapy, and cellular immunotherapy. Click here for article.
BUT HERE IS WHERE WE DRY THE LINE (REALLY): As a matter of principle your editor flatly refuses to read and summarize studies whose titles extend half a page vertically. Nevertheless, being personally acquainted with individuals suffering severe epiphora she is loathe to pass over a study that might be relevant and hereby refers the inquisitive amongst us to Parts I and II of a study about lacrimal duct obstruction by Sasaki et al in December AJO. Click here for the first abstract and here for the second.
LANGUAGE BUFFS might enjoy Juan Murube’s meanderings through language history, even if it does perhaps get a teensy bit too ambitious in its scope: “Etymology of the Term ‘Tear’, The Ocular Surface; 2005;4:177-181 Vol 3: No 4. If you ever wondered what “tear” is called in Albanian, Old Irish or Frisian, now’s your chance. Click here for full article.
BLOODY GOOD FOR LASIKED BUNNIES: In November's Cornea Esquenazi et al reported on some interesting work with autologous serum to treat post LASIK epithelial defects in rabbits. "Use of autologous serum in corneal epithelial defects post-lamellar surgery", Cornea 2005;24:992-997, click here for abstract.
WHAT TAKES 3 YEARS LONGER FOR A LASIK PATIENT THAN A PRK PATIENT? Recovery of subbasal nerve density, according to a study in the December issue of AJO. In "Recovery of corneal subbasal nerve density after PRK and LASIK" (J. Erie MD et al, Am J Oph 2005;140:1059-1064, click here for abstract) it took 2 years after PRK and 5 years after LASIK for nerve density to recover to near preoperative levels.
OF FORESTS, TREES, LASERS AND DRY EYES: Don't miss "The incidence and risk factors for developing dry eye after myopic lasik", Cintia de Paiva MD et al, Am J Oph 2006;141:438-445 (click here for abstract). The ink was probably still wet when the arguing began about the definition of dry eye, the relevance of corneal staining, and the price of legumes in large Asian countries. We dare to opine that a conclusion of "Dry eye occurs commonly after LASIK surgery in patients with no history of dry eye....", supported by numbers like "36.36% at 6 months" and with names like Pflugfelder and Koch wafting through the credits, speaks for itself, and describes a forest more interesting for its sheer acreage than its leaf veining patterns. Somebody in December's JCRS seems to be on that page too: "The grittiness, burning sensation, ocular irritation, foreign-body sensation, photophobia, diplopia, and fluctuation of vision with blinking that are associated with dry eyes have been frequently reported after LASIK" (Chen et al, "LASEK for dry eye associated with soft contact lenses", J Cat Refr Surg 2005;31:2299-2305, click here for abstract.) But the inspiring faith that has long characterized the practice of LASIK will no doubt prevail over the ravings of us skeptics. Adeste fideles, perscribamus restasis.
What’s in the pipeline?
Phase III clinical trials (or thereabouts)
OTSUKA-NOVARTIS/REBAMIPIDE: Phase III clinical trials ongoing. This seems to be the furthest along of anything in the current pipeline, but there is no news and little gossip to report since our last update. We've heard some modestly positive reports. Click here for initial screening checklist and list of study centers. Participants receive higher or lower dose or placebo.
NOVAGALI/NOVA22007: Expecting to start Phase III trials in 2006, having announced completion of Phase II in January which reportedly demonstrated safety and "trends towards efficacy". What is it? Cyclosporine emulsion. Click here for press release. *April 12 update: Per Novagali press release they are in Phase III now, and have new funding.
NASCENT/ iDESTRIN (NP50301): Phase IIb clinical completed. Latest report was in early January (click here for press release) stating good results from Phase IIb with "no drug related serious adverse effects". What it is: Topical ophthalmic therapeutic eye drop for treating dry eye in postmenopausal women.
SENJU-ISTA/ECABET SODIUM: Expecting to start Phase III trials in 2007, having reported positive results from Phase IIb studies in February 06. Ista claim that this is the first drug to show efficacy in clinicals against both signs and symptoms of dry eye. What is it? Mucin secretagogue. Click here for most recent press release.
Phase II or I
NOVARTIS / PIMECROLIMUS (AMS981): Recruiting for Phase II clinicals. Click here for more info (or patients interested in signing up click here).
LANTIBIO/MOLI1901: Currently undergoing Phase II trials in the US following positive results in european Phase I studies. Click here for a, uh, colorful graphic about the mechanism of action. What is it? Cystic fibrosis drug being attempted as a dry eye treatment.
ALLERGAN/ANDROGEN TEARS: Alive but not visibly kicking. Some Phase IIs had been completed (data to be presented at ARVO). Grapevine says that Allergan will be restarting some new trials before long. We are anxious to see this on the market considering many positive reports from doctors and patients, but thus far it seems to be on a slow boat headed nobody knows quite where. We'll post updates if we get any new info.
Dumb, dormant, defunct or dead
INSPIRE/DIQUAFOSOL: Expect them to announce whether or not they've opted for DNR "by the end of April 2006". Click here for Inspire's inspiring page about diquafosol.
ALCON/15-HETE: We haven't read an obit yet, but neither have we seen any signs of life or resuscitation teams in a year or so.
(Obit) SUCAMPO/TACROLIMUS: Sucampo announced last June that despite completion of Phase II safety and efficacy study, it was voluntarily suspending its tacrolimus eye drops development program because of FDA safety concerns about Protopic®, a prescription cream for treating atopic dermatitis marketed by Astellas Pharma, Inc. Click here for press release.
Have we missed anything? Email it to us at email@example.com.
In the spotlight this issue
BOSTON SCLERAL LENS
Mark Cohen, Executive Director of the Boston Foundation for Sight, was kind enough to be a guest speaker at our Safety Harbor dry eye symposium in February. While we already knew some dry eye patients who had benefitted from sclerals, Mark's presentation and Q&A was as illuminating as it was impressive, as it dispelled many of our misconceptions about the device and revealed very impressive success rates.
Some of the aspects of the work being done at BSF that are most interesting to us at this time and which motivate us to seek to raise awareness about this treatment modality include (a) successful use of the lens in dry eye patients whose quality of life has been dramatically impacted by their symptoms but who do not present with the extreme clinical signs traditionally associated with advanced corneal disease, and (b) its use as a prophylactic device to prevent patients with chronic ocular surface disease from reaching the point where they would require corneal transplantation.
For patients who are unfamiliar with sclerals and how they are used in dry eye, we provide answers to a few frequently asked questions below. For physicians who are aware of sclerals but have never considered them an option for a patient of their own with advanced corneal disease, we would like to encourage you to contact the Foundation for information about the wide variety of patients accepted for treatment.
A few brief Q&A for patients:
WHAT IS A SCLERAL LENS? A scleral lens is a very large gas permeable lens. It does not touch the cornea (central, sensitive clear covering of the eye) at all, and therefore does not hurt, move around or stick the way a normal gas perm lens might. Instead, the edges rest on the tougher sclera (white of the eye).
WHAT IS IT FOR AND HOW DOES IT WORK? The purpose of the scleral lens is to provide a sort of liquid bandage for your cornea. Each time you put the lens in, you first fill it up with artificial tears and then put it on the eye. So the lens is basically holding a resevoir of fluid over your eye all day long, which will reduce pain and light sensitivity and improve vision.
HOW BIG IS IT? About the size of a quarter.
DO I WEAR IT 24X7? No, normally you would only wear it during the day.
CAN MY OWN EYE DOCTOR ORDER SCLERALS FOR ME? No, scleral lenses have to be individually designed for your eyes by specialists.
Patients, for answers to many more questions about sclerals, please visit this link or contact BSF.
DOCTORS AND PATIENTS, for further information please visit www.bostonsight.org or contact the Boston Foundation for Sight (Telephone (781)-726-7337 or email firstname.lastname@example.org).