Allergan, dearest, you have really outdone yourselves this time

By unamimous vote of the membership of Dry Eye Talk, the prestigious Cheesiest Pharmaceutical Marketing Effort of the Year award goes to whoever in Allergan's marketing department came up with an idea which if it weren't so simply demented would be even more offensive:

The Dry Eye Book Club.

Read it and weep.

Honestly... sponsoring someone to write a tear-jerker as a way to "raise disease awareness" (a/k/a sell more drugs)?

Inviting people to join "The Dry Eye Book Club" - and when they click on the link, redirecting them to registration for the Optive Frequent Buyer program - which includes requirements like joining all the marketing lists?

I simply could not believe this when I saw it. I think if our members weren't so darned desperate, some of them would be throwing away their Restasis in protest.

Seriously, Allergan, if anyone out there is listening, here are just a few of my personal objections to this ad:

1. The whole idea insults the intelligence of the average human being and especially women.

2. If you're going to put a human face on dry eye, make them at least pretend to have REAL dry eye. It's an insult to the rest of us to suggest that someone whose most serious complaint is that she uses artificial tears "up to 5 times a day" suffers from chronic dry eye. For heaven's sakes, our DryEyeZone members would give their right hand to be able to survive on 5 artificial tear doses. Many use audio books because they can no longer read - tear-jerkers or otherwise.

3. Artistic license is fine in marketing but let's not stray quite that far from medical facts! We all know that the reflex type tears that we get from irritants or emotion are different from the balanced basal tears we so desperately need.

4. Choosing as the professional face for this ad a physician best known as a pioneer in refractive surgery... er... no offense whatsoever to Dr. McDonald who enjoys an excellent reputation, but A, did it never occur to you HOW some of us got our dry eyes?

Please, please scrap this nonsense and go back to classic infomercials.

Industry news/gossip: Restasis inventor lashes out

This tidbit reaches way back into the past of Restasis, when a professor at the University of Georgia first put cyclosporin into a solution to treat canine dry eye 20+ years ago.... Now that Restasis is a blockbuster drug for Allergan, there is some unhappiness out there about how the university where it all started has shortchanged itself and the inventor of the longterm rewards.

UGA research royalty deal sours

...UGA officials expect royalty and licensing income to set yet another record next year, mainly because of a $10 million payment due from the global pharmaceutical company Allergan....

But the research foundation's payments from the pharmaceutical company would be millions more if inexperienced UGA officials had not caved in to tougher negotiators from the drug company, according to the former UGA faculty member whose invention provided the basis for Restasis....

More than two decades ago, [Renee] Kaswan thought of something no one had tried before - putting the immunosuppressant drug cyclosporin into a solution so that it could be applied to the eyes of dogs suffering from dry eye....

Kaswan's second idea was even bigger than Optimmune, the dog dry eye drug. Why not use basically the same solution to cure dry eye in humans?

The U.S. Food and Drug Administration approved the new drug for human use in 2002. And in 2003, Allergan began marketing and selling the drug, which it called Restasis....

New product: Tranquileyes "stye care kit"

"Stye care kit" a/k/a single-eye Tranquileyes....

Click for details or to purchase in The Dry Eye Shop

What it is

This is Eye Eco's latest twist on the Tranquileyes theme. Here's what the kit consists of:
- One Tranquileyes eyecup
- Eye cushion and moisture pad (unlined type)
- Two Thermoeyes heat inserts
- Simple elastic band to hold eyecup on
- Mesh washbag for the moisture pad

How it's used

First, if you're new to Tranquileyes and Thermoeyes, I suggest you read up on both first.

The new twist here is using the thermoeyes on top of the moisture pad rather than underneath, so as to apply heat directly to the eyelid. Of course, some few of you are already doing this, with or without the goggle, because it's the only non-microwave, multi-use heat device available and suitable (so far as I know... let me know if there's any hidden gems out there I haven't heard of).

This was packaged specifically with styes in mind BUT I think there will be a variety of applications for them. Here are a few suggestions just off the top of my head:

Stye treatment (that's what the directions in the kit are for): Use the heat insert on top of the moisture pad. Since it has the regular (thick) moisture pad instead of a thermopad, this will put more pressure on the lid and hold the heat right where you want it.

Meibomian gland dysfunction, one eye at a time: What this single-eye kit will allow you to do is multitask... do heat on one eye while you're using the other eye.

Daytime rejuvenation, one eye at a time: Do your eyes get more and more painful as the day progresses? For a lot of people, giving your eyes a 20-30 minute break at some point during the day can make a huge difference - set the clock back, so to speak - and many use the tranquileyes goggle for that purpose. But not everybody can afford that much "downtime". If you're in an environment where you don't mind being seen with this, it would allow you to give one eye a moisturizing break while you continue working or doing other things. Then just switch eyes....

Night protection for a single eye. Now mind, I have not tried this myself so I cannot attest to how well it will stay on if you're tossing and turning. Usually if people only need to treat a single eye, I suggest that they get the full goggle and (if they want) remove the moisture pad from one side. But this is another alternative, and may be attractive especially for those who do not want to wake up "blind" in the middle of the night.

I'd love to have feedback on this and if you come up with other uses for it please let me know so I can share it with others here!

New product: MEGS (Micro-Environment Glasses)

The long-awaited MEGs are here! To see more pictures, get detailed information or purchase them, please visit the Seefit website.

The makers were kind enough to send me two pairs to try out. I've spent a fair amount of time wearing them and want to share my experience thus far.

Basic description: MEGs are the first commercial moisture chamber eyewear that can take high prescriptions. They are basically a simple pair of rimless glasses with a flexible, rubbery shield built all around them. You can purchase them with a "plano" (no prescription) lens or a "demo" lens to be replaced with prescription lenses that your local optician can put in them. (Please note that if you have a high prescription you may need to shop around for the right optician.)

Frame fit: I have a ladies small and medium. They both fit me fine and I could wear both all day without any discomfort. I tried the small pair on my daughter (6yo). They're too big on her :-) but they sure look cute.

Aesthetics: They are not as discreet as a really well done custom moisture chamber, but for indoor use they're far more 'aesthetically pleasing' than wearing foam-lined sunglasses or motorcycle goggles. Personally, I would not hesitate to wear these in an office environment if I needed to. Will others notice? Yes, but crucially, they are not distracting and unlike almost all alternatives they won't interfere in any way with eye contact.

Shield/Seal fit: Within the constraints of this type of product, I think they really did quite a good job.

Now, about those constraints. First, this is not a foam-lined product. The closest equivalent to this product would be the custom-cut Eagle Vision moisture chamber or custom chambers some optometrists are able to make. In a non-custom product like this where it has to fit all kinds of people, of course the shield can't go right to your skin, but it gets pretty close, at least for me, on the top and sides. Second, how close to the skin the shield can get is limited by the need to keep an effective vent to prevent fogging, which is a problem for any kind of moisture chamber. On me, and my sister who tried them for me (for reference, I have a round face and she has a much more slender oval face) there is a large gap at the bottom of the MEGs. It's my guess that this their way of minimizing fogging. All things considered if I'm going to have a gap, the bottom is where I'd want it.

What this means is that while it will provide good protection for a great many people, it will not be adequate for some people. Here's how I look at it: If you currently literally cannot get through the day without Panoptx style completely sealed glasses or custom moisture chambers, MEGs will probably not be an alternative for you. But that leaves a lot of people whom it WILL probably help a great deal. Here are some of the best uses for them I can think of:

1) People who WOULD be wearing moisture chambers if they could only get them with their glasses prescription.

2) People who WOULD be wearing moisture chambers at work if only they weren't so bulky or distracting and didn't interfere with eye contact.

3) People who CURRENTLY wear moisture chambers as much of the time as they can but leave them off specifically for aesthetic reasons in some circumstances.

4) People who have dry eye symptoms that are inadequately addressed with their current treatments, experience a lot of discomfort, and have never considered moisture chambers because... well... they can't face the idea of wearing goggles, or they don't think they're badly enough off for moisture chambers, etc.

Now that's just addressing the sorts of people we have most often on DryEyeTalk. Then of course there's a far larger audience that I think would benefit from these - namely, just about anybody working at a computer, especially the ones that are still wearing contact lenses.

Shield/seal efficacy: Sigh. On this, the single most important question, I can't give any useful feedback except to the extent it can be inferred from the seal fit description. I wear scleral lenses during the day, which keep me so comfortable that I wouldn't notice the difference of a moisture chamber indoors. I also rely on sclerals to see so I can't just leave them out for a day to give the MEGs a trial run. Sorry... Those of you who get the MEGs, I sure would appreciate it if you would post your comments on performance here and/or on DryEyeTalk.

Colors, styles, sizes: It comes in men's, ladies' medium and ladies' small. The shield is available in several colors including black, brown, grey, red, blue.

Price: $249. Yes, I know, it's steep, especially when you factor in the cost of prescription lenses, but it's not more than a pair of prescription Panoptx. Bear in mind that there are very high costs associated with developing this kind of product. In my opinion, moisture chambers are an important investment for chronic dry eye patients, and while I can't tell you which will be best for you, this one definitely deserves consideration.

p.s. No, that's not me in the picture... I stole the pic from the seefit.net website.

Drug news: Argentis update

Meanwhile, Argentis is trucking right along with its hormonal treatments, hoping to get their Phase II clinical trial complete next year. (Don't get too excited yet... target market entry date is 2013. But some of you might be interested in participating in their Phase III trials when those get going, and that's probably just a year and a half off.

Momentum revs up for arGentis
Pharmaceutical firm in fast lane for clinical trials

arGentis Pharmaceuticals LLC is gaining momentum to get its first two therapies to the marketplace with a $10 million-$12 million capital campaign, new paths for clinical trials and a renowned business accelerator firm to help it find a drug development partner.

The Memphis pharmaceutical company is now negotiating with a clinical research organization to begin a Phase II trial of its dry eye therapy. That trial would take six weeks and company officials are hoping to conclude it in 2009. It would be followed by a lengthier Phase III trial. The therapy is projected to hit the market in 2013.

Drug news: Alcon's latest

Finally!!! It's about time we saw some Alcon dollars in the dry eye drug research world.

First, we've got cilomilast, which I've never even heard of in this context. Alcon are licensing it from GlaxoSmithKline for ophthalmic indications.

Then, we've got a closer relationship with Origenis:

Alcon expanded its existing drug research alliance with Origenis with a focus on the discovery and development of the small molecules that might one day have a role in the treatment of eye diseases.

Here's the whole article if you're interested:

Alcon Pads Eye-Disease Pipeline through Deals with GSK and Origenis

Newsblurb: Dry eyes in Ireland

First we had a big wave of dry eye publicity in the US where it seemed every slow news day had some sort of minimally educational article about dry eye and how to treat it, or at least how to line the pockets of a pharmaceutical company. Now we're seeing articles now and then in Europe and Asia on a regular basis. Here's one example:

Treat your eyes - take a screen break

eatment in eye clinics as a result of working on computers for long stretches.

Researchers at the University of Ulster showed one of the most common complaints is dry eye, which can affect large numbers of people but particularly those who work at computers indoors, in air-conditioned environments.

Johnny Moore, consultant ophthalmic surgeon, advises people to pay attention to the positioning of the computer and also to check out the humidity within the workplace or office.

"It is important that the user's seat and PC screen are adjusted to the correct height," he says. Other points to note include:

- Make the screen a bit duller as it makes it easier to read.

- People blink at least half as much as they normally do when looking at computer screen. The advice is to remember to blink and every now and then close your eyes for a few seconds.

- Every 10 minutes fix on an object 10 feet away for 10 seconds.

- Instead of reading long reams of text on the computer it may be better to print it off rather than having to concentrate for a long time on the screen.

- When you're working at your computer screen, stop every hour and take a two-minute break.

During this time, lie back in your chair and close your eyes. This will help to moisten and re-lubricate your eyes so they feel less dry and irritated.

Other advice is keep well hydrated in the modern, air-conditioned environment.

Researchers at the University of Ulster are currently undertaking a phase three clinical trial for a new drug for dry-eye treatment. Ulster is one of 30 centres across Europe involved in the research.

I wonder if Dr. Moore has any suggestions when his patients confirm that the humidity in their office has dropped into single digits....

Abstract: Vitamin A vs. Restasis for dry eye

...And it's a tie!

Really!

Both Vitamin A and Restasis appear to have improved everything EXCEPT symptoms. (Oops, I take that back, sounds like staining didn't improve either.)

Am J Ophthalmol. 2008 Oct 8.
A Comparison of Vitamin A and Cyclosporine A 0.05% Eye Drops for Treatment of Dry Eye Syndrome.
Kim EC, Choi JS, Joo CK.

PURPOSE: To compare the efficacy of vitamin A (retinyl palmitate) and cyclosporine A 0.05% eye drops in treating patients with dry eye disease. DESIGN: Prospective, randomized, controlled, parallel group study. METHODS: A total of 150 patients with defined dry eye disease participated (50 in each treatment group). In three identical clinical trials, patients were treated twice daily with cyclosporine A 0.05%, four times daily with retinyl palmitate 0.05%, or with no eye drops. Adjunctive treatment with preservative-free artificial tears was undertaken four times daily in all groups. Corneal fluorescein staining results, Schirmer tear test (without anesthesia) results, tear film break-up time (BUT), dry eye symptom score, and impression cytologic analysis results were obtained before treatment and at the first, second, and third months after initiation of treatment. RESULTS: Both vitamin A eye drops and topical cyclosporine A 0.05% treatments led to significant improvement in blurred vision, tear film BUT, Schirmer I score results, and impression cytologic findings in patients with dry eye syndrome (P < .05). CONCLUSIONS: Both vitamin A eye drops and topical cyclosporine A 0.05% treatments are effective for the treatment of dry eye disorder.

Abstract: Improving corneal topography on a dry eye

This study discusses a method for improving corneal topography accuracy when the tear film is too unstable to get a reliable result otherwise. This sounds like something that would be particularly useful for refractive surgery patients who have ablation irregularities and dry eye. The authors also mention this technique may later be useful in examining the tear film itself.

Estimating corneal surface topography in videokeratoscopy in the presence of strong signal interference
IEEE Trans Biomed Eng. 2008 Oct;55(10):2381-7. Links.
Alonso-Caneiro D, Iskander DR, Collins MJ.

Videokeratoscopy techniques rely on a number of factors in order to achieve accurate estimates of corneal surface topography. Good tear film quality, minimal reflections from eyelashes, and minimal eye movements are essential for corneal topography estimates to be reliable. However, in practice, these ideal conditions may not always be fulfilled, especially in cases of subjects diagnosed with dry eye syndrome, having narrow palpebral apertures, long eyelashes, or nystagmus (uncontrolled eye movements). Such nonoptimal conditions of image acquisition result in poorer estimates of corneal topography. The aim of this paper was to devise a technique that would provide more accurate estimation of corneal topography in such situations and particularly when the source of signal interference is strong. This was achieved by developing a set of algorithms that extract the interference from the acquired raw videokeratoscopic image and filter the topography according to the interference location. The experiments carried out with test surfaces and real corneas showed that this new technique leads to a significant improvement in the topography estimator. Additionally, it is an interference indication procedure that, in the future, could be used for the purpose of tear film quality estimation.

Abstract: Dry eye and cataract surgery

Good points... enough that I'll forgive the poor translation even.

[Not to ignore the dry eye of cataract patients after surgery]
Zhonghua Yan Ke Za Zhi. 2008 Apr;44(4):291-2.

Sun XG, Shi YY, Zhang C.

Dry eye syndrome following cataract surgery was concerned about recently. Two kinds of dry eye were clinically observed after cataract surgery, early dry eye and chronic dry eye. Most cases of early dry eye, who usually had the normal lacrimal secretion before surgery, were reversible and involved in some of factors associated with surgery and post-surgery medication. But most cases of chronic dry eye, who have abnormal lacrimal secretion or "borderline state" of lacrimal secretion test before surgery, may suffer from the ocular surface diseases related to irreversible dry eye disease. It is significantly important for maintaining of the ocular surface stability and recovery of vision acuity after cataract surgery to do early diagnose and promptly manage the dry eye syndrome.

Abstract: More on contact lenses

Companion study to the previous, examining more signs in contact lens wear.

Mucins and ocular signs in symptomatic and asymptomatic contact lens wear.
Optom Vis Sci. 2008 Oct;85(10):E930-8.

Berry M, Pult H, Purslow C, Murphy PJ.
University of Bristol, Academic Unit of Ophthalmology, Bristol, United Kingdom. mon.berry@bristol.ac.uk

PURPOSE: Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds (LIPCOF) are related to dry eye symptoms in contact lens wearers. Both clinical signs are assumed to be related to mechanical forces during blinking. As the mucus layer is a protector of the ocular surface tissue, this study investigates whether any alterations of mucins are detectable comparing symptomatic and asymptomatic soft contact lens wearers.

METHODS: Comfort was evaluated using the Contact Lens Dry Eye Questionnaire. Corneal staining, LWE, and LIPCOF were assessed in the right eyes of 50 (19 men, 31 women; mean age, 32.1 +/- 11.4 years) experienced lens wearers. The tear film was sampled using Schirmer strips pressed onto the temporal conjunctiva and from harvested contact lenses. Mucins were assessed in dot-blots and Western blots after electrophoresis on 1% agarose or 4 to 12% NuPAGE Gels. Non-parametric analyses were used to study differences between groups and correlations between objective tests, mucins, and symptoms.

RESULTS: Thirty-one subjects were classified asymptomatic and 19 symptomatic by the questionnaire. LWE and LIPCOF were significantly increased in the symptomatic group (p < 0.035). MUC5AC reactivity was significantly decreased in symptomatics (p = 0.050). MUC4 was correlated to temporal LIPCOF and LWE, (r = -0.47 and -0.46; p < 0.01). MUC16 and MUC5AC correlated with corneal staining (0.36 < r < 0.53; p < 0.04).

CONCLUSIONS: Symptomatic contact lens wearers exhibit significantly more LWE and LIPCOF, and decreased MUC5AC reactivity. LWE and LIPCOF are significantly correlated; this may reflect their common frictional origin. Increased friction might follow from insufficient mucins, or an altered composition of the resident mucins at the ocular surface. In this study, we show that decreased mucin production is associated with the severity of LWE and LIPCOF.

Abstract: Clinical tests for successful contact lens wear

Rather an interesting one on attempts to quantify what makes for comfortable contact lens wear.

Clinical tests for successful contact lens wear: relationship and predictive potential.
Optom Vis Sci. 2008 Oct;85(10):E924-9.
Pult H, Purslow C, Berry M, Murphy PJ.

PURPOSE: Although comfort is important for contact lens wearers, common clinical tests can fail to predict patients' symptoms. Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds (LIPCOF) are related to dry eye symptoms in lens wearers. This study investigates the predictive value of LWE and LIPCOF as objective measures of discomfort, and their relation to the ocular surface in soft contact lens wearers.

METHODS: Subjects were classified as symptomatic or asymptomatic, using the Contact Lens Dry Eye Questionnaire (CLDEQ). Pre-lens tear break-up time (PLBUT), limbal and bulbar hyperaemia, corneal staining, LWE and LIPCOF were assessed in the right eyes of 61 (23 M, 38 F; mean age 32.1 years; range = 18 to 55) experienced contact lens wearers. Differences between groups, and relationships between LWE, LIPCOF (nasal, temporal and sum) and objective signs were examined using non-parametric analyses. The positive and negative predictive values for symptoms of each objective measure were calculated.

RESULTS: Thirty eight subjects were classified as asymptomatic, 23 symptomatic. LWE and LIPCOF severity scores were significantly increased in symptomatic patients (U-test, p < 0.03), while no significant differences were found between groups for PLBUT, corneal staining or hyperaemia (0.29 < p < 0.88). Significant positive correlations were found between LWE and LIPCOF scores (temporal r = 0.67, p < 0.001; nasal r = 0.39, p < 0.001), and between LWE and hyperaemia (bulbar, r = 0.28, p < 0.001; limbal r = 0.36, p < 0.001). Age and gender were different in the two groups (p < 0.05). The predictive value of temporal LIPCOF was positive = 56.9%, negative = 77.1% with a cutoff value of > or =2 (PPV/NPV/cutoff value), of nasal LIPCOF 70.7%/75.0%/> or =1, of LIPCOF Sum 79.8%/86.5%/> or =2, and of LWE 53.1%/81.1%/> or =1.

CONCLUSIONS: Contact lens wearers with dryness symptoms exhibit significantly more LWE and LIPCOF, but not increased corneal staining, bulbar hyperaemia or decreased PLBUT. LWE and LIPCOF are significantly correlated: this may reflect their common frictional origin. LIPCOF Sum severity scores appear to be most predictive for symptoms.

Abstract: Auto-immune dry eye

Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sjögren's syndrome) and its possible contribution to the development of ocular surface oxidative injuries.
Histol Histopathol. 2008 Dec;23(12):1477-83.
Cejková J, Ardan T, Simonová Z, Cejka C, Malec J, Dotrelová D, Brunová B.

Previous studies have described elevated lipid peroxidase, myeloperoxidase and xanthine oxidoreductase/xanthine oxidase levels on the ocular surface of patients suffering from autoimmune dry eye (Sjögren's syndrome, SS). Reactive oxygen species generated by various enzymatic systems may be dangerous to the eye if they are not sufficiently cleaved by antioxidants. Because antioxidants have not been investigated in dry eye, the aim of this study was to examine the expression of antioxidant enzymes that cleave reactive oxygen species and play a key role in antioxidant protection. Conjunctival epithelial cells of dry eye (SS) patients were obtained by the method of impression cytology using Millicell membranes. Normal eyes served as controls. In the conjunctival epithelium superoxide dismutase, catalase and glutathione peroxidase were examined immunohistochemically. The enzyme expression levels were determined by image analysis and statistical evaluation. In contrast to normal eyes, where antioxidant enzymes were highly expressed in the conjunctival epithelium, in dry eye their expression was much less pronounced in correlation with the increasing severity of dry eye symptoms. Our study suggests that the decreased expression of antioxidant enzymes in dry eye disease (SS) contributes to the development of anterior eye surface oxidative injuries.

Abstract: The Aging Lacrimal Gland

The Aging Lacrimal Gland: Changes in Structure and Function.
Ocul Surf. 2008 Oct;6(4):162-174.
Rocha EM, Alves M, Rios JD, Dartt DA.

ABSTRACT The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

Abstract: Epithelial-immune cell interaction in dry eye

Should be an interesting read for the docs that can access the full article....

Epithelial-immune cell interaction in dry eye.
Cornea. 2008 Sep;27 Suppl 1:S9-11.
Pflugfelder SC, de Paiva CS, Li DQ, Stern ME.

Dry eye is a potent stimulus of both innate and adaptive immune systems. At the nexus of the dry eye inflammatory/immune response is the dynamic interplay between the ocular surface epithelia and the bone marrow-derived immune cells. On the one hand, ocular surface epithelial cells play a key initiating role in this inflammatory reaction. On the other hand, they are targets of cytokines produced by activated T cells that are recruited to the ocular surface in response to dry eye. This interaction between epithelial and immune cells in dry eye will be thoroughly reviewed.