advances in understanding of dry eye disease during the last decade

[wetEyes]

The following text summarises how much the understanding of dry eye disease has increased during the last decade (from Gayton, J.L.: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720680/):

"The last decade brought about a significant improvement in the understanding of the etiology and pathogenesis of DED.

One major advance in the understanding of DED is the recognition of the two distinct components of the disease–tear evaporation and insufficient tear production–and their roles individually or concomitantly in DED.19

Another improvement is the identification of tear film instability as a common feature of the various stages of DED and the realization that the thickness of the lipid layer might determine the stability of the tear film.20

Additionally, appreciation of the role of inflammation in DED was one of the most important factors that aided in the understanding and treatment of DED.

The findings of the association of inflammation with reduced tear secretion and subsequent damage to the ocular surface led to the proposal of a unified concept of DED."

As you can see, it has been a quantum leap.

I think while the last decade brought only moderate advances in treatment (mainly: cyclosporine, omega 3, better artificial tears), the understanding that has been grown during the last 10 years will help to revolutionise treatment in this decade - hopefully in the next few years.

I am especially hopeful about:
a) Novagali's Cyclokat because my dry eye doc helped in the phase III trials and said it is much more effective than Restasis. Results for phase III are overdue.

b) Resolvyx' RX-10045 because their preparation is some kind of omega 3 extract. And if Omega 3 is effective even at the systemic level, it must be much more effective locally. Also, the phase II results have been promising.

c) Artificial tears that remain longer on the ocular surface. Imagine a drop that completely relieves your dryness for 30 minutes. Maybe tears enriched with nano particles will do the trick. But I'm just guessing.

d) Increased insight on the relationship between diet and dry eyes. For example, I would like to see a large, well-conducted study on antioxidants.
I very much doubt that omega 3's are the only aspect of nutrition that significantly affects the glands and the tear film.

Let me know what you think.

[Michael2]

very interesting. good news

having first hand experienced the difference that a little meibum can make on the ocular surface, let me say that the whole concept of this disease is absurd. for example, the difference between your glands being 40% and 50% blocked makes such a significant difference in pain, how 'full' your eyes feel, etc.

of course, signs aren't a huge factor, and its good that there's a paradigm shift in how docs are addressing the disease. i still think stem cells are the most promising idea

[indrep]

weteyes you might google DEWS Report 2007. Its a long a read and addresses some of the things you already found.

[dave25]

Great post! Thanks for the info.

[wetEyes]

@ Micheal2

How do you think could stem cells help with dry eyes? I know they are already used for severe cases with limbal cell deficiencey, but not for the average patient.

@ Indrep

Thanks for the suggestion. I have already read large parts of the report. This spring the Tear Film & Ocular Surface Society will publish a report specifically for Meibomian Gland Dysfunction. That will be interesting to read.

[Michael2]

read this article, it's about the 'differentiation of the sebaceous gland.' I think, if we could find a way to control the differentiation of stem cells into healthy sebaceous glands, we could rescue the severely inflamed or atrophied meibomian glands. in essence, i think this would cure MGD

http://www.ncbi.nlm.nih.gov/pmc/arti...e0102_0064.pdf

[Lucy]

Hi WetEyes:

As you can see, it has been a quantum leap.

As one who has suffered from the dreaded dry eye syndrome, that statement just isn't the case. I did not read the information you posted because it's hard for me to read articles of any length or technical terms etc.

The only thing I can speak of that is "new" and it certainly isn't a quantum leap is Restatis. I believe Restatis helps between 1/3 to 1/2 the patients who use it. I've tried it twice, once for 6 weeks and another for 7 months and it did not help, unfortunately.

They have been talking about stem cells for the past 10 years and likely before that, but I just had no reason to pay attention until I met up with a Lasik surgeon one cold, snowy day in January 2000.

Much of the stuff written is fluff and "studies" that never amount to much except $$ for the pharma companies. I read your profile and know you are highly educated. Don't believe what you read from drug studies etc. Believe it when you have it in your EYE and it feels good. Lucy

[wetEyes]

Hey Lucy,
I know it's frustrating that the treatment options for dry eye are still insufficient for many sufferers. I personally get eye pain for hours every time I expose my eyes to cold wind in the morning when my tear film is at its worst. But I know your eyes are much worse.

And trust me, I am very critical of studies where I smell that some people have a financial interest in. I have studied business & management and am still often surprised and disappointed how money corrupts many people and makes them act in ways that are detrimental to other people.

As to stem cells, I still don't belief that they will affect dry eye treatment much in the next 10 years.

But I do think that the understanding of the disease has advanced very much during the last years and that it will result in vastly improved treatment within the next few years.

Unfortunataly, dry eye due to Sjögren's Syndrome is especially severe and hard to treat

[Keymaker]

Has anyone kept up with LUX BIOSCIENCES and the 2 items they are working on? I know they are in early stages but I was impressed.

[wetEyes]

Why don't you go to their website? There you should find all the information that is relevant.

Also, I would only put my hopes in treatments that have at least successfully completed phase II.

[Keymaker]

I have read the material on their website. Since you appear to be up on the subject I wanted to get your thoughts. By the way, all the ones that you mentioned started out as clinical ideas before they got to stage 2.

[wetEyes]

Of course you're right. Every potential treatment starts as just an idea. What I was trying to say was that most candidates from phase I never make it to phase III or even the market.

I just looked at their website and here is my impression:

positive:
* their uveitis drug seems to be getting FDA approval which means they get revenue from it, making them less likely to go bankrupt while they are developing their dry eye therapies
* also they have received $50 million from investors half a year ago - also making it less likely that they go bankrupt soon

negative:
* there is no information on when they plan to start phase II of their dry eye drug LX114

[indrep]

As quoted from Eye World Week 8

Ocular surface disease is prevalent among Americans, but there is only one drug—Restasis (cyclosporine, Allergan, Irvine, Calif.)—approved by the Food and Drug Administration (FDA) for treating it. And, as Michael A. Lemp, M.D., clinical professor, Georgetown and George Washington Universities, Washington, D.C., points out, “even [cyclosporine] was not approved on the basis of a primary efficacy endpoint, rather a post-hoc analysis of a secondary endpoint. So the FDA approved it on the basis of something they said they would not approve before.”

The FDA traditionally requires the drug sponsor to demonstrate a statistically significant improvement in both an objective sign of the disease and a symptom. However, Dr. Lemp said investigators now have been printing reports that the signs and symptoms do not go together. Typically, patients get symptoms before they get any of the signs used in clinical trials, so patients are symptomatic, but when the physician looks at the patient and stains the eyes or measures tear production, they are not finding any signs of the disease. “We are just beginning to get all of this documented in peer review literature, so I am not trying to be too critical of the Agency because they can only act on what is already published in the peer-reviewed literature in terms of what they should be using for endpoints in clinical trials,” Dr. Lemp said.

There are over 20 drugs in the pipeline for treatment of dry eye disease. The FDA has made it very clear that another drug like Restasis(only working on 15% of patients) will not get approved. Especially in the same manner. The ophthalmic industry is trying to come to some consensus on what determines progress in the treatments. At the ARVO meeting last Spring and in considerable nonbiased publications osmolarity is becoming the standard for improvement and diagnosis of dry eyes. It could easily be another 2-3 years before a "standard of care" is agreed upon and the FDA begins to approve drugs. Unfortunately, of these drugs in the pipeline, that I am familiar with, they only address one issue or symptom of the disease.

What's right with this is, addressing one issue is better than nothing and we are a lot closer now than 10 years ago.

[Guest]

What I was trying to say was that most candidates from phase I never make it to phase III or even the market.

You are so right about this.

Because of that, I can't be bothered to read about any new drugs until they are at the very least in phase 3 trials. I just hate getting my hopes up for stuff that doesn't make it to market.

But then again, maybe if I end up exhausting all currently available treatments I'll start reading some of that stuff... maybe at that point the disapointment in a drug not making it to market will be outweighed by the hope one gets from reading about the potential of these new products.

I'll be getting my blood drawn for autologous serum drops on Monday... bleh... I hope it helps me...

[irish eyes]

Hi Saag

I hope the serum drops help. I was accepted for trials (for one year) and have been using them around 6 months now.

They have certainly helped me; I still have irritating symptoms but compared to how bad my eyes were - !!

My consultant says there has been a marked improvement in the ocular surface so that is good news.

This was a last resort therapy for me as all conventional stuff had proved useless.

So not 100% but it depends on your starting point when assessing success,