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Iluvien Treats Diabetic Macular Edema for 3 Years

US ILUVIEN LOGOIluvien is now available in the United States!  Finally receiving FDA approval in late 2014, the injectable sustained release intravitreal implant  is on the market.

Alimera Sciences states that Iluvien (sustained release of fluocinolone) will release its drug for up to 3 years.

Iluvien Treats Diabetic Macular Edema

Diabetic macular edema is the most common vision threatening complication of diabetic retinopathy.  In essence, normal blood vessels of the retina become leaky due to the diabetic retinopathy.

Fluid accumulation in or near the center of the macula is called diabetic macular edema (DME).  This is also known as clinically significant macular edema (CSME) if you are a doctor.

DME often causes blurry vision and in extreme cases can cause legal blindness.

Therapy is aimed at stopping the leakage.  With time, the macular edema may “dry up.”

Treatment options include laser, anti-VEGF (e.g. Avastin, Lucentis, Eylea), intravitreal steroids (Kenalog) or sustained release intravitreal implants (Ozurdex, Iluvien).Size comparison of Iluvien to Pencil Tip | Randall Wong, M.D., Retina Specialist, Fairfax, Virginia

Iluvien is Injected Painlessly

Iluvien is injected directly into the vitreous.  The sustained release system will release fluocinolone for 3 years.  The actual “pellet” is small enough to fit inside a 25 gauge needle.  It is smaller and thinner than a grain of rice.  You may click on the image to enlarge.

By injecting directly into the eye, as with all intravitreal injections, only small amounts of drug are needed to treat the retina.

The steroid will chemically stop the retinal vessels, affected by the diabetic retinopathy, from leaking.

36 month Delivery

While intravitreal drug delivery is not novel, the duration of the product is unique.

Constant treatment for 36 months may have huge practical advantages; namely fewer offices visits and less testing.

The economics of this are intriguing.  The practical consequences are even more staggering.  In short, this could mean far fewer trips to the retina specialist for the patient AND the family.  Fewer office visits translates into fewer examinations and testing.

We’ll see.

 

 

 

 

Laser Treatment for Diabetic Macular Edema

Laser photocoagulation is still the best treatment for diabetic macular edema.  Diabetic macular edema, or DME, is the most common complication of diabetic retinopathy and it will affect almost everyone with the eye disease.

DME is also known as CSME (clinically significant macular edema).  The two terms are exactly the same for our purposes.

Before Laser Treatment

Diabetic macular edema before laser treatment.
Click to Enlarge

This is a retinal photograph of a patient with diabetic macular edema.  The white spots and flecks are evidence of chronic swelling of the retina from diabetes.  The swelling involves the macula, the most sensitive portion of the retina and causes loss of vision.

The goal of any treatment, laser, steroid injections or anti-VEGF injections is to reduce the swelling.  If the swelling improves, it is highly likely the vision improves, too.

Usually, a fluorescein angiogram is performed to demonstrate where the normal retinal blood vessels are leaking.  Using the energy of the laser, the areas of leakage are heated and this usually, but not always leads to improvement of the swelling.

Treatment can involve anywhere from a few to dozens of burns…all depending upon the number leaks.

Laser treatment to the center of the macula could lead to a permanent blind spot in the vision and, therefore, is not always the best treatment for every patient.  In these types of cases, intraocular injections of anti-VEGF or steroids might be a smarter option.

Laser Treatment Reduces Macular Edema

This is the same retina several months after laser treatment.  Note the white spots have all disappeared.

Diabetic macular edema after laser treatment.
Click to Enlarge

After 4-6 months, I can usually tell if the laser treatment is effective or needs to be augmented (ie. repeated).  At times, I’ll know I’ll need to treat with a combination of laser and intraocular injections of Avastin, steroids or even Ozurdex.

The laser treatment for diabetic macular edema is very similar to weeding a garden.  It is not a cure, and will have to be repeated.

What Does This Mean?

There are a variety of treatments for diabetic macular edema.   Laser treatment is still the standard of care for treating this common condition seen with diabetic retinopathy.

Though we have a variety of effective treatments available, we still don’t have a cure.  The best advice remains regular examination and treatment as early as indicated.

Randall V. Wong, M.D. 
Ophthalmologist, Retina Specialist
Fairfax, Virginia

Iluvien Gains Ground

Iluvien Approved in EuropeIluvien continues to make progress outside the US for treatment of macular edema due to diabetic retinopathy.

Iluvien, a sustained release drug delivery system from Alimera Sciences, is a proprietary intraocular injection for the treatment of diabetic macular edema.  Iluvien releases a steroid for up to 36 months and may be a significant treatment for the most common “complication” of diabetic retinopathy.

Normal retinal vessels tend to leak the clear fluid part of blood into the retinal tissue.  If the fluid accumulates in the macula, vision is often decreased.  Treatment is aimed at preventing further accumulation of fluid and thus preventing further loss of vision.  Often the “swelling” can be fixed and vision improves.

Presently, diabetic macular edema is treated with laser, anti-VEGF medicines or steroids.  Unfortunately, treatment for diabetic macular edema is similar to “weeding a garden”…the leakage tends to come back.

Austrian Approval

Iluvien was just approved for use in Austria several weeks ago.  This marks the first sustained release pharmaceutical in that country for the treatment of DME (diabetic macular edema).

United Kingdom Follows Suit

More recently, the United Kingdom allowed marketing authorization for Iluvien, too.  This is the second EU (European Union) country to accept the drug.

Not FDA Approved

Iluvien is not approved for use in the United States.  Most recently, the FDA was not satisfied with the safety data presented by Alimera Sciences, Inc. and recommended additional clinical trials.

What Does This Mean?

Treatment of macular edema from diabetes is difficult and can be frustrating.  Intraocular injections have been a great alternative to the gold standard of laser treatment.

Laser treatment for diabetic macular edema is not appropriate for all patients and alternative treatments are needed.

Ozurdex, a product similar to Iluvien, is FDA approved but not for diabetic macular edema yet has been used “off label.”

 

 

 

 

 

 

Laser and anti-VEGF Best Treats Diabetic Macular Edema

Laser and anti-VEGF Best Treatment for Diabetic Macular Edema

Treating diabetic retinopathy with both laser and anti-VEGF injections may be the best way to treat patients with diabetic macular edema.  Diabetic macular edema is the most common “side effect” of diabetic retinopathy and is the leading cause of vision loss in patients with diabetes.

The results of a large, multicenter, randomized clinical trial compared several permutations of laser and the anti-VEGF drug, Lucentis.  Intraocular steroids were included as well.

To date, standard treatment, or the standard of care, includes treating the retina with laser photocoagulation to retard the loss of vision.  Not all patients can be treated with this modality and intravitreal injections of anti-VEGF and also of steroids have been found to be useful treatment for those in whom laser is not applicable (myself included).

Whether or not a patient receives laser or injections, the treatment of diabetic macular edema is akin to “weeding” a garden.  The treatments are not a cure, and just like weeding a garden, the “leakage” may be controlled for a time, but only to return.

In short, diabetic macular edema recurs and requires retreatment.

The study found that injections of Lucentis/ranibizumab followed by either prompt or deferred laser for 6 months, was superior to laser treatment alone.   The study also found that this combination was superior to a similar combination treatment with intraocular steroids.

In addition, intravitreal injections of anti-VEGF and laser (immediate +/- deferred) led to the most improvement in vision, resolution of macular edema and, over a two year period, required fewer treatments!

What Does This Mean?

Diabetic macular edema is often difficult to treat.  The number of tools we have to treat the disease was quite limited until the introduction of intraocular steroids and anti-VEGF.  Over the past few years, because of these additional modalities, we have been able to help more patients than with just laser alone.

This new study not only validates the use of anti-VEGF medications, but also hints that anti-VEGF may be superior to steroids.  More studies will tell.

Most importantly, however, the study describes a treatment regimen that leads to improvement, stabilization and reduction in the number of treatments!

This means better vision and fewer office visits, right?

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Macular Edema: So Many Types

Macular edema simply means accumulation, or build-up, of fluid of the macula.  Synonyms include; clinically significant macular edema (CSME), diabetic macular edema (DME), cystoid macular edema (CME) and retinal edema.  There are slight nuances with some of the terms, but basically it means “swelling.”

Macular Edema – a generic term indicating fluid build up in the macula, but can be from any cause; diabetes, macular degeneration, vein occlusions; etc.  I prefer to use it to distinguish macular swelling from macular degeneration versus diabetic retinopathy.

Diabetic Macular Edema (DME) – this is probably the most common term that I use and is found in the literature.  This is basically the same as CSME, that is, swelling and thickening caused by diabetic retinopathy.  I think it a more useful term as it contains the word “diabetic.”  It becomes self explanatory.

Clinically Significant Macular Edema (CSME) – basically macular swelling related to diabetic retinopathy only.  More specifically, it does imply that it meets certain criteria requiring treatment.  It is a term that was created to establish when laser treatment was necessary to treat the macular edema due to diabetic retinopathy.

Cystoid Macular Edema (CME) – this is a bit more esoteric.  It refers to macular fluid, or thickening,  from really any cause, except diabetes.  CME may develop after a retinal vein occlusion, following cataract surgery or cases of uveitis.

Retinal Edema is thickening of any part of the retina.  It really means non-macular swelling.  Since this has little or no impact on the vision (as the macula is uninvolved), it isn’t used very often.  It is also too broad a term to have much use.

What Does This Mean? As I write, I try to keep the terms pretty straightforward.  I think for our purposes diabetic macular edema (DME) is best suited for situations caused by diabetic retinopathy.  Macular edema is a term best used for swelling from macular degeneration.  Fewer terms; keeping it simple.

Iluvien® For Diabetic Macular Edema Has Eyes on FDA

™Alimera Sciences’ “Iluvien®” moves closer to FDA approval for the treatment of diabetic macular edema.  Iluvien is an extended release drug delivery system designed for direct intravitreal injection to the eye.  Iluvien will release a steroid, fluocinolone acetonide, for up to 36 months to treat retinal swelling.  The company has announced pivotal results in the ongoing FAME (Fluocinolone acetonide in diabetic macular edema) study.  This is a phase 3 FDA clinical trial.

An earlier post covered Iluvien’s safety and efficacy in phase 2 trials for the treatment of diabetic macular edema.

Diabetic Macular Edema is the most common complication of diabetic retinopathy.  The traditional laser for diabetic retinopathy has been usual treatment for about 30 years.  I have written previously about the emergence of new treatments and new technologies to treat the diabetic macular edema.  Intravitreal steroid injections, anti-VEGF and sustained release intraocular drug delivery systems are all the rage.

FDA Clinical Trials dictate how medicines are approved for treatment of disease in the U.S.  I have always cautioned that you must consider a “treatment” only if it has already been FDA approved.  Most of what is advertised as treatment is neither FDA approved nor even studied.

There are 4 different steps to passing the FDA requirements. There are 3 phases of clinical trials (sometimes an additional phase 4 is required) and the NDA (New Drug Application).

The phase 3 clinical trial (FAME) is almost complete.  The study will proceed to 36 months.  The early phase 3 findings indicate improvement in vision in about 25-30% of patients after the first 24 months of the study.

What Does This Mean? This is huge.  It means that there is merit to what the company anticipates.  Technically, phase III trials determine if the drug is useful and confirms safety.

New Drug Application (NDA) is usually the last step for a company, or sponsor, to be allowed to market and sell the drug.  Alimera expects NDA submission later in 2010 after completion and analysis of the phase 3 data.

Alimera’s Iluvien is close to reality for the treatment of diabetic macular edema.

For fun, compare the status of this drug, Iluvien, to E10030.  I wrote about Ophthotech’s E10030 a few days ago.  E10030 is an anti-PDGF aptamer that treats wet macular degeneration.  This drug is about to enter phase 2.

“Randy”

Randall V. Wong, M.D.
Ophthalmologist, Retina Specialist
Fairfax Virginia

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Steroids Likely to Help Diabetes

Ok, maybe a bit dramatic, but another article was recently published stating that intravitreal injections were used with success to treat diabetic macular edema.   These effects lasted at least 5 years, the duration of the study.

This was a small study where two groups were compared.  One group received intravitreal injections of triamcinalone (a steroid) for the treatment of diabetic macular edema.  The second group received a placebo.

After two years, the second group then started receiving the steroid.  The first group continued.  Occasionally, laser was used in either group.

The results were that vision improved and swelling decreased in the first group.  In the second group, the vision improved and swelling decreased, but only after receiving the steroids.

What Does This Mean? The other day, I reviewed a small study (Eye Injections Challenge Eye Laser for Diabetic Retinopathy) and had a few criticisms.  This study, too, has the same pitfalls.  Don’t take away that all small studies are worthless, they are not.

A few months ago, there was some discussion regarding a couple of emerging new drug delivery systems available for ophthalmic use.  Iluvien® (Alimera) is an injectable sustained release system that will release steroid (fluocinalone) for the treatment of diabetic macular edema.  Clinical trials are underway.

Ozurdex™ (Allergan) is the first sustained drug delivery system to hit the market.  It was approved last June 2009 by the FDA for treatment of macular edema caused by retinal vein occlusions.  Though not approved directly for the treatment of macular edema found in diabetic retinopathy, my prediction is that it will be used “off-label” in the near future.

I think, slowly, we are moving to the point where intravitreal injections are going to replace laser therapy for the treatment of diabetic macular edema.  I am using the term “injections” rather loosely as I also am including the use of sustained release systems.  These, too, will be delivered by an injection method, similar to intraocular injections.  The only difference is that the sustained release systems will deliver the pharmaceutical over a much longer period, thus, requiring fewer “treatments.”

The full article is referenced here;  Ophthalmology. 2009;116(11):2182-2187.  There is no link as viewing may require a subscription.

“Randy”

Randall V. Wong, M.D.

Ophthalmologist, Retina Specialist
Fairfax, Virginia

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Eye Injections Challenge Eye Laser for Diabetic Retinopathy

There is a small study just published in the journal “Ophthalmology” stating that intraocular injections of Lucentis® were superior to laser photocoagulation for the treatment of diabetic macular edema.  As you read this, don’t forget that the “gold-standard” for treatment of diabetic macular edema is still laser photocoagulation.  These “studies” are very small and not of the caliber needed to change the way we practice, but there is still some merit to the findings.

In this study, 126 patients with diabetic macular edema were split into 3 groups;

  1. treated with Lucentis® only
  2. treated with laser only
  3. treated with laser, then Lucentis

Of the 3 groups, the patients receiving Lucentis®, when compared to the laser only group, had the most improved vision and reduced “thickness” or “swelling” of the macula.  The 3rd group, where laser and Lucentis® were combined, was not significantly better in terms of vision, but the swelling was improved more than laser only.

What Does This Mean? The study indicates that intraocular injections of anti-VEGF therapy are better than laser treatment for diabetic macular edema.  If you watch the internet, many “authorities” will start proclaiming that this is a new, and better, treatment for diabetic macular edema.  But we should be cautious.

First, the best studies require that the “studies” are prospective, randomized and double-blinded.  These studies are prospective (vs. retrospective), randomized to treatments options, and basically, no one knows what treatment is administered, including the doctors and patients.  This helps remove bias and placebo effects.  This also means, in a study like this, “fake” lasers would have been performed along with “sham” injections.  After the study, a code would be cracked to disclose which treatments were given to which patients.

Second, the study is too small and too short to have allow any significant meaning.  “Statistical significance” means that an adequate number of patients were studied such that the results could not have occurred by chance.  I don’t know the actual number of patients needed, but most likely would have involved hundreds instead of tens and would have involved more than one testing center.

We also don’t know if the effects are long-lasting.  We only know there was improvement  in the short period of the study.  Now if the effects are still noted 1-2 years after treatment, for example, then maybe we are on to something.

Last, many aspects of the patient selection and treatment are not standardized.  For example, we don’t know if the patient selection was biased in any way that might favor one treatment over another.  For example, perhaps everyone in one group had better sugar control than the other.

My point is, that studies such as this are suspect due to many shortcomings.  Proper prospective, randomized, double-blinded studies take years to develop, perform and analyze.  The AREDS1 Study is an example.  These studies also take large reserves of cash.

The value of these studies is; however, that if similar “small” studies have similar themes, then these may serve as a nidus to create and form much larger, more formidable studies.  Also, for the clinicians (aka yours truly), it also gives us information about alternative treatments that seem viable.

“Randy”

Randall V. Wong, M.D.
Ophthalmologist, Retina Specialist
Fairfax, Virginia

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Intraocular Drug System Passing FDA Testing

Earlier this week, I wrote about a device, Iluvien ™, that will release steroid into the eye.  This drug delivery system is manufactured by Alimera Sciences.

Read my earlier post “Company Hopes Injectable Implant To Cure Diabetic Macular Edema.”

Alimera Sciences has announced that early data is showing that the drug system is safe and effective in humans.  The results are preliminary, but promising.

Phase 2 clinical drug trials are designed to show safety of a drug at different doses.  So far, after 18 of 36 months have been completed, both high and low doses of Iluvien™ appear to be safe and free from systemic side effects.

If you recall, Iluvien ™ releases fluocinalone, a steroid for the treatment of diabetic retinopathy.  It is also exciting to find that both doses of Iluvien ™ may be effective at reducing macular edema and improving vision.

In short, the FDA (U.S. Food and Drug Administration) testing seems to be going as planned for the Alimera Sciences.  The Iluvien drug delivery system moves another step closer to approval (after phase 2, a phase 3 clinical trial will need to be competed).

Have a great weekend.

“Randy”

Randall V. Wong, M.D.
www.TotalRetina, com
Ophthalmologist, Retina Specialist

Company Hopes Injectable Implant Cures Diabetic Macular Edema

Alimera Sciences hopes that its Iluvien ™ insert will be effective against diabetic macular edema.  Iluvien™ will release a steroid called fluocinalone acetonide (FA) after insertion into the eye.  The Iluvien™ system will deliver the steroid for up to 3 years.  It is anticipated that intraocular steroid release may control macular edema and improve vision.  The company has a study underway to determine just how effective this intraocular, sustained release drug system for the treatment of diabetic macular edema can be.

Alimera Sciences’ web site.

Is this new? Well, yes and no.  The technology is new.  A small implant will be injected into the eye.  The device will release a small amount of steroid into the vitreous for up to 36 months.  The injection site will be very small and will not require any stitches to close.  The entry point will be so small that it will self-seal.

“Old Drug – New Tricks” The drug, fluocinolone acetonide (FA), is not new.  It is an old, well studied, steroid.  Topical steroid drops, oral steroids and even intravenous steroids (IV) do not get into the eye very easily.  In order to get enough drug into the eye via these methods, the doses required become quite high, thereby increasing the likelihood of systemic toxicity.  Ideally, the direct insertion of the drug to its target tissue (the retina) will be more effective in treating macular swelling due to diabetic retinpathy (aka diabetic macular edema) than present treatments.  To state another way, by simply changing the route by which a drug is delivered (in this case directly into the eye versus, say, eye drops), the drug becomes more effective.

This is not really new news. If you have been reading carefully over the past year, steroids have been very useful for the treatment of macular swelling, not only in patients with diabetes, but also in cases of macular degeneration, retinal vein occlusions, etc.  Intraocular injections of steroids, such as triamcinalone acetonide (TA), have been widely used by retinal surgeons for the past 5 – 10 years, but they often need to be repeated.  A sustained release delivery system is needed (give an injection once, and it lasts for years).  So, using steroids to treat retinal swelling just makes sense.

Ozurdex® received FDA approval in June 2009. Allergan, Inc., just released its new steroid releasing implant.  Ozurdex® is an injectable sustained release system that was FDA approved in June of this year.  It is now available for patient use.  Ozurdex® also releases steroid inside the eye for up to 6 months.  The system then safely dissolves.  This system was FDA approved for the treatment of retinal swelling (aka macular edema) caused by retinal vein occlusions.  I predict that it will soon be used, off-label, for the treatment of diabetic macular edema.  Read my previous post regarding Ozurdex®.

This is all good news. To date, the Ozurdex® and Iluvien™ implants both validate the effectiveness of intraocular steroids for the treatment of diabetic macular edema.  Both are intravitreal, long term release systems.  They are small and can be delivered safely in an office.  It is exciting that new treatments, using well-studied medicines, are now available for treating such a prevalent complication of diabetic retinopathy.

Lastly, the advantages of sustained released systems can not be understated.  While it may sound a little aggressive to be injecting medicine directly into the eye, it is proving to be very effective in treating many eye diseases such as macular degeneration.

Intraocular injections have two major advantages, it delivers drug right where you want it and it takes lower doses than otherwise would be needed if given orally or by intravenous.  Therefore, little chance of side effects to the rest of the body!  The drug works at lower levels because it is injected right where it is needed.  It also may reduce the number of office visits (i.e. costs) and also increases “compliance,” that is, there is no question the patient is taking his/her “medicine.”

“Randy”

Randall V. Wong, M.D.
www.TotalRetina.com
Ophthalmologist, Retina Specialist

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Currently, I see patients with retinal diseases; macular degeneration, retinal detachment, macular holes, macular pucker within several different practices.....it's a different arrangement, but it allows more continuous care with many eye specialists. In addition, I am very accessible via the web. To schedule your own appointment, call any of the numbers below.

Virginia Lasik | Office of Anh Nguyen, M.D.
Randall V. Wong, M.D.
Contact: Layla

A: 431 Park Avenue, Suite 103 • Falls Church, Virginia 22046
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Randall V. Wong, M.D.
Contact: Ashley (Surgery/Web)
Chrissy Megargee (Web)

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Ph: 703.273.2398
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