drug delivery Archives - Retina Specialist | Fairfax, Virginia

Iluvien Gets Closer to FDA for Diabetic Retinopathy

Iluvien, an injectable drug delivery system for the treatment of diabetic retinopathy, gets closer to becoming FDA approved. Alimera Sciences announced this week that the FDA has given the investigational device “Priority Review” status. Priority Review status hastens the chances of full FDA endorsement from 10 months to 6 months.

What is Iluvien?

Iluvien is a sustained drug delivery system that is injected into the eye, specifically into the vitreous. Similar to Ozurdex, Iluvien will release steroids into the eye, in this case, up to 3 years. Alimera Sciences anticipates that this drug delivery system will be approved for treating diabetic macular edema, a very common malady that affects those with diabetic retinopathy.

Current Treatment for Diabetic Retinopathy

This approach is novel in that it will be the first pharmaceutical agent, or medicine, to be FDA approved for diabetic macular edema. To date, only laser treatment to the retina is approved.

On the other hand, retina specialists like myself, have been using intravitreal injections of Avastin or steroids for several years as an acceptable alternative to laser.

Other Drug Delivery Systems for the Eye

Ozurdex was released just over a year ago (summer 2009) for the treatment of retinal vein occlusions. Vein occlusions, another type of retinal disease, can cause significant loss of vision. I have had tremendous results using Ozurdex, especially for patients with branch retinal vein occlusions.

There are several other injectable systems under development, not just for diabetes, but for macular degeneration and other eye diseases as well.

What Does This Mean? This is significant news in several ways. First, there is a new therapy emerging for the treatment of the most common complication of diabetic retinopathy. This is a boon for physicians like myself who are tiring of the limits of laser photocoagulation. This system has the promise of making visual improvements not possible with laser.

There is a revolution just beginning in the management of eye disease. These injectable drug delivery systems will forever change our ability to treat, not just retinal disease, but eye disease overall.

Mr. Ozurdex's Vision is Sustained

“Mr. Ozurdex” is a patient in whom I injected Ozurdex® for the treatment of a branch retinal vein occlusion (BRVO). Ozurdex, is the first sustained release drug delivery system for the eye. It was FDA approved for the treatment of retinal vein occlusions last summer (RVO). Allergan began marketing Ozurdex shortly after the FDA approval.

Mr. Ozurdex was given an intraocular injection in early January. Upon his first return visit, he noted a dramatic improvement in his vision! At the time of injection, he was legally blind. After only 2 weeks, his vision improved enough to read.

Upon his return this week, his vision remains stable, he can still read and there are no concerns of any complications. As with any injection of steroid, in increase in eye pressure may occur. Happily, there is none.

Mrs. Ozurdex is Still Worried

“Mrs. Ozurdex,” on the other hand, is still not seeing any differently. About the same time, I injected Ozurdex for treatment of a central retinal vein occlusion (CRVO). There are two types of retinal vein occlusions; central (CRVO) and branch (BRVO).

Mr. “O” had a BRVO. The visual prognosis has always been better with a branch retinal vein occlusion.

Mrs. “O” had a CRVO. The visual prognosis has always been much poorer with a central retinal vein occlusion.

Early Visual Results May be Misleading

I have cautioned both patients. First, with Mr. Ozurdex, while the results are fantastic, the real question is whether or not we can sustain this improvement. He may require another injection of Ozurdex, plain steroid, or even anti-VEGF, such as Avastin.

I have encouraged Mrs. Ozurdex to remain positive. First, she is no worse than when we decided on the sustained release therapy, and second, the drug will be released for several more months to come. There is still a great deal of blood and edema that can resolve, so who is to say how well she’ll fare over the next four months?

What Does This Mean? It is exciting to try a new therapy especially in an area where there have traditionally been few therapeutic options. It is also easy to be biased, good or bad, about the results of a new treatment.

I have no way of really knowing if every patient is going to respond like Mr. “O.” We have yet to define the perfect patient for receiving the new steroid releasing device, perhaps everyone will.

It’s too early to tell if Mrs. “O” is exhibiting a typical or atypical response to Ozurdex given her condition.

Though the FDA has given its approval, it doesn’t necessarily translate into a positive outcome.

Eye Drops for Macular Degeneration

What if there were eye drops for treating your macular degeneration? What if all you had to do was simply use a few drops a day and your vision would get better? There is a “solution” for tired eyes, redness, contact lenses, but what about for your retina?

Eye Drops for Macular Degeneration Sound Compelling

There aren’t any eye drops for macular degeneration or diabetic retinopathy. In fact there are few retinal diseases where they would work at all. Topical drops, just like intravitreal injections, however, are great because the medicine is placed directly where you want it – at the target tissue.

Drops, like eyeglasses, seem to be a panacea. No matter how carefully I explain the prognosis or treatment plan to a patient, I usually get a blank stare (and then I realize noone was listening to me) and then they say the inevitable…”What about eye drops?” or “What about Glasses?”

“Visine” – It Gets the Red Out

Maybe the reason eye drops are held so closely to everyone’s heart is due to “Visine®,” or at least the marketing department of Visine. Everyone knows that famous byline – “it gets the red out.”

A drop that gets red, tired eyes to look refreshed in seconds certainly would get my attention. If there are drops that get your eyes to change appearance, then there must be drops for everything else…right?

Most Drops Work Only on the Outside

There are ocular solutions for;

redness
allergy and itching
infections
dryness (artificial tears)
glaucoma
dilating drops
and for inflammation.

But there are no drops for macular degeneration or diabetic retinopathy for that matter. Eye drops are great for diseases that affect the outside of the eye. So called “topical therapy” typically does not penetrate the eye very well, and it is very difficult to get any significant concentration of drug into the vitreous or to the retina.

Outside of glaucoma, most drops are placed exactly where we want them, on the outside of the eye. Glaucoma drugs have become pretty good (so I’m told) at lowering the pressure inside the eye due to limited penetration of the glaucoma drug.

Most Drugs Never Get Inside the Eye

May be now this makes a bit more sense. Eye drops for macular degeneration sound great, but they just don’t exist. As far as we can tell, we have found the right drugs, but not in a form that has easy an easy time getting to the inside of the eye. Avastin®, Macugen® and Lucentis® are all too large for the molecules to penetrate the ocular surface. Steroids, such as Kenalog® or related anti-inflammatory agents, have poor surface penetration, too. All these drugs, if given as topical eye drops, would simply splash on your eye and run down your cheek…wasted.

What Does This Mean? My comments a few weeks ago about the blood brain barrier and the treatment of retinal disease left out any remarks about topical treatments. Eye drops are great for diseases on the outside of the eye. Just as intravitreal injections are working well for retinal disease due to targeted delivery, so too are eye drops. They are delivered directly to the target issue.

In eye disease, we do have to split hairs. There are vast differences between the outside and inside of the eye. The method we choose to deliver the drugs depends upon what, and where, you are treating.

“Randy”

Randall V. Wong, M.D.

Ophthalmologist, Retina Specialist
Fairfax, Virginia

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.