Macular Degeneration

Macugen: First anti-VEGF Eye Injection….so, Where's Waldo?

Like the image game “Waldo,” Macugen® seems to be lost in a sea of literature about other anti-VEGF intraocular injections.  Macugen was; however, the first intraocular injection for the treatment of wet macular degeneration.  It became FDA approved for the treatment of wet ARMD in 2004.  Where is it now?

The First anti-VEGF Intraocular Injection. Quite simply, this was a significant change for the treatment of retinal disease; specifically diabetic retinopathy and macular degeneration.  Macugen was significant for several reasons; it was the first actual drug designed to treat wet macular degeneration, it was the first ophthalmic anti-VEGF drug designed to treat a disease at the molecular level and it was the first therapeutic drug delivered by intraocular injection.

Prior to Macugen, intraocular injections were not routine, or “state of the art,” treatment for any eye disease.  The immediate success of Macugen, however, changed the way we treated retinal disease.  Direct, intraocular injections are now routine, e.g. Lucentis® and Avastin®.  Ozurdex® (Allergan), a sustained release system, and other similar systems, will also be delivered by………..intraocular injection.

What Does Anti-VEGF Mean? Vascular Endothelial Growth Factor (VEGF) was reviewed yesterday.  It is has several properties that are implicated in the disease process occurring in both diabetic retinopathy and macular degeneration.  VEGF is a protein that is produced by the retina.  VEGF must bind, or “plug in,” to a receptor for it to work.

Anti-VEGF drugs, like Macugen, Lucentis and Avastin, act to prevent VEGF from binding, or “plugging in” to its receptor.  The process is very similar to an antigen and an antibody.  Macugen is actually an “aptamer” against VEGF.  This anti-VEGF aptamer is injected directly into the eye.  It will find, and bind to, any VEGF floating around in the vitreous and retina.  The VEGF is no longer able to link to its receptor………voila, no more damage.

Different Types of VEGF are present throughout the body.  There are actually six different “isoforms” of VEGF.  Macugen was designed only against VEGF 165.  It was well known to cause vascular permeability (vascular leakage) at the time of its design.

So Where is Waldo? (i.e. What Does This Mean?)  I do not use Macugen much anymore.  There are several reasons.  The out of pocket costs to my patients are too high.  Insurance only covers so much of the drug and the rest is out of pocket expenses.  This is the same issue I have with Lucentis.  It costs my patients too much (Medicare only pays 80%).

Most importantly, the results I had with Macugen were not as impressive as Lucentis or Avastin..  One difference may be that Macugen is targeted against only one isoform of VEGF whereas the other drugs target more than VEGF 165.


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

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Macular Degeneration

Diabetic Retinopathy Vs. Macular Degeneration (Part 2 of 2)

Good Morning!  This is part 2 of 2.  Part 1 was posted yesterday.  Read Part 1.

6.  Treatment with Avastin® or other anti-VEGF inhibitors

Technically, both diseases may be treated with anti-VEGF inhibitors.

Presently, I sometimes treat the neovascular component of diabetic retinopathy with Avastin® if pan-retinal laser photocoagulation (standard treatment) fails.  More often, using Avastin® as an off-label drug, I will treat diabetic macular edema that is not responding to laser treatment.

Macular degeneration is usually not treated (most cases are the dry form), whereas the “wet” form of macular degeneration is usually treated with anti-VEGF therapy.

7.  Cataracts are like Grey Hair, Some at an Early Age and Some Later, but Everyone Gets Them

Patients with diabetes usually develop cataracts earlier than the general population.  Remember, cataract surgery is usually best performed when the retinopathy is stable.

There is no proven association between cataract surgery and macular degeneration.  While both do usually occur with advancing age, there is no known cause-effect relationship.

Everyone gets cataracts…………eventually.

8. Macular Edema – “swelling” of the macula

Diabetic macular edema develops from abnormalities of the normal retinal blood vessels.  Normal blood vessels do not leak fluid or blood.  Blood vessels of a diabetic tend to lead over time (say 5-10 years).  When the swelling involves the macula, vision may decrease.  Treatment usually involves laser treatment, but may, these days, also include Avastin®, Lucentis®, Macugen® or steroids.

Swelling of the macula may occur in the “wet,” or exudative, form of macular degeneration.  Abnormal blood vessels (aka neovascularization) can develop underneath the retina and leak or bleed.

9.  Lack of Symptoms and Home Monitoring

A patient with diabetes may develop diabetic retinopathy and not know it.  Vision may be perfect and there are no symptoms.  Home monitoring is not too valuable.  It is best to have regular eye exams with your doctor.

A patient with macular degeneration, by definition, has loss of vision (a symptom).  Thus, patients with known macular degeneration should have at least one symptom (the decreased vision) and should be aware of the disease.  Other symptoms included persistent distortion in the vision.  Home monitoring with the Amsler grid is commonly recommended.

In either case, to make the diagnosis of either macular degeneration or diabetic retinopathy, your doctor should consider evaluation with a flourescein angiogram and OCT.

10  In closing, there are very few souls that have both macular degeneration and diabetic retinopathy.  While this is not a hard fact, it is rare, in my experience, to see a patient with both diseases.  It is as though one protects from the other.  Others have noted this, and I welcome any one’s comments either way.
Read Part 1.


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


Diabetics Get Cataracts

Cataracts are like grey hair…………..everyone gets cataracts, some at an early age and some at a later age.  Period.

Cataracts are generally not inherited (okay, there are some inherited or congenital cataracts seen in kids).  There are many factors that may influence the development of a cataract; ultraviolet rays from the sun, trauma, previous eye surgery and …. diabetes.  While everyone does eventually develop a cataract, patients with diabetes usually develop cataracts earlier.

Cataracts cause symptoms similar to diabetic retinopathy.  Both can cause blurry vision and can be slow and progressive.  It is probably impossible for a patient to distinguish loss of vision from a cataract versus diabetic retinopathy; yet another reason to stay in touch with your eye doctor!

If you have a cataract, it is best to make sure that your diabetic retinopathy is stable before considering cataract surgery. More specifically, if the diabetic macular edema is not controlled at the time of cataract surgery, there is an increased risk that the macular edema will worsen after cataract surgery!  This will cause your vision to get worse and so, too, the relationship with your surgeon.  As I have written previously, there are treatments for macular edema including laser photocoagulation, intravitreal injections of steroid and injections of anti-VEGF drugs such as Avastin ™, Lucentis™ or Macugen™.  Read more about standard treatments for diabetic macular edema.

It is probably best to try and avoid worsening macular edema altogether. With most patients, cataract surgery is postponed as long as tolerable, but in patients with diabetes, I would recommend getting cataract surgery earlier, if the diabetic retinopathy is stable.  Another way of stating the timing of cataract surgery would be; if the retinopathy is stable, then one should consider cataract surgery earlier than in a non-diabetic situation, in an attempt to avoid complications from the diabetic retinopathy.

Read more about “When is a Cataract ‘Ripe?'”


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

Macular Degeneration Retina

Cases of ARMD to Double

In this month’s (April,  2009) edition of Archives of Ophthalmology, a study reports the prevalence of patients afflicted with macular degeneration is expected to almost double by the year 2050.  In other words, the number of patients suffering the disease at a given time is expected to near double in the next 40 years.

All forms of macular degeneration are expected to increase over the next 40 years.  There are two major types of macular degeneration; dry and wet.  The most common form of macular degeneration is the “dry” form (also known as non-exudative macular degeneration).  The most aggressive form of macular degeneration is the “wet” form (also known as exudative macular degeneration).  Significant vision loss may result in either type, although the dry form  usually progresses much more slowly.

There is good news.  The report also predicts that the use of antioxidant supplements will significantly reduce the amount of vision loss as our population ages, that is, current advances in supplements seem to be helping.

Currently there is no approved treatment for dry macular degeneration.  Patients with wet macular degeneration often receive injections into their eye of medications called VEGF (Vascular Endothelial Growth Factor) inhibitors such as; Lucentis®, Avastin® and Macugen®.

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

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