New Eye Cancer Treatment Approved

Targeted Sustained Release Drug DeliveryThe FDA just granted Orphan Drug Designation for a new investigati0nal treatment for retinoblastoma.  Retinoblastoma is an eye cancer causing blindness or death in infants and children.

With timely diagnosis, the survival rate for this childhood cancer is quite high, but the morbidity can be devastating.

What is Retinoblastoma?

Retinoblastoma is a congenital eye cancer involving the retina.  It can occur in one eye, both eyes and/or in the brain.  Undetected, it can be fatal.

The tumor occurs in 1/15,000 – 1/20,000 live births.

When involving one eye, there is usually no family history.  Bilateral (involving both eyes) cases and those involving the brain are hereditary and these patients are also at increased risk for developing other types of malignant tumors.

Treatment of the eye involves enucleation (removal of the eye), chemotherapy, freezing, laser or radiation.

Orphan Drug Designation

This FDA designation is not FDA approval, yet is usually given to drugs with the potential to treat rare diseases affecting fewer than 200,000 people in the United States.

The disease affects so few that it is unlikely a company could ever recoup the normal costs of drug development and introducing it into the market.  Special incentives are given which reduce the financial burden, and a rare disease thus has the hope of finding a treatment.

Intraocular Injection

The treatment involves an old drug, melphalen, and a new technology.  The drug is delivered as a sustained release intraocular injection (similar to Ozurdex) attached to a biocompatible compound which slowly releases the drug into the eye over time.

Icon Bioscience, Inc., has developed Verisome®, a patented technology for releasing drugs into the eye involving a biocompatible polymer with unique chemical properties designed for accurate and prolonged time release.  Several other drugs for treatment of eye disease are under development using the same Verisome® technology.

What Does This Mean?

This is an extreme example of the value of targeted sustained drug release for eye disease.

Intraocular injections have given us great success in treating old diseases.  Ozurdex, Avastin, Lucentis and Eylea are all examples of intraocular injections for various retinal diseases.  The injections have become common place over the past 5 years.

Success is due to targeted delivery of the desired drug to the retina.  Intraocular injections have successfully obviated the “blood brain barrier.”  As a rule, drugs taken by mouth or intravenously simply to not penetrate the eye to any substantial level.

By injecting directly into the eye, the drug surpasses the “blood brain barrier” and much needed drug is delivered, or targeted, to the diseased tissue, the retina.  In addition, as in this case, drug will be released for weeks to months (i.e. sustained release) with a single application.  As a result, new “treatments” emerge.

Perhaps a “cure” for this horrible eye cancer develops simply by changing the route of administration, sustained release and an incentive plan from the FDA.


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


Macular Degeneration Treatments

Avastin Treats Cancer, Diabetic Retinopathy and Macular Degeneration

What do they have in common?  Vascular Endothelial Growth Factor (VEGF) happens to be the common denominator between cancer, diabetic retinopathy and “wet” macular degeneration.  Surprising that the latest treatments for the the eye are the same chemotherapy treatments for a variety of cancers?  Does it seem to you that Avastin is used to treat diabetic macular edema, diabetic retinopathy and wet macular degeneration?

Unrestricted Blood Vessels – In macular degeneration, the “wet” form of the disease is defined by the presence of choroidal neovascularization.  These are abnormal blood vessels growing between the layers of the retina.

Cancerous tumors enjoy unrestricted growth.  As the tumors continue their growth, the tissue requires blood supply.  The tumor growth is dependent upon…neovascularization, the growth of new blood vessels.  There are two stages of diabetic retinopathy, non-proliferative and proliferative.  “Proliferative” is defined as the unrestricted growth of…blood vessels.

VEGF – Vascular endothelial growth factor was discovered by cancer researchers in the 1980’s.  A similar protein was long suspected to be integral in the chain of events causing proliferative diabetic retinopathy.  When I was training in the late 1980’s and early 1990’s, we always spoke of a potential protein/agent causing the abnormal proliferation of blood vessels in the eye.

As it turns out, tumors secrete VEGF to allow both the formation and maintenance of the vascular tree.  So too, does the eye in cases of diabetic retinopathy and wet macular degeneration.  The VEGF induces the formation of new blood vessels and keeps them “alive.”  When VEGF is blocked, by anti VEGF medications such as Avastin, the growth of the blood vessels stops and the existing vessels shrivel.

Vascular Endothelial Growth Factor was originally known as vascular permeability factor (VPF).  For our purposes, VPF causes blood vessels to become incompetent, or leaky.  This is the case in diabetic macular edema.  The normal retinal blood vessels leak, causing fluid to accumulate in the retina/macula, leading to decreased vision.  Presumably, by blocking VPF (=VEGF) the vessels stop leaking.  This would explain why, or how, anti-VEGF medications seem to be effective in treating macular edema.

What Does This Mean? Obviously, I am not a cancer researcher, but Avastin is FDA approved for multiple cancers (certain types of brain, lung, kidney, colon, etc.).  It seems that by focusing treatment on the common denominator of all tumore, i.e. blood vessels, a variety of treatments have emerged.  While such targeted chemotherapy is not new in medicine, it is new to ophthalmology.

I wrote today to underscore that it seems that anti-VEGF/Avastin seems to be indicated for every aspect of macular degeneration and diabetic retinopathy.  It is not your imagination, nor your misunderstanding of your reading…it’s true.


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

How I Practice Macular Degeneration Treatments

Standard of Care vs. FDA Approved – How We Choose a Treatment

Avastin® is not FDA (Food and Drug Administration) approved for treating wet macular degeneration, but it is the standard of care for treating the disease.   The FDA has given approval for Avastin to be used to treat a variety of cancers, but nothing about eyes.

What is Standard of Care? Standard of care is the treatment that another prudent healthcare professional, of similar backgrounds and training,  would give to the same patient.  As an example, if I choose to treat you with Lucentis for wet macular degeneration and I am complying with the local standard of care, another retina specialist practicing across the street, would choose the same treatment for you.

What About FDA Approval? Last post, we spoke about evidenced based medicine and the need for a new drug to gain FDA approval.  Once a drug gains FDA approval, it may be used “off-label.”  Off-label indicates that healthcare providers have found other uses for the drug, in addition to the FDA indication.

Avastin is used “off-label” for the treatment of wet macular degeneration.  Avastin has FDA approval for the treatment of certain colon, breast, lung, kidney and brain tumors.

What About Lucentis? Lucentis® is made by the same manufacturer as Avastin (Genentech/Roche).  That manufacturer did go through clinical trials, and costs, of getting FDA approved for wet macular degeneration.

Avastin and Lucentis are chemically very similar, they are cousins.  One is much more expensive than the other.  Both are anti-VEGF treatments.

On Becoming the Standard of Care In this case, several people receiving chemotherapy for colon cancer started reporting that their vision was improving.  Some smart docs paid attention to these comments.  In short, because of the similarities, Avastin was soon used for intraocular injection.

The doctors that pioneered this approach designed a few “randomized” studies and reported their results at our industry meetings.  Others repeated similar studies and were finding the same results.

This then becomes intriguing for community physicians (like yours truly) and we try it ourselves.  If it works, we embrace the new “off-label” treatment.

What Does This Mean? In the case of Lucentis and Avastin, this means that we use a similar drug, get similar (or perhaps even better) results, but significant cost savings.  From a healthcare point of view, while Avastin was never FDA approved, the industry provides its own proof.

This is still evidenced based medicine.  While the traditional FDA clinical trials were not performed, similar trials are usually performed by institutions or groups of doctors that feel a new use, or indication, for a treatment is possible.  The trials are usually shorter and focused on efficacy of the new treatment.  The best “studies” are those that are prospective, randomized and double blinded.  These ensure the accuracy of any results.  The results are presented at meetings and in so-called “peer reviewed” journals.  It is in this arena, that we decide, outside of government (i.e. FDA) sanction, if new treatments are worthwhile.

It is at this level, we read a plethora of “studies” making claims.  There are good and bad studies.  This is where we need to “read critically.”


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

Reblog this post [with Zemanta]
Verified by MonsterInsights