Northeast Wisconsin Retina Associates

Surgical Procedures

INTRAOCULAR INJECTION OF MEDICATIONS

Injection of medication into the eye has been an accepted form of treatment for many years. For decades, retinal specialists have used this approach to treat serious infections such as those that can occur following cataract surgery. During the past decade, dramatic advances have been made in the therapy of many common retinal and macular conditions by injecting various drugs directly into the eye. This technique is called intraocular (or intra­vitreal) injection of medications.

Currently, two types of medications are commonly used: 1) steroid medications and 2) drugs that block the effect of vascular endothelial growth factor, so-called anti-VEGF medications (discussed in detail below). Both types of medications are used primarily to treat macular diseases which cause swelling (edema) of the macula or conditions that lead to abnormal blood vessel growth beneath the macula (choroidal neovascularization, CNV). Diabetic macular edema and retinal vein occlusion are the most common disorders that cause swelling of the macula whereas age-related macular degeneration is the cause of most cases of CNV. There are many other less common conditions which also respond favorably with intraocular injection of medications. Additional discussions regarding diabetic macular edema, retinal vein occlusion and age-related macular degeneration are provided in Clinical Conditions.

Intraocular medication injections are typically performed in the retinal specialist’s office. The surface of the eye and injection site are anesthetized (numbed) with a local anesthetic medication. A number of precautions are taken to minimize the number of normal bacteria present on the surface tissue of the eye and the lid margins where the eyelash follicles are found. The injection is then performed through the white portion of the eye delivering the medication into the vitreous. See Clinical Conditions: Anatomy and Function of the Eye. Treatment is generally quite well tolerated. Some patients will note mild irritation the day of an injection, however it is typically possible to resume routine activities immediately and there are no significant limitations or restrictions postoperatively.

Information Regarding Anti-VEGF drugs

Background

We have recently entered a new era in the treatment of a number of common retinal disorders such as the wet form of age-related macular degeneration (wet AMD), diabetic retinopathy and retinal vein occlusions. It is now well-established that a chemical called vascular endothelial growth factor (VEGF) is one of the main mediators secreted in the eye that is responsible for the complications and visions loss associated with these conditions. VEGF has effects in other parts of the body and has also been shown to be involved in the growth of certain tumors.

Fortunately, over the last decade, major advances have been made in the understanding and treatment of eye diseases mediated (at least in part) by VEGF.

Drugs have been developed to block the effect of VEGF (anti-VEGF medications) and have found a variety of applications in medicine – from treating certain cancers to eye diseases including AMD. Since 2006, injection of anti-VEGF medications into the eye has become a mainstay of therapy for wet AMD, some complications of diabetic retinopathy, retinal vein occlusions and a variety of other retinal/macular disorders.

Indications

Anti-VEGF medications have been a revolutionary advance in the treatment of many retinal/macular disorders. The two most common applications involve the treatment of conditions that result in the growth of abnormal blood vessels beneath the macula (such as age-related macular degeneration) or swelling (edema) of the macula (as in the case of diabetic retinopathy and retinal vein occlusion). Specific examples include:

1. Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 years of age. It is caused by the breakdown of the central portion of the retina (the nerve tissue lining the inside of the eye) call the macula. The macula is responsible for fine central vision that is needed for driving a car, reading fine print, recognizing faces, etc. There are two types of macular degeneration: dry and wet (advanced, severe). In the “wet” form of AMD, abnormal blood vessels (known as choroidal neovascularization or CNV) grow beneath the macula. These vessels leak blood and/or fluid causing blurred or distorted vision. Without treatment, vision loss is often rapid, severe and permanent.

2. There are many other eye conditions that can cause growth of abnormal blood vessels beneath the macula (CNV). These conditions can occur even in young patients, and include, but are not limited to, high myopia (nearsightedness), histoplasmosis, angioid streaks, and certain eye injuries. Sometimes there is no known reason for the formation of these abnormal blood vessels. Without treatment these disorders can also cause serious vision loss.

3. Macular edema is swelling of the macula that causes loss of central vision. It can occur with conditions such as retinal vein occlusion and diabetic retinopathy. Without effective treatment, vision loss can progress and become permanent.

4. Proliferative retinopathy can occur in association with a variety of conditions including diabetic retinopathy, retinal vein occlusion and retinal artery occlusion and can lead to bleeding inside the eye and loss of vision.

5. Neovascular glaucoma is a severe form of glaucoma (elevated eye pressure) that can occur in association with proliferative diabetic retinopathy, retinal vein occlusion and retinal artery occlusion.

6. Anti-VEGF medications are also used in some cases of proliferative diabetic retinopathy prior to performing vitrectomy surgery.

7. Retinopathy of prematurity (ROP) in extremely premature infants has been treated with considerable success using anti-VEGF medications.

Expectations regarding treatment

The main goal of treatment with anti-VEGF medications for eye disease is to prevent further loss of vision. As mentioned above, the most common indication for treatment is the wet form of age-related macular degeneration (wet AMD). Although some patients may have significant improvement in vision, this occurs in only a minority (approximately 35%). Even with ongoing therapy, treatment may not ultimately prevent further loss of vision caused by the underlying disease process.

As with any treatment, there are certain inherent limitations. In the case of anti-VEGF medication therapy for eye disease, patients and their families should understand that conditions such age-related macular degeneration (AMD) and diabetic retinopathy are chronic diseases. Although our newer treatment modalities often prove to be highly successful, no cure is available. Most patients with these diseases will require ongoing treatment at varying frequencies over the long term. On the other hand, the dramatic advances provided by anti-VEGF medications over the past several years have allowed many of our patients to maintain a much higher level of independence and quality of life as compared with previous treatment options.

Administration

Intraocular medication injections are typically performed in the retinal specialist’s office. The pupil is dilated. The surface of the eye and injection site are anesthetized (numbed) with a local anesthetic medication. A number of precautions are taken to minimize the number of normal bacteria present on the surface tissue of the eye and the lid margins where eyelash follicles are found. The injection is then performed through the white portion of the eye, delivering the medication into the main chamber of the eye which contains vitreous (a clear jelly-like substance). This is called an intraocular or intravitreal injection.

Treatment is generally quite well tolerated. Most patients will note mild irritation the day of any injection. However, it is typically possible to resume routine activities quickly and there are no significant limitations or restrictions postoperatively.

Medication injections are often administered at regular intervals (4-8 weeks). The number of injections necessary and duration of treatment may vary considerably depending upon the disease being teated, the individual patient response, and other factors.

Anti-VEGF medications for eye disease

There are currently four anti-VEGF drugs that can be used to treat eye disease. They are:

  1. Macugen
    • The “first generation” drug which has been replaced by much more effective medications
  2. Avastin
    • Originally developed to treat advanced stages of colorectal cancer
    • Adapted to the treatment of eye disease and widespread (worldwide) use by retinal specialists began in 2005
  3. Lucentis
    • Introduced in 2006 and derived from Avastin
    • Manufactured by the same company which produces Avastin
    • Marketed exclusively for the treatment of eye disease
    • In early 2011, the results of a large clinical trial providing a direct comparison between Avastin and Lucentis were published. This study, the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), demonstrated equivalent efficacy between the two drugs.
  4. Eylea
    • Available as of December 2011
    • Clinical trials comparing Lucentis with Eylea demonstrate identical efficacy between the two drugs in the treatment of Age-Related Macular Degeneration.

The choice of which drug to use in the treatment of any given patient is complex and a complete discussion of these considerations is beyond the scope of this informational material.

Comparison of Anti-VEGF Medications

AvastinLucentisEylea
FDA-approved for wet AMDnoyesyes
Reimbursable through Medicareyesyesyes
Track record with regard to safety/efficacy thru clinical trialsyesyesyes
Frequency of administration (weeks)4-644-8
Potential for stabilizing visionGoodGoodGood
Cost per dose$$$$$$$$$

FDA-approved uses and “Off-Label” Status

Based upon results of clinical trials demonstrating safety and efficacy, the Food and Drug Administration (FDA) may approve a drug to be marketed for the treatment of a specific condition. This only occurs when the manufacturer actively pursues the costly and lengthy approval process. As a condition for such approval, the manufacturer produces a “label” explaining the indications, risk and benefits for use.

Once a device or medication is approved by the FDA and brought to market, physicians may use it “off-label” for other purposes if they are well-informed about the product, base its use on firm scientific method and sound medical evidence, and maintain appropriate records. For years, retinal specialists have been using anti-VEGF medications “off-label” to treat a variety of serious, potentially blinding retinal/macular conditions. This has proven to be both safe and effective and is currently considered “standard of care.”

Potential Complications

1. Ocular complications (damage to eye/vision)

Possible complications and side effects of intraocular injection of anti-VEGF medications include, but are not limited to, retinal detachment, cataract formation (clouding of the lens of the eye), glaucoma (increased pressure in the eye), and bleeding. There is also the possibility of infection in the treated eye (endophthalmitis). Any of these rare complications may necessitate additional surgery and could lead to serious and even permanent loss of vision.

2. Systemic

As mentioned previously, Avastin was initially developed for treating patients with advanced stages of colon cancer. Clinical trials in this setting (as well as in the studies of breast cancer patients) demonstrated an increased risk of stroke, heart attack and high blood pressure as well as complications following surgery, such as impaired wound healing. It is important to recognize that the patients who experienced these complications were already very ill and were also being treated intravenously (spreading the drug throughout the entire body) and with enormous doses (400 times that used to treat the eye).

Despite theoretical concerns regarding these issues in the treatment of eye disease with anti-VEGF medications, numerous large studies have failed to demonstrate such side effects. Of course, even after years of experience and many hundreds of thousands of treatments administered worldwide, the risks and benefits of long-term therapy cannot be fully known.

Finally, whenever a medication is used in a large group of patients, a small number of coincidental life-threatening problems can occur that may have no relationship to the treatment itself. For example, patients with diabetes are already at increased risk for heart attack and stroke. If one of these patients being treated with an anti-VEGF medication suffers a heart attack or stroke, it may be related to the diabetes and not the anti-VEGF medication.

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