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Treatment of Diabetic Retinopathy
and Macular Edema

By Marilyn Haddrill, with contributions and review by Charles Slonim, MD

Millions of Americans each year face vision loss related to diabetes. In fact, according to recent data from the U.S. Centers for Disease Control and Prevention (CDC), nearly 26 million Americans — roughly 8.3 percent of the U.S. population — have diabetes, and more than 28 percent of diabetics age 40 or older in the U.S. have diabetic retinopathy (DR) and related diabetic eye disease.

To make matters worse, a significant number of cases of diabetes and diabetic eye disease go undetected or untreated because people fail to have routine comprehensive eye exams as recommended by their optometrist or ophthalmologist.

Most laser and non-laser treatments for diabetic eye disease depend on the severity of the eye changes and type of vision problems you have.

To better understand the treatments, you first must know how the eye is damaged when you have diabetes. Diabetic retinopathy typically is a disease of the tiny blood vessels that supply oxygen and nourishment to the retinal tissues (retinal microvasculature). This retinal microvascular damage leads to poor blood flow — which can cause localized fluid accumulation (edema) and lack of oxygen in the retina.

Research also has shown that the retinas in diabetic patients may produce abnormal amounts of vascular endothelial growth factors (VEGF), which stimulate the production of abnormal blood vessels — a process called neovascularization.

The blood vessels produced by this process are fragile and can easily break open, leaking blood and other blood products such as proteins into the back of the eye, obscuring vision.

Diabetic retinopathy can cause swelling and fluid accumulation in the macula, which is a small area in the central retina that is responsible for our most acute vision. Proper functioning of the macula is essential for tasks such as driving a car, watching TV, working at a computer and reading.

Swelling of the macula from diabetes — called diabetic macular edema (DME) — is the most common cause of vision loss among diabetics and is the leading cause of new cases of blindness in adults 20 to 74 years old in the United States, according to CDC.

Lasers for Diabetic Retinopathy Treatment

Laser treatment of diabetic eye disease generally targets the damaged eye tissue. Some lasers treat leaking blood vessels directly by "spot welding" and sealing the area of leakage (photocoagulation). Other lasers eliminate abnormal blood vessels that form from neovascularization.

Lasers also may be used to destroy the peripheral parts of the normal retina that are not involved in seeing. This is done to help maintain vision in the central portion of the retina.

If you have a diabetic vitreous hemorrhage, you may require a vitrectomy to remove the clear, gel-like substance in your eye's interior.

The peripheral retina also is thought to be involved in formation of VEGF responsible for abnormal blood vessel formation. When the peripheral retina is destroyed through panretinal photocoagulation (see below), the amount of VEGF is reduced, along with the potential to produce abnormal retinal blood vessels.

After these outermost cells in the retina are destroyed, blood flow also bypasses this region and instead provides extra nourishment to the central portion of the retina responsible for extra sharp vision. The extra boost of nutrients and oxygen then helps nurture this essential central portion of the retina. However, some peripheral vision could be lost due to this treatment.

The two types of laser treatments commonly used to treat significant diabetic eye disease are:

• Focal or grid laser photocoagulation. This type of laser energy is aimed directly at the affected area or applied in a contained, grid-like pattern to destroy damaged eye tissue and clear away scars that contribute to blind spots and vision loss. This method of laser treatment generally targets specific, individual blood vessels.
• Scatter (panretinal) laser photocoagulation. With this method, about 1,200 to 1,800 tiny spots of laser energy are applied to the outermost (peripheral) regions of the retina, leaving the inner portion untouched.

Treatment of clinically significant DME also entails using fluorescein angiography to provide images of the eye's interior. These images accurately guide application of laser energy, which helps "dry up" the localized swelling in the macula. A fluorescein angiogram also can identify the location of blood vessel leakage caused by proliferative diabetic retinopathy.

While laser treatment for diabetic retinopathy usually does not improve vision, the therapy is designed to prevent further vision loss. Even people with 20/20 vision who meet treatment guidelines should be considered for laser therapy to prevent eventual vision loss related to diabetes.

What To Expect Before, During and After Laser Treatment

Laser treatment typically requires no overnight hospital stay, so you will be treated on an outpatient basis in a clinic or in the eye doctor's office.

Make sure you have someone drive you to and from the office or clinic on the day you have the procedure. Also, you'll need to wear sunglasses afterward because your eyes will be temporarily dilated and light sensitive.

During photocoagulation, heat from a high energy laser seals off bleeding in damaged eye tissue.

Before the procedure, you will receive a topical anesthetic or possibly an injection adjacent to the eye to numb it and prevent it from moving during the laser treatment.

Your eye doctor will make these types of adjustments to the laser beam before it is aimed into the eye:

• The amount of energy used
• The size of the "spot" or end of the beam that is directed into the eye
• The pattern applied by the laser beam onto the targeted area

A laser treatment typically lasts at least several minutes, but more time may be required depending on the extent of your eye condition.

During laser treatment, you might experience some discomfort, but you should feel no pain. Right after a treatment, you should be able to resume normal activities. You might have some discomfort and blurry vision for a day or two after each laser treatment.

The number of treatments you need will depend on your eye condition and extent of damage. People with clinically significant diabetic macular edema may require three to four different laser sessions at two- to four-month intervals to stop the macular swelling.

Though the specific mechanism by which laser photocoagulation reduces diabetic macular edema is not fully understood, a landmark study called the Early Treatment Diabetic Retinopathy Study (ETDRS) showed that focal (direct/grid) photocoagulation reduces moderate vision loss caused by DME by 50 percent or more.

In December 2011, Iridex Corporation announced the results of a 10-year study of the company's MicroPulse laser therapy for treating DME. The study data showed the new micropulse technology was at least as effective as conventional laser photocoagulation in the treatment of macular edema, with less risk of thermal damage and scarring to the surrounding retinal tissue.

If you have proliferative diabetic retinopathy (PDR) — meaning that leakage of fluid has begun in the retina — the laser treatment should take from 30 to 45 minutes per session, and you may require up to three or four sessions.

Your chance of preserving your remaining vision when you have PDR improves if you receive scatter laser photocoagulation as soon as possible following diagnosis.

Early treatment of PDR particularly is effective when macular edema also is present.

Non-Laser Diabetic Retinopathy Treatment

Steroids injected directly into the eye (intraocular steroids) also sometimes are administered in addition to laser treatment to help reduce fluids that accumulate in the retina.

In this video, an eye doctor explains diabetic eye disease. (Video: National Eye Institute)


In this video, Rep. James Clyburn asks African-American diabetics to get annual eye exams.

Based on positive clinical trial results, Alimera Sciences (Alpharetta, Ga.) in June 2010 submitted a new drug application to the FDA for approval of an intravitreal insert called Iluvien.

Although the drug was granted priority review status, approval was delayed in late 2010 because of an FDA request for additional data.

Injected directly into the eye, the insert is designed specifically for treatment of diabetic macular edema and contains a corticosteroid (fluocinolone acetonide) that helps reduce swelling and inflammation.

The insert is held in place by the pressure of eye's clear, gel-like fluid known as the vitreous.

In late-stage clinical trials for Iluvien, about 40 percent of 123 participants with DME had vision improvement after 30 months of treatment. While treatment of this type commonly causes steroid-induced cataracts, surgery typically restores visual acuity. Steroid-induced glaucoma also is a common side effect of intravitreal steroid implants. If needed, treatments may include glaucoma eye drops, lasers or even glaucoma surgery.

Other commercially available intravitreal steroid implants that may be used off label include Retisert (Bausch + Lomb Pharmaceuticals, Rochester, N.Y.) and Ozurdex (Allergan, Irvine, Calif.). Retisert contains fluocinolone acetonide, and Ozurdex contains dexamethasone. However, neither of these implants have specific FDA approval for diabetic macular edema.

Some experimental treatments (see section below) also are being investigated that involve injecting anti-VEGF drugs into the eye to prevent formation of abnormal blood vessels that can cause scarring and blind spots (scotoma).

Vitrectomy and Other Surgery Treatments for Diabetic Eye Disease

In some people who have PDR, bleeding into the vitreous (vitreous hemorrhage) prevents the ophthalmologist from performing the laser treatment. This means the blood blocks the laser beam.

If the vitreous hemorrhage fails to clear within a few weeks or months, a vitrectomy surgery may be performed to mechanically remove the hemorrhage — after which, laser photocoagulation can be applied. The laser procedure is performed either at the time of the vitrectomy or shortly thereafter.

Retinal bleeding and vitreous hemorrhage also can cause bands of scar tissue to form. These bands of scar tissue can shrink and — if attached to the retina — can cause the retina to pull away from its base to create traction.

This traction may lead to retinal tears or possible retinal detachments.

If you experience a tractional detached retina as part of PDR and shrinking scar tissue that tugs at the retina, you usually will be scheduled promptly for a procedure to reattach the retina.

ETDRS guidelines show that type 2 diabetics in particular can reduce their chance of severe vision loss and the need for vitrectomy surgery by about 50 percent when proliferative diabetic retinopathy is treated before it reaches a high-risk stage.

Experimental Treatments for Diabetic Eye Disease

Due to the continuing growth of diabetes and the increasing number of people at risk for vision loss from diabetic eye disease, many companies are actively involved in developing new treatments for diabetic retinopathy and macular edema.

Medications that are showing some promise for the treatment of diabetic eye disease are called anti-VEGF (vascular endothelial growth factor) drugs. These medicines, which are injected into the eye, also are used to treat advanced age-related macular degeneration.

One such drug, Lucentis (ranibizumab), is marketed by Genentech. After one year, Lucentis was found in the Diabetic Retinopathy Clinical Research Network study to significantly improve vision in 50 percent of participants when used in combination with laser therapy. Among those receiving laser therapy alone, only 28 percent experienced significant vision improvement.

In March 2011, Genentech officials announced results of a late-stage clinical trial showing that participants with diabetic macular edema had a significantly better chance of vision improvement when they were treated with Lucentis.

Another anti-VEGF drug, known as VEGF Trap-Eye, is being co-developed by Regeneron Pharmaceuticals and Bayer HealthCare. After promising early study results, the companies announced in April 2011 that Bayer has initiated a late-stage clinical trial of VEGF Trap-Eye in Australia for the treatment of diabetic macular edema. The trial also will be conducted in Europe and Japan.

A second study of VEGF Trap-Eye for the treatment for DME led by Regeneron is expected to begin later in 2011 in the United States, Canada and other countries. The companies also are conducting clinical studies of VEGF Trap-Eye (also called Eylea) for the treatment of central retinal vein occlusion (CRVO), a type of eye stroke. In November 2011 Eylea gained FDA approval for treatment of neovascular ("wet") macular degeneration.

University of Georgia researchers announced in early 2011 that experiments using diabetic rats show a statin anti-cholesterol drug (Lipitor) helped prevent damage from diabetic retinopathy by blocking formation of free radicals and protecting neurons in the retina.

Early study results from another experimental treatment known as NCX 434 (NicOx) were announced in June 2010 at the Retina International World Congress in Stresa, Italy.

The company describes the treatment as a "nitric oxide (NO)-donating new molecular entity" capable of reducing retinal damage related to lack of blood and oxygen (ischemia) caused by diabetic macular edema.

Also in June 2010, Eyetech announced positive late-stage clinical trial results for its anti-VEGF drug, Macugen (pegaptanib sodium).

At 54 weeks, 37 percent of study participants with diabetic macular edema improved visual acuity by at least two lines on an eye chart, compared with 20 percent who received a placebo injection. Researchers enrolled 260 participants for the study.

In the major ACCORD Eye Study sponsored by the National Institutes of Health, extensive blood sugar control combined with cholesterol-lowering drugs reduced the progression of diabetic eye disease by about one-third over a four-year period. Results of the eye portion of the study involving 2,856 people were announced in April 2010.

Chris A. Knobbe, MD, and Gary Heiting, OD, also contributed to this article.

Resources:

National Diabetes Fact Sheet: National estimates and general information on diabetes and prediabetes in the United States, 2011. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. 2011.

Diabetic retinopathy. Cleveland Clinic: Current Clinical Medicine, 2nd ed. 2010.

Serous detachment of the neural retina. Ophthalmology, 3rd ed. 2008.

Effects of intensive glucose lowering in type 2 diabetes. New England Journal of Medicine. July 2010.

Comparison of the Modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Archives of Ophthalmology. April 2007.

Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode micropulse photocoagulation for retinovascular macular edema. Retina. Published online ahead of print, November 2011.

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[Page updated December 2011]