Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Diabetic Retinopathy

Sometimes called diabetic eye disease.

What is Diabetic Retinopathy?

• Diabetic retinopathy is a condition that occurs in people who have diabetes. It causes progressive damage to the retina, the light-sensitive lining at the back of the eye. Diabetic retinopathy is a serious sight-threatening complication of diabetes.​
• Diabetes interferes with the body’s ability to use and store sugar (glucose). The disease is characterized by too much sugar in the blood, which can cause damage throughout the body, including the eyes. ​
• Over time, diabetes damages the blood vessels in the retina. Diabetic retinopathy occurs when these tiny blood vessels leak blood and other fluids. This causes the retinal tissue to swell, resulting in cloudy or blurred vision. The condition usually affects both eyes. The longer a person has diabetes, the more likely they will develop diabetic retinopathy. If left untreated, diabetic retinopathy can cause blindness.​
• The retina is a light-sensitive nerve tissue at the back of the eye. The retina converts the light rays that enter the eye into electrical impulses that travel along the optic nerve to the brain. Too much blood glucose can destroy the blood vessels in the back of the eye, preventing the retina from receiving the proper amount of nutrients it needs to maintain vision.
• Diabetic retinopathy is one of several common eye diseases but is the most common cause of vision impairment and blindness among working-age adults in the United States.
• The disease is categorized into two distinct types:
  • ​​Non-proliferative diabetic retinopathy (NPDR) is the early stage of the disease in which symptoms will be mild or nonexistent. In NPDR, the blood vessels in the retina are weakened. Tiny bulges in the blood vessels, called microaneurysms, may leak fluid into the retina. This leakage may lead to swelling of the macula.​
  • Proliferative diabetic retinopathy (PDR) is the more advanced form of the disease. At this stage, circulation problems deprive the retina of oxygen. As a result new, fragile blood vessels can begin to grow in the retina and into the vitreous, the gel-like fluid that fills the back of the eye. The new blood vessels may leak blood into the vitreous, clouding vision.​

How Do You Get It?

• Unfortunately, almost 80 percent of all patients who have diabetes for more than 10 years, will be affected by this systemic disease. The chance of developing diabetic retinopathy will also increase the longer a patient has diabetes.​
• From 2010 to 2050, the number of Americans with diabetic retinopathy is expected to nearly double, from 7.7 million to 14.6 million.​
• DME can occur at any stage of DR as the blood vessels in the retina become increasingly fragile and leak fluid, potentially causing visual impairment. In the U.S., approximately 1.5 million adults are diagnosed with DME, while approximately 3.5 million people suffer from DR without DME.​
• In 2015, 30.3 million Americans, or 9.4% of the population, had diabetes.
  • Only 23.1 million were diagnosed
• Diabetes remains the 7th leading cause of death in the United States in 2015, with 79,535 death certificates listing it as the underlying cause of death, and a total of 252,806 death certificates listing diabetes as an underlying or contributing cause of death.​
• Diabetic retinopathy results from the damage diabetes causes to the small blood vessels located in the retina. These damaged blood vessels can cause vision loss.
  • Fluid can leak into the macula, the area of the retina responsible for clear central vision. Although small, the macula is the part of the retina that allows us to see colors and fine detail. The fluid causes the macula to swell, resulting in blurred vision.​
    
  • In an attempt to improve blood circulation in the retina, new blood vessels may form on its surface. These fragile, abnormal blood vessels can leak blood into the back of the eye and block vision.​
• Risk factors for diabetic retinopathy include:
  • Diabetes. People with type 1 or type 2 diabetes are at risk for developing diabetic retinopathy. The longer a person has diabetes, the more likely he or she is to develop diabetic retinopathy, particularly if the diabetes is poorly controlled.​
  • Race. Latin Americans and Black people are at greater risk for developing diabetic retinopathy.​
  • Medical conditions. People with other medical conditions, such as high blood pressure and high cholesterol, are at greater risk.
  • Pregnancy. Pregnant people face a higher risk of developing diabetes and diabetic retinopathy. If a female develops gestational diabetes, she has a higher risk of developing diabetes as she ages.​
• Several factors influence whether you get retinopathy:​
  • blood sugar control- People who keep their blood sugar levels closer to normal are less likely to have retinopathy or to have milder forms.​
  • blood pressure levels​
  • how long you have had diabetes​
  • genes​
• The longer you’ve had diabetes, the more likely you are to have retinopathy. Almost everyone with type 1 diabetes will eventually have non-proliferative retinopathy and most people with type 2 diabetes will also get it. But the retinopathy that destroys vision, proliferative retinopathy, is far less common.​
• Your retina can be badly damaged before you notice any change in vision. Most people with non-proliferative retinopathy have no symptoms. Even with proliferative retinopathy, the more dangerous form, people sometimes have no symptoms until it is too late to treat them. For this reason, you should have your eyes examined regularly by an eye care professional if you have diabetes.​

What Are The Symptoms?

• Symptoms of diabetic retinopathy include:
  • Seeing spots or floaters​
  • Blurred vision​
  • Having a dark or empty spot in the center of your vision​
  • Difficulty seeing well at night​
• If left untreated, diabetic retinopathy can cause blindness.​
• Vision loss in diabetic retinopathy is sometimes irreversible. However, early detection and treatment can reduce the risk of blindness by 95 percent.​
• In all, the researchers found, DR was responsible for one of every 39 cases of blindness and one of every 52 cases of visual impairment in 2010.​

How Is It Treated?

• Treatment for diabetic retinopathy depends on the stage of the disease. The goal of any treatment is to slow or stop the progression of the disease
• Huge strides have been made in the treatment of diabetic retinopathy. Treatments such as scatter photocoagulation, focal photocoagulation, and vitrectomy prevent blindness in most people. The sooner retinopathy is diagnosed, the more likely these treatments will be successful. The best results occur when sight is still normal.​
• Treatment of diabetic macular edema (swelling or the accumulation of blood and fluids in the macula, the part of the retina that provides sharp central vision), has evolved a great deal in the last five to ten years and is based on the severity of the edema. At present, there are three options: laser treatment; Avastin, Lucentis, or Eylea injection; intravitreal steroids: Kenalog, Ozurdex, and Iluvien​
• Photocoagulation
  • Laser photocoagulation uses the heat from a laser to seal or destroy abnormal, leaking blood vessels in the retina. ​
  • Focal photocoagulation. Focal treatment is used to seal specific leaking blood vessels in a small area of the retina, usually near the macula. The ophthalmologist identifies individual blood vessels for treatment and makes a limited number of laser burns to seal them off.
  • ​Scatter (pan-retinal) photocoagulation. Scatter treatment is used to slow the growth of new abnormal blood vessels that have developed over a wider area of the retina. The ophthalmologist may make hundreds of laser burns on the retina to stop the blood vessels from growing. The person may need two or more treatment sessions.​
  • Laser photocoagulation is usually not painful. The injection of anesthetic may be uncomfortable. And then you may feel a slight stinging sensation or see brief flashes of light when the laser is applied to your eye.​
• Intravitreal steroids
  • Steroids are very good at treating the swelling caused by diabetic macular edema. Like Avastin, Lucentis, and Eylea, the steroid is injected into the vitreous, the jelly-like substance that fills the inside of the back part of the eye (intra = into; vitreal = vitreous gel). Steroids are powerful drugs that can reduce retinal edema dramatically; however, they also have side effects that can be significant.​
  • The use of steroids to treat eye disease is associated with the development of glaucoma and cataracts in some patients. Nevertheless, steroid treatment can be a useful tool and can be combined with both anti-VEGF injections and laser to control difficult cases of diabetic macular edema.​
  • In the past, steroids were injected in crystalline form into the eye and then were gradually absorbed by the body over 4-6 weeks.​
  • There are now two new steroid medications that have been FDA-approved for the treatment of diabetic macular edema that can deliver drugs to the eye for a much longer period of time. The steroid medications currently available are:​
    • Kenalog (generic name triamcinolone): crystalline solution
    • Ozurdex (generic name dexamethasone): implant injected in the doctor’s office that is active for 3-4 months​
    • Iluvien (generic name fluocinolone acetonide): implant injected in the doctor’s office that is active for up to 36 months. This medication currently is approved only for the treatment of diabetic macular edema in patients who have been treated previously with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure (IOP)​
• In diabetic eye disease, abnormal blood vessels develop that can break, bleed, and leak fluid. If left untreated, these damaged blood vessels can result in a rapid and severe loss of vision. ​
• The most effective treatments to date for this blood vessel damage are the anti-angiogenic drugs Avastin, Lucentis, and Eylea.
  • The focus of current anti-angiogenic drug treatments for diabetic eye disease is to reduce the level of a particular protein, called vascular endothelial growth factor or VEGF, that stimulates abnormal blood vessel growth in the retina; thus, these drugs are classified as anti-VEGF treatments.​​
  • These medications work by blocking a substance known as vascular endothelial growth factor or VEGF. Blocking or slowing VEGF helps prevent further growth of the blood vessels that the cancer needs to continue growing.​
  • At present, Avastin, Lucentis, and Eylea are administered by injection directly into the eye after the surface has been numbed. The needle is very small and is inserted near the corner of the eye – not the center. During the injection procedure, the doctor will ask the patient to look in the opposite direction to expose the injection site, which also allows the patient to avoid seeing the needle.​
  • These drugs are powerful. The abnormal vessels will disappear within 24 to 48 hours; however, the vessels are not gone forever. They will come back, since the effect of the drug will wear off. The half-life of the drugs in the eye is about four to six weeks. Treating edema with these drugs requires frequent injections.
  • Ranibizumab is a vascular endothelial growth factor-A (VEGF-A) inhibitor.  VEGF-A causes neovascularization and leakage in patients of ocular angiogenesis, vascular occlusion and contributes to the neovascular form of age-related macular degeneration (AMD) progression. The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.​
  • Avastin
    • Avastin® is a drug used to treat wet age-related macular degeneration (AMD). It is also used to treat diabetic eye disease and other problems of the retina. It is injected into the eye to help slow vision loss from these diseases.​
    • Avastin is the brand name for the drug, which is called bevacizumab. It blocks the growth of abnormal blood vessels in the back of the eye. Those blood vessels can leak and affect vision, causing vision loss from wet AMD and diabetic eye disease.​
    • Avastin was first approved by the Food and Drug Administration (FDA) to treat different types of cancer. Its use to treat eye disease is considered “off-label” use. The FDA allows “off-label” drug use if doctors are well informed about the product and studies prove the drug is helpful.​
  • Eylea (aflibercept)
    • Officially cleared for all stages of diabetic retinopathy by the FDA in 2019
• Prevention is key
• If you are diabetic, you can help prevent or slow the development of diabetic retinopathy by:
  • Taking your prescribed medication​
  • Sticking to your diet​
  • Exercising regularly​
  • Controlling high blood pressure​
  • Avoiding alcohol and smoking​
• Non-drug treatments
  • Laser surgery is often helpful in treating diabetic retinopathy. To reduce macular edema, a laser is focused on the damaged retina to seal leaking retinal vessels. For abnormal blood vessel growth (neovascularization), the laser treatments are delivered over the peripheral retina. The small laser scars that result will reduce abnormal blood vessel growth and help bond the retina to the back of your eye, thus preventing retinal detachment. Laser surgery may be performed in your ophthalmologist’s office or in an outpatient clinic. Laser surgery can greatly reduce the chance of severe visual impairment.​
  • Vitrectomy may be recommended in advanced proliferative diabetic retinopathy. During this microsurgical procedure that is performed in the operating room, the blood-filled vitreous is removed and replaced with a clear solution. Your ophthalmologist may wait several months to a year to see if the blood will clear on its own before going ahead with surgery. In addition to a vitrectomy, retinal repair may be necessary if scar tissue has detached the retina from the back of your eye. Severe loss of vision or even blindness can result if surgery is not performed to reattach the retina. ​
    • Also used for the treatment of retinal detachment

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this disease from the American Diabetes Association.