Diabetic Retinopathy

Diabetic retinopathy refers to problems with the retina (the light-sensitive tissue at the back of the eye) that can develop in people with diabetes. Caused by changes in the blood vessels of the retina, it is the most common diabetic eye disease and is a leading cause of blindness in American adults.^[1]. If the changes are detected early, they are more likely to be curable, which is why guidelines for diabetics call for yearly eye examinations. Research suggests that the severity and progression of diabetic retinopathy can be decreased if diabetes is well-controlled—that is, if blood sugar is kept within or close to the normal range.

Retinopathy affects up to 80% of all diabetics who have had diabetes for 10 years or more; fortunately, many of these are in the early stages.^[2]. Most of these new cases could have been reduced in severity if there had been vigilant treatment and monitoring of the eyes.

Cross-section of a normal eye showing location of the retina. Source: NIH

Nonproliferative diabetic retinopathy showing macular edema, a cotton-wool spot below the optic disk, and a few hemorrhages and exudates. Source: PLoS Medicine

Types

There are four stages of diabetic retinopathy.

• Mild nonproliferative retinopathy. At this, the earliest stage, microaneurysms occur. They are small areas of balloon-like swelling in the retina's tiny blood vessels.
• Moderate nonproliferative retinopathy. As the disease progresses, some blood vessels that nourish the retina are blocked.
• Severe nonproliferative retinopathy. Many more blood vessels are blocked, depriving several areas of the retina with their blood supply. These areas of the retina begin sending signals to the body to grow new blood vessels for nourishment.
• Proliferative retinopathy. At this advanced stage, the signals sent by the retina for nourishment trigger the growth of new blood vessels. This condition is called proliferative retinopathy. These new blood vessels are abnormal and fragile. They grow along the retina and along the surface of the clear gel that fills the inside of the eye. By themselves, these blood vessels do not cause symptoms or vision loss. However, they have thin, fragile walls. If they leak blood, severe vision loss and even blindness can result.

A related disease called diabetic macular edema occurs when the blood vessels become more permeable, and hard deposits form on the retina. It often accompanies the above stages of retinopathy.

Signs and Symptoms

Often there are no symptoms in the early stages of the disease, nor is there any pain. Since the disease progresses over years or decades, the gradual changes may be so subtle that the patient delays seeking attention. Visual problems may include loss of the ability to see fine detail (visual acuity), loss of vision in particular areas (visual field defects), or blindness in one or both eyes.

Normal vision.

Same scene to someone with diabetic retinopathy. Source: NIH

Causes

As the name suggests, the disease is caused by long-standing, poorly-controlled diabetes. One theory of how high glucose levels cause new blood formation involves the accumulation of substances called advanced glycosylation endproducts (AGEs) in small capillaries, including those in the kidney and retina, of diabetics. AGEs are chemical substances that form in part because of high blood sugar. These AGEs can interact with a receptor, which results in oxidative stress generation and an inflammatory response, potentially playing a role in the development and progression of this disease.^[3]

How diabetic retinopathy causes vision loss

Blood vessels damaged from diabetic retinopathy can cause vision loss in two ways:

1. Fragile, abnormal blood vessels can develop and leak blood into the center of the eye, blurring vision. This is proliferative retinopathy and is the fourth and most advanced stage of the disease.
2. Fluid can leak into the center of the macula, the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the macula swell, blurring vision. This condition is called macular edema. It can occur at any stage of diabetic retinopathy, although it is more likely to occur as the disease progresses. About half of the people with proliferative retinopathy also have macular edema.

Diagnosis

Detection of diabetic retinopathy and macular edema requires examination of the retinas. The exam includes:

• Visual acuity test, in which the subject is asked to look at and identify letters or symbols at various distances
• Dilated exam, in which eye drops expand the pupils to allow a better look at the back of the eye, and a special lens is used to view the back of the eye.
• Tonometry. An instrument measures the pressure inside the eye. Numbing drops may be applied to the eye for this test.

The eye care professional checks the retina for early signs of the disease, including:

• Leaking blood vessels.
• Retinal swelling (macular edema).
• Pale, fatty deposits on the retina—signs of leaking blood vessels.
• Damaged nerve tissue.
• Any changes to the blood vessels.

If the eye care professional believes a patient needs treatment for macular edema, he or she may suggest a fluorescein angiogram. In this test, a special dye is injected into the patient's arm. Pictures are taken as the dye passes through the blood vessels in the retina. The test allows the eye care professional to identify any leaking blood vessels and recommend treatment.

Treatment

Early-stage lesions are not treated; rather, the doctor and patient work together to aggressively control the patient's blood sugar, in the hopes that disease progression can be slowed or stopped. Proliferative retinopathy is treated with laser surgery, in a procedure called scatter laser treatment. Scatter laser treatment helps to shrink the abnormal blood vessels and involves placing hundreds or thousands of microscopic laser burns in the affected areas of the retina, killing the proliferating cells in the targeted blood vessels. Because a high number of laser burns are necessary, two or more sessions usually are required to complete treatment. Peripheral vision, night vision, and color vision may be damaged or lost in order to save the most important central area of focus (the macula).

If there is active bleeding into the eye chamber containing the vitreous fluid, a surgical procedure called a vitrectomy may be necessary. In this procedure, blood is removed from the center of the eye and replaced with a similar clear fluid.

Prevention

Tight control of blood sugar^[4] and blood pressure reduces the chance of developing diabetic retinopathy.^[5] Regular eye exams can lessen the chance of missing opportunities to control the early stages of the disease.

Chances of Developing Diabetic retinopathy

Nearly all type 1 diabetics, and over 60% of type 2 diabetics, have some retinopathy after 20 years with diabetes.^[5]

Risk factors

Definite risk factors include:^[5]

• Duration of diabetes (the risk of retinopathy rises as time goes on)
• High blood sugars over an extended period (this can be measured with the hemoglobin A1C)
• High blood pressure
• High cholesterol
• Pregnancy
• Kidney disease

Possible risk factors include:^[5]

• Smoking
• Moderate consumption of alcohol
• Obesity
• Being physically inactive

Clinical Trials

Many studies that are currently recruiting new patients are listed at clinicaltrials.gov.

Research

Recent reports highlight important advances in detecting and treating diabetic retinopathy:

• Early detection efforts require screening asymptomatic diabetics, a time-consuming and expensive process. A recent report on automated screening of retinal photographs describes how a computer algorithm is used to decide whether a digital photograph of a retina shows evidence of retinopathy. Although the system is not yet ready for widespread use (there is still a high false positive rate), improvements should help efforts to prevent blindness in diabetics.^[6]

• Bevacizumab (Avastin} is a drug approved for use in cancer therapy that slows or prevents the formation of new blood vessels. Injection of this drug into the eye can temporarily slow this process in diabetic retinopathy. When used in conjunction with laser therapy, bevacizumab remarkably augmented the beneficial short-term response, but the effect was short-lived, as many of the eyes showed rapid recurrence.^[7]

• Other research efforts focus on such various agents as fibrates, octreotide, statins, cilostazol, and ruboxistaurin on the prevention and treatment of diabetic retinopathy.^[8]

Expected Outcome

People with proliferative retinopathy have less than a five percent chance of becoming blind within five years when they get timely and appropriate treatment.

Epidemiology

Diabetic retinopathy is the most common cause of blindness among working-aged people in developed countries.^[5] According to the American Diabetes Association, up to 21% of people with type 2 diabetes have retinopathy when they are first diagnosed with diabetes. ^[9]

References

1. ↑ WHO. Magnitude and Causes of visual impairment. World Health Organization. 2004 Nov. Full Text
2. ↑ Klein BE. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007 Jul-Aug;14(4):179-83. Abstract
3. ↑ Yamagishi S, Nakamura K, Matsui T, Noda Y, Imaizumi T. Receptor for advanced glycation end products (RAGE): a novel therapeutic target for diabetic vascular complication. Curr Pharm Des. 2008;14(5):487-95 Abstract
4. ↑ The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30;329(14):977-86. Abstract | Full Text
5. ↑ ^{5.0 5.1 5.2 5.3 5.4} Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007 Aug 22;298(8):902-16. Abstract | Full Text
6. ↑ Abràmoff MD, Niemeijer M, Suttorp-Schulten MS, Viergever MA, Russell SR, van Ginneken B. Evaluation of a system for automatic detection of diabetic retinopathy from color fundus photographs in a large population of patients with diabetes. Diabetes Care. 2008 Feb;31(2):193-8. Abstract | Full Text
7. ↑ Mirshahi A, Roohipoor R, Lashay A, Mohammadi SF, Abdoallahi A, Faghihi H. Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic retinopathy: a randomized double-masked clinical trial. Eur J Ophthalmol. 2008 Mar-Apr;18(2):263-9. Abstract
8. ↑ Bloomgarden ZT. Diabetic retinopathy and diabetic neuropathy. Diabetes Care. 2007 Mar;30(3):760-5. Full Text
9. ↑ American Diabetes Association: Diabetes and Retinopathy (Eye Complications)

External Links

• American Diabetes Association