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Proliferative Diabetic Retinopathy

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Diabetes often leads to damage of the blood vessels, especially if the blood sugar levels are not well controlled. Swelling, leaking or blockage of the blood vessels in the eye causes a serious condition, proliferative diabetic retinopathy.

The retina is a light-sensitive tissue lining the back of the eye. In your eye, the light rays that pass through the pupil, are focused in the lens, and penetrate to the retina, where they are transformed into signals that are transmitted by the optic nerve to the brain and interpreted as images. Therefore, it is as essential for your vision, as a processor for a computer. Your retina has multiple delicate blood vessels that deliver oxygen and nutrients to sustain its function.
Elevated blood sugar leads to thinning of the blood vessel walls and clumping of the red blood cells. These two processes lead to blood leakage and vessel obstruction. Retina becomes swollen when the blood leaks from the vessels damaged by diabetes. When the blood vessels get blocked, retinal cells become deprived of oxygen and nourishment in the area of the blood vessel obstruction. A small specialized area in the center of the retina, called macula, is especially sensitive to the consequences of the blood vessel damage. Macula is essential for clearly seeing the details of the objects located in front of you. If macula becomes swollen (a condition called macular edema), it causes blurry vision, and an impairment of the ability to recognize faces or read.

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proliferative diabetic retinopathy
The National Eye Institute (NEI) defines four distinct stages, through which the diabetic retinopathy may progress. These are mild, moderate, and severe non-proliferative diabetic retinopathy, and proliferative retinopathy. The first three diabetic retinopathy stages differ by the number of the swollen, distorted, and blocked blood vessels in the retina. Macular edema may develop even at the second stage of the disease progression. During the third stage, oxygen and nutrient deprivation of the retina caused by the vessel blockage triggers secretion of a special molecule that stimulates the new blood vessel growth. This molecule is called vascular endothelial growth factor, VEGF in short. VEGF secretion promotes diabetic retinopathy to its most advanced, proliferative stage. It is characterized by the growth of the new blood vessels in the retina, a process called neovascularization.
Proliferative retinopathy is especially harmful for vision. The newly formed blood vessels are extra fragile, and the blood leaking from them is spilled from the retina to vitreous gel, a jelly-like transparent substance inside the eye, through which the light passes on its way from the lens to the retina. The blood accumulation in vitreous gel blocks vision partially, causing appearance of black "floaters" in your field of vision, or completely, causing blindness. Neovascularization of the retina can scar this delicate tissue, causing retinal detachment from the back of the eye. Detached retina cannot convert the light rays to nerve signals, leading to partial or complete blindness.

In summary, the diabetic retinopathy may cause macular edema even at the initial stages of development. In its advanced, proliferative stage, it causes the blood accumulation in the vitreous (vitreous hemorrhage), and retinal scarring and detachment. The retinopathy usually develops simultaneously in both eyes, causing the following symptoms:
• Blurry vision, or changes from clear to blurry vision and back
• Floaters and dark or black spots appearing in the field of vision
• Poor night vision
• Changes in color perception, with colors appearing faded or washed off

Diabetic retinopathy is detected during a comprehensive eye exam. It may include the following tests, exams and procedures:
• Visual activity test. The eye chart reading measures your ability to see at various distances.
• Tonometry. A test that measures pressure inside the eye.
• Funduscopy. Its a fancy name of an eye exam performed using a magnifying glass. The drops placed on the eye surface widen (dilate) the pupil, so the physician can visually examine the "eyegrounds", including the retina, retinal blood vessels, and the optic nerve. Fundoscopy detects changes in blood vessels (aneurisms), leaky blood vessels and fatty deposits, macular edema, and changes in the lens and abnormalities in the optic nerve.
• Optical coherence tomography (OCT). This test resembles an ultrasound exam but uses light instead of sound waves. OCT provides detailed images of eye tissues and complements the visual inspection of the retina.
• Fluorescein angiogram. In this procedure a fluorescent dye is injected into an arm vein. When the dye reaches the eye, multiple detailed pictures of the retinal blood vessels can be taken, revealing blood leaks and blood vessel changes that otherwise escaped detection.
The last two procedures are used if macular edema or progressive diabetic retinopathy are suspected.

Many treatment methods for the diabetic retinopathy are focused on repairing or removing the damaged blood vessels and restoring the blood flow in the retina. For the best effect, two or more therapies may be combined

. VEGF, a vascular endothelial growth factor, is a key molecule that induces neovascularization, promoting advancement of diabetic retinopathy to its fourth stage, the proliferative retinopathy. Drugs that counteract VEGF action are injected in the vitreous gel of the eye every month for half a year. After that the frequency of the injections is gradually decreased, and the treatment is completed within five years. Anti-VEGF drugs include Avastin (bevacizumab), Lucentis (ranibizumab), and Eylea (aflibercept). Avastin is approved by the U.S. Food and Drug Administration (FDA) as an anti-cancer medication, but it is also used to treat eye conditions, including macular edema. Lucentis and Eylea are approved for treating macular edema and diabetic retinopathy. Anti-VEGF therapy is showing a great promise for treatment of macular edema and proliferative diabetic retinopathy.

proliferative diabetic retinopathy
. This treatment is also called scatter laser surgery, or photocoagulation. It involves making several thousand microscopic laser burns to shrink the abnormal blood vessels. The burns are aimed in the areas away from macula to preserve the central vision. The side effects of panretinal laser surgery include some loss of peripheral vision, and defects in night and color vision, caused by laser-induce damage of parts of the retina.
Vitrectomy. If proliferative retinopathy results in accumulation of blood in the center of the eye, which blocks vision, the vitreous gel is surgically removed. This procedure includes removing the vitreous gel by suction and replacing it with sterile saline solution to preserve the pressure in the eye and maintain the eye shape. Vitrectomy can be done under local or general anesthesia; it often requires a hospital stay, and recovery takes several weeks. When both eyes require the surgery, the second vitrectomy is performed after the first eye is completely recovered.
If proliferative diabetic retinopathy is combined with macular edema, specific treatments for the latter can be combined with the panretinal laser surgery and anti-VEGF therapy.
Injection or implantation of corticosteroids. Corticosteroids have anti-angiogenic, anti-permeability, and anti-fibrotic properties. It means that they prevent the new blood vessel growth, decrease leakage of fluid into the retina, and prevent retinal scarring. Injections of steroids, commonly triamcinolone, into the vitreous gel are performed in the same way as in the anti-VEGF therapy. Implants are also placed in the vitreous and deliver sustained amount of medication for a defined time. Some implants are designed for a short-term treatment, like Ozurdex (dexamethasone). Iluvien (fluocinolone acetonide) is used for longer treatment. The flexibility of choice of the steroid treatment regimen is essential, steroids are known to increase the pressure in the eye, promoting glaucoma development. Glaucoma is more common in diabetics than in general population, therefore consider discussing the risks and benefits of the steroid treatment with your physician.
Focal/Grid macular laser surgery. Opposite to the panretinal surgery, this treatment specifically targets the macula. 10-100 laser burns are inflicted to remove and seal the damage blood vessels to prevent blood leakage and minimize macular swelling. This treatment can be combined with anti-VEGF therapy or used as a second line of defense if the anti-VEGF therapy turned out ineffective.

Although diabetic retinopathy is the most common and the most serious eye disease related to diabetes, other complications, such as glaucoma and cataracts, are known to affect vision in diabetic patients.
Glaucoma is a condition when the optic nerve is damaged and fails to transmit signals from the retina to the brain. In most cases, glaucoma is caused by the increased pressure in the eye. In diabetes, the growth of the new blood vessels in the iris can block the fluid flow in the eye. The pressure inside the eye increases, and a condition called a neovascular glaucoma may develop. It is also known that people with diabetes develop a more common type of glaucoma, an open-angle glaucoma, twice as frequently as non-diabetics. However, the opposite is also true: glaucoma patients have an increased chance of developing diabetes. Therefore, it is not clear if a high blood sugar causes the open-angle glaucoma, or the two diseases share some common risk factors.
Cataracts is a common cause of blindness caused by clouding of the lens. The incidence of cataracts in diabetics is twice as high as in non-diabetics. It might be caused by a chronic lens swelling caused by the constantly elevated blood sugar. Also, sudden sharp changes of the blood sugar concentration may cause distortion of the lens shape.

Diabetes contributes to development of serious eye diseases, such as proliferative diabetic retinopathy, macular edema, glaucoma and cataracts. Your best way to prevent the diabetes-related blindness is to keep your blood sugar in check by combination of diet, exercise, and medications. The incidence of diabetic retinopathy development in those diabetic patients who maintain their hemoglobin A1c levels below 7.0, is the same as in non-diabetics.
Diseases of the eye are easier to treat when they are detected at early stages. Therefore, all diabetic patients should get a comprehensive eye exam at least once a year. Regular ophthalmologist visits ensure the timely detection and treatment of the diabetic retinopathy, glaucoma and cataracts.
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Keith E. Barker

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