Diabetes and Eye Health - Diabetic Retinopathy

Diabetes mellitus (commonly referred to as diabetes) is a disease characterised by elevated blood sugar (glucose) levels. There are two forms of the disease – type 1 and type 2. Type 1 diabetes occurs when (for unknown reasons) the body's own immune system destroys the insulin-producing cells of the pancreas (called beta cells). Insulin is a hormone that regulates the level of glucose in the blood. When blood glucose levels are high, insulin stimulates body cells to absorb the glucose. Inside the cells, glucose is used as energy for cellular metabolism.

Type 1 diabetes usually occurs in childhood or adolescence (although it can start at any age), and people with this disease require treatment with insulin (usually administered by injection) for life. Approximately one in 10 people with the disease have type 1 diabetes.

Unlike people with type 1 diabetes, people with type 2 diabetes produce insulin; however, the insulin their pancreas secretes is either not enough or the body is unable to recognise the insulin and use it properly (insulin resistance). Type 2 diabetes is usually diagnosed in adulthood and managed with healthy lifestyle changes, typically in combination with tablets and/or insulin injections. Type 2 is the more common form of diabetes, affecting nine out of every 10 people with the disease.

Long-term complications of diabetes

Long-term complications of diabetes include disease of the large blood vessels (macrovascular disease) that leads to conditions such as coronary heart disease, stroke and peripheral vascular disease; and disease of the small blood vessels (microvascular disease) that can cause chronic kidney disease, nerve damage and retinopathy (loss of vision).

Diabetes is very common

Diabetes is the fastest growing chronic disease in Australia, and some experts refer to it as an epidemic.

Diabetes rates have tripled in the past two decades and are expected to triple again in the next two decades.

In 2011-12 there were about 1 million Australians with diabetes. Aboriginal and Torres Strait Islander people are 3-4 times more likely to have diabetes and have one of the highest prevalence rates of type 2 diabetes in the world. If diabetes continues to rise at the current rates, up to 3 million adult Australians will have diabetes by the year 2025. For type 2, this is likely driven by rising obesity, the ageing population, dietary changes, and sedentary lifestyles.

Visual Complications of Diabetes

Diabetes has the distinction of being the leading cause of blindness in adults. Diabetic retinopathy is a well known risk factor for visual impairment in diabetic patients. Perhaps less well appreciated is the fact that uncontrolled diabetes can adversely impact all ocular tissues.

Common Visual Complication of Diabetes

The most common and potentially most blinding of diabetic visual complications is diabetic retinopathy. Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness. Diabetic retinopathy is the result of damage to the tiny blood vessels that nourish the retina. They leak blood and other fluids that cause swelling of retinal tissue and clouding of vision. The condition usually affects both eyes.

Studies suggest that the most consistent risk factors for the development and severity of retinopathy are duration of diabetes, younger age at diagnosis, high glycosylated hemoglobin levels, and high systolic blood pressure. Cigarette smoking is a well known risk factor for the development of vascular disease. Smoking has been shown to increase risk of developing diabetes as well as diabetic retinopathy.

Symptoms of Diabetic Retinopathy

In the initial stages of diabetic retinopathy, patients are generally asymptomatic; in the more advanced stages of the disease, however, patients may experience symptoms that include floaters, blurred vision, distortion, and progressive visual acuity loss.

How Does Diabetic Retinopathy Cause Loss of Vision?

Diabetic retinopathy is a general term for all disorders of the retina caused by diabetes. Diabetic retinopathy can be divided into two stages: an early stage, known as non-proliferative diabetic retinopathy, and a later stage referred to as proliferative diabetic retinopathy.

In people with diabetes, changes in the walls of the small blood vessels in the retina are caused by blood sugar abnormalities. These small blood vessels may begin to swell or "balloon," forming what are called microaneurysms. Microaneurysms are the earliest sign of non-proliferative retinopathy.

These swollen blood vessels are fragile and may leak fluid or blood. Fluid that leaks from the microaneurysms is termed 'oedema.' If the fluid leakage affects the macula (the central part of the retina that is responsible for fine detail vision), vision loss may be mild to severe. Diabetic macular oedema is the leading cause of vision loss associated with diabetes, causing visual impairment at twice the rate of that caused by proliferative diabetic retinopathy.

Blood may also leak from these vessels forming what are called 'dot and blot haemorrhages.' As the disease progresses, proteins and lipids (fats) leak from the blood vessels forming what are known as 'exudates.'   The stages of non-proliferative retinopathy are outlined below.

Nonproliferative diabetic retinopathy stages 

• Mild: Indicated by the presence of at least 1 microaneurysm
• Moderate: Includes the presence of hemorrhages, microaneurysms, and hard exudates
• Severe (4-2-1): Characterized by hemorrhages and microaneurysms in 4 quadrants, with venous beading in at least 2 quadrants and intraretinal microvascular abnormalities in at least 1 quadrant

As the condition progresses, the smaller vessels may close and the larger retinal vessels may begin to dilate and become irregular in diameter. This signals the onset of the more advanced stage of diabetic retinopathy called proliferative diabetic retinopathy. Proliferative diabetic retinopathy is characterised by the growth (proliferation) of new, abnormal blood vessels on the retinal surface. These new blood vessels may bleed into the jelly-like substance in front of the retina (vitreous haemorrhage), and they may be associated with the formation of fibrous scar tissue that can pull on the retina, causing it to detach from the back of the eye (tractional retinal detachment).

If diabetic retinopathy progresses, blood vessels in the retina are so damaged that they close off. These blockages, when affecting a significant part of the retina, can result in areas of the retina becoming starved of oxygen. This is called ischaemia. This stimulates the eye to grow new vessels, a process called neo-vascularisation. This is nature’s way of trying to repair the damage by growing a new blood supply to the oxygen starved area of the retina.

Unfortunately, these new blood vessels are weak, and grow in the wrong place – on the surface of the retina and in the vitreous gel. As a result, these blood vessels can bleed very easily resulting in large haemorrhages over the surface of the retina or into the vitreous gel. These types of haemorrhages can totally obscure the vision in the affected eye as light is blocked by the blood in the vitreous gel. For many people, with time, the blood can be reabsorbed and vision can improve. But for others, these haemorrhages continue to occur and the blood may not be fully reabsorbed leading to permanent loss of sight.

Extensive haemorrhages can lead to the formation of scar tissue which pulls and distorts the retina. This type of advanced diabetic eye disease can result in the retina becoming detached with the risk of serious sight loss. The new blood vessels can also cause scar tissue to grow. After the scar tissue shrinks, it can distort the retina or pull it out of place, a condition called retinal detachment. The characteristics of proliferative diabetic retinopathy are outlined below.

Proliferative diabetic retinopathy 

• Neovascularisation: Hallmark of PDR
• Preretinal hemorrhages: Appear as pockets of blood within the potential space between the retina and the posterior hyaloid face; as blood pools within this space, the hemorrhages may appear boat shaped
• Hemorrhage into the vitreous: May appear as a diffuse haze or as clumps of blood clots within the gel
• Fibrovascular tissue proliferation: Usually seen associated with the neovascular complex; may appear avascular when the vessels have already regressed
• Traction retinal detachments: Usually appear tented up, immobile, and concave
• Macular edema

How Is Diabetic Retinopathy Treated?

Broadly speaking, there are three types of treatment for diabetic retinopathy. These include laser therapy, intravitreal injections (direct injection of medication into the vitreous, the jelly-like substance in the eye), and in more severe cases, surgical vitrectomy where the vitreous is removed from the eye.

What Is Laser Therapy?

Laser therapy, also known as laser photocoagulation is a surgical procedure which utilises a powerful, very precisely focused beam of light (laser) to create microscopic thermal burns and treat abnormalities of the macula and/or retina. There are three general types of laser photocoagulation:

• Macular laser treatment
• Panretinal photocoagulation/scatter photocoagulation
• Laser photocoagulation to treat retinal tears

All three forms of laser photo­coagulation are routinely performed in the office as outpatient procedures.

Treatment for Non-proliferative Diabetic Retinopathy

With the exception of macular oedema, nonproliferative diabetic retinopathy requires no invasive treatment. According to The Diabetes Control and Complications Trial, tight glucose control and maintaining the hemoglobin A1c (HbA1c) level in the 6-7% range can substantially reduce the progression of diabetic retinopathy.

Maintaining a healthful lifestyle with regular exercise is important, especially for individuals with diabetes.

Exercise can assist in maintaining optimal weight and with peripheral glucose absorption.

This can help with improved diabetes control, which, in turn, can help reduce the complications of diabetes and diabetic retinopathy.

Laser treatment is, however, indicated in the treatment of clinically significant macular oedema. If the oedema is due to leakage of specific microaneurysms, the leaking vessels are treated directly with focal laser photocoagulation. In cases where the foci of leakage are nonspecific, a grid pattern of laser burns is applied. The Early Treatment for Diabetic Retinopathy Study found that laser surgery for macular oedema reduces the incidence of moderate visual loss from 30% to 15% over a 3-year period.

Several medications are used in an off-label manner in the treatment of diabetic macular oedema. At present, these medications are administered into the eye by intravitreal injection (direct injection of medication into the vitreous, the jelly-like substance within the eye). Intravitreal triamcinolone (Kenalog) is being used in the treatment of diabetic macular oedema. A recent clinical trial sponsored by the Diabetic Retinopathy Clinical Research Network (DRCR.net) demonstrated that although some reduction in macular oedema occurred after intravitreal triamcinolone, this effect was not as robust as that achieved with focal laser treatment at the primary endpoint of 2 years. In addition, intravitreal triamcinolone (a corticosteroid) can produce adverse side effects associated with steroid use such as increased intraocular pressure and cataracts.

Other medications being used in the treatment of macular oedema include intravitreal bevacizumab (Avastin) and ranibizumab (Lucentis). Bevacizumab is a recombinant humanised monoclonal antibody that blocks the growth of blood vessels by inhibiting vascular endothelial growth factor A (VEGF-A). Ranibizumab is a monoclonal antibody fragment that also blocks the growth of blood vessels. Combinations of some of these medications with focal laser treatment have been investigated in the DRCR.net clinical trials and have proven efficacy.

Treatment for Proliferative Diabetic Retinopathy?

Proliferative retinopathy is treated with laser surgery. Panretinal photocoagulation (also known as scatter photocoagulation) is the preferred form of treatment of proliferative diabetic retinopathy. Panretinal laser involves the application of typically between 1500 and 2000 laser spots to the majority of the retina, sparing the macula – the region serving central vision. The Diabetic Retinopathy Study has found that adequate panretinal photocoagulation reduces the risk of severe visual loss (< 5/200) by more than 50%.

The exact mechanism by which laser therapy works is not entirely understood. One theory is that by destroying the hypoxic retina, the production of vasoproliferative factors such as VEGF is reduced which then decreases the rate of neovascularisation. Another theory is that photocoagulation allows increased diffusion of oxygen from the choroid to the retinal circulation. The enhanced oxygen delivery also down-regulates vasoproliferative factor production and subsequent neovascularization.

Surgery may be required to treat advanced diabetic retinopathy. The most common reasons for surgery are for the treatment of bleeding into the vitreous (jelly-like substance within the eye) of the eye that obscures vision, or pulling on the retina exerted by fibrous scar tissue that can cause the retina to detach (tractional retinal detachment). In these cases, a surgical procedure known as vitrectomy is performed, where the vitreous is removed and replaced with a saline solution, gas or silicone oil. According to The Diabetic Retinopathy Vitrectomy Study, vitrectomy is advisable for eyes with vitreous hemorrhage that fails to resolve spontaneously within 6 months.

Can Diabetic Retinopathy Be Prevented?

The Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study were large randomised clinical trials that demonstrated the importance of tight glucose control with respect to reducing the incidence and progression of diabetes complications, including diabetic retinopathy for both type I and type II diabetes.

All individuals with diabetes should be aware of the importance of regular dilated retinal examinations. Early diagnosis and treatment of diabetic retinopathy can help prevent blindness in more than 90% of cases. In spite of treatment, however, individuals can sometimes still lose vision.

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