A Look at Diabetic Retinopathy

FEBRUARY 01, 2006
Anna D. Garrett, PharmD, BCPS, CPP

Diabetic retinopathy (DR) is a leading cause of blindness and loss of vision in adults <60 years of age. Studies estimate that, among the 10.2 million adults with diabetes, 40.3% have diabetic retinopathy. Sight-threatening retinopathy is present in 8.2% of that group.1 Retinopathy is the most common microvascular complication of diabetes and results in blindness for >10,000 individuals per year.2 This complication has devastating effects from personal and societal perspectives. Patients with DR have significant qualitative and quantitative decreases in health-related quality of life.1 Treatment options are limited and marginally effective.

Evidence suggests that ocular damage from chronically elevated blood glucose may begin as early as 7 years prior to the clinical diagnosis of type 2 diabetes.3 Mechanisms leading to eye damage include polyol accumulation, which leads to high sorbitol concentrations in cells; formation of advanced glycation end products (AGEs); oxidative damage; and activation of protein kinase C (PKC). Activation of these pathways results in thickening of basement membranes, pericyte loss, and microaneurysm formation.

DR is a progressive condition that has 3 different stages: (1) no apparent DR; (2) nonproliferative DR; and (3) proliferative DR (PDR). Nonproliferative DR is characterized by dilation of veins in the eye, microaneurysms, retinal hemorrhages, and retinal edema hard exudates.4 In PDR, abnormal blood vessels begin to grow on the retina. These vessels can begin to leak, resulting in severe damage. At any stage in this progression, fluid can leak into the macula, causing blurred vision. This condition is known as diabetic macular edema (DME) and is one of the most common causes of vision loss in people with diabetes.

A number of techniques are available to make the diagnosis of DR, but ophthalmoscopy is used most commonly to monitor for DR. Regular dilated eye examinations can help prevent blindness and are a cost-effective approach to detecting DR. Annual examinations are recommended by the American Diabetes Association.5,6 The frequency of screening is controversial in low-risk patients, and some researchers have suggested that less frequent screening may be appropriate if a mechanism exists to prevent patient loss to follow-up.5

Currently, the most effective method of slowing progression of DR is glycemic control. The relationship between glucose control and retinopathy has been well-described in previous studies.7,8 Control of other comorbid conditions also has been shown to help delay progression of DR. Increased diastolic blood pressure has been associated with a higher incidence of macular edema, and intensive blood pressure control has been shown to delay progression of DR.9,10 Management of impaired renal function and serum lipid levels also has been shown to delay progression of DR.4

Limited treatment options are available for the treatment of sight-threatening DR. Laser photocoagulation has been shown to be effective in reducing the progression of DR, and vitrectomy can prevent severe vision loss in patients who are in advanced stages of DR. Both treatments may result in additional vision loss, however, and neither can reverse losses of vision that have already occurred.

A number of pharmacotherapeutic options have been or are currently under study for DR. Researchers are focusing on inhibiting each of the mechanisms of DR progression: accumulation of sorbitol, production of AGEs, increased oxidative stress, and activation of the PKC-βpathway. The most promising agents thus far appear to be those that block the PKC-β‚ pathway.4 Ruboxistaurin, an experimental inhibitor of the PKC pathway, has been shown to prevent and reverse the microvascular complications of diabetes, to prevent growth of new blood vessels on the retina, and to inhibit the effects of vascular endothelial growth factor (VEGF).

Medications that are currently available also have been studied.4 Aldose reductase inhibitors have been tested for their ability to reduce sorbitol accumulation, but they have not been proven to be of benefit. Antioxidants such as tocopherol have been studied, with conflicting results. High-dose aspirin (650 mg/day) may be beneficial as prophylaxis in the early stages of DME and DR, but the benefit does not appear to extend into later stages of the disease. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists decrease retinal VEGF expression. Further study is needed to determine whether the benefits of these medications are independent of their hypotensive properties.

Diabetic retinopathy is a potentially devastating microvascular complication of poorly controlled diabetes. Prevention of the disease by modifying underlying risk factors is the cornerstone of treatment. Options are limited and carry the risk of worsening vision. A number of pharmacologic treatments are currently under study and may prevent or reverse visual loss. Pharmacists can play a significant role in helping people to be better managers of their disease, thereby preventing long-term complications that can have a devastating effect on their lives.

Dr. Garrett is a clinical pharmacist practitioner at Cornerstone Health Care in High Point, NC.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.