Novel and Emerging Therapies
Vascular endothelial growth factor, also known as VEGF, is a protein thought to play a critical role in the neovascularization that causes the progression of retinopathy. Thus, compounds that inhibit the effects of VEGF, known as VEGF inhibitors, have been studied as a treatment for diabetic retinopathy and retinopathy of prematurity (a form of retinopathy that can occur in infants born prematurely). Because these drugs are designed to only work locally, they require injection into the vitreous to be effective (Arevalo 2013; Bandello 2012). Two VEGF inhibitors that have shown promising results in clinical trials are bevacizumab (Avastin®) and pegaptanib (Macugen®) (Tremolada 2007). VEGF inhibitors may be an effective adjunct to photocoagulation and other techniques, but more trials need to be done to determine if they are appropriate as an initial therapy for retinopathy (Fraser 2013; Arevalo 2013; Kumar, Gupta, Saxena 2012; Bandello 2012).
Protein Kinase C Inhibitors
Similar to VEGF, some of the vascular damage that occurs in the retina in diabetic retinopathy is caused by increased activity of a protein called protein kinase C. Inhibiting the activity of this enzyme via protein kinase C inhibitors may be effective for treating diabetic retinopathy. One of the first studied inhibitors, PKC412, improved visual acuity in patients with diabetic macular edema at an oral dose of 100 mg per day. Another orally administered compound, called ruboxistaurin, has been found to slow the development of vision loss in diabetics in clinical trials (Nawaz 2013; PKC-DRS Study Group 2005).
Many people with diabetes already take medications to lower their levels of cholesterol and other lipids. In addition to increasing the risk of coronary artery disease and stroke, elevated levels of lipids may also contribute to inflammation that can lead to progression of diabetic neuropathy. In clinical studies, one lipid-lowering medication – fenofibrate (Tricor®, Antara®, Lipofen®) – was found to reduce the risk of development and progression of diabetic retinopathy (Simo 2013). A study examining the effects of fenofibrate on complications of diabetes found that diabetics that took fenofibrate were less likely to require laser therapy to treat diabetic retinopathy (Nawaz 2013). Although the exact mechanism by which fenofibrate helps combat diabetic retinopathy is unclear, the drug is known to modulate several pathways involved in inflammation, angiogenesis, and cell survival, all of which may play a role in diabetic retinopathy (Noonan 2013). Combining fenofibrate with other lipid-lowering medications, such as simvastatin (Zocor®) may also be effective (Nawaz 2013). Because these lipid-lowering medications are already widely used, they represent an intriguing new strategy for treating retinopathy.
Photobiomodulation is a promising therapy for retinopathy of prematurity because it may help prevent damage from occurring in at-risk infants. In an animal model of retinopathy of prematurity, exposure of the subjects to light with a wavelength of 670 nm (ie, close to infrared light in wavelength) reduced signs of retinopathy. This treatment is based on the idea that certain wavelengths of light may help protect the eye from damage. Light at this wavelength reduces nerve cell death, decreases the formation of abnormal blood vessels and bleeding in the retina, and maintains healthy retinal blood vessels (Natoli 2013; Tang 2013). Experiments in rodent models have also found that photobiomodulation may be helpful for treating diabetic retinopathy (Tang 2013).