21st Century Treatment of Diabetic Retinopathy

Five-Year View

At present there is no treatment that will prevent the development of DR or its progression to sight-threatening lesions. Scientific research worldwide continues to improve our understanding of the pathogenesis of DR from which new effective therapies will emerge. Recent use of powerful mass spectroscopy-based proteomics technique has also helped in identifying the role of extracellular carbonic anhydrase (CA)-I in diabetic retinopathy.^[62] In addition to the well-documented vascular changes, recent studies are also suggesting the role of neuronal and glial dysfunction in the pathogenesis of DR.^[63]

Naturally, the treatment of sight-threatening lesions appears to be most urgent and laser photocoagulation treatment, although destructive, is, on the whole, very effective and will be the mainstay of treatment for the immediate future. Lasers are being improved, for example, the use of subthreshold diode micropulse (SDM) effectively treats severe NPDR and PDR without causing laser-induced retinal damage and the complications associated with conventional photocoagulation.^[64] Unfortunately there are no large-scale studies with long enough follow-up to determine their effectiveness. For end-stage retinopathy, vitrectomy will also remain the only approach.

A number of strategies are currently being tested to combat sight-threatening DR and prevent the use of a laser. So far, ruboxistaurin mesylate (Arxxant), a specific inhibitor of the diabetes-sensitive PKCβ1/2, has been tested clinically, with some encouraging results, for the treatment of sight-threatening DR. Although ruboxistaurin failed to prevent progression to PDR, it did reduce the risk of moderate vision loss caused by DME. Despite this improvement in visual loss, the FDA has requested additional data before any approval for medication use of ruboxistaurin. If approval is granted in the future, ruboxistaurin has the potential to be the first oral therapy to specifically reduce the risk of vision loss caused by DR. As patients have no symptoms at that stage, there will be a problem in convincing them to take the drugs, which will have to be administered orally and must have minimal side effects.

Along with the developments in the use of ACE inhibitors, GH inhibitors, corticosteroids (triamcinolone acetonide, fluocinolone acetonide and dexamethasone), intravitreal injections of anti-VEGF agents (pegaptanib, bevacizumab and ranibizumab) could be effective as individual and/or combination medication to combat sight-threatening DR and possibly replace the use of lasers. However, further studies are still needed to assess the safety of repeated intravitreal injections (a possible burden to the patient), needed to achieve optimum benefit and to question the effect of discontinuing the injection on the disease progression and visual loss.

Hyaluronidase (Vitrase, ISTA Pharmaceuticals), plasmin and microplasmin are enzymes that liquefies the vitreous, are also being developed for the clearance of vitreous hemorrhage and treatment of DR

The incidence and progression of retinopathy can be significantly reduced by strict control of glucose (hypoglycemic treatment) and blood pressure (antihypertensive treatment). New drugs are being developed to control blood glucose levels. For example, exenatide, an incretin mimetic agent, improves glucose control by mimicking the effects of glucagon-like peptide-1, a natural mammalian incretin hormone secreted during food intake. Exenatide has been approved by the FDA for the treatment of Type 2 diabetes in conjunction with metformin and/or sulfonylurea. New developments in this area, including new insulin and inhaled insulin, will continue to benefit patients with diabetes.

New medications, individually or more likely in combination, will be administered early in the disease and will prevent the progression and possibly even the development of DR. They are likely to affect the basic pathological processes and will include powerful anti-inflammatory drugs. It is possible that more than one pathway will have to be blocked but if the initial abnormality, occlusion of small vessels, can be prevented severe DR will be avoided.

Much has been achieved in the last 30 years, but the best is yet to come.

Expert Rev Endocrinol Metab. 2007;2(5):623-631. © 2007 Future Drugs Ltd.

Cite this: 21st Century Treatment of Diabetic Retinopathy - Medscape - Sep 01, 2007.