Management of Diabetic Retinopathy in the 21st Century

Drug treatment research hoped to decrease need for laser surgery.

By A.Paul Chous, MA, OD, FAAO

For most patients with diabetic retinopathy, the treatment of choice is improved metabolic control. This is to say that improving blood glucose levels (with an HbA1c goal as close to normal as possible, but less than 6.5%), blood pressure levels (with a goal of less than 130/80), and blood lipid levels (with a goal of LDL cholesterol less than 100, HDL cholesterol more than 50 and triglycerides less than 150) greatly reduces the risk of diabetic retinopathy getting worse. In fact, improved metabolic control is recommended for every patient having diabetes, both those with and without retinopathy, because it reduces the risk of virtually all diabetes complications.

However, when diabetic retinopathy progresses to a level that threatens vision, more aggressive therapy is recommended. In fact, laser photocoagulation (light energy of a particular wavelength used to destroy specific areas of the eye's light-sensitive retina) is the "gold standard" treatment for the most serious stages of diabetic retinopathy – proliferative retinopathy and significant diabetic macular edema – as laser has been shown to reduce the risk of both moderate and severe permanent vision loss by 50-75%.

Laser therapy for treatment of diabetic retinopathy is not without its drawbacks, though, because it is destructive by design; some retinal tissue is intentionally destroyed (sacrificed) in order to preserve the function of other, more visually important areas of retinal tissue, thereby lowering the chance of more serious vision loss and blindness. As a result, patients very often experience a loss of peripheral (side) vision, abnormal blind spots, and reduced ability to see at night or in dimly lit environments. Occasionally, laser photocoagulation itself results in scar tissue on the retinal surface that can distort or otherwise impair vision, or abnormal blood vessels and bleeding beneath the retina that severely affects vision - and sometimes, laser treatment simply doesn't work to stop progression of retinopathy. It is for all these reasons that scientists have been trying to develop drug therapies to replace or at least minimize the need for laser treatment.

In fact, a whole host of novel pharmaceutical and neutriceutical agents have been developed and, sometimes, tested for treating retinopathy. Unfortunately, most of these therapies have either not worked, caused serious medical side effects, and/or have not been tested in large clinical trials rigorously designed to scientifically determine their value. This is beginning to change, however, as scientists have uncovered the biochemical processes that lead to the development and progression of diabetic retinopathy.

One type of drug designed to interrupt the chemical signals causing growth of abnormal retinal blood vessels (as happens in proliferative diabetic retinopathy and several other serious eye diseases) are the VEGF inhibitors. VEGF is an acronym for vascular endothelial growth factor, a biochemical released by damaged blood vessels in the eye when they are exposed to high blood glucose levels for an extended period of time. MacugenTM, LucentisTM, and AvastinTM are three VEGF inhibitors that are being tested for treating proliferative diabetic retinopathy. SandostatinTM is another type of drug that may prove beneficial in the treatment of proliferative retinopathy; it is currently used to treat certain endocrine tumors because it suppresses blood vessel growth that promotes their development.

Protein kinase C (PKC) is a family of proteins implicated in the development of diabetic macular edema, and PKC inhibitors may help forestall this disease, the most common cause of significant vision loss from diabetes. ArxxantTM is the first FDA-approved drug to prevent vision loss from macular edema in patients with moderate to severe non-proliferative diabetic retinopathy. Benfotiamine is a non-prescription, fat-soluble form of Vitamin B1 (thiamine) that has been shown to block production of PKC and other biochemicals known to lead to diabetes complications; it totally prevented diabetic retinopathy in laboratory animals and is currently in human trials.

As for currently used medicines, there are several that may protect patients from diabetic retinopathy. The insulin sensitizing agents, rosiglitazone (AvandiaTM) and pioglitazone (ActosTM) have been implicated in the rare development of diabetic macular edema, especially in patients who experience peripheral fluid edema (swelling) and weight gain. Perhaps much more importantly, recent evidence presented at the Association for Research in Vision and Ophthalmology meeting indicates that patients treated with AvandiaTM were much less likely to develop serious diabetic retinopathy and no more likely to develop macular edema than were other patients with similar HbA1c values, blood pressure and duration of diabetes; it is thought that drugs like AvandiaTM and ActosTM may block the action of VEGF. There is also some evidence that cholesterol-lowering "statin" drugs and certain high blood pressure medicines (ACE inhibitors and ARBs) may lower the risk of diabetic retinopathy. Finally, cortisone (steroid) medicines are now widely used in combating retinopathy, often in combination with laser treatment, as they have been shown to improve or stabilize vision in certain circumstances (primarily severe macular edema).
Although new drugs for diabetic retinopathy hold great promise, it must be remembered that excellent metabolic control and timely laser treatment are still the current "gold standards" for managing this serious eye disease, and for good reason: they prevent blindness in the overwhelming majority of patients. However, treatment and prevention of diabetic retinopathy in the 21st Century will almost certainly involve a combination of therapies that battle the disease from different directions. Hopefully, this strategy will prevent any diabetes-related vision loss as well as side-effects caused by treatment itself.


Sources
The PKC-DRS Study Group. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes. 2005 Jul;54(7):2188-97.
Adamis AP, Altaweel M, Bressler NM, Cunningham ET Jr, Davis MD, Goldbaum M, Gonzales C, Guyer DR, Barrett K, Patel M; Macugen Diabetic Retinopathy Study Group. Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology. 2006 Jan;113(1):23-8.

 

 

Spaide RF, Fisher YL. Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage. Retina. 2006 Mar;26(3):275-8

Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):352-4.

Hammes H, Brownlee M et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents diabetic retinopathy. Nature: Medicine 2003; 9: 294-9.
Grant MB, Caballero S Jr. The potential role of octreotide in the treatment of diabetic retinopathy. Treat Endocrinol. 2005;4(4):199-20.
Ryan EH Jr, Han DP, Ramsay RC, Cantrill HL, Bennett SR, Dev S, Williams DF. Diabetic macular edema associated with glitazone use. Retina. 2006 May/June;26(5):562-570.
Rosiglitazone May Delay Progression to Proliferative Diabetic Retinopathy. Abstract 2333, Association for Research in Vision and Ophthalmology annual meeting, Fort Lauderdale, FL, May 2, 2006.

For more information on diabetic eye disease, consult Dr. Chous' book Diabetic Eye Disease: Lessons From a Diabetic Eye Doctor, Fairwood Press, Seattle, 2003.

Read more about Dr. Chous here.

Visit Dr. Chous' website here.


NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.

Last Modified Date: June 28, 2013

All content on dLife.com is created and reviewed in compliance with our editorial policy.

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