To Infinity Beyond in heenopathy

This is a good time to point out that there are a lot of other drugs in the pipeline—both for the eye and systemically—that may play a role in treating this disease. For instance, there are several sustained-release steroid implants being evaluated for use in diabetic retinopathy. It is likely that devices that slowly release other drugs, such as the anti-VEGF agents, will soon be developed.

There are also modified laser techniques that may result in significant changes in how diabetics are treated. Micropulse laser was mentioned in Chapter 3, but there is also a suggestion that standard laser can be used to indirectly control macular edema. Because VEGF comes from the ischemic peripheral retina, and because VEGF causes vascular leakage, it is thought that by doing mild panreti-nal photocoagulation in peripheral ischemic retina, one can help control leakage in the macula. As we shall see in subsequent chapters, one is always worried that panretinal treatment will exacerbate macular edema, so this thinking seems a bit counterintuitive. In fact, such an approach is not even new—it was suggested years ago, but now it can be viewed in the context of what we know about VEGF activity.4 This is not to say that everyone with macular edema needs a PRP—there are no studies yet that prove such an approach is valid. Rather, it is a reminder to keep an open mind and recognize that what we know "for sure" can easily change with time.

In terms of systemic therapy, the most obvious treatment is to simply address the patient's glucose control, as well as the other vascular risk factors discussed in Chapter 20. However, there are a host of other pathways that mediate the damage caused by diabetes, and a lot of research is directed toward finding drugs that can interfere with these pathways. For instance, protein kinase C subtype beta (PKC-beta) is an enzyme that is felt to contribute to diabetic microvascular damage when it is upregulated in hyperglycemic states. Ruboxistaurin is a PKC-beta inhibitor that was shown to have a mild effect on retinopathy. Unfortunately, the results have not been good enough to justify FDA approval, and further studies are under way. It does serve, however, as exciting proof that it is possible to prevent damage by means other than laser and drugs in the eye.

Note of Caution: Diabetes is the leading cause of blindness in patients under the age of 65, and any treatment shown to be effective—even a little—stands to make someone an awful lot of coin. It is hoped that everyone is driven largely by a desire to make the world a better place, but one person's major breakthrough may be another person's marginal improvement—and sometimes throwing a lot of money into the mix does not help to get the reality pinned down.

You may have noticed this if you were reading the eye literature a few years ago, when preliminary trials were being done on ruboxistaurin. There were drug company advertisements that simply talked about the PKC-beta enzyme alone, seemingly as a way to prepare everyone's mind for the drug's release. There were also announcements of its effectiveness in the ophthalmic community—yet the FDA did not approve it and requested further studies.

The point is that although it is hard enough to be the best clinician one can be, more and more one has to also be able to look critically at the data as new treatments come online. It gets even tougher when one has to balance the benefits of new treatments against the cost to society at large—and now this box is getting way off topic. Back to work.

Other pathways under examination include those involving growth hormone, insulin-like growth factor, metalloproteases, and various mediators of inflammation. There is also work being done with advanced glycation endproducts (AGEs). These are produced in higher than normal levels during episodes of hyperglycemia, and they seem to play a role in diabetic microvascular damage. There is even a receptor for these compounds (the very appropriate acronym for this receptor is "RAGE") and activation of this receptor appears to elicit oxidative stress and inflammation in various cells. Interfering with all of these mechanisms will likely give us better and better ways to prevent diabetic damage of all types.

It is inevitable that in the future we may have a totally different philosophy when it comes to treating diabetic reinopathy. We may be using very light lasers—or perhaps no lasers at all—in conjunction with local and/or systemic drugs. You should keep your eye on the literature and stay abreast of new developments— these are exciting times, and our present treatments will, hopefully, be relegated to museum displays that sit next to exhibits on bleeding and purging. However, there are still a lot of patients who can benefit from old-school treatments, so on to the next manifestation of diabetic retinopathy: proliferative disease.

References and Suggested Reading

1. Diabetic Retinopathy Clinical Research Network. A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Focal/Grid Photocoagulation for Diabetic Macular Edema. Ophthalmology. 2008 Sep;115(9):1447-9.

2. Gillies MC, Sutter FK, Simpson JM, Larsson J, Ali H, Zhu M. Intravit-real triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology 2006;113:1533-8.

3. Williams CP, Konstantopoulos A, Rowley SA, Luff AJ. Late intraocular pressure rise following intravitreal triamcinolone injection. Clin Experiment Ophthalmol 2007;35:385-6.

4. Gardner TW, Eller AW, Friberg TR. Reduction of severe macular edema in eyes with poor vision after panretinal photocoagulation for proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 1991;229:323-8.

Cunningham MA, Edelman JL, Kaushal S. Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol 2008;53:139-49.

Grover D, Li TJ, Chong CC. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev 2008:CD005656.

Furlani BA, Meyer CH, Rodrigues EB, et al. Emerging pharmacotherapies for diabetic macular edema. Expert Opin Emerg Drugs 2007;12:591-603.

Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA 2007;298:902-16.

Tremolada G, Lattanzio R, Mazzolari G, Zerbini G. The therapeutic potential of VEGF inhibition in diabetic microvascular complications. Am J Cardiovasc Drugs 2007;7:393-8.

Proliferative Diabetic Retinopathy and Other Things That Go Bump in the Night

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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