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Treatments for use as first-line therapy for DME

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In this issue we will explore the controversial subject of which treatment to use as the first-line therapy for diabetic macular edema (DME). Although laser treatment has traditionally been the standard treatment for DME, there may be circumstances in which either pharmacotherapy with intravitreal triamcinolone (IVTA), bevacizumab (Avastin, Genentech), pegaptanib sodium (Macugen, (OSI) Eyetech, Pfizer), or vitrectomy surgery may be beneficial. While we are not recommending any particular treatment for your patients, the column will be a nice exercise in exploring pro and con aspects of treatment decisions that we face daily.  


1. Laser as first-line treatment for DME

2. Pharmacotherapy (IVTA/Avastin) as first-line treatment for DME

3. Vitrectomy surgery as first-line treatment for DME

Laser as First-Line Treatment for DME


Einar Stefánsson MD, PhD: There is a metabolic imbalance, and/or hypoxia, in DME and this leads to production of permeability factors (VEGF, etc.) and increased hydrostatic pressure in microvasculature (Starling's law). We have means to permanently correct the metabolic imbalance through laser destruction of photoreceptors. Antigrowth factor drugs are a temporary method to block growth factors, while they do not influence the underlying metabolic imbalance. Steroids are also a temporary block of the permeability increase, and the underlying metabolic defect persists and takes over again when the drug clears.


Maurice B. Landers, III, MD: Because the United States is not a single, homogenous population, many patients will continue to present initially with advanced macular edema; extensive laser treatment initially in these patients may produce extensive scarring. New modalities (intravitreal kenalog and intravitreal anti-VEGF drugs) appear to significantly ameliorate the diabetic CSME initially. Once that is accomplished, it now may well be the most appropriate time to apply relatively light laser treatment, to achieve its beneficial effects with minimal attendant damage to the retina and RPE.

Pharmacotherapy (IVTA/AVASTIN) as First-Line Treatment for DME


Michael W. Stewart, MD:

1. Intravitreal pharmacotherapy avoids the permanent scarring of the retina and RPE that would be caused by laser photocoagulation.

2. The medications offer a reasonable chance of improving — and not just maintaining — visual acuity.

3. By binding VEGF or decreasing its production, pharmacotherapy may decrease or prevent diabetes-related neovascularization of the disc, retina, and iris.

4. As reported in individual case discussions, VEGF-binding may improve capillary perfusion and, thereby, possibly reverse ischemia-driven macular edema.

5. Intravitreal injections do not require expensive equipment (ie, laser).

6. The costs for individual injections are quite low (triamcinolone and bevacizumab but not pegaptanib).


Maurice G. Syrquin, MD: I remember treating patients for macular edema secondary to CRVO using focal laser while a fellow at the Jules Stein Eye Institute. This treatment was thought to be of value prior to the release of the CRVO study. Without a well-constructed prospective randomized clinical trial, I may have been performing an unnecessary procedure on my patients, but we now know better. Similarly, by treating our patients with DME using pharmacologic agents without a randomized clinical trial to support our treatment, we may again be introducing our personal bias. Our gold standard should be evidence-based medicine.

Vitrectomy Surgery as First-Line Treatment for DME


David J. Browning, MD: It is reasonable to consider an intervention that includes vitrectomy as a primary intervention for severe cases of DME. The definition of severe will mean different things to different people. In my mind, this means that best-corrected visual acuity is 20/60 or worse and central subfield macular thickness is over 450 μm. Vitrectomy by itself as an intervention is difficult to defend, but as the foundation for a combination primary intervention that might also include internal limiting membrane (ILM) stripping, focal laser, panretinal laser (should midperipheral ischemia exist by fluorescein angiography), and intravitreal pharmacologic therapy, the idea has merit, for the following reasons:

1. Vitrectomy raises preretinal oxygen concentration, which may downregulate VEGF in hypoxic retina.

2. Vitrectomy decompartmentalizes potential pockets of increased preretinal growth factors and relieves diffusion barriers to the outmigration of these factors from the retina.

3. Vitrectomy releases traction, which may decrease intraretinal vascular hyperpermeability.

4. Vitrectomy changes the state of the eye, like photocoagulation, and unlike a pharmacologic injection. Case series suggest that the effects of vitrectomy to thin the edematous macula do not wane, at least time courses up to a year.

5. The effect size of vitrectomy is larger than that of focal laser as a fraction of baseline thickening in case series, and is a more appropriate match for markedly edematous maculas.


David S. Boyer, MD:

Without prospective randomized clinical trials, vitrectomy surgery for DME should only be considered for patients who have a taut posterior hyaloid and have not responded to less-invasive treatments. The ETDRS study was a well-done multicentered clinical trial that has given us guidelines to treating patients with DME. The is exploring, in well-controlled prospective clinical trials, the role of vitrectomy, anti-VEGF drugs, and steroids to treat patients who have DME; many who have failed laser treatment. Despite the advances in vitrectomy surgery, there are still significant risks involved with vitrectomy surgery for taut hyaloid in patients with diabetes. These prospective trials will determine the role of surgery in the future.

Abdhish R. Bhavsar, MD, is an attending retina surgeon at the Phillips Eye Institute, director of clinical research at the Retina Center, P.A., in Minneapolis, Minn, and adjunct assistant professor at the University of Minnesota. He also serves as state chair of the Minnesota Diabetes Eye Exam Initiative. E-mail him about Face Off at