Sorting Through DME Treatment Options

Laser-based therapy, in various iterations, has long been a mainstay of managing diabetic retinopathy.

By David D. Gossage, DO

Diabetes is a devastating disease that affects millions of people in the United States that are still of working age. It is the leading cause of new cases of blindness among adults younger than 74 years, and 11.3% of all individuals aged 20 years or older have diabetes.1 Extensive research and development has been invested in looking for ways to slow down the progression of diabetic retinopathy, and there are several interesting options for treating patients.

One of the first major double-blind studies of diabetes in ophthalmology, the Early Treatment of Diabetic Retinopathy Study (ETDRS), found laser photocoagulation to be a satisfactory means of slowing the retinopathy progression.2 A later version of this technique, the modified ETDRS, is the focal/grid photocoagulation protocol that is currently used by most retinal specialists.3 It is associated with a number of discouraging potential side effects, however, such as inadvertent foveal burn, enlarging scar formation, expanding scotoma, and choroidal neovascularization.4,5

ROLE OF ANTI-VEGF THERAPY

More recent studies have investigated the use of antivascular endothelial growth factor (anti-VEGF) treatment to halt or slow the progression of diabetic retinopathy in patients with diabetic macular edema (DME). Early indications from the RISE and RIDE studies report that ranibizumab (Lucentis, Genentech) rapidly and sustainably improved visual acuity and macular edema in patients with DME, with low rates of ocular or nonocular harm.6

A study by the Diabetic Retinopathy Clinical Research Network (DRCR.net) questioned the modified ETDRS treatment parameters. In comparing continuous wavelength laser with anti-VEGF treatment, the researchers noted that laser photocoagulation complemented anti-VEGF, but in a group of patients with central macular edema, laser alone did not provide sufficient treatment response.7 This is likely due to the restrictions on using a continuous wavelength laser in the foveal avascular zone.

TISSUE-SPARING LASER THERAPY

A new understanding of cell response to thermal injury has dispelled the previous theory that it is necessary to destroy retinal pigment epithelial cells to have a therapeutic effect,8,9 leading to the exploration of tissuesparing laser modalities. MicroPulse technology (Iridex Corporation) cuts the laser beam into a train of repetitive short pulses, preventing the buildup of thermal energy. Thus, instead of destroying tissue, the aim is to induce a stress response that results in antiangiogenic and restorative activity. A comparison of subthreshold MicroPulse diode laser and modified ETDRS laser photocoagulation in 62 eyes with center-involving, clinically significant DME showed the MicroPulse method to be as effective as the modified ETDRS parameters.10 In addition, MicroPulse treatment did not cause any change as determined by fundus autofluorescence, encouraging the use of the less aggressive approach. Long-term studies similarly demonstrated that MicroPulse laser treatment could effectively treat DME without laser-induced retinal damage.11

For me, one of the greatest benefits of the MicroPulse laser is that it allows the use of energy right over the fovea. Continuous-wave laser creates thermal damage to photoreceptors and can induce ischemia to the foveal avascular zone if it is applied too close to the fovea. Scotomas or scars may also form in the back of the eye that can expand over time. Subthreshold laser, which is a very light treatment of continuous-wave laser, also requires caution in how much and where it is applied. MicroPulse laser, on the other hand, sections the beam into little segments so that the heat generated is never sufficient to create a thermal burn within the retina. This allows a grid to be applied directly over the area of the edema, even if it overlies the central fovea. After treatment, there is no thermal uptake identifiable with fluorescein angiography or optical coherence tomography, nor is there any disruption of the retinal pigment epithelium from MicroPulse laser.

PATIENT PROTOCOL

I examine my patients with a 70.00 D lens and utilize OCT and fluorescein angiography when indicated. If clinically significant macular edema is visible, I then discuss the treatment options. I explain that continuous-wave laser photocoagulation was the gold standard for treatment. For focal DME, the laser is used to spot-weld the microaneurysms to seal them up and prevent them from leaking. In diffuse edema, a grid of laser therapy is applied over the area of edema to decrease the swelling. I then explain that there are some newer therapeutic options and explain how MPLT works. I also inform my patients that anti- VEGF medications can slow down the progression of the retinopathy and help decrease the edema.

If the edema is moderate to severe, I let the patient know that it might be in his or her best interest to undergo several sessions of anti-VEGF therapy first; it will provide a better effect faster, and if the swelling is reduced first, the therapy will last longer. The treatment I start with depends on the location and thickness of the edema as well as how symptomatic the patient is, but it generally includes a combination of both injections and MPLT. I feel very comfortable with MicroPulse as another adjunct of therapy because it does not create thermal damage. In the MicroPulse mode, I treat with a very high-density, lowintensity laser directly over the fovea, the location of most centrally occurring edema.

In my practice, I use the IQ 532 (Iridex Corporation) green laser. With a standard Mainster contact lens, I begin by placing a test burn in the continuous-wave mode using a 100-μm spot, 100 ms, and 100 mW. I then titrate the power up by 10 to 50 mW until a threshold burn is noted. I then switch to the MicroPulse mode and set it to a 5% duty cycle. I leave the spot size at 100 μm and double the duration and power settings. I apply a high-density, lowintensity grid treatment over the area of retinal edema. Figures 1 and 2 display OCT images of two patients I treated with MPLT.

TREATING THE WHOLE PATIENT

My geographic area is rural and has one of the highest obesity rates in the state of Michigan, and as a result, I have a high percentage of diabetic patients. Many of these patients are very hard workers, but have a tendency to delay seeking medical treatment, especially regarding their eyes. Many times, I first see a patient after he or she already has significant eye disease, requiring an aggressive treatment plan.

When dealing with diabetic patients, it is important to remember that this disease is not just in their eyes, but in their kidneys, their cardiovascular system, their nervous system, and, frankly, their entire body. I always begin by recommending that patients adopt healthy lifestyle habits, eat properly, lower their hemoglobin A1C levels, exercise, not smoke, and check that their family doctor or endocrinologist is monitoring them systemically. We work closely with family practitioners and internal medicine doctors to make sure they are informed every time we see their patients by sending an update on their status and treatments. We know from the Diabetes Control and Complications Trial (DCCT) that there is a 76% reduction in the risk of eye disease in patients who control their blood glucose levels.12

CONCLUSION

Our creed as physicians is to “first do no harm.” Although some of our laser therapies for DME have been effective, they have also caused significant adverse events. With MPLT, I feel much more comfortable treating my patients, because I know I can anticipate a successful result and avoid many of the side effects of traditional focal laser photocoagulation. With the ability to use anti-VEGF injections adjunctively, it is possible to personalize treatment for individual patients.

David D. Gossage, DO, is the founder of the Gossage Eye Institute in Hillsdale, Michigan, and is the ophthalmology residency director for Michigan State University, Hillsdale Campus. He has a financial interest in Iridex Corporation. Dr. Gossage may be reached at eyegoose@yahoo.com.

  1. American Diabetes Association. http://www.diabetes.org/diabetes-basics/diabetes-statistics/. Accessed on February 20, 2013.
  2. Early Treatment Diabetic Retinopathy Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. 1987. Ophthalmology. 94:761-774.
  3. Fong DS, Strauber SF, Aiello LP, et al. the Diabetic Retinopathy Clinical Research Network. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007;125:469-480.
  4. Schatz H, Madeira D, McDonald HR, Johnson RN. Progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. Arch Ophthalmol. 1991;109:1549-1551.
  5. Roider J. Laser treatment of retinal diseases by subthreshold laser effects. Semin Ophthalmol. 1999;14:19-26. 6. Nguyen QD, et al. Ranibizumab for diabetic macular edema: results from 2 phase iii randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801.
  6. Elman MJ, Aiello LP, Beck RW, et al. Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064-1077.
  7. Wilson A. Argon laser photocoagulation-induced modification of gene expression in the retina. Invest Ophthalmol Vis Sci. 2003;44:1426-2434.
  8. Dorin G. Evolution of retinal laser therapy: minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it? Semin Ophthalmol. 2004;19:62-68.
  9. Vujosevic S, Bottega E, Casciano M, et al. Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation. Retina. 2010;30(6):908-916.
  10. Luttrull JK, Sramek C, Palanker D, et al. Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode micropulse photocoagulation for retinovascular macular edema. Retina. 2012;32(2):375-386.
  11. White NH, Sun W, Cleary PA, et al. Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the Diabetes Control and Complications Trial. Arch Ophthalmol. 2008;126(12):1707-1215.