Laser therapy maintains position as key DME treatment option


Amid the introduction of new technologies, device still playing critical role

Laser continues to play an important role in diabetic macular edema amid an increasing reliance on anti-VEGF drugs.

Reviewed by Elias Reichel, MD

Laser remains a critical component in the treatment of diabetic macular edema (DME) amid an increasing number of new devices designed to deliver subthreshold laser. “Laser still plays a very important role in the treatment of diabetic macular edema despite our reliance on anti-vascular endothelial drugs,” said Elias Reichel, MD, professor of ophthalmology and vice chairman, Tufts University School of Medicine, Boston.

The Diabetic Retinopathy Clinical Research Network ( Protocol I study supports that statement, with patients treated with deferred laser therapy, defined as application between 24 weeks, fared the best. Over the course of two years, Dr. Reichel pointed out, there was a benefit in those patients compared with those treated promptly with laser and accompanied by anti-VEGF or steroid therapy and sham treatment. As an additive therapy, laser is helpful even in Protocol T compared to primary VEGF therapy.

Subthreshold laser is defined as that which shows no signs of damage to the clinical examiner, Dr. Reichel explained, and demonstrated what constitutes subthreshold laser therapy. In a patient with 20/50 visual acuity (VA), fluorescein angiography (FA) showed diffuse leakage through the macula, and optical coherence tomography (OCT) showed the cystic change. The patient was treated with micropulse laser in the left eye with the setting of 400 mW, 200 μm spot size, for 200 ms; 343 spots were applied, which is seven applications on a 7 x 7 grid.

An important factor in this treatment was the 5% duty cycle, which has been able to perform subthreshold laser treatment safely even with application to the fovea, he emphasized. Four months after laser treatment, the VA was 20/30. No changes resulting from the treatment or pigmentary changes were visible on fluorescein angiography. The foveal appearance on OCT was more normal than before treatment with some small central cysts visible.

All of the basic science research has supported subthreshold laser; however, the clinical efficacy is supported only by limited case series, which provided data on Micropulse and Endpoint Management (Topcon Medical Systems, Inc.), he commented. The usefulness of laser demonstrated in the concerned conventional laser photocoagulation only.

“It is important to understand that micropulse therapy can be applied to the fovea in patients with DME, but Endpoint Management and microbubble disruption avoids the fovea,” he said.FDA approved devices

The devices approved in the United States all use yellow or green wavelengths. Three micropulse devices have been approved. They include Micropulse (IRIDEX), Quantel Laser (SubLuminal), and Lumenis (SmartPulse). Topcon makes continuous-wave technology (Endpoint Management). Ellex manufactures Retinal Rejuvenation Therapy (2RT), a microbubble disruption therapy.

Compared with conventional laser-characterized by a solid block of laser application over time (100 or 200 ms) accompanied by a temperature increase-the heat produced is absorbed by the retinal pigment epithelium (RPE) and choriocapillaris and is in turn diffused into the neurosensory retina with the potential to cause damage. Micropulse therapy is a packet of energy that is delivered over 200 ms; the laser is on 5% of the time and off 95% of the time in the individual packets.

“There is an increase in temperature; the retinal tissue heat, but they cool rapidly, and there is no diffusion damage to the neurosensory retina,” Dr. Reichel said. According to Dr. Reichel, Endpoint Management differs from Micropulse because it relies on the Arrhenius integral and describes the changes in temperature in time and space over biologic tissues in response to laser energy.

“This technology uses a short-pulse duration within a narrow therapeutic window and the biologic damage is proportional to the laser power,” he explained. The algorithm that is used in this technology results in a spot that shows barely visible damage. The power setting then drops 70% to reach the perfect level of treatment energy and duration for surgeons to use.

Dr. Reichel provided an example in with the energy level was about 30% for 12 ms. Microbubble disruption provides selective targeting of individual RPE cells. The microbubbles around the melanosomes expand, causing intracellular damage resulting in individual cell apoptosis.

The adjacent RPE cells migrate, divide, and produce new RPE cells. Dr. Reichel commented that there are no landmark burns in these technologies except for the those produced by the algorithm used in Endpoint Management. The others rely on physician titration, which necessitates that they observe retinal burns.Practical tips

According to Dr. Reichel, physicians use the correct preset, confirm the correct treatment mode and make sure the laser is not set to the conventional treatment mode. They also should confirm the 5% duty cycle setting when using Micropulse and be aware of landmarks and placement of treatment spots. “Several different subthreshold technologies are available,” he said.

However, Dr. Reichel noted that the administration of subfoveal therapy is only possible with Micropulse.

“The ability to perform Micropulse and the recommended titration and the appropriate protocol and settings should be confirmed with the manufacturer,” he concluded.

“No clinical trials have been conducted to confirm the superiority or noninferiority of Micropulse to conventional laser with any of the subthreshold technologies.”


Elias Reichel, MD
Dr. Reichel is a consultant to Lutronics, a member of the speakers’ bureau for IRIDEX, and received a research grant from Lumenis.

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