Argument against subthreshold laser for DME


Efficacy and practical limitations of subthreshold laser treatment for diabetic macular edema.


Efficacy and practical limitations of subthreshold laser treatment for diabetic macular edema.



By Cheryl Guttman Krader; Reviewed by Lloyd Paul Aiello, MD, PhD

Chicago-Subthreshold lasers should not be considered an ideal treatment for diabetic macular edema (DME), according to Lloyd Paul Aiello, MD, PhD.

“The idea that subthreshold laser treatment may not cause substantial or permanent structural changes in the retina is attractive,” said Dr. Aiello, professor of ophthalmology, Harvard Medical School, Boston, MA. “However, there are multiple factors that limit the importance of this treatment in the current management of DME.”

Efficacy and safety of laser photocoagulation

The benefit of focal/grid laser treatment for DME, Dr. Aiello said, is not as rapid or great as what can be achieved with antiVEGF injections.

Nevertheless, patients can achieve significant gains in vision and reductions in central subfield thickness over time, and without substantive visual sequelae from the laser treatment.

There has also been relatively few randomized controlled trials investigating this technique for treatment of DME, Dr. Aiello said.

The results from those reported do not indicate subthreshold laser treatment provides any major visual acuity improvement compared with standard laser approaches.

The subthreshold laser treatment also has some practical limitations: it is difficult to tell where the treatment was performed, and therefore difficult to assess treatment adequacy, location, efficacy, or retreatment areas.

The availability of nondestructive, pharmacological approaches for treating DME is another issue to consider.

As shown by results from the phase III RISE and RIDE studies investigating ranibizumab (Lucentis, Genentech), anti-VEGF injection results in marked visual improvement in the large majority of patients with DME.

In addition, outcomes from the protocol I study indicate that adding lasers when initiating anti-VEGF therapy may not be beneficial in the long term.

In the latter study, patients who were randomly assigned to anti-VEGF injection with prompt laser had a significantly lower visual outcome at 3 years than those who were assigned to anti-VEGF therapy with deferred laser. protocol I results also showed more than half of patients in the anti-VEGF plus deferred laser group (54%) received no laser treatment by the end of 3 years.

“If the idea for using subthreshold treatment is to laser as little as possible, it begs the question, ‘why laser at all?’” said Dr. Aiello, who is also head of Section of Eye Research and director of Beetham Eye Institute, Joslin Diabetes Center, Boston. “Indeed, as seen in protocol I, we are finding with antiVEGF therapy that the need for laser is markedly reduced.”

Laser technology currently works for treating DME with no major sequelae, Dr. Aiello.

“(The) subthreshold laser is difficult to visualize, has limited randomized trial data to support its use, and no clear evidence at this time that it provides a better visual acuity outcome,” he said.

The need for focal/grid laser treatment has also been reduced by the emergence of VEGF inhibition and steroids, Dr. Aiello said.

“Therefore, the answer to the question of whether subthreshold laser is currently an important treatment for DME has to be no,” he said.

Lloyd Paul Aiello, MD PhD


Dr. Aiello is a consultant to Genentech and scientific founder of Kalvista, which is developing pharmaceutical treatment for DME. He has no financial interest or competing financial interest in any laser technology.


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