Long-term outcomes support superior safety of subvisible diode micropulse

Data from a 10-year study suggest that subvisible diode micropulse with a small spot size and a low duty cycle treats retinal vascular disease with superior safety.

Jeffrey K. Luttrull

Damage associated with conventional laser therapy in treating retinovascular macular edema may be avoided through the use of subvisible diode micropulse, a retrospective review found.

According to Jeffrey K. Luttrull, MD, first study author, invisible retinal phototherapy, achieved by low-intensity, high-density subthreshold diode micropulse photocoagulation (SDM), represents a paradigm shift in retinal treatment.

“SDM is a radical departure from and challenge to conventional thinking about retinal photocoagulation for retinal vascular disease. Big change is often slow to be accepted, but I think that after almost 12 years we have reached the tipping point,” Dr. Luttrull told Ocular Surgery News.

Low-intensity exposure, or micropulsed 810-nm diode laser at low duty cycle, aims to enhance tissue selectivity and minimize heat spread and accumulation, preventing thermal retinal injury. This in turn allows for high-density coverage, which involves application of contiguous small-sized, short-duration spots that maximize heat dissipation, minimize heat accumulation, and maximize the therapeutic effect, the study authors said.

“We show that SDM done a particular way — small spot size and low 5% duty cycle — is harmless, without any evidence of laser-induced retinal damage at any point during or after treatment. … Because of the safety, we can treat earlier, more thoroughly, repeatedly if necessary and in conjunction with drugs for broad indications,” Dr. Luttrull said.

Discovery of SDM

Dr. Luttrull began using SDM in April 2000 when his argon laser stopped working the same day his Iridex 810-nm laser arrived. Not wanting to replace the argon laser, he decided to try the new laser’s micropulse mode. He applied this technique and arbitrarily chose parameters that ended up being safe and effective.

“SDM came about like most game-changing discoveries: through the attempt to solve a problem — no argon laser — and a combination of good intuition, good luck and good observation without fear of being unconventional,” Dr. Luttrull said.

Initially disconcerted by the lack of visible laser lesions, he would treat one eye and request patient feedback before moving on to the fellow eye a week later.

“Without exception, patients reported subjective improvement,” he said. “You never heard this after conventional argon laser treatment because, if anything, argon patients were usually worse early after treatment. This kept me performing the procedure until I started seeing clinical improvement at 6 to 12 weeks and thereafter.”

Methods, results

In their study, Dr. Luttrull and colleagues reviewed data for 212 eyes with diabetic macular edema and 40 eyes with branch retinal vein occlusion that were followed for a median of 47 months (range: 3 to 120 months) between April 2000 and January 2010. Arrhenius formalism enabled computational modeling of laser-induced retinal thermal effects resulting from SDM.

Of 168 eyes treated at an irradiance of less than 350 W/cm² (or a 5% micropulse duty cycle), none experienced retinal damage. However, seven of 84 eyes treated with at least 590 W/cm² (or a 10% to 15% micropulse duty cycle) experienced damage (P = .0001).

“We demonstrated that even a slight increase in duty cycle dramatically increases the risk of inadvertent and unnecessary retinal burns. We showed that if there are inadvertent burns, they are visible right away; no late lesions develop with an average of 4 years’ follow-up,” Dr. Luttrull said.

In a sub-analysis of 62 eyes treated for diabetic macular edema and evaluated preoperatively and postoperatively with spectral-domain optical coherence tomography, no retinal injury occurred for either SDM alone or SDM combination therapy groups during a median follow-up of 12 months.

“We also showed that computation models of tissue hyperthermia are consistent with and echo our clinical observations of the safety and efficacy of SDM treatment and the importance of keeping the duty cycle low and the spot size small to avoid retinal burns,” he said.

Mechanism of action

SDM may affect expression of locally acting cytokines, which influence development of diabetic retinopathy complications, Dr. Luttrull said.

“In the absence of laser-induced retinal damage, it seems clear that SDM is somehow stimulating the target tissue — the retinal pigment epithelium — to behave differently, more normally, most likely by altering cytokine expression. This phenomenon is well known in other cell types,” he said.

All tissue exposed to SDM is affected therapeutically rather than just the surviving cells at the edges of burns induced by conventional therapy, according to Dr. Luttrull.

“Laser-induced retinal damage is not only not therapeutic but actually represents an unnecessary and undesirable side effect of treatment,” he said. “It is helpful to remember that the association between retinal burns and a therapeutic benefit for retinal vascular disease has been circumstantial, while the association between retinal burns and the risks and side effects of treatment has been clear.” – by Michelle Pagnani

References:

The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macula edema in branch vein occlusion. Am J Ophthalmol. 1984;98(3):271-282.

Diabetic Retinopathy Study Research Group. Preliminary report on the effects of photocoagulation therapy. Am J Ophthalmol. 1976;81(4):383-396.

Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103(12):1796-1806.

Flaxel C, Bradle J, Acott T, Samples JR. Retinal pigment epithelium produces matrix metalloproteinases after laser treatment. Retina. 2007;27(5):629-634.

Gao X, Xing D. Molecular mechanisms of cell proliferation induced by low power laser irradiation. J Biomed Sci. 2009;16(1):4.

Luttrull JK, Sramek C, Palanker D, Spink CJ, Musch DC. Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode micropulse photocoagulation for retinovascular macular edema. Retina. 2011;doi:10.1097/IAE.0b013e3182206f6c.

Jeffrey K. Luttrull, MD, can be reached at 3160 Telegraph Rd., Suite 230, Ventura, CA 93003; 805-650-0664; email: jkluttrull@aol.com.

Disclosure: Dr. Luttrull has no relevant financial disclosures.

Even in the age of retinal pharmacotherapy, laser plays an important role in select cases of macular edema. Recently, pulse subthreshold laser has been used to treat diabetic macular edema and macular edema due to branch vein occlusion, and several studies suggest that it is as effective as traditional laser with reduced treatment-related consequences. Although the exact mechanism of action is unclear, subthreshold laser likely works by selectively injuring the retinal pigment epithelium, which then modulates local cytokine and growth factor expression during the healing process.

In this prospective, longitudinal study, the authors found a significant reduction in central foveal thickness in patients who received micropulse laser. Most interestingly, the vast majority of treated eyes had no evidence of retinal damage on fundus autofluorescence and fluorescein angiography. Larger, randomized trials will need to be performed before this treatment strategy using this particular wavelength is widely adopted. However, the concept of subthreshold laser remains intriguing and should be pursued further.

– Sunir J. Garg, MD, FACS
Associate Professor of Ophthalmology Wills Eye Institute
Disclosure: Dr. Garg has no relevant financial disclosures.