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QUESTION

WHAT IS MICROPULSE LASER AND WHAT CAN IT BE USED FOR?

Scott D. Walter, MD, MSc

Although anti-vascular endothelial growth factor (anti-VEGF) therapy has become the mainstay of treatment for many retinovascular diseases, laser therapy remains an important therapeutic option for many patients. In fact, more than 45% of patients enrolled in Protocol T received laser photocoagulation (focal, grid, or both) due to persistent diabetic macular edema (DME) despite 6 or more months of rigorous anti-VEGF therapy¹; whereas conventional focal or grid laser treatments involve retinal photocoagulation and resultant scar formation, newer treatment paradigms, such as micropulse laser (IRIDEX Corporation) and subthreshold continuous wave laser are intended to achieve therapeutic photostimulation of the retinal pigment epithelium (RPE) without photocoagulation of the overlying neurosensory retina. While we are still learning about the optimal indications and treatment parameters for this technology, I use micropulse laser as adjunctive therapy in a majority of my patients with persistent center-involving DME despite anti-VEGF therapy, and as primary therapy in select patients with macular edema from various causes.

Multiple factors contribute to the development of macular edema, including increased vascular permeability, an inflammatory milieu, and RPE pump dysfunction or exhaustion. Because macular edema is such a multifactorial disease, the use of multiple treatment modalities targeting different aspects of the disease pathophysiology may be required in order to achieve an optimal treatment response. Whereas anti-VEGF and steroid injections primarily target vascular permeability and inflammatory pathways respectively, the target of micropulse laser is the RPE.

Pigmented RPE cells absorb more laser energy than transparent retinal elements due to differences in their absorption spectra. Conventional laser photocoagulation works by heating the RPE and overlying photoreceptors to greater than 60°C, resulting in coagulative necrosis of ischemic retina, in turn reducing VEGF production. The postulated mechanism of action for micropulse laser is completely different. In vitro experiments suggest that therapeutic laser-tissue interactions may occur at lower, sublethal levels of RPE thermal stimulation: RPE cells upregulate heat shock proteins and other cellular rejuvenation pathways, essentially triggering tissue-healing responses without killing any RPE cells or overlying photoreceptors. This sublethal RPE stimulation is hypothesized to enhance the RPE’s ability to pump intraretinal fluid out of the retina, across the outer blood-retinal barrier, and into the choroidal outflow tract.

Conventional laser photocoagulation results in retinal whitening during the procedure and subsequent chorioretinal scar formation in the following weeks to months; however, when micropulse laser is performed correctly, there should be no visible changes to the retina during or after laser treatment. When applying irradiances less than 350 W/cm², there are no detectable signs of laser-induced retinal injury even by infrared, red-free, fundus autofluorescence, or optical coherence tomography imaging.2 In fact, micropulse laser can be directly applied to the fovea without causing treatment-associated vision loss or evidence of structural damage to the retina on multimodal imaging.³ For those accustomed to visible laser burns, micropulse laser may seem almost homeopathic due to the lack of a visible endpoint. For me, adopting this technology required a leap of faith and some patience to wait and see the treatment effects materialize. Efficacy can be assessed by monitoring reduction of macular thickness observed 1 to 2 months following treatment.

Subvisible laser-tissue interactions are achieved with the micropulse setting by modifying duty cycle. With continuous wave laser, the duty cycle is automatically set to 100%, and the laser emission is constant throughout the pulse duration. A 50% duty cycle means that the instrument delivers a series of interrupted (50% on/50% off) pulses; and a 5% duty cycles means that the instrument delivers a series of 5% on/95% off pulses. With a shorter duty cycle, a shorter pulse width limits the spread of laser-induced tissue hyperthermia, and a longer interval between pulses allows time for tissue cooling before the next pulse is delivered. MicroPulse Laser Therapy (IRIDEX) thereby allows selective thermal stimulation of the RPE in a finely controlled fashion.

I have experience performing micropulse laser with a frequency-doubled 577 nm neodymium-doped yttrium-aluminum-garnet laser (Fovea-Friendly MicroPulse Laser Therapy platform by IRIDEX) using a 5 % duty cycle and a pulse duration of 200 ms (Figure 29-1A). In the micropulse mode, there is a built-in repetition rate of 500 Hz, such that the duration of each micropulse is only 0.1 ms with a 1.9 ms rest between pulses (Figure 29-1B); therefore, each 200 microseconds (ms) laser emission consists of 100 micropulses totaling 10 ms on and 190 ms off (Figure 29-1C). The Arrhenius integral is a measure of tissue injury calibrated such that 1.0 equals the limit of cellular viability. With conventional laser photocoagulation, the Arrhenius integral exceeds 1.0, resulting in cellular coagulation and necrosis. However, the Arrhenius integral is approximately 10-fold lower with micropulse laser and subthreshold continuous wave laser; moreover, the energy uptake is more selectively targeted towards the RPE with micropulse laser (Figure 29-1D).

Micropulse capabilities are also available on an 810 nm diode laser platform (IRIDEX OcuLight SLx). A recent randomized controlled trial suggests similar safety and efficacy with either yellow (577 nm) or infrared (810 nm) wavelength micropulse laser.⁴ Subthreshold continuous wave laser treatment can be achieved by systematically reducing the laser energy by 70% after determining the threshold for a barely visible burn (PASCAL EndPoint Management System by Topcon). Whether any substantive differences exist between these 2 approaches to subthreshold laser is not yet established in the literature.

Micropulse laser has demonstrated efficacy for DME,^2–5 macular edema from retinal vein occlusion,² and central serous retinopathy (CSR).⁶ Many patients with these conditions demonstrate an incomplete response to anti-VEGF therapy, and I will often add micropulse laser as an adjunct to anti-VEGF treatment rather than switching anti-VEGF agents or resorting to steroids. In patients with center-involving DME, I routinely recommend micropulse laser to those who respond poorly or incompletely after 3 to 6 doses of anti-VEGF therapy. Not all patients respond to a single session, but most will demonstrate a significant reduction in macular edema if 2 or 3 treatments are performed over the span of several months. It is important to educate patients that the therapeutic response to micropulse laser is less immediate but often more durable than other treatment options. In my experience, micropulse laser can help to reduce injection frequency in patients treated concurrently with anti-VEGF therapy.

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