Initial Experiences With Yellow Navigated Laser and Microsecond Pulses in Patients With DME
A surgeon discusses a small study.
MARCUS KERNT, MD
The publication of results of the Early Treatment Diabetic Retinopathy Study established the clinical efficacy of laser photocoagulation in the treatment of diabetic macular edema. Although anti-VEGF agents, which have been shown to improve visual acuity in most patients within the first year of treatment,1-3 have in many cases replaced lasers as the first-line therapy for DME, laser photocoagulation remains an important option in the treatment of this disease.
In light of this continued relevance, we investigated navigated laser with and without microsecond-pulsed application, with the goal of improving accuracy and minimizing collateral damage.
Marcus Kernt, MD, is a consultant and retina specialist in the Department of Ophthalmology at Ludwig-Maximilians-University in Munich, Germany. He reports minimal financial interest as a medical adviser to OD-OS GmbH. Dr. Kernt can be contacted via e-mail at firstname.lastname@example.org.
NAVIGATED LASER PHOTOCOAGULATION
Recent studies in DME and other retinal conditions have demonstrated the shortcomings of traditional slit-lamp–based laser application compared to injection therapy, indicating only a minor, if any, synergistic effect in combination therapy.1,2 This effect may be attributable to the limited accuracy of the manual procedure and the less-than-complete treatment in everyday clinical practice.
Navigated retinal laser therapy was introduced to facilitate comprehensive image-guided planning, and it also allows for significantly greater accuracy in laser spot application to areas of edema, compared to traditional laser treatment.
The Navilas Laser System (OD-OS, Irvine, CA) is the first navigated retinal laser to reach the clinic. It integrates fundus imaging, including true color and fluorescein angiography, with computer-based, image-guided retinal laser therapy.4
Greater accuracy, acceleration of treatment, and a reduced retreatment rate with this new approach have been demonstrated in DME and proliferative diabetic retinopathy patients. Additionally, Navilas has proved successful in the treatment of retinal vein occlusions, central serous chorioretinopathy, polypoidal choroidal vasculopathy, idiopathic perifoveal telangiectasia, and choroidal neovascularization.4
However, one drawback of ETDRS laser photocoagulation is that, to ensure a treatment effect, the laser parameters must be adjusted to inflict permanent thermal damage to retinal tissue, leading to localized loss of retinal function and a varying degree of scarring. Formerly seen as the lesser of two evils, this factor alone has driven many ophthalmologists away from laser to anti-VEGF in recent years.
Given the chronic nature of anti-VEGF treatment and the high rate of anti-VEGF nonresponders, the development of novel laser modalities has continued, including microsecond pulsed lasers, which deliver a pulse train rather than a continuous wave (CW) laser beam to heat the retinal tissue to values below the coagulation threshold. This process results in thermal stimulation, rather than thermal retinal damage.5
NAVIGATED LASER PHOTOCOAGULATION WITH 577-NM AND MICROSECOND PULSING
In 2014, a Navilas with yellow 577-nm laser and the option to perform navigated microsecond-pulsed (MSP) treatments was introduced. The yellow wavelength is preferred by a number of physicians due to its reportedly lower scatter and a better absorption profile with peak absorption in melanin and oxyhemoglobin and minimized absorption by macular pigment.
Further, a more dramatic impact on therapy can be expected when laser energy levels are lowered below the coagulation threshold. Initial results for conventionally applied subthreshold laser, including microsecond pulsed laser, indicate that it has some efficacy in treating retinal disease.
Using the navigated MSP setting of the Navilas 577+, a large number of invisible, low-intensity laser effects can be applied for the first time rapidly and precisely to the retina without any undesired gaps or overlaps. Expectedly, at approximately 10% to 30% of the energy applied per spot as compared to conventional laser, the effects of MSP laser are invisible to the surgeon using slit-lamp–based technology.
I think we would all agree that it is a significant challenge to deliver a large number of laser spots — often more than 200 — without any visual feedback. Although this skill has been mastered by some, it remains limited to only a few surgeons, and the actual application scheme of the therapy varies between surgeons and clinics, as is clearly the case with conventional lasers.
Fortunately, with the Navilas, laser photocoagulation can be digitally preplanned using imported OCT images and applied in an evenly distributed confluent pattern using the digital spot documentation of the system.
If the pattern boundary is tied to a certain thickness threshold, the MSP treatment is easy to standardize and becomes accessible to novice users who may otherwise shy away from focal lasers.
EXPERIENCE IN DME
We have used the Navilas navigated laser system in both the university clinic and in private practice for several years and with good success. For example, we recently conducted a 12-month, prospective, comparative cohort study of 66 patients with DME, in which 34 patients were treated with combination therapy (ranibizumab [Lucentis, Genentech, South San Francisco, CA] plus navigated laser photocoagulation), and 32 patients were treated with ranibizumab monotherapy.
The findings showed that, while both navigated laser combination therapy and ranibizumab monotherapy provided similar improvements in mean best-corrected visual acuity letter score, in the combination group, significantly fewer injections were required after the initial injection loading phase.
While randomized, controlled trials are under way to further evaluate this kind of combination therapy, the vision for the future is to achieve comparable results with no detectable collateral damage.
On the basis of this experience, we were eager to evaluate and compare the efficacy, safety, usability, and effects of the new 577-nm yellow navigated laser with or without navigated MSP vs 532-nm green navigated laser in DME patients.
We undertook an initial case series of 14 eyes of 12 consecutive patients with center-involving DME. Nine eyes were treated with Navilas 532-nm (five eyes) and 577 nm (four eyes) CW laser photocoagulation to a barely visible effect.
Five additional eyes were treated with OCT-guided 577-nm navigated MSP therapy (confluent pattern, 100 µm, 100-µsec pulses, 5% duty cycle, 100-msec envelope pulse duration, titration with CW to barely visible effect, power values doubled/switch to MSP). Microperimetry analysis of retinal sensitivity was conducted on individual locations following image registration with Navilas treatment documentation (Figure 1).
Figure 1. Study methodology.
Both CW modes (green and yellow) created visible effects after titration. A case-by-case comparison indicated that the laser spot boundaries appeared subjectively more defined with the yellow 577-nm laser, but as expected, both modalities were very similar.
Our findings further confirmed previous reports that the yellow laser required less energy to create barely visible effect than green laser; power settings of 98 (±9.25) mW for 532 nm and 84 (±19.86) mW for 577 nm; the higher laser power variation in the yellow group may be attributed to the learning curve associated with this new laser technology.
The mean power setting for MSP was 170 (±32.84) mW after doubling. At a 5% duty cycle, no visible effects could be observed (Figure 2). Retinal sensitivity immediately after treatment remained higher with the yellow laser than with the green laser and unchanged after subthreshold yellow laser exposure (2.8±2.7 dB with 532 nm, -0.5±24.3 dB with 577 nm, and 0.05±4.0 dB with 577 nm MSP; Figure 3). Importantly, no adverse effects were observed.
Figure 2. Typical treatment plans and differences in laser effects.
Figure 3. Navigated analysis of retinal sensitivity after laser exposure.
Employing navigated laser in the treatment of retinal disease provides numerous advantages over conventional slit-lamp laser coagulation, including fast application of laser spots through prepositioning, precise, confluent and complete coverage of desired treatment areas, and integration of all imaging modalities to allow for the creation of a complete digital treatment plan.
Our study, the first-ever comparison of three different navigated laser treatment parameters, indicates that all laser modalities could safely and easily be applied in a standard clinical setting. However, the navigated yellow 577-nm laser required less laser power to create a barely visible effect than the 532-nm laser and appeared less detrimental to retinal function.
Additionally, the navigated MSP laser did not produce visible effects and did not appear to affect retinal function at the settings chosen (5% duty cycle corresponding to 100 µsec on- and 1,900 µsec off-time/100 msec envelope pulse duration/double power of titration burn average of ~170 mW laser power). Actually, these results encouraged me to increase the power up to three-fold the value for the titration burn in patients eligible for standard grid laser therapy.
Although this study was undertaken in DME patients, it would appear that navigated yellow 577-nm laser with/without MSP may represent a tissue-friendly option in the management of retinal disease in general, thus warranting further investigation into optimal dosing and therapeutic efficacy. RP
1. Elman MJ, Bressler NM, Qin H, et al; Diabetic Retinopathy Clinical Research Network. Expanded 2-Year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011;118:609-614.
2. Mitchell P, Bandello F, Schmidt-Erfurth U, et al; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118:615-625.
3. Brown DM, Nguyen QD, Marcus DM, et al; RIDE and RISE Research Group. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013;120:2013-2022.
4. Kernt M, Ulbig M, Kampik A, Neubauer AS. Navigated laser therapy for diabetic macular oedema. Eur Ophthalmic Rev. 2013;7:127-130.
5. Luttrull JK, Dorin G. Subthreshold diode micropulse laser photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular edema: a review. Curr Diabetes Rev. 2012;8:274-284.