Since the ETDRS, laser photocoagulation has been the gold standard for the treatment of diabetic macular edema (DME). In recent years, there have been interesting developments in regards to pharmacologic options, particularly anti-VEGF agents, and these are positive advancements to expanding the treatment options for our patients. One important point to note about the clinical trials with anti-VEGF is that only patients with foveal involvement were included in these studies. So, for DME that does not involve the fovea, laser photocoagulation may continue to be the gold standard for treatment.
Anti-VEGF has shown good results for DME. The Diabetic Retinopathy Clinical Research Network (DRCR. net) Protocol I study in the United States and the RESTORE study in the United Kingdom and Europe both showed ranibizumab to be effective, both alone and in combination with laser.1,2
Even if we shift our treatment paradigm for DME to injecting anti-VEGF, I do not believe that we will discontinue our use of laser. After all, do we truly want to commit our patients to monthly, or even more frequent, injections for an extended period of time? Particularly for our younger patients, this could mean decades of injections. Just as having anti-VEGF agents as another option for patients is an advantage, so is having laser as an option. Considering that some of our patients may find it incredibly inconvenient to have multiple injections along with the burden that costly injections could place on health care systems, having more options, such as laser, may represent a good compromise.
Laser reduces frequency of injections
In reviewing the DRCR.net 2-year expanded study, I did not find any significant difference in the number of injections in the ranibizumab with prompt laser vs ranibizumab with deferred laser, but over the course of the study, 80% of all patients had received laser treatment. 1 The READ-2 study, however, did find that when laser was added to ranibizumab, patients required far fewer injections (4.9) over 24 months than with ranibizumab alone (9.3) with similar visual acuity results (6.80 letter gain and 7.70 letter gain, respectively).3 In addition, combining laser with pharmacotherapy can offer benefits of reduced chair time, cost, and inconvenience to the patient in regard to frequent injections.
works has evolved from direct coagulation of leakage in the retina as the main mechanism of action to learning that laser energy is absorbed by the retinal pigment epithelium (RPE), which changes the microenvironment, leading to the closure of microaneurysms and reduction of macular edema.
One of the long-standing issues with conventional laser is the concomitant damage and scarring that spreads over time, leading to future scotomas. Although 20/20 results can be achieved with conventional laser, what about overall retinal function? In addition to optical coherence tomography (OCT), fundus photography, and fluorescein angiography (FA), we now have microperimetry available to see deeper into how laser affects retinal sensitivity (Figure 1).
Based on microperimetry, we carried out a study on reading ability in patients who have DME. It's common for patients with DME who appear to have good visual acuity say that they cannot read. In our study, we found that patients with slower reading speeds had a reduction of contrast sensitivities, a reducing microperimetry, and a loss of fixation. Therefore, one can postulate that when there's scarring, there can be a reduction of retinal sensitivities. Quite often very faint scars in the beginning enlarge over time. After a year, they could be quite large; after 5 years the scars can be even more horrendous.
Continuous-wave pattern scanning is not MicroPulse
The subthreshold MicroPulse Laser Therapy (MPLT) technique delivers laser energy in pulses resulting in no visible scarring compared to conventional continuouswave (CW) laser treatment. According to Topcon, the PASCAL pattern laser system is able to deliver multiple spots at 50% of the visible threshold power to achieve similar subthreshold effects as MPLT. In my opinion, however, 50% PASCAL is not the same as MPLT. With 50% PASCAL—but not with MPLT—scarring can still be observed on fundus autofluorescence (FAF).
With MPLT, the laser energy is delivered in a train of repetitive microsecond pulses with adequate cooling time in between. The resulting total energy can be higher but no lethal photothermal effects are produced and no laser lesions are discernible on FA and FAF as reported by Vujosevic et al4 (See MicroPulse Technology: It's Not Your Classic Laser, page 15).
Benefits of 577 nm MicroPulse in Practice
In addition to Vujosevic et al,4 other authors have shown 810 nm MPLT effective in the treatment of DME5-7 (See Table 1) as well as other vascular disorders, such as macular edema due to branch retinal vein occlusion8 and central serous chorioretinopathy,9 with minimal or no collateral effects.
One of the more recent developments is the incorporation of MicroPulse laser technology in a 577 nm yellow laser system, such as the IQ 577 (Iridex) laser system, which offers both CW and MicroPulse modes. In my experience, I have found similar outcomes using 577 nm MPLT as with 810 nm MPLT for the treatment of DME. With 577 nm MPLT, I use a 5% duty cycle: laser on for 0.1 ms and off for 1.9 ms (See MicroPulse Laser Therapy: Parameters for Treating DME Using the IQ 577 Laser System). After I perform a test burn, I reduce power by 70%. These settings appear to be effective and do not produce scarring at any time post-treatment, which make subthreshold MPLT an ideal “repeatable” therapy (Figure 2). Similar to my experience using 810 nm MicroPulse, with 577 nm MicroPulse, I use a dense treatment pattern that is OCT-guided, so I do not specifically treat microaneurysms. Dense treatment means that we use confluent laser applications with overlapping spots. The entire edematous area is treated based on OCT.
Patient Selection Considerations
In my practice, MPLT is our routine practice for treating patients with DME. We also use it for treating macular edema due to retinal vein occlusions, and central serous chorioretinopathy. Recently, I have started treating small foveal cysts, which can cause mild visual loss but can get worse over time. These cysts are commonly associated with microaneurysms within 100 μm of the foveola, which is too close to be treated by conventional laser. Because MPLT does not scar, this is an ideal treatment.
When patients realize that there is no scarring and a much better safety margin with MPLT (than with conventional laser treatment), they are very accepting of the procedure, particularly if they've had prior conventional laser treatment. They are reassured that even if they move during treatment, it is actually very unlikely to be a problem.
577 nm MPLT Case Report
A 65-year-old white man was referred to me by his optometrist, who noted reduced vision OD in a routine examination. The patient had been on medication for type 2 diabetes for 15 years, his HBA1c level was 7.0, and his blood pressure was 140/70 with medication. His cholesterol was 4.8 mmol/l and he was taking a statin. His ocular status was mild nuclear sclerosis cataract and best corrected visual acuity of 20/40 OD and 20/20 OS. Figure 3 shows the OCT of the patient's right eye, preoperative (top) vs postoperative (bottom). Note the reduced macular edema 4 months postoperatively after a single treatment with MPLT.
Laser is still required in the majority of patients with DME, particularly those who do not have foveal involvement. Subthreshold MPLT, in my opinion, can be safely applied without producing retinal scarring at any time posttreatment, even in the treatment of cysts that are within 100 μm from the fovea. Further, in combination with anti-VEGF agents, MPLT can reduce the number of injections in the management of patients with DME, and without scarring, might get a better visual outcome.
Victor Chong, MD, FRCS, FRCOphth, is Consultant and Head of Department, Oxford Eye Hospital, University of Oxford, UK. He states that he is a consultant to Novartis, Pfizer, Allergan, Bayer, Regeneron, Iridex, and Alimera Sciences; a speaker for Heidelberg and Quantel; receives departmental research funding from Novartis, Pfizer, Alcon, Allergan, and Bayer; and has received equipment donation from Optos, Quantel, Iridex, and Carl Zeiss Meditec. Dr. Chong may be reached via email at email@example.com.
- 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(4):609-614.
- Mitchell P, Bandello F, Schmidt-Erfurth U, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118(4):615-625.
- Nguyen QD, Shah SM, Khwaja AA, et al. Two-year outcomes of the ranibizumab for edema of the macula in diabetes (READ-2) study. Ophthalmology. 2010;117(11):2146-2151.
- Vujosevic S, Bottega E, Casciano M, Pilotto E, Convento E, Midena E. Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation. Retina. 2010;30(6):908-916.
- Figueira J, Khan J, Nunes S, et al. Prospective randomised controlled trial comparing subthreshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema. Br J Ophthalmol. 2009;93(10):1341-1344.
- Lavinsky D, Cardillo JA, Melo LA, Jr., Dare A, Farah ME, Belfort R Jr. Randomized clinical trial evaluating mETDRS versus normal or high-density micropulse photocoagulation for diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(7):4314-4323.
- 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. 2012;32(2):375-386.
- Parodi MB, Spasse S, Iacono P, Di Stefano G, Canziani T, Ravalico G. Subthreshold grid laser treatment of macular edema secondary to branch retinal vein occlusion with micropulse infrared (810 nanometer) diode laser. Ophthalmology. 2006;113(12):2237-2242.
- Koss MJ, Beger I, Koch FH. Subthreshold diode laser micropulse photocoagulation versus intravitreal injections of bevacizumab in the treatment of central serous chorioretinopathy. Eye (Lond). 2012;26(2):307-314.