PEER REVIEWED

Evolution of Retinal Laser Photocoagulation: Pattern, Navigated, and Micropulse

Matching modality to pathology

KHUSHBOO K. AGRAWAL, MD • RONALD C. GENTILE, MD, FACS, FASRS

Although laser (actually an acronym, LASER) is a universally recognized term, the first device in the evolution of the laser, the MASER, is far less known. The MASER amplified microwaves and was invented in 1953 by the Nobel laureate physicist Charles Hard Townes.

During the same period in which Dr. Townes attempted to create a pure beam of light or laser, Gerhard Meyer-Schwickerath, a German ophthalmologist, was experimenting with an optical method to coagulate the retina using a focused beam of light.^1,2

Dr. Meyer-Schwickerath, the father of modern retinal photocoagulation, was inspired by his observations of solar eclipse retinopathy. He initially worked on devices that attempted to harness sunlight.

Realizing the limitations and unpredictability of sunlight, Dr. Meyer-Schwickerath collaborated with a physicist, Hans Littmann at Carl Zeiss Laboratories, to develop the xenon arc lamp photocoagulator.^2-4

The xenon arc lamp photocoagulator produced a bright white light that closely mimicked sunlight, and it became commercially available in 1956. This device revolutionized the treatment of myriad retinal disorders, and became an indispensable tool in the armamentarium of retinal specialists worldwide.

In 1960, four years after the xenon arc lamp photocoagulator became commercially available, Theodore Maiman, an engineer and physicist, invented the first operating laser, which used a synthetic pink ruby crystal and xenon flash lamp.

Dr. Meyer-Schwickerath’s ideas, combined with advances in lasers was a natural fit, opening the door to many more options using a laser light source to photocoagulate the retina.

LASER VS XENON ARC PHOTOCOAGULATION

Because the light source from laser is coherent and monochromatic, it offered many practical advantages over the gas discharge lamp’s electric light. Although the landmark Diabetic Retinopathy Study (DRS) of the 1970s is commonly cited for photocoagulation’s ability to reduce severe visual loss in diabetic retinopathy, the study also compared the argon blue-green laser to Dr. Meyer-Schwickerath’s xenon arc photocoagulator.

Argon laser and xenon arc photocoagulation were both found to decrease the likelihood of severe vision loss in proliferative DR. When the argon laser-treated eyes were compared to the xenon arc-treated eyes, the former had less early vision loss, peripheral vision loss, and progression of pre-existing tractional retinal detachments.

The DRS results, in addition to the relatively awkward inefficiency of the xenon arc photocoagulator, paved the way for the development of lasers for retinal photocoagulation, including the ruby, argon, and krypton lasers.⁵

The physical design of these latter lasers included coupling them to a slit lamp with rotating mirrors and a mobile joystick, which allowed them to project a single aimed beam onto the retinal surface.⁵

Additional advances in laser technology, particularly with solid-state lasers and dye lasers, offered many other advantages. Compared to the early-generation lasers, these newer lasers were air-cooled, plugged into standard 110- to 220-V outlets, incorporated a broader range of wavelengths, and could be portable.

Current ophthalmic lasers operate at a very broad range of wavelengths, the most commonly used ones of which are green (532 nm), yellow (561 nm, 577 nm), red (660 nm, 670 nm), and infrared (810 nm).⁶

Advances in lasers have also allowed manufacturers to incorporate other features into lasers that allow for greater operator efficiency, accuracy, and, in some cases, patient safety. The features reviewed include pattern laser, navigated laser, and micropulse laser.

PATTERN LASER

Pattern lasers evolved to make laser treatment more comfortable and efficient then the conventional single-spot delivery lasers. The Pattern Scan Laser, known as the PASCAL (Topcon, Santa Clara, CA), was introduced in 2006 by Blumenkranz and associates.

The PASCAL is a 532-nm frequency-doubled Nd:YAG solid state laser with a semiautomated system that delivers multiple laser spots with a shorter pulse duration in a preset pattern.⁷ This shorter pulse duration requires less energy and produces less choroidal heating, thereby reducing patient discomfort.^7-9

The laser can deliver up to 56 spots in less than 0.6 seconds with a single foot pedal depression.^6,10 If the foot pedal is released before completion of the pattern, the pattern is aborted, and another similar pattern is prepared for delivery. The predetermined pattern (Figure 1) allows for more homogeneous and precise laser spot delivery, which theoretically reduces visual field loss and overall retinal injury.⁹

Figure 1. Pattern photocoagulation in the treatment of proliferative diabetic retinopathy.
COURTESY OF SEENU HARIPRASAD, MD

In addition, this type of pattern delivery saves time, increases efficiency, and improves clinic flow.¹¹ Nagpal et al reported that the advantages of pattern laser over conventional laser treatment included shorter treatment times, less pain, and less collateral damage.¹²

Variations

In the nine years since the PASCAL laser gained FDA approval, several manufacturers have developed their own versions of pattern laser delivery (Table, page 26). Although the premise is the same and includes the application of laser in preset patterns (grids, arcs, arrays) with a single foot pedal click, variability does exist in the technical parameters among different models.

For example, Lumenis (Yokneam, Israel) has introduced a technology, called the Array LaserLink, which allows for spots ranging from 100 to 500 µm in size for each of its patterns. Nidek (Fremont, CA) has more than 20 patterns available in its multicolor scan laser model.

In contrast, Ellex’s (Minneapolis, MN) Rapide laser model has six predetermined patterns, allowing for a maximum diameter up to 6,000 µm to accommodate the curvature of the eye, with a maximum pattern duration of 750 ms. The Supra Scan laser by Quantel Medical (Bozeman, MT) provides different types of patterns for panretinal photocoagulation, depending on where in the periphery the laser is to be applied (ie, square for midperiphery, arc for the far periphery).

The Iridex (Mountain View, CA) patterns include a modifiable grid, which can range from 2x2 to 7x7, for maximum laser spot delivery. The Navilas has three preset patterns, each with its own modifiable parameters.

The Navilas’s rectangle grid ranges from 2x2 to 5x5 with a spot size of 50-500 µm; the spots can be spaced 0 to 4 spots away from each other. Its ring pattern can vary in inner diameter from 300 to 3,000 µm, with a spot size of 50-500 µm (75-750 µm for PRP) and spaced 1-2 spots apart. The Navilas’s arc pattern has similar features to the ring pattern, with the ability to vary its angle of rotation.

Limitations

Limitations of pattern laser treatments exist. Some pattern lasers have been shown to be less effective than single-spot argon laser delivery in preventing recurrence of and inducing regression of neovascularization in patients with high-risk proliferative diabetic retinopathy.¹³ This is believed to be a result of the smaller burns created by the pattern. In addition, large pattern arrays may not deliver uniform laser intensity, especially if the curvature of the eye has not been factored into the treatment plan and/or peripheral media opacities are present. Certainly, more studies and user experience are necessary to establish the most ideal parameters for laser treatment with pattern laser delivery systems.

NAVIGATED LASER

Navigated laser (Navilas; OD-OS, Irvine, CA) was introduced in 2009, as a unique platform that combines color, infrared, and fluorescein fundus imaging to produce the most precise laser treatment.⁷ It contains a camera and computer-based imaging system that obtains real-time high-resolution images at a rate of 25 images per second.

The field of view for focal laser is 50º (optical resolution of 1,280x1,024 pixels), and the field of view for panretinal laser is 80º.¹⁴ The physician imports the fluorescein and infrared images onto the computer screen and overlays the live fundus image on these to plan the treatment area. The optic nerve and center of the fovea are marked as areas not to be treated (Figure 2).¹⁵ Eye tracking software improves the precision of laser treatment.

Figure 2. Treatment plan on Navilas for a 54-year-old woman with DME. Fluoroscein angiogram (top left), color fundus image (top right), FA superimposed on fundus image (bottom left), and treatment initiation (bottom right).
COURTESY OF RICHARD B. ROSEN, MD

The system includes single-spot delivery and preset patterns. Although the original Navilas system contained a 532-nm frequency-doubled solid-state laser, OD-OS received FDA approval for a 577-nm (yellow) micropulse laser in February 2015.

Comparing pattern and navigated lasers, Chhablani et al found that the navigated laser produced more uniform burns, less pain, and an overall shorter treatment time than the pattern laser in eyes with PDR undergoing PRP.⁷

The limitations of navigated laser treatment include its longer learning curve and higher cost. Because the technology is new, it does not use a slit-lamp/contact lens–based laser delivery method. The system is also dependent on obtaining high-quality fluorescein images that may be difficult in patients with media opacities.¹⁶

MICROPULSE LASER

Micropulse laser uses a continuous-wave laser beam that is chopped into short, repetitive microsecond pulses, allowing tissue to cool between pulses and reducing thermal buildup.¹¹

The laser “on” time is the duration of each micropulse, and the “off” time is the time between micropulses that allows for heat reduction and thermal isolation of each pulse.¹⁷ The ratio between “on” and “off” time is also known as the duty cycle. The lower the duty cycle is, the greater the heat reduction is. Duty cycle can be adjusted and is commonly set at 5% for subthreshold laser.

Micropulse lasers, on average, have exposures times that are 50 times less than conventional lasers. Because thermal tissue damage is proportional to exposure time, a short duty cycle would only be expected to increase the temperature of the retinal pigment epithelium.¹⁸

Multiple lasers that are commercially available have micropulse capability (Table). It has been used with infrared (810 nm), yellow (577 nm), and green (532 nm) wavelengths.

Micropulse lasers are primarily used for treating macular diseases because they avoid laser-induced thermal damage by improving tissue selectivity and minimizing lateral heat spread.¹⁷ Electron microscopy studies have shown that laser power as low as 10% to 25% of visible threshold power will only affect the RPE while sparing the overlying retina.¹

Eyes treated with micropulse lasers do not exhibit damage to the photoreceptors and/or choriocapillaris. Micropulse-laser-treated eyes do not develop the postlaser pigmentary changes typically seen with threshold laser treatments,^19,20 avoiding scotoma, color vision loss, and loss of contrast sensitivity.^20,21 Due to the safety of micropulse, it can be repeated without limit.

Micropulse laser has been used to treat a variety of macular diseases, including diabetic macular edema, retinal vein occlusion, PDR, central serous chorioretinography, retinal macroaneurysms (RAMs), radiation retinopathy, juxtafoveal telangiectasia, and recalcitrant uveitic CME.

In 1997, Friberg and Karatza reported their study on micropulse laser with an infrared (810 nm) diode laser in the treatment of DME, RVO, and choroidal neovascularization from age-related macular degeneration. They treated 126 patients and found micropulse laser to be effective but more difficult to use than the argon laser.²²

Subthreshold Micropulse Laser

Since its inception, the micropulse laser delivery method has been modified to deliver “subthreshold” treatment, which applies the same repetitive short pulses without a clinically visible endpoint.

The mechanism of subthreshold micropulse laser is believed to be due to the release and/or downregulation of various factors from recovering RPE cells.¹¹ These factors have been postulated to include cytokines, VEGF, heat shock protein, pigment epithelium-derived factor (PEDF), and matrix metalloproteinase.¹⁰ Because downregulation of VEGF can occur at low laser exposures, subthreshold micropulse laser may be as effective as a clinically visible lesion.¹⁹

Micropulse laser spots do not appear on fluorescein angiography following treatment; this is believed to represent intact RPE tight junctions.²³ Subthreshold micropulse laser may promote healing of the retina, without causing damage.

EVIDENCE: MICROPULSE VS CONVENTIONAL LASER

Although the majority of the literature on micropulse laser technology has been limited to the results of small-scale, retrospective, uncontrolled studies, there has been a minority of randomized, control trials evaluating the efficacy of this laser in different retinal vascular conditions.

Lavinsky et al found threshold micropulse laser to be superior to standard mETDRS laser in eyes with DME; micropulse-treated eyes gained more vision and had less vision loss than mETDRS-treated eyes. In contrast, Figureia et al found subthreshold micropulse laser and conventional green laser equally effective in the treatment of DME, but they did report a trend toward better vision in the micropulse-treated eyes.²⁴

While both of these studies were randomized in their design, their results may not be applicable to clinical practice given their small sample size. Multiple other nonrandomized studies have also shown micropulse to be as effective as conventional argon laser.²¹

Vujosevic et al found favorable outcomes on fundus autofluorescence and microperimetry when comparing micropulse laser with conventional laser.¹⁹ Similar results have been found with micropulse laser for the treatment of macular edema in branch RVO.¹

Micropulse may play a role in the treatment of other retinal vascular disorders, including RAMs and CSC. Battaglia Parodi et al found that eyes treated with micropulse laser for symptomatic RAMs had fewer complications than those treated with threshold laser. None of their symptomatic RAM patients treated with micropulse laser developed atrophic scarring around the RAM or a symptomatic epiretinal membrane, compared with 100% and 23% of the RAM patients treated with threshold laser, respectively.²⁵

Despite these findings, all of the treated eyes showed cessation of leakage on FA. Micropulse laser would also be expected to prevent complications, including branch retinal artery occlusion, retinal scarring, and retinal traction.²⁵

Micropulse laser has also been shown to be useful for CSC. At a low duty cycle (5%), micropulse laser has been shown to improve vision, minimize visual field loss, prevent scotoma, and preserve color vision and contrast sensitivity in eyes with CSC,²⁶ without inducing iatrogenic thermal damage.^1,27

Micropulse laser offers a greater safety profile than both conventional laser and photodynamic therapy, which can occasionally cause scotomas, CNV, subretinal fibrosis, RPE atrophy, and choroidal hypoperfusion.¹ Micropulse laser may also provide a precise laser target for more difficult and poorly defined leaking locations in eyes with CSC.¹¹

LIMITATIONS

As with any technology, there are limitations to micropulse laser. The most significant is the lack of standardized treatment parameters, which has been the result of multiple uncontrolled, small, retrospective studies and case series.¹⁹ Laser settings can be different depending on the study, with various duty cycles, spot sizes, and durations being used.²⁰

Depending on one’s point of view, another disadvantage of micropulse laser is its lack of a visible endpoint, which other types of threshold lasers usually provide. Having instant feedback on treatment to reassure the surgeon that the laser was performed properly is not currently possible with micropulse laser.

Use of imaging modalities and functional tests, such as adaptive optics, high-resolution OCT, multifocal electroretinography, and microperimetry, may be able to address this shortcoming in the future. Confirming a therapeutic effect in the absence of measurable data requires a fundamental shift in the practice among vitreoretinal specialists when using micropulse laser.

CONCLUSION

Retinal lasers have come far since their introduction to ophthalmology more than 50 years ago. While newer treatment modalities, such as VEGF inhibitors and steroids, have replaced laser treatment for certain eye diseases as first-line treatments, laser treatment still plays an important role in the management of many retinal diseases.

Pattern and navigated lasers, in general, have made some of the technical aspects of laser safer and more efficient, while placing greater emphasis on patient selection and preparation. Micropulse lasers have minimized collateral retinal thermal damage compared to conventional focal laser, while in some cases maintaining a therapeutic effect.

These newer laser features require more experimentation to determine not only their advantages over older laser treatment modalities but also to establish their place among current pharmaceutical treatments. Further research in this realm will be the driving force for advances in technology to meet our expectations of optimal patient care. RP

REFERENCES