New Approaches to Retinal Laser Therapy

Lasers are an essential tool in treating retinal disease but still fall short of their full potential. We describe innovations we hope to see in the future.

SEENU M. HARIPRASAD, MD ∙ MICHAEL D. OBER, MD

Over more than a half century, laser technology has evolved to become an essential tool in treating vitreoretinal diseases such as diabetic retinopathy, age-related macular degeneration, vascular occlusions, retinal tears and other conditions.

In the January 2009 Retinal Physician, we guided you on a tour of retinal laser history, beginning with the work of Gerhard (Gerd) Meyer-Schwickerath,¹ who led the charge with his 1949 discovery that natural sunlight could be used to perform retinal coagulation. This breakthrough led to treatment with the carbon arc lamp and xenon arc lamp. The introduction of the ruby laser in 1960 ushered in the laser era. Lasers with a range of wavelengths and pulse durations provided greater versatility and precision in treating vitreoretinal disease.

As laser technology advanced, photocoagulation came into widespread use, guided by results from landmark clinical trials. These included the Diabetic Retinopathy Study (DRS),^2,3 which showed that panretinal photocoagulation reduced the risk of severe vision loss by at least 50% in patients with diabetic retinopathy, and Early Treatment Diabetic Retinopathy Study (ETDRS),^4-7 which reported that the risk of persistent macular edema and significant visual loss decreased by approximately 50% in eyes treated with focal laser photocoagulation. In 2008, the Diabetic Retinopathy Clinical Research Network confirmed the benefits of focal laser photocoagulation compared with intravitreal triamcinolone in patients with diabetic macular edema with foveal involvement.⁸

RECENT AND FUTURE ADVANCES

Advances in laser technology are progressing steadily. Until recently, one limitation of retinal lasers was that we could not apply laser spots in a pattern in the periphery of the retina. Therefore, panretinal photocoagulation was a tedious process and it was difficult to individually place 1200 to 2000 burns in the peripheral retina. Although our lasers had a repeat mode, enabling rapid-fire placement of spots, every burn needs to be placed in the peripheral retina with appropriate spacing.

The introduction of the Pascal (pattern scan laser) photocoagulator in 2006 by OptiMedica of Santa Clara, Calif. revolutionized this process. The 532-nm laser applies a uniform pattern of as many as 56 spots in 0.6 seconds. OptiMedica explains that the platform's pattern-specific controls allow clinicians to customize patterns to retinal disease states and anatomic features. With this technology, we can nicely space spots with a consistent retina burn. We can treat more quickly and with greater accuracy, which we hope will produce better outcomes.

Ellex Medical Lasers (Atlanta) is conducting clinical trials of its subthreshold laser system, Retina Regeneration Therapy (Ellex 2RT) for diabetic maculopathy. In November 2008, the company reported six-month data. In a clinical trial of 38 eyes with diabetic maculopathy in England, the system was used to deliver a modified macular grid. Six months after treatment, central macular thickness decreased more than 5% in 46% of patients, whereas it remained stable in 39% of patients and increased more than 5% in 15% of patients. The amount of hard exudates also decreased in more than half of eyes treated. LogMar visual acuity improved by two or more lines in 43% of eyes at six months and one to two lines in 28%. Visual acuity remained stable in 15% and worsened in 14%. Ellex also began clinical trials in Australia.

Although great strides have been made in retinal laser technology over the last 60 years and current treatments are very good, shortcomings persist. We look to the future for next-generation technology that we hope will further improve safety, accuracy and outcomes.

A new laser platform called Navilas (navigated laser) being developed by OD-OS, Inc. of Teltow, Germany offers a number of potential advances.

This laser system, a 532-nm pattern-type retinal laser photocoagulator with integrated digital fundus imaging capabilities, provides all common imaging modalities for the retina (live color fundus imaging, red-free and infra-red imaging, and fluorescein angiography). The manufacturer — a spin-off of a leading eye tracking and registration technology provider for most refractive laser systems — recently developed a retina navigation technology allowing registered overlay of diagnostic images and treatment plans onto the live image of the retina during treatment. This provides the retina surgeon with a retinal laser photocoagulator with a platform to “image, plan and treat” in one system.

Data presented at the ARVO and the Euretina meeting in 2009 by William Freeman, MD, and Aljoscha Neubauer, MD, verifying initial prototypes of the Navilas, suggest that a new level of accuracy for retina treatment may be available with the Navilas system. In the study, 98 eyes were tested with Navilas by several retina specialists at two centers. Of these eyes, 16 eyes subsequently were treated with the Navilas. An average image overlay accuracy of better than 60 microns was obtained, while the overlay could be positioned in more than 95% of all images acquired. Manual positioning of an individual laser pulse in performance tests is accurate within an average of 21 microns at a 50-micron laser spot size. When using rectangular grid patterns, the average positioning error was less than 6% of the spot diameter.

NAVIGATED LASER THERAPY

Navilas allows clinicians to use the device to image the retina with fluorescein angiograms, which then can be used to plan areas to be treated with precise marking of laser pulses or customized patterns, as well as with markings for areas that should not be exposed to the laser beam (Figures 1 and 2). Subsequently, the treatment plan and angiography image can be overlaid onto the live digital fundus image during treatment with the retinal photocoagulation laser. The physician fully controls the application of each preplanned laser pulse, while the Navilas system assists with positioning the laser beam. Furthermore, the platform allows for digital documentation of treatment for future reference.

Figure 1. Screen shot of Navilas planning stage. Note the blockage zones placed over optic nerve and foveal avascular zone. Additionally, note small circles that designate areas of intended treatment placed during planning phase.

Figure 2. Screen shot of Navilas treatment stage. Note overlay of fluorescein angiogram over live color fundus image with registration and tracking features enabled. White dots designate completed treatment, and yellow dots designate planned treatment.

How might this technology improve the surgical experience, specifically as compared to our current capabilities? Below are several likely benefits. Note at the outset that rigorous clinical trials will be needed to prove the safety and suitability of this approach. Consider the information below to be speculative and anticipatory for the time being.

• Clear-Cut Guidance. As we view the retina at the slit lamp during laser treatments, we rely on a number of different imaging modalities to guide treatment. Although fluorescein angiography helps us differentiate the primary abnormalities we will treat, such as microaneurysms and areas of neovascularization, and avoid areas where capillary perfusion is poor, occasionally we cannot see these abnormalities because we are performing laser treatments at the slit lamp. A red dot on the retina might be a microaneurysm, hemorrhage or choroidal neovascular membrane. Therefore, we need to look back and forth between the slit lamp and angiogram image in our medical chart, memorizing the location of these abnormalities by locating surrounding reference points. Navilas integrates different imaging modalities and treatment into one device and provides the means for registered overlay of different imaging modalities to guide us efficiently and precisely during treatments.

In addition, as we view the retina during treatment, we would like to visualize the patient's eye as we are used to seeing it on diagnostic images with a 30- to 50-degree field of view, but live on a large digital computer display rather than as a tiny, inverted, reversed slit image as we currently see it at the slit lamp.

• Protection of Vital Structures. Laser treatment can very effectively treat abnormalities, but the same laser beam can be dangerous to certain vital structures in the eye, such as the optic nerve and foveal avascular zone. Therefore, we obviously want to avoid these areas. Unfortunately, no matter how careful we are, there is always the risk that we may accidentally burn these structures if the eye moves or we don't read the fluorescein angiography properly. The ability to block vital structures from application of laser energy is anticipated to be a key part of the Navilas platform.

• Eye Tracking. Retinal laser treatments demand pinpoint precision. The slightest movement of the eye or lens can necessitate additional burns if you miss the targeted location or may cause potential unnecessary damage. Refractive laser technology has addressed the similar problem with incorporation of advanced eye tracking and registration solutions. We would like future retinal lasers to also incorporate this kind of technology so the laser beam can be stabilized on the retina even as the eye moves. We believe such assistance in targeting the laser beam may improve accuracy in retinal laser treatments, and we would be able to study whether this would improve outcomes and safety. Increased accuracy also may allow us to treat effectively with less power, although that remains to be determined in clinical trials.

• Digital Documentation. Accurate documentation is also critical after retinal laser surgery, and current systems lack this capability. Retina surgeons often need to rely on their artistic abilities to sketch a picture of the retina and treatment location into a patient's chart, accompanied by notes on the number of spots, power used, and intensity of each burn. Current systems don't allow us to image the eye after the procedure so we know exactly where the treatment was performed.

We hope future laser technology used in the Navilas platform (and perhaps others) will provide fundus photographs showing the precise location of laser burns. Not only could we use these photos to plan subsequent treatments, we would be able to monitor the effect of such localized treatment on future diagnostic images. We also would be able to show patients their photos when explaining treatments and use photos for medico-legal documentation after procedures. Furthermore, we could send photos to a patient's referring ophthalmologist, demonstrating the treatment we performed.

• Consistent Applications. We participate in clinical trials for diabetic macular edema and diabetic retinopathy, which carry strict protocols for treatment. However, we also know treatment techniques vary among surgeons, depending on how they focus the laser on the retina and the machine or lens the surgeon uses. We hope future technology will provide objective tools allowing us to quantify and standardize treatments between lasers. This would provide an objective, quantifiable approach to laser treatment that may be better suited to clinical trials using retinal laser treatment.

• Feeder Vessel Treatment. In addition, as retinal treatments become more accurate, we hope to be able to effectively treat the blood vessels that feed the neovascular membrane in patients with age-related macular degeneration. In this way we hope to block the blood supply from reaching the membrane and shut down the disease process. If we could overlay a fluorescein angiogram or indocyanine green angiogram over the fundus image to precisely target treatment, it would allow us to perform feeder vessel treatments for retinal angiomatous proliferative lesions. This is theoretically possible with the Navilas laser and hopefully a future application of the technology.

ON THE HORIZON

We are excited to see that navigation, which has been successfully established in other medical fields like neurosurgery and urology, is making inroads into retina treatment. We foresee a bright future in the development of retina laser technology. Future evaluation will determine how these benefits improve clinical outcomes. We have described our wish list of future features and we hope these advances someday improve safety, accuracy and, ultimately, outcomes. RP

REFERENCES

1. Meyer-Schwickerath G. Light coagulation. St. Louis.MO: CV Mosby; 1960.
2. The Diabetic Retinopathy Study Research Group. Preliminary report on the effect of photocoagulation therapy. Am J Ophthalmol. 1976;81:383-396.
3. The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings. DRS Report Number 8. Ophthalmology. 1981 ;88: 583-600.
4. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for Diabetic Macular Edema: ETDRS Report Number 1. Arch Ophthalmol. 1985: 103:1796-1806.
5. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for Diabetic Macular Edema: ETDRS Report Number 4. Int Ophthalmol Clin. 1987;27:265-272.
6. Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy: ETDRS Report Number 8. Ophthalmology. 1991;98:757-765.
7. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS Report Number 9. Ophthalmology. 1991 98:766-785.
8. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravltreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115:1447-1449.