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Laser as first line therapy could change paradigm of treatment for glaucoma
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The results of a 3-year trial recently published in The Lancet provide compelling evidence that selective laser trabeculoplasty performed as a first-line treatment in newly diagnosed cases of glaucoma and ocular hypertension provides better control of IOP at a lower cost and with fewer side effects compared with medications. These findings caused a stir among glaucoma specialists and the ophthalmology community at large and may bring about a paradigm shift in the approach to glaucoma treatment.
“My personal view is that this study will transform policies and transform the initial treatment of glaucoma for all patients around the world,” Gus Gazzard, MD, FRCOphth, first author of the study, said. “The news is spreading fast, and a lot of colleagues are already switching to laser as first-line treatment.”
SLT has been around as a technique for more than 20 years but had never gained wide acceptance and was mainly used as an adjunctive therapy in eyes already treated with medications. This study is the first to provide robust evidence, and therefore a rationale, to use SLT before and without medications in newly diagnosed glaucoma eyes.
Source: Gus Gazzard, MD, FRCOphth
The trial
The Laser in Glaucoma and Ocular Hypertension (LiGHT) study was an observer-masked, randomized controlled trial conducted at Moorfields Eye Hospital and five other hospitals across the United Kingdom; 1,235 eyes of 718 patients with newly diagnosed untreated open-angle glaucoma or ocular hypertension were identified and randomly assigned to treatment with either SLT or medications. Disease severity and baseline IOP were used to set individual pressure targets, treatment intensity and monitoring intervals. SLT was delivered to 360° of the trabecular meshwork, 25 shots per quadrant, with energy varying between 0.3 mJ and 1.4 mJ. In the medical therapy group, prostaglandin analogues were used as first-line treatment.
Precise treatment escalation criteria were established, following international guidelines of the European Glaucoma Society, the American Academy of Ophthalmology Preferred Practice Pattern and the South East Asia Glaucoma Interest Group. One re-treatment with SLT was allowed if the first treatment had shown efficacy. The next escalation was medical therapy, while surgery was offered after maximum tolerated medical therapy.
At 3 years, 78.2% of the eyes treated with SLT were at target pressure without medications. Of these, three-quarters required only one laser treatment. Disease progression occurred less frequently than in the eye drops group, 23 eyes vs. 33 eyes. While 11 eyes in the eye drops group required trabeculectomy due to uncontrolled IOP and/or visual field progression, the same did not occur in any of the eyes in the SLT group.
Cataract also occurred more frequently with eye drops, 25 eyes vs. 13 eyes, supporting existing evidence that the topical medications used to treat glaucoma may accelerate cataract formation, according to the authors.
The side effects of SLT, including discomfort, blurred vision, hyperemia and photophobia, were mild and transient.
Results beyond expectations
“Results were better than we expected. We were very excited about the magnitude and also the duration of the pressure reduction,” Gazzard said. “SLT showed a greater ability to reduce IOP when used in naive eyes and the ability to postpone the use of medications for at least 3 years in a high number of patients.”
In the follow-up study, currently ongoing, many of the patients are still controlled at 5 or 6 years, he said.
One of the reasons why SLT showed superior efficacy compared with eye drops is because it overcomes the well-known problems of compliance and adherence to medical treatment. SLT may also provide better stability than drops due to its continuous effect on the trabecular meshwork.
“I do not think that laser will replace drops entirely, but the need for drops can be postponed by several years. Medications have adverse effects, and patients are more comfortable without them. In addition, if surgery is needed, it will be more successful because eye drops may affect the outcome of future surgical interventions,” Gazzard said.
The use of SLT as first-line treatment was shown to be highly cost-effective, with an overall cost saving to the NHS of 451 pounds in direct treatment costs per patient.
“The data that we used for this study were the real usage data that we collected from our own institutions. We did not base cost-effectiveness on assumption but on real-world genuine hard numbers, so it is very robust data and very promising,” Gazzard said. “We’ll see if the National Institute for Health and Care Excellence, after reviewing the study, will change the current recommendations on glaucoma treatment.”
Accessibility to treatment
The study mirrored clinical practice by including patients of different ethnic origins and degrees of glaucoma severity and by tailoring pressure targets and treatment schedules to the individual patient. At the same time, it followed a well-defined protocol for randomization, follow-up and analysis of data.
“As a member of the community of glaucoma clinicians, I am very impressed with this study. It was very large, with a wide range of glaucoma severity and types, and results are therefore well generalizable to the wider population. It is a landmark glaucoma trial, a major piece of work,” Augusto Azuara-Blanco, PhD, FRCS(Ed), FRCOphth, said.
He expects significant changes in clinical practice following this study, not only because SLT is more cost-effective for health care providers, but also because it is safe and easy to deliver. The skills required can make it suitable for the general ophthalmologist.
“The advantage will be even greater for the developing world and low-income countries, where medical treatment is not accessible because costs are too high. The possibility of doing laser treatment in these areas of the world is going to have a major impact in reducing glaucoma-related blindness globally,” Azuara-Blanco said.
A new awakening
Dale K. Heuer, MD, president of the American Glaucoma Society, congratulated the authors for the “extraordinarily well-designed study.”
“It is thoughtfully and methodically designed in every respect, and particularly the way they systematized the escalation of therapy was just remarkable. It really answers the question, is SLT safe? Is it effective compared to the usual clinical standard?” he said.
A number of studies had partly shown that SLT was safe and effective, and the AAO Preferred Practice Pattern and technology assessment both indicate that trabeculoplasty should be considered for initial treatment. Yet, the majority of U.S. general ophthalmologists and glaucoma specialists start with medications and reserve laser for later, after eye drops have partially failed.
“The data from the LiGHT study tell us in a very compelling way that we are probably doing our patients a disservice if we don’t let them know how good laser could be and that it is an alternative option to medications,” Heuer said.
When the Glaucoma Laser Trial findings were presented at the American Academy of Ophthalmology meeting 20 years ago, showing that argon laser trabeculoplasty worked as well or better than timolol, reactions were tepid.
“At the time, I was surprised that half of the audience didn’t get up and march out to one of the laser companies to buy a laser,” he said. “It is hard to change the way physicians approach things. We tend to be slow at changing from the approaches that we learned during our training.”
Although it is difficult to translate the cost-effectiveness data of the LiGHT study into the U.S. health care system, the cost-saving value of SLT compared with eye drops is self-evident, according to Heuer.
“Considering that by 3 years three-quarters of the patients did not need any medicines, SLT should be very competitive with even generic medications,” he said. “I have only half-kiddingly said from a podium approximately 20 years ago that if I were a health care system medical director, if all costs were considered, I would mandate that SLT be done first.”
Long-term medication use is also primarily associated with numerous issues of poor adherence, difficulty of administration, difficulty with monitoring the treatment and erratic availability in U.S. pharmacies, particularly for dorzolamide. Laser is “one and done,” and results are easier to predict and monitor, Heuer said.
General shift toward procedures
As an early advocate and user of SLT, Robert J. Noecker, MD, MBA, was happy to see this study confirm what he does already in his practice.
“When I offer SLT to my patients, I don’t confuse them with a difficult ‘either/or’ choice, but rather tell them that the initial treatment is laser ‘and’ medications. I say, ‘We do laser first, and when you come back in 6 weeks, we will measure how good it is. If we have reached our goal, we’ll stop there. If we have not, we’ll add on a drop.’ I don’t make it an ‘or’ but an ‘and’ proposition, so if we don’t go the next step, the patients are happy, and if we have to add medications, they are not surprised,” he said.
In most cases, he said, no additional medications are needed if SLT is performed at the early stages.
“I look at SLT as the most benign therapy that we have, and if I had glaucoma, I would have done it for me because problems are low and efficacy is quite high,” Noecker said.
The choice of using SLT as first-line therapy made Noecker an outlier 10 years ago, but trends are slowly changing and physicians now feel more comfortable with the procedure. Due to the increasing cost of medications and the issues of availability, compliance and adherence, there has been a general movement toward procedures as potentially better alternatives, both with MIGS in the OR and laser in the office.
The increasingly high cost of medications has made coverage of prescription drugs unstable in the past few years. As a result, it has become difficult for doctors to ascertain that patients continue the treatment the way they prescribed.
“I prescribe branded medications because we have more data and results are more predictable, but at the pharmacy level, they might get substituted with a generic equivalent. Formularies change every year, and the drops one patient has been using for many years may no longer be covered at some point, and quite unpredictably,” Noecker said.
“With laser, we know what the treatment is, and we don’t have to deal with unpredictable changes that force us to move from bimatoprost to latanoprost the next time because the first is no longer covered. With SLT, predictability is not perfect, but I know what my patients are going to get and the cost is lower overall,” he said.
For these reasons, Noecker sees that the number of colleagues who consider laser as an appropriate initial therapy is already growing. He estimates they may be approaching 50% and that the LiGHT study will give this trend a new and more definite impulse.
“The good thing about this study is that it got people talking and thinking about this again, and I am quite sure we’ll see a push toward SLT becoming first-line therapy in a greater percentage of patients,” he said.
Time to dispel misconceptions
Thomas M. Brunner, MBA, president and CEO of Glaucoma Research Foundation, said he is thrilled about the study and the implications it has for helping patients. The ability to diagnose the disease and treat it at the same time, with the potential of a multi-year benefit, is huge in both developed and developing countries.
“I am thinking of regions like West Africa, where the prevalence of glaucoma is high and will grow even further in future years because life expectancy is going up,” he said.
In these regions, the cost of medications is unaffordable, and regular monitoring of patients is not possible because of long distances.
“There is an initial investment for the equipment, which is expensive, but given the extent of the problem, I see that there is a huge opportunity for cost-effective interventions and optimized resource management,” Brunner said.
He welcomed this paper as a milestone that will change physicians’ attitudes, making them confident in offering SLT as first therapy. It will help dispel the misconception that laser is somewhat threatening while drops are innocuous.
“If SLT is presented as laser surgery and drops as an innocuous therapy, which one would you have? This becomes an issue of terminology,” he said.
Because the term “laser surgery” creates unjustified anxiety, he proposed that SLT should rather be presented as “light therapy.”
“What we are talking about is using a low level of light to stimulate a response in the eye, which will restore the normal aqueous outflow without eye drops and with none of the side effects that drops have,” Brunner said. “We need to educate doctors to present this option to the patients in a different, realistically positive way.” – by Michela Cimberle
- References:
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- For more information:
- Augusto Azuara-Blanco, PhD, FRCS(Ed), FRCOphth, can be reached at Queen’s University Belfast, 2017 University Road, Belfast, BT7 1NN, Northern Ireland, United Kingdom; email: a.azuara-blanco@qub.ac.uk.
- Thomas M. Brunner, MBA, can be reached at Glaucoma Research Foundation, 251 Post St., Suite 600, San Francisco, CA 94108; email: grf@glaucoma.org.
- Gus Gazzard, MD, FRCOphth, can be reached at NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, London, United Kingdom; email: gus.gazzard@moorfields.nhs.uk.
- Dale K. Heuer, MD, can be reached at Medical College of Wisconsin, 25 N. 87th St., Milwaukee, WI 53226-4812; email: dheuer@mcw.edu.
- Robert J. Noecker, MD, MBA, can be reached at Ophthalmic Consultants of Connecticut, 1375 Kings Highway, Fairfield, CT 06824; email: noeckerrj@gmail.com.
Disclosures: Gazzard reports he is a consultant for Alcon, Allergan, Glaukos, Ivantis, Merck/MSD, Santen and Thea. Noecker reports he is a consultant for Ellex and Iridex. Azuara-Blanco, Brunner and Heuer report no relevant financial disclosures.
Click here to read the Point/Counter, “Could SLT represent an affordable and effective solution for glaucoma care in low-income regions?”