Glaucoma experts give perspectives on LiGHT trial: SLT vs. drops

Earlier this year, The Lancet published the results of the LiGHT trial, comparing selective laser trabeculoplasty and eye drops to treat patients with open-angle glaucoma, which found SLT provided more robust IOP lowering while being a more cost-efficient first-line treatment.

Of 718 patients enrolled in the observer-masked, randomized controlled trial, 356 were treated with SLT and 362 were treated with eye drops. Researchers reported 91% of patients in the study returned the primary outcome questionnaire regarding health-related quality of life at 3 years assessed by EQ-5D scores.

At 36 months, the average EQ-5D score for the SLT group was 0.89 compared with 0.90 in the eye drop group, which was not a statistically significant difference. The groups had similar endpoint visual acuity, IOP and visual field loss mean deviation as well.

Source: Shari Fleming Photography

Overall, 95% percent of eyes in the SLT group, with and without IOP-lowering medication, were at target IOP at 36 months, while 93.1% of eyes in the eye drop group were at target IOP. No SLT patients required glaucoma surgery to lower IOP compared with 11 patients who required surgery in the eye drop group.

Use of SLT as first-line treatment resulted in reduced cost of surgery as well as for medications, with an overall cost saving to the National Health Service of 451 pounds per patient in specialist ophthalmology costs.

“Our data support a change in practice; however, clinicians will need to consider patients’ perceptions of the necessity of monitoring visits, in the absence of daily medication. Primary selective laser trabeculoplasty is a cost-effective alternative to drops that can be offered to patients with OAG or ocular hypertension needing treatment to lower intraocular pressure,” the researchers wrote in the study.

Ocular Surgery News spoke with seven glaucoma surgery experts who shared their opinions on the study, its results and their opinions on what first-line treatments should be used for open-angle glaucoma.

Thomas W. Samuelson, MD, OSN Glaucoma Section Editor

Disruptive studies that alter conventional, and for some nearly automated, clinical practice patterns tend to be few and far between in medicine. The LiGHT trial is one such study. Impeccable in its design and execution, LiGHT utilizes consensus guidelines from the world’s most respected glaucoma organizations to help guide glaucoma staging, severity and treatment escalation to effectively compare SLT and drop therapy for the initial treatment of glaucoma. The results of this trial should challenge clinicians to reassess their approach to clinical practice. Indeed, this trial is worthy of careful consideration.

When assessing the efficacy of any therapy, it is first essential to contextualize the population under study. Patients in this study had primarily mild disease. Indeed, nearly one-third of patients in each group had no disease but rather ocular hypertension with enough risk to require treatment. Half of the patients in each arm had mild POAG. The remainder of the study cohort had moderate (11% to 12%) or severe (5% to 6%) glaucoma. Notably, with a mean deviation of –3.2 dB in each arm, glaucoma severity in this study was strikingly similar to the FDA premarket approval MIGS trials.

Briefly, the authors randomly assigned patients naive to glaucoma therapy to receive either SLT or a standardized regimen of eye drops. Laser treatment consisted of 360° treatments. The power ranged from 0.3 mJ to 1.4 mJ, determined by surgeon discretion. Treatment consisted of 25 pulses per quadrant, 100 pulses per treatment. One laser re-treatment was allowed before moving on to medical therapy. The second arm of the study involved stepped eye drop therapy consisting of a prostaglandin, followed by a beta-blocker and then either an alpha-2 agonist or topical carbonic anhydrase inhibitor, escalating until target IOP was reached.

Seventy-eight percent of the laser-first eyes were controlled at 36 months; of those, 77% required just one treatment. Laser-treated patients were at target IOP for 93% of visits over 3 years compared with 91% for the eye drop group. Only one patient experienced a post-laser IOP spike that required treatment, and overall, the laser-first group had excellent safety data.

Eleven eyes in the eye drop group required trabeculectomy to lower IOP compared with none in the SLT group. Moreover, cataract surgery was required more frequently in the medication group, raising the question that glaucoma medications might hasten cataract formation.

In summary, compared with eye drop therapy, laser-first treatment was safe, was more cost-effective, was equally or more efficacious, resulted in fewer subsequent trabeculectomies and cataract surgeries, and was less reliant on patient compliance. While previous studies have shown laser first to be equal to single drop therapy, none have had the veracity of the LiGHT trial. This is the most definitive study to date suggesting that laser first is not only a viable option for initial glaucoma therapy, it appears to be superior first-line therapy.

Malik Y. Kahook, MD, OSN Glaucoma Board Member

The recent study by Gazzard and colleagues in The Lancet has sparked a great deal of discussion within our glaucoma service at the University of Colorado. We chose this article for discussion at a recent journal club, and the ensuing discussion ranged from strong cautionary statements to avoid overgeneralization of the data to others advocating for a big shift toward a more vigorous offering of laser trabeculoplasty as primary therapy for all newly diagnosed glaucoma patients.

Currently, I offer SLT as primary therapy to all patients with open-angle glaucoma. I also discuss all the medical options, and then I step back to allow the patient to think through the options and choose which is most compatible with their personal needs and beliefs. Often, patients choose a single prostaglandin analogue drop per day over laser therapy, and I have been comfortable with this choice, as have most of my glaucoma colleagues around the globe. It can be argued that the language we use when presenting laser vs. medications might bias patients toward medications. It can also be argued that the simple use of the word “laser” might induce a level of fear that makes the lay patient choose medications as a less invasive option.

The study by Gazzard and colleagues adds a great deal of knowledge that can inform my discussions, having been conducted in treatment-naive patients, which more closely mimics the scenario when I initially present SLT as an option to my patients. In the past, we mostly relied on anecdotal data or data sets that were not from treatment-naive patients. Still, it should be noted that some of the inclusion and exclusion criteria, such as disease type and baseline testing values, may not apply to a significant portion of patients in some practices.

The ability to re-treat with SLT after only 8 weeks when the first treatment was not successful in the LiGHT study is also not standard practice and may present follow-up difficulties from a monitoring standpoint.

Overall, we should consider SLT more frequently when initiating treatment in glaucoma and ocular hypertension patients. My narrative when discussing options for the initiation of glaucoma therapy can now be augmented with these data.

Steven J. Gedde, MD, OSN Glaucoma Board Member

The investigators are to be congratulated for conducting a landmark clinical trial that has the potential to create a paradigm shift in glaucoma management. It found that SLT was a highly effective, safe and cost-effective treatment for OAG and ocular hypertension. That has important implications worldwide, not only for third-world countries where there is limited access to medical therapy, but also for developed nations such as the U.S., where there is a growing emphasis on value-based medicine.

The Glaucoma Laser Trial (GLT) was another landmark study that compared argon laser trabeculoplasty vs. medical therapy using a stepped regimen as first-line treatment for newly diagnosed primary open-angle glaucoma. Each eye was randomly assigned to either ALT or medical therapy starting with timolol.

Timolol frequently has a contralateral IOP-lowering effect, which potentially biased the results in favor of laser treatment. That was a design flaw, but it is still an important trial that demonstrated ALT is a safe and effective initial therapy for glaucoma.

Despite providing high-level evidence supporting the use of ALT as a first-line therapy for glaucoma, the GLT did not have a large impact on clinical practice. A survey of members of the American Glaucoma Society shortly after the 2-year results of the GLT were published showed that few glaucoma specialists were using ALT with any regularity as an initial therapy for OAG.

The LiGHT trial will likely be more impactful, considering the trial’s excellent design and execution, and an expanded experience with laser trabeculoplasty to manage glaucoma.

L. Jay Katz, MD, and colleagues performed a study randomizing patients to SLT vs. medical therapy in a stepped regimen usually beginning with a prostaglandin analogue. It was a smaller trial, so it was not as well powered to detect differences between the two randomized treatment groups. It was nevertheless an important contribution to the medical literature.

There is no question that LiGHT is a high-quality trial with the potential to have a huge impact on clinical practice. We are excited about the results, but it is noteworthy that there was not a statistically significant difference in the primary outcome measures between the two treatment groups.

It did, however, demonstrate that there was a cost benefit in initial treatment with SLT, and cost is certainly an important consideration in health care delivery. I found it surprising how effective SLT was as an initial therapy, probably related to the fact that it was performed in treatment-naive patients. Historically, SLT has been used as an adjunct to maximum tolerated medical therapy to gain additional pressure reduction. It is perhaps not surprising that SLT is less effective in that setting.

The other traditional niche for SLT has been in patients who are poorly compliant or poorly tolerant to medical therapy. But results from the LiGHT trial highlight the value of SLT as initial therapy for all patients with OAG and ocular hypertension.

Not all forms of glaucoma are amenable to laser trabeculoplasty, including angle-closure glaucoma and certain types of OAG (eg, glaucoma associated with elevated episcleral venous pressure). But for most patients with OAG, I routinely offer medical therapy and SLT as viable initial treatments.

A majority of patients elect initial medical therapy, finding comfort in the idea of starting with a less invasive treatment, even though laser trabeculoplasty is minimally invasive and safe.

It is important to practice evidence-based medicine when caring for patients. Sharing high-quality information with patients helps guide the discussion and choice of treatment. Already, I have incorporated the results of the LiGHT trial in managing patients with newly diagnosed OAG.

Robert J. Noecker, MD, MBA, Ophthalmic Consultants of Connecticut

The LiGHT trial is a large, fairly well-done study. We have a lot of confidence in the results because, if nothing else, they are consistent and supportive of the data. There have been smaller retrospective and prospective studies that have looked at similar questions, but the LiGHT trial is consistent and has confirmed what other studies suggested.

I am a bit biased because I was an original SLT investigator for FDA approval. I have been doing it for 20 years and always embraced it as appropriate as first-line therapy. In the original FDA trial, patients were not treatment-naive: Either maximum therapy had failed, or prior laser trabeculoplasty had failed. Those treatment groups are arguably the populations in which laser trabeculoplasty is least successful.

The LiGHT trial has sparked discussion and reevaluation of practice patterns. If I had glaucoma, I would have SLT first. Then I would add a prostaglandin analogue as second therapy if needed. I wish more practitioners would do this. It is good for the patients and good for the doctors. Again, I am biased because I have been doing this for a long time.

That said, in the real world, the glaucoma therapy options are not mutually exclusive. Each patient deserves customized therapy.

As providers, the way we present the options indicates our acceptance or confidence in the therapy. I tell my patients to expect having both laser and medications, whatever it takes to get the eye pressure down.

Nathan M. Radcliffe, MD, clinical associate professor of ophthalmology at New York Eye and Ear Infirmary and cataract and glaucoma surgeon at New York Eye Surgery Center

One finding I believe to be the gem of the study is that 11 patients in the eye drop arm went on to need glaucoma surgery, while none of the patients in the laser arm required surgery.

It is not the case that no laser patients will ever need glaucoma surgery, but this tells us something about the likelihood of disease worsening to the point of having surgery. It shows that laser can go a long way to mitigating that risk.

Keep in mind, this is early glaucoma and ocular hypertension, so it is surprising that 11 of 362 patients even went on to need surgery. But glaucoma can progress quickly, and laser makes a difference particularly when done early.

One theory is that laser done early in disease rejuvenates the outflow system, creating a positive feedback loop in terms of lowering pressure, whereas aqueous suppressants decrease fluid production, thus decreasing trabecular meshwork function and creating a negative feedback loop.

From a practical standpoint, I am an advocate of laser first for POAG or ocular hypertension. I offer it to all patients for their first step. I also use the laser for any patient on drops who is experiencing side effects, a lack of efficacy or other tolerability problems. In addition, I use laser for patients who are having trouble affording their glaucoma drops or having problems with compliance.

Bottom line is that this study clearly shows laser is not just an acceptable first-line therapy for ocular hypertension or glaucoma but is the preferred first-line therapy. Laser itself may be better implicated earlier in the disease rather than late in the disease where it is used now. This should save payers and patients money.

Laser, which is generally approved by insurances, is associated with fewer administrative problems such as making pharmacy callbacks for drugs that have poor coverage or other formulary problems. Our employees are freer to focus on other aspects of excellent patient care.

Douglas J. Rhee, MD, OSN Glaucoma Board Member

There are no surprises here. There have been three other trials of admittedly shorter duration with similar results. These studies show SLT is at least as good as topical prostaglandin at the start of treatment for glaucoma. I believe the LiGHT trial, going further out than the others, showed additional benefits over drug therapy, including being more cost-effective.

It has been shown repeatedly that laser is at least as good as drug therapy, if not more beneficial, with regard to compliance, cost and, of course, side effects. There are clear advantages outside of IOP-lowering efficacy.

But the body of literature, including the LiGHT trial, has not changed practice. I don’t think that clinical evidence is enough to change practice here. Part of it is patient acceptance and perception, which is why it has not changed my practice to any large degree. I still start with medication. Even though I offer laser, when I mention the therapy, the patient kind of gently recoils. Then when I suggest medication, they relax. I don’t think any of us are trying to convince our patients to do anything they are not comfortable with. The vast majority of my patients choose to start with medications.

Some practitioners will introduce laser treatment earlier in the regimen. Instead of offering it after exhausting all the different topical medications, they may try it after two or three medications.

I don’t think the LiGHT trial is going to make much more difference. There is a slow trajectory of offering laser even earlier in the treatment regimen. Outside of some other major economic changes, I am not sure laser will be utilized first line for a while longer. The main driver for me in my practice is patient acceptance.

Savak “Sev” Teymoorian, MD, MBA, OSN Glaucoma Board Member

The climate in glaucoma has been shifting with newer technology, including pharmacological and surgical interventions. Instead of waiting for damage to the optic nerve and functional visional loss, we have better ways of addressing pathology when it comes to our patients. Instead of waiting for issues, we are more aggressive with treatment. With the advent of newer medication and surgical intervention, we continue to push that envelope to be more proactive. We do this for quality of life because we want to make sure all our patients are seeing well at the end of life. We did not have great options before, but now we do.

I am happy to see there is a shift in the treatment paradigm for glaucoma. This goes in line with SLT and the way we incorporate it into our intervention and treatment for patients. At first it can be difficult when you bring up laser therapy to an overwhelmed patient. They have just been diagnosed, and they can be hesitant to undergo laser therapy. Many want to revert to using medication. But patients are becoming more aware of different technologies and better ways to treat glaucoma, and they want a better quality of life. This can make them more accepting of other therapies to reach their goals.

I previously used SLT throughout the spectrum of glaucoma, but now I am using it earlier as a first-line therapy if the patient is the right one to consider. I am glad to see the published results were consistent with this strategy.

The goal is to bring IOP down at all time points and for all patients to have a good quality of life. We bring IOP down so there is no damage to the optic nerve. This helps patients maintain good functional vision and lets them do the activities they want to do.

One of the difficulties of treating glaucoma patients with eye drops is the issue of noncompliance and nonadherence. This is a multifactorial problem with the same end result: The patient is unable to get the drops into their eye. The best way to solve this is to remove the responsibility from the patient and put the responsibility onto the doctor. SLT solves this as a first-line treatment, and I am excited to see that we are shifting the way we are thinking about how to take care of our patients and manage this disease in a better way.

Almost every patient is a good SLT candidate, apart from a patient with inflammatory glaucoma. If the angle anatomy gives you a good view of the anatomical site, they should be a good candidate.

Interestingly, before the study was published, I was speaking at a conference where we presented a patient study to a group of ophthalmologists. We asked the ophthalmologists what their first-line treatment would be for early glaucoma, eye drops or laser. About 90% said they would start with eye drops. We then changed the question and asked the ophthalmologists how they would want their own early glaucoma treated. About 90% said they would do laser on themselves. There is a disconnect on what we would do for a patient vs. what we would do for ourselves.

Patients are not familiar with the laser procedure. I explain it to patients by saying we provide a light therapy to the eye. It is just like getting a tan in your eye; your body absorbs the light energy, and as a reaction, your body cleans the natural drainage system of the eye first. Your body does the work, but you just need a signal first.

But if the doctor does not explain what the laser is, I can see why patients would be shy and would want to try drops first. It is a matter of physicians finding a way to educate their patients.

• Reference:
• Gazzard G, et al. Lancet. 2019;doi:10.1016/S0140-6736(18)32213-X.

• For more information:
• Steven J. Gedde, MD, can be reached at Bascom Palmer Eye Institute, 900 NW 17th St., Miami, FL 33136; email: sgedde@med.miami.edu.
• Malik Y. Kahook, MD, can be reached at University of Colorado, Anschutz Medical Campus, Department of Ophthalmology, 1675 Aurora Court, Aurora, CO 80045; email: malik.kahook@ucdenver.edu.
• Robert J. Noecker, MD, MBA, can be reached at Ophthalmic Consultants of Connecticut, 1375 Kings Highway, Fairfield, CT 06824; email: noeckerrj@gmail.com.
• Nathan M. Radcliffe, MD, can be reached at New York Eye Surgery Center, 1101 Pelham Parkway North, Bronx, NY 10469; email: drradcliffe@gmail.com.
• Douglas J. Rhee, MD, can be reached at Department of Ophthalmology and Visual Sciences, Case Western Reserve University School of Medicine, Euclid Ave., Mail Stop WRN5068, UHI Institute, Cleveland, OH 44106; email: dougrhee@aol.com.
• Thomas W. Samuelson, MD, can be reached at Minnesota Eye Consultants, 710 E. 24th St., Suite 100, Minneapolis, MN 55404; email: twsamuelson@mneye.com.
• Savak “Sev” Teymoorian, MD, MBA, can be reached at Harvard Eye Associates, 24401 Calle De La Louisa, Suite 300, Laguna Hills, CA 92653; email: steymoorian@harvardeye.com.

Disclosures: Gedde reports no relevant financial disclosures. Kahook reports no relevant financial disclosures. Noecker reports he is a consultant to Ellex, Iridex and Quantel Medical. Radcliffe reports no relevant financial disclosures. Rhee reports he is on the speakers bureau for Aerie Pharmaceuticals, Ivantis and Bausch + Lomb; receives research grants from Allergan, Glaukos and Ivantis; is on the data safety monitoring board for Ocular Therapeutix; and is an ad hoc consultant for Alcon, Allergan, Aerie Pharmaceuticals, Bausch + Lomb and Ivantis. Samuelson reports no relevant financial disclosures. Teymoorian reports he is a consultant and speaker for Ellex.