Laser Trabeculoplasty Tops Eye Drops as Frontline Treatment for Glaucoma

CHICAGO — Upfront laser trabeculoplasty significantly slowed glaucoma progression and vision loss as compared with eye drops, long-term follow-up from a large randomized trial showed.

After 6 years of follow-up, patients randomized to selective laser trabeculoplasty (SLT) had a 29% lower rate of glaucoma progression versus eye drop therapy. The rate of fast progression was more than twice as high with an eye drops-first strategy, and ultra-fast progression occurred three times as often when patients started treatment with eye drops.

The advantage of SLT over eye drops occurred despite ongoing treatment-to-target of intraocular pressure (IOP) in both randomized groups, reported Giovanni Montesano, MD, PhD, of Moorfields Eye Hospital in London, at the American Academy of Ophthalmology meeting.

“If you achieve a predefined target IOP based on the severity of disease, this probably implies that we need further studies to understand the relationship between IOP control and visual field progression with different types of treatment,” said Montesano. “It’s not just the pressure that matters, the target IOP specifically, but the way we achieve that can make a difference.”

During a discussion that followed the presentation, an unidentified member of the audience asked whether the type of eye drop made a difference, for example, beta blockers versus alpha agonists. Montesano said investigators have the data on the types of eye drops used but have not analyzed it.

“If more patients in one arm were allergic to a specific agent, had a higher frequency of drops that might be neurotoxic or neuroprotective, that shouldn’t matter, looking at the randomization,” said Montesano. “However, it’s something we can definitely look into.”

The same questioner asked whether quality of IOP control over a 24-hour period might have affected the results. Montesano said investigators have not looked at that issue but the data are available.

Another unidentified member of the audience wondered whether IOP is as predictive as assumed and whether it might have been confounded by differences in adherence to eye drops before and after SLT.

“This is one line of [our] thinking,” said Montesano. “It could be that we have a poor estimation of pressure during office hours, which could be either from compliance — and that’s our hunch as the main explanation — or the fact that even when used properly, the drops’ effect might not be the same throughout the day or throughout the night. That can also affect the way the visual field reacts.”

“It is difficult to elucidate from this dataset because we haven’t collected home monitoring measures of IOP, more detailed measurements that would allow us to investigate that,” he added.

Session moderator John Lind, MD, of Indiana University in Indianapolis, noted that investigators focused on mean deviation from the target IOP as the endpoint and pointed out that a number of factors can influence mean deviation, such as cataract.

“Are there any other indices that you could look at, for visual fields, that might correct for that, or other outcomes from visual field testing that could correct for that confounding?” Lind asked.

Montesano said investigators plan to examine average deviation as a means of removing the confounding effect of cataract, “but as far as I can remember, there wasn’t a significant difference between the two arms in terms of cataract.”

Historical Context

Historically, glaucoma and ocular hypertension have been treated with pressure-lowering eye drops. SLT is an alternative but not commonly used as first-line therapy. SLT reduces ocular pressure by means of a single outpatient procedure that increases aqueous outflow through the trabecular meshwork of the eye. Introduced in 1995, SLT received FDA approval in 2001. A systematic review published in 2007 highlighted the need for studies comparing the efficacy and cost-effectiveness of SLT and eye drops for lowering IOP in glaucoma and ocular hypertension.

The randomized, phase III LiGHT trial compared SLT and eye drops as initial therapy for patients with open-angle glaucoma (OAG) or ocular hypertension. Results at 36 months showed no significant difference in health-related quality of life, the primary endpoint. At that point, three-fourths of the patients randomized to SLT had not required eye drops to control IOP.

Also at 3 years, patients in the SLT arm maintained target IOP with fewer clinic visits as compared with patients randomized to eye drops. No patient in the SLT arm required glaucoma surgery versus 11 in the eye drop arm. A cost-effectiveness analysis showed a 97% probability that upfront SLT was cost-effective at a willingness-to-pay threshold of £20,000 (currently $26,000).

Advanced Analytics

Montesano reported findings from 6 years of follow-up in the trial. Eligible patients had newly diagnosed OAG or ocular hypertension. Patients with OAG had visual field loss no greater than -12 dB in the better eye and no greater than -15 dB in the worse eye. Patients with involvement of one or both eyes received identical treatment. The trial involved 718 patients.

Using advanced statistical techniques that employed Bayesian principles to separate median deviation rates from perimetric noise and learning effects, investigators calculated the “true” median deviation rate of visual field progression. The baseline median deviation rate was -2.15 dB in the SLT arm and -2.13 dB in the eye drop arm.

The results showed a 29% difference in the rate of progression in favor of starting treatment with SLT (-0.37 dB/year vs -0.26 dB/year, P=0.006). Using a cutoff of -0.50 dB/year to define fast progression, investigators found that almost twice as many patients who started treatment with eye drops met the definition (25.4% vs 14.4%; OR 2.15, 95% CI 1.22-3.65). With a cutoff of -1 db/year, three times as many patients in the eye drops group had very fast progression (6.5% vs 2.1%; OR 3.80, 95% CI 1.39-9.06).

“Selective laser trabeculoplasty should not only be considered an effective and safe alternative to medications as a first-line treatment for primary open-angle glaucoma, but can also offer an advantage in reducing vision loss,” said Montesano.

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