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Direct selective laser trabeculoplasty is an automated, transscleral, 1-second procedure that holds promise for increasing accessibility to IOP-lowering treatment. Clinical trials are under way.
An investigational IOP-lowering modality, direct selective laser trabeculoplasty (DSLT) (BELKIN Laser), is being developed for its potential as a first-line treatment for ocular hypertension (OHT) open-angle glaucoma (OAG) and possibly for angle-closure glaucoma (ACG) that overcomes the limitations of current initial therapeutic options.
The non-invasive, non-contact procedure is performed with automated laser technology that delivers 100 spots to the trabecular meshwork through the limbus in just 1.2 seconds.
A proof-of-concept study provided evidence for the efficacy and safety of the transscleral approach to laser beam delivery using a conventional SLT instrument, and studies are under way outside of the United States using the external automatic glaucoma laser device itself.
The aim is to provide a solution for addressing the growing worldwide burden of glaucoma-related vision loss, said Michael Belkin, MD, MA, inventor of DSLT and founder/medical director of BELKIN Laser, Yavne, Israel.
“Poor patient compliance and accessibility to medications limits success with medical management of glaucoma,” said Dr. Belkin, who is also professor of ophthalmology and director, Ophthalmic Technologies Laboratory, Goldschleger Eye Research Institute, Tel Aviv University Sheba Medical Center, Tel Hashomer, Israel.
Many studies have established that SLT is an appropriate first-line option for IOP-lowering, and most recently, results from the Laser in Glaucoma and ocular HyperTension (LiGHT) trial showed that SLT was more cost-effective than medication when used in treatment-naÃ¯ve patients [Lancet. 2019;393:1505-1516], according to Dr. Belkin.
“SLT, however, is generally performed only by glaucoma specialists because it requires expertise with gonioscopy,” he added.
“The reality, however, is that even in areas in developed countries, there are not enough glaucoma specialists to meet the need for services, and the disparity between demand and supply is far worse in developing nations around the world,” he said.
DSLT can make laser treatment for IOP-lowering broadly accessible to patients around the world because it is performed without need for a goniolens or slit-lamp delivery system, according to Dr. Belkin.
“Over the past years, innovations to treat glaucoma typically focused on invasive therapies, rather than first-line solutions,” said Daria Lemann-Blumenthal, LLB, EMBA, chief executive officer of BELKIN Laser.
“Our purpose . . . is to increase accessibility to glaucoma care by offering a very simple, automated, 1-second laser treatment that can be performed as an initial treatment by all ophthalmologists at any location,” she added. “Our professional team and key opinion leaders are committed to bring this sophisticated technology to the market and support its safety and efficacy through well-designed clinical studies.”
Sir Peng Khaw, MD, PhD, professor of glaucoma and ocular healing, University College London and Moorfields Eye Hospital, London, described DSLT as exciting technology because of its convenience and ease of use.
Considering the results of the LiGHT trial and the promise that DSLT has shown in early investigation, DSLT seems poised to create a significant paradigm shift in the treatment of OHT and OAG, he noted.
“The LiGHT trial showed that SLT worked better than medications as initial IOP-lowering treatment,” Dr. Khaw said. “Compared with conventional SLT, DSLT offers a potential method for delivering laser treatment more simply and to more patients.
“If ongoing studies prove that the efficacy of DSLT is equivalent to SLT, DSLT will have a real role in allowing us to meet the growing demand for glaucoma treatment in populations around the world,” Dr. Khaw added.
Its potential impact is significant considering that glaucoma is the second-leading cause of irreversible blindness globally and that the number of people affected by this disease is expected to increase exponentially in the coming years, he noted.
Richard L. Lindstrom, MD, added that DSLT holds promise as an approach that can provide the benefits of SLT in a procedure that is much easier for both the physician and the patient.
“Based on its efficacy and safety, SLT is widely accepted as an appropriate alternative to medications as a first-line IOP-lowering treatment,” said Dr. Lindstrom, adjunct professor emeritus, Department of Ophthalmology, University of Minnesota, Minneapolis.
“DSLT brings the opportunity to expand the use of SLT by making it feasible for patients who otherwise might be considered poor candidates because they are uncooperative and in areas lacking the ancillary instrumentation and sophisticated personnel needed to perform traditional SLT,” he said.
Trials that definitively establish the efficacy and safety of DSLT need to be completed, but the preliminary evidence about its outcomes is encouraging, he noted.
CONCEPT AND DESIGN
Dr. Belkin-who also invented a minimally invasive glaucoma surgery device (EX-PRESS, Alcon Laboratories)-said he developed the idea for DSLT based on the realization that sufficient energy could reach the trabecular meshwork if the 532-nm wavelength used for conventional SLT was applied directly to the overlying sclera.
His original vision was to create a system that could automatically deliver all 100 laser spots simultaneously. Ultimately, he had a a system designed that delivers the 100 spots at the limbus in rapid sequence.
Spot delivery is achieved using a scanner and the investigational DSLT device also incorporates an advanced image-processing algorithm that accounts for eye movement and locates the exact treatment area.
GATHERING THE EVIDENCE
Dr. Belkin collaborated with Noa Geffen, MD, and colleagues at Meir Medical Center, Kfar-Saba, Israel, to undertake a proof-of-concept study to demonstrate that if application of the laser spots through the sclera lowered IOP as effectively as standard SLT [J Glaucoma. 2017;26:201-207].
The randomized study included two groups of 14 patients each. The control group was treated with traditional SLT and the study group was treated with the same SLT device but with transscleral delivery of 100 laser spots to the trabecular meshwork without the use of a goniolens.
Analyses of data collected after 6 months showed no statistically significant differences between the two treatment arms in mean IOP reduction or success rates whether success was defined by achieving a ≥15% reduction from baseline IOP or a ≥20% decrease.
The overall rate of procedure-related adverse events was significantly lower in the group treated with transscleral SLT.
Data on individual adverse events showed that both anterior chamber inflammation and superficial punctate keratitis were significantly less common in the study group compared with the controls, and the difference between treatment groups in the rate of ocular discomfort that also favored the transscleral group nearly achieved statistical significance.
“The goniolens and its rotation on the cornea can produce corneal lesions and patient discomfort, and it also obviates the need for the goniolens contact gel,” Dr. Belkin said. “These issues are avoided with non-contact DSLT.”
Initial preclinical studies conducted with a prototype of the DSLT device provided evidence of its safety. DSLT is currently being investigated in a multinational, prospective, randomized, controlled study comparing it with standard SLT.
Funded by a €2.5 million grant from EU Horizon 2020, the study is under way at Universita degli Studi di Genova, Genova, Italy. Patient recruitment will be starting soon at Queens University Belfast, Moorfield Hospital, London, and Beilinson Medical Center, Tel Aviv, Israel.
Eligible patients are age 40 years or older and have visual acuity >6/60 in both eyes, OAG including exfoliative or pigmentary glaucoma, IOP ≥ 22 mm Hg to ≤35 mm Hg (after washout of any IOP-lowering medications), a gonioscopically visible scleral spur for 360° without indentation, and a visible peri-limbal sclera for 360° with use of a lid speculum.
The study has a non-inferiority design and is comparing the difference between the SLT and DSLT treatment groups between the mean baseline IOP and the mean IOP at 6 months after treatment as its primary outcome measure.
A single-center, dose-response study under way at Goldschleger Eye Institute, Sheba Medical Center, Ramat-Gan, Israel, is a 6-month trial enrolling patients with uncontrolled OAG who will undergo DSLT in one eye.
The study is including patients age 18 years or older who have an average IOP of at least 22 mm Hg measured at two pre-treatment visits in the eye that will be treated. It is enrolling 15 patients.
Initial patients were treated with an energy of 0.8 mJ dose, the same as that used for conventional SLT, and the energy is being escalated.
“Some of the laser beam is absorbed in the sclera and some of it is also scattered,” Dr. Belkin explained. “While scatter is desirable because it means more trabecular meshwork cells will be impacted, there is still a threshold level that needs to be achieved for the desired activity.”
So far, data are available from 3 patients who completed 6 months of follow-up.
Results in this small group show that IOP was reduced by an average of about 25%, which is comparable to the benefit associated with conventional SLT, Dr. Belkin said.
Safety has been favorable. In the second patient enrolled in the study, the treatment missed its mark, being delivered to the conjunctiva away from the limbus, and the patient developed a small hemorrhage that resolved within a few days.
“A modification of the system has solved the potential for that occurrence,” Dr. Belkin said.
“The only other side effect has been transient blurred vision that occurred after the procedure in the first three patients,” he said. “We think the blurriness may be related to the brightness of our illumination LEDs and has not occurred since an adjustment was made.”
Dr. Belkin noted that DSLT is performed under topical anesthesia, and added that none of the 12 patients treated so far in the dose-response study felt any pain.
EXPANDING THE INDICATION
Planning is also under way to conduct studies of DSLT in China, including as a treatment for angleclosure glaucoma.
Because the treatment is delivered through the sclera and does not require visualization of the angle, DSLT may be a viable treatment for primary angle-closure or primary angle-closure glaucoma, according to Dr. Belkin.
“Results of a study done in Singapore showed that eyes with primary angle-closure or primary angle-closure glaucoma respond well to SLT [JAMA Ophthalmol. 2015;133:206-212.]
Because of the need to visualize the angle with a gonioscopy lens, however, patients were only eligible for SLT if the angle was opened at least 180°.
“There would be no such restriction for patient selection when performing DSLT,” Dr. Belkin explained.
“Angle-closure glaucoma accounts for about 30% of glaucoma cases worldwide and for the majority of irreversible blindness in Asia, and there is a major unmet need for better treatments for this common disease,” he said.
PENG KHAW, MD, PHD
Dr. Khaw is on the medical advisory board of BELKIN Laser.
RICHARD L. LINDSTROM, MD
Dr. Lindstrom is chair of the medical advisory board of BELKIN Laser.