December 2020

Where do eye drops fit in the era of interventional glaucoma?

by Liz Hillman Editorial Co-Director

Open conjunctiva ab externo placement of a XEN Gel Stent. This technique can achieve a low target IOP, reducing or eliminating drops, while still providing a rapid visual recovery and favorable safety profile.
Source: Lori Provencher, MD

Where do drops fit in the era of interventional glaucoma—a time when there are new technologies, new drug delivery systems, and several MIGS options?
It’s a time where patients’ treatments can be fine-tuned based on their need and availability of these newer agents, said Leon Herndon Jr., MD, but he, Jella An, MD, Jacob Brubaker, MD, and Lori Provencher, MD, all said there is still a significant place in their practice for drops.
“From my standpoint, I think that medications serve a couple of roles,” Dr. Brubaker said. “One of them is if patients need adjuncts; in the more moderate to severe glaucoma, they, in a lot of cases, need more than one medication to be controlled. In those patients where they’re on 2–3 medications, it’s less likely that [selective laser trabeculoplasty (SLT)] or a sustained-release is going to be sufficient.”
Dr. An said more than half of her patient population at a university center in the Midwest has advanced glaucoma and a lot of other comorbidities.
“Drops still have quite an important place in my patient population,” she said.
Dr. Herndon said different treatment options are recommended for patients based on their current and target pressures.

Paradigm shift to first-line SLT

Where interventional glaucoma has its prime time, Dr. An said, is early in the disease process. All of the physicians said they offer SLT as a first-line therapy to newly diagnosed patients. Each mentioned the LiGHT trial as shifting the paradigm toward laser being considered a first-line therapy.1
Dr. An said she also offers SLT to patients with more severe glaucoma as well.
“I offer it to all patients regardless of severity, especially if they are experiencing side effects, issues with cost and compliance,” she said.
Dr. An cautioned overgeneralizing the LiGHT trial’s results because only 5% of the patients in the trial had more severe glaucoma. She reviewed data from her own patients, a sample size that included more cases of advanced glaucoma, looking for predictive factors that could impact outcomes of SLT and found patients with higher baseline IOPs had greater success rates and mean IOP reduction with SLT.2 She also said it’s important to monitor these patients closely because the effect of SLT can wear off, and the attrition rate is different for each patient. Dr. Provencher also said she mentions the importance of regular follow-up to SLT patients.
“A feeling of being medication-free has been one of the biggest concerns raised with first-line SLT and now more recently with intracameral delivery,” Dr. Provencher said. “Without the responsibility of a daily medication, will patients forget they have glaucoma and fail to follow up? Without proper counseling by their physician, it’s very possible.”
When counseling patients of their options, Dr. Provencher said she discusses the life-long compliance, side effects, and cost of drops in addition to the risks of SLT.
“I’ve found that most patients flinch at the word laser, but if you take the time to counsel on what to expect with SLT (painless, creates bubbles, takes under 5 minutes, etc.), they often reconsider. It is important to create an honest dialog about what treatment will work best according to each individual’s lifestyle and ability to adhere to the plan,” she said.
Different classes of drops
No drop is off the table for Dr. Provencher, who often treats complex glaucoma cases. In fact, most of the physicians who spoke with EyeWorld also said beta blockers, carbonic anhydrase inhibitors, and alpha agonist drops still have a place in their practice.
“I do discuss the decrease in compliance that occurs as we add on medications. With each mediation addition, I make sure to review alternative options, such as SLT or MIGS,” Dr. Provencher said.
Dr. Brubaker said the practice of adding single therapies as an adjunct is fading.
“For me, it’s typically moving on to a combination medication. … You’ll get more bang for your buck and you’ll get to a lower target in those cases. That’s where my practice has shifted, rather than adding one drop at a time,” he said.
Both Dr. An and Dr. Provencher said they opt for a once-daily prostaglandin analog, when they can.
“Rhopressa [netarsudil ophthalmic solution, 0.02%, Aerie Pharmaceuticals] is great for that reason as well, and now we have Rocklatan [netarsudil/latanoprost ophthalmic solution, 0.02%/0.005%, Aerie Pharmaceuticals], if a patient needs more than one class and the convenience of a single drop. I have been excited to see that insurance coverage of Rhopressa and Rocklatan is improving. I also consider Vyzulta [latanoprostene bunod ophthalmic solution, 0.024%, Bausch + Lomb] if patients do better with once-daily dosing but need a bit more IOP control than a PGA alone provides,” Dr. Provencher said.
Dr. Brubaker said Vyzulta shines in its side effect profile. Dr. An had a similar thought as well. She said compliance can be poor with Rhopressa and Rocklatan due to redness or changes in vision. She said Vyzulta is a good alternative for these patients, but it’s often not her primary choice because it’s not quite as effective, though still better than latanoprost alone.
All the physicians EyeWorld spoke with said it’s rare that they use miotic agents, outside of when the miotic effect is needed.
Sustained-release medications
Durysta (bimatoprost implant, 10 mcg, Allergan) was the first and is currently the only sustained-release, injectable glaucoma medication. Dr. Brubaker said he considers this, along with SLT, a first-line therapy, though he does think patients should trial on a prostaglandin drop to assess tolerance and what it’s like to administer regular eye drops.
There are several other sustained-release options still in the pipeline, including iDose (Glaukos), a bimatoprost-eluting ring (Allergan), the Evolute intracanalicular insert (Mati Therapeutics), the intracameral implant ENV515 (Envisia Therapeutics), and the intracameral implant OTX-TIC (Ocular Therapeutix). Durysta and the status of these pipeline product was in “Sustained-release making inroads in glaucoma” in the May 2020 issue of EyeWorld.

Standalone MIGS

The physicians EyeWorld spoke with said they currently perform MIGS as indicated in FDA labeling. iStent (Glaukos) and Hydrus Microstent (Ivantis) are approved in combination with cataract surgery, and none of the physicians interviewed use them regularly as a standalone. There are, however, a number of MIGS approved as standalone procedures that can serve a range of glaucoma severity.
“What we’re trying to do is find the right procedure for the right patient,” Dr. Herndon said. “There are some patient characteristics that I look for when I try to decide which of these angle procedures to recommend. It depends on the age of the patient, the type of glaucoma, the pressure goal that I have, the pigmentation of the angle. There are a lot of things that I’m putting into the equation when I tell the patient what I think will be the best option for them.”
Dr. Brubaker said there is a sweet spot for standalone ab interno canaloplasty, OMNI Surgical System (Sight Sciences), Kahook Dual Blade (New World Medical), and gonioscopy-assisted transluminal trabeculotomy (GATT). Patients who have mild glaucoma have the options of drops, SLT, and Durysta, while those with more severe disease and high pressures are better suited for tubes and XEN Gel Stent (Allergan), he said. For those in the middle with fair visual fields where medications and SLT have been tried but who you’re not quite comfortable moving toward a tube or XEN, these are the patients Dr. Brubaker thinks are suited for these standalone angle procedures. Given cost constraints and lack of coverage as standalone procedures, he said he has a hard time recommending treatment with Hydrus or iStent outside of cataract surgery.
Dr. An said if a patient is already pseudophakic, there needs to be a good reason to proceed with incisional surgery, especially in the COVID-19 era. Reasons include intolerance or incapacity to use medications. In these cases, she said she would choose XEN over an angle surgery.
Dr. Provencher expressed a similar sentiment regarding the need to consider the situation driving toward incisional surgery.
“It takes a strong patient-doctor relationship to abandon a ‘stable’ situation, where drops are controlling the glaucoma, and to proceed with incisional surgery,” she said. “You never want to talk a patient into surgery, and unless they come in miserable from ocular surface disease, side effects, cost, etc., it may take a few visits before a surgical discussion is appropriate or welcome.
“My approach is to empower patients to initiate the discussion and to feel comfortable discussing their options,” Dr. Provencher continued. “I want them to know I care about their quality of life and that I pay attention to compliance.”
Dr. An said with injectable and sustained-release medications and wider use of SLT as a first-line therapy, there is a good chance of replacing typical drop regimens in many patients if these interventional options are offered early.
“I truly hope that’s the case,” Dr. Herndon said of the envisioned future where drops are less relied upon to control IOP. “I would love to be 10 years from now and say the great majority of my patients’ glaucoma is well controlled without topical medication, be it they had a MIGS procedure or they had an injectable. There are other delivery systems coming out soon.”

About the physicians

Jella An, MD
Medical Director
Mason Eye Institute East
University of Missouri
Columbia, Missouri

Jacob Brubaker, MD
Sacramento Eye Consultants
Sacramento, California

Leon Herndon Jr., MD
Chief of Glaucoma
Duke Eye Center
Duke University
Durham, North Carolina

Lori Provencher, MD
Cincinnati Eye Institute
Cincinnati, Ohio

Relevant disclosures

An: Aerie Pharmaceuticals, Allergan, Iridex, Ivantis, New World Medical
Brubaker: Aerie Pharmaceuticals, Allergan, Glaukos, Ivantis, New World Medical
Herndon: Alcon, Allergan, Glaukos, Aerie, Sight Sciences, Ocular Therapeutix, New World Medical, Santen
Provencher: None


1. Gazzard G, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393:1505–1516.
2. Hirabayashi M, et al. Predictive factors for outcomes of selective laser trabeculoplasty. Sci Rep. 2020;10;9428.
3. Hirabayashi M, et al. Comparison of successful outcome predictors for MicroPulse laser trabeculoplasty and selective laser trabeculoplasty at 6 months. Clin Ophthalmol. 2019;13:1001–1009.



SLT studies

The LiGHT trial

An observer-masked, randomized, controlled trial of 718 treatment-naive patients with open-angle glaucoma or ocular hypertension and no other ocular comorbidities received either first-line SLT treatment (n=356) or eye drops (n=362).1 The primary outcome was health-related quality of life at 3 years, followed by secondary outcomes of cost, cost-effectiveness, disease specific health-related quality of life, clinical effectiveness, and safety. The researchers found more SLT eyes within their target IOP at more visits (93%) compared to those that received eye drops (91%). No patients in the SLT group in this timeframe required glaucoma surgery while 11 required surgery in the eye drop group. SLT was also determined to be more cost-effective than drops. The authors concluded that SLT “should be offered as a first-line treatment for open-angle glaucoma and ocular hypertension, supporting a change in clinical practice.” The authors wrote later that the results “support a change in clinical practice by providing evidence that primary SLT should be offered to treatment-naive patients with OAG and OHT.”

Predictive factors for SLT outcomes

In this study, Hirabayashi et al. evaluated the baseline characteristics and 2- and 6-month effect of SLT on 252 eyes from 198 patients with open-angle glaucoma.2 Success of SLT was defined as a 20% or more reduction in IOP or reduction of 1 or more medications without an IOP-lowering procedure. Age, type, and severity of glaucoma, trabecular meshwork pigment, total laser energy delivered, and baseline IOP were evaluated with success of the procedure. At 2 months, 33.6% of eyes were considered successful with SLT; 38.5% were successful at 6 months. A baseline IOP of more than 18 mm Hg was significantly associated with success of the procedure at both timepoints, with a mean IOP reduction of 5.4±5.3 mm Hg. Those with a lower baseline actually saw a mean increase in IOP (−0.7±4.6 mm Hg) at 6 months. Other characteristics such as age, glaucoma type, severity, TM pigmentation, etc., did not have an association with success of the procedure or IOP spikes.

MicroPulse laser trabeculoplasty vs. SLT

Hirabayashi et al. compared MicroPulse (Iridex) laser trabeculoplasty (MLT) with SLT in 100 eyes (50 eyes in each group) of patients who had open-angle glaucoma.3 Success of the procedure was defined as a 20% or more IOP reduction or reduction of one or more medications through 6 months of follow-up. Success of MLT and SLT was 44% and 40%, respectively. The researchers reported older age being a predictor of success for SLT but not MLT. Both procedures had greater IOP lowering in patients with a baseline IOP of more than 18 mm Hg. There was a significant association between SLT success with baseline IOP, and success with MLT was associated with number of laser shots. There was a higher rate of IOP spikes in the SLT group (none occurred in the MLT group). Overall, the investigators concluded that “older age and higher baseline IOP predicted success with SLT while MLT was equally efficacious regardless of these factors.” With no IOP spikes in the MLT group (10% in the SLT group), the authors also concluded that “MLT may be a safer alternative to SLT that is effective in lowering IOP and need for medications for a wider variety of patients with open-angle glaucoma.”

Where do eye drops fit in the era of interventional glaucoma?Where do eye drops fit in the era of interventional glaucoma?
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