Glaucoma care is rapidly evolving to embrace non-drop interventions like selective laser trabeculoplasty (SLT), microinvasive glaucoma surgery (MIGS) and even sustained-release drug delivery earlier in patients’ treatment regimens. Although topical drop therapy is commonplace, the associated adherence and persistence challenges are such that alternative approaches are required, says Nathan M. Radcliffe, MD.
“When we try to take the pharmacologic model that we enjoy in society mostly with oral pharmacotherapy and move it over to topical eyedrop therapy, things really fall down,” says Dr. Radcliffe, associate clinical professor of ophthalmology at Mount Sinai School of Medicine in New York. “Long-term administration of eyedrops presents a tolerability dilemma.”
While we have seen formulary advancements with potent once-a-day therapies, preservative-free options, and formulations with newer types of preservatives, ideally, “We want to use fewer drops,” he says.
IMPACT ON EYES AND BODY
We cannot overemphasize the impact that topical drops have not only on the corneal surface, but also on the conjunctiva and the eyelids, says Inder Paul Singh, MD.1-7 “They all have the potential to cause significant symptoms to patients which, at the end of the day, is what they care about the most. We don’t want the treatments to cause more symptoms or quality-of-life issues than the actual disease.” Dr. Singh is the president of The Eye Centers of Racine & Kenosha in Wisconsin.
“Prostaglandins (regardless of if formulated with a preservative or not) have been shown to cause goblet cell loss setting off a loss of tear film homeostasis and a host of dry eye symptoms,” Dr. Singh says. “Added preservatives can lead to more fibrosis of the conjunctiva, which is problematic for any future conjunctival surgery, and chronic dry eye can cause inflammation of the trabecular meshwork and the collector channels, which can increase pressure over time.”
While these drops may seem relatively benign, there are also systemic side effects to topical drug therapy that can have major effects on people’s health, mood and quality of life.8
“Beta-blockers can cause depression and alopecia, for example, and alpha-agonists can cause light-headedness, orthostatic hypertension and dry mouth. These are surprisingly common systemic issues,” says Manjool M. Shah, MD, who is in practice at NYU Langone and is associate professor, Department of Ophthalmology, at NYU Grossman School of Medicine in N.Y. “You combine all of these factors, and of course folks don’t want to take drugs that irritate their eyes and cause all these issues for a disease they don’t feel or recognize until they have already lost vision.”
The real point of resistance when it comes to getting patients off topical medications is their misconceptions about eyedrops being the best approach for glaucoma therapy, notes Dr. Radcliffe. “It falls upon us as the clinicians to educate our patients on the side effects of topical drops, on the reality of how difficult compliance can be, and even on the fact that eyedrops aren’t always the ideal way to treat a disease that’s chronic, lifelong and progressive.”
Unfortunately, we’re not at a place yet where drops don’t exist in the treatment tool kit, says Dr. Shah. “I tell my patients that what I’m working toward and where the field is going is that drops serve as a bridge to a more definitive therapy. While drops work, they’re an imperfect solution, so we should be looking to treat disease in a targeted approach.”
The surgeons agreed that drops are still needed, but the key is to minimize the amount and the impact. “We don’t have to rush to do three and four and five medications. We can do an SLT or use a drug-delivery option and think about MIGS before we add a second drop,” says Dr. Singh. “I think we need to push toward using drops as needed, not necessarily as a concrete algorithm where you have drops, drops, drops, then laser, then drops, then MIGS.”
EVOLVING OPTIONS FOR FIRST-LINE THERAPY
Selective laser trabeculoplasty
SLT has finally arrived as the primary and proven ideal first-line therapy for glaucoma, Dr. Radcliffe says.9 “The results of the 6-year extension of the LiGHT Study showed that, despite lowering pressure about the same as latanoprost, patients who had laser had better long-term disease control than those receiving initial drop therapy, with reduced need for incisional glaucoma surgery and less visual field progression.”
Dr. Singh adds, “I say to patients my goal is to do what I can to protect you from losing vision from glaucoma and give you the highest quality of life. We don’t have to be afraid to say, [SLT] is our first-line treatment now. In my clinic, SLT is standard of care, and we should feel good about telling that to patients.”
Sustained-release drug delivery
Sustained-release drug delivery became a reality when the FDA granted approval to Allergan’s bimatoprost biodegradable intracameral implant (Durysta), designed to deliver drug to the target tissues for several months.10 “We have learned that up to 80% of patients receiving Durysta will enjoy IOP control for a year,” Dr. Radcliffe says. “Even though the drug only lasts in the eye for 4 months, many patients benefit for a much greater period of time, possibly because of remodeling in the uveoscleral outflow. This gives it a nice place in a drop-free paradigm, which can either be done with SLT, in place of SLT or after SLT begins to wear off.”
The iDose TR, Glaukos’ single administration per eye travoprost intracameral implant, received FDA approval last year.
MIGS
Beyond the MIGS options approved for use with cataract surgery, a number of options exist in the standalone MIGS category. “Surgeons may have a varying level of comfort with different techniques: goniotomy and canaloplasty can be performed as standalone procedures, and there are a variety of instruments available to achieve these interventions,” Dr. Radcliffe says.
Standalone MIGS via goniotomy can be performed with Trabectome (MicroSurgical Technology); gonioscopy-assisted transluminal trabeculotomy, or GATT; Kahook (New World Medical); and SION (Sight Sciences). Canaloplasty can be done with iTrack Advance (Nova Eye Medical) and OMNI (Sight Sciences). The Streamline Surgical System (New World Medical) is a device designed to create goniotomies and canaloplasty in one step.
“We now have the ability to deploy trabecular bypass stents with the iStent infinite (Glaukos) achieving FDA approval as a standalone trabecular bypass procedure,” Dr. Radcliffe adds.11 “This was studied in refractory glaucoma patients, but patients who are not tolerating their topical therapy and have undergone a laser procedure can certainly be considered to have refractory glaucoma and are excellent candidates. The iStent infinite offers an excellent procedure with rapid recovery time that allows patients to maintain an excellent quality of life with lower IOPs and a reduced or eliminated need for topical therapy.”
The standalone iStent infinite consists of three stents to create a direct pathway through the trabecular meshwork for aqueous humor outflow. Also, the XEN Gel Stent (Allergan) provides an alternative pathway for drainage and requires mitomycin for successful bleb creation.
TREATMENT APPROACHES
With all of these available options for treating glaucoma, how can they potentially work together?
Dr. Shah lays out all options for his patients so there are no surprises. He tells them, “We start with SLT, if we don’t get what we want, we do another round of SLT,” because that strategy was effective in the LiGHT trial protocol. “After that, if we still need more therapy, we start thinking creatively with sustained drug-delivery and standalone MIGS. Certainly, if this is a patient who is approaching cataract age, we may be able to preemptively do cataract surgery plus MIGS.”
Data from the LiGHT Study also indicate that a sustained method of pressure lowering, such as laser, a drug-delivery implant or MIGS, does a better job of controlling the disease than topical drop therapy, says Dr. Radcliffe. “Likely due to the fact that it limits IOP fluctuation because the therapy is administered once, whereas eyedrops need to be administered once or twice a day and even have significant variability in their efficacy throughout that 24-hour period.”
Also, patients treated with SLT and MIGS have better corneal health with an improved ocular surface when compared to drop therapy and less endothelial damage when compared with traditional glaucoma surgeries such as trabs and tubes, say the surgeons interviewed.
CONCLUSION
There is no question that, in 2024, we still need drops, says Dr. Shah. “No therapeutic modality works faster than a drop, but we do pay for that. There will be situations where we need rapid reduction or we need a bridge between intervention A and intervention B, so we cannot cross anything off the list prematurely. If, however, the core principle is achieving the best quality of pressure control and, as much as possible, treating the target tissues, then maybe we need to think about putting drops in a separate category.”
To Dr. Singh, the interventional glaucoma mindset is about maintaining a high quality of life and addressing IOP at the same time without having to choose between either one of them. “We have a number of tools, procedure-wise, that can limit the use of drops — if we utilize them appropriately. My definition of success with these is not just absolute reduction of IOP; it’s trying to reduce the medication burden, which has a huge benefit for the patient and also increases their trust in our therapies.”
The technology exists for glaucoma specialists to provide drop-free options to glaucoma patients.12 “The beauty of having all of these options is that we can confidently discuss them with our patients and tailor the appropriate therapeutic options to their specific needs and clinical situation,” Dr. Radcliffe says. OM
Dr. Radcliffe disclosed relationships with Allergan, Glaukos, Iridex, Lumenis, New World Medical and Sight Sciences. Dr. Shah disclosed relationships with Alcon, Allergan, Glaukos and Nova Eye Medical. Dr. Singh disclosed relationships with AbbVie/Allergan, Alcon, Glaukos, New World Medical, Nova Eye Medical and Sight Sciences.
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