Pharmacologic options for glaucoma have improved over the years. However, clinicians caring for glaucoma patients are challenged by the inability to control what product patients receive, because of insurance benefit dictates, or to trust that the patient is using medications as prescribed. Many an anecdotal story exists on how intraocular pressure (IOP) became uncontrolled after a patient switched from a medication that was working to one required by insurance. Also, despite any given patient really wanting to use the drops you prescribe, compliance is still lacking.¹ There are added issues with preservatives and the fact that many patients cannot hit their eye with the drop or put one drop in right after the other.^2,3

Many clinicians treating glaucoma have considered selective laser trabeculoplasty (SLT), which is relatively noninvasive. This trend was fueled by the LIGHT study, which showed success of SLT in controlling IOP when used as primary therapy.⁴ Less-invasive interventions like SLT are appealing as early interventions and often later in the treatment stream. However, some patients have trouble sitting at the laser, perhaps because they have a tremor or because they are too anxious. If a glaucoma patient has a cataract, minimally invasive glaucoma surgery (MIGS) can be performed with phacoemulsification, but standalone MIGS is not yet approved by the US Food and Drug Administration (FDA). Clinical trials have started to evaluate the less-invasive options as standalone therapy for patients with open-angle glaucoma.

Several sustained-release (SR) delivery therapies for glaucoma are in development, including latanoprost punctal plugs (Mati Therapeutics), a travoprost-containing intracameral delivery system (iDose; Glaukos), and a variety of intracanalicular and intracameral options (Ocular Therapeutix). On March 5, 2020, just at the start of the COVID-19 pandemic in the United States, the FDA approved a new intracameral, injectable option to deliver a very small amount of bimatoprost contained in an SR implant (Durysta; Allergan) directly into the anterior chamber (AC). Durysta 10 µg was approved for a single use. For the first time in glaucoma care, there is a long-term SR method to lower IOP. This article will discuss some additional specifics on where this new option might fit in the treatment paradigm, how those treating glaucoma might use it, and on whom and where it will be used.

Background and Clinical Trials

The SR material chosen to evaluate SR bimatoprost was that of an existing drug-delivery system that had proven effective in intraocular drug delivery, the Novadur dexamethasone drug delivery platform used for Ozurdex (Allergan). The biodegradable devices are constructed from synthetic aliphatic polyesters of the poly-α-hydroxy acid family, which include polyglycolic acid (PGA), polylactic acid (PLA), and the PGA/PLA copolymer, polylactic-coglycolic acid (PLGA).⁵ These compounds were adjusted in concentration to ensure safety for the ocular tissue and to control the release of the desired prostaglandin, bimatoprost. Bimatoprost seemed to be an excellent choice for many reasons to inject into the AC.⁶ Initially, the efficacy of various dose concentrations of bimatoprost was evaluated in vitro, and it was found that the drug was released in the beaker for weeks. Then the implant was tested in vivo in a canine model. The phase 1 studies in human subjects evaluated 4 concentrations of bimatoprost, and the overall balance of efficacy and safety appeared to be best in either the 10-µg or 15-µg implants.^7,8

The phase 3 trials for the bimatoprost SR implant were designed to evaluate both the 10 ug and 15 ug implant compared to timolol 0.5% BID plus a sham implant through week 12. After looking at the primary endpoint comparing the implants to timolol at week 12, the study was continued further. The idea was to load the tissue with more bimatoprost in an attempt to increase the duration of effect. There was no prior experience to draw upon, so the trial designers decided to inject an implant every 12 weeks up through 36 weeks, for 3 implants total. Then the investigators, of which I was one, would follow the patients. During the same time that the phase 3 trials were ongoing, extended monitoring of patients participating in the phase 1 trial showed that a single implant did yield a sustained duration of effect in lowering IOP for up to 2 years for about 25% of the subjects receiving the single implant.⁹ There may be an effect on the extracellular matrix of the uveal tissue allowing for an extended effect on IOP reduction.¹⁰ I presented the first results of the phase 3 data at the American Academy of Ophthalmology meeting in 2019.¹¹ The bimatoprost SR implant was shown to be noninferior to timolol. The publication of the phase 3 trial is in process at this time.

Durysta in Practice

Patients

Durysta is indicated for patients with ocular hypertension or open-angle glaucoma who require IOP reduction. There needs to be enough space in the angle to fit the implant so that there is no contact of the implant with the corneal endothelium. Gonioscopy should be done first to make sure there is enough space in the angle. An angle with a Spaeth gonioscopic grade D40 or Shaffer grade 3 or 4 should have ample room to fit the implant into the angle. Some narrower angles may have room but may risk contact of the implant with the cornea. The implant should stay in the AC so that if the patient has had cataract surgery, there is an intact capsule or the IOL is covering a capsulotomy. Implants should be avoided in patients with known conditions that put the corneal endothelium at risk, such as iridocorneal endothelial syndrome or prior transplant. Patients with or suspected to have pseudoexfoliative and pigmentary glaucoma are reasonable to consider for receiving the implant.

Procedure Scheduling and Location

The mechanics of injecting the patient will depend mostly on whether the injection is being performed at the slit lamp or in a minor procedure room. Initially, I plan to use the minor procedure room, because we used it during the clinical trials, and I had no issues with injection of the implant for either eye. Using my right hand, I could inject the right eye sitting at the head of the patient, and for the left eye, I would sit temporally. For the patients’ left eye, I would be comfortable using the slit lamp in the future.

For those using the minor procedure room, it may be best initially to schedule time for the patients to receive the injection. Designating a “Durysta Day” or something similar can ease the process for several reasons. Because Durysta is new, creating a protocol for injection and practicing it with repetition can improve efficiency. The staff (coding/billing, techs, and schedulers) can become comfortable with setting up and preparing the necessary items for the procedures that day. Magnification (microscope or slit lamp), something to prep the eye, and a lid speculum will be needed.

A separate day also allows for obtaining authorization for the injection. There are components to the billing that may be challenging in the early days after FDA approval. The procedural code will most likely be 66030 (Injection, anterior chamber of eye [separate procedure]; medication). For the medication, initially you would use the miscellaneous J-code J3490 until a permanent J code is established. For some insurance carriers, the miscellaneous code for the implant is not an issue, whereas others may require more documentation.

Some practices may elect to buy the implants outright and bill the patient for them. Other practices will use a specialty service option from a pharmacy. This option is available for most pharmacy benefit plans and is used for therapies like rheumatoid arthritis medications and intra-articular hyaluronic acid. The pharmacy will work through the insurance and cost issues with the patient and send the medication to your office or the patient. This does relieve some of the prior authorization issues for the medication itself, and also the financial burden is shifted off the practice’s plate. The patient would need to get all this done in advance of receiving the Durysta implant.

Physicians might also choose the ambulatory surgery center for performing the injection. This would involve evaluating all related costs and coding. I plan to start by scheduling a patient several weeks out, getting prior authorization for the CPT code (if needed), and having the patient go through the specialty service pharmacy and get the medication to me in time for the procedure. It is unclear how much the office will need to facilitate the specialty pharmacy process beyond placing the order.

Implanting the Device

On the day of the procedure, review the potential recipients’ records. Make sure you are comfortable with factors that may change the risk from when you first scheduled the procedure. For instance, if a patient is on a new anticoagulant, it is reasonable to discuss that the risk of bleeding in these circumstances is not known. Double check that the angle is open sufficiently and that the cornea does not have predisposing issues to the endothelium, such as iridocorneal endothelial syndrome. Obtain the consent. Review the risks and benefits of the Durysta. Identify the patient and mark the eye to receive the Durysta.

Set up the sterile field for the procedure. Because we are still in the COVID era, I plan to wear a mask and ask everyone in the room not to speak while injecting. The patient will be supine in the minor procedure room, mostly likely with a cap. I will sit above the head for the right eye and temporal for the left and use my right hand. After a hand scrub, with the mask on, I will prep the eye. I plan to use the 5% povidone-iodine, because it does not burn as much and has been shown to be as effective in preventing infection as 10% povidone-iodine.¹² A drop will be placed initially after topical anesthesia.

After the speculum is placed, a second drop of 5% povidone-iodide will be placed. Sterile gloves are applied, and we will then apply more topical anesthesia and position the microscope over the patient’s eye. The assistant will peel open the Durysta container and I will remove the injector. The tip of the needle is exposed and inspected under the microscope. A clear corneal paracentesis entry is made into the AC with the 28-gauge needle (Figure 1; see an animation of the implantation technique below). The implant is injected, and care is taken to make sure the implant is not on the tip of the needle. If it is, a gentle tap usually dislodges the implant. The needle is slowly withdrawn, and the wound is checked to make sure the implant did not follow the needle to the wound. If it did, open one of the wire spatulas designed to push this out of the wound and into the AC. Check the wound and remove the speculum.

There is little evidence that the use of topical antibiotics makes a difference in preventing endophthalmitis after intravitreal injections, so I am not likely to use them for intracameral injections.¹³ The patient will then be scheduled for a 1-week follow-up appointment. If all looks good, I will likely follow the patient every 3 months. As long as patients’ IOP is acceptable, I will watch. If pressure starts to drift up, I most likely will use bimatoprost, because patients have a loading dose with the implant; however, there are no data to support this.

Conclusion

Sustained-release treatment is a brave new world in glaucoma therapy. With the approval of an SR implant, glaucoma specialists have a new tool at their disposal that could help patients achieve intraocular pressure control without drops, or with fewer drops, easing the burden of therapy and compliance. GP

E. Randy Craven, MD, FACS, is chief of the Bethesda location of the Wilmer Eye Institute, vice chair for Wilmer network of locations, and an associate professor at Johns Hopkins University in Baltimore, Maryland. He reports consultancy to Allergan. Reach him at ecraven1@jhmi.edu.

References

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