What’s New In Glaucoma?

Episode 1
Several new topical therapies are now available for the treatment of elevated intraocular pressure (IOP) and glaucoma. Netarsudil is a rho kinase (ROCK) inhibitor that was shown to result in about a 20% reduction in IOP when combined with either a prostaglandin or multiple drug classes (Figure 1).¹ Similar results were also observed in the ROCKET trials when netarsudil was used as monotherapy.² Next, preservative-free latanoprost effectively lowered IOP, although it did not meet the noninferiority margin of 1.0 mmHg for the majority of analyzed timepoints in the phase 3 US clinical trial.^3,4 Finally, omidenepag isopropyl (OMDI) is a selective, nonprostaglandin prostanoid EP2 receptor agonist that was shown to be noninferior to latanoprost with fewer periorbital changes.⁵ These agents provide a greater number of options to personalize glaucoma therapy for each patient.



Figure 1. MOST study outcomes with netarsudil added to prostaglandin analog and multiple drug classes.

Episode 2
Two approved sustained-release (SR) treatments are now available. The bimatoprost intracameral implant is a biodegradable polymer that releases bimatoprost over 3 to 4 months. ARTEMIS-1 and -2 were randomized multicenter trials that showed the bimatoprost implant was noninferior to timolol BID at Week 12.^6,7 The average IOP reduction was 7.7 mmHg with the bimatoprost implant and 7.1 mmHg in the timolol group. The bimatoprost implant has been limited to a single application due to the risk of endothelial cell loss. 

The iDose TR implant is a travoprost preloaded SR device requiring surgical insertion to anchor it to the sclera via the trabecular meshwork. Phase 3 data showed 81% of patients were free of topical medications after one year.⁸ Overall, the implant bested topical prostaglandins by about 1.3 mmHg. More SR treatments are in development, offering the advantage of better adherence with fewer ocular surface disease side effects.

Episode 3
Reducing treatment burden can help improve a patient’s quality of life. A patient with normotensive glaucoma had a worsening right eye as demonstrated with optical coherence tomography (OCT) and visual field progression. His IOP was 15 mmHg OD and 14 mmHg OS with a T_max of 17 mmHg OU. A disc hemorrhage was observed at the 10 o’clock position and the cup-to-disc ratio was 0.8. OCT showed thinning in both the temporal superior and inferior quadrant over a 3-year period and a ganglion cell defect. Visual field testing showed a paracentral defect. His current treatment of latanoprostene bunod QD OU was switched to combination latanoprost/netarsudil QD. Six weeks later his pressure was reduced to 11 mmHg OD and 10 mmHg OS.

Other patients are good candidates for SR therapy. A 91-year-old pseudophakic woman with visual acuity of 20/40 OD, 20/30 OS, and target IOP of 14 mmHg OU was having a difficult time with drop instillation with the prescribed fixed-dose combination dorzolamide/timolol/latanoprost. Instillation was a burden on both her and her daughter, who was a primary caregiver. The patient’s ocular surface was also bone dry. After bilateral sequential intracameral bimatoprost implants, her pressure was stable at 14 mmHg and she reported that the treatment was “life-changing” for her. 

Episode 4
Minimally invasive bleb surgeries (MIBS) allow surgeons to perform less invasive procedures compared to trabeculectomy. The XEN Gel Stent (XEN) creates a low-lying bleb in the subconjunctival space and is a good approach for patients who have had prior minimally invasive glaucoma surgeries (MIGS) and need better pressure reduction. PRESERFLO is another technology available in Canada and some other countries. It is still under investigation in the United States.

The Gold-Standard Pathway Study (GPS) compared XEN and traditional trabeculectomy.⁹ Results showed that XEN was noninferior to trabeculectomy with respect to achieving >20% IOP reduction without hypotony, vision loss to counting fingers, and medication increase. The XEN group tended to have better visual acuity recovery and fewer patients with decreased vision affecting their daily functionality compared to trabeculectomy (Figure 2). There was also less chance of hypotony associated with XEN. This has allowed for bleb-type surgery in patients with moderate disease.



Figure 2. Gold-Standard Pathway Study (GPS) secondary outcomes. 

Episode 5
iStent inject (iStent) and Hydrus Microstent (Hydrus) are both recommended by the American Academy of Ophthalmology as MIGS for Schlemm’s canal. iStents are 80-µm stents spaced 2 to 3 clock-hours apart to bypass the trabecular meshwork. Hydrus acts as a scaffold to the Schlemm’s canal, spanning 3 clock-hours and allowing access into the collector system. 

Results from the COMPARE study evaluating two iStents versus Hydrus as standalone procedures found no significant differences in IOP reduction after 12 months.¹⁰ Safety profiles were similar. Study limitations included fewer iStent eyes undergoing treatment washout and sample sizes too small to fully evaluate safety differences.¹⁰ The HORIZON study examining Hydrus + cataract surgery versus cataract surgery alone showed lower IOPs and more medication-free eyes after 5 years with Hydrus (Figure 3).¹¹ Also, the need for major glaucoma surgical intervention in the Hydrus group was reduced. Overall, iStent and Hydrus have similar safety profiles and effectively reduce IOP.



Figure 3. Select 5-year outcomes from the HORIZON study.

Episode 6
The suprachoroidal space is a new target for MIGS procedures. The CyPass was the first suprachoroidal drainage device on the market but was voluntarily removed due to endothelial cell loss. iStent Supra and MINIject are two new devices in development that utilize this space.

The benefit of targeting the suprachoroidal space is not having to worry about other potential barriers to resistance, and there is a significant degree of IOP reduction because it has a negative pressure gradient. Risks associated with suprachoroidal MIGS include closing of the space, which can lead to significant pressure spikes, hyphema, and vitreous hemorrhage. The suprachoroidal space is becoming increasingly important with more companies producing new technologies for accessing and managing the space. 

Episode 7
There is not a one-size-fits-all strategy to selecting a MIGS device for each patient. Decisions depend on the anatomy, cataract status, and medication burden of the patient, as well as the technology being used and the comfort level of the surgeon. For Dr. Singh, 5-year HORIZON trial data support the use of a Hydrus Microstent (Hydrus) in a patient who has mild to moderate glaucoma and is using 1 to 3 medications.¹¹ The Hydrus scaffolds rather than bypasses the trabecular meshwork, improving access to the collector channels. 

A XEN Gel Stent (XEN) is also an option for many patients. Dr. Petrakos elected to insert a XEN in an 83-year-old woman with moderate primary open-angle glaucoma who uses 3 preservative-free drops. Three years after the surgery, the patient’s IOP is around 10 or 11 mmHg and she is drop-free. Managing Tenon’s capsule by performing primary needling to reduce the risk of fibrosis is key to successful XEN procedures. 

Episode 8
Back pain is one of the most common reasons that surgeons consider early retirement. A 2005 survey showed that 15% of ophthalmologists (N = 697) curtailed their work because of back and neck pain.¹² Another survey of 130 ophthalmologists found that 73% experienced pain while performing surgery.13 Indeed, for every inch that the neck is forward, 10 lbs of weight is place on the cervical spine. 

3D heads-up displays allow ophthalmologists to be free from using the oculars and sit up straight during surgeries. Ngenuity, Artevo, and Beyeonics are all heads-up systems. Ngenuity and Artevo use external displays to provide a 3D view while Beyeonics uses a headset to provide a 3D view no matter where you turn your head. Pay attention to ergonomics to minimize neck and back pain. New 3D heads-up display systems can improve the longevity of your practice while providing a great surgical view for improved communication with students and coworkers. 

Episode 9
There is a learning curve to using 3D heads-up systems in the operating room. The first step is to get out of your comfort zone by trying these systems. Start by only performing a portion of the case, such as initial incisions, and avoid switching between the oculars and 3D display during a surgery. Give yourself 2 or 3 full days to become comfortable with its use. 

Determining preferred settings can be challenging, and company representatives can help with understanding the nuances of the technology. The best place to position the screen is perpendicular to the surgeon. Since a surgeon’s body and eyes can be decoupled from the oculars, the patient’s positioning can be changed to help the surgeon stay comfortable. Also, begin with surgeries that are straightforward and plan for extra time when learning to use 3D systems.

Episode 10
Using 3D heads-up systems can help reduce neck and back pain after performing surgery. Additionally, 3D heads-up systems can help keep everyone in the operating room on the same page, including residents, fellows, retina or cornea colleagues, and technicians. Medical students who are curious about ophthalmology can also feel more involved. Additionally, staff can be more proactive and hand things to the surgeon before being asked since they are able to watch the surgery in real time. 

The 3D systems can also provide improved visualization of the angle when performing MIGS. The depth of the view through the gonioprism is great and can help surgeons more easily determine how they want to approach the angle. Some systems also have the ability to change the color saturation, bring up green or red colors, and change the contrast to better highlight the trabecular meshwork compared to traditional scopes.


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