While topical glaucoma medications are generally safe and effective, these agents have numerous caveats that limit their long-term efficacy and sustainability.¹ Shortcomings include nonadherence (with risks of glaucoma progression and vision loss), suboptimal IOP control with circadian fluctuations, complex dosing regimens, physical challenges performing dosing, side effects (such as ocular surface disease [OSD]), the burden of treatment costs and, ultimately, a negative effect on overall quality of life.¹

Despite these caveats, topical glaucoma medications have remained first-line therapies in the glaucoma toolbox, with prostaglandin analogs being the most frequently prescribed.2 Problems with glaucoma medication adherence can lead to poorly controlled IOP and worsened clinical outcomes.³ Studies report wide ranges (up to ≥80%) for estimates of adherence for these medications.³ Numerous barriers contribute to suboptimal adherence, including patient health literacy, difficulty with drop administration, treatment regimen complexity, cost and side effects.⁴

Recent innovations in drug delivery, however, may significantly reduce — even eliminate — these shortcomings. Here’s a look at the latest in industry’s solution, novel procedural pharmaceutical devices.

THE PARADIGM SHIFTS

The glaucoma treatment paradigm is shifting toward a procedural-based interventional approach1 that makes use of agents with different mechanisms of action, alternative drug delivery devices, safer subconjunctival surgery, minimally invasive glaucoma surgery (MIGS) and laser trabeculoplasty.^1,2 Because of these innovations, it is becoming increasingly feasible to intervene earlier in the disease process and to shift the treatment strategy from a reactive to a more proactive paradigm termed “interventional glaucoma.”¹ 

This new paradigm includes early procedural intervention that addresses patient adherence and risk of progression. Laser surgery, MIGS and minimally invasive bleb surgery come under the heading of early procedure intervention — as well as novel procedural pharmaceutical devices.

DURYSTA

Procedural pharmaceutical devices have the potential to change the glaucoma treatment paradigm by directly addressing the challenges of topical medication adherence.5 In 2020, one device was FDA approved for this application — a biodegradable bimatoprost sustained-release (SR) intracameral implant (Durysta, Allergan).⁵ Since Durysta’s release and subsequent use in patients, clinical and procedural pearls have emerged.

DURYSTA IN THE CLINIC

Here I will share the clinical lessons I’ve learned since I began incorporating Durysta in my practice. 
I’ll start with two major questions about patient selection.
1. Phakic or pseudophakic patients? Both are appropriate and approved for use. However, for doctors new to Durysta, starting with pseudophakic patients may be easier.
A. The patient will have a deeper anterior chamber as the natural lens has been removed. Directing the bevel into the eye and avoiding the iris and cornea is easier. Also, this helps to further minimize risks of long-term implant to endothelium contact.
B. The patient has already gone through a prior eye procedure that was more involved (cataract surgery). In this case, you should discuss with the patient what they can expect as a baseline.

2. Can it be used only on patients on one drop, or can it be used on those on multidrop regimens? Given the high degree of medication non-compliance, selecting patients on one or two drops can be a good starting point. You can consider asking the patient to stop their drop(s) and reassess their IOP 2-3 weeks later. This trial can help assess which patients were actually more non-compliant.

Now for some procedure pearls for successful Durysta insertion:
1. Appropriate setting for insertion. Should it be done in the office using a slit lamp with the patient sitting or in a surgery center with the patient laying supine? This depends on what’s best for the doctor and patient. Depending on OR availability, some doctors feel patients have a more comfortable experience at the surgery center. They get to lay down with their head relaxed and not subconsciously moving their head back as something approaches it. It is also perceived to be a very sterile environment of an OR. However, if there is lack of OR access, some feel using a slit lamp in the clinic works just as well and may be more convenient for patients.
2. Best depth and length of injection. The main goal is to be in the anterior chamber and past the cornea prior to deployment. A good target is to have the bevel halfway between the inferior angle and inferior pupillary margin.
3. Proper activation on the plunger. It is important to remember that the success of Durysta deployment can be influenced by how the doctor presses on the activator. Make sure to give a rather strong and confident push on the button to obtain an excellent release. If not, there is a tendency for the implant to get caught up at the plunger tip.

IDOSE TR

The newest entrant to this novel procedural pharmaceutical devices space is the iDose TR (Glaukos), an intracameral SR implant designed to deliver a proprietary formulation of the prostaglandin analog, travoprost. Approved by the FDA in December 2023, the device measures 1.8 mm x0.5 mm and comprises three main parts: a drug reservoir, elution membrane and scleral anchor (Figure). The device is placed into the anatomical drain of the eye at the site of the trabecular meshwork, delivering medication to the target tissues.

CLINICAL DATA FOR IDOSE

The prospective, three-arm, double-masked, multi-center Phase 2 and 2b studies of 154 subjects assessed the implant for safety and preliminary efficacy in reducing elevated IOP. Single administration of two iDose models with different release rates was compared to sham surgery plus topical timolol b.i.d. Patients were randomized (iDose fast release, n = 51; iDose slow release, n = 54; timolol, n = 49). Phase 2b continued the study with additional assessments every 3 months through 36 months. Subjects had mild to moderate open-angle glaucoma or ocular hypertension on zero to three IOP-lowering medications at screening. IOP was measured at 8 am, 10 am, and 4 pm. Baseline diurnal IOP ranged from 21 to 36 mm Hg.

The travoprost implant met a primary endpoint of IOP-lowering efficacy non-inferior to timolol at 3 months. IOP change from baseline was statistically significant at all visits for all treatment groups6 with IOP lowering sustained over 36 months. At month 12, 58%, 92% and 86% of study eyes were well controlled on the same or fewer IOP-lowering topical medications in the timolol 0.5% b.i.d., fast-eluting (FE) and slow-eluting (SE) travoprost iDose treatment groups, respectively. Even after 36 months, more than 60% of eyes in the travoprost iDose groups were still well controlled on the same or fewer topical medications. For the timolol b.i.d. group, 2,190 eyedrops were administered over 3 years per eye compared with a single administration of the iDose device for the sustained- release travoprost groups.

The most common ocular adverse events (AEs) for the iDose groups (FE/SE) were cataract (7.8%/5.6%), reduced visual acuity (5.9%/7.4%) and eye pain (7.8%/0%). No ocular AEs had an incidence >2.0% in the timolol group.

Two identically-designed Phase 3, parallel-group, double-masked, randomized, sham-controlled trials were conducted comparing two models of travoprost iDose (TII, fast eluting and slow eluting) to topical timolol (0.5%) b.i.d. (GC-010 and GC-012). The primary outcome measures were the mean change from baseline IOP in the study eye compared to timolol at 8 a.m. and 10 a.m. at Day 10, Week 6 and Month 3. Secondary outcome measures included the mean change from baseline IOP compared to timolol at 12 months. A total of 1,150 subjects were included. Both travoprost-eluting implants achieved non-inferiority to topical timolol through 3 months, the pre-specified primary efficacy endpoint.

In addition, following a 4-week prostaglandin (PGA) washout, IOP rose by an average of 
5.8 mm Hg above those levels observed at screening. After TII insertion, IOP decreased by an average of 7.1 mm Hg. These data demonstrated that a single TII resulted in significantly greater (by 1.3 mm Hg) IOP lowering vs daily PGA administration pre-study
(P = 0.0003).

At 12 months, 93% of the TII compared with 67% of the timolol 0.5% b.i.d. subjects in the Phase 3 studies were well controlled on the same or fewer IOP-lowering topical medications, and 81% of TII subjects were completely free of IOP-lowering topical medications. Tolerability was favorable with 98% of the slow release TII subjects continuing at 12 months. Endothelial cell density was stable over 12 months in both treatment groups. 

The iDose Exchange Study, a prospective, multi-center trial to evaluate the safety of the exchange procedure, involved 33 subjects previously implanted with slow-release TII from the Phase 2b study. Each subject’s study eye underwent a surgical exchange with the slow-release TII model. The average total extended evaluation period was more than 5 years. No clinically meaningful changes in corneal endothelial cell counts were observed.

IDOSE TR IN THE CLINIC 

My pearls for patient selection for the iDose:
1. Similar to Durysta, consider patients who have deeper anterior chamber space, such as those with pseudo phakic status.
2. Beyond seeking to reduce IOP, other quality of life issues should be considered where sustained release would be a better approach than topical therapy. These include but are not limited to decreasing side effects and cost of topical therapy.

Now for my iDose insertion tips:
1. Similar to any other MIGS therapy, it is critical to ensure proper view of the anatomical landmarks. However, actual placement of the iDose needs to be into only the scleral wall to achieve successful implantation.
2. After insertion of the implant, it is important to test that it stays in place. This is done by touching the insert a few times. This prevents any disinsertion of the implant in the post-procedure period. 

CONCLUSION

Barriers to treatment compliance have long posed a stubborn, formidable problem for glaucoma specialists seeking to preserve their patients’ vision. Newly available innovations such as Durysta and iDose, however, with more in the pipeline, could help us overcome many of those barriers once and for all. In addition to preserved vision, patients will benefit from less ocular surface irritation and disease. OM

References 

1. Radcliffe NM, Shah M, Samuelson TW. Challenging the “topical medications-first” approach to glaucoma: a treatment paradigm in evolution. Ophthalmol Ther. 2023;12(6):2823-2839.
2. The American Academy of Ophthalmology. Primary Open-Angle Glaucoma Preferred Practice Pattern. San Francisco, CA, 2020.
3. Moore SG, Richter G, Modjtahedi BS. Factors affecting glaucoma medication adherence and interventions to improve adherence: a narrative review. Ophthalmol Ther. 2023;12(6):2863-2880.
4. Dreer LE, Girkin CA, Campbell L, Wood A, Gao L, Owsley C. Glaucoma medication adherence among African Americans: program development. Optom Vis Sci. 2013;90(8):883-897.
5. Sirinek PE, Lin MM. Intracameral sustained release bimatoprost implants (Durysta). Semin Ophthalmol. 2022;37(3):385-390.
6. Berdahl JP, Sarkisian SR Jr, Ang RE, Doan LV, Kothe AC, Usner DW, Katz LJ, Navratil T; Travoprost Intraocular Implant Study Group. Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension. Drugs. 2023 Dec 7. Epub ahead of print.
7. Mylla Boso AL, Gasperi E, Fernandes L, Costa VP, Alves M. Impact of ocular surface disease treatment in patients with glaucoma. Clin Ophthalmol. 2020;14:103-111.
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9. Mastropasqua L, Agnifili L, Mastropasqua R, Fasanella V. Conjunctival modifications induced by medical and surgical therapies in patients with glaucoma. Curr Opin Pharmacol. 2013;13(1):56-64.
10. DI Staso S, Agnifili L, Cecannecchia S, DI Gregorio A, Ciancaglini M. In Vivo Analysis of Prostaglandins-induced Ocular Surface and Periocular Adnexa Modifications in Patients with Glaucoma. In Vivo. 2018;32(2):211-220.
11. S DIS, Agnifili L, Ciancaglini M, Murano G, Borrelli E, Mastropasqua L. In Vivo Scanning Laser Confocal Microscopy of Conjunctival Goblet Cells in Medically-controlled Glaucoma. In Vivo. 2018;32(2):437-443.
12. Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29(6):618-621.
13. Schweitzer JA, Hauser WH, Ibach M, et al. Prospective Interventional Cohort Study of Ocular Surface Disease Changes in Eyes After Trabecular Micro-Bypass Stent(s) Implantation (iStent or iStent inject) with Phacoemulsification. Ophthalmol Ther. 2020;9(4):941-953.
14. Stringham J, Ashkenazy N, Galor A, Wellik SR. Barriers to glaucoma medication compliance among veterans: dry eye symptoms and anxiety disorders. Eye Contact Lens. 2018;44:50-54.
15. Nouri-Mahdavi K, Hoffman D, Coleman AL, et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111:1627-1635.

Savak “Sev” Teymoorian, MD, MBA, is a glaucoma specialist at Harvard Eye Associates, Laguna Hills, Calif. Contact him at steymoorian@harvardeye.com. Disclosure: Dr. Teymoorian is a consultant to Allergan, an Abbvie Company, and Glaukos.