Glaucoma specialists take back treatment compliance

The medication-first approach to glaucoma has been a standard of care for decades. But as global populations increase, an interventional, surgical-first approach is necessary. That’s the argument made by Leon Au, MBBS, BSc, FRCOphth, in his presentation at the European Glaucoma Society Congress in Dublin, Ireland, in June 2024.

OCT, optical coherence tomography; RNFL, retinal nerve fibre layer

He argued that the existing treatment modalities for glaucoma could do more harm than good and place too much of the treatment burden on patients’ adherence. Interventional approaches to glaucoma management could radically change the future of care for an ever-increasing patient population (Figure 1).

Why aren’t surgeons using MIGS?

To illustrate the disparity between the availability of minimally invasive glaucoma surgery (MIGS) devices and their use cases, Mr Au shared figures which represent the device market. Many eyes are “left behind” by surgical glaucoma care, Mr Au said, because surgeons do not implement MIGS devices effectively.

Currently, only 10% of MIGS devices indicated for standalone use are implemented in stand-alone procedures. Around 90% of MIGS utilisation remains in the combined glaucoma-cataract surgery setting (Figure 2).

Mr Au pointed out that in some cases, an outdated attitude toward ocular surgery could be influencing ophthalmologists’ perceptions of MIGS interventions. In the case of trabeculectomy, for example, the procedure is invasive, time-consuming and difficult to perform, and is associated with extended recovery time and potential for complications that may leave patients hesitant.

That is not to say this is not a suitable procedure for certain patients; rather, traditional surgeries such as trabeculectomy should be regarded as totally separate procedures from the device-driven MIGS therapies available to patients now. A heavy reliance on topical medications¹ also persists, despite developments in the glaucoma space, with topical treatments maintaining dominance of the glaucoma market.

Compliance is key

Two US studies Mr Au cited highlight the responsibility and drastic consequences of glaucoma medication compliance. The first, a retrospective cohort study using health insurance claims data, found that nearly 50% of patients discontinued use of the medications within 6 months of the prescription, and more than 90% of patients were not adherent with medication usage.² In the second study, a long-term study in Olmsted County, Minnesota, sponsored by the National Institutes of Health, investigators assessed disease progression in patients with primary open-angle glaucoma (POAG) over a period from 1965 to 2000.³ Residents of Olmsted County diagnosed with POAG between 1965 and 1980 received follow up through the end of 1995; these patients’ records were pooled with newly collected data for participants diagnosed with POAG from 1981 to 2000, with follow up through the end of 2009.

Reviewing the dataset, Mr Au summarised, “Despite [patients] being diagnosed and treated with topical glaucoma medication, the probability of disease progression leading to blindness in at least one eye [was] shown to be 13.5%, and 4.3% bilaterally.” In addition, he said, average time to blindness among these patients following diagnosis was 5.8 years.³ Though topical treatments can have a high efficacy rate, he said, “Drops are only effective if they’re taken, and a high proportion of patients are not taking them.”

There are a number of reasons patients may choose to discontinue use of topical glaucoma management drops. Dry eye disease associated with ocular drops is a noteworthy adverse effect for many patients. The symptoms of dry eye are magnified in instances of combined, or “stacked,” topical drops.⁴ In one study Mr Au cited, around 51% of patients with glaucoma who used one topical drop experienced dry eye disease. That percentage grew to 55% for patients on two types of topical drop, and 60% for patients using three or more drops.⁵

Further, while many patients experienced positive change in glaucoma symptoms after they began using one ocular drop, adding more topical antiglaucoma medications to the regimen did not increase efficacy of treatment. Mr Au described a diminishing return on efficacy and safety following the addition of third and fourth topical medications.¹ This is significant, as approximately 22% of patients with glaucoma are prescribed three or more topical medications.⁶

SLT, selective laser trabeculoplasty; MIGS, minimally invasive glaucoma surgery; MIBS, minimally invasive bleb surgery.

Quality over quantity

Currently, the treatment paradigm for glaucoma addresses surgical intervention as a “last resort,” Mr Au said (Figure 3A). Patients may be encouraged to use three or more topical medications before surgical intervention is explored. Medications will also be used as other therapies are implemented, Mr Au said; as a result, many clinicians view the treatment paradigm as “medications first and always.”

Following a plateau or diminishing in efficacy of topical treatment, patients are typically presented with surgical options such as selective laser trabeculoplasty (SLT). In most cases, Mr Au said, SLT is paired with continuation of topical medications, or new topical medications, as indicated by the patient’s post-surgical needs. Filtration surgery is the “next step” on the path, with an aqueous shunt or other MIGS device implantation being treated as the final attempt at glaucoma management. This approach, Mr Au noted, limits treatment efficacy due to long recovery periods, increased risk of complication and heightened failure rates.

Along with dry eye and ocular discomfort, other quality-of-life factors support earlier MIGS-lead interventions, Mr Au said. One analysis of patients with POAG who participated in the iStent inject clinical trial (Glaukos) gauged performance in the Visual Function Questionnaire 25 (VFQ-25) and Ocular Surface Disease Index (OSDI).⁷ Investigators recorded responses from patients in two groups: those who underwent standalone cataract surgery and those who underwent cataract surgery and received implantation of the iStent inject in a combined procedure. Across a 24-month follow-up period, patients who underwent the combined glaucoma procedure responded with patient-reported outcomes which had higher composite scores on both the VFQ-25 and OSDI. In particular, patients who underwent the combined glaucoma and cataract procedure reported higher scores in quality-of-life subscales including general vision, ocular pain, near and distance activities, peripheral vision and mental health outcomes.

What would an idealised, MIGS-focused treatment paradigm look like? According to Mr Au, it would begin with SLT as the first step, adopting drug delivery after surgery as a supplement or “bridge therapy” as needed (Figure 3B). From there, if the patient still needed surgery, MIGS and minimally invasive bleb surgery (MIBS) could be considered. In severe cases of glaucoma, MIBS would be the next step, before additional filtration surgeries were considered.

A perfect storm

Mr Au described the looming promise of an aging population and increased glaucoma diagnosis rates as a “perfect storm.” By the year 2050, 19% of the global population is expected to be over 60 years old. With an increasingly aged population comes increased prevalence of glaucoma. Globally, glaucoma rates increase drastically at age 70, with the most significant age-related increases seen among patients in Latin America and the Caribbean.⁸

The prevalence of POAG is expected to increase by 8.6% between 2020 and 2026, and diagnosis rates will increase even more quickly than prevalence rates.⁹ Under these circumstances, adopting an interventional approach to glaucoma is crucial to preserve both vision and quality of life for millions of people around the world.

References

1. Johnson TV, Jampel HD. Intraocular Pressure Following Prerandomization Glaucoma Medication Washout in the HORIZON and COMPASS Trials. Am J Ophthalmol. 2020;216:110-120. doi:10.1016/j.ajo.2020.04.008

2. Malihi M, Moura Filho ER, Hodge DO, Sit AJ. Long-term trends in glaucoma-related blindness in Olmsted County, Minnesota. Ophthalmology. 2014;121(1):134-141. doi:10.1016/j.ophtha.2013.09.003

3. Nordstrom BL, Friedman DS, Mozaffari E, Quigley HA, Walker AM. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140(4):598-606. doi:10.1016/j.ajo.2005.04.051

4. Rossi GC, Tinelli C, Pasinetti GM, Milano G, Bianchi PE. Dry eye syndrome-related quality of life in glaucoma patients. Eur J Ophthalmol. 2009;19(4):572-579. doi:10.1177/112067210901900409.

5. Erb C, Gast U, Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol. 2008;246(11):1593-1601. doi:10.1007/s00417-008-0881-9.

6. Report: 2022 Glaucoma Device Market Report | Market Scope. Published 2022. Accessed July 2024.

7. Samuelson TW, Singh IP, Williamson BK, et al. Quality of Life in Primary Open-Angle Glaucoma and Cataract: An Analysis of VFQ-25 and OSDI From the iStent inject® Pivotal Trial. Am J Ophthalmol. 2021;229:220-229. doi:10.1016/j.ajo.2021.03.007

8. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013.

9. Report: 2021 Glaucoma Device Market Report | Market Scope. Published 2021. Accessed July 2024.

Leon Au, MBBS, BSc, FRCOphth | E: leonau01@me.com

Au is a consultant ophthalmologist at Manchester Royal Eye Hospital in England. He specialises in the field of glaucoma and cornea.
Financial disclosures: Lectures and consultancy, Glaukos.