With insights from prominent clinicians and researchers, explore the forefront of recent glaucoma research—from groundbreaking trials to emerging trends
In our pursuit to provide optimal care for glaucoma patients, research plays a pivotal role. This article explores the latest advancements and perspectives from top experts, shedding light on impactful studies and future directions in glaucoma care.
Without research, we cannot advance in our quest to provide the best possible care and outcomes for our patients. Fortunately, we live in an era of rapid advancement, witnessing significant shifts in the way we can provide care for our glaucoma patients. By uncovering new targets and earlier detection and intervention, we aim not only to halt deterioration but also to restore vision.
Current landscape of glaucoma clinical trials
The hot topic in glaucoma for decades now has been all about minimally invasive glaucoma surgeries (MIGSs). MIGS has become an essential modality for glaucoma management, fulfilling the promise of safe and efficacious early interventions for mild-to-moderate glaucoma patients, leaving them with minimal trauma and enabling rapid recovery.
More recently, researchers are revisiting MIGS, exploring ways to further enhance outcomes. Combined MIGS procedures, whether targeting the same aqueous outflow mechanism or a different one, have faced challenges due to limited high-quality evidence supporting their effectiveness and associated costs. Of course, having more options to offer patients increases the opportunity to find the best therapeutic option to meet their individual needs.
The latest exciting innovations to limit vision loss in glaucoma patients are the minimally invasive micro sclerostomy (MIMS) and trabeculotome tunneling trabeculoplasty (Triple-T), which have presented promising results in early trials and great potential for clinical application.
Despite our focus on controlling elevated IOP as our primary modifiable risk factor, we recognize glaucoma as a multifactorial neurodegenerative disease. Researchers are now looking at targeting those neurodegenerative processes that occur at the retinal ganglion cell level, leaning into neuroprotective strategies directed at the degenerative mechanisms, metabolism, insulin signaling, mTOR, axon transport, apoptosis, autophagy, and neuroinflammation.
Despite exciting and interesting initial results, the variability and complexity of glaucoma have highlighted the need for strict phenotyping of patients to translate current preclinical findings into a clinical setting.
Devices, interventions, and therapeutics—numerous clinical trials are ongoing at every phase of development, while others have overcome regulatory hurdles and are now in prime time, available at clinics near you.
Expert perspectives on recent and future glaucoma studies
We asked expert clinicians, who are also deeply engaged in research, to share their opinions and key insights about the studies they are most excited about and those they see as among the most impactful to glaucoma care—both recently and in the years to come.
Dr. Steven J. Gedde, a professor of ophthalmology and vice chair of education at the Bascom Palmer Eye Institute, as well as an investigator in numerous clinical trials, recognizes the importance of well-designed randomized studies.
“Several recent multicenter randomized clinical trials have provided valuable information to guide the care of patients with glaucoma,” Dr. Gedde shared. “Randomized clinical trials are considered the gold standard for evaluating therapies. The process of randomization is designed to produce comparison groups that differ only by the treatment received.”
Importantly, we also wanted to be sure that we understand the challenges encountered when implementing new therapies, technologies, or policies into practice.
Dr. Jason Bacharach is the medical and research director at North Bay Eye Associates and co-director of Glaucoma Service in the Department of Ophthalmology at the California Pacific Medical Center and Pacific Vision Eye Institute. He has been at the forefront of clinical trials for decades.
He shared that with every completed trial and presentation of data, there are things that should be carefully considered. “The question of translation from trials to practice is key. Look at the conduct of the trial. How long were the subjects followed? How large was the trial? Was there a control wing?” he said.
He added that the enrolled patient population may differ from many of the patients currently sitting in the waiting room. “One important factor is to ensure the representative population in the trial is reflective of the patients you care for,” he added.
Perspectives on the PTVT study
Dr. Gedde provided his thoughts on three clinical trials that hold great potential and opportunity for the future of glaucoma care. The first is the Primary Tube Versus Trabeculectomy (PTVT) Study, which compared the safety and efficacy of tube shunt implantation and trabeculectomy with mitomycin C (MMC) as an initial glaucoma surgical procedure.1
“The trial enrolled 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery,” Dr. Gedde shared. “They were randomly assigned to treatment with a tube shunt (350-mm2 Baerveldt glaucoma implant) or trabeculectomy with MMC (0.4 mg/ml for 2 minutes).”
This trial followed patients for up to five years. “Primary tube shunt surgery had a higher failure rate than primary trabeculectomy with MMC throughout five years of follow-up, but the difference was only statistically significant at one year but not at three years or five years. Mean IOPs were lower in the trabeculectomy group than the tube group, and this superior IOP reduction was achieved with significantly fewer medications,” he said.
“Early postoperative complications were more common after trabeculectomy with MMC compared with tube shunt surgery, but both procedures had similar rates of late postoperative complications and serious complications requiring reoperation to manage the complication and/or producing vision loss,” Dr. Gedde continued. “An inverse relationship was seen between preoperative IOP and surgical failure in the tube group; patients with lower preoperative IOP had higher failure rates, and those with higher preoperative IOP had lower failure rates. The success of trabeculectomy with MMC was less influenced by preoperative IOP.”
Dr. Gedde shared the impact of the PTVT study and the importance of patient selection. “This study highlights the importance of considering preoperative IOP when deciding between primary trabeculectomy with MMC and primary tube shunt surgery,” he noted.
Insights from the EAGLE trial
Next, Dr. Gedde shared his insights into the Effectiveness in AngleClosure Glaucoma of Lens Extraction (EAGLE) Trial, which compared clear lens extraction and laser peripheral iridotomy (LPI) as initial treatment for primary angle-closure disease.2
“The study recruited 419 patients age ≥ 50 years with newly diagnosed primary angle-closure glaucoma or primary angle closure with IOP ≥ 30 mmHg. Enrolled patients were randomized to clear lens extraction or LPI,” Dr. Gedde shared.
Nearly all outcome measures favored the clear lens extraction group after three years, including quality of life, IOP, use of glaucoma medications, and visual acuity.
“A cost analysis was performed based on patients recruited at centers in the United Kingdom,” he said. “The initial cost was higher among patients who underwent clear lens extraction relative to LPI, but lens extraction was more cost-effective after 10 years due to lower medication usage and fewer subsequent ocular procedures.”
Dr. Gedde also provided his impression of the EAGLE trial. “This important trial demonstrated the benefit of early lens extraction in a subset of patients with primary angle-closure disease, i.e., those with primary angle-closure glaucoma and primary angle closure with marked IOP elevation.”
This shift, we noted, where interventional glaucoma, including laser treatment, surgery, and innovative drug delivery systems to lower IOP, should no longer be thought of as an aggressive approach or a last resort. Instead, it should be seen as an opportunity to minimize the treatment burden for patients and enhance their long-term outcomes.
This opportunity for first-line intervention was highlighted by Dr. Gedde as he shared his thoughts on the recent Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial. This multicenter randomized clinical trial compared eye drops and selective laser trabeculoplasty (SLT) as first-line treatments for reducing IOP.3
A total of 718 patients with newly diagnosed, untreated open-angle glaucoma and ocular hypertension were randomly assigned to treatment with 360 degrees of SLT or topical glaucoma medications.
Dr. Gedde described the key results of the LiGHT Trail. “Nearly 80% of patients maintained IOP control with only SLT during years of follow-up, and a significant cost benefit of SLT over drops was observed,” he shared. “There was no significant difference in quality of life between the drop group and SLT group, and this was the primary outcome measure in the study. An extension study continued the follow-up of patients from the LiGHT Trial for six years. The rate of glaucomatous progression and need for trabeculectomy surgery was significantly higher in the drop group compared with the SLT group,” he explained.
His final thought: “This landmark trial supports the use of SLT as an initial treatment for open-angle glaucoma and ocular hypertension.”
AI in glaucoma: A work in progress
The wave of artificial intelligence (AI) and its applications are permeating many aspects of our lives, some of which we don’t even realize. AI has established itself as a valuable tool across many specialties within ophthalmology, holding the potential to standardize and improve disease detection for earlier diagnosis and intervention. It can also play a crucial role in monitoring therapeutic outcomes and improving access to screening.
Dinah Chen and colleagues recently published a review of AI and deep learning applications in glaucoma. They found that, while interesting and promising, more work is needed before this research study is ready to roll into our clinics. Specifically, they noted that most of the algorithms are limited by their focus on a single imaging modality, fundus photos or optical coherence tomography, and the lack of a consensus in diagnostic criteria.4
Chen and colleagues also felt that an AI algorithm predicting treatment response was still a gap that needed to be addressed. These are all crucial issues, given the complexities inherent in the multimodal and variable nature of glaucoma. For now, we will categorize AI under ‘to be continued.’
There never seems to be a shortage of glaucoma patients in our waiting rooms each day, with the burden of delivering timely and quality care always top of mind. The experience of the pandemic may have spurred it on, but virtual glaucoma clinics have taken a significant step forward in recent years. And why not? They hold the potential to increase healthcare capacity while easing the disease burden of glaucoma for both patients and physicians.
Yi Fang Lee and colleagues in Singapore published an evaluation of the outcomes of their asynchronous virtual glaucoma clinic after three years of experience.5 More than 3,400 patients had their visual acuity, intraocular pressure (IOP), and visual fields or optic nerve head imaging recorded, followed by a virtual review by an ophthalmologist. They found that overall, this model was safe, time-efficient, and cost-effective, with patients experiencing low rates of glaucoma progression.
A guiding principle in glaucoma innovation
Advancements are indeed exciting,often launched at flashy eventsduring conferences. However, it isimportant to ask how they will fit intoour daily practice, workflow, and forour staff and patients.
Dr. Bacharach raises some key thingsfor pharma and device companies toconsider when introducing somethingnew into the glaucoma space, hopingfor uptake into practices. “Ask,what is the value proposition of theintellectual property (IP)? Will the IPbe disruptive, create new revenuestreams, have a billable code or atleast make fiscal sense if approved?”he said.
But most importantly, he added, thequestion to always keep top of mindwhen moving from experimental andinto clinical practice is, “Will it improvethe quality of life of patients?”
Traditionally, glaucoma hasbeen managed primarily as amedical disease, with surgicalintervention consideredonly when things start todeteriorate. However, thereis a paradigm shift happening.The idea of harnessingtechnology, combined withadvancements in therapy andexploration of new targets, has led usto an exciting time for clinicians and ahopeful time for patients.
References
- Gedde SJ, Feuer WJ, Lim KS, Barton K, Goyal S, Ahmed II, Brandt JD; Primary Tube Versus Trabeculectomy Study Group. Treatment Outcomes in the Primary Tube Versus Trabeculectomy Study after 5 Years of Follow-up. Ophthalmology. 2022;129(12):1344-1356.
- Mitchell WG, Azuara-Blanco A, Foster PJ, Halawa O, Burr J, Ramsay CR, Cooper D, Cochran C, Norrie J, Friedman D, Chang D. Predictors of long-term intraocular pressure control after lens extraction in primary angle closure glaucoma: results from the EAGLE trial. Br J Ophthalmol. 2023;107(8):1072-1078.
- Gazzard G, Konstantakopoulou E, Garway-Heath D, Adeleke M, Vickerstaff V, Ambler G, Hunter R, Bunce C, Nathwani N, Barton K; LiGHT Trial Study Group. Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension. Ophthalmology. 2023;130(2):139- 151
- Chen D, Ran Ran A, Fang Tan T, Ramachandran R, Li F, Cheung CY, Yousefi S, Tham CCY, Ting DSW, Zhang X, Al-Aswad LA. Applications of Artificial Intelligence and Deep Learning in Glaucoma. Asia Pac J Ophthalmol (Phila). 2023;12(1):80-93.
- Lee YF, Chay J, Husain R, Wong TT, Ho CL, Lamoureux EL, Chew ACY. Three-year Outcomes of an Expanded Asynchronous Virtual Glaucoma Clinic in Singapore. Asia Pac J Ophthalmol (Phila). 2023;12(4):364-369.
Editor’s Note: A version of this article was first published in CAKE Magazine Issue 22.
