Adding to the evolving glaucoma treatment landscape, researchers recently detailed the advancements in interventional glaucoma therapy that suggest leveraging various treatment modalities early in the disease course may enhance intraocular pressure control and improve long-term outcomes.

For over 150 years, topical medications have been the primary treatment for glaucoma. However, limitations such as nonadherence and ocular surface disease impact their real-world effectiveness. New interventions—including selective laser trabeculoplasty (SLT), minimally invasive glaucoma surgeries (MIGS), and procedural pharmaceuticals—are gaining traction as alternatives or adjuncts to traditional therapies.

This paradigm shift emphasizes comprehensive intraocular pressure (IOP) control by targeting multiple mechanisms, including trabecular and uveoscleral outflow, aqueous suppression, and episcleral venous pressure, the researchers—led by J. Morgan Micheletti, MD, FACS, of the Berkeley Eye Center in Texas—described in their Ophthalmology and Therapy article. A combination of these approaches is often required to achieve sufficient IOP reduction and minimize disease progression.

Historically, glaucoma management has followed a sequential approach, in addition to monotherapy; first, initiating treatment with a single topical medication and then progressing to additional therapies as needed. The problem with this approach, the researchers of this review wrote is, “a reactive approach may lead to step-wise treatment advancement often only after incremental progression has occurred: patients have to get worse to get the treatment they need to control their disease.”

Studies such as the Ocular Hypertension Treatment Study (OHTS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS) highlighted that a significant proportion of patients require multiple medications to achieve target IOP levels.

Similarly, monotherapy with SLT or trabeculectomy may provide initial efficacy but often requires retreatment. For example, the researchers cited the LiGHT trial, which found that 37.3% of patients undergoing primary SLT required at least one additional laser treatment over six years. In the Advanced Glaucoma Intervention Study (AGIS), nearly half of patients who underwent initial laser therapy later required trabeculectomy.

Glaucoma therapy aims to balance aqueous humor production and outflow, which can be targeted through mechanisms such as

• Aqueous suppression using beta-blockers and carbonic anhydrase inhibitors 
• Trabecular outflow enhancement with SLT and MIGS to facilitate drainage through the trabecular meshwork
• Uveoscleral outflow enhancement with prostaglandin analogs that can improve alternative drainage pathways.

Multimechanism therapy involves combining treatments that address these pathways to optimize IOP control. Indeed, a recent study found that patients undergoing MIGS with concurrent topical therapy experienced significant and sustained IOP reduction over 4 years, the researchers cited from the current literature. “Even drugs that act on the same aspect of IOP regulation can provide synergistic effects in lowering IOP,” they wrote.

“Comprehensive IOP control can be achieved with reductions in both mean IOP and IOP fluctuations, the latter of which may be a significant independent risk factor for disease progression,” the researchers explained further. “Utilization of SLT, procedural pharmaceuticals, and MIGS can minimize or eliminate the need for daily self-dosing of topical medications, providing a potential drop-free lifetime of therapy that leads to greater patient satisfaction. Such an approach may also be cost-effective over time. For instance, lens extraction effectively lowers IOP and medication burden in eyes with glaucoma, yet multiple studies demonstrate that combining phacoemulsification with MIGS is more cost-effective than phacoemulsification alone by reducing ongoing medical therapy and further interventions.”

They also described elements of patient safety that can be addressed with multimodal, multi-mechanism approaches. When MIGS is combined with cataract surgery, for example, they wrote, surgeons can “improve IOP control with minimal or no incremental risk” to patients. 

This approach represents the best chance to prevent glaucoma progression over time, they concluded. 

A full list of the authors' conflict of interest disclosures can be found in the published research.