Glaucoma is the leading cause of irreversible blindness across the globe.1 Although the pathophysiology of glaucoma is varied, the modern treatment paradigm remains focused on the reduction of IOP, the only modifiable risk factor associated with the progression of disease.2 The reduction of IOP has traditionally been achieved by pharmacology, laser therapy and surgery.3,4 The treatment landscape has evolved considerably in recent years, particularly with the advent of minimally invasive glaucoma surgery (MIGS).5,6 Furthermore, novel medical therapies have been introduced and broadened the range of available topical glaucoma drops. This review aims to provide an update on new pharmacologic options that are either currently available or undergoing clinical trials.
Omidenepag isopropyl
Omidenepag isopropyl (Omlonti, Visiox) 0.002% is a relatively selective prostaglandin E2 receptor agonist that increases aqueous outflow through both the conventional (trabecular meshwork) and unconventional (uveoscleral) pathways via a novel first-in-class mechanism of action. It received FDA approval in September 2022. Phase 3 clinical trials7,8 showed that omidenepag isopropyl lowered IOP by 4-6 mmHg. It not only was noninferior to timolol, but also provided an IOP lowering effect for patients who respond poorly to traditional prostaglandin analogues (PGAs). Its efficacy and side effect profile were similar to those of other PGAs.9 This novel drug is a great option for patients who failed a PGA before switching to another class.
Sepetaprost
Sepetaprost 0.002% (Santen Pharmaceutical Co.) is a prodrug (a compound that has no pharmacologic activity but is converted into an active drug in the body through chemical or enzymatic reactions) that targets the prostaglandin FP and EP3 receptors. Unlike traditional PGAs that target only the FP receptor, sepetaprost also works on EP3, potentially providing additional efficacy.10 The phase 2 clinical trial showed that although sepetaprost’s IOP lowering effect was similar to that of latanoprost, around 6-7 mmHg, it had a lower incidence of adverse events.11 Another phase 2 study presented at AAO showed that sepetaprost was noninferior to timolol for patients with primary open angle glaucoma and ocular hypertension.12 Similar to omidenepag isopropyl, sepetaprost is another option in the first-line PGA class that provides patients with another opportunity to remain on a single drop before adding a second class.
NCX 470
NCX 470 (Nicox SA) is a nitric oxide (NO) donating bimatoprost eyedrop that targets not only the uveoscleral pathway via prostaglandin receptors, but also the conventional pathway via NO-related relaxation of the trabecular meshwork. The first product of its kind was latanoprostene bunod, which has been shown to have a slightly increased IOP lowering effect compared to latanoprost.13 Phase 2 and 3 clinical trials suggest that NCX 470 also lowers IOP better than either latanoprost or bimatoprost alone, with around 9 mmHg of reduction.14,15,16 This drug is another alternative option to the two previously discussed, harnessing NO to provide a dual mechanism of action.
What technicians and staff should know when it comes to glaucoma treatments
Given the explosion of new glaucoma treatments, we recommend technicians to familiarize themselves with the different types becoming available, their pros and cons, and their prescribing process. Having a basic understanding of these therapies will help technicians better answer patient questions, especially when they ask how this new medication differs from ones they have previously used. We know that comprehension increases patient compliance for glaucoma drug regimens.
All new treatments face prescribing hurdles in the beginning stages, like lack of insurance coverage, prior authorizations, and low company support. Learning to navigate these issues beforehand can streamline the process when providers are actually prescribing these treatments. For each treatment that the providers are interested in using, we recommend that technicians and staff investigate their insurance coverages, pharmacy availability, and other logistics ahead of time. Lastly, we encourage technicians and staff to be advocates for their patients by being aware of new developments in the field of glaucoma and discussing them with the providers.
QLS-101
QLS-101 (Qlaris Bio) is a novel drug that lowers IOP by widening the aqueous outflow channels, especially the episcleral vessels, by modulating adenosine triphosphate-sensitive potassium channels. This episcleral venous pressure (EVP)-lowering effect has been supported by early animal studies;17,18 human trials are currently ongoing. The ability to decrease EVP is an attractive option for glaucoma patients who are progressing despite an apparently controlled IOP, especially those with normal tension glaucoma or high EVP (ie, Sturge-Weber syndrome). QLS-101 has the potential to lower IOP even further for these patients whose IOP is often are already in the mid-teens. Nevertheless, further research in humans is needed to truly assess its effects.
iDose TR
Following on the heels of the Durysta bimatoprost implant (AbbVie), which ushered in the era of sustained-release drug delivery in glaucoma, the new iDose TR (Glaukos) was approved in late 2023. The implant is a microscopic titanium container that is anchored to the scleral wall through the trabecular meshwork, eluting 75 µg of travoprost across a nanoporous membrane into the anterior chamber. Phase 2 and 3 clinical trials showed that iDose was noninferior to timolol, lowering IOP by 6-7 mmHg up to 3 years.19,20,21 Most study participants (70%) were controlled on the same or fewer number of drops at 3 years, compared to 45% in the timolol group.19 It had an overall positive safety profile, with no significant changes to corneal endothelial cell density.20,21 Although this device requires an operating room procedure, the long-term convenience outweighs the initial time investment. It is an especially attractive option for patients who struggle with eyedrop compliance or side effects.
Bimatoprost contact lens (LL-BMT1)
LL-BMT1 (MediPrint Ophthalmics) is a bimatoprost and hyaluronic acid eluting contact lens currently under investigation. A recent press release from the American Academy of Optometry 2024 meeting regarding phase 2b results showed that participants only needed to change their contacts biweekly over the course of 3 weeks to achieve an IOP lowering efficacy like the bimatoprost 0.01% eyedrop.22 Additionally, patients reported a 40% improvement in dry eye symptoms, likely from the hyaluronic acid component. This device occupies a new unique niche in glaucoma treatment, offering to target both IOP reduction and dry eye, perhaps even combining a refractive component if the contact lens were to have built-in correction.
Nicotinamide and pyruvate
Research into neuroprotective options has accelerated over the past decade, with special attention on nicotinamide and pyruvate. Basic science research suggests that retinal ganglion cell vulnerability is influenced by low nicotinamide adenosine leotide (NAD), such that oral supplementation with NAD might provide a protective effect against further glaucomatous damage.23,24 A 2023 cross-sectional study suggests that niacin intake was associated with a decreased risk of glaucoma,25 while a 2022 phase 2 clinical trial showed that nicotinamide and pyruvate combination supplementation provided small, short-term improvement in visual field pattern standard deviation.26 The phase 3 clinical trial is currently underway, much to the excitement of the glaucoma community, as a true neuroprotective agent has been a significant goal for decades.
NT-501 ciliary neurotrophic factor implant
Ciliary neurotrophic factor (CNTF) has strong preclinical evidence for improving optic nerve axon regeneration and retinal ganglion cell survival.27 The NT-501 is a CNTF-eluting intravitreal implant that was recently shown by a small phase 1 trial to not only be safe, but also potentially improve visual field index and retinal nerve fiber layer thickness after 3 months.28 These encouraging results will be further evaluated in an ongoing phase 2 clinical trial.
Conclusion
The treatment landscape of glaucoma is undergoing explosive change, with not only new IOP lowering drug options on the horizon, but also potential neuroprotective options that can potentially restore some of what was previously thought to be irreversible damage. These advances portend a hopeful future in which we can better address this leading cause of irreversible blindness. OP
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The authors report no relevant disclosures
