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Disease-modifying glaucoma drugs · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: Introduction.
• 0:00
  SPEAKER_00: Glaucoma is a chronic eye disease where nerve cells in the retina and optic nerve gradually die, often causing blindness if untreated.
• 0:09
  SPEAKER_00: For decades, the main proven treatment has been lowering intraocular pressure, IOP, the fluid pressure inside the eye, to slow damage.
• 0:18
  SPEAKER_00: This is done with eye drops, laser, or surgery.
• 0:21
  SPEAKER_00: But pressure isn't the whole story.
• 0:23
  SPEAKER_00: Many patients still lose vision even when their pressure is well controlled.
• 0:27
  SPEAKER_00: In fact, about one-third of treated patients eventually go blind in one eye, and some people, so-called normal tension glaucoma, get damage even with normal pressure.
• 0:39
  SPEAKER_00: These facts tell us that simply draining fluid is not enough.
• 0:42
  SPEAKER_00: Glaucoma is fundamentally a neurodegenerative disease.
• 0:46
  SPEAKER_00: Nerves are dying.
• 0:48
  SPEAKER_00: Scientists are now exploring whether new drugs can modify the disease itself rather than just treating pressure, by protecting the nerves and improving the eye's blood supply.
• 0:57
  SPEAKER_00: In this article, we'll explain what disease modifying means in glaucoma and why it's exciting.
• 1:04
  SPEAKER_00: We'll look at the importance of ocular blood flow and the endothelin pathway, which can choke blood vessels, and how improving blood flow or cell health might save vision.
• 1:13
  SPEAKER_00: We'll also cover PR01, a new drug in development by Perfuse Therapeutics, now owned by Bayer, which targets endothelin.
• 1:23
  SPEAKER_00: We'll weigh the evidence, what's been shown so far in small trials, what's still uncertain, and discuss what the future might hold in three ten years.
• 1:32
  SPEAKER_00: The tone is hopeful but realistic.
• 1:34
  SPEAKER_00: Disease modifying therapies could change how we treat glaucoma, but they are not cures, at least not yet.
• 1:41
  SPEAKER_00: What disease modifying means in glaucoma?
• 1:45
  SPEAKER_00: A disease-modifying therapy is one that changes the course of the disease itself, instead of just relieving symptoms.
• 1:51
  SPEAKER_00: In glaucoma, that would mean a drug that actually slows or stops the nerve cell death in the eye, not just reduces pressure.
• 1:59
  SPEAKER_00: It's a bit like how some arthritis drugs do more than just mask pain by slowing joint damage.
• 2:04
  SPEAKER_00: For glaucoma, the idea is often called neuroprotection, protecting the retinal ganglion cells, RGCs, the neurons that carry vision signals from the eye to the brain.
• 2:15
  SPEAKER_00: A classic definition says neuroprotection is treating glaucoma by a mechanism independent of lowering IOP.
• 2:22
  SPEAKER_00: Right now, no therapy has been proven to do this in patients.
• 2:26
  SPEAKER_00: In large, decades-long studies, only pressure lowering showed a clear benefit.
• 2:31
  SPEAKER_00: In fact, a 2023 review in molecular aspects of medicine notes that current strategies only target intraocular pressure and do not directly target the neurodegenerative processes of glaucoma.
• 2:43
  SPEAKER_00: It adds that up to 40% of patients still progress to blindness in at least one eye despite strict pressure control.
• 2:51
  SPEAKER_00: So researchers say we urgently need therapies that go beyond pressure.
• 2:56
  SPEAKER_00: In plain terms, imagine the optic nerve as a plant that not only needs the right water pressure, but also good soil and light.
• 3:04
  SPEAKER_00: Pressure drops help water travel, good.
• 3:07
  SPEAKER_00: But if the root cells are sick or starved, the plant will still die.
• 3:11
  SPEAKER_00: Disease-modifying treatments aim to brighten the light or improve the soil, directly helping the cells survive and function.
• 3:18
  SPEAKER_00: Blood flow and endothelin, why they matter.
• 3:22
  SPEAKER_00: One big area of research is improving ocular blood flow.
• 3:26
  SPEAKER_00: The retina is one of the body's hungriest tissues for oxygen and nutrients.
• 3:30
  SPEAKER_00: It's like a high-performance engine needing constant fuel.
• 3:33
  SPEAKER_00: If blood flow to the retina or optic nerve is compromised, cells can suffer from ischemia, lack of oxygen.
• 3:40
  SPEAKER_00: Over time, even shortfalls in blood supply can kill retinal ganglion cells.
• 3:45
  SPEAKER_00: Many people with glaucoma have vascular issues.
• 3:48
  SPEAKER_00: For example, some have a condition called flammer syndrome, blood vessels that overreact, or low blood pressure at night, which can worsen eye blood flow.
• 3:57
  SPEAKER_00: In normal tension glaucoma, glaucoma at normal pressures, poor blood flow is thought to be a key culprit.
• 4:04
  SPEAKER_00: Scientific studies support this.
• 4:06
  SPEAKER_00: For example, an experiment showed that giving endothelin-1, a natural chemical, to animals reduced blood flow in the retina and optic nerve, causing ischemic damage.
• 4:17
  SPEAKER_00: The same molecule, endothelin-1, also raises pressure and promotes optic nerve injury.
• 4:23
  SPEAKER_00: Endothelin is perhaps the most potent vasoconstrictor in the human body.
• 4:27
  SPEAKER_00: Imagine it like a very strong clamping of blood vessels.
• 4:30
  SPEAKER_00: In glaucoma patients, blood levels of endothelin-1 tend to be higher than normal.
• 4:36
  SPEAKER_00: Researchers even found that blocking endothelin receptors in healthy animals had no effect on normal flow, but giving extra endothelin caused a big drop in blood flow.
• 4:46
  SPEAKER_00: In other words, endothelin ramps up only when things are already bad.
• 4:51
  SPEAKER_00: Why is this important?
• 4:52
  SPEAKER_00: If endothelin-1 is high in glaucoma, it could constrict the small vessels in the eye, depriving nerve cells of oxygen.
• 5:00
  SPEAKER_00: A 2011 review on endothelin in glaucoma put it neatly.
• 5:05
  SPEAKER_00: Increased endothelin can lead to pathological changes in the retina and optic nerve head, which is assumed to contribute to the degeneration of retinal ganglion cells.
• 5:15
  SPEAKER_00: In simpler terms, high endothelin is like turning down the road supply to the optic nerve while also turning up the pressure, double whammying the nerve.
• 5:24
  SPEAKER_00: Therefore, drugs that block endothelin, called endothelin receptor antagonists, could in theory keep vessels open and protect nerves.
• 5:33
  SPEAKER_00: Is there evidence OBF ocular blood flow matters in patients?
• 5:38
  SPEAKER_00: Measurements of blood flow in glaucoma eyes often show abnormalities, and the risk of glaucoma goes up if perfusion pressure, blood pressure minus IOP, is too low.
• 5:48
  SPEAKER_00: Clinically, some glaucoma patients benefit from treatments that improve ocular perfusion.
• 5:53
  SPEAKER_00: For example, some doctors manage blood pressure or use calcium channel blockers off-label.
• 5:58
  SPEAKER_00: But so far, there is no approved glaucoma drug whose main action is boosting blood flow.
• 6:04
  SPEAKER_00: That's changing in research.
• 6:06
  SPEAKER_00: The idea is that if we can safely open up the eye's blood vessels or correct vascular dysregulation, we might protect the optic nerve from ischemic damage.
• 6:15
  SPEAKER_00: Mitochondria and retinal cell survival.
• 6:18
  SPEAKER_00: Another cutting-edge concept is mitochondrial protection.
• 6:21
  SPEAKER_00: Mitochondria are the power plants of cells, and retinal ganglion cells have extremely high energy demands.
• 6:28
  SPEAKER_00: They need a lot of ATP to maintain their long axons and signaling in the retina.
• 6:33
  SPEAKER_00: In glaucoma, several stresses, high pressure, free radicals, inflammation, can damage mitochondria, leading to energy failure and eventually cell death.
• 6:43
  SPEAKER_00: Some genetic forms of optic neuropathy, like Lieber's hereditary optic neuropathy, show that mitochondrial DNA problems cause RGC death.
• 6:52
  SPEAKER_00: In glaucoma, even without a genetic mutation, chronic stress may overload the mitochondria.
• 6:57
  SPEAKER_00: Researchers are testing ways to keep mitochondria healthy in glaucoma.
• 7:01
  SPEAKER_00: For instance, nicotinamide, vitamin B3, which boosts the mitochondrial energy molecule NAD plus, has shown promise.
• 7:09
  SPEAKER_00: In a small phase 2 trial, giving glaucoma patients a combination of nicotinamide and pyruvate, another metabolic fuel, led to a short-term improvement in visual function for many participants.
• 7:21
  SPEAKER_00: The treated patients had more visual field test points that got better, not just stopped worsening over a couple of months compared to placebo.
• 7:30
  SPEAKER_00: Although this was a very short-term result, and not yet evidence that visual loss is permanently slowed, it suggests that helping RGCs with extra fuel can improve how well they work.
• 7:41
  SPEAKER_00: There are other mitochondrial and cell targeting strategies under study.
• 7:46
  SPEAKER_00: Some are antioxidants to mop up free radicals, and others are drugs that block programs of cell death.
• 7:52
  SPEAKER_00: For example, experimental treatments that precondition cells using mild stress like low oxygen can activate built-in survival genes.
• 8:01
  SPEAKER_00: This stress response can make RGCs temporarily more resilient.
• 8:05
  SPEAKER_00: Another approach is using neurotrophic factors like brain-derived neurotrophic factor or BDNF, or growth factors to encourage cell survival.
• 8:14
  SPEAKER_00: In fact, an eyedrop-containing nerve growth factor, RHNGF, is now in early trials for glaucoma, aiming to block the signal that tells RGCs to die.
• 8:25
  SPEAKER_00: However, it's important to note that most of these strategies are experimental.
• 8:30
  SPEAKER_00: For instance, memantine, an Alzheimer's drug thought to protect nerve cells by blocking glutamate toxicity, underwent large clinical trials but did not significantly slow glaucoma compared to placebo.
• 8:41
  SPEAKER_00: So, while metabolic and protective approaches are very promising in concept, proof of lasting benefit in patients is still pending.
• 8:49
  SPEAKER_00: PIR-001 and other disease-modifying approaches.
• 8:53
  SPEAKER_00: A big hope in the field right now is a drug called PIR-001 from Perfuse Therapeutics, soon to be Bayer, an intravitrial inside-the-eye implant of an endothelin receptor antagonist.
• 9:05
  SPEAKER_00: This is exactly the strategy of blocking endothelin discussed above.
• 9:09
  SPEAKER_00: PER-001 slowly releases a small molecule that blocks endothelin receptors in the eye every six months or so.
• 9:17
  SPEAKER_00: The idea is to keep eye blood vessels open, reduce inflammation, and protect retinal cells, in addition to helping lower pressure through better outflow.
• 9:26
  SPEAKER_00: What do we know about PER01 so far?
• 9:29
  SPEAKER_00: Perfuse and Bayer have released encouraging early results.
• 9:33
  SPEAKER_00: In a phase one-half A study presented in 2025, a single PER-001 injection improved visual function and retinal structure compared to control over 24 weeks.
• 9:45
  SPEAKER_00: In plain terms, patients who got PR01 not only saw better on tests, but their optic nerve scans, like OCT, looked healthier.
• 9:54
  SPEAKER_00: Importantly, they also measured that ocular blood flow increased in treated eyes, confirming the drug was hitting its target.
• 10:01
  SPEAKER_00: In a later phase 2 trial, the companies report that some glaucoma patients actually gained vision back over six months, what they call reversed progressive vision loss, while controls continued to worsen.
• 10:14
  SPEAKER_00: As a reference, nearly all existing glaucoma trials simply slow vision loss, seeing any improvement is unusual.
• 10:22
  SPEAKER_00: Most of these PR-001 results are reported by the company in press releases, not in a peer-reviewed journal yet.
• 10:30
  SPEAKER_00: Still, they have attracted major attention.
• 10:32
  SPEAKER_00: Bayer alone announced plans to acquire Perfuse in 2026, noting PR-01's potential as one of the first disease-modifying treatments for both glaucoma and diabetic retinopathy.
• 10:45
  SPEAKER_00: Bayer's press release specifically highlights that PR-001 is being studied for its ability to improve the visual field for glaucoma patients and to reduce ischemia in diabetic eyes.
• 10:57
  SPEAKER_00: These phrases mean the drug is not just lowering pressure, but aiming to improve nerve function and blood flow.
• 11:04
  SPEAKER_00: However, caution is warranted.
• 11:06
  SPEAKER_00: These results so far come from small trials, tens of patients, and company press statements.
• 11:12
  SPEAKER_00: We do not yet have independent published data to review, and large studies can sometimes disappoint earlier excitement.
• 11:19
  SPEAKER_00: It's also worth noting that Pair 01 is delivered as an eye injection implant, a more invasive route than simple eye drops.
• 11:27
  SPEAKER_00: Patients may need to weigh the benefits against the burdens, though an injection every six months is fairly convenient compared to daily drops.
• 11:35
  SPEAKER_00: Other disease-modifying ideas are still at an earlier stage.
• 11:39
  SPEAKER_00: For example, eye drops or devices delivering neurotrophic factors like NGF are in early trials, and lifestyle strategies like exercise or supplements are being explored.
• 11:51
  SPEAKER_00: No other specific drug for advanced neuroprotection in glaucoma has shown conclusive success in humans yet.
• 11:58
  SPEAKER_00: Evidence, strong versus speculative.
• 12:01
  SPEAKER_00: What evidence do we have?
• 12:02
  SPEAKER_00: Strong evidence exists that lowering IOP helps most patients.
• 12:06
  SPEAKER_00: This is supported by decades of clinical trials.
• 12:09
  SPEAKER_00: Beyond that, evidence is still emerging.
• 12:11
  SPEAKER_00: The perfuse-Bayer data on PR01 are intriguing but preliminary.
• 12:16
  SPEAKER_00: Similarly, the nicotinamide trial showed short-term vision improvements.
• 12:20
  SPEAKER_00: But it's not known if that will translate into long-term protection.
• 12:25
  SPEAKER_00: Animal and laboratory studies give strong rationale for these approaches, e.g., it's well documented that ischemia and mitochondrial damage hurt RGCs, but animal models don't always predict human outcomes.
• 12:38
  SPEAKER_00: On the weak or speculative side, many treatments that looked good in the lab have failed in people.
• 12:44
  SPEAKER_00: Besides memantine, other antioxidants and supplements have had mixed results outside early studies.
• 12:50
  SPEAKER_00: Gene therapies or stem cell treatments are theoretically possible, but at this point they are more futuristic and not in any advanced glaucoma trials.
• 13:00
  SPEAKER_00: We also don't know the full risks of some neuroprotective agents in the eye.
• 13:04
  SPEAKER_00: In short, we are optimistic but not proven.
• 13:08
  SPEAKER_00: The therapies could slow glaucoma by protecting nerves, but that remains to be firmly established in clinical studies.
• 13:15
  SPEAKER_00: Looking ahead, three ten years, what might realistically reach patients in the next decade?
• 13:20
  SPEAKER_00: The short answer is hopefully something, but it will take time.
• 13:25
  SPEAKER_00: If Per01's mid-stage trials, phase 2B3, are successful, an FDA or EMA approval could be possible by the early 2030s.
• 13:34
  SPEAKER_00: That's roughly 7 to 10 years away.
• 13:36
  SPEAKER_00: In the nearer term, 3 to 5 years, we'll see more results from ongoing trials.
• 13:41
  SPEAKER_00: For instance, Perfuse planned a pivotal trial in late 2025, its outcomes in two, three years will be key.
• 13:48
  SPEAKER_00: Other companies and academic groups are likely testing the related endothelin blockers and neuroprotective drops.
• 13:55
  SPEAKER_00: Some changes don't require new FDA approvals.
• 13:59
  SPEAKER_00: Doctors might start recommending vitamins or supplements like nicotinamide off-label if larger studies confirm benefits, since it's relatively low risk.
• 14:08
  SPEAKER_00: There might also be new uses of existing drugs, for example, calcium channel blockers for vascular support, guided by research.
• 14:16
  SPEAKER_00: Importantly, ophthalmologists and patients should stay informed.
• 14:20
  SPEAKER_00: About 20 years ago, no one expected the first selective rho kinase inhibitor, nitarsudil, and nodonating prostaglandin, Letanoprostine bunod, would come along.
• 14:31
  SPEAKER_00: It's possible that even treatments designed for other eye diseases, like implants for retina ischemia in diabetic patients, could be tested in glaucoma too.
• 14:41
  SPEAKER_00: That said, it's realistic to say we're not about to cure glaucoma in the next few years.
• 14:46
  SPEAKER_00: Even if disease-modifying drugs do arrive, they will likely be added on top of the standard IOP lowering treatments, not replacing them entirely.
• 14:55
  SPEAKER_00: In the best case scenario, a patient might keep taking pressure-lowering drops and also get an injection or eye drop that helps protect their optic nerve.
• 15:04
  SPEAKER_00: Over 10 years, we may see gradual improvements, some patients maintaining vision longer, fewer advancing to blindness.
• 15:12
  SPEAKER_00: But we must also be prepared for setbacks.
• 15:15
  SPEAKER_00: Clinical research is full of surprises, both good and bad.
• 15:19
  SPEAKER_00: If a large trial fails, as happened with Mementine, that is valuable information too, guiding researchers to other targets.
• 15:27
  SPEAKER_00: Conclusion.
• 15:28
  SPEAKER_00: The search for disease-modifying glaucoma treatments is one of the most exciting areas in eye research today.
• 15:34
  SPEAKER_00: The basic idea is clear.
• 15:36
  SPEAKER_00: Pressure lowering helps many patients, but not all.
• 15:39
  SPEAKER_00: Improving blood flow, blocking harmful molecules like endothelin, and directly strengthening nerve cells could in principle protect vision further.
• 15:48
  SPEAKER_00: New drugs like PER001 are putting these ideas to the test.
• 15:52
  SPEAKER_00: Early signs are encouraging.
• 15:54
  SPEAKER_00: For example, one trial reported improved optic nerve blood flow and vision with an endothelin blocker, but we have to remember the early stage of this work.
• 16:04
  SPEAKER_00: For now, the best approach remains diligent eye pressure control and regular checkups, as proven by long-term studies.
• 16:11
  SPEAKER_00: Patients should discuss with their doctors about lifestyle factors like blood pressure, exercise, nutrition that support eye health.
• 16:20
  SPEAKER_00: Over the next five to ten years, we may realistically see the first drug approved to slow glaucoma by protecting nerves, a milestone, though still far from a cure.
• 16:30
  SPEAKER_00: Until then, it's wise to be hopeful but cautious.
• 16:33
  SPEAKER_00: Each new research finding brings us a step closer, but no magic bullet has emerged yet.
• 16:39
  SPEAKER_00: Science is making progress.
• 16:41
  SPEAKER_00: One day, these strategies might transform glaucoma care, but it will be a process.
• 16:46
  SPEAKER_00: Patients can look forward to more tools while still relying on the treatments that are proven today.
• 16:52
  SPEAKER_00: Summary, lowering eye pressure remains the mainstay for glaucoma, but it doesn't halt disease for everyone.
• 16:59
  SPEAKER_00: Researchers are pursuing disease-modifying therapies, aiming to directly protect retinal nerves by improving blood flow, blocking vasoconstrictors like endothilin, and boosting cellular energy.
• 17:11
  SPEAKER_00: The drug PR001, an endothelin blocker implant, is a leading example.
• 17:17
  SPEAKER_00: Early results suggest it can increase optic nerve blood flow and even improve vision in some patients.
• 17:22
  SPEAKER_00: Other ideas, vitamins, neurotrophic factors, etc., are in smaller trials.
• 17:27
  SPEAKER_00: However, all such evidence is preliminary.
• 17:30
  SPEAKER_00: We need larger clinical trials to prove that these approaches truly slow glaucoma.
• 17:35
  SPEAKER_00: In the next few years, watch for trials of Pier001 and similar drugs.
• 17:40
  SPEAKER_00: In 10 years, we might see the first approved neuroprotective glaucoma treatment.
• 17:45
  SPEAKER_00: Until then, patients should remain optimistic yet realistic.
• 17:49
  SPEAKER_00: These developments are exciting, but the cure for glaucoma has not yet arrived.
• 17:54
  SPEAKER_00: All links to sources are available in the text version of this article.
• 17:58
  SPEAKER_00: You can find the full article at VisualFieldtest.com.
• 18:02
  SPEAKER_00: Thanks for listening.
• 18:03
  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.