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What Is Glaucoma?

What Is Glaucoma?

Glaucoma is a group of progressive, blinding, optic neuropathies characterized by irreversible loss of optic nerve axons and retinal ganglion cells. High intraocular pressure (IOP) has been conclusively shown to increase the risk for both development and progression of glaucomatous neurodegeneration. About 75% of Americans with glaucoma have open angle glaucoma (OAG), where the pathophysiology of increased IOP involves reduced outflow facility.

Prevalence and existing treatment

Glaucoma is the leading cause of irreversible blindness worldwide.

Open angle glaucoma is a leading cause of irreversible blindness in the US and the world affecting about 2.7 million American and 57.5 million patients worldwide and costing the US economy $2.86 billion annually. 

The prevalence and severity of glaucoma are even higher in African Americans and Hispanics. About 300,000 new patients are diagnosed with glaucoma in the US every year. The cost to the US economy for medical care, disability, and low vision rehabilitation is almost $3 billion annually. Furthermore, the prevalence of glaucoma is expected to increase dramatically as the population ages. Annual medical costs are projected to top $17 billion by 2050. OAG is dependent on IOP, with high IOP being a causal risk factor for the disease. Approximately 7–8% of individuals above age 40 have elevated IOP. 

Since IOP is the only modifiable risk factor for OAG, IOP lowering is the only effective way of preventing visual disability from OAG. In OAG, malfunction or pathology of the outflow tissues leads to increased outflow resistance and IOP elevation. Most eyedrop medications used to lower IOP act by either reducing the production of aqueous humor (β-adrenergic antagonists, α2-adrenergic agonists, carbonic anhydrase inhibitors) or increasing uveoscleral outflow (which accounts for a small portion of the total outflow of aqueous humor in humans). 

Since uveoscleral outflow and aqueous humor production (flow) are not different between glaucoma patients and healthy controls, only Rho-kinase inhibitors and parasympathomimetic agents primarily act at the site of pathology, namely the TM. Both of these medication classes have significant side effects. Laser therapy (trabeculoplasty) can be used to lower IOP but its effect is modest and does not last very long. For patients with uncontrolled OAG, incisional surgery may be an option but is highly invasive, can cause significant complications, and typically fails over time.

Healthy Eyes

Peripheral vision loss due to Glaucoma

Unmet medical need

There is a need for new disease modifying long-lasting therapies that can counteract or correct the pathology of the outflow tissues and normalize IOP while relieving the patient burden and responsibility of frequent drug administration. IOP-lowering eye-drops require chronic administration, often of multiple drugs multiple times daily. These treatments also do not address the underlying disease pathology in the outflow tissues. Poor patient compliance: it is estimated that 30 to 50% of the patients are not compliant with the treatment
  • ~25% of patients will require surgery at some point
  • ~ 120,000 Americans are blind from glaucoma
  • 4% of newly diagnosed patients will go bilaterally blind from glaucoma despite many treatment options (including eyedrops, lasers and incisional surgery)
  • Slow vision loss, even before blindness, leads to patients losing their independence, the ability to drive and turning to family members for help with routine tasks. Individuals with glaucoma have a three times greater risk of falls and a six times greater risk for auto accidents
A number of pharmaceutical companies are currently pursuing extended-release small molecular formulations of existing agents but these have not achieved much success to date, as they require invasive administration and their effect last only a few months.

Our disease modifying gene therapy targets a single administration for long-term lowering of IOP and significantly reducing the risk of blindness
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