Genetic basis of glaucoma

Northwestern Medicine scientists and international collaborators discovered mutations that cause improper drainage and a buildup of ocular pressure leading to one form of congenital glaucoma, and identified a path towards future treatments for the disease. Susan Quaggin, MD, chief of Nephrology and Hypertension in the Department of Medicine and director of the Feinberg Cardiovascular Research Institute, was senior author on the studies.

Glaucoma is a leading cause of blindness around the globe, and elevated intraocular pressure (IOP) is an important risk factor for the disease. Developmental defects in the anterior chamber of the eye, including a drainage vessel called Schlemm's canal, can lead to a particularly severe form of glaucoma in children known as primary congenital glaucoma (PCG).

Previous studies from Quaggin and her collaborators have shown loss-of-function mutations in the angiopoietin (ANGPT) receptor TIE2/TEK in families with PCG, and that ANGPT/TIE2 pathway activity is critical for Schlemm's canal development.

 In the JCI study, Quaggin and her colleagues used mice models to explore the importance of individual components of the ANGPT/TEK pathway, finding mice without the growth factor ANGPT1 had severely deformed and small Schelmm's canals. In addition, loss of TIE2/TEK, the angiopoietin receptor, had a similar effect.

Both ANGPT1 and TIE2/TEK are essential to form the drainage system of the eye to regulate intraocular pressure and prevent Glaucoma. Researchers found two human subjects with loss-of-function mutations in ANGPT1 within an international group of PCG patients, further supporting a causative role for ANGPT1 in the disease.

In the PNAS study, Quaggin and her colleagues searched for ways to influence the molecular pathway they'd identified. In particular, inhibition of TIE2/TEK has been linked to vessel leakage and inflammation, so finding a way to activate TIE2/TEK was a priority. Using mouse models, investigators found inhibition of a protein called VEPTP allowed ANGPT2 to be used as a TIE2/TEK activator, providing a blueprint for a pharmacological solution.
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Rhopressa for treating glaucoma

Rhopressa (netarsudil ophthalmic solution) 0.02%, is a novel once-daily eye drop for the lowering of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Rhopressa is believed to reduce IOP by increasing the outflow of aqueous humor (the fluid inside the eye) through the trabecular meshwork, the main fluid drain of the eye.

Rhopressa (netarsudil ophthalmic solution) is a Rho kinase inhibitor for the treatment of open-angle glaucoma or ocular hypertension. Use one drop in the affected eye(s) once daily in the evening. If a dose is missed, treatment should continue with the next dose in the evening. Avoid allowing the tip of the dropper to contact the eye, surrounding structures, fingers, or any other surface in order to minimize contamination of the solution.

 Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Rhopressa contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of Rhopressa and may be reinserted 15 minutes following its administration.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications. The most common side effect is eye redness. Other common side effects include corneal verticillata, pain at the instillation site, and conjunctival hemorrhage.
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Drinking tea reduces the risk of glaucoma

A daily cup of tea slashes the risk of developing a serious eye condition. People who drink a cup of hot tea at least once a day are 74 per cent less likely to be diagnosed with glaucoma - a severe eye problem. But coffee, iced tea and soft drinks don't seem to make any difference, the researchers found.

The University of California team found a significant link between tea and glaucoma. Glaucoma, one of the leading causes of blindness, causes fluid pressure to build up inside the eye, damaging the optic nerve.

The scientists believe the antioxidants and natural anti-inflammatory chemicals in tea may play a role in protecting against this process. Glaucoma becomes more common with age, and is a significant cause of blindness.

Tea is a healthy drink, rich in antioxidant polyphenols such as tea catechins and other flavonoids. However, in this research it wasn't the type of tea or its strength that appeared protective, rather the temperature at which it was drunk.
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Vyzulta for treating glaucoma

Vyzulta, a once daily monotherapy with a dual mechanism of action, works by metabolizing into two moieties, latanoprost acid, which primarily works within the uveoscleral pathway to increase aqueous humor outflow, and butanediol mononitrate, which releases nitric oxide NO to increase outflow through the trabecular meshwork and Schlemm's canal.

The most common ocular adverse events include conjunctival hyperemia, eye irritation, eye pain and instillation site pain. Increased pigmentation of the iris and periorbital tissue and growth of eyelashes can occur. In glaucoma patients, damage to the trabecular meshwork, through which the majority of the aqueous humor passes, can lead to reduced drainage and as a result elevated intra ocular pressure IOP. Lowering IOP, even in patients with normal baseline levels, can delay, or even prevent damage to optic nerves, helping to reduce the risk of glaucomatous visual field loss.

Preclinical studies have shown that NO plays a role in controlling IOP in normal eyes by increasing aqueous humor outflow through the trabecular meshwork and Schlemm's canal. Studies have also demonstrated that patients with glaucoma have reduced levels of NO signaling in their eyes, providing a rationale for the therapeutic value of NO-releasing molecules for patients with open-angle glaucoma or ocular hypertension.

The safety and efficacy of Vyzulta has been well-established through multiple clinical studies, which have demonstrated positive results, including statistically significant differences in IOP lowering compared to timolol and latanoprost. Vyzulta provides a new treatment option that works to reduce IOP by increasing the outflow through both the trabecular meshwork and the uveoscleral pathways.

Increased pigmentation of the iris, periorbital tissue (eyelid), and eyelashes can occur. Iris pigmentation is likely to be permanent. Gradual changes to eyelashes, including increased length, increased thickness, and number of eyelashes, may occur. These changes are usually reversible upon treatment discontinuation.
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Facts about glaucoma

There are an estimated 64 million people worldwide with glaucoma, a group of eye conditions in which the main nerve to the eye - the optic nerve becomes damaged.

Optic nerve carries information about what is being seen from the eye to the brain - but when it becomes damaged, vision is lost.

According to the Glaucoma Research Foundation, it is now a leading cause of blindness. It's common in men and
women over the age of 40, and if left untreated it can lead to up to 40 per cent of sight being permanently damage.

There are often no early symptoms of glaucoma, but when it becomes more advanced, signs may include missing or patchy sight or even serious loss of vision.

However, if detected early, it can be managed and useful sight can be maintained for years to come.
Although ten per cent of people with glaucoma who receive proper treatment still experience loss of vision.

Regular check-ups with an optician every two years, or one to two years if you’re over 40 is recommended. A
recent study found it may be possible to predict glaucoma in this way up to ten years in advance. Glaucoma is treated
with eye drops which must be used for a long period of time.