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What is Glaucoma?

Glaucoma is a group of eye diseases which results in damage to the optic nerve due to high intraocular pressure (IOP) of the eye from fluid build-up. Glaucoma is the second leading cause of vision loss.

According to Weinreb et al.’s, 2014 article “The pathophysiology and treatment of glaucoma: a review”, inadequate or obstructed drainage of the aqueous humor through the trabecular mesh increases the fluid pressure within the anterior chamber, subsequently propagating into the posterior chamber of the eye. The increased intraocular pressure exacts a toll on the basal membrane of the retina, thinning the mesh-like tissue in this region and damaging the head of the optic nerve. According to Quigley and Boman’s 2006 publication “The number of people with glaucoma worldwide in 2010 and 2020”, glaucoma is currently the second leading cause of blindness world-wide; it is estimated to affect a population close to 80 million by 2020.

Current glaucoma treatments work by lowering intraocular pressure either by inhibiting carbonic anhydrase in the eye, by reducing the production of aqueous humor by the ciliary epithelial cells, or by increasing fluid drainage through the trabecular meshwork. There is considerable room for improvement of existing drugs in terms of efficacy, safety, delivery, and the development of tolerance over time. As most of therapies are formulated as eye drops, studies have shown that only less than 5% of the dose formulation penetrates the cornea after eye drop administration; meaning that 95% of the administered drug never reaches its target. Thus, there is much room for improvement on the drug-delivery as a means of increasing clinical efficacy.

Learn more about glaucoma at the American Academy of Ophthalmology.

What causes Glaucoma?

Glaucoma is a group of eye diseases, which results in damage to the optic nerve and vision loss, according to the publication “Facts about Glaucoma” from the United States National Eye Institute. The most common type is open-angle glaucoma, or OAG, with less common types including closed-angle glaucoma, or CAG, and normal-tension glaucoma.

The mechanism of OAG is believed to be due to resistance to outflow of aqueous humor through the trabecular meshwork while in CAG may be caused by drainage channel blockage near the iris. Diagnosis is typically made by a dilated eye examination.

OAG develops slowly over time and there is no pain. If left untreated, however, side vision may begin to decrease followed by central vision. According to Mantravadi & Vadhar’s 2015 article titled “Glaucoma” in the “Primary Care” publication, CAG can develop gradually or suddenly with presentation involving severe eye pain, blurred vision, mid-dilated pupil, redness of the eye and nausea. Vision loss from glaucoma, once it has occurred, is permanent.

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Risk factors for Glaucoma

While glaucoma can affect anyone, certain people are at higher risk. According to “Facts about Glaucoma” from the United States National Eye Institute, increased risk factors for glaucoma include individuals with diabetes, hypertension, previous eye injury or a family history of the condition. Individuals at a higher risk also include African American age 40 and older and anyone 60 years of age and older (especially Hispanics/Latinos).

High eye pressure (those with a value of greater than 21 mmHg or 2.8 kPa) is often associated with a greater risk of glaucoma. However, some people may have high eye pressure for years and never develop optical nerve damage. Conversely, as reported Xue-Song Mi et al., in a 2014 publication “The current research status of normal tension glaucoma”, optic nerve damage may also occur with normal pressure, known as normal-tension glaucoma.

Glaucoma affects about 3.5% of global population, aged 40-80

According the the American Academy of Ophthalmology, glaucoma affects about 3.5% of the global population of those aged 40-80 years. It’s estimated that 76 million people are affected by glaucoma, of which 85% is open angle glaucoma (OAG). About 52.7 million people worldwide are affected by OAG of which 3.5 million are in the North America. By 2040, the glaucoma prevalence is projected to increase to 112 million worldwide and 4.7 million North America. It occurs more commonly among older people. Men are more likely to have open angle glaucoma than women. Glaucoma is the second-leading cause of blindness globally.

Current Glaucoma Treatments

Current treatments for glaucoma include medication, laser treatment and surgery. According to Mantravadi & Vadhar’s 2015 article titled “Glaucoma” in the “Primary Care” publication, the goals of glaucoma management are to avoid glaucomatous damage and nerve damage, and preserve visual field and total quality of life for patients, with minimal side effects. This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although intraocular pressure is only one of the major risk factors for glaucoma, lowering it via various pharmaceuticals and/or surgical techniques is currently the mainstay of glaucoma treatment.

If treated early, it is possible to slow or stop the progression of disease with medication, laser treatment, or surgery. The goal of these treatments is to decrease eye pressure. Currently, a number of different classes of glaucoma medication are available. Laser treatments may be effective in both OAG and CAG. A number of types of glaucoma surgeries may be used in people who do not respond sufficiently to other measures. Treatment of CAG is a medical emergency.

Current prescription eyedrop medications include:

  • Prostaglandins such as latanoprost, bimatoprost and travoprost to increase the outflow of fluid from the eye and reduce ocular pressure. These can sting the eyes, darken the iris and eyelashes, and blur vision.
  • Beta blockers such as timolol and betaxolol reduce ocular pressure by reducing the production of fluid in the eye. Possible side effects include wheezing or difficulty breathing, slowed heart rate, lower blood pressure, impotence and fatigue.
  • Alpha-adrenergic agonists such as apraclonidine and brimonidine, both reduce the production of aqueous humor and increase the outflow of fluid from the eye. Side effects may include dry mouth, red eyes or eyelids, fatigue, low or high blood pressure, blurred vision and light sensitivity.
  • Carbonic anhydrase inhibitors such as dorzolamide and brinzolamide also reduce the production of fluid in the eye, but they are associated with blurred vision, bitter metallic taste in the mouth, dry eyes, red/irritated eyes, headache, and upset stomach.

Often patients need to take multiple eye drops throughout the day. Given the side effect profiles, many patients don’t take their medications properly or at all.

Surgery and laser therapies are intended to physically improve the drainage of fluid from the eyes, lowering pressure. Patients with OAG can have clogged channels in the trabecular network opened with laser therapy, filtering surgery (trabeculectomy) or electrocautery. In other cases, small drainage tubes may be implanted in the eye. Possible complications include pain, redness, infection, inflammation, bleeding, abnormally high or low eye pressure and loss of vision. Some types of eye surgery may speed the development of cataracts. Additional procedures may be needed if eye pressure continues to increase.

 

Cannabinoids a promising treatment option for glaucoma

The use of cannabis to treat glaucoma has extensive anecdotal evidence and supporting clinical data. It has been definitively demonstrated in articles that smoking cannabis lowers intraocular pressure (IOP) in both normal individuals and in those with glaucoma.

Learn more about the history of cannabis and glaucoma.

InMed is Developing a Cannabinoid Formulation for Glaucoma

INM-088 is a topical, single cannabinoid formulation under development for the treatment of glaucoma. The active pharmaceutical ingredient (API) in INM-088 is cannabinol, also known as CBN, a rare cannabinoid showing promise in its potential to provide neuroprotection and reduce intraocular pressure of the eye.

InMed is developing INM-088 to provide a dual mechanism of action:

  • Reduce the intraocular pressure (IOP) in the affected eyes
  • Provide neuroprotection for the retinal ganglion cells (RGCs) and other optic nerve tissues in the affected eyes.