Glaucoma and Neurodegeneration: Recent Developments

Glaucoma is one of the leading causes of blindness in the United States. Because of this, scientists gave sufficient attention to developing advanced medical treatments for this disease. As they probe deeper into the cause of this disease, it becomes clearer that certain genes play a significant role in acquiring and treating this chronic condition. In trying to understand the progress made, we will examine the genetics of glaucoma and what the latest research says about it. One topic we will especially delve into is the underlying connections geneticists are seeing in the relationship between glaucoma and neurodegenerative diseases.

Glaucoma and the Recent Numbers

The optic nerve serves as the connection between the cells in your eyes, called the ganglion cells, and your nervous system. This connection interprets the reflection of light from our surroundings into recognizable images. Glaucoma is a disease that damages these optic nerves. Doctors attribute this damage to a yet unexplained build-up of pressure in the eye or intraocular pressure (IOP). Due to this damage, it can lead to loss of peripheral vision and ultimately, blindness.

The most prevalent kind of glaucoma exists in the form of primary open-angle glaucoma (POAG). Currently, this specific disease is one of the leading causes of irreversible blindness in the world. In a 2021 cohort study of the disease, scientists analyzed data from 2000 to 2020. The study collated 50 publications with a total of 198,259 subjects or patients. The following are the results:

  • Throughout the whole population of the world from 2000 to 2020, POAG has had an overall prevalence of 2.4%.
  • The prevalence of the disease increases with age.
  • Men are more vulnerable to the disease at a relative risk of 1.28 as compared to women.
  • Among all the continents, the highest prevalence of the disease occurs in Africa at 4.0%. 
  • As of 2020, an estimated 68.56 million people had the disease.

In comparison to the prevalence of POAG, breast cancer, the most common cancer in the world, had 2.26 million cases in women as of 2020. The second most common, lung cancer, had 2.2 million cases in both men and women.

From the figures above, we can see an urgent need for a cure for glaucoma. However, there is currently no cure for it. Although, if detected early, there are means to treat it and prevent it from getting worse.

Before scientists could begin to devise a treatment, they still had to pinpoint what exactly causes the increased IOP that causes nerve damage. Through their continuous research, they are now looking into the genetics of glaucoma and its neurodegenerative implications.

Glaucoma and Neurodegeneration

Since glaucoma is a lifelong chronic disease with no cure yet, it is one of those conditions that brings a physical and mental burden on the patient. Intuitively, one can say that glaucoma results in psychological conditions such as anxiety and depression. However, scientists suspect that the other way around may also be true. This means that some neurodegenerative conditions may affect glaucoma. 

Researchers thoroughly examined these psychological conditions and its relationship with glaucoma. In 2021, a case-control study on this relationship looked into 251 patients with open-angle glaucoma. The following are the results of the study:

  • Optic disk hemorrhage, peak IOP, and retinal nerve fiber layer (RNFL) thickness loss rate significantly correlate with increased anxiety. 
  • Optic disk hemorrhage and RNFL thinning rate significantly correlate with anxiety.
  • RNFL thickness loss rate and Beck Anxiety Inventory score had a significant positive correlation.
  • RNFL loss and IOP fluctuation had a significant positive correlation.
  • Visual field means deviation and heart rate variability significantly correlated with increased depression.

Although this study showed no evidence of causality, the researchers suggest that anxiety may have a role in the progression of glaucoma. They suggest this because the first point above shows increased anxiety being associated with known glaucoma indicators such as disk hemorrhage, IOP profile, and RNFL thickness loss.  Additionally, recent studies have also noticed the increase in glaucoma progression in patients with anxiety or depression.

Glaucoma-Alzheimer’s Relationship

To further explore the relationship between glaucoma and neurodegenerative conditions, we turn to one of the recently increasing evidence of the connection between glaucoma and Alzheimer’s disease (AD). Researchers are now aware of the common neurodegenerative pathways between glaucoma and other brain disorders such as chronic traumatic encephalopathy and frontotemporal dementia. 

The Apolipoprotein E (APOE), the gene that causes AD, seems to be the primary suspect for its connection with glaucoma. The APOE gene is responsible for regulating the molecules called Galectin-3. These molecules can induce the death of retinal ganglion cells, which then cause glaucoma. According to recent research that just came out on the 16th of August, the APOE4 gene variant can decrease the risk of glaucoma by inhibiting the production of Galectin-3. However, this in turn can increase the risk for AD since the APOE gene itself is the risk gene for the disorder. 

While the discovery may seem impractical, it shows researchers that there are new ways to treat glaucoma. Knowing this pathway can provide new techniques and options to combat this eye disease.

Glaucoma Treatment Trends

As of today, the conventional ways to treat glaucoma from getting worse are medicine, laser treatment, and surgery. In medicine treatment, one of the challenges that doctors face is penetrating the ocular barriers to administer the ophthalmic drugs. As of June 2022, these are the drug carriers with potential for medicine treatment of glaucoma:

  • Inorganic-based: uses inorganic nanoparticles such as carbon or silver 
  • Polymeric-based: uses biological polymers such as cellulose 
  • Hydrogel-based: uses hydrogels in intraocular lens and vitreous substitutes 
  • Contact lens-based: uses contact lens loaded with ophthalmic drugs

All these treatments work to target the tissues and attempt to help recover the damaged optic nerves. In turn, this should help lower the IOP.

Although there may not be a cure yet, doctors place early detection of the disease to prevent worsening of your eyesight. If you experience some intense eye pain, nausea, red eyes, or blurry vision, you should immediately contact your doctor.

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