Glaucoma: The “Silent Thief of Sight”
Glaucoma is known as the “silent thief of sight.” According to JAMA Ophthalmology, nearly four million people had glaucoma and nearly 1.5 million of them were impacted by the loss of vision due to glaucoma.
Dr. Abbot Clark, FARVO is a regents professor in pharmacology and neuroscience at UNT Health Fort Worth in the College of Biomedical and Translational Sciences and NTERI faculty. His research focuses on glaucoma, gives some insight into this condition and the breakthroughs in how we diagnose and treat glaucoma.
What exactly is glaucoma?
Glaucoma is the leading cause of irreversible vision loss and blindness in the world, affecting approximately 80 million individuals. There are several different types of glaucoma, but all are characterized by specific damage to the optic nerve – which carries the visual signals to the brain – at the optic nerve head and specific changes to the visual field. Most forms of glaucoma are associated with a buildup of pressure within the eye, called intraocular pressure or IOP, that initiates damage to the back of the eye and to the optic nerve. Currently, glaucoma is treated by eye drops or surgery to lower IOP and prevent or delay further damage.
How common is glaucoma, and who is most at risk of developing it?
Glaucoma is a common neurodegenerative disease affecting 1-4% of the population over the age of 40. Certain populations such as those of African descent and Hispanics have a higher chance of developing glaucoma compared to those of European descent. Although there are congenital and juvenile forms of glaucoma, most glaucoma is age dependent with increased risk after the age of 40. Family history also is an important risk factor.
What happens inside the eye when someone develops glaucoma?
Glaucoma damages several structures within the eye. An important risk and causal factor for the development and progression of glaucoma is increased pressure within the eye. There is continuous turnover of aqueous humor in the front of the eye that is regulated by a tissue known as the trabecular meshwork, which becomes progressively damaged in glaucoma leading to elevated IOP. Increased pressure within the eye damages the optic nerve head where specific retinal nerves begin to form the optic nerve. This initial insult at the optic nerve head leads to the loss of retinal cells and their axons, which are responsible for carrying the visual signals to the brain. In addition to progressive damage to the TM, optic nerve head, and optic nerve, the regions of the brain responsible for vision also are damaged in glaucoma.
Could you explain, in simple terms, what your current research on glaucoma is focused on?
All current glaucoma therapies (eye drops and surgeries) target lowering IOP, which in many cases slows the progression of glaucoma. However, current therapies do not address the underlying causes of glaucoma (for example, glaucomatous damage to the TM). Research in my laboratory is focused on discovering the underlying molecular causes of glaucoma so that we can develop new and better disease modifying therapies that prevent and/or reverse glaucomatous damage to the eye.
What inspired you to study glaucoma in particular?
When I was a junior faculty member at UT Southwestern Medical Center, I was invited to Alcon Laboratories to give a lecture on the mechanisms of action of a class of anti-inflammatory compounds. At the end of my lecture, the VP of Research at Alcon asked me to join Alcon as a senior scientist. I thought that I might try industry for several years but ended up staying at Alcon for 23 years becoming VP of Discovery Research and Head of Glaucoma Research prior to returning to academia at UNT Health 17 years ago. Within my first year at Alcon, I became fascinated with glaucoma and thought that I could contribute to discovering the cause(s) of glaucoma and develop better ways of treating glaucoma. This has been the major focus of my research for decades.
How might your research change how we diagnose or treat glaucoma in the future?
I was involved in the discovery of the first glaucoma gene (a gene called MYOC) in collaboration with close colleagues at the University of Iowa. We discovered the molecular mechanisms responsible for MYOC glaucoma and have developed a gene editing approach to treat patients that have MYOC glaucoma, which we hope to take to the clinic. My lab (that includes graduate students, postdoctoral fellows, and research associates) has discovered the molecular mechanisms responsible for glaucomatous damage to the TM and optic nerve head, and are developing new disease modifying therapies, including gene therapies, that we also hope to test in clinical trials. There is a strong genetic susceptibility to develop glaucoma, and we are working with a large consortium of glaucoma scientists and clinicians to develop a glaucoma risk calculator that will allow clinicians to more closely follow individuals that have the genetic make-up placing them at higher risk for developing glaucoma.
Is there a recent breakthrough or finding from your lab that you’re especially excited about?
My graduate student, Sam Yacoub – who will be defending his dissertation at the end of this month – and I have worked closely with former NTERI investigator Gulab Zode to develop an inducible mouse model of glaucoma that mimics all aspects of human glaucoma. We have shown that we can cure glaucoma in this model using genome editing technology. Former graduate student Gaurang Patel and our lab cured glaucoma in a steroid-induced glaucoma mouse model using gene therapy. We hope to be able to take these discoveries into clinical trials.
What challenges do you face when studying glaucoma, and how do you address them?
Glaucoma is a multi-factorial group of diseases, and we are challenged to find common molecular pathways that are damaging the eye in glaucoma. Although we can cure glaucoma in mouse models of glaucoma, a major challenge is to show that this therapeutic approach is relevant to human glaucoma. We are using cells and tissues cultured from control and human donor eyes to validate our new discoveries. We then need to test these new therapies in well designed, controlled and FDA-approved clinical trials.
What are some early warning signs people should look out for?
Glaucoma is known as the “silent thief of sight” because it generally is painless with slowly progressive loss of sight. Vision loss usually initially affects peripheral vision, which is hard to detect, and often manifests with problems with night vision, especially when driving at night. Unfortunately, there is considerable and irreversible loss of neurons responsible for carrying the visual signals to the brain by the time glaucoma is diagnosed. It is essential to get annual vision exams that include dilation of the pupil to fully visualize the optic nerve head, especially for individuals at greater risk for developing glaucoma, such as a family history of glaucoma, if you are of African or Hispanic descent, have high myopia, and/or are over the age of 45.
What’s the biggest misconception people have about glaucoma?
In general, most people do not understand glaucoma and often confuse this disease with other ocular abnormalities (for example, cataracts). More than half of those with glaucoma are unaware that they have glaucoma, so annual visual examinations are required. Current glaucoma therapies usually slow disease progression, allowing most individuals with glaucoma to have functional vision throughout their lifetimes. Only about 10% of glaucoma patients become blind in their lifetimes.
For more information on NTERI, please visit our website to learn more about eye health and research.
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