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| ====== HISTORY ====== | ====== HISTORY ====== | ||
| - | The word "glaucoma" is derived from the Ancient Greek word glaukos which means blue, green, or gray. The term was first used by Hippocrates in Greece in 400 BC to describe a dimming of vision (Realini, 2011). For many years the condition of glaucoma was known, yet treatment was unavailable for thousands of years because there was not much of an understanding of its underlying cause (Realini, 2011). In fact, there was a misconception that glaucoma is caused by the opacification of the vitreous humour in the eye. It was not until 1622, that ophthalmologist Richard Bannister linked glaucoma to an increase in intraocular pressure (Realini, 2011). A clear understanding of the condition did not progress much further until the mathematician Charles Babbage and Hermann von Hemholtz created the first ophthalmoscope in 1851, which was an instrument used to view the interior of the eye. After this invention, Albrecht von Graefe, a German, began a series of clinical tests that solidified the anatomical characteristics associated with glaucoma (Realini, 2011). | + | The word "glaucoma" is derived from the Ancient Greek word glaukos which means blue, green, or gray. The term was first used by Hippocrates in Greece in 400 BC to describe a dimming of vision (Realini, 2011). For hundreds of years the condition of glaucoma was known, yet treatment was unavailable because there was not much of an understanding of its underlying cause (Realini, 2011). In fact, there was a misconception that glaucoma is caused by the opacification of the vitreous humour in the eye. It was not until 1622, that ophthalmologist Richard Bannister linked glaucoma to an increase in intraocular pressure (Realini, 2011). A clear understanding of the condition did not progress much further until the mathematician Charles Babbage and Hermann von Hemholtz created the first ophthalmoscope in 1851, which was an instrument used to view the interior of the eye. After this invention, Albrecht Von Graefe, a German physician, began a series of clinical tests that solidified the anatomical characteristics associated with glaucoma (Realini, 2011). |
| ====== EPIDEMIOLOGY ====== | ====== EPIDEMIOLOGY ====== | ||
| - | It is estimated that there are 60 million people with glaucoma and 8.4 million people who are blind due to glaucoma in 2012 (Cook & Foster, 2012). Specifically, it is estimated that 4.5 million people are blind due to open-angle glaucoma and 3.9 million are blind due to angle-closure glaucoma. In open-angle glaucoma, the angle in your eye where the iris meets the cornea is as wide and open as it should be, but the eye's drainage canals become clogged over time, causing an increase in internal eye pressure and subsequent damage to the optic nerve. With angle-closure glaucoma, the block takes place at the angle of the anterior chamber formed by its junction of the cornea with the iris, again leading to a sudden (acute) or slowly progressive (chronic) blockage of the normal circulation of fluid within the eye. By 2020, it is estimated that 80 million people will be affected by glaucoma, with 5.9 million and 5.4 million people blind due to open-angle and angle-closure glaucoma, respectively (Quigley & Broman, 2006). | + | It is estimated that there were 60 million people with glaucoma and 8.4 million people who are blind due to glaucoma in 2012 (Cook & Foster, 2012). Specifically, it is estimated that 4.5 million people are blind due to open-angle glaucoma and 3.9 million are blind due to angle-closure glaucoma. In open-angle glaucoma, the angle in your eye where the iris meets the cornea is as wide and open as it should be, but the eye's drainage canals become clogged over time, causing an increase in internal eye pressure and subsequent damage to the optic nerve. With angle-closure glaucoma, the block takes place at the angle of the anterior chamber formed by its junction of the cornea with the iris, again leading to a sudden (acute) or slowly progressive (chronic) blockage of the normal circulation of fluid within the eye. By 2020, it is estimated that 80 million people will be affected by glaucoma, with 5.9 million and 5.4 million people blind due to open-angle and angle-closure glaucoma, respectively (Quigley & Broman, 2006). |
| - | Prevalence of glaucoma also varies with racial group. Asians are the largest group affected, comprising 47% of the total affected, with all types of glaucoma, and 87% of primary angle-closure glaucoma (Cook & Foster, 2012). On the other hand, Africans have the highest prevalence of primary open-angle glaucoma. Prevalence of primary open-angle glaucoma is similar between white Europeans, Americans, and Australians. Additionally, women are more affected than men, making up 59% of all glaucoma (Cook & Foster, 2012). | + | Prevalence of glaucoma also varies among different racial group. Asians are the largest group affected, comprising 47% of the total affected, with all types of glaucoma, and 87% of primary angle-closure glaucoma (Cook & Foster, 2012). On the other hand, Africans have the highest prevalence of primary open-angle glaucoma. Prevalence of primary open-angle glaucoma is similar between white Europeans, Americans, and Australians. Additionally, women are more affected than men, making up 59% of all glaucoma (Cook & Foster, 2012). |
| There are also risk factors associated with primary open-angle glaucoma. African people have a prevalence up to 5 times higher than other ethnic groups of developing glaucoma (Cook & Foster, 2012). You risk of developing glaucoma exponentially increases with age. Particularly, Hispanics have a more pronounced increased risk of developing glaucoma with age compared to other ethnic groups (Cook & Foster, 2012). Additionally, having a thin cornea and/or a large optic disc diameter has shown to increase one's risk for glaucoma. Other factors associated with higher risk is low physical activity, having cardiovascular disease, and hypertension (Cook & Foster, 2012). | There are also risk factors associated with primary open-angle glaucoma. African people have a prevalence up to 5 times higher than other ethnic groups of developing glaucoma (Cook & Foster, 2012). You risk of developing glaucoma exponentially increases with age. Particularly, Hispanics have a more pronounced increased risk of developing glaucoma with age compared to other ethnic groups (Cook & Foster, 2012). Additionally, having a thin cornea and/or a large optic disc diameter has shown to increase one's risk for glaucoma. Other factors associated with higher risk is low physical activity, having cardiovascular disease, and hypertension (Cook & Foster, 2012). | ||
| - | <box 25% round | > {{ :wiki:omd_apr_3801.jpg?250 |}} </box| Figure 2: Projected estimates of people affected by glaucoma. (Retrieved from:)> | + | <box 25% round | > {{ :wiki:omd_apr_3801.jpg?250 |}} </box| Figure 2: Projected estimates of people affected by glaucoma. (Retrieved from: Glaucoma, 2019)> |
| ====== SYMPTOMS ====== | ====== SYMPTOMS ====== | ||
| + | Glaucoma, also known as the "silent thief" of sight, rarely causes symptoms until optic-nerve-fiber damages occurs, creating scotomas. The condition can develop in one or both eyes. Clinical features vary with the form of glaucoma. At first, there are no symptoms. Vision stays normal, and there is no pain. As the disease progresses, a person may notice the side vision gradually failing. That is, objects in front may still be seen clearly, but objects to the side may be missed. As glaucoma remains untreated, the person may miss objects to the side and out of the corner of their eye. Without treatment, the person will slowly lose their peripheral side vision. Over time, straight-ahead vision may decrease until no vision remains. The following are the most common features seen in most forms of glaucoma (Naklha, 2007). | ||
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| + | **Pain and Redness:** Rapid increase in pressure to very high levels leads to eye pain and redness. | ||
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| + | **Blurred Vision/Visual Field Loss:** This occurs as a result of damages to the retinal nerve fibers leading to arcuate scotoma, an inferior nerve-fiber-bundle defect. Central vision is spared initially and the person is unable to notice the defect. Vision may still be perfect even at the terminal stage of glaucomatous field loss (tunnel vision) (Naklha, 2007). | ||
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| + | **Elevated Interaocular Pressure:** Pressure and severity of glaucomatous damage determines the rate at which elevated intraocular oressure causes optic nerve damage. In general, pressures of 20 to 30mm Hg usually causes damage over several years, but pressures of 40 to 50mm Hg can lead to rapid visual loss and also deteriorate retinovascular occlusion (Naklha, 2007). | ||
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| + | **Rainbow-Colored Rings or Halos Perceived Around Lights and Cloudy Cornea:** Endothelial cells are continuously removing fluid to keep the cornea transparent. When pressure rises, the cornea becomes waterlogged, causing visual acuity to decrease and forming halos around lights (Naklha, 2007). | ||
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| + | Other clinical symptoms that have been observed in association with the different forms of glaucoma due to the rapid buildup of intraocular pressure include nausea and vomiting, headaches, cataract, photophobia, blepharospasm (involuntary blinking or spasm of the eyelids), strabismus (misalignment of the eyes), epiphoria (excessive tearing), and amblyopia (lazy eye) (Naklha, 2007). | ||
| <box 50% round | > {{ :wiki:life_sci_4m03_-_presentation_3_glaucoma_5.jpg?500 |}} </box| Figure 3: General symptoms of glaucoma.> | <box 50% round | > {{ :wiki:life_sci_4m03_-_presentation_3_glaucoma_5.jpg?500 |}} </box| Figure 3: General symptoms of glaucoma.> | ||
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| There are also some genetic risk factors associated with glaucoma that could increase the chance of an individual developing the disease. Family history is a well- established risk factor. Mutations in the MYOC gene is primarily responsible for open-angle glaucoma, this gene provides information to code for a protein called myocilin (Leske, 2007). Myocilin is found in the trabecular meshwork and in the ciliary body that regulates intraocular pressure. In addition, mutations in the CYP1B1 gene is often detected in people with primary congenital glaucoma. This gene codes for a cytochrome P40 protein which like myocilin is found in the trabecular meshwork and ciliary body and regulates intraocular pressure (Leske, 2007). Diabetes and high blood pressure can also be risk factors for glaucoma. | There are also some genetic risk factors associated with glaucoma that could increase the chance of an individual developing the disease. Family history is a well- established risk factor. Mutations in the MYOC gene is primarily responsible for open-angle glaucoma, this gene provides information to code for a protein called myocilin (Leske, 2007). Myocilin is found in the trabecular meshwork and in the ciliary body that regulates intraocular pressure. In addition, mutations in the CYP1B1 gene is often detected in people with primary congenital glaucoma. This gene codes for a cytochrome P40 protein which like myocilin is found in the trabecular meshwork and ciliary body and regulates intraocular pressure (Leske, 2007). Diabetes and high blood pressure can also be risk factors for glaucoma. | ||
| - | <box 30% round | > {{ :wiki:4333.png?300 |}} </box| Figure 4: Prevalence of glaucoma according to age and race. (Quigley, 1993)> | + | <box 30% round | > {{ :wiki:4333.png?300 |}} </box| Figure 4: Prevalence of glaucoma according to age and race. (Retrieved from: Quigley, 1993)> |
| ====== DIAGNOSIS ====== | ====== DIAGNOSIS ====== | ||
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| - | <box 50% round | > {{ :wiki:life_sci_4m03_-_presentation_3_glaucoma_2.jpg?500 |}} </box|Figure 6: Comparison between a healthy eye and a glaucomatous eye with elevated intraocular pressure. (Retrieved from “Glaucoma,” n.d.)> | + | <box 50% round | > {{ :wiki:life_sci_4m03_-_presentation_3_glaucoma_2.jpg?500 |}} </box|Figure 6: Comparison between a healthy eye and a glaucomatous eye with elevated intraocular pressure. (Retrieved from: “Glaucoma”, n.d.)> |
| ===== Elevated Intraocular Pressure ===== | ===== Elevated Intraocular Pressure ===== | ||
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| There is currently no cure for glaucoma. Treatment focuses on lowering the intraocular pressure to a level that is less likely to cause further optic nerve damage. Depending on your situation, your options may include prescription eye drops, oral medications, laser treatment, surgery or a combination of any of these. | There is currently no cure for glaucoma. Treatment focuses on lowering the intraocular pressure to a level that is less likely to cause further optic nerve damage. Depending on your situation, your options may include prescription eye drops, oral medications, laser treatment, surgery or a combination of any of these. | ||
| + | <box 50% round | > {{ :wiki:meds_2.png?500 |}} </box|Figure 7: List of medications used for treating glaucoma. (Retrieved from: Naklha, 2007)> | ||
| ===== Eye drops/Oral Medications ===== | ===== Eye drops/Oral Medications ===== | ||
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| In the early stages of its development, glaucoma can be treated with eye drops that decrease eye pressure by either increasing aqueous humour outflow of reducing the production of the fluid. One or more prescription eye drop medication can be prescribed to an individual with the condition (Sleath //et al//., 2011). In addition, these drugs are typically taken once a day, or sometimes twice per day for life (Sleath //et al//., 2011). Examples of the types of drugs that may be prescribed to an individual include prostaglandins, beta-blockers (also available in pill form), alpha-adrenergic agonists, carbonic anhydrase inhibitors (also available in pill form), rho kinase inhibitors, and cholinergic agents (Mayo Clinic, n.d.). If eye drops alone are insufficient in lowering eye pressure, individuals may also be prescribed oral medications (pills), yet these are less often used (Mayo Clinic, n.d.). | In the early stages of its development, glaucoma can be treated with eye drops that decrease eye pressure by either increasing aqueous humour outflow of reducing the production of the fluid. One or more prescription eye drop medication can be prescribed to an individual with the condition (Sleath //et al//., 2011). In addition, these drugs are typically taken once a day, or sometimes twice per day for life (Sleath //et al//., 2011). Examples of the types of drugs that may be prescribed to an individual include prostaglandins, beta-blockers (also available in pill form), alpha-adrenergic agonists, carbonic anhydrase inhibitors (also available in pill form), rho kinase inhibitors, and cholinergic agents (Mayo Clinic, n.d.). If eye drops alone are insufficient in lowering eye pressure, individuals may also be prescribed oral medications (pills), yet these are less often used (Mayo Clinic, n.d.). | ||
| - | <box 15% round | > {{ :wiki:4.png?150|}} </box| Figure 7: Betaxolol eye drop. This a selective beta receptor blocker used in the treatment of glaucoma. (Retrieved from: MD Supplies)> | + | <box 15% round | > {{ :wiki:4.png?150|}} </box| Figure 8: Betaxolol eye drop. This a selective beta receptor blocker used in the treatment of glaucoma. (Retrieved from: MD Supplies)> |
| ===== Laser/Intrusive Treatments ===== | ===== Laser/Intrusive Treatments ===== | ||
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| Treatment may also involve laser therapy or surgery to improve fluid drainage within the eye as a means of lowering eye pressure. The most common forms include: | Treatment may also involve laser therapy or surgery to improve fluid drainage within the eye as a means of lowering eye pressure. The most common forms include: | ||
| - | * Unordered List ItemSele ctive Laser Trabeculoplasty (SLT): Involves using a laser beam to open clogged channels in the trabecular meshwork (Latina & Tumbocon, 2012). This procedure is used when eye drop medications are not lowering the eye pressure enough or are causing significant side effects. It can also be used as initial treatment for glaucoma. | + | * Selective Laser Trabeculoplasty (SLT): Involves using a laser beam to open clogged channels in the trabecular meshwork (Latina & Tumbocon, 2012). This procedure is used when eye drop medications are not lowering the eye pressure enough or are causing significant side effects. It can also be used as an initial treatment for glaucoma. |
| * Laser Peripheral Iridotomy (LPI): Involves a laser being used to create an opening in the iris so that fluid can leave the angle of the eye more easily (He //et al//., 2007). LPI is the preferred procedure for treating glaucoma caused by a relative or absolute block of aqueous humour flow. LPI eliminates pupillary block by allowing the aqueous to pass directly from the posterior chamber into the anterior chamber, bypassing the pupil. | * Laser Peripheral Iridotomy (LPI): Involves a laser being used to create an opening in the iris so that fluid can leave the angle of the eye more easily (He //et al//., 2007). LPI is the preferred procedure for treating glaucoma caused by a relative or absolute block of aqueous humour flow. LPI eliminates pupillary block by allowing the aqueous to pass directly from the posterior chamber into the anterior chamber, bypassing the pupil. | ||
| - | * Unordered List ItemTrabeculectomy: Involves creating a small channel is to drain fluid from the eye into a reservoir located underneath the eye’s natural lining, the conjunctiva. This reservoir, known as a bleb, may appear like a blister-like bump on the white of the eye. Regarded as the “gold standard” in glaucoma surgery (Brandão & Grieshaber, 2013; Skuta & Parrish, 1987). Trabeculectomy is a standard surgery for lowering pressure inside the eye when medical treatments or laser surgery have failed to bring the eye pressure low enough. In this operation, a small hole is made in the wall of the eye, and a “trapdoor” or “flap” is created over this hole to allow fluid to escape the eye in a controlled fashion. The fluid is shunted from inside the eye, bypassing the obstructed trabecular meshwork, through the small hole and “trapdoor,” while remaining underneath the outer clear membrane of the eye (conjunctiva). This forms a small blister or “bleb” underneath the upper eyelid. Normally, no one will be able to see the “bleb” just by looking at the eyes. | + | * Trabeculectomy: Involves creating a small channel is to drain fluid from the eye into a reservoir located underneath the eye’s natural lining, the conjunctiva. This reservoir, known as a bleb, may appear like a blister-like bump on the white of the eye. Regarded as the “gold standard” in glaucoma surgery (Brandão & Grieshaber, 2013; Skuta & Parrish, 1987). Trabeculectomy is a standard surgery for lowering pressure inside the eye when medical treatments or laser surgery have failed to bring the eye pressure low enough. In this operation, a small hole is made in the wall of the eye, and a “trapdoor” or “flap” is created over this hole to allow fluid to escape the eye in a controlled fashion. The fluid is shunted from inside the eye, bypassing the obstructed trabecular meshwork, through the small hole and “trapdoor,” while remaining underneath the outer clear membrane of the eye (conjunctiva). This forms a small blister or “bleb” underneath the upper eyelid. Normally, no one will be able to see the “bleb” just by looking at the eyes. |
| * Tube-Shunt Surgery (Seton glaucoma surgery): Involves small tubes being inserted into the eye to drain away excess fluid and lower eye pressure (Eid & Augsburger, 1997). This type of surgery is usually done after a trabeculectomy has failed. | * Tube-Shunt Surgery (Seton glaucoma surgery): Involves small tubes being inserted into the eye to drain away excess fluid and lower eye pressure (Eid & Augsburger, 1997). This type of surgery is usually done after a trabeculectomy has failed. | ||
| - | <box 25% round | > {{ :wiki:5.png?250 |}} </box|Figure X. Tube shunt (arrow) as seen inside the eye in front of the brown iris (Retrieved from: John Hopkins Medicine)> | + | <box 25% round | > {{ :wiki:5.png?250 |}} </box|Figure 9: Tube shunt (arrow) as seen inside the eye in front of the brown iris. (Retrieved from: John Hopkins Medicine)> |
| ===== Future Treatment: Gene Therapy ===== | ===== Future Treatment: Gene Therapy ===== | ||
| - | There has been a lot of recent research on the use of gene therapy as a means of treating glaucoma. The idea behind gene therapy is to introduce an exogenous gene into a cell in order to modify its activity. Gene therapy is not used to fix defective genes, but to introduce a new gene which down or up-regulates a function of the receiving cell. This is accomplished through the use of inactivated (i.e., they do not express any other activity except the one of the gene of interest and its promoter) vectors (typically, viruses) that are unable to replicate (Fogagnolo & Rossetti, 2011). | + | There has been a lot of recent research on the use of gene therapy as a means of treating glaucoma.{{ :wiki:small-dna-gene_b.gif?250|}} The idea behind gene therapy is to introduce an exogenous gene into a cell in order to modify its activity. Gene therapy is not used to fix defective genes, but to introduce a new gene which down or up-regulates a function of the receiving cell. This is accomplished through the use of inactivated (i.e., they do not express any other activity except the one of the gene of interest and its promoter) vectors (typically, viruses) that are unable to replicate (Fogagnolo & Rossetti, 2011). |
| - | In a study conducted by Borrás and colleagues (2001), they investigated the effects on treating the eyes of monkeys with a protein,adenoviral vector expressing rat non-muscle caldesmon fused to green fluorescent protein. After 24-48 hours, trabecular meshwork cells had a change in activity and GFP-caldesmon was hyper-expressed. As a result aqueous humour outflow was increased by 50%. In another study by Borrás and colleagues (2010), they evaluated the effects of an adenoviral vector carrying the gene of metalloproteinase 1 when injected on living sheep before and after the induction of corticosteroids intraocular pressure. Sheep were chosen because they have a high corticosteroid response on intraocular pressure. In sheep with high eye pressure, the injection achieved pressure reductions up to 70% in 24 hours. In eyes with normal pressure, pre-injection protected against the increase in IOP which was induced by the continuous application of the corticosteroid for 5 days. | + | In a study conducted by Borrás and colleagues (2001), they investigated the effects of treating the eyes of monkeys with a protein, adenoviral vector expressing rat non-muscle caldesmon fused to green fluorescent protein. After 24-48 hours, trabecular meshwork cells had a change in activity and GFP-caldesmon was hyper-expressed. As a result, aqueous humour outflow was increased by 50%. In another study by Borrás and colleagues (2010), they evaluated the effects of an adenoviral vector carrying the gene of metalloproteinase 1 when injected on living sheep before and after the induction of corticosteroid ocular hypertension leading to intraocular pressure. Sheep were chosen because they have a high corticosteroid response on intraocular pressure. In sheep with high eye pressure, the injection achieved pressure reductions up to 70% in 24 hours. In eyes with normal pressure, pre-injection protected against the increase in IOP which was induced by the continuous application of the corticosteroid for 5 days. |
| - | While the research on gene therapy treatment for glaucoma is growing, and has been investigated with animal models, many important issues such as the long term efficacy and safety of using need to be considered before beginning //in vivo// human studies. | + | While the research on gene therapy treatment for glaucoma is growing and has been investigated with animal models, many important issues such as the long term efficacy and safety of using it as a mechanism of treatment need to be considered before beginning //in vivo// human studies. |
| ====== REFERENCES ====== | ====== REFERENCES ====== | ||
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| Glaucoma. (n.d.). Retrieved from https://fleetwoodfamilyeyecare.com/glaucoma/ | Glaucoma. (n.d.). Retrieved from https://fleetwoodfamilyeyecare.com/glaucoma/ | ||
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| + | Glaucoma: Open-angle. (2019). National Institutes of Health. Retrieved from: https://nei.nih.gov/eyedata/glaucoma | ||
| Harada, C., Kimura, A., Guo, X., Namekata, K., & Harada, T. (2019). Recent advances in genetically modified animal models of glaucoma and their roles in drug repositioning. //The British Journal of Ophthalmology//, 103(2), 161-166. | Harada, C., Kimura, A., Guo, X., Namekata, K., & Harada, T. (2019). Recent advances in genetically modified animal models of glaucoma and their roles in drug repositioning. //The British Journal of Ophthalmology//, 103(2), 161-166. | ||
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| MD Supplies. (n.d.). Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Retrieved from https://www.mdsupplies.com/medical-supplies-Betoptic-BETAXOLOL-HYDROCHLORIDE-Betaxolol-Ophthalmic-Solution-USP-05-5-mL-RLRDT6NWED.html | MD Supplies. (n.d.). Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Retrieved from https://www.mdsupplies.com/medical-supplies-Betoptic-BETAXOLOL-HYDROCHLORIDE-Betaxolol-Ophthalmic-Solution-USP-05-5-mL-RLRDT6NWED.html | ||
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| + | Naklha, E. (2007). Therapeutic options for glaucoma. //Journal of Modern Pharmacy//, 14(9), 14. Retrieved from: https://www.uspharmacist.com/article/therapeutic-options-for-glaucoma | ||
| Patel, S. C., & Spaeth, G. L. (1995). Compliance in patients prescribed eyedrops for glaucoma. //Ophthalmic Surgery, Lasers and Imaging Retina//, 26(3), 233-236. | Patel, S. C., & Spaeth, G. L. (1995). Compliance in patients prescribed eyedrops for glaucoma. //Ophthalmic Surgery, Lasers and Imaging Retina//, 26(3), 233-236. | ||
