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Glaucoma

Glaucoma. What is Glaucoma?. Glaucoma refers to a group of diseases of the optic nerve Most cases involve increased fluid pressure, known as intraocular pressure (IOP) But increased IOP may not necessarily be cause, 20% have normal tension glaucoma

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Glaucoma

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  1. Glaucoma

  2. What is Glaucoma? • Glaucoma refers to a group of diseases of the optic nerve • Most cases involve increased fluid pressure, known as intraocular pressure (IOP) • But increased IOP may not necessarily be cause, 20% have normal tension glaucoma • Gradual loss of vision, can progress to blindness if untreated

  3. Aqueous Humor and IOP • Aqueous humor produced by ciliary body • Maintains shape of eye and has refractive properties • Drains through trabecular meshwork to Schlemm’s canal and then to venous system • IOP caused by resistance of flow of aqueous fluid • Avg. IOP is about 16 mm Hg • Fluctuates by as much as 6 mm Hg through day

  4. Epidemiology • Third leading cause of blindness worldwide • 22.5 million affected, estimated more than 5 million blind • In America, it’s the leading cause of blindness • 3 million affected

  5. Who is affected/at risk? Those at risk for the most common type include: • Everyone is at risk for developing glaucoma • High prevalence in African Americans • Also in Hispanics • People over 60 • Family history of disease • People with high near-sightedness (myopia) • Those with diabetes, hypertension, and thin corneas

  6. Genetic link • Glaucoma has been linked to a mutation in the GLC1A gene, found on chromosome 1

  7. Types of Glaucoma 4 main types: • Primary open angle (chronic) glaucoma • Angle closure (acute) glaucoma • Primary congenital glaucoma • Secondary glaucoma 5

  8. Increased Intraocular Pressure • Trabecular meshwork goes through glaucomatous changes • Changes affect outflow and lead to ocular hypertension • Increased IOP defined as greater than 21 mm Hg • Pressure affects flow of blood to optic nerve

  9. Characteristic pattern to loss of visual field Rim of optic nerve becomes thinner as disc caves in and becomes more cupped

  10. Factors affecting acute angle closure glaucoma • Anterior chambers gradually narrows, cause greater resistance to flow

  11. Symptoms • Most people don’t have symptoms, 50% of those that have glaucoma don’t know it • Gradual loss of peripheral vision • Blind spots • Loss of vision is hard to detect till it has already done some damage

  12. Detection • Complicated disease, several factors are not readily apparent even with tests • Tonometry • Ophthalmoscope • Visual field of vision test

  13. Treatment • No cure, only preventing further damage • Mainstay treatment is to target intraocular pressure • Topically applied drugs, as well as oral and intravenous • Drugs include adrenergic receptor antagonists, alpha2-adrenergic agonists, symphathomimetics, miotic agents (parasympathomimetics), prostaglandin analogs, and carbonic anhydrase inhibitors • Surgery aimed at trabecular meshwork or drain fluid • Laser trabeculoplasty • Conventional, trabeculectomy

  14. Controversy over Marijuana • Studies showed link to lower IOP in 1978 • Derivatives lowered IOP orally, intravenously, or by smoking; not topically • However, no advantage shown over other glaucoma drugs • More harm than good

  15. Carbonic Anhydrase • Carbonic anhydrase is an enzyme that assists rapid inter-conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions • CO2 must be converted to bicarbonate for aqueous humor production

  16. Alpha carbonic anhydrase

  17. Carbonic anhydrase mechanism for converting water and carbon dioxide to bicarbonate • Proton release from H2O; hydroxide ion • CO2 attracted to HO • HO + CO2 forms bicarbonate ion • Bicarbonate released, ready to repeat

  18. Carbonic Acid Inhibitors • Sulfonamides high affinity for many α-CA isozymes • Compete with water and bind to zinc • dorzolamide is a weaker derivative of Sulfonamides • Popular medication is Trusopt • Reduces fluid made in the eyes by 40% to 60%. • Accelerated blood velocity to optic nerve, improves visual function

  19. Drozolamide Structural formula

  20. Prognosis • Can only be managed • Success depends on consistency and compliance to drug

  21. References: • J.G. O’Shea, MD., Diagnosis and Management of Primary Open Angle Glaucomahttp://medweb.bham.ac.uk/easdec/eyetextbook/poag/poag.htm • Glaucoma Research Foundation http://www.glaucoma.org/learn/ • Glaucoma entry in Wikipedia accessed April 24, 2006 • -Genes and Diseases. Glaucoma. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=GLAUCOMA+AND+gnd%5Bbook%5D+AND+138025%5Buid%5D&rid=gnd.section.127 • Medical Encyclopedia, Glaucoma http://www.nlm.nih.gov/medlineplus/ency/article/001620.htm • Solomon, et al. Biology 7th Edition, 2005 Brookscole • Medicare Glaucoma Screening Benefit For Hispanic Americans http://www.glaucomafoundation.org/news_story.php?i=37 • Surgical Treatment of Open-Angle Glaucoma http://vision.about.com/od/glaucoma/a/glaucomatherapy_3.htm • What is Glaucoma http://www.cipladoc.com/html/ophthalmology/medicalslides/immg/Innovations%20in%20medical%20management%20of%20glaucoma.ppt#16 • Glaucoma Australia, What is Glaucomahttp://www.glaucoma.org.au/whatis.htm • S. Dutta, D.S. Goodsell, Carbonic Anhydrase January 2004http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb49_1.html • Stryer, et al. Biochemistry 5th Edition. 2001 W. H. Freeman and Company • Carbonic anhydrase inhibitors for glaucoma http://health.msn.com/encyclopedia/medications/articlepage.aspx?cp-documentid=100063787 • Images- carbon anhydrase. oregonstate.edu/instruction/ bb450/lecturenote. • Nishimori, I., et. al Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylorihttp ://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TF9-4J6248Y-4&_user=526750&_coverDate=04%2F15%2F2006&_alid=395427632&_rdoc=1&_fmt=full&_orig=search&_qd=1&_cdi=5221&_sort=d&_docanchor=&view=c&_acct=C000023759&_version=1&_urlVersion=0&_userid=526750&md5=d9d4e286cbd2e29dacac57fce5a8f997&artImgPref=F • Image-http://www.suncoastretina.com/images/illustrations/AqueousFlow.jpg • image, http://www.lahey.org/Images/ExecutiveHealth/ExecHealthPersonal2.jpg

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