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Glaucoma
What is Glaucoma?
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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
Aqueous Humor and IOP
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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
Epidemiology
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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
Who is affected/at risk?
Those at risk for the most common type include:
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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
Genetic link
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Glaucoma has been linked to a mutation in the GLC1A gene, found on chromosome
1
Types of Glaucoma
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4 main types:
Primary open angle (chronic) glaucoma
Angle closure (acute) glaucoma
Primary congenital glaucoma
Secondary glaucoma 5
Increased Intraocular Pressure
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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
Characteristic pattern to loss of visual field
Rim of optic nerve becomes
thinner as disc caves in and
becomes more cupped
Factors affecting acute angle closure glaucoma
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Anterior chambers gradually narrows,
cause greater resistance to flow
Symptoms
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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
Detection
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Complicated disease, several factors are not readily apparent even with tests
Tonometry
Ophthalmoscope
Visual field of vision test
Treatment
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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
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
Carbonic Anhydrase
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Carbonic anhydrase is an enzyme that
assists rapid inter-conversion of carbon
dioxide and water into carbonic acid, protons
and bicarbonate ions
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CO2 must be converted to bicarbonate for
aqueous humor production
Alpha carbonic anhydrase
Carbonic anhydrase mechanism for converting water and carbon dioxide to
bicarbonate
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3.
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Proton release from H2O; hydroxide ion
CO2 attracted to HO
HO + CO2 forms bicarbonate ion
Bicarbonate released, ready to repeat
Carbonic Acid Inhibitors
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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
Drozolamide Structural formula
Prognosis
Can only be managed
 Success depends on consistency and
compliance to drug
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References:
1)J.G. O’Shea, MD., Diagnosis and Management of Primary Open Angle Glaucoma
http://medweb.bham.ac.uk/easdec/eyetextbook/poag/poag.htm
2)Glaucoma Research Foundation http://www.glaucoma.org/learn/
3)Glaucoma entry in Wikipedia accessed April 24, 2006
4)-Genes and Diseases. Glaucoma.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=GLAUCOM
A+AND+gnd%5Bbook%5D+AND+138025%5Buid%5D&rid=gnd.section.127
5)Medical Encyclopedia, Glaucoma http://www.nlm.nih.gov/medlineplus/ency/article/001620.htm
6)Solomon, et al. Biology 7th Edition, 2005 Brookscole
7)Medicare Glaucoma Screening Benefit For Hispanic Americans
http://www.glaucomafoundation.org/news_story.php?i=37
8)Surgical Treatment of Open-Angle Glaucoma http://vision.about.com/od/glaucoma/a/glaucomatherapy_3.htm
9)What is Glaucoma
http://www.cipladoc.com/html/ophthalmology/medicalslides/immg/Innovations%20in%20medical%20management
%20of%20glaucoma.ppt#16
10)Glaucoma Australia, What is Glaucoma http://www.glaucoma.org.au/whatis.htm
11)S. Dutta, D.S. Goodsell, Carbonic Anhydrase January 2004
http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb49_1.html
12)Stryer, et al. Biochemistry 5th Edition. 2001 W. H. Freeman and Company
13)Carbonic anhydrase inhibitors for glaucoma
http://health.msn.com/encyclopedia/medications/articlepage.aspx?cp-documentid=100063787
14)Images- carbon anhydrase. oregonstate.edu/instruction/ bb450/lecturenote.
15)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=B6TF9-4J6248Y4&_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&m
d5=d9d4e286cbd2e29dacac57fce5a8f997&artImgPref=F
16)Image-http://www.suncoastretina.com/images/illustrations/AqueousFlow.jpg
17)image, http://www.lahey.org/Images/ExecutiveHealth/ExecHealthPersonal2.jpg