Eye disease

Eye disease

The eye is a complex sensory organ responsible for sight. Injury or disease to the ocular system can result in vision loss. A variety of ophthalmic preparations (topical, parenteral, and oral) are available for both therapeutic and diagnostic use.  Medications play a key role in the management of chronic dry-eye, diabetic retinopathy, glaucoma, infection, inflammation, and macular degeneration.

The structural anatomy of the eye makes pharmacological treatment a unique challenge. The cornea consists of multiple layers comprised of hydrophobic and hydrophilic properties which can alter topical drug absorption. Although systemic absorption of ophthalmic agents can occur (mentioned in topics below), it is generally minimal as the eye is isolated from systemic vascular access due to the blood-retinal, blood-aqueous, and blood-vitreous barriers.

 

Figure 15.4a Internal Structure of the Eye (sagittal section) from: http://slideplayer.com/slide/3862142/ Marieb & Hoehn 9th ed. Chapter 15 The Special Senses. Pearson Education, Inc. 2013

 

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Drugs for Glaucoma

Glaucoma is a condition that involves damage to the optic nerve, often caused by elevated intraocular pressure. Inadequate drainage of aqueous humor within the anterior chamber of the eye places stress on the optic nerve tissue. The resulting nerve damage leads to peripheral vision loss (tunnel vision) and, eventually, total blindness. Drug therapy has shown to be effective in delaying progressive vision loss by decreasing the production or improving the drainage of aqueous humor.  

 

Glaucoma Medication Classes:

Prostaglandin Analogs attenuate intraocular pressure (IOP) by improving the outflow of aqueous humor. Prostaglandin analogs exhibit agonistic activity on FP prostanoid receptors, which promotes uveoscleral outflow. Medications within this class include latanoprost, travoprost, bimatoprost, tafluprost, and unoprostone isopropyl. These topical medications offer the greatest reduction in IOP. Prostaglandin analogs can cause undesirable cosmetic changes such as brown pigmentation of the iris, discoloration of the eyelids, and increased growth/thickness of eyelashes. Other adverse effects include blurred vision, eye irritation, itching, and headache.

 

β-Adrenoreceptor Antagonists administered topically can reduce IOP by decreasing aqueous humor production. Beta-blockers antagonize the effects of sympathetic neurotransmitters by inhibiting β1 and β2 receptors; however their mechanistic action in glaucoma is unclear. Examples include timolol, betaxolol, carteolol, and levobunolol. Adverse effects, when systemically absorbed can include bradycardia, hypotension, headache, decreased exercise tolerance, and bronchospasm but these systemic effects are rare.

 

Carbonic Anhydrase Inhibitors (CAIs) work by decreasing production of aqueous humor. Carbonic anhydrase is an enzyme that catalyzes the formation of bicarbonate from carbon dioxide and water (and vice-versa), with the most active isoform being carbonic anhydrase II. Inhibition of this isoenzyme within the ciliary epithelium slows the formation of bicarbonate ions; decreasing the extracellular transport of water necessary for aqueous humor production.

Dorzolamide and brinzolamide are topical medications within this class. Adverse effects include blurred vision and altered taste. Acetazolamide is administered orally and has a higher rate of IOP reduction when compared to topical CAIs. Notable adverse effects of oral therapy include electrolyte imbalance, metabolic acidosis, blood dyscrasias, serious allergic skin reactions, and formation of kidney stones. CAIs are contraindicated in those with sulfonamide allergies and the oral CAI should not be used by individuals with poor kidney/liver function.

 

α-Adrenoreceptor Agonists can be applied topically to decrease production of aqueous humor. Ophthalmic α2 agonists include brimonidine and apraclonidine. By activating α2 receptors in the ciliary epithelium, adenylyl cyclase becomes inhibited and cyclic adenosine monophosphate (cAMP) is no longer formed. This hinders ion transport and, thus, fluid production. Over time, these medications appear to improve fluid outflow as well. Adverse effects can include contact dermatitis, dry mouth, headache, hypotension, and somnolence. Use of α2 agonists is contraindicated with concurrent monoamine oxidase inhibitor (MAOI) therapy due to pronounced hypotension.

 

Parasympathomimetic Agents are topical cholinergic agonists that reduce IOP by improving fluid outflow through the trabecular meshwork. Activation of muscarinic (M3) receptors allows for contraction of ciliary muscle fibers, which expands the pores of the trabecular meshwork to enhance outflow. Ophthalmic agents within this class include carbachol and pilocarpine. Adverse effects include sweating, salivation, eye pain, blurred vision, abdominal pain, and headache. Parasympathomimetics are contraindicated in those with uncontrolled asthma.

Kelly Karpa, Anthony Possanza

This article was published by the American Academy of Ophthalmology to provide the general public with a comprehensive understanding of glaucoma. It is broken-down into several sections: Overview, symptoms, causes, risk factors, diagnosis, treatment, and simulation of visual deterioration. There are helpful videos embedded within these sections as well. Published by the American Academy of Ophthalmology: Peer-reviewed by Dr. J Kevin McKinney, MD

Beginner level

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Glaucoma is a condition that involves damage to the optic nerve, often caused by elevated intraocular pressure. Inadequate drainage of aqueous humor within the anterior chamber of the eye places stress on the optic nerve tissue. The resulting nerve damage leads to peripheral vision loss (tunnel vision) and, eventually, total blindness. Drug therapy has shown to be effective in delaying progressive vision loss by decreasing the production or improving the drainage of aqueous humor.  

 

Glaucoma Medication Classes:

Prostaglandin Analogs attenuate intraocular pressure (IOP) by improving the outflow of aqueous humor. Prostaglandin analogs exhibit agonistic activity on FP prostanoid receptors, which promotes uveoscleral outflow. Medications within this class include latanoprost, travoprost, bimatoprost, tafluprost, and unoprostone isopropyl. These topical medications offer the greatest reduction in IOP. Prostaglandin analogs can cause undesirable cosmetic changes such as brown pigmentation of the iris, discoloration of the eyelids, and increased growth/thickness of eyelashes. Other adverse effects include blurred vision, eye irritation, itching, and headache.

 

β-Adrenoreceptor Antagonists administered topically can reduce IOP by decreasing aqueous humor production. Beta-blockers antagonize the effects of sympathetic neurotransmitters by inhibiting β1 and β2 receptors; however their mechanistic action in glaucoma is unclear. Examples include timolol, betaxolol, carteolol, and levobunolol. Adverse effects, when systemically absorbed can include bradycardia, hypotension, headache, decreased exercise tolerance, and bronchospasm but these systemic effects are rare.

 

Carbonic Anhydrase Inhibitors (CAIs) work by decreasing production of aqueous humor. Carbonic anhydrase is an enzyme that catalyzes the formation of bicarbonate from carbon dioxide and water (and vice-versa), with the most active isoform being carbonic anhydrase II. Inhibition of this isoenzyme within the ciliary epithelium slows the formation of bicarbonate ions; decreasing the extracellular transport of water necessary for aqueous humor production.

Dorzolamide and brinzolamide are topical medications within this class. Adverse effects include blurred vision and altered taste. Acetazolamide is administered orally and has a higher rate of IOP reduction when compared to topical CAIs. Notable adverse effects of oral therapy include electrolyte imbalance, metabolic acidosis, blood dyscrasias, serious allergic skin reactions, and formation of kidney stones. CAIs are contraindicated in those with sulfonamide allergies and the oral CAI should not be used by individuals with poor kidney/liver function.

 

α-Adrenoreceptor Agonists can be applied topically to decrease production of aqueous humor. Ophthalmic α2 agonists include brimonidine and apraclonidine. By activating α2 receptors in the ciliary epithelium, adenylyl cyclase becomes inhibited and cyclic adenosine monophosphate (cAMP) is no longer formed. This hinders ion transport and, thus, fluid production. Over time, these medications appear to improve fluid outflow as well. Adverse effects can include contact dermatitis, dry mouth, headache, hypotension, and somnolence. Use of α2 agonists is contraindicated with concurrent monoamine oxidase inhibitor (MAOI) therapy due to pronounced hypotension.

 

Parasympathomimetic Agents are topical cholinergic agonists that reduce IOP by improving fluid outflow through the trabecular meshwork. Activation of muscarinic (M3) receptors allows for contraction of ciliary muscle fibers, which expands the pores of the trabecular meshwork to enhance outflow. Ophthalmic agents within this class include carbachol and pilocarpine. Adverse effects include sweating, salivation, eye pain, blurred vision, abdominal pain, and headache. Parasympathomimetics are contraindicated in those with uncontrolled asthma.

Kelly Karpa, Anthony Possanza

This 60 minute recorded open lecture on the topic of glaucoma was presented at UCSF. It provides a detailed overview of ocular anatomy, the pathophysiology of glaucoma (touches on cataracts and retinopathies as well), causes, risk factors, medical/surgical treatment options, and epidemiological research, followed by a Q&A session at the end. Dr. Shan Lin does an excellent job simplifying the material discussed throughout the presentation. Created by Dr. Shan Lin, Director of Glaucoma Service and Professor of Clinical Ophthalmology at  University of California- San Francisco (UCSF)

Prerequisite: The American Academy of Ophthalmology article on glaucoma: https://www.aao.org/eye-health/diseases/what-is-glaucoma

Intermediate/Advanced level

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