A Research about The Side Effects of Eye Local Anesthetics on The
Corneal Epithelium of Rabbits
Abstract
M.H.Haidari [1] Background: Topical anesthetics are chemical agents which A.Avand [2] are most common in ophthalmic practices including tonometry,
contact lens fitting and in such operations as cataract,
pterygium and etc.
The mechanism of the effect of these drugs is based on the
corneal epithelium. Most of agents modify neural impulses to
the iris muscle at the synapses and the effector sites. They
increase the absorption characteristics of mucous membrane.
The purpose of the present research was to study the effects
of tetracaine[3] 0.5%,a topical anesthetics, on the corneal
epithelium .
Materials and method:
While studying corneal mucous membrane , the researchers
used an SEM to show the effects of the drug on the cellular
junctions. To carry out the study, the researchers first
selected sixteen mature white Norwegian rabbits. They were
divided into one control and three experimental groups. The
former group received one, three and five drops of tetracaine0.5%
in twenty-minute time intervals respectively ,while the control
group only received as many drops of distilled water in the same
time interval instead. Second, all underwent general anesthesia and
their corneas were removed and immersed into special fixators.
Having processed the samples, the researchers magnified them
and then interpreted the magnified images histiologically.
Findings and discussion:
The findings showed that the more drops of the drug were
administered, the more severe and the greater the corneal epithelial
lesion would occur. The samples, electron microscopically
viewed, showed separation and disruption of intercellular junction,
destruction and loss of superficial microvilli, and desmosome
which eventually caused the removal of layers of corneal epithelial
cells.
The researchers suggest that the people be aware of side effects of
the drug and they be used more carefully for the prevention of
further corneal damage.
Introduction:
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owadays, as new and effective drugs are being used in medical and pharmacology colleges, proportionately their side effects and harmful outcomes including drug overdose and improper administration of the drugs have unfortunately increased. Among these drugs, which are used in ophthalmic practice and such professions as welding, turnery and those dealing with ultraviolet and infrared lights for the relief of ocular pain are eye topical anesthetics. One of these topical anesthetics is tetracaine, which is largely used in such cases as relieving the postoperative ocular pain and the removal of foreign particles embedded in the corneal epithelium.
Having observed this phenomenon, the researchers were motivated to do a research on the effect of the eye local anesthetics and to the extent to which it may impair corneal epithelium.
The transparent cornea, providing the eye with a clear refractive surface, tensile strength and protection from external factors has a simple design. It forms the anterior 1/6 of the eyeball. From anterior to posterior, it is composed of five concentric layers:
1) an outer epithelium held by an underlying basement membrane,
2) the cellular Bowman"s layer ,
3) the corneal stroma and
4) Descemet"s membrane onto which adheres
5) the corneal endothelium.
Measured externally, the cornea is oval-shaped, with average horizontal diameter 12.6 mm and 11.7 mm vertical diameter, though the dimensions vary considerably from one person to another.
Posteriorly, the cornea is concave and circular, measuring about 11.7 mm in diameter. The outer layer of the cornea is a stratified, non-keratinized, non-secretory epithelium and consists of five to seven layers of cells.
The anterior surface of the cornea represents the major refractive component of the eye. The central third center of the cornea is of a generally spherical contour. The more peripheral portion of the cornea is flatter, radially asymmetric and thicker (0.65 mm) than the central portion (0.5 to 0.6mm).
The coronal epithelium has the thickness of about 50 to 60 micrometer and continuous with conjunctival epithelium. It has been estimated that a complete turnover of corneal surface epithelium cells takes place every 7 days. New cells are formed by mitotic division in the bimbal basal cell layer.
The superficial pavement cells have very small microvilli, which are attached to their neighboring cells by multiple desmosomes. These cells play a major role in controlling the normal hydration of the cornea, both by a barrier function limiting access of water for the aqueous humor to the corneal stroma, and by an active transport mechanism.
Tetracaine is one of the most popular topical anesthetics and is used in 0.25-1 % solutions. Within a minute or two of instillation of one drop of 0.5% solution of tetracaine contact tonometry can be carried out painlessly.
Repeated instillation of even very weak concentration of topical anesthetics, including tetracaine, will intensify the tiny superficial corneal epithelial lesions commonly seen with the slit lamp microscope after use of these eye drops. Accordingly, they should not be prescribed even in very dilute concentration for home use in an attempt to get rid of ocular irritation.
Materials and Methods:
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irst, sixteen mature white Norwegian rabbits were selected. Second, they were divided into one control and three experimental groups. Those rabbits in experimental groups received one, three and five drops of 0.5% tetracaine during a twenty-minute time interval respectively. However, those rabbits in control group only received as many drops of distilled water in the same time interval instead. Then, all the rabbits underwent general anesthesia. They were dissected and their corneas were operated, removed and immersed into fixator solutions.
Having been immersed into fixator solution for 18 hours, their corneas were then dehydrated. After that, they were coated by gold. The processed corneas samples were then observed under electron microscope.
Both endothelium and epithelium are responsible for the transparency of the cornea. The two layers of cells are able to transport sodium ions to the superficial apical cell membrane, though corneal epithelium is a "tight" epithelium with a relatively low ionic conductance and a high resistance paracellular pathway.
Due to passive diffusion of chloride ions through these resistances, the transport process of corneal epithelium can promote dehydration of the cornea under certain conditions.
Corneal epithelium is dependent upon oxygen derived predominantly from the atmosphere. It has close connection with stroma metabolism. In order to maintain high metabolic rate of the epithelium, intact corneal innervations may play a role. Since the cornea is avascular and devoid of lymphatic drainage, it is necessary that nutritive requirements of the cornea be met by the atmosphere for the reception of oxygen by diffusion and tear film anteriorly and the aqueous humor posteriorly.
The absorption of ophthalmic drugs takes place in two stages: first, it dissolves in lipid and second, the dissolved lipid into water. Therefore, they should have both the property of the two stages.
Local anesthetics are regarded by most ophthalmic surgeons as the ideal for eye surgery. It can provide ocular akinesis, better controlling of the patient"s hyperventilation and good operating conditions. However, the occurrence of serious complications necessitates that the ophthalmic surgeon be aware of the resistance of an inflamed eye to local anesthetics, since the blood circulation in an inflamed eye causes the local anesthetics to move rapidly and as a result have conflicting demand on its pH which is necessary to avoid adverse effects, to produce therapeutic effect, to stabilize the preparation and to allow the preservative the correct conditions for action.
Biochemically, anesthetics may be arbitrarily classified into two main groups based on their metabolism by hydrolysis:
(1) esters and (2) amides
Tetracaine belongs to the latter, which is hydrolyzed in the tissue much more slowly than the former. Most amides are hydrolyzed more slowly than the corresponding esters.
Local anesthetics are chemical agents that reversibly block the transmission of nerve impulses along sensory fibers. In addition, they block motor nerves, but only at higher concentration than are normally obtained by topical instillation.
As with all topically applied drugs, there are local and systemic adverse effects. Before the drugs can reach the nerve fibers, they must first cross corneal epithelial cells. It has been found out that local anesthetics inhibit the cell growth and causes damage to the cell membrane and lots of microvilli as well as desquamation of the corneal epithelium when tetracaine 0.5% was applied to human cornea[4], which may be due to the inhibiting factor on calmodoline and the separation of vincaline-active complex.
Local anesthetics of ester type, such as Tetracaine, are hydrolyzed by bitycholine. Therefore, these drugs specifically are of a half-plasmic short life.
Discussion:
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he cornea has been known as the main pathway to the penetration of the eye through which superficial epithelial cells resist penetration by tight junction.
The permeability produced by surfactants in cornea is regarded as one the methods for facilitation of the absorption characteristics of drug agents. The recent studies have show that the preservatives present in chemical compounds of drugs cause damage to corneal epithelium. Accordingly, it is necessary to carry out careful studies on the effects of drug agents on the permeability and morphology of corneal epithelium as well as compounds prescribed.
In a study performed to determine the toxicity of topical anesthetics on the patients who underwent photoreactive keratotomy and were administered local anesthetics, the researchers showed that such anesthetics as Tetracaine and proprocaine decreased the viability of corneal cells; however, Tetracaine drastically lowered the cells than any other anesthetics. It was also found out that the toxicity depended upon the drug concentration and duration to which the patients were exposed.
In another study whose purpose was to assess the rate at which the local anesthetics were badly used, the researchers found out that they cause super infection by the candidates. Unless it is treated, it may lead to corneal epithelium damage.
The present study indicates that the local anesthetics misuse not only causes the destruction of superficial microvilli but also the degeneration of the cell junctions, which eventually brings about scar on the corneal surface. The researchers; in addition, have suggested that further studies be performed in order to focus on the chemical compounds of those anesthetics which produce less damage than overused present local anesthetics with severe side effects.
The Findings:
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he criterion adopted in this study was to determine the rate at which the consumption dose of tetracaine damaged the corneal epithelium cells while the duration and concentration of the drug agent was equally treated in all groups. It is worth saying that the previous studies also attributed the corneal damage to the duration and concentration of the drug.
The amount of the drug used was considered to be the prime deciding factor in causing the corneal damage among those who misused the drug to the extent that the more drops of the drug were administered, the more severe and the greater the corneal epithelial lesion would occur. In the case of drug overdose, it may however lead to scar on the corneal tissue.
The samples, electron microscopically viewed, showed separation and disruption of intercellular junction, destruction and loss of superficial microvilli, and desmosome which eventually caused the removal of layers of corneal epithelial cells.
As the drug dose gradually increased, say, one to five drops, proportionately the damage to the corneal epithelial cells would inevitably increase as well. The findings showed the significant correlation between the dose of tetracaine and the degree at which the corneal epithelium was hurt.
[1] - Assistant professor of Anatomy, Department of Anatomy, Fasa Medical College, Avecinna Square, Fasa, Fars Province, Iran
Email: haidarimh@fums.ac.ir . TEL-FAX:0098731222703
2- English lecturer , Department of Foreign languages, Fasa Medical College, Avecinna Square, Fasa, Fars Province, Iran
Email : avanda@fums.ac.ir.TEL-FAX:00987312220971
3 - The official name is Amethocaine.
[4] -Bolkja,M.;Kolar,G.;Videnesk,J.(1994).Influence of Topical Anesthetics on Tonometric Human Cornea
