1-Ocular therapeutics

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I-OCULAR PHARMACOLOGY & THERAPEUTICS

FACTORS AFFECTING SELECTION OF THE DRUG

1-The penetrating power of the drug to the intact corneal epithelium and blood aqueous barrier

2-The target site of drug within the eye, cornea, anterior chamber, vitreous chamber etc…

3-The stability of the drug and durability of its action

FACTORS AFFECTING CHOICE of ROUT of ADMINSTERATION

1-The drug character

2-Understanding of the ocular disease and knowledge of ocular barriers

It should be kept in mind that the route of administration of the ophthalmic drug has the same importance as the choice of the drug itself. Generally speaking, diseases of the conjunctiva, superficial cornea and eyelids may be corrected with topical or subconjunctival application, while diseases of the uveal system, anterior and posterior segments, orbit and lacrimal glands may be managed by topical, subconjunctival, retro-bulbar, and systemic administrations.

Ocular drugs usually administered topically and directly into the eye, and topical means application of the drug in a direct contact with the surface of the cornea and conjunctiva.

FACTORS AFFECTING PENETRATION POWER OF THE DRUG

I-DRUG CHARACTERISTICS

1-CHEMICAL CHARACTERS OF THE DRUG

The drug penetrates the cornea by differential solubility and not by simple diffusion. Certain drugs have high power to penetrate the cornea, others poorly penetrate the cornea, and the rest are unable to penetrate the cornea.

2-SIZE OF THE MOLOCULE

The size of the molecule has inverse relationship to the penetration power, small sized molecules penetrate the cornea faster and more efficient than larger ones.

3-DRUG CONCENTRATION

Drug concentration has direct relationship with penetration power, the higher the drug concentration the higher the penetration, but this concentration should be with the limit that can’t produce eye irritation by its high osmotic pressure.

II-VEHECLE OF THE DRUG

According to the vehicle of the drug, medical preparations are presented as one of the following

1-DROPS

Least irritating form with short topical duration, accordingly it increases the frequency of medication, most of eye drops administered every 0.5-2 hours. This frequent medication sometimes is impossible with viscous animals or those of bad tempers, by then other forms of medication are preferred like ointments. The number of drops applied to the eye shouldn’t be so high, as this high amount will stimulate the lacrimation and predisposes to rapid elimination of the drug from the eye, accordingly the drops should be administered as 1-2 drops every minutes two or three times each medication. This will insure no lacrimal stimulation and drug elimination.

2-OINTMENTS

They cause some irritation but they have longer duration than drops. Sometimes they are used at night only to reduce the unease feeling of patient.

3-POWDERS

They are too much irritating, as the particles of the powder cause friction to the highly enervated cornea.

Types of vehicles for drops and ointments are aqueous methylcellulose, hydroxyl ethyl cellulose, polyvinyl alcohol, and artificial mucin. After topical application, the drug may pass away with the tears to outside or to the nasolacrimal duct, or penetrate the cornea and/or conjunctiva.

ROUTS OF SDMINSTERATION

I-TOPICAL ADMINISTRATION OF DRUG

1-PERIODIC ADMINSTERATION

The medication is applied to the lower conjunctival cul-de-sac by applying thumb pressure at the base of the lower eyelid for rolling it out, 1-2 drops are applied, the animal is left for 1 min, then another 1-2 drops are applied. This insures absence of lacrimal stimulation and flushing of the drug.

2-SUB-PALPEBRAL ADMINSTERATION (sub-palpebral lavage)

Many horses with ocular injuries or diseases have painful eyes and resist application of topical medication. Fractious or unbroken horses and foals are particularly difficult to handle. Often owners are unable to apply topical medication to the eye of a horse because of the strong orbicularis muscle and the difficulty of simultaneously applying restraint and administering medication. Consequently, ocular lavage systems have been described to facilitate frequent intermittent or continuous administration of topical ophthalmic medication.

Technique: -

Sedate the patient, induce auriculopalpebral nerve block, shave the hair from the upper eyelid at the orbital rim and use povidone iodine soap to cleanse, inject lidocaine or similar local anesthetic subcutaneously in the shaved region, place ophthalmic proparacaine or similar topical anesthetic in the eye, with gloved hand insert the needle (trochar) under the upper eyelid, then through the palpebral conjunctiva and eyelid skin at a point near the orbital rim and about midway along the length of the upper eyelid, insert the lavage tubing through the needle (trochar), going from the inner (conjunctival) to the outer (skin) side, pull the needle (trochar) and tubing through the skin and then remove the needle by pulling it along the tubing and off the end, apply the multiple injection port and tape the tube and port to a tongue depressor to make the unit rigid, then tape this to the mane, for added security, a piece of tape can be applied to the tubing flush with the point at which the tubing exits the skin in order to prevent the tubing sliding inward.

3-NASOLACRIMAL LAVAGE SYSTEM

It is a method, through which the drug is periodically injected retrograde through the nasal punctum by a tube and a syringe, or a stent tube is placed temporarily into the nasolacrimal duct (NLD) through the nasal punctum and the drug is periodically injected through this tube by a syringe. This method is suitable for both treatment of inflammation and obstruction of the NLD or topical administration of drug to the corneo-conjunctival lesions

II-SUBCONJUNCTIVAL ADMINISTRATION

This procedure is indicated when sustained, high concentrations of medication are needed such as with stubborn corneal disease (e.g., pannus), anterior uveitis, or scleritis. Other disadvantages apart from problems associated with the medication itself include the risk of introduction of infection and the temporary pain associated with the injection. However, these usually are not significant.

Technique: -

Most patients can be injected without general anesthesia or sedation. A topical anesthetic is necessary. You should use appropriate restraint for the species in question (on side for dogs and cats, a twitch and auriculopalpebral nerve block for horses, nose tongs for cattle). The injection is given under the bulbar conjunctiva. It is important that the injection be placed as close to the lesion site as practical because this increases effectiveness. For example, in pannus the lesion usually is most prominent ventrolaterally and the injection should be directed there. Raise the upper eyelid. A 25 or 27 gauge needle is used. The needle (with syringe attached) should be directed tangential to the globe so that you will not penetrate the globe. The syringe should be held so that you can make the injection the moment you are under the conjunctiva; trying to change the position of your hand at this time may cause the needle to come out. You also should be resting the hand holding the syringe against the patient's head (or your other hand which is against the patient's head) so that if the head moves, your hand and syringe move together with the head rather than in opposite directions. A quick thrust is used to enter the conjunctiva and the injection is made; you must use a quick thrust because of the tendency for the globe to rotate away from you. Inject up to ½ ml in small animals and 1 ml in large animals. The therapeutic benefit from this type of injection lasts from several hours to several weeks depending on the agent used.

Advantages: -

1-Bypasseing the lipoidal epithelial barriers of the cornea and conjunctiva

2-Achieveing high intra-ocular drug level in a short time

3-Achieveing excellent intra-ocular absorption of the drug

Disadvantages: -

Inflammation, necrosis, hemorrhage and abscess formation at the seat of injection

Injection of the drugs sub-conjunctively at the base of the third eyelid is used but penetration of the globe and intra-ocular injections of the drug by mistake are serious complications.

III-INTRAVITREAL INJECTION

The anatomical barriers of ocular tissues and the characteristics of the vitreous body are responsible for poor penetration of drugs into the vitreous humour. Direct injection into the vitreous is a method for achieving high concentration of the drug in vitreous body. The technique can be performed by using short 22-25 gauges needle with 1 ml syringe that is inserted at the ora lineata posterior to limbus and directed towards the posterior pole of the eye.

Indication: -

Diffuse posterior segment inflammatory disease

IV-RETROBULBAR INJECTION

Local analgesic solutions are often injected around the muscles behind the globe for exenterating the orbital cavity in cattle. A long needle is used for injection of the anesthetic solution at four sites adjacent to the globe at 3, 6, 9 & 12 O'clock, while in equine the retro-bulbar injection is performed through the supra-orbital fossa. Antibiotics are sometimes injected by this route for intra-ocular infections, or retro-bulbar cellulites or abscess, as the sclera does not act as a barrier for drug penetration as does the cornea.

V-INTRAOCULAR INJECTION (INTRACAMERAL)

Injection of the drug into the anterior chamber through the limbus is indicated during surgery (to control hemorrhage or pupil size) and in the management of intra-ocular inflammatory disease. The procedure is performed under aseptic condition. During intra-ocular surgery sterile saline can be used to irrigate blood and fibrin out the eye.

VI-PARENTERAL ADMINISTRATION (SYSTEMIC)

Oral, intravenous, and intramuscular routes are used for treatment diseases of the posterior and anterior segment of the globe, orbit, sclera and eyelids. However, the used drugs should be able to penetrate the blood aqueous barrier

OPHTHALMIC THERAPEUTIC AGENTS

I-CLEANSING SOLUTIONS, EYE WASHES OR COLLYRIA

The use of tap water as eyewash is not recommended, and the eyewash is used for flushing the conjunctival sac and removal of ocular discharge, foreign bodies and irritants. Cleansing solution should be used worm or at room temperature. Application is accomplished by eyedropper, soft-rubber bulb syringe or plastic irrigating bottle. These fluids include

1-Normal saline solution

2-B.S.S. (Balanced salt solution)

3-Boric acid solution 2%

II-ASTRINGENTS

Astringents are locally acting protein precipitants, and they are occasionally used in various forms of conjunctivitis.

1-ZINC SULFATE

Zinc sulfate is the inorganic compound with the formula ZnSO4, it can be used as solution (0.2 - 0.25%) and ointment (0.5%) and it has mild astringent and antiseptic properties. It is used for mild non-specific conjunctivitis and is often combined with vasoconstrictor and antihistaminic drugs.

2-SILVER NITRATE

Silver nitrate solution (1%) is brushed to the everted eyelids and conjunctiva in various forms of conjunctivitis, as a result of its ability to kill microorganisms. It is very irritating drug and its use in veterinary ophthalmology is completely outmoded. It can be sued as stick for touching corneal ulcers for cauterization and stimulation of sloughing of necrotic tissues.

3-COPPER SULFATE

It is used for the removal of lymphoid follicles in chronic follicular conjunctivitis, and mainly used in crystal form. The palpebral and bulbar surfaces of the nictitating membrane may be rubbed lightly with the crystal and the eye immediately flooded with normal saline solution.

4-YELLOW MERCURIC OXIDE (golden eye ointment)

This is an outmoded agent that was used for its antiseptic properties. It is employed in an ointment (1-3%) and useful for blepharitis, chronic conjunctivitis and superficial punctate keratitis.

III-CAUTERIZING AGENTS

Cauterizing substances are those substances used to destroy tissue for medical reasons, these cauterants are severe protein-precipitating agents that cause tissue destruction and are used to remove necrotic tissues and debris.

1-CARBOLIC ACID (phenol)

It is used safely used for cauterization of corneal ulcer and producing corneal sloughs as the corneal protein is quickly precipitated by the acid and in turn acts as a barrier for further penetration of acid into deeper layers of the cornea and destruction of these deeper layers.

2-TINCTURE IODINE

Iodine is a milder cautrant than phenol, used for cauterization of corneal ulcers. Tincture of iodine (3-7%) may be used for treatment of superficial corneal erosion, however it had been replaced by surgical superficial keratectomy in dogs.

3-TRICHLOROACETIC ACID

Trichloroacetic acid 25% solution is a powerful cauterizing substance used for cauterization of corneal ulcer and fistulae

4-Silver Nitrate Sticks

It is a dangerous cauterizing agent and it must be neutralized, after touching of the cornea, by sodium chloride solution to precipitate the silver as silver chloride, to avoid further reaction with the cornea and irreversible damage.

IV-MYDRIATICS AND CYCLOPLEGICS

Mydriatics

They are agents that produce dilatation of the pupil by induction of paralysis of circular muscle without affecting radiating muscle or stimulate contraction of radiating muscle, with resultant increase in the size of the pupil.

Cyloplegics

They are agents that cause paralysis of the ciliary body with resulting dilatation of the pupil, this paralysis of ciliary body and its muscles, relieve pain of the eye induced by spasm of ciliary muscles. Thus cycloplegics act as mydriatics but a mydriatic does not necessarily cause cycloplegia.

1-PARASYMPATHOLYTIC DRUGS (anticholinergic drugs)

These drugs produce dilatation of the pupil and cycloplegia

A-ATROPINE

Atropine sulfate, solution or ointment, is one of the most important mydriatic cycloplegic in veterinary ophthalmology. Atropine is not frequently used as a mydriatic for examination because its action lasts for more than 24 hours. Moreover, it is contraindicated in breeds susceptible to glaucoma, in cases of lens luxation, in animals affected with keratitis sicca. Moreover, its use in high dose in equine may lead to absorption and systemic reaction like paralysis of GIT, or blurred vision and its associating bad temper.

Indications: -

1-Ophthalmoscopic examination, to view the fundus of the eye

2-Iritis, cyclitis or anterior uveitis, to relieve painful spasm by relaxing ciliary muscle

3-Deep keratitis and corneal ulceration, as mydriasis may lower IOP and prevent rupture of the ulcer

B-TROPICAMIDE (1% solution)

It is a fast acting drug, of short duration, used to induce mydriasis for intraocular ophthalmoscopy. A maximum mydriasis is obtained within 20-30 minutes and the pupil will return to normal within several hours.

C-SCOPOLAMINE (0.3-0.5%)

Sometimes it is used before intra-ocular surgery.

2-SYMPATHATIC DRUGS

The common drugs in this group are adrenaline and phenylephrine. They do not cause cycloplegia and their effect is upon the dilator muscle of the iris.

A-ADRENALINE (Epinephrine)

Indications: -

1-Break down of recent synechia

2-Vasoconstriction for control of hemorrhage in the eye originated from the iris, or blood vessels of the conjunctive or sclera, as it stimulates contraction of vascular smooth muscle, resulting in vasoconstriction.

3-Reduction of the process of drugs absorption

B-PHENYLEPHRINE

It is used as mydriatic in 10% solution for ophthalmoscopy and in the treatment of minor allergic and inflammatory conjunctival disorders

V-MIOTICS

Miotics are drugs that constrict the pupil. They may be used in the treatment of glaucoma or after a mydriatic examination. Miotics are either parasympathomimetic (cholinergic-stimulating) drugs which have a direct muscarinic action, such as pilocarpine and carbachol, or anticholinesterase drugs which block the effect of acetylcholinesterase thus letting acetylcholine produce its effect, such as physostigmine, neostigmine, echothiophate and demecarium. There are also some miotics which act by blocking α-or β-adrenergic receptors. For example, dapiprazole and thymoxamine block the α-adrenergic receptors and propranolol blocks the β-adrenergic receptors.

1-DIRECT ACTING MIOTICS

Cholinergic drugs which stimulate the effect of acetylcholine as pilocarpine, acetylcholine and carbachol.

2-INDIRECT ACTING MIOTICS

Anticholinesterases drugs, which prevent the hydrolysis of acetylcholine by the enzyme cholinesterase, they include phospholine iodide, fluoropryl, humorsol and eserine.

Indications: -

1-Reduction of IOP in case of glaucoma by their topical instillation leading to increased outflow of aqueous

2-Stimulate secretory glands (lacrimator) in case of keratoconjunctivitis sicca

3-Induction of miosis after application of mydriasis

VI-LOCAL ANESTHETICS OR ANALGESICS

A number of diagnostic and surgical procedures can be performed in veterinary ophthalmology under the effect of local anesthesia. Instillation of topical anesthetic is used for minor diagnostic and surgical processes that require superficial manipulation of the cornea and conjunctiva such as tonometry, gonioscopy, foreign body removal, suture removal, conjunctival follicles removal, conjunctival scraping, and corneal ulcer cauterization. More detailed surgical procedures such as third eyelid flap, conjunctival flap, repair of eyelid laceration and removal of eyelid neoplasms can be achieved with nerve block and local tissue infiltration. Tranquilization may be essential to facilitate instillation of topical anesthetics, nerve block and local infiltration.

1-TOPICAL ANALGESICIS

Variations among them depend on

1-Time of onset

2-Duration of action

3-Stability

4-Local and systemic toxicity

Nearly all of them inhibit corneal epithelial healing in variable degrees

Marked healing inhibition

1-Cocaine 2%                 

2-Cornacaine 2%.

Slight delay of healing

1-Lignocaine 4%              

2-Pontocaine (Tetracaine®) 4%            

3-Proparacaine (Ophthaine®) 2%

No delay of healing

1-Lidocaine 2% (Xylocaine®)                 

2-Metycaine 2%. (Piperocaine®)

CONSIDERATIONS ON USE OF TOPICAL ANESTHETICS

1-Local anesthetics should not be used therapeutically or included in any therapeutic preparation

2-Most of them are toxic to normal corneal epithelium and inhibit corneal regeneration

3-Bacterial samples should be taken before application of topical anesthetics as the anesthetic drug and its preservative will kill the bacteria in conjunctival sac that interfere with sensitivity test results

4-Topical anesthetics are unsuitable for local infiltration

5-Some of them is extremely toxic

2-INJECTABLE ANALGESICIS

Local infiltration and nerve block (regional anesthesia) are useful in veterinary ophthalmology for examination and minor surgical procedures especially in large animals. The most common injectable anesthetics are Lidocaine 1-2% (Xylocaine®) and Procaine1% (Novocaine®).

VII-ANTIBIOTICS

Antibiotics are the most commonly used drugs in veterinary ophthalmology. Unfortunately, its misuse is nearly as great as its benefits. Antibiotics are prescribed before specific diagnosis has been established. Before application of antibiotics, the clinician should be certain that the inflammation is infectious and not due to trauma, foreign body, mechanical or chemical irritation, allergy, contact sensitivity and degenerative or metabolic disease. In external infection of the eye, a smear should be prepared before application of antibiotics. In acute severe and chronic infected cases, culture and sensitivity test should be performed. Antibiotics may be administered until the results of the sensitivity test is determined

FACTORSAFFECTING SELECTION OF ANTIBIOTIC

The ideal basis for selection of antibiotic is the identification of the responsible organism and its antibiotic sensitivity, and combination of different antibiotics should be synergistic and not antagonistic. However selection of suitable antibiotic depends up on the following

1-The nature of the causative organism and its sensitivity to the antibiotic

2-The spectrum of activity of the antibiotic

3-The penetrating properties of the antibiotic into the eye through the intact corneal epithelium and blood-aqueous barrier

4-The pharmacologic and toxic properties of the antibiotic

ADVANTAGES OF COMBINATION OF ANTIBIOTICS

1-The ability to provide broader spectrum coverage than one antibiotic

3-It insures the sensitivity to other antibiotics if the organism developed resistance to one of them

2-It permits the use of sub-toxic dose if one of them is highly toxic

THE MOST IMPORTANT OCULAR ANTIBIOTICS

1-ANTIBIOTICA CAN’T PASS CORNEAL EPITHELIUM

These are antibiotics that can’t penetrate intact corneal epithelium and blood-aqueous barrier as streptomycin, terramycin, and penicillins and its derivatives except ampicillin. Intraocular penetration of these drugs is very poor even if they were injected sub-conjunctively, and they can’t cross the blood-aqueous barrier unless administered in high doses, accordingly these drugs can be used for superficial eye disease.

2-ANTIBIOTICA CAN PASS CORNEAL EPITHELIUM

These are antibiotics, which have the power to penetrate the intact corneal epithelium and cross the blood-aqueous barrier as chloramphenicol, neomycin, bacitracin and gentamycin. Chloramphenicol is a broad-spectrum antibiotic, effective against a wide variety of gram-positive and gram-negative organisms, and it is one of the most effective drugs for ocular infection. Chloramphenicol can be used topically, sub-conjunctively, intravenously and orally. Neomycin, bacitracin and gentamycin are broad-spectrum antibiotics effective for the treatment of superficial ocular infections.

VIII-ANTIVIRAL DRUGS

Viruses are obligate intracellular parasites that utilize the metabolic processes of the host's cells. The location of the virus and intimate relationship to the host make effective therapy difficult. Idoxuridine (IDU) is chemically very similar to thymidine, one of the constituents of nucleic acid. IDU substitutes for thymidine in DNA synthesis and thus inhibits the action of the virus. Antiviral drugs are used for treatment of herpes keratoconjunctivitis, follicular conjunctivitis and superficial punctate keratitis in dogs and cats.

IX-ANTIFUNGAL AGENTS

Any non-specific corneal ulcer associated with corneal opacity that does not respond to antibiotic therapy should be scraped, stained and cultured for possible mycotic involvement. Superficial keratectomy of infected corneal tissues is often as effective as drug therapy and should be combined with it. It should be kept in mind that the use of antibiotics for long periods may kill beneficial bacteria in the eye and in turn stimulate growth of mycotics. Topical antimycotics are nystatin, amphotercin B, and natamycin. However, mycotic infection of the eye may involve

1-Infection of the skin of the eyelids "blepharodermatomycosis"

2-Mycotic keratitis following corneal injuries by foreign vegetable objects

3-Intraocular infection leads to mycotic endophthalmitis

X-SULPHONAMIDES

Sulphonamides have largely been replaced by antibiotics but still useful for minor infection. They are bacteriostatic and act by blocking utilization of para-aminobenzoic acid (PABA) by bacteria. Purulent exudate that contains para-aminobenzoic acid interferes, with the action of sulfonamides. Sulfa drugs are effective against gram-positive and some gram-negative organisms, and in higher concentration, against some viruses, fungi and toxoplasma. These drugs have a tendency to retard healing of corneal epithelium. Local anesthetics inhibit the effect of sulfas because topical anesthetics are esters of para-aminobenzoic acid.

XI-ANTI-INFLAMMATORIES

Anti-inflammatories are generally classified into non-steroidal and steroidal anti-inflammatories.

1-NON-STEROIDAL

These drugs involve aspirin (acetyl salicylic acid), Declophen, Ketoprofen, or Flunixin meglumine. They have analgesic, anti-pyritic, anti-inflammatory action, and have no adverse effect on immune system like steroidals.

2-CORTICOSTEROIDS

Corticosteroids are anti-inflammatories that affect the tissue response to causative agents rather than affecting the causative agents. They have analgesic effect but at the same time they have many adverse effects on the immune system and healing of wounds.

OCULAR EFFECTS OF CORTICOSTEROIDS

1-Suppress the inflammatory process by decreasing capillary dilatation, capillary permeability, exudation and the migration of the phagocytes to the site of inflammation.

2-Suppress scar formation of the cornea by inhibition of the process of collagen formation and reduction of the fibroblast activity

3-Suppress neovascularization (capillary proliferation) of the cornea

4-Suppress hypersensitivity reactions by inhibiting release of histamine from sensitized mast cell

5-Stimulation of collagenase enzyme that enhance break down of collagen bundles, accordingly it shouldn’t be used with corneal ulcers

6-They retard epithelial and endothelial regeneration of the cornea, thus delaying the normal wound healing process.

METHODS OF CORTICOSTEROIDS APPLICATION

A-Topical and Sub-conjunctival Injections

These methods offer numerous advantages over systemic administration as it achieves high local concentration for long periods with minimal systemic side effect. Hydrocortisone solution 2%, prednisolone 0.25%, and dexamethasone solution 0.1% are the most common corticosteroids used for topical and subconjunctival injections.

Indications: -

1-Blepharitis             

2-Non-pyogenic conjunctivitis

3-Superficial keratitis

4-Iritis

B-Systemic Administration

Most types of corticosteroids penetrate the blood-aqueous barrier. Commonly used drugs are prednisolone, methyl prednisolone and dexamethasone.

Indications: -

1-Interstitual keratitis         

2-Anterior and posterior uveitis   

XII-ANTIHISTAMINES

Histamine antagonists are used to prevent immediate hypersensitivity reaction by preventing histamine formation within the mast cells, preventing its release from the mast cells, competing with it at the site of action and blocking its effect on the receptor cells (chlorpheniramine maleate or Avil®).

XIII-DRUGS USED FOR TREATMENT OF GLAUCOMA

1-CARBONIC ANHYDRASE INHIBITORS

Carbonic anhydrase is an enzyme presented in the ciliary body and is responsible for aqueous production. Its inhibition by carbonic anhydrase inhibitors reduces aqueous humour production and IOP.

1-Acetazolamide (Diamox) 10-20 mg/kg b.w.           

2-Methazol amide (Neptazane) 5 mg/kg b.w.

3-Ethoxzolamide (Ehamide) 5 mg/kg b.w.                 

2-OSMOTIC DIURETICS

Osmotic diuretics are used frequently in veterinary ophthalmology to reduce intraocular pressure. The osmotic agents act by increasing the osmotic concentration of blood, thus drawing fluid from the eye (aqueous and vitreous) directly into the blood stream.

Indications: -

1-Acute glaucoma                

2-Prior to intraocular surgery

3-Traumatic proptosis of the globe to reduce swollen tissues in order to reposition the globe back into the orbit

4-Clearing of corneal edema (when the drug is applied topically)

A-Mannitol

It is a vegetable sugar, penetrates the eye poorly, not metabolized and rapidly excreted by the kidney. Mannitol is administered intravenously in a dose of 1-5 ml/kg b.w. 20% solution in small animals. It causes rapid decrease in intraocular pressure within one hour.

B-Glycerol

It is administered orally in small animals in a dose of 1-2 ml/kg. Glycerol is effective in lowering intraocular pressure. It penetrates the eye poorly and remains extracellular.

C-Urea

It is administered intravenously in a dose of 1-2 gram/kg b.w. 30% solution. Urea is markedly lower intraocular pressure. It penetrates eye readily, not metabolized, and rapidly excreted in urine. Extravascular injection of urea causes sloughing of tissues and phlebitis. It is rarely used since mannitol and glycerol are available.

XIV-VITAMINS

Various vitamins have been advocated for their supposed therapeutic efficacy in the treatment of ocular disorders of animals. In the absence of a specific vitamin, there is little to be gained from such local therapy.

1-VITAMIN A

It plays an important role in the physiology of vision. Vitamin A deficiency causes deterioration of the retina specially rods. Fortunately, they can regenerate with 2-4 months of vitamin A administration. Also it is essential for the normal life of the epithelial cells. In absence of this vitamin the epithelial cells degenerate and atrophy and the basal cells proliferate resulting in keratinization and keratomalacia.

2-VITAMIN C

It is essential for proper maintenance of intercellular cement substances, and its deficiency causes failure of the endothelial cells of the capillaries to produce cement substance resulting in capillary hemorrhage.

3-RIBOFLAVIN (Vit. B)

Vit. B deficiency is characterized by superficial vascularization and ulceration of the cornea.

XV-ENZYMES

Enzymes preparations are rarely used in veterinary ophthalmology.

1-FIBRINOLYSIN

This enzyme is used to remove clotted blood from the anterior chamber in traumatic hyphema. Most of such clots are resorbed spontaneously in 7-10 days. This enzyme acts on fresh clots and should be considered for use in extensive hemorrhage.

2-ALPHA CHYMOTRYPSIN

Trypsin is useful for absorption of intraocular debris in cases of hypopyon. Alpha chymotrypsin is a proteolytic enzyme used for removal of the lens by intra-capsular extraction in cases of cataract. It is used in human but may be of little value in animals as the zonules are considerably more resistant to enzymatic digestion.

XVI-OPHTHALMIC STAINS

Ophthalmic stains are used commonly as diagnostic aids in diseases of anterior and posterior segment of the eye and nasolacrimal system.

1-FLUORESCEIN DYES

Fluorescein is available as solution of 0.5-2.0%. Filter paper stripe impregnated with fluorescein may be placed in the conjunctival sac until moistened by tears. It is readily soluble in water produces a bright green fluorescent color.

Uses: -

1-It acts as an indicator dye for corneal epithelial defects. When the epithelium disrupted, fluorescein rapidly penetrates the corneal stroma, resulting in an intense green fluorescence.

2-It is used for detection of the patency of the nasolacrimal duct. The head may be lowered to aid drainage of tears through the excretory part of the lacrimal system. Within 1-5 minutes, the fluorescein usually appears at the external naries, indicating patency of the NLD.

2-ROSE BENGAL

It stains devitalized corneal and conjunctival cells and their nuclei as well as mucous

XVII-ARTIFICIAL TEARS

In general, aqueous solutions as normal saline are unsuitable for tear replacement because these hydrophilic solutions do not adhere to the lipophilic corneal epithelium. Viscous agents, bind the solution to the epithelium. They are indicated in cases of keratoconjunctivitis sicca, exposure keratitis and as cushioning solution during gonioscopy as well as an ophthalmic vehicle.

1-Methylcellulose 0.5-1.0% solution                                                      

2-Poly vinyl e alcohol 1.4%