Chapter 2
Ocular Therapeutics

Methods of Medicating the Eye (Glaze)

Topical administration (Shell)

Only for cornea, conjunctiva, anterior part of sclera, iris, and ciliary body (mild iritis or iridocyclitis). Topically applied preparations mix readily with the tears and tend to wash away rapidly, therefore concentration of drugs in the tissues you want to treat will depend on the solubility of the drug and the contact time with the cornea and conjunctiva.

Because of the nasolacrimal duct, topically applied drugs may reach the mouth and be absorbed in this manner. This usually is not a problem, but when bitter substances such as atropine are being used, the animal may taste them and begin profuse salivation. This is not harmful because it lasts only a short time, but the client needs to be warned about it.

Drugs which rapidly penetrate mucous membranes will rapidly enter the blood stream through the conjunctiva (e.g., apomorphine placed in the conjunctival sac will result in vomiting within minutes). This can be a serious problem if highly toxic drugs are used indiscriminately. For example, topical cholinesterase inhibitors should not be used for the treatment of glaucoma in cats because they can cause toxicity and death.

Factors affecting penetration of topically applied medication

Corneal epithelium:

The corneal epithelium is relatively impermeable to water soluble compounds and the corneal stroma is relatively impermeable to fat soluble compounds. Thus, drugs that are both fat and water soluble will penetrate the cornea more easily.

Water soluble drugs (most antibiotics, sulfas, and fluorescein) will not penetrate the epithelium, but readily will penetrate the stroma if the epithelium is lost as in the case of an ulcer.

Conjunctiva and sclera:

Penetration through conjunctiva and sclera is an important aspect of this process. Some drugs which poorly will penetrate cornea easily will penetrate conjunctiva/sclera (Ahmed and Patton).

To a certain extent, the higher the drug concentration, the greater the penetration.

Larger molecules generally penetrate more poorly.

The appropriate pH usually has been taken into account in the manufacturing of ophthalmic drugs, and, partly for this reason, you generally should not use non-ophthalmic drugs in the eye.

Types of preparations

Solutions:

These are the least irritating, but have the shortest contact time. They must be given frequently. As with anything placed in the eye, healing of incisions or corneal ulcers is slowed, but not as much as with ointments.

Suspensions:

Similar to solutions. Their disadvantages are that they must be shaken well before use and they should not be used in lavage systems because of the potential for clogging tubes (Apt, et al.).

Ointments:

These tend to last longer than solutions or suspensions, but, for external disease, this usually is not significant. They tend to slow healing more than do solutions or suspensions.

Powders:

These can be quite irritating and should not be used in the eye.

Vehicles of preparations and how they affect contact time

Aqueous:

Readily mixes and flows away with tears. Aqueous solutions may increase the rate of tear evaporation from the eye by washing away the outer oily layer of the tear film.

Methylcellulose:

Provides lubrication and greater contact time than aqueous vehicles.

Hydroxyethylcellulose:

Similar to, but more effective than methylcellulose.

Polyvinyl alcohol:

Similar to methylcellulose.

Polyvinylpyrrolidone:

When used with ethylene glycol polymers, produces a viscous 'artificial mucus' - has the greatest contact time of all the liquids.

Oily bases (lanolin, mineral oil, peanut oil, petrolatum):

In solutions or ointments. Although oil bases compete with the epithelium for fat soluble drugs, this is of little clinical significance. Ointments are preferred immediately after surgery due to reduction in eyelid motility (this allows lubrication and moisturizing of the cornea and conjunctiva until spontaneous blinking recurs).

All oil bases are extremely damaging if given intraocularly, such as during an intraocular procedure. Therefore, they should not be used before or during an intraocular procedure.

Methods of topical ocular therapy

Administration of ointments, solutions or suspensions:

Maximum contact time of a drop is 5-10 minutes - therefore, solutions or suspensions must be given frequently to achieve their full potential.

Maximum contact time of an ointment is about 20 minutes.

Subpalpebral lavage:

This is the most effective method of providing intensive topical treatment. It is used most frequently in horses when topical therapy by other means would be difficult: when continuous or frequent medication is needed, when the eyelids have been sutured together, or when the individual is difficult or dangerous to treat.

One of the simplest ways to achieve this is to use the MILA International Subpalpebral Eye Lavage Kit . This unit comes with its own eyelid needle (trochar), tubing and multiple injection port. This is the general scheme for installing the unit:

1. Sedate the patient
2. Do an auriculopalpebral nerve block
3. Shave the hair from the upper eyelid at the orbital rim and use povidone-iodine soap to cleanse
4. Inject lidocaine or similar local anesthetic subcutaneously in the shaved region
5. Place ophthalmic proparacaine or similar topical anesthetic in the eye
6. 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
7. Insert the lavage tubing through the needle (trochar), going from the inner (conjunctival) to the outer (skin) side
8. Pull the needle (trochar) and tubing through the skin and then remove the needle by pulling it along the tubing and off the end
9. 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
10. 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

This system is much easier to apply and use than others and the total cost at this time is about $20.00 per application.

The article by Schoster provides photographs and more detailed description of another technique and materials required if you choose not to use the MILA system. The pictures may be helpful in visualizing the anatomic landmarks for applying the MILA system.

Cannulation of nasolacrimal duct:

An alternate method to subpalpebral lavage in horses is the use of a catheter in the nasolacrimal duct. Horses can pull these out; however, their ease of insertion may offset this problem.

Simply pass appropriate sized polyethylene tubing through external meatus of nasolacrimal duct up to about level of nasolacrimal sac. Tape is placed on the tubing near the external meatus and the tape sutured to the nose. Enough tubing is used to reach the halter or neck where it is attached; medications can then be applied from a distance.

Subconjunctival injection

Indications and disadvantages

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.

You must be sure of your perceived need for this because once the injection is made, there is no turning back. Many of the medications are quite irritating by this route.

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 ˝ 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.

Comments:

Subconjunctival injection should not be used indiscriminately, but if in your judgment it is the best way to treat a specific patient, it may be indicated. Many patients, however, can be treated with systemic and topical medications as effectively.

Retrobulbar injection

For posterior uveitis, retinitis, and optic neuritis. Although the experienced person can do this fairly innocuously in the dog and the cat, it is safer and just as effective to use systemic medication instead. Main use in veterinary ophthalmology is for optic neuritis where high concentration of corticosteroid is needed. If you believe this is warranted, you should get guidance from a specialist.

Systemic administration

Preferred method of treating diseases of the ocular posterior segment. Most medications are used at the regular recommended dose and rate. However, in certain instances, such as with optic neuritis, much higher than usual doses of corticosteroids are used. Need to keep in mind that there is a blood-ocular barrier similar to that in the brain.

Blood-ocular barrier

The blood-ocular barrier normally keeps most drugs out of the eye. However, inflammation breaks down this barrier allowing drugs and large molecules to penetrate into the eye. As the inflammation subsides, this barrier usually returns.

The blood-ocular barrier is comprised of the following sites:

• Blood-aqueous barrier: The ciliary epithelium and capillaries of the iris.
• Blood-retinal barrier: Non-fenestrated capillaries of the retinal circulation and tight-junctions between retinal epithelial cells preventing passage of large molecules from choriocapillaris into the retina.

Intraocular injection

This generally is used only during intraocular surgery or as a last resort in endophthalmitis. It is recommended you contact a specialist before considering this form of medication as the indications are quite specific and there is great danger of losing the eye if done incorrectly.

Products Available

Topical

Topical anesthetics

Used in the manipulation of cornea, conjunctiva, and nasolacrimal system; also used for minor surgery (e.g., corneal foreign body), tonometry, and gonioscopy; must never be used as treatment because interferes with healing and masks pain. Onset of anesthesia is within seconds after application of two or more drops; 15 or more minutes is average duration.

Tetracaine HCl 1%

May cause transient chemosis in some dogs (Koch and Rubin), but otherwise is excellent.

Various manufacturers (e.g., Alcon).

Proparacaine HCl 0.5%

Should be kept refrigerated and out of light after opening to minimize deterioration.

Alcaine® - Alcon.

Ophthetic® - Allergan.

Topical sulfonamides

Useful against a wide range of bacteria including staphylococci - should be given at least four times a day.

Bleph-10® (10% sulfacetamide) - Allergan - solution.

Topical antibiotics

Should be given at least four times a day.

Chloramphenicol - broad spectrum - good first choice.

Chloromycetin® - Parke-Davis - solution and 1% ointment.

Chloroptic® - Allergan - 0.5% solution.

Chloroptic S.O.P.® - Allergan - 1% ointment - has extended contact time vehicle.

Tetracycline - somewhat broad spectrum - may be especially useful against Chlamydophila and rickettsiae.

Aureomycin® - Lederle - 1% chlortetracycline ointment.

Achromycin® - Lederle - 1% tetracycline ointment.

Terramycin® - Pfizer - oxytetracycline with polymyxin B - ointment.

Gentamicin - good wide spectrum, including Pseudomonas - should reserve use for those cases really needing it; do not use as first choice!

Gentocin® - Schering - solution and ointment - be sure not to confuse with a similarly named ear product.

Optivet® - Burns-Biotec - solution and ointment.

Neomycin and polymyxin B combinations - useful as a first line of defense in most routine infections.

Note well : Neomycin sometimes will produce local sensitization with prolonged use and is the most common cause of topical antibiotic allergy in veterinary medicine.

Neosporin® - Burroughs Wellcome - also contains gramicidin (solution) or bacitracin (ointment).

Ocutricin® - Pharmafair - also contains gramicidin - solution.

Erythromycin - wide range of antimicrobial activity; do not use as first choice.

Ak-Mycin® - Akorn - ointment.

Tobramycin - wide range of antimicrobial activity; do not use as first choice!

Tobrex® - Alcon - solution and ointment.

Topical sulfonamide and steroid combinations

Should be given at least four times a day; use only when anti-inflammatory action is desired in addition to sulfonamide.

Blephamide Liquifilm® (sulfacetamide and prednisolone) - Allergan - suspension.

Blephamide S.O.P.® (sulfacetamide and prednisolone) - Allergan - ointment.

Topical antibiotic and steroid combinations

Should be given at least four times a day; use only when anti-inflammatory action is desired in addition to antibiotic.

Maxitrol® (neomycin, polymyxin B, and 0.1% dexamethasone) - Alcon - suspension and ointment - one of the best combinations.

Gentocin Durafilm® (gentamicin and betamethasone) - Schering - solution; do not use unless you specifically need gentamicin.

Most other combinations are with hydrocortisone which does not have as good anti-inflammatory action as the above.

Topical steroids (Krohne and Vestre)

Anti-inflammatory agents - frequency of use depends on condition; an important factor in steroid therapy is the penetrability of the base: acetate is best, alcohol is next and phosphate has least penetrability. Clinically, however, there usually seems to be little difference in the results regardless of which is used.

Steroids generally are contraindicated in corneal ulceration, especially in horses.

The relative anti-inflammatory strength of various corticosteroids is as follows: desoxycorticosterone 0.0, cortisone 0.8, hydrocortisone 1, prednisolone/prednisone 4, methylprednisolone 5, triamcinolone 5, fludrocortisone 10, betamethasone 25, and dexamethasone 25 (Kreines and Weinberg).

Dexamethasone - one of the best preparations.

Maxidex® - dexamethasone (0.1% suspension) - Alcon - should not use through lavage tubes.

Prednisolone

Pred Forte® (1% as acetate) - Allergan - suspension - should not use through lavage tubes.

1% Econopred Plus® (1% as acetate) - Alcon - suspension - should not use through lavage tubes.

Inflamase Forte® (1% as sodium phosphate) - Cooper Vision - solution - can be used through lavage tubes.

Topical nonsteroidal anti-inflammatory agents

These may be of benefit in situations where you want to reduce prostaglandin synthesis, as an adjunct to conventional anti-inflammatory therapy. The frequency of use generally is one drop three times a day, but this needs to be adjusted on a case by case basis.

Diclofenac sodium - Voltaren® (CIBA Vision) - 0.1% solution.

Flurbiprofen sodium - Ocufen® (Allergan) - 0.03% solution.

Suprofen - Profenal® (Alcon) - solution.

Topical decongestants

Vasoconstrictors used to 'get the red out' - use only for minor irritation or allergy - must first eliminate other causes of ocular hyperemia before prescribing.

Naphazoline

Naphcon Forte® - Alcon - solution.

Albalon® - Allergan - solution.

Phenylephrine

Prefrin Liquifilm® (0.12%) - Allergan - solution.

Artificial tears and ocular lubricants

Artificial tears are used to supplement natural tear production whenever it is below normal, e.g., in keratoconjunctivitis sicca; need to be given frequently. Ocular lubricants, although not a substitute for tears, provide comfort due to lubrication and may be particularly useful prior to extended periods when artificial tears cannot be applied, such as at night before sleep.

Ocular lubricants

These provide lubrication, but not wetting and should not be considered a substitute for artificial tears.

Lacri-Lube S.O.P.® (white petrolatum, mineral oil, and lanolin derivatives) - Allergan - very good lubricant.

Tearfair® (white petrolatum, mineral oil, and lanolin) - Pharmafair - very good lubricant.

Duratears®Naturale (white petrolatum, mineral oil, and lanolin) - Alcon - very good lubricant.

Artificial tears

Liquifilm Forte® (polyvinyl alcohol) - Allergan.

Adsorbotear® (polyvinylpyrrolidone and hydroxyethylcellulose) - Alcon.

Dissolvable inserts

Lacrisert® (hydroxypropyl cellulose) - 5 mg ophthalmic inserts; slowly release the active material; useful for low tear producers (there must be some tear production) in situations when client cannot place artificial tears into eye frequently enough - Merck, Sharp & Dohme.

Miscellaneous treatment for keratoconjunctivitis sicca

Cyclosporine

Optimmune® - 0.2% ointment - Schering-Plough Animal Health; apply small amount to affected eye twice a day.

Although you could compound an ophthalmic preparation yourself, because it now is available commercially, "...supplies of cyclosporin for veterinary ophthalmic use should be obtained from the exclusive sublicensee, Schering-Plough Animal Health, in countries where it is approved and marketed." If this legal constraint does not apply to your situation, the following is the manner in which a 1% or 2% ophthalmic suspension has been compounded in the past at the School of Veterinary Medicine, University of California, Davis:

1. Sandimmune® oral solution of cyclosporine - use 1 ml for a 1% suspension or 2 ml for a 2% suspension.
2. Light mineral oil, Roxane Laboratories (heat sterilized) - need 8 ml.
3. Add the cyclosporine and mineral oil to a 15 ml plastic 'droptainer'. The preparation will have a six week shelf life. It must be shaken well before use. Apply one drop in the affected eye twice a day.

Iridocycloplegics

Will provide pupillary dilatation for ocular exam or prevention of synechiae in the visual axis; iridocycloplegics also relieve iris and ciliary spasm which are painful aspects of keratitis and uveitis; contraindicated in glaucoma.

Tropicamide (Hacker and Farver) - 1% solution - quick onset (10-15 minutes in dogs and cats, 20-25 minutes in horses) and short duration (4-8 hours) - ideal for fundus exams; not suitable for most treatment regimens because it is relatively weak and too short in duration.

Mydriacyl® - Alcon .

Mydriafair® - Pharmafair, Inc.

Atropine - various manufacturers - from 0.5% to 4% concentration (solution in all concentrations, ointment in lower concentrations) - 1% usually is adequate - onset in one-half hour, duration may be days to weeks. Horses often need the higher concentrations for uveitis treatment.

Mydriatics

Will not provide iridocycloplegia; contraindicated in glaucoma.

Phenylephrine - various manufacturers - 10% solution - no iridocycloplegia - useful in providing pupillary dilatation without affecting accommodation, but this generally is not of concern with susceptible nonhuman patients - onset in one-half hour, duration several hours - mainly for use in primates as it does not work well alone in dogs, cats or horses - used to supplement iridocycloplegics in these species under certain circumstances, but still may be of no use in horses (Hacker, et al.).

Hydroxyamphetamine - 1% solution; useful in determining if site of lesion in Horner's syndrome is pre- or post-ganglionic; not used therapeutically.

Paredrine® - Pharmics

Miotics

For pupillary constriction, but not often indicated; most are used in anti-glaucoma therapy and are listed under that heading.

Acetylcholine

Miochol® (acetylcholine) - Smith, Miller, and Patch - solution.

Pilocarpine - various manufacturers and concentrations - solution; also used orally to stimulate lacrimal secretion.

Anticholinesterase agents - various ones - see under anti-glaucoma agents; usually best not to use.

Topical antifungal medications

One federally approved ophthalmic preparation in the USA is natamycin. It is extremely expensive. Non-ophthalmic medications can be used and can be effective depending on the fungus involved (Coad, et al.).

Polyenes

Highly insoluble, most are unstable (cannot heat sterilize) - most are irritating to the eye.

Nystatin - Moderately effective for Candida sp., but usually not effective for others.

Mycostatin® - dermatologic ointment (100,000 units/gram) - Squibb - works well and is easy to use.

Powder - make up 50,000 units/ml suspension in saline - use at least four times a day.

Amphotericin B

Make up 5 mg/ml suspension in 5% dextrose - may not be advisable to use Fungizone® (Squibb) because it contains desoxycholate which can cause corneal ulceration; highly effective against Candida sp. and somewhat effective for some others.

Natamycin (pimaricin)  5% suspension available from Alcon - called Natacyn®; effective against Aspergillus, Fusarium and Cephalosporium; good first choice prior to culture results, but expensive.

Imidizoles

Clotrimazole

Experimental - in the 1980's, was available from Dr. Dan Jones, Department of Ophthalmology, Baylor College of Medicine, Texas Medical Center, Houston, Texas 77025; do not know if this is currently the case.

Can be used as 1% in oil or ointment; highly effective against Aspergillus, Alternaria, Candida, and Mucor; ineffective against most Fusarium sp.

Thiobendazole

Use 4% suspension in water; some effectiveness against Fusarium sp., Penicillium, Phiolophera, and Cladosporium.

Miconazole

Monistat i.v.® - 10 mg/ml intravenous solution - Taylor Pharmacal Co.

Pyrimidines

Flucytosine

Use 1.5% aqueous solution; effective against Candida and Cryptococcus neoformans.

Topical antiviral medications

These have been developed for use in human herpetic keratitis - do have some efficacy in proven viral keratitis in domestic animals.

Various treatment regimens - generally need to apply frequently to be effective: one drop every minute for five minutes repeated every four hours, or one drop every hour (every other hour at night).

Idoxuridine

Stoxil® - Smith, Kline & French - solution or ointment.

Herplex Liquifilm® - Allergan - solution.

Herplex S.O.P.® - Allergan - ointment.

Vidarabine

Vira-A® - Parke-Davis - ointment - less problems with toxicity and allergies than with idoxuridine; discontinued by manufacturer as of August 2001.

Trifluridine

Viroptic® - Burroughs Wellcome - solution - may be least toxic and most effective of all topical antiviral medications.

Topical hyperosmotic medications

Used to reduce corneal edema - generally not very effective and may be irritating.

Sodium chloride

Adsorbonac® - Alcon - 2-5% solution - dose 1-2 drops 2-3 times a day.

Muro 128® - Bausch & Lomb Pharmaceuticals, Inc. - 5% ointment.

Topical anticollagenase medications

For use in cases of corneal ulcers where collagenolytic action is suspected. There is controversy about the appropriateness of using this mode of therapy. Whereas some experimentally induced collagenolytic corneal disease has responded favorably to collagenase inhibition, there is little evidence of efficacy in clinical cases. The artificial agents can be very irritating to the patient and contribute adversely to the progress of a particular situation. At the time of writing this version of these notes, I cannot recommend the use of artificial anticollagenase agents.

Acetylcysteine - Mucomyst® - Mead Johnson - 10% solution - manufactured for respiratory use for its mucolytic action, but widely is used in ophthalmology although not approved by Food and Drug Administration; according to Costa and Slatter, it is not necessary to refrigerate Mucomyst® and it should continue to be effective up to two months.

Chelating agents - because collagenase requires calcium for its action, any chelating drug which binds calcium will provide temporary relief; ethylenediaminetetraacetic acid is most popular; needs frequent application.

Serum - due to alpha-2-macroglobulin - acts as chelator.

Cauterizing agents for corneal ulcers

Use only when healing does not occur by other means.

2% tincture of iodine; safe; best one to use.

Subconjunctival administration

Most systemic preparations can be used subconjunctivally, but many are extremely irritating; volume should not exceed ˝ ml in cat or dog, 1 ml in large animals.

Subconjunctival steroids

Triamcinolone

Vetalog® - Squibb - 6 mg/ml or higher concentration - very good, well-tolerated.

Subconjunctival mydriatics or iridocycloplegics

Atropine - use the 0.4 mg/ml concentration of injectable form.

Subconjunctival antibiotics

Various systemic preparations, but generally best not to use; consult a specialist before considering this form of therapy.

Retrobulbar administration

Can use same products as with subconjunctival, but generally best not to use; consult a specialist before considering this form of therapy.

Systemic administration

Systemic antibiotics

Use broad spectrum; e.g., chloramphenicol or ampicillin.

Systemic steroids

Dexamethasone, prednisone and prednisolone are good.

Anti-glaucoma agents

The most important aspect of glaucoma therapy is early and accurate diagnosis - you may not be able to effectively treat glaucoma unless the reason for increased intraocular pressure is known; generally, glaucoma in domestic animals does not respond well to medical therapy.

Carbonic anhydrase inhibitors

These reduce aqueous production - maximum benefit is 50%, usually less.

Dichlorphenamide - Daranide® - Merck, Sharp & Dohme - 50 mg tablets - dose 4.4 - 8.8 mg/kg body weight twice or three times a day.

Other carbonic anhydrase inhibitors may produce more harmful side effects.

When using carbonic anhydrase inhibitors on a chronic basis, be sure patient is receiving adequate nourishment because potassium can become depleted.

Hyperosmotic agents

For quick reduction of intraocular pressure - use as immediate therapy while waiting for other treatments to take effect or prior to intraocular surgery (Dugan, et al.; Lorimer, et al.); must have intact blood-ocular barrier for osmotic agents to have effect.

Mannitol - used intravenously - dose 1-2 gm/kg body weight given over 5-10 minutes.

Glycerol (50%) - orally administered - dose 2 ˝ cc/kg body weight initially, then the same dose divided into three equal amounts three times a day for maintenance.

Miotics

Useful in open angle glaucoma which is relatively rare in domestic animals; miotics improve aqueous outflow facility.

Pilocarpine - various manufacturers and concentrations, all solutions - 1% most commonly used - dose 2 drops 3-4 times a day; also comes as a continuous delivery membrane called Ocusert® by Alza Pharmaceuticals.

Continued topical use of pilocarpine (especially greater than 1%) may cause tissue sensitization in some patients (manifested by redness and pain).

Cholinesterase inhibitors

These include demecarium bromide and echothiophate iodide and probably offer no advantage over pilocarpine. They can cause considerably more discomfort for the patient and are contraindicated in cats. I do not recommend they be used if they cause discomfort for a particular patient.

Epinephrine preparations

Useful in open angle glaucoma; often used in conjunction with miotics; causes decrease in aqueous production and increase in outflow facility; when used chronically, may cause brown-black deposits in eyelids, conjunctiva and cornea.

Dipivefrin HCl - Propine® - Allergan - solution - dose one drop twice a day. This is a prodrug; it breaks down into epinephrine after absorption.

Diagnostic agents

Fluorescein strips

Used for delineating regions of corneal ulceration; ultraviolet or cobalt blue light enhances visualization.

Ful-Glo® - Sola/Barnes-Hind.

Fluor-I-Strip® - Wyeth-Ayerst.

Standardized sterile strips for tear production evaluation

Schirmer Tear Test - Schering-Plough Animal Health; these strips have a color bar tear front indicator and a millimeter scale on each strip.

Schirmer Tear Test - Smith, Miller, and Patch.

Rose bengal dye

Vital dye for dead or degenerating cells and mucus; use only the prepackaged sterile strips. Of limited use to the general practitioner.

Fluorescein solution for angiography

Used intravenously to do angiography of retinal and choroidal vasculature; 10% solution. Of limited use to the general practitioner.

Ocular Toxicity of Systemic Medications

You should be aware of possible side-effects of various medications on the visual system. The following is a partial list of drugs that have had associated ocular problems. Most of these have been observed in human beings and may not be applicable to nonhuman animals unless noted. Some are species-specific whereas others have applicability to any animal.

Anesthetics and tranquilizers

Barbiturates

Ptosis; extraocular muscle palsies; nystagmus; allergic conjunctivitis; blindness (usually temporary, of cortical or peripheral origin).

Chlorpromazine

Temporary toxic amblyopia; retinal degeneration.

Anti-epileptic drugs

Diphenylhydantoin

Allergic dermatitis and conjunctivitis; nystagmus; ptosis.

Primidone

Edema of eyelids and orbit.

Anti-inflammatory or analgesic drugs

Phenylbutazone

Conjunctivitis; retinal bleeding; toxic amblyopia.

Salicylates

Toxic amblyopia; cortical blindness; mydriasis; conjunctivitis (allergic); nystagmus; ocular hypotony.

Steroids

Potentiation of viral, bacterial, and fungal ocular infections; causes adrenal suppression when used topically, but generally not a clinical problem (Roberts, et al.); in human beings, posterior subcapsular cataract and glaucoma have been documented.

Antimicrobial drugs

Bacitracin, neomycin, polymyxin ophthalmic preparations

Anaphylaxis in cats (Plunkett, Signe J.).

Chloramphenicol

Toxic amblyopia; mydriasis in dogs and cats.

Enrofloxacin

Retinal degeneration in cats (Gelatt, et al.).

Streptomycin

Toxic amblyopia.

Sulfonamides

Ocular palsies; iritis; retinal edema and bleeding; toxic amblyopia; keratoconjunctivitis sicca; allergic reactions (Giger, et al.).

Belladonna alkaloids

Atropine (and similar drugs)

Risk of angle-closure glaucoma; diminished lacrimal secretion.

Cardiovascular drugs

Digitalis

Cortical blindness; lowering of intraocular pressure; ocular palsies; conjunctivitis.

Diuretics

Chlorthiazide

Retinal edema.

Female sex hormones

Papilledema; nystagmus; optic neuritis; retinal perivasculitis; cyclitis; cycloplegia; mydriasis.

Vitamins

Vitamin A

Loss of eyebrows and eyelashes; ocular palsies; nystagmus; exophthalmos; papilledema; retinal bleeding.

Vitamin D (often plus calcium)

Band-shaped corneal degeneration with calcium deposits in conjunctiva and cornea.

Miscellaneous

Phenazopyridine

Keratoconjunctivitis sicca in dogs.

Succinylcholine

Contracts extraocular muscles, raising intraocular pressure (of importance when doing intraocular surgery).

Footnotes:

MILA contact information: As of 1997, MILA's toll free voice phone is 888.645.2468; another voice phone is 606.371.6452. Their fax is 606.371.6499.

Legal status of cyclosporine use for keratoconjunctivitis sicca: Letter dated 12 May 1997, from Judy C. Butler, The University of Georgia Research Foundation, Inc., the latter which holds the patent on the use of cyclosporine for stimulating tear production.

Corneal ulceration and amphotericine B: Dr. Jill Beech at the University of Pennsylvania has been routinely using Fungizone® with no apparent problems. She dilutes with water initially, then finally with 5% dextrose.