COMMONLY USED EYE MEDICATIONS

The following is intended to serve as a concise formulary of commonly used ophthalmic drugs. Standard pharmacology and physiology texts should be consulted for more detailed information.

TOPICAL ANESTHETICS

Topical anesthetics are useful for several diagnostic and therapeutic procedures, including tonometry, removal of foreign bodies or sutures, gonioscopy, conjunctival scraping, and minor surgical operations on the cornea and conjunctiva. One or two instillations are usually sufficient, but the dosage may be repeated during the procedure.

Proparacaine, tetracaine, and benoxinate are the most commonly used topical anesthetics. For practical purposes, they can be said to have equivalent anesthetic potency.

Cocaine 1-4% solution is also used for topical anesthesia.

Note: Topical anesthetics should never be prescribed for home use, since prolonged application may cause corneal complications and mask serious ocular disease.

Proparacaine Hydrochloride (Ophthaine, Others)

• Preparation: Solution, 0.5%. A combined preparation of proparacaine and fluorescein is available as Fluoracaine.
• Dosage: 1 drop and repeat as necessary.
• Onset and duration of action: Anesthesia begins within 20 seconds and lasts 10-15 minutes.
• Comment: Least irritating of the topical anesthetics.

Tetracaine Hydrochloride (Pontocaine)

• Preparations: Solution, 0.5%, and ointment, 0.5%.
• Dosage: 1 drop and repeat as necessary.
• Onset and duration of action: Anesthesia occurs within 1 minute and lasts for 15-20 minutes.
• Comment: Stings considerably on instillation.

Benoxinate Hydrochloride

• Preparation (as Fluress): Solution, 0.4%.
• Dosage: 1 drop and repeat as necessary.
• Onset and duration of action: Anesthesia begins within 1 or 2 minutes and lasts for 10-15 minutes.
• Comment: Benoxinate 0.4% and fluorescein 0.25% (Fluress) may be used prior to applanation tonometry.

LOCAL ANESTHETICS FOR INJECTION

Lidocaine, procaine, and mepivacaine are commonly used local anesthetics for eye surgery. Longer-acting agents such as bupivacaine and etidocaine are often mixed with other local anesthetics to prolong the duration of effect. Local anesthetics are extremely safe when used with discretion, but the physician must be aware of the potential systemic toxic action when rapid absorption occurs from the site of the injection, with excessive dosage, or following inadvertent intravascular injection.

The addition of hyaluronidase encourages spreading of the anesthetic and shortens the onset to as little as 1 minute. For these reasons, hyaluronidase is commonly used in retrobulbar and peribulbar injections prior to cataract extraction. Injectable anesthetics are used by ophthalmologists most commonly in older patients, who may be susceptible to cardiac arrhythmias; therefore, l-epinephrine should not be used in concentrations greater than 1:200,000.

Lidocaine Hydrochloride (Xylocaine)

Owing to its rapid onset and longer action (1-2 hours), lidocaine has become the most commonly used local anesthetic. It is approximately twice as potent as procaine. Up to 30 mL of 1% solution, without epinephrine, may be used safely. In cataract surgery, 15-20 mL is usually more than adequate. The maximum safe dose is 4.5 mg/kg without epinephrine and 7 mg/kg with epinephrine. Recently, intracameral lidocaine in a 1% solution without preservatives has been employed for anesthesia in cataract surgery.

Procaine Hydrochloride (Novocaine)

• Preparations: Solution, 1%, 2%, and 10%.
• Dosage: Approximately 50 mL of a 1% solution can be injected without causing systemic effects. The maximum safe dose is 10 mg/kg.
• Duration of action: 45-60 minutes.

Mepivacaine Hydrochloride (Carbocaine, Others)

• Preparations: Solution, 1%, 1.5%, 2%, and 3%.
• Dosage: Infiltration and nerve block, up to 20 mL of 1% or 2% solution.
• Duration of action: Approximately 2 hours.
• Comment: Carbocaine is similar to lidocaine in potency. It is usually used in patients who are allergic to lidocaine. The maximum safe dose is 7 mg/kg.

Bupivacaine Hydrochloride (Marcaine, Sensorcaine)

• Preparations: Solution, 0.25%, 0.5%, and 0.75%.
• Dosage: The 0.75% solution has been used most frequently in ophthalmology. The maximum safe dose in an adult is 250 mg with epinephrine and 200 mg without epinephrine. Bupivacaine is frequently mixed with an equal amount of lidocaine.
• Onset and duration of action: The onset of action is slower than that of lidocaine, but it persists much longer (up to 6-10 hours).

Etidocaine Hydrochloride (Duranest)

• Preparations: Solution, 1% and 1.5%.
• Dosage: The maximum safe dose of etidocaine is 4 mg/kg without epinephrine and 5.5 mg/kg with epinephrine. This agent is frequently mixed with lidocaine for local anesthesia in ophthalmic surgery.
• Onset and duration of action: The onset of action is slower than that of lidocaine but more rapid than that of bupivacaine. The duration of action is approximately twice as long as that of lidocaine (4-8 hours).

MYDRIATICS & CYCLOPLEGICS

Mydriatics and cycloplegics both dilate the pupil. In addition, cycloplegics cause paralysis of accommodation (patient unable to see near objects, eg, printed words). They are commonly used drugs in ophthalmology, singly and in combination. Their prime uses are (1) for dilating the pupils to facilitate ophthalmoscopy; (2) for paralyzing the muscles of accommodation, particularly in young patients, as an aid in refraction; and (3) for dilating the pupil and paralyzing the muscles of accommodation in uveitis to prevent synechia formation and relieve pain and photophobia. Since mydriatics and cycloplegics both dilate the pupil, they should be used with extreme caution in eyes with narrow anterior chamber angles since either a mydriatic or a cycloplegic can cause angle-closure glaucoma in such eyes.

1. MYDRIATICS (Sympathomimetics)

Phenylephrine is a mydriatic with no cycloplegic effect.

Phenylephrine Hydrochloride (Neo-Synephrine, Others)

• Preparations: Solution, 0.12%, 2.5%, and 10%.
• Dosage: 1 drop and repeat in 5-10 minutes.
• Onset and duration of action: The effect usually occurs within 30 minutes after instillation and lasts 2-3 hours.
• Comment: Phenylephrine is used both singly and with cycloplegics to facilitate ophthalmoscopy, in treatment of uveitis, and to dilate the pupil prior to cataract surgery. It is used almost to the exclusion of all other mydriatics. If a patient is allergic to phenylephrine, hydroxyamphetamine hydrobromide (Paredrine) may be substituted. The 10% solution should not be used in newborn infants, in cardiac patients, or in patients receiving reserpine, guanethidine, or tricyclic antidepressants, because of increased susceptibility to the vasopressor effects.

2. CYCLOPLEGICS (Parasympatholytics)

Atropine Sulfate

• Preparations: Solution, 0.5-3%; ointment, 0.5% and 1%.
• Dosage: For refraction in children, instill 1 drop of 0.25-0.5% solution in each eye twice a day for 1 or 2 days before the examination and then 1 hour before the examination; ointment, ¼-inch ribbon twice a day for 2 days prior to examination.
• Onset and duration of action: The onset of action is within 30-40 minutes. A maximum effect is reached in about 2 hours. The effect lasts for up to 2 weeks in a normal eye, but in the presence of acute inflammation the drug must be instilled two or three times daily to maintain its effect.
• Toxicity: Atropine drops must be used with caution to avoid toxic reactions resulting from systemic absorption. Restlessness and excited behavior with dryness and flushing of the skin of the face, dry mouth, fever, inhibition of sweating, and tachycardia are prominent toxic symptoms, particularly in young children.
• Comment: Atropine is an effective and long-acting cycloplegic. In addition to its use for cycloplegia in children, atropine is applied topically two or three times daily in the treatment of iritis. It is also used to maintain a dilated pupil after intraocular surgical procedures.

Scopolamine Hydrobromide

• Preparation: Solution, 0.25%.
• Dosage: 1 drop two or three times daily.
• Onset and duration of action: Cycloplegia occurs in about 40 minutes and lasts for 3-5 days when scopolamine is used as an aid to refraction in normal eyes. The duration of action is much shorter in inflamed eyes.
• Toxicity: Scopolamine occasionally causes dizziness and disorientation, mainly in older people.
• Comment: Scopolamine is an effective cycloplegic. It is used in the treatment of uveitis, in refraction of children, and postoperatively.

Homatropine Hydrobromide

• Preparations: Solution, 2% and 5%.
• Dosage: For refraction, 1 drop in each eye and repeat two or three times at intervals of 10-15 minutes.
• Onset and duration of action: Maximal cycloplegic effect lasts for about 3 hours, but complete recovery time is about 36-48 hours. In certain cases, the shorter action is an advantage over scopolamine and atropine.
• Toxicity: Sensitivity and side effects associated with the topical instillation of homatropine are rare.

Cyclopentolate Hydrochloride (Cyclogyl, Others)

• Preparations: Solution, 0.5%, 1%, and 2%.
• Dosage: For refraction, 1 drop in each eye and repeat after 10 minutes.
• Onset and duration of action: The onset of dilatation and cycloplegia is within 30-60 minutes. The duration of action is less than 24 hours.
• Comment: Cyclopentolate is more popular than homatropine and scopolamine in refraction because of its shorter duration of action. Occasionally, neurotoxicity may occur, manifested by incoherence, visual hallucinations, slurred speech, and ataxia. These reactions are more common in children.

Tropicamide (Mydriacyl, Others)

• Preparations: Solution, 0.5% and 1%; 0.25% with 1% hydroxamphetamine hydrobromide (Paremyd).
• Dosage: 1 drop of 1% solution two or three times at 5-minute intervals.
• Onset and duration of action: The time required to reach the maximum cycloplegic effect is usually 20-25 minutes, and the duration of this effect is only 15-20 minutes; therefore, the timing of the examination after instilling tropicamide is important. Complete recovery requires 5-6 hours.
• Comment: Tropicamide is an effective mydriatic with weak cycloplegic action and is therefore most useful for ophthalmoscopy.

Cyclopentolate Hydrochloride-Phenylephrine Hydrochloride (Cyclomydril)

• Preparation: Solution, 0.2% cyclopentolate hydrochloride and 1% phenylephrine hydrochloride.
• Dosage: 1 drop every 5-10 minutes for two or three doses. Pressure should be applied over the nasolacrimal sac after drop instillation to minimize systemic absorption.
• Onset and duration of action: Mydriasis and some cycloplegia occur within the first 3-6 minutes. The duration of action is usually less than 24 hours. This drug combination is of particular value for pupillary dilation in examination of premature and small infants.

DRUGS USED IN THE TREATMENT OF GLAUCOMA

The concentration used and the frequency of instillation should be individualized on the basis of tonometric measurements. Use the smallest dosage that effectively controls the intraocular pressure and prevents optic nerve damage.

1. DIRECT-ACTING CHOLINERGIC (PARASYMPATHOMIMETIC) DRUGS

Pilocarpine Hydrochloride & Nitrate

• Preparations: Solution, 0.25%, 0.5-6%, 8%, and 10%; gel, 4%. Also available in a sustained-release system (Ocusert).
• Dosage: 1 drop up to six times a day; a ½-inch strip of gel in lower conjunctival cul-de-sac at bedtime.
• Comment: Pilocarpine was introduced in 1876 and is still a commonly used antiglaucoma drug.

Carbachol, Topical

• Preparations: Solution, 0.75%, 1.5%, 2.25%, and 3%.
• Dosage: 1 drop in each eye three or four times a day.
• Comment: Carbachol is poorly absorbed through the cornea and usually is used if pilocarpine is ineffective. Its duration of action is 4-6 hours. If benzalkonium chloride is used as the vehicle, the penetration of carbachol is significantly increased.

2. INDIRECT-ACTING REVERSIBLE ANTICHOLINESTERASE DRUGS

Physostigmine Salicylate & Sulfate (Eserine)

• Preparations: Solution, 0.25%, and ointment, 0.25%.
• Dosage: 1 drop three or four times a day or ¼-inch strip of ointment once or twice a day.
• Comment: A high incidence of allergic reactions has limited the use of this old and seldom used antiglaucoma drug. It can be combined in the same solution with pilocarpine.

3. INDIRECT-ACTING IRREVERSIBLE ANTICHOLINESTERASE DRUGS

These drugs are strong and long-lasting and are used when other antiglaucoma medications fail to control the intraocular pressure. They are employed less frequently than in the past. The miosis produced is extreme; ciliary spasm and myopia are common. Local irritation is common, and phospholine iodide is believed to be cataractogenic in some patients. Pupillary block may occur. With the development of newer antiglaucoma medications, these agents are used much less commonly than in the past.

Echothiophate Iodide (Phospholine Iodide)

• Preparations: Solution, 0.03%, 0.06%, 0.125%, and 0.25%
• Dosage: 1 drop once or twice daily or less often, depending upon the response.
• Comment: Echothiophate iodide is a long-acting drug similar to isoflurophate that has the advantages of being water-soluble and causing less local irritation. Systemic toxicity may occur in the form of cholinergic stimulation, including salivation, nausea, vomiting, and diarrhea. Ocular side effects include cataract formation, spasm of accommodation, and iris cyst formation.

Demecarium Bromide (Humorsol)

• Preparations: Solution, 0.125% and 0.25%.
• Dosage: 1 drop once or twice a day.
• Comment: Systemic toxicity similar to that associated with echothiophate iodide may occur.

4. ADRENERGIC (SYMPATHOMIMETIC) DRUGS

In the treatment of glaucoma, epinephrine has the advantages of long duration of action (12-72 hours) and no miosis, which is especially important in patients with incipient cataracts (effect on vision not accentuated). At least 25% of patients develop local allergies; others complain of headache and heart palpitation (less common with dipivefrin).

Epinephrine acts by increasing outflow of aqueous humor.

Some of the preparations available for use in open-angle glaucoma are listed below. The dosage is the same for all, ie, 1 drop once or twice daily:

• Epinephrine borate (Eppy/N), 0.5%, 1%, and 2%.
• Epinephrine hydrochloride (Epifrin, Glaucon), 0.25%, 0.5%, 1%, and 2%.
• Dipivefrin hydrochloride (Propine), 0.1%.

5. BETA-ADRENERGIC BLOCKING DRUGS

Timolol Maleate (Timoptic; Timoptic XE, Betimol)

• Preparations: Solution, 0.25% and 0.5%; gel, 0.25% and 0.5%.
• Dosage: 1 drop of 0.25% or 0.5% in each eye once or twice daily if needed. One drop of gel once daily.
• Comment: Timolol maleate is a nonselective beta-adrenergic blocking agent applied topically for treatment of open-angle glaucoma, aphakic glaucoma, and some types of secondary glaucoma. A single application can lower the intraocular pressure for 12-24 hours. Timolol has been found to be effective in some patients with severe glaucoma inadequately controlled by maximum tolerated antiglaucoma therapy with other drugs. The drug does not affect pupillary size or visual acuity. Although timolol is usually well tolerated, it should be prescribed cautiously for patients with known contraindications to systemic use of beta-adrenergic blocking drugs (eg, asthma, heart failure). (See discussion of side effects, below.)

Betaxolol Hydrochloride (Betoptic; Betoptic S)

• Preparations: Solution, 0.25% (Betoptic S) and 0.5%.
• Dosage: 1 drop once or twice daily.
• Comment: Betaxolol has comparable efficacy to timolol in the treatment of glaucoma. Its relative ₁ receptor selectivity reduces the risk of pulmonary side effects, particularly in patients with reactive airway disease.

Levobunolol Hydrochloride (Betagan)

• Preparations: Solution, 0.25% and 0.5%.
• Dosage: 1 drop once or twice daily.
• Comment: Levobunolol is a nonselective ₁ and ₂ blocker. It has effects comparable to those of timolol in the treatment of glaucoma.

Metipranolol Hydrochloride (OptiPranolol)

• Preparation: Solution, 0.3%.
• Dosage: 1 drop once or twice daily.
• Comment: Metipranolol is a nonselective ₁ and ₂ blocker with ocular effects similar to those of timolol.

Carteolol Hydrochloride (Ocupress)

• Preparation: Solution, 1%.
• Dosage: One drop once or twice daily.
• Comment: Carteolol is a nonselective beta-blocker with pharmacologic effects similar to those of other topical beta-blockers used for the treatment of glaucoma.

6. ALPHA-ADRENERGIC AGONISTS

Apraclonidine Hydrochloride (Iopidine)

• Preparation: Solution, 0.5% and 1%.
• Dosage: 1 drop of 1% solution before anterior segment laser treatment and a second drop upon completion of the procedure. One drop of 0.5% solution two or three times a day as short-term adjunctive treatment in glaucoma patients receiving other medications.
• Comment: Apraclonidine hydrochloride is a selective -adrenergic agonist that has been applied topically for prevention and management of intraocular pressure elevations after anterior segment laser procedures. It is also used as short-term adjunctive therapy in patients on maximally tolerated medical therapy who need further reduction of intraocular pressure. Apraclonidine lowers intraocular pressure by decreasing aqueous humor formation, the exact mechanism of which is not clearly understood. It may also improve aqueous outflow. Unlike clonidine, apraclonidine does not appear to penetrate blood-tissue barriers easily and produces few side effects. The reported systemic side effects include occasional decreases in diastolic blood pressure, bradycardia, and central nervous system symptoms of insomnia, irritability, and decreased libido. Ocular side effects include conjunctival blanching, upper lid elevation, mydriasis, and burning.

Brimonidine Tartrate (Alphagan)

Brimonidine is an adrenergic agonist that lowers intraocular pressure by decreasing aqueous production and perhaps also by increasing outflow through the uveoscleral pathway. It has only minimal effect on heart rate and blood pressure.

• Preparation: Solution, 0.2%.
• Dosage: One drop two or three times daily. May be used as monotherapy or in combination with other glaucoma medications. Frequently used as a replacement drug in patients unable to tolerate beta-blockers.
• Toxicity: Dry mouth, stinging, and redness are the most common side reactions.

7. CARBONIC ANHYDRASE INHIBITORS

Inhibition of carbonic anhydrase in the ciliary body reduces the secretion of aqueous. The oral administration of carbonic anhydrase inhibitors is especially useful in reducing the intraocular pressure in selected cases of open-angle glaucoma and can be used with some effect in angle-closure glaucoma.

The carbonic anhydrase inhibitors in use are sulfonamide derivatives. Oral administration produces the maximum effect in approximately 2 hours; intravenous administration, in 20 minutes. The duration of maximal effect is 4-6 hours following oral administration.

The carbonic anhydrase inhibitors are used in patients whose intraocular pressure cannot be controlled with eye drops. They are valuable for this purpose but have many undesirable side effects, including potassium depletion, gastric distress, diarrhea, exfoliative dermatitis, renal stone formation, shortness of breath, fatigue, acidosis, and tingling of the extremities. Since the advent of timolol, topical carbonic anhydrase inhibitors, other newer glaucoma medications, and laser therapy, systemic carbonic anhydrase inhibitors are being used less frequently.

Acetazolamide (Diamox)

• Preparations and dosages:
• Oral: Tablets, 125 mg and 250 mg; give 125-250 mg two to four times a day (dosage not to exceed 1 g in 24 hours). Sustained-release capsules, 500 mg; give 1 capsule once or twice a day.
• Parenteral: May give 500-mg ampules intramuscularly or intravenously for short periods in patients who cannot tolerate the drug orally.

Methazolamide (Neptazane)

• Preparation: Tablets, 25 and 50 mg.
• Dosage: 50-100 mg two or three times daily (total not to exceed 600 mg/d).

Dichlorphenamide (Daranide)

• Preparation: Tablets, 50 mg.
• Dosage: Give a priming dose of 100-200 mg followed by 100 mg every 12 hours until the desired response is obtained. The usual maintenance dosage for glaucoma is 25-50 mg three or four times daily. The total daily dosage should not exceed 300 mg daily.

Dorzolamide Hydrochloride (Trusopt)

Dorzolamide is a topical carbonic anhydrase inhibitor. It is a sulfonamide product with sufficient corneal penetration to reach the secretory epithelium of the ciliary body and reduce intraocular pressure by decreasing aqueous secretion.

• Preparation: Solution, 2%.
• Dosage: 1 drop two to four times daily. May be used as monotherapy but most frequently used in combination with other glaucoma medications.
• Toxicity: Local reactions include burning and stinging, superficial punctate keratopathy, and allergic reactions of the conjunctiva. Bitter after-taste is common. Systemic side reactions associated with oral carbonic anhydrase agents are rare.

8. PROSTAGLANDIN ANALOGS

Latanoprost (Xalatan)

Latanoprost is a selective prostanoid FP receptor agonist that appears to reduce intraocular pressure by increasing outflow of aqueous humor, mainly via the uveoscleral pathway. This agent may be used alone or in combination with other glaucoma medications.

• Preparation: Solution, 0.005%.
• Dosage: 1 drop once daily in the evening.
• Onset and duration of action: Reduction of intraocular pressure occurs in 3-4 hours, and the maximum effect is reached in 8-12 hours.
• Toxicity: Increased brown pigmentation of the iris may occur in some patients. Additionally, conjunctival hyperemia, punctate epithelial keratopathy, and foreign body sensation may occur in a small number of patients.

9. OSMOTIC AGENTS

Hyperosmotic agents such as urea, mannitol, and glycerin are used to reduce intraocular pressure by making the plasma hypertonic to aqueous humor. These agents are generally used in the management of acute (angle-closure) glaucoma and occasionally in pre- or postoperative surgery when reduction of intraocular pressure is indicated. The dosage for all is approximately 1.5 g/kg.

Glycerin (Osmoglyn)

• Preparations and dosage: Glycerin is usually given orally as 50% solution with water, orange juice, or flavored normal saline solution over ice (1 mL of glycerin weighs 1.25 g). Dose is 1-1.5 g/kg.
• Onset and duration of action: Maximum hypotensive effect occurs in 1 hour and lasts 4-5 hours.
• Toxicity: Nausea, vomiting, and headache occasionally occur.
• Comment: Oral administration and the absence of diuretic effect are significant advantages of glycerin over the other hyperosmotic agents.

Isosorbide (Ismotic)

• Preparation: 45% solution.
• Dosage: 1.5 g/kg orally.
• Onset and duration of action: Similar to glycerin.
• Comment: Unlike glycerin, isosorbide does not produce calories or elevated blood sugar. Other side reactions similar to glycerin. Each 220 mL of isosorbide contains 4.6 meq of sodium.

Mannitol (Osmitrol)

• Preparation: 5-25% solution for injection.
• Dosage: 1.5-2 g/kg intravenously, usually in 20% concentration.
• Onset and duration of action: Maximum hypotensive effect occurs in about 1 hour and lasts 5-6 hours.
• Comment: Problems with cardiovascular overload and pulmonary edema are more common with this agent because of the large fluid volumes required.

Urea (Ureaphil)

• Preparation: 30% solution of lyophilized urea in invert sugar.
• Dosage: 1-1.5 g/kg intravenously.
• Onset and duration of action: Maximum hypotensive effect occurs in about 1 hour and lasts 5-6 hours.
• Toxicity: Accidental extravasation at the injection site may cause local reactions ranging from mild irritation to tissue necrosis.

TOPICAL CORTICOSTEROIDS

Indications

Topical corticosteroid therapy is indicated for inflammatory conditions of the anterior segment of the globe. Some examples are allergic conjunctivitis, uveitis, episcleritis, scleritis, phlyctenulosis, superficial punctate keratitis, interstitial keratitis, and vernal conjunctivitis.

Administration & Dosage

The corticosteroids and certain derivatives vary in their anti-inflammatory activity. The relative potency of prednisolone to hydrocortisone is 4 times; of dexamethasone and betamethasone, 25 times. The side effects are not decreased with the higher-potency drugs even though the therapeutic dosage is lower.

The duration of treatment will vary with the type of lesion and may extend from a few days to several months.

Initial therapy for a severely inflamed eye consists of instilling drops every 1 or 2 hours while awake. When a favorable response is observed, gradually reduce the dosage and discontinue as soon as possible.

Caution: The steroids enhance the activity of the herpes simplex virus, as shown by the fact that perforation of the cornea occasionally occurs when they are used in the eye for treatment of herpes simplex keratitis. Corneal perforation was an extremely rare complication of herpes simplex keratitis before the steroids came into general use. Other side effects of local steroid therapy are fungal overgrowth, cataract formation (unusual), and open-angle glaucoma (common). These effects are produced to a lesser degree with systemic steroid therapy. Any patient receiving local ocular corticosteroid therapy or long-term systemic corticosteroid therapy should be under the care of an ophthalmologist.

The following is a partial list of the available topical corticosteroids for ophthalmologic use:

• Hydrocortisone ointment, 0.5%, 0.12%, 0.125%, and 1%.
• Prednisolone acetate suspension, 0.125% and 1%.
• Prednisolone sodium phosphate solution, 0.125% and 1%.
• Dexamethasone sodium phosphate suspension, 0.1%; ointment, 0.05%.
• Medrysone suspension, 1%.
• Fluorometholone suspension, 0.1% and 0.25%; ointment, 0.1%.
• Rimexalone suspension, 1%.

MIXTURES OF CORTICOSTEROIDS & ANTI-INFECTIVE AGENTS

There are numerous commercial products containing fixed-dose combinations of corticosteroids and one or more anti-infective agents. They are used by ophthalmologists chiefly to treat conditions in which both agents may be required, eg, marginal keratitis due to a combined staphylococcal infection and allergic reaction, blepharoconjunctivitis, and phlyctenular keratoconjunctivitis. They are also used postoperatively.

These mixtures should not be used to treat conjunctivitis or blepharitis due to unknown causes. They should not be used as substitutes solely for anti-infective agents but only when a clear indication for corticosteroids exists as well. Mixtures of steroids and anti-infective agents may cause all of the same complications that occur with the topical steroid preparations alone.

NONSTEROIDAL ANTI-INFLAMMATORY AGENTS (NSAIDS)

Oral NSAIDs-indomethacin 75 mg daily or ibuprofen 600 mg daily-are the first-line treatment for scleritis. Gastric irritation and hemorrhage are a risk and may require prophylactic treatment with misoprostol, 100-200 g orally four times a day, or a proton pump inhibitor. Topical ophthalmic preparations of several NSAIDs have been developed and have become popular in the past few years. They provide ocular bioavailability with little toxicity. These agents act primarily by blocking prostaglandin synthesis through inhibition of cyclooxygenase, the enzyme catalyzing the conversion of arachidonic acid to prostaglandins. Certain NSAIDs also may limit the arachidonic acid available for leukotriene production.

Some ophthalmologists use combinations of topical corticosteroids and NSAIDs to manage ocular inflammation, but the value of adding NSAIDs to adequate steroid therapy is not established. A number of ophthalmologists believe that by using an NSAID, the steroid treatment can be reduced.

Currently, flurbiprofen (Ocufen), 0.03%, and suprofen (Profenal), 1%, have been approved by the Food and Drug Administration for the inhibition of miosis during cataract surgery. Ketorolac (Acular), 0.5%, is approved for use in seasonal allergic conjunctivitis. Diclofenac (Voltaren), 0.1%, is approved for treatment of postoperative inflammation following cataract surgery and for relief of pain and photophobia in patients undergoing laser corneal refractive surgery (PRK). Another preparation, indomethacin suspension (Indocid), 1%, is not available in the USA but is used in some parts of the world to treat cystoid macular edema, to reduce miosis during cataract surgery, and to treat inflammation following trauma, including cataract surgery.

OTHER DRUGS USED IN THE TREATMENT OF ALLERGIC CONJUNCTIVITIS

Cromolyn Sodium (Crolom)

• Preparation: Solution, 4%.
• Dosage: 1 drop four to six times a day.
• Comment: Cromolyn is useful in the treatment of many types of allergic conjunctivitis. Response to therapy usually occurs within a few days but sometimes not until treatment is continued for several weeks. Cromolyn acts by inhibiting the release of histamine and SRS-A, slow-reacting substance of anaphylaxis from mast cells. It is not useful in the treatment of acute symptoms.

Lodoxamide Tromethamine (Alomide)

• Preparation: Solution, 0.1%.
• Dosage: 1 drop four times a day.
• Comment: Lodoxamide is a mast cell stabilizer that inhibits type 1 immediate hypersensitivity reactions. It is indicated in the treatment of allergic reactions of the external ocular tissues, including vernal conjunctivitis and vernal keratitis. As with cromolyn, a therapeutic response does not usually occur until after a few days of treatment.

Olapadine Hydrochloride (Patanol)

• Preparation: Solution, 0.1%.
• Dosage: Twice a day at intervals of 6-8 hours.
• Comment: Olapatadine has both antihistamine and mast cell stabilizing actions.

Levocabastine Hydrochloride (Livostin)

• Preparation: Suspension, 0.05%.
• Dosage: One drop four times a day.
• Comment: Levocabastine is a selective, potent histamine H₁-receptor antagonist. It is useful in reducing acute symptoms of allergic conjunctivitis. Relief of symptoms occurs within minutes after application and lasts up to 2 hours.

Vasoconstrictors & Decongestant

These categories of drugs (see below) are also of interest in the treatment of allergic conjunctivitis.

ANTI-INFECTIVE OPHTHALMIC DRUGS

1. TOPICAL ANTIBIOTIC SOLUTIONS & OINTMENTS

Antibiotics are commonly used in the treatment of external ocular infection, including bacterial conjunctivitis, hordeola, marginal blepharitis, and bacterial corneal ulcers. The frequency of use is related to the severity of the condition. Antibiotic treatment of intraocular infection is set forth in Table 3-1.

Table 3-1: Usual adult dose of selected antimicrobials in endophthalmitis.^1,2

Bacitracin, neomycin, polymyxin, erythromycin, tetracycline, gentamicin, and tobramycin are the most commonly used topical antibiotics. They are used separately and in combination as solutions and as ointments.

Bacitracin

• Preparation: Ointment, 500 units/g. Commercially available in combinations with polymyxin B.
• Comment: Most gram-positive organisms are sensitive to bacitracin. It is not used systemically because of its nephrotoxicity.

Erythromycin

Erythromycin ointment, 0.5% is an effective agent, particularly in staphylococcal conjunctivitis. It may be used instead of silver nitrate in prophylaxis of ophthalmia neonatorum.

Neomycin

• Preparations: Solution, 2.5 and 5 mg/mL; ointment, 3.5-5 mg/g. Commercially available in combinations with bacitracin and polymyxin B.
• Dosage: Apply ointment or drops three or four times daily. Solutions containing 50-100 mg/mL have been used for corneal ulcers.
• Comment: Effective against gram-negative and gram-positive organisms. Neomycin is usually combined with some other drug to widen its spectrum of activity. It is best known in ophthalmologic practice as Neosporin, both in ointment and solution form, in which it is combined with polymyxin and bacitracin. Contact skin sensitivity develops in 5% of patients if the drug is continued for longer than a week.

Polymyxin B

• Preparations: Ointment, 10,000 units/g; suspension, 10,000 units/mL. Commercially available in combination with bacitracin and neomycin.
• Comment: Effective against many gram-negative organisms.

2. TOPICAL PREPARATIONS OF SYSTEMIC ANTIBIOTICS

Topical use of the antibiotics commonly used systemically should be avoided if possible, because sensitization of the patient may interfere with future systemic use. However, in certain instances clinical judgment overrides this principle if the drug is particularly effective locally and the disorder is serious. A prime example of this is tetracycline in the treatment of trachoma, the commonest eye infection in the world.

Fluoroquinolones (ciprofloxacin, norfloxacin) have recently become available for ophthalmic use. These agents are effective against a wide variety of gram-positive and gram-negative ocular pathogens, including Pseudomonas aeruginosa. They have been used principally for the treatment of corneal ulcers but have also been administered for the treatment of resistant bacterial conjunctivitis.

Tetracyclines

• Preparations: Suspension, 10 mg/mL; ointment, 10 mg/g.
• Comment: Tetracycline, oxytetracycline, and chlortetracycline have limited uses in ophthalmology because their effectiveness is so often impaired by the development of resistant strains. Solutions of these compounds are unstable with the exception of Achromycin in sesame oil, which is widely used in the treatment of trachoma. Ointment may be used for prophylaxis of ophthalmia neonatorum.

Gentamicin (Garamycin, Genoptic, Gentacidin, Gentak)

• Preparations: Solution, 3 mg/mL; ointment, 3 mg/g.
• Comment: Gentamicin is widely accepted for use in serious ocular infections, especially corneal ulcers caused by gram-negative organisms. It is also effective against many gram-positive staphylococci but is not effective against streptococci. Many strains of bacteria resistant to gentamicin have developed.

Tobramycin (Tobrex, Aktop)

• Preparations: Solution, 3 mg/mL; ointment, 3 mg/g.
• Comment: Similar antimicrobial activity to gentamicin but more effective against streptococci. Best reserved for treatment of Pseudomonas keratitis, for which it is more effective.

Chloramphenicol (Chloromycetin, Chloroptic)

• Preparations: Solution, 5 and 10 mg/mL; ointment, 10 mg/g.
• Comment: Chloramphenicol is effective against a wide variety of gram-positive and gram-negative organisms. It rarely causes local sensitization, but cases of aplastic anemia have occurred with long-term therapy.

Ciprofloxacin (Ciloxan)

• Preparation: Solution, 3 mg/mL.
• Dosage: For treatment of conjunctivitis, 1 drop every 2-4 hours. For treatment of corneal ulcers, 1 drop every 15-30 minutes for the first day, 1 drop every hour the second day, and 1 drop every 4 hours thereafter.

Norfloxacin (Chibroxin)

• Preparation: Solution, 3 mg/mL.
• Dosage: For conjunctivitis, same as that of ciprofloxacin.

Ofloxacin (Ocuflox)

• Preparation: Solution, 3 mg/mL.
• Dosage: For treatment of bacterial conjunctivitis, 1 drop every 2-4 hours for 2 days, then 1 drop four times a day.

3. COMBINATION ANTIBIOTIC AGENTS

Several ophthalmic preparations are available that contain a mixture of antibiotics and bacteriostatic agents (Table 3-2).

Table 3-2: Some combination antibiotic preparations.

4. SULFONAMIDES

The sulfonamides are the most commonly used drugs in the treatment of bacterial conjunctivitis. Their advantages include (1) activity against both gram-positive and gram-negative organisms, (2) relatively low cost, (3) low allergenicity, and (4) the fact that their use is not complicated by secondary fungal infections, as sometimes occurs following prolonged use of antibiotics.

The commonest sulfonamides employed are sulfisoxazole and sulfacetamide sodium.

Sulfacetamide Sodium (Various)

• Preparations: Ophthalmic solution, 10%, 15%, and 30%; ointment, 10%.
• Dosage: Instill 1 drop frequently, depending upon the severity of the conjunctivitis.

Sulfisoxazole (Gantrisin)

• Preparations: Ophthalmic solution, 4%; ointment, 4%.
• Dosage: As for sulfacetamide sodium (above).

5. TOPICAL ANTIFUNGAL AGENTS

Natamycin (Natacyn)

• Preparation: Suspension, 5%.
• Dosage: Instill 1 drop every 1-2 hours.
• Comment: Effective against filamentary and yeast forms. Initial drug of choice for most mycotic corneal ulcers.

Nystatin (Mycostatin)

Nystatin is not available in ophthalmic ointment form, but the dermatologic preparation (100,000 units/g) is not irritating to ocular tissues and can be used in the treatment of fungal infection of the eye.

Amphotericin B (Fungizone)

Amphotericin B is more effective than nystatin but not available in ophthalmic ointment form. The dermatologic preparation is highly irritating. A solution (1.5-8 mg/mL of distilled water in 5% dextrose) must be made up in the pharmacy from the powdered drug. Many patients have extreme ocular discomfort following application of this drug.

Miconazole (Monistat)

A 1% solution is available in the form of an intravenous preparation that may be applied directly into the eye. The drug is not available in an ophthalmologic form.

Fluconazole (Diflucan)

An 0.2% parenteral preparation is available and may be applied into the eye. No ophthalmologic product is available.

6. ANTIVIRAL AGENTS

Idoxuridine (Herplex)

• Preparations: Ophthalmic solution, 0.1%; ointment, 0.5%.
• Dosage: 1 drop every hour during the day and every 2 hours at night. With improvement (as determined by fluorescein staining), the frequency of instillation is gradually reduced. The ointment may be used four to six times daily, or the solution may be used during the day and the ointment at bedtime.
• Comment: Used in the treatment of herpes simplex keratitis. Epithelial infection usually improves within a few days. Therapy should be continued for 3 or 4 days after apparent healing. Many ophthalmologists still prefer to denude the affected corneal epithelium and not use idoxuridine.

Vidarabine (Vira-A)

• Preparation: Ophthalmic ointment, 3%.
• Dosage: In herpetic epithelial keratitis, apply four times daily for 7-10 days.
• Comment: Vidarabine is effective against herpes simplex virus but not other ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) viruses. It is effective in some patients unresponsive to idoxuridine. Vidarabine interferes with viral DNA synthesis. The principal metabolite is arabinosylhypoxanthine (Ara-Hx). The drug is effective against herpetic corneal epithelial disease and has limited efficacy in stromal keratitis or uveitis. It may cause cellular toxicity and delay corneal regeneration. The cellular toxicity is less than that of idoxuridine.

Trifluridine (Viroptic)

• Preparation: Solution, 1%.
• Dosage: 1 drop every 2 hours (maximum total, 9 drops daily).
• Comment: Acts by interfering with viral DNA synthesis. More soluble than either idoxuridine or vidarabine and probably more effective in stromal disease.

Acyclovir (Zovirax)

• Preparation: Capsules, 200 mg.
• Comment: Acyclovir is an antiviral agent with inhibitory activity against herpes simplex types 1 and 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus. It is phosphorylated initially by virus-specific thymidine kinase to acyclovir monophosphate and then by cellular kinases to acyclovir triphosphate, which inhibits viral DNA polymerase. Thus, there is a marked selectivity for virus-infected cells. Acyclovir has low toxicity. No commercial ophthalmic preparation is currently available in the USA; a topical product available for treatment of genital herpes should not be used in the eye. An oral preparation is available that may be used for treatment of selected herpes zoster ocular infections.

DIAGNOSTIC DYE SOLUTIONS

Fluorescein Sodium

• Preparations: Solution, 2%, in single-use disposable units; as sterile paper strips; as 10% sterile solution for intravenous use in fluorescein angiography.
• Dosage: 1 drop.
• Comment: Used as a diagnostic agent for detection of corneal epithelial defects, in applanation tonometry, and in fitting contact lenses.

Rose Bengal

• Preparation: Solution, 1%, and strips, 1.3 mg.
• Dosage: 1 drop.
• Comment: Used in diagnosis of keratoconjunctivitis sicca; the mucous shreds and devitalized corneal epithelium stain with rose bengal.

TEAR REPLACEMENT & LUBRICATING AGENTS

Methylcellulose and related chemicals, polyvinyl alcohol and related chemicals, and gelatin are used in the formulation of artificial tears, ophthalmic lubricants, contact lens solutions, and gonioscopic lens solutions. These agents are particularly useful in the treatment of keratoconjunctivitis sicca. (See Chapter 4.)

To increase viscosity and prolong corneal contact time, methylcellulose is sometimes added to eye solutions (eg, pilocarpine). Preservative-free preparations are available for use in patients with sensitivities to these substances.

VASOCONSTRICTORS & DECONGESTANTS

There are many commercially available OTC, over-the-counter ophthalmic vasoconstrictive agents. The active ingredients in these agents usually are either ephedrine 0.123%, naphazoline 0.012-0.1%, phenylephrine 0.12%, or tetrahydrozoline 0.05-0.15%.

These agents constrict the superficial vessels of the conjunctiva and relieve redness. They also relieve minor surface irritation and itching of the conjunctiva, which can represent a response to noxious or irritating agents such as smog, swimming pool chlorine, etc. Products also are available that contain an antihistamine, antazoline phosphate 0.25-0.5%, or pheniramine maleate 0.3%.

CORNEAL DEHYDRATING AGENTS

Dehydrating solutions and ointments applied topically to the eye reduce corneal edema by creating an osmotic gradient in which the tear film is made hypertonic to the corneal tissues. Temporary clearing of corneal edema results.

• Preparations: Anhydrous glycerin solution (Ophthalgan), hypertonic sodium chloride 2% and 5% ointment and solution (Absorbonac, Ak-NaCl, Hypersal, Muro-128).
• Dosage: 1 drop of solution or ¼-inch strip of ointment to clear cornea. May be repeated every 3-4 hours.

 
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10.1036/1535-8860.ch3

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