Kimberly Schertzer
This chapter provides an overview of medications used to diagnose and treat common ocular conditions.
DIAGNOSTIC MEDICATIONS
Stains
These topical solutions reveal areas of corneal and conjunctival epithelial disruption.
Fluorescein stains are by far the most commonly used stains in the emergency department (ED). These stains highlight defective epithelium within the cornea and conjunctiva, with defective areas enhancing under cobalt blue light after staining. Single-use, sterile paper strips are preferred instead of the 2% solutions for convenience and concern about contamination of multiuse containers. Evaluation must happen quickly, as the ability to see stained areas is limited, usually only 1 to 3 minutes after application.
Other stains such as rose bengal, are not commonly used in the ED and may be irritating. Rose bengal stains devitalize epithelium and is useful for differentiating a herpetic corneal ulcer from a healing corneal abrasion.
Anesthetics
By providing temporary anesthesia, topical anesthetics facilitate eye examination as well as application of diagnostic drops. Most patients cannot tolerate either the application of ocular stains or testing of intraocular pressure (IOP) without topical anesthesia. Application of a topical anesthetic to the eye of a patient with a presumed corneal epithelial defect can be both therapeutic and diagnostic. The topical anesthetic provides patients immediate pain relief and supports the diagnosis of a corneal injury. Topical anesthetics are not for repetitive use, as they suppress protective ocular blink reflexes, have been linked to delayed corneal healing, and may cause an anesthetic-induced keratitis.
Tetracaine hydrochloride (Pontocaine) (0.5% to 1% solution) may initially sting. Its effect lasts for approximately 15 minutes.
Proparacaine hydrochloride (Ophthetic, Ophthaine) (0.5% solution) is less irritating than other solutions.
Mydriatics and Cycloplegics (Red Cap)
These agents are used diagnostically or therapeutically to dilate the pupil (mydriasis) and/or to paralyze the ciliary body (cycloplegia). This effect facilitates evaluation of the internal ocular structures and blocks accommodation. In addition, these agents prevent formation of synechiae (adhesions of the iris to the lens and cornea) by reducing intraocular inflammation through stabilization of the blood–aqueous barrier and by physically pulling the iris away from greater contact with the anterior lens surface. Mydriatic agents are stored in containers capped in red. The duration of drug effects listed below are for normal, noninflamed eyes.
Phenylephrine hydrochloride (Neo-Synephrine, Mydfrin) constricts the surface vessels and dilates the pupil without causing cycloplegia. The 2.5% solution is recommended because of increased systemic (cardiovascular) side effects with 10% solution. The effect lasts approximately 3 hours.
Tropicamide (Mydriacyl 0.5% and 1%) provides short-term dilation of the pupil, plus cycloplegia (lasting 4 to 6 hours). Tropicamide is relatively easy to reverse if there is a concern about iatrogenic angle-closure glaucoma. It is commonly used by ophthalmologists.
Cyclopentolate hydrochloride (Cyclogyl 0.5%, 1%, and 2%) is the best short-term cycloplegic for determining refractive error; it may last from 6 to 24 hours.
Homatropine hydrobromide (1%, 2%, and 5%) lasts for several days. It is a useful short-term mydriatic and cycloplegic for low-level inflammation (iritis) caused by trauma or abrasions.
Scopolamine hydrobromide (Hyoscine 0.25%) lasts between 4 and 7 days; it is more effective for long-term inflammation seen postoperatively or in severe uveitis.
Atropine sulfate (0.25% to 2% solution, 0.5% and 1% ointment) lasts for 10 to 14 days; it is most commonly used postoperatively and in severe uveitis. It carries both corneal epithelial and systemic toxicities.
THERAPEUTIC AGENTS
Lubricants
Dry eyes may be the result of decreased tear production, systemic disease, environmental factors, medication effects, or inadequate lid function. Patients with dry eyes may complain of itching, blurred vision, burning, or a foreign-body sensation. Artificial lubricants temporarily restore the precorneal tear film and provide an effective but short-term treatment for dry eye-related symptoms.
Artificial tears are often used. Most of these formulations (Table 55.1) contain “thickening” agents (such as methylcellulose or polyvinyl alcohol), which prolong retention of the tears on the ocular surface. Most formulations contain preservatives to prevent contamination, but patients who find these preservatives irritating may opt for more expensive, single-use packets. Artificial tears are generally recommended for use every 4 to 6 hours but may be used as frequently as hourly if needed.
TABLE 55.1
Artificial Tear Preparations
Bland lubricating ointments (Lacri-Lube, Refresh P.M.) are more viscous than drops, making these agents useful for maximizing sleep-related lubrication or for patients with incomplete lid closure (e.g., those who have seventh cranial nerve palsy).
Antibiotics (Tan Cap)
The general principles of antibiotic therapy apply to topical antibiotics as well. See Table 55.2 for a detailed description of ocular antimicrobial agents.
TABLE 55.2
Antibiotics for Topical Use (Tan Cap)
Anti-Inflammatories
Both steroidal and nonsteroidal anti-inflammatories are available by prescription. These agents suppress ocular inflammation and allergic reactions both inside and outside the eye. Suppression of extraocular inflammation may prevent corneal scarring and permanent abnormalities in tear film. Within the eye, these agents may prevent scarring and the later development of glaucoma.
Steroid anti-inflammatory agents (Table 55.3) (pink cap) decrease inflammation. However, their use may be associated with significant side effects, including worsening of ocular infections and permanent visual loss. Some patients experience an increase in IOP within several weeks of using topical steroids. Topical steroids should be prescribed only after consultation with an ophthalmologist and assurance of reliable follow-up.
TABLE 55.3
Ocular Steroid Preparations (Pink Cap)
Nonsteroidal anti-inflammatory agents (gray cap) have limited systemic effects. These topical agents are useful in the treatment of pain associated with corneal abrasions or following refractive surgery.
Flurbiprofen 0.03% (Ocufen) is often used during surgery.
Diclofenac 0.1% (Voltaren) is used for postoperative inflammation following surgery. It also provides safe and effective analgesia for the initial treatment of traumatic corneal abrasions.
Ketorolac 0.5% (Acular) was developed for allergic conjunctivitis. Ketorolac may also be a useful adjunct in the treatment of corneal abrasions.
Antibiotic–Steroid Combinations
Antibiotic–steroid combinations are useful postoperatively. Multiple formulations are available that combine various concentrations of topical corticosteroids with broad-spectrum antibiotics. Antibiotic–steroid combinations should only be used with ophthalmologic consultation. They are available as both drop and ointment preparations and include these drugs:
TobraDex (Tobramycin 0.3%, Dexamethasone 0.1%)
Cortisporin (Neomycin, Polymyxin B, Hydrocortisone 1%)
Blephamide (Sulfacetamide 10%, Prednisolone acetate 0.2%)
Antiglaucoma Agents
To decrease IOP, most antiglaucoma agents (Table 55.4) either increase aqueous humor outflow or decrease its production, or both. In general, monotherapy with a prostaglandin analog or topical β-blocker is preferred, as each works effectively and results in relatively few side effects. The addition of a carbonic anhydrase inhibitor may be useful in further decreasing IOP.
TABLE 55.4
Antiglaucoma Medications
Prostaglandin analogs (turquoise cap) are the preferred initial therapeutic agent. By increasing aqueous humor outflow, these drugs lower IOP by 25% to 30%, although their time to initial efficacy is somewhat longer than with β-blockers. Prostaglandin analogs carry some adverse effects, including lash growth, periorbital skin hyperpigmentation, and irreversible iris hyperpigmentation, seen most commonly in patients with light or mixed irides. Tafuprost has recently been approved as a preservative-free prostaglandin analog, with similar efficacy as other drugs in its class.
Topical β-blockers (yellow or blue cap) decrease aqueous humor production and are commonly used in the treatment for glaucoma. They may cause adverse effects similar to those of systemic β-blockers (affecting the cardiopulmonary and central nervous systems) and should be avoided in patients with asthma, bradycardia, or severe chronic obstructive pulmonary disease. Betaxolol (β-1 cardioselective) is slightly less effective than nonselective β-blockers but exhibits fewer side effects because of its selectivity. As a class, topical β-blockers may have effects on libido and cause cardiac sensitivity.
Carbonic anhydrase inhibitors (orange cap) decrease aqueous humor production, but their use may be limited by potentially adverse effects. They may be oral or topical. Oral forms including acetazolamide and methazolamide decrease IOP nearly twice as much as topical forms but have significantly more adverse events, including renal calculi formation and hypokalemia. While these agents are sulfa-related, they are generally well tolerated by patients with sulfonamide allergies. In general, topical agents are less effective than oral ones, typically reducing IOP by 15% to 20%, but they have fewer adverse effects.
Topical α-2 agonists both decrease aqueous humor production and increase its outflow. Apraclonidine may cause tachyphylaxis and localized allergic reaction. Bromonide may cause respiratory depression in children younger than 2 years and should be avoided in this population. It may also cause systemic hypotension in children and infants. All ocular α-agonists are relatively contraindicated in patients taking monoamine oxidase inhibitors.
Adrenergic agents may be used for glaucoma. However, the rapid development of tolerance limits their use, and as a class they are less preferred than selective α-agonists.
Cholinergic agonists (green cap) may also be used as antiglaucoma agents. They increase outflow of aqueous humor but have no effect on its production. In general, they have been replaced by newer antiglaucoma drugs and their use is limited by local and systemic adverse effects. Cholinergic agonists may cause transient blurred vision and myopia. Still they are useful in some circumstances, such as the immediate treatment of acute angle-closure glaucoma.
Osmotic agents are not available in a topical form. In oral and parental form, they lower IOP by increasing the osmotic gradient between the blood and the eye. They can cause systemic hyperosmolarity and electrolyte imbalance. In addition, they may produce rebound IOP increases as they are eliminated from the body. The oral form is glycerol, which commonly causes nausea and vomiting, and because glycerin is gluconeogenic, should be used with caution in diabetic patients. The parenteral osmotic agent is mannitol. Both osmotic agents should be reserved for cases where acute, rapid IOP rises are not controlled by topical agents.
Allergy Medications
Environmental irritants including dust and pollen can cause redness, itching, chemosis, and increased tear production. Over-the-counter oral antihistamine–decongestant combinations often provide sufficient relief. If this conservative therapy fails, patients may find more symptomatic relief from topical antihistamines, nonsteroidal anti-inflammatory drugs (NSAIDs), and mast-cell inhibitors (Table 55.5). Topical steroids may also be considered but should be prescribed only after ophthalmologic consultation.
TABLE 55.5
Allergy Medications
Ocular decongestants whiten eyes and reduce conjunctival congestion and eyelid edema. They do not require a prescription and are very effective. This may cause some patients to delay seeking care for serious causes of red eyes. Chronic use results in tolerance and “rebound” vascular dilation. Some ocular decongestants contain a mild topical antihistamine (antazoline or pheniramine) and are distinguished by the suffix “-A” within the name. Though these antihistamine–decongestant combinations have a short duration of action, they may be more effective than either agent used individually.
Antihistamines are primarily H1-antagonists. They have both antihistaminic and anti-inflammatory effects. Some antihistamines also possess mast-cell–stabilizing effects.
Mast-cell stabilizers may effectively treat seasonal allergies, which are usually attributed to type I (IgE-mediated) hypersensitivity. By blocking the release of histamine and other vasoactive mediators from mast cells these agents may provide relief, although their onset of action is delayed (days to weeks).
Common Pitfalls
• Topical anesthetics are not for outpatient use, as they suppress protective ocular-blink reflexes, have been linked to delayed corneal healing, and may cause a toxic chemical keratitis.
• Topical steroids can lead to worsening of ocular infections and permanent visual loss; they should only be prescribed after consultation with an ophthalmologist.
• Although most topical ocular medications act locally, certain agents (such as β-blockers) may cause serious systemic side effects.
ACKNOWLEDGMENTS
The authors gratefully acknowledge the contributions of Geoffrey Broocker to the content of this chapter.
REFERENCES
1. Alfonso E, Crider J. Ophthalmic infections and their anti-infective challenges. Surv Ophthalmol. 2005;50:S1–S6.
2. Anonymous. Drugs for some common eye disorders. Treat Guidel Med Lett. 2012;10(123):79–86.
3. Bartlett J, Bennett E, Fiscella R, et al. Ophthalmic Drug Facts 2003. St. Louis, MO: Wolters Kluwer Co.; 2002.
4. Bisla K. Concentration dependent effects of lidocaine on corneal epithelial wound healing. Invest Ophthalmol Vis Sci. 1992;33:3029–3033.
5. Hemady RK, Chan AS, Nguyen AT. Immunosuppressive agents and nonsteroidal anti-inflammatory drugs for ocular immune and inflammatory disorders. Ophthalmol Clin North Am. 2005;18:511–528.
6. Kaiser PK, Pineda R. A study of topical nonsteroidal antiinflammatory drops and no pressure patching in the treatment of corneal abrasions. Ophthalmology. 1997;104:1353–1359.
7. Kunimoto DY, Kanitkar KD, Makar MS, eds. The Wills Eye Manual. 4th ed. New York, NY: Lippincott, Williams & Wilkins; 2004.
8. Langston DP. Manual of Ocular Diagnosis and Therapy. 5th ed. New York, NY: Lippincott, Williams & Wilkins; 2002.
9. Lee DA. Ocular hypotensive medications for the treatment of glaucoma. Ophthalmol Clin North Am. 2005;18:529–538.
10. Levinson BA, Rutzen AR. New antimicrobials in ophthalmology. Ophthalmol Clin North Am. 2005;18:493–509.
11. Patel KH, Javitt JC, Tielsch JM, et al. Incidence of acute angle closure glaucoma after pharmacologic mydriasis. Am J Ophthalmol. 1995;120:709–717.
12. Physician’s Desk Reference for Ophthalmology. 31st ed. Montvale, NJ: Thomson Medical Economics Data Production Company, 2002.
13. Sklar DP, Lauth JE, Johnson DR. Topical anesthesia of the eye as a diagnostic test. Ann Emerg Med. 1989;18:1209–1211.
14. Szucs PA, Nashed AH, Allegra JR, et al. Safety and efficacy of diclofenac ophthalmic solution in the treatment of corneal abrasions. Ann Emerg Med. 2000; 35:131–137.
15. Trattler WB, Luchs J, Majmuder P. Elestat (Epinastine HCl Ophthalmic Solution 0.05%) as a therapeutic for allergic conjunctivitis. Int Ophthalmol Clin. 2006; 46(4):87–99.
16. Weaver CS, Terrell KM. Evidence-based emergency medicine. Update: Do ophthalmic nonsteroidal anti-inflammatory drugs reduce the pain associated with simple corneal abrasion without delaying healing? Ann Emerg Med. 2003; 41:134–140.
17. Arthur S, Cantor LB. Update on the role of alpha-agonists in glaucoma management. Exp Eye Res. 2011;93:271–283.