Ophthalmologic Medications: Pearls & Pitfalls for the ED

Author: Brit Long, MD (@long_brit, SAUSHEC EM) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Stephen Alerhand, MD (@SAlerhand)

Emergency physicians manage ophthalmologic conditions daily, and we possess a vast array of medications to prescribe. This variety of medications and their indications can result in discomfort with ophthalmologic medications. This post examines the different classes of emergent ophthalmological medications, including dosing and indications.^1-6

Your first patient of the day is an 18-year-old male who was playing baseball with his friends. He was sliding into second base, when he felt something fly into his right eye. He immediately began rubbing the eye, and he now has diffuse pain. Exam reveals diffuse redness of the right eye, with normal visual acuity. Your fluorescein exam reveals a small, peripheral corneal abrasion. What medication(s) can you provide?

Anesthetics
Two types of anesthetics exist for use in ophthalmologic conditions: esters and amides. The most common esters are proparacaine (0.5%) and tetracaine (0.5%). Tetracaine lasts approximately 30 minutes once applied. In comparison, proparacaine lasts 15 minutes and is slightly more irritating and slower in onset.
Color Cap: WHITE
Mechanism of action: Anesthetics function as sodium channel blockers, which decrease depolarization and action potential propagation.
Indications: Used for topical anesthesia, assisting with examination and procedures. These medications can be used to help differentiate corneal causes of symptoms versus other causes. Use in an outpatient setting is controversial for pain control; however, diluting the solution is feasible and likely will not cause delayed healing or toxicity.^1-3
Dosing: One to two drops in the ED.
Considerations: Recent literature supports increased patient satisfaction with local anesthetics within a 24 hour period and no evidence of difference in corneal healing. Literature and FOAM resources support the use of diluting the 0.5% concentration into 0.05%. This can be done using a 10cc flush, ejecting 1 cc of the saline, and replacing this with 1 cc of the anesthetic.^7,8

A 7-year-old male presents with his mother for two days of diffuse, bilateral eye redness and “green” drainage. He recently recovered from an upper respiratory infection. His exam, including VS, visual acuity, and fluorescein staining, are normal. You are concerned about bacterial conjunctivitis. What are your choices for antibiotics?

Antimicrobials
Topical antibiotics are often over-prescribed. However, they are indicated for a number of ophthalmic diagnoses including bacterial conjunctivitis, corneal ulcers, and blepharitis. Antibiotics are administered as either solutions or ointments. Drops are rapidly absorbed and require frequent instillation. Ointments have longer duration and require less frequent administration. However, they cause blurred vision when applied.
Color Cap: TAN
Mechanism of Action: A variety of mechanisms exist for these medications. These are shown in Table 1.
Indications: As discussed previously, indications include bacterial conjunctivitis, corneal ulcers, and blepharitis.
Dosing: Usually dependent on specific agent, with one to two drops applied one to four times per day.
Considerations: Please see Table 1.

Table 1 – Specific Antibiotic Medications⁴

Topical antivirals (idoxuridine, trifluridine, and ganciclovir) are used for treatment of herpes simplex keratitis but should not be given without consultation with an ophthalmologist. Dosing includes one drop every hour for idoxuridine, one drop every two hours for trifluridine, and one drop five times per day for ganciclovir.

Antibiotic-steroid combination medications exist, but should not be used in the ED. Leave these to the ophthalmologist.

Your next patient is a 32-year-old female with deep “boring” eye pain. Your exam reveals “cells and flare” on your slit lamp with normal visual acuity and no fluorescein uptake, consistent with iritis. What medication(s) can you use?

Mydriatics and Cycloplegics
Mydriatics and cycloplegics function to dilate the eye. Mydriatic medications accomplish this by paralyzing the iris sphincter, which causes dilation without affecting accommodation. On the other hand, cycloplegics paralyze both the iris sphincter and the ciliary muscles, causing dilation and affecting accommodation. Phenylephrine (2.5%) is a common dilating agent with onset 15 minutes, lasting for 3-4 hours. Cycloplegics are often used for conditions causing inflammation of the eye. Several cycloplegics include:

• Cyclopentolate has an onset of 30-60 minutes with duration of approximately 24 hours.
• Tropicamide has an onset of 15-20 minutes with duration of approximately 6 hours.
• Homatropine and atropine have a duration of days to weeks and probably have little role in the ED due to this length of action.

Color Cap: RED
Mechanism of Action: Mydriatics are sympathomimetic agents that paralyze the iris sphincter. Cycloplegics are parasympatholytic agents that paralyze the iris sphincter and the ciliary muscles.
Indications: These medications are helpful for evaluating painless monocular vision complaints such as vision loss. They can be used to treat ciliary spasm, decreasing ocular pain, in iritis and deep corneal ulcers.
Dosing: One drop in the ED. These medications are usually required once per day if prescribed for home use.
Considerations: These medications are contraindicated in patients with suspicion for increased intraocular pressure, especially in acute angle closure glaucoma, as well as in the presence of shallow anterior chamber or concern for ruptured globe.

A 63-year-old female with near-sightedness presents with sudden, severe left-sided headache and eye pain after leaving a movie theater. Her vision is cloudy in the left eye. Visual acuity in the left eye is 20/400, with correction. Her intraocular pressure is 52 mm Hg in the left eye and 18 mm Hg in the right. Her left pupil is mid-dilated, and the cornea appears cloudy. What treatments are necessary?

Adrenergic Agents
Topical adrenergic agents include beta-antagonists (timolol, betaxolol) and alpha-2-agonists (apraclonidine, brimonidine).

Beta blockers
Color Cap: YELLOW
Mechanism of Action: These medications reduce intraocular pressure through decreasing aqueous humor secretion by the ciliary body.
Indications: This class is only used in the setting of acute angle closure glaucoma.
Dosing: One drop two to three times per day (once in the ED).
Considerations: The provider must be wary of cardiopulmonary effects including hypotension, syncope, heart block, and worsening of asthma. Of note, combination beta blockers may have a dark blue cap.

Alpha agonists
Color Cap: PURPLE
Mechanism of action: Similar to topical beta blockers, these medications decrease aqueous humor production, decreasing intraocular pressure.
Indications: Acute angle closure glaucoma.
Dosing: One drop three times per day (once in the ED).
Combigan Ophthalmic Solution® is a combination alpha-2-agonist and beta blocker used for acute angle closure glaucoma, with one drop provided every 12 hours.

Carbonic anhydrase inhibitors
Medications in this class include dorzolamide and brinzolamide (Trusopt and Azopt). They repress carbonic anhydrase, reducing pressure in the eye through reduction in aqueous humor production.
Color Cap: ORANGE
Mechanism of Action: These medications reduce intraocular pressure through decreasing aqueous humor secretion by the ciliary body.
Indications: This class is only used in the setting of acute angle closure glaucoma.
Dosing: One drop three times per day.
Considerations: This class should not be used in patients with sickle cell disease or trait, which may lead to acute angle closure glaucoma.

Prostaglandin analogues
This class consists of travoprost, latanoprost, bimatoprost, and tafluprost. These medications reduce intraocular pressure by increasing outflow of aqueous humor.
Color Cap: Turquoise
Mechanism of Action: These medications reduce intraocular pressure through increasing outflow of aqueous humor.
Indications: This class is used for acute angle closure glaucoma.
Dosing: One drop dosed one to four times per day, specific to the agent used.
Considerations: The provider must be wary of cardiopulmonary effects including hypotension, syncope, heart block and worsening of asthma.

Miotics (Cholinergic)
In emergency medicine, the most common use for miotic agents is acute angle closure glaucoma. The most common miotic is pilocarpine (2%), which facilitates drainage of the aqueous humor.
Color Cap: DARK GREEN
Mechanism of Action: Miotics cause pupillary constriction, pulling the iris back from an anterior position.
Indications: This class of medication is used in acute angle closure glaucoma.
Dosing: Two drops three to four times per day.
Considerations: In the ED, this medication will be used in acute angle closure glaucoma but is only efficacious once the intraocular pressure is less than 40 mm Hg. They should only be applied after initial measures are completed, and both eyes should be medicated with pilocarpine in the setting of acute angle closure glaucoma. In the setting of cataract surgery, it may be better to dilate the eye and avoid this agent.

Systemic Medications
Several systemic medications can be used in ophthalmologic conditions, specifically acute angle closure glaucoma.

– Hyperosmotic agents
Mannitol 1-2 g/kg IV – 20% solution reduces fluid volume in the eye, which decreases intraocular pressure. This medication is indicated in acute angle closure glaucoma.

– Carbonic anhydrase inhibitor
Acetazolamide 500 mg IV/PO decreases secretion of aqueous humor by the ciliary body, reducing intraocular pressure. The medication is indicated in acute angle closure glaucoma and refractory retinal artery occlusion. However, it is contraindicated in sickle cell disease. The change in intraocular pH can increase sickling of RBCs in anterior chamber, decreasing aqueous outflow and increasing IOP. Acetazolamide may also cause worsening renal function in those with preexisting renal disease.

You have a 43-year-old female who just moved into the area. She has a history of severe allergies to dust, pollen, ragweed, and oak, and she is presenting with bilateral eye redness and irritation, with nasal congestion and drainage. Her VS are normal, and her exam is consistent with allergic conjunctivitis. What medication(s) can you prescribe?

Antihistamine/decongestant
This medication class is useful for conjunctival congestion and pruritis. Medications include Naphazoline and pheniramine (Naphcon-A® and Visine A®).
Color Cap: OLIVE GREEN
Mechanism of Action: This class works as histamine receptor antagonists.
Indications: Medications are used for conjunctival congestion or pruritis.
Dosing: One drop two times per day.
Considerations: This class should not be used for over 72 hours. They should be avoided in narrow angle glaucoma, hypertension, and contact lens use.

Non-steroidal anti-inflammatory drugs
These medications provide another option for pain and inflammation control for ophthalmologic complaints. Medications include Ketorolac, Bromfenac, Nepafenac, Diclofenac sodium.
Color Cap: GRAY
Mechanism of Action: These agents reversibly inhibit cyclooxygenase-1 and 2 (COX-1 and 2 enzymes), which decrease formation of prostaglandin. They also decrease cytokine levels and immune cellular activation.
Indications: This class can be used in allergic conjunctivitis, corneal abrasions, and UV keratitis.
Dosing: Dependent on the specific agent. Ketorolac and diclofenac are given one drop three to four times per day, while bromfenac is given one drop per day.
Considerations: These agents may enhance topical glucocorticoid effects.

Mast cell stabilizers
These agents are primarily used in the setting of allergic conjunctivitis. Medications include Nedocromil sodium (Alocril Ophthalmic Solution®), Pemirolast potassium (Alamast Ophthalmic Solution®), Lodoxamide tromethamine (Alomide Ophthalmic Solution®), and Cromolyn sodium (Cromolyn Sodium Ophthalmic Solution®). These medications are not useful for acute symptoms, as full efficacy is not reached until at least 5 days of use.⁹
Mechanism of Action: This medication class functions to stabilize mast cell membranes, preventing the release of histamine and leukotrienes.
Indications: These are used for allergic conjunctivitis.
Dosing: One drop two times per day.
Considerations: Efficacy is not observed until 5-14 days of use.

H1-antagonists
Similar to mast cell stabilizers, these topical medications are used for allergic conjunctivitis. Medications include Bepotastine besilate (Bepreve Ophthalmic Solution®), Epinastine hydrochloride (Elestat Ophthalmic Solution®), Emedastine difumarate (Emadine Ophthalmic Solution®), Alcaftadine (Lastacraft Ophthalmic Solution®), and Azelastine hydrochloride (Optivar Ophthalmic Solution®)
Mechanism of Action: These medications are H1-receptor antagonists.
Indications: Used for allergic conjunctivitis.
Dosing: One drop two times per day.
Considerations: Combination agents consisting of H1 antagonist-mast cell stabilizer ophthalmologic medications include Olopatadine hydrochloride (Pataday Ophthalmic Solution®, Patanol Ophthalmic Solution®).

References/Further Reading:

1. Nash, E.A. and C.E. Margo, Patterns of emergency department visits for disorders of the eye and ocular adnexa. Arch Ophthalmol, 1998. 116(9): p. 1222-6.
2. Sklar, D.P., J.E. Lauth, and D.R. Johnson, Topical anesthesia of the eye as a diagnostic test. Annals of emergency medicine, 1989. 18(11): p. 1209-11.
3. Waldman, N., I.K. Densie, and P. Herbison, Topical tetracaine used for 24 hours is safe and rated highly effective by patients for the treatment of pain caused by corneal abrasions: a double-blind, randomized clinical trial. Academic emergency medicine: official journal of the Society for Academic Emergency Medicine, 2014. 21(4): p. 374-82.
4. Walker RA and Adhikaris. Eye Emergencies. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. Ch. 241.
5. Sharma R and Brunette DD. Ophthalmology. Rosen’s Emergency Medicine, Chapter 71, 909-930.e2.
6. http://www.aao.org/about/policies/color-codes-topical-ocular-medications.
7. Swaminathan A et al. The Safety of Topical Anesthetics in the Treatment of Corneal Abrasions: A Review. J Emerg Med 2015 PMID: 26281814
8. Puls HA et al. Safety and Effectiveness of Topical Anesthetics in Corneal Abrasions: Systematic Review and Meta-Analysis. J Emerg Med 2015 [epub ahead of print]
9. Nizami RM. Treatment of ragweed allergic conjunctivitis with 2% cromolyn solution in unit doses. Ann Allergy 1981; 47:5.