15

Mydriatics and Cycloplegics

Ashok Garg

Introduction

Mydriatics are drugs which dilate the pupil while cycloplegics are agents which cause paralysis of ciliary muscle (paralysis of accommodation). Mydriatics usually produce paralysis of ciliary muscle in greater or lesser degree.

• All these drugs when instilled into the conjunctival sac are rapidly absorbed through the cornea and become effective in the inner eye.

Currently two classes of drugs: (i) adrenergic agonist, and (ii) cholinergic antagonist are available for mydriatic purpose. For most dilatation procedures, the adrenergic or anticholinergic agents can be used either alone or in combination for maximum mydriasis. Anticholinergic agents used topically in the eye for the purpose of inhibiting accommodation are termed cycloplegics. Their primary use is for cycloplegic refraction and in the treatment of uveitis. Since these agents also inhibit action of the iris sphincter muscle they are effective mydriatics and are commonly used for routine pupillary dilatation.

Mydriatic Adrenergic Agents (Sympathomimetic Agents)

The effect of sympathomimetic agents on the eye include pupil dilatation, increase in the outflow of aqueous humor and vasoconstriction (α-adrenergic effects), relaxation of ciliary muscle and decrease in the formation of aqueous humor. The various agents of this group used in ophthalmology are as follows.

Adrenaline (Epinephrine)

Adrenaline acts on dilator fibers and directly produces dilatation after the instillation of four drops of 1:1000 solution, the instillation being repeated in 5 minutes. It is mainly used in the treatment of open angle glaucoma.

Adrenaline may be combined with procaine and atropine as a subconjunctival injection to achieve mydriasis in severe cases of iritis.

Cocaine Hydrochloride

Cocaine hydrochloride is an alkaloid and is used as cocaine hydrochloride 2 percent and 4 percent drops. It acts as a mydriatic by inhibiting the action of amine oxidase. It is toxic

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to the cells of corneal epithelium and this effect may be used to advantage in that the damage to the epithelium allows a greater penetration of drugs through the cornea.

It does not cause dilatation of pupil and pupil continues to react to light even after prolonged application. It is, therefore, ineffective when the sympathetic nerve is paralyzed.

Phenylephrine

Phenylephrine is one of the most common sympathomimetic agents (α-adrenergic stimulant) used in ophthalmology for dilatation purposes. It is used in the form of hydrochloride. It acts directly on the α-receptors of the dilator pupillae causing pupil dilatation. Following topical instillation, it acts on the dilator muscles and smooth muscles or conjunctival arterioles causing pupillary dilatation and blanching of conjunctiva. Its action can be reversed by thymoxamine 0.1 percent.

Indications For pupil dilatation in diagnostic purposes (for complete fundus exam) and in various pathological conditions of the eye [in uveitis (posterior synechiae)], open-angle glaucoma in conjunction with miotics, refraction, ophthalmoscopic examination and before intraocular surgery.

Contraindications Hypersensitivity to any of these agents, narrow-angle glaucoma, patients with long standing insulin-dependent diabetes, hypertensive patients receiving reserpine or guanethedine, aneurysm, cardiac diseases, debilitated and elderly patients and patients with IOL implantation.

Dosage For pupillary dilatation commercial concentrations of 2.5 percent and 10 percent (in 2.5 ml and 15 ml packs) ophthalmic solutions are available. Maximum dilatation occurs in 45 to 60 minutes depending upon the concentration used and number of drops instilled. The pupil size usually returns to predrug levels within 4 to 6 hours. Since phenylephrine has little or no effect on the ciliary muscle, mydriasis occurs without cycloplegia.

Phenylephrine 1 percent solution can be used in diagnosis of Horner syndrome. Significantly mydriasis can occur in the eye with a postganglionic lesion as compared to normal innervation.

The mydriatic response may be affected in cases of injury to corneal epithelium (corneal abrasions and trauma). Concentration as small as 0.125 percent present in decongestant solution has been reported to cause mydriasis if the corneal epithelium is damaged. In general 2.5 percent topical concentration is used for routine dilatation, specially in children and elderly patients because 10 percent concentration has clinical ocular and systemic side effects.

For diagnostic purpose usual dosage is 1 drop of 2.5 percent solution in each eye followed by one drop more in 5 to 10 minutes. Sufficient mydriasis is produced in 15 to 30 minutes and effect lasts for 4 to 6 hours. For pathological condition usual dosage is 1 drop of 2.5 percent or 10 percent solution (depending upon the condition) three times a day till the desired result is obtained.

Topical phenylephrine can be used alone or in combination with other mydriatic/cycloplegic agents in diagnostic procedures and pathological conditions of the eye.

Adverse reactions On topical use it may cause transient stinging on initial instillation, blurring of vision and rarely maculopathy with a central scotoma results from use in aphakic patients.

Prompt reversal generally follows discontinuation.

Phenylephrine may cause rebound miosis and decreased mydriatic response to therapy in older persons.

Systemic side effects include CVS effects like palpitation, tachycardia, extrasystole, cardiac arrhythmia, hypertension, headache and browache but usually diminishes as the treatment is continued.

Other effects include reflex bradycardia, pulmonary embolism, myocardial infarction, stroke and death associated with cardiac reactions. Sometimes 10 percent phenylephrine on conjunctival instillation may cause significant elevation of blood pressure. Exercise caution with elderly patients and children and carefully monitor the blood pressure in such cases.

Hydroxyamphetamine

Hydroxyamphetamine is an indirect acting adrenergic agonist. Its pharmacological action is primarily due to release of norepinephrine from postganglionic adrenergic nerve terminals. It has very little effect on accommodation.

Indications To dilate the pupil for diagnostic procedure and ophthalmoscopic examination of the eye.

Dosage Hydroxyamphetamine is available as 1 percent topical solution (15 ml pack). It has mydriatic effect comparable to 2.5 percent phenylephrine. Maximum pupillary dilatation occurs in 25 to 40 minutes and effect lasts for 4 to 6 hours.

Since the drug stimulates the release of norepinephrine from adrenergic nerve terminals, its mydriatic effect depends on the integrity of the adrenergic innervation to the pupil. A pupil with postganglionic sympathetic lesion will fail to dilate.

Hydroxyamphetamine can be used to differentiate clinically postganglionic Horner’s syndrome from one that is central or preganglionic. Hydroxyamphetamine is a slightly weaker mydriatic in young children and infants because the adrenergic innervation to the iris is not yet fully developed in this age group. Adverse effects are similar to those reported with phenylephrine.

Cholinergic Antagonist as Mydriatic Agents

Cholinergic antagonist specially tropicamide differs from phenylephrine and hydroxyamphetamine in its mechanism of action. Tropicamide blocks the effects of acetylcholine released from cholinergic nerve endings at the iris sphincter and ciliary muscle. The drug, therefore, causes mydriasis and cycloplegia. Compared to other cycloplegics, the accommodative effect of tropicamide is less pronounced and of shorter duration.

Dosage Following topical instillation of 0.5 percent or 1 percent ophthalmic preparation. Mydriasis occurs within 20 to 30 minutes and effect lasts for 6 to 8 hours. The advantage of tropicamide over adrenergic mydriatics is that mydriasis with it is more pronounced

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and bright illumination has no significant effect on pupil size. The mydriatic effect appears independently of iris pigmentation.

Adverse reactions to tropicamide are quite rare. Since it is devoid of vasopressor action, it is safe for use in patients with cardiac disease and hypertension. Due to its relatively faster onset, short duration and intensity of mydriatic action, tropicamide is presently the drug of choice for pupil dilatation. For clinical situations where maximum pupillary dilatation is desirable, tropicamide is combined with phenylephrine or hydroxyamphetamine. Various commercial combinations are available. The details are given at the end of this chapter.

Cycloplegic Mydriatics

Cycloplegic mydriatics are commonly used for both objective and subjective refractive procedures.

In different pathological conditions of the eye as treatment, specially strabismus in children (esotropia), uveitis (anterior and posterior uveitis) these agents are commonly used.

Parasympatholytic agents are commonly used as cycloplegic mydriatics.

Mechanism of Action

Anticholinergic agents block the responses of the sphincter muscle of the iris and the muscles of the ciliary body to cholinergic stimulation producing pupillary dilatation (mydriasis) and paralysis of accommodation (cycloplegia).

Indications

For cycloplegic refraction and for dilatation of pupil in the inflammatory conditions of the iris and uveal tract.

Contraindications

Narrow angle glaucoma, sensitivity to belladona alkaloids or any component. In elderly patients specially with atropine where undiagnosed glaucoma or extensive pressure in the eye may be present.

Precautions

•Avoid excessive systemic absorption by compressing the lacrimal sac by digital pressure for 1 to 2 minutes after instillation.

•Permanent mydriasis may occur in patients with keratoconus.

•Use with caution longer acting agents (atropine and scopolamine) and they may cause posterior synechiae formation when treating anterior segment inflammation.

•Acute hypersensitivity reaction, discontinue use and have 1:1000 epinephrine solution available.

•Sulfite sensitivity.

•Avoid potentially hazardous tasks (observe caution while driving or performing other tasks requiring alertness).

•Do not exceed recommended dosages.

•Excessive use in children and suspectible cases should be avoided.

Adverse Reactions of Parasympatholytic Agents

On topical use adverse effects reported are increased IOP, transient stinging and burning sensation, allergic lid reactions, hyperemia, follicular conjunctivitis vascular congestion, edema, exudate, photophobia and eczematoid dermatitis.

Systemic adverse effects include systemic atropine toxicity manifested by flushing and dryness of the skin, blurred vision, photophobia with or without corneal staining, dryness of mouth and nose, anhydrosis, fever, rapid pulse, bladder distention, hallucinosis, loss of neuromuscular coordination. Severe reactions are manifested by hypotension with progressive respiratory depression, coma, medullary paralysis and death.

Other adverse effects reported are cardiac dysrhythmias especially in patients undergoing surgery for glaucoma. Headache, parasympathetic stimulation, allergic reactions and toxic manifestations of anticholinergic drugs.

In addition, use of cyclopentolate and tropicamide has been associated with psychotic reactions and behavioral disturbances in children. CNS disturbances like ataxia, incoherent speech, restlessness, seizures, disorientation to time and place and failure to recognize peoples.

Overdosage

When symptoms of atropine toxicity develop (see adverse reactions) administer parenteral physostigmine.

Various parasympatholytic agents used in ophthalmology as cycloplegic mydriatics (Table 15.1) are:

•Atropine

•Homatropine

•Scopolamine

•Cyclopentolate

•Tropicamide.

Individual drug monograph is as follows:

TABLE 15.1 Cycloplegic mydriatics

Atropine Sulfate

Atropine sulfate is a potent parasympatholytic agent for use in producing cycloplegia and mydriasis.

It is the strongest mydriatic for common use in ophthalmology.

It completely paralyzes the sphincter pupillae and ciliary muscle. It takes considerable time to cause complete paralysis.

It is an alkaloid used in water soluble form (atropine sulfate).

Indication Atropine sulfate is used both for its cycloplegic and mydriatic effects for cycloplegic refraction or for pupil dilatation in acute inflammatory conditions of the iris and uveal tract. For cycloplegic refraction its use is on decline due to the availability of faster acting, short duration parasympatholytic agents.

Dosage Atropine sulfate is available as topical ophthalmic solution in concentration of 0.5 percent, 1 percent, 2 percent and 3 percent. Atropine ointment is available in 0.5 percent and 1 percent concentrations.

A single drop of 1 percent atropine solution results in maximal mydriasis in about three hours and effect of single dose lasts for 3 to 7 days.

•For uveitis treatment usual dosage is to instill 1 to 2 drops of 1 percent solution into the eyes four times daily while in children recommended dosage is to instill 1 to 2 drops of 0.5 percent solution three times a day.

•For refraction—instill one drop of 1 percent solution into the eye twice a day 1 to 2 days prior to examination. While in children recommended dosage is 1 to 2 drops of 0.5 percent solution twice daily 1 to 3 days before the examination and 1 hour before examination.

Ophthalmologists consider atropine as first drug of choice for the first refraction in all children under the age of 7 years or when there is risk of convergent strabismus. It may also be used as type of occlusion in amblyopia, latent nystagmus and in difficult cases of accommodative spasms.

Atropine is drug of choice in severe anterior segment inflammation reducing the risk of posterior synechiae.

Adverse reactions Generalized adverse reactions of parasympatholytic agents are already discussed in this chapter. As atropine has potential local and systemic side effects, it is necessary to discuss these effects separately.

Ocular adverse effects Atropine may cause local irritation, accommodative spasm, anterior movement of lens-iris-diaphragm, breakdown of blood-aqueous barrier, decreased anterior chamber depth, drug-induced cicatrizing conjunctivitis, hyperemia, corneal toxicity, increased intraocular pressure, cataract formation, allergic blepharoconjunctivitis, twitching of orbicularis oculi, iris cyst, miosis, increased peripheral vitreal traction.

Systemic effects Dose related side effects are depicted in Table 15.2.

>10 mg (20 drops or more of 1% solution) – Above side effect and ataxia, hyperexcitability

–Hallucination

–Coma

–Convulsion

–Death

Homatropine

Homatropine is semisynthetic alkaloid prepared from atropine. It is used in its water soluble form—homatropine hydrobromide.

Indications Homatropine is moderately long-acting mydriatic and cycloplegic for refraction and in treatment of inflammatory conditions of the uveal tract, for preoperative and postoperative states when mydriasis is required and as an optical aid in certain cases of axial lens opacities.

Dosage Homatropine is available as 2 percent and 5 percent ophthalmic solution.

For refraction instill 1 to 2 drops of 2 percent solution into the eyes and repeat it 5 to 10 minutes if necessary.

For uveitis instill 1 to 2 drops of 2 percent solution into the eyes every 3 to 4 hour interval.

It acts more quickly than atropine, mydriasis being usually complete within 40 minutes and cycloplegia after one hour of instillation. The duration of action is shorter than atropine and recovery occurs in about 24 hours.

Adverse effects have already been covered in general monograph of parasympatholytic agents.

Scopolamine

Scopolamine is used in its water soluble form of scopolamine hydrobromide.

Indications Scopolamine is an anticholinergic agent for use in producing cycloplegia and mydriasis, for preoperative and postoperative states in the treatment of iridocyclitis. Dosage Scopolamine is available as 0.25 percent ophthalmic solution. Usual dosage for refraction is to instill 1 to 2 drops into the eye 1 hour before refraction.

For uveitis, instill 1 to 2 drops four times daily into the affected eyes.

Its mydriatic effect starts in 20 to 30 minutes and cycloplegic effect appears in 30 to 60 minutes and duration of effect lasts for 3 to 7 days.

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Cyclopentolate HCl

Cyclopentolate hydrochloride is a synthetic mydriatic and cycloplegic agent. It is very effective and short-acting.

Indications Cyclopentolate hydrochloride is used for mydriasis and cycloplegia in diagnostic procedures.

Dosage Cyclopentolate is available as 0.5, 1 and 2 percent ophthalmic solution. Maximal mydriasis occurs in 30 minutes and cycloplegia is usually complete in 40

minutes.

To ensure complete cycloplegia two applications of Cyclopentolate HCl are used at 10 minutes interval.

Recovery of accommodation usually occurs in 8 to 24 hours.

Recommended dosage in adults—instill one drop of 1 percent solution, repeat in 5 to 10 minutes. Although complete recovery occurs in 24 hours time, yet 1 to 2 drops of 1 percent or 2 percent pilocarpine reduces recovery time to 3 to 6 hours in most eyes.

In children usual dosage is to instill 1 drop of 0.5 percent, 1 percent or 2 percent solution in each eye followed 5 minutes later by second application. Observe patient closely for at least 30 minutes following instillation.

Tropicamide

Tropicamide is another rapidly acting mydriatic and cycloplegic agent and acts faster than Cyclopentolate (Short-acting anticholinergic agent).

It blocks the parasympathetic fibers and causes relaxation of sphincter pupillae muscle of the iris producing mydriasis.

Indications For mydriasis and cycloplegia for diagnostic purposes, when short-acting mydriatic is needed for some preoperative and postoperative states.

It prevents constriction of pupil caused by intense light stimulation during indirect ophthalmoscopy or retinal photography.

Dosage Tropicamide is available as 0.5 percent and 1 percent ophthalmic solutions. Recommended dosage for refraction is to instill 1 to 2 drops of 1 percent solution into

the eyes, repeat after 5 minutes an additional drop to prolong mydriatic effect.

For fundus examination, instill 1 to 2 drops of 0.5 percent solution 15 to 20 minutes prior to examination.

On account of its short latency, brief duration and effective mydriasis, it is perhaps the best mydriatic for the usual fundus examination.

Due to shorter duration of action, it is used as provocative test for acute glaucoma though under strictly controlled conditions.

It is used alone or in combination of sympathomimetic agent (phenylephrine) to produce much better response and mydriatic effect persists to facilitate ocular examination.

Some other drugs of this group were previously used for mydriatic and cycloplegic effect but now not in use.

1.Duboisine (0.1–1.0% drops)

2.Lachesine or E3 (0.5 drops)

TABLE 15.3 Relative efficiency of cycloplegics

Drug % Efficiency

Mydriatic Combinations

Phenylephrine is commonly used with tropicamide, cyclopentolate or scopolamine to induce mydriasis which is greater than of either drug alone.

Phenylephrine 5 percent and Cyclopentolate HCl 1 percent Instill 1 drop into each eye every 5 to 10 minutes not to exceed three times.

Phenylephrine 10 percent and Scopolamine 0.3 percent For mydriasis, cycloplegia and to break posterior synechiae in iritis.

Dosage For mydriasis 1 to 2 drops into the eye and repeat in 5 minutes if necessary. Postoperatively 1 to 2 drops into the eyes 3 to 4 times daily.

Phenylephrine 5 percent with tropicamide 0.8 percent

•For short acting mydriasis in refraction and in preand postoperative states.

•For refraction instill 1 to 2 drops and repeat at 5 minutes interval, if necessary.

•For postoperative stage instill 1 to 2 drops three times a day.

Cyclopentolate HCl 1 percent with Dexamethasone sodium phosphate 0.1 percent

• For postoperative inflammation where mydriatic and inflammatory therapy is simultaneously required.

Dosage Instill 1 to 2 drops into the affected eyes three times a day.

Atropine Sulfate 1 percent solution with Dexamethasone sodium phosphate 0.1 percent

For postoperative inflammation and anterior and posterior uveitis where mydriatic and inflammatory therapies are required in addition also.

Dosage Instill 1 to 2 drops into the affected eyes three a day.

Phenylephrine (5%) and tropicamide (0.8%) combination is commonly used in ophthalmology today. The major advantage of this combination is that it produces quick mydriasis and mydriatic effect persists to facilitate ocular examination.

Indications This preparation is mainly indicated for

•Ophthalmoscopic examination

•Slit lamp examination

•Retinal photography

•Prior to ocular surgery and other diagnostic procedures.

It is also used

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•As an adjunct in the treatment of anterior uveitis

•In the management of anterior segment burns (to dilate the pupil and prevent iris adhesions to the lens)

•In cycloplegic refraction

•For the management of iridocyclitis associated with stromal keratitis

•For the management of uveal inflammation associated with fungal keratitis.

Dosage This combination is available as topical ophthalmic solution (in 5 ml pack). For ophthalmological examinations, 1 to 2 drops in the eye 15 to 30 minutes prior to the procedure are advised. For other indications frequency should be as per direction of ophthalmologists.

This preparation is contraindicated in patients suffering from closed angle glaucoma and hypersensitivity to any ingredient of this formulation.

Adverse reactions On topical application there may be transient burning or stinging sensation and lacrimation. Blurred vision, photophobia and allergic reactions may occur.