Optometrists are well-acquainted with the two opposing muscles in the iris, the sphincter and the dilator, as we witness their effects daily in clinical practice. Pupil constriction (miosis) can either be stimulated by contraction of the iris sphincter or by relaxation of the iris dilator. On the other hand, pupil dilation (mydriasis) can either be stimulated by contraction of the iris dilator or by relaxation of the iris sphincter. Miotic and mydriatic drops work by acting on these different muscles of the iris. The drops are able to control pupil size by targeting two parts of the autonomic nervous system: the sympathetic and parasympathetic systems. Let’s review their function and clinical role to better understand their present uses and why some of these agents are undergoing re-evaulation for potential new ones. Behind the Scenes The sympathetic pathway, mainly responsible for pupil mydriasis, involves a three-neuron pathway.1,2 The first neuron begins in the hypothalamus and descends through the midbrain to synapse onto a specific area of the spinal cord, known as the ciliospinal center of Budge. This synapse is located between the C8 and T2 vertebrae. The second neuron, which is the preganglionic neuron, exits the spinal cord, ascends through the thorax and synapses near the apex of the lung into the superior cervical ganglion. The third postganglionic neuron travels to the cavernous sinus and enters the orbit through the short and long ciliary nerves, synapsing to the iris dilator.1,2 Contrarily, the parasympathetic pathway is mainly responsible for pupil miosis.1,3 Pupil constriction starts when light enters the retina and activates the retinal ganglion cells—the beginning of the afferent arm—which then transmit their impulses into the optic nerve. This stimulus travels to the optic chiasm, through the optic tract and eventually reaches the pretectal nucleus. The impulses from the pretectal nucleus begin the efferent arm, which projects to the Edinger-Westphal nucleus. The Edinger-Westphal nucleus gives rise to preganglionic fibers, which then synapse with postganglionic neurons in the ciliary ganglion. Postganglionic neurons leave the ciliary ganglion to innervate the iris sphincter.1,3 Tropicamide has a strong mydriatic effect. Tropicamide has a strong mydriatic effect. Click image to enlarge. Behind the Scenes The sympathetic pathway, mainly responsible for pupil mydriasis, involves a three-neuron pathway.1,2 The first neuron begins in the hypothalamus and descends through the midbrain to synapse onto a specific area of the spinal cord, known as the ciliospinal center of Budge. This synapse is located between the C8 and T2 vertebrae. The second neuron, which is the preganglionic neuron, exits the spinal cord, ascends through the thorax and synapses near the apex of the lung into the superior cervical ganglion. The third postganglionic neuron travels to the cavernous sinus and enters the orbit through the short and long ciliary n

1. MIOTICS & MYDRIATICS
Presenter : Dr. Shamika
Moderator: Dr. Arun Kumar
Date: 05/02/2016

2. Muscles of the iris:
•DILATOR PUPILLAE
•Dual nerve supply.
•Sympathetic α1
adrenergic are
stimulatory while
parasympathetic are
inhibitory.
•SPHINCTER PUPILLAE
•Dual nerve supply.
•Parasympathetic
muscarinic are
stimulatory while
sympathetic are
inhibitory.

3. Miotics
Parasympathomimetic drugs
Choliergic drugs.
Classified as-
1. Directly acting or agonists. Eg-acetylcholine, bethanechol, pilocarpine.
2. Indirectly acting or cholinesterase inhibitors.
a. Reversible. Eg- physostigmine, neostigmine, edrophonium.
b. Irreversible. Eg- ecothiophate iodide, demecarium, diisopropylfluro phosphate.
3. Dual action: having bothmuscarinic and weak cholinesterase action. Eg-
carbachol.
4. Reactivation of acetylcholinesterase: pralidoxime.

4. • Five types of muscarinic receptors:
• The M1 receptors are located in the nervous system.
• The M2 receptors are located in the heart, and slow the heart
rate and force of contraction.
• The M3 receptors are located at the endothelial cells of blood vessels
and cause vasodilatation, lungs causing bronchoconstriction the
smooth muscles of the GIT to increase intestinal motility and dilating
sphincters, glands to stimulate secretion in salivary glands, detrusor
muscle and urothelium of the bladder, causing contraction. They are
present in the ciliary muscle and the iris.
• The M4 receptors: Postganglionic cholinergic nerves, possible CNS
effects
• The M5 receptors: Possible effects on the CNS

5. Stimulation of the M3 receptors in the eye causes-
1. Contraction of the pupil (miosis) and alters the relationship
of the iris with thee lens behind and the anterior chamber
angle in front.
2. They contract the longitudinal fibres of the ciliary body and
cause opening of the trabecular meshwork and increase
the aqueous outflow.
3. They cause contraction of the circular muscles of the ciliary
body thus causing the zonules to relax and allow the lens
to assume a more spherical shape (accommodation).

6. Pilocarpine hydrochloride:
• It is a parasympathomimetic alkaloid obtained
from the leaves of tropical South American
shrubs from the genus Pilocarpus. It is a non-
selective muscarinic receptor agonist.
• It was introduced in 1877 for the treatment of
glaucoma.
• When applied topically it is largely degraded
in the cornea. Only 3% enters the aqueous.
• It is available in 0.12%, 0.25%, 0.5%, 1%, 2%,
3% ,4%, 6%.

7. •Pilocarpine ocular therapeutic system (ocusert)
is available as ocusert P-40 or P-20 or
incorporated into soft contact lenses.
•Is also available in a polymer vehicle as a gel
that prolongs the duration of action.
•The ocusert releases 3 times the dose for 1 hour
and then declines to required value over 6
hours.
•Are to be placed in the cul de sac before
sleeping, so that the induced myopia wanes
away by morning.

8. Uses:
1. It causes complete miosis on intracameral administration.
Used in cataract sx after lens extraction, in penetrating
keratoplasty, iridectomy, etc.
2. 0.12% is used diagnostically to confirm Adie’s tonic pupil.
In this condition there is defective parasympathetic
innervation to the iris and ciliary body due to post
ganglionic denervation. The affected muscles exhibit
hypersensitivity to pilocarpine and hence contract, while
normal iris does not react to this low concentration.
3. 0.25% to 6% are used in the management of primary open
angle glaucoma. It is contraindicated in acute angle
closure glaucoma because it cause anterior movement of
lens iris diaphragm.

9. 4. As it causes increase in tear secretion and punctal
stenosis as side effects, it is used in aqueous tear
deficiency (ATD) dry eye. Due to increased
salivation and lacrymal secretion it is used in
Sjgrens’s syndrome and also for dry eye and
xerostomia as an effect of radiation therapy for
head and neck cancer.
5. Used to differentiate pharmacological mydriasis
from neurological mydriasis. In pharmacological as
the receptors are saturated the pupil will remain
dilated while in third nerve palsy or Adie’s tonic
pupil it will constrict even with very dilute
solution.

10. 6. Used to reduce glare in patients with intra
ocular lens Implantation.
7. Pilocarpine is used to stimulate sweat glands
in a sweat test to measure the concentration
of chloride and sodium that is excreted in
sweat. It is used to diagnose cystic fibrosis.

11. Adverse effects:
1. Contraction of the ciliary body can cause traction on the pars
plana as well causing retinal tear or rhegmatogenous retinal
detachment.
2. Catarctogenesis.
3. Drug induced contraction of the ciliary body causes increased
convexity of the lens and shifts the lens forward. Hence causes
induced myopia. This causes brow ache.
4. Reduced vision during night time due to miosis. Reduced field
of vision.
5. Higher concentration use causes miotic iris cysts
6. Increased lacrimal secretion and punctal stenosis can cause
epiphora.
7. Increased bleeding during surgery.

12. 8. It causes break down of the blood aqueous barrier hence
can cause severe fibrinous iridocyclitis post operative.
Hence it is contraindicated in uveitic glaucoma.
9. Posterior synechiae formation.
10. It is known to cause idiosyncratic reaction, allergic
reaction, pseudopemphigoid.
11. Systemic- salivation, diarrhoea, urinary urgency,
vomiting, bronchospasm, bradycardia, diaphoresis,
flushing.
12. Succinyl choline should be avoided in patients who have
used these drugs recently.

13. Acetylcholine Carbachol
• Used only intracamerally as
it is not active if used
topically.
• Available as a powder. Fresh
solution has to be prepared.
When given intracamerally
it causes miosis in seconds.
• Rapidly degraded by
cholinesterases in aqueous.
Hence v short acting.
• It is 100 times effective and
longer acting than
acetylcholine.
• Lesser fluctuations in IOP.
Effect last upto 8 hours.
• ADR- corneal clouding,
bullous keratopathy, iritis,
injection, ciliary spasm,
retinal detachment.
• Topical- 0.75%, 1.5%, 2.5%,
3%. 3 times a day
• Intracameral- 0.01%

14. Physostigmine Demecarium
•Acetylcholinesterase
inhibitor.
•Same actions, uses.
•Used in patients who
fail to respond to
directly acting
cholinergic agents.
•0.25-0.5% up to 4 times
a day. Eye ointment also
available.
•Same as physostigmine.
•Also used for
accommodative
esotropia. 0.125% once
a day for 3-4 weeks.
Miosis may interfere.
•Prolonged action. Twice
daily usage. Severe ADR.
•0.125% twice a day.
•Avoid overdosing.

15. Ecothiophate
• Depresses plasma & erythrocyte cholinesterase.
• Used in subacute or chronic angle closure glaucoma.
• Topical solution is prepared by reconstituting powder
form. Concentrations available are 0.03, 0.06, 0.125 and
0.25%.
• Tolerance may develop on chronic use.
• As it is an insecticide it is also used for lice infestations of
the eye lashes.

16. Mydriatics
• Mydriatics are agents who dilate the pupil and
cycloplegics are agents which cause paralysis off
the ciliary body.
• Two classes of mydriatics are available-
1. Adrenergic agonists- adrenaline, cocaine,
phenylephrine, hydroxyamphetamine.
They cause pupillary dilatation, increase in aqueous
outflow, decreased aqueous formation, and relaxation
of ciliary muscles.
1. Cholinergic antagonists- tropicamide.
Causes mydriasis and cycloplegia.

18. Adrenaline (epinephrine) Cocaine
• Causes mydriasis.
• 1:1000 solution used.
Repeated in 5 minutes.
• Used for open angle
glaucoma.
• Can be used with procaine
and atropine in severe
iritis.
• Alkaloid
• 2 and 4% solution.
• Toxic to corneal epithelium
(hence increased
penetration).
• Inhibits the action of
amine oxidases and hence
reduces the uptake of NE.
• Used to diagnose Horner’s
syndrome.

19. Horner’s syndrome.
It is caused due to a lesion in the oculosympathetic
pathway.
Characterised by ipsilateral miosis, ptosis and
anhidrosis.
The light reflex is normal in these patients but the
pupil is slow to redilate in dim light.

20. It can be tested pharmacologically as—
Step 1: Instill 2 drops of 4% cocaine in both eyes.
It inhibits reuptake of nor epinephrine from the post
ganglionic segment. Hence causes mydriasis. But in
Horner’s there is no NE. Hence no dilatation.
Post cocaine anisocoria of 1mm is diagnostic.
Apraclonidine has weak α1 agonistic action. In normal
eyes it has little effect on pupil. But in Horner’s
syndrome there is supersensitivity and the pupil
dilates.

21. •Step 2: once diagnosis is established,
hydroxyamphetamine is used to localise the
lesion.
•Normal pupil dilates with
hydroxyamphetamine. If the Horner’s pupil
does not dilate means lesion is in the
preganglionic segment. But if it does dilate
lesion is in the preganglionic segment.

22. Phenylephrine hydrochloride
•Causes pupil dilatation and conjunctival
vasoconstriction causing blanching.
•Action can be reversed by thymoxamine 0.1%.
•2.5 and 10% concentrations. 2.5% used most
commonly.
•Sufficient mydriasis occurs in 15-30 mins,
maximum dilation in 45-60 mins and remains for 4-
6 hours.
•Since sphincter pupillae muscles are stronger than
dilator, mydriasis caused by phenylephrine is
largely overcome by light reflex.

23. Phenylephrine hydrochloride
Uses
• Used mainly for pupil dilation for diagnostic purposes
and in pathological conditions like uveitis, for
cycloplegic refraction, before intraocular surgery and
in conjunction with miotics.
• As an ocular decongestant.
• Used to diagnose Horner’s syndrome. In Horner’s
syndrome, phenylephrine 1% solution administered
causes mydriasis more than that in the normal eye,
because of denervation hypersensitivity.

24. Adverse effects
•Ocular- transient
stinging, blurring, rarely
maculopathy in aphakic
patients.
•Systemic-
• Palpitations.
• Tachycardia.
• Extrasystoles.
• Arrhythmias.
• Hypertension.
• Headache.
• Browache.
• Reflex bradycardia
• Stroke.
• Myocardial infarction.
10% solution contains 5mg
of drug per drop. Systemic
dose for hypotension is 50-
100 micro gram.

25. Contraindicated in-
• Narrow angle glaucoma.
• Hypertensives.
• Type 1 diabetes mellitus.
• Aneurysms.
• Cardiac diseases.
• Old debilitated patients
• Patients on reserpine, TCAs MAO inhibitors or cocaine.
• Infants. As it increases BP (dose per unit weight is high)

26. Hydroxyamphetamine hydrobromide
•Indirect acting adrenergic agent.
•It releases nor- epinephrine from post
ganglionic nerves.
•Minimal cycloplegia.
•1% concentration equivalent to 2.5%
phenylephrine.
•25-40 minutes for max dilatation. Lasts 4-6
hours.

27. Uses-
•To dilate the pupil for ocular examination.
•To differentiate post ganglionic Horner’s
syndrome from pre ganglionic Horner’s
syndrome. Post ganglionic lesions fail to dilate.

28. Tropicamide
•Blocks the effect of acetyl choline released.
•Causes mydriasis and cycloplegia both.
•0.5 or 1% acts within 20-30 minutes and
effect lasts for 6-8 hours.
•Mydriasis is more pronounced. It prevents
pupil constriction in response to indirect
ophthalmoscopy and retinal photography.
•Independent of iris pigmentation.

29. Uses and Adverse reactions
•Since it has no vasopressor action it can be
used safely in cardiac patients.
•It is the first choice of mydriatic because it is
rapid acting, short acting, and strong intensity
of action.
•Commonly used as a combination with
phenylephrine or hydroxyamphetamine.

30. Mydriatics and cycloplegics
•Atropine, homatropine, scopolamine and
cyclopentolate are cycloplegics that are used in
uveitis or acute anterior segment inflammation to
reduce the formation of posterior synechiae.
•They also reduce the permeability of blood aqueous
barrier and help to reduce inflammation apart from
causing cycloplegia.
•They can be used as occlusion therapy for
amblyopia.

31.  Thank you 