Myth Meets Molecules · Mydriatics & Miotics

1

Anatomy of the Eye — Foundations

The two iris muscles, ciliary muscle, and the visual pathway

1.1The Two Muscles of the Iris

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Muscle	Fibre Type	Receptor & System	Contraction Effect
Sphincter Pupillae	Circular (ring-shaped around pupil)	M3 Muscarinic (Parasympathetic) — activated by acetylcholine	Pupil gets SMALLER → MIOSIS
Dilator Pupillae	Radial (spoke-like, pupil outward)	α1 Adrenergic (Sympathetic) — activated by noradrenaline/adrenaline	Pupil gets BIGGER → MYDRIASIS
Ciliary Muscle	Smooth muscle around the lens	M3 Muscarinic (Parasympathetic)	Contraction → lens becomes CONVEX → near vision (accommodation). Paralysis → cycloplegia

⚡ Foundation Rule: If parasympathetic wins → MIOSIS. If sympathetic wins → MYDRIASIS. ALWAYS think in terms of which system is activated or blocked.

1.2Ciliary Muscle & Accommodation

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When ciliary muscle CONTRACTS (parasympathetic, M3): Suspensory ligaments RELAX → Lens becomes more CONVEX → focuses on NEAR objects = Accommodation
When ciliary muscle is PARALYSED (anticholinergic drugs): Lens cannot change shape → Eye fixed for DISTANT vision → CYCLOPLEGIA — near vision blurred, cannot read fine print

⚡ Cycloplegia: Paralysis of the ciliary muscle = inability to accommodate = inability to read fine print. Drugs causing this = cycloplegics. Examples: Atropine, Tropicamide.

1.3Visual Pathway — Brief Overview

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Light → Cornea → Lens → Retina (photoreceptors) → Optic nerve → Optic chiasm (nasal fibres cross) → Optic tract → Lateral Geniculate Nucleus (LGN) in thalamus → Primary Visual Cortex → Secondary Visual Cortex
Right visual field → Left side of each eye → Left optic tract → Left visual cortex
Left visual field → Right visual cortex
Fibres cross at the optic chiasm
Edinger-Westphal nucleus: part of the parasympathetic oculomotor nucleus in the brainstem — stimulated by IV morphine → produces pinpoint pupils

2

Definitions — Miotics and Mydriatics

Active vs passive mydriasis — the critical distinction for the exam

Term	Definition & Mechanism
MIOTICS	Drugs that CONSTRICT the pupil (cause MIOSIS). Mechanism: Contraction of sphincter pupillae via M3 muscarinic (parasympathetic) activation.
MYDRIATICS	Drugs that DILATE the pupil (cause MYDRIASIS). Two mechanisms: (1) Active — α1 stimulation of dilator pupillae. (2) Passive — M3 blockade of sphincter pupillae.

2.1Active vs Passive Mydriasis

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Type	Mechanism	Drugs	Light Reflex
Active Mydriasis	Sympathomimetics stimulate α1 adrenergic receptors on dilator pupillae → muscle CONTRACTS → pupil dilates	Phenylephrine, Ephedrine, Adrenaline	PRESERVED — sphincter intact
Passive Mydriasis	Anticholinergics block M3 receptors on sphincter pupillae → muscle CANNOT CONTRACT → pupil dilates passively	Atropine, Tropicamide, Hyoscine	ABOLISHED — sphincter's neural drive is blocked

⚡ Critical Exam Question: Light reflex is LOST with anticholinergics (Atropine). Light reflex is PRESERVED with sympathomimetics (Phenylephrine). Tested every year.

3

Classification of Miotics & Mydriatics

All drugs with mechanism, concentration, and key features

Miotics

Drug (Concentration)	Mechanism	Effects & Uses
Pilocarpine (0.5–4%)	Direct M3 agonist. Naturally occurring alkaloid from Pilocarpus plant.	Miosis in 10 min, lasts ~4 hrs. Lowers IOP. Used in glaucoma (both types). Improves near vision, blurs distant.
Physostigmine (1–2%)	Reversible anticholinesterase (indirect). Inhibits AChE → ACh builds up → stimulates M3.	Miosis + ciliary spasm. Also used in glaucoma. Absorbed locally to produce miosis.
Carbachol	Direct cholinergic agonist (both muscarinic + nicotinic).	Miosis and decreased IOP.

⚡ Pilocarpine vs Physostigmine: Pilocarpine is DIRECT (acts on M3 receptor). Physostigmine is INDIRECT (inhibits the enzyme that breaks down ACh).

Mydriatics — A. Anticholinergic (Passive Mydriasis + Cycloplegia)

Drug	Mechanism	Duration	Key Clinical Notes
Atropine (1%)	Competitive M3 antagonist. Blocks sphincter pupillae AND ciliary muscle.	7–14 days	Mydriasis + CYCLOPLEGIA. Light reflex ABOLISHED. Contraindicated in glaucoma. Raises IOP.
Homatropine (0.5–2%)	Shorter-acting M3 blocker.	24–48 hours	Mydriasis + cycloplegia. Used for fundoscopy.
Tropicamide (1%)	Short-acting antimuscarinic. M3 blocker.	4–8 hours	PREFERRED for routine fundoscopy/refraction. Onset 15–30 min. Avoid soft contact lenses after use.
Hyoscine / Scopolamine	Competitive M1 antagonist. Anticholinergic alkaloid.	~6 hours	Mydriasis + cycloplegia. Reduces salivation, increases HR. Max effect at ~3 hours. Motion sickness.
Cyclopentolate	Anticholinergic.	Shorter than atropine	Mydriasis + cycloplegia. Used for refraction testing.

Mydriatics — B. Sympathomimetic (Active Mydriasis — NO Cycloplegia)

Drug	Mechanism	Key Clinical Notes
Phenylephrine (2.5–10%)	Direct α1 adrenergic agonist. Stimulates dilator pupillae.	Mydriasis WITHOUT cycloplegia. Light reflex PRESERVED. Used for fundoscopy.
Ephedrine (5%)	Indirect sympathomimetic. Releases stored noradrenaline.	Mydriasis. Light AND corneal reflexes preserved.
Adrenaline (0.1%)	Direct α1 and β2 agonist.	Mydriasis. Also reduces IOP by decreasing aqueous humor production (β2 on ciliary epithelium).
Cocaine (1%)	Local anaesthetic + indirect sympathomimetic (blocks NA reuptake → more NA at α1).	Mydriasis + LOSS OF CORNEAL REFLEX (local anaesthetic). Light reflex preserved. UNIQUE profile.

⚡ Cocaine is UNIQUE: ONLY drug that causes both MYDRIASIS (NA reuptake block) AND loss of CORNEAL REFLEX (local anaesthetic). A favourite exam question.

4

The CAL Experiment — Effect of Drugs on Rabbit Eye

Procedure, parameters, precautions, and expected results

4.1Animal Model, Equipment & Drugs

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Animal: Rabbit (1.5–2.5 kg) — large eye, easy to handle, sensitive to topical drugs
Pupillometer: scale with round holes: 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm — to measure pupil diameter
Torch: to test light reflex
Cotton tip: to test corneal reflex at corneoscleral junction (brought from the SIDE)
Volume instilled: 40–60 μl only (2–3 drops)

Drugs Used

Drug Type	Examples
Miotics	Pilocarpine 0.5–4%, Physostigmine 1–2%
Sympathomimetic Mydriatics	Adrenaline 0.1%, Phenylephrine 2.5–10%, Ephedrine 5%
Anticholinergic Mydriatics	Atropine 1%, Homatropine 0.5%
Special (Local Anaesthetic)	Cocaine 1%
Control	Normal Saline

4.2Procedure — Step by Step

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1

Weigh and mark the rabbits. Select 3 rabbits: one each for pupil, corneal, and light reflex testing.

2

Restrain in restrainer with head protruding. Acclimatise for 5 minutes to reduce stress-related pupil changes.

3

Mark one eye as Test Eye (TE) and the other as Control Eye (CE). Trim eyelashes of both eyes with scissors.

4

Instil normal saline into BOTH eyes to clean and establish baseline (control) reading.

5

Instil test drug into the TEST EYE ONLY (2–3 drops; 40–60 μl). Control eye remains untreated.

6

After 5 minutes, measure and record all four parameters in both eyes.

⚡ Key Precautions: Experiment performed in DIM LIGHT (strong light constricts pupil and confounds results). Do NOT use discoloured solutions. Volume: 40–60 μl only. Alternate eye of same rabbit = control (removes individual variation).

4.3Parameters Observed

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#	Parameter	How Tested	Normal Response
1	Pupil Size	Measured with pupillometer; compared to control eye and baseline	Baseline pupil diameter
2	Light Reflex	Shine torch at pupil	Pupil CONSTRICTS. Absent = sphincter pupillae blocked (anticholinergic)
3	Corneal Reflex	Touch cornea at corneoscleral junction with cotton tip brought from the SIDE	Rabbit CLOSES the eye. Absent = cornea anaesthetised (local anaesthetic)
4	Condition of Conjunctiva	Visual inspection	Normally thin and clear. Hyperaemia/redness noted if drug causes irritation.

4.4Observation Table & Expected Results

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Drug	Pupil	Light Reflex	Corneal Reflex	Mechanism
Saline (Control)	Normal	Present	Present	No drug effect
Pilocarpine / Physostigmine	CONSTRICTION	Present	Present	M3 activation → sphincter contracts
Atropine	DILATION	ABSENT ❌	Present	M3 block → sphincter paralysed (passive mydriasis + cycloplegia)
Phenylephrine	DILATION	Present	Present	α1 stimulation → dilator contracts (active mydriasis)
Ephedrine	DILATION	Present	Present	Indirect sympathomimetic → α1 activation
Cocaine	DILATION	Present	ABSENT ❌	NA reuptake block (mydriasis) + local anaesthetic (corneal reflex lost)
Adrenaline	DILATION	Present	Present	α1 direct activation → dilator muscle

⚡ Directly Examinable: Atropine abolishes light reflex; Cocaine abolishes corneal reflex. These are DIFFERENT reflexes — do not mix them up.

5

Individual Drug Discussions

Deep-dive on each drug — mechanism, effects, clinical uses, ADRs, viva answers

Miotic · M3 Agonist Pilocarpine

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Pupil

Miosis

Light Reflex

Present

Corneal Reflex

Present

Feature	Detail
Source	Naturally occurring alkaloid from leaves of Pilocarpus plant
Mechanism on eye	M3 stimulation → (1) Sphincter pupillae → MIOSIS; (2) Ciliary muscle → near vision accommodation; (3) ↑ aqueous outflow through trabecular meshwork → ↓ IOP
Onset of miosis	10 minutes after instillation
Duration	~4 hours
Effect on vision	Near vision IMPROVES. Distant vision is BLURRED.
Effect on IOP	DECREASES IOP — increases aqueous outflow
Clinical uses	1. Chronic open-angle glaucoma. 2. Acute angle-closure glaucoma (emergency). 3. Antidote for atropine/hyoscine poisoning. 4. Xerostomia (dry mouth) after radiotherapy.
ADRs	Burning pain, conjunctival hyperaemia, excessive sweating, salivation, bronchospasm, bradycardia, hypotension, diarrhoea
Special formulation	Pilocarpine Ocusert — slow-release device placed in conjunctival sac for sustained IOP control

Miotic · Anticholinesterase Physostigmine

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Pupil

Miosis

Light Reflex

Present

Corneal Reflex

Present

Class: Reversible anticholinesterase (INDIRECT-acting parasympathomimetic)
Mechanism: Inhibits acetylcholinesterase → ACh accumulates → stimulates M3 → MIOSIS
Key distinction: INDIRECT — works via enzyme inhibition. Pilocarpine is DIRECT — acts on receptor.
Uses: Glaucoma (historical). Systemically reverses anticholinergic poisoning.

Mydriatic · M3 Antagonist Atropine

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Pupil

Mydriasis

Light Reflex

ABSENT ❌

Corneal Reflex

Present

Feature	Detail
Mechanism	Competitive M3 antagonist. Blocks (1) Sphincter pupillae → CANNOT contract → passive MYDRIASIS; (2) Ciliary muscle → CANNOT contract → CYCLOPLEGIA
Duration	7–14 days — very long, not ideal for routine examination
IOP effect	RAISES IOP — mydriasis narrows iridocorneal angle → obstructs aqueous outflow. CONTRAINDICATED in glaucoma.
Clinical uses	Refraction in children (cycloplegia needed). Uveitis/iritis. Pre-anaesthetic. Antidote for organophosphate poisoning.
ADRs	Dry mouth, blurred vision, urinary retention, tachycardia, constipation, raised IOP

Mydriatic · Short M3 Antagonist Tropicamide

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Pupil

Mydriasis

Light Reflex

ABSENT ❌

Corneal Reflex

Present

Onset: 15–30 minutes · Duration: 4–8 hours — much shorter than atropine
Why preferred: Short duration → patient recovers within the day. PREFERRED for examination of lens, vitreous humor, and retina.
Deeply pigmented iris requires more doses (melanin binds the drug)
⚠️ Precaution: Do NOT use soft contact lenses after Tropicamide — preservative absorbed by soft lenses causes eye irritation
⚠️ Volunteers should NOT drive until vision clears
Contraindications: Glaucoma, BPH

Mydriatic · M1 Antagonist Hyoscine (Scopolamine)

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Pupil

Mydriasis

Light Reflex

ABSENT ❌

Corneal Reflex

Present

Unique effects: Pupillary dilation + ↓ salivation (dry mouth) + ↑ heart rate (tachycardia)
Timeline (10 mg oral): Maximum pupillary dilation at ~3 hours. Returns to baseline by 6 hours.
Clinical uses: Motion sickness, uveitis, iritis, pre-anaesthetic, nicotine addiction, sea sickness. Called a 'lie detector drug'.
⚠️ Contraindicated in glaucoma — may precipitate angle-closure crisis

Special · LA + Indirect Sympathomimetic Cocaine

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Pupil

Mydriasis

Light Reflex

Present

Corneal Reflex

ABSENT ❌

Mydriasis: Blocks reuptake of NA → more NA at α1 on dilator pupillae → contraction → MYDRIASIS
Corneal reflex loss: Local anaesthetic → desensitises cornea → corneal reflex ABOLISHED
Light reflex: PRESERVED — sphincter nerve supply intact
UNIQUE: ONLY drug causing both MYDRIASIS (sympathomimetic) AND loss of CORNEAL REFLEX (local anaesthetic)

Special Mention · Opioid Morphine

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Topical application: NOT absorbed locally from the eye — eye drops have NO EFFECT on pupil
Systemic (IV) effect: Stimulates Edinger-Westphal nucleus (parasympathetic oculomotor nucleus) → excessive M3 stimulation → PINPOINT PUPILS (extreme miosis)
Clinical significance: Pinpoint pupils in an unconscious/overdose patient = OPIOID TOXICITY (morphine/heroin/codeine) — key clinical sign

⚡ Classic Trap: Morphine does NOT work topically. Pinpoint pupils only when given IV — via Edinger-Westphal nucleus stimulation. MCQ and viva favourite.

6

CAL in Human Volunteers

Three key volunteer experiments — design, parameters, and expected results

Expt 16Tropicamide 1% — Pupillary Dilation & Accommodation

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Parameter	Detail
Aim	Evaluate effect of Tropicamide 1% on pupillary diameter and accommodation reflex
Subjects	Healthy adults 18–45 years, either sex, written informed consent
Design	Self-control: right eye = test (Tropicamide); left eye = control (untreated)
Exclusion criteria	Glaucoma, BPH, cardiovascular disease, anticholinergic use in past 7 days, soft contact lens wearers
Parameters	1. Pupillary diameter (pupillometer). 2. Accommodation (ability to read fine print)
Recording times	Baseline, 5, 10, 15, 30 min; then 1, 2, 3, 4, 5, 6 hours
Expected results	Pupil dilation maximal at 1 hour. Accommodation lost (cycloplegia — cannot read fine print). Duration: 4–8 hours. Deeply pigmented iris requires more doses.
Statistics	Mean ± SD. Compared by unpaired 't' test

Expt 17Pilocarpine 2% — Miosis & Near Vision

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Parameter	Detail
Design	Self-control: one eye test, other eye control
Parameters	1. Pupillary diameter. 2. Near vision. 3. Distant vision. 4. Heart rate, BP (systemic ADRs). 5. Salivation
Recording times	Baseline, every 5 min up to 55 min; then 1, 1.5, 2, 4, 8 hours
Expected results	Miosis begins at 10 min. Near vision IMPROVES. Distant vision BLURRED. Conjunctival hyperaemia at 5 min. Possible sweating, salivation (systemic cholinergic effects).

Expt 15Hyoscine 10 mg Oral — Pupil, Salivation & Heart Rate

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Parameter	Detail
Design	Randomised single-blind: volunteers receive 10 mg hyoscine or placebo
Salivation measurement	1 g rock salt under tongue for 1 minute → saliva collected in measuring cylinder → volume measured
Recording times	Baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6 hours
Expected results	Pupil dilates. Salivation DECREASES (dry mouth). Heart rate INCREASES. Maximum effect at ~3 hours. Returns to baseline by 6 hours.
ADRs to watch	Dry mouth, blurred vision, flushing, hallucinations, difficulty urinating, photosensitivity

7

The Pupillometer

Used in every miotic/mydriatic experiment — what it is and how to use it

Type	Details
Simple Pupillometer	Stiff paper with parallel holes of increasing size: 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8 mm (half-inch gap between pairs)
How to use it	Volunteer looks at a well-illuminated distant object. Pupillometer held near eye with other eye closed. Volunteer looks through the holes appearing as circles. Size where two circles JUST START OVERLAPPING = pupillary diameter.
Animal use (Rabbit)	Scale-like instrument with holes: 0.5, 1, 1.5, 2, 2.5, 3 mm. Held against the eye and compared to pupil size.
Electronic Pupillometer	Measures pupil size, reaction speed, and light reactivity. Used in neurological assessment, brain injury monitoring, drug/alcohol detection.
Clinical significance	Neurological assessment, drug/alcohol detection, traumatic brain injury monitoring, pharmacological studies

8

Clinical Application — Glaucoma

Most important clinical use of miotics — types, mechanisms, drug groups

8.1What is Glaucoma?

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Glaucoma: progressive optic neuropathy with visual field changes and cupping of the optic disc
Normal IOP: 10–20 mmHg. In glaucoma it can rise to 60 mmHg
Raised IOP compresses optic nerve axons → blocks axonal flow → neurons die → visual field loss → blindness
Glaucoma accounts for 12% of worldwide blindness; 13% of global blindness is in India
Remains UNDETECTED in nearly 50% of cases

Types of Glaucoma

Type	Description & Treatment
Primary Open-Angle Glaucoma (POAG)	Iridocorneal angle is OPEN but increased resistance in trabecular meshwork. Aqueous cannot drain. Most common. Treated with Pilocarpine, Timolol, Dorzolamide, Latanoprost.
Primary Angle-Closure Glaucoma (PACG)	Iris BLOCKS access to outflow channels. Sudden severe IOP rise. Emergency. Treated urgently with Pilocarpine (constricts pupil → pulls iris away from angle → opens drainage). AVOID mydriatics!

⚡ Critical: In angle-closure glaucoma, mydriatics (Atropine, Tropicamide) are CONTRAINDICATED — they dilate the pupil, pushing iris against the drainage angle and WORSENING the IOP crisis.

8.2Drug Groups Used in Glaucoma

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Drug Class	Examples	Mechanism
Cholinergic agonists	Pilocarpine, Carbachol, Physostigmine	↑ aqueous outflow → ↓ IOP
Adrenergic agonists	Epinephrine, Brimonidine	↓ aqueous production
β-Adrenergic blockers	Timolol, Levobunolol, Betaxolol	Block β receptors on ciliary epithelium → ↓ aqueous production
Prostaglandin analogues	Latanoprost, Travoprost, Bimatoprost	↑ uveoscleral outflow (alternative drainage route)
Carbonic anhydrase inhibitors (topical)	Dorzolamide, Brinzolamide	Inhibit aqueous production
Carbonic anhydrase inhibitors (systemic)	Acetazolamide, Methazolamide	↓ aqueous production
Hyperosmotic agents	Glycerol, Mannitol	Draw fluid from eye osmotically — acute emergencies

9

Master Comparison Table & High-Yield Facts

All drugs at a glance + 12 top exam facts + mnemonics

Drug	Class	Pupil	Light Reflex	Corneal Reflex	Key Clinical Point
Pilocarpine	Direct M3 agonist	Constricts	Present	Present	Treats glaucoma (both types). Improves near vision. Onset 10 min.
Physostigmine	Anticholinesterase	Constricts	Present	Present	Indirect miotic. Inhibits AChE.
Atropine	M3 antagonist	Dilates	ABSENT	Present	Cycloplegia + mydriasis. Contraindicated in glaucoma. 7–14 days.
Tropicamide	Short M3 antagonist	Dilates	ABSENT	Present	4–8h. Preferred for fundoscopy/refraction.
Hyoscine	M1 antagonist	Dilates	ABSENT	Present	Also ↓ salivation, ↑ HR. Max at 3 h.
Phenylephrine	Direct α1 agonist	Dilates	Present	Present	ACTIVE mydriasis. No cycloplegia. Safe for fundoscopy.
Ephedrine	Indirect sympathom.	Dilates	Present	Present	Active mydriasis. Releases stored NA.
Cocaine	NA reuptake blocker + LA	Dilates	Present	ABSENT	UNIQUE: Mydriasis + loss of corneal reflex.
Morphine (topical)	Opioid	No effect	No effect	No effect	NOT absorbed topically. IV → PINPOINT pupils via Edinger-Westphal.
Timolol	β-blocker	No change	Normal	Normal	↓ aqueous production → ↓ IOP. Used in glaucoma.

Top 12 High-Yield Facts

1. Sphincter pupillae = M3 (parasympathetic) → Contraction = MIOSIS. Dilator pupillae = α1 (sympathetic) → Contraction = MYDRIASIS.
2. Passive Mydriasis = anticholinergic. Light reflex ABOLISHED. Active Mydriasis = sympathomimetic. Light reflex PRESERVED.
3. Cocaine is UNIQUE — causes both MYDRIASIS (NA reuptake block) AND loss of CORNEAL REFLEX (local anaesthetic).
4. Atropine abolishes LIGHT reflex. Cocaine abolishes CORNEAL reflex. These are DIFFERENT reflexes!
5. Morphine topically = NO effect. Morphine IV = PINPOINT pupils (via Edinger-Westphal nucleus).
6. Tropicamide = preferred for routine fundoscopy. Duration: 4–8 hours. Avoid soft contact lenses.
7. Pilocarpine: Onset 10 min, duration 4 hours. Near vision IMPROVES, distant vision BLURRED. Treats BOTH glaucoma types.
8. Cycloplegia = paralysis of ciliary muscle = cannot accommodate = cannot read fine print. Caused by anticholinergics.
9. Atropine RAISES IOP (contraindicated in glaucoma). Pilocarpine LOWERS IOP (used in glaucoma).
10. Hyoscine: Maximum effect at 3 hours. Decreases salivation, increases heart rate, increases pupil size.
11. Deeply pigmented iris requires MORE doses of mydriatics (melanin binds the drug).
12. Experiment done in DIM LIGHT — strong light causes pupil constriction and confounds results.

Mnemonics

Miotics work on M3 — M for Miosis, M for Muscarinic
Cocaine = C for Cornea (corneal reflex lost). Atropine = A for Absent light reflex
SLUDD = Pilocarpine/cholinergic side effects: Salivation · Lacrimation · Urination · Defaecation · Diarrhoea
Glaucoma drugs: "Please Allow Treatment Prostaglandins & Carbonic" = Pilocarpine, Adrenergics, Timolol, Prostaglandins, Carbonic anhydrase inhibitors

Mydriatics & MioticsEffect of Drugs on the Eye

Anatomy of the Eye — Foundations

Definitions — Miotics and Mydriatics

Classification of Miotics & Mydriatics

The CAL Experiment — Effect of Drugs on Rabbit Eye

Individual Drug Discussions

CAL in Human Volunteers

The Pupillometer

Clinical Application — Glaucoma

Master Comparison Table & High-Yield Facts

Mydriatics & Miotics
Effect of Drugs on the Eye