Ocular Therapeutics

Billie Jean T. Cordero, MD, DPBO

 Ocular Pharmacology

• Pharmacodynamics
• the study of the biochemical and physiologic effects of
drugs and their mechanisms of action

• Pharmacokinetics
• the study of the factors that determine the relationship
between drug dosage and the change in concentration
over time in a biological system
 Ocular Pharmacology
• Bioavailability
• amount of drug absorbed (penetration into ocular tissues)
• Depends on concentration, rate of absorption, tissue binding,
transport, metabolism, and excretion
• Methods of improving bioavailability:
• INCREASE CONCENTRATION
• SURFACTANTS
• OSMOTICS
• INCREASE PH
• INCREASE VISCOSITY
• INCREASE CONTACT TIME
Routes of Administration
Routes of Administration
OCULAR DRUG

LOCAL SYSTEMIC

TOPICAL ORAL

PERIOCULAR INTRAVENOUS

INTRACAMERAL INTRAMUSCULAR

INTRAVITREAL
 Routes of Administration

1. Topical
• EYE DROPS
• 1 drop = 50 μL (20–40 drops in most bottles)
• Conjunctival cul-de-sac holds only 10 μL (20% of drop)
• Drop diluted by reflex tearing and normal tear turnover:
• only ~50% of drug that reaches the cul-de-sac is
present 4 minutes later (10% of drop)
 Routes of Administration

1. Topical
• OINTMENT
• Increases the contact time of ocular medications
• Drugs with high lipid solubility would allow it to
diffuse through the ointment and escape into both
the corneal epithelium and the tears
 Routes of Administration
2. Subconjunctival/Sub-Tenon’s
• increases duration and concentration, bypasses conjunctival and
corneal barriers
• avoids systemic toxicity;
• useful if poor compliance

3. Retrobulbar/peribulbar
• used for anesthesia
Routes of Administration
 Routes of Administration
4. Intraocular
• direct ocular effects
• beware toxicity
• used intraoperatively
(intracameral,
intravitreal)
 Routes of Administration
EYEDROP
Suspension, Solution

OINTMENT
Topical LID SCRUB
GEL
L SOLID DELIVERY DEVICES
Soft contact lens, Collagen shields, Filter paper strips, Cotton pledget
O SUBCONJUNCTIVAL INJECTION
C SUBTENON’S INJECTION
Periocular
A RETROBULBAR INJECTION
L PERIBULBAR INJECTION
INTRAOCULAR ANTIMICROBIAL
(Intracameral) ANESTHETICS (during surgery)

ANTIMICROBIAL
INTRAOCULAR
STEROIDS
(Intravitreal)
ANTI-VEGF
 Routes of Administration
5. Systemic
• must cross blood–ocular barrier (blood– aqueous for anterior
segment, blood–retinal for posterior segment)
• penetrance is improved with decreased molecular size,
decreased protein binding, and increased lipid solubility
#25
 #25

1. 1 drop = ____ μL

2. Except for topical, give 1 local route of

administration for ocular medications
 Classes of Drugs for the Eye

Diagnostic Therapeutic
Local Anesthetic Analgesics
Miotic/ Mydriatic Ocular Hypotensive
Anti-Infectives
Anti-Inflammatories

Antiallergy and Ocular Decongestants

Preparations for Ocular Surface Disease

 Case 1:
24/M
CC: Foreign body sensation, OD

• 3 hrs PTC, after welding, the patient experienced foreign

body sensation, OD associated with slight blurring of
vision and eye redness
• Slit lamp exam: (+) foreign body on corneal surface, OD
• Assessment: Corneal foreign body, OD
• Plan: Removal of corneal foreign body
Anesthetics

• Suppress corneal sensitivity

• Onset = 10 to 20s
• Duration = 10 to 20 min
• Mild burning sensation immediately
follows instillation for about 20 to
30s
• Side effects of chronic use is corneal
desquamation
 Local Anesthetics
MOA Side Effects

• Stabilization of cell membrane, preventing • Depends on systemic

depolarization of peripheral nerves absorption – hepatic
toxicity, convulsions,
• First block the parasympathetic fibers (pupil respiratory or
dilation), sympathetic fibers (vasodilation), myocardial
sensory fibers (pain and temperature), and depression
myelinated fibers (akinesia)
• Transient loss of
vision once there is
leak reaching the
optic nerve
 Commonly Used Local Anesthetics

Local Anesthetic Use

Proparacaine 0.5% • Fast acting topical anesthetic (15
seconds-20 minutes)
• Least irritating to the conjunctivae
Lidocaine 0.5%, 1% and 2% • Used as a topical mucosal anesthesia
• Rapid retrobulbar or eyelid block
lasting 1-2 hours
• Can be used intraocular – 0.3mL of 1%
isotonic
Bupivacaine 0.25%-0.75% • Mixed with lidocaine for longer effect
• Slower onset of action but longer
duration
• Topical

• Intracameral

• Retrobulbar

• Eyelid block
#111
 #111

• Which of the following topical anesthesia is fast

acting and is the least irritating to the conjunctiva

• Give 1 use of topical anesthesia

Autonomic system drugs
Adrenergic Cholinergic

a1,a2,b1,b2 Nicotinic (pre)

Muscarinic (post)
 Case 2:
CC: blurring of vision, OU (OD > OS)
• 60 / F, diagnosed with
uncontrolled diabetes
mellitus x12 years

• Need for retina exam -

(Indirect
Ophthalmoscopy)
 PUPILLARY DILATION / CONSTRICTION

MYDRIATICS MYDRILYTICS CYCLOPLEGICS

Act on adrenergic receptors of the

Action autonomic nervous system
Cholinergic receptors

Adrenergic receptor
Adrenergic agonist or Anticholinergics, Aantimuscarinics,
Class Sympathomimetics
antagonist or
Cholinergic blocking agents
Anti-adrenergics

Function Dilates the pupil Constricts the pupil Dilates the pupil

1. Atropine sulfate
• Phenylephrine
2. Homatropine-hydrobromide
• Hydroxy-
Examples amphetamine
1. Dapiprazole 3. Scopolamine hydrobromide
4. Cyclopentolate hydrochloride
• Cocaine
5. Tropicamide
 Cholinergic drugs
• Direct-acting agonists
• act on end organ --- therefore, do not need intact innervation
• shallowing of anterior chamber (AC)
• disruption of blood–aqueous barrier
• miosis
• decrease in IOP
• Acetylcholine
• Miochol - very short-acting, unstable, used intracamerally,
• Carbacholine (carbamylcholine, carbachol; direct and indirect
acting)
• Pilocarpine - less potent than ACh, but resistant to AChE;
no miosis if IOP >40 mmHg)
 Case 3:

• Penalization of the eye, paralysis of accommodation

 CYCLOPLEGICS

ATROPINE CYCLOPENTOLATE TROPICAMIDE

Non-selective Non-selective Non-selective
Class
Antimuscarinic Antimuscarinic Antimuscarinic
Onset 12 s 20 to 30 min 20 to 30 min
7 to 12 days 24 h 6h
Duration
(long-acting) (intermediate-acting) (short-acting)
1. Pupillary
dilation 1. Pupillary dilation 1. Pupillary dilation
Function 2. Paralysis of 2. Paralysis of 2. Paralysis of
accommod accommodation accommodation
ation

30
 Case 5:
35 / F
CC: sudden blurring of vision OD

• While watching a movie, there was sudden pain, blurring of

vision, and eye redness, OD

• Intraocular Pressure of 50mmHg

 GLAUCOMA
• Glaucoma - disease of the optic nerve
• characterized by a particular pattern of progressive damage
to the optic nerve that generally begins with a subtle loss of
side vision (peripheral vision)
TYPES OF GLAUCOMA
TREATMENT OF GLAUCOMA
• Glaucomatous optic nerve damage is irreversible
• Goal of treatment:
• Decrease intraocular pressure (IOP)
• Control or retard the progression of optic nerve damage that leads
to visual loss
 OCULAR HYPOTENSIVES
β-ADRENERGIC
PROSTAGLANDIN ADRENERGIC
ANTAGONISTS
ANALOGUES AGONISTS
(β-BLOCKERS)

Dose Once a day 2x a day 3x a day

Decrease aqueous humor

Increase uveoscleral Decreasing aqueous
Function outflow humor production
production and increase
uveoscleral outflow

1. Timolol
1. Latanoprost 2. Betaxolol
1. Apraclonidine
Ex. 2. Travoprost 3. Levobunolol
2. Brimonidine
3. Bimatoprost 4. Metipranolol
5. Carteolol
 OCULAR HYPOTENSIVES
CARBONIC ANHYDRASE
CHOLINERGIC AGONISTS
INHIBITORS (CAI)

250mg PO q6h
Dose Topical: 3x a day
2x a day

Function Decreasing aqueous humor production Increase uveoscleral outflow

1. Acetazolamide (250 mg tablet)

1. Pilocarpine
2. Methazolamide eyedrops
Examples 3. Dorzolamide eyedrops
2. Carbachol
3. Echothiophate
4. Brinzolamide eyedrops
OCULAR HYPOTENSIVES
#1
 #1

• Two types of Glaucoma

• Give 1 function of your anti glaucoma medications

 Case 6:

• 11 / M, CC:
Periorbital swelling,
Left

• 60 / M, CC: Blurring
of vision, OS
 ANTI-INFECTIVES: ANTI-BACTERIAL

INHIBITING
DISRUPTING BINDING OF DRUG
CELL WALL
BACTERIAL CELL TO BACTERIAL
SYNTHESIS OF
MEMBRANES RIBOSOMES
PEPTIDOGLYCANS

Attacks structural Attacks structural inhibiting bacterial

Function
integrity of bacteria integrity of bacteria protein synthesis

1. Aminoglycosides
Neomycin,
Gentamicin,
1. Penicillin Tobramycin,
2. Cephalosporin 1. Polymixin B Amikacin
Examples
3. Bacitracin 2. Gramicidin 2. Tetracyclines
4. Vancomycin Doxycycline
3. Macrolides
4. Chloramphenicol
 ANTI-INFECTIVES: ANTI-BACTERIAL

INHIBITION OF ENZYMES
INHIBITING FOLIC ACID
DNA GYRASE AND
SYNTHESIS
TOPOISOMERASE IV

Attacks structural integrity of Attacks structural integrity of

Function
bacteria bacteria
1. Fluorinated Quinolones
(Fluoroquinolones)
Lomefloxacin,
1.Sulfonamides Norfloxacin,
Examples 2.Pyrimethamine Ciprofloxacin, Ofloxacin,
3.Trimethoprim Sparfloxacin,
Gemifloxacin,
Levofloxacin,
Moxifloxacin
 ANTI-INFECTIVES: ANTI-VIRAL

ADENOVIRUS
HERPES SIMPLEX CYTOMEGALOVIRUS
(SEROTYPES 3, 7,
VIRUS (HSV-1) (CMV)
8, 19, AND 37)

interfere with viral replication and multiplication

Function by inhibiting thymidinekinase needed for nucleic acid synthesis

1. Penicillin
2. Trifluridine
NO antivirals are NO antivirals areapproved for
3. Acyclovir
Examples 4. Valacyclovir
approved for ocular ocular cytomegalovirus
adenoviral infections infections
5. Famcyclovir
6. Gancyclovir
 ANTI-INFECTIVES: ANTI-FUNGAL

POLYENES PYRIMIDINES

increase cell permeability by

Inhibit DNA synthesis by
Function binding ergosterol in the cell
blocking thymidinekinase
membrane

1. Flucytosine
Examples 1.Amphotericin B
2.Natamycin
 ANTI-INFECTIVES: ANTI-FUNGAL

AZOLES ECHINOCANDINS

increase cell permeability by

weaken the cell wall by
Function binding ergosterol in the cell
inhibiting glucan synthesis
membrane

1.Amphotericin B
1. Caspofungin
2.Ketoconazole
2. Micafungin
3.Miconazole
Examples 4.Itraconazole
3. Anidulafungin
5.Fluconazole
6.Voriconazole
 Case 7:
25 / F
CC: Blurring of vision

• 1 wk PTC, sudden BOV, OD assoc with eye pain, haloes

around light, and photophobia

• Slit lamp exam: Inflammatory cells in anterior chamber

• Diagnosis: Acute Anterior Uveitis, OD

 ANTI-INFLAMMATORY
AGENTS
- Ocular inflammation can be treated with drugs
administered topically, by local injection or
ocular implantation, or systemically.

- Classifications:
1. Glucocorticoids
2. NSAIDS
3. Antihistamines
4. Histamine release blockers
5. Antifibrotics
 ANTI-INFLAMMATORIES
CORTICOSTEROIDS NSAIDs CYCLOSPORIN
a calcineurin inhibitor, a
Inhibits phospholipase of Inhibits cyclooxygenase
cytochrome P450 3A4
Action inflammatory prostaglandin of inflammatory
inhibitor, and a P-
pathway prostaglandin pathway glycoprotein inhibitor

Function Suppress inflammation Decrease pain immunosuppressant

SHORT ACTING
1.Hydrocortisone
2.Cortisone
3.Prednisone
INTERMEDIATE ACTING 1. Ketorolac
Examples 1.Trimcinolone 2. Diclofenac
1. Cyclosporin A
2.Fluprednisolone
LONG ACTING
1.Dexamethasone
2.Betamethasone
EXAMPLES OF ANTI-INFLAMMATORIES

TOPICAL LOCAL INJECTION SYSTEMIC

Prednisolone acetate
Dexamethasone Anecortave Acetate Prednisone
Fluoromethalone Triamcinolone Methylprednisolone
Rimexalone Methylprednisolone Dexamethasone
Loteprednolone
ANTI-INFLAMMATORY AGENTS

Adverse Effects of Glucocorticoids

▪ Complications in the EYE:
- Glaucoma
- Posterior subcapsular cataracts
- Exacerbation of bacterial and viral (herpetic)
infections through suppression of protective immune
mechanisms
- Ptosis
- Mydriasis
- Scleral melting
- Eyelid skin atrophy
ANTI-INFLAMMATORY AGENTS

Adverse Effects of Glucocorticoids

- Steroid-induced IOP increase may occur
(topical, periocular, nasal, & systemic)
Glaucoma - Approx. 4% develop pressure higher than 31
mmHg after 6 weeks with topical
dexamethasone
→ Almost never occurs in less than 5
days and rarely in less than 2 weeks

** IOP monitoring is required at periodic intervals during

the entire course of chronic steroid therapy to prevent
iatrogenic glaucomatous nerve damage.
ANTI-INFLAMMATORY AGENTS

Adverse Effects of Glucocorticoids

▪ Oral doses can cause:
- Suppression of the pituitary-adrenal axis
- Gluconeogenesis resulting from hyperglycemia, muscle wasting,
osteoporosis
- Redistribution of fat from the periphery to the trunk
- Central nervous system effects such as euphoria
- Insomia
- Aseptic necrosis of the hip
- Peptic ulcer
- Diabetes
- Occasionally, psychosis
 Case 8:

• 10 / M, CC: Bilateral eye itchiness

• HPI: On & off eye itchiness assoc with eye

redness and swelling

• Eye exam: Papillae on the palpebral

conjunctiva of the upper lids and Trantas dots
on both eyes

• Diagnosis: Vernal keratoconjuntivitis

 ANTI-ALLERGY
• Used for allergic conditions

• Anti-histamintes
• Naphazoline
• Levocabastine

• Mast-cell stabilizers
• Olapatadine
• Cromolyn
 ANTIALLERGY & OCULAR
DECONGESTANTS
DECONGESTANTS ANTIHISTAMINES MAST CELL STABILIZER

Synthetic adrenergic Inhibits inflammatory Inhibit type I immune

Action agonists prostaglandin pathway response

Conjunctival Preventing mast cell

Function vasoconstriction
Inhibit the action of histamine
degranulation

ORAL SEDATING
1.Diphenhydramine
2.Promethazine
ORAL NONSEDATING
1.Fexofenadine
1. Phenylephrine 2.Loratadine 1. Ascromolyn sodium
2. Naphazoline 3.Desloratadine 2. Lodoxamide
Examples 3. Oxymetazoline, 4.Cetirizine 3. Nedocromil
TOPICAL FIRST GENERATION
4. Tetrahydrozoline 4. Pemirolast
1.Pheniraminemaleate
2.Antazoline
TOPICAL SECOND GENERATION
1.Ketotifen
2.Olopatadine
 Case 9:
23 / F
CC: Tearing, OU

• associated with eye pain and foreign body sensation

• Symptoms worsen especially during exam week

#69
 #69

• Give one complication of prolonged use of topical

steroid

• Give one contraindication for topical steroids

 TEAR FILM
DYSFUNCTION
TEAR FILM

• Mucin layer

• Aqueous layer

• Lipid layer
 OCULAR LUBRICANTS

• Used for Dry eye

• Varied formulations

• Examples:
• Polyethylene glycol (PEG)
• Hypromellose
• Methylcellulose

• Often have preservatives (benzalkonium chloride)

• Preservative-free medications for more frequent dosing (q1h)

 DRUGS FOR OCULAR SURFACE
DISEASE

ARTIFICIAL TEARS OINTMENTS

(NON-MEDICATED)

Reproduce metabolic, optical,

Create a lipid layer that retard
Function and physical characteristics of
evaporation
natural tears

Moderate to severe dry eye,

Lagophthalmos, Exposure
Indication Treatment of Dry Eye
keratopathy, or severe corneal
epithelial compromise

1. Methylcellulose (MC) 1. Petrolatum

2. Polyvinyl alcohol (PVA) 2. Mineral oil
Examples 3. Povidone 3. Lanolin
4. Dextran 4. Lanolin alcohols
5. Propylene glycol
 ANTIBIOTICS
Principal Antibiotic Agents
Drug Name Topical Intravitreal Intravenous
Cefazolin sodium 50 mg/mL 2250 g 2-4g (3-4 doses)
Ceftazidime - 2200 g 1g (2-3 doses)
Erythromycin 50 mg/mL 500 g -
Gentamicin sulfate 8-15 mg/mL 100-200 g 3-5 mg/kg (2-3 doses)
Neomycin sulfate 5-8 mg/mL - -
Penicillin G 100,000 units/mL - 12-24M units (4 doses)
Polymyxin B sulfate 10,000 units/mL - -
Tobramycin sulfate 8-15 mg/mL 100-200 g 3-5 mg/kg (2-3 doses)
Vancomycin HCl 20-50 mg/mL 1000 g 15-30 mg/kg (1-2 doses)
 ANTIBIOTICS
Ophthalmic Antibacterial Agents
Generic Name Trade Name Solution Strength (%)

Erythromycin generic 0.5% ointment

Gatifloxacin Zymar 0.3% eye drops

Gentamycin Garamycin 0.3% eye drops

generic (ointment) 0.3% ointment

Levofloxacin Quixin 0.5% eye drops

Moxifloxacin HCl Vigamox 0.5% eye drops

Ofloxacin Ocuflox 0.3% eye drops

Tobramycin sulfate Tobrex 0.3%

** There are available mixture agents and combinations (anti-inflam + antibi)

 ANTIFUNGALS
Antifungal Agents
Drug Name Route Dosage Indication
Amphotericin B Topical 0.1-0.5% solution Aspergillus
(Fungizone) Candida
Crystococcus (Blastomyces)
Subconjunctival 0.8-1.0 mg (Coccidioides)
Intravitreal 5 g (Colletotrichum)

Natamycin Topical 5% suspension Fusarium (Aspergillus)

(Natacyn) (Candida)
(Cephalosporium)
(Curvalarie)
(Penicillum)
Ketoconazole Oral 200mg daily to 400mg Blastomyces
(Nizoral) for severe or Candida
incomplete response Coccidioides
Histoplasma
 ANTIFUNGALS
Antifungal Agents
Drug Name Route Dosage Indication
Fluconazole Oral 200 mg daily Candida
(Diflucan) Crystococcus
(Acremonium)

Itraconazole Oral 200 mg daily Aspergillus

(Sporanox) Blastomyces
IV Histoplasma
(Candida)
(Curvularia)
(Fusarium – nonsevere)
Flucytosine Oral 50-150 mg/kg daily Candida
(Ancobon) every 6 hrs Crytococus
Topical 1% solution (Aspergillus)
 ANTIVIRALS
Antiviral Agents
Drug Name Systemic Dosage

Acyclovir sodium • Oral: Herpes simplex keratitis (HSV) 200mg 5x daily for 7-10 days.
(Zovirax) • Oral: Herpes zoster ophthalmicus (HZV) 600-800mg 5x daily for 10
days.
• IV if patient is immunocompromised.

Famciclovir • 500mg 3x daily for 7 days.

(Famvir HZV) (*with possible dosage adjustments d/t potential toxic & S/E)

Valacyclovir • 1g 3x daily for 7 days.

(Valtrex) (*asso. w/ Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome)

Ganciclovir • Intravitreal: 4.5mg sterile intravitreal insert designed to release

(Vistresert) the drug over a 5-8 mo period

Ganciclovir sodium • IV induction: 5mg/kg every 12 hrs for 14-21 days

(Cytovene) • Maintenance: 5mg/kg daily for 7 days
Ocular Toxicity
 RESOURCES

• Trattler,W., Kaiser,P., Friedman, N., Review of

Ophthalmology 2nd edition

• American Academy of Ophthalmology, Basic and

Clinical Science Course Vol. 2: Fundamentals and
Principles of Ophthalmology

• Ocular Pharmacology slides by Dr. Jesse Baula

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