Download Mydriatic / Cycloplegic

NBEO Ocular Pharmacology &
Therapeutics Review
John A. McGreal, O.D.
2005
JAM
John A. McGreal Jr., O.D.
Missouri Eye Associates
 McGreal Educational Institute
 11710 Old Ballas Rd
 Suite 102
 St. Louis, MO 63141
 Phone: 314.569.2020
 Fax: 314.569.1596
 email: [email protected]
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JAM
Mechanism of Action - LA
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Increase in threshold for electrical excitation
Decreased conduction velocity without depolarization
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Decreased permeability of cell membrane to Na+ ions
Order of disappearance and recovery of senses
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Reversibly blocks nerve conduction
Recovery with no residual damage
Pain / temperature (cold/warmth) / touch / proprioception / skeletal
muscle tone
Progression of affect related to diameter, myelination and
velocity of nerve fiber
Loss of sensation without loss of consciousness
JAM
Types of LA
Topical or surface anesthesia – applied to skin or
mucous membranes
 Injectable anesthesia
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Infiltration – injection into tissue area along incision / trauma
Field block anesthesia – infiltrate tissue around (not on)
Nerve block anesthesia – injected close to a nerve to block a
greater area
Regional anesthesia – Spinal, Epidural, IV regional
JAM
Classification of LA
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LAs are all synthetic with the exception of cocaine
Esters - derivatives of para-amino-benzoic acid (PABA)
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Metabolized by hydrolysis of the ester linkage by plasma esterase
All commonly used topical anesthetics are of the ester type
Allergic reactions to LA occur almost exclusively to ester linkages
Esters of benzoic acid: Cocaine
Esters of meta-aminobenzoic acid: Proparacaine (Ophthetic, Ophthaine,
Alcaine)
Esters of para-aminobenzoic acid:
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Procaine (Novocaine)
Tetracaine (Tetracaine, Pontocaine)
Benzoxinate/fluorescein (Fluress, Fluorocaine, Flurate, Flu-Oxinate)
JAM
Classification of LA

Amides - derivatives of aniline
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Metabolized by liver, excreted in urine
Amides of benzoic acid
 Lidocaine (Xylocaine)
 Mepivascaine (Carbocaine)
 Bupivacaine (Marcaine)
 Etidocaine (Duranest)
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Cocaine
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Benzoic acid ester
2%
Onset = 5-10min
Duration = 20 min (total) & 1-2 hrs (partial)
More effective and prolonged conjunctival anesthesia
More prolonged corneal anesthesia, but not as effective
Facilitates epithelial debridement by loosening cells
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
HSV, band keratopathy, RCE
Diagnostic drug of choice in Horner’s syndrome
Schedule II drug
Benzoxinate
PABA ester
 0.4%
 Onset = 20sec
 Duration = 10min
 May have cross sensitivity to Tetracaine
 Least diminution of fluorescence
 Available only in combination with 0.25% sodium
fluorescein as Fluress, Flu-Ox

Tetracaine
PABA ester
 0.5%
 Onset = 20sec
 Duration = 10min
 Alternative to proparacaine if sensitivity has occurred
 More frequent allergic reactions and corneal
compromise than with proparacaine
 Available as Tetracaine

Proparacaine
MABA ester
 0.5%
 Onset = 15 sec
 Duration = 15min
 No cross sensitivity with tetracaine or benzoxinate
 Topical anesthetic of choice
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Least irritating
May decrease fluorescence
Available as Alcaine, Ophthaine, Ophthetic
Tropicamide
Mydriatic / Cycloplegic
 Parasympatholytic drug of choice for dilation
 0.5%, 1%
 Weakest cycloplegics
 Mydriasis in 20-30min
 Duration of mydriasis – 6 hours
 Available as Tropicamide
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Phenylephrine
Mydriatic
 Sympathomimetic drug of choice for dilation
 2.5%, 10%
 No cycloplegic action
 Mydriasis in 20-30min
 Pupil will still constrict with bright light
 Minimum side effects with 2.5%
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Increases heart rate and BP
Available as Neo-synephrine
JAM
Hydroxyamphetamine HBr
Mydriatic
 Hydroxyamphetamine 1% and Tropicamide 0.25%
 Rapid onset of mydriasis
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May be incomplete mydriasis
One drop convenience
Only partial loss of accommodation
 Due
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to lower concentration of Tropicamide
Recovery begins within 90 minutes
Available as Paradrine (0.125% Tropicamide)
 Available as Paremyd (0.25% Tropicamide)
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Atropine sulfate
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Prototype - no residual accommodation
1%
Cycloplegic of choice in children under age 4 with
accommodative esotropia
Maximum cycloplegia within 6 hours
Duration 10-18 days of cycloplegia, 14-21 days of dilation
Often dispensed to parent to instill (ung) tid for three days prior
to refraction and motility examinations
For a 4.5kg child, lethal dose is about 10mg (20 drops of 1%
solution)
Available as Atropine
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Scopolamine
Mydriatic / cycloplegic
 0.25%
 Similar to atropine but with quicker onset and shorter
duration
 Cycloplegic retinoscopy in patients sensitive to atropine
 Maximum cycloplegia within hours
 Duration days of cycloplegia, days of dilation
 Available as Scopolamine, Hyoscine, Isoptohyoscine
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Cyclopentolate
Mydriatic / Cycloplegic
 0.5%, 1%, 2%
 Cycloplegic of choice for most children and all adults
 Use 1% solution; two drops separated by 5 minutes
 Cycloplegia maximum at 30-60min
 Duration – 8-24 hours
 Minimal residual accomodation (<1D)
 Available as Cyclogyl
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Tropicamide
Mydriatic / Cycloplegic
 0.5%, 1%
 Drug of choice for routine dilation
 Cycloplegia maximum at 20-30min
 Duration of cycloplegia – 5-10min
 Minimal residual accommodation (3.5D)
 Cannot guarantee adequate cycloplegia
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Incomplete and short acting
Available as Mydriacyl
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Homatropine
Mydriatic / cycloplegic
 2%, 5%
 Drug used primarily for treatment of uveitis
 Useful in patients sensitive to cyclopentolate
 Cycloplegia maximum at 40-60min
 Duration of mydriasis – 1-3 days
 Moderate residual accommodation, incomplete
cycloplegia
 Available as Homatropine
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Horner’s Syndrome
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Diagnostic signs
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Ipsilateral ptosis
Ipsilateral miosis
Facial anhydrosis
Conjunctival hyperemia (transient)
Ocular hypotony
Heterochromia iridis (if congenital)
Etiology – ipsilateral interruption of the sympathetic
outflow to the head and neck
Horner’s Syndrome
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Central neuron is in the brainstem and cervical chord (from the
hypothalamus to the ciliospinal center of Budge at C8 to T2)
Preganglionic neuron is in the chest and neck (from cervical
chord via stellate ganglion at the pulmonary apex to the superior
cervical ganglion at the carotid bifurcation
Postganglionic neuron penetrates the base of the skull and
passes through he cavernous sinus to enter the orbit (from the
superior cervical ganglion at the angle of the jaw via the carotid
plexus, the cavernous sinus and the long ciliary nerves to the
iris)
Horner’s Syndrome
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Cocaine test (4%)
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Dilates the pupil only when the sympathetic pathway is intact
and NE is being released from the nerve endings in the dilator
muscle
Dilation of the pupil with cocaine is reduced or absent in any
patient with a defect in this pathway, regardless of which
nerve is involved
Horner’s Syndrome
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Hydroxyamphetamine 1% (Paradrine) test
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Indirect acting adrenergic agonist that acts by releasing NE
from the nerve endings in the dilator muscle
Mydriatic effect only when the postganglionic sympathetic
pathway to the eye is intact and there is endogenous NE
Distinguishes between central or preganglionic lesions and
postganglionic
Adies’ Syndrome
Damage to the ciliary ganglion or short ciliary nerves
 Clinical signs
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Unilateral accommodative paresis
Unilateral mydriasis with poor pupillary reaction to direct
light
 Regional
/ sectoral palsy of the iris sphincter
 Iris stromal streaming or spreading
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Cholinergic supersensitivity of the denervated muscles
Strong pupillary response to near
Adies’ Syndrome
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Etiology
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Postganglionic, parasympathetic denervation
Local infection (pox), inflammation (ciliary ganglionitis) or
injury / orbital surgery
Widespread peripheral neuropathy (DM)
Adie’s syndrome is a form of tonic pupil in which no local
cause for the denervation is evident and there is no peripheral
neuropathy to account for the tendon areflexia
 Benign
Adies’ Syndrome
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Pilocarpine Supersensitivity Test (0.12%)
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A weak concentration of pilocarpine does not usually
constrict the normal pupil but does constrict the tonic pupil
 Cholinergic
hypersensitivity of the denervated iris sphincter
Third Nerve Palsy
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Etiologies
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Supratentorial space occupying lesions, basal aneurisms,
meningitis, ischemic oculomotor palsy, parasellar tumor or
inflammation, diabetes (pupil sparing)
Diagnosis
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Clinical signs and symptoms
Eye down and out
Ptosis
Pilocarpine (0.12%) checking for cholinergic hypersensitivity
 If
no response, then Pilocarpine 1-2% and pupil should constrict
Anticholinergic Mydriasis
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Etiologies
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Accidental exposure of the eye to drugs or substances with
anticholinergic properties
Pharmacologic evaluation
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Pilocarpine 0.5% or 1.0% instilled into each eye
 Pilocarpine
will fail to activate the receptors and constrict the pupil
if muscarinic receptor sites on the effected iris sphincter are
occupied by an anticholinergic drug (pharmacologic blockade)
 Pilocarpine 1.0% will constrict a pupil that is dilated due to
compression
Mydriatic / Cycloplegic
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Hydroxyamphetamine hydrobromide 1.0% /
Tropicamide 0.25% (Paremyd / Acorn)
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Unique combination
One drop convenience
Onset of action occurs within 15 minutes
Only partial loss of accomodation due to lower concentration
of tropicamide
Recovery begins within 90 minutes
JAM
Dermatologic Therapy - Topical
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Low Potency Corticosteroids
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Higher Potency Corticosteroids
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Betamethasone Valerate 0.1% (Valisone)
Triamcinolone 0.1%, 0.05% (Aristocort-A)
Non-steroidal anti-inflammatory
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Hydrocortisone Cream 1.0% (Hytone)
Triamcinolone 0.025% (Aristocort-A)
Pimecrolimus 1% cream (Elidel)
Tacrolimus 1% (Protopic)
Antifungal
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Metronidazole 0.75% (MetroCream, Gel/Galderma)
Azelaic acid 15% gel (Finacea/Berlex) bid
JAM
Ocular Allergies - Oral Therapy
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Antihistamines
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Diphenhydranine (Benadryl 50mg qid)
Loratadine (Claritin 10mg qd/ClaritinD24Hour/ClaritinSyrup 10mg per 10ml/ClaritinRediTabs)
Desloratidine (Clarinex 10 mg qd)
Citirizine (Zyrtec 10mg qd)
Fexofenadine (Allegra 180mg qd)
Corticosteroids
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Deltasone ( Prednisone 1mg/kg/D)
Medrol 4mg DOSPAK (Methylprednisolone)
 Convenient,
pre-packaged six day, 21 tablet tapered course
JAM
Ocular Allergies - Oral Therapy
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Loratadine (Claritin) - OTC
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Claritin 10mg qd
Claritin-D 24Hour 10mg qd - Extended Release Tablets
Claritin Syrup 10mg per 10ml qd - for children 6 and older
Claritin RediTabs 10mg qd - for adults and children 6 and
older
 If
convenience is important
 Mint flavored
 Dissolves on tongue without water
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Loratidine (Alavert) 10mg – OTC
JAM
Ocular Allergies = Satisfied Patients
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51 million Americans suffer from allergies
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OTC use is prevalent and problematic
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Ocular allergies second only to nasal symptoms
Adverse impact on contact lens patients
41% of allergy sufferers believe OTC work well enough
41 million bottles of OTC eye drops are purchased yearly
5 million prescriptions of allergy eye drops written
Who is doing the majority of the treatment?
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41% OD/MD (eye)
59% Non-eyecare specialists
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Ocular Allergies - Topical Therapy
Artificial Tears
 Antihistamine
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Levocabastine (Livostin)
Olopatadine (Patanol), Patanol QD or XL coming soon
Emadastine (Emadine)
Ketotifen (Zaditor)
Astelastine (Optivar)
Epinastine (Elestat)
JAM
Ocular Allergies - Topical Therapy
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Mast Cell Inhibitors
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Cromolyn (Crolom, Opticrom)
– Lodoxamide (Alomide)
– Nedocromil (Alocril)
– Pemirolast (Alamast)
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
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Flurbiprofen (Ocufen)
Profenal (Suprofen)
Diclofenac (Voltaren)
Ketorolac (Acular)
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Ocular Allergies - Topical Therapy
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Corticosteroids
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Medrysone (HMS)
Fluorometholone (FML, Flarex, Eflone)
Prednisolone (Pred forte, Inflamase forte, Econopred)
Dexamethasone (Decadron)
Rimexolone (Vexol)
Loteprednol 0.5% (Lotemax)
 Combination
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with tobramycin 0.3% (Zylet)
Loteprednol 0.2% (Alrex)
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Intraocular Steroid Delivery
System
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Cataract Surgery
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Dexamethasone Drug Delivery System (DEX DDS)
 intraocular
 biodegradable
polymer
 60ug dexamethasone
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Advantages
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compliance
staff time
pharmacokinetics
JAM
Classification of Dry Eye
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Tear Deficient Dry Eye
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Sjogren Syndrome Dry Eye
 Primary-Sjogren,
Congenital Alacrima
 Secondary-RA, SLE, Scleroderma, Wegener’s Granulomatosis,
Polyarteritis, Primary Bilary Cirrhosis, MCTD
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Non-Sjogren Dry Eye
 Lacrimal
Disease-Sarcoid, HIV, GVHD, Congenital, Dacryoadenitis
 Lacrimal Destruction-Pemphigoid, Burns, Erythema Multiforme,
Trachoma, Trauma
 Reflex-Neurotrophic Keratitis, Contact lens, Bell’s Palsy
JAM
Classification of Dry Eye
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Evaporative
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Oil Gland
 Anterior
Blepharitis
 Posterior Blepharitis-Obstructive, Meibomian Gland Disease
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Lid Related
 Blink
Disorders
 Disorders of Lid Aperture
 Disorders of Lid /Globe Congruity
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Contact Lens
Ocular Surface Disorder-Xerophthalmia
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Treatment Modalities
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Artificial Tears/Ointments
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Tears Naturale P.M. preservative free & TearsNatural Forte
(Alcon),Tears Again (Cynacon) & Genteal Gel (Ciba), TheraTears
Liquid Gel (Advanced Vision Research), Refresh Endura
(Allergan), Systane (Alcon)
Punctal Occlusions - Shuttle (Odyssey)
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Tears Naturale PORT (Alcon/Landec Corp)
Smart Plug (Medennium)
Cholinergics - Oral Pilocarpine HCL/Salagen 5mg qid
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Cyclosporin (Restasis/Allergan)
 Tacrolimus (FK-506/Sucampo Pharmaceuticals –
phase II for KCS
 Diquafosol (Inspire-phase III for KCS)
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Treatment Modalities
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Dietary Supplements
– TheraLife Eye & TheraLife Enhancer (TheraLife)
 Beta
carotene, bilberry, chrysanthemum, copper, fructus lycii,
Vitamin E & C, riboflavin (B2), selenium, semen cassiae, zinc
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Hydrate Essential (Cynacon/Ocusoft)
 Essential
fatty acids - Flaxseed oil and bilberry extract
encapsulated in hydroxylated lecithin
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HydroEye (Science Based Health)
 Blend
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of omega fatty acids and nutrients
TheraTears Nutrition (Advanced Vision Research)
 EPA enriched
flaxseed oil
JAM
Treatment Modalities
Pulse Steroids
 Androgen hormone therapy
 Autologous serum
 Limbal stem cell transplantation
 Amniotic membrane transplant
 Humidifier
 Doxycycline
 Warm compresses
 Tarsorrhaphy
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JAM
Nerve Growth Factor - NGF
Important advance in persistent epithelial defects (PED)
 Polypeptide - 1950
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Essential for survival/growth of neurons in CNS
Induces neurite sprouting by neuronal cells
 increases
corneal sensitivity
 promotes epithelial healing
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No ocular / systemic side effects
Dosage
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200ug in 1ml BSS q2h X 2 D, then q4h until healed
Autologous Serum for PED
Tears contain EGF, vitamin A, TGF-B, fibronectin and
other cytokines…..all found in serum
 40ml of blood from venipuncture centrifuged for 5 min
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diluted to 20% by physiologic saline (empiric)/UV bottle
Dosed at 6-10 X/D with additional AFTs
Results
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43% healed within 2 wks, all within several months
Serum accelerates migration of corneal epithelial cells
Serum upregulates mucin expression of corneal epithelium
Amniotic Membrane
Transplantation (AMT)
Ocular surface reconstruction in SJS, severe dry eye,
and severe chemical burns
 Human amniotic membrane prepared from placenta of
elective cesarean section in seronegative (HIV, HepB
&C, syphilis)
 Facilitates epithelialization, reduces inflammation,
vascularization and scarring
 Limbal stem cell transplantation is needed in concert
with AMT in the most severe chemical burns

Cyclosporin-A 0.05% (Restasis)
T-cell lymphocyte suppressor
 Organ transplant rejection
 Substitute for steroids in patients with complications
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20-30% steroid responders
92% glaucoma patients
12-50% PK patients have increased IOPs
Disadvantages
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Availability
Cost
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Cyclosporin-A 0.05%
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Advantages
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Inhibits T-cell lymphocytes
No increase in IOP
No decrease in wound healing
No cataractogenesis
No effect on viral replication
Clinical Applications
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Post-Keratoplasty-Glaucoma/herpes
Keratitis-Thygeson’s/fungal/atopic/VKC
Chronic Uveitis/JRA
Dry Eye Syndromes / Post LASIK dryness
JAM
Cyclosporin-A 0.05% (Restasis)
Allergan
 FDA approved for keratoconjunctivitis sicca

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Increased Shirmer’s test at six months
Dosage – BID
 Supplied as 0.4ml vials, 32 vials per box
 Contraindications – active ocular infections
 Side effects – burning (17%), hyperemia, discharge,
epiphora, FBS all 1-5%
 Pearls - Not just for severe dry eye syndrome, it works
sooner than you have heard and it works well
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Antimicrobial - Topical Therapy
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Antibiotics
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Sulfacetamide (Bleph)
Erythromycin (Ilotycin)
Bacitracin (Bacitracin)
Bacitracin/Polymixin B (Polysporin)
Gentamycin (Garamycin)
Tobramycin (Tobrex)
Antibiotic/Steroid Combinations
JAM
Antimicrobial - Topical Therapy
Trimethoprin/Polymixin B (Polytrim)
 Fluoroquinolones
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Ciprofloxacin (Ciloxan) * generics from B&L, NovexPharma
Ofloxacin (Ocuflox)
Norfloxacin (Chibroxin)
Levofloxacin (Quixin)
Fluoroquinolone combinations
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Ciprofloxacin/Dexamethasone
Ofloxacin/ Prednisolone acetate
 New
4th generation fluoroquinolones
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Bacterial Keratitis Treatment Protocol
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Culture directed/Fortified antibiotics
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Empiric - no culture
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Tobramycin 15mg/ml & Cephazolin 50mg/ml
Moxifloxacin (Vigamox) monotherapy
Gatifloxacin (Zymar) monotherapy
Levofloxacin 1.5% (IQUIX) monotherapy
Non-severe, small, peripheral
Combination - culture
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4th generation & Cephazolin
Severe, large, central
Alternative choices include vancomycin, neosporin
Adjunctive Tetracycline
Inhibits collagenase (in vivo/vitro)
 Inhibits PMNs
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reduces ascorbate levels
decreases phagocytosis & chemotaxis
Current recommendation
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TCN 250mg PO qid
Doxycycline 100mg bid
Resistance To Fluoroquinolones
In vitro data differs from in vivo
 Streptococcus: “borderline resistant” MIC’s to
3rd generation fluoroquinolones
 MRSA, MRSE, and Enterococcus emerging
resistance to vancomycin!
 Commercial poultry producers have the most
significant effects!!

Resistance To Fluoroquinolones

Oxazolindinones
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new class of antibiotics
IV, IM, PO
Linezolid (Zyvox/Pfizer)
 complicated
skin infections (MRSA)
 pneumonia (SA) - nosocomial
 pneumonia (streptococcus pneumoniae)
 bacteremia (Vancomycin resistant Enterococcus)
New Fluoroquinolones
Grepafloxacin (Raxar) - P.O.
 Levofloxacin (Levaquin) - P.O. / IV
 Sparfloxacin (Zagam) - P.O.

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Zagam RespiPac
Trovafloxacin (Trovan) - P.O.
 Alatrofloxacin (Trovan) - IV
 Gatifloxacin (Tequin)
 Moxifloxacin (Avelox) - P.O.

The Evolution of Quinolones
Nalidixic
Acid
Limited
spectrum
of activity
Norfloxacin
Lomefloxacin
Ciprofloxacin
Ofloxacin
Sparfloxacin
Grepafloxacin
Levofloxacin
Extended spectrum
Enhanced activity against
gram-negatives
Gatifloxacin
Moxifloxacin
Extended spectrum
Enhanced activity against
gram-positives and
anaerobes
Improved pharmacokinetics
New Fluoroquinolones for 2003
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Act on DNA gyrase & Topo-isomerase
More effective against gram positives including
streptococcus
Maintains activity against Pseudomonas
Highly soluble
Favorable kill curve kinetics
Favorable pharmacodynamics
Active against FQ resistant organisms
Pediatric indication down to age 1
Comparative Antimicrobial Issues-2005
Fluoroquinolone penetration pharmacokinetics into
aqueous humor
 Threat of atypical mycobacteria
 Comparison of fungal contamination in BAK preserved
and BAK-free fluoroquinolone antibiotics
 Corneal epithelial cell integrity

JAM
Potency of Moxifloxacin
Endophthalmitis isolates (98 isolates) Mather,
Kowalski et al AJO April 2002

Gram-positives
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Gram-negatives
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
moxi=gati=cipro=levo>oflox
FQ resistant Staph aureus
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moxi>gati>cipro=levo>oflox
moxi>gati>levo>cipro=oflox
FQ resistant Staph epi
–
moxi=gati>levo=cipro=oflox
Potency of Fluoroquinolones
Mather et al, AJO, 2002
MIC's of Fluoroquinolones to 93 Endophthalmitis
Isolates
MIC
2.5
Staph epi
2
Staph aureus
1.5
Strep pneumo
Gram Negatives
1
0.5
0
oflox
cipro
levo
Antibiotic
gati
moxi
Antimicrobial Therapy – 2005

Expanded spectrum fluoroquinolones
–
Trovafloxacin (Trovan / Pfizer)
 Less soluble than levofloxacin or ofloxacin
 Superior to ciprofloxacin or ofloxacin in Staphylococcus
and Streptococcus keratitis
 Almost as good as vancomycin against Streptococcus
without the toxicity
 Comparable to ciprofloxacin for Pseudomonas
 ONE YEAR + until approval!
JAM
Antimicrobial Therapy - Oral

Penicillins
–
–

Dicloxacillin 500mg qid
Amoxicillin/Clav (Augmentin 500mg, 850mg bid, 1000mgXL
bid)
Cephalosporins
–
–
–
–
–
–
Cephalexin (Keflex 250mg qid)
Cefaclor (Ceclor 250mg tid)
Cefadroxil (Duracef 1000mg qd)
Cefixime (Suprax 400mg qd)
Cefprozil (Cefzil 500mg qd)
Ceftriaxone (Rocephin 1g IM)
JAM
Antimicrobial Therapy - Oral

Macrolide
–
–
–
–
Erythromycin Ethylsuccinate (EES 400mg qid)
Erythromycin Particles (PCE 333mg tid)
Erythromycin Delayed (ERYC 250mg qid)
Clarithromycin (Biaxin 250mg bid x 7 D) & Biaxin 500mg
XL Pac
–
Azithromycin (Zithromax Z-Pak, new Tri Pak)
 Z-Pak:
500mg qd-Day 1, 250mg qd-Day 2-5
 Tri Pak: 500mg X 3 Days
 12mg / kg / Day X 5 Days (Pediatric)
 ISV-401(InSight Vision) – 6 drops in 5 days; Phase II
JAM
Antiviral - Topical Therapy
Vidarabine (Vira - A)
 Trifluorodine (Viroptic)
 Treatment Considerations

–
–
–
–
Monotherapy
Debridment
Resistance
Adjunctive measures
Cidofavir (Vistide/Forvade)
 Acyclovir (Zovirax/Cream 5%) 5X/D x 4D
 Pencyclovir (Denavir/Cream 1%) 9X/D x 4D

JAM
Antiviral Therapy - Oral

Acyclovir (Zovirax 200/400/800mg)
–
–
–
–
Primary Herpes Simplex: 400mg- 5x/D x10D
Chronic Suppressive: 400mg bid qd
Varicella: 20mg/kg- 4x/D x 5D
Herpes Zoster: 800mg- 5x/D x 10D
Famciclovir (Famvir 500mg tid x 7D)
 Valacyclovir (Valtrex 1000mg tid x 7D)

JAM
Post-Herpetic Neuralgia

Incidence - 10% of all VZV patients
–
–
–

50% PHN > 50 years
75% PHN > 70 years
2% PHN lasts > 1 year
Treatment
–
–
–
–
Capsaicin (Zostrix 0.025%, 0.075%HP)
Amitriptyline (Elavil 75mg qd)
Gabapentin (Neurontin 600mg tid)
Nerve Blocks (Anesthesiology)
JAM
Antifungal Agents

Topical
–
–

Nystatin (Nystatin)
Natamycin (Natacin)
Systemic
–
–
–
–
Amphoteracin-B (Fungizone)
Ketoconazole (Nizoral)
Fluconazole (Diflucan)
Miconazole (Monistat)
JAM
Topical Hyperosmotic Agents

Sodium chloride
–
–
–
–
Solutions – 2%, 5%
Ointment 5%
Clinical applications – Fuch’s endothelial dystrophy, bullous
keratopathy, epithelial edema
Available as Muro #128, Adsorbonac 2%/5%, generics
JAM
Traumatic Corneal Abrasions

Methods (Donnenfeld/Ophthal 6/97)
–
–
–

Pressure Patch/Topical Antibiotic
Bandage SCL
Bandage SCL & Topical NSAID
Results
–
–
–
No difference in re-epithelialization time
Psychometric Analysis-Patients prefer Bandage SCL &
NSAID
Return to Normal Activities-1.37 days
JAM
NSAID / Analgesics - Topical
Diclofenac (Voltaren qid)
 Suprofen (Profenal q2h)
 Flubiprofen (Ocufen q 1/2h)
 Ketorolac (Acular qid, Acular PF, Acular LS)
 Non-Preserved Anesthetics
 Peroxicam (Feldene)
 Bromfenac (Xibrom) - Ista Pharmaceuticals/ phase III
for ocular inflammation following cataract surgery

–
1st bid drug
JAM
Analgesics (OTC) - Oral
Acetysalicylic Acid (ASA 325-650mg q4h)
 Acetyl -Para - Aminophenol (APAP 325-650mg q4h)
 Ibuprofen (Advil, Motrin, Nuprin 200-400mg q4h)
 Naproxen (Aleve 220-400mg q8-12h)
 Ketoprofen (Actron, Orudis - KT 12.5-25mg q4h)

JAM
NSAID - Oral

Propionic Acids
–
–
–
–
–
–
Ibuprofen (Motrin 300,400,600,800mg tid)
Naproxen (Naprosyn 250,375,500mg bid)
Naproxen (Anaprox 275,550mg bid)
Ketoprofen (Orudis 25,50,75mg qid)
Flurbiprofen (Ansaid 50,100mg qid)
Ketorolac (Toradol 10mg q4-6h)
JAM
NSAID - Oral

Acetic Acids
–
–
–
–

Indomethacin (Indocin 25,50,75mg tid)
Suldinac (Clinoril 200mg bid)
Tolmetin (Tolectin 200,400,600mg tid)
Diclofenac (Voltaren 25,50,75mg qid)
Opioid (?)
–
Tramadol (Ultram 50-100mg q6h)
JAM
NSAID - Oral

COX-2 Inhibitors
–
–
–
–
Celecoxib (Celebrex 200mg)
Rofecoxib (Vioxx 12.5, 25mg)
Valdecoxib (Bextra 10mg qd)
Meloxicam (Mobic 7.5mg, 15mg qd)
JAM
NSAID - Oral

Salicylates
–
–

Oxicams
–
–

Salsalate (Disalcid 500, 750mg qid)
Diflunisal (Dolobid 250,500mg bid)
Piroxicam (Feldene 10,20mg bid)
Oxaprozin (Daypro 600mg bid)
Fenamates
–
Meclofenamate (Meclomen 50,100mg tid)
JAM
Analgesics (Narcotic) - Oral

Codeine
–
–

APAP 300mg + CD 15,30,60mg (Tylenol #2, 3, 4 q4h)
ASA 325mg + CD 15,30 60mg (Empirin w/ codeine #2, 3, 4 q4h)
Hydrocodone
–
APAP 500mg + HC 2.5, 5, 7.5mg (Lortab q4h)
–
APAP 500mg + HC 5, 7.5 mg (Vicodin q4h)
JAM
Analgesics (Narcotic) - Oral

Oxycodone
–
–
–

APAP 325mg +OC 4.5mg (Percodan q4h)
APAP 325mg +OC 5mg (Percocet q4h)
APAP 500mg +OC 5mg (Tylox q6h)
Propoxyphene Napsylate
–
–
–
APAP 325mg +PN 50mg (Darvocet N-50 q4h)
APAP 650mg +PN 100mg (Darvocet N-100 q4h)
PHCL 65mg (Darvon q4h)
JAM
Alternative Treatments for Pain

Ibuprofen / Acetaminophen
–
–
–
–
–
Inexpensive
Non-prescription
Non-narcotic
Excellent synergism
Motrin 400-600mg/Acetaminophen 500-1000mg
 No
motrin in pregnancy
 No acetaminophen in alcohol abusers
JAM
Glaucoma Considerations

Glaucoma Diagnosis Has Changed!
– Central corneal pachymetry (CCT – OHTS)
– Short Wavelength Autoperimetry / Frequency Doubling
– Confocal Scanning Laser Tomography
– Ocular Blood Flow Modulation
– Neuroprotection of RGC
 Primary
injury - mechanical, genetic, vascular, metabolic
 Secondary injury - glutamate, nitric oxide, free radicals

Glaucoma Treatment Strategies Have Changed!
–
IOP Reduction / Safety / Optic Nerve Health
–
Medications / LTP / Trabeculectomy
JAM
Anti-Glaucoma Agents

Non-Selective B-Adrenergic Antagonists
–
–
–

Timolol (Timoptic 0.25%, 0.50%, XE, Istalol/Ista
Pharmaceuticals)
Levobunolol (Betagan 0.25%, 0.50%)
Metipranolol (Optipranolol 0.3%)
Selective B-Adrenergic Antagonists
–
–
–
Betaxolol (Betoptic-S 0.25%, 0.50%)
Levobetaxolol (Betaxon)
Carteolol (Ocupress 1.0%)
JAM
Anti-Glaucoma Agents

Prostaglandin Analogue
–
Latanoprost (Xalatan 0.005%)
 Switch
to monotherapy from inadequate control on timolol
 Switch to monotherapy as effective as adding dorzolamide
–
–
–
–

Latanoprost / Timolol (Xalcom)
Bimatoprost (Lumigan 0.03%)
Travoprost (Travatan 0.004%/ Extravan with timolol 0.5%)
Unoprostone (Rescula 0.15%)
Pipeline
–
DE-085 (Santen) prostaglandin based; phase II
JAM
Anti-Glaucoma Therapy

Adrenergic Agonists
–
–
–
–
Dipivefrin (Propine 0.1%)
Epinephrine (Epinal,Eppy-N, Epifrin, Glaucon)
Apraclonidine (Iopidine 0.5%, 1.0%)
Brimonidine (Alphagan 0.2%, Alphagan P) / Timolol
(Combigan)



41% less ocular allergy with Alphagan P vs Alphagan over 12 months
Only ophthalmic glaucoma drug without BAK
Cholinergic
–
Pilocarpine (Pilocar 0.50% - 8.0%, Pilogel 4%)
–
Carbachol (Carbachol 0.75%, 1.5%, 2.25%, 3%)
Echothiophate Iodide (0.03%, 0.06%, 0.125%, 0.25%)
–
JAM
Antiglaucoma - CAI

Topical
–
–
–

Dorzolamide (Trusopt)
Dorzolamide-Timolol (Cosopt)
Brinzolamide (Azopt)
Oral
–
–
–
Acetazolamide (Diamox)
Methazolamide (Neptazane, MZM)
Dichlorphenamide (Darinide)
JAM
Glaucoma Pipeline
Matrix metalloproteinases (MMP) / Extracellar matrix
 Oral neuroprotectants

–
Memantine (Allergan)
Endolaser CycloPhotocoagulation (ECP)
 AquaFlow Implant (Staar)
 Dynamic contour tonometry (DCT) – Pascal device
from Zeimer Ophthalmic

–
–
–
Force vs. Dynamic contour tonometry
Highly accurate
Independent of thickness or edema
JAM
Nutritionals
Ocuvite (B&L)
 Ocuvite extra (B&L)
 Ocuvite Lutein (B&L)
 Ocuvite PreserVision (B&L)

–
–
AREDS NIH Study
2 tabs bid
ICAPS Lutein & Zeaxanthin Formula (Alcon)
 ICAPS AREDS formula
 I-Sense OcuShield (Akorn)

JAM
Nutritionals

Ocuvite (B&L)
–
–
–

Ocuvite extra (B&L)
–
–
–

1000IU/200mg/60IU/2mg/40mg
General eye health along with multivitamin
1 tablet qd or bid
1000IU/300mg/100IU/2mg/40mg plus select B vitamins
General eye health for those not taking multivitamins
1 tablet qd or bid
Ocuvite Lutein (B&L)
–
–
–
No A/60mg/30IU/6mg/15mg
For those at risk for ARMD, smokers, high exposure to UV
1 capsule qd or bid
JAM
Nutritionals

PreserVision AREDS Tablets (B&L)
–
–
–
–

PreserVision AREDS Soft Gels (B&L)
–
–
–
–

Moderate to advanced ARMD
Can crush tablets
4 tablets daily: 2 in morning and 2 evening with meals
28,640IU/452mg/400IU/No Lutein/69.6mg = Daily dose
Moderate to advanced ARMD
For those with swallowing difficulties
2 soft gels daily: 1 in morning and 1 in evening with meals
28,640IU/452mg/400IU/No lutein/69.6mg = Daily dose
PreserVision Lutein Soft Gels (B&L)
–
–
–
For smokers, high UV exposure, difficulties swallowing
2 soft gels daily: 1 in morning and 1 in evening with meals
No A/452mg/400mg/10mg/69.6mg = daily dose
JAM
Photodynamic Therapy for CNV

Intravenous infusion of photosensitiser
– Verteporfin (Visudyne/Novartis)
–

tin ethyl etiopurpurin (SnET2/Miravant)
Photoactivation - low level non- thermal 689nm light
within 15min after starting 10min IV infusion
–
50j/cm2 of NV lesion @ 600mW over 83secs
Photodynamic Therapy for CNV

Treatment spot =1000u larger than the Greatest
Linear Dimension (GLD)
–
–
–
allows a 500u border
established by IVFA & color photography
measure all classic & occult NV, blood +/- blocked
fluorescence, serous detachment of RPE
 maximum
spot size = 6400u
 recheck every 3 months & retreat if any CNV
–
Averages 3.4 treatments / year x 1 year
 avoid
exposure to bright light x 5 days
Pipeline for CNV
Intravenous infusion of photosensitiser
– Antecortave (Retaane/Alcon)
 Vascular endothelial growth factor (VEGF/rhuFab
V2, Genentech)

–
–
Therapeutic antibody fragment that interfers/binds with
VEGF, a protein that plays a critical role in the formation
of new blood vessels.
New partnership between Novartis and genentech renames
rhuFab “Lucentis”
Pipeline for CNV

Retrobulbar injection - Antecortave (Retaane /Alcon)
Intravitreal implant – (Fluocinolone / Retisert)
 Intravitreal implant – (Dexamethasone / Posurdex)
 Intravitreal injection- (Pegaptanib / Macugen)

–
–
–
–
Selective VEGF antagonist for classic, occult, and mixed
forms on CNV
Intravitreal injection every six weeks
70% lost <3 lines (27% treatment effect for loss of 3 lines
or more). Less effect in second year
Complications include endophthalmitis, RD, cataract, IOP
spikes
Botulinum Toxins

Toxins type A to G
–
–

Blocks neuromuscular transmission by inhibiting the release
of presynaptic acetylcholine at peripheral neuromuscular
junctions
Local denervation produces paresis or paralysis with few
side effects, good duration of action
Approved for the treatment of focal muscle spastic
disorders and excessive muscle contractions, such as
dystonias, spasms, twitches, strabismus
Drugs That Affect The Cornea
Chloroquine/hydroxychloroquine – whorl like
epithelial opacities
 Crack cocaine – ulceration, epithelial defects
 Isotretinoin – corneal opacities, neaovascularization
 Amiodarone – whorl like epithelial opacities
 Gold salts – gold deposits in the stromal cornea
 Indomethacin – stromal opacities, whorl like
epithelial opacities
 Chlorpromazine – endothelial pigmentation

Drugs That Affect The Lens
Chlorpromazine – anterior subcapsular cataracts
 Gold salts – anterior subcapsular cataracts
 Corticosteroids – posterior subcapsular cataracts
 Amiodarone – anterior subcapsular cataracts
 Methoxysoralen – cataract
 Schizophrenia drugs – Mirapex, Requip cataracts

Drugs That Alter IOP

Increased IOP
–
–
–
–

Corticosteroids
Phenothiazines
TCAs
Antihistimines
Decreased IOP
–
–
–
–
B-blockers
Cannabinoids
Ethyl alcohol
Cardiac glycosides
Drugs That Affect Retinal Function








Chloroqiune –RPE changes, red color loss
Thioridizdine – RPE changes, VF loss
Talc – particles in the small arterioles of the retina
Tamoxifen – refractile opacities in the retina
Isotretinoin – impairment of dark adaptation
Niacin – cystoid macular edema
NSAIDs – retinaql hemorrhages
Oral contraceptives – vein occlusions, perivasculitis,
edema, hemorrhage
–

More common with diabetes, obesity, smoking, HTN, migraines,
phlebitis, hyperlipidemia
Interferon – cotton wool spots, CRAO, CRVO, macular
edema
Drugs That Affect Optic Nerve
Ethambutol – retrobulbar optic neuritis
 Chloramphenicol – optic neuritis
 Isoniazid – optic neuritis
 Oral contraceptives – pseudotumor cerebri
 Tamoxifen – optic neuritis
 Tetracycline – pseudotumor cerebri
 Amiodarone – papillitis
 NSAIDs – optic neuritis

Thank you
John A. McGreal, O.D.
Missouri Eye Associates
Excellence in Optometric Education
JAM