Anterior tear layer Lipids
Middle tear layer 98% tear film; aqueous
Posterior layer Mixture of mucin
Cornea: epithelial layer Hydrophobic
Bowman’s layer Distinct layer of collagen fibers
Stromal layer Hydrophilic layer; 90% thickness
Descement’s membrane Basement membrane of corneal epithelium
Endothelium Monolayer of cells adhering together by tight junction;
hydrophobic layer
Drug absorption across cornea Hydrophobic-hydrophilic-hydrophobic
Anterior chamber 250 uL of aqueous humor
Aqueous humor Secreted by the ciliary process; flows from posterior chamber;
2 pathways
Conventional pathway 80-95%; main target of cholinergic drug for glaucoma
Uveoscleral pathway Target of selective prostanoids
Open angle glaucoma Clogged drainage hole
Close angle glaucoma Blocked drainage hole
Iris Drug binding is influenced by binding to melanocytes
Outer radial muscle Mydriasis
Inner circular muscle Miosis
Bright light Circular (contract); radial (relaxed); pupil (constricted)
Dim light Circular (relaxed); radial (contract); pupil (dilated)
Pupillary constriction (miosis) Parasympathetic; M3 cholinergic receptor
Pupillary dilation (mydriasis) Sympathetic; a1 adrenergic receptor
Ciliary body Production and secretion of aqueous humor; accommodation;
outer longitudinal, middle radial, and inner circular layers
Ciliary body parasympathetic effect Zonular fibers (relax); Lens (convex) - accomodation: allows
focusing near objects
Blocked by MUSCARINIC CHOLINERGIC ANTAGONIST
(through CYCLOPLEGIA)
Ciliary body contraction Puts traction on the scleral spur and hence widens the spaces
within the trabecular meshwork
Accounts for some of the IOP-lowering effect of directly acting
and indirectly acting parasympathomimetic drugs
Ciliary muscle relaxation B2 adrenergic receptor
Ciliary muscle accomodation M3 cholinergic receptor
Causes opacity of lens Aging; Corticosteroid; Diabetes
Drug delivery strategies Prolonging the time in the cul-de-sac beneath the eyelid
enhances drug absorption
Ophthalmic gels Released drugs by diffusion following erosion of soluble
polymers
Ointments Usually contain mineral oil and a petrolatum base and are
helpful in delivering
antibiotics, cycloplegic drugs, or miotic agents
Solid inserts Gancliclovir intravitreal implant, provide zero-order rate of
delivery by steady-state diffusion
Other variables specific to the eys 1. Routes of ocular drug administration
2. Flow of ocular fluids
3.Architecture of the eye
ABSORPTION
1. Time the drug remains in the cul-de-sac and precorneal tear
After topical instillation of a drug, the rate and extent of film
absorption are determined by 2. Elimination by nasolacrimal drainage
3. Drug binding to tear proteins
4. Drug metabolism by tear & tissue proteins
5. Diffusion across cornea & conjunctiva
DISTRIBUTION 1. Mydriatic effect of alpha adrenergic agonists slower in onset
Melanin binding of certain drugs - darkly pigments irides compared to those with lightly
pigmented irides
“Slower onset, longer duration of action in darkly pigmented
iris”
2, Accumulation of chloroquine in retinal pigment epithelium -
Bull’s eye maculopathy
METABOLISM 1. Dipivefrin hydrochloride - epinephrine
Esterases - particular interest 2. Latanoprost - prostaglandin F2A
Loteprednol - inactivated in the eye to prevent systemic effect
TOXICITY Hypersensitivity reactions or direct toxic effects on the cornea,
conjunctiva, periocular skin, and nasal mucosa
-most common local toxic effects
Dacryocystitis Infection of the lacrimal sac
Blepharitis Bilateral inflammatory process of the eyelids
Primary indications for the use of antiviral drugs 1, Viral keratitis
2. Herpes zoster ophthalmicus
3. Retinitis
Autonomic drugs 1. Used extensively for diagnostic and surgical purposes
2. Treatment of glaucoma, uveitis, and strabismus
Glaucoma Characterized by progressive loss of retinal nerve fiber layer
tissue and visual field loss
Glaucoma Characterized by progressive optic nerve cupping and visual
field loss
Glaucoma risk factors Increased IOP
Positive family history of glaucoma
African-American heritage
Possibly myopia
Diabetes
Hypertension
PG analogs Largely replaced adrenergic receptor antagonists as FIRST-
LINE therapy FOR GLAUCOMA
PG analogs 1.Latanoprost (Xalatan)
2.Travoprost (Travatan, Travatan Z)
3.Bimatoprost (Lumigan, Latisse)
PG analogs MOA Gq/11-PLC-IP3-Ca2+ pathwau\y - active in isolated in human
ciliary muscle cells
PG analogs LOWER IOP by 1. Altering ciliary muscle tension - RELAXATION
2. Loosen trabecular meshwork
Beta receptor antagonists NEXT COMMON topical medical treatment FOR GLAUCOMA
Nonselective Beta antagonist 1. Timolol maleate
2. Levobunolol
3. Metipranolol
4. Carteolol
Beta-selective antagonist Betaxolol
Topical carbonic anhydrase inhibitor FOR GLAUCOMA 1. Dorzolamide (Trusopt)
2. Brinzolamide (Azopt)
Carbonic anhydrase inhibitor MOA Work by inhibiting carbonic anhydrase (isoenzyme II), which is
found in the ciliary body epithelium. This
reduces the formation of bicarbonate ions, which reduces fluid
transport, and thus, IOP
Uveitis Inflammation of the uvea; has both infectious and non-
infectious causes
Tropical therapy FOR UVEITIS 1. Cyclopentolate
2. Tropicanamide
3. Longer-acting agents:
Atropine
Scopolamine
Homatropine
Strabismus Ocular misalignment; numerous causes; any age; causes
diplopia (double vision) or amblyopia (reduced vision)
Nonsurgical treatment FOR STRABISMUS Occlusion therapy, orthoptics, optical devices, and
pharmacological agents
Atropine (1%) Instilled in the preferred seeing eye produces cycloplegia and
the inability of this eye to accommodate, thus forcing child to
use the amblyopic eye
Echothiophate iodide Also have been used in the setting of accommodative
strabismus
Muscarinic cholinergic antagonists and sympathomimetic Frequently used singly or in combination for surgery and
agents diagnostic purposes
Edrophonium test Helpful in diagnosing MYASTHENIA GRAVIS
Trypan blue (visionblue) Marketed to facilitate VISUALIZATION OF THE LENS and for
staining during surgical VITRECTOMY PROCEDURES to
guide the excision of the tissue (MEMBRANEBLUE)
Glucocorticoids Used for managing ocular inflammatory diseases
Topical glucocorticoids 1. Dexamethasone
2. Prednisolone
3. Fluorometholone
4. Loteprednol
5. Rimexolone
6. Diflurednate
Topical glucocorticoids uses 1. Ocular allergy
2. Anterior uveitis
3. External eye inflammatory disease assoc w/ infections
4. Ocular cicatricial pemphigoid
5. Postoperative inflammation following retractive, corneal, and
intraocular surgery
SubTenon’s capsule injection Used to manage posterior uveitis
Intravitreal injection of steroids 1. Age-related macular degeneration (ARMD)
2. Diabetic retinopathy
3. Cystoid macular edema
Parenteral steroids followed by tapering oral doses Preferred treatment FOR OPTIC NEURITIS
Ophthalmic implant of Fluocinolone and Dexamethasone Marketed for treatment of CHRONIC, NON INFECTIOUS
UVEITIS
NSAIDs Supplied as solutions and suspension for topical ocular use to
reduce ocular inflammation and cystoid macular edema
Flurbiprofen Used to counter unwanted intraoperative miosis during cataract
surgery
Ketorolac Seasonal allergic conjuctivitis
WITH PHENYLPHRINE - added to intraoperative ophthalmic
irrigation solutions to decreases miosis during cataract surgery
Diclofenac used for postoperative inflammation and pain
Ketorolac and Diclofenac Effective in treating cystoid macula edema occuring after
cataract surgery and in controlling pain after corneal refractive
surgery
Bromfenac and Nepafenac For treating postoperative pain and inflammation after cataract
surgery
Pheniramine and Antazoline Both H1 receptor antagonists, are formulated in combination
with NAPHAZOLINE, a vascoconstrictor, for relief of allergic
conjuctivitis
Emedastine difumarate Also used as antihistamine and mast cell stabilizer
Cromolyn sodium Prevents the release of histamine and other autacoids from
mast cells for VERNAL CONJUNCTIVITIS
Povidone-iodine (5%) Use prior to surgery to prep periocular skin and irrigate ocular
surfaces, including the cornea, conjuctiva, and palpebran
fornices
Adjuncts in Anterior segment surgery Viscoelastic substances assist in ocular surgery by maintaining
spaces, moving tissue, and protecting surfaces
Viscoelastic substances are prepared from 1. Hyaluronate
2. Chondroitin sulfate
3. Hydroxyproplymethylcellulose
Anterior segments gases 1. Sulfur hexafluoride (SF6)
2. Perfluoropropane gases have long been used as vitreous
substitutes during retinal surgery
Verteporfin Approved FOR PHOTODYNAMIC THERAPY of the exudative
form of ARMD with predominantly classic choroidal
neovascular membranes
Topical anesthetic agents 1. Proparacaine and Tetracaine drops
2. Intanasal cocaine
3. Lidocaine
Proparacaine and Tetracaine drops Used topically to perform TONOMETRY, to remove foreign
bodies on the conjunctiva and cornea, to perform superficial
corneal surgery, and to manipulate the nasolacrimal canalicular
system
Intranasal cocaine Used intranasally in combination with topical anesthesia for
cannulating the nasolacrimal system
