Introduction

The eye is composed of a variety of tissues that vary greatly, and which organization is critical to vision. Thus, one drug’s positive effect on one tissue could negatively affect the neighboring tissue. Treatment strategies towards ocular disease can be especially challenging because some tissues are vascular while some are avascular, and because of the ocular barriers. The ocular barriers including the cornea and sclera and the blood-ocular barrier, composed of the blood-aqueous barrier at the iris and ciliary body, and the blood-retinal barrier at the choroid and retina, can make target tissues hard to reach in therapeutic levels. When choosing a proper ophthalmic treatment strategy, the practitioner must choose a drug and route of administration that allows the drug to penetrate into the target tissue, maintain therapeutic drug levels in the target tissue for a reasonable time, and that has the least severe adverse effects on the target tissue and systemically. The ocular surface facilitates local treatment of certain ophthalmic disease, enabling us to minimize systemic side effects and maximize concentration of medications in ocular tissues. Topically administered medication eventually enters the vascular system via the nasolacrimal system, conjunctiva, aqueous humor, and anterior uvea in minimal quantities and most often without systemic adverse effects. In general, ocular surface disease is most often amenable to topical treatment. However, not all eye disease can be treated via this route. Systemic administration of medication is typically most effective for treatment diseases in the eyelids, orbit, or posterior ocular segment. The conjunctiva and anterior uvea can be addressed both via the topical and systemic route.

Dos and Don’ts When Applying Topical Ophthalmic Drugs

• Always administer one drop
• Always leave at least 5–10 minutes between drops of a different type
• Always work to give the least viscous drug first and most viscous drug last
• Two (or more) ointments can be administered simultaneously
• Consider using drops for nasolacrimal intraluminal conditions
• Topical drugs should never be administered by subconjunctival injection
• Drugs required in high concentration in the cornea and conjunctiva are usually best administered by frequent topical application
• Drugs required in high concentration in vascular components of the eye usually are best administered by a systemic route
• Make sure the drug formulation used facilitates penetration into the target tissue. Many topically applied drugs do not cross the cornea and the blood-ocular barrier prevents many systemically administered drugs from reaching the aqueous or vitreous humors
• Posterior segment disease must be treated via the systemic route
• Do not use ointment formulations on deep ulcers or when a corneal rupture is present or prior to ocular surgery, or following intraocular surgery or if a bandage contact lens is placed as ointments should not enter the eye
• When no deep ulcers are present ointments can be used to increase contact time, provide lubrication, and protect against desiccation

Selected Topical Ophthalmic Drugs: Indications and Contraindications

Local Anesthetics (Proparacaine or Tetracaine Ophthalmic Solutions)

• Indications/effects:
• Corneal anesthesia for diagnostic and minor surgical purposes
• Contraindications/adverse effects:
• Not for repeated use. Inhibit corneal epithelialization, toxic to normal corneal epithelium, abolish protective reflexes and increase chance of further injury

Autonomic Drugs

Sympathomimetic Agents (Phenylephrine Ophthalmic Solutions)

• Indications/effects:
• Useful for localizing lesions with Homer’s syndrome, mydriasis
• Augmentation in dogs
• Contraindications/adverse effects:
• Can cause systemic vasoconstriction and cardiac arrhythmias

Parasympatholytic Agents (Atropine Ophthalmic Solution/Ointment, Tropicamide Ophthalmic Solution)

• Indications/effects:
• Mydriasis for short diagnostic purposes (tropicamide) or longer acting therapeutic (atropine) purposes, cycloplegia and pain relief (atropine), blood-aqueous barrier stabilization, prevent synechia formation
• Contraindications/adverse effects:
• Can increase intraocular pressure (avoid in glaucoma patients), decreases tear production (atropine, avoid in dry eye patients), hypersalivation and occasional vomiting (atropine, cats)

Direct-Acting Parasympathomimetic Agents (Pilocarpine Ophthalmic Solution)

• Indications/effects:
• To diagnose parasympathetic lesions, decreases IOP, neurogenic dry eye
• Contraindications/adverse effects:
• Miosis, inflammatory, less potent than other drugs for glaucoma treatment, systemic adverse effects (salivation, vomiting, diarrhea, and abdominal cramps)

Indirect-Acting Parasympathomimetic Agents (Demecarium Bromide Compounded Ophthalmic Solution)

• Indications/effects:
• Glaucoma prophylaxis in dogs, infrequent administration
• Contraindications/adverse effects:
• Miosis, less potent than other drugs for glaucoma treatment, irritation

Anti-Glaucoma Drugs

Prostaglandin Analogues (Latanoprost, Travoprost, or Bimatoprost Ophthalmic Solutions)

• Indications/effects:
• Potent intraocular pressure (IOP) reduction
• Contraindications/adverse effects:
• Contraindicated with anterior lens luxation, ineffective in cats and horses, mildly inflammatory, intense miosis

Carbonic Anhydrase Inhibitors (Dorzolamide or Brinzolamide Ophthalmic Solutions)

• Indications/effects:
• IOP reduction. Effective in dogs, cats, and horses
• Contraindications/adverse effects:
• Less potent than prostaglandin analogues, local irritation

Beta-Blockers (Timolol or Betaxolol Ophthalmic Solution)

• Indications/effects:
• Decreases IOP in horses and cats, glaucoma prophylaxis in dogs
• Contraindications/adverse effects:
• Bradycardia, less potent than other drugs for glaucoma (dogs), avoid in patients with respiratory or cardiac disease

Anti-Inflammatory Drugs

Corticosteroids (Dexamethasone Sodium Phosphate 0.1%, Prednisolone Acetate 1%)

• Indications/effects:
• Potent treatment of anterior segment inflammatory or suspected immune-mediated disease, decreases corneal vascularization and melanosis
• Acetates and alcohols are lipophilic and have good corneal penetration (i.e., can be used to treat of anterior uveitis), sodium phosphates have poorer corneal penetration
• Contraindications/adverse effects:
• Delays corneal wound healing, increases risk of infection and should be avoided with corneal ulceration or infection, can induce ocular feline herpes virus 1 reactivation in cats, may induce and/or exacerbate lipid +/- mineral degeneration of the cornea (steroid keratopathy) with chronic use, combination formulations with antibiotics should be avoided for chronic use to reduce risk of development of bacterial resistance, frequent/long-term administration may disrupt diabetes mellitus management or cause reversible adrenocortical suppression

Non-Steroidal Anti-Inflammatory Drugs (Flurbiprofen, Diclofenac, Nepafenac)

• Indications/effects:
• Good anti-inflammatory choice for diabetic patients, less likely to inhibit corneal healing than corticosteroids, potent
• Contraindications/adverse effects:
• Less potent anti­inflammatory than corticosteroids, can increase IOP, associated with corneal melting in humans

Immunosuppressant Drugs

Calcineurin-Inhibitors (Cyclosporine, Tacrolimus, Pimecrolimus)

• Indications/effects:
• Keratoconjunctivitis sicca (KCS), chronic superficial keratitis, eosinophilic keratoconjunctivitis and other immune-mediated surface diseases, decreases corneal vascularization and melanosis. Tacrolimus and pimecrolimus may be effective in KCS cases where cyclosporine is ineffective
• Contraindications/adverse effects/disadvantages:
• Poor intraocular penetration (ineffective for uveitis), irritation, besides Optimmune (cyclosporine 0.2%) these medications must be compounded, concerns about carcinogenic potential