ROUTES OF DRUG

ADMINISTRATION IN
OPHTHALMOLOGY
DR. JOSEPH KWARTENG
SPECIALIST OPHTHALMOLOGIST
KATH
INTRODUCTION

• Drugs can be administered to ocular tissue by various routes, which include:

Local:
1. Topical administration: Eyedrops, Gels, Ointments
2. Periocular administration: Subconjunctival, Sub-Tenon’s, Peribulbar, Retrobulbar
3. Intraocular administration: Intracameral, Intravitreal
Systemic:
4. Oral
5. Parenteral routes
The most appropriate method depends on the part of the eye to be treated
• The conjunctiva, cornea, anterior chamber and iris usually respond well to
topical therapy and periocular administration such as subconjunctival and
sub-tenon injection
• The eyelids can be treated with topical therapy but more frequently
requires systemic therapy
• The posterior segment requires local and/or systemic therapy because most
topical drugs do not penetrate the posterior segment
• Retrobulbar and orbital tissues are treated systematically
TOPICAL
 TOPICAL

• Most favored route of ocular drug administration especially when targeting the
ocular surface and anterior segment diseases.
• Maximizes the anterior segment concentrations while minimizing systemic
toxicity.
• Drug solutions and suspensions as eye drops are applied topically by instillation
on the ocular surface e.g antibiotic, corticosteroids and antiglaucoma eyedrops
• Nb! Don’t let bottle spout touch eyelashes. Also, keep the bottle cap from getting
contaminated
• Gels and ointments are also popular dosage forms for topical drug administration,
commonly used for antibiotics and corticosteroids.
• They improve ocular absorption through prolonged retention in the cul-de-sac
• Causes blurring of vision and hence usually given at night
• Inserts placed in the fornices (eg ocusert for delivery of pilocarpine) and other drug
impregnated devices such as contact lenses applied to ocular surface are also the means
of topical drug delivery.
• Instillation of eye drops is the most convenient, least invasive and least expensive
method of drug administration to the eye.
 TOPICAL

• Has the advantage of avoiding systemic exposure to high serum levels of drug
• For example, systemic use of ganciclovir is associated with hematologic toxicity but
topically applied gel provides high ocular tissue concentration and is highly effective
against herpetic keratitis without significant risk of hematologic toxicity.
• provides inadequate drug concentration in the treatment of posterior segment diseases,
especially in the uninflamed eye.
PERIOCULAR INJECTIONS

• Periocular route of administration is used to inject drugs in the vicinity

of the globe without penetrating it.
• The drug bypasses the conjunctival and corneal epithelial barriers and
absorb passively down a concentration gradient into the sclera and
intraocular tissues.
• This approach is especially useful for drugs with low lipid solubility
(such as penicillin), which do not penetrate the eye adequately if they are
given topically.
• Subconjunctival, sub-tenon’s, peribulbar and retrobulbar injections
 SUBCONJUNCTIVAL INJECTION
• Used for ocular delivery of drugs that penetrate cornea poorly or are slowly
absorbed.
• Provides significantly higher ocular tissue concentration as compared to systemic
route of administration.
• An example is subconjunctival injection of 5-fluorouracil after trabeculectomy.
• Disadvantages include irritation and pain at the site of injection, subconjunctival
hemorrhage, granuloma, necrosis and conjunctival scarring.
• Inadvertent globe penetration and intraocular administration is also a concern.
 SUBTENON’S INJECTION
• Provides high intraocular drug levels by exploiting the permeability of sclera.
• Injection can be made in sub-tenon’s space in anterior, mid and posterior positions using
cannulae with increasing length
• Commonly used route of administration of local anesthetics for ophthalmic surgery
• Another example is posterior sub-tenon injections of steroids for cystoid macular edema
(CME)
• Complications associated with sub-Tenon’s injection include pain on injection, swelling,
pseudoptosis and subconjunctival hemorrhage.
• Ocular penetration and inadvertent intraarterial injections can result in severe
complications such as central retinal arterial occlusion and retinal and choroidal vascular
occlusion
 RETROBULBAR INJECTIONS
• Delivers drugs behind the globe inside the muscle cone
• Most common and serious complication of retrobulbar injection is retrobulbar
hemorrhage
• Another example is retrobulbar injection of 50-100% alcohol or chlorpromazine in
treatment of painful blind eyes
• Optic atrophy can occur due to direct damage to optic nerve or nerve compression due to
injection of drug solution inside the meningeal covering of the nerve.
• Others are stimulation of oculocardiac reflex, puncture of globe, inadvertent intravascular
and subdural injection and brain stem anesthesia.
 PERIBULBAR INJECTION
• Mainly used for injecting local anesthetic agents for surgical procedures
• For injecting drugs like triamcinolone acetonide in conditions such as diabetic
macular edema and Graves ophthalmopathy
• Can cause periorbital ecchymosis and conjunctival chemosis
• Incidence of retrobulbar hemorrhage, optic nerve injury, and inadvertent
intraocular or subdural injection is less as compared to retrobulbar injection.
 INTRAOCULAR
• Intraocular routes of drug administration, require drug administration inside the globe.
• The intraocular injection of drugs instantly delivers effective concentrations at the target site.
• Although this route may reduce systemic adverse effects, ocular adverse effects may be more
pronounced.
 INTRACAMERAL INJECTION

• Intracameral – “into a chamber”

• Used for purposes of pupillary dilatation and anesthesia for surgical procedures,
prevention of intraocular infection and inflammation
• Provides immediate and easy delivery of required concentration of drug into the
aqueous humor and, therefore, provides high efficacy.
• Moreover, the need for repeated administration, as is necessary if using topical
route, is avoided, which is especially a concern in non-compliant patients.
• The corneal surface toxicity associated with topical application is also avoided.
 INTRACAMERAL INJECTION

• Intracameral administration of medications, however, predisposes to toxic

anterior segment syndrome (TASS)
• Presence of free radicals in the intracameral solutions seems to contribute
to endothelial toxicity leading to corneal edema
• Examples include balanced salt solution, carbachol, tryphan blue and
preservative free lidocaine in intraocular surgeries
 INTRAVITREAL INJECTION

• For intravitreal administration, drug solutions are injected directly into the vitreous humor.
• This route of drug administration provides high drug concentration in the posterior segment of
eye and is used in the treatment of conditions like endophthalmitis, age-related macular edema,
CNV and diabetic retinopathy.
• The medications can also be delivered intravitreally in the form of implants that provide
sustained drug delivery over a prolonged period.
• This route of administration is especially useful for posterior segment drug delivery as other
routes of administration provide insufficient drug concentration in posterior segment.
• Examples are anti-VEGFs like bevacizumab (Avastin) and ranibizumab (Lucentis), ganciclovir
injection or implant, silicone oil, corticosteroids and various antibiotics
 SYSTEMIC
• DRUGS WITH HIGHER LIPID SOLUBILITIES MORE READILY PENETRATE THE BLOOD–OCULAR
BARRIER.
• Thus, chloramphenicol, which is highly lipid-soluble, penetrates 20 times better than does penicillin, which
has poor lipid solubility.
 ORAL
• Although a convenient method for drug administration, it suffers from several
disadvantages such as
• slow onset of action, poor absorption of highly polar drugs from gastrointestinal mucosa,
destruction by enzymes in gut, first-pass metabolism, uncooperative/unconscious patients or
patients suffering from gastrointestinal conditions like vomiting, diarrhea or other pathologies.

• Even if the sufficient amount of drug is absorbed into the systemic circulation it may
not be able to penetrate into the ocular tissue due to blood ocular barrier.
• Examples include oral diamox for increased IOP, oral steroids for
posterior/panuveitis, oral antibiotics for preseptal/orbital cellulitis, dacrocystitis and
hordeolum-
 PARENTERAL

• Intramuscular injections are made into the deltoid or gluteus muscles while
intravenous injections are given in the veins, mainly the antecubital vein.
• The parenteral injections require aseptic conditions, may be painful and besides
causing local complications expose the body to high concentrations of drugs.
• Drugs have to pass through the blood-ocular barriers and, therefore, may not reach in
sufficient concentration in the eye, but the risk of systemic adverse effects increases.
• Examples include administration of IV antibiotics in treating orbital cellulitis, IV
Methylprednisolone in Grave’s orbitopathy and botulin toxin injection in facial
dystonia
WHAT ARE THE DIFFERENT METHODS OF DRUG
ADMINISTRATION FOR THE TREATMENT OF EYE
DISEASE?
THANK YOU