by Noelle La Croix, DVM, Dip. ACVO
Ocular Steroidal Medications
There are many different formulations of ocular steroidal medications. This article will highlight some of the important aspects of the relationship between steroidal medications and the eye. The appropriate choice and usage of ocular steroids is affected by their pharmacodynamics.
Steroids that affect the eye are instilled as eye drops (solutions or suspensions), applied topically as ointments, or taken orally. Drops and ointments will produce higher concentrations of steroids within the anterior chamber of the eye than oral drugs. However, drops and ointments have been found to solely treat intraocular inflammation confined to the anterior chamber. In studies utilizing radioactive cortisone acetate, the highest concentrations of the steroid were found in the cornea and aqueous humour. Considerably lower concentrations of the steroid were found in the iris and no measurable quantity was found in the lens, vitreous, or retina. Treatments combining drops or ointments with oral steroids are therefore often necessary. For example in cases of uveitis, drops or ointments treat anterior segment inflammation while oral steroids combat inflammation within the ciliary body and posterior segment.
Drops and ointments must first cross the lipid-rich (hydrophobic) corneal epithelium to penetrate deeper tissues of the eye. The corneal epithelium prevents the ingress of polar hydrophilic compounds (e.g. prednisolone phosphate) but allows lipophilic compounds (e.g. alcohol form of dexamethasone and the acetate form of prednisolone) to pass freely. Externally applied treatments for intraocular inflammation, that are commercially available, include 1% prednisolone acetate, and neomycin/polymyxin/dexamethasone (neo/poly/dex). Note that 1% prednisolone acetate is thought to achieve a higher intraocular concentration, and therefore produce a greater anti-inflammatory effect, than the dexamethasone of neo/poly/dex.
In humans, concentrations of steroids within the aqueous humor rise for 15-30 minutes following drop instillation. Increasing an eye drop’s initial concentration at instillation will raise its subsequent aqueous humor concentration. However, concentrations greater than 1% (e.g. prednisolone acetate) do not appear to provide higher efficacy in the treatment of ocular inflammation.
Steroids in microsuspensions, gels, or viscous formulations increase their contact time with ocular surface. Many of these products can therefore achieve twice the aqueous humor concentrations of their equally concentrated eye drop counterparts. Prednisolone acetate and neo-poly-dex are available as microsuspensions (Figure 1). These suspensions must be shaken vigorously prior to application. Unshaken, less than 30% of the maximum dosage is applied. Commercial formulations can also affect the dosage achieved by similarly concentrated steroidal microsuspensions. For example, one recent study found that a microsuspension of 1% prednisolone acetate from one source delivered 82% of the steroid while another delivered only 22%. This discrepancy often necessitates brand-specific prescriptions.
Some ointment formulations can decrease the intraocular penetration of a steroid. For example, the intraocular penetration of neo/poly/dex ointment is only 75% of its microsuspension counterpart. The decreased penetration may be secondary to an increased affinity of the hydrophobic dexamethasone alcohol to other hydrophobic ointment components rather than the hydrophilic tear film. Topical ointments are generally more appropriate for combating surface and conjunctival inflammation, or can be used in cases where drop instillation is not feasible.
To combat ocular inflammation steroids must be frequently administered to the eye. In humans, uveitis is treated with steroid microsuspensions every 1-2 waking hours for 2 days, and 4 times daily thereafter. In veterinary patients compliance with a 1-2 hour drug regimen is difficult to achieve, but 4 times daily initial dosing should be minimal.
The properties of steroids, their formulations, and their adminstration affect their efficacy in combating ocular inflammation. A better understanding of steroid pharmacodynamics should help the clinician in choosing and prescribing these drugs. If you have further questions about ocular steroids, please contact your veterinary ophthalmologist.
Noelle La Croix, DVM, Dip. ACVO
Judy Seltzer, DVM, Dip. ACVD
The Veterinary Medical Center of Long Island
75 Sunrise Highway
West Islip, New York 11795
(631) 587-0800, fax (631) 587-2006