6Tc: Steroids

Mechanisms of Action of Topical Steroids

• Inhibition of Phospholipase A2: Reduces inflammation by decreasing the production of arachidonic acid, thereby inhibiting the production of prostaglandins.

• Effects on Cellular Activity:

  • Inhibit cellular migration

  • Stabilize mast cells, reducing histamine release

  • Decrease fibroblast proliferation

  • Reduce vasodilatation and edema

  • Prevent scar tissue formation

Steroids and Their Functions

• Produced by the adrenal cortex:

  • Glucocorticoids: Involved in glucose, protein, and bone metabolism; exhibit anti-inflammatory effects.

  • Mineralocorticoids: Maintain electrolyte balance.

  • Sex Hormones: Hormones related to reproduction.

• Natural Glucocorticoids: Corticosterone, hydrocortisone (Na retention creating water retention).

• Synthetic Steroids: Developed to be potent anti-inflammatories with lower Na retention.

Corticosteroid Actions

• Suppress inflammation, not a cure; prevents scarring and vascularization in ocular structures.

• inhibit most aspects of the inflammatory response

• Timelines of Action:

  • Early stage: Reduces heat, swelling, pain, and redness.

  • Late stage: Can inhibit wound healing and repair.

  • anti-inflammatory action: very valuable but hazardous

Uses of Corticosteroids in Ocular Disorders

• Commonly prescribed for a range of acute ocular inflammatory disorders such as:

  • Viral Keratoconjunctivitis (VKC)

  • Chemical burns

  • Post-keratoplasty conditions

  • Anterior and posterior uveitis

• Preferred usage: Topical therapy to avoid systemic side effects associated with oral steroids.

General Principles of Corticosteroid Use

• Treatment Initiation: Start as soon as indicated.

• Dosage Management: Must be adequate for inflammation suppression; frequent evaluation of dosage. Strong enough to suppress the inflammation.

• Tapering: Long-term treatments must be tapered after symptoms subside to prevent relapses.

  • the premature halting of treatment can lead to relapse. Often the second episode is worse than the first.

Important Guidelines for Optometrists

• Understanding immunological processes related to ocular inflammation:

  • immunological processes relevant to inflammatory conditions of the eye and their natural histories

  • Knowledge of typical presentations and differential diagnoses.

  • Immediate treatment for ocular emergencies.

  • Identification of risk factors and potential side effects, including increased intraocular pressure and cataract risk.

• Generally, optometrists will be using topical steroids for conditions that resolve in the short term. Expert opinion should be sought for long-term steroid use.

  • no repeats for steroids

  • In selecting a corticosteroid preparation, optometrists should select the preparation that is most likely to effectively treat the condition of the patient with the least propensity for side effects.

  • Topical steroid preparations with a propensity for intraocular penetration, such as dexamethasone and prednisolone, should not be used for conditions that are responsive to less readily absorbed steroids

Topical Ocular Corticosteroids

• Availability: Subject to prescription (S4) in Australia.

• Examples include:

  • Fluorometholone: (e.g., Flarex, Flucon)

  • Hydrocortisone: (e.g., Hycor)

  • Dexamethasone: (e.g., Maxidex)

  • Prednisolone: (e.g., Minims)

  • Prednefrin: Prednisolone Plus phenylephrine

Potency and Pharmacologic Comparisons

• Potency Ranking (weakest to strongest): FML < Flarex < Maxidex < Prednisolone < Prednefrine forte.

• Most potent: Dexamethasone (Maxidex) as it is produced in the lowest concentration (0.1%)

• high concentrations of a given agent are not more effective.

suspension = bottle must be shaken with use.

Fluorometholone (Flarex, FML)

• weakest steroid available.

• Action: Corticosteroid, relatively non-penetrating.

• Use: Indicated for steroid-responsive inflammatory ocular conditions.

• Contra/Caution: Use with caution in patients with:

  • Viral infections

  • Tuberculosis (TB)

  • Fungal infections

  • Prolonged use

  • Corneal thinning

  • Pregnancy

  • Children

• Adverse Effects:

  • Increased risk of glaucoma

  • Cataract formation

  • Risk of superinfection

  • Less increase in intraocular pressure (IOP) compared to other steroids.

• Pack:

  • 0.1% concentration, 5ml, in suspension form.

  • Must shake well before use; acetate version is more effective and metabolized slower than alcohol forms.

• Dose:

  • Administer 1-2 drops, 2-4 times per day.

  • If necessary, increase to 2 drops every 2 hours.

  • Gradual tapering is recommended, along with nasolacrimal occlusion techniques to minimize systemic absorption

Dexamethasone (Maxidex)

• Action: Corticosteroid, stronger than phosphate derivatives due to alcohol derivatives.

• Use: Indicated for intraocular inflammatory eye diseases.

• Contra/Caution: Use with caution in patients with infections, prolonged use, corneal thinning, pregnancy, and children.

• Adverse Effects: Includes glaucoma, cataract formation, risk of superinfection, and has the highest propensity to increase intraocular pressure (IOP).

• Pack: Available in 0.1% concentration, 5ml.

• Dose:

  • Severe: 1-2 drops every hour, decrease as inflammation subsides;

  • Mild: 1-2 drops every 4-6 hours, along with nasolacrimal occlusion, and taper as necessary.

Prednisolone (Prednefrin Forte)

Considered the most effective for anterior segment ocular inflammation.

• Action: strong corticosteroid, prednisolone acetate; considered the most effective anti-inflammatory agent for anterior segment ocular inflammation.

• Use: Severe inflammatory eye disease. Systemic: Oral forms available for asthma and chronic obstructive pulmonary disease (COPD).

• Contra/Caution: Use with caution in patients with infections, glaucoma, pregnancy, lactation, and children.

• Adverse Effects: Increased intraocular pressure (IOP), cataracts, and corneal thinning.

• Pack: Available in 1% concentration, 10ml.

• Dose: 2 drops every hour for 2 days, then 1-2 drops 2-4 times/day, tapering and using nasolacrimal occlusion as necessary.

Hydrocortisone (Hycor)

• Action: 1st corticosteroid discovered, largely superseded, topical skin treatment.

• Use: Inflammatory eye disease (including Herpes Zoster).

• Contra/Caution: Use with caution in patients with infections (TB, fungal, viral), corneal thinning, prolonged use, cataract, diabetes, glaucoma, pregnancy, and children under 2 years. Interacts with topical ophthalmic agents (use 10 minutes apart). Has marked mineralocorticoid properties, may cause sodium and water retention and potassium loss.

• Adverse Effects: Increased intraocular pressure (IOP), delayed healing, and cataracts.

• Pack: Available in 0.5%, 1%; drops 10 ml; ointment 5g.

• Dose: 2-4 times/day, with nasolacrimal occlusion and tapering as necessary.

Topical Steroid Monitoring

• need to monitor the:

  • Corneal epithelium

  • IOP

  • lens

  especially if used for >2 weeks.

Corticosteroid side effects

Corticosteroids & Cataracts

• tend to be bilateral and subcapsular

• Dose and duration specific

• systemic use carriers greater risk

• produces disulphide bonds and protein aggregation

• Termination of therapy halts progression, in few cases the size of the opacity decreases

• Children and diabetics are more susceptible.

Corticosteroids & IOP elevation

Individual variation in susceptibility exists, with 1-5% of people being steroid responders, and about 1/3rd of users showing a moderate increase in intraocular pressure (IOP).

• Duration and Dose: These factors are significant in IOP elevation, with a possible lag of 3-6 weeks after starting corticosteroid treatment.

• Drug Variation: Different steroids have varied effects; dexamethasone and betamethasone are known to be more problematic. Soft-steroids are less likely to cause IOP increases.

• Reversibility: Generally, IOP increases are reversible upon termination of treatment, although steroid-induced glaucoma may not respond to cessation of therapy.

• Mechanisms of IOP Increase: The increase in IOP may be due to:

  • Accumulation of abnormal collagen and/or basement membrane material in the trabecular meshwork.

  • Lamellar thickening around trabecular structures.

  • Decreased phagocytic capacity of the trabecular cells, which increases outflow resistance.

What to do if IOP rises

• tapering drug will usually decrease IOP

• Switch to new “soft steroid” - steroids with less impact on IOP

• Add a glaucoma drug if steroid use is continued: beta blocker and alpha agonist

Corticosteroids and infection

• Reduce bodies immunologic defence mechanisms

• Lower resistance to infection

• Mask symptoms of infective disease

• Exacerbation of existing bacterial & viral infections

• Severe aggravation of herpes simplex and fungal eye infections

• In ocular infection Tx, steroids can be beneficial to reduce inflammation and scarring

• Avoid if scarring not likely

• Must use with concurrent antibiotic/antiviral Tx if ulcer was infective

Other Corticosteroid Side Effects

• Ocular: Mydriasis, ptosis, keratitis, corneal thinning, scleral thinning, uveitis, transient ocular discomfort.

• Systemic: Electrolyte imbalance, weight gain, delayed wound healing, mood changes, muscle weakness / atrophy, risk of infections, osteoporosis.

• Monitor closely if used for longer than 2 weeks.

Contraindications and Drug Interactions

• Contraindicated in patients with conditions such as:

  • Glaucoma

  • Diabetes

  • Renal disease

  • Osteoporosis

  • Psychiatric disorders

• Careful consideration when combined with other medications, particularly anticoagulants.

Additional Notes on Sports Regulations

• Systemic corticosteroids are banned in sports; however, non-systemic preparations (including ophthalmic) are allowed with appropriate exemption registration.