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The Application of Topical, Injection, and
Oral Corticosteroids in Ocular Disease Management

Lorne B. Yudcovitch OD, MS, FAAO

 

Contents

Introduction

Many ocular and systemic conditions recognized by optometrists can be treated by the judicious use of corticosteroids, commonly known as steroids.  This course serves to educate the reader about the mechanisms of steroid action, potential ocular side effects and systemic effects.  It also provides information on indications and contraindications for use of steroids in optometric practice. 

Mechanism of Action of Steroids

In the mid 1800s, Addison and Brown-Sequard studied the role of adrenal glands in regulating body function.  Later, in the early 1900s, several hormones termed glucocorticoids and mineralocorticoids were isolated from the cortex of the adrenal gland.  The most important glucocorticoid derived from the adrenal gland is cortisol (sometimes called hydroxycortisone).

The mid-1900s brought the discovery of the interesting link between the adrenal glands, the pituitary gland (responsible for secreting adrenocorticotropic hormone, or ACTH, which stimulates adrenal cortex steroid production), and the hypothalamus (responsible for secreting corticotropin-releasing factor, or CRF, which stimulates pituitary ACTH production).  The hypothalamus secretes more CRF in response to neural excitatory stimuli and reduced plasma corticosteroid concentration.  This cascades to increasing pituitary ACTH production that ultimately increases adrenal cortex steroid production.  This interdependent feedback mechanism is termed the H-P-A axis (Figure 1).

Figure 1. H-P-A (Hypothalamus-Pituitary-Adrenal Cortex) Axis

 

What is the benefit of this H-P-A axis?  Simply put, it controls adaptation by the body to changing internal and external stimuli regulating corticosteroid secretion.  The corticosteroids affect the body in many complex ways, some of which are shown in Table 1.

 

EFFECT

 

MECHANISM

Anti-inflammatory
  • Reduce T cells and B cells responsible for inflammatory response
  • Inhibit macrophage and neutrophil migration
  • Inhibit prostaglandin synthesis by inhibition of phospholipase A(Z)

Hyperglycemia
  • Increase liver glycogen storage
  • Inhibit glucose oxidation
  • Increase insulin resistance by cell

Alteration of Lipid distribution

  • Increase fat deposits on face/neck (‘Cushingoid’)
  • Decrease fat from extremities
  • Increase lipid production from protein
  • Increase in low-density lipoproteins (LDLs)
  • -decrease in high-density lipoproteins (HDLs)

Blood cell constituents
  • Iincrease red blood cell and polymorphonuclear leukocyte number
  • Decrease eosinophils, basophils, and monocytes

Central nervous system
  • Various mood changes (unknown mechanism)

Allergic Response
  • Rreduce symptoms (unknown mechanism)

Table 1. Some corticosteroid effects on the body

 

In a normal individual, the adrenal glands normally secrete about 25mg of cortisol (hydrocortisone) and 5 mg corticosterone per day.  Only about 5% of these steroids are biologically active, the remainder being bound to plasma protein.  It is remarkable that such a small amount of active steroid can so dramatically modulate numerous metabolic activities.  Because the natural steroids are so potent and affect so many systems, the use of synthetic steroids in clinical practice should be done conservatively.

The main use of steroids in practice is to reduce inflammatory action.  Figure 2 displays the cellular synthesis of prostaglandins and leukotrienes from arachidonic acid.  This synthesis is termed the inflammatory pathway, and is the main cascade to the inflammatory response:

Figure 2. The inflammatory pathway and its inhibition by steroids and non-steroidal anti-inflammatory drugs.

The synthesis products of prostaglandins (particularly PGE(1), PGE(Z), and PGF(Z-ALPHA)) and leukotrienes have been implicated in inflammatory responses such as vascular dilation and polymorphonuclear leukocyte migration, but their exact mechanisms of action are still not well understood.  Steroids (specifically glucocorticosteroids such as cortisol or prednisone) reduce prostaglandin and leukotriene production by inhibiting the enzyme phospholipase A2, which converts phospholipids into arachidonic acid. 

As a side note, non-steroidal anti-inflammatory drugs (NSAIDs), such as indole derivatives (e.g.,indomethacin), pyrazolon derivatives (e.g., phenylbutazone), propionic acids (e.g., flurbiprofen), and the fenamates (e.g.,mefenamic acid) inhibit the enzyme cyclo-oxygenase from producing prostaglandins further along in the inflammatory pathway.  Because steroids block the inflammatory pathway at a higher level, it makes sense that they are generally superior to NSAIDs in reducing inflammation.

Steroids Commonly Used in Clinical Practice

Several steroids have been made synthetically for clinical use.  Table 2 shows the relative anti-inflammatory potencies of various corticosteroids, with hydrocortisone used as the standard with a value of 1.0.

 

 

 

CORTICOSTEROID

RELATIVE ANTI-INFLAMMATORY EQUIVALENT DOSE (mg)

 

 

 

 

RELATIVE POTENCY

Cortisone

25

0.8

Hydrocortisone

20

1

Prednisone

5

4

Prednisolone

5

4

Triamcinolone

4

5

Methylprednisone

4

5

Dexamethasone

0.75

25

Betamethasone

0.75

25

Table 2.  Anti-inflammatory potencies of various corticosteroids relative to hydrocortisone (source: Jaanus SD, Cheetham JK, Lesher GA.  Antiinflammatory Drugs in Bartlett JD & Jaanus SD. Clinical Ocular Pharmacology (4th Edition) 2001 Butterworth-Heinemann Chapter 12)

The effect of reducing inflammation depends heavily on the type and dosage of steroid used.  The most common steroid used by practitioners for oral use is prednisone.  It is available in tablet (1, 2.5, 5, 10, 20 mg amounts) and syrup forms (5, 6.7 and 15mg/mL concentrations).

 Figure 3.  Prednisone tablets (left) and syrup (image from MyAsthmaCentral.com website http://www.healthcentral.com/asthma/)

Besides the oral route of administration, steroids can also be inhaled (such as in certain inhalers for asthma treatment), injected either locally or intravenously (IV), and applied by the topical administration.  Table 3 shows some commercially available injectable steroids and their typical route of administration.  Table 4 lists the current commercially available topical steroids.

CORTICOSTEROID

TRADE NAME

ADMINISTRATION ROUTE

 

Methylprednisolone

Depo-Medrol

 

Solu-Medrol

IV, retrobulbar, transeptal

IV, subconjunctival/

tenons

Dexamethasone

Decadron-LA

 

Decadron Phosphate

IV, subconj/tenons, transeptal

Retrobulbar, intravitreal

Betamethasone

Celestone

Subconj/tenons, transeptal

Hydrocortisone (various forms)

Various

IV, topical, subconj/tenons

Triamcinolone

Aristocort, Kenalog

Subconj/tenons, transeptal, intravitreal

Table 3. Some commercially available injectable steroids and their typical administration routes

 

TOPICAL OCULAR STEROID

 

TRADE NAME

CONCENTRATION/

FORMULATION

Prednisolone acetate

Pred Forte (Allergan)

Econopred Plus (Alcon)

AK-Tate (Akorn)

Pred Mild (Allergan)

Econopred (Alcon)

1.0% suspension

1.0% suspension

1.0% suspension

0.125% suspension

0.125% suspension

Prednisolone sodium phosphate

Inflamase Forte (CIBA)

Metreton (Schering)

Inflamase Mild (CIBA)

AK-Pred (Akorn)

1.0% solution

0.5% solution

0.125% solution

0.125% solution

Dexamethasone alcohol

Maxidex (Alcon), others

Tobradex (Alcon)

0.1% susp, ointment

0.1% susp, ointment

Fluorometholone acetate

Flarex (Alcon)

Eflone

0.1% suspension

0.1% suspension

Fluorometholone alcohol

FML (Allergan)

FluorOp

FML-Mild (Allergan)

0.1% suspension

0.1% ointment

0.25% suspension

Rimexolone   

Vexol (Alcon)

1% suspension

Medrysone alcohol

HMS (Allergan)

1.0% suspension

Lotoprednol etabonate

Lotemax (Bausch & Lomb)

Alrex (Bausch & Lomb)

Zylet (Bausch & Lomb)

0.5% suspension

 

0.2% suspension

0.5% suspension

Table 4. Topical ocular steroids, listed from most potent (top) to least potent (bottom)

 

              Figure 4.  Various steroids used in eye care.  Pred Forte (prednisolone acetate 1%) suspension (left) is a commonly prescribed ophthalmic suspension.  Hydrocortisone 1% cream (middle) is often available over-the-counter. Kenalog (triamcinolone acetate) suspension (right) must be injected in-office.

Note that most topical steroids (except for sodium phosphate forms of Prednisolone) are in suspension form.  This requires that the patient shake the bottle to evenly distribute the steroid before instilling on the eye.  Also of note, acetate forms of steroids generally have the greatest anti-inflammatory property, followed by alcohol, then phosphate forms.  Hydrocortisone 1% ointment formulation, available over-the-counter but not available in ophthalmic formulation currently, is sometimes used for certain periocular skin conditions such as contact dermatitis.  Likewise, triamcinolone (Kenalog) dermatological cream (available in 0.025%, 0.1% and 0.5% concentrations) and other combination steroid/antibiotic ointments such as Maxidex, Tobradex, Vasocidin, Blephamide, Cetapred, and Pred-G, could be considered as alternative treatments.  However, the practitioner should always be aware if they are prescribing a drug in an off-label use.  Tobradex (tobramycin 0.3% antibiotic + dexamethasone 0.1% steroid) and Zylet (tobramycin 0.3% antibiotic + lotoprednol 0.5% steroid) are the two steroid-antibiotic combination ophthalmic suspensions prescribed currently.