7. Clinical Anti-inflammatories

Question 1

Name the 7 anti-inflammatories in Australia.

Answer 1

• Astringents
• Anti-histamines
• Mast cell stabilisers
• Dual action MCS/ AH
• NSAIDS
• Corticosteriods
• Calcineurin/ T cell inhibitor

Question 2

What are the 3 different formulations of topical anti-inflammatories? What makes them different?

Answer 2

• Multi-use eyedrops - perserved, usually with BAK → AH, MCS, MCS/AH, NSAIDs

• Single use eyedrops - non-preserved → lubricants, phenylephrine, ketotifen, flubiprofen, prednisolone phosphate

• Ointments - non-preserved, typically used for skin conditions areound the ocular areas → lubricants, hydrocortisone

Question 3

What are the indications for ocular lubricants?

Answer 3

For mild, non-specific inflmamation; mild ocular surface irritation (SPK), dry eye, neurotrophic keratitis; adjunct in severe inflammation

Question 4

What are the indication for astingents?

Answer 4

Mucoid discharge in allergic surface disease. Not used commonly in Australia.

Question 5

What are the indications for anti-histamines, mast cell stabiliser and dual action MCS/ AH?

Answer 5

MCS and AH usedful in eye disease with type I hypersensitivity (allergy)

Anti-histamines are H1 antagonists → will not reudce redness, effective at reducing itching

MCS takes times to control symptoms (reduce release of histamines), therefore should add topical steroids to control intial symptoms.

Question 6

What are the properties and indications for NSAIDS?

Answer 6

NSAIDS are anti-inflammatory, anti-pyretic and analgesic. They are used in mild/ moderate allergic eye disease (seasonal allergic conjunctivits) and other surface inflammation
e.g. episcleritis; intra-operative inhibition of miosis; post-operative inflammation (cystoid macular oedema)/ analgeia; post refractive surgery (photophobia/ pain)

Question 7

What are the indicaitons for corticosteroids?

Answer 7

Moderate to severe ocular surface inflammation; HSV and HZO keratitis (not epithelial), anterior uveitis; endophthalmitis (intravitreal). Any inflammation with type IV hypersensitivity component may require steriods.

Question 8

What are the indications for cyclosporine?

Answer 8

• Corneal graft
• Uveitis
• Scelritis
• Vernal keratoconjunctivitis
• Dry eyes

Question 9

Steroids/ ... block ... activity, which inhibits ... synthesis. Steroids also decrease ... production, which decrease ..., prevent ..., and also deregulate ... expression. Steroids also inhibit inflammaton, wihch therefore inhibits ..., decrease ... and .... In appearance, this can reduce .... The use of steriods can ....

Answer 9

Steroids/ glucocorticoids block phospholipase A2 activity, which inhibits prostaglandin synthesis. Steroids also decrease inflammatory cytokine production, which decrease cellular response and macrophage activation, prevent mast cell degranulation , and also deregulate cellular DNA expression. Steroids also inhibit inflammaton, wihch therefore inhibits vasodilation, decrease vascular permeability and scar formation. In appearance, this can reduce redness of the eyes. The use of steriods can suppress adrenal secretions of steriods.

Question 10

What are the treatment goals of steroids? How should we go abouts with the management?

Answer 10

Goal of using steroids is to rapidly control inflammation in order to minimse complications with the disease and also with the use of steroids. This is to prevent structral changes, scarring, and functional changes to the tissues. Short term or long term adverse effects can occur with steroids. Steroids should only used in short term in order to prevent or reduce side effects and withdrawal symptoms.

Question 11

What are the possible complcations of inflammation? Give examples of diseases that can lead to the complication.

Answer 11

Inflammation may cause cell and tissue loss, such as bacterial keratitis and necrotic HSV keratitis. It can also cause scarring and loss of function, such as microbial keratitis, stromal HSV keratitis, synechiae in anteiror uveitis. It can lead to collateral ocular surface disturbance, such as giant papillary conjunctivitis and vernal keratoconjunctivitis.

Question 12

What are the possible steroid adverse effects with short term to medium term doses? (5 points)

Answer 12

• IOP spike
• Secondary/ reactivation of infection (fungal, protozoa, viral)
• Masking clinical signs (can misjudge infection progress and delay recovery)
• Delayed wound healing (block tissue contraction, prevent scar formation)
• Transient discomfort

Question 13

What are the possible steroid adverse effects with long term doses? (3 points)

Answer 13

• IOP rise leading to steriod-induced glaucoma
• Posterior subcapsular cataract
• Systemic effects: weight gain, adrenal insufficiency, gernealised edema, Cushing syndrome, osteopenia, gastritis, avascular necrosis of femur head, excess body hair growth, premature closure of bony epiphysis etc.

Question 14

Rank the steroid potency in terms of drug type. [low to high]

Answer 14

Hydrocortisone → Flurometholone → Prednisolone

Question 15

Rank the steroid potency in terms of formulation. [low to high]. Why does changing formulation matter?

Answer 15

Sodium phosphate < Alcohol < < Acetate.
Changing the solubility and penetrance of steriods in order to suit where the drug should act.
E.g. Fluorometholone has poor corneal penetration itself, therefore good for surface diseases;
Adding acetate to fluorometholone (Fluorometholone acetate) allows for high corneal penetration, allowing high activity at the anterior chamber.

Question 16

Rank the steroid potency in terms of formulation. [low to high]

Answer 16

QID → Q2h → Q1h

Question 17

How do you select potency of topical steriods?

Answer 17

High potency and high penetration steriods are used for anteiror uveitis, which has to cross over the cornea in order to take effect in the uvea. It has the highest bioavailability intraocularly. Prednisolone acetate is the strongest formulation.

Low potency and low penetration steriods are used for mild surface inflammation, which has a lower chance of steriod-induced IOP rise. Fluorometholone has poor corneal penetration but high bioavailability at the cornea.

Question 18

Prednisolone is a ..., ... - based .... It is highly efficacious but also a high propensity to .... It is available in .... This is often used to manage severe inflammation, such as ....

Answer 18

Prednisolone is a high potency, ketone - based corticosteroid. It is highly efficacious but also a high propensity to raise intraocular pressure. It is available in different bases and concentrations. This is often used to manage severe inflammation, such as uveitis.

Question 19

Fluorometholone (FML) is a .... It is relatively ... compared to prednisolone. It also has a relatively lower ..., therefore making it a better option for .... It is available in ... and ... derivatives. This is often used in the management of ....

Answer 19

Fluorometholone (FML) is a moderate strength glucocorticoid. It is relatively less potent and less effective at controlling inflammation compared to prednisolone. It also has a relatively lower propensity to raise intraocular pressure, therefore making it a better option for longer term administration. It is available in acetate and alcohol derivatives. This is often used in the management of anterior inflammation.

Question 20

Dexamethasone is a .... It has the greatest potential to ... out of all steroids. It is used to manage ocular .... This is not available in Australia.
Hydrocortisone is a .... It is only used ....
Soft steriods are ...with .... This is because they can be ..., thus eliminate .... They are highly effective .... They also have the benefit of reducing the chance of ....

Answer 20

Dexamethasone is a high potency glucocorticoid. It has the greatest potential to increase intraocular pressure out of all steroids. It is used to manage ocular systemic inflammation. This is not available in Australia.
Hydrocortisone is a low potency corticosteroid. It is only used dermatologically.
Soft steriods are high potency steriods with extra margin of safety. This is because they can be rapidly metabolised, thus eliminate side effects. They are highly effective anti-inflammatories. They also have the benefit of reducing the chance of increase IOP.

Question 21

• For dermatological and ..., ... treatment should be used.
• To target iris or ..., treatment should have better ... with ... administration.
• For deeper than ..., ...injections should be used.
• For post-operative ... (CMO), ... should be used in order to ....

Answer 21

• For dermatological and anterior segment inflammation, topical treatment should be used.
• To target iris or anterior ciliary body inflammation, treatment should have better corneal penetration with more frequent administration.
• For deeper than anterior ciliary body, oral, intraocular, subconjunctival, sub-Tenon injections should be used.
• For post-operative cystoid macular oedema (CMO), topical NSAIDs should be used in order to inhibit production of prostaglandins in the anteiror eye.

Question 22

Bioavailability is the .... Bioavailability ... after instillation, due to the tear film. The average drop siz is ..., whereas the average tear volume is ..., hence the eye .... The concentration of drug is .... In order to achieve suffient bioavailability in the anterior chamber, we will require ..., therefore a ... frequency. Effectiveness is ....

Answer 22

Bioavailability is the volume of drug in a particular location. Bioavailability decreases immediately after instillation, due to the tear film. The average drop siz is 50 μL, whereas the average tear volume is 30 μL, hence the eye rapidly drains off the excess. The concentration of drug is linear and dose dependent. In order to achieve suffient bioavailability in the anterior chamber, we will require a higher bioavailability in the cornea, therefore a higher topical administration frequency. Effectiveness is dose dependent.

Question 23

Dosage of a drug should be sufficient to .... The dosage prescribed must be .... Long-term, high dosage therapy should ..., instead it should be .... Standard topical therapy will often require .... Short-term, low dose therapy ....

Answer 23

Dosage of a drug should be sufficient to sufficient to control inflammation and continue for as long as necessary. The dosage prescribed must be re-evaluated at regular intervals. Long-term, high dosage therapy should not be stopped abruptly, instead it should be tapered over a long period. Standard topical therapy will often require tapering over days or weeks. Short-term, low dose therapy does not require tapering.

Question 24

Why do we have to taper steriod therapies?

Answer 24

The use of synthetic steriods lowers the physiological levels of serum cortisol. Low serum cortisol will delay the body responses and cause rebound inflammation. We should taper the use of steriods to allow sufficient time for serum cortisol to return to normal ranges. Tapering approach is empirical and dependent on px responses.

Question 25

What is pulse dosing? What sort of eye conditions is pulse dosing good for?

Answer 25

Pulse dosing is administered in high doses and short bursts. It is used to achieve higher therapeutic effect initially and can be removed quickly, therefore doesnt require tapering. Pulse dosing can be done systematically or topically. Pulse dosing can be used for allergic or contact conjunctivitis.

Question 26

How can you achieve ocular pulse dosing? What are the benefits?

Answer 26

Increase frequency of dosing in order to increase bioavailability. Achieves faster inflammation control and reduce duration of side effects. Short term use with immediate withdrawal gives minimal predisposition to rebound effects. Effective for allergic or traumatic iritis (type I & IV hypersensitivity) . Also useful for dry eyes, adenovirus, SAS, GPC.

Question 27

With the use of topical steroid, ... are essential. If follow ups are not possible, .... ... should be monitored at all follow visits. ... should also be monitored, such as ..., ..., or ...

Answer 27

With the use of topical steroid, frequent follow ups are essential. If follow ups are not possible, we should reconsider the treatment strategy. Treatment effectiveness and progress should be monitored at all follow visits. Adverse drug reactions should also be monitored, such as IOP, cataract, or delayed wound healing

Question 28

Name the 3 immunomodulatory anti-inflammatories used in Australia. How do they act?

Answer 28

Restasis → Cyclosporin A 0.05% emulsion, act as calcineurin inhibitor and act on T cells in tear film, conjunctiva, and cornea. Increases tear production, therefore can be used for dry eyes

Cequa → Cyclosporin 0.09% solution

Xiidra → Lifitegrast 5% solution. Inhibits T-cell mediated inflammation.

Question 29

How many Australian optometrists are therapeutically endorsed? What are the most common drug prescriptions?

Answer 29

68% of Australian optometrists are therpeutically endorsed. Glaucoma and steroid preparations are the most common drugs prescribed (Most common drug = Latanaprost (Xalatan) > Fluorometholone (FML) > Prednisolone acetate w phenylephrine (Prednefrin Forte) > Fluorometholone acetate (Flarex))