1. Ocular allergies

Question 1

Who does ocular allergies affect?

Answer 1

• 20% of the UK population.
  *Especially in individuals suffereing from hay fever, asthma, other allergies
  *Children and young adults with family history of allergies are more prone
  *30% of children with allergic rhinitis also experience ocular symptoms

Question 2

What are the risk factors of ocular allergies?

Answer 2

1. Environmental changes - Pollen, mould
2. Climate change - increased levels of pollen, spring/summer seasons are becoming longer so exposed to pollen for longer
3. Urbanisation - higher air pollution and indoor allergens
4. Genetic predisposition - family history

Question 3

Why are the eyes prone to allergens?

Answer 3

1. Eyeball is constantly exposed to the environment
2. Conjunctiva is highly vascularised so more immune cells present
3. Conjunctiva has large surface area
4. Large number of specialised immune cells

Question 4

What are the symptoms of ocular allergies?

Answer 4

1. Itching
2. Redness
3. Watering

Question 5

What is the difference between infection and allergy?

Answer 5

Allergy = more itchy, sneezing, nasal congestion
Bacterial infection = sticky yellow discharge
Viral infection = similar to allergy but no sneezing, is contagious

Question 6

In what conditions does conjunctival irritation occur?

Answer 6

1. Allergies
2. Viral/fungal/bacterial infections
3. Chemical/Physical irritants
4. Dry eye disease
5. Contact lens use
6. Nasolacrimal duct obstruction
7. Blepharitis
8. Post surgery
9. Autoimmune conditions
10. Medication

Question 7

What is an allergy?

Answer 7

A type of hypersensitivity reaction

Question 8

What are the types of allergic conjunctivitis?

Answer 8

1. Seasonal allergic conjunctivitis (SAC) (pollen, trees, grass)
2. Perennial allergic conjunctivitis (PAC) (Dust mites, mold, pet dander)
3. Vernal keratoconjunctivitis (VKC)
4. Atopic keratoconjunctivitis (AKC) (Perennial, usually in people with eczema)

Question 9

What are the symptoms of vernal keratoconjunctivitis?

Answer 9

*severe itching
*photophobia
*papillae on upper eyelid
*punctate keratitis
*Horner trantas dots (around iris)
*Thick mucoid discharge

Question 10

What are the symptoms of atopic keratoconjunctivitis?

Answer 10

*severe itching
*photophobia
*papillae on upper eyelid
*punctate keratitis
*shield shaped cataracts
*clear, thin watery discharge
*deep corneal neovascularisation

Question 11

What are the mechanism, mediators, examples and onset of Type 1 hypersensitivity?

Answer 11

Mechanism = IgE
Mediators = Mast cells, histamine
Examples = allergic rhinitis, asthma
Onset = immediate

Question 12

What are the mechanism, mediators, examples and onset of Type 2 hypersensitivity?

Answer 12

Mechanism = IgG, IgM
Mediators = Complement, ADCC
Examples = autoimmune hemolytic anemia
Onset = mins to hours

Question 13

What are the mechanism, mediators, examples and onset of Type 3 hypersensitivity?

Answer 13

Mechanism = Immune complex deposition IgG, IgM
Mediators = Complement, neutrophils
Examples = Rheumatoid arthritis, serum sickness
Onset = 3-8 hours

Question 14

What are the mechanism, mediators, examples and onset of Type 4 hypersensitivity?

Answer 14

Mechanism = T cell, neurophils, macrophages
Mediators = Cytokines, interleukins, prostaglandins
Examples = contact dermititis, herpes simplex virus keratitis, stroma keratitis, uveitis, giant papillary conjunctivitis
Onset = 48 -72 hours

Question 15

How is an allergic response produced?

Answer 15

Type 1 hypersensitivity accounts for 95% of all hypersensitivity reactions.

Mechanism of Type 1:

1. Initial sensitisation -
   Allergen enters body and binds to antigen presenting cell. This then binds to Th2 cells, causing activation of B cell. B cell produces IgE antibodies. IgE binds to FcER receptor on mast cell. This causes sensitisation and body will be able to recognise the allergen, resulting in immune reaction.
2. Subsequent exposure -
   Due to inital sensitisation, IgE receptors are ready to recognise allergen and start cascade of events. This causes influx of Ca2+ destabilising the mast cell. Mast cell breaks down, releasing histamine. Histamine binds to receptors causing: redness (vasodilation), oedema (vasodilation and leakage), itching, pain, tearing and mucin secretion. Itching causes a viscious cycle as you itch causing greater release of chemicals, worsening the symptoms.

Question 16

How do histamine receptors mediate their effects?

Answer 16

By coupling to G protein coupled receptor Q. Gq activates the enzyme phospholipase C, this increases IP3. Binding of IP3 to it’s receptor increases release of Ca2+, which mediates vasodilation and itching.

Question 17

Describe the histamine receptors

Answer 17

H1,H2,H3,H4 - These are G protein coupled receptors present in conjunctival epithelial cells and goblet cells.
H1 and H4 are more relevant to the eye.

Question 18

Where is H1 receptor found and what is it’s response?

Answer 18

Found on smooth muscle and blood vessels. Response is contraction, vasodilation, vascular permeability and histamine release.

Question 19

Where is H4 receptor found and what is it’s response?

Answer 19

Found on immunomodulatory cells. Response is mast cell chemotaxis (movement) and mast cell degranulation (release of chemicals).

Question 20

Describe mechanism of Type 4 hypersensitivity

Answer 20

1. cell mediated so the cells involved are: T cells, neurophils, and macrophages
2. The chemical mediators include: cytokines, interleukins, prostaglandins. (All produce inflammatory response)
3. The antigen presented in localised tissue/organ
4. It’s onset is delayed. Takes 48-72 hours for the inflammatory cells to infiltrate area and increase in number.

Question 21

Describe the strategy for management of allergies

Answer 21

Mild:
*Cold compress
*Oral antihistamines
*Astringent eye wash/drop

Moderate:
*Ocular decongestants (vasoconstrictor)
*Antihistamines
*Mast cell stabilisers

Severe:
*Ocular corticosteroids

Question 22

How do astringent eye washes/drops work?

Answer 22

Provide temporary relief by washing the allergen from the eye. Good to tell px to keep doors and windows closed at peak pollen times and to have air purifier.

These drops do contain Witch hazel (hamamelis) and benzalkonium chloride

Question 23

How do ocular decongestants work?

Answer 23

These are vasoconstrictors which slows down the release of chemical mediators, like histamines, to the conjunctiva from the blood stream. This counteracts the vasodilation, redness, oedema caused by chemical mediators. Works via sympathetic branch on alpha 1 adrenoreceptor.

They are compatible with antihistamines and other ocular drugs.

Question 24

Describe the availability of Ocular decongestants and the side effects.

Answer 24

Dilute solution of adrenaline. Synthetic derivatives:
*Oxymetazoline HCl
*Naphazoline HCl

Duration of action depends on the ingredients.
Available as P medicine.

Local effects:
*Transient stinging and blurring
*dilation of pupil - risk of acute angle closure glaucoma
*Rebound congestion - blood vessels can get leaky

Sytemic effects:
*Minimal due to conc and dosage but because of action through alpha 1 receptors on blood vessels, this could lead to high blood pressure and cardiovascular problems

Question 25

How does topical antihistamines work?

Answer 25

They are H1 receptor antagonists. They block histamine binding to receptor and thus preventing response triggered by mast cell. Redness, oedema, itchiness, pain, mucus is reduced. If there is no complete relief this is due to other H receptors and chemical mediators being invovled.

Question 26

Describe the availability of topical antihistamines and side effects.

Answer 26

1. Ketotifen - POM - 1 drop 2x daily for 4 months - 3 years old 2. Olopatadine - POM - 1 drop 2x daily - 3 years old 3. Antazoline - P - 1 drop 2-3x daily for 7 days - 12 years old 4. Azelastine - POM - 1 drop 2-4x daily for 6 weeks - SAC 4 years old, PAC 12 years old 5. Epinastine - POM - 1 drop 2x daily for 8 weeks - 12 years old - can only be prescribed by independent prescribers as its not on the additional supply list. Local side effects: *Transient stinging and blurring *Mydriasis *Contains benzalkonium chloride *Doesn't prevent histamine release so symptoms can come back

Question 27

How does mast stabilisers work?

Answer 27

They stabilise mast cells by binding to IgE receptors. This inhibits the influx of Ca2+ ions across the membrane. This prevents the degranulation of mast cell stopping the release of histamine and other chemical mediators from the mast cells.

Question 28

Describe the availability of mast stabilisers and side effects.

Answer 28

Adviced for Px to take these a week before symptoms start and in combination with antihistamines due to delay of relief with mast stabilisers. And will need to be taken continuously throughout allergy season. 1. Sodium cromoglicate - 1 drop 2-3x daily 2. Lodoxamide - 1 drop 4x daily for 4 weeks - 4 years old 3. Nedocromil - 1 drop 2-4x daily - 6 years old Legal status depends on drug and indication. GSL or P for SAC and PAC. POM for VKC and AKC. Local effects: *Transient stinging *Contains benzalkonium chloride

Question 29

Describe the availability of oral antihistamines and side effects.

Answer 29

If the symptoms are purely ocular then topical should be used as these drugs are taken in tablet or liquid form and won't effectively cross the retinal blood barrier. Everyone's allergy is different so response to drugs would be different. To determine the best way to manage you need to determine the type, and severity of symptoms. Mostly used for SAC and PAC. Drug taken 2-4x daily. Drugs differ in age ranges and in maximal duration of treatment. Systemic side effects: *Cardiovascular effects due to prevention of dialtion and increased permeability of small blood vessels *Smooth muscle effects due to prevention of stimulation of exocrine glands to produce secretions (salivary, gastric, lacrimal, bronchial) *Immune effects due to binding to histamine receptor and precenting histamine eliciting a response. Ocular side effects: *antimuscarinic effects and antihistamine effects can cause dry eye.

Question 30

How does the mechanism of dual action of Ketotifen and Olopatadine work?

Answer 30

In addition to antihistamine effects, they are both lipophilic and cationic compounds which disrupt Ca2+ influx. They either: *Insert into membrane and cause positive charge at the surface. This repels Ca2+ ions and prevents binding, effecting Ca2+ influx. This stabilises mast cell. or *Inserts into membrane and stablilises FCeR1 receptor. This repels Ca2+ ions and prevents binding, effecting Ca2+ influx. This stabilises mast cell.