TD: Ophthalmic Lecture

Question 1

Name the following parts of the eye

Give a breif description of each

Answer 1

• A: Viterous humour
  
  • ​the transparent gelatinous tissue filling the eyeball behind the lens.
• B: Aqueous Humour
  
  • ​the clear fluid filling the space in the front of the eyeball between the lens and the cornea.
• C: Retina
  
  • ​a layer at the back of the eyeball that contains cells sensitive to light, which trigger nerve impulses that pass via the optic nerve to the brain, where a visual image is formed. (contains rods and cones that allow you to see)
• D: Iris
  
  • a flat, coloured, ring-shaped membrane behind the cornea of the eye, with an adjustable circular opening (pupil) in the centre (coloured part of the eye)
• E: Optic Nerve
  
  • ​transmitting impulses to the brain from the retina at the back of the eye.
• F: Sclera
  
  • ​the white outer layer of the eyeball. At the front of the eye it is continuous with the cornea.
• G: Cornea
  
  • ​the transparent layer forming the front of the eye - protects the eye
• H: Pupil
  
  • ​Pupils are the black center of the eye. Their function is to let in light and focus it on the retina (the nerve cells at the back of the eye) so you can see. Muscles located in your iris (the colored part of your eye) control each pupil.

Question 2

What is the eye?

How is the eye contected to the brain?

Answer 2

The eye is an outgrowth from the brain

Linked to the visual cortex at the bottom rear of the brain by the optic nerve

Question 3

What is the different between the aqueous humour and viterous humour?

What seperates these chambers?

Answer 3

Aqueous humour drains and is constantly replaced where as the viterous humour does not drain

The lens seperates both chambers

Question 4

Describe the structure of the cornea

Answer 4

The cornea is made of of several different layers and is structured lipotphillic/ hydrophillic/ lipophillic:

• Epithelium
• Bowman’s layer
• Stroma
• Descemet’s membrane
• Endothelium

As structured this way drugs which penetrate will need balance of solubility.

The outer layer contains tight cell junctions which open for charged molecules - large molecules therfore will not pass through.

It is composed of 75% water and there is no blood supply

Question 5

Describe drug delivery to the cornea

Answer 5

• Drugs can only pass if low MWT
• Cornea negatively charged at pH 7.4
• Local drug delivery only i.e must apply directly to the eye not orally

Question 6

Describe drug delivery to the retina

Answer 6

• Highly vascularised
• Delivery mainly by injection

Question 7

Describe drug delivery to the conjunctiva

Answer 7

• The white of the eye and inside of the eye lids
• Large surface area for absorption
• 10-100x more permeable than cornea
• helps to produce tear films

Question 8

Describe the layer of the tear duct and function

Answer 8

Lipid layer ontop of water layer prevents water evapporation. Glycoprotein in water layer and microvilli trap foreign particles e.g. drugs, eyelashes, dust and they end up washed away as fluid replaced every 10mins and by the blinking reflex.

Question 9

Complete the sentances regarding tearfilm/duct:

• Eye drop instillation causes
• Drug clearance via
• Dilutes
• Tear fluid buffers drug - affects of drug

Answer 9

Eye drop instillation causes tear drop production

Drug clearance via reflex blinking

Dilutes drug

Tear fluid buffers drug - affects ionisation of drug

—Mucus quickly produced then digested.

—Removes foreign bodies from the eye.

—Eye drop installation cause tear production.

—Drug clearance via reflex blinking.

—Drug binds to tear proteins.

—Dilutes drug.

—Tear fluid buffers drug – affects ionisation of the drug.

Question 10

Why is the eye so difficult to target?

Answer 10

• Blinking reflex – 20 min-1.
• Frequent Tear flow – 1 µl min-1.
  
  • Replaced every 10 mins
• Very hard outer layer.
• Cornea has no direct blood supply.
• Back of the eye is even more difficult to reach – BBB.

​

Question 11

What is bioavailablily like and why?

Answer 11

Poor - around 5%

• Due to all the protective mechanisms and tear turn over approx. every 10mins.
• Most product removed after 2-5 mins
• Eyeworks to maintain tear volume at approx 10uL but average eye dropper is 30um

Question 12

What are examples of common eye conditions?

Answer 12

• Dry eyes
  
  • Due to not blinking enough (e.g. sitting in front of computer screen) or damage to lipid layer of tear films so water is evapporating off
• Itchy or irritated eyes
  
  • Allergy or hayfever
• Glucoma
  
  • Raised intraoctular pressure in viterous humours which is putting pressure on optic nerve
• Cataracts
  
  • Opaqueness of the lens

Question 13

What are examples of ophthalmic products?

Answer 13

• Eye drops
• Eye gels
• Ointments
• Spray
• Insert

Question 14

What are the requirements for conventional eye drops?

Where is the drug absorbed?

Answer 14

• Largely composed of water
• Must be sterile
  
  • So made with WFI or irridated with gamma radiation
• Should be isotonic with neutral pH
  
  • To prevent water movement in the eye
• Drug absorbed through cornea or conjunctiva
• Systemic uptake very low

Question 15

What is an important counselling point for eye drops?

Answer 15

Don’t let eye dropper touch any part of eye as can introduce bacteria into the eye

Question 16

How can bioavailablility be improved?

Answer 16

Prolong drug action by:

1. Reducing drainage.
   
   • Viscosity enhancing agents.
     
     • Gels.
     • Ointments
     • Emulsions.
2. Enhancing corneal penetration.
   
   • Facilitated transport.
     
     • Penetration enhancers.
     • Prodrugs
     • Nanoparticles.

Question 17

Describe the use of viscosity enhancing agents

Answer 17

• Viscosity enhancing agents:
• Polymer gels such as carbomer, hydroxypropylcellulose and sodium hyaluronate act to increase contact time of the drug with the tissues.
• Optimum viscosity is 12-25mPa.s.
• Pseudoplastic rheology is perfect for ophthalmic delivery.
• In situ gels: become a gel on a reaction with the eye

Question 18

When should ointments be used?

How do they work?

What side effects can they have?

Answer 18

• Can blur vision so reccomended for bed time use
• Reduces drainge and dilution therefore stays on eye for longer and greater chance for absorption
• Side effects such as eye lids glued together or crusty eyes in morning

Question 19

What is an example of an emulsion used?

Why is this emulsion good?

Answer 19

• Restasis is a cationic liquid emulsion for dry eyes
• Positive compounds easier to absorb

Question 20

How do penetration enhancers work?

What are examples?

Answer 20

• Disrupt cells, causing tight junctions to open, allow drugs an easier route into the corneal tissues.
• Traditional penetration enhancers have a tendency to damage cells – Benzalkonium chloride and EDTA.
• Amphiphillic polymers may be a useful alternative – water and oil-loving, like biological membranes.

Question 21

What is an example of a prodrug used to increased corneal penetration?

Answer 21

• Diesterification of adrenalin (more lipophilic). Esterases within the cornea act to regenerate the adrenaline.
• Ten-fold increase in corneal absorption.

Question 22

How do nanoparticles increase corneal penetration and bioavailability?

Answer 22

• Large SA therefore improved absorption
• Eliminated slowly.
• Can be bioadhesive - therefore attach painlessly to eye for longer periods
• Paracellular and transcellular transport therefore through and inbetween cells

Question 23

Examples of less common

Answer 23

• Ocusert®: CR of pilocarpine for glaucoma (4-7 days).
  
  • Reduces systemic absorption.
• Lacrisert®: hydroxypropyl cellulose for dry eyes (24h).
  
  • No excipients or preservatives due to freeze-dried nature.
• iVation – titanium helical coil coated with triamcinolone acetonide (925 μg) and nonbiodegradable polymers - diabetic macular edema (2 years).
• Port drug delivery system (ForSight Vision 4) – ranibizumab (slow down the loss of vision in four different eye conditions: neovascular age-related macular degeneration (AMD); diabetic macular oedema (DME); macular oedema and pathologic myopia (4 months).

Question 24

Describe gene therapy

Answer 24

• Replacing faulty genes to treat disease.
• Inactive virus can deliver genes to cells.