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Duke Elder: Finals Ophthalmology (Alice) > Ocular therapeutics > Flashcards

Ocular therapeutics Flashcards

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1
Q

Label the following on the diagram of the eye: retina, vitreous, lens, cornea, pupil, iris, optic nerve

A

Label them all

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2
Q

Describe the path which light takes when entering the eye, to get to the posterior chamber/retina

A
  • Light passes through the clear cornea
  • Then passes through the anterior chamber which is filled with aqueous
  • Then through the lens into the posterior chamber which is filled with jelly-like vitreous
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3
Q

What are the 2 main layers that line the inside of the globe?

A
  1. Outside: sclera
  2. Immediately inside sclera: choroid (then inside this is retina)
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4
Q

What is the function of the choroid?

A

Vascular and provides nourishment

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5
Q

What are the 9 layers from the most superficial surface of the retina to the underlying choroid? Name in order

A
  1. Nerve fibre layer
  2. Ganglion cells
  3. Amacrine cells
  4. Bipolar cells
  5. Horizontal cells
  6. Photoreceptors (rods and cones)
  7. Retinal pigment epithelium (RPE)
  8. Bruch’s membrane
  9. Choroid
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6
Q

Identify the following layers of the neural retina on the diagram: inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer

A

Note cell bodies of amacrine cells, bipolar cells and horizontal cells are in inner nuclear layer. Bipolar cell axons are in the inner plexiform layer and dendrites are in the outer plexiform layer. The outer nuclear layer contains cell bodies of photoreceptors

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7
Q

What are 4 key barriers which prevent drug entry into the eye?

A
  1. Cornea
  2. Sclera
  3. Intraocular pressure
  4. Blood-ocular barrier
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8
Q

How does the cornea act as a barrier to drug entry to the eye?

A

Barrier against entry of anything into the eye including infections and drugs

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9
Q

How does the sclera act as a barrier to drug entry to the eye?

A

Prevents influx of some medications but more porous than the cornea

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10
Q

How does IOP act as a barrier to drug entry to the eye?

A

Needed to maintain the shape of the globe, any drug must work against pressure gradient to enter the eye

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11
Q

How does the blood-ocular barrier act as a barrier to drug entry to the eye?

A

Tight junctions that prevent entry of drugs into the eye from the bloodstream

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12
Q

What are the 3 layers that means that the cornea functions as a trilaminar permeability barrier to drugs?

A
  1. Epithelium
  2. Stroma
  3. Endothelium
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13
Q

How does the cornea epithleium act as a permeability barrier?

A

It is a layer of squamous, non-keratinised epithelial cells that is a barrier to hydrophilic molecules (difficult to pass through cell membranes of epithelial cells)

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14
Q

What is the structure of the cornea stroma and how does it act as a permeability barrier?

A
  • Composed of collagen fibrils
  • Hydrophilic molecules can pass through easily due to high water content, but barrier to hydrophobic molecules
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15
Q

What is the structure of the cornea endothelium and how does it act as a permeability barrier?

A
  • Thinnest layer: single layer of cells that line the inside of the cornea. Cellular layer
  • Barrier to hydrophilic molecules
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16
Q

How can the ability of drug molecules to penetrate the different layers of the cornea be summarised?

A
  • Normalised, hydrophobic molecules penetrate the epithelium/ endothelium
  • Ionised, hydrophilic molecules penetrate the stroma well
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17
Q

Indentify the different layers of the cornea on the histological image

A

Outermost of the curve (left hand side) is epithelial layer, red arrow points to stroma, innermost (longest arrow) is endothelium

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18
Q

How does the sclera prevent the influx of some medications?

A

Due to intraocular pressure, there is a constant outward flow across the sclera which drugs must over come

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19
Q

How do direct injections around the eye interact with the sclera?

A

Even these penetrate the sclera very slowly

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20
Q

Why is a blood-ocular barrier necessary and what is it analogous to?

A

The retina is a very sensitive and delicate structure which must be protected from infection, inflammation and toxins in the blood. Analogous to blood-brain barrier

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21
Q

What does the blood-ocular barrier consist of and what are the 4 locations?

A

Tight junctions between:

  1. the cells of the outermost layer of the retina, the retinal pigment epithelium (RPE)
  2. layers of the ciliary body
  3. pigmented and non-pigmented ciliary epithelium
  4. retinal capillary endothelial cells
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22
Q

What is the ultimate result of the blood-ocular barrier?

A

Prevents entry of substances into the posterior segment, which protects the retina and forms a barrier to prevent drug entry

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23
Q

What are 4 overall routes of ocular drug administration?

A
  1. Topical
  2. Periocular injections
  3. Intraocular injections
  4. Systemic (oral and IV)
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24
Q

What are 2 formulations of topical ocular drugs?

A
  1. Ointment
  2. Drops
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25
What are 3 types of periocular injections?
1. Peribulbar 2. Sub-tenon 3. Subconjunctival
26
Label the following on the diagram: conjunctiva, sclera, Tenon's capsule, sub Tenon's space
27
What is the prefix of eyedrop drugs and why?
G. e.g. G. chloramphenicol, for 'Guttae' which means drops in Latin
28
What is the most common route of administration for ocular therapies?
eye drops
29
What are 2 advantages of eye drops as a route of drug administration?
1. Minimises systemic absorption 2. Easy to use for majority of patients
30
What are 3 disadvantages of eye drops as a route of drug administration?
1. Natural tear flow means drops have a short period of contact with the eye 2. Permability of the eye: limits choice of molecules that can be used, difficult to penetrate the eye further than the lens 3. Less than 10% of an eye drop is absorbed into the eye
31
How does tear volume impact the administration of a drug with eye drops?
The average size of a drop administered from a container is about 35µl but tear film can only hold 7µl, so spillover of drops is to be expected
32
Why is a greater drop volume for eyedrops or greater number of drops unnecessary?
They will spill over (too large for tear film volume) and be of no additional benefit as the eye can't even hold one whole drop. A second drop will **wash out any previous drops.**
33
How long should be left between administration of multiple different eye drops and why?
At least 5 minutes, as administering them too soon will wash out previous drops due to the low volume of the tear film (7µl)
34
What has been developed to try and overcome issues of tear turnover and eye drops?
Paraffin-based ointments
35
What is the prefix of topic ointments for eye medications?
Oculatum e.g. Oc. Chloramphenicol
36
What is the key advantage of ointment over eye drops?
Increases drug contact time
37
What are 3 key disadvantages of ointment topical medications and what can be done to counter the second?
1. Can blur vision 2. Reduce penetration of other eyedrops - should therefore be administered last 3. Slow release of active drug may result in sub-therapeutic levels (exist as nano-crystals, only released when ointment melts)
38
How can systemic side effects occur from topical eye ointments?
Tears and drugs flow into the nasal mucosa, leading to absorption by the richly vascular nasal mucosa directly into the bloodstream, avoiding first pass metabolism
39
What are three advantages of subconjunctival injections?
1. Provides a high sustained dose for a number of hours 2. Can inject a good volume of fluid, acts as a depot for the drug to be released 3. Avoids cornea and conjunctival barriers allowing penetration into the posterior segment
40
What potential barrier to drugs does a subconjunctival injections face?
Has to pass through sclera against intraocular pressure to enter eye (despite bypassing cornea and conjunctiva)
41
What happens during a subconjunctival injection?
* Small bleb of drug injected under the conjunctiva * Conjunctiva is clear so needle can be visualised throughout its passage and inadvertent intraocular injection is unlikely * This provides a high dose for a few hours
42
What type of drug are subconjunctival injections often used to administer?
**Anti-inflammatory** and **antibiotic** injections *post-cataract surgery*
43
What makes the periocular and sub-Tenon's injections different?
Shape of needles used: Sub-tenon's is a curved, blunt cannula while peribulbar is a straight sharp needle
44
What type of injection for ocular medication is shown in the image?
Subconjunctival injection
45
Where is a peribulbar injection given?
Around the eye; needle passed through eyelid and into orbit but doesn't enter muscle cone, so conjunctiva not manipulated
46
What type of medications are peribulbar injections often used for?
Anaesthetic agents
47
What type of needle is used for a peribulbar injection?
Straight, sharp needle
48
What are the risks associated with a peribulbar injection?
May increase risk of inadvertent globe perforation
49
What is an advantage of peribulbar injections over subconjunctival injections?
Conjunctiva not manipulated so more suitable for surgery where it's important to keep the conjucntiva intact
50
What is an advantage of peribulbar injections over sub-tenons injections?
Peribulbar may be more effective at preventing movement of the eye (akinesia) than sub-tenons
51
What are sub-tenons injections used for? 2 key things
1. Anaesthetic for ocular surgery 2. Steroid injections
52
What is the needle like for sub-tenons injections and what is the advantage of this?
Blunt, curved needle so less chance of **globe perforation**
53
What does a sub-tenons injection involve?
Injection around the globe; small hole made in conjunctiva and underlying connective tissue, known as tenon's capsule. Blunt needle passed into sub-tenon's space and injection performed
54
What type of injection is shown in the image?
Sub-tenon's injection
55
What type of injection is shown in the image?
Peribulbar injection (note it's given into peribulbar fat)
56
What are the advantages of intravitreal injections?
Circumvents forces/ barriers to drugs entering the eye, as is injected directly through the sclera and into the vitreous cavity (posterior segment)
57
What are 2 things intra-vitreal injections are commonly used for?
1. anti-VEGF treatment for wet ARMD 2. anti-VEGF treatment for diabetic retinopathy
58
Why is it useful to use intra-vitreal injections to give anti-VEGF treatment?
Allows the agent to have direct access to the retina
59
What are 2 key risks of intra-vitreal injections?
1. Intraocular bleeding 2. Infection (endophthalmitis)
60
Why is there a particular risk of injection/endophthalmitis with intra-vitreal injections?
There are no blood vessels in the vitreous cavity so the immune system finds it difficult to identify and eliminate any infection
61
What are 3 key groups of drugs used in the eye clinic?
1. Topical anaesthetics 2. Vital dyes (e.g. fluorescein) 3. Dilating drops
62
What are 3 key uses for topical anaesthetics in the eye clinic?
Allows examination techniques that 'touch' the eye: 1. Applanation tonometry (measuring pressure) 2. Vital dyes 3. Diagnostic contact lens use
63
What are 3 commonly used topical anaesthetics in the eye clinic?
1. Proxymethocaine 2. Oxybuprocaine 3. Tetracaine
64
How do topical anaesthetics used in the eye clinic work?
Reversible block of conduction through nerve fibres by blocking axonal membrane sodium channels
65
What is the key vital dye used in the eye clinic?
Fluorescein
66
How does fluorescein work?
It is an orange-coloured dye that emits green light when blue light is shone on it; this shows areas of **devitalised epithelium** e.g. due to corneal ulceration or abrasion
67
What are 2 ways in which fluorescein can be used in the eye clinic?
1. Systemically: in fundus fluorescein angiography (FFA) to allow visualisation of retinal blood flow. Inject IV then flows into blood vessels of eye via heart 2. Topically: apply as a drop then examine under cobalt blue light for corneal abrasion/ ulceration/ herpetic eye disease
68
What are dilating drops used for in the eye clinic?
Used to dilate the pupil and examine the posterior segment/ retina
69
How long do dilating drops take to work and how long do they last for?
Take 30 minutes to work, can last for 6-8 hours
70
What is the small risk associated with dilating eye drops and who is most at risk of this?
Precipitating angle-closure glaucoma; most common in patients who are elderly or extremely long-sighted
71
What are the 2 main types of dilating eye drops and the way in which they work?
1. Anti-parasympathetic i.e. **anti-muscarinic**: reduce pupil constriction 2. **Sympathomimetics**: active pupil dilation
72
What is the most commonly used sympathomimetic for dilating the pupil and what type of drug is it?
**Phenylephrine**: alpha-1 agonist
73
What are the 2 types of phenylephrine preparations?
2.5% and 10%
74
How long does mydriasis take to occur after using phenylephrine dilating drops and how long does this last?
Onset 30-60 minutes, duration 4 hours
75
What are 3 possible toxic side effects of phenylephrine?
1. Hypertension 2. Pulmonary oedema 3. Arrhythmia
76
What are 2 groups of people that **10%** phenylephrine drops should never be used in and why?
1. Infants → high risk of pronounced side effects e.g. hypertension, bradycardia, reduced sats 2. Patients on systemic MAO inhibitors → effect can be potentiated
77
How do anti-muscarinic dilating eyedrops work?
Dilate the pupil by **paralysing ciliary muscle** (prevents constriction of **iris sphincter muscle** and **ciliary body**) → tonic sympathetic dilation acts unopposed
78
How do different anti-muscarinic dilating eyedrops vary? 2 ways
in potency and duration of action
79
What is the most commonly used anti-muscarinic dilating eyedrop?
Tropicamide
80
What are 3 examples of anti-muscarinic dilating eyedrops?
1. Tropicamide 2. Cyclopentolate 3. Atropine
81
What is tropicamide useful for?
Fundus examination
82
How long does tropicamide last for?
Short duration: around 6 hours
83
What is a potential disadvantage of tropicamide as an anti-muscarinic dilating eyedrop?
Less cycloplegia (paralysis of the ciliary muscle)
84
How does the onset & duration of cyclopentolate and atropine compare to tropicamide?
Act more slowly than tropicamide, but last long: 8-10 hours (rather than 6)
85
What are cyclopentolate and atropine preferably used for and why? (over tropicamide)
Preferable for producing **cycloplegia** for refraction in **children** i.e. acuity tests**,** as they often subconsciously accommodate in procedure, producing false results and these drugs are more cycloplegic
86
How do cyclopentolate and atropine work to prevent subconscious accommodation during refraction?
_Prevent *constriction*_ of **ciliary body** and hence _prevent focusing of the lens_
87
What should be suspected in any patient following intravitreal injections with decreased vision and a red, painful eye?
Endophthalmitis

Duke Elder: Finals Ophthalmology (Alice) (20 decks)

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