OptoP: Lubricants - Week 11 Flashcards
From external to internal, name the layers of the tear film
Lipid layer (0.1 um) Aqueous layer (8um) Mucin layer (0.8um)
Which layer of the tear film is the largest?
aqueous layer
Is the tear film in front of or behind the cornea?
in front of, obviously
What is Dry Eye Disease?
A multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms
What factors play key aetiological roles in DED? (4)
tear film instability
hyperosmolarity
ocular surface inflammation + damage
neurosensory abnormalities
What is tear osmolarity? (5)
In tears, it specifically refers to the concentration of small proteins and electrolytes (including sodium, potassium, and chloride)
Does osmolarity reveal the exact chemical composition of the tears?
No
What does tear osmolarity quantify?
How concentrated the tears are
How does tear film osmolarity differ in patients with DED?
Higher (over 308mOSM/L)
How does hyperosmolarity of the tears affect the immune system? (4)
Hyperosmolarity causes significant corneal epithelial stress that can result in increased levels of inflammatory mediators incl. pro-inflammatory cytokines and chemokines
Explain the technique for collecting tears [tearlab collection guide] (3 steps)
- Patient preparation: head back, eyes up, do NOT pull eyelid away
- Sample collection: px open eyes, bottom tip of pen contact lower eyelid and line of moisture
- Collection technique: move tip beyond eyelashes near corner of eye, avoid touching sclera, press down lightly on eyelid to collect tears, fluid is collected at bottom tip of test card
What proportion of the population have DED?
approx 15%
In regard to DED:
- How is incidence related to age?
- which gender has higher incidence?
- name 2 factors that contribute to DED
increases with age
females>males (2:1)
systemic medications, environment
What are the 2 types of DED?
ADDE: Aqueous deficient dry eye
EDE: Evaporative dry eye (lipid-deficient)
Can you have varying levels of both ADDE and EDE at the same time?
Yes
What 2 broad therapy types exist for DED?
Pallative therapy: relieve symptoms, doesn’t treat underlying pathology
Therapeutic treatment: targets the pathology/inflammatory process
What is the first line therapy for DED? For what levels of DED is it used?
Artificial tears/lubricating eye drops. Used for all levels of DED. For more severe DED, artificial tears are used in conjunction with other treatment, and we keep adding on other treatments on top of the artificial tears
What is the aim of ocular lubricants?
aim to replenish the patient’s (deficient) tear film with an exogenous volume enhancer
Can ocular lubricants differ in their mechanism of action?
yes
Are ocular lubricant formulations preserved or non-preserved?
can be either
What is the advantage of gels over other ocular lubricants? (1)
Longer retention time
Name 3 forms that ocular lubricants can be given in
drops
gels
ointments
What do eye lubricating ointments generally contain?
Paraffin
What is the typical standard dosing for ocular lubricants?
qid (4 times/day)
What is the clinical effect of ocular lubricants? (5)
Not entirely known; possibly one or more of:
Direct lubrication
Replacement of absent tear constituents
Improve tear spreading across ocular surface
Reduction in tear hyperosmolarity
Dilution/clearing of inflammatory cytokines
Describe the osmotic pressure of ocular lubricants in comparison to the eye (2)
Are either hypotonic (lower) or Isotonic (same)
What do ocular lubricants contain? (4)
Electrolytes
Surfactants
Viscosity-enhancing agents
possibly preservative but not always
WHY DO PLANTS LOVE OCULAR LUBRICANTS? lol
Because they have electrolytes, it’s what plants crave XD
What kind of electrolytes do ocular lubricants contain? Provide 3 examples
Sodium chloride
Potassium chloride
Calcium chloride
look at all that chloride! so many chlorides!
Imagine this scenario: Jimmy Neutron dropped his ocular lubricant on the floor. He’s asked what does it contain. What is the one electrolyte he mentions first?
Sodium chloride
then Skeet goes: I think you mean SALT
What do most ocular lubricant products target for therapy?
replenishing the tear aqueous layer
Are there any ocular lubricant products that act to supplement the lipid layer?
Yes. Some newer ones do that.
What kind of ocular lubricants are typically required for more advanced DED? But what is the issue with these?
More viscous solutions. But beware of effects on vision (blur)
If highly viscous ocular lubricants were a band, which one would they be?
Blur. Because they cause blur. Get it? haha
Describe the electrolyte composition of eye drops
Mimics the electrolyte composition of human tears
What electrolytes are most critical for ocular lubricants?
Potassium and bicarbonate. WHAT! NOT SALT?!?!? JIMMY NEUTRON WOULD BE ASHAMED!
Why is potassium an important component for ocular lubricants?
potassium is important for maintaining corneal thickness
Why is bicarbonate an important component for ocular lubricants?
bicarbonate promotes recovery of epithelial barrier function in damaged corneal epithelium; may also assist in maintaining the mucin layer of the tear film
What is the function of osmo-protective formulations of ocular lubcricants? (2) And what do they contain? (3 things in brackets)
Protect against the adverse effects of increased osmolarity (contain glycerin, erythritol, levocarnitine)
These solutes distribute between the tears and intra-cellular fluids to protect against cellular damage from hyperosmolar tears
What does tear stability depend on?
the chemical-physical characteristics of the tear film interacting with the corneal epithelium
What is the benefit of adding macromolecular complexes onto ocular lubricants?
act as viscosity-enhancing agents and/or wetting agents
If you have a really severe case of DED, what might you want to add onto your ocular lubricant and why?
Macromolecular complexes, to make the ocular lubricant more viscous
How do viscosity-enhancing and wetting agents help protect the ocular surface? (2)
by prolonging the retention of the drop in the eye
May also help restore the protective effect of the natural mucin layer
Name 5 examples of viscosity-enhancing and wetting agents
Cellulose ethers (e.g. CMC) Polyvinyl alcohol (PVA) Polyethylene glycol (PEG) Propylene glycol (PG) Sodium hyaluronate
What is the normal osmolarity of the tears in a healthy patient?
308
Why use a hyposmotic solution as an ocular lubricant?
To try and negate the hyperosmolarity of the tears in DED
In regard to Cellulose Ethers:
A: How viscous and elastic are they?
B: How do they affect the viscosity of the tears?
C: How do they effect the surface epithelium?
D: Name 2 side effects
A: They are visco-elastic polysaccharides, so they exhibit both viscous and elastic characteristics
B: Increase viscosity of the tears
C: “coat and protect” by binding to corneal epithelial cells
D: May cause lid crusting. Often transient blurred vision on installation
In regard to Polyvinyl Alcohol (PVA): A: What is it? B: How viscous is it? C: How water soluble is it? D: Does it cause blur?
A: synthetic monomers that act as wetting agents
B: low viscosity
C: good water solubility
D: does NOT cause blur
What is HP-guar and what is it used for?
Acts as a gelling agent in solutions containing glycol 400 and propylene glycol (systane) to promote a mucin-like layer on the surface when it hits the tear film
Describe the molecular mechanism of what HP-guar does, and the outcome of this (2)
Forms reversible cross-links with tetravalent borate ions at a pH above 7
Results in increased viscosity of the drop when mixing with tears (pH ~7.5)
What does HP-guar bind?
Preferentially binds to more hydrophobic/dessicated areas of the epithelium, providing temporary protection to those cells
Is HP-guar “muco-mimetic”? What does this term mean?
Yes. It means that it assists in aqueous retention at the ocular surface
In regard to Sodium Hyaluronate:
A: What does it contain?
B: How does its residence time compare to 0.3% HPMC and 1.4% PVA
C: Describe its effect (3)
A: Hyaluronic acid, which is a glycosaminoglycan
B: Longer residence time
C: Increases pre-corneal tear film stability and corneal wettability. Also facilitates wound healing
Describe the viscoelasticity of Sodium Hyaluronate
High
What is the aim of lipid-based products? (4)
To treat the ‘evaporative’ component of dry eye by replacing deficient lipid components of the natural tear film (induced by meibomian gland dysfunction, MGD) to improve tear stability
How can we observe the integrity of the meibomian glands to assess for MGD?
Evert eyelid and observe under infrared light. If we don’t see any gland, then that is Meibomian gland dropout
Describe the mode of action of lipid-based ocular lubricants (2)
Improve lipid layer thickness
Increase tear stability (TBUT)
How are lipid-based ocular lubricants typically used?
In combination with traditional therapies for managing MGD
What traditional therapies are used to treat MGD? (3)
Warm compress/lid massage
Omega-3 supplements
Oral doxycycline/topical corticosteroids (if severe)
Name 1 advantage and 1 disadvantage of preservatives in ocular lubricants
Adv: increased shelf life
Disadv: can cause ocular surface toxicity
Name 2 disadvantages of non-preserved ocular lubricants
Increased cost
Risk of microbial contamination (when patients re-use single-use vials)
What is the normal tear film pH?
6.9-7.5 (this is similar in both healthy and DED patients)
What factors influence the pH of eye drops? (2)
differences in carbon dioxide saturation
differences in meibomian lipids in tear film
What happens when the pH of the eye drop does not match the pH of the eye?
stinging sensation
What is the most common reason patients stop wearing contacts?
dry eye
How can we relieve dry eye in people with CLs?
CL rewetting drops: act to replenish the pre-lens tear film
What happens to your eye when wearing CLs for an extended period of time? e.g. overnight
Protein build up (note: protein cleaner “Blink’n’Clear”, and others, can fix this)
What is the purpose of CL solution? (3)
Disinfect CLs
Prevent/minimise lens deposits
Maintain CL hydration and wettability (for better comfort and vision)
What are the key requirements of a CL solution? (6)
antimicrobial efficacy (broad spectrum) be non-toxic to ocular tissues minimum effect on lens parameters be simple be convenient be inexpensive
What types of CL solutions are there?
Multi-purpose solutions (for softs and RGPs)
Hydrogen peroxide solutions (for softs and RGPs)
Daily cleaners
Rinsing solutions
Disinfecting solutions
Protein removers (enzymatic cleaner)
Name the possible components of CL solutions (7)
Water
Osmolarity adjusting agents/electrolytes (e.g. NaCl, KCl)
Buffering agents (e.g. boric acid, sodium borate)
Surfactants (e.g. tyloxapol, PEG-11)
Chelating agents (e.g. EDTA)
Viscosity-enhancing agents (e.g. HPMC)
Wetting agents (e.g. PVA, PVP)
What is the advantage of abrasive surfactants and detergents over non-abrasive. What is the disadvantage?
Adv: can remove more deposits, particularly ones that are really stuck in there, via mechanical removal
Disadv: can scratch the lens
Describe the features of Daily Cleaners? (2) What do they remove? (3) What are they primarily used for? (1)
Surfactant cleaners with broad efficacy
- they act to remove lipids, proteins, mucus
- primarily used for RGPs
Define disenfection
the process of reducing the number of potentially pathogenic micro-organisms on the CL to ‘safe’ levels
What are the 2 primary methods of CL disinfeciton?
Chemical
Hydrogen-peroxide
Name 4 common chemical disinfectants
Benzalkonium chloride (BAK) - eye drops
Chlorhexadine digluconate (CHX) - RGP solutions only
Biguanides - soft contacts and RGPs
Quaternary ammonium compounds - soft contacts and RGP solutions
In regard to BAK:
A: What is it effective against? (2)
B: What can you do to enhance its efficacy?
C: What does it bind to? What can this cause?
A: bacteria and fungi
B: combine it with EDTA
C: binds to hydrogel materials - cause toxicity reactions
In regard to CHX:
A: What is it effective against?
B: What does it have limited efficacy against? (3)
C: What does it bind to? What is the outcome of this?
A: Broad spectrum anti-microbial
B: Limited efficacy against S. marcesans, yeast, and fungi
C: Binds negatively charged bacterial cell walls/surfaces and can therefore disrupt membrane integrity, causing cell death
Is CHX a biguanide?
Yes. It is a cationic polybiguanide
How readily does CHX bind to mucus? What does this cause?
Readily binds to mucus, so you can’t use this as a cleaner unless you’ve already removed the mucus so the mucus won’t get in the way
Name 2 cationic antiseptics: What class of drug do these 2 drugs fall under?
“PAPB”/”DYMED” (polyaminopropyl biguanide)
“PHMB” or “Polyhexamide” (polyhexamide biguanide)
Both are biguanides
What is the most common preservative used in ocular lubricants?
Biguanides
Name 3 preservatives used in ocular lubricants (3)
BAK
CHX
Biguanides
Polyquad (don’t worry about this one)
How do Biguanides help preserve ocular lubricants?
They bind to bacterial DNA and alter transcription, thereby stopping replication
(also has some activity towards inhibiting bacterial respiratory enzymes)
Is Hydrogen peroxide a reducing agent or oxidising agent?
oxidising agent
List 2 advantages of using Hydrogen Peroxide in ocular lubricants
Preservative Free
Broad anti-microbial activity
List 4 disadvantages of using Hydrogen Peroxide in ocular lubricants
Residual peroxide may cause discomfort
Essentially no ongoing disinfection activity after neutralisation
Expensive
May be more difficult
What do protein cleaning solutions contain? (3)
proteases, lipases, mylases
What do lipases break down?
mucin
Can protein cleaning be given as a tablet?
Yes. A table dissolved in MPS or H2O2 to be precise
What is the effect of enzymatic/protein cleaning?
Removes bound insoluble protein
