Transcript Contact Lens Care Products: Properties and Performance

Contact Lens Care Products:
Properties & Performance
Lecture 5L3
Version:
2012-May-10
•
Published in Australia by
The International Association of Contact Lens Educators
SecondEdition 2011
1
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Published in Australia by
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Revised Edition 2011
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CONTRIBUTORS
Contact Lens Care Products:
Properties & Performance
Lakshman Subbaraman, PhD, BSOptom, MSc, FAAO
Lewis Williams AQIT(Optom), MOptom, PhD
For a complete list of acknowledgements please see our website:
www.iacle.org
CARE & MAINTENANCE
PURPOSES
• Clean CLs
• Prevent/minimize CL deposits
• Maintain CL hydration & wettability to 
 comfort &  vision
• Disinfect CLs to prevent ocular infection & inflammation
COMPLICATIONS
DEPOSITS
•   irritation &  comfort
•  visual acuity
•  CL life
•  bacterial binding   potential for infection
•  incidence of CLPC/GPC
COMPLIANCE
vs. NON-COMPLIANCE
• Simple system & appropriate instructions 
better compliance
• Complicated systems can lead to:
- confusion
- non-compliance
- complications  lens wear
COMPLIANCE INDEX
Collins & Carney (1986)
100
COMPLIANCE [%]
Good lens care compliance
80
Poor lens care compliance
60
50
50
40
40
20
20
10
0
Epithelial
Staining
5
Lens Deposits
Symptoms
CLINICAL ASPECTS
CARE & MAINTENANCE
PROCESSES
• Cleaning
• Rinsing
ESSENTIAL STEPS
• Disinfection
• Periodic protein removal
• Re-wetting/lubricating
• Care & replacement of CL case
ADDITIONAL
STEPS
LENS SPOILAGE
CL CARE PRODUCTS
CLEANERS
Formulation (main solution components):
• A strong surfactant
• A component to  solution’s viscosity
–  ‘stay time’ of cleaner
–  lubricity of cleaner on CL
• A solution preservative
– some solutions are self-preserving (e.g. contain alcohol)
• Water (the bulk)
CLICK FOR MORE
DETAILS ON VISCOSITY
CL CARE PRODUCTS
CLEANERS
Formulation (possible excipient components):
• Alcohol to  lipid solubility in water
• EDTA (EthyleneDiamine Tetraacetic Acid), a calcium (Ca++) chelating
agent that also  the mode(s) of action of many common preservatives
• A buffer system to control pH
• Agent(s) that ↕ osmolality
• A mild abrasive (fine, insoluble polymer  loosens or removes
adherent contaminants without altering CL surfaces)
Phillips & Czigler, 1985
CLICK FOR MORE
ON ALCOHOLS
CLICK FOR MORE
DETAILS ON BUFFERS/pH
CLICK FOR MORE
DETAILS ON OSMOLALITY
CL CARE PRODUCTS
CLEANERS
Formulation (preservatives): Older
Common preservative in earlier GP & PMMA LCPs were/are:
• Benzalkonium chloride (BAK), a quaternary ammonium compound
– BAK is still used in some older LCPs
• Thimerosal (also thimersal), a mercury-based (Hg) preservative
– regulatory & environmental authorities regard mercury (Hg)
compounds as environmental pollutants
CLICK FOR MORE DETAILS ON BAK
CL CARE PRODUCTS
CLEANERS
Formulation (preservatives):
• Preservative required if cleaner not self-preserving
– a biguanide. For SCLs, a polymeric biguanide, e.g. a polihexanide
(PHX, PAPB, PHMB), used - molecular size (8 nm)  ability to
penetrate lens matrix – usually with EDTA & borate buffer to 
antifungal efficacy
– a Quaternary Ammonium Compound. Currently, polymeric QAC
most common, e.g. polyquaternium-1 (PQ-1)
– sorbic acid has been used but uncommon now
– mercurials have been used but undesirable
CL CLEANERS
SURFACTANTS
• Surfactant (surface active agent): ‘wetting’ agent that 
surface tension (ST) of a liquid
– lowers the interfacial tension between two entities in contact, e.g.
LCP & CL
• Some organic compounds are amphiphilic (i.e. have
hydrophobic groups [tail] & hydrophilic groups [head])
– these compounds are soluble in both organic solvents as well as
water
CL CLEANERS
SURFACE TENSION (ST)
Surfactants disrupt surface
forces thereby lowering ST
CLICK FOR MORE
DETAILS ON ST
SURFACTANT CLEANERS
FUNCTIONS
• Remove deposits by:
– interacting with and/or modifying CL deposits
– displacing deposits from CL surface
• Emulsify oils & lipids
• Destroy/dislodge micro-organisms
• Prepare lens for rinsing & disinfection
• Increase the wettability of the CLs
SURFACTANTS IN LCPs
• Poloxamines (trade name: Tetronic)
– examples: Tetronic 1107 (ReNu MultiPlus), Tetronic 1304 (Alcon’s
OPTI-FREE products), & Tetronic 1307
• Poloxamers (trade names: Pluronic & Poloxamer)
– examples: Pluronic F87 (Poloxamer237), Pluronic F127 (Poloxamer
407), & Pluronic 17R4
• Isopropyl alcohol (CIBA Vision’s Miraflow)
• Tyloxapol (AMO’s Complete MoisturePlus)
• Cremophor RH 40 (a.k.a. Aqualube™, CIBA Vision’s Focus
Aqua™)
SURFACTANT CLEANERS
TYPES
• Daily cleaners
• Periodic cleaners
SURFACTANT CLEANERS
CURRENT MARKET
• Currently, few single-purpose CL cleaners available.
Probable reasons:
– dominance of disposable CLs
– increased market penetration of DD CLs
– dominance of MPSs & OBSs
– desire to rationalize number & type of LCPs made/stocked
– some products are only sold in the country of manufacture & remain
virtually unknown outside their own domestic market
CLICK FOR A LIST OF CURRENT CL CLEANERS
EXCIPIENTS
GENERAL
• Solution excipients play ‘supporting’ rôle. Such
rôles include:
– ↕ solution pH, tonicity, or viscosity
–  efficacy of main (active) components
COMMON EXCIPIENTS
LCPs FOR GP CLs
• Sodium chloride (sea salt)
• EDTA & derivatives
• HPMC (HydroxyPropylMethylCellulose)
• HydroxyEthyl Cellulose
• Sodium Na Phosphate (monobasic, dibasic)
• Sodium LauroAmphoDiAcetate, CocoAmphoDiAcetate
• Poloxamers
• PVA (PolyVinylAlcohol)
• Tyloxapol
• Alkyl Ether Sulphate
COMMON EXCIPIENTS
LCPs FOR Hy & SiHy CLs
• Sodium chloride
• EDTA & derivatives
• Boric acid, Na Borate (borate buffer system)
• Sodium Citrate, Citric acid (citrate buffer system)
• HPMC (HydroxyPropylMethylCellulose)
• Sodium Phosphate (monobasic, bibasic)
• Poloxamines
• Poloxamers
• PPG (ProPyleneGlycol)
• AminoMethylPropanol
• HydroxyAlkylPhosphonate
• NaOH (to  pH) & HCl (to  pH)
EXCIPIENTS
IDENTIFICATION
• Usually, solution excipients are itemized on bottle & outer
carton (if used)
• Additional data can be found in product’s MSDS (Material
Safety Data Sheet)
– MSDSs often  CAS Registry Numbers that identiy components
uniquely & unambiguously
• Not all manufacturers make MSDS readily accessible
CLICK FOR MORE ON CAS RNs
EXCIPIENTS
CHELATING AGENTS
• Components that act synergistically with others
to  disinfection efficacy,
OR
• Components that facilitate the removal of tear
film components, especially calcium
compounds or tear proteins
CHELATING AGENTS IN LCPs
EDTA (EthyleneDiamine Tetraacetic Acid)
– in a majority of MPSs
– cationic (–ve) chelating agent that binds free metals & 
disinfectant antimicrobial activity
– sequesters ions such as calcium (Ca++) & magnesium (Mg++)
that compete with +ve charged preservative molecules for active
sites on microbial cell walls. Consequently, micro-organisms
become more susceptible to preservative penetration
CLICK FOR MORE ON EDTAs
EDTA CHEMISTRY
CHELATING AGENTS IN LCPs
contd...
• Citrate
– in Alcon’s OPTI-FREE EXPRESS & OPTI-FREERepleniSH
– sequestering agent that  passive removal of tear proteins
• Hydroxyalkylphosphonate
– in B&L’s ReNu MultiPlus (trade name: Hydranate)
– sequestering agent, breaks the chemical bonds between the deposits
& CL, & between different protein elements themselves
– having multiple –ve charges, sequestering agents are attracted to +ve
charged tear proteins. They attach to tear proteins & separate them
from the CL through repulsive forces
500 mL SALINE STUDY
WIDE-MOUTHED BOTTLES
% CONTAMINATED
Sweeney et al., 1992
100
100
100
100
100
100
100
100
80
60
50
40
20
0
Week 1
Week 2
Week 3
WEEKS OF USE
Test
Control
Week 4
500 mL SALINE STUDY
JET or SMALL APERTURE BOTTLES
% CONTAMINATED
Sweeney et al., 1992
WEEKS OF USE
SALINE SOLUTIONS:
RECOMMENDATIONS
• Unit-dose, unpreserved best but $$
• Aerosol better than bulk, unpreserved
• If bulk saline used:
– select smaller volume bottles
– seek small-bore dispensing jets/nozzles
– replace solution ≤1- 2 weeks after opening
• it is better not to use such products
CLICK FOR MORE DETAILS ON EXPIRY, USE-BY, etc.
WHY IS DISINFECTION
REQUIRED?
CLs can:
• Inhibit tear film’s washing action
• Introduce micro-organisms
• Compromise the epithelium’s barrier function
DISINFECTION: FUNCTION
Disinfection is central to  number of
potentially harmful micro-organisms
on CLs
DISINFECTION: SYSTEMS
• Thermal (heat) (some trial CLs)
• Hydrogen peroxide (1-Step or 2-Step)
• Chemical
- conventional (largely historic)
- polymeric (currently mainstream)
- tablet (largely historic)
• Subsonic/ UV-C disinfection (uncommon)
DISINFECTION: THERMAL
• Earliest form of disinfection
• Still the most effective
• Originally high temperatures (90-100°C)
• Later, lower temperatures (70-85°C)   denaturation of
deposits
• Micro-organisms killed by:
– Denaturation of cell components
– Disruption of plasma membranes
– Damage to the organism’s DNA
No longer used by wearers
Still used on some trial CLs
THERMAL: ADVANTAGES
• Short disinfection times
• Highly effective
• Low risk of toxic or allergic reactions (until denatured tear
film components, e.g. lysozyme, bind to CL surfaces)
THERMAL: DISADVANTAGES
• Incompatible with many current CLs
• Electric power not always available
– boiling water in a vacuum flask a possibility
– boiling lens case in saucepan very risky
• Heat can  lens discolouration (mainly of deposition, not
lens material per se)
•  protein deposition
–  protein denaturation & bonding to CL material
DISINFECTION/PRESERVATIVES:
KNOWN OCULAR IRRITANTS
• Thimerosal (a Hg-based compound)
• Chlorhexidine (a biguanide)
• Sorbic Acid (now uncommon)
DISINFECTANT SENSITIVITY
SYMPTOMS
• Sudden  in ocular
tolerance
• Decreased wearing time
(2-4 hours)
• Burning, gritty, dry
sensation
SIGNS
• Conjunctival redness
(general/localized)
• Epithelial damage (diffuse
corneal staining)
• Corneal inflammation
(if severe)
DISINFECTANT SENSITIVITY:
INCIDENCE: 5-30%
Depends on:
• Disinfectant type (e.g. peroxide, biguanide, QAC, etc.)
• Specific preservative (e.g. CHX, PHX, PQ-1, etc.)
• Preservative concentration (3% to 0.0005%)
• Lens materials (e.g. PMMA, SA, FSA, Hy, SiHy, Hybrid)
• Soaking time (e.g. 1-8 hours)
• Lens age (e.g. days or months, ‘years’ should not arise!)
• Patient susceptibility (individually variable, other known
sensitivities?)
CHEMICAL DISINFECTANTS :
CONVENTIONAL
• Thimerosal
(historic only)
• Chlorhexidine (historic?)
• Sorbic Acid (historic)
• ATAC
(historic)(Alkyl TriethanolAmmonium Chloride)
• Isopropyl alcohol* (historic, now cleaner only)
EDTA is often used as an antimicrobial enhancer
CHEMICAL DISINFECTANTS :
POLYMERIC
The basis of all current MPSs
The polihexanides (PHX), a generic term for:
CLICK FOR MORE
ON PHXs
• Poly(aminopropyl biguanide) (PAPB)
• Poly(hexamethylene biguanide) (PHMB)
• Alexidine (not actually a polymeric disinfectant)
The poly(quarternary ammonium) compounds (polyquats):
•
Polyquaternium-1 (PQ-1)
CLICK FOR MORE
ON PQ-1
POLYMERIC DISINFECTANTS:
ADVANTAGES
• ‘Adequate’ for routine disinfection tasks
• Boost et al. (2010) showed that except for some fungal isolates,
MPSs performed adequately (99.9% viability reduction) on FDA testpanel organisms & some related clinical isolates
• Lend themselves to simplicity
• MPSs & OBSs became possible
• belief (hope?) is that simplicity  compliance
• combination of MPS & disposable CLs   marketability of CLs in
general (CL wear seems less complicated)
• Fewer adverse outcomes from their use cf. earlier
generations of disinfectants
• however, the rate is still not zero
POLYMERIC DISINFECTANTS:
DISADVANTAGES
• Reduced disinfecting ‘power’
• because eye is exposed to CL-borne disinfectant, efficacy a
compromise between antimicrobial & ocular toxicity
• Rub/rinse still required
• physical loosening & removal of ocular debris, including microorganisms,  task of disinfectant subsequently
• Compliance more important
•  margin for error due to  (deliberate) solution antimicrobial
efficacy
ANTIBACTERIAL EFFICACY*
MRDTs#
after Lowe et al., 1992, Reinhardt et al., 1990
•
Heat (80°C, 10 min)
•
3% H2O2 (2-Step) (10 min) (unneutralized)
•
3% H2O2 (1-Step) (6 hrs) (disc neutralization)
•
0.002% Thimerosal (4 hrs)
•
0.00005% PHMB (4 hrs)
•
0.001% PQ-1 (4 hrs)
* within MRDT
ANTIFUNGAL EFFICACY*
after Lowe et al., 1992, Reinhardt et al., 1990
POOR
GOOD
•
Heat (80°C, 10 min)
•
0.00005% PHMB (4 hrs)
•
3% H2O2 (2-Step) (10 min)
•
0.001% PQ-1 (4 hrs)
•
0.002% Thimerosal (4 hrs)
•
3% H2O2 (1-Step) (6 hrs)
* within MRDT
ANTIAMOEBIC EFFICACY*
after Davies et al., 1990
GOOD
POOR
•
Heat (80°C, 10 min)
•
0.00005% PHMB (4 hrs)
•
3% H2O2 (2-Step) (4 hrs)
•
0.001% PQ-1 (4 hrs)
•
0.002% Thimerosal (6 hrs)
•
3% H2O2 (1-Step) (6 hrs)
* within MRDT
POLIHEXANIDE (PHX)
• Originally from anti-malarial water treatment research in early
1960s. Subsequently used as a swimming-pool disinfectant,
cosmetics preservative, antifungal in water-based inks (for pens),
as an industrial disinfectant, & in antibacterial wipes
• Found in many MPSs from AMO, B&L, CIBA Vision, Sauflon and
many second-tier LCP manufacturers
• Other names:
– polyhexanide, polihexanide, polyhexidine
– PHMB, PAPB, alexidine (not polymeric)
– trade names: Dymed, TrisChem
POLIHEXANIDE (PHX)
Modes of action:
• PHX binds readily with exposed phospholipid groups of
outer plasma membrane of microbial cells
• PHX’s long-chain polymeric nature provides optimal
antimicrobial activity, allowing multiple sites along the
molecule to bind to microbial cell wall
• This creates a large bulky domain on the microbial
cytoplasmic membrane causing disruption and ultimately,
cell lysis
POLYQUATERNIUM–1 (PQ–1)
• Found in:
– Alcon’s OPTI-FREE products (trade name: Polyquad [derivation:
polyquaternary - polyquat])
– B&L’s Biotrue
– AMO Revitalens Ocutec
• PQ-1 is a high molecular weight biocide with a significantly
greater molecular size, i.e. > CHX & Thimerosal
• PQ-1’s large molecular size  penetration of Hy or SiHy lens
matrix
– this  PQ-1 accumulation within CLs
– little accumulation means  PQ-1 release from CLs &  ocular toxicity
• It is more effective at lower concentrations than CHX
MyristAmidoPropylDimethylAmine
(MAPD)
• Alternative name: Amidoamine
– trade name: Aldox
• Used in Alcon’s OPTI-FREE Express & OPTI-FREE
RepleniSH as a complementary biocide
• Has antifungal & antiamoebic properties
ALEXIDINE (ALEX)
• Alexidine, like CHX, is a non-polymeric, amphipathic, cationic
bisbiguanide antiseptic long used in mouthwashes
• Highly effective against bacteria & Acanthamoeba sp.
– is both bactericidal & bacteriostatic
• Alexidine has ethylhexyl end groups whereas CHX has parachlorophenyl radicals – their ‘backbones’ are identical (next slide)
• Alexidine is more rapidly bactericidal and produces a significantly
faster alteration of cells (by membrane disruption)
•
Can be inactivated by anionic compounds, organic matter, &
extremes of pH
ALEXIDINE (ALEX)
Ethyl group
Hexyl group para-Chlorophenyl group
Biguanide group
CLICK FOR CURRENT DISINFECTANTS/MPSs
HYDROGEN PEROXIDE (H2O2)
 free oxygen radicals that are very reactive &
bind quickly to many microbial cell components
2H2O2
2H2O + O2
Hydrogen peroxide solutions require a
stabilizer in the interests of long-term stability
CLICK FOR MORE
ON H2O2 & STABILIZERS
HYDROGEN PEROXIDE (H2O2)
A non-selective antimicrobial agent
Neutralization: 2-step systems
– serial dilution (historic, imperfect, [H2O2] ≠ 0 )
– pH shifting (historic, 1st generation, NaHCO3)
– reactive (stoichiometric) (historic, Na Pyruvate, Na Sulphite, or Sodium
Thiosulphate)
– catalytic (metallic [Pt] or catalase [biological])
Neutralization: 1-step systems
•
Catalytic disc (usually platinum-carbon)
•
Delayed-release catalase tablet (biological catalase)
– 20 min or 40 min (colour indicator may be included)
– slow start
– fragmentation aid included in tablet formulation
HYDROGEN PEROXIDE (H2O2)
2-Step Systems
Minimum 3 hours in 3% H2O2 recommended,
overnight preferred (6-9 hours)
• Bacteria
• Fungi
• Acanthamoeba sp.
10-15 min
60 min
3 - 6 hours
• Suitable for all lens types (including GP CLs)
HYDROGEN PEROXIDE (H2O2)
2-Step Systems: ADVANTAGES
• Can vary disinfection time
– unlimited possibilities, min. recommended 1 hour
• Concurrent protein removal possible
– peroxide-compatible product required
• Better suited to the occasional wearer
– lenses can be stored in unneutralized peroxide
– 3-monthly solution replacement recommended
HYDROGEN PEROXIDE (H2O2)
2-Step Systems: DISADVANTAGES
• Less convenient
– effort required to commence neutralization
– more component ‘parts’ (bottles)
• If preserved neutralizing solution used
– potential for irritation
– shorter Expiry: & Discard-After: dates (than peroxide)
• Can be more expensive
•
Perception that too much packaging used
HYDROGEN PEROXIDE (H2O2)
STOICHIOMETRIC NEUTRALIZATION
• Longer neutralization/equilibration times required
• Vented lens case not required
– simpler & less expensive
• No ‘activity’, e.g. bubbling, visible
– no visible confirmation of neutralization
HYDROGEN PEROXIDE (H2O2)
CATALYTIC NEUTRALIZATION
• Earliest: platinum(Pt) & carbon (C) coated disc
(American Optical Septicon system)
– not a 1-Step system in its original form
• Biological catalase
– biological sources
– later, microbiological sources
• Vented lens case required
• Visible ‘activity’, e.g. vigorous bubbling
– confirmation that system is working
HYDROGEN PEROXIDE (H2O2)
1-Step System: ADVANTAGES
• Convenient
• Preservative-free (disc or tablet neutralization)
• Concurrent protein removal possible
– peroxide-compatible product required
• such products are available off-the-shelf
HYDROGEN PEROXIDE (H2O2)
1-Step System: DISADVANTAGES
• No control over disinfection phase
• [H2O2]  rapidly (3 to 1% <10 min)
• Ineffective against some fungi and encysted Acanthamoeba
sp.
• Catalytic disc needs regular replacement
– paradoxically, infrequent change   disinfection efficacy
• Potential for irritation
– tablet system: tablet components
– disc system: catalyst ‘poisoning’   residual peroxide
• Possible re-contamination (unpreserved resulting solution)
HYDROGEN PEROXIDE (H2O2)
[H2O2] & pH
changes
during a
peroxide
DISINFECTION
cycle
HYDROGEN PEROXIDE (H2O2)
Advice on 1-Step peroxide system usage
• Place CLs in their respective baskets
• Holding case vertically, fill case with peroxide to fill-line
• Insert lid/baskets into solution quickly (disc systems) and
screw lid down firmly
• Holding case vertically, shake case  &  several times to
bathe the lid and case walls in peroxide
or...
• Add tablet to solution and then insert lid/baskets without delay
(catalase system) and screw lid down firmly
• Shake as above
HYDROGEN PEROXIDE (H2O2)
Effect of peroxide on CLs (more relevant to 2-Step
systems)
• May cause reversible lens parameter changes in higher water
content CLs
• Changes take a little time to reverse (equilibrate) once
peroxide concentration is reduced or neutralizing solution is
introduced
– the higher the water content, the longer it takes to reverse
induced parameter changes
HYDROGEN PEROXIDE (H2O2)
Caution required
Chalmers et al., 1989
• Unneutralized or incompletely neutralized peroxide in CLs
will result in discomfort/pain/ocular irritation on insertion
(see next slide for thresholds)
– anterior eye has 3 peroxidative enzyme ‘systems’ for dealing with
hydrogen peroxide exposure
•
Located in:
Can deal with:
glutathione peroxidase (corneal epithelium [medium concentrations])
•
superoxide dismutase (corneal epithelium [medium concentrations])
•
catalase:
–
(conjunctival epithelium [heavy concentrations])
–
(corneal epithelium [medium concentrations])
HYDROGEN PEROXIDE (H2O2)
OCULAR TOLERANCE
Chalmers & McNally, 1988, Janoff, 1990, McNally, 1990
Anterior eye ‘detection’ (discomfort) thresholds for H2O2
•
If a solution contains H2O2 (a pulse-dose), 812 ppm (SD ±312) will be detected
with 95% probability
•
If a 55% water hydrogel CL has residual H2O2 (a sustained-release dose), 267
(SD ±69) ppm will be detected (95% probability)
•
If a 38% water hydrogel CL is used 282 (SD ±62) ppm will be detected (95%
probability)
•
Values are also subject to individual variation (McNally, 1990)
•
Furthermore, ‘symptoms’ experienced may not be due to [H2O2] but to soaking
solution/lens pH (too low) (Janoff, 1990)
CLICK FOR A LIST OF CURRENT PEROXIDE SYSTEMS
LESS CONVENTIONAL
DISINFECTION METHODS
CLICK FOR MORE
ON ClO2
• Sodium chlorite  Chlorine dioxide
• UV-C irradiation (induces DNA cross-linking in microorganisms or cells causing death)
– can be combined with subsonic or ultrasonic agitation as a cleaning aid
• Combined ultrasonic & low heat (<80°C)
– some thermal disinfection and some cleaning effect
– did not prove popular, safety?
• Microwave oven
– high heat  denaturation of biological lens contaminants
– vented case essential if ‘explosion’ is to be prevented
– highly effective (a variation of thermal disinfection in reality)
TRIAL SET DISINFECTION
• Trial lens set should be disinfected at least monthly
• Thermal disinfection is safest
– not all CLs can be disinfected thermally
• If using chemical disinfection, vials & CLs should be cleaned
periodically & solution changed regularly (every 2 weeks?)
• Use disposable (single-use) trial CLs if possible
– majority of CLs now disposable so a  issue
– however, not all CLs likely to be disposable in the foreseeable future
(Callender et al., 1992)
TRIAL SET DISINFECTION
RECOMMENDATIONS
• Use thermal disinfection for low water content
• Clean lenses with alcohol-based
cleaner prior to storage
– alcohol cleaner availability?
• Use unneutralized peroxide on
high water lenses
– must anticipate usage to adequate neutralization
• Use disposable lenses if possible
PROTEIN REMOVAL
• Effective protein deposit removal is essential in all CLs except
very frequent disposables (<14 – <30 days – patientdependent)
• Generally, only protein deposits are removed
– little or no effect on other deposits
• Function by breaking disulphide bonds in protein structure
(next slide)
– divided protein more readily removed or dislodged
CONTACT LENS CARE
PROTEIN REMOVAL
To remove a protein,
it must be hydrolyzed
For lysozyme, the
four S–S (disulphide)
bonds must be
cleaved (broken) to
allow an ‘unraveling’
of the protein chain
5L1-73
PROTEIN REMOVAL
• Done regularly, after daily cleaning & rinsing steps
• Can be done BEFORE disinfection, or done DURING
disinfection (with H2O2 systems, compatible enzyme
required)
• BEFORE: Lenses soaked in MPS or saline with enzyme
dissolved in solution - 15 min to overnight (depends on
manufacturer’s recommendation)
• CLs should be rubbed & rinsed thoroughly in MPS or sterile
saline after protein treatment (enzymes are biological entities)
• Protein removal must be followed by disinfection
PROTEIN REMOVAL
• DURING: Protein remover tablet placed in peroxide after
case is filled but before the CLs immersed or neutralizing
tablet added
• Processing time is governed by the peroxide system’s
disinfection recommendations
• Lenses should be rubbed and rinsed thoroughly with fresh
sterile saline after protein treatment immediately before
lens insertion (enzymes are biological entities)
PROTEIN REMOVERS
Soft CL protein removers usually contain one of the following:
• Papain
• Pancreatin
• Subtilisin A or Subtilisin B
GP protein removers are not necessarily enzymatic,
e.g. Progent (Menicon):
– Dose A contains sodium hypochlorite (NaClO, a bleach)
– Dose B contains potassium bromide (KBr)
PROTEIN REMOVERS
Papain
•
Protease from papaya (paw paw) plant
•
Binds to CL materials, can cause sensitivity reactions
•
Short 15 minute soaking time possible
Pancreatin
•
Protease (targets proteins), lipase (targets lipid), & amylase (targets polysaccharides)
•
Porcine pancreas derivative (religious & vegan concerns?)
•
Cleaning efficacy similar to papain
Subtilisin A & B
•
Proteases, derived from Bacillus sp. bacteria
•
Low toxicity, used in food products
•
Less specific binding characteristics
•
May be more effective than papain
CLICK FOR A LIST OF CURRENT PROTEIN REMOVERS
RE-WETTING & LUBRICATING
DROPS
Used for:
• Alleviating symptoms of:
– dryness, esp. ‘end of day’ sensations of dryness, a common SCL wearer
complaint
– discomfort
– ‘tiredness’
• Flushing contaminating and/or irritating particles from
eyes & CLs
• Cleaning CLs in situ
• Rehydrating lenses in situ
RE-WETTING & LUBRICATING
DROPS
Considerations:
(after Tonge et al., 2001)
• Short ‘stay’ (residency) time
• Must operate within narrow tear pH range
• Cornea’s permeability to most entities is low
• High & fast loss from the anterior eye (tear drainage)
–  solution viscosity is one strategy to  loss
– alternatively, incorporate a mucoadhesive polymer
• PVA & hyaluronic acid (HA) have mucoadhesive properties
• Must have low toxicity (compatible preservative or unpreserved)
• Must not: destabilize tear film,  TBUTs,  dry eye
RE-WETTING & LUBRICATING
DROPS
Useful for:
• Marginal dry eye patients
• Dry or air-conditioned environments
• Windy conditions (eye protection still advisable)
• Tired eyes
• Alleviating allergy symptoms
– is allergen known and/or avoidable?
– does allergy per se need treatment?
• If re-wetting drops needed often, continue CLs?
CLICK FOR A LIST OF CURRENT REWETTING PRODUCTS
DEMULCENTS
• Relatively new class of solution component in some
modern LCPs
• Usually, demulcent is a water-soluble polymer applied to
the eye topically to:
– protect & lubricate mucous membranes (e.g. conjunctiva)
–  dryness symptoms &  irritation
• Demulcents help to  comfort by modifying CL surfaces
DEMULCENTS
• HydroxyPropylMethylCellulose (HPMC) used in dry eye products,
tablet coatings, drug release systems (& 1-Step peroxide neutralizing
tablets), & to  solution viscosity
– HPMC effective in controlling symptoms & signs of dry eye
• Propylene glycol (PPG) used as moisturizer in medicines, cosmetics,
foods, & as medical lubricant , as a humectant food additive (E1520),
in hand sanitizers, antibacterial lotions, & saline solutions
• Used in Alcon’s OPTI-FREE RepleniSH as an agent to enhance
water retention on the surface of SCLs/SiHy CLs
DEMULCENTS IN LCPs
Dexpanthenol (Dexpant-5)
• Used to  lens wetting & lubricity
• Used in some dry eye products
Sorbitol
• Enhances CL wettability
– also used to adjust solution osmolality
RÔLE OF
RUBBING & RINSING
•  popularity of SiHy CLs has seen an  in practitioners
recommending CL rub & rinse
• Rub & rinse important (Franklin, 1997) because:
– SiHy CLs deposit lipid and/or other tear components on & in lens
matrix. This deposition can only be removed effectively by rubbing
(Nichols, 2006, Ghormley & Jones, 2006)
– frequently, wearers report  comfort if they rub their CLs
– rubbing & rinsing alone removes >90% of micro-organisms from a
lens
OCCASIONAL & INFREQUENT
WEARERS
Storage
• CLs should be stored in disinfecting solution
The following are UNSUITABLE for long-term storage:
• MPSs, (low concentration of preservative)
• 1-step peroxides (peroxide concentration decreases
rapidly, no preservation remains after neutralization)
OCCASIONAL & INFREQUENT
WEARERS
• Before use, clean & disinfect CLs again
– surfactant cleaner a must
• Select an appropriate disinfection system
• Replace the storage solution at least every 2 weeks while
lenses remain idle (more often has merit)
• Use preserved saline for rinsing (a sensitivity is less likely if
only used fleetingly for rinsing)
• Protein removal as needed
– a preventative approach advisable
OCCASIONAL & INFREQUENT
WEARERS: THERMAL DISINFECTION
• Low water content CLs only
• Lens storage case to remain airtight & sealed during & after
disinfection
– case must NOT be opened after disinfection
• Clean thoroughly before disinfection using a surfactant
cleaner
• Clean & disinfect again just prior to next use
• Infrequent disinfection means little deposition
• Lens life/replacement rate difficult to determine
OCCASIONAL & INFREQUENT
WEARERS: 1-STEP PEROXIDE USERS
• Disinfection & neutralization period & neutralization method is
product-dependent
• To maintain peroxide concentration at 3%:
– platinum disc system: disc must be removed first
– tablet neutralizer: tablet must not be used
• Vented case required for all systems
– allows liberated oxygen to escape (natural, slow decomposition)
• high-pressure relief valve, or...
• gas-permeable filter (sub-micron pore size, micro-organisms & other
contaminants denied access to lens case)
OCCASIONAL & INFREQUENT
WEARERS: 1-STEP PEROXIDE USERS
• Change peroxide every 3 to 6 months even if case remains
unopened between changes
• Neutralize lenses before wear using system’s normal
method
– need to anticipate need for lens neutralization
– need to factor in the normal neutralization time
• most systems need at least 1 hour, 2 hours preferred
• do not mix & match lens care systems
CLICK FOR MORE DETAILS ON SOLUTION
INCOMPATIBILITIES
OCCASIONAL & INFREQUENT
WEARERS: 2-STEP PEROXIDE USERS
• Store CLs in unneutralized 3% peroxide
• Change peroxide every 3 to 6 months even if case remains
unopened between changes
• Neutralize before lens wear using system’s normal method
– unpreserved neutralizer preferred
– need to anticipate need for lens neutralization
– need to factor in the normal neutralization time
• most systems need at least 1 hour, 2 hours preferred
LENS STORAGE CASE CARE
Replacement cases
LENS STORAGE CASE CARE
• Scrub weekly with a new, clean toothbrush (hard/firm rather
than soft) & CL CLEANING solution
• Rinse with sterile saline or MPS & shake excess solution
from case
• Air dry upside-down
• Replace regularly (at least 3 monthly)
Recently, antibacterial lens cases have been marketed
• Case polymer is impregnated with silver ions (Ag+) that
reduce bacterial contamination & biofilm formation
CARE & MAINTENANCE:
SUMMARY
• Do not mix solution types, technologies, or brands unless
you have a deep understanding of the underlying science
(see INCOMPATIBILITIES in the Appendix)
• Review patient compliance at every opportunity
• Ask patient to repeat instruction & demonstrate technique &
procedure
• Observe recommended storage conditions
CARE & MAINTENANCE:
SUMMARY
C lean
R inse
A nd
D isinfect
L enses
E very time
OR.....
CARE & MAINTENANCE:
SUMMARY continued...
If in doubt, throw them out!
IACLE INDUSTRY SPONSORS
5L1-97
APPENDIX
START
• The information in the following pages is included for
completeness
• It supports the information included in the body of
this lecture by providing a more in-depth treatment
of the topics covered
• If even greater depth is required, specialized text,
the web, or subject experts should be consulted
• These sections are also hyperlinked in the text
where appropriate
SOLUTION CHARACTERISTICS
BUFFER SYSTEMS
• Buffers: solution component ‘systems’ that help resist solution pH
changes, i.e. when an acid or a base is added to the solution - overall
solution pH changes little or not at all
– usually, buffer systems are combination of weak acid or weak base &
one of its salts, e.g. boric acid & sodium borate
• The 4 common buffer systems are:
– bicarbonate (unstable thermally)
– phosphate (can precipitate calcium phosphate  white spots & lens
calculi)
– borate (used in LCPs)
– citrate (used in LCPs)
– It has been suggested that synergies exist between particular buffers
& antimicrobials, e.g. borate buffers & PHX (Lever and Miller, 1999), &
citrate buffers & PQ-1 (Franklin, 1997; Hong et al., 1994)
SOLUTION CHARACTERISTICS
pH
•
•
•
•
Solution pH is the negative log (base 10) of its hydrogen ion concentration
– i.e. pH = – log [H+]
Solution pH:
– affects biocidal performance (see Parker, 1988)
– affects lens parameters (& fitting behaviour) by altering water content ( pH 
 lens water content)
– can affect a LCP’s ability to remove protein, especially from group IV CLs
– in –ve charged SCLs, pH can affect hydrogel expansion, facilitating release of
soluble proteins into storage medium (Tonge et al., 2001)
López-Alemany et al. (1997) showed significant variations in MPS pH over time
(values ranging from 6.84 to 7.63, they concluded that pHs within buffer capacity
of the anterior eye)
Lau & Jones (1999) reported solution pHs ranging from 5.95 (AOSept® before
neutralization, 6.14 after) to 7.72 (OPTI-FREE® EXPRESS®). UltraCare® (a 1step + tablet neutralizer peroxide system) solution pH before: 3.51, after: 6.7
(expected because neutralizer tablet ‘restores’ pH to physiological levels – low
peroxide pH improves solution stability)
SOLUTION PROPERTIES
ACIDS & BASES
• ACID:
– Brønsted-Lowry (1923) definition: PROTON donor
– Lewis (1923) definition: ELECTRON PAIR acceptor
The Lewis definition is applicable more generally
• BASE:
– Brønsted-Lowry (1923) definition: PROTON acceptor
– Lewis (1923) definition: ELECTRON PAIR donor
• On the pH scale:
– pH < 7 is ACIDIC
– pH 7.00 is NEUTRAL (e.g. pure water @ 25°C)
– pH >7 is BASIC
RETURN TO LECTURE
SOLUTION PROPERTIES
VISCOSITY
•
•
•
•
Viscosity: fluid’s (i.e. liquid or gas) resistance to flow or pouring
– technically, resistance to deformation in shear. Due to intermolecular friction
& molecular adhesion & cohesion within the fluid
– the terms ‘thick’ (high viscosity) & ‘thin’ (low viscosity) used frequently as
qualitative descriptions of liquid’s viscosity
– viscosity also temperature dependent ( temperatures   viscosity)
SI unit of viscosity: Pascal second (Pa.s) but for practical liquids, milliPascal
second (mPa.s = 0.001 Pa.s) used. Poise in another metric unit although
customarily, the centipoise (cP= 0.01 poise) is used. 1 Centipoise = 1 milliPascal
second (viscosity of pure water: 1 mPa.s at 20°C)
Often, solution viscosity  to   ‘stay-time’ (residency) (LCPs/in-eye products)
– to many consumers:  viscosity =  ‘effectiveness’
– sometimes viscosity  to  solution demulcent properties, i.e. soothing ,
irritation-reducing, slippery. Solution demulcents include PVP, PVA, &
polyethylene glycol (PEG)
Lau & Jones (1999) reported solution viscosities from 0.935 mPa.s (AOSept®
after neutralization) to 2.875 (COMPLETE®)
RETURN TO LECTURE
SOLUTION PROPERTIES
OSMOLALITY
•
•
•
•
Osmolality & osmolarity describe osmotic pressure of solution
– measures of the number of ions or molecules in solution
– the following applies to solutions, solutes, solvents, and separating
membranes behaving ideally, i.e. the solvent (usually water) can pass freely
through the membrane unlike the solute
Osmolality is the number of osmoles of solute per kilogram of solvent (mOsm/kg)
Osmolarity is the number of osmoles of solute per litre of solution (mOsm/L)
– osmolarity is more difficult to deal with computationally because solution
volume varies somewhat as solute is added. For dilute solutions, the
differences between osmolality and osmolarity are small and can be ignored.
Furthermore, 1 kg of water & 1 L of water used interchangeably. While a
reasonable approximation, it is not strictly correct because one litre of pure
water weighs 1 kg only at its maximum density (999.972 kg/m3 @ +3.984° C
at 1 atmosphere of pressure). This suggests that 1 L is not 1,000 cm3 but
1,000.028 cm3, i.e. 1 mL is fractionally smaller than 1 cm3.
Solution osmolality =  the osmotic pressures of each of the solutes present
SOLUTION PROPERTIES
TONICITY
•
•
•
•
•
•
Tonicity: qualitative, dimensionless description of whether steady-state volume of
a body cell changes when placed in the solution
Isotonic solution: one that does not alter the cell’s steady-state volume. The
osmotic pressure of blood plasma is equivalent to 0.9% NaCl or about 300
mOsm/kg (depending on measuring technique)
Isosmotic (iso-osmotic) solutions: solutions whose osmolalities are equal
– however, isosmotic  isotonic because some solutes can pass through
dividing membranes selectively (e.g. a cell’s membrane), i.e. membrane is
said to be semipermeable. In so doing, the osmolalities of both the solution
and cell contents are altered and the cell’s volume changes (  isotonic)
If steady state cell volume  (expands), the solution is hypotonic (lower osmotic
pressure)
If the cell  (shrinks), the solution is hypertonic (higher osmotic pressure)
– the tears have a higher osmolality than blood,  tears are hypertonic
Lau & Jones (1999) reported LCP osmolalities ranging from 219.67
milliOsmoles/kg (OPTI-FREE® EXPRESS®) to 291.67 (normal saline)
RETURN TO LECTURE
SOLUTION PROPERTIES
SURFACE TENSION (ST)
Nominal surface
Stronger mutual attraction between surface molecules
The greater the attraction, the greater is the ST
Weaker mutual attraction between all other molecules
Surface molecules
All other molecules
SOLUTION PROPERTIES
SURFACE TENSION (ST)
Unlike ‘inner’ molecules, surface molecules have no
fellow molecules to ‘reach out to’. Their interaction
with adjacent materials is material (both) dependent
Surface molecules (green dots) have
balanced lateral forces but a net
inward force trying to compress the
array of molecules below. The surface
can be thought of as a ‘taut skin’
The forces acting on a completely surrounded
molecule (red dot) are balanced. Therefore,
there is no net force affecting it
SOLUTION PROPERTIES
WETTING (A WETS B)
A
(Tears)
(Wetting Soln.)
(Cleaner)
(MPS)
STB
STB
W
ETTING
STA
W
STA
STLower
TI
ET NG
Surface of A
Surface of B
(CL)
(Cornea)
B
STHigher
SOLUTION PROPERTIES
SURFACE TENSION (ST)
•
•
•
•
•
•
•
•
•
Surface Tension: commonly  (sigma) used but ST also common
SI unit of ST is newton per metre (N/m)
– for practical applications milliNewton/m common (mN/m)
For a substance to wet another, its ST must be LOWER than the target
STCornea 67.5 to 72 mN/m (Glasgow et al., 1999)
STTears 42 to 71.5 mN/m (Zhao & Wollmer, 1998, Nagyová & Tiffany, 1999)
STPMMA 32 to 49 mN/m (Rankin & Trager, 1970, Goudeau et al., 2000, Zagari et al., 2004)
STWater 72.8 mN/m at 20°C (sometimes 72.8 dynes/cm – not SI units)
STLCPs 34.89 mN/m (OPTI-FREE® EXPRESS®) to 77.13 (AOSept® before
neutralization, 71.54 after) (Lau & Jones (1999)
– this data suggests that OPTI-FREE® EXPRESS® should be able to wet many
CLs well because of its low ST
STPTFE (Teflon™) 18 mN/m (PolyTetraFluoroEthylene [PTFE]) – this low ST explains
why few substances are able to wet, coat, or form a film on PTFE
RETURN TO LECTURE
SOLUTION PROPERTIES
USE-BY (EXPIRY) DATING
•
•
•
Expiry/Use-By Dates: significant issue & should not be ignored
All regulatory authorities require indication of how long unopened product remains safe to
use - expiry date affixed to indicate this
Date usually based on laboratory test results and/or real-time experience that demonstrate t
product meets its claims, & remain sterile & safe
– date usually conservative estimate (often 18 – 36 months from manufacture)
– date depends on:
• product components & their inherent stabilities
• ability of buffer system (if any) to maintain solution pH at intended levels
• product formulation. Generally, dilute solutions have shorter working life &
stabilizers or ingredient ‘protectors’ may be required to extend it
• Packaging form & packaging material (e.g. light-excluding materials, materials that
have little or no affinity for product components)
• Storage conditions. Rule-of-thumb: temperature  10°C   2X
decay/decomposition/deterioration – worst-case storage conditions usually
stipulated to address this issue, e.g. Store below 30° C. Refrigeration [but not
freezing] may slow these processes but prohibition of refrigeration or freezing may
be necessary because solution components may come out of solution rendering
product less effective or even unsafe
SOLUTION PROPERTIES
EXPIRED BUT OPENED PRODUCT
While an expired but sealed/unopened product may be sterile, its safety and
efficacy can no longer be guaranteed or assumed, and its use should be
avoided
Legally, the supply of a short-dated (opening date plus the discard-after period
puts use of the product beyond its expiry date), or expired product to a CL
wearer is imprudent.
If an adverse clinical event results from either of the above, a legal defence of
the ‘sale’ or action would be difficult to mount. Such actions should be
regarded as ‘false economies’ with potentially disastrous outcomes
SOLUTION PROPERTIES
DISCARD-AFTER PERIODS
•
Discard-After periods: based on expectations of how LCP will be used in real-world.
Endeavour to account for:
–
likely exposure to ocular pathogens (from fingers, CLs, eyes, atmosphere [smaller nozzles reduce
exposure])
–
accidental exposure of dispensing nozzle to deleterious entities
–
ability of preservation system to cope with microbial exposure (preservatives/disinfectants are
usually altered irreversibly by interacting with micro-organisms, i.e. their concentration [and therefore
product’s efficacy] declines as result of successful antimicrobial action)
–
stability of product after opening ( access to atmospheric oxygen & contaminants)
–
margin of safety to be added (leaning towards worst-case scenario rather than ideal)
•
Discard-After information may be changed after product release (usually  ) should real-time experience
demonstrate that longer periods still safe
•
Unless LCP is self-preserving, e.g. it has significant alcohol content, preservative-free or unpreserved
products have Discard-After period of virtually zero, i.e. open, use, & discard almost immediately (or at
least after less than 1 to 2 hours, assuming ideal circumstances). This level of caution applies equally to
single-dose products as well as to bulk unpreserved products such as saline. The difficulty with bulk
products is the substantial volume that remains after their initial use - for many, the temptation to ‘keep it’
proves too great
•
With LCPs in general, if in doubt, throw them out!
RETURN TO LECTURE
SOLUTION PROPERTIES
INCOMPATIBILITIES
•
With mature LCP market, instances of true solution incompatibilities are relatively few provided products not misapplied,
e.g. GP lens products, especially cleaners, applied to SCLs
•
Also keeping incompatibility rates low is the division of many LCPs into just a few chemical families, principally the PHXs,
the PQ-1s, & the hydrogen peroxides. With catalytic disk-based systems, ensure that the catalyst is not ‘poisoned’ by, or
coated with, incompatible products. Paradoxically, should the disc’s effectiveness , the disinfection efficacy of the system
as a whole  (slower neutralization). Eventually, level of residual peroxide exceeds wearer’s tolerance & discomfort or
stinging will be reported
•
Difficulties occur with effervescent peroxide systems (most current products), especially if frothing occurs in case because
of introduced surfactants or enzymatic tablets. By a process of ‘froth flotation’, contaminants including viable microorganisms can gain access to the inside roof (ceiling) of the case where they can reside beyond reach of the disinfectant.
In this way, disinfection may be incomplete & recontamination can occur. To address this issue, wearers should be
instructed to shake their lens case vertically immediately after filling it with fresh peroxide so that the roof is bathed in, and
impacted by, full-strength peroxide
•
Most LCP incompatibilities are researched in the laboratory of the real world by users. Often this is a result of:
–
non-compliance
–
being induced into changing LCPs without adequate knowledge by:
–
•
an apparently better ‘deal’
•
a well-meaning friend or a misguided professional
•
the perception that an alternative is ‘better’
it is impractical to perform the laboratory research necessary to check all possible LCP (& CL types) combinations
SOLUTION PROPERTIES
INCOMPATIBILITIES
•
Additional aspects include:
–
if users compliant with the instructions given, problem would never arise
–
frequent release of new or revised products means education task is perpetual
–
existence of four FDA groups of hydrogels, the SiH category, & GP CLs complicates situation further
–
it can be difficult for some manufacturers to remain objective about their own products
–
other than manufacturers, who else has the technology and/or resources to undertake the task of LCP testing?
•
Nicolson (in Rakow, 1988) suggested that mixing preservatives of opposite charge be avoided, e.g. CHX, PHX, or PQ-1 (all
positively charged) should not be mixed with products containing sorbic acid (negatively charged). While Sibley
recommended against mixing any of the chemical SCL disinfection system, it could be argued that the situation is
somewhat simpler now (fewer basic chemistries) However, in the absence of specific research, caution required
•
If CL soaked in CHX is transferred to 3% hydrogen peroxide solution, the CHX is oxidized to a fine black precipitate
(Rakow, 1988). Sibley (in Rakow, 1988) reported lens discolouration possible with many different solutions if CLs soaked in
them were later transferred to peroxide. Discolouration due to internal precipitation of various chemicals. Discolourations
reported include: pink, yellow, brown, black, or purple
•
Stone (in Rakow, 1988) warned about interchanging neutralizers from the various peroxide solutions. Generally, with the
exception of AOSept® solution (and derivatives that all have a near normal pH and are almost isotonic) most Part 1
solutions (hydrogen peroxide) are interchangeable because they are usually of high quality (often ‘semiconductor grade’),
are well stabilized at 3%, have a low pH (often 3-4), with very low osmolality. Stone and Sibley warned against using
peroxide neutralizers in cases fitted with catalytic discs
•
Generally, inadvisable to soak CLs in CL cleaners because they are not intended for prolonged contact with CLs.
Prolonged exposure to cleaners such as MIRAFLOW ® (high isopropyl alcohol content) should be avoided especially if the
lenses are GPs
•
GP LCPs containing BAK must not be used on Hy or SiHy CLs
RETURN TO LECTURE
PRESERVATIVES
BAK
H
C
H
H
C
H
H
H
C8to C18
H
H
+
C
C
N
H
H
–
Cl
H
H
C
H
Benzene
Ring
Benzalkonium Chloride
CAS RN: 8001-54-5
• Benzalkonium chloride (BAK)
• Quaternary ammonium compound
• Mixture of alkyldimethylbenzylammonium
chlorides (ADBACs) of various even-numbered
alkyl (-CH2-) chain lengths
• Cationic (+ve) surfactant
• +ve charged, hydrophilic, benzene-ring ‘end’
binds to CLs & presents its hydrophobic tail
(C8 to C18 hydrocarbon) to the world
• Used ONLY in some GP LCPs
• not used in soaking solutions
• most modern LCPs do not use BAK
• Alters cell permeability  loss of cytoplasm
• Long-term usage can   CL wettability
• Binds well to hydrogel CLs – main reason GP
LCPs should not be used on SCLs (Hy & SiHy)
RETURN TO LECTURE
DISINFECTANTS
Optical (CL) grade peroxide is usually:
• 3% concentration (0.6% has been used)
• Diluted from concentrated, high-grade stock
• diluent: purified, deionized water
• Stabilized  long life &  decomposition
• stabilizers used include sodium stannate/sodium nitrate or
organophosphonates e.g. the Dequest series from thermPhos
International
• Formulated to have low (3-4) or a high (6.8) pH using phosphate
buffer system
• Can be formulated to be approximately isotonic (AOSept &
derivatives)
IUPAC Name: Dihydrogen Dioxide
DISINFECTANTS
PEROXIDE STABILIZER
O
O
HO
HO
P
HO
P
C
N
C
C
HO
HO
C
P
O
HO
C
O
C
N
P
N
C
C
OH
C
OH
OH
P
OH
O
DTPMP (Dequest 2060®)
CAS: 15827-60-8
DTPMP or diethylenetriamine penta(methylene phosphonic acid)
DTPMP: used as hydrogen peroxide stabilizer
RETURN TO LECTURE
DISINFECTANTS
BIGUANIDES
DISINFECTANTS
BIGUANIDES continued...
RETURN TO LECTURE
DISINFECTANTS
POLYQUATERNIUM-1
PolyQuaternium-1
RETURN TO LECTURE
MyristAmidoPropyl Dimethyl amine
DISINFECTANTS
ALCOHOLS
H
H
H
C
H
C
OH
H
Isopropyl alcohol [USAN]
CAS : 67-63-0
Ethanol
Alcohol [USP]
CAS : 64-17-5
• Modes of Action:
RETURN TO LECTURE
DISINFECTANTS
OTHERS
O
Cl
O
CHLORINE DIOXIDE
CAS: 10049-04-4
• Sodium chlorite (NaClO2) & H2O2 (trace amount [100 ppm] as stabilizer)
microbial
ClO2 = chlorine dioxide & ClO2– = chlorite ion
– basically, ClOAcidic

ClO2–
2components
– NaClO2 Na+ + ClO2–  ClO2 (an unstable but effective disinfectant)
NaClO2 = sodium chlorite
– 4NaClO2 Light
 2NaCl + O2 + 2NaClO3
NaClO3 = sodium chlorate
RETURN TO LECTURE
DISINFECTANTS
EXCIPIENTS: EDTAs
EthyleneDiamine Tetraacetic Acid
or
Edetic Acid
Only differences
Disodium EDTA
or
Edetate disodium
or
Edetate sodium
(sodium salt of EDTA)
RETURN TO LECTURE
CAS REGISTRY NUMBERS
Chemical Abstract Service (CAS) Registry Number: widely used system of identifying
chemical entities uniquely. CAS is division of American Chemical Society that assigns a
copyrighted identifying number to chemicals described in the literature. To date, >56 million
compounds have been assigned CAS numbers (CAS #, CAS RN, or simply CAS:), new
numbers being issued at a rate of about 12,000 each day (visit: http://www.cas.org/). An
expressed aim of the system is to identify entities that are identical but bear different names
or trade names, i.e. to counter marketing & advertising initiatives
CAS identifier consists of three clusters of numbers separated by hyphens, e.g. water is CAS:
7732-18-5. ‘Real’ data however is represented by centre (always two digits) & left clusters (a
variable # of up to 7 digits ) only. The right number (least significant bit, always a single digit)
is modulo 10 checksum digit to confirm internal consistency of the ‘real’ data (two left
clusters)
CAS numbers not systematic or categorized in any way, e.g. they are not a sequence,
1234-56-6 is a valid but unused CAS RN, similarly, 1234567-89-5 is as yet unused but
structurally, is also valid. Generally, lower CASRNs (left cluster) imply earlier Registry entry.
Few manufacturers are forthcoming with the CAS #s of their LCP ingredients
RETURN TO LECTURE
CURRENT LCP MARKET
The following slides contain the names of lens care products (LCPs)
gleaned from conferences & exhibitions, current journals, the internet,
company information, & knowledgeable IACLE members & staff
It is impossible to ascertain & then list all LCPs available worldwide.
To compound the problem, there are some LCPs sold under different
names, packages, labelling, etc. into different markets, sometimes by
the same company, at other times by local distributors/importers
Ultimately, this list can be neither complete nor current because
of the dynamics of a vigorous world marketplace for LCPs
You are invited to contribute to this list by way
of feedback on unlisted products, discontinued
products, & of course, new products
SURFACTANT CLEANERS
GP (DAILY)
Cleaners for GP CLS
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•
•
Cleaners for GP CLS
Alcon OPTI-FREE SupraClens
• EYEYE Crystal Cleaner
Alcon Opti-Clean II Daily Cleaner
• Lobob® Optimum Extra Strength Cleaner
Alcon OPTI-FREE Daily Cleaner
• Lobob® Sterile Cleaning Solution
Alcon Unique pH (limited channels)
• Menicon Spray & Clean
®
Alcon POLYCLENS II Daily Cleaner
• Optikem Intn’l Sereine® Contact Lens Cleaner
AMO AMO Total Care Cleaner
• Piiloset DAILY CLEANER
AVIZOR GP Cleaner
• Purahard Cleaner
AVIZOR Cleaning Drops
• Sauflon delta cleaner
Boston® Cleaner
Boston® Advance Lens Cleaner
Some products appear in both
Boston® Cleaner - Original Formula
GP and Hy & SiHy lists, i.e. they
contopharma i-clean! (Miraflow clone?)
are ‘universal’ & are suitable for
contopharma GPHCL Cleaner
use on GP, Hy, & SiHy CLs
CIBA Vision Miraflow Cleaner (avail.?)
CIBA Vision Miraflow Extra Strength Cleaner
N.B. Some products listed are
DISOP Durasol Cleaner
identical but are marketed under
different names in different
international markets
SURFACTANT CLEANERS
Hy & SiHy CLs (DAILY)
Cleaners for Hy & SiHy CLS
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Alcon OPTI-FREE Daily Cleaner
Alcon OPTI-FREE SupraClens
Alcon Opti-Clean II Daily Cleaner
AVIZOR Cleaning Drops
Bausch & Lomb Sensitive Eyes Daily Cleaner
CIBA Vision Miraflow Cleaner (avail.?)
CIBA Vision Miraflow Extra Strength Cleaner
Lobob Sof/Pro® Cleaner
SAUFLON PRESERVATIVE FREE DAILY CLEANER
Some products appear in both
GP and Hy & SiHy lists, i.e. they
are ‘universal’ & are suitable for
use on GP, Hy, & SiHy CLs
N.B. Some products listed are
identical but are marketed under
different names in different
international markets
SURFACTANT CLEANERS
CURRENT MARKET (PERIODIC)
Cleaners for GP CLS
Professional/Laboratory use ONLY
• Boston® Laboratory Lens Cleaner
• MeniCare Progent
• MeniLab Cleaner
Cleaners for Hy & SiHy CLS
• AVIZOR Lipid Clean for SiHy CLs
RETURN TO LECTURE
CURRENT LCP MARKET
The following slides contain the names of lens care products (LCPs)
gleaned from conferences & exhibitions, current journals, the internet,
company information, and knowledgeable IACLE members & staff
It is impossible to ascertain & then list ALL LCPs available worldwide.
To compound the problem further, there are some LCPs sold under
different names, packages, labelling, etc. into different markets,
sometimes by the same company, at other times by local
distributors/importers
Ultimately, this list can be neither complete nor current because
of the dynamics of a vigorous world marketplace for LCPs
You are invited to contribute to this list by way
of feedback on unlisted products, discontinued
products, and of course, new products
GP DISINFECTANTS
MPSs
• AMO Total Care 1 ALL-IN-ONE
• AMO Total Care C,D,S, & W Solution
• AMO Total Care Conditioner
• AVIZOR EVER clean Cleaning and Disinfecting Solution
• AVIZOR gp conditioner Wetting, Disinfecting, Storing, and Rinsing Solution
• AVIZOR gp multi All-in-one Solution
• Boston Advance Conditioning Solution
• Boston Simplus Multi-Action
• contopharma GPHCL MPS
• DISOP Durasol Conditioner
• DISOP Durasol Multipurpose Solution
GP DISINFECTANTS
MPSs (continued)
• Lobob® Hard Contact Lens Soaking Solution
• Lobob® Optimum Cleaning/Disinfecting/Storage Solution
• MeniCare Plus Multipurpose Solution
• Menicon SP Care
• Menicon Unique pH (formerly an Alcon product)
• Perfect Aqua Plus Conditioner
• Piiloset O2
• Purahard Conditioner
• Sauflon Comfort Vue Multipurpose Solution
• Sauflon delta plus Disinfecting, Soaking, and Wetting Solution
• SP&Eye Eyetec Multi-Purpose Solution
• Unicare ICN All in One Hard MPS
• Unicare ICN Green
• Vita Research Regard RGP
Hy & SiHy DISINFECTANTS
MPSs
• Alcon OPTI-FREE evermoist Multi-Purpose Disinfecting Solution
• Alcon OPTI-FREE Express MPDS
• Alcon OPTI-FREE RepleniSH MPDS
• AMO COMPLETE® Comfort Plus Solution
• AMO COMPLETE® Multi-Purpose Solution Easy Rub® Formula
• AMO RevitaLens OcuTec™ Multi-Purpose Disinfecting Solution
• AVIZOR Unica sensitive All-in-one Solution
• AVIZOR EVER clean Cleaning and Disinfecting Solution
• AVIZOR ALL clean SOFT
• AVIZOR ALL clean SOFT Unidose
• B&L renu fresh Multi-Purpose Solution
• B&L renu sensitive Multi-Purpose Solution
• B&L Bio true Multi-Purpose Solution
Hy & SiHy DISINFECTANTS
MPSs
• Chrome-X Image Care All-In-One Solution
• CIBA AQuify MPS
• CIBA Solocare Aqua Multi-Purpose Solution
• CL Works AQUAS Multi Multi Purpose Solution
• contopharma universal MPS
• contapharma simply one
• CooperVision Biomedics All-In-One
• CooperVision Frequency Multi-Purpose Solution
• CooperVision Options Multi-Function Solution
• DISOP Dúa Activa Multi-purpose Solution
• DISOP Dúa Elite Multi-purpose Solution
• DISOP Dúa Collection Multi-purpose Solution
• DREAMCON Beauty Multi purpose Solution
• Dueba NEO PLUS Multi-Purpose Solution
Hy & SiHy DISINFECTANTS
MPSs
• Emcol Hippia Multi Purpose Solution
• Eye-Tec Free-Sol Plus Multi Purpose Solution
• EYEYE Comfort 1-Step
• EYEYE All in One
• EYEYE Monosept
• Forcaza Fresh and Cool Deproteinized MPS
• Gaymed Labs Rinsol MPS
• GINZA Advance One Step Solution
• Grace Medicare OPTIC CLEAR Multipurpose Solution
• Helian 7 in 1 Multi-Purpose Solution
• HORIEN SUPER MOISTURIZING MULTI-PURPOSE SOLUTION
• i-WAY DR. CARE MPS (see (see Unique Visual Optiano MultiPlus MPS)
• I&G Optics EURO SOFT Multi-Purpose Solution
• Innovision eyegem Multi Purpose Solution
Hy & SiHy DISINFECTANTS
continued...
MPSs
• K&JC Dream Eye One CONTACT LENS Multi-Purpose Solution
• K&JC Dream Eye CONTACT LENS Multi-Purpose Solution
• Krystal Chemicals i eye care Plus Multi-Purpose Solution
• LensMam Seeshell Multi-purpose Solution Comfort Formula
• Opto-Pharm P2 Multi-Purpose Solution
• Orchidia Pharma PERFECT Care Multi-Purpose Solution
• P&G Latha AquaRefresh Sterile Multi-Purpose Solution
• pharmasafe PREMIUM GRADE MULTI PURPOSE SOLUTION
• pharmasafe MoistureRICH Multi-Purpose Solution
• Piiloset BioSoak all in one MPS
• Piiloset PRIMA MPS
• Polytouch ZERO-SEVEN Refreshing MPS
• Purahard PuraSept
• Purahard PuraSoft
Hy & SiHy DISINFECTANTS
continued...
MPSs
• Sauflon CyClean Multipurpose Solution
• Sauflon ALL IN ONE light Multipurpose Solution
• Sauflon Comfort Vue Multipurpose Solution
• Sauflon synergi
• SOLAREX Alpha MPS
• Unicare ICN All in One
• Unicare ICN Blue
• Unique Visual Optiano MultiPlus MPS (see i-WAY DR. CARE MPS)
• Vision Science Reviv Multipurpose Solution
• Vita Research Regard
• ZenBö VIZIONS Multi Purpose Solution
RETURN TO LECTURE
CURRENT LCP MARKET
The following slides contain the names of lens care products (LCPs)
gleaned from conferences & exhibitions, current journals, the internet,
company information, and knowledgeable IACLE members & staff
It is impossible to ascertain & then list ALL LCPs available worldwide.
To compound the problem further, there are some LCPs sold under
different names, packages, labelling, etc. into different markets,
sometimes by the same company, at other times by local
distributors/importers
Ultimately, this list can be neither complete nor current because
of the dynamics of a vigorous world marketplace for LCPs
You are invited to contribute to this list by way
of feedback on unlisted products, discontinued
products, and of course, new products
Hy & SiHy DISINFECTANTS
Hydrogen Peroxide Systems
• AMO Oxysept Disinfection System
• AMO Oxysept UltraCare Formula Peroxide Disinfection System
• AMO Oxysept 1-Step Disinfection System
• AMO Oxysept Comfort System
• AVIZOR Novoxy System
• AVIZOR Novoxy System unidose
• B&L renu EasySept Peroxide System
• CIBA AOSept Plus Disinfection System
• CIBA Clear Care
• CIBA DYNAEASY 4
• contopharma tab in one
Hy & SiHy DISINFECTANTS
continued...
Hydrogen Peroxide Systems
• DISOP Arión chronos
• DISOP Arión 1 & 2
• DISOP Arión DIsco
• Piiloset OXY SOFT System
• Sauflon Multi
• Titmus H2O2
• Unicare ICN Sept
RETURN TO LECTURE
CURRENT LCP MARKET
The following slides contain the names of lens care products (LCPs)
gleaned from conferences & exhibitions, current journals, the internet,
company information, and knowledgeable IACLE members & staff
It is impossible to ascertain & then list ALL LCPs available worldwide.
To compound the problem further, there are some LCPs sold under
different names, packages, labelling, etc. into different markets,
sometimes by the same company, at other times by local
distributors/importers
Ultimately, this list can be neither complete nor current because
of the dynamics of a vigorous world marketplace for LCPs
You are invited to contribute to this list by way
of feedback on unlisted products, discontinued
products, and of course, new products
GP WETTING SOLUTIONS
WETTING SOLUTIONS
• Lobob® Hard Contact Lens Wetting Solution
• Lobob® Optimum Wetting and Rewetting Drop
• Optikem Sereine Wetting and Soaking Solution
IN-EYE PREPARATIONS
• Alcon OPTI-FREE® Contacts Rewetting Drops
• Alcon OPTI-TEARS ®free Rewetting Drops
• Alcon Clens 100 Lens Drops
• AMO COMPLETE® Blink-N-Clean® Lens Drops
• AMO blink® Contacts Lubricating eye drops
• Boston® Rewetting Drops
• contopharma Moisturizing M
• EYEYE Hydraclair
• Sauflon COMFORT DROPS
Hy & SiHy WETTING SOLUTIONS
IN-EYE PREPARATIONS
•
AMO COMPLETE® Blink-N-Clean® Lens Drops
•
AMO blink® Contacts Lubricating eye drops
•
B&L renu MultiPlus Lubricating & Rewetting Drops
•
Chrome-X Comfort Shield Rewetting Drops
•
CIBA Aquify Long Lasting Comfort Drops
•
CIBA Clerz Rewetting Drops
•
contopharma lens & lid
•
contopharma drop & see
•
contopharma rewetting B
•
contopharma daily soft
•
DISOP NACLENS Comfort Drops
•
Sauflon COMFORT DROPS
RETURN TO LECTURE
CURRENT LCP MARKET
The following slides contain the names of lens care products (LCPs)
gleaned from conferences & exhibitions, current journals, the internet,
company information, and knowledgeable IACLE members & staff
It is impossible to ascertain & then list ALL LCPs available worldwide.
To compound the problem further, there are some LCPs sold under
different names, packages, labelling, etc. into different markets,
sometimes by the same company, at other times by local
distributors/importers
Ultimately, this list can be neither complete nor current because
of the dynamics of a vigorous world marketplace for LCPs
You are invited to contribute to this list by way
of feedback on unlisted products, discontinued
products, and of course, new products
GP CLs PROTEIN REMOVERS
Protein Removers for GP CLs
• AMO Total Care Protein Remover Tablets
• AMO Ultrazyme Universal Intensive Protein Cleaner
• AVIZOR enzyme
• Boston One-Step Enzyme
• DISOP Naclens Enzymes
• Menicon Progent
• Piiloset ENZYMATIC CLEANER
• Unicare ICN Protein Cleaning Tablets
Hy & SiHy PROTEIN REMOVERS
Protein Removers for Hy & SiHY CLs
• Abatron amiclair Protein Remover Tablets
• Alcon Clen-Zyme
• AMO Complete Protein Removing Tablets
• AMO Ultrazyme Universal Intensive Protein Cleaner
• AVIZOR enzyme
• CIBA Vision Unizyme
• DISOP Naclens Enzymes
• EyeSee Protein removal
• Piiloset ENZYMATIC CLEANER
• Sauflon trizyme Protein Remover Tablets
• Unicare ICN Protein Cleaning Tablets
RETURN TO LECTURE
5L3
End of appendices
REFERENCES
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Alizadeh H, Neelam S, Cavanagh HD (2009). Amoebicidal Activities of Alexidine Against 3 Pathogenic Strains of
Acanthamoeba. Eye & CL. 35(1): 1 – 5.
Boost et al. (2010). Do multipurpose contact lens disinfecting solutions work effectively against non-FDA/ISO
recommended strains of bacteria and fungi? Ophthal Physl Opt. 30: 12 – 19.
Callender MG et al. (1992). Effect of storage time with different lens care systems on in-office hydrogel trial lens
disinfection efficacy: A multi-center study. Optom Vis Sci. 69(9): 678 – 684.
Chalmers RL et al. (1989). The rate of in vivo neutralization of residual H2O2 from hydrogel lenses. CL Spectrum. 4(7): 21
– 26.
Chalmers RL, McNally JJ (1988). Ocular detection threshold for hydrogen peroxide: Drops vs. lenses. ICLC. 15(11): 351 –
357.
Collins MJ, Carney LG (1986). Patient compliance and its influence on contact lens wearing problems. Am J Optom Physl
Opt. 63(12): 952 – 956.
Davies DJG et al. (1990). Evaluations of the anti-Acanthamoebal activity of five contact lens disinfectants. ICLC. 17(1): 14
– 20.
Franklin VJ (1997). Cleaning efficacy of single-purpose surfactant cleaners and multi-purpose solutions. Cont Lens & Ant
Eye. 20(2): 63 – 68.
Ghormley N, Jones L (2006). Managing lipid deposition on silicone hydrogel lenses. CL Spectrum. 21(1): 21.
Glasgow BJ et al. (1999). Tear lipocalins: Potential lipid scavengers for the corneal surface. Invest Ophth Vis Sci. 40: 3100
– 3107.
Goudeau S et al. (2000). Modelling surface properties of linear amorphous polymers. Mat Res Soc Symp. 629: FF9.2.5.
Grant WM (1986). Toxicology of the eye. Charles C Thomas, Springfield.
Harris DC (1987). Quantitative Chemical Analysis. 2nd ed. WH Freeman and Company, New York.
REFERENCES
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Hong B-S et al. (1994). Cleaning capability of citrate-containing vs. non-citrate contact lens cleaning solutions: An in vitro
comparative study. ICLC. 21: 237 – 240.
Janoff LE (1990). Origin and development of hydrogen peroxide disinfection systems. CLAO J. 16(1): Suppl.: S36 – S42.
Lau J, Jones L (1999). Physical properties of multi-purpose contact lens solutions. Optom Vis Sci. 76(12)(Suppl.): 161.
Lever AM, Miller MJ (1999B). Reply: CLAO J. 25(2): 70.
López-Alemany A et al. (1997). Comparative study of pH for different salines and multi-purpose contact lens solutions.
Cont Lens & Ant Eye. 20(3): 91 – 95.
Lowe R et al. (1992). Comparative efficacy of contact lens disinfection solutions. CLAO J. 18(1): 34 – 40.
Luibinas J et al. (1987). Thermal disinfection of contact lenses. Clin Exp Optom. 70(1): 8 – 14.
Mahan BH (1975). University Chemistry. 3rd ed. Addison-Wesley Publishing Company, Reading.
McDonnell G, Russell AD (1999). Antiseptics and Disinfectants: Activity, Action, and Resistance. Clin Microbiol Rev.
12(1): 147 – 179.
McNally JJ (1990). Clinical aspects of topical application of dilute hydrogen peroxide solutions. CLAO J. 16(1): Suppl.:
S46 – S51.
Nagyová B, Tiffany JM (1999). Components responsible for the surface tension of human tears. Curr Eye Res. 19(1): 4 –
11.
Nichols JJ (2006). Deposition rates and lens care influence on galyfilcon A silicone hydrogel lenses. Optom Vis Sci 83(10):
751 – 757.
Parker J (1988). Interaction of contact lens materials and available lens care products. JBCLA. 11(4): 45 – 48.
Penley CA et al. (1985). Efficacy of hydrogen peroxide disinfection systems for soft contact lenses contaminated with fungi.
CLAO J. 11(1): 65 – 68.
Phillips AJ, Czigler B (1985). Polyclens (Opti-Clean) – A further study. Aust J Optom. 68(1): 36 – 39.
REFERENCES
•
•
•
•
•
•
•
•
•
•
Rakow PL (1988). Solution incompatibilities. CL Forum. 13(6): 41 – 46.
Rankin BF, Trager SF (1970). Surface wettability and the contact lens. J CL Soc Amer. 4(3): 5 - 7.
Reinhardt DJ et al. (1990). Rapid and simplified comparative evaluations of contact lens disinfecting solutions. ICLC.
17(1): 9 – 13.
Sweeney DF et al. (1992). Contamination of 500 ml bottles of unpreserved saline. Clin Exp Optom. 75(2): 67 – 75.
Sweeney DF et al. (1999). Incidence of contamination of preserved saline solutions during normal use. CLAO J. 25(3):
167 – 175.
Tonge S et al. (2001). Contact Lens Care: Part 5 – The design and development of wetting and multi-purpose solutions.
Optician 222(5812): 22 – 27.
Tonge S et al. (2001). Contact Lens Care: Part 6 – Comfort drops, artificial tears and dry-eye therapies. Optician
222(5817): 27 – 33.
Wilson LA (1986). Uni. of Md. 2nd annualcontact lens symposium: Contaminated lenses, solutions cited as causing
complications. CL Forum. 11(5): 50 – 51.
Zagari J et al. (2004). Small-core single-mode microstructured polymer optical fiber with large external diameter. Optics
Letters 29(8): 818 – 820.
Zhao J, Wollmer P (1998). Surface activity of tear fluid in normal subjects. Acta Ophthalmol Scand. 76(4): 438 – 441.
REFERENCES
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•
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URLs:
http://www.basfkorea.co.kr/02_products/04_finechemicals/document/cosmetic/tech/surfactants/down.asp?file=cremophorrh40.pdf
http://ec.europa.eu/health/scientific_committees/consumer_safety/opinions/sccnfp_opinions_97_04/sccp_out60_en.htm
http://en.wikipedia.org/wiki/Poloxamer_407
http://en.wikipedia.org/wiki/Poloxamer
http://en.wikipedia.org/wiki/Tyloxapol
5L1-150